FN Thomson Reuters Web of Science™ VR 1.0 PT J AU HOFFMAN, WD NATANSON, C AF HOFFMAN, WD NATANSON, C TI ENDOTOXIN IN SEPTIC SHOCK SO ANESTHESIA AND ANALGESIA LA English DT Review ID TUMOR-NECROSIS-FACTOR; GRAM-NEGATIVE BACTEREMIA; MONOCLONAL ANTIENDOTOXIN ANTIBODIES; ESCHERICHIA-COLI J5; PERMEABILITY-INCREASING PROTEIN; CANINE MODEL; CARDIOVASCULAR DYSFUNCTION; INTRAVENOUS ENDOTOXIN; NORMAL HUMANS; BACTERIAL LIPOPOLYSACCHARIDES C1 UNIV MARYLAND,DEPT ANESTHESIOL,BALTIMORE,MD 21201. RP HOFFMAN, WD (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 98 TC 47 Z9 47 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1993 VL 77 IS 3 BP 613 EP 624 PG 12 WC Anesthesiology SC Anesthesiology GA LW216 UT WOS:A1993LW21600032 PM 8368563 ER PT J AU THOMAS, DA WILLIAMS, GM IWATA, K KENSHALO, DR DUBNER, R AF THOMAS, DA WILLIAMS, GM IWATA, K KENSHALO, DR DUBNER, R TI THE MEDULLARY DORSAL HORN - A SITE OF ACTION OF MORPHINE IN PRODUCING FACIAL SCRATCHING IN MONKEYS SO ANESTHESIOLOGY LA English DT Article DE ANALGESICS, OPIOID, MORPHINE; ANTAGONISTS, OPIOID, NALOXONE; COMPLICATIONS, PRURITUS; NERVE, TRIGEMINAL ID EPIDURAL MORPHINE; INTRATHECAL MORPHINE; PERCEIVED INTENSITY; OBSTETRIC ANALGESIA; OPIATE ANTAGONIST; BETA-ENDORPHIN; NOXIOUS HEAT; HUMAN-SKIN; PRURITUS; FENTANYL AB Background. Pruritus is a common side effect of epidural and intrathecal morphine administration in humans. This naloxone-reversible pruritus is typically present on the trunk, but is often severe around the eyes and nose, of the patients. The brain stem has been proposed as the site where opioids act to produce this effect. The authors studied the effect of morphine administered into the medullary dorsal horn (MDH), the brain stem homologue of the spinal dorsal horn, on facial-scratching behavior in monkeys. Methods: Morphine was unilaterally microinjected into the MDH of rhesus monkeys. Systemic injections of the opioid-receptor antagonist naloxone (0.5 mg/kg intramuscularly) were also made in combination with morphine microinjection. Systemic injections of the antihistamine chlorcyclizine (1.0 and 2.5 mg/kg intramuscularly) were also made to determine if facial scratching was mediated through histamine release. The monkeys were videotaped for 10-15 min before and 1-2 h after opioid microinjection, and the number and location of scratches were counted. Results: A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0.5, 1.0, 2.5, and 5.0 mug). Specificity of the site of action within the MDH was examined by systematically changing the microinjection site, and examining the area of the face that the monkeys scratched. Morphine produced large dose-dependent increases in facial scratching ipsilateral to the microinjection. Increases in facial scratching were also observed contralateral to the microinjections. These effects were reversed by naloxone- The facial area scratched after microinjection of morphine was directly related to the injection site, with 1-mm changes in the location of the microinjection resulting in pronounced changes in the area of the face that the monkeys scratched. Systemic injection of chlorcyclizine produced only a small, transient attenuation of morphine's effect. Conclusions: Data from this study demonstrate that the MDH is a site where morphine acts to produce facial scratching in monkeys by acting at opioid receptors. It is also likely that the MDH is a site where centrally administered opioids act in producing facial pruritus in humans. The effects of morphine on facial-scratching behavior were only modestly attenuated with chlorcyclizine, indicating a minor involvement of a histamine-dependent mechanism of action. RP THOMAS, DA (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,BETHESDA,MD 20892, USA. NR 31 TC 53 Z9 53 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 SEP PY 1993 VL 79 IS 3 BP 548 EP 554 DI 10.1097/00000542-199309000-00019 PG 7 WC Anesthesiology SC Anesthesiology GA LV758 UT WOS:A1993LV75800020 PM 8363081 ER PT J AU HARRIS, B MOODY, E SKOLNICK, P AF HARRIS, B MOODY, E SKOLNICK, P TI SEVOFLURANE AND DESFLURANE MODULATE LIGAND-BINDING AT THE GABA(A) RECEPTOR COMPLEX SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL CRIT CARE,BALTIMORE,MD 21205. NR 1 TC 0 Z9 0 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 SEP PY 1993 VL 79 IS 3A SU S BP A408 EP A408 PG 1 WC Anesthesiology SC Anesthesiology GA LY108 UT WOS:A1993LY10800408 ER PT J AU MEBAZAA, A MAEDA, K MARTIN, LD LAKATTA, EG ROBOTHAM, JL SHAH, AM AF MEBAZAA, A MAEDA, K MARTIN, LD LAKATTA, EG ROBOTHAM, JL SHAH, AM TI ENDOCARDIAL ENDOTHELIAL-CELLS INCREASE CARDIAC MYOCYTE CONTRACTILITY THROUGH THE RELEASE OF ENDOTHELIN SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,PULM ANESTHESIA LAB,BALTIMORE,MD 21205. UNIV WALES COLL MED,CARDIFF CF4 4XN,S GLAM,WALES. NIH,GERONTOL RES CTR,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1993 VL 79 IS 3A SU S BP A636 EP A636 PG 1 WC Anesthesiology SC Anesthesiology GA LY108 UT WOS:A1993LY10800636 ER PT J AU MOODY, E HARRIS, B BASILE, A SKOLNICK, P AF MOODY, E HARRIS, B BASILE, A SKOLNICK, P TI VOLATILE ANESTHETICS ENHANCE [H-3] MUSCIMOL BINDING TO THE GABA(A) RECEPTOR COMPLEX SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL CRIT CARE MED,BALTIMORE,MD 21205. NR 2 TC 0 Z9 0 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 SEP PY 1993 VL 79 IS 3A SU S BP A748 EP A748 PG 1 WC Anesthesiology SC Anesthesiology GA LY108 UT WOS:A1993LY10800748 ER PT J AU SCHAFER, M CARTER, L GOLDBERG, SR STEIN, C AF SCHAFER, M CARTER, L GOLDBERG, SR STEIN, C TI NOVEL MECHANISMS OF PAIN INHIBITION IN INFLAMMATION - CRF AND IL-1-BETA PRODUCE ANALGESIA MEDIATED BY PERIPHERAL OPIOID RECEPTORS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BALTIMORE,MD. NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1993 VL 79 IS 3A SU S BP A903 EP A903 PG 1 WC Anesthesiology SC Anesthesiology GA LY108 UT WOS:A1993LY10800902 ER PT J AU WANDEL, C BOCKER, R BOHRER, H RUGHEIMER, E GONZALEZ, F MARTIN, E AF WANDEL, C BOCKER, R BOHRER, H RUGHEIMER, E GONZALEZ, F MARTIN, E TI MIDAZOLAM IS METABOLIZED BY VARIOUS HUMAN CYTOCHROMES SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 UNIV HEIDELBERG,DEPT ANESTHESIOL,W-6900 HEIDELBERG,GERMANY. UNIV ERLANGEN NURNBERG,DEPT ANESTHESIOL,W-8520 ERLANGEN,GERMANY. UNIV ERLANGEN NURNBERG,DEPT PHARMACOL,W-8520 ERLANGEN,GERMANY. NCI,BETHESDA,MD 20892. NR 4 TC 0 Z9 0 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 SEP PY 1993 VL 79 IS 3A SU S BP A703 EP A703 PG 1 WC Anesthesiology SC Anesthesiology GA LY108 UT WOS:A1993LY10800703 ER PT J AU GUARNACCIA, S KURMAN, CC NOTARANGELO, LD LAGRUTTA, S CANDOTTI, F UGAZIO, AG NELSON, DL BELLANTI, JA AF GUARNACCIA, S KURMAN, CC NOTARANGELO, LD LAGRUTTA, S CANDOTTI, F UGAZIO, AG NELSON, DL BELLANTI, JA TI SERUM-SOLUBLE INTERLEUKIN-2 RECEPTOR (IL-2R) IN CHILDREN WITH ALLERGIC DISORDERS SO ANNALS OF ALLERGY LA English DT Article ID HUMAN IGE SYNTHESIS; ATOPIC-DERMATITIS; T-CELLS; ASTHMA; INDUCTION C1 GEORGETOWN UNIV,SCH MED,DEPT PEDIAT & MICROBIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,INT CTR INTERDISCIPLINARY STUDIES IMMUNOL,WASHINGTON,DC 20007. NCI,IMMUNOPHYSIOL SECT,METAB BRANCH,BETHESDA,MD 20892. UNIV PALERMO,DEPT PEDIAT,I-90134 PALERMO,ITALY. RP GUARNACCIA, S (reprint author), UNIV BRESCIA,DEPT PEDIAT,SPEDALI CIVILI,I-25123 BRESCIA,ITALY. RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Bellanti, Joseph/0000-0002-5038-7202 NR 24 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD SEP PY 1993 VL 71 IS 3 BP 259 EP 262 PG 4 WC Allergy SC Allergy GA LY508 UT WOS:A1993LY50800012 PM 8373000 ER PT J AU BOUMPAS, DT AUSTIN, HA VAUGHAN, EM YARBORO, CH KLIPPEL, JH BALOW, JE AF BOUMPAS, DT AUSTIN, HA VAUGHAN, EM YARBORO, CH KLIPPEL, JH BALOW, JE TI RISK FOR SUSTAINED AMENORRHEA IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS RECEIVING INTERMITTENT PULSE CYCLOPHOSPHAMIDE THERAPY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE AMENORRHEA; LUPUS-ERYTHEMATOSUS; CYCLOPHOSPHAMIDE; AGE FACTORS; DOSE-RESPONSE RELATIONSHIP, DRUG ID DOSE INTRAVENOUS CYCLOPHOSPHAMIDE; PROGRESSIVE MULTIPLE-SCLEROSIS; INDUCED OVARIAN FAILURE; HODGKINS-DISEASE; CONTROLLED TRIAL; FOLLICLE NUMBER; NEPHRITIS; CHEMOTHERAPY; CANCER; WOMEN AB Objective: To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus. Design: Controlled, retrospective clinical study. Setting: Government referral-based research hospital. Patients: Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls. Interventions: Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses. Measurements: Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy. Results: Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: less-than-or-equal-to 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); greater-than-or-equal-to 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients. Conclusions: Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide. C1 NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NIAMS,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892. RP BOUMPAS, DT (reprint author), NIDDK,KIDNEY DIS SECT,BLDG 10,ROOM 3N-112,BETHESDA,MD 20892, USA. NR 42 TC 352 Z9 372 U1 0 U2 4 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 SEP 1 PY 1993 VL 119 IS 5 BP 366 EP 369 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LZ476 UT WOS:A1993LZ47600003 PM 8338289 ER PT J AU RICHARDSON, GE TUCKER, MA VENZON, DJ LINNOILA, RI PHELPS, R PHARES, JC EDISON, M IHDE, DC JOHNSON, BE AF RICHARDSON, GE TUCKER, MA VENZON, DJ LINNOILA, RI PHELPS, R PHARES, JC EDISON, M IHDE, DC JOHNSON, BE TI SMOKING CESSATION AFTER SUCCESSFUL TREATMENT OF SMALL-CELL LUNG-CANCER IS ASSOCIATED WITH FEWER SMOKING-RELATED 2ND PRIMARY CANCERS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE SMOKING CESSATION; CARCINOMA, OAT CELL; LUNG NEOPLASMS; NEOPLASMS, 2ND PRIMARY; SMOKING ID ACUTE NONLYMPHOCYTIC LEUKEMIA; COMBINED MODALITY THERAPY; LONG-TERM SURVIVORS; HODGKINS-DISEASE; COMBINATION CHEMOTHERAPY; BRONCHOGENIC-CARCINOMA; PROGNOSTIC FACTORS; NECK-CANCER; FOLLOW-UP; 10-YEAR EXPERIENCE AB Objective: To determine the incidence of second primary cancers developing in patients surviving free of cancer for 2 or more years after treatment for small-cell lung cancer and to assess the potential effect of smoking cessation. Design: Retrospective review of 540 patients from a single institution with a median follow-up of 6.1 years. Setting. A single government institution (the National Cancer Institute). Patients: Consecutive sample of 540 patients with histologically confirmed small-cell lung cancer treated from 1973 through 1989 on therapeutic clinical trials. Measurements: The relative risk for second primary cancers and death were calculated in patients who remained free of cancer for 2 years after initiation of therapy. The relation of these end points to smoking history was also determined. Results: Fifty-five patients (10%) were free of cancer 2 years after initiation of therapy. Eighteen of these patients developed one or more second primary cancers, including 13 who developed second primary non-small-cell lung cancer. The risk for any second primary cancer compared with that in the general population was increased four times (relative risk, 4.4; 95% CI, 2.5-7.2), with a relative risk of a second primary non-small-cell lung cancer of 16 (CI, 8.4-27). Forty-three patients discontinued smoking within 6 months of starting treatment for small-cell lung cancer, and 12 continued to smoke. In those who stopped smoking at time of diagnosis, the relative risk of a second lung cancer was 11 (CI, 4.4 to 23), whereas, in those who continued to smoke, it was 32 (CI, 12 to 69). Conclusions: Patients with small-cell lung cancer who survive cancer-free for more than 2 years have a significantly increased risk for development of a second primary smoking-related cancer. Cigarette smoking cessation after successful therapy is associated with a decrease in risk for a second smoking-related primary cancer. C1 NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BLDG 8, ROOM 4101, BETHESDA, MD 20899 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. RI Venzon, David/B-3078-2008; Tucker, Margaret/B-4297-2015 NR 77 TC 136 Z9 137 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1993 VL 119 IS 5 BP 383 EP 390 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA LZ476 UT WOS:A1993LZ47600006 PM 8393311 ER PT J AU COHEN, RB FOSS, F AF COHEN, RB FOSS, F TI ANESTHESIA NOT RELATED TO FLUDARABINE TOXICITY - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP COHEN, RB (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1993 VL 119 IS 5 BP 437 EP 437 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LZ476 UT WOS:A1993LZ47600024 ER PT J AU TJULANDIN, SA GARIN, AM MESCHERYAKOV, AA PEREVODCHIKOVA, NI GORBUNOVA, VA SOKOLOV, AV LJUBIMOVA, NV MIRONOVA, GT MOLCHANOV, GV OZOLS, RF HAMILTON, JM AF TJULANDIN, SA GARIN, AM MESCHERYAKOV, AA PEREVODCHIKOVA, NI GORBUNOVA, VA SOKOLOV, AV LJUBIMOVA, NV MIRONOVA, GT MOLCHANOV, GV OZOLS, RF HAMILTON, JM TI CISPLATIN-ETOPOSIDE AND CARBOPLATIN-ETOPOSIDE INDUCTION CHEMOTHERAPY FOR GOOD-RISK PATIENTS WITH GERM-CELL TUMORS SO ANNALS OF ONCOLOGY LA English DT Article DE CHEMOTHERAPY; GERM CELL TUMORS; GOOD PROGNOSIS ID CANCER AB Background: In an attempt to reduce the toxicity of chemotherapy in good-risk testicular cancer patients the two drug combinations, cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC), have been compared. Methods: Good risk was defined according to the MSKCC and IU criteria. 39 Patients have been treated with EP (cisplatin 20 mg/m2 i.v. and etoposide 100 mg/m2 i.v. on days 1 to 5), and 23 patients received EC (carboplatin 350 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 5). Four cycles of chemotherapy were given at 21- and 28-day intervals, respectively, with delays of up to 7 days in istances of leukocyte counts less than 3.0 x 10(9)/l or platelet counts less than 100 x 10(9)/l. Results: In the EP group 34 (87%) of 39 patients achieved CR (26 with chemotherapy alone, 8 with additional surgery). After a median follow-up of 26 (12-58) months 3 (9%) patients relapsed from CR. Currently 38 patients are alive, and 37 (94%) are NED. In the EC group 20 (87%) of 23 patients achieved CR (15 with chemotherapy alone and 5 with additional surgery). After a median follow-up of 45 (26-57) months 6 (30%) patients relapsed from CR. Currently 19 patients are alive and 17 (74%) are NED. There was no difference in survival between the two groups (p = 0.13), but in the EC group the relapse rate was higher (p = 0.052) and the proportion of patients with NED was lower (p = 0.03) in comparison with EP. Toxicity in both groups was mild and similar, but 3 EP-treated patients presented hair loss. Conclusions: The study suggests that carboplatin-etoposide combination therapy is inferior to cisplatin-etoposide in patients with good-risk germ cell tumors. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NCI,BETHESDA,MD 20892. RP TJULANDIN, SA (reprint author), CANC RES CTR AMS RUSSIA,24 KASHIRSKOE SH,MOSCOW 115478,RUSSIA. NR 10 TC 10 Z9 10 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1993 VL 4 IS 8 BP 663 EP 667 PG 5 WC Oncology SC Oncology GA MA364 UT WOS:A1993MA36400008 PM 8240996 ER PT J AU ESPOSITO, M VANNOZZI, MO VIALE, M PELLECCHIA, C MERLO, F CADONI, A CAFAGGI, S PARODI, B LERZA, R POIRIER, MC AF ESPOSITO, M VANNOZZI, MO VIALE, M PELLECCHIA, C MERLO, F CADONI, A CAFAGGI, S PARODI, B LERZA, R POIRIER, MC TI CIS-DIAMMINEDICHLOROPLATINUM(II) - PROCAINE PHARMACOKINETIC INTERACTION IN MICE BEARING P388 LEUKEMIA SO ANTICANCER RESEARCH LA English DT Article DE CIS-DIAMMINEDICHLOROPLATINUM(II); PROCAINE; PHARMACOKINETICS ID CIS-DICHLORODIAMMINEPLATINUM-II; LIPID-PEROXIDATION; LOCAL-ANESTHETICS; CISPLATIN; PLATINUM; HYDROCHLORIDE; TOXICITY; ASCITES; DAMAGE; CANCER AB The distribution and elimination kinetics of cis-diamminedichloroplatinum (II) (DDP) in female BDF1 mice bearing 6-day P388 leukemia were investigated in the presence and absence of procaine hydrochloride (P.HCl) exposure. DDP was administered as a single i.p. dose of 8 mg/kg in a 0.9% NaCl solution 6 days after tumor inoculum. P.HCl was administered as a single i.v. dose of 40 mg/kg immediately after DDP. The combined treatment with P.HCI produced marked changes in the plasma concentration-time profile of Pt. The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP+P.HCl administration. P.HCl treatment induced a significant reduction (P<0.01) in the rate constant of the protein-bound of Pt in plasma of tumored mice. Urinary excretion of Pt was unaffected by P.HCI, and there was no significant P.HCl-induced modification in the concentrations of Pt in the P388 leukemic cells. A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP+P.HCl. A similar reduction was observed in kidneys and testes of tumored mice receiving 16 mg/kg DDP along with 40 mg/kg P.HCl, which also showed lower renal and testicular cisplatin-DNA adducts after DDP+P.HCl than after DDP treatment. Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed. C1 IST NAZL RIC CANC,SERV EPIDEMIOL & BIOSTAT,I-16132 GENOA,ITALY. UNIV GENOA,IST ANAT UMANA,I-16126 GENOA,ITALY. UNIV GENOA,IST TECNOL FARMACEUT & ALIMENTARI,I-16126 GENOA,ITALY. UNIV GENOA,CATTEDRA PATOL MED B,DIPARTIMENTO MED INTERNA,I-16126 GENOA,ITALY. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP ESPOSITO, M (reprint author), IST NAZL RIC CANC,IST,SERV FARMACOL TOSSICOL,VIALE BENEDETTO XU 10,I-16132 GENOA,ITALY. NR 28 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1993 VL 13 IS 5A BP 1511 EP 1516 PG 6 WC Oncology SC Oncology GA MG303 UT WOS:A1993MG30300040 PM 8239529 ER PT J AU SAWAKI, K HIRAMATSU, Y BAUM, BJ AMBUDKAR, IS AF SAWAKI, K HIRAMATSU, Y BAUM, BJ AMBUDKAR, IS TI INVOLVEMENT OF G-ALPHA-Q/11 IN M3-MUSCARINIC-RECEPTOR STIMULATION OF PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE-SPECIFIC PHOSPHOLIPASE-C IN RAT PAROTID-GLAND MEMBRANES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID PROTEIN-ALPHA-SUBUNITS; ACINAR-CELLS; ALPHA-1-ADRENERGIC RECEPTORS; 4,5-BISPHOSPHATE HYDROLYSIS; MUSCARINIC RECEPTOR; CALCIUM ENTRY; SUBSTANCE-P; GQ FAMILY; ACTIVATION; IDENTIFICATION C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM IN-113,BETHESDA,MD 20892. NR 26 TC 38 Z9 38 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 SEP PY 1993 VL 305 IS 2 BP 546 EP 550 DI 10.1006/abbi.1993.1459 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LY022 UT WOS:A1993LY02200047 PM 8396894 ER PT J AU HUANG, KP HUANG, FL CHEN, HC AF HUANG, KP HUANG, FL CHEN, HC TI CHARACTERIZATION OF A 7.5-KDA PROTEIN-KINASE-C SUBSTRATE (RC3 PROTEIN, NEUROGRANIN) FROM RAT-BRAIN SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID CALMODULIN-BINDING PROTEIN; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; IMMUNOCYTOCHEMICAL LOCALIZATION; DEVELOPMENTAL EXPRESSION; PHOSPHORYLATION SITE; NEUROMODULIN GAP-43; CELLULAR SUBSTRATE; IDENTIFICATION; ISOZYMES RP NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. NR 30 TC 77 Z9 83 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP PY 1993 VL 305 IS 2 BP 570 EP 580 DI 10.1006/abbi.1993.1463 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LY022 UT WOS:A1993LY02200051 PM 8080473 ER PT J AU JI, XD JACOBSON, KA AF JI, XD JACOBSON, KA TI SOLUBILIZED RABBIT STRIATAL A2A-ADENOSINE RECEPTORS - STABILITY AND ANTAGONIST BINDING SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID A2 ADENOSINE RECEPTOR; XANTHINE AMINE CONGENER; RAT-BRAIN; AGONIST BINDING; HUMAN-PLATELETS; RADIOLIGAND; A2-RECEPTORS; SEPARATION; LIGAND; SITES C1 NIDDKD,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] NR 32 TC 10 Z9 10 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 SEP PY 1993 VL 305 IS 2 BP 611 EP 617 DI 10.1006/abbi.1993.1469 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LY022 UT WOS:A1993LY02200057 PM 8373201 ER PT J AU ZAHM, SH WEISENBURGER, DD SAAL, RC VAUGHT, JB BABBITT, PA BLAIR, A AF ZAHM, SH WEISENBURGER, DD SAAL, RC VAUGHT, JB BABBITT, PA BLAIR, A TI THE ROLE OF AGRICULTURAL PESTICIDE USE IN THE DEVELOPMENT OF NON-HODGKINS-LYMPHOMA IN WOMEN SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID SOFT-TISSUE SARCOMA; HERBICIDE USE; RISK-FACTORS; EXPOSURE; MORTALITY; MINNESOTA; LEUKEMIA; CANCER; IOWA; MEN AB Non-Hodgkin's lymphoma has been found to be associated with agricultural pesticide use in men, but little is known about the risk in women. In a recent population-based, case-control study conducted in eastern Nebraska, no increased risk of non-Hodgkin's lymphoma was found in women who had ever lived or worked on a farm (odds ratio [OR] = 1.0). Neither the use of insecticides (OR = 0.8) nor herbicides (OR = 0.7) on the farm was associated with non-Hodgkin's lymphoma; however, the number of women who mixed or applied pesticides was small, particularly in comparison to men on farms. Small nonsignificant associations were observed among the women who personally handled insecticides (OR = 1.3) or herbicides (OR = 1.2). Women who personally handled organophosphate insecticides had a significant 4.5-fold increased risk of non-Hodgkin's lymphoma. Use of chlorinated hydrocarbon insecticides was associated with an OR of 1.6; however, the use on dairy cattle was associated with a 3-fold increased risk. Pesticide-related risks were greater among women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives. C1 UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68105. WESTAT CORP,ROCKVILLE,MD. RP ZAHM, SH (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 26 TC 90 Z9 92 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD SEP-OCT PY 1993 VL 48 IS 5 BP 353 EP 358 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA MC454 UT WOS:A1993MC45400011 PM 8215601 ER PT J AU BOUZAS, EA SCOTT, MH MASTORAKOS, G CHROUSOS, GP KAISERKUPFER, MI AF BOUZAS, EA SCOTT, MH MASTORAKOS, G CHROUSOS, GP KAISERKUPFER, MI TI CENTRAL SEROUS CHORIORETINOPATHY IN ENDOGENOUS HYPERCORTISOLISM SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID A BEHAVIOR; PREGNANCY; PATHOGENESIS; MECHANISMS; RESPONSES; CORTISOL; STRESS AB Objective: To examine the potential association of central serous chorioretinopathy with endogenous hypercortisolism (Cushing's syndrome). Designs: Ophthalmologic survey of consecutively admitted patients with endogenous Cushing's syndrome. Setting: An eye clinic of a research center (National Eye Institute, Bethesda, Md). Patients: Sixty consecutive patients with confirmed endogenous Cushing's syndrome. Main Outcome Measures: Findings from complete ophthalmologic evaluation. Results: Three (5%) of 60 patients had one or more episodes of appropriately documented central serous chorioretinopathy. In all cases, the episodes occurred during the period of hypercortisolism. Conclusions: Central serous chorioretinopathy is an uncommon manifestation of endogenous Cushing's syndrome. Since central serous chorioretinopathy has been associated with other hypercortisolemic states, we suggest that glucocorticoids may play a role in the development of this disease. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,10-10N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 33 TC 115 Z9 119 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1993 VL 111 IS 9 BP 1229 EP 1233 PG 5 WC Ophthalmology SC Ophthalmology GA LW463 UT WOS:A1993LW46300020 PM 8363466 ER PT J AU SPERDUTO, RD HU, TS MILTON, RC ZHAO, JL EVERETT, DF CHENG, QF BLOT, WJ BING, L TAYLOR, PR YAO, LJ DAWSEY, S GUO, WD AF SPERDUTO, RD HU, TS MILTON, RC ZHAO, JL EVERETT, DF CHENG, QF BLOT, WJ BING, L TAYLOR, PR YAO, LJ DAWSEY, S GUO, WD TI THE LINXIAN CATARACT STUDIES - 2 NUTRITION INTERVENTION TRIALS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPACITIES CLASSIFICATION-SYSTEM AB Objective: To determine whether the vitamin/mineral supplements used in two cancer intervention trials affected the risk of developing age-related cataracts. Design: Two randomized, double-masked trials with a duration of 5 to 6 years and end-of-trial eye examinations. Settings: Rural communes in Linxian, China. Participants: In trial 1, 2141 participants aged 45 to 74 years, and, in trial 2, 3249 participants aged 45 to 74 years. Interventions: Multivitamin/mineral supplement or matching placebo in trial 1; factorial design to test the effect of four different vitamin/mineral combinations in trial 2 (retinol/zinc, riboflavin/niacin, ascorbic acid/molybdenum, and selenium/alpha-tocopherol/beta carotene). Main Outcome Measures: Prevalence of nuclear, cortical, and posterior subcapsular cataracts in treatment groups at end of trials. Results: In the first trial, there was a statistically significant 36% reduction in the prevalence of nuclear cataract for persons aged 65 to 74 years who received the supplements. In the second trial, the prevalence of nuclear cataract was significantly lower in persons receiving riboflavin/niacin compared with persons not receiving these vitamins. Again, persons in the oldest group, 65 to 74 years, benefited the most (44% reduction in prevalence). No treatment effect was noted for cortical cataract in either trial. Although the number of posterior subcapsular cataracts was very small, there was a statistically significant deleterious effect of treatment with riboflavin/niacin. Conclusions: Findings from the two trials suggest that vitamin/mineral supplements may decrease the risk of nuclear cataract. Additional research is needed in less nutritionally deprived populations before these findings can be translated into general nutritional recommendations. C1 NCI,BETHESDA,MD 20892. BEIJING UNION MED COLL HOSP,BEIJING,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. RP SPERDUTO, RD (reprint author), NEI,BIOMETRY & EPIDEMIOL PROGRAM,BLDG 31,ROOM 6424,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-05634] NR 17 TC 153 Z9 155 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1993 VL 111 IS 9 BP 1246 EP 1253 PG 8 WC Ophthalmology SC Ophthalmology GA LW463 UT WOS:A1993LW46300022 PM 8363468 ER PT J AU SHERN, RJ FOX, PC LI, SH AF SHERN, RJ FOX, PC LI, SH TI INFLUENCE OF AGE ON THE SECRETORY RATES OF THE HUMAN MINOR SALIVARY-GLANDS AND WHOLE SALIVA SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE AGING; MINOR SALIVARY GLANDS; FLOW RATE; WHOLE SALIVA ID FLOW-RATE; GASTROINTESTINAL SYSTEMS; MUCOUS GLANDS; ORAL CAVITY; IMMUNOGLOBULIN; PERFORMANCE; VOLUME; MUCINS; YOUNG; OLD AB This investigation comprised two studies of healthy, unmedicated individuals. The first measured the effect of collection time on the volume of secretions of the minor salivary glands at four specified areas of the lower lip of 13 individuals before and after a mild gustatory stimulus. The second (n = 51) monitored the influence of age and gender on the secretory rates of unstimulated labial, buccal and palatal salivary glands. Also, unstimulated and stimulated flow rates of whole saliva were monitored to provide a point of reference. Volumes of minor gland secretions were measured with a Periotron unit. Results of the first study indicated a linear increase in volumes with collection time (15, 30, 45 and 60 s). Flow rates were similar among the four labial sites, approx. 1 mul/cm2/min, and were not influenced by mild citric acid stimulation. Results of the second study indicated that flow rates differed significantly (p = 0.0001) among the anatomical sites, with similar rates on the right- and left-hand sides. Gender exerted no influence on flow from the minor salivary glands. Similarly, age exerted no influence on flow from the buccal or labial glands. However, the secretory rate for the palatal glands decreased significantly with age (r = -0.44; p < 0.005). As for unstimulated whole saliva, secretory rates were not influenced by age nor gender; rates for stimulated whole saliva increased with age (r = 0.31; p < 0.05). No association was detected between the flow rates of the whole saliva and that of the minor salivary glands. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. NR 54 TC 43 Z9 46 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD SEP PY 1993 VL 38 IS 9 BP 755 EP 761 DI 10.1016/0003-9969(93)90071-S PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LZ641 UT WOS:A1993LZ64100005 PM 8240083 ER PT J AU ANHALT, JP WITEBSKY, FG WOODS, GL AF ANHALT, JP WITEBSKY, FG WOODS, GL TI COLLEGE-OF-AMERICAN-PATHOLOGISTS POSITION STATEMENT REGARDING RAPID DETECTION OF MYCOBACTERIUM-TUBERCULOSIS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material C1 COLL AMER PATHOLOGISTS,ROCHESTER,MN. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. MED COLL PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19129. NR 3 TC 11 Z9 11 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1993 VL 117 IS 9 BP 873 EP 873 PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LW172 UT WOS:A1993LW17200005 PM 8368896 ER PT J AU WOODS, GL WITEBSKY, FG AF WOODS, GL WITEBSKY, FG TI CURRENT STATUS OF MYCOBACTERIAL TESTING IN CLINICAL LABORATORIES - RESULTS OF A QUESTIONNAIRE COMPLETED BY PARTICIPANTS IN THE COLLEGE-OF-AMERICAN-PATHOLOGISTS MYCOBACTERIOLOGY-E SURVEY SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SEPTI-CHEK AFB; DNA PROBES; TUBERCULOSIS; BACTEC; MEDIA; IDENTIFICATION; RECOVERY; SYSTEM; AVIUM; INTRACELLULARE AB To learn what methods are used in clinical microbiology laboratories for detection, identification, and susceptibility testing of mycobacteria, questions addressing these issues were added to the College of American Pathologists' Mycobacteriology E proficiency testing survey, and participants in the survey were asked to complete the questionnaire. Other questions related to numbers of mycobacteriology tests performed and the frequency with which drug-resistant Mycobacterium tuberculosis is isolated. Just over half of the respondents stained smears for acid-fast bacilli with the fluorochrome stain. Only 26% of respondents processed respiratory specimens daily, potentially providing results within 24 hours of receiving the specimen. The most rapid methods currently available for detection of mycobacteria and for identification of M tuberculosis, respectively, were used by 30% and 35% of the respondents. Half of the respondents who performed susceptibility testing on isolates of M tuberculosis used rapid methods. Approximately 26% of the respondents indicated that they usually provided a final identification of M tuberculosis within 21 days of receiving a specimen, and 11% indicated that identification and susceptibility test results were reported within 28 days. Participants' responses indicated that the mean number of specimens received for mycobacterial culture per month was higher during the first 5 months of 1992 than it had been in 1991. Moreover, the number of drug-resistant M tuberculosis isolated per month from January through May 1992 was about double the number isolated per month in 1991. Given the increased incidence of tuberculosis in the United States and the increasing frequency with which drug-resistant M tuberculosis is isolated, use of the most rapid, reliable methods for detection, identification, and susceptibility testing of mycobacteria is recommended. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. RP WOODS, GL (reprint author), MED COLL PENN,DEPT PATHOL & LAB MED,3300 HENRY AVE,PHILADELPHIA,PA 19129, USA. NR 23 TC 30 Z9 30 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1993 VL 117 IS 9 BP 876 EP 884 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LW172 UT WOS:A1993LW17200007 PM 8368898 ER PT J AU THOMAS, RM JAFFE, ES ZARATEOSORNO, A MEDEIROS, LJ AF THOMAS, RM JAFFE, ES ZARATEOSORNO, A MEDEIROS, LJ TI INFLAMMATORY PSEUDOTUMOR OF THE SPLEEN - A CLINICOPATHOLOGICAL AND IMMUNOPHENOTYPIC STUDY OF 8 CASES SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FEATURES; BIOPSY AB We report the clinical, pathologic, and immunophenotypic findings of inflammatory pseudotumors of the spleen in eight patients. The primary importance of recognizing these uncommonly found lesions is to distinguish them from malignant lymphoma, which splenic inflammatory pseudotumors may mimic clinically and radiologically. Grossly, the splenic inflammatory pseudotumors in this study ranged from 0.5 to 11.5 cm. One case was multinodular, and seven lesions were solitary. In general, the size of the lesion correlated with the presence of symptoms. The smaller lesions were usually incidental findings, discovered as part of the workup of idiopathic thrombocytopenic purpura (three cases), during staging for Hodgkin's disease (one case), or at autopsy (one case). Microscopically, the lesions were composed of a variable mixture of inflammatory cells admixed within a spindle cell proliferation. Small, cytologically normal lymphocytes and plasma cells were constant features, in a variable mixture, with neutrophilic and eosinophilic leukocytes present in some cases. Coagulative necrosis was located centrally in six lesions; neutrophilic leukocytes were correlated with the presence of necrosis. The presence of necrosis did not correlate with the presence of symptoms. Immunohistochemical studies revealed that the small lymphocytes present were predominantly T cells. Histiocytes and polytypic plasma cells were also numerous, whereas B cells were infrequent. Inflammatory pseudotumors of the spleen are benign lesions. The clinical follow-up for the seven patients in this study who underwent splenectomy showed no evidence of recurrence or subsequent development of a hematopoietic neoplasm, with a median follow-up of 18 months (range, 3 to 135 months). C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NR 18 TC 75 Z9 80 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1993 VL 117 IS 9 BP 921 EP 926 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LW172 UT WOS:A1993LW17200016 PM 8368906 ER PT J AU BOYLE, L LACK, EE AF BOYLE, L LACK, EE TI SOLITARY CAVERNOUS HEMANGIOMA OF SMALL-INTESTINE - CASE-REPORT AND LITERATURE-REVIEW SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note AB We describe a 14-year-old boy with a solitary cavernous hemangioma in the proximal small intestine that caused recalcitrant iron deficiency anemia beginning at 3 years of age. After a number of attempts to ascertain the cause of the anemia were unsuccessful, the vascular tumor was ultimately diagnosed in the jejunum, approximately 80 cm distal to the ligament of Treitz. We discuss the differential diagnoses of vasoformative intestinal lesions and review the literature on enteric cavernous hemangiomas in childhood. C1 NCI,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. NR 13 TC 33 Z9 39 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1993 VL 117 IS 9 BP 939 EP 941 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LW172 UT WOS:A1993LW17200020 PM 8368910 ER PT J AU EMMERICH, J VERGES, B TAUVERON, I RADER, D SANTAMARINAFOJO, S SCHAEFER, J AYRAULTJARRIER, M THIEBLOT, P BREWER, HB AF EMMERICH, J VERGES, B TAUVERON, I RADER, D SANTAMARINAFOJO, S SCHAEFER, J AYRAULTJARRIER, M THIEBLOT, P BREWER, HB TI FAMILIAL HDL DEFICIENCY DUE TO MARKED HYPERCATABOLISM OF NORMAL APOA-I SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE HYPOALPHALIPOPROTEINEMIA; TANGIER DISEASE; LIPOPROTEINS; METABOLISM; KINETICS; STABLE ISOTOPES ID APOLIPOPROTEIN-A-I; HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; CHOLESTEROL-ACYLTRANSFERASE DEFICIENCY; TANGIER DISEASE; C-III; INVIVO METABOLISM; PREMATURE ATHEROSCLEROSIS; INVITRO CONVERSION; DEUTERATED LEUCINE AB In this article, we describe a 46-year-old man with severe high-density lipoprotein (HDL) deficiency and his kindred. In the proband, HDL cholesterol and apolipoprotein (apo) A-1 levels were 5 and 4.5 mg/dL, respectively. Xanthomata, xanthelasma, arcus corneae, and hepatosplenomegaly were not present. The proband had coronary artery disease, but it was impossible to state whether the HDL deficiency cosegregated with premature coronary artery disease in this kindred. Pedigree analysis was suggestive of a codominant familial disease. Polymerase chain reaction amplification of the apoA-I gene of the proband, followed by subcloning and sequencing, did not reveal any mutation in either the coding regions or intron-exon junctions. A kinetic study using deuterated leucine to endogenously label apoA-1 was performed to elucidate the metabolic basis of the apoA-I deficiency. We demonstrated marked hypercatabolism of apoA-1 in the proband, with a fractional catabolic rate more than 10 times faster than normal; the plasma residence time of apoA-1 in the proband was only 0.38 day compared with 4.10 days in a control subject. The apoA-I production rate was also substantially decreased in the proband. The association of a normal apoA-1 gene sequence with marked hypercatabolism of apoA-1 is similar to that described in Tangier disease. However, except for the presence of mild, diffuse, corneal deposits, this patient had no evidence of the reticuloendothelial cholesterol deposition characteristic of Tangier disease. This study establishes that a form of severe hypoalphalipoproteinemia distinct from Tangier disease can be caused by marked hypercatabolism of a normal A-1 apolipoprotein. C1 HOP ST JACQUES,SERV ENDOCRINOL,CLERMONT FERRAND,FRANCE. RP EMMERICH, J (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,BETHESDA,MD 20892, USA. NR 54 TC 28 Z9 28 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 SEP PY 1993 VL 13 IS 9 BP 1299 EP 1306 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LW352 UT WOS:A1993LW35200006 PM 8364014 ER PT J AU ADAMS, E CHOW, C PREMKUMAR, A PLOTZ, P AF ADAMS, E CHOW, C PREMKUMAR, A PLOTZ, P TI USE OF MAGNETIC-RESONANCE-IMAGING IN MANAGING THE IDIOPATHIC INFLAMMATORY MYOPATHIES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S119 EP S119 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600475 ER PT J AU ALEXANDER, EL RANZENBACH, MR PLITT, JR PATRONAS, N KUMAR, AI AF ALEXANDER, EL RANZENBACH, MR PLITT, JR PATRONAS, N KUMAR, AI TI PERIVENTRICULAR SUBCORTICAL WHITE-MATTER DISEASE - A NEW CAUSE OF CENTRAL-NERVOUS-SYSTEM DISEASE (CNS-D) IN PROBABLE, AS WELL AS DEFINITE, SJOGRENS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MD ANDERSON CANC CTR,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,BALTIMORE,MD 21205. GEORGETOWN UNIV,DEPT RADIOL,WASHINGTON,DC 20007. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S139 EP S139 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600598 ER PT J AU ALEXANDER, EL PLITT, JR KOZACHUK, WE CROWLEY, JS HEYES, MP AF ALEXANDER, EL PLITT, JR KOZACHUK, WE CROWLEY, JS HEYES, MP TI QUINOLINIC ACID (QUIN) - EXCITATORY NEUROTOXIN AND POTENT LIPID PEROXIDANT - A POTENTIAL MEDIATOR OF NEURONAL AND WHITE-MATTER INJURY IN CNS-SS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CARTER WALLACE,PRINCETON,NJ. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,BALTIMORE,MD 21205. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S140 EP S140 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600599 ER PT J AU BARRON, KS CARRINGTON, M REVEILLE, JD ROBINSON, MA AF BARRON, KS CARRINGTON, M REVEILLE, JD ROBINSON, MA TI POLYMORPHISM IN TAP GENES IN REITERS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID,LIG,ROCKVILLE,MD 20852. NCI,PRI,FREDERICK,MD 21702. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S135 EP S135 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600571 ER PT J AU BARRON, KS DEULOFEUT, H REVEILLE, JD ROBINSON, MA AF BARRON, KS DEULOFEUT, H REVEILLE, JD ROBINSON, MA TI T-CELL RECEPTOR (TCR) V-BETA-NULL ALLELES IN JUVENILE RHEUMATOID-ARTHRITIS (JRA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID,LIG,ROCKVILLE,MD 20852. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. NR 0 TC 4 Z9 4 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 SEP PY 1993 VL 36 IS 9 SU S BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600262 ER PT J AU BOLSTER, MB ALLEN, NB HEYES, MP SILVER, RM AF BOLSTER, MB ALLEN, NB HEYES, MP SILVER, RM TI ENHANCEMENT OF THE KYNURENINE PATHWAY OF L-TRYPTOPHAN METABOLISM IN EOSINOPHILIC FASCIITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. DUKE UNIV,DURHAM,NC 27710. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S271 EP S271 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601372 ER PT J AU BOYER, G TEMPLIN, D CORNONIHUNTLEY, J EVERETT, D LAWRENCE, R GORING, W HEYSE, S AF BOYER, G TEMPLIN, D CORNONIHUNTLEY, J EVERETT, D LAWRENCE, R GORING, W HEYSE, S TI SPONDYLOARTHROPATHY IN MEN AND WOMEN - IS THERE A DIFFERENCE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 INDIAN HLTH SERV,ANCHORAGE,AK. UNC,CHAPEL HILL,NC. NIAMS,BETHESDA,MD. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S136 EP S136 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600578 ER PT J AU BOYER, G TEMPLIN, D GORING, W CORNONIHUNTLEY, J EVERETT, D LAWRENCE, R HEYSE, S AF BOYER, G TEMPLIN, D GORING, W CORNONIHUNTLEY, J EVERETT, D LAWRENCE, R HEYSE, S TI DISCREPANCIES BETWEEN PATIENT RECALL AND MEDICAL RECORD - POTENTIAL IMPACT ON CLASSIFICATION AND DIAGNOSIS OF SPONDYLOARTHROPATHY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 INDIAN HLTH SERV,ANCHORAGE,AK. UA,TUCSON,AZ. UNC,CHAPEL HILL,NC. NIAMS,NEI,BETHESDA,NC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S73 EP S73 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600207 ER PT J AU CROFFORD, LJ PILLEMER, SR KALOGERAS, KT CASH, JM MICHELSON, D KLING, MA STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL AF CROFFORD, LJ PILLEMER, SR KALOGERAS, KT CASH, JM MICHELSON, D KLING, MA STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL TI PERTURBATIONS OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION IN PATIENTS WITH FIBROMYALGIA SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010; Crofford, Leslie/J-8010-2013 OI Kling, Mitchel/0000-0002-2232-1409; NR 0 TC 3 Z9 3 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 SEP PY 1993 VL 36 IS 9 SU S BP S220 EP S220 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601072 ER PT J AU CROFFORD, LJ WILDER, RL REMMERS, EF EPPS, HR RISTIMAKI, AP HLA, T AF CROFFORD, LJ WILDER, RL REMMERS, EF EPPS, HR RISTIMAKI, AP HLA, T TI CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 EXPRESSION IN RHEUMATOID SYNOVIAL TISSUES - EFFECTS OF INTERLEUKIN-1-BETA, PHORBOL ESTER, AND CORTICOSTEROIDS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,BETHESDA,MD 20892. AMER RED CROSS,HOLLAND LAB,ROCKVILLE,MD 20855. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S108 EP S108 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600413 ER PT J AU DOHLMAN, J AF DOHLMAN, J TI MULTIVALENT AND CHARGE-RICH SEQUENCE PATTERNS IN SYSTEMIC AUTOANTIGENS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S242 EP S242 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601198 ER PT J AU GOLDMUNTZ, EA WELLS, JR VOGEL, SN KALOGERAS, KT CROFFORD, LJ REMMERS, EF WILDER, RL AF GOLDMUNTZ, EA WELLS, JR VOGEL, SN KALOGERAS, KT CROFFORD, LJ REMMERS, EF WILDER, RL TI HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND CYTOKINE RESPONSES TO LOW-DOSE ENDOTOXIN IN AUTOIMMUNE DISEASE-PRONE LEWIS AND AUTOIMMUNE DISEASE-RESISTANT FISCHER RATS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RI Crofford, Leslie/J-8010-2013 NR 0 TC 1 Z9 1 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 SEP PY 1993 VL 36 IS 9 SU S BP S110 EP S110 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600424 ER PT J AU GRIDLEY, G KLIPPEL, JH HOOVER, RN FRAUMENI, JF AF GRIDLEY, G KLIPPEL, JH HOOVER, RN FRAUMENI, JF TI NON-HODGKINS-LYMPHOMA INCIDENCE AFTER FELTYS-SYNDROME HOSPITALIZATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S87 EP S87 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600288 ER PT J AU HIRSCH, R LETHBRIDGECEIKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD HOCHBERG, MC AF HIRSCH, R LETHBRIDGECEIKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD HOCHBERG, MC TI THE ASSOCIATION OF HAND AND KNEE OSTEOARTHRITIS - EVIDENCE OF A POLYARTICULAR DISEASE SUBSET SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,BETHESDA,MD. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S58 EP S58 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600115 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, C TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, C TOBIN, JD TI THE ASSOCIATION OF OBESITY, FAT DISTRIBUTION AND BODY-COMPOSITION WITH OSTEOARTHRITIS OF THE KNEE - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S234 EP S234 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601154 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD TI BIOCHEMICAL MARKERS OF BONE AND CARTILAGE METABOLISM IN SUBJECTS WITH KNEE OSTEOARTHRITIS - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS HLTH INST,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S206 EP S206 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600990 ER PT J AU HOCHBERG, MC LETHBRIDGECEIKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEIKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD TI THE RELATIONSHIP BETWEEN APPENDICULAR BONE MASS AND OSTEOARTHRITIS OF THE KNEE - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S145 EP S145 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600629 ER PT J AU HOFFMAN, GS LEAVITT, RY KERR, GS ROTTEM, M SNELLER, MC FAUCI, AS AF HOFFMAN, GS LEAVITT, RY KERR, GS ROTTEM, M SNELLER, MC FAUCI, AS TI TREATMENT OF TAKAYASU ARTERITIS WITH METHOTREXATE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 SEP PY 1993 VL 36 IS 9 SU S BP S96 EP S96 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600342 ER PT J AU JACOBSSON, LTH KNOWLER, WC PILLEMER, SR HANSON, RL PETTITT, DJ MCCANCE, DR BENNETT, PH AF JACOBSSON, LTH KNOWLER, WC PILLEMER, SR HANSON, RL PETTITT, DJ MCCANCE, DR BENNETT, PH TI DECREASING INCIDENCE AND PREVALENCE OF RHEUMATOID-ARTHRITIS IN PIMA-INDIANS OVER A 25-YEAR PERIOD - SUPPORT FOR AN ENVIRONMENTAL CAUSE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,PHOENIX,AZ 85014. NIDDK,PHOENIX,AZ 85014. NR 0 TC 1 Z9 1 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 SEP PY 1993 VL 36 IS 9 SU S BP S262 EP S262 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601317 ER PT J AU KATZ, P WHALEN, G KEHRL, JH AF KATZ, P WHALEN, G KEHRL, JH TI CHARACTERIZATION OF A NEW-PROTEIN KINASE PREFERENTIALLY EXPRESSED IN GERMINAL CENTER VERSUS MANTLE ZONE B-LYMPHOCYTES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20007. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S232 EP S232 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601143 ER PT J AU MBAUYA, ALL PLOTZ, PH WILDER, RL MILLER, FW AF MBAUYA, ALL PLOTZ, PH WILDER, RL MILLER, FW TI INCREASED PREVALENCE OF AUTOIMMUNE-DISEASE IN 1ST DEGREE RELATIVES OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. US FDA,CBER,BETHESDA,MD 20014. NR 0 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 SEP PY 1993 VL 36 IS 9 SU S BP S255 EP S255 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601276 ER PT J AU MCINNES, PM SCHUTTINGA, JA SANSLONE, WR STARK, SP KLIPPEL, JH AF MCINNES, PM SCHUTTINGA, JA SANSLONE, WR STARK, SP KLIPPEL, JH TI THE ECONOMIC-IMPACT OF TREATMENT OF SEVERE LUPUS NEPHRITIS WITH PREDNISONE PLUS INTRAVENOUS CYCLOPHOSPHAMIDE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 SEP PY 1993 VL 36 IS 9 SU S BP S65 EP S65 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600161 ER PT J AU MOZAYENI, BR FERRETTI, JA AF MOZAYENI, BR FERRETTI, JA TI MHC-PEPTIDE COMPLEX SYNTHESIS IN-VITRO FOR IMMUNOTHERAPY AND STRUCTURAL STUDIES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S93 EP S93 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600326 ER PT J AU PALIOGIANNI, F VALENTINE, MA BOUMPAS, DT AF PALIOGIANNI, F VALENTINE, MA BOUMPAS, DT TI GLUCOCORTICOIDS (GC) INHIBIT CALCIUM (CA2+)-BUT NOT PROTEIN-KINASE-C (PKC)-DEPENDENT PATHWAYS FOR T-CELL ACTIVATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 3 Z9 3 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 SEP PY 1993 VL 36 IS 9 SU S BP S113 EP S113 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600439 ER PT J AU PALIOGIANNI, F BOUMPAS, DT AF PALIOGIANNI, F BOUMPAS, DT TI CYCLIC-AMP COUNTERACTS CALCINEURIN DEPENDENT PATHWAYS OF T-CELL ACTIVATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S112 EP S112 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600438 ER PT J AU PALLIOGIANNI, F BALOW, JE BOUMPAS, DT AF PALLIOGIANNI, F BALOW, JE BOUMPAS, DT TI GLUCOCORTICOIDS INHIBIT ACCESSORY SIGNALS FOR T-CELL ACTIVATION VIA CD2 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S69 EP S69 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600184 ER PT J AU REVEILLE, JD BARRON, KS CARRINGTON, M AF REVEILLE, JD BARRON, KS CARRINGTON, M TI HLA CLASS-II ALLELES IN CAUCASIANS WITH REITERS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. LIG,NIAID,ROCKVILLE,MD 20852. NCI,PRI,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S135 EP S135 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600572 ER PT J AU RIDER, LG MILLER, FW TARGOFF, IN SAMAYOA, E LINDAHL, M SHERRY, DD WENER, MH PLOTZ, PH AF RIDER, LG MILLER, FW TARGOFF, IN SAMAYOA, E LINDAHL, M SHERRY, DD WENER, MH PLOTZ, PH TI MYOSITIS-SPECIFIC AUTOANTIBODIES (MSA) IN CHILDREN - A BROADENED SPECTRUM OF JUVENILE MYOSITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. US FDA,CBER,WASHINGTON,DC 20204. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 8 Z9 8 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 SEP PY 1993 VL 36 IS 9 SU S BP S258 EP S258 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601295 ER PT J AU ROSS, G SAMMARITANO, LR NASS, R LOCKSHIN, M AF ROSS, G SAMMARITANO, LR NASS, R LOCKSHIN, M TI LEARNING-DISABILITIES IN OFFSPRING OF WOMEN WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CORNELL UNIV,MED CTR,NEW YORK HOSP,HOSP SPECIAL SURG,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 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 SEP PY 1993 VL 36 IS 9 SU S BP S87 EP S87 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600290 ER PT J AU RUBIN, LA SHI, MH KARRASS, L AMOS, CI AF RUBIN, LA SHI, MH KARRASS, L AMOS, CI TI ENDOGENOUS RETROVIRAL GENE ANALYSES IN AUTOIMMUNE RHEUMATIC DISEASE - SEX-SPECIFIC ASSOCIATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TORONTO,TORONTO M5S 1A8,ONTARIO,CANADA. NIAMS,GENET STUDY SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S197 EP S197 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600934 ER PT J AU RUBIN, LA MCDERMOTT, M KASTNER, DL AMOS, CI MCDEVITT, HO HOLLOMAN, JD SCHMIDTWOLF, G SINHA, AA LUNDBERG, AS CASHIN, P MOLLOY, MG KHAN, MA WOLFE, F CLEGG, D WARD, R AF RUBIN, LA MCDERMOTT, M KASTNER, DL AMOS, CI MCDEVITT, HO HOLLOMAN, JD SCHMIDTWOLF, G SINHA, AA LUNDBERG, AS CASHIN, P MOLLOY, MG KHAN, MA WOLFE, F CLEGG, D WARD, R TI THE ROLE OF T-CELL RECEPTOR BETA-CHAIN HAPLOTYPES IN CONFERRING GENETIC SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TORONTO,TORONTO M5S 1A8,ONTARIO,CANADA. NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NATL UNIV IRELAND UNIV COLL CORK,DEPT RHEUMATOL,CORK,IRELAND. CASE WESTERN RESERVE UNIV,DEPT RHEUMATOL,CLEVELAND,OH 44106. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S197 EP S197 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600933 ER PT J AU SHERMAN, J RABEN, N ARGOV, Z NICASTRI, C ADAMS, E PLOTZ, P AF SHERMAN, J RABEN, N ARGOV, Z NICASTRI, C ADAMS, E PLOTZ, P TI THE GENETIC ABNORMALITIES IN PHOSPHOFRUCTOKINASE DEFICIENCY IN ASKENAZI JEWS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S64 EP S64 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600153 ER PT J AU STAFFORD, FJ FLEISHER, TA BROWN, M LEE, G AUSTIN, H BALOW, JE KLIPPEL, JH AF STAFFORD, FJ FLEISHER, TA BROWN, M LEE, G AUSTIN, H BALOW, JE KLIPPEL, JH TI CLINICAL AND BIOLOGICAL EFFECTS OF ANTI-CD5 RICIN A CHAIN IMMUNOCONJUGATE IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 SEP PY 1993 VL 36 IS 9 SU S BP S227 EP S227 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601114 ER PT J AU TILLEY, B ALARCON, G HEYSE, S TRENTHAM, D NEUNER, R CLEGG, D LEISEN, J BUCKLEY, L FOWLER, S PILLEMER, S TUTTLEMAN, M DUNCAN, H AF TILLEY, B ALARCON, G HEYSE, S TRENTHAM, D NEUNER, R CLEGG, D LEISEN, J BUCKLEY, L FOWLER, S PILLEMER, S TUTTLEMAN, M DUNCAN, H TI MINOCYCLINE FOR TREATMENT OF RHEUMATOID-ARTHRITIS - THE MIRA TRIAL EXPERIENCE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HENRY FORD HLTH SCI CTR,SOUTHFIELD,MI 48075. UNIV ALABAMA,BIRMINGHAM,AL 35294. NIAMSD,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. SUNY HLTH SCI CTR BROOKLYN,BROOKLYN,NY 11203. UNIV UTAH,MED CTR,SALT LAKE CITY,UT 84132. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT 05401. NR 0 TC 6 Z9 6 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 SEP PY 1993 VL 36 IS 9 SU S BP S46 EP S46 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600047 ER PT J AU YARBORO, C PUCINO, F WESLEY, R KLIPPEL, J AMANTEA, M AF YARBORO, C PUCINO, F WESLEY, R KLIPPEL, J AMANTEA, M TI ANTIEMETIC EFFICACY OF ORAL DEXAMETHASONE (DMT) AND ONDANSETRON (OND) IN LUPUS NEPHRITIS (LN) PATIENTS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. SUNY Buffalo, BUFFALO, NY 14260 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S228 EP S228 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601123 ER PT J AU STEENBERGEN, C FRALIX, TA MURPHY, E AF STEENBERGEN, C FRALIX, TA MURPHY, E TI ROLE OF INCREASED CYTOSOLIC-FREE CALCIUM-CONCENTRATION IN MYOCARDIAL ISCHEMIC-INJURY SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE CALCIUM; ISCHEMIA; PRECONDITIONING; NMR; STUNNING ID RAT VENTRICULAR MYOCYTES; INFARCT SIZE; K+ CHANNELS; ADENOSINE; CROMAKALIM; HEART; PRETREATMENT; PROTECTION; PINACIDIL; DAMAGE AB Increases in cytosolic free calcium concentration ([Ca2+]I) may play an important role in myocardial ischemic injury. An early effect of the rise in [Ca2+]I may be impaired postischemic contractile function if the ischemic myocardium is reperfused during the reversible phase of ischemic injury; furthermore, if the rise in [Ca2+]i is prolonged, a cascade of events may be initiated which ultimately results in lethal injury. With the development of methods for measuring [Ca2+]I, it has become possible to evaluate directly the role of increased [Ca2+]I in myocardial ischemic injury. Although it has been possible to show that inhibition of the transport processes which contribute to the early rise in [Ca2+]I attenuates stunning and the rise in [Ca2+]I concurrently, if increased [Ca2+]I plays an important role in ischemic injury, then it should be possible to show that interventions which alter the timecourse of ischemic injury also alter the timecourse of the rise in [Ca2+]I in a parallel manner. Recently, considerable effort has been expended to investigate the mechanisms underlying the preconditioning phenomenon, whereby repetitive brief periods of ischemia prior to a sustained period of ischemia protects the myocardium from injury during the sustained period of ischemia, and this has stimulated additional work to understand the possible involvement of adenosine as a mediator of preconditioning as well as to understand the protective effects of adenosine. Measurements of [Ca2+]I using 19F NMR of 5FBAPTA-loaded hearts have shown that preconditioning attenuates the rise in [Ca2+]I during 30 min of ischemia and reduces stunning during reflow. Adenosine pretreatment mimics the effects of preconditioning on the rise in [Ca2+]I and on stunning, but adenosine receptor antagonists do not eliminate the protective effects of preconditioning, although some adenosine antagonists also block hexose transport and under these conditions, the ability of preconditioning to attenuate the rise in [Ca2+]I is abolished and there is a corresponding loss of the protective effect of preconditioning on stunning. Although it has been suggested that the beneficial effect of preconditioning on infarct size can be eliminated by pretreatment with glibenclamide, in the isolated rat heart glibenclamide does not affect the attenuation of the rise in [Ca2+]I induced by preconditioning and does not affect stunning. All of these studies show a consistent relationship between the magnitude of the rise in [Ca2+]I during ischemia and the degree of stunning during reperfusion. The data suggest that increased [Ca2+]I plays a very important role in myocardial ischemic injury. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP STEENBERGEN, C (reprint author), DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3712,DURHAM,NC 27710, USA. FU NHLBI NIH HHS [R01 HL039752] NR 35 TC 82 Z9 82 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI BERLIN 33 PA C/O SPRINGER-VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD SEP-OCT PY 1993 VL 88 IS 5 BP 456 EP 470 DI 10.1007/BF00795412 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ML638 UT WOS:A1993ML63800009 PM 8117251 ER PT J AU ROBINSON, DL COWIE, RJ AF ROBINSON, DL COWIE, RJ TI ATTENTIONAL ENGAGEMENT AND THE PULVINAR SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID VISUAL SPATIAL ATTENTION; RECEPTIVE-FIELDS; MONKEY; MODULATION; RESPONSES; NEURONS; LESIONS; CORTEX C1 HOWARD UNIV,COLL MED,DEPT ANAT,WASHINGTON,DC 20059. RP ROBINSON, DL (reprint author), NEI,SENSORIMOTOR RES LAB,VISUAL BEHAV SECT,BLDG 10,ROOM 10C101,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1993 VL 16 IS 3 BP 586 EP 587 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA LX954 UT WOS:A1993LX95400089 ER PT J AU COLE, ES LEE, K LAUZIERE, K KELTON, C CHAPPEL, S WEINTRAUB, B FERRARA, D PETERSON, P BERNASCONI, R EDMUNDS, T RICHARDS, S DICKRELL, L KLEEMAN, JM MCPHERSON, JM PRATT, BM AF COLE, ES LEE, K LAUZIERE, K KELTON, C CHAPPEL, S WEINTRAUB, B FERRARA, D PETERSON, P BERNASCONI, R EDMUNDS, T RICHARDS, S DICKRELL, L KLEEMAN, JM MCPHERSON, JM PRATT, BM TI RECOMBINANT HUMAN THYROID-STIMULATING HORMONE - DEVELOPMENT OF A BIOTECHNOLOGY PRODUCT FOR DETECTION OF METASTATIC LESIONS OF THYROID-CARCINOMA SO BIO-TECHNOLOGY LA English DT Article ID HAMSTER OVARY CELLS; ASPARAGINE-LINKED OLIGOSACCHARIDES; PITUITARY GLYCOPROTEIN HORMONES; COMPLEMENTARY DEOXYRIBONUCLEIC-ACID; THYROTROPIN BETA-SUBUNIT; SIALYLATED OLIGOSACCHARIDES; BOVINE THYROTROPIN; ALPHA-SUBUNIT; BIOACTIVITY; LUTROPIN AB We have genetically engineered a cell line, and developed a reproducible process, for the expression and purification of biologically active recombinant human thyroid stimulating hormone (rhTSH). rhTSH was expressed by co-transfecting a human alpha-subunit cDNA with a human beta-subunit partial genomic clone into Chinese Hamster Ovary (CHO) cells. Stable transfectants which expressed high levels of rhTSH were selected, and subsequently cultured on microcarrier beads. The rhTSH-containing media, produced under serum-free conditions, was clarified and purified by a combination of ion exchange, dye and gel filtration chromatographies. Individual step recoveries were greater than 90% with the exception of a very conservative pooling of the final gel filtration step (78% recovery) that resulted in a cumulative yield of 54% for the purification process. Purity of the final bulk material was judged to be > 99% by SDS polyacrylamide gel electrophoresis (SDS-PAGE), reverse phase HPLC, and size exclusion chromatography. Initial characterization of the oligosaccharide composition indicated the presence of partially sialylated bi- and triantenary complex oligosaccharides. Purified rhTSH was active in a thyroid membrane bioactivity assay with a specific activity of 8.2 IU/mg. The in vivo activity of rhTSH in cynomolgus monkeys appeared to be equal to or greater than that reported for bovine TSH (bTSH) in human subjects. The rapid clearance phase half-life of rhTSH was approximately 35 minutes while the post-distribution phase half life was approximately 9.8 hours. Furthermore, the monkeys showed cumulative increases in minimum plasma rhTSH levels when given three daily intramuscular (IM) rhTNH injections; a phenomenon not observed when bTSH had been administered to humans. The rhTSH showed no evidence of toxic or adverse effects when administered at doses up to 7.2 IU/kg and 0.52 IU/kg in rat and monkey, respectively. These are 50X and 4X multiples of the bTNH doses of 0.143 IU/kg (10 IU/70kg) previously administered to humans. C1 BASF,CAMBRIDGE,MA. ARES ADV TECHNOL,RANDOLPH,MA. DIACRIN INC,BOSTON,MA. NIH,BETHESDA,MD 20892. HAZLETOWN WISCONSIN INC,MADISON,WI 53704. RP COLE, ES (reprint author), GENZYME CORP,DEPT THERAPEUT PROT DEV,1 MT RD,FRAMINGHAM,MA 01701, USA. NR 57 TC 75 Z9 75 U1 1 U2 2 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 SEP PY 1993 VL 11 IS 9 BP 1014 EP 1024 DI 10.1038/nbt0993-1014 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA LU957 UT WOS:A1993LU95700020 PM 7764071 ER PT J AU EVANS, GA HOWARD, OMZ ERWIN, R FARRAR, WL AF EVANS, GA HOWARD, OMZ ERWIN, R FARRAR, WL TI INTERLEUKIN-2 INDUCES TYROSINE PHOSPHORYLATION OF THE VAV PROTOONCOGENE PRODUCT IN HUMAN T-CELLS - LACK OF REQUIREMENT FOR THE TYROSINE KINASE LCK SO BIOCHEMICAL JOURNAL LA English DT Note ID RECEPTOR BETA-CHAIN; GTPASE-ACTIVATING PROTEIN; COLONY-STIMULATING FACTOR; HUMAN IL-2 RECEPTOR; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; GROWTH-HORMONE; PROLACTIN; DOMAIN AB The haematopoietic protein, p95vav, has been shown to be a tyrosine kinase substrate and to have tyrosine kinase-modulated guanine-nucleotide-releasing-factor activity. This implies a function in the control of ras or ras-like proteins. Because ras activation has been shown to be a downstream event following stimulation of the interleukin-2 (IL-2) receptor, we investigated the possibility that vav was involved in IL-2 signal transduction pathways, using human T cells as a model. We found rapid tyrosine phosphorylation of vav in response to IL-2 within 1 min, with maximum increase of phosphorylation of 5-fold occurring by 5 min after treatment in normal human T cells. IL-2 stimulation of the human T-cell line YT and a subclone of the YT cell line (YT(lck-)) that does not express message for the src-family kinase p56lck also results in a rapid rate of tyrosine phosphorylation of vav of more than 5-fold by 5 min. These results suggest that vav may play an important role in IL-2-stimulated signal transduction and that there is not a strict requirement for the tyrosine kinase p56lck. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,CYTOKINE MECHANISM SECT,FREDERICK,MD 21702. RP EVANS, GA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 39 TC 60 Z9 60 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 SEP 1 PY 1993 VL 294 BP 339 EP 342 PN 2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LX335 UT WOS:A1993LX33500005 PM 7690544 ER PT J AU WELCH, RW BERGSTEN, P BUTLER, JD LEVINE, M AF WELCH, RW BERGSTEN, P BUTLER, JD LEVINE, M TI ASCORBIC-ACID ACCUMULATION AND TRANSPORT IN HUMAN FIBROBLASTS SO BIOCHEMICAL JOURNAL LA English DT Article ID CHROMAFFIN GRANULES; HUMAN-NEUTROPHILS; HEXOSE-TRANSPORT; INSITU KINETICS; CELLS; CYTOCHALASIN; INHIBITION; GLUCOSE; SYSTEMS; ENZYME AB As the initial step in the use of fibroblasts as a model system for 'in situ kinetics', ascorbic acid (vitamin C) accumulation in normal human fibroblasts was investigated for the first time. Ascorbic acid was transported into fibroblasts and accumulated against a concentration gradient up to 20-fold, as measured by h.p.l.c. with coulometric electrochemical detection. Ascorbic acid accumulation was mediated by two concentration-dependent transport activities. The first was a high-affinity activity with an apparent K(m) of 6 muM and an apparent V(max) of 203 muM/h, and the second was a low-affinity activity with an apparent K(m) of 5 mM and an apparent V(max) of 1.8 mM/h. Both activities were inhibited by metabolic inhibitors and inhibitors of ascorbic acid transport in human neutrophils. The low-affinity transporter could not be accounted for by diffusion. Although the high-affinity transport activity was comparable with that described for human neutrophils, the low-affinity transporter was different. These data provide the first evidence that two-component ascorbic acid transport may be a generalized mechanism for accumulation of this vitamin in humans. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 29 TC 59 Z9 60 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 SEP 1 PY 1993 VL 294 BP 505 EP 510 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LX335 UT WOS:A1993LX33500029 PM 8373364 ER PT J AU GOLDFARB, I KORZEKWA, K KRAUSZ, KW GONZALEZ, F GELBOIN, HV AF GOLDFARB, I KORZEKWA, K KRAUSZ, KW GONZALEZ, F GELBOIN, HV TI CROSS-REACTIVITY OF 13 MONOCLONAL-ANTIBODIES WITH 10 VACCINA CDNA EXPRESSED RAT, MOUSE AND HUMAN CYTOCHROME-P450S SO BIOCHEMICAL PHARMACOLOGY LA English DT Note ID LIVER CYTOCHROME-P-450; CYTOCHROMES-P-450; METABOLISM; TISSUES AB Twelve monoclonal antibodies (MAbs) to rat cytochrome P450s and one MAb to a scup (fish) P450 have been isolated, characterized, and are currently in common use. Expression of cDNAs for different P450s from a vaccinia vector offers a rapid and simple way toward the production of individual P450s. The thirteen MAbs were examined for their cross-reactivity with ten cDNA expressed human, rat, and mouse P450s. Three MAbs to rat 1A1 and fish 1A1 cross-reacted with cDNA expressed mouse 1A1. One of the latter MAbs, 1-7-1 but none of the others cross-reacted with mouse 1A2. Surprisingly, the fish MAb to 1A1 also cross-reacted with human 2E1. Two MAbs to rat 2B1/2B2 cross-reacted with rat 2A1. An MAb to rat 2C11 cross-reacted with human 2C9. Two MAbs to rat 2E1 cross-reacted with human 2E1. Finally, two MAbs to rat 3A1 cross-reacted strongly with human 3A4. These studies open the door to constructing a library of MAbs with defined binding activity to the P450s of human and other species. C1 NCI,MOLEC CARCINOGENESIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 14 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1993 VL 46 IS 5 BP 787 EP 790 DI 10.1016/0006-2952(93)90485-F PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LX648 UT WOS:A1993LX64800002 PM 8373431 ER PT J AU NERURKAR, PV PARK, SS THOMAS, PE NIMS, RW LUBET, RA AF NERURKAR, PV PARK, SS THOMAS, PE NIMS, RW LUBET, RA TI METHOXYRESORUFIN AND BENZYLOXYRESORUFIN - SUBSTRATES PREFERENTIALLY METABOLIZED BY CYTOCHROME-P4501A2 AND CYTOCHROME-2B, RESPECTIVELY, IN THE RAT AND MOUSE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID PHENACETIN O-DEETHYLASE; BIPHENYL-TREATED RATS; MONOCLONAL-ANTIBODIES; LIVER-MICROSOMES; IMMUNOCHEMICAL QUANTITATION; HEPATIC CYTOCHROME-P-450C; CARCINOGENIC ARYLAMINES; FLUOROMETRIC ASSAY; MESSENGER-RNA; INDUCTION AB The cytochrome P450 isozyme specificity for the O-dealkylation of methoxyresorufin (MTR) and benzyloxyresorufin (BZR) in the rat and mouse was investigated. The induction of various alkoxyresorufin O-dealkylation activities was measured in male F344/NCr rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3,4,5,3',4',5'-hexachlorobiphenyl. MTR and ethoxyresorufin (ETR) O-dealkylation activities were induced 30- and 80-fold, respectively, in the liver. ETR O-dealkylation activity was induced > 250-fold in the kidney, whereas the metabolism of MTR was induced only 30-fold in this extrahepatic tissue. Phenacetin, a fairly specific CYP1A2 inhibitor, caused concentration-dependent competitive inhibition of MTR O-dealkylation (k(i) approximately 20 muM at 0.5 muM substrate) in hepatic microsomes from 3,4,5,3',4',5'-hexachlorobiphenyl-treated rats. The corresponding k(i) for inhibition of ETR O-dealkylation by phenacetin was greater-than-or-equal-to 333 muM at a 0.5 muM substrate concentration. A monoclonal antibody displaying inhibitory activity against rat CYP1A1 inhibited ETR O-dealkylation activity, whereas it failed to inhibit MTR O-dealkylation activity. In contrast, a monoclonal antibody reactive with both CYP1A1 and CYP1A2 inhibited both O-dealkylation activities to an equal extent. Similar experiments, employing phenacetin or specific monoclonal antibodies, yielded comparable results when performed with mouse microsomes. The maximal induction of MTR O-dealkylation activity in mice was > 100-fold. The P450 isozyme specificity of BZR O-dealkylation was also examined in both rats and mice. Pregnenolone-alpha-carbonitrile, a strong inducer of CYP3A, only weakly induced BZR O-dealkylation activity. In addition, a monoclonal antibody that specifically inhibits CYP2B caused inhibition of BZR metabolism in microsomes from phenobarbital- or dexamethasone-pretreated rats. In B6C3F1 mice exposed to dietary Aroclor 1254, significant induction of hepatic MTR I-dealkylation activity was observed at concentrations lower than those required for the induction of ETR or BZR O-dealkylation. In summary, it would appear that MTR is a relatively specific substrate for CYP1A2 activity in rodents, while BZR appears to be relatively specific for CYP2B. C1 RUTGERS UNIV,COLL PHARM,PISCATAWAY,NJ 08855. RP NERURKAR, PV (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 38 TC 214 Z9 218 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1993 VL 46 IS 5 BP 933 EP 943 DI 10.1016/0006-2952(93)90504-P PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LX648 UT WOS:A1993LX64800021 PM 8373445 ER PT J AU CHEN, TT SIMON, R AF CHEN, TT SIMON, R TI A MULTIPLE-STEP SELECTION PROCEDURE WITH SEQUENTIAL PROTECTION OF PREFERRED TREATMENTS SO BIOMETRICS LA English DT Article DE BINOMIAL DATA; MANY-ONE TEST; MULTIPLE COMPARISONS; MULTIPLE-STEP SELECTION PROCEDURE; NORMAL DATA; SAMPLE SIZE; SELECTION; SURVIVAL ID CLINICAL-TRIALS; DURATION AB Dunnett (1955, Journal of the American Statistical Association 50, 1096-1121) proposed a one-step many-one test to compare several experimental treatment means with a control. However, after the control treatment is rejected, one would want to make comparisons among the experimental treatments. We assume that there is an order of decreasing preference among the experimental treatments based on other considerations. We propose in this paper a multiple-step selection procedure, an extension of Dunnett's one-step many-one test that will give protection to the preferred treatments and guarantee a high selection probability of the correct treatment when that selection is appropriate. We also provide methods to calculate the sample size required to carry out this test for normal, binomial, and exponential data with random censoring. RP CHEN, TT (reprint author), NCI, BIOMETR RES BRANCH, EXECUT PLAZA N, ROOM 739, BETHESDA, MD 20892 USA. NR 23 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 1993 VL 49 IS 3 BP 753 EP 761 DI 10.2307/2532196 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LZ592 UT WOS:A1993LZ59200008 PM 8241371 ER PT J AU BRITTAIN, EH BAILEY, KR AF BRITTAIN, EH BAILEY, KR TI OPTIMIZATION OF MULTISTAGE TESTING TIMES AND CRITICAL-VALUES IN CLINICAL-TRIALS SO BIOMETRICS LA English DT Article DE CLINICAL TRIALS; INTERIM ANALYSES AB Optimal critical values and times of intermediate testing points are determined to minimize expected sample size in a variety of situations. Two-stage and three-stage models are considered for a variety of values of power. We investigate the robustness of the optimality parameters. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. MAYO CLIN,MED RES STAT,ROCHESTER,MN 55901. NR 8 TC 12 Z9 12 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1993 VL 49 IS 3 BP 763 EP 772 DI 10.2307/2532197 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LZ592 UT WOS:A1993LZ59200009 PM 8241372 ER PT J AU CARR, GJ PORTIER, CJ AF CARR, GJ PORTIER, CJ TI AN EVALUATION OF SOME METHODS FOR FITTING DOSE-RESPONSE MODELS TO QUANTAL-RESPONSE DEVELOPMENTAL TOXICOLOGY DATA SO BIOMETRICS LA English DT Article DE BOOTSTRAP; EXTRA-BINOMIAL VARIABILITY; JACKKNIFE; QUASI-LIKELIHOOD; TERATOLOGY ID LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; TERATOLOGY; REGRESSION; OUTCOMES AB The analysis of quantal-response developmental toxicology data by dose-response modeling is discussed, with emphasis on methods that avoid exact distributional assumptions. These methods (quasi-likelihood, bootstrapping, and jackknifing) are contrasted with analyses based on the beta-binomial distribution. For the resampling procedures, dose-response models are fit under a binomial likelihood. A justification for this choice of estimator in resampling plans is given, based on an extension of the standard results for asymptotic normality and consistency of maximum likelihood estimators. This justification depends only on the true distribution of the data having the usual binomial expectation. A quasi-likelihood approach is also considered, in which simple assumptions about the intralitter correlation structure are made. Quasi-likelihood methods are in theory asymptotically robust to misspecification of the intralitter correlation structure. The practical implications of these asymptotic results are evaluated in a simulation study. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP CARR, GJ (reprint author), PROCTER & GAMBLE CO,REGULATORY & CLIN DEV,DEPT BIOMETR & STAT SCI,11370 REED HARTMAN HIGHWAY,CINCINNATI,OH 45241, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 70 TC 26 Z9 26 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1993 VL 49 IS 3 BP 779 EP 791 DI 10.2307/2532199 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LZ592 UT WOS:A1993LZ59200011 PM 8241373 ER PT J AU MEIER, KL BAILER, AJ PORTIER, CJ AF MEIER, KL BAILER, AJ PORTIER, CJ TI A MEASURE OF TUMORIGENIC POTENCY INCORPORATING DOSE-RESPONSE SHAPE SO BIOMETRICS LA English DT Article DE CARCINOGENICITY STUDIES; CARCINOGENIC POTENCY; INTERCURRENT MORTALITY; RISK ASSESSMENT; SURVIVAL ANALYSIS; TD50; TUMOR INCIDENCE ID ANIMAL CARCINOGENESIS EXPERIMENTS; HAZARDS; CHEMICALS; MORTALITY; MODELS; TESTS; TD50 AB Many researchers have considered the problem of ranking chemical agents based on their carcinogenic potency. Sawyer et al. (1984, Biometrics 40, 27-40) proposed a carcinogenic potency estimate that incorporates both intercurrent mortality and background tumor rates. Since then, many authors have either generalized the method outlined by Sawyer et al. or developed their own method based on a slightly different adjustment for treatment-related changes in survival. None of these methods, however, has estimated the shape of the dose-response curve and incorporated such an estimate in potency estimation. In this manuscript, a measure of tumorigenic potency is proposed that utilizes the estimated shape of the dose-response relationship, in addition to estimated dose effects, in order to rank chemicals on the basis of carcinogenic risk. Comparison of this new measure to that of Sawyer et al. is done using a large database of animal carcinogenicity experiments from the National Cancer Institute and the National Toxicology Program. C1 NIEHS,RISK METHODOL SECT,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. MIAMI UNIV,DEPT MATH & STAT,OXFORD,OH 45056. NIOSH,DIV STAND DEV & TECHNOL TRANSFER,CINCINNATI,OH 45266. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 25 TC 11 Z9 11 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1993 VL 49 IS 3 BP 917 EP 926 DI 10.2307/2532213 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LZ592 UT WOS:A1993LZ59200025 PM 8241378 ER PT J AU KORN, EL AF KORN, EL TI ON ESTIMATING THE DISTRIBUTION FUNCTION FOR QUALITY-OF-LIFE IN CANCER CLINICAL-TRIALS SO BIOMETRIKA LA English DT Article DE INFORMATIVE CENSORING; KAPLAN-MEIER ESTIMATOR; QUALITY OF LIFE; REPEATED MEASURES; SURVIVAL ANALYSIS AB The analysis of quality-of-life data collected at periodic intervals in a cancer clinical trial must account for those patients' data that are 'missing' because of death or administrative censoring. We examine estimates of the cumulative distribution function of an interpolated area under a quality-of-life curve as summaries of the quality-of-life experience of a treatment group. A proposed estimator, although biased, offers an improvement over a Kaplan-Meier estimator that assumes incorrectly that the censoring is noninformative. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 10 TC 14 Z9 14 U1 0 U2 2 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 1993 VL 80 IS 3 BP 535 EP 542 DI 10.2307/2337175 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA MM819 UT WOS:A1993MM81900007 ER PT J AU NAM, JM AF NAM, JM TI BIAS-CORRECTED MAXIMUM-LIKELIHOOD ESTIMATOR OF A LOG COMMON ODDS RATIO SO BIOMETRIKA LA English DT Article DE BIAS-CORRECTED MAXIMUM LIKELIHOOD ESTIMATOR; COMMON ODDS RATIO; SPARSE DATA; STRATIFIED CASE-CONTROL STUDY ID NUISANCE PARAMETERS; MODELS; TABLES AB A bias-correction factor for the maximum likelihood estimator of the log common odds ratio for sparse data is derived, which is applicable when the design is balanced and/or when the number of strata is large. The corrected maximum likelihood estimator is practically unbiased and its mean squared error is smaller than that of the uncorrected maximum likelihood estimator. The correction factor for the maximum likelihood estimator approaches one as strata sizes increase. Examples demonstrate that the corrected maximum likelihood estimator and the exact conditional maximum likelihood estimator are essentially identical although the standard error of the former tends to be slightly smaller than that of the latter. It is also demonstrated that a simple version of the correction factor is a satisfactory approximation. The bias-corrected maximum likelihood estimator proposed in this paper is the extension of Breslow's (1981) and it can be useful particularly when the computational burden of the exact conditional method is excessive. RP NAM, JM (reprint author), NCI,BIOSTAT BRANCH,ROCKVILLE,MD 20892, USA. NR 19 TC 1 Z9 1 U1 0 U2 2 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 1993 VL 80 IS 3 BP 688 EP 694 DI 10.1093/biomet/80.3.688 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA MM819 UT WOS:A1993MM81900020 ER PT J AU POSNER, GH GUYTON, KZ KENSLER, TW BARSONY, J LIEBERMAN, ME REDDY, GS CLARK, JW WANKADIYA, KF TSERNG, KY AF POSNER, GH GUYTON, KZ KENSLER, TW BARSONY, J LIEBERMAN, ME REDDY, GS CLARK, JW WANKADIYA, KF TSERNG, KY TI 1-(HYDROXYALKYL)-25-HYDROXYVITAMIN-D3 ANALOGS OF CALCITRIOL .2. PRELIMINARY BIOLOGICAL EVALUATION SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID METABOLISM; 1,25-DIHYDROXYVITAMIN-D3; FIBROBLASTS; EXPRESSION; RECEPTOR; CELLS AB 1Alpha-hydroxymethyl-25-hydroxyvitamin D3 homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells, (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1beta-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1alpha-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV TOXICOL SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR ENVIRONM HLTH SCI,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. NIDDK,MINERAL METAB SECT,BETHESDA,MD 20892. BROWN UNIV,WOMEN & INFANTS HOSP,SCH MED,DEPT PEDIAT,PROVIDENCE,RI 02905. BROWN UNIV,ROGER WILLIAMS MED CTR,SCH MED,DEPT MED,PROVIDENCE,RI 02908. CASE WESTERN RESERVE UNIV,VET ADM MED CTR,MED RES SERV,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT NUTR & MED,CLEVELAND,OH 44106. RP POSNER, GH (reprint author), JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218, USA. RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X NR 11 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP PY 1993 VL 3 IS 9 BP 1835 EP 1840 DI 10.1016/S0960-894X(00)80115-8 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA MB522 UT WOS:A1993MB52200012 ER PT J AU GERSHFELD, NL MUDD, CP TAJIMA, K BERGER, RL AF GERSHFELD, NL MUDD, CP TAJIMA, K BERGER, RL TI CRITICAL-TEMPERATURE FOR UNILAMELLAR VESICLE FORMATION IN DIMYRISTOYLPHOSPHATIDYLCHOLINE DISPERSIONS FROM SPECIFIC-HEAT MEASUREMENTS SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOSPHOLIPID SURFACE BILAYERS; AIR-WATER-INTERFACE; INSTABILITY; MEMBRANES; STATE AB Using a heat conduction calorimeter with very high resolution (+/-0.00005 J/degrees-C.cm3), we have measured the specific heat Cp(L) between 25 and 35-degrees-C of dimyristoylphosphatidylcholine (DMPC) in aqueous dispersions. Previous studies of the temperature dependence of the chemical potential of DMPC in the Lalpha phase (lamellar, liquid crystalline) indicated that a dispersion consisting only of unilamellar vesicles forms spontaneously at a critical temperature T* of 29.0-degrees-C. Our present measurements show an anomaly in Cp(L) between 28.70 and 29.50-degrees-C: the curve for Cp(L) versus T first decreases and then exhibits an inflection point at 28.96-degrees-C before it flattens. This anomaly is attributed to the transformation from multilamellar dispersion to unilamellar vesicles at T* = 28.96-degrees-C. Two independent properties of the Cp(L) data also indicate T* is a critical point for the formation of unilamellar vesicles: (a) the time to reach equilibrium upon changing temperature increased dramatically between 28.7 and 28.96-degrees-C, increasing as (T* - T)-1; at T > T* the dramatic ''slowing-down'' phenomenon was not observed. This slowing-down near T* is a general characteristic of critical phenomena. (b) The free energy change for the multilamellar-unilamellar transformation was obtained from the Cp(L)-T data over this temperature interval and found to be 3.2 J/mol or 0.016 ergs/cm2 of bilayer, in agreement with other estimates of the interaction energy between neutral bilayers. We conclude with a discussion of the implications for membrane bilayer stability of these newly identified dynamic properties of the transformation. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP GERSHFELD, NL (reprint author), NIAMSD,PHYS BIOL LAB,BLDG 6,ROOM 139,BETHESDA,MD 20892, USA. NR 23 TC 23 Z9 23 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 SEP PY 1993 VL 65 IS 3 BP 1174 EP 1179 PG 6 WC Biophysics SC Biophysics GA LW934 UT WOS:A1993LW93400023 PM 8241397 ER PT J AU HENDLER, RW BOSE, SK SHRAGER, RI AF HENDLER, RW BOSE, SK SHRAGER, RI TI MULTIWAVELENGTH ANALYSIS OF THE KINETICS OF REDUCTION OF CYTOCHROME-AA(3) BY CYTOCHROME-C SO BIOPHYSICAL JOURNAL LA English DT Article ID BEEF-HEART ENZYME; PARACOCCUS-DENITRIFICANS; FERROCYTOCHROME-C; CARBON-MONOXIDE; OXIDASE; 2-SUBUNIT; SPECTRA; AA3 AB Some new approaches to the kinetic study of the reduction of cytochrome aa3 by cytochrome c are presented. The primary innovations are the use of a spectrometer which can acquire multiwavelength data as fast as every 10 mus, and the application of a variety of analytical methods which can utilize simultaneously all of the time-resolved spectral data. These techniques include singular value decomposition (SVD), deconvolutions based on pure Gaussian models for absorption peaks, deconvolutions based on isolated absorption spectra for the pure components, and simulations of SVD-deduced and actual experimental difference spectra. The reduction characteristics of the anaerobic resting enzyme can be distinguished from those of pulsed forms. In the former case, only two electrons can be bound by cytochrome aa3, whereas in the latter case complete reduction of the enzyme is achieved. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP HENDLER, RW (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 16 Z9 16 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1993 VL 65 IS 3 BP 1307 EP 1317 PG 11 WC Biophysics SC Biophysics GA LW934 UT WOS:A1993LW93400037 PM 8241410 ER PT J AU SAROFF, HA AF SAROFF, HA TI INDIVIDUAL-SITE BINDING DATA AND THE ENERGETICS OF PROTEIN-DNA INTERACTIONS SO BIOPOLYMERS LA English DT Article ID LAMBDA-PHAGE REPRESSOR; RESOLUTION; OPERATOR AB Individual-site isotherms for the binding of bacteriophage lambda repressor to the left and right lambda operators have been determined [D. F. Senear, M. Brenowitz, M. A. Shea, and G. K. Ackers (1986) Biochemistry, Vol. 25, pp. 7344-7354.] using the DNAse protection technique [footprinting; D. J. Galas and A. Schmitz (1978) Nucleic Acids Research, Vol. 5, pp. 3157-3170]. These extensive data have been interpreted with a quantitative model that emphasized cooperative interactions between adjacently bound ligands [occupied <-> occupied interactions; G. K. Ackers, A. D. Johnson, and M. A. Shea (1982) Proceedings of the National Academy of Science, USA, Vol. 79, pp. 1129-1133]. Overlooked in this model are the effects of cooperative interactions between a site containing a bound ligand and its neighboring unoccupied site (occupied <-> unoccupied interactions). This paper reinterprets the existing data with a model that considers occupied <-> unoccupied as well as occupied <-> occupied interactions. The results yield parameters that differ substantially from those already reported. A discussion on the advisability of ignoring occupied <-> unoccupied interactions is included. (C) 1993 John Wiley & Sons, Inc. RP SAROFF, HA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 227,BETHESDA,MD 20892, USA. NR 14 TC 5 Z9 5 U1 1 U2 1 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 SEP PY 1993 VL 33 IS 9 BP 1327 EP 1336 DI 10.1002/bip.360330903 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT692 UT WOS:A1993LT69200002 PM 8400030 ER PT J AU SAFAR, J ROLLER, PP RUBEN, GC GAJDUSEK, DC GIBBS, CJ AF SAFAR, J ROLLER, PP RUBEN, GC GAJDUSEK, DC GIBBS, CJ TI SECONDARY STRUCTURE OF PROTEINS ASSOCIATED IN THIN-FILMS SO BIOPOLYMERS LA English DT Article ID BETA-SHEETS; CIRCULAR-DICHROISM; IR SPECTROSCOPY; RIBONUCLEASE-A; SILK FIBROIN; CONFORMATION; OLIGOPEPTIDES; POLYPEPTIDES; SEQUENCES; ARTIFACTS AB The solid state secondary structure of myoglobin, RNase A, concanavalin A (Con A), poly(L-lysine), and two linear heterooligomeric peptides were examined by both far-uv CD spectroscopy1 and by ir spectroscopy. The proteins associated from water solution on glass and mica surfaces into noncrystalline, amorphous films, as judged by transmission electron microscopy of carbon-platinum replicas of surface and cross-fractured layer. The association into the solid state induced insignificant changes in the amide CD spectra of all alpha-helical myoglobin, decreased the molar ellipticity of the alpha/beta RNase A, and increased the molar ellipticity of all-beta Con A with no change in the positions of the bands' maxima. High-temperature exposure of the films induced permanent changes in the conformation of all proteins, resulting in less alpha-helix and more beta-sheet structure. The results suggest that the protein alpha-helices are less stable in films and that the secondary structure may rearrange into beta-sheets at high temperature. Two heterooligomeric peptides and poly(L-lysine), all in solution at neutral pH with ''random coil'' conformation, formed films with variable degrees of their secondary structure in beta-sheets or beta-turns. The result corresponded to the protein-derived Chou-Fasman amino acid propensities, and depended on both temperature and solvent used. The ir and CD spectra correlations of the peptides in the solid state indicate that the CD spectrum of a ''random'' structure in films differs from random coil in solution. Formic acid treatment transformed the secondary structure of the protein and peptide films into a stable alpha-helix or beta-sheet conformations. The results indicate that the proteins aggregate into a noncrystalline, glass-like state with preserved secondary structure. The solid state secondary structure may undergo further irreversible transformations induced by heat or solvent. (C) 1993 John Wiley & Sons, Inc. C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. DARTMOUTH COLL,DEPT BIOL SCI,HANOVER,NH 03755. 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 62 TC 42 Z9 43 U1 3 U2 15 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 SEP PY 1993 VL 33 IS 9 BP 1461 EP 1476 DI 10.1002/bip.360330915 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT692 UT WOS:A1993LT69200014 PM 8400035 ER PT J AU SUN, Y HEGAMYER, G COLBURN, NH AF SUN, Y HEGAMYER, G COLBURN, NH TI PCR-DIRECT SEQUENCING OF A GC-RICH REGION BY INCLUSION OF 10-PERCENT DMSO - APPLICATION TO MOUSE C-JUN SO BIOTECHNIQUES LA English DT Note ID GENE; DNA RP SUN, Y (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702, USA. NR 10 TC 34 Z9 37 U1 1 U2 6 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1993 VL 15 IS 3 BP 372 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LW417 UT WOS:A1993LW41700005 PM 8217142 ER PT J AU WEGHORST, CM BUZARD, GS AF WEGHORST, CM BUZARD, GS TI ENHANCED SINGLE-STRAND CONFORMATION POLYMORPHISM (SSCP) DETECTION OF POINT MUTATIONS UTILIZING METHYLMERCURY HYDROXIDE SO BIOTECHNIQUES LA English DT Note ID GEL-ELECTROPHORESIS; DNA C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS DEV PROGRAM,PROGRAM RESOURCES DYNCORP,FREDERICK,MD 21702. RP WEGHORST, CM (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 4 TC 8 Z9 8 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1993 VL 15 IS 3 BP 396 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LW417 UT WOS:A1993LW41700013 PM 8217149 ER PT J AU MYSLOBODSKY, MS AF MYSLOBODSKY, MS TI CENTRAL DETERMINANTS OF ATTENTION AND MOOD DISORDER IN TARDIVE-DYSKINESIA (TARDIVE DYSMENTIA) SO BRAIN AND COGNITION LA English DT Article ID CEREBRAL BLOOD-FLOW; CHRONIC-SCHIZOPHRENIA; LEFT-HEMISPHERE; HUMAN AUTONOMY; FRONTAL LOBES; BEHAVIOR; NEUROLEPTICS; TOMOGRAPHY; CORTEX; ABNORMALITIES C1 NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, BETHESDA, MD 20892 USA. RP MYSLOBODSKY, MS (reprint author), TEL AVIV UNIV, DEPT PSYCHOL, PSYCHOBIOL RES UNIT, IL-69978 TEL AVIV, ISRAEL. NR 79 TC 6 Z9 6 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD SEP PY 1993 VL 23 IS 1 BP 88 EP 101 DI 10.1006/brcg.1993.1047 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA LW416 UT WOS:A1993LW41600008 PM 8217124 ER PT J AU FRIDE, E MCINTYRE, T SKOLNICK, P ARORA, PK AF FRIDE, E MCINTYRE, T SKOLNICK, P ARORA, PK TI IMMUNOCOMPETENCE IN THE LONG-SLEEP AND SHORT-SLEEP MOUSE LINES - BASE-LINE VERSUS PRIMED RESPONSES SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article ID CHLORIDE CHANNEL COMPLEX; CYTOTOXIC T-LYMPHOCYTES; GENETIC-CONTROL; RECEPTOR; CELLS; MICE; DIAZEPAM; ALCOHOL; SUPPRESSION; SENSITIVITY C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NR 32 TC 3 Z9 3 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD SEP PY 1993 VL 7 IS 3 BP 231 EP 242 DI 10.1006/brbi.1993.1024 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA LW419 UT WOS:A1993LW41900004 PM 8219412 ER PT J AU ARONSON, BD BELLPEDERSEN, D BLOCK, GD BOS, NPA DUNLAP, JC ESKIN, A GARCEAU, NY GEUSZ, ME JOHNSON, KA KHALSA, SBS KOSTERVANHOFFEN, GC KOUMENIS, C LEE, TM LESAUTER, J LINDGREN, KM LIU, QY LOROS, JJ MICHEL, SH MIRMIRAN, M MOORE, RY RUBY, NF SILVER, R TUREK, FW ZATZ, M ZUCKER, I AF ARONSON, BD BELLPEDERSEN, D BLOCK, GD BOS, NPA DUNLAP, JC ESKIN, A GARCEAU, NY GEUSZ, ME JOHNSON, KA KHALSA, SBS KOSTERVANHOFFEN, GC KOUMENIS, C LEE, TM LESAUTER, J LINDGREN, KM LIU, QY LOROS, JJ MICHEL, SH MIRMIRAN, M MOORE, RY RUBY, NF SILVER, R TUREK, FW ZATZ, M ZUCKER, I TI CIRCADIAN-RHYTHMS SO BRAIN RESEARCH REVIEWS LA English DT Article DE SUPRACHIASMATIC NUCLEUS; RETINA; TRANSPLANT; PINEAL GLAND; MELATONIN; APLYSIA; NEUROSPORA; PACEMAKER ID RAT SUPRACHIASMATIC NUCLEUS; CHICK PINEAL CELLS; PHOTOENDOCRINE TRANSDUCTION; MELATONIN RHYTHM; CALCIUM INFLUX; VASOPRESSIN RELEASE; GLUCOSE-UTILIZATION; CELLULAR ANALYSIS; PROTEIN-SYNTHESIS; PACEMAKER SYSTEM AB Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation - its organization, mechanism and consequences - unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Etude du Systeme Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on 'Circadian Rhythms', Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 2A-17,BETHESDA,MD 20892. RI Koumenis, Constantinos/B-2002-2008; Mirmiran, Majid/A-2708-2010; Loros, Jennifer/B-6293-2014; Bell-Pedersen, Deborah/H-8012-2016; Dunlap, Jay/L-6232-2013; OI Bell-Pedersen, Deborah/0000-0002-1639-8215; Dunlap, Jay/0000-0003-1577-0457; Lee, Theresa/0000-0002-9508-6382 NR 89 TC 43 Z9 45 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD SEP-DEC PY 1993 VL 18 IS 3 BP 315 EP 333 DI 10.1016/0165-0173(93)90015-R PG 19 WC Neurosciences SC Neurosciences & Neurology GA LR291 UT WOS:A1993LR29100003 PM 8401597 ER PT J AU STURGEON, SR BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD AF STURGEON, SR BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD TI PAST AND PRESENT PHYSICAL-ACTIVITY AND ENDOMETRIAL CANCER RISK SO BRITISH JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER; EPIDEMIOLOGY; HORMONES AB We examined the relation between physical activity and endometrial cancer using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. Estimates of recreational (i.e. active sport, walks and hikes) and nonrecreational activity (i.e. house cleaning, climbing stairs and walking or standing on the job) were obtained using interview information. After adjustment for age, study area, education, parity, years of use of oral contraceptives, years of use of menopausal oestrogens and cigarette smoking, recent recreational inactivity was associated with increased risk (RR = 1.9 for lowest vs highest tertile). Similarly, recent nonrecreational inactivity was associated with increased risk (RR = 2.2 for lowest vs highest tertile). Further adjustment for body mass and nonrecreational activity attenuated the association between risk and recent recreational inactivity (RR = 1.2; 95% CL = 0.7-2.0) but adjustment for body mass and recreational activity did not alter the association between risk and recent nonrecreational inactivity (RR = 2.0; 95% CL = 1.2-3.1). To evaluate the relation between risk and sustained inactivity, we simultaneously examined activity levels at three periods (i.e. age 20-29, age 30-39 and recently) in women age 50 and older. After adjustment for potential confounders and body mass, risk was elevated among women who were always recreationally inactive (RR = 1.5 for always active vs always inactive) and among women who were always nonrecreationally inactive (RR = 1.6 for always active vs always inactive). This study suggests that physically inactive women may be at increased risk of endometrial cancer because they are more likely to be overweight or obese. Our data also suggest that inactivity per se may be associated with an increased risk of endometrial cancer. However, we cannot rule out the possibility that our results, particularly those for nonrecreational activity, reflect unmeasured confounding factors. Future studies should attempt to obtain more detailed assessments of physical activity, including the intensity with which an individual engaged in an activity and the actual time involved in exertion. C1 RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. UNIV MINNESOTA,HLTH SCI CTR,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV CALIF IRVINE,IRVINE MED CTR,DEPT OBSTET & GYNECOL,ORANGE,CA 92668. RP STURGEON, SR (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 16 TC 57 Z9 58 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1993 VL 68 IS 3 BP 584 EP 589 DI 10.1038/bjc.1993.390 PG 6 WC Oncology SC Oncology GA LU741 UT WOS:A1993LU74100024 PM 8353048 ER PT J AU MURPHY, DGM MURPHY, DM ABBAS, M PALAZIDOU, E BINNIE, C ARENDT, J COSTA, DC CHECKLEY, SA AF MURPHY, DGM MURPHY, DM ABBAS, M PALAZIDOU, E BINNIE, C ARENDT, J COSTA, DC CHECKLEY, SA TI SEASONAL AFFECTIVE-DISORDER - RESPONSE TO LIGHT AS MEASURED BY ELECTROENCEPHALOGRAM, MELATONIN SUPPRESSION, AND CEREBRAL BLOOD-FLOW SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article AB This study was designed to test the hypothesis that patients with SAD have significantly different physiological responses to light than healthy age- and sex-matched controls. We studied retinal contrast sensitivity, visual evoked EEG responses, and melatonin suppression by, and cerebral blood flow response to, full-spectrum artificial daylight. There was no significant difference between 10 patients and 11 controls in retinal contrast sensitivity, or amplitude or latency of N2, P2, P100 or P300 on EEG. We compared melatonin suppression in 12 SAD patients and 12 controls. During exposure to 500 lux and 1500 lux artificial daylight both the SAD patients and controls had a significant melatonin percentage suppression; however, the percentage suppression did not differ significantly between the SAD patients and the controls. In addition, we carried out a small pilot study into the effect of light on cerebral blood flow in four SAD patients and four controls. Before exposure to 1500 lux artificial daylight there was no significant difference between patients and controls in global, regional or cerebral hemispheric blood flow. After light exposure the SAD patients and controls had a significantly different percentage change in cerebral blood flow. We suggest that patients with SAD do not have significantly physiological responses to light than controls, except perhaps in cerebral blood flow. Furthermore, mechanisms other than supersensitivity of melatonin suppression must explain both the pathophysiology of the disorder and its response to treatment with light. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 414,5000 ROCKVILLE PK,BETHESDA,MD 20892. INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. ST GEORGE HOSP,SCH MED,LONDON,ENGLAND. CTY HOSP LINCOLN,PETER HODGKINSON CTR,LINCOLN,ENGLAND. ROYAL LONDON HOSP,LONDON,ENGLAND. MAUDSLEY HOSP & INST PSYCHIAT,LONDON SE5 8AZ,ENGLAND. CHARING CROSS HOSP & MED SCH,LONDON,ENGLAND. BETHLEM ROYAL & MAUDSLEY HOSP,LONDON,ENGLAND. UNIV SURREY,DEPT BIOCHEM,GUILDFORD GU2 5XH,SURREY,ENGLAND. NR 0 TC 28 Z9 28 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1993 VL 163 BP 327 EP 331 DI 10.1192/bjp.163.3.327 PG 5 WC Psychiatry SC Psychiatry GA LY464 UT WOS:A1993LY46400007 PM 8401961 ER PT J AU CHECKLEY, SA MURPHY, DGM ABBAS, M MARKS, M WINTON, F PALAZIDOU, E MURPHY, DM FRANEY, C ARENDT, J AF CHECKLEY, SA MURPHY, DGM ABBAS, M MARKS, M WINTON, F PALAZIDOU, E MURPHY, DM FRANEY, C ARENDT, J TI MELATONIN RHYTHMS IN SEASONAL AFFECTIVE-DISORDER SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL BLOOD-FLOW; LIGHT TREATMENT; BRIGHT LIGHT; PHASE-SHIFTS; DIM LIGHT; ANTIDEPRESSANT; SUPPRESSION; PHOTOTHERAPY; DEPRESSION; THERAPY AB We examined 24-hour melatonin rhythms from 20 patients with seasonal affective disorder (SAD) and 20 healthy volunteers. Patients and controls were individually matched for age, sex, and month of study. Plasma samples were taken at hourly intervals, and were assayed for melatonin by radio-immunoassay. The 24-hourly melatonin estimations for each individual were fitted to a cosine curve, and the significance of the curve fits was calculated. Two analyses were performed. In analysis 1 the following were calculated: (a) cosine fit, (b) significance of fits, (c) mean amplitude and acrophase (peak) and (d) mean melatonin levels. The curve fits were highly significant for all but three subjects (two patients, one control), but there were no significant differences in any measure between the two groups. In analysis 2 the comparisons were repeated and restricted to the 18 patients and 19 controls in whom there was a statistically significant melatonin rhythm. Again there were no significant differences between groups. These results suggest that the circadian rhythm of melatonin is not abnormal in SAD, and that the therapeutic effect of light in SAD is not mediated by phase shifts in melatonin secretion. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. CHARING CROSS HOSP & MED SCH,LONDON,ENGLAND. INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. CTY HOSP LINCOLN,PETER HODGKINSON CTR,LINCOLN,ENGLAND. ROYAL LONDON HOSP,LONDON,ENGLAND. ST GEORGE HOSP,SCH MED,LONDON,ENGLAND. UNIV SURREY,DEPT BIOCHEM,GUILDFORD GU2 5XH,SURREY,ENGLAND. MAUDSLEY HOSP & INST PSYCHIAT,LONDON SE5 8AZ,ENGLAND. BETHLEM ROYAL & MAUDSLEY HOSP,LONDON,ENGLAND. NR 54 TC 49 Z9 49 U1 1 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1993 VL 163 BP 332 EP 337 DI 10.1192/bjp.163.3.332 PG 6 WC Psychiatry SC Psychiatry GA LY464 UT WOS:A1993LY46400008 PM 8401962 ER PT J AU TOKUNAGA, M LAND, CE AOKI, Y YAMAMOTO, T ASANO, M SATO, E TOKUOKA, S SAKAMOTO, G PAGE, DL AF TOKUNAGA, M LAND, CE AOKI, Y YAMAMOTO, T ASANO, M SATO, E TOKUOKA, S SAKAMOTO, G PAGE, DL TI PROLIFERATIVE AND NONPROLIFERATIVE BREAST DISEASE IN ATOMIC-BOMB SURVIVORS - RESULTS OF A HISTOPATHOLOGIC REVIEW OF AUTOPSY BREAST-TISSUE SO CANCER LA English DT Article DE BREAST DISEASE; PROLIFERATIVE BREAST DISEASE; PATHOLOGY; IONIZING RADIATION; ATOMIC BOMB SURVIVORS; ATOMIC BOMB; AUTOPSY ID FLUOROSCOPIC EXAMINATIONS; FIBROCYSTIC DISEASE; FEMALE BREAST; FOLLOW-UP; X-RAYS; CANCER; WOMEN; EPIDEMIOLOGY; HIROSHIMA; NAGASAKI AB Background. The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. Methods. Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose, Results. Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. Conclusions. It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers. C1 JAPANESE FDN CANC RES,INST CANC,DEPT PATHOL,TOKYO 170,JAPAN. VANDERBILT UNIV,MED CTR,DEPT PATHOL,NASHVILLE,TN 37240. HIROSHIMA PREFECTURAL MED ASSOC,TUMOR REGISTRY,HIROSHIMA,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA,JAPAN. KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. KAGOSHIMA UNIV,FAC MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. YOSHIDA GEN HOSP,HIROSHIMA,JAPAN. NATL HOSP,MED CTR,TOKYO,JAPAN. NR 41 TC 14 Z9 15 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1993 VL 72 IS 5 BP 1657 EP 1665 DI 10.1002/1097-0142(19930901)72:5<1657::AID-CNCR2820720527>3.0.CO;2-N PG 9 WC Oncology SC Oncology GA LT807 UT WOS:A1993LT80700026 PM 8348497 ER PT J AU JABLON, S BOICE, JD AF JABLON, S BOICE, JD TI MORTALITY AMONG WORKERS AT A NUCLEAR-POWER-PLANT IN THE UNITED-STATES SO CANCER CAUSES & CONTROL LA English DT Article DE CANCER; EPIDEMIOLOGY; FOLLOW-UP; MORTALITY; NUCLEAR POWER; OCCUPATIONAL RADIATION EXPOSURE; UNITED-STATES AB A second follow-up of 9,000 workers at the Calvert Cliffs Nuclear Power Plant (MD, USA) identified 346 deaths in the years 1969-88, 101 of which were attributed to malignant neoplasms.The original study had the primary purpose of assessing the feasibility of studies of workers based upon individual plant and Nuclear Regulatory Commission records. The average, cumulative, occupational dose through 1984 was low, only 21 mSv, but ranged up to 470 mSv, with 12 percent of the workers receiving more than 50 mSv. Mortality from most causes of death was low and there was a deficit of deaths from diseases of the circulatory system. Ionizing radiation exposures were not related to the probability of death from neoplasms generally or from any specific form of cancer. There were only two deaths from leukemia, whereas four were expected at population death rates. Larger numbers of workers, followed for longer periods of time, are needed to determine the mortality risk to workers in the nuclear power industry. The difficulties in obtaining dose information for transient workers were so great, and so time consuming, as to make questionable the practicability of studying the workers at a large number of power plants in this way. RP JABLON, S (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N 408,BETHESDA,MD 20892, USA. NR 0 TC 10 Z9 10 U1 0 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 SEP PY 1993 VL 4 IS 5 BP 427 EP 430 DI 10.1007/BF00050861 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA MA383 UT WOS:A1993MA38300004 PM 8218874 ER PT J AU WEI, Z MCLAUGHLIN, JK GRIDLEY, G BJELKE, E SCHUMAN, LM SILVERMAN, DT WACHOLDER, S COCHIEN, HT BLOT, WJ FRAUMENI, JF AF WEI, Z MCLAUGHLIN, JK GRIDLEY, G BJELKE, E SCHUMAN, LM SILVERMAN, DT WACHOLDER, S COCHIEN, HT BLOT, WJ FRAUMENI, JF TI A COHORT STUDY OF SMOKING, ALCOHOL-CONSUMPTION, AND DIETARY FACTORS FOR PANCREATIC-CANCER (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE ALCOHOL DRINKING; COFFEE; COHORT STUDY; DIET; MORTALITY; PANCREATIC NEOPLASM; TOBACCO; UNITED-STATES; WHITE MALES AB Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 1993 VL 4 IS 5 BP 477 EP 482 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA MA383 UT WOS:A1993MA38300010 ER PT J AU HERMAN, EH FERRANS, VJ AF HERMAN, EH FERRANS, VJ TI TIMING OF TREATMENT WITH ICRF-187 AND ITS EFFECT ON CHRONIC DOXORUBICIN CARDIOTOXICITY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article ID SYRIAN GOLDEN-HAMSTERS; (+/-)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE ICRF-187; ADRIAMYCIN CARDIOTOXICITY; DAUNORUBICIN; REDUCTION; PHARMACOKINETICS; PRETREATMENT; DAUNOMYCIN; TOXICITY; RATS AB Studies were conducted to evaluate whether the timing of administration of ICRF-187 [(+)-1,2-bis(3,5 dioxopiperazinyl-1-yl)propane] would influence the degree of cardioprotection provided by this agent against the development of doxorubicin-induced chronic cardiomyopathy. Beagle dogs (8.5-14 kg) received either doxorubicin alone (1.75 mg/kg, i. v., n = 8), doxorubicin (1.75 mg/kg) simultaneously with ICRF-187 (35 mg/kg, i. v., n = 8), or doxorubicin (1.75 mg/kg) followed 2 h later by ICRF-187 (35 mg/kg, n = 8). Control animals received ICRF-187 (35 mg/kg, n = 4) or saline (n = 4). All animals received a course of seven treatments, each given 3 weeks apart, and were killed 3 weeks after the last treatment. Semiquantitative grading of histologic sections of myocardium showed that as compared with animals treated with doxorubicin alone, the incidence and the severity of the doxorubicin-induced myocardial lesions were reduced in the two groups of animals given doxorubicin plus ICRF-187. However, protection was significantly better in dogs receiving ICRF-187 and doxorubicin simultaneously than in those given ICRF-187 2 h after doxorubicin. These observations were interpreted as indicating that the timing of administration of ICRF-187 with respect to that of doxorubicin is an important factor in determining the degree of cardioprotection and that there is a ''time window'' in which ICRF-187 exerts optimal effects. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP HERMAN, EH (reprint author), US FDA,DIV RES & TESTING,MOD 1 FACIL,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 29 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1993 VL 32 IS 6 BP 445 EP 449 DI 10.1007/BF00685888 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LR870 UT WOS:A1993LR87000006 PM 8258192 ER PT J AU FELKER, GM FRIEDMAN, HS DOLAN, ME MOSCHEL, RC SCHOLD, C AF FELKER, GM FRIEDMAN, HS DOLAN, ME MOSCHEL, RC SCHOLD, C TI TREATMENT OF SUBCUTANEOUS AND INTRACRANIAL BRAIN-TUMOR XENOGRAFTS WITH O-6-BENZYLGUANINE AND 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; CROSS-LINK FORMATION; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; HUMAN GLIOMA; CYTO-TOXICITY; ATHYMIC MICE; HUMAN-CELLS; SENSITIVITY; TISSUES AB O6-Alkylguanine-DNA alkyltransferase (AT) is a cellular protein that protects cells from the cytotoxic effects of nitrosoureas by repairing alkyl lesions at the O6 position of guanine. We have studied the ability of O6-benzylguanine to deplete AT activity in brain tumor xenografts and thereby increase the sensitivity of these tumors to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In toxicity studies, pretreatment of athymic mice with O6-benzylguanine increased the toxicity of BCNU significantly. After i. p. injection of O6-benzylguanine into athymic mice carrying subcutaneous (s.c.) D341MED, a human medulloblastoma xenograft with a high AT activity, the AT activity of the tumors became undetectable within 1 h and remained depleted until 36 h. In s. c. xenografts to D341MED, treatment with O6-benzylguanine followed 1 h later by BCNU produced a significantly greater growth delay (14.8 days) than was seen with BCNU alone (2.3 days). A lower pretreatment dose of O6-benzylguanine produced a significantly smaller therapeutic effect. Delaying the administration of BCNU until 36 h after O6-benzylguanine resulted in a growth delay (1.2 days) that was not significantly different from that produced by the control or BCNU alone. In athymic mice with intracranial (i.c.) xenografts of D341MED; pretreatment with O6-benzylguanine followed 1 h later by BCNU produced a significantly increased survival as compared with that of the control, BCNU alone, O6-benzylguanine alone, and O6-benzylguanine followed 36 h later by BCNU. In experiments with s.c. xenografts of D245MG, a human glioma xenograft with undetectable AT activity, pretreatment with O6-benzylguanine 1 h prior to BCNU produced a significantly greater effect than was seen with BCNU treatment alone. The combination regimen, however, was not as effective as an equitoxic dose of BCNU alone. These studies suggest that O6-benzylguanine may be a useful adjuvant to nitrosourea therapy in human malignancies that exhibit a range of AT activities and that dose and timing are important variables in achieving therapeutic success. These data also indicate that therapeutic potentiation of BCNU by O6-benzylguanine can be achieved in i. c. tumors. As a result, this approach may be useful in the treatment of neoplasms of the central nervous system. C1 DUKE UNIV,SCH MED,EDITORIAL OFF,DURHAM,NC 27706. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,DEPT NEUROL,DALLAS,TX 75235. FU NCI NIH HHS [CA-47228]; NINDS NIH HHS [NS-20581, NS-30245] NR 30 TC 79 Z9 80 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1993 VL 32 IS 6 BP 471 EP 476 DI 10.1007/BF00685892 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LR870 UT WOS:A1993LR87000010 PM 8258196 ER PT J AU OLSEN, JH WALLIN, H BOICE, JD RASK, K SCHULGEN, G FRAUMENI, JF AF OLSEN, JH WALLIN, H BOICE, JD RASK, K SCHULGEN, G FRAUMENI, JF TI PHENOBARBITAL, DRUG-METABOLISM, AND HUMAN CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ANTICONVULSANT DRUGS; URINARY-BLADDER; FOLLOW-UP; LUNG; RATS; CARCINOGENESIS; DNA; 4-AMINOBIPHENYL; INDUCTION; DOSIMETRY AB To investigate the possible influence of anticonvulsant treatment on cancer risk, a nested case-control study of 104 lung cancers, 18 bladder cancers, and 322 cancer-free controls was conducted. The background for the study was previous observations among 8004 epileptics in Denmark with a significantly high risk for lung cancer and a significantly low risk for bladder cancer. Cigarette smoking appears to explain the lung cancer excess but not the low risk for bladder cancer, another tobacco-related disease. Information was abstracted on 94 and 95% of the cases and controls, respectively. Lung cancer was not associated with any anticonvulsant drug, but bladder cancer was inversely related to use of phenobarbital (PB). The apparent protective effect of PB was further evaluated in a study of rats given 4-aminobiphenyl (ABP), a bladder carcinogen. The levels of 4-aminobiphenyl adducts in hemoglobin and in bladder and liver DNA were significantly lower in rats given PB prior to 4-aminobiphenyl, compared to controls. These studies suggest that PB may induce drug-metabolizing enzymes of the liver that deactivate bladder carcinogens found in cigarette smoke and provide clues to the role of activation and detoxification of carcinogens in humans. C1 FILADELFIA EPILEPSY CTR,DK-4293 DIANALUND,DENMARK. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. DANISH CANC SOC,FIBIGER INST,DK-2100 COPENHAGEN,DENMARK. UNIV FREIBURG,INST MED BIOMETRY & INFORMAT,W-7800 FREIBURG,GERMANY. RP OLSEN, JH (reprint author), DANISH CANC SOC,DANISH CANC REGISTRY,ROSENVAENGETS HOVEDVEJ 35,BOX 839,DK-2100 COPENHAGEN,DENMARK. RI rask, kimberly/M-8001-2016; Wallin, Hakan/I-6459-2012 OI Wallin, Hakan/0000-0001-7716-0166 NR 24 TC 33 Z9 33 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1993 VL 2 IS 5 BP 449 EP 452 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LX261 UT WOS:A1993LX26100008 PM 8220089 ER PT J AU SURUDA, A SCHULTE, P BOENIGER, M HAYES, RB LIVINGSTON, GK STEENLAND, K STEWART, P HERRICK, R DOUTHIT, D FINGERHUT, MA AF SURUDA, A SCHULTE, P BOENIGER, M HAYES, RB LIVINGSTON, GK STEENLAND, K STEWART, P HERRICK, R DOUTHIT, D FINGERHUT, MA TI CYTOGENETIC EFFECTS OF FORMALDEHYDE EXPOSURE IN STUDENTS OF MORTUARY SCIENCE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ETHYLENE-OXIDE; CHROMOSOME-ABERRATIONS; BIOLOGIC MARKERS; OCCUPATIONAL EXPOSURES; EXFOLIATED CELLS; NASAL CAVITY; ORAL-MUCOSA; WORKERS; CANCER; LYMPHOCYTES AB The effect of low-level exposure to formaldehyde on oral, nasal, and lymphocyte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose-response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in,blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. UNIV CINCINNATI,SCH MED,DEPT ENVIRONM HLTH SCI,CINCINNATI,OH 45221. NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDIES,CINCINNATI,OH 45226. CINCINNATI COLL MORTUARY SCI,CINCINNATI,OH. NR 72 TC 91 Z9 95 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1993 VL 2 IS 5 BP 453 EP 460 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LX261 UT WOS:A1993LX26100009 PM 8220090 ER PT J AU SINHA, R PATTERSON, BH MANGELS, AR LEVANDER, OA GIBSON, T TAYLOR, PR BLOCK, G AF SINHA, R PATTERSON, BH MANGELS, AR LEVANDER, OA GIBSON, T TAYLOR, PR BLOCK, G TI DETERMINANTS OF PLASMA VITAMIN-E IN HEALTHY-MALES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALPHA-TOCOPHEROL; GAMMA-TOCOPHEROL; BETA-CAROTENE; INTERVIEW SURVEY; A-I; LIPOPROTEINS; SERUM; QUESTIONNAIRE; TRANSPORT; DIETARY AB Vitamin E or tocopherol, a known antioxidant, may play a role in the etiology of chronic diseases such as cancer and heart disease. This study examined both ''internal'' (lipids, lipoproteins, and apoproteins) and ''external'' (dietary components, physical activity, and body mass index) factors which may influence plasma alpha-tocopherol and gamma-tocopherol levels. Analyses were done using dietary questionnaires and plasma obtained from 65 nonsmoking male volunteers aged 30-59 years. Forty-six men did not take any supplements while 19 took supplements containing vitamin E. A positive correlation (r = 0.32; P < 0.01) between vitamin E intake and alpha-tocopherol status [(ratio of plasma alpha- or gamma-tocopherol/(total triglycerides + total cholesterol)] and a negative correlation (r = -0.33; P < 0.007) between intake and gamma-tocopherol status were observed. The main internal factors, or determinants, for plasma alpha-tocopherol for nonsupplement users were plasma triglycerides and apoproteins, apoA1 and apoB, but neither lipids nor apoproteins appeared to affect tocopherol levels in supplement users. External determinants of alpha-tocopherol status in nonsupplement users were vitamin E intake, total fat intake, and body mass index, while in supplement users only vitamin E intake was important. Both vitamin E intake and alcohol intake appeared to affect plasma gamma-tocopherol status in a negative manner. C1 USDA, BELTSVILLE HUMAN NUTR RES CTR, BELTSVILLE, MD 20705 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD 20906 USA. UNIV CALIF BERKELEY, DEPT PUBL HLTH, BERKELEY, CA 94720 USA. RP NCI, DIV CANC PREVENT & CONTROL, EPN RM 443, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Block, Gladys/E-3304-2010; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 47 TC 51 Z9 51 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1993 VL 2 IS 5 BP 473 EP 479 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LX261 UT WOS:A1993LX26100012 PM 8220093 ER PT J AU SHIELDS, PG CAPORASO, NE FALK, RT SUGIMURA, H TRIVERS, GE TRUMP, BF HOOVER, RN WESTON, A HARRIS, CC AF SHIELDS, PG CAPORASO, NE FALK, RT SUGIMURA, H TRIVERS, GE TRUMP, BF HOOVER, RN WESTON, A HARRIS, CC TI LUNG-CANCER, RACE, AND A CYP1A1 GENETIC-POLYMORPHISM SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYTOCHROME-P450IA1 GENE; SUSCEPTIBILITY; LOCUS; BENZO(ALPHA)PYRENE; BENZOPYRENE; METABOLITES; LYMPHOCYTES; ASSOCIATION; CARCINOGEN; POPULATION AB The assessment of human cancer risk using molecular epidemiological techniques involves determining the relative contributions of inherited and acquired genetic predispositions, in the context of environmental exposures. Recently described genetic polymorphisms for CYP1A1, a gene involved in the metabolic activation of polycyclic aromatic hydrocarbons, have been associated with lung cancer risk in a Japanese population. We report herein findings from a United States case-control study of lung cancer (56 cases; 48 controls). The polymerase chain reaction followed by an Msp1 restriction enzyme digestion was used to analyze constitutive DNA but no association between the restriction fragment length polymorphism and lung cancer risk was found (odds ratio, 0.7; 95% confidence interval, = 0.3-1.6). Analysis of genotype by cumulative smoking status did not reveal an elevated risk among lesser or greater smokers. The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7). When stratified by race, however, no association between case status and the polymorphism was observed, but the small number of study subjects within each racial group limited the statistical power. Larger studies are required to evaluate the risk of the CYP1A1 Msp1 polymorphism in African Americans. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT & EPIDEMIOL PROGRAM,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. RI Shields, Peter/I-1644-2012 NR 33 TC 107 Z9 111 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1993 VL 2 IS 5 BP 481 EP 485 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LX261 UT WOS:A1993LX26100013 PM 8220094 ER PT J AU DIWAN, BA ANDERSON, LM REHM, S RICE, JM AF DIWAN, BA ANDERSON, LM REHM, S RICE, JM TI TRANSPLACENTAL CARCINOGENICITY OF CISPLATIN - INITIATION OF SKIN TUMORS AND INDUCTION OF OTHER PRENEOPLASTIC AND NEOPLASTIC LESIONS IN SENCAR MICE SO CANCER RESEARCH LA English DT Note ID CIS-DIAMMINEDICHLOROPLATINUM; MOUSE; RATS; EMBRYOTOXICITY; CHEMOTHERAPY; CARCINOMA; PREGNANCY; CDDP AB cis-Dichlorodiammineplatinum (cis-DDP), an anticancer agent sometimes used in pregnant women for the treatment of malignant ovarian and uterine tumors, was tested for transplacental carcinogenic and/or tumor-initiating effects in SENCAR mice. Pregnant mice were given a single i.p. injection of either cis-DDP (7.5 mg/kg body weight) in 2.5% NaCl or the same weight-adjusted volume of NaCl (5 ml/kg body weight) on day 17 of gestation. Offspring were delivered and raised by their natural mothers until weaning at 3 weeks of age. Starting at week 4, offspring in experimental groups received topical applications of 2 mug 12-O-teradecanoylphorbol-13-acetate (TPA) in acetone twice a week for 20 weeks while those in control groups received only acetone (0.2 ml/application) for the same duration. The experiment was terminated at 25 weeks of age. A high incidence (18 of 37; 48.7%) of papillomas was observed in (offspring exposed transplacentally to cis-DDP and postnatally to TPA, while only 10% (4 of 40) of offspring exposed to TPA alone developed such tumors (P < 0.0002). Although no skin tumors were observed without TPA promotion, transplacental administration of cis-DDP resulted in development of thymic lymphomas, lung tumors, and proliferative kidney lesions in offspring. These results provide the first evidence that cis-DDP can initiate and/or induce preneoplastic and neoplastic lesions in multiple tissues transplacentally. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP DIWAN, BA (reprint author), NCI,FCRDC,PRI DYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 20 TC 24 Z9 24 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1993 VL 53 IS 17 BP 3874 EP 3876 PG 3 WC Oncology SC Oncology GA LU579 UT WOS:A1993LU57900007 PM 8358711 ER PT J AU BORDEN, EC LOTAN, R LEVENS, D YOUNG, CW AF BORDEN, EC LOTAN, R LEVENS, D YOUNG, CW TI DIFFERENTIATION THERAPY OF CANCER - LABORATORY AND CLINICAL INVESTIGATIONS SO CANCER RESEARCH LA English DT Editorial Material ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; MURINE ERYTHROLEUKEMIA-CELLS; POLYMERASE CHAIN-REACTION; DOWN-REGULATION; MESSENGER-RNA; GROWTH-FACTOR; RAR-ALPHA; C-MYC; EXPRESSION C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. NCI,PATHOL LAB,GENE REGULAT SECT,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. RP BORDEN, EC (reprint author), MED COLL WISCONSIN,CTR CANC,MILWAUKEE,WI 53226, USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU NCI NIH HHS [1R13CA57162-01] NR 52 TC 30 Z9 35 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 SEP 1 PY 1993 VL 53 IS 17 BP 4109 EP 4115 PG 7 WC Oncology SC Oncology GA LU579 UT WOS:A1993LU57900048 PM 8358740 ER PT J AU IIZASA, T MOMIKI, S BAUER, B CAAMANO, J METCALF, R LECHNER, J HARRIS, CC KLEINSZANTO, AJP AF IIZASA, T MOMIKI, S BAUER, B CAAMANO, J METCALF, R LECHNER, J HARRIS, CC KLEINSZANTO, AJP TI INVASIVE TUMORS DERIVED FROM XENOTRANSPLANTED, IMMORTALIZED HUMAN-CELLS AFTER IN-VIVO EXPOSURE TO CHEMICAL CARCINOGENS SO CARCINOGENESIS LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; TRANSFORMING GROWTH-FACTOR; NEOPLASTIC TRANSFORMATION; TOBACCO CARCINOGENESIS; DIFFERENTIATION; HYDROCARBONS; GENES; LINES; SERUM; BETA AB Several chemicals that are found in cigarette smoke or diesel oil engine exhausts, such as benzo[a]pyrene (B[a]P) and 1,6-dinitropyrene (DNP) are carcinogenic in experimental animal models. In the present study, we have exposed in vivo the xenotransplanted immortalized human bronchial epithelial cell tine BEAS-2B to the ultimate carcinogen of B[a]P, benzo[a]pyrene diolepoxide (BPDE), to DNP or to the benzo[e]pyrene, a less active compound that has tumor-promoting abilities in mouse skin carcinogenesis bioassays. All three compounds were administered using slow-release beeswax pellets. After a 6 month exposure, BPDE produced two tumors in seven transplants, four tumors were seen in 10 transplants treated with DNP and one tumor was observed in five tracheal grafts exposed to B[a]P. All the neoplasms were well-differentiated invasive adenocarcinomas. Tracheal transplants exposed to beeswax without carcinogen did not show any evidence of neoplastic growth, and their luminal surfaces were lined by a single or double layer of cuboidal cells. All lines derived from the adenocarcinomas showed increased in vitro resistance to serum-induced terminal differentiation, gelatinolytic activity, s.c. tumorigenicity and invasive growth in an in vivo assay. When these cell lines were compared with previously described tumor cell lines derived from xenotransplants exposed to cigarette smoke condensate, it became clear that the latter exhibited a more aggressive invasive behavior. Nevertheless treatment with the three chemicals gave rise to tumor cell lines that exhibited a similar invasive behavior in vivo, and were able to penetrate early into the wall of the tracheal transplants in which they were seeded. These data indicate that this system based on xenotransplanted bronchial epithelial cells is a very relevant model to identify human carcinogens and to study mechanisms of bronchogenic cancer pathogenesis. C1 FOX CHASE CANC CTR,DEPT PATHOL,PHILADELPHIA,PA 19111. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Klein-Szanto, Andres/E-6218-2010; Caamano, Jorge/I-6778-2012 OI Caamano, Jorge/0000-0003-3530-7056 FU NCI NIH HHS [CA-06927, CA-44981]; NCRR NIH HHS [RR 05895] NR 30 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1993 VL 14 IS 9 BP 1789 EP 1794 DI 10.1093/carcin/14.9.1789 PG 6 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400011 PM 8403201 ER PT J AU LU, LJW ANDERSON, LM JONES, AB MOSKAL, TJ SALAZAR, JJ HOKANSON, JA RICE, JM AF LU, LJW ANDERSON, LM JONES, AB MOSKAL, TJ SALAZAR, JJ HOKANSON, JA RICE, JM TI PERSISTENCE, GESTATION STAGE-DEPENDENT FORMATION AND INTERRELATIONSHIP OF BENZO[A]PYRENE-INDUCED DNA-ADDUCTS IN MOTHERS, PLACENTAE AND FETUSES OF ERYTHROCEBUS-PATAS MONKEYS SO CARCINOGENESIS LA English DT Article ID HYDROCARBON HYDROXYLASE-ACTIVITY; DIOL-EPOXIDE; P-32-POSTLABELING TEST; METABOLIC-ACTIVATION; POSTNATAL TREATMENT; MOUSE-TISSUES; LUNG-CANCER; AH LOCUS; MICE; FETAL AB Since DNA adducts have been detected in the placentae of pregnant women who smoke cigarettes, the importance of these adducts as biomarkers of fetal exposure and risk has been evaluated using a non-human primate as a model. Pregnant Erythrocebus patas monkeys on days 50, 100 or 150 of gestation (term = 160 +/- 5 days) were treated once with 5-50 mg/kg benzo[a]pyrene (B[a]P), p.o. Fetuses were removed by Cesarean section 1 - 50 days after treatment and analyzed for DNA adducts by the nuclease P1 version of the P-32-postlabeling method. B[a]P induced high levels of DNA adducts in all fetal organs, placentae and maternal livers in all three trimesters of gestation. DNA adduct levels were higher in mid-gestation compared to early and late gestation. The major adduct detected was 10beta-(deoxyguanosin)-N2-yl-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydro-B[a]P. The adduct levels in fetal tissues increased with B[a]P dose, but at a much lower rate than in placentae or maternal livers. Preference in binding to DNA of various fetal organs was more apparent in early gestation compared to late gestation and at lower doses compared to higher doses. During early gestation and at low doses, B[a]P produced a similar level of DNA adducts in fetal lung, fetal liver, maternal liver and placenta. Individual fetal organ adduct levels correlated significantly with placental adduct levels, indicating placental and/or maternal contribution to genotoxic injuries in fetuses. However, the slopes of linear regression lines of correlation analyses varied among organs and among gestation stages at treatment, indicating fetal contribution to its own genotoxic injuries. DNA adduct levels in fetal skin were the lowest of all fetal organs tested and less affected by gestational stages at time of treatment. In contrast, DNA adduct levels in fetal liver exhibited distinct gestation stage specificity with higher adduct levels attained during mid-gestation compared to other stages of gestation. Adduct levels decreased at a much faster rate during the first 10-15 days compared to 15-50 days after B[a]P treatment. However, 10% of DNA adducts persisted 50 days after treatment in all organs studied. Together, the results suggest that placental adduction accurately indicates fetal exposure. Toxicokinetics of B[a]P and its metabolites as well as maternal, placental and fetal competence in activation and deactivation of B[a]P may be critical determinants in overall fetal risk to genetic damage. Importantly, maximal sensitivity to transplacental DNA damage may be during mid-gestation. C1 UNIV TEXAS,MED BRANCH,DEPT COMMUNITY HLTH,DIV EPIDEMIOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DIV BIOSTAT,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. BIOQUAL INC,ROCKVILLE,MD 20850. RP LU, LJW (reprint author), UNIV TEXAS,MED BRANCH,DEPT PREVENT MED,DIV ENVIRONM TOXICOL,GALVESTON,TX 77555, USA. NR 73 TC 40 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1993 VL 14 IS 9 BP 1805 EP 1813 DI 10.1093/carcin/14.9.1805 PG 9 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400013 PM 8403203 ER PT J AU STEVNSNER, T BOHR, VA AF STEVNSNER, T BOHR, VA TI STUDIES ON THE ROLE OF TOPOISOMERASES IN GENERAL, GENE-SPECIFIC AND STRAND-SPECIFIC DNA-REPAIR SO CARCINOGENESIS LA English DT Article ID HAMSTER OVARY CELLS; INTERSTRAND CROSS-LINKS; EXCISION REPAIR; RIBOSOMAL-RNA; ACTIVE GENE; DHFR GENE; CHO CELLS; TRANSCRIPTION; GENOME; PROLIFERATION AB Using specific inhibitors we have assessed the role of topoisomerases I and II in DNA repair of the overall genome and in both strands of an essential gene, the dihydrofolate reductase (DHFR) gene in chinese hamster ovary (CHO) cells. In these studies we have: (1) used inhibitors of topoisomerases during the repair incubation and (2) studied the DNA repair in cells with altered levels of topoisomerase activity. When cells were allowed to repair after UV irradiation, the gene-specific DNA repair was not affected by either topoisomerase I or topoisomerase II inhibitors alone. However, when topoisomerase I and topoisomerase II inhibitors were added simultaneously the gene- and strand-specific DNA repair were markedly inhibited. In contrast, the overall genome DNA repair was only marginally affected. This suggests that topoisomerases are involved in gene-specific DNA repair and that one type may substitute for the other in the repair process. That concept is further supported by our findings using a mutant cell line with a decreased level of topoisomerase I: gene-specific DNA repair can be inhibited by a topoisomerase H inhibitor alone. By analyzing the steady-state expression of the DHFR gene we find that inhibition of repair in the DHFR gene is not ascribed to an obvious change in the messenger level. Furthermore, using agents other than UV, we observe that the inhibitors have no effect on gene-specific repair of DNA damage introduced by the chemotherapeutic agents cisplatin and nitrogen mustard. C1 NIA, MOLEC GENET LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NIA, DIV CANC TREATMENT, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 51 TC 61 Z9 63 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 SEP PY 1993 VL 14 IS 9 BP 1841 EP 1850 DI 10.1093/carcin/14.9.1841 PG 10 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400019 PM 8403208 ER PT J AU SEWALL, CH LUCIER, GW TRITSCHER, AM CLARK, GC AF SEWALL, CH LUCIER, GW TRITSCHER, AM CLARK, GC TI TCDD-MEDIATED CHANGES IN HEPATIC EPIDERMAL GROWTH-FACTOR RECEPTOR MAY BE A CRITICAL EVENT IN THE HEPATOCARCINOGENIC ACTION OF TCDD SO CARCINOGENESIS LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; PROMOTER ETHINYL ESTRADIOL; CULTURED RAT HEPATOCYTES; LIVER-REGENERATION; ESTROGEN-RECEPTOR; TUMOR PROMOTERS; PLASMA-MEMBRANE; FACTOR-ALPHA; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; GLUCOCORTICOID RECEPTOR AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent liver tumor promoter in rats, with females being more sensitive than males. The epidermal growth factor receptor (EGFR) pathway has been implicated in altered cell growth patterns induced by tumor promoters. We investigated hepatic EGFR levels in a two-stage initiation promotion model. The TCDD doses were chosen to encompass the dose range administered in a previous chronic bioassay currently used to determine the cancer potency commonly used for human health risk assessments. TCDD was administered biweekly by oral gavage to female Sprague-Dawley rats for 30 weeks following initiation by a single dose of diethylnitrosamine (DEN). TCDD-mediated decreased EGF receptor levels were demonstrated in intact but not ovariectomized animals, consistent with previous tumor data. Likewise, previous studies have shown that TCDD induces cell proliferation in intact rats but not ovariectomized rats. We report a significant dose-dependent decrease in plasma membrane EGF receptor maximum binding capacity in both initiated and non-initiated intact rats at TCDD doses equivalent to 3.5, 10.7, 35.7 and 125 ng/kg/day. There was a significant correlation between EGF receptor effects and liver TCDD concentration. The decrease in plasma membrane EGFR determined by equilibrium binding was confirmed quantitatively by EGF stimulation of EGFR autophosphorylation as well as qualitatively by immunohistochemical detection in control and treated rats. These results demonstrate that the observed down modulation of the EGFR by TCDD is ovarian-dependent and is a sensitive effect induced at dose levels associated with TCDD hepatocarcinogenicity in rodent bioassays. C1 NIEHS, MD D4-04, POB 12233, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, CHAPEL HILL, NC 27514 USA. NR 67 TC 62 Z9 62 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1993 VL 14 IS 9 BP 1885 EP 1893 DI 10.1093/carcin/14.9.1885 PG 9 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400026 PM 8403215 ER PT J AU ENOMOTO, T WEGHORST, CM WARD, JM ANDERSON, LM PERANTONI, AO RICE, JM AF ENOMOTO, T WEGHORST, CM WARD, JM ANDERSON, LM PERANTONI, AO RICE, JM TI LOW-FREQUENCY OF H-RAS ACTIVATION IN NATURALLY-OCCURRING HEPATOCELLULAR TUMORS OF C3H HENCR MICE SO CARCINOGENESIS LA English DT Article ID MOUSE-LIVER TUMORS; B6C3F1 MOUSE; K-RAS; N-NITROSODIETHYLAMINE; F344 RATS; ONCOGENES; MUTATIONS; HEPATOCARCINOGENESIS; LESIONS; GENE AB Previous reports from several laboratories have consistently shown that approximately 30% of spontaneous hepatocellular adenomas and 70-80% of spontaneous hepatocellular carcinomas found in aged B6C3F1 [C57BL/6 (liver tumor resistant) x C3H (liver tumor susceptible)] male mice contain one of three missense point mutations in codon 61 of the H-ras oncogene, CAA --> AAA, CGA or CTA. Irrespective of subline, the C3H mouse, the paternal parent strain of the B6C3F1 hybrid, is more susceptible to spontaneous liver tumorigenesis than the B6C3F1 mouse. However, the role of H-ras in the pathogenesis of hepatocellular tumors in C3H mice is less clear, as widely different frequencies of activation of this gene, but by the same point mutations in codon 61, have been reported by various laboratories. The present study was undertaken to characterize H-ras involvement in hepatocellular tumors of aged C3H/He mice from the HCI-Frederick Cancer Research and Development Center Colony (C3H/HeNCr). Oncogene activation was evaluated in 45 C3H/HeNCr hepatocellular tumors by the NIH 3T3 transfection assay, and point mutations in the H-ras oncogene were detected and characterized in DNA fragments amplified by PCR, using dot blot hybridization analysis with mutation-specific oligonucleotide probes and direct dideoxy sequencing of PCR products. The only transforming gene detected in these tumors by NIH 3T3 transfection was H-ras. Only 17% (1/6) of spontaneous carcinomas and 8% (3/39) of spontaneous adenomas contained transforming H-ras sequences, each with a point mutation in codon 61. In all four cases with H-ras mutations, mutated sequences comprised a minor fraction of total H-ras gene copies in DNA extracted from primary tumors. H-ras mutations thus appear to have arisen relatively late in the pathogenesis of the neoplasms. For comparison, sections of formalin-fixed, paraffin-embedded hepatocellular tumors that occurred in untreated B6C3F1 hybrid mice sired by C3H/HeNCr males were assayed for the same H-ras mutations by PCR and dot blot hybridization. Nine of 13 such tumors (4/6 carcinomas, 5/7 adenomas) were positive. The overall difference in frequency of H-ras codon 61 mutations in hepatocellular tumors in C3H/HeNCr (4/45) versus B6C3F1 (9/13) was highly significant (P = 0.000035, Fisher's exact test). These data indicate that point mutations in H-ras do not generally play a major or an initiating role in spontaneous hepatocarcinogenesis of inbred C3H/HeNCr mice and contrast with the high rate of ras mutations in liver tumors of the B6C3F1 hybrid. C1 NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 36 TC 12 Z9 12 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1993 VL 14 IS 9 BP 1939 EP 1944 DI 10.1093/carcin/14.9.1939 PG 6 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400034 PM 8403222 ER PT J AU FU, YM MESRI, EA YU, ZX KREITMAN, RJ PASTAN, I EPSTEIN, SE AF FU, YM MESRI, EA YU, ZX KREITMAN, RJ PASTAN, I EPSTEIN, SE TI CYTOTOXIC EFFECTS OF VASCULAR SMOOTH-MUSCLE CELLS OF THE CHIMERIC TOXIN, HEPARIN-BINDING TGF-ALPHA-PSEUDOMONAS EXOTOXIN SO CARDIOVASCULAR RESEARCH LA English DT Article DE EGF; PROLIFERATION; RESTENOSIS ID FIBROBLAST GROWTH-FACTOR; CORONARY ANGIOPLASTY; MESSENGER-RNA; FACTOR-I; RESTENOSIS; PROLIFERATION; RECEPTORS; SULFATE; PROTEOGLYCANS; ACCUMULATION AB Objective: Smooth muscle cell proliferation appears to be very important in restenosis after angioplasty. A chimeric toxin created by genetically fusing the gene encoding TGFalpha (targets the EGF receptor) to the gene encoding Pseudomonas exotoxin (PE) preferentially kills rapidly proliferating smooth muscle cells. Recently, a heparin binding EGF-like growth factor (HB-EGF) has been identified. The HB domain enhances the mitogenic activity for smooth muscle cells. The purpose of this study was to design a new chimeric toxin, having both heparin binding and EGF receptor binding function, and to determine whether it is more cytotoxic to smooth muscle cells. Methods: By recombinant DNA techniques, a new chimeric toxin, HB-TGFalpha-PE(4E)KDEL, was synthesised. Cytotoxic assays were performed by assessing the capacity to inhibit protein synthesis of rat vascular smooth muscle cells. Results: The toxin preferentially killed rapidly proliferating smooth muscle cells (p<0.025). The HB domain increased the cytotoxicity of the molecule when compared to the other chimeric toxins tested against smooth muscle cells. The cytotoxic effect of the new molecule was significantly decreased by exogenously added heparin (p<0.05). Conclusions: The presence of a heparin binding domain increases the smooth muscle cell cytotoxicity of the TGFalpha fusion toxin, perhaps because HB-TGFalpha-PE(4E)KDEL functions as a molecule with two ligands. It will be important to determine whether the greater smooth muscle cell cytotoxicity that exists in vitro will facilitate the specific targeting and killing of rapidly proliferating cells in vivo. C1 NHLBI, DIV CANC DIAGNOSIS, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP NHLBI, CARDIOL BRANCH, BLDG 10, ROOM 7B15, BETHESDA, MD 20892 USA. NR 40 TC 12 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP PY 1993 VL 27 IS 9 BP 1691 EP 1697 DI 10.1093/cvr/27.9.1691 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LX733 UT WOS:A1993LX73300022 PM 8287449 ER PT J AU DRAOUI, M MOODY, TW FATHI, Z BATTEY, J AF DRAOUI, M MOODY, TW FATHI, Z BATTEY, J TI PHORBOL ESTERS REGULATE PREPROGASTRIN-RELEASING PEPTIDE MESSENGER-RNA IN SMALL-CELL LUNG-CANCER CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BOMBESIN-LIKE PEPTIDES; NEURO-BLASTOMA CELLS; GENE-EXPRESSION; CYCLIC-AMP; TRANSCRIPTIONAL REGULATION; CARCINOMA; GROWTH; PROTEINS; IDENTIFICATION; SOMATOSTATIN AB The expression of preprogastrin-releasing peptide (GRP) mRNA was studied using human small cell lung cancer (SCLC) cells. By Northern analysis, preproGRP mRNA was stimulated by 4beta-phorbol 12-myristate 13alpha-acetate (PMA) in a concentration- and time-dependent manner in these cells. In cell line NCI-H209, the addition of 10(-6) M PMA increased a 0.9-kb mRNA after 8 h. An inactive phorbol ester, 4alpha-PMA, had little effect on preproGRP mRNA. A nuclear run-on assay indicated that 10(-6) M PMA increased preproGRP transcription 3-fold, whereas beta-actin and glyceraldehyde 3-phosphate dehydrogenase transcription was unaltered. In contrast, PMA had little effect on beta-actin mRNA expression. PMA (1 mum) in the presence of 100 mum 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), a protein kinase C inhibitor, had little effect on preproGRP mRNA. Addition of PMA after protein kinase C down-regulation did not alter preproGRP mRNA. PMA (1 mum) caused translocation of protein kinase C from the cytosol to the membrane of SCLC cells. Also, PMA (10(-6) M) stimulated and H7 (10(-4) m) reduced SCLC growth in vitro. When new synthesis of preproGRP mRNA was blocked by the addition of actinomycin D, preproGRP mRNA remained stable for 15 h. These data suggest that PMA induces transcription of GRP mRNA in SCLC cells. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,2300 EYE ST NW,WASHINGTON,DC 20037. NCI,DTP,DCT,BIOL CHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-53477] NR 37 TC 18 Z9 18 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 SEP PY 1993 VL 4 IS 9 BP 723 EP 729 PG 7 WC Cell Biology SC Cell Biology GA LW625 UT WOS:A1993LW62500003 PM 8241020 ER PT J AU PUMFORD, NR MARTIN, BM THOMASSEN, D BURRIS, JA KENNA, JG MARTIN, JL POHL, LR AF PUMFORD, NR MARTIN, BM THOMASSEN, D BURRIS, JA KENNA, JG MARTIN, JL POHL, LR TI SERUM ANTIBODIES FROM HALOTHANE HEPATITIS PATIENTS REACT WITH THE RAT ENDOPLASMIC-RETICULUM PROTEIN-ERP72 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DISULFIDE ISOMERASE; LIVER; ANTIGENS; HEPATOTOXICITY; AUTOANTIBODIES; NEOANTIGENS; EXPRESSION; CELLS; MICE; LYMPHOCYTES AB Immunoblotting studies have previously shown that serum antibodies from halothane hepatitis patients react with several liver microsomal proteins that have been modified by the trifluoroacetyl halide metabolite of halothane. In this study, an 80-kDa protein recognized by the patients' antibodies has been purified from rat liver microsomes and characterized. When the purified trifluoroacetylated 80-kDa and native 80-kDa proteins were employed as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients. Amino acid sequence analyses of several hydrolytic peptide fragments of the 80-kDa protein showed that the protein was 99 % identical to the deduced amino acid sequence of a murine cDNA of the luminal endoplasmic reticulum protein ERp72. These results indicate that trifluoroacetylated ERp72 in the liver of halothane hepatitis patients may induce immune responses against epitopes present on the covalently altered protein and those present on the native protein and may have a role in halothane hepatitis. In addition, immunoblot and immunohistochemical studies revealed that the 80-kDa protein was present in all tissues studied, but was in highest concentration in liver, adipose tissue, ovaries, and testes and was enriched in specific cells of some organs. In the future, these findings should help define the physiological function of ERp72. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N115,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,LAB SCI SECT,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 38 TC 40 Z9 40 U1 0 U2 0 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 SEP-OCT PY 1993 VL 6 IS 5 BP 609 EP 615 DI 10.1021/tx00035a004 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LY693 UT WOS:A1993LY69300004 PM 8292737 ER PT J AU HANNA, PM KADIISKA, MB JORDAN, SJ MASON, RP AF HANNA, PM KADIISKA, MB JORDAN, SJ MASON, RP TI ROLE OF METALLOTHIONEIN IN ZINC(II) AND CHROMIUM(III) MEDIATED TOLERANCE TO CARBON-TETRACHLORIDE HEPATOTOXICITY - EVIDENCE AGAINST A TRICHLOROMETHYL RADICAL-SCAVENGING MECHANISM SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID INDUCED LIPID-PEROXIDATION; RED-BLOOD-CELLS; RATS; INVITRO; INVIVO; LIVER; CYTOCHROME-P-450; METABOLISM; BROMOTRICHLOROMETHANE; INFLAMMATION AB The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed protective roles of Zn(II), Cr(III), and metallothionein (MT) against carbon tetrachloride toxicity in vivo. Hepatic MT, which is induced by Zn(II), has been proposed to protect against CCl4-induced cellular damage by scavenging the free radical metabolites formed. CCl4-induced hepatotoxicity was significantly suppressed in male Sprague-Dawley rats pretreated with a single dose of 5 mg/kg Zn(II) or Cr(III) according to standard serum assays for liver-specific enzymes, and hepatic MT was elevated after pretreatment with either Zn(II) or Cr(III). In vitro, no difference was detected in either the amount of CCl4-derived free radical metabolites formed or the rate at which they were formed by microsomes from rats pretreated 24 h in advance with 5 mg/kg Zn(II) or Cr(III). Extraction of rat liver with 2:1 chloroform/methanol 1 h after the administration of a 0.8 mL/kg intraperitoneal or intragastric dose of CCl4 also revealed no difference in the amount of trichloromethyl radical spin trapped in vivo following pretreatment with either Zn(II) or Cr(III). These results suggest that pretreatment with either Zn(II) or Cr(III) does not affect CCl4 metabolism nor does the MT significantly scavenge the trichloromethyl free radical metabolite. C1 BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. RP HANNA, PM (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 49 TC 22 Z9 23 U1 1 U2 3 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 SEP-OCT PY 1993 VL 6 IS 5 BP 711 EP 717 DI 10.1021/tx00035a017 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LY693 UT WOS:A1993LY69300017 PM 8292750 ER PT J AU LIPSCHIK, GY DOERFLER, ME KOVACS, JA TRAVIS, WD ANDRAWIS, VA LAWRENCE, MG DICHTER, JR OGNIBENE, FP SHELHAMER, JH AF LIPSCHIK, GY DOERFLER, ME KOVACS, JA TRAVIS, WD ANDRAWIS, VA LAWRENCE, MG DICHTER, JR OGNIBENE, FP SHELHAMER, JH TI LEUKOTRIENE-B4 AND INTERLEUKIN-8 IN HUMAN IMMUNODEFICIENCY VIRUS-RELATED PULMONARY-DISEASE SO CHEST LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; BRONCHOALVEOLAR LAVAGE FLUID; NONSPECIFIC INTERSTITIAL PNEUMONITIS; NECROSIS-FACTOR-ALPHA; NEUTROPHIL CHEMOTACTIC FACTORS; HUMAN ALVEOLAR MACROPHAGE; MONONUCLEAR PHAGOCYTES; POTENTIAL MECHANISM; ADJUNCTIVE THERAPY; CONTROLLED TRIAL AB Study objective: To investigate the pathogenesis of lung injury in Pneumocystis carinii pneumonia and nonspecific interstitial pneumonitis (NIP), common pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of corticosteroid therapy in P carinii pneumonia and the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis support the premise that the lung injury of P carinii pneumonia is due to the host's inflammatory response to the infection. Design: In vitro measurements on previously collected BAL fluid samples. Setting. The Clinical Center of the National Institutes of Health, a research hospital and tertiary care referral center. Patients: Five normal volunteers, 5 asymptomatic HIV-positive patients, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respiratory symptoms), and 19 HIV-positive patients with P carinii pneumonia. Measurements and results: BAL leukotriene B4 (LTB4), interleukin 8 (IL-8), and phospholipase A2 (PLA2) were measured. IL-8 and PLA2 were elevated in patients with P carinii pneumonia, and IL-8 correlated with BAL fluid absolute neutrophil count. LTB4, IL-8, and PLA2 levels were elevated in patients with NIP; LTB4 and PLA2 levels correlated with absolute neutrophil count, and IL-8 correlated with alveolar-arterial oxygen pressure difference. IL-8 was elevated in the asymptomatic HIV-positive patients, and there was a trend toward elevation of PLA2 in this group. Conclusion: IL-8 appears to play a role in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrophil chemotaxin in this disease; PLA2 may also be involved in the pathogenesis of P carinii pneumonia. Both LTB4 and IL-8 may be involved in the recruitment of neutrophils and subsequent lung injury of NIP. These data suggest that there are varying mechanisms by which inflammatory cells are recruited to the lung in different HIV-related lung diseases. C1 NCI,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,BLDG 10,RM 7B43,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NYU MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10016. NR 44 TC 49 Z9 49 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1993 VL 104 IS 3 BP 763 EP 769 DI 10.1378/chest.104.3.763 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LW517 UT WOS:A1993LW51700025 PM 8396001 ER PT J AU GILLISSEN, A ROUM, JH HOYT, RF CRYSTAL, RG AF GILLISSEN, A ROUM, JH HOYT, RF CRYSTAL, RG TI AEROSOLIZATION OF SUPEROXIDE-DISMUTASE - AUGMENTATION OF RESPIRATORY EPITHELIAL LINING FLUID ANTIOXIDANT SCREEN BY AEROSOLIZATION OF RECOMBINANT HUMAN CU++/ZN++ SUPEROXIDE-DISMUTASE SO CHEST LA English DT Article ID PULMONARY OXYGEN-TOXICITY; INTERSTITIAL LUNG-DISEASE; ALPHA-1-ANTITRYPSIN DEFICIENCY; ALVEOLAR MACROPHAGES; TRACT INFLAMMATION; ELASTASE DEFENSES; HYDROGEN-PEROXIDE; INDIVIDUALS; FIBROSIS; CATALASE AB Various human pulmonary diseases are characterized by an increased oxidant burden on the respiratory epithelial surface. As a step toward developing a therapy to augment the antioxidant defenses of respiratory epithelial lining fluid (ELF) of the human lung, we have evaluated the feasibility of aerosolizing a human protein antioxidant to the respiratory epithelial surface of an experimental animal sufficiently large to permit repetitive sampling of ELF. To accomplish this, recombinant human Cu++/Zn++ superoxide dismutase (rSOD) was aerosolized to sheep, and the levels of human superoxide dismutase (SOD) and antisuperoxide anion (O2-) capacity were quantified in ELF over time. In vitro aerosolization did not alter the specific activity of rSOD (p>0.5). In vivo aerosolization of rSOD (100 mg) to sheep (n = 7) resulted in peak amounts of human Cu++/Zn++ SOD in ELF of 3.1 +/- 0.6 mumol/L, with a parallel increase in the anti-O2- capacity of ELF. For the duration of the study (5 h), levels of SOD and anti-O2- in ELF remained elevated, with a value 50 percent of the peak at 5 h. Aerosolization of phosphate-buffered saline (n = 5) had no effect on SOD or anti-O2- levels in ELF. In animals receiving rSOD, there was no change in the specific activity of SOD recovered in ELF compared to the starting material (p>0.4). We conclude that rSOD can be delivered by aerosol to the ELF of a large animal with preservation of specific activity and that a substantial increase in both the amount of SOD and the anti-O2- capacity can be achieved for a period of time applicable to human therapy, supporting the rationale for evaluation of rSOD aerosol as an antioxidant in human pulmonary disease. C1 NHLBI,LAB ANIM MED & SURG SECT,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. NR 41 TC 25 Z9 25 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1993 VL 104 IS 3 BP 811 EP 815 DI 10.1378/chest.104.3.811 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LW517 UT WOS:A1993LW51700033 PM 8396002 ER PT J AU LENFANT, C AF LENFANT, C TI THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE VALUE FUNCTION - MEASURE FOR MEASURE SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,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 SEP PY 1993 VL 88 IS 3 BP 831 EP 831 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LV728 UT WOS:A1993LV72800002 PM 8353911 ER PT J AU NEWMAN, AB SISCOVICK, DS MANOLIO, TA POLAK, J FRIED, LP BORHANI, NO WOLFSON, SK AF NEWMAN, AB SISCOVICK, DS MANOLIO, TA POLAK, J FRIED, LP BORHANI, NO WOLFSON, SK TI ANKLE-ARM INDEX AS A MARKER OF ATHEROSCLEROSIS IN THE CARDIOVASCULAR HEALTH STUDY SO CIRCULATION LA English DT Article DE PERIPHERAL VASCULATURE; EPIDEMIOLOGY; AGING; TESTS ID PERIPHERAL ARTERIAL-DISEASE; ISCHEMIC-HEART-DISEASE; INTERMITTENT CLAUDICATION; VASCULAR-DISEASE; RISK-FACTORS; MYOCARDIAL-INFARCTION; SYSTOLIC HYPERTENSION; PREVALENCE; POPULATION; FRAMINGHAM AB Background. Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD. Methods and Results. The AAI was measured in 5084 participants greater-than-or-equal-to 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (<0.8, greater-than-or-equal-to 0.8 to <0.9, greater-than-or-equal-to 0.9 to <1.0, greater-than-or-equal-to 1.0 to <1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants <0.8, 12.4% <0.9, and 23.6% <1.0. Participants with an AAI <0.8 were more than twice as likely as those within AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P<.01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P<.01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of <1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P<.01). Conclusions. There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD. C1 MED COLL PENN,DEPT MED,PITTSBURGH,PA. UNIV WASHINGTON,DEPT MED & EPIDEMIOL,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT MED & EPIDEMIOL,BALTIMORE,MD 21205. UNIV CALIF DAVIS,SCH MED,DEPT MED,DAVIS,CA 95616. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15260. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85082, N01-HL-85079] NR 41 TC 721 Z9 756 U1 1 U2 19 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1993 VL 88 IS 3 BP 837 EP 845 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LV728 UT WOS:A1993LV72800004 PM 8353913 ER PT J AU DILSIZIAN, V PERRONEFILARDI, P ARRIGHI, JA BACHARACH, SL QUYYUMI, AA FREEDMAN, NMT BONOW, RO AF DILSIZIAN, V PERRONEFILARDI, P ARRIGHI, JA BACHARACH, SL QUYYUMI, AA FREEDMAN, NMT BONOW, RO TI CONCORDANCE AND DISCORDANCE BETWEEN STRESS-REDISTRIBUTION-REINJECTION AND REST-REDISTRIBUTION THALLIUM IMAGING FOR ASSESSING VIABLE MYOCARDIUM - COMPARISON WITH METABOLIC-ACTIVITY BY POSITRON EMISSION TOMOGRAPHY SO CIRCULATION LA English DT Article DE CORONARY ARTERY DISEASE; MYOCARDIUM; ISCHEMIA; SCINTIGRAPHY; TOMOGRAPHY ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR DYSFUNCTION; BLOOD-FLOW; OXIDATIVE-METABOLISM; FUNCTIONAL RECOVERY; TL-201 REINJECTION; BYPASS SURGERY; WALL-MOTION; REVASCULARIZATION; SCINTIGRAPHY AB Background. Stress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution-reinjection and rest-redistribution imaging provide the same information regarding myocardial viability. Methods and Results. Both stress-redistribution-reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest-redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [F-18]fluorodeoxyglucose and [O-15]water. In these patients, stress-redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity, and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%. Conclusions. These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP DILSIZIAN, V (reprint author), NIH,DEPT NUCL MED,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 39 TC 138 Z9 139 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 SEP PY 1993 VL 88 IS 3 BP 941 EP 952 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LV728 UT WOS:A1993LV72800015 PM 8353921 ER PT J AU EPSTEIN, SE SPEIR, E FINKEL, T AF EPSTEIN, SE SPEIR, E FINKEL, T TI DO ANTISENSE APPROACHES TO THE PROBLEM OF RESTENOSIS MAKE SENSE SO CIRCULATION LA English DT Editorial Material ID MUSCLE CELL-PROLIFERATION; EXTRACELLULAR ATP; INHIBITION; MIGRATION; KINETICS; INVIVO; GROWTH; INJURY RP EPSTEIN, SE (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,RM 7B15,BETHESDA,MD 20892, USA. NR 17 TC 34 Z9 34 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 SEP PY 1993 VL 88 IS 3 BP 1351 EP 1353 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LV728 UT WOS:A1993LV72800063 PM 8353896 ER PT J AU BENGE, H CSAKO, G PARL, FF AF BENGE, H CSAKO, G PARL, FF TI A 10-YEAR ANALYSIS OF REVENUES, COSTS, STAFFING, AND WORKLOAD IN AN ACADEMIC-MEDICAL-CENTER CLINICAL-CHEMISTRY LABORATORY SO CLINICAL CHEMISTRY LA English DT Article DE LABORATORY MANAGEMENT; ECONOMICS OF LABORATORY OPERATION; DIAGNOSIS-RELATED GROUP SYSTEM; SALARY; CONSUMABLES; INFLATION INDEXES ID HEALTH-CARE; VACANCY SURVEY; POSITIONS; SERVICES AB From 1980 to 1990 we found progressive increases in workload (number of billable tests; 12.1% per year), staffing [number of full-time equivalents (FTEs); 5.6% per year], ''revenues'' (gross billings; 25.8% per year), and direct cost (12.9% per year) in the clinical chemistry laboratory of a large tertiary-care university medical center. The increase in direct cost was mainly attributable to an increase in salary cost (23.7% per year), whereas the impact of increasing ''consumable'' cost was relatively small (5.3% per year). In fact, after adjustment for inflation, the consumable cost was virtually unchanged or decreased during the 10-year study period. Initially, consumables represented about 60% of the direct cost, and the remaining 40% was for salaries. After 1982/83, however, the relative contribution of consumables and salaries to direct cost gradually reversed. Because the workload grew at a higher rate than staffing, the workload per FTE increased from 1980 to 1990. This was paralleled by gradual increases in both ''revenue'' per FTE and salary per FTE in actual dollars, but by lesser increases to no increases in inflation-corrected dollars. After adjusting for inflation with different indices, the direct cost per test, the consumable cost per test, and the salary cost per test either remained unchanged or decreased in the 1980s. The findings are discussed in the context of technical advancements in laboratory testing, nationwide shortages of medical technologists, and implementation of prospective fixed-fee reimbursement practices during the study period. C1 NIH,CLIN CHEM SERV,BLDG 10,RM 2C 407,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232. NR 19 TC 15 Z9 15 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 1993 VL 39 IS 9 BP 1780 EP 1787 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA LX465 UT WOS:A1993LX46500004 PM 8375047 ER PT J AU OLDACH, DW GAYDOS, CA MUNDY, LM QUINN, TC AF OLDACH, DW GAYDOS, CA MUNDY, LM QUINN, TC TI RAPID DIAGNOSIS OF CHLAMYDIA-PSITTACI PNEUMONIA SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MONOCLONAL-ANTIBODIES; TWAR; INFECTION; CULTURE; STRAIN; FAMILY AB Two cases of Chlamydia psittaci pneumonia are presented. In each, a rapid diagnosis was made through the use of direct immunofluorescent antibody staining of respiratory secretions with monoclonal antibodies to chlamydial antigens. In one case the diagnosis was confirmed by the isolation of the causative organism from sputum and a pharyngeal swab. Chlamydial lipopolysaccharide was detectable in sputum from this patient in an enzyme immunoassay. Serological responses to C. psittaci, Chlamydia trachomatis, and Chlamydia pneumoniae were evaluated, and serological cross-reactivity was observed between each species. Rapid antigen detection systems for Chlamydia species that use commercially available reagents can be helpful in the evaluation of selected patient populations. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010; OI Oldach, David/0000-0002-8811-2562 NR 36 TC 17 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1993 VL 17 IS 3 BP 338 EP 343 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LW237 UT WOS:A1993LW23700004 PM 8218673 ER PT J AU KEMPER, CA HOSTETLER, JS FOLLANSBEE, SE RUANE, P COVINGTON, D LEONG, SS DERESINSKI, SC STEVENS, DA AF KEMPER, CA HOSTETLER, JS FOLLANSBEE, SE RUANE, P COVINGTON, D LEONG, SS DERESINSKI, SC STEVENS, DA TI ULCERATIVE AND PLAQUE-LIKE TRACHEOBRONCHITIS DUE TO INFECTION WITH ASPERGILLUS IN PATIENTS WITH AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; BRONCHIAL ASPERGILLOSIS; TRANSPLANT RECIPIENTS; AIRWAY-OBSTRUCTION; DISEASE; COMPLICATIONS; CARCINOMA; HOST AB Tracheobronchitis is an uncommon manifestation of infection due to Aspergillus species, occurring in <7% of cases of pulmonary aspergillosis. At least 58 cases of invasive aspergillus tracheobronchitis have been described since 1962. We describe four patients with AIDS, all of whom were severely immunocompromised, who had ulcerative tracheobronchitis due to Aspergillus species demonstrated histologically. Three patients had received corticosteroids or were neutropenic at presentation. At bronchoscopy, three patients had some degree of diffuse tracheobronchitis, multiple ulcerative or ''plaque-like'' inflammatory lesions, and occasionally nodules involving the mainstem and segmental bronchi. The remaining patient had a single deep ulceration of the proximal trachea. Aspergillus was isolated from biopsy specimens from all four patients. There were varied degrees of invasion of the mucosa, submucosa, and cartilage on histological examination in three patients, one of whom had evidence of disseminated aspergillosis. Two patients subsequently developed pulmonary parenchymal disease due to Aspergillus. A review of aspergillus tracheobronchitis, including a discussion of airway disease in patients infected with human immunodeficiency virus, is presented. C1 CALIF INST MED RES,SAN JOSE,CA. STANFORD UNIV,MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,STANFORD,CA 94305. AIDS CLIN RES CONSORTIUM,REDWOOD CITY,CA. DAVIES MED CTR,DEPT MED,SAN FRANCISCO,CA. CEDARS SINAI MED CTR,DEPT MED,LOS ANGELES,CA 90048. CALIF COLLABORAT TREATMENT GRP,SAN DIEGO,CA. NIAID,MYCOSES STUDY GRP,BETHESDA,MD 20892. RP KEMPER, CA (reprint author), SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,751 S BASCOM AVE,SAN JOSE,CA 95128, USA. FU PHS HHS [N01-A1-15082] NR 48 TC 78 Z9 80 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1993 VL 17 IS 3 BP 344 EP 352 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LW237 UT WOS:A1993LW23700005 PM 8218674 ER PT J AU MILLER, DL AF MILLER, DL TI ABLATION OF MEDIASTINAL PARATHYROID ADENOMAS SO CLINICAL RADIOLOGY LA English DT Letter ID AUTOTRANSPLANTATION RP MILLER, DL (reprint author), NIH,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD SEP PY 1993 VL 48 IS 3 BP 219 EP 219 DI 10.1016/S0009-9260(05)80292-2 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LW618 UT WOS:A1993LW61800021 PM 8403776 ER PT J AU KURTZMAN, HS MACDONALD, MC AF KURTZMAN, HS MACDONALD, MC TI RESOLUTION OF QUANTIFIER SCOPE AMBIGUITIES SO COGNITION LA English DT Article ID SENTENCE COMPREHENSION; EYE-MOVEMENTS; SEMANTICS; CONTEXT; ACCESS AB Various processing principles have been suggested to be governing the resolution of quantifier scope ambiguities in sentences such as Every kid climbed a tree. This paper investigates structural principles, that is, those which refer to the syntactic or semantic positions of the quantified phrases. To test these principles, the preferred interpretations for three grammatical constructions were determined in a task in which participants made speeded judgments of whether a sentence following a doubly quantified sentence was a reasonable discourse continuation of the quantified sentence. The observed preferences cannot be explained by any single structural principle, but point instead to the interaction of several principles. Contrary to many proposals, there is little or no effect of a principle that assigns scope according to the linear order of the phrases. The interaction of principles suggests that alternative interpretations of the ambiguity may be initially considered in parallel, followed by selection of the single interpretation that best satisfies the principles. These results are discussed in relation to theories of ambiguity resolution at other levels of linguistic representation. C1 UNIV SO CALIF,LOS ANGELES,CA 90089. RP KURTZMAN, HS (reprint author), NIMH,DIV NEUROSCI & BEHAV SCI,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. FU NCRR NIH HHS [2 S07 RR07047-23]; NICHD NIH HHS [NICHD R01 HD20824] NR 68 TC 66 Z9 66 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD SEP PY 1993 VL 48 IS 3 BP 243 EP 279 DI 10.1016/0010-0277(93)90042-T PG 37 WC Psychology, Experimental SC Psychology GA ME046 UT WOS:A1993ME04600003 PM 8269698 ER PT J AU DAWID, IB OTANI, H CURTISS, P TAIRA, M AF DAWID, IB OTANI, H CURTISS, P TAIRA, M TI REGULATORY INTERACTIONS DURING EMBRYOGENESIS IN XENOPUS-LAEVIS SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Article DE EMBRYONIC INDUCTION; HOMEOBOX GENES; RETINOIC ACID; CYCLOHEXIMIDE ID 9-CIS RETINOIC ACID; BONE MORPHOGENETIC PROTEIN-4; CENTRAL-NERVOUS-SYSTEM; MESODERM INDUCTION; THYROID-HORMONE; AXIS FORMATION; X-RECEPTOR; VENTRALIZING FACTOR; SPEMANN ORGANIZER; NUCLEAR RECEPTOR AB During amphibian embryogenesis, axis definition and the specification of the mesoderm and neural plate depend on cell interactions. These interactions are mediated by peptide growth factors and other diffusible molecules including retinoic acid (RA). Several genes encoding transcription factors are known to be immediate early or delayed early responses to the action of growth factors and retinoids in the embryo. By the criterion of cycloheximide (CHX) resistance, goosecoid (gsc), Xlim-1, Xbra, Mix.1, XFKH1/pintallavis/XFD1, and Xnot are immediate early response genes in mesoderm induction. Among these, gsc, Xnot and XFKH1 are superinduced by CHX, suggesting that their regulation depends in part on rapid turnover of the mRNA. RA is known to induce Xlim-1 in Xenopus embryos and to lead to anterior malformations. We show that 9-cis RA, the ligand of the RXR receptor class, is more effective than all-trans RA in generating these biological effects. RP DAWID, IB (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 71 TC 6 Z9 6 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD SEP PY 1993 VL 316 IS 9 BP 952 EP 958 PG 7 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA MB867 UT WOS:A1993MB86700011 ER PT J AU CHAN, CC COGAN, DG BUCCI, FS BARSKY, D LI, Q CRAWFORD, MA AF CHAN, CC COGAN, DG BUCCI, FS BARSKY, D LI, Q CRAWFORD, MA TI ANTERIOR CORNEAL-DYSTROPHY WITH DYSCOLLAGENOSIS (REIS-BUCKLERS TYPE) SO CORNEA LA English DT Article DE REIS-BUCKLERS CORNEAL DYSTROPHY; THIEL-BEHNKE CORNEAL DYSTROPHY; GRAYSON-WILBRANDT CORNEAL DYSTROPHY; HONEYCOMB CORNEAL DYSTROPHY; COLLAGEN TYPE-I, TYPE-III, AND TYPE-IV FIBERS AB Anterior corneal dystrophies involving Bowman's membrane and anterior stroma include several subtypes of uncertain etiology: the Reis-Buckler, Thiel-Behnke, Grayson-Wilbrandt, and ''honeycomb'' dystrophies. The clinical and pathologic features of these dystrophies overlap to such a degree that they may represent variations of the same entity. Typically, they all present symptoms beginning in childhood, have a dominant pattern of heredity, and manifest painful, recurrent corneal erosions. Some cases have also been interpreted as representing macular and granular dystrophy. In the present report, we describe a pedigree of affected patients whose corneal dystrophy shared many of the clinical and pathologic features of the Reis-Bucklers and allied subtypes but which differ from all in causing visual symptoms late in life and with minimal signs of recurrent erosion. Histopathology revealed a thickening of the anterior stroma by the addition of a partially disorganized and degenerating tissue in which collagen Type III (fetal or repair collagen) is intermixed with the normal (mature) Type I collagen in the entire stroma. This is accompanied by irregular swelling of the basal epithelial cells and hyperplasia of the basement membrane (collagen Type IV, laminin and fibronectin), suggesting an aberrant influence of the epithelium on collagen synthesis. RP CHAN, CC (reprint author), NEI,BLDG 10,RM 10N206,BETHESDA,MD 20892, USA. NR 0 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 1993 VL 12 IS 5 BP 451 EP 460 DI 10.1097/00003226-199309000-00013 PG 10 WC Ophthalmology SC Ophthalmology GA LU799 UT WOS:A1993LU79900013 PM 8306668 ER PT J AU COBB, JP CUNNION, RE DANNER, RL AF COBB, JP CUNNION, RE DANNER, RL TI NITRIC-OXIDE AS A TARGET FOR THERAPY IN SEPTIC SHOCK SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE SEPSIS; NITRIC OXIDE; ENDOTHELIUM; L-ARGININE; N(OMEGA)-NITRO-L-ARGININE; N(OMEGA)-METHYL-L-ARGININE; N(OMEGA)-AMINO-L-ARGININE; ENDOTHELIUM-DERIVED RELAXING FACTOR ID L-ARGININE; ENDOTOXIN; SYNTHASE; INHIBITION; CELLS; RAT C1 NIH,BETHESDA,MD 20892. RP COBB, JP (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143, USA. NR 20 TC 43 Z9 43 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1993 VL 21 IS 9 BP 1261 EP 1263 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA LW857 UT WOS:A1993LW85700003 PM 8370286 ER PT J AU BOULAY, JL PAUL, WE AF BOULAY, JL PAUL, WE TI HEMATOPOIETIN SUBFAMILY CLASSIFICATION BASED ON SIZE, GENE ORGANIZATION AND SEQUENCE HOMOLOGY SO CURRENT BIOLOGY LA English DT Review ID CYTOKINE RECEPTOR SUPERFAMILY; COLONY-STIMULATING FACTOR; GROWTH-FACTOR RECEPTORS; CRYSTAL-STRUCTURE; ERYTHROPOIETIN RECEPTOR; 3-DIMENSIONAL STRUCTURE; EXTRACELLULAR DOMAIN; HUMAN INTERLEUKIN-4; MOLECULAR-CLONING; IL-2 RECEPTOR C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 47 TC 53 Z9 53 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP PY 1993 VL 3 IS 9 BP 573 EP 581 DI 10.1016/0960-9822(93)90002-6 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MR373 UT WOS:A1993MR37300002 PM 15335670 ER PT J AU GERMAIN, RN AF GERMAIN, RN TI SEEING DOUBLE SO CURRENT BIOLOGY LA English DT Note ID T-CELL RECEPTOR; ANTIGEN; MOLECULES; PEPTIDES; MODEL RP GERMAIN, RN (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892, USA. NR 12 TC 18 Z9 18 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP PY 1993 VL 3 IS 9 BP 586 EP 589 DI 10.1016/0960-9822(93)90004-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MR373 UT WOS:A1993MR37300004 PM 15335672 ER PT J AU SUH, EDW VISTICA, BP CHAN, CC RABER, JM GERY, I NUSSENBLATT, RB AF SUH, EDW VISTICA, BP CHAN, CC RABER, JM GERY, I NUSSENBLATT, RB TI SPLENECTOMY ABROGATES THE INDUCTION OF ORAL TOLERANCE IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS SO CURRENT EYE RESEARCH LA English DT Article ID RETINOID-BINDING PROTEIN; MYELIN BASIC-PROTEIN; IMMUNE DEVIATION; S-ANTIGEN; CYCLOSPORIN-A; II COLLAGEN; LEWIS RATS; SUPPRESSION; UVEITIS; ENCEPHALOMYELITIS AB Oral administration of uveitogenic antigens inhibits the development of experimental autoimmune uveoretinitis (EAU) and the cellular immune response initiated by these antigens. The mechanism of oral tolerance is not completely clear, but accumulating data indicate that suppressor cells are actively involved in this process. The spleen is known to harbor suppressor cells and their precursors and the present study was aimed at testing the role of this organ in the induction of oral tolerance by S-antigen (S-AG). We report here that: (a) splenectomy abrogated the induction of oral tolerance; unlike in sham operated controls, feeding with S-Ag did not inhibit the development of EAU in splenectomized rats; (b) spenectomized rats responded with higher cellular immune responses than did sham operated controls, but feeding with S-Ag inhibited these responses in both groups of animals; (c) splenectomy also abrogated the adoptive transfer of tolerance : EAU induction was inhibited in sham operated recipients of splenocytes from S-Ag fed donors but not in the splenectomized recipients. The data thus indicate that the spleen plays an important role in the induction of oral tolerance, perhaps by acting as the site for induction and/or amplification of cells with suppressor activity. C1 NEI,IMMUNOL LAB,BLDG 10,RM 10N208,BETHESDA,MD 20892. NR 34 TC 30 Z9 31 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 SEP PY 1993 VL 12 IS 9 BP 833 EP 839 DI 10.3109/02713689309020388 PG 7 WC Ophthalmology SC Ophthalmology GA MD318 UT WOS:A1993MD31800007 PM 8261794 ER PT J AU LLOYD, AR JOHNSTON, J AF LLOYD, AR JOHNSTON, J TI CYTOKINES AND CYTOKINE RECEPTORS IN HEALTH AND DISEASE - A SUMMARY OF THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE FRONTIERS IN BASIC SCIENCES SYMPOSIUM, DECEMBER 2-3, 1992 SO CYTOKINE LA English DT Article C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP LLOYD, AR (reprint author), PRINCE HENRY HOSP,DEPT INFECT DIS,ANZAC PARADE,LITTLE BAY,NSW 2036,AUSTRALIA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 1993 VL 5 IS 5 BP 399 EP 406 DI 10.1016/1043-4666(93)90029-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA MN315 UT WOS:A1993MN31500001 PM 8142594 ER PT J AU BOCK, GH LONG, CA RILEY, ML WHITE, JD KURMAN, CC FLEISHER, TA TSOKOS, M BROWN, M SERBOUSEK, D SCHWIETERMANN, WD NELSON, DL AF BOCK, GH LONG, CA RILEY, ML WHITE, JD KURMAN, CC FLEISHER, TA TSOKOS, M BROWN, M SERBOUSEK, D SCHWIETERMANN, WD NELSON, DL TI CHARACTERIZATION OF A NEW IL-6-DEPENDENT HUMAN B-LYMPHOMA CELL-LINE IN LONG-TERM CULTURE SO CYTOKINE LA English DT Article DE IMMUNE DEFICIENCY; IL-6; IL-6 RECEPTORS; INTESTINAL LYMPHANGIECTASIA; LYMPHOMA; CELL LINE ID EPSTEIN-BARR-VIRUS; RENAL-TRANSPLANT RECIPIENTS; STIMULATORY FACTOR-II; GROWTH-FACTOR; C-MYC; INTERLEUKIN-6; EXPRESSION; IL-6; DIFFERENTIATION; SERUM C1 NCI,DCBDC,METAB BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. NIH,DEPT CLIN PATHOL,IMMUNOL SERV,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 37 TC 16 Z9 16 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 1993 VL 5 IS 5 BP 480 EP 489 DI 10.1016/1043-4666(93)90039-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA MN315 UT WOS:A1993MN31500011 PM 8142604 ER PT J AU RADKEYARROW, M BROWN, E AF RADKEYARROW, M BROWN, E TI RESILIENCE AND VULNERABILITY IN CHILDREN OF MULTIPLE-RISK FAMILIES SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID ADOLESCENTS AB Under high-risk conditions of genetic and family environmental origins, some children maintain a high level of adaptive behavior, whereas others develop serious problems. What distinguishes these children? Using measures systematically obtained in a 10-year longitudinal study, standard case studies were developed on 18 resilient children with healthy adaptation throughout development (psychiatric assessment) and on 26 troubled children with serious persistent problems. All children had family risks of affective illness in both parents and a highly chaotic and disturbed family life. Well children of well parents and well-functioning families were a comparison group. The children were preadolescent or adolescent at the time of most recent assessment. The ill and well families had similar demographic characteristics. Resilient and control children were very similar on most measures. Troubled children as a group had lower scores on the Wechsler Intelligence Scale for Children - Revised, were more often shy, had poor academic achievement, and had a history of poor peer relationships. Resilient children elicited more positive reactions from teachers, were more likely to be the favored child in the family, and had more positive self-perceptions. Profiles of each child showed competing processes of vulnerability and coping. Children used a wide range of methods for coping with parental and family pathology. Resilience appeared variably robust or fragile depending on the combinations of risks and supportive factors present and the styles of coping with stress. RP RADKEYARROW, M (reprint author), NIMH,DEV PSYCHOL LAB,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lee, Hyunjoo/D-9122-2011 NR 24 TC 60 Z9 60 U1 6 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1993 VL 5 IS 4 BP 581 EP 592 PG 12 WC Psychology, Developmental SC Psychology GA MW907 UT WOS:A1993MW90700007 ER PT J AU RICHTERS, JE MARTINEZ, PE AF RICHTERS, JE MARTINEZ, PE TI VIOLENT COMMUNITIES, FAMILY CHOICES, AND CHILDRENS CHANCES - AN ALGORITHM FOR IMPROVING THE ODDS SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article AB Data are presented concerning the early predictors of adaptational success and failure among 72 children attending their Ist years of elementary school in a violent Washington, D.C., neighborhood. Adaptational failures were defined as those children who were doing poorly or failing in school and rated by their parents as suffering clinically significant levels of behavior problems. Adaptational successes were defined as children whose performance as students was rated in the average to excellent range and whose parent-rated levels of behavior problems were within the normal range. Despite the fact that these children were being raised in violent neighborhoods, had been exposed to relatively high levels of violence in the community, and were experiencing associated distress symptoms, community violence exposure levels were not predictive of adaptational failure or success. Instead, adaptational status was systematically related to characteristics of the children's homes. More specifically, the children's chances of adaptational failure rose dramatically as a function of living in unstable and/or unsafe homes. Moreover, it was not the mere accumulation of environmental adversities that gave rise to adaptational failure in these children. Rather, it was only when such adversities contaminated or eroded the stability and/or safety levels of the children's homes that the odds of their adaptational failure increased. We argue that this erosion of the quality of the child's microsystem (i.e., family) by adversities and pressures in the exosystem (i.e., community) is not an inevitable process. Although not yet well understood, it is a process over which families have and must exercise control. The implications of these data for improving children's chances of physical, psychological, and academic survival in violent neighborhoods are considered. C1 NIMH,DEV PSYCHOL LAB,ROCKVILLE,MD. RP RICHTERS, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROOM 18-C17,ROCKVILLE,MD 20857, USA. NR 50 TC 130 Z9 132 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1993 VL 5 IS 4 BP 609 EP 627 PG 19 WC Psychology, Developmental SC Psychology GA MW907 UT WOS:A1993MW90700009 ER PT J AU TAIRA, M HAYES, WP OTANI, H DAWID, IB AF TAIRA, M HAYES, WP OTANI, H DAWID, IB TI EXPRESSION OF LIM CLASS HOMEOBOX GENE XLIM-3 IN XENOPUS DEVELOPMENT IS LIMITED TO NEURAL AND NEUROENDOCRINE TISSUES SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; MESSENGER-RNAS; DOMAIN PROTEIN; NERVOUS-SYSTEM; INSULIN GENE; HOMEODOMAIN; PITUITARY; NEURONS; EMBRYOS; POU C1 SHIMANE MED UNIV,DEPT ANAT,IZUMO,SHIMANE 693,JAPAN. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RP TAIRA, M (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 42 TC 76 Z9 77 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP PY 1993 VL 159 IS 1 BP 245 EP 256 DI 10.1006/dbio.1993.1237 PG 12 WC Developmental Biology SC Developmental Biology GA LX296 UT WOS:A1993LX29600021 PM 8103491 ER PT J AU KRISKA, AM LAPORTE, RE PETTITT, DJ CHARLES, MA NELSON, RG KULLER, LH BENNETT, PH KNOWLER, WC AF KRISKA, AM LAPORTE, RE PETTITT, DJ CHARLES, MA NELSON, RG KULLER, LH BENNETT, PH KNOWLER, WC TI THE ASSOCIATION OF PHYSICAL-ACTIVITY WITH OBESITY, FAT DISTRIBUTION AND GLUCOSE-INTOLERANCE IN PIMA-INDIANS SO DIABETOLOGIA LA English DT Article DE PHYSICAL ACTIVITY; OBESITY; FAT DISTRIBUTION; GLUCOSE INTOLERANCE; PIMA INDIANS; EXERCISE ID DEPENDENT DIABETES-MELLITUS; TOLERANCE; PREVALENCE AB The relationships between physical activity, obesity, fat distribution and glucose tolerance were examined in the Pima Indians who have the highest documented incidence of non-insulin-dependent diabetes. Fasting and 2-h post-load plasma glucose concentrations, body mass index, and waist-to-thigh circumference ratios were determined in 1054 subjects aged 15-59 years. Current (during the most recent calendar year) and historical (over a lifetime) leisure and occupational physical activity were determined by questionnaire. Current physical activity was inversely correlated with fasting and 2-h plasma glucose concentrations, body mass index and waist-to-thigh ratios for most sex-age groups even when diabetic subjects were excluded. Controlled for age, obesity and fat distribution, activity remained significantly associated with 2-h plasma glucose concentrations in males. In subjects aged 37-59 years, individuals with diabetes compared to those without reported significantly less leisure physical activity during the teenage years (median hours per week of activity, 9.1 vs 13.2 for men; 1.0 vs 2.2 for women). Controlled for body mass index, sex, age and waist-to-thigh ratio, subjects who reported low levels of historical leisure physical activity had a higher rate of diabetes than those who were more active. In conclusion, current physical activity was inversely related to glucose intolerance, obesity and central distribution of fat, particularly in males. Subjects with diabetes were currently less active and reported less historical physical activity than non-diabetic subjects. These findings suggest that activity may protect against the development of non-insulin-dependent diabetes both directly and through an influence on obesity and fat distribution. C1 NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ. RP KRISKA, AM (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15261, USA. RI Nelson, Robert/B-1470-2012; OI Kriska, Andrea/0000-0002-3522-0869 NR 22 TC 95 Z9 96 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 1993 VL 36 IS 9 BP 863 EP 869 DI 10.1007/BF00400363 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LT549 UT WOS:A1993LT54900013 PM 8405759 ER PT J AU NAVARRO, S PELLIN, A NOGUERA, R DIAZ, MP TSOKOS, M TRICHE, TJ LLOMBARTBOSCH, A AF NAVARRO, S PELLIN, A NOGUERA, R DIAZ, MP TSOKOS, M TRICHE, TJ LLOMBARTBOSCH, A TI DBL ONCOGENE EXPRESSION IN CHILDHOOD TUMORS AND TUMOR-CELL LINES SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE DBL ONCOGENE; CHILDHOOD TUMORS; NEURAL DIFFERENTIATION; EWINGS SARCOMA ID EWINGS-SARCOMA; N-MYC; AMPLIFICATION; DISTINCT; DIFFERENTIATION; PROTOONCOGENE; LYMPHOMA; ORIGIN AB We studied the expression of the dbl oncogene in the total RNA obtained from a wide spectrum of childhood tumors, including Ewing's sarcomas, peripheral neuroectodermal tumors (PNET), esthesioneuroblastomas, neuroblastomas, retinoblastomas, rhabdomyosarcomas, osteosarcomas, and synovial sarcomas. Material was obtained from primary tumors, nude mice xenografts, and tumor cell lines. Following the Northern blot technique, a single band of 2.8 kb was found in each analyzed case. Induction of neural differentiation in Ewing's sarcoma, peripheral PNET, and neuroblastoma cell lines with dibutyryl cyclic AMP did not change the expression of the dbl oncogene. We conclude that the wide expression of the dbl oncogene in these childhood tumors reduces its value as a molecular marker for their differential diagnosis; on the other hand, the dbl oncogene does not appear to be an essential molecular factor in the process of neuroectodermal differentiation of small round cell tumors of childhood. C1 UNIV VALENCIA,SCH MED,DEPT PATHOL,AVDA BLASCO IBANEZ 17,E-46010 VALENCIA,SPAIN. NCI,PATHOL LAB,BETHESDA,MD 20892. CHILDRENS HOSP,DEPT PATHOL,LOS ANGELES,CA 90027. NR 19 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 1993 VL 2 IS 3 BP 158 EP 162 DI 10.1097/00019606-199309000-00003 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA MC153 UT WOS:A1993MC15300003 PM 8287229 ER PT J AU ZHOU, J RAUSCHER, FJ BONDY, C AF ZHOU, J RAUSCHER, FJ BONDY, C TI WILMS-TUMOR (WT1) GENE-EXPRESSION IN RAT DECIDUAL DIFFERENTIATION SO DIFFERENTIATION LA English DT Article ID GROWTH FACTOR-II; FETAL KIDNEY; LOCUS; CELLS AB The Wilm's tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract, where it is thought to play a role in the differentiation of these tissues. We have used immunocytochemistry and in situ hybridization to study WT1 expression in the rat uterus during normal development and pregnancy from 0 to 20 days post coitum (p.c.). WT1 mRNA was abundant in uterine stroma from juvenile rats, but was much less abundant in uterine tissue from sexually mature rats; WT1 expression is not affected by ovariectomy or by treatment with estradiol or estradiol plus progesterone. WT1 gene was highly expressed, however, in the endometrial cells of early pregnancy. On day 6 p.c. WT1 mRNA was detected in anti-mesometrial decidual cells, and WT1 immunoreactivity was concentrated in the nuclei of these cells. All cells of fully-developed deciduoma at 7-8 days p.c. demonstrated WT1 expression. WT1 was not detected in trophoblast/placental tissues but remained abundant in the decidua basalis until parturition. The expression of WT1 was compared with insulin-like growth factor-II (IGF-II) and its receptor in the decidual since it has been shown that IGF-II gene transcription is repressed by WT1 in vitro. However, no spatiotemporal correlation in the expression of these three genes was found in differentiation of the rat decidua. In summary, these data suggest a role for WT1 in decidualization, since its expression is activated during the differentiation of uterine stromal cells into decidual cells. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. RP ZHOU, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BG 10,RM 10N262,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA 52009, CA 10817, CA 47983] NR 18 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 1993 VL 54 IS 2 BP 109 EP 114 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA LY040 UT WOS:A1993LY04000005 PM 8243887 ER PT J AU KURIE, JM BROWN, P SALK, E SCHEINBERG, D BIRRER, M DEUTSCH, P DMITROVSKY, E AF KURIE, JM BROWN, P SALK, E SCHEINBERG, D BIRRER, M DEUTSCH, P DMITROVSKY, E TI COOPERATION BETWEEN RETINOIC ACID AND PHORBOL ESTERS ENHANCES HUMAN TERATOCARCINOMA DIFFERENTIATION SO DIFFERENTIATION LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; PROTEIN KINASE-C; 13-CIS-RETINOIC ACID; MONOCLONAL-ANTIBODIES; INTERFERON ALPHA-2A; NEGATIVE REGULATION; PARIETAL ENDODERM; RIBONUCLEIC-ACID; MESSENGER-RNAS; STEM-CELLS AB This study explored cooperation between the retinoic acid (RA) and protein kinase C (PKC) pathways during differentiation of the multipotential human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1). We report here that, compared to RA treatment alone, RA combined with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced the regulated expression of the immunophenotypic differentiation markers SSEA-3, a globo-series carbohydrate, and the ganglio-series carbohydrate antigens GD2 and GD3. Northern analysis and transient transfection assays revealed that TPA co-treatment augmented the RA-induced expression and activation of the RA nuclear receptor-beta (RAR-beta), one early marker of RA response in NT2/Dl cells. This finding was extended with transient co-transfection experiments using a PKC-alpha expression vector which revealed that the PKC pathway can augment the activation of RAR-beta by RA. These experiments establish PKC as a modulator of RAR-beta expression in NT2/Dl cells. Similarly, experiments showed that RA can modulate activation of the PKC-responsive AP-1 complex, a transcription factor rapidly activated by TPA. Northern analysis and transient transfection assays revealed that, compared to TPA treatment alone, RA and TPA augmented the expression and transcriptional activity of AP-1 in NT2/D1 cells. In contrast, transient transfection assays revealed no cooperative effect between RA and TPA in HeLa cells, indicating that this effect in NT2/D1 cells is cell type-specific. In summary, these studies show that stimulation of the PKC second messenger pathway can modulate tumor differentiation and transcriptional activation of a retinoid receptor associated with RA response. C1 MEM SLOAN KETTERING CANC CTR,DEPT MED,MOLEC MED LAB,BOX 305,1275 YORK AVE,NEW YORK,NY 10021. NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD 20895. MEM SLOAN KETTERING CANC CTR,DEPT MED,HEMATOPOIET CANC IMMUNOCHEM LAB,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,PROGRAM CELL BIOL & GENET,NEW YORK,NY 10021. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. FU NCI NIH HHS [1F32CA08940-02, 1RO1-CA54494-01] NR 54 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 1993 VL 54 IS 2 BP 115 EP 122 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA LY040 UT WOS:A1993LY04000006 PM 8243888 ER PT J AU MOLINA, R OESTERREICH, S ZHOU, JL TANDON, AK CLARK, GM ALLRED, DC TOWNSEND, AJ MOSCOW, JA COWAN, KH MCGUIRE, WL FUQUA, SAW AF MOLINA, R OESTERREICH, S ZHOU, JL TANDON, AK CLARK, GM ALLRED, DC TOWNSEND, AJ MOSCOW, JA COWAN, KH MCGUIRE, WL FUQUA, SAW TI GLUTATHIONE TRANSFERASE GST PI IN BREAST-TUMORS EVALUATED BY 3 TECHNIQUES SO DISEASE MARKERS LA English DT Article DE GST-PI; BREAST CANCER ID DNA FLOW-CYTOMETRY; S-TRANSFERASE; CANCER-CELLS; PROGESTERONE RECEPTORS; NITROGEN-MUSTARD; EXPRESSION; RESISTANCE; ESTROGEN; PROGNOSIS; ELEVATION AB The glutathione transferases are involved in intracellular detoxification reactions. One of these, GSTpi, is elevated in some breast cancer cells, particularly cells selected for resistance to anticancer agents. We evaluated GSTpi expression in 60 human breast tumors by three techniques, immunohistochemistry, Northern hybridization, and Western blot analysis. There was a significant positive correlation between the three methods, with complete concordance seen in 64% of the tumors. There was strong, inverse relationship between GSTpi expression and steroid receptor status with all of the techniques utilized. In addition, there was a trend toward higher GSTpi expression in poorly differentiated tumors, but no correlation was found between tumor GSTpi content and DNA ploidy or %S-phase. GSTpi expression was also detected in adjacent benign breast tissue as well as infiltrating lymphocytes; this expression may contribute to GSTpi measurements using either Northern hybridization or Western blot analysis. These results suggest that immunohistochemistry is the method of choice for measuring GSTpi in breast tumors. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED ONCOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. HOSP CLIN BARCELONA,BARCELONA 36,SPAIN. UNIV MARYLAND,BALTIMORE,MD 21201. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA54174, CA30195] NR 39 TC 17 Z9 17 U1 0 U2 1 PU ASFRA PI EDAM PA VOORHAVEN 33, 1135 BL EDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PD SEP PY 1993 VL 11 IS 2-3 BP 71 EP 82 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA MB244 UT WOS:A1993MB24400002 PM 8261735 ER PT J AU GRIFFIN, RJ BURKA, LT AF GRIFFIN, RJ BURKA, LT TI METABOLISM AND ELIMINATION OF OXAZEPAM IN B6C3F1 AND SWISS-WEBSTER MICE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; PHARMACOKINETICS; DIAZEPAM; DISPOSITION; LORAZEPAM; URINE AB The National Toxicology Program has recently determined oxazepam to be hepatocarcinogenic in mice. To aid in the assessment of the risks associated with human use of this drug, the metabolism and elimination of oxazepam in mice were exhaustively examined in B6C3F1 and Swiss-Webster mice. In this study males were given 25, 250, and 500 mg/kg by gavage, a range that includes doses found to be carcinogenic and noncarcinogenic in the National Toxicology Program bioassay. Metabolism of oxazepam by female mice of both strains was studied following administration of 500 mg/kg. More than 90% of the recovered activity was identified. Few strain differences were detected. Females of both strains metabolize oxazepam to a slightly greater extent than do males. Dose-dependent differences were detected, but they were usually nonlinear over the range examined. The routes of elimination in mice given a single dose of oxazepam were by order of importance: fecal > urinary > expired air. Pretreatment with dosed feed for 14 days (to model autoinduction in bioassay animals) resulted in a significant shift from the fecal to the urinary route of elimination, an approximately 2-fold increase in elimination of oxazepam glucuronide, and a significant decrease in excretion of unchanged oxazepam. Results of this study indicate that following constant exposure to oxazepam, mice metabolize and eliminate oxazepam in a manner more similar to that by humans than that by naive mice. This observation enhances the significance of data obtained in the bioassay and the extrapolation of that data to predict risks to human health. C1 NIEHS,POB 12233,MD C3-02,RES TRIANGLE PK,NC 27709. NR 23 TC 14 Z9 14 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP-OCT PY 1993 VL 21 IS 5 BP 918 EP 926 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MA226 UT WOS:A1993MA22600026 PM 7902256 ER PT J AU WEISS, RB CHRISTIAN, MC AF WEISS, RB CHRISTIAN, MC TI NEW CISPLATIN ANALOGS IN DEVELOPMENT - A REVIEW SO DRUGS LA English DT Review ID BLEOMYCIN COMBINATION CHEMOTHERAPY; SOUTHWEST-ONCOLOGY-GROUP; ADVANCED OVARIAN-CANCER; HUMAN-TUMOR XENOGRAFTS; CARCINOMA CELL-LINES; ENHANCED DNA-REPAIR; PHASE-I; ANTITUMOR-ACTIVITY; PLATINUM COMPLEX; CIS-DIAMMINEDICHLOROPLATINUM AB Cisplatin was discovered to have cytotoxic properties in the 1960s, and by the end of the 1970s it had earned a place as the key ingredient in the systemic treatment of germ cell cancers. Since the early seminal work in the preclinical and clinical development of this drug, several thousand analogues have been synthesised and tested for properties that would enhance the therapeutic index of cisplatin. About 13 of these analogues have been evaluated in clinical trials, but only one (carboplatin) has provided definite advantage over cisplatin and achieved worldwide approval. However, carboplatin has afforded benefit only in reducing some cisplatin toxicities; it has not enlarged the spectrum of platinum-sensitive cancers, nor has it proved active in cisplatin-resistant cancers. The major obstacle to the efficacy of cisplatin or carboplatin is platinum resistance, either innate or acquired. The mechanisms of this resistance have been under intense study, and many of the cisplatin analogues synthesised in the past decade have been designed specifically with the hope of overcoming platinum resistance. The mechanism of the cytotoxic activity of platinum complexes has also been studied intensely. Recently synthesised analogues have been designed to interact with DNA in a manner different from cisplatin and carboplatin, with the desire of finding new structures with a superior or wider spectrum of antitumour efficacy. Most recently water soluble platinum complexes that retain antitumour activity, but that can be effectively absorbed after oral administration, have been synthesised with the goal of improving patient quality of life. Nine platinum analogues are currently in clinical trials around the world (ormaplatin [tetraplatin], oxaliplatin, DWA2114R, enloplatin, lobaplatin, CI-973 [NK-121], 254-S, JM-216 and liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (LNDDP]). Some of these analogues only represent attempts to reduce cisplatin toxicity and/or allow administration without forced hydration and diuresis, which carboplatin already does. Others are 'third generation' complexes shown to have limited or no cross-resistance with cisplatin in preclinical studies. They am being tested clinically with particular attention to this highly desirable property. Some of these complexes will undoubtedly disappear into oblivion as have most of their predecessors. It is hoped that the 1990s will see the development (and worldwide registration) of another platinum complex that represents a step forward in cancer therapy, perhaps one active in cisplatin-refractory cancers and/or capable of being administered orally. C1 UNILEVER FORSCH GESELL MBH,W-2000 HAMBURG 50,GERMANY. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP WEISS, RB (reprint author), WALTER REED ARMY MED CTR,MED ONCOL SECT,WASHINGTON,DC 20307, USA. NR 109 TC 296 Z9 300 U1 6 U2 42 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 SEP PY 1993 VL 46 IS 3 BP 360 EP 377 DI 10.2165/00003495-199346030-00003 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MA091 UT WOS:A1993MA09100003 PM 7693428 ER PT J AU EISEL, U REYNOLDS, K RIDDICK, M ZIMMER, A NIEMANN, H ZIMMER, A AF EISEL, U REYNOLDS, K RIDDICK, M ZIMMER, A NIEMANN, H ZIMMER, A TI TETANUS TOXIN LIGHT-CHAIN EXPRESSION IN SERTOLI CELLS OF TRANSGENIC MICE CAUSES ALTERATIONS OF THE ACTIN CYTOSKELETON AND DISRUPTS SPERMATOGENESIS SO EMBO JOURNAL LA English DT Article DE ACTIN; NEUROTRANSMITTER RELEASE; TESTIS; TETANUS TOXIN; TRANSGENIC MICE ID NEUROTRANSMITTER RELEASE; GENETIC ABLATION; ESCHERICHIA-COLI; NEUROTOXINS; PROMOTER; SEQUENCE; PROTEIN; SYNAPTOBREVIN; SYNAPTOSOMES; HOMOLOGY AB Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release. The tetanus toxin light chain is a metalloprotease that cleaves some members of the synaptobrevin gene family with high specificity. Here, we report the expression of a synthetic gene encoding the tetanus toxin light chain in the seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired and mature spermatozoa were completely absent. Late spermatids exhibited pleomorphic shapes and acrosomal distortions. The number of Leydig cells was greatly increased. In situ hybridization analysis revealed that the toxin acts on Sertoli cells. Affected cells exhibited an aberrant distribution of actin filaments and many cells contained large vacuoles. Our results demonstrate that tetanus toxin is active in non-neuronal cells and suggest an important function for members of the synaptobrevin gene family during the late stages of spermatogenesis. C1 BUNDESFORSCH ANSTALT VIRUSERKRANKUNGEN TIERE,INST MIKROBIOL,W-7800 TUBINGEN,GERMANY. RP ZIMMER, A (reprint author), NIMH,CELL BIOL LAB,DEV BIOL UNIT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Zimmer, Andreas/B-8357-2009; OI Eisel, Ulrich/0000-0003-4178-0384 NR 49 TC 39 Z9 40 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP PY 1993 VL 12 IS 9 BP 3365 EP 3372 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU513 UT WOS:A1993LU51300003 PM 8253064 ER PT J AU BACH, LA TSENG, LYH SWARTZ, JE RECHLER, MM AF BACH, LA TSENG, LYH SWARTZ, JE RECHLER, MM TI RAT PC12 PHEOCHROMOCYTOMA CELLS SYNTHESIZE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-6 SO ENDOCRINOLOGY LA English DT Article ID FACTOR-II; MOLECULAR-CLONING; MESSENGER-RNA; DIFFERENTIATION; SERUM AB The PC12 cell line established from a rat pheochromocytoma has been extensively studied as a model of neuronal differentiation. Insulin-like growth factor-I (IGF-I) and IGF-II are mitogenic for PC12 cells under serum-starved conditions. IGF activity is modulated by a family of six IGF-binding proteins (IGFBPs). It recently was reported that PC12 cells produced an IGFBP that had a marked preferential binding affinity for IGF-II over IGF-I. We now show that the main IGFBP produced by PC12 cells is rat IGFBP-6 and compare its properties with those of human IGFBP-6. The predominant IGFBP in medium conditioned by undifferentiated and differentiated PC12 cells migrated on sodium dodecyl sulfate-12% polyacrylamide pl electrophoresis with an apparent molecular mass of 22.5-25 kilodaltons and was recognized by polyclonal antiserum to rat IGFBP-6 by immunoblotting. Rat IGFBP-6 6 mRNA (1.4 kilobases) was detected by Northern hybridization of total RNA extracted from PC12 cells using a rat IGFBP-6 cDNA probe. Rat IGFBP-6, like hu-an IGFBP-6, is O-glycosylated; incubation with neuraminidase, fucosidase, and O-glycanase reduced its apparent molecular mass to 21 kilodaltons. Competitive binding studies of rat and human IGFBP-6 with [I-125]IGF-II and unlabeled IGF-II or IGF-I demonstrated that both IGFBPs bound IGF-II with similar affinities (K(a), 1.5-1.8 x 10(11) m-1) and bound IGF-I with -25- to 35-fold lower affinity than IGF-II. Thus, differences in amino acid sequence, such as deletion of nine amino-terminal residues (including two conserved cysteine residues) in rat IGFBP-6 compared with human IGFBP-6, do not alter its binding characteristics. PC12 cells should provide a useful system to define the regulation of IGFBP-6 expression and the role of IGFBP-6 in modulating IGF action. RP BACH, LA (reprint author), NIDDKD,GROWTH & DEV SECT,MOLEC & CELLULAR ENDOCRINOL BRANCH,BLDG 10,ROOM 8014,BETHESDA,MD 20892, USA. OI Bach, Leon/0000-0002-9062-1518 NR 29 TC 21 Z9 21 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 SEP PY 1993 VL 133 IS 3 BP 990 EP 995 DI 10.1210/en.133.3.990 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LW942 UT WOS:A1993LW94200005 PM 7689963 ER PT J AU BENVENGA, S CAHNMANN, HJ ROBBINS, J AF BENVENGA, S CAHNMANN, HJ ROBBINS, J TI CHARACTERIZATION OF THYROID-HORMONE BINDING TO APOLIPOPROTEIN-E - LOCALIZATION OF THE BINDING-SITE IN THE EXON 3-CODED DOMAIN SO ENDOCRINOLOGY LA English DT Article ID LOW-DENSITY LIPOPROTEIN; CENTRAL NERVOUS-SYSTEM; E MESSENGER-RNA; THYROXINE-BINDING; A-I; CEREBROSPINAL-FLUID; PERIPHERAL-TISSUES; RECEPTOR; BRAIN; IDENTIFICATION AB Apolipoprotein-E (apoE) has been shown by noncovalent binding and photoaffinity labeling with [I-126]T4 to possess a single L-T, binding site with a K. of about 3 x 10(7) m-1 and a relative affinity for analogs of L-T4 = D-T4 = rT3 = triodothyroacetic acid > L-T3. T4 binding was not affected by the flavonoid EMD 21388 or heparin, but was inhibited by diclofenac = mefenamic acid > furosemide. Localization of the T4 site to the N-terminal 62-amino acid region of the mature peptide coded by exon 3 was deduced from the following evidence. 1) The N-terminal 15- to 26-kilodalton (kDa) fragments (within residues 1-160 to 210), but not the approximately 10- to 11-kDa fragments (within residues approximately 220-299), were labeled by [I-125]T4. 2) Variants apoE2 and apoE4, with nonconservative mutations at positions 112 and 158 (the latter unable to interact with the apoB/E receptor), maintained the ability to bind T4. 3) Monoclonal antibodies MAb 1D7 and 3H1 (epitopes at positions 139-169 and 243-272, respectively) failed to inhibit T4 binding, but MAb 6H7 (epitope at 1-125) decreased labeling by about 24%. 4) Polymers of apoE were specifically labeled despite the interaction between amphipathic alpha-helices of the exon 4-encoded region (63-299). We conclude that apoE, as previously observed with apoA-I and apoB, possesses a T4-binding domain separate from the lipid-binding domain and distinct from both the heparin- and the cell receptor-binding sites. Thyroid hormone binding by apoE may facilitate uptake of the hormone by cells through apoB/E receptors, which are widely distributed in tissues. C1 NIDDKD,GENET & BIOCHEM BRANCH,ENDOCRINOL SECT,BETHESDA,MD 20892. NR 35 TC 17 Z9 18 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1993 VL 133 IS 3 BP 1300 EP 1305 DI 10.1210/en.133.3.1300 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LW942 UT WOS:A1993LW94200044 PM 8365370 ER PT J AU KVETNANSKY, R FUKUHARA, K PACAK, K CIZZA, G GOLDSTEIN, DS KOPIN, IJ AF KVETNANSKY, R FUKUHARA, K PACAK, K CIZZA, G GOLDSTEIN, DS KOPIN, IJ TI ENDOGENOUS GLUCOCORTICOIDS RESTRAIN CATECHOLAMINE SYNTHESIS AND RELEASE AT REST AND DURING IMMOBILIZATION STRESS IN RATS SO ENDOCRINOLOGY LA English DT Article ID SYMPATHETIC NERVOUS-SYSTEM; ADRENALECTOMIZED RATS; PHYSIOLOGICAL SIGNIFICANCE; ELECTROCHEMICAL DETECTION; LIQUID-CHROMATOGRAPHY; LOCUS COERULEUS; CONSCIOUS RATS; PLASMA-LEVELS; NOREPINEPHRINE; ACTH AB Cardiovascular and metabolic adjustments during stress involve participation of the sympatho-adrenal and hypothalamic-pituitary-adrenocortical systems, which interact at several levels. The present study investigated the effects of removal of endogenous glucocorticoids on indices of norepinephrine release and metabolism and of catecholamine biosynthesis in sympathetic nerves, at baseline and in response to immobilization stress (IMMO) in rats. Plasma levels of the catecholamine precursor dihydroxyphenylalanine, norepinephrine (NE), the NE metabolites dihydroxyphenylglycol and methoxyhydroxyphenylglycol, dopamine, and the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid were measured in adrenalectomized, adrenal-medullectomized, or sham-operated conscious rats, with or without glucocorticoid treatment (25 mg/kg . 24 h cortisol for 7 days by osmotic minipumps), at rest and after 5, 20, 60, and 120 min of IMMO. Adrenalectomy eliminated plasma levels of epinephrine and corticosterone and augmented IMMO-induced increments in levels of NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, dihydroxyphenylalanine, dihydroxyphenylacetic acid, and homovanillic acid. Adrenalmedullectomy reduced plasma epinephrine, but not corticosterone, to undetectable levels at baseline and did not augment stress-induced responses of any of the measured compounds. Cortisol administration (plasma levels approximately 600 pmol/ml) reversed the augmentation of catecholaminergic responses in adrenalectomized rats. The results indicate that adrenalectomy stimulates several aspects of sympatho-neural function, including stress-induced increments in NE release, reuptake, metabolism, and turnover and in catecholamine biosynthesis. This augmentation was absent in adreno-medullectomized rats, indicating that the loss of adrenomedullary hormones after adrenalectomy does not appear to contribute to the augmentation. Since cortisol treatment reversed or prevented this augmentation, loss of feedback inhibition by endogenous glucocorticoids appears to be the basis of the enhanced responses. Thus, the results suggest that endogenous glucocorticoids restrain responses of catecholamine turnover, synthesis, release, reuptake, and metabolism in sympathetic nerves in this stress model. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N262,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,CS-80936 BRATISLAVA,CZECHOSLOVAKIA. NR 58 TC 154 Z9 157 U1 0 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1993 VL 133 IS 3 BP 1411 EP 1419 DI 10.1210/en.133.3.1411 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LW942 UT WOS:A1993LW94200059 PM 8396019 ER PT J AU DORN, LD CHROUSOS, GP AF DORN, LD CHROUSOS, GP TI THE ENDOCRINOLOGY OF STRESS AND STRESS SYSTEM DISORDERS IN ADOLESCENCE SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; POTENTIAL CLINICAL IMPLICATIONS; CUSHINGS-DISEASE; BEHAVIORAL HOMEOSTASIS; INDUCED INHIBITION; HORMONE-SECRETION; DELAYED MENARCHE; ANOREXIA-NERVOSA; NEGATIVE AFFECT C1 NIMH,BLDG 10 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. NR 71 TC 14 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1993 VL 22 IS 3 BP 685 EP 700 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LY546 UT WOS:A1993LY54600015 PM 8243455 ER PT J AU EDDY, M AF EDDY, M TI THE USE OF TRANSGENIC MICE FOR ENVIRONMENTAL-HEALTH RESEARCH SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article RP EDDY, M (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL GRP,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 4 Z9 4 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 SEP PY 1993 VL 101 IS 4 BP 298 EP 300 DI 10.2307/3431438 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MC528 UT WOS:A1993MC52800005 PM 8275985 ER PT J AU DIETER, MP AF DIETER, MP TI FATE, TRANSPORT, AND INTERACTIONS OF METALS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP DIETER, MP (reprint author), NIEHS,MD WC-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 1993 VL 101 IS 4 BP 344 EP 345 DI 10.2307/3431445 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MC528 UT WOS:A1993MC52800012 PM 7903938 ER PT J AU TOLO, KA LITTLE, RE AF TOLO, KA LITTLE, RE TI OCCASIONAL BINGES BY MODERATE DRINKERS - IMPLICATIONS FOR BIRTH OUTCOMES SO EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; BINGE DRINKING; PREGNANCY; BIRTH OUTCOMES; BIRTH-WEIGHT; INTRAUTERINE GROWTH RETARDATION AB We investigated the effects of occasional alcohol binges on birth outcomes in a cohort of live singletons born to 709 moderate drinkers recruited from a Seattle, WA, health maintenance organization before their sixth month of pregnancy. We compared infants of women with one or more binges in the month before pregnancy or in the first two trimesters with those whose mothers reported no binges in either period. Mean values of birthweight, length, head circumference, gestational age, intrauterine growth, and Apgar scores did not differ notably between the two groups. The risk of having an adverse neonatal discharge diagnosis initially appeared lower in infants of binging mothers, but this difference vanished after recategorization of the variable and control for confounding. Our results indicate that occasional binges, during a broad window of exposure and among otherwise moderate drinkers, do not adversely affect the birth outcomes examined here. RP TOLO, KA (reprint author), NIEHS,EPIDEMIOL BRANCH,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NICHD NIH HHS [HD 14689] NR 0 TC 21 Z9 22 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1993 VL 4 IS 5 BP 415 EP 420 DI 10.1097/00001648-199309000-00006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MB862 UT WOS:A1993MB86200006 PM 8399689 ER PT J AU WEISS, SRB POST, RM SOHN, E BERGER, A LEWIS, R AF WEISS, SRB POST, RM SOHN, E BERGER, A LEWIS, R TI CROSS-TOLERANCE BETWEEN CARBAMAZEPINE AND VALPROATE ON AMYGDALA-KINDLED SEIZURES SO EPILEPSY RESEARCH LA English DT Article DE ANTICONVULSANT; TOLERANCE; KINDLING; VALPROATE; CARBAMAZEPINE ID ANTICONVULSANT DRUGS DIPHENYLHYDANTOIN; BENZODIAZEPINE BINDING-SITES; DI-NORMAL-PROPYLACETATE; ETHANOLAMINE-O-SULFATE; SODIUM VALPROATE; RAT-BRAIN; CONTINGENT TOLERANCE; GABA-METABOLISM; ACID; INHIBITION AB Carbamazepine and valproate are two clinically used anticonvulsants which are also effective in the treatment of manic-depressive illness. Although the biochemical profiles of these drugs are markedly different, some mechanisms in common may be implied by their partially overlapping spectrum of therapeutic efficacy in seizure and affective disorders. Further evaluation of common biological targets of these agents was attempted by determining whether cross-tolerance would occur to the anticonvulsant effects of carbamazepine and valproate on amygdala-kindled seizures. It had previously been shown that tolerance to carbamazepine's anticonvulsant effects on amygdala-kindled seizures occurs only with contingent drug administration, i.e., it occurs only when the drug is injected before the kindling stimulation, and not when the drug is given after the seizure. In the current studies, rats that were made tolerant to carbamazepine showed cross-tolerance to valproate. Kindled rats given carbamazepine after each seizure stimulation (i.e., non-tolerant controls) did not show tolerance to valproate's anticonvulsant effects, indicating that the cross-tolerance between carbamazepine and valproate was also contingent. The clinical implications and potential common biochemical target mechanisms of the cross-tolerance between carbamazepine and valproate deserve further investigation. RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10-3N212,BETHESDA,MD 20892, USA. NR 59 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 1993 VL 16 IS 1 BP 37 EP 44 DI 10.1016/0920-1211(93)90037-8 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA LZ567 UT WOS:A1993LZ56700005 PM 8243437 ER PT J AU THEODORE, WH LEIDERMAN, D GAILLARD, W KHAN, I REEVES, P LLOYDHONTZ, K AF THEODORE, WH LEIDERMAN, D GAILLARD, W KHAN, I REEVES, P LLOYDHONTZ, K TI THE EFFECT OF NALOXONE ON CEREBRAL BLOOD-FLOW AND GLUCOSE-METABOLISM IN PATIENTS WITH COMPLEX PARTIAL SEIZURES SO EPILEPSY RESEARCH LA English DT Article DE CEREBRAL BLOOD FLOW; GLUCOSE METABOLISM; NALOXONE; COMPLEX PARTIAL SEIZURES ID POSITRON EMISSION TOMOGRAPHY; TEMPORAL-LOBE EPILEPSY; MU-OPIATE RECEPTORS; ENDOGENOUS OPIOIDS; RAT; DEPRESSION; MORPHINE AB We used positron emission tomography With [O-15]water and [F-18]fluoro-2-deoxyglucose (FDG) to study the effect of naloxone on cerebral blood flow (CBF) and glucose metabolism (LCMRglc) in patients with complex partial seizures. There was no effect on glucose metabolism, but blood flow was reduced 7-12% 45-60 min after infusion of 1 mg/kg naloxone, as was the degree of lateral temporal CBF asymmetry in patients with > 10% baseline hypoperfusion. Endogenous opiates are involved in regulation of human CBF, and possibly in hypoperfusion in epileptic foci. Since [F-18]FDG PET measures mean LCMRglc over the tracer uptake and scanning periods, it is inferior to [O-15]H2O PET for detecting drug effects which may be time dependent. C1 NIH,CTR CLIN,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. RP THEODORE, WH (reprint author), NINCDS,CLIN EPILEPSY SECT,BLDG 10,ROOM 5C-205,BETHESDA,MD 20892, USA. NR 18 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 1993 VL 16 IS 1 BP 51 EP 54 DI 10.1016/0920-1211(93)90039-A PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA LZ567 UT WOS:A1993LZ56700007 PM 8243439 ER PT J AU ORTALDO, J AF ORTALDO, J TI CELL-MEDIATED CYTOTOXICITY SO EUROPEAN CYTOKINE NETWORK LA English DT Editorial Material RP ORTALDO, J (reprint author), NCI,FCRDC,BRMP,EXPTL IMMUNOL LAB,FREDERICK,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP-OCT PY 1993 VL 4 IS 5 BP 383 EP 384 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA MM651 UT WOS:A1993MM65100009 PM 7906958 ER PT J AU GABELLI, C BILATO, C SANTAMARINAFOJO, S MARTINI, S BREWER, HB CREPALDI, G BAGGIO, G AF GABELLI, C BILATO, C SANTAMARINAFOJO, S MARTINI, S BREWER, HB CREPALDI, G BAGGIO, G TI HETEROZYGOUS APOLIPOPROTEIN-C-II DEFICIENCY - LIPOPROTEIN AND APOPROTEIN PHENOTYPE AND RSAI RESTRICTION ENZYME POLYMORPHISM IN THE APO-C-II(PADOVA) KINDRED SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE APOLIPOPROTEIN-C-II; CHYLOMICRONS; HYPERCHYLOMICRONEMIA; LIPOPROTEIN LIPASE; TYPE-I HYPERLIPOPROTEINEMIA ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; FAMILIAL HYPERCHYLOMICRONEMIA; GENE; MUTATION; HYPERTRIGLYCERIDEMIA; PATIENT; PROTEINS; LIPASE; SERUM; CHROMOSOME-19 AB Deficiency of apolipoprotein C-II (apo C-II), the cofactor for lipoprotein lipase, results in the familial chylomicronaemia syndrome characterized by severe hypertriglyceridaemia and fasting chylomicronaemia. To investigate the biochemical features of the heterozygous state for apo C-II deficiency, we characterized the lipid, lipoprotein and apolipoprotein profiles in 18 relatives of two affected individuals (brother and sister) homozygous for the apo C-II(Padova) gene defect which results in the synthesis of a truncated 36 amino acid apolipoprotein. Carrier status was established in first degree relatives as well as in seven nonobligate heterozygotes by restriction enzyme analysis of amplified apo C-II genomic DNA using RsaI. No significant differences in lipid, lipoprotein and apo C-II levels were observed in heterozygotes when compared to unaffected family members. Thus, in this study, the carrier state was not associated with hypertriglyceridaemia or reduced plasma levels of apo C-II. However, analysis of amplified DNA from members of the apo C-II(Padova) kindred by digestion with the enzyme RsaI, which identifies the mutant apo C-II, permitted the identification of heterozygous family members which could not be recognized by measuring either fasting triglycerides or plasma apo C-II levels. This study provides further evidence that apo C-II deficiency syndrome is a heterogeneous disease not only at the molecular level but also on the clinical ground with variable phenotypic expression in heterozygous individuals from different kindreds. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RP GABELLI, C (reprint author), UNIV PADUA,DEPT INTERNAL MED,VIA GIUSTINIANI 2,I-35128 PADUA,ITALY. NR 48 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD SEP PY 1993 VL 23 IS 9 BP 522 EP 528 DI 10.1111/j.1365-2362.1993.tb00960.x PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA LW666 UT WOS:A1993LW66600003 PM 7902280 ER PT J AU BENJAMIN, J BENJAMIN, M AF BENJAMIN, J BENJAMIN, M TI PANIC DISORDER MASQUERADING AS PREECLAMPSIA SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Note DE PANIC DISORDER; PREECLAMPSIA; IMIPRAMINE; ANXIETY AB Panic disorder is a specific psychiatric entity with specific and successful treatments. A parturient patient with sudden hypertension, hyperreflexia and headache was diagnosed with pre-eclampsia and treated with magnesium sulphate. Further attacks after discharge were recognized as panic attacks, and resolved with the anti-depressant imipramine. C1 BEN GURION UNIV NEGEV,DIV PSYCHIAT,BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,DIV OBSTET & GYNECOL,BEER SHEVA,ISRAEL. RP BENJAMIN, J (reprint author), NIMH,CLIN SCI LAB,NIH CLIN CTR 10-3D41,ROCKVILLE,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD SEP PY 1993 VL 51 IS 1 BP 81 EP 82 DI 10.1016/0028-2243(93)90195-I PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ME741 UT WOS:A1993ME74100013 PM 8282146 ER PT J AU PAUL, IA BASILE, AS ROJAS, E YOUDIM, MBH DECOSTA, B SKOLNICK, P POLLARD, HB KUIJPERS, GAJ AF PAUL, IA BASILE, AS ROJAS, E YOUDIM, MBH DECOSTA, B SKOLNICK, P POLLARD, HB KUIJPERS, GAJ TI SIGMA-RECEPTORS MODULATE NICOTINIC RECEPTOR FUNCTION IN ADRENAL CHROMAFFIN CELLS SO FASEB JOURNAL LA English DT Article DE CHROMAFFIN CELLS; CALCIUM FLUORESCENCE; KINETIC DATA ID CENTRAL NERVOUS-SYSTEM; GUINEA-PIG BRAIN; NEUROPEPTIDE-Y; BINDING-SITES; ACETYLCHOLINE-RECEPTOR; ANTIPSYCHOTIC-DRUGS; RAT-BRAIN; CATECHOLAMINE SECRETION; SELECTIVE LIGAND; IMMUNE-SYSTEMS AB Neither the physiological function of sigma (sigma) receptors nor the cellular mechanism responsible for the pharmacological effects of sigma receptor ligands is known. We now report that sigma receptor ligands noncompetitively inhibit nicotine-stimulated catecholamine release from bovine adrenal chromaffin cells in a concentration-dependent and reversible manner. The rank order of potency of ligands to inhibit nicotine-stimulated catecholamine release is significantly correlated (P < 0.005) with that observed in radioligand binding assays selective for the sigma1 receptor subtype. This naltrexone-insensitive effect is paralleled by an inhibition of nicotine-stimulated increases in [Ca2+]i. Sigma ligands were without effect on catecholamine release or [Ca2+]i in the absence of nicotine. In addition, nicotine accelerated the association of the sigma receptor selective radioligand, [H-3](+)pentazocine, to adrenal medullary homogenates while having no effect on the rate of ligand dissociation, consistent with a sigma ligand binding site closely associated with and allosterically modulated by the nicotinic acetylcholine receptor. Thus, the actions of agonists at the nicotinic acetylcholine receptor in bovine chromaffin cells are modulated by sigma1 receptor selective ligands. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NR 41 TC 35 Z9 36 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1993 VL 7 IS 12 BP 1171 EP 1178 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA LW817 UT WOS:A1993LW81700012 PM 8375616 ER PT J AU WANG, WL CONE, EJ ZACNY, J AF WANG, WL CONE, EJ ZACNY, J TI IMMUNOASSAY EVIDENCE FOR FENTANYL IN HAIR OF SURGERY PATIENTS SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE FENTANYL; HAIR ANALYSIS; IMMUNOASSAY; ENVIRONMENTAL CONTAMINATION ID TESTING HUMAN-HAIR; RADIOIMMUNOASSAY; PLASMA; ABUSE; ANALOGS; DRUGS; URINE AB Head hair samples obtained from surgery patients who received fentanyl during anesthesia were analyzed by immunoassay for the presence of fentanyl. Thirteen hair samples were collected from patients following intravenous administration of 1-6 mg of fentanyl. Additional hair samples were collected following the administration of 0.18 and 0.38 mg of sufentanil to 2 patients. The elapsed time after drug administration for all patients ranged from 7 to 273 days. Twenty control hair samples also were collected from staff members who reported no surgery or anesthesia during the previous year. All samples were initially washed with methanol, followed by extraction with methanol and reconstitution in citrate buffer. Analysis of wash and extract fractions was performed by radioimmunoassay (Coat-A-Count Fentanyl assay). Segmental analysis was performed on the surgery patients' hair samples. Eight of the fentanyl patients' hair samples contained fentanyl concentrations (equivalents) of 0.13-0.48 ng/10 mg of hair in the 'root' end. Fentanyl concentrations in the 'tip' segment were lower than those found in the 'root' segment with the exception of 1 subject whose hair sample had been collected only 7 days after surgery. The remaining 5 patients had fentanyl concentrations similar to those determined for the control subjects hair samples (0-0.08 ng/10 mg, n = 19): No correlation between hair fentanyl concentration and administered dose was found for the 13 fentanyl subjects. Both sufentanil subjects' hair samples tested negative. One control subject who had experienced environmental exposure to fentanyl had a fentanyl concentration of 0.29 ng/10 mg in the extract and 0.63 ng/10 mg in the wash fraction. Overall, it was concluded that hair analysis for fentanyl provided convincing evidence of past exposure to the drug. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. UNIV CHICAGO,DEPT ANESTHESIA & CRIT CARE,CHICAGO,IL 60637. NR 20 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD SEP PY 1993 VL 61 IS 1 BP 65 EP 72 DI 10.1016/0379-0738(93)90250-E PG 8 WC Medicine, Legal SC Legal Medicine GA MB582 UT WOS:A1993MB58200007 PM 8225140 ER PT J AU METZ, DC KUCHNIO, M FRAKER, DL VENZON, DJ JAFFE, G JENSEN, RT STETLERSTEVENSON, M AF METZ, DC KUCHNIO, M FRAKER, DL VENZON, DJ JAFFE, G JENSEN, RT STETLERSTEVENSON, M TI FLOW-CYTOMETRY AND ZOLLINGER-ELLISON SYNDROME - RELATIONSHIP TO CLINICAL COURSE SO GASTROENTEROLOGY LA English DT Article ID PANCREATIC ENDOCRINE TUMORS; PARAFFIN-EMBEDDED TISSUE; ISLET CELL TUMORS; DNA DISTRIBUTION PATTERN; PROLIFERATIVE ACTIVITY; NEUROENDOCRINE TUMORS; CARCINOID-TUMORS; CANCER; GASTRINOMAS; SURVIVAL C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892. NCI,DEPT SURG,BETHESDA,MD 20892. NCI,DEPT STAT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 83 TC 22 Z9 22 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 SEP PY 1993 VL 105 IS 3 BP 799 EP 813 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV382 UT WOS:A1993LV38200020 PM 8359651 ER PT J AU DIBISCEGLIE, AM HOOFNAGLE, JH KRAWCZYNSKI, K AF DIBISCEGLIE, AM HOOFNAGLE, JH KRAWCZYNSKI, K TI CHANGES IN HEPATITIS-C VIRUS-ANTIGEN IN LIVER WITH ANTIVIRAL THERAPY SO GASTROENTEROLOGY LA English DT Article ID RECOMBINANT INTERFERON-ALFA; CONTROLLED TRIAL C1 CTR DIS CONTROL,HEPATITIS BRANCH,ATLANTA,GA 30333. RP DIBISCEGLIE, AM (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 9C 103B,BETHESDA,MD 20892, USA. NR 11 TC 78 Z9 77 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 SEP PY 1993 VL 105 IS 3 BP 858 EP 862 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV382 UT WOS:A1993LV38200027 PM 7689520 ER PT J AU MULLEN, KD BASILE, AS AF MULLEN, KD BASILE, AS TI BENZODIAZEPINE-RECEPTOR ANTAGONISTS AND HEPATIC-ENCEPHALOPATHY - WHERE DO WE STAND SO GASTROENTEROLOGY LA English DT Editorial Material ID ANIMAL-MODEL; LIGANDS; FLUMAZENIL; COMPLEX; GABA C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD. RP MULLEN, KD (reprint author), CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,DEPT MED,DIV GASTROENTEROL,2500 METROHLTH DR,CLEVELAND,OH 44109, USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1993 VL 105 IS 3 BP 937 EP 940 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV382 UT WOS:A1993LV38200038 PM 8395446 ER PT J AU RANJAN, M TAFURI, SR WOLFFE, AP AF RANJAN, M TAFURI, SR WOLFFE, AP TI MASKING MESSENGER-RNA FROM TRANSLATION IN SOMATIC-CELLS SO GENES & DEVELOPMENT LA English DT Article DE MESSENGER RNA TRANSCRIPTION; MESSENGER RNA TRANSLATION; Y-BOX PROTEINS; SOMATIC CELLS; MASKED MATERNAL MESSENGER RNA; COLD SHOCK DOMAIN ID OOCYTE-SPECIFIC PROTEINS; 5S RIBOSOMAL-RNA; XENOPUS-OOCYTES; TRANSCRIPTION FACTOR; BINDING-PROTEINS; COLD SHOCK; ESCHERICHIA-COLI; DNA-BINDING; RIBONUCLEOPROTEIN-PARTICLES; DEVELOPMENTAL REGULATION AB We present evidence for a role for Y-box proteins in both mRNA transcription and translation. We have expressed an oocyte-specific RNA-binding protein (FRGY2) in somatic cells. This protein is normally found together with mRNA in large amounts within the masked maternal mRNA storage particles of Xenopus laevis oocytes. Masked maternal mRNA is believed to be translationally repressed during oogenesis and is stored within ribonucleoprotein storage particles for subsequent use during embryogenesis. Surprisingly, FRGY2 is not only found to direct the accumulation of mRNA from promoters containing binding sites for the protein but also to selectively repress translation of the same mRNA. Thus, the role of FRGY2 in the transcription and storage of maternal mRNA is similar to that of the transcription factor TFIIIA in the transcription and storage of 5S rRNA from the oocyte type 5S rRNA genes. RP RANJAN, M (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 48 TC 121 Z9 122 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1993 VL 7 IS 9 BP 1725 EP 1736 DI 10.1101/gad.7.9.1725 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA LW555 UT WOS:A1993LW55500008 PM 8370522 ER PT J AU BATEMAN, JB KOJIS, T HEINZMANN, C KLISAK, I DIEP, A CARPER, D NISHIMURA, C MOHANDAS, T SPARKES, RS AF BATEMAN, JB KOJIS, T HEINZMANN, C KLISAK, I DIEP, A CARPER, D NISHIMURA, C MOHANDAS, T SPARKES, RS TI MAPPING OF ALDOSE REDUCTASE GENE-SEQUENCES TO HUMAN CHROMOSOME-1, CHROMOSOME-3, CHROMOSOME-7, CHROMOSOME-9, CHROMOSOME-11 AND CHROMOSOME-13 SO GENOMICS LA English DT Article ID INSITU HYBRIDIZATION; NUCLEOTIDE-SEQUENCE; HUMAN ALDEHYDE; MYOINOSITOL; SUPERFAMILY; ASSIGNMENT; NEUROPATHY; FRAGMENTS; SORBITOL; CLONING C1 NATL INST HLTH, NATL CHILDRENS MED RES CTR, DEPT PEDIAT PHARMACOL, TOKYO 154, JAPAN. UNIV CALIF LOS ANGELES, SCH MED, DEPT OPHTHALMOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, HARBOR MED CTR, DIV MED GENE, TORRANCE, CA 90502 USA. NEI, MECHANISM OCULAR DIS LAB, BETHESDA, MD 20892 USA. RP BATEMAN, JB (reprint author), UNIV CALIF LOS ANGELES, CTR HLTH SCI,SCH MED,JULES STEIN EYE INST, DORIS STEIN EYE RES CTR, CTR VIS GENET, LOS ANGELES, CA 90024 USA. FU NEI NIH HHS [EY08282] NR 24 TC 13 Z9 13 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 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1993 VL 17 IS 3 BP 560 EP 565 DI 10.1006/geno.1993.1372 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LX233 UT WOS:A1993LX23300005 PM 8244370 ER PT J AU LI, SSL SHARIEF, FS AF LI, SSL SHARIEF, FS TI THE PROSTATIC ACID-PHOSPHATASE (ACPP) GENE IS LOCALIZED TO HUMAN CHROMOSOME-3Q21-Q23 SO GENOMICS LA English DT Note RP LI, SSL (reprint author), NIEHS,NATL TOXICOL PROGRAM,GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 6 Z9 7 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 SEP PY 1993 VL 17 IS 3 BP 765 EP 766 DI 10.1006/geno.1993.1403 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LX233 UT WOS:A1993LX23300036 PM 8244395 ER PT J AU BOYD, NR WINDSOR, RA AF BOYD, NR WINDSOR, RA TI A META-EVALUATION OF NUTRITION EDUCATION INTERVENTION RESEARCH AMONG PREGNANT-WOMEN SO HEALTH EDUCATION QUARTERLY LA English DT Article ID BIRTH-WEIGHT; PROGRAM; GAIN; HEALTH; FOOD AB Inadequate nutrition during pregnancy retards human fetal growth and increases the risk of delivering a low birthweight (LBW) infant. Some studies place particular emphasis on reducing LBW through improved nutrition. Consensus documents have strongly recommended intense nutrition education programs for patients at risk. Despite this well-defined need few methodologically rigorous studies have been conducted to evaluate the behavioral impact of nutrition education for pregnant patients. Criteria are recommended in the following areas: (1) research design, (2) sample size and power, (3) specification of population characteristics, (4) measurement quality, and (5) replication. The methodological quality of completed evaluations are reviewed using these criteria. The authors advocate guidelines for future investigators for conducting rigorous trials in this critical public health area. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NHLBI,BETHESDA,MD 20892. NR 42 TC 13 Z9 13 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD FAL PY 1993 VL 20 IS 3 BP 327 EP 345 DI 10.1177/109019819302000305 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LU383 UT WOS:A1993LU38300007 PM 8307758 ER PT J AU MCLEROY, KR STECKLER, AB SIMONSMORTON, B GOODMAN, RM GOTTLIEB, N BURDINE, JN AF MCLEROY, KR STECKLER, AB SIMONSMORTON, B GOODMAN, RM GOTTLIEB, N BURDINE, JN TI SOCIAL-SCIENCE THEORY IN HEALTH-EDUCATION - TIME FOR A NEW MODEL SO HEALTH EDUCATION RESEARCH LA English DT Editorial Material ID PERSPECTIVE; COMMUNITY; SMOKING C1 UNIV N CAROLINA,DEPT HLTH BEHAV & HLTH EDUC,CHAPEL HILL,NC 27599. NICHHD,BETHESDA,MD 20852. UNIV S CAROLINA,SCH PUBL HLTH,DEPT HLTH PROMOT & EDUC,COLUMBIA,SC 29208. UNIV TEXAS,DEPT KINESIOL & HLTH,AUSTIN,TX 78712. LEHIGH VALLEY HOSP,ALLENTOWN,PA 18103. RP MCLEROY, KR (reprint author), UNIV N CAROLINA,DEPT PUBL HLTH EDUC,GREENSBORO,NC 27412, USA. RI Burdine, James/C-9011-2015 OI Burdine, James/0000-0002-9164-7402 NR 31 TC 47 Z9 47 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD SEP PY 1993 VL 8 IS 3 BP 305 EP 312 PG 8 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA MD304 UT WOS:A1993MD30400001 ER PT J AU GALLUCCI, WT BAUM, A LAUE, L RABIN, DS CHROUSOS, GP GOLD, PW KLING, MA AF GALLUCCI, WT BAUM, A LAUE, L RABIN, DS CHROUSOS, GP GOLD, PW KLING, MA TI SEX-DIFFERENCES IN SENSITIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS SO HEALTH PSYCHOLOGY LA English DT Note DE SEX DIFFERENCES; STRESS; PITUITARY-ADRENOCORTICAL RESPONSE ID CORONARY HEART-DISEASE; FEMALE RATS; STRESS RESPONSES; VASOPRESSIN; CORTICOSTERONE; HORMONE AB Two studies examined sex differences in responsiveness of the hypothalamic-pituitary-adrenal cortical axis, a major component of the stress response. The first measured pituitary-adrenal responses to ovine corticotropin-releasing hormone (oCRH) in 24 healthy men and 19 healthy women. Plasma adrenocorticotropin hormone (ACTH) responses to oCRH were significantly greater among women than among men. In contrast, cortisol concentrations were similar in both groups, though elevations were more prolonged in women. Differences in corticotropin-releasing activity between men and women may help account for these findings; such differences in central components of the stress response might play a role in the known epidemiological differences in diseases of stress system dysregulation between men and women. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 21 TC 90 Z9 91 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 1993 VL 12 IS 5 BP 420 EP 425 DI 10.1037//0278-6133.12.5.420 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA NL891 UT WOS:A1993NL89100013 PM 8223368 ER PT J AU DECHESNE, CJ WINSKY, L MONIOT, B RAYMOND, J AF DECHESNE, CJ WINSKY, L MONIOT, B RAYMOND, J TI LOCALIZATION OF CALRETININ MESSENGER-RNA IN RAT AND GUINEA-PIG INNER-EAR BY IN-SITU HYBRIDIZATION USING RADIOACTIVE AND NONRADIOACTIVE PROBES SO HEARING RESEARCH LA English DT Article DE CALRETININ; COCHLEA; VESTIBULE; IN-SITU HYBRIDIZATION; OLIGONUCLEOTIDE PROBE; DIGOXIGENIN; RAT; GUINEA PIG ID CALCIUM-BINDING PROTEIN; ALZHEIMER-TYPE DEMENTIA; CALBINDIN-D 28K; PARVALBUMIN IMMUNOCYTOCHEMISTRY; VESTIBULAR GANGLION; NERVOUS-SYSTEM; NEURONS; HIPPOCAMPUS; IMMUNOREACTIVITY; IDENTIFICATION AB The localization of calretinin mRNA was studied in the rat and guinea pig inner ear by in situ hybridization, and compared to the distribution of the protein previously examined by immunocytochemistry. Radioactive and non-radioactive in situ hybridizations (ISH) were performed using oligonucleotide probes labelled with S-35 or digoxigenin. Radioactive ISH was more sensitive than non-radioactive ISH. In cochlear and vestibular ganglia, calretinin mRNA was localized in subpopulations of neurons with patterns of distribution similar to those shown by immunocytochemistry. By contrast, the observations in the sensory epithelia differed with the two techniques, ISH revealing less positive structures than immunocytochemistry. Rat inner hair cells and guinea pig inner hair cells, Hensen's cells and Deiters cells, which had been described strongly immunoreactive, appeared positive with radioactive but not with non-radioactive ISH. On the other hand, rat vestibular type II hair cells and guinea pig interdental cells of the spiral limbus which were faintly immunoreactive were not positive with both ISH techniques. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP DECHESNE, CJ (reprint author), INSERM,U254,LAB NEUROPHYSIOL SENSORIELLE LAB,UM2,CP 089,PL BATAILLON,F-34095 MONTPELLIER 5,FRANCE. NR 26 TC 28 Z9 28 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 SEP PY 1993 VL 69 IS 1-2 BP 91 EP 97 DI 10.1016/0378-5955(93)90096-J PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA LW840 UT WOS:A1993LW84000010 PM 8226353 ER PT J AU AKATSUKA, T DONETS, M SCAGLIONE, L CHING, WM SHIH, JWK DIBISCEGLIE, AM FEINSTONE, SM AF AKATSUKA, T DONETS, M SCAGLIONE, L CHING, WM SHIH, JWK DIBISCEGLIE, AM FEINSTONE, SM TI B-CELL EPITOPES ON THE HEPATITIS-C VIRUS NUCLEOCAPSID PROTEIN DETERMINED BY HUMAN MONOSPECIFIC ANTIBODIES SO HEPATOLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; EPSTEIN-BARR VIRUS; CHRONIC NON-A; AMINO-ACID; ANTIGENIC DETERMINANTS; PEPTIDE-SYNTHESIS; GENOME; IDENTIFICATION; ORGANIZATION; ENVELOPE AB Four monospecific antibodies against the hepatitis C virus nucleocapsid protein, which was expressed by recombinant baculovirus, were obtained by Epstein-Barr virus transformation of B cells from three patients with chronic hepatitis C virus infection. One of these antibodies was IgG and the other three were IgM. Their specificities were characterized initially by enzyme-linked immunosorbent assay and immunoblotting against hepatitis C virus proteins expressed by six recombinant baculoviruses with different hepatitis C virus sequence insertions. These specificities were confirmed, and their epitopes were more precisely determined with a series of overlapping decapeptides made by solid-phase pin technology. Two antibodies (1F4 and 2G6) reacted with the same peptides located near the amino(N)-terminus of nucleocapsid protein (amino acids 33-50). The third antibody (3B5) recognized the peptide consisting of amino acids 133-142, and the fourth antibody (3B9) was mapped to the carboxy(C)-terminus and reacted with a peptide consisting of amino acids 165-174. This epitope has not previously been reported. Two antibodies, 1F4 and 3B9, which are specific to the N-terminus and C-terminus of nucleocapsid protein, respectively, have been stably produced for more than 6 mo and are being subcloned to establish monoclonality. These antibodies should be useful reagents for the study of hepatitis C virus. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BLDG 29A,ROOM 1D14,BETHESDA,MD 20892. NIDDKD,DEPT TRANSFUS MED CLIN MED,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20814. NR 33 TC 23 Z9 23 U1 0 U2 3 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 SEP PY 1993 VL 18 IS 3 BP 503 EP 510 DI 10.1016/0270-9139(93)90348-Q PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV018 UT WOS:A1993LV01800005 PM 7689529 ER PT J AU SWAIN, MG VERGALLA, J JONES, EA AF SWAIN, MG VERGALLA, J JONES, EA TI PLASMA ENDOPEPTIDASE-24.11 (ENKEPHALINASE) ACTIVITY IS MARKEDLY INCREASED IN CHOLESTATIC LIVER-DISEASE SO HEPATOLOGY LA English DT Article ID ATRIAL-NATRIURETIC-PEPTIDE; PRIMARY BILIARY-CIRRHOSIS; NEUTRAL ENDOPEPTIDASE; KIDNEY; METALLOENDOPEPTIDASE; PURIFICATION; METABOLISM; HYDROLYSIS; ENDOTHELIN AB Endopeptidase 24.11 (enkephalinase), an enzyme known to be present in plasma and liver, is capable of metabolizing a substantial number of bioactive peptides. We measured plasma endopeptidase 24.11 activity in normal subjects and in patients with chronic hepatocellular disease or chronic cholestatic liver disease. The mean level of plasma endopeptidase 24.11 activity was 13 times higher in cholestatic patients than in controls or patients with hepatocellular disease (p < 0.01). Plasma endopeptidase 24.11 activity in patients correlated closely with traditional serum markers of cholestasis, including levels of alkaline phosphatase, gamma-glutamyltranspeptidase and aminopeptidase (p < 0.01 for all). However, plasma endopeptidase 24.11 activity correlated poorly with serum ALT aminotransferase level (p = NS), indicating that it is not a marker of hepatocellular disease. The lack of overlap between plasma endopeptidase 24.11 activity in cholestatic patients and noncholestatic liver disease controls suggests that this enzyme activity is a useful biochemical marker of cholestasis. In addition, because of the broad spectrum of peptides metabolized by endopeptidase 24.11, increased plasma endopeptidase 24.11 activity may contribute to the pathophysiology of the syndrome of cholestasis. C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NR 20 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1993 VL 18 IS 3 BP 556 EP 558 DI 10.1016/0270-9139(93)90354-P PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV018 UT WOS:A1993LV01800011 PM 8103033 ER PT J AU GORDEN, P CYPHERS, DF FELD, C AF GORDEN, P CYPHERS, DF FELD, C TI BUDGET TRENDS AND ISSUES AFFECTING BIOMEDICAL-RESEARCH - A PERSPECTIVE FROM THE NATIONAL-INSTITUTE-OF-DIABETES-AND-DIGESTIVE-AND-KIDNEY-DISEASES SO HEPATOLOGY LA English DT Article RP GORDEN, P (reprint author), NIDDKD,BLDG 31,ROOM 9A52,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1993 VL 18 IS 3 BP 677 EP 687 DI 10.1016/0270-9139(93)90370-3 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV018 UT WOS:A1993LV01800027 PM 8359808 ER PT J AU PU, YM YEH, H ZIFFER, H AF PU, YM YEH, H ZIFFER, H TI AN UNUSUAL ACID-CATALYZED REARRANGEMENT OF 1,2,4-TRIOXANES SO HETEROCYCLES LA English DT Article ID QINGHAOSU ARTEMISININ; DERIVATIVES AB A new Lewis acid-catalyzed rearrangement of the peroxide group in two 1,2,4-trioxanes, deoxoartemisinin and 12beta-allyldeoxoartemisinin, yielding ring enlarged oxide, is described. RP PU, YM (reprint author), NIH,BLDG 5,ROOM B1-31,BETHESDA,MD 20892, USA. NR 16 TC 15 Z9 15 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD SEP 1 PY 1993 VL 36 IS 9 BP 2099 EP 2107 PG 9 WC Chemistry, Organic SC Chemistry GA LW257 UT WOS:A1993LW25700021 ER PT J AU CHAN, KC LEWIS, KC PHANG, JM ISSAQ, HJ AF CHAN, KC LEWIS, KC PHANG, JM ISSAQ, HJ TI SEPARATION OF RETINOIC ACID ISOMERS USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Note DE RETINOIC ACIDS; MICELLAR ELECTROKINETIC CHROMATOGRAPHY ID PLASMA C1 NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21702. RP CHAN, KC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,PROGRAM RESOURCES,FREDERICK,MD 21702, USA. NR 11 TC 3 Z9 4 U1 0 U2 0 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD SEP PY 1993 VL 16 IS 9 BP 560 EP 561 PG 2 WC Chemistry, Analytical SC Chemistry GA MK703 UT WOS:A1993MK70300011 ER PT J AU ABRAHAM, LJ MARLEY, JV NEDOSPASOV, SA CAMBONTHOMSEN, A CROUAUROY, B DAWKINS, RL GIPHART, MJ AF ABRAHAM, LJ MARLEY, JV NEDOSPASOV, SA CAMBONTHOMSEN, A CROUAUROY, B DAWKINS, RL GIPHART, MJ TI MICROSATELLITE, RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM, AND SEQUENCE-SPECIFIC OLIGONUCLEOTIDE TYPING OF THE TUMOR-NECROSIS-FACTOR REGION - COMPARISONS OF THE 4AOHW CELL PANEL SO HUMAN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 4th Asia-Oceania Histocompatibility Workshop (AOHW): International Cooperation in the Asian-Panoceanian Region CY APR 22-29, 1993 CL PERTH, AUSTRALIA ID FACTOR TNF LOCUS; ANCESTRAL HAPLOTYPES; BETA GENE AB The location of the TNF and other genes in the central MHC and their possible relevance to disease susceptibility provided an impetus to develop useful typing markers. The 4AOHW undertook to assess the various markers available, including DNA sequence-based systems. A panel of well-characterized lymphoblastoid cell lines were typed by Nco I RLFP analysis, SSO typing, and TNF microsatellite typing. RFLP and SSO typing were relatively reproducible as judged by the blind replicates. The two techniques provided the same results with only one exception, and it would be reasonable to prefer SSO typing because of its advantages in terms of cost and time. Microsatellite typing was much more discriminating but, as expected, less robust in chat some discrepancies were apparent. As a result of the workshop and subsequent testing, alleles and haplotypes were allocated to most cells within the 4AOHW panel, including IOW cells typed in previous studies. While there was evidence that microsatellites may be relatively stable, they have the potential to identify recent mutations within ancestral haplotypes. C1 ROYAL PERTH HOSP,INST MOLEC GENET & IMMUNOL,DEPT CLIN IMMUNOL,PERTH,WA 6001,AUSTRALIA. SIR CHARLES GAIRDNER HOSP,DEPT CLIN IMMUNOL,PERTH,WA,AUSTRALIA. ENGELHARDT INST MOLEC BIOL,CYTOKINE RES UNIT,MOSCOW,RUSSIA. NCI,FCRDC,BRMP,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. CNRS,CTR RES GENET POLYMORPHISM HUMAN POPULAT,TOULOUSE,FRANCE. UNIV HOSP LEIDEN,DEPT IMMUNOHEMATOL & BLOOD BANK,LEIDEN,NETHERLANDS. UNIV WESTERN AUSTRALIA,DEPT CLIN IMMUNOL,PERTH,WA,AUSTRALIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Marley, Julia/A-9515-2009; Nedospasov, Sergei/Q-7319-2016 OI Marley, Julia/0000-0003-1014-4860; NR 11 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP PY 1993 VL 38 IS 1 BP 17 EP 23 DI 10.1016/0198-8859(93)90515-3 PG 7 WC Immunology SC Immunology GA MN660 UT WOS:A1993MN66000003 PM 7905869 ER PT J AU CARRERA, P CORDERA, R FERRARI, M CREMONESI, L TARAMELLI, R ANDRAGHETTI, G CARDUCCI, C DOZIO, N POZZA, G TAYLOR, SI MICOSSI, P BARBETTI, F AF CARRERA, P CORDERA, R FERRARI, M CREMONESI, L TARAMELLI, R ANDRAGHETTI, G CARDUCCI, C DOZIO, N POZZA, G TAYLOR, SI MICOSSI, P BARBETTI, F TI SUBSTITUTION OF LEU FOR PRO-193 IN THE INSULIN-RECEPTOR IN A PATIENT WITH A GENETIC FORM OF SEVERE INSULIN-RESISTANCE SO HUMAN MOLECULAR GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; GROWTH FACTOR-I; EXTRACELLULAR DOMAIN; CELL-SURFACE; ACANTHOSIS NIGRICANS; IMPAIRS TRANSPORT; ALPHA-SUBUNIT; BETA-SUBUNIT; MUTATION AB Mutations have been identified in the insulin receptor (IR) gene in patients who are insensitive to insulin action. We studied an extremely insulin resistant patient whose insulin binding to Epstein - Barr virus (EBV) transformed lymphocytes was severely reduced. Transmembrane signalling, evaluated as insulin receptor autophosphorylation, was normal. The patient's IR was immunoprecipitated normally by AbP6, a polyclonal antibody directed to the beta subunit. However, there was an almost-equal-to 50% decrease in the affinity of IR immunoprecipitation by a monoclonal antibody (MA-10) directed against the alpha subunit. These observations suggested that there was likely to be a mutation in the patient's insulin receptor that caused misfolding of the IR alpha subunit. Analysis of gene structure by Southern blotting experiments did not reveal any major deletion in the IR gene of the proband. Northern blot analysis showed a normal level of expression of IR gene. We applied denaturing gradient gel electrophoresis (DGGE) as well as direct sequence analysis to study the 22 exons of IR gene amplified by polymerase chain reaction (PCR) using the proband's genomic DNA as a template. We identified a new missense mutation substituting leucine (CTG) for proline (CCG) in homozygous state at codon 193 in exon 3. Both parents are heterozygous for the Leu193 mutation. The Leu193 mutation was not detected in any of 75 normal subjects (150 chromosomes), indicating that it is not a common sequence variant of the insulin receptor. In addition, during the course of screening the patient's DNA with perpendicular DGGE, we identified two previously unreported silent substitutions in exon 9. We conclude that Leu193 mutation is likely to be responsible for causing the patient's disease. C1 IRCCS HS RAFFAELE,DEPT LAB MED,I-20132 MILAN,ITALY. IRCCS HS RAFFAELE,DIBIT,I-20132 MILAN,ITALY. IRCCS HS RAFFAELE,DEPT INTERNAL MED,I-20132 MILAN,ITALY. UNIV GENOA,DISEM,I-16100 GENOA,ITALY. UNIV MILAN,DEPT BIOL & GENET MICROORGANISMS,I-20100 MILAN,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00161 ROME,ITALY. NIDDK,DIABET BRANCH,BETHESDA,MD 20892. HS RAFFAELE,I-00100 ROME,ITALY. RI Carrera, Paola/I-4105-2012 NR 31 TC 11 Z9 12 U1 0 U2 2 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 SEP PY 1993 VL 2 IS 9 BP 1437 EP 1441 DI 10.1093/hmg/2.9.1437 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LX497 UT WOS:A1993LX49700015 PM 8242067 ER PT J AU GEORGE, MS TRIMBLE, MR ROBERTSON, MM AF GEORGE, MS TRIMBLE, MR ROBERTSON, MM TI FLUVOXAMINE AND SULPIRIDE IN COMORBID OBSESSIVE-COMPULSIVE DISORDER AND GILLES-DE-LA-TOURETTE SYNDROME SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE OCD; OBSESSIVE-COMPULSIVE; TOURETTE SYNDROME; DOPAMINE; SEROTONIN; FLUVOXAMINE; SULPIRIDE ID FLUOXETINE TREATMENT; DOPAMINE; RECEPTORS; CLOMIPRAMINE; HALOPERIDOL; PIMOZIDE; RELEASE; SCALE AB Recently interest has arisen concerning the genetic, pharmacologic and phenomenologic links between Gilles de la Tourette Syndrome (GTS) and Obsessive-Compulsive Disorder (OCD). Some theorize the two disorders may be phenotypic variations of the same neurobiologic defect. Previous studies have demonstrated serotonin (5HT) abnormalities in OCD patients and dopamine dysfunction in patients with tics and GTS. We probed the relationship between 5HT and dopamine in these disorders with a 14-week, double-blind, placebo-controlled crossover trial of fluvoxamine (a specific 5HT reuptake inhibitor) versus sulpiride (a dopamine (D2) antagonist) followed by single-blind combined therapy (4 weeks) in 11 subjects with comorbid OCD and GTS. Sulpiride monotherapy significantly reduced tics and non-significantly improved OC symptoms. Fluvoxamine, either alone or combined with sulpiride, non-significantly ameliorated tics and reduced OCD symptoms. Additionally, tics and OC symptoms covaried. These results are consistent with a possible coupling of dopaminergic and 5HT systems in comorbid OCD/GTS subjects. C1 UCMSM,MIDDLESEX HOSP,ACAD DEPT PSYCHIAT,LONDON,ENGLAND. INST NEUROL,LONDON WC1N 3BG,ENGLAND. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE RD,BETHESDA,MD 20892, USA. NR 47 TC 30 Z9 30 U1 6 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD SEP-OCT PY 1993 VL 8 IS 5 BP 327 EP 334 DI 10.1002/hup.470080505 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA MT244 UT WOS:A1993MT24400004 ER PT J AU BURSON, JM LANG, JA GROSS, KW AGUILERA, G SIGMUND, CD AF BURSON, JM LANG, JA GROSS, KW AGUILERA, G SIGMUND, CD TI DIFFERENTIAL EXPRESSION AND REGULATION OF THE ANGIOTENSIN TYPE-1 (AT-1) RECEPTOR MESSENGER-RNA IN THE MOUSE SO HYPERTENSION LA English DT Meeting Abstract C1 ROSWELL PK CANC INST,BUFFALO,NY. NICHHD,BETHESDA,MD. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1993 VL 22 IS 3 BP 422 EP 422 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LW313 UT WOS:A1993LW31300093 ER PT J AU PARMER, RJ XI, XP WU, HJ HELMAN, LJ PETZ, LN AF PARMER, RJ XI, XP WU, HJ HELMAN, LJ PETZ, LN TI CHROMOGRANIN-A (CGA) CONTAINS A DOMINANT TARGETING SIGNAL FOR THE REGULATED SECRETORY PATHWAY IN RAT PHEOCHROMOCYTOMA CELLS SO HYPERTENSION LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. VET ADM MED CTR,SAN DIEGO,CA 92161. NCI,BETHESDA,MD 20892. 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1993 VL 22 IS 3 BP 422 EP 422 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LW313 UT WOS:A1993LW31300096 ER PT J AU DURG, A STOECKER, WV COOKSON, JP UMBAUGH, SE MOSS, RH AF DURG, A STOECKER, WV COOKSON, JP UMBAUGH, SE MOSS, RH TI IDENTIFICATION OF VARIEGATED COLORING IN SKIN TUMORS - NEURAL-NETWORK VS RULE-BASED INDUCTION METHODS SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article C1 UNIV MISSOURI,DEPT INTERNAL MED,COLUMBIA,MO 65201. UNIV MISSOURI,DEPT COMP SCI,COLUMBIA,MO 65201. STOECKER & ASSOCIATES,ROLLA,MO 65401. NATL LIB MED,BETHESDA,MD. SO ILLINOIS UNIV,DEPT ELECT ENGN,CARBONDALE,IL 62901. RP DURG, A (reprint author), UNIV MISSOURI,DEPT ELECT ENGN,ROLLA,MO 65401, USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP PY 1993 VL 12 IS 3 BP 71 EP & DI 10.1109/51.232345 PG 0 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA LX094 UT WOS:A1993LX09400013 ER PT J AU TRAYANOVA, NA ROTH, BJ MALDEN, LJ AF TRAYANOVA, NA ROTH, BJ MALDEN, LJ TI THE RESPONSE OF A SPHERICAL HEART TO A UNIFORM ELECTRIC-FIELD - A BIDOMAIN ANALYSIS OF CARDIAC STIMULATION SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID ASYMPTOTIC ANALYSIS; TRABECULAR MUSCLE; MAMMALIAN HEART; MODEL; PROPAGATION; MECHANISM; BUNDLE; TISSUE; POINT AB A mathematical model describing electrical stimulation of the heart is developed, in which a uniform electric field is applied to a spherical shell of cardiac tissue. The electrical properties of the tissue are characterized using the bidomain model. Analytical expressions for the induced transmembrane potential are derived for the cases of equal anisotropy ratios in the intracellular and interstitial (extracellular) spaces, and no transverse coupling between fibers. Numerical calculations of the transmembrane potential are also performed using realistic electrical conductivities. The model illustrates several mechanisms for polarization of the cell membrane, which can be divided into two categories, depending on if they polarize fibers at the heart surface only or if they polarize fibers both at the surface and within the bulk of the tissue. The latter mechanisms can be classified further according to whether they originate from continuous or discrete properties of cardiac tissue. If cardiac tissue had equal anisotropy ratios, a large membrane polarization would be induced at the heart surface that would become negligible a few length constants into the tissue. If cardiac tissue were continuous and had no transverse coupling between fibers, a membrane polarization would be induced throughout the bulk that would arise from an ''activating function'' similar to the one used to describe neural stimulation. Polarization would occur if the fibers were curving, if the cross-sectional area of the tissue were changing (fiber branching), or both. The numerically calculated transmembrane potential is intermediate between those predicted using the assumptions of equal anisotropy ratios and no transverse coupling between fibers. Although discrete properties of cardiac tissue are not incorporated into this model, an estimate of their effect indicates that the amplitude of the polarization caused by the resistance of the cellular junctions is similar to that caused by fiber curvature and branching. The spatial distribution of the polarization, however, is quite different. C1 DUKE UNIV,DEPT BIOMED ENGN,DURHAM,NC 27708. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP TRAYANOVA, NA (reprint author), NATL SCI FDN,ENGN RES CTR,DURHAM,NC 27708, USA. RI Roth, Bradley/A-4920-2008; Trayanova, Natalia/A-3386-2010 NR 24 TC 86 Z9 86 U1 0 U2 3 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 SEP PY 1993 VL 40 IS 9 BP 899 EP 908 DI 10.1109/10.245611 PG 10 WC Engineering, Biomedical SC Engineering GA MH972 UT WOS:A1993MH97200007 PM 8288281 ER PT J AU CARRINGTON, M YEAGER, M MANN, D AF CARRINGTON, M YEAGER, M MANN, D TI CHARACTERIZATION OF HLA-DMB POLYMORPHISM SO IMMUNOGENETICS LA English DT Note ID CLASS-II REGION; GENES; LOCUS; DNA; SB C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP CARRINGTON, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 13 TC 58 Z9 59 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 1993 VL 38 IS 6 BP 446 EP 449 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA LY715 UT WOS:A1993LY71500009 PM 8406617 ER PT J AU SADZIENE, A BARBOUR, AG ROSA, PA THOMAS, DD AF SADZIENE, A BARBOUR, AG ROSA, PA THOMAS, DD TI AN OSPB MUTANT OF BORRELIA-BURGDORFERI HAS REDUCED INVASIVENESS IN-VITRO AND REDUCED INFECTIVITY IN-VIVO SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; SURFACE PROTEIN-A; IMMUNODEFICIENCY SCID MOUSE; ESCHERICHIA-COLI; ANTIGENIC DETERMINANT; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEINS; LABORATORY MICE; LINEAR-PLASMID; CULTIVATION AB Most Borrelia burgdorferi strains have two major surface proteins, OspA and OspB. In the present study, we selected from a clonal population of infectious B. burgdorferi an OspB escape mutant, identified the genetic basis for this phenotype, and evaluated its functional activities. Selection with the anti-OspB antibody H614 was performed in vitro in medium and extended in vivo in scid mice. Mutants with a truncated OspB protein were selected at a frequency of 1 x 10(-5) to 3 x 10(-5). After no major rearrangements in DNA were detected, sequence analysis of the mutant's ospAB locus revealed a single base change in the consensus ribosomal binding sequence for ospB and a single nucleotide deletion in the ospB gene itself. The effect of these mutations was reduced expression of a truncated OspB protein. When functional abilities of the wild type and mutant were compared, the mutant had a threefold-lower capacity to penetrate a human endothelium umbilical vein cell monolayer. Infectivity of wild-type and mutant cells for scid mice was evaluated by culturing different organs, and the median infectious dose was calculated. The inoculum of mutant cells for infecting the mice was 30- to 300-fold higher than that of wild-type cells. This study shows that reduced size and expression of OspB are associated with lowered virulence of B. burgdorferi. Selection of mutants that to some degree remain infectious is one approach to defining the role of different surface proteins in the pathogenesis of Lyme disease. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PERIODONT,SAN ANTONIO,TX 78284. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NIAID NIH HHS [AI-26804, AI-29731] NR 51 TC 87 Z9 87 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 SEP PY 1993 VL 61 IS 9 BP 3590 EP 3596 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LU858 UT WOS:A1993LU85800002 PM 8359881 ER PT J AU TAMBOURGI, DV KIPNIS, TL DASILVA, WD JOINER, KA SHER, A HEATH, S HALL, BF OGDEN, GB AF TAMBOURGI, DV KIPNIS, TL DASILVA, WD JOINER, KA SHER, A HEATH, S HALL, BF OGDEN, GB TI A PARTIAL CDNA CLONE OF TRYPOMASTIGOTE DECAY-ACCELERATING FACTOR (T-DAF), A DEVELOPMENTALLY-REGULATED COMPLEMENT INHIBITOR OF TRYPANOSOMA-CRUZI, HAS GENETIC AND FUNCTIONAL SIMILARITIES TO THE HUMAN-COMPLEMENT INHIBITOR DAF SO INFECTION AND IMMUNITY LA English DT Article ID 85-KD SURFACE-ANTIGEN; HERPES-SIMPLEX VIRUS; MEMBRANE GLYCOPROTEIN; C-3 CONVERTASES; PROTEINS; BINDING; PATHWAY; FAMILY; FORMS; PURIFICATION AB Resistance to complement-mediated lysis in Trypanosoma cruzi is due to the expression of complement-regulatory factors by the virulent developmental forms of this protozoan parasite. An 87- to 93-kDa molecule, which we have termed T-DAF (trypomastigote decay-accelerating factor), is present on the surface of the parasite and inhibits complement activation in a manner functionally similar to the mammalian complement regulatory component, decay-accelerating factor. In this report, we characterized monospecific polyclonal and monoclonal antibodies which were obtained from mice and rabbits immunized with fast protein liquid chromatography-purified T-DAF. These polyclonal antibodies were shown to inhibit T-DAF activity and were capable of inducing lysis of the parasites. Both the polyclonal and monoclonal antibodies were used to screen a cDNA expression library prepared from T. cruzi trypomastigote mRNA. From this library, we obtained a partial lambdagt11 cDNA clone which showed genetic and functional similarity to the human C3 convertase inhibitor DAF (A. Nicholson-Weller, J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen, J. Immunol. 129:184-189, 1982). C1 YALE UNIV,DEPT INTERNAL MED,INFECT DIS SECT,NEW HAVEN,CT 06510. INST BUTANTAN,IMUNOQUIM LAB,SAO PAULO,BRAZIL. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP TAMBOURGI, DV (reprint author), UNIV SAO PAULO,INST CIENCIAS BIOMED,DEPT IMUNOL,IMUNOL PARASITOSES LAB,SAO PAULO,BRAZIL. NR 42 TC 34 Z9 35 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 SEP PY 1993 VL 61 IS 9 BP 3656 EP 3663 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LU858 UT WOS:A1993LU85800011 PM 7689538 ER PT J AU TAYLOR, DN TROFA, AC SADOFF, J CHU, CY BRYLA, D SHILOACH, J COHEN, D ASHKENAZI, S LERMAN, Y EGAN, W SCHNEERSON, R ROBBINS, JB AF TAYLOR, DN TROFA, AC SADOFF, J CHU, CY BRYLA, D SHILOACH, J COHEN, D ASHKENAZI, S LERMAN, Y EGAN, W SCHNEERSON, R ROBBINS, JB TI SYNTHESIS, CHARACTERIZATION, AND CLINICAL-EVALUATION OF CONJUGATE VACCINES COMPOSED OF THE O-SPECIFIC POLYSACCHARIDES OF SHIGELLA-DYSENTERIAE TYPE-1, SHIGELLA-FLEXNERI TYPE-2A, AND SHIGELLA-SONNEI (PLESIOMONAS-SHIGELLOIDES) BOUND TO BACTERIAL TOXOIDS SO INFECTION AND IMMUNITY LA English DT Article ID SERUM ANTIBODIES; ESCHERICHIA-COLI; NATURAL IMMUNITY; LIPOPOLYSACCHARIDE; PROTECTION; IMMUNIZATION; ANTIGEN; INFECTIONS; VIRULENCE; CHILDREN AB The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 mug of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 mug of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. ISRAEL DEF FORCES,MED CORPS,TEL AVIV,ISRAEL. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NIDDKD,CELLULAR & MOLEC BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. RP TAYLOR, DN (reprint author), WALTER REED ARMY INST RES,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307, USA. NR 52 TC 109 Z9 115 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 SEP PY 1993 VL 61 IS 9 BP 3678 EP 3687 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LU858 UT WOS:A1993LU85800014 PM 8359890 ER PT J AU PINCUS, SH COLE, RL KAMANGASOLLO, E FISCHER, SH AF PINCUS, SH COLE, RL KAMANGASOLLO, E FISCHER, SH TI INTERACTION OF GROUP-B STREPTOCOCCAL OPACITY VARIANTS WITH THE HOST-DEFENSE SYSTEM SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE; CAPSULE AB Group B streptococci (GBS) demonstrate high-frequency phase variation of colony opacity. Colony opacity is a function of chain length, with opaque colonies consisting of GBS that form longer chains. Because opaque variants do not grow on standard streptococcal media, the role of opacity variation in GBS infection has not been studied. We have isolated stable variants from type III GBS that are either transparent (variants 1.2 and 1.3) or opaque (variants 1.1 and 1.5). In this study, we evaluated the interactions of these variants with different components of the host immune system both in vitro and in vivo. Opaque GBS were less immunogenic than transparent GBS. Opaque GBS were more susceptible to killing by polymorphonuclear neutrophils (PMNs) and could induce a chemiluminescent response of PMNs in the absence of antibody (Ab) or complement. Transparent GBS did not induce neutrophil chemiluminescence in the absence of Ab and complement. However, in the presence of Ab and complement, transparent GBS induced a stronger chemiluminescent response than did opaque GBS. Scanning electron micrographs of PMNs and GBS demonstrated differences in the attachment and engulfment of the different variants by the PMNs as well as different effects of the GBS on the PMNs themselves. Interactions with complement were affected by GBS opacity as well, with opaque variant 1.1 initiating complement activation in the absence of any Ab. The virulence of the GBS opacity variants was studied in vivo by inoculation of graded numbers of GBS into newborn mice. Transparent variants 1.2 and 1.3 were most virulent, with variant 1.1 intermediate and variant 1.5 minimally virulent. However, in mixed infections, variant 1.5 greatly enhanced the virulence of small numbers of transparent GBS. These results indicate that the opacity status of GBS can influence the interaction between the GBS and the host immune system. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 9 TC 11 Z9 11 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 SEP PY 1993 VL 61 IS 9 BP 3761 EP 3768 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LU858 UT WOS:A1993LU85800025 PM 8359897 ER PT J AU OTTESEN, EA AF OTTESEN, EA TI FILARIAL INFECTIONS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID TROPICAL PULMONARY EOSINOPHILIA; LYMPHATIC FILARIASIS; HYPERRESPONSIVE SYNDROME; BANCROFTIAN FILARIASIS; DIETHYLCARBAMAZINE; LOIASIS; ANTIBODY; IGG4; IVERMECTIN; DISEASE RP OTTESEN, EA (reprint author), NIAID,PARASIT DIS LAB,CLIN PARASITOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 34 TC 24 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1993 VL 7 IS 3 BP 619 EP 633 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LY445 UT WOS:A1993LY44500010 PM 8254163 ER PT J AU LUCEY, DR MAGUIRE, JH AF LUCEY, DR MAGUIRE, JH TI SCHISTOSOMIASIS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID CIRCULATING ANODIC ANTIGEN; MANSONI INFECTION; HEPATIC SCHISTOSOMIASIS; PERIPORTAL FIBROSIS; KATAYAMA FEVER; VIRUS TYPE-1; SPINAL-CORD; HLA-DR; PRAZIQUANTEL; HAEMATOBIUM C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV INFECT DIS,BOSTON,MA 02115. RP LUCEY, DR (reprint author), NCI,EXPTL IMMUNOL BRANCH,ROOM 4B-17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 119 TC 27 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1993 VL 7 IS 3 BP 635 EP 653 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LY445 UT WOS:A1993LY44500011 PM 8254164 ER PT J AU COHEN, OJ KEISER, J POLLNER, J PARENTI, DM AF COHEN, OJ KEISER, J POLLNER, J PARENTI, DM TI PROSTHETIC JOINT INFECTION WITH ACTINOMYCES-VISCOSUS SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Note C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DIV INFECT DIS,WASHINGTON,DC 20037. RP COHEN, OJ (reprint author), NIAID,9000 ROCKVILLE PIKE,10-11B13,BETHESDA,MD 20892, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD SEP-OCT PY 1993 VL 2 IS 5 BP 349 EP 351 DI 10.1097/00019048-199309000-00007 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MF197 UT WOS:A1993MF19700008 ER PT J AU LINNOILA, M VIRKKUNEN, M GEORGE, T HIGLEY, D AF LINNOILA, M VIRKKUNEN, M GEORGE, T HIGLEY, D TI IMPULSE CONTROL DISORDERS SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL SCIENTIFIC SYMP ON DEPRESSION - OBSESSIVE-COMPULSIVE DISORDER ( OCD ) - ANXIETY CY MAY 08, 1993 CL MAINZ, GERMANY SP DUPHAR MED COMMUN, SOLVAY GRP, UPJOHN GERMANY ID CEREBROSPINAL-FLUID; VIOLENT OFFENDERS; FIRE SETTERS; MONOAMINE METABOLITES; AMINE METABOLITES; SEROTONIN; CSF; ALCOHOLICS; BEHAVIOR; SUICIDE C1 UNIV HELSINKI,DEPT PSYCHIAT,SF-00100 HELSINKI 10,FINLAND. RP LINNOILA, M (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BLDG 10,ROOM 3C103,BETHESDA,MD 20892, USA. NR 28 TC 49 Z9 49 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 1993 VL 8 SU 1 BP 53 EP 56 DI 10.1097/00004850-199309001-00008 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA MB051 UT WOS:A1993MB05100008 PM 7504705 ER PT J AU TAKESHITA, T KOZLOWSKI, S ENGLAND, RD BROWER, R SCHNECK, J TAKAHASHI, H DELISI, C MARGULIES, DH BERZOFSKY, JA AF TAKESHITA, T KOZLOWSKI, S ENGLAND, RD BROWER, R SCHNECK, J TAKAHASHI, H DELISI, C MARGULIES, DH BERZOFSKY, JA TI ROLE OF CONSERVED REGIONS OF CLASS-I MHC MOLECULES IN THE ACTIVATION OF CD8+ CYTOTOXIC T-LYMPHOCYTES BY PEPTIDE AND PURIFIED CELL-FREE CLASS-I MOLECULES SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD8+; CONSERVED REGIONS; CYTOTOXIC T-LYMPHOCYTE; MHC ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALPHA-3 DOMAIN; ANTIGEN PRESENTATION; ENVELOPE PROTEIN; NEGATIVE SELECTION; PLANAR MEMBRANES; RECOGNITION; RECEPTOR; BINDING; INDUCTION AB To analyze the molecular interactions involved in CD8+ cytotoxic T lymphocyte (CTL) recognition quantitatively, we developed a cell-free antigen presenting system. Genetically engineered soluble H-2D(d) molecules coated on plastic microtiter plates could present HIV envelope peptide to an antigen-specific CTL clone, inducing it to produce IFN-gamma in the absence of accessory cells and their accessory or co-stimulatory molecules. The peptide - MHC complexes were functionally stable for over 24 h. The magnitude of T cell activation was dependent on the concentrations of both class I MHC molecule and the peptide, but was more sensitive to the concentration of the MHC molecule than to that of peptide. This result suggests that one MHC molecule can play more than one role in activating the CTL. One such role is the interaction between CD8 and a conserved region of class I MHC, as suggested by the finding that holding the total MHC concentration constant with an irrelevant class I MHC molecule (H-2K(b) engineered to have the same alpha3 domain as H-2D(d)) made the T cell response less sensitive to the change in concentration of the relevant MHC molecule (H-2D(d)). The irrelevant class I MHC molecule (H-2K(b)), unable to present this peptide by itself, augmented the T cell response at lower concentrations of peptide. These results suggest that the conserved a3 domain of the class I MHC heavy chain as well as polymorphic regions play an important role in T cell activation and that T cell interaction with MHC molecules not presenting peptide can still augment the response. C1 NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. BOSTON UNIV,COLL ENGN,DEPT ELECT SYST & COMP ENGN,BOSTON,MA 02215. BOSTON UNIV,COLL ENGN,DEPT BIOMED ENGN,BOSTON,MA 02215. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CLIN IMMUNOL & ALLERGY,BALTIMORE,MD 21224. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID NIH HHS [AI30535] NR 37 TC 15 Z9 15 U1 0 U2 0 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 SEP PY 1993 VL 5 IS 9 BP 1129 EP 1138 DI 10.1093/intimm/5.9.1129 PG 10 WC Immunology SC Immunology GA MA577 UT WOS:A1993MA57700015 PM 8241055 ER PT J AU NSAMENANG, AB LAMB, ME AF NSAMENANG, AB LAMB, ME TI THE ACQUISITION OF SOCIOCOGNITIVE COMPETENCE BY NSO CHILDREN IN THE BAMENDA GRASSFIELDS OF NORTHWEST CAMEROON SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article; Proceedings Paper CT WORKSHOP ON CONTINUITIES AND DISCONTINUITIES IN THE COGNITIVE SOCIALISATION OF MINORITY CHILDREN CY JUN, 1991 CL WASHINGTON, DC SP NIMH ID CULTURE AB Among the Nso of Northwest Cameroon, the primary purpose of socialisation is the development of social intelligence and a sense of social responsibility. This process is dependent on and shaped more by ''tacit lessions'' built into children's apprenticeship in routine tasks and interpersonal encounters with both peers and adults than on role instruction. Nso children are coparticipants in their own ''hands-on'' socialisation. The traditional niche is now in total flux. In order to compare the ideas and values of different parental cohorts inherent in the tension of continuity and change, we interviewed 389 Nso men and women using the Lamnso Parent Interview Guide. The results revealed both similarities and differences in the values of various parental cohorts. Although traditional values were widely endorsed, mothers, parents, and urban respondents tended to manifest less indigenous viewpoints than fathers, grandparents, and rural subjects, perhaps because of their greater exposure to alien modifiers of cultural knowledge and values. C1 NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20892. CAMEROON INST HUMAN SCI,BAMENDA,CAMEROON. NR 48 TC 14 Z9 15 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD SEP PY 1993 VL 16 IS 3 BP 429 EP 441 PG 13 WC Psychology, Developmental SC Psychology GA MA137 UT WOS:A1993MA13700004 ER PT J AU YOKOZAKI, H BUDILLON, A CLAIR, T KELLEY, K COWAN, KH ROHLFF, C GLAZER, RI CHOCHUNG, YS AF YOKOZAKI, H BUDILLON, A CLAIR, T KELLEY, K COWAN, KH ROHLFF, C GLAZER, RI CHOCHUNG, YS TI 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE AS A NOVEL MODULATOR OF MULTIDRUG-RESISTANCE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MULTIDRUG RESISTANCE; CYCLIC AMP; PROTEIN KINASE ID HL-60 LEUKEMIA-CELLS; CYCLIC-AMP ANALOGS; PROTEIN-KINASE-C; DRUG-RESISTANCE; P-GLYCOPROTEIN; GROWTH; LINES; EXPRESSION; DIFFERENTIATION; BREAST AB Multidrug resistance (MDR) is a major obstacle in the chemotherapy of cancer. 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP), a site-selective analog of cAMP, produced a potent growth inhibition in a spectrum of MDR cell lines. The IC50 (concentration inhibiting 50% of cell proliferation) of 8-Cl-cAMP at 6 days ranged from 0.1 to 3.0 muM in both P-glycoprotein (pgp)-associated and pgp-unassociated MDR cells, and the growth inhibition occurred with continued cell viability. Growth inhibition paralleled down-regulation of RIalpha subunit and catalytic activity of cAMP-dependent protein kinase. 8-Cl-cAMP also provoked the suppression of the promoter activity of the MDR1 gene. These results demonstrate that type I cAMP-dependent protein kinase plays a role in drug resistance and that 8-Cl-cAMP is a novel modulator of multidrug resistance. C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,RM 5B38,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC 20007. OI Budillon, Alfredo/0000-0002-6330-6053; Yokozaki, Hiroshi/0000-0001-5276-3331 NR 42 TC 24 Z9 24 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1993 VL 3 IS 3 BP 423 EP 430 PG 8 WC Oncology SC Oncology GA LQ902 UT WOS:A1993LQ90200002 PM 21573381 ER PT J AU DESMET, MD NUSSENBLATT, RB AF DESMET, MD NUSSENBLATT, RB TI CLINICAL USE OF CYCLOSPORINE IN OCULAR DISEASE SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP DESMET, MD (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N202,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 0 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1993 VL 33 IS 4 BP 31 EP 45 DI 10.1097/00004397-199303340-00005 PG 15 WC Ophthalmology SC Ophthalmology GA ME324 UT WOS:A1993ME32400003 PM 8258496 ER PT J AU KASNER, L CHAN, CC WHITCUP, SM GERY, I AF KASNER, L CHAN, CC WHITCUP, SM GERY, I TI THE PARADOXICAL EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN ENDOTOXIN-INDUCED UVEITIS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ENDOTOXIN-INDUCED UVEITIS; TUMOR NECROSIS FACTOR-ALPHA; INFLAMMATION; CYTOKINE; SEPTIC SHOCK ID TISSUE-INJURY; CACHECTIN; SHOCK; RATS; ANTIBODY; CHLORPROMAZINE; PERITONITIS; TOLERANCE; LETHALITY; ADHERENCE AB Purpose. To investigate the role of TNF-alpha in endotoxin-induced uveitis (EIU) in mice. Methods. To neutralize TNF-alpha activity, mice were pretreated with either repeated injections of this cytokine or a single injection of antibody against it. The mice were then injected intraperitoneally with 500 mug endotoxin, to induce lethal septic shock, or into the footpad with 200 mug to induce EIU. Results. Although both pretreatments conferred protection against the systemic toxic effects of LPS, TNF-resistant mice and mice treated with anti-TNF-alpha antibody demonstrated an exacerbation of EIU when compared to control animals. Conclusion. Unlike its apparent participation in the systemic effect of endotoxin, TNF-alpha is not directly involved in the pathogenesis of EIU and may even protect against the inflammatory processes of this disease. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N208,BETHESDA,MD 20892. NR 33 TC 84 Z9 85 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1993 VL 34 IS 10 BP 2911 EP 2917 PG 7 WC Ophthalmology SC Ophthalmology GA LW968 UT WOS:A1993LW96800012 PM 8360023 ER PT J AU URBA, WJ LONGO, DL AF URBA, WJ LONGO, DL TI HODGKINS-DISEASE IN ADULTS .2. SO INVESTIGATIVE RADIOLOGY LA English DT Review ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; 2ND MALIGNANT NEOPLASMS; TERM FOLLOW-UP; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; FIELD RADIATION-THERAPY; 1ST COMPLETE REMISSION; COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY RP URBA, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 122 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 1993 VL 28 IS 9 BP 848 EP 859 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LZ169 UT WOS:A1993LZ16900012 PM 8225893 ER PT J AU ELKES, J AF ELKES, J TI IN MEMORY OF HARMAN,ABRAHAM, 1914-1982 - BRAIN-FUNCTION IN HEALTH AND DISEASE SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Editorial Material C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NIMH,CLIN NEUROPHARMACOL RES CTR,BETHESDA,MD 20892. MCMASTER UNIV,HAMILTON L8S 4L8,ONTARIO,CANADA. UNIV LOUISVILLE,LOUISVILLE,KY 40292. RP ELKES, J (reprint author), NATL INST PSYCHOBIOL ISRAEL,JERUSALEM,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD SEP PY 1993 VL 29 IS 9 BP R2 EP R2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LY722 UT WOS:A1993LY72200002 ER PT J AU BROWN, MS COLLINS, FS GOLDSTEIN, JL WATSON, JD WEXLER, NS AF BROWN, MS COLLINS, FS GOLDSTEIN, JL WATSON, JD WEXLER, NS TI ROUND-TABLE - THE HUMAN GENOME PROJECT SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Discussion C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RP BROWN, MS (reprint author), UNIV TEXAS,SW MED CTR,DALLAS,TX 75230, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 1993 VL 10 IS 1 BP 43 EP 48 PG 6 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA MB290 UT WOS:A1993MB29000024 ER PT J AU BENINATI, W DERDAK, S DIXON, PF GRIDER, DJ STROLLO, DC HENSLEY, RE LUCEY, DR AF BENINATI, W DERDAK, S DIXON, PF GRIDER, DJ STROLLO, DC HENSLEY, RE LUCEY, DR TI PULMONARY EOSINOPHILS EXPRESS HLA-DR IN CHRONIC EOSINOPHILIC PNEUMONIA SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE PULMONARY EOSINOPHILIA; EOSINOPHILS; HLA-DR ANTIGEN; BRONCHOALVEOLAR LAVAGE FLUID; ASTHMA ID PERFUSED RAT LUNGS; MEDIATED INJURY; INFLAMMATION; FIBROSIS; INCREASE; ASTHMA; CELLS AB Background: Chronic eosinophilic pneumonia is a rare idiopathic disorder. What role the eosinophil plays in the pathogenesis of this disease is unknown. The recent finding that mature eosinophils can express the class II major histocompatibility complex molecule HLA-DR suggests an immunologic role, perhaps through antigen presentation. The purpose of this research was to determine whether lung-derived eosinophils exhibit in vivo expression of HLA-DR. Methods: Eosinophils were obtained simultaneously from bronchoalveolar lavage and peripheral blood from a 59-year-old woman with asthma and chronic eosinophilic pneumonia. Eosinophil-enriched aliquots of peripheral blood were cocultured with human lung fibroblasts (with or without additional granulocyte-macrophage colony-stimulating factor). The percentage of cells expressing HLA-DR was quantitated by flow cytometric analysis. Results: Eosinophils derived from bronchoalveolar lavage displayed in vivo expression of HLA-DR (86%) in contrast to those from peripheral blood (7%), suggesting compartmentalization of eosinophil activation within the lung. Peripheral blood eosinophils retained the capacity for HLA-DR expression when coincubated with lung fibroblasts (83%) with augmentation by granulocyte-macrophage colony-stimulating factor (93%). Conclusion: These data demonstrate that lung eosinophil HLA-DR expression occurs in vivo; it may contribute to the pathogenesis of inflammatory lung injury. C1 WILFORD HALL USAF MED CTR,DEPT PULM DIS,CLIN INVEST DIRECTORATE,SAN ANTONIO,TX. WILFORD HALL USAF MED CTR,DEPT PATHOL,SAN ANTONIO,TX. WILFORD HALL USAF MED CTR,DEPT RADIOL,SAN ANTONIO,TX. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 36 TC 34 Z9 34 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1993 VL 92 IS 3 BP 442 EP 449 DI 10.1016/0091-6749(93)90123-W PG 8 WC Allergy; Immunology SC Allergy; Immunology GA LX309 UT WOS:A1993LX30900010 PM 8360395 ER PT J AU KAULBACH, HC WHITE, MV IGARASHI, Y HAHN, BK KALINER, MA AF KAULBACH, HC WHITE, MV IGARASHI, Y HAHN, BK KALINER, MA TI ESTIMATION OF NASAL EPITHELIAL LINING FLUID USING UREA AS A MARKER SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE EPITHELIAL LINING FLUID; GLANDULAR SECRETION; VASCULAR PERMEABILITY; UREA ID BRONCHOALVEOLAR LAVAGE FLUID; PATHO-PHYSIOLOGY; ELECTROLYTE TRANSPORT; RHINITIS; SECRETIONS; LUNG; PERMEABILITY; ALLERGEN; PROTEIN; DISEASE AB Background: The luminal surface of respiratory mucous membranes is lined with an epithelial lining fluid (ELF) layer. Previous attempts to determine ELF volumes in airways have used dyes or freely diffusible molecules such as urea, yet have not led to a universally accepted method. The nasal mucous membrane provides an accessible area to examine whether urea is an appropriate marker of respiratory ELF volume. Methods and Results: Collection of undiluted nasal secretions after either glandular stimulation or induction of vascular permeability confirmed that plasma urea and nasal urea concentrations are equivalent. Baseline ELF volume was calculated as 800 mul/nostril. The calculated molar concentrations of urea in ELF did not vary with either methacholine or histamine challenge. Conclusions: These data indicate the plasma, interstitial, glandular and ELF urea concentrations are equivalent and, therefore, that urea is a useful marker of ELF volume in the nasal mucosa. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C205,BETHESDA,MD 20892. NR 35 TC 39 Z9 39 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1993 VL 92 IS 3 BP 457 EP 465 DI 10.1016/0091-6749(93)90125-Y PG 9 WC Allergy; Immunology SC Allergy; Immunology GA LX309 UT WOS:A1993LX30900012 PM 8360397 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI THE ANGELICAL CONJUNCTION - THE PREACHER-PHYSICIANS OF COLONIAL NEW-ENGLAND - WATSON,PA SO JOURNAL OF AMERICAN HISTORY LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION AMER HISTORIANS PI BLOOMINGTON PA 112 N BRYAN ST, BLOOMINGTON, IN 47408 SN 0021-8723 J9 J AM HIST JI J. Am. Hist. PD SEP PY 1993 VL 80 IS 2 BP 635 EP 636 DI 10.2307/2079890 PG 2 WC History SC History GA LV466 UT WOS:A1993LV46600026 ER PT J AU JENKINS, AJ MILLS, LC DARWIN, WD HUESTIS, MA CONE, EJ MITCHELL, JM AF JENKINS, AJ MILLS, LC DARWIN, WD HUESTIS, MA CONE, EJ MITCHELL, JM TI VALIDITY TESTING OF THE EZ-SCREEN(R) CANNABINOID TEST SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID METABOLITE C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. USN,DRUG SCREENING LAB,NAVAL AIR STN,JACKSONVILLE,FL 32212. NR 15 TC 11 Z9 11 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 1993 VL 17 IS 5 BP 292 EP 298 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA LU221 UT WOS:A1993LU22100007 PM 8107464 ER PT J AU HUESTIS, MA CONE, EJ AF HUESTIS, MA CONE, EJ TI CONCERNING BLOOD CANNABINOIDS AND THE EFFECT OF RESIDUAL THCCOOH ON CALCULATED EXPOSURE TIME - REPLY SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter ID DELTA-9-TETRAHYDROCANNABINOL THC; MARIJUANA; SMOKING RP HUESTIS, MA (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 1993 VL 17 IS 5 BP 314 EP 316 PG 3 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA LU221 UT WOS:A1993LU22100013 ER PT J AU ERZURUM, SC DANEL, C GILLISSEN, A CHU, CS TRAPNELL, BC CRYSTAL, RG AF ERZURUM, SC DANEL, C GILLISSEN, A CHU, CS TRAPNELL, BC CRYSTAL, RG TI IN-VIVO ANTIOXIDANT GENE-EXPRESSION IN HUMAN AIRWAY EPITHELIUM OF NORMAL INDIVIDUALS EXPOSED TO 100-PERCENT O-2 SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE SUPEROXIDE DISMUTASE; CATALASE; HYPEROXIA; MESSENGER RIBONUCLEIC ACID; QUANTIFICATION ID PULMONARY OXYGEN-TOXICITY; CONDUCTANCE REGULATOR GENE; CU,ZN SUPEROXIDE-DISMUTASE; XENOBIOTIC DETOXIFICATION; LUNG MITOCHONDRIA; OXIDATIVE STRESS; ENZYME-INDUCTION; CYSTIC-FIBROSIS; CDNA SEQUENCE; FREE-RADICALS AB Human bronchial epithelium is exquisitely sensitive to high O2 levels, with tracheobronchitis usually developing after 12 h of exposure to 100% O2. To evaluate whether this vulnerability results from inability of the bronchial epithelium to provide adequate antioxidant protection, we quantified antioxidant gene expression in bronchial epithelium of normal volunteers at baseline and after exposure to 100% O2 in vivo. After 14.8 +/- 0.2 h of 100% O2, 24 of 33 individuals had evidence of tracheobronchitis. Baseline gene expression of CuZn superoxide dismutase (SOD), MnSOD, and catalase in bronchial epithelium was very low (CuZnSOD 4.1 +/-0.8 transcripts/cell, MnSOD 5.1 +/- 0.9, catalase 1.3 +/- 0.2), with control gamma-actin expression relatively abundant (50 +/- 6 transcripts/cell). Importantly, despite 100% O2 exposure sufficient to cause tracheobronchitis in most individuals, antioxidant mRNA transcripts/cell in bronchial epithelium did not increase (P > 0.5). Catalase activity in bronchial epithelium did not change after exposure to hyperoxia (P > 0.05). Total SOD activity increased mildly (P < 0.01) but not sufficiently to protect the epithelium. Together, the very low levels of expression of intracellular antioxidant enzymes and the inability to upregulate expression at the mRNA level with oxidant stress likely have a role in human airway epithelium susceptibility to hyperoxia. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NR 38 TC 70 Z9 70 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1993 VL 75 IS 3 BP 1256 EP 1262 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LY896 UT WOS:A1993LY89600033 PM 8226538 ER PT J AU UCHIDA, I HORNUNG, JM THORNE, CB KLIMPEL, KR LEPPLA, SH AF UCHIDA, I HORNUNG, JM THORNE, CB KLIMPEL, KR LEPPLA, SH TI CLONING AND CHARACTERIZATION OF A GENE WHOSE PRODUCT IS A TRANSACTIVATOR OF ANTHRAX TOXIN SYNTHESIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEPENDENT ADENYLATE-CYCLASE; LETHAL FACTOR GENE; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; EDEMA FACTOR; MOLECULAR-CLONING; CAPSULE PLASMID; CARBON-DIOXIDE AB The 184-kb Bacillus anthracis plasmid pXO1, which is required for virulence, contains three genes encoding the protein components of anthrax toxin, cya (edema factor gene), lef (lethal factor gene), and pag (protective antigen gene). Expression of the three proteins is induced by bicarbonate or serum. Using a pag-lacZ transcriptional construct to measure pag promoter activity, we cloned in Bacillus subtilis a gene (atxA) whose product acts in trans to stimulate anthrax toxin expression. Deletion analysis located atxA on a 2.0-kb fragment between cya and pag. DNA sequencing identified one open reading frame encoding 476 amino acids with a predicted M(r) of 55,673, in good agreement with the value of 53 kDa obtained by in vitro transcription-translation analysis. The cloned atxA gene complemented previously characterized Tn917 insertion mutants UM23 tp29 and UM23 tp32 (J. M. Hornung and C. B. Thorne, Abstr. 91st Gen. Meet. Am. Soc. Microbiol. 1991, abstr. D-121, p. 98), which are deficient in synthesis of all three toxin proteins. These results demonstrate that the atxA product activates not only transcription of pag but also that of cya and lef. Beta-Galactosidase synthesis from the pag-lacZ transcriptional fusion construct introduced into an insertion mutant (UM23 tp62) which does not require bicarbonate for toxin synthesis indicated that additional regulatory genes other than atxA play a role in the induction of anthrax toxin gene expression by bicarbonate. C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. UNIV MASSACHUSETTS, DEPT MICROBIOL, AMHERST, MA 01003 USA. NR 44 TC 101 Z9 105 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1993 VL 175 IS 17 BP 5329 EP 5338 PG 10 WC Microbiology SC Microbiology GA LV387 UT WOS:A1993LV38700006 PM 8366021 ER PT J AU HO, C KULAEVA, OI LEVINE, AS WOODGATE, R AF HO, C KULAEVA, OI LEVINE, AS WOODGATE, R TI A RAPID METHOD FOR CLONING MUTAGENIC DNA-REPAIR GENES - ISOLATION OF UMU-COMPLEMENTING GENES FROM MULTIDRUG-RESISTANCE PLASMIDS R391, R446B, AND R471A SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEFICIENT ESCHERICHIA-COLI; RECA PROTEIN; SALMONELLA-TYPHIMURIUM; UV MUTAGENESIS; R-FACTORS; INCOMPATIBILITY GROUPS; INDUCIBLE MUTAGENESIS; ULTRAVIOLET-LIGHT; SEQUENCE-ANALYSIS; OPERON AB Genetic and physiological experiments have demonstrated that the products of the umu-like operon are directly required for mutagenic DNA repair in enterobacteria. To date, five such operons have been cloned and studied at the molecular level. Given the apparent wide occurrence of these mutagenic DNA repair genes in enterobacteria, it seems likely that related genes will be identified in other bacterial species and perhaps even in higher organisms. We are interested in identifying such genes. However, standard methods based on either DNA or protein cross-hybridization are laborious and, given the overall homology between previously identified members of this family (41 to 83% at the protein level), would probably have limited success. To facilitate the rapid identification of more diverse umu-like genes, we have constructed two Escherichia coli strains that allow us to identify umu-like genes after phenotypic complementation assays. With these two strains, we have cloned novel umu-like genes from three R plasmids, the IncJ plasmid R391 and two IncL/M plasmids, R446b and R471a. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BETHESDA,MD 20892. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 60 TC 73 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 SEP PY 1993 VL 175 IS 17 BP 5411 EP 5419 PG 9 WC Microbiology SC Microbiology GA LV387 UT WOS:A1993LV38700016 PM 8366028 ER PT J AU PARK, JB ASHIZAWA, K PARKISON, C CHENG, SY AF PARK, JB ASHIZAWA, K PARKISON, C CHENG, SY TI ONE-STEP IMMUNOAFFINITY PURIFICATION OF HUMAN BETA-1 THYROID-HORMONE RECEPTOR WITH DNA AND HORMONE-BINDING ACTIVITY SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE THYROID HORMONE; THYROID HORMONE RESPONSE ELEMENT; THYROID HORMONE NUCLEAR RECEPTOR; RETINOID-X RECEPTOR; IMMUNOABSORPTION; AFFINITY CHROMATOGRAPHY ID RETINOIC ACID; RAT-LIVER; HETERODIMERIZATION; ACTIVATION AB An efficient and versatile method to purify large amounts of active human beta1 thyroid hormone receptor (h-TRbeta1) was developed. Using a T7 expression system, h-TRbeta1 was overexpressed in Escherichia coli. Approx. 80% of the expressed receptor protein was concentrated in the insoluble inclusion bodies and approximately 20% was in the soluble form (h-TRbeta1-S). h-TRbeta1-S was.conveniently purified by one immunoaffinity chromatographic step. From 1 l of cell culture, approx. 0.1 mg of purified h-TRbeta1-S was obtained. The purified h-TRbeta1-S binds to 3,3',5-triiodo-L-thyronine with a K(a) = 2.10(9) M-1 and exhibits analog specificity. The purified h-TRbeta1-S also binds to T3 response elements (TRE) with different orientation in the half-sites with differential activity. In addition, binding of h-TRbeta1-S to TREs was enhanced by retinoid X receptor. These results indicate that the purified h-TRbeta1-S retains its hormone and DNA binding activity. The purified h-TRbeta1-S is suitable for structural and functional studies. This method could be used to purify h-TRbeta1 or rat TRbeta1 expressed in insect cells or yeast. C1 NCI,DCBDC,MOLEC BIOL LAB,GENE REGULAT SECT,9000 ROCKVILLE PIKE,37-4B09,BETHESDA,MD 20892. NR 13 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD SEP PY 1993 VL 27 IS 2 BP 95 EP 103 DI 10.1016/0165-022X(93)90053-Q PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LX815 UT WOS:A1993LX81500002 PM 8227948 ER PT J AU INGRAM, RT CLARKE, BL FISHER, LW FITZPATRICK, LA AF INGRAM, RT CLARKE, BL FISHER, LW FITZPATRICK, LA TI DISTRIBUTION OF NONCOLLAGENOUS PROTEINS IN THE MATRIX OF ADULT HUMAN BONE - EVIDENCE OF ANATOMIC AND FUNCTIONAL-HETEROGENEITY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GAMMA-CARBOXYGLUTAMIC ACID; GROWTH-FACTOR-BETA; SMALL PROTEOGLYCAN-I; CALF BONE; IMMUNOHISTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL IMMUNOLOCALIZATION; OSTEOGENESIS IMPERFECTA; MONOCLONAL-ANTIBODIES; OSTEONECTIN; OSTEOPONTIN AB The microanatomic distribution of several noncollagenous proteins (NCPs) in bone matrix was examined by immunohistochemical analysis of glycol-methyl methacrylate-embedded normal adult human bone biopsies. Osteopontin and bone sialoprotein stained throughout the lamellae of both trabecular and cortical bone. Cement fines (cortical and trabecular) and the mineralized matrix immediately adjacent to each Haversian canal were intensely stained. Osteocalcin was detected in cement lines; however, lamellar staining varied depending on the location within the individual unit of bone. In cortical bone, the inner concentric lamellae of osteons were often unstained but the outer lamellae were heavily stained for osteocalcin. Osteonectin was not detected in cement lines and in most specimens revealed a pattern similar to that of osteocalcin with respect to the absence of immunostaining within the inner concentric lamellae. Decorin was prominent in the perilacunar matrix, the canaliculi of osteocytes, and the matrix immediately adjacent to quiescent Haversian canals. Biglycan appeared evenly distributed throughout cortical and trabecular bone matrix. These results suggest that the incorporation of NCPs into matrix may vary depending on the stage of formation of individual bone units. The specific distribution and spatial relationship of these NCPs may be related to the function of each protein during bone resorption and formation. The distinct patterns of NCP localization in bone support the hypothesis that in addition to their structural and mineral-inducing properties, these proteins may influence the events associated with bone remodeling, such as recruitment, attachment, differentiation, and activity of bone cells. C1 MAYO CLIN & MAYO FDN,DEPT INTERNAL MED,ENDOCRINE RES UNIT,5-164 W JOSEPH BLDG,ROCHESTER,MN 55905. NIDR,BETHESDA,MD 20892. NR 61 TC 125 Z9 128 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1993 VL 8 IS 9 BP 1019 EP 1029 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LU336 UT WOS:A1993LU33600001 PM 8237471 ER PT J AU BELL, NH YERGEY, AL VIEIRA, NE OEXMANN, MJ SHARY, JR AF BELL, NH YERGEY, AL VIEIRA, NE OEXMANN, MJ SHARY, JR TI DEMONSTRATION OF A DIFFERENCE IN URINARY CALCIUM, NOT CALCIUM-ABSORPTION, IN BLACK-AND-WHITE ADOLESCENTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID D-ENDOCRINE SYSTEM; VITAMIN-D; DIETARY CALCIUM; 1,25-DIHYDROXYVITAMIN-D; CHROMATOGRAPHY; CHILDREN; ASSAY; AGE AB Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck is greater in black than in white children. Studies were performed to determine whether differences in intestinal absorption of calcium or urinary calcium or both account for an assumed more positive calcium balance and greater bone mass in black children. Normal black and white boys and girls were admitted to a metabolic ward and given a constant daily diet containing 1000 mg calcium, 60% as calcium carbonate, for 2 1/2 days (study 1) or 3 1/2 days (study II). Fasting blood and 24 h urine collections were obtained, and in study II, unidirectional fractional absorption of calcium (alpha) was determined with stable isotopes of calcium. It was found that (1) serum 25-hydroxyvitamin D (25-OHD) and urinary calcium were lower and serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was higher in black than in white children, and (2) alpha was higher in boys than in girls with no racial difference, and (3) there were significant positive correlations between alpha and urinary calcium in the blacks and in the black and white children together. It is concluded that (1) alpha is higher in boys than in girls and (2) a lower urinary calcium, not increased intestinal absorption of calcium, is the means for a more positive calcium balance in blacks that accounts for the racial difference in BMD. C1 MED UNIV SO CAROLINA,DEPT MED,CHARLESTON,SC 29401. MED UNIV SO CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29401. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP BELL, NH (reprint author), MED UNIV SO CAROLINA,RALPH H JOHNSON VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. FU NCRR NIH HHS [MO1 RR0170]; NIAMS NIH HHS [R01 AR36066] NR 20 TC 71 Z9 71 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1993 VL 8 IS 9 BP 1111 EP 1115 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LU336 UT WOS:A1993LU33600011 PM 8237481 ER PT J AU VINSON, VK ARCHER, SJ LATTMAN, EE POLLARD, TD TORCHIA, DA AF VINSON, VK ARCHER, SJ LATTMAN, EE POLLARD, TD TORCHIA, DA TI 3-DIMENSIONAL SOLUTION STRUCTURE OF ACANTHAMOEBA PROFILIN-I SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; BOUND ADENOSINE 5'-TRIPHOSPHATE; RESTRAINED MOLECULAR-DYNAMICS; DISTANCE GEOMETRY; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SACCHAROMYCES-CEREVISIAE; N-15-LABELED PROTEINS; HETERONUCLEAR NMR; LARGER PROTEINS; PHOSPHOLIPASE-C AB We have determined a medium resolution three-dimensional solution structure of Acanthamoeba profilin-I by multidimensional nuclear magnetic resonance spectroscopy. This 13-kD actin binding protein consists of a five stranded antiparallel beta sheet flanked by NH2- and COOH-terminal helices on one face and by a third helix and a two stranded beta sheet on the other face. Data from actin-profilin cross-linking experiments and the localization of conserved residues between profilins in different phyla indicate that actin binding occurs on the molecular face occupied by the terminal helices. The other face of the molecule contains the residues that differ between Acanthamoeba profilins-I and II and may be important in determining the difference in polyphosphoinositide binding between these isoforms. This suggests that lipids and actin bind to different faces of the molecule. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS & BIOPHYS CHEM,BALTIMORE,MD 21205. FU NIGMS NIH HHS [GM13620, GM-35171] NR 40 TC 70 Z9 72 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1993 VL 122 IS 6 BP 1277 EP 1283 DI 10.1083/jcb.122.6.1277 PG 7 WC Cell Biology SC Cell Biology GA LY150 UT WOS:A1993LY15000011 PM 8397216 ER PT J AU WARD, GE MILLER, LH DVORAK, JA AF WARD, GE MILLER, LH DVORAK, JA TI THE ORIGIN OF PARASITOPHOROUS VACUOLE MEMBRANE-LIPIDS IN MALARIA-INFECTED ERYTHROCYTES SO JOURNAL OF CELL SCIENCE LA English DT Article DE MALARIA; INVASION; PARASITOPHOROUS VACUOLE MEMBRANE; ERYTHROCYTE ID RED-BLOOD-CELLS; PLASMODIUM-KNOWLESI MEROZOITES; BIOLOGICAL-MEMBRANES; CONTINUOUS CULTURE; FINE-STRUCTURE; INVASION; FALCIPARUM; PARASITE; MECHANISM; ASYMMETRY AB During invasion of an erythrocyte by a malaria merozoite, an indentation develops in the erythrocyte surface at the point of contact between the two cells. This indentation deepens as invasion progresses, until the merozoite is completely surrounded by a membrane known as the parasitophorous vacuole membrane (PVM). We incorporated fluorescent lipophilic probes and phospholipid analogs into the erythrocyte membrane, and followed the fate of these probes during PVM formation with low-light-level video fluorescence microscopy. The concentration of probe in the forming PVM was indistinguishable from the concentration of probe in the erythrocyte membrane, suggesting that the lipids of the PVM are continuous with and derived from the host cell membrane during invasion. In contrast, fluorescently labeled erythrocyte surface proteins were largely excluded from the forming PVM. These data are consistent with a model for PVM formation in which the merozoite induces a localized invagination in the erythrocyte lipid bilayer, concomitant with a localized restructuring of the host cell cytoskeleton. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP WARD, GE (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 53 TC 111 Z9 112 U1 1 U2 4 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 SEP PY 1993 VL 106 BP 237 EP 248 PN 1 PG 12 WC Cell Biology SC Cell Biology GA LZ766 UT WOS:A1993LZ76600024 PM 8270628 ER PT J AU MATSUNAMI, H MIYATANI, S INOUE, T COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M AF MATSUNAMI, H MIYATANI, S INOUE, T COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M TI CELL-BINDING SPECIFICITY OF MOUSE R-CADHERIN AND CHROMOSOMAL MAPPING OF THE GENE SO JOURNAL OF CELL SCIENCE LA English DT Article DE CADHERINS; CELL ADHESION; CELL SORTING; CHROMOSOMAL MAPPING ID N-CADHERIN; ADHESION MOLECULES; EXPRESSION; ORGANIZATION; GENOME; FAMILY; ACID AB R-cadherin was originally identified as a chicken cadherin expressed by the retina. Here, we describe the identification of a mouse homologue of R-cadherin. We isolated mouse cDNAs encoding a cadherin with 94% identity in amino acid sequence to the chicken R-cadherin, and defined this molecule as mouse R-cadherin. L cells transfected with the mouse R-cadherin cDNA acquired a cadherin-mediated cell-cell adhesiveness as found for other cadherins. To examine the binding specificity of mouse R-cadherin, L cells expressing this cadherin (mRL) were mixed with L cells expressing chicken R-cadherin (cRL), mouse N-cadherin (mNL), mouse E-cadherin (mEL) and mouse P-cadherin (mPL). While mRL cells randomly intermixed with cRL cells, those cells aggregated separately from mEL or mPL cells. Mixing of mRL with mNL cells gave an intermediate result; that is, they formed both separate and chimeric aggregates, suggesting that R- and N-cadherin can interact with each other although each has a preference to bind to its own type. Similar properties were previously found for chicken R-cadherin. Thus, the cell binding specificity of R-cadherin is entirety conserved between the two species, suggesting a conserved role for this protein in morphogenesis. We also located the mouse R-cadherin gene to chromosome 2. C1 KYOTO UNIV,FAC SCI,DEPT BIOPHYS,KITASHIRAKAWA,SAKYO KU,KYOTO 60601,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Takeichi, Masatoshi/G-5903-2012 OI Takeichi, Masatoshi/0000-0002-9931-3378 FU NCI NIH HHS [N01-CO-74101] NR 25 TC 76 Z9 78 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1993 VL 106 BP 401 EP 409 PN 1 PG 9 WC Cell Biology SC Cell Biology GA LZ766 UT WOS:A1993LZ76600038 PM 8270638 ER PT J AU VOGEL, T GUO, NH KRUTZSCH, HC BLAKE, DA HARTMAN, J MENDELOVITZ, S PANET, A ROBERTS, DD AF VOGEL, T GUO, NH KRUTZSCH, HC BLAKE, DA HARTMAN, J MENDELOVITZ, S PANET, A ROBERTS, DD TI MODULATION OF ENDOTHELIAL-CELL PROLIFERATION, ADHESION, AND MOTILITY BY RECOMBINANT HEPARIN-BINDING DOMAIN AND SYNTHETIC PEPTIDES FROM THE TYPE-I REPEATS OF THROMBOSPONDIN SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CHEMOTAXIS; EXTRACELLULAR MATRIX; ANGIOGENESIS; BASIC FIBROBLAST GROWTH FACTOR ID LIGAND-BINDING; GROWTH; ANGIOGENESIS; RECEPTOR; MOTIF; GLYCOPROTEIN; ATTACHMENT; INHIBITION; FRAGMENT; PROTEINS AB Thrombospondin is an inhibitor of angiogenesis that modulates endothelial cell adhesion, proliferation, and motility. Synthetic peptides from the second type I repeat of human thrombospondin containing the consensus sequence -Trp-Ser-Pro-Trp- and a recombinant heparin binding fragment from the amino-terminus of thrombospondin mimic several of the activities of the intact protein. The peptides and heparin-binding domain promote endothelial cell adhesion, inhibit endothelial cell chemotaxis to basic fibroblast growth factor (bFGF), and inhibit mitogenesis and proliferation of aortic and corneal endothelial cells. The peptides also inhibit heparin-dependent binding of bFGF to corneal endothelial cells. The antiproliferative activities of the peptides correlate with their ability to bind to heparin and to inhibit bFGF binding to heparin. Peptides containing amino acid substitutions that eliminate heparin-binding do not alter chemotaxis or proliferation of endothelial cells. Inhibition of proliferation by the peptide is time-dependent and reversible. Thus, the antiproliferative activities of the thrombospondin peptides and recombinant heparin-binding domain result at least in part from competition with heparin-dependent growth factors for binding to endothelial cell proteoglycans. These results suggest that both the Trp-Ser-Xaa-Trp sequences in the type I repeats and the amino-terminal domain play roles in the antiproliferative activity of thrombospondin. (C) 1993 Wiley-Liss, Inc.* C1 NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. MEHARRY MED COLL,DEPT BIOCHEM,NASHVILLE,TN 37208. BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NEI NIH HHS [R01 EY09092] NR 36 TC 122 Z9 122 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP PY 1993 VL 53 IS 1 BP 74 EP 84 DI 10.1002/jcb.240530109 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LX306 UT WOS:A1993LX30600008 PM 8227183 ER PT J AU KENNEY, NJ SAEKI, T GOTTARDIS, M KIM, N GARCIAMORALES, P MARTIN, MB NORMANNO, N CIARDIELLO, F DAY, A CUTLER, ML SALOMON, DS AF KENNEY, NJ SAEKI, T GOTTARDIS, M KIM, N GARCIAMORALES, P MARTIN, MB NORMANNO, N CIARDIELLO, F DAY, A CUTLER, ML SALOMON, DS TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA ANTISENSE MESSENGER-RNA INHIBITS THE ESTROGEN-INDUCED PRODUCTION OF TGF-ALPHA AND ESTROGEN-INDUCED PROLIFERATION OF ESTROGEN-RESPONSIVE HUMAN BREAST-CANCER CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; FACTOR-RECEPTOR; FACTOR-BETA; TRANSGENIC MICE; MCF-7 CELLS; MULTIHORMONAL REGULATION; ONCOGENE EXPRESSION; STIMULATED GROWTH; RIBONUCLEIC-ACID; CARCINOMA-CELLS AB To ascertain if 17beta-estradiol (E2)-induced proliferation could be attenuated by blocking the expression of endogenous transforming growth factor alpha (TGFalpha), estrogen receptor (ER)-positive, estrogen-responsive MCF-7 or ZR-75-1 cells and ER-negative, estrogen-nonresponsive MDA-MB-468 or HS-578T cells were infected with a recombinant amphotropic, replication-defective retroviral expression vector containing a 435 base pair (bp) Apa1-Eco R1 coding fragment of the human TGFalpha cDNA oriented in the 3' to 5' direction and under the transcriptional control of an internal heavy metal-inducible mouse metallothionein (MT-1) promoter and containing the neomycin (neo) resistance gene. E2-stimulated expression of endogenous TGFalpha mRNA was inhibited by 4-5-fold, and the production of TGFalpha protein was inhibited by 50-80% when M-1 mass-infected MCF-7 or MZ-1 mass-infected ZR-75-1 cells were treated with 0.75-1 muM CdCl2, whereas in comparably treated parental MCF-7 or ZR-75-1 cells there was no significant effect upon these parameters. E2-stimulated anchorage-dependent growth (ADG) and anchorage-independent growth (AIG) of the M-1 or MZ-1 cells was inhibited by 60-90% following CdCl2 treatment. In contrast, neither the ADG nor AIG of the parental noninfected MCF-7 or ZR-75-1 cells that were maintained in the absence or presence of E2 was affected by comparable concentrations of CdCl2. The ADG and AIG of TGFalpha antisense MD-1 mass-infected MDA-MB-468 cells that express high levels of endogenous TGFalpha mRNA were also inhibited by 1 muM CdCl2, whereas the ADG and AIG of MH-1 mass-infected HS-578T cells, a TGFalpha-negative cell line, were unaffected by CdCl2 treatment. These results suggest that TGFalpha may be one important autocrine intermediary in regulating estrogen-induced cell proliferation. (C) 1993 Wiley-Liss, Inc. C1 NCI,DIV CANC BIOL DIAGN,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT MICROBIOL,WASHINGTON,DC 20001. HIROSHIMA UNIV,DEPT SURG,NUCL MED & BIOL RES INST,MINAMI KU,HIROSHIMA 734,JAPAN. GEORGETOWN UNIV HOSP,VINCENT LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. FAC NAPOLI 2,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. NR 83 TC 63 Z9 64 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1993 VL 156 IS 3 BP 497 EP 514 DI 10.1002/jcp.1041560309 PG 18 WC Cell Biology; Physiology SC Cell Biology; Physiology GA LU994 UT WOS:A1993LU99400008 PM 8360257 ER PT J AU MATTHEW, E ANDREASON, P CARSON, RE HERSCOVITCH, P PETTIGREW, K COHEN, R KING, C JOHANSON, CE PAUL, SM AF MATTHEW, E ANDREASON, P CARSON, RE HERSCOVITCH, P PETTIGREW, K COHEN, R KING, C JOHANSON, CE PAUL, SM TI REPRODUCIBILITY OF RESTING CEREBRAL BLOOD-FLOW MEASUREMENTS WITH H215O POSITRON EMISSION TOMOGRAPHY IN HUMANS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE H215O POSITRON EMISSION TOMOGRAPHY; NORMALIZATION OF DATA; REGIONS OF INTEREST; REPRODUCIBILITY OF MEASUREMENT; RESTING CEREBRAL BLOOD FLOW ID XE-133 INHALATION; NORMAL VALUES AB Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using (H2O)-O-15 positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g-1 min-1, mean +/- SD) for the first (40.3 +/- 6.4) and second (39.3 +/- 6.5) measurements was not significantly different (mean % difference 2.3 +/- 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left-right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans. C1 NIMH,NEUROSCI BRANCH,CLIN BRAIN IMAGING SECT,CEREBRAL BLOOD FLOW & METAB LAB,BETHESDA,MD 20892. NIMH,DEPT NUCL MED,BETHESDA,MD 20892. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 16 TC 66 Z9 66 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1993 VL 13 IS 5 BP 748 EP 754 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA LT800 UT WOS:A1993LT80000002 PM 8360281 ER PT J AU WALKER, KA JONES, TH FELL, RD AF WALKER, KA JONES, TH FELL, RD TI PHEROMONAL BASIS OF AGGREGATION IN EUROPEAN EARWIG, FORFICULA-AURICULARIA L (DERMAPTERA, FORFICULIDAE) SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE AGGREGATION PHEROMONE; CUTICULAR HYDROCARBONS; FATTY ACIDS; QUINONES; DERMAPTERA; FORFICULIDAE; FORFICULA-AURICULARIA; EUROPEAN EARWIG; SOCIAL BEHAVIOR ID CUTICULAR HYDROCARBONS; SCHISTOCERCA; COLEOPTERA; INSECTS; ADULTS; FRASS; ACIDS AB The aggregation behavior of the European earwig Forficula auricularia was investigated. Bioassays of frass extracts, cuticular washings. and the defensive exudate have been conducted to locate the source of an aggregation pheromone, and aggregation behavior has been demonstrated with extracts of frass and the washings of male cuticular lipids. Chemical investigations revealed the presence of a unique pattern of typical normal, monomethyl-, and dimethylalkanes, along with a series of fatty acids and the well-known defensive quinones from these insects. It has been concluded from the bioassays of a number of authentic compounds and the lack of a chemically discernible difference between male and female extracts that the aggregation pheromone of F. auricularia is quite probably a minor component of the male cuticular lipids, C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20852. RP WALKER, KA (reprint author), VIRGINIA TECH,DEPT ENTOMOL,BLACKSBURG,VA 24061, USA. NR 29 TC 20 Z9 22 U1 1 U2 14 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD SEP PY 1993 VL 19 IS 9 BP 2029 EP 2038 DI 10.1007/BF00983805 PG 10 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA LW832 UT WOS:A1993LW83200016 PM 24249377 ER PT J AU HERMAN, BH ASLESON, GS POWELL, A BORGHESE, IF RUCKMAN, R FITZGERALD, C AF HERMAN, BH ASLESON, GS POWELL, A BORGHESE, IF RUCKMAN, R FITZGERALD, C TI CARDIOVASCULAR AND OTHER PHYSICAL EFFECTS OF ACUTE ADMINISTRATION OF NALTREXONE IN AUTISTIC-CHILDREN SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB The physical side effects of acutely administered naltrexone (0.5, 1.0, 1.5, and 2.0 mg/kg, orally) were compared with placebo in 13 children (3-12 years old) with autism. Heart rate, systolic blood pressure, mean arterial blood pressure, and axillary body temperature were obtained before and 1 h after placebo or drug administration. Serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase(SGPT) were obtained 1 h and 24 h after drug. In comparison with placebo, no significant effects of any of the four doses of naltrexone were found on any of these measures. Three hours after administration, there were no significant effects of acute naltrexone on EKG parameters (heart rate, axis, PR, QRS, QT, or QTc) compared to predrug values. These data support the safety of acute administration of naltrexone on vital signs, EKG, and liver function in preadolescent children with autism and are consistent with studies in healthy normotensive adults. In view of prior findings that naltrexone can alter cardiovascular function in certain pathologic states (including some that involve increased opioid peptide activity) and findings of increased opioid activity in some autistic individuals, the absence of cardiovascular effects of naltrexone in autistic children is tentatively suggestive of the safety of acutely administered naltrexone. Since chronic high doses of naltrexone can increase liver transaminase levels in adults, it remains advisable for clinicians to monitor liver function in children receiving chronic naltrexone treatment. Other adverse effects of acute naltrexone in these children appeared to be minimal. RP HERMAN, BH (reprint author), NIDA,DIV MED DEV,5600 FISHERS LANE,ROOM 11A-55,ROCKVILLE,MD 20857, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 1993 VL 3 IS 3 BP 157 EP 168 DI 10.1089/cap.1993.3.157 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA MN986 UT WOS:A1993MN98600004 PM 19630675 ER PT J AU FEUILLAN, PP JONES, J CUTLER, GB AF FEUILLAN, PP JONES, J CUTLER, GB TI LONG-TERM TESTOLACTONE THERAPY FOR PRECOCIOUS PUBERTY IN GIRLS WITH THE MCCUNE-ALBRIGHT SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-RELEASING HORMONE; ULTRASONOGRAPHY; PLASMA AB We used the aromatase inhibitor testolactone (40 mg/kg.day) to treat 12 girls with precocious puberty due to the McCune-Albright syndrome for periods of 0.5-5 yr. In the 7 girls who received testolactone for at least 3 yr, the mean +/- SD serum estradiol level was 618 +/- 268 pmol/L at the start of therapy and fell to 156 +/- 84 pmol/L at 1 yr, 116 +/- 48 pmol/L at 2 yr, and 241 +/- 260 pmol/L at 3 yr (P < 0.05 compared to the start of therapy), with recurrent ovarian cysts at 3 yr in 2 patients. These 7 girls averaged 8 menses/yr before therapy. The average frequency of menses decreased to 2 episodes/yr during the first year of treatment, 3/yr during the second year, and 4/yr during the third year. The mean +/- SD testosterone levels were slightly above the normal prepubertal range (0.51 +/- 0.2 nmol/L) before treatment and did not change significantly during treatment. The mean +/- SD androstenedione levels rose from 1.1 +/- 0.6 nmol/L before treatment to 2.1 +/- 0.1 nmol/L at 2 yr and 2.8 +/- 0.1 nmol/L after 3 yr of treatment (P < 0.05 compared to before treatment) and were consistent with normal adrenarche. The mean predicted adult stature was 143.0 +/- 7.8 cm before treatment and 147.3 +/- 11.5 cm at 3 yr (P = NS). In 3 of 12 girls, all with bone age greater than 12 yr, the gonadotropin responses to LHRH indicated early central precocious puberty after 1-4 yr of treatment. The adverse effects of testolactone were transient abdominal pain, headache, and diarrhea in 3 girls and elevated hepatic enzymes in 1 girl who had abnormal liver function before treatment. Six families acknowledged difficulty in adhering to the daily dosing schedule. We conclude that testolactone can be effective in the treatment of LHRH-independent precocious puberty in girls with McCune-Albright syndrome, but that some patients exhibit an escape from the effects of treatment after 1-3 yr. RP FEUILLAN, PP (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N 262, BETHESDA, MD 20892 USA. NR 17 TC 60 Z9 62 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1993 VL 77 IS 3 BP 647 EP 651 DI 10.1210/jc.77.3.647 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LX033 UT WOS:A1993LX03300015 PM 8370686 ER PT J AU NITYANAND, S SINGH, VK SHINOHARA, T PAUL, AK SINGH, V AGARWAL, PK AGARWAL, SS AF NITYANAND, S SINGH, VK SHINOHARA, T PAUL, AK SINGH, V AGARWAL, PK AGARWAL, SS TI CELLULAR IMMUNE-RESPONSE OF PATIENTS WITH UVEITIS TO PEPTIDE-M, A RETINAL S-ANTIGEN FRAGMENT SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE LYMPHOCYTE PROLIFERATION ASSAY; PEPTIDE-M; YEAST HISTONE H3; RETINAL S-ANTIGEN; UVEITIS ID EXPERIMENTAL AUTOIMMUNE UVEITIS; MYELIN BASIC-PROTEIN; LYMPHOCYTE CROSS-REACTION; MOLECULAR MIMICRY; UVEITOPATHOGENIC SITE; MULTIPLE-SCLEROSIS; SEQUENCE HOMOLOGY; ALPHA-TRANSDUCIN; BOVINE RETINA; GUINEA-PIGS AB Peptide M, an 18-amino acid fragment from position 303 to position 320 of retinal S-antigen, produces experimental autoimmune uveitis (EAU), similar to that produced by native S-antigen, in several vertebrate species including nonhuman primates. It was observed that 12 of the 39 (30.7%) patients with uveitis, 1 of the 29 (3.4%) patients with systemic connective tissue disorders (CTD) without eye involvement, 2 of the 7 (5.8%) patients of CTD with uveitis, 1 of the 17 (5.8%) patients with diabetic retinopathy, and none of the 19 normal healthy controls showed a significant lymphoproliferative response to peptide M (stimulation index of 3 or more). Yeast histone H3 peptide gave a positive response in 1 (2.5%), 2 (6.8%), 1 (14.2%), 2 (11.7%), and 2 (10.5%) individuals, respectively, in the different groups studied. In a few cases a positive response to yeast histone H3 peptide was observed without significant stimulation to peptide M. These findings indicate that peptide M could also be an immunogenic epitope of S-antigen in humans and be aetiopathologically related to uveitis in a subset of patients with this disease. However, unlike experimental animals, the responses to peptide M and yeast histone H3 were nonconcordant, necessitating further studies. C1 SANJAY GANDHI POST GRAD INST MED SCI,DEPT IMMUNOL,POST BOX 375,RAEBARELI RD,LUCKNOW 226001,INDIA. SITAPUR EYE HOSP,SITAPUR,INDIA. KING GEORGES MED COLL,DEPT OPHTHALMOL,LUCKNOW 226003,UTTAR PRADESH,INDIA. NEI,MOLEC BIOL SECT,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 40 TC 13 Z9 13 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 1993 VL 13 IS 5 BP 352 EP 358 DI 10.1007/BF00920244 PG 7 WC Immunology SC Immunology GA LY060 UT WOS:A1993LY06000008 PM 8245181 ER PT J AU SPIEGEL, AM WEINSTEIN, LS SHENKER, A AF SPIEGEL, AM WEINSTEIN, LS SHENKER, A TI ABNORMALITIES IN G-PROTEIN-COUPLED SIGNAL-TRANSDUCTION PATHWAYS IN HUMAN-DISEASE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; NEPHROGENIC DIABETES-INSIPIDUS; NIH 3T3 CELLS; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; HEREDITARY OSTEODYSTROPHY; MALIGNANT TRANSFORMATION; RECEPTOR; GENE RP SPIEGEL, AM (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,RM 9N-222,BETHESDA,MD 20892, USA. OI Weinstein, Lee/0000-0002-1899-5152 NR 65 TC 117 Z9 123 U1 0 U2 3 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 SEP PY 1993 VL 92 IS 3 BP 1119 EP 1125 DI 10.1172/JCI116680 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LX770 UT WOS:A1993LX77000004 PM 8397218 ER PT J AU GASPARI, AA FLEISHER, TA KRAEMER, KH AF GASPARI, AA FLEISHER, TA KRAEMER, KH TI IMPAIRED INTERFERON-PRODUCTION AND NATURAL-KILLER-CELL ACTIVATION IN PATIENTS WITH THE SKIN-CANCER PRONE DISORDER, XERODERMA-PIGMENTOSUM SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CUTANEOUS NEOPLASMS; CYTOKINE DEFECT; INTERFERON INDUCER; NATURAL IMMUNITY; TUMOR SURVEILLANCE ID HUMAN-LEUKOCYTE INTERFERON; NK-CELLS; RETINOIC ACID; TUMOR-GROWTH; MALIGNANT-MELANOMA; BEIGE MICE; DNA-REPAIR; NUDE-MICE; INVIVO; METASTASIS AB Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder with sun sensitivity, markedly increased skin cancer susceptibility, and defective DNA repair without consistently identified symptoms of immune deficiency. We examined natural killer (NK) cell activity and interferon production in peripheral blood lymphocytes (PBL) of eight XP patients who had multiple primary skin cancers. The XP patients had normal numbers of T cells and NK cells, as well as normal lymphokine-activated killer cell activity and normal tumor necrosis factor-alpha production. Unstimulated NK cell function was 40% of normal controls in five XP patients, but was normal in three other XP patients. However, PBL from all the XP patients tested showed no enhancement of NK activity by the interferon inducer, polyinosinic acid:polycytidilic acid (polyIC) but enhancement by interferon-alpha was normal, suggesting an impairment in interferon production. Parallel studies in non-XP skin cancer patients revealed that both unstimulated and polyIC-enhanced NK activity were normal. Further investigation using PBL from XP patients revealed that the production of interferon-gamma after stimulation with interferon inducers (polyIC, interleukin 2, or K562 tumor cells) was 13-43% of normals. These data indicate that XP lymphocytes have a defect in production of interferons and suggest that defective interferon production, as well as DNA repair defects, may play an important role in the susceptibility of XP patients to skin cancer. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP GASPARI, AA (reprint author), UNIV ROCHESTER,SCH MED & DENT,DEPT DERMATOL,BOX 697,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU Intramural NIH HHS [Z01 BC004517-31]; NIAMS NIH HHS [1R29AR40933-01] NR 50 TC 55 Z9 56 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 SEP PY 1993 VL 92 IS 3 BP 1135 EP 1142 DI 10.1172/JCI116682 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LX770 UT WOS:A1993LX77000006 PM 7690772 ER PT J AU WANG, TC BONNERWEIR, S OATES, PS CHULAK, M SIMON, B MERLINO, GT SCHMIDT, EV BRAND, SJ AF WANG, TC BONNERWEIR, S OATES, PS CHULAK, M SIMON, B MERLINO, GT SCHMIDT, EV BRAND, SJ TI PANCREATIC GASTRIN STIMULATES ISLET DIFFERENTIATION OF TRANSFORMING GROWTH-FACTOR ALPHA-INDUCED DUCTULAR PRECURSOR CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PANCREATIC DUCTS; ISLETS; GASTRIN; TRANSFORMING GROWTH FACTOR-ALPHA ID TRANSGENIC MICE; GASTROINTESTINAL-TRACT; GENE-EXPRESSION; RAT PANCREAS; TGF-ALPHA; FACTOR-I; INSULIN; OVEREXPRESSION; NESIDIOBLASTOSIS; HYPOGLYCEMIA AB Gastrin is transiently expressed in fetal islets during a critical period of their development from protodifferentiated islet precursors in fetal pancreatic ducts. To examine the possible role of gastrin as an islet cell growth factor, postnatal islet growth was studied in transgenic mice which overexpress gastrin and TGFalpha in their pancreas. Overexpression of a TGFalpha transgene causes metaplastic ductules containing numerous insulin expressing cells that resemble protodifferentiated precursors of the fetal pancreas. However, islet mass of the TGFalpha transgenic mice was not increased. Pancreatic overexpression of gastrin from a chimeric insulin/gastrin transgene transcribed from the insulin promoter markedly decreased the TGFalpha-stimulated increase in pancreatic duct mass. Furthermore, pancreatic coexpression of both gastrin and TGFalpha significantly increased islet mass in mice expressing both transgenes. These findings indicate that TGFalpha and gastrin can act synergistically to stimulate islet growth, although neither peptide alone is sufficient. Islet growth may possibly be stimulated through gastrin promoting the differentiation of insulin-positive cells in the TGFalpha-induced metaplastic ducts. This transgenic study suggests that islet neogenesis can be reactivated in the ductular epithelium of the adult pancreas by local expression of two growth factors, gastrin and TGFalpha. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. JOSLIN DIABET CTR,JOSLIN RES CTR,BOSTON,MA 02215. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 44523, DK01937, DK 42147] NR 38 TC 208 Z9 214 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1993 VL 92 IS 3 BP 1349 EP 1356 DI 10.1172/JCI116708 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LX770 UT WOS:A1993LX77000032 PM 8376589 ER PT J AU KANG, SY BENFIELD, DA GORZIGLIA, M SAIF, LJ AF KANG, SY BENFIELD, DA GORZIGLIA, M SAIF, LJ TI CHARACTERIZATION OF THE NEUTRALIZING EPITOPES OF VP7 OF THE GOTTFRIED STRAIN OF PORCINE ROTAVIRUS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEROTYPE-SPECIFIC NEUTRALIZATION; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; GLYCOPROTEIN VP7; RHESUS ROTAVIRUS; NUCLEOTIDE-SEQUENCE; ANIMAL ROTAVIRUSES; SURFACE-PROTEINS; GENE; REACTIVITY AB The neutralization epitopes of the outer capsid protein VP7 of a porcine group A rotavirus were studied by using neutralizing monoclonal antibodies (N-MAbs). Six N-MAbs which were specific for the VP7 protein of the Gottfried strain of porcine rotavirus (serotype G4) were used for analyzing the antigenic sites of VP7. Three different approaches were used for this analysis: testing the serological reactivity of each N-MAb against different G serotypes of human and animal rotaviruses, analyzing N-MAb-resistant viral antigenic variants, and performing a nucleotide sequence analysis of the VP7 gene of each of the viral antigenic variants generated. From the serological analyses, three different reactivity patterns were recognized by plaque reduction virus neutralization and cell culture immunofluorescence tests. A single MAb (RG36H9) reacted with animal rotavirus serotypes G3 and G4 but not with human serotypes G3 and G4. The MAb 57/8 (D. A. Benfield, E. A. Nelson, and Y. Hoshino, p. 111, in Abstr. VIIth Internat. Congr. Virol., 1987, and E. R. Mackow, R. D. Shaw, S. M. Matsui, P. T. Vo, D. A. Benfield, and H. B. Greenberg, Virology 165:511-517, 1988) reacted with animal and human rotavirus serotypes G3 and G4 and also with human serotype G9 and bovine serotype G6. The other four MAbs reacted only with the porcine rotavirus serotype G4. The epitope defined by MAb 57/8 and the epitope defined by the other five MAbs appeared to be partially overlapping or close to each other, as identified by viral antigenic variant analysis. However, data from nucleotide and deduced amino acid sequence analyses of the VP7 of each of the viral antigenic variants showed that these two epitopes constituted a large, single neutralization domain. C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,FOOD ANIM HLTH RES PROGRAM,WOOSTER,OH 44691. S DAKOTA STATE UNIV,DEPT VET SCI,BROOKINGS,SD 57007. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. OI Benfield, David/0000-0001-6492-3830 FU PHS HHS [R01A 133561] NR 35 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1993 VL 31 IS 9 BP 2291 EP 2297 PG 7 WC Microbiology SC Microbiology GA LT813 UT WOS:A1993LT81300007 PM 7691871 ER PT J AU FLORES, J PEREZSCHAEL, I BLANCO, M ROJAS, AM ALFONZO, E CRESPO, I CUNTO, W PITTMAN, AL KAPIKIAN, AZ AF FLORES, J PEREZSCHAEL, I BLANCO, M ROJAS, AM ALFONZO, E CRESPO, I CUNTO, W PITTMAN, AL KAPIKIAN, AZ TI REACTOGENICITY AND IMMUNOGENICITY OF A HIGH-TITER RHESUS ROTAVIRUS-BASED QUADRIVALENT ROTAVIRUS VACCINE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VENEZUELAN INFANTS; MONOCLONAL-ANTIBODIES; REASSORTANT VACCINE; FIELD TRIAL; PROTECTION; SEROTYPE-1; CHILDREN; DIARRHEA; GASTROENTERITIS; ANTIGENICITY AB We evaluated the reactogenicity and antigenicity of a quadrivalent rotavirus vaccine composed of serotype 3 rhesus rotavirus (RRV) and three single-gene-substitution reassortants of RRV and human strain D (D x RRV, serotype 1), DS1 (DS1 x RRV, serotype 2), or ST3 (ST3 x RRV, serotype 4) in a double-masked study with 302 infants in Caracas, Venezuela. Three doses of the quadrivalent vaccine composed of either 10(5) PFU (low titer) or 10(6) PFU (high titer) of each component were administered to 99 and 101 infants, respectively, at 4-week intervals starting at the second month of age; 102 infants received a placebo. Postvaccination reactions were monitored by home visits every other day during the week postvaccination. The vaccine was associated with the occurrence of mild, short-lived febrile episodes in 26 and 23% of the recipients after the first doses of high- or low-titer vaccine, respectively, in comparison with 13% of the infants receiving the placebo. Febrile reactions occurred less frequently in vaccinees after the second or third dose than after the initial dose. The vaccine was not significantly associated with diarrhea or any additional symptom or sign. Serum specimens obtained shortly before the first, 4 weeks after the first, and 4 weeks after the third dose of vaccine or placebo were tested by an immunoglobulin A enzyme-linked immunosorbent assay and by neutralization assays. Seroresponses occurred significantly more often after 3 doses than after a single dose of either vaccine. Immunoglobulin A responses were observed in 80 and 79% of the infants after 3 doses of high- or low-titer vaccine, respectively. Most of the infants tested developed a neutralization response to RRV after 3 doses of the high- (90%) or low-(88%) titer vaccine. Neutralization response rates to human rotavirus serotypes 1 to 4 after 3 doses were similar in both vaccine groups and ranged from 33 to 53%. Overall, 93 of 97 infants receiving the low-titer vaccine and 87 of '' receiving the high-titer vaccine developed seroresponses, as detected by any of the assays employed. The study indicates that 3 doses of quadrivalent vaccine at a titer of 10(6) pFU of each component offered no advantage over the lower-titer preparation for use in efficacy trials. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. MINIST SANIDAD ASISTENCIA SOCIAL,INST BIOMED,CARACAS,VENEZUELA. IBM CORP VENEZUELA,CTR CIENT,CARACAS,VENEZUELA. NR 24 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1993 VL 31 IS 9 BP 2439 EP 2445 PG 7 WC Microbiology SC Microbiology GA LT813 UT WOS:A1993LT81300033 PM 8408569 ER PT J AU GREM, JL JORDAN, E ROBSON, ME BINDER, RA HAMILTON, JM STEINBERG, SM ARBUCK, SG BEVERIDGE, RA KALES, AN MILLER, JA WEISS, RB MCATEE, N CHEN, A GOLDSPIEL, B SOVER, E ALLEGRA, CJ AF GREM, JL JORDAN, E ROBSON, ME BINDER, RA HAMILTON, JM STEINBERG, SM ARBUCK, SG BEVERIDGE, RA KALES, AN MILLER, JA WEISS, RB MCATEE, N CHEN, A GOLDSPIEL, B SOVER, E ALLEGRA, CJ TI PHASE-II STUDY OF FLUOROURACIL, LEUCOVORIN, AND INTERFERON ALFA-2A IN METASTATIC COLORECTAL-CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYINOSINIC-POLYCYTIDYLIC ACID; ATLANTIC ONCOLOGY PROGRAM; CELL-LINES; 5-FLUOROURACIL; COMBINATION; MODULATION; ALPHA-2A; TOXICITY; GAMMA; TRIAL C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSEN CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. USN HOSP,DEPT RADIOL,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. FAIRFAX HEMATOL ONCOL ASSOCIATES,ANNANDALE,VA. NR 34 TC 62 Z9 62 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 SEP PY 1993 VL 11 IS 9 BP 1737 EP 1745 PG 9 WC Oncology SC Oncology GA LW369 UT WOS:A1993LW36900015 PM 8355041 ER PT J AU SAVARESE, DMF DENICOFF, AM BERG, SL HILLIG, M BAKER, SP OSHAUGHNESSY, JA CHOW, C OTTERSON, GA BALIS, FM POPLACK, DG COWAN, KH AF SAVARESE, DMF DENICOFF, AM BERG, SL HILLIG, M BAKER, SP OSHAUGHNESSY, JA CHOW, C OTTERSON, GA BALIS, FM POPLACK, DG COWAN, KH TI PHASE-I STUDY OF HIGH-DOSE PIROXANTRONE WITH GRANULOCYTE-COLONY-STIMULATING FACTOR SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED BREAST; ANTHRAPYRAZOLES; CHEMOTHERAPY; DOXORUBICIN; CANCER; CELLS; PHARMACOLOGY; OXANTRAZOLE; NEUTROPENIA; NSC-349174 C1 NCI,MED BRANCH,MED BREAST CANC SECT,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,DIV ACAD COMP,WORCESTER,MA 01605. RI Baker, Stephen/B-8562-2008 NR 25 TC 10 Z9 10 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 SEP PY 1993 VL 11 IS 9 BP 1795 EP 1803 PG 9 WC Oncology SC Oncology GA LW369 UT WOS:A1993LW36900023 PM 7689093 ER PT J AU JAFFE, ES LONGO, DL AF JAFFE, ES LONGO, DL TI MORE ON FOLLICULAR LYMPHOMAS - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID NON-HODGKINS LYMPHOMAS; ONCOLOGY GROUP RP JAFFE, ES (reprint author), NCI,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1993 VL 11 IS 9 BP 1835 EP 1836 PG 2 WC Oncology SC Oncology GA LW369 UT WOS:A1993LW36900033 ER PT J AU CURTI, BD AF CURTI, BD TI ADOPTIVELY TRANSFERRED ANTI-CD3-ACTIVATED T-CELLS FOR HUMAN TUMOR-IMMUNOTHERAPY - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP CURTI, BD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1993 VL 11 IS 9 BP 1836 EP 1837 PG 2 WC Oncology SC Oncology GA LW369 UT WOS:A1993LW36900035 ER PT J AU RUDORFER, MV AF RUDORFER, MV TI PHARMACOKINETICS OF PSYCHOTROPIC-DRUGS IN SPECIAL POPULATIONS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT SATELLITE SYMP ON CLINIC CROSSFIRE : PARMACOKINETICS AND PSYCHIATRIC DRUGS, AT THE 146TH ANNUAL MEETING OF THE AMERICAN-PSYCHIATRIC-ASSOC CY MAY 25, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID ANTIDEPRESSANT CONCENTRATIONS; CLINICAL PHARMACOKINETICS; RENAL-FAILURE; PSYCHOPHARMACOLOGY; CHILDREN; DISPOSITION; METABOLISM; FLUOXETINE; CHINESE; ADULTS AB Patients treated for psychiatric illness may have a variety of characteristics that alter the pharmacokinetic profiles of psychotropic drugs. Genetic background, age, health status, and personal habits can change the body's ability to absorb, distribute, and metabolize medications. Most psychotropic drugs, with the exception of lithium, are eliminated via biotransformation in the liver rather than renal excretion, and a number of studies have demonstrated distinct phenotypes for hepatic metabolism involving the cytochrome P450 system. ''Slow'' metabolizers are likely to develop higher plasma concentrations of several different classes of psychotropic drugs, including tricyclic antidepressants. Advancing age reduces renal function but has little effect on hepatic metabolism. Volume of distribution may also be increased in elderly patients because of their greater percentage of adipose tissue. Ethnic background can significantly influence both drug metabolism and the pharmacodynamics of a variety of drugs. Thus, the physician should carefully consider patient characteristics when prescribing psychotropic medications and should engage in therapeutic drug monitoring when there is any doubt about the plasma drug levels that a given dosing regimen will achieve. RP RUDORFER, MV (reprint author), NIMH,DIV CLIN & TREATMENT RES,CLIN TREATMENT RES BRANCH,ROCKVILLE,MD 20857, USA. NR 23 TC 29 Z9 29 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1993 VL 54 IS 9 SU S BP 50 EP 54 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ME183 UT WOS:A1993ME18300006 PM 8407858 ER PT J AU PRESKHORN, SH RUDORFER, MV GREENBLATT, DJ NELSON, JC JANICAK, PG AF PRESKHORN, SH RUDORFER, MV GREENBLATT, DJ NELSON, JC JANICAK, PG TI CLINICAL CROSSFIRE - PHARMACOKINETICS AND PSYCHIATRIC DRUGS - DISCUSSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Discussion C1 UNIV KANSAS,SCH MED,DEPT PSYCHIAT,WICHITA,KS. TUFTS UNIV,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DIV CLIN PHARMACOL,BOSTON,MA 02111. ILLINOIS STATE PSYCHIAT INST,RES INST,CHICAGO,IL 60651. UNIV ILLINOIS,DEPT PSYCHIAT,CHICAGO,IL 60680. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06504. NIMH,DIV CLIN & TREATMENT RES,CLIN TREATMENT RES BRANCH,ROCKVILLE,MD 20857. RP PRESKHORN, SH (reprint author), ST FRANCIS REG MED CTR,PSYCHIAT RES INST,1100 N ST,WICHITA,KS 67214, USA. RI Preskorn, Sheldon/L-9839-2016 NR 0 TC 6 Z9 6 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1993 VL 54 IS 9 SU S BP 55 EP 56 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ME183 UT WOS:A1993ME18300007 ER PT J AU WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG AF WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG TI SUBCORTICAL CONNECTIONS OF INFERIOR TEMPORAL AREAS TE AND TEO IN MACAQUE MONKEYS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE VISUAL SYSTEM; PULVINAR; STRIATUM; SUPERIOR COLLICULUS; CLAUSTRUM ID LATERAL GENICULATE-NUCLEUS; SUB-CORTICAL STRUCTURES; POSTERIOR PARIETAL CORTEX; MEDIAL THALAMIC LESIONS; BEHAVING RHESUS-MONKEY; MACACA-MULATTA; SUPERIOR COLLICULUS; CEREBRAL-CORTEX; STRIATE CORTEX; HORSERADISH-PEROXIDASE AB To investigate the subcortical connections of inferior temporal cortex, we injected its anterior and posterior portions (Bonin and Bailey's cytoarchitectonic areas TE and TEO, respectively) in 6 rhesus monkeys with retrograde and anterograde tracers. The results indicate that both areas TE and TEO receive nonreciprocal inputs from several thalamic nuclei, including paracentralis, ventralis anterior, centralis, and limitans, and that TE also receives input from reuniens. Additional nonreciprocal inputs to both areas arise from the hypothalamus, basal nucleus of Meynert, dorsal and median raphe, locus coeruleus, and reticular formation. TE and TEO are reciprocally connected with the lateral, medial, and inferior nuclei of the pulvinar and with the ventral portion of the claustrum. The main subcortical nonreciprocal output from TE and TEO is to the striatum and from TEO to the superior colliculus. TE also sends a very limited projection to nucleus medialis dorsalis magnocellularis of the thalamus. Although the connections of areas TE and TEO are overlapping in most subcortical structures, they are partially segregated in the pulvinar, the reticular nucleus of the thalamus, and the striatum. Specifically, relative to those of TE, the projections of TEO are located more laterally in the medial, lateral, and inferior nuclei of the pulvinar, more ventrally in the reticular nucleus, and more caudally in both the ventral putamen and tail and head of the caudate nucleus. (C) 1993 Wiley-Liss, Inc. RP WEBSTER, MJ (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 156 TC 126 Z9 126 U1 3 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 1 PY 1993 VL 335 IS 1 BP 73 EP 91 DI 10.1002/cne.903350106 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA LR891 UT WOS:A1993LR89100005 PM 8408774 ER PT J AU HILL, SC PARKER, CC BRADY, RO BARTON, NW AF HILL, SC PARKER, CC BRADY, RO BARTON, NW TI MRI OF MULTIPLE PLATYSPONDYLY IN GAUCHER DISEASE - RESPONSE TO ENZYME REPLACEMENT THERAPY SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Note DE GAUCHER DISEASE; PLATYSPONDYLY; MAGNETIC RESONANCE IMAGING ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; EOSINOPHILIC GRANULOMA; COMPLICATIONS; SPINE AB Vertebra plana and multiple platyspondyly are complications of aggressive Gaucher disease. Magnetic resonance imaging readily identifies vertebra plana and secondary spinal cord compression. We present a case of a 2-year-old boy with clinically aggressive Type 1 Gaucher disease in whom MRI showed partial reconstitution of the height of a collapsed lumbar vertebral body after 16 months of enzyme replacement therapy. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. HENRY M JACKSON FDN,ROCKVILLE,MD. RP HILL, SC (reprint author), NIH,DEPT DIAGNOST RADIOL,CTR CLIN,BLDG 10,ROOM 1C-660,BETHESDA,MD 20892, USA. NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1993 VL 17 IS 5 BP 806 EP 809 DI 10.1097/00004728-199309000-00026 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LX477 UT WOS:A1993LX47700026 PM 8370839 ER PT J AU TSUTSUMI, O TAKETANI, Y OKA, T AF TSUTSUMI, O TAKETANI, Y OKA, T TI THE UTERINE GROWTH-PROMOTING ACTION OF EPIDERMAL GROWTH-FACTOR AND ITS FUNCTION IN THE FERTILITY OF MICE SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; SUBMANDIBULAR-GLAND; EPITHELIAL-CELLS; FACTOR RECEPTOR; FEMALE MICE; ESTROGEN; PLASMA AB Epidermal growth factor (EGF) levels in the submandibular glands and plasma are increased in pregnant and aged female mice. The possible role of EGF in fertility was studied in virgin and pregnant mice ranging in age from 10 to 90 weeks of age, employing sialoadenectomy, administration of EGF antibody and EGF replacement. The uterine weight in pregnant, 10-week-old, sialoadenectomized mice was significantly less than in normal mice and the administration of EGF antibody to these mice further decreased uterine weight, resulting in an increased rate of abortion. Replacement EGF treatment. in the sialoadenectomized mice prevented these changes. Uterine weight was about 70 mg at 10 weeks of age, and significantly increased from 30 to 80 weeks when it reached a plateau level of 275 mg. These changes closely followed the increase in the concentration of EGF in the submandibular glands and plasma and coincided with the decline in fertility. In contrast, uterine weight in the sialoadenectomized mice decreased immediately after the operation and remained at about 50-60 mg throughout the experimental period. Pregnancy, as judged by implantation, was achieved in the sialoadenectomized mice at later ages than in the controls. These findings suggest that elevated EGF levels may have a dual function in the control of fertility via uterine growth, depending on the age of mice. C1 NIDDK,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. RP TSUTSUMI, O (reprint author), UNIV TOKYO,FAC MED,DEPT OBSTET & GYNECOL,BUNKYO KU,HONGO,TOKYO,TOKYO 113,JAPAN. NR 21 TC 20 Z9 20 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 1993 VL 138 IS 3 BP 437 EP 443 DI 10.1677/joe.0.1380437 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG256 UT WOS:A1993MG25600009 PM 8277218 ER PT J AU DANFORTH, DN SGAGIAS, MK AF DANFORTH, DN SGAGIAS, MK TI TUMOR-NECROSIS-FACTOR-ALPHA MODULATES ESTRADIOL RESPONSIVENESS OF MCF-7 BREAST-CANCER CELLS IN-VITRO SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; CYTOMETRIC DNA ANALYSIS; ESTROGEN-RECEPTOR; CYTO-TOXICITY; COLORIMETRIC ASSAY; TNF-ALPHA; GROWTH; PROLIFERATION; INVITRO; PROTEIN AB We studied the effect of tumour necrosis factor-alpha (TNF) on oestradiol regulation of growth and metabolism of MCF-7 breast cancer cells to determine whether TNF altered the oestradiol responsiveness of these cells. We found that TNF antagonized oestradiol stimulation of cell growth in a dose-dependent manner, with partial inhibition at l.0 U/ml and complete inhibition at 1000 U/ml. TNF inhibited cell cycle progression, increasing cells in the G(0)G(1) phase and blocking oestradiol-stimulated progression into the S phase. We examined the effect of TNF on three oestrogen-regulated proteins, the oestrogen receptor (ER), the progesterone receptor (PR) and insulin-like growth factor-I (IGF-I). TNF down-regulated the ER and up-regulated the PR. Both of these processes were enhanced by the addition of oestradiol. The effects of TNF on the ER and PR were dose-dependent and occurred without a change in the Kd of the receptor. TNF did not change the respective steady-state mRNA levels. In addition, TNF did not alter secretion of IGF-I either ill the absence or presence of oestradiol, indicating that the effects of TNF on oestrogen-regulated proteins is selective. These findings indicate all important interaction between the immune and endocrine systems. The cytokine TNF has a prominent effect on oestradiol stimulation of MCF-7 cells, blocking its proliferative response and enhancing certain metabolic effects. These actions may be mediated in part through modulation of the ER, although other pathways appear to be involved. RP DANFORTH, DN (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B38,BETHESDA,MD 20892, USA. NR 40 TC 22 Z9 22 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 1993 VL 138 IS 3 BP 517 EP 528 DI 10.1677/joe.0.1380517 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG256 UT WOS:A1993MG25600018 PM 8277225 ER PT J AU HOHMAN, TC BOWERS, B AF HOHMAN, TC BOWERS, B TI HYDROLASE COMPARTMENTALIZATION LIMITS RATE OF DIGESTION IN ACANTHAMOEBA SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE LYSOSOMAL ENZYMES; MEMBRANE FUSION ID MEMBRANE; PHOSPHORYLATION; PINOCYTOSIS; CASTELLANII; ENDOCYTOSIS; PLASMA; FUSION AB The kinetics of lysosomal enzyme acquisition by newly formed phagosomes was studied by following the rate of digestion of radiolabeled yeast fed to Acanthamoeba. The distribution of hydrolases among phagosomes was assessed by electron microscopic acid phosphatase cytochemistry and by measurement of three glycosidases in isolated early and late phagosomes. The results show that compartmentalization of hydrolases limit the digestion of large phagocytic loads. The hydrolases appear to be sequestered into the early phagosomes and not to be distributed either by small vesicle transport or phagosome-phagosome fusion to those formed later. We infer from these results that newly internalized surface membrane in phagosomes is not rapidly randomized with internal pools, but is recycled to the surface as a function of the digestive process. C1 NHLBI,CELL BIOL LAB,BLDG 3,ROOM B1-22,BETHESDA,MD 20892. NR 18 TC 2 Z9 2 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1993 VL 40 IS 5 BP 589 EP 593 DI 10.1111/j.1550-7408.1993.tb06112.x PG 5 WC Microbiology SC Microbiology GA MA332 UT WOS:A1993MA33200008 PM 8401472 ER PT J AU STAIANOCOICO, L KRUEGER, JG RUBIN, JS DLIMI, S VALLAT, VP VALENTINO, L FAHEY, T HAWES, A KINGSTON, G MADDEN, MR MATHWICH, M GOTTLIEB, AB AARONSON, SA AF STAIANOCOICO, L KRUEGER, JG RUBIN, JS DLIMI, S VALLAT, VP VALENTINO, L FAHEY, T HAWES, A KINGSTON, G MADDEN, MR MATHWICH, M GOTTLIEB, AB AARONSON, SA TI HUMAN KERATINOCYTE GROWTH-FACTOR EFFECTS IN A PORCINE MODEL OF EPIDERMAL WOUND-HEALING SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FACTOR-BETA; FACTOR-ALPHA; TISSUE-REPAIR; FACTOR FAMILY; TGF-BETA; EXPRESSION; COLLAGEN; MATRIX; CELLS; FIBRONECTIN AB Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is produced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial-thickness wounds, KGF stimulated the rate of reepithelialization (p <0.0002), associated with a thickening of the epidermis (p <0.0001). Epidermis from KGF-treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p <0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a deep rete ridge pattern as compared with control sites. These effects were observed as early as 14 d and persisted for at least 4 wk. KGF treatment also increased the number of serrated basal cells associated with increased deposition of collagen fibers in the superficial dermis adjacent to the acanthotic epidermis. Electron microscopy revealed better developed hemidesmosomes associated with thicker bundles of tonofilaments in the serrated cells. The pattern of epidermal thickening observed in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperproliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic maturation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation. C1 ROCKEFELLER UNIV,INVESTIGAT DERMATOL LAB,NEW YORK,NY 10021. NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP STAIANOCOICO, L (reprint author), CORNELL UNIV,MED CTR,COLL MED,DEPT SURG,1300 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-54215]; NIGMS NIH HHS [GM-42461, GM-26145] NR 46 TC 159 Z9 162 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 SEP 1 PY 1993 VL 178 IS 3 BP 865 EP 878 DI 10.1084/jem.178.3.865 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LU309 UT WOS:A1993LU30900011 PM 8350059 ER PT J AU MALNATI, MS LUSSO, P CICCONE, E MORETTA, A MORETTA, L LONG, EO AF MALNATI, MS LUSSO, P CICCONE, E MORETTA, A MORETTA, L LONG, EO TI RECOGNITION OF VIRUS-INFECTED CELLS BY NATURAL-KILLER-CELL CLONES IS CONTROLLED BY POLYMORPHIC TARGET-CELL ELEMENTS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NK CELLS; ALLOANTIGEN RECOGNITION; HUMAN HERPESVIRUS-6; LYMPHOCYTES-T; MOUSE NKR-P1; EXPRESSION; IDENTIFICATION; SUSCEPTIBILITY; SPECIFICITY; MOLECULES AB Natural killer (NK) cells provide a first line of defense against viral infections. The mechanisms by which NK cells recognize and eliminate infected cells are still largely unknown. To test whether target cell elements contribute to NK cell recognition of virus-infected cells, human NK cells were cloned from two unrelated donors and assayed for their ability to kill normal autologous or allogeneic cells before and after infection by human herpesvirus 6 (HHV-6), a T-lymphotropic herpesvirus. Of 132 NK clones isolated from donor 1, all displayed strong cytolytic activity against the NK-sensitive cell line K562, none killed uninfected autologous T cells, and 65 (49%) killed autologous T cells infected with HHV-6. A panel of representative NK clones from donors 1 and 2 was tested on targets obtained from four donors. A wide heterogeneity was observed in the specificity of lysis of infected target cells among the NK clones. Some clones killed none, some killed only one, and others killed more than one of the different HHV-6-infected target cells. Killing of infected targets was not due to complete absence of class I molecules because class I surface levels were only partially affected by HHV-6 infection. Thus, target cell recognition is not controlled by the effector NK cell alone, but also by polymorphic elements on the target cell that restrict NK cell recognition. Furthermore, NK clones from different donors display a variable range of specificities in their recognition of infected target cells. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. IST NAZL RIC CANC,I-16132 GENOA,ITALY. RP MALNATI, MS (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK II,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 46 TC 68 Z9 69 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1993 VL 178 IS 3 BP 961 EP 969 DI 10.1084/jem.178.3.961 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LU309 UT WOS:A1993LU30900021 PM 8394407 ER PT J AU BLOCK, MI BERG, M MCNAMARA, MJ NORTON, JA FRAKER, DL ALEXANDER, HR AF BLOCK, MI BERG, M MCNAMARA, MJ NORTON, JA FRAKER, DL ALEXANDER, HR TI PASSIVE-IMMUNIZATION OF MICE AGAINST D-FACTOR BLOCKS LETHALITY AND CYTOKINE RELEASE DURING ENDOTOXEMIA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID LEUKEMIA-INHIBITORY FACTOR; TUMOR-NECROSIS-FACTOR; FACTOR LIF; BLASTOCYST IMPLANTATION; DIFFERENTIATION FACTOR; FACTOR PROTECTION; MESSENGER-RNA; SEPTIC SHOCK; CELLS; EXPRESSION AB D factor, also known as leukemia inhibitory factor, is a pleiotropic cytokine whose role during acute injury and inflammation is not known. Intraperitoneal administration of Escherichia coli endotoxin induced D factor gene expression in mice, and passive immunization against D factor protected them from the lethal effects of endotoxin and blocked endotoxin-induced increases in serum levels of interleukin 1 and 6. Peak levels of tumor necrosis factor and interferon gamma were not affected. These results indicate that D factor is an essential early mediator of the inflammatory cytokine response and therefore may be important in the pathogenesis of the many inflammatory conditions, such as sepsis, arthritis, allograft rejection, and cancer immunotherapy. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B17,BETHESDA,MD 20892. NR 36 TC 40 Z9 41 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1993 VL 178 IS 3 BP 1085 EP 1090 DI 10.1084/jem.178.3.1085 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LU309 UT WOS:A1993LU30900034 PM 8350047 ER PT J AU GAMBASSI, G HANSFORD, RG SOLLOTT, SJ HOGUE, BA LAKATTA, EG CAPOGROSSI, MC AF GAMBASSI, G HANSFORD, RG SOLLOTT, SJ HOGUE, BA LAKATTA, EG CAPOGROSSI, MC TI EFFECTS OF ACIDOSIS ON RESTING CYTOSOLIC AND MITOCHONDRIAL CA2+ IN MAMMALIAN MYOCARDIUM SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID RAT CARDIAC MYOCYTES; CHICK HEART-CELLS; SINGLE VENTRICULAR MYOCYTES; NA+-H+ EXCHANGE; SARCOPLASMIC-RETICULUM; GUINEA-PIG; INTRACELLULAR PH; PURKINJE-FIBERS; CALCIUM TRANSIENTS; CA-2+ RELEASE AB Acidosis increases resting cytosolic [Ca2+], (Ca(i)) of myocardial preparations; however, neither the Ca2+ sources for the increase in Ca(i) nor the effect of acidosis on mitochondrial free [Ca2+], (Ca(m)) have been characterized. In this study cytosolic pH (pH(i)) was monitored in adult rat left ventricular myocytes loaded with the acetoxymethyl ester (AM form) of SNARF-1. A stable decrease in the pH(i) of 0.52 +/- 0.05 U (n = 16) was obtained by switching from a bicarbonate buffer equilibrated with 5% CO2 to a buffer equilibrated with 20% CO2. Electrical stimulation at either 0.5 or 1.5 Hz had no effect on pH(i) in 5% CO2, nor did it affect the magnitude of pH(i) decrease in response to hypercarbic acidosis. Ca(i) was measured in myocytes loaded with indo-1/free acid and Ca(m) was monitored in cells loaded with indo-1/AM after quenching cytosolic indo-I fluorescence with MnCl2. In quiescent intact myocytes bathed in 1.5 mM [Ca2+], hypercarbia increased Ca(i) from 130 +/- 5 to 221 +/- 13 nM. However, when acidosis was effected in electrically stimulated myocytes, diastolic Ca(i) increased more than resting Ca(i) in quiescent myocytes, and during pacing at 1.5 Hz diastolic Ca(i) was higher (285 +/- 17 nM) than at 0.5 Hz (245 +/- 18 nM; P < 0.05). The magnitude of Ca(i) increase in quiescent myocytes was not affected either by sarcoplasmic reticulum (SR) Ca2+ depletion with ryanodine or by SR Ca2+ depletion and concomitant superfusion with a Ca2+-free buffer. In unstimulated intact myocytes hypercarbia increased Ca(m) from 95 +/- 12 to 147 +/- 19 nM and this response was not modified either by ryanodine and a Ca2+-free buffer or by 50 muM ruthenium red in order to block the mitochondrial uniporter. In mitochondrial suspensions loaded either with BCECF/AM or indo-1/AM, acidosis produced by lactic acid addition decreased both intra- and extramitochondrial pH and increased Ca(m). Studies of mitochondrial suspensions bathed in indo-1/free acid-containing solution showed an increase in extramitochondrial Ca2+ after the addition of lactic acid. Thus, in quiescent myocytes, cytoplasmic and intramitochondrial buffers, rather than transsarcolemmal Ca2+ influx or SR Ca2+ release, are the likely Ca2+ sources for the increase in Ca(i) and Ca(m), respectively; additionally, Ca2+ efflux from the mitochondria may contribute to the raise in Ca(i). In contrast, in response to acidosis, diastolic Ca(i) in electrically stimulated myocytes increases more than resting Ca(i) in quiescent cells; this suggests that during pacing, net cell Ca2+ gain contributes to enhance diastolic Ca(i). C1 NIA,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 54 TC 33 Z9 33 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD SEP PY 1993 VL 102 IS 3 BP 575 EP 597 DI 10.1085/jgp.102.3.575 PG 23 WC Physiology SC Physiology GA LY897 UT WOS:A1993LY89700008 PM 8245824 ER PT J AU RAJAGOPALAN, S RODRIGUES, M POLK, T WILSON, D CHADER, GJ HAYDEN, BJ AF RAJAGOPALAN, S RODRIGUES, M POLK, T WILSON, D CHADER, GJ HAYDEN, BJ TI MODULATION OF RETINOBLASTOMA CELL CHARACTERISTICS BY HEXAMETHYLENE BIS-ACETAMIDE AND OTHER DIFFERENTIATING AGENTS IN CULTURE SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE RETINOBLASTOMA; Y-79; IMMUNOCYTOCHEMISTRY; DIFFERENTIATION ID MICROTUBULE-ASSOCIATED PROTEIN-2; ATTACHMENT CULTURE; EXPRESSION; Y-79; BISACETAMIDE; BUTYRATE; LINE; IMMUNOHISTOCHEMISTRY; ONCOGENESIS; WERI-RB1 AB The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for ''neuronal'' and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (T(Ralpha) and T(Calpha))] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of T(Ralpha) was minimal under all culture conditions, whereas T(Calpha) was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used. C1 UNIV MARYLAND,DEPT OPHTHALMOL,MSTF 500-B,10 S PINE ST,BALTIMORE,MD 21201. NEI,DEPT RETINAL CELL & MOLEC BIOL,BETHESDA,MD 20892. NR 41 TC 7 Z9 7 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1993 VL 41 IS 9 BP 1331 EP 1337 PG 7 WC Cell Biology SC Cell Biology GA LT935 UT WOS:A1993LT93500006 PM 8394854 ER PT J AU ENK, AH ANGELONI, VL UDEY, MC KATZ, SI AF ENK, AH ANGELONI, VL UDEY, MC KATZ, SI TI INHIBITION OF LANGERHANS CELL ANTIGEN-PRESENTING FUNCTION BY IL-10 - A ROLE FOR IL-10 IN INDUCTION OF TOLERANCE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ULTRAVIOLET-B RADIATION; T-CELLS; PROLIFERATIVE RESPONSE; CYTOKINE PRODUCTION; CYTOCHROME-C; INTERLEUKIN-10; ACTIVATION; SENSITIVITY; MONOCYTES; CLONES AB IL-10 is a product of activated keratinocytes and is released during the induction phase of contact sensitivity. As IL-10 effects have been described as being mediated by APC, we investigated effects of IL-10 on epidermal Langerhans cells (LC), the resident APC in the epidermis. Initial studies failed to demonstrate effects of IL-10 on MHC class II Ag expression by LC or anti-CD3 mAb- or alloantigen-induced LC-dependent T cell proliferation. However, production of IFN-gamma and IL-2, (but not IL-6) was markedly reduced in these assays. When the soluble-protein Ag specific T cell clones AE7 (Th1) and D10.G4 (Th2) were substituted for unprimed T cells, differential effects of IL-10 on T-cell proliferation were observed. Whereas IL-10-pretreated and untreated LC supported Th2 cell proliferation equally well, IL-10-pretreated LC were essentially unable to induce Th1 cell proliferation in response to native protein or peptide Ag. The inhibitory influence of IL-10 on Th1 cells was observed when fresh or 1 day cultured LC were used; 2- or 3-day cultured LC were affected to a much lesser extent by IL-10 pretreatment. Further, coculture experiments using IL-10-pretreated or untreated LC of a different haplotype suggest that IL-10 negatively regulates a costimulatory signal required for induction of Th1 cell proliferation. To assess whether T cells incubated with Ag and IL-10-pretreated LC were responsive to further stimulation, T cells were rescued after 1 day of coculture with IL-10-pretreated LC and restimulated, either immediately or after 1 to 5 days of rest, with untreated LC in the presence of Ag. T cells incubated with IL-10-pretreated LC were found to be anergic, whereas T cells incubated with untreated LC proliferated normally after further stimulation. However, anergic T cells responded vigorously to IL-2. These data indicate that although IL-10-pretreated LC are effective APC for Th2 cells, they fail to induce Th1 cell proliferation and rather induce clonal anergy in these cells. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N-238,BETHESDA,MD 20892. UNIV MAINZ,DERMATOL BRANCH,W-6500 MAINZ,GERMANY. WALTER REED ARMY MED CTR,DEPT DERMATOL,WASHINGTON,DC 20307. NR 26 TC 475 Z9 482 U1 1 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 SEP 1 PY 1993 VL 151 IS 5 BP 2390 EP 2398 PG 9 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400005 PM 8103065 ER PT J AU HUCZKO, EL BODNAR, WM BENJAMIN, D SAKAGUCHI, K ZHU, NZ SHABANOWITZ, J HENDERSON, RA APPELLA, E HUNT, DF ENGELHARD, VH AF HUCZKO, EL BODNAR, WM BENJAMIN, D SAKAGUCHI, K ZHU, NZ SHABANOWITZ, J HENDERSON, RA APPELLA, E HUNT, DF ENGELHARD, VH TI CHARACTERISTICS OF ENDOGENOUS PEPTIDES ELUTED FROM THE CLASS-I MHC MOLECULE HLA-B7 DETERMINED BY MASS-SPECTROMETRY AND COMPUTER MODELING SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; SIGNAL SEQUENCE; VIRAL PEPTIDE; NUCLEIC-ACIDS; FORCE-FIELD; B ANTIGENS; BINDING; COMPLEX; PROTEIN; RESOLUTION AB Microcapillary HPLC electrospray ionization tandem mass spectrometry was used to sequence 15 peptides eluted from HLA-B7. Sequence alignment implicated four peptide positions in specific interactions with the class I molecule, and their importance was confirmed using synthetic peptides. Because no crystal structure for HLA-B7 was available, computer-assisted modeling was used to understand novel aspects of peptide binding specificity and to accurately predict the effect of defined changes in peptide structure. The results demonstrate that mass-spectrometric sequencing coupled with computer-assisted modeling can be used in the absence of a crystal structure to make accurate predictions concerning requirements for peptide binding to class I molecules. These techniques may be valuable to predict or engineer T cell epitopes. C1 UNIV VIRGINIA,BEIRNE CARTER CTR IMMUNOL RES,HLTH SCI CTR MR4,BOX 4012,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22908. NCI,BETHESDA,MD 20892. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIAID NIH HHS [AI20745, AI20963, AI21393] NR 55 TC 171 Z9 171 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1993 VL 151 IS 5 BP 2572 EP 2587 PG 16 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400024 PM 8360479 ER PT J AU LIEBERMAN, SA HINES, MD BERGSAGEL, PL KUEHL, WM ECKHARDT, LA AF LIEBERMAN, SA HINES, MD BERGSAGEL, PL KUEHL, WM ECKHARDT, LA TI COORDINATE SILENCING OF MYELOMA-SPECIFIC GENES IN MYELOMA X T-LYMPHOMA HYBRIDS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN PROMOTER; OCTAMER TRANSCRIPTION FACTORS; TISSUE-SPECIFIC EXTINGUISHER; IMMUNOGLOBULIN J-CHAIN; SOMATIC-CELL HYBRIDS; C-MU GENE; ANTIGEN PC-1; REGULATORY SUBUNIT; SEQUENCE ELEMENTS; DNA METHYLATION AB It has been well-established that Ig genes are transcriptionally silenced when Ig-producing myeloma lines are fused to non-B cells. In the present study, we analyzed the expression of several other myeloma-specific genes in fusions of myelomas with the T lymphoma, BW5147. Seven of the eight genes analyzed behaved coordinately with the Ig loci; they were silent in most myeloma x T hybrids but active in the rare hybrid that retained Ig gene expression. Cloned IgH genes introduced into the two types of hybrids behaved as their endogenous counterparts. The coordinate behavior of these several genes in the panel of ''exceptional'' and ''extinguished'' hybrids suggests a central and bimodal switch for alternately activating and de-activating the genetic program of the Ig-secreting plasmacyte. The switch between an active and an inactive transcriptional state involves, at some level, a change in the methylation status of the IgH genes. Methylation and transcriptional activity were inversely correlated. In Ig-extinguished hybrids the myeloma-derived locus was methylated de novo, whereas in the rare Ig-expressing hybrid, the T cell-derived locus was demethylated de novo. C1 CUNY HUNTER COLL,DEPT BIOL SCI,695 PK AVE,NEW YORK,NY 10021. COLUMBIA UNIV,DEPT BIOL SCI,NEW YORK,NY 10027. NCI,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NIGMS NIH HHS [GM07216] NR 59 TC 13 Z9 13 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 SEP 1 PY 1993 VL 151 IS 5 BP 2588 EP 2600 PG 13 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400025 PM 8360480 ER PT J AU WEISS, WR SEDEGAH, M BERZOFSKY, JA HOFFMAN, SL AF WEISS, WR SEDEGAH, M BERZOFSKY, JA HOFFMAN, SL TI THE ROLE OF CD4(+) T-CELLS IN IMMUNITY TO MALARIA SPOROZOITES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY GK1.5; SUSCEPTIBLE BALB/C MICE; CIRCUMSPOROZOITE PROTEIN; LYMPHOCYTE-T; VIRUS-INFECTION; HELPER-CELLS; INVIVO; ELIMINATION; EPITOPE; CD4+ AB BALB/c mice are strongly protected against malaria after immunization with Plasmodium yoelii (PY) sporozoites, and this is an important model for malaria vaccine development in humans. This paper explores the role of CD4+ cells in the induction of the antimalarial immune response. The method used has been to treat animals with anti-CD4 mAb before immunization, resulting in a profound depletion of CD4+ T cells. The primary finding is that mice are not protected by sporozoite immunization after depletion of CD4+ cells. Such mice make little antibody tb malaria sporozoite Ag, showing the strong T-cell dependence of these humoral responses. However, infusion of hyperimmune serum does not restore immunity to anti-CD4 treated animals. Neither does injection of exogenous IL-2 compensate for the absence of CD4+ cells. However, regrowth of CD4+ cells does allow successful immunization of animals, showing that long-term suppression against malaria Ag has not been induced by immunization in the absence of CD4+ cells. It is thought that infiltrating CD8+ T cells are critical effector cells against PY parasites in the pre-erythrocytic stages. Mice immunized while depleted of CD4+ cells have normal numbers of CD8+ T cells infiltrating their livers. In addition, they have normal numbers of splenic CD8+ CTL directed at the PY circumsporozoite protein. Thus, it appears that although CD8+ cells have been activated in the absence of CD4+ cells, they cannot protect mice against malaria. We conclude that a successful vaccine against the pre-erythrocytic stages of malaria must activate both CD4+ and CD8+ T cells. C1 USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. PAN AMER HLTH ORG,WASHINGTON,DC 20037. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20814. NR 43 TC 59 Z9 59 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 SEP 1 PY 1993 VL 151 IS 5 BP 2690 EP 2698 PG 9 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400034 PM 8103069 ER PT J AU GUSELLA, GL MUSSO, T BOSCO, MC ESPINOZADELGADO, I MATSUSHIMA, K VARESIO, L AF GUSELLA, GL MUSSO, T BOSCO, MC ESPINOZADELGADO, I MATSUSHIMA, K VARESIO, L TI IL-2 UP-REGULATES BUT IFN-GAMMA SUPPRESSES IL-8 EXPRESSION IN HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEUTROPHIL CHEMOTACTIC FACTOR; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-8 GENE-EXPRESSION; HUMAN MONONUCLEAR PHAGOCYTES; STIMULATED HUMAN-MONOCYTES; MESSENGER-RNA EXPRESSION; TNF-ALPHA; INTERFERON-GAMMA; BLOOD MONOCYTES; INDUCTION AB IL-2 has pleiotropic properties and is a potent activator of monocytic functions. Since monocytes are an important source of the chemoattractant cytokine IL-8, we studied the effects of IL-2 on the expression of IL-8 in human monocytes. IL-8 mRNA expression was detectable in resting human monocytes. Treatment of monocytes with IL-2 increased IL-8 mRNA expression by a protein synthesis-independent process. The augmentation of IL-8 mRNA by IL-2 was associated with an increase in IL-8 secretion. The expression of IL-8 mRNA was not a nonspecific response to any stimulus of monocyte activation. In fact, IFN-gamma, which is also a potent monocyte activator, not only failed to induce IL-8 expression but inhibited the stimulation of IL-8 by IL-2. Nuclear run-on experiments demonstrated that both the enhancement of IL-8 mRNA expression and its down-regulation by IFN-gamma occurred at the transcriptional level. These results show for the first time that in fresh human monocytes, IL-8 expression is differentially regulated by IL-2 and IFN-gamma and suggest that the interactions among IL-2, IL-8, and IFN-gamma may be important for the development and control of the inflammatory response. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. KANAZAWA UNIV,INST CANC,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. RP GUSELLA, GL (reprint author), NCI,FREDRICK CANC RES & DEV CTR,DYN CORP,PROGRAMRESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 38 TC 88 Z9 88 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 SEP 1 PY 1993 VL 151 IS 5 BP 2725 EP 2732 PG 8 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400038 PM 8360487 ER PT J AU MAO, SY PFEIFFER, JR OLIVER, JM METZGER, H AF MAO, SY PFEIFFER, JR OLIVER, JM METZGER, H TI EFFECTS OF SUBUNIT MUTATION ON THE LOCALIZATION TO COATED PITS AND INTERNALIZATION OF CROSS-LINKED IGE-RECEPTOR COMPLEXES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; RBL-2H3 MAST-CELLS; IMMUNOGLOBULIN-E; FC RECEPTOR; TRANSFECTED CELLS; BETA-SUBUNIT; CYTOPLASMIC DOMAIN; SURFACE EXPRESSION; SEROTONIN RELEASE AB IgE receptors of mast cells, FcepsilonRI, localize to coated pits and internalize after cross-linking. We investigated whether any one of the receptor's four distinctive cytoplasmic domains regulates these phenomena. COS cells, which lack FcepsilonRI entirely, and P815 mouse mastocytoma cells that lack the alpha and beta subunits of the tetrameric FcepsilonRI (alphabetagamma2), were transfected with wild-type, incomplete, or variant FcepsilonRI. IgE-receptor complexes were observed by electron microscopy. Before cross-linking with anti-IgE gold particles, receptors were not preferentially localized to coated pits, which occupy almost-equal-to 1%. of the cell surface. After cross-linking, up to 10 to 20% of the wild-type and most other receptor variants were in coated pits in transfected P815 cells at any one time. Beta-less variants localized normally but, surprisingly, receptors containing a variant beta subunit showed reduced localization. ''Receptors'' consisting simply of the lipid-anchored ectodomains of the human alpha subunit failed to localize to coated pits. In general, cross-linked receptors that localized to coated pits were progressively internalized, whereas receptors that failed to accumulate in coated pits were not. We conclude that no single cytoplasmic domain of the FcepsilonRI uniquely controls its ligand-induced localization to coated pits and internalization. C1 UNIV NEW MEXICO,SCH MED,DEPT PATHOL,ALBUQUERQUE,NM 87131. RP MAO, SY (reprint author), NIAMS,ARTHRITIS & RHEUMATISM BRANCH,CHEM IMMUNOL SECT,RM 9N 228,BLDG 10,BETHESDA,MD 20892, USA. NR 56 TC 29 Z9 29 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 SEP 1 PY 1993 VL 151 IS 5 BP 2760 EP 2774 PG 15 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400042 PM 8360490 ER PT J AU SPECTOR, SA WEINGEIST, T POLLARD, RB DIETERICH, DT SAMO, T BENSON, CA BUSCH, DF FREEMAN, WR MONTAGUE, P KAPLAN, HJ KELLERMAN, L CRAGER, M DEARMOND, B BUHLES, W FEINBERG, J AF SPECTOR, SA WEINGEIST, T POLLARD, RB DIETERICH, DT SAMO, T BENSON, CA BUSCH, DF FREEMAN, WR MONTAGUE, P KAPLAN, HJ KELLERMAN, L CRAGER, M DEARMOND, B BUHLES, W FEINBERG, J TI A RANDOMIZED, CONTROLLED-STUDY OF INTRAVENOUS GANCICLOVIR THERAPY FOR CYTOMEGALOVIRUS PERIPHERAL RETINITIS IN PATIENTS WITH AIDS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; VIRUS RETINITIS; RETINOPATHY; INFECTIONS; FOSCARNET; DISEASE; TRIAL AB This prospective, randomized, multicenter, controlled trial was designed to evaluate the efficacy and safety of intravenous ganciclovir for the treatment of peripheral cytomegalovirus (CMV) retinitis in patients with AIDS. Patients were randomly assigned to receive either immediate treatment, intravenous ganciclovir, 5 mg/kg twice daily for 14 days followed by 5 mg/kg once daily for 14 weeks, or deferred treatment. Patients randomized to deferred treatment whose retinitis progressed were offered ganciclovir. Of the 22 patients randomized to deferred treatment who were included in the final analysis, 20 were found to have progressive CMV retinitis compared with 10 of the 13 randomized to immediate treatment. The median time to progression in the deferred treatment group, as determined by a masked fundus photography reading center, was 13.5 days compared with 49.5 days in the immediate treatment group (mean +/- SD, 19.3 +/- 4.1 vs. 66.4 +/- 14.0; P = .001, log rank test). These data indicate that ganciclovir delays the progression of CMV peripheral retinitis in persons with AIDS. C1 CALIF PACIFIC MED CTR,SAN FRANCISCO,CA. SYNTEX INC,PALO ALTO,CA 94304. UNIV IOWA,IOWA CITY,IA 52242. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. METHODIST HOSP,HOUSTON,TX 77030. NYU,NEW YORK,NY 10003. RUSH MED COLL,CHICAGO,IL 60612. WASHINGTON UNIV,ST LOUIS,MO 63130. NIAID,DIV AIDS,BETHESDA,MD 20892. RP SPECTOR, SA (reprint author), UNIV CALIF SAN DIEGO,SCH MED,CLIN SCI BLDG,9500 GILMAN DR,MAIL CODE 0672,LA JOLLA,CA 92093, USA. OI Crager, Michael/0000-0002-3594-6299 NR 17 TC 113 Z9 114 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 SEP PY 1993 VL 168 IS 3 BP 557 EP 563 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LU337 UT WOS:A1993LU33700004 PM 8394858 ER PT J AU GRANOFF, DM HOLMES, SJ OSTERHOLM, MT MCHUGH, JE LUCAS, AH ANDERSON, EL BELSHE, RB JACOBS, JL MEDLEY, F MURPHY, TV AF GRANOFF, DM HOLMES, SJ OSTERHOLM, MT MCHUGH, JE LUCAS, AH ANDERSON, EL BELSHE, RB JACOBS, JL MEDLEY, F MURPHY, TV TI INDUCTION OF IMMUNOLOGICAL MEMORY IN INFANTS PRIMED WITH HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID OUTER-MEMBRANE-PROTEIN; HUMAN-ANTIBODY RESPONSE; CHAIN VARIABLE REGION; HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; IMMUNOGENICITY; IMMUNIZATION; OLIGOSACCHARIDE; CHILDREN; EFFICACY AB The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease. C1 UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX 75230. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT DEPT PEDIAT,DIV INFECT DIS,ST LOUIS,MO 63110. ST LOUIS UNIV,SCH MED,DEPT PEDIAT,NIAID,VACCINE EVALUAT UNIT,ST LOUIS,MO 63104. ST LOUIS UNIV,SCH MED,DEPT MED,NIAID,VACCINE EVALUAT UNIT,ST LOUIS,MO 63104. MINNESOTA DEPT HLTH,MINNEAPOLIS,MN. WAYZATA CHILDRENS CLIN,MINNEAPOLIS,MN. CHILDRENS HOSP OAKLAND,RES INST,OAKLAND,CA. FU NIAID NIH HHS [AI-25008, AI-17962, AI-21842] NR 34 TC 96 Z9 96 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 SEP PY 1993 VL 168 IS 3 BP 663 EP 671 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LU337 UT WOS:A1993LU33700018 PM 8354908 ER PT J AU HIBBS, RG CORWIN, AL HASSAN, NF KAMEL, M DARWISH, M EDELMAN, R CONSTANTINE, NT RAO, MR KHALIFA, AS MOKHTAR, S FAM, NS EKLADIOUS, EM BASSILY, SB AF HIBBS, RG CORWIN, AL HASSAN, NF KAMEL, M DARWISH, M EDELMAN, R CONSTANTINE, NT RAO, MR KHALIFA, AS MOKHTAR, S FAM, NS EKLADIOUS, EM BASSILY, SB TI THE EPIDEMIOLOGY OF ANTIBODY TO HEPATITIS-C IN EGYPT SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID HEPATOCELLULAR-CARCINOMA; VIRUS-INFECTION; BLOOD-DONORS; PREVALENCE C1 CAIRO UNIV,FAC MED,CAIRO,EGYPT. AIN SHAMS UNIV,FAC MED,DEPT MICROBIOL,CAIRO,EGYPT. AIN SHAMS UNIV,FAC MED,DEPT PEDIAT,CAIRO,EGYPT. THEODOR BILHARZ RES INST,CAIRO,EGYPT. UNIV MARYLAND,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP HIBBS, RG (reprint author), NAVMEDRSCHU 3,RES PUBLICAT RES,CODE 301B,FPO AE 09835-007,CAIRO,EGYPT. NR 10 TC 41 Z9 43 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 SEP PY 1993 VL 168 IS 3 BP 789 EP 790 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LU337 UT WOS:A1993LU33700046 PM 8394867 ER PT J AU GORDON, M ALEXANDER, PC AF GORDON, M ALEXANDER, PC TI RESEARCH ON TREATMENT OF ADULTS SEXUALLY ABUSED IN CHILDHOOD - INTRODUCTION SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Editorial Material C1 UNIV MARYLAND,COLL PK,MD 20742. RP GORDON, M (reprint author), NIMH,VIOLENCE & TRAUMAT STRESS RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD SEP PY 1993 VL 8 IS 3 BP 307 EP 311 DI 10.1177/088626093008003001 PG 5 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA LQ602 UT WOS:A1993LQ60200001 ER PT J AU FUJIMOTO, W MARVIN, KW GEORGE, MD CELLI, G DARWICHE, N DE LUCA, LM JETTEN, AM AF FUJIMOTO, W MARVIN, KW GEORGE, MD CELLI, G DARWICHE, N DE LUCA, LM JETTEN, AM TI EXPRESSION OF CORNIFIN IN SQUAMOUS DIFFERENTIATING EPITHELIAL TISSUES, INCLUDING PSORIATIC AND RETINOIC ACID-TREATED SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; CHOLESTEROL SULFOTRANSFERASE ACTIVITY; TERMINAL DIFFERENTIATION; CELL-ENVELOPE; MESSENGER-RNA; TRACHEAL EPITHELIUM; HUMAN LORICRIN; INVITRO; INVOLUCRIN AB The expression of cornifin, a putative cross-linked envelope precursor, was investigated in several squamous differentiating tissues by in situ hybridization and immunohistochemical analysis. Cornifin mRNA and protein, which are absent in the normal mucociliary tracheal epithelium, are induced in the suprabasal layers of the squamous metaplastic tracheal epithelium of vitamin A - deficient hamsters. Similar to the induction of squamous metaplasia in vivo, culture of rabbit tracheal cells in the absence of retinoids results in squamous differentiation and expression of cornifin. This induction of cornifin expression is suppressed by retinoic acid and several of its analogs. Cornifin mRNA and protein are also detected in the suprabasal layers of the squamous epithelium of rabbit esophagus and tongue. The distribution of cornifin in human epidermis was compared with that of two other crosslinked envelope precursor proteins, involucrin and loricrin. The localization of cornifin and involucrin is very similar. Both are induced in the spinous layer and appear at an earlier stage during epidermal differentiation than loricrin. The expression of cornifin is greatly increased in psoriatic skin. Cornifin mRNA is barely detectable in normal epidermis, whereas it is present at relatively high levels in the suprabasal layers of psoriatic epidermis. Topical treatment with RA results in thickening of the skin and increases the level of cornifin mRNA and protein in the upper spinous layers of mouse skin. Cornifin expression correlates generally with squamous differentiation in a variety of tissues and is abnormally regulated in psoriatic skin and in skin treated topically with retinoic acid. C1 NIEHS, PULM PATHOBIOL LAB, CELL BIOL SECT, RES TRIANGLE PK, NC 27709 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426; Jetten, Anton/0000-0003-0954-4445 NR 53 TC 49 Z9 49 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1993 VL 101 IS 3 BP 268 EP 274 DI 10.1111/1523-1747.ep12365200 PG 7 WC Dermatology SC Dermatology GA LX786 UT WOS:A1993LX78600006 PM 8370963 ER PT J AU MCNEELY, MC LAWLEY, TJ HARVATH, L AF MCNEELY, MC LAWLEY, TJ HARVATH, L TI MONOCLONAL-ANTIBODY MODULATES HUMAN NEUTROPHIL CHEMOTAXIS TO N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE (FMLP) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; RESPIRATORY BURST; C5A RECEPTOR; ACTIVATION; ANTIGEN; MEMBRANE; PEPTIDES; ADHESION; PROTEINS AB Utilizing standard hybridoma techniques and a neutrophil chemotaxis assay for screening we produced a mouse monoclonal IgM antibody, 59/4, selected for specific inhibition of human neutrophil chemotaxis to the N-formyl-methionyl-leucyl-phenylalanine peptide (fMLP). Antibody 59/4 inhibited neutrophil chemotaxis to FMLP, but not human C5a or leukotriene B4. The antibody exhibited specific homogeneous binding to PMNs, heterogeneous binding to monocytes, and did not bind to lymphocytes in a pattern similar to the profile of N-formyl peptide binding in flow cytometric analysis. The antibody did not inhibit the binding of fluorescein-conjugated fMLPK or fML(H-3)P ligands to neutrophils in flow cytometric or competitive binding assays. Other neutrophil functions including myeloperoxidase release and rosette formation with immunoglobulin or immunoglobulin C3b-coated sheep erythrocytes were not affected in the presence of antibody 59/4. These results suggest that 59/4 specifically inhibits chemotaxis to fMLP. C1 EMORY UNIV,DEPT DERMATOL,ATLANTA,GA 30322. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20014. RP MCNEELY, MC (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1993 VL 101 IS 3 BP 377 EP 382 DI 10.1111/1523-1747.ep12365592 PG 6 WC Dermatology SC Dermatology GA LX786 UT WOS:A1993LX78600025 PM 8396610 ER PT J AU LONDON, RE AF LONDON, RE TI CHEMICAL-SHIFT AND LINEWIDTH CHARACTERISTICS OF REVERSIBLY BOUND LIGANDS SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; EQUILIBRIUM-CONSTANTS; RELAXATION-TIMES; FREE MAGNESIUM; F-19 NMR; EXCHANGE; SYSTEMS; CALCIUM; ATP RP LONDON, RE (reprint author), NIEHS,MOLEC BIOPHYS LAB,MD 17-05,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 16 Z9 16 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD SEP PY 1993 VL 104 IS 2 BP 190 EP 196 DI 10.1006/jmra.1993.1208 PG 7 WC Physics, Atomic, Molecular & Chemical SC Physics GA LY246 UT WOS:A1993LY24600009 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - OB-GYN RESEARCH - SOME SOLUTIONS SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD FAL PY 1993 VL 3 IS 4 BP 211 EP 211 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ML269 UT WOS:A1993ML26900001 ER PT J AU GOZES, I GLOWA, J BRENNEMAN, DE MCCUNE, SK LEE, E WESTPHAL, H AF GOZES, I GLOWA, J BRENNEMAN, DE MCCUNE, SK LEE, E WESTPHAL, H TI LEARNING AND SEXUAL DEFICIENCIES IN TRANSGENIC MICE CARRYING A CHIMERIC VASOACTIVE-INTESTINAL-PEPTIDE GENE SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE VIP; DIPHTHERIA TOXIN, POLYOMA PROMOTER; GENETIC MANIPULATION; VIP TRANSGENIC ANIMALS; LEARNING AND MEMORY, SEXUAL BEHAVIOR ID TOXIN-A-CHAIN; VIP-GENE; POLYPEPTIDE VIP; RAT; ANTAGONIST; EXPRESSION; MOUSE; CELLS; IMPAIRMENT; SEQUENCES AB The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxin-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,LDN,DEV ST MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. RP GOZES, I (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. NR 41 TC 47 Z9 48 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FAL PY 1993 VL 4 IS 3 BP 185 EP 193 DI 10.1007/BF02782501 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MH805 UT WOS:A1993MH80500005 PM 8292491 ER PT J AU CASPI, RR CHAN, CC FUJINO, Y NAJAFIAN, F GROVER, S HANSEN, CT WILDER, RL AF CASPI, RR CHAN, CC FUJINO, Y NAJAFIAN, F GROVER, S HANSEN, CT WILDER, RL TI RECRUITMENT OF ANTIGEN-NONSPECIFIC CELLS PLAYS A PIVOTAL ROLE IN THE PATHOGENESIS OF A T-CELL-MEDIATED ORGAN-SPECIFIC AUTOIMMUNE-DISEASE, EXPERIMENTAL AUTOIMMUNE UVEORETINITIS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; RECRUITMENT; T-CELL LINES; UVEITIS; AUTOIMMUNE DISEASE; INFLAMMATION ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; ATHYMIC NUDE RATS; MULTIPLE-SCLEROSIS; ADOPTIVE TRANSFER; INDUCED ARTHRITIS; LYMPHOCYTES-T; GENE USAGE; S-ANTIGEN AB Experimental autoimmune uveoretinitis (EAU) is a prototypic T cell-mediated autoimmune disease, whose target tissue is the neural retina, that is used as a model for a number of human blinding ocular diseases of a presumed autoimmune nature. EAU in rats can be induced by adoptive transfer of small numbers of retinal antigen-specific CD4+ T cell lines. Although recruitment mechanisms were assumed to play a role in the immunopathogenesis of uveitis, there is no direct evidence that would permit assessment of the importance of recruited non-antigen-specific T cells in retinal autoimmunity. In the present study, we addressed this question by using congenitally athymic Lewis rats (LEW.rnu/rnu), that are deficient in functional endogenous T cells, but are otherwise syngeneic with the euthymic Lewis rats that develop characteristically severe EAU. The uveitogenic stimulus was delivered in the form of phenotypically and functionally homogeneous pathogenic T cell lines, specific to the major pathogenic epitope of either the intracellular photoreceptor protein, S-Ag, or the extracellular photoreceptor matrix protein, IRBP. Depending on the T cell line used, EAU in athymic rats was either drastically reduced in severity (IRBP), or essentially absent (S-Ag). Susceptibility was restored when the athymic animals were reconstituted with immunocompetent T cells from syngeneic euthymic donors. While the intraocular infiltrate in euthymic rats was predominantly lymphocytic, with smaller numbers of monocyte/macrophages and even fewer neutrophils, the sparse infiltrate in athymics was largely monocytic, and with a relatively high proportion of neutrophils and eosinophils. Reconstituted animals had an intermediate histological picture with respect to the infiltrating cell types and disease severity. Our data are consistent with the interpretation that recruitment of naive T cells constitutes an amplification mechanism that is central to the expression and pathogenesis of uveitis. The extent of dependence on this phenomenon appears to be influenced by the antigenic specificity of the T cell line, and could be connected to the 'accessibility' of the target antigen in vivo. C1 NIH,VET RESOURCES BRANCH,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD. RP CASPI, RR (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N222,BETHESDA,MD 20892, USA. NR 39 TC 64 Z9 65 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1993 VL 47 IS 2 BP 177 EP 188 DI 10.1016/0165-5728(93)90028-W PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA LY146 UT WOS:A1993LY14600009 PM 8370769 ER PT J AU ELMALLAKH, RS LI, R AF ELMALLAKH, RS LI, R TI IS THE NA+-K+-ATPASE THE LINK BETWEEN PHOSPHOINOSITIDE METABOLISM AND BIPOLAR DISORDER SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PROTEIN-KINASE-C; CHRONIC LITHIUM TREATMENT; INOSITOL PHOSPHOLIPID HYDROLYSIS; NERVE-CONDUCTION-VELOCITY; INDUCED DIABETIC RATS; INTRACELLULAR CALCIUM-CONCENTRATION; POSITRON EMISSION TOMOGRAPHY; SODIUM-POTASSIUM-ATPASE; PITUITARY-TUMOR CELLS; DIETARY MYOINOSITOL AB Recent experimental work suggests involvement Of the phosphatidyl inositol second messenger system in the biochemical mechanism of lithium action, but this work has not shed light on the pathophysiology of bipolar illness. Earlier work had established reduction in sodium-potassium-activated adenosine triphosphatase (Na+-K+-ATPase) activity as a consistent marker of mood in bipolar illness but had only partially illuminated mechanisms of the action of lithium. Now, advances from research in diabetic neuropathy suggest that inositol phosphate and diacylglycerol metabolism are indeed linked to Na+-K+-ATPase activity. The data are compatible with a model in which a primary decrease in Na+-K+-ATPase activity in bipolar patients can stimulate an increase in phosphoinositide hydrolysis, thereby generating the equivalent of a second messenger signal in the absence of a first message. Lithium appears to act by blocking this false second message. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RP ELMALLAKH, RS (reprint author), UNIV LOUISVILLE,SCH MED,DEPT PSYCHIAT & BEHAV SCI,MOOD DISORDERS RES PROGRAMS,LOUISVILLE,KY 40292, USA. NR 94 TC 29 Z9 30 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1993 VL 5 IS 4 BP 361 EP 368 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MD593 UT WOS:A1993MD59300001 PM 8286932 ER PT J AU GEORGE, MS KETTER, TA GILL, DS HAXBY, JV UNGERLEIDER, LG HERSCOVITCH, P POST, RM AF GEORGE, MS KETTER, TA GILL, DS HAXBY, JV UNGERLEIDER, LG HERSCOVITCH, P POST, RM TI BRAIN-REGIONS INVOLVED IN RECOGNIZING FACIAL EMOTION OR IDENTITY - AN O-15 PET STUDY SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; DEPRESSED-PATIENTS; RIGHT-HEMISPHERE; CINGULATE GYRUS; FACES; MONKEY; DISSOCIATION; NEURONS AB The functional neuroanatomy of emotion recognition is inadequately understood despite well-documented clinical situations where emotion recognition is impaired (aprosodia). Oxygen-15 water positron-emission tomography (PET) was used to study 9 healthy women volunteers during three match-to-sample conditions, each repeated twice: a study task matching facial emotions and control tasks matching spatial positions or facial identity. Results suggest that the higher order functional neural network for recognizing emotion in visual input likely involves the right anterior cingulate and the bilateral inferior frontal gyri. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIH,DEPT NUCL MED,POSITRON EMISS TOMOG SECT,BETHESDA,MD 20892. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 176 Z9 177 U1 6 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1993 VL 5 IS 4 BP 384 EP 394 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MD593 UT WOS:A1993MD59300005 PM 8286936 ER PT J AU NAKAMURA, H GATTASS, R DESIMONE, R UNGERLEIDER, LG AF NAKAMURA, H GATTASS, R DESIMONE, R UNGERLEIDER, LG TI THE MODULAR ORGANIZATION OF PROJECTIONS FROM AREA-V1 AND AREA-V2 TO AREA-V4 AND TEO IN MACAQUES SO JOURNAL OF NEUROSCIENCE LA English DT Article DE VISUAL CORTEX; EXTRASTRIATE CORTEX; STRIATE CORTEX; OCCIPITOTEMPORAL PATHWAY; OBJECT RECOGNITION; COLOR VISION; FORM VISION; MONKEY ID MONKEY VISUAL-CORTEX; INFERIOR TEMPORAL CORTEX; ELECTRON-MICROSCOPIC ANALYSIS; PRIMATE STRIATE CORTEX; OXIDASE-RICH ZONES; CYTOCHROME-OXIDASE; RHESUS-MONKEY; CORTICAL CONNECTIONS; FUNCTIONAL-ANATOMY; SQUIRREL-MONKEY AB In addition to the major anatomical pathways from V1 into the temporal lobe, there are other smaller, ''bypass'' routes that are poorly understood. To investigate the direct projection from V1 to V4 (bypassing V2) and from V2 to TEO (bypassing V4), we injected the foveal and parafoveal representations of V4 and TEO with different retrograde tracers in five hemispheres of four macaques and analyzed the distributions of labeled neurons in V1 and V2 using flattened preparations of the cortex. In V1, labeled neurons were seen after injections in V4 but not TEO. The V4-projecting neurons were located in the foveal representation of V1, in both cytochrome oxidase (CO)-rich blobs and CO-poor interblob regions. In V2, TEO-projecting neurons were intermingled with V4-projecting neurons, although the former were far sparser than the latter. Across the cases, 6-19% of the TEO-projecting neurons were double labeled, that is, also projected to area V4. Both V4- and TEO-projecting neurons formed bands that ran orthogonal to the V1/V2 border, and both were located in CO-rich thin stripes and CO-poor interstripe regions. In some cases, a continuous band of V4-projecting neurons was also found along the V1/V2 border in the foveal representation of V2. The results indicate that the pathways from V1 to V4 and from V2 to TEO involve anatomical subcompartments thought to be concerned with both color and form. These ''bypass'' routes may allow coarse information about color and form to arrive rapidly in the temporal lobe. The bypass route from V2 to TEO might explain the partial sparing of color and form vision that is seen after lesions of V4. By analogy, given the bypass route from the foveal representation of V1 to V4, lesions of V2 affecting the foveal visual field would also be insufficient to block color and form vision. C1 NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892. NR 98 TC 124 Z9 124 U1 2 U2 10 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 SEP PY 1993 VL 13 IS 9 BP 3681 EP 3691 PG 11 WC Neurosciences SC Neurosciences & Neurology GA LW447 UT WOS:A1993LW44700003 PM 7690064 ER PT J AU SCHWARTING, RKW GOLDENBERG, R STEINER, H FORNAGUERA, J HUSTON, JP AF SCHWARTING, RKW GOLDENBERG, R STEINER, H FORNAGUERA, J HUSTON, JP TI A VIDEO IMAGE ANALYZING SYSTEM FOR OPEN-FIELD BEHAVIOR IN THE RAT FOCUSING ON BEHAVIORAL ASYMMETRIES SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE TURNING; CIRCLING; ROTATION; THIGMOTACTIC SCANNING; LOCOMOTION; VIBRISSAE; BASAL GANGLIA; DOPAMINE; 6-HYDROXYDOPAMINE ID SUBSTANTIA-NIGRA; CIRCLING BEHAVIOR; RECORDING ROTATION; BIOGENIC-AMINES; APOMORPHINE; 6-HYDROXYDOPAMINE; DOPAMINE; RECOVERY; HEMIVIBRISSOTOMY; AMPHETAMINE AB A video image analyzing system is presented which measures turning behavior, thigmotactic scanning and locomotion in rats. The system works by analyzing digitized video images obtained by a black/white video camera. Turning behavior is expressed in different diameter classes and as partial or full turns. Thigmotactic scanning is expressed as distance or time locomoted with the left or right side of the body along one of the walls of the testing environment. Locomotion is measured as distance travelled and is expressed in meters. Examples for the application of these behavioral measures are given which include: the measurement of spontaneous or drug-dependent behavioral asymmetries after brain lesion (the unilateral 6-hydroxydopamine model), a unilateral peripheral manipulation (hemivibrissotomy), and the measurement of open-field behavior (spontaneous or drug-induced) in intact animals. Among others, these examples show that the analysis of thigmotactic scanning may provide an alternative behavioral measure, which may be especially useful in the study of functional asymmetries. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP SCHWARTING, RKW (reprint author), HEINRICH HEINE UNIV DUSSELDORF,INST PHYSIOL PSYCHOL I,D-40225 DUSSELDORF,GERMANY. RI Huston, Joseph/C-8986-2009 NR 39 TC 40 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP PY 1993 VL 49 IS 3 BP 199 EP 210 DI 10.1016/0165-0270(93)90125-B PG 12 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ME258 UT WOS:A1993ME25800007 PM 7903729 ER PT J AU RAM, Z CULVER, KW WALBRIDGE, S FRANK, JA BLAESE, RM OLDFIELD, EH AF RAM, Z CULVER, KW WALBRIDGE, S FRANK, JA BLAESE, RM OLDFIELD, EH TI TOXICITY STUDIES OF RETROVIRAL-MEDIATED GENE-TRANSFER FOR THE TREATMENT OF BRAIN-TUMORS SO JOURNAL OF NEUROSURGERY LA English DT Article DE RETROVIRAL VECTOR; GENE TRANSFER; BRAIN NEOPLASM; GANCICLOVIR; THYMIDINE KINASE; TOXICITY; MOUSE; RAT; PRIMATE ID THYMIDINE KINASE GENES; CELLS; INVIVO AB Retroviral-mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene into malignant tumors confers drug susceptibility to the antiviral drug ganciclovir. The authors have recently shown that in situ transduction of the rat 9L brain tumor following HSVtk-producer cell implantation led to tumor regression after ganciclovir administration in treated rats. A wide spectrum of potential adverse effects may, however, be associated with the application of this approach to treat brain tumors, including dissemination of the retroviral vector to nontumoral tissues within or outside the central nervous system, proliferation of the injected murine vector-producer cells at the injection site, immune-mediated responses to the implantation of xenogeneic cells, and damage to the brain from toxic by-products of the HSVtk-ganciclovir interaction. These possibilities were investigated using intracerebral and systemic injections of retroviral vector-producer cells carrying the HSVtk or the lacZ gene in mice, rats, and nonhuman primates. Using the lacZ gene as a reporter gene, no evidence of beta-galactosidase activity consistent with vector transduction was detected in any major body organ in the treated mice or rats. Similarly, the HSVtk gene transfer did not result in toxicity, with or without ganciclovir administration. In studies using rat and monkey models, no proliferation of the vector-producer cells occurred after intracerebral injection. Vector-producer cell survival was limited to 7 to 14 days. High-dose steroid therapy did not appear to extend the survival of these xenogeneic cells in rats. No significant inflammatory response was observed in the meninges or brain parenchyma. Endothelial cells were occasionally transduced in brain capillaries adjacent to the injected site of the vector-producer cells. Injection of producer cells into brain tissue elicited mild edema and reactive gliosis surrounding the injection site, which were probably the cause of a transient toxic response arising 4 to 5 days following injection of the producer cells; short-term administration of dexamethasone eliminated that response. No neurological deficits were observed in the rats or primates treated with the HSVtk vector-producer cells, with or without ganciclovir. In primates injected with producer cells, magnetic resonance imaging before, during, and after ganciclovir administration showed minimal and localized breakdown of the blood-brain barrier without significant edema or mass effect. Similarly, histological examination of the monkeys' brains showed no damage to neurons, astroglia, or myelin. Long-term clinical (> 9 months) and radiological (3 months) assessment of the primates has revealed no evidence of toxicity. The results of these studies indicate that intra-tumoral implantation of HSVtk-producer cells can be attempted for the treatment of brain tumors, without anticipating significant adverse toxicity to normal brain or remote proliferating tissues. C1 NCI,DIAGNOST RADIOL RES PROGRAM,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RP RAM, Z (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,ROOM 5D37,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 97 Z9 98 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 SEP PY 1993 VL 79 IS 3 BP 400 EP 407 DI 10.3171/jns.1993.79.3.0400 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LU690 UT WOS:A1993LU69000014 PM 8395592 ER PT J AU VANOSDOL, WW SUNG, C DEDRICK, RL WEINSTEIN, JN AF VANOSDOL, WW SUNG, C DEDRICK, RL WEINSTEIN, JN TI A DISTRIBUTED PHARMACOKINETIC MODEL OF 2-STEP IMAGING AND TREATMENT PROTOCOLS - APPLICATION TO STREPTAVIDIN-CONJUGATED MONOCLONAL-ANTIBODIES AND RADIOLABELED BIOTIN SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID BINDING-SITE BARRIER; HUMAN-MELANOMA XENOGRAFTS; SOLID TUMORS; PERIVASCULAR DISTRIBUTION; INTERSTITIAL PRESSURE; NEOPLASTIC TISSUES; MACROMOLECULES; TRANSPORT; AFFINITY; HAPTENS AB Two-step imaging and treatment protocols involve injecting a suitably prepared monoclonal antibody that can bind both to a specific tumor antigen and to a second reagent which carries a drug or radionuclide. The second component is injected later, after the antibody has distributed throughout the target tumors and been largely cleared from the plasma and normal tissues. We introduce a mathematical model for the analysis of such protocols and apply it to the case of a streptavidinylated monoclonal antibody and radiolabeled biotin diffusing into small, prevascular, densely cellular nodules that represent either primary or metastatic tumors. We examine the distribution of streptavidinylated antibody and radiolabeled biotin within a tumor nodule and compare the two-step protocol to a one-step protocol using radiolabeled antibody. Our analysis predicts that (1) streptavidinylation reduces both the amount of antibody that distributes into the tumor nodule and the homogeneity of that distribution; (2) streptavidinylated antibody in the nodule can be saturated by initial plasma concentrations of free radiolabeled biotin substantially lower than the initial plasma concentration of free streptavidinylated antibody; (3) radiolabeled biotin diffuses rapidly, but binds so quickly that it will not penetrate deeply into the nodule if too low a dose is given. Hence, nonuniform localization of radiolabel may result f rom a ''binding site barrier to diffusion of either or both components; and (4) the two-step protocol permits imaging sooner after injection of radiolabeled material than the one-step protocol and produces a higher exposure in tumor relative to plasma, even in the presence of antigen turnover. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 37,BETHESDA,MD 20892. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 53 TC 47 Z9 49 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1993 VL 34 IS 9 BP 1552 EP 1564 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LU701 UT WOS:A1993LU70100032 PM 8355076 ER PT J AU OPARA, EC HUBBARD, VS AF OPARA, EC HUBBARD, VS TI ESSENTIAL FATTY-ACIDS (EFA) - ROLE IN PANCREATIC HORMONE-RELEASE AND CONCOMITANT METABOLIC EFFECT SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE LINOLEIC ACID; LINOLENIC ACID; METABOLISM; INSULIN; GLUCAGON; PARENTERAL NUTRITION ID PROTEIN-KINASE-C; TOTAL PARENTERAL-NUTRITION; INDUCED INSULIN-SECRETION; SENSITIVE K+ CHANNELS; ARACHIDONIC-ACID; CYSTIC-FIBROSIS; RAT ISLETS; LINOLEIC-ACID; BETA-CELLS; B-CELLS AB Certain fatty acids have been identified as essential fatty acids (EFA) because they cannot be made by mammalian tissues and have to be obtained from plant and marine dietary sources. These fatty acids are the polyunsaturated fatty acids (PUFA), linoleic acid (18:2, omega 6), and linolenic acid (18.3, omega 3). Apart from the fact that they can be elongated and desaturated to yield bioactive molecules with longer chains and higher double bonds such as arachidonic acid (from linoleate) and eicosanoids (from both fatty acids), they are very easily oxidized in the presence of oxygen to provide metabolic energy. Recent studies have also shown that PUFA are potent insulin secretagogues. In this review article, an attempt has been made to evaluate these new data and to discuss their potential usefulness in nutritional support. C1 NIDDKD,NUTR SCI BRANCH,WESTWOOD BLDG,ROOM 3A18,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,SARA W STEDMAN CTR NUTR STUDIES,DURHAM,NC 27710. NR 102 TC 15 Z9 15 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 1993 VL 4 IS 9 BP 498 EP 509 DI 10.1016/0955-2863(93)90085-B PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA LV477 UT WOS:A1993LV47700001 ER PT J AU TAKAHASHI, Y AUGUSTIN, W WYMAN, M KADOR, PF AF TAKAHASHI, Y AUGUSTIN, W WYMAN, M KADOR, PF TI QUANTITATIVE-ANALYSIS OF RETINAL VESSEL CHANGES IN GALACTOSE-FED DOGS SO JOURNAL OF OCULAR PHARMACOLOGY LA English DT Article AB Retinal vessel changes in 36-month 30% galactose-fed beagles treated with or without aldose reductase inhibitors were quantified using an Olympus Cue-3 color image analysis system. Individual maps of the intact retinal vasculature, isolated by trypsin-digestion, were divided into 24 distinct subregions and measurements of either the endothelial cell to pericyte (E/P) ratio or cell densities, expressed as pericytes per mm capillary length or endothelial cells per mm capillary length, were conducted in 0.1 mm2 areas surrounding the midpoints of 12 subregions associated with the highest incidence of microaneurysms. Significantly increased E/P ratios and decreased pericyte densities were observed with the duration of galactose-feeding. These retinal changes were reduced by aldose reductase inhibitor treatment. Correlations between the E/P ratio and either number of microaneurysms or cataract severity were also observed. These data support the dose-dependent effects of aldose reductase inhibitors in preventing pericyte degeneration and subsequent formation of microaneurysms (Archives Ophthalmol. 108:1301, 1990). C1 NEI,BLDG 10,ROOM 10B11,BETHESDA,MD 20892. NR 0 TC 18 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 8756-3320 J9 J OCUL PHARMACOL PD FAL PY 1993 VL 9 IS 3 BP 257 EP 269 DI 10.1089/jop.1993.9.257 PG 13 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA LY174 UT WOS:A1993LY17400006 PM 8228533 ER PT J AU HILLMAN, LS JOHNSON, LS LEE, DZ VIEIRA, NE YERGEY, AL AF HILLMAN, LS JOHNSON, LS LEE, DZ VIEIRA, NE YERGEY, AL TI MEASUREMENT OF TRUE ABSORPTION, ENDOGENOUS FECAL EXCRETION, URINARY-EXCRETION, AND RETENTION OF CALCIUM IN TERM INFANTS BY USING A DUAL-TRACER, STABLE-ISOTOPE METHOD SO JOURNAL OF PEDIATRICS LA English DT Article ID BIRTH-WEIGHT INFANTS; FED HUMAN-MILK; PREMATURE-INFANTS; MINERAL HOMEOSTASIS; SERUM 25-HYDROXYVITAMIN-D; BONE MINERALIZATION; VITAMIN-D; PHOSPHORUS; METABOLISM; FORMULA AB A dual-tracer, stable-isotope method was used to measure the percentage of true calcium absorption (a), true calcium absorption rate (V(a)), endogenous fecal calcium excretion rate (V(f)), urinary calcium excretion rate (V(u)), and calcium retention rate (V(ra)). Twenty-seven infants with a mean gestation of 30.6 +/- 1.7 weeks and a mean birth weight of 1.4 +/- 0.21 kg were studied at 2 or 3 weeks of age, or both, during feedings of human milk (HM), fortified human milk (HMF), and commercially available formula (20 or 24 calories per ounce) for premature infants (EPF-20/780 and EPF-24/940) (part 1 of our study). Of 13 additional infants with a mean (+/- SD) birth weight of 1.26 +/- 0.25 kg and gestation of 29.6 +/- 2.5 weeks, 11 completed a crossover-design study at 2 and 3 weeks of age, receiving two identical formulas containing calcium, 940 mg/L, and phosphorus, 470 mg/L (EPF-24/940 formula) or calcium 1340 mg/L, and phosphorus, 680 mg/L (EPF-24/1340 formula) (port 2 of our study). The alpha value was higher in infants receiving HM (76.4 +/- 15.1%) or HMF (68.0 +/- 7.8%) than in those receiving EPF-20/750 formula (54.1% +/- 5.6%) or in previously reported infants fed standard formula (47.1% +/- 11.5%); those given EPF-24/940 formula had intermediate values (63.9% +/- 13.9%, part 1; 56.1% +/- 16.5%, part 2). No significant differences existed among groups for either V(u) or V(f) per kilogram. In the crossover study (part 2), no significant differences were seen between formulas for alpha and for V(a), V(f), or V(ra) per kilogram. However, V(u) per kilogram was significantly decreased in infants receiving the higher mineral formula (EPF-24/940: 3.6 +/- 2.3; EPF-24/1340: 2.9 +/- 2.3 mg/kg per day; p = <0.005). With all feedings, alpha, V(u) per kilogram, and V(f) per kilogram were not related to gestational age, age at study, calcium intake, or each other. However, V(f) per kilogram was inversely related to birth weight. Thus, alpha, V(u), and V(f) appear to be independent and may be differentially affected by factors altering calcium dynamics. We conclude that increasing formula mineral content does not ensure increased retention; careful monitoring of individual infants remains indicated. C1 NATL INST CHILD HLTH & HUMAN DEV, BETHESDA, MD USA. RP HILLMAN, LS (reprint author), UNIV MISSOURI, SCH MED, DEPT CHILD HLTH, 1 HOSP DR, COLUMBIA, MO 65212 USA. FU NICHD NIH HHS [2-R01-HD-23770] NR 32 TC 15 Z9 15 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1993 VL 123 IS 3 BP 444 EP 456 DI 10.1016/S0022-3476(05)81755-X PG 13 WC Pediatrics SC Pediatrics GA LW160 UT WOS:A1993LW16000021 PM 8355125 ER PT J AU WAALKES, MP DIWAN, BA WEGHORST, CM WARD, JM RICE, JM CHERIAN, MG GOYER, RA AF WAALKES, MP DIWAN, BA WEGHORST, CM WARD, JM RICE, JM CHERIAN, MG GOYER, RA TI FURTHER EVIDENCE OF THE TUMOR-SUPPRESSIVE EFFECTS OF CADMIUM IN THE B6C3F1 MOUSE-LIVER AND LUNG - LATE-STAGE VULNERABILITY OF TUMORS TO CADMIUM AND THE ROLE OF METALLOTHIONEIN SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; IMMUNOHISTOCHEMICAL LOCALIZATION; GENE-EXPRESSION; INJECTION SITE; MICE; TOXICITY; CARCINOGENICITY; METALS; RESISTANCE AB Previously, we studied the ability of cadmium to initiate or promote tumors in B6C3F1 mice and, contrary to expectation, found that cadmium inhibited development of N-nitrosodiethylamine (NDEA)-initiated and sodium barbital-promoted liver tumors. In this study, the time course of cadmium inhibition of NDEA-initiated tumor formation was studied. A single dose of NDEA (90 mg/kg i.p.) was given at 5 weeks of age (time 0) followed by cadmium (1 000 ppm) in drinking water from 2 to 48, 4 to 48, 8 to 48, 16 to 48 and 32 to 48 weeks. The study ended at 48 weeks. NDEA-induced elevations in liver tumor incidence (22 tumor-bearing mice/25 total) over control (5/25) were prevented by cadmium regardless of the period of administration (NDEA + cadmium: 2-48 weeks, 2/25; 4-48 weeks, 1/25; 8-48 weeks, 1/25; 16-48 weeks, 2/25; 32-48 weeks, 6/24). Cadmium alone (2-48 weeks) eliminated (0/25) spontaneously occurring liver tumors (5/25). NDEA-induced lung tumor incidence (25/25) and multiplicity (7.28 tumors/lung) were also reduced by cadmium (maximal decreases 28% and 80%, respectively). Some evidence of a specific deficiency of metallothionein in tumor cells was seen immunohistologically in NDEA-induced hepatic lesions and pulmonary lesions. These results indicate that cadmium prevents or reduces tumor formation in the B6C3F1 mouse liver and lung regardless of the exposure interval and apparently by cell-specific cytotoxicity. Auxiliary studies indicated that in mice bearing multiple liver foci resulting from NDEA treatment there was a marked reduction in basal metallothionein levels and in response to zinc induction. The possibility exists that cadmium has a specific toxicity toward previously initiated cells within mouse liver and lung. The mechanisms involved in cadmium-induced tumor suppression deserve further study. C1 UNIV WESTERN ONTARIO,DEPT PATHOL,LONDON N6A 3K7,ONTARIO,CANADA. FCRDC,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP WAALKES, MP (reprint author), NCI,FCRDC,CHIEF INORGAN CARCINOGENESIS SECT,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 58 TC 27 Z9 27 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1993 VL 266 IS 3 BP 1656 EP 1663 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LX772 UT WOS:A1993LX77200064 PM 8371163 ER PT J AU COHEN, LA HOROWITZ, AM AF COHEN, LA HOROWITZ, AM TI COMMUNITY-BASED SEALANT PROGRAMS IN THE UNITED-STATES - RESULTS OF A SURVEY SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE SEALANTS; COMMUNITY PROGRAMS; PREVENTION AB The appropriate use of pit and fissure sealants could reduce substantially the majority of occlusal caries among US school-aged children. The 1986-87 national oral health survey conducted by the NIDR showed that less than B percent of the children 5-17 years of age had sealants on their teeth. The purpose of this national study was to document the current status of community-based sealant programs and to identify general program characteristics. Data were gathered through a mail survey to all state dental directors and site visits to four selected comprehensive community-based programs. Twentynine states were currently conducting sealant programs. The vast majority of these programs had formal quality assurance systems and companion health education components. Eight states indicated that sealant programs had been terminated within the last two years. Medicaid reimbursement for sealants was available in 42 states, with a mean reimbursement rate of $10.71 per sealant. Reimbursement rates ranged from $3.00-$20.00 per sealant. State practice acts almost uniformly permitted the placement of sealants by dental hygienists (n=48), but less frequently by dental assistants (n=15). Approximately 43 percent of state practice acts did not require a dentist to be present physically when auxiliaries place sealants in public/community sealant programs. All respondents indicated that there was a need for additional programs in their state. No structural factors-for example, level of Medicaid reimbursement for sealants or state practice act requirements for auxiliary supervision-were found to be associated with the presence of community-based sealant programs. Nationally, only a small percentage of children appeared fo be receiving sealants in community programs. C1 NIDR,BETHESDA,MD 20892. RP COHEN, LA (reprint author), UNIV MARYLAND,BALTIMORE COLL DENT SURG,SCH DENT,DEPT ORAL HLTH CARE DELIVERY,BALTIMORE,MD 21201, USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1993 VL 53 IS 4 BP 241 EP 245 DI 10.1111/j.1752-7325.1993.tb02711.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA MD983 UT WOS:A1993MD98300007 PM 8258787 ER PT J AU MIYASHITA, Y MILLER, M YEN, PM HARMON, JM HANOVER, JA SIMONS, SS AF MIYASHITA, Y MILLER, M YEN, PM HARMON, JM HANOVER, JA SIMONS, SS TI GLUCOCORTICOID RECEPTOR-BINDING TO RAT-LIVER NUCLEI OCCURS WITHOUT NUCLEAR TRANSPORT SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID CELL-FREE SYSTEM; LARGE-T-ANTIGEN; STEROID COMPLEXES; DEXAMETHASONE 21-MESYLATE; AURINTRICARBOXYLIC ACID; PROGESTERONE-RECEPTOR; MONOCLONAL-ANTIBODIES; LOCALIZATION SIGNAL; HORMONE RECEPTORS; PROTEIN IMPORT AB The binding of cell-free activated glucocorticoid receptor-steroid complexes from HTC cells to various preparations of HTC and rat liver nuclei has been examined under conditions that did or did not support the nuclear translocation of macromolecules via nuclear pores. To the best of our knowledge, this is the first such study with functionally active isolated nuclei. Conventionally prepared HTC nuclei were found to be porous, as determined from their inability to exclude the fluorescent macromolecule phycoerythrin (PE) at 4-degrees-C. Thus the nuclear binding of activated complexes to these nuclei can not involve nuclear translocation. Further studies, using established conditions with sealed nuclei prepared from rat liver, revealed that nuclear translocation of PE containing a covalently linked, authentic nuclear translocation sequence could be obtained at 22-degrees-C, but not at 4-degrees-C. However, under the same conditions, activated glucocorticoid complexes displayed equal levels of nuclear binding at both temperatures. We therefore conclude. that the current translocation conditions with intact rat liver nuclei are not sufficient to reproduce the nuclear transport of glucocorticoid complexes observed in intact cells. The nuclear binding that was seen with intact rat liver nuclei was not affected by aurintricarboxylic acid, which selectively inhibits protein-nucleic acid interactions. The antibody AP-64, shown to be specific for amino acids 506-514 of the nuclear translocation sequence of the rat glucocorticoid receptor, inhibited the nuclear binding of activated complexes, apparently by blocking receptor access to the nuclear membrane. Collectively, these data argue that activated complex binding to nuclei capable of nuclear translocation involves only an association with nuclear membrane components such as nuclear pores. Thus this system, and these reagents, may be useful in future studies of activated complex binding to nuclear pores. C1 NIDDK,LMCB,STEROID HORMONES SECT,BLDG 8,RM B2A-07,BETHESDA,MD 20817. NIDDK,LBM,CELL BIOCHEM SECT,BETHESDA,MD 20817. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. FU NCI NIH HHS [CA-32226] NR 61 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD SEP PY 1993 VL 46 IS 3 BP 309 EP 320 DI 10.1016/0960-0760(93)90220-Q PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LY881 UT WOS:A1993LY88100005 PM 9831479 ER PT J AU SALEM, RR WOLF, BC SEARS, HF LAVIN, PT RAVIKUMAR, TS DECOSTE, D DEMILIA, JC HERLYN, M SCHLOM, J GOTTLIEB, LS STEELE, GD AF SALEM, RR WOLF, BC SEARS, HF LAVIN, PT RAVIKUMAR, TS DECOSTE, D DEMILIA, JC HERLYN, M SCHLOM, J GOTTLIEB, LS STEELE, GD TI EXPRESSION OF COLORECTAL CARCINOMA-ASSOCIATED ANTIGENS IN COLONIC POLYPS SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY B72.3; BLOOD-GROUP ANTIGENS; CARCINOEMBRYONIC ANTIGEN; TISSUES; LEWISX; FETAL; LEA C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,MALLORY INST PATHOL,DEPT PATHOL & LAB MED,BOSTON,MA 02215. RP SALEM, RR (reprint author), HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT SURG,CANC BIOL LAB,BOSTON,MA 02138, USA. FU NCI NIH HHS [CA-44704-02] NR 29 TC 19 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 1993 VL 55 IS 3 BP 249 EP 255 DI 10.1006/jsre.1993.1136 PG 7 WC Surgery SC Surgery GA MB509 UT WOS:A1993MB50900001 PM 8412106 ER PT J AU QUYYUMI, AA DIODATI, JG LAKATOS, E BONOW, RO EPSTEIN, SE AF QUYYUMI, AA DIODATI, JG LAKATOS, E BONOW, RO EPSTEIN, SE TI ANGIOGENIC EFFECTS OF LOW-MOLECULAR-WEIGHT HEPARIN IN PATIENTS WITH STABLE CORONARY-ARTERY DISEASE - A PILOT-STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HUMAN-ENDOTHELIAL CELLS; ANGINA-PECTORIS; MYOCARDIAL-ISCHEMIA; COLLATERAL VESSELS; SEGMENT DEPRESSION; CANINE MODEL; EXERCISE; THROMBOSIS; OCCLUSION AB Objectives. The study was designed to assess the feasibility of conducting a trial to investigate whether exercise and low molecular weight heparin therapy with dalteparin sodium (Fragmin) would improve collateral function to the ischemic myocardium in patients with coronary artery disease. Background. The severity of myocardial ischemia in patients with coronary artery disease is at least partly dependent on the status of the collateral circulation. Therefore, improvement in collateral function would potentially provide a unique way of alleviating myocardial ischemia. Because the combination of ischemia and heparin has previously been demonstrated to enhance collateral growth, we studied the anti-ischemic effects of combined treatment with dalteparin sodium and exercise-induced ischemia in patients with coronary artery disease. Methods. Twenty-three patients with stable coronary artery disease were randomized to receive either subcutaneous dalteparin sodium or placebo for a 4-week period. Patients received either placebo or 10,000 IU of dalteparin sodium by subcutaneous injection once daily for weeks 1 and 2 and 5,000 IU daily for weeks 3 and 4. During the 1st 2 weeks, patients were exercised to ischemia three times a day. At baseline and 4 weeks after treatment, treadmill exercise testing, exercise radionuclide ventriculography and 48-h ambulatory ST segment monitoring were performed. Results. Eight (80%) of the 10 dalteparin sodium-treated patients compared with 4 (31%) of 13 placebo-treated patients (p < 0.02) had an increased rate-pressure product at the onset of 1 mm of ST segment depression. The duration of exercise to ischemia increased in all patients treated with low molecular weight heparin and in 62% of placebo-treated patients (p < 0.03). The number and duration of episodes of ST segment depression during ambulatory monitoring decreased by 30% and 35%, respectively (p < 0.05), in the dalteparin sodium group but were unchanged in the placebo group. The decrease in left ventricular ejection fraction with exercise was lower in 80% of dalteparin sodium-treated patients compared with 54% of placebo-treated patients (p = 0.06). When all five factors reflecting collateral function were considered together in a multivariate analysis of variance, there was a significant improvement in low molecular weight heparin-treated patients compared with placebo-treated patients (p = 0.014). Conclusions. This study provides preliminary evidence suggesting that exercise and low molecular weight heparin therapy with dalteparin sodium lessen myocardial ischemia and that the improvement is likely to be mediated by enhanced collateral function. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 36 TC 44 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1993 VL 22 IS 3 BP 635 EP 641 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MQ361 UT WOS:A1993MQ36100001 PM 8394849 ER PT J AU DILSIZIAN, V BONOW, RO EPSTEIN, SE FANANAPAZIR, L AF DILSIZIAN, V BONOW, RO EPSTEIN, SE FANANAPAZIR, L TI MYOCARDIAL-ISCHEMIA DETECTED BY THALLIUM SCINTIGRAPHY IS FREQUENTLY RELATED TO CARDIAC-ARREST AND SYNCOPE IN YOUNG-PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; NORMAL CORONARY-ARTERIES; PERFUSION ABNORMALITIES; ANGINA-PECTORIS; SUDDEN-DEATH; EXERCISE; VERAPAMIL; RESERVE; ARRHYTHMIA; PROGNOSIS AB Objectives. The purpose of this study was to determine the frequency of myocardial ischemia as a potential mechanism for cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy who experienced such complications. Background. Sudden cardiac death and syncope occur frequently inpatients with hypertrophic cardiomyopathy. Although ventricular arrhythmias account for most of these events in adult patients, the mechanism responsible for cardiac arrest and syncope in young patients has not been established. Methods. Twenty-three patients with hypertrophic cardiomyopathy, aged 6 to 23 years, with previous cardiac arrest (n = 8), syncope (n = 7) or a family history of sudden cardiac death (n = 8) were evaluated to determine the prevalence of spontaneous ambulatory ventricular tachycardia (24- to 72-h electrocardiographic [ECG] monitoring), exercise-induced myocardial ischemia (thallium scintigraphy) and inducibility of ventricular tachycardia (electrophysiologic studies). Results. Three of 15 patients with a history of cardiac arrest or syncope had ventricular tachycardia on ambulatory ECG monitoring. However, all 15 patients, had inducible ischemia by thallium scintigraphy compared with only 3 (37%) of 8 patients with no such history (p < 0.01). In contrast, ventricular tachycardia induction was uncommon in all of the young patients (27% in those with cardiac arrest or syncope; 0% in the others). During therapy for ischemia with verapamil alone or in combination with beta-adrenergic blocking agents, only 4 of the 15 patients with cardiac arrest or syncope had further episodes. In three of the four patients, these events were temporally related to discontinuation of verapamil. Among eight patients who had a repeat exercise thallium study while receiving anti-ischemic therapy, seven (88%) had improved regional thallium uptake, of whom three had normal thallium studies. Conclusions. These data suggest that in young patients with hypertrophic cardiomyopathy, sudden cardiac arrest or syncope is frequently related to ischemia rather than to a primary arrhythmogenic ventricular substrate. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP DILSIZIAN, V (reprint author), NIH,DEPT NUCL MED,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 34 TC 166 Z9 175 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1993 VL 22 IS 3 BP 796 EP 804 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MQ361 UT WOS:A1993MQ36100025 PM 8102625 ER PT J AU JONES, RB POMREHN, PR MECKLENBURG, RE LINDSAY, EA MANLEY, M OCKENE, JK AF JONES, RB POMREHN, PR MECKLENBURG, RE LINDSAY, EA MANLEY, M OCKENE, JK TI THE COMMIT DENTAL MODEL - TOBACCO CONTROL PRACTICES AND ATTITUDES SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB The National Cancer institute's program to help dentists reduce tobacco use among their patients is part of the Community Intervention Trial for Smoking Cessation, a 22-community, randomly controlled trial of an intervention program for smoking cessation. Results of COMMIT baseline surveys Of dentists in the 11 intervention communities are presented. C1 UNIV IOWA,COLL MED,IOWA CITY,IA 52242. NCI,PUBL HLTH APPLICAT RES BRANCH,BETHESDA,MD 20892. RP JONES, RB (reprint author), UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242, USA. NR 5 TC 25 Z9 25 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 1993 VL 124 IS 9 BP 92 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LX288 UT WOS:A1993LX28800020 PM 8409033 ER PT J AU BRESLOW, RA SORKIN, JD AF BRESLOW, RA SORKIN, JD TI COMPARISON OF ONE-DAY AND 3-DAY CALORIE COUNTS IN HOSPITALIZED-PATIENTS - A PILOT-STUDY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NURSING-HOME MEN; NUTRITIONAL ASSESSMENT; MORTALITY; DEATH AB Objective: To determine whether a 1-day calorie count can replace the labor-intensive 3-day calorie count commonly performed in hospitalized patients when estimates of caloric and protein intake are required. Design: Pilot study using prospective, non-concurrent review of medical records. Setting: Hospital. Participants: Thirty patients (mean age 67 years). Results: Mean 3-day intake (952 +/- 91 calories, 41 +/- 4 g protein) was about half of calculated requirements; first-day intake was similar (918 +/- 116 calories, 40 +/- 5 g protein). The first day had high sensitivity (calories 96%; protein 93%) and positive predictive value (calories 100%; protein 96%). Malnutrition was evident; three-fourths of patients had weights below recommended ranges, and 83% were hypoalbuminemic. Conclusions: Three-day calorie counts are frequently performed in patients suspected of eating poorly. Results of this pilot study suggest that 1-day calorie counts may be a valid alternative. However, readily available anthropometric and biochemical data may be as good an indicator of inadequate dietary intake. C1 WESTAT CORP,ROCKVILLE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 17 TC 8 Z9 8 U1 0 U2 2 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 SEP PY 1993 VL 41 IS 9 BP 923 EP 927 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LW378 UT WOS:A1993LW37800004 PM 8409178 ER PT J AU SHAW, GL SRIVASTAVA, S AF SHAW, GL SRIVASTAVA, S TI MEETING HIGHLIGHTS - NATIONAL-CANCER-INSTITUTE WORKSHOP ON EARLY DETECTION OF CANCER - CHALLENGES FOR MOLECULAR-BIOLOGY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID C-ERBB-2 ONCOGENE; MUTATIONS; GENETICS; INSITU; BREAST; LUNG C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. NR 13 TC 3 Z9 3 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 SEP 1 PY 1993 VL 85 IS 17 BP 1377 EP 1381 DI 10.1093/jnci/85.17.1377 PG 5 WC Oncology SC Oncology GA LU580 UT WOS:A1993LU58000011 PM 8102407 ER PT J AU SANDLER, AB VANDEPOL, SB SPALHOLZ, BA AF SANDLER, AB VANDEPOL, SB SPALHOLZ, BA TI REPRESSION OF BOVINE PAPILLOMAVIRUS TYPE-1 TRANSCRIPTION BY THE E1 REPLICATION PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSFORMING REGION; DNA-BINDING; CONSTITUTIVE ENHANCER; SIMIAN VIRUS-40; GENE-EXPRESSION; TERMINAL DOMAIN; MESSENGER-RNAS; C127 CELLS; E2; ACTIVATION AB Bovine papillomavirus type 1 (BPV-1) is the prototype virus for the study of papillomavirus gene regulation. The functions of the BPV-1 E2 proteins in transcriptional regulation have been well characterized. The BPV-1 El protein is required for viral DNA replication and can bind to the origin of replication alone or in a complex with the E2 transactivator protein. In this study, we demonstrated that the BPV-1 El protein is also involved in transcriptional regulation. The El protein significantly repressed E2-transactivated transcription from the major early promoter P89. This activity is consistent with the elevated level of P89 transcription observed in BPV-1 El open reading frame mutants. Transcriptional repression by El correlated with the ability of an E1-E2 protein complex to bind the replication origin but was not dependent on viral DNA replication. These studies identify a new mechanism involved in the regulation of papillomavirus transcription which has implications regarding expression of the viral transforming functions. RP SANDLER, AB (reprint author), NCI,TUMOR VIRUS BIOL LAB,BLDG 41,ROOM D505,BETHESDA,MD 20892, USA. NR 61 TC 42 Z9 44 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 SEP PY 1993 VL 67 IS 9 BP 5079 EP 5087 PG 9 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700001 PM 8394436 ER PT J AU ROULSTON, A BEAUPARLANT, P RICE, N HISCOTT, J AF ROULSTON, A BEAUPARLANT, P RICE, N HISCOTT, J TI CHRONIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION STIMULATES DISTINCT NF-KAPPA-B/REL DNA-BINDING ACTIVITIES IN MYELOMONOBLASTIC CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTOONCOGENE BCL-3 ENCODES; GENE-EXPRESSION; P65 SUBUNIT; TRANSCRIPTIONAL ACTIVATION; NUCLEAR FACTOR; 65-KD SUBUNIT; U937 CELLS; MONOCYTE DIFFERENTIATION; MONONUCLEAR PHAGOCYTES AB The relationship between human immunodeficiency virus type 1 (HIV-1) infection and the induction of NF-KB binding activity was examined in a myeloid cell model of HIV-1 infection derived from the PLB-985 cell line. Chronic infection of PLB-985 cells led to increased monocyte-specific surface marker expression, increased c-fms gene transcription, and morphological alterations consistent with differentiation along the monocytic pathway. PLB-IIIB cells displayed a constitutive NF-kappaB-like binding activity that was distinct from that induced by tumor necrosis factor alpha or phorbol 12-myristate 13-acetate treatment of the parental PLB-985 cell line. This unique DNA binding activity consisted of proteins of 70, 90, and 100 kDa with a high degree of binding specificity for the NF-kappaB site within the PRDII domain of beta interferon. In this report, we characterize the nature of these proteins and demonstrate that binding of these proteins is also induced following Sendai paramyxovirus infection. The 70-kDa protein corresponds to the NF-kappaB RelA (p65) subunit, which is activated in response to an acute paramyxovirus infection or a chronic HIV-1 infection. Virus infection does not appear to alter the amount of RelA (p65) or NFKB1 (p50) but rather affects the capacity of IkappaBalpha to sequester RelA (p65), therefore leading to constitutive levels of RelA DNA binding activity and to increased levels of NF-kappaB-dependent gene activity. The virally induced 90- to 100-kDa proteins have a distinct binding specificity for the PRDII domain and an AT-rich sequence but do not cross-react with NF-kappaB subunit-specific antisera directed against NFKB1 (p105 or p50), NFKB2 (p100 or p52), RelA (p65), or c-rel. DNA binding of the 90- to 100-kDa proteins was not inhibited by recombinant IkappaBalpha/MAD-3 and was resistant to tryptic digestion, suggesting that these proteins may not be NF-kappaB related. Transient cotransfection experiments demonstrated that RelA and NFKB1 expression maximally stimulated HIV-1 LTR- and NF-KB-dependent reporter genes; differences in NF-kappaB-like binding activity were also reflected in higher constitutive levels of NF-kappaB-regulated gene expression in HIV-1-infected myeloid cells. C1 MCGILL UNIV,SIR MORTIMER B DAVIS JEWISH GEN HOSP,LADY DAVIS INST MED RES,MONTREAL H3T 1E2,PQ,CANADA. MCGILL UNIV,DEPT MICROBIOL & IMMUNOL,MONTREAL H3T 1E2,PQ,CANADA. FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 74 TC 49 Z9 49 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 SEP PY 1993 VL 67 IS 9 BP 5235 EP 5246 PG 12 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700017 PM 8394446 ER PT J AU COHEN, BD GOLDSTEIN, DJ RUTLEDGE, L VASS, WC LOWY, DR SCHLEGEL, R SCHILLER, JT AF COHEN, BD GOLDSTEIN, DJ RUTLEDGE, L VASS, WC LOWY, DR SCHLEGEL, R SCHILLER, JT TI TRANSFORMATION-SPECIFIC INTERACTION OF THE BOVINE PAPILLOMAVIRUS E5 ONCOPROTEIN WITH THE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR TRANSMEMBRANE DOMAIN AND THE EPIDERMAL GROWTH-FACTOR RECEPTOR CYTOPLASMIC DOMAIN SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN SARCOMA-VIRUS; AMINO-ACIDS; PROTEIN; GENE; EXPRESSION; TYPE-1; CDNA; POLYPEPTIDE; ACTIVATION; COMPONENT AB The bovine papillomavirus E5 transforming protein appears to activate both the epidermal growth factor receptor (EGF-R) and the platelet-derived growth factor receptor (PDGF-R) hy a ligand-independent mechanism. To further investigate the ability of E5 to activate receptors of different classes and to determine whether this stimulation occurs through the extracellular domain required for ligand activation, we constructed chimeric genes encoding PDGF-R and EGF-R by interchanging the extracellular, membrane, and cytoplasmic coding domains. Chimeras were transfected into NIH 3T3 and CHO(LR73) cells. All chimeras expressed stable protein which, upon addition of the appropriate ligand, could be activated as assayed by tyrosine autophosphorylation and biological transformation. Cotransfection of E5 with the wild-type and chimeric receptors resulted in the ligand-independent activation of receptors, provided that a receptor contained either the transmembrane domain of the PDGF-R or the cytoplasmic domain of the EGF-R. Chimeric receptors that contained both of these domains exhibited the highest level of E5-induced biochemical and biological stimulation. These results imply that E5 activates the PDGF-R and EGR-R by two distinct mechanisms, neither of which specifically involves the extracellular domain of the receptor. Consistent with the biochemical and biological activation data, coimmunoprecipitation studies demonstrated that E5 formed a complex with any chimera that contained a PDGF-R transmembrane domain or an EGF-R cytoplasmic domain, with those chimeras containing both domains demonstrating the greatest efficiency of complex formation. These results suggest that although different domains of the PDGF-R and EGF-R are required for E5 activation, both receptors are activated directly by formation of an E5-containing complex. C1 NCI,CELLULAR ONCOL LAB,BLDG 27,ROOM 1B23,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. FU NCI NIH HHS [IRTA TA-CA-B046] NR 31 TC 82 Z9 83 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 SEP PY 1993 VL 67 IS 9 BP 5303 EP 5311 PG 9 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700025 PM 8394451 ER PT J AU REINA, S MARKHAM, P GARD, E RAYED, F REITZ, M GALLO, RC VARNIER, OE AF REINA, S MARKHAM, P GARD, E RAYED, F REITZ, M GALLO, RC VARNIER, OE TI SEROLOGICAL, BIOLOGICAL, AND MOLECULAR CHARACTERIZATION OF NEW-ZEALAND WHITE-RABBITS INFECTED BY INTRAPERITONEAL INOCULATION WITH CELL-FREE HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID SCID-HU MOUSE; REVERSE-TRANSCRIPTASE; PERSISTENT INFECTION; HIV-1 INFECTION; CHIMPANZEES; AIDS; MODEL; DNA; TRANSMISSION; RETROVIRUSES AB The availability of a small laboratory animal model suitable for the evaluation of methods for prevention and treatment of human immunodeficiency virus type 1 infection would be a valuable resource for AIDS research. Here we describe the infection of a strain of domestic rabbits by intraperitoneal inoculation with cell-free human immunodeficiency virus type 1. Evidence of infection includes the presence of an immune response that has persisted for almost 3 years and the detection of and reisolation of infectious virus from peripheral blood mononuclear cells (PBMCs) and other tissues during the first 2 years. Typical viral proteins, DNA and RNA patterns, were observed in rabbit PBMCs and in cells infected by cocultivation with rabbit PBMCs. While a number of possible pathological changes were evaluated in infected rabbits, the presence of changes in lymph node structure similar to those reported in infected humans merits further investigation. C1 UNIV GENOA,SCH MED,INST MICROBIOL,HUMAN RETROVIROL LAB,I-16132 GENOA,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS,KENSINGTON,MD 20895. NR 41 TC 16 Z9 17 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 SEP PY 1993 VL 67 IS 9 BP 5367 EP 5374 PG 8 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700033 PM 7688823 ER PT J AU FU, W REIN, A AF FU, W REIN, A TI MATURATION OF DIMERIC VIRAL-RNA OF MOLONEY MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID CYS-HIS BOX; NUCLEOCAPSID PROTEIN; RETROVIRUS; MUTANTS AB We have analyzed the dimeric RNA present in Moloney murine leukemia virus (MoMuLV) particles. We found that the RNA in newly released virions is in a conformation different from that in mature virions, since it has a different electrophoretic mobility in nondenaturing agarose gels and dissociates into monomers at a lower temperature. On the basis of these results, we suggest that the RNA initially packaged into nascent virions is already dimeric but that the dimer undergoes a maturation process after the virus is released from the cell. In further experiments, we tested the possibility that this maturation event is linked to the maturation cleavage of the virion proteins, which is catalyzed by the viral protease (PR). We found that the dimeric RNA isolated from PR- mutant virions resembles that from immature virions: it has a lower electrophoretic mobility and a lower sedimentation rate, and it also dissociates at a lower temperature than does RNA from mature wild-type virions. When Kirsten sarcoma virus is rescued by a PR- mutant or by a somewhat leaky cysteine array mutant of MoMuLV, its RNA also exhibits a electrophoretic mobility lower than that in the wild-type pseudotype. These results suggest that the maturation of dimeric RNA in released virus particles requires the cleavage of the Gag precursor and the presence of an intact cysteine array in the released nucleocapsid protein. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74104] NR 26 TC 193 Z9 196 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 SEP PY 1993 VL 67 IS 9 BP 5443 EP 5449 PG 7 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700042 PM 8350405 ER PT J AU EGLITIS, MA EIDEN, MV WILSON, CA AF EGLITIS, MA EIDEN, MV WILSON, CA TI GIBBON APE LEUKEMIA-VIRUS AND THE AMPHOTROPIC MURINE LEUKEMIA-VIRUS 4070A EXHIBIT AN UNUSUAL INTERFERENCE PATTERN ON E36 CHINESE-HAMSTER CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID MAMMALIAN-CELLS; INFECTION; RETROVIRUS; LINES; GENE; LOCALIZATION; REGION AB The gibbon ape leukemia virus (GaLV), the amphotropic mouse leukemia virus (A-MLV) 4070A, and the xenotropic mouse leukemia virus (X-MLV) exhibit wide but not identical species host ranges. However, most Chinese hamster cells resist infection by all three viruses. We have now determined that the Chinese hamster cell line E36 differs from other Chinese hamster cell lines in that it is susceptible to infection by wild-type GaLV, A-MLV, and X-MLV. Surprisingly, analysis of the interference pattern of GaLV and A-MLV in E36 cells indicated that GaLV and A-MLV interfere in a nonreciprocal fashion. E36 cells productively infected with GaLV were resistant to superinfection by both GaLV and amphotropically packaged recombinant retroviral vectors. In contrast, E36 cells infected with A-MLV were resistant to superinfection with an amphotropic vector but could still be infected by a GaLV vector. These results imply the existence of a receptor on E36 cells that interacts with both GaLV and A-MLV. RP EGLITIS, MA (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 21 Z9 21 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 SEP PY 1993 VL 67 IS 9 BP 5472 EP 5477 PG 6 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700045 PM 8394458 ER PT J AU BARKSDALE, SK BAKER, CC AF BARKSDALE, SK BAKER, CC TI DIFFERENTIATION-SPECIFIC EXPRESSION FROM THE BOVINE PAPILLOMAVIRUS TYPE-1 P2443 AND LATE PROMOTERS SO JOURNAL OF VIROLOGY LA English DT Article ID OPEN READING FRAMES; TRANSFORMED-CELLS; INSITU HYBRIDIZATION; TRANSCRIPTIONAL REPRESSOR; MONOCLONAL-ANTIBODIES; E2 TRANSACTIVATOR; GENE-EXPRESSION; MESSENGER-RNAS; VIRAL-DNA; REGION AB The papillomavirus life cycle is tightly linked with keratinocyte differentiation in squamous epithelia. Vegetative viral DNA replication begins in the spinous layer, while synthesis of capsid proteins and virus maturation is restricted to the most differentiated or granular layer of the epithelium. In this study, in situ hybridization of bovine fibropapillomas was used to demonstrate that the activity of two promoters of bovine papillomavirus type 1 (BPV-t) is regulated in a differentiation-specific manner. In situ hybridization with a late promoter (P(L))-specific oligonucleotide probe suggested that P(L) is dramatically upregulated in the granular layer of the fibropapilloma. Northern (RNA) blot analysis of RNA from BPV-1-infected fibropapillomas indicated that the three major BPV-1 late-region mRNAs were transcribed from P(L). These RNAs include the previously described Ll (major capsid) mRNA as well as two larger mRNAs. The two larger mRNAs were characterized and shown to contain the L2 (minor capsid protein) open reading frame as well as the L1 open reading frame. In contrast to P(L), the P2443 promoter was maximally active in basal keratinocytes and the fibroma. The major mRNA transcribed from P1443 is the putative E5 oncoprotein mRNA which is spliced between nucleotides 2505 and 3225. No signal was detected above the basal layer with use of a probe specific for this mRNA. The E5 oncoprotein has previously been localized by immunoperoxidase staining to the granular cell layer as well as the basal cell layer of the fibropapilloma (S. Burnett, N. Jareborg, and D. DiMaio, Proc. Natl. Acad. Sci. USA 89:5665-5669, 1992). These data suggest that E5 proteins in the basal cell and granular cell layers are not translated from the same mRNA. C1 NCI, DIV CANC ETIOL,TUMOR VIRUS BIOL LAB,BLDG 41, ROOM C111, BETHESDA, MD 20892 USA. NCI, DIV CANC BIOL DIAG & CTR, PATHOL LAB, BETHESDA, MD 20892 USA. NR 63 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 1993 VL 67 IS 9 BP 5605 EP 5616 PG 12 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700060 PM 8394463 ER PT J AU ROSINARBESFELD, R RIVLIN, M NOIMAN, S MASHIAH, P YANIV, A MIKI, T TRONICK, SR GAZIT, A AF ROSINARBESFELD, R RIVLIN, M NOIMAN, S MASHIAH, P YANIV, A MIKI, T TRONICK, SR GAZIT, A TI STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF REV-LIKE TRANSCRIPTS OF EQUINE INFECTIOUS-ANEMIA VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID SIMIAN IMMUNODEFICIENCY VIRUS; NUCLEOTIDE-SEQUENCE ANALYSIS; HIV-1 REV; VISNA VIRUS; MESSENGER-RNA; TRANS-ACTIVATOR; GENE-EXPRESSION; SUBCELLULAR-LOCALIZATION; GENOME ORGANIZATION; MUTATIONAL ANALYSIS AB Three cDNA clones representing structurally distinct transcripts were isolated from a cDNA library prepared from cells infected with equine infectious anemia virus (EIAV) by using a probe representing the S3 open reading frame, which is thought to encode Rev. One species, designated p2/2, contained four exons and was identical to a previously described polycistronic mRNA that encodes Tat. This transcript was predicted to also direct the synthesis of a truncated form of the transmembrane protein and a putative Rev protein whose N-terminal 29 amino acids, derived from env, are linked to S3 sequences. The second cDNA, p176, also consisted of four exons which were generated by two of three of the same splicing events that occur with p2/2 but not with the Tat mRNA. The alternative splice site giving rise to the second exon of p176 results in a bicistronic message that would encode the same transmembrane and Rev proteins as p2/2. The first exon of the third transcript, p20, was identical to those of p2/2 and p176 but was spliced directly to S3. This monocistronic message could encode a second form of Rev that lacks env sequences, provided that Rev synthesis would initiate at a non-AUG codon. The coding capacity of each cDNA was assessed in a eukaryotic system using S3 antisera. Two putative Rev proteins with apparent molecular masses of 18 and 16 kDa were expressed by p2/2 and p176, while p20 expressed only a 16-kDa species. Analysis of EIAV-infected cells with S3 antisera revealed the presence of an 18-kDa protein. Surprisingly, the same protein was detected in purified virions. By using a reporter construct, the chloramphenicol acetyltransferase gene linked to EIAV env sequences, we were able to demonstrate greatly enhanced chloramphenicol acetyltransferase activity in cells cotransfected with this construct and any of the three cDNAs. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NR 52 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1993 VL 67 IS 9 BP 5640 EP 5646 PG 7 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700064 PM 8394464 ER PT J AU KROHN, KJE HAKKARAINEN, K AAVIK, E DEWHURST, S SADAIE, R MULLINS, JI AF KROHN, KJE HAKKARAINEN, K AAVIK, E DEWHURST, S SADAIE, R MULLINS, JI TI TRANSCOMPLEMENTATION OF SIMIAN IMMUNODEFICIENCY VIRUS REV WITH HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I REX SO JOURNAL OF VIROLOGY LA English DT Note ID MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; STRUCTURED REGION; REGULATORY GENES; SIV VACCINE; HTLV-III; PROTEIN; HIV-1; MACAQUES; BINDING AB A molecular clone of the simian immunodeficiency virus SIV(SMM) isolate PBj14, lacking the ATG initiation codon for Rev protein (PBj-1.5), did not produce virus or large unspliced or singly spliced viral RNA upon transfection of HeLa cells. Low but significant levels of virus and large viral RNA production were observed upon transfection of PBj-1.5 into HeLa Rev cells expressing the rev gene of human immunodeficiency virus type 1. Furthermore, abundant virus and large viral RNA production occurred upon transfection of PBj-1.5 into HeLa Rex cells expressing the rex gene of human T-cell leukemia virus type 1. Virus produced from HeLa Rex and HELa Rev transfections was infectious, produced large amounts of virus, and was cytopathic for Rex-producing MT4 cells. In contrast, no or only low levels of virus production were observed upon infection of H9 cells. These studies show that a defective SIV rev gene can be transcomplemented with human immunodeficiency vims type 1 Rev and with high efficiency by human T-cell leukemia virus type I Rex, and they suggest that rev-defective viruses could serve as a source for production of a live attenuated SIV vaccine. C1 STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP KROHN, KJE (reprint author), UNIV TAMPERE,INST BIOMED SCI,SF-33101 TAMPERE,FINLAND. FU PHS HHS [A127136] NR 33 TC 2 Z9 2 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 SEP PY 1993 VL 67 IS 9 BP 5681 EP 5684 PG 4 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700072 PM 8350422 ER PT J AU WOLFFE, EJ ISAACS, SN MOSS, B AF WOLFFE, EJ ISAACS, SN MOSS, B TI DELETION OF THE VACCINIA VIRUS B5R GENE ENCODING A 42-KILODALTON MEMBRANE GLYCOPROTEIN INHIBITS EXTRACELLULAR VIRUS ENVELOPE FORMATION AND DISSEMINATION (VOL 67, PG 4738, 1993) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition RP WOLFFE, EJ (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 8 Z9 8 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 SEP PY 1993 VL 67 IS 9 BP 5709 EP 5711 PG 3 WC Virology SC Virology GA LR777 UT WOS:A1993LR77700078 ER PT J AU BROWN, EW MITHTHAPALA, S OBRIEN, SJ AF BROWN, EW MITHTHAPALA, S OBRIEN, SJ TI PREVALENCE OF EXPOSURE TO FELINE IMMUNODEFICIENCY VIRUS IN EXOTIC FELID SPECIES SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE FELINE IMMUNODEFICIENCY VIRUS; SEROPREVALENCE; EPIDEMIOLOGY; FELIDAE ID GENETIC DIVERSITY; CATS; INFECTION; CHEETAHS; RETROVIRUSES; LENTIVIRUS; LIONS AB Feline immunodeficiency virus (FIV) is a novel lentivirus that causes T-cell deficiency in the domestic cat (Felis catus). Recent studies have revealed the existence of antigenically similar lentiviruses in a large number of nondomestic felid species. We summarize here a comprehensive serological survey for FIV cross-reactive antibodies in free-ranging and captive felid populations. Serum or plasma samples from 1, 645 animals representing 20 felid species were screened by western blot analysis for exposure to one or more lentiviral proteins. Feline lentiviruses were confirmed to be endemic in several East and South African populations of lion (Panthera leo). Exposure was also detected in nearly all of the natural North American puma (Felis concolor) populations surveyed. Antibodies to FIV were also found in a free-ranging population of cheetah (Acinonyx jubatus). Lentivirus presence among captive exotic cats in the United States and abroad appears to be sporadic and infrequent. Because FIV is endemic in certain natural populations and absent in others, these data suggest that lentivirus infection postdated the geographic separation of felid populations; and therefore, spread of the virus into other seronegative populations may now be restricted by natural geographical barriers. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP BROWN, EW (reprint author), PROGRAM RESOURCES INC,DYNECORP,NCI,FCRDC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 26 TC 43 Z9 43 U1 0 U2 3 PU AMER ASSOC Z00 VETERINARIANS PI MEDIA PA 6 NORTH PENNELL ROAD, MEDIA, PA 19063 SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD SEP PY 1993 VL 24 IS 3 BP 357 EP 364 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA ME071 UT WOS:A1993ME07100017 ER PT J AU GURALNIK, JM SIMONSICK, EM AF GURALNIK, JM SIMONSICK, EM TI PHYSICAL-DISABILITY IN OLDER AMERICANS SO JOURNALS OF GERONTOLOGY LA English DT Article RP GURALNIK, JM (reprint author), NATL INST AGING,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,SUITE 3C-309,7201 WISCONSIN AVE,BETHESDA,MD, USA. NR 27 TC 160 Z9 160 U1 5 U2 8 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 SI SI BP 3 EP 10 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA MA482 UT WOS:A1993MA48200002 PM 8409237 ER PT J AU JOSEPH, JA ROTH, GS AF JOSEPH, JA ROTH, GS TI HORMONAL-REGULATION OF MOTOR BEHAVIOR IN SENESCENCE SO JOURNALS OF GERONTOLOGY LA English DT Article ID STRIATAL DOPAMINE-RECEPTORS; MUSCARINIC RECEPTORS; ESTROGEN-TREATMENT; MESSENGER-RNA; RAT-BRAIN; CHRONIC PROLACTIN; ACETYLCHOLINE-RELEASE; ANTERIOR-PITUITARY; SUPER-SENSITIVITY; RABBIT STRIATUM C1 FRANCIS SCOTT KEY MED CTR,NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 75 TC 20 Z9 20 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 SI SI BP 51 EP 55 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA MA482 UT WOS:A1993MA48200008 PM 8409241 ER PT J AU KAWATE, R TALAN, MI ENGEL, BT AF KAWATE, R TALAN, MI ENGEL, BT TI AGED C57BL 6J MICE RESPOND TO COLD WITH INCREASED SYMPATHETIC NERVOUS ACTIVITY TO INTERSCAPULAR BROWN ADIPOSE-TISSUE SO JOURNALS OF GERONTOLOGY LA English DT Article ID METABOLIC HEAT-PRODUCTION; ELDERLY RATS; STRESS; TOLERANCE; ADULT; MAC AB Aged, male C57BL/6J mice produce less heat than adults during cold, which may lead to a reduced ability to maintain core temperature, but the underlying mechanisms of the decreased heat production in aged mice are still unclear. We measured sympathetic nervous activity (SNA) to interscapular brown adipose tissue (IBAT) in aged mice and compared this activity with that of adults. Mice were anesthetized by urethane and isoflurane, and SNA was recorded from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing iced-water to decrease colonic temperature 7-degrees-C below control over 20 minutes. SNA to IBAT (IBAT-SNA) increased during cold in both groups, but aged mice had higher IBAT-SNA before and during cold. These findings indicate that neither the ability of aged mice to detect cold nor their ability to generate sympathetic outflow to BAT is deficient. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 16 TC 16 Z9 16 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 IS 5 BP B180 EP B183 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LY226 UT WOS:A1993LY22600021 PM 8366256 ER PT J AU WU, AJ ATKINSON, JC FOX, PC BAUM, BJ SHIP, JA AF WU, AJ ATKINSON, JC FOX, PC BAUM, BJ SHIP, JA TI CROSS-SECTIONAL AND LONGITUDINAL ANALYSES OF STIMULATED PAROTID SALIVARY CONSTITUENTS IN HEALTHY, DIFFERENT-AGED SUBJECTS SO JOURNALS OF GERONTOLOGY LA English DT Article ID FLOW-RATE; SECRETION; GLANDS; PROTEINS; LACTOFERRIN; PEOPLE; OLD AB Background. Salivary gland dysfunction has traditionally been associated with old age, and complaints of xerostomia are common in an elderly population. Measurement of certain salivary constituents can provide information about the functional ability of discrete areas of the salivary gland. To our knowledge, this is the first longitudinal study to examine levels of salivary constituents in stimulated parotid saliva in a population of different-aged persons. Methods. The levels of five salivary constituents (total protein, lactoferrin, proline-rich proteins, sodium, and potassium) were measured in stimulated parotid saliva of 47 healthy, unmedicated men and women over a 10.5 year period. Results. There were no significant age-related decreases in the presence of total protein, lactoferrin, proline-rich proteins, sodium, and potassium in this exocrine secretion. Conclusions. These data confirm and extend previous cross-sectional studies of salivary constituents, indicating that parotid gland function is maintained in healthy aging individuals. RP WU, AJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 32 TC 34 Z9 34 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 IS 5 BP M219 EP M224 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LY226 UT WOS:A1993LY22600006 PM 8366264 ER PT J AU HADLEY, EC ORY, MG SUZMAN, R WEINDRUCH, R AF HADLEY, EC ORY, MG SUZMAN, R WEINDRUCH, R TI PHYSICAL FRAILTY - A TREATABLE CAUSE OF DEPENDENCE IN OLD-AGE - FOREWORD SO JOURNALS OF GERONTOLOGY LA English DT Editorial Material C1 NATL INST AGING,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD. UNIV WISCONSIN,INST AGING,MADISON,WI 53706. RP HADLEY, EC (reprint author), NATL INST AGING,GERIATR PROGRAM,BETHESDA,MD, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 SI SI BP R7 EP R8 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA MA482 UT WOS:A1993MA48200001 ER PT J AU MAROTTOLI, RA OSTFELD, AM MERRILL, SS PERLMAN, GD FOLEY, DJ COONEY, LM AF MAROTTOLI, RA OSTFELD, AM MERRILL, SS PERLMAN, GD FOLEY, DJ COONEY, LM TI DRIVING CESSATION AND CHANGES IN MILEAGE DRIVEN AMONG ELDERLY INDIVIDUALS SO JOURNALS OF GERONTOLOGY LA English DT Article ID OLDER DRIVER; DEMENTIA; HEALTH AB The factors associated with driving cessation, number of miles driven, and changes in mileage were assessed in a community-living elderly population. A driving survey was administered in 1989 to surviving members of the New Haven EPESE cohort. Of 1,331 respondents, 456 had driven and 139 had stopped driving between 1983 and 1989. Independent predictors of driving cessation from a multiple logistic regression model included higher age, lower income, not working, neurologic disease, cataracts, lower physical activity level, and functional disability. These risk factors were combined to assess their ability to predict driving cessation. If no factors were present, no subjects stopped driving; if one or two factors were present, 17 percent stopped, if three or more factors were present, 49 percent stopped. A long with the expected medical factors, physical activity level and social and economic factors contributed to driving cessation. High mileage drivers tended to be younger, active males who still worked. Increasing age and disability were associated with mileage reduction compared to five years earlier. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06504. VET ADM MED CTR,W HAVEN,CT. NIA,BETHESDA,MD 20892. RP MAROTTOLI, RA (reprint author), YALE UNIV,SCH MED,DEPT MED,GERIATR SECT,TOMPKINS 6,20 YORK ST,NEW HAVEN,CT 06504, USA. NR 15 TC 95 Z9 95 U1 2 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1993 VL 48 IS 5 BP S255 EP S260 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LY226 UT WOS:A1993LY22600016 PM 8366274 ER PT J AU LINET, MS HUMPHREY, RL MEHL, ES BROWN, LM POTTERN, LM BIAS, WB MCCAFFREY, L AF LINET, MS HUMPHREY, RL MEHL, ES BROWN, LM POTTERN, LM BIAS, WB MCCAFFREY, L TI A CASE-CONTROL AND FAMILY STUDY OF WALDENSTROMS MACROGLOBULINEMIA SO LEUKEMIA LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; SMOKING; SYSTEM AB Waldenstrom's macroglobulinemia (WM) is a rare disorder of lymphoid and plasma cells characterized by an immunoglobulin M (IgM) monoclonal gammopathy, clinical and immunopathologic similarities with other lymphoproliferative neoplasms, but the etiology of which is unknown. We undertook the first case-control study of this disorder among 65 cases, comprising 87% of all WM patients diagnosed during 1969-1983 in the greater Baltimore, Maryland area. Compared with 213 hospital controls without cancer, cases were slightly better educated, but there were otherwise no differences in sociodemographic factors, history of prior medical conditions, medication use, cigarette smoking, alcohol consumption, specific occupational exposures, employment in any particular industries or occupations, or familial cancer history. Cases were more likely than controls to have first-degree relatives with a history of pneumonia, diphtheria, rheumatic fever, and diabetes mellitus. An exploratory evaluation of immunologic profiles of first-degree relatives of 48% of families ot cases revealed that relatives of two cases had asymptomatic IgM (>750 mg/dl) monoclonal gammopathy and close to 40% of the 109 evaluated had diverse immunologic abnormalities. Larger population-based case-control studies are needed to further evaluate the suggestive evidence of immune dysfunction among families of WM cases. C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. WESTAT CORP,BALTIMORE,MD. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. RP LINET, MS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415B,ROCKVILLE,MD 20892, USA. FU NCI NIH HHS [R01CA33822] NR 30 TC 32 Z9 34 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 1993 VL 7 IS 9 BP 1363 EP 1369 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA MA144 UT WOS:A1993MA14400009 PM 8371587 ER PT J AU ZHOU, GX SCHMITT, JM WALKER, EC AF ZHOU, GX SCHMITT, JM WALKER, EC TI ELECTROOPTICAL SIMULATOR FOR PULSE OXIMETERS SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Note DE LIGHT; LIQUID CRYSTAL; OXIMETRY; OXYGEN SATURATION; POLARIZATION; PULSE OXIMETRY; SIMULATOR RP ZHOU, GX (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 2 PU PETER PEREGRINUS LTD PI HERTS PA SOUTHGATE HOUSE STEVENAGE PO BOX 8, HERTS, ENGLAND SG1 1HQ SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 1993 VL 31 IS 5 BP 534 EP 539 DI 10.1007/BF02441991 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA MG130 UT WOS:A1993MG13000014 PM 8295445 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI OPPORTUNISTIC NOSOCOMIAL INFECTIONS - TREATMENT AND DEVELOPMENTAL THERAPEUTICS .2. CRYPTOCOCCOSIS SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AMPHOTERICIN-B; COMBINATION THERAPY; CUTANEOUS CRYPTOCOCCOSIS; ANTIFUNGAL ANTIBIOTICS; MURINE CRYPTOCOCCOSIS; ORAL FLUCONAZOLE; PRADIMICIN-A; EXPERIMENTAL CANDIDIASIS; ITRACONAZOLE THERAPY RP STGEORGIEV, V (reprint author), NIAID,SOLAR BLDG,ROOM 4C-39,BETHESDA,MD 20892, USA. NR 159 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1993 VL 13 IS 5 BP 507 EP 527 PG 21 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT704 UT WOS:A1993LT70400001 PM 8412406 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI OPPORTUNISTIC NOSOCOMIAL INFECTIONS - TREATMENT AND DEVELOPMENTAL THERAPEUTICS - TOXOPLASMOSIS SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CENTRAL-NERVOUS-SYSTEM; IMMUNE-DEFICIENCY-SYNDROME; LIPID-SOLUBLE ANTIFOLATE; ANTI-MICROBIAL ACTIVITY; PYRIMETHAMINE-SULFADIAZINE COMBINATION; GONDII BEVERLEY STRAIN; CONGENITAL TOXOPLASMOSIS; CEREBRAL TOXOPLASMOSIS; OCULAR TOXOPLASMOSIS RP STGEORGIEV, V (reprint author), NIAID,SOLAR BLDG,ROOM 4C-39,BETHESDA,MD 20892, USA. NR 327 TC 6 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1993 VL 13 IS 5 BP 529 EP 568 PG 40 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT704 UT WOS:A1993LT70400002 PM 8412407 ER PT J AU KNOX, SS MCCANN, BS AF KNOX, SS MCCANN, BS TI BIOBEHAVIORAL MECHANISMS IN LIPID-METABOLISM AND ATHEROSCLEROSIS - AN OVERVIEW SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID HOSTILITY RP KNOX, SS (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1993 VL 42 IS 9 SU 1 BP 1 EP 2 DI 10.1016/0026-0495(93)90254-L PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA481 UT WOS:A1993MA48100001 PM 8412781 ER PT J AU SHIVELY, CA KNOX, SS SHERWIN, BB WALSH, BW WILSON, PWF AF SHIVELY, CA KNOX, SS SHERWIN, BB WALSH, BW WILSON, PWF TI SEX STEROIDS, PSYCHOSOCIAL FACTORS, AND LIPID-METABOLISM SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT WORKSHOP ON BIOBEHAVIORAL MECHANISMS IN LIPID METABOLISM AND ATHEROSCLEROSIS CY JAN 24-26, 1993 CL BETHESDA, MD SP NHLBI ID CORONARY HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; ARTERY ATHEROSCLEROSIS; CYNOMOLGUS MONKEYS; MENSTRUAL-CYCLE; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MENOPAUSAL WOMEN; SOCIAL-STATUS; RISK-FACTORS C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,BEHAV MED BRANCH,BETHESDA,MD 20892. MCGILL UNIV,DEPT PSYCHOL,MONTREAL H3A 2T5,QUEBEC,CANADA. MCGILL UNIV,DEPT OBSTET & GYNECOL,MONTREAL H3A 2T5,QUEBEC,CANADA. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RP SHIVELY, CA (reprint author), BOWMAN GRAY SCH MED,DEPT COMPARAT MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 81 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1993 VL 42 IS 9 SU 1 BP 16 EP 24 DI 10.1016/0026-0495(93)90256-N PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA481 UT WOS:A1993MA48100003 PM 8412782 ER PT J AU MULDOON, MF ROSSOUW, JE MANUCK, SB GLUECK, CJ KAPLAN, JR KAUFMANN, PG AF MULDOON, MF ROSSOUW, JE MANUCK, SB GLUECK, CJ KAPLAN, JR KAUFMANN, PG TI LOW OR LOWERED CHOLESTEROL AND RISK OF DEATH FROM SUICIDE AND TRAUMA SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT WORKSHOP ON BIOBEHAVIORAL MECHANISMS IN LIPID METABOLISM AND ATHEROSCLEROSIS CY JAN 24-26, 1993 CL BETHESDA, MD SP NHLBI ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; FACTOR INTERVENTION TRIAL; TOTAL SERUM-CHOLESTEROL; FATTY-ACID COMPOSITION; COENZYME-A REDUCTASE; FOLLOW-UP; PLASMA-CHOLESTEROL; BLOOD-LIPIDS; MYOCARDIAL-INFARCTION C1 NHLBI,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT PSYCHOL,PITTSBURGH,PA 15260. JEWISH HOSP CINCINNATI,CTR CHOLESTEROL,CINCINNATI,OH 45229. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27103. RP MULDOON, MF (reprint author), UNIV PITTSBURGH,MED CTR,CTR CLIN PHARMACOL,4015 OHARA ST,506 OLD ENGN HALL,PITTSBURGH,PA 15260, USA. FU NHLBI NIH HHS [HL 26551, HL 40962, HL 46328] NR 125 TC 66 Z9 67 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1993 VL 42 IS 9 SU 1 BP 45 EP 56 DI 10.1016/0026-0495(93)90259-Q PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA481 UT WOS:A1993MA48100006 PM 8412786 ER PT J AU KOCKEN, CHM JANSEN, J KAAN, AM BECKERS, PJA PONNUDURAI, T KASLOW, DC KONINGS, RNH SCHOENMAKERS, JGG AF KOCKEN, CHM JANSEN, J KAAN, AM BECKERS, PJA PONNUDURAI, T KASLOW, DC KONINGS, RNH SCHOENMAKERS, JGG TI CLONING AND EXPRESSION OF THE GENE CODING FOR THE TRANSMISSION-BLOCKING TARGET ANTIGEN PFS48/45 OF PLASMODIUM-FALCIPARUM SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE MALARIA; PLASMODIUM-FALCIPARUM; GAMETOCYTE; SURFACE ANTIGEN; TRANSMISSION-BLOCKING IMMUNITY ID SEXUAL STAGE ANTIGENS; IMMUNE-RESPONSES; MESSENGER-RNAS; ANTIBODIES; PROTEINS; SYSTEM AB The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of Plasmodium falciparum has been cloned. The Pfs48/45 gene is a non-interrupted, single copy gene that codes for a hydrophobic, non-repetitive protein of 448 amino acid residues containing a putative signal peptide at the N-terminus, a hydrophobic C-terminus and 7 potential N-glycosylation sites. Antibodies directed against a Pfs48/45-glutathione-S-transferase fusion protein reacted with both the 45-kDa and 48-kDa proteins of gametocytes. When Pfs48/45 is expressed in the baculovirus-insect cell system the recombinant Pfs48/45 protein is targeted and exposed to the insect cell surface in such a configuration that it is recognized by transmission-blocking anti-45/48-kDa monoclonal antibodies. C1 CATHOLIC UNIV NIJMEGEN,FAC SCI,DEPT MOLEC BIOL,6525 ED NIJMEGEN,NETHERLANDS. CATHOLIC UNIV NIJMEGEN,FAC MED,INST MED PARASITOL,6525 ED NIJMEGEN,NETHERLANDS. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 32 TC 83 Z9 84 U1 0 U2 0 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 SEP PY 1993 VL 61 IS 1 BP 59 EP 68 DI 10.1016/0166-6851(93)90158-T PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA LZ796 UT WOS:A1993LZ79600006 PM 8259133 ER PT J AU DOLAN, SA HERRFELDT, JA WELLEMS, TE AF DOLAN, SA HERRFELDT, JA WELLEMS, TE TI RESTRICTION POLYMORPHISMS AND FINGERPRINT PATTERNS FROM AN INTERSPERSED REPETITIVE ELEMENT OF PLASMODIUM-FALCIPARUM DNA SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM-FALCIPARUM; MALARIA; DNA FINGERPRINTING; GENETIC MARKER; CLONE ID CHROMOSOME SIZE POLYMORPHISMS; RICH PROTEIN GENE; P-FALCIPARUM; MALARIA PARASITES; RESISTANCE; CROSS; PYRIMETHAMINE; INVITRO; RECOMBINATION; HETEROGENEITY AB A recombinant DNA clone, pC4.H32, identifies distinguishable restriction fragment patterns from different Plasmodium falciparum clones. Analysis of these DNA fingerprint patterns from parasites cultivated over several years and from progeny of a P. falciparum cross showed the fingerprints to be mitotically and meiotically stable. Restriction fragments from the parents of the cross possessed sufficient polymorphism and number to generate 14 unique fingerprint patterns in 16 independent recombinant progeny. The pC4.H32 insert contains a 0.5-kb imperfectly repeated sequence found in subtelomeric regions of multiple chromosomes. Restriction site variations both within and outside of the 0.5-kb repeat contribute to the fingerprint polymorphisms. Fingerprint analysis can serve to type P. falciparum clones and can detect mislabeling and cross-contamination of parasite stocks. C1 NIAID, MALARIA RES LAB, BLDG 4, ROOM 126, NIH CAMPUS, BETHESDA, MD 20892 USA. NR 36 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 EI 1872-9428 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD SEP PY 1993 VL 61 IS 1 BP 137 EP 142 DI 10.1016/0166-6851(93)90166-U PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA LZ796 UT WOS:A1993LZ79600014 PM 7903115 ER PT J AU UNGER, T MIETZ, JA SCHEFFNER, M YEE, CL HOWLEY, PM AF UNGER, T MIETZ, JA SCHEFFNER, M YEE, CL HOWLEY, PM TI FUNCTIONAL DOMAINS OF WILD-TYPE AND MUTANT P53 PROTEINS INVOLVED IN TRANSCRIPTIONAL REGULATION, TRANSDOMINANT INHIBITION, AND TRANSFORMATION SUPPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING; GENE-EXPRESSION; SV40-TRANSFORMED CELLS; TUMOR-ANTIGEN; T-ANTIGEN; ADENOVIRUS; MUTATIONS; ONCOGENE; SEQUENCE; ELEMENT AB The wild-type (wt) p53 protein has transcriptional activation functions which may be linked to its tumor suppressor activity. Many mutant p53 proteins expressed in cancers have lost the ability to function as transcriptional activators and furthermore may inhibit wt p53 function. To study the mechanisms by which mutant forms of p53 have lost their transactivation function and can act in a dominant negative manner, a structure-function analysis of both mutant and engineered truncated forms of p53 was carried out. We show that different mutant p53 proteins found in cancers vary in the ability to inhibit the transcriptional transactivation and specific DNA binding activities of wt human p53. This transdominant effect was mediated through the carboxy-terminal oligomerization region. The role of the transactivation activity in transformation suppression by wt p53 was also examined by constructing an N-terminal deletion mutant lacking the transactivation domain. This mutant was unable to transactivate but could bind specifically to DNA. Although it was impaired in its ability to suppress transformation of primary rat embryo fibroblasts by adenovirus E1A plus activated ras, the N-terminal deletion mutant still had some suppression activity, suggesting that additional functions of p53 may contribute to transformation suppression. RP UNGER, T (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Scheffner, Martin/K-2940-2012 OI Scheffner, Martin/0000-0003-2229-0128 NR 62 TC 132 Z9 132 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1993 VL 13 IS 9 BP 5186 EP 5194 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300007 PM 8355677 ER PT J AU GORDENIN, DA LOBACHEV, KS DEGTYAREVA, NP MALKOVA, AL PERKINS, E RESNICK, MA AF GORDENIN, DA LOBACHEV, KS DEGTYAREVA, NP MALKOVA, AL PERKINS, E RESNICK, MA TI INVERTED DNA REPEATS - A SOURCE OF EUKARYOTIC GENOMIC INSTABILITY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BACTERIAL TRANSPOSON TN5; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; YEAST SACCHAROMYCES; PRECISE EXCISION; MUTANTS; RECOMBINATION; MUTATIONS; CONVERSION; POLYMERASE AB While inverted DNA repeats are generally acknowledged to be an important source of genetic instability in prokaryotes, relatively little is known about their effects in eukaryotes. Using bacterial transposon Tn5 and its derivatives, we demonstrate that long inverted repeats also cause genetic instability leading to deletion in the yeast Saccharomyces cerevisiae. Furthermore, they induce homologous recombination. Replication plays a major role in the deletion formation. Deletions are stimulated by a mutation in the DNA polymerase delta gene (pol3). The majority of deletions result from imprecise excision between small (14- to 6-bp) repeats in a polar fashion, and they often generate quasipalindrome structures that subsequently may be highly unstable. Breakpoints are clustered near the ends of the long inverted repeats (< 150 bp). The repeats have both intra- and interchromosomal effects in that they also create hot spots for mitotic interchromosomal recombination. Intragenic recombination is 4 to 18 times more frequent for heteroalleles in which one of the two mutations is due to the insertion of a long inverted repeat, compared with other pairs of heteroalleles in which neither mutation has a long repeat. We propose that both deletion and recombination are the result of altered replication at the basal part of the stem formed by the inverted repeats. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RP GORDENIN, DA (reprint author), ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 37 TC 140 Z9 143 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1993 VL 13 IS 9 BP 5315 EP 5322 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300019 PM 8395002 ER PT J AU NEY, PA ANDREWS, NC JANE, SM SAFER, B PURUCKER, ME WEREMOWICZ, S MORTON, CC GOFF, SC ORKIN, SH NIENHUIS, AW AF NEY, PA ANDREWS, NC JANE, SM SAFER, B PURUCKER, ME WEREMOWICZ, S MORTON, CC GOFF, SC ORKIN, SH NIENHUIS, AW TI PURIFICATION OF THE HUMAN NF-E2 COMPLEX - CDNA CLONING OF THE HEMATOPOIETIC CELL-SPECIFIC SUBUNIT AND EVIDENCE FOR AN ASSOCIATED PARTNER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; DOMINANT CONTROL REGION; PORPHOBILINOGEN DEAMINASE GENE; SULFATE-POLYACRYLAMIDE GELS; SODIUM DODECYL-SULFATE; TRANSGENIC MICE; TRANSCRIPTION FACTORS; CHROMATIN STRUCTURE; ERYTHROID PROMOTER; RNA-POLYMERASE AB The human globin locus control region-binding protein, NF-E2, was purified by DNA affinity chromatography. Its tissue-specific component, p45 NF-E2, was cloned by use of a low-stringency library screen with murine p45 NF-E2 cDNA (N. C. Andrews, H. Erdjument-Bromage, M. B. Davidson, P. Tempst, and S. H. Orkin, Nature (London] 362:722-728, 1993). The human p45 NF-E2 gene was localized to chromosome 12q13 by fluorescent in situ hybridization. Human p45 NF-E2 and murine p45 NF-E2 are highly homologous basic region-leucine zipper (bZIP) proteins with identical DNA-binding domains. Immunoprecipitation experiments demonstrated that p45 NF-E2 is associated in vivo with an 18-kDa protein (p18). Because bZIP proteins bind DNA as dimers, we infer that native NF-E2 must be a heterodimer of 45- and 18-kDa subunits. Although AP-1 and CREB copurified with NF-E2, no evidence was found for heterodimer formation between p45 NF-E2 and proteins other than p18. Thus, p18 appears to be the sole specific partner of p45 NF-E2 in erythroid cells. Cloning of human p45 NF-E2 should permit studies of the role of NF-E2 in globin gene regulation and erythroid differentiation. C1 NHLBI, MOLEC HEMATOL LAB, BETHESDA, MD 20892 USA. HARVARD UNIV, CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST, DEPT PEDIAT,DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RP NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. RI Jane, Stephen/D-6659-2011; OI Andrews, Nancy/0000-0003-0243-4462 NR 51 TC 166 Z9 168 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1993 VL 13 IS 9 BP 5604 EP 5612 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300046 PM 8355703 ER PT J AU FAZIOLI, F MINICHIELLO, L MATOSKOVA, B WONG, WT DIFIORE, PP AF FAZIOLI, F MINICHIELLO, L MATOSKOVA, B WONG, WT DIFIORE, PP TI EPS15, A NOVEL TYROSINE KINASE SUBSTRATE, EXHIBITS TRANSFORMING ACTIVITY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PHOSPHOLIPASE-C-GAMMA; GTPASE-ACTIVATING PROTEIN; FACTOR RECEPTOR KINASE; AMINO-ACID-SEQUENCE; PDGF BETA-RECEPTOR; SIGNAL TRANSDUCTION; EGF RECEPTOR; PHOSPHATIDYLINOSITOL-3 KINASE; MOLECULAR-CLONING AB An expression cloning method which allows direct isolation of cDNAs encoding substrates for tyrosine kinases was applied to the study of the epiderma growth factor (EGF) receptor (EGFR) signaling pathway. A previously undescribed cDNA was isolated and designated eps15. The structural features of the predicted eps15 gene product allow its subdivision into three domains. Domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains. Domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases. Antibodies specific for the eps15 gene product recognize two proteins: a major species of 142 kDa and a minor component of 155 kDa, both of which are phosphorylated on tyrosine following EGFR activation by EGF in vivo. EGFR is also able to directly phosphorylate the eps15 product in vitro. In addition, phosphorylation of the eps15 gene product in vivo is relatively receptor specific, since the erbB-2 kinase phosphorylates it very inefficiently. Finally, overexpression of eps15 is sufficient to transform NIH 3T3 cells, thus suggesting that the eps15 gene product is involved in the regulation of mitogenic signals. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NATL INST DENTAL RES, CELLULAR DEV & ONCOL LAB, BETHESDA, MD 20892 USA. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 67 TC 239 Z9 243 U1 1 U2 7 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 SEP PY 1993 VL 13 IS 9 BP 5814 EP 5828 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300066 PM 7689153 ER PT J AU MACDONALD, PN DOWD, DR NAKAJIMA, S GALLIGAN, MA REEDER, MC HAUSSLER, CA OZATO, K HAUSSLER, MR AF MACDONALD, PN DOWD, DR NAKAJIMA, S GALLIGAN, MA REEDER, MC HAUSSLER, CA OZATO, K HAUSSLER, MR TI RETINOID-X RECEPTORS STIMULATE AND 9-CIS RETINOIC ACID INHIBITS 1,25-DIHYDROXYVITAMIN D3-ACTIVATED EXPRESSION OF THE RAT OSTEOCALCIN GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID VITAMIN-D RECEPTOR; THYROID-HORMONE RECEPTORS; D-RESPONSIVE ELEMENT; NUCLEAR-PROTEIN; RXR-ALPHA; DNA; BINDING; IDENTIFICATION; TRANSCRIPTION; HOMODIMER AB The vitamin D receptor (VDR) binds the vitamin D-responsive element (VDRE) as a heterodimer with an unidentified receptor auxiliary factor (RAF) present in mammalian cell nuclear extracts. VDR also interacts with the retinoid X receptors (RXRs), implying that RAF may be related to the RXRs. Here we demonstrate that highly purified HeLa cell RAF contained RXRbeta immunoreactivity and that both activities copurified and precisely coeluted in high-resolution hydroxylapatite chromatography. Furthermore, an RXRbeta-specific antibody disrupted VDR-RAF-VDRE complexes in mobility shift assays. These data strongly indicate that HeLa RAF is highly related to or is identical to RXRbeta. Consequently, the effect of the 9-cis retinoic acid ligand for RXRs was examined in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-activated gene expression systems. Increasing concentrations of 9-cis retinoic acid (1 nM to 1 muM) markedly reduced 1,25(OH)2D3-dependent accumulation of osteocalcin mRNA in osteoblast-like ROS 17/2.8 cells. All-trans retinoic acid also interfered with vitamin D responsiveness, but it was consistently less potent than the 9-cis isomer. Transient transfection studies revealed that attenuation by 9-cis retinoic acid was at the transcriptional level and was mediated through interactions at the osteocalcin VDRE. Furthermore, overexpression of both RXRbeta and RXRalpha augmented 1,25(OH)2D3 responsiveness in transient expression studies. Direct analysis of VDRE binding in mobility shift assays demonstrated that heteromeric interactions between VDR and RXR were enhanced by 1,25(OH)2D3 and were not affected appreciably by 9-cis retinoic acid, except that inhibition was observed at high retinoid concentrations. These data suggest a regulatory mechanism for osteocalcin gene expression that involves 1,25(OH)2D3-induced heterodimerization of VDR and unliganded RXR. 9-cis retinoic acid may attenuate 1,25(OH)2D3 responsiveness by diverting RXRs away from VDR-mediated transcription and towards other RXR-dependent transcriptional pathways. C1 UNIV ARIZONA,COLL MED,DEPT BIOCHEM,TUCSON,AZ 85724. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. ST LOUIS UNIV,SCH MED,E A DOISY DEPT BIOCHEM & MOLEC BIOL,ST LOUIS,MO 63104. FU NIAMS NIH HHS [AR-15781]; NIDDK NIH HHS [DK-33351]; NIGMS NIH HHS [1-F32-GM-13846] NR 48 TC 223 Z9 224 U1 0 U2 4 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 SEP PY 1993 VL 13 IS 9 BP 5907 EP 5917 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300074 PM 8395017 ER PT J AU ZHAN, QM CARRIER, F FORNACE, AJ AF ZHAN, QM CARRIER, F FORNACE, AJ TI INDUCTION OF CELLULAR P53 ACTIVITY BY DNA-DAMAGING AGENTS AND GROWTH ARREST (VOL 13, PG 4249, 1993) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition RP ZHAN, QM (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008 NR 1 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1993 VL 13 IS 9 BP 5928 EP 5928 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU493 UT WOS:A1993LU49300076 ER PT J AU AMBERGER, A LEMKIN, PF SONDEREGGER, P BAUER, HC AF AMBERGER, A LEMKIN, PF SONDEREGGER, P BAUER, HC TI ECGF AND HEPARIN DETERMINE DIFFERENTIATION OF CLONED CEREBRAL ENDOTHELIAL-CELLS IN-VITRO SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE CEREBRAL ENDOTHELIAL CELLS; ENDOTHELIAL CELL GROWTH FACTOR; HEPARIN; BLOOD-BRAIN BARRIER; PHENOTYPIC SWITCH ID BLOOD-BRAIN-BARRIER; FIBROBLAST GROWTH-FACTOR; CULTIVATION; PROTEINS; DATABASE; RECEPTOR; BINDING; NEURONS AB Protein expression patterns of morphologically different cloned capillary endothelial cells from porcine and murine brain cortices were examined. Type I cells, grown in medium containing heparin and endothelial cell growth factor (ECGF), exhibited a polygonal, cobblestone appearance and appeared to replicate the cells of the blood-brain barrier endothelium. Type II cells, grown in medium without heparin and ECGF, were elongated and appeared to replicate capillaries in central nervous system tissue. Cells of both phenotypes stained positive by the specific endothelial cell marker Bandeiraea simplicifolia lectin. The expression of alpha smooth-muscle actin (mRNA and protein) was taken as a marker for type II cells. By use of 2-D gel images and the GELLAB II system, a data base was created revealing that two proteins (90 kDa, pI 5.1, and 35 kDa, pI 5.7) were exclusively expressed in type I cells. Furthermore, the synergistic action of ECGF and heparin in respect to the phenotypic determination of cerebral endothelial cells was demonstrated. C1 OAW,INST MOLEC BIOL,BIUROTHSTR 11,A-5020 SALZBURG,AUSTRIA. NCI,MATH BIOL LAB,IMAGE PROC SECT,FREDERICK,MD 21701. UNIV ZURICH,INST BIOCHEM,CH-8006 ZURICH,SWITZERLAND. NR 29 TC 3 Z9 3 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 SEP PY 1993 VL 20 IS 1 BP 33 EP 43 PG 11 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LV695 UT WOS:A1993LV69500003 PM 8251031 ER PT J AU PENNYPACKER, KR DREYER, D HONG, JS MCMILLIAN, MK AF PENNYPACKER, KR DREYER, D HONG, JS MCMILLIAN, MK TI ELEVATED BASAL AP-1 DNA-BINDING ACTIVITY IN DEVELOPING RAT-BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Note DE HIPPOCAMPUS; STRIATUM; HYPOTHALAMUS; C-JUN; TRANSCRIPTION FACTOR; FOS-RELATED ANTIGEN ID C-FOS; STRIATAL NEURONS; SUBSTANTIA-NIGRA; MESSENGER-RNA; EXPRESSION; JUN; INDUCTION; SEIZURES; GENE; PROTEINS AB Nuclear extracts from hippocampi, striata and hypothalami of postnatal day (P) 7 rats contained elevated basal levels of AP-1 DNA binding activity and c-jun protein, which decreased to the low basal levels observed in the adult by P21. In contrast to the AP-1 DNA binding complex in the adult brain, the fos-related antigens were not a major component of the P7 AP-1 DNA binding activity. C1 DURHAM TECH COMMUNITY COLL,DURHAM,NC 27703. RP PENNYPACKER, KR (reprint author), NIEHS,INTEGRAT BIOL LAB,NEUROPHARMACOL SECT,MD E1-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 27 TC 28 Z9 28 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 SEP PY 1993 VL 19 IS 4 BP 349 EP 352 DI 10.1016/0169-328X(93)90138-F PG 4 WC Neurosciences SC Neurosciences & Neurology GA LV995 UT WOS:A1993LV99500014 ER PT J AU MIGLIACCIO, S WETSEL, WC FOX, WM WASHBURN, TF KORACH, KS AF MIGLIACCIO, S WETSEL, WC FOX, WM WASHBURN, TF KORACH, KS TI ENDOGENOUS PROTEIN-KINASE-C ACTIVATION IN OSTEOBLAST-LIKE CELLS MODULATES RESPONSIVENESS TO ESTROGEN AND ESTROGEN-RECEPTOR LEVELS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHORBOL ESTER RECEPTOR; GROWTH-FACTOR RECEPTOR; BREAST-CANCER-CELLS; VITAMIN-D RECEPTOR; GLUCOCORTICOID RECEPTOR; MESSENGER-RNA; RESPONSE ELEMENT; RIBONUCLEIC-ACID; TUMOR PROMOTION; GENE-EXPRESSION AB The osteoblast-like osteosarcoma cell line ROS 17/2.8, which expresses very low levels of estrogen receptor (ER), was stably transfected with the mouse ER in order to more easily evaluate the physiological role of estrogens in bone cell homeostasis. These transfected ROS.SMER 14 cells are highly responsive to estrogenic stimulation at subconfluence, but become refractory to estrogenic stimulation when postconfluency is reached. The purpose of these studies was to determine the mechanisms underlying this loss of responsiveness in these ER stably transfected cells at postconfluence. When proliferative capacity was evaluated by bromodeoxyuridine immunocytochemistry, approximately 70% of the subconfluent cells were actively dividing, whereas none of the postconfluent cells underwent division. Subconfluent cells were found to contain 2500-3000 ER-binding sites/cell, whereas the ER in postconfluent cells was low and often undetectable. Steady state ER mRNA levels were not significantly modified by postconfluency. ER protein levels were also unaffected by confluency status. Since protein kinase-C (PKC) has been reported to influence cell proliferation and steroid hormone receptor binding, PKC activity was measured in sub- and post-confluent cells. Calcium-dependent PKC activity was approximately about 2-fold higher in postconfluent compared to subconfluent cells, whereas no differences were discerned in calcium-independent PKC activity. In an effort to examine the role of PKC in greater detail, postconfluent cells were treated with PKC inhibitors (H-7 or staurosporine) or with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) to down-regulate PKC activity, and changes in ER were evaluated. Inhibition or down-regulation of the PKC activity in postconfluent cells enhanced ER-binding capacity in a dose-dependent manner and estrogen responsiveness of an exogenous reporter gene and of the endogenous alkaline phosphatase, representing an endogenous estrogen-stimulated gene. These data indicate that there is an interaction between the PKC and ER signaling systems in bone cells and that this interaction may be influenced by the proliferative and/or differentiative state of the cells, resulting in modulation of hormone responsiveness. C1 NIEHS, REPROD & DEV TOXICOL LAB, RECEPTOR BIOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NIEHS, CELLULAR & MOLEC PHARMACOL, HORMONE ACT GRP, RES TRIANGLE PK, NC 27709 USA. UNIV ROMA LA SAPIENZA, DEPT EXPTL MED, DIV ENDOCRINOL 2, I-00194 ROME, ITALY. OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X NR 66 TC 41 Z9 41 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1993 VL 7 IS 9 BP 1133 EP 1143 DI 10.1210/me.7.9.1133 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ180 UT WOS:A1993LZ18000004 PM 8247015 ER PT J AU VOGEL, KS AF VOGEL, KS TI DEVELOPMENT OF TROPHIC INTERACTIONS IN THE VERTEBRATE PERIPHERAL NERVOUS-SYSTEM SO MOLECULAR NEUROBIOLOGY LA English DT Review DE NEUROTROPHIN; NEUROTROPHIN RECEPTOR; TROPHIC INTERACTIONS; SENSORY NEURON; SYMPATHETIC NEURON; NEURAL CREST ID GROWTH-FACTOR NGF; NEURAL CREST CELLS; CHICK SYMPATHETIC NEURONS; TYROSINE PROTEIN-KINASE; RETROGRADE AXONAL-TRANSPORT; SUPERIOR CERVICAL-GANGLION; TRK PROTOONCOGENE PRODUCT; ADRENAL CHROMAFFIN CELLS; HUMAN NEUROTROPHIC FACTOR; MESSENGER-RNA EXPRESSION AB During embryogenesis, the neurons of vertebrate sympathetic and sensory ganglia become dependent on neurotrophic factors, derived from their targets, for survival and maintenance of differentiated functions. Many of these interactions are mediated by the neurotrophins NGF, BDNF, and NT3 and the receptor tyrosine kinases encoded by genes of the trk family. Both sympathetic and sensory neurons undergo developmental changes in their responsiveness to NGF, the first neurotrophin to be identified and characterized. Subpopulations of sensory neurons do not require NGF for survival, but respond instead to BDNF or NT3 with enhanced survival. In addition to their classic effects on neuron survival, neurotrophins influence the differentiation and proliferation of neural crest-derived neuronal precursors. In both sympathetic and sensory systems, production of neurotrophins by target cells and expression of neurotrophin receptors by neurons are correlated temporally and spatially with innervation patterns. In vitro, embryonic sympathetic neurons require exposure to environmental cues, such as basic FGF and retinoic acid to acquire neurotrophin-responsiveness; in contrast, embryonic sensory neurons acquire neurotrophin-responsiveness on schedule in the absence of these molecules. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC EMBRYOL SECT, FREDERICK, MD 21702 USA. NR 162 TC 23 Z9 25 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD FAL-WIN PY 1993 VL 7 IS 3-4 BP 363 EP 382 DI 10.1007/BF02769183 PG 20 WC Neurosciences SC Neurosciences & Neurology GA MW526 UT WOS:A1993MW52600010 PM 8179844 ER PT J AU MACKIE, K DEVANE, WA HILLE, B AF MACKIE, K DEVANE, WA HILLE, B TI ANANDAMIDE, AN ENDOGENOUS CANNABINOID, INHIBITS CALCIUM CURRENTS AS A PARTIAL AGONIST IN N18 NEUROBLASTOMA-CELLS SO MOLECULAR PHARMACOLOGY LA English DT Note ID RAT SYMPATHETIC NEURONS; VOLTAGE DEPENDENCE; PERTUSSIS TOXIN; BINDING PROTEIN; CHANNELS; RECEPTOR; RELEASE; BRAIN AB Anandamide (arachidonyl ethanolamide) has been identified as an endogenous ligand of cannabinoid receptors on the basis of its ability to displace H-3-labeled synthetic cannabinoid in a binding assay. One well characterized cellular action of cannabinoids is inhibition of hormonally stimulated adenylyl cyclase. Another action of synthetic cannabinoids is potent, stereospecific, and reversible inhibition of N-type calcium currents (I(Ca)) in the NG108-15 neuroblastoma-glioma cell line via a pertussis toxin (PTX)-sensitive pathway, independently of cAMP metabolism. Here we used the N18 neuroblastoma cell line and the whole-cell voltage-clamp technique to show that anandamide also potently inhibits N-type I(Ca) in a PTX-sensitive fashion. As with the cannabinomimetic aminoalkylindole WIN 55,212-2, inhibition by anandamide was voltage dependent and N-ethylmaleimide sensitive. However, anandamide was less efficacious than either WIN 55,212-2 or the nonclassical cannabinoid CP 55,940. Indeed, anandamide appears to act as a partial agonist at the cannabinoid receptor. Application of WIN 55,212-2 always caused further inhibition Of I(Ca) in cells exposed to a maximally effective concentration of anandamide, and application of anandamide always caused a partial recovery of I(Ca) in cells exposed to a maximally effective concentration of WIN 55,212-2. This partial agonist property of anandamide suggests that, although anandamide inhibits N-type I(Ca) via a PTX-sensitive G protein, its actions as a neuromodulator in the intact animal may be more complex than would be inferred by extrapolating the results of in vivo studies with (-)-DELTA9-tetra-hydrocannabinol or synthetic cannabinoids. C1 UNIV WASHINGTON,SCH MED,DEPT PHYSIOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT ANESTHESIOL,SEATTLE,WA 98195. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Mackie, Kenneth/B-7358-2011 FU NINDS NIH HHS [NS08174, NS01588] NR 26 TC 288 Z9 292 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1993 VL 44 IS 3 BP 498 EP 503 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LY915 UT WOS:A1993LY91500002 PM 8371711 ER PT J AU WONG, LA MAYER, ML AF WONG, LA MAYER, ML TI DIFFERENTIAL MODULATION BY CYCLOTHIAZIDE AND CONCANAVALIN-A OF DESENSITIZATION AT NATIVE ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID-PREFERRING AND KAINATE-PREFERRING GLUTAMATE RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Note ID NOOTROPIC DRUG ANIRACETAM; QUISQUALATE RECEPTORS; STRUCTURAL DETERMINANTS; HIPPOCAMPAL-NEURONS; MUSCLE-FIBERS; HIGH-AFFINITY; CHANNELS; SUBUNIT; CLONING; AMPA AB Concanavalin A, cyclothiazide, and aniracetam, ligands that modulate desensitization at glutamate receptors, were tested for their actions on responses at kainate-preferring receptors in dorsal root ganglion (DRG) neurons and at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring receptors in hippocampal neurons. In DRG neurons concanavalin A blocked desensitization produced by either kainate or 5-chlorowillardiine and strongly potentiated the peak amplitude of responses to both agonists. However, in hippocampal neurons concanavalin A produced only weak potentiation of responses to kainate and 5-chlorowillardiine, and after treatment with lectin responses to 5-chlorowillardiine remained strongly desensitizing. In contrast, cyclothiazide completely blocked desensitization produced by 5-chlorowillardiine in hippocampal neurons and strongly potentiated responses to kainate; the action of aniracetam was similar but much weaker. In DRG neurons cyclothiazide and aniracetam had no effect on desensitization and instead produced weak inhibition of responses to kainate. The different sensitivities of native AMPA- and kainate-preferring glutamate receptors to cyclothiazide and concanavalin A should prove useful for the differentiation of glutamate receptor subtypes in other areas of the central nervous system. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BLDG 49,ROOM 5A78,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013 NR 38 TC 183 Z9 184 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 SEP PY 1993 VL 44 IS 3 BP 504 EP 510 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LY915 UT WOS:A1993LY91500003 PM 7690448 ER PT J AU JOHNS, DG AHLUWALIA, GS COONEY, DA MITSUYA, H DRISCOLL, JS AF JOHNS, DG AHLUWALIA, GS COONEY, DA MITSUYA, H DRISCOLL, JS TI ENHANCED STIMULATION BY RIBAVIRIN OF THE 5'-PHOSPHORYLATION AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY OF PURINE 2'-BETA-FLUORO-2',3'-DIDEOXYNUCLEOSIDES SO MOLECULAR PHARMACOLOGY LA English DT Note ID IMP DEHYDROGENASE STIMULATE; 2',3'-DIDEOXYINOSINE; 2',3'-DIDEOXYADENOSINE; PHOSPHORYLATION; HIV; 2',3'-DIDEOXYNUCLEOSIDES; INFECTIVITY; INHIBITORS; INVITRO AB The purine dideoxynucleosides 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo), 2'-beta-fluoro-2',3'-dideoxyinosine, and 2'-beta-fluoro-2',3'-dideoxyguanosine (2'-beta-F-ddGuo) are active inhibitors of the replication of the human immunodeficiency virus (HIV) in the ATH8 assay system, with 2'-beta-F-ddAdo and 2'-beta-fluoro-2',3'-dideoxyinosine showing activity and potency equivalent to those of their respective parent compounds, 2',3'-dideoxyadenosine (ddAdo) and 2',3'-dideoxyinosine. Because inhibitors of IMP dehydrogenase such as ribavirin and tiazofurin stimulate the 5'-phosphorylation and consequently the anti-HIV activity of the three nonfluorinated parent compounds (ddAdo, 2',3'-dideoxyinosine, and 2',3'-dideoxyguanosine), we have undertaken a study in MOLT-4 cells to determine whether a similar stimulatory effect is observed with their 2'-beta-fluorinated analogs. The 5'-phosphorylation of all the fluoro compounds was found to be greatly enhanced by low levels (10 muM) of either ribavirin or tiazofurin, with the greatest increase being seen with 2'-beta-F-ddAdo, where stimulation of the formation of the 5'-mono-, di-, and triphosphorylated nucleotides was approximately 20-fold, 6-fold, and 5-fold, respectively. These increases were approximately 3-fold greater than the increases seen with the nonfluorinated parent compound ddAdo. In the case of 2'-beta-F-ddGuo, the greatest stimulation (8-fold) was seen in the formation of the 5'-diphosphate. In parallel with the increased phosphorylation of 2'-beta-F-ddAdo and 2'-beta-F-ddGuo, the anti-HIV potency of these two compounds at the 5 mum level was approximately doubled in the presence of ribavirin (5 muM). C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. RP JOHNS, DG (reprint author), NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5B22,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 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 SEP PY 1993 VL 44 IS 3 BP 519 EP 523 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LY915 UT WOS:A1993LY91500005 PM 8371712 ER PT J AU MACARTHUR, L KOLLER, KJ EIDEN, LE AF MACARTHUR, L KOLLER, KJ EIDEN, LE TI ENKEPHALIN GENE-TRANSCRIPTION IN BOVINE CHROMAFFIN CELLS IS REGULATED BY CALCIUM AND PROTEIN KINASE-A SIGNAL-TRANSDUCTION PATHWAYS - IDENTIFICATION OF DNASE I-HYPERSENSITIVE SITES SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROENKEPHALIN MESSENGER-RNA; CYCLIC-AMP; ADRENAL-MEDULLA; CONTAINING PEPTIDES; EXPRESSION; BIOSYNTHESIS; INDUCTION; CAMP; MECHANISMS; SECRETION AB The bovine enkephalin gene is responsive to multiple signaling pathways in primary chromaffin cell cultures. We examined the effects of activation of the calcium and protein kinase A pathways on accumulation of enkephalin peptide and mRNA, gene transcription, and chromatin structure in the 5' region of the gene. We show here that the increase of enkephalin mRNA and peptide after depolarization of chromaffin cells with KCl or activation of adenylate cyclase with forskolin is preceded by an increase in enkephalin gene transcription. Both enkephalin peptide and mRNA were reduced by co-treatment of KCl- or forskolin-stimulated cultures with phorbol esters. Three enhancer sequences that were previously shown to be responsive to calcium, protein kinase A, and phorbol esters in the human gene in vitro were identified in the bovine enkephalin promoter, identifying a potential locus of control for these pathways in vivo. DNase I hypersensitivity mapping identified two tissue-specific sites that are associated with enkephalin gene expression in adrenal medulla and chromaffin cells; site 1 is in the promoter, which contains the three enhancer elements, and site 2 is in the first intron. These results suggest that regulation of the enkephalin gene in primary chromaffin cells by the calcium, protein kinase A, and protein kinase C signaling pathways occurs by modulation of transcription factor activity at several discrete loci on the enkephalin gene. RP MACARTHUR, L (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 45 TC 17 Z9 17 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 SEP PY 1993 VL 44 IS 3 BP 545 EP 551 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LY915 UT WOS:A1993LY91500009 PM 8396715 ER PT J AU STOPPER, H KORBER, C SPENCER, DL KIRCHNER, S CASPARY, WJ SCHIFFMANN, D AF STOPPER, H KORBER, C SPENCER, DL KIRCHNER, S CASPARY, WJ SCHIFFMANN, D TI AN INVESTIGATION OF MICRONUCLEUS AND MUTATION-INDUCTION BY OXAZEPAM IN MAMMALIAN-CELLS SO MUTAGENESIS LA English DT Article ID SUSPECT SPINDLE POISONS; CHINESE-HAMSTER CELLS; MOUSE BONE-MARROW; BENZODIAZEPINE TRANQUILIZERS; PROMOTING ACTIVITY; DIAZEPAM; LIVER; MICE; RAT; CARCINOGENESIS AB The benzodiazepines are a class of drugs that are widely used in the treatment of various psychiatric disorders. One member of this class, oxazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is inconsistent, we investigated the oxazepam-induced formation of micronuclei in Syrian Hamster embryo fibroblast (SHE) cells, human amniotic fluid fibroblast-like (AFFL) cells and L5178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all three celt lines. The time course of micronucleus induction in L5178Y celts showed a maximum at 5 h after treatment, suggesting that the micronuclei were formed in the first mitosis after treatment. Kinetochore staining (CREST-antiserum) revealed the presence of kinetochores in approximately 50% of the micronuclei in all three cell types. This result was further confirmed by in situ hybridization in L5178Y cells and indicates the presence of whole chromosomes or centric fragments as well as acentric fragments in the oxazepam-induced micronuclei. The L5178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used. C1 NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV ROSTOCK,INST ANIM PHYSIOL,CYTOPATHOPHYSIOL UNIT,O-2500 ROSTOCK,GERMANY. RP STOPPER, H (reprint author), UNIV WURZBURG,INST PHARMACOL & TOXICOL,W-8700 WURZBURG,GERMANY. NR 48 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1993 VL 8 IS 5 BP 449 EP 455 DI 10.1093/mutage/8.5.449 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LX712 UT WOS:A1993LX71200012 PM 8231827 ER PT J AU BHATIA, K HUPPI, K SPANGLER, G SIWARSKI, D IYER, R MAGRATH, I AF BHATIA, K HUPPI, K SPANGLER, G SIWARSKI, D IYER, R MAGRATH, I TI POINT MUTATIONS IN THE C-MYC TRANSACTIVATION DOMAIN ARE COMMON IN BURKITTS-LYMPHOMA AND MOUSE PLASMACYTOMAS SO NATURE GENETICS LA English DT Article ID EXPRESSION; GENE; TRANSLOCATION; ACTIVATION; ONCOGENES; APOPTOSIS; CELLS AB We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role. C1 NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892. RP BHATIA, K (reprint author), NCI,PEDIAT BRANCH,CLIN ONCOL PROGRAM,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 20 TC 202 Z9 203 U1 1 U2 4 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 SEP PY 1993 VL 5 IS 1 BP 56 EP 61 DI 10.1038/ng0993-56 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LV565 UT WOS:A1993LV56500016 PM 8220424 ER PT J AU WERTHEIMER, E LU, SP BACKELJAUW, PF DAVENPORT, ML TAYLOR, SI AF WERTHEIMER, E LU, SP BACKELJAUW, PF DAVENPORT, ML TAYLOR, SI TI HOMOZYGOUS DELETION OF THE HUMAN INSULIN-RECEPTOR GENE RESULTS IN LEPRECHAUNISM SO NATURE GENETICS LA English DT Article ID CYSTIC-FIBROSIS; MUTATIONS; CDNA AB Homozygous inactivation of a gene, as is frequently performed to generate mouse models, provides an opportunity to elucidate the role that the gene plays in normal physiology. However, studies of human disease provide direct insight into the effect of inactivating mutations in man. In this investigation, we have identified a one year-old boy from a consanguineous pedigree who is homozygous for deletion of the insulin receptor gene resulting in leprechaunism. Contrary to previous predictions, the complete deletion of the insulin receptor gene is compatible with life. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27399. NR 22 TC 81 Z9 82 U1 0 U2 4 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 SEP PY 1993 VL 5 IS 1 BP 71 EP 73 DI 10.1038/ng0993-71 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA LV565 UT WOS:A1993LV56500019 PM 7693131 ER PT J AU BODDEKE, HWGM HOFFMAN, BJ PALACIOS, JM HOYER, D AF BODDEKE, HWGM HOFFMAN, BJ PALACIOS, JM HOYER, D TI CALCINEURIN INHIBITS DESENSITIZATION OF CLONED RAT 5-HT(1C)RECEPTORS SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE RAT 5-HT(1C)RECEPTORS; A9-CELLS; DESENSITIZATION; CALCINEURIN ID PROTEIN-KINASE-C; XENOPUS OOCYTES; RECEPTORS; RESPONSES; BRAIN; BETA AB Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT1C receptors with serotonin (5-HT) evoked calcium-dependent outward currents of 109 pA in cells clamped at -50 mV. Pretreatment with the protein kinase C (PKC) activator phorbol myristic acetate (PMA) reduced the 5-HT-induced current amplitude by 46% of the control value. Inclusion of inositol triphosphate (IP3) in the pipette solution induced an outward current of 84 pA. The IP3-induced response was not affected by 60 min pretreatment with PMA. In the presence of the PKC antagonist calphostin C, 60 min treatment with PMA (10(-6) mol/1) reduced the 5-HT response only by 8%. In cells preincubated with PMA, injection of the calcium/calmodulin dependent serine proteinphosphatase calcineurin gradually increased the 5-HT-induced responses by 34%. In A9 cells which were incubated 24 h with the 5-HT1C receptor agonist meta chlorophenylpiperazine hydrochloride (mCPP), 5-HT-induced responses were reduced by 23% of the vehicle pretreated control value. Injection of calcineurin in mCPP treated cells enhanced the 5-HT-induced response by 24%. The results suggest that in A9 cells rat 5-HT1c receptors are desensitized after phosphorylation by PKC. This desensitization can be counteracted by calcineurin-induced dephosphorylation. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. LABS ALMIRALL SA,E-08024 BARCELONA,SPAIN. RP BODDEKE, HWGM (reprint author), SANDOZ LTD,PRECLIN RES,CH-4002 BASEL,SWITZERLAND. OI Hoyer, Daniel/0000-0002-1405-7089 NR 14 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD SEP PY 1993 VL 348 IS 3 BP 221 EP 224 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LW887 UT WOS:A1993LW88700001 PM 7694158 ER PT J AU INGRAM, DK WIENER, HL CHACHICH, ME LONG, JM HENGEMIHLE, J GUPTA, M AF INGRAM, DK WIENER, HL CHACHICH, ME LONG, JM HENGEMIHLE, J GUPTA, M TI CHRONIC TREATMENT OF AGED MICE WITH L-DEPRENYL PRODUCES MARKED STRIATAL MAO-B INHIBITION BUT NO BENEFICIAL-EFFECTS ON SURVIVAL, MOTOR-PERFORMANCE, OR NIGRAL LIPOFUSCIN ACCUMULATION SO NEUROBIOLOGY OF AGING LA English DT Article DE AGING; LIFE-SPAN; CATECHOLAMINES; DOPAMINE; BEHAVIOR; NEUROANATOMY; SUBSTANTIA-NIGRA; PARKINSONS DISEASE ID ADVANCED PARKINSONS-DISEASE; MONOAMINE-OXIDASE; LONG-TERM; LIFE-SPAN; MALE-RATS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; SUPEROXIDE-DISMUTASE; ALZHEIMERS TYPE; BIOLOGICAL AGE; DOPAMINE AB Male C57BL/6J mice were provided 1-deprenyl (at 0, 0.5 mg/kg or 1.0 mg/kg per day) in their drinking water beginning at 18 months of age. A battery of motor tests, including open-field, tightrope, rotorod, inclined screen, runwheel, and rotodrum tests, was administered before treatment and then 6 months later at 24 months of age. A subsample of mice was retested again at 27 months of age. An untreated group of 9-month-old mice served as young controls. Deprenyl treatment reduced striatal MAO-B activity by up to 60% after 6 months on treatment but had no significant effects on striatal catecholamine levels. No significant effects of deprenyl treatment were observed on body weight, fluid intake, or survival of the mice. Chronic deprenyl treatment also did not affect motor performance in any test, except rotodrum performance at 27 months of age, which was significantly better in the 1.0 mg/kg group treated group compared to controls. No age or deprenyl effects were observed with respect to cell counts in the substantia nigra. However, nigral cells containing lipofuscin increased with age, but this neurohistochemical parameter was also unaffected by deprenyl treatment. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,DEPT PHARMACEUT SCI,JAMAICA,NY 11439. UNIV LOUISVILLE,HLTH SCI CTR,DEPT ANAT SCI & NEUROBIOL,LOUISVILLE,KY 40292. RP INGRAM, DK (reprint author), NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NINDS NIH HHS [NS24291] NR 57 TC 32 Z9 32 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP-OCT PY 1993 VL 14 IS 5 BP 431 EP 440 DI 10.1016/0197-4580(93)90101-G PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA LW589 UT WOS:A1993LW58900004 PM 8247225 ER PT J AU RUTTLEDGE, MH NAROD, SA DUMANSKI, JP PARRY, DM ELDRIDGE, R WERTELECKI, W PARBOOSINGH, J FAUCHER, MC LENOIR, GM COLLINS, VP NORDENSKJOLD, M ROULEAU, GA AF RUTTLEDGE, MH NAROD, SA DUMANSKI, JP PARRY, DM ELDRIDGE, R WERTELECKI, W PARBOOSINGH, J FAUCHER, MC LENOIR, GM COLLINS, VP NORDENSKJOLD, M ROULEAU, GA TI PRESYMPTOMATIC DIAGNOSIS FOR NEUROFIBROMATOSIS-2 WITH CHROMOSOME-22 MARKERS SO NEUROLOGY LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; SUBUNIT NF-H; GENETIC-LINKAGE; LENS OPACITIES; TYPE-2; NEUROMAS; IDENTIFICATION; POLYMORPHISM; ASSOCIATION; LOCUS AB Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by multiple tumors of the central nervous system, predominantly bilateral vestibular schwannomas. The gene for NF2 is located in the chromosomal region 22q12 between the loci D22S1 and D22S28. We have performed genetic linkage analysis on 13 NF2 families with a total of nine polymorphic DNA markers, including five which we have recently mapped to this region. Two loci, D22S32 and NEFH, are linked to the NF2 locus at 0% recombination (lod scores of 6.03 and 4.28, respectively). By multipoint linkage analysis, we assign the NF2 gene to an interval of 7 cM, between the loci D22S212 and D22S28. We have used this set of nine markers to construct chromosome 22 haplotypes for the 82 at-risk individuals in this pedigree set. It has been possible to determine, with a high degree of certainty, the carrier status of 70 (85%) of these at-risk individuals. Risk prediction was possible in every case where DNA was available from both parents. Fifty-three of the 70 (76%) informative individuals were assigned decreased risks of being carriers. The use of chromosome 22 probes for risk assessment should result in a greatly reduced number of individuals who require periodic screening for NF2. C1 KAROLINSKA HOSP,DEPT CLIN GENET,S-10401 STOCKHOLM 60,SWEDEN. LUDWIG INST CANC RES,CLIN GRP,STOCKHOLM,SWEDEN. INT AGCY RES CANC,MECHANISMS CARCINOGENESIS UNIT,F-69372 LYON,FRANCE. UNIV SO ALABAMA,DEPT MED GENET,MOBILE,AL 36688. MCGILL UNIV,MONTREAL GEN HOSP,CTR HUMAN GENET,MONTREAL H3G 1A4,QUEBEC,CANADA. MCGILL UNIV,MONTREAL GEN HOSP,DEPT NEUROL,MONTREAL H3G 1A4,QUEBEC,CANADA. NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. SAHLGRENS UNIV HOSP,DEPT PATHOL 1,S-41345 GOTHENBURG,SWEDEN. NR 30 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1993 VL 43 IS 9 BP 1753 EP 1760 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA LY058 UT WOS:A1993LY05800023 PM 8414026 ER PT J AU TRACER, HL LOH, YP AF TRACER, HL LOH, YP TI THE EFFECT OF SALT-LOADING ON CORTICOTROPIN-RELEASING HORMONE AND ARGININE-VASOPRESSIN MESSENGER-RNA LEVELS IN THE MOUSE HYPOTHALAMUS - A QUANTITATIVE IN-SITU HYBRIDIZATION ANALYSIS SO NEUROPEPTIDES LA English DT Article ID RAT ANTERIOR-PITUITARY; PROOPIOMELANOCORTIN GENE-EXPRESSION; PROTEIN KINASE-C; ADRENOCORTICOTROPIN SECRETION; ACTH RELEASE; CELLS; OXYTOCIN; RESPONSES; NUCLEI; HISTOCHEMISTRY AB Previously, we showed that during salt-loading in mice there was an acute rise in plasma ACTH levels after 2 days followed by a transient decrease after 4 and 9 days. Pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary increased after 2 days and returned to normal thereafter. In this study, changes in hypothalamic CRH and AVP mRNA levels during salt-loading were investigated using quantitative in situ hybridization histochemistry. CRH mRNA was expressed only in the paraventricular nucleus (PVN), while AVP mRNA was expressed in both the supraoptic (SON) and paraventricular nuclei. CRH mRNA levels were unchanged after 2 days salt-loading, but declined to 77% of control levels after 9 days. AVP mRNA levels rose to 260% and 634% of control levels in the SON, and to 352% and 522% of control levels in the PVN, after 2 and 9 days salt-loading, respectively. These data suggest a major role of AVP in the acute stimulation of ACTH secretion and POMC mRNA levels seen after 2 days salt-loading. Densitization of AVP receptors at the corticotroph level and a centrally mediated inhibition of CRH release may account for the decrease of ACTH secretion and POMC mRNA levels in the anterior pituitary with prolonged salt-loading. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,RM 2A21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 41 TC 7 Z9 7 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD SEP PY 1993 VL 25 IS 3 BP 161 EP 167 DI 10.1016/0143-4179(93)90098-U PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA LW720 UT WOS:A1993LW72000001 PM 8247254 ER PT J AU RAPAPORT, MH WOLKOWITZ, O KELSOE, JR PATO, C KONICKI, PE PICKAR, D AF RAPAPORT, MH WOLKOWITZ, O KELSOE, JR PATO, C KONICKI, PE PICKAR, D TI BENEFICIAL-EFFECTS OF NALMEFENE AUGMENTATION IN NEUROLEPTIC-STABILIZED SCHIZOPHRENIC-PATIENTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE SCHIZOPHRENIA; OPIATES; NEUROLEPTICS; OPIATE ANTAGONISTS; PSYCHOTROPIC TREATMENT ID PERFORMANCE LIQUID-CHROMATOGRAPHY; WORLD-HEALTH-ORGANIZATION; BETA-ENDORPHIN; ELECTROCHEMICAL DETECTION; CSF LEVELS; PLASMA AB It was postulated that chronic blockade of the opioid system in neuroleptic-stabilized schizophrenic patients would have a beneficial behavioral effect. Eleven neuroleptic-stabilized psychotic inpatients received augmentation with nalmefene for an average of 36.7 days in a double-blind placebo-controlled study. The patients exhibited significant reductions in Bunney-Hamburg psychosis ratings and the Brief Psychiatric Rating Scale thinking disturbance subscale during the augmentation period. This study presents preliminary data supporting the hypothesis that chronic augmentation of neuroleptic-stabilized schizophrenic patients with opiate antagonists is beneficial. C1 VET ADM MED CTR,PSYCHIAT SERV,SAN DIEGO,CA 92161. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02912. CASE WESTERN RESERVE UNIV,DEPT PSYCHIAT,CLEVELAND,OH 44106. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP RAPAPORT, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT,0655,LA JOLLA,CA 92093, USA. NR 32 TC 12 Z9 13 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 SEP PY 1993 VL 9 IS 2 BP 111 EP 115 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LU681 UT WOS:A1993LU68100003 PM 8105790 ER PT J AU CARPENTER, WT BENES, F CARLSSON, A TAMMINGA, C WEINBERGER, DR GRACE, AA AF CARPENTER, WT BENES, F CARLSSON, A TAMMINGA, C WEINBERGER, DR GRACE, AA TI INTERACTIVE DISCUSSION OF SCHIZOPHRENIA SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,CATONSVILLE,MD 21228. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. UNIV GOTEBORG,DEPT PHARMACOL,S-41390 GOTHENBURG,SWEDEN. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV PITTSBURGH,CTR NEUROSCI,DEPT BEHAV NEUROSCI & PSYCHIAT,PITTSBURGH,PA 15260. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S53 EP S54 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800113 ER PT J AU CHROUSOS, GP AF CHROUSOS, GP TI INTERACTIONS BETWEEN THE LIMBIC-HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND THE IMMUNE INFLAMMATORY RESPONSE SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S39 EP S40 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800084 ER PT J AU GOODWIN, FK AF GOODWIN, FK TI MECHANISMS AND MANAGEMENT OF TREATMENT-RESISTANT AFFECTIVE-DISORDERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S19 EP S19 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800040 ER PT J AU HOFFMAN, BJ AF HOFFMAN, BJ TI MOLECULAR-BIOLOGY OF MONOAMINE AND GLYCINE TRANSPORTERS - MECHANISMS OF REGULATING NEUROTRANSMISSION SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S33 EP S33 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800071 ER PT J AU JACOBSEN, FM AF JACOBSEN, FM TI LOW-DOSE VALPROATE TREATMENT OF CYCLOTHYMIA, RABID CYCLING BIPOLAR-II DISORDER, AND PREMENSTRUAL-SYNDROME SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 TRANSCULTURAL MENTAL HLTH INST,WASHINGTON,DC 20036. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1993 VL 9 IS 2 SU S BP S55 EP S56 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800116 ER PT J AU KALOGERAS, KT GLOWA, JR SMITH, MA BOWEN, H PESSIN, AB LEE, S DEDHIA, PM CHROUSOS, GP GOLD, PW AF KALOGERAS, KT GLOWA, JR SMITH, MA BOWEN, H PESSIN, AB LEE, S DEDHIA, PM CHROUSOS, GP GOLD, PW TI HYPOTHALAMIC-PITUITARY-ADRENAL AXIS RESPONSES TO BENZODIAZEPINE WITHDRAWAL - POTENTIAL ROLE OF CRH IN THE WITHDRAWAL SYNDROME SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S76 EP S76 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800159 ER PT J AU LESCH, KP AULAKH, CS WOLOZIN, BL RIEDERER, P MURPHY, DL AF LESCH, KP AULAKH, CS WOLOZIN, BL RIEDERER, P MURPHY, DL TI NOREPINEPHRINE, SEROTONIN AND VESICULAR MONOAMINE TRANSPORTER IN DEPRESSION AND BIPOLAR DISORDER - EXPRESSION DURING LONG-TERM ANTIDEPRESSANT TREATMENT SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY. NIMH,CTR CLIN,LCS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1993 VL 9 IS 2 SU S BP S34 EP S35 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800074 ER PT J AU MASTORAKOS, G GAUDET, SJ PATCHEV, VK BOUZAS, EA CHADER, GJ CHROUSOS, GP AF MASTORAKOS, G GAUDET, SJ PATCHEV, VK BOUZAS, EA CHADER, GJ CHROUSOS, GP TI STUDIES IN ARYLALKYLAMINE (SEROTONIN) AND ARYLAMINE N-ACETYLTRANSFERASE (NAT) ACTIVITIES IN INFLAMMATORY DISEASE-SUSCEPTIBLE LEWIS AND DISEASE-RESISTANT FISCHER RATS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NICHHD,DEB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 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 SEP PY 1993 VL 9 IS 2 SU S BP S148 EP S148 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800327 ER PT J AU MURPHY, DL AULAKH, C PIGOTT, T GRADY, T BROOCKS, A BAGDY, G GARRICK, N AF MURPHY, DL AULAKH, C PIGOTT, T GRADY, T BROOCKS, A BAGDY, G GARRICK, N TI PARALLEL INVESTIGATIONS OF SEROTONERGIC MODULATION OF NEUROENDOCRINE EFFECTS IN HUMAN, NONHUMAN-PRIMATES AND RODENTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S24 EP S24 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800050 ER PT J AU NOWAK, G PAUL, IA LAYER, RT POPIK, P SKOLNICK, P AF NOWAK, G PAUL, IA LAYER, RT POPIK, P SKOLNICK, P TI ADAPTATION OF THE N-METHYL-D-ASPARATE (NMDA) RECEPTOR COMPLEX FOLLOWING CHRONIC ANTIDEPRESSANTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S38 EP S38 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800081 ER PT J AU OSTROWSKI, NL LOLAIT, SJ YOUNG, WS AF OSTROWSKI, NL LOLAIT, SJ YOUNG, WS TI VASOPRESSIN-V1A AND VASOPRESSIN-V2 RECEPTOR MESSENGER-RIBONUCLEIC-ACID LOCALIZATION IN RAT-BRAIN, KIDNEY AND LIVER SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S145 EP S145 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800321 ER PT J AU POST, RM PAZZAGLIA, PJ KETTER, TA GEORGE, MS MARANGELL, L AF POST, RM PAZZAGLIA, PJ KETTER, TA GEORGE, MS MARANGELL, L TI CARBAMAZEPINE AND NIMODIPINE IN REFRACTORY BIPOLAR ILLNESS - EFFICACY AND MECHANISMS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S17 EP S18 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800036 ER PT J AU RUBINOW, DR SU, TP AF RUBINOW, DR SU, TP TI NEUROBEHAVIORAL EFFECTS OF ANDROGENIC AND ANABOLIC-STEROIDS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S5 EP S6 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800012 ER PT J AU SMITH, MA MAKINO, S KVETNANSKY, R POST, RM AF SMITH, MA MAKINO, S KVETNANSKY, R POST, RM TI STRESS-INDUCED CHANGES IN NEUROTROPHIC FACTOR MESSENGER-RNA LEVELS IN THE RAT HIPPOCAMPUS SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S177 EP S177 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800393 ER PT J AU SMITH, MA BERRY, R CLARK, M POST, RM AF SMITH, MA BERRY, R CLARK, M POST, RM TI CORTICOTROPIN-RELEASING FACTOR IS COEXPRESSED WITH GABA IN THE DENTATE GYRUS FOLLOWING AMYGDALA KINDLING SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1993 VL 9 IS 2 SU S BP S141 EP S141 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LV408 UT WOS:A1993LV40800311 ER PT J AU WYMAN, JF ELSWICK, RK ORY, MG WILSON, MS FANTL, JA AF WYMAN, JF ELSWICK, RK ORY, MG WILSON, MS FANTL, JA TI INFLUENCE OF FUNCTIONAL, UROLOGICAL, AND ENVIRONMENTAL CHARACTERISTICS ON URINARY-INCONTINENCE IN COMMUNITY-DWELLING OLDER WOMEN SO NURSING RESEARCH LA English DT Article ID HOME AB The purpose of this study was to explore the relationships of functional, urological, and environmental characteristics to the frequency of urinary incontinence in 131 community-dwelling older women. Subjects with detrusor instability with or without concomitant genuine stress incontinence had significantly more impaired physical functioning, slower gait speeds, smaller bladder capacities, and less ability to delay voiding than subjects with genuine stress incontinence alone. Age, distance to toilet used most, and toilet-gait speed explained 17% of the variance in incontinence alone. Younger age, slower mobility, and a shorter distance to reach the toilet were associated with a higher frequency of incontinence. Physical functional status and urological characteristics, including urodynamic diagnosis, did not predict incontinence severity. These findings confirm, in part, the commonly held assumption that mobility and the environment influence urinary incontinence. C1 VIRGINIA COMMONWEALTH UNIV,SCH BASIC SCI,DEPT BIOSTAT,RICHMOND,VA 23284. NIA,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,SCH MED,DEPT SURG,RICHMOND,VA 23284. VIRGINIA COMMONWEALTH UNIV,SCH MED,DEPT OBSTET & GYNECOL,RICHMOND,VA 23284. RP WYMAN, JF (reprint author), VIRGINIA COMMONWEALTH UNIV,SCH NURSING,DEPT COMMUNITY & PSYCHIAT NURSING,RICHMOND,VA 23284, USA. FU NIA NIH HHS [AG05170] NR 18 TC 13 Z9 15 U1 1 U2 1 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0029-6562 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 1993 VL 42 IS 5 BP 270 EP 275 PG 6 WC Nursing SC Nursing GA MD479 UT WOS:A1993MD47900004 PM 8415039 ER PT J AU NAGEY, DA BAILEYJONES, C HERMAN, AA AF NAGEY, DA BAILEYJONES, C HERMAN, AA TI RANDOMIZED COMPARISON OF HOME UTERINE ACTIVITY MONITORING AND ROUTINE CARE IN PATIENTS DISCHARGED AFTER TREATMENT FOR PRETERM LABOR SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PROSPECTIVE RANDOM TRIAL; INCREASED RISK; BIRTH; PREVENTION; PREGNANCIES AB Objective: To determine whether home uterine activity monitoring reduces the likelihood of preterm birth in women successfully treated for preterm labor in their current pregnancies. Methods: Women between 20-34 weeks' gestation who had been treated successfully for preterm labor were solicited to participate in a randomized clinical trial of home uterine activity monitoring versus routine high-risk care. The sample size of 56 was based on power calculations using the results of earlier investigators. Twenty-eight women were randomized to home uterine activity monitoring and 29 were assigned to the type of care appropriate for women discharged after hospitalization for parenteral treatment of preterm labor. One of the routine-care subjects was lost to follow-up. The two groups were comparable in distribution for race, insurance status, multiple gestation, marital status, gestational age at beginning of the study, and incidence of prior preterm birth. Results: The 28 women receiving routine care had a 54% incidence of preterm birth, whereas the incidence was 57% in monitored women (relative risk 1.08, 95% confidence interval 0.6-1.9; P = .79). The incidences of delivery before 32 weeks and 34 weeks also were unaffected by the intervention. Conclusion: Home uterine activity monitoring is not effective in reducing the likelihood of preterm delivery in patients successfully treated for preterm labor in their current pregnancies. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. RP NAGEY, DA (reprint author), UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 11 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1993 VL 82 IS 3 BP 319 EP 323 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LU534 UT WOS:A1993LU53400001 PM 8355927 ER PT J AU LEONE, A FLATOW, U VANHOUTTE, K STEEG, PS AF LEONE, A FLATOW, U VANHOUTTE, K STEEG, PS TI TRANSFECTION OF HUMAN NM23-H1 INTO THE HUMAN MDA-MB-435 BREAST-CARCINOMA CELL-LINE - EFFECTS ON TUMOR METASTATIC POTENTIAL, COLONIZATION AND ENZYMATIC-ACTIVITY SO ONCOGENE LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; YEAST SCHIZOSACCHAROMYCES-POMBE; GTP-BINDING PROTEINS; COLORECTAL-CARCINOMA; DISEASE PROGRESSION; GOOD PROGNOSIS; EXPRESSION; GENE; CANCER; DROSOPHILA AB We report the phenotypic effects of transfection of human nm23-H1 cDNA into the human MDA-MB-435 breast carcinoma cell line. Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines. Reductions in tumor metastatic potential in vivo were accompanied by decreased colonization in soft agar and an altered colonization response to transforming growth factor beta in vitro. Total nucleoside diphosphate kinase activity, an enzymatic activity possessed by the Nm23 family, was not directly correlated with Nm23-H1 expression levels or suppression of metastatic potential in all cases examined. The data establish that nm23-H1 has functional suppressive effects on the tumor metastatic potential of a human breast carcinoma cell line, and suggest that it may regulate signal responsiveness in the colonization response. C1 NIH,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. FREDERICK CANC RES & DEV FACIL,FREDERICK,MD 21702. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 52 TC 281 Z9 291 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1993 VL 8 IS 9 BP 2325 EP 2333 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LT368 UT WOS:A1993LT36800002 PM 8395676 ER PT J AU CUADRADO, A BRUDER, JT HEIDARAN, MA APP, H RAPP, UR AARONSON, SA AF CUADRADO, A BRUDER, JT HEIDARAN, MA APP, H RAPP, UR AARONSON, SA TI H-RAS AND RAF-1 COOPERATE IN TRANSFORMATION OF NIH3T3 FIBROBLASTS SO ONCOGENE LA English DT Article ID PROTEIN-KINASE-C; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION; ONCOGENE PRODUCTS; GROWTH-FACTOR; 3T3 CELLS; EXPRESSION; ACTIVATION; GENE; HETEROGENEITY AB We examined the effect of overexpression of growth factor-regulated second messenger enzymes, alone and in combination, on transformation of NIH3T3 cells. Signal transducers included phospholipase C-gamma (PLC-gamma), protein kinase C-gamma (PKC-gamma), and two proto-oncogenes, c-H-ras and c-raf-1. Three of these proteins, PLC-gamma PKC-gamma and Raf-1, did not transform NIH3T3 cells alone or in combination. c-H-ras, which under its own promoter control has low transforming activity, also did not cooperate with PLC-gamma or PKC-gamma. In contrast, the combination of normal or oncogenic p21 H-Ras with the Raf-I kinase dramatically increased transformation efficiency. The level of Ras protein required for transformation was reduced in Raf-1 co-transfectants, implying that, at low levels of p21 Ras, p74 Raf-I is rate limiting. As transformation by Ras depends on jun-mediated transcriptional events, we also examined H-ras and c-raf-1 cooperation in transcriptional transactivation of TPA-responsive element (TRE)-dependent reporters. Like the H-ras/c-raf-1 cooperation in transformation, we observed this synergistic stimulation of TRE-dependent transcription. This pathway for transformation and transcriptional activation by increased levels of normal Ras and Raf may be important in tumors that show overexpression but lack mutationally activated forms of these two proto-oncogenes. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. SUGEN INC,REDWOOD CITY,CA 94063. NR 55 TC 38 Z9 38 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1993 VL 8 IS 9 BP 2443 EP 2448 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LT368 UT WOS:A1993LT36800015 PM 8361757 ER PT J AU HARVEY, M SANDS, AT WEISS, RS HEGI, ME WISEMAN, RW PANTAZIS, P GIOVANELLA, BC TAINSKY, MA BRADLEY, A DONEHOWER, LA AF HARVEY, M SANDS, AT WEISS, RS HEGI, ME WISEMAN, RW PANTAZIS, P GIOVANELLA, BC TAINSKY, MA BRADLEY, A DONEHOWER, LA TI IN-VITRO GROWTH-CHARACTERISTICS OF EMBRYO FIBROBLASTS ISOLATED FROM P53-DEFICIENT MICE SO ONCOGENE LA English DT Article ID WILD-TYPE P53; TUMOR-ANTIGEN; GENE-PRODUCT; T-ANTIGEN; DNA; CELLS; PROTEIN; IMMORTALIZATION; TRANSFORMATION; EXPRESSION AB Fibroblast cultures were derived from mouse embryos containing either one (p53+/-) or two (p53-/-) inactivated p53 alleles and compared to normal embryo fibroblasts for a number of growth parameters. Early passage p53-deficient embryo fibroblasts (p53-/-) divided faster than normal embryo fibroblasts, achieved higher confluent densities, and had a higher fraction of division-competent cells under conditions of low cell density. Flow cytometry studies of early passage embryo fibroblasts showed that the percent of p53-deficient cells in G0/G1 was lower than in normal cells, consistent with the argument that p53 mediates a GI block. When p53-deficient and normal cells were passaged for long periods of time, the homozygote (p53-/-) fibroblasts grew at a high rate for over 50 passages and never entered a non-growing senescent phase characteristic of the heterozygote (p53+/-) and normal (p53+/+) cells. The p53-deficient fibroblasts were genetically unstable during passaging, with the p53-/- cells showing a high degree of aneuploidy and the p53+/- cells displaying a moderate level of chromosomal abnormalities by passage 25. Surprisingly, the heterozygote cells lost their single wild type allele very early during culturing and in spite of this loss most heterozygote lines entered into senescence. We conclude that the loss of p53 by itself is insufficient to confer immortality on a cell, but does confer a growth advantage. Taken together, the findings confirm that the absence of p53 promotes genomic instability, which in turn may result in genetic alterations which directly produce immortality. C1 BAYLOR COLL MED,DEPT MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. STEHLIN FDN CANC RES,HOUSTON,TX 77002. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. UNIV TEXAS,M D ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. RI Hegi, Monika/O-4796-2015 OI Hegi, Monika/0000-0003-0855-6495 FU NCI NIH HHS [CA54897] NR 46 TC 461 Z9 465 U1 4 U2 10 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1993 VL 8 IS 9 BP 2457 EP 2467 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LT368 UT WOS:A1993LT36800017 PM 8103211 ER PT J AU STERN, MH SOULIER, J ROSENZWAJG, M NAKAHARA, K CANKIKLAIN, N AURIAS, A SIGAUX, F KIRSCH, IR AF STERN, MH SOULIER, J ROSENZWAJG, M NAKAHARA, K CANKIKLAIN, N AURIAS, A SIGAUX, F KIRSCH, IR TI MTCP-1 - A NOVEL GENE ON THE HUMAN-CHROMOSOME XQ28 TRANSLOCATED TO THE T-CELL RECEPTOR ALPHA/DELTA LOCUS IN MATURE T-CELL PROLIFERATIONS SO ONCOGENE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; VARIABLE REGION GENES; ATAXIA-TELANGIECTASIA; MOLECULAR ANALYSIS; CHAIN LOCUS; BREAKPOINT; PATIENT; INVERSION; SEQUENCES; RECOMBINATION AB T-cell lymphoproliferative diseases are often associated with recurrent chromosomal translocations involving T cell receptor genes (TCR) and genes that are thought to play a role in the pathogenesis of these diseases. Whereas numerous such genes have already been identified in acute T cell leukemias, no candidate gene has vet been identified to play a role in the heterogeneous group of T cell proliferations with a mature phenotype. We here report the molecular cloning of two examples of the rare but recurrent t(X;14) translocation. The first translocation was associated with a benign clonal proliferation in an ataxia telangiectasia patient and the second with a T cell prolymphocytic leukemia. Both translocations implicated the TCR alpha/delta locus and a common breakpoint region on chromosome Xq28. A previously unidentified gene, abnormally transcribed in both T cell proliferations, was characterized in the immediate proximity of the breakpoints. This Xq28 gene has no homology with known sequences, uses a complex alternative splicing pattern and demonstrates two short open reading frames. This gene, named MTCP-1 (Mature T Cell Proliferation-1) is the first candidate gene potentially involved in the leukemogenic process of mature T cell proliferations. C1 NATL CANC INST,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. SLUZBA ZA MED GENET,LJUBLJANA,SLOVENIA. INST CURIE,CNRS,URA620,F-75005 PARIS,FRANCE. RP STERN, MH (reprint author), HOP ST LOUIS,HEMATOL MOLEC LAB,F-75475 PARIS,FRANCE. RI Stern, Marc-Henri/A-2728-2011 OI Stern, Marc-Henri/0000-0002-8100-2272 NR 41 TC 121 Z9 123 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1993 VL 8 IS 9 BP 2475 EP 2483 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LT368 UT WOS:A1993LT36800019 PM 8361760 ER PT J AU WHITCUP, SM DESMET, MD RUBIN, BI PALESTINE, AG MARTIN, DF BURNIER, M CHAN, CC NUSSENBLATT, RB AF WHITCUP, SM DESMET, MD RUBIN, BI PALESTINE, AG MARTIN, DF BURNIER, M CHAN, CC NUSSENBLATT, RB TI INTRAOCULAR LYMPHOMA - CLINICAL AND HISTOPATHOLOGIC DIAGNOSIS SO OPHTHALMOLOGY LA English DT Article ID RETICULUM-CELL SARCOMA; CENTRAL NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; MALIGNANT-LYMPHOMA; VITREOUS CELLS; THERAPY; MANAGEMENT; RADIATION; BIOPSY AB Background: Intraocular lymphoma is associated with significant morbidity and mortality, but early diagnosis and treatment may improve prognosis. Methods: The diagnostic features of 12 cases of intraocular lymphoma diagnosed at the National Eye Institute between 1984 and 1992 were retrospectively reviewed. Results: A pathologic diagnosis of large B-cell lymphoma was made on vitrectomy specimens in ten patients, cerebral spinal fluid in one, and on an enucleation specimen in one. The mean time from onset of symptoms to diagnosis was 21.4 months (range, 1-66 months). All 12 patients were given a final diagnosis of non-Hodgkin's lymphoma of the central nervous system (NHL-CNS), based on the epidemiology, pathology, and clinical course of their tumors. Although an initial vitrectomy was negative for malignant cells in three of ten patients, a repeat vitrectomy specimen subsequently showed intraocular lymphoma. Results of examination of the cerebrospinal fluid (CSF) showed malignant cells in 5 of 11 patients, although malignant cells were only identified after repeat examination of additional samples of CSF in three of these patients. Malignant cells often are difficult to identify, and an experienced cytopathologist was critical in making the correct diagnosis. In addition, corticosteroids are lympholytic to the lymphoma cells, and they appeared to decrease the viability of tumor cells obtained in samples of vitreous and CSF. Conclusion: The prompt, appropriate handling of specimens and review by an experienced cytopathologist are critical to the diagnosis of intraocular lymphoma. Malignant cells often are present in the cerebral spinal fluid at the time that ocular lymphoma is diagnosed. Nevertheless, multiple vitrectomies and lumbar punctures may be necessary before the correct diagnosis is made. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N 202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 34 TC 178 Z9 191 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1993 VL 100 IS 9 BP 1399 EP 1406 PG 8 WC Ophthalmology SC Ophthalmology GA LX192 UT WOS:A1993LX19200029 PM 8371930 ER PT J AU WU, AJ SHIP, JA AF WU, AJ SHIP, JA TI A CHARACTERIZATION OF MAJOR SALIVARY-GLAND FLOW-RATES IN THE PRESENCE OF MEDICATIONS AND SYSTEMIC-DISEASES SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID DIFFERENT AGE-GROUPS; XEROSTOMIA; SYMPTOMS AB The purpose of this study was to characterize the effects of medications and systemic diseases on major salivary gland flow rates. Unstimulated and 2% citrate-stimulated parotid and submandibular salivas were collected from 293 subjects of the oral physiology component of the Baltimore Longitudinal Study of Aging. The influence of the number of medications and diseases on salivary flow rates was determined by separate one-way ANOVA tests. There was an overall decrease in both parotid and submandibular flow rates with increasing numbers of medications and systemic diseases. However, this was significant (p < 0.05) only for unstimulated submandibular flow rates (with increasing numbers of systemic diseases) and stimulated submandibular flow rates (with increasing numbers of systemic diseases and medications). Unstimulated flow rates rapidly approached zero with increasing numbers of medications and diseases. These results suggest that the submandibular gland may be more sensitive to physiologic permutations than the parotid gland. In addition, individuals being treated for multiple systemic diseases and taking numerous medications may be more susceptible to salivary hypofunction. RP WU, AJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 31 TC 67 Z9 71 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD SEP PY 1993 VL 76 IS 3 BP 301 EP 306 DI 10.1016/0030-4220(93)90258-6 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LX162 UT WOS:A1993LX16200011 PM 8378045 ER PT J AU JOHNSTONE, PAS SINDELAR, WF AF JOHNSTONE, PAS SINDELAR, WF TI LYMPH-NODE INVOLVEMENT AND PANCREATIC RESECTION - CORRELATION WITH PROGNOSIS AND LOCAL DISEASE-CONTROL IN A CLINICAL-TRIAL SO PANCREAS LA English DT Article DE SURGERY; RADIOTHERAPY; INTRAOPERATIVE RADIOTHERAPY; LYMPH NODES; PROGNOSIS ID FACTORS INFLUENCING SURVIVAL; DUCTAL ADENOCARCINOMA; CANCER; PANCREATICODUODENECTOMY; EXPERIENCE; CARCINOMA; HEAD AB In a prospectively randomized trial evaluating pancreatic resection with adjuvant radiotherapy (intraoperative radiotherapy [IORT] vs. external beam radiotherapy [EBRT]), lymph nodal involvement was examined and correlated with outcome. Twenty-six patients underwent pancreatic resection and received either IORT or EBRT (Stages II-IV). Patients who were stage I received surgery alone. Regional nodal metastases were present in 15 of 26 (57%) patients. Seven patients suffered treatment-related mortality. Survival, mortality, and morbidity were unaffected by the type of radiotherapy. The survival of patients with negative nodes (median survival 24 months, range 10 to > 109) appeared superior to the survival of patients with nodal involvement (median survival 11.5 months; range 4-39). Even in patients with locally advanced disease extending into extrapancreatic tissues, two node-negative patients appeared to survive longer (12 and 53 months) than 10 node-positive patients with similarly extensive local disease (median survival 11.5 months: range 4-39). Local disease control, however, appeared to be independent of nodal involvement, with eventual local recurrences in 6 of 8 node-negative patients and in 4 of 7 node-positive patients who were evaluable for local disease control by autopsy or by antemortem laparotomy. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 14 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD SEP PY 1993 VL 8 IS 5 BP 535 EP 539 DI 10.1097/00006676-199309000-00001 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV717 UT WOS:A1993LV71700001 PM 8302788 ER PT J AU JACOBSON, JD TRUOG, WE BENJAMIN, DR AF JACOBSON, JD TRUOG, WE BENJAMIN, DR TI INCREASED EXPRESSION OF HUMAN-LEUKOCYTE ANTIGEN-DR ON PULMONARY MACROPHAGES IN BRONCHOPULMONARY DYSPLASIA SO PEDIATRIC RESEARCH LA English DT Article ID HUMAN ALVEOLAR MACROPHAGE; IMMUNE INTERFERON; FC-RECEPTOR; IA-ANTIGEN; CELL-LINE; GAMMA; BRONCHIOLITIS; FIBROSIS; PRODUCTS; ANTIBODY AB We used an immunoperoxidase method to examine the expression of the immune activation marker HLA-DR on pulmonary tissue obtained at autopsy from 14 patients dying of bronchopulmonary dysplasia. Controls consisted of 16 age-matched, sex-matched children dying of noncardiac, nonrespiratory, noninfectious illnesses or as a result of motor vehicle accidents. We did not observe aberrant expression of HLA-DR on pulmonary endothelial cells. Positive staining appeared exclusively on macrophages. We quantitated the expression of antigen by counting the number of positive macrophages and total macrophages/monocytes per high power field. Bronchopulmonary dysplasia patients displayed significantly greater numbers of both positive and total macrophages compared with the control group (p < 0.05). The percent positive macrophages also was significantly higher in the bronchopulmonary dysplasia patients (p < 0.005). We also examined a group of patients dying with infant respiratory distress syndrome. There was no significant difference in number of total macrophages in this group compared with age-matched controls. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,DEPT PEDIAT,DIV NEONATAL & RESP DIS,SEATTLE,WA 98195. CHILDRENS HOSP & MED CTR,DEPT PATHOL,DIV LABS,SEATTLE,WA 98105. FU NCRR NIH HHS [S07 RRR02673.41] NR 28 TC 4 Z9 4 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 SEP PY 1993 VL 34 IS 3 BP 341 EP 344 DI 10.1203/00006450-199309000-00020 PG 4 WC Pediatrics SC Pediatrics GA LV039 UT WOS:A1993LV03900020 PM 8134177 ER PT J AU KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR CORDERO, JF KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HD SIMON, PR FALK, H MILLER, RW ROGAN, W JACKSON, RJ AF KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR CORDERO, JF KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HD SIMON, PR FALK, H MILLER, RW ROGAN, W JACKSON, RJ TI USE OF CHLORAL HYDRATE FOR SEDATION IN CHILDREN SO PEDIATRICS LA English DT Editorial Material ID STRAND BREAKS; LIVER INVIVO; TRICHLOROETHYLENE; MOUSE; ANEUPLOIDY; INDUCTION; COHORT; TOXICITY; EXPOSURE; CANCER C1 AMER MED ASSOC,CHICAGO,IL 60610. CTR DIS CONTROL & PREVENT,ATLANTA,GA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. RI Goldman, Lynn/D-5372-2012 NR 35 TC 62 Z9 63 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1993 VL 92 IS 3 BP 471 EP 473 PG 3 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500028 ER PT J AU MERENSTEIN, GB CASSADY, G ESCOBEDO, M FANAROFF, AA FELDMAN, BH FERNBACH, SA KIRKPATRICK, BV KLEINMAN, LI LIGHT, IJ ALLEN, A DOOLEY, SL KENNER, C ROWLEY, D WRIGHT, LL KRUMMEL, TM OH, W AF MERENSTEIN, GB CASSADY, G ESCOBEDO, M FANAROFF, AA FELDMAN, BH FERNBACH, SA KIRKPATRICK, BV KLEINMAN, LI LIGHT, IJ ALLEN, A DOOLEY, SL KENNER, C ROWLEY, D WRIGHT, LL KRUMMEL, TM OH, W TI ROUTINE EVALUATION OF BLOOD-PRESSURE, HEMATOCRIT, AND GLUCOSE IN NEWBORNS SO PEDIATRICS LA English DT Editorial Material ID HYPOGLYCEMIA; DEFINITION; INFANTS C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA. NIH,BETHESDA,MD 20892. NR 11 TC 42 Z9 42 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1993 VL 92 IS 3 BP 474 EP 476 PG 3 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500029 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G DAUM, RS LEDBETTER, EO AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G DAUM, RS LEDBETTER, EO TI HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES - RECOMMENDATIONS FOR IMMUNIZATION WITH RECENTLY AND PREVIOUSLY LICENSED VACCINES SO PEDIATRICS LA English DT Editorial Material ID INFANT RHESUS-MONKEYS; ANTIBODY-RESPONSES; CHILDREN; EFFICACY; IMMUNOGENICITY; POLYSACCHARIDE; DISEASE; INFECTION; TRIAL C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. RI Steele, Russell/A-6075-2011 NR 33 TC 8 Z9 9 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1993 VL 92 IS 3 BP 480 EP 488 PG 9 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500031 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G TI USE OF RIBAVIRIN IN THE TREATMENT OF RESPIRATORY SYNCYTIAL VIRUS-INFECTION SO PEDIATRICS LA English DT Editorial Material ID CHILDREN; INFANTS; AEROSOL C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RI Steele, Russell/A-6075-2011 NR 17 TC 54 Z9 54 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1993 VL 92 IS 3 BP 501 EP 504 PG 4 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500037 ER PT J AU XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB AF XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB TI DIFFERENTIAL BINDING OF OPIOID-PEPTIDES AND OTHER DRUGS TO 2 SUBTYPES OF OPIOID DELTA-NCX BINDING-SITES IN MOUSE-BRAIN - FURTHER EVIDENCE FOR DELTA-RECEPTOR HETEROGENEITY SO PEPTIDES LA English DT Article DE OPIOID PEPTIDES; OPIOID BINDING SITES; MOUSE BRAIN; DELTA RECEPTOR HETEROGENEITY ID GUINEA-PIG BRAIN; POSITRON EMISSION TOMOGRAPHY; BETA-ADRENERGIC RECEPTORS; HIGHLY SELECTIVE LIGAND; HIGH-AFFINITY; RAT-BRAIN; QUANTITATIVE-ANALYSIS; OPIATE RECEPTORS; G-PROTEIN; PSEUDOALLOSTERIC MODULATION AB Research into the functional role of the opioid delta receptor has intensified with the recent in vivo identification of delta receptor subtypes, termed delta1 and delta2, which mediate antinociception in the mouse. A variety of data also support the hypothesis of an opioid receptor complex composed of distinct, yet interacting, mu, delta, and perhaps kappa binding sites. This model postulates two classes of delta binding sites: a delta binding site not associated with the opioid receptor complex, termed the delta(ncx) site, and a delta site associated with the receptor complex, termed the delta(cx) site. A major purpose of this study was to clarify the relationship between the delta(ncx) binding sites and the delta1 and delta2 receptors. Mouse brain membranes were depleted of mu sites by pretreatment with the site-directed acylating agent, BIT, and the delta(ncx) binding sites were labeled with [H-3][D-Ala2,D-Leu5]enkephalin. Binding surface analysis readily resolved two binding sites (delta(ncx-1) and delta(ncx-2)) in the absence and presence of 100 mM NaCl. Control experiments with guanine nucleotides and the ligand-selectivity analysis indicated that the two sites were not two states of a single receptor. Pretreatment of membranes with DALCE, but not [Cys4]deltorphin, decreased [H-3][D-Ala2,D-Leu5]enkephalin and [H-3][D-Ser2,Thr6]enkephalin binding. Ligand-selectivity analysis of the two binding sites suggested that neither delta(ncx) binding site had the characteristics expected of the delta2 receptor, and that the delta(ncx-1) site, but not the delta(ncx-2) site, was synonymous with the delta1 receptor. Moreover, our finding that the racemic nonpeptide delta agonist, BW373U86, had high affinity at and selectivity for the delta(ncx-2) site suggests that this site may be a novel delta receptor that mediates some of the effects of BW373U86. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 78 TC 40 Z9 40 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP-OCT PY 1993 VL 14 IS 5 BP 893 EP 907 DI 10.1016/0196-9781(93)90064-N PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA LZ783 UT WOS:A1993LZ78300005 PM 8284266 ER PT J AU CLARK, DA DAY, R SEIDAH, N MOODY, TW CUTTITTA, F DAVIS, TP AF CLARK, DA DAY, R SEIDAH, N MOODY, TW CUTTITTA, F DAVIS, TP TI PROTEASE INHIBITORS SUPPRESS IN-VITRO GROWTH OF HUMAN SMALL-CELL LUNG-CANCER SO PEPTIDES LA English DT Article DE PROTEASE INHIBITORS; SMALL CELL LUNG CANCER; GASTRIN-RELEASING PEPTIDE; PEPTIDE PROCESSING; PROHORMONE CONVERTASE-1 AND CONVERTASE-2; GROWTH REGULATION ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; C-MYC EXPRESSION; MEDULLARY CHROMAFFIN GRANULES; RECEPTOR ANTAGONISTS; BETA-ENDORPHIN; MESSENGER-RNAS; LINES; PROTEINS; GENE AB The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell lines was investigated. In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI-H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated by Western blot analysis. NCI-H345 cells, when treated with BBI (100 mug/ml), also showed highly significant decreases of mRNA for PC1 and PC2 of about 50%. These data suggest that proteases serve an important role in the growth regulation of SCLC and that inhibitors of these proteases may be potent suppressors of SCLC growth at the level of the gene. C1 UNIV ARIZONA, COLL MED, DEPT PHARMACOL, TUCSON, AZ 85724 USA. CLIN RES INST MONTREAL, MONTREAL H2W 1R7, QUEBEC, CANADA. USN HOSP, BETHESDA, MD 20814 USA. UNIV ARIZONA, ARIZONA CANC CTR, TUCSON, AZ 85724 USA. USN, NCI, MED ONCOL BRANCH, BETHESDA, MD 20814 USA. GEORGE WASHINGTON UNIV, MED CTR, DEPT BIOCHEM, WASHINGTON, DC 20037 USA. RI Seidah, Nabil/I-3596-2013; davis, thomas/F-3244-2015 OI Seidah, Nabil/0000-0001-6503-9342; davis, thomas/0000-0001-8465-4973 FU NCI NIH HHS [CA-53477, CA-44869]; NIDDK NIH HHS [DK-36289] NR 50 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD SEP-OCT PY 1993 VL 14 IS 5 BP 1021 EP 1028 DI 10.1016/0196-9781(93)90081-Q PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA LZ783 UT WOS:A1993LZ78300022 PM 7506831 ER PT J AU BRAUN, AR JASKIW, GE VLADAR, K SEXTON, RH KOLACHANA, BS WEINBERGER, DR AF BRAUN, AR JASKIW, GE VLADAR, K SEXTON, RH KOLACHANA, BS WEINBERGER, DR TI EFFECTS OF IBOTENIC ACID LESION OF THE MEDIAL PREFRONTAL CORTEX ON DOPAMINE AGONIST-RELATED BEHAVIORS IN THE RAT SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE DOPAMINE; DOPAMINE AGONISTS; MEDIAL PREFRONTAL CORTEX; PRESYNAPTIC; POSTSYNAPTIC; D1 RECEPTOR; D2 RECEPTOR; RAT; BEHAVIOR; STEREOTYPIC BEHAVIOR; LOCOMOTION; GROOMING; OPEN-FIELD BEHAVIOR; BEHAVIORAL DISORGANIZATION ID NUCLEUS-ACCUMBENS; RECEPTOR AGONISTS; FRONTAL-CORTEX; AMPHETAMINE RESPONSES; CORTICAL-LESIONS; SELECTIVE D-1; ANIMAL-MODELS; BRAIN; APOMORPHINE; D1 AB Behavioral responses to apomorphine and to the selective D1 and D2 dopamine receptor agonists SK&F38393 and quinpirole were evaluated in rats following ibotenic acid (IA) or sham lesion of the medial prefrontal cortex (MPFC). IA-lesioned rats showed an increased responsiveness to the postsynaptic effects of all of the dopamine agonists. Patterns of the responses to the selective agonists administered alone and in combination suggest that these effects might be due to selective increases in the sensitivity of postsynaptic D1 receptor-associated mechanisms. In addition, IA-lesioned rats pretreated with saline were hyperactive in comparison to sham-lesioned rats when animals were exposed to a novel open field, but spontaneous motor activity did not differ between these two groups when animals were pretreated with low doses (0.03 mg/kg) of quinpirole. The fact that hyperreactivity observed in lesioned animals is inhibited by a dose of quinpirole that is felt to act presynaptically, selectively attenuating endogenous dopaminergic tone, suggests that effects of the MPFC lesion may be mediated presynaptically as well. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PSYCHIAT,CLEVELAND,OH 44106. NIMH,CTR NEUROSCI ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP BRAUN, AR (reprint author), NIDOCD,VOICE SPEECH & LANGUAGE BRANCH,BLDG 10,ROOM 5D38,BETHESDA,MD 20892, USA. NR 51 TC 39 Z9 39 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 SEP PY 1993 VL 46 IS 1 BP 51 EP 60 DI 10.1016/0091-3057(93)90316-L PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA LY413 UT WOS:A1993LY41300009 PM 7902985 ER PT J AU DABESTANI, R SIK, RH DAVIS, DG DUBAY, G CHIGNELL, CF AF DABESTANI, R SIK, RH DAVIS, DG DUBAY, G CHIGNELL, CF TI SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS .18. INDOMETHACIN SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET MOLECULAR-OXYGEN AB The photochemistry, photophysics, and photosensitization (Type I and II) of indomethacin (IN) (N-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid) has been studied in a variety of solvents using NMR, high performance liquid chromatography-mass spectroscopy, transient spectroscopy, electron paramagnetic resonance in conjunction with the spin trapping technique, and the direct detection of singlet molecular oxygen (O-1(2)) luminescence. Photodecomposition of IN (lambda(ex) > 330 nm) in degassed or air-saturated benzene proceeds rapidly to yield a major (2; N-[p-chlorobenzoyl]-5-methoxy-2-methyl-3-methylene-indoline) and a minor (3; N-[p-chlorobenzoyl]-5-methoxy-2,3-dimethyl-indole) decarboxylated product and a minor indoline (5; 1-en-5-methoxy-2-methyl-3-methylene-indoline), which is formed by loss of the p-chlorobenzoyl moiety. In air-saturated solvents two minor oxidized products 4 (N-[p-chlorobenzoyl]-5-methoxy-2-methylindol-3-aldehyde) and 6 (5-methoxy-2-methyl-indole-3-aldehyde) are also formed. When photolysis was carried out in O-18(2)-saturated benzene, the oxidized products 4 and 6 contained O-18, indicating that oxidation was mediated by dissolved oxygen in the solvent. In more polar solvents such as acetonitrile or ethanol, photodecomposition is extremely slow and inefficient. Phosphorescence of IN at 77 K shows strong solvent dependence and its emission is greatly reduced as polarity of solvent is increased. Flash excitation of IN in degassed ethanol or acetonitrile produces no transients. A weak transient is observed at 375 nm in degassed benzene, which is not quenched by oxygen. Irradiation of IN (lambda(ex) > 325 nm) in N2-gassed C6H6 in the presence of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) results in the trapping of two carbon-centered radicals by DMPO. One adduct was identified as DMPO/.COC6H4-P-Cl, while the other was probably derived from a radical formed during IN decarboxylation. In air-saturated benzene, (hydro) peroxyl and alkoxyl radical adducts of DMPO are observed. A very weak luminescence signal from O-1(2) at 1268 nm is observed initially upon irradiation (lambda(ex) = 325 nm) of IN in air-saturated benzene or chloroform. The intensity of this O-1(2) signal increases as irradiation is continued suggesting that the enhancement in O-1(2) yield is due to photoproduct(s). Accordingly, when 2 and 3 were tested directly, 2 was found to be a much better sensitizer of O-1(2) than IN. In air-saturated ethanol or acetonitrile no IN O-1(2) luminescence is detected even on continuous irradiation. The inability of IN to cause phototoxicity may be related to its photostability in polar solvents, coupled with the low yield of active oxygen species (O-1(2), O2-) upon UV irradiation. C1 DUKE UNIV,DEPT CHEM,DURHAM,NC 27706. RP DABESTANI, R (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP PY 1993 VL 58 IS 3 BP 367 EP 373 DI 10.1111/j.1751-1097.1993.tb09576.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LZ209 UT WOS:A1993LZ20900010 PM 8234471 ER PT J AU SMITH, BD DAVIDSON, RA GREEN, RL AF SMITH, BD DAVIDSON, RA GREEN, RL TI EFFECTS OF CAFFEINE AND GENDER ON PHYSIOLOGY AND PERFORMANCE - FURTHER TESTS OF A BIOBEHAVIORAL MODEL SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE AROUSAL; CAFFEINE; GENDER; ELECTRODERMAL ACTIVITY; RECALL; BIOBEHAVIORAL MODEL; HABITUATION ID BILATERAL ELECTRODERMAL ACTIVITY; SEX-DIFFERENCES; SENSATION-SEEKING; SKIN-CONDUCTANCE; BLOOD-PRESSURE; MEMORY; EXTRAVERSION; HABITUATION; MOOD; WITHDRAWAL AB The present study extended testing of our biobehavioral model describing the effects of arousal and caffeine to include an examination of gender differences and their interactions with habitual and acute caffeine ingestion. Males and females selected as high or low habitual caffeine users were randomly assigned to receive either caffeine or a placebo and exposed to novel and repetitive recall tasks and to simple auditory stimuli. Electrodermal activity and recall task performance were recorded. The four major factors examined, including habitual caffeine use, acute ingestion, gender, and stimulus novelty, affected behavior, physiology, or both. Results showed that habitual caffeine usage systematically affected tonic arousal (skin conductance level) and improved recall task performance. Acute caffeine ingestion increased phasic arousal (skin conductance response amplitude) and reduced habituation rates. Gender interacted with other factors to significantly affect both tonic and phasic arousal, and females performed better than males on the recall tasks. These results were partially supportive of the theoretical model, and further work is needed to examine the interactions of acute and chronic caffeine intake with gender and novelty. C1 NIH,BETHESDA,MD 20892. RP SMITH, BD (reprint author), UNIV MARYLAND,DEPT PSYCHOL,COLL PK,MD 20742, USA. NR 51 TC 14 Z9 14 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD SEP PY 1993 VL 54 IS 3 BP 415 EP 422 DI 10.1016/0031-9384(93)90229-9 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA LT513 UT WOS:A1993LT51300001 PM 8415931 ER PT J AU CHMURNY, GN PAUKSTELIS, JV ALVARADO, AB MCGUIRE, MT SNADER, KM MUSCHIK, GM HILTON, BD AF CHMURNY, GN PAUKSTELIS, JV ALVARADO, AB MCGUIRE, MT SNADER, KM MUSCHIK, GM HILTON, BD TI NMR STRUCTURE DETERMINATION AND INTRAMOLECULAR TRANSESTERIFICATION OF 4 DIACETYL TAXININES WHICH CO-ELUTE WITH TAXOL OBTAINED FROM TAXUS X MEDIA HICKSII NEEDLES SO PHYTOCHEMISTRY LA English DT Article DE TAXUS X MEDIA; TAXACEAE; YEW; NEEDLES; NMR; TAXININES; TAXOL; TRANSESTERIFICATION ID BREVIFOLIA; CHINENSIS; TAXANES; SPECTROSCOPY; ASSIGNMENTS; BACCATA AB The isolation of taxol from Taxus x. media Hicksii includes four taxinines which co-elute and interfere with HPLC analyses of taxol. Their structures: 1,9alpha-dihydroxy-2alpha,10beta-diacetoxy-5alpha-cinnamatetaxa-4(20),11-diene-13-one; 1,10beta-dihydroxy-2alpha,9alpha-diacetoxy-5alpha-cinnamatetaxa-4(20),11-diene-13-one;2alpha,9alpha-dihydroxy-10beta,13alpha-diacetoxy-5alpha-cinnamatetaxa-4(20),11-diene and; 2alpha,10beta-dihydroxy-9alpha,13alpha-diacetoxy-5alpha-cinnamatetaxa-4(20),11-diene, have been determined by 1D(H-1, C-13) and 2D(DQCOSY, TOCSY, HMQC, HMBC and TROESY) NMR spectroscopy. Transacetylation between 10beta and 9alpha on the baccatin core has been documented to occur in CDCl3 and CD3OD at 27-degrees. Interatomic distances were obtained from TROESY build-up curves of the first compound and were compared to those obtained from a computer minimized structure. C1 NCI,DCT,DTP,NPB,FREDERICK,MD 21702. RP CHMURNY, GN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,CHEM SYNTH & ANAL LAB,PROGRAM RESOURCES,FREDERICK,MD 21702, USA. NR 28 TC 18 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD SEP PY 1993 VL 34 IS 2 BP 477 EP 483 DI 10.1016/0031-9422(93)80034-P PG 7 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA LY984 UT WOS:A1993LY98400032 ER PT J AU DIJOUX, MG LAVAUD, C MASSIOT, G LEMENOLIVIER, L SHEELEY, DM AF DIJOUX, MG LAVAUD, C MASSIOT, G LEMENOLIVIER, L SHEELEY, DM TI A SAPONIN FROM LEAVES OF APHLOIA-MADAGASCARIENSIS SO PHYTOCHEMISTRY LA English DT Article DE APHLOIA-MADAGASCARIENSIS; FLACOURTIACEAE; TRITERPENE SAPONINS; 6-BETA,23-DIHYDROXYTORMENTIC ACID ID TRITERPENOIDS AB Two triterpene saponins were isolated from the leaves of Aphloia madagascariensis. One compound was new and the structure was elucidated as 28-O-beta-D-glucopyranosyl 6beta,23-dihydroxytormentic acid by means of high field 1D and 2D NMR and mass spectroscopy. The other compound is 28-O-beta-D-glucopyranosyl 6beta-hydroxy-tormentic acid. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP DIJOUX, MG (reprint author), FAC PHARM REIMS,PHARMACOGNOSIE LAB,CNRS,URA 492,51 RUE COGNACQ JAY,F-51096 REIMS,FRANCE. NR 8 TC 7 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD SEP PY 1993 VL 34 IS 2 BP 497 EP 499 DI 10.1016/0031-9422(93)80037-S PG 3 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA LY984 UT WOS:A1993LY98400035 ER PT J AU MUSHEGIAN, AR KOONIN, EV AF MUSHEGIAN, AR KOONIN, EV TI THE PROPOSED PLANT CONNEXIN IS A PROTEIN KINASE-LIKE PROTEIN SO PLANT CELL LA English DT Letter ID FAMILY C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL,BETHESDA,MD 20892. RP MUSHEGIAN, AR (reprint author), UNIV KENTUCKY,DEPT PLANT PATHOL,LEXINGTON,KY 40546, USA. OI Mushegian, Arcady/0000-0002-6809-9225 NR 9 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD SEP PY 1993 VL 5 IS 9 BP 998 EP 999 DI 10.1105/tpc.5.9.998 PG 2 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA LY034 UT WOS:A1993LY03400002 PM 8400879 ER PT J AU GREENWALD, P AF GREENWALD, P TI NCI CANCER PREVENTION AND CONTROL RESEARCH SO PREVENTIVE MEDICINE LA English DT Article ID BREAST-CANCER; DIETARY FIBER; EPIDEMIOLOGIC EVIDENCE; ALCOHOL-CONSUMPTION; BETA-CAROTENE; CHEMOPREVENTION RESEARCH; TAMOXIFEN THERAPY; TRACE-ELEMENTS; CLINICAL-TRIAL; UNITED-STATES RP NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. NR 87 TC 20 Z9 20 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 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 1993 VL 22 IS 5 BP 642 EP 660 DI 10.1006/pmed.1993.1058 PG 19 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LZ781 UT WOS:A1993LZ78100002 PM 8234204 ER PT J AU BARILLARI, G GENDELMAN, R GALLO, RC ENSOLI, B AF BARILLARI, G GENDELMAN, R GALLO, RC ENSOLI, B TI THE TAT PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, A GROWTH-FACTOR FOR AIDS KAPOSI-SARCOMA AND CYTOKINE-ACTIVATED VASCULAR CELLS, INDUCES ADHESION OF THE SAME CELL-TYPES BY USING INTEGRIN RECEPTORS RECOGNIZING THE RGD AMINO-ACID-SEQUENCE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; LONG-TERM CULTURE; CD4+ T-CELLS; HTLV-III; FIBRONECTIN; EXPRESSION; MODULATION; GENE; PATHOGENESIS; RETROVIRUS AB Spindle-shaped cells of vascular origin are the probable tumor cells of Kaposi sarcoma (KS). These cells, derived from patients with KS and AIDS, proliferate in response to extracellular Tat protein of human immunodeficiency virus type 1. Normal vascular cells, believed to be the progenitors of AIDS-KS cells, acquire spindle morphology and become responsive to the mitogenic effect of Tat after culture with inflammatory cytokines. Such cytokines are increased in human immunodeficiency virus type 1-infected people, suggesting that immune stimulation (rather than immune deficiency) is a component of AIDS-KS pathogenesis. Here we show that (i) Tat promotes adhesion of AIDS-KS and normal vascular cells; (ii) adhesion of normal vascular cells to Tat is induced by exposure of the cells to the same cytokines; (iii) adhesion is associated with the amino acid sequence RGD of Tat through a specific interaction with the integrin receptors alpha5beta1 and alpha(v)beta3, although it is augmented by the basic region; and (iv) the expression of both integrins is increased by the same cytokines that promote these cells to acquire spindle morphology and become responsive to the adhesion and growth effects of Tat. The results also suggest that RGD-recognizing integrins mediate the vascular cell-growth-promoting effect of Tat. C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 43 TC 319 Z9 320 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1993 VL 90 IS 17 BP 7941 EP 7945 DI 10.1073/pnas.90.17.7941 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400008 PM 7690138 ER PT J AU SHU, LM QI, CF SCHLOM, J KASHMIRI, SVS AF SHU, LM QI, CF SCHLOM, J KASHMIRI, SVS TI SECRETION OF A SINGLE-GENE-ENCODED IMMUNOGLOBULIN FROM MYELOMA CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SINGLE-CHAIN ANTIBODY; ANTITUMOR ANTIBODY; EUKARYOTIC EXPRESSION; HUMAN PAN-CARCINOMA ANTIGEN ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; HUMAN IGG1 ANTIBODY; CHAIN FV; BIOLOGICAL PROPERTIES; TUMOR-CELLS; B72.3; GENERATION; ANTIGEN; LYSIS AB We describe construction of a single gene encoding a single-chain immunoglobulin-like molecule. This single-gene approach circumvents inefficiencies inherent in delivering two genes into a mammalian cell and in the assembly of a functional immunoglobulin molecule. It would also facilitate ex vivo transfection of cells for gene-therapy protocols. SP2/0 murine myeloma cells transfected with the single gene SGDELTAC(L)C(H)1 expressed a single-chain protein, SCDELTAC(L)C(H)1, comprising almost-equal-to 60 kDa of the anti-carcinoma monoclonal antibody (mAb) CC49. The single-chain protein consisted of the heavy- and light-chain variable (V(H) and V(L)) domains of the mAb covalently joined through a short linker peptide, while the carboxyl end of the V(L) domain was linked to the amino terminus of the human gamma1 Fc region through the hinge region. The single-chain protein assembled into a dimeric molecule, termed SCADELTAC(L)C(H)1, of almost-equal-to 120 kDa and was secreted into the tissue culture fluid. SDS/PAGE analysis of the secreted immunoglobulin purified by protein G affinity chromatography confirmed the size of the molecule. The native mAb CC49 and SCADELTAC(L)C(H)1 of CC49 showed similar binding to the tumor-associated glycoprotein TAG-72, and the chimeric mAb CC49 and SCADELTAC(L)C(H)1 showed similar cytotoxic activity. This single-gene construct approach provides a way of generating an immunoglobulin-like molecule which retains the specificity, binding properties, and cytolytic activity of the chimeric mAb CC49. The immunoglobulin-like molecule SCADELTAC(L)C(H)1 is potentially a therapeutic and diagnostic reagent against a range of human carcinomas. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 21 TC 57 Z9 60 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 SEP 1 PY 1993 VL 90 IS 17 BP 7995 EP 7999 DI 10.1073/pnas.90.17.7995 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400019 PM 8367454 ER PT J AU LISZIEWICZ, J SUN, D SMYTHE, J LUSSO, P LORI, F LOUIE, A MARKHAM, P ROSSI, J REITZ, M GALLO, RC AF LISZIEWICZ, J SUN, D SMYTHE, J LUSSO, P LORI, F LOUIE, A MARKHAM, P ROSSI, J REITZ, M GALLO, RC TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION BY REGULATED EXPRESSION OF A POLYMERIC TAT ACTIVATION RESPONSE RNA DECOY AS A STRATEGY FOR GENE-THERAPY IN AIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; TAT; RIBOZYME ID CELL; PROTEIN; SEQUENCES; BINDING; MODEL; SAFE; LINE; LTR AB We are investigating a strategy for somatic gene therapy to treat human immunodeficiency virus type 1 (HIV-1) infection by intracellular expression of an RNA decoy and a ribozyme. The RNA decoy, consisting of polymeric Tat activation response elements (TARs), is designed to compete for Tat binding in an equilibrium with viral TAR RNA, thereby inhibiting viral replication. The expression of polymeric TAR is regulated by the HIV long terminal repeat (LTR) and transcriptional activation is dependent on the presence of HIV Tat. Our initial studies indicated that plasmids expressing up to 50 tandem copies of TAR RNA (50TAR) inhibited tat-mediated gene expression by >90% in a transient transfection assay. A HIV LTR-driven 50TAR construct was subcloned into a replication-defective retroviral vector to ensure high-efficiency gene transfer into T lymphocytes. In addition, a gag RNA-specific ribozyme gene was introduced into the 50TAR containing retroviral vector to enhance the inhibitory effect of the construct (designated TAR-Rib). A human T-cell line (Molt3) was infected (transduced) with the TAR-Rib recombinant retrovirus and challenged with either HIV-1 or simian immunodeficiency virus (SIV). HIV-1 replication was inhibited by 99% in the TAR-Rib-transduced T cells and was maintained over a 14-month period, suggesting that this antiviral strategy represses the formation of escape mutants. Interestingly, the TAR-Rib also inhibited SIV replication in transduced T cells, which suggests that polymeric TAR is a general inhibitor of primate lentiviruses; therefore, the macaque model could be used for further in vivo testing of this antiviral gene therapy strategy. C1 ADV BIOSCI LABS INC,KENSINGTON,MD 20895. CITY HOPE NATL MED CTR,BECKMAN RES INT,DUARTE,CA 91010. RP LISZIEWICZ, J (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 114 Z9 117 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1993 VL 90 IS 17 BP 8000 EP 8004 DI 10.1073/pnas.90.17.8000 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400020 PM 8367455 ER PT J AU GOSSE, ME PADMANABHAN, A FLEISCHMANN, RD GOTTESMAN, MM AF GOSSE, ME PADMANABHAN, A FLEISCHMANN, RD GOTTESMAN, MM TI EXPRESSION OF CHINESE-HAMSTER CAMP-DEPENDENT PROTEIN-KINASE IN ESCHERICHIA-COLI RESULTS IN GROWTH-INHIBITION OF BACTERIAL-CELLS - A MODEL SYSTEM FOR THE RAPID SCREENING OF MUTANT TYPE-I REGULATORY SUBUNITS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID-SEQUENCE; DNA TOPOISOMERASE-I; RNA CAPPING ENZYME; CATALYTIC SUBUNIT; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; CDNA; FORM AB The regulatory and catalytic subunits of cAMP-dependent protein kinase (PKA) were coexpressed within the same bacterial cell using a polycistronic bacterial T7 expression vector encoding Chinese hamster cDNAs for the type I regulatory (RI) and catalytic alpha (Calpha) subunits of PKA. Basal expression of active RI/Calpha holoenzyme in the BL21(DE3) strain of Escherichia coli caused severe growth inhibition resulting in extremely small colony size. Several lines of evidence demonstrate that this growth inhibition requires active PKA subunits and cAMP: Ot this phenotype is dependent on cAMP since it is not seen in a strain lacking adenylyl cyclase activity, but the growth rate of these transformants is slower when exogenous cAMP is added; (ii) normal growth occurs when wild-type RI cDNA is replaced by a mutant RI cDNA encoding a RI protein with reduced cAMP binding; and (iii) the growth-inhibited phenotype of the transformed BL21(DE3) cells requires soluble, active Calpha protein. Holoenzyme expressed in bacteria is activated by cAMP, which stimulates phosphorylation of an endogenous 50-kDa protein that is missing in four host mutants selected for normal growth after transformation with PKA holoenzyme. A mutant RI cDNA library was generated by PCR random mutagenesis and screened by polycistronic expression in BL21(DE3) cells. The RI cDNA sequence from one revertant has base-pair substitutions creating two amino acid substitutions within the cAMP binding sites. The coexpression of the RI/Calpha subunits in BL21(DE3) bacterial cells provides a system for rapidly selecting mutations in the RI subunits of PKA. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892. NR 36 TC 8 Z9 8 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 SEP 1 PY 1993 VL 90 IS 17 BP 8159 EP 8163 DI 10.1073/pnas.90.17.8159 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400053 PM 8396261 ER PT J AU FRANK, EG HAUSER, J LEVINE, AS WOODGATE, R AF FRANK, EG HAUSER, J LEVINE, AS WOODGATE, R TI TARGETING OF THE UMUD, UMUD', AND MUCA' MUTAGENESIS PROTEINS TO DNA BY RECA PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AFFINITY CHROMATOGRAPHY; CHEMILUMINESCENT IMMUNOASSAY; DNA MOBILITY-SHIFT ASSAY; NUCLEOPROTEIN COMPLEXES ID ULTRAVIOLET-LIGHT MUTAGENESIS; ESCHERICHIA-COLI; SOS MUTAGENESIS; UV MUTAGENESIS; POLYMERASE-III; CLEAVAGE; REPAIR; DEFICIENT; MUTATIONS; MUTANTS AB In addition to its critical role in genetic recombination, the Escherichia coli RecA protein plays a pivotal role in SOS-induced mutagenesis. This role can be separated genetically into three steps: (i) derepression of the SOS regulon by mediating the posttranslational cleavage of the LexA repressor, (ii) activation of UmuD'-like proteins by mediating cleavage of the UmuD-like proteins, and (iii) a direct step, possibly to interact with and to target the Umu-like mutagenesis proteins to lesions in DNA. We have analyzed RecA's third role biochemically using protein affinity chromatography and an agarose-based DNA mobility-shift assay. RecA730 protein from a crude cell extract was specifically retained on UmuD and UmuD' protein affinity columns, suggesting that these proteins physically interact. Normally, neither UmuD nor UmuD' shows any affinity for DNA. In the presence of RecA protein, however, UmuD and UmuD' were targeted to DNA. RecA1730 protein, which is defective for UmuD' but proficient for MucA'-promoted mutagenesis, showed a dramatically reduced capacity to target UmuD' to DNA but was able to target a significant portion of MucA' to DNA. These data support the suggestion that the direct role of RecA protein in SOS-induced mutagenesis is to interact with and target the Umu-like mutagenesis proteins to DNA. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS,BLDG 6,ROOM 1A13,BETHESDA,MD 20892. NR 37 TC 96 Z9 96 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1993 VL 90 IS 17 BP 8169 EP 8173 DI 10.1073/pnas.90.17.8169 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400055 PM 8367479 ER PT J AU BUKH, J PURCELL, RH MILLER, RH AF BUKH, J PURCELL, RH MILLER, RH TI AT LEAST 12 GENOTYPES OF HEPATITIS-C VIRUS PREDICTED BY SEQUENCE-ANALYSIS OF THE PUTATIVE E1-GENE OF ISOLATES COLLECTED WORLDWIDE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NON-A, NON-B HEPATITIS; GENETIC HETEROGENEITY; POLYMERASE CHAIN REACTION; DENDROGRAM; TAXONOMY ID NON-B HEPATITIS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; HUMAN CARRIERS; MUTATION-RATE; NON-A; GENOME; RNA; REGIONS; ORGANIZATION AB In a previous study we sequenced the 5' noncoding (NC) region of 44 isolates of hepatitis C virus (HCV) and identified heterogeneous domains that provided evidence for additional genetic groups of HCV not previously recognized. In this study we have determined the complete nucleotide sequence of the putative envelope 1 (E1) gene in 51 HCV isolates from around the world and found that they could be grouped into at least 12 distinct genotypes. The E1 gene sequence of 8 of these genotypes has not been reported previously. Although the genetic relatedness of HCV isolates determined by the previous analysis of the 5' NC region predicted the relationships observed in the E1 gene, analysis of the 5' NC sequence alone did not accurately predict all HCV genotypes. The nucleotide and amino acid sequence identities of the E1 gene among HCV isolates of the same genotype were in the range of 88.0-99.1% and 89.1-98.4%, respectively, whereas those of HCV isolates of different genotypes were in the range of 53.5-78.6% and 49.0-82.8%, respectively. The latter differences are similar to those found when comparing the envelope gene sequences of the various serotypes of the related flaviviruses as well as other RNA viruses. We found that some genotypes of HCV were widely distributed around the world, whereas others were identified only in discreet geographical regions. Four genotypes were identified exclusively in Aftica and comprised the majority of HCV isolates on that continent. The E1 gene was exactly 576 nucleotides in length in all 51 HCV isolates with no in-frame stop codons. Analysis of the predicted El protein identified several conserved domains that may be important for maintaining its biological function: (i) eight invariant cysteine residues, (ii) three potential N-linked glycosylation sites, (iii) a domain of nine amino adds (GHRMAWDMM), and (iv) an amino acid doublet (GV) near the putative cleavage site at the C terminus of the protein. In conclusion, the discovery of at least 12 genotypes of HCV has important implications for HCV diagnosis and vaccine development. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 30 TC 376 Z9 378 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 SEP 1 PY 1993 VL 90 IS 17 BP 8234 EP 8238 DI 10.1073/pnas.90.17.8234 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400068 PM 8396266 ER PT J AU BAKER, CS PERRY, A BANNISTER, JL WEINRICH, MT ABERNETHY, RB CALAMBOKIDIS, J LIEN, J LAMBERTSEN, RH RAMIREZ, JU VASQUEZ, O CLAPHAM, PJ ALLING, A OBRIEN, SJ PALUMBI, SR AF BAKER, CS PERRY, A BANNISTER, JL WEINRICH, MT ABERNETHY, RB CALAMBOKIDIS, J LIEN, J LAMBERTSEN, RH RAMIREZ, JU VASQUEZ, O CLAPHAM, PJ ALLING, A OBRIEN, SJ PALUMBI, SR TI ABUNDANT MITOCHONDRIAL-DNA VARIATION AND WORLDWIDE POPULATION-STRUCTURE IN HUMPBACK WHALES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EVOLUTION; PHYLOGENIES; NUCLEOTIDE; HAPLOTYPES; LIKELIHOOD; MIGRATION; SEQUENCE; TREES AB Hunting during the last 200 years reduced many populations of mysticete whales to near extinction. To evaluate potential genetic bottlenecks in these exploited populations, we examined mitochondrial DNA control region sequences from 90 individual humpback whales (Megaptera novaeangliae) representing six subpopulations in three ocean basins. Comparisons of relative nucleotide and nucleotype diversity reveal an abundance of genetic variation in all but one of the oceanic subpopulations. Phylogenetic reconstruction of nucleotypes and analysis of maternal gene flow show that current genetic variation is not due to postexploitation migration between oceans but is a relic of past population variability. Calibration of the rate of control region evolution across three families of whales suggests that existing humpback whale lineages are of ancient origin. Preservation of preexploitation variation in humpback whales may be attributed to their long life-span and overlapping generations and to an effective, though perhaps not timely, international prohibition against hunting. C1 UNIV HAWAII,DEPT ZOOL,HONOLULU,HI 96822. UNIV HAWAII,KEWALO MARINE LAB,HONOLULU,HI 96822. WESTERN AUSTRALIAN MUSEUM,PERTH,WA 6000,AUSTRALIA. CETACEAN RES UNIT,GLOUCESTER,MA 01930. UNIV PRETORIA,PRETORIA 0002,SOUTH AFRICA. CASCADIA RES COLLECT,OLYMPIA,WA 98501. MEM UNIV NEWFOUNDLAND,ST JOHNS A1C 5S7,NEWFOUNDLAND,CANADA. WOODS HOLE OCEANOG INST,WOODS HOLE,MA 02543. UNIV AUTONOM BAJA CALIF SUR,LA PAZ,BAJA CALIFORNIA,MEXICO. UNIV AUTONOMA SANTO DOMINGO,SANTO DOMINGO,DOMINICAN REP. CTR COASTAL STUDIES,PROVINCETOWN,MA 02657. OCEAN EXPEDIT INC,ORACLE,AZ 85624. NCI,FREDERICK,MD 21702. NR 48 TC 208 Z9 224 U1 6 U2 38 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 SEP 1 PY 1993 VL 90 IS 17 BP 8239 EP 8243 DI 10.1073/pnas.90.17.8239 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400069 PM 8367488 ER PT J AU LI, CY PEOPLES, RW LI, ZW WEIGHT, FF AF LI, CY PEOPLES, RW LI, ZW WEIGHT, FF TI ZN2+ POTENTIATES EXCITATORY ACTION OF ATP ON MAMMALIAN NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROTRANSMITTER; ION CHANNEL; DIVALENT CATION; PURINOCEPTOR ID ION CHANNELS; MAST-CELLS; RAT; RECEPTORS; RELEASE; ZN-2+; CALCIUM; NERVES; ZINC; NMDA AB Despite the increasing recognition that ATP is an important extracellular excitatory mediator in the nervous system, the regulation of ATP receptors is poorly understood. BeCause the extracellular Zn2+ concentration is regulated in a variety of biological tissues, we studied modulation of the ATP-gated cation channel by Zn2+ in mammalian neurons using the whole-cell patch-clamp technique. In almost-equal-to 73% of cells tested, the amplitude of ATP-activated membrane ion cuffent increased up to 5-fold in the presence of micromolar concentrations of Zn2+. The characteristics of this action suggest that Zn2+ increases the apparent affinity of the receptor for ATP. In addition, Zn2+ increased membrane depolarization and action potential firing eficited by ATP. These observations suggest that Zn2+ may play a physiological role in regulating the excitatory action of ATP on mammalian neurons. RP LI, CY (reprint author), NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 42 TC 103 Z9 110 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1993 VL 90 IS 17 BP 8264 EP 8267 DI 10.1073/pnas.90.17.8264 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LV644 UT WOS:A1993LV64400074 PM 7690146 ER PT J AU HERBERG, FW BELL, SM TAYLOR, SS AF HERBERG, FW BELL, SM TAYLOR, SS TI EXPRESSION OF THE CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE IN ESCHERICHIA-COLI - MULTIPLE ISOZYMES REFLECT DIFFERENT PHOSPHORYLATION STATES SO PROTEIN ENGINEERING LA English DT Article ID I REGULATORY SUBUNIT; AMINO-ACID-SEQUENCE; BOVINE CARDIAC-MUSCLE; SKELETAL-MUSCLE; MOLECULAR-CLONING; RABBIT SKELETAL; HEART; INHIBITOR; AUTOPHOSPHORYLATION; PURIFICATION AB The catalytic subunit of mouse cAMP-dependent protein kinase expressed in Escherichia coli was separated into three distinct species using Mono-S ion exchange chromatography. These isozymes corresponded to three isoelectric variants with pIs of 6.4 (30%), 7.2 (60%) and 8.2 (10%). The Stokes' radius of each form was 27.7, 27.1 and 26.3 angstrom respectively. Using electrospray mass spectroscopy the differences between the isozymes were shown to be due to phosphorylation, with each form differing by 80 mass units corresponding to a single phosphate. The fully phosphorylated recombinant enzyme contained four phosphates while the dominant isozyme contained only three. Since the enzyme is not phosphorylated when active site mutations are introduced into the C-subunit, these phosphates are incorporated in an autocatalytic mechanism and are not due to E.coli protein kinases. When the recombinant enzyme was compared with the mammalian porcine heart enzyme significant differences in post-translational modifications were observed. The mammalian enzyme could also be separated into two isozymes. However, in contrast to the recombinant enzyme, the mammalian isozymes displayed an identical mass of 40 840. This correlated with two different post-translational modifications: two phosphates and an N-terminal myristyl moiety. The importance of post-translational modifications, and in particular the phosphorylation state, for the expression of eukaryotic proteins in E.coli is discussed. C1 UNIV CALIF SAN DIEGO,DEPT CHEM,9500 GILMAN DR,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. NCI,FCRDC,PRI DYNCORP,BCDP,FREDERICK,MD 21702. RI Herberg, Friedrich/B-5572-2015 OI Herberg, Friedrich/0000-0001-7117-7653 FU NIGMS NIH HHS [GM19301] NR 52 TC 108 Z9 109 U1 0 U2 5 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 SEP PY 1993 VL 6 IS 7 BP 771 EP 777 DI 10.1093/protein/6.7.771 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LZ938 UT WOS:A1993LZ93800013 PM 8248101 ER PT J AU BOEGGEMAN, EE BALAJI, PV SETHI, N MASIBAY, AS QASBA, PK AF BOEGGEMAN, EE BALAJI, PV SETHI, N MASIBAY, AS QASBA, PK TI EXPRESSION OF DELETION CONSTRUCTS OF BOVINE BETA-1,4-GALACTOSYLTRANSFERASE IN ESCHERICHIA-COLI - IMPORTANCE OF CYS134 FOR ITS ACTIVITY SO PROTEIN ENGINEERING LA English DT Article DE AMINO-DELETED CONSTRUCTS; DISULFIDE BRIDGE MUTANTS; INCLUSION BODIES; RECOMBINANT BOVINE BETA-1,4-GALACTOSYLTRANSFERASE RENATURATION ID GLUTATHIONE-S-TRANSFERASE; N-ACETYLGLUCOSAMINE; ALPHA-LACTALBUMIN; GALACTOSYLTRANSFERASE; PURIFICATION; CLONING; CDNA; GLYCOSYLTRANSFERASES; BINDING; PROTEINS AB Bovine beta-1,4-galactosyltransferase (beta-1,4-GT; EC 2.4.1.90) belongs to the glycosyltransferase family and as such shares a general topology: an N-terminal cytoplasmic tail, a signal anchor followed by a stem region and a catalytic domain at the C-terminal end of the protein. cDNA constructs of the N-terminal deleted forms of beta-1,4-GT were prepared in pGEX-2T vector and expressed in E.coli as glutathione-S-transferase (GST) fusion proteins. Recombinant proteins accumulated within inclusion bodies as insoluble aggregates that were solubilized in 5 M guanidine HCI and required an 'oxido-shuffling' reagent for regeneration of the enzyme activity. The recombinant beta-1,4-GT, devoid of the GST domain, has 30-85% of the sp. act. of bovine milk beta-1,4-GT with apparent K(m)s for N-acetylglucosamine and UDP-galactose similar to those of milk enzyme. Deletion analyses show that both beta-1,4-GT and lactose synthetase activities remain intact even in the absence of the first 129 residues (pGT-d129). The activities are lost when either deletions extend up to residue 142 (pGT-d142) or Cys134 is mutated to Ser (pGT-d129C134S). These results suggest that the formation of a disulfide bond involving Cys134 holds the protein in a conformation that is required for enzymatic activity. C1 NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,PK 5 BLDG,ROOM 410,BETHESDA,MD 20892. NR 33 TC 46 Z9 46 U1 0 U2 3 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 SEP PY 1993 VL 6 IS 7 BP 779 EP 785 DI 10.1093/protein/6.7.779 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LZ938 UT WOS:A1993LZ93800014 PM 8248102 ER PT J AU WLODAWER, A PAVLOVSKY, A GUSTCHINA, A AF WLODAWER, A PAVLOVSKY, A GUSTCHINA, A TI HEMATOPOIETIC CYTOKINES - SIMILARITIES AND DIFFERENCES IN THE STRUCTURES, WITH IMPLICATIONS FOR RECEPTOR-BINDING SO PROTEIN SCIENCE LA English DT Article DE GROWTH FACTORS; INTERLEUKINS; RECEPTOR BINDING; SEQUENCE ALIGNMENT; STRUCTURE ALIGNMENT ID COLONY-STIMULATING FACTOR; HUMAN RECOMBINANT INTERLEUKIN-4; HUMAN GROWTH-HORMONE; AMINO-ACID-RESIDUES; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; MOUSE INTERLEUKIN-2; BIOLOGICAL-ACTIVITY; INTERFERON-GAMMA; X-RAY AB Crystal and NMR structures of helical cytokines-interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-2 (IL-2)-have been compared. Root mean square deviations in the C(alpha) coordinates for the conserved regions of the helices were 1-2 angstrom between different cytokines, about twice the differences observed for independently determined crystal and solution structures of IL-4. Considerable similarity in amino acid sequence in the areas expected to interact with the receptors was detected, and the available mutagenesis data for these cytokines were correlated with structure conservation. Models of cytokine-receptor interactions were postulated for IL-4 based on its structure as well as on the published structure of human growth hormone interacting with its receptors (de Vos, A.M., Ultsch, M., & Kossiakoff, A.A., 1992, Science 255, 306-312). Patches of positively charged residues on the surfaces of helices C and D of IL-4 may be responsible for the interactions with the negatively charged residues found in the complementary parts of the IL-4 receptors. RP WLODAWER, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 45 TC 43 Z9 43 U1 0 U2 1 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 SEP PY 1993 VL 2 IS 9 BP 1373 EP 1382 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LU650 UT WOS:A1993LU65000002 PM 8401223 ER PT J AU GIAMBRA, LM ARENBERG, D AF GIAMBRA, LM ARENBERG, D TI ADULT AGE-DIFFERENCES IN FORGETTING SENTENCES SO PSYCHOLOGY AND AGING LA English DT Article ID CONTINUOUS RECOGNITION MEMORY; VERBAL LISTS; INDEPENDENCE; RETENTION; DYNAMICS; STORAGE; CURVES; RATES AB Age comparisons of performance-based measures of forgetting were carried out. In Exp. 1, 18- to 21-year-olds and 55- to 64-year-olds (n = 24) forgot at an equal rate when compared at 30 s and at 3,6, and 24 hr after acquisition. In Exp. 2, 17- to 21-year-olds and 65- to 74-year-olds (n = 24) were compared at the same 4 retention intervals. Initial learning was equated for the 2 groups. There was evidence for an age difference in forgetting rate in cued recall when a minimal learning level was required. In Exp. 3, 440 men and women 17 to 74 years old were assigned to a retention interval from 10 min to 7 hr. Age was related to 4 performance-based measures of forgetting rate. Although the age differences were small, they imply 2 decremental processes: 1 before 10 min, possibly a result of incomplete consolidation, and a later 1 that is continuously and cumulatively operative thereafter. Evidence relating initial level to forgetting rate is presented. RP GIAMBRA, LM (reprint author), NATL INST AGING,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 27 TC 30 Z9 31 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 1993 VL 8 IS 3 BP 451 EP 462 DI 10.1037//0882-7974.8.3.451 PG 12 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA LY973 UT WOS:A1993LY97300017 PM 8216966 ER PT J AU SUDAKOV, SK GOLDBERG, SR BORISOVA, EV SURKOVA, LA TURINA, IV RUSAKOV, DJ ELMER, GI AF SUDAKOV, SK GOLDBERG, SR BORISOVA, EV SURKOVA, LA TURINA, IV RUSAKOV, DJ ELMER, GI TI DIFFERENCES IN MORPHINE REINFORCEMENT PROPERTY IN 2 INBRED RAT STRAINS - ASSOCIATIONS WITH CORTICAL RECEPTORS, BEHAVIORAL ACTIVITY, ANALGESIA AND THE CATALEPTIC EFFECTS OF MORPHINE SO PSYCHOPHARMACOLOGY LA English DT Article DE MORPHINE; BEHAVIORAL ACTIVITY; ANALGESIA; RAT; SELF-ADMINISTRATION; GENETICS ID SENSITIVITY; ABUSE AB The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in mu and alpha2 receptor concentrations (F344/N > WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto > F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions. C1 NIDA, ADDICT RES CTR, PRECLIN PHARMACOL LAB, BEHAV PHARMACOL & GENET SECT, BALTIMORE, MD 21224 USA. RP SUDAKOV, SK (reprint author), ALL UNION RES CTR ADDICT, INST MEDICOBIOL PROBLEMS ADDICT, EXPTL THERAPY DRUG ABUSE LAB, MOSCOW 121002, RUSSIA. NR 20 TC 30 Z9 30 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1993 VL 112 IS 2-3 BP 183 EP 188 DI 10.1007/BF02244908 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LW907 UT WOS:A1993LW90700003 PM 7871017 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI SENTINEL FOR HEALTH - A HISTORY OF THE CENTERS-FOR-DISEASE-CONTROL - ETHERIDGE,EW SO PUBLIC HISTORIAN LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CALIF PRESS PI BERKELEY PA JOURNALS DEPT 2120 BERKELEY WAY, BERKELEY, CA 94720 SN 0272-3433 J9 PUBL HISTORIAN JI Public Hist. PD FAL PY 1993 VL 15 IS 4 BP 123 EP 124 PG 2 WC History SC History GA MH910 UT WOS:A1993MH91000035 ER PT J AU ACKERMAN, MJ AF ACKERMAN, MJ TI INFORAD - INFORMATICS IN RADIOLOGY - HIGH-PERFORMANCE COMPUTING AND COMMUNICATIONS SO RADIOGRAPHICS LA English DT Editorial Material RP ACKERMAN, MJ (reprint author), NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1993 VL 13 IS 5 BP 1129 EP 1130 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LX216 UT WOS:A1993LX21600015 PM 8210594 ER PT J AU DOPPMAN, JL AF DOPPMAN, JL TI THE DILEMMA OF BILATERAL ADRENOCORTICAL NODULARITY IN CONNS AND CUSHINGS SYNDROMES SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID MACRONODULAR ADRENAL-HYPERPLASIA; PRIMARY ALDOSTERONISM; UNILATERAL ALDOSTERONOMA; CLINICAL-SIGNIFICANCE; DISEASE; CT; DIAGNOSIS; LOCALIZATION; HYPERALDOSTERONISM; LESIONS C1 HENRY M JACKSON FDN,ROCKVILLE,MD. RP DOPPMAN, JL (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM C660,BETHESDA,MD 20892, USA. NR 23 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1993 VL 31 IS 5 BP 1039 EP 1050 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LV511 UT WOS:A1993LV51100006 PM 8362054 ER PT J AU MILLER, DL AF MILLER, DL TI ENDOCRINE ANGIOGRAPHY AND VENOUS SAMPLING SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; SELECTIVE INTRAARTERIAL INJECTION; CORTICOTROPIN-RELEASING HORMONE; ISLET CELL TUMORS; PARATHYROID ADENOMAS; INTRAOPERATIVE ULTRASONOGRAPHY; PRIMARY HYPERPARATHYROIDISM; PREOPERATIVE LOCALIZATION; NEUROLOGIC COMPLICATIONS; DIFFERENTIAL-DIAGNOSIS C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT RADIOL,WASHINGTON,DC 20057. NR 77 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1993 VL 31 IS 5 BP 1051 EP 1067 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LV511 UT WOS:A1993LV51100007 PM 8362055 ER PT J AU POSSE, S CUENOD, CA LEBIHAN, D AF POSSE, S CUENOD, CA LEBIHAN, D TI HUMAN BRAIN - PROTON DIFFUSION MR SPECTROSCOPY SO RADIOLOGY LA English DT Article; Proceedings Paper CT 79TH SCIENTIFIC ASSEMBLY AND 1992 ANNUAL MEETING OF THE RADIOLOGICAL SOC OF NORTH AMERICA CY NOV 28-DEC 03, 1992 CL CHICAGO, IL SP RADIOL SOC N AMER DE BRAIN, PERFUSION; MAGNETIC RESONANCE (MR), DIFFUSION STUDY; MAGNETIC RESONANCE (MR), SPECTROSCOPY; MAGNETIC RESONANCE (MR), TISSUE CHARACTERIZATION ID LOCALIZED SPECTROSCOPY; STIMULATED ECHOES; NMR-SPECTROSCOPY; MOTION; INVIVO; WATER; METABOLITES; SEPARATION; RELAXATION; PERFUSION AB Diffusion of brain metabolites was measured in 10 healthy volunteers by using localized proton diffusion magnetic resonance (MR) spectroscopy. Measurements were conducted with a clinical MR imager by using a stimulated-echo pulse sequence (3,000/60 [repetition time msec/echo time msec], 200-msec mixing time) with additional outside-volume suppression. Motion artifacts due to macroscopic brain movements were compensated by means of peripheral cardiac gating and separate collection of individual spectroscopic acquisitions into a two-dimensional data matrix. Phase errors due to macroscopic motion were subsequently corrected in individual data traces prior to spectral averaging. Mean (+/- 1 standard deviation) apparent diffusion coefficients of choline-containing compounds ([0.13 +/- 0.03] x 10(-3) mm2/sec), creatine and phosphocreatine ([0.15 +/- 0.03] x 10(-3) mm2/sec), and N-acetyl aspartate ([0.18 +/- 0.02] x 10(-3) mm2/sec) were substantially smaller than that of water and were consistent with recently published data obtained in anesthetized and paralyzed animals. Adequate diffusion sensitivity for metabolites in the human brain can be obtained with clinical whole-body imagers despite macroscopic head and brain movements. C1 NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RP POSSE, S (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 34 TC 72 Z9 72 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1993 VL 188 IS 3 BP 719 EP 725 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LT863 UT WOS:A1993LT86300026 PM 8351339 ER PT J AU PAUL, WE AF PAUL, WE TI INFECTIOUS-DISEASES AND THE IMMUNE-SYSTEM SO SCIENTIFIC AMERICAN LA English DT Article ID CELL RP PAUL, WE (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 1 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 1993 VL 269 IS 3 BP 90 EP 97 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LR869 UT WOS:A1993LR86900012 PM 8211095 ER PT J AU BALE, SJ COMPTON, JG DIGIOVANNA, JJ AF BALE, SJ COMPTON, JG DIGIOVANNA, JJ TI EPIDERMOLYTIC HYPERKERATOSIS SO SEMINARS IN DERMATOLOGY LA English DT Article RP BALE, SJ (reprint author), NIAMS,SBB,GENET STUDIES SECT,BLDG 6,RM 429,BETHESDA,MD 20892, USA. NR 0 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-145X J9 SEMIN DERMATOL JI Semin. Dermatol. PD SEP PY 1993 VL 12 IS 3 BP 202 EP 209 PG 8 WC Dermatology SC Dermatology GA LX054 UT WOS:A1993LX05400006 PM 7692917 ER PT J AU KUSEK, JW AGODOA, LY JONES, CA AF KUSEK, JW AGODOA, LY JONES, CA TI DO WE NEED ANOTHER COOPERATIVE DIALYSIS STUDY - COMMENT SO SEMINARS IN DIALYSIS LA English DT Letter RP KUSEK, JW (reprint author), NIDDKD,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP-OCT PY 1993 VL 6 IS 5 BP 325 EP 326 DI 10.1111/j.1525-139X.1993.tb00507.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA LY139 UT WOS:A1993LY13900014 ER PT J AU STRIKER, LJ AF STRIKER, LJ TI MODERN RENAL BIOPSY INTERPRETATION - CAN WE PREDICT GLOMERULOSCLEROSIS SO SEMINARS IN NEPHROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA LEVELS; GROWTH FACTOR-I; EXTRACELLULAR-MATRIX; GLOMERULAR HYPERTROPHY; DIABETIC NEPHROPATHY; COLLAGEN-SYNTHESIS; MESANGIAL CELLS; TRANSGENIC MICE; DISEASE C1 NIH,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. NR 49 TC 18 Z9 18 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD SEP PY 1993 VL 13 IS 5 BP 508 EP 515 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA LX616 UT WOS:A1993LX61600012 PM 8210814 ER PT J AU BAUER, HM HILDESHEIM, A SCHIFFMAN, MH GLASS, AG RUSH, BB SCOTT, DR CADELL, DM KURMAN, RJ MANOS, MM AF BAUER, HM HILDESHEIM, A SCHIFFMAN, MH GLASS, AG RUSH, BB SCOTT, DR CADELL, DM KURMAN, RJ MANOS, MM TI DETERMINANTS OF GENITAL HUMAN PAPILLOMAVIRUS INFECTION IN LOW-RISK WOMEN IN PORTLAND, OREGON SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID CERVICAL-CANCER; PREVALENCE AB Objectives: To confirm the risk factors for genital human papillomavirus (HPV) infection. Goal of this study: To investigate risk factors for HPV detection independent of the correlated risk factors for cervical neoplasia in a low-risk population. Study Design: HPV DNA was assessed among 483 cytologically normal women with no known history of cervical neoplasia. A cervicovaginal lavage was collected for HPV detection and typing using a PCR-based DNA amplification system. Information on risk factors of subjects was obtained through a questionnaire. Results: HPV DNA was found in 17.7% of study women. On univariate analysis, factors associated with increasing HPV prevalence included younger age, fewer years of education, lower income, higher lifetime number of sex partners, lower age at first intercourse, nulliparity, oral contraceptive use, and current smoking. After statistical adjustment, we found younger age and higher number of sex partners were strongly and independently associated with higher HPV prevalence. We also observed increased HPV prevalence among women with lower levels of education and lower incomes. Conclusion: These findings and corroborative data from the companion reports in this issue of the journal support the sexual route of transmission of the virus. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. CETUS CORP,DEPT INFECT DIS,EMERYVILLE,CA 94608. KAISER PERMANENTE,PORTLAND,OR. WESTAT CORP,ROCKVILLE,MD. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. ROCHE MOLEC SYST,DEPT INFECT DIS,ALAMEDA,CA. NR 16 TC 189 Z9 191 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP-OCT PY 1993 VL 20 IS 5 BP 274 EP 278 DI 10.1097/00007435-199309000-00007 PG 5 WC Infectious Diseases SC Infectious Diseases GA LY244 UT WOS:A1993LY24400007 PM 8235925 ER PT J AU HILDESHEIM, A GRAVITT, P SCHIFFMAN, MH KURMAN, RJ BARNES, W JONES, S TCHABO, JG BRINTON, LA COPELAND, C EPP, J MANOS, MM AF HILDESHEIM, A GRAVITT, P SCHIFFMAN, MH KURMAN, RJ BARNES, W JONES, S TCHABO, JG BRINTON, LA COPELAND, C EPP, J MANOS, MM TI DETERMINANTS OF GENITAL HUMAN PAPILLOMAVIRUS INFECTION IN LOW-INCOME WOMEN IN WASHINGTON, DC SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID CERVICAL-CANCER; RISK-FACTORS; YOUNG-WOMEN; PREVALENCE; ASSOCIATION AB Objectives: To confirm the risk factors for genital human papillomavirus (HPV) infection. Goal of this Study: To investigate risk factors for HPV detection independent of the correlated risk factors for cervical neoplasia, in a high-risk population. Study Design: We investigated 404 cytologically normal women attending medical assistance clinics in the Washington, D.C. area. Risk factor information was obtained and a cervicovaginal lavage was collected and used for HPV detection and typing by a PCR-based technique. Results. The point prevalence of HPV was 33.7%. This contrasts with the 17.7% and 44.3% observed in the companion reports published in this issue of the journal.1,2 HPV prevalence decreased with age and increased with greater numbers of sexual partners. Moreover, more recent sexual behavior was a better predictor of current HPV detection than lifetime number of sexual partners. Numbers of pregnancies and current pregnancy were positively associated with HPV prevalence and there was an indication that current oral contraceptive users had a higher prevalence of HPV compared to never users. Smoking was not associated with increased HPV prevalence. Conclusion: Findings support the sexual route of transmission of HPV and confirm the association of HPV detection with age, suggesting the host's ability to clear infection or the virus' ability to become latent. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. ROCHE MOLEC SYST, ALAMEDA, CA USA. GEORGETOWN UNIV, MED CTR, WASHINGTON, DC 20007 USA. JOHNS HOPKINS UNIV HOSP, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV HOSP, DEPT PATHOL, BALTIMORE, MD 21205 USA. DC GEN HOSP, WASHINGTON, DC USA. ARLINGTON HOSP, ARLINGTON, VA USA. RP HILDESHEIM, A (reprint author), CETUS CORP, NCI, DEPT INFECT DIS, ENVIRONM EPIDEMIOL BRANCH, EMERYVILLE, CA 94608 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 25 TC 135 Z9 136 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP-OCT PY 1993 VL 20 IS 5 BP 279 EP 285 DI 10.1097/00007435-199309000-00008 PG 7 WC Infectious Diseases SC Infectious Diseases GA LY244 UT WOS:A1993LY24400008 PM 8235926 ER PT J AU WHEELER, CM PARMENTER, CA HUNT, WC BECKER, TM GREER, CE HILDESHEIM, A MANOS, MM AF WHEELER, CM PARMENTER, CA HUNT, WC BECKER, TM GREER, CE HILDESHEIM, A MANOS, MM TI DETERMINANTS OF GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG CYTOLOGICALLY NORMAL WOMEN ATTENDING THE UNIVERSITY-OF-NEW-MEXICO STUDENT HEALTH-CENTER SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID RISK-FACTORS; CERVICAL-CANCER; PREVALENCE; ASSOCIATION AB Objectives: To confirm the risk factors for genital human papillomavirus (HPV) infection. Goal of this study:' To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. Study Design: Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. Results: A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. Conclusion: These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus. C1 UNIV NEW MEXICO,DEPT MED,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,DEPT FAMILY & COMMUNITY MED,ALBUQUERQUE,NM 87131. NEW MEXICO TUMOR REGISTRY,ALBUQUERQUE,NM. CETUS CORP,DEPT INFECT DIS,EMERYVILLE,CA 94608. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP WHEELER, CM (reprint author), UNIV NEW MEXICO,DEPT CELL BIOL,900 CAMINO SALUD NE,ALBUQUERQUE,NM 87131, USA. NR 16 TC 140 Z9 142 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP-OCT PY 1993 VL 20 IS 5 BP 286 EP 289 DI 10.1097/00007435-199309000-00009 PG 4 WC Infectious Diseases SC Infectious Diseases GA LY244 UT WOS:A1993LY24400009 PM 8235927 ER PT J AU ALLEN, RP MCCANN, UD RICAURTE, GA AF ALLEN, RP MCCANN, UD RICAURTE, GA TI PERSISTENT EFFECTS OF (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) ON HUMAN SLEEP SO SLEEP LA English DT Article DE MDMA; SEROTONIN; NEUROTOXICITY; AMPHETAMINES; SLEEP ID CENTRAL SEROTONERGIC NEURONS; RAT-BRAIN; MONOAMINERGIC SYSTEMS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; TERMINALS; MDA AB (+/-)3,4-methylenedioxymethamphetamine (MDMA) is a recreational drug of abuse which damages serotonin neurons in animals. It is not known whether MDMA is also neurotoxic in humans, and if so, whether there are functional consequences. Given the putative role of serotonin in sleep, it was hypothesized that one manifestation of serotonin neurotoxicity in humans might be disturbances of sleep. To determine whether MDMA use has effects on sleep, all-night polysomnograms of 23 MDMA users were compared to those of 22 age- and sex-matched controls. On average, MDMA users had 19 minutes less total sleep and 23.2 minutes less non-REM (NREM) sleep than controls. These statistically significant differences in NREM sleep were due primarily to an average of 37 minutes less stage 2 sleep, with no significant differences noted in stages 1, 3 or 4. Although it is not known whether the alterations in sleep observed in MDMA users are due to serotonin neurotoxicity, the present findings suggest that MDMA use can lead to persistent changes in CNS structures involved in human sleep generation. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,FRANCIS SCOTT KEY MED CTR,DEPT NEUROL,BALTIMORE,MD 21205. FU NIDA NIH HHS [NIDA DA05707] NR 32 TC 82 Z9 82 U1 0 U2 4 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 SEP PY 1993 VL 16 IS 6 BP 560 EP 564 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LZ543 UT WOS:A1993LZ54300009 PM 7901886 ER PT J AU HOWARD, G SHARRETT, AR HEISS, G EVANS, GW CHAMBLESS, LE RILEY, WA BURKE, GL AF HOWARD, G SHARRETT, AR HEISS, G EVANS, GW CHAMBLESS, LE RILEY, WA BURKE, GL TI CAROTID-ARTERY INTIMAL-MEDIAL THICKNESS DISTRIBUTION IN GENERAL POPULATIONS AS EVALUATED BY B-MODE ULTRASOUND SO STROKE LA English DT Article DE ATHEROSCLEROSIS; CAROTID ARTERIES; ULTRASONICS ID ASYMPTOMATIC PATIENTS; HEART-DISEASE; RISK-FACTORS; ATHEROSCLEROSIS; BRUITS; ULTRASONOGRAPHY AB Background and Purpose: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article provides a description or the distribution of carotid atherosclerosis in the general population. Methods: Intimal-medial arterial wall thickness was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The distribution was described by race-sex strata, in which 759 to 4952 individuals were imaged depending on strata and location in the carotid system. Results: Median wall thickness ranged between 0.5 and 1 mm at all ages; fewer than 5% of ARIC participants had values exceeding 2 mm. Individuals tended to have a larger wall thickness in the carotid bifurcation than in the common carotid artery. Internal carotid artery values were more variable, with higher proportions of both large and small wall thicknesses than in the common carotid. The proportion of individuals with a large wall thickness was greatest at the bifurcation and smallest at the common carotid artery. Men had uniformly larger wall thickness than women. Cross-sectional analysis suggests that age-related increases in wall thickness average approximately 0.015 mm/y in women and 0.018 mm/y in men in the carotid bifurcation, 0.010 mm/y for women and 0.014 mm/y for men in the internal carotid artery, and 0.010 mm/y in both sexes in the common carotid artery. Conclusions: Estimates provided for wall thickness percentiles can serve as ''nomograms'' by age, race, and sex. C1 WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT NEUROL, WINSTON SALEM, NC 27157 USA. NHLBI, BETHESDA, MD 20892 USA. UNIV N CAROLINA, SCH PUBL HLTH, DEPT EPIDEMIOL, CHAPEL HILL, NC 27514 USA. UNIV N CAROLINA, SCH PUBL HLTH, DEPT BIOSTAT, CHAPEL HILL, NC 27514 USA. RP HOWARD, G (reprint author), WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, MED CTR BLVD, WINSTON SALEM, NC 27157 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 26 TC 470 Z9 484 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1993 VL 24 IS 9 BP 1297 EP 1304 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA LW042 UT WOS:A1993LW04200004 PM 8362421 ER PT J AU UNTERWALD, EM COX, BM KREEK, MJ COTE, TE IZENWASSER, S AF UNTERWALD, EM COX, BM KREEK, MJ COTE, TE IZENWASSER, S TI CHRONIC REPEATED COCAINE ADMINISTRATION ALTERS BASAL AND OPIOID-REGULATED ADENYLYL-CYCLASE ACTIVITY SO SYNAPSE LA English DT Article DE MU-OPIOID; DELTA-OPIOID; DAMGO; DPDPE; DOPAMINE; RAT BRAIN; CAUDATE PUTAMEN; NUCLEUS ACCUMBENS ID RAT NUCLEUS-ACCUMBENS; RECEPTOR FUNCTION; OPIATE RECEPTOR; DOPAMINE UPTAKE; H-3 DOPAMINE; BRAIN; INHIBITION; REINFORCEMENT; INTERMITTENT; STIMULATION AB Repeated daily cocaine injections have been shown to alter mu-opioid receptor densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et al., 1991, 1992). Adenylyl cyclase activity was measured in rat rostral caudate putamen and nucleus accumbens following repeated cocaine administration to determine the functional consequences of cocaine-induced opioid receptor changes. Male Fischer rats were injected daily for 14 days with saline or cocaine HCI (30 or 45 mg/kg/day, i.p.) in three equal doses at 1-hr intervals. Basal adenylyl cyclase activity and the effects of the selective mu- and delta-opioid agonists [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) and [D-penicillamine2,D-Penicillamine5]enkephalin (DPDPE), respectively, on adenylyl cyclase activity were examined 30 min after the last injection using a cAMP radioligand binding assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and 34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of cocaine, respectively, as compared to those receiving saline injections. Basal adenylyl cyclase activity was unchanged in the nucleus accumbens following cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and 30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus accumbens of saline-injected animals. Administration of cocaine attenuated the ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase activity. These results suggest that chronic, repeated cocaine administration results in a selective impairment of delta-opioid receptor-mediated effector function in the caudate putamen and nucleus accumbens. (C) 1993 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP UNTERWALD, EM (reprint author), ROCKEFELLER UNIV,NEW YORK,NY 10021, USA. RI Izenwasser, Sari/G-9193-2012 FU NIDA NIH HHS [ADA MHA-NIDA DA-00049, NIDA DA 04953, NIDA DA-P50-05130] NR 34 TC 62 Z9 63 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1993 VL 15 IS 1 BP 33 EP 38 DI 10.1002/syn.890150104 PG 6 WC Neurosciences SC Neurosciences & Neurology GA LU841 UT WOS:A1993LU84100003 PM 8310423 ER PT J AU KITAYAMA, S WANG, JB UHL, GR AF KITAYAMA, S WANG, JB UHL, GR TI DOPAMINE TRANSPORTER MUTANTS SELECTIVELY ENHANCE MPP+ TRANSPORT SO SYNAPSE LA English DT Article DE DOPAMINE TRANSPORTER; MUTAGENESIS; MPP+; PARKINSONS DISEASE; NEUROTOXIN ID PARKINSONS-DISEASE; COCAINE; CLONING; BINDING; NEUROTRANSMITTER; NORADRENALINE; RECEPTORS; CELLS; BRAIN; CDNA AB MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that provides the best available experimental model of Parkinson's disease, is selectively concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also serves as a primary recognition site for cocaine. To help define selective molecular mechanisms by which MPP+ uptake occurs, we have tested dopamine transporters mutated in several residues for their abilities to accumulate dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th hydrophobic putative transmembrane domains increase MPP+ uptake velocity and affinity (1/K(D)), respectively. These mutations exert much more modest effects on dopamine uptake and have little impact on cocaine analog binding. These findings provide the first example of mutations that enhance transport and identify specific DAT amino acids selectively involved in neurotoxin uptake. They may also have implications for the feasibility of developing drugs that could specifically block accumulation of Parkinsonism-inducing neurotoxins. (C) 1993 Wiley-Liss, Inc.* C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BOX 5180,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 20 TC 80 Z9 83 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1993 VL 15 IS 1 BP 58 EP 62 DI 10.1002/syn.890150107 PG 5 WC Neurosciences SC Neurosciences & Neurology GA LU841 UT WOS:A1993LU84100006 PM 8310426 ER PT J AU CONLAN, MG FOLSOM, AR FINCH, A DAVIS, CE SORLIE, P MARCUCCI, G WU, KK AF CONLAN, MG FOLSOM, AR FINCH, A DAVIS, CE SORLIE, P MARCUCCI, G WU, KK TI ASSOCIATIONS OF FACTOR-VIII AND VON-WILLEBRAND-FACTOR WITH AGE, RACE, SEX, AND RISK-FACTORS FOR ATHEROSCLEROSIS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID IMPROVED LIPOLYTIC EFFICIENCY; ISCHEMIC HEART-DISEASE; HEMOSTATIC VARIABLES; DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; ENZYMATIC DETERMINATION; CARDIOVASCULAR-DISEASE; INDUSTRIAL-POPULATION; PLASMA-FIBRINOGEN; PLATELET-FUNCTION AB Several coagulation proteins have been implicated as possible risk factors for the development of atherosclerotic diseases, among which are factor VIII and von Willebrand factor. As part of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study designed to assess risk factors for the development of atherosclerotic diseases, baseline measurements of factor VIII and von Willebrand factor (vWF) were performed to determine their relationship to the development of atherosclerosis. We herein report the associations of factor VIII and vWF with constitutional, lifestyle, and biochemical factors. Factor VIII and vWF were strongly correlated with each other (r = 0.73), and, therefore, had similar associations with risk factors. Mean levels of both factors were higher in women than in men, in blacks than in whites, and increased with age. In univariate analysis, both were positively associated with diabetes, body mass index, waist-to-hip ratio, serum insulin, and plasma triglycerides. Both were negatively associated with alcohol intake, educational level, physical activity (with some exceptions), and HDL-cholesterol. No correlations were observed between factor VIII or vWF and plasma LDL-cholesterol or lipoprotein(a). Although factor VIII was negatively associated with smoking in both sexes, vWF was not associated with smoking status. Most of these associations were confirmed in multivariate analysis. The strongest associations observed were of factor VIII and vWF with race and diabetes. In multivariate analysis, blacks had factor VIII and vWF levels 15 to 18 percentage points higher than whites, and diabetics had factor VIII and vWF levels 11 to 18 percentage points higher than non-diabetics. These associations must be taken into account when analyzing the possible role of factor VIII and vWF in the development of atherosclerotic diseases. C1 UNIV MINNESOTA,SCH PUBL HLTH,DEPT EPIDEMIOL,SUITE 300,1300 S 2ND ST,MINNEAPOLIS,MN 55455. UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX 77025. UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55015, N01-HC-55018] NR 53 TC 313 Z9 319 U1 0 U2 6 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP 1 PY 1993 VL 70 IS 3 BP 380 EP 385 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LV870 UT WOS:A1993LV87000001 PM 8259533 ER PT J AU LAFRANCHI, S DUSSAULT, JH FISHER, DA FOLEY, TP MITCHELL, ML SEASHORE, MR CHO, S DESPOSITO, F HALL, JG SHERMAN, J WILSON, MG DELACRUZ, F HANSON, JW LINFU, J MENNUTI, M OAKLEY, G MITCHELL, ML SPENCER, CA RALLISON, ML BECKER, DV GAITAN, E VANMIDDLESWORTH, L AF LAFRANCHI, S DUSSAULT, JH FISHER, DA FOLEY, TP MITCHELL, ML SEASHORE, MR CHO, S DESPOSITO, F HALL, JG SHERMAN, J WILSON, MG DELACRUZ, F HANSON, JW LINFU, J MENNUTI, M OAKLEY, G MITCHELL, ML SPENCER, CA RALLISON, ML BECKER, DV GAITAN, E VANMIDDLESWORTH, L TI NEWBORN SCREENING FOR CONGENITAL HYPOTHYROIDISM - RECOMMENDED GUIDELINES SO THYROID LA English DT Review ID NEONATAL-HYPOTHYROIDISM; THYROXINE; PROGRAM; THYROTROPIN C1 NIH,BETHESDA,MD 20892. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. RP LAFRANCHI, S (reprint author), OREGON HLTH SCI UNIV,DEPT PEDIAT,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1993 VL 3 IS 3 BP 257 EP 263 DI 10.1089/thy.1993.3.257 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA711 UT WOS:A1993MA71100015 ER PT J AU ANDERSON, YB COULBERSON, SL PHELPS, J AF ANDERSON, YB COULBERSON, SL PHELPS, J TI OVERVIEW OF THE EPA NIEHS/ATSDR WORKSHOP - EQUITY IN ENVIRONMENTAL-HEALTH - RESEARCH ISSUES AND NEEDS SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE ENVIRONMENTAL EQUITY; ENVIRONMENTAL JUSTICE; WORKSHOP OVERVIEW C1 AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. NIEHS,RES TRIANGLE PK,NC 27709. RP ANDERSON, YB (reprint author), US EPA,HLTH EFFECTS RES LAB,MD-5,RES TRIANGLE PK,NC 27711, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP-OCT PY 1993 VL 9 IS 5 BP 679 EP 683 PG 5 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MW434 UT WOS:A1993MW43400002 PM 8184440 ER PT J AU SEXTON, K OLDEN, K JOHNSON, BL AF SEXTON, K OLDEN, K JOHNSON, BL TI ENVIRONMENTAL JUSTICE - THE CENTRAL ROLE OF RESEARCH IN ESTABLISHING A CREDIBLE SCIENTIFIC FOUNDATION FOR INFORMED DECISION-MAKING SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE ENVIRONMENTAL EQUITY; ENVIRONMENTAL HEALTH RESEARCH; ENVIRONMENTAL HEALTH RISKS; ENVIRONMENTAL JUSTICE ID CANCER INCIDENCE; RISK ASSESSMENT; BLACKS AB Although much of the evidence is anecdotal and circumstantial, there are mounting concerns that environmental health risks are borne disproportionately by members of the population who are poor and nonwhite. We examine the central role of environmental health research in defining the dimensions of the problem, understanding its causes, and identifying solutions. Environmental health sciences, including epidemiology, exposure analysis, pharmacokinetics, toxicology, and surveillance monitoring, must be employed to determine the extent to which society has achieved ''equity'' and ''justice'' in safeguarding the health and safety of its citizens. By improving our ability to identify, evaluate, prevent, and/or reduce risks for all members of society, environmental health research can contribute directly to fair and equitable protection for everyone, regardless of age, ethnicity, gender, race, or socioeconomic status. C1 NIEHS,RES TRIANGLE PK,NC 27709. AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. RP SEXTON, K (reprint author), US EPA,OFF HLTH RES,WASHINGTON,DC 20250, USA. NR 97 TC 63 Z9 63 U1 1 U2 8 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP-OCT PY 1993 VL 9 IS 5 BP 685 EP 727 PG 43 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MW434 UT WOS:A1993MW43400003 PM 8184441 ER PT J AU RIOS, R POJE, GV DETELS, R AF RIOS, R POJE, GV DETELS, R TI SUSCEPTIBILITY TO ENVIRONMENTAL-POLLUTANTS AMONG MINORITIES SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE ENVIRONMENTAL EXPOSURES; ENVIRONMENTAL POLLUTANTS; MINORITY GROUPS; OCCUPATIONAL RISK FACTORS; SUSCEPTIBILITY ID UNITED-STATES; MORTALITY; PREVALENCE; PATTERNS; DISEASE; WORKERS; TRENDS AB Susceptibility to environmental pollutants involves both biological and nonbiological factors. Individuals belonging to minority groups are much more likely to be subject to a number of these factors. This paper examines biological susceptibility of minorities to environmental pollutants and provides specific examples of susceptibility resulting from: genetic makeup; occupation; other factors such as compromised health status, exposure to mixtures of pollutants, substance abuse, and unemployment, and social inequality of access to health care, education, and communication skills. Recommendations are made for specific actions and for additional studies. C1 NIH, BETHESDA, MD 20892 USA. RP RIOS, R (reprint author), UNIV CALIF LOS ANGELES, SCH PUBL HLTH, DEPT EPIDEMIOL, 10833 LE CONTE AVE, LOS ANGELES, CA 90024 USA. NR 80 TC 24 Z9 24 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP-OCT PY 1993 VL 9 IS 5 BP 797 EP 820 PG 24 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MW434 UT WOS:A1993MW43400006 PM 8184444 ER PT J AU MOSES, M JOHNSON, ES ANGER, WK BURSE, VW HORSTMAN, SW JACKSON, RJ LEWIS, RG MADDY, KT MCCONNELL, R MEGGS, WJ ZAHM, SH AF MOSES, M JOHNSON, ES ANGER, WK BURSE, VW HORSTMAN, SW JACKSON, RJ LEWIS, RG MADDY, KT MCCONNELL, R MEGGS, WJ ZAHM, SH TI ENVIRONMENTAL EQUITY AND PESTICIDE EXPOSURE SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Review DE AGRICULTURE; CANCER; NEUROLOGICAL; PESTICIDES; RACE; REPRODUCTIVE ID NON-HODGKINS LYMPHOMA; POLYCHLORINATED BIPHENYL RESIDUES; NEURO-BEHAVIORAL EVALUATION; CENTRAL-NERVOUS-SYSTEM; SOFT-TISSUE SARCOMA; AGRICULTURAL-WORKERS; PARKINSONS-DISEASE; METHYL-BROMIDE; TESTICULAR CANCER; BIRTH-DEFECTS AB Although people of color and low-income groups bear a disproportionate share of the health risks from exposure to pesticides, research attention has been meager, and data on acute and chronic health effects related to their toxic exposures are generally lacking. Increased resources are needed both to study this issue and to mitigate problems already identified. People of color should be a major research focus, with priority on long-term effects, particularly cancer, neurodevelopmental and neurobehavioral effects, long-term neurological dysfunction, and reproductive outcome. Suitable populations at high risk that have not been studied include noncertified pesticide applicators and seasonal and migrant farm workers, including children. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. CTR DIS CONTROL,ATLANTA,GA 30333. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,SCH MED,LEXINGTON,KY 40536. CALIF DEPT HLTH SERV,BERKELEY,CA 94704. US EPA,ATMOSPHER RES & EXPOSURE ASSESSMENT LAB,RES TRIANGLE PK,NC 27711. CALIF DEPT PESTICIDE REGULAT,SACRAMENTO,CA. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. E CAROLINA UNIV,SCH MED,DIV CLIN TOXICOL,GREENVILLE,NC 27834. NCI,ROCKVILLE,MD. RP MOSES, M (reprint author), MIGRANT FARMWORKER HLTH STUDY,POB 420870,SAN FRANCISCO,CA 94142, USA. RI Zahm, Shelia/B-5025-2015 NR 233 TC 79 Z9 87 U1 3 U2 15 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP-OCT PY 1993 VL 9 IS 5 BP 913 EP 959 PG 47 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MW434 UT WOS:A1993MW43400011 PM 8184449 ER PT J AU BLOMER, IE COTTLERFOX, M AF BLOMER, IE COTTLERFOX, M TI OPTIMIZING CONDITIONS FOR HEMATOPOIETIC PROGENITOR-STEM CELL-SURVIVAL DURING LIQUID MARROW STORAGE OR TRANSPORT SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,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 SEP PY 1993 VL 33 IS 9 SU S BP S44 EP S44 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700169 ER PT J AU CIPOLONE, K COTTLERFOX, M AF CIPOLONE, K COTTLERFOX, M TI INITIATING A QUALITY ASSURANCE PROGRAM IN MARROW PROCESSING SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,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 SEP PY 1993 VL 33 IS 9 SU S BP S91 EP S91 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700347 ER PT J AU ETKIN, V JETT, B MAY, F LOWE, C STEC, N LOY, D SINK, B GRAMMONT, R CARTER, C LEONARD, K AF ETKIN, V JETT, B MAY, F LOWE, C STEC, N LOY, D SINK, B GRAMMONT, R CARTER, C LEONARD, K TI A TOTAL QUALITY MANAGEMENT APPROACH TO THE DEVELOPMENT OF STANDARDIZED POLICIES AND PROCEDURES FOR EXPERIMENTAL RESEARCH TRANSFUSION PRODUCTS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT TRANSFUS MED,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 SEP PY 1993 VL 33 IS 9 SU S BP S88 EP S88 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700336 ER PT J AU LEITMAN, SF ROSENBERG, SA AF LEITMAN, SF ROSENBERG, SA TI UNUSUAL HYPERSENSITIVITY REACTIONS TO ALBUMIN IN PATIENTS UNDERGOING PLASMA-EXCHANGE CONDITIONING PRIOR TO IMMUNOTHERAPY SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,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 SEP PY 1993 VL 33 IS 9 SU S BP S4 EP S4 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700011 ER PT J AU MOSLEY, JW MIMMS, LT HOLLINGER, FB STEVENS, CE AACH, RD SPRONK, A SOLOMON, L BARBOSA, LH AF MOSLEY, JW MIMMS, LT HOLLINGER, FB STEVENS, CE AACH, RD SPRONK, A SOLOMON, L BARBOSA, LH TI ANTI-HBC DONOR SCREENING AND HEPATITIS-B IN RECIPIENTS SO TRANSFUSION LA English DT Meeting Abstract C1 ABBOTT LABS,TRANSFUS TRANSMITTED VIRUSES STUDY,N CHICAGO,IL 60064. NHLBI,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 SEP PY 1993 VL 33 IS 9 SU S BP S31 EP S31 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700116 ER PT J AU STRAMER, SL DILLENDER, MJ COLEMAN, CL TEGTMEIER, GE CONTOREGGI, C MEYER, WA FANG, CT AF STRAMER, SL DILLENDER, MJ COLEMAN, CL TEGTMEIER, GE CONTOREGGI, C MEYER, WA FANG, CT TI DETECTION OF ANTIBODIES TO HTLV-I AND HTLV-II IN HIGH-RISK AND ENDEMIC POPULATIONS USING AN HTLV-I EIA SO TRANSFUSION LA English DT Meeting Abstract C1 ABBOTT LABS,N CHICAGO,IL 60064. COMMUNITY BLOOD CTR GREATER KANSAS CITY,KANSAS CITY,MO. NIDA,BALTIMORE,MD. MARYLAND MED LABS,BALTIMORE,MD. AMER RED CROSS,ROCKVILLE,MD. 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 SEP PY 1993 VL 33 IS 9 SU S BP S39 EP S39 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700148 ER PT J AU YU, M COTTLERFOX, M AF YU, M COTTLERFOX, M TI QUALITY ASSURANCE IN FLOW-CYTOMETRY - COMPARISON OF METHODS FOR QUANTIFYING CD-34+ PROGENITOR CELLS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,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 SEP PY 1993 VL 33 IS 9 SU S BP S44 EP S44 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700168 ER PT J AU SCHULICK, RD WEIR, MB MILLER, MW COHEN, DJ BERMAS, BL SHEARER, GM AF SCHULICK, RD WEIR, MB MILLER, MW COHEN, DJ BERMAS, BL SHEARER, GM TI LONGITUDINAL-STUDY OF IN-VITRO CD4+ T-HELPER CELL-FUNCTION IN RECENTLY TRANSPLANTED RENAL-ALLOGRAFT PATIENTS UNDERGOING TAPERING OF THEIR IMMUNOSUPPRESSIVE DRUGS SO TRANSPLANTATION LA English DT Article ID ACUTE REJECTION; CYCLOSPORINE; RECIPIENTS; NEPHROTOXICITY; LYMPHOCYTES; ACTIVATION; RESPONSES; PATHWAYS; ASSAY AB Three distinct T helper activation pathways contribute to interleukin-2 production by human peripheral blood mononuclear cells following in vitro stimulation with HLA alloantigens in a mixed lymphocyte reaction. These pathways involve both CD4+ and CD8+ T helper cells, as well as self and allogeneic antigen-presenting cells. The pathways are differentially susceptible to cyclosporine in vitro, with the CD4+ T helper cell and selfAPC (CD4 approximately sAPC) pathway being the most sensitive. Furthermore, these pathways are differentially susceptible to immunosuppressive drugs in renal allograft patients, and by functional analysis of these pathways we have identified patients who are at increased risk for rejection of their kidney allografts. The present report provides a longitudinal study of the functional T helper cell status of recently transplanted renal allograft recipients undergoing tapering of their immunosuppressive drugs by testing the ability of recipient PBMC to generate IL-2 in response to pathway-specific stimuli. This study provides evidence that IL-2 generation by T helper pathways is dynamic, fluctuating independently of the commonly followed clinical parameters used to assess graft function and degree of immunosuppression. Significantly, the function of the CD4 approximately sAPC activation pathway correlates with risk of acute rejection. As such, we suggest that periodic assessment of pathway specific T helper function is a more sensitive index for the detection of subtherapeutic dosing of immunosuppressives-and, in particular, for assessing cyclosporine maintenance requirements. Monitoring of pathway specific activity with appropriate cyclosporine dosing adjustments might prevent the initiation of the rejection process and reduce a major source of late graft failure. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21201. RP SCHULICK, RD (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 24 TC 28 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP PY 1993 VL 56 IS 3 BP 590 EP 596 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA LZ870 UT WOS:A1993LZ87000019 PM 8105569 ER PT J AU SIMONDS, WF MANJI, HK GARRITSEN, A AF SIMONDS, WF MANJI, HK GARRITSEN, A TI G-PROTEINS AND BARK - A NEW TWIST FOR THE COILED-COIL SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; BETA-GAMMA-SUBUNITS; DEPENDENT PHOSPHORYLATION RP SIMONDS, WF (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892, USA. NR 12 TC 32 Z9 32 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 SEP PY 1993 VL 18 IS 9 BP 315 EP 317 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LW818 UT WOS:A1993LW81800002 PM 8236449 ER PT J AU WALTHER, MM ALEXANDER, RB WEISS, GH VENZON, D BERMAN, A PASS, HI LINEHAN, WM ROSENBERG, SA AF WALTHER, MM ALEXANDER, RB WEISS, GH VENZON, D BERMAN, A PASS, HI LINEHAN, WM ROSENBERG, SA TI CYTOREDUCTIVE SURGERY PRIOR TO INTERLEUKIN-2-BASED THERAPY IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA SO UROLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; CONTINUOUS-INFUSION INTERLEUKIN-2; RECOMBINANT HUMAN INTERLEUKIN-2; HIGH-DOSE INTERLEUKIN-2; II CLINICAL-TRIAL; PHASE-II; ADOPTIVE IMMUNOTHERAPY; SPONTANEOUS REGRESSION; ALPHA-INTERFERON; ADVANCED CANCER AB From May 1985 to December 1990, 93 patients with the clinical diagnosis of metastatic renal cell carcinoma and their primary tumor in place were evaluated for cytoreductive surgery as preparation for systemic therapy with regimens based on interleukin-2. These patients had typical sites of metastatic disease and manifestations of paraneoplastic syndromes. Patients underwent removal of the primary tumor, as well as debulking when this could be performed safely. Thirty-two percent of patients (30/93) had a second surgical resection in addition to their nephrectomy, frequently because of the large size of the primary tumor and its invasion of adjacent structures. Thirteen percent of patients (12/93) experienced postoperative complications. There were no perioperative mortalities. Forty percent of patients (37/93) who underwent nephrectomy could not be treated with immunotherapy, usually because of progression of disease. A preoperative ECOG status greater than or equal to 2 was the only significant risk factor associated with failure to undergo immunotherapy (P = 0.043). The response rate to immunotherapy in the 56 patients receiving interleukin-2 was 27 percent (4 CR, 11 PR). C1 NCI,DIV CANC TREATMENT,BIOSTAT SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP WALTHER, MM (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 38 TC 55 Z9 55 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1993 VL 42 IS 3 BP 250 EP 258 DI 10.1016/0090-4295(93)90612-E PG 9 WC Urology & Nephrology SC Urology & Nephrology GA LX672 UT WOS:A1993LX67200004 PM 8379024 ER PT J AU REHM, S LIJINSKY, W THOMAS, BJ KASPRZAK, BH AF REHM, S LIJINSKY, W THOMAS, BJ KASPRZAK, BH TI CLARA CELL ANTIGEN IN NORMAL AND MIGRATORY DYSPLASTIC CLARA CELLS, AND BRONCHIOLOALVEOLAR CARCINOMA OF SYRIAN-HAMSTERS INDUCED BY N-NITROSOMETHYL-N-HEPTYLAMINE SO VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY LA English DT Article DE SYRIAN HAMSTER; CLARA CELL; IMMUNOGOLD; LUNG CANCER; SURFACTANT APOPROTEIN-A ID LUNG-CANCER; EPITHELIAL-CELLS; HISTOLOGIC CHARACTERIZATION; BRONCHIAL EPITHELIUM; ALVEOLAR CARCINOMA; SECRETORY PROTEIN; GOLDEN-HAMSTERS; INDUCED INJURY; TUMORS; EXPRESSION AB Histogenetic features of lung tumours were studied in Syrian hamsters that had been induced with 6.8 mg N-nitrosomethyl-n-heptylamine/animal by gavage once a week for 35 weeks. At intervals from experimental week 2 until week 46, pulmonary tissues from hamsters were examined by light and electron microscopy. This report describes early hyperplastic lesions associated with terminal bronchioles and the progression of these lesions to bronchioloalveolar tumours. Using immunohistochemical and ultrastructural colloidal gold labelling techniques, hamster Clara cell antigen was found to be localized in Clara cell granules and smooth endoplasmic reticulum of normal cells, in dysplastic Clara cells migrating through basement membrane defects or from the open end of terminal bronchioles, and in hyperplastic peribronchiolar cell foci. The latter progressed to bronchioloalveolar tumours growing out along alveolar basement membranes in a characteristic lace-like, lepidic pattern. Tumours were composed of secretory (Clara), ciliated, mucous, and undifferentiated cells, as well as trapped, non-neoplastic alveolar type II cells. Hyperplastic neuroendocrine cell foci lining airways were immunoreactive for chromogranin, but these cells did not participate in the pre-neoplastic or neoplastic process. It is suggested that bronchioloalveolar carcinomas in hamsters are derived from bronchiolar secretory (Clara) cells growing along alveolar walls, differentiating into other bronchiolar cell types and entrapping resident alveolar type II cells. Due to the migratory capacity of Clara cells, it is also possible for tumours composed of bronchiolar cells to develop at the lung periphery. C1 NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. NCI,FCRDC,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP REHM, S (reprint author), NCI,FCRDC,PROGRAM RESOURCES INC DYNCORP,BLDG 538,RM 220,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 66 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6075 J9 VIRCHOWS ARCH B JI Virchows Arch. B-Cell Molec. Pathol. PD SEP PY 1993 VL 64 IS 3 BP 181 EP 190 DI 10.1007/BF02915111 PG 10 WC Pathology SC Pathology GA LY392 UT WOS:A1993LY39200007 PM 8242177 ER PT J AU BHAT, NK ADACHI, Y SAMUEL, KP DERSE, D AF BHAT, NK ADACHI, Y SAMUEL, KP DERSE, D TI HTLV-1 GENE-EXPRESSION BY DEFECTIVE PROVIRUSES IN AN INFECTED T-CELL LINE SO VIROLOGY LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; RNA RESPONSE ELEMENTS; VIRAL MESSENGER-RNA; LEUKEMIA-VIRUS; LYMPHOTROPIC VIRUS; TRANSCRIPTIONAL ACTIVATOR; REGULATORY PROTEINS; REX TRANSACTIVATOR; MOLECULAR-BIOLOGY C1 NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS INC,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. RP BHAT, NK (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 57 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP PY 1993 VL 196 IS 1 BP 15 EP 24 DI 10.1006/viro.1993.1450 PG 10 WC Virology SC Virology GA LT255 UT WOS:A1993LT25500002 PM 8356792 ER PT J AU KLASSE, PJ MCKEATING, JA SCHUTTEN, M REITZ, MS ROBERTGUROFF, M AF KLASSE, PJ MCKEATING, JA SCHUTTEN, M REITZ, MS ROBERTGUROFF, M TI AN IMMUNE-SELECTED POINT MUTATION IN THE TRANSMEMBRANE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HXB2-ENV-ALA 582(-] THR)) DECREASES VIRAL NEUTRALIZATION BY MONOCLONAL-ANTIBODIES TO THE CD4-BINDING SITE SO VIROLOGY LA English DT Note ID CD4 BINDING; SOLUBLE CD4; CELL-FUSION; I GP120; HIV-1; EPITOPE; GLYCOPROTEIN; GENERATION; INFECTION; AFFINITY C1 LUND UNIV,INST MED MICROBIOL,S-22101 LUND,SWEDEN. NATL INST PUBL HLTH & ENVIRONM PROTECT,IMMUNOBIOL LAB,BILTHOVEN,NETHERLANDS. NIH,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP KLASSE, PJ (reprint author), INST CANC RES,CHESTER BEATTY LABS,237 FULHAM RD,LONDON SW3 6JB,ENGLAND. NR 33 TC 35 Z9 35 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 SEP PY 1993 VL 196 IS 1 BP 332 EP 337 DI 10.1006/viro.1993.1484 PG 6 WC Virology SC Virology GA LT255 UT WOS:A1993LT25500036 PM 8356803 ER PT J AU KOONIN, EV SENKEVICH, TG AF KOONIN, EV SENKEVICH, TG TI FOWLPOX VIRUS ENCODES A PROTEIN RELATED TO HUMAN DEOXYCYTIDINE KINASE - FURTHER EVIDENCE FOR INDEPENDENT ACQUISITION OF GENES FOR ENZYMES OF NUCLEOTIDE-METABOLISM BY DIFFERENT VIRUSES SO VIRUS GENES LA English DT Article DE FOWLPOX VIRUS; VACCINIA VIRUS; DEOXYCYTIDINE KINASE; HERPESVIRUSES; VIRUS EVOLUTION ID VACCINIA VIRUS; THYMIDYLATE KINASE; THYMIDINE KINASE; ADENYLATE KINASE; SEQUENCE; BINDING; EVOLUTION; EXPRESSION; HERPES; REGION AB It is demonstrated that fowlpox virus (FPV) protein FP26 located in the HindIII D fragment of the genome is related to the human deoxycytidine kinase (dCK) and probably possesses the same enzymatic activity. A homologous protein is not encoded by vaccinia virus. A multiple alignment of the amino acid sequences of the human and FPV dCKs, the thymidine kinases (TK) of herpesviruses, and cellular and vaccinia virus thymidylate kinases (ThyK) was generated and the conserved motifs, at least two of which are implicated in ATP binding, were characterized. An apparent duplication of ATP-binding motif B in the dCKs was revealed, leading to the reassignment of one of the catalytic residues. Phylogenetic analysis based on the multiple alignment suggested that the putative dCK of FPV probably has diverged from the common ancestor with the human dCK at a later stage of evolution than the herpesvirus TKs, with the ThyKs being peripheral members of the family. These results are compatible with the hypothesis that genes for enzymes of nucleotide metabolism could be acquired independently by different DNA viruses (Koonin, E.V. and Senkevich, T.G., Virus Genes 6:187-196, 1992). C1 RUSSIAN ACAD MED SCI,INST VIRAL PREPARAT,MOSCOW,RUSSIA. RP KOONIN, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 24 TC 7 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD SEP PY 1993 VL 7 IS 3 BP 289 EP 295 DI 10.1007/BF01702589 PG 7 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA MC626 UT WOS:A1993MC62600007 PM 8279127 ER PT J AU BENCHEKROUN, MN PARKER, R REED, E SINHA, BK AF BENCHEKROUN, MN PARKER, R REED, E SINHA, BK TI INHIBITION OF DNA-REPAIR AND SENSITIZATION OF CISPLATIN IN HUMAN OVARIAN-CARCINOMA CELLS BY INTERLEUKIN-1-ALPHA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PLATINUM; QUANTITATION; CHEMOTHERAPY; SPECTROMETRY C1 NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BLDG 10,ROOM 6N-119,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NR 19 TC 16 Z9 16 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 AUG 31 PY 1993 VL 195 IS 1 BP 294 EP 300 DI 10.1006/bbrc.1993.2044 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LU459 UT WOS:A1993LU45900045 PM 8363610 ER PT J AU SORSCHER, SM STEEG, P FERAMISCO, JR BUCKMASTER, C BOSS, GR MEINKOTH, J AF SORSCHER, SM STEEG, P FERAMISCO, JR BUCKMASTER, C BOSS, GR MEINKOTH, J TI MICROINJECTION OF AN NM23 SPECIFIC ANTIBODY INHIBITS CELL-DIVISION IN RAT EMBRYO FIBROBLASTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE-KINASE; MICROTUBULE ASSEMBLY INVITRO; NUCLEOTIDE-BINDING-PROTEINS; DUCTAL BREAST CARCINOMAS; IMP DEHYDROGENASE; TUMOR-METASTASIS; GENE-EXPRESSION; GOOD PROGNOSIS; ACUTE-LEUKEMIA; DROSOPHILA C1 UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. NCI,PATHOL LAB,BETHESDA,MD 20892. RP SORSCHER, SM (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093, USA. NR 55 TC 18 Z9 18 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 AUG 31 PY 1993 VL 195 IS 1 BP 336 EP 345 DI 10.1006/bbrc.1993.2049 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LU459 UT WOS:A1993LU45900050 PM 8395830 ER PT J AU BHAT, MK PARKISON, C MCPHIE, P LIANG, CM CHENG, SY AF BHAT, MK PARKISON, C MCPHIE, P LIANG, CM CHENG, SY TI CONFORMATIONAL-CHANGES OF HUMAN BETA-1-THYROID HORMONE-RECEPTOR INDUCED BY BINDING OF 3,3',5-TRIIODO-L-THYRONINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID THYROID-HORMONE; NUCLEAR RECEPTOR; AUXILIARY PROTEIN; DNA; ANTIBODIES C1 NCI,DCBDC,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,37-4B09,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. ONCOLOGIX,GAITHERSBURG,MD 20878. NR 13 TC 36 Z9 36 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 AUG 31 PY 1993 VL 195 IS 1 BP 385 EP 392 DI 10.1006/bbrc.1993.2055 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LU459 UT WOS:A1993LU45900056 PM 8363616 ER PT J AU YOO, SH LEWIS, MS AF YOO, SH LEWIS, MS TI DIMERIZATION AND TETRAMERIZATION PROPERTIES OF THE C-TERMINAL REGION OF CHROMOGRANIN-A - A THERMODYNAMIC ANALYSIS SO BIOCHEMISTRY LA English DT Article ID SECRETORY PROTEIN-I; MESSENGER-RNA; SARCOPLASMIC-RETICULUM; CONFORMATIONAL CHANGE; SECRETOGRANIN-II; ADRENAL-MEDULLA; COIL TRANSITION; PH; BINDING; RAT AB Chromogranin A, which is a high-capacity, low-affinity Ca2+ binding protein, has recently been shown to exist in monomer-dimer and in monomer-tetramer equilibria at pH 7.5 and 5.5, respectively [Yoo, S. H., & Lewis, M. S. (1992) J. Biol. Chem. 267,11236-11241]. The pH appeared to be a necessary and sufficient factor determining the types of oligomer formed. In the present study, using 14 synthetic peptides representing various portions of chromogranin A, we have identified a region in chromogranin A which exhibited dimerization and tetramerization properties at pH 7.5 and 5.5, respectively. Of the 14 peptides, only the conserved C-terminal region (residues 407-431), represented by peptide 14, showed the oligomerization property, existing in a dimeric state at pH 7.5 and in a tetrameric state at pH 5.5. The DELTAG-degrees values of tetramerization were approximately -18.0 kcal/mol, and the DELTAG-degrees value of dimerization was -4.6 kcal/mol. Although peptide 14 represented only 6% of the entire sequence, the DELTAG-degrees value of -18.0 kcal/mol accounted for 80-83% of the DELTAG-degrees values (-21.6 to -22.7 kcal/mol) of tetramerization of intact chromogranin A. Unlike the tetramerization mechanisms of intact chromogranin A where the presence of 35 mM Ca2+ changed the tetramerization mechanism from an enthalpically driven to an entropically driven reaction, the tetramerization mechanism of peptide 14 remained entropically driven regardless of the presence of Ca2+. Likewise, dimerization of the peptide was also entropically driven. From these results, it was suggested that the conserved C-terminal region has an intrinsic ability to form a dimer at pH 7.5 and a tetramer at pH 5.5 with little or no conformational changes. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP YOO, SH (reprint author), NIDCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-15,BETHESDA,MD 20892, USA. NR 40 TC 33 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 31 PY 1993 VL 32 IS 34 BP 8816 EP 8822 DI 10.1021/bi00085a012 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV971 UT WOS:A1993LV97100012 PM 8364029 ER PT J AU LETEURTRE, F FESEN, M KOHLHAGEN, G KOHN, KW POMMIER, Y AF LETEURTRE, F FESEN, M KOHLHAGEN, G KOHN, KW POMMIER, Y TI SPECIFIC INTERACTION OF CAMPTOTHECIN, A TOPOISOMERASE-I INHIBITOR, WITH GUANINE RESIDUES OF DNA DETECTED BY PHOTOACTIVATION AT 365 NM SO BIOCHEMISTRY LA English DT Article ID SEQUENCE REQUIREMENTS; DEOXYRIBONUCLEIC-ACID; BIOLOGICAL-ACTIVITY; ANTITUMOR-ACTIVITY; NITROGEN MUSTARDS; SINGLET OXYGEN; NUCLEIC-ACIDS; CLEAVAGE; BINDING; DERIVATIVES AB Camptothecin-induced DNA photolesions were examined after UVA irradiation at 365 nm. DNA single-strand breaks were induced both in supercoiled and in relaxed SV40 DNA. In uniquely end-labeled human c-myc DNA, camptothecin-induced cleavage occurred exclusively at guanines and was markedly enhanced by hot piperidine treatment. Runs of polyguanines were the most cleaved, especially in their 5' flank. Primer extension experiments in the absence of piperidine treatment confirmed these results and did not show additional lesions. We found that synthetic single-stranded oligonucleotides were more reactive than duplex oligonucleotides. In addition, an excess of dideoxyguanosine triphosphates competed for camptothecin-induced DNA photolesions. Therefore, camptothecin stacking in DNA grooves is more likely than genuine drug intercalation. Groove shielding with sodium or magnesium reduced camptothecin-induced photodamage while minor groove occupancy with spermine extended damages. Photolesion mechanisms were investigated using scavengers. In aerobic conditions, the most effective scavengers were thiourea, sodium azide, and catalase. Protection by superoxide dismutase was weak, and mannitol was ineffective. In anaerobic conditions, lesions were more extensive. Taken together, these results show that photoactivated camptothecin interacts specifically and intimately with guanines. This finding is consistent with preferential stimulation of topoisomerase I cleavage at sites that bear a guanine at their 5'-DNA terminus [Jaxel, C., et al. (1991) J. Biol. Chem. 266,1465-1469] and with the camptothecin stacking model at topoisomerase I DNA cleavage sites. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892. NR 50 TC 50 Z9 50 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 31 PY 1993 VL 32 IS 34 BP 8955 EP 8962 DI 10.1021/bi00085a029 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV971 UT WOS:A1993LV97100029 PM 8395887 ER PT J AU HOSHINO, T UEKAMA, K PITHA, J AF HOSHINO, T UEKAMA, K PITHA, J TI INCREASE IN TEMPERATURE ENHANCES SOLUBILITY OF DRUGS IN AQUEOUS-SOLUTIONS OF HYDROXYPROPYLCYCLODEXTRINS SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Note DE HYDROXYPROPYLCYCLODEXTRIN; DRUG SOLUBILIZATION; DRUG PREPARATION; HYDROXYPROPYLCYCLODEXTRIN COMPLEX; TEMPERATURE EFFECT ID CIRCULAR-DICHROISM; CYCLODEXTRINS; COMPLEXES; DERIVATIVES; ETHANOL AB The solubilities of carbamazepine, dexamethasone, and griseofulvin in aqueous media were synergistically increased with increasing hydroxypropylcyclodextrin concentration and with increasing temperature. The results suggest that the increase in free drug concentration from solution heating counterbalances the simultaneously occurring dissociation of the drug-hydroxypropylcyclodextrin complexes. From a practical point of view, the results show that heating or heat-sterilization may be useful steps in the preparation of hydroxvpropylcyclodextrin-based pharmaceutical formulations. C1 NIA,GRC,4940 EASTERN AVE,BALTIMORE,MD 21224. KUMAMOTO UNIV,FAC PHARMACEUT SCI,KUMAMOTO 862,JAPAN. RI Uekama, Kaneto/G-9890-2011 NR 16 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD AUG 31 PY 1993 VL 98 IS 1-3 BP 239 EP 242 DI 10.1016/0378-5173(93)90063-L PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT725 UT WOS:A1993LT72500030 ER PT J AU VORECHOVSKY, I ZHOU, JN HAMMARSTROM, L SMITH, CIE THOMAS, JD PAUL, WE NOTARANGELO, LD BERNATOWSKAMATUSZKIEWICZ, E AF VORECHOVSKY, I ZHOU, JN HAMMARSTROM, L SMITH, CIE THOMAS, JD PAUL, WE NOTARANGELO, LD BERNATOWSKAMATUSZKIEWICZ, E TI ABSENCE OF XID MUTATION IN X-LINKED AGAMMAGLOBULINEMIA SO LANCET LA English DT Letter C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PAEDIAT,BRESCIA,ITALY. CHILDRENS MEM HOSP,DEPT CLIN IMMUNOL,WARSAW,POLAND. RP VORECHOVSKY, I (reprint author), KAROLINSKA INST NOVUM,CTR BIOTECHNOL,S-14157 HUDDINGE,SWEDEN. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 8 TC 7 Z9 7 U1 0 U2 6 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 28 PY 1993 VL 342 IS 8870 BP 552 EP 552 DI 10.1016/0140-6736(93)91676-D PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LU582 UT WOS:A1993LU58200040 PM 8102684 ER PT J AU LEROITH, D ROBERTS, CT AF LEROITH, D ROBERTS, CT TI INSULIN-LIKE GROWTH-FACTORS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FACTOR-I GENE; START SITE USAGE; MESSENGER-RNAS; IGF-I; LEADER EXONS; FUNCTIONAL-ANALYSIS; SOMATOMEDIN-C; SEQUENCE; LIVER; RECEPTOR C1 NIDDKD, DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT, BLDG 10,ROOM 8S-239, BETHESDA, MD 20892 USA. NR 44 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 1 EP 9 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100001 ER PT J AU LEROITH, D WERNER, H FARIA, TN KATO, H ADAMO, M ROBERTS, CT AF LEROITH, D WERNER, H FARIA, TN KATO, H ADAMO, M ROBERTS, CT TI INSULIN-LIKE GROWTH-FACTOR RECEPTORS - IMPLICATIONS FOR NERVOUS-SYSTEM FUNCTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FACTOR-I RECEPTOR; COOH-TERMINAL TRUNCATION; IGF-I; GENE-EXPRESSION; CELL-CULTURES; RAT; BINDING; BRAIN; LOCALIZATION; DOMAIN RP LEROITH, D (reprint author), NIDDKD, DIABET BRANCH, BLDG 10, ROOM 8S239, BETHESDA, MD 20892 USA. NR 40 TC 0 Z9 0 U1 1 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 22 EP 32 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100003 ER PT J AU BONDY, CA LEE, WH AF BONDY, CA LEE, WH TI PATTERNS OF INSULIN-LIKE GROWTH-FACTOR AND IGF RECEPTOR GENE-EXPRESSION IN THE BRAIN - FUNCTIONAL IMPLICATIONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; FACTOR-I; RAT-BRAIN; MESSENGER-RNA; INSITU HYBRIDIZATION; POSTNATAL-DEVELOPMENT; GLUCOSE-UTILIZATION; CELLULAR-PATTERN; THYROID-HORMONE; PITUITARY-GLAND RP BONDY, CA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 43 TC 6 Z9 6 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 33 EP 43 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100004 ER PT J AU GUROFF, G AF GUROFF, G TI NERVE GROWTH-FACTOR AS A NEUROTROPHIC AGENT SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INDUCED NEURITE OUTGROWTH; FACTOR-INDUCED INCREASE; TRK PROTOONCOGENE PRODUCT; PROTEIN-KINASE INHIBITOR; ELONGATION FACTOR-II; PC12 CELLS; FACTOR RECEPTORS; TYROSINE PHOSPHORYLATION; PHEOCHROMOCYTOMA CELLS; CALCIUM-UPTAKE RP GUROFF, G (reprint author), NICHHD, GROWTH FACTORS SECT, BLDG 49, ROOM 5A64, BETHESDA, MD 20892 USA. NR 100 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 51 EP 59 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100006 ER PT J AU ADAMO, ML SHEMER, J ROBERTS, CT LEROITH, D AF ADAMO, ML SHEMER, J ROBERTS, CT LEROITH, D TI INSULIN AND INSULIN-LIKE GROWTH FACTOR-I INDUCED PHOSPHORYLATION IN NEURALLY DERIVED CELLS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RECEPTOR GENE-EXPRESSION; TYROSINE KINASE-ACTIVITY; NEURO-BLASTOMA CELLS; RAT-BRAIN; IGF-I; AUTORADIOGRAPHIC LOCALIZATION; ENDOGENOUS SUBSTRATE; CELLULAR-PATTERN; TRANSGENIC MICE C1 NIDDKD, MOLEC & CELLULAR PHYSIOL SECT, DIABET BRANCH, BETHESDA, MD 20892 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 113 EP 125 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100011 ER PT J AU PERFETTI, R SHULDINER, AR AF PERFETTI, R SHULDINER, AR TI INSULIN, BUT NOT INSULIN-LIKE GROWTH FACTOR-I, IS EXPRESSED DURING EARLY NERVOUS-SYSTEM DEVELOPMENT IN PREPANCREATIC XENOPUS-EMBRYOS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID LAEVIS; GENES C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 27 PY 1993 VL 692 BP 268 EP 269 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA261 UT WOS:A1993MA26100031 ER PT J AU BAKER, TA MIZUUCHI, M SAVILAHTI, H MIZUUCHI, K AF BAKER, TA MIZUUCHI, M SAVILAHTI, H MIZUUCHI, K TI DIVISION-OF-LABOR AMONG MONOMERS WITHIN THE MU-TRANSPOSASE TETRAMER SO CELL LA English DT Article ID DNA STRAND-TRANSFER; P ELEMENT TRANSPOSITION; BACTERIOPHAGE-MU; B-PROTEIN; PHAGE-MU; INVITRO TRANSPOSITION; A-PROTEIN; CLEAVAGE; SITE; ENDS AB A single tetramer of Mu transposase (MuA) pairs the recombination sites, cleaves the donor DNA, and joins these ends to a target DNA by strand transfer. Analysis of C-terminal deletion derivatives of MuA reveals that a 30 amino acid region between residues 575 and 605 is critical for these three steps. Although inactive on its own, a deletion protein lacking this region assembles with the wild-type protein. These mixed tetramers carry out donor cleavage but do not promote strand transfer, even when the donor cleavage stage is by-passed. These data suggest that the active center of the transposase is composed of the C-terminus of four MuA monomers; one dimer carries out donor cleavage while all four monomers contribute to strand transfer. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 40 TC 95 Z9 95 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 27 PY 1993 VL 74 IS 4 BP 723 EP 733 DI 10.1016/0092-8674(93)90519-V PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LU592 UT WOS:A1993LU59200015 PM 8395353 ER PT J AU FERRARIS, JD AF FERRARIS, JD TI MOLECULAR APPROACHES TO THE STUDY OF EVOLUTION AND PHYLOGENY OF THE NEMERTINA SO HYDROBIOLOGIA LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL MEETING ON NEMERTEAN BIOLOGY CY AUG 10-15, 1991 CL BANGOR, WALES DE GENE EXPRESSION; NUCLEOTIDE SEQUENCE; INVERTEBRATE ID MITOCHONDRIAL-DNA SEQUENCES; POLYMERASE CHAIN-REACTION; ENZYMATIC AMPLIFICATION; VOLUME REGULATION; INTERTIDAL NEMERTINE; ALDOSE REDUCTASE; AMPLIFIED DNA; RIBOSOMAL-RNA; CELLS; NACL AB Molecular biological tools currently available to us are revolutionizing the way in which we can address questions in evolutionary biology. The purpose of this article is to provide an overview of molecular techniques and applications available to biologists who are interested in evolutionary studies but who have little acquaintance with molecular biology. In evolutionary biology, techniques designed to determine degree of nucleic acid similarity are in common use and will be dealt with first. Another approach, namely gene expression studies, has strong implications for evolutionary biology but generally requires substantial familiarity with molecular biological tools. Expression studies provide powerful tools for discerning processes of speciation, as in the selection of genetic variants, as well as discerning lineages, e.g., expression of specific homeobox genes during segment formation. For investigations where either nucleic acid identity or gene expression are the ultimate goal, detailed information, protocols and appropriate controls are beyond the scope of this work but, where possible, recent review articles are cited. RP FERRARIS, JD (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 51 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-8158 J9 HYDROBIOLOGIA JI Hydrobiologia PD AUG 27 PY 1993 VL 266 IS 1-3 BP 255 EP 265 DI 10.1007/BF00013373 PG 11 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA LZ117 UT WOS:A1993LZ11700020 ER PT J AU HORUK, R CHITNIS, CE DARBONNE, WC COLBY, TJ RYBICKI, A HADLEY, TJ MILLER, LH AF HORUK, R CHITNIS, CE DARBONNE, WC COLBY, TJ RYBICKI, A HADLEY, TJ MILLER, LH TI A RECEPTOR FOR THE MALARIAL PARASITE PLASMODIUM-VIVAX - THE ERYTHROCYTE CHEMOKINE RECEPTOR SO SCIENCE LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; KNOWLESI MALARIA; CYTOKINE FAMILY; SPECIFICITY; ANTIGEN; PROTEIN AB Plasmodium vivax and P. falciparum are the major causes of human malaria, except in sub-Saharan Africa where people lack the Duffy blood group antigen, the erythrocyte receptor for P. vivax. Duffy negative human erythrocytes are resistant to invasion by P. vivax and the related monkey malaria, P. knowlesi. Several lines of evidence in the present study indicate that the Duffy blood group antigen is the erythrocyte receptor for the chemokines interleukin-8 (IL-8) and melanoma growth stimulatory activity (MGSA). First, IL-8 binds minimally to Duffy negative erythrocytes. Second, a monoclonal antibody to the Duffy blood group antigen blocked binding of IL-8 and other chemokines to Duffy positive erythrocytes. Third, both MGSA and IL-8 blocked the binding of the parasite ligand and the invasion of human erythrocytes by P. knowlesi, suggesting the possibility of receptor blockade for anti-malarial therapy. C1 NIH,MALARIA RES LAB,BETHESDA,MD 20892. MONTEFIORE MED CTR,BRONX,NY 10467. JG BROWN CANC CTR,DIV MED ONCOL HEMATOL,LOUISVILLE,KY 40292. RP HORUK, R (reprint author), GENENTECH INC,S SAN FRANCISCO,CA 94080, USA. FU NHLBI NIH HHS [HL 41382] NR 27 TC 413 Z9 422 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 27 PY 1993 VL 261 IS 5125 BP 1182 EP 1184 DI 10.1126/science.7689250 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LU586 UT WOS:A1993LU58600036 PM 7689250 ER PT J AU DEMATTEIS, MA SANTINI, G KAHN, RA DITULLIO, G LUINI, A AF DEMATTEIS, MA SANTINI, G KAHN, RA DITULLIO, G LUINI, A TI RECEPTOR AND PROTEIN KINASE-C-MEDIATED REGULATION OF ARF BINDING TO THE GOLGI-COMPLEX SO NATURE LA English DT Article ID ADP-RIBOSYLATION FACTOR; BREFELDIN-A; GUANINE-NUCLEOTIDE; COATED VESICLES; CELL-SURFACE; BETA-COP; SECRETION; INHIBITION; TRANSPORT; MEMBRANES AB THE formation of constitutive transport vesicles involves the association of non-clathrin coat proteins to transport organelles1,2 . Here we report that IgE receptors and protein kinase C (PKC) regulate the GTP-dependent binding of the two coat proteins ADP-ribosylation factor (ARF) and beta-COP3-5 to Golgi membranes in rat basophilic leukaemia cells. Activation of IgE receptors and PKC prevented the ARF and beta-COP dissociation from Golgi membranes that occurs in permeabilized cells in the absence of GTP and potentiated the association-promoting effects of GTP and the G protein activator fluoroaluminate. In contrast, PKC downregulation and PKC inhibition abolished the activity of GTP and fluoro-luminate in promoting ARF binding to the Golgi complex. Studies of ARF binding to isolated Golgi membranes gave similiar results. These findings suggest that coat assembly on Golgi membranes, and thus possibly constitutive secretory traffic, is modulated by membrane receptors and second messengers. C1 IST RIC FARMACOL MARIO NEGRI,CONSORZIO MARIO NEGRI SUD,MOLEC NEUROBIOL LAB,I-66030 SANTA MARIA IMBAR,ITALY. NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP DEMATTEIS, MA (reprint author), IST RIC FARMACOL MARIO NEGRI,CONSORZIO MARIO NEGRI SUD,PHYSIOPATHOL SECRET UNIT,I-66030 SANTA MARIA IMBAR,ITALY. RI Luini, Alberto/L-1372-2013 OI Luini, Alberto/0000-0002-8729-2549 NR 36 TC 137 Z9 140 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 26 PY 1993 VL 364 IS 6440 BP 818 EP 821 DI 10.1038/364818a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LU581 UT WOS:A1993LU58100060 PM 7689177 ER PT J AU IBARAKI, K ROBEY, PG YOUNG, MF AF IBARAKI, K ROBEY, PG YOUNG, MF TI PARTIAL CHARACTERIZATION OF A NOVEL GGA-FACTOR WHICH BINDS TO THE OSTEONECTIN PROMOTER IN BOVINE BONE-CELLS SO GENE LA English DT Article DE DNASE-I FOOTPRINTING; TRANSCRIPTION FACTORS; PURINE-RICH SEQUENCE; UV-CROSS-LINKING ID C-MYC PROMOTER; TRANSCRIPTION INITIATION; EXTRACELLULAR-MATRIX; INSITU HYBRIDIZATION; SEQUENCE-ANALYSIS; SECRETED PROTEIN; MESSENGER-RNA; GENE; SPARC; EXPRESSION AB Osteonectin (On)/SPARC (secreted protein, acidic and rich in cysteine) is a highly conserved extracellular matrix protein found in bone and other tissues throughout vertebrate evolution. In previous studies, approximately 500 bp of DNA 5' to the transcription start point (tsp) and a part of exon 1, including homopurine (R(n))/homopyrimidine (Y(n))-rich sequences (the 'GGA box' and its complements), was demonstrated to be important in upregulation of On gene expression in a cell-specific manner. The purpose of this study was to decipher the transcriptional regulation of On through its cis- and trans-acting elements. DNase I footprinting analysis indicated protein binding which may be related to the transcriptional factors, AP2, SP1 and a novel 'GGA' factor which binds to the 3' end of the promoter (-286 to +43 to the tsp). Comparisons of footprinting between nuclear extracts of bone (On-expressing) cells and Madin and Darby bovine kidney (MDBK) (nonexpressing) cells indicate that 'GGA' factor binding to a purine GGGGA/GGA-rich sequence is cell-type specific and therefore may be involved in the cell-specific expression of this gene. From ultraviolet (UV)-crosslinking experiments, this 'GGA' factor was demonstrated to be a single 40-kDa protein. RP IBARAKI, K (reprint author), NIDR,BLDG 30,RM 222,BRB,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 38 TC 14 Z9 15 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 AUG 25 PY 1993 VL 130 IS 2 BP 225 EP 232 DI 10.1016/0378-1119(93)90423-Z PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LV583 UT WOS:A1993LV58300009 PM 8359689 ER PT J AU SAX, CM STOVER, DM ILAGAN, JG ZEHNER, ZE PIATIGORSKY, J AF SAX, CM STOVER, DM ILAGAN, JG ZEHNER, ZE PIATIGORSKY, J TI FUNCTIONAL-ANALYSIS OF CHICKEN VIMENTIN DISTAL PROMOTER REGIONS IN CULTURED LENS CELLS SO GENE LA English DT Note DE RECOMBINANT DNA; GENE EXPRESSION; CAT; INTERMEDIATE FILAMENTS; TRANSCRIPTION; BETA-GALACTOSIDASE; ACTIVATOR; REPRESSOR ID GENE-EXPRESSION; DNA-BINDING; C-MYC; TRANSCRIPTIONAL ENHANCER; PROTEIN-BINDING; OCULAR LENS; ELEMENTS; CLONING; ASSAY AB Synthesis of the cytoskeletal intermediate filament protein vimentin (Vim) in the lens is unexpected due to the mesenchymal preference of Vim-encoding gene (Vim) expression and the epithelial origin of the lens. Previous studies indicated that chicken Vim gene expression in cultured lens cells is regulated by both positive- and negative-acting sequence elements within the first -767 nucleotides (nt) of its promoter. Here, we demonstrate the existence of additional upstream chicken Vim promoter elements which function in transfected lens cells. Sequences within the nt -1360/ -1156 region repressed promoter activity in transfected lens cells to levels lower than that observed for the previously defined more proximal repressor elements. The -1612/-1360 region activated promoter activity to levels similar to those observed for the strongest previously defined proximal promoter. The nt sequence analysis of the upstream promoter region revealed the presence of multiple consensus repressor and activator transcription-factor-binding sites. Several of these sites have been implicated for lens expression of enzyme-crystallin-encoding genes (cry), suggesting that Vim expression may share features with the cry genes for recruitment and high-level expression in the lens. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA 23298. RP SAX, CM (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 208,900 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL45422] NR 40 TC 5 Z9 5 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 AUG 25 PY 1993 VL 130 IS 2 BP 277 EP 281 DI 10.1016/0378-1119(93)90431-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LV583 UT WOS:A1993LV58300017 PM 8359695 ER PT J AU DANCIGER, M KOZAK, CA SUZUKI, S SUZUKI, S CHANG, MR SHINOHARA, T FARBER, DB AF DANCIGER, M KOZAK, CA SUZUKI, S SUZUKI, S CHANG, MR SHINOHARA, T FARBER, DB TI TRANSCRIPTION FACTOR-IID PROBES LOCALIZE A SINGLE-GENE TO THE PROXIMAL REGION OF MOUSE CHROMOSOME-17 SO GENE LA English DT Note DE MOUSE GTF2D; HUMAN GTF2D; GENE MAPPING; TRANSCRIPTION INITIATION, GENOMIC AND CDNA CLONING; RETINAL PHOTORECEPTORS; SOMATIC CELL HYBRIDS; MULTILOCUS TEST-CROSS LINKAGE ANALYSIS ID S-ANTIGEN GENE; BINDING-PROTEIN; TATA; EXPRESSION; ACTIVATION; SEQUENCES; RHODOPSIN; PROMOTER; DOMAINS; COMPLEX AB We have used a 5' fragment of the gene GTF2D, which encodes human transcription factor IID, and Chinese hamster-mouse somatic cell hybrids to map the murine homologue, Gtf2d, to a single locus on mouse chromosome 17 (Chr 17). Linkage analysis of progeny from an interspecific backcross localized the gene near the marker D17Leh66 in the proximal region of Chr 17. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT OPHTHALMOL, LOS ANGELES, CA 90024 USA. LOYOLA MARYMOUNT UNIV, DEPT BIOL, LOS ANGELES, CA 90045 USA. NIAID, LMM, BETHESDA, MD 20892 USA. NEI, RETINAL CELL & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP DANCIGER, M (reprint author), UNIV CALIF LOS ANGELES, SCH MED, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. OI Shinohara, Toshimichi/0000-0002-7197-9039 FU NEI NIH HHS [EY 00331, EY 08285] NR 21 TC 2 Z9 2 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 AUG 25 PY 1993 VL 130 IS 2 BP 283 EP 286 DI 10.1016/0378-1119(93)90432-3 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA LV583 UT WOS:A1993LV58300018 PM 8359696 ER PT J AU HOU, EW LI, SSL AF HOU, EW LI, SSL TI SEQUENCE-ANALYSIS OF MOUSE CDNAS ENCODING RIBOSOMAL-PROTEINS L12 AND L18 SO GENE LA English DT Note DE RIBOSOMES; RAT; XENOPUS; GENOMIC ORGANIZATION; PSEUDOGENES ID PROCESSED PSEUDOGENES; EXPRESSED GENE; FAMILY; IDENTIFICATION AB Mouse cDNAs encoding ribosomal proteins (r-proteins), L12 and L18, were isolated and their sequences determined. The L12 cDNA was found to contain 639 bp, including a coding sequence of 498 nucleotides (nt), 5' (78 nt) and 3' (45 nt) untranslated regions (UTRs), and a poly(A) tail of 18 nt. The L18 cDNA was shown to consist of 648 bp, including a coding sequence of 567 nt, 5' (26 nt) and 3' (39 nt) UTRs, and a poly(A) tail of 16 nt. The nt sequences of the protein-coding region from the mouse L12 and L18 cDNAs were found to exhibit 96% and 92% identity, respectively, with those of the rat. With the use of mouse L12 and L18 cDNA probes, multiple (at least 10) copies of the L12 and L18 gene families were shown to be present in the mouse and rat genomes. However, there was no sequence heterogeneity detected among seven L18 cDNA clones, indicating that only one copy of the L18 gene-related sequences is functional, and the other copies are presumably nonfunctional pseudogenes. The complete amino acid (aa) sequences of the mouse r-proteins, L12 and L18, were deduced from the nt sequences of their cDNA clones. L12 has 165 aa and a M(r) of 17790, while L18 has 188 aa and a M(r) of 21 570. The aa sequences of the mouse r-proteins, L12 and L18, exhibit 98% and 94% identity, respectively, to those of rat. C1 NIEHS,GENET LAB,MAIL DROP D3-05,POB 12233,RES TRIANGLE PK,NC 27709. NR 15 TC 4 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 AUG 25 PY 1993 VL 130 IS 2 BP 287 EP 290 DI 10.1016/0378-1119(93)90433-4 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA LV583 UT WOS:A1993LV58300019 PM 8359697 ER PT J AU ATKINSON, RL DIETZ, WH FOREYT, JP GOODWIN, NJ HILL, JO HIRSCH, J PISUNYER, FX WEINSIER, RL WING, R YANOVSKI, SZ HUBBARD, VS HOOFNAGLE, JH AF ATKINSON, RL DIETZ, WH FOREYT, JP GOODWIN, NJ HILL, JO HIRSCH, J PISUNYER, FX WEINSIER, RL WING, R YANOVSKI, SZ HUBBARD, VS HOOFNAGLE, JH TI VERY-LOW-CALORIE DIETS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID SPARING-MODIFIED FAST; RESTING METABOLIC-RATE; LONG-TERM EVALUATION; WEIGHT-LOSS; FOLLOW-UP; BODY-COMPOSITION; BEHAVIOR-THERAPY; OBESE PATIENTS; INPATIENT-OUTPATIENT; GALLSTONE FORMATION AB Objective.-To provide an overview of the published scientific information on the safety and efficacy of very low-calorie diets (VLCDs) and to provide rational recommendations for their use. Data Sources and Extraction.-Original reports obtained through a MEDLINE search for 1966 through 1992 on VLCDs or reducing diets plus obesity, supplemented by a manual search of bibliographies and the opinions of experts in the field of nutrition and weight loss therapy for obesity. Only studies of humans were cited. Data Synthesis.-Current VLCDs are usually provided in the context of comprehensive treatment programs, during which usual food intake is completely replaced by specific foods or liquid formulas containing 3350 kJ/d (800 kcal/d) or less. Weight loss on VLCDs averages 1.5 to 2.5 kg/wk; total loss after 12 to 16 weeks averages 20 kg. These results are superior to standard low-calorie diets of 5020 kJ/d (1200 kcal/d), which lead to weight losses of 0.4 to 0.5 kg/wk and an average total loss of only 6 to 8 kg. There is little evidence that intakes of less than 3350 kJ/d (800 kcal/d) result in better weight losses than 3350 kJ. Intake of at least 1 g/kg of ideal body weight per day of protein of high biologic value appears to be important in helping to preserve lean body mass. Serious complications of modern VLCDs are unusual, cholelithiasis being most common. Conclusions.-Current VLCDs are generally safe when used under proper medical supervision in moderately and severely obese patients (body mass index [weight in kilograms divided by height in meters squared] >30) and are usually effective in promoting significant short-term weight loss, with concomitant improvement in obesity-related conditions. Long-term maintenance of weight lost with VLCDs is not very satisfactory and is no better than with other forms of obesity treatment. Incorporation of behavioral therapy and physical activity in VLCD treatment programs seems to improve maintenance. C1 NIDDKD,DIV DIGEST DIS & NUTR,BLDG 31,ROOM 9A23,BETHESDA,MD 20892. DEPT VET AFFAIRS,HAMPTON,VA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. BAYLOR COLL MED,HOUSTON,TX 77030. HLTH WATCH,INFORMAT & PROMOT SERV,NEW YORK,NY. VANDERBILT UNIV,NASHVILLE,TN 37240. ROCKEFELLER UNIV,NEW YORK,NY 10021. COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,NEW YORK,NY 10027. UNIV ALABAMA,BIRMINGHAM,AL 35294. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. RI Biguzzi, Felipe/E-4724-2015; OI Atkinson, Richard L./0000-0003-1745-5645 NR 121 TC 138 Z9 142 U1 6 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 25 PY 1993 VL 270 IS 8 BP 967 EP 974 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA LT567 UT WOS:A1993LT56700028 ER PT J AU PHILPOTT, CC HAILE, D ROUAULT, TA KLAUSNER, RD AF PHILPOTT, CC HAILE, D ROUAULT, TA KLAUSNER, RD TI MODIFICATION OF A FREE FE-S CLUSTER CYSTEINE RESIDUE IN THE ACTIVE IRON-RESPONSIVE ELEMENT-BINDING PROTEIN PREVENTS RNA-BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SULFUR CLUSTER; ACONITASE ACTIVITY; IRE-BP; INVITRO; MECHANISM; CRYSTAL AB The iron-responsive element-binding protein (IRE-BP) binds to specific RNA stem-loop structures called iron-responsive elements (IREs), which mediate the post-transcriptional regulation of a variety of genes involved in iron metabolism. The IRE-BP is cytosolic aconitase, and a [4Fe-4S] cubane cluster is required for aconitase activity but is associated with loss of IRE binding affinity. Chemical modification of the IRE-BP can abrogate RNA binding and the 3 cysteines predicted to coordinate the Fe-S cluster in the IRE-BP could be targets for modification. We report the expression of recombinant IRE-BP in which the three putative cluster cysteines (Cys-437, Cys-503, and Cys-506) have been mutated to serine residues. Replacement of any or all of these cysteine residues results in a complete loss of aconitase activity. While all of the mutants bind RNA, substitution of Cys-437 specifically renders the IRE-BP resistant to inactivation by low concentrations of N-ethylmaleimide or diamide. These results identify Cys-437 as the target of in vitro regulation of RNA binding in the IRE-BP and suggest that, in the RNA-binding form of the protein, Cys-437 is free and therefore available for modifications that inhibit RNA binding. C1 NICHHD,CELL BIOL & METAB BRANCH,BLDG 18T,RM 101,BETHESDA,MD 20892. NR 27 TC 90 Z9 89 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 AUG 25 PY 1993 VL 268 IS 24 BP 17655 EP 17658 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300002 PM 8349646 ER PT J AU SATOH, S NISHIMURA, H CLARK, AE KOZKA, IJ VANNUCCI, SJ SIMPSON, IA QUON, MJ CUSHMAN, SW HOLMAN, GD AF SATOH, S NISHIMURA, H CLARK, AE KOZKA, IJ VANNUCCI, SJ SIMPSON, IA QUON, MJ CUSHMAN, SW HOLMAN, GD TI USE OF BISMANNOSE PHOTOLABEL TO ELUCIDATE INSULIN-REGULATED GLUT4 SUBCELLULAR TRAFFICKING KINETICS IN RAT ADIPOSE-CELLS - EVIDENCE THAT EXOCYTOSIS IS A CRITICAL SITE OF HORMONE ACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; GLUCOSE-TRANSPORT ACTIVITY; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; STIMULATED TRANSLOCATION; PHORBOL ESTER; PHOSPHORYLATION STATE; HEXOSE TRANSPORTERS; SURFACE; ISOPROTERENOL AB The subcellular trafficking of tracer-tagged GLUT4 between the plasma membranes and low-density microsomes of rat adipose cells has been studied. Cell-surface GLUT4 have been initially tracer-tagged in the insulin-stimulated state with the [H-3]bismannose photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos-4-yloxy)-2-propylamine. The half-time for internalization of tracer-tagged GLUT4 when insulin is removed by collagenase treatment is similar to that observed for the decrease in immunodetectable GLUT4 in the plasma membranes and the decrease in glucose transport activity in the intact cells. In contrast, internalization of tracer-tagged GLUT4 also occurs when cells are maintained in the continuous presence of insulin even though the plasma membrane level of immunodetectable GLUT4 and glucose transport activity in the intact cells are unaltered. These data show, for the first time, that insulin has little, if any, effect on the rate constant for GLUT4 endocytosis, but instead, primarily increases the rate constant for exocytosis. Tracer-tagged GLUT4 that is returned to the low-density microsomes can be restimulated with fresh insulin to recycle to the plasma membranes and to a steady-state distribution level that is the same as that observed in cells that are maintained in the continuous presence of insulin. These data suggest that the cells' entire complement of GLUT4 is involved in the recycling process. Following insulin stimulation of adipose cells initially in the basal state, the increase in immunodetectable GLUT4 in the plasma membranes precedes the increase in accessibility of GLUT4 to exofacial 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4-yloxy)-2-propylamine photolabeling, and this in turn precedes the increase in cellular glucose transport activity. Such time course data suggest that there may be plasma membrane intermediate states in the GLUT4 trafficking pathway. The kinetic properties of GLUT4 translocation and its recycling have been interpreted in terms of a subcellular trafficking model that identifies exocytosis, possibly involving-hypothetical ''docking'' and ''fusion'' steps, as the critical site of hormone action. C1 NIDDKD,EXPTL DIABET METAB & NUTR SECT,BLDG 10,RM 5N102,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,RECEPTORS & HORMONE ACT SECT,BETHESDA,MD 20892. UNIV BATH,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 44 TC 254 Z9 257 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 AUG 25 PY 1993 VL 268 IS 24 BP 17820 EP 17829 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300030 PM 8349666 ER PT J AU TAKADA, T IIDA, K MOSS, J AF TAKADA, T IIDA, K MOSS, J TI CLONING AND SITE-DIRECTED MUTAGENESIS OF HUMAN ADP-RIBOSYLARGININE HYDROLASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGATION-INDEPENDENT CLONING; GLUTATHIONE-S-TRANSFERASE; TURKEY ERYTHROCYTES; SKELETAL-MUSCLE; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; PROTEIN; RIBOSYLTRANSFERASE; PURIFICATION; NAD AB Mono-ADP-ribosylation of arginine is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the opposing reactions in the cycle. ADP-ribosylarginine hydrolases differ in their dithiothreitol (DTT) requirements. Rat and mouse hydrolases require DTT for maximal activity, but calf, guinea pig, and human hydrolases are DTT-independent. To define the molecular basis for these differences, brain ADP-ribosylarginine hydrolases were cloned. Deduced amino acid sequences of mouse and rat hydrolases were 94% identical with 5 conserved cysteines. The human hydrolase sequence was 83% identical to that of rat but contained only 4 cysteines with cysteine 108 in rat corresponding to serine 103 in human. To investigate the role of rat cysteine 108, human and rat wild-type hydrolases and mutants, in which serine 103 in human was replaced by cysteine (S103C) and cysteine 108 in rat was replaced by serine (C108S), were expressed in Escherichia coli. Affinity-purified anti-rat brain hydrolase antibodies reacted with recombinant wild-type rat hydrolase, but only weakly with the C108S mutant. They did not react with human wild-type or the S103C mutant. Human hydrolase and rat C108S were DTT-independent; human S103C was, however, DTT-dependent. These data clearly show that cysteine 108 in rat hydrolase plays a critical role in DTT dependence and may be important in immunoreactivity. RP TAKADA, T (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 34 TC 42 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 1993 VL 268 IS 24 BP 17837 EP 17843 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300032 PM 8349667 ER PT J AU HARRISON, EH ROJAS, CJ GAD, MZ KEMPNER, ES AF HARRISON, EH ROJAS, CJ GAD, MZ KEMPNER, ES TI ANALYSIS OF MICROSOMAL CHOLESTERYL ESTER HYDROLASES BY RADIATION INACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOLATED SUBCELLULAR MEMBRANES; RAT-LIVER MICROSOMES; DIFFERENT LABORATORIES; COA HYDROLASE; PURIFICATION; LIPASE; IDENTITY; ENZYMES AB Radiation inactivation by high energy electrons, a method for determining the size of a protein without prior purification, was used to study the acid and neutral cholesteryl ester hydrolase (CEH) activities of rat liver microsomes. The same preparations were also assayed for the microsomal, ''nonspecific' carboxylesterases using o-nitrophenyl acetate as substrate. Nonspecific esterase activity surviving radiation could be fit to a single exponential function, the slope of which yielded a target size of 47 +/- 5 kDa (mean +/- S.D., n = 7). Surviving CEH activity assayed at pH 5 could also be fit to a single exponential that yielded a target size of 71 +/- 14 kDa (n = 5). In contrast, the surviving CEH activity assayed at pH 7 was more complex. The data from six experiments were described as the sum of two exponentials, indicating that most of the activity is due to an entity that is three to four times larger and a minor amount to one that is half the size of the pH 5 enzyme. The results are consistent with the suggestion that the acid and neutral microsomal CEH activities are due to distinct enzymes, which are not the ''nonspecific'' carboxylesterases. Their sizes also differ from those previously determined for lysosomal acid lipase and other lipases in the liver. C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. RP HARRISON, EH (reprint author), MED COLL PENN,DEPT BIOCHEM,2900 QUEEN LANE,PHILADELPHIA,PA 19129, USA. OI Gad, Mohamed/0000-0003-1173-8628 FU NHLBI NIH HHS [HL-22633]; NIDDK NIH HHS [R01 DK044498, DK-44498] NR 24 TC 3 Z9 3 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 AUG 25 PY 1993 VL 268 IS 24 BP 17867 EP 17870 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300036 PM 8349671 ER PT J AU MCDONALD, LJ MOSS, J AF MCDONALD, LJ MOSS, J TI NITRIC OXIDE-INDEPENDENT, THIOL-ASSOCIATED ADP-RIBOSYLATION INACTIVATES ALDEHYDE DEHYDROGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; HUMAN ERYTHROCYTES; SACCHAROMYCES-CEREVISIAE; SKELETAL-MUSCLE; RAT-LIVER; RIBOSE; PROTEINS; MONO(ADP-RIBOSYLATION); INVIVO; FORMS AB Nitric oxide inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase and stimulates NAD-dependent automodification of a cysteine (Dimmeler, S., Lottspeich, F., and Brune, B. (1992) J. Biol. Chem. 267, 16771-16774). Another NAD-utilizing dehydrogenase that has a catalytic cysteine, aldehyde dehydrogenase (ALDH), was also inhibited by nitric oxide. Unlike glyceraldehyde-3-phosphate dehydrogenase, ALDH was modified in a nitric oxide-independent process by ADP-ribose, but not by NAD. Modification, which proceeded to >2 mol ADP-ribose.mol ALDH-1, was associated with an exponential decrease in enzyme activity to less than 10% of control. Two types of evidence suggested modification of the ALDH-active site: 1) ADP-ribose inhibited ALDH competitively (K(i) = 0.46 mM) with respect to NAD (K(m) = 0.11 mm) in brief incubations and 2) the presence of substrates protected ALDH from both modification and inhibition by ADP-ribose. The ALDH-ADP-ribose bond was sensitive to base and mercuric ion and stable to acid and neutral hydroxylamine, properties shared with the ADP-ribosylcysteine linkage synthesized enzymatically by pertussis toxin. These data demonstrate a novel means of inactivation of an NAD-dependent enzyme, namely the affinity-based modification of the enzyme NAD site by ADP-ribose, and suggest that nonenzymatic ADP-ribosylation may be responsible for modification of cysteine residues. RP MCDONALD, LJ (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10-5N-307,BETHESDA,MD 20892, USA. NR 38 TC 36 Z9 36 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 AUG 25 PY 1993 VL 268 IS 24 BP 17878 EP 17882 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300038 PM 8349672 ER PT J AU FERBER, A CHANG, CD SELL, C PTASZNIK, A CRISTOFALO, VJ HUBBARD, K OZER, HL ADAMO, M ROBERTS, CT LEROITH, D DUMENIL, G BASERGA, R AF FERBER, A CHANG, CD SELL, C PTASZNIK, A CRISTOFALO, VJ HUBBARD, K OZER, HL ADAMO, M ROBERTS, CT LEROITH, D DUMENIL, G BASERGA, R TI FAILURE OF SENESCENT HUMAN FIBROBLASTS TO EXPRESS THE INSULIN-LIKE GROWTH FACTOR-I GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; CULTURED HUMAN-FIBROBLASTS; SIMIAN VIRUS-40; SOMATOMEDIN PRODUCTION; CELLULAR SENESCENCE; DNA-SYNTHESIS; T-ANTIGEN; CELLS; IMMORTALIZATION; TRANSLOCATION AB Senescent human diploid fibroblasts express several growth-regulated genes but fail to express others. In this paper we show, by a very sensitive technique (reverse transcriptase-polymerase chain reaction), that senescent cells fail to express insulin-like growth factor-1 (IGF-1) mRNA, which is expressed in moderate amounts by young cells. Human fibroblasts immortalized by transfection with a temperature-sensitive SV40 T antigen gene regain the ability to express IGF-1 mRNA, but only at the permissive temperature of 34-degrees-C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39-degrees-C, the temperature-sensitive T antigen is nonfunctional, IGF-1 RNA is not detectable, and the cells fail to grow even in 10% serum. The failure to express IGF-1 mRNA in postsenescent cells can be ascribed, at least in part, to a transcriptional mechanism. Despite the correlation among immortalization by SV40 T antigen, expression of IGF-1, and growth, it seems unlikely that the failure to express IGF-1 is the sole cause of cellular senescence; other requirements must be postulated. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,BLSB ROOM 624A,PHILADELPHIA,PA 19107. MED COLL PENN,CTR GERONTOL RES,PHILADELPHIA,PA 19129. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT MICROBIOL & MOLEC GENET,NEWARK,NJ 07103. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. FU NIA NIH HHS [AG 04821, AG 00378] NR 35 TC 55 Z9 55 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 AUG 25 PY 1993 VL 268 IS 24 BP 17883 EP 17888 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300039 PM 7688732 ER PT J AU BIRD, GS BURGESS, GM PUTNEY, JW AF BIRD, GS BURGESS, GM PUTNEY, JW TI SULFHYDRYL-REAGENTS AND CAMP-DEPENDENT KINASE INCREASE THE SENSITIVITY OF THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN HEPATOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUINEA-PIG HEPATOCYTES; CALCIUM RELEASE; TRISPHOSPHATE; THIMEROSAL; MOBILIZATION; OSCILLATIONS; VASOPRESSIN; HORMONES; GLUCAGON; THIOL AB Sulfhydryl reagents such as tert-butyl hydroperoxide (TBHP) have been shown to increase cytosolic Ca2+ concentration ([Ca2+]i) in rat hepatocytes in a way that resembles responses to Ca2+-mobilizing hormones (Saikada, I., Thomas, A. P., and Farber, J. L. (1991) J. Biol. Chem. 266, 717-722; Rooney, T. A., Renard, D. C., Sass, E. J., and Thomas, A. P. (1991) J. Biol. Chem. 266, 12272-12282) and to increase the amount of Ca2+ released by inositol 1,4,5-trisphosphate ((1,4,5)IP3) from permeable rat liver cells (Rooney et al., 1991, op. cit.; Missiaen, L., Taylor, C. W., and Berridge, M. J. (1991) Nature 352, 241-244; Renard, D. C., Seitz, M. B., and Thomas, A. P. (1992) Biochem. J. 284, 507-512). The effects of sulfhydryl reagents were studied in fura-2-injected rat and guinea pig hepatocytes and compared with the actions of cAMP (Burgess, G. M., Bird, G. St. J., Obie, J. F., and Putney, J. W., Jr. (1991) J. Biol. Chem. 261, 4772-4781). In rat liver cells, the increases in [Ca2+]i induced by TBHP and thimerosal were prevented by microinjection of the cells with the (1,4,5)IP3 receptor antagonist heparin. In guinea pig hepatocytes, TBHP was not able to increase [Ca2+]i unless the cells were pretreated with angiotensin II to raise endogenous levels of (1,4,5)IP3 or were first injected with a sub-threshold concentration of inositol 2,4,5-trisphosphate ((2,4,5)IP3). The responses to TBHP in (2,4,5)IP3-injected guinea pig cells were also blocked by heparin. In many respects, the actions of TBHP appeared to be similar to those of cAMP, which has previously been shown to increase sensitivity to (1,4,5)IP3 in intact guinea pig hepatocytes (Burgess et al., 1991, op. cit.). TBHP also mimicked the effect of cAMP-dependent kinase (PKA) in permeabilized guinea pig hepatocytes by increasing the amount of Ca2+ released by (1,4,5)IP3. The responses to TBHP and cAMP in (2,4,5)IP3-injected guinea pig hepatocytes differed, however, in that the increase in [Ca2+]i evoked by elevating intracellular cAMP was greatly reduced by Wiptide, an inhibitor of PKA, while Wiptide had no effect on the Ca2+ transients induced by TBHP. This provides evidence that the sensitizing effect of TBHP is not mediated by PKA and is more likely to be a direct effect on the inositol trisphosphate receptor. It is possible, however, that the sulfhydryl reagents and PKA act on a common regulatory site on the receptor protein. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709. SANDOZ INST MED RES,LONDON WC1E 6BN,ENGLAND. NR 27 TC 95 Z9 95 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 AUG 25 PY 1993 VL 268 IS 24 BP 17917 EP 17923 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300044 PM 8394353 ER PT J AU MARGOLESE, L WANECK, GL SUZUKI, CK DEGEN, E FLAVELL, RA WILLIAMS, DB AF MARGOLESE, L WANECK, GL SUZUKI, CK DEGEN, E FLAVELL, RA WILLIAMS, DB TI IDENTIFICATION OF THE REGION ON THE CLASS-I HISTOCOMPATIBILITY MOLECULE THAT INTERACTS WITH THE MOLECULAR CHAPERONE, P88 (CALNEXIN, IP90) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHAIN BINDING-PROTEIN; ENDOPLASMIC-RETICULUM MEMBRANE; VIRUS-G-PROTEIN; HEAVY-CHAIN; T-CELL; INTRACELLULAR-TRANSPORT; SURFACE EXPRESSION; PEPTIDE-BINDING; QA-2 ANTIGEN; BETA-2-MICROGLOBULIN AB During early stages in their biogenesis, murine class I histocompatibility molecules interact transiently with a molecular chaperone of the endoplasmic reticulum designated p88. Using a series of mutant class I heavy chains we mapped the region of the heavy chain that interacts with p88. Domain deletion mutants of the H-2D(b) and H-2K(b) molecules revealed that most of the extracellular portion of the heavy chain and the bulk of the cytoplasmic domain were not required for the association. However, replacement of the transmembrane segment and cytoplasmic domain with a glycosyl phosphatidylinositol anchor from Q7b resulted in a heavy chain that was incapable of interaction with p88. These results suggested that the primary site of interaction with p88 is within a region containing the transmembrane segment and several flanking amino acids of the class I heavy chain. This finding was supported by replacing the glycosyl phosphatidylinositol anchor of the noninteracting Q7b protein with segments of the D(b) heavy chain containing the putative interaction site and showing that the hybrids were capable of associating with p88. The apparent lack of interaction between segments of p88 and the class I heavy chain that are present within the lumen of the endoplasmic reticulum was also observed when the association between p88 and the a chain of the T cell receptor was examined. The full-length transmembrane a chain formed a complex with p88, whereas a soluble variant consisting of most of the luminal portion of the alpha chain exhibited only minimal interaction. Thus, p88 is capable of associating with nascent integral membrane proteins through transmembrane interactions that are unavailable to the major soluble chaperone of the endoplasmic reticulum, BiP (GRP78). C1 UNIV TORONTO,DEPT BIOCHEM,MED SCI BLDG,TORONTO M5S 1A8,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02129. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. FU NIGMS NIH HHS [GM46467] NR 56 TC 78 Z9 78 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 AUG 25 PY 1993 VL 268 IS 24 BP 17959 EP 17966 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300050 PM 8349678 ER PT J AU KULESZALIPKA, D BRZESKA, H BAINES, IC KORN, ED AF KULESZALIPKA, D BRZESKA, H BAINES, IC KORN, ED TI AUTOPHOSPHORYLATION-INDEPENDENT ACTIVATION OF ACANTHAMOEBA MYOSIN-I HEAVY-CHAIN KINASE BY PLASMA-MEMBRANES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-BINDING; COFACTOR PROTEIN; 3RD ISOFORM; CASTELLANII; PURIFICATION; LOCALIZATION; PHOSPHORYLATION; ATPASE; CLEAVAGE; SITES AB The three isoforms of Acanthamoeba myosin I (non-filamentous myosin with only a single heavy chain) express actin-activated Mg2+-ATPase activity only when phosphorylated at a single site by myosin I heavy chain kinase. The kinase is activated by autophosphorylation that is greatly stimulated by acidic phospholipids. Substantial fractions of the three myosins I and the kinase are associated in situ with membranes, and all four enzymes bind to purified membranes in vitro. We now report that when kinase and myosin I are incubated together with phosphatidylserine vesicles not only does the kinase autophosphorylate more rapidly than soluble kinase in the absence of phosphatidylserine but that, probably as a result, the kinase phosphorylates myosin I more rapidly than soluble kinase phosphorylates soluble myosin I. Similarly, plasma membrane-bound kinase phosphorylates membrane-bound myosin I and activates its actin-activated Mg2+-ATPase activity more rapidly than soluble kinase phosphorylates and activates soluble myosin I in the absence of membranes. However, the enhanced activity of membrane-bound kinase (which is comparable to the activity of kinase in the presence of phosphatidylserine) is not due to autophosphorylation of the membrane-bound kinase, which is very much slower than for kinase activated by phosphatidylserine vesicles. C1 NHLBI, CELL BIOL LAB, BLDG 3, RM B1-22, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 41 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 1993 VL 268 IS 24 BP 17995 EP 18001 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300055 PM 8394357 ER PT J AU TAKIMOTO, M TOMONAGA, T MATUNIS, M AVIGAN, M KRUTZSCH, H DREYFUSS, G LEVENS, D AF TAKIMOTO, M TOMONAGA, T MATUNIS, M AVIGAN, M KRUTZSCH, H DREYFUSS, G LEVENS, D TI SPECIFIC BINDING OF HETEROGENEOUS RIBONUCLEOPROTEIN PARTICLE PROTEIN-K TO THE HUMAN C-MYC PROMOTER, IN-VITRO SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; TRANSCRIPTION FACTOR; GENE-TRANSCRIPTION; TRANS-ACTIVATION; BURKITT-LYMPHOMA; NUCLEAR FACTOR; 5S RNA; SEQUENCE; EXPRESSION; REGION AB A homopurine/homopyrimidine-like sequence is found 1000-150 base pairs upstream of the human c-myc promoter P1. This element, termed the CT-element, has been shown to augment expression from P1, and it serves as a positive transcriptional element when coupled to a heterologous promoter in vivo and in vitro. Synthetic oligonucleotides comprising this element were used to form DNA-protein complexes in electrophoretic mobility shift assays. By using conventional and affinity methods, 61- and 34-kDa proteins were shown to be associated with these complexes. Amino acid sequence analysis and immunological methods have identified these proteins as heterogeneous ribonucleoprotein particle (hnRNP) proteins K and A1. Surprisingly, hnRNP protein K binds to the pyrimidine-rich strand of the CT-element in a sequence-specific manner as well as to the double-stranded molecule. Cotransfection of vectors encoding hnRNP protein K in the sense or anti-sense orientations with reporter plasmids driven by wild-type or mutant CT-elements demonstrates that hnRNP protein K augments gene expression in a cis-element-dependent manner. Taken together, these results suggest that hnRNP protein K may play a role in the transcriptional regulation of the human c-myc gene. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,PHILADELPHIA,PA 19104. RI Levens, David/C-9216-2009; Takimoto, Masato/D-9653-2012; OI Levens, David/0000-0002-7616-922X; Matunis, Michael/0000-0002-9350-6611 NR 48 TC 166 Z9 167 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 AUG 25 PY 1993 VL 268 IS 24 BP 18249 EP 18258 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300089 PM 8349701 ER PT J AU ARORA, KK FILBURN, CR PEDERSEN, PL AF ARORA, KK FILBURN, CR PEDERSEN, PL TI STRUCTURE-FUNCTION-RELATIONSHIPS IN HEXOKINASE - SITE-DIRECTED MUTATIONAL ANALYSES AND CHARACTERIZATION OF OVEREXPRESSED FRAGMENTS IMPLICATE DIFFERENT FUNCTIONS FOR THE N-TERMINAL AND C-TERMINAL HALVES OF THE ENZYME SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; RAT-BRAIN HEXOKINASE; MITOCHONDRIAL BOUND HEXOKINASE; NOVIKOFF ASCITES TUMOR; CLONED CDNA; INTRACELLULAR-LOCALIZATION; GLUCOSE PHOSPHORYLATION; MAMMALIAN HEXOKINASE; BINDABLE FORM; BINDING AB Hexokinases are comprised of two highly homologous approximately 50-kDa halves and are product-inhibited by glucose-6-P. Four amino acid residues, Ser603, Asp657, Glu708, and Glu742, located in the C-terminal half of the tumor mitochondrial enzyme have been shown to be essential for enzyme function (Arora, K. K., Filburn, C. R., and Pedersen, P. L. (1991) J. Biol. Chem. 266, 5359-5362). Here we have assessed also the role of the N-terminal half of the same enzyme. Site-directed mutagenesis of residues predicted to interact with glucose in the N-terminal half, i.e. Ser155, Asp209, and Glu260, to Ala, have no effect on hexokinase activity. In addition, inhibition by hexose mono- and bisphosphates is unchanged for each of the mutant enzymes. Significantly, the overexpressed N-terminal polypeptide is devoid of catalytic activity but does have the capacity to bind ATP-agarose and be released with ATP and glucose-6-P. In contrast, the overexpressed C-terminal polypeptide is catalytically active and shows the same-product inhibition pattern as the complete 100-kDa parent enzyme. These results emphasize that the N-terminal half of tumor hexokinase is essential neither for catalysis nor product modulation. Rather, the N-terminal half may play another role, perhaps in modulation of the ATP/glucose-6-P-dependent binding of the enzyme to tumor mitochondria or by acting as a spacer between the outer mitochondrial membrane and the C-terminal catalytic unit. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,MOLEC & CELLULAR BIOENERGET LAB,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. FU NCI NIH HHS [CA 32742] NR 42 TC 62 Z9 63 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 AUG 25 PY 1993 VL 268 IS 24 BP 18259 EP 18266 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300090 PM 8349702 ER PT J AU KOH, YC BUCZKO, E DUFAU, ML AF KOH, YC BUCZKO, E DUFAU, ML TI REQUIREMENT OF PHENYLALANINE-343 FOR THE PREFERENTIAL DELTA-4-LYASE VERSUS DELTA-5-LYASE ACTIVITY OF RAT CYP17 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME P-45017-ALPHA; LYASE ACTIVITIES; TESTIS; CDNA; EXPRESSION; SEQUENCE; P45017-ALPHA; HYDROXYLASE; MUTAGENESIS; CELLS AB Site-directed mutagenesis of a domain (amino acids 343-348) within the conserved region of rat CYP17 was performed to investigate species-specific differences between rat and human/bovine DELTA4-versus DELTA5-lyase activity. This domain displays substantial deviations between the rat and human/bovine/pig sequences and includes Arg346, which is known to he essential for DELTA4-lyase (Kitamura, M., Buczko, E., and Dufau, M. L. (1991) Mol. Endocrinol. 5, 1373-1380) and DELTA5-lyase activities. Analysis of the DELTA4-lyase activity of mutant rat CYP17 cDNA expressed in nonsteroidogenic COS-1 cells revealed that substitution of Phe at position 343 in the rat with Ile of the human/bovine sequence resulted in a reduction in DELTA4-lyase activity to levels in the range of the DELTA5-supported reaction. This Phe343 --> Ile mutant Cyp17 did not exhibit changes either in DELTA5-supported lyase activity or in DELTA4- and DELTA5-hydroxylase activities. Substitution of Asn344, Ser347, and His348 in rat CYP17 with the corresponding bovine amino acids Ser, Asn, and Arg did not enhance this effect. Thus, the reduced activity of the bovine CYP17 DELTA4-lyase reaction can be mimicked in part in the rat polypeptide by the substitution of Phe343 with the bovine counterpart, Ile. Unlike the bovine CYP17-catalyzed reaction, the rat Phe343 --> Ile mutant exhibited a low level lyase activity (k(cat)) that did not discriminate between DELTA4- and DELTA5-substrates. These results suggest that the presence of Phe343 enhances the DELTA4-supported lyase activity possibly through stabilization of a DELTA4-specific interaction. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BLDG 49,BETHESDA,MD 20892. NR 21 TC 29 Z9 29 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 AUG 25 PY 1993 VL 268 IS 24 BP 18267 EP 18271 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT743 UT WOS:A1993LT74300091 PM 8349703 ER PT J AU RESZKA, KJ CHIGNELL, CF AF RESZKA, KJ CHIGNELL, CF TI EPR AND SPIN-TRAPPING INVESTIGATION OF FREE-RADICALS FROM THE REACTION OF 4-METHOXYBENZENEDIAZONIUM TETRAFLUOROBORATE WITH MELANIN AND MELANIN PRECURSORS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ONE-ELECTRON TRANSFER; ARENEDIAZONIUM SALTS; REDOX POTENTIALS; AQUEOUS-SOLUTION; MECHANISM; OXYGEN; IONS; SEMIQUINONE; REDUCTION; COMPLEXES AB The interaction of synthetic DOPA melanin (DM) and its precursors (catechols and phenols) with 4-methoxybenzenediazonium tetrafluoroborate (4-MeO-PhN2BF4) has been studied using EPR spectroscopy and the spin-trapping technique. We found that DM, catechol, 3,4-dihydroxybenzoic acid, 3,4-dihydroxyhydrocinnamic acid, 3,4-dihydroxyphenylalanine, and 6-hydroxydopamine all react with 4-MeO-PhN2+ through a one-electron-transfer process which gives rise to an aryl radical (4-MeO-Ph.) derived from the diazonium compound and to radicals from melanin and from the catechol(amine)s. The formation of aryl radicals is an autocatalytic process. To explain the autocatalysis, we postulate a mechanism in which the key step is the formation of o-quinones. In aerated solutions the aryl radicals react with oxygen, which leads to oxygen consumption. The reaction was found to be order 1, 0.5, and 0.35 with respect to 4-MeO-PhN2+, catechol, and oxygen concentration, respectively. Phenol, 4-hydroxyanisole, and tyrosine do not reduce 4-MeO-PhN2+ unless they are activated by the enzyme tyrosinase. In the presence of tyrosinase, tyrosine produces the most efficient reducing agent. This indicates that the conversion of phenols to o-dihydroxybenzene derivatives by tyrosinase is essential for aryl radical formation from 4-MeO-PhN2+. These observations substantiate the ability of hydroquinones and semiquinone radicals to promote the homolysis of diazonium salts to generate aryl radicals. Such reductive activation of diazonium compounds may be pertinent to their biological, mutagenic, and carcinogenic action. RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 36 Z9 36 U1 2 U2 11 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 AUG 25 PY 1993 VL 115 IS 17 BP 7752 EP 7760 DI 10.1021/ja00070a021 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA LW560 UT WOS:A1993LW56000021 ER PT J AU VUISTER, GW BAX, A AF VUISTER, GW BAX, A TI QUANTITATIVE J CORRELATION - A NEW APPROACH FOR MEASURING HOMONUCLEAR 3-BOND J(H(N)H(ALPHA) COUPLING-CONSTANTS IN N-15-ENRICHED PROTEINS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; N-15 CHEMICAL-SHIFTS; TWO-DIMENSIONAL NMR; STAPHYLOCOCCAL NUCLEASE; H-ALPHA; SEQUENTIAL ASSIGNMENTS; ACCURATE MEASUREMENTS; LARGER PROTEINS; SPECTRA; SPECTROSCOPY AB A new approach is described for the measurement of homonuclear H(N)-H(alpha) J couplings in N-15-enriched proteins. The method relies on measurement of the diagonal-peak to cross-peak intensity ratio in a 3D N-15-separated quantitative J-correlation spectrum. The experiment is demonstrated for the protein staphylococcal nuclease, uniformly enriched with N-15, ligated with thymidine 3'-5'-bisphosphate and Ca2+. Amide to C(alpha)H correlations are observed for all but three of the amide protons that have regular intensities in a 2D H-1-N-15 correlation spectrum, and J couplings could be measured for 96 residues with sufficiently resolved H-1-N-15 correlations, including 6 glycines. In addition, for 28 residues with partially overlapping H-1-N-15 correlations, coupling constants can be estimated as small, medium, or large. For 86 out of the 96 residues, the backbone angle phi is known with good precision from the crystal structure, and J values for these residues have a 0.73 Hz root-mean-square deviation from the Karplus curve: J = A cos2(phi - 60) + B cos(phi - 60) + C, where A = 6.51, B = -1.76, C = 1.60. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 46 TC 936 Z9 940 U1 3 U2 31 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 AUG 25 PY 1993 VL 115 IS 17 BP 7772 EP 7777 DI 10.1021/ja00070a024 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA LW560 UT WOS:A1993LW56000024 ER PT J AU TAKAO, M ABRAMIC, M MOOS, M OTRIN, VR WOOTTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M AF TAKAO, M ABRAMIC, M MOOS, M OTRIN, VR WOOTTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M TI A 127 KDA COMPONENT OF A UV-DAMAGED DNA-BINDING COMPLEX, WHICH IS DEFECTIVE IN SOME XERODERMA-PIGMENTOSUM GROUP-E PATIENTS, IS HOMOLOGOUS TO A SLIME-MOLD PROTEIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLEMENTATION GROUP-E; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; MAMMALIAN-CELLS; EXCISION REPAIR; PRIMATE CELLS; MUTATIONS; ACID; PHOTOPRODUCTS; CLONING AB A cDNA which encodes a approximately 127 kDa UV-damaged DNA-binding (UV-DDB) protein with high affinity for (6-4)pyrimidine dimers [Abramic', M., Levine, A.S. & Protic', M., J. Biol. Chem. 266:22493-22500, 1991] has been isolated from a monkey cell cDNA library. The presence of this protein in complexes bound to UV-damaged DNA was confirmed by immunoblotting. The human cognate of the UV-DDB gene was localized to chromosome 11. UV-DDB mRNA was expressed in all human tissues examined, including cells from two patients with xeroderma pigmentosum (group E) that are deficient in UV-DDB activity, which suggests that the binding defect in these cells may reside in a dysfunctional UV-DDB protein. Database searches have revealed significant homology of the UV-DDB protein sequence with partial sequences of yet uncharacterized proteins from Dictyostelium discoideum (44% identity over 529 amino acids) and Oryza sativa (54% identity over 74 residues). According to our results, the UV-DDB polypeptide belongs to a highly conserved, structurally novel family of proteins that may be involved in the early steps of the UV response, e.g., DNA damage recognition. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BLDG 6,RM 1A-15,BETHESDA,MD 20892. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20209. US FDA,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,BETHESDA,MD 20892. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 55 TC 87 Z9 89 U1 0 U2 2 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 AUG 25 PY 1993 VL 21 IS 17 BP 4111 EP 4118 DI 10.1093/nar/21.17.4111 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV915 UT WOS:A1993LV91500027 PM 8371985 ER PT J AU WHITCOMB, JM RASHTCHIAN, A HUGHES, SH AF WHITCOMB, JM RASHTCHIAN, A HUGHES, SH TI A NEW PCR BASED METHOD FOR THE GENERATION OF NESTED DELETIONS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; URACIL DNA GLYCOSYLASE; AMPLIFICATION; CLONING; PRIMER; CDNA AB We have developed a simple, PCR-based protocol, random primed/anchored-PCR (RPA-PCR), that allows the selective amplification and efficient cloning of segments that are adjacent to any known sequence. We demonstrate that RPA-PCR can be used to prepare a nested set of evenly spaced deletions suitable for DNA sequencing. However, it should also be possible to use this technique for a number of other purposes: generating deletions for the analysis of eukaryotic promoters, extending cDNA clones in the 5' direction, cloning the insertion sites of retroviral proviruses and transposons, and analyzing intron/exon boundaries. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. LIFE TECHNOL INC,BRL,GAITHERSBURG,MD 20884. FU NCI NIH HHS [N01-CO-74101] NR 16 TC 2 Z9 6 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 AUG 25 PY 1993 VL 21 IS 17 BP 4143 EP 4146 DI 10.1093/nar/21.17.4143 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV915 UT WOS:A1993LV91500031 PM 7690475 ER PT J AU ADEYEMO, OM YOUDIM, MBH MARKEY, SP MARKEY, CJ POLLARD, HB AF ADEYEMO, OM YOUDIM, MBH MARKEY, SP MARKEY, CJ POLLARD, HB TI L-DEPRENYL CONFERS SPECIFIC PROTECTION AGAINST MPTP-INDUCED PARKINSONS DISEASE-LIKE MOVEMENT DISORDER IN THE GOLDFISH SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE PARKINSONS DISEASE; PYRIDINES; (GOLDFISH) ID MONOAMINE-OXIDASE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; DOPAMINERGIC NEUROTOXICITY; SUPEROXIDE-DISMUTASE; BRAIN; MICE; RAT; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE; NEURONS AB Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, accumulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of movement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectively. The mechanism by which MPTP causes reduced movement in goldfish is to cause an increase in resting time. Otherwise normal average velocity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity during times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and 1-deprenyl is used for treatment of Parkinson's disease in humans. Therefore it is suggested that the evolutionarily equivalent subcortical circuitry and neural density of the goldfish brain may provide a useful model upon which to search for drugs relevant to human Parkinson's disease. C1 TECHNION ISRAEL INST TECHNOL,BRUCE RAPPAPORT FAC MED,DEPT PHARMACOL,HAIFA,ISRAEL. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ADEYEMO, OM (reprint author), NIDDK,LCBG,BLDG 8,BETHESDA,MD 20892, USA. NR 43 TC 12 Z9 14 U1 0 U2 2 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 AUG 24 PY 1993 VL 240 IS 2-3 BP 185 EP 193 DI 10.1016/0014-2999(93)90897-Q PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LV616 UT WOS:A1993LV61600010 PM 8243537 ER PT J AU JACOBOWITZ, DM PALKOVITS, M AF JACOBOWITZ, DM PALKOVITS, M TI THE BIRTH OF NEUROCHEMICAL MAPS - A CITATION-CLASSIC COMMENTARY ON TOPOGRAPHIC ATLAS OF CATECHOLAMINE AND ACETYLCHOLINESTERASE-CONTAINING NEURONS IN THE RAT-BRAIN .1. FOREBRAIN (TELENCEPHALON, DIENCEPHALON) .2. HINDBRAIN (MESENCEPHALON, RHOMBENCEPHALON) BY JACOBOWITZ,D.M., AND PALKOVITS,M. SO CURRENT CONTENTS/LIFE SCIENCES LA English DT Article C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. SEMMELWEIS UNIV MED,SCH MED,NEUROMORPHOL LAB,H-1450 BUDAPEST,HUNGARY. RP JACOBOWITZ, DM (reprint author), NIMH,CLIN SCI LAB,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 4 TC 0 Z9 0 U1 0 U2 2 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0011-3409 J9 CC/LIFE SCI PD AUG 23 PY 1993 IS 34 BP 9 EP 9 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA LQ462 UT WOS:A1993LQ46200002 ER PT J AU HOANG, VQ SUCKLING, KE CHOCHUNG, YS BOTHAM, KM AF HOANG, VQ SUCKLING, KE CHOCHUNG, YS BOTHAM, KM TI THE EFFECT OF CYCLIC-AMP ANALOGS AND GLUCAGON ON CHOLESTERYL ESTER SYNTHESIS AND HYDROLYSIS IN CULTURED HAMSTER HEPATOCYTES SO FEBS LETTERS LA English DT Article DE CHOLESTEROL ESTERIFICATION; CHOLESTERYL ESTER HYDROLYSIS; CYCLIC AMP ANALOG; GLUCAGON; HAMSTER HEPATOCYTE ID HORMONE-SENSITIVE LIPASE; COA REDUCTASE-ACTIVITY; RAT-LIVER CYTOSOL; ACYL-COA; PHOSPHORYLATION-DEPHOSPHORYLATION; PROTEIN-KINASES; MODULATION; ACYLTRANSFERASE; METABOLISM; ACTIVATION AB Two cyclic AMP analogues, 8-chloro cyclic AMP and 8-(4 chlorophenylthio) cyclic AMP, were found to increase the incorporation of [H-3]oleate into cholereryl ester in cultured hamster hapatocytes (30-40%), while incorporation into triaclgycerol was unaffected. An increase of a similar magnitude was observed in the presence of glucagon and the phosphodiesterase inhibitor, theophylline. The cyclic AMP analogues also stimulated the activity of neutral cholesteryl ester hydrolase in the cells, and this effect was mimicked by glucagon and theophylline. These results show that cyclic AMP can affect the cholesteryl ester cycle in hamster hepatocytes, and support the idea that the enzymes involved may be co-ordinately regulated. C1 UNIV LONDON ROYAL VET COLL,DEPT VET BASIC SCI,ROYAL COLL ST,LONDON NW1 0TU,ENGLAND. SMITHKLINE BEECHAM PHARMACEUT,WELWYN GARDEN CIT,HERTS,ENGLAND. NCI,TUMOUR IMMUNOL & DIAG LAB,BETHESDA,MD 20892. NR 31 TC 8 Z9 8 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 AUG 23 PY 1993 VL 329 IS 1-2 BP 17 EP 20 DI 10.1016/0014-5793(93)80183-U PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LT841 UT WOS:A1993LT84100005 PM 8394829 ER PT J AU CUSHMAN, M GOLEBIEWSKI, M MCMAHON, JB HAUGWITZ, RD BADER, JP AF CUSHMAN, M GOLEBIEWSKI, M MCMAHON, JB HAUGWITZ, RD BADER, JP TI DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF COSALANE, A NOVEL ANTI-HIV AGENT WHICH INTERFERES WITH VIRION BINDING AND FUSION EVENTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 1 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102391 ER PT J AU RANDAD, RS PAN, W GULNIK, S BURT, S ERICKSON, JW AF RANDAD, RS PAN, W GULNIK, S BURT, S ERICKSON, JW TI DE-NOVO DESIGN OF NONPEPTIDIC HIV-1 PROTEASE INHIBITORS - INCORPORATION OF BOUND WATER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,PRI DYN CORP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 10 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102400 ER PT J AU DATTA, AK KASPRZAK, KS AF DATTA, AK KASPRZAK, KS TI STUDIES ON THE INDUCTION OF OXIDATIVE DNA-DAMAGE BY FE(II)-HISTIDINE OR FE(III)-HISTIDINE COMPLEXES - RELEVANCE TO CARCINOGENESIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 14 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100891 ER PT J AU GRAGG, CE LOVE, RA MILNE, GWA AF GRAGG, CE LOVE, RA MILNE, GWA TI SPECIAL INTEREST GROUP ON GRAPHICS INTERCHANGE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 AMER CHEM SOC,WASHINGTON,DC 20036. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 21 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100943 ER PT J AU COXON, B POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R AF COXON, B POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R TI THE NMR-SPECTROSCOPY OF OLIGOSACCHARIDES THAT CAN RECOGNIZE A MONOCLONAL ANTI-SHIGELLA-DYSENTERIAE TYPE-1 ANTIBODY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. NICHHD,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 32 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100528 ER PT J AU SCHMIEDEKAMP, AM TOPOL, I BURT, S RAZAFINJANAHARY, H CHERMETTE, H PFALTZGRAFF, T MICHEJDA, C AF SCHMIEDEKAMP, AM TOPOL, I BURT, S RAZAFINJANAHARY, H CHERMETTE, H PFALTZGRAFF, T MICHEJDA, C TI TRIAZENE PROTON AFFINITIES - A COMPARISON BETWEEN DENSITY-FUNCTIONAL, HARTREE-FOCK AND POST-HARTREE-FOCK METHODS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PENN STATE UNIV,ABINGTON,PA 19001. INST PHYS NUCL LYON,LYON,FRANCE. NCI,FCRDC,ABL BRP,FREDERICK,MD 21701. NCI,FCRDC,PRI DYN CORP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 52 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32101306 ER PT J AU ADAMS, HR CHANNING, MA DIVEL, JJ DUNN, BB KIESEWETTER, DO PLASCJAK, P REGDOS, SL SIMPSON, NR ECKELMAN, WC AF ADAMS, HR CHANNING, MA DIVEL, JJ DUNN, BB KIESEWETTER, DO PLASCJAK, P REGDOS, SL SIMPSON, NR ECKELMAN, WC TI TREND ANALYSIS OF LONGITUDINAL QUALITY-CONTROL DATA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT PET,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 54 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200053 ER PT J AU BAHAR, I JERNIGAN, RL AF BAHAR, I JERNIGAN, RL TI CONFORMATIONAL CHARACTERISTICS OF MODEL PROTEINS WITH HOMOGENEOUS AND NONHOMOGENEOUS INTERACTIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. BOGAZICI UNIV,POLYMER RES CTR,DEPT CHEM ENGN,ISTANBUL,TURKEY. RI Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 79 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200831 ER PT J AU PIPPIN, CG GANSOW, OA BRECHBIEL, MW KOCH, L GEERLINGS, MW AF PIPPIN, CG GANSOW, OA BRECHBIEL, MW KOCH, L GEERLINGS, MW TI RECOVERY OF BI-213 FROM AN AC-225 COW - APPLICATION TO THE RADIOLABELING OF MONOCLONAL-ANTIBODIES WITH THE ALPHA-EMITTER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ALPHAMED,AMSTERDAM,NETHERLANDS. NCI,RADIAT ONCOL GRP,CHEM SECT,BETHESDA,MD 20892. INST TRANSURANIUM ELEMENTS,KARLSRUHE,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 94 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200092 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M CASE, RD SHOELSON, SE ROLLER, PP AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M CASE, RD SHOELSON, SE ROLLER, PP TI SYNTHESIS OF PHOSPHONO(DIFLUOROMETHYL) PHENYLALANINE (F2PMP) ANALOGS SUITABLY PROTECTED FOR SOLID-PHASE SYNTHESIS OF SH2 INHIBITORY PEPTIDES CONTAINING PHOSPHOTYROSYL MIMETICS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. HARVARD UNIV,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 106 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102496 ER PT J AU SMYTH, MS STEFANOVA, I HARTMANN, F HORAK, ID OSHEROV, N LEVITZKI, A BURKE, TR AF SMYTH, MS STEFANOVA, I HARTMANN, F HORAK, ID OSHEROV, N LEVITZKI, A BURKE, TR TI NONAMINE-CONTAINING BICYCLIC AND TRICYCLIC ANALOGS OF LAVENDUSTIN A AS PROTEIN-TYROSINE KINASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,DCBDC,METAB BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 107 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102497 ER PT J AU KEMPF, DJ NORBECK, DW MARSH, KC ERICKSON, J AF KEMPF, DJ NORBECK, DW MARSH, KC ERICKSON, J TI DESIGN AND DEVELOPMENT OF SYMMETRY-BASED INHIBITORS OF HIV PROTEASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ABBOTT LABS,DIV PHARMACEUT PROD,ABBOTT PK,IL 60064. NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21701. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 119 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200294 ER PT J AU LEE, J MARQUEZ, VE BLUMBERG, PM LEWIN, NE AF LEE, J MARQUEZ, VE BLUMBERG, PM LEWIN, NE TI A 2,8-DIKETO-1,7-DIOXASPIRO[4.4]NONANE SYSTEM AS A TEMPLATE FOR RIGID DIACYLGLYCEROL ANALOGS AND THEIR INTERACTION WITH PROTEIN-KINASE-C (PK-C) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 126 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102516 ER PT J AU SHARMA, R MARQUEZ, VE MILNE, GWA BLUMBERG, PM LEWIN, NE AF SHARMA, R MARQUEZ, VE MILNE, GWA BLUMBERG, PM LEWIN, NE TI 2,5-DIDEOXY-3-O-TETRADECANOYL-D-GALACTONO-1,4-LACTONE, A HOMOLOG OF 3-O-TETRADECANOYL-2-DEOXY-L-RIBONOLACTONE WITH SUPERIOR BINDING-AFFINITY FOR THE PHORBOL ESTER RECEPTOR OF PROTEIN-KINASE-C (PK-C) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 127 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102517 ER PT J AU ITO, Y SHINOMIYA, K FALES, HM WEISZ, A SCHER, AL AF ITO, Y SHINOMIYA, K FALES, HM WEISZ, A SCHER, AL TI PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY - A NEW PREPARATIVE-SCALE PURIFICATION TECHNIQUE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 154 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100154 ER PT J AU SCHER, AL WEISZ, A ITO, Y AF SCHER, AL WEISZ, A ITO, Y TI EQUILIBRIUM-MODEL FOR PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 155 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100155 ER PT J AU CAI, DG GU, MJ WU, JJ SHAO, RX WU, JZ LI, DP ZHANG, TY ITO, Y AF CAI, DG GU, MJ WU, JJ SHAO, RX WU, JZ LI, DP ZHANG, TY ITO, Y TI SEPARATION AND PURITY ANALYSIS OF THE DIPEPTIDE SWEETENER APM BY HSCCC SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PLA NAVY,PHARM RES CTR,SHANGHAI 200083,PEOPLES R CHINA. PEOPLES LIBERAT ARMY GEN HOSP,NANJING 210002,PEOPLES R CHINA. BEIJING INST NEW TECHNOL APPLICAT,BEIJING 100035,PEOPLES R CHINA. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 158 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100158 ER PT J AU CAI, DG GU, MJ ZHU, GP ZHANG, JD ZHANG, TY ITO, Y AF CAI, DG GU, MJ ZHU, GP ZHANG, JD ZHANG, TY ITO, Y TI SEPARATION OF 3 ALKALOIDS FROM SENECIO-FUBERI HEMSL BY HSCCC SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PLA NAVY,PHARM RES CTR,SHANGHAI 200083,PEOPLES R CHINA. NHLBI,BETHESDA,MD 20892. BEIJING INST NEW TECHNOL APPLICAT,BEIJING 100035,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 165 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100165 ER PT J AU HALLOCK, YF DAI, JR CARDELLINA, JH BOYD, MR AF HALLOCK, YF DAI, JR CARDELLINA, JH BOYD, MR TI LARGE-SCALE ISOLATION OF MICHELLAMINE-B BY CENTRIFUGAL PARTITION CHROMATOGRAPHY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES FACIL,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 169 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100169 ER PT J AU KIESEWETTER, DO ECKELMAN, WC AF KIESEWETTER, DO ECKELMAN, WC TI SYNTHESES OF CHIRAL FLUOROALKYL QUINUCLIDINYL BENZILATES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,WARREN GRANT MAGNUSEN CLIN CTR,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 201 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102591 ER PT J AU FISCHER, B BOYER, JL HOYLE, CHV ZIGANSHIN, AU BRIZZOLARA, AL KNIGHT, GE ZIMMET, J BURNSTOCK, G HARDEN, TK JACOBSON, KA AF FISCHER, B BOYER, JL HOYLE, CHV ZIGANSHIN, AU BRIZZOLARA, AL KNIGHT, GE ZIMMET, J BURNSTOCK, G HARDEN, TK JACOBSON, KA TI NOVEL ATP DERIVATIVES AS POTENT, SELECTIVE P2-PURINOCEPTOR AGONISTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIORGAN CHEM LAB,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27514. UNIV LONDON UNIV COLL,DEPT ANAT & DEV BIOL,LONDON WC1E 6BT,ENGLAND. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 214 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102604 ER PT J AU JI, XD GALLORODRIGUEZ, C JACOBSON, KA AF JI, XD GALLORODRIGUEZ, C JACOBSON, KA TI AN ISOTHIOCYANATE DERIVATIVE OF CAFFEINE AS A SELECTIVE AFFINITY LABEL FOR ADENOSINE-A2 RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,BIORGAN CHEM LAB,BETHESDA,MD 20892. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 215 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102605 ER PT J AU VANBERGEN, AJ VANGALEN, PJM STILES, GL JACOBSON, KA AF VANBERGEN, AJ VANGALEN, PJM STILES, GL JACOBSON, KA TI A3 RECEPTORS - STRUCTURE-ACTIVITY-RELATIONSHIPS AND MOLECULAR MODELING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 217 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102607 ER PT J AU BARCHI, JJ NOMIZU, M ROLLER, PP BURKE, TR AF BARCHI, JJ NOMIZU, M ROLLER, PP BURKE, TR TI SOLUTION STRUCTURE OF A CYCLIC HEXAPEPTIDE DESIGNED AS A CONFORMATIONALLY CONSTRAINED LIGAND FOR THE SH2 DOMAIN OF THE P85 SUBUNIT OF P13 KINASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 220 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32102610 ER PT J AU GRONENBORN, AM VARLEY, P CHRISTENSEN, H WINGFIELD, PT PAIN, RH CLORE, GM AF GRONENBORN, AM VARLEY, P CHRISTENSEN, H WINGFIELD, PT PAIN, RH CLORE, GM TI KINETICS OF FOLDING OF THE ALL BETA-SHEET PROTEIN INTERLEUKIN-1-BETA STUDIED BY NUCLEAR-MAGNETIC-RESONANCE, CIRCULAR-DICHROISM AND FLUORESCENCE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEWCASTLE UPON TYNE,NEWCASTLE NE2 4HH,ENGLAND. NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 240 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200992 ER PT J AU EATON, WA AF EATON, WA TI FAST EVENTS IN PROTEIN-FOLDING INITIATED BY PULSED-LASER PHOTOLYSIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 241 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200993 ER PT J AU VENKATA, T RAO, S NASHED, NT JERINA, DM AF VENKATA, T RAO, S NASHED, NT JERINA, DM TI STERICALLY INDUCED METHOXY MIGRATIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 241 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200415 ER PT J AU HABER, MT NASHED, NT FORBES, BJ LEVIN, W JERINA, DM AF HABER, MT NASHED, NT FORBES, BJ LEVIN, W JERINA, DM TI MICROSOMAL EPOXIDE HYDROLASE-CATALYZED HYDROLYSIS OF K-REGION ARENE OXIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 242 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200416 ER PT J AU BANWELL, MG HAMEL, E IRELAND, NK MACKAY, MF SERELIS, AK AF BANWELL, MG HAMEL, E IRELAND, NK MACKAY, MF SERELIS, AK TI STUDIES DIRECTED TOWARDS TOTAL SYNTHESES OF THE TROPOLOISOQUINOLINE ALKALOIDS GRANDIRUBRINE AND IMERUBRINE .2. THERMOLYSIS OF 8,9-DIHYDRO-2-HYDROXY-3,10,11,12-TETRAMETHOXYISOQUINO[2,1-C][1,2,3]BENZO TRIAZIN-7-IUM CHLORIDE - COMPETITIVE MODES OF CYCLIZATION LEADING TO THE INDENO[1,2,3-IJ]ISOQUINOLINE (AZAFLUORANTHENE) SKELETON SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID IMELUTEINE AB Thermolysis of the title compound 8 produced not only the expected azafluoranthene 7 but also the regioisomeric compound 23 and its dihydro counterpart 22. A mechanism for the formation of compounds 7, 22 and 23 from precursor 8 has been advanced. Reaction of salt 8 with copper bronze in aqueous sulfuric acid produced good yields of dihydroazafluoranthene 29 together with small amounts of the reduction product 30. The tubulin binding properties of the azafluoranthenes 7, 22, 23, 24 and 29 have been determined. C1 NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. ICI DULUX,EXPLORATORY CHEM LABS,CLAYTON,VIC 3168,AUSTRALIA. LA TROBE UNIV,DEPT CHEM,BUNDOORA,VIC 3083,AUSTRALIA. RP BANWELL, MG (reprint author), UNIV MELBOURNE,SCH CHEM,PARKVILLE,VIC 3052,AUSTRALIA. RI Banwell, Martin/H-8354-2014 NR 21 TC 10 Z9 10 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD AUG 21 PY 1993 IS 16 BP 1905 EP 1911 DI 10.1039/p19930001905 PG 7 WC Chemistry, Organic SC Chemistry GA LU723 UT WOS:A1993LU72300014 ER PT J AU HENGGE, UR BROCKMEYER, NH BAUMANN, M REIMANN, G GOOS, M AF HENGGE, UR BROCKMEYER, NH BAUMANN, M REIMANN, G GOOS, M TI LIPOSOMAL DOXORUBICIN IN AIDS-RELATED KAPOSIS-SARCOMA SO LANCET LA English DT Letter C1 UNIV ESSEN GESAMTHSCH,DEPT DERMATOL & VENEREOL,W-4300 ESSEN 1,GERMANY. RP HENGGE, UR (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 32 Z9 32 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 AUG 21 PY 1993 VL 342 IS 8869 BP 497 EP 497 DI 10.1016/0140-6736(93)91624-U PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LU075 UT WOS:A1993LU07500042 PM 8102452 ER PT J AU LINDERS, JTM MONN, JA MATTSON, MV GEORGE, C JACOBSON, AE RICE, KC AF LINDERS, JTM MONN, JA MATTSON, MV GEORGE, C JACOBSON, AE RICE, KC TI SYNTHESIS AND BINDING-PROPERTIES OF MK-801 ISOTHIOCYANATES - (+)-3-ISOTHIOCYANATO-5-METHYL-10,11-DIHYDRO-5H-DIBENZO[A,D]CYCLOHEPTEN-5 ,10-IMINE HYDROCHLORIDE - A NEW, POTENT AND SELECTIVE ELECTROPHILIC AFFINITY LIGAND FOR THE NMDA RECEPTOR-COUPLED PHENCYCLIDINE BINDING-SITE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID AMINO-ACID RECEPTORS; D-ASPARTATE ANTAGONISTS; GUINEA-PIG BRAIN; RAT-BRAIN; ANTICONVULSANT MK-801; SIGMA-RECEPTOR; RECOGNITION SITE; LABELS; INHIBITION; GLUTAMATE AB Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[H-3]-3 binding sites, compared to 20 muM needed for its optical antipode (-)-8a and the 2-isothiocyanate(+)-8b. The apparent K(i) values for reversible inhibition of (+)-[H-3]-3 binding by (+)- and (-)-8a and (+)-8b were 37, 838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[H-3]-3 binding sites at 100 muM and 250 nM, respectively, with apparent K(i) values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 muM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 muM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system. C1 NIDDKD, MED CHEM LAB, BETHESDA, MD 20892 USA. USN, RES LAB, WASHINGTON, DC 20375 USA. RI Fitzmaurice, Richard/C-1508-2008 FU NIAMS NIH HHS [5 F32 AR07980] NR 59 TC 5 Z9 5 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD AUG 20 PY 1993 VL 36 IS 17 BP 2499 EP 2507 DI 10.1021/jm00069a008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA LU544 UT WOS:A1993LU54400008 PM 8355251 ER PT J AU LEE, DC KIM, RY WISTOW, GJ AF LEE, DC KIM, RY WISTOW, GJ TI AN AVIAN ALPHA-B-CRYSTALLIN - NONLENS EXPRESSION AND SEQUENCE SIMILARITIES WITH BOTH SMALL (HSP27) AND LARGE (HSP70) HEAT-SHOCK PROTEINS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE AVIAN ALPHA-B-CRYSTALLIN; NONLENS EXPRESSION; SEQUENCE; HEAT SHOCK PROTEIN ID STRUCTURAL PROTEIN; ATPASE FRAGMENT; COGNATE PROTEIN; EGG ANTIGEN; GENE; ACTIN; EVOLUTION; RNAS; ORGANIZATION; RECRUITMENT C1 NEI, LMDB, MOLEC STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. NR 48 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 20 PY 1993 VL 232 IS 4 BP 1221 EP 1226 DI 10.1006/jmbi.1993.1476 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV533 UT WOS:A1993LV53300019 PM 8371274 ER PT J AU LINDBLAD, P MCLAUGHLIN, JK MELLEMGAARD, A ADAMI, HO AF LINDBLAD, P MCLAUGHLIN, JK MELLEMGAARD, A ADAMI, HO TI RISK OF KIDNEY CANCER AMONG PATIENTS USING ANALGESICS AND DIURETICS - A POPULATION-BASED COHORT STUDY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RENAL-CELL CARCINOMA; HYPERTENSION; OBESITY AB The aim of this study was to determine the risk of kidney cancer in 2 cohorts defined on the basis of hospital discharge diagnoses associated with analgesic or diuretic use during the period 1965 to 1983. Patients were followed up through 1984 for cancer incidence. After excluding cancers in the first year of observation, 161 kidney cancers were observed vs. 138 expected among 54,662 patients in the analgesics cohort. The relative risk was higher for women than for men. When examined by sub-site within the kidney, risk for cancer of the renal pelvis was similar in magnitude to that for the renal parenchyma. Among 115,616 patients in the diuretics cohort, 278 kidney cancers occurred vs. 209 expected. The risk for women was higher than for men. This elevation in risk was confined to cancer of the renal parenchyma, with no significantly increased risk seen for cancer of the renal pelvis. Although we observed little excess risk among members of the analgesics cohort, the significantly elevated risk among patients using diuretics supports a number of recent studies, but inability to adjust for confounding factors such as obesity preclude drawing any conclusion regarding diuretics. Further research is warranted to assess in detail the relationship between diuretic use and cancer of the renal parenchyma. (C) 1993 Wiley-Liss, Inc. C1 UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,UPPSALA,SWEDEN. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. DANISH CANC SOC,DANISH CANC REGISTRY,COPENHAGEN,DENMARK. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP LINDBLAD, P (reprint author), SUNDSVALL HOSP,DEPT UROL,SUNDSVALL,SWEDEN. NR 20 TC 23 Z9 23 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 19 PY 1993 VL 55 IS 1 BP 5 EP 9 DI 10.1002/ijc.2910550103 PG 5 WC Oncology SC Oncology GA LT723 UT WOS:A1993LT72300002 PM 8344752 ER PT J AU LIEBMAN, JM BURBELO, PD YAMADA, Y FRIDMAN, R KLEINMAN, HK AF LIEBMAN, JM BURBELO, PD YAMADA, Y FRIDMAN, R KLEINMAN, HK TI ALTERED EXPRESSION OF BASEMENT-MEMBRANE COMPONENTS AND COLLAGENASES IN ASCITIC XENOGRAFTS OF OVCAR-3 OVARIAN-CANCER CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LAMININ RECEPTOR; MESSENGER-RNA; HUMAN-SKIN; CARCINOMA; RECOGNITION; MATRIGEL; HOMOLOGY; SEQUENCE; B1-CHAIN; B2-CHAIN AB Ascitic ovarian cancer cells, which derive from solid tumors, complicate the treatment of ovarian cancer by spreading throughout the peritoneal cavity. Because basement-membrane components may influence tumor-cell proliferation and dissemination, the present studies examined the production of (a) basement-membrane attachment and migration factors (laminin, fibronectin and type IV collagen); (b) a laminin receptor, the 32/67-kDa laminin-binding protein, the presence of which correlates with malignancy; and (c) metalloproteinases (types I and IV collagenase and stromelysin), by ascitic and cultured OVCAR-3 cells and solid OVCAR-3 tumors. The cultured cells and solid tumors produced high levels of mRNA encoding attachment factors and metalloproteinases, and low levels of mRNA for the 32/67-kDa laminin receptor. In contrast, the ascitic ovarian cells had low or undetectable levels of mRNA encoding laminin, type IV collagen and metalloproteinases, but higher levels of transcripts for the laminin receptor. Our results suggest that the apparent inability of ascitic OVCAR-3 cells to attach to host-tissue surfaces may be a consequence, in part, of low levels of expression of laminin, type IV collagen and/or type IV collagenase. (C) 1993 Wiley-Liss, Inc. C1 NIDR,BETHESDA,MD 20892. RP LIEBMAN, JM (reprint author), CIBA PHARMACEUT,DIV RES,556 MORRIS AVE,SUMMIT,NJ 07901, USA. RI Burbelo, Peter/B-1027-2009 NR 26 TC 25 Z9 25 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 19 PY 1993 VL 55 IS 1 BP 102 EP 109 DI 10.1002/ijc.2910550119 PG 8 WC Oncology SC Oncology GA LT723 UT WOS:A1993LT72300018 PM 8344742 ER PT J AU CARR, S AF CARR, S TI FETAL TISSUE SO NATURE LA English DT Letter RP CARR, S (reprint author), NIH,CTR SCI POLICY STUDIES,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 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 AUG 19 PY 1993 VL 364 IS 6439 BP 665 EP 665 DI 10.1038/364665e0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT677 UT WOS:A1993LT67700021 PM 8355776 ER PT J AU SLESAREV, AI STETTER, KO LAKE, JA GELLERT, M KRAH, R KOZYAVKIN, SA AF SLESAREV, AI STETTER, KO LAKE, JA GELLERT, M KRAH, R KOZYAVKIN, SA TI DNA TOPOISOMERASE-V IS A RELATIVE OF EUKARYOTIC TOPOISOMERASE-I FROM A HYPERTHERMOPHILIC PROKARYOTE SO NATURE LA English DT Article ID DESULFUROCOCCUS-AMYLOLYTICUS; METHANOPYRUS-KANDLERI; ARCHAEBACTERIA; 110-DEGREES-C; METHANOGENS; ARCHAEA; GENE AB THE DNA topoisomerases are ubiquitous enzymes that fulfil vital roles in the replication, transcription and recombination of DNA by carrying out DNA-strand passage reactions1-7. Here we characterize a prokaryotic counterpart to the eukaryotic topoisomerase I in the hyperthermophilic methanogen Methanopyrus kandleri8-10. The new enzyme, called topoisomerase V, has the following properties in common with eukaryotic topoisomerase I, which distinguish it from all other known prokaryotic topoisomerases: (1) its activity is Mg2+-independent; (2) it relaxes both negatively and positively supercoiled DNA; (3) it makes a covalent complex with the 3' end of the broken DNA strand; and (4) it is recognized by antibody raised against human topoisomerase I. Eukaryotic-like enzymes have been discovered in some hyperthermophilic prokaryotes, namely the eocytes11 and the extremely thermophilic archaebacteria12, and hyperthermophilic homologues of eukaryotic DNA polymerase-a, transcription factor IIB and DNA ligase13-15 have all been reported. Thus our findings support the idea that some essential parts of the eukaryotic transcription-translation and replication machineries were in place before the emergence of eukaryotes, and that the closest living relatives of eukaryotes may be hyperthermophiles. C1 RUSSIAN ACAD SCI,INST MOLEC GENET,MOSCOW 123182,RUSSIA. UKRAINIAN ACAD SCI,RE KAVETSKY INST ONCOL & RADIOBIOL,KIEV 252127,UKRAINE. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. UNIV REGENSBURG,LEHRSTUHL MIKROBIOL,W-8400 REGENSBURG,GERMANY. NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SLESAREV, AI (reprint author), UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024, USA. NR 21 TC 67 Z9 69 U1 1 U2 11 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 19 PY 1993 VL 364 IS 6439 BP 735 EP 736 DI 10.1038/364735a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT677 UT WOS:A1993LT67700064 PM 8395022 ER PT J AU LONGO, DL DEVITA, VT YOUNG, RC AF LONGO, DL DEVITA, VT YOUNG, RC TI CHOP VERSUS INTENSIVE REGIMENS IN NON-HODGKINS-LYMPHOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID MOPP C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP LONGO, DL (reprint author), NCI,FREDERICK,MD 21702, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 19 PY 1993 VL 329 IS 8 BP 580 EP 581 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LR892 UT WOS:A1993LR89200020 PM 7687747 ER PT J AU RADER, DJ BREWER, HB AF RADER, DJ BREWER, HB TI ABETALIPOPROTEINEMIA - NEW INSIGHTS INTO LIPOPROTEIN ASSEMBLY AND VITAMIN-E METABOLISM FROM A RARE GENETIC-DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID APOLIPOPROTEIN-B GENE; TRIGLYCERIDE-TRANSFER PROTEIN; NORMOTRIGLYCERIDEMIC ABETALIPOPROTEINEMIA; E-DEFICIENCY; 2 FAMILIES; TOCOPHEROL; ABSENCE; MALABSORPTION; EXCLUSION RP RADER, DJ (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 81 Z9 83 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 18 PY 1993 VL 270 IS 7 BP 865 EP 869 DI 10.1001/jama.270.7.865 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LR612 UT WOS:A1993LR61200034 PM 8340987 ER PT J AU FENTON, RG TAUB, DD KWAK, LW SMITH, MR LONGO, DL AF FENTON, RG TAUB, DD KWAK, LW SMITH, MR LONGO, DL TI CYTOTOXIC T-CELL RESPONSE AND IN-VIVO PROTECTION AGAINST TUMOR-CELLS HARBORING ACTIVATED RAS PROTOONCOGENES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TOXIC LYMPHOCYTES-T; CLASS-I; IMMUNE-RESPONSES; SOLUBLE-PROTEIN; ACCESSORY CELLS; DENDRITIC CELLS; ANTIGEN; INDUCTION; MICE; IMMUNIZATION AB Background: Activated forms of the ras proto-oncogene have been found in approximately 30% of human malignancies, including pancreatic, colon, and lung adenocarcinomas. Ras oncoproteins arise by somatic mutation and contain amino acid changes at residues 12, 13, or 61, thus generating unique tumor-specific proteins that are attractive targets for cancer therapy. Purpose: The goal of this study was to determine whether vaccination with mutant Ras protein could lead to the generation of cytotoxic T lymphocytes (CTLs) specific for the mutant epitope and to protection against challenge with tumor cells expressing the mutant oncoprotein. Methods: To determine a methodology for generating CTL responses following immunization with soluble protein, ovalbumin was used as a model tumor antigen. C57BL/6 mice were immunized with soluble ovalbumin administered intraperitoneally at 2-week intervals or with intravenous injection of ovalbumin or osmotically loaded splenocytes. Immunized mice were challenged with E.G7 cells (which express a transfected ovalbumin gene), and tumor growth was monitored. Generation of ovalbumin-specific CTLs was determined by Cr-51 release assays. Purified wild-type or mutant H-Ras proteins (containing single amino acid substitutions at position 12 converting Gly to Arg or Val) were used to immunize BALB/c mice intraperitoneally. Ras-immunized mice were challenged with tumor cells containing Arg 12 or Val 12 mutations or not harboring mutant forms of Ras. Cytolytic and proliferative, responses to mutant forms of Ras were studied, and the effects of in vivo depletion of CD4+ or CD8+ T lymphocytes were determined. Results: In vivo challenge with E.G7 showed that intraperitoneal immunization with soluble ovalbumin was as effective as osmotic loading, resulting in long-term disease-free survival of some mice and the development of ovalbumin-specific CTLs. Immunization with Arg 12 Ras led to with tumor cells containing an Arg 12 mutation, while no protection was afforded against tumors expressing other forms of Ras or other oncogenes. Splenocytes from BALB/c mice immunized with Arg 12 Ras demonstrated cytolytic activity specific against tumor cells expressing Arg 12 Ras, with most of this activity residing in the CD8+ subset. Mutation-specific proliferation to Arg 12 Ras peptides was also observed. Immunization with Val 12 Ras did not elicit detectable Val 12-specific immunity. Conclusions: Antigen-specific CTLs can be induced following intraperitoneal immunization of mice with purified, soluble proteins. For both ovalbumin and Arg 12 Ras, specific in vivo protection against tumor cell challenge was observed. C1 NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. RP FENTON, RG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 39 TC 76 Z9 76 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 AUG 18 PY 1993 VL 85 IS 16 BP 1294 EP 1302 DI 10.1093/jnci/85.16.1294 PG 9 WC Oncology SC Oncology GA LR766 UT WOS:A1993LR76600014 PM 8340941 ER PT J AU DEGTYAREV, MY SPIEGEL, AM JONES, TLZ AF DEGTYAREV, MY SPIEGEL, AM JONES, TLZ TI THE G-PROTEIN ALPHA(S)-SUBUNIT INCORPORATES [H-3] PALMITIC ACID AND MUTATION OF CYSTEINE-3 PREVENTS THIS MODIFICATION SO BIOCHEMISTRY LA English DT Note ID BINDING REGULATORY PROTEINS; ALPHA-SUBUNIT; MEMBRANE ATTACHMENT; SIGNAL TRANSDUCTION; BETA-GAMMA; COS CELLS; MYRISTOYLATION; RECEPTOR; PALMITOYLATION; ASSOCIATION AB We investigated whether alpha(s) could be acylated by palmitate by transfecting COS cells with the cDNA for the wild-type, long form of alpha(s) and metabolically labeling with [H-3]palmitate or [S-35]methionine. Cells were separated into particulate and soluble fractions and immunoprecipitated with a specific peptide antibody. [H-3]Palmitate was incorporated into both endogenous and transfected alpha(s). Inhibition of protein synthesis with cycloheximide did not block the radiolabeling of alpha(s) with [H-3]palmitate. Hydroxylamine treatment caused a release of the tritium radiolabel, demonstrating that the incorporation was through a thioester bond. The tritium radiolabel was base-labile and comigrated with [H-3]palmitate on thin-layer chromatography. The third residue of the wild-type alpha(s) was mutated from a cysteine to an alanine by site-directed mutagenesis. This mutant was expressed in COS cells and localized to the particulate fraction as determined by immunoprecipitation of the [S-35]methionine-labeled cells. The cysteine-3 mutant did not undergo radiolabeling with [H-3]palmitate, indicating that this residue is crucial for the modification. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C-101,BETHESDA,MD 20892. NR 29 TC 97 Z9 98 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 17 PY 1993 VL 32 IS 32 BP 8057 EP 8061 DI 10.1021/bi00083a001 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV969 UT WOS:A1993LV96900001 PM 8347607 ER PT J AU DAVID, C FISHBURN, CS MONSMA, FJ SIBLEY, DR FUCHS, S AF DAVID, C FISHBURN, CS MONSMA, FJ SIBLEY, DR FUCHS, S TI SYNTHESIS AND PROCESSING OF D2-DOPAMINE RECEPTORS SO BIOCHEMISTRY LA English DT Article ID D2 DOPAMINE RECEPTOR; ANTIPEPTIDE ANTIBODIES; MOLECULAR-BIOLOGY; RAT; BINDING; CLONING; IDENTIFICATION; PALMITOYLATION; FORM; D3 AB Dopamine receptors belong to a superfamily of neurotransmitter receptors that are functionally coupled to guanine nucleotide binding proteins. In this study, we have used Chinese hamster ovary (CHO) cells stably transfected with the rat D2L receptor, in conjunction with specific anti-peptide antibodies that we have developed, in order to visualize this protein and the course of its synthesis. The newly synthesized receptor exists as a 45-kDa protein which undergoes further processing to a 75-kDa glycosylated receptor in the CHO cells. In pulse-chase experiments it was noticed that a 35-kDa precursor was present which disappeared after 30 min. In order to determine whether this 35-kDa protein represents an unprocessed form of the receptor, we have employed an in vitro translation system with cDNA constructs coding for both the murine D2 and D3 dopamine receptor isoforms. In the absence of processing, the D2 and D3 receptors have an apparent molecular mass of 35 kDa. The translated proteins were shown to be the full length receptors by immunoprecipitation with various anti-peptide antibodies and by the demonstration that they can undergo glycosylation to apparent molecular masses of approximately 45 kDa in an in vitro system. C1 WEIZMANN INST SCI,DEPT BIOQUIM MACROMOLEC,IL-76100 REHOVOT,ISRAEL. NIH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NR 29 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 17 PY 1993 VL 32 IS 32 BP 8179 EP 8183 DI 10.1021/bi00083a018 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV969 UT WOS:A1993LV96900018 PM 8347618 ER PT J AU YOO, SH AF YOO, SH TI PH-DEPENDENT ASSOCIATION OF CHROMOGRANIN-A WITH SECRETORY VESICLE MEMBRANE AND A PUTATIVE MEMBRANE-BINDING REGION OF CHROMOGRANIN-A SO BIOCHEMISTRY LA English DT Article ID ADRENAL CHROMAFFIN GRANULES; MUSCLE SARCOPLASMIC-RETICULUM; AMINO-ACID SEQUENCE; MESSENGER-RNA; CONFORMATIONAL CHANGE; MOLECULAR-CLONING; NERVOUS-TISSUE; PROTEIN; CALSEQUESTRIN; CALRETICULIN AB Chromogranin A is a low-affinity, high-capacity Ca2+ binding protein, postulated to be responsible for the Ca2+ buffering role of secretory vesicles, and has been found only in the soluble portions of the vesicular proteins. Contrary to the generally accepted notion of chromogranin A existing as a soluble matrix protein, chromogranin A bound to the secretory vesicle membrane at the intravesicular pH of 5.5 and freed from the membrane when the pH was raised to a more physiological pH of 7.5. Trypsin digestion studies of the vesicle membrane suggested that chromogranin A interacts with the protein component(s) on the intravesicular side of the membrane. Furthermore, in a study using 14 synthetic chromogranin A peptides which represent various portions of chromogranin A, a segment in the N-terminal region (residues 18-37) was shown to bind to the vesicle membrane in a pH-dependent manner. The pH-dependent vesicle membrane binding property of chromogranin A appears to be of fundamental physiological importance with regard to the potential roles of chromogranin A in secretory vesicle biogenesis, particularly in segregating secretory vesicle membranes from others in the trans-Golgi network, and also in transmitting extravesicular signals such as inositol 1,4,5-trisphosphate or inositol 1,3,4,5-tetrakisphosphate for Ca2+ release or uptake to the inside of vesicles. RP YOO, SH (reprint author), NIDCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-15,BETHESDA,MD 20892, USA. NR 48 TC 54 Z9 54 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 17 PY 1993 VL 32 IS 32 BP 8213 EP 8219 DI 10.1021/bi00083a023 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV969 UT WOS:A1993LV96900023 PM 8347621 ER PT J AU VINCENT, JS REVAK, SD COCHRANE, CD LEVIN, IW AF VINCENT, JS REVAK, SD COCHRANE, CD LEVIN, IW TI INTERACTIONS OF MODEL HUMAN PULMONARY SURFACTANTS WITH A MIXED PHOSPHOLIPID-BILAYER ASSEMBLY - RAMAN-SPECTROSCOPIC STUDIES SO BIOCHEMISTRY LA English DT Article ID PROTEIN SP-B; NEGATIVELY CHARGED PHOSPHOLIPIDS; DEUTERATED PHOSPHOLIPIDS; MEMBRANE-STRUCTURE; PHOSPHATIDYLGLYCEROL BILAYERS; PACKING CHARACTERISTICS; SPECTRAL PARAMETERS; PHASE-TRANSITIONS; CRYSTAL-STRUCTURE; LIPIDS AB The temperature dependence and acyl chain packing properties of the binary lipid mixtures of dipalmitoylphosphatidylcholine-d62 (DPPC-d62)/dipalmitoylphosphatidylglycerol (DPPG) multilayers, reconstituted with two synthetic peptides for modeling the membrane behavior of the SP-B protein associated with human pulmonary surfactant, were investigated by vibrational Raman spectroscopy. The synthetic peptides consisted of 21 amino acid residues representing repeating charged units of either lysine or aspartic acid separated by hydrophobic domains consisting of four leucines (KL4 or DL4, respectively). These peptides were designed to mimic the alternating hydrophobic and hydrophilic sequences defining the low molecular weight SP-B protein. Raman spectroscopic parameters consisting of integrated band intensities, line widths, and relative peak height intensity ratios were used to probe the bilayer order/disorder characteristics of the liposomal perturbations reflected by the reconstituted membrane assemblies. Temperature profiles derived from the various Raman intensity parameters for the 3100-2800-cm-1 carbon-hydrogen (C-H) and the 2000-2300-cm-1 carbon-deuterium (C-D) stretching mode regions, spectral intervals representative of acyl chain vibrations, reflected lipid reorganizations specific to peptide interactions with either the DPPC-d62 or DPPG component of the liposome. For the multilamellar surfactant systems composed of either KL4 Or DL4 reconstituted with the binary DPPG/DPPC-d62 lipid mixture, the breadth of the gel to liquid crystalline phase transition temperatures T(M), defined by acyl chain C-H and C-D stretching mode order/disorder parameters, increased from about 1-degrees-C in the peptide-free systems to over 10-degrees-C. This breadth in T(M) indicates an increased lipid disorder and a distinct noncooperative chain melting process for the model liposomes. In comparing the interactions of the synthetic peptides with DPPG/DPPC mixtures and with DPPC liposomes alone, the negatively charged DL4 peptide perturbs the DPPG component of the lipid mixture more strongly than the DPPC-d62 component; moreover, the DL4 peptide disrupts the structure of the DPPG lipid domains in the binary mixture to a greater extent than the KL4 peptide. The microdomain heterogeneity of the binary lipid mixture arising from lipid-peptide interactions is discussed in terms of the Raman spectral properties of the multilayers. The Raman data in conjunction with previous bubble surfactometer and animal studies (Cochrane & Revak, 1991) suggest that lipid domain structures are present in functional surfactants and that the dynamic bilayer microheterogeneity induced by the surfactant peptide or protein is essential for pulmonary mechanics. C1 UNIV MARYLAND, DEPT CHEM, 5401 WILKENS AVE, CATONSVILLE, MD 21228 USA. Scripps Res Inst, RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NIDDKD, CHEM PHYS LAB, BETHESDA, MD 20892 USA. NR 39 TC 32 Z9 32 U1 4 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 17 PY 1993 VL 32 IS 32 BP 8228 EP 8238 DI 10.1021/bi00083a025 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV969 UT WOS:A1993LV96900025 PM 8347622 ER PT J AU COZZI, PJ PADRID, PA TAKEDA, J ALEGRE, ML YUHKI, N LEFF, AR AF COZZI, PJ PADRID, PA TAKEDA, J ALEGRE, ML YUHKI, N LEFF, AR TI SEQUENCE AND FUNCTIONAL-CHARACTERIZATION OF FELINE INTERLEUKIN-2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IMMUNODEFICIENCY VIRUS; LEUKEMIA-VIRUS; CATS; CDNA; EXPRESSION; INFECTIONS; GROWTH; CELLS; RNA C1 UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP COZZI, PJ (reprint author), UNIV CHICAGO,DEPT MED,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. FU NHLBI NIH HHS [NHLBI HL-08653, NHLBI HL-32495, NHLBI HL-46368] NR 21 TC 10 Z9 13 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 AUG 16 PY 1993 VL 194 IS 3 BP 1038 EP 1043 DI 10.1006/bbrc.1993.1926 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT517 UT WOS:A1993LT51700009 PM 8352761 ER PT J AU KOMATSU, K OEDA, T STROTT, CA AF KOMATSU, K OEDA, T STROTT, CA TI CLONING AND SEQUENCE-ANALYSIS OF THE 5'-FLANKING REGION OF THE ESTROGEN SULFOTRANSFERASE GENE - STEROID-RESPONSE ELEMENTS AND CELL-SPECIFIC NUCLEAR DNA-BINDING PROTEINS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXPRESSION C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,ADRENAL CELL BIOL SECT,BETHESDA,MD 20892. NR 14 TC 16 Z9 16 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 AUG 16 PY 1993 VL 194 IS 3 BP 1297 EP 1304 DI 10.1006/bbrc.1993.1965 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT517 UT WOS:A1993LT51700048 PM 8352788 ER PT J AU OSAWA, Y DAVILA, JC AF OSAWA, Y DAVILA, JC TI PHENCYCLIDINE, A PSYCHOTOMIMETIC AGENT AND DRUG OF ABUSE, IS A SUICIDE INHIBITOR OF BRAIN NITRIC-OXIDE SYNTHASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COVALENT BINDING; RABBIT LIVER; IMINIUM ION; L-ARGININE; INACTIVATION; METABOLISM; INVITRO RP OSAWA, Y (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 18 TC 27 Z9 28 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 AUG 16 PY 1993 VL 194 IS 3 BP 1435 EP 1439 DI 10.1006/bbrc.1993.1985 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT517 UT WOS:A1993LT51700068 PM 7688965 ER PT J AU MILLER, M RAO, JKM WLODAWER, A GRIBSKOV, MR AF MILLER, M RAO, JKM WLODAWER, A GRIBSKOV, MR TI A LEFT-HANDED CROSSOVER INVOLVED IN AMIDOHYDROLASE CATALYSIS - CRYSTAL-STRUCTURE OF ERWINIA-CHRYSANTHEMI L-ASPARAGINASE WITH BOUND L-ASPARTATE SO FEBS LETTERS LA English DT Article DE L-ASPARAGINASE; LEFT-HANDED CROSSOVER; CRYSTAL STRUCTURE; L-ASPARTATE-BOUND AMIDOHYDROLASE; THREONINE AS NUCLEOPHILE; ERWINIA-CHRYSANTHEMI ID ESCHERICHIA-COLI; BINDING PROTEIN; SITE; DEHYDROGENASE; RESOLUTION; SUBTILISIN; MECHANISM; PEPTIDE AB The crystal structure of L-asparaginase from Erwinia chrysanthemi in the presence and absence Of L-aspartate was determined at 1.8 angstrom resolution. Conserved residues in a left-handed crossover (a rare occurrence in protein structures) link pairs of dimers into the catalytically active tetrameric form of the enzyme. The structure of ErA containing bound aspartic acid shows that this unusual strand connectivity is an essential part of the active site architecture, responsible for releasing the product of the enzymatic hydrolysis. The orientation of the bound aspartate indicates for the first time a threonine residue as a catalytic nucleophile. RP MILLER, M (reprint author), NCI,FCRDC,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. RI Miller, Maria/I-1636-2013; OI Miller, Maria/0000-0003-0252-5348; Gribskov, Michael/0000-0002-1718-0242 FU NCI NIH HHS [N01-CO-74101] NR 23 TC 52 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 16 PY 1993 VL 328 IS 3 BP 275 EP 279 DI 10.1016/0014-5793(93)80943-O PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LT635 UT WOS:A1993LT63500013 PM 8348975 ER PT J AU BARBER, AM ZHURKIN, VB ADHYA, S AF BARBER, AM ZHURKIN, VB ADHYA, S TI CRP-BINDING SITES - EVIDENCE FOR 2 STRUCTURAL CLASSES WITH 6-BP AND 8-BP SPACERS SO GENE LA English DT Article DE DNA-BINDING PROTEINS; A-DNA; RECOMBINANT DNA; LAC OPERON ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; GENE ACTIVATOR PROTEIN; ESCHERICHIA-COLI; B-DNA; ANISOTROPIC FLEXIBILITY; BASE SEQUENCE; CAP PROTEIN; REPRESSOR; OPERATOR; SPECIFICITY AB While classifying protein binding DNA sequences of the type GTGN(x)CAC, based on the size of N(x) [Shumilov, Mol. Biologya (Engl. Transl.) 21 (1987) 168-187], we had previously found that the cyclic AMP receptor protein (CRP)-binding sites found in the Escherichia coli genome are of at least two classes: (i) those with a conventional 6-bp spacer (N6) and (ii) those with a potential 8-bp spacer (N8) [Barber and Zhurkin, J. Biomol. Struct. Dyn. 8 (1990) 213-232]. In this paper, we present the first experimental evidence that CRP binds to DNA with an N8 spacer with relatively high affinity, as measured by gel electrophoresis of CRP-DNA complexes. We have tested two types of N8 spacers: A+T-rich and G+C-rich. Compared with the affinity of CRP for a reference site with an N6 spacer, the binding strength of CRP toward an A+T-rich N8 sequence is lower and that toward a G + C-rich N8 site is comparable. Just like DNA sites with N6 spacers, those with N8 spacers utilize both halves of the symmetrical protein recognition sequences, TGTGA and TCACA. Because of the increased number of nucleotides in the N8 spacer, the two recognition sequences in DNA will have an increased distance and a helical twist between them. These would cause displacement of the two recognition sequences with respect to the two symmetrically located alpha-helices of the CRP dimer, if there is no change in the DNA conformation. To explain the proper alignment of the recognition elements in DNA and CRP, we propose that the orientation of the two recognition elements in DNA is restored to the original orientation as in the N6 spacer, and the physical distance in DNA between the recognition sequences is decreased. The mechanism of such changes conceivably depends on the nature of the N8 sequence. A+T-rich N, sequences supposedly unwind in the center to realign the angular orientation of the two recognition sequences and bend into the minor groove facing the protein to reduce the distance, whereas for the G+C-rich N8 sequences, a transition from B- to A-DNA would bring about the required unwinding and compression. C1 NCI,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BLDG 37,ROOM 2E 16,BETHESDA,MD 20892. NCI,MATH BIOL LAB,BETHESDA,MD 20892. ENGELHARDT INST MOLEC BIOL,MOSCOW,RUSSIA. NR 50 TC 21 Z9 21 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 AUG 16 PY 1993 VL 130 IS 1 BP 1 EP 8 DI 10.1016/0378-1119(93)90339-5 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LT636 UT WOS:A1993LT63600001 PM 8393822 ER PT J AU LEWIS, DJ LUCK, RL SILVERTON, JV AF LEWIS, DJ LUCK, RL SILVERTON, JV TI STRUCTURE OF BIS[CIS-1,2-BIS(DIPHENYLPHOSPHINO)ETHYLENE]DICHLORORHENIUM(II) HEXANE SOLVATE SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Note AB [ReCl2(C26H22P2)2].C6H14 (I), M(r) = 1136.11, monoclinic, P2(1)/c, a = 11.426 (2), b = 13.078 (2), c = 17.323 (3) angstrom, beta = 95.27 (1)-degrees, V = 2577.7 (6) angstrom3, Z = 2, D(x) = 1.46 g cm-3, lambda(Mo Kalpha) = 0.71073 angstrom, mu = 26.5 cm-1, F(000) = 1150, T = 296 K, R = 0.034 for 3269 [F(o)2 > 3sigma(F(o)2)] reflections. The Re atom in (I) is located on an inversion point, fixed at the origin. One Cl and a complete tertiary phosphine ligand (Ph2PCHCHPPh2) are situated around the Re atom so as to generate a pseudo-octahedral geometry with a P1-Re-P2 angle of 79.07 (5)-degrees and P1-Re-P2' angle of 100.93 (5)-degrees. The Re-Cl, Re-P1 and Re-P2 distances are 2.432 (2), 2.401 (2) and 2.398 (2) angstrom, respectively. Bond distances [GRAPHICS] and angles for the phenyl rings range from 1.34 (1) to 1.41 (1) angstrom and 117.4 (6) to 122.0 (7)-degrees with averages of 1.38 (1) angstrom and 120.0 (1)-degrees, respectively. C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 4 TC 3 Z9 4 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD AUG 15 PY 1993 VL 49 BP 1424 EP 1426 DI 10.1107/S0108270193099780 PN 8 PG 3 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA LY133 UT WOS:A1993LY13300004 PM 8217013 ER PT J AU SHIRANI, J MARON, BJ CANNON, RO SHAHIN, S ROBERTS, WC AF SHIRANI, J MARON, BJ CANNON, RO SHAHIN, S ROBERTS, WC TI CLINICOPATHOLOGICAL FEATURES OF HYPERTROPHIC CARDIOMYOPATHY MANAGED BY CARDIAC TRANSPLANTATION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; DILATED CARDIOMYOPATHY; PROGRESSION; HEART AB Clinical records, electrocardiographic, echocardiographic, hemodynamic and radionuclide data, and the operatively excised hearts were reviewed in 10 Patients (aged 19 to 46 years, mean 35) who had cardiac transplantation for hypertrophic cardiomyopathy. Severe congestive heart failure unassociated with outflow obstruction was the indication for transplantation in 9 patients. During a pretransplantation period ranging from 45 to 312 months (mean 137) in these 9 patients, pulmonary artery wedge pressure increased from 19 +/- 9 to 27 +/- 7 mm Hg, left ventricular ejection fraction decreased from 51 +/- 11% to 41 +/- 1%, left ventricular end-diastolic dimension increased from 42 +/- 6 to 48 +/- 4 mm, and total 12-lead QRS voltage decreased from 209 +/- 50 to 156 +/- 41 mm. In these 9 patients, the explanted hearts had dilated left ventricular cavities, and 8 had left ventricular scars without significant narrowing of the epicardial coronary arteries. The tenth patient had a nondilated left ventricular cavity and had transplantation because of recurrent, refractory syncope. Of the 10 patients, 3 died within the first month, and another died 8 months after transplantation. The remaining 6 patients have survived 20 to 54 months (mean 39) after transplantation and are in functional class I or II. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 9 TC 47 Z9 47 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1993 VL 72 IS 5 BP 434 EP 440 DI 10.1016/0002-9149(93)91136-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LT361 UT WOS:A1993LT36100012 PM 8352187 ER PT J AU DOMANSKI, MJ SAKSENA, S AF DOMANSKI, MJ SAKSENA, S TI EVALUATION OF TREATMENT STRATEGIES OF MALIGNANT VENTRICULAR TACHYARRHYTHMIAS IN THE ERA OF THE IMPLANTABLE DEFIBRILLATOR SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID HOSPITAL CARDIAC-ARREST; CARDIOVERTER DEFIBRILLATOR; SURVIVAL; FIBRILLATION; TACHYCARDIA; DETERMINANTS; ARRHYTHMIAS; DEATH C1 UNIV MED & DENT NEW JERSEY, NEWARK, NJ 07103 USA. RP DOMANSKI, MJ (reprint author), NHLBI, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1993 VL 72 IS 5 BP 455 EP 457 DI 10.1016/0002-9149(93)91140-D PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LT361 UT WOS:A1993LT36100016 PM 8352189 ER PT J AU ARMENIAN, HK HOOVER, DR RUBB, S METZ, S KASLOW, R VISSCHER, B CHMIEL, J KINGSLEY, L SAAH, A AF ARMENIAN, HK HOOVER, DR RUBB, S METZ, S KASLOW, R VISSCHER, B CHMIEL, J KINGSLEY, L SAAH, A TI COMPOSITE RISK SCORE FOR KAPOSI-SARCOMA BASED ON A CASE-CONTROL AND LONGITUDINAL-STUDY IN THE MULTICENTER AIDS COHORT STUDY (MACS) POPULATION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; INFECTION; RISK FACTORS; SARCOMA, KAPOSI ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL MEN; EPIDEMIOLOGY; TYPE-1; INFECTION AB The possibility that an agent in addition to human immunodeficiency virus type 1 may be involved in the etiology of Kaposi's sarcoma in acquired immunodeficiency syndrome (AIDS) patients was investigated between 1984 and 1992 in this nested case-control analysis from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men. A total of 316 cases of Kaposi's sarcoma were identified and compared with 51 0 participants with AIDS and no evidence of cancer. More of the Kaposi's sarcoma cases were from Los Angeles and used a higher number of recreational drugs. The Kaposi's sarcoma cases were also more active sexually. There was a dose-response relation between Kaposi's sarcoma and the number of sexual partners, with an odds ratio of 2 between the most and least sexually active subgroups. The odds ratio for Kaposi's sarcoma increased to 4.18 (95% confidence interval 1.29-14.1) in the presence of a history of five infections. Hepatitis and gonorrhea contributed the most to this relation. The various observed odds ratios did not change after multivariate adjustment for the other risk factors. A model was developed combining all predictive associations into a composite risk score ranging from one to 12 and based on history of infections, sexual activity, use of poppers/nitrites, and having had sexual partners from the West Coast of the United States. The subgroup with the highest scores, compared to the subgroup with the lowest score, had an odds ratio of 8.93 (95% confidence interval 3.21-30.44) for Kaposi's sarcoma. A longitudinal proportional hazards analysis among all 2,190 human immunodeficiency virus type 1-seroprevalent men at study entry, based on this risk score and CD4 cells at baseline, confirmed these findings. Identifying these specific subgroups that are at high and low risk for Kaposi's sarcoma will help future investigations to be more focused in their search for an additional etiologic factor for Kaposi's sarcoma in AIDS. C1 NIH, EPIDEMIOL & BIOMETRY BRANCH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, DEPT EPIDEMIOL, LOS ANGELES, CA USA. NORTHWESTERN UNIV, SCH MED, CTR CANC, BIOMETRY SECT, CHICAGO, IL 60611 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT INFECT DIS & MICROBIOL, PITTSBURGH, PA 15260 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT EPIDEMIOL, PITTSBURGH, PA 15260 USA. RP ARMENIAN, HK (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD 21218 USA. FU NIAID NIH HHS [N01-AI-32535, N01-AI-72676, N01-AI-72634] NR 24 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1993 VL 138 IS 4 BP 256 EP 265 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LZ156 UT WOS:A1993LZ15600006 PM 8356966 ER PT J AU HOOVER, DR BLACK, C JACOBSON, LP MARTINEZMAZA, O SEMINARA, D SAAH, A VONROENN, J ANDERSON, R ARMENIAN, HK AF HOOVER, DR BLACK, C JACOBSON, LP MARTINEZMAZA, O SEMINARA, D SAAH, A VONROENN, J ANDERSON, R ARMENIAN, HK TI EPIDEMIOLOGIC ANALYSIS OF KAPOSI-SARCOMA AS AN EARLY AND LATER AIDS OUTCOME IN HOMOSEXUAL MEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; CYTOKINES; RISK; RISK FACTORS; SARCOMA, KAPOSI; SEXUALLY TRANSMITTED DISEASES; SMOKING ID HUMAN-IMMUNODEFICIENCY-VIRUS; CIGARETTE-SMOKING; ALVEOLAR MACROPHAGES; HIV-INFECTION; ONCOSTATIN-M; CELLS; INTERLEUKIN-6; COHORT; EXPERIENCE; COFACTORS AB The authors separately studied the epidemiology (risk and risk factors) of Kaposi's sarcoma occurring as an initial acquired immunodeficiency syndrome (AIDS) outcome (early Kaposi's sarcoma) and later after a different initial AIDS outcome (later Kaposi's sarcoma) in a cohort of 2,591 human immunodeficiency virus type 1-infected gay men of the Multicenter Al DS Cohort Study between 1984 and 1992. Among 844 AIDS cases, 202 presented with early Kaposi's sarcoma, 101 subsequently developed later Kaposi's sarcoma, and 541 were not diagnosed with Kaposi's sarcoma. Overall, 37.4% of AIDS cases were diagnosed with Kaposi's sarcoma prior to death. Kaposi's sarcoma diagnosed on the skin was significantly more common with early Kaposi's sarcoma (77.3%) than with later Kaposi's sarcoma (65.1%). Men presenting with an AIDS outcome other than Kaposi's sarcoma were at high risk for later Kaposi's sarcoma. Later Kaposi's sarcoma onset in men with a previous AIDS outcome was associated with the following characteristics: 1) lower immune status prior to AIDS and 2) longer post-AIDS survival. A Kaposi's sarcoma diagnosis in a man with a previous AIDS illness approximately doubled the risk (hazard) for death. Histories of urethral gonorrhea and scabies prior to study entry were more common in early Kaposi's sarcoma cases than in later Kaposi's sarcoma cases. However, self-reported sexual activity at study entry and prior to AIDS onset was highest in the later Kaposi's sarcoma group. In this cohort, cigarette smoking had a protective association against all Kaposi's sarcoma in univariate and multivariate models. Only 21.0% of the later Kaposi's sarcoma and 25.0% of the early Kaposi's sarcoma men smoked at least one-half pack of cigarettes daily at study entry compared with 33.8% of non-Kaposi's sarcoma and 35.5% of seroprevalent men still AIDS free. The reasons for this surprising association are unclear. However, other evidence which documents that habitual smoking alters the immune system (and possibly cytokine levels) in ways that could perhaps influence Kaposi's sarcoma pathogenesis should be considered. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. NCI,BETHESDA,MD 20892. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. RP HOOVER, DR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,ROOM 784,624 N BROADWAY,BALTIMORE,MD 21205, USA. RI Martinez-Maza, Otoniel/B-2667-2009 OI Martinez-Maza, Otoniel/0000-0003-1364-0675 FU NIAID NIH HHS [N01-AI-32535, N01-AI-72634, N01-AI-72676] NR 33 TC 72 Z9 73 U1 1 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 AUG 15 PY 1993 VL 138 IS 4 BP 266 EP 278 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LZ156 UT WOS:A1993LZ15600007 PM 8356967 ER PT J AU AGBARIA, R FORD, H KELLEY, JA XIE, FM POLITI, P GREM, JL COONEY, DA MARQUEZ, VE ALLEGRA, CJ JOHNS, DG AF AGBARIA, R FORD, H KELLEY, JA XIE, FM POLITI, P GREM, JL COONEY, DA MARQUEZ, VE ALLEGRA, CJ JOHNS, DG TI MEASUREMENT OF CYCLOPENTENYL CYTOSINE 5'-TRIPHOSPHATE IN-VITRO AND IN-VIVO BY MULTIDIMENSIONAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ANTITUMOR C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. RP AGBARIA, R (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37-5B22,BETHESDA,MD 20892, USA. NR 13 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 1993 VL 213 IS 1 BP 90 EP 96 DI 10.1006/abio.1993.1390 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LR462 UT WOS:A1993LR46200015 PM 8238887 ER PT J AU WANNER, C RADER, D BARTENS, W KRAMER, J BREWER, HB SCHOLLMEYER, P WIELAND, H AF WANNER, C RADER, D BARTENS, W KRAMER, J BREWER, HB SCHOLLMEYER, P WIELAND, H TI ELEVATED PLASMA LIPOPROTEIN(A) IN PATIENTS WITH THE NEPHROTIC SYNDROME SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE NEPHROTIC SYNDROME; LIPOPROTEIN-(A); CORONARY ARTERIOSCLEROSIS; APOLIPOPROTEIN-A; THROMBOSIS ID LP(A) GLYCOPROTEIN PHENOTYPES; CARDIOVASCULAR-DISEASE; SIZE HETEROGENEITY; GLYCEMIC CONTROL; RISK FACTOR; APOLIPOPROTEIN(A); SERUM; ATHEROSCLEROSIS; TRANSPLANTATION; HEMODIALYSIS AB Objective: To examine the influence of the nephrotic syndrome on lipoprotein(a) [Lp(a)], a plasma lipoprotein associated with atherosclerotic cardiovascular disease independently of low-density lipoproteins. Factors that modulate plasma Lp(a) concentrations are poorly understood. Patients: A total of 62 patients: 47 with primary kidney disease and 15 with diabetic nephropathy. Measurements: Lipoprotein(a) levels were determined by enzyme-linked immunosorbent assay. Because apo(a) phenotype has a significant effect on Lp(a) levels, apo(a) isoforms were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoblotting; the data were compared with a healthy control group. Results: Nephrotic patients had significantly higher Lp(a) levels (mean, +/- SE, 69 +/- 10 mg/dL; median, 46 mg/dL, <0.01) compared with 91 healthy controls (mean, 18 +/- 2 mg/dL; median 9 mg/dL). Sixty percent of the patients and 18% of the controls had values greater than 30 mg/dL. Lipoprotein(a) levels correlated significantly with apolipoprotein B, serum cholesterol, and low-density lipoprotein cholesterol but showed no correlation with creatinine, albumin, or proteinuria. Within all apo(a) isoform classes, higher concentrations of Lp(a) were seen in the nephrotic patients compared with controls (P < 0.05). Finally, in nine patients with primary kidney disease and elevated Lp(a) levels, remission of the nephrotic syndrome was induced using immunosuppressive drugs and Lp(a) values decreased dramatically (pretreatment mean, 90 +/- 15 mg/dL versus remission mean, 31 +/- 8 mg/dL). A decrease in Lp(a) levels was also observed when patients with diabetic nephropathy progressed to end-stage renal disease (nephropathy mean, 56 +/- 11 mg/dL versus dialysis mean, 34 +/- 4 10 mg/dL; n = 7). Conclusions. Most patients with the nephrotic syndrome have Lp(a) concentrations that are substantially elevated compared with controls of the same apo(a) isoform. Because Lp(a) concentrations are substantially reduced when remission of the nephrotic syndrome is induced, it is likely that the nephrotic syndrome results directly in elevation of Lp(a) by an as yet unknown mechanism. The high levels of Lp(a) in the nephrotic syndrome could cause glomerular injury as well as increase the risk for atherosclerosis and thrombotic events associated with this disorder. C1 NHLBI,BETHESDA,MD 20892. RP WANNER, C (reprint author), UNIV HOSP FREIBURG,DEPT MED,DIV NEPHROL,HUGSTETTERSTR 55,W-7800 FREIBURG,GERMANY. NR 42 TC 143 Z9 144 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 15 PY 1993 VL 119 IS 4 BP 263 EP 269 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LV525 UT WOS:A1993LV52500002 PM 8328733 ER PT J AU JUVONEN, RO IWASAKI, M SUEYOSHI, T NEGISHI, M AF JUVONEN, RO IWASAKI, M SUEYOSHI, T NEGISHI, M TI STRUCTURAL ALTERATION OF MOUSE P450COH BY MUTATION OF GLYCINE-207 TO PROLINE - SPIN EQUILIBRIUM, ENZYME-KINETICS, AND HEAT SENSITIVITY SO BIOCHEMICAL JOURNAL LA English DT Article ID HELIX-FORMING TENDENCIES; AXIAL LIGAND TRANS; C-PEPTIDE HELIX; AMINO-ACID; ALPHA-HELICES; PROTEIN; CYTOCHROMES-P450; CYTOCHROME-P-450; COMPLEXES; RESIDUES AB Mouse cytochrome P450coh is a high-spin haem protein which specifically catalyses coumarin 7-hydroxylase activity. A mutation of Gly-207 to Pro shifts the P450coh completely to the low-spin form, indicating that the sixth axial position of the haem is hexaco-ordinated with a water molecule in the mutant G207P. Moreover, the G207P mutation increases the K(m) value for coumarin 7-hydroxylase activity 100-fold and the K(d) value for coumarin binding 200-fold. Conversely, the mutation decreases the K(i) and K(d) values 10- and 20-fold respectively when testosterone, a larger molecule, is used as a substrate. The results, therefore, are consistent with an idea that the substrate pocket may be larger in the mutant G207P than in the wild-type cytochrome P-450. A Gly-207 to Ala mutation (G207A) of P450coh (G207A), on the other hand, affects neither the spectral nor the enzymic properties of P450coh. Pro-207, through cis/trans isomerization or formation of a kink, may confer on the G207P a structural alteration of its substrate-haem pocket. Our previous studies [Iwasaki, Juvonen, Lindberg and Negishi (1991) J. Biol. Chem. 266, 3380-3382; Juvonen, Iwasaki and Negishi (1991) J. Biol. Chem. 266, 16431-16435] show that the residue at position 209 in P450coh resides close to the sixth axial position of the haem, and the spin equilibrium of the cytochrome P-450 shifts toward the high-spin state as residue 209 becomes more hydrophobic and larger. A Gly-207 to Pro mutation, therefore, results in the creation of a larger substrate pocket in the mutant cytochrome P-450 by altering the protein structure around residue 209 so that a water molecule and testosterone can be accommodated. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NR 26 TC 8 Z9 8 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 AUG 15 PY 1993 VL 294 BP 31 EP 34 PN 1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LU522 UT WOS:A1993LU52200005 PM 8395817 ER PT J AU BELL, DR PLANT, NJ RIDER, CG NA, L BROWN, S ATEITALLA, I ACHARYA, SK DAVIES, MH ELIAS, E JENKINS, NA GILBERT, DJ COPELAND, NG ELCOMBE, CR AF BELL, DR PLANT, NJ RIDER, CG NA, L BROWN, S ATEITALLA, I ACHARYA, SK DAVIES, MH ELIAS, E JENKINS, NA GILBERT, DJ COPELAND, NG ELCOMBE, CR TI SPECIES-SPECIFIC INDUCTION OF CYTOCHROME-P-450 4A-RNAS - PCR CLONING OF PARTIAL GUINEA-PIG, HUMAN AND MOUSE CYP4A-CDNAS SO BIOCHEMICAL JOURNAL LA English DT Article ID HEPATIC PEROXISOME PROLIFERATION; ACYL-COA OXIDASE; TISSUE-SPECIFIC REGULATION; ACID OMEGA-HYDROXYLASE; GENETIC-LINKAGE MAP; LAURIC ACID; RAT-LIVER; DEPENDENT EXPRESSION; MESSENGER-RNA; CDNA SEQUENCE AB PCR was used to demonstrate the presence of a conserved region and to clone novel members of the cytochrome P-450 4A gene family from guinea pig, human and mouse cDNAs. This strategy is based on the sequences at nucleotides 925-959 and at the haem binding domain (nucleotides 1381-1410) of the rat CYP4A1 gene. Murine Cyp4a clones showed high sequence identity with members of the rat gene family, but CYP4A clones from human and guinea pig were equally similar to the rat/mouse genes, suggesting that the rat/mouse line had undergone gene duplication events after divergence from human and guinea-pig lines. The mouse Cyp4a-12 clone was localized to chromosome 4 using interspecific backcross mapping, in a region of synteny with human chromosome 1. The assignment of the human CYP4A11 gene to chromosome 1 was confirmed by somatic cell hybridization. An RNAase protection assay was shown to discriminate between the murine Cyp4a-10 and Cyp4a-12 cDNAs. Treatment of mice with the potent peroxisome proliferator methylclofenapate (25 mg/kg) induced Cyp4a-10 RNA in liver, and to a lesser extent in kidney; there was no sex difference in this response. Cyp4a-12 RNA was present at high levels in male control liver and kidney samples, and was not induced by treatment with methylclofenapate. However, Cyp4a-12 RNA was present at low levels in control female liver and kidney RNA, and was greatly induced in both organs by methylclofenapate. Guinea pigs were exposed to methylclofenapate (50 mg/kg), but there was no significant induction of the guinea-pig CYP4A13 RNA. These findings are consistent with a species difference in response to peroxisome proliferators between the rat/mouse and the guinea pig. C1 UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DEPT BIOCHEM,NOTTINGHAM NG7 2UH,ENGLAND. QUEEN ELIZABETH HOSP,QUEEN ELIZABETH MED CTR,LIVER UNIT,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. ICI PLC,CENT TOXICOL LAB,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. RP BELL, DR (reprint author), UNIV NOTTINGHAM,DEPT LIFE SCI,NOTTINGHAM NG7 2RD,ENGLAND. RI Plant, Nick/E-4510-2011 OI Plant, Nick/0000-0003-4332-8308 FU NCI NIH HHS [N01-CO-74101]; Wellcome Trust NR 43 TC 74 Z9 78 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 AUG 15 PY 1993 VL 294 BP 173 EP 180 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LU522 UT WOS:A1993LU52200025 PM 8363569 ER PT J AU DORN, LD SUSMAN, EJ AF DORN, LD SUSMAN, EJ TI SERUM AND SALIVA CORTISOL RELATIONS IN ADOLESCENTS DURING PREGNANCY AND THE EARLY POSTPARTUM PERIOD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SALIVA CORTISOL; SERUM CORTISOL; PREGNANCY; ADOLESCENT PREGNANCY ID DEXAMETHASONE SUPPRESSION TEST; BIOCHEMICAL MANIFESTATIONS; ADRENAL-FUNCTION; DEPRESSION; PLASMA; CHILDREN; STRESS; NEUROBIOLOGY; HORMONE; LABOR AB The purpose of this investigation was to examine: (1) relations between serum and saliva cortisol in adolescents in pregnancy and early postpartum and (2) short-term consistency of serum and saliva cortisol across three samples, 20 minutes apart, as well as the long-term consistency from pregnancy to early postpartum. Pregnant adolescents (n = 40), ages 14 to 19 years, were enrolled in this study. Subjects were seen at 20 weeks gestation or earlier (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood samples were drawn at T1 and T3, at 0, 20, and 40 minutes. Saliva samples were collected across the same 40-minute period at T1, T2, and T3. Spearman rho (r(s)) correlation coefficients between serum and saliva ranged from 0.72 to 0.77 (T1), and 0.42 to 0.60 (T3) (p less-than-or-equal-to 0.05). Short-term consistency between serum cortisol samples was 0.86-0.97 at T1 and 0.60-0.82 at T3. Short-term consistency for saliva cortisol samples was 0.70-0.96 at T1, 0.91-0.95 at T2, and 0.64-0.89 at T3. Long-term consistency (T1 to T3) for serum and saliva cortisol was low. Individual differences as well as dramatic changes in the endocrine environment in pregnancy and the early postpartum period may explain the more moderate serum-saliva correlations in the postpartum period. C1 PENN STATE UNIV,BIOBEHAV HLTH PROGRAM,UNIV PK,PA 16802. RP DORN, LD (reprint author), NIH,BLDG 103 S 231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NINR NIH HHS [F31 NRO5965] NR 42 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1993 VL 34 IS 4 BP 226 EP 233 DI 10.1016/0006-3223(93)90076-P PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LV321 UT WOS:A1993LV32100005 PM 8399819 ER PT J AU PERSICO, AM VANDENBERGH, DJ SMITH, SS UHL, GR AF PERSICO, AM VANDENBERGH, DJ SMITH, SS UHL, GR TI DOPAMINE TRANSPORTER GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH POLYSUBSTANCE ABUSE SO BIOLOGICAL PSYCHIATRY LA English DT Note ID SUBSTANCE-ABUSE; RECEPTOR GENE; VULNERABILITY C1 NATL INST DRUG ABUSE, ADDICT RES CTR, MOLEC NEUROBIOL BRANCH, BOX 5180, BALTIMORE, MD 21224 USA. NATL INST DRUG ABUSE, ADDICT RES CTR, ETIOL BRANCH, BALTIMORE, MD USA. JOHNS HOPKINS SCH MED, DEPT NEUROL, BALTIMORE, MD USA. JOHNS HOPKINS SCH MED, DEPT NEUROSCI, BALTIMORE, MD USA. NR 13 TC 54 Z9 54 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1993 VL 34 IS 4 BP 265 EP 267 DI 10.1016/0006-3223(93)90081-N PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LV321 UT WOS:A1993LV32100010 PM 8399824 ER EF