FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DUNN, BK COGLIATI, T CULTRARO, CM BARNER, M SEGAL, S AF DUNN, BK COGLIATI, T CULTRARO, CM BARNER, M SEGAL, S TI REGULATION OF MURINE MAX (MYN) PARALLELS THE REGULATION OF C-MYC IN DIFFERENTIATING MURINE ERYTHROLEUKEMIA-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; RAS COTRANSFORMATION; NEOPLASTIC-CELLS; EXPRESSION; PROTEIN; GENE; ONCOGENE; GROWTH; FORMS AB Max is a basic region-helix-loop-helix-leucine zipper protein that consists of two major isoforms, p22 (long form, Max-L) and p21 (short form, Max-S). These proteins are encoded by two [the 1.9- and the predominant 2.3-kilobase (kb) forms] of the five alternatively spliced max mRNA species. We now demonstrate that N,N'-hexamethylene bisacetamide-mediated differentiation of murine erythroleukemia cells leads to a pattern of biphasic down-regulation of the 1.9- and the 2.3-kb myn (murine max) mRNAs that closely parallels that which occurs for myc mRNA. In contrast, the p22/Myn-L and p21/Myn-S protein isoforms down-regulate in monophasic fashion. Unlike the short-lived myc mRNA, the myn message is quite stable. However, its half-life of 3-6 h is still consistent with the biphasic down-regulation that accompanies differentiation. Furthermore, unlike myc, the overexpression of which prevents differentiation, elevated max levels merely delay differentiation. Coincident with this is a delay in the second decline of c-myc mRNA. In N,N'-hexamethylene bisacetamide-induced cells blocked from differentiating by overexpression of c-, N- or L-myc, myn mRNA expression is constitutive. These findings suggest that C1 USN,NCI,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 47 TC 16 Z9 16 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1994 VL 5 IS 8 BP 847 EP 854 PG 8 WC Cell Biology SC Cell Biology GA PB149 UT WOS:A1994PB14900006 PM 7986749 ER PT J AU EADER, LA GUSELLA, L DORMAN, L YOUNG, HA AF EADER, LA GUSELLA, L DORMAN, L YOUNG, HA TI INDUCTION OF MULTIPLE CYTOKINE GENE-EXPRESSION AND IRF-1 MESSENGER-RNA BY FLAVONE ACETIC-ACID IN A MURINE MACROPHAGE CELL-LINE SO CELLULAR IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN KINASE-C; RENAL-CANCER; PHASE-I; INTERFERON; TRANSCRIPTION; BETA; ENHANCEMENT; NSC-347-512; CARCINOMA AB Flavone-8-acetic (FAA) acid is a potential chemotherapeutic agent that has demonstrated strong immunomodulatory activity in murine model systems. The immunomodulatory activity of this drug in murine systems has been linked to its ability to rapidly induce cytokine gene expression in vivo and in mouse splenocytes ex vivo. We have now developed a tissue culture model for studying the molecular basis of induction of cytokine expression by FAA. Using the mouse macrophage cell line, ANA-1, we can demonstrate the direct induction of interferon beta (IFN beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), and interferon response factor-1 (IRF-1) mRNA expression following treatment with FAA. Furthermore, the induction of the IFN beta mRNA can occur in the absence of new protein synthesis. Nuclear run-on experiments indicate that at least part of the induction of IFN beta, IL-6, and TNF alpha mRNA occurs at the transcriptional level while the increase in IRF-1 mRNA appears largely post-transcriptional or due to the production of IFN beta protein. Additionally, experiments using agents that interfere with second messengers demonstrate that activation of the protein kinase C pathway is possibly involved in FAA gene induction. The use of this tissue culture model system should lead to a more complete understanding of the mechanisms involved in FAA-induced gene expression and help determine why this drug is inactive on human cells. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 30 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG PY 1994 VL 157 IS 1 BP 211 EP 222 DI 10.1006/cimm.1994.1217 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NZ093 UT WOS:A1994NZ09300018 PM 8039245 ER PT J AU BERMAN, CM RASMUSSEN, KLR SUOMI, SJ AF BERMAN, CM RASMUSSEN, KLR SUOMI, SJ TI RESPONSES OF FREE-RANGING RHESUS-MONKEYS TO A NATURAL FORM OF SOCIAL SEPARATION .1. PARALLELS WITH MOTHER-INFANT SEPARATION IN CAPTIVITY SO CHILD DEVELOPMENT LA English DT Article ID CAYO-SANTIAGO; MACAQUES; OVULATION; BEHAVIOR; CONFLICT; MULATTA AB Observations of 23 free-ranging rhesus monkey infants on Cayo Santiago, Puerto Rico, indicated that mothers' first postpartum estrous periods were marked by large increases in the amount of time infants were separated from their mothers, by disturbances in mother-infant relationships, and by increases in infant distress behavior. When their mothers resumed mating, most infants showed signs of agitation; a few briefly showed indications of depression. Male infants responded to their mothers' resumption of mating by playing more, whereas females engaged in less play and more allogrooming. The results suggest (a) that basic parallels exist between the behavioral responses of rhesus infants to their mothers' resumption of mating in the field and to forcible separation from their mothers in captivity and (b) that early separation experiences may play a role in the normal development or manifestation of sex differences in behavior. C1 NICHHD,BETHESDA,MD 20892. RP BERMAN, CM (reprint author), SUNY BUFFALO,DEPT ANTHROPOL,BUFFALO,NY 14261, USA. NR 53 TC 30 Z9 30 U1 2 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD AUG PY 1994 VL 65 IS 4 BP 1028 EP 1041 PG 14 WC Psychology, Educational; Psychology, Developmental SC Psychology GA PE841 UT WOS:A1994PE84100005 PM 7956463 ER PT J AU LENFANT, C AF LENFANT, C TI NEW HORIZONS SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 648 EP 648 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300002 PM 8044932 ER PT J AU GILLIGAN, DM BADAR, DM PANZA, JA QUYYUMI, AA CANNON, RO AF GILLIGAN, DM BADAR, DM PANZA, JA QUYYUMI, AA CANNON, RO TI ACUTE VASCULAR EFFECTS OF ESTROGEN IN POSTMENOPAUSAL WOMEN SO CIRCULATION LA English DT Article DE HORMONES; VASODILATION; ENDOTHELIUM; ENDOTHELIUM-DERIVED FACTORS; MUSCLE, SMOOTH ID ATHEROSCLEROTIC CORONARY-ARTERIES; NITRIC-OXIDE; ENDOTHELIAL-CELLS; ESSENTIAL-HYPERTENSION; INDUCED SENSITIZATION; UTERINE ARTERY; HEART-DISEASE; GUINEA-PIG; L-ARGININE; ACETYLCHOLINE AB Background Although hormone replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanisms that mediate this apparent benefit are unclear. Because improvement in vasomotor function may represent one of the beneficial effects of estrogen administration, we investigated the acute effects of physiological levels of estrogen on the vascular responses of estrogen-deficient postmenopausal women. Methods and Results The study included 40 postmenopausal women 60+/-8 years old (mean+/-SD), 20 of whom had one or more conditions associated with vascular dysfunction (hypertension, hypercholesterolemia, diabetes, or coronary artery disease). The forearm vascular responses to the endothelium-dependent vasodilator acetylcholine were studied before and during infusion of 17 beta-estradiol into the ipsilateral brachial artery. In 31 subjects, the effect of estradiol on the responses to the endothelium independent vasodilator sodium nitroprusside was also studied. Women with risk factors for vascular dysfunction had significantly reduced vasodilator responses to acetylcholine (P=.01) and to sodium nitroprusside (P<.001) compared with healthy subjects. Intra-arterial infusion of 17 beta-estradiol increased the forearm venous estradiol concentration from 16+/-10 to 318+/-188 pg/mL, levels typical of reproductive-age women at midcycle, but caused no vasodilation. However, estradiol potentiated the forearm vasodilation induced by acetylcholine by 18+/-30% (P<.001) in women with risk factors for vascular dysfunction and by 14+/-23% (P=.03) in healthy women. Estradiol also potentiated the forearm vasodilation induced by sodium nitroprusside in women with risk factors for vascular dysfunction by 14+/-21% (P<.001) but not in healthy women. Conclusions Physiological levels of 17 beta-estradiol selectively potentiate endothelium-dependent vasodilation in healthy postmenopausal women and potentiate both endothelium-ependent and endothelium-independent vasodilation in postmenopausal women with risk factors for atherosclerosis and evidence of impaired vascular function. These vascular effects may be partly responsible for the long-term benefit of estrogen therapy on cardiovascular events in postmenopausal women. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 33 TC 468 Z9 472 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 786 EP 791 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300021 PM 8044949 ER PT J AU TSUJI, H VENDITTI, FJ MANDERS, ES EVANS, JC LARSON, MG FELDMAN, CL LEVY, D AF TSUJI, H VENDITTI, FJ MANDERS, ES EVANS, JC LARSON, MG FELDMAN, CL LEVY, D TI REDUCED HEART-RATE-VARIABILITY AND MORTALITY RISK IN AN ELDERLY COHORT - THE FRAMINGHAM HEART-STUDY SO CIRCULATION LA English DT Article DE ELECTROCARDIOGRAPHY; EPIDEMIOLOGY; HEART RATE; MORTALITY ID FREQUENCY-DOMAIN MEASURES; RATE SPECTRAL-ANALYSIS; MYOCARDIAL-INFARCTION; PERIOD VARIABILITY; COMPONENTS; SEVERITY; DISEASE AB Background The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population. Methods and Results The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats >10% of total beats, <1 hour of recording time, processed time <50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/-SD) of 72+/-6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are >50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P<.0001), low-frequency power (P<.0001), high-frequency power (P=.0014), total power (P<.0001), and the standard deviation of total normal RR intervals (P=.0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P<.0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09). Conclusions The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. LAHEY CLIN MED CTR,BURLINGTON,MA 01803. NHLBI,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DIV EPIDEMIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA 02118. NR 29 TC 558 Z9 580 U1 3 U2 14 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 878 EP 883 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300033 PM 8044959 ER PT J AU FLUGELMAN, M EPSTEIN, SE AF FLUGELMAN, M EPSTEIN, SE TI AN ALTERNATIVE PATHOPHYSIOLOGICAL MECHANISM FOR UNSTABLE ANGINA - REPLY SO CIRCULATION LA English DT Letter RP FLUGELMAN, M (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG PY 1994 VL 90 IS 2 BP 1112 EP 1113 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA963 UT WOS:A1994PA96300072 ER PT J AU BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ AF BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ TI EFFECTS OF IPRATROPIUM BROMIDE ON BRADYKININ NASAL PROVOCATION IN CHRONIC ALLERGIC RHINITIS SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article ID PLASMA-PROTEIN LEAKAGE; MUCOSA; CAPSAICIN; SECRETION; HISTAMINE; INVITRO; RELEASE; INVIVO; LUNG AB Bradykinin (BK) induces albumin exudation and glandular secretion in chronic allergic rhinitis subjects. Since bradykinin may stimulate nociceptive sensory nerves, neural reflex arcs could contribute to the secretion process. Six chronic allergic rhinitis subjects received 1000 nm bradykinin by unilateral nasal provocation using the method of Raphael et al. This dose induces optimal contralateral glandular secretion. Ipratropium bromide (80 mu g) or saline were applied topically before the challenges. Total protein, albumin, glycoconjugate, and lysozyme were measured in lavage fluids. On the ipsilateral side, bradykinin induced significant total protein, glycoconjugate, and albumin secretion. None of these were affected by ipratropium. On the contralateral side, total protein and glycoconjugates were increased by bradykinin, while albumin and lysozyme were not significantly affected. Ipratropium bromide completely ablated total protein and glycoconjugate secretion on the contralateral side indicating that cholinergic reflexes mediated the glandular secretion. In chronic allergic rhinitis, bradykinin directly stimulated albumin secretion, but also stimulates nociceptive neuron-parasympathetic nerve reflexes to induce glandular secretion. The reflex loop was apparent on the contralateral side to the unilateral bradykinin challenge. This loop induced mucoglycoconjugate, but not serous cell, secretion in chronic allergic rhinitis subjects and can be inhibited by iptratropium bromide. C1 NIAID, CLIN INVEST LAB, ALLERG DIS SECT, BETHESDA, MD 20892 USA. NATL HEART & LUNG INST, LONDON, ENGLAND. RP GEORGETOWN UNIV, DIV RHEUMATOL ALLERGY & IMMUNOL, GL-020 GORMAN BLDG, 3800 RESERVOIR RD, WASHINGTON, DC 20007 USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD AUG PY 1994 VL 24 IS 8 BP 724 EP 729 DI 10.1111/j.1365-2222.1994.tb00982.x PG 6 WC Allergy; Immunology SC Allergy; Immunology GA PB665 UT WOS:A1994PB66500004 PM 7982121 ER PT J AU SUDO, K MAEKAWA, M KANNO, T LI, SSL AKIZUKI, S MAGARA, T AF SUDO, K MAEKAWA, M KANNO, T LI, SSL AKIZUKI, S MAGARA, T TI PREMATURE TERMINATION MUTATIONS IN 2 PATIENTS WITH DEFICIENCY OF LACTATE-DEHYDROGENASE H(B)-SUBUNIT SO CLINICAL CHEMISTRY LA English DT Article DE ISOENZYMES; GENETICS; HEREDITARY VARIANTS; DNA CONFORMATION POLYMORPHISM ID GENETIC MUTATIONS; DNA; VARIANT; AMPLIFICATION; POLYMERASE AB Two patients with low lactate dehydrogenase (LD) activity were discovered during healthcare examinations and were found to be homozygous for LD-H (heart) subunit deficiency by electrophoretic isoenzyme analysis of serum and erythrocyte hemolysate. The molecular nature of the genetic mutations was characterized by amplification by the polymerase chain reaction and DNA sequencing. In one case, a single-base substitution (T-->G transversion) at codon 147 of the LD-H(B) gene resulted in a nonsense mutation; in the other case, a deletion of 2 base pairs had occurred at codon 139, resulting in a frameshift translation and premature termination. C1 HAMAMATSU UNIV SCH MED, DEPT LAB MED, HAMAMATSU, SHIZUOKA 43131, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP SUDO, K (reprint author), JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, 4-11-1 IZUMI HONCHO, KOMAE, TOKYO 201, JAPAN. NR 20 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 1994 VL 40 IS 8 BP 1567 EP 1570 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PA073 UT WOS:A1994PA07300017 PM 8044998 ER PT J AU PLOTZ, PH MOUTSOPOULOS, HM AF PLOTZ, PH MOUTSOPOULOS, HM TI SSYMPOSIUM-IN-WRITING - INTRODUCTION SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Editorial Material C1 NATL TECH UNIV ATHENS,SCH MED,DEPT PATHOPHYSIOL,ATHENS,GREECE. RP PLOTZ, PH (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,CONNECT TISSUE DIS SECT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD AUG PY 1994 VL 72 IS 2 BP 153 EP 154 DI 10.1006/clin.1994.1120 PG 2 WC Immunology; Pathology SC Immunology; Pathology GA PB324 UT WOS:A1994PB32400001 ER PT J AU PLOTZ, PH AF PLOTZ, PH TI REVERSE IMMUNOLOGY - THE LESSONS FROM MYOSITIS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT Symposium on Progress in Autoimmune Diseases, in Honor of Norman Talals 60th Birthday CY NOV 06, 1993 CL SAN ANTONIO, TX ID TRANSFER-RNA-SYNTHETASE; ANTI-DNA ANTIBODIES; REACTIVE T-CELLS; INFLAMMATORY MYOPATHIES; AUTOIMMUNE-DISEASE; MICE; PROTEIN; AUTOANTIBODIES; POLYMYOSITIS; AUTOANTIGEN RP PLOTZ, PH (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CONNECT TISSUE DIS SECT,BETHESDA,MD 20892, USA. NR 27 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD AUG PY 1994 VL 72 IS 2 BP 204 EP 207 DI 10.1006/clin.1994.1131 PG 4 WC Immunology; Pathology SC Immunology; Pathology GA PB324 UT WOS:A1994PB32400012 PM 8050194 ER PT J AU KWONCHUNG, KJ AF KWONCHUNG, KJ TI PHYLOGENETIC SPECTRUM OF FUNGI THAT ARE PATHOGENIC TO HUMANS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RIBOSOMAL-RNA SEQUENCES; PNEUMOCYSTIS-CARINII; DIHYDROFOLATE-REDUCTASE; GENE; EVOLUTION; EXPRESSION; KINGDOMS; HOMOLOGY; YEAST AB Recent phylogenetic studies based on ribosomal RNA sequences have confirmed that the organisms traditionally treated as fungi include those that have evolved from several different lines (multiphyletic organisms), as has been suspected. Even organisms causing disease in humans represent at least two evolutional lines. Pythium insidiosum and Prototheca species are both believed to have evolved from one line, while the rest of the pathogens have evolved from another line. P. insidiosum is more closely related to red algae and diatoms than to fungi. Prototheca species, as has been previously postulated, are closer to blue-green algae and plants than to fungi. Pythiosis and protothecosis, however, will still be dealt with by medical mycologists because of the morphological and in vivo staining characteristics of the causative organisms. Molecular genetic studies have revealed that Pneumocystis carinii can best be categorized as a fungus, although questions regarding its fungal status may remain unanswered until additional information becomes available on its life cycle, nuclear division, cell-wall chemistry, nutritional uptake pattern, and lysine biosynthetic pathway as well as the ultrastructural characteristics of its cellular components such as the Golgi complex. The phylogeny of the agents of lobomycosis and rhinosporidiosis, although they are treated as fungi, remains unknown. Although there is no in vitro culture system for Loboa loboi and Rhinosporidium seeberi at present, a molecular approach would allow us to reveal their phylogenetic relationship, and we can hope that such attempts are forthcoming. RP KWONCHUNG, KJ (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BLDG 10,11C 304,BETHESDA,MD 20892, USA. NR 37 TC 42 Z9 42 U1 0 U2 3 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 AUG PY 1994 VL 19 SU 1 BP S1 EP S7 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PC397 UT WOS:A1994PC39700001 PM 7948565 ER PT J AU ROSSE, RB ALIM, TN FAYMCCARTHY, M COLLINS, JP VOCCI, FJ LINDQUIST, T JENTGEN, C HESS, AL DEUTSCH, SI AF ROSSE, RB ALIM, TN FAYMCCARTHY, M COLLINS, JP VOCCI, FJ LINDQUIST, T JENTGEN, C HESS, AL DEUTSCH, SI TI NIMODIPINE PHARMACOTHERAPEUTIC ADJUVANT THERAPY FOR INPATIENT TREATMENT OF COCAINE DEPENDENCE SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE COCAINE; CRAVING; VOLTAGE-SENSITIVE CALCIUM CHANNEL BLOCKERS; NIMODIPINE; DOPAMINE ID CALCIUM-CHANNEL BLOCKERS; CARBAMAZEPINE; ANTAGONISTS; WITHDRAWAL; SCHIZOPHRENIA; PERFORMANCE; NIFEDIPINE; PREDICTOR; TOXICITY; DISORDER AB Recent preclinical studies suggest utility for voltage-sensitive calcium channel blockers (VSCCBs) in the treatment of cocaine addiction. The following double-blind placebo-controlled study examined the role of the VSCCB nimodipine in attenuating cocaine craving in 66 recently abstinent cocaine-dependent patients on an inpatient substance abuse treatment unit utilizing an intensive 12-step milieu-oriented psychosocial therapy. While the medication was well tolerated, the dose of nimodipine used in this study (90 mg q.d.) was not superior to placebo in reducing background or cue-induced cocaine craving over the 3 weeks of the study. There was the suggestion that nimodipine might attenuate the severity of some cocaine-induced brain deficits, as detected by evaluation of smooth pursuit eye movement function. A rationale for evaluating higher doses of nimodipine for the treatment of cocaine addiction is presented. As nimodipine might have anticraving and mood-stabilizing properties and cardio- and neuroprotective properties in the face of cocaine intoxication and might possibly even reverse some cocaine-induced brain deficits, further investigation of the role of nimodipine (and other VSCCBs) in cocaine addiction appears an attractive avenue of future medication development. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. HOWARD UNIV,CTR MED,DEPT PSYCHIAT,WASHINGTON,DC. NIDA,DIV MEDICAT DEV,ROCKVILLE,MD. VET AFFAIRS MED CTR,VA NIDA SUBST ABUSE RES UNIT,WASHINGTON,DC. NR 50 TC 13 Z9 13 U1 4 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD AUG PY 1994 VL 17 IS 4 BP 348 EP 358 DI 10.1097/00002826-199408000-00007 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA NY721 UT WOS:A1994NY72100007 PM 9316683 ER PT J AU ROSSE, RB COLLINS, JP FAYMCCARTHY, M ALIM, TN WYATT, RJ DEUTSCH, SI AF ROSSE, RB COLLINS, JP FAYMCCARTHY, M ALIM, TN WYATT, RJ DEUTSCH, SI TI PHENOMENOLOGICAL COMPARISON OF THE IDIOPATHIC PSYCHOSIS OF SCHIZOPHRENIA AND DRUG-INDUCED COCAINE AND PHENCYCLIDINE PSYCHOSES - A RETROSPECTIVE STUDY SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE COCAINE; PHENCYCLIDINE; SCHIZOPHRENIA; PSYCHOSIS; PHENOMENOLOGY ID INDUCED PARANOIA; SYMPTOMS; MODEL AB Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizophrenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., ''anti-stimulant'' versus ''anti-PCP'') might address different aspects of the positive symptom picture in schizophrenia. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. HOWARD UNIV,CTR MED,DEPT PSYCHIAT,WASHINGTON,DC. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 32 TC 39 Z9 39 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD AUG PY 1994 VL 17 IS 4 BP 359 EP 369 DI 10.1097/00002826-199408000-00008 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA NY721 UT WOS:A1994NY72100008 PM 9316684 ER PT J AU KLEINMAN, DV SWANGO, PA PINDBORG, JJ AF KLEINMAN, DV SWANGO, PA PINDBORG, JJ TI EPIDEMIOLOGY OF ORAL MUCOSAL LESIONS IN UNITED-STATES SCHOOLCHILDREN - 1986-87 SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE CHILDREN AND ADOLESCENTS; ORAL MUCOSAL LESIONS; PREVALENCE; TOBACCO USE ID SMOKELESS TOBACCO; CHILDREN; ASSOCIATION; POPULATION; PREVALENCE; ANOMALIES; TONGUE AB Oral mucosal lesion findings from a national multistage probability oral health survey of United States schoolchildren in kindergarten through grade 12 are reported. In the 1986-87 school year 39206 children aged 5-17 yr were examined by 14 dentists trained in standardized clinical diagnostic criteria for dental caries. periodontal conditions and oral mucosal lesions. In addition all children were asked whether or not they ever had ''cold sores.'' ''fever blisters,'' or ''canker sores'', and adolescents (grades 6-12) were questioned about their history of tobacco use. About 4% of the children had one or more oral mucosal lesions present at the time of the examination, while 33 and 37% reported a history of recurrent herpes labialis and recurrent aphthous ulcers, respectively. The most prevalent lesions clinically observed were recurrent aphthous ulcers (1.23%), recurrent herpes labialis (0.78), smokeless tobacco lesions (0.71), and geographic tongue (0.60). Differences in prevalence were analyzed by age, sex, race, metropolitan area, and geographic region. Almost 10% of 12-17-yr-olds reported current use of some type of tobacco product. In adolescents the current use of tobacco products had a marked effect on the prevalence of oral lesions. C1 UNIV COPENHAGEN,FAC HLTH SCI,DK-1168 COPENHAGEN,DENMARK. RP KLEINMAN, DV (reprint author), NIDR,BLDG 31,ROOM 2C39,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 75 Z9 80 U1 3 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD AUG PY 1994 VL 22 IS 4 BP 243 EP 253 PG 11 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA NY109 UT WOS:A1994NY10900007 PM 7924239 ER PT J AU WANG, C PAHL, JJ HOGUE, RE AF WANG, C PAHL, JJ HOGUE, RE TI A METHOD FOR CO-REGISTERING 3-DIMENSIONAL MULTIMODALITY BRAIN IMAGES SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE IMAGE CO-REGISTRATION; BRAIN IMAGING; SPECT; MR; MEDICAL IMAGE PROCESSING ID POSITRON EMISSION TOMOGRAPHY; ANATOMICAL LOCALIZATION; AUTOMATED-METHOD; MR IMAGES; SPECT; PET; ALIGNMENT; ATLAS; LINE AB A method has been developed for co-registering three-dimensional multi-modality images of the human brain. The interactive program allows users to specify the interhemispheric fissure plane in three dimensions by identifying the endpoints of the centerline within transaxial slices. Translations and rotations within transaxial and coronal planes are determined to align the interhemispheric fissure planes of the two image sets to be co-registered. After reslicing the two partially co-registered image volumes, the intercommissural lines are detected by using three internal landmarks. A transformation including translation and rotation in the sagittal plane finally co-registers the two image sets in three-dimensional space. Single photon emission computed tomography (SPECT) images and magnetic resonance (MR) images have been used to validate the method for co-registering three-dimensional functional and anatomic brain images. This new co-registration method requires neither special head positioning procedures nor external fiducial markers, thereby making it appropriate for the routine clinical practice. C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT PSYCHIAT & BEHAV SCI,OKLAHOMA CITY,OK 73190. RP WANG, C (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,ROOM 6S235,BETHESDA,MD 20892, USA. NR 26 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD AUG PY 1994 VL 44 IS 2 BP 131 EP 140 DI 10.1016/0169-2607(94)90094-9 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA PG704 UT WOS:A1994PG70400009 PM 7988116 ER PT J AU BROWN, RH LYNCH, M LEEF, D GUNSBY, J LOBER, K MOORE, K STEPKA, C VELATHOMAS, A GAASTERLAND, DE COYLE, E HUNDLEY, M ASHBURN, F VAYER, L MICHELITSCH, K LAUBER, S BURT, E RAE, A WEBER, PA DERICK, R MCKINNEY, K MOORE, D BAKER, ND KAPETANSKY, F LEHMAN, D GLOECKNER, B SHARF, LJ ROMANS, B SATTERWHITE, Y SIMMONS, L HARBIN, TS OZMENT, RR WRIGHT, J BUTLER, L LASALLE, J PERRY, M NUMMERDOR, D WILLE, L ECKEL, A SESSION, C MARTIN, A CYRLIN, MN FAZIO, R WILENSKY, JT LINDENMUTH, K NAIL, CA RATHBONE, D GATES, V TADELMAN, M SONTY, S HOPKINS, G HIGGINBOTHAM, EJ SCHOLES, G UVA, R PAPPAS, L FROHLICHSTEIN, D FIENE, J BERGSTROM, TJ LICHTER, PR STANDARDI, C ZIEHMSCOTT, J PAPIERNIAKDUBIEL, R POLLACKRUNDLE, C SKUTA, GL BEESON, C CREW, RP KRUSEKE, L MICHAEL, B DEDERIAN, J WICKER, D AARON, D BIRK, J VANHECK, T ALLEN, RC NEWMAN, SA NORLUND, JR FENDLEY, CK BERGHUIS, C CHISHOLM, J EVANS, C MURPHY, E SCHOTT, LJ FORNILI, R SCHWARTZ, AL WEISS, H WEHRLY, S PAPPAS, S ODEA, M BOECKL, A LOPEZ, P CARMODY, K MERCER, R MONKS, V VAWTER, K WITOL, CV CIRONE, M GURLEY, J REED, C BROWNING, J HARRIS, E KATZ, LJ SPAETH, GL WILSON, RP SAMUEL, F BLOCK, A KAO, S BEKERSHOFF, CC CAPRIOLI, J MILLER, E ROCHE, M GROTTOLE, G LEONE, A TRESSLER, C EDERER, F SULLIVAN, EK WAGNER, EL ENTLER, G BRADFORD, M TOMLIN, KL STINE, E LINDBLAD, AS KNOKE, JD DENEKAS, M SMITH, C VOSS, T MOWERY, RL LYNCH, G GOFF, F FURBERG, CD CONNETT, JE DAVIS, MD DUEKER, DK GREEN, SB HAMILTON, MP SCHNEIDERMAN, MA KASSOFF, A MORRIS, M PALMBERG, PF AF BROWN, RH LYNCH, M LEEF, D GUNSBY, J LOBER, K MOORE, K STEPKA, C VELATHOMAS, A GAASTERLAND, DE COYLE, E HUNDLEY, M ASHBURN, F VAYER, L MICHELITSCH, K LAUBER, S BURT, E RAE, A WEBER, PA DERICK, R MCKINNEY, K MOORE, D BAKER, ND KAPETANSKY, F LEHMAN, D GLOECKNER, B SHARF, LJ ROMANS, B SATTERWHITE, Y SIMMONS, L HARBIN, TS OZMENT, RR WRIGHT, J BUTLER, L LASALLE, J PERRY, M NUMMERDOR, D WILLE, L ECKEL, A SESSION, C MARTIN, A CYRLIN, MN FAZIO, R WILENSKY, JT LINDENMUTH, K NAIL, CA RATHBONE, D GATES, V TADELMAN, M SONTY, S HOPKINS, G HIGGINBOTHAM, EJ SCHOLES, G UVA, R PAPPAS, L FROHLICHSTEIN, D FIENE, J BERGSTROM, TJ LICHTER, PR STANDARDI, C ZIEHMSCOTT, J PAPIERNIAKDUBIEL, R POLLACKRUNDLE, C SKUTA, GL BEESON, C CREW, RP KRUSEKE, L MICHAEL, B DEDERIAN, J WICKER, D AARON, D BIRK, J VANHECK, T ALLEN, RC NEWMAN, SA NORLUND, JR FENDLEY, CK BERGHUIS, C CHISHOLM, J EVANS, C MURPHY, E SCHOTT, LJ FORNILI, R SCHWARTZ, AL WEISS, H WEHRLY, S PAPPAS, S ODEA, M BOECKL, A LOPEZ, P CARMODY, K MERCER, R MONKS, V VAWTER, K WITOL, CV CIRONE, M GURLEY, J REED, C BROWNING, J HARRIS, E KATZ, LJ SPAETH, GL WILSON, RP SAMUEL, F BLOCK, A KAO, S BEKERSHOFF, CC CAPRIOLI, J MILLER, E ROCHE, M GROTTOLE, G LEONE, A TRESSLER, C EDERER, F SULLIVAN, EK WAGNER, EL ENTLER, G BRADFORD, M TOMLIN, KL STINE, E LINDBLAD, AS KNOKE, JD DENEKAS, M SMITH, C VOSS, T MOWERY, RL LYNCH, G GOFF, F FURBERG, CD CONNETT, JE DAVIS, MD DUEKER, DK GREEN, SB HAMILTON, MP SCHNEIDERMAN, MA KASSOFF, A MORRIS, M PALMBERG, PF TI THE ADVANCED GLAUCOMA INTERVENTION STUDY (AGIS) .1. STUDY DESIGN AND METHODS AND BASE-LINE CHARACTERISTICS OF STUDY PATIENTS SO CONTROLLED CLINICAL TRIALS LA English DT Article DE CLINICAL TRIAL DESIGN; OPEN-ANGLE GLAUCOMA; LASER SURGERY; TRABECULECTOMY; VISUAL ACUITY; VISUAL FIELDS ID OPEN-ANGLE GLAUCOMA; CLINICAL RESEARCH; FOLLOW-UP; TRABECULECTOMY; MITOMYCIN AB Medical therapy has been the standard initial treatment for open-angle glaucoma. When some visual field has been lost and maximum tolerated and effective medical therapy does not succeed in controlling the disease, the patient is considered to have advanced glaucoma, and the first of a potential sequence of surgical treatments is usually indicated. Little is known about the long-term course and prognosis of advanced glaucoma or about the long-term effectiveness of sequential surgical treatments in controlling the disease and preventing vision loss and blindness. The Advanced Glaucoma Intervention Study was designed to study, in advanced glaucoma, the long-term clinical course and prognosis, and, in a randomized trial, the comparative outcomes of two sequences of surgical treatments. Toward these goals, 789 eyes in 591 patients were enrolled at 11 clinical centers between 1988 and 1992. Follow-up will continue until 1996. Eyes were randomly assigned to one of two sequences of surgical treatments. One sequence begins with argon laser trabeculoplasty (ALT), is followed by trabeculectomy, an incisional surgical filtering procedure, should ALT fail to control the disease, and by a second trabeculectomy should the first trabeculectomy fail. The other sequence begins with trabeculectomy, is followed by ALT should the trabeculectomy fail, and by a second trabeculectomy should ALT fail. The main outcome of interest is visual function (visual field and visual acuity). Other important outcomes are intraocular pressure, complications of surgery, time to treatment failure, and extent of need for additional medical therapy. We present in this paper the rationale, objectives, design and methods of the study, and the baseline characteristics of study patients and eyes. C1 EMMES CORP,POTOMAC,MD 20854. GEORGETOWN UNIV,DEPT OPHTHALMOL,WASHINGTON,DC. UNIV OPHTHALM CONSULTANTS RES & EDUC FDN,WASHINGTON,DC. EMORY UNIV,ATLANTA,GA 30322. OHIO STATE UNIV,COLUMBUS,OH 43210. PIEDMONT HOSP,ATLANTA,GA. SINAI HOSP DETROIT,SOUTHFIELD,MI. UNIV ILLINOIS,CHICAGO,IL. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV VIRGINIA,CHARLOTTESVILLE,VA. WASHINGTON HOSP CTR,CHEVY CHASE,MD. WILLS EYE HOSP & RES INST,PHILADELPHIA,PA. YALE UNIV,NEW HAVEN,CT. NATL EYE INST,WASHINGTON,DC. NR 32 TC 91 Z9 91 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1994 VL 15 IS 4 BP 299 EP 325 PG 27 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA PA969 UT WOS:A1994PA96900006 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI STONE-TOOL BONE-SURFACE MODIFICATION BY MONKEYS SO CURRENT ANTHROPOLOGY LA English DT Article ID PLIO-PLEISTOCENE HOMINIDS; NATIONAL-PARK; OLDUVAI-GORGE; CEBUS-APELLA; WILD CHIMPANZEES; CAPUCHIN; BEHAVIOR; TANZANIA; MEAT; APES RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,NATL INST HLTH ANIM CTR,POB 529,POOLESVILLE,MD 20837, USA. NR 26 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0011-3204 J9 CURR ANTHROPOL JI Curr. Anthropol. PD AUG-OCT PY 1994 VL 35 IS 4 BP 468 EP 470 DI 10.1086/204306 PG 3 WC Anthropology SC Anthropology GA PG430 UT WOS:A1994PG43000018 ER PT J AU DASTGHEIB, K HIKITA, N SREDNI, B ALBECK, M SREDNI, D NUSSENBLATT, RB CHAN, CC AF DASTGHEIB, K HIKITA, N SREDNI, B ALBECK, M SREDNI, D NUSSENBLATT, RB CHAN, CC TI OCULAR INFLAMMATION STIMULATED BY THE IMMUNOMODULATOR AS101 [AMMONIUM TRICHLORO(DIOXYETHELENE-O-O') TELLURATE] SO CURRENT EYE RESEARCH LA English DT Article DE AS101; IMMUNOMODULATOR; INTRAVITREAL INJECTION; INTERLEUKIN-6; OCULAR INFLAMMATION; RAT ID ASTA-Z 7557; INDUCER BRYOSTATIN; HUMAN-FIBROBLASTS; CANCER-PATIENTS; AS-101; INTERLEUKIN-6; MONOCYTES; CELLS; EXPRESSION; INTERFERON AB The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 mu g/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20814. BAR ILAN UNIV,CAIR INST,DEPT LIFE SCI,BAR ILAN,ISRAEL. BAR ILAN UNIV,DEPT INTERDISCIPLINARY,BAR ILAN,ISRAEL. NR 31 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD AUG PY 1994 VL 13 IS 8 BP 603 EP 610 DI 10.3109/02713689408999894 PG 8 WC Ophthalmology SC Ophthalmology GA PC876 UT WOS:A1994PC87600007 PM 7956313 ER PT J AU DONALDSON, JG KLAUSNER, RD AF DONALDSON, JG KLAUSNER, RD TI ARF - A KEY REGULATORY SWITCH IN MEMBRANE TRAFFIC AND ORGANELLE STRUCTURE SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTP-BINDING-PROTEIN; COP-COATED VESICLES; GOLGI MEMBRANES; BREFELDIN-A; BETA-COP; ENDOPLASMIC-RETICULUM; GUANINE-NUCLEOTIDE; PHOSPHOLIPASE-D; FACTOR-III AB The small GTP-binding protein ADP ribosylation factor (ARF) regulates, through a GTP cycle, the reversible binding of cytosolic coat proteins to Golgi membranes. By determining the binding and release of coat proteins from membranes, ARF controls the production and lifetime of coated-membrane structures. In the past year, studies suggesting a role for ARF in phospholipid metabolism have broadened our perspective on ARF function within the cell. RP DONALDSON, JG (reprint author), NICHHD,CELL BIOL & METAB BRANCH,9000 ROCKVILLE PIKE,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. NR 54 TC 235 Z9 238 U1 2 U2 4 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 AUG PY 1994 VL 6 IS 4 BP 527 EP 532 DI 10.1016/0955-0674(94)90072-8 PG 6 WC Cell Biology SC Cell Biology GA PA835 UT WOS:A1994PA83500006 PM 7986529 ER PT J AU PANTALEO, G FAUCI, AS AF PANTALEO, G FAUCI, AS TI TRACKING HIV DURING DISEASE PROGRESSION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-SYSTEM ACTIVATION; T-CELLS; INTERLEUKIN-2 RECEPTORS; TYPE-1 INFECTION; LYMPHOCYTES-T; LYMPH-NODES; AIDS; APOPTOSIS; DEATH AB Several recent advances have been made in the delineation of the multiple pathogenic mechanisms involved in the progression of HIV disease. Included among these are the virological and immunological events associated with primary infection and the delineation of the role of lymphoid organs. RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 46 TC 35 Z9 35 U1 0 U2 1 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 AUG PY 1994 VL 6 IS 4 BP 600 EP 604 DI 10.1016/0952-7915(94)90148-1 PG 5 WC Immunology SC Immunology GA PC330 UT WOS:A1994PC33000015 PM 7946049 ER PT J AU LEONARD, WJ AF LEONARD, WJ TI THE DEFECTIVE GENE IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY ENCODES A SHARED INTERLEUKIN RECEPTOR SUBUNIT - IMPLICATIONS FOR CYTOKINE PLEIOTROPY AND REDUNDANCY SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SIGNAL TRANSDUCER GP130; GAMMA-CHAIN; CHROMOSOME INACTIVATION; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; INHIBITION; CLONING; CELLS AB The interleukin-2 receptor plays a pivotal role in the regulation of the normal T cell immune response to foreign antigen. The IL-2 receptor gamma-chain is one component of this receptor, and is encoded by the gene that is defective in X-linked severe combined immunodeficiency. The clinical manifestations of this disease led to the hypothesis and subsequent confirmation that the gamma-chain was in fact a subunit shared by multiple cytokine receptors, including those for IL-2, IL-4, and IL-7. RP LEONARD, WJ (reprint author), NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 32 TC 47 Z9 48 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1994 VL 6 IS 4 BP 631 EP 635 DI 10.1016/0952-7915(94)90152-X PG 5 WC Immunology SC Immunology GA PC330 UT WOS:A1994PC33000019 PM 7946053 ER PT J AU KARP, JE MERZ, WG DICK, JD AF KARP, JE MERZ, WG DICK, JD TI MANAGEMENT OF INFECTIONS IN NEUTROPENIC PATIENTS - NEW OPPORTUNITIES AND EMERGING CHALLENGES SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Article AB The approach to infection management in the neutropenic host is being refined as new antimicrobial agents and strategies aimed at augmenting various components of host competence are entering the realm of clinical investigation. To this end, diverse hematopoietic growth factors are being tested for their abilities to enhance cellular and humoral host defenses directed against bacterial and, most recently, fungal infections in the hematopoietically compromised patient. Additional novel antifungal approaches include new vehicles for local and systemic amphotericin B administration, for example aerosolized and lipid-based preparations. These are designed to deliver higher concentrations of the drug to sites of active infection and, at the same time, to spare the host from the well documented amphotericin-B-related multiorgan toxicities. The emergence of resistant pathogens, exemplified by vancomycin-resistant enterococci, challenges the current therapeutic armamentarium and will be addressed only through the development of structurally and functionally novel antibodies. RP KARP, JE (reprint author), NCI,OFF DIRECTOR,9000 ROCKVILLE PIKE,BLDG 31,ROOM 11A29,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 1994 VL 7 IS 4 BP 430 EP 435 DI 10.1097/00001432-199408000-00003 PG 6 WC Infectious Diseases SC Infectious Diseases GA PC868 UT WOS:A1994PC86800003 ER PT J AU UDELSMAN, R HOLBROOK, NJ AF UDELSMAN, R HOLBROOK, NJ TI ENDOCRINE AND MOLECULAR RESPONSES TO SURGICAL STRESS SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; ACUTE PHASE RESPONSE; HEAT-SHOCK PROTEIN; NF-KAPPA-B; ANESTHETIZED CYNOMOLGUS MONKEY; SYMPATHETIC NERVOUS-SYSTEM; BETA-ADRENERGIC RECEPTORS; AGE-DEPENDENT RESPONSE; GLUCOCORTICOID RECEPTOR; MESSENGER-RNA C1 NIH,GERONTOL RECH INST,GENE EXPRESS & AGING,BETHESDA,MD 20892. RP UDELSMAN, R (reprint author), JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205, USA. NR 176 TC 18 Z9 18 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD AUG PY 1994 VL 31 IS 8 BP 655 EP 720 PG 66 WC Surgery SC Surgery GA PA387 UT WOS:A1994PA38700001 ER PT J AU COONROD, BA BETSCHART, J HARRIS, MI AF COONROD, BA BETSCHART, J HARRIS, MI TI FREQUENCY AND DETERMINANTS OF DIABETES PATIENT EDUCATION AMONG ADULTS IN THE US POPULATION SO DIABETES CARE LA English DT Article ID INTERVENTIONS; MELLITUS AB OBJECTIVE - To determine the proportion of adults with diabetes in the U.S. who have received diabetes patient education and to assess factors that determine whether patients receive this education. RESEARCH DESIGN AND METHODS - A questionnaire on diabetes was administered to a representative sample of 2,405 diabetic individuals greater than or equal to 18 years of age in the U.S. population. The questionnaire inquired about whether these individuals had ever attended a diabetes education class or program. Sociodemographic and clinical factors that may influence participation in patient education were also determined. RESULTS - Of all people with diabetes, 35.1% had attended a class or program about diabetes at some lime during the course of their disease, including 58.6% of individuals with insulin-dependent diabetes mellitus, 48.9% of insulin-treated individuals with non-insulin-dependent diabetes mellitus (NIDDM), and 23.7% of NIDDM individuals not treated with insulin. Younger age, black race, residence in the midwest region of the U.S., higher level of education, and presence of diabetes complications were consistently associated with having had diabetes education for people with NIDDM. Although increasing income was associated with patient education for NIDDM individuals not treated with insulin, it was not an independent determinant for insulin-treated NIDDM individuals. NIDDM individuals not treated with insulin who lived alone were more likely to have had patient education than those who did not live alone. Not having a diabetes physician or not visiting one in the past year was associated with a higher likelihood of patient education for non-insulin-treated NIDDM individuals. CONCLUSIONS - A large proportion of patients with diabetes has never received diabetes education. Patient education has been recognized for its contributions to reducing the morbidity and mortality of diabetes. Consequently, special attention should be directed to the subgroups of individuals, such as those not taking insulin, those with lower socioeconomic status, and those living outside urban areas, in which the frequency of diabetes patient education is particularly low. C1 NIDDKD,BETHESDA,MD 20892. BEAVER PA INC,MED CTR,BEAVER,PA. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA 15213. NR 14 TC 91 Z9 94 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1994 VL 17 IS 8 BP 852 EP 858 DI 10.2337/diacare.17.8.852 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NY359 UT WOS:A1994NY35900010 PM 7956630 ER PT J AU JAVITT, JC AIELLO, LP CHIANG, YP FERRIS, FL CANNER, JK GREENFIELD, S AF JAVITT, JC AIELLO, LP CHIANG, YP FERRIS, FL CANNER, JK GREENFIELD, S TI PREVENTIVE EYE CARE IN PEOPLE WITH DIABETES IS COST-SAVING TO THE FEDERAL-GOVERNMENT - IMPLICATIONS FOR HEALTH-CARE REFORM SO DIABETES CARE LA English DT Article ID TREATING RETINOPATHY; 4-YEAR INCIDENCE; DIAGNOSIS; MELLITUS; AGE; PHOTOCOAGULATION; PROGRESSION; PREVALENCE; SEVERITY; DISEASE AB OBJECTIVE - Diabetic retinopathy, which leads to macular edema and retinal neovascularization, is the leading cause of blindness among working-age Americans. Previous research has demonstrated significant cost savings associated with detection of eye disease in Americans with type I diabetes. However, detection and treatment of eye disease among those with type II diabetes was previously thought not to be test-saving. Our purpose was to estimate the current and potential federal savings resulting from the screening and treatment of retinopathy in patients with type II diabetes, based on recently available data concerning efficacy of treating both macular edema and neovascularization along with new data on federal budgetary costs of blindness. RESEARCH DESIGN AND METHODS - We used computer modeling, incorporating data from population-based epidemiological studies and multicenter clinical trials. Monte Carlo simulation was used, combined with sensitivity analysis and present value analysis of cost savings. RESULTS - Screening and treatment for eye disease in patients with type II diabetes generates annual savings of $247.9 million to the federal budget and 53,986 person-years of sight, even at current suboptimal (60%) levels of care. If all patients with type II diabetes receive recommended care, the predicted net savings (discounted at 5%) exceeds $472.1 million and 94,304 person-years of sight. Nearly all savings are associated with detection and treatment of diabetic macular edema. Enrolling each additional person with type II diabetes into currently recommended ophthalmological care results in an average net savings of $975/person, even if all costs of care are borne by the federal government. CONCLUSIONS - Our analysis indicates that prevention programs aimed at improving eye care for patients with diabetes not only reduce needless vision loss but also will provide a financial return on the investment of public funds. C1 JOHNS HOPKINS UNIV, WILMER OPHTHALMOL INST, BALTIMORE, MD 21218 USA. JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA 02215 USA. NEI, OFF BIOMETRY, BETHESDA, MD 20892 USA. TUFTS UNIV NEW ENGLAND MED CTR, INST HLTH, DIABET PORT PROJECT, BOSTON, MA 02111 USA. RP JAVITT, JC (reprint author), GEORGETOWN UNIV, MED CTR, CTR SIGHT, WORTHEN CTR EYE CARE RES, 3800 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. FU AHRQ HHS [P01-HS08005]; NEI NIH HHS [R21-EY07744, R0I-EYO8805] NR 52 TC 210 Z9 212 U1 0 U2 7 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 AUG PY 1994 VL 17 IS 8 BP 909 EP 917 DI 10.2337/diacare.17.8.909 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NY359 UT WOS:A1994NY35900023 PM 7956643 ER PT J AU GUERREMILLO, M QUON, MJ ESPOSITO, D TAYLOR, SI CUSHMAN, SW AF GUERREMILLO, M QUON, MJ ESPOSITO, D TAYLOR, SI CUSHMAN, SW TI THE TRANSCRIPTION FACTOR SP1 TRANSACTIVATES GLUT1 AND GLUT4 PROMOTERS IN RAT ADIPOSE-CELLS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,DIABET BRANCH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1994 VL 37 SU 1 BP A81 EP A81 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB881 UT WOS:A1994PB88100313 ER PT J AU OBROSOVA, I INOUE, J GREENTREE, W SATO, S RODRIGUEZ, L KADOR, PF AF OBROSOVA, I INOUE, J GREENTREE, W SATO, S RODRIGUEZ, L KADOR, PF TI EFFECT OF S-88-0773 ON DIABETIC CATARACT AND METABOLIC PARAMETERS IN LENS AND SCIATIC-NERVE SO DIABETOLOGIA LA English DT Meeting Abstract C1 NEI,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1994 VL 37 SU 1 BP A206 EP A206 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB881 UT WOS:A1994PB88100791 ER PT J AU DUH, FM LATIF, F WENG, YK GEIL, L MODI, W STACKHOUSE, T MATSUMURA, F DUAN, DR LINEHAN, WM LERMAN, MI GNARRA, JR AF DUH, FM LATIF, F WENG, YK GEIL, L MODI, W STACKHOUSE, T MATSUMURA, F DUAN, DR LINEHAN, WM LERMAN, MI GNARRA, JR TI CDNA CLONING AND EXPRESSION OF THE HUMAN HOMOLOG OF THE SEA-URCHIN FASCIN AND DROSOPHILA SINGED GENES WHICH ENCODES AN ACTIN-BUNDLING PROTEIN SO DNA AND CELL BIOLOGY LA English DT Article ID IDENTIFICATION; INTERLEUKIN-2; CELLS AB cDNA clones having extensive sequence identity with the sea urchin fascin and the Drosophila singed gene products were isolated from a human teratocarcinoma cDNA library. The human homolog, termed hsn, is a single-copy gene that was localized to human chromosome 7p22 by fluorescence in situ hybridization and is predicted to encode a 493-amino-acid product with a molecular mass of approximately 55,000. This protein would be similar in size to the fascin and singed proteins, as well as a previously described 55-kD actin-bundling protein that was purified from HeLa cells. Monoclonal antibodies directed against the 55-kD HeLa protein were reactive against a bacterially expressed hsn fusion protein, indicating that the hsn gene probably encodes the 55-kD protein. The hsn mRNA was variably expressed in all human tissues analyzed and was highly expressed in actively growing renal carcinoma cell lines and in activated, but not in resting, lymphocytes, suggesting a functional role for hsn in proliferation. The fascin family lacks homology with other characterized actin-binding proteins, and the high degree of evolutionary conservation of these proteins indicates a functional importance of their actin-bundling properties. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. RUTGERS STATE UNIV,DEPT MOLEC BIOL & BIOCHEM,PISCATAWAY,NJ 08855. NR 22 TC 70 Z9 78 U1 0 U2 8 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 1994 VL 13 IS 8 BP 821 EP 827 DI 10.1089/dna.1994.13.821 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA PE756 UT WOS:A1994PE75600004 PM 8068206 ER PT J AU KUPRASH, DV ALIMZHANOV, MB POKHOLOK, DK KOZLOV, SV NOVOBRANTSEVA, TI TURETSKAYA, RL NEDOSPASOV, SA AF KUPRASH, DV ALIMZHANOV, MB POKHOLOK, DK KOZLOV, SV NOVOBRANTSEVA, TI TURETSKAYA, RL NEDOSPASOV, SA TI CHARACTERIZATION OF GENETIC-LOCUS OF MURINE CHROMOSOME-17, CONTAINING 3 GENES OF TNF FAMILY, INCLUDING A NEW GENE FOR LYMPHOTOXIN-BETA SO DOKLADY AKADEMII NAUK LA Russian DT Article ID TUMOR-NECROSIS-FACTOR; TANDEM ARRANGEMENT; CELL-SURFACE; FACTOR-ALPHA; HUMAN GENOME; COMPLEX; MOUSE C1 NCI,FREDERICK,MD 21701. RP KUPRASH, DV (reprint author), VA ENGELGARDT MOLEC BIOL INST,MOSCOW,RUSSIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 15 TC 3 Z9 3 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0869-5652 J9 DOKL AKAD NAUK+ JI Dokl. Akad. Nauk PD AUG PY 1994 VL 337 IS 5 BP 683 EP 686 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ048 UT WOS:A1994PJ04800033 PM 7987231 ER PT J AU CARROLL, KM ROUNSAVILLE, BJ BRYANT, KJ AF CARROLL, KM ROUNSAVILLE, BJ BRYANT, KJ TI SHOULD TOLERANCE AND WITHDRAWAL BE REQUIRED FOR SUBSTANCE DEPENDENCE DISORDERS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE DSM-IV REVISION; SUBSTANCE DEPENDENCE DISORDERS; TOLERANCE AND WITHDRAWAL; ALCOHOL DEPENDENCE; COCAINE DEPENDENCE; OPIATE DEPENDENCE ID DSM-III; ABUSE AB Despite the historical importance of tolerance and withdrawal in the substance abuse nomenclature, empirical evaluations of tolerance and withdrawal relative to other, non-physical, dependence criteria have been infrequent. Based on data from 521 subjects rom a newly completed survey evaluating proposed options for DSM-IV substance use disorders, we found, first, across classes of drugs, requiring tolerance or withdrawal had little effect on rates of dependence, as most subjects who met dependence criteria for each drug class also reported tolerance. Second, tolerance and withdrawal did not emerge as superior to the other dependence criteria on several indicators of concurrent and predictive validity, including severity. C1 NIAAA,PREVENT BRANCH,ROCKVILLE,MD 20857. RP CARROLL, KM (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,DIV SUBST ABUSE,27 SYLVAN AVE,NEW HAVEN,CT 06519, USA. RI Carroll, Kathleen/A-7526-2009; OI Carroll, Kathleen/0000-0003-3263-3374 FU NIDA NIH HHS [R01 DA04029, R01 DA05592, R18 DA06963] NR 20 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG PY 1994 VL 36 IS 1 BP 15 EP 22 DI 10.1016/0376-8716(94)90004-3 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PD671 UT WOS:A1994PD67100003 PM 7988354 ER PT J AU CHILCOAT, HD MUNOZ, A VLAHOV, D ANTHONY, JC AF CHILCOAT, HD MUNOZ, A VLAHOV, D ANTHONY, JC TI LOW-POWER - USE 2-DIMENSIONAL CONFIDENCE-REGIONS AS A GRAPHICAL-METHOD FOR DEPICTING UNCERTAINTY SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE CONFIDENCE INTERVAL; CONFIDENCE REGION; HIV; DISINFECTANT; INJECTING DRUG USE; LIKELIHOOD ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTRAVENOUS DRUG-ABUSERS; RISK-FACTORS; COCAINE USE; INFECTION AB Prospective studies of rare outcomes, such as HIV seroconversion or obsessive-compulsive disorder, can often result in small sample sizes with limited power for detecting associations. For this reason, it is useful to develop graphical procedures that enable researchers to depict uncertainty around parameter estimates and examine the direction of association when statistical power is low. Classical procedures include the reporting of confidence intervals, which typically are derived from asymptotic normality of parameters estimated using large samples. In this paper, we present a likelihood-based procedure for the estimation of the confidence region of two parameters from a conditional logistic regression of a nested case-control study with a relatively small number of cases. Graphical depiction of the confidence regions provides an easily comprehensible procedure to quantify the uncertainty of the estimation based on small samples. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. MARYLAND DEPT HLTH & MENTAL HYG,BALTIMORE,MD. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP CHILCOAT, HD (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA05911, DA04334] NR 13 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG PY 1994 VL 36 IS 1 BP 39 EP 48 DI 10.1016/0376-8716(94)90008-6 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PD671 UT WOS:A1994PD67100007 PM 7988358 ER PT J AU DAWSON, DA AF DAWSON, DA TI ARE MEN OR WOMEN MORE LIKELY TO STOP DRINKING BECAUSE OF ALCOHOL-PROBLEMS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ALCOHOL PROBLEMS; WOMEN; SURVIVAL TECHNIQUES; GENDER ID DSM-III-R; LIVER-DISEASE; SEX-DIFFERENCES; UNITED-STATES; USE DISORDERS; DEPENDENCE; INTOXICATION; RISK AB Using a national population sample of adults who had ever consumed at least 12 drinks per year, men and women were compared in terms of the proportions who had stopped drinking because of alcohol problems. Overall, 24% of the male drinkers and 31% of the female drinkers had stopped drinking as of the time of interview, but men were more likely than women to have stopped drinking because of alcohol-related problems (4.3 vs 2.3%). After using survival techniques to adjust for women's greater competing risk of stopping drinking for other reasons and men's greater exposure time due to their earlier initiation of drinking, the conditional probabilities of having stopped drinking because of alcohol problems were almost identical for men and women during the first 15 years of their drinking histories. Thereafter, the conditional probabilities were 50% higher for men than for women. The observed durations of drinking history were about five years longer for men than women. After controlling for sociodemographic characteristics, family history of alcoholism, and patterns of alcohol consumption, there was no gender difference in the hazard of stopping drinking because of alcohol problems among persons who drank alcohol on less than a daily basis during their period of heaviest consumption. However, among daily drinkers, the hazard of stopping drinking because of alcohol problems was greater for women than men, by a factor of 1.5 to 3, depending on quantity of consumption and interval since first drink. RP DAWSON, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,SUITE 514,ROCKVILLE,MD 20892, USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG PY 1994 VL 36 IS 1 BP 57 EP 64 DI 10.1016/0376-8716(94)90010-8 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PD671 UT WOS:A1994PD67100009 PM 7988360 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI MANAGEMENT OF TOXOPLASMOSIS SO DRUGS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; CONGENITAL TOXOPLASMOSIS; CEREBRAL TOXOPLASMOSIS; PYRIMETHAMINE-SULFADOXINE; AIDS; ENCEPHALITIS; SULFADIAZINE; RETINOCHOROIDITIS; PROPHYLAXIS AB Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans. In immunocompetent hosts, the infection is usually asymptomatic and benign. Toxoplasmosis is either congenital or acquired. In general, prenatal therapy of congenital toxoplasmosis is beneficial inducing the frequency of infant infection. Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentrations achieved in the placenta. Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection. The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides. Toxoplasmic encephalitis is the most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal. However, because of toxicity, the therapeutic efficacy of pyrimethamine-sulphonamide combinations may be seriously limited in immunodeficient patients. A number of novel and less toxic agents are being currently studied in clinical settings, including macrolide antibiotics (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole). Maintenance or prophylactic therapy is essential in many patients with acquired immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of a pre-existent latent infection. RP STGEORGIEV, V (reprint author), NIAID,SOLAR BLDG,ROOM 4C-04,BETHESDA,MD 20892, USA. NR 59 TC 10 Z9 11 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD AUG PY 1994 VL 48 IS 2 BP 179 EP 188 DI 10.2165/00003495-199448020-00005 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PC616 UT WOS:A1994PC61600005 ER PT J AU CHRAMBACH, A WHEELER, DL AF CHRAMBACH, A WHEELER, DL TI CAPABILITIES AND POTENTIALITIES OF TRANSVERSE PORE GRADIENT GEL-ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article ID DNA FRAGMENTS; FERGUSON PLOT; CONFORMATION; MOBILITY; SYSTEM AB Transverse pore gradient gel electrophoresis is important as a tool for obtaining nonlinear Ferguson plots [log(mobility) vs. gel concentration], e.g. in application to DNA in polyacrylamide gels or to agarose gels, with the purpose of evaluating molecular properties (size, conformation, malleability) and gel fiber properties (fiber radius and length per unit volume). To date, it is capable of (i) yielding gel patterns (''Ferguson curves'') of migration distance vs. predicted %T-range of the pore gradient, assuming its linearity;(ii) yielding information regarding molecular conformation from the intersection of Ferguson curves of unknowns (e.g. bent DNA) with those of standards; (iii) acquisition of Ferguson curves by computer, using prototype instrumentation; (iv) mathematical manipulation of acquired Ferguson curves to yielding Ferguson plots, providing that mobility in free solution has been assessed by capillary zone electrophoresis. The potentialities of the method remain unfulfilled to date due to (i) the unavailability, with a single exception, of an accurate and precise way to produce pore gradients of known shape; (ii) unavailability of a routinely applicable analysis for %T; (iii) unavailability of optimized, user-friendly and foolproof instrumentation for computer acquisition of Ferguson curves, including the present inapplicability of a commercially available electrophoresis apparatus with intermittent optical detection to transverse pore gradient gels; and (iv) unresolved problems in the statistical evaluation of Ferguson curves. RP CHRAMBACH, A (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-215,BETHESDA,MD 20892, USA. NR 32 TC 8 Z9 8 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG-SEP PY 1994 VL 15 IS 8-9 BP 1021 EP 1027 DI 10.1002/elps.11501501152 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PL989 UT WOS:A1994PL98900004 PM 7859702 ER PT J AU BUZAS, Z WHEELER, DL GARNER, MM TIETZ, D CHRAMBACH, A AF BUZAS, Z WHEELER, DL GARNER, MM TIETZ, D CHRAMBACH, A TI TRANSVERSE PORE GRADIENT GEL-ELECTROPHORESIS, USING THE PHASTSYSTEM SO ELECTROPHORESIS LA English DT Article ID DNA AB The application of pore gradient gels prefabricated for the PhastSystem (Pharmacia) to transverse pore gradient gel electrophoresis is demonstrated. It has the twofold advantage of (i) horizontal positioning, avoiding gel stretching during the preparation of these gels and resulting pore size irreproducibility experienced with vertically applied pore gradient gels, which necessitate an orthogonal transfer of spacers, and (ii) miniaturized gel dimensions, which allow a small sample load and a short duration of electrophoresis and staining. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. AGR BIOTECHNOL CTR,INST BIOCHEM & PROT RES,H-2101 GODOLLO,HUNGARY. NIDDKD,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD. UNIV GIESSEN,W-6300 GIESSEN,GERMANY. NR 13 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG-SEP PY 1994 VL 15 IS 8-9 BP 1028 EP 1031 DI 10.1002/elps.11501501153 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PL989 UT WOS:A1994PL98900005 PM 7859703 ER PT J AU PULYAEVA, H ZAKHAROV, SF GARNER, MM CHRAMBACH, A AF PULYAEVA, H ZAKHAROV, SF GARNER, MM CHRAMBACH, A TI DETECTION OF A SINGLE-BASE MISMATCH IN DOUBLE-STRANDED DNA BY ELECTROPHORESIS ON UNCROSSLINKED POLYACRYLAMIDE-GEL SO ELECTROPHORESIS LA English DT Article ID POLYMER MEDIA; FRAGMENTS; PAIR AB Uncrosslinked polyacrylamide forms gels in the concentration range of 15-40% acrylamide. Electrophoresis in these gels of a commercially available 350 bp heteroduplex DNA preparation separates it from the homoduplex DNA of the same size. The separation is qualitatively equivalent to that previously achieved in a commercial proprietary gel (''Mutation Detection Gel'' of AT-Biochem), or in an equivalent 14%T, 0.15%C (N,N'-methylenebisacrylamide) gel, but the mechanical stability of mutation detection electrophoresis (MDE) gels or 0.15 %C gels is better than that of uncrosslinked polyacrylamide gels. The separation in any of these three gel media can be carried out in short gel tubes within a few hours of electrophoresis time. In both uncrosslinked polyacrylamide and MDE gel media, the Ferguson plots [log(mobility) vs. gel concentration] and the plots of effective molecular radius vs. gel concentration (''T-plots'') of both the heteroduplex and homoduplex DNA indicate an augmented size but similar flexibility upon passage through the gel than exhibited by the components of a DNA standard ladder. Homoduplex and heteroduplex DNA correspondingly exhibit a parallelism of their Ferguson curves in transverse MDE pore gradient gel electrophoresis, suggesting a surface net charge difference, possibly due to a conformational reorientation too subtle to be detected by a shift in the slope of the Ferguson plot, as has been observed once previously with a ''kinked'' DNA species. The gel fiber radius or length per unit volume of uncrosslinked polyacrylamide and MDE gels do not differ significantly within confidence limits, which are wide compared to conventionally crosslinked gels, presumably because of their greater swelling. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NHLBI,DIV INTRAMURAL RES,BETHESDA,MD 20892. NR 21 TC 7 Z9 7 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG-SEP PY 1994 VL 15 IS 8-9 BP 1095 EP 1100 DI 10.1002/elps.11501501164 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PL989 UT WOS:A1994PL98900016 PM 7859713 ER PT J AU ZAKHAROV, SF CHRAMBACH, A AF ZAKHAROV, SF CHRAMBACH, A TI THE RELATIVE SEPARATION EFFICIENCIES OF HIGHLY CONCENTRATED, UNCROSSLINKED OR LOW-CROSS-LINKED POLYACRYLAMIDE GELS COMPARED TO CONVENTIONAL GELS OF MODERATE CONCENTRATION AND CROSS-LINKING SO ELECTROPHORESIS LA English DT Article ID PERFORMANCE CAPILLARY ELECTROPHORESIS; CROSS-LINKED POLYACRYLAMIDE; DNA; FRAGMENTS AB The joint report [1] has shown that the separation of heteroduplex DNA from homoduplex DNA can be achieved by uncrosslinked polyacrylamide gels or gels of a very low degree of crosslinking (0.15%) with N,N'-methylenebisacrylamide (Bis), while conventional polyacrylamide gels of 2-5% crosslinking with Bis are incapable of such a separation in the absence of added denaturing agents. This result raised the question whether in application to other separation problems the same superiority of uncrosslinked or low-crosslinked polyacrylamide existed. To test that question, Ferguson plots were determined far the members of a DNA ladder (50 to 1000 bp) in polyacrylamide with 0, 0.1, 0.2, 0.3, 0.5%C (Bis), and the separation efficiency function, S, was evaluated in comparison with that in conventional 2-5%C (Bis) gels. S was found to be lower, not higher, in gels of low crosslinking at the respective maximally effective gel concentrations. However, the range of gel concentrations in which gels of low or no crosslinking were effective extended over a range of at least 10%T, while conventionally crosslinked gels were most effective over a range of 3 to 1 units of %T. RP CHRAMBACH, A (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C101,BETHESDA,MD 20892, USA. NR 14 TC 1 Z9 1 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG-SEP PY 1994 VL 15 IS 8-9 BP 1101 EP 1103 DI 10.1002/elps.11501501165 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PL989 UT WOS:A1994PL98900017 PM 7859714 ER PT J AU SATIN, LS SMOLEN, PD AF SATIN, LS SMOLEN, PD TI ELECTRICAL BURSTING IN BETA-CELLS OF THE PANCREATIC-ISLETS OF LANGERHANS SO ENDOCRINE LA English DT Review ID INSULIN-SECRETING CELLS; SENSITIVE K+ CHANNELS; ISOLATED RAT ISLETS; CYTOPLASMIC CA2+ OSCILLATIONS; 2 CALCIUM CURRENTS; B-CELLS; MOUSE ISLETS; CA-2+ CONCENTRATION; SODIUM-CHANNELS; GLUCOSE C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHYSIOL,RICHMOND,VA 23298. NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. RP SATIN, LS (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,BOX 524,RICHMOND,VA 23298, USA. NR 119 TC 34 Z9 34 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0969-711X J9 ENDOCRINE JI Endocrine PD AUG PY 1994 VL 2 IS 8 BP 677 EP 687 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QV195 UT WOS:A1994QV19500001 ER PT J AU VAMVAKOPOULOS, NC CHROUSOS, GP AF VAMVAKOPOULOS, NC CHROUSOS, GP TI HORMONAL-REGULATION OF HUMAN CORTICOTROPIN-RELEASING HORMONE GENE-EXPRESSION - IMPLICATIONS FOR THE STRESS-RESPONSE AND IMMUNE/INFLAMMATORY REACTION SO ENDOCRINE REVIEWS LA English DT Review ID PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE; GLUCOCORTICOID RECEPTOR-BINDING; WALL INDUCED POLYARTHRITIS; BLOOD MONONUCLEAR-CELLS; MESSENGER-RNA LEVELS; RAT LEYDIG-CELLS; TRANSCRIPTION FACTORS; ESTROGEN-RECEPTOR C1 UNIV THESSALY,SCH MED,DEPT BIOL,GR-41222 LARISA,GREECE. RP VAMVAKOPOULOS, NC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N260,BETHESDA,MD 20892, USA. NR 170 TC 134 Z9 134 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 1994 VL 15 IS 4 BP 409 EP 420 DI 10.1210/er.15.4.409 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD217 UT WOS:A1994PD21700001 PM 7988479 ER PT J AU STOJILKOVIC, SS REINHART, J CATT, KJ AF STOJILKOVIC, SS REINHART, J CATT, KJ TI GONADOTROPIN-RELEASING-HORMONE RECEPTORS - STRUCTURE AND SIGNAL-TRANSDUCTION PATHWAYS SO ENDOCRINE REVIEWS LA English DT Review ID PROTEIN-KINASE-C; RAT GRANULOSA-CELLS; ANTERIOR-PITUITARY-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; SENSITIVE CALCIUM CHANNELS; CYTOSOLIC FREE CALCIUM; FOLLICLE-STIMULATING-HORMONE; ULTRASHORT-LOOP FEEDBACK; PANCREATIC ACINAR-CELLS RP STOJILKOVIC, SS (reprint author), NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 49, ROOM 6A-36, BETHESDA, MD 20892 USA. NR 509 TC 371 Z9 388 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 1994 VL 15 IS 4 BP 462 EP 499 DI 10.1210/er.15.4.462 PG 38 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD217 UT WOS:A1994PD21700006 PM 7988482 ER PT J AU MONTROSERAFIZADEH, C EGAN, JM ROTH, J AF MONTROSERAFIZADEH, C EGAN, JM ROTH, J TI INCRETIN HORMONES REGULATE GLUCOSE-DEPENDENT INSULIN-SECRETION IN RIN-1046-38 CELLS - MECHANISMS OF ACTION SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC B-CELLS; BETA-CELLS; ADENYLATE-CYCLASE; CA-2+ CHANNELS; CYCLIC-AMP; GLUCAGON; RELEASE; CALCIUM; ISLETS; POLYPEPTIDE AB Glucagon-like peptide-1-(7-36) amide (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are known incretin hormones, released from enteroendocrine cells in response to food, that enhance insulin secretion, but only in the presence of elevated blood glucose. We used a rat insulinoma cell line, RIN 1046-38, to study the mechanisms underlying the interaction of incretins and glucose. We measured insulin secretion using RIA and the reverse hemolytic plaque assay. GLP-1 stimulates insulin secretion, with a half-maximal concentration of 34 pM. GLP-1 is approximately 2 orders of magnitude more potent than GIP. GLP-1 and GIP have additive effects at submaximal concentrations, but probably not at maximal concentrations, suggesting a common signal transduction pathway. The glucose requirement for GLP-1 action can be replaced by cell membrane depolarization (20 mM KCl in the extracellular medium), suggesting that a rise of intracellular Ca2+ may be an early step required for GLP-1 action. GLP-1 stimulates insulin secretion by significantly increasing the maximum rate of insulin secretion from 10.3 +/- 2.25 to 25.2 +/- 2.94 ng insulin/mg protein.h. GLP-1 acts by recruiting 1.5-fold more cells to secrete insulin as well as enhancing insulin secretion by individual cells. Combinations of stimuli, such as glucose, cell membrane depolarization, and GLP-1, can recruit 90% of RIN 1046-38 cells to secrete insulin. C1 JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. RP MONTROSERAFIZADEH, C (reprint author), NIA,GERONTOL RES CTR 2B02,CLIN PHYSIOL LAB,DIABET UNIT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 38 TC 38 Z9 38 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1994 VL 135 IS 2 BP 589 EP 594 DI 10.1210/en.135.2.589 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NZ288 UT WOS:A1994NZ28800014 PM 8033807 ER PT J AU CESNJAJ, M CATT, KJ STOJILKOVIC, SS AF CESNJAJ, M CATT, KJ STOJILKOVIC, SS TI COORDINATE ACTIONS OF CALCIUM AND PROTEIN-KINASE-C IN THE EXPRESSION OF PRIMARY RESPONSE GENES IN PITUITARY GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE RELEASE; CYTOSOLIC FREE CALCIUM; RECEPTOR ACTIVATION; HIPPOCAMPAL-NEURONS; SIGNALING PATHWAYS; FOS TRANSCRIPTION; GRANULOSA-CELLS; NERVOUS-SYSTEM; ANGIOTENSIN-II; BINDING-SITES AB Activation of GnRH receptors in cultured pituitary cells and alpha T3-1 gonadotrophs caused prominent, but transient, increases in messenger RNAs for primary response genes (PRGs) including c-fos, c-jun, and junB. GnRH-induced stimulation peaked at 30 min and was dose related, with similar EC(50) values (similar to 1 nM) for all three PRGs and higher maximum responses for junB than for c-jun, and c-fos. The agonist-induced expression of PRGs was mimicked by activation of protein kinase-C with the phorbol ester phorbol 12-myristate 13-acetate (PMA), which acted additively with GnRH at low concentrations of both stimuli. Depletion of cellular protein kinase-C by prior treatment with PMA reduced GnRH- and PMA-induced expression of PRGs. The protein kinase-C inhibitor staurosporine also attenuated agonist- and phorbol ester-induced PRG expression. Activation of Ca2+ entry by the calcium channel agonist BayK 8644 or high Kc-induced depolarization caused a concentration-dependent rise in intracellular Ca2+ ([Ca2+](i)) and a concentration-dependent and transient expression of PRGs, albeit of smaller amplitudes than those elicited by GnRH and PMA. Ca2+-dependent PRG expression was abolished by the calmodulin inhibitor W-7. Parallel measurements of [Ca2+](i) and steady-state levels of PRG messenger RNAs indicated that intracellular Ca2+ exerted both additive and suppressive actions over its physiological concentration range on GnRH- and PMA-induced PRG expression. At lower intracellular calcium concentrations, calcium acted additively with low concentrations of GnRH and PMA. However, high calcium concentrations suppressed high agonist- and phorbol ester-induced PRG expression. In contrast, omission of Ca2+ from the extracellular medium significantly enhanced induction of PRGs. These findings indicate that GnRH-induced PRG expression in gonadotrophs is mediated by protein kinase-C and calcium, and that protein kinase-C-dependent induction of PRGs is modulated both positively and negatively by physiological changes in [Ca2+](i). Such coordinate actions of the two signaling molecules provide a mechanism for the control of PRG expression by preferential integration of low strength, and attenuation of high strength, extracellular signals. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 53 TC 58 Z9 58 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1994 VL 135 IS 2 BP 692 EP 701 DI 10.1210/en.135.2.692 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NZ288 UT WOS:A1994NZ28800028 PM 7518388 ER PT J AU ROMAGNOLO, D DIAUGUSTINE, RP AF ROMAGNOLO, D DIAUGUSTINE, RP TI THE MAMMARY-GLAND - PROTEIN FACTORY OF THE FUTURE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID HIGH-LEVEL EXPRESSION; MILK; PROSPECTS RP ROMAGNOLO, D (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,HORMONES & CANC WORKGRP,BETHESDA,MD, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1994 VL 102 IS 8 BP 644 EP 646 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PC373 UT WOS:A1994PC37300006 PM 7895703 ER PT J AU LAZARUS, LH BRYANT, SD ATTILA, M SALVADORI, S AF LAZARUS, LH BRYANT, SD ATTILA, M SALVADORI, S TI FROG-SKIN OPIOID-PEPTIDES - A CASE FOR ENVIRONMENTAL MIMICRY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE AMPHIBIANS; DELTORPHIN; DERMORPHIN; EVOLUTION; MIMICRY; MOLECULAR MODELING; OPIATE ADDICTION; OPIOID PEPTIDES; PEPTIDE SYNTHESIS ID AMPHIBIAN SKIN; HIGH-AFFINITY; MOLECULAR-CLONING; OPIATE RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; DELTORPHIN ANALOGS; IMMUNE-SYSTEM; RAT-BRAIN; DELTA; MU AB Naturally occurring environmental substances often mimic endogenous substances found in mammals and are capable of interacting with specific proteins, such as receptors, with a high degree of fidelity and selectivity. Narcotic alkaloids and amphibian skin secretions, introduced into human society through close association with plants and animals through folk medicine and religious divination practices, were incorporated into the armamentarium of the early pharmacopoeia. These skin secretions contain a myriad of potent bioactive substances, including alkaloids, biogenic amines, peptides, enzymes, mucus, and toxins (noxious compounds notwithstanding); each class exhibits a broad range of characteristic properties. One specific group of peptides, the opioids, containing the dermorphins (dermal morphinelike substances) and the deltorphins (delta-selective opioids), display remarkable analgesic properties and include an amino acid with the rare (in a mammalian context) D-enantiomer in lieu of the normal L-isomer. Synthesis of numerous stereospecific analogues and conformational analyses of these peptides provided essential insights into the tertiary composition and microenvironment of the receptor ''pocket'' and the optimal interactions between receptor and ligand that trigger a biological response; new advances in the synthesis and receptor-binding properties of the deltorphins are discussed in detail. These receptor-specific opioid peptides act as more than mimics of endogenous opioids: their high selectivity for either the mu or delta receptor makes them formidable environmentally derived agents in the search for new antagonists for treating opiate addiction and in the treatment of a wide variety of human disorders. C1 UNIV HELSINKI, DEPT PHARM, SF-00014 HELSINKI, FINLAND. UNIV FERRARA, DEPT PHARMACEUT SCI, I-44100 FERRARA, ITALY. RP NIEHS, ENVIRONM NEUROSCI LAB, POB 12233, MD C3-04, RES TRIANGLE PK, NC 27709 USA. OI SALVADORI, Severo/0000-0002-8224-2358 NR 88 TC 19 Z9 21 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1994 VL 102 IS 8 BP 648 EP 654 DI 10.2307/3432193 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PC373 UT WOS:A1994PC37300007 PM 7895704 ER PT J AU WAGENER, DK HARRIS, T MADANS, JH AF WAGENER, DK HARRIS, T MADANS, JH TI PROTEINURIA AS A BIOMARKER - RISK OF SUBSEQUENT MORBIDITY AND MORTALITY SO ENVIRONMENTAL RESEARCH LA English DT Article ID INFORMATION; SMOKING AB A standard laboratory renal assessment, concentration of albumin in urine, has been suggested as a biomarker of renal damage, but little data exist on its ability to predict health outcomes in the general population. This 16-year follow-up study of a general population evaluated the utility of this assessment to predict subsequent serious health consequences. Four percent of men and 2% of women aged 45-74 years exhibited proteinuria in a cross-sectional screening of an ambulatory population, with the percentage increasing with age. The finding of proteinuria was predictive of serious health consequences, with adjusted relative risks for subsequent mortality of 1.71 for men and 1.84 for women and adjusted relative risks for renal disease incidence of 3.46 in men and 1.39 in women. Controlling for those factors which might be associated with proteinuria and even excluding early cases did not alter these findings. These data support that casual proteinuria should be considered as a marker for risk of poor health outcomes. C1 NIA, BETHESDA, MD 20816 USA. RP WAGENER, DK (reprint author), CTR DIS CONTROL & PREVENT, NATL CTR HLTH STAT, OFF ANAL & EPIDEMIOL, HYATTSVILLE, MD 20782 USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD AUG PY 1994 VL 66 IS 2 BP 160 EP 172 DI 10.1006/enrs.1994.1052 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA PC107 UT WOS:A1994PC10700004 ER PT J AU SANDERS, BM MARTIN, LS NAKAGAWA, PA HUNTER, DA MILLER, S ULLRICH, SJ AF SANDERS, BM MARTIN, LS NAKAGAWA, PA HUNTER, DA MILLER, S ULLRICH, SJ TI SPECIFIC CROSS-REACTIVITY OF ANTIBODIES RAISED AGAINST 2 MAJOR STRESS PROTEINS, STRESS-70 AND CHAPERONIN-60, IN DIVERSE SPECIES SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Stress Proteins and the Environment, at the 1992 Annual SETAC Meeting CY 1992 CL CINCINNATI, OH SP SOC ENVIRONM TOXICOL & CHEM DE STRESS-70; CHAPERONIN-60; STRESS PROTEINS; BIOMARKERS; ANTIBODIES ID HEAT-SHOCK PROTEINS; HSP70 MULTIGENE FAMILY; CAENORHABDITIS-ELEGANS; POLYACRYLAMIDE GELS; CELL; LOCALIZATION; BINDING; HSP60; INTERMEDIATE; AGGREGATION AB Immunoblot analysis using several antibodies raised against two major families of stress proteins, stress 70 and chaperonin 60 (cpn60), which are highly conserved in mammals, was carried out in diverse species often used in environmental research, including molluscs, annelids, crustaceans, echinoderms, and fish. The study revealed surprisingly different patterns of antibody cross-reactivity among species. The monoclonal anti-stress 70 antibody (mAb) C92 was the least cross-reactive for all species tested. The mAbs anti-stress 70 N27, BRM-22, and 3a3 were more broadly cross-reactive, but their binding specificities to stress 70 isoforms in the diverse species tested did not correlate with one another or follow taxonomic lines. The polyclonal anti-stress 70 antibody reacted to proteins in the 70 to 74 kDa range in all fish examined and in most invertebrates. When a polyclonal antibody (pAb) raised against cpn60 from a moth was used as a probe, specific binding was observed with proteins in the 60 to 64 kDa range in all fish examined and in most invertebrates. However, the size and number of isoforms that reacted with the pAb were species specific. These data suggest that these two major stress protein families are less highly conserved in invertebrates and fish than in mammals. Therefore, to minimize misinterpretation when using antibodies in heterologous assays with species in which the stress response has not been well characterized, it is important to determine which isoforms of stress 70 react with a particular antibody and to take into account the differential regulation of each member of this multigene family. C1 CALIF STATE UNIV LONG BEACH,DEPT BIOL,LONG BEACH,CA 90840. ODENSE UNIV,INST BIOL,DK-5230 ODENSE,DENMARK. USDA,GAINESVILLE,FL 32604. NCI,BETHESDA,MD 20892. RP SANDERS, BM (reprint author), CALIF STATE UNIV LONG BEACH,INST MOLEC ECOL,LONG BEACH,CA 90840, USA. NR 52 TC 34 Z9 36 U1 2 U2 3 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD AUG PY 1994 VL 13 IS 8 BP 1241 EP 1249 DI 10.1897/1552-8618(1994)13[1241:SCOARA]2.0.CO;2 PG 9 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA NZ712 UT WOS:A1994NZ71200005 ER PT J AU TAKAHASHI, N BREITMAN, T AF TAKAHASHI, N BREITMAN, T TI UNASSEMBLED (SOLUBLE) VIMENTIN IN HUMAN MYELOID-LEUKEMIA CELL-LINE HL-60 SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE CELL DIFFERENTIATION; VIMENTIN; DESMIN ID INTERMEDIATE FILAMENT PROTEINS; RETINOIC ACID; MACROPHAGE DIFFERENTIATION; GENE-EXPRESSION; INDUCTION; HL-60; RETINOYLATION; GROWTH; CYTOSKELETON; PURIFICATION AB The intermediate filament proteins which include vimentin, desmin, and the keratins are one of three major classes of cytoskeletal proteins in eukaryotic cells. In this study we found that most of the vimentin of undifferentiated HL60 and cells induced to differentiate either along the monocytoid pathway by 12-O-tetradecanoylphorbol-13-acetate (TPA) or along the granulocytic pathway by retinoic acid was soluble in a buffer containing 1% Triton X-100/0.6 mol/l KCl in which the intermediate filament proteins usually are not soluble. HL60 virnentin separated on polyacrylamide gel electrophoresis into two proteins of Mr 55 000 and 54 000 that we detected by immunoblotting. The Mr 55 000 species was the major form in undifferentiated HL60 cells and cells induced by retinoic acid. The distribution of both forms of vimentin changed during induction of differentiation by TPA and after 24 h the Mr 54 000 species was predominant. After an additional 24 h exposure to TPA the relative levels of the two forms of vimentin approached equivalence and a high level of vimentin degradation products was seen. These results suggest that TPA may increase vimentin degradation along a pathway that has a Mr 54 000 intermediate. In addition, the high levels of soluble vimentin in HL60 cells suggests that these cells may be a good model for studying components involved in vimentin assembly. RP TAKAHASHI, N (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892, USA. NR 48 TC 4 Z9 4 U1 0 U2 0 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 AUG PY 1994 VL 53 IS 2 BP 78 EP 84 PG 7 WC Hematology SC Hematology GA PG270 UT WOS:A1994PG27000003 PM 7522191 ER PT J AU MOCK, BA KRALL, MM BYRD, LG CHIN, H BARTON, CH CHARLES, I LIEW, FY BLACKWELL, J AF MOCK, BA KRALL, MM BYRD, LG CHIN, H BARTON, CH CHARLES, I LIEW, FY BLACKWELL, J TI THE INDUCIBLE FORM OF NITRIC-OXIDE SYNTHASE (NOS2) ISOLATED FROM MURINE MACROPHAGES MAPS NEAR THE NUDE MUTATION ON MOUSE CHROMOSOME-11 SO EUROPEAN JOURNAL OF IMMUNOGENETICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; LEISHMANIA-MAJOR AMASTIGOTES; DEPENDENT KILLING MECHANISM; INORGANIC NITROGEN-OXIDES; NONOBESE DIABETIC MICE; L-ARGININE; ACTIVATED MACROPHAGES; CALCIUM-CHANNEL; BETA-SUBUNIT; TUMOR-CELLS AB Nitric oxide synthase has been shown to mediate streptozocin-induced diabetes and to act as an antimicrobial agent in murine macrophages. Using a cDNA probe for the inducible form of nitric oxide synthase (Nos2) isolated from murine macrophages we have determined that the gene maps within 1 cM of the nude mutation on mouse Chromosome 11. The position of Nos2 was also mapped relative to the markers I15, Evi2, Cchlb1 (previously unmapped), and Gfap, This map location is discussed I relative to map locations for disease susceptibility loci involved in mediating cutaneous leishmaniasis (Sell) and autoimmune type-I diabetes (Idd4). C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. ADDENBROOKES HOSP,DEPT MED,CAMBRIDGE CB2 2QQ,ENGLAND. WELLCOME RES LABS,DEPT CELL BIOL,BECKENHAM BR3 3BS,KENT,ENGLAND. UNIV GLASGOW,DEPT IMMUNOL,GLASGOW,SCOTLAND. RP MOCK, BA (reprint author), NCI,GENET LAB,BLDG 37,RM 2B-08,BETHESDA,MD 20892, USA. RI Blackwell, Jenefer/H-3015-2015 NR 52 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7420 J9 EUR J IMMUNOGENET JI Eur. J. Immunogenet. PD AUG PY 1994 VL 21 IS 4 BP 231 EP 238 DI 10.1111/j.1744-313X.1994.tb00196.x PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA NZ592 UT WOS:A1994NZ59200002 PM 9098436 ER PT J AU MURPHY, WJ TAUB, DD ANVER, M CONLON, K OPPENHEIM, JJ KELVIN, DJ LONGO, DL AF MURPHY, WJ TAUB, DD ANVER, M CONLON, K OPPENHEIM, JJ KELVIN, DJ LONGO, DL TI HUMAN RANTES INDUCES THE MIGRATION OF HUMAN T-LYMPHOCYTES INTO THE PERIPHERAL-TISSUES OF MICE WITH SEVERE COMBINED IMMUNE-DEFICIENCY SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CHEMOKINES; HUMAN MOUSE CHIMERA; TRAFFICKING; T LYMPHOCYTE; RANTES ID CYTOKINE FAMILY; MOUSE; ENGRAFTMENT; MIP-1-BETA; CHIMERAS; SYSTEM; MURINE; CELLS; MODEL AB The human cytokine, Recombinant Human Regulated on Activation, Normal T Expressed and Secreted (rhRANTES), is a small glycoprotein secreted by activated T cells and platelets and is structurally related to a family of chemotactic cytokines called chemokines. Evaluation of the effects of chemokines on human cells has largely been limited to in vitro binding assays. In an effort to study the in vivo effects of chemokines on human leukocyte migration, we examined the ability of rhRANTES to induce human T cell infiltration using a human/severe combined immune deficient (SCID) mouse model. SCID mice received human peripheral blood lymphocytes, followed by sequential subcutaneous injections of rhRANTES in the hind flank for 3 days. The skin and underlying tissue from the rhRANTES injection site were then biopsied and examined for the extent of human mononuclear cell infiltration. rhRANTES induced significant mononuclear cell accumulation 72 h after injection. Immunohistological evaluation determined that the majority of the cells recruited in response to rhRANTES injections were human CD3(+) T cells with equal numbers of CD4(+) and CD8(+) cells. In contrast, subcutaneous injections of recombinant human macrophage colony-stimulating factors resulted in little human cellular infiltration. Murine mononuclear cell infiltration in response to rhRANTES was also present suggesting that the in vivo effects of rhRANTES may be both direct and indirect. These results demonstrate that rhRANTES induces significant human T cell migration in vivo and suggests that the human/SCID mouse model may provide an important tool in studying the in vivo effects of chemokines on human leukocytes and leukocyte subsets. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,BLDG 567,FREDERICK,MD 21702, USA. NR 14 TC 58 Z9 59 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 AUG PY 1994 VL 24 IS 8 BP 1823 EP 1827 DI 10.1002/eji.1830240815 PG 5 WC Immunology SC Immunology GA PC638 UT WOS:A1994PC63800014 PM 7519996 ER PT J AU MURRAY, DM MCKINLAY, SM MARTIN, D DONNER, AP DWYER, JH RAUDENBUSH, SW GRAUBARD, BI AF MURRAY, DM MCKINLAY, SM MARTIN, D DONNER, AP DWYER, JH RAUDENBUSH, SW GRAUBARD, BI TI DESIGN AND ANALYSIS ISSUES IN COMMUNITY TRIALS SO EVALUATION REVIEW LA English DT Article ID HEART HEALTH-PROGRAM; CARDIOVASCULAR-DISEASE; WIDE PREVENTION; INTERVENTION; RANDOMIZATION; VARIANCE; MODEL; STRATEGIES; EDUCATION; PROMOTION AB The National Institutes of Health sponsored a conference on the Design and Analysis Issues in Community Trials on March 23, 1992, in Bethesda, MD. This article presents a synopsis of each of the seven presentations given at that conference and summarizes the discussion that followed. C1 UNIV WASHINGTON,SEATTLE,WA 98195. UNIV WESTERN ONTARIO,LONDON N6A 3K7,ONTARIO,CANADA. UNIV SO CALIF,LOS ANGELES,CA 90089. MICHIGAN STATE UNIV,E LANSING,MI 48824. NCI,BETHESDA,MD 20892. NEW ENGLAND RES INST INC,WATERTOWN,MA. RP MURRAY, DM (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55455, USA. NR 50 TC 27 Z9 27 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD AUG PY 1994 VL 18 IS 4 BP 493 EP 514 DI 10.1177/0193841X9401800407 PG 22 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA PA114 UT WOS:A1994PA11400007 ER PT J AU BUSETTINI, C MILES, FA SCHWARZ, U CARL, JR AF BUSETTINI, C MILES, FA SCHWARZ, U CARL, JR TI HUMAN OCULAR RESPONSES TO TRANSLATION OF THE OBSERVER AND OF THE SCENE - DEPENDENCE ON VIEWING DISTANCE SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE EYE MOVEMENTS; TRANSLATIONAL MOTION; OCULAR FOLLOWING; VIEWING DISTANCE; HUMAN ID EYE-MOVEMENT RESPONSES; VESTIBULOOCULAR REFLEX; OPTOKINETIC NYSTAGMUS; HEAD ROTATION; LINEAR MOTION; MONKEY; MECHANISMS AB Recent experiments on monkeys have indicated that the eye movements induced by brief translation of either the observer or the visual scene are a linear function of the inverse of the viewing distance. For the movements of the observer, the room was dark and responses were attributed to a translational vestibule-ocular reflex (TVOR) that senses the motion through the otolith organs; for the movements of the scene, which elicit ocular following, the scene was projected and adjusted in size and speed so that the retinal stimulation was the same at all distances. The shared dependence on viewing distance was consistent with the hypothesis that the TVOR and ocular following are synergistic and share central pathways. The present experiments looked for such dependencies on viewing distance in human subjects. When briefly accelerated along the interaural axis in the dark, human subjects generated compensatory eye movements that were also a linear function of the inverse of the viewing distance to a previously fixated target. These responses, which were attributed to the TVOR, were somewhat weaker than those previously recorded from monkeys using similar methods. When human subjects faced a tangent screen onto which patterned images were projected, brief motion of those images evoked ocular following responses that showed statistically significant dependence on viewing distance only with low-speed stimuli (10 degrees/s). This dependence was at best weak and in the reverse direction of that seen with the TVOR, i.e., responses increased as viewing distance increased. We suggest that in generating an internal estimate of viewing distance subjects may have used a confounding cue in the ocular-following paradigm the size of the projected scene - which was varied directly with the viewing distance in these experiments (in order to preserve the size of the retinal image). When movements of the subject were randomly interleaved with the movements of the scene - to encourage the expectation of ego-motion - the dependence of ocular following on viewing distance altered significantly: with higher speed stimuli (40 degrees/s) many responses (63%) now increased significantly as viewing distance decreased, though less vigorously than the TVOR. We suggest that the expectation of motion results in the subject placing greater weight on cues such as vergence and accommodation that provide veridical distance information in our experimental situation: cue selection is context specific. C1 NIH,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. UNIV TRIESTE,DIPARTIMENTO ELETTROTECN ELETTRON & INFORMAT,I-34100 TRIESTE,ITALY. NR 34 TC 76 Z9 76 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD AUG PY 1994 VL 100 IS 3 BP 484 EP 494 DI 10.1007/BF02738407 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PF280 UT WOS:A1994PF28000011 PM 7813684 ER PT J AU GARG, A TOMASZEWSKI, JE BARBERAGUILLEM, E MURPHY, MJ AF GARG, A TOMASZEWSKI, JE BARBERAGUILLEM, E MURPHY, MJ TI IN-VITRO BONE-MARROW TOXICITY OF THE ANTINEOPLASTIC DRUG, BIZELESIN (NSC-615921) SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 HIPPLE CANC RES CTR,DAYTON,OH. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 712 EP 712 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800131 ER PT J AU JAIN, VK SEEM, N GESELOVITZ, D NECKERS, D MAGRATH, I AF JAIN, VK SEEM, N GESELOVITZ, D NECKERS, D MAGRATH, I TI INHIBITION OF IMMUNOGLOBULIN HEAVY-CHAIN (MU)-ENHANCER ACTIVITY BY A DNA OLIGOMER DIRECTED AT THE (MU)E4-MOTIF INHIBITS C-MYC TRANSCRIPTION IN BURKITTS-LYMPHOMA SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 718 EP 718 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800150 ER PT J AU CHAN, CH BLAZAR, BR EIDE, CR KREITMAN, RJ WAGNER, JE FULLER, SK GREENFIELD, L VALLERA, DA AF CHAN, CH BLAZAR, BR EIDE, CR KREITMAN, RJ WAGNER, JE FULLER, SK GREENFIELD, L VALLERA, DA TI CONSTRUCTION OF A NOVEL MURINE CYTOKINE FUSION TOXIN SPECIFICALLY TARGETING THE MURINE INTERLEUKIN-3 RECEPTOR SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV MINNESOTA,HOFFMANN LA ROCHE,MINNEAPOLIS,MN 55455. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 719 EP 719 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800154 ER PT J AU WARREN, MK ROSE, WL SCHWARTZ, GN AF WARREN, MK ROSE, WL SCHWARTZ, GN TI CD34+ CELL EXPANSION AND EXPRESSION OF LINEAGE MARKERS DURING LIQUID CULTURE OF HUMAN PROGENITOR CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 726 EP 726 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800180 ER PT J AU MARTENS, ACM ROZEMULLER, H ROMBOUTS, WJC GAISER, JF DONG, F FITZGERALD, D KREITMAN, RJ PASTAN, I TOUW, IP HAGENBEEK, A AF MARTENS, ACM ROZEMULLER, H ROMBOUTS, WJC GAISER, JF DONG, F FITZGERALD, D KREITMAN, RJ PASTAN, I TOUW, IP HAGENBEEK, A TI EFFECT OF GROWTH FACTOR-TOXIN FUSION PROTEINS IN A RAT MODEL FOR HUMAN ACUTE MYELOCYTIC-LEUKEMIA SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,INST HEMATOL,ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,3008 AE ROTTERDAM,NETHERLANDS. NCI,DCBCD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 730 EP 730 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800193 ER PT J AU SCHWARTZ, GN WARREN, MK SAKANO, K KESSLER, SW SZABO, JM PERDUE, JF AF SCHWARTZ, GN WARREN, MK SAKANO, K KESSLER, SW SZABO, JM PERDUE, JF TI EFFECT OF INSULIN-LIKE GROWTH-FACTOR-II (IGF-II) MUTANTS SPECIFIC FOR IGF-II CIM6-P OR IGF-I RECEPTORS ON IN-VITRO HEMATOPOIESIS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD. DALICHI PHARM CO,TOKYO,JAPAN. AMER RED CROSS,ROCKVILLE,MD. OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 744 EP 744 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800248 ER PT J AU DALAL, BI JOHNSTON, JB YUEN, A PARIKH, NB MCCORMAC, S FLANDERS, K AF DALAL, BI JOHNSTON, JB YUEN, A PARIKH, NB MCCORMAC, S FLANDERS, K TI CANCER CELL-DERIVED TRANSFORMING GROWTH FACTOR-B1 (TGF-B1) IS ASSOCIATED WITH MYELOFIBROSIS IN HEMATOLOGIC MALIGNANCIES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 VANCOUVER GEN HOSP,VANCOUVER,BC,CANADA. MANITOBA CANC TREATMENT & RES FDN,WINNIPEG R3E 0V9,MB,CANADA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1994 VL 22 IS 8 BP 771 EP 771 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PB368 UT WOS:A1994PB36800348 ER PT J AU OKOYE, GS FREED, WJ GELLER, HM AF OKOYE, GS FREED, WJ GELLER, HM TI SHORT-TERM IMMUNOSUPPRESSION ENHANCES THE SURVIVAL OF INTRACEREBRAL GRAFTS OF A7-IMMORTALIZED GLIAL-CELLS SO EXPERIMENTAL NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; FETAL DOPAMINE NEURONS; CENTRAL-NERVOUS-SYSTEM; DEEP CERVICAL LYMPH; PARKINSONS-DISEASE; SUSPENSION GRAFTS; NEURAL GRAFTS; RAT MODEL; TRANSPLANTATION; TISSUE AB The A7 cell line is an astrocyte cell line produced by immortalizing optic nerve astrocytes from the embryonic Sprague-Dawley rat with SV40 large T antigen. In a previous study, we found that grafts of A7 cells into Sprague-Dawley rats survived unreliably and only for a short time after grafting into the striatum. The current experiment was designed to investigate whether short-term immunosuppression with cyclosporin A could enhance the survival of the A7 cells grafted into the adult rat striatum. A7 cells were labeled with l,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI) and stereotactically grafted into the left striatum of adult rat brains. Some of the host animals received cyclosporin A until 30 or 60 days after grafting. Animals were sacrificed after periods of up to 90 days, and the number and location of surviving A7 cells were determined by counting the DiI-labeled A7 cells. The possible infiltration of the host animal immune cells into the A7 grafts was evaluated using antibodies that recognize lymphocyte and macrophage antigens (anti-CD8 and anti-CD4). There was a dramatic loss of cells with time in the untreated control animals. Shortterm immunosuppression with cyclosporin A significantly increased the average number of surviving A7 cells at all time points examined (30, 60, and 90 days). There was no difference in the number of surviving A7 cells between animals that received a short course of immunosuppression and those that received continuous immunosuppression for 60 days. In general, the levels of CD4 immunoreactivity in the vicinity of the A7 grafts were inversely correlated with A7 cell survival. This suggests that the host animals reacted to the A7 grafts as allografts. These results indicate that the short-term immunosuppression regimen is capable of enhancing the survival of intrastriatal grafts of the A7 astrocyte cell line. (C) 1994 Academic Press, Inc. C1 UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT PHARMACOL, PISCATAWAY, NJ 08854 USA. RUTGERS STATE UNIV, GRAD PROGRAM PHARMACOL, PISCATAWAY, NJ 08854 USA. NIMH, NEUROSCI CTR ST ELIZABETHS, WASHINGTON, DC 20032 USA. RP UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT SURG, DIV NEUROSURG, PISCATAWAY, NJ 08854 USA. OI Geller, Herbert/0000-0002-7048-6144 FU NIMH NIH HHS [T32 MH 19547]; NINDS NIH HHS [P01 NS 21469] NR 51 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1994 VL 128 IS 2 BP 191 EP 201 DI 10.1006/exnr.1994.1127 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PE963 UT WOS:A1994PE96300004 PM 8076662 ER PT J AU GEHRMANN, J YAO, DL BONETTI, B BONDY, CA BRENNER, M ZHOU, J KREUTZBERG, GW WEBSTER, HD AF GEHRMANN, J YAO, DL BONETTI, B BONDY, CA BRENNER, M ZHOU, J KREUTZBERG, GW WEBSTER, HD TI EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I AND RELATED PEPTIDES DURING MOTONEURON REGENERATION SO EXPERIMENTAL NEUROLOGY LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; RECEPTOR GENE-EXPRESSION; FACIAL-NERVE AXOTOMY; RAT-BRAIN; IGF-I; CELLULAR-PATTERN; MICROGLIAL CELLS; BINDING-PROTEINS; MOTOR NEURONS; ASTROCYTES AB The regulation of insulin-like growth factor-I (IGF-I) and related peptides during motoneuron regeneration was examined in the facial nerve following facial nerve transection. One to 39 days after axotomy, the mRNAs and peptides of IGF-I, type-I insulin-like growth factor receptor (IGFR), insulin-like growth factor binding proteins 1-5 (IGFBP-1-5), and glial fibrillary acidic protein (GFAP) were assayed in brain stem sections by in situ hybridization and immunohistochemistry. Relative mRNA levels of IGF I, IGFR, IGFBP-2, and GFAP in the ipsilateral facial nucleus were highest 4-7 days after transection and declined thereafter. Double immunostaining experiments showed that both IGF-I and IGFBP-2 were localized in GFAP-positive astrocytic processes, many of which were perineuronal. Peak staining intensity was found 4-7 days after transection and immunoreactivity still was present after 21-35 days. IGFR mRNA was found in some regenerating neurons; however, IGFR peptide was not detected in these neurons or in any other cells in the facial nucleus. Our findings suggest that astrocytic production of IGF-I and IGFBP-2 may accompany regeneration of neurons undergoing retrograde changes induced by axotomy. C1 NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. MAX PLANCK INST PSYCHIAT,DEPT NEUROMORPHOL,D-82152 MARTINSRIED,GERMANY. NINCDS,STROKE BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 45 TC 55 Z9 58 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1994 VL 128 IS 2 BP 202 EP 210 DI 10.1006/exnr.1994.1128 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PE963 UT WOS:A1994PE96300005 PM 8076663 ER PT J AU SHAHABUDDIN, M KASLOW, DC AF SHAHABUDDIN, M KASLOW, DC TI PLASMODIUM - PARASITE CHITINASE AND ITS ROLE IN MALARIA TRANSMISSION SO EXPERIMENTAL PARASITOLOGY LA English DT Review ID PERITROPHIC MEMBRANE; MOSQUITO; PENETRATION; PROTEASE; DIPTERA RP SHAHABUDDIN, M (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD 20892, USA. NR 10 TC 64 Z9 64 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD AUG PY 1994 VL 79 IS 1 BP 85 EP 88 DI 10.1006/expr.1994.1066 PG 4 WC Parasitology SC Parasitology GA PC640 UT WOS:A1994PC64000014 PM 7914174 ER PT J AU SHARARA, FI BEATSE, SN LEONARDI, MR NAVOT, D SCOTT, RT AF SHARARA, FI BEATSE, SN LEONARDI, MR NAVOT, D SCOTT, RT TI CIGARETTE-SMOKING ACCELERATES THE DEVELOPMENT OF DIMINISHED OVARIAN RESERVE AS EVIDENCED BY THE CLOMIPHENE CITRATE CHALLENGE TEST SO FERTILITY AND STERILITY LA English DT Article DE OVARY; OVARIAN RESERVE; SMOKING; IN VITRO FERTILIZATION; CLOMIPHENE CITRATE; CLOMIPHENE CITRATE CHALLENGE TEST ID STIMULATING-HORMONE LEVELS; INVITRO FERTILIZATION; OVULATION INDUCTION; FEMALE FECUNDITY; EMBRYO TRANSFER; HYPERSTIMULATION; REPRODUCTION; IMPLANTATION; PREDICTION; MENOPAUSE AB Objective: To test whether the reduced fecundity in women who smoke cigarettes may be attributed to the accelerated development of diminished ovarian reserve. Design: Retrospective evaluation of clomiphene citrate (CC) challenge tests in women from a general infertility population who did and did not smoke cigarettes (part 1) and retrospective evaluation of the impact of smoking on pregnancy rates (PRs) in IVF among women with normal ovarian reserve (part 2). Setting: Large military tertiary care center. Patients: Sixty-five women who smoked cigarettes and 145 women who did not smoke cigarettes in the general infertility population (part 1) and women undergoing IVF for strict tubal factor infertility with normal ovarian reserve who did (n = 29) and did not (n = 73) smoke (part 2). Interventions: Clomiphene citrate challenge tests, composed of FSH levels on cycle days 3 and 10 with 100 mg of CC administered on cycle days 5 through 9. Main Outcome Measures: Comparison of the incidence of abnormal CC challenge test results between women who did and did not smoke, and comparison of peak E(2) levels, number of mature follicles, number of mature oocytes retrieved, fertilization rates, and total and ongoing PRs. Results: The incidence of diminished ovarian reserve was increased in women who smoked (8 of 65 [12.31%]) when compared with age-matched controls who did not smoke (7 of 145 [4.83%]). Among women with normal CC challenge tests who were undergoing IVF, there were no differences in peak E(2) levels, the number of mature follicles, the number of mature oocytes retrieved, fertilization rates, or total and ongoing PRs. Conclusion: Women who smoke have an accelerated development of clinically detectable diminished ovarian reserve. Additionally, the fact that women who smoke cigarettes with normal ovarian reserve have ovarian responses and PRs that are equivalent to age-matched nonsmoking controls suggests that diminished ovarian reserve may be a principal mechanism reducing fecundity among women who smoke cigarettes. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT OBSTET & GYNECOL,BETHESDA,MD 20814. NEW YORK MED COLL,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL,VALHALLA,NY. WILFORD HALL USAF MED CTR,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL,LACKLAND AFB,TX 78236. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NR 25 TC 77 Z9 79 U1 0 U2 2 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 1994 VL 62 IS 2 BP 257 EP 262 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NY085 UT WOS:A1994NY08500008 PM 8034069 ER PT J AU BUCHER, JR SHACKELFORD, CC HASEMAN, JK JOHNSON, JD KURTZ, PJ PERSING, RL AF BUCHER, JR SHACKELFORD, CC HASEMAN, JK JOHNSON, JD KURTZ, PJ PERSING, RL TI CARCINOGENICITY STUDIES OF OXAZEPAM IN MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; BENZODIAZEPINE RECEPTORS; MOUSE-LIVER; ANIMAL CARCINOGENICITY; REGRESSION-ANALYSIS; STATISTICAL ISSUES; PROMOTING ACTIVITY; DIAZEPAM; RATS; TUMORS AB Oxazepam is a benzodiazepine widely used as a sedative-hypnotic and antianxiety drug. In chronic studies, groups of 60 male and 60 female Swiss-Webster (SW) or B6C3F(1) mice received oxazepam in feed at concentrations of 0, 2500, or 5000 ppm. Additional groups of 60 male and female B6C3F(1) mice received 125 ppm in feed to allow for study of mice with serum concentrations of oxazepam similar to those achieved in humans taking a therapeutic dose. At 57 weeks, treatment-related mortality of exposed SW mice caused the study to be terminated. Enhanced systemic amyloidosis contributing to heart failure was considered the principal cause of death. Hepatocellular adenomas and carcinomas were increased in exposed SW mice. Survival of B6C3F(1) mice receiving 2500 and 5000 ppm oxazepam was also lower than that of controls. Early deaths were due to increased incidences of hepatoblastoma and hepatocellular carcinoma, and nearly all mice receiving 2500 or 5000 ppm developed hepatocellular neoplasia. An increase in follicular cell hyperplasia of the thyroid gland occurred in all exposed groups of B6C3F(1) mice, and thyroid gland follicular cell adenoma was increased in exposed females. Further studies of the capacity of oxazepam to induce liver cell mitogenesis and an evaluation of the frequency of activated H- and K-ras oncogenes in the liver tumors of B6C3F(1) mice has shown that many of the neoplastic and nonneoplastic responses of mice to oxazepam resemble those observed with phenobarbital. (C) 1994 Society of Toxicology. C1 BATTELLE MEM LABS,COLUMBUS,OH. RP BUCHER, JR (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 74 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1994 VL 23 IS 2 BP 280 EP 297 DI 10.1006/faat.1994.1106 PG 18 WC Toxicology SC Toxicology GA PD169 UT WOS:A1994PD16900014 PM 7982536 ER PT J AU FRIZELL, E ABRAHAM, A DOOLITTLE, M BASHEY, R KRESINA, T VANTHIEL, D ZERN, MA AF FRIZELL, E ABRAHAM, A DOOLITTLE, M BASHEY, R KRESINA, T VANTHIEL, D ZERN, MA TI FK506 ENHANCES FIBROGENESIS IN IN-VITRO AND IN-VIVO MODELS OF LIVER FIBROSIS IN RATS SO GASTROENTEROLOGY LA English DT Article ID IMMUNOSUPPRESSANT FK506; INDUCED HEPATITIS; GAMMA-INTERFERON; CELL ACTIVATION; CDNA CLONING; FK-506; EXPRESSION; GENES; CYCLOPHILIN; COMPLEXES C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,PHILADELPHIA,PA 19107. ROGER WILLIAMS MED CTR,DEPT MED,PROVIDENCE,RI. BROWN UNIV,PROVIDENCE,RI. NIDDKD,BETHESDA,MD. BAPTIST MED CTR,OKLAHOMA TRANSPLANTAT INST,DEPT SURG,OKLAHOMA CITY,OK 73112. FU NIAAA NIH HHS [AA06386]; NIDDK NIH HHS [DK41875] NR 41 TC 31 Z9 31 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 AUG PY 1994 VL 107 IS 2 BP 492 EP 498 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PA131 UT WOS:A1994PA13100021 PM 7518783 ER PT J AU CELI, FS TANNER, K ROTH, AK ROTH, AE SHULDINER, AR AF CELI, FS TANNER, K ROTH, AK ROTH, AE SHULDINER, AR TI THE 2 NONALLELIC XENOPUS INSULIN GENES ARE EXPRESSED COORDINATELY IN THE ADULT PANCREAS SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; II GENE; PREPROINSULIN GENES; NEURITE FORMATION; ENDOCRINE-CELLS; MESSENGER-RNAS; PROTEIN ISL-1; RAT; NEURONS; LAEVIS AB We have previously shown that the two nonallelic insulin genes in Xenopus laevis are expressed differentially during neurulation in prepancreatic embryos (Shuldiner et al., 1991, Proc. Natl. Acad. Sci. USA 88, 7679-7683). We now examine pancreatic expression with alterations in ambient temperature, glucose administration, fasting and feeding, somatostatin analog treatment, as well as during postmetamorphic growth. Insulin I and II mRNAs were quantitated by slot blot hybridization with specific probes and were expressed as the number of copies (x10(8)) per 5 mu g total RNA +/- SEM. Frogs maintained at 12 degrees showed no significant changes when compared to frogs maintained at 20 degrees. There was a coordinate decrease in insulin I and II mRNA levels in frogs maintained at 29 degrees (Ins I-20, 3.41 +/- 0.34 vs Ins I-29, 2.39 +/- 0.17; Ins II20, 2.59 +/- 0.36 vs Ins II29, 1.67 +/- 0.09; P < 0.05). When compared to fasting animals, both insulin I and II mRNA levels decreased slightly in frogs given repeated intraperitoneal injections of glucose and in those fed ad libitum; there were no changes after a single dose of glucose or in frogs given somatostatin. When compared to young frogs (6 to 24 months), older frogs (36 months) had higher insulin I and II mRNA levels (e.g., Ins I-6mo, 2.14 +/- 0.15 vs Ins I-36mo, 3.68 +/- 0.43; Ins II6mo, 1.21 +/- 0.06 vs Ins II36mo, 3.26 +/- 0.38; P < 0.05). Further, there was a modest reduction in the percentage of insulin I mRNA with aging (e.g., 6 months 63.6 +/- 3.1% vs 36 months 53.9 +/- 2.7%; P < 0.05). We conclude that the two nonallelic insulin genes are regulated coordinately in adult pancreas and suggest that the mechanisms responsible for differential insulin gene expression during neurulation in prepancreatic embryos are distinct from those that regulate coordinate expression in the adult pancreas. (C) 1994 Academic Press, Inc. C1 NIA,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. RP CELI, FS (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224, USA. RI annie, annie/N-4756-2014 NR 38 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD AUG PY 1994 VL 95 IS 2 BP 169 EP 177 DI 10.1006/gcen.1994.1114 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PA125 UT WOS:A1994PA12500002 PM 7525401 ER PT J AU THOMPSON, FH LIU, Y EMERSON, J WEINSTEIN, R MAKAR, R TRENT, JM TAETLE, R ALBERTS, DS AF THOMPSON, FH LIU, Y EMERSON, J WEINSTEIN, R MAKAR, R TRENT, JM TAETLE, R ALBERTS, DS TI SIMPLE NUMERIC ABNORMALITIES AS PRIMARY KARYOTYPE CHANGES IN OVARIAN-CARCINOMA SO GENES CHROMOSOMES & CANCER LA English DT Article ID CHROMOSOME-ABERRATIONS; TUMORS AB Simple near-diploid karyotypes in ovarian cancer may indicate either primary alterations related to tumor pathogenesis or abnormalities associated with early tumor progression. We have identified a series of 13 epithelial ovarian tumors with very simple karyotypes. Specifically, these karyotypes were near-diploid and displayed numeric abnormalities alone or combined with one or two structural alterations. The present series includes samples from 10 patients with newly diagnosed adenocarcinomas and 3 patients having borderline malignancies. Recurrent numeric abnormalities were identified and included 9/13 cases (69%) with + 12, eight cases (62%) with + 8, five cases (38%) with + 7, three cases (23%) each with + 3 or + 5, and two cases (15%) with -X. Five cases in this series displayed certain numeric abnormalities (+ 12, + 7, and -X) as the sole anomalies, thereby qualifying as primary karyotype changes. Of the 6 cases with structural abnormalities, 4 involved chromosome 19, 2 involved chromosome I, and the remaining abnormalities or translocation partners involved other chromosomes. These findings indicate that some numeric abnormalities are primary karyotype alterations in patients with malignant epithelial ovarian rumors and that chromosome 19 may be preferrentially involved in structural rearrangements during early tumor progression. Genes Chromosom Cancer 10:262-266 (1994). (C) 1994 Wiley-Liss, Inc. C1 UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ 85721. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP THOMPSON, FH (reprint author), UNIV ARIZONA,ARIZONA CANC CTR,1515 N CAMPBELL AVE,TUCSON,AZ 85724, USA. FU NCI NIH HHS [NCI CA-41183] NR 24 TC 39 Z9 39 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1994 VL 10 IS 4 BP 262 EP 266 DI 10.1002/gcc.2870100407 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA NW897 UT WOS:A1994NW89700006 PM 7522540 ER PT J AU GERMANN, UA SCHOENLEIN, PV ZIMONJIC, DB POPESCU, NC PASTAN, I GOTTESMAN, MM AF GERMANN, UA SCHOENLEIN, PV ZIMONJIC, DB POPESCU, NC PASTAN, I GOTTESMAN, MM TI PUTATIVE MDR-ENHANCER IS LOCATED ON HUMAN-CHROMOSOME-20 AND NOT LINKED TO THE MDRI GENE ON CHROMOSOME-7 SO GENES CHROMOSOMES & CANCER LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN GENE; CELL-LINES; HUMAN DNA; EXPRESSION; PROMOTER; LOCALIZATION; SEQUENCE; COLCHICINE; CLONING AB The physiologic expression of the human multidrug resistance MDR1 gene product P-glycoprotein is controlled in a tissue- and cell-specific manner, but the regulatory mechanisms have not been characterized in great detail. Studies by Kohno et al. [(1990) Biol Chem 265: 19690-19696] suggested that a tissue-specific enhancer element located approximately 10 kb upstream from the major MDR I transcription start site may act to increase the levels of transcription in cultured adrenal and kidney cells. Using this putative ''MDR enhancer'' as a probe, we isolated a 14 kb DNA fragment from a genomic DNA library prepared from human fetal liver. The restriction map and partial nucleotide sequence of this DNA fragment were consistent with the previously described data obtained for a similar piece of genomic DNA derived from human placenta by Kohno et al. (ibid.). pulsed-field gel electrophoresis of large genomic DNA fragments, however, showed that the DNA sequences, including the putative ''MDR enhancer,'' were not linked to the MDR1 gene. Fluorescence in situ hybridization analysis revealed that this enhancer-like element is located on chromosome 20 at band q13.1 and is, therefore, distinct from the MDR locus on chromosome 7, band q21.1. Thus, this putative regulatory element does not modulate the tissue specificity of expression of the MDR1 gene in vivo, but may play a role in the regulation of expression of another, so far unknown gene. Genes Chromosom Cancer 10:267-274 (1994). (C) 1994 Wiley-Liss, Inc. C1 NCI,BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP GERMANN, UA (reprint author), NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892, USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1994 VL 10 IS 4 BP 267 EP 274 DI 10.1002/gcc.2870100408 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA NW897 UT WOS:A1994NW89700007 PM 7522541 ER PT J AU KIRSCHNER, MA ARRIZA, JL COPELAND, NG GILBERT, DJ JENKINS, NA MAGENIS, E AMARA, SG AF KIRSCHNER, MA ARRIZA, JL COPELAND, NG GILBERT, DJ JENKINS, NA MAGENIS, E AMARA, SG TI THE MOUSE AND HUMAN EXCITATORY AMINO-ACID TRANSPORTER GENE (EAAT1) MAPS TO MOUSE CHROMOSOME-15 AND A REGION OF SYNTENIC HOMOLOGY ON HUMAN-CHROMOSOME-5 SO GENOMICS LA English DT Note ID GLUTAMATE TRANSPORTER; NERVOUS-SYSTEM; SPINAL-CORD; LINKAGE MAP; RAT-BRAIN; SHORT ARM; EXPRESSION; DISEASE; CLONING; MUTANT AB The gene for human excitatory amino acid transporter (EAAT1) was localized to the distal region of human chromosome 5p13 by in situ hybridization of metaphase chromosome spreads. Interspecific backcross analysis identified the mouse Eaat1 locus in a region of 5p13 homology on mouse chromosome 15. Markers that are linked with EAAT1 on both human and mouse chromosomes include the receptors for leukemia inhibitory factor, interleukin-7, and prolactin. The Eaat1 locus appears not to be linked to the epilepsy mutant stg locus, which is also on chromosome 15. The EAAT1 locus is located in a region of 5p deletions that have been associated with mental retardation and microcephaly. (C) 1994 Academic Press, Inc. C1 OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MED GENET,PORTLAND,OR 97201. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP KIRSCHNER, MA (reprint author), OREGON HLTH SCI UNIV,VOLLUM INST ADV BIOMED RES,3181 SAM JACKSON PK RD,PORTLAND,OR 97201, USA. FU NINDS NIH HHS [NS 01342]; PHS HHS [MCH 000920, N01-C0-74101] NR 22 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 1994 VL 22 IS 3 BP 631 EP 633 DI 10.1006/geno.1994.1437 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PC816 UT WOS:A1994PC81600016 PM 8001975 ER PT J AU COPELAND, NG JENKINS, NA HARVEY, RP AF COPELAND, NG JENKINS, NA HARVEY, RP TI THE MURINE HOMEOBOX GENE-NKX2.3 AND GENE-NKX2.6 ARE LOCATED ON CHROMOSOME-19 AND CHROMOSOME-14, RESPECTIVELY SO GENOMICS LA English DT Note ID MOUSE; IDENTIFICATION; LOCALIZATION; EXPRESSION; DROSOPHILA; REGION; HEART C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3050,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 13 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 1994 VL 22 IS 3 BP 655 EP 656 DI 10.1006/geno.1994.1444 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PC816 UT WOS:A1994PC81600023 PM 8001981 ER PT J AU RILEY, MW AF RILEY, MW TI THE 1993 KENT LECTURE - AGING AND SOCIETY - PAST, PRESENT, AND FUTURE SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT 46th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 19-23, 1993 CL NEW ORLEANS, LA SP Gerontol Soc Amer RP RILEY, MW (reprint author), NIA,BETHESDA,MD 20892, USA. NR 31 TC 26 Z9 26 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1994 VL 34 IS 4 BP 436 EP 446 PG 11 WC Gerontology SC Geriatrics & Gerontology GA PB469 UT WOS:A1994PB46900001 PM 7959099 ER PT J AU DONADEL, G CALABRO, A SIGOUNAS, G HASCALL, VC NOTKINS, AL HARINDRANATH, N AF DONADEL, G CALABRO, A SIGOUNAS, G HASCALL, VC NOTKINS, AL HARINDRANATH, N TI HUMAN POLYREACTIVE AND MONOREACTIVE ANTIBODIES - EFFECT OF GLYCOSYLATION ON ANTIGEN-BINDING SO GLYCOBIOLOGY LA English DT Article DE ANTIGEN BINDING; GLYCOSYLATION; POLYREACTIVE ANTIBODIES ID B-CELL REPERTOIRE; MONOCLONAL AUTOANTIBODIES; HIGH-AFFINITY; RHEUMATOID-ARTHRITIS; POLYACRYLAMIDE GELS; CONSTANT REGION; MULTIPLE ORGANS; CLONAL ANALYSIS; RABIES VIRUS; HUMAN-IGM AB The present experiments were initiated to determine whether the carbohydrate portions of antibody molecules contribute to polyreactivity. Cell lines making human monoclonal polyreactive or monoreactive antibodies of the imnunoglobulin (lg) M, IgG and IgA isotypes were treated with tunicamycin to block N-linked glycosylation of the proteins. Analysis of the secreted native and non-glycosylated proteins revealed a > 95% inhibition of [H-3]mannose incorporation. Electrophoresis on sodium dodecyl sulphate-polyacrylamide gels of the proteins from tunicamycin-treated cells showed increased mobility and the absence of [H-3]mannose incorporation of the immunoglobulin heavy chains, consistent with the lack of glycosylation. The native and non-glycosylated antibodies were then tested for their ability to bind different antigens. Despite the lack of glycosylation, both polyreactive and monoreactive antibodies bound to antigens with little if any loss of reactivity or specificity. It is concluded that the carbohydrate moieties do not contribute significantly to polyreactivity. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP DONADEL, G (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 121,BETHESDA,MD 20892, USA. NR 41 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 1994 VL 4 IS 4 BP 491 EP 496 DI 10.1093/glycob/4.4.491 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF238 UT WOS:A1994PF23800013 PM 7827411 ER PT J AU BALAJI, PV QASBA, PK RAO, VSR AF BALAJI, PV QASBA, PK RAO, VSR TI MOLECULAR-DYNAMICS SIMULATIONS OF HIGH-MANNOSE OLIGOSACCHARIDES SO GLYCOBIOLOGY LA English DT Article DE CARBOHYDRATES; CONFORMATION; GLYCOSIDASE INHIBITORS; MANNOSIDASE; OLIGOSACCHARIDE PROCESSING ID N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; LIVER GOLGI MEMBRANES; MONOFUCOSYLATED BIANTENNARY GLYCAN; COMPLEX-TYPE OLIGOSACCHARIDES; RAT-LIVER; CONFORMATIONAL-ANALYSIS; TRIMMING MAN9-MANNOSIDASE; TETRASACCHARIDE NYSTOSE; ACETYLGLUCOSAMINIDASE-H AB Conformations of several high-mannose-type oligosaccharides that are generated during the biosynthetic degradation of Man(9)GlcNAc(2) to Man(5)GlcNAc(2) have been studied by molecular dynamics (MD). Simulations were performed on NCI-FCRDC's Cray Y-MP 8D/8128 supercomputer using Biosym's CVFF force field for 1000 ps with different initial conformations. The conformations of the two alpha 1,3- and the two alpha 1,6-linkages in each oligomannose were different, suggesting that deriving oligosaccharide conformations based on the conformational preferences of the constituent disaccharide fragments will not always yield correct results. Unlike other oligomannoses, Man(9)GlcNAc(2) appears to take more than one distinct conformation around the core alpha 1,6-linkage. These various conformations may play an important role in determining the processing pathways. Using the data on the preferred conformations of these oligomannoses and the available experimental results, possible pathways for processing Man(9)GlcNAc(2) to Man(5)GlcNAc(2) by alpha 1,2-linkage-specific mannosidases have been proposed. Conformational analysis of Man(5)GlcNAc(2) indicates that the addition of beta 1,2-GlcNAc to the alpha 1,3-linked core mannose, besides serving as a prerequisite for mannosidase II action as suggested earlier, may also prevent the removal of alpha 1,3-mannose. The MD simulations also suggest that the processing of the precursor oligosaccharide during Asn-linked complex and hybrid glycan biosynthesis proceeds in a well-defined pathway involving more than one alpha 1,2-linkage-specific mannosidase. Knowledge of the conformation of the processing intermediates obtained from the present study can be used to design highly specific substrate analogues to inhibit a particular mannosidase, thereby blocking one processing pathway without interfering with the others. RP BALAJI, PV (reprint author), NCI, MATH BIOL LAB, BLDG PK 5, ROOM 410, 9000 ROCKVILLE PL, BETHESDA, MD 20892 USA. NR 65 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 1994 VL 4 IS 4 BP 497 EP 515 DI 10.1093/glycob/4.4.497 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF238 UT WOS:A1994PF23800014 PM 7827412 ER PT J AU THOTAKURA, NR SZKUDLINSKI, MW WEINTRAUB, BD AF THOTAKURA, NR SZKUDLINSKI, MW WEINTRAUB, BD TI STRUCTURE-FUNCTION STUDIES OF OLIGOSACCHARIDES OF RECOMBINANT HUMAN THYROTROPIN BY SEQUENTIAL DEGLYCOSYLATION AND RESIALYLATION SO GLYCOBIOLOGY LA English DT Article DE DEGLYCOSYLATION; EXOGLYCOSIDASES; OLIGOSACCHARIDES; RECOMBINANT THYROTROPIN; SIALYLTRANSFERASES ID HUMAN CHORIONIC-GONADOTROPIN; THYROID-STIMULATING HORMONE; HAMSTER OVARY CELLS; GLYCOPROTEIN HORMONES; BIOLOGICAL-ACTIVITY; SIALYLATED OLIGOSACCHARIDES; METABOLIC-CLEARANCE; GALACTOSE RESIDUES; CARBOHYDRATE; BIOACTIVITY AB Recombinant human thyrotrophin (rhTSH) contains oligosaccharides terminating in -galactose-siahc acid, and had lower metabolic clearance and higher in vivo bioactivity compared to pituitary hTSH, which has oligosaccharides terminating predominantly in -N-acetylgalactosamine-sulphate. Previous studies using complete removal of the oligosaccharide chains showed an important role for the carbohydrate in the biological activity of the hormone. In the present study, we have determined the contribution of the individual monosaccharides to hormonal activity by sequential deglycosylation of rhTSH using exoglycosidases. We have also investigated the effect of resialylation of desialylated rhTSH using sialyltransferases. Sequential removal of sialic acid, galactose or N-acetylglucosamine resulted in a > 10-fold increase in the in vitro bioactivity of rhTSH. The metabolic clearance of the derivatives was faster than that of intact hormone, but agalacto-rhTSH was cleared slower than asialo-rhTSH. However, the in vivo bioactivity decreased progressively with each monosaccharide removal. The increased cyclic AMP-stimulating activity, increased metabolic clearance and the decreased in vivo biologic activity were all reversed by resialylation of the terminal galactose residues. These results indicate that the in vitro, as well as the in vivo, bioactivities of rhTSH are modulated by terminal sialylation. The effects of sequential deglycosylation on the in vitro activity of rhTSH are different from those reported earlier for human chorionic gonadotrophin. Thus, modification of the oligosaccharides by glycosidases and glycosyltransferases can be used as a powerful tool to delineate the function of carbohydrate in glycoproteins and to engineer more potent hormone analogues with a longer half-life and/or higher bioactivity. C1 NIDDK,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 34 TC 21 Z9 21 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 1994 VL 4 IS 4 BP 525 EP 533 DI 10.1093/glycob/4.4.525 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF238 UT WOS:A1994PF23800016 PM 7827414 ER PT J AU LI, HS NIEDZIELSKI, AS BEISEL, KW HIEL, H WENTHOLD, RJ MORLEY, BJ AF LI, HS NIEDZIELSKI, AS BEISEL, KW HIEL, H WENTHOLD, RJ MORLEY, BJ TI IDENTIFICATION OF A GLUTAMATE/ASPARTATE TRANSPORTER IN THE RAT COCHLEA SO HEARING RESEARCH LA English DT Article DE GLUTAMATE TRANSPORTER; COCHLEA; CDNA; POLYMERASE CHAIN REACTION ID GUINEA-PIG COCHLEA; POTASSIUM-INDUCED RELEASE; SPIRAL GANGLION NEURONS; RECEPTOR MESSENGER-RNAS; AMINO-ACID CONTENT; KAINIC ACID; AUDITORY-NERVE; HAIR-CELLS; GLUTAMATE TRANSPORTER; SOUND STIMULATION AB The neurotransmitter at the synapses between hair cells and spiral ganglion cells in the cochlea is probably L-glutamate or a similar excitatory amino acid. Glutamate uptake by nerve terminals and glial cells is an important component of neurotransmission at glutamatergic synapses of the central nervous system, for providing a reservoir of transmitter or transmitter precursors and the termination of the released glutamate. Hair cell synapses are not surrounded by glial cells, therefore, the uptake mechanism for glutamate in the cochlea may be unique, cDNA was synthesized from total RNA isolated separately from the rat organ of Corti, spiral ganglia, and lateral wall tissues. The expression of a glutamate/aspartate transporter (GLAST) was detected by DNA amplification with the polymerase chain reaction. The other two members of glutamate transporters in this family were not detected by this method. A partial cDNA encoding to GLAST was identified by sequence analysis in a rat cochlear cDNA library. Data concerning the expression and the molecular structure of the glutamate transporter GLAST in the cochlea may provide important information regarding the neurotransmission process at the hair cell-afferent synapses. C1 BOYS TOWN NATL RES HOSP,OMAHA,NE 68131. NATL INST DEAFNESS & COMMUN DISORDERS,NEUROCHEM LAB,BETHESDA,MD. FU NIDCD NIH HHS [DC00215, DC00982] NR 62 TC 47 Z9 50 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 AUG PY 1994 VL 78 IS 2 BP 235 EP 242 DI 10.1016/0378-5955(94)90029-9 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA PB851 UT WOS:A1994PB85100012 PM 7527019 ER PT J AU BASILE, AS JONES, EA AF BASILE, AS JONES, EA TI THE INVOLVEMENT OF BENZODIAZEPINE RECEPTOR LIGANDS IN HEPATIC-ENCEPHALOPATHY SO HEPATOLOGY LA English DT Letter ID BRAIN CONCENTRATIONS; RABBIT MODEL; RATS; GABA; FAILURE; BINDING C1 DEPT HLTH,LONDON SW8 5NG,ENGLAND. RP BASILE, AS (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,BETHESDA,MD 20892, USA. NR 13 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1994 VL 20 IS 2 BP 541 EP 542 DI 10.1016/0270-9139(94)90217-8 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PA130 UT WOS:A1994PA13000038 PM 8045517 ER PT J AU HARRISON, LD KENNEDY, NJ AF HARRISON, LD KENNEDY, NJ TI DRUG-USE IN THE UNITED-STATES-MEXICO BORDER AREA - IS THERE AND EPIDEMIC WAITING TO HAPPEN SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES LA English DT Article ID AMERICAN AB This article examines the prevalence of illicit drug, alcohol and cigarette use along the US. side of the international border with Mexico. The National Household Survey on Drug Abuse (NHSDA) provides unique coverage of the Mexico border area, based on its design that oversamples Hispanics in areas where they tend to be concentrated. The prevalence of drug use along the border is very similar to that found throughout the remainder of the United States. However Hispanics residing near the border exhibit lower prevalance rates for most classes of drugs than their counterparts in the remainder of the United States. Conversely, Hispanic youth report comparatively higher prevalence rates. These findings imply that we must remain vigilant in our prevention efforts in the border area to keep drug use from escalating. RP HARRISON, LD (reprint author), NIDA,LEXINGTON,KY 40583, USA. NR 16 TC 10 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0739-9863 J9 HISPANIC J BEHAV SCI JI Hisp. J. Behav. Sci. PD AUG PY 1994 VL 16 IS 3 BP 281 EP 295 DI 10.1177/07399863940163006 PG 15 WC Psychology, Multidisciplinary SC Psychology GA PA113 UT WOS:A1994PA11300006 ER PT J AU VINORES, SA HERMAN, MM KATSETOS, CD MAY, EE FRANKFURTER, A AF VINORES, SA HERMAN, MM KATSETOS, CD MAY, EE FRANKFURTER, A TI NEURON-ASSOCIATED CLASS-III BETA-TUBULIN, TAU, AND MAP2 IN THE D-283 MED CELL-LINE AND IN PRIMARY EXPLANTS OF HUMAN MEDULLOBLASTOMA SO HISTOCHEMICAL JOURNAL LA English DT Article ID ORGAN-CULTURE SYSTEMS; FIBRILLARY ACIDIC PROTEIN; MURINE OVARIAN TERATOMA; HUMAN CEREBELLAR CORTEX; RETINAL S-ANTIGEN; PRIMITIVE NEUROEPITHELIUM; MICROSCOPY OBSERVATIONS; COMPARATIVE IMMUNOBLOT; NEUROFILAMENT PROTEIN; MICROTUBULE PROTEINS AB The D283 Med human medulloblastoma cell line and primary explants of five surgically excised medulloblastomas were cultured using a three-dimensional Gelfoam matrix system. The cultures were evaluated immunohistochemically for a series of antigenic determinants associated with neuronal or glial differentiation. Focal immunolocalization of class III beta-tubulin, micro tubule-associated protein 2 (MAP2), and to a lesser degree tau, was demonstrated in all cultures. Class III beta-tubulin isotype, MAP2, and tau protein were also detected by immunoblot in Gelfoam matrix cultures, monolayer cultures, and suspension cultures of D283 Med cells. Staining for neurofilament protein epitopes was highly variable, even among different cultures derived from the same original tumour, but time-dependent changes in neurofilament protein, which may have reflected neuronal differentiation, were not consistently shown. Widespread gamma-enolase and focal synaptophysin reactivities were visualized in all cultures, but no S-antigen staining was detected. Leu 7 labelling was variably present in half of the cultures of D283 Med cells, but was more abundant in explants derived from four of the five original tumours. Vimentin was consistently found in D283 Med cultures at all time points. No immunoreactivity for glial fibrillary acidic protein was detected in the D283 Med cell line. Conversely, staining for this protein was demonstrated in scattered astrocytic cells in the surgical specimens of all five medulloblastomas. Concomitant with increased time in culture, three of the primary rumours displayed increased numbers of glial fibrillary acidic protein-positive cells when cultured in the Gelfoam system, but the other two rumours had a minimal astrocytic component. Collectively, our findings indicate that the D283 Med cell line and explants of five primary medulloblastomas exhibit a chiefly neuroblastic phenotype. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,IRP,CLIN BRAIN DISORDERS BRANCH,NEUROPATHOL SECT,WASHINGTON,DC 20032. HAHNEMANN UNIV,DEPT PATHOL,NEUROPATHOL LAB,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT NEUROL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT NEUROSURG,PHILADELPHIA,PA 19102. PK VIEW HOSP,CENTENNIAL MED CTR,DEPT PATHOL,NASHVILLE,TN 37203. UNIV VIRGINIA,DEPT BIOL,CHARLOTTESVILLE,VA 22908. RP VINORES, SA (reprint author), JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,600 N WOLFE ST,825 MAUMENEE,BALTIMORE,MD 21287, USA. FU NCI NIH HHS [CA 31271]; NEI NIH HHS [EY 10017] NR 39 TC 17 Z9 17 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD AUG PY 1994 VL 26 IS 8 BP 678 EP 685 DI 10.1007/BF00158293 PG 8 WC Cell Biology SC Cell Biology GA PD640 UT WOS:A1994PD64000008 PM 7527016 ER PT J AU YAKAR, S DOMENE, H MEIDAN, R CASSORLA, F GILAD, I KOCH, I LARON, Z ROBERTS, CT LEROITH, D ESHET, R AF YAKAR, S DOMENE, H MEIDAN, R CASSORLA, F GILAD, I KOCH, I LARON, Z ROBERTS, CT LEROITH, D ESHET, R TI GROWTH-HORMONE (GH) STIMULATES INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF-BINDING PROTEIN (IGFBP)-2 GENE-EXPRESSION IN SPLEENS OF JUVENILE RATS SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE GROWTH HORMONE; IGF-I; GENE EXPRESSION; SPLEEN ID TRANSGENIC MICE; ORGAN GROWTH; HYPOPHYSECTOMY AB Growth and development of the spleen involves the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To evaluate the molecular mechanism of these effects we studied the effect of hypophysectomy (Hx) and GH replacement therapy an the expression of IGF-I, the IGF-I receptor and IGF-binding protein-2 (IGFBP-2) in juvenile rats. Hx resulted in a 30% reduction in body weight. GH replacement therapy for seven days partially prevented these effects. IGF-I mRNA levels were reduced 30% by Hx, IGFBP-2 mRNA levels fell 50% whereas IGF-I receptor mRNA levels were unaffected. GH therapy prevented the reduction in IGF-I and IGFBP-2 mRNA levels. These results suggest that the GH effect on splenic growth and development is via local (paracrine) IGF-I expression, in addition to any effect by circulating (endocrine) IGF-I. C1 NIDDK, DIABET BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. CHILDRENS MED CTR ISRAEL, ENDOCRINOL & DIABET RES UNIT, PETAH TIQWA, ISRAEL. TEL AVIV UNIV, SACKLER FAC MED, IL-69978 TEL AVIV, ISRAEL. WEIZMANN INST SCI, DEPT HORMONE RES, IL-76100 REHOVOT, ISRAEL. OI Roberts, Charles/0000-0003-1756-5772 NR 19 TC 11 Z9 11 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD AUG PY 1994 VL 26 IS 8 BP 363 EP 366 DI 10.1055/s-2007-1001707 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD328 UT WOS:A1994PD32800003 PM 7528707 ER PT J AU DROPULIC, B JEANG, KT AF DROPULIC, B JEANG, KT TI GENE-THERAPY FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - GENETIC ANTIVIRAL STRATEGIES AND TARGETS FOR INTERVENTION SO HUMAN GENE THERAPY LA English DT Review ID LONG TERMINAL REPEAT; RECOMBINANT SOLUBLE CD4; INHIBITS HIV-1 REPLICATION; HEMATOPOIETIC STEM-CELLS; AIDS-RELATED COMPLEX; RNA-BINDING PROTEIN; WILD-TYPE VIRUS; T-CELL; RETROVIRAL VECTORS; ANTISENSE OLIGODEOXYNUCLEOTIDES AB Gene therapeutic strategies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection have received increased attention due to lack of chemotherapeutic drugs of vaccines that show long-term efficacy in vivo. An emerging group, referred to here as ''genetic antivirals,'' is reviewed. Genetic antivirals are defined as DNA or RNA elements that are transferred into cells and affect their intracellular targets either directly, or after expression as RNA or proteins. They include antisense oligonucleotides, ribozymes, RNA decoys, transdominant mutants, toxins, and immunogens. They offer the possibility to target simultaneously multiple sites in the HIV genome, thereby minimizing the production of resistant viruses. We review the molecular mechanisms of genetic antivirals, their HIV molecular targets, and discuss issues concerning their application as anti-HIV agents. C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 128 TC 62 Z9 62 U1 0 U2 1 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 AUG PY 1994 VL 5 IS 8 BP 927 EP 939 DI 10.1089/hum.1994.5.8-927 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PD826 UT WOS:A1994PD82600002 PM 7948142 ER PT J AU CROSSEY, PA RICHARDS, FM FOSTER, K GREEN, JS PROWSE, A LATIF, F LERMAN, MI ZBAR, B AFFARA, NA FERGUSONSMITH, MA MAHER, ER AF CROSSEY, PA RICHARDS, FM FOSTER, K GREEN, JS PROWSE, A LATIF, F LERMAN, MI ZBAR, B AFFARA, NA FERGUSONSMITH, MA MAHER, ER TI IDENTIFICATION OF INTRAGENIC MUTATIONS IN THE VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE AND CORRELATION WITH DISEASE PHENOTYPE SO HUMAN MOLECULAR GENETICS LA English DT Article ID VONHIPPEL; CHROMOSOME-3; MARKERS; REGION; TYPE-2 AB Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal haemangioblastoma, renal cell carcinoma, phaeochromocytoma and pancreatic tumours. We have previously detected large germline deletions by Southern analysis and pulsed field gel electrophoresis in 19% and 3% of VHL patients respectively. We have now investigated 94 VHL patients without large deletions for intragenic mutations using single strand conformation polymorphism and heteroduplex analysis. Forty different mutations were identified in 55 unrelated kindreds. A wide variety of mutations were detected including missense (n = 19), nonsense (n = 6), frameshift deletions or insertions (n = 12), in frame deletions (n = 2) and a splice donor site mutation (n = 1). The two most frequent mutations, were missense mutations at codon 238 (Arg --> Gln and Arg --> Trp) and were detected in five and four unrelated kindreds, respectively. VHL disease shows marked phenotypic variability and although phaeochromocytoma occurs in only about 7% of patients, marked interfamilial differences are observed. We examined the relationship between VHL gene mutations and phenotype in 65 kindreds. Large deletions or intragenic mutations predicted to cause a truncated protein were found in 36 of 53 families without phaeochromocytoma but only two of 12 families with phaeochromocytoma (x(2) = 8.58; P < 0.01). Of 12 families with phaeochromocytoma 10 had missense mutations compared with 13 of 53 kindreds without phaeochromocytoma (x(2) = 12.33; P < 0.001). In particular, substitution of an arginine at codon 238 (Arg --> Trp or Arg --> Gin) was associated with a high risk (62%) of phaeochromocytoma. The identification of germline mutations in VHL disease has provided a molecular correlation between genotype and phenotype, and a basis for gaining an insight into the molecular basis for phenotypic variability in VHL disease. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. MEM UNIV NEWFOUNDLAND,DIV COMMUNITY MED,ST JOHNS A1B 3V6,NF,CANADA. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 24 TC 288 Z9 291 U1 3 U2 10 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1994 VL 3 IS 8 BP 1303 EP 1308 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PC827 UT WOS:A1994PC82700013 PM 7987306 ER PT J AU FUTREAL, PA COCHRAN, C ROSENTHAL, J MIKI, Y SWENSON, J HOBBS, M BENNETT, LM HAUGENSTRANO, A MARKS, J BARRETT, JC TAVTIGIAN, SV SHATTUCKEIDENS, D KAMB, A SKOLNICK, M WISEMAN, RW AF FUTREAL, PA COCHRAN, C ROSENTHAL, J MIKI, Y SWENSON, J HOBBS, M BENNETT, LM HAUGENSTRANO, A MARKS, J BARRETT, JC TAVTIGIAN, SV SHATTUCKEIDENS, D KAMB, A SKOLNICK, M WISEMAN, RW TI ISOLATION OF A DIVERGED HOMEOBOX GENE, MOX1, FROM THE BRCA1 REGION ON 17Q21 BY SOLUTION HYBRID CAPTURE SO HUMAN MOLECULAR GENETICS LA English DT Article ID OVARIAN-CANCER; FAMILIAL BREAST; CHROMOSOME-17Q; HOMEODOMAIN; SEQUENCE; TUMORS AB Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study. C1 MYRIAD GENET INC,SALT LAKE CITY,UT 84108. UNIV UTAH,MED CTR,DEPT MED INFORMAT,SALT LAKE CITY,UT 84132. UNIV UTAH,MED CTR,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. RP FUTREAL, PA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA-55914, CA-48711] NR 28 TC 40 Z9 41 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1994 VL 3 IS 8 BP 1359 EP 1364 DI 10.1093/hmg/3.8.1359 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PC827 UT WOS:A1994PC82700022 PM 7987315 ER PT J AU WENKERT, D MERENDINO, JJ SHENKER, A THAMBI, N ROBERTSON, GL MOSES, AM SPIEGEL, AM AF WENKERT, D MERENDINO, JJ SHENKER, A THAMBI, N ROBERTSON, GL MOSES, AM SPIEGEL, AM TI NOVEL MUTATIONS IN THE V2 VASOPRESSIN RECEPTOR GENE OF PATIENTS WITH X-LINKED NEPHROGENIC DIABETES-INSIPIDUS SO HUMAN MOLECULAR GENETICS LA English DT Note ID GRADIENT GEL-ELECTROPHORESIS; HUMAN ANTIDIURETIC-HORMONE; RETINITIS-PIGMENTOSA; V2-RECEPTOR GENE; RHODOPSIN GENE; IDENTIFICATION; LOCALIZATION; CLONING; FORM C1 NORTHWESTERN UNIV,SCH MED,CTR ENDOCRINOL METAB & NUTR,CHICAGO,IL 60611. SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY 13210. RP WENKERT, D (reprint author), NIDDKD,METAB DIS BRANCH,BLDG 10,ROOM 8C 101,BETHESDA,MD 20892, USA. NR 26 TC 31 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1994 VL 3 IS 8 BP 1429 EP 1430 DI 10.1093/hmg/3.8.1429 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PC827 UT WOS:A1994PC82700037 PM 7987330 ER PT J AU LANDA, BL REYNOLDS, JE BEESON, D DIEHL, SR AF LANDA, BL REYNOLDS, JE BEESON, D DIEHL, SR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE CHRND LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note ID SUBUNIT GENES C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. JOHN RADCLIFFE HOSP,INST MOLEC MED,NEUROSCI GRP,OXFORD OX3 9DU,ENGLAND. FU NIDCD NIH HHS [DC00038]; NIMHD NIH HHS [263-MD-135764] NR 4 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1994 VL 3 IS 8 BP 1445 EP 1445 DI 10.1093/hmg/3.8.1445 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PC827 UT WOS:A1994PC82700050 PM 7987343 ER PT J AU ROTH, BJ BASSER, PJ WIKSWO, JP AF ROTH, BJ BASSER, PJ WIKSWO, JP TI A THEORETICAL-MODEL FOR MAGNETOACOUSTIC IMAGING OF BIOELECTRIC CURRENTS SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID FIELD; CONDUCTION; IMPULSE; VOLUME AB A theoretical model of magneto-acoustic current imaging is derived, based on fundamental equations of continuum mechanics and electromagnetism In electrically active tissue, the interaction between an applied magnetic field, B, and action currents, J, creates a pressure distribution. In the near field limit, this pressure obeys Poisson's equation, with a source term (del x J) B. The displacement and pressure fields are calculated for a dipole (q) oriented either parallel or perpendicular to the applied magnetic field (B), at the center of an elastic, conducting sphere (radius a, shear modulus G). Surface displacements are on the order of qB/(4 pi Ga), which is about 1 nm for typical biological parameters. If the applied magnetic field is changing with time, eddy currents induced in the tissue may be larger than the action currents themselves. The frequency of the pressure and displacement arising from these eddy currents, however, is twice the frequency of the applied magnetic field, so it may be possible to eliminate this artifact by filtering or lock-in techniques. Magneto-acoustic and biomagnetic measurements both image del x J in a similar may, although magneto-acoustic current imaging has the disadvantage that acoustic properties vary among tissues to a greater degree than do magnetic properties. C1 VANDERBILT UNIV,DEPT PHYS & ASTRON,LIVING STATE PHYS GRP,NASHVILLE,TN 37235. RP ROTH, BJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,MECH ENGN SECT,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008; Basser, Peter/H-5477-2011 NR 22 TC 53 Z9 60 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 1994 VL 41 IS 8 BP 723 EP 728 DI 10.1109/10.310087 PG 6 WC Engineering, Biomedical SC Engineering GA PC838 UT WOS:A1994PC83800002 PM 7927394 ER PT J AU HENKART, PA AF HENKART, PA TI LYMPHOCYTE-MEDIATED CYTOTOXICITY - 2 PATHWAYS AND MULTIPLE EFFECTOR MOLECULES SO IMMUNITY LA English DT Article ID ANTIGEN; CELLS; MICE RP HENKART, PA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 25 TC 346 Z9 348 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1994 VL 1 IS 5 BP 343 EP 346 DI 10.1016/1074-7613(94)90063-9 PG 4 WC Immunology SC Immunology GA PK168 UT WOS:A1994PK16800001 PM 7882166 ER PT J AU PANTALEO, G GRAZIOSI, C DEMAREST, JF COHEN, OJ VACCAREZZA, M GANTT, K MUROCACHO, C FAUCI, AS AF PANTALEO, G GRAZIOSI, C DEMAREST, JF COHEN, OJ VACCAREZZA, M GANTT, K MUROCACHO, C FAUCI, AS TI ROLE OF LYMPHOID ORGANS IN THE PATHOGENESIS OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION SO IMMUNOLOGICAL REVIEWS LA English DT Review ID FOLLICULAR DENDRITIC CELLS; PERSISTENT GENERALIZED LYMPHADENOPATHY; PRIMARY MONONUCLEAR PHAGOCYTES; CD3/T-CELL RECEPTOR COMPLEX; IMMUNE-SYSTEM ACTIVATION; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; GROWTH-FACTOR-BETA; T-CELLS; IMMUNOPATHOGENIC MECHANISMS RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 11B-13,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 79 TC 147 Z9 149 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 1994 VL 140 BP 105 EP 130 DI 10.1111/j.1600-065X.1994.tb00867.x PG 26 WC Immunology SC Immunology GA PJ186 UT WOS:A1994PJ18600005 PM 7821924 ER PT J AU BAIBAKOV, BA CHIPISHEVA, TA GUELSTEIN, VI ERMILOVA, VD POLEVAYA, EB VASILIEV, JM MARGOLIS, LB AF BAIBAKOV, BA CHIPISHEVA, TA GUELSTEIN, VI ERMILOVA, VD POLEVAYA, EB VASILIEV, JM MARGOLIS, LB TI ORGANOTYPIC GROWTH AND DIFFERENTIATION OF HUMAN MAMMARY-GLAND IN SPONGE-GEL MATRIX SUPPORTED HISTOCULTURE SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE HISTOCULTURE; MAMMARY GLAND; DIFFERENTIATION; KERATIN; EPITHELIUM ID BASEMENT-MEMBRANE; CELLS; EXPRESSION; BREAST; KERATIN-17; EPITHELIA; PATTERNS; TUMORS AB Blocks of breast tissue obtained during radical mastectomies from 23 patients with mammary gland carcinomas were used for cultivation in native-state, gel-supported histocultures. We show that the human mammary gland can be successfully maintained in this system so that normal epithelial breast structures proliferate and undergo differentiation for several weeks and a well-developed system of ducts and lobules is formed. Using antibodies to individual keratins 17 and 8 we have shown for the first time that ducts and alveoles developing in vitro undergo differentiation into the lining epithelium and myoepithelium in the same way as mammary gland epithelium in vivo. Growth of epithelial structures in vitro is also accompanied by the development of continuous basal membrane. C1 NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. MOSCOW MV LOMONOSOV STATE UNIV, BELOZERSKY INST PHYS CHEM BIOL, MOSCOW 119899, RUSSIA. RUSSIAN ACAD MED SCI, RES CTR, MOSCOW, RUSSIA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD AUG PY 1994 VL 30A IS 8 BP 490 EP 495 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA NY677 UT WOS:A1994NY67700004 ER PT J AU LEAK, LV JONES, M AF LEAK, LV JONES, M TI LYMPHANGIOGENESIS IN-VITRO - FORMATION OF LYMPHATIC CAPILLARY-LIKE CHANNELS FROM CONFLUENT MONOLAYERS OF LYMPHATIC ENDOTHELIAL-CELLS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE LYMPHANGIOGENESIS; LYMPHATIC ENDOTHELIUM; EXTRACELLULAR MATRIX ID ANGIOGENESIS INVITRO; INTRAPERITONEAL STIMULATION; DIFFERENTIATION; LAMININ; SARCOMA; GROWTH; MATRIX AB Lymphatic endothelial cells grown long term in culture form lymphatic capillarylike tubes. Examination by light and transmission electron microscopy showed that these structures were closed loops composed of one to several cells connected by intercellular junction to form a luminal space. This first demonstration of lymphangiogenesis in confluent monolayer cultures of lymphatic endothelial cells (a) showed that collagen type I accelerated lymphatic capillary tube formation, whereas fibronectin and matrigel had no effect; b) provided a model to study lymphatic endothelial cell function and differentiation; and c) offered a possibility to distinguish differences between the process of lymphangiogenesis and angiogenesis by testing various factors and conditions that effect endothelial cell behavior. C1 NHLBI, ANIM MED & SURG LAB, BETHESDA, MD 20892 USA. RP LEAK, LV (reprint author), HOWARD UNIV, COLL MED, DEPT ANAT, ERNEST EVERETT JUST LAB CELLULAR BIOL, WASHINGTON, DC 20059 USA. NR 25 TC 31 Z9 31 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD AUG PY 1994 VL 30A IS 8 BP 512 EP 518 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA NY677 UT WOS:A1994NY67700007 ER PT J AU NEWBOLD, RR HANSON, RB JEFFERSON, WN AF NEWBOLD, RR HANSON, RB JEFFERSON, WN TI IMMATURE MOUSE UTERINE TISSUE IN ORGAN-CULTURE - ESTROGEN-INDUCED GROWTH, MORPHOLOGY AND BIOCHEMICAL PARAMETERS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE UTERUS; ESTROGENIC RESPONSES; LACTOFERRIN; IN VITRO; ORGAN CULTURE; DIETHYLSTILBESTROL; DES ID MESSENGER-RIBONUCLEIC-ACID; LUMINAL EPITHELIAL-CELLS; GENITAL-TRACT; MOLECULAR DIFFERENTIATION; PRENATAL EXPOSURE; REPRODUCTIVE-TRACT; ENDOMETRIAL CELLS; PROTEIN-SYNTHESIS; GENE-EXPRESSION; DIETHYLSTILBESTROL AB Although estrogens have been shown to stimulate a variety of morphologic and biochemical changes in the uterus in vivo, no clear consistent demonstration of similar responses in vitro have been made; thus, a defined organ culture system using the immature mouse uterus was established to study the possibility of demonstrating estrogenic responses in vitro. Uterine tissue from immature outbred mice (17 to 24 days of age) were cut crosswise in 1-mm(3) coins and cultured in a defined medium in the absence of serum, phenol red, or growth factor supplements. Diethylstilbestrol (DES), a synthetic estrogen, was added to the media at doses ranging from 1 to 100 ng/ml. The effect of DES on uterine cell proliferation was assessed by morphologic changes in uterine epithelial and stromal cells, increase in number of epithelial cells per unit basement membrane, increase in height of luminal epithelial cells, and [H-3]thymidine incorporation. Functional changes were determined by measuring the amounts of the estrogen-inducible uterine protein, lactoferrin, that was localized in the epithelial cells and secreted into the media, and the localization of the estrogen receptor in the cultured tissues. Results indicate that under the described conditions of culture, estrogens like DES can induce morphologic and biochemical responses in the uterus that are similar to those seen in vivo. This organ culture system will aid in the investigation of various mechanisms involved in the hormonal regulation of growth and differentiation of estrogen target tissues. RP NEWBOLD, RR (reprint author), NIEHS, DIV INTRAMURAL RES, REPROD & DEV TOXICOL LAB, DEV ENDOCRINOL & PHARMACOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD AUG PY 1994 VL 30A IS 8 BP 519 EP 528 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA NY677 UT WOS:A1994NY67700008 ER PT J AU HASE, CC THAI, LS BOESMANFINKELSTEIN, M MAR, VL BURNETTE, WN KASLOW, HR STEVENS, LA MOSS, J FINKELSTEIN, RA AF HASE, CC THAI, LS BOESMANFINKELSTEIN, M MAR, VL BURNETTE, WN KASLOW, HR STEVENS, LA MOSS, J FINKELSTEIN, RA TI CONSTRUCTION AND CHARACTERIZATION OF RECOMBINANT VIBRIO-CHOLERAE STRAINS PRODUCING INACTIVE CHOLERA-TOXIN ANALOGS SO INFECTION AND IMMUNITY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; NUCLEOTIDE-SEQUENCE ANALYSIS; HEAT-LABILE ENTEROTOXIN; ESCHERICHIA-COLI; HEMAGGLUTININ PROTEASE; VACCINE DEVELOPMENT; MOLECULAR-CLONING; A-SUBUNIT; EPITOPES; FAMILY AB The catalytic A subunit of cholera toxin (CT-A) is capable of ADP-ribosylating the guanine nucleotide-binding protein, which regulates cell adenylyl cyclase, leading to the life-threatening diarrhea of cholera. Amino acids involved in the enzymatic activity of CT-A have previously been identified. By means of site-directed mutagenesis, an analog of the CT-A subunit gene was created with codon substitutions for both Arg-7 and Glu-112, each of which has been shown to produce subunits lacking ADP-ribosyltransferase activity. The mutated gene fragment was exchanged for the wild-type copy in the previously cloned ctxAB operon from Fl Tor biotype, Ogawa serotype Vibrio cholerae strain 3083, which produces CT-2. Further, the zonula occludens toxin gene, tot, was inactivated by an insertional mutation to create the new plasmid construct pCT2*. Additionally, a DNA fragment encoding the B subunit of CT-1 (CT produced by classical biotype, Inaba serotype V. cholerae strain 569B) was exchanged for the homologous part in pCT-2*, resulting in the creation of pCT-1*. These plasmid constructs were introduced into the CT-negative V. cholerae mutant strain JBK70 (El Tor biotype, Inaba serotype); CT-A(-)B(+) derivatives CVD101 and CVD103 of classical biotype Ogawa and Inaba serotype strains 395 and 569B, respectively; Fl Tor biotype Inaba and Ogawa serotype strains C6706 and C7258, respectively, recently isolated in Peru; and O139 (synonym Bengal) strain SG25-1 from the current epidemic in India. Recombinant toxins (CT-1* and CT-2*), partially purified from culture supernatants of transformed JBK70, were shown to be inactive on mouse Y1 adrenal tumor cells and in an in vitro ADP-ribosyltransferase assay. CT-1* and CT-2* reacted with polyclonal and monoclonal antibodies against both A and B subunits of CT. The toxin analogs reacted with antibodies against CT-A and CT-B on cellulose acetate strips and in a G(M1) enzyme-linked immunosorbent assay; they reacted appropriately with B-subunit epitype-specific monoclonal antibodies in checkerboard immunoblots, and they formed precipitin bands with G(M1)-ganglioside in Ouchterlony tests. However, the reactions of the modified proteins with anti-A-subunit monoclonal antibodies were weaker than the reactions with wild-type holotoxins, V. cholerae strains carrying ctxA*, with either ctxB-1 or ctxB-2, and inactivated tot genes were created by homologous recombination, The recombinant strains and the purified toxin analogs were inactive in the infant rabbit animal model. These strains may have use as attenuated live vaccines; the analog toxins themselves might have important applications in conjugate vaccines as well as in structure-function studies. C1 UNIV MISSOURI,SCH MED,DEPT MOLEC MICROBIOL & IMMUNOL,COLUMBIA,MO 65212. AMGEN INC,THOUSAND OAKS,CA 91320. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RI Burnette, W. Neal/G-9784-2011 OI Burnette, W. Neal/0000-0002-7579-0997 FU NIAID NIH HHS [AI17312] NR 49 TC 31 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1994 VL 62 IS 8 BP 3051 EP 3057 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200002 PM 8039872 ER PT J AU RAMAKRISHNAN, L FALKOW, S AF RAMAKRISHNAN, L FALKOW, S TI MYCOBACTERIUM-MARINUM PERSISTS IN CULTURED-MAMMALIAN-CELLS IN A TEMPERATURE-RESTRICTED FASHION SO INFECTION AND IMMUNITY LA English DT Article ID TUBERCULOSIS; INFECTION; KILLER AB We have explored the relatively rapidly growing animal and human pathogen Mycobacterium marinum as an experimental model for mycobacterial pathogenesis. M. marinum, which has a lower temperature for optimal growth than does Mycobacterium tuberculosis, has a much shorter generation time and can be safely studied in ordinary laboratory facilities and examined in multiple animal infection models. We have established an in vitro essay for its interaction with eukaryotic cells and shown that it persists in these cells in a temperature-specific fashion that correlates with its ability to cause disease in vivo at lower temperatures. Additionally, preliminary evidence that M. marinum causes a chronic disease with some features resembling tuberculosis in frogs of the species Rana pipiens is presented. C1 NIAID, ROCKY MT LABS, HAMILTON, MT 59840 USA. RP STANFORD UNIV, SCH MED, DEPT IMMUNOL & MICROBIOL, FAIRCHILD D309B, STANFORD, CA 94305 USA. FU NIAID NIH HHS [AI 23945] NR 25 TC 91 Z9 93 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1994 VL 62 IS 8 BP 3222 EP 3229 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200025 PM 8039892 ER PT J AU LI, ZY MANTHEY, CL PERERA, PY SHER, A VOGEL, SN AF LI, ZY MANTHEY, CL PERERA, PY SHER, A VOGEL, SN TI TOXOPLASMA-GONDII SOLUBLE-ANTIGEN INDUCES A SUBSET OF LIPOPOLYSACCHARIDE-INDUCIBLE GENES AND TYROSINE PHOSPHOPROTEINS IN PERITONEAL-MACROPHAGES SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASES; TUMOR-NECROSIS-FACTOR; MURINE MACROPHAGES; IFN-GAMMA; INTERFERON-GAMMA; MESSENGER-RNA; LIPID-A; PHOSPHORYLATION; EXPRESSION; ENCEPHALITIS AB Previous studies have shown that macrophages play an important role in both the initiation of protective responses and the effector mechanism of immunity to Toxoplasma gondii. The purpose of this investigation was to characterize the responses of macrophages to a soluble antigen extract of T. gondii tachyzoites (STAg) in comparison with a prototypic macrophage-activating agent, lipopolysaccharide (LPS), and to determine whether STAg-induced signaling requires a functional Lps gene. Toward this end, tumor necrosis factor (TNF) secretion, a panel of six LPS-inducible genes, and protein tyrosine phosphorylation were examined to gain insights into macrophage responses to STAg. STAg stimulated both C3H/OuJ (Lps(n)) and C3H/HeJ (Lps(d)) macrophages to secrete bioactive TNF-alpha and to express a subset of LPS-inducible genes (encoding TNF-alpha, TNF receptor 2, and interleukin-1 beta). In contrast to LPS, STAg failed to stimulate Lps(n) or Lps(d) macrophages to express genes encoding IF-10, D3, or D8. STAg also induced a pattern of tyrosine phosphorylation identical to that induced by LPS; mitogen-activated protein kinase 47-kDa and 43-kDa isoforms and a 41-kDa protein of undetermined identity were inducibly phosphorylated. The ability of STAg to induce TNF-alpha, encoded by a subset of LPS-inducible genes, and tyrosine phosphoproteins was not affected by LPS inhibitors, confirming that the macrophage response to the parasite extract could not be attributed to LPS contamination. We Propose that STAg, while differing from LPS in the pattern of macrophage genes induced, may share with LPS two signaling pathways that are intact in Lds(d) macrophages. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-18797] NR 41 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1994 VL 62 IS 8 BP 3434 EP 3440 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200051 PM 8039914 ER PT J AU BYRD, LG CONRAD, JT NASH, TE AF BYRD, LG CONRAD, JT NASH, TE TI GIARDIA-LAMBLIA INFECTIONS IN ADULT MICE SO INFECTION AND IMMUNITY LA English DT Note ID PATCH LYMPHOCYTE SUBSETS; MURIS INFECTION; ANTIGENIC VARIATION; TYI-S-33 MEDIUM; ANIMAL-MODEL; CELL SUBSETS; BALB/C MICE; IMMUNOGLOBULIN; ANTIBODY; MOUSE AB An adult mouse-Giardia lamblia model was developed and used to study host-parasite interactions, including antigenic variation. The H7/1 clone of isolate GS infected mice consistently and produced infections in 14 mouse strains tested. Infection patterns were mouse strain and Giardia isolate dependent. Antigenic variation occurred in immunocompetent mice but not in mice with severe combined immunodeficiency. RP BYRD, LG (reprint author), NIH,PARASIT DIS LAB,BLDG 4,RM B1-31,BETHESDA,MD 20892, USA. NR 27 TC 65 Z9 67 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1994 VL 62 IS 8 BP 3583 EP 3585 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NY872 UT WOS:A1994NY87200075 PM 8039934 ER PT J AU UTSUYAMA, M ALBRIGHT, JW HOLMES, KL HIROKAWA, K ALBRIGHT, JF AF UTSUYAMA, M ALBRIGHT, JW HOLMES, KL HIROKAWA, K ALBRIGHT, JF TI CHANGES IN THE SUBSETS OF CD4+ T-CELLS IN TRYPANOSOMA-MUSCULI INFECTION - DELAY OF IMMUNOLOGICAL CURE IN YOUNG MICE AND THE WEAK ABILITY OF AGED MICE TO CONTROL THE INFECTION SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE AGING OF IMMUNITY; CD4(+) T CELL SUBSETS; CYTOKINES; HELPER T CELLS; MEMORY CELLS; TRYPANOSOMES ID GROWTH FACTOR-BETA; MURINE B-CELLS; LYMPHOCYTES-T; IFN-GAMMA; INTERFERON-GAMMA; SIGNAL-TRANSDUCTION; IMMUNE-SYSTEM; INTERLEUKIN-2 PRODUCTION; SECRETION; TH1 AB After a 3 week course (approximately), during which there is marked lymphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a isotype. Both the lymphoid hyperplasia and lgG2a antibody response are T-cell-dependent events and both processes appear to be defective in aged mice. The purpose of the studies reported here was to elucidate the effects of T. musculi infection on subsets of T cells for two reasons: (i) to gain insight into the probable roles of selected cytokines (IL-2, IL-4 and IFN-gamma) in facilitating the production of curative, IgG2a antibodies, and (ii) to examine the hypothesis that aging affects the competence of CD4(+) T cells to participate in immunological control of infections. The major conclusions from these studies are that: (i) T. musculi infection of mice induces rapid change in the CD4(+) T cell population toward predominance of the activated or memory (CD45RB(lo)CD44(hi)) phenotype, cells which produce IFN-gamma II-3, IL-4 and IL-5, accompanied by profound inhibition of IL-2 production, and (ii) in the old mice these changes are superimposed on the natural age-associated changes in the same direction (i.e. toward predominance of CD45RB(lo)CD44(hi) T cells). Thus, in the old animals, the combined changes of aging and infection, moving in the same direction, are devastating, resulting in the aged animals being unable, or barely able, to control infection. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT IMMUNOL & MICROBIOL,WASHINGTON,DC 20037. TOKYO METROPOLITAN GERIATR HOSP & INST GERONTOL,DEPT PATHOL,TOKYO,JAPAN. NIAID,IMMUNOPATHOL LAB,BIOL RESOURCES BRANCH,CYTOMETRY SECT,BETHESDA,MD 20892. FU NIA NIH HHS [R01 AG 06278] NR 52 TC 9 Z9 9 U1 0 U2 2 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 AUG PY 1994 VL 6 IS 8 BP 1107 EP 1115 DI 10.1093/intimm/6.8.1107 PG 9 WC Immunology SC Immunology GA PC837 UT WOS:A1994PC83700002 PM 7981140 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI TREATMENT AND DEVELOPMENTAL THERAPEUTICS OF MYCOBACTERIUM-TUBERCULOSIS INFECTIONS SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE MYCOBACTERIUM-TUBERCULOSIS; TUBERCULOSIS; MULTIDRUG THERAPY; QUINOLONES; ANTIMYCOBACTERIAL ANTIBIOTICS, IN-VITRO AND IN-VIVO EVALUATION; HOST DEFENSE; CYTOKINES; DRUG RESISTANCE ID POLYMERASE CHAIN-REACTION; IMMUNODEFICIENCY-VIRUS INFECTION; DRUG-RESISTANT TUBERCULOSIS; SHORT-COURSE CHEMOTHERAPY; TUMOR-NECROSIS-FACTOR; CULTURED HUMAN MACROPHAGES; LONG-ACTING RIFAMYCINS; T-CELL CLONES; PULMONARY TUBERCULOSIS; BACTERICIDAL ACTIVITY AB Tuberculosis still remains a serious health problem in many regions of the world, especially in developing nations. With the spread of AIDS and the increase in the number of immunocompromised patients, the problem of tuberculosis has been greatly exacerbated because of the susceptibility of such patients to mycobacteria. Currently, chemotherapy using multiple drug regimens with isoniazid, rifampin, streptomycin, pyrazinamide, and ethambutol is the recommended treatment for tuberculosis. The presence of drug resistance is still a major concern and new generations of more effective antimycobacterial agents (antibiotics, fluoroquinolone derivatives) are the subject of active investigation. The search for novel strategies to cure tuberculosis led to studies exploring the role of cytokines in host defenses and the application of adoptive immunotherapy. New and improved methodology for in vitro and in vivo screening of antimycobacterial activity has also been reported. RP STGEORGIEV, V (reprint author), NIAID,SOLAR BLDG,ROOM 4C-04,BETHESDA,MD 20892, USA. NR 169 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD AUG PY 1994 VL 4 IS 3 BP 157 EP 173 DI 10.1016/0924-8579(94)90005-1 PG 17 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA NZ479 UT WOS:A1994NZ47900005 PM 18611607 ER PT J AU SANTAMARINAFOJO, S BREWER, HB AF SANTAMARINAFOJO, S BREWER, HB TI LIPOPROTEIN-LIPASE - STRUCTURE, FUNCTION AND MECHANISM OF ACTION SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Review DE HYPERTRIGLYCERIDEMIA; CHYLOMICRONEMIA; LIPASE; STRUCTURE-FUNCTION; SITE-DIRECTED MUTAGENESIS ID SITE-DIRECTED MUTAGENESIS; INTERFACIAL ACTIVATION; HEPATIC LIPASE; MISSENSE MUTATION; PANCREATIC LIPASE; I HYPERLIPIDEMIA; TERMINAL DOMAIN; CHIMERIC LIPASE; GENE; DEFICIENCY AB Lipoprotein lipase (LPL) plays a central role in the hydrolysis of circulating triglycerides present in chylomicrons, and very low density lipoproteins. The active form of the enzyme is a non-covalent homodimer which contains multiple functional domains required for normal hydrolytic activity including a catalytic domain, as well as sites involved in co-factor, heparin and lipid binding. Recent studies involving site-directed mutagenesis, the elucidation of the three dimensional crystallographic structure of different lipases, as well as analysis of the molecular defects that result in the expression of the familial chylomicronemia syndrome have provided new insights into the structure-function relationship of LPL. As a result, our understanding of structural domains involved in catalysis, heparin, lipid binding, and enzyme-cofactor interaction as well as the mechanism of action of LPL as an acylglycerol hydrolase has been greatly enhanced. RP SANTAMARINAFOJO, S (reprint author), NHLBI,MOLEC DIS BRANCH,9000 ROCKVILLE PIKE,BLDG 10-N115,BETHESDA,MD 20892, USA. NR 39 TC 26 Z9 27 U1 0 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD AUG PY 1994 VL 24 IS 3 BP 143 EP 147 DI 10.1007/BF02592444 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD963 UT WOS:A1994PD96300004 PM 7819594 ER PT J AU AHMED, F CLEMENS, JD RAO, MR BANIK, AK AF AHMED, F CLEMENS, JD RAO, MR BANIK, AK TI FAMILY LATRINES AND PEDIATRIC SHIGELLOSIS IN RURAL BANGLADESH - BENEFIT OR RISK SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID DIARRHEAL DISEASES; YOUNG-CHILDREN; WATER; TRANSMISSION; SANITATION; IMPACT AB Background. The potential benefits of installing excreta disposal facilities on the burden of paediatric diarrhoea in less-developed settings remain controversial. We conducted a longitudinal study to evaluate whether family latrines are associated with interruption of the transmission of shigellosis to younger children in rural Bangladesh. Methods. We prospectively studied 1529 children under 5 years of age exposed to index cases of Shigella dysentery. In all 219 children with culture-proven shigellosis detected during 1 month of follow-up were compared with 1310 control children who did not develop shigellosis or Shigella-negative dysentery. Results. Overall, the presence of a family latrine appeared to be associated with a higher, not a lower, risk of paediatric shigellosis (adjusted odds ratio (OR(a)) = 1.37, 95% confidence interval (Cl): 0.99-1.89). While use of a pit or sanitary latrine revealed no evidence of a protective association (OR(a) = 0.96, 95% CI: 0.43-2.15), use of a hanging latrine in which faeces were discharged directly onto the ground or into a body of water was associated with a notable increase of risk (OR(a) = 1.42, 95% CI: 1.02-1.98, P < 0.05). Conclusions. While cautioning that installation of sanitary latrines may not be sufficient to reduce the burden of paediatric shigellosis in less-developed settings, these data suggest that eliminating unsanitary latrines constitutes a potentially important intervention in its own right in these settings. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. INT CTR DIARRHOEAL DIS RES,DHAKA 1000,BANGLADESH. NR 23 TC 15 Z9 15 U1 0 U2 3 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 AUG PY 1994 VL 23 IS 4 BP 856 EP 862 DI 10.1093/ije/23.4.856 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG751 UT WOS:A1994PG75100027 PM 8002202 ER PT J AU SAEKI, T SALOMON, D NORMANNO, N JOHNSON, GR GULLICK, WJ MANDAI, K MORIWAKI, S TAKASHIMA, S KUNIYASU, M TAHARA, E KAWAMI, H NISHIYAMA, M TOGE, T AF SAEKI, T SALOMON, D NORMANNO, N JOHNSON, GR GULLICK, WJ MANDAI, K MORIWAKI, S TAKASHIMA, S KUNIYASU, M TAHARA, E KAWAMI, H NISHIYAMA, M TOGE, T TI IMMUNOHISTOCHEMICAL DETECTION OF CRIPTO-1, AMPHIREGULIN AND TRANSFORMING GROWTH-FACTOR-ALPHA IN HUMAN GASTRIC CARCINOMAS AND INTESTINAL METAPLASIAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CRIPTO; AMPHIREGULIN; EPIDERMAL GROWTH FACTOR RECEPTOR; ERBB-2; TGF-ALPHA; P53 ID FACTOR-RECEPTOR; CELL-LINE; COLORECTAL TUMORS; EPITHELIAL-CELLS; FACTOR FAMILY; EXPRESSION; GENE; CANCER; INDUCTION; RATS AB The expression and localization of cripto-1 (CR-1), amphiregulin (AR) and transforming growth factor alpha (TGFalpha) were assessed by immunocytochemistry in 37 primary human gastric tumors, 30 noninvolved gastric mucosa samples that were adjacent to carcinoma but exhibited intestinal metaplasia and 37 adjacent, noninvolved gastric mucosa samples. Seventeen (46%), nineteen (51%) and twenty-one (57%) carcinomas showed staining for CR-1, AR and TGFalpha, respectively; whereas sixteen (53%), eight (26%) and five (17%) intestinal metaplasias were reactive with the anti-CR-1, anti-AR and anti-TGFalpha antibodies, respectively. In contrast, none of the normal, noninvolved gastric mucosa samples reacted with the TGFalpha antibody and only 1 (3%) of these samples showed weak staining with the anti-CR-1 antibody. However, 8 (21%) of the normal gastric mucosa samples showed moderate levels of staining with the AR antibody. Within the carcinomas, there was a slight trend for association between TGFalpha and CR-1 expression (p<0.05), but no correlation was found between epidermal growth factor receptor and CR-1 expression. Staining for p53 was observed in 26 (70%) of the carcinomas, 3 (10%) intestinal metaplasias and none of the gastric mucosa samples. This data demonstrate that CR-1, like TGFalpha, may be a tumor marker for a subset of gastric carcinomas in addition to being an important factor in the early stages of gastric cancer development. C1 HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL UNIT,LONDON W12 0HS,ENGLAND. HIROSHIMA UNIV,SCH MED,DEPT PATHOL,HIROSHIMA 730,JAPAN. HIROSHIMA UNIV,NUCL MED & BIOL RES INST,DEPT SURG,HIROSHIMA 730,JAPAN. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RP SAEKI, T (reprint author), NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES,ONCOGENE SECT,HORINOUCHI 13,MATSUYAMA 790,JAPAN. OI Normanno, Nicola/0000-0002-7158-2605 NR 40 TC 23 Z9 23 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 AUG PY 1994 VL 5 IS 2 BP 215 EP 223 PG 9 WC Oncology SC Oncology GA NY136 UT WOS:A1994NY13600012 PM 21559578 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI THE USE OF PROBING TOOLS BY TUFTED CAPUCHINS (CEBUS-APELLA) - EVIDENCE FOR INCREASED RIGHT-HAND PREFERENCE WITH AGE SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE CEBUS-APELLA; HAND PREFERENCE; LATERALITY; TOOL USE ID PAPIO-CYNOCEPHALUS-ANUBIS; WILD CHIMPANZEES; CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; HANDEDNESS; MONKEYS; ASSOCIATIONS; MANUFACTURE; HYPOTHESIS; PATHOLOGY AB We examined hand preference in the use of tools by tufted capuchins (Cebus apella). We presented a colony of monkeys with an enclosed container designed to accommodate the use of probing tools. Over an 8-month period, 13 monkeys used probes to extract sweet syrup from the narrow opening of the apparatus. Five monkeys exhibited bias toward use of their right hand and eight monkeys exhibited bias toward use of their left hand. Adult monkeys exhibited a greater percentage of right-hand preferent probing sequences than did juveniles. These results are consistent with hypotheses that in tasks thal involve the use of tools, nonhuman primates exhibit strong lateral asymmetries at the individual level, a moderate left-hand bias at the population level, and increased bias,with age toward use of the right hand. RP WESTERGAARD, GC (reprint author), NICHHD,NATL INST HLTH ANIM CTR,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 25 TC 21 Z9 21 U1 1 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD AUG PY 1994 VL 15 IS 4 BP 521 EP 529 DI 10.1007/BF02735969 PG 9 WC Zoology SC Zoology GA PE022 UT WOS:A1994PE02200002 ER PT J AU HUTZ, RJ AF HUTZ, RJ TI TECHNOLOGIC ADVANCES IN THE IMAGING OF OVARIAN MORPHOLOGY AND THEIR ROLES IN ASCERTAINING FOLLICULAR-GROWTH AND DEVELOPMENT IN THE RHESUS-MONKEY SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE IMAGING; RECEPTORS; ULTRASONOGRAPHY; MAGNETIC RESONANCE IMAGING (MRI); LAPAROSCOPY; RHESUS MONKEY ID GRANULOSA-CELLS; ATRESIA; ESTRADIOL-17-BETA AB Imaging follicular development has advanced notably from the invasive-laparotomy-to the relatively noninvasive-laparoscopy (making frequent observations over a single cycle possible)-to totally noninvasive approaches such as ultrasonography and magnetic resonance imaging (MRI). Now we can identify the dominant preovulatory follicle (DF) in macaques by day 6 of the menstrual cycle via laparoscopy and by day 6-8 via ultrasonography. MRI scans are remarkably correlated with histologic specimens We obtained axial, coronal, and sagittal ovarian images with MRI software. Moreover, we are discerning structure/function relationships in ovarian estrogen-receptor systems using X-ray autoradiography and immunocytochemistry. We have localized the estrogen receptor in functional corpus luteum (CL) with H-3-estradiol and in germinal epithelium and granulosa cells with monoclonal antibody to the receptor. We believe that by using a combination of the aforementioned techniques, we will be able to investigate more fully the processes of recruitment and selection of ovarian follicles. C1 UNIV WISCONSIN,NIEHS BIOMED CORE CTR,MILWAUKEE,WI 53201. MED COLL WISCONSIN,DEPT OB GYN,MILWAUKEE,WI 53226. WISCONSIN REG PRIMATE RES CTR,MADISON,WI. RP HUTZ, RJ (reprint author), UNIV WISCONSIN,DEPT BIOL SCI,LAPHAM HALL,ROOM 314,3209 N MARYLAND AVE,MILWAUKEE,WI 53201, USA. NR 28 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD AUG PY 1994 VL 15 IS 4 BP 629 EP 637 DI 10.1007/BF02735975 PG 9 WC Zoology SC Zoology GA PE022 UT WOS:A1994PE02200008 ER PT J AU OTTESEN, EA CAMPBELL, WC AF OTTESEN, EA CAMPBELL, WC TI IVERMECTIN IN HUMAN MEDICINE SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Review ID CAENORHABDITIS-ELEGANS RNA; CUTANEOUS LARVA-MIGRANS; HIGH-DOSE IVERMECTIN; BANCROFTIAN FILARIASIS; XENOPUS-OOCYTES; BINDING-SITE; EFFICACY; DIETHYLCARBAMAZINE; AVERMECTIN; INFECTION C1 DREW UNIV,INST SCI EMERITI,MADISON,NJ 07940. RP OTTESEN, EA (reprint author), NIAID,CLIN PARASITOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 91 Z9 94 U1 2 U2 17 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 AUG PY 1994 VL 34 IS 2 BP 195 EP 203 DI 10.1093/jac/34.2.195 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA PF392 UT WOS:A1994PF39200002 PM 7814280 ER PT J AU TREUTH, MS RYAN, AS PRATLEY, RE RUBIN, MA MILLER, JP NICKLAS, BJ SORKIN, J HARMAN, SM GOLDBERG, AP HURLEY, BF AF TREUTH, MS RYAN, AS PRATLEY, RE RUBIN, MA MILLER, JP NICKLAS, BJ SORKIN, J HARMAN, SM GOLDBERG, AP HURLEY, BF TI EFFECTS OF STRENGTH TRAINING ON TOTAL AND REGIONAL BODY-COMPOSITION IN OLDER MEN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE AGING; RESISTANCE TRAINING; WEIGHT TRAINING ID HEAVY-RESISTANCE EXERCISE; X-RAY ABSORPTIOMETRY; ELDERLY SUBJECTS; SKELETAL-MUSCLE; TOMOGRAPHY; INTENSITY; DISEASE; INVIVO; TISSUE; FAT AB The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and hydrodensitometry in 13 untrained healthy men [60 +/- 4 (SD) yr]. Nine additional men (62 +/- 6 yr) served as inactive controls. The strength-training program resulted in substantial increases in both upper (39 +/- 8%; P < 0.001) and lower (42 +/- 14%; P < 0.001) body strength. Total fat-free mass (FFM) increased by 2 kg (62.0 +/- 7.1 to 64.0 +/- 7.2 kg; P < 0.001), and total fat mass decreased by the same amount (23.8 +/- 6.7 to 21.8 +/- 6.0 kg; P < 0.001) when measured by DEXA. When measured by hydrodensitometry, similar increases in FFM (61.3 +/- 7.8 to 63.0 +/- 7.6 kg, P < 0.01) and decreases in fat mass (23.8 +/- 7.9 to 22.1 +/- 7.7 kg; P < 0.001) were observed. When measured by DEXA, FFM was increased in the arms (6.045 +/- 0.860 to 6.418 +/- 0.803 kg; P < 0.01), legs (19.416 +/- 2.228 to 20.131 +/- 2.303 kg; P < 0.001), and trunk (29.229 +/- 4.108 to 30.134 +/- 4.184 kg; P < 0.01), whereas fat mass was reduced in the arms (2.383 +/- 0.830 to 2.128 +/- 0.714 kg; P < 0.01), legs (7.583 +/- 1.675 to 6.945 +/- 1.551 kg; P < 0.001), and trunk (12.216 +/- 4.143 to 11.281 +/- 3.653 kg; P < 0.01) as a result of training. MRI analysis revealed significant increases in midthigh muscle cross-sectional area (161 +/- 19 to 172 +/- 18 cm(2); P < 0.01) and significant reductions in midthigh subcutaneous fat (65 +/- 19 to 59 +/- 17 cm(2); P < 0.05). These changes in body composition were not associated with changes in serum concentration of growth hormone, insulin-like growth factor I, or testosterone. None of the measured variables changed significantly in the control subjects. Thus, strength training increases regional and total lean mass and decreases regional and total fat mass in middle-aged and older men. The mechanisms for these changes will require further study. C1 UNIV MARYLAND,DEPT KINESIOL,COLLEGE PK,MD 20742. UNIV MARYLAND,DEPT HUMAN NUTR & FOOD SYST,COLLEGE PK,MD 20742. UNIV MARYLAND,SCH MED,DIV GERONTOL,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,ENDOCRINOL METAB SECT,BALTIMORE,MD 21224. FU NIA NIH HHS [R01-AG-07660, KO8-AG-00494, P01-AG-04402] NR 37 TC 161 Z9 166 U1 4 U2 13 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 AUG PY 1994 VL 77 IS 2 BP 614 EP 620 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PB787 UT WOS:A1994PB78700017 PM 8002507 ER PT J AU GORDON, CT KRASNEWICH, D WHITE, B LENANE, M RAPOPORT, JL AF GORDON, CT KRASNEWICH, D WHITE, B LENANE, M RAPOPORT, JL TI TRANSLOCATION INVOLVING CHROMOSOME-1 AND CHROMOSOME-7 IN A BOY WITH CHILDHOOD-ONSET SCHIZOPHRENIA SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Note ID LINKAGE ANALYSIS; PHENOMENOLOGY; FAMILIES; CHILDREN; MARKERS; DISEASE; DEFECT; AUTISM; RISK C1 NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,HUMAN GENET BRANCH,BETHESDA,MD 20892. NIDDKD,CHEM BIOL LAB,CYTOGENET UNIT,BETHESDA,MD 20892. NR 34 TC 32 Z9 34 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD AUG PY 1994 VL 24 IS 4 BP 537 EP 545 DI 10.1007/BF02172134 PG 9 WC Psychology, Developmental SC Psychology GA NX830 UT WOS:A1994NX83000010 PM 7961336 ER PT J AU MARCONI, RT SAMUELS, DS LANDRY, RK GARON, CF AF MARCONI, RT SAMUELS, DS LANDRY, RK GARON, CF TI ANALYSIS OF THE DISTRIBUTION AND MOLECULAR HETEROGENEITY OF THE OSPD GENE AMONG THE LYME-DISEASE SPIROCHETES - EVIDENCE FOR LATERAL GENE EXCHANGE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACTERIUM BORRELIA-BURGDORFERI; SIGNATURE NUCLEOTIDE ANALYSIS; SP-NOV; MONOCLONAL-ANTIBODIES; LINEAR CHROMOSOME; MEMBRANE-PROTEINS; ESCHERICHIA-COLI; EXPRESSING OSPA; PLASMID; AGENT AB Analysis of the ospD gene has revealed that this gene is not universal among Lyme disease spirochete isolates. The gene was found to be carried by 90, 50, and 24% of the Borrelia garinii, B. afzelii, and B. burgdorferi isolates tested. Size variability in the ospD-encoding plasmid was also observed. Sequence analysis has demonstrated the presence of various numbers of a 17-bp repeated sequence in the upstream control (promoter) region of the gene. In addition, a region within the coding sequence where various insertions, deletions, and direct repeats occur was identified. ospD gene sequences from 31 different isolates were determined and utilized in pairwise sequence comparisons and construction of a gene tree. These analyses suggest that the ospD gene was the target of several recombinational events and that the gene was recently acquired by Lyme disease spirochetes and laterally transferred between species. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 48 TC 74 Z9 74 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 AUG PY 1994 VL 176 IS 15 BP 4572 EP 4582 PG 11 WC Microbiology SC Microbiology GA NY398 UT WOS:A1994NY39800014 PM 7913928 ER PT J AU JOHNSON, VG NICHOLLS, PJ AF JOHNSON, VG NICHOLLS, PJ TI IDENTIFICATION OF A SINGLE AMINO-ACID SUBSTITUTION IN THE DIPHTHERIA-TOXIN A CHAIN OF CRM-228 RESPONSIBLE FOR THE LOSS OF ENZYMATIC-ACTIVITY SO JOURNAL OF BACTERIOLOGY LA English DT Note ID NAD BINDING-SITE; CORYNEBACTERIOPHAGE-BETA; NUCLEOTIDE-SEQUENCE; ASPARTIC-ACID; FRAGMENT-A; TRANSLOCATION; MUTATIONS; MUTANTS; DOMAIN; GENE AB CRM 228 (T. Uchida, A. M. Pappenheimer, and R. Greany, J. Biol. Chem. 248:3838-3844, 1973), a mutant form of diphtheria toxin which completely lacks ADP-ribosyltransferase activity, contains five amino acid substitutions. The two amino acid changes that fall within the A chain of the toxin (G79D and E162K) were separately analyzed by substituting a variety of other amino acids at these sites. The substitution at position 79 (G79D) singularly appears to account for the loss of enzymatic activity found in CRM 228. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP JOHNSON, VG (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BLDG 29,RM 103,BETHESDA,MD 20892, USA. NR 34 TC 6 Z9 6 U1 0 U2 0 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 AUG PY 1994 VL 176 IS 15 BP 4766 EP 4769 PG 4 WC Microbiology SC Microbiology GA NY398 UT WOS:A1994NY39800039 PM 8045910 ER PT J AU WOODGATE, R SINGH, M KULAEVA, OI FRANK, EG LEVINE, AS KOCH, WH AF WOODGATE, R SINGH, M KULAEVA, OI FRANK, EG LEVINE, AS KOCH, WH TI ISOLATION AND CHARACTERIZATION OF NOVEL PLASMID-ENCODED UMUC MUTANTS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA POLYMERASE-III; SINGLE-STRANDED VECTOR; ESCHERICHIA-COLI; RECA PROTEIN; UV MUTAGENESIS; ULTRAVIOLET-LIGHT; SOS MUTAGENESIS; CHEMICAL MUTAGENESIS; CYCLOBUTANE DIMER; GROE MUTANTS AB Most inducible mutagenesis in Escherichia coli is dependent upon the activity of the UmuDC proteins. The role of UmuC in this process is poorly understood, possibly because of the limited number of genetically characterized umuC mutants. To better understand the function of the UmuC protein in mutagenic DNA repair, we have isolated several novel plasmid-encoded umuC mutants. A multicopy plasmid that expressed UmuC at physiological levels was constructed and randomly mutagenized in vitro by exposure to hydroxylamine. Mutated plasmids were introduced into the umu tester strain RW126, and 16 plasmids that were unable to promote umuC-dependent spontaneous mutator activity were identified by a colorimetric papillation assay. Interestingly, these plasmid mutants fell into two classes: (i) 5 were expression mutants that produced either too little or too much wild-type UmuC protein, and (ii) 11 were plasmids with structural changes in the UmuC protein. Although hydroxylamine mutagenesis was random, most of the structural mutants identified in the screen were localized to two regions of the UmuC protein; four mutations were found in a stretch of 30 amino acids (residues 133 to 162) in the middle of the protein, while four other mutations (three of which resulted in a truncated UmuC protein) were localized in the last 50 carboxyl-terminal amino acid residues. These new plasmid umuC mutants, together with the previously identified chromosomal umuC25, umuC36, and umuC104 mutations that we have also cloned, should prove extremely useful in dissecting the genetic and biochemical activities of UmuC in mutagenic DNA repair. C1 US FDA,MOLEC BIOL BRANCH,WASHINGTON,DC 20204. RP WOODGATE, R (reprint author), NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS,BLDG 6,ROOM 1A13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 58 TC 34 Z9 35 U1 1 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 AUG PY 1994 VL 176 IS 16 BP 5011 EP 5021 PG 11 WC Microbiology SC Microbiology GA PA426 UT WOS:A1994PA42600029 PM 8051014 ER PT J AU SHLYAKHTENKO, LS APPELLA, E HARRINGTON, RE KUTYAVIN, I LYUBCHENKO, YL AF SHLYAKHTENKO, LS APPELLA, E HARRINGTON, RE KUTYAVIN, I LYUBCHENKO, YL TI STRUCTURE OF 3-WAY DNA JUNCTIONS .2. EFFECTS OF EXTRA BASES AND MISMATCHES SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID CRO PROTEIN; 3-ARM; COMPLEX AB The structure of three-way DNA junctions, containing two linear double helices (arms) and a hairpin as a third arm, was studied by means of a cyclization technique. In addition to branched molecules containing perfect base-paring in helical parts, three-way junctions with mismatches and extra non-complementary nucleotides (bulges) at junction points were studied. Molecules thus designed were ligated at identical conditions and their geometry was compared through the analysis of the efficiency of circle formation. The analysis showed that irregularities in base pairing listed above dramatically change the static and dynamic structural characteristics of the three-way junctions. All mismatches facilitate the kink between linear arms, but quantitatively, the effect depends on the position of the mismatch. The effect is maximal for GG-mismatch placed at the hairpin junction point. The results for bulges are of different kind, and they lead us to conclude that the three-way DNA junction with unpaired nucleotides adopts a T-like geometry with an angle around 90 degrees between arms containing the bulge and two other arms coaxially stacked. Broad distribution of circles indicates that this T-form geometry of bulge-containing junction is more flexible than initial pyramidal structure predominantly due to high mobility of the third arm. C1 ARIZONA STATE UNIV,DEPT MICROBIOL,TEMPE,AZ 85287. ARIZONA STATE UNIV,DEPT PHYS,TEMPE,AZ 85287. UNIV NEVADA,DEPT BIOCHEM,RENO,NV 89557. NCI,CELL BIOL LAB,BETHESDA,MD 20892. MICROPROBE CORP,BOTHELL,WA 98021. NR 19 TC 17 Z9 17 U1 0 U2 5 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD AUG PY 1994 VL 12 IS 1 BP 131 EP 143 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PJ683 UT WOS:A1994PJ68300008 PM 7848563 ER PT J AU LUSTIG, B COVELL, DG JERNIGAN, RL AF LUSTIG, B COVELL, DG JERNIGAN, RL TI CONFORMATIONS OF TRANSFER-RNA - BASE-PAIRING AND STACKING SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID PHENYLALANINE TRANSFER-RNA; 3-DIMENSIONAL STRUCTURE; RESTRAINED REFINEMENT; STRUCTURE PREDICTION; MODEL AB The Phe t-RNA structure can be fit with one point per nucleotide to lattice models, and a fit for the 76 points to a face-centered cubic lattice is achieved with an RMS of 1.76 A There are 32 chain folds possible upon these points. Because it is impossible to calculate directly all combinations of potential base pairs for these cases, an alternative is to determine low energy secondary structures and subsequently the tertiary pairs. For each lattice fold, the low energy secondary structures are generated from a list of proximal bases. From the lists of remaining possible tertiary pairs, all combinations are generated, and these include 2,365,440 allowed conformers. Among the possible types of non-native conformational variations observed is slip pairing, accompanied by a bulge, at the end of a stem. Small changes in secondary structure can result in different tertiary pairs. Other calculations, not constrained to the t-RNA shape, are presented that involve the packing of rigid stems on a flexible internal loop. For a simple cubic lattice there are 36,484,128 lattice folds for the sixteen bases enclosing the internal loop. By attaching rigid stems and accounting for their excluded volume these are reduced to only 258,979 possible configurations. The most common stacking arrangements involve the usual two pairs of stacked stems indicated in the crystal structure. The present enumerations suggest that a completely thorough exploration of three dimensional RNA structures is feasible only with prior specification of restrictions on conformational freedom, such as those given by secondary structures. C1 PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21701. RP LUSTIG, B (reprint author), NCI,WASHINGTON SCI CTR,MATH BIOL LAB,6010 EXECUT BLVD,RM 217,BETHESDA,MD 20892, USA. RI Jernigan, Robert/A-5421-2012 NR 19 TC 6 Z9 6 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD AUG PY 1994 VL 12 IS 1 BP 145 EP 161 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PJ683 UT WOS:A1994PJ68300009 PM 7848564 ER PT J AU DIMITROV, S DASSO, MC WOLFFE, AP AF DIMITROV, S DASSO, MC WOLFFE, AP TI REMODELING SPERM CHROMATIN IN XENOPUS-LAEVIS EGG EXTRACTS - THE ROLE OF CORE HISTONE PHOSPHORYLATION AND LINKER HISTONE B4 IN CHROMATIN ASSEMBLY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DNA-REPLICATION; RNA GENES; TRANSCRIPTION INVITRO; NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; CELL-NUCLEI; NUCLEOSOME; PROTEIN; OOCYTES; NUCLEOPLASMIN AB We find that the remodeling of the condensed Xenopus laevis sperm nucleus into the paternal pronucleus in egg extracts is associated with phosphorylation of the core histones H2A, H2A.X and H4, and uptake of a linker histone B4 and a HMG 2 protein. Histone B4 is required for the assembly of chromatosome structures in the pronucleus. However neither B4 nor core histone phosphorylation are required for the assembly of spaced nucleosomal arrays. We suggest that the spacing of nucleosomal arrays is determined by interaction between adjacent histone octamers under physiological assembly conditions. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI dimitrov, stefan/M-7697-2013; OI Dasso, Mary/0000-0002-5410-1371 NR 89 TC 113 Z9 113 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1994 VL 126 IS 3 BP 591 EP 601 DI 10.1083/jcb.126.3.591 PG 11 WC Cell Biology SC Cell Biology GA NZ252 UT WOS:A1994NZ25200001 PM 8045925 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI THE ROLE OF TRANSCRIPTION FACTORS, CHROMATIN STRUCTURE AND DNA-REPLICATION IN 5-S RNA GENE-REGULATION SO JOURNAL OF CELL SCIENCE LA English DT Note DE TRANSCRIPTION; CHROMATIN; REPLICATION; RNA POLYMERASE III; RIBOSOMAL RNA GENE ID CLASS-III GENES; XENOPUS-LAEVIS; DEVELOPMENTAL REGULATION; HISTONE ACETYLATION; POLYMERASE-III; MESSENGER-RNA; FACTOR TFIIIA; 5S-RNA GENES; INVITRO; COMPLEX AB Differential expression of the oocyte and somatic 5 S RNA genes during Xenopus development can be explained by changes in transcription factor and histone interactions with the two types of gene. Both factors and histones bind 5 S RNA genes with specificity. Protein-protein interactions determine the stability bf potentially transcriptionally active or repressed nucleoprotein complexes. A decline in transcription factor abundance, differential binding of transcription factors to oocyte and somatic 5 S genes, and increased competition with the histones for association with DNA during early embryogenesis, can account for the developmental decision to selectively repress the oocyte genes, while retaining the somatic genes in the transcriptionally active state. The 5 S ribosomal genes of Xenopus are perhaps the simplest eukaryotic genes to show regulated expression during development. A large multigene family (oocyte 5 S DNA) is transcriptionally active in oocytes but is repressed in somatic cells, whereas a small multigene family (somatic 5 S DNA) is active in both cell types. A potential molecular mechanism to explain the developmental switch that turns off oocyte 5 S DNA transcription has been experimentally reconstructed in vitro and more recently tested in vivo. Central to this mechanism is the specific association of both transcription factors and histones with 5 S RNA genes. How the interplay of histones and transcription factors is thought to affect transcription, and how their respective contributions might change during development from an oocyte, to an embryo and eventually to a somatic cell is the focus of this review. RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 87 TC 43 Z9 44 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 AUG PY 1994 VL 107 BP 2055 EP 2063 PN 8 PG 9 WC Cell Biology SC Cell Biology GA PD475 UT WOS:A1994PD47500001 PM 7983167 ER PT J AU SAROFF, HA AF SAROFF, HA TI GLYCINE - A SIMPLE ZWITTERION - ANALYSIS OF ITS PROTON-BINDING ISOTHERM SO JOURNAL OF CHEMICAL EDUCATION LA English DT Article ID IONIZATION RP SAROFF, HA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 227,BETHESDA,MD 20892, USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-9584 J9 J CHEM EDUC JI J. Chem. Educ. PD AUG PY 1994 VL 71 IS 8 BP 637 EP 643 PG 7 WC Chemistry, Multidisciplinary; Education, Scientific Disciplines SC Chemistry; Education & Educational Research GA PC788 UT WOS:A1994PC78800011 ER PT J AU PERICO, A PRATOLONGO, R FREED, KF SZABO, A AF PERICO, A PRATOLONGO, R FREED, KF SZABO, A TI TORSIONAL TIME-CORRELATION FUNCTION FOR ONE-DIMENSIONAL SYSTEMS WITH BARRIER CROSSING - PERIODIC POTENTIAL SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DYNAMICS AB The one-variable Smoluchowski equation is used to study various systematic approximation schemes to the torsional angle time correlation function for a system with a multibarrier periodic potential. The memory function is evaluated as a function of the barrier height using both the Mori continued fraction expansion and a related but more efficient matrix expansion method. An exact integral relation for the correlation time is derived and is compared with the approximations. C1 UNIV CHICAGO,JAMES FRANCK INST,CHICAGO,IL 60637. UNIV CHICAGO,DEPT CHEM,CHICAGO,IL 60637. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. RP PERICO, A (reprint author), CNR,IST STUDI CHIMICOFIS MACROMOLEC SINTET & NAT,GENOA,ITALY. RI Szabo, Attila/H-3867-2012 NR 12 TC 10 Z9 10 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD AUG 1 PY 1994 VL 101 IS 3 BP 2554 EP 2561 DI 10.1063/1.467628 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA NY002 UT WOS:A1994NY00200084 ER PT J AU PETRIDES, JS MUELLER, GP KALOGERAS, KT CHROUSOS, GP GOLD, PW DEUSTER, PA AF PETRIDES, JS MUELLER, GP KALOGERAS, KT CHROUSOS, GP GOLD, PW DEUSTER, PA TI EXERCISE-INDUCED ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS - MARKED DIFFERENCES IN THE SENSITIVITY TO GLUCOCORTICOID SUPPRESSION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; DEXAMETHASONE SUPPRESSION; ADRENOCORTICOTROPIC HORMONE; ARGININE VASOPRESSIN; CORTISOL SECRETION; TREADMILL EXERCISE; ACTH-SECRETION; RESPONSES; CRF; RAT AB Treadmill exercise activates the hypothalamic-pituitary-adrenal axis and evokes metabolic responses proportional to exercise intensity and duration. To determine whether glucocorticoid administration would alter humoral and metabolic regulation during exercise, we administered 4 mg dexamethasone (DEX) or placebo to 11 normal, moderately trained men (19-42 yr old) in a double blinded random fashion 4 h before high intensity intermittent treadmill running. Plasma levels of ACTH, cortisol, arginine vasopressin (AVP), lactate, and glucose were measured before, during, and after exercise. A wide range of ACTH responses were seen in the DEX-treated group and arbitrarily defined as two subsets of individuals according to their responses to dexamethasone: DEX nonsuppressors and DEX suppressors. Exercise-induced increases in heart rate and circulating concentrations of cortisol, AVP, lactate, and glucose were all significantly greater (P < 0.05) in nonsuppressors (n = 4) compared to suppressors (n = 7) after both placebo and DEX administration. Interestingly, heart rate, AVP, and lactate responses were unaltered by DEX alone in both groups. In summary, this study demonstrates that normal individuals exhibit differential neuroendocrine and metabolic responses to exercise and pituitary/adrenal suppression after pretreatment with DEX. These findings reflect marked individual differences in the stress response to exercise that may derive from or lead to differential glucocorticoid negative feedback sensitivity in humans. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20814 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 36 TC 65 Z9 65 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1994 VL 79 IS 2 BP 377 EP 383 DI 10.1210/jc.79.2.377 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB505 UT WOS:A1994PB50500010 PM 8045951 ER PT J AU MARIN, G DOMENE, HM BARNES, KM BLACKWELL, BJ CASSORLA, FG CUTLER, GB AF MARIN, G DOMENE, HM BARNES, KM BLACKWELL, BJ CASSORLA, FG CUTLER, GB TI THE EFFECTS OF ESTROGEN PRIMING AND PUBERTY ON THE GROWTH-HORMONE RESPONSE TO STANDARDIZED TREADMILL EXERCISE AND ARGININE-INSULIN IN NORMAL GIRLS AND BOYS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SHORT CHILDREN; STIMULATION; SECRETION; TESTS; DEFICIENCY; CLONIDINE; GH AB To determine the effects of puberty and estrogen priming on the GH response to standardized treadmill exercise and arginine-insulin in normal boys and girls, we performed tests in 84 normal children (41 girls and 43 boys) representing all stages of puberty. A subset of the prepubertal children received the tests twice, with or without the administration of ethinyl estradiol (40 mu g/m(2) daily) for 2 days before the tests. The peak GH response to the three tests increased significantly with pubertal stage (r = 0.57; P < 0.0001), but did not differ between boys and girls at the same stage. With advancing puberty, the percentage of normal children who failed to attain a GH level greater than 7 mu g/L during any of the three tests declined from 61% at pubertal stage 1 to 44% at stage 2, 11% at stage 3, and 0% at stages 4 and 5. Administration of estrogen to the prepubertal subjects raised the normal range for the peak GH response to the three tests from 1.9-20.3 to 7.2-40.5 mu g/L. We conclude that both puberty and estrogen administration significantly increase the peak GH response to exercise, arginine, or insulin in normal subjects. Moreover, the conventional criterion that the peak GH response to three stimulation tests should exceed 7 mu g/L was applicable in our study only to subjects who had attained pubertal stage 4 or 5 or who had received estrogen administration. RP MARIN, G (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N 262, BETHESDA, MD 20892 USA. NR 25 TC 182 Z9 185 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 AUG PY 1994 VL 79 IS 2 BP 537 EP 541 DI 10.1210/jc.79.2.537 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB505 UT WOS:A1994PB50500037 PM 8045974 ER PT J AU KRAIEM, Z SADEH, O BLITHE, DL NISULA, BC AF KRAIEM, Z SADEH, O BLITHE, DL NISULA, BC TI HUMAN CHORIONIC-GONADOTROPIN STIMULATES THYROID-HORMONE SECRETION, IODIDE UPTAKE, ORGANIFICATION, AND ADENOSINE-3',5'-MONOPHOSPHATE FORMATION IN CULTURED HUMAN THYROCYTES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GESTATIONAL TROPHOBLASTIC NEOPLASIA; HUMAN TSH RECEPTORS; SERUM-FREE MEDIUM; CARBOHYDRATE-COMPOSITION; THYROTROPIC ACTIVITY; SUSPENSION-CULTURE; POLARITY REVERSAL; COLLAGEN GEL; CELLS; PREGNANCY AB Despite extensive studies, the issue of whether hCG possesses intrinsic thyrotropic activity remains unresolved. This is mainly because in the experimental systems used so far, the parameters measured did not include the thyroid-specific functions of iodine organification and the hormonal end-point response, T-3 secretion, and cells of nonhuman origin were employed, constituting a major drawback in view of the wide variation in sensitivity of thyroid responsiveness to hCG in different species. We investigated the thyrotropic activity of hCG, using for this purpose a novel homologous assay system consisting of human thyroid follicles cultured suspended in collagen gel in serum-ree medium. Under these conditions, the cells are organized as follicular three-dimensional structures with normal polarity, enabling enhanced responsiveness to hormonal stimulation. The parameters measured were the thyroid-specific functions of iodide uptake, organification, and T-3 secretion, as well as formation of the second messenger, cAMP. Purified hCG (biological potency, 21,700 IU/mg; with no detectable TSH by immunoradiometric TSH assay) did indeed exhibit thyroid stimulatory activity. At doses ranging from 10-400 mg/L, hCG induced a dose-dependent increase in the parameters measured. The rise from basal to maximal levels achieved after hCG stimulation was 1.3 to 3.6 pmol/well for cAMP formation, 34 to 21,408 cpm/well for iodide uptake, 261 to 20,167 cpm/well for iodide organification, and 40 to 927 fmol/well for T-3 secretion. Maximal levels elicited by hCG (200 mg/L) relative to maximal values achieved with bovine TSH were 49%, 56%, and 42% for iodide uptake, organification, and T-3 secretion, respectively, and only 5% for cAMP. Iodide uptake proved to be the most sensitive indicator of the thyrotropic activity of hCG, with increases occurring at a concentration of 10 mg/L. Acting as a partial agonist, hCG was also capable of dose-dependently inhibiting TSH-timulated cAMP formation. The free alpha- and beta- subunits of hCG, at doses as high as 200 mg/L, had no thyroid-stimulating effect. The present data thus clearly demonstrate that hCG is a human thyroid stimulator. Moreover, hCG managed to elicit substantial biological cell responses in human thyrocytes while evoking minimal amounts of cAMP, illustrating the concept of cAMP superfluity and highlighting the potential pitfalls of using cAMP as a reliable measure of hormonal bioactivity. C1 TEL AVIV UNIV, FAC MED, TEL AVIV, ISRAEL. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP KRAIEM, Z (reprint author), CARMEL HOSP, ENDOCRINE RES UNIT, 7 MICHAL ST, IL-34362 HAIFA, ISRAEL. NR 37 TC 31 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 AUG PY 1994 VL 79 IS 2 BP 595 EP 599 DI 10.1210/jc.79.2.595 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB505 UT WOS:A1994PB50500047 PM 8045981 ER PT J AU SHARARA, FI NIEMAN, LK AF SHARARA, FI NIEMAN, LK TI IDENTIFICATION AND CELLULAR-LOCALIZATION OF GROWTH-HORMONE RECEPTOR GENE-EXPRESSION IN THE HUMAN OVARY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID I IGF-I; GRANULOSA-CELLS; INDUCED DIFFERENTIATION; DEFICIENCY; INVITRO AB While in vivo and in vitro studies in rodents, pigs and women suggest that growth hormone (GH) can stimulate ovarian steroidogenesis, it is not known if this effect is mediated by a direct action on the ovary. The absence of GH receptor (GHR) messenger RNA would mitigate against a direct ovarian effect. We used the reverse transcriptase-polymerase chain reaction and in situ hybridization to examine whether the GHR mRNA was present in homogenates of seven human ovaries or in tissue sections of ten ovaries. GHR gene expression was detected in PCR products after Southern blot hybridization using an oligoprobe directed to the intracellular domain sharing no homology to the prolactin receptor. In situ hybridization using the same digoxigenin-labeled oligoprobe localized the GHR mRNA in the granulosa cells of dominant and antral follicles, corpus luteum, corpora albicans and the endothelium of blood vessels. GHR mRNA was not detected in preantral follicles, theca interna, theca externa, oocytes, or stroma. The presence of GHR mRNA in human granulosa cells and corpus luteum, taken together with previous studies showing GH-induced stimulation of estradiol and progesterone secretion, suggest that GH may play a direct role in the development of the human follicle. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 17 TC 61 Z9 61 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1994 VL 79 IS 2 BP 670 EP 672 DI 10.1210/jc.79.2.670 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB505 UT WOS:A1994PB50500061 PM 7519196 ER PT J AU WAHL, SM ALLEN, JB HINES, KL IMAMICHI, T WAHL, AM FURCHT, LT MCCARTHY, JB AF WAHL, SM ALLEN, JB HINES, KL IMAMICHI, T WAHL, AM FURCHT, LT MCCARTHY, JB TI SYNTHETIC FIBRONECTIN PEPTIDES SUPPRESS ARTHRITIS IN RATS BY INTERRUPTING LEUKOCYTE ADHESION AND RECRUITMENT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INFLAMMATION; SYNOVIUM; INTEGRINS; MATRIX; PROTEOGLYCANS ID HEPARIN-BINDING DOMAIN; MELANOMA CELL-ADHESION; FN-C/H-II; SULFATE PROTEOGLYCAN; LYMPHOID-CELLS; T-CELLS; INTEGRIN; EXPRESSION; INFLAMMATION; RECOGNITION AB In an experimental model of arthritis, increased leukocyte adhesion is associated with the evolution of acute and chronic synovial inflammation. Whereas peripheral blood mononuclear cells (PBMC) from control animals bind minimally to fibronectin matrices, PBMC from animals receiving arthropathic doses of bacterial cell walls demonstrate increased integrin mRNA expression and enhanced adhesion. To determine whether this augmented adhesion was causal in the development of synovial pathology, peptides synthesized from several fibronectin domains which inhibited leukocyte adhesion in vitro were administered to arthritic animals either as free peptides or coupled to a carrier molecule. Not only were peptides containing either the RGD or CS-1 cell-binding domains inhibitory to chronic synovial pathology (articular index = 10.5 +/- 0.3 for untreated animals compared to 1.25 +/- 0.25 for RGD and 2.5 +/- 0.7 for CS-1), but three peptides synthesized from the carboxy-terminal 33- kD heparin-binding domain of fibronectin were also found to significantly inhibit leukocyte recruitment and the evolution of arthritis. Based on these data, which are the first to explore the therapeutic potential of heparin-binding fibronectin peptides in chronic inflammation, it appears that antagonism of cellular adhesion and recruitment by fibronectin peptides may provide an important mechanism for modulating the multi-step adhesion process and attenuating aberrant inflammatory responses. C1 UNIV MINNESOTA,CTR BIOMED ENGN,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. RP WAHL, SM (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,RM 331,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA21463, CA43924] NR 49 TC 111 Z9 112 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1994 VL 94 IS 2 BP 655 EP 662 DI 10.1172/JCI117382 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PA250 UT WOS:A1994PA25000028 PM 8040319 ER PT J AU DABHOLKAR, M VIONNET, J BOSTICKBRUTON, F YU, JJ REED, E AF DABHOLKAR, M VIONNET, J BOSTICKBRUTON, F YU, JJ REED, E TI MESSENGER-RNA LEVELS OF XPAC AND ERCC1 IN OVARIAN-CANCER TISSUE CORRELATE WITH RESPONSE TO PLATINUM-BASED CHEMOTHERAPY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE XPAC; ERCC1; OVARIAN CANCER; PLATINUM COMPOUNDS ID DNA EXCISION REPAIR; A XERODERMA-PIGMENTOSUM; HOST-CELL REACTIVATION; HIGH-DOSE CARBOPLATIN; CISPLATIN SENSITIVITY; GENE; EXPRESSION; PROTEINS; COMPLEMENTATION; IDENTIFICATION AB Nucleotide excision repair is a DNA repair pathway that is highly conserved in nature, with analogous repair systems described in Escherichia coli, yeast, and mammalian cells. The rate-limiting step, DNA damage recognition and excision, is effected by the protein products of the genes ERCC1 and XPAC. We therefore assessed mRNA levels of ERCC1 and XPAC in malignant ovarian cancer tissues from 28 patients that were harvested before the administration of platinum-based chemotherapy. Cancer tissues from patients whose tumors were clinically resistant to therapy (n = 13) showed greater levels of total ERCC1 mRNA (P = 0.059), full length transcript of ERCC1 mRNA (P = 0.026), and XPAC mRNA (P = 0.011), as compared with tumor tissues from those individuals clinically sensitive to therapy (n = 15). In 19 of these tissues, the percentage of alternative splicing of ERCC1 mRNA was assessed. ERCC1 splicing was highly variable, with no difference observed between responders and nonresponders. The alternatively spliced species constituted 2-58% of the total ERCC1 mRNA in responders (median = 18%) and 4-71% in nonresponders (median = 13%). These data suggest greater activity of the DNA excision repair genes ERCC1 and XPAC in ovarian cancer tissues of patients clinically resistant to platinum compounds. These data also indicate highly variable splicing of ERCC1 mRNA in ovarian cancer tissues in vivo, whether or not such tissues are sensitive to platinum-based therapy. C1 NCI, MED BRANCH, CLIN PHARMACOL BRANCH, MED OVARIAN CANC SECT, BETHESDA, MD 20892 USA. NR 35 TC 341 Z9 350 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1994 VL 94 IS 2 BP 703 EP 708 DI 10.1172/JCI117388 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PA250 UT WOS:A1994PA25000034 PM 8040325 ER PT J AU YANG, JC TOPALIAN, SL PARKINSON, D SCHWARTZENTRUBER, DJ WEBER, JS ETTINGHAUSEN, SE WHITE, DE STEINBERG, SM COLE, DJ KIM, HI LEVIN, R GULERIA, A MACFARLANE, MP WHITE, RL EINHORN, JH SEIPP, CA ROSENBERG, SA AF YANG, JC TOPALIAN, SL PARKINSON, D SCHWARTZENTRUBER, DJ WEBER, JS ETTINGHAUSEN, SE WHITE, DE STEINBERG, SM COLE, DJ KIM, HI LEVIN, R GULERIA, A MACFARLANE, MP WHITE, RL EINHORN, JH SEIPP, CA ROSENBERG, SA TI RANDOMIZED COMPARISON OF HIGH-DOSE AND LOW-DOSE INTRAVENOUS INTERLEUKIN-2 FOR THE THERAPY OF METASTATIC RENAL-CELL CARCINOMA - AN INTERIM-REPORT SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; SUBCUTANEOUS INTERLEUKIN-2; PHASE-II; IMMUNOTHERAPY; TOXICITY; TRIAL C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP YANG, JC (reprint author), NCI,SURG BRANCH,BLDG 10,9000 ROCKVILLE PIKE,ROOM 2B42,BETHESDA,MD 20892, USA. NR 20 TC 140 Z9 143 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1994 VL 12 IS 8 BP 1572 EP 1576 PG 5 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700008 PM 8040669 ER PT J AU WILSON, WH BERG, SL BRYANT, G WITTES, RE BATES, S FOJO, A STEINBERG, SM GOLDSPIEL, BR HERDT, J OSHAUGHNESSY, J BALIS, FM CHABNER, BA AF WILSON, WH BERG, SL BRYANT, G WITTES, RE BATES, S FOJO, A STEINBERG, SM GOLDSPIEL, BR HERDT, J OSHAUGHNESSY, J BALIS, FM CHABNER, BA TI PACLITAXEL IN DOXORUBICIN-REFRACTORY OR MITOXANTRONE-REFRACTORY BREAST-CANCER - A PHASE I/II TRIAL OF 96-HOUR INFUSION SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; EVERY 21 DAYS; I TRIAL; CELL-LINES; TAXOL; PHARMACOKINETICS; EXPRESSION RP WILSON, WH (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 31,ROOM 3A44,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 26 TC 227 Z9 231 U1 1 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 AUG PY 1994 VL 12 IS 8 BP 1621 EP 1629 PG 9 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700015 PM 7913721 ER PT J AU FRELICK, RW AF FRELICK, RW TI THE COMMUNITY CLINICAL ONCOLOGY PROGRAM (CCOP) STORY - REVIEW OF COMMUNITY ONCOLOGISTS EXPERIENCES WITH CLINICAL RESEARCH TRIALS IN CANCER WITH AN EMPHASIS ON THE CCOP OF THE NATIONAL-CANCER-INSTITUTE BETWEEN 1982 AND 1987 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PARTICIPATION; HOSPITALS; PATTERNS; QUALITY; THERAPY C1 NCI,COMMUNITY CLIN ONCOL PROGRAMS,BETHESDA,MD. DELAWARE DIV PUBL HLTH,DELAWARE COMMUNITY CLIN ONCOL PROGRAM,MED CTR,WILMINGTON,DE. NR 32 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1994 VL 12 IS 8 BP 1718 EP 1723 PG 6 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700026 PM 8040683 ER PT J AU SEIDMAN, AD BARRETT, S CANEZO, S AF SEIDMAN, AD BARRETT, S CANEZO, S TI PHOTOPSIA DURING 3-HOUR PACLITAXEL ADMINISTRATION AT DOSES GREATER-THAN-OR-EQUAL-TO-250 MG/M(2) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 NCI,BETHESDA,MD. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,NEW YORK,NY, USA. NR 4 TC 22 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1994 VL 12 IS 8 BP 1741 EP 1742 PG 2 WC Oncology SC Oncology GA PA257 UT WOS:A1994PA25700035 PM 7913722 ER PT J AU RUDORFER, MV YONKERS, KA HARRISON, W AF RUDORFER, MV YONKERS, KA HARRISON, W TI THE INCLUSION OF WOMEN IN PSYCHOPHARMACOLOGICAL TRIALS (VOL 13, PG 380, 1993) SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Correction, Addition ID GENDER DIFFERENCES; PHARMACOKINETICS; PHARMACODYNAMICS RP RUDORFER, MV (reprint author), NIMH,CLIN TREATMENT RES BRANCH,ROCKVILLE,MD, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1994 VL 14 IS 4 BP 288 EP 288 DI 10.1097/00004714-199408000-00018 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NX836 UT WOS:A1994NX83600018 PM 7962693 ER PT J AU SCHMIEDEKAMP, AM TOPOL, IA BURT, SK RAZAFINJANAHARY, H CHERMETTE, H PFALTZGRAFF, T MICHEJDA, CJ AF SCHMIEDEKAMP, AM TOPOL, IA BURT, SK RAZAFINJANAHARY, H CHERMETTE, H PFALTZGRAFF, T MICHEJDA, CJ TI TRIAZENE PROTON AFFINITIES - A COMPARISON BETWEEN DENSITY-FUNCTIONAL, HARTREE-FOCK, AND POST-HARTREE-FOCK METHODS SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID CONFORMATIONAL-ANALYSIS; ENERGIES; 1,3-DIALKYL-3-ACYLTRIAZENES; DECOMPOSITION; OPTIMIZATION; ENERGETICS; GEOMETRIES; ABINITIO; AGENTS; ACID AB The consistency of three density functional computational implementations (DMol, DGauss, and deMon) are compared with high-level Hartree-Fock and Moller-Plesset (MP) calculations for triazene (HN=NNH2) and formyl triazene (HN=NNHCOH). Proton affinities on all electronegative sites are investigated as well as the geometries of the neutral and protonated species. Density functional calculations employing the nonlocal gradient corrections show agreement with MP calculations for both proton affinities and geometries of neutral and protonated triazenes. Local spin density approximation DMol calculations using numerical basis sets must employ an extended basis to agree with other density functional codes using analytic Gaussian basis sets. The lowest energy conformation of triazene was found to be nonplanar; however, the degree of nonplanarity, as well as some bond lengths, is dependent on the basis set, electron correlation treatment, and methods used for the calculation. (C) 1994 by John Wiley and Sons, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702. UNIV LYON 1,INST PHYS NUCL,F-69622 VILLEURBANNE,FRANCE. RP SCHMIEDEKAMP, AM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 35 TC 16 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD AUG PY 1994 VL 15 IS 8 BP 875 EP 892 DI 10.1002/jcc.540150809 PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA NX408 UT WOS:A1994NX40800008 ER PT J AU NEWMAN, FL HOWARD, KI WINDLE, CD HOHMANN, AA AF NEWMAN, FL HOWARD, KI WINDLE, CD HOHMANN, AA TI INTRODUCTION TO THE SPECIAL SECTION ON SEEKING NEW METHODS IN MENTAL-HEALTH-SERVICES RESEARCH SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article AB Mental health services research aims ultimately to improve the quality, impact, and cost-effectiveness of services. Experience during the past decade suggests that the goals and study conditions of mental health services research require special methods. This special section presents 7 articles that give a flavor of the issues addressed and some of the methods that characterize this emerging research area. Although the series cannot explicate the full breadth or all the nuances of these methods, our goal is to entice colleagues to join us in developing methods for addressing services research questions. C1 NORTHWESTERN UNIV,EVANSTON,IL 60201. NIMH,BETHESDA,MD 20892. RP NEWMAN, FL (reprint author), FLORIDA INT UNIV,HLTH SERV ADM,N MIAMI CAMPUS,3000 NE 145TH ST,N MIAMI,FL 33181, USA. FU NIMH NIH HHS [R18 MH49157, K05 MH00924, R01 MH 42901] NR 13 TC 8 Z9 8 U1 0 U2 0 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 AUG PY 1994 VL 62 IS 4 BP 667 EP 669 DI 10.1037//0022-006X.62.4.667 PG 3 WC Psychology, Clinical SC Psychology GA PD281 UT WOS:A1994PD28100001 PM 7962869 ER PT J AU ISHIKAWA, K EANES, ED TUNG, MS AF ISHIKAWA, K EANES, ED TUNG, MS TI THE EFFECT OF SUPERSATURATION ON APATITE CRYSTAL-FORMATION IN AQUEOUS-SOLUTIONS AT PHYSIOLOGICAL PH AND TEMPERATURE SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE APATITES; CALCIFICATION; CRYSTAL SIZE; SUPERSATURATION; X-RAY DIFFRACTION ID NONSTOICHIOMETRIC APATITE; HYDROXYAPATITE CRYSTALS; CALCIUM PHOSPHATES; 37-DEGREES-C; ENAMEL; GROWTH; SATURATION; PHASE AB The importance of supersaturation in the dynamics of apatite precipitation from aqueous solutions is well-established. To determine whether this parameter has a comparable impact on the concomitant development of the textural properties of this phase, such as crystal size and shape, we investigated mineral accretion in synthetic solutions seeded with 0.67 g/L apatite over a range of supersaturations at pH 7.4 and 37 degrees C. A dual specific-ion electrode-controlled titration method was used to maintain the seeded reactions under the following solution conditions: 1.0 to 1.8 mmol/L Ca2+, 0.67 to 1.2 mmol/L total phosphate (PO4), Ca/PO4 (initial) = 1.5, 143 mmol/L KNO3, and 10 mmol/L HEPES. Samples were collected for chemical and textural analyses when the seed apatite was reduced by new accretions to 1/2, 1/4, 1/8, 1/16, and 1/32 of the total solids in suspension. All new accretions were found to be apatitic. At the lowest supersaturation, accretion occurred primarily by growth of the seed crystals. However, at the highest supersaturation examined, the crystals at the end of the experiments were actually smaller, on average, than the original seeds, even though the total mass increased 32-fold. The results suggest that proliferation of new crystals supplanted growth oi the seed crystals as supersaturation was increased. The results also suggest that differences in tissue fluid supersaturation may contribute to the large disparity in dimensions between dentin and enamel apatite crystals. C1 NIDR,BONE RES ASSOCIATE PROGRAM,GAITHERSBURG,MD 20899. NIST,AMER DENT ASSOC HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899. NR 27 TC 19 Z9 20 U1 0 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD AUG PY 1994 VL 73 IS 8 BP 1462 EP 1469 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PH563 UT WOS:A1994PH56300011 PM 8083444 ER PT J AU ROTEMYEHUDAR, R WINOGRAD, S SELA, S COLIGAN, JE EHRLICH, R AF ROTEMYEHUDAR, R WINOGRAD, S SELA, S COLIGAN, JE EHRLICH, R TI DOWN-REGULATION OF PEPTIDE TRANSPORTER GENES IN CELL-LINES TRANSFORMED WITH THE HIGHLY ONCOGENIC ADENOVIRUS-12 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; TOXIC LYMPHOCYTES-T; INTRACELLULAR-TRANSPORT; INFLUENZA HEMAGGLUTININ; MONOCLONAL-ANTIBODIES; SURFACE EXPRESSION; INTERFERON-GAMMA; MESSENGER-RNAS; VIRAL PEPTIDES AB The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2D(b) are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2D(b), but not H-2K(b), expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H-2D(b) and H-2K(b) expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo. C1 TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. NR 74 TC 70 Z9 70 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1994 VL 180 IS 2 BP 477 EP 488 DI 10.1084/jem.180.2.477 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NZ385 UT WOS:A1994NZ38500007 PM 7519239 ER PT J AU CHITNIS, CE MILLER, LH AF CHITNIS, CE MILLER, LH TI IDENTIFICATION OF THE ERYTHROCYTE BINDING DOMAINS OF PLASMODIUM-VIVAX AND PLASMODIUM-KNOWLESI PROTEINS INVOLVED IN ERYTHROCYTE INVASION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DUFFY-BLOOD-GROUP; FALCIPARUM-MALARIA PARASITES; RECEPTOR HETEROGENEITY; ANTIGEN; GLYCOPROTEIN; MEROZOITES; ANTIBODIES; EXPRESSION; FAMILY AB Plasmodium vivax and the related monkey malaria, P. knowlesi, require interaction with the Duffy blood group antigen, a receptor for a family of chemokines that includes interleukin 8, to invade human erythrocytes. One P. vivax and three P. knowlesi proteins that serve as erythrocyte binding ligands in such interactions share sequence homology. Expression of different regions of the P. vivax protein in COS7 cells identified a cysteine-rich domain that bound Duffy blood group-positive but not Duffy blood group-negative human erythrocytes. The homologous domain of the P. knowlesi proteins also bound erythrocytes, but had different specificities. The P. vivax and P. knowlesi binding domains lie in one of two regions of homology with the P. falciparum sialic acid binding protein, another erythrocyte binding ligand, indicating conservation of the domain for erythrocyte binding in evolutionarily distant malaria species. The binding domains of these malaria ligands represent potential vaccine candidates and targets for receptor-blockade therapy. C1 NIH,MALARIA RES LAB,BETHESDA,MD 20892. NR 29 TC 267 Z9 272 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1994 VL 180 IS 2 BP 497 EP 506 DI 10.1084/jem.180.2.497 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NZ385 UT WOS:A1994NZ38500009 PM 8046329 ER PT J AU PUNT, JA ROBERTS, JL KEARSE, KP SINGER, A AF PUNT, JA ROBERTS, JL KEARSE, KP SINGER, A TI STOICHIOMETRY OF THE T-CELL ANTIGEN RECEPTOR (TCR) COMPLEX - EACH TCR/CD3 COMPLEX CONTAINS ONE TCR-ALPHA, ONE TCR-BETA, AND 2 CD3-EPSILON CHAINS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODIES; THYMOCYTES; IDENTIFICATION; DETERMINANT; POPULATIONS; TOLERANCE; SUBUNITS; THYMUS AB The stoichiometry of the subunits that comprise the T cell antigen receptor (TCR) complex is not completely known. In particular, it is uncertain whether TCR alpha and TCR beta proteins are present in the TCR complex as one or multiple heterodimeric pairs. In this study we have used mice transgenic for two different TCR alpha and two different TCR beta proteins to determine the number of TCR alpha and TCR beta chains in a single TCR complex. Individual thymocytes and splenic T cells from double TCR transgenic mice simultaneously expressed all four transgenic TCR proteins on their surfaces. Because the individual TCR alpha and individual TCR beta proteins were biochemically distinguishable, we were able to examine associations among the transgenic TCR products. We found that each TCR alpha chain paired with each TCR beta chain, but that each TCR complex contained only one TCR alpha and one TCR beta protein. Furthermore, quantitative immunofluorescence revealed that T cells expressed twice as many CD3 epsilon as TCR beta proteins. These findings demonstrate that there are precisely one TCR alpha, one TCR beta, and two CD3 epsilon chains in each TCR/CD3 complex expressed on the surfaces of both thymocytes and mature T cells. RP PUNT, JA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. NR 27 TC 69 Z9 70 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1994 VL 180 IS 2 BP 587 EP 593 DI 10.1084/jem.180.2.587 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NZ385 UT WOS:A1994NZ38500018 PM 8046335 ER PT J AU HATHCOCK, KS LASZLO, G PUCILLO, C LINSLEY, P HODES, RJ AF HATHCOCK, KS LASZLO, G PUCILLO, C LINSLEY, P HODES, RJ TI COMPARATIVE-ANALYSIS OF B7-1 AND B7-2 COSTIMULATORY LIGANDS - EXPRESSION AND FUNCTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL ACTIVATION; ANTIGEN-PRESENTING CELLS; CTLA-4 COUNTER-RECEPTOR; B-CELLS; LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; IGD ANTIBODY; CD28; MOLECULE; B7/BB1 AB Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7-1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NIA, BETHESDA, MD 20892 USA. EOTVOS LORAND UNIV, DEPT IMMUNOL, H-2131 GODOLLO, HUNGARY. UNIV UDINE, SCH MED, DEPT SCI & BIOMED TECHNOL, I-33100 UDINE, ITALY. BRISTOL MYERS SQUIBB CO, PHARMACEUT RES INST, SEATTLE, WA 98121 USA. RI Pucillo, Carlo/A-5515-2008; OI Pucillo, Carlo/0000-0002-4872-6156 NR 57 TC 577 Z9 585 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1994 VL 180 IS 2 BP 631 EP 640 DI 10.1084/jem.180.2.631 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NZ385 UT WOS:A1994NZ38500023 PM 7519245 ER PT J AU CIARLET, M HIDALGO, M GORZIGLIA, M LIPRANDI, F AF CIARLET, M HIDALGO, M GORZIGLIA, M LIPRANDI, F TI CHARACTERIZATION OF NEUTRALIZATION EPITOPES ON THE VP7 SURFACE PROTEIN OF SEROTYPE G11 PORCINE ROTAVIRUSES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCES; MONOCLONAL-ANTIBODIES; GENOMIC CHARACTERIZATION; NUCLEOTIDE-SEQUENCE; SUBGROUP-I; STRAINS; SITES; GENE; SPECIFICITIES; LOCATION AB Rotavirus strain A253, isolated from the faeces of a diarrhoeic piglet in Venezuela, was classified as serotype G11 by cross-neutralization studies and by comparison of the deduced amino acid sequence of the VP7 surface protein. The epitopes involved in neutralization of the two G11 porcine rotavirus strains A253 and YM were analysed using neutralization-resistant mutants selected with seven neutralizing monoclonal antibodies (MAbs), monotype-specific (M-) MAbs and serotype-specific (S-) MAbs, produced against VP7 of strain A253. Cross-neutralization tests and sequence analysis of the escape mutants selected from strains A253 and YM indicated the presence of two antigenic sites, one common to both M-MAbs and S-MAbs in region A (positions 87, 91 and 96) and the other defined by one S-MAb in region C (position 223). All A253 variants selected with M-MAbs and two S-MAbs, although having different amino acid substitutions, had a change at amino acid position 87, whereas YM variants involved residues 91 and 96, part of the same antigenic site. Compared to strain A253, the YM strain presents an amino acid substitution at position 87 and was not recognized by M-MAbs. These results suggest that in the VP7 of G11 serotype specificity, the amino acid at position 87 is an important component of a neutralization site associated with region A and the intraserotypic variation between strains A253 and YM may account for the selection of mutations at different positions by a single MAb. C1 INST VENEZOLANO INVEST CIENT,BIOL VIRUS LAB,CARACAS,VENEZUELA. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 35 TC 44 Z9 44 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1994 VL 75 BP 1867 EP 1873 DI 10.1099/0022-1317-75-8-1867 PN 8 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA PA644 UT WOS:A1994PA64400006 PM 7519247 ER PT J AU WILSON, CA FARRELL, KB EIDEN, MV AF WILSON, CA FARRELL, KB EIDEN, MV TI COMPARISON OF CDNAS ENCODING THE GIBBON APE LEUKEMIA-VIRUS RECEPTOR FROM SUSCEPTIBLE AND NON-SUSCEPTIBLE MURINE CELLS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID C-TYPE VIRUS; LEUKEMIA-VIRUS; WILD MOUSE; ENVELOPE GLYCOPROTEINS; TISSUE DISTRIBUTION; GENE-TRANSFER; HOST RANGE; SUBGROUP-B; RETROVIRUS; INFECTION AB The gibbon ape leukaemia virus (GaLV) family of type C retroviruses consists of five closely related viral isolates, GaLV SF, GaLV SEATO, GaLV Br, GaLV H and simian sarcoma-associated virus. The cDNA encoding the human receptor for GaLV SEATO had previously been isolated. We now demonstrate that all of the above GaLVs can use the human form of the GaLV receptor to infect cells. All murine cells analysed to date have been found to be resistant to infection by GaLVs owing to the absence of a functional GaLV receptor. We have now identified a murine cell line which is unique in its susceptibility to GaLV infection. This cell line was established from a Japanese feral mouse, Mus musculus molossinus. We cloned and sequenced the cDNA for the receptor expressed in these cells and compared it to the cDNA for the GaLV receptor expressed in resistant murine cells such as NIH 3T3 (derived from M m. musculus) and MDTF (derived from M. dunni tail fibroblasts). The crucial region for GaLV infection (the fourth extracellular domain) from the functional M. m. molossinus GaLV receptor is quite divergent from the same region of the M. m. musculus and M. dunni proteins, but similar to that of the functional human GaLV receptor. These results confirm the importance of the amino acids of this region in GaLV receptor function. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 46 TC 31 Z9 32 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1994 VL 75 BP 1901 EP 1908 DI 10.1099/0022-1317-75-8-1901 PN 8 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA PA644 UT WOS:A1994PA64400010 PM 8046392 ER PT J AU RIMMELZWAAN, GF SIEBELINK, KHJ HUISMAN, RC MOSS, B FRANCIS, MJ OSTERHAUS, ADME AF RIMMELZWAAN, GF SIEBELINK, KHJ HUISMAN, RC MOSS, B FRANCIS, MJ OSTERHAUS, ADME TI REMOVAL OF THE CLEAVAGE SITE OF RECOMBINANT FELINE IMMUNODEFICIENCY VIRUS ENVELOPE PROTEIN FACILITATES INCORPORATION OF THE SURFACE GLYCOPROTEIN IN IMMUNE-STIMULATING COMPLEXES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID LYMPHOCYTES-T; ENV PROTEIN; CATS; ISCOM; INFECTION; VACCINATION; INDUCTION; INVIVO; CELLS AB Recombinant vaccinia viruses were constructed that expressed the complete env gene of feline immunodeficiency virus with or without the nucleotide sequence encoding the cleavage site between the surface (SU) protein and the transmembrane (TM) protein. The removal of this cleavage site resulted in the expression of a 150K protein that was processed into a 130K protein and was not cleaved into the SU and the TM proteins. Removal of the cleavage site also facilitated incorporation of the SU protein in immune-stimulating complexes (iscoms). Antibody responses to both an SU and a TM peptide representing two immunodominant B cell epitopes were measured. These were higher in cats immunized with iscoms prepared from the cleavage site-deleted envelope protein than in cats immunized with iscoms prepared from the native envelope protein or immunized with the envelope protein and the adjuvant Quil A. C1 ERASMUS UNIV ROTTERDAM,DEPT VIROL,3000 DR ROTTERDAM,NETHERLANDS. NATL INST PUBL HLTH & ENVIRONM PROTECT,IMMUNOBIOL LAB,3720 BA BILTHOVEN,NETHERLANDS. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. PITMAN MOORE LTD,UXBRIDGE UB9 6LS,MIDDX,ENGLAND. NR 27 TC 26 Z9 26 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1994 VL 75 BP 2097 EP 2102 DI 10.1099/0022-1317-75-8-2097 PN 8 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA PA644 UT WOS:A1994PA64400036 PM 8046415 ER PT J AU FRIED, MW FONG, TL SWAIN, MG PARK, Y BEAMES, MP BANKS, SM HOOFNAGLE, JH DIBISCEGLIE, AM AF FRIED, MW FONG, TL SWAIN, MG PARK, Y BEAMES, MP BANKS, SM HOOFNAGLE, JH DIBISCEGLIE, AM TI THERAPY OF CHRONIC HEPATITIS-B WITH A 6-MONTH COURSE OF RIBAVIRIN SO JOURNAL OF HEPATOLOGY LA English DT Article DE ANTIVIRAL AGENTS; CHRONIC HEPATITIS B; HEPATITIS B VIRUS; NUCLEOSIDE ANALOGS; RIBAVIRIN ID CONTROLLED TRIAL; PREDNISONE WITHDRAWAL; ALPHA-INTERFERON; VIRUS; MONOPHOSPHATE; EFFICACY; LIVER AB Ribavirin is a nucleoside analogue with broad spectrum antiviral activity that has been shown to inhibit viral replication in the woodchuck model of hepatitis B virus infection. We studied the effect of ribavirin on viral replication in 18 patients with chronic hepatitis B who were positive for hepatitis B e antigen. Patients were randomized to receive a 24-week course of oral ribavirin at a dose of either 800, 1000, or 1200 mg/kg per day. All patients completed 24 weeks of treatment and an additional 24 weeks of follow up without significant side effects except for mild, reversible hemolytic anemia. Response to ribavirin was similar among all three dosage groups (p>0.5); hence the data were pooled and analyzed together. Mean hepatitis B virus DNA levels decreased from 162.7 (95% confidence interval, 106 to 219) pg/ml before treatment to its lowest level of 114.3 (95% confidence interval, 53 to 175) pg/ml at week 20 (p<0.05). Two patients became negative for HBV DNA and lost hepatitis B e antigen. Mean serum alanine aminotransferase activity decreased markedly from 131.1 (95% confidence interval, 84 to 178) U/l before treatment to 62.4 (95% confidence interval, 48 to 77) U/l at the end of 24 weeks of ribavirin (p<0.05) and became normal in four patients (22%). Aminotransferase levels returned to baseline within 4 weeks once ribavirin was discontinued, while HBV DNA concentrations remained below baseline even at the end of 24 weeks of follow up. A 6-month course of oral ribavirin modestly inhibited viral replication and was associated with a marked decrease in alanine aminotransferase activity in patients with chronic hepatitis B. Ribavirin, alone, appears to be inadequate for the treatment of chronic hepatitis B, but it may ameliorate disease activity and may be useful as adjunctive therapy for this disease. (C) Journal of Hepatology. C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 28 TC 30 Z9 30 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD AUG PY 1994 VL 21 IS 2 BP 145 EP 150 DI 10.1016/S0168-8278(05)80387-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PD991 UT WOS:A1994PD99100002 PM 7989704 ER PT J AU PERDUE, TD BRODY, AR AF PERDUE, TD BRODY, AR TI DISTRIBUTION OF TRANSFORMING GROWTH-FACTOR-BETA-1, FIBRONECTIN, AND SMOOTH-MUSCLE ACTIN IN ASBESTOS-INDUCED PULMONARY FIBROSIS IN RATS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE ASBESTOS; TGF-BETA; FIBRONECTIN; SMOOTH MUSCLE ACTIN; INTERSTITIAL FIBROSIS ID BETA TGF-BETA; LUNG FIBROBLASTS; EXTRACELLULAR-MATRIX; ALVEOLAR MACROPHAGES; CHRYSOTILE ASBESTOS; IN-VITRO; DEPOSITION PATTERN; FIBROTIC LUNG; CELLS; EXPRESSION AB We are studying the development of fibrogenic lesions in the lungs of rats exposed briefly to an aerosol of chrysotile asbestos fibers. This model of asbestosis has enabled us to establish very early cellular events at the specific locations where interstitial fibrosis will develop. These sites, the first alveolar duct bifurcations, are where the fibers are initially deposited and where macrophages first accumulate. In the studies presented here, we used immunohistochemical techniques to show that these macrophages exhibit strong localization of transforming growth factor-beta. In the adjacent developing fibrogenic lesions a clear increase in fibronectin staining was demonstrated and morphological analysis indicated a significant increase in amounts of smooth muscle actin. Such studies are essential in furthering out understanding of the distribution of potential mediators of the fibrogenic process and the cellular responses they elicit during the pathogenesis of disease. C1 TULANE UNIV,MED CTR,DEPT PATHOL & LAB MED,NEW ORLEANS,LA 70112. NATL INST ENVIRONM HLTH SCI,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC. NR 61 TC 51 Z9 52 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 1994 VL 42 IS 8 BP 1061 EP 1070 PG 10 WC Cell Biology SC Cell Biology GA NY890 UT WOS:A1994NY89000004 PM 8027525 ER PT J AU MURPHY, WJ DURUM, SK ANVER, MR FERRIS, DK MCVICAR, DW OSHEA, JJ RUSCETTI, SK SMITH, MR YOUNG, HA LONGO, DL AF MURPHY, WJ DURUM, SK ANVER, MR FERRIS, DK MCVICAR, DW OSHEA, JJ RUSCETTI, SK SMITH, MR YOUNG, HA LONGO, DL TI INDUCTION OF T-CELL DIFFERENTIATION AND LYMPHOMAGENESIS IN THE THYMUS OF MICE WITH SEVERE COMBINED IMMUNE-DEFICIENCY (SCID) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TCR-BETA-CHAIN; V(D)J RECOMBINATION; TISSUES; SURFACE; DEFECT; GENES; MOUSE; ALPHA; DELTA AB Severe combined immune deficiency (SCID) mice have a defect in their recombinase system and cannot productively rearrange their immune receptor genes, Thus, SCID thymocytes are arrested at the immature ''triple negative'' phase, not expressing CD3, CD4, or CD8 surface markers. Whole body irradiation of SCID mice induced maturation of their thymocytes to the CD4(+)/CD8(+) double positive, CD3(+low) stage of differentiation, and resulted in the generation of a thymic cortical region on histologic examination. No mature single positive T cells were detected in the thymus or the periphery. VDI rearrangements of TCR-beta with restricted clonality were observed in the double positive cells from a given individual. The CD3 complex was expressed on some of these cells, but the cells failed to mobilize intracellular calcium after cross-linking with CD3 Abs. The double positive cells appeared several weeks after irradiation, persisted for many months in the thymus, and by 6 mo generally developed into metastatic lymphoma. Retroviral activation was undetectable in both the preneoplastic and transformed thymocytes. Thus, it appears that the earliest steps in T cell development can be induced in SCID mice by inducing DNA breaks with radiation. This system represents a model of early thymic development, preneoplasia, and neoplasia. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,DIV CANC ETIOL,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015 NR 17 TC 55 Z9 54 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1994 VL 153 IS 3 BP 1004 EP 1014 PG 11 WC Immunology SC Immunology GA NY342 UT WOS:A1994NY34200011 PM 7913108 ER PT J AU SNYDER, JG DINH, Q MORRISON, SL PADLAN, EA MITCHELL, M YULEE, LY MARCUS, DM AF SNYDER, JG DINH, Q MORRISON, SL PADLAN, EA MITCHELL, M YULEE, LY MARCUS, DM TI STRUCTURE-FUNCTION STUDIES OF ANTI-3-FUCOSYLLACTOSAMINE (LE(X)) AND GALACTOSYLGLOBOSIDE ANTIBODIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ANTIGEN-BINDING; COMBINING SITES; VH-GENE; ORBITAL ELECTRONEGATIVITY; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSE; LIGHT CHAIN; GLYCOSYLATION; HEAVY AB We are studying murine mAbs against two carbohydrate epitopes, 3-fucosyllactosamine (Le(x), CD15) and galactosylgloboside. The V-H domains of both panels of Ab are encoded by V(H)441, a member of the X24 family of Ig genes. To evaluate the contribution of the heavy chain CDR3 to the affinity of the anti-3-fucosyllactosamine Ab, CDR3-H of PMN6, a low affinity Ab, was replaced by the CDR3 of PM81, a higher affinity Ab. The affinity of the chimeric 6/81 Ab was increased when the heavy chain was paired with the PM81 light chain, but not when paired with another light chain (M5), which differs from PM81 light chain by three amino acids. To evaluate the contribution of somatic mutations to the binding of GalGb4, the 3A9 V-H sequence, which contains three amino acid substitutions, was replaced by a germ-line sequence encoded by either V(H)441 or V(H)X24. The chimeric Ab, 441/3A9 and X24/3A9, bound Ag as well as the wild-type 3A9 Ab. Computer models of the Fv fragments of PM81 and 3A9 were compared with the crystal structure of the Fv fragment of J539, a galactan-binding myeloma protein that is encoded by the same V-H and V-K genes as 3A9. The surfaces of 3A9 and J539 have shallow pockets that are potential Ag-binding sites. Replacement of CDR3-H Tyr99, which is a prominent component of the pocket, by Ala abolished the binding of Ag. In contrast, the Fv surface of PM81 contains a large cleft rather than a pocket. These models indicate how the same V-H gene segment can be used to encode Abs that exhibit different specificities. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. BECTON DICKINSON RES CTR,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA16858]; NIAID NIH HHS [AI29470, AI 17712] NR 36 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1994 VL 153 IS 3 BP 1161 EP 1170 PG 10 WC Immunology SC Immunology GA NY342 UT WOS:A1994NY34200026 PM 7913110 ER PT J AU MARINCOLA, FM SHAMAMIAN, P ALEXANDER, RB GNARRA, JR TURETSKAYA, RL NEDOSPASOV, SA SIMONIS, TB TAUBENBERGER, JK YANNELLI, J MIXON, A RESTIFO, NP HERLYN, M ROSENBERG, SA AF MARINCOLA, FM SHAMAMIAN, P ALEXANDER, RB GNARRA, JR TURETSKAYA, RL NEDOSPASOV, SA SIMONIS, TB TAUBENBERGER, JK YANNELLI, J MIXON, A RESTIFO, NP HERLYN, M ROSENBERG, SA TI LOSS OF HLA HAPLOTYPE AND B-LOCUS DOWN-REGULATION IN MELANOMA CELL-LINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN-MALIGNANT MELANOMA; I ANTIGEN EXPRESSION; COMPLEX CLASS-I; MONOCLONAL-ANTIBODY; RESTRICTION ELEMENT; SOLID TUMORS; TNF LOCUS; T-CELLS; GENE AB The expression of HLA class I molecules on tumor cells is vital for CD8(+) T cell recognition of tumor Ags. Loss of HLA class I Ag expression as a result of defective beta(2)-microglobulin genes has been described in melanoma cells. To further evaluate mechanisms of tumor escape, HLA class I Ag expression was compared in 24 metastatic melanoma cell lines and 20 melanocyte strains by FACS analysis with use of allele-specific mAbs. Total loss of HLA class I Ag expression was not noted; instead, two relatively common phenomena were identified: 1) A variable degree of expression of HLA-B Ags by melanoma cell lines and melanocytes; however, HLA-A Ags were consistently expressed in all cell types. Furthermore, HLA-B locus Ag expression was detected in vivo in only one of six frozen section specimens obtained from six patients having metastatic melanoma. 2) Loss of allelic expression was noted in two of 14 HLA-A2 (14%) and one of three HLA-A29 (33%) melanoma cell lines and included a full haplotype, which suggests loss of a genomic fragment. Allele-specific PCR amplification demonstrated deletion of genes in linkage disequilibrium within the MHC class II, III, and I regions. Aberrations of HLA class I expression in tumor lines should be considered when assessing MHC-restricted phenomena in in vitro models. C1 NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. WISTAR INST ANAT & BIOL,DEPT ANAT,PHILADELPHIA,PA 19106. RP MARINCOLA, FM (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016; OI Restifo, Nicholas P./0000-0003-4229-4580 NR 64 TC 149 Z9 150 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1994 VL 153 IS 3 BP 1225 EP 1237 PG 13 WC Immunology SC Immunology GA NY342 UT WOS:A1994NY34200033 PM 8027550 ER PT J AU NISHIMURA, MI KAWAKAMI, Y CHARMLEY, P ONEIL, B SHILYANSKY, J YANNELLI, JR ROSENBERG, SA HOOD, L AF NISHIMURA, MI KAWAKAMI, Y CHARMLEY, P ONEIL, B SHILYANSKY, J YANNELLI, JR ROSENBERG, SA HOOD, L TI T-CELL RECEPTOR REPERTOIRE IN TUMOR-INFILTRATING LYMPHOCYTES - ANALYSIS OF MELANOMA-SPECIFIC LONG-TERM LINES SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE T-CELL RECEPTOR; MELANOMA; TUMOR-INFILTRATING LYMPHOCYTES ID BETA-GENE USAGE; SYNGENEIC MURINE LEUKEMIA; METASTATIC MELANOMA; V-ALPHA; ADOPTIVE IMMUNOTHERAPY; LIMITED HETEROGENEITY; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; MYASTHENIA-GRAVIS; PERIPHERAL-BLOOD AB Cytotoxic T-lymphocytes (CTLs) can be isolated from human melanoma biopsies that specifically lyse autologous melanoma in vitro and can be effective therapeutic agents for patients with advanced disease. Recent evidence indicates that HLA-A2-restricted, melanoma-specific tumor-infiltrating lymphocytes (TILs) recognize melanomas obtained from different HLA-A2(+) patients, suggesting the presence of one or more common melanoma antigens. Furthermore, T-cell receptor (TCR) repertoire analysis by other groups of TILs from fresh melanoma biopsies suggests that there is limited TCR V gene usage in TILs. One serious limitation in analyzing the TCR repertoire in fresh tumors has been the inability to correlate TCR usage with immune function. Therefore, the TCR repertoire was determined in long-term TIL cultures that specifically lysed autologous melanoma in vitro and in many cases mediated in vivo regression of metastatic cancer in patients with advanced disease. The TCR repertoire in cultured melanoma-specific TILs was diverse, with each TIL containing an average of 9.5 +/- 5.7 of the 23 V alpha and 11.2 +/- 5.9 of the 23 V beta subfamilies. Despite the large diversity observed, several V alpha and V beta genes (V alpha 1, V alpha 2, V alpha 22, V beta 13, V beta 14, and V beta 18) are very commonly found in melanoma-specific TILs. No statistically significant associations were observed between the presence of a TCR V gene subfamily in TILs and clinical response, HLA haplotype, or age of the culture. Even though the results in this study suggest that certain TCR V gene segments may be involved in immune responses to human melanoma, we were unable to demonstrate functionally that a particular T-cell clonotype recognizes melanoma tumor-associated antigens. Only the analysis of melanoma-specific CTL clones can determine which clonotypes are important in lysis of human melanoma. C1 CALTECH,DIV BIOL,PASADENA,CA 91125. RP NISHIMURA, MI (reprint author), NCI,SURG BRANCH,BLDG 10,RM 2B04,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 61 TC 36 Z9 36 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD AUG PY 1994 VL 16 IS 2 BP 85 EP 94 DI 10.1097/00002371-199408000-00002 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PG913 UT WOS:A1994PG91300002 PM 7804531 ER PT J AU HUGHES, JM LAMONTAGNE, JR AF HUGHES, JM LAMONTAGNE, JR TI EMERGING INFECTIOUS-DISEASES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP HUGHES, JM (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,1600 CLIFTON RD,MAILSTOP C12,ATLANTA,GA 30333, USA. NR 20 TC 11 Z9 11 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 AUG PY 1994 VL 170 IS 2 BP 263 EP 264 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700002 PM 8035007 ER PT J AU KRAUSE, RM AF KRAUSE, RM TI DYNAMICS OF EMERGENCE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 17-18, 1993 CL NEW ORLEANS, LA SP INFECTIOUS DIS SOC AMER ID STAPHYLOCOCCUS-AUREUS; CAPSULAR POLYSACCHARIDES; INFECTIONS; FEVER RP KRAUSE, RM (reprint author), NIH,FOGARTY INT CTR,9000 ROCKVILLE PIKE,BLDG 31,RM B2C02,BETHESDA,MD 20892, USA. NR 32 TC 27 Z9 27 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1994 VL 170 IS 2 BP 265 EP 271 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700003 PM 8035008 ER PT J AU JANOFF, EN JACKSON, S WAHL, SM THOMAS, K PETERMAN, JH SMITH, PD AF JANOFF, EN JACKSON, S WAHL, SM THOMAS, K PETERMAN, JH SMITH, PD TI INTESTINAL MUCOSAL IMMUNOGLOBULINS DURING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROWTH-FACTOR-BETA; HIV-INFECTION; PERIPHERAL-BLOOD; ANTIBODY-RESPONSES; T-CELLS; MONONUCLEAR-CELLS; IGA ANTIBODIES; MONOMERIC IGA; LYMPHOCYTES-B; IMMUNE-SYSTEM AB In intestinal fluid samples from 39 human immunodeficiency virus type 1 (HIV-1)-infected patients, IgA and IgG levels were equivalent, whereas in 10 controls, IgA levels were significantly higher than those of IgG (P < .05). Intestinal IgA in patients contained predominantly monomeric IgA1, whereas IgA1 and IgA2 subclass levels in controls were nearly equivalent and primarily polymeric. The predominance of IgG and monomeric IgA1 in mucosal fluid samples from HIV-1-infected patients suggests exudation of serum immunoglobulins into the intestine. The decreased proportion of mucosal plasma cells producing IgA and IgA2 in the HIV-1-infected patients (P < .01) may also contribute to the abnormal intestinal immunoglobulin levels. Intestinal IgG reacted with most HIV-1 antigens, whereas specific IgA was present in only 10 of 17 patients and reacted with only envelope (gp120 and gp160) and, less often, core (p17 and p24) antigens. Aberrant mucosal antibody responses and decreased integrity of the mucosal barrier may contribute to the intestinal dysfunction and infections that characterize HIV-1 infection. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. RP JANOFF, EN (reprint author), UNIV MINNESOTA,SCH MED,VET AFFAIRS MED CTR,DEPT MED,INFECT DIS SECT 111F,1 VET DR,MINNEAPOLIS,MN 55417, USA. FU NIAID NIH HHS [AI-23952, AI-31373]; NIDDK NIH HHS [DK-47322] NR 78 TC 61 Z9 61 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 AUG PY 1994 VL 170 IS 2 BP 299 EP 307 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700009 PM 8035014 ER PT J AU SEI, S KLEINER, DE KOPP, JB CHANDRA, R KLOTMAN, PE YARCHOAN, R PIZZO, PA MITSUYA, H AF SEI, S KLEINER, DE KOPP, JB CHANDRA, R KLOTMAN, PE YARCHOAN, R PIZZO, PA MITSUYA, H TI QUANTITATIVE-ANALYSIS OF VIRAL BURDEN IN TISSUES FROM ADULTS AND CHILDREN WITH SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION ASSESSED BY POLYMERASE CHAIN-REACTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; BLOOD MONONUCLEAR-CELLS; CENTRAL NERVOUS-SYSTEM; PERIPHERAL-BLOOD; HIV-INFECTION; PROVIRAL DNA; LYMPH-NODES; T-CELL; NEUTRALIZING ANTIBODIES AB The amount of human immunodeficiency virus type 1 (HIV-1) in various tissues was investigated by polymerase chain reaction (PCR) in 16 patients with end-stage HIV-1 infection and 7 patients with symptomatic but less advanced disease. During postmortem study of the 16 endstage patients, HIV-1 DNA was found most often in lymph nodes and the spleen (both 100%), lung (93.8%), and colon (87.5%). Biopsied lymph nodes from the 7 symptomatic patients contained substantially higher copy numbers of HIV-1 RNA and DNA than did peripheral blood mononuclear cells (PBMC). Plasma viral RNA levels correlated significantly with the amount of HIV-1 RNA in PBMC (r(2) = .86, P = .0025) but not with the level of viral RNA in lymph nodes in patients with symptomatic HIV-1 infection. These data suggest that although lymph nodes represent the main site for HIV-1 infection and replication, the level of circulating viral burden may not be solely determined by the magnitude of active HIV-1 replication in lymph nodes. C1 NCI,PATHOL LAB,MED BRANCH,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. RP SEI, S (reprint author), NCI,PATHOL LAB,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Kleiner, David/0000-0003-3442-4453; Kopp, Jeffrey/0000-0001-9052-186X NR 54 TC 40 Z9 40 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1994 VL 170 IS 2 BP 325 EP 333 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700013 PM 8035018 ER PT J AU NISHIMURA, M KERMODE, AG CLERICI, M SHEARER, GM BERZOFSKY, JA UCHIYAMA, T WIKTOR, SZ PATE, E MALONEY, B MANNS, A BLATTNER, W JACOBSON, S AF NISHIMURA, M KERMODE, AG CLERICI, M SHEARER, GM BERZOFSKY, JA UCHIYAMA, T WIKTOR, SZ PATE, E MALONEY, B MANNS, A BLATTNER, W JACOBSON, S TI DEMONSTRATION OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I)-SPECIFIC T-CELL RESPONSES FROM SERONEGATIVE AND POLYMERASE CHAIN REACTION-NEGATIVE PERSONS EXPOSED TO HTLV-I SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SPASTIC PARAPARESIS; CHILD TRANSMISSION; LEUKEMIA LYMPHOMA; MYCOSIS-FUNGOIDES; IMMUNE-RESPONSE; ANTIBODIES; MYELOPATHY; RETROVIRUSES; LYMPHOCYTES; TAX AB Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to adult T cell leukemia and the progressive chronic neurologic disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Described is a method that measures the production of interleukin-2 from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I-infected persons. The peptides correspond to immunogenic regions of the HTLV-I Env and Tax proteins. Significantly, this assay demonstrated T cell responses to these HTLV-I peptides from coded PBL samples in 7 of 19 HTLV-I-seronegative polymerase chain reaction-negative persons known to have been exposed to HTLV-I but in none of 16 matched controls without risk factors for exposure (P = .007). The implications of this finding are discussed. C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,METAB & VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. KYOTO UNIV,INST VIRAL RES,KYOTO 606,JAPAN. NR 23 TC 10 Z9 10 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 AUG PY 1994 VL 170 IS 2 BP 334 EP 338 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700014 PM 8035019 ER PT J AU HSING, AW SCHIFFMAN, M ZHANG, T GREER, CE CHEN, CJ YOU, SL HSIEH, CY HUANG, TW LIAW, KL MANES, M AF HSING, AW SCHIFFMAN, M ZHANG, T GREER, CE CHEN, CJ YOU, SL HSIEH, CY HUANG, TW LIAW, KL MANES, M TI PERSISTENCE OF TYPE-SPECIFIC HUMAN PAPILLOMAVIRUS INFECTION AMONG CYTOLOGICALLY NORMAL WOMEN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 ROCHE MOLEC SYST,ALAMEDA,CA. NATL TAIWAN UNIV HOSP,TAIPEI,TAIWAN. TAIPEI INST PATHOL,TAIPEI,TAIWAN. RP HSING, AW (reprint author), NCI,BIOSTAT BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EPN ROOM 415,BETHESDA,MD 20892, USA. RI Chen, Chien-Jen/C-6976-2008 NR 3 TC 5 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1994 VL 170 IS 2 BP 498 EP 498 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NZ467 UT WOS:A1994NZ46700046 PM 8035046 ER PT J AU DING, M GANNETT, PM ROJANASAKUL, Y LIU, KJ SHI, XL AF DING, M GANNETT, PM ROJANASAKUL, Y LIU, KJ SHI, XL TI ONE-ELECTRON REDUCTION OF VANADATE BY ASCORBATE AND RELATED FREE-RADICAL GENERATION AT PHYSIOLOGICAL PH SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; VANADIUM; OXYGEN; DNA; NADH; ESR; COOXYGENATION; OXIDATION; INVITRO AB The one-electron reduction of vanadate (vanadium(V)) by ascorbate and related free radical generation at physiological pH was investigated by ESR and ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Incubation of vanadium(V) with ascorbate generated significant amounts of vanadium(IV) in phosphate buffer (pH 7.4) but not in sodium cacodylate buffer (pH 7.4) nor in water. The vanadium(IV) yield increased with increasing ascorbate concentration, reaching a maximum at a vanadium(V): ascorbate ratio of 2:1. Addition of formate to the incubation mixture containing vanadium(V), ascorbate, and phosphate generated carboxylate radical (.COO-), indicating the formation of reactive species in the vanadium(V) reduction mechanism. In the presence of H2O2, a mixture of vanadium(V), ascorbate, and phosphate buffer generated hydroxyl radical (.OH) via a Fenton-like reaction (vanadium(IV)+ H2O2 --> vanadium(V) + .OH + OH-). The .OH yield was favored at relatively low ascorbate concentrations. Omission of phosphate sharply reduced the OH yield. The vanadium(IV) generated by ascorbate reduction of vanadium(V) in the presence of phosphate was also capable of generating lipid hydroperoxide-derived free radicals from cumene hydroperoxide, a model lipid hydroperoxide. Because of the ubiquitous presence of ascorbate in cellular system at relatively high concentrations, one-electron reduction of vanadium(V) by ascorbate together with phosphate may represent an important vanadium(V) reduction pathway in vivo. The resulting reactive species generated by vanadium(IV) from H2O2 and lipid hydroperoxide via a Fenton-like reaction may play a significant role in the mechanism of vanadium(V)-induced cellular injury. C1 NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. W VIRGINIA UNIV,DEPT IMMUNOL & MICROBIOL,MORGANTOWN,WV 26506. W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506. DARTMOUTH COLL,DEPT RADIOL,HANOVER,NH 03755. RI Shi, Xianglin/B-8588-2012; Gannett, Peter/J-3347-2015; OI Gannett, Peter/0000-0002-7859-5468; Rojanasakul, Yon/0000-0002-8839-6462 NR 43 TC 40 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD AUG 1 PY 1994 VL 55 IS 2 BP 101 EP 112 DI 10.1016/0162-0134(94)85032-1 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA NW852 UT WOS:A1994NW85200003 PM 8051539 ER PT J AU STEIS, RG LONGO, DL AF STEIS, RG LONGO, DL TI CLINICAL RELEVANCE OF RECOMBINANT INTERFERON-ALPHA(2A) ANTIBODIES IN PATIENTS WITH HAIRY-CELL LEUKEMIA SO JOURNAL OF INTERFERON RESEARCH LA English DT Article; Proceedings Paper CT 1994 European Interferon Workshop on Antagonists and Antibodies to Interferons and Other Therapeutically Used Human Proteins CY FEB 16-18, 1994 CL HANNOVER, GERMANY C1 NCI,FREDERICK CANC RES FACIL,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP STEIS, RG (reprint author), GEORGIA ONCOL & HEMATOL CLIN,3200 DOWNWOOD CIRCLE,SUITE 125,ATLANTA,GA 30342, USA. NR 3 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0197-8357 J9 J INTERFERON RES JI J. Interferon Res. PD AUG PY 1994 VL 14 IS 4 BP 207 EP 209 DI 10.1089/jir.1994.14.207 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD999 UT WOS:A1994PD99900023 PM 7822877 ER PT J AU KIM, IG LEE, SC LEE, JH YANG, JM CHUNG, SI STEINERT, PM AF KIM, IG LEE, SC LEE, JH YANG, JM CHUNG, SI STEINERT, PM TI STRUCTURE AND ORGANIZATION OF THE HUMAN TRANSGLUTAMINASE-3 GENE - EVOLUTIONARY RELATIONSHIP TO THE TRANSGLUTAMINASE FAMILY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE TRANSGLUTAMINASE 2; CELL ENVELOPE; KERATINIZATION ID BLOOD-COAGULATION FACTOR; HUMAN FACTOR-XIII; KERATINOCYTE TRANSGLUTAMINASE; PROTRANSGLUTAMINASE-E; CELL-DEATH; SEQUENCE; SUBUNIT; PROTEIN; APOPTOSIS AB The human haploid genome contains a family of at least five different transglutaminases that are differentially expressed in time- and tissue-specific ways. Of these, transglutaminase 3 (TGase3) is unusual in that it is a pro-enzyme requiring activation by proteolysis. To date it is known to be expressed only in terminally differentiating epidermal and hair follicle keratinocytes. In this paper we show that it is encoded by a gene (TGM3) of 42.8 kbp containing 13 exons. In the course of isolation of genomic clones for the TGM3 gene, we also found clones encoding the widely expressed tissue or TGase2 enzyme, perhaps due to high degrees of sequence homology. The structure of the TGM2 gene has not yet been reported. Our incomplete data suggest its exon/intron organization is very similar to that of TGM3. Although the common intron splice points of all members of the transglutaminase gene family have been conserved, the TGM3 and TGM2 genes, and the gene for the subplasma membrane transglutaminase-like protein band 4.2, lack two introns found in the TGM1 and factor XIIIa genes, and the exact intron splice point of another intron is shifted with respect to that of the TGM1 and factor XIIIa genes. Based on sequence homologies and gene structures, the data support a phylogenic tree in which the TGM2 and TGM3 genes belong on a branch distinct from other transglutaminases. C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 34 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1994 VL 103 IS 2 BP 137 EP 142 DI 10.1111/1523-1747.ep12392470 PG 6 WC Dermatology SC Dermatology GA NZ389 UT WOS:A1994NZ38900001 PM 7913719 ER PT J AU PLOTT, RT AMAGAI, M UDEY, MC STANLEY, JR AF PLOTT, RT AMAGAI, M UDEY, MC STANLEY, JR TI PEMPHIGUS-VULGARIS ANTIGEN LACKS BIOCHEMICAL-PROPERTIES CHARACTERISTIC OF CLASSICAL CADHERINS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE DESMOGLEIN; CATENINS; PLAKOGLOBIN; DESMOSOME ID CELL-ADHESION MOLECULES; UVOMORULIN-CATENIN COMPLEX; BETA-CATENIN; CYTOPLASMIC DOMAIN; DESMOSOMAL GLYCOPROTEIN; PLAKOGLOBIN; IDENTIFICATION; DISTINCT; FAMILY; DESMOGLEIN AB Pemphigus vulgaris antigen (PVA) is a member of the desmoglein subfamily of the cadherin supergene family. PVA has homology to the classical cadherins (e.g., E-cadherin), both in its extracellular and cytoplasmic domains. Classical cadherins possess certain well-defined and characteristic biochemical properties of both domains. The cytoplasmic domain binds alpha-, beta-, and gamma-catenins. The extracellular domain is protected by calcium from degradation by trypsin. In this study we show that PVA does not share these characteristic biochemical features. Immunoprecipitation of E-cadherin and PVA from human keratinocytes shows that under the same conditions in which the catenins co-precipitate with E-cadherin, only plakoglobin (which co-migrates with gamma-catenin) co-precipitates with PVA. Treatment of keratinocytes with 0.01% trypsin in 1 mM calcium (T/C) does not degrade the extracellular region of E-cadherin, but does partially degrade that of PVA. This increased T/C susceptibility of PVA is not due to its cytoplasmic domain, as the same sensitivity of the extracellular domain of PVA to T/C was observed in L cell clones transfected with a chimeric cDNA that encoded for the extracellular domain of PVA and the cytoplasmic domain of E-cadherin. These data demonstrate that although the desmogleins and classical cadherins share striking amino acid homologies in both the cytoplasmic and extracellular domains, they do not exhibit identical biochemical properties and, by extension, may not subserve identical cell biologic functions. C1 NIH,DERMATOL BRANCH,BETHESDA,MD 20892. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 40 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1994 VL 103 IS 2 BP 168 EP 172 DI 10.1111/1523-1747.ep12392642 PG 5 WC Dermatology SC Dermatology GA NZ389 UT WOS:A1994NZ38900007 PM 8040605 ER PT J AU COMPTON, JG GOLDSTEIN, AM TURNER, M BALE, AE KEARNS, KS MCBRIDE, OW BALE, SJ AF COMPTON, JG GOLDSTEIN, AM TURNER, M BALE, AE KEARNS, KS MCBRIDE, OW BALE, SJ TI FINE MAPPING OF THE LOCUS FOR NEVOID BASAL-CELL CARCINOMA SYNDROME ON CHROMOSOME 9Q SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE GORLIN SYNDROME; BASAL CELL NEVUS SYNDROME; NBCCS; GENE MAPPING; LINKAGE ANALYSIS ID DINUCLEOTIDE REPEAT POLYMORPHISM; GORLIN SYNDROME; GENE; FAMILIES; LINKAGE; LOCALIZATION; MAP AB The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized primarily by multiple basal cell carcinomas, odontogenic keratocysts, and pits of the palms and soles. Tumor deletion studies and linkage analysis in Caucasians have revealed that the gene is on chromosome 9q. To further refine the location of the nevoid basal cell carcinoma syndrome locus, we tested linkage to this region in three families. Evaluation of recombinants suggested that the nevoid basal cell carcinoma syndrome locus lies in the interval defined distally by D9S127. Our data, together with existing published data defining D9S12 as a proximal flanking marker, refine the location of nevoid basal cell carcinoma syndrome to an 8.3-cM interval. Two of the families studied were African-American and show a notable variation in phenotypic expression in which affected individuals developed few skin cancers. However, despite clinical heterogeneity, our data are consistent with the hypothesis that the same locus is involved in these African-American families. C1 NCI,DIV CANC BIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,DERMATOL BRANCH,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. NCI,DIV CANC BIOL DIAG & CTR,BIOCHEM LAB,BETHESDA,MD 20892. RP COMPTON, JG (reprint author), NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BLDG 6,ROOM 429,BETHESDA,MD 20892, USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1994 VL 103 IS 2 BP 178 EP 181 DI 10.1111/1523-1747.ep12392682 PG 4 WC Dermatology SC Dermatology GA NZ389 UT WOS:A1994NZ38900009 PM 8040607 ER PT J AU TAITELBAUM, H FERRETTI, JA SPENCER, RGS WEISS, GH AF TAITELBAUM, H FERRETTI, JA SPENCER, RGS WEISS, GH TI OPTIMIZATION OF 2-STAGE MEASUREMENTS OF T-1 SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID INVERSION-RECOVERY EXPERIMENTS; STOCHASTIC SIMULATION; STATISTICAL-ANALYSIS; NMR RELAXATION; T1 AB A recent analysis of the optimization of adaptive T-1 measurements based on inversion-recovery (IR) experiments is extended to allow for the use of fast-inversion-recovery (FIR) experiments in either of the two stages of the experiment. FIR experiments can be carried out more quickly than IR experiments but individual measurements are inherently less precise. Both types of experiments are considered, with a fixed number of times at which measurements are made and with a fixed total running time. The results of the investigation suggest that an optimal two-stage experiment with a fixed number of measurements makes use of the FIR technique in the first stage and IR in the second. When the total running time is fixed, it is generally better to use FIR in both stages. (C) 1994 Academic Press, Inc. C1 NHLBI, BIOPHYS CHEM LAB, BETHESDA, MD 20892 USA. NIA, MOLEC & CELLULAR BIOL LAB, BALTIMORE, MD 21224 USA. RP TAITELBAUM, H (reprint author), NHLBI, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NR 12 TC 6 Z9 6 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD AUG PY 1994 VL 109 IS 2 BP 166 EP 171 DI 10.1006/jmra.1994.1150 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA PB546 UT WOS:A1994PB54600004 ER PT J AU TOMAREV, SI DUNCAN, MK ROTH, HJ CVEKL, A PIATIGORSKY, J AF TOMAREV, SI DUNCAN, MK ROTH, HJ CVEKL, A PIATIGORSKY, J TI CONVERGENT EVOLUTION OF CRYSTALLIN GENE-REGULATION IN SQUID AND CHICKEN - THE AP-1 ARE CONNECTION SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE LENS; CRYSTALLIN; SQUID; CHICKEN; GENE; REGULATION; AP-1; EVOLUTION ID GLUTATHIONE-S-TRANSFERASE; ANTIOXIDANT RESPONSIVE ELEMENT; DNA-BINDING ACTIVITY; HEAT-SHOCK PROTEIN; ALPHA-B-CRYSTALLIN; LENS CRYSTALLINS; C-JUN; SUBUNIT GENE; PHYSICOCHEMICAL CHARACTERIZATION; CUBOMEDUSAN JELLYFISH AB Previous experiments have shown that the minimal promoters required for function of the squid SL20-1 and SL11 crystallin genes in transfected rabbit lens epithelial cells contain an overlapping AP-1/antioxidant responsive element (ARE) upstream of the TATA box. This region resembles the PL-1 and PL-2 elements of the chicken beta B1-crystallin promoter which are essential for promoter function in transfected primary chicken lens epithelial cells. Here we demonstrate by site-directed mutagenesis that the AP-1/ARE sequence is essential for activity of the squid SL20-1 and SL11 promoters in transfected embryonic chicken lens cells and fibroblasts. Promoter activity was higher in transfected lens cells than in fibroblasts. Electrophoretic mobility shift and DNase protection experiments demonstrated the formation of numerous complexes between nuclear proteins of the embryonic chicken lens and the AP-1/ARE sequences of the squid SL20-1 and SL11 crystallin promoters. One of these complexes comigrated and cross-competed with that formed with the PL-1 element of the chicken beta B1-crystallin promoter. This complex formed with nuclear extracts from the lens, heart, brain, and skeletal muscle of embryonic chickens and was eliminated by competition with a consensus AP-1 sequence. The nonfunctional mutant AP-1/ARE sequences did not compete for complex formation. These data raise the intriguing possibility that entirely different, nonhomologous crystallin genes of the chicken and squid have convergently evolved a similar cisacting regulatory element (AP-1/ARE) for high expression in the lens. RP NEI, MOLEC & DEV BIOL LAB, BLDG 6, ROOM 203, BETHESDA, MD 20892 USA. RI Cvekl, Ales/B-2427-2013 NR 67 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 EI 1432-1432 J9 J MOL EVOL JI J. Mol. Evol. PD AUG PY 1994 VL 39 IS 2 BP 134 EP 143 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA NX168 UT WOS:A1994NX16800004 PM 7932777 ER PT J AU LOPEZ, JV YUHKI, N MASUDA, R MODI, W OBRIEN, SJ AF LOPEZ, JV YUHKI, N MASUDA, R MODI, W OBRIEN, SJ TI NUMT, A RECENT TRANSFER AND TANDEM AMPLIFICATION OF MITOCHONDRIAL-DNA TO THE NUCLEAR GENOME OF THE DOMESTIC CAT SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE MITOCHONDRIAL DNA; TRANSPOSITION; AMPLIFICATION; D(CA)-RICH REPEATS; PSEUDOGENES ID HOMOLOGOUS RECOMBINATION; NUCLEOTIDE-SEQUENCE; NEUROSPORA-CRASSA; RIBOSOMAL-RNA; EVOLUTION; GENE; ORGANIZATION; CHLOROPLAST; TRANSCRIPTION; PERSPECTIVES AB The mitochondrial DNA of plant and animal cells is a transcriptionally active genome that traces its origins to a symbiotic infection of eucaryotic cells by bacterial progenitors. As prescribed by the Serial Endosymbiosis Theory, symbiotic organelles have gradually transferred their genes to the eucaryotic genome, producing a functional interaction of nuclear and mitochondrial chondrial genes in organelle function. We report there a recent remarkable transposition of 7.9 kb of a typically 17.0-kb mitochondrial genome to a specific nuclear chromosomal position in the domestic cat. The integrated segment has subsequently become amplified 38-76 times and now occurs as a tandem repeat macrosatellite with multiple-length alleles resolved by pulse-field gel electrophoresis (PFGE) segregating in cat populations. Sequence determination of the nuclear mitochondrial DNA segment, Numt, revealed a d(CA)-rich 8-bp motif [ACACACGT] repeated imperfectly five times at the deletion junction that is a likely target for recombination. The extent and pattern of sequence divergence of Numt genes from the cytoplasmic mtDNA homologues plus the occurrence of Numt in other species of the family Felidae allowed an estimate for the origins of Numt at 1.8-2.0 million years ago in an ancestor of four modern species in the genus Felis. Numt genes do not function in cats; rather, the locus combines properties of nuclear minisatellites and pseudogenes. These observations provide an empirical glimpse of historic genomic events that may parallel the accommodation of organelles in eucaryotes. C1 GEORGE MASON UNIV,DEPT BIOL,FAIRFAX,VA 22030. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP LOPEZ, JV (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. RI Lopez, Jose/F-8809-2011 OI Lopez, Jose/0000-0002-1637-4125 NR 78 TC 316 Z9 332 U1 3 U2 30 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD AUG PY 1994 VL 39 IS 2 BP 174 EP 190 PG 17 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA NX168 UT WOS:A1994NX16800008 PM 7932781 ER PT J AU HOELZEL, AR LOPEZ, JV DOVER, GA OBRIEN, SJ AF HOELZEL, AR LOPEZ, JV DOVER, GA OBRIEN, SJ TI RAPID EVOLUTION OF A HETEROPLASMIC REPETITIVE SEQUENCE IN THE MITOCHONDRIAL-DNA CONTROL REGION OF CARNIVORES SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE DNA; DNA SLIPPAGE; REPETITIVE; DNA; CARNIVORES ID D-LOOP REGION; NONCODING REGION; REPEATS; RECOMBINATION; REPLICATION; METHYLATION; GENERATION; POLYMERASE; PHYLOGENY; LENGTH AB We describe a repetitive DNA region at the 3' end of the mitochondrial DNA (mtDNA) control region and compare it in 21 carnivore species representing eight carnivore families. The sequence and organization of the repetitive motifs can differ extensively between arrays; however, all motifs appear to be derived from the core motif ''ACGT.'' Sequence data and Southern blot analysis demonstrate extensive heteroplasmy. The general form of the array is similar between heteroplasmic variants within an individual and between individuals within a species (varying primarily in the length of the array, though two clones from the northern elephant seal are exceptional). Within certain families, notably ursids, the array structure is also similar between species. Similarity between species was not apparent in other carnivore families, such as the mustelids, suggesting rapid changes in the organization and sequence of some arrays. The pattern of change seen within and between species suggests that a dominant mechanism involved in the evolution of these arrays is DNA slippage. A comparative analysis shows that the motifs that are being reiterated or deleted vary within and between arrays, suggesting a varying rate of DNA turnover. We discuss the evolutionary implications of the observed patterns of variation and extreme levels of heteroplasmy. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV LEICESTER,DEPT GENET,LEICESTER LE1 7RH,ENGLAND. RP HOELZEL, AR (reprint author), NCI,VIRAL CARCINOGENESIS LAB,BLD 560,FREDERICK,MD 21702, USA. RI Lopez, Jose/F-8809-2011 OI Lopez, Jose/0000-0002-1637-4125 NR 47 TC 97 Z9 102 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD AUG PY 1994 VL 39 IS 2 BP 191 EP 199 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA NX168 UT WOS:A1994NX16800009 PM 7932782 ER PT J AU WASHIZAKI, K SMITH, QR RAPOPORT, SI PURDON, AD AF WASHIZAKI, K SMITH, QR RAPOPORT, SI PURDON, AD TI BRAIN ARACHIDONIC-ACID INCORPORATION AND PRECURSOR POOL SPECIFIC ACTIVITY DURING INTRAVENOUS-INFUSION OF UNESTERIFIED [H-3] ARACHIDONATE IN THE ANESTHETIZED RAT SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ARACHIDONATE; LIPID METABOLISM; PHOSPHOLIPID; ACYL-COA; BRAIN; RAT ID FREE FATTY-ACIDS; ACYL-COA ESTERS; CHOLINERGIC STIMULATION; PALMITATE INCORPORATION; SUBCELLULAR-FRACTIONS; UNANESTHETIZED RATS; PHOSPHATIDIC-ACID; PROTEIN-SYNTHESIS; BINDING-PROTEINS; METABOLISM AB Brain fatty acid incorporation into phospholipids can be measured in vivo following intravenous injection of fatty acid tracer. However, to calculate a cerebral incorporation rate, knowledge is required of tracer specific activity in the final brain precursor pool. To determine this for one tracer, unesterified [H-3]arachidonate was infused intravenously in pentobarbital-anesthetized rats to maintain constant plasma specific activity for 1-10 min. At the end of infusion, animals were killed by microwave irradiation and analyzed for tracer specific activity and concentration in brain phospholipid, neutral lipid, and lipid precursor, i.e., unesterified arachidonate and arachidonoyl-CoA, pools. Tracer specific activity in brain unesterified arachidonate and arachidonoyl-CoA rose quickly (t(1/2)<1 min) to steady-state values that averaged <5% of plasma specific activity. Incorporation was rapid, as >85% of brain tracer was present in phospholipids at 1 min of infusion. The results demonstrate that unesterified arachidonate is rapidly taken up and incorporated in brain but that brain phospholipid precursor pools fail to equilibrate with plasma in short experiments. Low brain precursor specific activity may result from (a) dilution of label with unlabeled arachidonate from alternate sources or (b) precursor pool compartmentalization. The results suggest that arachidonate turnover in brain phospholipids is more rapid than previously assumed. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 47 TC 90 Z9 91 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1994 VL 63 IS 2 BP 727 EP 736 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NZ017 UT WOS:A1994NZ01700043 PM 8035197 ER PT J AU REINHARDT, RR CHIN, E ZHANG, B ROTH, RA BONDY, CA AF REINHARDT, RR CHIN, E ZHANG, B ROTH, RA BONDY, CA TI SELECTIVE COEXPRESSION OF INSULIN RECEPTOR-RELATED RECEPTOR (IRR) AND TRK IN NGF-SENSITIVE NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NEURAL CREST; TYROSINE KINASE; BASAL FOREBRAIN; SENSORY NEURON; NEUROTROPHIN; EMBRYONIC DEVELOPMENT ID GROWTH FACTOR-I; TYROSINE PROTEIN-KINASE; GENE-EXPRESSION; SENSORY NEURONS; MESSENGER-RNA; IGF-I; NEUROTROPHIN-3; PROTOONCOGENE; SPECIFICITY; ONCOGENE AB The insulin receptor-related receptor (IRR) has recently been identified as a member of the insulin receptor tyrosine kinase family; however, its endogenous ligand and biological function are still unknown. In contrast to the very widespread pattern of expression of the homologous insulin and IGF-I receptors, IRR demonstrates a very restricted cellular distribution. Using in situ hybridization and immunohistochemistry, we now show that the expression of this receptor is selectively concentrated in a subset of neurons where its appearance is closely associated with that of the NGF receptor TRK. IRR and TRK demonstrate synchronized patterns of coexpression in neural crest-derived sensory and sympathetic neurons and in non-neural crest basal forebrain and striatal neurons. Both appear early in the embryonic development of dorsal root and trigeminal neurons and somewhat later, near the time of birth, in sympathetic neurons. Expression of both IRR and TRK appears perinatally in basal forebrain neurons, reaching maximal levels about postnatal day 20. This association is highly selective, since TRK mRNA is not detected anywhere in the developing nervous system in the absence of coordinate IRR expression, and the same is true for inn expression with respect to TRK. In the adult rat, the majority of TRK-positive sensory neurons still express IRR mRNA, and coexpression in sympathetic and forebrain neurons continues without evidence of diminution. These findings are consistent with a functional linkage of the IRR and TRK receptors in NGF-sensitive neurons. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. STANFORD UNIV, DEPT PHARMACOL, STANFORD, CA 94305 USA. FU NIDDK NIH HHS [DK 456521] NR 26 TC 35 Z9 35 U1 0 U2 0 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 AUG PY 1994 VL 14 IS 8 BP 4674 EP 4683 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PA953 UT WOS:A1994PA95300007 PM 8046442 ER PT J AU BRADY, LS LYNN, AB HERKENHAM, M GOTTESFELD, Z AF BRADY, LS LYNN, AB HERKENHAM, M GOTTESFELD, Z TI SYSTEMIC INTERLEUKIN-1 INDUCES EARLY AND LATE PATTERNS OF C-FOS MESSENGER-RNA EXPRESSION IN BRAIN SO JOURNAL OF NEUROSCIENCE LA English DT Article DE INTERLEUKIN-1; C-FOS; PARAVENTRICULAR NUCLEUS; HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS; LIMBIC SYSTEM; AREA POSTREMA; NUCLEUS OF THE SOLITARY TRACT ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL AMYGDALOID NUCLEUS; PLASMA-CORTICOSTERONE RESPONSES; RECEPTOR MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; STRIA TERMINALIS; SOLITARY TRACT; BED NUCLEUS AB This study was designed to examine the mechanisms by which systemic interleukin-1 affects neuroendocrine systems in the brain. Intraperitoneal injections of interleukin-1 beta (1.25 mu g/rat) were administered to rats. One or three hours after injection, the expression levels of the immediate-early gene c-fos and of genes for several neuropeptides, receptors, and enzymes were examined by in situ hybridization histochemistry. In the brainstem at 1 hr, c-fos mRNA was elevated in the area postrema and nucleus of the solitary tract, but not in the locus coeruleus. At 3 hr, the c-fos mRNA levels had increased further in the nucleus of the solitary tract. Rostrally, elevations in c-fos mRNA levels were found in the hypothalamic and thalamic paraventricular nuclei, central nucleus of amygdala, bed nucleus of the stria terminalis, and medial preoptic area, peaking at 1 hr and diminishing at 3 hr. In addition, at 3 hr a new pattern of c-fos activity emerged-the arcuate nucleus and cells at the external margins throughout the brain now expressed c-fos mRNA. Corticotropin-releasing hormone mRNA levels were doubled in the paraventricular nucleus at 1 and 3 hr, concomitant with elevations in plasma adrenocorticotrophic hormone (ACTH) and corticosterone. Tyrosine hydroxylase mRNA levels in the brainstem did not change. The c-fos mRNA induction patterns reveal a temporally dynamic response to interleukin-1 administration. We propose that the early set of structures responding to interleukin-1 initiates the neuroendocrine response to cytokines. Coactivation of the area postrema and nucleus of the solitary tract may reflect entry into the brain and neural transduction of the peripheral signal. The late set-including the nucleus of the solitary tract, arcuate nucleus, and the brain's edge-may reflect cellular activation along the diffusion routes traveled by interleukin-1 or a bioactive transduction product, because the pattern of edge labeling is similar to the autoradiographic pattern of flow of radiolabeled tracer substances in the cerebrospinal fluid. The late c-fos mRNA response to interleukin-1, therefore, may represent a demonstration of information transfer in the para-synaptic mode, also known as volume transmission. C1 UNIV TEXAS,SCH MED,DEPT NEUROBIOL & ANAT,HOUSTON,TX 77225. RP BRADY, LS (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 69 TC 143 Z9 145 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG PY 1994 VL 14 IS 8 BP 4951 EP 4964 PG 14 WC Neurosciences SC Neurosciences & Neurology GA PA953 UT WOS:A1994PA95300033 PM 7913957 ER PT J AU RAM, Z WALBRIDGE, S SHAWKER, T CULVER, KW BLAESE, RM OLDFIELD, EH AF RAM, Z WALBRIDGE, S SHAWKER, T CULVER, KW BLAESE, RM OLDFIELD, EH TI THE EFFECT OF THYMIDINE KINASE TRANSDUCTION AND GANCICLOVIR THERAPY ON TUMOR VASCULATURE AND GROWTH OF 9L GLIOMAS IN RATS SO JOURNAL OF NEUROSURGERY LA English DT Article DE GENE THERAPY; BRAIN NEOPLASM; THYMIDINE KINASE; GANCICLOVIR; TUMOR VASCULATURE; BYSTANDER EFFECT; RAT ID MEDIATED GENE-TRANSFER; BRAIN-TUMORS; CELLS AB Eradication of malignant brain tumors by in situ intratumoral, retrovirally mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes the tumor cells to ganciclovir, has recently been demonstrated in animal models. The observation that tumors studied in vitro and in animals can be completely eliminated despite only partial transduction of the tumor suggests a bystander mechanism that affects nontransduced tumor cells. Such a bystander effect is not completely understood and may represent a combination of several factors that lead to tumor eradication. Endothelial cells of the tumor blood vessels were shown to occasionally integrate the retroviral vector and thus become sensitized to ganciclovir. In the presence of vector-producer cells, which continuously release infectious viral particles, diffuse multifocal hemorrhages occurred during ganciclovir administration. When the tumor was composed of cells that had been transduced with the thymidine kinase gene before inoculation, no infectious viral particles were present within the tumor, no transduction of endothelial cells occurred, and no hemorrhages were observed during ganciclovir therapy. These observations suggest that tumor regression may be due, in part, to destruction of in vivo HSVtk-transduced endothelial cells after exposure to ganciclovir, resulting in tumor ischemia as one possible bystander mechanism. The authors investigated this hypothesis using the subcutaneous 9L gliosarcoma tumor model in Fischer rats. The tumors were evaluated with Doppler color-flow and ultrasound imaging during the various phases of the study. Twenty rats received intratumoral injections of HSVtk retroviral vector-producer cells (6 x 10(7) cells/ml) 21 days after bilateral flank tumor inoculation. Ten rats were subsequently treated with intraperitoneal ganciclovir (15 mg/kg/ml twice a day) for 14 days starting on Day 7 after producer cell injection; 10 control rats received intraperitoneal saline injections (1 ml twice a day) instead of ganciclovir. Ultrasound and flow images were obtained before cell injection, before and during ganciclovir or saline administration, and after cessation of treatment. The number, location, and ultrasonographic appearance of tumor vessels and the tumor volumes were recorded. The number of blood vessels in the tumors increased over time in both groups before treatment. Intratumoral cell injection without ganciclovir administration did not influence tumor growth or intratumoral vasculature. However, tumor vasculature decreased after initiation of ganciclovir therapy in the HSVtk-transduced tumors (p < 0.05). Early patchy or diffuse necrotic changes associated with ultrasonographic evidence of scattered intratumoral hemorrhage occurred in tumors treated with ganciclovir. Reduction of the tumor blood supply may be an important feature of HSVtk transduction-mediated tumor regression and may, at least partially, account for the degree of tumor destruction that occurs despite the lack of transduction of all tumor cells. C1 NCI,DEPT RADIOL,BETHESDA,MD 20892. NCI,CTR CLIN,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RP RAM, Z (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10-5D37,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 145 Z9 152 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 AUG PY 1994 VL 81 IS 2 BP 256 EP 260 DI 10.3171/jns.1994.81.2.0256 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NY086 UT WOS:A1994NY08600016 PM 8027810 ER PT J AU POTTERN, LM ZAHM, SH SIEBER, SS SCHNEIDER, IJ LAROSA, JH BROWN, DP COLLMAN, GW FINGERHUT, MA WATERS, MA AF POTTERN, LM ZAHM, SH SIEBER, SS SCHNEIDER, IJ LAROSA, JH BROWN, DP COLLMAN, GW FINGERHUT, MA WATERS, MA TI OCCUPATIONAL-CANCER AMONG WOMEN - A CONFERENCE OVERVIEW SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material C1 NIH,OFF RES WOMENS HLTH,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. NIOSH,CINCINNATI,OH 45226. RP POTTERN, LM (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Waters, Martha/B-7441-2011; Zahm, Shelia/B-5025-2015 NR 31 TC 12 Z9 12 U1 0 U2 0 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 AUG PY 1994 VL 36 IS 8 BP 809 EP 813 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500001 PM 7807258 ER PT J AU DEVESA, SS GRAUMAN, DJ BLOT, WJ AF DEVESA, SS GRAUMAN, DJ BLOT, WJ TI RECENT CANCER PATTERNS AMONG MEN AND WOMEN IN THE UNITED-STATES - CLUES FOR OCCUPATIONAL RESEARCH SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID BLADDER-CANCER; WHITE WOMEN; RISKS AB Investigation of cancer rates-including trends over time geographic variations, and differences by race, gender, and age-may identify patterns suggesting environmental exposures of potential occupational origin. National mortality data spanning the 40-year period from 1950 to 1989 were used to assess the patterns of several cancers for which occupational components have been identified among men, including cancers of the lung and bladder, non-Hodgkin's lymphoma, and leukemia, and for cancers of particular concern to women, such as breast and ovarian cancer, but for which occupational factors have not been well characterized. Newly available preliminary data show substantial geographic variation in cancer mortality rates at the county level during the 1970s and 1980s. Future analyses of the patterns, correlations with industrial indicators, and analytic studies should be fruitful in identifying occupational and other risk factors for cancers among women. RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 17 TC 6 Z9 6 U1 0 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 AUG PY 1994 VL 36 IS 8 BP 832 EP 841 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500004 PM 7807262 ER PT J AU ZAHM, SH POTTERN, LM LEWIS, DR WARD, MH WHITE, DW AF ZAHM, SH POTTERN, LM LEWIS, DR WARD, MH WHITE, DW TI INCLUSION OF WOMEN AND MINORITIES IN OCCUPATIONAL-CANCER EPIDEMIOLOGIC RESEARCH SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID BREAST-CANCER; RESIDUES; DEATH; RISK AB A survey of published epidemiologic studies from eight journals during 1971 to 1990 was conducted to assess the proportion and characteristics of occupational cancer studies that have included women and minorities. A total of 1233 reports included 562 (46%) with subjects limited to white men. The remaining 671 (54%) had subjects from other race-gender groups. Thirty-five percent included white women, but only 14% presented any analyses of white women specifically and only 7% presented more than Jive risk estimates. The proportions with analyses of nonwhite women (any = 2%, detailed = 1%) or men (any = 7%, detailed = 3%) were also small. Studies with detailed analyses of women and minorities tended to use weaker methodologies (ie, proportionate mortality or cross-sectional design) than the studies of white men and were less able to provide convincing data on the occupational cancer risks of women and minorities. C1 NOVA RES CO,BETHESDA,MD. RP ZAHM, SH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 16 TC 61 Z9 63 U1 0 U2 2 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 AUG PY 1994 VL 36 IS 8 BP 842 EP 847 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500005 PM 7807263 ER PT J AU POTTERN, LM AF POTTERN, LM TI WOMEN IN THE WORKPLACE - DISCUSSION SESSION-I SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Discussion RP POTTERN, LM (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,6130 EXECUT BLVD,BETHESDA,MD 20892, 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 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 1994 VL 36 IS 8 BP 848 EP 848 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500006 ER PT J AU GRIESEMER, RA EUSTIS, SL AF GRIESEMER, RA EUSTIS, SL TI GENDER DIFFERENCES IN ANIMAL BIOASSAYS FOR CARCINOGENICITY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID BODY-WEIGHT; F344/N RATS; SURVIVAL AB Animal bioassays for carcinogenicity are essential components of occupational health studies. Animal data that have been collected under controlled experimental conditions provide definitive information about the carcinogenic activities of individual substances ol defined mixtures and their relative potencies in the test species. Such information serves as a frame of reference for clinical and epidemiologic studies, pointing to potential adverse health effects and to the types of substances that might produce them. This article alerts the occupational and environmental health communities to 20 substances that produced breast tumors, 13 substances that produced uterine tumors, and 8 substances that produced ovarian tumors in long-term National Toxicology Program animal studies. Each of the substances also produced neoplasms at other body sites. Follow-up studies of molecular measures of exposure and response in people and in animals will reduce the uncertainties of transspecies extrapolations. C1 SMITHKLINE BEECHAM PHARMACEUT,KING OF PRUSSIA,PA 19406. RP GRIESEMER, RA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 7 Z9 8 U1 0 U2 0 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 AUG PY 1994 VL 36 IS 8 BP 855 EP 859 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500008 PM 7807265 ER PT J AU WARD, EM RUDER, AM SURUDA, A SMITH, AB HALPERIN, W FESSLER, CA ZAHM, SH AF WARD, EM RUDER, AM SURUDA, A SMITH, AB HALPERIN, W FESSLER, CA ZAHM, SH TI CANCER MORTALITY PATTERNS AMONG FEMALE AND MALE WORKERS EMPLOYED IN A CABLE MANUFACTURING PLANT DURING WORLD-WAR-II SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID TABLE ANALYSIS SYSTEM; POLYCHLORINATED-BIPHENYLS; DIOXIN EXPOSURE; UNITED-STATES; BREAST-CANCER; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; INDUCTION; RESIDUES; LIVER; RATS AB A cohort mortality study was conducted among 9028 (3042 women, 5986 men) workers potentially exposed to chlorinated naphthalenes (chloracnegens structurally similar to dioxins) and asbestos in the manufacture of Navy cable during World War II. Based on mortality through December 31, 1985, standardized mortality ratios (SMRs) for all cancers was 1.03 in women (95% confidence interval [CI] = 0.90 to 1.17) and 1.18 in men (95% CI = 1.10 to 1.26). There were no significant elevations in causes of death hypothesized a priori to be associated with chlorinated naphthalene exposure (malignant neoplasms [MN] of connective tissue, liver, and lymphatic and hematopoietic organs). An excess of MN of the connective tissue was suggested for workers with over 1 year of exposure and 25 years of latency (SMR = 3.54, 95% CI = 0.97 to 9.07). Among cancer sites not hypothesized to be related a priori, three showed concordant excesses among both genders (MN of stomach; rectum; and trachea, bronchus, and lung). No significant elevations occurred in hormonally related cancers among women. Cancer mortality among 460 individuals with chloracne (431 men, 29 women) was similar to that of the entire cohort, although the chloracne subcohort showed significant excesses in two rare causes of death (MN of esophagus, SMR = 3.26, ''benign and unspecified neoplasms,'' SMR = 4.93). Use of county referent rates decreased SMRs for stomach, rectal, and buccal cavity cancer suggesting a role for nonoccupational risk factors. If is difficult to draw conclusions about carcinogenicity of chlorinated naphthalenes because of study limitations, most importantly, concomitant asbestos exposure and the relatively short duration of exposure to chlorinated naphthalenes among most of the cohort. C1 NCI,BETHESDA,MD 20892. RP WARD, EM (reprint author), NIOSH,MAIL STOP R-13,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. RI Ruder, Avima/I-4155-2012; Zahm, Shelia/B-5025-2015 OI Ruder, Avima/0000-0003-0419-6664; NR 28 TC 16 Z9 16 U1 1 U2 2 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 AUG PY 1994 VL 36 IS 8 BP 860 EP 866 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500009 PM 7807266 ER PT J AU RUDER, AM WARD, EM BROWN, DP AF RUDER, AM WARD, EM BROWN, DP TI CANCER MORTALITY IN FEMALE AND MALE DRY-CLEANING WORKERS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID TABLE ANALYSIS SYSTEM; BLADDER-CANCER; RISK-FACTORS; NEW-JERSEY; LAUNDRY; COHORT; PERCHLOROETHYLENE; PRODUCTS; CLEANERS; DEATH AB A cohort study of dry-cleaning workers (1109 women, 592 men) in the mid-1980s revealed significant excess bladder cancer mortality. This article updates vital status through 1990. Significant excesses were seen for bladder cancer (nine deaths, standardized mortality ratio [SMR] = 2.54, 95% confidence interval [CI] = 1.16-4.82), esophageal cancer (10 deaths, SMR = 2.14, 95% CI = 1.02-3.94), and intestinal cancer (26 deaths, SMR = 1.56, 95% CI = 1.02-2.29). In a subcohort exposed only to perchloroethylene (PCE), those with 5 or more years of employment and 20 or more years since first exposure had a significant increased risk of esophageal cancer (four deaths, SMR = 7.17, 95% CI = 1.92-19.82). Women had significant excess esophageal cancer (five deaths, SMR = 3.24, 95% CI = 1.05-7.58) and elevated SMRs for intestinal, pancreatic, and bladder cancer mortality. This study confirms the esophageal cancer risk among dry-cleaning workers seen in another study and suggests an association with PCE. It further documents the risks for intestinal, pancreatic, and bladder cancers in this industry. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP RUDER, AM (reprint author), NIOSH,MAILSTOP R-16,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. RI Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 25 TC 61 Z9 62 U1 1 U2 3 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 AUG PY 1994 VL 36 IS 8 BP 867 EP 874 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500010 PM 7807267 ER PT J AU LI, GL LINET, MS HAYES, RB YIN, SN DOSEMECI, M WANG, YZ CHOW, WH JIANG, ZL WACHOLDER, S ZHANG, WU DAI, TR CHAO, XJ ZHANG, XC YE, PZ KOU, QR MENG, JF ZHO, JS LIN, XF DING, CY WU, C BLOT, WJ AF LI, GL LINET, MS HAYES, RB YIN, SN DOSEMECI, M WANG, YZ CHOW, WH JIANG, ZL WACHOLDER, S ZHANG, WU DAI, TR CHAO, XJ ZHANG, XC YE, PZ KOU, QR MENG, JF ZHO, JS LIN, XF DING, CY WU, C BLOT, WJ TI GENDER DIFFERENCES IN HEMATOPOIETIC AND LYMPHOPROLIFERATIVE DISORDERS AND OTHER CANCER RISKS BY MAJOR OCCUPATIONAL GROUP AMONG WORKERS EXPOSED TO BENZENE IN CHINA SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CAUSE-SPECIFIC MORTALITY; INDUSTRY WIDE MORTALITY; RUBBER WORKERS; CHEMICAL WORKERS; LEUKEMIA; COHORT; PAINTERS; EXPERIENCE; EMPLOYEES; EXPOSURES AB Gender differences in risk for leukemia and other selected and combined disease categories were examined by major occupational category for 74,828 benzene-exposed workers compared to 35,805 unexposed workers from 12 cities in China, No significant differences in the relative risks for total mortality and cancer mortality were found between female and male benzene-exposed workers, although risks tended to be somewhat higher among male than among female employees. Both female and male workers in several occupational categories had notably increased risks for all hematopoietic and lymphoproliferative (HLP) malignant and nonmalignant disorders combined and for total leukemia. Variation in risk for HLP disorders by occupational category was observed in both genders, with highest risks for male and female chemical manufacturing workers, female nonproduction employees, and male printers. However, the numbers of leukemia and other HLP malignancies in each category were small. The findings suggest that both female and male benzene-exposed workers in several occupational categories experience excess leukemia and other HLP disorders with relatively minor gender differences. Although this population is one of the largest cohorts of benzene-exposed workers studied to date, evaluation of the observed variation in risk for HLP neoplasms among the occupational groups for workers of each gender is limited by the small numbers of these relatively rare malignancies. C1 STN PUBL HLTH & PREVENT INFECT, SHANGHAI, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHENGDU, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHONGQING, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, TIANJIN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SICHUAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HENAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HEILONGJIANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SHENYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JIANGXI, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, NANCHANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, GUANGZHO, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JINZHOU, PEOPLES R CHINA. CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING 100050, PEOPLES R CHINA. RP LI, GL (reprint author), NCI, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, EXECUT PLAZA N 415, BETHESDA, MD 20892 USA. NR 55 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 1994 VL 36 IS 8 BP 875 EP 881 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500011 PM 7807268 ER PT J AU BROWN, DP DEMENT, JM OKUN, A AF BROWN, DP DEMENT, JM OKUN, A TI MORTALITY PATTERNS AMONG FEMALE AND MALE CHRYSOTILE ASBESTOS TEXTILE WORKERS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID DUST EXPOSURE; CARCINOGENICITY AB This study updates a retrospective cohort mortality analysis of workers from a South Carolina textile plant where chrysotile asbestos was the primary exposure. The update adds 15 years of observation to the original study, adds analyses of white women and black men, and allows comparison of mortality risks between race/gender groups. The total cohort includes 3,022 workers: 1,229 white women (363 deaths), 1,247 white men (607 deaths), and 546 black men (289 deaths). Statistically significant risks for lung cancer were observed among white women (standardized mortality ratio [SMR] = 2.07; 90% confidence interval [CI] = 1.55-2.71) and white men (SMR = 2.24; 90% CI = 1.83-2.72); both of these groups exhibited positive exposure-response trends. Although the lung cancer risk among black men was lower than expected (SMR = 0.70; 90% CI = 0.42-1.08), a statistically significant increase was observed at high levels of exposure. Statistically significant excess risks for pneumoconiosis and other respiratory diseases were observed for all race/gender groups. Despite the relatively high percentage of white women lost to follow-up and missing death certificates, both of which allow underestimation of the true relative risk, statistically significant excess risks were observed for lung cancer and pneumoconiosis among this group. C1 DUKE UNIV,DEPT OCCUPAT HLTH,DURHAM,NC. NIOSH,IND WIDE STUDIES BRANCH,CINCINNATI,OH 45226. RP BROWN, DP (reprint author), NIEHS,OFF DIS PREVENT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 27 Z9 28 U1 1 U2 4 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 AUG PY 1994 VL 36 IS 8 BP 882 EP 888 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500012 PM 7807269 ER PT J AU POTTERN, LM AF POTTERN, LM TI GENDER DIFFERENCES RELATED TO CANCER RISKS - DISCUSSION SECTION-II SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Discussion RP POTTERN, LM (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,6130 EXECUT BLVD,BETHESDA,MD 20892, 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 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 1994 VL 36 IS 8 BP 906 EP 906 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500017 ER PT J AU STEWART, PA BLAIR, A AF STEWART, PA BLAIR, A TI WOMEN IN THE FORMALDEHYDE INDUSTRY - THEIR EXPOSURES AND THEIR JOBS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI AB Several studies have examined disease risks for women separately from risks for men, but few have examined exposure differences. This report used data from an epidemiological study of formaldehyde workers to compare formaldehyde exposures between men and women. Exposures were estimated from historical monitoring results, walk-through workplace surveys, interviews with long-term workers, and reviews of historical records. The mean of the exposures in the first job, the last job, and the highest exposed job were calculated by gender. Differences were found when all subjects were included in the analysis (men having higher exposures, on average, than women), bur when nonexposed subjects were removed (40% of women, 6% of men), differences were minor. There was a substantial difference in the estimated peak exposure between men and women that decreased, but remained, when only exposed subjects were included Evaluation of exposures in 1940 to 1945, 1965, and 1979 found that women had a higher average exposure than men in 1940 to 1945, but this pattern was reversed in 1965. By 1979, the average difference between the two genders had disappeared. A comparison of cumulative exposure found that exposed women had half the total exposure of exposed men. More men than women were exposed to other chemicals. Women tended to predominate in clerical, laboratory, assembly, finishing, inspecting, packing, and shipping jobs. RP STEWART, PA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N 418,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 7 U1 0 U2 2 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 AUG PY 1994 VL 36 IS 8 BP 918 EP 923 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500020 PM 7807276 ER PT J AU HARTGE, P STEWART, P AF HARTGE, P STEWART, P TI OCCUPATION AND OVARIAN-CANCER - A CASE-CONTROL STUDY IN THE WASHINGTON, DC, METROPOLITAN-AREA, 1978-1981 SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health: Occupation and Cancer CY NOV 01-02, 1993 CL BALTIMORE, MD SP NIEHS, NIH, OFF RES WOMENS HLTH, NIOSH, CTR DIS CONTROL & PREVENT, NCI ID STATES CASE-CONTROL; COLLABORATIVE ANALYSIS; WHITE WOMEN; RISK AB Ovarian cancer risk factors may be genetic, reproductive, or hormonal in nature. Occupational exposure to talc and other carcinogenic substances has not been studied in relation to ovarian cancer risk. We therefore examined the job histories of 296 women aged 20 to 79 who were diagnosed with epithelial ovarian cancer in the Washington, DC area in 1978 to 1981, comparing them to 343 hospital controls, matched for age and race. A blind exposure assessment, evaluating each job/industry combination for potential exposure to talc, ionizing radiation, polycyclic aromatic hydrocarbons, and solvents was conducted by an industrial hygienist blind to case-control status. Women exposed to talc had a relative risk of ovarian cancer below the null, but the confidence interval was wide and there was no evidence of a trend. Women exposed to polycyclic aromatic hydrocarbons had an elevated relative risk, also with a wide confidence interval and no evidence of a trend with duration. RP HARTGE, P (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 13 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 AUG PY 1994 VL 36 IS 8 BP 924 EP 927 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500021 PM 7807277 ER PT J AU POTTERN, LM AF POTTERN, LM TI METHODOLOGIC ISSUES IN OCCUPATIONAL STUDIES - DISCUSSION SESSION-III SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Discussion RP POTTERN, LM (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,6130 EXECUT BLVD,BETHESDA,MD 20892, 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 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 1994 VL 36 IS 8 BP 928 EP 928 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ115 UT WOS:A1994PJ11500022 ER PT J AU FAIMAN, CP VIU, E SKOLNICK, P TRULLAS, R AF FAIMAN, CP VIU, E SKOLNICK, P TRULLAS, R TI DIFFERENTIAL-EFFECTS OF COMPOUNDS THAT ACT AT STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS IN A PUNISHMENT PROCEDURE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; NMDA RECEPTOR; 1-AMINOCYCLOPROPANECARBOXYLIC ACID; EXHIBIT ANTIDEPRESSANT; FUNCTIONAL ANTAGONISTS; SELECTIVE IMPAIRMENT; MODULATORY SITE; XENOPUS-OOCYTES; ANIMAL-MODELS AB The anxiolytic and memory-impairing effects of compounds that act at strychnine-insensitive (SI) glycine receptors were examined and compared with those of a competitive N-methyl-D-aspartate antagonist, 2-amino-7-phosphonoheptanoic acid (AP7); a use-dependent channel blocker, dizocilpine; and a benzodiazepine agonist, diazepam (DZP). Mice were trained to avoid a dark compartment and their latencies to step through were measured either within 1 hr after training in the presence of the drug (to assess the anxiolytic effects) or 24 hr after pre- or post-training treatment (to assess the effects on learning and memory). Post-training administration of the glycinergic compounds 1-aminocyclopropanecarboxylic acid, 7-chlorokynurenic acid and D-cycloserine reduced step-through latencies when testing was performed 30 min after drug treatment and within 1 h after training. Latencies were unaltered by these glycinergic compounds when testing was performed 24 hr later. Similar results were obtained with AP7 and DZP. In contrast, an amnesic dose of pentylenetetrazole reduced latencies both within 1 and 24 hr after training. Pretreatment with glycine abolished the reduction in latencies observed with SI glycine receptor ligands 1 hr after training but did not antagonize the reduction produced by AP7. Pretraining administration of SI glycine receptor ligands did not alter step-through latencies measured 24 hr later. In contrast, under these same conditions, AP7, dizocilpine and DZP produced a significant reduction in latencies. These results demonstrate that compounds that act at SI glycine receptors do not impair learning and memory at doses that are anxiolytic in a single-trial punishment paradigm. C1 CSIC,CID,NEUROBIOL UNIT,E-08034 BARCELONA,SPAIN. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RI Trullas, Ramon/D-2197-2016 OI Trullas, Ramon/0000-0001-7951-9881 NR 48 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1994 VL 270 IS 2 BP 528 EP 533 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PD455 UT WOS:A1994PD45500015 PM 8071846 ER PT J AU RUMPEL, C HARRIS, TB AF RUMPEL, C HARRIS, TB TI THE INFLUENCE OF WEIGHT ON ADOLESCENT SELF-ESTEEM SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE ADOLESCENT; SELF-ESTEEM; BODY WEIGHT; LOCUS OF CONTROL ID CHILDHOOD OBESITY; CHILDREN; OVERWEIGHT; ADJUSTMENT; FATNESS; SCORES; GIRLS; LOCUS AB Overweight children have traditionally been thought to have lower self-esteem than other children. Prospective data from the California Child Health and Development Studies were used to test this hypothesis by examination of the relationship between body mass index, self-esteem and locus of control while controlling for demographic and baseline psychosocial traits. Principle components and confirmatory factor analysis were used to derive latent constructs for self-esteem, locus of control and other psychosocial factors. A covariance structure model was developed using the results of the confirmatory factor analysis. In this model, adolescent self-esteem, locus of control and body mass index were not related. These findings from prospective data in a non-clinical population suggest that although some subgroups of obese children may be vulnerable for decreased self-esteem, this does not appear to be a significant problem in the general population. C1 NIA,BETHESDA,MD 20816. UNIV S CAROLINA,SCH MED,DIV PREVENT MED,COLUMBIA,SC 29208. UNIV S CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,COLUMBIA,SC 29208. RP RUMPEL, C (reprint author), NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,ROOM 1000,6525 BELCREST RD,HYATTSVILLE,MD 20782, USA. NR 39 TC 13 Z9 14 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 AUG PY 1994 VL 38 IS 6 BP 547 EP 556 DI 10.1016/0022-3999(94)90052-3 PG 10 WC Psychiatry SC Psychiatry GA PE091 UT WOS:A1994PE09100008 PM 7990063 ER PT J AU RALL, WF WOOD, MJ AF RALL, WF WOOD, MJ TI HIGH IN-VITRO AND IN-VIVO SURVIVAL OF DAY-3 MOUSE EMBRYOS VITRIFIED OR FROZEN IN A NONTOXIC SOLUTION OF GLYCEROL AND ALBUMIN SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article ID VITRIFICATION SOLUTION; MAMMALIAN EMBRYOS; LIQUID-NITROGEN; PLASTIC STRAWS; WARMING RATE; CRYOPRESERVATION; STAGE; CRYOPROTECTANT; -196-DEGREES-C; PRESERVATION AB A vitrification solution consisting of 6.5 mol glycerol l(-1) and 6% (w/v) BSA in a modified Dulbecco's PBS (designated solution VS3a) was examined for the cryopreservation of 8-12-cell mouse embryos. Solution VS3a vitrified when cooled to - 196 degrees C at rates of 10-2500 degrees C min(-1) and vitrified suspensions did not crystallize when warmed at 200 or 2000 degrees C min(-1). However, slow cooling at 5 degrees C min(-1) or slow warming at 20 degrees C min(-1) resulted in visible crystallization of solution VS3a. Embryos were equilibrated in solution VS3a in three steps at room temperature and placed into a 0.25 ml plastic straw in a way that permitted in-straw dilution with 1 mol sucrose l(-1). Embryos equilibrated in solution VS3a and diluted immediately exhibited high rates of development in vitro to blastocysts (> 90%) if the total time of exposure to 100% solution VS3a did not exceed 5 min. Embryos exhibited high rates of development in vitro (75-97%) when equilibrated in 100% solution VS3a for 1 min and then cryopreserved using all combinations of three rates of cooling (5200 or 2500 degrees C min(-1)) and three rates of warming (20 200 or 2000 degrees C min(-1)). Although embryo suspensions visibly crystallized during slow cooling at 5 degrees C min(-1), the rate of cooling was not a significant source of variance (P > 0.26). However, the rate of warming was found to have a small but significant effect on embryo survival (P < 0.05). Vitrified embryos exhibited a high rate of development in vivo after transfer to foster mothers (63%). A paired embryo transfer study comparing vitrification in VS3a with conventional slow freezing in 1.5 mol glycerol l(-1) showed no difference in the rate of development in vivo after either cryopreservation method (P > 0.12). These results demonstrate that embryos can be vitrified in solution VS3a by a simple procedure that includes the widest range of cooling and warming conditions reported to date. C1 ST GEORGE HOSP,SCH MED,MRC,EXPTL EMBRYOL & TERATOL UNIT,LONDON SW17 0RE,ENGLAND. RP RALL, WF (reprint author), NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BLDG 14F,ROOM 101,BETHESDA,MD 20892, USA. FU NIA NIH HHS [1 Y01 AG10164] NR 47 TC 46 Z9 48 U1 0 U2 0 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD AUG PY 1994 VL 101 IS 3 BP 681 EP 688 PG 8 WC Reproductive Biology SC Reproductive Biology GA PG484 UT WOS:A1994PG48400025 PM 7966026 ER PT J AU WIGLEY, RD ZHANG, NZ ZENG, QY SHI, CS HU, DW COUCHMAN, K DUFF, IF BENNETT, PH AF WIGLEY, RD ZHANG, NZ ZENG, QY SHI, CS HU, DW COUCHMAN, K DUFF, IF BENNETT, PH TI RHEUMATIC DISEASES IN CHINA - ILAR-CHINA STUDY COMPARING THE PREVALENCE OF RHEUMATIC SYMPTOMS IN NORTHERN AND SOUTHERN RURAL POPULATIONS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE CHINA; PREVALENCE; RHEUMATISM; ARTHRITIS; POPULATION ID ARTHRITIS; AUSTRALIA AB Objective. To determine the prevalence of rheumatic diseases in Han Chinese in north and south China. Methods. Samples of 4192 adults in the Beijing (north) and 5057 in the Shantou (south) areas, based on village administration registers, were studied. The same questionnaire was administered by doctors who then examined those with rheumatic symptoms. One observer (QYZ) took part in both studies. Results. The prevalence of definite rheumatoid arthritis (RA) was 0.3 4% (95 % CI; 0.20-0.51) in the north and 0.32 % (0.16-0.47) in the south. Ankylosing spondylitis (AS) was noted in 0.26 %; of both samples (95 % CI; 0.11-0.32 north and 0.14-0.40 south). Only 3 cases of systemic lupus erythematosus (SLE) in the north and one in the south were identified, General rheumatic pain was reported more frequently in the north. Lumbar problems were recorded on examination 5 times more frequently in the north than in the south [men, 25 %:5.3 %; women 38 %:6.5 %] and knee problems 10 times more frequently [men, 24 %:1.8 %; women, 36 %:3.4 %] in the north. The difference was greatest in the 55 to 64 year age group. Conclusion. The prevalence of RA was similar to that in other rural populations and Japan, but only half that reported from other industrialized communities. The prevalence of AS was similar to that in most Caucasian populations. SLE was too infrequent to establish a prevalence with confidence, but did not differ from that in other populations. A study is planned in the south to assess the contribution of interobserver error and/or differences in cultural response to the north/south differences observed in the prevalence of general rheumatic symptoms and back pain. C1 PUBL HOSP,WHO,COLLABORATING CTR,PALMERSTON NORTH,NEW ZEALAND. BEIJING UNION MED COLL,DEPT MED,BEIJING,PEOPLES R CHINA. SHANTOU UNIV,COLL MED,SHANTOU,PEOPLES R CHINA. CHUI YANG LIU HOSP,BEIJING,PEOPLES R CHINA. UNIV MICHIGAN,DEPT MED,DIV GERIATR,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT GERIATR,ANN ARBOR,MI 48109. NIDDKD,EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. NR 35 TC 89 Z9 97 U1 0 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 AUG PY 1994 VL 21 IS 8 BP 1484 EP 1490 PG 7 WC Rheumatology SC Rheumatology GA PA712 UT WOS:A1994PA71200019 PM 7983651 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD TI APPENDICULAR BONE MASS AND OSTEOARTHRITIS OF THE HANDS IN WOMEN - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE EPIDEMIOLOGY; ETIOLOGY; OSTEOARTHRITIS; OSTEOPOROSIS ID OSTEO-ARTHRITIS; 2ND METACARPAL; EPIDEMIOLOGY; PREVALENCE; DENSITY; HIP; OSTEOPOROSIS; FEMUR AB Objective. The association of appendicular bone mass with hand osteoarthritis (OA) was studied in 238 Caucasian female participants aged 40 and above in the Baltimore Longitudinal Study of Aging. Methods. Bilateral hand radiographs taken between 1978 and 1991 were read for grade of OA using Kellgren-Lawrence scales. Two measures of appendicular bone mass, percent cortical area of the second metacarpal and bone mineral density of the distal radius measured with single photon absorptiometry, were assessed at the same visit. Results. Bivariate analyses showed that increasing grade of hand OA was associated with increasing age and decreasing bone mass as measured by both techniques. After adjustment for age and body mass index, however, neither of these measures of appendicular bone mass remained significantly associated with grade of hand OA. Conclusion. Our data fail to support the hypothesis that increased appendicular bone mass is associated with hand OA in women. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV SKELETAL RADIOL,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. RP HOCHBERG, MC (reprint author), UNIV MARYLAND,SCH MED,DEPT MED,DIV RHEUMATOL & CLIN IMMUNOL,PROFESS BLDG,419 REDWOOD ST,BALTIMORE,MD 21201, USA. NR 36 TC 40 Z9 43 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 1994 VL 21 IS 8 BP 1532 EP 1536 PG 5 WC Rheumatology SC Rheumatology GA PA712 UT WOS:A1994PA71200028 PM 7983660 ER PT J AU SLESINKI, MJ ORENSTEIN, DM AF SLESINKI, MJ ORENSTEIN, DM TI HIGH-FAT VS LOW-FAT DIETS FOR PATIENTS WITH CYSTIC-FIBROSIS - REPLY SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Correction, Addition C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. CHILDRENS HOSP,PITTSBURGH,PA 15213. RP SLESINKI, MJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 1994 VL 94 IS 8 BP 834 EP 834 DI 10.1016/0002-8223(94)92355-8 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PC114 UT WOS:A1994PC11400005 ER PT J AU PAHOR, M GURALNIK, JM SALIVE, ME CHRISCHILLES, EA MANTO, A WALLACE, RB AF PAHOR, M GURALNIK, JM SALIVE, ME CHRISCHILLES, EA MANTO, A WALLACE, RB TI DISABILITY AND SEVERE GASTROINTESTINAL HEMORRHAGE - A PROSPECTIVE-STUDY OF COMMUNITY-DWELLING OLDER PERSONS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ANTI-INFLAMMATORY DRUGS; BLEEDING PEPTIC-ULCER; PHYSICAL-ACTIVITY; ESTABLISHED POPULATIONS; DIVERTICULAR-DISEASE; HEALTH-STATUS; LOW-RISK; ASPIRIN; EPIDEMIOLOGY; MORTALITY AB OBJECTIVE: To describe the occurrence of severe gastrointestinal bleeding in community-dwelling older persons and to examine whether disability is a risk factor for this life-threatening condition independent of other known predictors. DESIGN: Prospective cohort survey. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). PARTICIPANTS: 8205 persons age greater than or equal to 68 years. MEASUREMENTS: The hospital discharge diagnoses provided by the Medicare Provider Analysis and Review files and the death certificates were prospectively surveyed for 3 years. Those with at least 1 discharge diagnosis of gastrointestinal bleeding and who received a blood transfusion or died were identified as cases of severe gastrointestinal hemorrhage. Physical disability, cognitive function, smoking and alcohol intake habits, body mass index, blood pressure, chronic conditions, number of hospital admissions in past year and medications taken were assessed at baseline. RESULTS: The occurrence rate of severe gastrointestinal bleeding was 10.8 per 1000 person-years (241 events/22,277 person-years). In proportional hazards regression models, compared with no disability, greater than or equal to 1 disabilities in the Rosow-Breslau scale (RR = 2.1, 95% CI = 1.5-2.9), and greater than or equal to 1 ADLs limitations (RR = 3.1, 95% CI = 2.1-4.6) independently predicted gastrointestinal hemorrhage after adjusting for age, gender, body mass index, comorbidity, number of hospital admissions, blood pressure, intake of coumarin, corticosteroids, aspirin and other nonsteroidal antiinflammatory drugs. CONCLUSIONS: In this prospective analysis, disability is an independent predictor of gastrointestinal hemorrhage. Further studies are needed to explain the mechanisms by which disability may cause gastrointestinal hemorrhage. Because physical disability is potentially modifiable, strategies to lower the risk of gastrointestinal bleeding should be evaluated. C1 UNIV CATTOLICA SACRO CUORE, DEPT GERONTOL, I-00168 ROME, ITALY. NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, BETHESDA, MD 20892 USA. UNIV IOWA, DEPT PREVENT MED & ENVIRONM HLTH, IOWA CITY, IA 52242 USA. NR 56 TC 30 Z9 30 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1994 VL 42 IS 8 BP 816 EP 825 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PA325 UT WOS:A1994PA32500003 PM 8046191 ER PT J AU SCHMITT, JM KNUTTEL, A YADLOWSKY, M AF SCHMITT, JM KNUTTEL, A YADLOWSKY, M TI CONFOCAL MICROSCOPY IN TURBID MEDIA SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID BIOLOGICAL TISSUES; OPTICAL-PROPERTIES; IMAGE-FORMATION; PROPAGATION; COHERENCE; DETECTOR AB We examine the performance of confocal microscopes designed for probing structures embedded in turbid media. A heuristic scheme is described that combines a numerical Monte Carlo simulation of photon transport in a turbid medium with a geometrical ray trace through the confocal optics. To show the effects of multiple scattering on depth discrimination, we compare results from the Monte Carlo simulations and scalar diffraction theory. Experimental results showing the effects of the pinhole diameter and other variables on imaging performance at various optical depths in suspensions of polystyrene microspheres were found to correspond well with the Monte Carlo simulations. The major conclusion of the paper is that the trade-off between signal level and background scattered-light rejection places a fundamental limit on the sectioning capability of the microscope. C1 NHLBI,CELLULAR BIOL LAB,BETHESDA,MD 20892. RP SCHMITT, JM (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 10,BETHESDA,MD 20892, USA. NR 25 TC 123 Z9 126 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD AUG PY 1994 VL 11 IS 8 BP 2226 EP 2235 DI 10.1364/JOSAA.11.002226 PG 10 WC Optics SC Optics GA NZ484 UT WOS:A1994NZ48400007 PM 7931759 ER PT J AU PALMER, WG ANDREWS, AW MELLINI, D TERRA, JA HOFFMANN, FJ HOKE, SH AF PALMER, WG ANDREWS, AW MELLINI, D TERRA, JA HOFFMANN, FJ HOKE, SH TI MUTAGENICITY OF PARTICULATE-EMISSIONS FROM THE M16 RIFLE - VARIATION WITH PARTICLE-SIZE SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID FLY-ASH; HYDROCARBONS AB Emissions generated by firing the M16 rifle with the propellant WC844 in a combustion chamber designed to simulate conditions of actual use were tested for mutagenic activity in the Salmonella/Ames assay. Dimethyl sulfoxide extracts of emissions collected from either the breech or muzzle end of the rifle were mutagenic in three strains of Salmonella (TA1537, TA1538, and TA98) both in the presence and absence of metabolic activation systems (S9). The extracts were negative in strains TA100 and TA102. Aerosols generated by firing the M16 rifle were fractionated according to aerodynamic diameter. Submicrometer particles were far more mutagenic than particles with aerodynamic diameters between 1 and 15 mu m. The mutagens associated with the smaller particles were more active in the presence of S9, while extracts of larger particles were as active, or more active, in the absence of S9. Heavier particles, which settled rapidly out of the airstream, were not mutagenic. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RP PALMER, WG (reprint author), USA,BIOMED RES & DEV LAB,BLDG 568,FT DETRICK,FREDERICK,MD 21702, USA. RI Hoke, Robert/F-4943-2010 NR 15 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG PY 1994 VL 42 IS 4 BP 423 EP 433 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PB413 UT WOS:A1994PB41300005 PM 8051716 ER PT J AU PRIOLA, SA CAUGHEY, B RACE, RE CHESEBRO, B AF PRIOLA, SA CAUGHEY, B RACE, RE CHESEBRO, B TI HETEROLOGOUS PRP MOLECULES INTERFERE WITH ACCUMULATION OF PROTEASE-RESISTANT PRP IN SCRAPIE-INFECTED MURINE NEUROBLASTOMA-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID GERSTMANN-STRAUSSLER SYNDROME; CREUTZFELDT-JAKOB DISEASE; PRION PROTEIN; INCUBATION PERIOD; DIFFERENT STRAINS; MISSENSE VARIANT; LEUKEMIA-VIRUS; MOUSE SCRAPIE; MICE; AGENT AB Mutations within a host cellular protein, PrP, have been associated with disease in the transmissible spongiform encephalopathies. Murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant PrP (PrP-res), the abnormal form of PrP associated with disease in the transmissible spongiform encephalopathies. These cells provide a controlled system in which to study the molecular interactions which are important in the formation of PrP-res. We have expressed recombinant PrP molecules in mouse scrapie-infected murine neuroblastoma cells and assayed the effect of these heterologous PrP genes on the formation and accumulation of PrP-res. The results demonstrate that expression of heterologous PrP molecules which differ from the endogenous PrP by as little as one amino acid can profoundly interfere with the overall accumulation of PrP-res. The data suggest that precise interactions between homologous PrP molecules are important in PrP-res accumulation and that heterologous PrP molecules can block these interactions. RP PRIOLA, SA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 46 TC 117 Z9 118 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 4873 EP 4878 PG 6 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800018 PM 7913509 ER PT J AU PERRY, LL MIYAZAWA, M HASENKRUG, K WEHRLY, K DAVID, CS CHESEBRO, B AF PERRY, LL MIYAZAWA, M HASENKRUG, K WEHRLY, K DAVID, CS CHESEBRO, B TI CONTRASTING EFFECTS FROM A SINGLE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULE (H-2E) IN RECOVERY FROM FRIEND-VIRUS LEUKEMIA SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED LEUKEMIA; CELL-SURFACE ANTIGENS; HOST GENETIC-CONTROL; MONOCLONAL-ANTIBODIES; T-CELL; CLONAL DELETION; MOUSE H-2; MICE; IDENTIFICATION; RECOMBINANT AB Resistance to erythroleukemia induced by infection with the Friend virus complex (FV) has been mapped to several genes residing both within and outside the murine major histocompatibility complex (MHC). MHC genes located in the A, D, and Qa/Tla regions of the murine H-2 complex have been shown to affect disease resistance through their capacity to regulate various aspects of the host immune response to viral antigens. This study establishes H-2E as the fourth MHC locus controlling immunological resistance to FV. Our investigation into the role of H-2E molecules revealed two distinct and opposite effects on recovery from Friend disease. H-2(b/b) mice normally lack a functional E gene product and are resistant to high doses of FV. The expression of H-2E molecules in H-2 recombinant or transgenic mice of this genotype resulted in a significant decrease in spontaneous recovery from FV-induced leukemia. In contrast, H-2E expression also appeared to influence recovery from Friend disease in a positive manner, since blocking these molecules with anti-E antibodies in vivo significantly decreased recovery from Friend disease. The data indicate that the positive effects of H-2E molecules derive from their function as restriction elements for helper T-cell recognition of the viral envelope glycoprotein, and eve postulate that the negative effects are due to H-2E-dependent deletions in the T-cell repertoire during development. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. FU NCI NIH HHS [CA 24473] NR 37 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 4921 EP 4926 PG 6 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800023 PM 8035490 ER PT J AU GOTTLIEB, J CHALLBERG, MD AF GOTTLIEB, J CHALLBERG, MD TI INTERACTION OF HERPES-SIMPLEX VIRUS TYPE-1 DNA-POLYMERASE AND THE UL42 ACCESSORY PROTEIN WITH A MODEL PRIMER TEMPLATE SO JOURNAL OF VIROLOGY LA English DT Article ID CELL NUCLEAR ANTIGEN; REPLICATION FACTOR-C; TEMPERATURE-SENSITIVE MUTANTS; ESCHERICHIA-COLI; BINDING PROTEIN; GENETIC-ANALYSIS; III HOLOENZYME; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL INTERACTION; KLENOW FRAGMENT AB Genetic and biochemical studies have shown that the products of the herpes simplex virus type 1 (HSV-1) DNA polymerase (UL30) and UL42 genes are both required for viral DNA replication. A number of studies have previously suggested that these two proteins specifically interact, and more recent studies have confirmed that the viral DNA polymerase from HSV-1-infected cells consists of a heterodimer of the UL30 (Pol; the catalytic subunit) and UL42 polypeptides. A comparison of the catalytic properties of the Pol-UL42 complex with those of the isolated subunits of the enzyme purified from recombinant baculovirus-infected insect cells indicated that the Pol-UL42 complex is more highly processive than Pol alone on singly primed M13 single-stranded substrates. The results of these studies are consistent with the idea that the UL42 polypeptide is an accessory subunit of the HSV-1 DNA polymerase that acts to increase the processivity of polymerization. Preliminary experiments suggested that the increase in processivity was accompanied by an increase in the affinity of the polymerase for the ends of linear duplex DNA. We have further characterized the effect of the UL42 polypeptide on a defined hairpin primer template substrate. Gel shift and filler binding studies show that the affinity of the Pol catalytic subunit for the 3' terminus of the primer template increases 10-fold in the presence of UL42. DNase I footprinting experiments indicate that the Pol catalytic subunit binds to the primer template at a position that protects 14 bp of the 3' duplex region and an adjacent 18 bases of the single-stranded template. The presence of the UL42 polypeptide results in the additional protection of a contiguous 5 to 14 bp in the duplex region but does not affect the 5' position of the Pol subunit. Free UL42 protects the entire duplex region of the substrate but does not bind to the single-stranded region. Taken together, these results suggest that the increase in processivity in the presence of UL42 is related to the double-stranded DNA-binding activity of free UL42 and that the role of UL42 in the DNA polymerase complex is to act as a clamp, decreasing the probability that the polymerase mill dissociate from the template after each cycle of catalysis. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 63 TC 46 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 4937 EP 4945 PG 9 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800025 PM 8035492 ER PT J AU FU, W GORELICK, RJ REIN, A AF FU, W GORELICK, RJ REIN, A TI CHARACTERIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DIMERIC RNA FROM WILD-TYPE AND PROTEASE-DEFECTIVE VIRIONS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CYS-HIS BOX; GENOMIC RNA; NUCLEOCAPSID PROTEIN; CIS ELEMENTS; VIRAL-RNA; DIMERIZATION; INVITRO; MUTANTS; HIV-1 AB We have characterized the dimeric genomic RNA in particles of both wild-type and protease (PR)-deficient human immunodeficiency virus type 1 (HIV-1). We found that the dimeric RNA isolated from PR- mutant virions has a lower mobility in nondenaturing gel electrophoresis than that from wild-type virions. It also dissociates into monomers at a lower temperature than the wild-type dimer. Thus, the dimer in PR(-) particles is in a conformation different from that in wild-type particles. These results are quite similar to recent findings on Moloney murine leukemia virus and suggest that a postassembly, PR-dependent maturation event is a common feature in genomic RNAs of retroviruses. We also measured the thermal stability of the wild-type and PR(-) dimeric RNAs under different ionic conditions. Both forms of the dimer were stabilized by increasing Na+ concentrations. However, the melting temperatures of the two forms were not significantly affected by the identity of the monovalent cation present in the incubation buffer. This observation is in contrast with recent reports on dimers formed in vitro from short segments of HIV-1 sequence: the latter dimers are specifically stabilized by K+ ions. K+ stabilization of dimers formed in vitro has been taken as evidence for the presence of guanine quartet structures. The results suggest that guanine quartets are not involved in the structure linking full-length, authentic genomic RNA of HIV-1 into a dimeric structure. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 38 TC 212 Z9 213 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 AUG PY 1994 VL 68 IS 8 BP 5013 EP 5018 PG 6 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800034 PM 8035501 ER PT J AU MUKHOPADHYAYA, R RICHARDSON, J NAZAROV, V CORBIN, A KOLLER, R SITBON, M WOLFF, L AF MUKHOPADHYAYA, R RICHARDSON, J NAZAROV, V CORBIN, A KOLLER, R SITBON, M WOLFF, L TI DIFFERENT ABILITIES OF FRIEND MURINE LEUKEMIA-VIRUS (MULV) AND MOLONEY MULV TO INDUCE PROMONOCYTIC LEUKEMIA ARE DUE TO DETERMINANTS IN BOTH PSI-GAG-PR AND ENV REGIONS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; DISEASE SPECIFICITY; C-MYB; NONDEFECTIVE FRIEND; MESSENGER-RNA; SARCOMA-VIRUS; BALB/C MICE; 3' END; SEQUENCES; GENOME AB Moloney murine leukemia virus (M-MuLV) is capable of inducing promonocytic leukemia in 50% of adult BALB/c mice that have received peritoneal injections of pristane, but Friend MuLV strain 57 (F-MuLV) is nonleukemogenic under similar conditions. It was shown earlier that these differences could not be mapped to the U3 region of the virus long terminal repeat, indicating the probable influence of structural genes and/or R-U5 sequences. In this study, reciprocal chimeras containing exchanged structural genes and R-U5 sequences from these two closely related viruses were analyzed for differences in ability to induce disease. Results showed that two regions of F-MuLV, Psi-gag-PR and env, when substituted for those of M-MuLV were dramatically disease attenuating. The 5'-most region, which is widely distributed, overlaps with the 5' end of the env intron and includes the RNA packaging region, Psi, the entire gag coding region, and the viral protease coding region (PR) of pol. It was also found that reciprocal constructs having substitutions of both of these regions of M-MuLV in an F-MuLV background allowed full reestablishment of promonocytic leukemia. These leukemias were positive for c-myb rearrangements which are characteristic of M-MuLV-induced promonocytic leukemias. Neither region alone, however, was sufficient to produce disease with a greater incidence than 13%. Further studies demonstrated that the inability of viruses with Psi, gag, PR, or env sequences from F-MuLV to induce leukemia in this model system was not due to their inability to replicate in hematopoietic tissue, to integrate into the c-myb locus early on after infection in vivo, or to express gag-myb mRNA characteristic of M-MuLV-induced preleukemic cells and acute leukemia. C1 NCI,GENET LAB,BETHESDA,MD 20892. INST COCHIN GENET MOLEC,INSERM,U363,PARIS,FRANCE. RI Sitbon, Marc/A-6771-2010 OI Sitbon, Marc/0000-0003-3616-2338 NR 39 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 5100 EP 5107 PG 8 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800044 PM 7518530 ER PT J AU RHEE, SS MARSH, JW AF RHEE, SS MARSH, JW TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF-INDUCED DOWN-MODULATION OF CD4 IS DUE TO RAPID INTERNALIZATION AND DEGRADATION OF SURFACE CD4 SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN KINASE P56LCK; CELL-SURFACE; HIV-1 NEF; AIDS VIRUS; T-CELLS; GLYCOPROTEIN PRECURSOR; ENDOPLASMIC-RETICULUM; NUCLEOTIDE-SEQUENCE; PLASMA-MEMBRANE; GENE-PRODUCT AB Human immunodeficiency virus type 1 (HIV-1) Nef is a myristylated protein with a relative molecular mass of 27 kDa, is localized to the cytoplasmic surfaces of cellular membranes, and has been reported to down-modulate CD4 in human T cells. To understand the mechanism of HIV-1 Nef-mediated down-modulation of cell surface CD4, we expressed Nef protein in human T-cell line VB. Expression of HIV-1 Nef protein down-modulated surface CD4 molecules. In pulse-chase experiments, CD4 molecules in Nef expressing cells were synthesized at normal levels. However, the bulk of newly synthesized CD4 protein was degraded with a half-life of approximately 6 h, compared with the 24-h half-life in control cells. This Nef-induced acceleration of CD4 turnover was inhibited by lysosomotropic agents NH4Cl and chloroquine as well as by the protease inhibitor leupeptin. Surface CD4 biotinylation experiments demonstrated that CD4 molecules in Nef-expressing T cells are transported to the plasma membrane with normal kinetics but are then rapidly internalized. Therefore, HIV-1 Nef-induced down-modulation of CD4 is due to rapid internalization of surface CD4 and subsequent degradation by an acid-dependent process, potentially lysosomal. Additionally, in a Nef-expressing cell, we find accelerated dissociation of the T-cell tyrosine kinase p56(lck) and CD4 but only after the complex reaches the plasma membrane. This implies that HIV-1 Nef protein might play a role in triggering a series of T-cell activation-like events, which contribute to p56(lck) dissociation and internalization of surface CD4 molecules. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 66 TC 159 Z9 159 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 5156 EP 5163 PG 8 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800050 PM 8035515 ER PT J AU LAVIGNON, M WALKER, JL PERRYMAN, SM MALIK, FG KHAN, AS THEODORE, TS EVANS, LH AF LAVIGNON, M WALKER, JL PERRYMAN, SM MALIK, FG KHAN, AS THEODORE, TS EVANS, LH TI CHARACTERIZATION OF EPITOPES DEFINING 2 MAJOR SUBCLASSES OF POLYTROPIC MURINE LEUKEMIA VIRUSES (MULVS) WHICH ARE DIFFERENTIALLY EXPRESSED IN MICE INFECTED WITH DIFFERENT ECOTROPIC MULVS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; FOCUS-FORMING VIRUSES; ENV GENE; MONOCLONAL-ANTIBODIES; SPONTANEOUS LYMPHOMAS; NUCLEOTIDE-SEQUENCE; ENVELOPE GENE; MCF VIRUSES; AKR/J MICE; CELL LINES AB Polytropic murine leukemia viruses (MuLVs) arise in mice by recombination of ecotropic MuLVs with endogenous retroviral envelope genes and have been implicated in the induction of hematopoietic proliferative diseases. Inbred mouse strains contain many endogenous sequences which are homologous to the polytropic env genes; however, the extent to which particular sequences participate in the generation of the recombinants is unknown, Previous studies have established antigenic heterogeneity among the env genes of polytropic MuLVs, which may reflect recombination with distinct endogenous genes. In the present study, we have examined many polytropic MuLVs and found that nearly all isolates fall into two mutually exclusive antigenic subclasses on the basis of the ability of their SU proteins to react with one of two monoclonal antibodies, termed Hy 7 and MAb 516. Epitope-mapping studies revealed that reactivity to the two antibodies is dependent on the identity of a single amino acid residue encoded in a variable region of the receptor-binding domain of the env gene. This indicated that the two antigenic subclasses of MuLVs arose by recombination with distinct sets of endogenous genes. Evaluation of polytropic MuLVs in mice revealed distinctly different ratios of the two subclasses after inoculation of different ecotropic MuLVs, suggesting that individual ecotropic MuLVs preferentially recombine with distinct sets of endogenous polytropic env genes. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. US FDA,CTR BIOL EVALUAT & RES,RETROVIRUS RES LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 53 TC 10 Z9 10 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 AUG PY 1994 VL 68 IS 8 BP 5194 EP 5203 PG 10 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800054 PM 7518532 ER PT J AU FREED, EO ORENSTEIN, JM BUCKLERWHITE, AJ MARTIN, MA AF FREED, EO ORENSTEIN, JM BUCKLERWHITE, AJ MARTIN, MA TI SINGLE AMINO-ACID CHANGES IN THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MATRIX PROTEIN BLOCK VIRUS PARTICLE-PRODUCTION SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; RECOMBINANT VACCINIA VIRUS; INFECTED INSECT CELLS; GAG PRECURSOR PROTEIN; PLASMA-MEMBRANE; INTRACELLULAR-TRANSPORT; MAMMALIAN-CELLS; AVIAN-SARCOMA; C RETROVIRUS; N-TERMINUS AB The matrix protein of human immunodeficiency virus type I is encoded by the amino-terminal portion of the Gag precursor and is postulated to be involved in a variety of functions in the virus life cycle. To define domains and specific amino acid residues of the matrix protein that are involved in virus particle assembly, we introduced 35 amino acid substitution mutations in the human immunodeficiency virus type 1 matrix protein. Using reverse transcriptase and radioimmunoprecipitation analyses and transmission electron microscopy, we assessed the mutants for their ability to form virus particles and to function in the infection process. This study has identified several domains of the matrix protein in which single amino acid substitutions dramatically reduce the efficiency of virus particle production. These domains include the six amino-terminal residues of matrix, the region of matrix between amino acids 55 and 59, and the region between amino acids 84 and 95. Single amino acid substitutions in one of these domains (between matrix amino acids 84 and 88) result in a redirection of the majority of virus particle formation to sites within cytoplasmic vacuoles. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,SCH MED,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20854. RP FREED, EO (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 307,BETHESDA,MD 20892, USA. NR 78 TC 241 Z9 243 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 AUG PY 1994 VL 68 IS 8 BP 5311 EP 5320 PG 10 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800072 PM 8035531 ER PT J AU CONNORS, M GIESE, NA KULKARNI, AB FIRESTONE, CY MORSE, HC MURPHY, BR AF CONNORS, M GIESE, NA KULKARNI, AB FIRESTONE, CY MORSE, HC MURPHY, BR TI ENHANCED PULMONARY HISTOPATHOLOGY INDUCED BY RESPIRATORY SYNCYTIAL VIRUS (RSV) CHALLENGE OF FORMALIN-INACTIVATED RSV-IMMUNIZED BALB/C MICE IS ABROGATED BY DEPLETION OF INTERLEUKIN-4 (IL-4) AND IL-10 SO JOURNAL OF VIROLOGY LA English DT Note ID CELL-MEDIATED-IMMUNITY; MESSENGER-RNA EXPRESSION; CD4+ T-CELLS; COTTON RATS; RESPONSES; GLYCOPROTEIN; TH1; INDUCTION; PATTERNS; PROTEINS AB In previous studies, children immunized with a formalin-inactivated respiratory syncytial virus vaccine (FI-RSV) developed severe pulmonary disease with greater frequency than did controls during subsequent natural RSV infection. In earlier efforts to develop an animal model for this phenomenon, extensive pulmonary histopathology developed in FI-RSV-immunized cotton rats and mice subsequently challenged with RSV. In mice, depletion of CD4(+) T cells at the time of RSV challenge completely abrogated this histopathology. Furthermore, the predominant cytokine mRNA present in lungs of FI-RSV-immunized mice during subsequent infection with RSV was that characteristically secreted by Th2 T cells, namely interleukin-4 (IL-4). In the present studies, we sought to determine the relative contributions of gamma interferon (IFN-gamma), IL-2, IL-4, and IL-10 to the lymphocytic infiltration into the lungs observed following RSV challenge of mice previously immunized with FI-RSV. Mice previously immunized with FI-RSV or infected with RSV were depleted of IFN-gamma, IL-2, IL-4, or IL-10 immediately before RSV challenge, and the magnitude of inflammatory cell infiltration around bronchioles and pulmonary blood vessels was quantified. The phenomenon of pulmonary-histopathology potentiation by FI-RSV was reproduced in the present study, thereby allo,wing us to investigate the effect of cytokine depletion on the process. Simultaneous depletion of both IL-4 and IL-10 completely abrogated pulmonary histopathology in FI-RSV-immunized mice. Depletion of IL-4 alone significantly reduced bronchiolar, though not perivascular, histopathology. Depletion of IL-10 alone had no effect. Depletion of IFN-gamma, IL-2, or both together had no effect on the observed histopathology. These data indicate that FI-RSV immunization primes for a Th2-, IL-4-, and IL-10-dependent inflammatory response to subsequent RSV infection. It is possible that this process played a role in enhanced disease observed in infants and children immunized with FI-RSV. C1 NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 32 TC 188 Z9 193 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1994 VL 68 IS 8 BP 5321 EP 5325 PG 5 WC Virology SC Virology GA NW978 UT WOS:A1994NW97800073 PM 8035532 ER PT J AU CHAMPOUX, M SUOMI, SJ SCHNEIDER, ML AF CHAMPOUX, M SUOMI, SJ SCHNEIDER, ML TI TEMPERAMENT DIFFERENCES BETWEEN CAPTIVE INDIAN AND CHINESE-INDIAN HYBRID RHESUS MACAQUE NEONATES SO LABORATORY ANIMAL SCIENCE LA English DT Article ID MONKEYS MACACA-MULATTA; SQUIRREL-MONKEYS; ASSOCIATIVE PROCESSES; BEHAVIORAL-RESPONSES; PRENATAL STRESS; PERSONALITY; SCIUREUS; INFANTS AB Anecdotal evidence has accumulated from research and animal care personnel regarding the aggressive behavior reported in captive rhesus macaques originating in China. In this study, we compared neonatal temperament, activity, and neuromotor reflexes in 13 Chinese-Indian hybrid and 29 Indian-derived nursery-reared infants. Neonatal assessments were conducted on days 7, 14, 21, and 30, using a test based on the Brazelton Neonatal Assessment Scale developed for use in human newborns. Hybrid infants had lower scores for all items pertaining to orientation and ability to sustain attention. They were also rated as more temperamentally reactive and irritable than the Indian-derived infants. These results suggest that constitutional factors may underlie some of the behavioral differences observed in Chinese- and Indian-origin adults and that these qualities emerge very early in life. C1 UNIV WISCONSIN,DEPT THERAPEUT SCI,MADISON,WI 53706. RP CHAMPOUX, M (reprint author), NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837, USA. FU NIMH NIH HHS [MH48417-02]; PHS HHS [9102] NR 44 TC 48 Z9 48 U1 1 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD AUG PY 1994 VL 44 IS 4 BP 351 EP 357 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA PD469 UT WOS:A1994PD46900010 PM 7983847 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI ANTIPHOSPHOLIPID ANTIBODY - FUTURE-DEVELOPMENTS SO LUPUS LA English DT Article; Proceedings Paper CT 6th International Symposium on Antiphospholipid Antibodies CY SEP 14-17, 1994 CL LEUVEN, BELGIUM DE ANTIPHOSPHOLIPID ANTIBODY; FUTURE ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTICARDIOLIPIN ANTIBODIES; ANTICOAGULANT ACTIVITY; BETA-2-GLYCOPROTEIN-I; THROMBOSIS; PROTEIN AB In September 1991, an NIH workshop on molecular and biological aspects of antiphospholipid antibodies (aPL) identified questions for future studies: are the antibodies defined by the ELISA and by the lupus anticoagulant tests the same? Is aPL directly responsible for disease? What is the antigen? What drives the production of aPL? What is the role of beta(2)-glycoprotein I? What accounts for patient heterogeneity? Can a satisfactory animal model be developed? The NIH workshop did not address important clinical questions, including those of pathogenesis and treatment. In 1994 many of these questions have at least partial answers. beta(2)-glycoprotein I appears to be an obligatory component of the antigen, abnormal coagulation is the probable central pathogenic event and animal models now exist. There are still critical unknowns that define a future research agenda: the genetics of the aPL syndrome, the relationship of aPL to SLE and mechanisms of pathogenesis (including why clotting is episodic and what is the cellular or anatomical location of the initial injury). Despite a decade of clinical studies, risk prediction for defined patient groups is only now beginning to be studied. There are still almost no randomized, prospective, controlled treatment trials on any aspect of the syndrome nor are there definitive answers regarding which among antiplatelet, anticoagulant or antithrombin therapies is superior, what is the role of immunosuppressive therapy and what experimental therapies might be introduced. The molecular biology of the antigen-antibody interaction will soon be fully understood, then the cellular and the organism biology. Definitive treatment interventions may await this understanding but adequate therapies are available al this time to conduct important and effective prospective clinical trials. RP LOCKSHIN, MD (reprint author), NIAMSD,BLDG 31,ROOM 4C-32,BETHESDA,MD 20892, USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0961-2033 J9 LUPUS JI Lupus PD AUG PY 1994 VL 3 IS 4 BP 309 EP 311 DI 10.1177/096120339400300420 PG 3 WC Rheumatology SC Rheumatology GA PJ819 UT WOS:A1994PJ81900020 PM 7804322 ER PT J AU LUEDERS, KK FRANKEL, WN AF LUEDERS, KK FRANKEL, WN TI MAPPING OF MOUSE INTRACISTERNAL A-PARTICLE PROVIRAL MARKERS IN AN INTERSPECIFIC BACKCROSS SO MAMMALIAN GENOME LA English DT Article ID GENETIC-LINKAGE; IDENTIFICATION; ELEMENTS; FAMILY; PROBES AB We present a linkage map of intracisternal A-particle (IAP) proviral loci. The IAP family consists of 2000 endogenous proviral elements that are widely dispersed in the mouse genome. The map was constructed by using an interspecific backcross and markers defined by oligonucleotide probes specific for subclasses of expressed IAP elements. In genomic DNA from C57BL/6J mouse, these probes each detected from 12 to 44 HindIII restriction fragments that represent junctions between proviral and 5'-flanking DNA. The fragments have characteristic strain distribution patterns (SDPs) that are particularly polymorphic in the DNAs of C57BL/6J and Mus spretus mice used for the backcross. IAP loci were placed on.the map by comparison of their distribution patterns with those of known genetic markers in the backcross. The map includes 51 IAP loci that have not been previously mapped and 23 IAP proviruses that had been previously mapped in recombinant inbred (RI) strains. Comparable map positions were obtained with the IAP markers in the interspecific backcross and the RI strains. The mapped IAP loci were widely dispersed on the X Chromosome (Chr) and all of the autosomes except Chrs 9 and 19, providing useful genetic markers for linkage studies. C1 JACKSON LAB,BAR HARBOR,ME 04609. RP LUEDERS, KK (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-03,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS31348] NR 14 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1994 VL 5 IS 8 BP 473 EP 478 DI 10.1007/BF00369315 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NZ448 UT WOS:A1994NZ44800002 PM 7949730 ER PT J AU PANDEY, KN ADAMSON, MC GU, YC KOZAK, CA AF PANDEY, KN ADAMSON, MC GU, YC KOZAK, CA TI GENETIC-MAPPING OF THE GENE ENCODING GUANYLATE CYCLASE-A ATRIAL-NATRIURETIC-FACTOR RECEPTOR (NPRA) TO MOUSE CHROMOSOME-3 SO MAMMALIAN GENOME LA English DT Note ID CYCLIC-GMP ACCUMULATION; PEPTIDE RECEPTOR; CROSS-LINKING; MURINE; CELLS; BINDING; FAMILY; STIMULATION; ACTIVATION C1 NIAID,BETHESDA,MD 20892. RP PANDEY, KN (reprint author), MED COLL GEORGIA,SCH MED,DEPT BIOCHEM & MOLEC BIOL,AUGUSTA,GA 30912, USA. FU NICHD NIH HHS [HD 25527] NR 29 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1994 VL 5 IS 8 BP 520 EP 522 DI 10.1007/BF00369325 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NZ448 UT WOS:A1994NZ44800012 PM 7949740 ER PT J AU TRAUB, W ARAD, T VETTER, U WEINER, S AF TRAUB, W ARAD, T VETTER, U WEINER, S TI ULTRASTRUCTURAL STUDIES OF BONES FROM PATIENTS WITH OSTEOGENESIS IMPERFECTA SO MATRIX BIOLOGY LA English DT Article DE APATITE; BIOMINERALIZATION; BONE STRUCTURE; COLLAGEN; OSTEOGENESIS IMPERFECTA ID TENDON COLLAGEN-FIBERS; COMPACT-BONE; CRYSTALS; ORGANIZATION; FIBRILS; GROWTH AB Bone samples from patients suffering from osteogenesis imperfecta (OI) types I, II, III and IV, as well as normal controls, were studied by scanning (SEM) and transmission electron microscopy (TEM). SEM views of normal bone at low magnification show coherent structure, with regular striations due to a lamellar plywood-like arrangement of the mineralized collagen fibrils. Compact lamellar bone was also found in various OI specimens, but in limited disconnected regions separated by open spaces. Furthermore, some OI, but not normal, bones have regions of loose unconnected fibers and others of apparently abnormally dense mineral deposition. High resolution TEM studies of OI bone fragments have served to elucidate the structures of these different textures. There appears to be a substantial, though reduced, proportion of normal lamellar bone even in quite severe OI. However, the regions of loose fibers are largely unmineralized and probably contain abnormal collagen. Other regions are overmineralized, with generally small unorganized apatite crystals deposited onto fibril surfaces or in separate clusters. These structural abnormalities, together with the paucity of normal bone, may explain the fragility of OI bones. C1 NIDR,BETHESDA,MD 20892. HUMBOLDT UNIV BERLIN,CHARITE HOSP,DEPT PEDIAT,BERLIN,GERMANY. RP TRAUB, W (reprint author), WEIZMANN INST SCI,DEPT BIOL STRUCT,IL-76100 REHOVOT,ISRAEL. FU NIDCR NIH HHS [DE 06954] NR 29 TC 62 Z9 62 U1 2 U2 7 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD AUG PY 1994 VL 14 IS 4 BP 337 EP 345 DI 10.1016/0945-053X(94)90200-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PE316 UT WOS:A1994PE31600009 PM 7827757 ER PT J AU SALIVE, ME AF SALIVE, ME TI REFERRAL BIAS IN TERTIARY CARE - THE UTILITY OF CLINICAL EPIDEMIOLOGY SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,SUITE 3C309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 9 TC 10 Z9 10 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 1994 VL 69 IS 8 BP 808 EP 809 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PA219 UT WOS:A1994PA21900019 PM 8035642 ER PT J AU BRAUN, MM TUCKER, MA DEVESA, SS HOOVER, RN AF BRAUN, MM TUCKER, MA DEVESA, SS HOOVER, RN TI SEASONAL-VARIATION IN FREQUENCY OF DIAGNOSIS OF CUTANEOUS MALIGNANT-MELANOMA SO MELANOMA RESEARCH LA English DT Article DE ETIOLOGY; DIAGNOSIS; EPIDEMIOLOGY; MELANOMA; SEASONS; SUNLIGHT AB Incident cases of in situ and invasive cutaneous malignant melanoma diagnosed during 1975-90 were identified through the National Cancer Institute's Surveillance, Epidemiology, and End Results program. We studied the 32 868 white subjects diagnosed with melanoma, who were living in nine cancer registry areas covering approximately 10% of the population of the USA. The summer-to-winter ratio, defined as the ratio of the number of melanomas diagnosed during June to August (summer), to the number of melanomas diagnosed during December to February (winter), was determined according to gender, stage, histologic type and anatomic site. Summer-to-winter ratios were 1.47 (95% confidence interval (CI) 1.37-1.58) for in situ, 1.43 (95% CI 1.38-1.48) for local stage; 1.24 (95% CI 1.12-1.38) for regional stage; and 0.95 (95% CI 0.82-1.11) for distant stage melanoma. For the melanomas staged as local at diagnosis (86% of the invasive melanomas staged), a July peak was observed. For each of the major histological types of local stage melanoma, summer-to-winter ratios were significantly elevated in men (range 1.24-1.41) and women (range 1.44-1.90). For the major anatomic sites (including the head and neck, which are exposed throughout the year) of local stage melanoma, summer-to-winter ratios were elevated for men (range 1.28-1.45) and for women (range 1.31-1.75). Although some of the seasonal variation in frequency of diagnosis of cutaneous melanoma may be due to a greater likelihood of detection during the summer months, when less clothing is worn and more skin is visible, we conclude that the seasonal variation is due at least in part to relatively recent exposure to sun. These findings may hold clues to the last stages of carcinogenesis, and suggest that avoiding excessive exposure to the sun may decrease the risk of melanoma in the short term as well as the long term. RP BRAUN, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 33 Z9 33 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 1994 VL 4 IS 4 BP 235 EP 241 DI 10.1097/00008390-199408000-00005 PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA PC039 UT WOS:A1994PC03900005 PM 7950359 ER PT J AU NORTON, WN BROWN, CR LEWIS, MG RIPPY, MK MARTIN, JE ZACK, PM AF NORTON, WN BROWN, CR LEWIS, MG RIPPY, MK MARTIN, JE ZACK, PM TI CHARACTERIZATION OF SIMIAN IMMUNODEFICIENCY VIRUS (SIV) INFECTED AA-2 CELLS BY SEM AND IMMUNOELECTRON MICROSCOPY SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE B LYMPHOCYTES; AIDS; HIV; IMMUNODEFICIENCY; SCANNING ELECTRON MICROSCOPY; SIV ID SCANNING ELECTRON-MICROSCOPY; SOOTY MANGABEYS; LEUKOCYTES; RHESUS; LINES AB The ultrastructural features of AA-2 cells infected with either of two strains of simian immunodeficiency virus (SIVMne-E11S or SIVSMM-PBj) were examined by scanning electron microscopy (SEM). Transformed CD4+ human B lymphocytes (AA-2) were inoculated with SIV and observed at 2, 4, and 7 days post-inoculation (dPI). Infected AA-2 cells were distinguished by the progressive loss of microvilli, and variable numbers of free or protruding spherical particles measuring 90-120nm in diameter along the cell surface. Syncytial cell formation (complexes of fused cells) and necrotic cells were evident at each time point with the most numerous observations at 7 dPI. While the distribution and severity of the viral induced changes increased with time and affected virtually all cells by 7 dPI, the alterations were detected sooner and were more pronounced in SIVSMM-PBj infected cells. This finding is consistent with the in vivo data from primate studies using the same strains of SIV. Syncytial cells exhibited slight to moderate indentations which appeared to coincide with the boundaries of individual cells forming the complex. The plasma membrane of syncytial cells was relatively smooth and lacked microvilli. Spherical particles and buds protruding from the plasma membrane were predominate features of syncytial cell surfaces. By the employment of antisera generated against whole SIVMne-E11S, both transmission and scanning immunoelectron microscopy confirmed the identity of the spherical structures as free and budding SIV virions. (C) 1994 Wiley-Liss, Inc. C1 HENRY M JACKSON FDN,ROCKVILLE,MD 20850. ELI LILLY & CO,LILLY RES LABS,GREENFIELD,IN 46140. NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. WALTER REED ARMY MED CTR,DIV RETROVIROL,WASHINGTON,DC 20307. RP NORTON, WN (reprint author), SE LOUISIANA UNIV,BOX 335,HAMMOND,LA 70402, USA. NR 16 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 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD AUG 1 PY 1994 VL 28 IS 5 BP 430 EP 439 DI 10.1002/jemt.1070280510 PG 10 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA NU578 UT WOS:A1994NU57800009 PM 7919531 ER PT J AU KELLEHER, M CURTIS, JM SACKS, DL HANDMAN, E BACIC, A AF KELLEHER, M CURTIS, JM SACKS, DL HANDMAN, E BACIC, A TI EPITOPE MAPPING OF MONOCLONAL-ANTIBODIES DIRECTED AGAINST LIPOPHOSPHOGLYCAN OF LEISHMANIA-MAJOR PROMASTIGOTES SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE LEISHMANIA MAJOR; LIPOPHOSPHOGLYCAN; CARBOHYDRATE EPITOPE; MONOCLONAL ANTIBODY; PROMASTIGOTE ID DONOVANI LIPOPHOSPHOGLYCAN; CUTANEOUS LEISHMANIASIS; LINKED OLIGOSACCHARIDES; CELL-LINES; BINDING; MACROPHAGES; EXPRESSION; RECEPTOR; STAGE; ADHESION AB Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this major cell surface glycoconjugate. Epitope mapping of four MAbs, designated 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2, revealed that the phosphorylated oligosaccharide repeat unit PO4-6[Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, P3, is a highly immunogenic epitope which has previously been demonstrated, by chemical analyses, to be a repeat unit specific to L. major. Two antibodies, 4A2-A2 and 5E10-F2, also recognised the repeat unit PO4-6[Ara(beta 1-2)Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, P4a, with less affinity than P3, while 2G11-A3 recognised P4a with greater affinity than for P3. The L. major metacyclic-specific antibody 3F12 only recognised repeat units terminating with arabinose residues. In particular, 3F12 recognised P4a, which is upregulated in metacyclic LPG compared to the procyclic form of the molecule. The oligosaccharides P3, P4a and P5a are specific to L. major LPG. The epitopes of 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2 were found on the cell surface and in the flagellar pocket of both procyclic and metacyclic V121 promastigotes, but were only detected at very low levels on amastigotes. The repeat unit P3 is able to inhibit attachment of procyclic promastigotes to the midgut of the sandfly vector, but neither Fab fragments of the four antibodies nor purified P3 could inhibit attachment of metacyclic promastigotes to the macrophage cell line J774. It was also shown that human sera from patients with cutaneous leishmaniasis recognised purified P3. The data suggests that while P3 is an immunogen in the natural course of infection of the human host, P3 plays no role in attachment and internalisation of promastigotes into the macrophages of the mammalian host. C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC,AUSTRALIA. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV MELBOURNE,SCH BOT,PLANT CELL BIOL RES CTR,MELBOURNE,VIC 3052,AUSTRALIA. OI Bacic, Tony/0000-0001-7483-8605 FU PHS HHS [A1-28962] NR 50 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD AUG PY 1994 VL 66 IS 2 BP 187 EP 200 DI 10.1016/0166-6851(94)90146-5 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA PE321 UT WOS:A1994PE32100001 PM 7808469 ER PT J AU FURTH, PA CHOE, WT REX, JH BYRNE, JC BAKER, CC AF FURTH, PA CHOE, WT REX, JH BYRNE, JC BAKER, CC TI SEQUENCES HOMOLOGOUS TO 5' SPLICE SITES ARE REQUIRED FOR THE INHIBITORY ACTIVITY OF PAPILLOMAVIRUS LATE 3' UNTRANSLATED REGIONS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PRE-MESSENGER-RNA; NUCLEAR RIBONUCLEOPROTEIN PARTICLE; BOVINE PAPILLOMAVIRUS; PREMESSENGER RNA; U1 SNRNP; UPSTREAM SEQUENCES; MOUSE CELLS; POLYADENYLATION SIGNAL; SECONDARY STRUCTURE; TRANSCRIPTION UNIT AB Expression of bovine papillomavirus type 1 (BPV-1) tate genes is limited to terminally differentiated keratinocytes in an infected epithelium. We have previously shown that although the BPV-1 late polyadenylation site is functional in nonpermissive cells, a 53-nucleotide (nt) fragment of the late 3' untranslated region acts posttranscriptionally to reduce polyadenylated cytoplasmic RNA levers. This 53-nt fragment does not appear to function by destabilizing polyadenylated cytoplasmic RNA (P. A. Furth and C. C. Baker, J. Virol. 65:5806-5812, 1991). In this study, we used site-directed mutagenesis and deletion analysis to demonstrate that the sequence AAG/GUAAGU, which is identical to the consensus 5' splice site sequence, was both necessary and sufficient for the inhibitory activity of the 53-nt fragment. Furthermore, base pairing between the 5' end of the U1 small nuclear RNA and this 5' splice site-like sequence was shown to be required for the inhibitory activity in vivo. We have also further mapped the human papillomavirus type 16 late 3' inhibitory element (I. M. Kennedy, J. K. Haddow, and J. B. Clements, J. Virol. 65:2093-2097, 1991) to a 51-nt region containing four overlapping sequence motifs with partial homology to 5' splice sites. Mutation of each of these motifs demonstrated that only one of these motifs is required for the inhibitory activity. However, the presence of the other motifs may contribute to the full inhibitory activity of the element. No BPV-1 or human papillomavirus type 16 mRNAs which are spliced by using the potential 5' splice sites present in the viral late 3' untranslated regions have been identified. This suggests that the primary function of these 5' splice site-like sequences is the inhibition of late gene expression. The most likely mechanism of action of these elements is reduction of polyadenylation efficiency, perhaps through interference with 3'-terminal exon definition. C1 NCI, TUMOR VIRUS BIOL LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV INFECT DIS, BALTIMORE, MD 21201 USA. NR 87 TC 122 Z9 124 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 AUG PY 1994 VL 14 IS 8 BP 5278 EP 5289 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NY429 UT WOS:A1994NY42900027 PM 8035806 ER PT J AU DECHESNE, CA WEI, Q ELDRIDGE, J GANNOUNZAKI, L MILLASSEAU, P BOUGUELERET, L CATERINA, D PATERSON, BM AF DECHESNE, CA WEI, Q ELDRIDGE, J GANNOUNZAKI, L MILLASSEAU, P BOUGUELERET, L CATERINA, D PATERSON, BM TI E-BOX-INDEPENDENT AND MEF-2-INDEPENDENT MUSCLE-SPECIFIC EXPRESSION, POSITIVE AUTOREGULATION, AND CROSS-ACTIVATION OF THE CHICKEN MYOD (CMD1) PROMOTER REVEAL AN INDIRECT REGULATORY PATHWAY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-FACTOR; GENE-EXPRESSION; ACTIN PROMOTER; CARDIAC ACTIN; TRANSCRIPTIONAL ACTIVATION; SKELETAL-MUSCLE; MYOGENIC CELLS; NUCLEAR FACTOR; FACTOR MEF-2; CHAIN GENE AB Members of the MyoD family of gene-regulatory proteins (MyoD, myogenin, myf5, and MRF4) have all been shown not only to regulate the transcription of numerous muscle-specific genes but also to positively autoregulate and cross activate each other's transcription. In the case of muscle-specific genes, this transcriptional regulation can often be correlated with the presence of a DNA consensus in the regulatory region CANNTG, known as an E box. Little is known about the regulatory interactions of the myogenic factors themselves; however, these interactions are thought to be important for the activation and maintenance of the muscle phenotype. We have identified the minimal region in the chicken MyoD (CMD1) promoter necessary for muscle-specific transcription in primary cultures of embryonic chicken skeletal muscle. The CMD1 promoter is silent in primary chick fibroblast cultures and in muscle cell cultures treated with the thymidine analog bromodeoxyuridine. However, CMD1 and chicken myogenin, as well as, to a lesser degree, chicken Myf5 and MRF4, expressed in trans can activate transcription from the minimal CMD1 promoter in these primary fibroblast cultures. Here we show that the CMD1 promoter contains numerous E-box binding sites for CMD1 and the other myogenic factors, as well as a MEF-2 binding site. Surprisingly, neither muscle-specific expression, autoregulation, or cross activation depends upon the presence of these E-box or MEF-2 binding sites in the CMD1 promoter. These results demonstrate that the autoregulation and cross activation of the. chicken MyoD promoter through the putative direct binding of the myogenic basic helix-loop-helix regulatory factors is mediated through an indirect pathway that involves unidentified regulatory elements and/or ancillary factors. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 78 TC 45 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1994 VL 14 IS 8 BP 5474 EP 5486 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NY429 UT WOS:A1994NY42900047 PM 8035824 ER PT J AU MAHER, F SIMPSON, IA AF MAHER, F SIMPSON, IA TI MODULATION OF EXPRESSION OF GLUCOSE TRANSPORTERS GLUT3 AND GLUT1 BY POTASSIUM AND N-METHYL-D-ASPARTATE IN CULTURED CEREBELLAR GRANULE NEURONS SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID GENE-EXPRESSION; XENOPUS OOCYTES; CELL-CULTURE; HIGH K+; BRAIN; SURVIVAL; GLUTAMATE; DEPOLARIZATION; RECEPTORS; DIFFERENTIATION AB Depolarization is known to stimulate neuronal oxidative metabolism. As glucose is the primary fuel for oxidative metabolism in the brain, the entry of glucose into neural cells is a potential control point for any regulatory events in brain metabolism. Therefore, the effects of depolarizing stimuli, high K+ and N-methyl-D-aspartate (NMDA), were examined on the functional expression of glucose transporter isoforms GLUT1 and GLUT3 in primary cultured cerebellar granule neurons. Higher levels of glucose transport activity were observed in neurons cultured in 25 mM KCl (K25) compared to those in 5 and 15 mM KCl (K5 and K15). The elevated glucose transport activity correlated with increased levels of GLUT3 protein and, to a lesser extent, GLUT1. Both GLUT3 and GLUT1 were regulated at the level of mRNA expression. Addition of NMDA to K5 and K15 cultures increased both glucose uptake and GLUT3 protein levels, with smaller changes in GLUT1. NMDA effects were not additive with K25 effects. All these changes were observed only with chronic exposure of neurons to high K+ or NMDA; no acute effects on glucose uptake or transporter expression were found. Thus, chronic depolarization of primary cerebellar granule neurons acts as a stimulus for the expression of the neuronal GLUT3 glucose transporter isoform. (C) 1994 Academic Press, Inc. RP MAHER, F (reprint author), NIDDK,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BLDG 10,ROOM 5N102,BETHESDA,MD 20892, USA. NR 37 TC 29 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD AUG PY 1994 VL 5 IS 4 BP 369 EP 375 DI 10.1006/mcne.1994.1044 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PA999 UT WOS:A1994PA99900009 PM 7804607 ER PT J AU NAGRA, RM HEYES, MP WILEY, CA AF NAGRA, RM HEYES, MP WILEY, CA TI VIRAL LOAD AND ITS RELATIONSHIP TO QUINOLINIC ACID, TNF-ALPHA, AND IL-6 LEVELS IN THE CNS OF RETROVIRAL INFECTED MICE SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE RETROVIRUS; NEUROPATHOLOGY; QUINOLINIC ACID; CYTOKINES; ANIMAL MODELS; ENVELOPE PROTEINS; TUMOR NECROSIS FACTOR; INTERLEUKIN-6; MACROPHAGES; MICROGLIA ID MURINE LEUKEMIA-VIRUS; CENTRAL-NERVOUS-SYSTEM; SPONGIFORM POLIOENCEPHALOMYELOPATHY; MUTANT; TS1; TB; PATHOGENESIS; MACROPHAGES; DISEASE; CELLS AB Mouse models of infection of the central nervous system (CNS) have been used to study retroviral-induced neurologic disease. Ecotropic-neurotropic murine leukemia virus (MuLV) infection of susceptible neonatal mice causes a neurologic disease characterized by progressive hindlimb paralysis. The lesions consist of chronic noninflammatory spongiform change predominantly involving brainstem and spinal cord. Two molecularly cloned strains of MuLV, ts-1, a temperature-sensitive mutant of Moloney MuLV, and pNE-8, derived from a feral mouse isolate Cas-Br-E, were used in this study. Infected mice were sacrificed at regular intervals postinoculation throughout the time-course of disease. The neuropathology was evaluated using standard histological and immunohistopathologic al techniques. Tissue concentrations of viral proteins and potentially cytotoxic factors were compared with the histopathology in select regions of the CNS. Areas of extensive vacuolation with neuronal and oligodendroglial infection were observed in spinal cord, brainstem, and cerebellum. High titers of infectious virus were observed within CNS lesions, whereas low titers were observed in morphologically uninvolved areas. Western blot analysis revealed abundant production of viral envelope proteins, which correlated well with infectious virus titers. Serum quinolinic acid (QUIN) concentrations in both groups of noninfected and infected mice were similar. However, CNS tissue concentrations of QUIN, TNF alpha, and IL-6 in ts-1 infected mice were significantly higher than in pNE-8 infected or noninfected mice. The difference in concentration of these factors may be the result of greater activation of macrophages/microglia in ts-1 infected mice. During murine retroviral encephalitis, CNS damage may be mediated by direct infection of CNS cells and may be enhanced by indirect effects of neurotoxic factors possibly secreted by infected/activated macrophages. C1 UNIV PITTSBURGH,PRESBYTERIAN UNIV HOSP,DIV NEUROPATHOL,PITTSBURGH,PA 15213. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90024. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-27417] NR 38 TC 22 Z9 22 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD AUG PY 1994 VL 22 IS 3 BP 143 EP 160 PG 18 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PF246 UT WOS:A1994PF24600001 PM 7993524 ER PT J AU SAVAGNER, P VALLES, AM JOUANNEAU, J YAMADA, KM THIERY, JP AF SAVAGNER, P VALLES, AM JOUANNEAU, J YAMADA, KM THIERY, JP TI ALTERNATIVE SPLICING IN FIBROBLAST GROWTH-FACTOR RECEPTOR-2 IS ASSOCIATED WITH INDUCED EPITHELIAL-MESENCHYMAL TRANSITION IN RAT BLADDER-CARCINOMA CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FACTOR FGF RECEPTOR; LIGAND-BINDING; MESSENGER-RNA; ACIDIC FGF; SIGNAL TRANSDUCTION; NERVOUS-SYSTEM; FACTOR FAMILY; K-SAM; EXPRESSION; GENES AB We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP SAVAGNER, P (reprint author), ECOLE NORMALE SUPER,PHYSIOPATHOL DEV LAB,CNRS,F-75230 PARIS 05,FRANCE. OI Yamada, Kenneth/0000-0003-1512-6805 FU NCI NIH HHS [2 R01 CA-49417-04] NR 56 TC 100 Z9 100 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG PY 1994 VL 5 IS 8 BP 851 EP 862 PG 12 WC Cell Biology SC Cell Biology GA PE827 UT WOS:A1994PE82700003 PM 7803853 ER PT J AU STRAUSS, KI JACOBOWITZ, DM SCHULKIN, J AF STRAUSS, KI JACOBOWITZ, DM SCHULKIN, J TI DIETARY CALCIUM DEFICIENCY CAUSES A REDUCTION IN CALRETININ MESSENGER-RNA IN THE SUBSTANTIA-NIGRA COMPACTA-VENTRAL TEGMENTAL AREA OF RAT-BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Note DE CALRETININ MESSENGER-RNA; RAT BRAIN; CALCIUM APPETITE; SUBSTANTIA NIGRA; VENTRAL TEGMENTAL AREA; LYSATE RNASE PROTECTION ASSAY; TYROSINE HYDROXYLASE MESSENGER-RNA ID VITAMIN-D; IMMUNOHISTOCHEMICAL LOCALIZATION; SODIUM RESTRICTION; GENE-EXPRESSION; MESSENGER-RNA; 1,25-DIHYDROXYVITAMIN-D3 AB Dietary calcium deprivation (3 weeks) affected neuronal gene expression of calretinin. Calcium deprived rats exhibited calcium appetite, weight loss, and a 28% decrease in calretinin mRNA in the substantia nigra compacta-ventral tegmental area, compared to controls. No changes were detected in 2 other mRNAs (tyrosine hydroxylase, beta-actin) and 5 other brain regions examined. This region-specific reduction of calretinin mRNA may relate to the altered physiology or behavior. C1 NIMH,BEHAV NEUROSCI LAB,BETHESDA,MD 20892. RP STRAUSS, KI (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D-48,BETHESDA,MD 20892, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1994 VL 25 IS 1-2 BP 140 EP 142 DI 10.1016/0169-328X(94)90289-5 PG 3 WC Neurosciences SC Neurosciences & Neurology GA NZ987 UT WOS:A1994NZ98700018 ER PT J AU ROSEN, JB CHUANG, E IADAROLA, MJ AF ROSEN, JB CHUANG, E IADAROLA, MJ TI DIFFERENTIAL INDUCTION OF FOS PROTEIN AND A FOS-RELATED ANTIGEN FOLLOWING ACUTE AND REPEATED COCAINE ADMINISTRATION SO MOLECULAR BRAIN RESEARCH LA English DT Note DE SENSITIZATION; STRIATUM; COCAINE; FOS ID IMMEDIATE-EARLY GENE; C-FOS; MESSENGER-RNA; EXTRACELLULAR DOPAMINE; RAT STRIATUM; NUCLEUS-ACCUMBENS; EXPRESSION; JUN; PREPRODYNORPHIN; SENSITIZATION AB The present study examined the effects of a single and five once daily injections of cocaine on the expression of c-fos mRNA, Fos protein and Fos-related antigens (Fra) in the striatum. A single injection (40 mg/kg, i.p.), which induces locomotion, increased the expression of c-fos mRNA, Fos protein and a 35 kDa Fra. In contrast, five injections (40 mg/kg, i.p.) given once a day, which induces even more behavioral stimulation, diminished the increase in c-fos mRNA and Fos protein expression. However, the cocaine-induced Fra expression was sustained and not reduced after the five injections. The results demonstrate that cocaine-induced expression of the Fos/Fra gene family is dynamic and the profile of gene transcription and translation in the striatum changes when animals are behaviorally more sensitive to cocaine. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 63 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1994 VL 25 IS 1-2 BP 168 EP 172 DI 10.1016/0169-328X(94)90295-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA NZ987 UT WOS:A1994NZ98700024 ER PT J AU PUNNONEN, K DENNING, MF RHEE, SG YUSPA, SH AF PUNNONEN, K DENNING, MF RHEE, SG YUSPA, SH TI DIFFERENCES IN THE REGULATION OF PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C IN NORMAL AND NEOPLASTIC KERATINOCYTES SO MOLECULAR CARCINOGENESIS LA English DT Article DE HA-RAS; INOSITOL PHOSPHATE; 12-O-TETRADECANOYLPHOSPHATE-13-ACETATE; TRANSFORMATION; PHOSPHOLIPASE C ID PROTEIN-KINASE-C; INOSITOL PHOSPHATE-METABOLISM; V-RAS ONCOGENE; MOUSE KERATINOCYTES; TYROSINE PHOSPHORYLATION; DIFFERENTIATION MARKERS; SIGNAL TRANSDUCTION; TERMINAL DIFFERENTIATION; MONOCLONAL-ANTIBODIES; EPIDERMAL-CELLS AB The induction of epidermal differentiation by Ca2+ in vitro is associated with enhanced activity of phosphatidylinositol-specific phospholipase C (PLC). Neoplastic keratinocyte cell lines expressing a mutant c-Ha-ras gene and normal keratinocytes transformed to the neoplastic phenotype by transduction with the v-Ha-ras gene (v-Ha-ras keratinocytes) have elevated constitutive activity of PLC that increases further in response to Ca2+, but the cells do not differentiate normally. PLC-gamma 1 (145 kDa) is the major isoform detected by immunoblotting of extracts from control, v-Ha-ras, and neoplastic keratinocyte cell lines cultured in 0.05 mM Ca2+ medium. The amount of PLC-gamma 1 protein was higher in neoplastic cell lines than in normal and v-Ha-ras keratinocytes that had similar PLC-gamma 1 protein levels. Thus, higher PLC-gamma 1 protein levels cannot account for the elevated constitutive activity PLC in v-Ha-ras keratinocytes. After induction of differentiation by Ca2+, the amount of PLC-gamma 1 protein increased in all cell types, and PLC-delta 1 (85 kDa), barely detectable in 0.05 mM Ca2+, increased. PLC-beta 1 was not detected at any Ca2+ concentration. PLC-gamma 1 and PLC-delta 1 mRNA did not increase after elevation of extracellular Ca2+, suggesting that posttranscriptional mechanisms can regulate PLC-gamma 1 and PLC-delta 1 protein levels in normal and neoplastic keratinocytes. Activation of protein kinase C by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the stimulation of inositol phosphate (InsP) formation by Ca2+ but did not alter basal InsP levels in normal keratinocytes. In contrast, TPA treatment reduced both Ca2+-stimulated and basal InsP formation in neoplastic cells lines and v-Ha-ras keratinocytes. In both normal and v-Ha-ras keratinocytes labeled with [P-32]orthophosphate, antibodies against PLC-gamma 1 immunoprecipitated a complex of P-32-labeled proteins. The relative labeling of the PLC-gamma 1 band was greater in normal than in v-Ha-ras keratinocytes. Furthermore, treatment with TPA specifically increased the relative phosphorylation of PLC-gamma 1 in v-Ha-ras keratinocytes but not in normal keratinocytes. These results suggest that the negative regulation of constitutive activity of PLC by protein kinase C differs in normal and neoplastic keratinocytes and that this could be the mechanism of increased PLC activity produced by an oncogenic ras gene in keratinocytes. (C) 1994 Wiley-Liss. Inc.* C1 NCI,CELLULAR CARCINOGENSIS,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 50 TC 8 Z9 8 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1994 VL 10 IS 4 BP 216 EP 225 DI 10.1002/mc.2940100406 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PD581 UT WOS:A1994PD58100005 PM 8068182 ER PT J AU SHIMURA, H OKAJIMA, F IKUYAMA, S SHIMURA, Y KIMURA, S SAJI, M KOHN, LD AF SHIMURA, H OKAJIMA, F IKUYAMA, S SHIMURA, Y KIMURA, S SAJI, M KOHN, LD TI THYROID-SPECIFIC EXPRESSION AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE AUTOREGULATION OF THE THYROTROPIN RECEPTOR GENE INVOLVES THYROID TRANSCRIPTION FACTOR-I SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CAMP RESPONSE ELEMENT; TISSUE-SPECIFIC EXPRESSION; DNA-BINDING SPECIFICITY; PANCREATIC-ISLET CELLS; TRANS-ACTING FACTOR; THYROGLOBULIN GENE; MESSENGER-RNA; FACTOR-I; SOMATOSTATIN EXPRESSION; 5'-FLANKING REGION AB The chimeric chloramphenicol acetyltransferase (CAT) construct, pTRCAT5'-199, containing the TSH receptor (TSHR) minimal promoter, -199 to -39 base pairs (bp), exhibits the thyroid specificity and TSH/cAMP autoregulation evident in TSHR gene expression. The present report shows that a cis-acting element between -189 and -175 bp, which binds thyroid transcription factor-1 (TTF-1), is involved in both activities. The 22 bp between -199 and -178 contains a positive element important for expression of the TSHR minimal promoter in rat FRTL-5 thyroid cells. DNAase I footprinting shows that extracts from functioning FRTL-5, but not nonfunctioning FRT thyroid or Buffalo rat liver (BRL) cells, protect a region between -189 and -175 bp. The protection is duplicated by TTF-1, and the protected element has only a two-base mismatch from the consensus TTF-1 element identified in the thyroglobulin (TG) and thyroid peroxidase minimal promoters. Gel mobility shift analyses reveal that FRTL-5 thyroid cell nuclear extracts form a specific protein/DNA complex with this region, which is prevented by the TTF-1 binding element from the TG promoter; FRT and BRL cell nuclear extracts do not have TTF-1 and do not form this complex. A role for the TSHR/TTF-1 binding element in thyroid-specific expression of the TSHR gene is evidenced as follows. Overexpression of TTF-1 in 887 or BRL cells, which have no TTF-1, increased the activity of pTRCAT5'-199, but not pTRCAT5' 177, which has no TTF-1 binding element. A nonsense mutation of the TTF1 binding element eliminated TTF-1-induced activation of TSHR promoter activity in 887 or BRL cells and reduced TSHR promoter activity in FRTL-5 thyroid cells. In contrast, mutation of this element to the TTF-1 consensus sequence of the TG or thyroid peroxidase promoter had no significant influence on TSHR promoter activity. The activity of the TSHR/ TTF-1 binding element requires a functioning cAMP response element (CRE). Thus, TTF-1 activity is lost when the CRE site is mutated to a nonfunctional, nonpalindromic sequence; it is, in contrast, maximized when CRE activity is maximized by its mutation to a consensus AP1 element. TTF-1 phosphorylation is important for binding and activity. Thus, binding of TTF-1 to the TSHR/TTF-1 element is phosphatase-sensitive and is increased by treating nuclear extracts with the catalytic subunit of protein kinase A. Overexpression of the catalytic subunit of PKA enhances TTF-1-increased activity of the TSHR minimal promoter. TSH/cAMP regulation of TTF-1 is involved in TSH/cAMP positive and negative autoregulation of the TSHR gene. Thus, within the first 2 h after TSH is given to FRTL-5 cells maintained without TSH for 7 days, TSH/cAMP increases the formation of the specific TTF-1/TSHR complex in association with increased TSHR gene expression. After 2 h, there is a decrease in TTF-1/TSHR complex formation which is coincident with TSH-induced down-regulation of TTF-1 and TSHR mRNA levels, as a function of both time and TSH concentration. The TSH-induced decrease in TTF-1 mRNA levels is duplicated by forskolin and inhibited by cycloheximide, as is the case for the ability of TSH to decrease TSHR mRNA levels. We suggest, therefore, that TSHR gene expression reflects, in part, a dynamic balance between the ability of TSH/cAMP to phosphorylate TTF-1 (positive autoregulation) and to decrease TTF-1 mRNA levels (negative autoregulation). Using oligo C from the TG promoter, we show that the TSH/cAMP biphasic regulation of TSHR gene expression is not duplicated, because TSH induces an increase in TG oligo C complex formation with another protein in the nuclear extracts, most likely Pax-8. Biphasic regulation of TSHR gene expression thus appears to reflect the specificity of the TTF-1/TSHR interaction. C1 NIDDK,DEPT BIOCHEM & METAB,CELL REGULAT SECT,BETHESDA,MD 20892. GUNMA UNIV,INST ENDOCRINOL,DEPT PHYS BIOCHEM,MAEBASHI,GUMMA 371,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Saji, Motoyasu/E-4007-2011 NR 53 TC 121 Z9 123 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1994 VL 8 IS 8 BP 1049 EP 1069 DI 10.1210/me.8.8.1049 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PB576 UT WOS:A1994PB57600009 PM 7997232 ER PT J AU JUCKER, M WALKER, LC KUO, H TIAN, M INGRAM, DK AF JUCKER, M WALKER, LC KUO, H TIAN, M INGRAM, DK TI AGE-RELATED FIBRILLAR DEPOSITS IN BRAINS OF C57BL/6 MICE - A REVIEW OF LOCALIZATION, STAINING CHARACTERISTICS, AND STRAIN SPECIFICITY SO MOLECULAR NEUROBIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Transmissible and Nontransmissible Neurodegenerative Disorders CY FEB 28-MAR 05, 1993 CL OCHO RIOS, JAMAICA SP INT BRAIN RES ORG, UNIV GOTEBORG, UNIV WEST INDIES DE AGING; AMYLOID; CORPORA AMYLACEA; TRANSGENIC MICE; SENESCENCE ACCELERATED MOUSE; GENETICS; PROTEOGLYCAN; LAMININ; ASTROCYTES; INCLUSIONS; LEARNING AND MEMORY ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; NEURITIC PLAQUES; HIGH-AFFINITY; LIFE-SPAN; MOUSE; SULFATE; PROTEOGLYCANS; LAMININ; BINDS AB The present article reviews findings regarding the age-related occurrence of clusters of unusual granules in the brains of C57BL/6 (B6) mice and discusses the potential relevance of this phenomenon as a model of specific aspects of brain aging in humans. The granules occur predominantly in the hippocampus of B6 mice and represent aggregations of fibrillar material that are mostly associated with astrocytes. The deposits become evident at about 4 to 6 mo of age, and increase markedly in both number and size thereafter. Similar structures have been observed in adult senescence accelerated mice (SAM) and have been noted, although very rarely, in older mice from other strains. The deposits appear to manifest dominant genetic heritability. Heparan sulfate proteoglycan and laminin or related molecules have been identified as components of the granular material. Although the deposits do not represent senile plaques with P-amyloid deposition, they might mimic the deposition of extracellular matrix molecules that is thought to be an early event in amyloidogenesis in the aged brain and in Alzheimer's disease. C1 NIA,GERONTOL RES CTR,MOLEC NEUROBIOL UNIT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,NEUROPATHOL LAB,BALTIMORE,MD 21205. RP JUCKER, M (reprint author), NIA,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Walker, L/J-6541-2015 OI Walker, L/0000-0001-9166-3261 NR 47 TC 23 Z9 24 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1994 VL 9 IS 1-3 BP 125 EP 133 DI 10.1007/BF02816112 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PW290 UT WOS:A1994PW29000015 PM 7534088 ER PT J AU BROWN, P MORGAN, OC MCRAE, A RODGERSJOHNSON, P AF BROWN, P MORGAN, OC MCRAE, A RODGERSJOHNSON, P TI NEURODEGENERATIVE DISEASES - CLINICAL EXPERIMENTAL, AND THERAPEUTIC APPROACHES .3. NONTRANSMISSIBLE NEURODEGENERATIVE DISORDERS - PREFACE SO MOLECULAR NEUROBIOLOGY LA English DT Editorial Material C1 UNIV W INDIES,DEPT MED,MONA,JAMAICA. GOTHENBURG UNIV,INST ANAT & CELL BIOL,GOTHENBURG,SWEDEN. UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. RP BROWN, P (reprint author), NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG-DEC PY 1994 VL 9 IS 1-3 BP U2 EP U2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA PW290 UT WOS:A1994PW29000001 ER PT J AU BENYA, RV FATHI, Z KUSUI, T PRADHAN, T BATTEY, JF JENSEN, RT AF BENYA, RV FATHI, Z KUSUI, T PRADHAN, T BATTEY, JF JENSEN, RT TI GASTRIN-RELEASING PEPTIDE RECEPTOR-INDUCED INTERNALIZATION, DOWN-REGULATION, DESENSITIZATION, AND GROWTH - POSSIBLE ROLE FOR CYCLIC-AMP SO MOLECULAR PHARMACOLOGY LA English DT Article ID SWISS 3T3 CELLS; BETA-ADRENERGIC-RECEPTOR; DEPENDENT PROTEIN-KINASE; NUCLEOTIDE-BINDING PROTEINS; PANCREATIC ACINAR-CELLS; BOMBESIN-LIKE PEPTIDES; GUINEA-PIG PANCREAS; ADENYLATE-CYCLASE; NEURITE OUTGROWTH; DISPERSED ACINI AB Stimulation of the gastrin-releasing peptide receptor (GRP-R) in Swiss 3T3 cells resembles that of a number of other recently described G protein-coupled receptors, insofar as both the phospholipase C and adenylyl cyclase signal transduction pathways are activated. GRP-R activation induces numerous alterations in both the cell and the receptor, but because two signal transduction pathways are activated it is difficult to determine the specific contributions of either pathway. We have found that BALB/3T3 fibroblasts transfected with the coding sequence for the GRP-R are pharmacologically indistinguishable from native receptor-expressing cells and activate phospholipase C in a manner similar to that of the native receptor but fail to increase cAMP in response to bombesin; thus, they may be useful cells to explore the role of activation of each pathway in altering cell and receptor function. Swiss 3T3 cells and GRP-R-transfected BALB/3T3 cells expressed identically glycosylated receptors that bound various agonists and antagonists similarly. G protein activation, as determined by evaluation of agonist-induced activation of phospholipase C and by analysis of the effect of guanosine-5'(beta,gamma-imido)triphosphate on GRP-R binding affinity, was indistinguishable. Agonist stimulation of GRP-R caused similar receptor changes (internalization and down-regulation) and homologous desensitization in both cell types. Bombesin stimulation of Swiss 3T3 cells that had been preincubated with forskolin increased cAMP levels 9-fold, but no bombesin-specific increase in cAMP levels was detected in transfected cells, even though forskolin and cholera toxin increased cAMP levels in these cells. Quiescent Swiss 3T3 cells treated with bombesin rapidly increased c-fos mRNA levels and [H-3]thymidine incorporation, whereas both effects were potentiated by forskolin. The specific protein kinase A inhibitor H-89 blocked increases in c-fos levels and [H-3]thymidine incorporation induced by low concentrations of bombesin. GRP-R-transfected BALB/3T3 cells increased c-fos mRNA levels and [H-3]thymidine incorporation with the addition of serum but not bombesin. These data suggest that bombesin-stimulated increases in cellular levels of cAMP appear not to be an important mediator of GRP-R internalization, down-regulation, or desensitization but do play an important role in bombesin-induced mitogenesis. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NR 47 TC 67 Z9 68 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 235 EP 245 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400004 PM 8078487 ER PT J AU OCARROLL, AM RAYNOR, K LOLAIT, SJ REISINE, T AF OCARROLL, AM RAYNOR, K LOLAIT, SJ REISINE, T TI CHARACTERIZATION OF CLONED HUMAN SOMATOSTATIN RECEPTOR SSTR5 SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT NEOCORTICAL NEURONS; MOLECULAR-CLONING; ADENYLYL-CYCLASE; FUNCTIONAL-CHARACTERIZATION; EXPRESSION; BRAIN; BINDING; SUBTYPE; FAMILY; IDENTIFICATION AB The recent molecular cloning of the genes encoding six distinct somatostatin (SRIF) receptor subtypes from various species has allowed for the individual expression and characterization of these receptors in mammalian cells. In the present study, we have cloned the human homologue of the SRIF receptor subtype SSTR5 (formerly termed SSTR4) and characterized its pharmacological and functional properties, as well as its distribution. Although there is 80.5% sequence homology between the cloned rat and human SSTR5 receptors, their pharmacological profiles differ. We have labeled both rat and human SSTR5, expressed in Chinese hamster ovary (CHO-K1) cells, with I-125-Tyr(11)-SRIF and performed inhibition studies using SRIF analogues of differing structures, including cyclic penta-, hexa-, and octapeptide SRIF analogues. Whereas rat SSTR5 bound compounds in all structural classes with high to moderate affinities, human SSTR5 bound most SRIF analogues with much lower affinity, with the exceptions of SRIF, SRIF-28, and L-362,855. Like rat SSTR5, human SSTR5 mediated the inhibition by SRIF of forskolin-stimulated cAMP accumulation. However, the clinically used SRIF analogue SMS 201-995, which potently inhibited cAMP formation via interaction with rat SSTR5, did not inhibit cAMP accumulation in cells expressing human SSTR5. The distribution of expression of human SSTR5 mRNA, as analyzed by reverse transcription-polymerase chain reaction, shows selective expression in small intestine, heart, adrenal, cerebellum, pituitary, placenta, and skeletal muscle but not in kidney, liver, pancreas, uterus, thymus, testis, spleen, lung, thyroid, ovary, or mammary gland. The structural differences between cloned rat and human SSTR5 receptors suggest useful strategies for identifying regions of this receptor subtype that may be involved in ligand binding specificities. Identification of subtype-selective SRIF analogues may lead to more specific pharmacological therapeutic interventions. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. FU NIMH NIH HHS [MH45533, MH48518] NR 37 TC 108 Z9 109 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 291 EP 298 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400010 PM 8078491 ER PT J AU MORRIS, DI GREENBERGER, LM BRUGGEMANN, EP CARDARELLI, C GOTTESMAN, MM PASTAN, I SEAMON, KB AF MORRIS, DI GREENBERGER, LM BRUGGEMANN, EP CARDARELLI, C GOTTESMAN, MM PASTAN, I SEAMON, KB TI LOCALIZATION OF THE FORSKOLIN LABELING SITES TO BOTH HALVES OF P-GLYCOPROTEIN - SIMILARITY OF THE SITES LABELED BY FORSKOLIN AND PRAZOSIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG-RESISTANT CELLS; BACTERIAL TRANSPORT PROTEINS; MEMBRANE GLYCOPROTEIN; PHOTOACTIVE ANALOGS; CHEMICAL-PROPERTIES; FUNCTIONAL-ANALYSIS; GLUCOSE-TRANSPORT; ADENYLATE-CYCLASE; BINDING-SITE; MOUSE MDR1 AB An iodinated derivative of forskolin, 6-O-[[2-[3-(4-azido-3-[I-125]iodophenyl)propionamido]ethyl]carbamyl]forskolin ([I-125]6-AIPP-Fsk), photolabels the multidrug efflux pump P-glycoprotein in membranes prepared from the multidrug-resistant cell lines KB-V1 and KB-C1. The labeling site for [I-125]6-AIPP-Fsk was localized by immunoprecipitation of tryptic fragments of P-glycoprotein labeled in KB-C1 membranes. A 6-kDa, photolabeled, tryptic fragment was immunoprecipitated by antiserum raised against residues 348-419 of P-glycoprotein, PEPG9, but not by antisera raised against flanking regions PEPG7 and PEPG11. A peptide that corresponds to residues 343-359 of P-glycoprotein inhibited immunoprecipitation of the 6-kDa fragment by antiserum against PEPG9 but had no effect on the immunoprecipitation of photolabeled fragments by antiserum against PEPG7. A second peptide, corresponding to residues 360-376, had no effect on the immunoprecipitation by antiserum against PEPG9. [I-125]6-AIPP-Fsk labels the carboxyl-terminal half of P-glycoprotein, because low molecular mass tryptic fragments were immunoprecipitated by three carboxyl-terminal antisera. Therefore, [I-125]6-AlPP-Fsk labels both halves of P-glycoprotein, and labeling in the aminoterminal half can be localized to residues 291-359, which span proposed transmembrane regions 5 and 6. KB-V1 membranes photolabeled with [I-125]6-AIPP-Fsk and [I-125]iodoarylazidoprazosin were digested with either Staphlyococcus aureus V8 protease or chymotrypsin and had similar digestion patterns, suggesting that the two drugs label the same sites on P-glycoprotein. C1 US FDA,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. NICHHD,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 52 TC 98 Z9 98 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 329 EP 337 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400014 PM 7915819 ER PT J AU KAZANIETZ, MG LEWIN, NE GAO, F PETTIT, GR BLUMBERG, PM AF KAZANIETZ, MG LEWIN, NE GAO, F PETTIT, GR BLUMBERG, PM TI BINDING OF [26-H-3]BRYOSTATIN-1 AND ANALOGS TO CALCIUM-DEPENDENT AND CALCIUM-INDEPENDENT PROTEIN-KINASE-C ISOZYMES SO MOLECULAR PHARMACOLOGY LA English DT Article ID PHORBOL ESTER PHARMACOPHORE; TUMOR PROMOTERS; BRYOSTATIN-1; RECEPTOR; CELLS; PURIFICATION; EXPRESSION AB In this study we explored the pattern of protein kinase C (PKC) isozyme selectivity of the bryostatins, a unique class of PKC activators that induce only a subset of the typical phorbol ester responses and antagonize those phorbol ester-mediated responses that they themselves fail to induce. The binding properties of individual recombinant PKC isozymes that had been expressed in insect cells, isolated, and reconstituted in Triton X-100/phosphatidylserine mixed micelles were determined. [H-3] Bryostatin 1 showed lower affinity for PKC-beta(1) and -gamma, compared with PKC-alpha, -delta, -epsilon, and -eta. This pattern contrasts with that observed for other PKC ligands. These latter assays were conducted with isozymes reconstituted in phosphatidylserine, conditions that unfortunately do not permit quantitation of bryostatin 1 binding under equilibrium conditions. Using Delta(19,20)-bryostatin 10 and Delta(19,20)-isobryostatin 10, we could distinguish the respective roles of ligand and lipid in the pattern of selectivity. When isozymes were reconstituted in phosphatidylserine vesicles, Delta(19,20)-bryostatin 10 and Delta(19,20)-isobryostatin 10 showed similar affinities for PKC-alpha and -gamma, similarly to the phorbol esters. However, in the mixed micellar system, PKC-gamma showed a significantly lower binding affinity, as had been observed for bryostatin 1. These results suggest that the unique pattern of biological responses to the bryostatins does not represent a unique pattern of isotype recognition. Furthermore, the lipid environment of PKC plays an important role in determining the binding selectivity for individual isozymes. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. NR 22 TC 56 Z9 56 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 374 EP 379 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400020 PM 8078499 ER PT J AU CHAMULITRAT, W JORDAN, SJ MASON, RP AF CHAMULITRAT, W JORDAN, SJ MASON, RP TI NITRIC-OXIDE PRODUCTION DURING ENDOTOXIC-SHOCK IN CARBON TETRACHLORIDE-TREATED RATS SO MOLECULAR PHARMACOLOGY LA English DT Article ID KUPFFER CELLS; L-ARGININE; PROTEIN-SYNTHESIS; LIVER-INJURY; INVIVO; CYTOCHROME-P-450; HEPATOTOXICITY; INHIBITION; RESONANCE; MECHANISM AB Earlier studies showed that hepatotoxicant-treated experimental animals were more susceptible than controls to the lethal effects of bacterial endotoxin. The exact mechanisms of this effect were not understood. In this paper we showed that nitric oxide ((NO)-N-.) was produced in whole blood and in liver tissues of rats that had been treated with a nonlethal dose of CCl4 (1.3 g/kg) followed by a low dose of lipopolysaccharide (LPS) (100 mu g/kg). EPR spectroscopy was used in this study to detect nitrosyl-protein complexes. Hemoglobin-nitrosyl complexes were detected in both whole blood and liver. By performing analyses of EPR spectra obtained from hepatocytes exposed to (NO)-N-., we were able to identify EPR signals attributable to nitrosyl-cytochrome P420 in rat liver. We found that nitrosyl complex formation in red blood cells and liver was inhibited by treatment with N-G-monomethyl-L-arginine, suggesting enzymatic biosynthesis of (NO)-N-.. A small but significant inhibition of nitrosyl complex formation by gadolinium trichloride pretreatment was found in the liver, suggesting that Kupffer cells were also involved in (NO)-N-. biosynthesis, because this treatment decreased Kupffer cells. There was a synergistic effect of CCl4 and LPS on the serum levels of the hepatic enzymes aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and sorbitol dehydrogenase, which are indices of parenchymal cell damage. NG-Monomethyl-L-arginine treatment increased these hepatic enzyme activities, suggesting a protective role for (NO)-N-.. EPR resonances at g similar to 2.48, 2.29, and 1.91, due to low-spin cytochromes P450/ P420 (Fe3+), were decreased in the livers of LPS-induced rats that had been previously treated with CCl4, indicating cytochrome P450/P420 destruction or at least a change in the valence state of the cytochrome P450/P420 heme groups to Fe2+ in the presence of (NO)-N-.. Because nitrosyl-cytochrome P450 is not stable, the concomitant detection of nitrosyl-cytochrome P420 (Fe2+) could account, at least in part, for the decrease of the ferric low-spin heme groups. Our novel observations of hepatic nitrosyl species suggest that (NO)-N-. plays an important role during hepatic injury caused by CCl4 in hosts exposed to endotoxin. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 46 TC 48 Z9 48 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1994 VL 46 IS 2 BP 391 EP 397 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE364 UT WOS:A1994PE36400023 PM 8078502 ER PT J AU EDRIS, W BURGETT, B STINE, OC FILBURN, CR AF EDRIS, W BURGETT, B STINE, OC FILBURN, CR TI DETECTION AND QUANTITATION BY COMPETITIVE PCR OF AN AGE-ASSOCIATED INCREASE IN A 4.8-KB DELETION IN RAT MITOCHONDRIAL-DNA SO MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING LA English DT Article DE MITOCHONDRIAL DNA DAMAGE; MITOCHONDRIAL DNA DELETIONS; COMPETITIVE PCR; ANIMAL MODEL OF DELETIONS; MITOCHONDRIAL DNA AND AGING ID CYTOCHROME-C-OXIDASE; KEARNS-SAYRE SYNDROME; DEGENERATIVE DISEASES; SKELETAL-MUSCLE; HUMAN BRAIN; HUMAN-HEART; MUTATION; TISSUES; GENOMES; DAMAGE AB Recent studies on human tissues have shown that the guantity of partially deleted mitochondrial DNA (mtDNA) increases with age. In this study, mtDNAs from the livers of young adult and old Wistar rats were analyzed by PCR. Evidence for partially deleted mtDNAs was found, with a 4834-bp deletion present in all animals and most easily detected in samples from senescent rats. The deletion breakpoint occurs at a 16-bp direct repeat present in the cytochrome oxidase I and ATPase 6 genes. This deletion in rats is similar in size and location to the 5.0-kb deletion observed in human mtDNA. The proportion of rat mtDNA with this 4.8-kb deletion was quantitated by a competitive PCR assay. The ratio of partially deleted mtDNA/total mtDNA in liver mtDNA from individual 6 month old rats ranged from 5 X 10(-6) to 3 X 10(-5), while the ratio in 24 month old rats ranged from 8 X 10(-4) to 5 X 10(-3), with a mean 100-fold increase with age. These increases are in the range observed for human mtDNA during aging. Thus senescent rats can be used as a model to study this type of mitochondrial DNA damage in aging. The method and reagents described should prove useful in studies of the mechanism(s) underlying deletions, their significance to the aging process, and testing of various compounds or interventions for their ability to slow the process. C1 NIA,GERONTOL RES CTR,BIOL SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. NR 46 TC 68 Z9 70 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8734 J9 MUTAT RES-DNAGING G JI Mutat. Res. DNAging Genet. Instabil. Aging PD AUG PY 1994 VL 316 IS 2 BP 69 EP 78 DI 10.1016/0921-8734(94)90009-4 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PM078 UT WOS:A1994PM07800002 PM 7521004 ER PT J AU MCFEE, AF ABBOTT, MG GULATI, DK SHELBY, MD AF MCFEE, AF ABBOTT, MG GULATI, DK SHELBY, MD TI RESULTS OF MOUSE BONE-MARROW MICRONUCLEUS STUDIES ON 1,4-DIOXANE SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Note DE 1,4-DIOXANE; MOUSE; BONE MARROW; CLASTOGENICITY; MICRONUCLEI ID SALMONELLA MUTAGENICITY; CHEMICAL-STRUCTURE; CARCINOGENICITY; RODENTS C1 ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. NIEHS,RES TRIANGLE PK,NC 27709. RP MCFEE, AF (reprint author), OAK RIDGE INST SCI EDUC,DIV MED SCI,POB 117,OAK RIDGE,TN 37831, USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD AUG PY 1994 VL 322 IS 2 BP 145 EP 148 DI 10.1016/0165-1218(94)90096-5 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PM070 UT WOS:A1994PM07000010 PM 7519323 ER PT J AU KUNZ, BA KOHALMI, SE KUNKEL, TA MATHEWS, CK MCINTOSH, EM REIDY, JA AF KUNZ, BA KOHALMI, SE KUNKEL, TA MATHEWS, CK MCINTOSH, EM REIDY, JA TI DEOXYRIBONUCLEOSIDE TRIPHOSPHATE LEVELS - A CRITICAL FACTOR IN THE MAINTENANCE OF GENETIC STABILITY SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Review DE DEOXYRIBONUCLEOSIDE TRIPHOSPHATE; GENETIC STABILITY ID HAMSTER OVARY CELLS; SISTER-CHROMATID EXCHANGES; COMMON FRAGILE SITES; DNA PRECURSOR POOL; MOUSE FM3A CELLS; THYMINE NUCLEOTIDE DEPLETION; RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; IMMUNODEFICIENCY-VIRUS COMPOUND; CANCER CHEMOTHERAPEUTIC-AGENTS; YEAST SACCHAROMYCES-CEREVISIAE AB DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases. C1 NATL RES COUNCIL CANADA,INST PLANT BIOTECHNOL,SASKATOON S7N 0W9,SK,CANADA. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. YORK UNIV,DEPT BIOL,N YORK M3J 1P3,ON,CANADA. CTR DIS CONTROL & PREVENT,NATL CTR ENVIRONM HLTH,MOLEC BIOL BRANCH,ATLANTA,GA 30341. RP KUNZ, BA (reprint author), UNIV MANITOBA,DEPT MICROBIOL,WINNIPEG R3T 2N2,MB,CANADA. NR 513 TC 155 Z9 158 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1110 J9 MUTAT RES-REV GENET JI Mutat. Res.-Rev. Genet. Toxicol. PD AUG PY 1994 VL 318 IS 1 BP 1 EP 64 DI 10.1016/0165-1110(94)90006-X PG 64 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PM073 UT WOS:A1994PM07300001 PM 7519315 ER PT J AU ALBERTSEN, HM SMITH, SA MAZOYER, S FUJIMOTO, E STEVENS, J WILLIAMS, B RODRIGUEZ, P CROPP, CS SLIJEPCEVIC, P CARLSON, M ROBERTSON, M BRADLEY, P LAWRENCE, E HARRINGTON, T SHENG, ZM HOOPES, R STERNBERG, N BROTHMAN, A CALLAHAN, R PONDER, BAJ WHITE, R AF ALBERTSEN, HM SMITH, SA MAZOYER, S FUJIMOTO, E STEVENS, J WILLIAMS, B RODRIGUEZ, P CROPP, CS SLIJEPCEVIC, P CARLSON, M ROBERTSON, M BRADLEY, P LAWRENCE, E HARRINGTON, T SHENG, ZM HOOPES, R STERNBERG, N BROTHMAN, A CALLAHAN, R PONDER, BAJ WHITE, R TI A PHYSICAL MAP AND CANDIDATE GENES IN THE BRCA1 REGION ON CHROMOSOME 17Q12-21 SO NATURE GENETICS LA English DT Article ID BREAST-OVARIAN-CANCER; POLYMERASE CHAIN-REACTION; FAMILIAL BREAST; YEAST; DNA; CLONING; SEQUENCES; LIBRARY; CDNA; PCR AB We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1. C1 UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1QP,ENGLAND. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880. RP ALBERTSEN, HM (reprint author), UNIV UTAH,ECCLES INST HUMAN GENET,SALT LAKE CITY,UT 84112, USA. FU NHGRI NIH HHS [R01-HG00339, R01-HG00367-04] NR 40 TC 88 Z9 91 U1 1 U2 13 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1994 VL 7 IS 4 BP 472 EP 479 DI 10.1038/ng0894-472 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PA832 UT WOS:A1994PA83200012 PM 7951316 ER PT J AU BHAT, TN BALDWIN, ET LIU, BS CHENG, YSE ERICKSON, JW AF BHAT, TN BALDWIN, ET LIU, BS CHENG, YSE ERICKSON, JW TI CRYSTAL-STRUCTURE OF A TETHERED DIMER OF HIV-1 PROTEINASE COMPLEXED WITH AND INHIBITOR SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROTEASE AB HIV-1 proteinase (HIV PR) is a dimeric enzyme composed of two identical polypeptide chains that associate with twofold symmetry. We have determined to 1.8 Angstrom the crystal structure of a covalently tethered dimer of HIV PR. The tethered dimer:inhibitor complex is identical in nearly every respect to the complex of the same inhibitor with the wild type dimeric molecule, except for the linker region, Our results suggest that the tethered dimer may be a useful surrogate enzyme for Studying the effects of single site mutations on Substrate and inhibitor binding as well as on enzyme asymmetry, and for simulating independent mutational drift of the two domains which has been Proposed to have led to the evolution of modern day, single-chain aspartic proteinases. C1 NCI, FREDERICK CANC RES & DEV CTR, FREDERICK BIOMED SUPERCOMP CTR, PRI DYNCORP, FREDERICK, MD 21702 USA. DUPONT MERCK PHARMACEUT CO, WILMINGTON, DE 19880 USA. NR 18 TC 32 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD AUG PY 1994 VL 1 IS 8 BP 552 EP 556 DI 10.1038/nsb0894-552 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QR967 UT WOS:A1994QR96700017 PM 7664084 ER PT J AU MERCHENTHALER, I AF MERCHENTHALER, I TI INDUCTION OF ENKEPHALIN IN TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS OF PREGNANT, PSEUDOPREGNANT, LACTATING AND AGED FEMALE RATS SO NEUROENDOCRINOLOGY LA English DT Article DE ARCUATE NUCLEUS; DOUBLE LABELING; HYPOTHALAMUS; IMMUNOCYTOCHEMISTRY; IN SITU HYBRIDIZATION; PROLACTIN; OPIATE PEPTIDES ID CENTRAL-NERVOUS-SYSTEM; TYROSINE-HYDROXYLASE; MEDIAN-EMINENCE; PROLACTIN; BRAIN; HYPOTHALAMUS; TURNOVER; PEPTIDES; MORPHINE; LOCALIZATION AB The tuberoinfundibular dopaminergic (TIDA) neurons projecting to the external zone of the median eminence arise in the dorsomedial and ventrolateral subdivisions of the arcuate nucleus. In cycling female rates these regoins contain only scattered enkephalin-immunoreactive (ENK-i) neurons some of which coexpress dopamine, detected by immunostaining for tyrosine hydroxylase (TH). The present immunocytochemical, in situ hybridization and retrograde-labeling studies show that each TIDA neuron of pregnant, pseudopregnant, lactating, and aged female rats contains ENK-like immunoreactivity and pro-ENK mRNA and projects to the hypophysial portal circulation. Ovariectomy of lactating and aged rats did not change ENK staining within TIDA neurons, suggesting that ovarian steroids do not play a critical role in the colocalization of ENK and dopamine. Since prolactin levels are elevated in each of these experimental animals, a possible role for prolactin in the induction of the ENK gene in TIDA neurons is suggested. Prolactin stimulates dopamine and its own secretion via a short-loop feedback mechanism. The sensitivity of this regulatory mechanism is altered in these experimental animals, resulting in elevated prolactin secretion. ENK, which has prolactin-releasing activity and is colocalized with dopamine, could mediate the positive short-loop feedback regulation and sustain elevated levels of prolactin in pregnant, pseudopregnant, lactating, and aged animals. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 23 Z9 23 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD AUG PY 1994 VL 60 IS 2 BP 185 EP 193 DI 10.1159/000126750 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA NZ447 UT WOS:A1994NZ44700010 PM 7969776 ER PT J AU HERNING, RI GLOVER, BJ KOEPPL, B PHILLIPS, RL LONDON, ED AF HERNING, RI GLOVER, BJ KOEPPL, B PHILLIPS, RL LONDON, ED TI COCAINE-INDUCED INCREASES IN EEG-ALPHA AND EEG-BETA ACTIVITY - EVIDENCE FOR REDUCED CORTICAL PROCESSING SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE COCAINE; EEG; DRUG ABUSE ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; NORMAL VOLUNTEERS; BLOOD-FLOW; LIDOCAINE; HUMANS; AMPHETAMINE; DIAZEPAM AB To understand the effects of cocaine on the cerebral cortex, 14 male polydrug abusers were enrolled in a study on the effects of cocaine on the electroencephalogram (EEG). The experimental treatments were placebo, 20 mg cocaine or 40 mg cocaine IV administered in a double-blind, pseudorandom design. The EEG was recorded from 13 electrode positions over the left hemisphere during a 3-minute baseline recording and for 30 minutes after initiation of the IV injection. The spectral power for delta, theta, alpha and beta EEG bands was calculated from data collected in each 3-minute interval. Cocaine significantly increased beta in frontal and central areas and enhanced alpha in frontal and temporal regions. Cocaine-induced increases in EEG beta power had a cortical distribution similar to those produced try barbiturates and benzodiazepines. As all of these drugs reduce cortical glucose metabolism, the increases in beta power may reflect a reduction in cortical neural activity. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. RP HERNING, RI (reprint author), NIDA,ADDICT RES CTR,MED AFFAIRS BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 37 TC 30 Z9 30 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1994 VL 11 IS 1 BP 1 EP 9 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PC574 UT WOS:A1994PC57400001 PM 7945738 ER PT J AU BREWERTON, TD MURPHY, DL JIMERSON, DC AF BREWERTON, TD MURPHY, DL JIMERSON, DC TI TESTMEAL RESPONSES FOLLOWING M-CHLOROPHENYLPIPERAZINE AND L-TRYPTOPHAN IN BULIMICS AND CONTROLS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID FOOD-INTAKE; EATING DISORDERS; BRAIN-SEROTONIN; HYPOTHALAMIC SEROTONIN; SATIETY RESPONSES; FEEDING-BEHAVIOR; 5-HT1C RECEPTORS; RATS; CONSUMPTION; NERVOSA AB A wealth of data support a role for serotonin (5-HT) function in the mediation of satiety responses, that are impaired in patients with bulimia nervosa. Testmeal results are presented in which 26 bulimic patients and 17 normal controls were given in randomized, double-blind-fashion, placebo, and the 5-HT agents m-chlorophenylpiperazine (m-CPP, 0.5 mg/kg p.o.) and L-tryptophan (L-TRP, 100 mg/kg I. V.). Three and one-half hours after drug administration, subjects were allowed to eat and lib from a standardized testmeal of 3,500 calories, after which postprandial vomiting was not allowed. M-CPP, but not L-TRP, significantly decreased meal size in the combined group, the controls, and to a lesser extent, the bulimics (p less than or equal to .06). Maximum m-CPP concentrations were inversely correlated to the number of calories consumed in the fetal group. Following m-CPP, there were significant decreases in carbohydrate, protein, and fat intake in the total group of subjects. There were also trends for decreased carbohydrate and protein intake in the bulimics following m-CPP. There were trends for both m-CPP and L-TRP to reduce fat intake in the controls. Differences in the effects between m-CPP and L-TRP are likely due to differential involvement of 5-HT receptor subtypes at presynaptic and postsynaptic sites. These studies in humans confirm reports in animals that m-CPP decreases food intake, including carbohydrates, protein, and fat in a mixed testmeal. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. BETH ISRAEL HOSP,DEPT PSYCHIAT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. RP BREWERTON, TD (reprint author), MED UNIV S CAROLINA,INST PSYCHIAT,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 77 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1994 VL 11 IS 1 BP 63 EP 71 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PC574 UT WOS:A1994PC57400008 PM 7945745 ER PT J AU BRAUN, AR CARSON, RE ADAMS, HR FINN, RD FRANCIS, BE HERSCOVITCH, P AF BRAUN, AR CARSON, RE ADAMS, HR FINN, RD FRANCIS, BE HERSCOVITCH, P TI A KINETIC COMPARISON OF [F-18] 2-FLUORO-2-DEOXYGLUCOSE AND [F-18] 2-FLUORO-2-DEOXYMANNOSE USING POSITRON EMISSION TOMOGRAPHY SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID CEREBRAL GLUCOSE-UTILIZATION; METABOLIC-RATE; CONSTANTS; HUMANS; MODEL AB Rate constants and fractional metabolic rates were estimated for the stereoisomers [F-18]2-fluoro-2-deoxyglucose (FDG) and [F-18]2-fluoro-2-deoxymannose (FDM) in 5 male baboons using positron emission tomography. Each animal, serving as its own control, was injected with both compounds under controlled physiological conditions. Results indicate that there is a 20% reduction in apparent cerebral metabolic rates for glucose when FDM is used as the analogue. This suggests that as supplies of O-18 become depleted, the presence of FDM as an impurity should warrant consideration in the choice of alternatives to no-carrier-added FDG synthesis. C1 NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,DEPT RADIOL & MED PHYS,NEW YORK,NY. MERCK SHARP & DOHME LTD,W POINT,PA. RP BRAUN, AR (reprint author), NIDCD,VSLB,VSS,BLDG 10,ROOM 5D38,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 13 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 1994 VL 21 IS 6 BP 857 EP 863 DI 10.1016/0969-8051(94)90165-1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD516 UT WOS:A1994PD51600008 PM 9234335 ER PT J AU JOHNSON, ES AF JOHNSON, ES TI CANCER MORTALITY AMONG WORKERS IN THE MEAT DEPARTMENT OF SUPERMARKETS SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LUNG-CANCER; BUTCHERS; INDUSTRY; CARCINOGENICITY; BENZENE; RISK; TOXICOLOGY; INSTITUTE; LEUKEMIA; COHORT AB Objectives-The aim was to study the risk of dying from cancer among workers in the meat department of supermarkets potentially exposed to oncogenic retroviruses and fumes during the wrapping and labelling of meat. Methods-Cancer mortality for the period 1949 to 1989 was compared in a previously studied cohort of 10 841 members of a local meatcutters' union in Baltimore, Maryland who worked in the meat department of supermarkets, after an extended follow up of nine years (1981-9). Person-years and deaths were apportioned in five-year intervals by sex, age, and calendar year, and standardised mortality ratio (SMR) and proportional mortality ratio (PMR) analyses were conducted. The United States general population was used as the comparison group. Analyses of SMR and PMR were also conducted for a control group of workers from the same union who worked exclusively in non-meat companies. Results and discussion-Among women, an SMR of 1.6 (95% confidence interval (95% CI) 1.1-2.2) and a PMR of 1.5 (95% CI 1.0-2.0) for lung cancer were found. For men, the SMR for cancer of the buccal cavity and pharynx was 1.8 (95% CI 1.0-3.0), and for colon cancer it was 1.5 (95% CI 1.1-2.1). The respective PMRs were 1.9 (95% CI 1.1-3.1) and 1.5 (95% Cl 1.1-2.1). Whereas the role of non-occupational factors needs to be taken into account before occupational factors can be implicated in the occurrence of the excess of cancer of the buccal cavity and pharynx, and colon cancer in men, there is reason to suspect that occupational factors may be responsible for the lung cancer excess in women. Thus exposures that occur predominantly in women, such as exposure to fumes during wrapping and labelling, should be investigated as to their role in this excess. C1 NIEHS,EPIDEMIOL BRANCH,ENVIRONM & MOLEC EPIDEMIOL SECT,RES TRIANGLE PK,NC 27709. NR 52 TC 22 Z9 23 U1 0 U2 0 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 AUG PY 1994 VL 51 IS 8 BP 541 EP 547 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PA877 UT WOS:A1994PA87700007 PM 7951779 ER PT J AU HNIZDO, E SLUISCREMER, GK BASKIND, E MURRAY, J AF HNIZDO, E SLUISCREMER, GK BASKIND, E MURRAY, J TI EMPHYSEMA AND AIRWAY-OBSTRUCTION IN NONSMOKING SOUTH-AFRICAN GOLD MINERS WITH LONG EXPOSURE TO SILICA DUST SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LUNG-FUNCTION; MORTALITY AB Objective Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. Methods-242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. Results-The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. Conclusion-The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease. C1 MED BUR OCCUPAT DIS,EPIDEMIOL RES UNIT,JOHANNESBURG 2000,SOUTH AFRICA. NATL CTR OCCUPAT HLTH,BRAAMFONTEIN 2017,SOUTH AFRICA. RP HNIZDO, E (reprint author), NIEHS,EPIDEMIOL BRANCH,MD A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 30 Z9 32 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 AUG PY 1994 VL 51 IS 8 BP 557 EP 563 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PA877 UT WOS:A1994PA87700010 PM 7951782 ER PT J AU CLEVELAND, JL TROPPMAIR, J PACKHAM, G ASKEW, DS LLOYD, P GONZALEZGARCIA, M NUNEZ, G IHLE, JN RAPP, UR AF CLEVELAND, JL TROPPMAIR, J PACKHAM, G ASKEW, DS LLOYD, P GONZALEZGARCIA, M NUNEZ, G IHLE, JN RAPP, UR TI V-RAF SUPPRESSES APOPTOSIS AND PROMOTES GROWTH OF INTERLEUKIN-3-DEPENDENT MYELOID CELLS SO ONCOGENE LA English DT Article ID RECOMBINANT MURINE RETROVIRUS; C-MYC; HEMATOPOIETIC-CELLS; BCL-2 ONCOPROTEIN; KINASE-ACTIVITY; PROTEIN-KINASE; BONE-MARROW; B-CELLS; EXPRESSION; ACTIVATION AB Interleukin-3 (IL-3) is required for the proliferation, survival and differentiation of myeloid progenitors. In the absence of IL-3, murine myeloid 32D.3 cells accumulate in the G1 phase of the cell cycle and subsequently undergo programmed cell, death, or apoptosis. Here we demonstrate that enforced expression of the v-raf oncogene suppresses apoptosis of myeloid 32D.3 cells following the withdrawal of IL-3. Surprisingly, steady state levels of Bcl-2, an oncogene known to suppress apoptosis, were not dependent upon IL-3 in 32D.3 cells and its levels were not augmented in v-raf clones. This suggests that ability of v-raf to suppress apoptosis in the absence of ligand is either Bcl-2 independent or that v-raf kinase promotes Bcl-2 function. v-raf also promoted growth of these cells in the presence of IL-3. v-raf clones proliferated at an increased rate due to a shortened G1 phase and had decreased requirements for IL-3 for growth. Therefore, transformation of myeloid cells by v-raf involves signaling pathways which promote both cell cycle progression and cell survival. C1 UNIV TENNESSEE, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. NCI, FREDERICK CANC RES FACIL, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA. RP CLEVELAND, JL (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [P0 CA21765]; NIDDK NIH HHS [DK42932, DK44158] NR 61 TC 122 Z9 122 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1994 VL 9 IS 8 BP 2217 EP 2226 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NX629 UT WOS:A1994NX62900013 PM 8036007 ER PT J AU MAHANTY, S AF MAHANTY, S TI FEBRILE ILLNESS CAUSED BY PARASITES SO PEDIATRIC ANNALS LA English DT Article RP MAHANTY, S (reprint author), NIAID,PARASIT DIS LAB,CLIN PARASITOL SECT,BLDG 4,RM 126,BETHESDA,MD 20892, USA. OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD AUG PY 1994 VL 23 IS 8 BP 398 EP & PG 0 WC Pediatrics SC Pediatrics GA PC293 UT WOS:A1994PC29300003 PM 7808814 ER PT J AU MAWHORTER, SD AF MAWHORTER, SD TI EOSINOPHILIA CAUSED BY PARASITES SO PEDIATRIC ANNALS LA English DT Article RP MAWHORTER, SD (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 8 Z9 9 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD AUG PY 1994 VL 23 IS 8 BP 405 EP & PG 0 WC Pediatrics SC Pediatrics GA PC293 UT WOS:A1994PC29300004 PM 7808815 ER PT J AU KENNEY, RT AF KENNEY, RT TI PARASITIC CAUSES OF DIARRHEA SO PEDIATRIC ANNALS LA English DT Article RP KENNEY, RT (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD AUG PY 1994 VL 23 IS 8 BP 414 EP & PG 0 WC Pediatrics SC Pediatrics GA PC293 UT WOS:A1994PC29300005 PM 7808816 ER PT J AU NELSON, DL KURMAN, CC AF NELSON, DL KURMAN, CC TI MOLECULAR-GENETIC ANALYSIS OF THE PRIMARY IMMUNODEFICIENCY DISORDERS SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; CD40 LIGAND; HYPER-IGM; EXPRESSION; RECEPTOR; CARRIER; CELLS RP NELSON, DL (reprint author), NCI,METAB BRANCH,IMMUNOPHYSIOL SECT,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 23 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 1994 VL 41 IS 4 BP 657 EP 664 PG 8 WC Pediatrics SC Pediatrics GA PA771 UT WOS:A1994PA77100005 PM 7914021 ER PT J AU MCCASLIN, RI PIKIS, A RODRIGUEZ, WJ AF MCCASLIN, RI PIKIS, A RODRIGUEZ, WJ TI PEDIATRIC PLASMODIUM-FALCIPARUM MALARIA - A 10-YEAR EXPERIENCE FROM WASHINGTON, DC SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE MALARIA; ANTIMALARIAL THERAPY ID CEREBRAL MALARIA; EXCHANGE-TRANSFUSION; AMERICAN TRAVELERS; UNITED-STATES; DOUBLE-BLIND; CHILDREN; PREVENTION; CHEMOPROPHYLAXIS; PROPHYLAXIS; QUINIDINE AB From 1983 to 1992 a total of 64 children were admitted with a diagnosis of malaria to Children's National Medical Center in Washington, DC. Specific etiology is available in 59 of 64. Of these 59 cases 52 (88%) were caused by Plasmodium falciparum. Fifty-one of 52 infections were acquired in Africa, 35 (67%) of these in traveling United States citizens. Eleven (21%) of 52 children were initially admitted to the Intensive Care Unit for iv quinidine or quinine therapy. Eight (73%) of these 11 patients compared with 12 (29%) of 41 general ward admissions had been misdiagnosed within 10 days before admission (P = 0.012). Five of 11 Intensive Care Unit patients underwent exchange transfusion. One child died and one was left with severe neurologic deficit. Malaria must be considered in the differential diagnosis for any febrile child who has traveled to or from a malarious area within the previous 12 months. Delayed diagnosis of pediatric Plasmodium falciparum malaria is associated with an increased severity of illness. Because of the frequency of international travel, United States physicians will need to be familiar with the presentation and management of imported P. falciparum malaria. C1 CHILDRENS NATL MED CTR,DIV INFECT DIS,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,CTR EMERGENCY MED TRAUMA,WASHINGTON,DC 20010. NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NR 51 TC 44 Z9 44 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD AUG PY 1994 VL 13 IS 8 BP 709 EP 715 DI 10.1097/00006454-199408000-00006 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA PC291 UT WOS:A1994PC29100006 PM 7970971 ER PT J AU RIDDICK, L CHROUSOS, GP JEFFRIES, S PANG, SY AF RIDDICK, L CHROUSOS, GP JEFFRIES, S PANG, SY TI COMPARISON OF ADRENOCORTICOTROPIN AND ADRENAL-STEROID RESPONSES TO CORTICOTROPIN-RELEASING HORMONE VERSUS METYRAPONE TESTING IN PATIENTS WITH HYPOPITUITARISM SO PEDIATRIC RESEARCH LA English DT Article ID PLASMA ADRENOCORTICOTROPIN; CUSHINGS-SYNDROME; STIMULATION TEST; 3-ALPHA-ANDROSTANEDIOL GLUCURONIDE; CORTISOL RESPONSES; PITUITARY; OVINE; INSUFFICIENCY; HYPERPLASIA; DISORDERS AB We compared the responses of ACTH and cortisol (F) to corticotropin-releasing hormone (CRH) administration (ovine 1 mu g/kg i.v. bolus) with the responses of urinary 17-OH corticosteroids (17-OHCS) and serum deoxycorticosterone (DOC) to metyrapone administration (450 mg/ m(2)/dose every 4 h x seven doses) in 16 hypopituitary patients. Glucocorticoid therapy for these patients was withheld for a minimum of 3 wk before testing. The CRH test was performed 3 d before or 3 wk after the metyrapone test was used to diagnose the ACTH reserve status. In nine ACTH-intact hypopituitary patients (postmetyrapone 17-OHCS > 12.2 mu mol/m(2)/d; DOC greater than or equal to 11.5 nmol/L), the peak F (497-773 nmol/L) and ACTH (5.2-22 pmol/L) responses to CRH stimulation were similar to those of normal subjects (F peak = 554-993 nmol/L and ACTH peak = 6-25 pmol/L at 15-60 min). In one patient with partial ACTH deficiency (postmetyrapone 17-OHCS = 10.5 mu mol/m(2)/d; DOC = 6 nmol/L), the peak F response was low and delayed (246 nmol/L at 180 min) and the peak ACTH response was normal (7 pmol/L). Six severely ACTH-deficient patients (postmetyrapone 17OHCS< 5.4 mu mol/m(2)/d; DOC less than or equal to 3.4 nmol/L) had a low F response at 15-90 min in all, with a delayed rise in three at 120-180 min in response to CRH administration, where as ACTH responses were variable: absent or low, normal, delayed, or persistently exaggerated. In conclusion, the CRH-stimulated F response pattern in hypopituitary patients was comparable to the urinary 17-OHCS and serum DOC response to metyrapone administration. Thus, F response pattern to CRH was useful in the evaluation of ACTH reserve in hypopituitary patients. ACTH response to CRH in ACTH-deficient patients was not consistently useful for ACTH reserve evaluation because of the variable response possibly resulting from a different etiology (hypothalamus versus pituitary) of ACTH deficiency. C1 UNIV ILLINOIS,COLL MED,DEPT PEDIAT,CHICAGO,IL 60612. NIH,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. FU NICHD NIH HHS [R01 HD 24360] NR 28 TC 8 Z9 8 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 AUG PY 1994 VL 36 IS 2 BP 215 EP 220 DI 10.1203/00006450-199408000-00013 PG 6 WC Pediatrics SC Pediatrics GA NY785 UT WOS:A1994NY78500013 PM 7970937 ER PT J AU HARRISON, J SHI, XL WANG, LY MA, JKH ROJANASAKUL, Y AF HARRISON, J SHI, XL WANG, LY MA, JKH ROJANASAKUL, Y TI NOVEL DELIVERY OF ANTIOXIDANT ENZYME CATALASE TO ALVEOLAR MACROPHAGES BY FC RECEPTOR-MEDIATED ENDOCYTOSIS SO PHARMACEUTICAL RESEARCH LA English DT Article DE MACROPHAGES; IMMUNE COMPLEX; CATALASE; OXIDATION; ENDOCYTOSIS ID PULMONARY OXYGEN-TOXICITY; SUPEROXIDE-DISMUTASE; INJURY; LUNG; CELLS AB Excessive production of reactive oxygen species by alveolar macrophages (AMs) in response to inhaled toxic substances is a major cause of oxidative lung injury. Therapeutic approaches designed to protect the lungs from oxidative injury by administering native antioxidant enzymes such as catalase and superoxide dismutase have been suggested. However, problems associated with poor penetration of these enzymes to the intracellular target sites have limited their effective use. The present study reports a drug targeting method based on receptor-mediated endocytosis of the antioxidant enzyme catalase to the AMs. This method employs molecular conjugate consisting of a cognate moiety, in this case IgG which recognizes the macrophage Fc receptor, covalently linked to the enzyme catalase via the reversible disulfide linkage. The uptake efficiency of the enzyme conjugate and its protection against oxidative injury were evaluated microfluorometrically using the intracellular oxidative probe dichlorodihydrofluorescein BSA: anti BSA antibody complex (DCHF-IC), and the cell viability indicator propidium iodide. The DCHF-IC-stimulated macrophages exhibited a dose- and time-dependent increase in intracellular fluorescence with a half maximal response dose of approximately 120 mu g/ml. Free catalase (50-500 U/ml) failed to inhibit the DCHF-IC-induced oxidative burst and had only a marginal protective effect on AM injury. In contrast, the catalase-IgG conjugate (50-500 U/ml) strongly inhibited both the DCHF-IC-induced oxidation and injury in a dose-dependent manner. Effective inhibition was shown to require both the antioxidant catalase moiety and the cognate moiety for the cell surface receptor. Specific internalization of the conjugate through the Fc receptor was also investigated by competitive inhibition using free IgG. Under this condition, the conjugate showed a much reduced protective effect on intracellular oxidation, indicating conjugate internalization through the Fc endocytosis pathway. Thus, the enzyme-IgG conjugate system may be used as an effective and selective means to deliver antioxidant enzymes to the intracellular oxidative targets of the AMs. C1 W VIRGINIA UNIV,HLTH SCI CTR,SCH PHARM,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506. NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. RI Shi, Xianglin/B-8588-2012; OI Rojanasakul, Yon/0000-0002-8839-6462 NR 19 TC 9 Z9 9 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD AUG PY 1994 VL 11 IS 8 BP 1110 EP 1114 DI 10.1023/A:1018976529766 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NZ366 UT WOS:A1994NZ36600008 PM 7971710 ER PT J AU STEPHENS, EA TAYLOR, JA KAPLAN, N YANG, CH HSIEH, LL LUCIER, GW BELL, DA AF STEPHENS, EA TAYLOR, JA KAPLAN, N YANG, CH HSIEH, LL LUCIER, GW BELL, DA TI ETHNIC VARIATION IN THE CYP2E1 GENE - POLYMORPHISM ANALYSIS OF 695 AFRICAN-AMERICANS, EUROPEAN-AMERICANS AND TAIWANESE SO PHARMACOGENETICS LA English DT Article ID N-ACETYLTRANSFERASE; LUNG-CANCER; SUSCEPTIBILITY; METABOLISM; EVOLUTION; P450IIE1; COMMON AB Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is involved in metabolism of many known carcinogens including N-nitrosodimethylamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variability in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environmental. Recently, two restriction fragment length polymorphisms (RFLPs) within the CYP2E1 gene have been suggested as genetic markers of risk for cancer. The first was a Rsa I polymorphism in the 5' regulatory region that appeared to alter transcriptional activation of the gene and the second was a Dra I polymorphism located similar to 7000 bp downstream in an intron. Rare alleles at each of these loci have been associated with a reduced risk for lung cancer in Japanese and Swedish populations. We have used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotype frequency for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, African-American or European-American background. Genotype and allele frequencies for Taiwanese were significantly different from those of African-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Americans were significantly different at the Rsa I site (P = 0.03). The rare alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiwanese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in European-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have been caused by a recombination event between these markers. If cancer susceptibility is modulated by the CYP2E1 DNA sequence variants we have described, then the presence of ethnic allele frequency differences suggests the possibility of differential susceptibility to environmentally caused cancer. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. CHANG GUNG MED COLL,DEPT PUBL HLTH,KAOHSIUNG,TAIWAN. OI taylor, jack/0000-0001-5303-6398 NR 19 TC 154 Z9 164 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1994 VL 4 IS 4 BP 185 EP 192 DI 10.1097/00008571-199408000-00002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA PE180 UT WOS:A1994PE18000002 PM 7987402 ER PT J AU LIPSKA, BK JASKIW, GE WEINBERGER, DR AF LIPSKA, BK JASKIW, GE WEINBERGER, DR TI THE EFFECTS OF COMBINED PREFRONTAL CORTICAL AND HIPPOCAMPAL DAMAGE ON DOPAMINE-RELATED BEHAVIORS IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE PREFRONTAL CORTEX; HIPPOCAMPUS; EXPLORATION; D-AMPHETAMINE; STEREOTYPY; APOMORPHINE; DOPAMINE ID IBOTENIC ACID LESIONS; NUCLEUS-ACCUMBENS-SEPTI; LOCOMOTOR-ACTIVITY; FRONTAL-CORTEX; MESOLIMBIC DOPAMINE; AMPHETAMINE; NEURONS; APOMORPHINE; TERMINALS; STRIATUM AB The effects of excitotoxic damage to both the medial prefrontal cortex (MPFC) and the ventral hippocampus (VH) on behaviors related to mesolimbic/nigrostriatal dopamine (DA) transmission were investigated in the rat. Locomotor activity in a novel environment, after injection of saline, and after d-amphetamine was assessed 2 and 4 weeks after ibotenic acid lesion of both MPFC and VH in adult rats. In addition, stereotypic behaviors and locomotion after apomorphine were evaluated 8 weeks after the lesion. Locomotor activity was significantly enhanced in all testing conditions in lesioned rats as compared with sham-operated animals, while oral stereotypic behaviors elicited by apomorphine were attenuated possibly because they were eclipsed by excessive locomotion. These data indicate that coexisting lesions of the MPFC and VH in adult rats produce potent and long-lasting effects on behaviors believed to be dependent primarily on the mesolimbic DA system. The profile of changes resembles more closely that observed after excitotoxic lesions of the VH alone rather than that after separate MPFC lesion. C1 VET ADM MED CTR,DEPT PSYCHIAT 116A,BRECKSVILLE,OH 44702. RP LIPSKA, BK (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 39 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 1994 VL 48 IS 4 BP 1053 EP 1057 DI 10.1016/0091-3057(94)90220-8 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PA431 UT WOS:A1994PA43100031 PM 7972285 ER PT J AU KOBAYASHI, T URABE, K WINDER, A TSUKAMOTO, K BREWINGTON, T IMOKAWA, G POTTERF, B HEARING, VJ AF KOBAYASHI, T URABE, K WINDER, A TSUKAMOTO, K BREWINGTON, T IMOKAWA, G POTTERF, B HEARING, VJ TI DHICA OXIDASE ACTIVITY OF TRP1 AND INTERACTIONS WITH OTHER MELANOGENIC ENZYMES SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT XVth International Pigment Cell Conference CY SEP 26-30, 1993 CL LONDON, ENGLAND SP INT FEDERAT PIGMENT CELL RES DE TYROSINASE; TRP1; PIGMENTATION; MELANOGENESIS ID TYROSINASE-RELATED PROTEIN; DOPACHROME TAUTOMERASE; MOUSE TYROSINASE; LOCUS; MELANOCYTES; FIBROBLASTS; EXPRESSION; CDNA; PIGMENTATION; MELANOMA AB Tyrosinase-related protein 1 (TRP1) maps to the brown locus in mice. Although the specific function of TRP1 has been in dispute, mutations in its structural gene result in the formation of brown rather than black melanin. We have investigated the melanogenic function of TRP1 by using immune-affinity purification of the protein and also by using transfection of its gene into fibroblasts to study its characteristics. We show that TRP1 has the ability to oxidize DHICA, a melanogenic intermediate derived from DOPAchrome. In addition, TRP1 has the ability to interact with tyrosinase and significantly stabilize the latter's catalytic function. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV OXFORD,SIR WILLIAM DUNN SCH PATHOL,OXFORD OX1 3RE,ENGLAND. KAO INST FUNDAMENTAL RES,TOCHIGI 32134,JAPAN. NR 25 TC 48 Z9 49 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD AUG PY 1994 VL 7 IS 4 BP 227 EP 234 DI 10.1111/j.1600-0749.1994.tb00054.x PG 8 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA PL618 UT WOS:A1994PL61800006 PM 7855068 ER PT J AU ELLIS, GB AF ELLIS, GB TI OFFICE FOR PROTECTION FROM RESEARCH RISKS (OPRR) SO POLITICS AND THE LIFE SCIENCES LA English DT Article RP ELLIS, GB (reprint author), NIH,OFF PROTECT RES RISKS,BLDG 31,ROOM 5B33,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BEECH TREE PUBLISHING PI GUILDFORD PA 10 WATFORD CLOSE, GUILDFORD, SURREY, ENGLAND GU1 2EP SN 0730-9384 J9 POLIT LIFE SCI JI Polit. Life Sci. PD AUG PY 1994 VL 13 IS 2 BP 271 EP 273 PG 3 WC Biology; History & Philosophy Of Science; Social Issues SC Life Sciences & Biomedicine - Other Topics; History & Philosophy of Science; Social Issues GA PV108 UT WOS:A1994PV10800024 PM 11654650 ER PT J AU CHEMERIS, VV DOLGIKH, DA FEDOROV, AN FINKELSTEIN, AV KIRPICHNIKOV, MP UVERSKY, VN PTITSYN, OB AF CHEMERIS, VV DOLGIKH, DA FEDOROV, AN FINKELSTEIN, AV KIRPICHNIKOV, MP UVERSKY, VN PTITSYN, OB TI A NEW APPROACH TO ARTIFICIAL AND MODIFIED PROTEINS - THEORY-BASED DESIGN, SYNTHESIS IN A CELL-FREE SYSTEM AND FAST TESTING OF STRUCTURAL-PROPERTIES BY RADIOLABELS SO PROTEIN ENGINEERING LA English DT Article DE BIOSYNTHESIS IN VITRO; DE NOVO PROTEINS; PROTEIN DESIGN; THEORY OF PROTEIN STRUCTURES ID MOLECULE SELF-ORGANIZATION; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; MESSENGER-RNA; DENOVO DESIGN; TRANSLATION SYSTEM; GLOBULAR-PROTEINS; BINDING DOMAIN; MOLTEN GLOBULE; ALPHA-HELICES AB A novel approach to the creation of artificial and modified proteins has been elaborated. The approach includes a sequence design based on the molecular theory of protein secondary structure and folding patterns, gene expression in a cell-free system and testing of structural properties of the synthesized polypeptides at a nanogram level using radiolabelled chains. The approach has been applied to a new synthetic protein albebetin which has been designed to form a 3-D fold which does not contradict any structural rule but has been never observed up to now in natural proteins, Using size-exclusion chromatography, urea-gradient electrophoresis and limited proteolysis of a radiolabelled chain, it has been shown that the artificial protein is nearly as compact as natural proteins, cooperatively unfolds at high urea concentrations and has some structural features of a definite structure consistent with the designed one. As albebetin has been designed as consisting of two structural repeats, a 'half-albebetin' (one of these repeats) has also been synthesized and studied. It was shown that 'half-albebetin' is also compact. C1 RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RUSSIAN ACAD SCI,INST MOLEC BIOL,MOSCOW 117984,RUSSIA. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Uversky, Vladimir/F-4515-2011; Dolgikh, Dmitry/F-2369-2014; Finkelstein, Alexey/M-1440-2015; OI Uversky, Vladimir/0000-0002-4037-5857; Finkelstein, Alexey/0000-0002-2138-4803; Dolgikh, Dmitry/0000-0002-9880-7202 NR 60 TC 18 Z9 18 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD AUG PY 1994 VL 7 IS 8 BP 1041 EP 1052 DI 10.1093/protein/7.8.1041 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PC685 UT WOS:A1994PC68500014 PM 7809031 ER PT J AU BORK, P KOONIN, EV AF BORK, P KOONIN, EV TI A NEW FAMILY OF CARBON-NITROGEN HYDROLASES SO PROTEIN SCIENCE LA English DT Note DE ENZYME EVOLUTION; HOMOLOGY SEARCH; NITROGEN METABOLISM ID CYANIDE HYDRATASE; CLONING; GENE; ALIGNMENT; NITRILASE; IDENTIFICATION; PURIFICATION; EXPRESSION; SEQUENCES; SEARCH AB Using computer methods for database search and multiple alignment, statistically significant sequence similarities were identified between several nitrilases with distinct substrate specificity, cyanide hydratases, aliphatic amidases, beta-alanine synthase, and a few other proteins with unknown molecular function. All these proteins appear to be involved in the reduction of organic nitrogen compounds and ammonia production. Sequence conservation over the entire length, as well as the similarity in the reactions catalyzed by the known enzymes in this family, points to a common catalytic mechanism. The new family of enzymes is characterized by several conserved motifs, one of which contains an invariant cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes an invariant glutamic acid that might also be involved in catalysis. C1 MAX DELBRUCK CTR MOLEC MED,D-13125 BERLIN,GERMANY. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP BORK, P (reprint author), EUROPEAN MOLEC BIOL LAB,MEYERHOFSTR 1,D-69117 HEIDELBERG,GERMANY. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 18 TC 77 Z9 80 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1994 VL 3 IS 8 BP 1344 EP 1346 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE332 UT WOS:A1994PE33200021 PM 7987228 ER PT J AU GRONENBORN, AM CLORE, GM AF GRONENBORN, AM CLORE, GM TI WHERE IS NMR TAKING US SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Editorial Material ID NUCLEAR-MAGNETIC-RESONANCE; DISTANCE GEOMETRY; PROTEIN-STRUCTURE; X-RAY; SPECTROSCOPY; SPECTRA; REFINEMENT; CRYSTAL RP GRONENBORN, AM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 27 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD AUG PY 1994 VL 19 IS 4 BP 273 EP 276 DI 10.1002/prot.340190402 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PB473 UT WOS:A1994PB47300001 PM 7984623 ER PT J AU DUBERSTEIN, PR CONWELL, Y CAINE, ED AF DUBERSTEIN, PR CONWELL, Y CAINE, ED TI AGE-DIFFERENCES IN THE PERSONALITY-CHARACTERISTICS OF SUICIDE COMPLETERS - PRELIMINARY FINDINGS FROM A PSYCHOLOGICAL AUTOPSY STUDY SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID 5-FACTOR MODEL; PSYCHIATRIC-PATIENTS; ADOLESCENT SUICIDE; SPOUSE RATINGS; SELF-REPORTS; DISORDERS; LIFE; ALCOHOLISM RP DUBERSTEIN, PR (reprint author), UNIV ROCHESTER,MED CTR,DEPT PSYCHIAT,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,ROCHESTER,NY 14642, USA. NR 57 TC 83 Z9 84 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD AUG PY 1994 VL 57 IS 3 BP 213 EP 224 PG 12 WC Psychiatry SC Psychiatry GA PH219 UT WOS:A1994PH21900002 PM 7800770 ER PT J AU LIU, HC CHOU, P LIN, KN WANG, SJ FUH, JL LIN, HC LIU, CY WU, GS LARSON, EB WHITE, LR GRAVES, AB TENG, EL AF LIU, HC CHOU, P LIN, KN WANG, SJ FUH, JL LIN, HC LIU, CY WU, GS LARSON, EB WHITE, LR GRAVES, AB TENG, EL TI ASSESSING COGNITIVE-ABILITIES AND DEMENTIA IN A PREDOMINANTLY ILLITERATE POPULATION OF OLDER INDIVIDUALS IN KINMEN SO PSYCHOLOGICAL MEDICINE LA English DT Article ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; EDUCATION; PREVALENCE; SHANGHAI; SCALE AB A community survey of dementia was conducted on a Chinese islet. A total of 221 men and 234 women in the age range of 50-92 were assessed. The Cognitive Abilities Screening Instrument (CASI), a 100-point cognitive test designed for cross-cultural studies and adapted in Chinese for individuals with little or no formal education, was administered twice by trained field workers with a retest interval of 3 to 4 weeks. In addition, all participants were assessed by physicians who did not know the CASI scores. The physicians' assessment included a complete neurological examination, plus semi-structured tests and interviews covering cognitive abilities, daily activities, depression, cerebrovascular disease, and Parkinson's disease. Dementia was diagnosed by consensus among the physicians according to the DSM-III-R criteria. Among the 455 participants, 16 cases of dementia were identified, including 13 with probable Alzheimer's disease and 1 each with vascular dementia, Parkinson's disease, and alcoholism. The rates of dementia were 0, 3.9 and 11.5% for the age groups of 50-69, 70-79 and 80-92; and 4.4, 2.0 and 0% for the education groups of 0-1, 2-6 and 7-15 years of schooling. No sex difference was found after controlling for education. The Chinese version of the CASI had an intraclass retest reliability of 0.90. Using a cut-off score of less than or equal to 50 for dementia, the sensitivity was 0.88 and the specificity was 0.94. The preliminary study suggests that the CASI can be used in Chinese populations with generally low education levels and that Alzheimer's disease was the most common type of dementia in this population. C1 NATL YANG MING MED COLL,INST PUBL HLTH,TAIPEI 11221,TAIWAN. CHANG GUNG MEM HOSP,DEPT PSYCHIAT,TAIPEI 10591,TAIWAN. BUR PUBL HLTH & ENVIRONM PROTECT,KINMEN,PEOPLES R CHINA. UNIV WASHINGTON,DEPT MED EPIDEMIOL & HLTH SERV,SEATTLE,WA. BATTELLE SEATTLE RES CTR,SEATTLE,WA. NIA,HONOLULU ASIA AGING STUDY,HONOLULU,HI. UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90033. RP LIU, HC (reprint author), VET GEN HOSP,INST NEUROL,TAIPEI,TAIWAN. OI Fuh, Jong-Ling/0000-0001-9135-3351 NR 24 TC 88 Z9 92 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 1994 VL 24 IS 3 BP 763 EP 770 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA PE052 UT WOS:A1994PE05200023 PM 7991758 ER PT J AU LUIJCKX, NBL RAO, GN MCCONNELL, EE WURTZEN, G KROES, R AF LUIJCKX, NBL RAO, GN MCCONNELL, EE WURTZEN, G KROES, R TI THE INTAKE OF CHEMICALS RELATED TO AGE IN LONG-TERM TOXICITY STUDIES - CONSIDERATIONS FOR RISK ASSESSMENT SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID BODY-WEIGHT; F344 RATS; CARCINOGENICITY; SURVIVAL AB The estimation of acceptable daily intake (ADI) is generally based on results from long-term toxicity studies. Long-term exposure of rodent and nonrodent species is extrapolated to lifetime exposure in humans, using uncertainty factors to compensate inter- and intraspecies differences. Special consideration can be given to groups of humans at increased risk, such as children, due to higher susceptibility or higher predicted intake. A retrospective study of long-term carcinogenesis studies was performed at the National Toxicology Program of the National Institute of Environmental Health Sciences to gain insight into the relationship between age and intake of test compounds. In these long-term studies, average intake of feed and drinking water, and consequently chemicals dosed in these, was approximately two times higher on a body weight basis in young animals (postweaning) than in adults. Thus, estimating an ADI from the NOEL of this type of studies already includes a higher dose for the young. When maximum levels for food additives are being set using the already established ADI, it may not be necessary to add an additional uncertainty factor for different ages, unless there are other specific reasons to do so, such as unduly high exposure and toxicity at a certain age. Compared to intake per kilogram of body weight at the end of the study, the ADI already includes an extra uncertainty factor of approximately 2 for young individuals. (C) 1994 Academic Press, Inc. C1 NIEHS,RES TRIANGLE PK,NC. COCA COLA NORDIC,OSLO,NORWAY. NO EURASIA DIV,OSLO,NORWAY. RP LUIJCKX, NBL (reprint author), NATL INST PUBL HLTH & ENVIRONM PROTECT,CTR TOXICOL ADVISORY,POB 1,3720 BA BILTHOVEN,NETHERLANDS. NR 27 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1994 VL 20 IS 1 BP 96 EP 104 DI 10.1006/rtph.1994.1038 PN 1 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA PK381 UT WOS:A1994PK38100006 PM 7838994 ER PT J AU WAALKES, MP INFANTE, P HUFF, J AF WAALKES, MP INFANTE, P HUFF, J TI THE SCIENTIFIC FALLACY OF ROUTE SPECIFICITY OF CARCINOGENESIS WITH PARTICULAR REFERENCE TO CADMIUM SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Note ID CHEMICALS; RATS C1 US OCCUPAT SAFETY & HLTH ADM,HLTH STAND PROGRAM,WASHINGTON,DC 20210. NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 17 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1994 VL 20 IS 1 BP 119 EP 121 DI 10.1016/S0273-2300(05)80009-1 PN 1 PG 3 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA PK381 UT WOS:A1994PK38100008 PM 7838989 ER PT J AU LUNDGREN, JD RIEVES, RD MULLOL, J LOGUN, C SHELHAMER, JH AF LUNDGREN, JD RIEVES, RD MULLOL, J LOGUN, C SHELHAMER, JH TI THE EFFECT OF NEUTROPHIL PROTEINASE ENZYMES ON THE RELEASE OF MUCUS FROM FELINE AND HUMAN AIRWAY CULTURES SO RESPIRATORY MEDICINE LA English DT Article ID RESPIRATORY GLYCOCONJUGATE RELEASE; PLATELET-ACTIVATING-FACTOR; TRACHEAL EPITHELIAL-CELLS; CIGARETTE SMOKERS; ORGAN-CULTURE; MUCIN RELEASE; ELASTASE; SURFACE; PROTEINASES; SECRETION C1 NIAID,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP LUNDGREN, JD (reprint author), UNIV COPENHAGEN,HVIDOVRE HOSP,DEPT INFECT DIS 144,DK-2650 HVIDOVRE,DENMARK. OI Lundgren, Jens/0000-0001-8901-7850 NR 33 TC 32 Z9 33 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0954-6111 J9 RESP MED JI Respir. Med. PD AUG PY 1994 VL 88 IS 7 BP 511 EP 518 DI 10.1016/S0954-6111(05)80333-6 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA PE039 UT WOS:A1994PE03900007 PM 7972975 ER PT J AU POHIDA, TJ FREDRICKSON, HA TSCHUDIN, RG FESSLER, JF KRISHNA, MC BOURG, J HARRINGTON, F SUBRAMANIAN, S AF POHIDA, TJ FREDRICKSON, HA TSCHUDIN, RG FESSLER, JF KRISHNA, MC BOURG, J HARRINGTON, F SUBRAMANIAN, S TI HIGH-SPEED DIGITIZER/AVERAGER DATA-ACQUISITION SYSTEM FOR FOURIER-TRANSFORM ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID SPECTROMETER; FREQUENCY AB A high-speed digitizer/averager data-acquisition system designed and built as part of a 300-MHz Fourier transform electron paramagnetic resonance spectrometer is described. There are two key features of the system: (1) the maximum digitizing rate is 300 Msamples/s and (2) a 256-point free-induction-decay signal running summation can be updated in less than 3 mu s. At the maximum digitizing rate, the system can sum 65 536 FIDs in 220 ms. The system consists of an analog-to-digitar converter/adder unit (ADCA) and an IBM compatible personal computer. The ADCA is comprised of a digitizer, high-speed sample buffers, high-speed adders/memory, and control hardware. Design techniques, such as parallel processing, utilized to meet the high-speed performance requirements are described. Trigger and timing signals for the system are derived from the spectrometer. System efficiency, synchronization, and time base stability are demonstrated in the spectrometer at a sampling frequency of 200 MHz. Signal-to-noise ratio enhancements are shown using a lithium phthalocyanine test sample. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,ELECT & ELECTR ENGN SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,PERSONAL COMP BRANCH,BETHESDA,MD 20892. NIDDKD,CHEM PHYS LAB,NMR SECT,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,RES INSTRUMENTAT SECT,BETHESDA,MD 20892. RP POHIDA, TJ (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT BIOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 18 Z9 18 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD AUG PY 1994 VL 65 IS 8 BP 2500 EP 2504 DI 10.1063/1.1145223 PG 5 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA PC319 UT WOS:A1994PC31900009 ER PT J AU MAGNUSON, NS BECK, T VAHIDI, H HAHN, H SMOLA, U RAPP, UR AF MAGNUSON, NS BECK, T VAHIDI, H HAHN, H SMOLA, U RAPP, UR TI THE RAF-1 SERINE/THREONINE PROTEIN-KINASE SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE SIGNAL TRANSDUCTION; MEK; RAS; MITOGENESIS; DIFFERENTIATION ID COMPLETE CODING SEQUENCE; MITOGENIC SIGNAL-TRANSDUCTION; SERINE THREONINE KINASE; MAP KINASE; BIOLOGICAL-ACTIVITY; V-RAF; A-RAF; ACTIVATION; PHOSPHORYLATION; GROWTH AB Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and survival. Regulation of Raf-1 activity is complex and involves Ras, as well as several serine/threonine and tyrosine kinases. Through a series of phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class transcription factors via phosphorylation of specific serine residues. Under ordinary circumstances, the cascade involving Raf-1 eventually leads to changes in gene expression and protein synthesis. Upon constitutive activation of Raf-1 kinase, as a result of genetic changes, a variety of cell types acquire a transformed phenotype. C1 NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, BCDP, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES FACIL, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21701 USA. UNIV WURZBURG, INST MED RADIOBIOL & CELL BIOL, D-97078 WURZBURG, GERMANY. RP WASHINGTON STATE UNIV, DEPT MICROBIOL, PULLMAN, WA 99164 USA. NR 64 TC 62 Z9 63 U1 1 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 1994 VL 5 IS 4 BP 247 EP 253 PG 7 WC Oncology SC Oncology GA PD306 UT WOS:A1994PD30600003 PM 7803760 ER PT J AU BLOT, WJ AF BLOT, WJ TI ESOPHAGEAL CANCER TRENDS AND RISK-FACTORS SO SEMINARS IN ONCOLOGY LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; GASTRIC CARDIA; UNITED-STATES; BLACK-MEN; ADENOCARCINOMA; ALCOHOL; CHINA; TOBACCO; LINXIAN RP BLOT, WJ (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN SUITE 431,BETHESDA,MD 20892, USA. NR 53 TC 173 Z9 182 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1994 VL 21 IS 4 BP 403 EP 410 PG 8 WC Oncology SC Oncology GA PB652 UT WOS:A1994PB65200002 PM 8042037 ER PT J AU MCCARREN, M GOLDBERG, J RAMAKRISHNAN, V FABSITZ, R AF MCCARREN, M GOLDBERG, J RAMAKRISHNAN, V FABSITZ, R TI INSOMNIA IN VIETNAM ERA VETERAN TWINS - INFLUENCE OF GENES AND COMBAT EXPERIENCE SO SLEEP LA English DT Article DE GENETICS; SLEEP; TWINS; COMBAT; INSOMNIA ID POSTTRAUMATIC-STRESS-DISORDER; SLEEP DISTURBANCE; REGISTRY; PREVALENCE; WAR AB Genetic and environmental influences on insomnia were studied in 2,825 pairs of Vietnam era veteran male twins. The self-reported sleep problems studied included trouble falling asleep, trouble staying asleep, waking often, waking tired and a composite sleep scale. Twin correlations for each of the sleep problems were larger in monozygotic than in dizygotic pairs, with heritability estimates ranging from 0.21 to 0.42. There was no effect of common familial environment. Phenotypic correlations for combat experience and sleep problems were small, ranging from 0.00 to 0.09, with no differences seen in monozygotic and dizygotic twins. When the effects of genes and combat exposure were evaluated simultaneously, there was a significant genetic contribution to all sleep measures, but combat exposure was significantly associated only with overall sleep quality, waking often and having trouble staying asleep. C1 EDWARD HINES JR VET ADM HOSP,VIETNAM ERA TWIN REGISTRY,HINES,IL 60141. UNIV ILLINOIS,SCH PUBL HLTH,EPIDEMIOL BIOSTAT PROGRAM,CHICAGO,IL. EDWARD HINES JR VET ADM HOSP,VA COOPERAT STUDIES PROGRAM COORDINATING CTR,HINES,IL 60141. NHLBI,BETHESDA,MD 20892. FU NIA NIH HHS [R01-AG10430]; NIDA NIH HHS [R01-DA04604] NR 27 TC 50 Z9 51 U1 3 U2 5 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD AUG PY 1994 VL 17 IS 5 BP 456 EP 461 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PE286 UT WOS:A1994PE28600010 PM 7991958 ER PT J AU ORY, MG COX, DM AF ORY, MG COX, DM TI FORGING AHEAD - LINKING HEALTH AND BEHAVIOR TO IMPROVE QUALITY-OF-LIFE IN OLDER-PEOPLE SO SOCIAL INDICATORS RESEARCH LA English DT Article; Proceedings Paper CT Colloquium on Improving the Quality of Life in Normal and Disabled Populations CY 1991 CL UNIV CALGARY, CALGARY, CANADA HO UNIV CALGARY ID URINARY-INCONTINENCE; CLINICAL-TRIAL; WOMEN; CANCER; CARE AB This chapter will focus on conceptual and methodological issues related to health promotion/disability prevention for older people. The first section will begin with a discussion of why older people, as compared to younger persons, are not traditionally seen as targets of health promotion efforts. In recent years several national working groups have been established to examine how older people's health and functioning can be improved. Their objectives and recommendations for older Americans will be reviewed. The second section will address the conceptual framework underlying health and behavior research supported by the National Institute on Aging. Tle movement from correlational studies to studies of basic mechanisms linking health and behaviour will be discussed, with particular attention to interactions with aging processes. Examples of health and behavior research representing these processes will be presented as well as methodological issues in the measurement of health and functional outcomes for older people. Measurement of quality of life in the cognitively impaired is seen as especially difficult. The third section will review several common themes emanating from these research studies. These include attention to a life course perspective, variability in aging processes, alternative research approaches, and intervention strategies for both initiating and maintaining recommended behavioral changes. A fourth section will review current areas of investigation at the National Institute of Aging. Successful intervention strategies in both community and institutional settings will to presented. These include: (1) a comprehensive behavioral and environmental falls prevention program which has been shown to reduce falls in the community; (2) a health education program to increase older women's use of cancer-related health practices; and (3) behavioral strategies for reducing incontinence in nursing homes. A new NIA initiative on special care units for persons with dementia will also be discussed. The fifth and final section will deal with issues involved in the translation of research into policy and practice. Approaches for increasing the relevance of research to policymakers will be discussed. RP ORY, MG (reprint author), NIA,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892, USA. NR 61 TC 19 Z9 19 U1 3 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0303-8300 J9 SOC INDIC RES JI Soc. Indic. Res. PD AUG PY 1994 VL 33 IS 1-3 BP 89 EP 120 DI 10.1007/BF01078959 PG 32 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA PD033 UT WOS:A1994PD03300004 ER PT J AU YEO, JH DEMURA, M ASAKURA, T FUJITO, T IMANARI, M NICHOLSON, LK CROSS, TA AF YEO, JH DEMURA, M ASAKURA, T FUJITO, T IMANARI, M NICHOLSON, LK CROSS, TA TI STRUCTURAL-ANALYSIS OF HIGHLY ORIENTED POLY(P-PHENYLENE TEREPHTHALAMIDE) BY N-15 SOLID-STATE NUCLEAR-MAGNETIC-RESONANCE SO SOLID STATE NUCLEAR MAGNETIC RESONANCE LA English DT Article DE N-15 NUCLEAR MAGNETIC RESONANCE; ORIENTATIONAL CONSTRAINTS; POLY(P-PHENYLENE TEREPHTHALAMIDE); POLYMER STRUCTURE; ORIENTED SAMPLES ID CHEMICAL-SHIFT; NMR; POLYPEPTIDE; GRAMICIDIN; FIBERS; CONFORMATION; POLYMERS AB The structure of an aromatic polyamide, poly(p-phenylene-terephthalamide) (PPTA), was studied in the solid state using N-15 nuclear magnetic resonance (NMR) spectroscopy. Spectra of uniaxially aligned molecules placed with the axis of alignment both parallel with and perpendicular to the applied magnetic field were analyzed to yield the orientations of specific molecular bonds with. respect to the fiber axis. The N-15 chemical shift tensor was characterized by simulating powder pattern spectra of both PPTA and a model compound, benzanilide. Chemical shift and dipolar coupled chemical shift line shapes were calculated through Euler angle transformations from the principal axis system (PAS) reference frame to the fiber axis system (FAS) frame. The orientations of NH and NC' bonds in PPTA are determined as well as the orientational distribution of the PPTA fiber axis. The structural parameters determined for PPTA are compared with those obtained by X-ray diffraction. C1 FLORIDA STATE UNIV,NATL HIGH MAGNET FIELD LAB,1800 E PAUL DIRAC DR,TALLAHASSEE,FL 32306. NIDR,BETHESDA,MD 20892. JEOL LTD,TOKYO 196,JAPAN. TOKYO UNIV AGR & TECHNOL,FAC TECHNOL,DEPT BIOTECHNOL,KOGANEI,TOKYO 184,JAPAN. RI Demura, Makoto/F-5272-2011; Asakura, Tetsuo/B-9970-2013 NR 20 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-2040 J9 SOLID STATE NUCL MAG JI Solid State Nucl. Magn. Reson. PD AUG PY 1994 VL 3 IS 4 BP 209 EP 218 DI 10.1016/0926-2040(94)90041-8 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Physics, Condensed Matter; Spectroscopy SC Chemistry; Physics; Spectroscopy GA PB491 UT WOS:A1994PB49100003 PM 7834320 ER PT J AU CUNNINGHAM, DS CUTLER, GB AF CUNNINGHAM, DS CUTLER, GB TI SPONTANEOUS VULVAR NECROTIZING FASCIITIS CUSHINGS-SYNDROME SO SOUTHERN MEDICAL JOURNAL LA English DT Note AB Necrotizing fasciitis is a potentially fatal condition, and the prognosis is worsened by immunosuppression. We describe what appears to be the first reported case of spontaneous vulvar necrotizing fasciitis occurring in a woman with uncontrolled hypercortisolism due to an ACTH-secreting thymic carcinoid tumor. C1 NICHHD,DEV ENDOCRINE BRANCH,BETHESDA,MD. NR 7 TC 2 Z9 2 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD AUG PY 1994 VL 87 IS 8 BP 837 EP 838 DI 10.1097/00007611-199408000-00018 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PB488 UT WOS:A1994PB48800018 PM 8052898 ER PT J AU BOLD, RJ WARREN, RE ISHIZUKA, J CHOCHUNG, YS TOWNSEND, CM THOMPSON, JC AF BOLD, RJ WARREN, RE ISHIZUKA, J CHOCHUNG, YS TOWNSEND, CM THOMPSON, JC TI EXPERIMENTAL GENE-THERAPY OF HUMAN COLON-CANCER SO SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 1994 CL JACKSON, MS SP SOC UNIV SURGEONS ID SIGNAL TRANSDUCING PROTEINS; CYCLIC-AMP ANALOGS; CELL-GROWTH; 8-CHLORO-CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; REGULATORY SUBUNIT; ANTISENSE; SUPPRESSION; EXPRESSION; KINASE; DIFFERENTIATION AB Background. Gastrin regulates growth of human colon cancer cells by activation of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA). Gastrin and 8-Br-cAMP, a membrane-permeable cAMP analog, inhibit growth of HCT116 cells; both stimulate growth of LoVo cells. This dual effect on growth may be explained by relative amounts of the regulatory subunit (R(I alpha) or R(II beta)) of PKA within the cancer cells. Antisense oligodeoxynucleotides (ASO) to either R(I alpha) or R(II beta) inhibit protein translation of the target mRNA by sequence-specific binding; subsequently, cellular PKA content and the cAMP-mediated growth may be altered. We determined whether ASO to either the R(I alpha) or R(II beta) subunit altered the cAMP-mediated growth of HCT116 and LoVo human colon cancer cells. Methods. HCT116 cells were treated with R(II beta) ASO (15 mu mol/L, 4 days) and then treated with 8-Br-cAMP (25 mu mol/L); tritiated thymidine incorporation was measured after 24 hours, and the cell number was determined on alternate days. Protein and mRNA levels of the R(II beta) subunit were determined by Western and Northern blotting, respectively. Similar studies with an ASO against the R(I alpha) subunit were performed on LoVo cells. Results R(II beta) ASO reversed the cAMP-mediated inhibition of growth of HCT116 cells, and R(II beta) ASO decreased the protein level of the R(II beta) subunit. R(II beta) ASO did not alter the basal growth of HCT116 cells. R(I alpha) ASO reversed the cAMP-mediated stimulation of the growth of LoVo cells. Conclusions. The regulatory subunits of PKA are potential targets to alter growth of human colon cancer cells. Gene therapy directed to alter specific steps in signal transduction pathways may provide new therapeutic strategies. C1 UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX 77555. UNIV CALIF DAVIS,OAKLAND,CA. NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892. FU NIDDK NIH HHS [P01 DK35608, 5R37 DK15241] NR 25 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1994 VL 116 IS 2 BP 189 EP 196 PG 8 WC Surgery SC Surgery GA PA544 UT WOS:A1994PA54400010 PM 8047985 ER PT J AU LANE, NJ BALBO, A STOLL, J RAPOPORT, SI AF LANE, NJ BALBO, A STOLL, J RAPOPORT, SI TI LONG-TERM INTRACEREBRAL TRANSPLANTS OF FETAL HIPPOCAMPUS FROM MOUSE TRISOMY-16, A MODEL FOR DOWNS-SYNDROME (TRISOMY-21), DO NOT EXHIBIT ALZHEIMERS-DISEASE NEUROPATHOLOGY BY ULTRASTRUCTURAL CRITERIA SO TISSUE & CELL LA English DT Article DE HIPPOCAMPUS; ANIMAL MODEL; DOWNS SYNDROME; ALZHEIMERS DISEASE; INTRACEREBRAL GRAFTS; MOUSE TRISOMY 16; NEUROPATHOLOGY; BRAIN TRANSPLANTS ID HUMAN CHROMOSOME-21; DEMENTIA; BRAIN; PATHOLOGY; PRESENILE; PROTEINS; NEURONS; REGION; GRAFTS; MICE AB Murine trisomy 16 (Ts16) is an animal model for Down's syndrome (human trisomy 21), because mouse chromosome 16 is genetically homologous to human chromosome 21. Down's syndrome patients, older than 35 years, demonstrate the neuropathological and neurochemical defects characteristic of Alzheimer's disease and Ts16 mouse fetuses exhibit phenotypic abnormalities similar to those in Down's syndrome fetuses. Trisomic mouse fetuses, however, die in utero, and so do not survive long enough for their brains to develop the degenerative changes of aging. This can be overcome by grafting the fetal Ts16 hippocampus (an early site for the development of the pathological features characteristic of Alzheimer's disease), into the cerebral ventricle or striatum of a normal adult mouse host. We have made such transplants, which have survived for up to 12 months. Examining these grafts ultrastructurally at various stages from 1 to 12 months, and comparing them with normal control grafts, reveals no structural difference that could be deemed characteristic of Alzheimer disease; no neurofibrillary tangle or senile plaque was observed. These observations, together with the normal structure of the neuronal organelles in trisomic hippocampal tissue, suggest that trisomic mouse grafts are not a useful model for Alzheimer's disease, despite earlier reports to the contrary. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. RP UNIV CAMBRIDGE, DEPT ZOOL, DOWNING ST, CAMBRIDGE CB2 3EJ, ENGLAND. NR 39 TC 7 Z9 7 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD AUG PY 1994 VL 26 IS 4 BP 477 EP 488 DI 10.1016/0040-8166(94)90001-9 PG 12 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA NY245 UT WOS:A1994NY24500001 PM 8091421 ER PT J AU KAVANAGH, JF LYON, GR AF KAVANAGH, JF LYON, GR TI ADD AND ITS RELATIONSHIP TO SPOKEN AND WRITTEN LANGUAGE - FOREWORD SO TOPICS IN LANGUAGE DISORDERS LA English DT Editorial Material RP KAVANAGH, JF (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD AUG PY 1994 VL 14 IS 4 BP R5 EP R7 PG 3 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA NW984 UT WOS:A1994NW98400002 ER PT J AU CHAN, PC MAHLER, J BUCHER, JR TRAVLOS, GS REID, JB AF CHAN, PC MAHLER, J BUCHER, JR TRAVLOS, GS REID, JB TI TOXICITY AND CARCINOGENICITY OF RIDDELLIINE FOLLOWING 13 WEEKS OF TREATMENT TO RATS AND MICE SO TOXICON LA English DT Article ID UNSCHEDULED DNA-SYNTHESIS; ORGAN WEIGHT DATA; PYRROLIZIDINE ALKALOIDS; MONOCROTALINE PYRROLE; PERIPHERAL-BLOOD; VAGINAL CYTOLOGY; CHEMICALS; INDUCTION; INVITRO; ASSAY AB Toxicity studies of riddelliine, a member of a class of pyrrolizidine alkaloids, were conducted because riddelliine has been found to contaminate human food sources. Groups of male and female Fischer rats were administered riddelliine by gavage in phosphate buffer at doses up to 10 mg/kg, and B6C3F1 mice at doses up to 25 mg/kg, five times a week. The animals were necropsied after 13 weeks of treatment or after a 7 or 14 week recovery period. Body weight gains were inversely related to dose in both rats and mice. Body weight of the 1.0 and 3.3 mg/kg female rats and 10.0 and 25.0 mg/kg mice remained depressed during the 14 week recovery period. At 13 weeks, significant findings included dose-related hepatopathy and intravascular macrophage accumulation in rats and hepatocytomegaly in mice. During the 14 week recovery period these lesions persisted and hepatic foci of cellular alteration in male rats and bile duct proliferation in female rats and male and female mice increased in severity. In the 10 mg/kg group of female rats adenomas of the liver occurred in two of ten at 13 weeks and in one of five at the 14 week recovery period. In separate studies, the frequency of micronucleated erythrocytes in peripheral blood was increased in male mice administered a single dose (150 mg/kg) of riddelliine. Increases in unscheduled DNA and S-phase syntheses were detected in primary hepatocytes from rats and mice treated with riddelliine at doses up to 25.0 mg/kg for 5 or 30 days. In mating trials in rats and mice, pup weights from treated dams at birth and during suckling were lower than controls. Thus, riddelliine is genotoxic and carcinogenic and may cross the placenta and/or be found in milk, causing developmental toxicity in rodents. C1 SRI INT,MENLO PK,CA 94025. RP CHAN, PC (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 36 Z9 36 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD AUG PY 1994 VL 32 IS 8 BP 891 EP 908 DI 10.1016/0041-0101(94)90368-9 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PA941 UT WOS:A1994PA94100005 PM 7985194 ER PT J AU VOGEL, FR AF VOGEL, FR TI UPDATE ON PRECLINICAL STUDIES OF HIV VACCINES SO TRANSFUSION LA English DT Meeting Abstract C1 NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,PRECLIN DEV SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1994 VL 34 IS 8 BP 730 EP 731 PG 2 WC Hematology SC Hematology GA PD361 UT WOS:A1994PD36100026 ER PT J AU KETTER, N FAST, P WALKER, MC WESCOTT, SL SCHULTZ, AM AF KETTER, N FAST, P WALKER, MC WESCOTT, SL SCHULTZ, AM TI PHASE-I AND PHASE-II TRIALS OF CANDIDATE-PREVENTIVE HIV VACCINES SO TRANSFUSION LA English DT Meeting Abstract C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1994 VL 34 IS 8 BP 731 EP 731 PG 1 WC Hematology SC Hematology GA PD361 UT WOS:A1994PD36100027 ER PT J AU BORODOVSKY, M KOONIN, EV RUDD, KE AF BORODOVSKY, M KOONIN, EV RUDD, KE TI NEW GENES IN OLD SEQUENCE - A STRATEGY FOR FINDING GENES IN THE BACTERIAL GENOME SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ESCHERICHIA-COLI GENOME; DATABASES; PROTEINS; REGIONS; SEARCH; CELL C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RP GEORGIA INST TECHNOL, SCH BIOL, ATLANTA, GA 30332 USA. FU NHGRI NIH HHS [HG00783]; NIGMS NIH HHS [GM47853] NR 27 TC 44 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1994 VL 19 IS 8 BP 309 EP 313 DI 10.1016/0968-0004(94)90067-1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC236 UT WOS:A1994PC23600001 PM 7940673 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - LONG AND ACCURATE PCR SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some problems encountered during the amplification of large DNA segments by the polymerase chain reaction (PCR), acid gives tips for doing long and accurate PCR. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1994 VL 19 IS 8 BP 341 EP 341 DI 10.1016/0968-0004(94)90074-4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC236 UT WOS:A1994PC23600008 PM 7940680 ER PT J AU BALLA, T CATT, KJ AF BALLA, T CATT, KJ TI PHOSPHOINOSITIDES AND CALCIUM SIGNALING - NEW ASPECTS AND DIVERSE FUNCTIONS IN CELL REGULATION SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ADRENAL GLOMERULOSA CELLS; INOSITOL TRISPHOSPHATE RECEPTOR; PHOSPHOLIPASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; RAT-LIVER; PROTEIN; TETRAKISPHOSPHATE; ACTIVATION; KINASE; 1,4,5-TRISPHOSPHATE AB Numerous circulating and locally produced hormones bind to specific cell-surface receptors and activate a variety of second-messenger pathways that evoke characteristic phenotypic responses in their target cells. One of the most ubiquitous signal transduction mechanisms is the phosphoinositide-calcium messenger system, which is activated by hormones, neurotransmitters, and growth factors. Stimulation of these receptors by their ligands causes a characteristic change in the metabolism of membrane phospholipids with production of diacylglycerol and a vapid increase in cytoplasmic Ca2+ concentration, due to the release of stored intracellular Ca2+ and stimulated Ca2+ entry from the extracellular space. These intracellular signals act in concert to activate protein kinases that phosphorylate a variety of regulatory proteins. The link between phosphoinositide turnover and Ca2+ mobilization is inositol 1,4,5-trisphosphate, the major Ca2+-mobilizing second messenger, which is produced from membrane phosphoinositides by activated phospholipase C enzymes. The mechanisms of ligand-regulated Ca2+ influx and the additional regulatory role(s) of phosphoinositides and inositol phosphates ave still being unfolded. This review and the following article summarize some recent developments and unsolved issues about this major signal transduction cascade that links calcium-mobilizing hormone receptors to the regulation of endocrine cell function. RP BALLA, T (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 63 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD AUG PY 1994 VL 5 IS 6 BP 250 EP 255 DI 10.1016/1043-2760(94)P3084-K PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PM598 UT WOS:A1994PM59800005 PM 18407216 ER PT J AU PUTNEY, JW BIRD, GS AF PUTNEY, JW BIRD, GS TI CALCIUM MOBILIZATION BY INOSITOL PHOSPHATES AND OTHER INTRACELLULAR MESSENGERS SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CYCLIC ADP-RIBOSE; 1,4,5-TRISPHOSPHATE-SENSITIVE ORGANELLE; PLASMA-MEMBRANE; CA-2+ RELEASE; ACINAR-CELLS; CA2+ ENTRY; RAT-LIVER; RECEPTOR; TRISPHOSPHATE; INFLUX AB Inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] is now widely recognized as a messenger controlling the release of calcium from intracellular stores. In oocytes, and also probably in. excitable cells, another potential calcium-mobilizing messenger is cyclic ADP ribose, although there is as yet little evidence that its levels are regulated by hormones or other extracellular mediators. In addition to signaling intracellular calcium release, [Ins(1,4,5)P-3] also regulates calcium entry across the plasma membrane, but not in a direct manner Rather the depletion of intracellular stores by the calcium-mobilizing action of [Ins(1,4,5)P-3] initiates a process of retrograde signaling whereby the depleted stoves generate or release a diffusible messenger that is believed to act on the plasma membrane. A phosphorylated metabolite of [Ins(1,4,5)P-3], inositol 1,3,4,5-tetrakisphosphate [Ins(1,3, 4, 5)P-4], has been proposed to modulate this process, but the literature is not consistent on this point. A recently proposed candidate for the retrograde messenger is an activity extracted from Jurkat cells termed CIF (calcium influx factor), which has many properties consistent with such a messenger. There is also evidence that a GTP-dependent process, possibly involving a Small G protein, is involved in signaling calcium entry and may be involved in either the formation or action of the diffusible messenger for calcium entry. RP PUTNEY, JW (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD AUG PY 1994 VL 5 IS 6 BP 256 EP 260 DI 10.1016/1043-2760(94)P3085-L PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PM598 UT WOS:A1994PM59800006 PM 18407217 ER PT J AU GORSE, GJ FREY, SE PATEL, G NEWMAN, FK BELSHE, RB SCHWARTZ, D CLEMENTS, ML KEEFER, M ROBERTS, N DOLIN, R MCELRATH, J COREY, L GRAHAM, BS WRIGHT, P MATTHEWS, T BOLOGNESI, D WALKER, MC FAST, P FERNIE, BF AF GORSE, GJ FREY, SE PATEL, G NEWMAN, FK BELSHE, RB SCHWARTZ, D CLEMENTS, ML KEEFER, M ROBERTS, N DOLIN, R MCELRATH, J COREY, L GRAHAM, BS WRIGHT, P MATTHEWS, T BOLOGNESI, D WALKER, MC FAST, P FERNIE, BF TI VACCINE-INDUCED ANTIBODIES TO NATIVE AND RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEINS SO VACCINE LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; LIVE VECTOR PRIMING; RGP160 BOOST ID HTLV-III; AIDS VIRUS; NEUTRALIZING ANTIBODIES; NUCLEOTIDE-SEQUENCE; NAIVE ADULTS; GP160; HIV-1; IMMUNOGENICITY; BINDING; CD4 AB The ability of antibody induced by combination vaccination (human immunodeficiency virus type 1 (HIV-1(LAV)) gp160 live recombinant vaccinia virus priming followed by a booster injection with a baculovirus-expressed HIV-1(LAV) recombinant gp160 candidate vaccine) to bind to native and recombinant HIV-1 envelope glycoproteins was measured in 12 uninfected healthy adult volunteers. By using a flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to native envelope glycoprotein expressed by target cells infected with HIV-1(IIIB) (infected-cell FIFA), sera from ten of 12 vaccinees before the rgp160 booster injection were positive, and all vaccinees were positive at higher levels after the rgp160 boost. Evidence for cross-reacting antibody to HIV-1(MN), HIV-1(RF) and HIV-1(CC) expressed on infected cells was also present after the rgp160 booster injection. High titres of anti-rgp160 antibody were also measured in an enzyme-linked immunosorbent assay after the boost. None of the sera obtained immediately prior to the rgp160 booster injection, but all sera drawn after the boost, reacted with recombinant gp160 antigen bound to uninfected cell surfaces. The high anti-gp160 binding activity in these assays, the concomitant presence of positivity in infected-cell and rgp160-coated cell FIFA assays, and high anti-rgp160 antibody titre by ELISA in sera from recipients of this prime-boost vaccination regimen suggest that the live vector priming and rgp160 boosting strategy should be pursued in HIV-1 vaccine development. C1 ST LOUIS DEPT VET AFFAIRS MED CTR,ST LOUIS,MO 63106. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY. UNIV WASHINGTON,SEATTLE,WA 98195. VANDERBILT UNIV,NASHVILLE,TN. DUKE UNIV,DURHAM,NC. NIAID,BETHESDA,MD 20892. GEORGETOWN UNIV,ROCKVILLE,MD. RP GORSE, GJ (reprint author), ST LOUIS UNIV,SCH MED,DIV INFECT DIS,3635 VISTA AVE,FDT-8N,POB 15250,ST LOUIS,MO 63110, USA. FU NIAID NIH HHS [N01-AI-05064] NR 26 TC 20 Z9 20 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1994 VL 12 IS 10 BP 912 EP 918 DI 10.1016/0264-410X(94)90034-5 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NW195 UT WOS:A1994NW19500009 PM 7975833 ER PT J AU SUTTER, G WYATT, LS FOLEY, PL BENNINK, JR MOSS, B AF SUTTER, G WYATT, LS FOLEY, PL BENNINK, JR MOSS, B TI A RECOMBINANT VECTOR DERIVED FROM THE HOST RANGE-RESTRICTED AND HIGHLY ATTENUATED MVA STRAIN OF VACCINIA VIRUS STIMULATES PROTECTIVE IMMUNITY IN MICE TO INFLUENZA-VIRUS SO VACCINE LA English DT Article DE INFLUENZA VIRUS; VACCINIA VIRUS; MVA STRAIN; HOST-RANGE RESTRICTION ID DOMINANT SELECTION; HEMAGGLUTININ; NUCLEOPROTEIN; IMMUNIZATION; GENES AB The immunogenicity of a recombinant vir us derived from modified vaccinia virus Ankara (MVA), a host range-restricted highly attenuated and safety-tested strain, was investigated. Plasmid transfer vectors that provide strong synthetic early/late promoters for the simultaneous expression of two genes as well as a transient or stable selectable marker and flanking sequences for homologous recombination with the MVA genome were constructed. A recombinant MVA containing influenza virus haemagglutinin and nucleoprotein genes was isolated in avian cells and shown to express both proteins efficiently upon infection of human or mouse cells in which abortive replication occurs. Mice, inoculated by various routes with recombinant MVA, produced antibody and cytotoxic T-lymphocyte responses to influenza virus proteins and were protected against a lethal influenza virus challenge as effectively as mice immunized with a recombinant derived from the replication-competent WR strain of vaccinia virus. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 28 TC 214 Z9 218 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1994 VL 12 IS 11 BP 1032 EP 1040 DI 10.1016/0264-410X(94)90341-7 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PA803 UT WOS:A1994PA80300014 PM 7975844 ER PT J AU DUMM, CLAG ATWATER, I EPSTEIN, PN GAGLIARDINO, JJ AF DUMM, CLAG ATWATER, I EPSTEIN, PN GAGLIARDINO, JJ TI QUANTITATIVE IMMUNOCYTOCHEMICAL STUDY OF ISLET-CELL POPULATIONS IN DIABETIC CALMODULIN-TRANSGENIC MICE SO VIRCHOWS ARCHIV LA English DT Article DE PANCREATIC ISLET CELLS; QUANTITATIVE IMMUNOCYTOCHEMISTRY; TRANSGENIC MICE; EXPERIMENTAL DIABETES ID PANCREATIC-ISLETS; BETA-CELL; RAT AB The present study describes the changes in the endocrine pancreas of severely diabetic calmodulin-transgenic mice using light microscopic immunocytochemical and morphometric techniques. A marked reduction in the number and volume of islets, together with distortion of their normal architecture, was found in diabetic mice. In addition, the volume density of both endocrine tissue and B-cells was decreased. An irregular distribution of non-B-cells was also observed in diabetic animals. The volume density and the percentage of A-cells appeared increased. However, when quantified per area unit, the number of all the islet cell types diminished, although only the decrease in B-cell number was statistically significant. The decrease in B-cell mass might account for the diabetic state developed in this animal model. C1 NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. UNIV N DAKOTA, DEPT PHARMACOL & TOXICOL, GRAND FORKS, ND 58203 USA. RP DUMM, CLAG (reprint author), NATL UNIV LA PLATA, FAC CIENCIAS EXACTAS, CONICET, UNLP, CTR ENDOCRINOL EXPTL & APLICADA, RA-1900 LA PLATA, ARGENTINA. NR 19 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD AUG PY 1994 VL 425 IS 1 BP 73 EP 77 PG 5 WC Pathology SC Pathology GA PJ638 UT WOS:A1994PJ63800010 ER PT J AU ANTONI, BA RABSON, AB KINTER, A BODKIN, M POLI, G AF ANTONI, BA RABSON, AB KINTER, A BODKIN, M POLI, G TI NF-KAPPA-B-DEPENDENT AND NF-KAPPA-B-INDEPENDENT PATHWAYS OF HIV ACTIVATION IN A CHRONICALLY INFECTED T-CELL LINE SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; IMMUNODEFICIENCY-VIRUS TYPE-1; TUMOR NECROSIS FACTOR; HERPES-SIMPLEX VIRUS; SODIUM-BUTYRATE; HEXAMETHYLENE BISACETAMIDE; GENE-EXPRESSION; IL-2 PRODUCTION; VIRAL-RNA; INDUCTION AB J Delta K cells were isolated as a chronically infected survivor cell line, following infection of Jurkat CD4+ T cells with dl-NF, a mutated strain of human immunodeficiency Virus type 1 (HIV-I) containing a deletion of the long terminal repeat (LTR) NF-KB sites. J Delta K cells exhibited very low levels of constitutive HIV production. HIV-1 expression was activated from J Delta K cells by treatment with phorbol myristate acetate (PMA), sodium butyrate (NaB), or hexamethylene bisacetamide (HMBA), but not tumor necrosis factor alpha (TNF-alpha), confirming the role of NF-KB in mediating TNF-alpha induction of HIV transcription. The strong induction of HIV expression by NaB or HMBA in J Delta K cells clearly demonstrates the existence of NF-kB-independent mechanisms of HIV activation in chronically infected cells. J Delta K cells may provide a useful model for characterizing NF-kB-independent transcriptional activation of the HIV LTR. (C) 1994 Academic Press, Inc. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. IST SCI SAN RAFFAELE,DIBIT,AIDS IMMUNOPATHOGENESIS UNIT,I-20127 MILAN,ITALY. FU NCI NIH HHS [CA55487]; NIAID NIH HHS [AI30901] NR 52 TC 53 Z9 55 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1994 VL 202 IS 2 BP 684 EP 694 DI 10.1006/viro.1994.1390 PG 11 WC Virology SC Virology GA NY181 UT WOS:A1994NY18100017 PM 7913275 ER PT J AU LANGLEY, RJ HIRSCH, VM OBRIEN, SJ ADGERJOHNSON, D GOEKEN, RM OLMSTED, RA AF LANGLEY, RJ HIRSCH, VM OBRIEN, SJ ADGERJOHNSON, D GOEKEN, RM OLMSTED, RA TI NUCLEOTIDE-SEQUENCE ANALYSIS OF PUMA LENTIVIRUS (PLV-14) - GENOMIC ORGANIZATION AND RELATIONSHIP TO OTHER LENTIVIRUSES SO VIROLOGY LA English DT Article ID FELINE IMMUNODEFICIENCY VIRUS; INFECTIOUS-ANEMIA VIRUS; AFRICAN-GREEN MONKEYS; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; SEROEPIDEMIOLOGIC SURVEY; RETROVIRUS INFECTIONS; CERCOCEBUS-ATYS; NUCLEIC-ACID; PROTEINS AB The complete nucleotide sequence of an isolate of puma lentivirus (PLV-14) was obtained by an inverse polymerase chain reaction (I-PCR) technique and confirmed by conventional PCR. Both methods were used to amplify overlapping regions of proviral DNA, for cloning and sequencing, from genomic DNA isolated from PLV-14 infected Florida puma (Felis concolor coryi) peripheral blood mononuclear cells (PBMC). The provirus has a total length of 9100 nucleotides and the genomic organization of presumed protein coding regions are similar to those seen in other members of the lentivirus family, i.e., three large open reading frames gag, po(, and env as well as smaller intergenic regions that apparently encode regulatory proteins vif and 3' rev by positional and sequence similarity to those seen in other lentiviruses. Two additional open reading frames were identified in the env region and their function (if any) is unknown. The length of the PLV-14 long terminal repeat (LTR) was found to be shorter than the LTRs of feline immunodeficiency virus (FIV). The sequence homology between PLV-14 and other lentiviruses demonstrates that PLV-14 is most closely related to FIV from domestic cats. However, the extent of sequence divergence of each retroviral gene segment is large (e.g., percentage sequence similarity between FIV and PLV-14 env is 8% amino acid and 37% nucleotide similarity), indicating relatively ancient divergence of these feline lentiviral genomes. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UPJOHN CO,UPJOHN LABS,KALAMAZOO,MI 49001. RP LANGLEY, RJ (reprint author), NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [N01-AI-72623] NR 53 TC 34 Z9 34 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1994 VL 202 IS 2 BP 853 EP 864 DI 10.1006/viro.1994.1407 PG 12 WC Virology SC Virology GA NY181 UT WOS:A1994NY18100034 PM 8030248 ER PT J AU BRUGGEMAN, LA THOMSON, MM NELSON, PJ KOPP, JB RAPPAPORT, J KLOTMAN, PE KLOTMAN, ME AF BRUGGEMAN, LA THOMSON, MM NELSON, PJ KOPP, JB RAPPAPORT, J KLOTMAN, PE KLOTMAN, ME TI PATTERNS OF HIV-1 MESSENGER-RNA EXPRESSION IN TRANSGENIC MICE ARE TISSUE-DEPENDENT SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REV-RESPONSE ELEMENT; VIRAL MESSENGER-RNA; GENE-EXPRESSION; HTLV-III; TARGET SEQUENCE; TYPE-1 REV; SECONDARY STRUCTURE; ACTIVATION DOMAIN; PROTEIN AB To explore tissue-specific factors that may be important in HIV-1 transcriptional and post-transcriptional regulation, we examined a transgenic mouse model containing a mutant provirus deleted in the gag and pol region. The level of transgene expression was tissue-dependant. Skin, muscle, and tail consistently expressed the transgene abundantly; intestine, kidney, and thymus exhibited variable but generally low levels of expression; while liver expression was undetectable by Northern analysis. Individual mRNAs within the family of singly and multiply spliced messages were determined by reverse transcription (rt) of RNA samples from mouse tissues, polymerase chain reaction (PCR) amplification, and Southern hybridization with exon-specific probes. The exact percentage of Tat-coding mRNA that was multiply spliced was also determined by competitive rtPCR. When 2-, 4-, or 7-kb (full-length) mRNA species were calculated as a percentage of the total mRNA, two phenotypes of distribution were detected. Lymphoid tissue (thymus and spleen) and kidney had significantly greater amounts of unspliced message (P<0.001) regardless of the level of expression. All other tissues expressed the multiply spliced messages encoding Tat, Rev, and Nef predominantly. Furthermore, utilization of the three major second exon splice acceptor sites for tat, rev, and nef was the same in transgenic mice as has been demonstrated in human cells but the splice acceptor site for the vpu/env was different in murine tissue. The marked tissue-dependent patterns of HIV mRNA expression suggest a potential mechanism for the organ-specific manifestations of AIDS. (C) 1994 Academic Press, Inc. C1 NCI,NIDR,LOM,TUMOR CELL BIOL,VIRAL PATHOGENESIS UNIT,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016 NR 58 TC 24 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1994 VL 202 IS 2 BP 940 EP 948 DI 10.1006/viro.1994.1416 PG 9 WC Virology SC Virology GA NY181 UT WOS:A1994NY18100043 PM 7518165 ER PT J AU JOHNSTONE, PAS SPRAGUE, M DELUCA, AM BACHER, JD HAMPSHIRE, VA TERRILL, RE KINSELLA, TJ SINDELAR, WF AF JOHNSTONE, PAS SPRAGUE, M DELUCA, AM BACHER, JD HAMPSHIRE, VA TERRILL, RE KINSELLA, TJ SINDELAR, WF TI EFFECTS OF INTRAOPERATIVE RADIOTHERAPY ON VASCULAR GRAFTS IN A CANINE MODEL SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE ANIMALS MODELS; CANINE; INTRAOPERATIVE RADIOTHERAPY; NORMAL TISSUE TOLERANCE; VASCULAR GRAFTS ID RADIATION-THERAPY; VENA-CAVA; TOLERANCE; RETROPERITONEAL; IRRADIATION; IORT; AORTA AB Purpose: The effects of intraoperative radiotherapy +/- external beam radiotherapy on prosthetic vascular grafts were investigated in a canine model. Methods and Materials: In 1986 and 1987, 30 adult beagles underwent laparotomy with transection and segmental resection of the infrarenal aorta followed by immediate reconstruction with a prosthetic graft. Intraoperative radiotherapy at varying doses from 0-30 Gy was then administered to all animals. Half of the dogs received 36 Gy external beam radiotherapy in 10 fractions postoperatively. Animals were sacrificed and necropsied at predetermined intervals and as clinically indicated to assess early (less than or equal to 6 months) and late (> 6 months) effects to the vascular graft and surrounding normal tissue. Results: Histopathologic analyses of irradiated vascular structures were performed and correlations were made with the clinical outcome. The most frequent early clinical toxicity was graft thrombosis, occurring in 7 of 10 animals followed for less than or equal to 6 months. Early graft thrombus formation appeared unrelated to radiotherapy dose and probably represented a technical surgical complication. Anastomotic stenosis of varying severity occurred in most animals followed > 6 months. Late (> 6 months) graft stenosis was correlated with intraoperative radiotherapy dose. At less than or equal to 20 Gy of intraoperative irradiation, 3 of 14 animals developed late graft occlusion; at > 25 Gy, five of six animals developed late occlusion. On histopathologic review, increasing intraoperative dose and increasing total radiotherapy dose (intraoperative + external beam) appeared to correspond with increasing severity of graft changes seen after 6 months of follow-up. Conclusions: Thrombus formation is a frequent early complication of vascular graft placement of the infrarenal aorta in our beagle dog model. Intraoperative doses up to 20 Gy appear to contribute minimally to late graft occlusion, while doses greater than or equal to 25 Gy contribute to late occlusion with high likelihood. Both intraoperative dose and total radiotherapy dose correlated with late graft occlusion, and with histopathologic changes in the graft and anastomoses. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,OFF LAB ANIM SCI,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP JOHNSTONE, PAS (reprint author), USN,CTR MED,DIV RADIAT ONCOL,SAN DIEGO,CA 92134, USA. NR 22 TC 18 Z9 18 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 JUL 30 PY 1994 VL 29 IS 5 BP 1015 EP 1025 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PE338 UT WOS:A1994PE33800012 PM 8083070 ER PT J AU KROUMPOUZOS, G URABE, K KOBAYASHI, T SAKAI, C HEARING, VJ AF KROUMPOUZOS, G URABE, K KOBAYASHI, T SAKAI, C HEARING, VJ TI FUNCTIONAL-ANALYSIS OF THE SLATY GENE-PRODUCT (TRP2) AS DOPACHROME TAUTOMERASE AND THE EFFECT OF A POINT MUTATION ON ITS CATALYTIC FUNCTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TYROSINASE-RELATED PROTEIN; 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID; MAMMALIAN MELANOGENESIS; MOUSE TYROSINASE; ALBINO MUTATION; METAL-IONS; MELANIN; REARRANGEMENT; PURIFICATION; MELANOCYTES AB Slaty (slt), an autosomal recessive mutation that arose in YZ57/Ch mice, results in the dilution of coat color and premature hair loss. Recently, a gene encoding a homologue of the melanogenic enzyme tyrosinase (termed tyrosinase related protein 2 or TRP2) was cloned and was subsequently mapped to the slaty locus on chromosome 14. TRP2 was shown to function in melanogenesis as DOPAchrome tautomerase by means of the catalytic activity of the immunopurified protein and in slaty mutant skin samples. In this study, we generated an expression vector of a murine TRP2 encoding cDNA and are able to confirm its activity as DOPAchrome tautomerase. We further demonstrate that the slaty mutation dramatically decreases the catalytic function of the protein. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. OI Kroumpouzos, George/0000-0002-5915-4640 NR 38 TC 41 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 29 PY 1994 VL 202 IS 2 BP 1060 EP 1068 DI 10.1006/bbrc.1994.2036 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NZ240 UT WOS:A1994NZ24000058 PM 8048919 ER PT J AU LEE, CC YAMADA, KM AF LEE, CC YAMADA, KM TI IDENTIFICATION OF A NOVEL TYPE OF ALTERNATIVE SPLICING OF A TYROSINE KINASE RECEPTOR - JUXTAMEMBRANE DELETION OF THE C-MET PROTEIN-KINASE-C SERINE PHOSPHORYLATION REGULATORY SITE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; EGF RECEPTOR; ONCOGENE AB We have detected a novel type of structural variant of the tyrosine kinase receptor for c-met, also known as the hepatocyte growth factor receptor, in mouse tissues. The cDNA of the variant transcript of c-met lacks 141 base pairs, which predicts an in-frame deletion of 47 amino acids in the juxtamembrane region of the cytoplasmic domain. Sequence analysis of genomic DNA containing the c-net locus revealed that the absence of a discrete exon is responsible for this 141-base pair deletion and that alternative splicing leads to production of two forms of transcript. These two forms of transcript are designated as c-met(sm) (for small) and c-met(lg) (for large) to distinguish the absence or presence of the 141-base pair segment, respectively. The c-met(sm) variant is present in adult mouse tissues including kidney, liver, and brain as well as in 9-10-day-old embryos. In all cases, expression of c-met(sm) was lower than that of the normal transcript, c-met(lg). An antiserum against mouse c-Met protein immunoprecipitated corresponding protein forms of similar to 152 and similar to 145 kDa from whole kidney lysate under reducing conditions. The size difference of similar to 7 kDa between these isoforms corresponds to the predicted difference of 47 amino acids, The presence of this shorter variant transcript and its corresponding protein isoform in a variety of normal tissues suggests a physiological role. The deleted region in the cytoplasmic domain of c-met(sm) contains a sequence motif ((S) under bar(985)A (R) under bar S) for protein kinase C phosphorylation that has recently been shown to play a key role in the down-regulation of hepatocyte growth factor receptor kinase activity. The identification of this novel isoform, c-met(sm), demonstrates that a tyrosine kinase receptor can achieve additional diversity by alternative splicing at a key regulatory site in its cytoplasmic domain. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 18 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 29 PY 1994 VL 269 IS 30 BP 19457 EP 19461 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY332 UT WOS:A1994NY33200041 PM 7518457 ER PT J AU SWAIM, WD MINOGUCHI, K OLIVER, C HAMAWY, MM KIHARA, H STEPHAN, V BERENSTEIN, EH SIRAGANIAN, RP AF SWAIM, WD MINOGUCHI, K OLIVER, C HAMAWY, MM KIHARA, H STEPHAN, V BERENSTEIN, EH SIRAGANIAN, RP TI THE ANTIGANGLIOSIDE MONOCLONAL-ANTIBODY AA4 INDUCES PROTEIN-TYROSINE PHOSPHORYLATIONS, BUT NOT DEGRANULATION, IN RAT BASOPHILIC LEUKEMIA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; AFFINITY IGE RECEPTOR; FC-EPSILON-RI; IMMUNOGLOBULIN-E RECEPTORS; MAST-CELLS; SIGNAL TRANSDUCTION; HISTAMINE-RELEASE; PHOSPHOLIPASE C-GAMMA-1; MEDIATED MODULATION; KINASE-ACTIVITY AB The monoclonal antibody AA4 (mAb AA4) recognizes novel alpha-galactosyl derivatives of G(D1b) on rat basophilic leukemia (RBL-2H3) cells. The binding of mAb AA4 induced protein tyrosine phosphorylations without histamine release. Several of the same proteins including Fc epsilon RI beta, Fc epsilon RI gamma, p72(syk), and phospholipase C-gamma 1 were tyrosine-phosphorylated by mAb AA4 binding and by the activation of the high affinity IgE receptor, Fc epsilon RI. There was also activation of the p53/56(lym) and p72(syk) protein-tyrosine kinases, but compared to direct Fc epsilon RI activation, mAb AA4 did not result in increased tyrosine phosphorylation of pp105-115 or pp125(FAK), and the receptor subunits (Fc epsilon RI beta and Fc epsilon RI gamma) were more heavily phosphorylated. Furthermore, the time course of the phosphorylations with mAb AA4 was slower than that induced by Fc epsilon RI aggregation. By immunofluorescence, the tyrosine-phosphorylated proteins after mAb AA4 stimulation were localized in patches at the cell membrane and in areas of cell-cell contact, whereas after Fc epsilon RI activation, there was a reticular cytoplasmic pattern. There were no protein tyrosine phosphorylations either when Fc epsilon RI was saturated with IgE or when F(ab')(2) fragments of mAb AA4 were used, although the F(ab')(2) fragments still induced morphological changes. There was also coprecipitation of the beta and gamma subunits of Fc epsilon RI with the anti-ganglioside antibody. These data strongly suggest the involvement of Fc epsilon RI in the antiganglioside-induced protein tyrosine phosphorylations. Moreover, phosphorylations of these proteins including the beta and gamma chains of Fc epsilon RI and activation of p53/56(lyn) and p72(syk) did not result in histamine release. RP SWAIM, WD (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 65 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 29 PY 1994 VL 269 IS 30 BP 19466 EP 19473 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY332 UT WOS:A1994NY33200043 PM 8034715 ER PT J AU ZHOU, DJ CAM, LL LAUGHTON, CA KORZEKWA, KR CHEN, S AF ZHOU, DJ CAM, LL LAUGHTON, CA KORZEKWA, KR CHEN, S TI MUTAGENESIS STUDY AT A POSTULATED HYDROPHOBIC REGION NEAR THE ACTIVE-SITE OF AROMATASE CYTOCHROME-P450 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIRECTED MUTAGENESIS; INTRATUMORAL AROMATASE; CRYSTAL-STRUCTURE; BREAST; INHIBITORS; SYSTEM; EXPRESSION; ESTROGEN; POTENT AB Aromatase, a cytochrome P450, catalyzes three consecutive hydroxylation reactions converting C19 androgens to aromatic C18 estrogenic steroids. On the basis of a recent computer modeling of the active site of aromatase, a hydrophobic pocket, thought to be important for the binding of some aromatase inhibitors, was predicted to extend roughly in the plane of the steroid substrate, from the position that would be occupied by its C4 and C7 atoms. Four mutants, G121A, I125N, F235N, and I474F, were generated to test this model. Although the mutagenesis results have shown that the current model for the active site of aromatase almost certainly contains a number of errors, the results are in general very satisfactory in that they suggest how the model should be altered by local realignments of the aromatase sequence with that of cytochrome P450(cam). Among the mutants, I474F is the most interesting one. Its K-m value for androstenedione was found to be lower than the wild type enzyme, and the kinetic analysis exhibited a substrate inhibition-like kinetic profile through an ''in-cell'' assay. In addition, this mutation reduces the binding affinity of an aromatase inhibitor, 4-hydroxyandrostenedione, and increases the binding affinity of two aromatase inhibitors, aminoglutethimide and CGS 16949. This study demonstrates a useful approach, by a combination of computer modeling, site-directed mutagenesis, and inhibitor binding studies, to examine the structure of the active site of aromatase and the binding nature of various aromatase inhibitors. C1 BECKMAN RES INST CITY HOPE,DIV IMMUNOL,DUARTE,CA 91010. INST CANC RES,CRC,BIOMOLEC STRUCT UNIT,SUTTON SM2 5NG,SURREY,ENGLAND. NIH,BETHESDA,MD 20892. RI Laughton, Charles/E-5667-2010 OI Laughton, Charles/0000-0003-4090-3960 FU NCI NIH HHS [CA33572, CA44735] NR 28 TC 47 Z9 47 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 29 PY 1994 VL 269 IS 30 BP 19501 EP 19508 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY332 UT WOS:A1994NY33200048 PM 8034720 ER PT J AU ARECES, LB KAZANIETZ, MG BLUMBERG, PM AF ARECES, LB KAZANIETZ, MG BLUMBERG, PM TI CLOSE SIMILARITY OF BACULOVIRUS-EXPRESSED N-CHIMAERIN AND PROTEIN-KINASE C-ALPHA AS PHORBOL ESTER RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; CD-1 MOUSE SKIN; NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; POTENT TUMOR PROMOTERS; 12,13-DIBUTYRATE BINDING; 12-MYRISTATE 13-ACETATE; CAENORHABDITIS-ELEGANS; CALPHOSTIN-C; UNC-13 GENE; INHIBITORS AB n-Chimaerin is a recently described phorbol ester receptor that shares homology in its N-terminal region with the cysteine-rich zinc finger domain of protein kinase C. We have expressed n-chimaerin in insect cells using the baculovirus system and have used the isolated, recombinant n-chimaerin to characterize phorbol ester binding and structure-activity relations, lipid requirements, and inhibitor sensitivity. We find that n-chimaerin expressed in the baculovirus system bound [H-3]phorbol 12,13-dibutyrate with high affinity (0.17 +/- 0.01 nM). Although having only a single cysteine-rich zinc finger region compared to two for protein kinase C, n-chimaerin thus closely resembled protein kinase C alpha. n-chimaerin was likewise virtually indistinguishable from protein kinase C alpha in phorbol ester structure activity relations, in phospholipid requirements, and in inhibition of binding by sphingosine and calphostin C, protein kinase C inhibitors acting on the regulatory domain. We conclude that a number of typical approaches used to implicate protein kinase C in biological function in cells do not discriminate between the n-chimaerin and protein kinase C classes of phorbol ester receptors. C1 NCI,MOLEC MECHANISMS TUMOR PROMOT SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 41 TC 74 Z9 74 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 29 PY 1994 VL 269 IS 30 BP 19553 EP 19558 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY332 UT WOS:A1994NY33200055 PM 7518459 ER PT J AU DZAMBA, BJ BULTMANN, H AKIYAMA, SK PETERS, DM AF DZAMBA, BJ BULTMANN, H AKIYAMA, SK PETERS, DM TI SUBSTRATE-SPECIFIC BINDING OF THE AMINO-TERMINUS OF FIBRONECTIN TO AN INTEGRIN COMPLEX IN FOCAL ADHESIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN FIBROBLAST-CULTURES; MATRIX ASSEMBLY DOMAIN; CELL-ADHESION; PLASMA FIBRONECTIN; CONFORMATIONAL-CHANGES; MONOCLONAL-ANTIBODIES; BIOLOGICAL-ACTIVITY; ENDOTHELIAL-CELLS; RECEPTOR; ALPHA-5-BETA-1 AB The assembly of fibronectin fibrils involves the amino terminal and cell adhesion domains of fibronectin as well as alpha(5) beta(1) integrins. Efficient binding of biotinylated or radioiodinated 70-kDa amino-terminal fragments occurred only if fibroblasts were plated on fibronectin or on 180- or 85-kDa cell adhesion fragments of fibronectin. On an 11.5-kDa fragment of fibronectin that included the Arg-Gly-Asp (RGD) sequence, but not the synergy site, binding was reduced 50-fold. Conformation of the 180-kDa fragment was important for direct binding interactions with the amino terminus of fibronectin. No binding was seen if cells were plated on type I collagen, vitronectin, RGD peptides or antibodies to alpha(5) beta(1) inte grins. High affinity interactions between invasin and alpha(5) beta(1) integrin promoted low levels of binding. Monoclonal antibodies that blocked the function of either the RGD or the synergy site inhibited binding of I-125-labeled 70-kDa fragments to cells by similar to 60%. By fluorescence and interference reflection microscopy, biotinylated 70 kDa fragments were shown to co-localize with alpha(5) beta(1) integrins in focal adhesions. We propose that cell-mediated binding of the amino terminus of fibronectin involves interactions with both fibronectin and its alpha(5) beta(1) integrin receptor in an activated complex. C1 UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI 53706. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [RR570]; NEI NIH HHS [EY08540]; NIGMS NIH HHS [GM47221] NR 52 TC 56 Z9 56 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 29 PY 1994 VL 269 IS 30 BP 19646 EP 19652 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY332 UT WOS:A1994NY33200069 PM 7518462 ER PT J AU WARBURG, A SARAIVA, E LANZARO, GC TITUS, RG NEVA, F AF WARBURG, A SARAIVA, E LANZARO, GC TITUS, RG NEVA, F TI SALIVA OF LUTZOMYIA-LONGIPALPIS SIBLING SPECIES DIFFERS IN ITS COMPOSITION AND CAPACITY TO ENHANCE LEISHMANIASIS SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID SAND FLY SALIVA; CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; VASODILATORY PEPTIDE; MACROPHAGE FUNCTION; CAUSATIVE AGENT; NORTH TUNISIA; INFECTION; INFANTUM; BRAZIL AB Leishmania donovani chagasi parasites, transmitted by sandflies of the Lutzomyia longipalpis species complex, normally cause visceral leishmaniasis. However, in Central America infections frequently result in cutaneous disease. We undertook experiments to investigate the possible influence of sandfly saliva on the course of infection. Erythemas caused by feeding sandflies correlated well with the levels of the erythema-inducing peptide, maxadilan, in their saliva. Saliva of Brazilian flies was the most potent, that of Colombian flies less so, and Costa Rican saliva had very little maxadilan and lacked activity. Nucleotide sequence differences in the maxadilan gene of the three species were detected by 'single strand conformational polymorphism' electrophoresis. Leishmania infections proliferated fastest when coinjected with the saliva of Costa Rican flies. Brazilian flies had less influence, and Colombian flies only a slight effect. Thus Costa Rican Lutzomyia longipalpis, vectors of non-ulcerative cutaneous disease, have very low vasodilatory activity and very little maxadilan, but their saliva strongly enhances cutaneous proliferation of Leishmania infections. Conversely, flies from Colombia and Brazil, vectors of visceral disease, have more maxadilan, but exacerbate cutaneous infections to a lesser degree. These coincidental observations suggest that species of Lutzomyia longipalpis differ in their propensity to modulate the pathology of the disease they transmit. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT PARASITOL,IL-91010 JERUSALEM,ISRAEL. HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. RP WARBURG, A (reprint author), NIAID,MALARIA RES LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI 27511] NR 37 TC 107 Z9 108 U1 0 U2 4 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD JUL 29 PY 1994 VL 345 IS 1312 BP 223 EP 230 DI 10.1098/rstb.1994.0097 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA PA856 UT WOS:A1994PA85600005 PM 7972360 ER PT J AU VILENSKY, B HAVLIN, S TAITELBAUM, H WEISS, GH AF VILENSKY, B HAVLIN, S TAITELBAUM, H WEISS, GH TI MOMENTUM EFFECTS IN REACTION-DIFFUSION SYSTEMS SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID INITIALLY SEPARATED REACTANTS; REACTION FRONT DYNAMICS; REACTION-KINETICS; RANDOM-WALK; HEAT WAVES; A+B->C; SEGREGATION; FLUCTUATIONS AB The standard formulation of reaction-diffusion equations assumes that the reacting particles undergo Brownian motion. We generalize the consequent formalism by incorporating a rudimentary model of momentum effects, based on a persistent random-walk model. This formulation is used to study some properties of the reaction A + B --> C with the reactant species initially separated in space. It is shown that the change in dynamics introduces an additional short-time scaling regime in the behavior of the reaction rate. C1 BAR ILAN UNIV, DEPT PHYS, IL-52100 RAMAT GAN, ISRAEL. NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NR 37 TC 8 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUL 28 PY 1994 VL 98 IS 30 BP 7325 EP 7328 DI 10.1021/j100081a015 PG 4 WC Chemistry, Physical SC Chemistry GA NZ993 UT WOS:A1994NZ99300016 ER PT J AU FOX, CH HOOVER, S CURRALL, VR BAHRE, HJ COTTLERFOX, M AF FOX, CH HOOVER, S CURRALL, VR BAHRE, HJ COTTLERFOX, M TI HIV IN INFECTED LYMPH-NODES SO NATURE LA English DT Letter C1 FUJI MED SYST,STAMFORD,CT 06912. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP FOX, CH (reprint author), MOLEC HISTOL LAB INC,7605 F AIRPK RD,GAITHERSBURG,MD 20879, USA. NR 8 TC 16 Z9 16 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 28 PY 1994 VL 370 IS 6487 BP 256 EP 256 DI 10.1038/370256a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NZ229 UT WOS:A1994NZ22900037 PM 8035872 ER PT J AU BEZRUKOV, SM VODYANOY, I PARSEGIAN, VA AF BEZRUKOV, SM VODYANOY, I PARSEGIAN, VA TI COUNTING POLYMERS MOVING THROUGH A SINGLE-ION CHANNEL SO NATURE LA English DT Article ID PROBING ALAMETHICIN CHANNELS; WATER-SOLUBLE POLYMERS; MEMBRANES; MODEL AB THE change in conductance of a small electrolyte-filled capillary owing to the passage of sub-micrometre-sized particles has long been used for particle counting and sizing. A commercial device for such measurements, the Coulter counter, is able to detect particles of sizes down to several tenths of a micrometre(1-3). Nuclepore technology (in which pores are etched particle tracks) has extended the lower limit of size detection to 60-nm particles by using a capillary of diameter 0.45 mu m (ref. 4). Here we show that natural channel-forming peptides incorporated into a bilayer lipid membrane can be used to detect the passage of single molecules with gyration radii as small as 5-15 Angstrom. From our experiments with alamethicin pores we infer both the average number and the diffusion coefficients of poly(ethylene glycol) molecules in the pore. Our approach provides a means of observing the statistics and mechanics of flexible polymers moving within the confines of precisely defined single-molecule structures. C1 NIH,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892. RUSSIAN ACAD SCI,INST NUCL PHYS,ST PETERSBURG 188350,RUSSIA. OFF NAVAL RES,ARLINGTON,VA 22217. RP BEZRUKOV, SM (reprint author), NIDDK,DIV INTRAMURAL RES,BETHESDA,MD 20892, USA. NR 20 TC 259 Z9 261 U1 7 U2 42 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 28 PY 1994 VL 370 IS 6487 BP 279 EP 281 DI 10.1038/370279a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NZ229 UT WOS:A1994NZ22900058 PM 7518571 ER PT J AU SHAHAR, E FOLSOM, AR MELNICK, SL TOCKMAN, MS COMSTOCK, GW GENNARO, V HIGGINS, MW SORLIE, PD KO, WJ SZKLO, M AF SHAHAR, E FOLSOM, AR MELNICK, SL TOCKMAN, MS COMSTOCK, GW GENNARO, V HIGGINS, MW SORLIE, PD KO, WJ SZKLO, M TI DIETARY N-3 POLYUNSATURATED FATTY-ACIDS AND SMOKING-RELATED CHRONIC OBSTRUCTIVE PULMONARY-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CIGARETTE-SMOKING; FISH-OIL; SUPPLEMENTATION; EMPHYSEMA; NEUTROPHIL; GENERATION; INVITRO; HEALTH AB Background. Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions. Methods. We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects). Results. After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P<0.001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007). Conclusions. A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. IST NAZL RIC CANC,ENVIRONM EPIDEMIOL SERV,I-16132 GENOA,ITALY. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,CHAPEL HILL,NC. RP SHAHAR, E (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55022] NR 30 TC 124 Z9 127 U1 1 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 28 PY 1994 VL 331 IS 4 BP 228 EP 233 DI 10.1056/NEJM199407283310403 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NY335 UT WOS:A1994NY33500003 PM 8015569 ER PT J AU ROGAWSKI, MA AF ROGAWSKI, MA TI RILUZOLE IN AMYOTROPHIC-LATERAL-SCLEROSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP ROGAWSKI, MA (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 28 PY 1994 VL 331 IS 4 BP 273 EP 273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NY335 UT WOS:A1994NY33500016 PM 8015581 ER PT J AU HENNINGFIELD, JE KOZLOWSKI, LT BENOWITZ, NL AF HENNINGFIELD, JE KOZLOWSKI, LT BENOWITZ, NL TI A PROPOSAL TO DEVELOP MEANINGFUL LABELING FOR CIGARETTES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID LOW-YIELD CIGARETTES; CARBON-MONOXIDE; NICOTINE; SMOKING; TAR; BLOCKING; EXPOSURE; VENTS C1 PENN STATE UNIV,COLL HLTH & HUMAN DEV,PROGRAM BIOBEHAV HLTH,UNIV PK,PA 16802. UNIV CALIF SAN FRANCISCO,DIV CLIN PHARMACOL & EXPTL THERAPEUT,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. RP HENNINGFIELD, JE (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 20 TC 35 Z9 35 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 27 PY 1994 VL 272 IS 4 BP 312 EP 314 DI 10.1001/jama.272.4.312 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NX806 UT WOS:A1994NX80600035 PM 8028146 ER PT J AU PRASAD, JVNV PARA, KS LUNNEY, EA ORTWINE, DF DUNBAR, JB FERGUSON, D TUMMINO, PJ HUPE, D TAIT, BD DOMAGALA, JM HUMBLET, C BHAT, TN LIU, BS GUERIN, DMA BALDWIN, ET ERICKSON, JW SAWYER, TK AF PRASAD, JVNV PARA, KS LUNNEY, EA ORTWINE, DF DUNBAR, JB FERGUSON, D TUMMINO, PJ HUPE, D TAIT, BD DOMAGALA, JM HUMBLET, C BHAT, TN LIU, BS GUERIN, DMA BALDWIN, ET ERICKSON, JW SAWYER, TK TI NOVEL SERIES OF ACHIRAL, LOW-MOLECULAR-WEIGHT, AND POTENT HIV-1 PROTEASE INHIBITORS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID PROTEINASE C1 WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT BIOCHEM,ANN ARBOR,MI 48106. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RP PRASAD, JVNV (reprint author), WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT CHEM,2800 PLYMOUTH RD,ANN ARBOR,MI 48106, USA. RI Guerin, Diego /N-4486-2014 NR 27 TC 128 Z9 130 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 27 PY 1994 VL 116 IS 15 BP 6989 EP 6990 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NZ547 UT WOS:A1994NZ54700085 ER PT J AU CHYAN, YJ ACKERMAN, S SHEPHERD, NS MCBRIDE, OW WIDEN, SG WILSON, SH WOOD, TG AF CHYAN, YJ ACKERMAN, S SHEPHERD, NS MCBRIDE, OW WIDEN, SG WILSON, SH WOOD, TG TI THE HUMAN DNA-POLYMERASE BETA-GENE STRUCTURE - EVIDENCE OF ALTERNATIVE SPLICING IN GENE-EXPRESSION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PERMEABLE HUMAN-FIBROBLASTS; REPAIR SYNTHESIS; ESCHERICHIA-COLI; CDNA CLONING; HUMAN GENOME; IDENTIFICATION; FRAGMENTS; PROMOTER; CONSERVATION; INHIBITORS AB DNA polymerase beta (beta-pol) is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. Using two human genomic libraries we have cloned the complete human beta-pol gene and determined the organization of the beta-pol coding sequence within the gene. The human beta-pol gene spans 33 kb and contains 14 exons that range from 50 to 233 bp. The 13 introns vary from 96 bp to 6.5 kb. Information derived from this study was used in defining the location of a deletion/insertion type restriction fragment length polymorphism (RFLP) 5' to exon I of the human beta-pol gene. This RFLP was utilized in linkage analysis of DNAs from CEPH families and the results confirm the previous assignment of the human beta-pol gene to chromosome 8 (p12 - p11). Analysis of mRNA from six human cell lines using the polymerase chain reaction showed the expression of two beta-pol transcripts. Sequence analysis revealed that the size difference in these transcripts was due to deletion of the 58 bp sequence encoded by exon II, suggesting that the smaller transcript results from an alternative splicing of the exon II sequence during processing of the beta-pol precursor RNA. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,RECOMBINANT DNA LAB,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77555. DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Wood, Thomas/B-6172-2012 NR 42 TC 30 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1994 VL 22 IS 14 BP 2719 EP 2725 DI 10.1093/nar/22.14.2719 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA874 UT WOS:A1994PA87400001 PM 7914364 ER PT J AU WANG, JTL MARR, TG SHASHA, D SHAPIRO, BA CHIRN, GW AF WANG, JTL MARR, TG SHASHA, D SHAPIRO, BA CHIRN, GW TI DISCOVERING ACTIVE MOTIFS IN SETS OF RELATED PROTEIN SEQUENCES AND USING THEM FOR CLASSIFICATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEIC-ACID SEQUENCES; NUCLEOTIDE-SEQUENCE; PATTERN-RECOGNITION; ESCHERICHIA-COLI; FIND HOMOLOGIES; ALIGNMENT; PROGRAM; CONSENSUS; ALGORITHM; IDENTIFICATION AB We describe a method for discovering active motifs in a set of related protein sequences. The method is an automatic two step process: (1) find candidate motifs in a small sample of the sequences; (2) test whether these motifs are approximately present in all the sequences. To reduce the running time, we develop two optimization heuristics based on statistical estimation and pattern matching techniques. Experimental results obtained by running these algorithms on generated data and functionally related proteins demonstrate the good performance of the presented method compared with visual method of O'Farrell and Leopold. By combining the discovered motifs with an existing fingerprint technique, we develop a protein classifier. When we apply the classifier to the 698 groups of related proteins in the PROSITE catalog, it gives information that is complementary to the BLOCKS protein classifier of Henikoff and Henikoff. Thus, using our classifier in conjunction with theirs, one can obtain high confidence classifications (if BLOCKS and our classifier agree) or suggest a new hypothesis (if the two disagree). C1 COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NYU,COURANT INST MATH SCI,NEW YORK,NY 10012. NCI,DIV CANC BIOL & DIAG,MATH BIOL LAB,IMAGE PROC SECT,FREDERICK,MD 21701. NEW JERSEY INST TECHNOL,DEPT COMP & INFORMAT SCI,NEWARK,NJ 07102. RP WANG, JTL (reprint author), NEW JERSEY INST TECHNOL,DEPT COMP & INFORMAT SCI,NEWARK,NJ 07102, USA. FU NHGRI NIH HHS [1RO1-HG0020301A1] NR 42 TC 30 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1994 VL 22 IS 14 BP 2769 EP 2775 DI 10.1093/nar/22.14.2769 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA874 UT WOS:A1994PA87400008 PM 8052532 ER PT J AU JANKOVIC, M BROUWERS, P VALSECCHI, MG VANVELDHUIZEN, A HUISMAN, J KAMPHUIS, R KINGMA, A MOR, W VANDONGENMELMAN, J FERRONATO, L MANCINI, MA SPINETTA, JJ MASERA, G AF JANKOVIC, M BROUWERS, P VALSECCHI, MG VANVELDHUIZEN, A HUISMAN, J KAMPHUIS, R KINGMA, A MOR, W VANDONGENMELMAN, J FERRONATO, L MANCINI, MA SPINETTA, JJ MASERA, G TI ASSOCIATION OF 1800 CGY CRANIAL IRRADIATION WITH INTELLECTUAL FUNCTION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA SO LANCET LA English DT Article ID LONG-TERM SURVIVORS; CENTRAL NERVOUS-SYSTEM; ACUTE LYMPHOCYTIC-LEUKEMIA; CHILDHOOD LEUKEMIA; COGNITIVE FUNCTION; RADIATION; SEQUELAE; NEUROTOXICITY; METHOTREXATE; PROPHYLAXIS AB Cranial radiation therapy in childhood acute lymphoblastic leukaemia has been associated with adverse neuropsychological effects, such as low intelligence. However, records show that these associations usually occur when the dose of radiation used is 2400 cGy. We investigated whether a lower dose of 1800 cGy had the same adverse effects on long-term survivors and whether high doses of methotrexate but no radiation therapy would have a more beneficial effect. We evaluated 203 children for six years in a multi-centre European study. The patients were divided into two groups: 129 children treated with 1800 cGy of cranial radiation therapy and 74 children who received high-dose methotrexate but no radiation therapy. We used full scale intelligence quotient, verbal, and performance IQ tests to assess the patient's intelligence. We found a significant decline in full scale intelligence quotient in the irradiated group that increased with the length of time from diagnosis. Younger age at diagnosis was associated with lower full scale intelligence quotient in the radiated group. Our results indicate that a radiation dose of 1800 cGy can have negative effects on neurocognitive function and we continue to question the benefit of low-dose cranial radiation therapy. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV MILAN,INST BIOMETRY & MED STAT,I-20122 MILAN,ITALY. UNIV AMSTERDAM,DEPT PAEDIAT,AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,DEPT PSYCHOL MED,AMSTERDAM,NETHERLANDS. LEIDEN UNIV,DEPT PAEDIAT,LEIDEN,NETHERLANDS. UNIV GRONINGEN,9700 AB GRONINGEN,NETHERLANDS. ST ANNA CHILDRENS HOSP,VIENNA,AUSTRIA. UNIV ROTTERDAM,DEPT PAEDIAT,ROTTERDAM,NETHERLANDS. UNIV PADUA,I-35100 PADUA,ITALY. UNIV BOLOGNA,I-40126 BOLOGNA,ITALY. RP JANKOVIC, M (reprint author), UNIV MILAN,S GERARDO HOSP MONZA,DEPT PAEDIAT,VIA DONIZETTI 106,I-20052 MONZA,ITALY. NR 29 TC 132 Z9 133 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 23 PY 1994 VL 344 IS 8917 BP 224 EP 227 DI 10.1016/S0140-6736(94)92997-1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NY060 UT WOS:A1994NY06000009 PM 7913156 ER PT J AU GRIFO, FT AF GRIFO, FT TI PHARMACEUTICALS FROM PLANTS SO LANCET LA English DT Letter RP GRIFO, FT (reprint author), NIH,FOGARTY INT CTR,ICBG PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 23 PY 1994 VL 344 IS 8917 BP 272 EP 273 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NY060 UT WOS:A1994NY06000060 PM 7913192 ER PT J AU BLUML, K MUTSCHLER, E WESS, J AF BLUML, K MUTSCHLER, E WESS, J TI FUNCTIONAL-ROLE IN LIGAND FINDING AND RECEPTOR ACTIVATION OF AN ASPARAGINE RESIDUE PRESENT IN THE 6TH TRANSMEMBRANE DOMAIN OF ALL MUSCARINIC ACETYLCHOLINE-RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; ANTAGONIST BINDING; TYROSINE RESIDUES; MUTATION; M3-MUSCARINIC-RECEPTOR; IDENTIFICATION; HYDROLYSIS; THREONINE AB The molecular mechanisms through which muscarinic receptors are activated upon binding of the neurotransmitter acetylcholine (ACh) are still poorly understood. Classical structure-function relationship studies have previously established that the ACh ester moiety plays a key role in muscarinic receptor recognition and activation. Consistent with this notion, all recently proposed three dimensional muscarinic receptor models predict that an asparagine residue present in transmembrane domain VI of all muscarinic receptors is critically involved in the binding of the ACh ester moiety by means of hydrogen bonding. To test the correctness of this hypothesis, we created several mutant m3 muscarinic receptors in which this residue (Asn(507)) was replaced with alanine, serine, or aspartic acid. Radioligand binding studies with transfected COS-7 cells showed that, in contrast to the predictions made based on molecular modeling studies, all three mutant receptors were able to bind ACh and the structurally related muscarinic agonist, carbachol, with high affinities which differed from the corresponding wild type values by less than 5-fold. However, all three mutations led to dramatic reductions (235-28,300-fold) in binding affinities for certain subclasses of muscarinic antagonists including atropine-like agents and pirenzepine. The m3(Asn(507) --> Ala) and m3(Asn(507) --> Asp) mutant receptors were able to mediate carbachol-induced phosphatidylinositol hydrolysis in a fashion similar to that of the wild type receptor. Interestingly, the m3(Asn(507) --> Ser) mutant receptor displayed about 2-fold increased basal inositol phosphate levels, raising the possibility that it is constitutively active. In conclusion, our data suggest that the asparagine residue present in transmembrane domain VI of all muscarinic receptors is not critical for ACh binding and agonist-induced receptor activation, but plays a key role in the binding of certain subclasses of muscarinic antagonists. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV FRANKFURT,DEPT PHARMACOL,D-60053 FRANKFURT,GERMANY. NR 37 TC 71 Z9 71 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 18870 EP 18876 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700029 PM 8034642 ER PT J AU EFIOK, BJS CHIORINI, JA SAFER, B AF EFIOK, BJS CHIORINI, JA SAFER, B TI A KEY TRANSCRIPTION FACTOR FOR EUKARYOTIC INITIATION FACTOR-2-ALPHA IS STRONGLY HOMOLOGOUS TO DEVELOPMENTAL TRANSCRIPTION FACTORS AND MAY LINK METABOLIC GENES TO CELLULAR GROWTH AND DEVELOPMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; SEA-URCHIN EMBRYO; LEUCINE ZIPPER; REGULATORY FACTORS; SERUM DEPLETION; ACTIVATION; EXPRESSION; SEQUENCE; DOMAINS; TRANSLATION AB In response to growth, metabolic, and other signals, eukaryotic cells regulate protein biosynthesis through post-translational mechanisms which target the alpha subunit of eukaryotic initiation factor-2 (eIF-2 alpha). Previous efforts to study transcriptional mechanisms underlying this regulation identified a novel transcription factor (alpha-Pal) for the eIF-2 alpha gene. To gain insights into the overall biological function of alpha-Pal, we cloned its cDNA. Sequence analysis of the encoded protein reveals that alpha-Pal is a putative bZIP transcription factor. Surprisingly, both the protein sequence and the DNA-recognition site (TGCGCATGCGCA) of this human protein are strongly homologous to those of two evolutionarily distant developmental transcription factors, P3A2 and ewg. Since P3A2 directs territory-specific transcription of muscle genes in sea urchin embryos, and ewg apparently directs transcription of flight muscle and neuronal genes in Drosophila embryos, it is likely that alpha-Pal directs similar gene transcription during human embryo-genesis. In other studies, we also identified genes containing alpha-Pal-binding sequences as those involved in cellular proliferation, or the growth-responsive metabolic pathways, energy transduction, translation, and DNA replication/repair. Such data suggest that alpha-Pal also functions to modulate the transcription of metabolic genes required for cellular growth. C1 NHLBI,MOLEC HEMATOL LAB,PROT & RNA BIOSYNTH SECT,BETHESDA,MD 20892. NR 50 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 18921 EP 18930 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700036 PM 8034649 ER PT J AU CAVENAGH, MM BREINER, M SCHURMANN, A ROSENWALD, AG TERUI, T ZHANG, CJ RANDAZZO, PA ADAMS, M JOOST, HG KAHN, RA AF CAVENAGH, MM BREINER, M SCHURMANN, A ROSENWALD, AG TERUI, T ZHANG, CJ RANDAZZO, PA ADAMS, M JOOST, HG KAHN, RA TI ADP-RIBOSYLATION FACTOR (ARF)-LIKE-3, A NEW MEMBER OF THE ARF FAMILY OF GTP-BINDING PROTEINS CLONED FROM HUMAN AND RAT-TISSUES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENYLATE-CYCLASE; RNA-POLYMERASE; GENES; AMPLIFICATION; DROSOPHILA; EXPRESSION; COFACTOR; BOVINE; BRAIN AB The human and rat homologues of a new member of the ADP-ribosylation factor (ARF) family of 21-kDa GTP-binding proteins, termed Arl3, were identified as an expressed sequence tag (human) and as a product of polymerase chain reaction amplification using degenerate probes derived from conserved sequences in members of the ARF family (rat). Alignments of the full-length open reading frames of the human and rat homologues revealed the encoded proteins to be over 97% identical to each other and 43% identical to human ARF1. Northern blots of mRNA from seven human tissues and four rat tissues revealed the presence of a ubiquitous band of about 1 kilobase in length that hybridized with the corresponding Arl3 probes. A number of human tumor cell lines expressed Arl3, as determined by immunoblotting with an Arl-specific antibody, raised against a peptide derived from the human Arl3 sequence. The level of Arl3 expressed in these cell lines was on the order of 0.01% of total cell protein. Purified recombinant human Arl3 was shown to bind guanine nucleotides but lacks ARF activity and intrinsic or ARF GTPase-activating protein-stimulated GTPase activity. In contrast to ARF proteins, the Arl3 protein has reduced dependence on phospholipids and magnesium for guanine nucleotide exchange. Thus, Arl3 is a ubiquitously expressed GTP-binding protein in the ARF family with distinctive biochemical properties consistent with its having unique, but unknown, role(s) in cell physiology. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. INST GENOM RES,GAITHERSBURG,MD 20878. RHEIN WESTFAL TH AACHEN,FAK MED,INST PHARMAKOL & TOXIKOL,D-52057 AACHEN,GERMANY. RI Joost, Hans-Georg/J-4462-2013 OI Joost, Hans-Georg/0000-0002-5860-606X NR 26 TC 56 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 18937 EP 18942 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700038 PM 8034651 ER PT J AU KIRKEN, RA RUI, H MALABARBA, MG FARRAR, WL AF KIRKEN, RA RUI, H MALABARBA, MG FARRAR, WL TI IDENTIFICATION OF INTERLEUKIN-2 RECEPTOR-ASSOCIATED TYROSINE KINASE P116 AS NOVEL LEUKOCYTE-SPECIFIC JANUS KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-HORMONE RECEPTOR; IL-2 RECEPTOR; GAMMA-CHAIN; FUNCTIONAL COMPONENT; BETA-SUBUNIT; SUPERFAMILY; JAK2; PHOSPHORYLATION; DOMAIN; FAMILY AB Janus tyrosine kinase (JAK) has recently been linked to signal transduction by cytokine receptors of the hematopoietin family. We have recently described a 116-kDa tyrosine kinase (p116) present in interleukin-2 (IL-2) receptor complexes in human YT cells that showed functional characteristics of a JAK kinase. These included receptor association, rapid and transient tyrosine phosphorylation kinetics in response to ligand, and in vitro autophosphorylating tyrosine kinase activity (Kirken, R. A., Rui, H., Evans, G. A., and Farrar, W. L. (1993) J. Biol. Chem. 268, 22765-22770). Here we extend these observations by demonstrating structural homologies between IL-2-modulated p116 and prolactin-modulated JAK2 in the rat T cell line Nb2. These include similar net charge as determined by nonequilibrium pH gradient electrofocusing and related primary structure based upon phosphopeptide mapping of V8 protease-digested hyperphosphorylated proteins. This putative JAK kinase underwent marked tyrosine phosphorylation in response to IL-2, IL-4, and IL-7, lymphoid growth factors that use the common IL-2 receptor gamma-chain, but not in response to prolactin. Furthermore, polyclonal antisera to JAK1, JAK2, or tyrosine kinase 2 did not recognize either rat or human p116. However, we identified the IL-2-modulated p116 as the recently cloned novel leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to the COOH terminus of human L-JAK. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP KIRKEN, RA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 32 TC 62 Z9 62 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 19136 EP 19141 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700066 PM 7518451 ER PT J AU XIAO, RP HOHL, C ALTSCHULD, R JONES, L LIVINGSTON, B ZIMAN, B TANTINI, B LAKATTA, EG AF XIAO, RP HOHL, C ALTSCHULD, R JONES, L LIVINGSTON, B ZIMAN, B TANTINI, B LAKATTA, EG TI BETA(2)-ADRENERGIC RECEPTOR-STIMULATED INCREASE IN CAMP IN RAT-HEART CELLS IS NOT COUPLED TO CHANGES IN CA2+ DYNAMICS, CONTRACTILITY, OR PHOSPHOLAMBAN PHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC STIMULATION; ADENYLATE-CYCLASE STIMULATION; HUMAN VENTRICULAR MYOCARDIUM; CYCLIC-AMP; PROTEIN-KINASE; SARCOPLASMIC-RETICULUM; BETA-2-ADRENERGIC RECEPTORS; INOTROPIC RESPONSES; KITTEN MYOCARDIUM; RIGHT ATRIUM AB Previous studies have Shown that both beta(1)- and beta(2)-adrenergic receptors (AR) are present in rat ventricular myocytes, but stimulation of these receptor subtypes elicits qualitatively different cellular responses (Xiao, R.-P., and Lakatta, E. G. (1993) Circ. Res. 73, 286-300). In the present study, the biochemical mechanism underlying the distinct beta AR subtype actions have been investigated. Although both beta(1)AR and beta(2)AR stimulation increased total cellular cAMP in suspensions of rat ventricular myocytes to a similar extent, the maximum elevation of the membrane bound cAMP by beta(2)AR stimulation was only half of that induced by beta(1)AR stimulation, suggesting that stimulation the beta AR subtypes leads to different compartmentation of cAMP. The effects of beta(1)AR stimulation on Ca2+ transient (indexed by the transient increase in indo-1 fluorescence ration after excitation) and contraction amplitude (measured via photodiode array) and their kinetics closely paralleled the increase in cAMP. In contrast, the increase in both membrane bound and total cAMP content after beta(2)AR stimulation were completely dissociated from the effects of beta(2)AR stimulation to increase the amplitudes of cytosolic Ca2+ transient and contraction. Furthermore, beta(2)AR stimulation did not phosphorylate phospholamban to the same extent as did beta(1)AR stimulation. This finding provides a mechanism for the failure of beta(2)AR stimulation to accelerate the kinetics of the Ca-i(2+) (cytosolic Ca2+) transient and contraction. These results indicate that the effects of beta(2)AR stimulation on Ca-i(2+) transient and contraction are uncoupled from the cAMP production and cAMP-dependent protein phosphorylation and indicate that, in addition to coupling to adenylate cyclase, beta(2)AR stimulation also activates other signal transduction pathway(s) to produce changes in cytosolic Ca2+ and contraction. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. OHIO STATE UNIV,DEPT MED BIOCHEM,COLUMBUS,OH 43210. INDIANA UNIV,SCH MED,KRANNERT INST CARDIOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. UNIV BOLOGNA,DEPT BIOCHEM,I-40100 BOLOGNA,ITALY. FU NHLBI NIH HHS [HL-36240] NR 45 TC 150 Z9 156 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 19151 EP 19156 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700068 PM 8034672 ER PT J AU UTANI, A NOMIZU, M TIMPL, R ROLLER, PP YAMADA, Y AF UTANI, A NOMIZU, M TIMPL, R ROLLER, PP YAMADA, Y TI LAMININ CHAIN ASSEMBLY - SPECIFIC SEQUENCES AT THE C-TERMINUS OF THE LONG ARM ARE REQUIRED FOR THE FORMATION OF SPECIFIC DOUBLE- AND TRIPLE-STRANDED COILED-COIL STRUCTURES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASEMENT-MEMBRANE PROTEINS; ALPHA-FIBROUS PROTEINS; MULTIDOMAIN PROTEIN; GLOBULAR DOMAIN; B2 CHAIN; A-CHAIN; CELLS; SUBUNITS; REPEATS; EXPRESSION AB The assembly of laminin chains into double- and triple-stranded structures was studied with recombinant proteins derived from the C-terminal alpha-helical region of the long arm of laminin. Both affinity assays and structural studies demonstrated chain-specific assembly of the B1, B2, and A chains, while associations between homotypic and homologous chains could not be observed. These results suggest that chain selection is controlled by the C-terminal region. Deletion mapping in the B1e and B2e chains identified two sites important for dimer and trimer formation. These two sites were separated by 23 amino acids in the B1e chain, whereas they were adjacent in the B2e chain. The Ae and Am chains contained only one site for trimerization. Site-directed mutagenesis revealed that charged amino acid residues within these sites were essential for association. These results suggest that distinct sites within the C-terminal alpha-helical region of the laminin long arm are critical for the chain-specific assembly of these macromolecules. C1 MAX PLANCK INST BIOCHEM, W-8033 MARTINSRIED, GERMANY. NCI, MED CHEM LAB, BETHESDA, MD 20892 USA. RP NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 34 TC 61 Z9 61 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 1994 VL 269 IS 29 BP 19167 EP 19175 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX327 UT WOS:A1994NX32700071 PM 8034675 ER PT J AU NEWMAN, AH ALLEN, AC IZENWASSER, S KATZ, JL AF NEWMAN, AH ALLEN, AC IZENWASSER, S KATZ, JL TI NOVEL 3-ALPHA-(DIPHENYLMETHOXY) TROPANE ANALOGS - POTENT DOPAMINE UPTAKE INHIBITORS WITHOUT COCAINE-LIKE BEHAVIORAL PROFILES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID BINDING; RECEPTOR; AFFINITY; SITES; TRANSPORTERS; ANTAGONISTS; SEROTONIN; LIGANDS RP NEWMAN, AH (reprint author), NIDA,PSYCHOBIOL SECT,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012 NR 32 TC 106 Z9 107 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 22 PY 1994 VL 37 IS 15 BP 2258 EP 2261 DI 10.1021/jm00041a002 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NZ411 UT WOS:A1994NZ41100002 PM 8057273 ER PT J AU CALDERON, SN IZENWASSER, S HELLER, B GUTKIND, JS MATTSON, MV SU, TP NEWMAN, AH AF CALDERON, SN IZENWASSER, S HELLER, B GUTKIND, JS MATTSON, MV SU, TP NEWMAN, AH TI NOVEL 1-PHENYLCYCLOALKANECARBOXYLIC ACID-DERIVATIVES ARE POTENT AND SELECTIVE SIGMA(1) LIGANDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR LIGANDS; ANTICONVULSANT AGENTS; BINDING-SITES; DEXTROMETHORPHAN; ANALOGS; DRUGS; IDENTIFICATION; PHENCYCLIDINE; AFFINITY AB Carbetapentane (1, 2-[2-(diethylamino)ethoxy]ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to sigma sites and is a potent antitussive, anticonvulsant, and spasmolytic agent. However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug. In an attempt to determine whether these psychoactivities can be attributed to interaction at sigma sites, a series of carbetapentane analogs were prepared. Phenyl ring substitution; contraction, expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated. All of these novel analogs were evaluated for binding to sigma(1) and sigma(2) sites, and comparison of binding at muscarinic m(1) and m(2) and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed. Ah of the compounds were selective for or over oz sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold). None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in >220-fold selectivity over muscarinic receptor binding. Therefore, several of these novel compounds are potent, sigma(1)-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents. These studies may reveal whether or sites play a role in the pharmacological actions of these drugs. C1 NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. NIDA,INTRAMURAL RES PROGRAM,PHARMACOL SECT,NEUROCHEM UNIT,BALTIMORE,MD 21224. NIDR,LCDO,MOLEC SIGNALING UNIT,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 35 TC 20 Z9 20 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 22 PY 1994 VL 37 IS 15 BP 2285 EP 2291 DI 10.1021/jm00041a006 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NZ411 UT WOS:A1994NZ41100006 PM 8057277 ER PT J AU TAL, M BENNETT, GJ AF TAL, M BENNETT, GJ TI NEUROPATHIC PAIN SENSATIONS ARE DIFFERENTIALLY SENSITIVE TO DEXTRORPHAN SO NEUROREPORT LA English DT Article DE ALLODYNIA; DEXTRORPHAN; HYPERALGESIA; NEUROPATHIC PAIN; NMDA ANTAGONIST ID PERIPHERAL NEUROPATHY; RAT; HYPERALGESIA; MODEL; NERVE AB RATS with an experimental painful peripheral neuropathy (the CCI model) display heat-hyperalgesia and mechano-allodynia. Previous work has shown that the heat-hyperalgesia is suppressed by dextrorphan (DEX) and other N-methyl-D-aspartate (NMDA) receptor antagonists. The present work shows that when tested in the same rats, a dose of DEX that is maximally effective against heat-hyperalgesia has no effect on mechano-allodynia. The results suggest that different kinds of abnormal pain sensations may be caused by different pathophysiologic mechanisms that may respond differently to drug therapy. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH DENT & MED SCH,DEPT ANAT,IL-91010 JERUSALEM,ISRAEL. NR 17 TC 85 Z9 85 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 21 PY 1994 VL 5 IS 12 BP 1438 EP 1440 DI 10.1097/00001756-199407000-00008 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PA497 UT WOS:A1994PA49700008 PM 7948833 ER PT J AU DAVIS, DL DINSE, GE HOEL, DG AF DAVIS, DL DINSE, GE HOEL, DG TI DECREASED CARDIOVASCULAR-DISEASE AND INCREASING CANCER - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID BREAST-CANCER C1 NIEHS,RES TRIANGLE PK,NC 27709. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP DAVIS, DL (reprint author), US DEPT HLTH & HUMAN SERV,WASHINGTON,DC, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 20 PY 1994 VL 272 IS 3 BP 199 EP 200 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NW185 UT WOS:A1994NW18500009 ER PT J AU SCHATZKIN, A FREEDMAN, LS DAWSEY, SM LANZA, E AF SCHATZKIN, A FREEDMAN, LS DAWSEY, SM LANZA, E TI INTERPRETING PRECURSOR STUDIES - WHAT POLYP TRIALS TELL US ABOUT LARGE-BOWEL CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COLORECTAL ADENOMATOUS POLYPS; CELL-PROLIFERATION; RISK; EPIDEMIOLOGY; RECTUM; COLON RP SCHATZKIN, A (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,EPN,RM 211,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 21 TC 37 Z9 38 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 JUL 20 PY 1994 VL 86 IS 14 BP 1053 EP 1057 DI 10.1093/jnci/86.14.1053 PG 5 WC Oncology SC Oncology GA NW605 UT WOS:A1994NW60500008 PM 7802771 ER PT J AU POTTER, M MORRISON, S WIENER, F ZHANG, XKK MILLER, FW AF POTTER, M MORRISON, S WIENER, F ZHANG, XKK MILLER, FW TI INDUCTION OF PLASMACYTOMAS WITH SILICONE GEL IN GENETICALLY SUSCEPTIBLE STRAINS OF MICE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PRISTANE-INDUCED ARTHRITIS; BREAST IMPLANTS; TRANSLOCATIONS; GROWTH; WOMEN; AUTOANTIBODIES; INTERLEUKIN-6; REQUIREMENT; PROTEINS; MYELOMA AB Background: Plasmacytomas can be induced in high frequency in susceptible strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10,14-tetramethglpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcription. Purpose: Because silicone gels are in widespread medical use and share many of the characteristics of other materials known to be inducers of plasmacytomas, we wished to determine their capacity to induce plasmacytomas in mice. Methods: In a series of parallel experiments, corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraperitoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB/cAnPt.DB A/2-Idhl-Pep3 mice, as well as into plasmacytoma-resistant C57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were examined at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for; peritoneal-plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohistechemical techniques. Metaphase chromosome spreads were made from ascitic plasmacytomas without Colcemid treatment, and metaphase plates were G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsied 125-400 days after the injection of test material. Gas chromatography and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. Results: The silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idhl-Pep3 mice. Neither corn oil used as a control nor 1000-centistoke or 12500-centistoke dimethylpolysiloxane induced plasmacytomas in these mice. The plasmacytomas were transplantable in syngeneic hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas showed that 30 had t(12;15) translocations, eight had t(6;15) translocations, and three had no translocations. Conclusions: The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials. C1 KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM,SWEDEN. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD. RP POTTER, M (reprint author), NCI,DIV CANC BIOL DIAG & CTR,BLDG 37,RM 2B04,BETHESDA,MD 20892, USA. NR 40 TC 89 Z9 89 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 20 PY 1994 VL 86 IS 14 BP 1058 EP 1065 DI 10.1093/jnci/86.14.1058 PG 8 WC Oncology SC Oncology GA NW605 UT WOS:A1994NW60500009 PM 8021954 ER PT J AU DAVIS, CD GHOSHAL, A SCHUT, HAJ SNYDERWINE, EG AF DAVIS, CD GHOSHAL, A SCHUT, HAJ SNYDERWINE, EG TI METABOLISM OF THE FOOD-DERIVED CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B] PYRIDINE BY LACTATING FISCHER-344 RATS AND THEIR NURSING PUPS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; HETEROCYCLIC AMINES; LIVER-MICROSOMES; BREAST-MILK; DNA-ADDUCTS; PHIP; ACTIVATION; MEIQX; IQ; MONKEYS AB Background: An important class of dietary mutagens and carcinogens are the heterocyclic arylamine compounds that have been identified in a variety of cooked, protein-containing foods. Among these heterocyclic amines, 2-amino-l-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) is potentially the most important carcinogen for human cancer risk. We have recently observed that PhIP-derived radioactivity is excreted into the breast milk of lactating rats administered [H-3]PhIP. Purpose: To better assess the significance of breast milk as a route of exposure of the newborn to dietary heterocyclic amines, we examined the metabolites of PhIP in breast milk and in urine of nursing pups. Methods: Lactating Fischer 344 rats with 5-day-old pups were given a single oral dose of 10 mg/kg of[H-3]PhIP. We collected milk from the dams and urine from the pups and then analyzed the samples for metabolites of PhIP, using high-pressure liquid chromatography (HPLC). PhlP-DNA adduct levels in the tissues of the pups were determined by P-32-postlabeling analysis. Results: Three radioactive peaks were observed by HPLC separation of milk samples: an unidentified early eluting peak, 4 '-hydroxy-PhIP, and PhIP. Four metabolites and the parent compound were found in urine of the pups nursed by dams given radiolabeled PhIP: PhIP4 '-O-glucuronide, PhIP-4 '-sulfate, 4 '-hydroxy-PhIP, and N-2-hydroxy-PhIP-N-3-glucuronide. 4 '-Hydroxy-PhIP and its conjugates contributed approximately 60% of the radioactivity found in the urine. By P-32-postlabeling analysis, PhIP-DNA adducts were detected in spleen, lung, heart, kidney, liver, and stomach of pups at mean levels ranging from 0.06 to 0.55 adducts/l0(7) nucleotides. Conclusions: The large percentage of 4 '-hydroxy-PhIP and its conjugates in the urine indicates that 5-day-old pups detoxify PhIP and further metabolize 4 '-hydroxy-PhIP obtained from the breast milk. The presence of the glucuronide conjugate of N-hydroxy-PhIP in the urine of pups and the lack of detectible conjugate or N-hydroxylamine itself in breast milk suggest that PhIP from breast milk undergoes metabolic activation via N-hydroxytation in 5-day-old rat pups. This conclusion was further supported by the observation that hepatic S9 fractions from the pups activated PhIP to a mutagen in the Ames Salmonella mutagenicity assay and by the presence of PhIP-DNA adducts in the tissues of the pups. Implications: The findings reported here may have carcinogenic and toxicologic implications for the offspring of women who breast-feed and consume a diet rich in cooked meat. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. RP DAVIS, CD (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 30 TC 20 Z9 20 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 20 PY 1994 VL 86 IS 14 BP 1065 EP 1070 DI 10.1093/jnci/86.14.1065 PG 6 WC Oncology SC Oncology GA NW605 UT WOS:A1994NW60500010 PM 8021955 ER PT J AU KUNKEL, TA PATEL, SS JOHNSON, KA AF KUNKEL, TA PATEL, SS JOHNSON, KA TI ERROR-PRONE REPLICATION OF REPEATED DNA-SEQUENCES BY T7 DNA-POLYMERASE IN THE ABSENCE OF ITS PROCESSIVITY SUBUNIT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FIDELITY; STRAND SLIPPAGE; DNA REPLICATION; ACCESSORY PROTEINS ID DEOXYRIBONUCLEIC-ACID POLYMERASE; ESCHERICHIA-COLI THIOREDOXIN; HIV-1 REVERSE-TRANSCRIPTASE; GENE-5 PROTEIN; MUTATIONAL SPECIFICITY; EXONUCLEASE ACTIVITIES; INVITRO; BACTERIOPHAGE-T7; MECHANISM; FIDELITY AB We have examined the effect of thioredoxin, an accessory protein that confers high processivity to bacteriophage T7 DNA polymerase, on the fidelity of DNA synthesis. In the presence of thioredoxin, exonuclease-proficient T7 DNA polymerase is highly accurate. In fidelity assays that score errors that revert M13mp2 lacZ alpha-complementation mutants, error rates are less than or equal to 2.2 x 10(-6) for base substitution and less than or equal to 3.7 x 10(-7) and less than or equal to 4.5 x 10(-7) for frameshifts that revert mutations in the +1 and -1 reading frames, respectively. Rates are more than 10-fold higher during synthesis by polymerase.thioredoxin complex lacking 3' --> 5' exonuclease activity, demonstrating that frameshift as well as substitution errors are subject to proofreading. The contribution of thioredoxin to accuracy has been examined by comparing the fidelity of the exonuclease-deficient polymerase in the presence or absence of the accessory protein. Thioredoxin either enhances or reduces fidelity, depending on the type of error considered. In the absence of thioredoxin, T7 DNA polymerase is 3-fold more accurate for base substitutions and greater than or equal to 27-fold and 9-fold more accurate, respectively, for 1- and 2-nt deletion errors at nonreiterated nucleotide sequences. Higher fidelity for all three errors may reflect the inability of the polymerase to continue synthesis from the premutational intermediates in the absence of the accessory protein. In marked contrast, the rate for frameshift errors wherein one or more nucleotides has been added to a repeated DNA sequence increases 46-fold when thioredoxin is absent from the polymerization reaction. The error rate increases as the length of the repeated sequence increases, consistent with a model where strand slippage creates misaligned template-primers. Thus, replicative expansion of repetitive sequences occurs in the absence of a replication accessory protein. C1 PENN STATE UNIV,DEPT MOLEC & CELL BIOL,UNIV PK,PA 16802. RP KUNKEL, TA (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 88 Z9 88 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 6830 EP 6834 DI 10.1073/pnas.91.15.6830 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800018 PM 8041704 ER PT J AU KREITMAN, RJ PURI, RK PASTAN, I AF KREITMAN, RJ PURI, RK PASTAN, I TI A CIRCULARLY PERMUTED RECOMBINANT INTERLEUKIN-4 TOXIN WITH INCREASED ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOTOXIN; GROWTH FACTOR; PSEUDOMONAS TOXIN; RECOMBINANT DNA; CYTOKINE ID 3-DIMENSIONAL SOLUTION STRUCTURE; MAGNETIC-RESONANCE SPECTROSCOPY; COLONY-STIMULATING FACTOR; PSEUDOMONAS EXOTOXIN; FUSION PROTEIN; GENETIC CONSTRUCTION; DIPHTHERIA-TOXIN; RECEPTOR-BINDING; ESCHERICHIA-COLI; GROWTH-FACTORS AB Fusion of ligands such as growth factors to other proteins often dramatically reduces the affinity of the ligand for its receptor. With recombinant DNA techniques, the attachment point between the two proteins has until now been restricted to either the amino or the carboxyl terminus of the ligand. However, binding may be greatly compromised if both ends are close to the site at which the ligand binds to its receptor. To construct a single-chain growth factor fusion protein with the connection at a new site on the growth factor, we constructed a DNA fragment encoding circularly permuted interleukin 4 (IL4), termed IL4(38-37). This was accomplished by placing a start codon before position 38, connecting codons 1 and 129 with a sequence encoding a; peptide linker, and placing a stop codon after codon 37 of IL4. IL4(38-37) was fused via its new carboxyl terminus, Lys(37), to a truncated form of Pseudomonas exotoxin. The purified circularly permuted IL4-toxin bound to the IL4 receptor with 10-fold higher affinity than an IL4-toxin in which the toxin was fused to the carboxyl terminus of IL4. Circular permuteins of growth factors can improve the effectiveness of recombinant fusion proteins, because the junction can be moved to a site on the growth factor which allows it to bind with higher affinity. C1 NCI,DIAGNOSIS & CTRS,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NR 41 TC 94 Z9 97 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 JUL 19 PY 1994 VL 91 IS 15 BP 6889 EP 6893 DI 10.1073/pnas.91.15.6889 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800030 PM 8041715 ER PT J AU BENVENISTE, P TAKAHAMA, Y WIEST, DL NAKAYAMA, T SHARROW, SO SINGER, A AF BENVENISTE, P TAKAHAMA, Y WIEST, DL NAKAYAMA, T SHARROW, SO SINGER, A TI ENGAGEMENT OF THE EXTERNAL DOMAINS OF CD45 TYROSINE PHOSPHATASE CAN REGULATE THE DIFFERENTIATION OF IMMATURE CD4+CD8+ THYMOCYTES INTO MATURE T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE KINASE; POSITIVE SELECTION; THYMUS ID RECEPTOR EXPRESSION; CD4+CD8+ THYMOCYTES; PROTEIN-KINASE; ANTIGEN RECEPTOR; PHOSPHORYLATION; INHIBITION; P56(LCK); EVENTS; P56LCK; MICE AB Immature precursor cells are induced in the thymus to express clonotypic T-cell antigen receptors (TCRs) and to differentiate into mature T cells. Perhaps the least understood event which occurs during intrathymic development is the positive selection of immature CD4(+)CD8(+) thymocytes for differentiation into mature CD4(+) and CD8(+) T cells based on the TCR specificity individual thymocytes express. TCR expression by CD4(+)CD8(+) thymocytes is quantitatively regulated by CD4-mediated activation of p56(lck) protein-tyrosine kinase whose activity can in turn be regulated by the membrane-bound protein-tyrosine-phosphatase CD45. Here we show that antibody engagement of CD45 external domains enhances Lck tyrosine kinase activity in CD4(+)CD8(+) thymocytes, inhibits TCR expression, and inhibits differentiation of immature CD4(+)CD8(+) thymocytes into mature T cells. Thus, engagement of the external domains of CD45 tyrosine phosphatase can regulate the ability of immature CD4(+)CD8(+) thymocytes to undergo positive selection, suggesting an important regulatory role for intrathymic ligands that are capable of engaging CD45 within the thymus. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RI Nakayama, Toshinori/E-1067-2017; OI Wiest, David/0000-0002-0792-3188 NR 31 TC 13 Z9 13 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 JUL 19 PY 1994 VL 91 IS 15 BP 6933 EP 6937 DI 10.1073/pnas.91.15.6933 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800039 PM 8041724 ER PT J AU ASOH, S LEEKWON, W MOURADIAN, MM NIRENBERG, M AF ASOH, S LEEKWON, W MOURADIAN, MM NIRENBERG, M TI SELECTION OF DNA CLONES WITH ENHANCER SEQUENCES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA REPLICATION; GENE TRANSCRIPTION; POLYOMA DNA ID POLYOMA-VIRUS GENOME; EARLY GENE-EXPRESSION; LARGE T-ANTIGEN; CHLORAMPHENICOL ACETYLTRANSFERASE; ACTIVATOR ELEMENTS; SIMIAN VIRUS-40; CELLULAR DNA; REPLICATION; REGION; CELLS AB A method is described for selection of DNA clones that contain enhancer sequences that activate gene expression. An Escherichia coli-rodent cell shuttle vector, pPyE0, was used that contains polyoma viral DNA without the polyoma enhancer region. Replication of pPyE0 DNA in mouse cells is markedly reduced due to deletion of the polyoma enhancer region. insertion of mouse genomic DNA fragments that contain putative enhancer sequences into pPyE0 adjacent to the polyoma origin of replication restored, to varying extents, the ability of the recombinant plasmid DNA to replicate in mouse cells. Recombinant plasmids that replicate well in mouse cells, therefore, are amplified selectively. Transfection of mouse neuroblastoma or fibroblast cells that constitutively synthesize polyoma large tumor antigen with a library of mouse genomic DNA fragments inserted in pPyE0 yielded many recombinant plasmids. DNA inserts from each of the 16 clones that were examined stimulated the expression of an enhancerless chloramphenicol acetyltransferase reporter gene. The DNA inserts from 4 clones that were studied resulted in 4- to 13-fold increases in chloramphenicol acetyltransferase mRNA in transfected mouse cells. Nucleotide sequence analysis led to the identification of 5 genomic DNA clones that were obtained by selection. All of the homologies found were to regions of DNA that are thought to be involved in the regulation of gene expression. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 30 TC 6 Z9 6 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 6982 EP 6986 DI 10.1073/pnas.91.15.6982 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800049 PM 8041732 ER PT J AU CHAE, HZ ROBISON, K POOLE, LB CHURCH, G STORZ, G RHEE, SG AF CHAE, HZ ROBISON, K POOLE, LB CHURCH, G STORZ, G RHEE, SG TI CLONING AND SEQUENCING OF THIOL-SPECIFIC ANTIOXIDANT FROM MAMMALIAN BRAIN - ALKYL HYDROPEROXIDE REDUCTASE AND THIOL-SPECIFIC ANTIOXIDANT DEFINE A LARGE FAMILY OF ANTIOXIDANT ENZYMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FLAVOPROTEIN DISULFIDE OXIDOREDUCTASES; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SACCHAROMYCES-CEREVISIAE; SPONTANEOUS MUTAGENESIS; THIOREDOXIN REDUCTASE; NADH DEHYDROGENASE; MOLECULAR ANALYSIS; OXIDATIVE DAMAGE; GENE AB A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA. The cDNA clone encoded an open reading frame capable of encoding a 198-residue polypeptide. The rat and yeast TSA proteins Show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of >25 different proteins present in organisms from all kingdoms. The similarity among the family members extends over the entire sequence and ranges between 23% and 98% identity. A majority of the members of the AhpC/TSA family contain two conserved cysteines. At least eight of the genes encoding AhpC/TSA-like polypeptides are found in proximity to genes encoding other oxidoreductase activities, and the expression of several Of the homologs has been correlated with pathogenicity. We suggest that the AhpC/TSA family represents a widely distributed class of antioxidant enzymes. We also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by thioredoxin reductase, has expanded to include six additional members, C1 NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT BIOCHEM, WINSTON SALEM, NC 27157 USA. OI Storz, Gisela/0000-0001-6698-1241 FU NIGMS NIH HHS [R01 GM050389] NR 38 TC 600 Z9 633 U1 2 U2 13 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 JUL 19 PY 1994 VL 91 IS 15 BP 7017 EP 7021 DI 10.1073/pnas.91.15.7017 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800056 PM 8041738 ER PT J AU CHAE, HZ UHM, TB RHEE, SG AF CHAE, HZ UHM, TB RHEE, SG TI DIMERIZATION OF THIOL-SPECIFIC ANTIOXIDANT AND THE ESSENTIAL ROLE OF CYSTEINE-47 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; CLONING AB Thiol-specific antioxidant (TSA) from yeast contains cysteine residues at amino acid positions 47 and 170 but is not associated with obvious redox cofactors. These two cysteines are highly conserved in a family of proteins that exhibit sequence identity of 23-98% with TSA. The roles of Cys-47 and Cys-170 in yeast TSA were investigated by replacing them individually with serine and expressing the mutant TSA proteins (RC47S and RC170S, respectively), as well as wild-type TSA (RWT), in Escherichia coli. Wild-type TSA purified from yeast (YWT) and RWT were both shown to exist predominantly as dimers, whereas RC47S and RC170S existed mainly as monomers under a denaturing condition. This observation suggests that the dimerization of YWT and RWT requires disulfide linkage of Cys-47 and Cys-170. The presence of the Cys-47-Cys-170 linkage in YWT was directly shown by isolation of dimeric tryptic peptides, one monomer of which contained Cys-47 and the other contained Cys-170. A small percentage of YWT, RWT, RC47S, and RC170S molecules formed diners linked by Cys-47-Cys-47 or Cys-170-Cys-170 disulfide bonds. The antioxidant activity of the various TSA proteins was evaluated from their ability to protect glutamine synthetase against the dithiothreitol/Fe3+/O-2 oxidation system. YWT, RWT, and RC170S were equally protective, whereas RC47S was completely ineffective. Thus, Cys-47, but not Cys-170, constitutes the site of oxidation by putative substrate. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 8 TC 245 Z9 252 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7022 EP 7026 DI 10.1073/pnas.91.15.7022 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800057 PM 8041739 ER PT J AU HURSTING, SD PERKINS, SN PHANG, JM AF HURSTING, SD PERKINS, SN PHANG, JM TI CALORIE RESTRICTION DELAYS SPONTANEOUS TUMORIGENESIS IN P53-KNOCKOUT TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR SUPPRESSOR GENE; WILD-TYPE P53; TISSUES AB Transgenic mice with both alleles of the p53 tumor suppressor gene (frequently mutated in human tumors) knocked out by gene targeting provide a potentially useful tumorigenesis model because these mice rapidly develop spontaneous tumors. To determine whether tumorigenesis in p53-knockout mice is sensitive to experimental manipulation, tumor development in response to calorie restriction (CR; a potent inhibitor of rodent tumors) was evaluated. Tumor development was monitored for 48 weeks in male nullizygous p53-knockout and wild-type littermate mice (28-30 per treatment group) fed ad libitum (AL) or restricted to 60% of AL carbohydrate calorie intake. CR:p53-knockout mice (median survival = 25 weeks) experienced a delay in tumor onset and subsequent mortality (P = 0.0002) relative to AL:p53-knockout mice (median survival = 16 weeks). Tumor development and mortality in wildtype littermates on either diet treatment were <4% through 48 weeks. Cell cycle analyses were performed on splenocytes from p53-knockout mice and wild-type littermates after 4 weeks of AL feeding or CR (5 per group). The percentage of splenocytes in S phase of the cell cycle was 3-fold higher for p53-knockout mice than wild-type mice (P < 0.001), and CR reduced the percentage of S-phase splenocytes in both p53-knockout and wild-type mice (P = 0.012). These data demonstrate that tumor development in p53-knockout mite genetically predisposed to tumors can be delayed by CR (possibly via cell cycle modulation) and suggest that these mice provide a very useful model of spontaneous tumorigenesis. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC PREVENT & CONTROL,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21702. NR 21 TC 122 Z9 125 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7036 EP 7040 DI 10.1073/pnas.91.15.7036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800060 PM 8041741 ER PT J AU ZHOU, BK KOBAYASHI, T DONATIEN, PD BENNETT, DC HEARING, VJ ORLOW, SJ AF ZHOU, BK KOBAYASHI, T DONATIEN, PD BENNETT, DC HEARING, VJ ORLOW, SJ TI IDENTIFICATION OF A MELANOSOMAL MATRIX PROTEIN ENCODED BY THE MURINE SI (SILVER) LOCUS USING ORGANELLE SCANNING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GRAYING; TYROSINASE; COAT COLOR; MELANOMA; PROGRAMMED CELL DEATH ID INTEGRAL MEMBRANE-PROTEINS; DOPACHROME TAUTOMERASE; MOUSE MELANOCYTES; TYROSINASE; GENE; CDNA; PMEL-17 AB To identify a broad spectrum of melanosomal proteins, antisera were raised in rabbits against melanosomal protein fractions separated on the basis of their solubility in the nonionic detergent Triton X-114. Antisera against the different fractions each recognized a distinct set of bands when used for inmunoblotting analysis with extracts of melanocytes cultured from wild-type black mice. Immunoblotting with antisera to whole melanosomes or to Triton X-114-soluble melanosomal proteins that segregated with the detergent phase gave identical patterns with protein extracts from melanocytes from wild-type mice and from mice homozygous for the si (silver) coat color mutation. By contrast, an antiserum against Triton X-114 soluble melanosomal proteins that segregated in the aqueous phase recognized an 85-kDa protein that was present in extracts from wild-type melanocytes but was absent from si melanocytes. This suggested that the protein was encoded at the si (silver) locus. This was confirmed by employing an antiserum directed against the carboxyl terminus of the predicted murine silver protein sequence. The detergent solubility, biochemical characteristics, and immunologic properties of the 85-kDa protein and of the authentic si gene product were identical. Further analysis demonstrated that this protein corresponds to a melanosomal matrix glycoprotein that we recently described. Our results suggest that employing polyclonal antisera to fractionated organelles such as melanosomes, to screen tissues from mutant mice, a technique that we call ''organelle scanning'', can serve as a powerful means of identifying new organellar proteins and their respective genes. C1 NYU,SCH MED,RONALD O PERELMAN DEPT DERM,NEW YORK,NY 10016. NYU,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. ST GEORGE HOSP,SCH MED,DEPT ANAT,LONDON,ENGLAND. RI Bennett, Dorothy/C-2418-2008 OI Bennett, Dorothy/0000-0002-3639-7527 FU NIAMS NIH HHS [AR41880] NR 25 TC 49 Z9 50 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7076 EP 7080 DI 10.1073/pnas.91.15.7076 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800068 PM 8041749 ER PT J AU ADAMS, DH HARVATH, L BOTTARO, DP INTERRANTE, R CATALANO, G TANAKA, Y STRAIN, A HUBSCHER, SG SHAW, S AF ADAMS, DH HARVATH, L BOTTARO, DP INTERRANTE, R CATALANO, G TANAKA, Y STRAIN, A HUBSCHER, SG SHAW, S TI HEPATOCYTE GROWTH-FACTOR AND MACROPHAGE INFLAMMATORY PROTEIN 1-BETA - STRUCTURALLY DISTINCT CYTOKINES THAT INDUCE RAPID CYTOSKELETAL CHANGES AND SUBSET-PREFERENTIAL MIGRATION IN T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SCATTER FACTOR; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; FACTOR-RECEPTOR; RAT-TISSUES; EXPRESSION; LYMPHOCYTES; MOTILITY; ACTIN AB T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. ''Triggering'' is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion and migration of human T-cell subsets and can be detected immunohistochemically on inflamed endothelium. HGF preferentially induces responses from T cells of memory phenotype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 beta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular matrix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approach those required to contribute to physiologic triggering. HGF is a member of a structural family distinct from the chemokines, whose only known receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosphorylation on T cells apparently via a distinct receptor, since no c-Met is detectable by surface staining, PCR, or anti-phosphotyrosine immunoprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant to selective T-cell recruitment. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. UNIV ROME,DEPT HEMATOL,ROME,ITALY. UNIV BIRMINGHAM,DEPT BIOCHEM,BIRMINGHAM B15 2TT,ENGLAND. UNIV BIRMINGHAM,DEPT PATHOL,BIRMINGHAM B15 2TT,ENGLAND. RP ADAMS, DH (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010; Adams, David/C-9092-2009 OI Bottaro, Donald/0000-0002-5057-5334; NR 43 TC 107 Z9 107 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 JUL 19 PY 1994 VL 91 IS 15 BP 7144 EP 7148 DI 10.1073/pnas.91.15.7144 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800082 PM 8041760 ER PT J AU BRETZ, JD WILLIAMS, SC BAER, M JOHNSON, PF SCHWARTZ, RC AF BRETZ, JD WILLIAMS, SC BAER, M JOHNSON, PF SCHWARTZ, RC TI C/EBP-RELATED PROTEIN-2 CONFERS LIPOPOLYSACCHARIDE-INDUCIBLE EXPRESSION OF INTERLEUKIN-6 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 TO A LYMPHOBLASTIC CELL-LINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION FACTOR; CYTOKINE; INFLAMMATION ID COLONY-STIMULATING FACTOR; NF-KAPPA-B; SYNERGISTICALLY ACTIVATE TRANSCRIPTION; MURINE PERITONEAL-MACROPHAGES; MESSENGER-RNA; GENE-EXPRESSION; LEUCINE ZIPPER; FACTORS INTERACT; FAMILY MEMBERS; NUCLEAR FACTOR AB C/EBP-related proteins 2 and 3 (CRP2 and CRP3) are differentially expressed by P388 lymphoblasts and their derivative P388D1(IL1) macrophages. We have ectopically expressed CRP2, the predominant CRP in macrophages, in P388 lymphoblasts. The expression of CRP2 is sufficient to confer the lipopolysaccharide (LPS)-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to lymphoblasts, which normally do not display LPS induction of inflammatory cytokines. Consistent with these findings, the expression of CRP2 antisense RNA blocks the LPS induction of IL-6 expression in P388D1(IL1) macrophages. This work clearly establishes the essential role of CRP2 in the induction of cytokine genes by LPS. Additionally, these data add MCP-1 to the list of cytokines showing an involvement of CRP2 in their expression. C1 MICHIGAN STATE UNIV,DEPT MICROBIOL,E LANSING,MI 48824. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NCI NIH HHS [CA45360, N01-CO-74101] NR 46 TC 73 Z9 73 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 JUL 19 PY 1994 VL 91 IS 15 BP 7306 EP 7310 DI 10.1073/pnas.91.15.7306 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800115 PM 8041785 ER PT J AU PHILPOTT, CC KLAUSNER, RD ROUAULT, TA AF PHILPOTT, CC KLAUSNER, RD ROUAULT, TA TI THE BIFUNCTIONAL IRON-RESPONSIVE ELEMENT-BINDING PROTEIN CYTOSOLIC ACONITASE - THE ROLE OF ACTIVE-SITE RESIDUES IN LIGAND-BINDING AND REGULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MUTAGENESIS; RNA BINDING ID FE-S CLUSTER; RNA-BINDING; CYTOSOLIC ACONITASE; SULFUR CLUSTER; MESSENGER-RNA; PROTEIN; RECOGNITION; CRYSTAL; GENE AB The iron-responsive element binding protein/cytosolic aconitase functions as either an RNA binding protein that regulates the uptake, sequestration, and utilization of iron or an enzyme that interconverts citrate and isocitrate. These mutually exclusive functions are regulated by changes in cellular iron levels. By site-directed mutagenesis we show that (i) ligation of a [4Fe-4S] cluster is necessary to inactivate RNA binding and activate enzyme function in vivo, (ii) three of four arginine residues of the aconitase active site participate in RNA binding, and (iii) aconitase activity is not required for iron-mediated regulation of RNA binding. RP PHILPOTT, CC (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 92 Z9 93 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7321 EP 7325 DI 10.1073/pnas.91.15.7321 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800118 PM 8041788 ER PT J AU KIM, IY STADTMAN, TC AF KIM, IY STADTMAN, TC TI EFFECTS OF MONOVALENT CATIONS AND DIVALENT METAL-IONS ON ESCHERICHIA-COLI SELENOPHOSPHATE SYNTHETASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MANGANESE; ATP; ZINC INHIBITION ID TRANSFER-RNA-SYNTHETASE; SELD GENE-PRODUCT; SELENIUM METABOLISM; BINDING SITE; 5-METHYLAMINOMETHYL-2-SELENOURIDINE; NUCLEOSIDE; MUTANT; DONOR AB A labile selenium donor compound, selenophosphate, is formed from selenide and ATP by selenophosphate synthetase. A divalent metal ion, Mg2+, and a monovalent cation, K+, NH4+, or Rb+, are required for selenophosphate synthetase activity [Veres, Z., Kim, I. Y., Scholz, T. D. and Stadtman, T. C. (1994) J. Biol. Chem. 269, 10597-10603]. Na+ and Li+ are ineffective as activators and in the presence of K+ are inhibitory. Mn-ATP, although not able to replace Mg-ATP for catalytic activity, binds to the enzyme provided an active monovalent cation is present. No Mn-ATP is bound when K+ is replaced with Na+. The requirement for K+, both for Mn-ATP binding and for catalytic activity of the synthetase, indicates a specific monovalent cation-induced conformational state of the enzyme. Previously we reported that activity of the enzyme is markedly inhibited by micromolar levels of Zn2+ in the presence of millimolar levels of Mg2+ [Kim, I. Y., Veres, Z. and Stadtman, T. C. (1993) J. Biol. Chem. 268, 27020-27025]. Binding of Mn-ATP also is decreased upon addition of Zn2+, indicating that the inhibitory effect of Zn2+ is exerted at the substrate-binding step of the overall selenophosphate synthetase reaction. When a cysteine residue at position 17 or 19 is replaced with serine, Mn-ATP binding to these mutant enzymes is unaffected by Zn2+ addition. Direct involvement of these cysteine residues in the zinc binding site was shown by use of (ZnCl2)-Zn-65. Radioactive Zn2+ bound to wild-type enzyme and was retained after gel filtration, but under the same conditions the catalytically inactive Cys-17 mutant protein and the catalytically active Cys-19 mutant enzyme were unlabeled. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 20 TC 15 Z9 17 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 JUL 19 PY 1994 VL 91 IS 15 BP 7326 EP 7329 DI 10.1073/pnas.91.15.7326 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800119 PM 8041789 ER PT J AU LIN, AMY SCHAAD, NC SCHULZ, PE COON, SL KLEIN, DC AF LIN, AMY SCHAAD, NC SCHULZ, PE COON, SL KLEIN, DC TI PINEAL NITRIC-OXIDE SYNTHASE - CHARACTERISTICS, ADRENERGIC REGULATION AND FUNCTION SO BRAIN RESEARCH LA English DT Article DE NITRIC OXIDE SYNTHASE; NITRIC OXIDE; CAMP ID N-ACETYLTRANSFERASE ACTIVITY; PROTEIN-KINASE-C; CYCLIC-GMP FORMATION; RAT PINEALOCYTES; GUANOSINE 3',5'-MONOPHOSPHATE; GUANYLATE-CYCLASE; CGMP ACCUMULATION; AMP RESPONSE; STIMULATION; CALMODULIN AB Available studies indicate that the adrenergic stimulation of pineal cyclic GMP production involves stimulation of guanylyl cyclase activity by nitric oxide (NO) derived from arginine. This line of investigation was extended in the present study. Using a highly sensitive microassay, it was found that pineal NO synthase activity is present at levels similar to 30% of those in the cerebellum, that approximately 95% of enzyme activity is cytoplasmic, that the enzyme is Ca2+/calmodulin-dependent and that enzyme activity is inhibited by the arginine analog N-G-nitro-L-arginine methyl ester (L-NAME). Norepinephrine treatment of intact glands in culture increased [H-3]citrulline formation from [H-3]arginine. This treatment also increased the formation of an NO-like compound, indicating that NO synthase activity in the intact gland is elevated by adrenergic stimulation. Studies on the effects of inhibition of NO synthase activity indicated that treatments known to inhibit NO synthase activity and the adrenergic stimulation of cyclic GMP accumulation did not inhibit adrenergic stimulation of pineal cyclic AMP, N-acetyltransferase activity or melatonin production. These observations support the hypothesis that NE stimulation of pineal cyclic GMP accumulation involves stimulation of a Ca2+/calmodulin-sensitive form of NO synthase, resulting in enhanced accumulation of NO; and, that although NO appears to play a role in the adrenergic stimulation of pineal cyclic GMP accumulation, it does not appear to play a critical role in the adrenergic stimulation of cyclic AMP, N-acetyltransferase activity or melatonin production. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. INST UNIV PSYCHIAT,DIV PSYCHOPHARMACOL CLIN,CH-1225 CHENE BOURG,SWITZERLAND. NR 46 TC 43 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 18 PY 1994 VL 651 IS 1-2 BP 160 EP 168 DI 10.1016/0006-8993(94)90693-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NX150 UT WOS:A1994NX15000020 PM 7522930 ER PT J AU ROSEN, JB WEISS, SRB POST, RM AF ROSEN, JB WEISS, SRB POST, RM TI CONTINGENT TOLERANCE TO CARBAMAZEPINE - ALTERATIONS IN TRH MESSENGER-RNA AND TRH RECEPTOR-BINDING IN LIMBIC STRUCTURES SO BRAIN RESEARCH LA English DT Article DE KINDLING; THYROTROPIN-RELEASING HORMONE; CARBAMAZEPINE; TOLERANCE; HIPPOCAMPUS; ENTORHINAL CORTEX; PYRIFORM CORTEX; PERIRHINAL CORTEX; MESSENGER-RNA; IN SITU HYBRIDIZATION ID AMYGDALA-KINDLED SEIZURES; THYROTROPIN-RELEASING-HORMONE; MESSENGER-RNA; C-FOS; RATS; EXPRESSION; BRAIN; VALPROATE; DIAZEPAM; PROTEIN AB Tolerance to carbamazepine's anticonvuslant effects on amygdala kindled seizures occurs contingently, that is, only when carbamazepine is given prior to, but not after the seizure occurs. Biological correlates of contingent tolerance were examined using in situ hybridization and receptor binding techniques for thyrotropin-releasing hormone (TRH) mRNA and TRH receptor binding. Rats were fully kindled and given daily injections of carbamazepine (15 mg/kg, i.p.) either 15 min before (CBZ-before) or after (CBZ-after) amygdala stimulation until the CBZ-before rats became tolerant. Kindled rats were matched so that the two groups had an equal number of seizures and doses of CBZ. Three other groups were also used for comparison: kindled rats that received vehicle injections, and sham-kindled animals treated with either vehicle or CBZ. Rats were sacrificed 4 h after the last seizure or sham stimulation. Both sham-kindled rat groups had barely detectable levels of TRH mRNA. In the CBZ-after (non-tolerant) and vehicle-kindled rats, TRH mRNA levels were increased in the dentate gyrus, pyriform, entorhinal, and perirhinal cortices. In contrast to the other kindled animals, the CBZ-before rats (tolerant) had dramatically diminished TRH mRNA levels bilaterally in the dentate gyrus and pyriform cortex, and ipsilateral to the stimulation in the entorhinal cortex. Decreases in TRH receptor binding were demonstrated autoradiographically in the dentate gyrus and perirhinal cortex in all of the kindled groups with no differences between tolerant and non-tolerant rats. The reported TRH mRNA alterations are, thus, specifically associated with the development of contingent tolerance and are not attributable to either the occurence of seizures or repeated drug exposure alone. The role of TRH in carbamazepine's anticonvulsant effects and the functional consequences of the failure of CBZ-tolerant animals to show seizure-induced increases in TRH mRNA warrants further investigation. RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 39 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 18 PY 1994 VL 651 IS 1-2 BP 252 EP 260 DI 10.1016/0006-8993(94)90704-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NX150 UT WOS:A1994NX15000031 PM 7922572 ER PT J AU FUKAMAUCHI, F CHUANG, DM AF FUKAMAUCHI, F CHUANG, DM TI ENDOTHELIN-1 INCREASES THE LEVELS OF MESSENGER-RNA AND PROTEIN OF MUSCARINIC ACETYLCHOLINE-RECEPTORS AND C-FOS MESSENGER-RNA IN CEREBELLAR GRANULE CELLS SO FEBS LETTERS LA English DT Article DE ENDOTHELIN-1; MUSCARINIC ACETYLCHOLINE RECEPTOR MESSENGER-RNA; C-FOS MESSENGER-RNA; NORTHERN BLOT HYBRIDIZATION; IMMUNOPRECIPITATION; CEREBELLAR GRANULE ID INDUCED DOWN-REGULATION; GLIOMA-CELLS; PHARMACOLOGICAL CHARACTERIZATION; PHOSPHOINOSITIDE HYDROLYSIS; GENE-EXPRESSION; RELEASE; RAT; ASTROCYTES; BIOSYNTHESIS; ACTIVATION AB Endothelin-1 (ET-1) induced a time- and dose-dependent increase in the levels of mRNA of m(2)- and m(3)-muscarinic acetylcholine receptors (mAChRs) in cultured cerebellar granule cells. The levels of immunoprecipitable m(3)-mAChR protein and total mAChR binding sites were also increased by ET-1 treatment. The up-regulation of m(2)- and m(3)-mAChR mRNA was blocked by phorbol ester pretreatment to inhibit ET-1-stimulated phosphoinositide hydrolysis and was preceded by an increase in c-fos mRNA levels. Treatments that prevented ET-1-induced c-fos mRNA increase also abolished the subsequent m(2)- and m(3)-mAChR mRNA up-regulation, suggesting that c-Fos protein is involved in the ET-1-induced mAChR expression. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 24 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 18 PY 1994 VL 348 IS 3 BP 263 EP 267 DI 10.1016/0014-5793(94)00611-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NY712 UT WOS:A1994NY71200009 PM 8034051 ER PT J AU SALLIE, R AF SALLIE, R TI UNTITLED SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Letter ID CHRONIC HEPATITIS-C; CONTROLLED TRIAL; INTERFERON RP SALLIE, R (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JUL 18 PY 1994 VL 161 IS 2 BP 169 EP 170 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NY048 UT WOS:A1994NY04800016 PM 8080533 ER PT J AU BOICE, J LINET, M AF BOICE, J LINET, M TI CHERNOBYL, CHILDHOOD-CANCER, AND CHROMOSOME-21 SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RADIATION RP BOICE, J (reprint author), NCI, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20892 USA. NR 13 TC 21 Z9 21 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUL 16 PY 1994 VL 309 IS 6948 BP 139 EP 140 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NY229 UT WOS:A1994NY22900001 PM 7741834 ER PT J AU GOTOH, M BARNES, CN KOVAC, P AF GOTOH, M BARNES, CN KOVAC, P TI SYNTHESIS OF LIGANDS RELATED TO THE VIBRIO-CHOLERAE O-SPECIFIC ANTIGEN .2. IMPROVED SYNTHESIS AND THE CRYSTAL-STRUCTURE OF METHYL 4,6-DIDEOXY-4-(3-DEOXY-L-GLYCERO-TETRONAMIDO)-ALPHA-D-MANNOPYRANOSIDE, THE METHYL ALPHA-GLYCOSIDE OF THE INTRACATENARY REPEATING UNIT OF THE O-POLYSACCHARIDE OF VIBRIO-CHOLERAE O/1 SO CARBOHYDRATE RESEARCH LA English DT Article AB The crude product of deamination of the commercially available L-homoserine was acetylated and the 2-O-acetyl-3-deoxy-L-glycero-tetronolactone (18) formed was used to N-acylate methyl perosaminide (methyl 4-amino-4,6-dideoxy-alpha-D-mannopyranoside, 12) and its 2,3-O-isopropylidene derivative. The major product isolated from the reaction was the crystalline methyl 4-(4-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-alpha-D-manno-pyranoside (1, 70-75%) resulting from acetyl group migration in the initially formed 2'-O-acetyl derivative. O-Deacetylation of 1 gave the title amide 2. Compound 2, obtained crystalline for the first time, was fully characterized, and its crystal structure was determined. Deoxytetronamido derivatives diastereomeric with 1 and 2, respectively, were obtained by the acylation of 12 with 2-O-acetyl-3-deoxy-D-glycero-tetronolactone (prepared from D-homoserine), and subsequent deacetylation. Structures of several byproducts of the reaction of 12 with 18 have been deduced from their spectral characteristics. Since these byproducts were various O-acetyl derivatives of 2, the title compound could be obtained in similar to 90% yield by deacetylating (Zemplen) the crude mixture of N-acylation products, followed by chromatography. C1 NIDDK,BETHESDA,MD 20892. UNIV MISSOURI,DEPT CHEM,COLUMBIA,MO 65211. NR 15 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 16 PY 1994 VL 260 IS 2 BP 203 EP 218 DI 10.1016/0008-6215(94)84039-3 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NX217 UT WOS:A1994NX21700004 PM 7520833 ER PT J AU STARK, AA PAGANO, DA GLASS, G KAMINBELSKY, N ZEIGER, E AF STARK, AA PAGANO, DA GLASS, G KAMINBELSKY, N ZEIGER, E TI THE EFFECTS OF ANTIOXIDANTS AND ENZYMES INVOLVED IN GLUTATHIONE METABOLISM ON MUTAGENESIS BY GLUTATHIONE AND L-CYSTEINE SO MUTATION RESEARCH LA English DT Article DE SALMONELLA; THIOLS; GLUTATHIONE; CYSTEINE; FREE RADICALS; ANTIOXIDANTS ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; SISTER-CHROMATID EXCHANGES; SALMONELLA-TYPHIMURIUM; LIPID-PEROXIDATION; FREE-RADICALS; AMES TEST; MUTAGENICITY; OXYGEN; RELEVANCE; CELLS AB The effects of small molecular weight antioxidants and antioxidant enzymes on the mutagenicities of glutathione (GSH) and L-cysteine were studied in Salmonella typhimurium strain TA102. GSH and cysteine mutagenesis were inhibited by antioxidants and radical scavengers such as alpha-tocopherol, Trolox C, butylated hydroxyanisole (BHA), and retinyl acetate. Superoxide dismutase (SOD) had no effect, but catalase and horseradish peroxidase (HRP) inhibited mutagenesis. The heat-denatured enzymes had no effect on mutagenesis. Cysteine mutagenesis was enhanced by native and by heat-denatured rat-kidney post-mitochondrial supernatant, and by ferric ions. H2O2 and the H2O2-generating system of glucose-glucose oxidase (GOX) were mutagenic in TA102. Synergistic increases in mutagenesis were obtained in systems containing combinations of GSH or cysteine, with either H2O2 or the H2O2-generating system of glucose-GOX. GSH peroxidase (GPX) had no effect on mutagenesis of GSH or of H2O2, whereas the synergistic increase in mutagenesis by a combination of GSH and H2O2 was effectively inhibited by GPX. The results suggest strongly that, at least in biochemically-defined systems, GSH and cysteine mutagenesis are oxidative in nature, and involve reactive forms of oxygen and/or other radicals. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP STARK, AA (reprint author), TEL AVIV UNIV,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 30 TC 23 Z9 23 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL 16 PY 1994 VL 308 IS 2 BP 215 EP 222 DI 10.1016/0027-5107(94)90156-2 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NX934 UT WOS:A1994NX93400011 PM 7518048 ER PT J AU CHARLES, MA PETTITT, DJ HANSON, RL BENNETT, PH SAAD, MF LIU, QZ KNOWLER, WC AF CHARLES, MA PETTITT, DJ HANSON, RL BENNETT, PH SAAD, MF LIU, QZ KNOWLER, WC TI FAMILIAL AND METABOLIC FACTORS RELATED TO BLOOD-PRESSURE IN PIMA INDIAN CHILDREN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CHILD; DIABETES MELLITUS, NON-INSULIN-DEPENDENT; FAMILY CHARACTERISTICS; GLUCOSE; HYPERTENSION; INSULIN; OBESITY ID CARDIOVASCULAR RISK-FACTORS; SCHOOL-AGE CHILDREN; GLUCOSE-INTOLERANCE; INSULIN SENSITIVITY; PLASMA-GLUCOSE; HYPERTENSION; AGGREGATION; OBESITY; VARIABLES; NIDDM AB High blood pressure, abnormal glucose tolerance, and obesity are frequently associated with each other, but the mechanism of these associations is poorly understood. Studying them in children may help in understanding the pathogenesis of hypertension. Blood pressure, height, weight, and plasma glucose and serum insulin concentrations during a 75-g oral glucose tolerance test were measured in 1,698 Pima Indian children aged 6-17 years who participated in an ongoing epidemiologic study. Weight relative to height was used as an index of obesity. The parents of many of the children were also examined. Fasting and 2-hour glucose and insulin concentrations, adjusted for age, sex, and relative weight, were positively related to systolic blood pressure but not to diastolic blood pressure. Relative weight, 2-hour glucose, and fasting insulin concentrations were independently and significantly associated with systolic blood pressure in a stepwise regression analysis that included age and sex. After parental hypertension was taken into account, maternal but not paternal non-insulin-dependent diabetes mellitus, controlled for the child's relative weight and glucose and insulin concentrations, was significantly associated with higher blood pressure in children. The stronger association with maternal diabetes suggests a greater sharing of environmental factors between mother and child than between father and child, but familial similarities in obesity and glucose and insulin concentrations, the diabetic intrauterine milieu, and shared environmental factors probably all contribute to this association. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 41 TC 29 Z9 31 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1994 VL 140 IS 2 BP 123 EP 131 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NX125 UT WOS:A1994NX12500004 PM 8023801 ER PT J AU WILCOX, AJ AF WILCOX, AJ TI ARE FEMALE SMOKERS AT HIGHER RISK FOR LUNG-CANCER THAN MALE SMOKERS - A CASE-CONTROL ANALYSIS BY HISTOLOGIC TYPE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 1 TC 7 Z9 7 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1994 VL 140 IS 2 BP 186 EP 186 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NX125 UT WOS:A1994NX12500010 PM 8023807 ER PT J AU WHITCUP, SM SALVO, EC NUSSENBLATT, RB AF WHITCUP, SM SALVO, EC NUSSENBLATT, RB TI COMBINED CYCLOSPORINE AND CORTICOSTEROID-THERAPY FOR SIGHT-THREATENING UVEITIS IN BEHCETS-DISEASE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR INFLAMMATORY DISEASE; EXPERIMENTAL AUTOIMMUNE UVEITIS; LOW-DOSE CYCLOSPORINE; CHLORAMBUCIL; AZATHIOPRINE AB Behcet's disease is a multisystem disorder that may cause profound ocular inflammation and blindness. We reviewed 19 patients with severe ocular Behcet's disease treated with combined cyclosporine and corticosteroid therapy. Previous treatment with corticosteroids alone failed to control the uveitis in all patients. Ten patients were given cyclosporine therapy alone (mean dosage, 8.6 mg/kg of body weight per day), and nine patients were given lower dosages of cyclosporine (mean dosage, 6.2 mg/kg of body weight per day) in combination with prednisone (mean dosage, 29.4 mg per day). The mean follow-up on therapy was 51 months. After three months of therapy, a trend toward greater improvement in visual acuity was noted in patients treated with combined cyclosporine and prednisone compared to those receiving cyclosporine alone (17.8 letters vs 10.2 letters, P = .2379), but after one year little difference was observed in the improvement between the two groups (5.8 letters vs 3.3 letters, P = .7984). However, a trend toward greater renal toxicity was seen in patients treated with cyclosporine alone after both three months and one year of therapy. Because of either a suboptimal therapeutic response or adverse effects, all patients treated with cyclosporine alone at baseline had prednisone added to their regimen after a mean time of 23.5 months. Overall, visual acuity remained stable or improved in 28 of 37 eyes (75.7%) over the course of therapy. These data suggest that combined cyclosporine and prednisone therapy is an effective treatment for Behcet's uveitis and may be less toxic than therapy with cyclosporine alone. A prospective, randomized trial with a larger sample size is needed to provide definitive data. RP WHITCUP, SM (reprint author), NEI,CLIN BRANCH,BLDG 10,RM 10N 202,BETHESDA,MD 20892, USA. NR 26 TC 69 Z9 72 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 JUL 15 PY 1994 VL 118 IS 1 BP 39 EP 45 PG 7 WC Ophthalmology SC Ophthalmology GA NW009 UT WOS:A1994NW00900006 PM 8023874 ER PT J AU STEIN, DS GRAHAM, NMH PARK, LP HOOVER, DR PHAIR, JP DETELS, R HO, M SAAH, AJ AF STEIN, DS GRAHAM, NMH PARK, LP HOOVER, DR PHAIR, JP DETELS, R HO, M SAAH, AJ TI THE EFFECT OF THE INTERACTION OF ACYCLOVIR WITH ZIDOVUDINE ON PROGRESSION TO AIDS AND SURVIVAL - ANALYSIS OF DATA IN THE MULTICENTER AIDS COHORT STUDY SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; DOSE ZIDOVUDINE; CLINICAL COURSE; HOMOSEXUAL MEN; INFECTION; COMPLEX; HIV-1; PREVALENCE; EFFICACY AB Objective: To examine the effect of acyclovir use on disease progression and survival in human immunodeficiency virus (HIV)-seropositive persons treated with zidovudine. Setting: Four university-based or -affiliated clinics. Design: Prospective cohort study of homosexual and bisexual men with semi-annual follow-up. Intent-to-treat Cox models were fit to determine the relation between the use of acyclovir (modeled as a time-dependent covariate) and disease progression, controlling for baseline and time-dependent clinical and laboratory prognostic variables. The acquired immunodeficiency syndrome (AIDS)-free duration and survival time were calculated from the first use of zidovudine. Analysis included study visits 7 to 17 (from 1987 to 1992). Patients: 786 HIV-seropositive participants in the Multicenter AIDS Cohort Study who began zidovudine therapy before a clinical diagnosis of AIDS; of these, 515 subsequently received acyclovir. Participants were asked at each visit whether they had ''used any medication for health reasons not related to AIDS or if they had taken any medication to help fight AIDS or the HIV virus''; 488 patients indicated acyclovir use under either or both questions, and 242 patients indicated only the latter use. Results: The use of acyclovir for any indication was not associated with an effect on progression to AIDS but was associated with a 26% decrease in the risk for death (relative hazard, 0.74; P = 0.07). The use of acyclovir for HIV infection was also not associated with an effect on progression to AIDS but was associated with a 36% decrease in the risk for death (relative hazard, 0.64; P = 0.01). To further investigate these findings, we examined dose, constancy, and timing of acyclovir use. The median daily dose of acyclovir used for HIV infection was between 600 and 800 mg. No apparent dose effect on survival was found. Longer uninterrupted use of acyclovir for any indication was associated with an 18% decrease in the risk for death for three or more consecutive visits (relative hazard, 0.82; P = 0.23), a 28% decrease for four or more consecutive visits (relative hazard, 0.72; P = 0.09), and a 7% decrease per visit based on the cumulative number of visits while the patient received acyclovir (relative hazard, 0.93 per visit increase; P = 0.03). Use of acyclovir for any indication and use of acyclovir for HIV infection were each associated with a 44% decreased probability of death if the drug was used after AIDS developed (P = 0.007 and P = 0.005, respectively) but not before. To further investigate the prolongation of survival, two landmark analyses were done. The first analysis began at a landmark of 1 year after initiation of zidovudine therapy and compared three groups of patients: those who used acyclovir at or before this landmark, those who had never started acyclovir or started the drug after the landmark, and those who had never used acyclovir. The 90% survival times were 1325, 1059, and 982 days, respectively. The second analysis began at a landmark of developing either a CD4 count less than 50 cells/mu L or clinical AIDS. The 90% survival times for the three groups were 398, 261,and 176 days, respectively. C1 NIAID,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NORTHWESTERN UNIV,CHICAGO,IL. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV PITTSBURGH,PITTSBURGH,PA. FU NIAID NIH HHS [UO1-AI-35041, UO1-AI-35039, UO1-AI-35040] NR 37 TC 75 Z9 75 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 1994 VL 121 IS 2 BP 100 EP 108 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA NW186 UT WOS:A1994NW18600004 PM 8017721 ER PT J AU WELSH, CJ YEH, GC PHANG, JM AF WELSH, CJ YEH, GC PHANG, JM TI INCREASED PHOSPHOLIPASE-D ACTIVITY IN MULTIDRUG-RESISTANT BREAST-CANCER CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID D-MEDIATED HYDROLYSIS; SMOOTH-MUSCLE CELLS; SIGNAL TRANSDUCTION; P-GLYCOPROTEIN; GROWTH-FACTOR; PHOSPHATIDYLETHANOLAMINE; DIACYLGLYCEROL; MECHANISMS AB An adriamycin-resistant MCF-7 cell line (300-fold increased resistance vs. wild type MCF-7) showed an increased phorbol ester-stimulated phospholipase D activity of approximately 4-6 times over that found in wild type cells. Phospholipase D activity was assessed by monitoring the mass of phorbol ester-induced phosphatidylethanol. The cellular phospholipase D activity was time- and phorbol ester-concentration-dependent and was obvious whether measured as an increase in the mass of PEt or in the production of H-3-labeled phosphatidylethanol in cells prelabeled with [H-3]myristic acid. Phorbol ester also stimulated increases in the production of the mass of cellular diacylglycerol and phosphatidic acid in the adriamycin-resistant cells vs. the wildtype cells. Tests with a series of drug-resistant MCF-7 cell lines revealed a positive correlation between increased drug resistance and phorbol ester-stimulated phospholipase D activity. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 25 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1994 VL 202 IS 1 BP 211 EP 217 DI 10.1006/bbrc.1994.1914 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX142 UT WOS:A1994NX14200030 PM 8037714 ER PT J AU MASOOD, R LUNARDIISKANDAR, Y MOUDGIL, T ZHANG, Y LAW, RE HUANG, CL PURI, RK LEVINE, AM GILL, PS AF MASOOD, R LUNARDIISKANDAR, Y MOUDGIL, T ZHANG, Y LAW, RE HUANG, CL PURI, RK LEVINE, AM GILL, PS TI IL-10 INHIBITS HIV-1 REPLICATION AND IS INDUCED BY TAT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS FACTOR-ALPHA; LYMPHOBLASTOID CELL-LINE; GENE-EXPRESSION; INFECTION; TRANSCRIPTION; ACTIVATION; TYPE-1; AIDS AB Interleukin 10 (IL-10) is produced by T(H)2 lymphocytes and regulates both lymphoid and myeloid cells. In the present study we demonstrate that IL-10 is expressed and produced spontaneously in the peripheral blood mononuclear cells (PBMCs) of all HIV-1 infected individuals tested, 3 of 19 cases of HIV-negative lymphoma and none of five healthy controls. IL-10 mRNA was detectable in both monocytes/macrophages and T lymphocytes isolated from PBMCs of HIV infected patients. We have also shown that infection of promonocytic (U937) and T (H9) cell lines with HIV stimulates IL-10 secretion. Furthermore, a T cell line (H9) stably transfected with a HIV tat expression-vector secreted higher levels of IL-10. We have also demonstrated that rhIL-10 inhibited HIV-1 replication in infected monocytes and PBMCs in a dose dependent manner. IL-10 may thus participate in long latency between HIV-1 infection and development of AIDS. (C) 1994 Academic Press, Inc. C1 UNIV SO CALIF,DEPT MED,LOS ANGELES,CA 90033. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LAB INC,KENSINGTON,MD 20895. US FDA,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20014. FU NCI NIH HHS [CA51621, CA55510]; NHLBI NIH HHS [HL48499] NR 23 TC 60 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1994 VL 202 IS 1 BP 374 EP 383 DI 10.1006/bbrc.1994.1938 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX142 UT WOS:A1994NX14200054 PM 8037735 ER PT J AU WEEKS, BS NOMIZU, M OTAKA, A WESTON, CA OKUSU, A TAMAMURA, H MATSUMOTO, A YAMAMOTO, N FUJII, N AF WEEKS, BS NOMIZU, M OTAKA, A WESTON, CA OKUSU, A TAMAMURA, H MATSUMOTO, A YAMAMOTO, N FUJII, N TI LYMPHOCYTES AND PROMONOCYTES ATTACH TO THE SYNTHETIC [TYR(5,12),LYS(7)]-POLYPHEMUSIN-II PEPTIDE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HORSESHOE-CRAB HEMOCYTES; TACHYPLESIN-I; POLYPHEMUSIN-I; CELL-LINES; HTLV-III AB The [Tyr(5,12), Lys(7)]-polyphemusin II peptide (T22) has been shown to inhibit HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication is not known but may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that three human immunocyte cell lines (H9, Jurkat, and U-937) attach to T22. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA),has been shown to activate intracellular protein kinase C and to stimulate lymphocyte attachment to various substrates through specific cell surface receptors. Here we find that TPA treatment enhances attachment of the immunocytes to T22 by three- to four-fold. These data demonstrate that T22 binds to immunocyte cell surfaces and support the hypothesis that T22 may inhibit HIV-1 replication by competing with the virus for a common cell surface receptor(s). (C) 1994 Academic Press, Inc. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. KYOTO UNIV,FAC PHARMACEUT SCI,SAKYO KU,KYOTO 606,JAPAN. SEIKAGAKU CORP,CHUO KU,TOKYO 103,JAPAN. TOKYO MED & DENT UNIV,SCH MED,DEPT MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. RP WEEKS, BS (reprint author), HAMILTON COLL,DEPT BIOL,198 COLL HILL RD,CLINTON,NY 13323, USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1994 VL 202 IS 1 BP 470 EP 475 DI 10.1006/bbrc.1994.1952 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX142 UT WOS:A1994NX14200068 PM 8037749 ER PT J AU DING, M BECK, RJ KELLER, CJ FENTON, RG AF DING, M BECK, RJ KELLER, CJ FENTON, RG TI CLONING AND ANALYSIS OF MAGE-1-RELATED GENES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; MAGE-1; ANTIGEN AB The spectrum of MAGE gene expression in the human melanoma cell line DM150 was examined using reverse transcription polymerase chain reaction and cDNA cloning. We have examined isolated five full-length cDNAs from DM150 which were identified as MAGE-1, MAGE-3, MAGE-12 and two previously undescribed MAGE, MAGE-3b and MAGE-X2. DNA sequence analysis of the coding regions of the MAGE-3b and MAGE-X2 genes revealed 83% and 88% identity with MAGE-1, while MAGE-3b was 98% homologous with the full length MAGE-3 clone. The predicted amino acid sequences of MAGE-X2 and MAGE-3b contain consensus HLA-A1 peptide binding motifs, suggesting that, like MAGE-1, they may code for tumor- associated antigens. In addition, a nonamer peptide encoded by both the MAGE-3 and MAGE-12 genes was shown by direct binding studies to contain an aggretope for HLA-A2. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,CLIN RES BRANCH,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV P,FREDERICK,MD 21702. NR 14 TC 18 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1994 VL 202 IS 1 BP 549 EP 555 DI 10.1006/bbrc.1994.1963 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX142 UT WOS:A1994NX14200079 PM 8037761 ER PT J AU MAHER, F SIMPSON, IA AF MAHER, F SIMPSON, IA TI THE GLUT3 GLUCOSE-TRANSPORTER IS THE PREDOMINANT ISOFORM IN PRIMARY CULTURED NEURONS - ASSESSMENT BY BIOSYNTHETIC AND PHOTOAFFINITY-LABELING SO BIOCHEMICAL JOURNAL LA English DT Article ID BLOOD-BRAIN-BARRIER; RAT-BRAIN; ADENYLYL CYCLASE; GENE-EXPRESSION; XENOPUS OOCYTES; 3T3-L1 CELLS; GLIAL-CELLS; INSULIN; ERYTHROCYTE; FORSKOLIN AB Cerebellar granule neurons in primary culture express increasing levels of two glucose transporter isoforms, GLUT1 and GLUT3, as they differentiate in vitro. We have determined the relative abundance of GLUT1 and GLUT3 in these neurons by three different labelling methods. (1) Photoaffinity cell surface labelling of neurons with an impermeant bis-mannose photolabel revealed 6-10-fold more GLUT3 than GLUT1 and dissociation constants (K-d) for the photolabel of 55-68 mu M (GLUT3) and 146-169 mu M (GLUT1). Binding to both transporters was inhibited by cytochalasin B. (2) Photoaffinity labelling of neuronal membranes with a permeant forskolin derivative showed 5.5-8-fold more GLUT3 than GLUT1, whereas in rat brain membranes containing both neuronal and glial membranes, GLUT3 and GLUT1 were detected in similar proportions. (3) Biosynthetic labelling of neurons with [S-35]methionine and [S-35]cysteine showed GLUT3 to be 6-10-fold more abundant than GLUT1. Thus GLUT3 is quantitatively the predominant glucose-transport isoform in cultured cerebellar granule neurons. RP MAHER, F (reprint author), NIDDK,EDMNS,BLDG 10,ROOM 5N102,BETHESDA,MD 20892, USA. NR 38 TC 48 Z9 50 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1994 VL 301 BP 379 EP 384 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA559 UT WOS:A1994PA55900012 PM 8042980 ER PT J AU DELZOMPO, M BOCCHETTA, A LOVISELLI, A MARTINO, E POST, RM KETTER, TA AF DELZOMPO, M BOCCHETTA, A LOVISELLI, A MARTINO, E POST, RM KETTER, TA TI THYROID-FUNCTION DURING CARBAMAZEPINE SO BIOLOGICAL PSYCHIATRY LA English DT Note DE CARBAMAZEPINE; AFFECTIVE DISORDER; THYROID HORMONE; THYROID-STIMULATING HORMONE; FREE TRIIODOTHYRONINE; IODINASE ID ANTICONVULSANT DRUGS; EPILEPTIC PATIENTS; LITHIUM TREATMENT; FUNCTION TESTS; THYROXINE; TRIIODOTHYRONINE; PHENYTOIN; ABNORMALITIES; HORMONES; CHILDREN C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV CAGLIARI,INST INTERNAL MED,CAGLIARI,ITALY. RP DELZOMPO, M (reprint author), UNIV CAGLIARI,BB BRODIE DEPT NEUROSCI,VIA PORCELL 4,I-09124 CAGLIARI,ITALY. OI BOCCHETTA, ALBERTO/0000-0003-2601-5529 NR 18 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1994 VL 36 IS 2 BP 135 EP 136 DI 10.1016/0006-3223(94)91194-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NX838 UT WOS:A1994NX83800009 PM 7948446 ER PT J AU PEARCE, SFA WU, J SILVERSTEIN, RL AF PEARCE, SFA WU, J SILVERSTEIN, RL TI A CARBOXY-TERMINAL TRUNCATION MUTANT OF CD36 IS SECRETED AND BINDS THROMBOSPONDIN - EVIDENCE FOR A SINGLE TRANSMEMBRANE DOMAIN SO BLOOD LA English DT Note ID FALCIPARUM-INFECTED ERYTHROCYTES; GLYCOPROTEIN-IV CD36; PARASITIZED ERYTHROCYTES; MEDIATES CYTOADHERENCE; MONOCLONAL-ANTIBODY; SIGNAL TRANSDUCTION; COMPLEX-FORMATION; MEMBRANE-PROTEIN; TISSUE ACTIVATOR; MELANOMA-CELLS C1 CORNELL UNIV,COLL MED,NIH SCOR THROMBOSIS,NEW YORK,NY 10021. RP PEARCE, SFA (reprint author), CORNELL UNIV,COLL MED,DEPT MED,DIV HEMATOL ONCOL,ROOM C606,1300 YORK AVE,NEW YORK,NY 10021, USA. FU NHLBI NIH HHS [HL 46403, HL 18828, HL 42540] NR 38 TC 54 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1994 VL 84 IS 2 BP 384 EP 389 PG 6 WC Hematology SC Hematology GA NX154 UT WOS:A1994NX15400004 PM 7517712 ER PT J AU WALSH, CE GROMPE, M VANIN, E BUCHWALD, M YOUNG, NS NIENHUIS, AW LIU, JM AF WALSH, CE GROMPE, M VANIN, E BUCHWALD, M YOUNG, NS NIENHUIS, AW LIU, JM TI A FUNCTIONALLY ACTIVE RETROVIRUS VECTOR FOR GENE-THERAPY IN FANCONI-ANEMIA GROUP-C SO BLOOD LA English DT Article C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. HOSP SICK CHILDREN, DEPT GENET, TORONTO M5G 1X8, ON, CANADA. GENET THERAPY INC, GAITHERSBURG, MD USA. NR 25 TC 70 Z9 72 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1994 VL 84 IS 2 BP 453 EP 459 PG 7 WC Hematology SC Hematology GA NX154 UT WOS:A1994NX15400014 PM 7517716 ER PT J AU DICHEK, DA LEE, SW NGUYEN, NH AF DICHEK, DA LEE, SW NGUYEN, NH TI CHARACTERIZATION OF RECOMBINANT PLASMINOGEN-ACTIVATOR PRODUCTION BY PRIMATE ENDOTHELIAL-CELLS TRANSDUCED WITH RETROVIRAL VECTORS SO BLOOD LA English DT Article ID MEDIATED GENE-TRANSFER; MESSENGER-RNA LEVELS; FIBRINOLYTIC-ACTIVITY; INHIBITOR TYPE-1; LYMPHOCYTES-T; EXPRESSION; UROKINASE; PLASMA; RESISTANT; INDUCTION RP DICHEK, DA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D-18,BETHESDA,MD 20892, USA. NR 46 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1994 VL 84 IS 2 BP 504 EP 516 PG 13 WC Hematology SC Hematology GA NX154 UT WOS:A1994NX15400021 PM 8025279 ER PT J AU AUGUST, EM NGUYEN, T MALINOWSKI, NM CYSYK, RL AF AUGUST, EM NGUYEN, T MALINOWSKI, NM CYSYK, RL TI NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND TUMOR PROGRESSION - INHIBITION OF FIBROBLAST HYALURONIC-ACID PRODUCTION BY INDOMETHACIN AND MEFENAMIC-ACID SO CANCER LETTERS LA English DT Article DE HYALURONIC ACID; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FIBROBLAST; TUMOR PROGRESSION ID COLORECTAL-CANCER; PROSTAGLANDIN SYNTHESIS; COLON CANCER; ASPIRIN USE; METASTASIS; CARCINOMA; RISK; MICE; CARCINOGENESIS; FLURBIPROFEN AB The antitumor effects of non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in a variety of both clinical and experimental settings, although the mechanisms responsible remain unclear. In the present study, we show that the NSAIDs indomethacin and mefenamic acid inhibit the calf serum-stimulated production of hyaluronic acid (HA) in murine Swiss 3T3 fibroblasts, at concentrations where DNA synthesis is unaffected. HA is an extracellular matrix glycosaminoglycan associated with cell migration and tumor invasion. Our data suggest that one mechanism whereby NSAIDs inhibit tumor progression may be to inhibit the synthesis of HA by host fibroblasts, and that the eicosenoid pathway may represent an important control point in the growth-factor-mediated production of HA in fibroblasts. Thus the use of an agent which inhibits HA synthesis may be a novel approach to alter the invasive and metastatic properties of tumor cells in a non-cytotoxic fashion. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NR 37 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 15 PY 1994 VL 82 IS 1 BP 49 EP 54 PG 6 WC Oncology SC Oncology GA PH103 UT WOS:A1994PH10300007 PM 8033068 ER PT J AU LEYTON, J MANYAK, MJ MUKHERJEE, AB MIELE, L MANTILE, G PATIERNO, SR AF LEYTON, J MANYAK, MJ MUKHERJEE, AB MIELE, L MANTILE, G PATIERNO, SR TI RECOMBINANT HUMAN UTEROGLOBIN INHIBITS THE IN-VITRO INVASIVENESS OF HUMAN METASTATIC PROSTATE TUMOR-CELLS AND THE RELEASE OF ARACHIDONIC-ACID STIMULATED BY FIBROBLAST-CONDITIONED MEDIUM SO CANCER RESEARCH LA English DT Note ID CLARA CELL; RABBIT UTEROGLOBIN; 10-KDA PROTEIN; BREAST-CANCER; CARCINOMA; EICOSANOIDS; EXPRESSION; INVASION; WASHINGS; LECTURE AB Uteroglobin (UG) is a potent immunomodulatory and antiinflammatory secretory protein with high levels detected in human prostate tissue. We used three human prostate cancer cell lines (DU-145, PC3-M, and LNCaP) to test the hypothesis that UG may modulate invasiveness of prostatic carcinoma cells in the Boyden chamber assay for invasion through a reconstituted basement membrane preparation. Fibroblast-conditioned medium was used as the chemoattractant. The most invasive cell line was DU-145, followed by PC3-M, whereas the androgen-dependent LNCaP cell line exhibited extremely low invasive potential. Pretreatment of DU-145 and PC3-M cells for 24 h with 0.01, 0.1, or 1.0 mu M recombinant UG had no effect on basal invasiveness but inhibited fibroblast-conditioned medium-stimulated invasion in a dose-dependent manner, reaching up to 60.2 and 87.9% inhibition of DU-145 and PC3-M, respectively. UG had no effect on either cell-reconstituted basement membrane adhesion or simple chemotaxis in the absence of reconstituted basement membrane. UG also strongly inhibited the biphasic release of [C-14]-labeled arachidonic acid from fibroblast-conditioned medium-stimulated DU-145 cells. These results suggest that UG may modulate prostate tumor cell invasiveness and that the mechanism may include inhibition of the arachidonic acid signal cascade. C1 GEORGE WASHINGTON UNIV, MED CTR, DEPT PHARMACOL, WASHINGTON, DC 20037 USA. GEORGE WASHINGTON UNIV, MED CTR, DEPT UROL, WASHINGTON, DC 20037 USA. NICHHD, HUMAN GENET BRANCH, DEV GENET SECT, BETHESDA, MD 20892 USA. NR 29 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1994 VL 54 IS 14 BP 3696 EP 3699 PG 4 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600011 PM 8033085 ER PT J AU ENDO, H SCHUT, HAJ SNYDERWINE, EG AF ENDO, H SCHUT, HAJ SNYDERWINE, EG TI MUTAGENIC SPECIFICITY OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE IN THE SUPF SHUTTLE VECTOR SYSTEM SO CANCER RESEARCH LA English DT Article ID CARCINOGENIC HETEROCYCLIC AMINES; CIGARETTE-SMOKE CONDENSATE; ESCHERICHIA-COLI; MUTATIONAL SPECIFICITY; XERODERMA-PIGMENTOSUM; COOKED FOOD; DNA ADDUCTS; HUMAN-CELLS; RAS GENE; PLASMID AB 2 Amino-3-methylimidazo [4,5-f]quinoline (IQ) and 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amine mutagens/carcinogens formed from the cooking of meat. Here we used the pSP189 shuttle vector developed by Parris and Seidman (Gene, 117: 1-5, 1992) to study and compare the mutation spectre induced by these compounds. pSP189 was adducted by reaction with the N-acetoxy derivatives of IQ or PhIP. P-32-Postlabeling analysis was used to measure the C-g-guanine adduct level and the total adduct levels formed in the plasmid. Plasmids were replicated and mutagenized in repair-proficient [GM0637(SV40)] or repair-deficient XP12Be(SV40)1 human fibroblasts. Resulting inactivation mutations in the supF gene were determined by the formation of white or light blue colonies on indicator bacteria (carrying a lacZ amber mutation) and cycle sequencing. With both compounds in either cell line, 85-93 % of the mutations induced were base substitutions and the remainder of the mutations were base deletions. The majority of the substitution mutations involved a single base, and nearly all base substitution mutations (>97%) were at guanine. This latter finding is consistent with the results from P-32-postlabeling showing that both compounds adduct to the guanine base with the major adduct being formed at the C,-guanine position. The predominant mutation found with IQ and PhIP in either cell line was G:C to T:A transversion, followed by G:C to A:T transition, and then G:C to C:G transversion; these mutations accounted for 59-72%, 19-27%, and 6-14% of total base substitution mutations, respectively. There was a preference seen with both compounds to induce mutations at a guanine base having a neighboring guanine or cytosine (i.e., GG and GC sites). However, despite the striking similarity in the kinds of base substitution mutations induced by IQ and PhIP, their mutation spectra were distinct. For example, in repair-proficient cells, 26% of the mutations induced with PhIP, but not with IQ, also involved a GA site, containing the Ei-base pair sequence 5 '-GCAGA3 '. Mutation spectra for IQ and PhIP were also different between repair-deficient and repair-proficient cells. The findings shown here may serve to be predictive of the kinds of mutations induced by the adducts of IQ and PhIP in oncogenes and tumor suppressor genes altered during heterocyclic amine-induced carcinogenesis. C1 NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. NR 50 TC 45 Z9 45 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 JUL 15 PY 1994 VL 54 IS 14 BP 3745 EP 3751 PG 7 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600021 PM 8033094 ER PT J AU ARTEAGA, CL WINNIER, AR POIRIER, MC LOPEZLARRAZA, DM SHAWVER, LK HURD, SD STEWART, SJ AF ARTEAGA, CL WINNIER, AR POIRIER, MC LOPEZLARRAZA, DM SHAWVER, LK HURD, SD STEWART, SJ TI P185(C-ERBB-2) SIGNALING ENHANCES CISPLATIN-INDUCED CYTOTOXICITY IN HUMAN BREAST-CARCINOMA CELLS - ASSOCIATION BETWEEN AN ONCOGENIC RECEPTOR TYROSINE KINASE AND DRUG-INDUCED DNA-REPAIR SO CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN OVARIAN-CANCER; TUMOR-NECROSIS-FACTOR; HER-2 NEU ONCOGENE; CIS-DIAMMINEDICHLOROPLATINUM; EGF RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; PROGNOSTIC-SIGNIFICANCE; MONOCLONAL-ANTIBODIES; INCREASED SENSITIVITY AB The c-erbB-2 (HER-2/neu) protooncogene encodes an M(r) 185,000 transmembrane glycoprotein with intrinsic tyrosine kinase activity. Agonistic antibodies against p185(c-erbB-2) enhance the cytotoxic effect of the DNA alkylator, cisplatin, against c-erbB-2-overexpressing human carcinoma cells (Hancock et al., Cancer Res., 51: 4575-4580, 1991). We have studied the possible association between receptor signal transduction and cisplatin-mediated cytotoxicity utilizing the SKBR-3 human breast cancer cell line and the anti-p185 TAb 250 IgG1. TAb 250 induced tyrosine phosphorylation of p185 and the receptor substrate phospholipase C-gamma 1, as well as rapid association of these molecules in vivo. Simultaneously with phosphorylation, phospholipase C-gamma 1 catalytic activity measured in a [H-3]phosphatidylinositol-4,5-bisphosphate hydrolysis assay was increased 61 +/- 12% above control. Preincubation of SKBR-3 cells with the tyrosine kinase inhibitor tyrphostin 50864-2 abrogated the enhancement of drug-mediated cell kill induced by TAb 250. The supraadditive drug/antibody effect was not seen in SKBR-3 cells with TAb 263, an anti-p185 IgG1 that does not induce receptor signaling or with TAb 250 in MDA-468 breast cancer cells which do not overexpress c-erbB-2. In addition, transforming growth factor-alpha increased cisplatin-induced cytotoxicity against NIH 3T3 cells overexpressing an epidermal growth factor receptor/c-erbB-2 chimera. Cellular uptake or efflux of [Pt-195m]cisplatin by SKBR-3 cells was not altered by TAb 250. Finally, simultaneous treatment of SKBR-3 cells with TAb 250 and cisplatin increased cisplatin/DNA intrastrand adduct formation and delayed the rate of adduct decay. Taken together these data support a direct association between p185(c-erbB-2) signal transduction and inhibition of cisplatin-induced DNA repair. C1 VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT IMMUNOL & MICROBIOL,NASHVILLE,TN 37232. DEPT VET AFFAIRS MED CTR,NASHVILLE,TN 37232. BERLEX BIOSCI,ALAMEDA,CA 94501. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 69 TC 128 Z9 131 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1994 VL 54 IS 14 BP 3758 EP 3765 PG 8 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600023 PM 7913407 ER PT J AU PLOWMAN, J WAUD, WR KOUTSOUKOS, AD RUBINSTEIN, LV MOORE, TD GREVER, MR AF PLOWMAN, J WAUD, WR KOUTSOUKOS, AD RUBINSTEIN, LV MOORE, TD GREVER, MR TI PRECLINICAL ANTITUMOR-ACTIVITY OF TEMOZOLOMIDE IN MICE - EFFICACY AGAINST HUMAN BRAIN-TUMOR XENOGRAFTS AND SYNERGISM WITH 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA SO CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; CYTO-TOXICITY; ALKYLTRANSFERASE ACTIVITY; ALKYLATING-AGENTS; HUMAN-CELLS; IMIDAZOTETRAZINES; SENSITIVITY; LEUKEMIA; REPAIR; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA AB Temozolomide, a methylating agent with clinical activity against brain tumors, demonstrated excellent antitumor activity following p.o. administration to athymic mice bearing human brain tumor xenografts. Is the early stage s.c. implanted SNB-75 astrocytoma model, a 400-mg/kg dose administered on Day 5 produced 10 of 10 Day 54 tumor-free mice. In later staged s.c. U251 and SF-295 glioblastoma models, a single 600-mg/kg dose produced 9 of 10 Day 86 and 2 of 10 Day 40 tumor-free mice, respectively. In the latter group, a tumor growth delay of >315% was attained. Similar levels of activity were attained with equal total doses on schedules of daily for 5 doses and every fourth day for 3 doses. A single 40-mg/kg i,v. dose of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) also demonstrated excellent activity, producing 9 of 10 tumor-free mice in the SNB-75 model and growth delays of 283 and 301% in the U251 and SF-295 models, respectively. Temozolomide was also highly effective against intracerebral implants of the U251 and SF-295 glioblastomas. Administration of either 600 mg/kg on Day 1 or 200 mg/kg on Days 1, 5, and 9 produced 7 of 9 Day 90 tumor-free mice in the U251 model. In the SF-295 model, a single 400-mg/kg dose or three 200-mg/kg doses produced 3 and 4 of 10 Day 90 tumor-free mice, respectively, and prolonged survival by 127%. A single 40-mg/kg i.v. dose of BCNU was more effective than temozolomide in the intracerebral SF 295 model, and less effective in the intracerebral U251 model. The synergistic potential of temozolomide and BCNU in combination was evaluated in an advanced stage s.c. implanted SF-295 model. When temozolomide was administered 2 h after BCNU on a single treatment day, a dramatic synergistic therapeutic effect was observed in two experiments. For example, single agent doses of temozolomide (600 mg/kg) and BCNU (60 mg/kg) and a combination (400 mg/kg + 27 mg/kg) demonstrating equivalent toxicity produced growth delays of 190, 258, and >492% (includes 5 of 10 Day 51 tumor-free mice), respectively. Analysis of the data by a quadratic dose response model indicated synergism with significance at P = 0.0001 in both experiments. Synergism also was demonstrated by the isobole method. The reverse sequence was more toxic, but at lower combination doses a synergistic effect was still observed (P = 0.0001). Using the quadratic model, no confirmed modulation of the antitumor activity of temozolomide was demonstrated by i.p. administration of either 10 or 30 mg/kg O-6-benzylguanine 1 h before or 1 h after temozolomide. These data provide a rationale for the clinical evaluation of temozolomide and BCNU combinations in patients with brain tumors. C1 NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. SO RES INST,BIRMINGHAM,AL 35255. FU NCI NIH HHS [N01-CM-27714, N01-CM-07315] NR 27 TC 91 Z9 91 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1994 VL 54 IS 14 BP 3793 EP 3799 PG 7 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600028 PM 8033099 ER PT J AU SHIMADA, S OGAWA, M TAKAHASHI, M SCHLOM, J GREINER, JW AF SHIMADA, S OGAWA, M TAKAHASHI, M SCHLOM, J GREINER, JW TI MOLECULAR-CLONING AND CHARACTERIZATION OF THE COMPLEMENTARY-DNA OF AN M(R)-110,000 ANTIGEN EXPRESSED BY HUMAN GASTRIC-CARCINOMA CELLS AND UP-REGULATED BY GAMMA-INTERFERON SO CANCER RESEARCH LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODIES; MESSENGER-RNA; RECEPTOR; IDENTIFICATION; DETERMINANTS; SEQUENCES; EPITOPES; PEPTIDE; GENE AB An M(r), 110,000 antigen was initially described in human gastric carcinoma cells by its cross-reactivity with anti-carcinoembryonic antigen (CEA) monoclonal antibodies, as well as the ability of gamma-interferon to increase its level of expression. We describe the molecular cloning and sequence analyses of overlapping clones that constitute a full-length complementary DNA that encodes for the entire M(r) 110,000 molecule. The 1.5-kilobase message encodes for a 407-amino acid polypeptide whose structural analysis was consistent with an integral membrane glycoprotein. In particular, the extracellular domain was rich in serine and threonine residues at which carbohydrate substitution is likely through O- and N-linked glycosylation. This would explain the higher molecular weight of the antigen whose polypeptide backbone is approximately M(r) 42,000. Further computer-aided sequence analyses revealed no significant homology with any member of the CEA gene family. The cross-reactivity with anti-CEA monoclonal antibodies may be explained by the presence of CEA and normal cross-reacting antigen homologous sites proximal to the transmembrane region. No sequence homology was found with any known protein. Thus, the M(r) 110,000 molecule represents a potentially novel cell membrane glycoprotein whose possible role in human cancer and/or as a gamma-interferon-inducible gene product warrants further investigation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. KUMAMOTO UNIV,SCH MED,DEPT SURG 2,KUMAMOTO 860,JAPAN. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RI Takahashi, Masayuki/D-8079-2012 NR 22 TC 20 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1994 VL 54 IS 14 BP 3831 EP 3836 PG 6 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600033 PM 8033103 ER PT J AU GOZUKARA, EM PARRIS, CN WEBER, CA SALAZAR, EP SEIDMAN, MM WATKINS, JF PRAKASH, L KRAEMER, KH AF GOZUKARA, EM PARRIS, CN WEBER, CA SALAZAR, EP SEIDMAN, MM WATKINS, JF PRAKASH, L KRAEMER, KH TI THE HUMAN DNA-REPAIR GENE, ERCC2 (XPD), CORRECTS ULTRAVIOLET HYPERSENSITIVITY AND ULTRAVIOLET HYPERMUTABILITY OF A SHUTTLE VECTOR REPLICATED IN XERODERMA-PIGMENTOSUM GROUP-D CELLS SO CANCER RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION REPAIR; COMPLEMENTATION GROUP-D; SACCHAROMYCES-CEREVISIAE; POINT MUTATIONS; COCKAYNES-SYNDROME; VARIANT CELLS; GROUP-A; GROUP-C; PLASMID; HELICASE AB To determine the contribution of a human DNA repair gene, ERCC2 (XPD), to mutagenesis in human cells, two ERCC2 (XPD)-transformed xeroderma pigmentosum complementation group D (XPD) cell lines with increased UV survival compared to XP6BE(SV40), the original XPD line, were studied: D6BE-ER2-2 with slightly increased UV survival; and D6BE-ER2-9 with normal UV survival. ERCC2 (XPD) antibody-reactive protein levels were elevated 4.8-fold in D6BE-ER2-2 and 17.6-fold in D6BE-ER2-9 relative to XP6BE(SV40). DNA repair ability was assessed by measuring the ability of the cells to restore expression to UV-treated plasmids. Transfection of pRSVcat exposed to 1000 J/m(2) UV resulted in 0.3% chloramphenicol acetyltransferase activity in XP6BE(SV40) cells but 20-80% in D6BE-ER2-2, DGBE-ER2-9, and repair-proficient cells compared to untreated control plasmids. The UV hypersensitivity of the mutagenesis shuttle vector pSP189 in XP6BE(SV40) cells was partially corrected and the UV hypermutability and excess of G:C --> A:T mutations of pSP189 fell to the normal range in D6BE-ER2-2 and D6BE-ER2-9 cells. However, the frequency of plasmids recovered with multiple base substitution mutations was significantly reduced with XP6BE(SV40) cells and remained low in D6BE-ER2-2 and D6BE-ER2-9 cells, when compared with the normal fibroblasts. The human DNA excision repair gene, ERCC2 (XPD), substantially corrected the plasmid UV hypersensitivity and UV hypermutability of xeroderma pigmentosum complementation group D cells; however, the dose response relationship varied for different end points. C1 NCI, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. LAWRENCE LIVERMORE NATL LAB, BIOL & BIOTECHNOL RES PROGRAM, LIVERMORE, CA USA. OTSUKA PHARMACEUT CO LTD, ROCKVILLE, MD 20850 USA. UNIV ROCHESTER, SCH MED, DEPT BIOPHYS, ROCHESTER, NY 14642 USA. RI Prakash, Satya/C-6420-2013; Prakash, Louise/C-7891-2012 FU Intramural NIH HHS [Z01 BC004517-31] NR 44 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1994 VL 54 IS 14 BP 3837 EP 3844 PG 8 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600034 PM 8033104 ER PT J AU NICOTERA, TM PRIVALLE, C WANG, TC OSHIMURA, M BARRETT, JC AF NICOTERA, TM PRIVALLE, C WANG, TC OSHIMURA, M BARRETT, JC TI DIFFERENTIAL PROLIFERATIVE RESPONSES OF SYRIAN-HAMSTER EMBRYO FIBROBLASTS TO PARAQUAT-GENERATED SUPEROXIDE RADICALS DEPENDING ON TUMOR-SUPPRESSOR GENE-FUNCTION SO CANCER RESEARCH LA English DT Article ID LIPID-PEROXIDATION; OXIDATIVE STRESS; CU,ZN-SUPEROXIDE DISMUTASE; NEOPLASTIC TRANSFORMATION; GLUTATHIONE-PEROXIDASE; EPIDERMAL-CELLS; PROMOTION; MOUSE; INVITRO; INDUCTION AB Oxygen radicals have been widely implicated in neoplastic transformation; however, little is known regarding their mode of action. In an attempt to delineate potential mechanisms of action, an analysis of superoxide effects on cell growth was studied in normal and two nontumorigenic, immortal cell lines derived from normal Syrian hamster embryo (SHE) fibroblasts. The two immortal cell lines differed in their ability to suppress tumorigenicity of tumor cells in cell hybrids. One cell line suppressed tumorigenicity (sup(+)), while a second clone was unable to suppress tumorigenicity (sup(-)). Paraquat was used to generate superoxide through its capacity to be reduced by NAD(P)H and to generate superoxide radicals. The growth response of the various cell types was measured by colony-forming ability as well as by tritiated thymidine incorporation using autoradiography. At low paraquat concentrations (25 mu M), primary SHE cells and two sup(+) clones showed up to a 40% enhancement in colony formation, while two sup(-) clones showed no increase. Toxicity was observed at high doses, starting at approximately 100 mu M paraquat. Since oxygen radicals are also mutagenic, primary SHE cells were examined for chromosomal aberrations. Chromatid gaps and breaks were induced at all concentrations of paraquat used. Thus, superoxide not only causes cellular toxicity at high doses but at low doses enhances cell growth of certain cells (primary SHE cells and sup(+) cells) but not others (sup(-) cells). Therefore, differing responses of cells at different stages of neoplastic progression must be considered in understanding oxygen radical effects in growth control and carcinogenesis. C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. ROSWELL PK CANC INST,DEPT BIOPHYS,BUFFALO,NY 14263. DUKE UNIV,MED CTR,DEPT BIOCHEM,DURHAM,NC 27710. TOTTORI UNIV,SCH LIFE SCI,DEPT MOLEC & CELLULAR GENET,YONAGO,TOTTORI,JAPAN. NR 44 TC 40 Z9 40 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 JUL 15 PY 1994 VL 54 IS 14 BP 3884 EP 3888 PG 5 WC Oncology SC Oncology GA NV956 UT WOS:A1994NV95600041 PM 8033111 ER PT J AU JAKAB, G SZALLASI, A VONAGOSTON, D AF JAKAB, G SZALLASI, A VONAGOSTON, D TI THE CALCITONIN-GENE-RELATED PEPTIDE (CGRP) PHENOTYPE IS EXPRESSED EARLY AND UP-REGULATED BY RESINIFERATOXIN (RTX) IN MOUSE SENSORY NEURONS SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Note DE CALCITONIN GENE-RELATED PEPTIDE; ONTOGENY; DORSAL ROOT GANGLION; CAPSAICIN; RESINIFERATOXIN ID DORSAL-ROOT GANGLION; PRIMARY AFFERENT NEURONS; SUBSTANCE-P; GUINEA-PIG; CAPSAICIN; RAT; RELEASE; NEUROPEPTIDE; IMMUNOREACTIVITY; MODULATION AB Calcitonin gene-related peptide (CGRP) immunoreactivity was detected at day 2 in vitro (embryonic day 15) in developing mouse dorsal root ganglion (DRG) neurons in primary culture. During 2 weeks of culture the proportion of CGRP-immunoreactive (CGRP-IR) neurons remained around 65-70%, much higher than usually found in adult animals (45-50%). Treatment of cultures with the capsaicin analog resiniferatoxin (RTX; 0.3-30 nM) significantly augmented CGRP immunoreactivity per neuron at all ages investigated without increasing the number of CGRP-immunoreactive cells. The increased CGRP immunoreactivity was observed both in the axonal varicosities and in the perinuclear region of cell bodies. This RTX-induced increase in CGRP immunoreactivity was completely blocked by Ruthenium red (RR). Treatment with the non-esterified form of RTX (resiniferol 9,13,14 orthophenylacetate, ROPA) produced no increase. These results suggest that: (1) early expression of the CGRP phenotype is regulated in a cell-autonomous way in developing mouse DRG neurons in vitro; and (2) the RTX-induced increase in CGRP biosynthesis is most likely the result of activating the capsaicin/RTX receptor rather than directly activating the protein kinase C (PKC) pathway in vitro. The results may also reflect qualitative and quantitative differences in capsaicin/RTX sensitivity of sensory neurons between embryonal and adult ages. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NICHHD,LDN,BETHESDA,MD 20892. NR 31 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUL 15 PY 1994 VL 80 IS 1-2 BP 290 EP 294 DI 10.1016/0165-3806(94)90116-3 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA NW941 UT WOS:A1994NW94100035 ER PT J AU KITAYAMA, S DOHI, T UHL, GR AF KITAYAMA, S DOHI, T UHL, GR TI PHORBOL ESTERS ALTER FUNCTIONS OF THE EXPRESSED DOPAMINE TRANSPORTER SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE DOPAMINE TRANSPORTER; PROTEIN KINASE C; COCAINE ID COCAINE BINDING; CLONING; ACTIVATION; CELLS; CDNA AB Recent elucidation of the amino acid sequences of the neurotransmitter transporters reveals several consensus sequences for phosphorylation by kinases including protein kinase C. Protein kinase C activation did modulate the function of the rat dopamine transporter expressed in COS cells. Cell treatment with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) reduced the affinity of binding of the radiolabeled cocaine analog [H-3](-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)trop (WIN 35,428) without affecting its B-max. The uptake of [3H]dopamine was reduced by treatment with PMA in a staurosporine-sensitive manner. Kinetic analysis revealed that the inhibitory effect of PMA on [H-3]dopamine uptake was due to reduced uptake velocity and a small reduction of affinity for Na+, without changed affinity for dopamine. 1-Oleoyl-2-acetyl-sn-glycerol (GAG) mimicked these actions of PMA. These results demonstrate that activation of protein kinase C alters dopamine transporter functions in both ligand recognition and substrate translocation. These phosphorylation phenomena in vitro suggest the possibility that phosphorylation could modulate the activity of this important dopaminergic synaptic regulator under physiological conditions. C1 NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. HIROSHIMA UNIV,SCH DENT,DEPT PHARMACOL,HIROSHIMA,JAPAN. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 18 TC 110 Z9 110 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JUL 15 PY 1994 VL 268 IS 2 BP 115 EP 119 DI 10.1016/0922-4106(94)90180-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NY378 UT WOS:A1994NY37800001 PM 7957633 ER PT J AU KUMAR, S KINOSHITA, M NODA, M COPELAND, NG JENKINS, NA AF KUMAR, S KINOSHITA, M NODA, M COPELAND, NG JENKINS, NA TI INDUCTION OF APOPTOSIS BY THE MOUSE NEDD2 GENE, WHICH ENCODES A PROTEIN SIMILAR TO THE PRODUCT OF THE CAENORHABDITIS-ELEGANS CELL-DEATH GENE CED-3 AND THE MAMMALIAN IL-1-BETA-CONVERTING ENZYME SO GENES & DEVELOPMENT LA English DT Article DE PROGRAMMED CELL DEATH; DEVELOPMENT; ICE; CED-3; CYSTEINE PROTEASE ID INTERLEUKIN-1-BETA CONVERTING ENZYME; WILD-TYPE P53; NERVOUS-SYSTEM; C-ELEGANS; GROWTH-FACTOR; BCL-2; EXPRESSION; SELECTION; SURVIVAL; CLONING AB By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery. C1 JAPANESE FDN CANC RES,INST CANC,DEPT VIRAL ONCOL,TOSHIMA KU,TOKYO 170,JAPAN. KYOTO UNIV,FAC MED,DEPT MOLEC ONCOL,SAKYO KU,KYOTO 606,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Kumar, Sharad/0000-0001-7126-9814 FU NCI NIH HHS [N01-CO-74101] NR 60 TC 573 Z9 577 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 1994 VL 8 IS 14 BP 1613 EP 1626 DI 10.1101/gad.8.14.1613 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NY992 UT WOS:A1994NY99200001 PM 7958843 ER PT J AU GAO, YT MCLAUGHLIN, JK BLOT, WJ JI, BT BENICHOU, J DAI, Q FRAUMENI, JF AF GAO, YT MCLAUGHLIN, JK BLOT, WJ JI, BT BENICHOU, J DAI, Q FRAUMENI, JF TI RISK-FACTORS FOR ESOPHAGEAL CANCER IN SHANGHAI, CHINA .1. ROLE OF CIGARETTE-SMOKING AND ALCOHOL-DRINKING SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GASTRIC CARDIA; ATTRIBUTABLE RISK; ADENOCARCINOMA; SHANXI AB A population-based case-control study of esophageal cancer was conducted in urban Shanghai involving interviews with 902 cases and 1,552 controls. Risk of esophageal cancer was increased among tobacco smokers and alcohol drinkers. Odds ratios (OR) for smoking were 2.1 and 1.6 for men and women, respectively, and increased with number of cigarettes smoked per day, duration of smoking, number of pack-years and decreasing age at start of smoking. For men who were current alcohol drinkers OR was 1.4, with the excess risk primarily among heavy drinkers. Few women drank alcoholic beverages. The combined effect of heavy smoking and drinking among men was pronounced: OR was 12.0 for those who smoked more than 1 pack per day and drank more than 750 g of ethanol per week. The relation with smoking appeared stronger for cancers of the middle and lower thirds of the esophagus than for the upper third, while patterns of risk for squamous cell carcinoma and adenocarcinoma were similar. Heavy drinking affected all 3 subsites, with increased risks mainly limited to squamous cell carcinoma. Cigarette smoking and alcohol drinking combined accounted for almost 50% of all esophageal cancers among men in Shanghai; among women, 14% of cases were attributed to smoking. Our study confirms that smoking and drinking are important risk factors for esophageal cancer in China, thereby paralleling findings from developed countries. (C) 1994 Wiley-Liss, Inc. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NR 24 TC 138 Z9 147 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 15 PY 1994 VL 58 IS 2 BP 192 EP 196 DI 10.1002/ijc.2910580208 PG 5 WC Oncology SC Oncology GA NX625 UT WOS:A1994NX62500007 PM 8026880 ER PT J AU GAO, YT MCLAUGHLIN, JK GRIDLEY, G BLOT, WJ JI, BT DAI, Q FRAUMENI, JF AF GAO, YT MCLAUGHLIN, JK GRIDLEY, G BLOT, WJ JI, BT DAI, Q FRAUMENI, JF TI RISK-FACTORS FOR ESOPHAGEAL CANCER IN SHANGHAI, CHINA .2. ROLE OF DIET AND NUTRIENTS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; VEGETABLES; LINXIAN; FRUIT; SUPPLEMENTATION; LESIONS; MEN AB A population-based case-control study of esophageal cancer (902 cases, 1,552 controls) in Shanghai, China, investigated the etiologic role of diet. After adjustment for cigarette smoking, alcohol consumption and other risk factors, increasing consumption of fruits, dark orange vegetables and beef or mutton was associated with statistically significant decreasing trends in risk for esophageal cancer. In general, risks were about 40% lower among those in the upper vs. lower quartiles of intake of these foods. Fivefold increases in risk were observed among those who consumed burning hot soup or porridge, with smaller excesses for preserved vegetables, salty and deep fried foods. Nutrient analysis revealed that increased dietary intake of protein, carotene, vitamins C and E and riboflavin was associated with reduced esophageal cancer risk. Our findings support the notion that the reported temporal increases in the per capita consumption of fruits, vegetables and animal products contribute to the substantial reduction in the incidence of esophageal cancer in Shanghai, particularly since cigarette and alcohol use has not decreased. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NR 32 TC 82 Z9 87 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 15 PY 1994 VL 58 IS 2 BP 197 EP 202 DI 10.1002/ijc.2910580209 PG 6 WC Oncology SC Oncology GA NX625 UT WOS:A1994NX62500008 PM 8026881 ER PT J AU DASILVA, L HOWARD, OMZ RUI, H KIRKEN, RA FARRAR, WL AF DASILVA, L HOWARD, OMZ RUI, H KIRKEN, RA FARRAR, WL TI GROWTH SIGNALING AND JAK2 ASSOCIATION MEDIATED BY MEMBRANE-PROXIMAL CYTOPLASMIC REGIONS OF PROLACTIN RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ERYTHROPOIETIN RECEPTOR; HORMONE RECEPTOR; TYROSINE KINASE; MOLECULAR-CLONING; LYMPHOMA-CELLS; ACTIVATION; EVOLUTION; DOMAIN; IDENTIFICATION; SUPERFAMILY AB Prolactin (PRL) has recently been demonstrated to induce tyrosine phosphorylation and activation of the cytoplasmic tyrosine kinase JAK2 in PRL-dependent Nb2 lymphoma cells. The present study represents an initial effort to identify cytoplasmic regions of the PRL receptor (PRLR) that are critical to growth signal generation and JAK2 activation. Variably truncated rat PRLRs were stably expressed in the murine 32D cell line. PRL-induced proliferation was mediated by the full-length receptor and the mutant G328, which contains the membrane-proximal Homology Boxes 1 and 2 characteristic of hematopoietin receptors. In contrast, mutant receptors lacking either Box 2 or both Boxes 1 and 2 were not capable of transmitting a growth signal. The mitogenic capacity of the PRLR variants correlated with JAK2 association and activation, as well as with induction of mRNA levels for the growth related gene ornithine decarboxylase. We conclude that mitogenic competence of rat PRLRs resides within the first 94 amino acids of the cytoplasmic domain. The data suggest that Homology Box 1/Box 2 region is critical to JAK2 phosphorylation and association with the PRLR. These findings mill serve as a basis for more detailed molecular characterization of PRLR domains essential for JAK2 interaction and growth signal generation. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU FIC NIH HHS [5FO5 TWO4300-02] NR 29 TC 128 Z9 129 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1994 VL 269 IS 28 BP 18267 EP 18270 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW798 UT WOS:A1994NW79800003 PM 8034567 ER PT J AU CHEN, YP OTOOLE, TE SHIPLEY, T FORSYTH, J LAFLAMME, SE YAMADA, KM SHATTIL, SJ GINSBERG, MH AF CHEN, YP OTOOLE, TE SHIPLEY, T FORSYTH, J LAFLAMME, SE YAMADA, KM SHATTIL, SJ GINSBERG, MH TI INSIDE-OUT SIGNAL-TRANSDUCTION INHIBITED BY ISOLATED INTEGRIN CYTOPLASMIC DOMAINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GLYCOPROTEIN-IIB-IIIA; PLATELET GPIIB-IIIA; AFFINITY MODULATION; LIGAND-BINDING; CELL-ADHESION; RECEPTOR; FIBRONECTIN; ALPHA-IIB-BETA-3; SPECIFICITY; FIBRINOGEN AB The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular signals provoke changes in the integrin extracellular domain resulting in ''activation,'' as manifested by an increase in affinity. Interactions of integrin cytoplasmic domains with intracellular elements may mediate this ''inside-out signaling.'' Here we report that overexpression of chimeras of the cytoplasmic domain of integrin beta(3) or beta(1) subunits, joined to the extracellular and transmembrane domains of the Tac subunit of the interleukin-2 receptor, reduced integrin affinity. In contrast, chimeras containing the cytoplasmic domain of alpha(5) or alpha(IIb) or of beta(3) bearing a mutation that disrupts inside out signaling lacked inhibitory activity. These data suggest that limiting quantities of intracellular factors bind to integrin beta(3) and beta(1) cytoplasmic domains to modulate ligand binding affinity. Structural mimics of these domains may provide a novel means to alter cell adhesion. C1 Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. UNIV PENN, DEPT MED, PHILADELPHIA, PA 19104 USA. RI O'Toole, Timothy/I-4172-2013; OI Yamada, Kenneth/0000-0003-1512-6805 FU NHLBI NIH HHS [HL-40387, HL-28235, HL-48728] NR 31 TC 174 Z9 176 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1994 VL 269 IS 28 BP 18307 EP 18310 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW798 UT WOS:A1994NW79800013 PM 8034576 ER PT J AU REITER, Y BRINKMANN, U JUNG, SH LEE, BK KASPRZYK, PG KING, CR PASTAN, I AF REITER, Y BRINKMANN, U JUNG, SH LEE, BK KASPRZYK, PG KING, CR PASTAN, I TI IMPROVED BINDING AND ANTITUMOR-ACTIVITY OF A RECOMBINANT ANTI-ERBB2 IMMUNOTOXIN BY DISULFIDE STABILIZATION OF THE FV FRAGMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; PROTEINS; TOXINS; FORMS AB e23(dsFv)-PE38KDEL is a recombinant immunotoxin composed of the Pv region of anti-erbB2 monoclonal antibody e23 connected to a truncated form of Pseudomonas exotoxin (PE38KDEL), in which the inherently unstable Fv heterodimer (composed of V-H and V-L) is stabilized by a disulfide bond engineered between structurally conserved framework positions of V-H and V-L. We have now found that e23(dsFv)-PE38KDEL is considerably more cytotoxic to antigen-positive cell lines than the corresponding single-chain immunotoxin. The basis for the enhanced cytotoxic activity is that the e23 dsFv-immunotoxin binds to erbB2 with greater affinity than the single-chain counterpart. The dsFv-immunotoxin had 4-fold increased binding compared to the scFv and almost identical to the binding affinity of e23 Fab. e23(dsFv)-PE38KDEL was also considerably more stable at 37 degrees C than the single-chain immunotoxin. The therapeutic potential of the disulfide-stabilized immunotoxin was compared with its single-chain counterpart using two animal models of immunodeficient mice bearing subcutaneous tumor xenografts of human gastric tumor N87 cells or human A431 epidermoid carcinoma cells. The antitumor effect of e23(dsFv)-PE38KDEL was significantly better than that of the single-chain immunotoxin. e23(dsFv)-PE38KDEL caused complete regression of tumors at doses which caused no toxic effects in mice, whereas the single-chain immunotoxin did not cause complete regressions at the same doses. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. ONCOLOGIX INC,GAITHERSBURG,MD 20878. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 18 TC 86 Z9 89 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1994 VL 269 IS 28 BP 18327 EP 18331 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW798 UT WOS:A1994NW79800017 PM 7913461 ER PT J AU GOLDBERGER, BA CONE, EJ AF GOLDBERGER, BA CONE, EJ TI CONFIRMATORY TESTS FOR DRUGS IN THE WORKPLACE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review ID SOLID-PHASE EXTRACTION; GC MS CONFIRMATION; 11-NOR-DELTA-9-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; SIMULTANEOUS IDENTIFICATION; ION TRAP; DELTA-9-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; COCAINE METABOLITES; URINARY-EXCRETION; INTERNAL STANDARD; ROBOTIC METHOD AB The Mandatory Guidelines for Federal Workplace Drug Testing Programs require the use of gas chromatography-mass spectrometry (GC-MS) for the confirmation of presumptive positive urine specimens. This review focuses upon GC-MS methods developed specifically for forensic confirmation of amphetamine, methamphetamine, 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-acid), benzoylecgonine, morphine, codeine and phencyclidine in urine for purposes of workplace drug testing. In addition, current laboratory issues pertaining to each drug class are reviewed. Generally, drug assays utilized either liquid-liquid or solid-phase extraction methods, derivatization if necessary, and GC-MS detection operating in the selected ion monitoring mode or by full scan acquisition. C1 NIDA,ADDICT RES CTR,CHEM & DRUG METAB SECT,BALTIMORE,MD 21224. NR 54 TC 49 Z9 53 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 15 PY 1994 VL 674 IS 1-2 BP 73 EP 86 DI 10.1016/0021-9673(94)85218-9 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NZ413 UT WOS:A1994NZ41300006 PM 8075776 ER PT J AU ISSAQ, HJ AF ISSAQ, HJ TI 4TH ANNUAL FREDERICK CONFERENCE ON CAPILLARY ELECTROPHORESIS, FREDERICK, MD, USA, OCTOBER 19-20, 1993 - FOREWORD SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Editorial Material RP ISSAQ, HJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUL 15 PY 1994 VL 657 IS 2 BP 263 EP 263 DI 10.1016/0378-4347(94)00315-7 PG 1 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PA243 UT WOS:A1994PA24300001 ER PT J AU CHAN, KC ALVARADO, AB MCGUIRE, MT MUSCHIK, GM ISSAQ, HJ SNADER, KM AF CHAN, KC ALVARADO, AB MCGUIRE, MT MUSCHIK, GM ISSAQ, HJ SNADER, KM TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND MICELLAR ELECTROKINETIC CHROMATOGRAPHY OF TAXOL AND RELATED TAXANES FROM BARK AND NEEDLE EXTRACTS OF TAXUS SPECIES SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article; Proceedings Paper CT 4th Annual Frederick Conference on Capillary Electrophoresis CY OCT 19-20, 1993 CL FREDERICK, MD ID PHASE-II; BREVIFOLIA; SEPARATION; CEPHALOMANNINE; CANCER; DRUG AB High-performance liquid chromatography (HPLC) and micellar electrokinetic chromatography (MEKC) were applied for the separation of taxol, cephalomannine, and baccatin III in crude extracts from the needle and bark of Taxus species. The chromatogram of the bark extract was cleaner than that of the needle allowing a more reliable detection of taxol and cephalomannine in the bark extract. However, HPLC quantitation of taxol in the needle extract would be difficult due to coeluting taxinines. Nevertheless, this was not a problem in the MEKC experiment. In comparison to HPLC, MEKC offered baseline resolution of taxol from taxinines in the needle extract, less solvent waste, a smaller sample requirement, and the simultaneous detection of taxol, cephalomannine and baccatin III in a relatively simpler electrophoretic run. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,DCT,DTP,NAT PROD BRANCH,FREDERICK,MD 21702. NR 27 TC 24 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUL 15 PY 1994 VL 657 IS 2 BP 301 EP 306 DI 10.1016/S0378-4347(94)80006-5 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PA243 UT WOS:A1994PA24300006 PM 7952094 ER PT J AU JANINI, GM CHAN, KC MUSCHIK, GM ISSAQ, HJ AF JANINI, GM CHAN, KC MUSCHIK, GM ISSAQ, HJ TI ANALYSIS OF NITRATE AND NITRITE IN WATER AND URINE BY CAPILLARY ZONE ELECTROPHORESIS SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article; Proceedings Paper CT 4th Annual Frederick Conference on Capillary Electrophoresis CY OCT 19-20, 1993 CL FREDERICK, MD ID ION-CHROMATOGRAPHY; SEPARATION; ANIONS; CATIONS AB A capillary zone electrophoresis method for the separation and analysis of nitrate and nitrite in water and urine was developed. No interference in the electropherogram from other anions is observed by using a polyacrylamide-coated column with a modified phosphate buffer at pH 3 for the separation, and UV absorption at 214 nm for the detection. The method does not require sample pretreatment or the use of organic solvents. The limit of detection for each analyte (S/N = 3), using a 75 mu m I.D. capillary, is 0.5 mu g/ml. Urine samples require 40-fold dilution in order to maintain migration time reproducibility to within 1% relative standard deviation. RP JANINI, GM (reprint author), NCI, FREDERICK CANC RES & DEV CTR, DYNCORP, PROGRAM RESOURCES INC, POB B, FREDERICK, MD 21702 USA. NR 11 TC 44 Z9 44 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUL 15 PY 1994 VL 657 IS 2 BP 419 EP 423 DI 10.1016/0378-4347(94)00141-3 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PA243 UT WOS:A1994PA24300020 PM 7952107 ER PT J AU HERSHKOVIZ, R CAHALON, L MIRON, S ALON, R SAPIR, T AKIYAMA, SK YAMADA, KM LIDER, O AF HERSHKOVIZ, R CAHALON, L MIRON, S ALON, R SAPIR, T AKIYAMA, SK YAMADA, KM LIDER, O TI TNF-ALPHA ASSOCIATED WITH FIBRONECTIN ENHANCES PHORBOL-MYRISTATE ACETATE-MEDIATED OR ANTIGEN-MEDIATED INTEGRIN-DEPENDENT ADHESION OF CD4+ T-CELLS VIA PROTEIN-TYROSINE PHOSPHORYLATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXTRACELLULAR-MATRIX PROTEINS; FIBROBLAST GROWTH-FACTOR; HEPARIN-LIKE MOLECULES; SIGNAL TRANSDUCTION; LYMPHOCYTE-T; KINASE-C; RECEPTOR; BINDING AB The effects of cytokines on immune cells may be influenced by their milieu, such as the extracellular matrix (ECM), in the vicinities of which cytokines and inflammatory cells interact and function. Previously, we demonstrated that TNF-alpha bound to fibronectin (FN) and augments the level of adhesion of activated CD4(+) cells. Herein, we examined the mechanisms of this pro-adhesive activity of TNF-alpha and its putative physiologic consequences using human or rat CD4(+) cells. A brief exposure of CD4(+) cells to low dosages of soluble TNF-alpha or of FN- or laminin-bound TNF-alpha synergized with PMA to enhance the integrin-mediated binding of CD4(+) cells to these immobilized ECM moieties. TNF-alpha-enhanced adhesion of CD4(+) cells did not delay or inhibit the subsequent detachment of the cells from the substrate, and adhesion was increased provided the cells were treated with TNF-alpha immediately after their exposure to PMA. Th is indicates that the enhancing effect of TNF-alpha requires a previous activation of the cells. When TNF-alpha was immobilized on FN, less TNF-alpha was required to induce CD4(+) cell binding to FN. Soluble, and to a greater extent FN-bound, TNF-alpha synergizes with PMA to intensify protein tyrosine phosphorylation in FN-bound CD4(+) cells, and this effect of TNF-alpha was inhibited by inhibitors of tyrosine kinase. That FN-bound or soluble TNF-alpha also amplified the binding of an Ag-specific autoimmune rat T cell line to immobilized FN, emphasizes the physiologic relevance of our findings. Thus, the signal transduction and cell adhesive properties of ECM glycoproteins may be modulated upon their association with TNF-alpha, and matrix-linked TNF-alpha may recruit and direct immune cells to inflammatory sites. C1 WEIZMANN INST SCI,DEPT CELL BIOL,IL-76100 REHOVOT,ISRAEL. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 48 TC 39 Z9 40 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 554 EP 565 PG 12 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300009 PM 7517419 ER PT J AU BEHRENS, TW JAGADEESH, J SCHERLE, P KEARNS, G YEWDELL, J STAUDT, LM AF BEHRENS, TW JAGADEESH, J SCHERLE, P KEARNS, G YEWDELL, J STAUDT, LM TI JAW1, A LYMPHOID-RESTRICTED MEMBRANE-PROTEIN LOCALIZED TO THE ENDOPLASMIC-RETICULUM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VESICULAR TRANSPORT; GOLGI TRANSPORT; MESSENGER-RNAS; CELL; EXPRESSION; YEAST; ER; RECEPTOR; TISSUE; GENE AB Jaw1 is a novel lymphoid-restricted gene that is expressed in a developmentally regulated fashion in both the B and T cell lineages. Jaw1 mRNA is abundantly expressed in pre-B and B cell lines with minimal or undetectable expression in plasma cell lines. Pre-T cell lines and normal mouse thymocytes express high levels of Jaw1 mRNA, whereas most mature T cell lines express low levels. Comparison of the mouse and human genes reveals that Jaw1 encodes a 539 amino acid protein with a highly conserved coiled-coil domain in the middle third of the protein and a COOH-terminal transmembrane domain. Jaw1 was localized to the endoplasmic reticulum (ER) of lymphocytes by indirect immunofluorescence and confocal microscopy. When overexpressed in Hela cells, Jaw1 protein targeted to the ER. In vitro translation of Jaw1 in the presence of canine microsomes demonstrated that Jaw1 is an integral membrane protein of the ER and is oriented on the ER membrane facing the cytosol. Jaw1 is a member of a class of proteins with COOH-terminal hydrophobic membrane anchors and is structurally similar to proteins involved in vesicle targeting and fusion. These findings suggest that the function and/or the structure of the ER in lymphocytes may be modified by lymphoid-restricted resident ER proteins. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT MED RHEUMATOL,MINNEAPOLIS,MN 55455. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 43 TC 38 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 682 EP 690 PG 9 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300022 PM 8021504 ER PT J AU NEURATH, MF STROBER, W WAKATSUKI, Y AF NEURATH, MF STROBER, W WAKATSUKI, Y TI THE MURINE IG 3'ALPHA ENHANCER IS A TARGET SITE WITH REPRESSOR FUNCTION FOR THE B-CELL LINEAGE-SPECIFIC TRANSCRIPTION FACTOR BSAP (NF-HB, S-ALPHA-BP) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN ENHANCER; DNA-BINDING PROTEIN; NUCLEAR FACTOR; IMMUNOGLOBULIN ENHANCER; GENE-EXPRESSION; SWITCH REGIONS; 3' ENHANCER; KAPPA-B; DIFFERENTIATION; PROMOTER AB Using electrophoretic mobility shift assays (EMSAs) we have identified several target sites for nuclear proteins in the murine heavy chain Ig 3'alpha enhancer. Two of these sites, denoted oligo-H and oligo-K, were shown by several criteria, including cell distribution and stimulation experiments, EMSA cross-competition studies, and proteolytic clipping bandshift assays, to bind to the same protein identical to the transcription factor B cell lineage-specific activator protein (BSAP) (NF-HB, S alpha-BP). To assess the possible functional role of these BSAP binding sites in the 3'alpha enhancer, we transiently transfected a construct containing a 314-bp 3'alpha enhancer fragment upstream of a luciferase reporter gene in MOPC-315 cells, a plasmacytoma line lacking BSAP. In these cells, co-transfection with a vector expressing recombinant BSAP led to significant reduction in the activity of the 3'alpha enhancer fragment. Conversely, in the mature B lymphoma cell line CH12.LX, a cell line that expresses BSAP and has a less active 3'alpha enhancer, selective BSAP down-regulation by an antisense phosphorothioate oligonucleotide was sufficient to considerably up-regulate 3'alpha enhancer activity, as were mutations of both binding sites that prevented binding of BSAP to the 3'alpha enhancer. Our findings thus suggest that the natural loss of BSAP expression in terminally differentiated plasma cells contributes to the activation of the murine Ig 3'alpha enhancer. RP NEURATH, MF (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N244-250,BETHESDA,MD 20892, USA. NR 55 TC 94 Z9 94 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 730 EP 742 PG 13 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300027 PM 8021508 ER PT J AU CHEEVER, AW WILLIAMS, ME WYNN, TA FINKELMAN, FD SEDER, RA COX, TM HIENY, S CASPAR, P SHER, A AF CHEEVER, AW WILLIAMS, ME WYNN, TA FINKELMAN, FD SEDER, RA COX, TM HIENY, S CASPAR, P SHER, A TI ANTI-IL-4 TREATMENT OF SCHISTOSOMA-MANSONI-INFECTED MICE INHIBITS DEVELOPMENT OF T-CELLS AND NON-B, NON-T CELLS EXPRESSING TH2 CYTOKINES WHILE DECREASING EGG-INDUCED HEPATIC-FIBROSIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE SCHISTOSOMIASIS; GRANULOMA-FORMATION; CD4+ LYMPHOCYTES; DOWN-REGULATION; GOAT ANTIBODY; MOUSE IGD; IL-4; INTERLEUKIN-4; EOSINOPHILIA; INDUCTION AB Increasing evidence suggests that schistosome egg granulomas are primarily Th2 cellular reactions. Mice infected with Schistosoma mansoni were treated with a neutralizing mAb against IL-4 to evaluate the role of this cytokine in the generation of parasite egg-induced cell-mediated responses and hepatic pathology. Animals treated with anti-IL-4 before egg deposition showed decreased IL-4, IL-5, and IL-10 production in response to in vitro antigenic stimulations and decreased IL-5 and IL-13 mRNA levels in the liver. As observed previously, non-B, non-T cells were a major source of IL-4 in infected mice treated with control mAb, and the diminished IL-4 response in anti-IL-4-treated animals was shown to be caused at least in part by a reduction in the number of these cells, as well as by decreased secretion of IL-4 per cell. In contrast, production of the Th1 cytokines IL-2 and IFN-gamma was elevated in anti-IL-4-treated infected mice in vitro, and the corresponding mRNAs in the liver were increased. Anti-IL-4 treatment did not consistently reduce the size of hepatic granulomas around S. mansoni eggs, but markedly inhibited granuloma formation in the lungs of the same animals after i.v. egg injection. Nevertheless, anti-IL-4-treated infected mice showed consistent and marked reductions in hepatic collagen deposition. These findings indicate that IL-4 plays a major role in the development of the Th2 response in S. mansoni-infected mice and contributes to the pathogenesis of hepatic fibrosis. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MED,BETHESDA,MD 20892. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 27 TC 213 Z9 222 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 753 EP 759 PG 7 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300029 PM 8021510 ER PT J AU SARIN, A CLERICI, M BLATT, SP HENDRIX, CW SHEARER, GM HENKART, PA AF SARIN, A CLERICI, M BLATT, SP HENDRIX, CW SHEARER, GM HENKART, PA TI INHIBITION OF ACTIVATION-INDUCED PROGRAMMED CELL-DEATH AND RESTORATION OF DEFECTIVE IMMUNE-RESPONSES OF HIV+ DONORS BY CYSTEINE PROTEASE INHIBITORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MATURE T-CELLS; MARROW TRANSPLANTATION; MONONUCLEAR-CELLS; INFECTED PATIENTS; LYMPHOCYTES-T; APOPTOSIS; AIDS; CD4; INDIVIDUALS AB In vitro activation of PBLs from HIV+ individuals resulted in programmed cell death (PCD) within 2 days in 58 of 95 HIV+ blood donors, in contrast to only two of 30 control HIV- donors. CD4(+) and CD8(+) T cells from HIV+ donors died under these conditions, and these cells showed apoptotic nuclear morphology and DNA fragmentation. To test the hypothesis that this cell death shares a common biochemical pathway with that induced by TCR cross-linking in normal dividing T cells, inhibitors of the calcium-activated cysteine protease calpain were tested for their ability to block the activation-induced PCD of HIV+ donors. The E-64 (epoxysuccinyl) class of cysteine protease inhibitors gave 40% to 60% inhibition of HIV+ PCD responses, while the aldehyde inhibitors, leupeptin and calpain inhibitor II, gave 60% to 67% inhibition. The involvement of this calpain-dependent death pathway in HIV-induced functional T helper cell deficiency was tested by examining the effect of calpain inhibitors on the defective Ag- and mitogen-dependent proliferative responses of HIV+ donors. Twenty to fifty percent of such defective responses were significantly restored toward normal levels by calpain inhibitors, whereas control responses by normal donors were largely unaffected. These data suggest that a calpain-dependent PCD pathway contributes to HIV-associated immunodeficiency and suggest the use of calpain inhibitors as a possible route to therapy of HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 35 TC 110 Z9 112 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 862 EP 872 PG 11 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300042 PM 8021517 ER PT J AU SINGER, DS KOHN, LD ZINGER, H MOZES, E AF SINGER, DS KOHN, LD ZINGER, H MOZES, E TI METHIMAZOLE PREVENTS INDUCTION OF EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS IN MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTI-DNA IDIOTYPE; ANTIBODIES AB Experimental SLE can be induced in mice by immunization with a human mAb to DNA (16/6ld). Immunized mice develop Abs to the 16/6ld immunogen, DNA, and nuclear Ags. Subsequently, clinical manifestations of disease develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. MHC class I Ags play a critical role in the induction of experimental SLE, as demonstrated by the finding that class I-deficient mice are resistant to disease induction. This finding suggested that agents that reduce MHC class I expression might mitigate experimental SLE in normal mice. These studies report that methimazole, which has:been shown to repress class I transcription in some cell lines, reduces class I expression on PBLs in vivo and prevents the development of clinical manifestations of SLE in 16/6ld-immunized mice. These data suggest that methimazole, which has been used in the treatment of Graves' disease, may be useful in the clinical treatment of SLE and other autoimmune diseases. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP SINGER, DS (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 48 Z9 48 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1994 VL 153 IS 2 BP 873 EP 880 PG 8 WC Immunology SC Immunology GA NW183 UT WOS:A1994NW18300043 PM 8021518 ER PT J AU CLORE, GM OMICHINSKI, JG SAKAGUCHI, K ZAMBRANO, N SAKAMOTO, H APPELLA, E GRONENBORN, AM AF CLORE, GM OMICHINSKI, JG SAKAGUCHI, K ZAMBRANO, N SAKAMOTO, H APPELLA, E GRONENBORN, AM TI HIGH-RESOLUTION STRUCTURE OF THE OLIGOMERIZATION DOMAIN OF P53 BY MULTIDIMENSIONAL NMR SO SCIENCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ISOTOPICALLY ENRICHED PROTEINS; RESTRAINED MOLECULAR-DYNAMICS; MULTIPLE QUANTUM COHERENCE; DNA-BINDING; DISTANCE GEOMETRY; 3-DIMENSIONAL STRUCTURE; J COUPLINGS; PEPTIDE COMPLEX; LARGER PROTEINS AB The three-dimensional structure of the oligomerization domain (residues 319 to 360) of the tumor suppressor p53 has been solved by multidimensional heteronuclear magnetic resonance (NMR) spectroscopy. The domain forms a 20-kilodalton symmetric tetramer with a topology made up from a dimer of dimers. The two primary dimers each comprise two antiparallel helices linked by an antiparallel beta sheet. One beta strand and one helix are contributed from each monomer. The interface between the two dimers forming the tetramer is mediated solely by helix-helix contacts. The overall result is a symmetric, four-helix bundle with adjacent helices oriented antiparallel to each other and with the two antiparallel beta sheets located on opposing faces of the molecule. The tetramer is stabilized not only by hydrophobic interactions within the protein core but also by a number of electrostatic interactions. The implications of the structure of the tetramer for the biological function of p53 are discussed. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008; Sakamoto, Hiroshi/A-3181-2011; Zambrano, Nicola/B-9352-2014 OI Clore, G. Marius/0000-0003-3809-1027; Zambrano, Nicola/0000-0001-9395-3481 NR 69 TC 277 Z9 280 U1 2 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 15 PY 1994 VL 265 IS 5170 BP 386 EP 391 DI 10.1126/science.8023159 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NW816 UT WOS:A1994NW81600038 PM 8023159 ER PT J AU SPEIR, E MODALI, R HUANG, ES LEON, MB SHAWL, F FINKEL, T EPSTEIN, SE AF SPEIR, E MODALI, R HUANG, ES LEON, MB SHAWL, F FINKEL, T EPSTEIN, SE TI POTENTIAL ROLE OF HUMAN CYTOMEGALOVIRUS AND P53 INTERACTION IN CORONARY RESTENOSIS SO SCIENCE LA English DT Article ID CELLULAR TUMOR-ANTIGEN; SV40-TRANSFORMED CELLS; TRANSFORMED-CELLS; NUCLEAR ANTIGEN; PROTEIN; VIRUS; EXPRESSION; CARCINOMA; PROLIFERATION; ANTIBODY AB A subset of patients who have undergone coronary angioplasty develop restenosis, a vessel renarrowing characterized by excessive proliferation of smooth muscle cells (SMCs). Of 60 human restenosis lesions examined, 23 (38 percent) were found to have accumulated high amounts of the tumor suppressor protein p53, and this correlated with the presence of human cytomegalovirus (HCMV) in the lesions. SMCs grown from the lesions expressed HCMV protein IE84 and high amounts of p53. HCMV infection of cultured SMCs enhanced p53 accumulation, which correlated temporally with IE84 expression. IE84 also bound to p53 and abolished its ability to transcriptionally activate a reporter gene. Thus, HCMV, and IE84-mediated inhibition of p53 function, may contribute to the development of restenosis. C1 BIOSERVE BIOTECHNOL LTD,LAUREL,MD 20707. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. WASHINGTON HOSP CTR,WASHINGTON CARDIOL CTR,DIV CARDIOL,WASHINGTON,DC 20010. WASHINGTON ADVENTIST HOSP,DEPT CARDIOL,TAKOMA PK,MD 20912. RP SPEIR, E (reprint author), NIH,CARDIOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 32 TC 627 Z9 639 U1 1 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 15 PY 1994 VL 265 IS 5170 BP 391 EP 394 DI 10.1126/science.8023160 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NW816 UT WOS:A1994NW81600039 PM 8023160 ER PT J AU PARMAR, MKB SPIEGELHALTER, DJ FREEDMAN, LS AF PARMAR, MKB SPIEGELHALTER, DJ FREEDMAN, LS TI THE CHART TRIALS - BAYESIAN DESIGN AND MONITORING IN PRACTICE SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL ID CLINICAL-TRIAL; RADIOTHERAPY AB In this paper we describe the design and monitoring of two large randomized trials being conducted through the British Medical Research Council (MRC) Cancer Trials Office. In particular we discuss the issues involved in the design of the trials, specifying the null and alternative hypotheses and how the design has influenced the monitoring procedure used. From these two examples, and some other MRC experiences, we suggest some basic considerations which could be applied to many MRC and other trials. C1 UNIV CAMBRIDGE,MRC,INST PUBL HLTH,BIOSTAT UNIT,CAMBRIDGE CB2 2SR,ENGLAND. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. RP PARMAR, MKB (reprint author), MRC,CANC TRIALS OFF,5 SHAFTESBURY RD,CAMBRIDGE CB2 2BW,ENGLAND. OI Morgan, David/0000-0002-2291-1740 NR 17 TC 70 Z9 70 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1297 EP 1312 DI 10.1002/sim.4780131304 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800002 PM 7973211 ER PT J AU GELLER, NL AF GELLER, NL TI INTERIM ANALYSIS - THE ALPHA-SPENDING APPROACH - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion ID SEQUENTIAL CLINICAL-TRIALS; DESIGN RP GELLER, NL (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1353 EP 1356 DI 10.1002/sim.4780131309 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800007 ER PT J AU FREEDMAN, LS SPIEGELHALTER, DJ PARMAR, MKB AF FREEDMAN, LS SPIEGELHALTER, DJ PARMAR, MKB TI THE WHAT, WHY AND HOW OF BAYESIAN CLINICAL-TRIALS MONITORING SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL ID INTERIM ANALYSES AB We discuss the advantages and limitations of group sequential methods for monitoring clinical trials data. We describe a Bayesian approach, based upon the use of sceptical prior distributions, that avoids some of the limitations of group sequential methods. We illustrate its use with data from a trial of levamisole plus 5-Fluorouracil for colorectal cancer. C1 ADDENBROOKES HOSP,MRC,INST PUBL HLTH,BIOSTAT UNIT,CAMBRIDGE CB2,ENGLAND. MCR,CANC TRIALS OFF,CAMBRIDGE CB2 2BB,ENGLAND. RP FREEDMAN, LS (reprint author), NIH,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,ROOM 344,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 16 TC 49 Z9 49 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1371 EP 1383 DI 10.1002/sim.4780131312 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800010 PM 7973217 ER PT J AU SIMON, R AF SIMON, R TI SOME PRACTICAL ASPECTS OF THE INTERIM MONITORING OF CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL ID CANCER; BIAS AB The decision to stop accrual early to a clinical trial is often difficult and multifaceted. Interim monitoring boundaries have been found useful in U.S. oncology trials for such decisions for reasons described here. This paper also discusses rationale that lead to more conservative approaches to early stopping decisions than are currently employed. A recent initiative of the National Cancer Institute to achieve the objectives of independent data monitoring committees in the phase III clinical trials which it sponsors is also described. RP SIMON, R (reprint author), NCI,BIOMET RES BRANCH,6130 EXECUT BLVD,ROOM 739,ROCKVILLE,MD 20852, USA. NR 14 TC 22 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1401 EP 1409 DI 10.1002/sim.4780131315 PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800013 PM 7973219 ER PT J AU HARRINGTON, D CROWLEY, J GEORGE, SL PAJAK, T REDMOND, C WIEAND, S AF HARRINGTON, D CROWLEY, J GEORGE, SL PAJAK, T REDMOND, C WIEAND, S TI THE CASE AGAINST INDEPENDENT MONITORING COMMITTEES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL C1 FRED HUTCHINSON CANC RES CTR,BETHESDA CTR,SW ONCOL GRP,CTR STAT,SEATTLE,WA 98104. DUKE UNIV,MED CTR,CALGB,CTR STAT,DURHAM,NC 27710. UNIV PITTSBURGH,NSABP,CTR STAT,PITTSBURGH,PA 15261. MAYO CLIN & MAYO FDN,N CENT CANC TREATMENT GRP,CTR STAT,ROCHESTER,MN 55905. RP HARRINGTON, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR CIVIL ENGN,EASTERN COOPERAT ONCOL GRP,BOSTON,MA 02115, USA. NR 4 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1411 EP 1414 DI 10.1002/sim.4780131316 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800014 PM 7973220 ER PT J AU PROSCHAN, MA FOLLMANN, DA GELLER, NL AF PROSCHAN, MA FOLLMANN, DA GELLER, NL TI MONITORING MULTIARMED TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL ID CLINICAL-TRIALS AB We propose and discuss several methods of monitoring multi-armed trials comparing means or survival. These methods combine multiple comparison procedures such as Fisher's LSD, Newman-Keuls and Tukey's with monitoring boundaries such as those of O'Brien and Fleming and Lan and DeMets. Tables of boundaries are provided for the equal variance or equal censoring distribution case. RP PROSCHAN, MA (reprint author), NHLBI,7550 WISCONSIN AVE,FED BLDG,ROOM 2A11,BETHESDA,MD 20892, USA. NR 14 TC 20 Z9 20 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1441 EP 1452 DI 10.1002/sim.4780131320 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800018 PM 7973223 ER PT J AU GREEN, SB FREEDMAN, LS AF GREEN, SB FREEDMAN, LS TI EARLY STOPPING OF PREVENTION TRIALS WHEN MULTIPLE OUTCOMES ARE OF INTEREST - A DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion ID CLINICAL-TRIALS; ENDPOINTS; DESIGNS AB In large prevention and screening trials, we want to answer multiple questions simultaneously. When monitoring prevention trials with multiple disease outcomes, composite measures may be useful, such as a count of important events, or a comparison of expected mortality. There are advantages to investigating multiple interventions in the same prevention or screening trial, using all-versus-none, factorial, or reciprocal control designs. In these situations it may be important to answer some questions early while others are still being investigated. RP GREEN, SB (reprint author), NCI,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1479 EP 1484 DI 10.1002/sim.4780131325 PG 6 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800023 PM 7973227 ER PT J AU GRASBERGER, BL CLORE, GM GRONENBORN, AM AF GRASBERGER, BL CLORE, GM GRONENBORN, AM TI HIGH-RESOLUTION STRUCTURE OF ASCARIS TRYPSIN-INHIBITOR IN SOLUTION - DIRECT EVIDENCE FOR A PH-INDUCED CONFORMATIONAL TRANSITION IN THE REACTIVE-SITE SO STRUCTURE LA English DT Article DE ASCARIS TRYPSIN INHIBITOR; NMR SPECTROSCOPY; PH-DEPENDENT CONFORMATIONAL TRANSITION; SOLUTION STRUCTURE ID NUCLEAR-MAGNETIC-RESONANCE; STREPTOMYCES SUBTILISIN INHIBITOR; RESTRAINED MOLECULAR-DYNAMICS; DISTANCE GEOMETRY; 3-DIMENSIONAL STRUCTURE; CHYMOTRYPSIN ELASTASE; STEREOSPECIFIC ASSIGNMENTS; PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; ISOINHIBITORS AB Background: The Ascaris trypsin inhibitor (ATI) is a member of a new family of serine protease inhibitors isolated from the helminthic worm Ascaris lumbricoides var suum. This family comprises five chymotrypsin/elastase inhibitors and one trypsin inhibitor. Members are characterized by the presence of five disulfide bonds (two of which are located on either side of the reactive site) in a single small protein domain of 61-62 residues. Results: The solution structure of ATI has been determined at pH 2.4 and pH 4.75 by NMR spectroscopy. Iterative refinement permitted the unambiguous assignment of the pairing of the five disulfide bridges (Cys5-Cys38, Cys15-Cys33, Cys18-Cys29, Cys22-Cys60, and Cys40-Cys54) which were previously unknown. The structure includes four short beta-strands arranged in two approximately perpendicular beta-sheets. The reactive site loop is bounded by two disulfide bridges (Cys15-Cys33 and Cys18-cys29) and is part of the long loop (residues 15-25) connecting strands beta1 and beta2. Comparison of the nuclear Overhauser enhancement data at the two pH values revealed significant differences centered around the reactive site. While the reactive site at pH 2.4 closely resembles that of other protease inhibitors, at pH 4.75 the reactive site loop undergoes a major conformational rearrangement involving the psi backbone torsion angles of the P2, P1 and P1' residues (residues 30-32). This is associated with a change in the positions of the side chains of Arg31 and Glu32. Conclusions: The overall three-dimensional structure of ATI posesses an unusual fold and, with the exception of the reactive site, shows no similarity to other serine protease inhibitors. The observation that the reactive site of the low pH form of ATI is similar to that of other serine proteases suggests that this is the active form of the protein. C1 NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 46 TC 55 Z9 57 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JUL 15 PY 1994 VL 2 IS 7 BP 669 EP 678 DI 10.1016/S0969-2126(00)00067-8 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NZ802 UT WOS:A1994NZ80200011 PM 7922043 ER PT J AU JOHNSTON, JA KAWAMURA, M KIRKEN, RA CHEN, YQ BLAKE, TB SHIBUYA, K ORTALDO, JR MCVICAR, DW O'SHEA, JJ AF JOHNSTON, JA KAWAMURA, M KIRKEN, RA CHEN, YQ BLAKE, TB SHIBUYA, K ORTALDO, JR MCVICAR, DW O'SHEA, JJ TI PHOSPHORYLATION AND ACTIVATION OF THE JAK-3 JANUS KINASE IN RESPONSE TO INTERLEUKIN-2 SO NATURE LA English DT Article ID PROTEIN-TYROSINE KINASE; GAMMA SIGNAL-TRANSDUCTION; RECEPTOR-BETA; INTERFERON-ALPHA/BETA; IL-2; SUBUNIT; CHAIN; PATHWAY AB LUTERLEUKIN-2 is an autocrine growth factor for T cells(1,2) which also activates other cells including B cells(3) and natural killer cells(4). The subunits of the interleukin-2 receptor (IL-2R) lack intrinsic enzymatic activity, but protein tyrosine phosphorylation is a critical event following ligand binding and src family kinases, such as Lck, are known to be activated by IL-2 (refs 5-9). However, IL-2 signalling can occur in the absence of receptor interaction with Lck, suggesting that other protein tyrosine kinases might be important(10). Here we report that a new member of the Janus family of kinases (Jak-3) is coupled to the IL-2R in human peripheral blood T cells and natural killer cells. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, ADV BIOSCI LABS INC, FREDERICK, MD 21702 USA. RP JOHNSTON, JA (reprint author), NCI, FREDERICK CANC RES & DEV CTR, EXPTL IMMUNOL LAB, LEUKOCYTE CELL BIOL SECT, FREDERICK, MD 21702 USA. RI McVicar, Daniel/G-1970-2015 NR 28 TC 512 Z9 516 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 14 PY 1994 VL 370 IS 6485 BP 151 EP 153 DI 10.1038/370151a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NW804 UT WOS:A1994NW80400060 PM 8022485 ER PT J AU BENOWITZ, NL HENNINGFIELD, JE AF BENOWITZ, NL HENNINGFIELD, JE TI ESTABLISHING A NICOTINE THRESHOLD FOR ADDICTION - THE IMPLICATIONS FOR TOBACCO REGULATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CIGARETTE-SMOKING; CARBON-MONOXIDE; TAR; YIELDS; EXPOSURE; BIOAVAILABILITY; SMOKERS C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110. NATL INST DRUG ABUSE,BALTIMORE,MD 21224. FU NIDA NIH HHS [DA01696, DA02277] NR 21 TC 241 Z9 243 U1 2 U2 19 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 1994 VL 331 IS 2 BP 123 EP 125 DI 10.1056/NEJM199407143310212 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NW712 UT WOS:A1994NW71200012 PM 7818638 ER PT J AU CHILCOAT, HD AF CHILCOAT, HD TI THE WAR ON DRUGS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP CHILCOAT, HD (reprint author), NIH,BALTIMORE,MD 21224, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 1994 VL 331 IS 2 BP 126 EP 126 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NW712 UT WOS:A1994NW71200013 PM 8208255 ER PT J AU COLAIANNI, LA AF COLAIANNI, LA TI PEER-REVIEW IN JOURNALS INDEXED IN INDEX-MEDICUS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 2nd International Congress on Peer Review in Biomedical Publication CY SEP 09-11, 1993 CL AMER MED ASSOC, CHICAGO, IL HO AMER MED ASSOC AB Objective.-To determine whether peer review policies are published in English-language journals indexed in Index Medicus and, secondarily, to obtain information on the peer review practices of such journals. Design.-Examined one issue of a sample of all journal titles written in English and indexed in Index Medicus, and all indexed English-language journals in four subject fields. A questionnaire was sent to the editors of journals in the subject fields requesting information on their peer review practices. Setting.-Journals received at the National Library of Medicine. Participants.-Editors of journals in four subject fields. Main Outcome Measure.-Existence of a printed statement of the peer review process for manuscripts. Results.-Although the editors queried in the four subject fields indicated that overall, 56% to 65% of the articles were peer reviewed, clear statements about their peer review practices were not found in half of their journals or in the overall sample. Conclusions.-Editors should publish clear statements of the peer review process followed for each type of article published in their journals. RP COLAIANNI, LA (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 2 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 13 PY 1994 VL 272 IS 2 BP 156 EP 158 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NV424 UT WOS:A1994NV42400022 PM 8015132 ER PT J AU SAFAR, J ROLLER, PP GAJDUSEK, DC GIBBS, CJ AF SAFAR, J ROLLER, PP GAJDUSEK, DC GIBBS, CJ TI SCRAPIE AMYLOID (PRION) PROTEIN HAS THE CONFORMATIONAL CHARACTERISTICS OF AN AGGREGATED MOLTEN GLOBULE FOLDING INTERMEDIATE SO BIOCHEMISTRY LA English DT Article ID ALPHA-LACTALBUMIN; CIRCULAR-DICHROISM; STATE; BINDING; FORM; STABILITY; APOMYOGLOBIN; INFECTIVITY; TRANSITIONS; CONVERSION AB The scrapie amyloid (prion) protein (PrP27-30) is a host-derived component of the infectious scrapie agent; the potential to replicate, propagate, and form amyloid is a result of the posttranslational event or conformational abnormality. In low concentrations of guanidine hydrochloride (Gdn.HCl), PrP27-30 dissociates into a compact equilibrium intermediate with a substantial portion of secondary structure, partially denatured tertiary structure, and tryptophan residues in an apolar environment [Safar, J., Roller, P. P., Gajdusek, D. C., and Gibbs, C. J., Jr. (1993) J. Biol. Chem. 27, 20276-20284]. Here we describe the characteristics of this metastable form as monitored by 8-anilino-1-naphthalenesulfonate (ANS) fluorescence spectroscopy and circular dichroism (CD) spectroscopy, and we propose a mechanism for scrapie amyloid association. The Gdn.HCl-induced equilibrium intermediate of PrP27-30 had multiple high-affinity hydrophobic binding sites for ANS, some close to the Trp residues. The amide CD spectrum of an acid-induced intermediate (A-form), in equilibrium at pH <2.0, was similar to the Gdn. HCl-induced intermediate and suggested the presence of a significant portion of an alpha-helical or beta-turn secondary structure. In contrast, the PrP27-30 associated into aggregates in an all-beta-sheet conformation with less ordered and more exposed hydrophobic side chains. The noncooperative unfolding of the Gdn.HCl-induced intermediate at high temperature was irreversible and correlated with the loss of infectivity. The results demonstrate that PrP27-30 associates through a compact, metastable hydrophobic intermediate with a nonnative, nondenatured secondary structure and a tertiary structure close to the unfolded form. The molten globule-like characteristics suggest that the scrapie amyloid (prion) protein is an aggregated form of an equilibrium intermediate or an early kinetic intermediate of PrP folding pathways. C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. RP SAFAR, J (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,BLDG 36,ROOM 4A-15,BETHESDA,MD 20892, USA. RI Safar, Jiri/G-6512-2013 NR 55 TC 101 Z9 102 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 12 PY 1994 VL 33 IS 27 BP 8375 EP 8383 DI 10.1021/bi00193a027 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NX329 UT WOS:A1994NX32900027 PM 8031772 ER PT J AU YASAR, S SCHINDLER, CW THORNDIKE, EB GOLDBERG, SR AF YASAR, S SCHINDLER, CW THORNDIKE, EB GOLDBERG, SR TI EVALUATION OF DEPRENYL FOR COCAINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS IN RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DEPRENYL; COCAINE; DRUG DISCRIMINATION ID AMPHETAMINE; METABOLITES; PHENYLETHYLAMINE; METHAMPHETAMINE; (-)-DEPRENYL; (-)DEPRENYL; SELEGILINE; INHIBITION; BRAIN AB The antiparkinsonian agent l-deprenyl is metabolized to l-methamphetamine and l-amphetamine and, at higher doses, can facilitate the release and inhibit the reuptake of dopamine. Since l-deprenyl can affect dopamine release and reuptake it was important to evaluate it for cocaine-like discriminative stimulus effects. Male Fisher rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline in a two-lever, operant-conditioning procedure using schedules of food-delivery or stimulus-shock termination. l-Deprenyl (17 mg/kg, i.p.) produced full generalization to cocaine under the food-delivery schedule but this or higher doses produced only partial generalization to cocaine under the stimulus-shock termination schedule. d-Deprenyl produced full generalization to cocaine under both schedules at i.p. doses of 5.6 to 10 mg/kg. These cocaine-like discriminative stimulus effects occur only at doses that are well above the clinically relevant dose range for l-deprenyl. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. RP YASAR, S (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 11 PY 1994 VL 259 IS 3 BP 243 EP 250 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NW912 UT WOS:A1994NW91200004 PM 7982450 ER PT J AU KOONIN, EV AF KOONIN, EV TI PREDICTION OF AN RIBOSOMAL-RNA METHYLTRANSFERASE DOMAIN IN HUMAN TUMOR-SPECIFIC NUCLEOLAR PROTEIN P120 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSION; SEQUENCE; DNA; RNA; INHIBITION; 2'-O-METHYLTRANSFERASE; PROLIFERATION; GROWTH; CELLS; GENE AB Using computer methods for identification of amino acid motifs in sequence databases and multiple alignment, it is shown that human proliferation-associated nucleolar protein P120 contains a putative methyltransferase domain that is conserved in a group of bacterial proteins. It is hypothesized that P120 and the related prokaryotic proteins are rRNA methylases required for division of all types of cells. RP KOONIN, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 24 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1994 VL 22 IS 13 BP 2476 EP 2478 DI 10.1093/nar/22.13.2476 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NZ215 UT WOS:A1994NZ21500006 PM 8041608 ER PT J AU SAX, CM CVEKL, A KANTOROW, M SOMMER, B CHEPELINSKY, AB PIATIGORSKY, J AF SAX, CM CVEKL, A KANTOROW, M SOMMER, B CHEPELINSKY, AB PIATIGORSKY, J TI IDENTIFICATION OF NEGATIVE-ACTING AND PROTEIN-BINDING ELEMENTS IN THE MOUSE ALPHA-A-CRYSTALLIN -1556/-1165-REGION SO GENE LA English DT Article DE RECOMBINANT DNA; CHICKEN; GENE EXPRESSION; TRANSCRIPTION; EYE LENS; REPRESSOR; REPETITIVE ELEMENT ID LENS EPITHELIAL-CELLS; VIMENTIN GENE-EXPRESSION; CHLORAMPHENICOL ACETYLTRANSFERASE; REGULATORY ELEMENT; PROMOTER ELEMENTS; NUCLEAR PROTEINS; MAMMALIAN-CELLS; SEQUENCE MOTIF; TRANSCRIPTION; DNA AB The mouse alpha A-crystallin-encoding gene (alpha A-cry) is expressed in a highly lens-preferred manner. To date, it has been shown that this lens-preferred expression is controlled by four proximal positive-acting transcriptional regulatory elements: DE1 (-111/-97), alpha A-CRYBP1 (-66/-57), PE1/TATA (-35/-19) and PE2 (+24/+43). The present study extends our knowledge of mouse alpha A-cry transcriptional regulatory elements to the far upstream region of that gene by demonstrating that the -1556 to -1165 region contains negative-acting sequence elements which function in transfected lens cells derived from mouse, rabbit and chicken. This is the first negative-acting regulatory region identified in mouse alpha A-cry. The -1556 to -1165 region contains sequences similar to repressor/silencer elements identified in other genes, including those highly expressed in the lens, such as the delta 1-crystallin (delta 1-cry) and vimentin (vim) genes. The -1480 to -1401 region specifically interacts with nuclear proteins isolated from the alpha TN4-1 mouse lens cell line. Contained within this protein-binding region and positioned at -1453 to -1444 is a sequence (RS1) similar to the chicken delta 1-cry intron 3 repressor, and which competes for the formation of -1480 to -1401 DNA-protein complexes. Our findings suggest that lens nuclear proteins bind to the mouse alpha A-cry RS1 region. We demonstrate that the chicken delta 1-cry intron repressor binds similar nuclear proteins in chicken embryonic lens cells and mouse alpha TN4-1 lens cells. However, the mouse alpha A-cry RS1 region does not appear to bind the same protein(s) that bind to the chicken delta 1-cry intron repressor, suggesting the existence of a family of silencer proteins that recognize a similar site in the diverse cry genes. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. RI Cvekl, Ales/B-2427-2013 NR 50 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 8 PY 1994 VL 144 IS 2 BP 163 EP 169 DI 10.1016/0378-1119(94)90374-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NX653 UT WOS:A1994NX65300002 PM 8039701 ER PT J AU MOSCOW, JA HE, R GUDAS, JM COWAN, KH AF MOSCOW, JA HE, R GUDAS, JM COWAN, KH TI UTILIZATION OF MULTIPLE POLYADENYLATION SIGNALS IN THE HUMAN RHOA PROTOONCOGENE SO GENE LA English DT Article DE GLUTATHIONE PEROXIDASE 1; LUNG CANCER; COLON CANCER; LOVASTATIN ID GLUTATHIONE-S-TRANSFERASE; GENE FAMILY; ADP-RIBOSYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; LUNG-CANCER; EXPRESSION; CELLS; LOVASTATIN; REDUCTASE; PROTEINS AB Little is known regarding the regulation of expression of the RHOA protooncogene, a member of the family of genes encoding Ras-related GTP-binding proteins. We have previously reported that the 3' untranslated region (UTR) of RHOA was contained within a genomic sequence which flanked the 5' end of the human glutathione peroxidase 1-encoding gene [J.A. Moscow et al., J. Biol. Chem. 267 (1992) 5949-5958]. Our previous studies revealed the presence of multiple (1.8 and 1.5 kb) RHOA mRNA species in breast cancer cell lines and of three putative polyadenylation signals in the RHOA 3' UTR. In this report, we have isolated several RHOA cDNAs from a multidrug-resistant MCF-7 human breast cancer cell line. Sequence analyses of these RHOA cDNA clones indicate that multiple polyadenylation signals are used to terminate RHOA transcripts. RNase-protection analysis demonstrated that all three polyadenylation signals are utilized in breast cancer cell lines and RNA stability studies demonstrated that RHOA RNA species with different 3' ends have equivalent stability. Since little is known about the RNA expression of RHOA in human tumors, and since both activated and non-activated RHOA gene possess transformation potential, we analyzed RHOA mRNA in lung and colon tumors by Northern blot and RNase-protection analyses. In all eight lung tumors examined, RHOA RNA levels were decreased relative to the level in normal surrounding tissue, whereas RHOA expression was decreased in only two of six colon tumors. We also found that lovastatin-induced cell cycle arrest resulted in increased RHOA RNA expression in breast cancer cell lines. RNase-protection analysis of RHOA RNA from these tumor and cell line specimens demonstrated that the relative abundance of RNA transcripts utilizing these three polyadenylation signals did not vary with total RHOA mRNA levels. RP MOSCOW, JA (reprint author), NCI,MED & PEDIAT BRANCHE,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 30 TC 15 Z9 16 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 8 PY 1994 VL 144 IS 2 BP 229 EP 236 DI 10.1016/0378-1119(94)90382-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA NX653 UT WOS:A1994NX65300010 PM 8039707 ER PT J AU FLEISCHER, B XIE, JP MAYRLEITNER, M SHEARS, SB PALMER, DJ FLEISCHER, S AF FLEISCHER, B XIE, JP MAYRLEITNER, M SHEARS, SB PALMER, DJ FLEISCHER, S TI GOLGI COATOMER BINDS, AND FORMS K+-SELECTIVE CHANNELS GATED BY, INOSITOL POLYPHOSPHATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLATHRIN ASSEMBLY PROTEIN; PLANAR LIPID BILAYERS; COATED VESICLES; ION CHANNELS; RECEPTOR; PURIFICATION; TRANSPORT; MEMBRANES; COMPLEX; PHOSPHATES AB Coatomer is a distinct type of coat protein complex involved in the formation of specific Golgi intercisternal transport vesicles. Direct binding studies using purified coatomer isolated from bovine liver cytosol show that coatomer specifically binds both inositol 1,3,4,5-tetrakisphosphate ((1,3,4,5)IP4) and inositol hexakisphosphate (IP6) with subnanomolar affinities (0,1 and 0.2 nM, respectively). Diphosphoinositol pentakisphosphate (PP-IP5) is an efficient competitor for both (1,3,4,5)IP4 and IF, binding to coatomer, Inositol 1,3,4,5,6-pentakisphosphate ((1,3,4,5,6)IP,) is a poor inhibitor of IF, binding, whereas little or no competition is detected with inositol 1,4,5-trisphosphate ((1,4,5)I-P-3). Coatomer displays ion channel activity when reconstituted into planar bilayers which is preferentially permeable to K+. Permeability ratios of the channel are P-K+/P-Cl- similar to 8.0 and PK+/P-N(a+) similar to 7.1, indicating a cation-selective channel with selectivity of K+ over Na+. In symmetrical 500 mM KCl, the smallest observable unitary channel conductance is 8.3 picosiemens. The coatomer channel activity is normally active with long open times (0.1 to several seconds) and is selectively blocked by 10 mu M (1,3,4,5)IP4, 1 mu M IP6, and 0.27 mu M PP-IP5; even lower concentrations are sufficient to induce channel flicker. The channel activity is not affected by (1,4,5)IP3, or (1,3,4,5,6)IP5. Thus, the channel activity of coatomer is modulated by the inositol polyphosphates which exhibit tight binding to the complex. C1 VANDERBILT UNIV, DEPT MOLEC BIOL, NASHVILLE, TN 37235 USA. NIEHS, CELLULAR & MOLEC PHARMACOL LAB, INOSITOL LIPID SECT, RES TRIANGLE PK, NC 27709 USA. SLOAN KETTERING INST, ROCKEFELLER RES LAB, PROGRAM CELLULAR BIOCHEM & BIOPHYS, NEW YORK, NY 10021 USA. FU NHLBI NIH HHS [HL32711] NR 33 TC 80 Z9 80 U1 0 U2 2 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 JUL 8 PY 1994 VL 269 IS 27 BP 17826 EP 17832 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200014 PM 8027036 ER PT J AU JIMENEZCERVANTES, C SOLANO, F KOBAYASHI, T URABE, K HEARING, VJ LOZANO, JA GARCIABORRON, JC AF JIMENEZCERVANTES, C SOLANO, F KOBAYASHI, T URABE, K HEARING, VJ LOZANO, JA GARCIABORRON, JC TI A NEW ENZYMATIC FUNCTION IN THE MELANOGENIC PATHWAY - THE 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID OXIDASE ACTIVITY OF TYROSINASE-RELATED PROTEIN-1 (TRP1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE MELANOMA-CELLS; PERFORMANCE LIQUID-CHROMATOGRAPHY; DOPACHROME TAUTOMERASE; MAMMALIAN TYROSINASE; METAL-IONS; EUMELANIN; GENE; CDNA; MELANOCYTES; CONVERSION AB Since the characterization of 5,6 dihydroxyindole-2-carboxylic acid (DHICA) as a major melanogenic intermediate, the fate of this compound and the mechanisms of its incorporation into the melanin polymer have become major issues in the study of melanogenesis. DHICA is a stable dihydroxyindole with a low rate of spontaneous oxidation, suggesting that enzymatic mechanism(s) might contribute to its evolution. The most obvious candidates are the melanosomal tyrosinases. We have recently shown that mouse melanosomes contain two electrophoretically distinct tyrosinase isoenzymes, termed low electrophoretic mobility tyrosinase (LEMT) and high electrophoretic mobility tyrosinase (HEMT), that can be resolved and purified. In this study, we report immunological evidence indicating that LEMT corresponds to the protein encoded by the brown locus (termed tyrosinase-related protein-1, TRP1), while HEMT corresponds to the tyrosinase encoded by the albino locus. We have compared the ability of both isoenzymes to catalyze DHICA evolution as determined by high performance liquid chromatography; although LEMT is a relatively poor tyrosine hydroxylase and DOPA oxidase as compared to HEMT, it was readily able to accelerate DHICA consumption concomitant with the production of a brownish product. However, the DHICA conversion activity of HEMT was barely detectable. The ability of purified LEMT to catalyze DHICA conversion could be almost completely abolished by treatment with heat or trypsin, and was inhibited in a concentration dependent way by the tyrosinase inhibitor 2-phenylthiourea and by L-tyrosine, Moreover, in the presence of low concentration of ascorbate, the DHICA conversion activity of LEMT displayed a lag period which was progressively longer at higher ascorbate concentrations. Based on the relationship between ascorbate added, enzyme activity, and lag period, it is very likely that the DHICA converting activity is indeed a DHICA oxidase activity. This was further proven by the demonstration that the product reacts rapidly and efficiently with the quinone trapping reagent 3-methyl-2-benzothiazolinone hydrazone, yielding a colored adduct similar to the one obtained with DOPAquinone. The DHICA oxidase activity of LEMT displayed a K-m for DHICA of about 0.8 mM, as compared to 1.9 mM for L-DOPA and 0.23 mM for L tyrosine. These results suggest that TRP1, the product of the brown locus, is indeed a tyrosinase with DHICA oxidase activity. However, as opposed to the tyrosinase encoded by the albino locus, TRP1's role in melanogenesis could be more directly related to DHICA metabolism than to the first steps of the pathway. C1 UNIV MURCIA,FAC MED,DEPT BIOCHEM & MOLEC BIOL,MURCIA,SPAIN. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Jimenez-Cervantes, Celia/H-1953-2015; Garcia-Borron, Jose Carlos/H-2247-2015; Solano, Francisco/G-5001-2013 OI Jimenez-Cervantes, Celia/0000-0002-5821-9510; Garcia-Borron, Jose Carlos/0000-0002-9192-588X; Solano, Francisco/0000-0001-9612-761X NR 50 TC 187 Z9 193 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 1994 VL 269 IS 27 BP 17993 EP 18000 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200039 PM 8027058 ER PT J AU OLAH, ME JACOBSON, KA STILES, GL AF OLAH, ME JACOBSON, KA STILES, GL TI IDENTIFICATION OF AN ADENOSINE RECEPTOR DOMAIN SPECIFICALLY INVOLVED IN BINDING OF 5'-SUBSTITUTED ADENOSINE AGONISTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MOLECULAR-CLONING; A1; ANTAGONISTS; EXPRESSION; AFFINITY; SITE AB The bovine A(1) adenosine receptor (A(1)AR) and rat A(3) adenosine receptor (A(3)AR) display distinct agonist and antagonist binding properties. To identify regions involved in ligand recognition, A(1)AR/A(3)AR chimeric receptors were created, expressed in COS-7 cells, and analyzed by radioligand binding. A chimeric receptor in which the third intracellular loop of the A(1)AR was replaced with that of the A(3)AR bound agonists and the antagonist, [H-3]xanthine amine congener, with affinities identical to wild-type A(1)AR. A chimeric receptor with the fifth transmembrane domain (TM5) and third intracellular loop of the A(1)AR replaced with that of the A(3)AR displayed antagonist affinity similar to wild-type A(1)AR. However, relative to the A(1)AR, this chimeric demonstrated much greater affinity for 5'-substituted analogs, whereas affinity for N-6-substituted compounds was unaffected. Substitution of a 6-amino acid cassette of the exofacial half of TM5 of the A(3)AR into the A(1)AR produced enhanced binding of exclusively a 5'-substituted analog, indicating involvement of this specific region in ligand recognition. These findings suggest that the 5'- and N-6-substituents of adenosine agonists bind to distinct regions of ARs and that TM5 of the A(3)AR interacts more favorably with 5'-substituted compounds than does that of the A(1)AR. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. NIDDK,MOLEC RECOGNIT SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [P50HL17670, R01HL35134] NR 28 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 1994 VL 269 IS 27 BP 18016 EP 18020 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200042 PM 8027060 ER PT J AU CHIRON, MF FRYLING, CM FITZGERALD, DJ AF CHIRON, MF FRYLING, CM FITZGERALD, DJ TI CLEAVAGE OF PSEUDOMONAS-EXOTOXIN AND DIPHTHERIA-TOXIN BY A FURIN-LIKE ENZYME PREPARED FROM BEEF-LIVER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBTILISIN FAMILY; KEX2-LIKE ENDOPROTEASE; PROTECTIVE ANTIGEN; CELLULAR PROTEASE; MEDIATED CLEAVAGE; FRAGMENT; CYTOSOL; SITE; EXPRESSION; ACTIVATION AB Pseudomonas exotoxin (PE) is cleaved within mammalian cells between Arg(279) and Gly(280) to generate an enzymatically active COOH terminal fragment of 37 kDa which translocates to the cytosol and ADP-ribosylates elongation factor 2. A protease, with toxin cleaving activity, was prepared from beef liver and subsequently characterized. After achieving a 500-fold enrichment in several chromatographic steps, a soluble form of this protease was identified as a furin-like enzyme. It cleaved PE on the COOH-terminal side of the sequence of RQPR (amino acids 276-279) producing the same fragments as those generated within cells. Cleavage had a pH optimum of 5.0-5.5, was inhibited by EDTA or p-hydroxymercuribenzoate but not by O-phenanthroline, N-ethylmaleimide, trans-epoxysuccinyl-L-leucylamido-(4-guanidino)-butane, or PMSF (or other well known inhibitors of serine proteases). The beef protease cleaved PE with an apparent K-m of 7 mu M. A mutant form of PE, PEala281, was cleaved at the same site, with the same pH optimum, a similar K-m (9 mu M) but with a V-max 150 times faster than was seen with the native toxin. Mutational analysis of the amino acids located just before the site of cleavage, confirmed the importance of arginines at P-1 and P-4. It was also noted that the introduction of a dibasic pair at 278-279 did not increase toxicity or appreciably improve the rate of cleavage. Unnicked diphtheria toxin (DT) was also cleaved by the beef protease; cleavage was on the COOH terminal side of the sequence RVRR (amino acids 190-193), was seen at pH values ranging from 5.5 to 8.5 and had an optimum at pH 8.0. Recombinant furin cleaved PE, PEala281, and DT with the same characteristics as the beef protease. In addition, Western blot analysis revealed that anti-furin antibodies reacted specifically with components in the beef protease preparation. Immunodepletion experiments showed that all toxin-cleavage activity could be removed from the beef protease using anti-furin anti-bodies. The relevance of furin-mediated cleavage was further assessed by adding nicked toxins to intact cells. Nicked PE and DT both killed cells at a faster rate than their unnicked counterparts. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-12197]; NCRR NIH HHS [RR-04869] NR 37 TC 99 Z9 101 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 1994 VL 269 IS 27 BP 18167 EP 18176 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200062 PM 8027078 ER PT J AU THOMPSON, MW MAURIZI, MR AF THOMPSON, MW MAURIZI, MR TI ACTIVITY AND SPECIFICITY OF ESCHERICHIA-COLI CLPAP PROTEASE IN CLEAVING MODEL PEPTIDE-SUBSTRATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT PROTEASE; MULTICATALYTIC PROTEINASE; ACTIVATED ATPASE; PROTEOLYSIS; COMPONENT; LA; DEGRADATION; SEQUENCE; CELLS; TI AB Escherichia coli ClpAP protease is an ATP-dependent protease composed of the proteolytic component ClpP and a regulatory ATPase, ClpA. ClpAP protease degraded a variety of peptide bonds in protein and peptide substrates at a slow rate (k(cat) less than or equal to 30 min(-1)/subunit of ClpP), but showed very high activity (k(cat) greater than or equal to 800 min(-1)) for a synthetic peptide composed of the first 19 amino acids of ClpP, MSYSGERDNFAPHMALVPV, referred to as the propeptide. The propeptide was not degraded by ClpP alone, but was degraded in the presence of ClpA and ClpP. Degradation was activated by nonhydrolyzable analogs of ATP, indicating that nucleotide-promoted interaction between ClpA and ClpP is sufficient to activate ClpP for propeptide cleavage. The propeptide, as well as truncated forms lacking either the first 9 or the last 3 amino acids, was cleaved at the same Met-Ala bond at which autoprocessing occurs in vivo. No hydrolysis of FAPHMALVPV derivatives was observed when Met was replaced by Glu, Lys, Ser, Tyr, Ile, and D-Met, but cleavage at the same position did occur with Leu or Trp substitutions. A peptide composed of a tandem repeat of FAPHMALVPV was cleaved between both Met-Ala bonds (k(cat) values greater than or equal to 39 min(-1)). Propeptides inhibited degradation of alpha-casein by competition for a binding site on ClpA, and they stimulated the basal ATPase activity of ClpA in the absence of ClpP. Peptides and protein substrates interact at an allosteric site on ClpA, which appears to be the site at which specific substrates are recognized by the Clp protease. RP THOMPSON, MW (reprint author), NCI, CELL BIOL LAB, BLDG 37, RM 1B07, BETHESDA, MD 20892 USA. NR 36 TC 109 Z9 110 U1 1 U2 2 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 JUL 8 PY 1994 VL 269 IS 27 BP 18201 EP 18208 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200066 PM 8027081 ER PT J AU THOMPSON, MW SINGH, SK MAURIZI, MR AF THOMPSON, MW SINGH, SK MAURIZI, MR TI PROCESSIVE DEGRADATION OF PROTEINS BY THE ATP-DEPENDENT CLP PROTEASE FROM ESCHERICHIA-COLI - REQUIREMENT FOR THE MULTIPLE ARRAY OF ACTIVE-SITES IN CLPP BUT NOT ATP HYDROLYSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE PROTEASES; LA; COMPONENT; PROTEOLYSIS; BREAKDOWN; COMPLEX; TI; UBIQUITIN; MECHANISM; SEQUENCE AB ClpP, the proteolytic component of the ATP-dependent ClpAP protease, is composed of 12 identical subunits and has intrinsic degradative activity against short peptides. Degradation of proteins and some peptides by ClpP requires the regulatory component ClpA and ATP. Peptide and protein substrates have been used to distinguish the roles of nucleotide binding and nucleotide hydrolysis in the activation of ClpAP protease. ATP binding alone promoted interaction between ClpA and ClpP, affected the substrate response curves for very short peptides, and activated degradation of larger peptides that were not degraded by ClpP alone. ATP hydrolysis did not increase in proportion to the increase in peptide bond hydrolysis of short peptides. However, ATP hydrolysis was strictly required for degradation of proteins such as alpha-casein; there was no indication of even limited cleavage of protein substrates when nonhydrolyzable analogs of ATP were used. Most large peptides and proteins were degraded in multiple sites without release of high molecular weight intermediates. Partial inactivation of ClpP with diisopropyl fluorophosphate produced ClpP with one to three active subunits/dodecamer. When only a few active sites were available in the active complex of ClpAP, degradation of large peptides and proteins released significant amounts of high molecular weight intermediates. Thus, processive degradation of protein substrates is a function of the multiple array of proteolytic active sites within the ClpP dodecamer. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 24 TC 129 Z9 130 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 1994 VL 269 IS 27 BP 18209 EP 18215 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200067 PM 8027082 ER PT J AU CALDERON, SN ROTHMAN, RB PORRECA, F FLIPPENANDERSON, JL MCNUTT, RW XU, H SMITH, LE BILSKY, EJ DAVIS, P RICE, KC AF CALDERON, SN ROTHMAN, RB PORRECA, F FLIPPENANDERSON, JL MCNUTT, RW XU, H SMITH, LE BILSKY, EJ DAVIS, P RICE, KC TI PROBES FOR NARCOTIC RECEPTOR-MEDIATED PHENOMENA .19. SYNTHESIS OF (+)-4-[(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBENZYL]-N,N-DIETHYLBENZAMIDE (SNC-80) - A HIGHLY SELECTIVE, NONPEPTIDE DELTA-OPIOID RECEPTOR AGONIST SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID NCX BINDING-SITES; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; OPIATE RECEPTOR; RAT-BRAIN; BW373U86; CLONING; SUBTYPES; PEPTIDES; ANTAGONISTS C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. USN,RES LAB,STRUCT MATTER LAB,CODE 6030,WASHINGTON,DC 20375. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. BURROUGHS WELLCOME CO,DIV ORGAN CHEM,RES TRIANGLE PK,NC 27709. NR 43 TC 174 Z9 174 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 8 PY 1994 VL 37 IS 14 BP 2125 EP 2128 DI 10.1021/jm00040a002 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NW321 UT WOS:A1994NW32100002 PM 8035418 ER PT J AU ACTON, EM NARAYANAN, VL RISBOOD, PA SHOEMAKER, RH VISTICA, DT BOYD, MR AF ACTON, EM NARAYANAN, VL RISBOOD, PA SHOEMAKER, RH VISTICA, DT BOYD, MR TI ANTICANCER SPECIFICITY OF SOME ELLIPTICINIUM SALTS AGAINST HUMAN BRAIN-TUMORS IN-VITRO SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CELL-LINES; DRUG SCREEN; PHASE-II AB Novel structure-activity relationships (SAR) distinct from known SAR for ellipticines have been revealed for certain ellipticinium salts. In particular, ellipticiniums such as the prototypical 9-methoxy-2-methylellipticinium (I- or OAc-) were found to be preferentially cytotoxic to the brain tumor cell line subpanel of the NCI 60 cell-line screening panel. Similar specificity also was apparent with 9-unsubstituted ellipticiniums, or others bearing 9-methyl or 9-chloro substituents. In contrast, 9-hydroxy-substituted ellipticiniums, as well as all nonquaternized ellipticines tested, were devoid of brain tumor specificity. Therefore, it did not appear that this unusual preference was correlated with the relative availability of redox cycling mechanisms, since redox cycling presumably is blocked in 9-methyl- and 9-chloroellipticiniums. Indeed, related investigations have indicated that the brain tumor specificity is mediated by preferential uptake and intracellular accumulation of the specific ellipticiniums. The present study further supports that the NCI in vitro ''disease-oriented'' primary screen can facilitate the discovery of novel, selectively cytotoxic leads for in vivo and mechanistic investigations. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG SYNTHESIS & CHEM BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-87231] NR 28 TC 83 Z9 85 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 8 PY 1994 VL 37 IS 14 BP 2185 EP 2189 DI 10.1021/jm00040a010 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NW321 UT WOS:A1994NW32100010 PM 8035425 ER PT J AU JURAYJ, J HAUGWITZ, RD VARMA, RK PAULL, KD BARRETT, JF CUSHMAN, M AF JURAYJ, J HAUGWITZ, RD VARMA, RK PAULL, KD BARRETT, JF CUSHMAN, M TI DESIGN AND SYNTHESIS OF ELLIPTICINIUM SALTS AND 1,2-DIHYDROELLIPTICINES WITH HIGH SELECTIVITIES AGAINST HUMAN CNS CANCERS IN-VITRO SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA TOPOISOMERASE-II; TUMOR-CELL-LINES; CLEAVAGE; AGENTS; DRUGS; CYCLODEXTRIN; DERIVATIVES; SERIES AB 9-Methoxy-2-methylellipticinium acetate (6), along with the 9-methyl and 9-chloro derivatives (7, and 8, respectively) have shown remarkable selectivities in vitro against the NCI human CNS cancer subpanel. In order to target these types of compounds to the CNS in vivo, a series of 1,2-dihydroellipticines was synthesized. 9-Methoxy-2-methyl-1,2-dihydroellipticine (9) retained the potency and selectivity of the parent compound 6 but was unstable toward oxidation to 6. In order to improve the stability of 9, it was converted to the vinylogous amide 33 by introduction of a formyl group in the 4-position. Compound 33 proved to be much more stable than 9, but it was also less potent than 9 by about 1 order of magnitude, and it was less selective for the CNS subpanel than 9. To overcome the limited water solubilities of the ellipticines and dihydroellipticines, several ellipticine analogues incorporating polar groups on the N-2 nitrogen were prepared. The 2-(methoxymethyl)ellipticinium salts 24 and 25, as well as the (methylthio)methyl congener 26, were relatively potent anticancer agents which displayed cytotoxicity selectivity profiles similar to compound 6. The cytotoxic dihydroellipticines 9 and 10 exhibited potencies approaching that of ellipticine itself in facilitating the formation of a ''cleavable complex'', while the least cytotoxic ellipticine derivatives exhibited no cleavage above background. C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NCI,DIV CANC TREATMENT,DRUG SYNTHESIS & CHEM BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. RW JOHNSON PHARMACEUT RES INST,DEPT MICROBIOL DISCOVERY,RARITAN,NJ 08869. FU NCI NIH HHS [N01-CM-17512] NR 37 TC 23 Z9 23 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 8 PY 1994 VL 37 IS 14 BP 2190 EP 2197 DI 10.1021/jm00040a011 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NW321 UT WOS:A1994NW32100011 PM 8035426 ER PT J AU MAGUIRE, J SANTORO, T JENSEN, P SIEBENLIST, U YEWDELL, J KELLY, K AF MAGUIRE, J SANTORO, T JENSEN, P SIEBENLIST, U YEWDELL, J KELLY, K TI GEM - AN INDUCED, IMMEDIATE-EARLY PROTEIN BELONGING TO THE RAS FAMILY SO SCIENCE LA English DT Article ID MECHANISM; GROWTH; ACTIVATION; CLONES; CELLS AB A gene encoding a 35-kilodalton guanosine triphosphate (GTP)-binding protein, Gem, was cloned from mitogen-induced human peripheral blood T cells. Gem and Rad, the product of a gene overexpressed in skeletal muscle in individuals with Type II diabetes, constitute a new family of Ras-related GTP-binding proteins. The distinct structural features of this family include the G3 GTP-binding motif, extensive amino- and carboxyl-terminal extensions beyond the Ras-related domain, and a motif that determines membrane association. Gem was transiently expressed in human peripheral blood T cells in response to mitogenic stimulation; the protein was phosphorylated on tyrosine residues and localized to the cytosolic face of the plasma membrane. Deregulated Gem expression prevented proliferation of normal and transformed 3T3 cells. These results suggest that Gem is a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 20 TC 148 Z9 151 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 8 PY 1994 VL 265 IS 5169 BP 241 EP 244 DI 10.1126/science.7912851 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV957 UT WOS:A1994NV95700039 PM 7912851 ER PT J AU GRAZIOSI, C PANTALEO, G GANTT, KR FORTIN, JP DEMAREST, JF COHEN, OJ SEKALY, RP FAUCI, AS AF GRAZIOSI, C PANTALEO, G GANTT, KR FORTIN, JP DEMAREST, JF COHEN, OJ SEKALY, RP FAUCI, AS TI LACK OF EVIDENCE FOR THE DICHOTOMY OF T(H)1 AND T(H)2 PREDOMINANCE IN HIV-INFECTED INDIVIDUALS SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL CLONES; INTERFERON-GAMMA PRODUCTION; MESSENGER-RNA EXPRESSION; CYTOKINE PRODUCTION; IFN-GAMMA; HELPER CELL; SCHISTOSOMA-MANSONI; GENE-EXPRESSION; HOMOSEXUAL MEN AB A switch from a T helper 1 (T(H)1) cytokine phenotype to a T(H)2 phenotype has been proposed as a critical element in the progression of human immunodeficiency virus (HIV) disease. Here, constitutive cytokine expression was analyzed in unfractionated and sorted cell populations isolated from peripheral blood and lymph nodes of HIV-infected individuals at different stages of disease. Expression of interleukin-2 (IL-2) and IL-4 was barely detectable (or undetectable) regardless of the stage of disease. CD8(+) cells expressed large amounts of interferon gamma and IL-10, and the levels of these cytokines remained stably high throughout the course of infection. Furthermore, similar patterns of cytokine expression were observed after stimulation in vitro of purified CD4(+) T cell populations obtained from HIV-infected individuals at different stages of disease. These results indicate that a switch from the T(H)1 to the T(H)2 cytokine phenotype does not occur during the progression of HIV disease. C1 INST RECH CLIN MONTREAL,IMMUNOL LAB,MONTREAL H2W 1R7,PQ,CANADA. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL H3C 3J7,PQ,CANADA. MCGILL UNIV,DEPT MICROBIOL & IMMUNOL,MONTREAL H3T 1E2,PQ,CANADA. RP GRAZIOSI, C (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 59 TC 419 Z9 422 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 8 PY 1994 VL 265 IS 5169 BP 248 EP 252 DI 10.1126/science.8023143 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV957 UT WOS:A1994NV95700041 PM 8023143 ER PT J AU MORAWETZ, RA DOHERTY, TM GIESE, NA HARTLEY, JW MULLER, W KUHN, R RAJEWSKY, K COFFMAN, R MORSE, HC AF MORAWETZ, RA DOHERTY, TM GIESE, NA HARTLEY, JW MULLER, W KUHN, R RAJEWSKY, K COFFMAN, R MORSE, HC TI RESISTANCE TO MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME (MAIDS) - COMMENT SO SCIENCE LA English DT Note ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; IMMUNE-RESPONSES; MICE; VIRUS; INFECTION; MOUSE; AIDS; SUSCEPTIBILITY; ACTIVATION; DEFICIENT C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. UNIV COLOGNE,INST GENET,D-50931 COLOGNE,GERMANY. RP MORAWETZ, RA (reprint author), NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892, USA. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 25 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 8 PY 1994 VL 265 IS 5169 BP 264 EP 266 DI 10.1126/science.8023146 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV957 UT WOS:A1994NV95700047 PM 8023146 ER PT J AU PETTIT, GR CICHACZ, ZA HERALD, CL GAO, F BOYD, MR SCHMIDT, JM HAMEL, E BAI, RL AF PETTIT, GR CICHACZ, ZA HERALD, CL GAO, F BOYD, MR SCHMIDT, JM HAMEL, E BAI, RL TI ANTINEOPLASTIC AGENTS-300 - ISOLATION AND STRUCTURE OF THE RARE HUMAN CANCER INHIBITORY MACROCYCLIC LACTONES SPONGISTATIN-8 AND SPONGISTATIN-9 SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID MARINE AB Two trace (0.7 and 2.2 x 10(-7)% yields) potent antineoplastic macrocyclic lactones termed spongistatins 8 (2a) and 9 (2b) have been isolated from the African marine sponge Spirastrella spinispirulifera and found to be very potent inhibitors of glutamate-induced tubulin polymerization. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 22 TC 82 Z9 83 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD JUL 7 PY 1994 IS 13 BP 1605 EP 1606 DI 10.1039/c39940001605 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NV804 UT WOS:A1994NV80400045 ER PT J AU VANDEWOUDE, GF AF VANDEWOUDE, GF TI EMBRYOLOGY - ON THE LOSS OF MOS SO NATURE LA English DT Editorial Material ID MAP KINASE; CELL-CYCLE; MATURATION; METAPHASE; OOCYTES; ARREST RP VANDEWOUDE, GF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,POB B,FREDERICK,MD 21702, USA. NR 14 TC 11 Z9 11 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 7 PY 1994 VL 370 IS 6484 BP 20 EP 21 DI 10.1038/370020a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV711 UT WOS:A1994NV71100032 PM 8015598 ER PT J AU LIE, RT WILCOX, AJ SKJAERVEN, R AF LIE, RT WILCOX, AJ SKJAERVEN, R TI A POPULATION-BASED STUDY OF THE RISK OF RECURRENCE OF BIRTH-DEFECTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLEFT-PALATE; MALFORMATIONS; LIP AB Background. Certain birth defects are known to recur in families, but most estimates of the risk of recurrence have come from clinic-based studies. In this study we estimated the risk of recurrent birth defects using a population-based registry. Methods. The study was based on the records of the first and second infants delivered by 371,933 women from 1967 through 1989. The records are maintained by the Medical Birth Registry of Norway. For the 9192 women whose first infant had a birth defect, we determined the relative risk of similar and dissimilar defects in the second infant. The reference population was women whose first infant had no defect. Results. Among first infants, 2.5 percent had a birth defect. The mothers of affected first infants were 2.4 times as likely as other women to have second infants with any registered defect. This increased risk was due primarily to an increased (7.6 times higher) risk of the same defect in the second infant as in the first (95 percent confidence interval, 6.5 to 8.8) and secondarily to a slightly increased (1.5 times higher) risk of a different defect in the second infant (95 percent confidence interval, 1.3 to 1.7). Among the women who lived in the same municipality during both pregnancies, the relative risk of having a second infant with the same defect was 11.6, as compared with 5.1 among the women who moved to another municipality after the birth of their first infant (P<0.001). Conclusions. Among women whose first infant has a birth defect, the risk of the same defect in the second infant is substantially increased and the risk of a different. defect in the second infant is slightly increased. Environment plays a strong part in repeated defects. C1 UNIV BERGEN,MED INFORMAT & STAT SECT,BERGEN,NORWAY. NATL INST PUBL HLTH,OSLO,NORWAY. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP LIE, RT (reprint author), HAUKELAND HOSP,MED BIRTH REGISTRY NORWAY,MFH BLDG,N-5021 BERGEN,NORWAY. OI Wilcox, Allen/0000-0002-3376-1311 NR 19 TC 88 Z9 90 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 7 PY 1994 VL 331 IS 1 BP 1 EP 4 DI 10.1056/NEJM199407073310101 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NU951 UT WOS:A1994NU95100001 PM 8202094 ER PT J AU WHITE, A ANDREWS, E ELDRIDGE, R DICKERSON, M TILSON, H ELKINS, M DAI, W HURN, B ALEXANDER, ER FOX, H GARCIA, P ROGERS, A AF WHITE, A ANDREWS, E ELDRIDGE, R DICKERSON, M TILSON, H ELKINS, M DAI, W HURN, B ALEXANDER, ER FOX, H GARCIA, P ROGERS, A TI BIRTH OUTCOMES FOLLOWING ZIDOVUDINE THERAPY IN PREGNANT-WOMEN (REPRINTED FROM MMWR, VOL 43, PG 409, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 HOFFMANN LA ROCHE INC,DIV DRUG SAFETY,NUTLEY,NJ. WELLCOME RES LABS,CLIN & SAFETY SURVEILLANCE SERV,BECKENHAM,KENT,ENGLAND. SEATTLE KING CTY HLTH DEPT,SEATTLE,WA. COLUMBIA PRESBYTERIAN MED CTR,DEPT OBSTET & GYNECOL,NEW YORK,NY 10032. PRENTICE HOSP,CHICAGO,IL. NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD. NIH,NATL CTR PREVENT SERV,DIV SEXUALLY TRANSMITTED DIS & HIV PREVENT,BETHESDA,MD. NATL CTR INFECT DIS,DIV HIV AIDS,BETHESDA,MD. CTR DIS CONTROL,NATL CTR ENVIRONM HLTH,DIV BIRTH DEFECTS & DEV DISABIL,BETHESDA,MD. RP WHITE, A (reprint author), BURROUGHS WELLCOME CO,INT DIV SURVEILLANCE EPIDEMIOL & ECON RES,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 6 PY 1994 VL 272 IS 1 BP 17 EP 17 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NU485 UT WOS:A1994NU48500010 ER PT J AU BIKKINA, M LEVY, D EVANS, JC LARSON, MG BENJAMIN, EJ WOLF, PA CASTELLI, WP AF BIKKINA, M LEVY, D EVANS, JC LARSON, MG BENJAMIN, EJ WOLF, PA CASTELLI, WP TI LEFT-VENTRICULAR MASS AND RISK OF STROKE IN AN ELDERLY COHORT - THE FRAMINGHAM HEART-STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HYPERTROPHY; ECHOCARDIOGRAPHY; CRITERIA; DISEASE; EVENTS AB Objective.-To evaluate the association of echocardiographically determined left ventricular mass (LVM) with incidence of stroke or transient ischemic attack in an elderly cohort. Design.-Cohort study with a follow-up period of 8 years. Setting.-Population-based sample. Subjects.-Elderly original cohort subjects of the Framingham Heart Study who were free of cerebrovascular disease and atrial fibrillation at the 16th biennial examination and who had adequate echocardiograms. This group consisted of 447 men (mean age, 67.8 years; range, 60 to 90 years) and 783 women (mean age, 69.2 years; range 59 to 90 years). Main Outcome Measures.-Age-adjusted 8 year incidence of stroke was examined as a function of baseline quartiles of LVM-to-height ratio. Proportional hazards regression was used in multivariate analyses to assess risk of stroke as a function of LVM-to-height ratio quartile, adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and blood lipid levels. Results.-Among the 1230 subjects eligible, 89 cerebrovascular disease events (62 strokes and 27 transient ischemic attacks) occurred during follow-up. In men, 8-year age-adjusted incidence of cerebrovascular events was 18.4% in the highest quartile of LVM-to-height ratio and 5.2% in the lowest quartile. Corresponding values in women were 12.2% and 2.9%. The hazard ratio for cerebrovascular events comparing highest to lowest quartile of LVM-to-height ratio was 2.72 (95% confidence interval [CI], 1.39 to 5.36) after adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and the ratio of total cholesterol to high-density lipoprotein cholesterol. After adjusting for age, sex, and cardiovascular disease risk factors, the hazard ratio for cerebrovascular events was 1.45 (95% CI, 1.17 to 1.80) for each quartile increment of LVM-to-height ratio. Conclusions.-Echocardiographically determined LVM-to-height ratio offers prognostic information beyond that provided by traditional cerebrovascular disease risk factors. Echocardiography provides information that facilitates identification of individuals at high risk for stroke and transient ischemic attack. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NHLBI,BETHESDA,MD. BOSTON UNIV,SCH MED,DIV EPIDEMIOL & PREVENT MED,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV CARDIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV NEUROL,BOSTON,MA 02118. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [2-RO1-NS-17950-12] NR 30 TC 219 Z9 224 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 6 PY 1994 VL 272 IS 1 BP 33 EP 36 DI 10.1001/jama.272.1.33 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NU485 UT WOS:A1994NU48500026 PM 8007076 ER PT J AU STEEG, PS ALLEY, MC GREVER, MR AF STEEG, PS ALLEY, MC GREVER, MR TI AN ADDED DIMENSION - WILL 3-DIMENSIONAL CULTURES IMPROVE OUR UNDERSTANDING OF DRUG-RESISTANCE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BASEMENT-MEMBRANE; ALKYLATING-AGENTS; GROWTH; DIFFERENTIATION; SPHEROIDS; LINE C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP STEEG, PS (reprint author), NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,WOMENS CANC SECT,BLDG 10,SUITE 2A33,BETHESDA,MD 20892, USA. NR 18 TC 12 Z9 12 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 JUL 6 PY 1994 VL 86 IS 13 BP 953 EP 955 DI 10.1093/jnci/86.13.953 PG 3 WC Oncology SC Oncology GA NU486 UT WOS:A1994NU48600001 PM 8007014 ER PT J AU INSKIP, PD STOVALL, M FLANNERY, JT AF INSKIP, PD STOVALL, M FLANNERY, JT TI LUNG-CANCER RISK AND RADIATION-DOSE AMONG WOMEN TREATED FOR BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID A-BOMB SURVIVORS; HODGKINS-DISEASE; RADIOTHERAPY; MORTALITY; THERAPY; SURGERY AB Background: Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose, Purpose: This study evaluated the longterm risk of lung cancer among women treated with radiation for breast cancer. Methods: In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. Results: For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. Conclusions: Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. Implications: Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10 000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects. C1 NCI,DIV CANC ETIOL,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIAT PHYS,HOUSTON,TX. CONNECTICUT TUMOR REGISTRY,DEPT HLTH SERV,HARTFORD,CT. NR 29 TC 90 Z9 92 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 6 PY 1994 VL 86 IS 13 BP 983 EP 988 DI 10.1093/jnci/86.13.983 PG 6 WC Oncology SC Oncology GA NU486 UT WOS:A1994NU48600011 PM 8007020 ER PT J AU CHU, KC TARONE, RE CHOW, WH HANKEY, BF RIES, LAG AF CHU, KC TARONE, RE CHOW, WH HANKEY, BF RIES, LAG TI TEMPORAL PATTERNS IN COLORECTAL-CANCER INCIDENCE, SURVIVAL, AND MORTALITY FROM 1950 THROUGH 1990 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FECAL OCCULT BLOOD; LARGE-BOWEL CANCER; COLON CANCER; UNITED-STATES; PHYSICAL-ACTIVITY; RISK-FACTORS; SCREENING SIGMOIDOSCOPY; SEX-DIFFERENCES; COHORT MODELS AB Background: Colorectal cancer mortality rates among U.S. white males remained relatively constant from 1950 through 1984 but declined sharply from 1985 through 1990. Those for U.S. white females decreased consistently from 1950 through 1984, with an acceleration of the decline from 1985 through 1990. Purpose: A study was planned to investigate patterns in incidence, survival, and mortality rates over time in order to examine possible reasons for the gender difference in mortality trends and for the decrease in the slope of the mortality trends for both males and females in the late 1980s. Methods: Incidence and survival data from the Connecticut Cancer Registry were examined to investigate the gender differences in mortality rates from 1950 through 1981. Incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) Program were investigated to examine reasons for the abrupt downturn in mortality rates for both white males and white females beginning around 1985. Results: During the period 1950 through 1984, the colorectal cancer incidence rates in Connecticut increased for males and declined slightly for females. Survival rates were similar for bath sexes, increasing on average over 1% per year for both females and males from 1950 through 1984. Examination of SEER data from 1975 through 1990 revealed that for both males and females there were 1) declines in overall incidence and mortality rates beginning in the mid-1980s, 2) steady declines in distant disease incidence rates since 1975, 3) increases in regional disease incidence rates until the early 1980s followed by declines in the late 1980s, and 4) increases in local disease incidence rates until the mid-1980s followed by declines in the late 1980s. Age-period-cohort analyses of mortality rates indicated a statistically significant moderation of colorectal cancer risk with both advancing birth cohorts and recent calendar periods. Conclusions: The gender differences in colorectal cancer mortality rate trends observed from 1950 through 1984 are due to differences in incidence rate trends between males and females. Declining colorectal mortality rates in the late 1980s for males and females appear to reflect improved early detection. The peaking and subsequent decline of stage-specific incidence rates at later years for successively lower stage indicate sequential stage shifts as cancers are detected increasingly earlier over time. The increased use of sigmoidoscopy and fecal occult blood tests (triggering colonoscopy) appears to have played an important role in reducing colorectal cancer mortality. Improvements in birth cohort trends in risk for colorectal cancer for each sex suggest that lifestyle changes may have also contributed to the steady reductions in colorectal cancer mortality. C1 NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. RP CHU, KC (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EXECUT PLAZA N,RM 305,BETHESDA,MD 20892, USA. NR 60 TC 143 Z9 143 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 6 PY 1994 VL 86 IS 13 BP 997 EP 1006 DI 10.1093/jnci/86.13.997 PG 10 WC Oncology SC Oncology GA NU486 UT WOS:A1994NU48600013 PM 7980765 ER PT J AU BARRY, JA GAWRISCH, K AF BARRY, JA GAWRISCH, K TI DIRECT NMR EVIDENCE FOR ETHANOL BINDING TO THE LIPID-WATER INTERFACE OF PHOSPHOLIPID-BILAYERS SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; MEDIATED ION CURRENT; DEUTERIUM NMR; SIGNAL TRANSDUCTION; NEUROBLASTOMA-CELLS; BIOLOGIC MEMBRANES; NORMAL-ALKANOLS; MODEL MEMBRANE; ALCOHOL; PHASE AB The mechanisms behind the membrane-mediated effects of ethanol were examined via the interaction of ethanol with phospholipid bilayers at hydration levels of 10-12 water molecules per lipid. H-2 and P-31 nuclear magnetic resonance (NMR) spectroscopy was used to monitor deuterated water and ethanol and the headgroups and acyl chains of neutral phospholipids. Ethanol was found to interact strongly with both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers, giving H-2 NMR quadrupolar splittings for CH3CD2OH between 6.3 and 9.4 kHz. The quadrupolar splittings for ethanol in gel-phase lipids remained well resolved and were not significantly larger than those in the L(alpha) phase, suggesting that little or no ethanol was bound in the hydrocarbon interior of the bilayer. Ethanol binding significantly altered the orientation of the lipid headgroups, as shown with headgroup-deuterated PC bilayers. The entire lengths of the acyl chains were significantly disordered by the ethanol interaction, evidenced by significant reductions in the H-2 NMR order parameters of the chains. The disordering corresponds to an increase in the area per lipid by an estimated 6% with one ethanol molecule per lipid, and a total of 18% with a second ethanol per lipid. This pronounced area increase is presumably caused by the disruption of lipid packing in the rigid region of the glycerol backbone rather than in the acyl chains, since the order of hydrocarbon chains is not affected to a significant degree by incorporation of alkanes and long-chain alcohols into the hydrocarbon interior. From these data it was concluded that ethanol interacts with phospholipid bilayers at the lipid-water interface (consisting of the headgroup, glycerol backbone, and uppermost chain methylene groups) rather than in the hydrocarbon interior. An interfacial binding of ethanol that is also capable of disordering the entire length of the acyl chains could explain the small ethanol-induced fluidization of membrane lipids that has been reported frequently in the literature. RP BARRY, JA (reprint author), NIAAA,MEMBRANE BIOCHEM & BIOPHYS,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 49 TC 141 Z9 143 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 5 PY 1994 VL 33 IS 26 BP 8082 EP 8088 DI 10.1021/bi00192a013 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV423 UT WOS:A1994NV42300013 PM 8025114 ER PT J AU KNEPPER, MA AF KNEPPER, MA TI THE AQUAPORIN FAMILY OF MOLECULAR WATER CHANNELS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Note ID MEDULLARY COLLECTING DUCT; REGULATED UREA TRANSPORTER; CELL CHIP28 PROTEIN; RAT-KIDNEY; PERMEABILITY; LOCALIZATION; EXPRESSION; INHIBITION; SEGMENTS; CLONING RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 34 TC 163 Z9 169 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6255 EP 6258 DI 10.1073/pnas.91.14.6255 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000003 PM 7517546 ER PT J AU GRALNICK, HR WILLIAMS, S MCKEOWN, LP HANSMANN, K FENTON, JW KRUTZSCH, H AF GRALNICK, HR WILLIAMS, S MCKEOWN, LP HANSMANN, K FENTON, JW KRUTZSCH, H TI HIGH-AFFINITY ALPHA-THROMBIN BINDING TO PLATELET GLYCOPROTEIN-IB-ALPHA - IDENTIFICATION OF 2 BINDING DOMAINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE THROMBOSIS; BLOOD COAGULATION ID HEPARIN COFACTOR-II; VONWILLEBRAND-FACTOR; RECEPTOR ACTIVATION; PEPTIDES; GLYCOCALICIN; SPECIFICITY; INHIBITION; MECHANISM; SURFACE; LIGAND AB alpha-Thrombin binding to and activation of platelets are of major importance in the initiation of physiologic thrombi and in the genesis of arterial thrombus formation. We have studied the site(s) and affinity of thrombin binding to human platelets. Our studies of the peptide inhibition of thrombin binding indicate that the glycoprotein Ib alpha binding site is of high affinity, K-d approximate to 10(-10) M, while the seven-trans-membrane-domain site is a moderate-affinity thrombin binding site, K-d approximate to 10(-8) M. Further studies to modulate the high- or moderate-affinity thrombin binding can be directed to a specific class of sites. This would allow partial or total inhibition of specific thrombin-platelet interaction(s) in different clinical settings. C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LAB RES,ALBANY,NY 12201. NCI,PATHOL LAB,BETHESDA,MD 20892. RP GRALNICK, HR (reprint author), NIH,SERV HEMATOL,BLDG 10,ROOM 2C390,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL13160] NR 34 TC 65 Z9 65 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 JUL 5 PY 1994 VL 91 IS 14 BP 6334 EP 6338 DI 10.1073/pnas.91.14.6334 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000020 PM 8022782 ER PT J AU KAWAMURA, M MCVICAR, DW JOHNSTON, JA BLAKE, TB CHEN, YQ LAL, BK LLOYD, AR KELVIN, DJ STAPLES, JE ORTALDO, JR OSHEA, JJ AF KAWAMURA, M MCVICAR, DW JOHNSTON, JA BLAKE, TB CHEN, YQ LAL, BK LLOYD, AR KELVIN, DJ STAPLES, JE ORTALDO, JR OSHEA, JJ TI MOLECULAR-CLONING OF L-JAK, A JANUS FAMILY PROTEIN-TYROSINE KINASE EXPRESSED IN NATURAL-KILLER-CELLS AND ACTIVATED LEUKOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; ZETA-CHAIN; INTERFERON-ALPHA/BETA; IL-2 RECEPTOR; LYMPHOCYTES-T; MICE LACKING; PHOSPHORYLATION; INTERLEUKIN-2; IDENTIFICATION AB Protein-tyrosine kinases (PTKs) are critical enzymes for receptor-mediated signaling in lymphocytes. Because natural killer (NK) cells are large granular lymphocytes with specialized effector function, we set out to identify PTKs preferentially expressed in these cells. One such PTK was identified and molecularly cloned. The predicted amino acid sequence shows that this kinase lacks SH2 or SH3 domains typical of src family kinases but has tandem nonidentical catalytic domains, indicating that it is a member of the Janus family of PTKs. Immunoprecipitation using antiserum generated against a peptide corresponding to the deduced amino acid sequence of this gene revealed a kinase with a molecular weight of approximate to 125,000. The pattern of expression of this kinase contrasted sharply with that of other Janus kinases, which are ubiquitously expressed. The kinase described in the present study was found to be more limited in its expression; expression was found in NK cells and an NK-like cell line but not in resting T cells or in other tissues. In contrast, stimulated and transformed T cells expressed the gene, suggesting a role in lymphoid activation. Because of its homology and tissue expression, we have tentatively termed this PTK gene L-JAK for leukocyte Janus kinase. C1 NCI,LEUKOCYTE CELL BIOL SECT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI McVicar, Daniel/G-1970-2015 NR 51 TC 213 Z9 221 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6374 EP 6378 DI 10.1073/pnas.91.14.6374 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000028 PM 8022790 ER PT J AU KAWAKAMI, Y ELIYAHU, S DELGADO, CH ROBBINS, PF SAKAGUCHI, K APPELLA, E YANNELLI, JR ADEMA, GJ MIKI, T ROSENBERG, SA AF KAWAKAMI, Y ELIYAHU, S DELGADO, CH ROBBINS, PF SAKAGUCHI, K APPELLA, E YANNELLI, JR ADEMA, GJ MIKI, T ROSENBERG, SA TI IDENTIFICATION OF A HUMAN-MELANOMA ANTIGEN RECOGNIZED BY TUMOR-INFILTRATING LYMPHOCYTES ASSOCIATED WITH IN-VIVO TUMOR REJECTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EXPRESSION CLONING; TUMOR ANTIGEN; GP100; HLA-A2.1; IMMUNOTHERAPY ID METASTATIC MELANOMA; AUTOLOGOUS MELANOMA; MONOCLONAL-ANTIBODY; MELANOCYTIC TUMORS; CDNA; EXPRESSION; LINEAGE; HMB-45; CELLS; GENE AB The cultured T-cell line TIL1200, established from the tumor-infiltrating lymphocytes (TILs) of a patient with advanced metastatic melanoma, recognized an antigen on most HLA-A2(+) melanomas and on all HLA-A2(+) cultured neonatal melanocytes in an HLA-A2 restricted manner but not on other types of tissues or cell lines tested. A cDNA encoding an antigen recognized by TIL1200 was isolated by screening an HLA-A2(+) breast cancer cell line transfected with an expression cDNA library prepared from an HLA-A2(+) melanoma cell line. The nucleotide and amino acid sequences of this cDNA were almost identical to the genes encoding glycoprotein gp100 or Pmel17 previously registered in the GenBank. Expression of this gene was restricted to melanoma and melanocyte cell lines and retina but was not expressed on other fresh or cultured normal tissues or other types bf tumor tested. The cell line transfected with this cDNA also expressed antigen recognized by the melanoma-specific antibody HMB45 that bound to gp100. A synthetic 10-amino acid peptide derived from gp100 was recognized by TIL1200 in the context of HLA-A2.1. Since the administration of TIL1200 plus interleukin 2 resulted in regression of metastatic cancer in the autologous patient, gp100 is a possible tumor rejection antigen and may be useful for the development of immunotherapies for patients with melanoma. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV NIJMEGEN,ST RADBOUD HOSP,DIV TUMOR IMMUNOL,6525 NIJMEGEN,NETHERLANDS. RP KAWAKAMI, Y (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. RI Adema, G.J./H-8007-2014; Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 32 TC 765 Z9 770 U1 3 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6458 EP 6462 DI 10.1073/pnas.91.14.6458 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000045 PM 8022805 ER PT J AU SMITH, MR LIU, YL MATTHEWS, NT RHEE, SG SUNG, WK KUNG, HF AF SMITH, MR LIU, YL MATTHEWS, NT RHEE, SG SUNG, WK KUNG, HF TI PHOSPHOLIPASE C-GAMMA-1 CAN INDUCE DNA-SYNTHESIS BY A MECHANISM INDEPENDENT OF ITS LIPASE ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C ISOZYMES; SH2 DOMAIN; SRC; PHOSPHORYLATION; BINDING; SITE; MUTAGENESIS; ANTIBODIES; RECEPTORS AB Inositol phospholipid-specific phospholipase C (PLC) is involved in several signaling pathways leading to cellular growth and differentiation. Our previous studies reported the induction of DNA synthesis in quiescent NIH 3T3 cells after microinjection of PLC and the inhibition of serum- or Ras-stimulated DNA synthesis by a mixture of monoclonal antibodies to PLC-gamma 1. In the course of our investigation of anti-PLC-gamma 1 monoclonal antibodies, we found that each antibody exerts different inhibitory effects on the phosphatidylinositol-hydrolyzing activity of PLC-gamma 1 and that the inhibition of enzymatic activity does not correlate with the inhibition of DNA synthesis observed in the microinjection assay. PLC-gamma 1 with defective enzymatic activity was synthesized by substituting phenylalanine for histidine within the PLC-gamma 1 catalytic domain at amino acids 335 and 380, and mutant enzymes were expressed using a vaccinia expression system. The mutant enzymes were purified and microinjected into quiescent NIH 3T3 cells to evaluate their mitogenic activity. A moderate induction of DNA synthesis occurred after injection of mutant PLC-gamma 1. This mitogenic activity was inhibited by an antibody (alpha E 8-4) that does not significantly inhibit PLC-gamma 1 enzyme activity, which indicates that something else has to be inhibited. Furthermore, the partial induction of DNA synthesis observed with mutant PLC-gamma 1 was increased to levels seen with wild-type PLC-gamma 1 by coinjection of mutant PLC-gamma 1 with two second messengers, diacylglycerol and inositol trisphosphate. These results suggest that the mitogenic activity of PLC-gamma 1 does not exclusively result from the enzymatic activity of the lipase and that another activity inherent to the PLC-gamma 1 molecule can also induce DNA synthesis in quiescent cells. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 20 TC 100 Z9 100 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6554 EP 6558 DI 10.1073/pnas.91.14.6554 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000065 PM 8022819 ER PT J AU WINK, DA NIMS, RW SAAVEDRA, JE UTERMAHLEN, WE FORD, PC AF WINK, DA NIMS, RW SAAVEDRA, JE UTERMAHLEN, WE FORD, PC TI THE FENTON OXIDATION MECHANISM - REACTIVITIES OF BIOLOGICALLY RELEVANT SUBSTRATES WITH 2 OXIDIZING INTERMEDIATES DIFFER FROM THOSE PREDICTED FOR THE HYDROXYL RADICAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID N-NITROSODIMETHYLAMINE; HYDROGEN-PEROXIDE; IRON; ACID; DEGRADATION; OXIDANT AB The application of kinetic probes that allow one to determine relative reactivities of biologically relevant substrates with oxidizing intermediates in the Fenton reagent H2O2 plus Fe2+ in acidic aqueous solution) is described, These results lead to the conclusion that there are two key intermediates with very different reactivity patterns. One (X) is proposed to be an iron complex formed via direct reaction of H2O2 with Fe2+, which reacts with N-nitrosodimethylamine to generate a strong transient absorption at 450 nm. This provides a sensitive spectrophotometric probe of the competitive reactivities toward X of biologically relevant substrates such as nucleic acid components and amino acids. The second intermediate (Y) is probed by its oxidation of the Ru(bpy)(3)(2+) ion (bpy = 2,2' bipyridine) to a product with an absorption band centered at 500 nm. In the absence of other substrates, Ru(bpy)(3)(2+) is oxidized at rates independent of the Ru concentration, but the product yield is diminished by competing reactions with substrates that can intercept X. Competition studies demonstrate reactivity patterns for X and Y that are clearly distinct from the pattern predicted For the hydroxyl radical, the intermediate commonly invoked in discussions of Fenton oxidations. These data require reevaluation of the mechanisms by which the Fenton reagent oxidizes biological substrates. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. RP WINK, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 24 TC 127 Z9 131 U1 3 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6604 EP 6608 DI 10.1073/pnas.91.14.6604 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000075 PM 8022825 ER PT J AU YANG, XJ KAUFMAN, S AF YANG, XJ KAUFMAN, S TI HIGH-LEVEL EXPRESSION AND DELETION MUTAGENESIS OF HUMAN TRYPTOPHAN-HYDROXYLASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIVER PHENYLALANINE-HYDROXYLASE; RAT TYROSINE-HYDROXYLASE; ESCHERICHIA-COLI; CLONED ENZYME; PURIFICATION; CDNA; SEQUENCE; DOMAINS; CELLS; IRON AB Human tryptophan hydroxylase has been expressed as a soluble and active form in Escherichia coli by fusion with an affinity tag, maltose-binding protein. The fusion protein has been purified to near homogeneity by affinity chromatography on crosslinked amylose resin. The purified fusion protein has a specific activity of 86 nmol of 5-hydroxy-tryptophan per min per mg of fusion protein. A series of truncation mutants have also been made to explore the domain organization of tryptophan hydroxylase. All deletion mutants were subject to affinity purification and kinetic characterization. While removal of the N-terminal 164 amino acids completely inactivates the enzyme, deletion of the first 91 residues results in a 7-fold reduction in specific activity. From the C terminus, deletion of 36, 55, or 122 amino acids abolishes the activity, whereas deletion of 19 residues decreases the specific activity by approximate to 11-fold. These results are consistent with a model for tryptophan hydroxylase in which the enzyme consists of an N-terminal regulatory domain, a catalytic core, and a small C-terminal region of uncertain but important function. RP YANG, XJ (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 31 TC 49 Z9 50 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6659 EP 6663 DI 10.1073/pnas.91.14.6659 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000086 PM 8022832 ER PT J AU DEVANE, WA AXELROD, J AF DEVANE, WA AXELROD, J TI ENZYMATIC-SYNTHESIS OF ANANDAMIDE, AN ENDOGENOUS LIGAND FOR THE CANNABINOID RECEPTOR, BY BRAIN MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ARACHIDONIC ACID; ETHANOLAMINE; HIPPOCAMPUS ID MEDIATED SIGNAL-TRANSDUCTION; NEUROBLASTOMA-CELLS; AGONIST; CONSTITUENT; BINDS AB Anandamide, an endogenous eicosanoid derivative (arachidonoylethanolamide), binds to the cannabinoid receptor, a member of the G protein-coupled superfamily. It also inhibits both adenylate cyclase and N-type calcium channel opening. The enzymatic synthesis of anandamide in bovine brain tissue was examined by incubating brain membranes with [C-14]ethanolamine and arachidonic acid. Following incubation and extraction into toluene, a radioactive product was identified which had the same R(f) value as authentic anandamide in several thin-layer chromatographic systems. When structurally similar fatty acid substrates were compared, arachidonic acid exhibited the lowest EC(50) and the highest activity for enzymatic formation of the corresponding ethanolamides. The concentration-response curve of arachidonic acid exhibited a steep slope, and at higher concentrations arachidonate inhibited enzymatic activity. When brain homogenates were separated into subcellular fractions by sucrose density gradient centrifugation, anandamide synthase activity was highest in fractions enriched in synaptic vesicles, myelin, and microsomal and synaptosomal membranes. When several areas of brain were examined, anandamide synthase activity was found to be highest in the hippocampus, followed by the thalamus, cortex, and striatum, and lowest in the cerebellum, pens, and medulla. The ability of brain tissue to enzymatically synthesize anandamide and the existence of specific receptors for this eicosanoid suggest the presence of anandamide-containing (anandaergic) neurons. RP DEVANE, WA (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. NR 25 TC 192 Z9 193 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6698 EP 6701 DI 10.1073/pnas.91.14.6698 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000094 PM 8022836 ER PT J AU FAN, P AF FAN, P TI ANTAGONISM BY FORSKOLIN OF THE 5-HT3 RECEPTOR-MEDIATED CURRENT IN NODOSE GANGLION NEURONS IS INDEPENDENT OF CYCLIC-AMP SO BRAIN RESEARCH LA English DT Article DE NODOSE GANGLION; 5-HT3 RECEPTOR; PATCH-CLAMP; FORSKOLIN; CYCLIC AMP; DESENSITIZATION ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CELLS; CAMP; CHANNELS; DESENSITIZATION; INHIBITION; ACTIVATION; MODULATION; TRANSPORT; CYCLASE AB The effect of forskolin on the inward current mediated by 5-HT3 receptors (5-HT current) was investigated in rat nodose ganglion neurons. Forskolin inhibited the peak amplitude of the 5-HT current and increased current desensitization in a dose-dependent manner. Dideoxyforskolin, which does not stimulate adenylate cyclase, had a similar inhibitory effect on the 5-HT current. The effect of forskolin was neither mimicked by intracellular application of exogenous cyclic AMP (0.5 to 3 mM) nor occluded by intracellular forskolin (30 mu M) or protein kinase inhibitor H-7 (100 mu M). Intracellular applications of forskolin, cyclic AMP or H-7 had no effect on 5-HT current. Data suggest that forskolin acted at an extracellular site on 5-HT3 receptors and this effect of forskolin was not mediated by cyclic AMP-dependent processes. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 4 PY 1994 VL 650 IS 1 BP 16 EP 19 DI 10.1016/0006-8993(94)90201-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NW228 UT WOS:A1994NW22800003 PM 7525015 ER PT J AU DALY, JW SHI, D WONG, V NIKODIJEVIC, O AF DALY, JW SHI, D WONG, V NIKODIJEVIC, O TI CHRONIC EFFECTS OF ETHANOL ON CENTRAL ADENOSINE FUNCTION OF MICE SO BRAIN RESEARCH LA English DT Note DE ETHANOL; ADENOSINE RECEPTOR; LOCOMOTOR ACTIVITY; CALCIUM CHANNEL; CAFFEINE; DIHYDROPYRIDINE ID INDUCED MOTOR INCOORDINATION; SHORT-SLEEP MICE; LOCOMOTOR-ACTIVITY; CALCIUM CHANNELS; MOUSE-BRAIN; LONG-SLEEP; TOLERANCE; RECEPTORS; CAFFEINE; SEROTONIN AB Chronic ingestion of 5% ethanol had no significant effect on open field locomotor of NIH Swiss strain male mice, nor were the depressant effects of a non-selective adenosine receptor agonist, NECA, or the stimulant effects of a non-selective antagonist, caffeine significantly altered. The density of cerebral cortical A(1)-adenosine receptors and of nitrendipine binding sites on calcium channels were significantly increased after chronic ethanol, while the density of striatal A(2a)-adenosine receptors were unchanged. The locomotor stimulant effects of ethanol (2.5 g/kg) were slightly decreased after chronic ethanol, but were markedly reduced in mice after chronic caffeine ingestion. The results suggest some involvement of adenosine systems in the effects of ethanol. RP DALY, JW (reprint author), NIH,BIOORGAN CHEM LAB,BLDG 8,RM 1A17,BETHESDA,MD 20892, USA. NR 24 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 4 PY 1994 VL 650 IS 1 BP 153 EP 156 DI 10.1016/0006-8993(94)90219-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NW228 UT WOS:A1994NW22800021 PM 7953667 ER PT J AU COAN, EJ GALDZICKI, Z RAPOPORT, SI AF COAN, EJ GALDZICKI, Z RAPOPORT, SI TI EFFECTS OF NERVE GROWTH-FACTOR ON WHOLE-CELL CURRENTS AND OTHER ELECTRICAL MEMBRANE-PROPERTIES IN CULTURED DORSAL-ROOT GANGLION NEURONS FROM NORMAL AND TRISOMY-16 MICE SO BRAIN RESEARCH LA English DT Note DE ACTION POTENTIAL; MEMBRANE CURRENT; DOWN SYNDROME; DORSAL ROOT GANGLION; NERVE GROWTH FACTOR; TRISOMY 16 MOUSE; TRISOMY 21 ID ACTION-POTENTIAL DURATION; SENSORY NEURONS; DOWNS-SYNDROME; HUMAN FETUSES; MOUSE FETUS; FETAL MOUSE; ABNORMALITIES; DEMENTIA; MODEL AB The trisomy 16 mouse is considered to be a model of human trisomy 21 (Down syndrome). Dorsal root ganglia (DRG) from trisomy 16 and diploid control fetuses were cultured in the presence of nerve growth factor (NGF) for 10 days, after which NGF was withdrawn from 50% of the dishes. Withdrawing NGF at 10 days did not affect the survival rate of either trisomy 16 or control neurons. With or without NGF, trisomy 16 neurons had a significantly larger inward current (171%, 163%) and larger inward conductance (156%, 166%), a faster rate of depolarization (219%, 149%), and a shorter duration of the action potential (83%, 81%) than control neurons, indicating that these parameters are determined solely by the trisomic state. In the absence of NGF, the outward conductance was significantly larger (143%), and the rate of repolarization was faster (131%), in trisomy cells compared to controls. Withdrawing NGF resulted in a smaller outward conductance (86%) in control neurons and a larger outward conductance (132%) and faster rate of repolarization (118%) in trisomy neurons, indicating that these parameters are NGF-dependent, and that trisomy and control neurons exhibit a differential sensitivity to NGF. This is the first report of a differential sensitivity of trisomic and control neurons to NGF, and demonstrates significant abnormalities in active electrical membrane properties of trisomic DRG neurons. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 4 PY 1994 VL 650 IS 1 BP 161 EP 165 DI 10.1016/0006-8993(94)90221-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA NW228 UT WOS:A1994NW22800023 PM 7953669 ER PT J AU WANG, JB JOHNSON, PS IMAI, Y PERSICO, AM OZENBERGER, BA EPPLER, CM UHL, GR AF WANG, JB JOHNSON, PS IMAI, Y PERSICO, AM OZENBERGER, BA EPPLER, CM UHL, GR TI CDNA CLONING OF AN ORPHAN OPIATE RECEPTOR GENE FAMILY MEMBER AND ITS SPLICE VARIANT SO FEBS LETTERS LA English DT Article DE G-LINKED RECEPTOR; MORPHINE; 7-TRANSMEMBRANE DOMAIN; HYPOTHALAMUS; ALTERNATIVE SPLICING ID DELTA-OPIOID RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; BINDING-SITES; BRAIN; RAT; MORPHINE; SUBTYPE; CELLS AB Radioligand binding and cDNA homology studies have suggested the existence of opiate receptors distinct from the recently-cloned mu, delta and kappa receptors. XORIS, a rat brain cDNA whose predicted translation product displays 67-72% homology with those encoded by mu 1, delta 1 and kappa 1 opiate receptor cDNAs, was constructed from two partial cDNAs identified through cDNA homology approaches. A longer XORIL variant of this cDNA was also identified by polymerase chain reaction studies using genomic DNA and cDNA from brain and peripheral tissues. XOR1 mRNA is most highly expressed in hypothalamus. COS cell expression of both clones confers neither robust binding of opiate ligands nor reproducible opiate inhibition of forskolin-stimulated adenylate cyclase. These studies identify an orphan clone that helps to define features of the opiate receptor gene family, including apparent differential splicing and expression in peripheral tissues. C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,NATL INST GEN MED SCI,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. AMER CYANAMID CO,DIV AGR RES,PRINCETON,NJ 08543. NR 24 TC 334 Z9 342 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 1994 VL 348 IS 1 BP 75 EP 79 DI 10.1016/0014-5793(94)00557-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NW534 UT WOS:A1994NW53400016 PM 8026588 ER PT J AU SHAPIRA, H WAY, J LIPINSKY, D ORON, Y BATTEY, JF AF SHAPIRA, H WAY, J LIPINSKY, D ORON, Y BATTEY, JF TI NEUROMEDIN-B RECEPTOR, EXPRESSED IN XENOPUS-LAEVIS OOCYTES, SELECTIVELY COUPLES TO G(ALPHA-Q) AND NOT G(ALPHA-11) SO FEBS LETTERS LA English DT Article DE G-PROTEIN; NEUROMEDIN B RECEPTOR; GASTRIN-RELEASING PEPTIDE RECEPTOR; XENOPUS OOCYTE ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE HYDROLYSIS; NUCLEOTIDE-BINDING PROTEIN; PHOSPHOLIPASE-C ACTIVITY; SWISS 3T3 CELLS; ALPHA-SUBUNITS; BOMBESIN RECEPTOR; ACETYLCHOLINE-RECEPTOR; MUSCARINIC RECEPTOR; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING AB G-proteins of the q family have been implicated as mediators of bombesin receptors action. We cloned Xenopus G(alpha q) and G(alpha 11) and specifically disrupted the synthesis of either protein with selective antisense oligonucleotides. G(alpha q) antisense inhibited responses mediated by neuromedin B receptor (NMB-R) by 74%, though not by gastrin-releasing peptide receptor (GRP-R). G(alpha 11) antisense had little effect on either GRP-R- or NMB-R-mediated responses. This suggests that NMB-R couples to G(alpha q) and that GRP-R and NMB-R show distinct G-protein coupling preferences in the Xenopus oocyte. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD. RP SHAPIRA, H (reprint author), TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 RAMAT AVIV,ISRAEL. NR 34 TC 43 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 1994 VL 348 IS 1 BP 89 EP 92 DI 10.1016/0014-5793(94)00570-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NW534 UT WOS:A1994NW53400018 PM 8026589 ER PT J AU KOVACS, JA KOVACS, AAS AF KOVACS, JA KOVACS, AAS TI PCP PROPHYLAXIS IN PEDIATRIC HIV-INFECTION - TIME FOR A CHANGE SO LANCET LA English DT Editorial Material ID PNEUMOCYSTIS-CARINII PNEUMONIA; CHILDREN C1 UNIV SO CALIF,LOS ANGELES CTY MED CTR,COMPREHENS MATERNAL CHILD HIV MANAGEMENT & RES CT,LOS ANGELES,CA 90033. RP KOVACS, JA (reprint author), NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 2 PY 1994 VL 344 IS 8914 BP 5 EP 6 DI 10.1016/S0140-6736(94)91042-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NU917 UT WOS:A1994NU91700005 PM 7912309 ER PT J AU STURA, EA SATTERTHWAIT, AC CALVO, JC KASLOW, DC WILSON, IA AF STURA, EA SATTERTHWAIT, AC CALVO, JC KASLOW, DC WILSON, IA TI REVERSE SCREENING SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article; Proceedings Paper CT 5th International Conference on the Crystallization of Biological Macromolecules (ICCBM)/National-Institute-of-Health Membrane Crystallization Workshop CY AUG 08-13, 1993 CL SAN DIEGO, CA SP NIH ID PRELIMINARY CRYSTALLOGRAPHIC DATA; GROWTH-FACTOR; STEROID FAB'; CRYSTALLIZATION; COMPLEXES; PROTEINS; PHOSPHOGLUCOMUTASE; CRYSTALS; SEQUENCE; ANTIBODY AB Major emphasis has been placed in recent years on kits for screening crystallization conditions of macromolecules. Such approaches have undoubtedly speeded up the initial screening and, to a certain extent, helped in reducing the amount of protem required for die initial survey. Factorial screening techniques, either full-factorial or sparse-matrix approaches, have proved successful in the crystallization of many proteins. However, in cases where the amount of protein is limited a systematic approach based on an a priori choice of precipitants may be preferable to an extensive search. The approach described here targets such situations. The approach consists of the determination of the solubility characteristics of the macromolecule under study as a function of precipitant and macromolecule concentrations to define a working range for these parameters. Conditions under which the protein is highly supersaturated, and hence more conducive to nucleation, are established so as to favor die formation of an initial stable nucleus which can be one of the dominant problems that hinders successful crystallization of proteins. Later, changes in solubility as a function of pH and as a result of the introduction of additives are evaluated. In addition, when ligands are available for the formation of macromolecular complexes, screening of different complexes is used as a means to increase the probability of obtaining crystals. Solubility information derived from one, or more, complexes that have been screened can be used for comparison and to aid in the crystallization of other complexes. Cross-seeding between complexes is an intrinsic part of the method and provides an efficient way of obtaining crystals when spontaneous nucleation is hard to achieve. In the example presented here, reverse screening has enabled the production of crystals of several peptide complexes with an anti-malaria antibody. C1 NIAID, MALARIA RES LAB, BETHESDA, MD 20892 USA. RP STURA, EA (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 90237 USA. RI STURA, Enrico/A-2793-2010 OI STURA, Enrico/0000-0001-6718-2118 NR 35 TC 51 Z9 51 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1994 VL 50 BP 448 EP 455 DI 10.1107/S0907444994001794 PN 4 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA NY475 UT WOS:A1994NY47500020 PM 15299400 ER PT J AU STURA, EA KANG, AS STEFANKO, RS CALVO, JC KASLOW, DC SATTERTHWAIT, AC AF STURA, EA KANG, AS STEFANKO, RS CALVO, JC KASLOW, DC SATTERTHWAIT, AC TI CRYSTALLIZATION, SEQUENCE AND PRELIMINARY CRYSTALLOGRAPHIC DATA FOR TRANSMISSION-BLOCKING ANTI-MALARIA FAB 4B7 WITH CYCLIC-PEPTIDES FROM THE PFS25 PROTEIN OF PLASMODIUM-FALCIPARUM SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID GROWTH-FACTOR; RECOGNITION; REFINEMENT AB X-ray quality crystals of an Fab fragment from a transmission-blocking monoclonal antibody 4B7 (MAb 4B7) against a sexual stage protein Pfs25 of Plasmodium falciparum were grown as uncomplexed and peptide-complexed forms. Initially, the intact immunoglobulin was crystallized because cleavage with pepsin or papain did not produce a homogeneous product. Further proteolytic trials with elastase produced a suitable Fab fragment from which crystals have been obtained, both for the fire Fab and in complex with cyclic peptides and in the presence of linear peptides. While linear peptides bind to MAb 4B7, cyclic peptides modeled on a predicted beta-hairpin loop of the third EGF-like domain of Pfs25 bind better and readily co-crystallize with the Fab. The genes for the variable domain of the Fab have been cloned, sequenced and the primary amino-acid sequence for the complete Fab deduced. This work explores the use of glycerol as an additive and the modification of the peptide sequence outside the epitope for improving in the crystallization. Data sets have been collected from crystals of several Fab-peptide complexes and from uncomplexed Fab to resolutions ranging from 2.4 to 3.3 angstrom. The packing arrangements of several crystal forms have been determined by molecular replacement, and refinement of their three-dimensional structures is in progress. The three-dimensional structure of this Fab complexed with the various peptides will aid in an understanding of the mode by which this antibody recognizes and prevents transmission of the malaria parasite. C1 NIAID, MALARIA RES LAB, BETHESDA, MD 20892 USA. RP STURA, EA (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI STURA, Enrico/A-2793-2010 OI STURA, Enrico/0000-0001-6718-2118 NR 31 TC 8 Z9 9 U1 1 U2 3 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 1399-0047 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1994 VL 50 BP 535 EP 542 DI 10.1107/S0907444994001356 PN 4 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA NY475 UT WOS:A1994NY47500035 PM 15299415 ER PT J AU STURA, EA SATTERTHWAIT, AC CALVO, JC STEFANKO, RS LANGEVELD, JP KASLOW, DC AF STURA, EA SATTERTHWAIT, AC CALVO, JC STEFANKO, RS LANGEVELD, JP KASLOW, DC TI CRYSTALLIZATION OF AN INTACT MONOCLONAL-ANTIBODY (4B7) AGAINST PLASMODIUM-FALCIPARUM MALARIA WITH PEPTIDES FROM THE PFS25 PROTEIN ANTIGEN SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PRELIMINARY CRYSTALLOGRAPHIC DATA; SEGMENTAL FLEXIBILITY; 3-DIMENSIONAL STRUCTURE; PRIMARY SEQUENCE; IMMUNOGLOBULIN-G; CHIMERIC HUMAN; MOLECULE KOL; BINDING-SITE; FAB REGIONS; AMINO-ACID AB Monoclonal antibody 4B7 is a neutralizing antibody that binds the protein Pfs25 in the sexual stages of the malaria parasite Plasmodium falciparum and completely blocks transmission of the parasite from human serum to the mosquito host. Here we report the identification of the epitope on Pfs25 recognized by 4B7 and the crystallization of the intact murine monoclonal antibody with peptides corresponding to that epitope. This study highlights the importance of ligands in the crystallization of proteins. In this case peptides have been used to modulate the solubility of the peptide-IgG complex and may have provided different or additional crystal contacts to create or enhance a crystalline reticulum. Multiple crystal forms characterize this crystallization and the various peptides, differing both in length and sequence, have been used to investigate how such changes affect nucleation and crystal growth. C1 UNIV UTRECHT, SCH VET MED, UTRECHT, NETHERLANDS. NIAID, MALARIA RES LAB, BETHESDA, MD 20892 USA. RP STURA, EA (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI STURA, Enrico/A-2793-2010 OI STURA, Enrico/0000-0001-6718-2118 NR 40 TC 17 Z9 17 U1 0 U2 3 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 1399-0047 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL 1 PY 1994 VL 50 BP 556 EP 562 DI 10.1107/S0907444994001782 PN 4 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA NY475 UT WOS:A1994NY47500038 PM 15299418 ER PT J AU GUO, XY SPENCER, JW SUESS, PE HICKEY, JE BETTER, WE HERNING, RI AF GUO, XY SPENCER, JW SUESS, PE HICKEY, JE BETTER, WE HERNING, RI TI COGNITIVE BRAIN POTENTIAL ALTERATIONS IN BOYS EXPOSED TO OPIATES - IN-UTERO AND LIFE-STYLE COMPARISONS SO ADDICTIVE BEHAVIORS LA English DT Article ID EVENT-RELATED POTENTIALS; DEFICIT HYPERACTIVITY DISORDER; METHADONE-MAINTAINED WOMEN; EVOKED-POTENTIALS; FOLLOW-UP; SELECTIVE ATTENTION; INFANT INTERACTION; ADDICTED MOTHERS; OFFSPRING BORN; DRUG EXPOSURE AB Several studies have observed that intrauterine exposure to opiates results in emotional and cognitive complications for the child, but genetic and postnatal social-environmental factors may also affect the CNS development of these children. To assess the relative contribution of the in utero and social-environmental (lifestyle) effects of opiate exposure, event-related potentials (ERPs) and performance were studied in three groups of 7- to 12-year-old boys: (1) the in utero/lifestyle group (IU/LS) contained 16 boys who were exposed to opiates (in utero and lived with opiate-abusing mothers, (2) the lifestyle group (LS) included 14 boys who lived with opiate-abusing mothers, and (3) the control group (CON) composed of 13 boys. The cognitive ERP components and task performance were recorded in the Auditory Rare Event Monitoring (AREM) task and the Sternberg Memory task (Sternberg, 1975). On the AREM and Sternberg Memory tasks, P200 component was significantly decreased for the IU/LS and LS groups. On the Sternberg Memory task, percent correct was also significantly impaired in IU/LS and LS groups. The ERP alterations in the boys living with opiate-abusing mothers with and without intrauterine opiate exposure were similar. A dysfunctional social environment may contribute to the cognitive deficits seen in the sons of opiate-abusing mothers. C1 NIDA,ARC,MED AFFAIRS BRANCH,POB 5180,BALTIMORE,MD 21224. NR 52 TC 5 Z9 5 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 1994 VL 19 IS 4 BP 429 EP 441 DI 10.1016/0306-4603(94)90065-5 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA PA401 UT WOS:A1994PA40100009 PM 7992677 ER PT J AU KONINGS, E BLATTNER, WA LEVIN, A BRUBAKER, G SISO, Z SHAO, J GOEDERT, JJ ANDERSON, RM AF KONINGS, E BLATTNER, WA LEVIN, A BRUBAKER, G SISO, Z SHAO, J GOEDERT, JJ ANDERSON, RM TI SEXUAL-BEHAVIOR SURVEY IN A RURAL AREA OF NORTHWEST TANZANIA SO AIDS LA English DT Article DE SURVEY; SEXUAL BEHAVIOR; TRANSMISSION; AGE AT FIRST INTERCOURSE ID HUMAN-IMMUNODEFICIENCY-VIRUS; FRANCISCO MENS HEALTH; CONDOM USE; TRANSMISSION; RISK; INFECTION; WOMEN; AIDS AB Objective: Little is known about variations in patterns of sexual behaviour in different countries, cultures, and subpopulations that determine the spread of HIV-1. Quantitative studies are required to improve understanding. Methods: To assess reported patterns of sexual behaviour, we administered a standardized questionnaire to 416 men and 498 women aged 15-49 years from a rural population in northwest Tanzania. Results: Reported levels of sexual activity were highest in men and among younger age groups. The number of sexual partners and number of sex acts per unit of time were strongly correlated: men reported 10 times as many lifetime partners than women. Frequency of sexual partner exchange plateaued earlier in women (by age 25 years) than in men (by age 35 years). For the great majority, age of first intercourse was 15 years or younger; older subjects were older at first intercourse and had fewer lifetime partners than younger subjects. Conclusions: This age-related pattern suggests that more recent birth cohorts have behaviour patterns that increase the risk of sexually transmitted infectious agents such as HIV. Preventive education programmes should be targeted at young adults, who adopt higher risk profiles of frequent partner exchange linked with first intercourse at an early age. C1 UNIV LONDON IMPERIAL COLL SCI & TECHNOL,PARASITE EPIDEMIOL RES GRP,LONDON,ENGLAND. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. RES TRIANGLE INST,LONDON,ENGLAND. UNIV DAR ES SALAAM,DAR ES SALAAM,TANZANIA. SHIRATI HOSP,SHIRATI,TANZANIA. NATL AIDS COMMISS,DAR ES SALAAM,TANZANIA. FU NCI NIH HHS [NCI-CP-EB-85603-57] NR 20 TC 36 Z9 36 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1994 VL 8 IS 7 BP 987 EP 993 DI 10.1097/00002030-199407000-00018 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU947 UT WOS:A1994NU94700018 PM 7946111 ER PT J AU CARRIER, F MCCARY, JM BAE, I YAROSH, DB FORNACE, AJ AF CARRIER, F MCCARY, JM BAE, I YAROSH, DB FORNACE, AJ TI ACTIVATION OF HIV TYPE-1 LONG TERMINAL REPEAT BY ULTRAVIOLET-LIGHT IS SERUM AND STRAIN-SPECIFIC SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; DNA DAMAGE; INDUCED EXPRESSION; GENE-EXPRESSION; MAMMALIAN-CELLS; HTLV-III/LAV; INDUCTION; TRANSCRIPTION; EVOLUTION AB We have studied the UV responsiveness of xeroderma pigmentosum (XP) and HeLa cell lines transfected with a CAT reporter gene under the control of the HIV-1 LTR promoter. XP fibroblasts grown in 10% newborn bovine serum (NBS) were three times more responsive to UV radiation than cells grown in 10% fetal calf serum (FCS). Moreover, cocultivation of UV-irradiated XP cells with XP cells containing stable integrants of HIV-LTR CAT was found to be more than four times more effective in inducing the CAT activity when cells were maintained in 10% NBS than in 10% FCS. The level of induction was also dependent on the serum concentration. These data indicate that a serum component, possibly a cytokine(s), can enhance the UV response of both irradiated cells and unirradiated cells cocultivated with irradiated cells. The magnitude of UV responsiveness seemed also to be strain dependent. CAT activity for the HIV LTR promoter from the HTLV-IIIB (HN-IIIB) strain was induced more than 30-fold by UV irradiation whereas activity from the LAV-1(BRU) Strain was less than 2-fold. In contrast, both constructs were strongly induced by Tat expression. This indicates that there are differences in the induction mechanism for these two stimuli, even though UV radiation has been pre- viously reported to induce a cellular Tat-like factor (Valerie K, et al., Nature [London] 1988;333:78-81). C1 APPL GENET INC,FREEPORT,NY 11520. RP CARRIER, F (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 34 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 1994 VL 10 IS 7 BP 767 EP 773 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PA515 UT WOS:A1994PA51500001 PM 7986581 ER PT J AU HONKANEN, A CHRAPUSTA, SJ KAROUM, F KORPI, ER AF HONKANEN, A CHRAPUSTA, SJ KAROUM, F KORPI, ER TI ALTERATIONS IN DOPAMINE METABOLISM BY INTRAPERITONEAL ETHANOL IN RATS SELECTED FOR HIGH AND LOW ETHANOL PREFERENCE - A 3-METHOXYTYRAMINE STUDY SO ALCOHOL LA English DT Article DE ETHANOL; DOPAMINE METABOLISM; NUCLEUS ACCUMBENS; 3-METHOXYTYRAMINE; ALCOHOL-PREFERRING RATS; ALCOHOL-AVOIDING RATS ID FREELY MOVING RATS; VENTRAL TEGMENTAL AREA; ALCOHOL-PREFERRING AA; NUCLEUS-ACCUMBENS; FRONTAL-CORTEX; BETA-ENDORPHIN; BRAIN-TISSUE; ION CURRENT; RELEASE; NEURONS AB Effects of an ethanol dose (1 g/kg, IP) on the metabolism of dopamine (DA) in the nucleus accumbens, striatum and hypothalamus of ethanol-naive alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were studied. Rats were sacrificed by focused-beam microwave irradiation of the brain 20 minutes after ethanol administration, and the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), assumed to reflect DA metabolism, and of 3-methoxytyramine (3-MT), assumed to reflect DA release, were measured using gas chromatography-mass spectrometry. Basal striatal DOPAC and HVA concentrations were higher in the AA rats in comparison with ANA rats. Ethanol increased HVA, but not DOPAC, concentration in the nucleus accumbens and striatum, but not in the hypothalamus. There was a significant rat line X ethanol treatment interaction with respect to HVA concentration in the nucleus accumbens. The increase in HVA was higher in the AA than ANA rats. Basal 3-MT concentration was not changed by ethanol, except in the nucleus accumbens, where a significant rat line X ethanol treatment interaction was found. A decrease in 3-MT concentration was only detected in the ANA rats. After inhibition of monoamine oxidase with pargyline hydrochloride (75 mg/kg, IP, 10 min before sacrifice), 3-MT accumulation was decreased by ethanol, especially in the nucleus accumbens of both AA and ANA rat lines as well as in that of nonselected Wistar rats. The results suggest that 1) DA metabolism to DOPAC and KVA is dissociable from DA release as reflected by 3-MT production, 2) ethanol, if anything, reduces DA release, and that 3) the AA and ANA rats differ in their basal DA metabolism and in the ethanol effects thereupon, but not in ethanol-induced changes in DA release. C1 ALKO LTD,BIOMED RES CTR,SF-00101 HELSINKI,FINLAND. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 59 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUL-AUG PY 1994 VL 11 IS 4 BP 323 EP 328 DI 10.1016/0741-8329(94)90099-X PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA NZ446 UT WOS:A1994NZ44600007 PM 7945987 ER PT J AU OBARZANEK, E SCHREIBER, GB CRAWFORD, PB GOLDMAN, SR BARRIER, PM FREDERICK, MM LAKATOS, E AF OBARZANEK, E SCHREIBER, GB CRAWFORD, PB GOLDMAN, SR BARRIER, PM FREDERICK, MM LAKATOS, E TI ENERGY-INTAKE AND PHYSICAL-ACTIVITY IN RELATION TO INDEXES OF BODY-FAT - THE NATIONAL-HEART,-LUNG,-AND-BLOOD-INSTITUTE GROWTH AND HEALTH STUDY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE FAT INTAKE; ENERGY INTAKE; TELEVISION WATCHING; OBESITY; BODY MASS INDEX; SKINFOLD THICKNESS; PHYSICAL ACTIVITY ID CARDIOVASCULAR-DISEASE; CHILDREN; OBESITY; TELEVISION; RISK; SCHOOLCHILDREN; ADOLESCENTS; NUTRITION; FITNESS; FATNESS AB The relationship between energy intake, physical activity, and body fat was investigated in the baseline visit of 2379 black and white girls aged 9-10 y enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study. Three-day food records, three-day physical activity diaries, physical-activity-patterns questionnaires, and an assessment of the number of hours of television and video watched were obtained. Multivariate-regression analyses showed that age, the number of hours of television and video watched, the percent of energy from saturated fatty acids, and the activity-patterns score best explained the variation in body mass index and sum of three skinfold-thickness measurements for black girls. The best model for white girls included age, the number of hours of television and video watched, and the percent of energy from total fat. These results indicate that body fatness is related to energy intake and expenditure in both black and white girls. Longitudinal studies will help assess the value of these variables in predicting changes in body fat. C1 WESTAT CORP,ROCKVILLE,MD 20850. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229. MARYLAND MED RES INST,BALTIMORE,MD. RP OBARZANEK, E (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,PREVENT DEMONSTRAT RES BRANCH,FED BLDG,ROOM 604,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HC-55023, HC-55025, HC-55024] NR 41 TC 139 Z9 141 U1 2 U2 7 PU AMER SOC CLINICAL NUTRITION 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 JUL PY 1994 VL 60 IS 1 BP 15 EP 22 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NW657 UT WOS:A1994NW65700004 PM 8017331 ER PT J AU HALLFRISCH, J SINGH, VN MULLER, DC BALDWIN, H BANNON, ME ANDRES, R AF HALLFRISCH, J SINGH, VN MULLER, DC BALDWIN, H BANNON, ME ANDRES, R TI HIGH PLASMA VITAMIN-C ASSOCIATED WITH HIGH PLASMA HDL-CHOLESTEROL AND HDL(2)-CHOLESTEROL SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE CHOLESTEROL; VITAMIN-C; LIPOPROTEINS; ATHEROGENESIS ID DENSITY-LIPOPROTEIN-CHOLESTEROL; ASCORBIC-ACID; SERUM-CHOLESTEROL; CARDIOVASCULAR-DISEASE; POPULATION; PRECIPITATION; ANTIOXIDANTS; QUANTITATION; RISK AB High plasma vitamin C may lower risk of cardiovascular disease as indicated by direct association with plasma high-density-lipoprotein (HDL) cholesterol and HDL(2) cholesterol. Plasma lipids and vitamin C were determined in 316 women and 511 men (aged 19-95 y). After adjustment for age, sex, obesity, and smoking, plasma vitamin C was directly associated with HDL- (P = 0.01) and HDL(2) cholesterol (P = 0.0002). When men and women with diseases that might affect lipids were excluded, associations between plasma vitamin C and HDL- and HDL(2) cholesterol persisted, though the relationships were strongest in older men. Comparisons of diets in a subset (n = 485) who completed 7-d diet records were made. Total fat, saturated fatty acids, energy from fat, and cholesterol intakes were not associated with plasma vitamin C. Mean intakes of vitamin C were well above recommended dietary allowances. These findings suggest that high plasma concentrations of vitamin C may lower atherogenic risk. C1 HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP HALLFRISCH, J (reprint author), USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,CARBOHYDRATE NUTR LAB,BLDG 307,ROOM 323,BELTSVILLE,MD 20705, USA. NR 33 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION 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 JUL PY 1994 VL 60 IS 1 BP 100 EP 105 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NW657 UT WOS:A1994NW65700017 PM 8017321 ER PT J AU HIJAZI, YM AXIOTIS, CA NAVARRO, S STEINBERG, SM HOROWITZ, ME TSOKOS, M AF HIJAZI, YM AXIOTIS, CA NAVARRO, S STEINBERG, SM HOROWITZ, ME TSOKOS, M TI IMMUNOHISTOCHEMICAL DETECTION OF P-GLYCOPROTEIN IN EWINGS-SARCOMA AND PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMORS BEFORE AND AFTER CHEMOTHERAPY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CHEMOTHERAPY; EWINGS SARCOMA; P-GLYCOPROTEIN; PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMORS ID MULTIDRUG-RESISTANCE GENE; BACTERIAL TRANSPORT PROTEINS; MAMMALIAN-CELL LINES; MONOCLONAL-ANTIBODIES; DIFFERENT EPITOPES; DRUG-RESISTANCE; HUMAN-TISSUES; EXPRESSION; LOCALIZATION; HOMOLOGY AB The authors evaluated P-glycoprotein expression in a total of 35 cases of Ewing's sarcoma and peripheral primitive neuroectodermal tumors (PNET). Fifteen cases had matched tumors before and after treatment. The 20 unmatched tumors included 14 pretreatment PNETs and Ewing's sarcomas and 6 posttreatment Ewing's sarcomas. Two antibodies, C219 and JSB-1, were used. Immunoreactivity was almost exclusively membranous. Variability in the number of positive cells and in staining intensity was noted within individual tumors. Among the 15 matched tumors, 7 were positive for P-glycoprotein before treatment; 6 of these remained positive after treatment. Four of the 8 that were negative for P-glycoprotein before treatment became positive after treatment. Of the unmatched tumors, 9 of 14 pretreatment and 3 of 6 posttreatment tumors were positive. When relapse-free survival time, based on the presence or absence of P-glycoprotein positivity in pretreatment tumor samples, was evaluated in this group, no significant difference was found (P-2 = .92); however, the numbers are too small to draw definitive conclusions. The high incidence of positive primary tumors suggests that P-glycoprotein expression is probably intrinsic in Ewing's sarcoma and PNET and not necessarily induced by therapy. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP HIJAZI, YM (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 45 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 1994 VL 102 IS 1 BP 61 EP 67 PG 7 WC Pathology SC Pathology GA NY416 UT WOS:A1994NY41600010 PM 7913576 ER PT J AU SLOAND, EM ALYONO, D KLEIN, HG CHANG, P YU, M LIGHTFOOT, FG KESSLER, C AF SLOAND, EM ALYONO, D KLEIN, HG CHANG, P YU, M LIGHTFOOT, FG KESSLER, C TI 1-DEAMINO-8-D-ARGININE VASOPRESSIN (DDAVP) INCREASES PLATELET MEMBRANE EXPRESSION OF GLYCOPROTEIN IB IN PATIENTS WITH DISORDERS OF PLATELET-FUNCTION AND AFTER CARDIOPULMONARY BYPASS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE PLATELET; GLYCOPROTEIN IB; CARDIOPULMONARY BYPASS; VASOPRESSIN ID VONWILLEBRAND-FACTOR INTERACTIONS; BERNARD-SOULIER SYNDROME; REDUCE BLOOD-LOSS; BLEEDING-TIME; DESMOPRESSIN ACETATE; CARDIAC-SURGERY; 1-DESAMINO-8-D-ARGININE VASOPRESSIN; MYELOPROLIFERATIVE DISORDERS; SURFACE GLYCOPROTEINS; ACTIVATED PLATELETS AB 1-deamino-8-D-Arginine vasopressin (DDAVP) shortens the bleeding time in some patients with platelet dysfunction and decreases blood loss in some cardiopulmonary bypass patients. We studied platelet membrane glycoproteins in patients with von Willebrand disease (vWD), disorders of platelet function, and in cardiopulmonary bypass patients after infusion of 0.3 mu g/kg of DDAVP. Platelets from 8 cardiopulmonary bypass patients, receiving DDAVP immediately after surgery, were compared to those of 14 patients not receiving DDAVP. We also studied 12 patients with vWD, and 8 patients with platelet dysfunction receiving DDAVP. Fixed platelets, stained with monoclonal fluorescein (FITC)-labeled antibodies directed against GPIb (CD42b antigen), GPIb/IX, GPIIb/IIIa (CD41a antigen), CD63 antigen (a platelet activation protein), and P-selectin (CD62 antigen) were studied by flow cytometry. Binding of CD42b monoclonal antibody (MoAb) and anti-GPIb/IX to platelets from both groups of bypass patients increased during the 18-20 hr after surgery, but the group receiving DDAVP showed the greater increase (P = 0.032). Platelets from patients receiving DDAVP for vWD or for platelet dysfunction, had increases in CD42b MoAb and anti-GPIb/IX binding (P < 0.01) that coincided with shortening of their bleeding time. No changes were seen in binding of other antibodies. When platelets from normal donors were incubated with DDAVP for 20 hr, there were increases in platelet surface CD42b MoAb binding, while immunogold-stained transmission electron micrographs of permeabilized platelets demonstrated decreases in cytoplasmic CD42b MoAb binding. DDAVP increases platelet membrane GPIb expression in a variety of patients and may account for improvement in hemostasis seen in some studies. Redistribution of GPIb from the cytoplasm to the membrane may account for this increased expression. (C) 1994 Wiley-Liss, Inc. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC. RP SLOAND, EM (reprint author), NHLBI,BLDG 31,RM 4A50,BETHESDA,MD 20892, USA. NR 52 TC 45 Z9 46 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 1994 VL 46 IS 3 BP 199 EP 207 DI 10.1002/ajh.2830460308 PG 9 WC Hematology SC Hematology GA NN209 UT WOS:A1994NN20900007 PM 8192149 ER PT J AU SHERER, DM ABULAFIA, O AF SHERER, DM ABULAFIA, O TI ULTRASONOGRAPHICALLY GUIDED SUBCLAVIAN VEIN CATHETERIZATION IN CRITICAL CARE OBSTETRICS AND GYNECOLOGIC ONCOLOGY - REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter ID PLACEMENT C1 MARSHALL UNIV,SCH MED,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,HUNTINGTON,WV 25703. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,NICHHD,DEPT OBSTET & GYNECOL,DIV INTRAMURAL,PERINATOL RE,3-PHC,WASHINGTON,DC 20007, USA. NR 5 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1994 VL 171 IS 1 BP 285 EP 287 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NZ068 UT WOS:A1994NZ06800070 ER PT J AU WIENER, L THEUT, S STEINBERG, SM RIEKERT, KA PIZZO, PA AF WIENER, L THEUT, S STEINBERG, SM RIEKERT, KA PIZZO, PA TI THE HIV-INFECTED CHILD - PARENTAL RESPONSES AND PSYCHOSOCIAL IMPLICATIONS SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Note ID DEPRESSION AB Four dimensions of psychological adaptation of 101 parents of HIV-infected children were examined Heightened anxiety, depression, and anticipatory grief were associated with child's age at diagnosis, parent's HIV status, and parent's relationship to the child. Parents at higher risk for psychological distress were identified, and an optimum time point for intervention is suggested. C1 NCI,CLIN ONCOL BRANCH,BETHESDA,MD 20892. NCI,INFECT DIS SECT,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,CHILDRENS NATL MED CTR,WASHINGTON,DC 20052. RP WIENER, L (reprint author), NCI,PEDIAT BRANCH,PEDIAT HIV,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 14 TC 22 Z9 22 U1 1 U2 2 PU AMER ORTHOPSYCHIATRIC ASSN PI NEW YORK PA 19 W 44TH ST, NEW YORK, NY 10036 SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JUL PY 1994 VL 64 IS 3 BP 485 EP 492 DI 10.1037/h0079539 PG 8 WC Psychiatry; Social Work SC Psychiatry; Social Work GA NX802 UT WOS:A1994NX80200016 PM 7977671 ER PT J AU BERTHEAU, P DELAROSA, A STEEG, PS MERINO, MJ AF BERTHEAU, P DELAROSA, A STEEG, PS MERINO, MJ TI NM23 PROTEIN IN NEOPLASTIC AND NONNEOPLASTIC THYROID TISSUES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID NUCLEOSIDE DIPHOSPHATE KINASE; LYMPH-NODE METASTASIS; HUMAN BREAST-CANCER; IMMUNOHISTOCHEMICAL ANALYSIS; PAPILLARY CARCINOMA; REDUCED EXPRESSION; TUMOR-METASTASIS; GOOD PROGNOSIS; MESSENGER-RNA; GENE AB The expression of nm23 gene products has been associated with a lower metastatic potential and better outcome in malignant tumors. We have used immunohistochemistry to study the expression of nm23 protein in thyroid tissues from 101 patients consisting of 78 malignant neoplasms, 13 adenomas, and 10 other benign conditions. Cytoplasmic staining for nm23 protein was identified in normal tissues and in most benign and malignant lesions and did not correlate with either histological type or clinical outcome. Nuclear staining was seen in 93% of normal tissues and in 29% of primary carcinomas of the thyroid and was associated with a longer disease-free survival (P = 0.03). Membranous staining was present in some tumors but absent in normal thyroid. In conclusion, nm23 protein has a combined pattern of distribution among subcellular compartments in thyroid tissues. Although there was no significant association between cytoplasmic or membranous expression and histological type of tumor or survival, nm23 nuclear expression may be a useful marker in assessing the evolution of thyroid tumors. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 37 TC 23 Z9 27 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1994 VL 145 IS 1 BP 26 EP 32 PG 7 WC Pathology SC Pathology GA NV861 UT WOS:A1994NV86100005 PM 8030752 ER PT J AU SMITH, MA KUTTY, RK RICHEY, PL YAN, SD STERN, D CHADER, GJ WIGGERT, B PETERSEN, RB PERRY, G AF SMITH, MA KUTTY, RK RICHEY, PL YAN, SD STERN, D CHADER, GJ WIGGERT, B PETERSEN, RB PERRY, G TI HEME OXYGENASE-1 IS ASSOCIATED WITH THE NEUROFIBRILLARY PATHOLOGY OF ALZHEIMERS-DISEASE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID PAIRED HELICAL FILAMENTS; HEAT-SHOCK; RAT-BRAIN; MESSENGER-RNA; SKIN FIBROBLASTS; APOLIPOPROTEIN-E; EXPRESSION; GLUTATHIONE; PROTEIN; GENE AB Heme oxygenase-1 is am important enzyme that degrades heme, a pro-oxidant, leading to the formation of antioxidant molecules. In this sherry we demonstrate by immunocytochemistry close association of heme oxygenase-1 with Alzheimer neurofibrillary pathology and with the neurofibrillary tangles found is progressive supranuclear palsy and subacute sclerosing panencephalitis. In Alzheimer's disease, using two different rabbit antisera against heme oxygenase-1 protein, we localized, using immunocytochemical methods, heme oxygenase-1 to neurofibrillary tangles, senile plaque neurites, granulovacuolar degeneration, and neuropil threads. Only light background staining was seen ill young controls and sporadic lesion-related immunoreactivity in age-matched controls. The increase in heme oxygenase-1 protein in association with the neurofibrillary pathology of Alzheimer's disease and other diseases characterized by neurofibrillary tangles supports the notion that the generation of free radicals and oxidative stress plays a role in the pathogenesis of neurofibrillary pathology. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,DEPT PHYSIOL,NEW YORK,NY. RP SMITH, MA (reprint author), CASE WESTERN RESERVE UNIV,INST PATHOL,DIV NEUROPATHOL,2085 ADELBERT RD,CLEVELAND,OH 44106, USA. RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009; Petersen, Robert/B-5075-2011 OI Perry, George/0000-0002-6547-0172; Petersen, Robert/0000-0002-3154-0072 FU NIA NIH HHS [AG07552, AG08992, AG09287] NR 43 TC 337 Z9 344 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1994 VL 145 IS 1 BP 42 EP 47 PG 6 WC Pathology SC Pathology GA NV861 UT WOS:A1994NV86100008 PM 8030754 ER PT J AU SHEIKHHAMAD, D GARCIAPEREZ, A FERRARIS, JD PETERS, EM BURG, MB AF SHEIKHHAMAD, D GARCIAPEREZ, A FERRARIS, JD PETERS, EM BURG, MB TI INDUCTION OF GENE-EXPRESSION BY HEAT-SHOCK VERSUS OSMOTIC-STRESS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE HEAT STRESS; ORGANIC OSMOLYTES; HEAT SHOCK PROTEIN 70; PROTEIN STABILIZATION ID RENAL MEDULLARY CELLS; ALPHA-B-CRYSTALLIN; ALDOSE REDUCTASE; INOSITOL COTRANSPORTER; ORGANIC OSMOLYTES; HSP70 EXPRESSION; MDCK CELLS; PROTEINS; CLONING; BETAINE AB Elevated temperature rapidly increases expression of genes for heat shock proteins (HSP), including HSP-70. The response is presumably triggered by denaturation of cell proteins and helps in their renaturation. Hypertonicity may also denature proteins, but the protective response, which is accumulation of compatible organic osmolytes [including betaine and inositol in Madin-Darby canine kidney (MDCK) cells], apparently differs and is slow. Recently, hypertonicity was found also to increase expression of HSP-70 in MDCK cells, a response proposed to provide protection until organic osmolytes can accumulate. Our purpose was to examine whether 1) a gene involved in accumulation of organic osmolytes also responds to heat stress and 2) whether accumulation of organic osmolytes affects expression of HSP-70. We find that 1) the betaine transporter mRNA, which is greatly increased by hypertonicity (515 vs. 315 mosmol), is unaffected by high temperature (42 degrees C vs. 37 degrees C); 2) hypertonicity-induced increases in HSP-70 and betaine transporter mRNA are much greater when the medium (and cell) contain no betaine and no inositol than when high concentrations of these are present; and 3) high betaine greatly inhibits the increase in HSP-70 mRNA at high temperature. We conclude the following. 1) Although heat shock and betaine transporter genes both respond to hypertonicity, the betaine transporter is not a HSP. 2) Accumulation of organic osmolytes attenuates the HSP-70 response to hypertonicity, as it might if the HSP-70 expression were a temporizing response. 3) Betaine inhibits HSP-70 response to elevated temperature, presumably by its known effect of stabilizing proteins. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 40 TC 96 Z9 96 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP F28 EP F34 PN 2 PG 7 WC Physiology SC Physiology GA NY985 UT WOS:A1994NY98500103 PM 8048561 ER PT J AU LAUGHLIN, MR TAYLOR, J CHESNICK, AS BALABAN, RS AF LAUGHLIN, MR TAYLOR, J CHESNICK, AS BALABAN, RS TI NONGLUCOSE SUBSTRATES INCREASE GLYCOGEN-SYNTHESIS IN-VIVO IN DOG HEART SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CARBON-13-NUCLEAR MAGNETIC RESONANCE; LACTATE; PYRUVATE; BETA-HYDROXYBUTYRATE ID MYOCARDIAL-METABOLISM; INTRACELLULAR PH; RAT-HEART; INVIVO; EXERCISE; SYNTHASE; GLYCOLYSIS; LACTATE; INSULIN; STIMULATION AB The effects of circulating nonglucose substrates on insulin-stimulated cardiac glycogen synthesis were studied in the dog heart in vivo using C-13-nuclear magnetic resonance (-NMR) and arteriovenous difference techniques. [1-C-13]glycogen was monitored in hearts during an intravenous infusion of 20 mU/min insulin and glucose while [1-C-13]glucose (10 mg/min) was infused into the left anterior descending coronary artery. When 1 mmol/ min of lactate, pyruvate, or P-hydroxybutyrate was added to the venous infusion, the measured rate of glycogen synthesis was increased, on average, sixfold. It was not increased further after a subsequent 10-min infusion of 5 mu g/min epinephrine. Lactate extraction increased from 0.18 +/- 0.05 to 0.62 +/- 0.11 mu mol . min(-1) . g wet wt(-1) during lactate infusion, whereas glucose extraction did not change significantly (0.15 +/- 0.05 mu mol . min(-1) . g wet wt(-1) at 45 min of insulin and glucose infusion to 0.09 +/- 0.02 mu mol . min(-1) g wet wt(-1) at 45 min of the lactate infusion). Therefore, the uptake and oxidation of circulating nonglucose substrates redirects the fate of extracted glucose from glycolysis to glycogen synthesis in the dog heart in vivo. RP LAUGHLIN, MR (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 1,RM R3-07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 10 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP H217 EP H223 PN 2 PG 7 WC Physiology SC Physiology GA NY985 UT WOS:A1994NY98500028 ER PT J AU PEDEN, DB DAILEY, L DEGRAFF, W MITCHELL, JB LEE, JG KALINER, MA HOHMAN, RJ AF PEDEN, DB DAILEY, L DEGRAFF, W MITCHELL, JB LEE, JG KALINER, MA HOHMAN, RJ TI HYDROGEN-PEROXIDE EFFECTS ON RAT MAST-CELL FUNCTION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE OXIDANT; ALLERGY; INFLAMMATION ID DEPENDENT CHEMI-LUMINESCENCE; BRONCHIAL RESPONSIVENESS; BRONCHOALVEOLAR LAVAGE; NEUTRAL ENDOPEPTIDASE; AIRWAY RESPONSIVENESS; PULMONARY-FUNCTION; HISTAMINE-RELEASE; CIGARETTE-SMOKE; SUBSTANCE-P; DNA DAMAGE AB Oxidant exposure of the airway mucosa may play a significant role in the pathophysiology of asthma and allergic rhinitis. Mast cells play an important role in asthma, and oxidant exposure has been reported to cause direct mast cell degranulation as well as augment immunoglobulin E (IgE)-mediated responses in vivo. H2O2 is an oxidant generated by inflammatory cells and by the interaction of ozone with lipids or aqueous solutions. In this study, the RBL-2H3 mast cell line was used to investigate the ability of H2O2 to induce mast cell responses as well as to effect mast cell responses to IgE and the calcium ionophore A23187. Although cytotoxicity of RBL-2H3 cells at the membrane level was not observed with any concentration of H2O2, DNA damage resulted from exposure to 0.2 and 2.0 mM H2O2, and cell proliferation was inhibited by 0.075-0.2 mM H2O2. RBL cell prostaglandin D-2 generation was enhanced after 60- and 120-min exposure to 0.2-20 mM H2O2. Direct serotonin release required 120-min exposures to 2.0 mM and 60-min exposures to 20 mM H2O2. However, degranulation responses induced by either IgE or A23178 were diminished after exposure to 0.2-2.0 mM H2O2. Lesser amounts (0.005-0.02 mM) had no effect on mast cell function. In summary, H2O2-induced responses of RBL cells, as well as modification of responses to IgE and A23187, occurred only at high concentrations of H2O2, which also induced both intracellular damage and inhibition of cell proliferation. Concentrations of H2O2 more likely to be physiologically relevant had no effect on mast cell responses or cytotoxcity. Thus oxidant-induced changes of in vivo mast cell-mediated responses are likely due to their effects on adjacent tissues, which either interact with mast cells or are targets of mast cell-derived mediators. C1 UNIV N CAROLINA,SCH MED,DEPT PEDIAT,DIV PULM MED,ALLERGY SERV,CHAPEL HILL,NC 27599. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,INST ASTHMA & ALLERGY,WASHINGTON,DC 20008. ONCOR INC,GAITHERSBURG,MD 20877. RP PEDEN, DB (reprint author), UNIV N CAROLINA,SCH MED,CTR ENVIRONM MED & LUNG BIOL,CB 7310,MED BLDG B,CHAPEL HILL,NC 27599, USA. NR 44 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP L85 EP L93 PN 1 PG 9 WC Physiology SC Physiology GA NY984 UT WOS:A1994NY98400088 PM 8048546 ER PT J AU MILLER, DS BARNES, DM PRITCHARD, JB AF MILLER, DS BARNES, DM PRITCHARD, JB TI CONFOCAL MICROSCOPIC ANALYSIS OF FLUORESCEIN COMPARTMENTATION WITHIN CRAB URINARY-BLADDER CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE KIDNEY; P-AMINOHIPPURIC ACID; NOCODAZOLE; INTRACELLULAR VESICLES; MICROTUBULES; ORGANIC ANION SECRETION; TRANSCYTOSIS ID CANCER-BOREALIS; ORGANIC ANION; PROXIMAL TUBULES; TRANSPORT; SECRETION; SODIUM; IRRORATUS AB Fluorescein (FL), a fluorescent organic anion, is compartmentalized in cells of organic anion-secreting epithelia, e.g., OK cells, teleost proximal tubule, and crab (Cancer borealis) urinary bladder, a proximal tubule analogue. To further examine the processes involved, FL uptake and distribution were studied in C. borealis urinary bladder cells using epifluorescence and laser confocal microscopy combined with video-image analysis. Intracellular FL was about evenly split between diffuse and punctate compartments after in vitro or in vivo loading. Treatments that affected FL transport into cells (incubation with p-aminohippuric acid or glutarate) altered the FL content of both compartments. However, nocodazole, a microtubule inhibitor, did not affect diffuse FL but significantly reduced punctate FL. Finally, confocal analysis indicated that individual sites of punctate FL accumulation moved in the secretory direction at 0.83 mu m/min. Nocodazole nearly abolished this movement and significantly reduced transepithelial organic anion secretion. Thus, in crab urinary bladder, a substantial fraction of total cellular FL is sequestered in vesicles, and these vesicles move in the secretory direction, by a microtubule-dependent process. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,RES TRIANGLE PK,NC 27709. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. RP MILLER, DS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INTRACELLULAR REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP R16 EP R25 PN 2 PG 10 WC Physiology SC Physiology GA NY985 UT WOS:A1994NY98500054 PM 8048619 ER PT J AU AMMERMAN, A CAGGIULA, A ELMER, PJ KRISETHERTON, P KEYSERLING, T LEWIS, C LUEPKER, R PEARSON, T SCHUCKER, B SHANNON, B SIMPSON, RJ WATSON, J AF AMMERMAN, A CAGGIULA, A ELMER, PJ KRISETHERTON, P KEYSERLING, T LEWIS, C LUEPKER, R PEARSON, T SCHUCKER, B SHANNON, B SIMPSON, RJ WATSON, J TI PUTTING MEDICAL-PRACTICE GUIDELINES INTO PRACTICE - THE CHOLESTEROL MODEL SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB As more and more medical practice guidelines are developed in the United States, commensurate evaluation efforts should assess their impact on professional practice and patient outcomes. We describe an ongoing research program designed to develop and test practice models for applying the 1988 Adult Treatment Panel Guidelines for the clinical management of high blood cholesterol. Four studies are evaluating different models to assist nonacademic community practices in the detection, evaluation, and treatment of high blood cholesterol. We have designed randomized controlled trials set in solo and small-group primary care practices of family or general practitioners and internists situated in rural, suburban, and urban settings. Patients include adult men and women who represent diverse socioeconomic and ethnic backgrounds. We are measuring rates of cholesterol screening; dietary and drug treatment and follow-up; changes in dietary intake and compliance with drug therapy; changes in quality of life and cost of intervention; and reduction in cholesterol level. Scheduled for completion in 1994, this program will provide insights into practical and effective methods of lipid management. It serves as a model for studying the application of health guidelines in the context of nonacademic primary care practices serving diverse patient populations. C1 NHLBI,DIV HEART & VASC DIS,LIPID METAB ATHEROGENESIS BRANCH,FED BLDG,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 44160, HL 44141, HL 44157] NR 0 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1994 VL 10 IS 4 BP 209 EP 216 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PH877 UT WOS:A1994PH87700005 PM 7803063 ER PT J AU GOHAGAN, JK KRAMER, BS GREENWALD, P AF GOHAGAN, JK KRAMER, BS GREENWALD, P TI SCREENING FOR PROSTATE-CANCER SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material RP GOHAGAN, JK (reprint author), NCI,EARLY DETECT BRANCH,ROCKVILLE,MD 20852, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1994 VL 10 IS 4 BP 245 EP 246 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PH877 UT WOS:A1994PH87700012 PM 7528519 ER PT J AU MILBY, JB HOHMANN, AA GENTILE, M HUGGINS, N SIMS, MK MCLELLAN, AT WOODY, G HAAS, N AF MILBY, JB HOHMANN, AA GENTILE, M HUGGINS, N SIMS, MK MCLELLAN, AT WOODY, G HAAS, N TI METHADONE-MAINTENANCE OUTCOME AS A FUNCTION OF DETOXIFICATION PHOBIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FEAR; RELIABILITY; ABSTINENCE AB Objective: Methadone maintenance outcome as a function of detoxification phobia was examined. Method: Opiate addicts (N=271) in a 1983 random sample of methadone maintenance patients from three diverse populations were studied. Subjects from an individually assessed follow-up sample (N=102) were compared on detoxification phobia. Logistic regression analysis yielded best predictors of the phobia. Results: Phobic patients were more likely to be white, female, and abstinent; to have had fewer detoxification attempts and longer periods on maintenance; to show persistence of the phobia; to meet diagnostic criteria for depressive or anxiety disorders; and to have Addiction Severity Index scores above the 75th percentile for psychological problems. Conclusions: Detoxification phobia has a complex relationship to methadone maintenance outcome. It is associated with greater abstinence for patients in methadone maintenance treatment. However, for rehabilitated phobic patients it presents a barrier to successful detoxification and a drug-free adjustment that is often associated with other psychopathology but could be ameliorated by targeted assessment and treatment. C1 UNIV ALABAMA,BIRMINGHAM,AL. NIMH,PHILADELPHIA,PA. VET ADM MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. VET ADM MED CTR,SEPULVEDA,CA 91343. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP MILBY, JB (reprint author), VET ADM MED CTR,PSYCHOL SERV 116B,700 19TH ST S,BIRMINGHAM,AL 35233, USA. FU NIDA NIH HHS [DA-05502] NR 21 TC 12 Z9 12 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 JUL PY 1994 VL 151 IS 7 BP 1031 EP 1037 PG 7 WC Psychiatry SC Psychiatry GA NU656 UT WOS:A1994NU65600014 PM 8010360 ER PT J AU HITRI, A CASANOVA, MF KLEINMAN, JE WYATT, RJ AF HITRI, A CASANOVA, MF KLEINMAN, JE WYATT, RJ TI FEWER DOPAMINE TRANSPORTER RECEPTORS IN THE PREFRONTAL CORTEX OF COCAINE USERS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID HUMAN-BRAIN; RAT-BRAIN; BINDING AB The authors investigated dopamine transporter receptor binding in the post-mortem prefrontal cortex of 13 subjects with histories of cocaine use who had positive blood screens for cocaine at autopsy and 13 comparison subjects with no history of cocaine use and negative blood screens for cocaine at autopsy. Synaptosomes from Pulverized prefrontal cortex were assayed with [H-3]GBR 12935 for dopamine transporter receptor. There was a 38% decrease in number of binding sites but no change in affinity constants in the cocaine users. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIATRY BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP HITRI, A (reprint author), VET ADM MED CTR,NIDA,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 16 TC 40 Z9 40 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1994 VL 151 IS 7 BP 1074 EP 1076 PG 3 WC Psychiatry SC Psychiatry GA NU656 UT WOS:A1994NU65600022 PM 8010366 ER PT J AU GOEDERT, JJ COTE, TR AF GOEDERT, JJ COTE, TR TI PUBLIC-HEALTH INTERVENTIONS TO REDUCE PEDIATRIC AIDS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID HIV-1 INFECTION; UNITED-STATES; PREVENTION; WOMEN RP GOEDERT, JJ (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,AIDS & CANC SECT,6130 EXECUT BLVD,SUITE 434,ROCKVILLE,MD 20852, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1994 VL 84 IS 7 BP 1065 EP 1066 DI 10.2105/AJPH.84.7.1065 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PB870 UT WOS:A1994PB87000001 PM 8017523 ER PT J AU BIRRER, P MCELVANEY, NG RUDEBERG, A SOMMER, CW LIECHTIGALLATI, S KRAEMER, R HUBBARD, R CRYSTAL, RG AF BIRRER, P MCELVANEY, NG RUDEBERG, A SOMMER, CW LIECHTIGALLATI, S KRAEMER, R HUBBARD, R CRYSTAL, RG TI PROTEASE-ANTIPROTEASE IMBALANCE IN THE LUNGS OF CHILDREN WITH CYSTIC-FIBROSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID EPITHELIAL LINING FLUID; LOWER RESPIRATORY-TRACT; PSEUDOMONAS-AERUGINOSA; NEUTROPHIL ELASTASE; CHRONIC INFLAMMATION; UNKNOWN CAUSE; CELL LINE; GENE; IDENTIFICATION; EXPRESSION AB Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/mu l ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. UNIV BERN,INSELSPITAL,CHILDRENS CLIN,CH-3010 BERN,SWITZERLAND. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY. RI McElvaney, Noel/A-6809-2010 NR 43 TC 269 Z9 275 U1 0 U2 6 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 JUL PY 1994 VL 150 IS 1 BP 207 EP 213 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NW659 UT WOS:A1994NW65900035 PM 7912987 ER PT J AU CRAPO, J MALIK, AB MOSSMAN, B GAIL, DB AF CRAPO, J MALIK, AB MOSSMAN, B GAIL, DB TI IN-VIVO CELL BIOLOGY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID SUPEROXIDE-DISMUTASE; SURFACTANT PROTEIN; MICROSCOPY; EXPRESSION; LUNG C1 NHLBI, DIV LUNG DIS, BETHESDA, MD 20892 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1994 VL 150 IS 1 BP 282 EP 286 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NW659 UT WOS:A1994NW65900048 PM 8025765 ER PT J AU POWELL, FC SPOONER, KM SHAWKER, TH PREMKUMAR, A THAKORE, KN VOGEL, SE KOVACS, JA MASUR, H FEUERSTEIN, IM AF POWELL, FC SPOONER, KM SHAWKER, TH PREMKUMAR, A THAKORE, KN VOGEL, SE KOVACS, JA MASUR, H FEUERSTEIN, IM TI SYMPTOMATIC INTERLEUKIN-2-INDUCED CHOLECYSTOPATHY IN PATIENTS WITH HIV-INFECTION SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID KILLER-CELL THERAPY; GALLBLADDER WALL; RECOMBINANT INTERLEUKIN-2; CHOLECYSTITIS; ABNORMALITIES; AIDS AB OBJECTIVE. This study reports the clinical and radiologic findings in seven patients infected with HIV who had 10 consecutive episodes of symptomatic cholecystopathy induced by infusion of interleukin-2. SUBJECTS AND METHODS. Ten episodes of right upper quadrant pain associated with gallbladder wall thickening were seen in seven of 29 HIV-infected patients who received IV interleukin-2. Patients received 6-18 million IU/day of continuous interleukin-2 infusion for 5 days. Patients with right upper quadrant pain underwent sonographic examinations, which were interpreted prospectively. Medical records and previous sonographic studies were reviewed retrospectively. Follow-up was obtained through outpatient visits and sonography. RESULTS. Right upper quadrant pain during these 10 episodes of cholecystopathy usually developed 4-5 days after starting infusion of interleukin-2. Sonography during that time showed gallbladder wall thickening (mean thickness, 12.4 mm; range, 5-18 mm) and a wide variety of sonographic appearances. Tenderness during sonography was focal in six episodes, diffuse in one, and absent in three. Sludge was identified in one episode; calculi were not seen, Findings on radionuclide biliary scans were normal in three cases. Symptoms abated rapidly in every case after infusion of interleukin-a was reduced or stopped. No surgery was necessary. When treatment was repeated, three patients had recurrent episodes, with clinical courses and sonographic aberrations showing little variance from the initial episodes, Follow-up sonography in three episodes showed a maximal thickness of the gallbladder wall of 4 mm, No patient had a history or laboratory evidence of intrinsic biliary disease. CONCLUSION, Symptomatic thickening of the gallbladder wall during infusion of interleukin-2 can exactly mimic other forms of acalculous cholecystitis, except that when associated with interleukin-2 the thickening is rapidly reversible and surgery is not required. Radionuclide scans can be useful in clinical decision making. The process appears to be benign, and cessation of interleukin-2 therapy, along with close clinical observation, appears to be the appropriate treatment. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD 20850. UNIFORMED SERV UNIV HLTH SCI,DEPT RADIOL,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. NIAID,BETHESDA,MD. NR 21 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1994 VL 163 IS 1 BP 117 EP 121 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE286 UT WOS:A1994QE28600024 PM 8010196 ER PT J AU DARAWSHE, S MINTON, AP AF DARAWSHE, S MINTON, AP TI QUANTITATIVE CHARACTERIZATION OF MACROMOLECULAR ASSOCIATIONS IN SOLUTION VIA REAL-TIME AND POSTCENTRIFUGATION MEASUREMENTS OF SEDIMENTATION EQUILIBRIUM - A COMPARISON SO ANALYTICAL BIOCHEMISTRY LA English DT Review RP DARAWSHE, S (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,PHYS BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 13 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL PY 1994 VL 220 IS 1 BP 1 EP 4 DI 10.1006/abio.1994.1289 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NV049 UT WOS:A1994NV04900001 PM 7978232 ER PT J AU MOODY, EJ HARRIS, B HOEHNER, P SKOLNICK, P AF MOODY, EJ HARRIS, B HOEHNER, P SKOLNICK, P TI INHIBITION OF [H-3] ISRADIPINE BINDING TO L-TYPE CALCIUM CHANNELS BY THE OPTICAL ISOMERS OF ISOFLURANE - LACK OF STEREOSPECIFICITY SO ANESTHESIOLOGY LA English DT Article DE ANESTHETICS, VOLATILE, CA2+ CHANNELS ISOFLURANE ISRADIPINE MECHANISM OF ACTION STEREOISOMERS ID RAT-BRAIN; VOLATILE ANESTHETICS; BLOCKER BINDING; HALOTHANE; SARCOLEMMA; MEMBRANES; COMPLEX; SITES AB Background: The dose-dependent myocardial depression of volatile general anesthetics such as isoflurane has been linked to blockade of L-type Ca2+ channels. The effects of (+)- and (-)-isoflurane on the inhibition of [H-3]isradipine binding to L-type Ca2+ channels in membranes prepared from mouse heart were examined. In addition, because there is a stereospecific effect of these isomers on sleep time in mice, the potential contribution of L-type Ca2+ channels to isoflurane-induced sleep was assessed by determining whether a similar stereoselectivity would be manifested at these sites in cerebral cortical membranes. Methods: The effects of isoflurane stereoisomers on the binding of an L-type Ca2+ channel ligand ([H-3]isradipine) were studied in cardiac and brain cortical membranes. Their potencies and effects on the K-d and B-max of [H-3]isradipine were measured. Results: Pharmacologically relevant concentrations of (+)- and (-)-isoflurane inhibited [H-3]isradipine binding. The IC50 values for (+)-isoflurane were 0.48 +/- 0.02% and 0.40 +/- 0.01% in heart and brain membranes, respectively. The values for (-)-isoflurane were not significantly different from the respective values for the (+)-isomer. Saturation analysis demonstrated (+)- and (-)-isoflurane inhibited [H-3]isradipine binding by significantly reducing B-max and increasing K-d, but there were no significant differences between these isomers in either tissue. Conclusions: The stereoisomers of isoflurane are equipotent as inhibitors of [H-3]isradipine binding to L-type Ca2+ channels. This lack of stereoselectivity between (+)- and (-)-isoflurane indicates that the [H-3]isradipine site on L-type Ca2+ channels in brain does not contribute to the differences in isoflurane-induced sleep time reported for these stereoisomers. Taken with a lack of stereoselectivity at L-type Ca2+ channels in heart, an optically resolved isomer of isoflurane may have clinical advantages compared to the current racemic mixture. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,DIV CARDIAC ANESTHESIA,BALTIMORE,MD 21205. RP MOODY, EJ (reprint author), NIH,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 19 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1994 VL 81 IS 1 BP 124 EP 128 DI 10.1097/00000542-199407000-00018 PG 5 WC Anesthesiology SC Anesthesiology GA NW235 UT WOS:A1994NW23500018 PM 8042780 ER PT J AU CSAKO, G AF CSAKO, G TI HIGH ANALYTE CONCENTRATIONS IN AIRFUGED SPECIMENS SO ANNALS OF CLINICAL BIOCHEMISTRY LA English DT Letter RP CSAKO, G (reprint author), NIH,WG MAGNUSON CLIN CTR,CLIN DEPT PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0004-5632 J9 ANN CLIN BIOCHEM JI Ann. Clin. Biochem. PD JUL PY 1994 VL 31 BP 389 EP 390 PN 4 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PA398 UT WOS:A1994PA39800018 PM 7979110 ER PT J AU PASS, HI SINDELAR, WF KINSELLA, TJ DELUCA, AM BARNES, M KURTZMAN, S HOEKSTRA, H TOCHNER, Z ROTH, J GLATSTEIN, E AF PASS, HI SINDELAR, WF KINSELLA, TJ DELUCA, AM BARNES, M KURTZMAN, S HOEKSTRA, H TOCHNER, Z ROTH, J GLATSTEIN, E TI DELIVERY OF INTRAOPERATIVE RADIATION-THERAPY AFTER PNEUMONECTOMY - EXPERIMENTAL-OBSERVATIONS AND EARLY CLINICAL-RESULTS SO ANNALS OF THORACIC SURGERY LA English DT Article ID LUNG-CANCER; RADIOTHERAPY AB Intraoperative radiation therapy (IORT) is capable of delivering high doses of radiation to mediastinal structures while sparing lung parenchyma, heart, and other locoregional tissues. A canine model of pulmonary resection and IORT was investigated by performing a pneumonectomy in 15 adult foxhounds followed by 0 cGy, 2,000 cGy, 3,000 cGy, or 4,000 cGy. No clinical complications developed in 4 animals in the 2,000-cGy group. However, 2 of the 8 animals given a high dose died of esophageal hemorrhage or carinal necrosis. Esophagitis occurred in 10 of 12 animals, and none of the animals experienced bronchial stump dehiscence. In a limited Phase I protocol, 4 patients with non-small cell lung cancer were treated with resection and 2,500 cGy of IORT to two separate ports encompassing the superior and inferior mediastinum. Two patients experienced life-threatening bronchopleural fistulas, and 2 patients died as a consequence of esophageal problems. One patient had recurrence with brain metastases, and the 1 long-term survivor is free from disease. As opposed to the animal model of thoracic IORT, the clinical study demonstrated major toxicity with respiratory and esophageal morbidity. The therapeutic usefulness of thoracic IORT in the management of lung cancer must be questioned in view of this small but consistent series of patients. Further carefully designed clinical studies using lower doses of IORT are needed. RP PASS, HI (reprint author), NCI,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1994 VL 58 IS 1 BP 269 EP 270 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NY765 UT WOS:A1994NY76500071 PM 8037548 ER PT J AU STRETCHER, BN PESCE, AJ FRAME, PT STEIN, DS AF STRETCHER, BN PESCE, AJ FRAME, PT STEIN, DS TI PHARMACOKINETICS OF ZIDOVUDINE PHOSPHORYLATION IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AIDS-RELATED COMPLEX; CONTROLLED TRIAL; 3'-AZIDO-3'-DEOXYTHYMIDINE; THERAPY; DNA; AZT AB As part of an effort towards optimization of dosing of zidovudine (ZDV), formation and elimination of total phosphorylated ZDV (ZDVPt) in peripheral blood mononuclear cells were examined in 21 asymptomatic human immunodeficiency virus-infected patients during their first 24 weeks of therapy (AIDS Clinical Trials Group Protocol 161). Intracellular concentrations of ZDVPt were measured with a previously described and validated radioimmunoassay technique. Although ZDV phosphorylation occurred readily upon initiation of therapy, it declined with time; the area under the concentration-time curve (AUC) at week 4 (mean +/- standard deviation, 3.41 +/- 0.93 pmol.h/10(6) cells) was significantly greater than that at week 24 (2.19 +/- 1.10 pmol.h/10(6) cells). Plasma ZDV AUC did not change with time and did not correlate with ZDVPt AUC. In dose-response experiments (20 to 100 mg orally), phosphorylation did not proportionally increase with increasing plasma ZDV concentrations. Similarly, compared with a single dose, two doses of ZDV over an 8-h period resulted in little ZDVPt increase in cells relative to increases in plasma ZDV concentrations. The half-life of intracellular ZDVPt was twice that of plasma ZDV (4 versus 2 h), suggesting that an every-8-h dosing regimen is justifiable. These findings suggest that metabolism of ZDV to its active intracellular forms may be saturable in some patients, is poorly correlated with plasma concentrations, and diminishes over time. These findings have implications for future development and management of anti-human immunodeficiency virus nucleoside therapy. C1 UNIV CINCINNATI,COLL MED,DEPT PATHOL & LAB MED,CINCINNATI,OH 45267. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,CINCINNATI,OH 45267. NIAID,DIV AIDS,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-25897] NR 27 TC 62 Z9 62 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1994 VL 38 IS 7 BP 1541 EP 1547 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NU598 UT WOS:A1994NU59800018 PM 7979286 ER PT J AU FALLOON, J LAVELLE, J OGATAARAKAKI, D BYRNE, A GRAZIANI, A MORGAN, A AMANTEA, MA OWNBY, K POLIS, M DAVEY, RT KOVACS, JA LANE, HC MASUR, H MACGREGOR, RR AF FALLOON, J LAVELLE, J OGATAARAKAKI, D BYRNE, A GRAZIANI, A MORGAN, A AMANTEA, MA OWNBY, K POLIS, M DAVEY, RT KOVACS, JA LANE, HC MASUR, H MACGREGOR, RR TI PHARMACOKINETICS AND SAFETY OF WEEKLY DAPSONE AND DAPSONE PLUS PYRIMETHAMINE FOR PREVENTION OF PNEUMOCYSTIS PNEUMONIA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CARINII PNEUMONIA; AEROSOLIZED PENTAMIDINE; PRIMARY PROPHYLAXIS; AIDS; SULFAMETHOXAZOLE; TOXOPLASMOSIS; COTRIMOXAZOLE; TRIMETHOPRIM; FAILURE AB The safety and pharmacokinetics of weekly dapsone and weekly dapsone plus pyrimethamine were examined in adult patients with human immunodeficiency virus infection who were at risk for pneumocystis pneumonia because of a prior episode or a CD4(+) T-cell count less than 250 cells per mm(3). Groups of patients received 100, 200, and 300 mg of dapsone as a single weekly dose. The maximum tolerated dose of weekly dapsone was established as 200 mg per week in patients receiving at least 500 mg of zidovudine concomitantly. This dose of dapsone was then found to be well tolerated when combined with pyrimethamine at 25 mg. Further patients were randomized to dapsone at 200 mg or dapsone at 200 mg plus pyrimethamine at 25 mg once weekly. Twenty-six patients each were followed for a median of 33 weeks on dapsone alone and 45 weeks on the combination. Seven patients in each group withdrew because of toxicity. Five patients receiving dapsone developed documented pneumocystis pneumonia, while four and two patients receiving dapsone plus pyrimethamine developed documented and presumptive pneumocystis pneumonia, respectively. To evaluate the tolerability of a higher dose of pyrimethamine, 11 patients had their regimen changed to dapsone at 200 mg plus pyrimethamine at 75 mg, which was well tolerated by 10 of the patients for a median period of 11 weeks. The pharmacokinetics of dapsone and pyrimethamine were examined by using a population pharmacokinetic model. Decreases in the apparent volume of the peripheral compartment were observed when multiple-dose regimens of dapsone were compared with single-dose dapsone and when multiple-dose regimens of dapsone with pyrimethamine were compared with multiple-dose dapsone alone. When administered weekly, dapsone at 200 mg and dapsone at 200 mg with pyrimethamine at 25 mg are both well-tolerated regimens. This preliminary study suggests that the efficacy of these regimens in preventing pneumocystis pneumonia, however, may be less than that of trimethoprim-sulfamethoxazole. C1 NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RP FALLOON, J (reprint author), NIAID,LIR,BLDG 10,RM 11C-103,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 29 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1994 VL 38 IS 7 BP 1580 EP 1587 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NU598 UT WOS:A1994NU59800024 PM 7979291 ER PT J AU POLI, G BISWAS, P FAUCI, AS AF POLI, G BISWAS, P FAUCI, AS TI INTERFERONS IN THE PATHOGENESIS AND TREATMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO ANTIVIRAL RESEARCH LA English DT Article DE INTERFERON; HIV; ANTIRETROVIRAL EFFECT; PATHOGENESIS ID TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; AIDS-RELATED COMPLEX; GAMMA-INTERFERON; HIV-INFECTION; FACTOR-ALPHA; HTLV-III; PROMONOCYTIC CELLS; BETA-INTERFERON; IFN-ALPHA AB There still remains several unanswered questions concerning the pathogenesis of human immunodeficiency virus (HIV) infection. Interferons (IFNs), as well as other cytokines, are both dysregulated in HIV infection and serve as effector molecules that modulate the replicative capacity of HIV. Acid-labile IFN-alpha, an aberrant form of interferon earlier described in certain autoimmune diseases, has been detected in HIV-infected individuals. Conversely, a deficient expression of IFN-alpha may occur usually associated with HIV disease. Although conflicting findings have been reported on whether IFN-gamma, a product of activated T and natural killer (NK) cells, is elevated in the peripheral blood (PB) compartment, high levels of its expression have been observed in the germinal centers of the lymph nodes during HIV disease. IFN-alpha and IFN-beta have shown potent anti-retroviral effects in several in vitro systems of both acute and chronic HIV infection. These findings have served as the basis of the rationale for their therapeutic application, resulting in some positive effects at least in those patients with relatively high CD4(+) T cell counts and healthy immune functions. Furthermore, IFN-alpha has shown important therapeutic effects on HIV-associated Kaposi's sarcoma (KS). Both suppressive and inductive effects on HIV replication in vitro have been described for IFN-gamma, whereas no clear clinical benefits have been reported following its administration to HIV-infected individuals. In conclusion, IFNs are involved in several pathogenic aspects of HIV infection and AIDS, and certain IFNs may serve as important tools to limit the spread of the virus and the progression of disease. C1 SAN RAFFAELE SCI INST,DIBIT,AIDS IMMUNOPATHOGENESIS UNIT,MILAN,ITALY. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 99 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 1994 VL 24 IS 2-3 BP 221 EP 233 DI 10.1016/0166-3542(94)90069-8 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA NX600 UT WOS:A1994NX60000013 PM 7526793 ER PT J AU LEE, BR LECCHI, P PANNELL, L JAFFE, H PETERKOFSKY, A AF LEE, BR LECCHI, P PANNELL, L JAFFE, H PETERKOFSKY, A TI IDENTIFICATION OF THE N-TERMINAL DOMAIN OF ENZYME-I OF THE ESCHERICHIA-COLI PHOSPHOENOLPYRUVATE-SUGAR PHOSPHOTRANSFERASE SYSTEM PRODUCED BY PROTEOLYTIC DIGESTION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID TRANSPORT AB The phosphoenolpyruvate:sugar phosphotransferase system of bacteria plays an important role in the concomitant uptake and phosphorylation of numerous sugars. The first protein in the pathway of phosphotransfer of the phosphoenolpyruvate:sugar phosphotransferase system is Enzyme I. It has been shown that a stable N-terminal domain can be produced by treatment of the purified protein with various proteolytic enzymes. We show here that the region from glutamate-252 to leucine-264 is accessible to proteolysis resulting in N-terminal cores ranging from M(r) 27521 to 28799. (C) 1994 Academic Press, Inc. C1 NIH,BETHESDA,MD 20892. NR 11 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1994 VL 312 IS 1 BP 121 EP 124 DI 10.1006/abbi.1994.1289 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX107 UT WOS:A1994NX10700017 PM 8031118 ER PT J AU DUNCAN, T KUTTY, G CHADER, GJ WIGGERT, B AF DUNCAN, T KUTTY, G CHADER, GJ WIGGERT, B TI A GLYCOPROTEIN BINDING RETINOIDS AND FATTY-ACIDS IS PRESENT IN DROSOPHILA SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID PROTEIN IRBP; RHODOPSIN; PURIFICATION; PIGMENT AB In the search for a possible Drosophila melanogaster homolog of interphotoreceptor retinoid-binding protein (IRBP), a similar to 140-kDa retinoid- and fatty acid-binding glycoprotein found in vertebrates, the 110,000 g supernatant fraction prepared from homogenates of fly heads was analyzed for the presence of proteins capable of binding radiolabeled retinol and palmitic acid. A soluble protein, which binds concanavalin A and has a retention time on size-exclusion high-performance liquid chromatography identical to that of purified bovine IRBP, was identified as binding both ligands. As assessed by fluorescence titration, the protein fraction obtained by concanavalin A-Sepharose affinity chromatography and size-exclusion chromatography of fly head supernatant had apparent dissociation constants of 2.9 X 10(-7) +/- 0.6 M for all-trans retinol, with the number (n) of independent ligand binding sites per protein molecule = 2, and 3.5 X 10(-7) +/- 0.1 M for 16-[9-anthroyloxy] palmitic acid with n = 7. High-performance liquid chromatography of hexane extracts of this protein fraction resolved several peaks with polarity and relative retention times similar, but not identical to all-trans retinol and retinal and their 9-, 11-, and 13-cis isomers. Gas chromatography/mass spectrometry analysis of fatty acid methyl esters prepared following lipid extraction of the protein identified lauric, myristic, palmitic, palmitoleic, and oleic acids as being covalently bound. Laurate, myristate, palmitate, and stearate were noncovalently bound. The apparent molecular mass of the Drosophila protein as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of the retinoid- and fatty acid-binding peak obtained by hydrophobic interaction chromatography of the size-exclusion fraction was similar to 70 kDa. (C) 1994 Academic Press, Inc. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1994 VL 312 IS 1 BP 158 EP 166 DI 10.1006/abbi.1994.1294 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX107 UT WOS:A1994NX10700022 PM 8031123 ER PT J AU PRUSSICK, R PLOTT, RT STANLEY, JR AF PRUSSICK, R PLOTT, RT STANLEY, JR TI RECURRENCE OF PEMPHIGUS-VULGARIS ASSOCIATED WITH INTERLEUKIN-2 THERAPY SO ARCHIVES OF DERMATOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; HUMAN B-CELLS; ADVANCED CANCER; IMMUNOTHERAPY; EXPERIENCE; CARCINOMA; GOLD AB Background: Immunotherapy with recombinant interleukin 2 may result in regression of metastatic cancer, particularly malignant melanoma and renal cell carcinoma. Observations: We describe a patient who received interleukin 2 immunotherapy for metastatic renal cell carcinoma. After his second course of treatment, he developed a recurrence of pemphigus vulgaris that had been in remission for 10 years. Conclusions: Interleukin 2 therapy may be associated with recurrence of an autoimmune disease, perhaps because of its ability to stimulate autoantibody production. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 19 TC 19 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 1994 VL 130 IS 7 BP 890 EP 893 PG 4 WC Dermatology SC Dermatology GA NX804 UT WOS:A1994NX80400010 PM 7794299 ER PT J AU ABANGAN, DL SOLOMON, D KAUFFMAN, CL AF ABANGAN, DL SOLOMON, D KAUFFMAN, CL TI SUSPICIOUS VIOLACEOUS SUBUNGUAL NODULE - METASTATIC RENAL-CELL CARCINOMA (RCC) SO ARCHIVES OF DERMATOLOGY LA English DT Note ID SKIN RP ABANGAN, DL (reprint author), NCI,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 1994 VL 130 IS 7 BP 915 EP & DI 10.1001/archderm.130.7.915 PG 0 WC Dermatology SC Dermatology GA NX804 UT WOS:A1994NX80400017 PM 8024282 ER PT J AU TORREY, EF AF TORREY, EF TI THE PREVALENCE OF SCHIZOPHRENIA IN IRELAND SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter RP TORREY, EF (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROPSYCHIAT,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1994 VL 51 IS 7 BP 513 EP 513 PG 1 WC Psychiatry SC Psychiatry GA NW199 UT WOS:A1994NW19900001 PM 8031222 ER PT J AU HOEG, JM FEUERSTEIN, IM TUCKER, EE AF HOEG, JM FEUERSTEIN, IM TUCKER, EE TI DETECTION AND QUANTITATION OF CALCIFIC ATHEROSCLEROSIS BY ULTRAFAST COMPUTED-TOMOGRAPHY IN CHILDREN AND YOUNG-ADULTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE LIPOPROTEINS; FAMILIAL HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; COMPUTED TOMOGRAPHY; DIAGNOSTIC IMAGING ID CORONARY-ARTERY DISEASE; LIVER-TRANSPLANTATION; HEART-DISEASE; GENE-THERAPY; LIPOPROTEIN; FLUOROSCOPY; DIAGNOSIS; ANGIOGRAPHY; GUIDELINES; STENOSIS AB Ultrafast computed tomography (CT) is a new method for detecting calcific lesions in the coronary arteries. The ability of CT to detect and quantify coronary artery atherosclerosis in children and young adults at risk for malignant atherogenesis was evaluated. A total of 11 consecutive familial hypercholesterolemic (FH) homozygotes (3 to 37 years old) participated. Untreated total cholesterol concentrations were 488 to 1277 mg/dL (12.7 to 33.2 mmol/L). Angiography detected significant lesions in 7 of 11 patients. CT detected calcific atherosclerosis in all 9 of the patients older than 12 years of age, including all those with angina. CT was more sensitive in detecting aortic root and coronary ostial lesions, where atherosclerosis first appears in homozygous FH. The volume of calcification (in cubic millimeters) correlated with the severity and duration of the hypercholesterolemia (r=.62, P<.05) as well as with the presence of angina (P<.05). All patients with angina (7 of 7) had >150 mm(3) of calcified volume, whereas only 1 of 4 asymptomatic patients had a volume score >150 mm(3). We conclude that (1) coronary and aortic calcium phosphate deposits are common in young FH homozygotes; (2) these deposits are associated with the presence of angiographic stenoses, as has been seen in adults with coronary atherosclerosis; and (3) aortic calcific deposits are more common than calcific coronary lesions. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD. HENRY M JACKSON FDN ADV MIL MED,BETHESDA,MD. RP HOEG, JM (reprint author), NHLBI,CELL BIOL SECT,MOLEC DIS BRANCH,BLDG 10,ROOM 7N115,BETHESDA,MD 20892, USA. NR 51 TC 97 Z9 97 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL PY 1994 VL 14 IS 7 BP 1066 EP 1074 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW013 UT WOS:A1994NW01300006 PM 8018661 ER PT J AU SHARRETT, AR PATSCH, W SORLIE, PD HEISS, G BOND, MG DAVIS, CE AF SHARRETT, AR PATSCH, W SORLIE, PD HEISS, G BOND, MG DAVIS, CE TI ASSOCIATIONS OF LIPOPROTEIN CHOLESTEROLS, APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-B, AND TRIGLYCERIDES WITH CAROTID ATHEROSCLEROSIS AND CORONARY HEART-DISEASE - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE ATHEROSCLEROSIS; CAROTID ARTERY DISEASES; CORONARY ARTERY DISEASE; LIPOPROTEINS; APOLIPOPROTEINS ID HIGH-DENSITY-LIPOPROTEIN; YOUNG MALE SURVIVORS; ARTERY DISEASE; MYOCARDIAL-INFARCTION; BLOOD COLLECTION; HDL-CHOLESTEROL; PARTICLE-SIZE; SERUM-LIPIDS; FACTOR-VII; PLASMA AB Previous research shows generally greater proportional elevation in apolipoprotein B (apoB) levels than in low-density lipoprotein cholesterol (LDL-C) in coronary heart disease (CHD) case subjects compared with control subjects. The Atherosclerosis Risk in Communities study provided general populations of 7261 men and women free of cardiovascular symptoms for evaluating the associations between intima-media thickening in extracranial carotid arteries measured using ultrasound imaging and fasting plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), apoB, apolipoprotein A-I (apoA-I), triglycerides, and HDL density subfractions. A CHD group was selected for comparison. Lipid factors show approximately linear associations with carotid thickness: positive for LDL-C and plasma apoB and negative for HDL-C and apoA-I levels. Apolipoproteins and HDL density subfractions did not contribute to the association after accounting for LDL-C and HDL-C. Compared with control subjects, persons whose carotid thickness exceeded 0.9 mm had greater proportional elevations in LDL-C than in apoB, whereas HDL-C reductions were small. CHD case subjects showed greater proportional elevations of apoB than LDL-C. Although the lipid profiles associated with asymptomatic carotid wall thickening and stenotic coronary disease are similar, the differences found suggest that LDL-C is the most important lipid factor in earlier stages of atherogenesis, whereas the metabolism of triglyceride-rich lipoproteins and its effects on LDL and HDL may be more relevant to later atherothrombotic processes. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT ANAT,WINSTON SALEM,NC 27103. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. RP SHARRETT, AR (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,FED BLDG,ROOM 2C08,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC55015, N01-HC55016, N01-HC55018] NR 52 TC 130 Z9 130 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL PY 1994 VL 14 IS 7 BP 1098 EP 1104 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW013 UT WOS:A1994NW01300011 PM 8018665 ER PT J AU MCINNES, PM SCHUTTINGA, J SANSLONE, WR STARK, SP KLIPPEL, JH AF MCINNES, PM SCHUTTINGA, J SANSLONE, WR STARK, SP KLIPPEL, JH TI THE ECONOMIC-IMPACT OF TREATMENT OF SEVERE LUPUS NEPHRITIS WITH PREDNISONE AND INTRAVENOUS CYCLOPHOSPHAMIDE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CONTROLLED TRIAL; ERYTHEMATOSUS; PREVALENCE; PROGNOSIS; DISEASES AB Objective. It has been reported that outcomes are improved in patients with severe lupus nephritis treated with combined prednisone and intravenous cyclophosphamide, compared with those treated with prednisone alone. These findings motivated this analysis of the economic impact of the combined therapy. Methods. The annual expected incidence of severe lupus nephritis in the year 1988 in the US was estimated to be 1,130. A hypothetical patient cohort of this size was used as the model for the present analysis; the costs of treatment with prednisone alone and with combined prednisone and intravenous cyclophosphamide were calculated and compared. The analysis took into account the expected rate of renal failure with each therapeutic approach, as well as age, sex, and the economic value of working years gained. Results. Although the treatment costs are higher for the combination therapy, the analysis revealed overall savings due to a reduced need for kidney dialysis or transplantation, acid the economic value of working capacity gained. Savings attributable to patient care costs were $50.8 million; those attributable to working capacity gained were $42.3 million. Conclusion. This analysis indicates that over a l0-year period, as much as $93.1 million per annual cohort is saved by the use of combination therapy for the treatment of severe lupus nephritis. C1 NIAMSD,PLANNING & EVALUATION PROGRAM OFF,BETHESDA,MD 20892. NIH,SCI POLICY & TECHNOL TRANSFER OFF,BETHESDA,MD 20892. NR 23 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1994 VL 37 IS 7 BP 1000 EP 1006 DI 10.1002/art.1780370704 PG 7 WC Rheumatology SC Rheumatology GA NW274 UT WOS:A1994NW27400004 PM 8024609 ER PT J AU POHL, LR MARTIN, JL HARGUS, SJ AF POHL, LR MARTIN, JL HARGUS, SJ TI IMMUNOCHEMICAL METHODS OF STUDYING THE MECHANISM OF DICLOFENAC-INDUCED ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Note ID NONCOVALENT INTERACTIONS; HEPATITIS; HEPATOTOXICITY; COVALENT RP POHL, LR (reprint author), NHLBI,BETHESDA,MD, USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1994 VL 37 IS 7 BP 1112 EP 1112 DI 10.1002/art.1780370719 PG 1 WC Rheumatology SC Rheumatology GA NW274 UT WOS:A1994NW27400019 PM 8024621 ER PT J AU TRABER, MG RADER, D ACUFF, RV BREWER, HB KAYDEN, HJ AF TRABER, MG RADER, D ACUFF, RV BREWER, HB KAYDEN, HJ TI DISCRIMINATION BETWEEN RRR-RACEMIC-ALPHA-TOCOPHEROL AND ALL-RACEMIC-ALPHA-TOCOPHEROL LABELED WITH DEUTERIUM BY PATIENTS WITH ABETALIPOPROTEINEMIA SO ATHEROSCLEROSIS LA English DT Article DE VITAMIN-E; TOCOPHEROL BINDING PROTEIN; LIPOPROTEINS; STEREOISOMERS ID VITAMIN-E-DEFICIENCY; HUMAN LIPOPROTEINS; TRANSFER PROTEIN; BINDING-PROTEIN; RAT-LIVER; GAMMA-TOCOPHEROL; STEREOISOMERS; PURIFICATION; PLASMA; IDENTIFICATION AB The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol. An oral dose containing 3.7 g of each 2R,4'R,8'R-alpha-[5-(CH3)-H-2,]tocopheryl acetate (d(3)RRR-alpha-tocopheryl acetate) and 2RS,4'RS,8'RS-alpha-[5,7-((CH3)-H-2)(2)]tocopheryl acetate (d(6)all rac-alpha-tocopheryl acetate) was administered, then the labeled and unlabeled alpha-tocopherol contents of plasma and red blood cells from multiple blood samples obtained at selected times up to 72 h following the dose were quantitated. ABL plasma contained about 1%-10% of the d(3)-RRR-alpha-tocopherol concentrations of normal subjects given only 150 mg of each isotope. Three of the patients discriminated between forms of alpha-tocopherol with ratios of RRR-/allrac-alpha-tocopherol greater than or equal to 1.8, similar to normals. These data suggest that the hepatic tocopherol binding protein is present and functional in ABL patients. Although two of the patients did not discriminate between stereoisomers of alpha-tocopherol, it is likely that this resulted from nearly a complete block in very low density lipoprotein (VLDL) secretion. Thus, the ability of ABL patients to absorb and transport orally administered vitamin E is markedly impaired and variable among patients. C1 NYU, SCH MED, DEPT MED, NEW YORK, NY 10016 USA. NHLBI, BETHESDA, MD 20892 USA. E TENNESSEE STATE UNIV, JAMES H QUILLEN COLL MED, DEPT SURG, JOHNSON CITY, TN 37614 USA. OI Traber, Maret/0000-0002-2892-4024 FU NHLBI NIH HHS [HL 30842] NR 40 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL PY 1994 VL 108 IS 1 BP 27 EP 37 DI 10.1016/0021-9150(94)90035-3 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA483 UT WOS:A1994PA48300004 PM 7980705 ER PT J AU WARD, GE CHITNIS, CE MILLER, LH AF WARD, GE CHITNIS, CE MILLER, LH TI THE INVASION OF ERYTHROCYTES BY MALARIAL MEROZOITES SO BAILLIERES CLINICAL INFECTIOUS DISEASES LA English DT Review ID PLASMODIUM-FALCIPARUM MEROZOITES; RED-CELL INVASION; PARASITOPHOROUS VACUOLE MEMBRANE; TOXOPLASMA-GONDII; HOST-CELL; SURFACE-ANTIGEN; DENSE GRANULES; MONOCLONAL-ANTIBODIES; KNOWLESI MEROZOITES; PROTEASE INHIBITORS RP WARD, GE (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 179 TC 20 Z9 20 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1071-6564 J9 BAILLIERE CLIN INF D JI Baillieres Clin. Infect. Dis. PD JUL PY 1994 VL 1 IS 2 BP 155 EP 190 PG 36 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QA994 UT WOS:A1994QA99400002 ER PT J AU MILLER, VL PEPE, JC AF MILLER, VL PEPE, JC TI THE INVASION GENES OF YERSINIA - INV, AIL AND YADA SO BAILLIERES CLINICAL INFECTIOUS DISEASES LA English DT Article ID OUTER-MEMBRANE PROTEIN; SALMONELLA-TYPHIMURIUM VIRULENCE; MEDIATES SPECIFIC BINDING; CULTURED MAMMALIAN-CELLS; ESCHERICHIA-COLI K-12; PSEUDOTUBERCULOSIS INVASIN; HELA-CELLS; ENTEROPATHOGENIC YERSINIAE; ENTEROCOLITICA STRAINS; Y-PSEUDOTUBERCULOSIS C1 UNIV WASHINGTON,SCH MED,DEPT MICROBIOL,SEATTLE,WA 98195. RP MILLER, VL (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 92 TC 1 Z9 1 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1071-6564 J9 BAILLIERE CLIN INF D JI Baillieres Clin. Infect. Dis. PD JUL PY 1994 VL 1 IS 2 BP 213 EP 226 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QA994 UT WOS:A1994QA99400004 ER PT J AU SUGIMOTO, Y AKSENTIJEVICH, I GOTTESMAN, MM PASTAN, I AF SUGIMOTO, Y AKSENTIJEVICH, I GOTTESMAN, MM PASTAN, I TI EFFICIENT EXPRESSION OF DRUG-SELECTABLE GENES IN RETROVIRAL VECTORS UNDER CONTROL OF AN INTERNAL RIBOSOME ENTRY SITE SO BIO-TECHNOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN GENE; BONE-MARROW; TRANSGENIC MICE; MAMMALIAN-CELLS; BRAIN-TUMORS; MDR1 CDNA; DNA; THERAPY; INVIVO AB We describe a new retroviral vector system pSXLC/pHa that utilizes a putative internal ribosome entry site (IRES) from encephalomyocarditis virus downstream from a multicloning site to co-express drug-selectable markers with a second non-selectable cDNA in a eukaryotic expression vector. The positive drug-selectable marker, MDR1, and the positive-negative marker, herpes simplex virus thymidine kinase (HSV-TK), were successfully introduced and expressed in the pSXLC/pHa system. The pSXLC-MDR and pSXLC-TK vectors contain the drug-selectable genes under translational control of the IRES and multiple cloning sites upstream for insertion of second cDNAs which can be co-expressed in this system. The inserts of these pSXLC plasmids were designed for easy transfer to the pHa retrovirus vector which has a strong promoter from Harvey murine sarcoma virus. The IRES-MDR-carrying retroviral vector, pHaMCS-IRES-MDR, conferred resistance to vincristine and adriamycin. The IRES-TK-containing vector, pHa-MCS-IRES-TK conferred HAT-resistance in TK-deficient cells and the transfectants showed hypersensitivity to ganciclovir. These ''flexible'' vectors should be useful for co-expression of genes for selectable gene transfer and for positive-negative (suicide) selections in vitro and in vivo. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 28 TC 72 Z9 74 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD JUL PY 1994 VL 12 IS 7 BP 694 EP 698 DI 10.1038/nbt0794-694 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA NU370 UT WOS:A1994NU37000023 PM 7764914 ER PT J AU ELKEBBI, IM ROSER, S POLLET, RJ CUSHMAN, SW WILSON, CM AF ELKEBBI, IM ROSER, S POLLET, RJ CUSHMAN, SW WILSON, CM TI REGULATION OF THE GLUT1 GLUCOSE-TRANSPORTER IN CULTURED MYOCYTES - TOTAL NUMBER AND SUBCELLULAR-DISTRIBUTION AS DETERMINED BY PHOTOAFFINITY-LABELING SO BIOCHEMICAL JOURNAL LA English DT Article ID RAT ADIPOSE-CELLS; INSULIN-INDUCED TRANSLOCATION; HUMAN SKELETAL-MUSCLE; PROTEIN-KINASE-C; 3T3-L1 ADIPOCYTES; RESPONSIVE TISSUES; HEXOSE TRANSPORTER; PHORBOL ESTER; SURFACE; STIMULATION AB We have used the impermeant photoaffinity label 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-[2-H-3]1,3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-[2-H-3]BMPA) to identify and quantify the glucose transporters on the surface of BC3H-1 cells, a continuously cultured skeletal-muscle cell line lacking the MyoD transcription factor required for cell fusion. ATB-[2-H-3]BMPA was used in combination with immunoprecipitation of the GLUT1 glucose transporter, the only isoform expressed in these cells. The total cellular GLUT1 content was also determined by photolabelling and immunoprecipitation after cell permeabilization with digitonin (0.025 %). In glucose-starved cells, 85 % of the glucose transporters were present at the cell surface in the basal state, with little change in response to insulin (200 nM), correlating with lack of additional 2-deoxyglucose uptake in response to insulin. Feeding the cells with glucose (25 mM) for 24 h resulted in an 80 % decrease in the total GLUT1 content relative to starved cells, of which only 25 % were present on the cell surface. This was associated with an 85 % decrease in 2-deoxyglucose uptake. In addition, acute stimulation of the fed cells with insulin or phorbol 12-myristate 13-acetate (PMA) led to an increase in GLUT1 at the cell surface, and, in correspondence, an increase in 2-deoxyglucose uptake by approx. 2- and 4-fold respectively. We conclude that exofacial photoaffinity labelling of glucose transporters with ATB-[2-H-3]BMPA in the presence and absence of digitonin, followed by specific immunoprecipitation, provides an accurate measure of total and cell-surface glucose transporters in differentiated BC3H-1 muscle cells. This technique demonstrates that glucose pre-feeding (1) decreases the total number of GLUT1 and (2) redistributes the majority of the remaining transporters to an intracellular site, where they can now be translocated to the cell surface in response to insulin and PMA. C1 VET ADM MED CTR,DEPT MED,ATLANTA,GA 30033. EMORY UNIV,SCH MED,DECATUR,GA 30033. NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 38 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 1994 VL 301 BP 35 EP 40 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY661 UT WOS:A1994NY66100008 PM 8037688 ER PT J AU KUZNICKI, J WINSKY, L JACOBOWITZ, DM AF KUZNICKI, J WINSKY, L JACOBOWITZ, DM TI CA2+-DEPENDENT AND INDEPENDENT INTERACTIONS OF CALRETININ WITH HYDROPHOBIC RESINS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID CALCIUM-BINDING PROTEINS; TROPONIN-C; CONFORMATIONAL TRANSITION; DEPENDENT INTERACTION; SEQUENCE-ANALYSIS; CALMODULIN; BRAIN; CALBINDIN-D28K; RECOGNITION; INHIBITION RP KUZNICKI, J (reprint author), NIMH,CLIN SCI LAB,BETHESDA,MD 20892, USA. NR 37 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUL PY 1994 VL 33 IS 4 BP 713 EP 721 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA059 UT WOS:A1994PA05900012 PM 7981659 ER PT J AU BENHAR, I BRINKMANN, U WEBBER, KO PASTAN, I AF BENHAR, I BRINKMANN, U WEBBER, KO PASTAN, I TI MUTATIONS OF 2 LYSINE RESIDUES IN THE CDR LOOPS OF A RECOMBINANT IMMUNOTOXIN THAT REDUCE ITS SENSITIVITY TO CHEMICAL DERIVATIZATION SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; PROTEINS; BINDING AB B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of monoclonal antibody B3 is connected to a truncated form of Pseudomonas exotoxin. It would be desirable to use the lysine residues of the molecule for chemical modification so that it can be derivatized with poly(ethylene glycol) to achieve reduced immunogenicity or with the Bolton-Hunter reagent for biodistribution studies. We found that derivatizing lysine residues of B3(Fv)-PE38 causes a marked loss of specific target cell cytotoxicity and/or immunoreactivity. Here we show that two lysine residues in the antibody-combining region of B3(Fv)-PE38 can be replaced with arginines, with only a small loss of cytotoxicity and no change in specificity. This mutant molecule is 3-fold more resistant to inactivation by derivatization with succinimidyl 4-(N-maleimidomethyl)cyclohexanel-carboxylate (SMCC) or Bolton-Hunter reagent. C1 NCI,DIV CANC BIOL DIAGN & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 22 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1994 VL 5 IS 4 BP 321 EP 326 DI 10.1021/bc00028a007 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NZ269 UT WOS:A1994NZ26900007 PM 7948099 ER PT J AU COPLEN, TB HARPER, IT AF COPLEN, TB HARPER, IT TI AN IMPROVED TECHNIQUE FOR THE H-2 H-1 ANALYSIS OF URINES FROM DIABETIC VOLUNTEERS SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID WATER; HYDROGEN AB The H-2-H2O ambient-temperature equilibration technique for the determination of H-2/H-1 ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, similar to 1-2 parts per thousand, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. RP COPLEN, TB (reprint author), US GEOL SURVEY,431 NATL CTR,RESTON,VA 22092, USA. NR 5 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD JUL PY 1994 VL 23 IS 7 BP 437 EP 439 DI 10.1002/bms.1200230709 PG 3 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA NW622 UT WOS:A1994NW62200008 PM 8068739 ER PT J AU SHETTY, HU HOLLOWAY, HW AF SHETTY, HU HOLLOWAY, HW TI ASSAY OF MYOINOSITOL IN CEREBROSPINAL-FLUID AND PLASMA BY CHEMICAL-IONIZATION MASS-SPECTROMETRY OF THE HEXAACETATE DERIVATIVE SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID DOWNS-SYNDROME; ALZHEIMER-DISEASE; MYOINOSITOL; BRAIN; POLYOLS AB The paper describes a capillary gas chromatographic/mass spectrometric technique to quantitate myo-inositol in cerebrospinal fluid (CSF) and plasma. A highly abundant fragment ion, m/z 373, for the hexaacetate derivative of myo-inositol was generated by chemical ionization (CI). This ion and the analogous ion of hexadeuterated myo-inositol (the internal standard), m/z 379, were both monitored in the assay. CI was performed with acetonitrile vapor in an ion trap mass spectrometer. Microliter quantities of CSF or plasma were mixed with the internal standard, dried and acetylated. After a post-derivatization clean-up, samples were analyzed on a capillary gas chromatograph interfaced with a Finnigan ion trap. Standard curves constructed for both CSF and plasma were linear and reproducible. Absence of matrix effects and good precision in the results indicate the suitability of the technique for critical assays. Results from the determination of myo-inositol in the CSF and plasma of healthy subjects and those with neurological deficits are reported. RP SHETTY, HU (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 103,BETHESDA,MD 20892, USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD JUL PY 1994 VL 23 IS 7 BP 440 EP 444 DI 10.1002/bms.1200230710 PG 5 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA NW622 UT WOS:A1994NW62200009 PM 8068740 ER PT J AU BYSTRICKY, S SZU, SC AF BYSTRICKY, S SZU, SC TI O-ACETYLATION AFFECTS THE BINDING-PROPERTIES OF THE CARBOXYL GROUPS ON THE VI BACTERIAL POLYSACCHARIDE SO BIOPHYSICAL CHEMISTRY LA English DT Article DE N-ACETYLGALACTOSAMINURONIC ACID; O-ACETYLATION; POTENTIOMETRIC TITRATION; BINDING FREE ENERGY; CIRCULAR DICHROISM ID CAPSULAR POLYSACCHARIDE; TYPHOID-FEVER; CALCIUM-IONS; CONFORMATION; SUBSTANCES; PECTIN AB The capsular polysaccharide of Salmonella typhi and Citrobacter freundii (Vi) is a linear homopolymer of (1 --> 4)-linked 2-acetamido-2-deoxy-alpha-D-galactopyranosyluronic acid partially O-acetylated at the C-3 position. The physico-chemical properties of the carboxyl groups of the Vi polysaccharide, as a function of different degrees of O-acetylation, were studied by potentiometric titration, circular dichroism, and their reaction with the bulky nucleophile 2-nitro-phenylhydrazine (NPH). Potentiometric titrations with K+ and Ca2+ hydroxides showed that the difference in the free energy of binding between the two cations (Delta G(K)(Ca)) was inversely proportional to the degree of O-acetylation. Similar cationic effects were found when measuring circular dichroism. Moreover there was also an inverse relation between the degree of O-acetylation and the extent of binding of NPH to the carboxyl groups. These data all indicate that O-acetyl groups hinder the association of carboxyls with cations and nucleophilic reagents. This provides a possible explanation for the importance of the O-acetyl and the relative unimportance of the carboxyl groups in contributing to the immunologic properties of the Vi. C1 SLOVAK ACAD SCI,INST CHEM,BRATISLAVA,SLOVAKIA. RP BYSTRICKY, S (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 33 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JUL PY 1994 VL 51 IS 1 BP 1 EP 7 DI 10.1016/0301-4622(94)00002-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA NV848 UT WOS:A1994NV84800001 PM 8061223 ER PT J AU LYON, RC MCLAUGHLIN, AC AF LYON, RC MCLAUGHLIN, AC TI DOUBLE-QUANTUM-FILTERED NA-23 NMR-STUDY OF INTRACELLULAR SODIUM IN THE PERFUSED LIVER SO BIOPHYSICAL JOURNAL LA English DT Article ID SHIFT-REAGENTS; RAT-HEART; RELAXATION; TISSUE; CELLS; SPINS; IONS AB We acquired double-quantum-filtered Na-23 NMR spectra from perfused liver, using a range of tau values from 0.2 to 24 ms, where tau is the separation between the first and second pi/2 pulses in the radio-frequency pulse sequence. For each tau value we compared the amplitude of the double-quantum-filtered Na-23 NMR signal acquired from intracellular sodium ions when the liver was perfused with buffer containing the ''shift reagent'' Dy(PPP)(2) to the amplitude of the total double-quantum-filtered Na-23 NMR signal acquired when the liver was perfused with buffer containing no Dy(PPP)(2). For tau less than or equal to( )4 ms, the average ratio of the two amplitudes was 0.98 +/- 0.03 (mean +/- SEM). For tau less than or equal to 8 ms, the average ratio was significantly less than 1. These results demonstrate that double-quantum-filtered Na-23 NMR signals acquired from perfused liver using short tau values arise almost exclusively from intracellular sodium ions, but double-quantum-filtered Na-23 NMR signals acquired from perfused liver using long tau values contain contributions from both intracellular and extracellular sodium ions. This conclusion suggests that multiple-quantum-filtered Na-23 NMR spectroscopy will be useful in studying intracellular sodium levels in the perfused liver, and possibly in the intact liver in vivo. C1 NIAAA,BETHESDA,MD 20892. NR 23 TC 13 Z9 13 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1994 VL 67 IS 1 BP 369 EP 376 PG 8 WC Biophysics SC Biophysics GA NT472 UT WOS:A1994NT47200045 PM 7919009 ER PT J AU NOREL, R LIN, SL WOLFSON, HJ NUSSINOV, R AF NOREL, R LIN, SL WOLFSON, HJ NUSSINOV, R TI SHAPE COMPLEMENTARITY AT PROTEIN-PROTEIN INTERFACES SO BIOPOLYMERS LA English DT Article ID MOLECULAR RECOGNITION; AUTOMATED DOCKING; ALGORITHM AB A matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by ''critical points,'' describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229-1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the other hand, matchings of fewer critical points require a very time-consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746-750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein-protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter. As a geometrically based docking methodology predicts correct, along with incorrect, receptor-ligand bound conformations, all solutions need to undergo energy screening to differentiate between them. (C) 1994 John Wiley & Sons, Inc. C1 TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,MATH BIOL LAB,FREDERICK,MD 21712. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011; OI Norel, Raquel/0000-0001-7737-4172 FU NCI NIH HHS [1-CO-74102] NR 18 TC 85 Z9 86 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JUL PY 1994 VL 34 IS 7 BP 933 EP 940 DI 10.1002/bip.360340711 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NR431 UT WOS:A1994NR43100010 PM 8054472 ER PT J AU DACUNHA, A AF DACUNHA, A TI A DEVICE THAT FACILITATES CUTTING FROZEN BIOLOGICAL SPECIMENS SO BIOTECHNIQUES LA English DT Note RP DACUNHA, A (reprint author), NIMH,MOLEC NEUROSCI SECT,CELL BIOL LAB,BLDG 36,ROOM 3A17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1994 VL 17 IS 1 BP 68 EP 69 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW384 UT WOS:A1994NW38400017 PM 7946318 ER PT J AU WANG, RY DIENEL, GA AF WANG, RY DIENEL, GA TI ION CHROMATOGRAPHY WITH SUPPRESSED CONDUCTIVITY DETECTION - RECOVERIES OF C-14 LABELED METABOLITES SO BIOTECHNIQUES LA English DT Note ID RAT-BRAIN AB Suppressed conductivity detection, developed for use with ion chromatography, might be useful to assay specific activities of organic acids after metabolic labeling. Because the suppressor reduces background conductivity by acid-base neutralization and removal of ions from the eluent, it could influence recoveries and apparent retention times of labeled compounds. Elution times of C-14-labeled glucose and neutral amino acids, compounds not detected by conductivity, from the analytical column were found to be similar to those of lactate and acetate. When the suppressor was connected to the HPLC system in the recycle mode, the apparent ebltion times of amino acids increased and various organic acid fractions would be contaminated. When the suppressor was used in the external water mode, the labeled neutral amino acids and portions of acidic amino acids were recovered in the waste fraction; this indicated that recoveries of total C-14 in the analyte fraction would be incomplete if the loss were not taken into account. Thus, the procedure to insert the suppressor into the system influences the apparent retention times and the recoveries of labeled amino acids in the analyte fraction; labeled metabolites not detected by conductivity can cause serious errors in specific activities of organic acids and should be removed from the sample prior to analysis. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 3 TC 2 Z9 2 U1 1 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1994 VL 17 IS 1 BP 106 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW384 UT WOS:A1994NW38400025 PM 7946292 ER PT J AU LI, F LINTON, GF SEKHSARIA, S WHITINGTHEOBALD, N KATKIN, JP GALLIN, JI MALECH, HL AF LI, F LINTON, GF SEKHSARIA, S WHITINGTHEOBALD, N KATKIN, JP GALLIN, JI MALECH, HL TI CD34+ PERIPHERAL-BLOOD PROGENITORS AS A TARGET FOR GENETIC CORRECTION OF THE 2 FLAVOCYTOCHROME-B(558) DEFECTIVE FORMS OF CHRONIC GRANULOMATOUS-DISEASE SO BLOOD LA English DT Note ID NEUTROPHIL CYTOCHROME-B; RESPIRATORY BURST OXIDASE; NADPH OXIDASE; SUPEROXIDE GENERATION; CHROMOSOMAL LOCATION; LIGHT CHAIN; CELL-LINE; EXPRESSION; CLONING; CDNA C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 38 TC 68 Z9 70 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 JUL 1 PY 1994 VL 84 IS 1 BP 53 EP 58 PG 6 WC Hematology SC Hematology GA NV959 UT WOS:A1994NV95900008 PM 7517218 ER PT J AU LINNEKIN, D HOWARD, OMZ PARK, L FARRAR, W FERRIS, D LONGO, DL AF LINNEKIN, D HOWARD, OMZ PARK, L FARRAR, W FERRIS, D LONGO, DL TI HCK EXPRESSION CORRELATES WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-INDUCED PROLIFERATION IN HL-60 CELLS SO BLOOD LA English DT Article ID PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; LEUKEMIA-CELLS; INTERLEUKIN-3 RECEPTORS; ERYTHROPOIETIN RECEPTOR; CSF RECEPTOR; MICE LACKING; ZETA-CHAIN; GENE HCK C1 PROGRAM RESOURCES INC DYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. IMMUNEX RES & DEV CORP,DEPT BIOCHEM,SEATTLE,WA 98101. RP LINNEKIN, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 70 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1994 VL 84 IS 1 BP 94 EP 103 PG 10 WC Hematology SC Hematology GA NV959 UT WOS:A1994NV95900013 PM 8018933 ER PT J AU HESTDAL, K RUSCETTI, FW CHIZZONITE, R ORTIZ, M GOOYA, JM LONGO, DL KELLER, JR AF HESTDAL, K RUSCETTI, FW CHIZZONITE, R ORTIZ, M GOOYA, JM LONGO, DL KELLER, JR TI INTERLEUKIN-1 (IL-1) DIRECTLY AND INDIRECTLY PROMOTES HEMATOPOIETIC-CELL GROWTH THROUGH TYPE-I IL-1 RECEPTOR SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW CELLS; GRANULOCYTE-MACROPHAGE; INTERLEUKIN-1 RECEPTORS; PROGENITOR CELLS; STEM-CELLS; INVIVO; HEMOPOIETIN-1; MICE; FIBROBLASTS C1 NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. HOFFMANN LA ROCHE INC, DEPT IMMUNOPHARMACOL & MOLEC GENET, NUTLEY, NJ 07110 USA. NR 40 TC 28 Z9 28 U1 1 U2 1 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 JUL 1 PY 1994 VL 84 IS 1 BP 125 EP 132 PG 8 WC Hematology SC Hematology GA NV959 UT WOS:A1994NV95900017 PM 8018912 ER PT J AU RAY, ME GUAN, XY SLOVAK, ML TRENT, JM MELTZER, PS AF RAY, ME GUAN, XY SLOVAK, ML TRENT, JM MELTZER, PS TI RAPID DETECTION, CLONING AND MOLECULAR CYTOGENETIC CHARACTERIZATION OF SEQUENCES FROM AN MRP-ENCODING AMPLICON BY CHROMOSOME MICRODISSECTION SO BRITISH JOURNAL OF CANCER LA English DT Article ID CANCER CELL-LINE; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; DOXORUBICIN RESISTANCE; AMPLIFIED DNA; GENE; AMPLIFICATION; ADRIAMYCIN; MECHANISMS AB Chromosome microdissection was utilised For the analysis of cytogenetic markers of gene amplification [homogeneously staining regions (hsrs) and double minutes (dmins)] in two doxorubicin-resistant cell lines, fibrosarcoma HT1080/DR4 and small-cell lung cancer H69AR. Microdissection products from the hsr(7)(p12p15) of HT1080/DR4 were amplified and used for fluorescent in situ hybridisation (micro-FISH) analysis of drug-sensitive HT1080, resistant HT1080/DR4 and normal lymphocytes. The results demonstrated that the hsr contains a domain of DNA amplification of complex origin including sequences derived from 16p11.2-16p13.1, 2911.2, 7q32-7934 and 10q22. The amplification was confirmed by converting the microdissected probe into a microclone library for probing HT1080 and HT1080/DR4 Southerns. A micro-FISH probe from normal band region 16p11-16p13 further demonstrated amplification of 16p sequences in both HT1080/DR4 and H69AR. During the course of this analysis, Cole er al. (1992) (Science, 258, 1650-1653) published the amplification of the MRP gene in H69AR cells, which maps to chromosome 16p13.1. Our results corroborate the finding of MRP amplification in these doxorubicin-resistant cell lines, but, importantly, they provide information on the composition of the complex amplicon contributions from four different chromosomes. This study demonstrates the potential utility of chromosome microdissection for the rapid recovery of sequences from amplified regions in drug-resistant cells. C1 UNIV MICHIGAN, SCH MED, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. NIH, NATL CTR RES RESOURCES, CANC GENET LAB, BETHESDA, MD 20892 USA. CITY HOPE NATL MED CTR, DEPT CYTOGENET, DUARTE, CA 91010 USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCPDCID CDC HHS [CIA-33572] NR 24 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1994 VL 70 IS 1 BP 85 EP 90 DI 10.1038/bjc.1994.254 PG 6 WC Oncology SC Oncology GA NW118 UT WOS:A1994NW11800015 PM 8018546 ER PT J AU MINCGOLOMB, D TSARFATY, I SCHWARTZ, JP AF MINCGOLOMB, D TSARFATY, I SCHWARTZ, JP TI EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE BY NEURONS FOLLOWING EXPOSURE TO ENDOTOXIN AND CYTOKINE SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE CEREBELLAR GRANULE CELLS; MACROPHAGE; CEREBELLUM; INTERFERON-GAMMA; LIPOPOLYSACCHARIDE ID GLUTAMATE; RECEPTOR AB In the CNS, nitric oxide (NO) has been implicated as both a mediator of neurotoxicity and a neuromodulator. The inducible NO synthase (iNOS), thought to mediate toxic effects of NO, has been attributed to glial cells in the CNS. We now report that cerebellar granule cell neurones can be stimulated by lipopolysaccharide and interferon-gamma to express iNOS in vitro, as demonstrated by reverse transcription-polymerase chain reaction and fluorescent in situ hybridisation. The expression of both constitutive NO synthase (cNOS) and iNOS by neurones suggests that NO has diverse functions in the brain, and supports the possibility that iNOS plays a role in neuronal damage and inflammation following activation of brain microglia and production of cytokines. C1 NCI,ABL,BETHESDA,MD 20892. RP MINCGOLOMB, D (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892, USA. NR 10 TC 136 Z9 136 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1994 VL 112 IS 3 BP 720 EP 722 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV137 UT WOS:A1994NV13700002 PM 7522856 ER PT J AU FAN, P AF FAN, P TI EFFECTS OF ANTIDEPRESSANTS ON THE INWARD CURRENT MEDIATED BY 5-HT3 RECEPTORS IN RAT NODOSE GANGLION NEURONS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT3 RECEPTOR; DESENSITIZATION; PATCH CLAMP; NODOSE GANGLION NEURON; IMIPRAMINE; FLUOXETINE; PHENELZINE ID HUMAN-BRAIN INVITRO; ANTAGONISTS; MOUSE; 5-HYDROXYTRYPTAMINE; FLUOXETINE; BLOCKADE; DRUGS; SITES; CELLS AB 1 Effects of three different categories of antidepressants, imipramine (tricyclic), fluoxetine (selective 5-hydroxytryptamine (5-HT) uptake inhibitor), phenelzine and iproniazid (monoamine oxidase (MAO) inhibitor) on the inward current mediated by 5-HT3 receptors were investigated in rat nodose ganglion neurones. The whole-cell patch-clamp technique was used for recording the 5-HT current. 2 All the antidepressants tested inhibited the peak 5-HT current. The inhibition gradually reached a steady level and the recovery was incomplete when antidepressants were removed. IC50 values for imipramine, fluoxetine and phenelzine were 0.54 mu M, 1.3 mu M and 4.2 mu M respectively. The correspondent Hill coefficients were 0.9, 0.87 and 0.92. 3 The antidepressants examined increased the rate of 5-HT current desensitization. IC50 values for imipramine, fluoxetine and phenelzine on the decrease in desensitization time constant were 0.11 mu M, 0.18 mu M and 2.4 mu M respectively. The correspondent Hill coefficients were 0.9, 1.14 and 1.06. 4 Intracellular applications of the protein kinase inhibitor, H-7 (100 mu M), GDP-beta-S (2 mM) and the calcium chelator BAPTA (20 mM) did not affect the 5-HT current and the actions of antidepressants on 5-HT current. 5 These results suggest that the 5-HT3 receptor is an acting site for the therapeutic use of antidepressants. The present observation is also helpful in explaining the analgesic effect of antidepressants seen in pain clinics. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 26 TC 50 Z9 51 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1994 VL 112 IS 3 BP 741 EP 744 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV137 UT WOS:A1994NV13700006 PM 7522857 ER PT J AU FAN, P AF FAN, P TI MEPACRINE-INDUCED INHIBITION OF THE INWARD CURRENT MEDIATED BY 5-HT3 RECEPTORS IN RAT NODOSE GANGLION NEURONS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE NODOSE GANGLION; MEPACRINE; QUINACRINE; 5-HT3 RECEPTOR; PATCH-CLAMP ID NEUROBLASTOMA-CELLS; ION CURRENT; PHOSPHOLIPASE-A2 ACTIVITY; ACETYLCHOLINE-RECEPTOR; ETHANOL POTENTIATION; ARACHIDONIC-ACID; ELECTRIC ORGAN; QUINACRINE; BLOCK; CONTRACTIONS AB 1 With the whole-cell patch clamp technique, the effect of the antimalarial drug, mepacrine (quinacrine) on the inward current mediated by 5-HT3 receptors (5-hydroxytryptamine (5-HT)-induced current) was investigated in isolated nodose ganglion neurones of the rat. 2 5-HT and the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide elicited an inward current which reversed at around 0 mV and quickly desensitized to a steady state level. 3 Mepacrine dose-dependently inhibited the peak current induced by 5-HT with an IC50 of 2.1 mu M and an apparent Hill coefficient of 0.99. 4 Mepacrine increased the decay rate of the 5-HT-induced current. 5 The effect of mepacrine on the 5-HT-induced current was reversible and not dependent on membrane potential. The reversal potential of the 5-HT-induced current was not affected. 6 Intracellular mepacrine had no significant effect on the 5-HT-induced current and did not block the extracellular action of mepacrine. 7 Concentration-response curves in the presence and absence of mepacrine suggest a non-competitive inhibition of 5-HT-induced current by mepacrine. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 26 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1994 VL 112 IS 3 BP 745 EP 748 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV137 UT WOS:A1994NV13700007 PM 7522858 ER PT J AU DURCAN, MJ MORGAN, PF VANETTEN, ML LINNOILA, M AF DURCAN, MJ MORGAN, PF VANETTEN, ML LINNOILA, M TI COVARIATION OF ALPHA(2)-ADRENOCEPTOR DENSITY AND FUNCTION FOLLOWING IRREVERSIBLE ANTAGONISM WITH EEDQ SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE (EEDQ); ALPHA(2)-ADRENOCEPTORS; RX 821002; MEDETOMIDINE; SEDATION; HYPOTHERMIA; RECEPTOR BINDING IN MICE ID N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE EEDQ; RAT-BRAIN; DOPAMINE-RECEPTORS; OCCUPANCY INVIVO; BINDING-SITES; H-3 IDAZOXAN; FAT-CELLS; ALPHA-2-ADRENOCEPTORS; INACTIVATION; TURNOVER AB 1 Administration of the irreversible antagonist, N-ethoxycarbonyl-2-ethoxy- 1,2-dihydroquinoline, (EEDQ, 2 mg kg(-1), i.p.) to mice reduced binding of [H-3]-RX 821002 (2-methoxy-idazoxan) to alpha(2)-adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2 EEDQ administration also resulted in the loss of the sedative effect of the alpha(2)-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post EEDQ administration. 3 EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg(-1) i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration. 4 Pretreatment with the selective alpha(2)-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg(-1), i.p.) 45 min before EEDQ prevented the loss of alpha(2)-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ. 5 The results of these experiments indicate that there is significant receptor reserve for alpha(2)-adrenoceptor-mediated behavioural and physiological responses. C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 25 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1994 VL 112 IS 3 BP 855 EP 860 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV137 UT WOS:A1994NV13700024 PM 7921612 ER PT J AU ELTOUM, IA TAHA, TE SAAD, AM SULIMAN, SM BENNETT, JL NASH, TE HOMEIDA, MM AF ELTOUM, IA TAHA, TE SAAD, AM SULIMAN, SM BENNETT, JL NASH, TE HOMEIDA, MM TI PREDICTORS OF UPPER GASTROINTESTINAL-BLEEDING IN PATIENTS WITH SCHISTOSOMAL PERIPORTAL FIBROSIS SO BRITISH JOURNAL OF SURGERY LA English DT Article ID ESOPHAGEAL-VARICES; MANSONI INFECTION; SUDAN; ULTRASOUND; DIAGNOSIS; GEZIRA AB A case-control study was conducted between 1985 and 1987 in the Gezira-Managil area of central Sudan to assess the major predictors of haematemesis. Eighty-four patients who had suffered at least one attack of oesophageal bleeding and had schistosomal periportal fibrosis demonstrated by ultrasonography were compared with 173 subjects with-out bleeding but with ultrasonographic evidence of periportal fibrosis. A splenic longitudinal dimension of more than 11 cm, periportal fibrosis worse than grade I and varices more than grade I were independently associated with a significant risk of variceal bleeding. Age, sex, presence of a palpable liver and portal vein diameter were not associated with a significant risk of bleeding after adjustment for potential confounding variables. Factors identified in this study could be helpful in the prophylactic management of patients with complicated schistosomiasis. C1 UNIV KHARTOUM,FAC MED,DEPT SURG,KHARTOUM,SUDAN. UNIV KHARTOUM,FAC MED,DEPT PATHOL,KHARTOUM,SUDAN. UNIV KHARTOUM,FAC MED,DEPT MED,KHARTOUM,SUDAN. UNIV JUBA,COLL MED,DEPT COMMUNITY MED,JUBA,SUDAN. MINIST HLTH SUDAN,NATL HLTH LAB,DEPT PARASITOL,KHARTOUM,SUDAN. MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824. RP ELTOUM, IA (reprint author), NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. FU PHS HHS [A1 16312-08] NR 23 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD JUL PY 1994 VL 81 IS 7 BP 996 EP 999 DI 10.1002/bjs.1800810722 PG 4 WC Surgery SC Surgery GA NY258 UT WOS:A1994NY25800017 PM 7922096 ER PT J AU CAHN, MA AF CAHN, MA TI PRACTICE GUIDELINES - A PIECE OF THE QUALITY PUZZLE SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the Medical-Library-Association CY MAY 17-18, 1993 CL CHICAGO, IL SP MED LIB ASSOC AB The National Library of Medicine (NLM) librarians provided support to the first thirteen panels sponsored by the Agency for Health Care Policy and Research by conducting literature searches, providing document delivery, and preparing bibliographic databases. Since then, NLM has moved into a consulting role, helping panels link up with local members of the National Network of Libraries of Medicine. NLM staff members have also prepared several documents useful to the development and dissemination of practice guidelines. RP CAHN, MA (reprint author), NATL LIB MED,NATL INFORMAT CTR HLTH SERV RES & HLTH CARE TECHNOL,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1994 VL 82 IS 3 BP 312 EP 314 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA NY668 UT WOS:A1994NY66800011 PM 7920342 ER PT J AU WEXLER, LH HELMAN, LJ AF WEXLER, LH HELMAN, LJ TI PEDIATRIC SOFT-TISSUE SARCOMAS SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article AB Soft tissue sarcomas are the sixth most common cancer in children and collectively account for about seven percent of all pediatric cancers. The development of increasingly intensive, multimodality treatment protocols for these tumors has led to a steady increase in cure rates for these neoplasms, especially for rhabdomyosarcoma, the most common pediatric soft tissue sarcoma. This article provides an overview of the basic biology, clinical management, and clinical research for pediatric soft tissue sarcomas. RP WEXLER, LH (reprint author), NCI,PEDIAT BRANCH,SOLID TUMOR SECT,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 32 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL-AUG PY 1994 VL 44 IS 4 BP 211 EP 247 DI 10.3322/canjclin.44.4.211 PG 37 WC Oncology SC Oncology GA NX276 UT WOS:A1994NX27600003 PM 8019928 ER PT J AU BYRNE, C SMART, CR CHU, KC HARTMANN, WH AF BYRNE, C SMART, CR CHU, KC HARTMANN, WH TI SURVIVAL ADVANTAGE DIFFERENCES BY AGE - EVALUATION OF THE EXTENDED FOLLOW-UP OF THE BREAST-CANCER DETECTION DEMONSTRATION PROJECT SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Breast Cancer CY AUG 26-28, 1993 CL BOSTON, MA SP AMER CANC SOC, AMER ACAD FAMILY PHYSICIANS, AMER COLL OBSTETRICIANS & GYNECOLOGISTS, AMER COLL RADIOL, AMER COLL SURGEONS COMMISS CANC, AMER OSTEOPATH ASSOC, AMER SOC PREVENT ONCOL, NATL ASSOC ONCOL SOCIAL WORKERS, NATL ASSOC SOCIAL WORKERS, ONCOL NURSING SOC, SOC SURG ONCOL DE BREAST CANCER; SURVIVAL; AGE ID WOMEN; MAMMOGRAPHY; GUIDELINES; MORTALITY; WORKSHOP; HEALTH; RISK AB Background. This study considers breast cancer survival patterns by age group among women diagnosed in the Breast Cancer Detection Demonstration Project (BCDDP) to provide insight into the nature of breast cancer and suggest a possible explanation as to why the results of the randomized clinical trials differ for women younger than 50 and those 50 or older. Based on the findings of several randomized clinical trials, there is a general consensus that breast cancer screening provides a significant benefit for women aged 50-69. From these trials, there is little evidence of a short term benefit and uncertainty regarding any long term benefit of mammographic screening for women aged 40-49. Methods. The BCDDP was not a randomized trial, but a nationwide breast cancer screening program conducted between 1973-1980, in which all participants received annual physical and mammographic examinations. Using the BCDDP data, this study calculated 14-year breast survival among 4051 women diagnosed with cancer between 1973 and 1980 and followed through 1988 and 1989. Results. In all, 598 women died of breast cancer, resulting in an overall 14-year breast cancer survival of 83.4% (standard error = 0.007). Breast cancer survival varied by tumor type, lymph node status, tumor size, and stage at diagnosis. For most of the cases, however, both the distribution and breast cancer survival rates were similar for women aged 40-49, 50-59, and 60-69 across all prognostic indicators. Only breast cancer survival among women with invasive breast cancer who had a primary tumor 5 cm or larger or with positive lymph nodes differed by age, with women aged 60-69 at diagnosis having poorer survival. Analyses by modality of detection conducted in a subset of 2739 cases indicated that the 34.6% of the cases detected by mammography alone had the highest overall breast cancer survival rates (90.9%), while the 32.2% of the cases detectable by both physical examination and mammography had the lowest breast cancer survival (79.0%). Overall, women diagnosed with breast cancer in the BCDDP had a survival advantage if diagnosed with either a smaller tumor or no positive lymph nodes, or if their breast cancer was detected by mammography alone. For women with large tumors (greater than or equal to 5 cm), the survival was 80.8% for ages 40-49, 72.1% for ages 50-59, and 61.7% for ages 60-69. Discussion. Due to the higher breast cancer survival rates among women aged 40-49 with poorer prognostic characteristics, the breast cancer survival advantage for having a smaller tumor, no positive lymph nodes, or breast cancer detected by mammography alone was lower for women aged 40-49 than women aged 50 or older at diagnosis. These differences in survival advantage may help to account for the differences in mortality by age in the randomized clinical trials. C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. AMER BOARD PATHOL,TAMPA,FL. RP BYRNE, C (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EPN-443,BETHESDA,MD 20892, USA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 36 TC 33 Z9 33 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1994 VL 74 IS 1 SU S BP 301 EP 310 PG 10 WC Oncology SC Oncology GA NU475 UT WOS:A1994NU47500013 PM 8004601 ER PT J AU HENSON, DE TARONE, RE AF HENSON, DE TARONE, RE TI INVOLUTION AND THE ETIOLOGY OF BREAST-CANCER SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Breast Cancer CY AUG 26-28, 1993 CL BOSTON, MA SP AMER CANC SOC, AMER ACAD FAMILY PHYSICIANS, AMER COLL OBSTETRICIANS & GYNECOLOGISTS, AMER COLL RADIOL, AMER COLL SURGEONS COMMISS CANC, AMER OSTEOPATH ASSOC, AMER SOC PREVENT ONCOL, NATL ASSOC ONCOL SOCIAL WORKERS, NATL ASSOC SOCIAL WORKERS, ONCOL NURSING SOC, SOC SURG ONCOL DE BREAST CANCER; AGING; INVOLUTION; ETIOLOGY ID MAMMOGRAPHIC PARENCHYMAL PATTERNS; ESTROGEN REPLACEMENT THERAPY; RISK-FACTORS; REPRODUCTIVE FACTORS; AGE; FEATURES; BIRTH; 1ST AB Because of the recognized relationship between aging and the development of cancer, the authors have proposed that the rate and extent of involution may be important factors in the etiology of breast cancer. They further have examined existing epidemiologic and histopathologic data to evaluate the possible association between abnormal involution and breast cancer risk. Evidence for the association is largely circumstantial, because studies have not been designed specifically to evaluate the relationship between the process of involution and breast cancer. Until studies are performed to compare histopathologically the extent of involution in breast cancer patients and age-matched controls, the role of involution in the etiology of breast cancer will remain uncertain. C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,ROOM 305,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 43 Z9 43 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 JUL 1 PY 1994 VL 74 IS 1 SU S BP 424 EP 429 PG 6 WC Oncology SC Oncology GA NU475 UT WOS:A1994NU47500028 PM 8004616 ER PT J AU PESATORI, AC SONTAG, JM LUBIN, JH CONSONNI, D BLAIR, A AF PESATORI, AC SONTAG, JM LUBIN, JH CONSONNI, D BLAIR, A TI COHORT MORTALITY AND NESTED CASE-CONTROL STUDY OF LUNG-CANCER AMONG STRUCTURAL PEST-CONTROL WORKERS IN FLORIDA (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE BRAIN CANCER; CASE-CONTROL; COHORT; LUNG CANCER; MALES; MORTALITY; PESTICIDES; UNITED-STATES AB A previous report on the mortality of this cohort of Florida (United States) pest control workers found the risk of lung cancer was positively associated with the number of years licensed. An additional follow-up (1977-82) of this male cohort confirmed the excess (SMR = 1.4) and the rising risk with increasing number of years licensed (SMR = 2.2 among workers employed more than 20 years). A nested case-control study was undertaken to determine the effects of smoking and the type of pesticide exposure on lung cancer risk. Occupational histories and other data were obtained on 65 deceased lung cancer cases, 122 deceased controls, and 172 living controls. Interviews were conducted with next-of-kin regardless of the vital status of the subject. Odds ratios (OR) were adjusted by age and smoking. Adjustments for diet and other occupations had no effect on risk estimates and were not included in the final model. Using information from licensing records, ORs for lung cancer were greater for workers first licensed before age 40 (OR = 2.4, 95 percent confidence interval [CI] = 1.0-5.9 with deceased controls) and increased from 1.4 (CI = 0.7-3.0) for subjects licensed 10-19 years to 2.1 (CI = 0.8-5.5) for subjects licensed 20 or more years. Using living controls, an association with duration of employment was observed when years of licensure were lagged five years, but was not observed in unlagged analyses. Using information from the questionnaire, the risk of lung cancer was greater among those who worked as pest control operators than non-pest control workers. Although numbers were typically small, lung cancer risk among pest control operators was associated with reported exposure to carbamates, organophosphates, and phenoxyacetic acids and more specifically with diazinon, DDT, carbaryl, and pro-poxur. These results further suggest that pesticides may play a role in lung cancer risk and underscore the need for research that focuses on specific chemicals. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892. OI pesatori, angela/0000-0002-0261-3252 NR 0 TC 52 Z9 52 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1994 VL 5 IS 4 BP 310 EP 318 DI 10.1007/BF01804981 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NT975 UT WOS:A1994NT97500002 PM 8080942 ER PT J AU BROWN, LM SILVERMAN, DT POTTERN, LM SCHOENBERG, JB GREENBERG, RS SWANSON, GM LIFF, JM SCHWARTZ, AG HAYES, RB BLOT, WJ HOOVER, RN AF BROWN, LM SILVERMAN, DT POTTERN, LM SCHOENBERG, JB GREENBERG, RS SWANSON, GM LIFF, JM SCHWARTZ, AG HAYES, RB BLOT, WJ HOOVER, RN TI ADENOCARCINOMA OF THE ESOPHAGUS AND ESOPHAGOGASTRIC JUNCTION IN WHITE MEN IN THE UNITED-STATES - ALCOHOL, TOBACCO, AND SOCIOECONOMIC-FACTORS SO CANCER CAUSES & CONTROL LA English DT Article DE ADENOCARCINOMA; ALCOHOL; CASE-CONTROL STUDY; ESOPHAGUS; MALES; SOCIAL CLASS; TOBACCO; ULCER; UNITED-STATES AB In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric (EG) junction, has been increasing rapidly over the past two decades. Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. A population-based case-control interview study of 174 White men with adenocarcinoma of the esophagus and 750 controls living in three areas of the United States offered the opportunity to investigate the relationship of these cancers with smoking, alcohol drinking, socioeconomic factors, and history of ulcer. There were significantly elevated risks for men who smoked cigarettes (odds ratio [OR] = 2.1) or drank liquor (OR = 1.6). For both cigarette smoking and liquor drinking, there were significant dose gradients with amount consumed. No reduction in risk was observed following smoking cessation. Subjects who switched from nonfilter to filter cigarettes experienced half the risk of those who only smoked nonfilter cigarettes. Inverse risk gradients were seen with increasing recent annual income, with the highest risk (OR = 3.4) for the lowest category. The risk for a history of ulcer (OR = 1.7), especially of the duodenum (OR = 2.2), was also significantly elevated. These data suggest that tobacco and alcohol may be etiologic factors for adenocarcinoma of the esophagus and EG junction, but these factors do not appear to explain the rapid rise in incidence of these tumors. The associations with low social class and history of ulcer need to be explored in greater detail along with other factors that may account for the temporal trends in esophageal adenocarcinomas. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51092, N01-CP-51090, N01-CP-51089] NR 0 TC 146 Z9 146 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1994 VL 5 IS 4 BP 333 EP 340 DI 10.1007/BF01804984 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NT975 UT WOS:A1994NT97500005 PM 8080945 ER PT J AU LIEBMANN, J DELUCA, AM COFFIN, D KEEFER, LK VENZON, D WINK, DA MITCHELL, JB AF LIEBMANN, J DELUCA, AM COFFIN, D KEEFER, LK VENZON, D WINK, DA MITCHELL, JB TI IN-VIVO RADIATION PROTECTION BY NITRIC-OXIDE MODULATION SO CANCER RESEARCH LA English DT Note ID CONTROLLED BIOLOGICAL RELEASE; AGENTS; NUCLEOPHILES; COMPLEXES AB Drugs that affect blood flow have been shown to be whole body radiation protectors. Using N-G-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)(2),N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. N-G-Nitro-L-arginine given to mice between 15 and 60 min prior to radiation afforded significant protection from whole body irradiation, e.g., the estimated whole body irradiation dose required to kill 50% of mice by 30 days after radiation (LD(50/30)) in mice treated with N-G-nitro-L-arginine 60 min before irradiation was 1051 cGy compared with a whole body radiation LD(50/30) of 822 cGy in control mice (P < 0.00001). Treatment of mice with DEA/NO prior to whole body irradiation also significantly reduced toxicity; the estimated whole body radiation LD(50/30) was 1063 and 945 cGy in mice treated with DEA/NO 10 or 30 min before irradiation, respectively (P < 0.00001 for radiation LD(50/30) of either DEA/NO-treated group compared with control). Measurement of [C-14]etanidazoIe binding to bone marrow demonstrated that DEG/NO and N-G-nitro-L-arginine exacerbated bone marrow hypoxia. Perturbations of NO levels have profound effects on in vivo radiosensitivity of normal tissues. We hypothesize that alterations in regional blood flow may underlie the changes in radiosensitivity that we have observed. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP LIEBMANN, J (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 20 TC 47 Z9 50 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3365 EP 3368 PG 4 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800010 PM 7516820 ER PT J AU CLARK, HM YANO, T OTSUKI, T JAFFE, ES SHIBATA, D RAFFELD, M AF CLARK, HM YANO, T OTSUKI, T JAFFE, ES SHIBATA, D RAFFELD, M TI MUTATIONS IN THE CODING REGION OF C-MYC IN AIDS-ASSOCIATED AND OTHER AGGRESSIVE LYMPHOMAS SO CANCER RESEARCH LA English DT Note ID GENE-EXPRESSION; DOMAIN; TRANSACTIVATION; TRANSFORMATION; ONCOPROTEIN AB Our previous studies of the translocated MYC gene in Burkitt's lymphoma showed the existence of clustered somatic mutations located in the transcriptional activation domain. We now report that aggressive lymphomas arising in the acquired immunodeficiency syndrome (AIDS) contain similar mutations and that the presence of mutations is correlated with the rearrangement of the oncogene. Mutations were also found in other de novo non-AIDS, non-Burkitt's aggressive lymphomas with MYC rearrangements. An unusual asparagine to serine mutation at codon 11 was identified in several transformed follicular lymphomas without MYC rearrangement but not in normal tissues from patients with this mutation. These findings indicate that AIDS-associated and other de novo aggressive lymphomas with the MYC gene rearrangement are subject to the same mutation and selection process that affects Burkitt's lymphomas. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT PATHOL,LOS ANGELES,CA 90033. NR 22 TC 58 Z9 58 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3383 EP 3386 PG 4 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800015 PM 8012955 ER PT J AU MICHIELI, P CHEDID, M LIN, D PIERCE, JH MERCER, WE GIVOL, D AF MICHIELI, P CHEDID, M LIN, D PIERCE, JH MERCER, WE GIVOL, D TI INDUCTION OF WAF1/CIP1 BY A P53-INDEPENDENT PATHWAY SO CANCER RESEARCH LA English DT Note ID WILD-TYPE P53; PROTEIN; CYCLE; INHIBITOR; KINASES; CANCER; P21 AB The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G, arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 ''knock-out'' mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/ CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/ CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. RP MICHIELI, P (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892, USA. RI Michieli, Paolo/A-2588-2011 FU NCI NIH HHS [CA54140, CA55541] NR 20 TC 882 Z9 895 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3391 EP 3395 PG 5 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800017 PM 8012956 ER PT J AU DANIELPOUR, D KADOMATSU, K ANZANO, MA SMITH, JM SPORN, MB AF DANIELPOUR, D KADOMATSU, K ANZANO, MA SMITH, JM SPORN, MB TI DEVELOPMENT AND CHARACTERIZATION OF NONTUMORIGENIC AND TUMORIGENIC EPITHELIAL-CELL LINES FROM RAT DORSAL-LATERAL PROSTATE SO CANCER RESEARCH LA English DT Article ID METHYL-N-NITROSOUREA; GROWTH FACTOR-BETA; PHENOL-CHLOROFORM EXTRACTION; ANDROGEN RECEPTOR EXPRESSION; LOBUND-WISTAR RATS; SINGLE-STEP METHOD; VENTRAL PROSTATE; ACID-PHOSPHATASE; SERUM-FREE; TESTOSTERONE PROPIONATE AB We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D-3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirements for optimal growth. Growth of NRP-154 cells is stimulated by dexamethasone and insulin, inhibited by transforming growth factor beta 1, but not significantly altered by epidermal growth factor, cholera toxin, dihydrotestosterone, retinoic acid, or 1 alpha,25-dihydroxyvitamin D-3. Our data suggest that the NRP-152 and NRP-154 cell lines are suitable systems for analysis of normal prostate growth and prostatic carcinogenesis. RP DANIELPOUR, D (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. RI Kadomatsu, Kenji/G-8083-2012 NR 53 TC 109 Z9 110 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3413 EP 3421 PG 9 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800021 PM 8012960 ER PT J AU YANAGAWA, Y SAWADA, M DEGUCHI, T GONZALEZ, FJ KAMATAKI, T AF YANAGAWA, Y SAWADA, M DEGUCHI, T GONZALEZ, FJ KAMATAKI, T TI STABLE EXPRESSION OF HUMAN CYP1A2 AND N-ACETYLTRANSFERASES IN CHINESE-HAMSTER CHL CELLS - MUTAGENIC ACTIVATION OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE AND 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE SO CANCER RESEARCH LA English DT Article ID AROMATIC AMINE ACETYLTRANSFERASE; SALMONELLA-TYPHIMURIUM TA98; HUMAN LIVER; METABOLIC-ACTIVATION; ACETYL-COA; HETEROCYCLIC AMINES; O-ACETYLTRANSFERASE; COLORECTAL-CANCER; MOLECULAR-CLONING; COOKED FOODS AB In order to investigate the metabolic activation pathway of food-derived heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), cultured cell lines which stably expressed human cytochrome P4501A2 (CYP1A2) and N-acetyltransferases (NATs) were developed by the method of complementary DNA (cDNA) transfection. First, a cell line expressing CYP1A2, designated A2R-5, was established from the cell line CR-68, which was previously established by introducing NADPH-cytochrome P-450 reductase cDNA into Chinese hamster CHL cells. The expression of CYP1A2 in the transfected cells was confirmed by determining sensitivity to aflatoxin B-1. As the next step, the A2R-5 as well as CR-68 cells were further transfected with human monomorphic NAT (NAT1) or polymorphic NAT (NAT2) cDNAs. The expression of NAT in the transfected cells was confirmed using p-aminobenzoic acid and sulfamethazine as substrates, while no activity was seen in parental CR-68 and A2R-5 cells. The cell line, ANP-25, which expressed both CYP1A2 and NAT2, was approximately 370- and 100-fold more sensitive to IQ and MeIQx, respectively, than parental CR-68 cells in cytotoxicity assays. There were no clear differences in sensitivity to both compounds among CR-68, A2R-5, and the cell lines which expressed NAT1 alone, NAT2 alone, and CYP1A2 plus NAT1. Mutagenicity of IQ and MeIQx at the hypoxanthine guanine phosphori bosyltransferase locus was also detectable only in ANP-25 cells but not in A2R-5 or the cell line expressing CYP1A2 plus NAT1. From these results, it is proposed that both CYP1A2 and NAT2 (but not NAT1) are required for mutagenic activation of these compounds, implying that acetylator polymorphism may be an important risk factor in the carcinogenicity of these compounds. C1 HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB,SAPPORO,HOKKAIDO 060,JAPAN. TOKYO METROPOLITAN INST NEUROSCI,DEPT MOLEC NEUROBIOL,FUCHU,TOKYO 183,JAPAN. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 52 TC 53 Z9 53 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3422 EP 3427 PG 6 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800022 PM 8012961 ER PT J AU CHOE, M WEBBER, KO PASTAN, I AF CHOE, M WEBBER, KO PASTAN, I TI B3(FAB)-PE38(M) - A RECOMBINANT IMMUNOTOXIN IN WHICH A MUTANT FORM OF PSEUDOMONAS EXOTOXIN IS FUSED TO THE FAB FRAGMENT OF MONOCLONAL-ANTIBODY B3 SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN IMMUNOTOXIN; ESCHERICHIA-COLI; MICE; RENATURATION; REGRESSION; LYMPHOMA; SEQUENCE; DOMAINS; CANCER AB Recombinant immunotoxins were made by fusing the Fab domain of monoclonal antibody (MAb) B3 to PE38(M), a truncated mutant form of Pseudomonas exotoxin (PE). The recombinant toxins were made in Escherichia coli by fusing genes encoding the antibody domains to a gene encoding the mutant form of PE. MAI,B3 binds to a carbohydrate antigen found on many kinds of carcinomas. Immunotoxins in which MAb B3 has been chemically coupled to recombinant forms of PE have been shown to be very active cytotoxic agents. PE has also been targeted to tumor cells by replacing the cell-binding domain of PE (domain I) with a single-chain antibody to make a single-chain immunotoxin. In the current study, PE38(M), a mutant form of PE, with a deletion of the cell-binding domain (amino acids 1-252) as well as mutations in domain III and some nonessential sequences in domain Ib (amino acids 365-380), was fused to the light chain of MAb B3. This protein was renatured in the presence of the Fd fragment of MAb B3 to produce a Fab-toxin fusion protein. Alternatively, the Fd fragment of MAb B3 was fused to PE38(M) and combined with the light chain. Both types of B3(Fab)-PE38(M) were just as active on target cells as previously described single-chain immunotoxins. Furthermore, the B3(Fab)-PE38(M) produced complete remissions of human tumor xenografts growing in nude mice. B3(Fab)-PE38(M) has two advantages over single-chain immunotoxins. One is that the yield of recombinant Fab-toxin is very high, with 10-22% of the starting protein recovered as cytotoxically active immunotoxin after chromatographic purification. The second is that the B3(Fab)-PE38(M) has a much longer survival in the circulation of mice with a t(1/2 beta) of similar to 5 h. C1 NCI,DIAG & CTRS,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 26 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3460 EP 3467 PG 8 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800028 PM 8012967 ER PT J AU FRIEDMAN, HS DOLAN, ME KAUFMANN, SH COLVIN, OM GRIFFITH, OW MOSCHEL, RC SCHOLD, SC BIGNER, DD ALIOSMAN, F AF FRIEDMAN, HS DOLAN, ME KAUFMANN, SH COLVIN, OM GRIFFITH, OW MOSCHEL, RC SCHOLD, SC BIGNER, DD ALIOSMAN, F TI ELEVATED DNA-POLYMERASE-ALPHA, DNA-POLYMERASE-BETA, AND DNA TOPOISOMERASE-II IN A MELPHALAN-RESISTANT RHABDOMYOSARCOMA XENOGRAFT THAT IS CROSS-RESISTANT TO NITROSOUREAS AND TOPOTECAN SO CANCER RESEARCH LA English DT Article ID HUMAN OVARIAN-CANCER; CELL-LINE RESISTANT; BIFUNCTIONAL NITROGEN MUSTARDS; HUMAN MEDULLOBLASTOMA; ALKYLATING-AGENTS; MISMATCH REPAIR; TUMOR-CELLS; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; POLY(ADP-RIBOSE) POLYMERASE; CAMPTOTHECIN ANALOG AB Previous investigations have revealed that the human TE-671 MR human rhabdomyosarcoma xenograft selected in vivo for melphalan resistance (M. C. Rosenberg, et al, Cancer Res., 49: 6917-6922, 1989) is cross-resistant to a wide variety of alkylating agents and to bleomycin, but is collaterally sensitive to etoposide. Although glutathione levels were noted to be elevated in TE-671 MR compared to the melphalan-sensitive parental TE-671 xenograft, treatment with buthionine sulfoximine to deplete glutathione levels did not fully restore melphalan sensitivity in the TE-671 MR xenograft. The present studies were undertaken to search for additional mechanisms of resistance in the TE-671 MR xenograft, Drug sensitivity testing performed at the dose of agents that was lethal to 10% of the animals revealed that the TE-671 MR xenograft maintained resistance to the bifunctional cross-linking agent 1,3-bis(2-chloroethyl)-1-nitrosourea and was cross-resistant to the topoisomerase I poison topotecan. Treatment with buthionine sulfoximine did not sensitize the TE-671 MR xenograft to 1,3-bis(2-chloroethyl)-1-nitrosourea. Further, even though O-6-alkylguanine-DNA alkyltransferase levels were high in both the TE-671 and TE-671 MR xenografts, depletion of O-6-alkylguanine-DNA alkyltransferase activity by treatment with O-6-benzylguanine substantially sensitized the TE-671 xenografts but not the TE-671 MR xenografts, suggesting an additional mechanism of resistance. Measurement of additional enzyme activities that might be involved in DNA repair revealed significant elevations in DNA polymerase alpha (46 +/- 8 (SD) units/mg protein in TE-671, 69 +/- 6 units/mg protein in TE-671 MR, P < 0.05) and RNA polymerase beta (0.43 +/- 0.01 units/mg protein in TE-671, 0.78 +/- 0.12 units/mg protein in TE-671 MR, P < 0.05) but not DNA polymerase 6 or total DNA ligase. Examination of topoisomerases by activity assays and Western blotting revealed a 2-fold increase in topoisomerase II and a 2-fold decrease in topoisomerase I in the TE-671 MR xenograft compared to the parental xenograft, apparently explaining the collateral sensitivity to etoposide and cross-resistance to topotecan. These results suggest that TE-671 MR xenografts contain multiple changes in activities of DNA repair-related proteins and other nuclear proteins that could contribute to alkylating agent resistance. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21287. MED COLL WISCONSIN,DEPT BIOCHEM,MILWAUKEE,WI 53226. NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ADV BIOSCI LABS,FREDERICK,MD 21702. SW MED CTR,DEPT NEUROL,DALLAS,TX 75325. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL PEDIAT,HOUSTON,TX 77030. RP FRIEDMAN, HS (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,BOX 2916,DURHAM,NC 27710, USA. FU NIDDK NIH HHS [DK 26912]; NINDS NIH HHS [NS 30245, NS 20023] NR 72 TC 56 Z9 56 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3487 EP 3493 PG 7 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800032 PM 8012971 ER PT J AU CHEN, ZX BREITMAN, TR AF CHEN, ZX BREITMAN, TR TI TRIBUTYRIN - A PRODRUG OF BUTYRIC-ACID FOR POTENTIAL CLINICAL-APPLICATION IN DIFFERENTIATION THERAPY SO CANCER RESEARCH LA English DT Article ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; CANCER CELL-LINE; SODIUM-BUTYRATE; GENE-EXPRESSION; HEXAMETHYLENE BISACETAMIDE; ERYTHROLEUKEMIC CELLS; DIMETHYL-SULFOXIDE; GLOBIN GENES; INDUCTION AB Butyric acid (BA) induces cytodifferentiation in vitro of a wide variety of neoplastic cells. The potential clinical utility of BA is limited by the apparent difficulty of achieving effective concentrations because of its rapid metabolism and short plasma half-life. In this study we addressed two approaches that may achieve effective concentrations of BA in vivo. One strategy is to use BA derivatives as prodrugs that can be metabolized to yield effective BA concentrations in vivo over a sustained period of time. Another strategy is to define agents that are synergistic with BA so that the desired effect can be achieved at lower concentrations of BA. In this study monobutyrin (MB) and tributyrin (TB) were studied in vitro for their effects on inducing differentiation of human myeloid leukemia HL60 cells and murine erythroleukemia cells. On a molar basis TB was about 4-fold more potent than either BA or MB for inducing differentiation of HL60 cells. BA, MB, or TB induced erythroid differentiation of murine erythroleukemia cells. On a molar basis TB was 3- to 4-fold more potent than BA, whereas MB was much less potent than BA. Combinations of all-trans-retinoic acid with either BA, MB, or TB induced myeloid differentiation of HL60 cells synergistically. We saw marked reductions in the doses of each agent that were needed in combination to achieve the same effect as single agents. For example, 130 mu M TB, 110 nM all-trans-retinoic acid, and a combination of 13 mu M TB plus 13 nM all-trans-retinoic acid all induced half-maximal differentiation of HL60 cells. Our results suggest that the readily available TB may be an effective prodrug of BA and may be useful either as a sole agent or in combination with other agents for cytodifferentiation therapy of human malignancies. RP CHEN, ZX (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 47 TC 91 Z9 98 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3494 EP 3499 PG 6 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800033 PM 8012972 ER PT J AU DEBENEDETTI, L SCIALLERO, S GISMONDI, V JAMES, R BAFICO, A BITICCHI, R MASETTI, E BONELLI, L HEOUAINE, A PICASSO, M GRODEN, J ROBERTSON, M RISIO, M CAPRILLI, R BRUZZI, P WHITE, RL ASTE, H SANTI, L VARESCO, L FERRARA, GB AF DEBENEDETTI, L SCIALLERO, S GISMONDI, V JAMES, R BAFICO, A BITICCHI, R MASETTI, E BONELLI, L HEOUAINE, A PICASSO, M GRODEN, J ROBERTSON, M RISIO, M CAPRILLI, R BRUZZI, P WHITE, RL ASTE, H SANTI, L VARESCO, L FERRARA, GB TI ASSOCIATION OF APC GENE-MUTATIONS AND HISTOLOGICAL CHARACTERISTICS OF COLORECTAL ADENOMAS SO CANCER RESEARCH LA English DT Article ID SOMATIC MUTATIONS; POLYPOSIS; IDENTIFICATION; TUMORS; FAP; CHROMOSOME-5Q21; TUMORIGENESIS; CANCER; LOCUS AB Fifty-nine colonic adenomas and 6 hyperplastic colonic polyps were analyzed by single-strand conformation polymorphism analysis for mutations in the adenomatous polyposis coli gene (APC). Frameshifts and premature stop codons in at least one copy of APC were detected in 25 of these adenomas. Five adenomas carried 2 APC mutations. No mutations in APC were found in any of the 6 hyperplastic polyps, The detection of APC mutations increased with size and degree of dysplasia and in rectal as compared to colonic adenomas, although the association was not statistically significant. The frequency of detectable APC mutations was higher in tubulovillous and villous adenomas (10 of 13) than in tubular adenomas (15 of 45) (odds ratio, 6.67; 95% confidence limits, 1.39-41.83; P = 0.005). The significance of the association between the detection of APC mutations and a villous architecture was confirmed in multivariate analysis (relative risk, 6.67; 95% confidence limits, 1.54-28.8; P = 0.005). In conclusion, APC mutation plays a role in adenoma progression; its frequency is significantly higher in lesions with a more villous morphology. C1 NATL CANC INST,I-16132 GENOA,ITALY. UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. UNIV UTAH,HOWARD HUGHES MED INST,DEPT HUMAN GENET,SALT LAKE CITY,UT. OSPED SAN GIOVANNI VECCHIO,DIPARTIMENTO PATOL,TURIN,ITALY. UNIV LAQUILA,DIPARTIMENTO MED INTERNA & SANITA PUBBL,I-67100 LAQUILA,ITALY. OI Bruzzi, Paolo/0000-0002-7874-2077 NR 28 TC 42 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1994 VL 54 IS 13 BP 3553 EP 3556 PG 4 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800043 PM 8012980 ER PT J AU SINGH, J KULKARNI, N KELLOFF, G REDDY, BS AF SINGH, J KULKARNI, N KELLOFF, G REDDY, BS TI MODULATION OF AZOXYMETHANE-INDUCED MUTATIONAL ACTIVATION OF RAS PROTOONCOGENES BY CHEMOPREVENTIVE AGENTS IN COLON CARCINOGENESIS SO CARCINOGENESIS LA English DT Article ID INTERMEDIATE BIOMARKERS; ONCOGENE MUTATIONS; CANCER; TUMORS; RATS; NEOPLASIA; MUCOSA; 1,2-DIMETHYLHYDRAZINE; METHYLAZOXYMETHANOL; TUMORIGENESIS AB In our previous study, we demonstrated that azoxymethane (AOM) treatment significantly enhanced the expression of ras p21, the protein product of ras genes, and that the dietary administration of chemopreventive agents such as D,L-alpha-difluoromethylornithine (DFMO), a irreversible inhibitor of ornithine decarboxylase, and piroxicam, a non-steroidal anti-inflammatory drug (NSAID), exerted a significant inhibitory effect on AOM-induced ras p21 expression. In the present study, which is an extension of our earlier investigation, we have determined the effect of DFMO and piroxicam on mutational activation of ras protooncogenes during AOM-induced colon carcinogenesis. Groups of male F344 rats were fed the modified AIN-76A diet containing 0 or 150 p.p.m. piroxicam, or 4000 p.p.m. DFMO and administered s.c. AOM dissolved in normal saline at a dose rate of 15 mg/kg body wt, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then killed at 0, 4, 16, 24 or 32 weeks after last AOM or saline injection. AOM-induced colon tumors and colonic mucosa from AOM treated as well as saline treated animals were analyzed for point mutations in K- and H-ras protooncogenes by a combination of polymerase chain reaction mediated restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Our results demonstrate that of the total 65 AOM-induced colon tumors analyzed, 45/50 (90%) obtained from AOM-treated animals fed the control diet, 4/11 (36%) from AOM-treated animals fed piroxicam diet, and 1/4 (25%) from AOM-treated animals fed the DFMO diet, contained single-point mutations occurring specifically at the second nucleotide of codon 12 which were identified exclusively as G to A transitions in case of K-ras, and G to A transitions and also G to T transversions in H-ras. similar point mutations were identified in colonic mucosa of 21/30 (70%) of AOM-treated animals fed the control diet, 10/30 (33%) of AOM-treated animals fed piroxicam diet, and none of 30 (0%) of AOM-treated animals fed DFMO diet. These results indicate that the administration of piroxicam and DFMO may inhibit the selective amplification of AOM-induced initiated cells carrying mutated ras genes. Dietary DFMO exerted more pronounced inhibition of selective amplification of initiated cells containing AOM-induced mutant ras. Data suggest that determination of ras activation may be a useful marker for chemoprevention of colon cancer. C1 NCI, DIV CANC PREVENT & CONTROL, CHEMOPREVENT BRANCH, BETHESDA, MD 20892 USA. RP SINGH, J (reprint author), AMER HLTH FDN, DIV NUTR CARCINOGENESIS, 1 DANA RD, VALHALLA, NY 10595 USA. FU NCI NIH HHS [CA-17613, N0-1-CN-85095-03] NR 41 TC 64 Z9 64 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1994 VL 15 IS 7 BP 1317 EP 1323 DI 10.1093/carcin/15.7.1317 PG 7 WC Oncology SC Oncology GA NW755 UT WOS:A1994NW75500004 PM 8033306 ER PT J AU TORTORA, G BUDILLON, A YOKOZAKI, H CLAIR, T PEPE, S MERLO, G ROHLFF, C CHOCHUNG, YS AF TORTORA, G BUDILLON, A YOKOZAKI, H CLAIR, T PEPE, S MERLO, G ROHLFF, C CHOCHUNG, YS TI RETROVIRAL VECTOR-MEDIATED OVEREXPRESSION OF THE RII-BETA SUBUNIT OF THE CAMP-DEPENDENT PROTEIN-KINASE INDUCES DIFFERENTIATION IN HUMAN LEUKEMIA-CELLS AND REVERTS THE TRANSFORMED PHENOTYPE OF MOUSE FIBROBLASTS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MAMMARY EPITHELIAL-CELLS; I REGULATORY SUBUNIT; AMINO-ACID SEQUENCE; ADENOSINE-MONOPHOSPHATE; MOLECULAR-CLONING; HL-60 LEUKEMIA; HUMAN TESTIS; ANTISENSE OLIGODEOXYNUCLEOTIDE; RECEPTOR PROTEINS; GROWTH-INHIBITION AB We have recently shown, using antisense strategy, that the RII beta regulatory subunit of cAMP-dependent protein kinase is essential for cAMP-induced growth inhibition and differentiation of HL-60 human leukemia cells. We constructed a retroviral vector for RII beta (MT-RII beta) by inserting human RII beta complementary DNA into the OT1521 retroviral vector plasmid that contains an internal mouse metallothionein-1 promoter and a neomycin resistance gene. The PA317 packaging cell line was then transfected with MT-RII beta plasmid to produce the amphotrophic stock of MT-RII beta retroviral vector. The infection with MT-RII beta and treatment with CdCl2, brought about growth arrest in HL-60 human leukemia and Ki-ras-transformed NIH 3T3 clone DT tells in monolayer culture with no sign of toxicity. The growth inhibition correlated with the expression of RII beta and accompanied changes in cell morphology; cells became flat, exhibiting enlarged cytoplasm. The growth of these cells in semisolid medium (anchorage-independent growth) was almost completely suppressed. In contrast, overexpression of the Rl alpha subunit of protein kinase enhanced the cell proliferation in DT cells. The MT-RII beta-infected cells exhibited an increased sensitivity toward treatment with cAMP analogues, such as 8-Cl-cAMP and N-6-benzyl-cAMP, as compared with the parental noninfected cells. In MT-RII beta HL-60 cells, N-6-benzyl-cAMP treatment greatly enhanced the expression of monocytic surface markers. These results suggest that the RII beta cAMP receptor, by binding to its ligand, cAMP, acts as a tumor suppressor protein exerting growth inhibition, differentiation, and reverse transformation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892. OI Budillon, Alfredo/0000-0002-6330-6053 NR 31 TC 31 Z9 31 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1994 VL 5 IS 7 BP 753 EP 759 PG 7 WC Cell Biology SC Cell Biology GA NV742 UT WOS:A1994NV74200007 PM 7947390 ER PT J AU TREISMAN, J HWU, P YANNELLI, JR SHAFER, GE COWHERD, R SAMID, D ROSENBERG, SA AF TREISMAN, J HWU, P YANNELLI, JR SHAFER, GE COWHERD, R SAMID, D ROSENBERG, SA TI UP-REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY RETROVIRALLY TRANSDUCED HUMAN TUMOR-INFILTRATING LYMPHOCYTES USING TRANS-RETINOIC ACID SO CELLULAR IMMUNOLOGY LA English DT Article ID THYROID-HORMONE; GENE-TRANSFER; RESPONSE ELEMENTS; RIBONUCLEIC-ACID; MURINE TUMORS; CELL LINES; FACTOR TNF; TRANSCRIPTION; RECEPTORS; IMMUNOTHERAPY AB The ability of retinoic acid (RA) to upregulate gene expression in human tumor-infiltrating lymphocytes (TIL) transduced with a Moloney murine leukemia virus containing the cDNA encoding tumor necrosis factor (TNF) has been studied. TNF production was increased approximately twofold after treatment with RA. This increase was dose dependent and corresponded to a rise in the level of LTR-driven mRNA measured by Northern analysis. RA did not appreciably increase transcription by the SV40 promoter or increase endogenous TNF production. The effect lasted for 3-6 days following withdrawal of RA. These studies indicate that RA can upregulate LTR-driven gene expression in TIL cells bearing retroviral vectors and may thus be of use in studies of the gene therapy of cancer. (C) 1994 Academic Press, Inc. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP TREISMAN, J (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 33 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL PY 1994 VL 156 IS 2 BP 448 EP 457 DI 10.1006/cimm.1994.1189 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NX220 UT WOS:A1994NX22000017 PM 8025957 ER PT J AU LALONDE, RT XIE, S CHAMULITRAT, W MASON, RP AF LALONDE, RT XIE, S CHAMULITRAT, W MASON, RP TI OXIDATION AND RADICAL INTERMEDIATES ASSOCIATED WITH THE GLUTATHIONE CONJUGATION OF MUCOCHLORIC ACID SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Note ID CHLORINE-SUBSTITUTED FURANONES; POTENT BACTERIAL MUTAGEN; DRINKING-WATER; HUMIC-ACID; STEPWISE REMOVAL; N-ACETYLCYSTEINE; BY-PRODUCTS; 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE; 2(5H)-FURANONES; IDENTIFICATION AB The inactivation of the drinking water mutagen mucochloric acid (RICA) by reduced glutathione (GSH) was linked to the formation of an MCA-GSH conjugate, a nonmutagen in the Salmonella typhimurium (TA100) plate incorporation assay. Anaerobic formation of MCA-GSH is found now to be associated with oxidized glutathione (GSSG) and unconverted MCA. The anaerobic reaction of GSH with MCA in the presence of the radical trap 2-methyl-2-nitrosopropane (tNB; ''tert-nitrosobutane'') gives rise to an electron paramagnetic resonance (EPR) resulting from the overlapping spectra of two radical adducts. The first species exhibited hyperfine coupling constants of a(N) = 13.65 G and a(beta)(H) = 0.73 G. The second radical adduct exhibited a three-line signal of a(N) = 12.8 G. The first species is assigned to an adduct of the MCA radical because deuteration of MCA (5-deuterio-MCA) caused the beta-hydrogen hyperfine coupling to collapse. The second radical adduct is unaffected by the deuteration of MCA. Thus, the involvement of both GSSG and a carbon-centered MCA radical in the action of MCA on GSH is indicated. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP LALONDE, RT (reprint author), SUNY COLL ENVIRONM SCI & FORESTRY,DEPT CHEM,SYRACUSE,NY 13210, USA. NR 35 TC 10 Z9 10 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1994 VL 7 IS 4 BP 482 EP 486 DI 10.1021/tx00040a002 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NX673 UT WOS:A1994NX67300002 PM 7981412 ER PT J AU WINK, DA NIMS, RW DARBYSHIRE, JF CHRISTODOULOU, D HANBAUER, I COX, GW LAVAL, F LAVAL, J COOK, JA KRISHNA, MC DEGRAFF, WG MITCHELL, JB AF WINK, DA NIMS, RW DARBYSHIRE, JF CHRISTODOULOU, D HANBAUER, I COX, GW LAVAL, F LAVAL, J COOK, JA KRISHNA, MC DEGRAFF, WG MITCHELL, JB TI REACTION-KINETICS FOR NITROSATION OF CYSTEINE AND GLUTATHIONE IN AEROBIC NITRIC-OXIDE SOLUTIONS AT NEUTRAL PH - INSIGHTS INTO THE FATE AND PHYSIOLOGICAL-EFFECTS OF INTERMEDIATES GENERATED IN THE NO/O-2 REACTION SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ADP-RIBOSYLATION; NITROGEN-DIOXIDE; AQUEOUS-SOLUTION; OXIDATION; CELLS; PEROXYNITRITE; AUTOXIDATION; INHIBITION; SUPEROXIDE AB The critical regulatory function of nitric oxide (NO) in many physiologic processes is well established. However, in an aerobic aqueous environment NO is known to generate one or more reactive and potentially toxic nitrogen oxide (NOx) metabolites. This has led to the speculation that mechanisms must exist in vive by which these reactive intermediates are detoxified, although the nature of these mechanisms has yet to be elucidated. This report demonstrates that among the primary bioorganic products of the reaction of cellular constituents with the intermediates of the NO/O-2 reaction are S-nitrosothiol (S-NO) adducts. Anaerobic solutions of NO are not capable of nitrosating cysteine or glutathione, while S-NO adducts of these amino acids are readily formed in the presence of O-2 and NO. Investigation of the kinetics for the formation of these S-NO adducts has revealed a rate equation of d[RSNO]/dt = k(SNO)[NO](2)[O-2], where k(SNO) = (6 +/- 2) X 10(6) M(-2) s(-1), a value identical to that for the formation of reactive intermediates in the autoxidation of NO. Competition studies performed with a variety of amino acids, glutathione, and azide have shown that cysteine residues have an affinity for the NOx species that is 3 orders of magnitude greater than that of the nonsulfhydryl amino acids, and > 10(6) times greater than that of the exocyclic amino groups of DNA bases. The dipeptide alanyltyrosine reacts with the intermediates of the NO/O-2 reaction with an affinity 150 times less than that of the sulfhydryl-containing compounds. Furthermore, Chinese hamster V79 lung fibroblasts depleted of glutathione display enhanced cytotoxicity on exposure to NO. Together, these results suggest that the S-NO adduct of glutathione may represent a physiological scavenger of NOx species and that enzymes containing cysteine residues critical to their function may be subject to inhibition by reactive intermediates generated in the NO/O-2 reaction. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. INST GUSTAVE ROUSSY,INSERM,U147,RADIOCHIM ADN GRP,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,CNRS,U147,REPARAT LES CHIM & RADIOINDUITES,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,INSERM,U140,F-94805 VILLEJUIF,FRANCE. NCI,RADIAT BIOL BRANCH,RADOBIOL SECT,BETHESDA,MD 20892. RP WINK, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. NR 33 TC 317 Z9 322 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1994 VL 7 IS 4 BP 519 EP 525 DI 10.1021/tx00040a007 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NX673 UT WOS:A1994NX67300007 PM 7981416 ER PT J AU HARGUS, SJ AMOUZEDEH, HR PUMFORD, NR MYERS, TG MCCOY, SC POHL, LR AF HARGUS, SJ AMOUZEDEH, HR PUMFORD, NR MYERS, TG MCCOY, SC POHL, LR TI METABOLIC-ACTIVATION AND IMMUNOCHEMICAL LOCALIZATION OF LIVER PROTEIN ADDUCTS OF THE NONSTEROIDAL ANTIINFLAMMATORY DRUG DICLOFENAC SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CULTURED RAT HEPATOCYTES; ATP-DEPENDENT TRANSPORT; ACYL GLUCURONIDES; COVALENT BINDING; HEPATITIS; BILE; ANTIBODIES; MECHANISM; HEPATOTOXICITY; IDENTIFICATION AB Diclofenac is a nonsteroidal anti-inflammatory agent that is reported to cause serious hepatic injury in some patients. To investigate the possibility that protein adducts derived from reactive intermediates of diclofenac might be responsible for the hepatotoxicity produced by this drug, we recently developed polyclonal antisera that recognized protein adducts of diclofenac. In the present study, we have characterized further the diclofenac adducts in rat liver. Immunoblotting studies showed that diclofenac-labeled hepatic proteins were formed in a dose- and time-dependent manner in rats given diclofenac. Subcellular fractionation of liver homogenates from diclofenac-treated rats showed that a 50-kDa microsomal protein and 110-, 140-, and 200-kDa plasma membrane proteins were labeled preferentially. Immunofluorescence studies of isolated hepatocytes and immunohistochemical analysis of liver slices from diclofenac-treated mice and rats confirmed that plasma membrane proteins were labeled by diclofenac metabolites and showed that the bile canalicular domain of the plasma membrane was a major site of diclofenac adduct formation. Additionally, we found that cytochrome P-450 and UDP-glucuronosyltransferase, but not acyl-CoA synthase, catalyzed the formation of reactive intermediates of diclofenac that were bound covalently to proteins in vitro. The metabolites catalyzed by cytochrome P-450 in vitro were bound exclusively to a 60-kDa microsomal protein, even in the presence of albumin. In contrast, the 110-, 140-, and 200-kDa plasma membrane proteins as well as others appeared to be labeled when diclofenac was activated by UDP-glucuronosyltransferase. Chemical stability studies of the adducts formed in vivo showed that they were unstable under basic conditions and suggested that the metabolites were bound to cellular proteins as ester linkages. These results demonstrated that plasma membrane proteins are major targets of diclofenac metabolites in vivo, and the presence of these adducts may be important in the mechanism of diclofenac hepatotoxicity. C1 GEORGETOWN UNIV,SCH MED,DEPT ANESTHESIA,WASHINGTON,DC 20007. RP HARGUS, SJ (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N104,BETHESDA,MD 20892, USA. NR 45 TC 103 Z9 103 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1994 VL 7 IS 4 BP 575 EP 582 DI 10.1021/tx00040a014 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NX673 UT WOS:A1994NX67300014 PM 7981423 ER EF