FN Thomson Reuters Web of Science™ VR 1.0 PT J AU ZIEGLER, RG HOOVER, RN PIKE, MC HILDESHEIM, A NOMURA, AMY WEST, DW WUWILLIAMS, AH KOLONEL, LN HORNROSS, PL ROSENTHAL, JF HYER, MB AF ZIEGLER, RG HOOVER, RN PIKE, MC HILDESHEIM, A NOMURA, AMY WEST, DW WUWILLIAMS, AH KOLONEL, LN HORNROSS, PL ROSENTHAL, JF HYER, MB TI MIGRATION PATTERNS AND BREAST-CANCER RISK IN ASIAN-AMERICAN WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; FAT CONSUMPTION; DIETARY-FAT; MORTALITY; JAPANESE; CHINESE; EPIDEMIOLOGY; PREVENTION; ETIOLOGY AB Background: Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites. Purpose: Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women. Methods: A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%). Results: A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate. Conclusions: Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life. Implications: Because heterogeneity in breast cancer in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. NO CALIF CANC CTR,UNION CITY,CA. UNIV HAWAII,CANC RES CTR,EPIDEMIOL PROGRAM,HONOLULU,HI 96822. RP ZIEGLER, RG (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N 443,BETHESDA,MD 20892, USA. NR 36 TC 667 Z9 685 U1 9 U2 31 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 1993 VL 85 IS 22 BP 1819 EP 1827 DI 10.1093/jnci/85.22.1819 PG 9 WC Oncology SC Oncology GA MG530 UT WOS:A1993MG53000011 PM 8230262 ER PT J AU KURATSU, J YOSHIZATO, K YOSHIMURA, T LEONARD, EJ TAKESHIMA, H USHIO, Y AF KURATSU, J YOSHIZATO, K YOSHIMURA, T LEONARD, EJ TAKESHIMA, H USHIO, Y TI QUANTITATIVE STUDY OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN CEREBROSPINAL-FLUID AND CYST FLUID FROM PATIENTS WITH MALIGNANT GLIOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MONOCLONAL-ANTIBODIES; TUMORS; CELLS; SEQUENCE AB Background: Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino acid protein that attracts monocytes. In vitro studies have reported high levels of MCP-1 messenger RNA expression, as well as the presence of MCP-1, in malignant glioma cells. Purpose: Our purpose was to determine whether an MCP-1 assay could be used in a clinical setting 1) to differentiate malignant from benign gliomas and from nontumor disorders of the central nervous system and 2) to detect subarachnoid dissemination of glioma cells. Methods: MCP-1 levels in cerebrospinal fluid (CSF) and cyst fluid were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) that we had previously developed. We measured MCP-1 levels in CSF samples from 19 patients with malignant glioma (glioblastoma, 10; anaplastic astrocytoma, six; anaplastic oligodendroglioma, two; and ependymoblastoma, one), nine patients with benign glioma, and seven patients with nontumor disorders of the central nervous system. Cyst fluids from four patients with malignant glioma (anaplastic astrocytoma) were also tested. The correlation between MCP-1 concentration in the CSF and subarachnoid dissemination of malignant glioma cells was also studied. Results: The MCP-1 concentration (mean +/- SE) in CSF samples from patients with malignant glioma (2.3 +/- 0.4 ng/mL) was significantly higher than that from patients with benign glioma (0.6 +/- 0.1 ng/mL) (P<.01) or from patients with no tumor (0.5 +/- 0.1 ng/mL) (P<.01). Furthermore, CSF samples from patients with subarachnoid dissemination of malignant glioma contained significantly higher amounts of MCP-1 than those from patients without dissemination (P<.05). Cyst fluids from four of the patients with malignant glioma contained high concentrations of MCP-1. Conclusions: These results indicate that MCP-1 is produced by malignant glioma in vivo as well as in vitro and suggest that testing for MCP-1 in CSF may be useful in the clinic to differentiate malignant glioma from benign glioma and to detect subarachnoid dissemination of the tumor cells. Implications: The MCP-1 ELISA in CSF may lead to more accurate diagnosis of malignant glioma and detection of subarachnoid dissemination of tumor cells, facilitating selection of patients with these conditions for appropriate therapy. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC BIOL,IMMUNOBIOL LAB,FREDERICK,MD 21701. RP KURATSU, J (reprint author), KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,1-1-1 HONJYO,KUMAMOTO 860,JAPAN. NR 15 TC 48 Z9 49 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 NOV 17 PY 1993 VL 85 IS 22 BP 1836 EP 1839 DI 10.1093/jnci/85.22.1836 PG 4 WC Oncology SC Oncology GA MG530 UT WOS:A1993MG53000013 PM 8230263 ER PT J AU BUCHER, JR MELNICK, RL HILDEBRANDT, PK AF BUCHER, JR MELNICK, RL HILDEBRANDT, PK TI LACK OF CARCINOGENICITY IN MICE EXPOSED ONCE TO HIGH-CONCENTRATIONS OF 1,3-BUTADIENE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID WORKERS C1 PATHCO INC,GAITHERSBURG,MD. RP BUCHER, JR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 8 TC 2 Z9 3 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 1993 VL 85 IS 22 BP 1866 EP 1867 DI 10.1093/jnci/85.22.1866 PG 2 WC Oncology SC Oncology GA MG530 UT WOS:A1993MG53000020 PM 8230269 ER PT J AU SCHIFFMAN, MH MANOS, MM SHERMAN, ME SCOTT, DR GLASS, AG AF SCHIFFMAN, MH MANOS, MM SHERMAN, ME SCOTT, DR GLASS, AG TI HUMAN PAPILLOMAVIRUS AND CERVICAL INTRAEPITHELIAL NEOPLASIA - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID INFECTION C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21218. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. KAISER PERMANENTE,CTR HLTH RES,PORTLAND,OR. RP SCHIFFMAN, MH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 443,BETHESDA,MD 20892, USA. NR 5 TC 12 Z9 12 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 1993 VL 85 IS 22 BP 1868 EP 1870 DI 10.1093/jnci/85.22.1868-a PG 3 WC Oncology SC Oncology GA MG530 UT WOS:A1993MG53000023 ER PT J AU PEGG, AE BOOSALIS, M SAMSON, L MOSCHEL, RC BYERS, TL SWENN, K DOLAN, ME AF PEGG, AE BOOSALIS, M SAMSON, L MOSCHEL, RC BYERS, TL SWENN, K DOLAN, ME TI MECHANISM OF INACTIVATION OF HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE BY O6-BENZYLGUANINE SO BIOCHEMISTRY LA English DT Article ID DNA-REPAIR METHYLTRANSFERASE; MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; HUMAN O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; HUMAN-TUMOR-CELLS; ESCHERICHIA-COLI; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; ADAPTIVE RESPONSE; CROSS-LINK; ADA GENE AB Human O6-alkylguanine-DNA alkyltransferase was rapidly inactivated by low concentrations of O6-benzylguanine, but the alkyltransferase from the Escherichia coli ogt gene was much less sensitive and alkyltransferases from the E. coli ada gene or from yeast were not affected. O6-Benzyl-2'-deoxyguanosine was less potent than the base, but was still an effective inactivator of the human alkyltransferase and had no effect on the microbial proteins. O6-Allylguanine was somewhat less active, but still gave complete inactivation of both the human and Ogt alkyltransferases at 200 muM in 30 min, slightly affected the Ada protein, and had no effect on the yeast alkyltransferase. O4-Benzylthymidine did not inactivate any of the alkyltransferase proteins tested. Inactivation of the human alkyltransferase by O6-benzylguanine led to the formation of S-benzylcysteine in the protein and to the stoichiometric production of guanine. The rate of guanine formation followed second-order kinetics (k = 600 M-1 s-1). Prior inactivation of the alkyltransferase by reaction with a methylated DNA substrate abolished its ability to convert O6-benzylguanine into guanine. These results indicate that O6-benzylguanine inactivates the protein by acting as a substrate for alkyl transfer and by forming S-benzylcysteine at the acceptor site of the protein. The inability of O6-benzylguanine to inactivate the microbial alkyltransferases may be explained by steric constraints at this site. The reduced effectiveness of the allyl compared to the benzyl derivative is in accord with its expected, lower rate of participation in bimolecular displacement reactions, and its ability to inactivate the Ogt alkyltransferase may be explained by its smaller size permitting access to this active site. These studies unequivocally show that the human alkyltransferase protein can act on low molecular weight substrates lacking the polynucleotide structure. In addition to their use to inactivate the protein, such substrates may also prove useful for the assay of mammalian alkyltransferase. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CARCINOGEN MODIFIED NUCL ACID CHEM SECT,FREDERICK,MD 21702. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. HARVARD UNIV,SCH PUBL HLTH,DEPT MOLEC & CELLULAR TOXICOL,BOSTON,MA 02115. RP PEGG, AE (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,POB 850,HERSHEY,PA 17033, USA. FU NCI NIH HHS [CA-18137, CA-55042]; NIEHS NIH HHS [ES-03926] NR 50 TC 163 Z9 166 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 16 PY 1993 VL 32 IS 45 BP 11998 EP 12006 DI 10.1021/bi00096a009 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG893 UT WOS:A1993MG89300009 PM 8218276 ER PT J AU GROGAN, J SHOU, M ZHOU, D CHEN, S KORZEKWA, KR AF GROGAN, J SHOU, M ZHOU, D CHEN, S KORZEKWA, KR TI USE OF AROMATASE (CYP19) METABOLITE RATIOS TO CHARACTERIZE ELECTRON-TRANSFER FROM NADPH-CYTOCHROME-P450 REDUCTASE SO BIOCHEMISTRY LA English DT Article ID CYTOCHROME P-450 REDUCTASE; HUMAN PLACENTAL AROMATASE; CATALYTIC ACTIVITY; ENZYME-SYSTEM; AROMATIZATION; MICROSOMES; ORGANIZATION; AGGREGATION; OXIDATION; SUBSTRATE AB Aromatase catalyzes the conversion of 4-androstene-3,17-dione to estrogen with the concomitant formation of the minor metabolites 4-androstene-19-hydroxy-3,17-dione (19-hydroxyandrostenedione) and 4-androstene-3,17,19-trione(19-oxoandrostenedione). Microsomes of chinese hamster ovary (CHO) cells expressing human aromatase were isolated to investigate androstenedione metabolism. Relatively greater amounts of the minor metabolites result after limitation of electron flux from NADPH-cytochrome P450 reductase to aromatase. Substitution of NADH for NADPH or limitation of NADPH availability increased minor metabolite formation relative to estrogen formation. Similar changes in metabolite ratios were observed when metabolism was conducted either at high pH (8.3) or in the presence of n-alcohols in the range of 5-200 mM alcohol concentrations. However, conditions of low pH (5.5) or high ionic strength (1 M KCl) resulted in minor changes in metabolite ratios, suggesting little or no effect on electron flux between NADPH-cytochrome P450 reductase and aromatase. Theoretical molar ratios of the resulting metabolites were predicted using a reaction scheme assuming sequential substrate oxidations without reversible intermediate release from the aromatase active site. This model was supported by a close agreement between theoretical and experimental metabolite ratios for a broad range of NADPH concentrations. The results indicate that metabolite ratios provide a sensitive indicator of aromatase-oxidoreductase interactions in the microsomal environment. C1 NIH,BLDG 37,RM 3E24,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,BECKMAN RES INT,DUARTE,CA 91010. FU NCI NIH HHS [CA44735] NR 29 TC 17 Z9 17 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 NOV 16 PY 1993 VL 32 IS 45 BP 12007 EP 12012 DI 10.1021/bi00096a010 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG893 UT WOS:A1993MG89300010 PM 8218277 ER PT J AU ZIMMERMAN, SB AF ZIMMERMAN, SB TI MACROMOLECULAR CROWDING EFFECTS ON MACROMOLECULAR INTERACTIONS - SOME IMPLICATIONS FOR GENOME STRUCTURE AND FUNCTION SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review DE DNA; DNA-BINDING PROTEIN; DNA-PROTEIN INTERACTION; EXCLUDED VOLUME; MACROMOLECULAR CROWDING; NUCLEOID ID REPRESSOR-OPERATOR INTERACTION; HISTONE-LIKE PROTEINS; POLYMER-STIMULATED LIGATION; ESCHERICHIA-COLI CHROMOSOME; MONO-VALENT CATIONS; SINGLE-STRANDED-DNA; BLUNT-END LIGATION; LAMBDA-PR PROMOTER; T4 RNA LIGASE; POLYETHYLENE-GLYCOL RP ZIMMERMAN, SB (reprint author), NIDDKD,MOLEC BIOL LAB,BLDG 5,ROOM 328W,BETHESDA,MD 20892, USA. NR 89 TC 81 Z9 81 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD NOV 16 PY 1993 VL 1216 IS 2 BP 175 EP 185 DI 10.1016/0167-4781(93)90142-Z PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ592 UT WOS:A1993MJ59200001 PM 8241257 ER PT J AU TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J AF TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J TI PRIMARY STRUCTURE AND LENS-SPECIFIC EXPRESSION OF GENES FOR AN INTERMEDIATE FILAMENT PROTEIN AND A BETA-TUBULIN IN CEPHALOPODS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CYTOSKELETON; LENS; INTERMEDIATE FILAMENT; ALPHA-TUBULIN; BETA-TUBULIN; CEPHALOPOD ID CELL BEADED-FILAMENT; FIBER CELL; TRANSGENIC MICE; XENOPUS-LAEVIS; ROD DOMAIN; NEUROFILAMENT PROTEIN; CONSENSUS SEQUENCE; VIMENTIN GENE; TERMINAL END; IF PROTEINS AB Intermediate filament (IF) protein and tubulin cDNAs of cephalopod eye lenses were cloned and sequenced. The rod regions of the deduced IF proteins of the squid and octopus were more similar (68% identical) than were head (33% identical) and tail (40% identical) regions. The rod sequences were closer to squid neuronal IF protein (39% identical) than to any other known IF protein. There was only 31% identity between the rod regions, 21-30% identity between the head regions and 23-32% identity between the tail regions of the present IF proteins of cephalopods and other invertebrates. The rod regions of the cephalopod IF proteins contained the 6 heptads characteristic of nuclear lamins, consistent with an evolutionary relationship between IF proteins and lamins. The present octopus alpha-tubulin was 93% and beta-tubulin was 87% identical to the corresponding tubulins of insects and vertebrates. SDS-PAGE and peptide sequencing indicated that the order of abundance of the cephalopod lens cytoskeletal proteins was IF proteins, actin and tubulins. Northern blot hybridization revealed a 4 kb mRNA for the octopus IF protein and 2.9 and 7.3 kb mRNAs for the squid IF protein; the alpha-tubulin mRNA was about 1.8 kb in the octopus and squid, and the beta-tubulin mRNA was about 2.8 kb in the octopus. The alpha-tubulin mRNA was present in all tissues examined; by contrast, the present beta-tubulin and IF protein mRNAs appeared specialized for lens expression. C1 AN KOLTSOV INST DEV BIOL,MOSCOW,RUSSIA. RP TOMAREV, SI (reprint author), NEI,LMDB,BLDG 6,ROOM 203,BETHESDA,MD 20892, USA. NR 64 TC 36 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD NOV 16 PY 1993 VL 1216 IS 2 BP 245 EP 254 DI 10.1016/0167-4781(93)90151-3 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ592 UT WOS:A1993MJ59200010 PM 8241265 ER PT J AU VONLUBITZ, DKJE PAUL, IA CARTER, M JACOBSON, KA AF VONLUBITZ, DKJE PAUL, IA CARTER, M JACOBSON, KA TI EFFECTS OF N-6-CYCLOPENTYL ADENOSINE AND 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE ON N-METHYL-D-ASPARTATE INDUCED SEIZURES IN MICE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ADENOSINE RECEPTOR AGONIST; ADENOSINE RECEPTOR ANTAGONIST; SEIZURE; NMDA (N-METHYL-D-ASPARTATE); PROTECTION; (MOUSE) ID INDUCED CONVULSIONS; RAT; RELEASE; SLICES; MODULATION; GLUTAMATE AB The effect of the adenosine A(1) receptor agonist N-6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures and progressively increasing mortality were seen at higher doses. Prior administration of CPA resulted either in a delay of seizure onset and unchanged mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the effect of CPX administration resulted in mortality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A(1) receptor agonists may protect against NMDA-evoked seizures and that the adenosine A(1) receptor may be directly involved in these actions. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP VONLUBITZ, DKJE (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 26 TC 59 Z9 59 U1 0 U2 0 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 NOV 16 PY 1993 VL 249 IS 3 BP 265 EP 270 DI 10.1016/0014-2999(93)90521-I PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH525 UT WOS:A1993MH52500003 PM 8287913 ER PT J AU VONLUBITZ, DKJE PAUL, IA BARTUS, RT JACOBSON, KA AF VONLUBITZ, DKJE PAUL, IA BARTUS, RT JACOBSON, KA TI EFFECTS OF CHRONIC ADMINISTRATION OF ADENOSINE A(1) RECEPTOR AGONIST AND ANTAGONIST ON SPATIAL-LEARNING AND MEMORY SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ADENOSINE; XANTHINE; MEMORY; LEARNING; WATER MAZE; (MOUSE) ID ADENYLATE CYCLASE SYSTEM; SYNAPTIC TRANSMISSION; HIPPOCAMPAL SLICES; INHIBITORY-ACTION; L-PIA; CAFFEINE; RAT; A1-RECEPTORS; TRANSIENT; LOCOMOTOR AB Spatial memory acquisition in Morris water maze was tested in C57BL/6 mice. Animals were injected once daily with different doses of either N-6-cyclopentyladenosine (CPA) or 8-cyclopentyl-1,3-dipropylxanthine (CPX). Drugs were administered for 9 days either concurrently with water maze testing (drugs injected 1 h after each trial), or prior to the entire block of trials. In the latter case, 1 day without injections preceded water maze experiments. Chronic administration of CPA resulted in a significant, dose-dependent reduction of target latencies, rapid development of spatial preference, and the absence of animals unable to perform the task. CPX treated animals did not show significant performance changes, and failed to develop spatial preference. Locomotor disturbances were not the cause of the observed effects. Our results indicate that chronic treatment with agents acting at adenosine A(1) receptors results in behavioral effects that are significantly different from those observed following their acute administration. Therefore, particular caution is required in development of adenosine-based strategies targeted at neurodegenerative or cognitive disorders in which chronic treatment is advocated. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. CORTEX PHARMACEUT INC,IRVINE,CA 92718. RP VONLUBITZ, DKJE (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20] NR 46 TC 49 Z9 50 U1 1 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 NOV 16 PY 1993 VL 249 IS 3 BP 271 EP 280 DI 10.1016/0014-2999(93)90522-J PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH525 UT WOS:A1993MH52500004 PM 8287914 ER PT J AU GALDERISI, M BENJAMIN, EJ EVANS, JC DAGOSTINO, RB FULLER, DL LEHMAN, B LEVY, D AF GALDERISI, M BENJAMIN, EJ EVANS, JC DAGOSTINO, RB FULLER, DL LEHMAN, B LEVY, D TI IMPACT OF HEART-RATE AND PR INTERVAL ON DOPPLER INDEXES OF LEFT-VENTRICULAR DIASTOLIC FILLING IN AN ELDERLY COHORT (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ATRIAL CONTRIBUTION; PULSED DOPPLER; ECHOCARDIOGRAPHY; FLOW; PATTERNS; PRELOAD; AGE; PARAMETERS; POPULATION; HUMANS AB The relations of heart rate and PR interval to n Doppler-derived diastolic indexes were examined in 260 men (mean age 75 years) and 462 women (mean age 76 years) from the Framingham Heart Study. Subjects receiving any antihypertensive or cardiac medications were excluded from eligibility; those with mitral stenosis or prosthesis, pace-maker, atrial fibrillation, arrhythmia, left bundle branch block, congestive heart failure, previous myocardial infarction, and technically inadequate Doppler study were also excluded. Peak velocity of early (E) and late (A) diastolic left ventricular (LV) filling, ratio of peak velocities E/A, ratio of time velocity integrals E/A, and atrial filling fraction were studied by multivariable analyses adjusting for age, sex, blood pressure, heart rate and PR interval. Heart rate was a major determinant of all 5 Doppler indexes of diastolic filling; heart rate was inversely associated with peak velocity E, E/A, and time velocity integral E/A, and was directly associated with peak velocity a and atrial filling fraction. PR interval was inversely associated with time velocity integral E/A (p < 0.01) and directly associated with atrial filling fraction. The results were largely unaltered after further adjustment for LV wall thickness, LV end-diastolic diameter and left atrial diameter (in addition to age, sex and blood pressure). Heart rate and PR interval are independent contributors to Doppler-assessed LV diastolic filling in the elderly. The atrial contribution to LV filling depends on its timing in the cardiac cycle and on heart rate. Failure to account for heart rate and PR interval may lead to inappropriate assessment of Doppler diastolic filling. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,S THURBER ST,FRAMINGHAM,MA 01701. BOSTON CITY HOSP,DIV CARDIOL,BOSTON,MA 02118. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02118. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. OI Galderisi, Maurizio/0000-0003-0311-9069; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038] NR 33 TC 54 Z9 56 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1993 VL 72 IS 15 BP 1183 EP 1187 DI 10.1016/0002-9149(93)90991-K PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MF807 UT WOS:A1993MF80700016 PM 8237811 ER PT J AU STAYNER, L STEENLAND, K GREIFE, A HORNUNG, R HAYES, RB NOWLIN, S MORAWETZ, J RINGENBURG, V ELLIOT, L HALPERIN, W AF STAYNER, L STEENLAND, K GREIFE, A HORNUNG, R HAYES, RB NOWLIN, S MORAWETZ, J RINGENBURG, V ELLIOT, L HALPERIN, W TI EXPOSURE-RESPONSE ANALYSIS OF CANCER MORTALITY IN A COHORT OF WORKERS EXPOSED TO ETHYLENE-OXIDE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ETHYLENE OXIDE; LEUKEMIA; MORTALITY; NEOPLASMS; OCCUPATIONAL EXPOSURE ID SISTER-CHROMATID EXCHANGES; CHROMOSOME-ABERRATIONS; RABBIT LYMPHOCYTES; INHALATION; HEMOGLOBIN; LEUKEMIA; HEALTH; MODEL; RISK; RATS AB The authors previously reported results from the largest cohort mortality study of ethylene oxide-exposed workers that has been conducted to date. Here they extend their previous work by quantitatively examining the relation between cancer mortality and ethylene oxide exposure. This study included workers from 13 of the 14 geographically distinct facilities that were included in the previous investigation. These facilities began regularly using ethylene oxide to sterilize medical supplies or spices sometime between 1938 and 1969. Workers were followed from first exposure through December 31, 1987. Historical exposures to ethylene oxide were estimated using a regression model. Standard life-table analysis was used to examine cancer mortality in three categories of cumulative exposure to ethylene oxide. The Cox proportional hazards model was also used to examine cumulative and other measures of ethylene oxide exposure as predictors of cancer mortality. In both the life-table analysis and the Cox model, a positive trend was observed in all lymphatic and hematopoietic cancer mortality for cumulative ethylene oxide exposure. This trend was strengthened when ethylene oxide exposures 10 years prior to death were discounted (lagged) and when the analysis was restricted to neoplasms of lymphoid cell origin. Despite limitations discussed in this paper, the authors believe that these findings provide some support for the hypothesis that exposure to ethylene oxide increases the risk of mortality from lymphatic and hematopoietic neoplasms. The authors intend to continue follow-up of this relatively young cohort, which may allow more definitive conclusions to be drawn in the future. C1 NCI,ATLANTA,GA. INT CHEM WORKERS UNION,CTR WORKERS HLTH & SAFETY EDUC,CINCINNATI,OH. RP STAYNER, L (reprint author), NIOSH,ROBERT A TAFT LABS,MS C-15,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 41 TC 33 Z9 35 U1 2 U2 6 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1993 VL 138 IS 10 BP 787 EP 798 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ML239 UT WOS:A1993ML23900002 PM 8237967 ER PT J AU HO, GYF NOMURA, AMY NELSON, K LEE, H BLATTNER, WA AF HO, GYF NOMURA, AMY NELSON, K LEE, H BLATTNER, WA TI DECLINING SEROPREVALENCE AND TRANSMISSION OF HLTV-1 IN JAPANESE FAMILIES WHO EMIGRATED TO HAWAII - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 KUAKINI MED CTR,HONOLULU,HI 96817. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. ABBOTT LABS,DIV DIAGNOST,N CHICAGO,IL 60064. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP HO, GYF (reprint author), ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY 10461, USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1993 VL 138 IS 10 BP 900 EP 901 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ML239 UT WOS:A1993ML23900012 ER PT J AU MCDOWELL, GA COWAN, TM BLITZER, MG GREENE, CL AF MCDOWELL, GA COWAN, TM BLITZER, MG GREENE, CL TI INTRAFAMILIAL VARIABILITY IN HURLER-SYNDROME AND SANFILIPPO SYNDROME TYPE-A - IMPLICATIONS FOR EVALUATION OF NEW THERAPIES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE MUCOPOLYSACCHARIDOSES; HURLER SYNDROME; SANFILIPPO SYNDROME TYPE-A; INTRAFAMILIAL VARIABILITY; LYSOSOMAL STORAGE ID METACHROMATIC LEUKODYSTROPHY; GENETIC-HETEROGENEITY AB Intrafamilial variability has not been reported previously in Hurler syndrome or Sanfilippo syndrome type A. We describe two families in which sibs with comparable deficiencies of alpha-iduronidase (Hurler) or sulfamidase (Sanfilippo type A) activities in vitro nonetheless have divergence in clinical severity and disease progression. These cases underscore the need for caution in counseling as well as the limitations of using sibs as controls in evaluating the outcome of treatment. (C) 1993 Wiley-Liss, Inc. C1 UNIV COLORADO,CHILDRENS HOSP,HLTH SCI CTR,IMD CLIN,1056 E 19TH AVE,BOX B153,DENVER,CO 80218. UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV HUMAN GENET,BALTIMORE,MD 21201. NICHHD,HUMAN GENET BRANCH,ROCKVILLE,MD. NR 11 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 15 PY 1993 VL 47 IS 7 BP 1092 EP 1095 DI 10.1002/ajmg.1320470732 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ME487 UT WOS:A1993ME48700031 PM 7507293 ER PT J AU WADHWANI, KC FUKUYAMA, R GIORDANO, T RAPOPORT, SI CHANDRASEKARAN, K AF WADHWANI, KC FUKUYAMA, R GIORDANO, T RAPOPORT, SI CHANDRASEKARAN, K TI QUANTITATIVE REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION OF GLUCOSE-TRANSPORTER-1 MESSENGER-RNA LEVELS IN RAT-BRAIN MICROVESSELS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MESSENGER-RNA; GENE-EXPRESSION; BARRIER; QUANTIFICATION; PROTEIN; DISEASE; PCR RP WADHWANI, KC (reprint author), NIA,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 29 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 1993 VL 215 IS 1 BP 134 EP 141 DI 10.1006/abio.1993.1565 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MG086 UT WOS:A1993MG08600020 PM 7507649 ER PT J AU EVERHART, JE AF EVERHART, JE TI CONTRIBUTIONS OF OBESITY AND WEIGHT-LOSS TO GALLSTONE DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BILIARY CHOLESTEROL SATURATION; GASTRIC BYPASS-SURGERY; LOW-CALORIE DIET; GALLBLADDER-DISEASE; RISK-FACTORS; PHYSICAL-ACTIVITY; LIPID-COMPOSITION; MORBIDLY OBESE; GALL-STONES; RAPID LOSS AB Objective: To examine the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues. Data Sources and Extraction: Original reports obtained through a MEDLINE search from 1966 to 1992 on gallstones plus obesity or reducing diets, supplemented by a manual search of bibliographies, a Current Contents title search from 1991 to 1992 on gallstones and gallbladder, and expert opinion. Only studies of humans were cited. Data Synthesis: For women, but less so for men, obesity is a strong risk factor for gallstones, and this risk is increased during weight loss. Between 10% and 25% of obese men and women may develop gallstones within a few months of beginning a very low calorie diet, and perhaps one third of these will develop symptoms of gallstones. Persons with the highest body mass index before weight loss and those who lose weight most rapidly appear to be at the greatest risk for gallstones. Treatment with ursodeoxycholic acid (ursodiol) during weight loss dieting is the only proven prevention for the formation of gallstones. Issues to be resolved include how different diets affect the risk for developing gallstones, the identification of other risk factors for gallstone formation during weight loss, the effect of weight loss among people with preexisting gallstones, and the optimum means of preventing gallstones during weight loss. Conclusions: During weight loss, particularly-among the obese, an increased risk exists for symptomatic gallstone formation. This acute risk offers the opportunity to investigate the cause of gallstones and possibly to prevent them. RP EVERHART, JE (reprint author), NIDDKD,5333 WESTBARD AVE,ROOM 3A-10,WESTWOOD BLDG,BETHESDA,MD 20892, USA. RI Biguzzi, Felipe/E-4724-2015 NR 58 TC 126 Z9 129 U1 0 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 15 PY 1993 VL 119 IS 10 BP 1029 EP 1035 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MG672 UT WOS:A1993MG67200010 PM 8214980 ER PT J AU SAITO, K QUEARRY, BJ SAITO, M NOWAK, TS MARKEY, SP HEYES, MP AF SAITO, K QUEARRY, BJ SAITO, M NOWAK, TS MARKEY, SP HEYES, MP TI KYNURENINE 3-HYDROXYLASE IN BRAIN - SPECIES ACTIVITY DIFFERENCES AND EFFECT OF GERBIL CEREBRAL-ISCHEMIA SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID QUINOLINIC ACID; INDOLEAMINE 2,3-DIOXYGENASE; NEUROACTIVE KYNURENINES; CEREBROSPINAL-FLUID; RAT-BRAIN; INDOLEAMINE-2,3-DIOXYGENASE; SERUM C1 UNIV TENNESSEE CTR HLTH SCI,DEPT NEUROL,MEMPHIS,TN 38163. RP SAITO, K (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,BETHESDA,MD 20892, USA. NR 22 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1993 VL 307 IS 1 BP 104 EP 109 DI 10.1006/abbi.1993.1567 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG683 UT WOS:A1993MG68300017 PM 8239646 ER PT J AU KOSA, K MEYERS, K DE LUCA, LM AF KOSA, K MEYERS, K DE LUCA, LM TI TRANSFORMATION OF NIH3T3 CELLS WITH RAS ONCOGENES ABROGATES THE RETINOIC ACID INDUCTION OF TISSUE TRANSGLUTAMINASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INDUCED EXPRESSION; GENE-EXPRESSION; NIH-3T3 CELLS; GROWTH; HEPATOCYTES; MACROPHAGES; FIBROBLASTS; APOPTOSIS; SURFACE; INVIVO C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. OI Kosa, Karolina/0000-0001-7867-2403 NR 31 TC 13 Z9 13 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 15 PY 1993 VL 196 IS 3 BP 1025 EP 1033 DI 10.1006/bbrc.1993.2354 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG310 UT WOS:A1993MG31000002 PM 7504461 ER PT J AU DANILENKO, M WORLAND, P CARLSON, B SAUSVILLE, EA SHARONI, Y AF DANILENKO, M WORLAND, P CARLSON, B SAUSVILLE, EA SHARONI, Y TI SELECTIVE EFFECTS OF MASTOPARAN ANALOGS - SEPARATION OF G-PROTEIN-DIRECTED AND MEMBRANE-PERTURBING ACTIVITIES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ARACHIDONIC-ACID RELEASE; PHOSPHOINOSITIDE HYDROLYSIS; AMPHIPHILIC PEPTIDES; BOUND CONFORMATION; HL-60 CELLS; WASP VENOM; KINASE-C; RECEPTOR; NA,K-ATPASE; ANTAGONISTS C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,CLIN BIOCHEM UNIT,IL-84105 BEER SHEVA,ISRAEL. NCI,BIOL CHEM LAB,BETHESDA,MD 20892. RI DANILENKO, MICHAEL/F-2283-2012; OI Danilenko, Michael/0000-0001-9466-6169 NR 24 TC 35 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 15 PY 1993 VL 196 IS 3 BP 1296 EP 1302 DI 10.1006/bbrc.1993.2393 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG310 UT WOS:A1993MG31000041 PM 8250884 ER PT J AU VU, ND WAGNER, PD AF VU, ND WAGNER, PD TI STIMULATION OF SECRETION IN PERMEABILIZED PC12 CELLS BY ADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE - POSSIBLE INVOLVEMENT OF NUCLEOSIDE DIPHOSPHATE KINASE SO BIOCHEMICAL JOURNAL LA English DT Article ID NUCLEOTIDE-BINDING-PROTEINS; NOREPINEPHRINE SECRETION; ADENYLATE-CYCLASE; PC-12 CELLS; GUANINE; ACTIVATION; RELEASE; GTP; RECEPTOR; ATP AB The addition of Ca2+, adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) to digitonin-permeabilized PCl2 cells stimulates noradrenaline secretion. Both ATP[S] and GTP[S] stimulate release in the absence of Ca2+. Whereas ADP and adenosine 5'-[betagamma-imido]triphosphate inhibited ATP[S]-stimulated release, they did not inhibit Ca2+-stimulated release even in the absence of added ATP. This suggests that the kinase which uses ATP[S] to induce secretion may not play an essential role in Ca2+-Stimulated release. As GTP[S]-stimulated and ATP[S]-stimulated secretions were not additive, it seemed possible that stimulation by ATP[S] might in part result from the thiophosphorylation of GDP by nucleoside-diphosphate (NDP) kinase to form GTP[S]. The following results are consistent with this possibility. (1) A low concentration of GDP increased ATP[S]-stimulated secretion, but not GTP[S]-stimulated or Ca2+-stimulated secretion. (2) A variety of ribo- and deoxyribo-nucleoside di- and tri-phosphates inhibited ATP[S]-stimulated secretion, but not GTP[S]-stimulated or Ca2+-stimulated secretion. Thus, like NDP kinase, the kinase which uses ATP[S] to cause noradrenaline release appears to have a very low specificity for ATP. (3) Incubation of permeabilized cells in a sucrose-containing buffer resulted in the preferential loss of ATP[S]-stimulated secretion and a decrease in the level of NDP kinase. The addition of rat liver NDP kinase to those depleted cells partially restored ATP[S]-stimulated secretion. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 29 TC 11 Z9 11 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 NOV 15 PY 1993 VL 296 BP 169 EP 174 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ595 UT WOS:A1993MJ59500024 PM 8250839 ER PT J AU MULLEN, CA ANDERSON, KD BLAESE, RM AF MULLEN, CA ANDERSON, KD BLAESE, RM TI SPLENECTOMY AND OR BONE-MARROW TRANSPLANTATION IN THE MANAGEMENT OF THE WISKOTT-ALDRICH SYNDROME - LONG-TERM FOLLOW-UP OF 62 CASES SO BLOOD LA English DT Article ID STATES C1 CHILDRENS HOSP LOS ANGELES,DEPT SURG,LOS ANGELES,CA. RP MULLEN, CA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 27 TC 110 Z9 110 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 BP 2961 EP 2966 PG 6 WC Hematology SC Hematology GA MH010 UT WOS:A1993MH01000005 PM 8219187 ER PT J AU HESTDAL, K WELTE, K LIE, SO KELLER, JR RUSCETTI, FW ABRAHAMSEN, TG AF HESTDAL, K WELTE, K LIE, SO KELLER, JR RUSCETTI, FW ABRAHAMSEN, TG TI SEVERE CONGENITAL NEUTROPENIA - ABNORMAL GROWTH AND DIFFERENTIATION OF MYELOID PROGENITORS TO GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) BUT NORMAL RESPONSE TO G-CSF PLUS STEM-CELL FACTOR SO BLOOD LA English DT Article ID INFANTILE GENETIC AGRANULOCYTOSIS; FACTOR-BETA; GRANULOPOIESIS; MYELOPOIESIS; INVITRO; PROLIFERATION; FACTOR-BETA-1; PATIENT; LIGAND; SERUM C1 NATL HOSP NORWAY,NATL HOSP OSLO,DEPT PEDIAT,OSLO 1,NORWAY. MED SCH HANNOVER,CHILDRENS CLIN,DEPT PEDIAT HEMATOL & ONCOL,HANNOVER,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP INC,FREDERICK,MD 21701. RP HESTDAL, K (reprint author), NATL HOSP NORWAY,NATL HOSP OSLO,DEPT PEDIAT RES,N-0027 OSLO,NORWAY. NR 34 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 BP 2991 EP 2997 PG 7 WC Hematology SC Hematology GA MH010 UT WOS:A1993MH01000009 PM 7693032 ER PT J AU SAELMAN, EUM HORTON, LF BARNES, MJ GRALNICK, HR HESE, KM NIEUWENHUIS, HK DEGROOT, PG SIXMA, JJ AF SAELMAN, EUM HORTON, LF BARNES, MJ GRALNICK, HR HESE, KM NIEUWENHUIS, HK DEGROOT, PG SIXMA, JJ TI PLATELET-ADHESION TO CYANOGEN-BROMIDE FRAGMENTS OF COLLAGEN-ALPHA-1(I) UNDER FLOW CONDITIONS SO BLOOD LA English DT Article ID COLLAGEN TYPE-I; GLYCOPROTEIN-IA; VONWILLEBRAND-FACTOR; REACTIVE SITES; EXTRACELLULAR-MATRIX; DEPENDENT ADHESION; AGGREGATORY SITES; IDENTIFICATION; RECEPTOR; COMPLEX C1 UNIV UTRECHT HOSP,DEPT HAEMATOL,3511 GV UTRECHT,NETHERLANDS. STRANGEWAYS RES LAB,CAMBRIDGE CB1 4RN,ENGLAND. NIH,BETHESDA,MD 20892. NR 29 TC 29 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 BP 3029 EP 3033 PG 5 WC Hematology SC Hematology GA MH010 UT WOS:A1993MH01000014 PM 8219194 ER PT J AU AGARWAL, R DOREN, S HICKS, B DUNBAR, CE AF AGARWAL, R DOREN, S HICKS, B DUNBAR, CE TI LONG-TERM CULTURE OF CML MARROW ON STEM-CELL FACTOR-DEFICIENT STROMA FAVORS BENIGN PROGENITORS SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,MED CTR,CINCINNATI,OH. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A382 EP A382 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201509 ER PT J AU ANAGNOSTOU, A LIU, Z STEINER, M CHIN, K LEE, ES KESSIMIAN, N NOGUCHI, CT AF ANAGNOSTOU, A LIU, Z STEINER, M CHIN, K LEE, ES KESSIMIAN, N NOGUCHI, CT TI ERYTHROPOIETIN RECEPTOR MESSENGER-RNA EXPRESSION IN HUMAN ENDOTHELIAL-CELLS SO BLOOD LA English DT Meeting Abstract C1 MEM HOSP,PAWTUCKET,RI 02860. BROWN UNIV,SCH MED,DIV HEMATOL ONCOL,PROVIDENCE,RI 02912. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A227 EP A227 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200893 ER PT J AU BOCK, TA DUNBAR, CE ORLIC, D BODINE, DM AF BOCK, TA DUNBAR, CE ORLIC, D BODINE, DM TI TRANSGENIC SCID MICE CONTAINING THE HUMAN IL-3, GM-CSF, AND SCF GENES AS A MODEL FOR HUMAN HEMATOPOIESIS SO BLOOD LA English DT Meeting Abstract C1 NIH,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A457 EP A457 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201810 ER PT J AU BODINE, DM SEIDEL, NE ORLIC, D NIENHUIS, AW AF BODINE, DM SEIDEL, NE ORLIC, D NIENHUIS, AW TI ADMINISTRATION OF G-CSF AND SCF TO SPLENECTOMIZED MICE INCREASES THE NUMBER OF PERIPHERAL-BLOOD STEM-CELLS WHICH ARE EFFICIENTLY TRANSDUCED BY RETROVIRUSES SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A314 EP A314 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201239 ER PT J AU BRODSKY, RA JANE, SM VANIN, EF PETERS, TR SHIMADA, T MEDOF, ME NIENHUIS, AW AF BRODSKY, RA JANE, SM VANIN, EF PETERS, TR SHIMADA, T MEDOF, ME NIENHUIS, AW TI PURIFIED GPI-ANCHORED CD4 AS A RECEPTOR FOR HIV-MEDIATED GENE-TRANSFER SO BLOOD LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD USA. NIPPON MED COLL, DEPT BIOCHEM & MOLEC BIOL, TOKYO 113, JAPAN. CASE WESTERN RESERVE UNIV, INST PATHOL, CLEVELAND, OH 44106 USA. RI Jane, Stephen/D-6659-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A453 EP A453 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201794 ER PT J AU BROWN, KE GREEN, SW GALLINELLA, G ANDERSON, S YOUNG, NS ANDERSON, DC FIKES, JD BAIN, FT CARLSON, CS OSULLIVAN, MG AF BROWN, KE GREEN, SW GALLINELLA, G ANDERSON, S YOUNG, NS ANDERSON, DC FIKES, JD BAIN, FT CARLSON, CS OSULLIVAN, MG TI ISOLATION OF A NOVEL SIMIAN PARVOVIRUS (SPV) FROM CYNOMOLOGUS MONKEYS WITH FATAL ANEMIA - AN ANIMAL-MODEL FOR HUMAN B19 PARVOVIRUS INFECTION SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27103. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A311 EP A311 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201228 ER PT J AU BROWN, KE GREEN, SW DEMAYOLO, JA BELLANTI, JA SMITH, SD SMITH, TJ YOUNG, NS AF BROWN, KE GREEN, SW DEMAYOLO, JA BELLANTI, JA SMITH, SD SMITH, TJ YOUNG, NS TI CONGENITAL INFECTION WITH B19 PARVOVIRUS ASSOCIATED WITH CONSTITUTIONAL ANEMIA AND PURE RED-CELL APLASIA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC 20007. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV COLORADO,DENVER,CO 80202. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A311 EP A311 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201227 ER PT J AU BROWN, KE GALLINELLA, G HIBBS, JR ANDERSON, SM LEHMAN, EH MCCARTHY, M YOUNG, NS AF BROWN, KE GALLINELLA, G HIBBS, JR ANDERSON, SM LEHMAN, EH MCCARTHY, M YOUNG, NS TI GENETIC ABSENCE OF THE VIRAL RECEPTOR FOR B19 PARVOVIRUS BLOOD GROUP-P ANTIGEN CONFERS RESISTANCE TO VIRAL-INFECTION SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. AMER RED CROSS,NO OHIO BLOOD CTR,BETHESDA,MD 20814. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A175 EP A175 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200686 ER PT J AU BUSQUE, L MARAGH, M DEHART, D MCGARIGLE, C VOSE, J ARMITAGE, J MEISINGER, D WHEELER, C GAINES, L BELANGER, R HABEL, F DUNBAR, C CHAMPAGNE, M GROSS, W WEINSTEIN, H ANTIN, JH GILLIAND, DG AF BUSQUE, L MARAGH, M DEHART, D MCGARIGLE, C VOSE, J ARMITAGE, J MEISINGER, D WHEELER, C GAINES, L BELANGER, R HABEL, F DUNBAR, C CHAMPAGNE, M GROSS, W WEINSTEIN, H ANTIN, JH GILLIAND, DG TI CLONALITY OF BONE-MARROW REPOPULATION AFTER ALLOGENEIC AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION (ABMT) SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. UNIV NEBRASKA,OMAHA,NE 68182. NHLBI,BETHESDA,MD 20892. HOP MAISON NEUVE ROSEMONT,MONTREAL H1T 2M4,QUEBEC,CANADA. HOP ST JUSTINE,MONTREAL H3T 1C5,QUEBEC,CANADA. NR 0 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A457 EP A457 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201811 ER PT J AU CARTER, CS WALKER, R MAY, FM LARSON, M WANNEBO, CM CHANG, L LEITMAN, SF BLAESE, RM METCALF, J DAVEY, R MULLEN, CA LANE, HC KLEIN, HG AF CARTER, CS WALKER, R MAY, FM LARSON, M WANNEBO, CM CHANG, L LEITMAN, SF BLAESE, RM METCALF, J DAVEY, R MULLEN, CA LANE, HC KLEIN, HG TI EXPANSION OF SYNGENEIC T-LYMPHOCYTES FOR ADOPTIVE IMMUNOTHERAPY IN TWINS DISCORDANT FOR HIV-INFECTION SO BLOOD LA English DT Meeting Abstract C1 NIAID,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A416 EP A416 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201645 ER PT J AU CLARK, HM YANO, T SANDER, CA OTSUKI, T HARRIS, C LONGO, DL JAFFE, ES RAFFELD, M AF CLARK, HM YANO, T SANDER, CA OTSUKI, T HARRIS, C LONGO, DL JAFFE, ES RAFFELD, M TI GENETIC LESIONS INVOLVED IN THE PROGRESSION OF FOLLICULAR LYMPHOMA SO BLOOD LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A46 EP A46 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200172 ER PT J AU COLEMAN, MB ADAMS, JG SMITH, CM STEINBERG, MH AF COLEMAN, MB ADAMS, JG SMITH, CM STEINBERG, MH TI MODULATION OF HB KOLN DISEASE BY AN ADDITIONAL MUTATION - HB MEDICINE LAKE SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR,JACKSON,MS 39216. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV MISSISSIPPI,JACKSON,MS 39216. NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A222 EP A222 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200872 ER PT J AU COTTLERFOX, M SINK, BS YU, M LEITMAN, SF DUNBAR, CE AF COTTLERFOX, M SINK, BS YU, M LEITMAN, SF DUNBAR, CE TI MOBILIZATION AND COLLECTION OF PERIPHERAL-BLOOD STEM-CELLS (PBSC) FOR AUTOLOGOUS TRANSPLANT IN MULTIPLE-MYELOMA (MM) USING INTRAVENOUS G-CSF AND CYCLOPHOSPHAMIDE (CY) SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A265 EP A265 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201043 ER PT J AU DANCIS, A YUAN, DS HAILE, D KLAUSNER, RD AF DANCIS, A YUAN, DS HAILE, D KLAUSNER, RD TI A YEAST MODEL DEMONSTRATES A REQUIREMENT FOR COPPER IN IRON TRANSPORT SO BLOOD LA English DT Meeting Abstract C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A94 EP A94 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200362 ER PT J AU DONAHUE, RE KESSLER, SW KIRBY, MR AGRICOLA, BA DUNBAR, CE SELLERS, SE MACKALL, CL BARE, CV GRESS, RE NIENHUIS, AW LANSDORP, PM AF DONAHUE, RE KESSLER, SW KIRBY, MR AGRICOLA, BA DUNBAR, CE SELLERS, SE MACKALL, CL BARE, CV GRESS, RE NIENHUIS, AW LANSDORP, PM TI AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN NONHUMAN-PRIMATES USING A SUBPOPULATION OF CD34+ CELLS EXPRESSING THY-1 SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. BRITISH COLUMBIA CANC RES CTR,TERRY FOX LAB,VANCOUVER V5Z 1L3,BC,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A297 EP A297 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201174 ER PT J AU DUNBAR, CE OSHAUGHNESSY, JA COTTLERFOX, M CARTER, CS DOREN, S COWAN, KH LEITMAN, SF WILSON, W YOUNG, NS NIENHUIS, AW AF DUNBAR, CE OSHAUGHNESSY, JA COTTLERFOX, M CARTER, CS DOREN, S COWAN, KH LEITMAN, SF WILSON, W YOUNG, NS NIENHUIS, AW TI TRANSPLANTATION OF RETROVIRALLY-MARKED CD34+ BONE-MARROW AND PERIPHERAL-BLOOD CELLS IN PATIENTS WITH MULTIPLE-MYELOMA OR BREAST-CANCER SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A217 EP A217 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200853 ER PT J AU ELBENNA, J CHANOCK, SJ CHRISTENSEN, BL FAUST, LP BABIOR, BM AF ELBENNA, J CHANOCK, SJ CHRISTENSEN, BL FAUST, LP BABIOR, BM TI THE PHOSPHORYLATION OF P47PHOX, A CYTOSOLIC COMPONENT OF THE RESPIRATORY BURST OXIDASE SO BLOOD LA English DT Meeting Abstract C1 SCRIPPS RES INST, LA JOLLA, CA USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A187 EP A187 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200732 ER PT J AU ELWOOD, PC PRICE, K SAIKAWA, Y PACHECO, P CHUNG, K AF ELWOOD, PC PRICE, K SAIKAWA, Y PACHECO, P CHUNG, K TI CHARACTERIZATION OF THE HUMAN KB CELL FOLATE RECEPTOR GENE - DIFFERENTIAL PROMOTER UTILIZATION AND ALTERNATIVE SPLICING SO BLOOD LA English DT Meeting Abstract C1 NCI,DCT,COP,MB,BETHESDA,MD 20892. RI Pacheco, Pablo/I-6762-2016 OI Pacheco, Pablo/0000-0001-5692-2627 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A93 EP A93 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200358 ER PT J AU ENSOLI, B MARKHAM, P RAFFELD, M BARILLARI, G ZON, G GALLO, RC AF ENSOLI, B MARKHAM, P RAFFELD, M BARILLARI, G ZON, G GALLO, RC TI BASIC FIBROBLAST GROWTH-FACTOR (BFGF) MEDIATES THE GROWTH AND ANGIOGENIC ACTIVITY OF AIDS-KAPOSIS SARCOMA (KS)-DERIVED SPINDLE CELLS AND SYNERGIES WITH HIV-1 TAT PROTEIN IN INDUCING KS-LIKE LESIONS IN MICE SO BLOOD LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. ADV BIOSCI INC,KENSINGTON,MD. LYNX THERAPEUT INC,FOSTER CITY,CA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A453 EP A453 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201795 ER PT J AU EYSTER, ME FRIED, MW DIBISCEGLIE, AM GOEDERT, JJ AF EYSTER, ME FRIED, MW DIBISCEGLIE, AM GOEDERT, JJ TI HCV RNA IN HEMOPHILIACS WITH ANTIBODY TO HEPATITIS-C VIRUS (HCV) - RELATIONSHIP TO HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION AND LIVER-FAILURE SO BLOOD LA English DT Meeting Abstract C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A453 EP A453 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201796 ER PT J AU FIBACH, E KOLLIA, P SCHECHTER, AN NOGUCHI, CT RODGERS, GP AF FIBACH, E KOLLIA, P SCHECHTER, AN NOGUCHI, CT RODGERS, GP TI HEMIN ENHANCES FETAL HEMOGLOBIN IN CULTURED ERYTHROID PRECURSORS DERIVED FROM NORMAL INDIVIDUALS AND PATIENTS WITH BETA-GLOBINOPATHIES SO BLOOD LA English DT Meeting Abstract C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A312 EP A312 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201230 ER PT J AU FIBACH, E SCHECHTER, AN NOGUCHI, CT RODGERS, GP AF FIBACH, E SCHECHTER, AN NOGUCHI, CT RODGERS, GP TI EFFECTS OF ERYTHROPOIETIN ON FETAL HEMOGLOBIN PRODUCTION BY CULTURED HUMAN ERYTHROID-CELLS SO BLOOD LA English DT Meeting Abstract C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A222 EP A222 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200871 ER PT J AU FRAME, JN SORENSEN, JM QASHU, N VENA, D CHRISTIAN, M CHUN, HG CHESON, BD AF FRAME, JN SORENSEN, JM QASHU, N VENA, D CHRISTIAN, M CHUN, HG CHESON, BD TI TUMOR LYSIS SYNDROME (TLS) IN PATIENTS RECEIVING FLUDARABINE (F) FOR CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A139 EP A139 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200539 ER PT J AU FREEMAN, G BORRIELLO, F HODES, R GRIBBEN, J GRAY, G NADLER, L SHARPE, A AF FREEMAN, G BORRIELLO, F HODES, R GRIBBEN, J GRAY, G NADLER, L SHARPE, A TI ANTIGEN-PRESENTING CELLS ISOLATED FROM B7-1 DEFICIENT MICE USE AN ALTERNATIVE CTLA4 COUNTER-RECEPTOR, B7-2, TO COSTIMULATE T-CELL ACTIVATION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A323 EP A323 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201277 ER PT J AU FUCHAROEN, S SIRITANARATKUL, N WINICHAGOON, P SIRIBOON, W CHOWTHAWORN, J MUANGSUP, W CHAICHAROEN, S POOLSUP, N CHINDAVIJAK, B POOTRAKUL, P PIANKIJAGUM, A SCHECHTER, AN RODGERS, GP AF FUCHAROEN, S SIRITANARATKUL, N WINICHAGOON, P SIRIBOON, W CHOWTHAWORN, J MUANGSUP, W CHAICHAROEN, S POOLSUP, N CHINDAVIJAK, B POOTRAKUL, P PIANKIJAGUM, A SCHECHTER, AN RODGERS, GP TI HYDROXYUREA INCREASES HBF LEVELS AND IMPROVES THE EFFECTIVENESS OF ERYTHROPOIESIS IN BETA-THALASSEMIA/HBE DISEASE SO BLOOD LA English DT Meeting Abstract C1 SIRIRAJ HOSP,DIV HEMATOL,BANGKOK 7,THAILAND. MAHIDOL UNIV,BANGKOK 10700,THAILAND. NIH,CHEM BIOL LAB,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A357 EP A357 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201410 ER PT J AU GOAD, KE WILSON, O GRALNICK, HR AF GOAD, KE WILSON, O GRALNICK, HR TI COAGULOPATHY ASSOCIATED WITH CRYSTALLINE NIACIN SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,HEMATOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A155 EP A155 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200604 ER PT J AU GRALNICK, HR KRAMER, W MCKEOWN, L GARFINKEL, L PINOT, A WILLIAMS, S AF GRALNICK, HR KRAMER, W MCKEOWN, L GARFINKEL, L PINOT, A WILLIAMS, S TI PLATELET-ADHESION AT HIGH-SHEAR RATES - THE ROLE OF VON-WILLEBRAND FACTOR/GPIB INTERACTION AND A ROLE FOR THE BETA-1 INTEGRIN ALPHA-2-BETA SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A160 EP A160 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200626 ER PT J AU GREVER, M KOPECKY, K HEAD, D FOUCAR, K CASSILETH, P GOLOMB, H HABERMANN, T RAI, K EISENHAUER, E APPELBAUM, F CHESON, B AF GREVER, M KOPECKY, K HEAD, D FOUCAR, K CASSILETH, P GOLOMB, H HABERMANN, T RAI, K EISENHAUER, E APPELBAUM, F CHESON, B TI A RANDOMIZED COMPARISON OF DEOXYCOFORMYCIN (DCF) VERSUS ALPHA-2A INTERFERON (IFN) IN PREVIOUSLY UNTREATED PATIENTS (PTS) WITH HAIRY-CELL LEUKEMIA (HCL) - AN UPDATED REPORT ON THE NCI-SPONSORED INTERGROUP STUDY (SWOG, ECOG, CALGB, NCIC CTG) SO BLOOD LA English DT Meeting Abstract C1 NCI, BETHESDA, MD 20892 USA. SWOG STAT CTR, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. UNIV NEW MEXICO, ALBUQUERQUE, NM 87131 USA. UNIV MIAMI, MIAMI, FL 33152 USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. LONG ISL JEWISH MED CTR, NEW HYDE PK, NY 11042 USA. NCI, CANADA CLIN TRIALS GRP, TORONTO, ON, CANADA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A199 EP A199 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200781 ER PT J AU HANANIA, E FU, S RONINSON, I MECHETNER, E HEGEWISCHBECKER, S ANDREEFF, M BERENSON, R HEIMFELD, S GOTTESMAN, M DEISSEROTH, A AF HANANIA, E FU, S RONINSON, I MECHETNER, E HEGEWISCHBECKER, S ANDREEFF, M BERENSON, R HEIMFELD, S GOTTESMAN, M DEISSEROTH, A TI CDNA FOR THE MULTIDRUG-RESISTANCE (MDR-1) GENE IN A TRANSCRIPTION UNIT OF A SAFETY MODIFIED RETROVIRUS CONFERS IN-VIVO RESISTANCE TO TAXOL ON EARLY PRECURSOR CELLS IN A MOUSE TRANSPLANT MODEL AND ON LONG-TERM CULTURE INITIATING CELLS IN LONG-TERM HUMAN MARROW CULTURE SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. CELL PRO INC,BOTHELL,WA. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A216 EP A216 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200847 ER PT J AU HASEGAWA, S HIRUMA, H UYESAKA, N NOGUCHI, CT SCHECHTER, AN RODGERS, GP AF HASEGAWA, S HIRUMA, H UYESAKA, N NOGUCHI, CT SCHECHTER, AN RODGERS, GP TI FILTERABILITY OF MIXTURES OF SICKLE AND NORMAL ERYTHROCYTES - IMPLICATIONS FOR EXCHANGE-TRANSFUSION THERAPY SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A395 EP A395 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201564 ER PT J AU HASEGAWA, S NOMURA, T IINO, M SHIO, H SCHECHTER, AN UYESAKA, N AF HASEGAWA, S NOMURA, T IINO, M SHIO, H SCHECHTER, AN UYESAKA, N TI DENSE MICROSPHEROCYTES ARISING FROM SPLENIC CONDITIONING MAY PLAY CAUSAL ROLES IN HEMOLYSIS IN HEREDITARY SPHEROCYTOSIS SO BLOOD LA English DT Meeting Abstract C1 NIPPON MED COLL,DEPT INTERNAL MED & PHYSIOL,BUNKYO KU,TOKYO 113,JAPAN. NIDDK,CHEM BIOL LAB,BETHESDA,MD. SHIGA MED CTR ADULT DIS,MORIYAMA,SHIGA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A88 EP A88 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200336 ER PT J AU HUANG, SZ ZENG, YT ZENG, F SHI, O REN, ZR SCHECHTER, AN RODGERS, GP AF HUANG, SZ ZENG, YT ZENG, F SHI, O REN, ZR SCHECHTER, AN RODGERS, GP TI ANALYSIS OF THE EXPRESSION OF DELTA-GLOBIN GENE IN BETA-THALASSEMIA CARRIERS BY DELTA-MESSENGER RNA QUANTITATION SO BLOOD LA English DT Meeting Abstract C1 NIH,CHEM BIOL LAB,BETHESDA,MD 20892. SHANGHAI INST MED GENET,SHANGHAI,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A362 EP A362 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201429 ER PT J AU JAIN, VK SHIMA, T JUDDE, JG MAX, EE MAGRATH, IT AF JAIN, VK SHIMA, T JUDDE, JG MAX, EE MAGRATH, IT TI HIGH-LEVELS OF IMMUNOGLOBULIN ENHANCER ACTIVITY IN EBV TRANSFORMED HUMAN FETAL LIVER PRO-B CELLS MAY BE RELEVANT TO THE GENESIS OF THE TRANSLOCATIONS SEEN IN BURKITTS-LYMPHOMA SO BLOOD LA English DT Meeting Abstract C1 NIH,PEDIAT BRANCH,BETHESDA,MD 20892. US FDA,CBER,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A189 EP A189 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200742 ER PT J AU JAIN, VK WOLFSTENHOLME, J SHIMA, T MAGRATH, IT AF JAIN, VK WOLFSTENHOLME, J SHIMA, T MAGRATH, IT TI TRANS-RETINOIC ACID UP-REGULATES C-MYC IN BURKITT-LYMPHOMA CELL-LINES BY INCREASING ITS TRANSCRIPTIONAL ACTIVITY DIRECTLY AND ALSO VIA THE JUXTAPOSED IMMUNOGLOBULIN ENHANCERS SO BLOOD LA English DT Meeting Abstract C1 NIH,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A47 EP A47 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200176 ER PT J AU KASTENSPORTES, C STEIS, RG WALDMANN, TA AF KASTENSPORTES, C STEIS, RG WALDMANN, TA TI T-CELL RECEPTOR GENE REARRANGEMENT WITH PREFERENTIAL-V-ALPHA BUT DIVERSE-J-ALPHA USAGE IN CLONAL-T-GAMMA LYMPHOPROLIFERATIVE DISEASE SO BLOOD LA English DT Meeting Abstract C1 NCI,METAB BRANCH,BETHESDA,MD 20892. GEORGIA HEMATOL ONCOL CLIN,ATLANTA,GA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A47 EP A47 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200177 ER PT J AU KATEVAS, P MACIEJEWSKI, JP ROSENFELD, S SORRENTINO, BP YOUNG, NS AF KATEVAS, P MACIEJEWSKI, JP ROSENFELD, S SORRENTINO, BP YOUNG, NS TI EXPRESSION OF TUMOR NECROSIS FACTOR-BETA MESSENGER-RNA IN BONE-MARROW OF PATIENTS WITH APLASTIC-ANEMIA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A90 EP A90 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200344 ER PT J AU KIEHNTOPF, M BRACH, MA LICHT, T KIRSCHNING, C WEDEL, E HERRMANN, F AF KIEHNTOPF, M BRACH, MA LICHT, T KIRSCHNING, C WEDEL, E HERRMANN, F TI RIBOZYME MEDIATED CLEAVAGE OF MDR-1 MESSENGER-RNA, A POSSIBLE APPROACH TO REVERSE MULTIPLE-DRUG RESISTANCE IN CANCER-CHEMOTHERAPY SO BLOOD LA English DT Meeting Abstract C1 FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,DEPT MED ONCOL & APPL MOLEC BIOL,D-13122 BERLIN,GERMANY. MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A117 EP A117 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200454 ER PT J AU KIM, IH HAN, JY KIM, JY SCHECHTER, AN RODGERS, GP AF KIM, IH HAN, JY KIM, JY SCHECHTER, AN RODGERS, GP TI IDENTIFICATION OF A NOVEL BETA-CHAIN HEMOGLOBIN-VARIANT [CODON-84(ACC-]AAC), CODON-85(TTT-]AAT)] ASSOCIATED WITH AN UNSTABLE HEMOGLOBINOPATHY IN KOREA SO BLOOD LA English DT Meeting Abstract C1 DONG A UNIV,SCH MED,PUSAN,SOUTH KOREA. NIDDKD,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A471 EP A471 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201866 ER PT J AU KINGMA, DW ANWAR, N BLOCH, AR RAFFELD, M ELBOLKAINY, N JAFFE, ES AF KINGMA, DW ANWAR, N BLOCH, AR RAFFELD, M ELBOLKAINY, N JAFFE, ES TI THE INVESTIGATION OF EPSTEIN-BARR VIRAL SEQUENCES IN 41 CASES OF BURKITTS-LYMPHOMA FROM EGYPT - EPIDEMIOLOGIC CORRELATIONS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NCI,CAIRO,EGYPT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A384 EP A384 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201520 ER PT J AU KOHN, DB WEINBERG, KI PARKMAN, R LENARSKY, C CROOKS, GM SHAW, K HANLEY, ME LAWRENCE, K ANNETT, G BROOKS, JS WARA, D ELDER, M BOWEN, T HERSHFIELD, MS BERENSON, RI MOEN, RC MULLEN, CA BLAESE, RM AF KOHN, DB WEINBERG, KI PARKMAN, R LENARSKY, C CROOKS, GM SHAW, K HANLEY, ME LAWRENCE, K ANNETT, G BROOKS, JS WARA, D ELDER, M BOWEN, T HERSHFIELD, MS BERENSON, RI MOEN, RC MULLEN, CA BLAESE, RM TI GENE-THERAPY FOR NEONATES WITH ADA-DEFICIENT SCID BY RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN ADA CDNA INTO UMBILICAL-CORD CD34+ CELLS SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. ALBERTA CHILDRENS PROV GEN HOSP,CALGARY T2T 5C7,ALBERTA,CANADA. DUKE UNIV,DURHAM,NC 27706. NCI,BETHESDA,MD 20892. NR 0 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A315 EP A315 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201244 ER PT J AU KOLLIA, P FIBACH, E NOGUCHI, CT SCHECHTER, AN AF KOLLIA, P FIBACH, E NOGUCHI, CT SCHECHTER, AN TI HYDROXYUREA AND HEMIN INCREASE BOTH THE TRANSCRIPTION AND THE EFFICIENCY OF RNA PROCESSING OF SOME GLOBIN GENES IN HUMAN ADULT ERYTHROID-CELLS SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A313 EP A313 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201236 ER PT J AU KWAK, LW TAUB, DD DUFFEY, PL BENSINGER, WI LONGO, DL AF KWAK, LW TAUB, DD DUFFEY, PL BENSINGER, WI LONGO, DL TI TRANSFER OF MYELOMA IDIOTYPE-SPECIFIC IMMUNITY FROM AN ACTIVELY IMMUNIZED ALLOGENEIC BONE-MARROW DONOR SO BLOOD LA English DT Meeting Abstract C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A200 EP A200 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200786 ER PT J AU LI, F SEKHSARIA, S LINTON, GF SHALIT, M GALLIN, JI MALECH, HL AF LI, F SEKHSARIA, S LINTON, GF SHALIT, M GALLIN, JI MALECH, HL TI RETROVIRUS TRANSDUCTION CORRECTS SUPEROXIDE GENERATION BY EBV-TRANSFORMED B-CELLS AND MYELOID PROGENITOR CELLS FROM PATIENTS WITH X-LINKED (GP91PHOX) OR P22PHOX FORMS OF CHRONIC GRANULOMATOUS-DISEASE SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A320 EP A320 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201264 ER PT J AU LIU, ZY NOGUCHI, CT AF LIU, ZY NOGUCHI, CT TI TISSUE-SPECIFIC EXPRESSION OF HUMAN ERYTHROPOIETIN RECEPTOR IN TRANSGENIC MICE SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A317 EP A317 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201250 ER PT J AU MACIEJEWSKI, J YOUNG, NS AF MACIEJEWSKI, J YOUNG, NS TI EFFECTS OF HUMAN-IMMUNODEFICIENCY-VIRUS AND ITS ENVELOPE PROTEINS ON HEMATOPOIESIS IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A453 EP A453 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201793 ER PT J AU MACIEJEWSKI, JP KATEVAS, P ANDERSON, S YOUNG, NS AF MACIEJEWSKI, JP KATEVAS, P ANDERSON, S YOUNG, NS TI PHENOTYPIC ANALYSIS OF BONE-MARROW IN APLASTIC-ANEMIA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A90 EP A90 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200345 ER PT J AU MACKALL, CL FLEISCHER, TA BROWN, MR MAGRATH, IT WEXLER, LH SHAD, AT GRESS, RE AF MACKALL, CL FLEISCHER, TA BROWN, MR MAGRATH, IT WEXLER, LH SHAD, AT GRESS, RE TI AGE-DEPENDENT DIFFERENCES IN CD4+ T-CELL REGENERATION ARE ASSOCIATED WITH INCREASED THYMOPOIESIS IN YOUNGER VS OLDER PATIENTS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A243 EP A243 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200958 ER PT J AU MCCLOSKEY, RP PIERCE, J KOSKI, R VARNUM, B LIU, E AF MCCLOSKEY, RP PIERCE, J KOSKI, R VARNUM, B LIU, E TI ACTIVATION OF THE AXL RECEPTOR TYROSINE KINASE INDUCES MITOGENESIS AND TRANSFORMATION IN 32D CELLS SO BLOOD LA English DT Meeting Abstract C1 UNIV N CAROLINA,CURRICULUM GENET,CHAPEL HILL,NC 27514. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. AMGEN CORP,THOUSAND OAKS,CA. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A183 EP A183 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200718 ER PT J AU MILLER, JL DONAHUE, RE WALSH, CW LIU, J SELLERS, SE SAMULSKI, RJ YOUNG, NS NIENHUIS, AW AF MILLER, JL DONAHUE, RE WALSH, CW LIU, J SELLERS, SE SAMULSKI, RJ YOUNG, NS NIENHUIS, AW TI EXPRESSION OF THE HUMAN GAMMA-GLOBIN GENE IN PURIFIED RHESUS HEMATOPOIETIC PROGENITOR CELLS TRANSDUCED WITH A RECOMBINANT ADENOASSOCIATED VIRUS (RAAV) VECTOR SO BLOOD LA English DT Meeting Abstract C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. UNIV N CAROLINA, CHAPEL HILL, NC 27514 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A434 EP A434 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201718 ER PT J AU OONISHI, T SAKASHITA, K SUEMATSU, N SCHECHTER, AN UYESAKA, N AF OONISHI, T SAKASHITA, K SUEMATSU, N SCHECHTER, AN UYESAKA, N TI SERUM-ALBUMIN PLAYS CRUCIAL ROLES TO COMPLETE P-GLYCOPROTEIN-MEDIATED EFFLUX SYSTEM IN ADRIAMYCIN-RESISTANT K562 CELLS SO BLOOD LA English DT Meeting Abstract C1 KANTO TEISHIN HOSP,DEPT PATHOL,TOKYO,JAPAN. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. NR 1 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A530 EP A530 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202103 ER PT J AU ORLIC, D BODINE, DM AF ORLIC, D BODINE, DM TI RT-PCR ANALYSIS OF GENE-EXPRESSION FOR GROWTH-FACTOR RECEPTORS AND TRANSCRIPTION FACTORS IN PURIFIED STEM-CELLS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A373 EP A373 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201473 ER PT J AU PETERS, B FIBACH, E DINH, K SCHECHTER, AN NOGUCHI, CT AF PETERS, B FIBACH, E DINH, K SCHECHTER, AN NOGUCHI, CT TI AN ERYTHROID-SPECIFIC FACTOR MAY MEDIATE THE NEGATIVE EFFECT OF THE EPSILON-GLOBIN SILENCER MOTIF WITH TRANSCRIPTION FACTOR-YY1 SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 1 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A219 EP A219 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200860 ER PT J AU RAGNI, M AMATO, D LOFARO, M KORVICK, J MERIGAN, T AF RAGNI, M AMATO, D LOFARO, M KORVICK, J MERIGAN, T TI CD(4) RESPONSE TO ANTIVIRAL THERAPY IN HIV(+) HEMOPHILIC MEN SO BLOOD LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NIAID,ROCKVILLE,MD. STATE UNIV GHENT,B-9000 GHENT,BELGIUM. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A413 EP A413 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201636 ER PT J AU RAMBALDI, A DIBERARDINO, C GAROFANO, A MOTTA, T GIUDICI, G GALLI, M CASLINI, C MAYO, JG BARBUI, T BIONDI, A GIAVAZZI, R AF RAMBALDI, A DIBERARDINO, C GAROFANO, A MOTTA, T GIUDICI, G GALLI, M CASLINI, C MAYO, JG BARBUI, T BIONDI, A GIAVAZZI, R TI IN-VIVO RELEASE OF HUMAN IL-1-BETA BY HUMAN ACUTE MYELOGENOUS LEUKEMIAS GROWING IN SCID MICE SO BLOOD LA English DT Meeting Abstract C1 OSPED RIUNITI BERGAMO,DIV EMATOL & ANAT PATOL,BERGAMO,ITALY. UNIV MILAN,PEDIAT CLIN,I-20122 MILAN,ITALY. NCI,BETHESDA,MD 20892. RI Caslini, Corrado/A-1689-2012 OI Caslini, Corrado/0000-0001-8326-8368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A545 EP A545 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202163 ER PT J AU RAO, C JOHNSON, J LALITHA, N BHATIA, K OCONOR, G MAGRATH, IT AF RAO, C JOHNSON, J LALITHA, N BHATIA, K OCONOR, G MAGRATH, IT TI PRESENCE OF EPSTEIN-BARR-VIRUS (EBV) AND OVEREXPRESSION OF P53 IN HODGKINS-DISEASE SO BLOOD LA English DT Meeting Abstract C1 KIDWAI MEM INST ONCOL,BANGALORE,INDIA. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A385 EP A385 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201522 ER PT J AU SAMANIEGO, F GALLO, RC ENSOLI, B AF SAMANIEGO, F GALLO, RC ENSOLI, B TI INFLAMMATORY CYTOKINES STIMULATE THE RELEASE OF BASIC FIBROBLAST GROWTH-FACTOR BY AIDS-KAPOSIS SARCOMA-DERIVED CELLS SO BLOOD LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A626 EP A626 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202485 ER PT J AU SANTUCCI, MA RAMPONI, GP RUGGIERO, M PACINI, S MINIACI, G BARBIERI, E PIERCE, JH GREENBERGER, JS AF SANTUCCI, MA RAMPONI, GP RUGGIERO, M PACINI, S MINIACI, G BARBIERI, E PIERCE, JH GREENBERGER, JS TI OVEREXPRESSION OF A SYNTHETIC PHOSPHOTYROSINE PROTEIN PHOSPHATASE GENE INCREASES RADIOSENSITIVITY IN-VITRO OF NORMAL AND TRANSFORMED FIBROBLASTS SO BLOOD LA English DT Meeting Abstract C1 UNIV PITTSBURGH,SCH MED,DEPT RADIAT ONCOL,PITTSBURGH,PA 15261. NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A533 EP A533 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202113 ER PT J AU SANTUCCI, MA PIERCE, JH FREZZA, G BABINI, L GREENBERGER, JS AF SANTUCCI, MA PIERCE, JH FREZZA, G BABINI, L GREENBERGER, JS TI ERYTHROPOIETIN ACTS AS A RADIOPROTECTOR OF PURE HEMATOPOIETIC PROGENITOR CELLS EXPRESSING THE COGNATE RECEPTOR SO BLOOD LA English DT Meeting Abstract C1 UNIV PITTSBURGH,SCH MED,DEPT RADIAT ONCOL,PITTSBURGH,PA 15261. NCI,MOLEC & CELL BIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A226 EP A226 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200890 ER PT J AU SCHWARTZ, GN WARREN, MK KESSLER, SW DE, M SZABO, JM PERDUE, JF AF SCHWARTZ, GN WARREN, MK KESSLER, SW DE, M SZABO, JM PERDUE, JF TI INSULIN-LIKE GROWTH FACTOR-II (IGF-II) ENHANCED CYTOKINE-INDUCED PROLIFERATION AND DIFFERENTIATION OF MYELOID AND MEGAKARYOCYTE PROGENITOR CELLS IN SERUM-DEPRIVED LIQUID CULTURES OF CD34+ BONE-MARROW CELLS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20814. AMER PHARM INC,ROCKVILLE,MD. AMER RED CROSS,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A103 EP A103 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200395 ER PT J AU SEKHSARIA, S SHALIT, M BROWN, MR FLEISHER, T MALECH, HL AF SEKHSARIA, S SHALIT, M BROWN, MR FLEISHER, T MALECH, HL TI CHARACTERIZATION OF SURFACE-ANTIGEN HETEROGENEITY OF HUMAN PERIPHERAL-BLOOD CD34+ CELLS OBTAINED FROM NORMAL DONORS SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIH,CTR CLIN,IMMUNOL SERV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A490 EP A490 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201944 ER PT J AU SHAD, A BHATIA, K HAMDY, N MUELLER, B PIZZO, P PENG, JW KNUTSEN, T JAFFE, E MAGRATH, I AF SHAD, A BHATIA, K HAMDY, N MUELLER, B PIZZO, P PENG, JW KNUTSEN, T JAFFE, E MAGRATH, I TI MOLECULAR CHARACTERIZATION OF PEDIATRIC HIV-ASSOCIATED NON-HODGKINS-LYMPHOMAS SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,DEPT PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A578 EP A578 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202296 ER PT J AU SHAD, A ADDE, M MAGRATH, I AF SHAD, A ADDE, M MAGRATH, I TI RESULTS OF NCI PROTOCOL 77-04 FOR TREATMENT OF LYMPHOBLASTIC LYMPHOMA IN CHILDREN SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A387 EP A387 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201532 ER PT J AU SHULMAN, NR JONES, CE REID, DM HE, RY AF SHULMAN, NR JONES, CE REID, DM HE, RY TI EVIDENCE THAT DRUG, NOT A NEOANTIGEN, IS THE PRIMARY DETERMINANT OF DRUG-DEPENDENT ANTIBODY REACTIONS SO BLOOD LA English DT Meeting Abstract C1 NIH,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A268 EP A268 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201056 ER PT J AU SIDRANSKY, E MARTIN, BM ELIASON, W GALDZICKA, M FISHERMAN, J CHO, M LEE, C GILBERT, C SHORR, R GINNS, EI AF SIDRANSKY, E MARTIN, BM ELIASON, W GALDZICKA, M FISHERMAN, J CHO, M LEE, C GILBERT, C SHORR, R GINNS, EI TI PRECLINICAL STUDIES WITH POLYETHYLENE-GLYCOL MODIFIED GLUCOCEREBROSIDASE AS A POTENTIAL THERAPY FOR GAUCHER PATIENTS SO BLOOD LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. ENZON INC,DEPT RES & DEV,PISCATAWAY,NJ. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A513 EP A513 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202034 ER PT J AU SLOAND, E PIERCE, P TUERNER, J KLEIN, HG AF SLOAND, E PIERCE, P TUERNER, J KLEIN, HG TI VANCOMYCIN INHIBITS BACTERIAL-GROWTH IN PLATELET CONCENTRATE (PCS) WHILE MAINTAINING PLATELET INTEGRITY AND FUNCTION SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A401 EP A401 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201585 ER PT J AU SLOAND, EM KLEIN, HG ALYONO, D AF SLOAND, EM KLEIN, HG ALYONO, D TI FLOW CYTOMETRIC EVALUATION OF PLATELET MEMBRANE-GLYCOPROTEINS (PMG) IN BLOOD OBTAINED FROM UNWASHED INTRAOPERATIVE SALVAGE DEVICE (IOSD) FOLLOWING CARDIOPULMONARY BYPASS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A337 EP A337 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201331 ER PT J AU SMITH, DA FEUERSTEIN, IM ROSENFELD, SJ KIMBALL, J YOUNG, NS AF SMITH, DA FEUERSTEIN, IM ROSENFELD, SJ KIMBALL, J YOUNG, NS TI BONE-MARROW MRI IN PATIENTS WITH APLASTIC-ANEMIA DOES NOT PREDICT EVOLUTION TO CLONAL DISEASE SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A90 EP A90 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200346 ER PT J AU SORRENTINO, BP MCDONAGH, KT ORLIC, D AF SORRENTINO, BP MCDONAGH, KT ORLIC, D TI P-GLYCOPROTEIN MESSENGER-RNA LEVELS IN MURINE HEMATOPOIETIC-CELLS TRANSDUCED WITH RETROVIRAL VECTORS EXPRESSING THE HUMAN MULTIDRUG RESISTANCE-1 CDNA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,CLIN IMMUNOL BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A216 EP A216 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200849 ER PT J AU SPIVAK, JL AVEDISSIAN, LS JENSEN, RA WILLIAMS, D HANKINS, WD PIERCE, J AF SPIVAK, JL AVEDISSIAN, LS JENSEN, RA WILLIAMS, D HANKINS, WD PIERCE, J TI ISOLATION OF THE FULL-LENGTH MURINE ERYTHROPOIETIN RECEPTOR (EPO-R) USING A BACULOVIRUS EXPRESSION SYSTEM SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DIV HEMATOL,BALTIMORE,MD 21205. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A228 EP A228 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200897 ER PT J AU STEINER, M LEE, ES NOGUCHI, CT ANAGNOSTOU, A AF STEINER, M LEE, ES NOGUCHI, CT ANAGNOSTOU, A TI THE ERYTHROPOIETIN-INDUCED PROLIFERATION OF HUMAN ENDOTHELIAL-CELLS IS ASSOCIATED WITH P34(CDC2) KINASE ACTIVATION SO BLOOD LA English DT Meeting Abstract C1 BROWN UNIV,SCH MED,DIV HEMATOL,PROVIDENCE,RI 02912. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A226 EP A226 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200888 ER PT J AU TANNENBAUM, S FRAKER, D ALEXANDER, HR ARNOLD, WS MERRYMAN, P GRALNICK, H AF TANNENBAUM, S FRAKER, D ALEXANDER, HR ARNOLD, WS MERRYMAN, P GRALNICK, H TI ACTIVATION OF COAGULATION BY TNF IN ISOLATED LIMB LIVER PERFUSIONS SO BLOOD LA English DT Meeting Abstract C1 NCI,HEMATOL SECT,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A282 EP A282 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201111 ER PT J AU TANNENBAUM, S CHAO, E GRALNICK, H AF TANNENBAUM, S CHAO, E GRALNICK, H TI THE QUANTITATION OF ENDOTHELIAL-CELL VWF AS AN INDICATOR OF ANGIOGENESIS SO BLOOD LA English DT Meeting Abstract C1 NIH,HEMATOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A149 EP A149 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200580 ER PT J AU UYESAKA, N HASEGAWA, S NAKAMURA, T HONGO, AT SCHECHTER, AN SHIO, H AF UYESAKA, N HASEGAWA, S NAKAMURA, T HONGO, AT SCHECHTER, AN SHIO, H TI PATHOPHYSIOLOGIC SIGNIFICANCE OF MECHANICAL FRAGILITY OF RED-BLOOD-CELLS SO BLOOD LA English DT Meeting Abstract C1 NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. NIDDK,CHEM BIOL LAB,BETHESDA,MD. SHIGA MED CTR ADULT DIS,SHIGA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A460 EP A460 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201824 ER PT J AU VANDENDRIESSCHE, T CHUAH, M NEWMAN, K MULLEN, C MORGAN, R AF VANDENDRIESSCHE, T CHUAH, M NEWMAN, K MULLEN, C MORGAN, R TI DEVELOPMENT AND ANALYSIS OF RETROVIRAL VECTORS EXPRESSING HUMAN FACTOR-VIII AND FACTOR-IX AS A POTENTIAL GENE-THERAPY FOR HEMOPHILIA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A67 EP A67 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200255 ER PT J AU VESOLE, D KORNBLUTH, J JAGANNATH, S SZNOL, M MATTOX, S VAUGHT, L TRICOT, G BARLOGIE, B AF VESOLE, D KORNBLUTH, J JAGANNATH, S SZNOL, M MATTOX, S VAUGHT, L TRICOT, G BARLOGIE, B TI BIOLOGICAL RESPONSE MODIFIERS (BRM)IN REFRACTORY MULTIPLE-MYELOMA (MM) - LACK OF CLINICAL EFFICACY OF RECOMBINANT HUMAN INTERLEUKIN-4 (RHIL-4) AND ALL-TRANS-RETINOIC ACID (ATRA) SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS,LITTLE ROCK,AR 72204. NCI,BETHESDA,MD 20892. NR 0 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A263 EP A263 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201036 ER PT J AU WALSH, CE NIENHUIS, AW SAMULSKI, RJ MILLER, JL YOUNG, NS LIU, JM AF WALSH, CE NIENHUIS, AW SAMULSKI, RJ MILLER, JL YOUNG, NS LIU, JM TI PHENOTYPIC CORRECTION OF FANCONI-ANEMIA (FACC) IN LYMPHOBLASTS AND CD34+ PROGENITORS WITH A RECOMBINANT ADENOASSOCIATED VIRUS (RAAV) VECTOR SO BLOOD LA English DT Meeting Abstract C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. UNIV N CAROLINA, CHAPEL HILL, NC 27514 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A347 EP A347 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201372 ER PT J AU WALSH, CE GROMPE, M YOUNG, NS NIENHUIS, AW LIU, JM AF WALSH, CE GROMPE, M YOUNG, NS NIENHUIS, AW LIU, JM TI A FUNCTIONALLY ACTIVE RETROVIRUS VECTOR FOR GENE-THERAPY IN FANCONIS ANEMIA TYPE-C SO BLOOD LA English DT Meeting Abstract C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A176 EP A176 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200690 ER PT J AU WANG, ZX WASNIOWSKA, K CHITNIS, C MILLER, LH HADLEY, TJ PEIPER, SC AF WANG, ZX WASNIOWSKA, K CHITNIS, C MILLER, LH HADLEY, TJ PEIPER, SC TI EXPRESSION OF THE EXTRACELLULAR DOMAIN OF THE PLASMODIUM-VIVAX RECEPTOR FOR THE HUMAN DUFFY RED-CELL ANTIGEN IN BACULOVIRUS SO BLOOD LA English DT Meeting Abstract C1 UNIV LOUISVILLE,JAMES GRAHAM BROWN CANC CTR,LOUISVILLE,KY 40292. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A267 EP A267 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201051 ER PT J AU WEINTRAUB, M BHATIA, K SPANGLER, G MAGRATH, IT AF WEINTRAUB, M BHATIA, K SPANGLER, G MAGRATH, IT TI EBV ASSOCIATED DIFFERENTIAL EXPRESSION OF GENES IN BURKITTS-LYMPHOMA SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A535 EP A535 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68202122 ER PT J AU WHANGPENG, J RAFFELD, M KNUTSEN, T YANO, T ZHAO, WP YARCHOAN, R PLUDA, JM KAUFMAN, D JAFFE, E AF WHANGPENG, J RAFFELD, M KNUTSEN, T YANO, T ZHAO, WP YARCHOAN, R PLUDA, JM KAUFMAN, D JAFFE, E TI HIV-ASSOCIATED LYMHPOMA - CYTOGENETIC AND MOLECULAR STUDIES SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,DEPT PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A385 EP A385 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201523 ER PT J AU XU, LC BLANCO, M STAHL, SK KESSLER, S DUNBAR, C KARLSSON, S AF XU, LC BLANCO, M STAHL, SK KESSLER, S DUNBAR, C KARLSSON, S TI CORRECTION OF THE ENZYME DEFICIENCY IN HEMATOPOIETIC-CELLS OF GAUCHER PATIENTS USING A CLINICALLY ACCEPTABLE RETROVIRAL SUPERNATANT TRANSDUCTION PROTOCOL SO BLOOD LA English DT Meeting Abstract C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A217 EP A217 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200852 ER PT J AU YANG, YP VANIN, EF BROSCIUS, C SCHNEIDERMAN, R NIENHUIS, AW AF YANG, YP VANIN, EF BROSCIUS, C SCHNEIDERMAN, R NIENHUIS, AW TI DEVELOPMENT AND CHARACTERIZATION OF A PACKAGING CELL-LINE THAT GENERATES NOVEL RETROVIRAL VECTORS WITH BROAD MAMMALIAN HOST-CELL RANGE SO BLOOD LA English DT Meeting Abstract C1 NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DIV EXPTL HEMATOL, MEMPHIS, TN 38101 USA. GENET THERAPY INC, GAITHERSBURG, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A300 EP A300 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201184 ER PT J AU YANO, T CLARK, HM SANDER, CA DOLEZAL, MV SHIBATA, D JAFFE, ES RAFFELD, M AF YANO, T CLARK, HM SANDER, CA DOLEZAL, MV SHIBATA, D JAFFE, ES RAFFELD, M TI CLUSTERED MUTATIONS IN THE 2ND EXON OF THE MYC GENE IN AGGRESSIVE LYMPHOMAS CARRYING MYC TRANSLOCATION SO BLOOD LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV SO CALIF,PATHOL LAB,LOS ANGELES,CA 90089. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A48 EP A48 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68200178 ER PT J AU YU, M SLOAND, EM KLEIN, HG AF YU, M SLOAND, EM KLEIN, HG TI COMPARISON OF PLATELET CONCENTRATES PREPARED FROM RED-CELL UNITS WITH PLATELETS FROM APHERESIS COLLECTIONS SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1993 VL 82 IS 10 SU 1 BP A399 EP A399 PG 1 WC Hematology SC Hematology GA MJ682 UT WOS:A1993MJ68201577 ER PT J AU BURKE, HB HENSON, DE AF BURKE, HB HENSON, DE TI CRITERIA FOR PROGNOSTIC FACTORS AND FOR AN ENHANCED PROGNOSTIC SYSTEM SO CANCER LA English DT Article DE PROGNOSTIC FACTORS; STAGING; TNM; PROGNOSTIC INDEX; PROGNOSIS; OUTCOME; BREAST CANCER; AMERICAN-JOINT-COMMITTEE-ON-CANCER ID NEGATIVE BREAST-CANCER; STAGE; CARCINOMA; SURVIVAL; INDEX; INDICATORS; EXPRESSION; DIAGNOSIS; RECEPTORS; ESTROGEN AB The American Joint Committee on Cancer proposes the following criteria for evaluating putative prognostic factors: they must be (1) significant, (2) independent, and (3) clinically important. Furthermore, we suggest the criteria for selecting a prognostic system that includes TNM and new prognostic factors. These criteria are: (1) easy for physicians to use; (2) provides predictions for all types of cancer; (3) provides the most accurate relapse and survival predictions at diagnosis and for every year lived for each patient; (4) provides group survival curves, where the grouping can be by any variable including outcome and therapy; (5) accommodates missing data and censored patients and is tolerant of noisy and biased data; (6) makes no a priori assumptions regarding the type of data, the distribution of the variables, or the relationships among the variables; (7) can test putative prognostic factors for significance, independence, and clinical importance; (8) accommodates treatment information in the evaluation of prognostic factors; (9) accommodates new putative prognostic factors without changing the model; (10) accommodates emerging diagnostic techniques; (11) provides information regarding the importance of each predictive variable; and (12) is automatic. C1 UNIV NEVADA,CTR BIOMED MODELING RES,RENO,NV 89557. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP BURKE, HB (reprint author), UNIV NEVADA,SCH MED,DEPT MED,WASHOE MED CTR,77 PRINGLE WAY,RENO,NV 89520, USA. NR 41 TC 87 Z9 88 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 NOV 15 PY 1993 VL 72 IS 10 BP 3131 EP 3135 DI 10.1002/1097-0142(19931115)72:10<3131::AID-CNCR2820721039>3.0.CO;2-J PG 5 WC Oncology SC Oncology GA MF581 UT WOS:A1993MF58100038 PM 8221580 ER PT J AU RONG, S JEFFERS, M RESAU, JH TSARFATY, I OSKARSSON, M VANDEWOUDE, GF AF RONG, S JEFFERS, M RESAU, JH TSARFATY, I OSKARSSON, M VANDEWOUDE, GF TI MET EXPRESSION AND SARCOMA TUMORIGENICITY SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; KINASE-ACTIVITY; PROTOONCOGENE; FIBROBLASTS; RECEPTOR; ACTIVATION; CELLS; AMPLIFICATION; MECHANISM AB The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563-569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 30 TC 145 Z9 146 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1993 VL 53 IS 22 BP 5355 EP 5360 PG 6 WC Oncology SC Oncology GA MF513 UT WOS:A1993MF51300004 PM 7693339 ER PT J AU EVANS, MK TAFFE, BG HARRIS, CC BOHR, VA AF EVANS, MK TAFFE, BG HARRIS, CC BOHR, VA TI DNA STRAND BIAS IN THE REPAIR OF THE P53 GENE IN NORMAL HUMAN AND XERODERMA-PIGMENTOSUM GROUP-C FIBROBLASTS SO CANCER RESEARCH LA English DT Article ID HUMAN CANCERS; ACTIVE GENE; WILD-TYPE; MUTATIONS; CELLS; CARCINOMAS; DEFICIENT; PROTEIN; TUMORS; DAMAGE AB We have measured the gene-specific and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in the p53 tumor suppressor gene in a normal, repair-proficient human fibroblast strain and in fibroblasts from a patient with the repair deficient disorder xeroderma pigmentosum, complementation xeroderma pigmentosum group C (XP-C). In both cell strains, repair was measured in the p53 gene and in its individual DNA strands. For comparison, the repair also was measured in other genomic regions in these human fibroblast strains, including the housekeeping gene dihydrofolate reductase, and two inactive genomic regions, the delta globin gene, and the 754 locus of the X chromosome. In both cell strains, we find that the p53 gene is repaired faster than the dihydrofolate reductase gene and much more efficiently than the inactive genomic regions. Selective repair of the transcribed DNA strand of p53 is observed in both human cell strains; the strand bias of repair is particularly distinct in XP-C. Mutations specific to the nontranscribed strand may occur due to replication errors at the sites of unrepaired DNA damage. Therefore, our results predict that the majority of mutations in skin cancers, especially those from patients with XP-C, would occur on the nontranscribed strand of the p53 gene. Indeed, Dumasz et al. (Proc. Natl. Acad. Sci. USA, in press, 1993) report such a strand bias of p53 mutation in skin cancers from XP-C patients. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP EVANS, MK (reprint author), NIA,MOLEC GENET LAB,BALTIMORE,MD 21224, USA. NR 35 TC 69 Z9 69 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1993 VL 53 IS 22 BP 5377 EP 5381 PG 5 WC Oncology SC Oncology GA MF513 UT WOS:A1993MF51300009 PM 8221675 ER PT J AU ESHERICK, JS DICUNTO, F FLANDERS, KC MISSERO, C DOTTO, GP AF ESHERICK, JS DICUNTO, F FLANDERS, KC MISSERO, C DOTTO, GP TI TRANSFORMING GROWTH FACTOR-BETA(1) INDUCTION IS ASSOCIATED WITH TRANSFORMING GROWTH FACTOR-BETA(2) AND FACTOR-BETA(3) DOWN-MODULATION IN 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED SKIN HYPERPLASIA SO CANCER RESEARCH LA English DT Article ID FACTOR-BETA; MESSENGER-RNA; EXPRESSION PATTERNS; COMPLEX REGULATION; MOUSE EPIDERMIS; RETINOIC ACID; TGF BETA-1; LOCALIZATION; KERATINOCYTES; FIBROBLASTS AB Acute treatment of mouse skin with the tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) induces marked epidermal hyperplasia, which is well evident by 24 h and maximal by 48-72 h. These effects are associated with the early induction of transforming growth factor (TGF) beta1 expression in the epidermis. We show here that, in contrast to TGF-beta1, TGF-beta2, and TGF-beta3, skin expression is significantly down-modulated in response to TPA. TGF-beta3 RNA levels decreased by 6 h of treatment but returned to normal or even higher levels at later times. The TGF-beta3 protein could be detected immunohistochemically in both dermis and epidermis in control skins and at early times of TPA treatment. However, at later times, TGF-beta3 was found only in dermal cells and not in the epidermis. TGF-beta2 RNA expression was found to be significantly down-modulated by 24 h of TPA treatment and remained low even at later times. Thus, differential control of the 3 TGF-beta isoforms appears to be a likely determinant of normal skin homeostasis and could be at least partially responsible for TPA-induced skin hyperplasia. C1 YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 36 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1993 VL 53 IS 22 BP 5517 EP 5522 PG 6 WC Oncology SC Oncology GA MF513 UT WOS:A1993MF51300033 ER PT J AU PAUL, IA LAYER, RT SKOLNICK, P NOWAK, G AF PAUL, IA LAYER, RT SKOLNICK, P NOWAK, G TI ADAPTATION OF THE NMDA RECEPTOR IN RAT CORTEX FOLLOWING CHRONIC ELECTROCONVULSIVE SHOCK OR IMIPRAMINE SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE ELECTROCONVULSIVE SHOCK; IMIPRAMINE; NMDA (N-METHYL-D-ASPARTATE) RECEPTOR COMPLEX; STRYCHNINE-INSENSITIVE GLYCINE RECEPTOR; 5,7-DICHLOROKYNURENIC ACID; CGP-39653 ID FORCED SWIM TEST; ANTIDEPRESSANT DRUGS; BINDING-SITES; EXHIBIT ANTIDEPRESSANT; NEURAL ADAPTATION; CEREBRAL-CORTEX; DOWN-REGULATION; D-SERINE; MODULATION; GLYCINE AB Chronic (14 days) administration of either imipramine or electroconvulsive shock effected significant changes in the ligand binding properties of the NMDA (N-methyl-D-aspartate) receptor complex in rat cortex. These changes were manifested as: (1) a reduction in the potency of glycine to inhibit the binding of 5,7-dichloro[H-3]kynurenic acid to strychnine-insensitive glycine receptors; and (2) a reduction in the proportion of high affinity, glycine-displaceable [H-3]CGP-39653 binding to NMDA receptors. Chronic electroconvulsive shock, but not imipramine treatment also reduced the density of [H-3]CGP-39653 binding sites in cortical membranes. These findings demonstrate that the ability of chronic antidepressant treatments to induce adaptive changes in the glycine and glutamate regulatory sites of the NMDA receptor is not species specific, since it obtains in rats as well as mice. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NR 33 TC 83 Z9 85 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD NOV 15 PY 1993 VL 247 IS 3 BP 305 EP 311 DI 10.1016/0922-4106(93)90199-J PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH409 UT WOS:A1993MH40900011 PM 7905831 ER PT J AU ABE, T KIKUCHI, T CHANG, T SHINOHARA, T AF ABE, T KIKUCHI, T CHANG, T SHINOHARA, T TI THE SEQUENCE OF THE MOUSE PHOSDUCIN-ENCODING GENE AND ITS 5'-FLANKING REGION SO GENE LA English DT Article DE RECOMBINANT DNA; INTRONS; EXONS; PHOTOTRANSDUCTION ID RETINOID-BINDING PROTEIN; ROD OUTER SEGMENTS; S-ANTIGEN GENE; PINEAL-GLAND; TRANSGENIC MICE; CDNA; KINASE; PHOSPHOPROTEIN; EXPRESSION; PROMOTER AB Phosducin (Pd), a principal protein of retinal photoreceptor cells, modulates the phototransduction cascade by interacting with transducin. A recent report indicated that Pd and the G-protein-inhibitor protein (GIP) in brain are virtually identical. Here, we have sequenced the complete mouse clone (P1-AT) carrying the Pd gene, 3026 bp of its 5'-flanking region, and cDNAs generated from the retinal mRNAs. Gene Pd is 15 kb in length and has four exons. The splice sites for donor and acceptor were in good agreement with the GT/AG rule. Deduced Pd amino acid sequences were highly homologous to those of human, bovine and rat. In addition, we found more than one similar Pd gene and two different mRNAs. The P1-AT clone encodes one of the Pd mRNAs. These results open the possibility that the multiple Pd genes encode multiple Pd. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 327,BETHESDA,MD 20892. STANFORD UNIV,STANFORD,CA 94305. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 32 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 179 EP 186 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900004 PM 8224906 ER PT J AU CHERNAK, JM AF CHERNAK, JM TI STRUCTURAL FEATURES OF THE 5' UPSTREAM REGULATORY REGION OF THE GENE ENCODING RAT AMYLOID PRECURSOR PROTEIN SO GENE LA English DT Note DE APP PROMOTER; TRANSCRIPTIONAL REGULATION; GC BOXES; MOUSE; HUMAN; ALZHEIMERS DISEASE; DOWNS SYNDROME; AMYLOID PLAQUES; AGING ID ALZHEIMERS-DISEASE; TRANSCRIPTION INVITRO; MESSENGER-RNA; EXPRESSION; PROMOTER; SV40; APP; SEQUENCES; ELEMENTS; PATTERN AB The 5' upstream regulatory region of the gene encoding the rat amyloid precursor protein (APP) was cloned and sequenced. It lacks both a TATA box and a CAAT box, has a high G+C content (68%), is 89% homologous to the corresponding region of the mouse APP gene, and 82% homologous to the corresponding region of the human APP gene. This region contains putative regulatory elements both 5' and 3' to the probable transcription start point (tsp). There are consensus DNA sites for the binding of SP1, AP2, AP4 and GC factor (GCF) proteins, and two GC boxes with the consensus sequence, 5'-GGGYGCRG. Potential regulatory sites with only a single mismatch to the consensus sequences include three SP1, one AP1, five AP2, and two GCF sites, as well as one GC box. There are also six potential stem-loop secondary structures (SSS) near the probable tsp. A consecutive series of elements, consisting of a GC box, AP2 site, three SSS, two SP1 sites, and AP4, AP1 and GCF sites just upstream from the probable tsp, are well-conserved between the rat, mouse and human sequences. An additional AP2 site, two GC boxes, and two additional SSS appear to be conserved between species. However, two possible rat SP1 sites, three possible rat AP2 sites, and two possible rat GCF sites are lacking in the human. On the other hand, the rat sequence is missing four potential SP1 sites, four potential AP2 sites, and nine potential GC boxes which are found in the human sequence. Therefore, while all species contain a large variety of potential regulatory elements, the numbers and locations of these elements vary significantly from species to species. These differences may be functionally related to the appearance of amyloid plaques in older humans and Alzheimer's patients, but not in older or memory-impaired rodents. RP CHERNAK, JM (reprint author), NIA,MOLEC NEUROBIOL UNIT,ROOM 1B12,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 24 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 255 EP 260 DI 10.1016/0378-1119(93)90648-M PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900016 PM 8224912 ER PT J AU THAYER, RE SINGER, MF FANNING, TG AF THAYER, RE SINGER, MF FANNING, TG TI UNDERMETHYLATION OF SPECIFIC LINE-1 SEQUENCES IN HUMAN-CELLS PRODUCING A LINE-1-ENCODED PROTEIN SO GENE LA English DT Note DE RETROTRANSPOSON; METHYLCYTOSINE; GENE EXPRESSION ID DNA METHYLATION; IDENTIFICATION; TRANSCRIPTION; EXPRESSION; PROMOTER; ISLANDS; BINDING; ELEMENT; END AB Nucleotide sequences near the 5' ends of some long interspersed elements-1 (LINE-1) from Homo sapiens (L1Hs) are undermethylated in cell lines which produce a L1Hs-encoded protein. In contrast, these sequences are methylated in cell lines with little or no detectable L1Hs expression. The fact that the 5' end of L1Hs is differentially methylated in cells exhibiting different levels of L1Hs expression suggests that the methylation state of this region plays a role in L1Hs expression. C1 ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 23 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 273 EP 277 DI 10.1016/0378-1119(93)90651-I PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900019 PM 7693554 ER PT J AU MURPHY, PM TIFFANY, HL MCDERMOTT, D AHUJA, SK AF MURPHY, PM TIFFANY, HL MCDERMOTT, D AHUJA, SK TI SEQUENCE AND ORGANIZATION OF THE HUMAN N-FORMYL PEPTIDE RECEPTOR-ENCODING GENE SO GENE LA English DT Note DE G-PROTEIN-COUPLED RECEPTOR; ALU REPEAT; INTRONLESS CODING REGION; CHEMOATTRACTANT RECEPTOR; MYELOID-SPECIFIC GENE ID EXPRESSION; LOCALIZATION; PROTEIN; CDNA AB The human FPR1 gene encodes the N-formyl peptide receptor, a G protein-coupled receptor (GPCR) that mediates the activation of mature myeloid cells by bacterial N-formyl oligopeptides. To investigate the molecular basis for myeloid-specific production of this receptor, we have cloned and sequenced FPR1. The gene is organized into three exons and two introns that span 6 kb. The coding block lacks introns. Yet, the transcription start point (tsp) is separated from the start codon by 4902 bp consisting of three exons and two large introns. Two mRNAs are produced by alternative splicing of exon 2 in HL-60 neutrophils and normal blood monocytes. The region 5' to the tsp contains three pyrimidine-rich segments, a feature that has been observed in other myeloid-specific genes. One complete Alu repeat is found in each intron and in the 3'-flanking region 317 bp downstream of the polyadenylation signal. Thus, FPR1 is a small myeloid-specific gene that is expressed as two alternatively spliced mRNAs encoding the same protein. RP MURPHY, PM (reprint author), NIAID,HOSP DEF LAB,BLDG 10,ROOM 11N113,BETHESDA,MD 20892, USA. OI McDermott, David/0000-0001-6978-0867 NR 22 TC 35 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 285 EP 290 DI 10.1016/0378-1119(93)90653-K PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900021 PM 8224916 ER PT J AU WANG, TTY LEWIS, KC PHANG, JM AF WANG, TTY LEWIS, KC PHANG, JM TI PRODUCTION OF HUMAN PLASMA RETINOL-BINDING PROTEIN IN ESCHERICHIA-COLI SO GENE LA English DT Note DE VITAMIN-A METABOLISM; RECOMBINANT DNA; PLASMA; PROTEIN PURIFICATION; NUTRIENT METABOLISM AB We designed a polymerase chain reaction (PCR) primer pair which allowed us to clone the cDNA coding for the human plasma retinol-binding protein (hRBP) into an Escherichia coli expression vector. Production of hRBP was confirmed by probing Western blots with antisera against plasma hRBP. Purification and characterization of the E. coli-produced plasma hRBP are also described. The availability of this expression system makes it possible to obtain large quantities of hRBP to facilitate our continuing studies of retinol and RBP metabolism. RP WANG, TTY (reprint author), NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC REGULAT LAB,BLDG 434-2,POB B,FREDERICK,MD 21702, USA. NR 9 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 291 EP 294 DI 10.1016/0378-1119(93)90654-L PG 4 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900022 PM 8224917 ER PT J AU CHAMBERS, C RUSSELL, P AF CHAMBERS, C RUSSELL, P TI SEQUENCE OF THE HUMAN LENS BETA-B2-CRYSTALLIN-ENCODING CDNA SO GENE LA English DT Note DE RECOMBINANT DNA; STRUCTURAL PROTEIN; EYE; EYE CATARACT; POLYMERASE CHAIN REACTION; PROTEIN SIMILARITY ID CRYSTALLIN GENE FAMILY; HEREDITARY CATARACT; NUCLEOTIDE-SEQUENCE; EYE LENS; EVOLUTION; RAT; TRANSPARENCY; CONSERVATION; POLYPEPTIDE; EXPRESSION AB This study reports the nucleotide (nt) sequence of the human betaB2-crystallin (hbetaB2-Cry)-encoding cDNA (hbetaB2-cry). The hbetaB2-cry gene encodes a major structural protein in the lens of the vertebrate eye. Sequence information obtained from mouse genomic clones and the mouse betaB2-cry cDNA (mbetaB2-cry) sequence was used to design oligodeoxyribonucleotide primers, corresponding to exon 1, transcription start points, and termination and polyadenylation sites, that were used in the polymerase chain reaction (PCR) to generate full-length cDNA clones from total human lens RNA. In addition, cDNA libraries were made with lambdagt11 from both human fetal and adult lens tissue RNAs, and screened with a mbetaB2-cry cDNA clone. The full-length hbetaB2-cry cDNA is 721 bp and contains an open reading frame of 612 nt. It codes for a 23-kDa protein of 205 amino acid residues. Comparison of the overall nt and deduced aa sequences shows a greater similarity of hbetaB2-cry to bovine betaB2-cry than to mbetaB2-cry or rat betaB2-cry. RP CHAMBERS, C (reprint author), NEI,MECH OCULAR DIS LAB,CATARACTS SECT,BLDG 6,RM 228,BETHESDA,MD 20892, USA. NR 22 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1993 VL 133 IS 2 BP 295 EP 299 DI 10.1016/0378-1119(93)90655-M PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MH039 UT WOS:A1993MH03900023 PM 8224918 ER PT J AU JOHNSTONE, PA SINDELAR, WF AF JOHNSTONE, PA SINDELAR, WF TI PATTERNS OF DISEASE RECURRENCE FOLLOWING DEFINITIVE THERAPY OF ADENOCARCINOMA OF THE PANCREAS USING SURGERY AND ADJUVANT RADIOTHERAPY - CORRELATIONS OF A CLINICAL-TRIAL SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE PATTERNS OF FAILURE; PANCREATIC CANCER; INTRAOPERATIVE RADIOTHERAPY; RADIATION THERAPY; SURGERY ID CLINICOPATHOLOGIC CORRELATION; REOPERATION SERIES; RADIATION-THERAPY; CURATIVE SURGERY; FAILURE; AREAS; COLON AB Purpose: Between 1980 and 1984, 26 patients with resectable adenocarcinoma of the pancreatic head were enrolled in a National Cancer Institute protocol evaluating intraoperative radiotherapy vs. standard therapy. Methods and Materials: After complete excision of their lesions, patients were observed (Stage I), or randomized to intraoperative radiotherapy vs. external beam radiotherapy (Stages II-IV). The intraoperative dose was 20 Gy in a single fraction using 9-20 MeV electrons. The external beam radiotherapy schema involved daily 150-180 cGy fractions to 45-55 Gy in 5-6 weeks. Chemotherapy was not used for primary disease but was administered off protocol for recurrent disease. Median potential followup for the trial was > 9 years, with a median patient survival of 18 months. Perioperative mortality was 27% (7 patients). Of the remaining 19 patients, one remains alive and without evidence of disease 9 years post-therapy. Twelve patients underwent autopsy and 2 required antemortem laparotomy; histopathologic evidence of disease recurrence was analyzed. Results: Of 15 patients evaluable for intra-abdominal control, 7 (47%) suffered local recurrences and 7 (47%) failed regionally, with 5 patients (35%) failing in both areas. Five patients (35%) developed peritoneal seeding. Of 13 patients evaluable for systemic disease, 8 (62%) suffered distant failure. There were no differences in outcome between intraoperative or external beam radiotherapy or observation in this subset of patients. Conclusion: This report is among the most rigorous descriptions of patterns of failure after resection of pancreatic cancer. It appears clear that advances in local control of this disease are unlikely to translate into increased survival in the absence of improved systemic therapy. C1 NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DIV RADIAT ONCOL, BETHESDA, MD 20889 USA. NR 10 TC 47 Z9 47 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 1993 VL 27 IS 4 BP 831 EP 834 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA MH970 UT WOS:A1993MH97000010 PM 8244812 ER PT J AU PRASAD, K BAROUCH, W GREENE, L EISENBERG, E AF PRASAD, K BAROUCH, W GREENE, L EISENBERG, E TI A PROTEIN COFACTOR IS REQUIRED FOR UNCOATING OF CLATHRIN BASKETS BY UNCOATING ATPASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID COATED VESICLES; HEAT-SHOCK; ASSEMBLY PROTEINS; STRESS PROTEINS; PURIFICATION; DISSOCIATION; TRANSLOCATION; POLYPEPTIDES; BINDING; HSP70 AB Immediately after clathrin-coated pits pinch off from the cell membrane to form clathrin-coated vesicles, clathrin dissociates from the vesicles. In vitro studies suggest that this dissociation is carried out by the uncoating ATPase, a constitutive member of the 70-kDa heat shock family. Aside from the requirement for ATP, nothing is known about the regulation of the uncoating process. We now show that clathrin baskets prepared from highly purified clathrin and AP2, the assembly protein associated with plasma membrane coated vesicles, cannot be uncoated by the bovine brain uncoating ATPase alone. A 100-kDa protein cofactor, which was isolated from coated vesicles, is essential for uncoating by the uncoating ATPase. This cofactor restores normal uncoating when present at a molar ratio of about 1 to 10 to clathrin and uncoating ATPase. RP PRASAD, K (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 23758 EP 23761 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400007 PM 8226905 ER PT J AU SCHAAPER, RM AF SCHAAPER, RM TI BASE SELECTION, PROOFREADING, AND MISMATCH REPAIR DURING DNA-REPLICATION IN ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID POLYMERASE-III HOLOENZYME; SPONTANEOUS MUTATION; EXONUCLEASE ACTIVITY; LACI GENE; MECHANISMS; FIDELITY; MUTD5; SPECIFICITY; MUTAGENESIS; INVITRO AB The accuracy by which organisms duplicate their DNA is of considerable interest. At least three mechanisms operate, serially, to secure high fidelity: base selection, exonucleolytic proofreading, and postreplicative mismatch correction. To obtain insights into the efficiency and specificity of these steps in the bacterium Escherichia coli, we have performed DNA sequence analysis of mutations occurring in the bacterial lacI gene in a series of strains genetically disabled in one or more of these error avoidance pathways. The base selection efficiency was estimated from mutagenesis occurring in a mutDmutL strain, which is deficient in both proofreading (mutD5) and mismatch repair (mutL). The proofreading efficiency was derived comparing the mutD5 mutL strain to the mismatch repair-deficient mutL strain. The efficiency of mismatch repair was derived comparing the mutL strain to the wild-type strain. The results show that base selection discriminates against errors by 200,000-2,000,000-fold, proofreading by 40-200-fold, and mismatch repair by 20-400-fold, each depending on the type of error. Base selection and proofreading act more strongly against transversions than transitions, whereas mismatch repair does the opposite. The data are based on 866 sequenced lacI mutations in a target that allows the scoring of at least 127 different mutations in 76 distinct DNA sequence contexts in vivo. They may therefore have general significance. RP SCHAAPER, RM (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 210 Z9 212 U1 3 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 23762 EP 23765 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400008 PM 8226906 ER PT J AU DEGTYAREV, MY SPIEGEL, AM JONES, TLZ AF DEGTYAREV, MY SPIEGEL, AM JONES, TLZ TI INCREASED PALMITOYLATION OF THE G(S) PROTEIN-ALPHA SUBUNIT AFTER ACTIVATION BY THE BETA-ADRENERGIC-RECEPTOR OR CHOLERA-TOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID BETA-2-ADRENERGIC RECEPTOR; GS; STIMULATION; ACYLATION; MEMBRANE; MUTATION; GTP; IDENTIFICATION; CELLS AB The alpha subunit of the heterotrimeric G(s) protein that couples the beta-adrenergic receptor to adenylyl cyclase undergoes post-translational palmitoylation. We examined the dynamics of this modification of alpha(s) by metabolic labeling of COS and S49 lymphoma cells under different conditions. The endogenous alpha(s) proteins were immunoprecipitated with a peptide-specific antibody, separated by SDS-polyacrylamide gel electrophoresis, and analyzed by fluorography and densitometry. A pulse-chase study of COS cells incubated with [H-3]palmitate or [S-35]methionine showed that for alpha(s) the palmitate turnover (t1/2 almost-equal-to 50 min) was significantly faster than the protein degradation. Treatment of cells with 10 muM isoproterenol, a beta-adrenergic receptor agonist, in the presence of [H-3]palmitate led to a rapid 4-10-fold increase in the palmitoylation of alpha(s). This increase in palmitoylation was concentration-dependent (EC50 almost-equal-to 0.9 muM) and blocked by the antagonist propranolol. The mutant alpha(s) proteins in the unc and H21a S49 cell lines did not show an increase in [H-3]palmitate incorporation with isoproterenol treatment. Cholera toxin treatment of COS cells increased the [H-3]palmitate incorporation into the alpha(s) subunits. These data indicate that palmitoylation of the alpha(s) subunit is dynamic and regulated by activation of the alpha(s) subunit. C1 NIDDK,MPB,BLDG 10,RM 8C-101,BETHESDA,MD 20892. NR 24 TC 160 Z9 160 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 23769 EP 23772 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400010 PM 8226908 ER PT J AU NEYROZ, P DESDOUITS, F BENFENATI, F KNUTSON, JR GREENGARD, P GIRAULT, JA AF NEYROZ, P DESDOUITS, F BENFENATI, F KNUTSON, JR GREENGARD, P GIRAULT, JA TI STUDY OF THE CONFORMATION OF DARPP-32, A DOPAMINE-REGULATED AND CAMP-REGULATED PHOSPHOPROTEIN, BY FLUORESCENCE SPECTROSCOPY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN PHOSPHATASE INHIBITOR-1; TIME-RESOLVED FLUORESCENCE; 3'-5'-MONOPHOSPHATE-REGULATED NEURONAL PHOSPHOPROTEIN; RABBIT SKELETAL-MUSCLE; CASEIN KINASE-II; GLYCOGEN-PHOSPHORYLASE; ALCOHOL-DEHYDROGENASE; DECAY; TRYPTOPHAN; CLONING AB DARPP-32 is a potent inhibitor of protein phosphatase 1 when it is phosphorylated on Thr34 by cAMP-dependent protein kinase. DARPP-32 is also phosphorylated on Ser45 and Ser102 by casein kinase II, resulting in a facilitation of phosphorylation by cAMP-dependent protein kinase. We have studied the conformation of recombinant rat DARPP-32 by steady-state and time-resolved fluorescence. The steady-state emission spectra and quenching of the intrinsic (Trp163) and extrinsic fluorescence (acrylodan or lucifer yellow linked to Cys72) were consistent with a complete exposure of these residues to the aqueous environment. The intrinsic fluorescence of DARPP-32 was resolved into three decay components with lifetimes of 1, 3.4, and 7 ns, with the intermediate lifetime component giving the major contribution. The ratio between the amplitudes associated with the short and long decay constants was decreased upon denaturation. The rotational behavior of DARPP-32 measured by anisotropy decay revealed that Trp163 is located in a highly flexible peptide chain, whereas Cys72 is embedded in a more rigid environment. Phosphorylation by cAMP-dependent protein kinase did not alter any of the fluorescence parameters, whereas only minor effects were associated with casein kinase II phosphorylation. These findings indicate that DARPP-32 contains at least two distinct domains and that phosphorylation has no dramatic effects on its conformation. C1 COLL FRANCE,CHAIR NEUROPHARMACOL,INSERM,U114,F-75231 PARIS 05,FRANCE. UNIV ROMA TOR VERGATA,DIPARTIMENTO MED SPERIMENTALE & SCI BIOCHIM,ROME,ITALY. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. ROCKEFELLER UNIV,MOLEC & CELLULAR NEUROSCI LAB,NEW YORK,NY 10021. RP NEYROZ, P (reprint author), UNIV BOLOGNA,DIPARTIMENTO BIOCHIM G MORUZZI,SEZ BIOCHIM FARMACEUT,I-40126 BOLOGNA,ITALY. RI Girault, Jean-Antoine/F-7518-2013 OI Girault, Jean-Antoine/0000-0002-7900-1705 NR 64 TC 15 Z9 15 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 24022 EP 24031 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400049 PM 8226946 ER PT J AU SHIMURA, H IKUYAMA, S SHIMURA, Y KOHN, LD AF SHIMURA, H IKUYAMA, S SHIMURA, Y KOHN, LD TI THE CAMP RESPONSE ELEMENT IN THE RAT THYROTROPIN RECEPTOR PROMOTER - REGULATION BY EACH DECANUCLEOTIDE OF A FLANKING TANDEM REPEAT USES DIFFERENT, ADDITIVE, AND NOVEL MECHANISMS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEIN; GROWTH FACTOR-I; C-MYC GENE; H-DNA; TRANSCRIPTIONAL SILENCER; 5'-FLANKING REGION; EXPRESSION; ENHANCER; CELLS; IDENTIFICATION AB A decanucleotide tandem repeat (TR) sequence, between -162 and -140 base pairs (bp) of the minimal thyrotropin receptor promoter, decreases gene expression by repressing constitutive enhancer activity of its cAMP response element (CRE). Each decanucleotide acts additively. CRE-binding proteins and liver or thyroid nuclear extracts footprint a region including the CRE and the 3' decanucleotide, -148 to -124 bp; nuclear proteins interacting with the 3' decanucleotide protect a smaller region, -148 to -135 bp. Separate groups of nuclear proteins interact with the CRE and the 3' decanucleotide; mutations of the CRE affect protein interactions with the 3' decanucleotide and the converse. Nuclear proteins bind to single- or double-stranded 3' decanucleotide DNA; those interacting with the CRE bind only double-stranded DNA. The repressor action of the 5' decanucleotide is associated with an interaction between the coding strand and a single-stranded binding protein in liver and thyroid nuclear extracts. The 5' decanucleotide is in a CT-rich region with Sl nuclease hypersensitivity, near perfect mirror images, and direct repeats. The data therefore indicate that each TR decanucleotide modulates CRE constitutive enhancer activity by different but additive mechanisms, competition versus interaction with a single-stranded binding protein, and each interacts with different nuclear proteins that are not thyroid-specific. The same region in the human thyrotropin receptor represses CRE constitutive enhancer activity by the same mechanisms, despite a nonidentical sequence and no overt TR. C1 NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. NR 46 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 24125 EP 24137 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400063 PM 8226959 ER PT J AU TAFURI, SR WOLFFE, AP AF TAFURI, SR WOLFFE, AP TI SELECTIVE RECRUITMENT OF MASKED MATERNAL MESSENGER-RNA FROM MESSENGER-RIBONUCLEOPROTEIN PARTICLES CONTAINING FRGY2 (MESSENGER RNP4) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS OOCYTE MATURATION; TRANSCRIPTION FACTOR; BINDING-PROTEINS; 5S RNA; TRANSLATIONAL CONTROL; ESCHERICHIA-COLI; CYTOPLASMIC POLYADENYLATION; GENE; IDENTIFICATION; ELEMENTS AB In Xenopus, the germ cell-specific Y-box (CTGATTGGCCAA) factor, FRGY2, facilitates in vitro transcription in egg extracts from oocyte-selective promoters containing a Y-box. This same factor is a major component of the messenger ribonucleoprotein (mRNP) storage particles of the oocyte. These particles store maternal mRNAs and inhibit their translation. FRGY2 is identical to mRNP4 and homologous to mRNP3, two previously described oocyte-specific mRNP proteins. We demonstrate that FRGY2 associates with a broad spectrum of mRNAs exhibiting no apparent sequence specificity. These interactions suggest that FRGY2 has a general role in packaging mRNA analogous to that of histone with DNA. All mRNAs examined that accumulate in oocytes appear within these mRNP storage particles, including messages coding for proteins such as FRGY2 and TFIIIA, which are translated in the oocyte. Moreover, we show that mRNAs that are translationally repressed in oocytes, such as messages coding for the proteins histone H1 and FRGY1, accumulate only within the particles. These mRNAs are subsequently recruited from the particles to the ribosomes and utilized for translation during embryogenesis prior to transcriptional activation of the zygotic genome. We propose that the assembly of mRNP storage particles represents a default state and that translational regulation is achieved via specific recruitment of the messages from the mRNP fraction to the ribosomes. C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM B1A-13,BETHESDA,MD 20892. NR 45 TC 97 Z9 97 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 24255 EP 24261 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400080 PM 8226972 ER PT J AU HOLLANDER, MC ALAMO, I JACKMAN, J WANG, MG MCBRIDE, OW FORNACE, AJ AF HOLLANDER, MC ALAMO, I JACKMAN, J WANG, MG MCBRIDE, OW FORNACE, AJ TI ANALYSIS OF THE MAMMALIAN GADD45 GENE AND ITS RESPONSE TO DNA-DAMAGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSITU HYBRIDIZATION; CHROMOSOMAL LOCALIZATION; CELLS; EXPRESSION; DIFFERENTIATION; SEQUENCE; PROTEIN; AGENTS; PROBE; STEP AB The gadd45 gene is transcriptionally activated through at least two different mechanisms; one following treatment with base-damaging agents such as methylmethane sulfonate and UV radiation and the other following ionizing radiation. To investigate the sequences involved in induction of gadd45 by agents producing high levels of base damage, the hamster, human, and mouse genes were sequenced. Comparison of these sequences revealed a high level of conservation between species of 1500 base pairs of the proximal promoter and 700 base pairs within the third intron. However, in the promoter regions, there was no conservation between species of any transcription factor binding sites known to confer DNA damage responsiveness. The promoter of the hamster gene was inducible by base-damaging agents in both rodent and human cell lines and the human gene was inducible in a rodent cell line. This indicates that both sequence elements in the gadd45 promoter and factors binding to these sites are conserved in mammalian cells. Deletion analysis of the hamster promoter did not reveal any specific sequence which conferred damage inducibility and the maximal response required a large portion of the promoter. The hamster promoter was not inducible by ionizing radiation, suggesting that sequences outside the promoter region used, such as a p53 binding site in the third intron, are necessary. The human GADD45 gene was mapped to chromosome 1p31.1-31.2. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP HOLLANDER, MC (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 28 TC 209 Z9 217 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 NOV 15 PY 1993 VL 268 IS 32 BP 24385 EP 24393 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400099 PM 8226988 ER PT J AU LADERMAN, KA DAVIS, BR KRUTZSCH, HC LEWIS, MS GRIKO, YV PRIVALOV, PL ANFINSEN, CB AF LADERMAN, KA DAVIS, BR KRUTZSCH, HC LEWIS, MS GRIKO, YV PRIVALOV, PL ANFINSEN, CB TI THE PURIFICATION AND CHARACTERIZATION OF AN EXTREMELY THERMOSTABLE ALPHA-AMYLASE FROM THE HYPERTHERMOPHILIC ARCHAEBACTERIUM PYROCOCCUS-FURIOSUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUBACTERIUM THERMOTOGA-MARITIMA; COMPLETE NUCLEOTIDE-SEQUENCE; THERMAL-STABILITY; AMYLOLYTIC ENZYME; GENE; PROTEINS; SUBTILIS AB The alpha-amylase from Pyrococcus furiosus, a hyperthermophilic archaebacterium, has been purified to homogeneity. The enzyme is a homodimer with a subunit molecular mass of 66 kDa. The isoelectric point is 4.3. The enzyme displays optimal activity, with substantial thermal stability, at 100-degrees-C, with the onset of activity at approximately 40-degrees-C. Unlike mesophilic alpha-amylases there is no dependence on Ca2+ for activity or thermostability. The enzyme displays a broad range of substrate specificity, with the capacity to hydrolyze carbohydrates as simple as maltotriose. No subtrate binding occurs below the temperature threshold of activity, and a decrease in K(m) accompanies an increase in temperature. Except for a decrease in Asp and an increase in Glu, the amino acid composition does not confirm previously defined trends in thermal adaption. Fourth derivative UV spectroscopy and intrinsic fluorescence measurements detected no temperature-dependent structural reorganization. Hydrogen exchange results indicate that the molecule is rigid, with only a slight increase in conformational flexibility at elevated temperature. Scanning microcalorimetry detected no considerable change in the heat capacity function, at the pH of optimal activity, within the temperature range in which activity is induced. The heat absorption peak due to denaturation, under these conditions, occurred within the temperature range of 90-120-degrees-C. When the pH was increased, a change in the shape of the heat absorption peak was observed, which when analyzed thermodynamically shows that the process of heat denaturation is complex and includes at least three stages, indicating that the protein structure consists of three domains. At temperatures below 90-degrees-C no excess heat absorption or change in the CD spectra were observed which could be associated with the cooperative conformational transition of the protein. According to the thermodynamic characteristics of the heat denaturation, the cold denaturation of this protein can be expected only at -3-degrees-C. Therefore, the observed inactivation of this enzyme is not caused by the cooperative change of its tertiary structure. It can be associated only with the gradual changes of protein domain interaction. C1 JOHNS HOPKINS UNIV,DEPT BIOL,34TH & CHARLES ST,BALTIMORE,MD 21218. NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 38 TC 112 Z9 117 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 24394 EP 24401 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400100 PM 8226989 ER PT J AU MITSUI, K SHIRAKATA, M PATERSON, BM AF MITSUI, K SHIRAKATA, M PATERSON, BM TI PHOSPHORYLATION INHIBITS THE DNA-BINDING ACTIVITY OF MYOD HOMODIMERS BUT NOT MYOD-E12 HETERODIMERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; MYOGENIC DETERMINATION FACTORS; MUSCLE-SPECIFIC TRANSCRIPTION; GENE FAMILY; ENHANCER; ACTIVATION; REGION; MEMBER; DIFFERENTIATION; DIMERIZATION AB MyoD is a member of the basic helix-loop-helix (bHLH) family of muscle gene regulatory proteins that includes myogenin, myf-5, and MRF4. These proteins have been shown to heterodimerize with E2A bHLH proteins, E12/E47, and to bind to a consensus sequence known as an E-box, CANNTG, the target for transcriptional activation by these myogenic regulators. MyoD is also a phosphorylated nuclear protein that is present in muscle cells prior to the transcriptional activation of the muscle-specific genes, many of which contain E-box elements in their regulatory regions. Here we report that phosphorylated chicken MyoD, called CMD1, produced in sf9 cells using the baculovirus system, is qualitatively similar to CMD1 isolated by immunoaffinity purification from primary cultures of embryonic chick breast muscle. Functional analysis of phosphorylated and dephosphorylated CMD1 produced in sf9 cells indicates that, in the presence of magnesium, DNA binding of phosphorylated CMD1 is inhibited whereas binding in association with E12 is not affected. However, CMD1 binding alone is equally efficient when either EDTA is added in excess or dephosphorylated or bacterially expressed CMD1 is used in the assay. Our results suggest that cellular phosphorylation changes the CMD1 homodimer-heterodimer equilibrium which, in turn, modulates and/or eliminates binding site competition between CMD1 homodimers and CMD1/E-protein heterodimers in the cell. C1 NCI,BIOCHEM LAB,BLDG 37,RM 4A-21,BETHESDA,MD 20892. NR 35 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1993 VL 268 IS 32 BP 24415 EP 24420 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF294 UT WOS:A1993MF29400103 PM 8226992 ER PT J AU XING, X MCDIARMID, R PHILIS, JG GOODMAN, L AF XING, X MCDIARMID, R PHILIS, JG GOODMAN, L TI VIBRATIONAL ASSIGNMENTS IN THE 3P RYDBERG STATES OF ACETONE SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SPECTRA AB The 2 and 3 photon resonantly enhanced multiphoton ionization spectra of the 3p Rydberg <-- X transitions of acetone and acetone-d6 were remeasured and reanalyzed. Seven of the eight a1 and one b1 vibrational modes were assigned. On the basis of these assigned fundamental frequencies the anomalous isotope shift of the origin of the A1 transition was rationalized, the contribution of the nonbonding electrons to the scissors force constant was demonstrated, and a location for the A1 pipi* valence excited transition was proposed. C1 UNIV IOANNINA,DEPT PHYS,IOANNINA,GREECE. RUTGERS UNIV,WRIGHT & RIEMAN CHEM LABS,NEW BRUNSWICK,NJ 08903. RP XING, X (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 23 TC 35 Z9 35 U1 0 U2 4 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 15 PY 1993 VL 99 IS 10 BP 7565 EP 7573 DI 10.1063/1.465686 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA MH744 UT WOS:A1993MH74400029 ER PT J AU YORK, DM DARDEN, TA PEDERSEN, LG AF YORK, DM DARDEN, TA PEDERSEN, LG TI THE EFFECT OF LONG-RANGE ELECTROSTATIC INTERACTIONS IN SIMULATIONS OF MACROMOLECULAR CRYSTALS - A COMPARISON OF THE EWALD AND TRUNCATED LIST METHODS SO JOURNAL OF CHEMICAL PHYSICS LA English DT Note ID MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; FORCE-FIELD; PROTEINS; WATER AB Simulations of the HIV-1 protease unit cell using a 9 angstrom. cutoff, 9/18 angstrom ''twin-range'' cutoff, and full Ewald sums have been carried out to 300 ps. The results indicate that long-range electrostatic interactions are essential for proper representation of the HIV-1 protease crystal structure. The 9 angstrom simulation did not converge in 300 ps. Inclusion of a 9/18 angstrom ''twin-range'' cutoff showed significant improvement. Simulation using the Ewald summation convention gave the best overall agreement with x-ray crystallographic data, and showed the least internal differences in the time average structures of the asymmetric units. The Ewald simulation represents an efficient implementation of the Particle Mesh Ewald method [Darden et al., J. Chem. Phys. 98, 10 089 (1993)], and illustrates the importance of including long-range electrostatic forces in large macromolecular systems. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP YORK, DM (reprint author), UNIV N CAROLINA,CHAPEL HILL,NC 27599, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 18 TC 338 Z9 342 U1 4 U2 51 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 15 PY 1993 VL 99 IS 10 BP 8345 EP 8348 DI 10.1063/1.465608 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA MH744 UT WOS:A1993MH74400110 ER PT J AU SHANTI, KN MARTIN, BM NAGPAL, S METCALFE, DD RAO, PVS AF SHANTI, KN MARTIN, BM NAGPAL, S METCALFE, DD RAO, PVS TI IDENTIFICATION OF TROPOMYOSIN AS THE MAJOR SHRIMP ALLERGEN AND CHARACTERIZATION OF ITS IGE-BINDING EPITOPES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; POLLEN ALLERGEN; DETERMINANTS; PROTEINS; INDIVIDUALS; FRAGMENTS; CLEAVAGE; PEPTIDES; COD AB The major heat-stable shrimp allergen (designated as Sa-II), capable of provoking IgE-mediated immediate type hypersensitivity reactions after the ingestion of cooked shrimp, has been shown to be a 34-kDa heat-stable protein containing 300 amino acid residues. Here, we report that a comparison of amino acid sequences of different peptides generated by proteolysis of Sa-II revealed an 86% homology with tropomyosin from Drosophila melanogaster, suggesting that Sa-II could be the shrimp muscle protein tropomyosin. To establish that Sa-II is indeed tropomyosin, the latter was isolated from uncooked shrimp (Penaeus indicus) and its physico-chemical and immunochemical properties were compared with those of Sa-II. Both tropomyosin and Sa-II had the same molecular mass and focused in the isoelectric pH range of 4.8 to 5.4. In the presence of 6 M urea, the mobility of both Sa-II and shrimp tropomyosin shifted to give an apparent molecular mass of 50 kDa, which is a characteristic property of tropomyosins. Shrimp tropomyosin bound to specific IgE antibodies in the sera of shrimp-sensitive patients as assessed by competitive ELISA inhibition and Western blot analysis. Tryptic maps of both Sa-II and tropomyosin as obtained by reverse phase HPLC were superimposable. Dot-blot and competitive ELISA inhibition using sera of shrimp-sensitive patients revealed that antigenic as well as allergenic activities were associated with two peptide fractions. These IgE-binding tryptic peptides were purified and sequenced. Mouse anti-anti-idiotypic antibodies raised against Sa-II specific human idiotypic antibodies recognized not only tropomyosin but also the two allergenic peptides, thus suggesting that these peptides represent the major IgE binding epitopes of tropomyosin. A comparison of the amino acid sequence of shrimp tropomyosin in the region of IgE binding epitopes (residues 50-66 and 153-161) with the corresponding regions of tropomyosins from different vertebrates confirmed lack of allergenic cross-reactivity between tropomyosins from phylogenetically distinct species. C1 INDIAN INST SCI,DEPT BIOCHEM,IMMUNOL & ALLERG DIS LAB,BANGALORE 560012,KARNATAKA,INDIA. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. RI Nagpal, Sunil/A-8007-2009 NR 33 TC 232 Z9 256 U1 3 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1993 VL 151 IS 10 BP 5354 EP 5363 PG 10 WC Immunology SC Immunology GA MF995 UT WOS:A1993MF99500025 PM 7693809 ER PT J AU CHOI, OH LEE, JH KASSESSINOFF, T CUNHAMELO, JR JONES, SVP BEAVEN, MA AF CHOI, OH LEE, JH KASSESSINOFF, T CUNHAMELO, JR JONES, SVP BEAVEN, MA TI ANTIGEN AND CARBACHOL MOBILIZE CALCIUM BY SIMILAR MECHANISMS IN A TRANSFECTED MAST-CELL LINE (RBL-2H3 CELLS) THAT EXPRESSES ML MUSCARINIC RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; CROMOLYN-BINDING-PROTEIN; LACRIMAL ACINAR-CELLS; FC-EPSILON RECEPTOR; INOSITOL 1,4,5-TRISPHOSPHATE; TYROSINE PHOSPHORYLATION; HISTAMINE-SECRETION; IMMUNOGLOBULIN-E; PLASMA-MEMBRANE; CROSS-LINKING AB Because of unresolved questions about the mechanism of Ag-stimulated Ca2+ influx, Ca2+ mobilization in response to carbachol and Ag was compared in transfected rat basophilic RBL-2H3(ml) cells that expressed both Fcepsilon and ml muscarinic receptors. Although the stimulants activated phospholipase C via different coupling mechanisms, a G protein for carbachol or a tyrosine kinase for Ag, they released Ca2+ from the same intracellular pool and used the same or very similar mechanisms for influx of Ca2+ as indicated by the similar patterns of inhibition of uptake of Ca-45(2+) by various cations. With both stimulants, influx and sustained increases in free cytosolic Ca2+ ([Ca2+]i) were associated with relatively small increases in inositol 1,4,5-trisphosphate (IP3). Blockade of Ca2+ influx resulted in rapid decline in [Ca2+]i to basal levels; resumption of influx caused a substantial ''spike'' in [Ca2+]i before [Ca2+]i reequilibrated at the same former steady-state levels but without perturbing levels of IP3. Thus, the refilling and discharge of Ca2+ from IP3-sensitive stores might occur synchronously on resumption of influx, or asynchronously during sustained influx and elevation of [Ca2+]i. Together, the results suggested that influx of Ca2+ in response to stimulation via Fcepsilon receptors occurred through a pathway, analogous to that observed with other types of stimulants, in which Ca2+ influx follows emptying of intracellular Ca2+ stores by IP3. Also, secretion was highly dependent on this IP3-dependent pathway. C1 NINCDS,BIOPHYS LAB,BETHESDA,MD 20892. UFMG,FM,DEPT SURG,BELO HORIZON,MG,BRAZIL. RP CHOI, OH (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N108,BETHESDA,MD 20892, USA. RI Cunha-Melo, Jose Renan/C-6262-2013 NR 40 TC 59 Z9 59 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 NOV 15 PY 1993 VL 151 IS 10 BP 5586 EP 5595 PG 10 WC Immunology SC Immunology GA MF995 UT WOS:A1993MF99500048 PM 8228248 ER PT J AU DONNELLY, RP CROFFORD, LJ FREEMAN, SL BURAS, J REMMERS, E WILDER, RL FENTON, MJ AF DONNELLY, RP CROFFORD, LJ FREEMAN, SL BURAS, J REMMERS, E WILDER, RL FENTON, MJ TI TISSUE-SPECIFIC REGULATION OF IL-6 PRODUCTION BY IL-4 - DIFFERENTIAL-EFFECTS OF IL-4 ON NUCLEAR FACTOR-KAPPA-B ACTIVITY IN MONOCYTES AND FIBROBLASTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN RECOMBINANT INTERLEUKIN-4; HEPATOCYTE-STIMULATING FACTOR; GENE-EXPRESSION; ENDOTHELIAL-CELLS; RHEUMATOID-ARTHRITIS; TRANSCRIPTION FACTOR; BLOOD MONOCYTES; FACTOR-ALPHA; HUMAN PROINTERLEUKIN-1-BETA AB IL-4 inhibits production of certain proinflammatory cytokines, including IL-1beta, TNF-alpha, and IL-6, by activated monocytes. Although monocytes are a major source of IL-6, other cell types such as fibroblasts and endothelial cells can also express this cytokine. To determine whether IL-4 inhibits IL-6 expression in non-hemopoietic cells, we investigated the effects of IL-4 on IL-6 production in both primary human fibroblasts and fibroblast lines. Rheumatoid synovial fibroblasts were evaluated in these studies because, like monocytes, they produce high levels of IL-6 when stimulated with IL-1. Although peripheral blood monocytes did not constitutively express IL-6 mRNA or protein, stimulation with IL-1 or LPS induced de novo IL-6 expression in these cells. In contrast, synovial fibroblasts displayed a significant basal level of IL-6 production, which was markedly increased after stimulation with IL-1. IL-4 suppressed IL-6 expression in monocytes, but did not inhibit IL-6 production in synovial fibroblasts. The inability of IL-4 to suppress IL-6 synthesis in rheumatoid synovial fibroblasts was not caused by a lack of IL-4R and was not unique to these cells because IL-4 also failed to inhibit IL-6 production in normal fibroblast lines derived from other tissues. Inhibition of IL-6 production by IL-4 in monocytes was associated with decreased nuclear NF-kappaB levels. However, IL-4 does not globally suppress the activity of all DNA-binding proteins because IL-4 treatment did not reduce the levels of NF-IL-6 or NF-IL-1betaB in the same cells. Because NF-kappaB activation is required for transcription of many cytokine genes, including IL-6, the ability of IL-4 to suppress NF-kappaB activity in monocytes suggests a potential mechanism by which this molecule may inhibit the expression of multiple cytokines. C1 NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892. BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,BOSTON,MA 02118. RP DONNELLY, RP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BLDG 29A,ROOM 2B-11,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 FU NIAID NIH HHS [AI 29088] NR 65 TC 83 Z9 83 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1993 VL 151 IS 10 BP 5603 EP 5612 PG 10 WC Immunology SC Immunology GA MF995 UT WOS:A1993MF99500050 PM 8228249 ER PT J AU GANDJBAKHCHE, AH TAITELBAUM, H WEISS, GH AF GANDJBAKHCHE, AH TAITELBAUM, H WEISS, GH TI RANDOM-WALK ANALYSIS OF TIME-RESOLVED TRANSILLUMINATION MEASUREMENTS IN OPTICAL IMAGING SO PHYSICA A LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL BAR-ILAN CONFERENCE ON FRONTIERS IN CONDENSED MATTER PHYSICS CY MAR 15-18, 1993 CL BAR-ILAN UNIV, DEPT PHYS, RAMAT GAN, ISRAEL SP JACK & PEARL RESNICK INST ADV TECHNOL HO BAR-ILAN UNIV, DEPT PHYS ID MEDIA; DIFFUSION; TISSUE AB Data relating photon migration in human tissue can be obtained from experiments in which laser light is injected into one face of a finite slab of tissue and detected at the opposite face. From the results of such experiments one would like to infer optical properties of the underlying tissue which are related to its biological properties. Random walk theory has been successfully applied to the translation of such data into the physical parameters that characterize properties of the tissue. We here outline a technique based on the theory of random walks for analyzing how well time-resolved transillumination experiments may be expected to perform for detecting hidden inclusions which have a greater absorption than surrounding tissue. We use an asymptotic evaluation of exact results to determine the degree to which detection is possible. C1 BAR ILAN UNIV,JEROME SCHOTTENSTEIN CELLSCAN CTR,IL-52100 RAMAT GAN,ISRAEL. RP GANDJBAKHCHE, AH (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD NOV 15 PY 1993 VL 200 IS 1-4 BP 212 EP 221 DI 10.1016/0378-4371(93)90519-A PG 10 WC Physics, Multidisciplinary SC Physics GA MJ558 UT WOS:A1993MJ55800022 ER PT J AU GITTERMAN, M KIEFER, J AF GITTERMAN, M KIEFER, J TI 2-STATE SYSTEM IN AN OSCILLATING FIELD SO PHYSICA A LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL BAR-ILAN CONFERENCE ON FRONTIERS IN CONDENSED MATTER PHYSICS CY MAR 15-18, 1993 CL BAR-ILAN UNIV, DEPT PHYS, RAMAT GAN, ISRAEL SP JACK & PEARL RESNICK INST ADV TECHNOL HO BAR-ILAN UNIV, DEPT PHYS ID STOCHASTIC RESONANCE AB We consider two states connected by two channels, one of which is activated but the other has no potential barrier. The height of the barrier is oscillating together with an external ac-field. We find that an external field shifts the average populations of the states and tends to equalize them. The steady-state flux circulates along the close circuit formed by these channels. C1 BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,BETHESDA,MD 20892, USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD NOV 15 PY 1993 VL 200 IS 1-4 BP 258 EP 266 DI 10.1016/0378-4371(93)90524-8 PG 9 WC Physics, Multidisciplinary SC Physics GA MJ558 UT WOS:A1993MJ55800027 ER PT J AU TAITELBAUM, H AF TAITELBAUM, H TI SEGREGATION IN REACTION-DIFFUSION SYSTEMS SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID NEAREST-NEIGHBOR DISTANCES; INITIALLY SEPARATED REACTANTS; REACTION FRONT; STATISTICAL PROPERTIES; REACTION-KINETICS; SINGLE TRAP; LIMITED REACTION; IMPERFECT TRAP; 2 DIMENSIONS; MOBILE TRAP AB Segregation of reactants in reaction-diffusion systems is a spatial structure that can be formed either as a result of a dynamical process or as an initially prepared system. In this paper we review our recent results on both such systems. First we study the dynamic segregation at a single trap, in particular in the presence of fields and disorder. Then we study properties of the dynamic reaction front produced due to initial segregation of the reactants in the A + B --> C system. Both systems are shown to exhibit anomalous kinetic properties. RP NIMH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NR 45 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD NOV 15 PY 1993 VL 200 IS 1-4 BP 155 EP 164 DI 10.1016/0378-4371(93)90513-4 PG 10 WC Physics, Multidisciplinary SC Physics GA MJ558 UT WOS:A1993MJ55800016 ER PT J AU CALLAN, MFC REYBURN, HT BOWNESS, P OTTENHOFF, TH ENGEL, I KLAUSNER, RD BELL, JI MCMICHAEL, A AF CALLAN, MFC REYBURN, HT BOWNESS, P OTTENHOFF, TH ENGEL, I KLAUSNER, RD BELL, JI MCMICHAEL, A TI A METHOD FOR PRODUCING MONOCLONAL-ANTIBODIES TO HUMAN T-CELL-RECEPTOR BETA-CHAIN VARIABLE REGIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTIGEN RECEPTOR; LYMPHOCYTES-T; EXPRESSION; REPERTOIRE; GENERATION; USAGE AB Study of the T-cell repertoire in humans has been hampered by the lack of monoclonal antibodies (mAbs) to the T-cell receptor (TCR) variable region (V) gene products. We describe a method for producing mAbs to the human TCR beta-chain V (V(beta)) gene products in which mice were immunized with a rat basophil cell line (RBL-2H3) transfected with the extracellular domain of the TCR heterodimer fused to the zeta chain of CD3. These cells acted as excellent immunogens for raising anti-TCR mAb and also formed the basis of a rapid screening assay. We generated mAbs against V(beta) protein of the TCR, showed that these mAbs stained almost-equal-to 1% of peripheral blood T cells, and further showed that the mAbs could stimulate proliferation of these T cells. We then characterized the mAbs by amplifying TCR cDNA derived from mAb-stimulated cells and sequencing the beta chain. All clones sequenced used the V(beta)7.1. chain, proving conclusively that the mAbs generated were specific for V(beta)7.1 subfamily. This method generates mAbs to human TCR V(beta) proteins efficiently and might allow production of a complete panel of mAbs directed against human TCR V(beta) proteins. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP CALLAN, MFC (reprint author), JOHN RADCLIFFE HOSP,INST MOLEC MED,MOLEC IMMUNOL GRP,OXFORD OX3 9DU,ENGLAND. RI Reyburn, Hugh/B-4338-2009 FU Wellcome Trust NR 29 TC 18 Z9 18 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 NOV 15 PY 1993 VL 90 IS 22 BP 10454 EP 10458 DI 10.1073/pnas.90.22.10454 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200010 PM 8248131 ER PT J AU MERCHENTHALER, I LENNARD, DE LOPEZ, FJ NEGROVILAR, A AF MERCHENTHALER, I LENNARD, DE LOPEZ, FJ NEGROVILAR, A TI NEONATAL IMPRINTING PREDETERMINES THE SEXUALLY DIMORPHIC, ESTROGEN-DEPENDENT EXPRESSION OF GALANIN IN LUTEINIZING-HORMONE-RELEASING HORMONE NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COLOCALIZATION; DOUBLE LABELING IMMUNOCYTOCHEMISTRY; HYPOTHALAMIC SEXUAL DIFFERENTIATION; REPRODUCTION ID MEDIAL PREOPTIC AREA; BRAIN; DIFFERENTIATION; RAT; BEHAVIOR AB The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility-i.e., gender-specific determination of LHRH neurons coexpressing GAL-was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of LHRH neurons that could synchronize their activity to control the estrous cycle in rats. C1 NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, REPROD NEUROENDOCRINOL SECT, RES TRIANGLE PK, NC 27709 USA. RP MERCHENTHALER, I (reprint author), NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, FUNCT MORPHOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 33 TC 41 Z9 41 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 NOV 15 PY 1993 VL 90 IS 22 BP 10479 EP 10483 DI 10.1073/pnas.90.22.10479 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200015 PM 7504265 ER PT J AU NAKAYAMA, T WIEST, DL ABRAHAM, KM MUNITZ, TI PERLMUTTER, RM SINGER, A AF NAKAYAMA, T WIEST, DL ABRAHAM, KM MUNITZ, TI PERLMUTTER, RM SINGER, A TI DECREASED SIGNALING COMPETENCE AS A RESULT OF RECEPTOR OVEREXPRESSION - OVEREXPRESSION OF CD4 REDUCES ITS ABILITY TO ACTIVATE P56(LCK) TYROSINE KINASE AND TO REGULATE T-CELL ANTIGEN RECEPTOR EXPRESSION IN IMMATURE CD4+CD8+ THYMOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODY; CYTOPLASMIC DOMAINS; PROTEIN-KINASE; P56LCK; MICE; DIFFERENTIATION; MOLECULES; SELECTION; SEQUENCES; REGION AB Thymic selection of the developing T-cell repertoire occurs in immature CD4+CD8+ thymocytes, with the fate of individual thymocytes determined by the specificity of T-cell antigen receptor they express. However, T-cell antigen receptor expression in immature CD4+CD8+ thymocytes is actively down-regulated in CD4+CD8+ thymocytes by CD4-mediated tyrosine kinase signals that are generated in the thymus as a result of CD4 engagement by intrathymic ligands. In the present study we have examined the effect of CD4 overexpression in CD4+CD8+ thymocytes on activation of CD4-associated p56lck tyrosine kinase and regulation of T-cell antigen receptor expression. Augmented CD4 expression in CD4+CD8+ thymocytes did not result in commensurate increases in associated p56lck molecules, so that CD4 expression was quantitatively disproportionate to that of its associated signaling molecule p56lck. Interestingly, we found that CD4 overexpression significantly interfered with the ability of CD4 crosslinking to activate associated p56lck molecules and significantly interfered with the ability of CD4 to regulate T-cell antigen receptor expression. Thus, this study provides an example in which receptor overexpression leads to decreased receptor signaling competence. C1 NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA 98195. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. RI Nakayama, Toshinori/E-1067-2017; OI Wiest, David/0000-0002-0792-3188 NR 23 TC 25 Z9 25 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 NOV 15 PY 1993 VL 90 IS 22 BP 10534 EP 10538 DI 10.1073/pnas.90.22.10534 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200026 PM 7902564 ER PT J AU JIANG, BM MONROE, SS KOONIN, EV STINE, SE GLASS, RI AF JIANG, BM MONROE, SS KOONIN, EV STINE, SE GLASS, RI TI RNA SEQUENCE OF ASTROVIRUS - DISTINCTIVE GENOMIC ORGANIZATION AND A PUTATIVE RETROVIRUS-LIKE RIBOSOMAL FRAMESHIFTING SIGNAL THAT DIRECTS THE VIRAL REPLICASE SYNTHESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATITIS-E VIRUS; CYSTEINE PROTEASES; MOLECULAR-CLONING; PROTEINS; DOMAIN; GASTROENTERITIS; SUPERFAMILY; POLYPROTEIN; DELINEATION; PSEUDOKNOT AB The genomic RNA of human astrovirus was sequenced and found to contain 6797 nt organized into three open reading frames (1a, 1b, and 2). A potential ribosomal frameshift site identified in the overlap region of open reading frames 1a and 1b consists of a ''shifty'' heptanucleotide and an RNA stem-loop structure that closely resemble those at the gag-pro junction of some retroviruses. This translation frameshift may result in the suppression of in-frame amber termination at the end of open reading frame 1a and the synthesis of a nonstructural, fusion polyprotein that contains the putative protease and RNA-dependent RNA polymerase. Comparative sequence analysis indicated that the protease and polymerase of astrovirus are only distantly related to the respective enzymes of other positive-strand RNA viruses. The astrovirus polyprotein lacks the RNA helicase domain typical of other positive-strand RNA viruses of similar genome size. The genomic organization and expression strategy of astrovirus, with the protease and the polymerase brought together by predicted frameshift, most closely resembled those of plant luteoviruses. Specific features of the sequence and genomic organization support the classification of astroviruses as an additional family of positive-strand RNA viruses, designated Astroviridae. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. RP JIANG, BM (reprint author), CTR DIS CONTROL & PREVENT,VIRAL GASTROENTERITIS SECT,ATLANTA,GA 30333, USA. OI Monroe, Stephan/0000-0002-5424-716X NR 51 TC 162 Z9 165 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1993 VL 90 IS 22 BP 10539 EP 10543 DI 10.1073/pnas.90.22.10539 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200027 PM 8248142 ER PT J AU ARISPE, N POLLARD, HB ROJAS, E AF ARISPE, N POLLARD, HB ROJAS, E TI GIANT MULTILEVEL CATION CHANNELS FORMED BY ALZHEIMER-DISEASE AMYLOID BETA-PROTEIN [A-BETA-P-(1-40)] IN BILAYER-MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LIPOSOMES ID PEPTIDE; NEUROTOXICITY; AGGREGATION; PRECURSOR; CELLS; CDNA AB We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein [AbetaP-(1-40)] can form cation-selective channels when incorporated into planar lipid bilayers by fusion of liposomes containing the peptide. Since AbetaP-(1-40) comprises portions of the putative extracellular and membrane-spanning domains of the amyloid precursor protein (APP751), we suggested that the channel-forming property could be the underlying cause of amyloid neurotoxicity. The peptide has been proposed to occur in vivo in both membrane-bound and soluble forms, and we now report that soluble AbetaP-(1-40) can also form similar channels in solvent-free lipid bilayers formed at the tip of a patch pipet, as well as in the planar lipid bilayer system. As in the case of liposome-mediated incorporation, the amyloid channel activity in the patch pipet exhibits multiple conductance levels between 40 and 400 pS, cation selectivity, and sensitivity to tromethamine (Tris). Further studies with AbetaP channels incorporated into planar lipid bilayers from the liposome complex have also revealed that the channel activity can express spontaneous transitions to a much higher range of conductances between 400 and 4000 pS. Under these conditions, the amyloid channel continues to be cation selective. Amyloid channels were insensitive to nitrendipine at either conductance range. We calculate that if such channels were expressed in cells, the ensuing ion fluxes down their electrochemical potential gradients would be homeostatically dissipative. We therefore interpret these data as providing further support for the concept that cell death in Alzheimer disease may be due to amyloid ion-channel activity. RP ARISPE, N (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 24 TC 406 Z9 415 U1 2 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1993 VL 90 IS 22 BP 10573 EP 10577 DI 10.1073/pnas.90.22.10573 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200034 PM 7504270 ER PT J AU FLOTTE, TR AFIONE, SA CONRAD, C MCGRATH, SA SOLOW, R OKA, H ZEITLIN, PL GUGGINO, WB CARTER, BJ AF FLOTTE, TR AFIONE, SA CONRAD, C MCGRATH, SA SOLOW, R OKA, H ZEITLIN, PL GUGGINO, WB CARTER, BJ TI STABLE IN-VIVO EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR WITH AN ADENOASSOCIATED VIRUS VECTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; ADENOASSOCIATED VIRUS; GENE-EXPRESSION; INTEGRATION; DNA; AMPLIFICATION; EPITHELIUM; SITE AB Adeno-associated virus (AAV) vectors expressing the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA complement the cystic fibrosis (CF) defect in vitro. Unlike other DNA virus vectors, AAV is a stably integrating virus, which could make possible long-term in vivo complementation of the CF defect in the airway epithelium. We report AAV-CFTR gene transfer and expression after infection of primary CF nasal polyp cells and after in vivo delivery of AAV-CFTR vector to one lobe of the rabbit lung through a fiberoptic bronchoscope. In the rabbit, vector DNA could be detected in the infected lobe up to 6 months after administration. A 26-amino acid polypeptide sequence unique to the recombinant AAV-CFTR protein was used to generate both oligonucleotide probes and a polyclonal antibody which allowed the unambiguous identification of vector RNA and CFTR protein expression. With these reagents, CFTR RNA and protein were detected in the airway epithelium of the infected lobe for up to 6 months after vector administration. AAV vectors do, therefore, efficiently promote in vivo gene transfer to the airway epithelium which is stable over several months. These findings indicate that AAV-CFTR vectors could potentially be very useful for gene therapy. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. TARGETED GENET CORP,SEATTLE,WA 98101. RP FLOTTE, TR (reprint author), JOHNS HOPKINS UNIV,SCH MED,EUDOWOOD DIV PEDIAT RESP SCI,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 23 TC 384 Z9 390 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1993 VL 90 IS 22 BP 10613 EP 10617 DI 10.1073/pnas.90.22.10613 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200042 PM 7504271 ER PT J AU YONEDA, K STEINERT, PM AF YONEDA, K STEINERT, PM TI OVEREXPRESSION OF HUMAN LORICRIN IN TRANSGENIC MICE PRODUCES A NORMAL PHENOTYPE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CROSS-LINKED ENVELOPE; CELL-ENVELOPE; EPIDERMAL TRANSGLUTAMINASE; CORNIFIED ENVELOPE; GLYCINE LOOPS; PROTEINS; KERATINOCYTES; PRECURSOR; SUBSTRATE; CALCIUM AB The cornified cell envelope (CE) of terminally differentiating stratified squamous epithelial cells is a complex multiprotein assembly about 15 nm thick of which loricrin is a major component. We have produced transgenic mice bearing the human loricrin transgene in order to study the role of loricrin in CE assembly, structure, and function. By analyses of RNA and protein, we show that the human transgene is expressed in mouse epithelial tissues in an appropriate developmental manner but at an overall level about twice that of endogenous mouse loricrin. Thus the 20-kbp construct used contains all necessary regulatory elements. By immunogold electron microscopy, all of the expressed protein is incorporated into the CE. That no alternations were noted indicates that overproduction of the loricrin component of the CE does not affect the flexible structure or function of the epithelial tissues. Furthermore, these data imply that loricrin may be the last protein to be deposited onto, and thus lines, the intracellular surface of the CE, where it may be accessible to interact with the subjacent keratin intermediate-filament network. RP YONEDA, K (reprint author), NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892, USA. NR 26 TC 59 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 NOV 15 PY 1993 VL 90 IS 22 BP 10754 EP 10758 DI 10.1073/pnas.90.22.10754 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200071 PM 8248167 ER PT J AU YEOMAN, H GRESS, RE BARE, CV LEARY, AG BOYSE, EA BARD, J SHULTZ, LD HARRIS, DT DELUCA, D AF YEOMAN, H GRESS, RE BARE, CV LEARY, AG BOYSE, EA BARD, J SHULTZ, LD HARRIS, DT DELUCA, D TI HUMAN BONE-MARROW AND UMBILICAL-CORD BLOOD-CELLS GENERATE CD4+ AND CD8+ SINGLE-POSITIVE T-CELLS IN MURINE FETAL THYMUS ORGAN-CULTURE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYMOCYTES; INVITRO; DIFFERENTIATION; EXPRESSION; INVIVO AB Murine fetal thymus lobes isolated from both normal and scid/scid mice can be colonized by donor cells from either human bone marrow or human umbilical cord blood in vitro. Subsequent organ culture results in a transient production of a few CD4+ CD8+ (double-positive) cells and then the accumulation of CD4+ or CD8+ (single-positive) T cells. A significant number of immature T-cell intermediates (e.g., CD8low, CD3-/low cells) were present in early organ cultures, suggesting that these were progenitors of the mature CD3+/high single-positive T cells that dominated late cultures. Depletion of mature T cells from the donor-cell populations did not affect their ability to colonize thymus lobes. However, colonization depended on the presence of CD7+ progenitor T cells. Limiting dilution experiments using mature T-cell populations (human peripheral blood leukocytes, human bone marrow cells, and human umbilical cord blood cells) suggested that thymic organ culture supports the growth of progenitor T cells but does not support the growth of mature human T cells. Each of these donor populations produced single-positive populations with different CD4/CD8 ratios, suggesting that precursor cells from different sources differ qualitatively in their capacity to differentiate into T cells. C1 UNIV ARIZONA,DEPT MICROBIOL & IMMUNOL,TUCSON,AZ 85721. NCI,BETHESDA,MD 20892. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29403. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29403. JACKSON LAB,BAR HARBOR,ME 04609. FU NCI NIH HHS [CA 39827]; NIAID NIH HHS [AI 30389, AI/GM 29407] NR 22 TC 50 Z9 51 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 NOV 15 PY 1993 VL 90 IS 22 BP 10778 EP 10782 DI 10.1073/pnas.90.22.10778 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200076 PM 7902570 ER PT J AU ROTH, DB ZHU, CM GELLERT, M AF ROTH, DB ZHU, CM GELLERT, M TI CHARACTERIZATION OF BROKEN DNA-MOLECULES ASSOCIATED WITH V(D)J RECOMBINATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DOUBLE-STRAND BREAKS; CODING ENDS; SIGNAL ENDS; RECOMBINATION SIGNAL SEQUENCES; DNA HAIRPINS ID SITE-SPECIFIC RECOMBINATION; NONHOMOLOGOUS RECOMBINATION; MOUSE THYMOCYTES; CODING SEGMENTS; MAMMALIAN-CELLS; STRAND TRANSFER; CLEAVAGE; MECHANISM; REARRANGEMENT; SEQUENCES AB We previously demonstrated that DNA molecules with double-strand breaks at variable-(diversity)-joining [V(D)J] recombination signal sequences are relatively abundant in mouse thymocytes. This abundance strongly suggests that the mechanism of V(D)J recombination involves double-strand cleavage at recombination signals. As a first step toward understanding the mechanism of cleavage, we used a sensitive PCR assay to characterize the structure of one class of cleavage products, the signal ends, in detail. Here we demonstrate that most of these ends are blunt and terminate in 5' phosphoryl groups. Virtually all of the flush signal ends are full length. A minor subpopulation of broken ends terminates in short single-strand extensions. We have found no evidence for covalent DNA-protein linkages involving the signal ends. These data allow further refinement of the double-strand cleavage model for V(D)J recombination. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. RP ROTH, DB (reprint author), BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030, USA. NR 19 TC 149 Z9 150 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1993 VL 90 IS 22 BP 10788 EP 10792 DI 10.1073/pnas.90.22.10788 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200078 PM 8248171 ER PT J AU NOBLE, JA INNIS, MA KOONIN, EV RUDD, KE BANUETT, F HERSKOWITZ, I AF NOBLE, JA INNIS, MA KOONIN, EV RUDD, KE BANUETT, F HERSKOWITZ, I TI THE ESCHERICHIA-COLI HFLA LOCUS ENCODES A PUTATIVE GTP-BINDING PROTEIN AND 2 MEMBRANE-PROTEINS, ONE OF WHICH CONTAINS A PROTEASE-LIKE DOMAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BACTERIOPHAGE-LAMBDA; PROTEOLYSIS; CII-PROTEIN; LYSIS LYSOGENY DECISION ID LYSIS-LYSOGENY DECISION; BACTERIOPHAGE-LAMBDA; PHAGE-LAMBDA; CII PROTEIN; CLP-P; SEQUENCE; GENE; RNA; IDENTIFICATION; CLONING AB The hflA (high frequency of lysogenization) locus of Escherichia coli governs the lysis-lysogeny decision of bacteriophage lambda by controlling stability of the phage cII protein. hflA contains three genes, hflX, hflK, and hflC, encoding polypeptides of 50, 46, and 37 kDa, respectively. We have determined the nucleotide sequence of 3843 base pairs containing hflA and have found three large open reading frames corresponding to hflX, hflK, and hflC. HflX contains the three sequence motifs typical of GTP-binding proteins and appears to be a member of a distinct family of putative GTPases. HflC and HflK appear to be integral membrane proteins which show some similarity to each other and to a human membrane protein. The C-terminal region of HflC contains a domain resembling the catalytic domain of ClpP, a bacterial ATP-dependent protease. We hypothesize that HflK and HflC constitute a distinct membrane-bound protease whose activity may be modulated by HflX GTPase. C1 UNIV CALIF SAN FRANCISCO, SCH MED, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. CETUS CORP, EMERYVILLE, CA 94608 USA. NR 41 TC 60 Z9 64 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 NOV 15 PY 1993 VL 90 IS 22 BP 10866 EP 10870 DI 10.1073/pnas.90.22.10866 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH322 UT WOS:A1993MH32200094 PM 8248183 ER PT J AU GUILLET, V LAPTHORN, A HARTLEY, RW MAUGUEN, Y AF GUILLET, V LAPTHORN, A HARTLEY, RW MAUGUEN, Y TI RECOGNITION BETWEEN A BACTERIAL RIBONUCLEASE, BARNASE, AND ITS NATURAL INHIBITOR, BARSTAR SO STRUCTURE LA English DT Article DE BARNASE; BARSTAR; PROTEIN-PROTEIN RECOGNITION; RNASE-INHIBITOR COMPLEX; X-RAY CRYSTALLOGRAPHY ID BACILLUS-AMYLOLIQUEFACIENS BARNASE; SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; ACTIVE-SITE; EXTRACELLULAR RIBONUCLEASE; PROTEIN-STRUCTURE; BINDING; ANGIOGENIN; COMPLEX; EXPRESSION AB Background: Protein-protein recognition is fundamental to most biological processes. The information we have so far on the interfaces between proteins comes largely from several protease-inhibitor and antigen-antibody complexes. Barnase, a bacterial ribonuclease, and barstar, its natural inhibitor, form a tight complex which provides a good model for the study and design of protein-protein non-covalent interactions. Results: Here we report the structure of a complex between barnase and a fully functional mutant of barstar determined by X-ray analysis. Barstar is composed of three parallel alpha-helices stacked against a three-stranded parallel beta-sheet, and sterically blocks the active site of the enzyme with an alpha-helix and adjacent loop. The buried surface in the interface between the two molecules totals 1630 Angstrom(2). The barnase-barstar complex is predominantly stabilized by charge interactions involving positive charges in the active site of the enzyme. Asp39 of barstar binds to the phosphate-binding site of barnase, mimicking enzyme-substrate interactions. Conclusion: The phosphate-binding site of the enzyme is the anchor point for inhibitor binding. We propose that this is also likely to be the case for other ribonuclease inhibitors. C1 CTR ETUD PHARMACEUT,PHYS LAB,CNRS,UPR 180,F-92296 CHATENAY MALABRY,FRANCE. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RI Guillet, Valerie/C-6058-2011 NR 55 TC 105 Z9 109 U1 2 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 15 PY 1993 VL 1 IS 3 BP 165 EP 176 DI 10.1016/0969-2126(93)90018-C PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NC279 UT WOS:A1993NC27900002 PM 16100951 ER PT J AU CONLAN, MG FOLSOM, AR FINCH, A DAVIS, CE SORLIE, P WU, KK AF CONLAN, MG FOLSOM, AR FINCH, A DAVIS, CE SORLIE, P WU, KK TI CORRELATION OF PLASMA PROTEIN-C LEVELS WITH CARDIOVASCULAR RISK-FACTORS IN MIDDLE-AGED ADULTS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID ISCHEMIC HEART-DISEASE; IMPROVED LIPOLYTIC EFFICIENCY; FACTOR-VII; ENZYMATIC DETERMINATION; HEMOSTATIC VARIABLES; THROMBOTIC DISEASE; DIABETES-MELLITUS; DEFICIENCY; COAGULATION; ANTIGEN AB To evaluate the association of plasma protein C levels with constitutional, socioeconomic, life-style and biochemical factors important in cardiovascular diseases, we measured protein C levels in 12,290 middle aged (45-64 years) subjects participating in the ARIC study. Protein C levels had a normal distribution with a mean value of 3.17 mug/ml. They were higher in women than men and in whites than blacks; higher in postmenopausal women and further increased by hormonal supplements. The age influence was inconsistent and was considered to be inconsequential. Protein C levels were positively correlated with body mass index, LDL-cholesterol, HDL-cholesterol, and triglycerides and negatively associated with cigarette smoking. These factors should be taken into consideration when establishing normal protein C levels and when analyzing the relation between protein C and arterial and venous thrombotic disorders. C1 UNIV TEXAS,SCH MED,DIV HEMATOL,6431 FANNIN,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,VASC BIOL RES CTR,HOUSTON,TX 77030. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,COLLABORAT STUDIES COORDINAT CTR,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-55021, N01-HC-55022] NR 39 TC 31 Z9 32 U1 0 U2 2 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 NOV 15 PY 1993 VL 70 IS 5 BP 762 EP 767 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA MJ283 UT WOS:A1993MJ28300009 PM 8128432 ER PT J AU MURPHY, DGM DECARLI, C DALY, E HAXBY, JV ALLEN, G WHITE, BJ MCINTOSH, AR POWELL, CM HORWITZ, B RAPOPORT, SI SCHAPIRO, MB AF MURPHY, DGM DECARLI, C DALY, E HAXBY, JV ALLEN, G WHITE, BJ MCINTOSH, AR POWELL, CM HORWITZ, B RAPOPORT, SI SCHAPIRO, MB TI X-CHROMOSOME EFFECTS ON FEMALE BRAIN - A MAGNETIC-RESONANCE-IMAGING STUDY OF TURNERS-SYNDROME SO LANCET LA English DT Article ID INACTIVATION; MEMORY AB Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD 12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p<0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres. C1 NIDDKD,CHEM BIOL LAB,CYTOGENET UNIT,BETHESDA,MD. NIH,MED GENET PROGRAM,BETHESDA,MD 20892. RP MURPHY, DGM (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009; McIntosh, Anthony/G-4955-2011; daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467; McIntosh, Anthony/0000-0002-1784-5662 NR 17 TC 146 Z9 146 U1 2 U2 8 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 13 PY 1993 VL 342 IS 8881 BP 1197 EP 1200 DI 10.1016/0140-6736(93)92184-U PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MG274 UT WOS:A1993MG27400008 PM 7901528 ER PT J AU SPORN, MB AF SPORN, MB TI CHEMOPREVENTION OF CANCER SO LANCET LA English DT Editorial Material ID RECEPTOR SUPERFAMILY; PREVENTION; CARCINOGENESIS; TAMOXIFEN; DISEASE; EFFICACY; TRIALS; TUMORS RP SPORN, MB (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 29 TC 66 Z9 66 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 13 PY 1993 VL 342 IS 8881 BP 1211 EP 1213 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA MG274 UT WOS:A1993MG27400013 PM 7901533 ER PT J AU DUBLIN, S BLATNER, WA WHITE, GC GOEDERT, JJ AF DUBLIN, S BLATNER, WA WHITE, GC GOEDERT, JJ TI PROCREATION AND HIV SO LANCET LA English DT Letter ID PARTNERS; WOMEN C1 UNIV N CAROLINA,DIV HEMATOL,CHAPEL HILL,NC 27514. RP DUBLIN, S (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 13 PY 1993 VL 342 IS 8881 BP 1241 EP 1242 DI 10.1016/0140-6736(93)92225-I PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MG274 UT WOS:A1993MG27400051 PM 7901561 ER PT J AU CORBELLINO, M LUSSO, P GALLO, RC PARRAVICINI, C GALLI, M MORONI, M AF CORBELLINO, M LUSSO, P GALLO, RC PARRAVICINI, C GALLI, M MORONI, M TI DISSEMINATED HUMAN HERPESVIRUS-6 INFECTION IN AIDS SO LANCET LA English DT Letter ID HHV-6; HBLV C1 OSPED L SACCO,MILAN,ITALY. UNIV MILAN,IST MALATTIE INFETT,I-20122 MILAN,ITALY. RP CORBELLINO, M (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 6 TC 78 Z9 79 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 13 PY 1993 VL 342 IS 8881 BP 1242 EP 1242 DI 10.1016/0140-6736(93)92226-J PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MG274 UT WOS:A1993MG27400052 PM 7901562 ER PT J AU ZOCCHI, A PERT, A AF ZOCCHI, A PERT, A TI INCREASES IN STRIATAL ACETYLCHOLINE BY SKF-38393 ARE MEDIATED THROUGH D(1) DOPAMINE-RECEPTORS IN STRIATUM AND NOT THE FRONTAL-CORTEX SO BRAIN RESEARCH LA English DT Article DE ACETYLCHOLINE; SKF-38393; STRIATUM; FRONTAL CORTEX; MICRODIALYSIS ID RAT NEOSTRIATUM INVITRO; CAUDATE-NUCLEUS; ENDOGENOUS ACETYLCHOLINE; TYROSINE-HYDROXYLASE; BRAIN MICRODIALYSIS; CHOLINERGIC NEURONS; GENE-EXPRESSION; D-2 RECEPTORS; CYCLIC-AMP; RELEASE AB It has been proposed by some that the D1 receptor effects are mediated through striatal actions while others have suggested that they are determined indirectly through the frontal cortex. The experiments reported here represent a further attempt to resolve this controversy. It was found that focal applications of the inactive and active enantiomers of SKF-38393 (a D1 dopamine receptor agonist) to the rat striatum via reverse dialysis increased extracellular acetylcholine (ACh) in a stereoselective manner. Infusions of SKF-38393 into the frontal cortex, on the other hand, were ineffective in altering striatal ACh. Furthermore, partial hemisections caudal to the frontal cortex did not alter the ability of systemically administrated SKF-38393 to increase striatal ACh. Taken together, these results suggest that at least some of the effects of D1 receptor agonists on striatal cholinergic function are mediated through actions in the striatum and not the frontal cortex. RP ZOCCHI, A (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 12 PY 1993 VL 627 IS 2 BP 186 EP 192 DI 10.1016/0006-8993(93)90319-I PG 7 WC Neurosciences SC Neurosciences & Neurology GA ME690 UT WOS:A1993ME69000002 PM 8298961 ER PT J AU MIHALY, A ENDRESZ, V ORAVECZ, T RAPP, UR KUHNT, U AF MIHALY, A ENDRESZ, V ORAVECZ, T RAPP, UR KUHNT, U TI IMMUNOHISTOCHEMICAL DETECTION OF RAF PROTEIN-KINASE IN CEREBRAL CORTICAL AREAS OF ADULT GUINEA-PIGS AND RATS SO BRAIN RESEARCH LA English DT Article DE PROTOONCOGENE; IMMUNOHISTOCHEMISTRY; NEOCORTEX; HIPPOCAMPUS; GUINEA PIG; RAT ID COMPLETE CODING SEQUENCE; SERINE THREONINE KINASE; SOMATIC SENSORY CORTEX; LONG-TERM POTENTIATION; II MUTANT MICE; VISUAL-CORTEX; GROWTH-FACTOR; DENTATE GYRUS; B-RAF; IMMUNOCYTOCHEMICAL LOCALIZATION AB The raf protooncogenes are the cellular counterparts of the v-raf oncogene expressed by a murine sarcoma virus. The raf protooncogenes encode cytoplasmic serine/threonine-specific protein kinases which can be activated from different growth factor receptors by phosphorylation. The mRNAs of raf protooncogenes are found in a large variety of normal adult tissues, including the central nervous system. As concerns the distribution and localization of their protein products (the raf kinases), very few data are to be found in the literature. This is the first detailed description of their light microscopic localization in neocortical and allocortical areas of rodents. Preembedding immunohistochemical studies were performed on vibratome sections from the brains of adult guinea pigs and albino rats. The localizations of two isoenzymes, raf-I kinase and B-raf kinase, were studied with the help of isoenzyme-specific polyclonal antibodies. Both of the antibodies detected raf protein-like immunoreactivity in many neurons and scattered glial cells of the sensory neocortex, and the cingular, pyriform, perirhinal and entorhinal allocortical areas. Pyramidal and non-pyramidal cells of Ammon's horn, granule cells of the dentate fascia and the large neurons in the hilar region were immunoreactive, too. The findings indicated that B-raf protein kinase and raf-1 kinase are present almost ubiquitously in the neurons of the investigated cortical structures. The intensity of staining obtained with serial dilutions of the antibodies indicated that the cytoplasmic concentration of B-raf kinase is tended to be higher than that of raf-1 kinase. The present findings suggested that the raf kinases are localized in postsynaptic structures, mainly in dendrites and cell bodies. Their cytosolic localization and their ability to undergo intracellular translocation during activation and phosphorylation raise the possibility that they play a pivotal role in the intracellular signalling of neurons. C1 ALBERT SZENT GYORGYI MED UNIV,DEPT MICROBIOL,SZEGED,HUNGARY. HUNGARIAN ACAD SCI,INST GENET,BIOL RES CTR,H-6701 SZEGED,HUNGARY. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. MAX PLANCK INST BIOPHYS CHEM,DEPT NEUROBIOL,W-3400 GOTTINGEN,GERMANY. RP MIHALY, A (reprint author), ALBERT SZENT GYORGYI MED UNIV,DEPT ANAT,POB 512,H-6701 SZEGED,HUNGARY. RI Mihaly, Andras/K-5096-2012 NR 60 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 12 PY 1993 VL 627 IS 2 BP 225 EP 238 DI 10.1016/0006-8993(93)90325-H PG 14 WC Neurosciences SC Neurosciences & Neurology GA ME690 UT WOS:A1993ME69000008 PM 8298966 ER PT J AU NACHEMSON, AK BENNETT, GJ AF NACHEMSON, AK BENNETT, GJ TI DOES PAIN DAMAGE SPINAL-CORD NEURONS - TRANSSYNAPTIC DEGENERATION IN RAT FOLLOWING A SURGICAL INCISION SO NEUROSCIENCE LETTERS LA English DT Article DE EXCITOTOXICITY; HYPERALGESIA; NMDA RECEPTOR; PAINFUL PERIPHERAL NEUROPATHY; TRANSSYNAPTIC DEGENERATION ID DORSAL HORN; PERIPHERAL MONONEUROPATHY; NEUROPATHY; STRYCHNINE AB In prior studies, rats with a chronic constriction injury to the sciatic nerve have been found to have small- to medium-sized, pyknotic, and hyperchromatic neurons ('dark neurons'; DNs) in spinal dorsal horn laminae I-III. It has been proposed that DNs are produced by an excitotoxic insult involving N-methyl-D-aspartate receptor activation subsequent to ectopic nociceptor discharge, and that at least some DNs are inhibitory interneurons whose functional impairment or death contributes to a central state of hyperexcitability that underlies neuropathic hyperalgesia and allodynia. We show here that laminae I-III DNs are also present 2 days after a surgical procedure that does not include major nerve damage. We propose that this is also the result of a nociceptor-driven excitotoxic insult and that the functional impairment of the affected neurons may contribute to postoperative pain and tenderness. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,BETHESDA,MD 20892. GOTHENBURG UNIV,SAHLGREN HOSP,DEPT ORTHOPAED,S-41124 GOTHENBURG,SWEDEN. NR 8 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 12 PY 1993 VL 162 IS 1-2 BP 78 EP 80 DI 10.1016/0304-3940(93)90564-2 PG 3 WC Neurosciences SC Neurosciences & Neurology GA MH359 UT WOS:A1993MH35900020 PM 8121641 ER PT J AU MOLCHAN, SE MANJI, H CHEN, G DOU, L LITTLE, J POTTER, WZ SUNDERLAND, T AF MOLCHAN, SE MANJI, H CHEN, G DOU, L LITTLE, J POTTER, WZ SUNDERLAND, T TI EFFECTS OF CHRONIC LITHIUM TREATMENT ON PLATELET PKC ISOZYMES IN ALZHEIMERS AND ELDERLY CONTROL SUBJECTS SO NEUROSCIENCE LETTERS LA English DT Article ID PROTEIN-KINASE-C; DISEASE; PHOSPHORYLATION; TRANSLOCATION; BRAIN; BINDING; CORTEX; HETEROGENEITY; POTENTIATION; FIBROBLASTS AB Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.003). After 3 weeks of lithium treatment, AD patients had significantly less membrane-associated PKC alpha (P < 0.002), epsilon (P < 0.003), and zeta (P < 0.001) than normals. This is the first report of a difference in PKC in blood cells between AD and control subjects. These findings appear to indicate that some PKC isozymes may be differentially regulated in AD versus elderly controls, at least as evidenced in this peripheral cellular system. RP NIH, CTR CLIN, 9000 ROCKVILLE PIKE, BLDG 10, RM 3D41, BETHESDA, MD 20892 USA. NR 36 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 12 PY 1993 VL 162 IS 1-2 BP 187 EP 191 DI 10.1016/0304-3940(93)90592-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA MH359 UT WOS:A1993MH35900048 PM 8121626 ER PT J AU FAUCI, AS AF FAUCI, AS TI MULTIFACTORIAL NATURE OF HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE - IMPLICATIONS FOR THERAPY SO SCIENCE LA English DT Article ID TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; B-CELL ACTIVATION; IMMUNE-DEFICIENCY SYNDROME; GROWTH-FACTOR-BETA; FOLLICULAR DENDRITIC CELLS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLASMODIUM-FALCIPARUM MALARIA; AIDS-RELATED LYMPHADENOPATHY; FACTOR-ALPHA PRODUCTION AB The immunopathogenic mechanisms underlying human immunodeficiency virus (HIV) disease are extremely complex; the disease process is multifactorial with multiple overlapping phases. Viral burden is substantial and viral replication occurs throughout the entire course of HIV infection. Inappropriate immune activation and elevated secretion of certain cytokines compound the pathogenic process. Profound immunosuppression ultimately occurs together with a disruption of the microenvironment of the immune system, which is probably unable to regenerate spontaneously. Thus, therapeutic strategies in HIV disease must not be unidimensional, but rather must be linked to the complex pathogenic components of the disease and must address where feasible each of the recognized pathogenic processes for the possibility of therapeutic intervention. RP FAUCI, AS (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 250 TC 766 Z9 771 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 12 PY 1993 VL 262 IS 5136 BP 1011 EP 1018 DI 10.1126/science.8235617 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MG187 UT WOS:A1993MG18700024 PM 8235617 ER PT J AU SALK, J BRETSCHER, PA SALK, PL CLERICI, M SHEARER, GM AF SALK, J BRETSCHER, PA SALK, PL CLERICI, M SHEARER, GM TI PROTECTION FROM HIV-INFECTION OR AIDS - RESPONSE SO SCIENCE LA English DT Article ID T-CELLS C1 UNIV SASKATCHEWAN,DEPT MICROBIOL,SASKATOON S7N 0W0,SASKATCHEWAN,CANADA. JONAS SALK FDN,LA JOLLA,CA 92037. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP SALK, J (reprint author), SALK INST BIOL STUDIES,SAN DIEGO,CA 92138, USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 12 PY 1993 VL 262 IS 5136 BP 1075 EP 1076 DI 10.1126/science.262.5136.1075 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MG187 UT WOS:A1993MG18700043 PM 17782052 ER PT J AU OLDEN, K AF OLDEN, K TI CLASHING CULTURES - BRINGING SCIENCE BACK TO THE NEIGHBORHOOD SO SCIENCE LA English DT Editorial Material RP OLDEN, K (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 12 PY 1993 VL 262 IS 5136 BP 1116 EP 1116 DI 10.1126/science.8235631 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MG187 UT WOS:A1993MG18700058 PM 8235631 ER PT J AU BANERJEE, R GINSBURG, E VONDERHAAR, BK AF BANERJEE, R GINSBURG, E VONDERHAAR, BK TI CHARACTERIZATION OF A MONOCLONAL-ANTIBODY AGAINST HUMAN PROLACTIN RECEPTORS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-BREAST CANCER; EPIDERMAL GROWTH-FACTOR; TUMOR-ASSOCIATED ANTIGENS; MOUSE MAMMARY-GLAND; ATHYMIC NUDE-MICE; CARCINOEMBRYONIC ANTIGEN; DNA-SYNTHESIS; CELLS; BINDING; PURIFICATION AB Tamoxifen is the first line of therapy for most human breast cancers. It not only works through the estrogen receptor but also can directly affect the binding of prolactin to its receptor. To define this latter mechanism, the nature of the prolactin receptor needs to be clearly defined. Monoclonal antibody (MAb) B6.2, an IgG1 raised against a membrane-enriched fraction from metastatic human breast cancer cells, was as effective as polyclonal anti-prolactin receptor antibody in inhibiting the binding of prolactin to membranes from human tissue and to T47D human breast cancer cells. Control MAbs, MOPC-21 and the anti-NCA B1.1 MAb, had no effect on binding. Epidermal growth-factor receptors on these same cells were unaffected by B6.2. Prolactin-induced growth of the T47D cells was blocked by addition of B6.2 to the media while the control antibodies were without effect. Specific binding of B6.2 to the cells was completely inhibited by prolactin. Binding of both prolactin and B6.2 was inhibited by growing the T47D cells in the presence of tunicamycin A1 under conditions where protein synthesis was not affected but glycosylation of proteins was. An affinity column of B6.2 was used to purify its antigen from T47D cells. The primary purification product, a M(r) 90,000 protein, specifically bound the lactogenic hormones human prolactin, human growth hormone and ovine prolactin but not the somatogenic hormone, bovine growth hormone and was precipitated by the polyclonal anti-prolactin receptor antibody but not by control MAbs. When tryptic and V8 digests of the B6.2 antigen and purified prolactin receptors were compared, identical electrophoretic profiles were obtained. Mouse 3T3 cells, when stably transfected with the gene for the long form of the human prolactin receptor, reacted with B6.2 and polyclonal anti-prolactin receptor antibody. Parental 3T3 cells, devoid of prolactin receptors, were negative for all antibodies tested. Thus, MAb B6.2 provides a useful tool for further studies on purification and characterization of these receptors from human tissues and may provide new insights into treatment for breast cancer. (C) 1993 Wiley-Liss, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B56,BETHESDA,MD 20892. NR 37 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1993 VL 55 IS 5 BP 712 EP 721 DI 10.1002/ijc.2910550503 PG 10 WC Oncology SC Oncology GA MH172 UT WOS:A1993MH17200002 PM 7503956 ER PT J AU WEST, S HILDESHEIM, A DOSEMECI, M AF WEST, S HILDESHEIM, A DOSEMECI, M TI NONVIRAL RISK-FACTORS FOR NASOPHARYNGEAL CARCINOMA IN THE PHILIPPINES - RESULTS FROM A CASE-CONTROL STUDY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SQUAMOUS-CELL CANCERS; SALTED FISH; FORMALDEHYDE; EXPOSURE AB In a case-control study of NPC conducted in the Philippines, 104 predominantly non-Chinese (< 10% ethnically Chinese) cases of nasopharyngeal carcinoma (NPC) and 205 hospital and community controls were recruited. Risk factor information was obtained through personal interview. The occupational history of each subject was reviewed ''blind'' by an industrial hygienist to determine estimates of exposure to formaldehyde, solvents, dusts, exhaust and pesticides. After control for confounding, subjects who were first exposed to formaldehyde 25 or more years prior to diagnosis/interview or who were first exposed before the age of 25 were found, in relation to those never exposed, to be at a 4.0-fold excess risk of disease. Similarly, those first exposed to dust and/or exhaust 35 or more years prior to diagnosis/interview were at a 4.4-fold excess risk of disease and those first exposed before the age of 20 were at a 3.5-fold excess risk of disease. Salted fish consumption was not associated with risk, while consumption of processed meats protected against NPC. Smoking was positively associated with NPC, but only when cases were compared to community controls. Relative to non-smokers, subjects reporting more than 30 years of smoking were at an adjusted 7.2-fold excess risk of disease. Herbal medicine use and burning of anti-mosquito coils were both independently associated with risk of NPC, with ever-users of herbal medicines being at a 2.5-fold excess risk of disease and those reporting daily use of anti-mosquito coils being at a 5.9-fold excess risk of disease relative to never users. Exposure to solvents, pesticides, or use of betel nuts were not associated with NPC risk. (C) 1993 Wiley-Liss, Inc. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21205. NR 18 TC 70 Z9 72 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1993 VL 55 IS 5 BP 722 EP 727 DI 10.1002/ijc.2910550504 PG 6 WC Oncology SC Oncology GA MH172 UT WOS:A1993MH17200003 PM 7503957 ER PT J AU PREWITT, TW LUBENSKY, IA POGREBNIAK, HW PASS, HI AF PREWITT, TW LUBENSKY, IA POGREBNIAK, HW PASS, HI TI ORTHOTOPIC IMPLANTATION OF MESOTHELIOMA IN THE PNEUMONECTOMIZED IMMUNE-DEFICIENT RAT - A MODEL FOR INNOVATIVE THERAPIES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID CANCER RP PREWITT, TW (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 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 NOV 11 PY 1993 VL 55 IS 5 BP 877 EP 880 PG 4 WC Oncology SC Oncology GA MH172 UT WOS:A1993MH17200029 PM 8244586 ER PT J AU BRESSLER, SL COPPOLA, R NAKAMURA, R AF BRESSLER, SL COPPOLA, R NAKAMURA, R TI EPISODIC MULTIREGIONAL CORTICAL COHERENCE AT MULTIPLE FREQUENCIES DURING VISUAL TASK-PERFORMANCE SO NATURE LA English DT Article ID OSCILLATORY NEURONAL RESPONSES; CORTEX; CAT; SYNCHRONIZATION; MONKEY; PATTERNS; STRIATE AB THE way in which the brain integrates fragmentary neural events at multiple locations to produce unified perceptual experience and behaviour is called the binding problem1,2. Binding has been proposed to involve correlated activity at different cortical sites during perceptuomotor behaviour3-5, particularly by synchronization of narrow-band oscillations in the gamma-frequency range (30-80 Hz)6,7. In the rabbit olfactory system, inhalation induces increased gamma-correlation between sites in olfactory bulb and cortex8. In the cat visual system, coherent visual stimuli increase gamma-correlation between sites in both the same and different visual cortical areas9-12. In monkeys, some groups have found that gamma-ocillations transiently synchronize within striate cortex13, superior temporal sulcus14 and somatosensorimotor cortex15,16. Others have report that visual stimuli produce increased broad-band power, but not gamma-oscillations, in several visual cortical areas17,18. But the absence of narrow-band oscillations in itself does not disprove inter-regional synchronization, which may be a broad-band phenomenon. We now describe episodes of increased broad-band coherence among local field potentials from sensory, motor and higher-order cortical sites of macaque monkeys performing a visual discrimination task. Widely distributed sites become coherent without involving other interverting sites. Spatially selective multiregional cortical binding, in the form of broad-band synchronization, may thus play a role in primate perceptuomotor behaviour. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP BRESSLER, SL (reprint author), FLORIDA ATLANTIC UNIV,CTR COMPLEX SYST,BOCA RATON,FL 33431, USA. NR 26 TC 337 Z9 341 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 11 PY 1993 VL 366 IS 6451 BP 153 EP 156 DI 10.1038/366153a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MG216 UT WOS:A1993MG21600056 PM 8232553 ER PT J AU EKBOM, A MCLAUGHLIN, JK NYREN, O AF EKBOM, A MCLAUGHLIN, JK NYREN, O TI PANCREATITIS AND THE RISK OF PANCREATIC-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI,BETHESDA,MD 20892. RP EKBOM, A (reprint author), UNIV UPPSALA,S-75185 UPPSALA,SWEDEN. NR 2 TC 18 Z9 18 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 11 PY 1993 VL 329 IS 20 BP 1502 EP 1502 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MF292 UT WOS:A1993MF29200024 PM 8413467 ER PT J AU TANIZAWA, A KOHN, KW POMMIER, Y AF TANIZAWA, A KOHN, KW POMMIER, Y TI INDUCTION OF CLEAVAGE IN TOPOISOMERASE-I C-DNA BY TOPOISOMERASE-I ENZYMES FROM CALF THYMUS AND WHEAT-GERM IN THE PRESENCE AND ABSENCE OF CAMPTOTHECIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SIMIAN VIRUS-40 DNA; CELL-LINE; SV40 DNA; EUKARYOTIC TOPOISOMERASE; RECOGNITION SITES; LUNG-CANCER; SEQUENCE; BACTERIOPHAGE-T4; SPECIFICITY; BREAKAGE AB In this study, we further examined the sequence selectivity of camptothecin in mammalian topoisomerase I cDNA from human and Chinese hamster. In the absence of camptothecin, almost all the bases at the 3'-terminus of cleavage sites are T for calf thymus and wheat germ topolsomerase 1. In addition, wheat germ topoisomerase I exhibits preference for C (or not T) at -3 and for T at -2 position. As for camptothecin-stimulated cleavage with topoisomerase 1, G (or not T) at + 1 is an additional strong preference. This sequence selectivity of camptothecin is similar to that previously found in SV40 DNA, suggesting that camptothecin preferentially interacts with topolsomerase 1-mediated cleavage sites where G is the base at the 5'-terminus. These results support the stacking model of camptothecin (Jaxel et al. (1991) J. Biol. Chem. 266, 20418 - 20423). Comparison of calf thymus and wheat germ topoisomerase I-mediated cleavage sites in the presence of camptothecin shows that many major cleavage sites are similar. However, the relative intensities are often different. One of the differences was attributable to a bias at position - 3 where calf thymus topoisomerase I prefers G and wheat germ topoisomerase I prefers C. This difference may explain the unique patterns of cleavage sites induced by the two enzymes. Sequencing analysis of camptothecin-stimulated cleavage sites in the surrounding regions of point mutations in topolsomerase I cDNA, which were found in camptothecin-resistant cell lines, reveals no direct relationship between DNA cleavage sites in vitro and mutation sites. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 41 TC 53 Z9 54 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 NOV 11 PY 1993 VL 21 IS 22 BP 5157 EP 5166 DI 10.1093/nar/21.22.5157 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ262 UT WOS:A1993MJ26200024 PM 8255771 ER PT J AU ECKERT, KA KUNKEL, TA AF ECKERT, KA KUNKEL, TA TI FIDELITY OF DNA-SYNTHESIS CATALYZED BY HUMAN DNA-POLYMERASE ALPHA AND HIV-1 REVERSE-TRANSCRIPTASE - EFFECT OF REACTION PH SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MUTATIONAL SPECIFICITY; CYTOPLASMIC PH; BASE-PAIRS; MECHANISM; INVITRO; FRAGMENT; GROWTH; GAMMA AB The accuracy of DNA synthesis catalyzed by the Thermus aquaticus DNA polymerase and the 3'-5' exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I varies as a function of reaction pH (Eckert,K.A. and Kunkel,T.A. (1990) Nucleic Acids Res. 18, 3739-3744; Eckert,K.A. and Kunkel,T.A. (1993) J. Biol. Chem. 268, 13462 - 13471). In the current study, we demonstrate that the fidelity of human DNA polymerase alpha increases 10-fold when the pH of the in vitro synthesis reaction is lowered from pH 8.6 to pH 6.1 (37-degrees-C), as determined using a base substitution reversion assay to score polymerase errors within the lacZalpha gene of bacteriophage M13mp2. Similarly, the base substitution fidelity of DNA-dependent DNA synthesis by the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was improved nine-fold at pH 6.5 relative to pH 8.0 (37-degrees-C). A detailed comparison of HIV-1 RT error specificity at neutral and low pH in a lacZalpha forward mutation assay revealed that low pH suppresses both mispairing-mediated and misalignment-mediated mutations; however, the characteristic HIV-1 RT pattern of mutational hotspots at homopolymeric sequences is retained at the lower pH. Consistent with the presumption that these mutations result, in part, from increased termination of DNA synthesis within the hotspot sequences relative to other homopolymeric sequences, the HIV-1 RT termination pattern during processive DNA synthesis is not altered by low pH. The HIV-1 RT results are in agreement with our previous hypothesis that the observed increase in polymerase fidelity at low pH results from a decreased efficiency of continuing DNA synthesis from premutational DNA intermediates. C1 NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 26 TC 45 Z9 46 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1993 VL 21 IS 22 BP 5212 EP 5220 DI 10.1093/nar/21.22.5212 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ262 UT WOS:A1993MJ26200032 PM 7504813 ER PT J AU BRUDER, JT HEIDECKER, G TAN, TH WESKE, JC DERSE, D RAPP, UR AF BRUDER, JT HEIDECKER, G TAN, TH WESKE, JC DERSE, D RAPP, UR TI ONCOGENE ACTIVATION OF HIV-LTR-DRIVEN EXPRESSION VIA THE NF-KAPPA-B BINDING-SITES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; P72-74 RAF-1 KINASE; NIH 3T3 CELLS; PROTEIN-KINASE; SIGNAL TRANSDUCTION; REL ONCOGENE; T-CELLS; PHOSPHORYLATION; TRANSCRIPTION; GENE AB The Raf-1 proto-oncogene product is a highly regulated serine/threonine kinase that functions in signal transduction downstream from growth factor receptors and upstream from nuclear proto-oncogene products. Using a transient cotransfection assay we have found that activated Raf-1 activates expression from the HIV-LTR. Analysis of a series of 5' deletion and point mutations revealed the NF-kappaB motifs as the Raf-responsive element in the HIV-LTR. Moreover, Raf-BXB activated expression from heterologous promoters driven by the HIV NF-kappaB binding sites. In addition to Raf, we show that v-Src, v-H-Ras and v-Mos activate HIV-LTR expression through the NF-kappaB binding sites and v-H-Ras-induced HIV-LTR expression is mediated by Raf-1. These findings may have implications for the involvement of the cellular homologues of these oncogenes in the switch from latent to productive infection by HIV in response to T-cell activation. C1 PRI DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,VIRAL PATHOL SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NCI NIH HHS [N0I-CO-74102] NR 44 TC 33 Z9 34 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 NOV 11 PY 1993 VL 21 IS 22 BP 5229 EP 5234 DI 10.1093/nar/21.22.5229 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ262 UT WOS:A1993MJ26200034 PM 8255780 ER PT J AU GBENLE, GO AF GBENLE, GO TI CHARACTERIZATION OF A FILTERABLE 3'-NUCLEOTIDASE OF LEISHMANIA-DONOVANI SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE 3'-NUCLEOTIDASE; FILTERABLE ENZYME; PLASMA MEMBRANE; NUCLEOSIDE SUPPLY; (LEISHMANIA-DONOVANI) ID LOCALIZATION; MEMBRANE AB A plasma membrane 3'-nucleotidase (3'-ribonucleotide phosphohydrolase, EC 3.1.3.6) having a apparent subunit molecular mass of 38 kDa but filtrable through a Centriprep-10 microconcentrator (Amicon) membrane was purified from Leishmania donovani promastigotes. The enzyme activity has an optimum at pH around 7.5. EDTA strongly inhibited the enzyme activity which was fully restored only by Co2+, from various metal ions added. Citrate ions, Zn2+ or dithiothreitol were also strongly inhibitory. The enzyme is apparently located on the inner side of the parasite plasma membrane. The substrate specificity and kinetics of the filtrable enzyme are similar to those of the non-filtrable outer-surface-membrane-bound 3'-nucleotidase reported by Gbenle and Dwyer (Gbenle, G.O. and Dwyer, D.M. (1992) Biochem. J. 285, 41-46). Therefore, it is suggested that both enzymes are implicated in the supply of nucleosides to the parasite. C1 NIH,CELL BIOL & IMMUNOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. RP GBENLE, GO (reprint author), UNIV LAGOS,COLL MED,DEPT BIOCHEM,PMB 12003,LAGOS,NIGERIA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD NOV 10 PY 1993 VL 1203 IS 1 BP 162 EP 167 DI 10.1016/0167-4838(93)90051-R PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ424 UT WOS:A1993MJ42400023 PM 8218386 ER PT J AU THEODOROPOULOS, DS KRASNEWICH, D KAISERKUPFER, MI GAHL, WA AF THEODOROPOULOS, DS KRASNEWICH, D KAISERKUPFER, MI GAHL, WA TI CLASSIC NEPHROPATHIC CYSTINOSIS AS AN ADULT DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NERVOUS-SYSTEM INVOLVEMENT; AGE 10 YEARS; CYSTEAMINE; COMPLICATIONS; INSUFFICIENCY; CHILDREN; PATIENT AB Objective.-To delineate the clinical characteristics of infantile nephropathic cystinosis in adult patients who have undergone renal transplantation. Design.-Case series. Setting.-Clinical research unit. Patients.-All 36 adult patients with nephropathic cystinosis referred to the National Institutes of Health. Outcome Measures.-Longevity, growth, renal allograft survival, visual acuity, endocrine insufficiency, myopathy and swallowing dysfunction, cerebral calcifications, and occupational status. Results.-Of the 36 patients, seven were dead, five with functioning allografts. The 1-year and 5-year graft survival rates for 30 cadaveric allografts were 90% and 75%, respectively. The patients' mean height and weight were severely retarded. Five patients were legally blind, and three others had severely impaired vision in one eye. Thirty-one (86%) of 36 patients required thyroid hormone replacement therapy. One third had a distal myopathy, and 21 had moderate to severe swallowing abnormalities. Eight patients had cerebral calcifications on computed tomographic scan. Despite these complications, the sighted patients engaged in a normal variety of occupations. Only 11 patients were receiving adequate cystine-depleting therapy with cysteamine (mercaptamine) or phosphocysteamine. Conclusions.-Adult patients with nephropathic cystinosis suffer serious complications of the disease. C1 NIH,CTR CLIN,INTERINST MED GENET PROGRAM,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. NR 28 TC 50 Z9 53 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 1993 VL 270 IS 18 BP 2200 EP 2204 DI 10.1001/jama.270.18.2200 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ME816 UT WOS:A1993ME81600031 PM 8411603 ER PT J AU LIU, KL MILES, HT FRAZIER, J SASISEKHARAN, V AF LIU, KL MILES, HT FRAZIER, J SASISEKHARAN, V TI A NOVEL DNA DUPLEX - A PARALLEL-STRANDED DNA HELIX WITH HOOGSTEEN BASE-PAIRING SO BIOCHEMISTRY LA English DT Article ID DERIVATIVES; ACID); RAMAN AB We show here for the first time that a stable parallel double helix with Hoogsteen pairing can exist independently of the triple helix of which it is a component part. The experiments employ DNA oligonucleotides with mixed sequences of normal bases. These duplexes are distinct from previously reported ribopolynucleotide helices containing bulky substituents which prevent Watson-Crick pairing as well as from parallel duplexes with Dronohue, or reversed Watson-Crick, pairing. Stoichiometry is established by mixing curves and gel electrophoresis. T(m) depends linearly upon pH, increasing with acidity because of the need to protonate N3 of C. The T(m) of the 20-mer studied here is 52-degrees-C at pH 5.2 and 0.1 M NaCl. At pH above 6, the molecule rearranges to form an antiparallel duplex with imperfect Watson-Crick pairing and loops, and the T(m) is then independent of pH. The CD spectrum of the parallel duplex is very similar to that of the corresponding triple helix but quite different from that of the Watson-Crick helix. The infrared spectrum in the double bond region closely resembles that of the triple helix but, as with the CD, is quite different from that of the Watson-Crick duplex. The infrared spectra of the duplex and triple helix are also nearly identical in the region from 800 to 1000 cm-1, which is sensitive to backbone conformation. The only symmetry element present is a pseudorotational axis coincident with the helix axis of the parallel duplex as well as with the axis of the corresponding triple helix. We suggest that structural and spectroscopic properties of the triple helix are determined by the Hoogsteen-paired strands and not by the Watson-Crick-paired component strands. RP LIU, KL (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 45 TC 78 Z9 79 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 9 PY 1993 VL 32 IS 44 BP 11802 EP 11809 DI 10.1021/bi00095a008 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF820 UT WOS:A1993MF82000008 PM 8218251 ER PT J AU JONES, DNC BOWEN, WD PORTOGHESE, PS HOLTZMAN, SG AF JONES, DNC BOWEN, WD PORTOGHESE, PS HOLTZMAN, SG TI DELTA-OPIOID RECEPTOR ANTAGONISTS ATTENUATE MOTOR-ACTIVITY INDUCED BY AMPHETAMINE BUT NOT COCAINE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE AMPHETAMINE; COCAINE; MOTOR ACTIVITY; DELTA-OPIOID RECEPTOR ANTAGONIST; OPIOID-DOPAMINE INTERACTION ID DELTA-OPIOID RECEPTORS; FREELY MOVING RATS; DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; NALTRINDOLE 5'-ISOTHIOCYANATE; DIFFERENTIAL ANTAGONISM; INDUCED HYPERACTIVITY; INVIVO MICRODIALYSIS; PLACE PREFERENCE; OPIATE AGONISTS AB Naloxone and naltrindole attenuate the locomotor response to amphetamine, implicating delta-opioid receptors in the opioid-antagonist/amphetamine interaction. To determine the role of delta-opioid receptor subtypes in this phenomenon, rats were pretreated with the following selective antagonists administered intracisternally: naltrindole, [D-Ala(2),Leu(5),Cys(6)]enkephalin (DALCE, delta(1) receptor selective), naltrindole-5'-isothiocyanate (delta(2) receptor selective). Cumulative dose-response curves to amphetamine were constructed (saline, 0.1, 0.4, 1.6 and 6.4 mg/kg s.c.), with injections every 30 min. Naltrindole was also tested against cumulative doses of cocaine (saline, 3.0, 10, 30 and 56 mg/kg i.p.). Gross and fine motor activity were recorded for 20 min, commencing 10 min postinjection. Amphetamine and cocaine dose dependently increased both gross and fine movements. Naltrindole (10 mu g) attenuated the gross but not fine activity response to amphetamine, but 10 or 30 mu g failed to influence the response to cocaine. Naltrindole-5'-isothiocyanate (30 mu g) attenuated slighty but significantly the gross activity response to amphetamine, whereas DALCE (30 mu g) was without effect. However, a combination of 10 mu g each of DALCE and naltrindole-5'-isothiocyanate markedly attenuated the amphetamine-induced increases in gross movements without altering fine activity. These data provide further evidence for the involvement of delta-opioid receptors in the modulation of behavioral effects of amphetamine; both delta(1)- and delta(2)-opioid receptors appear to play a role. The differential effects of opioid antagonists on locomotor activity stimulated by amphetamine and cocaine suggests differences in the mechanism of action of these drugs not previously appreciated. C1 EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322. NIDDK,RECEPTOR BIOCHEM & PHARMACOL UNIT,DRUG DESIGN & SYNTH SECT,MED CHEM LAB,BETHESDA,MD. UNIV MINNESOTA,COLL PHARM,DEPT MED CHEM,MINNEAPOLIS,MN 55455. FU NIDA NIH HHS [KO5 DA00008, DA00541] NR 60 TC 35 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 9 PY 1993 VL 249 IS 2 BP 167 EP 177 DI 10.1016/0014-2999(93)90429-L PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MG154 UT WOS:A1993MG15400006 PM 8287898 ER PT J AU GOSO, C EVANGELISTA, S TRAMONTANA, M MANZINI, S BLUMBERG, PM SZALLASI, A AF GOSO, C EVANGELISTA, S TRAMONTANA, M MANZINI, S BLUMBERG, PM SZALLASI, A TI TOPICAL CAPSAICIN ADMINISTRATION PROTECTS AGAINST TRINITROBENZENE SULFONIC ACID-INDUCED COLITIS IN THE RAT SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE EXPERIMENTAL COLITIS; CAPSAICIN; RESINIFERATOXIN BINDING; VANILLOID RECEPTOR ID GENE-RELATED PEPTIDE; DELAYED-TYPE HYPERSENSITIVITY; GASTRIC-MUCOSAL PROTECTION; SENSITIVE AFFERENT NERVES; SUBSTANCE-P; CALCITONIN; RESINIFERATOXIN; ANTAGONIST; NEURONS; RELEASE AB We used the [H-3]resiniferatoxin binding assay to demonstrate for the first time the existence of vanilloid receptors in the rat colon and to explore their expression during trinitrobenzene sulfonic acid-induced colitis. Membranes obtained from control colon bound [H-3]resiniferatoxin with an affinity of 3 nM; the receptor density was 450 fmol/mg protein or 9 fmol/mg wet weight. Capsaicin and capsazepine, a competitive antagonist of capsaicin, inhibited specific resiniferatoxin binding with K-i values of 3 mu M and 0.1 mu M, respectively. Trinitrobenzene sulfonic acid induced a very rapid ulceration in the colon: 1 h after treatment 90% of the colon showed ulcerative damage. Coadministration of 640 mu M capsaicin diminished the ulcerative effect of trinitrobenzene sulfonic acid to 64% when examined 1 h after trinitrobenzene sulfonic acid challenge; however, this protective action was lost 23 h later. Colon samples obtained 4 h, 24 h, and 1 week after trinitrobenzene sulfonic acid challenge bound resiniferatoxin, capsaicin, and capsazepine with affinities similar to those of control samples. The receptor density remained at an essentially constant level when expressed in fmol/mg protein but, in keeping with the increased wet weights, showed a reduction when expressed in fmol/mg wet weight. We conclude that acute capsaicin administration protects against the ulcerative action of trinitrobenzene sulfonic acid, most likely via the release of protective neuropeptides from capsaicin-sensitive nerve endings. The loss of this protective action is presumably due to a depletion of the protective neuropeptides rather than to a loss of vanilloid (capsaicin) receptors. C1 MENARINI SUD,DEPT PHARMACOL,ROME,ITALY. MALESCI PHARMACEUT,DEPT PHARMACOL,FLORENCE,ITALY. NCI,BETHESDA,MD 20892. NR 33 TC 47 Z9 49 U1 0 U2 0 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 NOV 9 PY 1993 VL 249 IS 2 BP 185 EP 190 DI 10.1016/0014-2999(93)90431-G PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MG154 UT WOS:A1993MG15400008 PM 8287899 ER PT J AU SUKHOV, RR WALKER, LC RANCE, NE PRICE, DL YOUNG, WS AF SUKHOV, RR WALKER, LC RANCE, NE PRICE, DL YOUNG, WS TI VASOPRESSIN AND OXYTOCIN GENE-EXPRESSION IN THE HUMAN HYPOTHALAMUS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE BASAL FOREBRAIN; PARAVENTRICULAR NUCLEUS; IN-SITU HYBRIDIZATION HISTOCHEMISTRY; SUPRACHIASMATIC NUCLEUS; SUPRAOPTIC NUCLEUS ID MESSENGER RIBONUCLEIC-ACIDS; HUMAN-MEMORY PROCESSES; HYBRIDIZATION HISTOCHEMISTRY; SUPRACHIASMATIC NUCLEUS; INSITU HYBRIDIZATION; HUMAN-BRAIN; MAGNOCELLULAR NEURONS; CHEMICAL MESSENGERS; ALZHEIMERS-DISEASE; RNA AB We studied the distribution of messenger ribonucleic acids coding for vasopressin and oxytocin in the human hypothalamus by means of hybridization histochemistry. Numerous large and medium-sized neurons contain vasopressin messenger ribonucleic acid in the paraventricular nucleus, supraoptic nucleus, and accessory magnocellular nucleus. Small, lightly labeled vasopressin neurons also were detected in the suprachiasmatic nucleus. In addition, a relatively sparse band of mostly ovoid, medium-sized vasopressin neurons mingle with unlabeled neurons of the lateral hypothalamic area; these cells extend dorsoventrally from the region ventral to the stria terminalis to the ventrolateral hypothalamus, sometimes transgressing the boundaries of nearby nuclei. We did not detect vasopressin gene expression in neurons of the bed nucleus of the stria terminalis proper, although some of the dorsal-most labeled neurons of the lateral hypothalamus extend into the region of the caudal bed nucleus. Some lateral hypothalamic neurons also encroach upon other extrahypothalamic structures, such as the zona incerta. The nucleus basalis of Meynert complex was, with only rare exceptions, devoid of cells containing vasopressin messenger ribonucleic acid. Oxytocin messenger ribonucleic acid is found in the supraoptic nucleus, paraventricular nucleus, accessory magnocellular nucleus and, less frequently, in neurons of the lateral hypothalamus. In the hypothalamic magnocellular nuclei, oxytocin neurons are somewhat smaller than vasopressin neurons. Vasopressin cells outnumber oxytocin cells in the supraoptic nucleus, but their numbers are comparable in the paraventricular nucleus. As with vasopressin neurons, lateral hypothalamic oxytocin cells loosely span several diencephalic nuclei and encroach occasionally upon adjacent regions. These results confirm that the organization of vasopressin and oxytocin neurons in the human hypothalamus is largely comparable to that in nonhuman species and demonstrate the utility of hybridization histochemistry for elucidating the chemoarchitecture of the human brain. (C) 1993 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,558 ROSS RES BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205. UNIV ARIZONA,COLL MED,DEPT PATHOL,TUCSON,AZ 85721. UNIV ARIZONA,COLL MED,DEPT NEUROL,TUCSON,AZ 85721. UNIV ARIZONA,COLL MED,DEPT ANAT,TUCSON,AZ 85721. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. RI Young, W Scott/A-9333-2009; Walker, L/J-6541-2015 OI Young, W Scott/0000-0001-6614-5112; Walker, L/0000-0001-9166-3261 FU NINDS NIH HHS [NS 07179, NS 20471, NS AG 05146] NR 48 TC 18 Z9 18 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 8 PY 1993 VL 337 IS 2 BP 295 EP 306 DI 10.1002/cne.903370210 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA ME052 UT WOS:A1993ME05200009 PM 8277003 ER PT J AU OZAKI, N DUNCAN, WC JOHNSON, KA WEHR, TA AF OZAKI, N DUNCAN, WC JOHNSON, KA WEHR, TA TI DIURNAL-VARIATIONS OF SEROTONIN AND DOPAMINE LEVELS IN DISCRETE BRAIN-REGIONS OF SYRIAN-HAMSTERS AND THEIR MODIFICATION BY CHRONIC CLORGYLINE TREATMENT SO BRAIN RESEARCH LA English DT Article DE CIRCADIAN RHYTHM; CLORGYLINE; SEROTONIN; DOPAMINE; SUPRACHIASMATIC NUCLEUS; RAPHE NUCLEI; SYRIAN HAMSTER ID SUPRACHIASMATIC NUCLEI; CIRCADIAN-RHYTHM; LOCOMOTOR-ACTIVITY; RAPHE NUCLEI; RAT-BRAIN; LOCALIZATION; PROJECTIONS; RECEPTORS; AGONISTS; BINDING AB In Syrian hamsters, chronic administration of the type A monoamine oxidase inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the circadian rhythm of wheel running, and changes the intensity-response curve for phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also decreases hypothalamic and peritoneal temperatures, particularly during the rest phase of the activity-rest cycle. To help identify monoamines that may mediate CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal variation was detected in all regions in saline-treated animals; for DA, no diurnal variation was detected in any region. In all regions. 5-HT levels and, to a lesser extent, DA levels were higher after CLG treatment. The acrophase of the 5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment, while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial preoptic area, and median raphe nuclei was no longer detectable after chronic CLG-treatment. The phase-delay induced by CLG treatment in the daily rhythm of serotonin levels in the SCN, which functions as a circadian pacemaker, may be an important mechanism underlying the drug's capacity to slow the intrinsic rhythm of the pacemaker and to phase-delay behavioral rhythms that are under its control. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 43 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 5 PY 1993 VL 627 IS 1 BP 41 EP 48 DI 10.1016/0006-8993(93)90746-A PG 8 WC Neurosciences SC Neurosciences & Neurology GA ME270 UT WOS:A1993ME27000006 PM 8293303 ER PT J AU SCHEFFNER, M HUIBREGTSE, JM VIERSTRA, RD HOWLEY, PM AF SCHEFFNER, M HUIBREGTSE, JM VIERSTRA, RD HOWLEY, PM TI THE HPV-16 E6 AND E6-AP COMPLEX FUNCTIONS AS A UBIQUITIN-PROTEIN LIGASE IN THE UBIQUITINATION OF P53 SO CELL LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; N-END RULE; RETINOBLASTOMA GENE-PRODUCT; CELLULAR TUMOR-ANTIGEN; CARRIER PROTEIN; SV40-TRANSFORMED CELLS; INVITRO MUTAGENESIS; HUMAN KERATINOCYTES; CONJUGATING ENZYME; TRANSFORMED-CELLS AB The ubiquitin-dependent proteolytic pathway plays a major role in selective protein degradation. Ubiquitination of proteins requires the sequential action of the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 18 utilize this cellular proteolytic system to target the tumor suppressor protein p53. The HPV E6 oncoprotein binds to a cellular protein of 100 kd, termed E6-associated protein (E6-AP). The E6-E6-AP complex specifically interacts with p53, resulting in the rapid ubiquitin-dependent degradation of p53. Here we report the purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of p53. The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6. C1 UNIV WISCONSIN,DEPT HORT,MADISON,WI 53706. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RI Scheffner, Martin/K-2940-2012; Tang, Amy/L-3226-2016 OI Scheffner, Martin/0000-0003-2229-0128; Tang, Amy/0000-0002-5772-2878 NR 57 TC 1557 Z9 1594 U1 8 U2 46 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 5 PY 1993 VL 75 IS 3 BP 495 EP 505 DI 10.1016/0092-8674(93)90384-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF830 UT WOS:A1993MF83000012 PM 8221889 ER PT J AU BECERRA, SP PALMER, I KUMAR, A STEELE, F SHILOACH, J NOTARIO, V CHADER, GJ AF BECERRA, SP PALMER, I KUMAR, A STEELE, F SHILOACH, J NOTARIO, V CHADER, GJ TI OVEREXPRESSION OF FETAL HUMAN PIGMENT EPITHELIUM-DERIVED FACTOR IN ESCHERICHIA-COLI - A FUNCTIONALLY ACTIVE NEUROTROPHIC FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEASE INHIBITORY ACTIVITY; NEURITE-PROMOTING FACTOR; NERVE GROWTH-FACTOR; HUMAN ALPHA-1-ANTICHYMOTRYPSIN; CDNA SEQUENCE; BINDING; DIFFERENTIATION; CHYMOTRYPSIN; EXPRESSION; PROTEINS AB Pigment epithelium-derived factor (PEDF) is a neurotrophic protein present in low amounts in conditioned medium of cultured fetal human retinal pigment epithelial cells. Recently, the PEDF cDNA has been cloned from a fetal human cDNA library, and its derived amino acid sequence identified it as a member of the serine protease inhibitor (serpin) supergene family (Steele, F. R., Chader, G. J., Johnson, L. V., and Tombran-Tink, J. (1993) Proc. Natl. Acad, Sci. U. S. A. 90, 1526-1530). We have prepared recombinant expression constructs from the fetal human PEDF cDNA and obtained milligram amounts of biologically active PEDF from Escherichia coli. The full-length open reading frame (Met1-Pro418) and a truncated form (Asp44- Pro41) were used in our constructs. Induction from a vector containing the truncated PEDF version, named pEV-BH, produced a protein (BH) of expected size (M(r) 42,800) associated with inclusion bodies, which contained 25-40% of expressed protein. After solubilization, BH was highly purified by gel filtration and cation exchange chromatography. The NH2-terminal sequence of the purified protein matched that of the pEV-BH construct. We have conducted neurite outgrowth assays in a human retinoblastoma Y-79 cell culture system. Recombinant PEDF (BH) demonstrated neurotrophic activity, as reported for the native PEDF. Thus, unfolded and refolded in vitro BH retained a potent biological activity. In parallel experiments, protease inhibition assays were performed. Recombinant PEDF did not have an effect on trypsin, chymotrypsin, elastase, cathepsin G, endoproteinase Lys-C, endoproteinase Glu-C, or subtilisin activity, suggesting that inhibition of known serine proteases is not the biochemical pathway for the PEDF neurotrophic activity. C1 NIDDKD,PROT EXPRESS LAB,OFF INTRAMURAL RES,OFF DIRECTOR,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,CTR MOLEC SCI,GALVESTON,TX 77555. GEORGETOWN UNIV,MED CTR,DEPT RADIAT MED,WASHINGTON,DC 20007. RP BECERRA, SP (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 308,BETHESDA,MD 20892, USA. NR 33 TC 86 Z9 90 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 NOV 5 PY 1993 VL 268 IS 31 BP 23148 EP 23156 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500032 PM 8226833 ER PT J AU BENHAMOU, M RYBA, NJP KIHARA, H NISHIKATA, H SIRAGANIAN, RP AF BENHAMOU, M RYBA, NJP KIHARA, H NISHIKATA, H SIRAGANIAN, RP TI PROTEIN-TYROSINE KINASE P72(SYK) IN HIGH-AFFINITY IGE RECEPTOR SIGNALING - IDENTIFICATION AS A COMPONENT OF PP72 AND ASSOCIATION WITH THE RECEPTOR GAMMA-CHAIN AFTER RECEPTOR AGGREGATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; WHEAT-GERM-AGGLUTININ; PHOSPHOLIPASE C-GAMMA-1; MAST-CELLS; ANTIGEN RECEPTOR; MEDIATED SIGNAL; ZETA-CHAIN; PHOSPHORYLATION; RBL-2H3; TRANSDUCTION AB Protein-tyrosine phosphorylation plays a critical role in the high-affinity IgE receptor (FcepsilonRI) signaling. Here we investigated the involvement of the tyrosine kinase p72syk in FcepsilonRI signaling in the rat mast cell line RBL-2H3. Specific antibodies were raised against peptides synthesized on the basis of the deduced peptide sequence of an essentially full-length rat syk cDNA. The expression of p72syk in RBL-2H3 cells was demonstrated with these antibodies. The aggregation of FcepsilonRI led to the tyrosine phosphorylation of p72syk that was detected after 15 s of stimulation, reached a plateau by 5 min, and was not induced by calcium influx or protein kinase C activation. Association of p72syk with the tyrosine phosphorylated FcepsilonRIgamma chain was detected only after receptor aggregation. We previously demonstrated that aggregation of the FcepsilonRI on mast cells results in the tyrosine phosphorylation of a 72-kDa protein (pp72) involved in IgE signaling. The depletion of p72syk from RBL-2H3 cell lysates resulted in only a slight decrease in the amount of pp72. These results demonstrate that pp72 is composed of several phosphoproteins and identify p72syk as one component of pp72. These data, together with recent observations in T cells, indicate that the interaction between p72syk-related tyrosine kinases and zeta-related proteins could play an important role in signal transduction. RP BENHAMOU, M (reprint author), NIDR,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 238 Z9 239 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1993 VL 268 IS 31 BP 23318 EP 23324 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500058 PM 7693687 ER PT J AU KIM, MK MCCLASKEY, JH BODENNER, DL WEINTRAUB, BD AF KIM, MK MCCLASKEY, JH BODENNER, DL WEINTRAUB, BD TI AN AP-1-LIKE FACTOR AND THE PITUITARY-SPECIFIC FACTOR PIT-1 ARE BOTH NECESSARY TO MEDIATE HORMONAL INDUCTION OF HUMAN THYROTROPIN BETA-GENE EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR PIT-1/GHF-1; TRANSDUCTION PATHWAYS CONVERGE; FOS-PROTEIN COMPLEXES; DNA-BINDING ACTIVITY; POU-SPECIFIC DOMAIN; ALPHA-SUBUNIT GENE; THYROID-HORMONE; C-JUN; PHORBOL-ESTER; CYCLIC-AMP AB The human thyrotropin beta (hTSHbeta) gene is inducible by various agents including thyrotropin-releasing hormone, phorbol esters, or the adenylyl cyclase activator forskolin. In this study, we have characterized the functional properties of the TGGGTCA motif at -1/+6 of the hTSHbeta gene that is similar to the consensus phorbol ester response element (TRE) or the consensus cyclic AMP response element (CRE). We suggest that both protein kinases C and A as well as TRH share common mediator which recognizes the TGGGTCA element in activating the hTSHbeta promoter. Following stimulation by phorbol esters, forskolin, or TRH, the TGGGTCA-specific factor acts together with the pituitary-specific transcription factor Pit-1 (or GHF-1) bound to upstream sequences at -128 to -61 to mediate the induction of the hTSHbeta promoter. The induction requires that both factors bind to their own binding sites, but Pit-1 neither increases the binding of the TGGGTCA-specific factor to its target sequences nor associates with this factor to form a heterodimer. The TGGGTCA-specific factor is present in three cell lines tested and is composed of protein(s) immunologically related to c-Jun and c-Fos but not to the CRE-binding protein, CREB. By using the hTSHbeta reporter plasmids in which the TGGGTCA element is converted to consensus TRE or CRE motifs, we found that, within the context of the hTSHbeta promoter, the TGGGTCA element is a more potent TRE or CRE than the consensus TRE or CRE sequences. Based upon the results of this study, we propose a model in which the TGGGTCA-specific AP-1-like factor functionally cooperates with the tissue-specific factor Pit-1 to activate the hTSHbeta gene. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BLDG 10,RM 8014,BETHESDA,MD 20892. NR 79 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1993 VL 268 IS 31 BP 23366 EP 23375 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500065 PM 8226861 ER PT J AU DRISCOLL, WJ MARTIN, BM CHEN, HC STROTT, CA AF DRISCOLL, WJ MARTIN, BM CHEN, HC STROTT, CA TI ISOLATION OF 2 DISTINCT 3-HYDROXYSTEROID SULFOTRANSFERASES FROM THE GUINEA-PIG ADRENAL - EVIDENCE FOR 3-ALPHA-HYDROXY VERSUS 3-BETA-HYDROXY STEREOSPECIFICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PREGNENOLONE-BINDING PROTEIN; ESTROGEN SULFOTRANSFERASE; POLYACRYLAMIDE GELS; RAT-LIVER; PURIFICATION; PHOSPHORYLATION; ANDROSTERONE AB Two physically distinct hydroxysteroid sulfotransferases (HSTs) that demonstrate substrate specificity with respect to the orientation of the ring A 3-hydroxyl group have been isolated from the guinea pig adrenal gland. Nondenaturing liquid-phase isoelectric focusing permitted the separation of the activities, and reverse phase high performance liquid chromatography was used to purify the two proteins to homogeneity. The 3beta-HST had an apparent molecular mass of 33 kDa and utilized pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone as substrates. The 3alpha-HST was slightly smaller at 32 kDa and utilized allopregnanolone and androsterone as substrates. The proteins were further distinguished by isoelectric point, immunoreactivity, and tryptic peptide mapping. Peptides isolated from both guinea pig HSTs demonstrated significant amino acid sequence homology (approximately 65% identity) to rat liver HST; however, available sequence data from the two proteins did not yield differences that might account for their stereospecific substrate selectivity. This paper represents the first definitive report demonstrating the existence of discrete HSTs that exhibit substrate specificity based on the stereochemistry of the 3-hydroxyl group. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,ADRENAL CELL BIOL SECT,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC STRUCT & PROT CHEM,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. NR 29 TC 28 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 NOV 5 PY 1993 VL 268 IS 31 BP 23496 EP 23503 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500083 PM 8226877 ER PT J AU RITTER, JK YEATMAN, MT KAISER, C GRIDELLI, B OWENS, IS AF RITTER, JK YEATMAN, MT KAISER, C GRIDELLI, B OWENS, IS TI A PHENYLALANINE CODON DELETION AT THE UGT1 GENE-COMPLEX LOCUS OF A CRIGLER-NAJJAR TYPE-I PATIENT GENERATES A PH-SENSITIVE BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COS-1 CELLS; CLONING; EXPRESSION; PHENOL; CDNA; RAT; IDENTIFICATION; SPECIFICITY; DEFICIENCY; SUBSTRATE AB The characterization (Ritter, J. K., Chen, F., Sheen, Y. Y., Tran, H. M., Kimura, S., Yeatman, M. T., and Owens, I. S. (1992) J. Biol. Chem. 267,3257-3261) of the single-copy UGT1 gene complex encoding both bilirubin and phenol UDP-glucuronosyltransferases (transferase) has been critical to the determination of genetic defects in Crigler-Najjar Type I patients. The complex (UGT1A-UGT1G) codes for at least two bilirubin, three bilirubin-like, and two phenol transferases. Seven different exons 1, each with an upstream promoter and each encoding the amino terminus of an isoform, are arrayed in series with four common exons (encoding seven identical carboxyl termini) in the 3'-region of the locus. Predictably, a critical mutation in a common exon inactivates the entire locus. A deleterious mutation in an exon 1, as we report here for the UGT1A gene in a Crigler-Najjar Type I patient, predictably affects the amino terminus of that single isoform. The code for the predominant bilirubin isozyme, the HUG-Br1 protein, is missing the phenylalanine codon at position 170 in exon 1 of UGT1A, abolishing a conserved diphenylalanine. We demonstrate that, at the pH (7.6) routinely used for bilirubin glucuronidation studies, both the HUG-Br1 protein and human liver microsomes have approximately one-third the activity seen at the major pH optimum of 6.4 and at low ionic strength. The altered isozyme with nearly normal activity at pH 7.6 is inactive at pH 6.4, a result consistent with the definition of a pH-sensitive mutant. The K(m) value for bilirubin using the wild-type protein is approximately 2.5 muM at both pH 6.4 and 7.6 and that for the mutant is 5.0 muM at pH 7.6. The structure of the wild-type enzyme compared to that of the mutant indicates that hydrophobic properties at the active center are critical for metabolizing the lipophile-like substrate. The low ion/pH requirements for bilirubin glucuronidation may signal the basis for the distribution of these isozymes to an organelle (endoplasmic reticulum) that can establish compatible conditions/compartments for each catalysis. C1 NICHHD,HUMAN GENET BRANCH,GENET DISORDERS DRUG METAB SECT,BLDG 10,RM 9S-242,BETHESDA,MD 20892. OSPED MAGGIORE MILANO,CTR LIVER TRANSPLANTAT & METAB ASSISTANCE ACUTE HEPAT COMA,I-20122 MILAN,ITALY. NR 25 TC 60 Z9 63 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1993 VL 268 IS 31 BP 23573 EP 23579 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500094 PM 8226884 ER PT J AU FLETCHER, MC SAMELSON, LE JUNE, CH AF FLETCHER, MC SAMELSON, LE JUNE, CH TI COMPLEX EFFECTS OF PHENYLARSINE OXIDE IN T-CELLS - INDUCTION OF TYROSINE PHOSPHORYLATION AND CALCIUM MOBILIZATION INDEPENDENT OF CD45 EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYL-INOSITOL PATHWAY; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; HIGH-AFFINITY; TUBULE CELLS; ACTIVATION; KINASE; STIMULATION; PHOSPHOTYROSINE AB The effects of phenylarsine oxide, a phosphotyrosine phosphatase inhibitor, on early signal transduction events in human T cells were studied. Simultaneous stimulation of T cells with anti-CD3 monoclonal antibody and phenylarsine oxide prevented increased tyrosine phosphorylation of phospholipase Cgamma1. In contrast, treatment of resting T cells with phenylarsine oxide alone resulted in increased tyrosine phosphorylation of a number of other intracellular substrates. Further, phenylarsine oxide was able to cause an immediate disruption of signal transduction in T cells after anti-CD3 stimulation, as measured by a return of intracellular calcium concentration and inositol 1,4,5-trisphosphate production to base-line levels. Surprisingly, in view of the inhibitory effects of phenylarsine oxide on T cell receptor signal transduction, treatment of T cells with phenylarsine oxide alone caused a dose-dependent increase in intracellular-free calcium concentration that was not accompanied with detectable increases in inositol 1,4,5-trisphosphate production. The phenylarsine oxide-induced increase in free calcium had distinct kinetics from antigen receptor-activated calcium mobilization and was derived from both intracellular sources and increased plasma membrane calcium permeability. This effect was independent of the CD45 transmembrane tyrosine phosphatase. Phenylarsine oxide thus has complex effects on signal transduction in T cells that suggests multiple intracellular targets, and these should be considered in the interpretation of experiments using this agent to study cellular kinase and phosphatase interactions. Finally, the effects of phenylarsine oxide on cellular calcium homeostasis may provide a mechanism of action for the therapeutic and/or toxic effects of arsenicals used for various forms of chemotherapy. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 46 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1993 VL 268 IS 31 BP 23697 EP 23703 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF515 UT WOS:A1993MF51500110 PM 7693695 ER PT J AU JANINI, GM CHAN, KC BARNES, JA MUSCHIK, GM ISSAQ, HJ AF JANINI, GM CHAN, KC BARNES, JA MUSCHIK, GM ISSAQ, HJ TI SEPARATION OF PYRIDINECARBOXYLIC ACID ISOMERS AND RELATED-COMPOUNDS BY CAPILLARY ZONE ELECTROPHORESIS - EFFECT OF CETYLTRIMETHYLAMMONIUM BROMIDE ON ELECTROOSMOTIC FLOW AND RESOLUTION SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; WATER-SOLUBLE VITAMINS; NICOTINIC-ACID; FLUORESCENCE DETECTION; FLUORIMETRIC METHOD; ISONICOTINIC-ACID; SERUM; URINE; METABOLITE; TRYPTOPHAN AB The effect of the addition of cetyltrimethylammonium bromide (CTAB) to the buffer system in capillary electrophoresis on electroosmotic flow (EOF) is examined. At a CTAB concentration of 2.5.10(-4) M, EOF is anodal (flow towards the positive detector column end). With bare silica columns, anodal EOF first increases with increasing pH, up to a maximum in the pH range 4-6 depending on CTAB concentration, then decreases as pH is further increased. Optimum resolution of pyridinecarboxylic acid isomers is obtained at pH 2.7 with a 10 mM phosphate buffer and 30 mM CTAB. Using the same buffer system, optimum resolution for hydroxy-substituted pyridinecarboxylic acid isomers is obtained at pH 7.5. The use of CTAB results in a dramatic improvement in peak shape. Preliminary results, using an excimer laser operated at 248 nm, show that the fluorescence intensity of isonicotinic acid is substantially enhanced with the addition of 0.3% hydrogen peroxide to the phosphate buffer system. RP JANINI, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,POB B,FREDERICK,MD 21702, USA. NR 30 TC 39 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 5 PY 1993 VL 653 IS 2 BP 321 EP 327 DI 10.1016/0021-9673(93)83190-4 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MW222 UT WOS:A1993MW22200017 PM 8269059 ER PT J AU HEEGAARD, NHH ROBEY, FA AF HEEGAARD, NHH ROBEY, FA TI A CAPILLARY ELECTROPHORESIS-BASED ASSAY FOR THE BINDING OF CA2+ AND PHOSPHORYLCHOLINE TO HUMAN C-REACTIVE PROTEIN SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE C-REACTIVE PROTEIN; BINDING ASSAY; PHOSPHORYLCHOLINE; CA2+ BINDING; AFFINITY CAPILLARY ELECTROPHORESIS ID ZONE ELECTROPHORESIS; AFFINITY ELECTROPHORESIS; CHROMATOGRAPHY; SPECIFICITY; COMPLEMENT; CONSTANTS; COMPLEXES; PEPTIDES AB Affinity capillary electrophoresis was performed to quantitate the binding of Ca2+ and phosphorylcholine to human C-reactive protein (CRP). The assay requires no modifications of any of the molecules involved, uses minuscule amounts of protein (8.5 x 10(-15) mol per analysis, i.e., less than 1 pmol for 15 triplicate data points), and the binding could be examined under conditions of physiological ionic strength and pH. The values for the dissociation constants obtained here (K-D = 59 mu M for Ca2+-CRP and 18 mu M for the phosphorylcholine-CRP interaction) were in close agreement with previous studies using gel filtration and equilibrium dialysis. As long as one of the reactants can be detected and recovered quantitatively in the capillary electrophoresis system, the method is generally useful to study interactions where complexed molecules display an electrophoretic mobility that is different from that of unbound molecules and where the rates of association and dissociation are sufficiently fast. C1 NATL INST DENTAL RES,CELLULAR DEV & ONCOL LAB,PEPTIDE & IMMUNOCHEM UNIT,BETHESDA,MD. NR 34 TC 41 Z9 41 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 5 PY 1993 VL 166 IS 1 BP 103 EP 110 DI 10.1016/0022-1759(93)90333-3 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA MH034 UT WOS:A1993MH03400011 PM 8228279 ER PT J AU GRANSTON, AE NASH, HA AF GRANSTON, AE NASH, HA TI CHARACTERIZATION OF A SET OF INTEGRATION HOST FACTOR MUTANTS DEFICIENT FOR DNA-BINDING SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CROSS-LINKING; DIMERIZATION ASSAY; PCR SITE-DIRECTED MUTAGENESIS; DNA-BINDING PROTEIN ID SITE-SPECIFIC RECOMBINATION; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; IHF PROTEIN; SENSITIVE MUTATIONS; BENDS DNA; GENE; PURIFICATION; PRODUCT; POLYACRYLAMIDE RP NIMH, MOLEC BIOL LAB, BLDG 36, ROOM 1B-08, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 53 TC 51 Z9 51 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 NOV 5 PY 1993 VL 234 IS 1 BP 45 EP 59 DI 10.1006/jmbi.1993.1562 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF514 UT WOS:A1993MF51400005 PM 8230206 ER PT J AU NASHED, NT RAO, TVS JERINA, DM AF NASHED, NT RAO, TVS JERINA, DM TI STERICALLY INDUCED METHOXYL MIGRATION ON ACID-CATALYZED DEHYDRATION OF K-REGION TRANS-DIHYDRODIOL MONOMETHYL ETHERS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ARENE OXIDES; REARRANGEMENTS; 5,6-OXIDE; ADDUCTS AB The regioisomers of the trans-dihydrodiol monomethyl ethers (DME) at the K-regions of 4- and 7-methyl- and 7,12-dimethylbenz[a] anthracene, which possess a ring methyl substituent peri to the methoxyl group, react with BF3.etherate to form a single phenol and two regioisomeric phenol methyl ethers, one of which arises by migration of the methoxyl group. In contrast, for DME of benz[a]-anthracene and its 1-, 4-, 7-, 11- and 12-methyl- and 7,12-dimethyl-substituted derivatives where there is no peri methyl group, methoxyl migration does not occur, and thus only the phenol methyl ether resulting from loss of water is formed. These results are consistent with a mechanism in which the initially formed carbocation with a pseudoaxial methoxyl group must undergo either conformational change to align the bond of the leaving proton with the empty p-orbital prior to proton loss or migration of the methoxyl group to the adjacent carbocation via a cyclic oxonium ion. In the absence of a ring substituent peri to the methoxyl group, conformational change is faster than formation of the cyclic oxonium ion, and therefore migration of the methoxyl group does not occur. A methyl substituent peri to the methoxyl group raises the activation energy barrier for conformational isomerization due to adverse steric interaction between the two groups. Consequently, formation of the cyclic oxonium ion becomes competitive with conformational change. The resulting oxonium ion opens to the regioisomeric carbocation resulting in rearrangement. Formation of the cyclic oxonium ion in these reactions is analogous to the rapid internal return of the hydroxy carbocation intermediate to protonated epoxide that is thought to occur in the reactions of peri-methyl-substituted K-region arene oxides. RP NASHED, NT (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 13 TC 15 Z9 15 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 5 PY 1993 VL 58 IS 23 BP 6344 EP 6348 DI 10.1021/jo00075a030 PG 5 WC Chemistry, Organic SC Chemistry GA MF516 UT WOS:A1993MF51600030 ER PT J AU HATHCOCK, KS LASZLO, G DICKLER, HB BRADSHAW, J LINSLEY, P HODES, RJ AF HATHCOCK, KS LASZLO, G DICKLER, HB BRADSHAW, J LINSLEY, P HODES, RJ TI IDENTIFICATION OF AN ALTERNATIVE CTLA-4 LIGAND COSTIMULATORY FOR T-CELL ACTIVATION SO SCIENCE LA English DT Article ID EXPRESSION; PROLIFERATION; ANTIGEN-B7; MOLECULE; INVIVO; B7 AB Stimulation of T cell proliferation generally requires two signals: The first signal is provided by the T cell receptor binding to antigen, and the second signal or costimulus is provided by a different receptor-ligand interaction. In mouse and human, the CD28-B7 interaction has been identified as a source of costimulatory signals. We have identified a cell surface molecule (GL1) that is distinct from B7 and abundantly expressed on activated B cells. On activated B cells GL1, rather than B7, is the predominant ligand for the T cell-activation molecule CTLA-4. GL1 provides a critical signal for T cell-dependent responses in vitro and in vivo. C1 NIA,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. RP HATHCOCK, KS (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 483 Z9 485 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 5 PY 1993 VL 262 IS 5135 BP 905 EP 907 DI 10.1126/science.7694361 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF438 UT WOS:A1993MF43800037 PM 7694361 ER PT J AU FREEMAN, GJ BORRIELLO, F HODES, RJ REISER, H HATHCOCK, KS LASZLO, G MCKNIGHT, AJ KIM, J DU, LN LOMBARD, DB GRAY, GS NADLER, LM SHARPE, AH AF FREEMAN, GJ BORRIELLO, F HODES, RJ REISER, H HATHCOCK, KS LASZLO, G MCKNIGHT, AJ KIM, J DU, LN LOMBARD, DB GRAY, GS NADLER, LM SHARPE, AH TI UNCOVERING OF FUNCTIONAL ALTERNATIVE CTLA-4 COUNTER-RECEPTOR IN B7-DEFICIENT MICE SO SCIENCE LA English DT Article ID T-CELL ACTIVATION; INVIVO; EXPRESSION; MOLECULE; ANTIGEN; CLONES AB B7 delivers a costimulatory signal through CD28, resulting in interleukin-2 secretion and T cell proliferation. Blockade of this pathway results in T cell anergy. The in vivo role of B7 was evaluated with B7-deficient mice. These mice had a 70 percent decrease in costimulation of the response to alloantigen. Despite lacking B7 expression, activated B cells from these mice bound CTLA-4 and GL1 monoclonal antibody, demonstrating that alternative CTLA-4 ligand or ligands exist. These receptors are functionally important because the residual allogenic mixed lymphocyte responses were blocked by CTLA4Ig. Characterization of these CTLA-4 ligands should lead to strategies for manipulating the immune response. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,IMMUNOL RES DIV,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 40216] NR 21 TC 378 Z9 379 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 5 PY 1993 VL 262 IS 5135 BP 907 EP 909 DI 10.1126/science.7694362 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF438 UT WOS:A1993MF43800038 PM 7694362 ER PT J AU POZSGAY, V AF POZSGAY, V TI A SYNTHESIS OF 2-(TRIMETHYLSILYL)ETHYL ALPHA-D-MANNOPYRANOSIDE SO TETRAHEDRON LETTERS LA English DT Article ID SHIGELLA-DYSENTERIAE TYPE-1; 2-TRIMETHYLSILYLETHYL GLYCOSIDES; CONVERSION; CHLORIDES AB The first high yield synthesis is reported of 2-(trimethylsilyl)ethyl alpha-D-mannopyranoside, using 2-O-benzoylated mannosyl donors, as precursors. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 5 PY 1993 VL 34 IS 45 BP 7175 EP 7178 DI 10.1016/S0040-4039(00)79280-X PG 4 WC Chemistry, Organic SC Chemistry GA MF216 UT WOS:A1993MF21600006 ER PT J AU DASILVA, AMT SUFFREDINI, AF DANNER, RL AF DASILVA, AMT SUFFREDINI, AF DANNER, RL TI SELF-ADMINISTRATION OF SALMONELLA ENDOTOXIN - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARDIOVASCULAR DYSFUNCTION; ESCHERICHIA-COLI; CANINE MODEL; SEPTIC SHOCK; MORTALITY C1 NIH,BETHESDA,MD 20892. RP DASILVA, AMT (reprint author), GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007, USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 4 PY 1993 VL 329 IS 19 BP 1427 EP 1427 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MD949 UT WOS:A1993MD94900022 ER PT J AU LI, RX GAGE, D LADISCH, S AF LI, RX GAGE, D LADISCH, S TI BIOSYNTHESIS AND SHEDDING OF MURINE LYMPHOMA GANGLIOSIDES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE GANGLIOSIDE; GANGLIOSIDE BIOSYNTHESIS; GANGLIOSIDE SHEDDING; CERAMIDE; MURINE LYMPHOMA CELL ID N-ACETYLNEURAMINIC ACID; GLYCOLYNEURAMINIC ACID; MASS-SPECTROMETRY; CELL-LINE; HYDROXYLATION; GLYCOSPHINGOLIPIDS; SERUM; GLYCOLIPIDS; SEPARATION; EXPRESSION AB Ganglioside biosynthesis and subsequent shedding are a potential mechanism contributing to tumor cell escape from the host immune response. As a first step in identifying active molecular species, structural characterization and quantification of the purified individual cellular and shed gangliosides of YAC-1 murine lymphoma cells were undertaken. These studies uncovered three striking changes in ganglioside metabolism in cells passaged in vivo, compared with cells cultured in vitro. (i) Marked inhibition of GalNAcG(M1b) synthesis: G(M1b) was present in an equal proportion to its biosynthetic product GalNAcG(M1b) in vitro, but was present in a 6-fold higher concentration in vivo. (ii) Marked inhibition of NeuGc synthesis: NeuGc, present in vitro in an up to 7-fold higher concentration than its biosynthetic precursor NeuAc, was decreased in relative concentration in vivo (1:1). (iii) Selectivity of shedding: ganglioside shedding in vitro was generalized with respect to both carbohydrate structure and ceramide structure (mainly d18:1-C24:1 and d18:1-C16:0), while in vivo, there was selective shedding of gangliosides containing NeuGc and the shorter chain fatty acid. The reduced synthesis of NeuGc and of GalNAcG(M1b) in vivo, and the selective shedding of more polar ganglioside species, also in vivo, show that the extracellular environment can markedly affect cellular ganglioside metabolism. C1 GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,SCH MED,CTR CANC & TRANSPLANTAT BIOL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT BIOCHEM MOLEC BIOL,WASHINGTON,DC 20010. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. MICHIGAN STATE UNIV,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20010. FU NCI NIH HHS [CA 42361]; NCRR NIH HHS [NCRR RR00480] NR 38 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD NOV 3 PY 1993 VL 1170 IS 3 BP 283 EP 290 DI 10.1016/0005-2760(93)90011-W PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MF890 UT WOS:A1993MF89000009 PM 8218347 ER PT J AU LINDBERG, DAB SIEGEL, ER AF LINDBERG, DAB SIEGEL, ER TI USING MEDLINE TO SOLVE CLINICAL PROBLEMS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP LINDBERG, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1993 VL 270 IS 17 BP 2053 EP 2054 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MD882 UT WOS:A1993MD88200019 ER PT J AU OSHAUGHNESSY, JA COWAN, KH AF OSHAUGHNESSY, JA COWAN, KH TI DOSE-INTENSIVE THERAPY FOR BREAST-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; ADJUVANT CHEMOTHERAPY; PROGENITOR CELLS; SOLID TUMORS; STAGE-II; PHASE-II; DOXORUBICIN; CYCLOPHOSPHAMIDE; CARBOPLATIN RP OSHAUGHNESSY, JA (reprint author), NCI,MED BRANCH,MED BREAST CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 42 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1993 VL 270 IS 17 BP 2089 EP 2092 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MD882 UT WOS:A1993MD88200030 PM 8411576 ER PT J AU LEVIN, L SIMON, R HRYNIUK, W AF LEVIN, L SIMON, R HRYNIUK, W TI IMPORTANCE OF MULTIAGENT CHEMOTHERAPY REGIMENS IN OVARIAN-CARCINOMA - DOSE INTENSITY ANALYSIS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROSPECTIVE RANDOMIZED TRIAL; ADRIAMYCIN PLUS CYCLOPHOSPHAMIDE; COMBINATION CHEMOTHERAPY; CIS-PLATINUM; STAGE-III; COMPARING CISPLATIN; SINGLE-AGENT; HEXA-CAF; CANCER; DOXORUBICIN AB Background: In the previous meta-analysis of dose intensity (dosage) of chemotherapy in advanced ovarian cancer, we analyzed data on cyclophosphamide, altretamine (hexamethylmelamine), doxorubicin, and cisplatin. Only cisplatin showed statistically significant association of complete and partial clinical response with dose intensity. Purpose: This analysis updates the previous results and further characterizes response to cisplatin alone or in multiagent regimens. Methods: We analyzed data from 18 regimens containing platinum (cisplatin or carboplatin) that were used in nine new randomized trials, in addition to data from the 60 groups of patients in our previous study in which responses were reported. Relative dose intensity was calculated as a fraction of the dosage of a drug in the standard regimen of cyclophosphamide, altretamine, doxorubicin, and platinum (CHAP). We performed single and multiple regression analyses to determine the relationship between disease outcome and relative dose intensity for cyclophosphamide, platinum, and doxorubicin alone or in combination. Results: The association between outcome and dose intensity for platinum alone or in multiagent regimens was statistically significant. This association was of borderline significance for cyclophosphamide alone but was not significant for this drug in multiagent regimens. There were insufficient data to test the relationship for doxorubicin as a single agent, but in multiagent regimens, the relationship was borderline (P = .05). Multiagent regimens containing platinum produced greater response rates than platinum alone for any fixed, planned relative dose intensity for platinum. Conclusions: Our results support other published findings that use of cyclophosphamide and doxorubicin increases the efficacy of single-agent platinum. Relative dose intensity values for cyclophosphamide used alone were larger than those used in multiagent regimens, which might explain why the relationship between relative dose intensity and outcome for cyclophosphamide was not significant for use in multiagent regimens. Similarly, none of the multiagent regimens incorporated doxorubicin at a relative dose intensity for which the drug is found to be effective as a single agent. Implications: Prospective clinical trials are required to test the effect of higher relative dose intensity for doxorubicin and cyclophosphamide added to platinum in advanced ovarian cancer. An important element in the design of prospective trials will be to test for the relative importance of dose intensity versus total dose. This testing is best achieved in a three-arm study design such as that reported in adjuvant treatment of stage II breast cancer conducted by the Cancer and Leukemia Group B. C1 UNIV WESTERN ONTARIO,FAC MED,DEPT ONCOL,LONDON N6A 3K7,ONTARIO,CANADA. NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,CTR CANC,SAN DIEGO,CA 92103. RP LEVIN, L (reprint author), LONDON REG CANC CTR,790 COMMISSIONERS RD E,LONDON N6A 4L6,ON,CANADA. NR 54 TC 82 Z9 82 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 NOV 3 PY 1993 VL 85 IS 21 BP 1732 EP 1742 DI 10.1093/jnci/85.21.1732 PG 11 WC Oncology SC Oncology GA ME916 UT WOS:A1993ME91600010 PM 8411257 ER PT J AU FREEDMAN, LS PRENTICE, RL CLIFFORD, C HARLAN, W HENDERSON, M ROSSOUW, J AF FREEDMAN, LS PRENTICE, RL CLIFFORD, C HARLAN, W HENDERSON, M ROSSOUW, J TI DIETARY-FAT AND BREAST-CANCER - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID TOTAL ENERGY-INTAKE; EPIDEMIOLOGIC ANALYSES C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,SEATTLE,WA 98104. NCI,DIV CANC PREVENT & CONTROL,DIET & CANC BRANCH,BETHESDA,MD 20892. NIH,OFF DIS PREVENT,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,CANC PREVENT RES PROGRAM,SEATTLE,WA 98104. NR 4 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 3 PY 1993 VL 85 IS 21 BP 1776 EP 1777 DI 10.1093/jnci/85.21.1776-a PG 2 WC Oncology SC Oncology GA ME916 UT WOS:A1993ME91600022 ER PT J AU BUTERS, JTM SCHILLER, CD CHOU, RC AF BUTERS, JTM SCHILLER, CD CHOU, RC TI A HIGHLY SENSITIVE TOOL FOR THE ASSAY OF CYTOCHROME-P450 ENZYME-ACTIVITY IN RAT, DOG AND MAN - DIRECT FLUORESCENCE MONITORING OF THE DEETHYLATION OF 7-ETHOXY-4-TRIFLUOROMETHYLCOUMARIN SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID LIVER-MICROSOMES; O-DEETHYLASE; METABOLISM; OXIDATION; DEMETHYLATION; PURIFICATION; HEPATOCYTES; INHIBITORS; P450IA2; P-450 AB The O-deethylation of 7-ethoxy-4-trifluoromethylcoumarin (EFC) by liver microsomes has been assessed as a method for monitoring the activity of cytochrome P450. The principle advantage of this substrate is the formation of a fluorescent product 7-hydroxy-4-trifluoromethylcoumarin (HFC) which can be assayed directly in the reaction medium. For rat microsomes the deethylated product was confirmed as the main metabolite, the reaction rate was linear with respect to both time and microsomal protein concentration and was independent of small changes in the added co-factors. A linear formation rate for the deethylated metabolite was also confirmed with dog and human microsomes. The intra-assay precision for rat, dog and human microsomes was 3, 5 and 4%, respectively. Hanes transformations of the dog and human data showed two phases, in contrast to a linear decline seen for the rat. Hybrid parameters for V(max) and K(m), calculated from the apparently linear portions of these curves. gave inter-day SD for the V(max) of rat, dog and man of 2, 14 and 4%, respectively, and approximately 15% for the K(m) in all species. The V(max) in rat, dog and human microsomes was 1.4 +/- 0.2, 4.3 +/- 1.5 and 0.9 +/- 0.5 nmol HFC/min/nmol P450, respectively. The K(m) was 11.0 +/- 3.1, 67 +/- 19 and 6.8 +/- 2.5 muM. respectively. Direct evidence that at least two isoenzymes (cytochrome P450 1A2 and 2E1) metabolize EFC was obtained by experiments with competitive, suicide and immuno-inhibitors. Compared with ethoxycoumarin, the involvement of P450 2E1 in O-deethylation seemed similar in the rat. In conclusion, EFC provides a straightforward and reproducible assay for microsomal enzyme activity, requiring at most 25 pmol/mL of cytochrome P450. C1 F HOFFMAN LA ROCHE AG,DIV PHARMA,PRECLIN RES,CH-4002 BASEL,SWITZERLAND. RP BUTERS, JTM (reprint author), NCI,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. RI Buters, Jeroen/G-5070-2011 NR 33 TC 106 Z9 106 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 2 PY 1993 VL 46 IS 9 BP 1577 EP 1584 DI 10.1016/0006-2952(93)90326-R PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MG312 UT WOS:A1993MG31200009 PM 8240414 ER PT J AU ADAMSON, PC BALIS, FM HAWKINS, ME MURPHY, RF POPLACK, DG AF ADAMSON, PC BALIS, FM HAWKINS, ME MURPHY, RF POPLACK, DG TI DESULFURATION OF 6-MERCAPTOPURINE - THE BASIS FOR THE PARADOXICAL CYTOTOXICITY OF THIOPURINES IN CULTURED HUMAN LEUKEMIC-CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HAMSTER OVARY CELLS; CYTO-TOXICITY; 6-THIOGUANINE; CHEMOSENSITIVITY; ASSAY; MERCAPTOPURINE; HYPOXANTHINE; DAMAGE AB The thiopurines have a wide array of effects on purine metabolism, but the primary mechanism of cytotoxicity for both 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) appears to be incorporation of drug into DNA following conversion to the thioguanylate form. In murine leukemic cell lines exposed to a range of thiopurine concentrations in vitro, cell survival curves have displayed a phenomenon termed paradoxical cytotoxicity, defined as a decrease in cytotoxicity with increasing drug concentration. The paradoxical cytotoxicity of thiopurines has usually been attributed to concentration-dependent perturbations in the cell cycle. The present study assessed whether the paradoxical cytotoxicity of 6-MP occurred in cultured human leukemic cells, and investigated the biochemical and cell-cycle alterations occurring in these lines at thiopurine concentrations associated with the reverse of cytotoxicity. Paradoxical cytotoxicity was observed in the two human leukemic cell lines examined, but only when 6-MP concentrations exceeded 100 muM. The extent of incorporation of 6-MP metabolites into DNA as thiol- versus non-thiol-containing metabolites was analyzed by performing parallel experiments with C-14- and S-35-radiolabeled drug. With 5 muM 6-MP, approximately 50% of drug was incorporated into DNA as a thionucleotide; however, with increasing drug concentrations, the degree of thionucleotide incorporation remained unchanged or decreased, and the amount incorporated as the desulfurated metabolite (presumably adenylate or guanylate) increased. With 500 muM 6-MP, less than 10% of the drug was incorporated as the thionucleotide. Perturbations in cell cycle reflected the relative amounts of thiol- and non-thiol-containing nucleotide formed at various concentrations of 6-MP. These results suggest that thiopurines may be vulnerable to a unique mechanism of detoxification, in which a human cell can metabolize a cytotoxic drug to a comparatively potent ''self-rescue'' agent. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,PHARMACOL & EXPTL THERAPEUT SECT,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 8 Z9 8 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 NOV 2 PY 1993 VL 46 IS 9 BP 1627 EP 1636 DI 10.1016/0006-2952(93)90333-R PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MG312 UT WOS:A1993MG31200016 PM 8240420 ER PT J AU THOMAS, DC NGUYEN, DC PIEGORSCH, WW KUNKEL, TA AF THOMAS, DC NGUYEN, DC PIEGORSCH, WW KUNKEL, TA TI RELATIVE PROBABILITY OF MUTAGENIC TRANSLESION SYNTHESIS ON THE LEADING AND LAGGING STRANDS DURING REPLICATION OF UV-IRRADIATED DNA IN A HUMAN CELL EXTRACT SO BIOCHEMISTRY LA English DT Note ID INDUCED MUTATIONS; MAMMALIAN-CELLS; REPAIR-PROFICIENT; INVITRO; SPECIFICITY; POLYMERASES; INITIATION; SPECTRA; ORIGIN; GENE AB We have previously demonstrated mutagenic bypass of pyrimidine dimers during SV40 origin-dependent replication of UV-irradiated DNA in human cell extracts [Thomas, D. C., & Kunkel, T. A. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7744-7748]. Here we use two vectors having the origin of replication on opposite sides of a lacZalpha reporter gene to examine the relative probability of mutagenic translesion synthesis on the leading and lagging strands. Although replication of both vectors is inhibited by UVB irradiation in a dose-dependent manner, the covalently closed DNA products of replication contain T4 endonuclease sensitive sites, indicating that bypass of cyclobutane pyrimidine dimers occurred. At fluences of 70 and 100 J/m2, the mutant frequencies obtained with both vectors are substantially higher than with control DNAs. Sequence analysis of mutants obtained with both vectors reveal three types of mutations at frequencies significantly above those obtained from replication of undamaged DNA. These are C --> T transitions, accounting for about two-thirds of the mutants, a small number of CC --> TT substitutions, and complex mutations. Comparing the distribution of C --> T substitutions in the two spectra permits an estimation of the probability of mutagenic translesion replication of the same sequence when replicated as the leading or lagging strand. The data suggest that the overall average UV-independent C --> T substitution probability per phenotypically detectable dipyrimidine site is the same during leading and lagging strand replication. However, statistically significant differences are observed when the distribution of C -> T substitutions is considered. The substitution probability at some positions is higher when replicated as the lagging strand than when replicated as the leading strand, while at other sites the opposite is observed. Thus the fidelity of leading and lagging strand translesion synthesis varies by position. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. NR 40 TC 31 Z9 31 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1993 VL 32 IS 43 BP 11476 EP 11482 DI 10.1021/bi00094a002 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ME656 UT WOS:A1993ME65600002 PM 8218213 ER PT J AU KROETZ, DL MCBRIDE, OW GONZALEZ, FJ AF KROETZ, DL MCBRIDE, OW GONZALEZ, FJ TI GLYCOSYLATION-DEPENDENT ACTIVITY OF BACULOVIRUS-EXPRESSED HUMAN LIVER CARBOXYLESTERASES - CDNA CLONING AND CHARACTERIZATION OF 2 HIGHLY SIMILAR ENZYME FORMS SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; MICROSOMAL BETA-GLUCURONIDASE; RAT-LIVER; ENDOPLASMIC-RETICULUM; UNTRANSLATED REGIONS; NUCLEOTIDE-SEQUENCE; MULTIGENE FAMILY; MESSENGER-RNAS; ESTERASE; PROTEINS AB A cDNA, designated hCE, encoding the entire sequence of a carboxylesterase, was isolated from a human liver lambdagt11 library. The hCE-deduced protein sequence contained 568 amino acids, including an 18 amino acid signal peptide sequence, and had a calculated molecular mass of the mature protein of 60 609 Da. A second cDNA, designated hCE(v), was isolated from the same lambdagt11 library and contained a 3-bp deletion resulting in the loss of the final amino acid in the signal peptide sequence (Ala-1) and a second 3-bp deltion leading to an in-frame loss of Gln345. Expression of mRNA corresponding to both hCE and hCE(v) was detected in eight adult human liver samples, with individual levels varying 5-fold (hCE) and 12-fold (hCE(v)). A single immunoreactive protein was detected in 13 adult human liver samples when probed with antibody directed against a rat carboxylesterase. Based on allele-specific oligonucleotide hybridizations, we believe that the hCE and hCE(v) cDNAs represent two distinct members of the carboxylesterase family. The carboxylesterase genes were localized to human chromosome 16 using a somatic cell hybrid mapping strategy. Baculovirus expression of hCE in Sf9 cells produced a protein with an estimated molecular mass of 59 000 Da. This enzyme was able to hydrolyze aromatic and aliphatic esters but possessed no catalytic activity toward amides or a fatty acyl CoA ester. Baculovirus-mediated expression of the hCE(v) cDNA yielded a second protein of 56 000 Da resulting from inefficient N-glycosylation of the hCE(v) protein. Although the substrate specificity for the hCE(v) protein was identical to that of expressed hCE for any given substrate, the specific activity for the hCE protein was always higher than that for the hCE(v) protein. Tunicamycin inhibition studies provided the first evidence that N-glycosylation of these luminal enzymes is essential for maximal catalytic activity. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP KROETZ, DL (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 69 TC 87 Z9 94 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1993 VL 32 IS 43 BP 11606 EP 11617 DI 10.1021/bi00094a018 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ME656 UT WOS:A1993ME65600018 PM 8218228 ER PT J AU MAY, M AARONSON, SA LAROCHELLE, WJ AF MAY, M AARONSON, SA LAROCHELLE, WJ TI PLATELET-DERIVED GROWTH FACTOR-AB HETERODIMER INTERCHAIN INTERACTIONS INFLUENCE SECRETION AS WELL AS RECEPTOR-BINDING AND ACTIVATION SO BIOCHEMISTRY LA English DT Article ID SIMIAN SARCOMA-VIRUS; TRANSFORMING GENE-PRODUCT; TYROSINE KINASE-ACTIVITY; PDGF-B-PROTEIN; SIGNAL TRANSDUCTION; BETA-RECEPTOR; HUMAN-ALPHA; CELL-LINES; V-SIS; IDENTIFICATION AB Platelet-derived growth factor (PDGF) is a disulfide-linked dimer comprised of two related polypeptide chains. To investigate the effects of an inactivating lesion introduced into one chain of the nascent PDGF dimer, approaches were developed to optimize synthesis, assembly, secretion, and purification of heterodimers between normal PDGF A and wild-type or mutant PDGF B. PDGF AB heterodimers were released into culture fluids less efficiently than PDGF AA, but to a greater degree than the cell-associated PDGF BB. These results suggest that interactions between two chains influence PDGF secretion. Analysis of heterodimers between PDGF A and disabled PDGF B mutants on cells that express either alpha or beta PDGFRs demonstrated that the impaired biologic activity of the mutant PDGF B chain was ameliorated with respect to binding and triggering of alpha PDGFRs. In cells that expressed both receptor types, heterodimers of mutant PDGF B and wild-type PDGF A gained substantially in their ability to recruit and trigger alpha, but not beta, PDGFRs. Partial rescue of impaired PDGF B mutant chain function by dimer formation with a wild-type PDGF A chain implies that interchain interactions markedly affect PDGFR binding and activation. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892. NR 39 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1993 VL 32 IS 43 BP 11734 EP 11740 DI 10.1021/bi00094a033 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ME656 UT WOS:A1993ME65600033 PM 8218243 ER PT J AU SAMUDZI, CT RUBIN, JR AF SAMUDZI, CT RUBIN, JR TI STRUCTURE OF RECOMBINANT BOVINE INTERFERON-GAMMA AT 3.0 ANGSTROM RESOLUTION SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID HUMAN IMMUNE INTERFERON; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; BETA; ANTIBODIES; EXPRESSION; RECEPTOR; DOMAINS; CELLS AB The three-dimensional crystal structure of recombinant bovine interferon-gamma was determined using the multiple isomorphous replacement method at 3.0 Angstrom and refined to an R factor of 19.2%. This protein crystallizes in space group P2(1)2(1)2(1) with unit-cell parameters of a=42.8, b=79.9 and c=85.4 Angstrom. There is one functional dimer in the asymmetric unit. The two polypeptide chains are related by a non-crystallographic twofold symmetry axis. The secondary structure is predominantly alpha-helical with extensive interdigitation of the alpha-helical segments of the polypeptide chains that make up the dimer. The secondary structure, tertiary structure and topology of this molecule are identical to the previously reported structures of recombinant rabbit interferon-gamma and recombinant human interferon-gamma. The molecular topology is also similar to that of murine interferon-beta. These structural similarities strongly indicate the presence of a unique topological feature (fold) among gamma-interferons from different species, and also among the different classes of interferons. RP SAMUDZI, CT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 31 TC 10 Z9 11 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1993 VL 49 BP 513 EP 521 DI 10.1107/S0907444993006924 PN 6 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA MF054 UT WOS:A1993MF05400002 PM 15299487 ER PT J AU RAYMOND, EG MILLS, JL AF RAYMOND, EG MILLS, JL TI PLACENTAL ABRUPTION - MATERNAL RISK-FACTORS AND ASSOCIATED FETAL CONDITIONS SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE PLACENTAL ABRUPTION; AGE; SMOKING; PARITY; CONGENITAL MALFORMATIONS; CONGENITAL HEART DEFECTS ID PREGNANCY; SMOKING AB Objective. To investigate maternal risk factors and fetal conditions associated with abruption. Methods. Prospective cohort study of 30,681 singleton pregnancies at least 28 weeks' gestation. Data collected by patient questionnaire at the first prenatal visit and by medical record review. Results. 307 women had abruption (1%). After adjustment, important maternal risk factors included age (in years; OR 1.03; 95% CL 1.00, 1.06; p=0.04) and less than 12 years of education (OR 1.58; 95% CL 1.10, 2.25; p=0.01). Each pack of cigarettes smoked per day increased the risk by approximately 40% (OR 1.39; 95% CL 1.09, 1.79; p=0.009). If abruption occurred, the perinatal mortality rate was substantially higher in women who smoked at least one pack per day than in nonsmokers (RR 2.53; 95% CL 1.14, 5.61; p=0.02). Abruption was also significantly associated with intrauterine growth retardation and fetal malformations. The increased malformation rate was due entirely to nearly a five-times increase in congenital heart defects (OR 4.63; 95% CL 2.49, 8.55; p=0.00000014). Conclusions: Heavier smoking increases the risk both of abruption and of perinatal death when abruption occurs. If the association between abruption and congenital heart defects is confirmed, early evaluation could lead to more prompt treatment of these malformations in infants delivered after abruption. RP RAYMOND, EG (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BLDG 6100,ROOM 7B03,BETHESDA,MD 20892, USA. NR 27 TC 79 Z9 80 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD NOV PY 1993 VL 72 IS 8 BP 633 EP 639 DI 10.3109/00016349309021156 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MM172 UT WOS:A1993MM17200009 PM 8259750 ER PT J AU DAWSON, DA ARCHER, LD AF DAWSON, DA ARCHER, LD TI RELATIVE FREQUENCY OF HEAVY DRINKING AND THE RISK OF ALCOHOL DEPENDENCE SO ADDICTION LA English DT Article ID DSM-III-R; INTOXICATION; CONSUMPTION; POPULATION AB Data from a national representative sample of US adults were analyzed to determine the association between the relative frequency of heavy drinking (the proportion of drinking occasions on which 5 + drinks were consumed) and past-year alcohol dependence, adjusting for the influences of average ethanol intake and sociodemographic factors. Fifty-seven percent of current drinkers reported never drinking 5 + drinks, and 21% drank 5 + drinks at least once but on less than 10% of all drinking occasions. Nine percent reported drinking 5 + drinks on at least half of all drinking occasions. Average daily intake was positively correlated with the relative frequency of heavy drinking, and both consumption measures were positively associated with the risk of alcohol dependence. Increases in either relative frequency of heavy drinking or average ethanol intake reduced, but did wt eliminate, the effect of the other on the risk of dependence. The excess risk of dependence associated with frequent heavy drinking varied among population subgroups and was increased by age, education, and female gender. RP DAWSON, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 24 TC 63 Z9 63 U1 0 U2 3 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 1993 VL 88 IS 11 BP 1509 EP 1518 DI 10.1111/j.1360-0443.1993.tb03136.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MF273 UT WOS:A1993MF27300006 PM 8286996 ER PT J AU ALLEN, JP FERTIG, JB TOWLE, LH BRYANT, K ALTSHULER, VB VRUBLEVSKY, AG VALENTIK, YV AF ALLEN, JP FERTIG, JB TOWLE, LH BRYANT, K ALTSHULER, VB VRUBLEVSKY, AG VALENTIK, YV TI STRUCTURE AND CORRELATES OF ALCOHOL DEPENDENCE IN CLINICAL-SAMPLES IN THE UNITED-STATES AND RUSSIA SO ADDICTION LA English DT Article ID DSM-III-R; VALIDITY; QUESTIONNAIRE; RELIABILITY; SEVERITY AB Using items from the Composite International Diagnostic Interview, dimensionality of the alcohol dependence syndrome was assessed in clinical samples in the United States and Russia. In both groups, a single-factor model provided a high degree of goodness of fit thus demonstrating cross-cultural coherence of the construct. The item dealing with narrowing of the drinking repertoire is most disparate in each sample. Severity of alcohol consequences was moderately related to alcohol dependence in both samples. Demographic variables, however, correlated less with seventy of consequences. After the effects of seventy of dependence and demographics were removed, quantity/frequency of recent alcohol consumption did not contribute to severity of consequences. Country, however, remained a significant, but small, predictor of severity of alcohol consequences. C1 STATE RES CTR ADDICT,MOSCOW,RUSSIA. RP ALLEN, JP (reprint author), NIAAA,DIV CLIN & PREVENT RES,ROOM 14C-20,ROCKVILLE,MD 20857, USA. NR 24 TC 2 Z9 2 U1 2 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 1993 VL 88 IS 11 BP 1535 EP 1543 DI 10.1111/j.1360-0443.1993.tb03139.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MF273 UT WOS:A1993MF27300009 PM 8286999 ER PT J AU CLERICI, M SISON, AV BERZOFSKY, JA RAKUSAN, TA BRANDT, CD ELLAURIE, M VILLA, M COLIE, C VENZON, DJ SEVER, JL SHEARER, GM AF CLERICI, M SISON, AV BERZOFSKY, JA RAKUSAN, TA BRANDT, CD ELLAURIE, M VILLA, M COLIE, C VENZON, DJ SEVER, JL SHEARER, GM TI CELLULAR IMMUNE FACTORS ASSOCIATED WITH MOTHER-TO-INFANT TRANSMISSION OF HIV SO AIDS LA English DT Article DE HIV; T-LYMPHOCYTES; MOTHER-TO-INFANT TRANSMISSION; SYNTHETIC PEPTIDES; INTERLEUKIN-2; POLYMERASE CHAIN REACTION; VIRAL CULTURES ID IMMUNODEFICIENCY-VIRUS ENVELOPE; POLYMERASE CHAIN-REACTION; INFECTED CHILDREN; RESPONSES; TYPE-1; LYMPHOCYTES; ANTIBODIES; EXPOSURE; PEPTIDE; MICE AB Objective: To study a possible correlate of protection in mother-to-infant transmission of HIV infection. In particular, to determine whether lack of HIV-specific T-helper (TH) function as indicated by HIV and non-HIV antigen-stimulated interleukin (IL)-2 production of mother and/or newborn peripheral blood leukocytes (PBL) is associated with mother-to-infant transmission of HIV. Methods: PBL from 21 HIV-seropositive pregnant women and 23 cord blood leukocytes (CBL) from their offspring were studied for in vitro TH function by IL-2 production in response to HIV and non-HIV antigens. Polymerase chain reaction (PCR) and viral culture assays were performed to determine HIV infection of the infants. Results: PBL from 10 out of 21 (48%) mothers and from eight out of 23 (35%) CBL samples responded to two or more out of five synthetic gp160 envelope (env) peptides. Three of the 23 (13%) offspring were shown to be HIV-infected by PCR and/or viral culture on follow-up. All three infected infants were from a subset whose CBL did not exhibit env-specific TH immunity. Conclusion: Our results demonstrate that fetal T cells can be primed to HIV env determinants in utero, suggest that HIV-specific TH immunity may be protective in newborns, and provide a possible means for identifying newborns who are at risk for HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC. NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. UNIV MILAN,CATTEDRA IMMUNOL,I-20122 MILAN,ITALY. CHILDRENS NATL MED CTR,WASHINGTON,DC. RI Venzon, David/B-3078-2008 NR 27 TC 111 Z9 114 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1993 VL 7 IS 11 BP 1427 EP 1433 DI 10.1097/00002030-199311000-00004 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MD962 UT WOS:A1993MD96200004 PM 8280407 ER PT J AU GRAZIOSI, C PANTALEO, G DEMAREST, JF COHEN, OJ VACCAREZZA, M BUTINI, L MONTRONI, M FAUCI, AS AF GRAZIOSI, C PANTALEO, G DEMAREST, JF COHEN, OJ VACCAREZZA, M BUTINI, L MONTRONI, M FAUCI, AS TI HIV-1 INFECTION IN THE LYMPHOID ORGANS SO AIDS LA English DT Article DE HIV; VIRAL BURDEN; PERIPHERAL BLOOD; LYMPHOID ORGANS; TISSUE DISTRIBUTION; HISTOPATHOLOGY; IMMUNE ACTIVATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR DENDRITIC CELLS; TYPE-1 INFECTION; NODES; LYMPHADENOPATHY; PATHOGENESIS; LYMPHOCYTES; MECHANISMS; RESERVOIRS; EXPRESSION AB Aim: To develop a model of HIV disease progression. Method: Comparative analysis of viral burden and replication between peripheral blood and lymphoid organs and of the changes in viral distribution in the lymphoid tissue. Results: In early-stage disease HIV-1-infected cells were sequestered in the lymphoid tissue, and the viral particles were concentrated and trapped in the germinal centers. The dichotomy in viral burden and viral replication between peripheral blood and lymphoid tissue was related to the histopathologic abnormalities associated with different stages of disease. Conclusions: These histopathologic abnormalities may not only explain the changes in viral distribution observed in the lymphoid tissue in different stages of the disease, but may also reflect different functional states of the immune system during the progression of HIV-1 infection from early- to late-stage disease. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV ANCONA,DEPT INTERNAL MED,ANCONA,ITALY. RI Pantaleo, Giuseppe/K-6163-2016 NR 26 TC 23 Z9 23 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1993 VL 7 SU 2 BP S53 EP S58 DI 10.1097/00002030-199311002-00012 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MU109 UT WOS:A1993MU10900012 PM 8161447 ER PT J AU KOJIMA, E SHIRASAKA, T ANDERSON, B CHOKEKIJCHAI, S SEI, S YARCHOAN, R MITSUYA, H AF KOJIMA, E SHIRASAKA, T ANDERSON, B CHOKEKIJCHAI, S SEI, S YARCHOAN, R MITSUYA, H TI MONITORING THE ACTIVITY OF ANTIVIRAL THERAPY FOR HIV-INFECTION USING A POLYMERASE CHAIN-REACTION METHOD COUPLED WITH REVERSE TRANSCRIPTION SO AIDS LA English DT Article DE HIV-1; VIRAL LOAD; POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION; DRUG RESISTANCE; POL GENE MUTATION ID SENSITIVITY; ZIDOVUDINE; BLOOD; DDI AB Aim: To monitor the anti-HIV-1 activity of antiretroviral agents in patients with HIV-1 infection. Method: Quantification of viral RNA copy in plasma or serum using a polymerase chain reaction method coupled with reverse transcription. Conclusions: The HIV-1 RNA copy number represents the HIV-1 viremia status in patients with HIV-1 infection. This copy number is likely to be useful in monitoring the effectiveness of antiviral therapy and the method is likely to be built into every clinical trial of anti-HIV-1 therapy in the near future. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,MED BRANCH,RETROVIRAL DIS SECT,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 16 TC 17 Z9 18 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1993 VL 7 SU 2 BP S101 EP S105 DI 10.1097/00002030-199311002-00019 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MU109 UT WOS:A1993MU10900019 PM 8161438 ER PT J AU LU, W SHIH, JWK TOURANI, JM EME, D ALTER, HJ ANDRIEU, JM AF LU, W SHIH, JWK TOURANI, JM EME, D ALTER, HJ ANDRIEU, JM TI LACK OF ISOLATE-SPECIFIC NEUTRALIZING ACTIVITY IS CORRELATED WITH AN INCREASED VIRAL BURDEN IN RAPIDLY PROGRESSING HIV-1-INFECTED PATIENTS SO AIDS LA English DT Article DE VIRAL QUANTITATION; SERUM VIREMIA; PERIPHERAL BLOOD MONONUCLEAR CELLS; AUTOLOGOUS ISOLATES; NEUTRALIZATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; PRIMARY HIV-1 INFECTION; TYPE-1 INFECTION; INDIVIDUALS; PLASMA; LYMPHOCYTES; VIREMIA; TROPISM; BLOOD AB Objective: To delineate the interaction between in vivo HIV replication and host antiviral immunity during disease progression in order to elucidate the pathogenesis of AIDS. Design: In a cohort of HIV-seropositive patients, the serum concentration of viral particles, the blood concentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlated with the rates of CD4+ T-cell depletion and disease progression. Methods: Using a quantitative reverse-transcriptase linked polymerase chain reaction assay, the concentration of viral particles was measured in blood samples from 103 initially symptom-free subjects who were followed up for greater than or equal to 24 months. The concentration of infectious virus and the neutralizing antibodies to autologous HIV isolates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. Results: Rapidly progressing patients (rate of decrease in CD4 cells greater than or equal to 60%) had a high concentration of viral particles and a high concentration of infectious virus associated with an undetectable serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells <30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specific neutralizing antibodies. Slowly progressing patients (rate of decrease in CD4 cells greater than or equal to 30 and <60%) showed an intermediate profile. Conclusions: Progression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T-lymphocyte population. C1 UNIV PARIS 05,LAENNEC HOSP,TUMOUR IMMUNOL LAB,F-75007 PARIS,FRANCE. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 39 TC 20 Z9 20 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1993 VL 7 SU 2 BP S91 EP S99 DI 10.1097/00002030-199311002-00018 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MU109 UT WOS:A1993MU10900018 PM 7909232 ER PT J AU VANGEMEN, B KIEVITS, T NARA, P HUISMAN, HG JURRIAANS, S GOUDSMIT, J LENS, P AF VANGEMEN, B KIEVITS, T NARA, P HUISMAN, HG JURRIAANS, S GOUDSMIT, J LENS, P TI QUALITATIVE AND QUANTITATIVE DETECTION OF HIV-1 RNA BY NUCLEIC-ACID SEQUENCE-BASED AMPLIFICATION SO AIDS LA English DT Article DE NUCLEIC ACID SEQUENCE-BASED AMPLIFICATION; HIV-1; RNA; AMPLIFICATION; QUANTIFICATION; MUTATION DETECTION ID PCR; INDIVIDUALS AB Aim: To develop a method to detect HIV-1 viral RNA by amplifying a specific nucleic acid sequence. Method: The nucleic acid sequence-based amplification (NASBA) method uses the simultaneous activity of avian myeloblastosis virus reverse transcriptase, T7 RNA polymerase and RNase H to amplify a specific nucleic acid target sequence. Validation: An in vitro cultured HIV-1 stock solution was used to validate the NASBA method and determine the variation in RNA measurement. Conclusion: Although NASBA is theoretically capable of specific amplification of RNA or DNA, it is most suitable for amplification of RNA, and therefore for detection of HIV-1 viral RNA. C1 BLOOD TRANSFUS SERV,CENT LAB,AMSTERDAM,NETHERLANDS. ACAD MED CENTRUM AMSTERDAM,AMSTERDAM,NETHERLANDS. NCI,TUMOR CELL BIOL LAB,VIRUS BIOL SECT,FREDERICK,MD. RP VANGEMEN, B (reprint author), ORGANON TEKN,BOSEIND 15,BOXTEL,NETHERLANDS. NR 11 TC 56 Z9 56 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1993 VL 7 SU 2 BP S107 EP S110 DI 10.1097/00002030-199311002-00020 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MU109 UT WOS:A1993MU10900020 PM 8161439 ER PT J AU BOLLINGER, RC QUINN, TC LIU, AY STANHOPE, PE HAMMOND, SA VIVEEN, R CLEMENTS, ML SILICIANO, RF AF BOLLINGER, RC QUINN, TC LIU, AY STANHOPE, PE HAMMOND, SA VIVEEN, R CLEMENTS, ML SILICIANO, RF TI CYTOKINES FROM VACCINE-INDUCED HIV-1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES - EFFECTS ON VIRAL REPLICATION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; FACTOR-ALPHA; CELL CLONE; INFECTED-CELLS; KAPPA-B; INVITRO REPLICATION; INTERFERON-GAMMA; GROWTH-FACTOR AB Cytolytic T lymphocytes (CTLs) specific for the human immunodeficiency virus (HIV-1) envelope glycoproteins have been cloned from HIV-1-seronegative human volunteers immunized with HIV-1 gp160-based candidate vaccines. Although vaccine-induced CTLs can potentially contribute to the antiviral response by direct lysis of infected cells, these CTLs may also produce cytokines that alter HIV-1 gene expression in other infected cells present in the microenvironment where CTL-target cell interactions occur. Vaccine-induced CTL clones were therefore examined for production of cytokines that affect HIV-1 gene expression in chronically infected T lymphocytic and promonocytic cell lines. Enhancement of HIV-1 gene expression was observed with supernatants from CD4(+) CTL clones and with supernatants from a subset of CD8(+) CTL clones. For each clone studied, upregulation of HIV-1 gene expression in chronically infected T cell lines resulted from the antigen-specific release by CTLs of tumor necrosis factor alpha (TNF-alpha). CD4(+) and CD8(+) CTLs that released TNF-alpha on antigen stimulation were also shown to express a biologically active 26-kDa transmembrane form of TNF-alpha, which was sufficient to induce upregulation of HIV-1 gene expression in chronically infected T cells placed in direct contact with the CTLs. Supernatants from antigen-activated, vaccine-induced CD4(+) and CD8(+) CTLs also caused upregulation of HIV-1 gene expression in chronically infected promonocytic cells. A subset of CD8(+) CTL clones also produced a soluble factor(s) that inhibited HIV-1 replication in acutely infected autologous CD4(+) blasts. Supernatants from CD4(+) CTLs had no effect on HIV-1 replication in acutely infected CD4(+) blasts. These results suggest that cytokine production as weal as cytolytic activity should be evaluated in the analysis of the potential antiviral effects of vaccine-induced CTLs. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,BALTIMORE,MD 21205. FU NIAID NIH HHS [AI28108, 5U01-AI27668-07, AI32871] NR 61 TC 24 Z9 25 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1993 VL 9 IS 11 BP 1067 EP 1077 DI 10.1089/aid.1993.9.1067 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MK130 UT WOS:A1993MK13000004 PM 7906131 ER PT J AU KITAMURA, K BESANSKY, NJ RUDOLPH, D NUTMAN, TB FOLKS, TM LAL, RB AF KITAMURA, K BESANSKY, NJ RUDOLPH, D NUTMAN, TB FOLKS, TM LAL, RB TI UNINTEGRATED 2-LONG TERMINAL REPEAT CIRCULAR HUMAN T-LYMPHOTROPIC VIRUS-DNA ACCUMULATION DURING CHRONIC HTLV INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; I INFECTION; VIRAL-DNA; MEMBERS; TISSUE; AIDS AB Accumulation of unintegrated human T lymphotropic virus (HTLV) DNA was analyzed in long-term T cell lines infected with HTLV type I (HTLV-I) or type II (HTLV-II). By using a polymerase chain reaction-based assay, amplified products of expected size were obtained in all of the HTLV-I-infected (n = 7) and HTLV-II-infected (n = 8) cell lines. The signal intensities of the hybridizing band varied greatly among the cell lines and did not correlate with HTLV p24(gag) antigen production. Further analysis of HTLV-I-infected clones demonstrated considerable variability in the unintegrated DNA accumulation, suggesting that either the epigenetic status of the host cell or some environmental factor determines the occurrence of unintegrated DNA. The presence of lower levels of unintegrated DNA in most of the HTLV-infected, long-term cell lines presumably results in persistent noncytopathic infection. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333. NIAID,PARASIT DIS LAB,BETHESDA,MD 20894. NR 22 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1993 VL 9 IS 11 BP 1167 EP 1172 DI 10.1089/aid.1993.9.1167 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MK130 UT WOS:A1993MK13000016 PM 8312058 ER PT J AU LEIBEL, RL DUFOUR, M HUBBARD, VS LANDS, WEM AF LEIBEL, RL DUFOUR, M HUBBARD, VS LANDS, WEM TI ALCOHOL AND CALORIES - A MATTER OF BALANCE SO ALCOHOL LA English DT Article DE ALCOHOL; METABOLIC ENERGY; BODY MASS INDEX; SATIATION; CALORIMETRY; THERMOREGULATION; FOOD CALORIES ID UNITED-STATES ADULTS; INDUCED POIKILOTHERMIA; ETHANOL SENSITIVITY; BODY-TEMPERATURE; BRAIN MEMBRANES; MICE; METABOLISM; INVIVO; WEIGHT; LIVER AB Many epidemiological studies show that alcohol-derived calories added to food intake of men and women in amounts of 0-25% of total energy do not appreciably alter the average daily intake of other macronutrients (carbohydrate, fat, and protein). With such lack of evidence for caloric compensation, alcohol and its calories seem to make little contribution to metabolic energy, body weight, or body composition (as indicated by the body mass index, BMI). In fact, a major study by Colditz et al. (Am. J. Clin. Nutr. 54:49-55; 1991) reported a clear inverse relationship between alcohol intake and BMI for women! Research on alcohol metabolism has left unresolved some apparent contradictions regarding the effect of alcohol on caloric control, appetite and satiation, and body mass and composition. To resolve those apparent contradictions, the National Institute on Alcohol Abuse and Alcoholism cosponsored with the National Institute of Diabetes and Digestive and Kidney Diseases and the Beltsville Human Nutrition Research Center of the U.S. Department of Agriculture an all-day workshop titled ''Alcohol and Calories: A Matter of Balance'' on January 27, 1993. The workshop included sessions on calorimetry and body mass maintenance, alcohol metabolism, thermoregulation, and an overview of energy balance. This report provides summaries of the four discussion sessions at the workshop. C1 NIAAA,DIV BASIC RES,ROCKVILLE,MD 20857. ROCKEFELLER UNIV,HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20857. NIDDK,NUTR SCI BRANCH,BETHESDA,MD 20892. NR 24 TC 17 Z9 17 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1993 VL 10 IS 6 BP 429 EP 434 DI 10.1016/0741-8329(93)90059-W PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA MP290 UT WOS:A1993MP29000002 ER PT J AU HUNT, WA AF HUNT, WA TI ARE BINGE DRINKERS MORE AT RISK OF DEVELOPING BRAIN-DAMAGE SO ALCOHOL LA English DT Article DE ETHANOL; BINGE DRINKING; REPEATED WITHDRAWAL; BRAIN DAMAGE; NMDA; CALCIUM; GLUCOCORTICOIDS ID INHIBIT GLUCOSE-TRANSPORT; ETHANOL WITHDRAWAL; ALCOHOL WITHDRAWAL; HIPPOCAMPAL DAMAGE; PHYSICAL-DEPENDENCE; GLUCOCORTICOID ENDANGERMENT; CHRONIC EXPOSURE; RAT HIPPOCAMPUS; KAINIC ACID; MICE AB Alcoholism is often associated with brain damage and cognitive deficits. Because drinking patterns can include periods of alcohol consumption followed by abstinence, binge drinking may enhance the possibility of brain damage. Chronic administration of ethanol leads to upregulation of N-methyl-D-aspartate (NMDA) and calcium receptors and increased release of glucocorticoids. NMDA-mediated mechanisms and glucocorticoid actions on the hippocampus are associated with brain damage. Thus, ethanol withdrawal may make the brain more vulnerable to damage from these mechanisms, especially with binge drinking. Therapeutic adjuncts for treating ethanol withdrawal, including NMDA, calcium, and glucocorticoid antagonists, may eventually prove useful in preventing further brain damage in alcoholism. RP HUNT, WA (reprint author), NIAAA,DIV BASIC RES,NEUROSCI & BEHAV RES BRANCH,5600 FISHERS LANE,RM 16C-05,ROCKVILLE,MD 20857, USA. NR 44 TC 78 Z9 79 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1993 VL 10 IS 6 BP 559 EP 561 DI 10.1016/0741-8329(93)90083-Z PG 3 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA MP290 UT WOS:A1993MP29000026 PM 8123218 ER PT J AU FLEISHER, TA BLAESE, RM AF FLEISHER, TA BLAESE, RM TI NEW APPROACHES IN THE THERAPY OF IMMUNODEFICIENCY SO ALLERGY PROCEEDINGS LA English DT Article RP FLEISHER, TA (reprint author), NCI,IMMUNOL SERV,CC & METAB BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD NOV-DEC PY 1993 VL 14 IS 6 BP 409 EP 411 DI 10.2500/108854193778792821 PG 3 WC Allergy SC Allergy GA MR585 UT WOS:A1993MR58500005 PM 8157164 ER PT J AU COHEN, SG AF COHEN, SG TI DISCOVERY AND REDISCOVERY SO ALLERGY PROCEEDINGS LA English DT Note RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD NOV-DEC PY 1993 VL 14 IS 6 BP 427 EP 428 DI 10.2500/108854193778792849 PG 2 WC Allergy SC Allergy GA MR585 UT WOS:A1993MR58500009 PM 8157166 ER PT J AU RICHARDSON, PE LANDRY, JE COHEN, SG AF RICHARDSON, PE LANDRY, JE COHEN, SG TI IMMUNOLOGISTS HONORED BY COMMEMORATIVE AND SPECIAL ISSUES OF POSTAGE STAMPS SO ALLERGY PROCEEDINGS LA English DT Note RP RICHARDSON, PE (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD NOV-DEC PY 1993 VL 14 IS 6 BP 429 EP 438 DI 10.2500/108854193778792786 PG 10 WC Allergy SC Allergy GA MR585 UT WOS:A1993MR58500010 PM 8157167 ER PT J AU HOEG, JM KLIMOV, AN AF HOEG, JM KLIMOV, AN TI CHOLESTEROL AND ATHEROSCLEROSIS - THE NEW IS THE OLD REDISCOVERED SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 ST PETERSBURG EXPTL MED INST,DEPT BIOCHEM,ST PETERSBURG,RUSSIA. RP HOEG, JM (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1993 VL 72 IS 14 BP 1071 EP 1072 DI 10.1016/0002-9149(93)90863-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MD559 UT WOS:A1993MD55900015 PM 8213588 ER PT J AU GUYER, MS COLLINS, FS AF GUYER, MS COLLINS, FS TI THE HUMAN GENOME PROJECT AND THE FUTURE OF MEDICINE SO AMERICAN JOURNAL OF DISEASES OF CHILDREN LA English DT Article ID DEPENDENT DIABETES-MELLITUS; POLYMERASE CHAIN-REACTION; GENETIC-LINKAGE MAP; MYOTONIC-DYSTROPHY; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; CLOSE LINKAGE; DNA-SEQUENCE; CTG REPEAT; FRAGILE-X AB The Human Genome Project is an international research effort the goal of which is to analyze the structure of human DNA and to determine the location of the estimated 100 000 human genes. Another component of the program is to analyze the DNA of a set of nonhuman model organisms to provide comparative information that is essential for understanding how the human genome functions. The project began formally in 1990. In this report, we summarize the rapid progress that has already been made; the impact that the resources already developed by the Human Genome Project have had on the ability of investigators to identify and isolate human genes, particularly those associated with disease; and the promise that the project offers for profoundly altering our approach to medical care, from one of treatment of advanced disease to prevention based on the identification of individual risk. RP GUYER, MS (reprint author), NIH,NATL CTR HUMAN GENOME RES,ROOM 605,BLDG 38A,BETHESDA,MD 20892, USA. NR 81 TC 27 Z9 28 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0002-922X J9 AM J DIS CHILD JI Am. J. Dis. Child. PD NOV PY 1993 VL 147 IS 11 BP 1145 EP 1152 PG 8 WC Pediatrics SC Pediatrics GA MF838 UT WOS:A1993MF83800002 PM 8237907 ER PT J AU DIBISCEGLIE, AM FONG, TL FRIED, MW SWAIN, MG BAKER, B KORENMAN, J BERGASA, NV WAGGONER, JG PARK, Y HOOFNAGLE, JH AF DIBISCEGLIE, AM FONG, TL FRIED, MW SWAIN, MG BAKER, B KORENMAN, J BERGASA, NV WAGGONER, JG PARK, Y HOOFNAGLE, JH TI A RANDOMIZED, CONTROLLED TRIAL OF RECOMBINANT ALPHA-INTERFERON THERAPY FOR CHRONIC HEPATITIS-B SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; VIRUS-INFECTION; ALPHA-2-INTERFERON; HBSAG; ALFA AB Objectives: To evaluate the effect of recombinant alpha-interferon in chronic hepatitis B. Methods: Patients were stratified at entry according to their serum aspartate aminotransferase (AST) values, randomized to receive a-interferon (alfa-2b, 10 million units three times weekly) or to be untreated controls for 16 wk. Effect of therapy on levels of hepatitis B viral (HBV) DNA and aminotransferase activities in serum and hepatitis B e antigen (HBeAg) status was monitored. Results: Forty-seven patients entered the trial; 11 of 25 (44%) patients receiving interferon responded by clearing HBeAg and HBV DNA within 6 months, compared to one of 22 (5%) controls (p < 0.05). Among those with serum AST values < 100 U/L, 33% responded and among those with AST values > 100 U/L, 60% responded. Within the 6-month study period, 36% of treated patients had normal serum alanine aminotransferase (ALT) values, and 16% had cleared hepatitis B surface antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg. Interferon was stopped early in three patients (6.5%), and dosage was reduced in a further 16 patients (35%) because of adverse effects. Predictive factors for a response were the pretreatment serum ALT and AST activities. Conclusions: Alpha-Interferon therapy (three times weekly) is relatively well tolerated and is effective in clearing HBeAg and HBV DNA in approximately one-third of treated patients. RP DIBISCEGLIE, AM (reprint author), NIDDKS,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,ROOM 9C 103B,BETHESDA,MD 20892, USA. NR 17 TC 66 Z9 67 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 1993 VL 88 IS 11 BP 1887 EP 1892 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MF797 UT WOS:A1993MF79700016 PM 8237937 ER PT J AU DELEO, JM PUCINO, F CALIS, KA CRAWFORD, KW DORWORTH, T GALLELLI, JF AF DELEO, JM PUCINO, F CALIS, KA CRAWFORD, KW DORWORTH, T GALLELLI, JF TI PATIENT-INTERACTIVE COMPUTER-SYSTEM FOR OBTAINING MEDICATION HISTORIES SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE COMPUTERS; PATIENT INFORMATION; RECORDS; REPORTS ID INTERVIEW PERFORMANCE; DRINKING HISTORY; PERCEPTIONS; INTERNS; DOCTORS; DRUGS AB A portable, patient-interactive computerized system for obtaining medication histories is described. A comprehensive interview script modeling pharmacist-conducted medication-history interviews was written in lay language. The script contains sections on demographics, current medical conditions, medication regimen, medication compliance, symptoms, allergy history, dietary history, psychosocial history, and occupational and environmental exposure; it also asks the patient to evaluate the system. Some of the information requested is often not obtained by physicians during the history and physical examination. A program that conducts the interview by processing a computerized version of the script was developed with Microsoft QuickBASIC. The program was designed to be run on a personal computer microprocessor so that an interview can be conducted virtually anywhere by using a desktop or laptop computer. Summary reports suitable for inclusion in the medical record are generated after each interview. Patients using the system took an average of 40 minutes to complete an interview. They entered data easily and accurately, and they gave the system a high overall rating. The medication-history interviewing system described produces useful, comprehensive, and consistent reports and requires about the same amount of time to conduct an interview as a human interviewer. C1 NIH,DEPT PHARM,DIV COMP RES & TECHNOL,BLDG 10,ROOM IN-257,900 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,DEPT PHARM,DRUG INFORMAT SERV,BETHESDA,MD 20892. NIH,DEPT PHARM,OUTPATIENT PHARM SERV SECT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. NR 32 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD NOV PY 1993 VL 50 IS 11 BP 2348 EP 2352 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MF849 UT WOS:A1993MF84900024 PM 8266960 ER PT J AU NYLANDER, LA DEMENT, JM AF NYLANDER, LA DEMENT, JM TI CARCINOGENIC EFFECTS OF WOOD DUST - REVIEW AND DISCUSSION SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Review DE WOOD DUST; OCCUPATIONAL EXPOSURE; FURNITURE WORKERS; CARPENTERS; NASAL CANCER; OCCUPATIONAL DISEASE; TOXICITY; MUTAGENICITY; PREVENTION ID PARA-NASAL SINUSES; OCCUPATIONAL RISK-FACTORS; DEATH CERTIFICATE ANALYSIS; SQUAMOUS-CELL CANCERS; HIGH-WYCOMBE AREA; FURNITURE WORKERS; HODGKINS-DISEASE; LUNG-CANCER; SINONASAL CANCER; HISTOLOGICAL-CHANGES AB Occupational exposure to wood dust (alone or chemically treated) is associated with an increased risk of developing adenocarcinoma of the nasal cavity. The specific causative agents, i.e., wood dust alone (natural products), wood dust with additives used in the processing or manufacturing of wood products, and/or physical determinants of wood dust and the associated risk factors, are not known or understood. The strongest association of exposure to wood dust and development of nasal cancer is observed in those occupations where workers are exposed to hard wood dust and chemical additives are not used. The time between first occupational exposure to wood dust and the development of adenocarcinoma of the nasal cavity averages 40 years (range 7-70 years). The epidemiological data available are not sufficient to make a definitive assessment between wood dust exposure and increased fisk for cancer other than nasal cancer. The toxicity, mutagenicity, and carcinogenicity of wood dust to laboratory animals or in vitro with animal or microbial cells have not been thoroughly studied. Thus there is no direct experimental evidence on the potential hazards of wood dust. Data are insufficient or lacking on 1) wood dust exposure levels in ambient air and worker's breathing zone, and the deposition in the nasal cavity; 2) hard vs. soft wood dusts; 3) particle size and shape; 4) chemical composition of wood dust and the extent of contamination with chemical additives; and 5) interaction between inhaled wood dust, chronic irritation, and tobacco smoking. These data are required so that one can understand the association between wood dust exposure and nasal cavity tumors, along with demographic differences in cancer rates, and to develop strategies for intervention and reduction of disease causing agents in order to reduce risk to wood industry workers. (C) 1993 Wiley-Liss, Inc. C1 NIEHS,OFF OCCUPAT HLTH & TECH SERV,RES TRIANGLE PK,NC 27709. RP NYLANDER, LA (reprint author), NATL INST OCCUPAT HLTH,DIV IND HYG,S-17184 SOLNA,SWEDEN. NR 175 TC 78 Z9 79 U1 4 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1993 VL 24 IS 5 BP 619 EP 647 DI 10.1002/ajim.4700240511 PG 29 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MD084 UT WOS:A1993MD08400010 PM 8266936 ER PT J AU LEROITH, D WERNER, H PHILLIP, M ROBERTS, CT AF LEROITH, D WERNER, H PHILLIP, M ROBERTS, CT TI THE ROLE OF INSULIN-LIKE GROWTH-FACTORS IN DIABETIC KIDNEY-DISEASE SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE DIABETIC; RENAL; INSULIN-LIKE GROWTH FACTORS; RENAL PLASMA FLOW ID GLOMERULAR-FILTRATION RATE; RENAL PLASMA-FLOW; I MESSENGER-RNA; IGF-I; GENE-EXPRESSION; HYPERTROPHY; SEVERITY; MELLITUS RP LEROITH, D (reprint author), NIDDKD,MOLEC & CELLULAR PHYSIOL SECT,DIABET BRANCH,BLDG 10,ROOM 8S239,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 NR 27 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1993 VL 22 IS 5 BP 722 EP 726 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA MF844 UT WOS:A1993MF84400015 PM 8238020 ER PT J AU POWELL, CM CHANDRA, RS SAAL, HM AF POWELL, CM CHANDRA, RS SAAL, HM TI PHAVER SYNDROME - AN AUTOSOMAL RECESSIVE SYNDROME OF LIMB PTERYGIA, CONGENITAL HEART ANOMALIES, VERTEBRAL DEFECTS, EAR ANOMALIES, AND RADIAL DEFECTS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE NEW SYNDROME; AUTOSOMAL RECESSIVE; VATER ASSOCIATION; VERTEBRAL DEFECTS; LIMB PTERYGIA; MENINGOMYELOCELE; RADIAL DEFECTS ID JARCHO-LEVIN SYNDROME; VACTERL-ASSOCIATION; DYSPLASIA; SIBLINGS AB We have studied 2 sibs with vertebral, radial, congenital heart, and ear defects. The second patient also had limb pterygia and meningomyelocele. The abnormalities in these two sibs are seen in the VATER association; however, distinguishing these cases from the VATER association are the findings of pterygia, meningomyelocele, and probable autosomal recessive inheritance. We propose the acronym PHAVER syndrome for limb pterygia, heart defects, autosomal recessive inheritance, vertebral defects, ear anomalies and radial defects. This represents a new autosomal recessive disorder with phenotypic variability. (C) 1993 Wiley-Liss, Inc. C1 NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,SCH MED,DEPT MED GENET,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,SCH MED,DEPT PATHOL,WASHINGTON,DC 20052. NR 18 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 1993 VL 47 IS 6 BP 807 EP 811 DI 10.1002/ajmg.1320470602 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MD992 UT WOS:A1993MD99200001 PM 8279476 ER PT J AU HEIBA, IM DEMEESTER, CA XIA, YR DIEP, A GEORGE, VT AMOS, CI SRINIVASAN, SR BERENSON, GS ELSTON, RC LUSIS, AJ AF HEIBA, IM DEMEESTER, CA XIA, YR DIEP, A GEORGE, VT AMOS, CI SRINIVASAN, SR BERENSON, GS ELSTON, RC LUSIS, AJ TI GENETIC CONTRIBUTIONS TO QUANTITATIVE LIPOPROTEIN TRAITS ASSOCIATED WITH CORONARY-ARTERY DISEASE - ANALYSIS OF A LARGE PEDIGREE FROM THE BOGALUSA HEART-STUDY SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CANDIDATE GENES; SIB-PAIR LINKAGE; ASSOCIATION; CHOLESTEROL; TRIGLYCERIDE ID APOLIPOPROTEIN-B-GENE; LOW-DENSITY-LIPOPROTEIN; TRANSFER PROTEIN CETP; FRAGMENT LENGTH POLYMORPHISMS; SERUM-CHOLESTEROL LEVELS; HUMAN HEPATIC LIPASE; DNA POLYMORPHISMS; MYOCARDIAL-INFARCTION; BIRACIAL COMMUNITY; LINKAGE ANALYSIS AB A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein Al level times this ratio (apoAI x LDL-C/HDL-C). APOB (Pvull) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein Al locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease. (C) 1993 Wiley-Liss, Inc. C1 LSU,MED CTR,DEPT BIOMETRY & GENET,1901 PERDIDO ST,NEW ORLEANS,LA 70112. LSU,MED CTR,CTR HUMAN & MOLEC GENET,NEW ORLEANS,LA. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,DEPT MICROBIOL & MOLEC GENET,DEPT MED,LOS ANGELES,CA 90024. NIAMSD,GENET STUDIES SECT,BETHESDA,MD. TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT APPL HLTH SCI,NEW ORLEANS,LA 70118. FU NHLBI NIH HHS [HL 07567, HL 48361, HL 28481] NR 72 TC 25 Z9 25 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 1993 VL 47 IS 6 BP 875 EP 883 DI 10.1002/ajmg.1320470615 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA MD992 UT WOS:A1993MD99200014 PM 8279486 ER PT J AU MELNICK, SL SHAHAR, E FOLSOM, AR GRAYSTON, JT SORLIE, PD WANG, SP SZKLO, M AF MELNICK, SL SHAHAR, E FOLSOM, AR GRAYSTON, JT SORLIE, PD WANG, SP SZKLO, M TI PAST INFECTION BY CHLAMYDIA-PNEUMONIAE STRAIN TWAR AND ASYMPTOMATIC CAROTID ATHEROSCLEROSIS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR RISK-FACTORS; CYTOMEGALO-VIRUS; ARTERY DISEASE; ASSOCIATION; PATHOGENESIS; CHOLESTEROL; ULTRASOUND; ANTIBODY; CELLS AB PURPOSE: To determine whether past infection by Chlamydia pneumoniae strain TWAR is associated with asymptomatic atherosclerosis. Previous studies have linked this organism with symptomatic coronary heart disease. SUBJECTS AND METHODS: Between 1986 and 1989, 15,800 men and women aged 45 to 64 years were examined as part of the Atherosclerosis Risk in Communities Study, a prospective cohort study of atherosclerosis being conducted in 4 United States communities. The examination included B-mode ultrasonography of the carotid arteries and an assessment of cardiovascular disease risk factors. Carotid wall thickening (blood-intima to medial-adventitial interface) in the absence of clinical cardiovascular disease was considered evidence of asymptomatic atherosclerosis. In 1991, IgG antibody titers to TWAR were assayed by microimmunofluorescence in stored sera from 326 case-control pairs matched by age group, race, sex, examination period, and field center. A titer of -1:8 or higher was considered a positive TWAR antibody response. RESULTS: Seventy-three percent of atherosclerosis cases had serologic evidence of past TWAR infection versus 63% of controls (matched odds ratio 1.76; 95% confidence interval, 121 to 2.57). After adjustment for age, hypertension, diabetes, cigarette smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and education, the odds ratio for atherosclerosis was essentially unchanged at 2.00 (95% confidence interval, 1.19 to 3.35). The association was stronger for individuals aged 45 to 54 years than for those aged 55 to 64 years. CONCLUSION: There was a significant cross-sectional association between past TWAR infection and asymptomatic atherosclerosis. This organism may be a contributor to the pathogenesis of atherosclerosis. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454. JOHNS HOPKINS SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT PATHOBIOL,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55019, N01-HC-55015] NR 39 TC 197 Z9 198 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1993 VL 95 IS 5 BP 499 EP 504 DI 10.1016/0002-9343(93)90332-J PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MG686 UT WOS:A1993MG68600008 PM 8238066 ER PT J AU BIZZI, A RIGHINI, A TURNER, R LEBIHAN, D DESPRES, D DICHIRO, G ALGER, JR AF BIZZI, A RIGHINI, A TURNER, R LEBIHAN, D DESPRES, D DICHIRO, G ALGER, JR TI MR OF DIFFUSION SLOWING IN GLOBAL CEREBRAL-ISCHEMIA SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE BRAIN, ISCHEMIA; BRAIN, MAGNETIC RESONANCE; MAGNETIC RESONANCE, DIFFUSION-WEIGHTED SCANNING; MAGNETIC RESONANCE, EXPERIMENTAL; ANIMAL STUDIES ID NUCLEAR-MAGNETIC-RESONANCE; BLOOD-FLOW; CAT BRAIN; ENERGY-METABOLISM; RAT-BRAIN; PROLONGED ISCHEMIA; T2-WEIGHTED MRI; P-31 NMR; SPECTROSCOPY; RECOVERY AB PURPOSE: To investigate the causal connections between ischemia and the hyperintensity in diffusion-weighted MR images that has been associated with it. METHODS: Diffusion-weighted and T2-weighted MR imaging were used in a feline global cerebral ischemia/reperfusion model. Single 30-minute vascular occlusions followed by reperfusion were studied. Global occlusions were used to avoid interpretive complications associated with the temporally unstable hemodynamics of the penumbral zones around focal occlusions and the possible growth of the ischemic and penumbral regions with time. RESULTS: Diffusion-weighted hyperintensity and the associated diffusional slowing were not attributable exclusively to the cessation of blood flow because: 1) it does not appear abruptly at the onset of ischemia; 2) it resolves slowly early in reperfusion; and 3) it reappears after prolonged reperfusion. CONCLUSION: The times during which diffusion-weighted hyperintensity is manifested during ischemia, and recovers with reperfusion, point to a role for energy metabolism failure. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Turner, Robert/C-1820-2008; Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 NR 48 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1993 VL 14 IS 6 BP 1347 EP 1354 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA MG537 UT WOS:A1993MG53700018 PM 8279330 ER PT J AU TOKUNAGA, M LAND, CE UEMURA, Y TOKUDOME, T TANAKA, S SATO, E AF TOKUNAGA, M LAND, CE UEMURA, Y TOKUDOME, T TANAKA, S SATO, E TI EPSTEIN-BARR-VIRUS IN GASTRIC-CARCINOMA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID LYMPHOEPITHELIOMA-LIKE CARCINOMA; POLYMERASE CHAIN-REACTION; LYMPHOID STROMA; ADENOCARCINOMA; STOMACH; DNA AB Epstein-Barr virus (EBV) is known to be related to lymphoid tumors and some types of epithelial tumors, including lymphoepithelioma-like gastric carcinoma with marked lymphocytic stroma. In this study, prevalence of EBV involvement in gastric cancer, and characteristics of tumors with such involvement, were investigated by EBV-encoded RNA 1 in situ hybridization applied to paraffin sections, including the tumor and adjacent gastric tissue, from 999 gastric carcinomas observed in 9 70 consecutive cases from a large Japanese hospital. EBV involvement occurred in 69 percent of lesions, a significantly lower proportion than has been observed in a North American series. Involvement was significantly more frequent among males, in tumors in the upper part of the stomach, and in adenocarcinomas of the moderately differentiated tubular and poorly differentiated solid or medullary types. Almost all carcinomas with marked lymphoid stroma were EBV-positive. Positive lesions were characterized by the presence of uniform hybridized signals in almost all carcinoma cells and by their absence from adjacent non-neoplastic tissue. C1 NCI,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD. KAGOSHIMA CITY MED ASSOC HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. KAGOSHIMA UNIV,FAC MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. RP TOKUNAGA, M (reprint author), KAGOSHIMA CITY HOSP,DEPT PATHOL,KAJIYA CHO 20-17,KAGOSHIMA 892,JAPAN. NR 24 TC 222 Z9 228 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1993 VL 143 IS 5 BP 1250 EP 1254 PG 5 WC Pathology SC Pathology GA MF656 UT WOS:A1993MF65600002 PM 8238241 ER PT J AU DEHAYE, JP VALDEZ, IH TURNER, RJ AF DEHAYE, JP VALDEZ, IH TURNER, RJ TI BETA-ADRENERGIC STIMULATION AND CAMP MOBILIZE CA2+ FROM AN IP3-INSENSITIVE POOL IN RAT SUBMANDIBULAR GRANULAR DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ISOPROTERENOL; FORSKOLIN; INOSITOL PHOSPHATES; EXOCRINE SECRETION; STIMULUS-SECRETION COUPLING ID INOSITOL TRISPHOSPHATE PRODUCTION; CYCLIC-AMP; INTRACELLULAR CALCIUM; 2ND MESSENGERS; CA-2+; CELLS; HEPATOCYTES; HORMONE; RELEASE; ACINI AB The beta-adrenergic agonist isoproterenol induced an increase in intracellular calcium concentration ([Ca2+]i) in rat submandibular granular ducts that was blocked by beta-adrenergic but not by a-adrenergic or muscarinic antagonists. This effect was only partially inhibited by the selective beta1- and beta2-adrenergic antagonists atenolol and ICI-118,551, but was completely blocked by the combination of the two, suggesting the involvement of multiple (or atypical) beta-adrenergic receptor subtypes. The response to isoproterenol was mimicked by forskolin, 3-isobutyl-1-methylxanthine, and dibutyryl adenosine 3',5'-cyclic monophosphate, but it was not blocked by protein kinase inhibitors. The response of [Ca2+]i to isoproterenol was sustained in Ca2+-replete medium but transient in Ca2+-free medium, indicating the involvement of both Ca2+ entry and release from intracellular stores. However, isoproterenol stimulation produced no increase in ductal inositol phosphate levels. In addition, isoproterenol was still able to increase [Ca2+]i after the carbachol-induced depletion of inositol 1,4,5-trisphosphate (IP3)-sensitive calcium stores. We conclude that isoproterenol, acting through cAMP, releases Ca2+ from an IP3-insensitive intracellular store in salivary granular ducts. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. FREE UNIV BRUSSELS,INST PHARM,DEPT GEN BIOCHEM,B-1070 BRUSSELS,BELGIUM. NR 33 TC 35 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1993 VL 265 IS 5 BP C1356 EP C1362 PN 1 PG 7 WC Physiology SC Physiology GA MJ167 UT WOS:A1993MJ16700021 ER PT J AU MORAN, A TURNER, RJ AF MORAN, A TURNER, RJ TI SECRETAGOGUE-INDUCED RVD IN HSY CELLS IS DUE TO K+ CHANNELS ACTIVATED BY CA2+ AND PROTEIN-KINASE-C SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SALIVARY DUCTS; SALT REABSORPTION; VOLUME REGULATION; REGULATORY VOLUME DECREASE ID TRANSPORT; LINE; SECRETION AB To maintain cell volume, absorptive epithelia must coordinate ion fluxes associated with transcellular transport with those required for volume regulation. K+ channels are thought to play a central regulatory role in this process. Electronic cell sizing was used to study the regulatory volume decrease (RVD) response of the human salivary ductal cell line HSY. Following a hypotonic challenge, RVD was markedly enhanced by the muscarinic agonist carbachol (half-maximal effect approximately 1.4 muM). Carbachol-induced RVD was mimicked by the K+ ionophore valinomycin and inhibited by K+ channel blockers, indicating that it is due to the activation of K+ channels. Carbachol-induced RVD was blocked by maneuvers that blunted the carbachol-induced rise in intracellular Ca2+ concentration ([Ca2+]i) and mimicked by ionomycin-induced increases in [Ca2+]i, but concentrations of ionomycin (100 nM) yielding [Ca2+]i well above carbachol-induced levels were required. However, when treatment with 2.5 nM ionomycin, which produced [Ca2+]i in the carbachol-generated range, was combined with treatment with low concentrations of an active phorbol ester, an enhancement of RVD similar to that observed with carbachol alone was observed. These data provide strong evidence that carbachol-induced RVD in the HSY cells involves K+ channels that are tightly regulated by both [Ca2+]i and protein kinase C. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1A06,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT PHYSIOL,IL-84105 BEER SHEVA,ISRAEL. RI MORAN, ARIE/F-1210-2012 NR 23 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1993 VL 265 IS 5 BP C1405 EP C1411 PN 1 PG 7 WC Physiology SC Physiology GA MJ167 UT WOS:A1993MJ16700027 ER PT J AU MEBAZAA, A MAYOUX, E MAEDA, K MARTIN, LD LAKATTA, EG ROBOTHAM, JL SHAH, AM AF MEBAZAA, A MAYOUX, E MAEDA, K MARTIN, LD LAKATTA, EG ROBOTHAM, JL SHAH, AM TI PARACRINE EFFECTS OF ENDOCARDIAL ENDOTHELIAL-CELLS ON MYOCYTE CONTRACTION MEDIATED VIA ENDOTHELIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Note DE ENDOCARDIAL ENDOTHELIUM; ENDOTHELIUM; MYOCARDIAL CONTRACTION; VENTRICLE ID CARDIAC MYOCYTES; MUSCLE; PERFORMANCE; RABBIT AB Endocardial endothelium is reported to modulate myocardial contraction by releasing diffusible factors, but the nature of the agent(s) responsible is unknown. In the present study we investigated the potential role of endothelin in these effects. Cultured sheep endocardial endothelial cells were found to express endothelin-1 mRNA and to release endothelin-1 into superfusing solution. This superfusate induced positive inotropic effects in isolated rat cardiac myocytes, associated with an increase in the cytosolic Ca2+ transient. Similar positive inotropic effects were induced by vascular endothelial cell superfusate as well as by synthesized endothelin-1, administered at concentrations similar to those present in the superfusate. Incubation of endocardial endothelial cell superfusate with endothelin-1-specific antiserum reduced the free endothelin-1 concentration to undetectable levels and abolished both the positive inotropic effect and the rise in cytosolic Ca2+. These findings indicate that endocardial endothelial cells may modulate myocardial contraction in part through the release of endothelin-1 and suggest that endocardial as well as vascular endothelium could exert potent paracrine effects on myocardium. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,PULM ANESTHESIOL LAB,BALTIMORE,MD 21205. UNIV WALES COLL MED,DEPT CARDIOL,CARDIFF CF4 4XN,S GLAM,WALES. RP MEBAZAA, A (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,MEYER 295,600 N WOLFE ST,BALTIMORE,MD 21224, USA. NR 26 TC 114 Z9 114 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1993 VL 265 IS 5 BP H1841 EP H1846 PN 2 PG 6 WC Physiology SC Physiology GA MJ168 UT WOS:A1993MJ16800048 ER PT J AU EVERSON, CA AF EVERSON, CA TI SUSTAINED SLEEP-DEPRIVATION IMPAIRS HOST-DEFENSE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE INFECTIOUS DISEASE; FEVER; METABOLISM; BACTEREMIA; SEPTICEMIA; IMMUNE SYSTEM ID FATAL FAMILIAL INSOMNIA; RAT; LYMPHOCYTE; CACHECTIN; SERUM; SHOCK AB Prolonged sleep deprivation in rats causes an unexplained hypercatabolic state, secondary malnutrition symptoms, and mortality. The nature of the vital impairment has long been a mystery. Its determination would help to elucidate the type of organic dysfunction that sleep prevents. There are no gross detectable disturbances in intermediary metabolism, clinical chemistry, or hematological indexes that provide substantial clues to the mediation of sleep-deprivation effects. Furthermore, postmortem examinations reveal no systematic morphological or histopathological findings. Taken together, the cachexia and the absence of evidence of structural damage or organ dysfunction pointed to involvement of a regulatory system that was diffuse, possibly the immune system. Blood cultures revealed invasion by opportunistic microbes to which there was no febrile response. These results suggest that the life-threatening condition of prolonged sleep deprivation is a breakdown of host defense against indigenous and pathogenic microorganisms. RP EVERSON, CA (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH, BLDG 10, ROOM 45 239, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 36 TC 157 Z9 161 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1993 VL 265 IS 5 BP R1148 EP R1154 PN 2 PG 7 WC Physiology SC Physiology GA MJ168 UT WOS:A1993MJ16800074 PM 8238617 ER PT J AU REGIER, DA AF REGIER, DA TI THE LINKAGE OF HEALTH-CARE REFORM AND HEALTH-SERVICES RESEARCH SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material RP REGIER, DA (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1993 VL 150 IS 11 BP 1613 EP 1615 PG 3 WC Psychiatry SC Psychiatry GA MF102 UT WOS:A1993MF10200001 PM 8214168 ER PT J AU MORGAN, MJ CASCELLA, NG STAPLETON, JM PHILLIPS, RL YUNG, BCK WONG, DF SHAYA, EK LONDON, ED AF MORGAN, MJ CASCELLA, NG STAPLETON, JM PHILLIPS, RL YUNG, BCK WONG, DF SHAYA, EK LONDON, ED TI SENSITIVITY TO SUBJECTIVE EFFECTS OF COCAINE IN DRUG-ABUSERS - RELATIONSHIP TO CEREBRAL VENTRICLE SIZE SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; BETA-HYDROXYLASE ACTIVITY; SCHIZOPHRENIC-PATIENTS; MONOAMINE METABOLITES; SUBSTANCE-ABUSE; BRAIN ATROPHY; BASAL GANGLIA; SPINAL-FLUID; ABNORMALITIES; ENLARGEMENT AB Objective: The Purpose of this study was to assess the functional significance of ventricle-brain ratio (VBR) in terms of bow it might affect sensitivity to cocaine, an indirect dopamine agonist. Method: Relationships between VBR and subjective responses to acute intravenous cocaine hydrochloride were examined in 20 male polydrug abusers. Tests were performed in conjunction with positron emission tomography scans to measure cerebral glucose metabolism. Results: Subjective measures of effects of cocaine, including self-report ratings of intensity of the drug effect, scores on the morphine-benzedrine scale of the Addiction Research Center Inventory, and several items on visual analogue scales, correlated negatively with VBR. VBR also differed significantly among subjects who were grouped according to scores on items (''rush'' and ''crash'') of the Cocaine-Sensitive Scale (larger VBR in subjects with weaker responses). VBR was not correlated with cocaine-induced changes in cerebral metabolic rates for glucose. Conclusions: Relative insensitivity to the subjective effects of cocaine in polydrug abusers with ventricle enlargement suggests that ventriculomegaly may reflect changes in periventricular brain regions that mediate these effects of cocaine. C1 NIDA,ADDICT RES CTR,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. NR 47 TC 11 Z9 11 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1993 VL 150 IS 11 BP 1712 EP 1717 PG 6 WC Psychiatry SC Psychiatry GA MF102 UT WOS:A1993MF10200017 PM 8214181 ER PT J AU FILLENBAUM, GG HANLON, JT CORDER, EH ZIQUBUPAGE, T WALL, WE BROCK, D AF FILLENBAUM, GG HANLON, JT CORDER, EH ZIQUBUPAGE, T WALL, WE BROCK, D TI PRESCRIPTION AND NONPRESCRIPTION DRUG-USE AMONG BLACK-AND-WHITE COMMUNITY-RESIDING ELDERLY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MEDICINE USE; PATTERNS; HEALTH; AGE AB Objectives. To examine and compare concomitants of prescription and nonprescription drug use of Black and White community-dwelling elderly. Methods. Information on prescription and nonprescription drug use, demographic and health characteristics, and use of health services was obtained from a probability-based sample of Black (n = 2152) and White (n = 1821) community-resident elderly in the Piedmont area of North Carolina. Descriptive statistics were calculated. Linear regression, in which sample weights and design effects were taken into account, was used for the final models. Results. For prescription drug use, 37% and 32% of the variance was explained for Whites and Blacks, respectively (6% and 5% for nonprescription drugs). Health status and use of medical services were the strongest predictors of prescription drug use for both races (with Medi-gap insurance also important for Whites and Medicaid important for Blacks). Demographic characteristics and self-assessed health were significant factors in the use of nonprescription drugs. Race independently predicted use of both types of drugs but explained only a small proportion of the variance. Conclusions. Health status and use of health services are importantly related to prescription drug use. Nonprescription drug use is difficult to explain. C1 DUKE UNIV,MED CTR,DIV GERIATR MED,DURHAM,NC 27710. UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC 27514. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP FILLENBAUM, GG (reprint author), DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,BOX 3003,DURHAM,NC 27710, USA. FU NIA NIH HHS [N01-AG-4-2110] NR 31 TC 77 Z9 77 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1993 VL 83 IS 11 BP 1577 EP 1582 DI 10.2105/AJPH.83.11.1577 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MF808 UT WOS:A1993MF80800015 PM 8238682 ER PT J AU OHKUBO, K BARANIUK, JN HOHMAN, RJ KAULBACH, HC HAUSFELD, JN MERIDA, M KALINER, MA AF OHKUBO, K BARANIUK, JN HOHMAN, RJ KAULBACH, HC HAUSFELD, JN MERIDA, M KALINER, MA TI HUMAN NASAL MUCOSAL NEUTRAL ENDOPEPTIDASE (NEP) - LOCATION, QUANTITATION, AND SECRETION SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID DIPEPTIDYL-CARBOXYPEPTIDASE ENKEPHALINASE; AWAKE GUINEA-PIGS; SUBSTANCE-P; 24.11 ENKEPHALINASE; NEUROGENIC INFLAMMATION; CONVERTING ENZYME; PATHO-PHYSIOLOGY; LEUKEMIA ANTIGEN; FERRET TRACHEA; AIRWAY HYPERRESPONSIVENESS AB Neutral endopeptidase (E.C.3.4.24.11, enkephalinase, NEP) is a potentially important enzyme capable of regulating the activity of neuropeptides released in the respiratory mucosa. In order to confirm the existence of NEP in the human respiratory mucosa, inferior nasal turbinate mucosae obtained at surgery and nasal secretions induced by topical provocations with methacholine, histamine, and allergen were analyzed for: (1) NEP activity (pmol product/min/ml) by enzymatic degradation of [H-3]leu-enkephalin, (2) the presence of NEP-immunoreactive material by Western blot analysis, and (3) cellular localization of NEP distribution by immunohistochemistry. NEP activity in human nasal secretions obtained after normal saline challenge was 0.15 +/- 0.06 pmol/min/ml. Secretion increased to 0.86 +/- 0.26 pmol/min/ml after methacholine provocation and 1.69 +/- 0.74 pmol/min/ml after histamine provocation. The increase in NEP activity in methacholine-induced secretions was prevented by atropine (0.13 +/- 0.06 pmol/min/nil). After methacholine, histamine, and antigen nasal provocation, the kinetics of NEP appearance correlated more closely to the glandular marker, lactoferrin, than with the vascular markers albumin and IgG. In homogenates of nasal mucosa, the membrane fraction contained significantly more NEP on a per mg protein basis than did the soluble fraction (227.6 +/- 50.52 versus 9.61 +/- 3.18 pmol/min/mg protein, respectively, P < 0.01, n = 6). NEP in the membrane fraction was detected as a single band migrating at 97 kD on Western blots using antibodies specific for NEP and the common acute lymphoblastic leukemia antigen (CALLA). Immunoreactive NEP was localized to serous cells of the submucosal glands, epithelial cells, and endothelial and myoepithelial cells of small vessels. Staining for NEP in the serous cells was of the same intensity as that in epithelial cells. These results indicate that 97 kD NEP-immunoreactive material exists in discrete locations in the nasal mucosa, including the epithelium, serous cells of the submucosal glands, and vessel walls, and that NEP activity is detected as a minor component in nasal secretions enriched by glandular products. In addition to the modulating functions of NEP on neuropeptide-mediated activities on vessels and glands, it is possible that NEP in secretions plays a role in regulating mucosal responses to luminal neuropeptides or other as yet uncharacterized NEP substrates. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV RHEUMATOL IMMUNOL & ALLERGY,3800 RESERVOIR RD NW,WASHINGTON,DC 20007. WASHINGTON HOSP CTR,DEPT FACIAL PLAST & RECONSTRUCT SURG,WASHINGTON,DC 20010. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT OTOLARYNGOL & PEDIAT,WASHINGTON,DC 20007. NR 60 TC 16 Z9 18 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1993 VL 9 IS 5 BP 557 EP 567 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA MF942 UT WOS:A1993MF94200014 PM 8217197 ER PT J AU HUBBERT, TE VUCICH, JJ ARMSTRONG, MR AF HUBBERT, TE VUCICH, JJ ARMSTRONG, MR TI LIGHTWEIGHT APRONS FOR PROTECTION AGAINST SCATTERED RADIATION DURING FLUOROSCOPY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 NIH,HENRY M JACKSON FDN,DEPT RADIOL,WARREN G MAGNUSON CLIN CTR,BLDG 10,BETHESDA,MD 20892. NR 6 TC 10 Z9 10 U1 2 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1993 VL 161 IS 5 BP 1079 EP 1081 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MD368 UT WOS:A1993MD36800038 PM 8273614 ER PT J AU ARBER, DA WEISS, LM JAFFE, ES AF ARBER, DA WEISS, LM JAFFE, ES TI NASAL LYMPHOMAS IN PERU - REPLY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID MALIGNANT-LYMPHOMAS; SINUSES C1 CITY HOPE NATL MED CTR,DIV PATHOL,DUARTE,CA 91010. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RP ARBER, DA (reprint author), SCOTT & WHITE MEM HOSP & CLIN,DEPT PATHOL,TEMPLE,TX 76508, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1993 VL 17 IS 11 BP 1195 EP 1195 DI 10.1097/00000478-199311000-00018 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA ME250 UT WOS:A1993ME25000018 ER PT J AU GAZZINELLI, RT GALVAO, LM KRAUTZ, G LIMA, APCA CANCADO, JR SCHARFSTEIN, J KRETTLI, AU AF GAZZINELLI, RT GALVAO, LM KRAUTZ, G LIMA, APCA CANCADO, JR SCHARFSTEIN, J KRETTLI, AU TI USE OF TRYPANOSOMA-CRUZI PURIFIED GLYCOPROTEIN (GP57/51) OR TRYPOMASTIGOTE-SHED ANTIGENS TO ASSESS CURE FOR HUMAN CHAGAS-DISEASE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ALPHA-GALACTOSYL ANTIBODIES; COMPLEMENT-MEDIATED LYSIS; LYTIC ANTIBODIES; RESISTANCE; SERA; SUSCEPTIBILITY; IDENTIFICATION; LAMININ AB With the exception of assays for the detection of antibodies promoting complement-mediated lysis of Trypanosoma cruzi, serologic tests have generally failed to assess the effectiveness of chemotherapy for Chagas' disease. Conventional serology, although useful for the diagnosis of infection, is not capable of determining which patients have been cured. Here we demonstrate that a high proportion of antibodies detected by conventional serology (using fixed epimastigotes or trypomastigotes or crude extracts obtained therefrom) are directed against the carbohydrate residue galactosylalpha1 - > 3 galactose (Gal alpha1 - > 3 Gal), a determinant also recognized by antibodies from noninfected healthy volunteers. In a study of 14 cured patients with long-term followup, we found that the persistently positive reactions detected using conventional serology were largely eliminated following immunoadsorption with melibiose. Because of their wide distribution among microorganisms of intestinal and pulmonary microflora, these carbohydrate determinants may keep stimulating lymphocytes previously primed by T. cruzi Galalpha1 - > 3 Gal epitopes, thereby accounting for false-positive results in cured patients. Consistent with this proposition, enzyme-linked immunosorbent assays performed with two distinct T. cruzi antigen preparations that lack the Galalpha1 - > 3 Gal epitope, namely purified GP57/51 and trypomastigote-shed antigens, were indeed capable of determining a cure after chemotherapy, albeit to a different degree. Collectively, the data indicate that conventional immunoassays prepared with highly specific T. cruzi antigens can be useful in the assessment of a cure after chemotherapy. C1 CTR PESQUISAS RENE RACHOU FIOCRUZ,BELO HORIZONT,BRAZIL. UNIV FED RIO JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,BR-21944 RIO JANEIRO,BRAZIL. UNIV FED MINAS GERAIS,ESCOLA MED,ICB,DEPT PARASITOL,BR-30000 BELO HORIZONT,MG,BRAZIL. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lima, Ana Paula/G-4122-2012 NR 33 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1993 VL 49 IS 5 BP 625 EP 635 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA MK141 UT WOS:A1993MK14100013 PM 8250103 ER PT J AU FITZGERALD, PC HARTLEY, RW AF FITZGERALD, PC HARTLEY, RW TI POLYETHENOADENOSINE PHOSPHATE AS A FLUOROGENIC SUBSTRATE FOR BARNASE SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID EXTRACELLULAR RIBONUCLEASE; PROTEIN STABILITY; BARSTAR; BINDING; EXPRESSION; MUTATION; FAMILY; RNA C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 20 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1993 VL 214 IS 2 BP 544 EP 547 DI 10.1006/abio.1993.1536 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ME957 UT WOS:A1993ME95700027 PM 8109747 ER PT J AU BERGER, SL MANROW, RE LEE, HY AF BERGER, SL MANROW, RE LEE, HY TI PHOENIX MUTAGENESIS - ONE-STEP REASSEMBLY OF MULTIPLY CLEAVED PLASMIDS WITH MIXTURES OF MUTANT AND WILD-TYPE FRAGMENTS SO ANALYTICAL BIOCHEMISTRY LA English DT Article RP BERGER, SL (reprint author), NCI,BIOCHEM LAB,GENES & GENE PROD SECT,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1993 VL 214 IS 2 BP 571 EP 579 DI 10.1006/abio.1993.1540 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ME957 UT WOS:A1993ME95700031 PM 7906495 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 MULTIPLE EFFECTS OF MORPHINE ON FACIAL SCRATCHING IN MONKEYS SO ANESTHESIA AND ANALGESIA LA English DT Article ID MEDULLARY DORSAL HORN; PERCEIVED INTENSITY; EPIDURAL MORPHINE; NOXIOUS HEAT; OPIOIDS; LABOR AB The medullary dorsal horn (MDH), the medullary homolog of the spinal dorsal horn, is a site where opioid-receptor agonists can act at opioid receptors to produce pronounced facial scratching, the behavioral correlate of pruritus. In the present study, after a 10-min baseline period, morphine (5.0 mug) was microinjected into the MDH of monkeys. Behavior was videotaped and facial scratches were counted by two independent raters. Morphine greatly increased facial scratching behavior, which is consistent with previous findings where mu-opioid receptor agonists microinjected into the MDH have been to induce dose-dependent, naloxone-reversible facial scratching in monkeys. In the current research, intramuscular (IM) administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), reversed this MDH morphine-induced scratching. Additionally, IM morphine (1.0 mg/kg) produced a substantial reduction in facial scratching behavior. Scratching behavior continued at a high rate after injection of saline (0.1 mL/kg, IM). These findings support the hypothesis that morphine has both pruragenic and antipruragenic activity, depending on the site of action. RP THOMAS, DA (reprint author), NIDR,NATL CARIES PROGRAM,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,BETHESDA,MD 20892, USA. NR 18 TC 24 Z9 24 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 NOV PY 1993 VL 77 IS 5 BP 933 EP 935 PG 3 WC Anesthesiology SC Anesthesiology GA ME496 UT WOS:A1993ME49600010 PM 8214729 ER PT J AU BOOCK, RJ DOAN, D GOLDSTEIN, D THIBAULT, LE AF BOOCK, RJ DOAN, D GOLDSTEIN, D THIBAULT, LE TI MODEL FOR SHORT-TERM INTRACRANIAL-PRESSURE CHANGES FOLLOWING TRAUMATIC INJURY SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article ID DIFFUSE AXONAL INJURY; HEAD-INJURY; ISCHEMIA; BRAIN; HYPOXIA; PRIMATE AB Results from primate studies show a transient increase in intracranial pressure (ICP) after a nonimpact inertial loading condition. The measured ICP increase varies linearly with the peak tangential load of these experiments. These experiments point to possible alterations in cerebral blood flow. This paper investigates the possible etiology of this particular phenomenon, and presents a simple analytical model that could explain the changes in intracranial pressure. The model combines the effects of cerebral venous constriction, arterial dilatation, and raised mean blood pressure to yield the characteristic immediate rise and exponential decay of ICP. The main contributor to the increase in intracranial pressure is believed to be vasodilation of cerebral arteries following venous constriction. Passive release of cerebrospinal fluid (CSF) is believed to mediate the long-term decay of intracranial pressure and possibly contribute to local hyperemia. C1 UNIV PENN,DEPT BIOENGN,PHILADELPHIA,PA 19104. RP BOOCK, RJ (reprint author), NIH,SURG NEUROL BRANCH,BLDG 10-5D37,BETHESDA,MD 20892, USA. FU PHS HHS [R49 CCR 302265, R49 CCR 304684, R49 CCR 303681] NR 16 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV-DEC PY 1993 VL 21 IS 6 BP 645 EP 653 DI 10.1007/BF02368644 PG 9 WC Engineering, Biomedical SC Engineering GA MN227 UT WOS:A1993MN22700007 PM 8116916 ER PT J AU KRAMER, BS BROWN, ML PROROK, PC POTOSKY, AL GOHAGAN, JK AF KRAMER, BS BROWN, ML PROROK, PC POTOSKY, AL GOHAGAN, JK TI PROSTATE-CANCER SCREENING - WHAT WE KNOW AND WHAT WE NEED TO KNOW SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID DIGITAL RECTAL EXAMINATION; DETECTION-PROJECT; ANTIGEN LEVELS; MEN; CARCINOMA; MARKER; PROTEIN; DISEASE; SERUM AB Objective: To critically evaluate the evidence for recommending the screening of asymptomatic men for prostate cancer with a blood test to detect a prostate-specific antigen (PSA). Data Sources: Relevant articles on screening for prostate cancer were identified from MEDLINE searches, from the authors' files, and from the bibliographies of identified articles. Study Selection: In the absence of controlled prospective trials, the studies are primarily retrospective and contain information about the sensitivity, specificity, and predictive values of tests used to screen for prostate cancer; the natural history of untreated prostate cancer; the morbidity, mortality, and costs of definitive treatment; and reviews of screening study biases. Data Extraction: Potential treatment-related mortality and costs that could be incurred by screening were estimated using defined assumptions. Results: Although screening for prostate cancer has the potential to save lives, because of possible over-diagnosis, screening and subsequent therapy could actually have a net unfavorable effect on mortality or quality of life or both. Given the performance characteristics of the test, widespread screening efforts would probably cost billions of dollars. Conclusions: The net benefit from widespread screening is unclear. A randomized prospective study of the effect of screening on prostate cancer mortality has therefore been initiated by the National Cancer Institute. RP KRAMER, BS (reprint author), NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. NR 60 TC 219 Z9 222 U1 0 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1993 VL 119 IS 9 BP 914 EP 923 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA MD711 UT WOS:A1993MD71100009 PM 7692780 ER PT J AU FOULKES, MA DEYTON, LR ELLENBERG, SS AF FOULKES, MA DEYTON, LR ELLENBERG, SS TI COMMUNITY-BASED HIV TRIALS ARE RIGOROUS, SAYS NIH SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA,ROCKVILLE,MD. RP FOULKES, MA (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 4 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 NOV 1 PY 1993 VL 119 IS 9 BP 956 EP 957 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MD711 UT WOS:A1993MD71100027 PM 8215014 ER PT J AU KATZ, D TAUBENBERGER, JK CANNELLA, B MCFARLIN, DE RAINE, CS MCFARLAND, HF AF KATZ, D TAUBENBERGER, JK CANNELLA, B MCFARLIN, DE RAINE, CS MCFARLAND, HF TI CORRELATION BETWEEN MAGNETIC-RESONANCE-IMAGING FINDINGS AND LESION DEVELOPMENT IN CHRONIC, ACTIVE MULTIPLE-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DOSE INTRAVENOUS METHYLPREDNISOLONE; CENTRAL-NERVOUS-SYSTEM; GADOLINIUM-DTPA MRI; ENHANCEMENT; SERIAL; BRAIN; OLIGODENDROCYTES; ASTROCYTES; BREAKDOWN AB Magnetic resonance imaging is a highly sensitive method for the detection of the lesions of multiple sclerosis an renders possible the study and the evolution of early lesions. Previous reports on magnetic resonance imaging following gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) injection demonstrated that new lesions can be recognized by contrast enhancement. The pathological basis of these observations is uncertain. We have had the opportunity to study at autopsy the brain of a patient with chronic progressive multiple sclerosis who suffered acute worsening leading to death. Magnetic resonance imaging performed 10 days and 4 weeks prior to death showed new Gd-DTPA-enhanced lesions in the posterior hemispheric white matter adjacent to the lateral ventricles. Light microscopic examination of these areas demonstrated them to be fresh lesions comprising intense inflammatory activity and dense perivascular cuffs within an edematous lesion center and a striking parenchymal mononuclear cell infiltration at the margins of the lesions. Lesions that were demonstrated by increased signal on T2-weighted images, but were not enhanced following administration of Gd-DTPA, were all of the chronic type, either inactive or active. None of these showed the intense inflammatory activity of the acute lesions and most displayed fibrous astrogliosis. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL NEUROPATHOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. ROSE F KENNEDY CTR RES MENTAL RETARDAT & HUMAN DEV,BRONX,NY. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 08952, NS 11920] NR 29 TC 352 Z9 354 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1993 VL 34 IS 5 BP 661 EP 669 DI 10.1002/ana.410340507 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA MG096 UT WOS:A1993MG09600006 PM 8239560 ER PT J AU BATSHAW, ML ROBINSON, MB HYLAND, K DJALI, S HEYES, MP AF BATSHAW, ML ROBINSON, MB HYLAND, K DJALI, S HEYES, MP TI QUINOLINIC ACID IN CHILDREN WITH CONGENITAL HYPERAMMONEMIA SO ANNALS OF NEUROLOGY LA English DT Article ID METHYL-D-ASPARTATE; CEREBROSPINAL-FLUID; LIQUID-CHROMATOGRAPHY; UREA SYNTHESIS; INBORN-ERRORS; RAT-BRAIN; TRYPTOPHAN; TETRAHYDROBIOPTERIN; ENCEPHALOPATHY; NEUROTOXICITY AB Levels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammonemia. Twofold to tenfold elevations of QUIN were found in 4 neonates in hyperammonemic coma (QUIN range, 250-990 nM; control mean, 110 +/- 90 nM; p < 0.005). Similar elevations of neopterin were found (range, 24-75 nM; control mean, 9.0 +/- 4.9 nM; p < 0.005). In addition, significant elevations of QUIN were found in 14 older children with congenital hyperammonemia (mean, 50 +/- 20 vs 17 +/- 6 nM; p < 0.05). Neopterin levels were not elevated in these children. The QUIN may originate from an increase in tryptophan transport across the blood-brain barrier or from induction of indolamine-2,3-dioxygenase activity. These findings support a role for QUIN in the neuropathology of congenital hyperammonemia. They also suggest the potential utility of N-methyl-D-aspartate receptor-blocking agents or inhibitors of QUIN synthesis in the treatment of hyperammonemic coma. C1 BAYLOR RES INST,CTR METAB DIS,DALLAS,TX. NIH,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,CHILDRENS HOSP PHILADELPHIA,SCH MED,PHILADELPHIA,PA 19104. FU NICHD NIH HHS [P-30-HD26979]; NINDS NIH HHS [R01-NS 28033] NR 30 TC 42 Z9 42 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1993 VL 34 IS 5 BP 676 EP 681 DI 10.1002/ana.410340509 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA MG096 UT WOS:A1993MG09600008 PM 7694541 ER PT J AU GUADAGNI, F ROSELLI, M COSIMELLI, M FERRONI, P SPILA, A CASALDI, V CAVALIERE, F CARLINI, M GAROFALO, A RINALDI, G SANTORO, E GREINER, JW SCHLOM, J AF GUADAGNI, F ROSELLI, M COSIMELLI, M FERRONI, P SPILA, A CASALDI, V CAVALIERE, F CARLINI, M GAROFALO, A RINALDI, G SANTORO, E GREINER, JW SCHLOM, J TI CORRELATION BETWEEN POSITIVE CA-72-4 SERUM LEVELS AND LYMPH-NODE INVOLVEMENT IN PATIENTS WITH GASTRIC-CARCINOMA SO ANTICANCER RESEARCH LA English DT Article DE MONOCLONAL ANTIBODIES; TUMOR-ASSOCIATED GLYCOPROTEIN-72 CA 72-4 ASSAY; SERUM TUMOR MARKERS, GASTRIC CANCER; LYMPH NODE AND SEROSAL INVOLVEMENT ID TUMOR-ASSOCIATED ANTIGEN; GASTROINTESTINAL CARCINOMA; CA-19-9; CANCER; TAG-72; MARKER; MORTALITY; ASSAY; CEA AB CA 72-4 serum marker has been shown to be one of the most specific and sensitive markers for monitoring gastric cancel. In the present study we evaluated the correlation between CA 72-4, CA 19-9 and CEA serum levels, and tumor size and lymph node involvement in gastric carcinoma patients. One-hundred sixty-one patients with primary or recurrent gastric carcinoma were studied. Elevated CA 72-4, CA 19-9, nod CEA serum levels wer e found in 42.2%, 32.3% and 24.2%, respectively. As previously shown, the combination of CA 72-4 and CA 19-9 increased positive samples to 56.5%, while the addition of CEA did not further improve this percentage. Unlike what has been previously published, none of the markers showed a significant correlation with serosal involvement. In fact, elevated serum levels were observed for the thr ee markers in a very low percentage of cases either in T1-T2N0 or T3-T4N0 patients. In contrast, CA 72-4 showed a highly significant correlation with lymph node involvement: T1-T4N0 patients had positive CA 72-4 levels in 5 out of 37 (13.5%), while T1-T4N1 in 12 out of 32 (37.5%), and T1-T4N2 in 20 out of 40 (50%) (p<0.003). CA 19-9 and CEA serum levels wets not significantly correlated. Since the presence of lymph node metastases is considered a negative prognostic factor, these, results suggest that the measurement of CA 72-4 serum levels may be an important parameter in the diagnosis and clinical follow-up of patients with gastric carcinoma cinoma. C1 UNIV ROMA TOR VERGATA,DEPT SURG,ROME,ITALY. REGINA ELENA INST CANC RES,DEPT SURG 1,ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00185 ROME,ITALY. REGINA ELENA INST CANC RES,DEPT SURG 2,I-00161 ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP GUADAGNI, F (reprint author), REGINA ELENA INST CANC RES,CLIN PATHOL LAB,VIALE REGINA ELENA 291,I-00161 ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016; OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648; Ferroni, Patrizia/0000-0002-9877-8712 NR 18 TC 15 Z9 15 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 NOV-DEC PY 1993 VL 13 IS 6B BP 2409 EP 2413 PG 5 WC Oncology SC Oncology GA NE372 UT WOS:A1993NE37200010 PM 8135475 ER PT J AU KOHN, EC AF KOHN, EC TI DEVELOPMENT AND PREVENTION OF METASTASIS SO ANTICANCER RESEARCH LA English DT Article DE METASTASIS; DEVELOPMENT; PREVENTION ID NUCLEOSIDE DIPHOSPHATE KINASE; AUTOCRINE MOTILITY FACTOR; BASEMENT-MEMBRANE COLLAGEN; HUMAN-MELANOMA CELLS; IV COLLAGENASE; GROWTH-FACTOR; PERTUSSIS TOXIN; BREAST-CANCER; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR AB Metastatic spread of malignancy is the primary cause of treatment failure and subsequent death in cancer patients. All cancers have the capability to metastasize, however, there are notable exceptions which rarely if ever metastasize. These include basal cell carcinoma, or cancers which are primarily locally invasive such as primary brain cancers. Is metastasis is an earlier process in cancer progression than originally hypothesized? Over 70% of patients have occult or overt metastatic disease at the time of presentation. Thus, the overwhelming proportion of patients have disease which is not surgically resectable for core at the time of diagnosis. Metastasis is a continuous process commencing early in the growth of the primary tumor before it is clinically detectable by the most sensitive of means (1-6). In addition, metastases have the propensity to metastasize. The size and age variation in metastases, their dispersed anatomic locations, the local vascular and lymphatic environment, and their heterogeneous composition hinder complete surgical extirpation of disease and limit the effective concentration of anticancer drugs that can be delivered to metastatic colonies (7,8). RP KOHN, EC (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 75 TC 28 Z9 28 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 NOV-DEC PY 1993 VL 13 IS 6B BP 2553 EP 2559 PG 7 WC Oncology SC Oncology GA NE372 UT WOS:A1993NE37200032 PM 7510940 ER PT J AU CARLSTEAD, K BROWN, JL STRAWN, W AF CARLSTEAD, K BROWN, JL STRAWN, W TI BEHAVIORAL AND PHYSIOLOGICAL CORRELATES OF STRESS IN LABORATORY CATS SO APPLIED ANIMAL BEHAVIOUR SCIENCE LA English DT Article DE ACTH; CORTISOL; PREDICTABILITY; CARETAKING ROUTINE; HIDING BEHAVIOR; EXPLORATORY BEHAVIOR; CATS ID LUTEINIZING-HORMONE; GONADAL RESPONSE; OVARIAN-FUNCTION; ANIMAL-WELFARE; DOMESTIC CAT; FELIS-CATUS; DAIRY-COWS; PITUITARY; ADRENOCORTICOTROPIN; CORTISOL AB Sixteen domestic cats were used to investigate the pituitary-adrenal, pituitary-gonadal and behavioral consequences of an unpredictable handling and husbandry routine. After a 10-day baseline period of standard laboratory procedures, eight cats ('stressed cats', STR) were subjected to a 21-day period of altered caretaking characterized by irregular feeding and cleaning times, absence of talking and petting by humans, and daily unpredictable manipulations. Eight control cats (CON group) were maintained for 21 days on the standard caretaking schedule. Behavior was recorded on time-lapse video 24 h day-1, urine was collected daily for cortisol analyses, and hormone stimulation tests with synthetic adrenocorticotropic hormone (ACTH) and luteinizing hormone-releasing hormone (LHRH) were conducted before and after the 3-week treatment period. Results indicate that the STR cats were chronically stressed by the altered caretaking routine. Urinary cortisol concentrations were consistently elevated throughout the 3-week period, adrenal sensitivity to ACTH was enhanced and pituitary sensitivity to LHRH was reduced. Active exploratory and play behavior was suppressed, and STR cats spent more time awake/alert and attempting to hide. Hiding was negatively correlated with cortisol concentration and, therefore, may be an important behavior for coping with uncontrollable and unpredictable captive environments. These results indicate that qualitatively poor caretaking is a potent psychological stressor for confined cats that may eventually compromise reproduction through behavioral or physiological mechanisms. To promote well-being, caged cats should be provided with appropriate places for concealment. C1 NATL INST MENTAL HLTH,POOLESVILLE,MD 20837. RP CARLSTEAD, K (reprint author), SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008, USA. NR 84 TC 135 Z9 141 U1 5 U2 61 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1591 J9 APPL ANIM BEHAV SCI JI Appl. Anim. Behav. Sci. PD NOV PY 1993 VL 38 IS 2 BP 143 EP 158 DI 10.1016/0168-1591(93)90062-T PG 16 WC Agriculture, Dairy & Animal Science; Behavioral Sciences; Veterinary Sciences SC Agriculture; Behavioral Sciences; Veterinary Sciences GA MJ860 UT WOS:A1993MJ86000004 ER PT J AU KELMAN, DJ MASON, RP AF KELMAN, DJ MASON, RP TI CHARACTERIZATION OF THE RAT HEMOGLOBIN THIYL FREE-RADICAL FORMED UPON REACTION WITH PHENYLHYDRAZINE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID RED-BLOOD-CELLS; LIPID-PEROXIDATION; INVIVO; EPOXIDATION; MYOGLOBIN C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. RP KELMAN, DJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 15 Z9 15 U1 1 U2 5 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 NOV 1 PY 1993 VL 306 IS 2 BP 439 EP 442 DI 10.1006/abbi.1993.1535 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MC834 UT WOS:A1993MC83400022 PM 8215448 ER PT J AU STANLEY, JR AF STANLEY, JR TI SHOULD YOU THROW AWAY THIS ISSUE SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material RP STANLEY, JR (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1993 VL 129 IS 11 BP 1398 EP 1400 DI 10.1001/archderm.129.11.1398 PG 3 WC Dermatology SC Dermatology GA MG677 UT WOS:A1993MG67700003 PM 7694549 ER PT J AU VOGEL, JC AF VOGEL, JC TI KERATINOCYTE GENE-THERAPY SO ARCHIVES OF DERMATOLOGY LA English DT Article ID DYSTROPHIC EPIDERMOLYSIS-BULLOSA; HUMAN EPIDERMAL-KERATINOCYTES; MODIFIED SKIN FIBROBLASTS; TRANSGENIC MICE; XERODERMA-PIGMENTOSUM; APOLIPOPROTEIN-E; GROWTH-HORMONE; STEM-CELLS; FACTOR-IX; EXPRESSION AB Background: Gene therapy is currently being used in clinical trials to treat a variety of diseases. In keratinocyte gene therapy, the gene that will correct the disease by expressing the normal protein or enzyme is inserted and expressed in keratinocytes. Keratinocytes have significant potential, as a. target cell of gene therapy, in the treatment of both systemic diseases as well as skin diseases caused by a genetic defect in keratinocytes. Observations: Although keratinocyte gene therapy is not yet being tested in clinical trials, animal models do exist where keratinocytes are being used to secrete factors such as human growth hormone and factor IX (for hemophilia) into the systemic circulation. Genetic diseases of the skin such as recessive epidermolysis bullosa dystrophica or xeroderma pigmentosum have not yet been treated with keratinocyte gene therapy in animal models. Conclusions: Keratinocytes have many advantages as a target cell in gene therapy, and progress has been made using animal models. However, the sustained and efficient delivery of factors to the bloodstream by keratinocytes expressing a transgene has not yet been accomplished. Future goals are to obtain adequate levels of the desired factors, hormones, or enzymes for sustained periods of time, either in keratinocytes or in the vascular system. RP VOGEL, JC (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 52 TC 39 Z9 39 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1993 VL 129 IS 11 BP 1478 EP 1483 DI 10.1001/archderm.129.11.1478 PG 6 WC Dermatology SC Dermatology GA MG677 UT WOS:A1993MG67700013 PM 8239704 ER PT J AU SHORE, DL SANDLER, DP DAVEY, FR MCINTYRE, OR BLOOMFIELD, CD AF SHORE, DL SANDLER, DP DAVEY, FR MCINTYRE, OR BLOOMFIELD, CD TI ACUTE-LEUKEMIA AND RESIDENTIAL PROXIMITY TO POTENTIAL SOURCES OF ENVIRONMENTAL-POLLUTANTS SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID LUNG-CANCER; EXPOSURE; PLANTS; POLAND AB Possible associations between location of residence and acute leukemia risk were investigated in a study of 610 newly diagnosed patients, aged 18-79 y, and 618 population controls. There was an association between ever living within 5 miles (8 km) of an industrial plant and leukemia risk, with adjusted odds ratios (ORs) of 1.4 (95% confidence interval [95% CI] = 1.0-1.9) for all acute leukemias combined, 1.4 (95% CI = 1.0-2.0) for acute myeloid leukemia, and 1.7 (95% CI = 1.0-2.7) for acute lymphocytic leukemia. Odds ratios increased with decreasing distance from industrial sites, but a gradient with duration of residence was seen only among those less than age 60 who had lived within a mile of any industry. Suggestive associations were also observed for residence near specific industries, but the number of individuals living near any one industry was small. C1 NIEHS,EPIDEMIOL BRANCH,ENVIRONM & MOLEC EPIDEMIOL SECT,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709. WESTAT CORP,DURHAM,NC. SUNY HLTH SCI CTR,SYRACUSE,NY. DARTMOUTH COLL,HITCHCOCK MED CTR,CANC & LEUKEMIA GRP B,HANOVER,NH 03756. ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA33601, CA37027, CA31946] NR 17 TC 17 Z9 17 U1 0 U2 3 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 NOV-DEC PY 1993 VL 48 IS 6 BP 414 EP 420 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA MK137 UT WOS:A1993MK13700005 PM 8250593 ER PT J AU LEIBENLUFT, E DIAL, TH HAVILAND, MG PINCUS, HA AF LEIBENLUFT, E DIAL, TH HAVILAND, MG PINCUS, HA TI SEX-DIFFERENCES IN RANK ATTAINMENT AND RESEARCH ACTIVITIES AMONG ACADEMIC PSYCHIATRISTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID INTERNAL-MEDICINE; MEN FACULTY; WOMEN; DEPARTMENTS; RADIOLOGY; SCIENCE; TIME AB Data from a survey distributed to all full-time faculty in-academic departments of psychiatry were used to examine possible sex differences in research activities and rank attainment among psychiatrists. A total of 1923 psychiatrists responded, 1564 men (81.3%) and 359 women (18.7%). Continuous dependent variables were analyzed by using analyses of covariance with the year graduated from medical school as a covariate. For categorical dependent variables, the sample was divided into four 10-year cohorts based on the year graduated from medical school, and differences between men and women were analyzed with chi2 tests. Over the entire sample, men were more likely than women to have had research training, to have ever been principal investigators on peer-reviewed grants, to mentor research trainees, to be currently involved in research activities, and to meet defined criteria as a ''researcher.'' Many gender differences remained significant after controlling for seniority and research training. In every cohort, the men had attained higher academic rank than the women. In general, differences in research activity and productivity were most marked in the youngest cohort. To ensure a rich talent pool for psychiatric research, efforts must be made to recruit and support researchers from among the increased number of women in psychiatry. C1 HLTH INSURANCE ASSOC AMER POLICY DEV & RES DEPT,WASHINGTON,DC. LOMA LINDA UNIV,SCH MED,DEPT PSYCHIAT,LOMA LINDA,CA 92354. AMER PSYCHIAT ASSOC,OFF RES,WASHINGTON,DC 20009. RP LEIBENLUFT, E (reprint author), NIMH,CLIN PSYCHOBIOL GRP,BLDG 10,ROOM 45-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1993 VL 50 IS 11 BP 896 EP 904 PG 9 WC Psychiatry SC Psychiatry GA MG306 UT WOS:A1993MG30600006 PM 8215815 ER PT J AU CAO, GH CUTLER, RG AF CAO, GH CUTLER, RG TI HIGH-CONCENTRATIONS OF ANTIOXIDANTS MAY NOT IMPROVE DEFENSE AGAINST OXIDATIVE STRESS SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE ASCORBIC ACID; ALPHA-TOCOPHEROL; URIC ACID; TROLOX; OXYGEN-RADICAL ID LOW-DENSITY-LIPOPROTEIN; PLASMA VITAMIN-E; HYDROGEN-PEROXIDE; ERYTHROCYTE-MEMBRANES; LIPID-PEROXIDATION; HYDROXYL RADICALS; ALPHA-TOCOPHEROL; DNA DAMAGE; COPPER; INACTIVATION AB It is often assumed that the oxygen radical defense could be further improved by higher concentration of antioxidants. But this has not been demonstrated over a wide range of concentrations. There are different types of oxygen radicals produced in the body and the antioxidant protection against them may not positively related to their concentrations. We report here that by using H2O2 With Cu2+ as an hydroxyl-radical generator in vitro, ascorbic acid shows no oxygen-radical absorbing capacity. We also found that the net hydroxyl-radical absorbing capacity of a water soluble alpha-tocopherol analogue (Trolox) and uric acid increases with concentration only when the concentration is lower than the normal value found for alpha-tocopherol and uric acid in human serum. At higher concentrations, the hydroxyl-radical absorbing capacity of the alpha-tocopherol analogue and uric acid decreases. The mechanism involved in the decrease of hydroxyl radical absorbance capacity of Trolox and uric acid at high concentration may be related to their reaction with hydroxyl radicals or other oxygen radicals produced in the presence of both H2O2 and Cu2+. This kind of reaction could lead to the formation of additional many Trolox or uric acid radicals at the same time. These results may be important not only in evaluating antioxidant activities of antioxidants in vitro but also in studying the potential efficiency of antioxidants in vivo in affecting oxidative stress status. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 31 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD NOV-DEC PY 1993 VL 17 IS 3 BP 189 EP 201 DI 10.1016/0167-4943(93)90050-R PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MU924 UT WOS:A1993MU92400004 PM 15374318 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI RETROVIRUSES AND INFLAMMATORY MYOPATHIES IN HUMANS AND PRIMATES SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY ANALYSIS; HIV-INFECTION; HTLV-I; PERIPHERAL NEUROPATHY; MONONUCLEAR-CELLS; MITOCHONDRIAL-DNA; MYASTHENIA-GRAVIS; POLYMYOSITIS; MUSCLE RP DALAKAS, MC (reprint author), NIH,NEUROMUSCULAR DIS SECT,BLDG 10,ROOM 4N248,BETHESDA,MD 20892, USA. NR 87 TC 17 Z9 17 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD NOV PY 1993 VL 2 IS 3 BP 659 EP 691 PG 33 WC Clinical Neurology SC Neurosciences & Neurology GA MK330 UT WOS:A1993MK33000009 PM 8156147 ER PT J AU RUBENSTEIN, CS PEYNIRCIOGLU, ZF CHAMBLESS, DL PIGOTT, TA AF RUBENSTEIN, CS PEYNIRCIOGLU, ZF CHAMBLESS, DL PIGOTT, TA TI MEMORY IN SUBCLINICAL OBSESSIVE-COMPULSIVE CHECKERS SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID DISORDER; DEFICITS AB In a series of experiments we extended the research on possible memory deficits in subclinical obsessive-compulsive Ss who reported excessive checking. Using a variety of memory tests we compared 20 subclinical checkers to 20 Ss without obsessive-compulsive symptomatology. Contrary to hypothesis, checkers remembered self-generated words better than read words just as much as did normals, but they were more likely than normals to report thinking they had studied words that, in fact, had not been on the study list. Further, they more often confused whether they read or generated the words at study. Checkers did not appear to perseverate on already-recalled words on repeated free recall tests any more than did normals. However, checkers remembered fewer actions overall and more often misremembered whether they had performed, observed, or written these actions. Such memory deficits may contribute to the development of excessive checking. C1 GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20007. NIMH,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. RP RUBENSTEIN, CS (reprint author), AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC 20016, USA. NR 15 TC 54 Z9 54 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD NOV PY 1993 VL 31 IS 8 BP 759 EP 765 DI 10.1016/0005-7967(93)90006-G PG 7 WC Psychology, Clinical SC Psychology GA MB265 UT WOS:A1993MB26500006 PM 8257407 ER PT J AU MERRICK, BA WITCHER, LL PATTERSON, RM HE, CY SELKIRK, JK AF MERRICK, BA WITCHER, LL PATTERSON, RM HE, CY SELKIRK, JK TI IDENTIFICATION OF 2 ISOFORMS OF PHOSPHOLIPASE-C-ALPHA FROM DIVIDING MURINE FIBROBLASTS BY PROTEIN MICROSEQUENCING SO BIOCHEMICAL ARCHIVES LA English DT Article ID PURIFICATION; SEQUENCES; ISOZYMES; ESTROGEN; HIP-70 AB Growth responsive proteins were studied in cultured murine C3H10T1/2 fibroblasts. Two-dimensional gel electrophoresis (2D PAGE) of radiolabeled cells revealed several proteins apparent during log growth which were absent under non-dividing conditions, including two cytosolic 62 kD proteins. Of these two growth responsive proteins, both were present in growing cells but only the more acidic protein was present during the resting state. These two 62 kD proteins were resolved by charge (pI = 6.2 and 6.3) using preparative 2D PAGE, electroblotted, sequenced and identified as two phospholipase C-alpha isoforms. Both proteins shared an identical amino terminal sequence for 14 residues which matched the known predicted sequence for PLC-alpha from cDNA clones. The two isoforms are phosphorylated and dephosphorylated forms of the enzyme. The finding of serine at the amino terminus, 24 residues from the amino terminus predicted from cDNA, is consistent with the presence of an amino terminal signal sequence and proteolytic processing. RP NIEHS, MOLEC CARCINOGENESIS LAB, RES TRIANGLE PK, NC 27709 USA. NR 18 TC 5 Z9 6 U1 0 U2 0 PU MBR PRESS INC PI KENYON PA PO BOX P, KENYON, MN 55946-000P USA SN 0749-5331 J9 BIOCHEM ARCH JI Biochem. Arch. PD NOV PY 1993 VL 9 IS 4 BP 335 EP 340 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG408 UT WOS:A1993MG40800009 ER PT J AU PADLAN, EA HELM, BA AF PADLAN, EA HELM, BA TI MODELING STUDY OF IGE/RECEPTOR INTERACTIONS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 647th Meeting of the Biochemical-Society CY JUL 20-23, 1993 CL UNIV SHEFFIELD, SHEFFIELD, UNITED KINGDOM SP BIOCHEM SOC HO UNIV SHEFFIELD ID HIGH-AFFINITY RECEPTOR; EPSILON-RII CD23; IMMUNOGLOBULIN-E; IGE RECEPTOR; ALPHA-SUBUNIT; FC; BINDING; LIGAND; CELLS C1 UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,DEPT MOLEC BIOL & BIOTECHNOL,SHEFFIELD S10 2UH,ENGLAND. RP PADLAN, EA (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1993 VL 21 IS 4 BP 963 EP 967 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN412 UT WOS:A1993MN41200033 PM 8132101 ER PT J AU HENDERSON, PJF ROBERTS, PE MARTIN, GEM SEAMON, KB WALMSLEY, AR RUTHERFORD, NG VARELA, MF GRIFFITH, JK AF HENDERSON, PJF ROBERTS, PE MARTIN, GEM SEAMON, KB WALMSLEY, AR RUTHERFORD, NG VARELA, MF GRIFFITH, JK TI HOMOLOGOUS SUGAR-TRANSPORT PROTEINS IN MICROBES AND MAN SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 647th Meeting of the Biochemical-Society CY JUL 20-23, 1993 CL UNIV SHEFFIELD, SHEFFIELD, UNITED KINGDOM SP BIOCHEM SOC HO UNIV SHEFFIELD ID ESCHERICHIA-COLI; DNA-SEQUENCE; GENE; REQUIREMENTS; CLONING; ENCODES; SYSTEM; SV2 C1 UNIV NEW MEXICO,SCH MED,CTR CANC,DEPT CELL BIOL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,CTR CANC,DEPT MICROBIOL,ALBUQUERQUE,NM 87131. NIH,BETHESDA,MD 20892. UNIV EDINBURGH,INST CELL ANIM & POPULAT BIOL,EDINBURGH EH9 3JT,MIDLOTHIAN,SCOTLAND. UNIV SHEFFIELD,DEPT MOLEC BIOL & BIOTECHNOL,SHEFFIELD S10 2UH,ENGLAND. RP HENDERSON, PJF (reprint author), UNIV LEEDS,DEPT BIOCHEM & MOLEC BIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. RI Varela, Manuel/A-7782-2009 OI Varela, Manuel/0000-0001-8667-7853 FU NIGMS NIH HHS [MRC5-T34-GM08222, 2-SO6-GM08139]; Wellcome Trust NR 25 TC 11 Z9 13 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1993 VL 21 IS 4 BP 1002 EP 1006 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN412 UT WOS:A1993MN41200041 PM 8131886 ER PT J AU CRESPI, CL PENMAN, BW GONZALEZ, FJ GELBOIN, HV GALVIN, M LANGENBACH, R AF CRESPI, CL PENMAN, BW GONZALEZ, FJ GELBOIN, HV GALVIN, M LANGENBACH, R TI GENETIC TOXICOLOGY USING HUMAN CELL-LINES EXPRESSING HUMAN P-450 SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 647th Meeting of the Biochemical-Society CY JUL 20-23, 1993 CL UNIV SHEFFIELD, SHEFFIELD, UNITED KINGDOM SP BIOCHEM SOC HO UNIV SHEFFIELD ID HUMAN-LIVER; METABOLIC-ACTIVATION; HUMAN LYMPHOBLAST; HUMAN CYTOCHROME-P450IA2; STABLE EXPRESSION; MUTATION ASSAYS; TOBACCO-SMOKE; AFLATOXIN-B1; ENZYME; CDNA C1 NIEHS,RES TRIANGLE PK,NC 27709. NCI,BETHESDA,MD 20892. RP CRESPI, CL (reprint author), GENTEST CORP,6 HENSHAW ST,WOBURN,MA 01801, USA. NR 29 TC 15 Z9 15 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1993 VL 21 IS 4 BP 1023 EP 1028 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN412 UT WOS:A1993MN41200046 PM 8131891 ER PT J AU ZAHAREVITZ, DW CHISENA, CA DUNCAN, KLK AUGUST, EM CYSYK, RL AF ZAHAREVITZ, DW CHISENA, CA DUNCAN, KLK AUGUST, EM CYSYK, RL TI VANADATE INHIBITION OF HYALURONIC-ACID SYNTHESIS IN SWISS 3T3 FIBROBLASTS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID GLYCOSAMINOGLYCAN SYNTHESIS; CULTURES; PROTEOGLYCAN; ESTROGEN; CELLS RP ZAHAREVITZ, DW (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Duncan, Kimberly /C-3655-2013 NR 19 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD NOV PY 1993 VL 31 IS 4 BP 627 EP 633 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK105 UT WOS:A1993MK10500003 PM 7507761 ER PT J AU LESIAK, K KHAMNEI, S TORRENCE, PF AF LESIAK, K KHAMNEI, S TORRENCE, PF TI 2',5'-OLIGOADENYLATE - ANTISENSE CHIMERAS SYNTHESIS AND PROPERTIES SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CHEMICAL SYNTHESIS; INTERFERON ACTION; TARGETED CLEAVAGE; ESCHERICHIA-COLI; MESSENGER-RNA; STRANDED-DNA; SEQUENCE; OLIGONUCLEOTIDES; OLIGORIBONUCLEOTIDES; BINDING AB We have synthesized a novel bioconjugate which joins an antisense oligonucleotide to a unique and potent inhibitor of translation, p(n)5'A2'(p5'A2')(m)p5'A(2-5A). Two residues of 4-hydroxybutyl phosphate were employed as linkers to attach the 2',5'-oligoadenylate moiety through its 2'-terminus to the 5'-terminus of the chosen antisense sequence, (dT)20. The syntheses were carried on a solid support according to the phosphite triester method of DNA synthesis (Letsinger, R. L., and Lunsford, W. B. (1976) J. Am. Chem. Soc. 98, 3655-3661; Beaucage, S. L., and Caruthers, M. H. (1981) Tetrahedron Lett. 22, 1859-1862). The generated 2-5A antisense chimeras retained both the ability of the 2-5A molecule to activate the 2-5A-dependent RNase as well as the ability of the oligo(dT) moiety to hybridize to the complementary poly(A). Moreover, the chimera, when annealed to its target nucleic acid sequence, was still effectively bound to the 2-5A-dependent nuclease. The methodology described represents a new approach to the selective modulation of mRNA expression. C1 NIDDKD,BIOMED CHEM SECT,MED CHEM LAB,BLDG 8,ROOM B2A02,BETHESDA,MD 20892. NR 42 TC 40 Z9 40 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1993 VL 4 IS 6 BP 467 EP 472 DI 10.1021/bc00024a008 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA MK939 UT WOS:A1993MK93900008 PM 8305516 ER PT J AU KREITMAN, RJ PASTAN, I AF KREITMAN, RJ PASTAN, I TI PURIFICATION AND CHARACTERIZATION OF IL6-PE(4E), A RECOMBINANT FUSION OF INTERLEUKIN-6 WITH PSEUDOMONAS EXOTOXIN SO BIOCONJUGATE CHEMISTRY LA English DT Note ID GROWTH-FACTOR ALPHA; TUMOR-CELLS; RECEPTOR; PROTEIN; DOMAINS; CYTOTOXICITY; RENATURATION; EXPRESSION; CARCINOMA; MYELOMA AB We have developed a procedure to purify the recombinant fusion toxin IL6-PE4E from Escherichia coli which results in a high yield of fully active monomeric protein of high purity and very low endotoxin content. The chimeric toxin is composed of human interleukin 6 (IL6) fused to a derivative of Pseudomonas exotoxin (PE) containing mutations in the binding domain which prevent binding to the PE receptor. In a typical preparation, 20 g of E. coli cells expressing the plasmid encoding IL6-PE4E were treated with lysozyme and washed repeatedly with detergent (Triton X-100), to obtain 500 mg of inclusion bodies. The recombinant protein was denatured and reduced in guanidine hydrochloride solution containing dithioerythritol and refolded in a redox buffer containing oxidized glutathione and L-arginine. After purification of the dialyzed protein by anion-exchange, polymyxin B, and sizing chromatography, we obtained 100 mg (20% of recombinant protein) of purified monomer with 0.6-2.5 endotoxin units/mg of protein. Amino terminal sequencing confirmed the first 20 amino acids. IL6-PE4E purified in this manner was fully cytotoxic toward human multiple myeloma, hepatoma, epidermoid carcinoma, and prostate carcinoma cell lines. After intravenous injection into mice, we found the dose-limiting toxicity to be to the liver, by measurement of serum transaminases and histologic evaluation of the liver. The LD50 was 450 mug/kg. We conclude that IL6-PE4E can be purified efficiently for preclinical testing. C1 NCI,DIV CANC BIOL DIAGNOSIS & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 23 TC 22 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1993 VL 4 IS 6 BP 581 EP 585 DI 10.1021/bc00024a025 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA MK939 UT WOS:A1993MK93900025 PM 8305530 ER PT J AU DIMITROV, DS AF DIMITROV, DS TI KINETIC MECHANISMS OF MEMBRANE-FUSION MEDIATED BY ELECTRIC-FIELDS SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Review ID THIN LIQUID-FILMS; HAMSTER OVARY CELLS; LIPID BILAYERS; MAMMALIAN-CELLS; INFLUENZA HEMAGGLUTININ; INSOLUBLE MONOLAYERS; ERYTHROCYTE-GHOSTS; PLANT-PROTOPLASTS; PHASE-TRANSITION; INITIAL-STAGES AB External electric fields can induce the fusion of a wide variety of cell and artificial membranes. This experimental observation is a demonstration of an inherent ability of membranes to fuse if appropriate conditions are provided, and indicates the existence of properties of membrane systems, related to fusion, which are largely independent of the type of membrane. An approach to understanding more clearly the fundamental properties of membranes needed for fusion involves the comparison of systems of different levels of complexity, such as lipid monolayers, bilayers and plasma cell membranes. In all of these systems the physicochemical properties, especially viscosity, of the interacting membranes and the liquid layer between them are critical for the fusion kinetics. Other critical phenomenological parameters are the strength and duration of the electric pulse, which drives the fusion reaction. The fusogenic pulse induces a state of high Gibbs energy which leads to the destabilization of the membranes and the liquid layer between them by stochastic processes of growth of fluctuational waves and the overcoming of energy barriers. This results in the formation of localized molecular contacts, fusion junctions and pores, which may subsequently expand. Although this major kinetic pathway can be generally understood in terms of phenomenological models, the molecular mechanisms of electrofusion are unclear because of a lack of direct experimental measurements of the structural rearrangements during membrane merging. The elucidation of electrofusion mechanisms may provide clues to the understanding of the fundamental mechanisms of fusion in biological systems. C1 BULGARIAN ACAD SCI,CENT LAB BIOPHYS,BU-1113 SOFIA,BULGARIA. RP DIMITROV, DS (reprint author), NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892, USA. NR 108 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD NOV PY 1993 VL 32 IS 2 BP 99 EP 124 DI 10.1016/0302-4598(93)80029-T PG 26 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ME397 UT WOS:A1993ME39700001 ER PT J AU TANCER, ME STEIN, MB UHDE, TW AF TANCER, ME STEIN, MB UHDE, TW TI GROWTH-HORMONE RESPONSE TO INTRAVENOUS CLONIDINE IN SOCIAL PHOBIA - COMPARISON TO PATIENTS WITH PANIC DISORDER AND HEALTHY-VOLUNTEERS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE GROWTH HORMONE; SOMATOTROPIN; ANXIETY; PANIC DISORDER; SOCIAL PHOBIA ID ALPHA-2-ADRENOCEPTOR SENSITIVITY; NORADRENERGIC FUNCTION; GH RESPONSE; DEPRESSION; ANXIETY; GRF AB The growth hormone (GH) response to intravenous administration of clonidine hydrochloride (2 mug/kg) was assessed in 16 patients with DSM-III-R social phobia, 13 patients with DSM-III-R panic disorder, and 31 healthy controls. Compared to the healthy volunteers, both social phobic and panic-disorder patients had significantly blunted GH increments after clonidine. The social phobic patients demonstrated a similar degree of GH ''blunting'' to clonidine as did the patients with panic disorder. C1 NIMH,INTRAMURAL RES PROGRAM,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NR 28 TC 36 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1993 VL 34 IS 9 BP 591 EP 595 DI 10.1016/0006-3223(93)90150-C PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MH048 UT WOS:A1993MH04800002 PM 8292687 ER PT J AU MURPHY, DGM DECARLI, CD DALY, E GILLETTE, JA MCINTOSH, AR HAXBY, JV TEICHBERG, D SCHAPIRO, MB RAPOPORT, SI HORWITZ, B AF MURPHY, DGM DECARLI, CD DALY, E GILLETTE, JA MCINTOSH, AR HAXBY, JV TEICHBERG, D SCHAPIRO, MB RAPOPORT, SI HORWITZ, B TI VOLUMETRIC MAGNETIC-RESONANCE-IMAGING IN MEN WITH DEMENTIA OF THE ALZHEIMER-TYPE - CORRELATIONS WITH DISEASE SEVERITY SO BIOLOGICAL PSYCHIATRY LA English DT Article DE MAGNETIC RESONANCE IMAGING; ALZHEIMERS DISEASE; AGE; DEMENTIA SEVERITY; BRAIN ATROPHY; CEREBROSPINAL FLUID; CAUDATE NUCLEUS; LENTICULAR NUCLEUS; THALAMUS ID COMPUTED-TOMOGRAPHY; SENILE DEMENTIA; CEREBROSPINAL-FLUID; NEUROFIBRILLARY TANGLES; PATHOLOGICAL-CHANGES; PRESENILE-DEMENTIA; VENTRICULAR VOLUME; CEREBRAL ATROPHY; CORTICAL ATROPHY; HEALTHY-MEN AB Using magnetic resonance imaging (MRI), we measured the volumes of various brain structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5 moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF volumes were normalized as a percent of the traced intracranial volume to control for the relation of volumes of cerebral structures to head size, and analyzed statistically. The whole group of DAT subjects had significantly smaller mean cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly, larger mean ventricular and temporal lobe peripheral CSF volumes than did controls. Mean volumes of the subcortical nuclei did not differ significantly between groups, and mean volume of temporal lobe brain matter decreased significantly more than whole brain, suggesting regional loss of brain matter in DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain matter and temporal lobe volumes and significantly larger volumes of lateral ventricles, and of temporal lobe peripheral CSF, than did controls. Neuropsychological measures of disease severity in DAT patients were significantly (p < 0.05) and appropriately correlated to volumes of cerebral brain matter and right lateral ventricle. These results suggest that in DAT: (i) significant brain atrophy is present early in the disease process, (ii) brain atrophy correlates with severity of cognitive impairment, and (iii) there is greater involvement of the telencephalic association system than whole brain, and there is relative sparing of the caudate, lenticular and thalamic nuclei. RP MURPHY, DGM (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 414,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009; McIntosh, Anthony/G-4955-2011; daly, eileen/B-6716-2011 NR 56 TC 92 Z9 94 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1993 VL 34 IS 9 BP 612 EP 621 DI 10.1016/0006-3223(93)90153-5 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MH048 UT WOS:A1993MH04800005 PM 8292690 ER PT J AU BLAKE, CA CAMPBELL, GT MASCAGNI, F CULLER, MD NEGROVILAR, A AF BLAKE, CA CAMPBELL, GT MASCAGNI, F CULLER, MD NEGROVILAR, A TI EFFECTS OF INJECTION OF ANTI-LUTEINIZING HORMONE (LH)-RELEASING HORMONE SERUM AND ANTI-GONADOTROPIN-RELEASING HORMONE-ASSOCIATED PEPTIDE SERUM INTO NEONATAL RATS ON LH AND FOLLICLE-STIMULATING-HORMONE CELLS SO BIOLOGY OF REPRODUCTION LA English DT Article ID ADULT MALE-RATS; IMMUNOCYTOCHEMICAL LOCALIZATION; ADENOHYPOPHYSEAL CELLS; INHIBITING FACTOR; ESTROUS-CYCLE; FEMALE RATS; SECRETION; PRECURSOR; DIFFERENTIATION; PROHORMONE AB Relatively little is known regarding the potential importance of LHRH and of gonadotropin-releasing hormone-associated peptide (GAP) on the postnatal development of gonadotrophs. We investigated the effects of administration of anti (A)-LHRH serum or A-GAP serum to neonatal rats on the development of LH and FSH immunoreactivity in anterior pituitary gland (APG) cells. Serum (sheep non-immune [NSS], sheep A-LHRH, sheep A-LHRH/GAP [which bound LHRH and GAP], rabbit non-immune [NRS], or rabbit A-GAP) was injected s.c. into neonatal female and male rats on Days 1 and 3 or Days 1, 3, 5, and 7 after birth. Pups were killed on Day 5 or 9, two days after the last injection. The percentages of APG cells immunoreactive for LH or FSH increased from Day 1 to Day 5 and did not change between Days 5 and 9 in female pups treated with NSS or NRS. There was a trend for the percentages of LH and FSH cells to increase from Day 1 to Days 5 and 9 in male pups treated with NSS or NRS, but the increases were not statistically significant. In both females and males, treatment with antisera that recognized LHRH reduced the percentage of FSH cells on Day 5 and the percentages of LH and FSH cells on Day 9. Treatment with A-GAP was without effect in both sexes. There were similar percentages of LH and FSH cells in females and a lower percentage of FSH than of LH cells in males in the Day 5 and 9 controls. In females, administration of antisera that recognized LHRH resulted in a lower percentage of FSH than of LH cells on Days 5 and 9. LH and FSH cell size did not change from Day 1 to Day 5 or 9 in controls of either sex. In females, administration of antisera that recognized LHRH decreased the size of FSH cells an Days 5 and 9, and A-LHRH/GAP decreased the size of LH cells on Day 9. A-GAP had no effect in females, and no treatment had any significant effect on the size of LH or FSH cells in males. LH and FSH cell sizes were not different within any group of either sex. The results indicate that LHRH but not GAP plays a role in the development of the percentage of APG cells with LH or FSH immunoreactivity in the APG of female and male rats and affects the size of gonadotrophs in female rats. The results also suggest that, at least in females, LHRH is important for maintaining FSH synthesis in gonadotrophs. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. RP BLAKE, CA (reprint author), UNIV S CAROLINA,SCH MED,DEPT CELL BIOL & NEUROSCI,COLUMBIA,SC 29208, USA. FU NICHD NIH HHS [NIEHS HD-22687] NR 21 TC 6 Z9 6 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1993 VL 49 IS 5 BP 965 EP 971 DI 10.1095/biolreprod49.5.965 PG 7 WC Reproductive Biology SC Reproductive Biology GA MC961 UT WOS:A1993MC96100010 PM 8286592 ER PT J AU OBRIEN, DA GABEL, CA EDDY, EM AF OBRIEN, DA GABEL, CA EDDY, EM TI MOUSE SERTOLI CELLS SECRETE MANNOSE 6-PHOSPHATE CONTAINING GLYCOPROTEINS THAT ARE ENDOCYTOSED BY SPERMATOGENIC CELLS SO BIOLOGY OF REPRODUCTION LA English DT Article ID GROWTH FACTOR-II; MESSENGER RIBONUCLEIC-ACID; LYSOSOMAL-ENZYMES; PACHYTENE SPERMATOCYTES; HORMONAL-REGULATION; PHOSPHORYLATED OLIGOSACCHARIDES; FACTOR-BETA-1 PRECURSOR; BETA-GLUCURONIDASE; INHIBIN PRODUCTION; MOLECULAR-CLONING AB Sertoli cells were isolated from prepubertal mice and cultured in serum-free medium to determine whether they secrete glycoproteins containing mannose 6-phosphate (M6P). Assays of the conditioned medium for lysosomal enzyme precursors, which typically bear the M6P recognition marker, indicated that Sertoli cells selectively secreted beta-N-acetylhexosaminidase and alpha-mannosidase, but not beta-glucuronidase or beta-galactosidase. Sertoli cells were labeled metabolically with [S-35]methionine and the conditioned medium was fractionated on a cation-independent M6P receptor affinity column. Most of the secreted proteins did not bind to the column (peak A); however, approximately 10% of the radioactivity eluted as a low-affinity fraction (peak B), and 5-11% of the recovered cpm bound to the column and were eluted with 2.5 mM M6P (peak C). The radiolabeled proteins in each fraction were analyzed by one- and two-dimensional electrophoresis and fluorography. Two protein bands with molecular weights of 30 000 and 35 000 were present in peak B. Peak C contained at least ten M6P-containing glycoproteins with molecular weights between 30 000 and 135 000 and isoelectric points < 6.5. The 35 000-molecular-weight constituent prominent both in peaks B and C was identified as procathepsin L by immunoprecipitation with a specific antibody. When pachytene spermatocytes and round spermatids were cultured overnight in the presence of peak C glycoproteins radiolabeled with I-125, both germ cell types accumulated these Sertoli M6P-glycoproteins by a receptor-mediated process that was specifically inhibited by M6P. The Sertoli M6P-glycoproteins taken up by germ cells were processed to lower molecular weight forms. These results provide evidence that M6P receptors on the surface of spermatogenic cells endocytose secrete glycoproteins that are likely to be present in the seminiferous epithelium. C1 UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. NIEHS,GAMETE BIOL SECT,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. PFIZER INC,DEPT IMMUNOL & INFECT DIS,DIV CENT RES,GROTON,CT 06340. RP OBRIEN, DA (reprint author), UNIV N CAROLINA,REPROD BIOL LABS,CB 7500,MACNIDER BLDG,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA16086]; NICHD NIH HHS [P30-HD18968, HD26485, R01 HD026485] NR 66 TC 28 Z9 28 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1993 VL 49 IS 5 BP 1055 EP 1065 DI 10.1095/biolreprod49.5.1055 PG 11 WC Reproductive Biology SC Reproductive Biology GA MC961 UT WOS:A1993MC96100021 PM 8286571 ER PT J AU SANDBERG, K BOR, M JI, H CARVALLO, PM CATT, KJ AF SANDBERG, K BOR, M JI, H CARVALLO, PM CATT, KJ TI ATRIAL-NATRIURETIC-FACTOR ACTIVATES CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE PHOSPHODIESTERASE IN XENOPUS-LAEVIS OOCYTES AND POTENTIATES PROGESTERONE-INDUCED MATURATION VIA CYCLIC GUANOSINE 5'-MONOPHOSPHATE ACCUMULATION SO BIOLOGY OF REPRODUCTION LA English DT Article ID DEPENDENT PROTEIN-KINASE; GROWTH FACTOR-I; NUCLEOTIDE PHOSPHODIESTERASES; TESTOSTERONE PRODUCTION; AMP PHOSPHODIESTERASE; GUANYLATE-CYCLASE; ENDOTHELIAL-CELLS; SMOOTH-MUSCLE; PEPTIDE; CGMP AB Xenopus oocytes were found to express atrial natriuretic factor (ANF) receptors that activate guanylate cyclase and stimulate cyclic guanosine 5'-monophosphate (cGMP) production in a dose- and time-dependent manner. A truncated fragment of ANF, known to bind to mammalian ANF receptors without stimulating cGMP accumulation, did not elicit a cGMP response in oocytes. In addition, preincubation with ANF increased the number of oocytes that underwent progesterone-induced maturation. The maximally effective dose of ANF (1 muM) elevated intracellular and extracellular cGMP accumulation from 50 to 200 and 5 to 800 fmol/oocyte, respectively, and increased the number of maturing oocytes by up to 3-fold. ANF's effects on progesterone-induced maturation were mimicked by nonhydrolyzable analogues of cGMP. ANF and 8-Br-cGMP had no effect on maturation in the absence of progesterone, indicating that elevation of cGMP alone is not sufficient to induce maturation. Dibutyryl-cGMP was as effective as 8-Br-cGMP, whereas 8-Br-guanosine monophosphate, 8-Br-guanosine, and 8-Br-cyclic inosine monophosphate did not potentiate ovum maturation. In Xenopus oocytes, an initial step in progesterone-induced maturation is the reduction of intracellular cAMP levels; both ANF and 8-Br-cGMP lowered cAMP levels and enhanced progesterone's ability to do so. This decrease in cAMP levels was attributable to increased cAMP-phosphodiesterase activity, which was enhanced by both ANF and 8-Br-cGMP. These findings, and the presence of functional ANF receptors on Xenopus oocytes, demonstrate that ANF can participate in ovum development by stimulation of cGMP accumulation and activation of cAMP phosphodiesterase, thereby potentiating progesterone's ability to decrease cAMP levels and promote ovum maturation. C1 UNIV CHILE,FAC MED,DEPT BIOQUIM,SANTIAGO 7,CHILE. RP SANDBERG, K (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,RM 6A-36,BETHESDA,MD 20892, USA. NR 50 TC 14 Z9 16 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1993 VL 49 IS 5 BP 1074 EP 1082 DI 10.1095/biolreprod49.5.1074 PG 9 WC Reproductive Biology SC Reproductive Biology GA MC961 UT WOS:A1993MC96100023 PM 8286573 ER PT J AU ALKON, DL ETCHEBERRIGARAY, R ROJAS, E AF ALKON, DL ETCHEBERRIGARAY, R ROJAS, E TI DISTRIBUTION OF VOLTAGE SENSORS IN MAMMALIAN OUTER HAIR-CELLS SO BIOPHYSICAL JOURNAL LA English DT Editorial Material ID CHARGE MOVEMENT; MECHANISM C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20852. RP ALKON, DL (reprint author), NINCDS,ADAPT SYST LAB,BETHESDA,MD 20852, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1993 VL 65 IS 5 BP 1755 EP 1756 PG 2 WC Biophysics SC Biophysics GA MF321 UT WOS:A1993MF32100006 PM 8298008 ER PT J AU VODYANOY, I BEZRUKOV, SM PARSEGIAN, VA AF VODYANOY, I BEZRUKOV, SM PARSEGIAN, VA TI PROBING ALAMETHICIN CHANNELS WITH WATER-SOLUBLE POLYMERS - SIZE-MODULATED OSMOTIC ACTION SO BIOPHYSICAL JOURNAL LA English DT Article ID BILAYER-MEMBRANES; VOLUME CHANGES; ION CHANNEL; VOLTAGE; CONDUCTANCE; ACTIVATION AB Contrary to expectations based on heightened solution viscosity, alamethicin channels appear to speed up in the presence of water soluble polyethylene glycols (PEGs) and dextrans. Specifically, added polymers reduce the probabilities of transition to higher-conductance states but do not change channel lifetimes They thereby shorten the duration of current ''bursts.'' These modified probabilities and kinetics reveal the action of polymer osmotic stress to suppress channel formation. The osmotic action of large, fully excluded polymers shows that some 3,000 angstrom3 of water are taken up by the channel from the solution upon each transition to an adjacent higher-conductance state. The partial osmotic action of incompletely excluded polymers reveals the extent of exclusion for different-size polymers. The partial exclusion thus measured agrees remarkably well with estimates using data on reduction of single-channel conductance by current-impeding polymers. One can relate the degree of each polymer's exclusion to its size and to the radius of the channel pore. C1 NIDDKD,DIV INTRAMURAL RES,BLDG 5,ROOM 405,BETHESDA,MD 20892. OFF NAVAL RES,ARLINGTON,VA 22217. ST PETERSBURG NUCL PHYS INST,ST PETERSBURG 188350,RUSSIA. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 21 TC 57 Z9 58 U1 0 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1993 VL 65 IS 5 BP 2097 EP 2105 PG 9 WC Biophysics SC Biophysics GA MF321 UT WOS:A1993MF32100041 PM 7507718 ER PT J AU KUTTY, RK KUTTY, G DUNCAN, T NICKERSON, J CHADER, GJ WIGGERT, B AF KUTTY, RK KUTTY, G DUNCAN, T NICKERSON, J CHADER, GJ WIGGERT, B TI RADIOANALYTIC ESTIMATION OF AMPLIFICATION PRODUCTS GENERATED BY REVERSE TRANSCRIPTION PCR USING [ALPHA-P-33] DEOXYRIBONUCLEOSIDE TRIPHOSPHATE SO BIOTECHNIQUES LA English DT Note ID POLYMERASE CHAIN-REACTION C1 EMORY UNIV,ATLANTA,GA 30322. RP KUTTY, RK (reprint author), NEI,LRCMB,ROOM 338,BLDG 6,BETHESDA,MD 20892, USA. NR 4 TC 5 Z9 5 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 NOV PY 1993 VL 15 IS 5 BP 808 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF887 UT WOS:A1993MF88700008 PM 7505598 ER PT J AU SHACTER, E ARZADON, GK WILLIAMS, JA AF SHACTER, E ARZADON, GK WILLIAMS, JA TI STIMULATION OF INTERLEUKIN-6 AND PROSTAGLANDIN-E2 SECRETION FROM PERITONEAL-MACROPHAGES BY POLYMERS OF ALBUMIN SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; BOVINE SERUM-ALBUMIN; HEPATITIS-B VIRUS; ENDOTHELIAL-CELLS; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; GROWTH-FACTOR; IL-6; MONOCYTES; PROTEINS RP SHACTER, E (reprint author), NCI,IST GENET,BLDG 37,ROOM 2B-03,BETHESDA,MD 20892, USA. NR 73 TC 18 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1993 VL 82 IS 9 BP 2853 EP 2864 PG 12 WC Hematology SC Hematology GA ME657 UT WOS:A1993ME65700031 PM 8219233 ER PT J AU FREEDMAN, LS MACHIN, D AF FREEDMAN, LS MACHIN, D TI PATHOLOGY REVIEW IN CANCER-RESEARCH SO BRITISH JOURNAL OF CANCER LA English DT Editorial Material ID REPRODUCIBILITY; CARCINOMA; LYMPHOMAS C1 MRC,CANC TRIALS OFF,CAMBRIDGE CB2 2BB,ENGLAND. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,ROOM 344,BETHESDA,MD 20892, USA. NR 21 TC 4 Z9 4 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 NOV PY 1993 VL 68 IS 5 BP 827 EP 830 DI 10.1038/bjc.1993.440 PG 4 WC Oncology SC Oncology GA MD800 UT WOS:A1993MD80000001 PM 8217596 ER PT J AU DANESI, R DELBIANCHI, S SOLDANI, P CAMPAGNI, A LAROCCA, RV MYERS, CE PAPARELLI, A DELTACCA, M AF DANESI, R DELBIANCHI, S SOLDANI, P CAMPAGNI, A LAROCCA, RV MYERS, CE PAPARELLI, A DELTACCA, M TI SURAMIN INHIBITS BFGF-INDUCED ENDOTHELIAL-CELL PROLIFERATION AND ANGIOGENESIS IN THE CHICK CHORIOALLANTOIC MEMBRANE SO BRITISH JOURNAL OF CANCER LA English DT Article ID FIBROBLAST GROWTH-FACTOR; PROSTATE-CANCER; FACTOR RECEPTOR; TUMOR-GROWTH; PROTEIN; HEPARIN; ASSAY; TRANSFORMATION; EXPRESSION; ANTISENSE AB The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [H-3]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 mug ml-1. bFGF antisense oligomer (10 mum) reduced [H-3]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 mug was a more potent inhibitor of angiogenesis than the combination of heparin 60 mug/hydrocortisone 50 mug; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (-35 and -29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone. C1 UNIV PISA,IST FARM MED,VIA ROMA 55,I-56126 PISA,ITALY. UNIV PISA,SCUOLA SUPER,I-56127 PISA,ITALY. UNIV PISA,INST ANAT UMANA NORMALE,I-56126 PISA,ITALY. PERFEZIONAMENTO S ANNA,I-56127 PISA,ITALY. CTR RICERCHE ESPERIENZE APPL MIL,I-56100 PISA,ITALY. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. OI SOLDANI, PAOLA/0000-0003-1703-0962 NR 40 TC 77 Z9 78 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV PY 1993 VL 68 IS 5 BP 932 EP 938 DI 10.1038/bjc.1993.457 PG 7 WC Oncology SC Oncology GA MD800 UT WOS:A1993MD80000018 PM 7692920 ER PT J AU ZHENG, W JIN, F DEVESA, SS BLOT, WJ FRAUMENI, JF GAO, YT AF ZHENG, W JIN, F DEVESA, SS BLOT, WJ FRAUMENI, JF GAO, YT TI DECLINING INCIDENCE IS GREATER FOR ESOPHAGEAL THAN GASTRIC-CANCER IN SHANGHAI, PEOPLES-REPUBLIC-OF-CHINA SO BRITISH JOURNAL OF CANCER LA English DT Article ID STOMACH-CANCER; RISK-FACTORS; DIET; EPIDEMIOLOGY; MORTALITY; CONSUMPTION; LINXIAN; TRENDS; CARDIA; FRUIT AB Temporal trends in the incidence of esophageal and gastric cancers during 1972 to 198 were addressed in urban Shanghai, the location of China's longest standing cancer registry. Over the 18 year study period, esophageal cancer rates decreased more than 50% from 28.8/100,000 person-years in 1972-74 to 13.3/100,000 in 1987-89 among men and from 11.3/100,000 to 5.4/100,000 among women. Reductions were apparent in each age group, but most pronounced among younger generations, with more than a 75% decline in incidence among those under age 55 years. The incidence rate for stomach cancer among men decreased 20% from 62.0/100,000 in 1972-74 to 50.1/100,000 in 1987-89. The reduction among women, however, was minor, from 23.9/100,000 to 23.2/100,000. The patterns varied by age, with declines among persons 45-64 years and increases among those in older and younger age groups. The determinants of these trends are not clear, but appear related in part to dietary changes. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI 200032,PEOPLES R CHINA. NR 33 TC 18 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV PY 1993 VL 68 IS 5 BP 978 EP 982 DI 10.1038/bjc.1993.465 PG 5 WC Oncology SC Oncology GA MD800 UT WOS:A1993MD80000026 PM 8217613 ER PT J AU JANIK, JE SZNOL, M URBA, WJ FIGLIN, R BUKOWSKI, RM FYFE, G PIERCE, WC BELLDEGRUN, A SHARFMAN, WH SMITH, JW LONGO, DL AF JANIK, JE SZNOL, M URBA, WJ FIGLIN, R BUKOWSKI, RM FYFE, G PIERCE, WC BELLDEGRUN, A SHARFMAN, WH SMITH, JW LONGO, DL TI ERYTHROPOIETIN PRODUCTION - A POTENTIAL MARKER FOR INTERLEUKIN-2 INTERFERON-RESPONSIVE TUMORS SO CANCER LA English DT Article DE ERYTHROPOIETIN; IMMUNOTHERAPY; INTERLEUKIN-2; ALPHA-INTERFERON; RENAL CELL CANCER; TUMOR MARKER; TUMOR ANTIGEN ID RENAL-CELL CARCINOMA; RECOMBINANT INTERLEUKIN-2; LYMPHOCYTES-T; IMMUNOTHERAPY; MELANOMA; CANCER; GENE AB Background. Interleukin-2 (IL-2) recently was approved by the Food and Drug Administration for the treatment of renal cell cancer. It is effective in a small minority of patients, but no markers identify individuals likely to respond to treatment. Methods. Two polycythemic patients with erythropoietin-producing renal cell cancer and three other polycythemic patients with renal cell cancer were treated with the combination of IL-2 and alpha-interferon (alpha-IFN). Results. All five patients achieved a partial or complete remission. In both patients in which it was measured, the erythropoietin level decreased significantly with treatment, and the polycythemia resolved in all patients. Hypothyroidism developed in two patients, and transient hyperthyroidism developed in another. Conclusion. These results contrast with those achieved with IL-2 alone or in combination with lymphokine-activated killer cells, for which a 15% response rate was seen in patients with renal cell cancer and polycythemia. Although less than 5% of renal cell tumors produce erythropoietin, its production may identify a subset of individuals with renal cell cancer responsive to IL-2 and alpha-IFN. C1 NCI, FCRDC, PROGRAM RESOURCES INC, DYNCORP, FREDERICK, MD 21701 USA. NCI, DIV CANC TREATMENT, CANC THERAPY EVALUAT PROGRAM, INVEST DRUG BRANCH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, DEPT MED, DIV HEMATOL ONCOL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, DEPT SURG, DIV UROL, LOS ANGELES, CA USA. CETUS ONCOL DIV, EMERYVILLE, CA USA. CLEVELAND CLIN, CLEVELAND, OH 44106 USA. RP JANIK, JE (reprint author), NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21701 USA. FU NCI NIH HHS [N01-CO-74102] NR 16 TC 24 Z9 24 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 1993 VL 72 IS 9 BP 2656 EP 2659 DI 10.1002/1097-0142(19931101)72:9<2656::AID-CNCR2820720922>3.0.CO;2-A PG 4 WC Oncology SC Oncology GA MD113 UT WOS:A1993MD11300020 PM 8402486 ER PT J AU WILKS, RJ LAGRENADE, L HANCHARD, B CAMPBELL, M MURPHY, J CRANSTON, B BLATTNER, WA MANNS, A AF WILKS, RJ LAGRENADE, L HANCHARD, B CAMPBELL, M MURPHY, J CRANSTON, B BLATTNER, WA MANNS, A TI SIBLING ADULT T-CELL LEUKEMIA-LYMPHOMA AND CLUSTERING OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I INFECTION IN A JAMAICAN FAMILY SO CANCER LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 INFECTION; ADULT T-CELL LEUKEMIA LYMPHOMA; FAMILY STUDIES ID HTLV-I; CHILD TRANSMISSION; RETROVIRUS; PATIENT; MEMBERS AB Background. Human T-cell lymphotropic virus type I (HTLV-I) infection is endemic in jamaica, with an estimated crude seroprevalence of 5%. Adult T-cell lymphoma/leukemia (ATL), a disease caused hy HTLV-I, has an incidence of 1-2/100,000 in the Jamaican population. Familial ATL has not previously been reported from Jamaica. Methods. Hospital records and histologic specimens of the two cases were reviewed. HTLV-I infection was confirmed by antibody testing and by polymerase chain reaction on paraffin-embedded tissue, where serum was unavailable. Family members were identified by the patients' parents. After giving informed consent, family members were asked to complete an interviewer-administered questionnaire and to agree to phlebotomy. Results. ATL developed 10 years apart in two siblings from a Jamaican family at age 16 and 24 years. A study of 19 members of their extended family, including both parents, 2 grandparents, and 3 siblings, revealed an overall HTLV-I seroprevalence of 17%. This compared with 75% among parents and siblings living in the same household as the patients. HTLV-I antibody-positive (HTLV-I-positive) and negative family members had similar mean age. Three of 3 HTLV-I-positive subjects were breast-fed, compared with 10 of 15 HTLV-I-negative subjects. Intravenous drug abuse, sex with prostitutes, homosexuality, and blood transfusion were not reported. The mean number of sexual partners were similar. Both parents, who were antibody-positive, had polylobated atypical lymphocytes in their peripheral blood. Conclusion. The HTLV-I antibody seroprevalence is greater in the family than in the general population, consistent with the modes of transmission. The antibody seronegativity of both grandmothers suggests sexual transmission between parents. The development of ATL at age 16 and 24 years is consistent with maternal-infant transmission and a long latent period, as reported by other authors. C1 UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. NCI,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RP WILKS, RJ (reprint author), UNIV W INDIES,DEPT MED,TROP METAB RES UNIT,KINGSTON 7,JAMAICA. FU NCI NIH HHS [N01-CP-31006] NR 23 TC 13 Z9 14 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1993 VL 72 IS 9 BP 2700 EP 2704 DI 10.1002/1097-0142(19931101)72:9<2700::AID-CNCR2820720929>3.0.CO;2-9 PG 5 WC Oncology SC Oncology GA MD113 UT WOS:A1993MD11300027 PM 8402493 ER PT J AU HAHN, SM LIEBMANN, JE COOK, J FISHER, J GOLDSPIEL, B VENZON, D MITCHELL, JB KAUFMAN, D AF HAHN, SM LIEBMANN, JE COOK, J FISHER, J GOLDSPIEL, B VENZON, D MITCHELL, JB KAUFMAN, D TI TAXOL IN COMBINATION WITH DOXORUBICIN OR ETOPOSIDE - POSSIBLE ANTAGONISM IN-VITRO SO CANCER LA English DT Article DE TAXOL; ETOPOSIDE; DOXORUBICIN; ANTAGONISM; CELL CULTURE ID PHASE-I TRIAL; INFUSION; TUBULIN; AGENT; CELLS AB Background. Taxol is a novel chemotherapeutic agent that promotes microtubule assembly and stabilizes tubulin polymer formation. Clinical evaluation of its anti-neoplastic activity as a single agent and in combination with other chemotherapeutic drugs is in progress. Methods. To evaluate the effect of combining taxol with other commonly used antineoplastic agents, clonogenic survival of human breast cancer MCF7 cells, human lung adenocarcinoma A549 cells, and human ovarian cancer OVG1 cells were assayed after an initial exposure to taxol for 24 hours (approximately LD90 for taxol), followed by a 1-hour incubation with varying concentrations of doxorubicin or etoposide (total taxol incubation time, 25 hours). Results. When corrected for taxol-induced cytotoxicity, doxorubicin and etoposide caused less cell killing in the presence of taxol compared with control incubations of doxorubicin and etoposide alone. To determine if a different schedule of drug application resulted in a similar finding, MCF7, A549, and OVG1 cells were exposed to doxorubicin for 1 hour, followed by incubation with varying concentrations of taxol for 24 hours. Less-than-additive cytotoxicity for the combination of taxol and doxorubicin was found. Flow cytometry studies in MCF7 cells showed that taxol caused a G2/M cell cycle block. Fewer cells were found to be in S-phase, which is the most doxorubicin-sensitive phase of the cell cycle. The application of doxorubicin or etoposide to MCF7 cells for 1 hour resulted in partial G1 and G2/M cell cycle blocks. Fewer cells were found to be moving through the cell cycle, which is likely required for taxol cytotoxicity. Conclusion. Although direct antagonism of the cytotoxicity of doxorubicin or etoposide by taxol has not been proven. there is less-than-additive in vitro cytotoxicity when taxol is combined with these chemotherapeutic agents. The clinical implications of these findings are unknown; however, these findings generate concern about the combination of these agents in clinical trials and suggest that additional studies to determine optimal scheduling are needed. C1 NCI,CTR CLIN,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP HAHN, SM (reprint author), NCI,RADIAT ONCOL BRANCH,CLIN ONCOL PROGRAM,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 18 TC 77 Z9 77 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1993 VL 72 IS 9 BP 2705 EP 2711 DI 10.1002/1097-0142(19931101)72:9<2705::AID-CNCR2820720930>3.0.CO;2-K PG 7 WC Oncology SC Oncology GA MD113 UT WOS:A1993MD11300028 PM 8104682 ER PT J AU KAUFMAN, D AF KAUFMAN, D TI CANCER-THERAPY AND THE RANDOMIZED CLINICAL-TRIAL - GOOD MEDICINE SO CANCER LA English DT Article; Proceedings Paper CT INTERACTIVE WORKSHOP ON MEDICAL ETHICS VERSUS MEDICAL ECONOMICS : A HEALTH CARE DILEMMA IN CANCER PATIENT CARE CY FEB 16-17, 1993 CL WASHINGTON, DC SP AMER CANC SOC, ROCHE LABS DE CANCER; ETHICS; CLINICAL TRIALS; RISK MANAGEMENT ID HODGKINS-DISEASE; MOPP; CARE AB True improvements in the treatment of cancer-by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities-result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine. RP KAUFMAN, D (reprint author), NCI,DIV CANC TREATMENT,BLDG 31,ROOM 3A44,BETHESDA,MD 20892, USA. NR 13 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1993 VL 72 IS 9 SU S BP 2801 EP 2804 DI 10.1002/1097-0142(19931101)72:9+<2801::AID-CNCR2820721505>3.0.CO;2-N PG 4 WC Oncology SC Oncology GA MD661 UT WOS:A1993MD66100003 PM 8402507 ER PT J AU CANTOR, KP LYNCH, CF JOHNSON, D AF CANTOR, KP LYNCH, CF JOHNSON, D TI REPRODUCTIVE FACTORS AND RISK OF BRAIN, COLON, AND OTHER MALIGNANCIES IN IOWA (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE BRAIN CANCER; COLON CANCER; HORMONES; KIDNEY CANCER; PANCREAS CANCER; PARITY; RECTAL CANCER; REPRODUCTIVE FACTORS; UNITED-STATES AB The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 population-based controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI] = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer. RP CANTOR, KP (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. FU NCI NIH HHS [NCI NO1-CP-85614, NCI-NO1-CP-51026, 5 KO7 CA01181-05] NR 0 TC 68 Z9 69 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 NOV PY 1993 VL 4 IS 6 BP 505 EP 511 DI 10.1007/BF00052425 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA MJ062 UT WOS:A1993MJ06200001 PM 8280827 ER PT J AU STRICKLAND, PT ROUTLEDGE, MN DIPPLE, A AF STRICKLAND, PT ROUTLEDGE, MN DIPPLE, A TI METHODOLOGIES FOR MEASURING CARCINOGEN ADDUCTS IN HUMANS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID WHITE BLOOD-CELLS; HYDROCARBON-DNA ADDUCTS; POLYCYCLIC AROMATIC-HYDROCARBONS; CHROMATOGRAPHY MASS-SPECTROMETRY; P-32 POSTLABELING ASSAY; ELECTRON-CAPTURE DETECTION; ALKYLATED AMINO-ACIDS; IRON FOUNDRY WORKERS; GAS-CHROMATOGRAPHY; HEMOGLOBIN ADDUCTS C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. RP STRICKLAND, PT (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [N01-CO-74101]; NIEHS NIH HHS [ES06052, ES03819] NR 137 TC 25 Z9 25 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 NOV-DEC PY 1993 VL 2 IS 6 BP 607 EP 619 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA MG331 UT WOS:A1993MG33100017 PM 8268781 ER PT J AU RISINGER, JI BERCHUCK, A KOHLER, MF WATSON, P LYNCH, HT BOYD, J AF RISINGER, JI BERCHUCK, A KOHLER, MF WATSON, P LYNCH, HT BOYD, J TI GENETIC INSTABILITY OF MICROSATELLITES IN ENDOMETRIAL CARCINOMA SO CANCER RESEARCH LA English DT Note ID LYNCH SYNDROME-II; COLORECTAL-CANCER; KINDREDS; FAMILY; IDENTIFICATION; POLYPOSIS; DIAGNOSIS; PMCT118; DNA AB Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts, notably the endometrium. A genetic locus for HPNCC was recently determined by linkage analysis to exist on chromosome 2p; both sporadic and HNPCC-associated colorectal carcinomas exhibit a ''replication error'' phenotype, characterized by instability of dinucleotide repeat sequences throughout the genome. Here, we address the hypothesis that the replication error phenotype would be evident in some fraction of sporadic endometrial carcinomas or in those associated with HNPCC. Microsatellite instability was observed in 17% of sporadic endometrial carcinomas and in 75% of those tumors associated with HNPCC. These data indicate that the HNPCC gene is also involved in heritable and somatic forms of endometrial carcinoma. C1 NIEHS,MOLEC CARCINOGENESIS LAB,GYNECOL PATHOBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. NR 27 TC 528 Z9 531 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1993 VL 53 IS 21 BP 5100 EP 5103 PG 4 WC Oncology SC Oncology GA MD950 UT WOS:A1993MD95000010 PM 8221644 ER PT J AU SHAW, GL GAZDAR, AF PHELPS, R LINNOILA, RI IHDE, DC JOHNSON, BE OIE, HK PASS, HI STEINBERG, SM GHOSH, BC WALSH, TE NESBITT, JC COTELINGAM, JD MINNA, JD MULSHINE, JL AF SHAW, GL GAZDAR, AF PHELPS, R LINNOILA, RI IHDE, DC JOHNSON, BE OIE, HK PASS, HI STEINBERG, SM GHOSH, BC WALSH, TE NESBITT, JC COTELINGAM, JD MINNA, JD MULSHINE, JL TI INDIVIDUALIZED CHEMOTHERAPY FOR PATIENTS WITH NONSMALL CELL LUNG-CANCER DETERMINED BY PROSPECTIVE IDENTIFICATION OF NEUROENDOCRINE MARKERS AND IN-VITRO DRUG-SENSITIVITY TESTING SO CANCER RESEARCH LA English DT Article ID NEURO-ENDOCRINE DIFFERENTIATION; L-DOPA DECARBOXYLASE; COMBINATION CHEMOTHERAPY; BRONCHOGENIC CARCINOMA; RANDOMIZED TRIAL; GENE-MUTATIONS; HUMAN-TUMORS; LINES; EXPRESSION; SURVIVAL AB We attempted to prospectively select individualized chemotherapy for 165 non-small cell lung cancer patients based on in vitro analysis of neuroendocrine (NE) markers and drug sensitivity testing (DST) using fresh tumor. The chemotherapy used for small cell lung cancer (SCLC) was selected when NE marker expression determined by L-dopa decarboxylase assay was documented. Selection of chemotherapy for other patients was guided by DST results using a modified dye exclusion assay when available; otherwise etoposide and cisplatin was administered. A total of 112 of 165 (68%) specimens were assayed for L-dopa decarboxylase and 36 patients (22%) had DST. In vitro data directed management for 27 of 96 (28%) patients given chemotherapy: 6 with NE markers were treated with the SCLC regimen; and 21 (58% of those with DST) received their DST-selected chemotherapy regimen. There were no significant differences in response rate among all 3 treatment arms (P = 0.076). However, response to chemotherapy for the patients treated prospectively with a SCLC regimen was 3 of 6 (50%), marginally better than patients given their DST-selected chemotherapy regimen (2 of 21; 9 %; P = 0.056) or those treated with etoposide and cisplatin (10 of 69; 14%; P = 0.061). When patients whose NE markers were identified retrospectively are included, 4 of 9 (44%) responded to administered chemotherapy, compared to 7 of 55 (13%) with no NE markers present (P = 0.04). There were no differences in survival among the three treatment groups. Cisplatin and etoposide comprised the most active regimen in vitro for tumors from 16 of 36 (44%) patients, potentially limiting the benefit of DST since this is often the empiric therapy for non-SCLC. Furthermore, the correlation between in vitro and clinical response is nonsignificant for all drugs tested, highlighting the overall relative resistance of non-SCLC tumors to currently available chemotherapy. C1 NCI, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20817 USA. NR 45 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1993 VL 53 IS 21 BP 5181 EP 5187 PG 7 WC Oncology SC Oncology GA MD950 UT WOS:A1993MD95000023 PM 8221655 ER PT J AU MOODY, TW FAGARASAN, M ZIA, F CESNJAJ, M GOLDSTEIN, AL AF MOODY, TW FAGARASAN, M ZIA, F CESNJAJ, M GOLDSTEIN, AL TI THYMOSIN ALPHA-1 DOWN-REGULATES THE GROWTH OF HUMAN NONSMALL CELL LUNG-CANCER CELLS IN-VITRO AND IN-VIVO SO CANCER RESEARCH LA English DT Article ID VASOACTIVE INTESTINAL POLYPEPTIDE; HIGH-AFFINITY; LINES; PEPTIDE; ADENOCARCINOMA; EXPRESSION; SECRETION; RECEPTORS; CARCINOMA; ONCOGENE AB The effect of thymosin alpha1 (THNalpha1) and it, NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THNalpha1 antibody, receptors we identified on NSCLC cells that were pretreated with 10(-6) M THNalpha1. [H-3]Arachidonic acid was readily taken up by NSCLC cells and THNalpha1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THNbeta4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THNalpha1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THNbeta4 were less potent. Using growth assays in vivo, THNalpha1 (10 mug s.c./day) but not THN1-14, THN15-28, or THNbeta4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THNalpha1 receptors are present on NSCLC cells and that native THNalpha1 inhibits the growth of human NSCLC. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. NICHHD,ENDOCRINOL LAB,BETHESDA,MD 20892. NICHHD,REPROD RES BRANCH,BETHESDA,MD 20892. NR 30 TC 30 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1993 VL 53 IS 21 BP 5214 EP 5218 PG 5 WC Oncology SC Oncology GA MD950 UT WOS:A1993MD95000028 PM 8221658 ER PT J AU FREEMAN, SM ABBOUD, CN WHARTENBY, KA PACKMAN, CH KOEPLIN, DS MOOLTEN, FL ABRAHAM, GN AF FREEMAN, SM ABBOUD, CN WHARTENBY, KA PACKMAN, CH KOEPLIN, DS MOOLTEN, FL ABRAHAM, GN TI THE BYSTANDER EFFECT - TUMOR-REGRESSION WHEN A FRACTION OF THE TUMOR MASS IS GENETICALLY-MODIFIED SO CANCER RESEARCH LA English DT Article ID THYMIDINE KINASE GENES; RETROVIRAL VECTORS; BRAIN-TUMORS; RENAL-CANCER; CELLS; INVIVO; APOPTOSIS; INTERLEUKIN-4; LYMPHOCYTES; EXPRESSION AB Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV). We demonstrate here that HSV-TK-positive cells exposed to GCV were lethal to HSV-TK-negative cells as a result of a ''bystander effect.'' HSV-TK-negative cells were killed in vitro when the population of cultured cells contained only 10% HSV-TK-positive cells. The mechanism of this ''bystander effect'' on HSV-TK-negative cells appeared to be related to the process of apoptotic cell death when HSV-TK-positive cells were exposed to GCV. Flow cytometric and electron microscopic analyses suggested that apoptotic vesicles generated from the dying gene-modified cells were phagocytized by nearby, unmodified tumor cells. Prevention of apoptotic vesicle transfer prevented the bystander effect. The toxic effect of HSV-TK-positive cells on HSV-TK-negative cells was reproduced in an in vivo model. A mixed population of tumor cells consisting of HSV-TK-positive and HSV-TK-negative cells was inoculated s.c. into mice. Regression of the tumor mass occurred when the inoculum consisted of as few as 10% HSV-TK-expressing tumor cells. The bystander effect was also demonstrated in i.p. tumor studies. Initial experiments demonstrated that prolonged survival (>70 days) occurred when a mixture containing 50% HSV-TK-positive and 50% HSV-TK-negative cells was injected i.p. followed by GCV treatment. Further, survival was prolonged for mice with a preexisting HSV-TK-negative i.p. tumor burden by injecting HSV-TK-positive cells and GCV. These results suggest that genetic modification of tumor cells may be useful for developing cancer therapies. C1 UNIV ROCHESTER,SCH MED,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,DEPT MED,CLIN IMMUNOL UNIT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,DEPT MED,HEMATOL UNIT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,CTR CANC,ROCHESTER,NY 14642. TULANE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. NCI,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA 01730. FU NCI NIH HHS [CA-53352, P01 CA-59311]; NHLBI NIH HHS [HL-18208] NR 45 TC 996 Z9 1030 U1 6 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1993 VL 53 IS 21 BP 5274 EP 5283 PG 10 WC Oncology SC Oncology GA MD950 UT WOS:A1993MD95000037 PM 8221662 ER PT J AU GREENTREE, WF MILLER, J BUCK, WB AF GREENTREE, WF MILLER, J BUCK, WB TI DIAGNOSIS AND MANAGEMENT OF ACUTE IRON TOXICOSIS SO CANINE PRACTICE LA English DT Article AB Iron poisoning is a potentially serious toxicologic problem in dogs. Its primary impact is on the circulatory and gastrointestinal systems. By evaluating the exposure dosage, clinical symptoms, and serum iron concentrations, an appropriate decision can be made whether to initiate chelation therapy with deferoxamine. Restoring and maintaining fluid, electrolyte, and acid-base balance is essential. Early recognition and prompt initiation of treatment are necessary to decrease the mortality and morbidity associated with dogs who have ingested significant quantities of iron containing products. RP GREENTREE, WF (reprint author), NIH,OCULAR THERAPEUT LAB,BLDG 10,ROOM 10B13,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU VETERINARY PRACTICE PUBL CO PI SANTA BARBARA PA 7 ASHLEY AVE SOUTH, SANTA BARBARA, CA 93103-9989 SN 0094-4904 J9 CANINE PRACT JI Canine Pract. PD NOV-DEC PY 1993 VL 18 IS 6 BP 20 EP 23 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA MJ103 UT WOS:A1993MJ10300004 ER PT J AU GHOSHAL, A SNYDERWINE, EG AF GHOSHAL, A SNYDERWINE, EG TI EXCRETION OF FOOD-DERIVED HETEROCYCLIC AMINE CARCINOGENS INTO BREAST-MILK OF LACTATING RATS AND FORMATION OF DNA-ADDUCTS IN THE NEWBORN SO CARCINOGENESIS LA English DT Note ID COOKED FOOD; METABOLIC-ACTIVATION; DRUG EXCRETION; BINDING; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; MUTAGENICITY; CONSEQUENCES; LIVER; PHIP; MICE AB The distribution, DNA adduction and excretion into breast milk of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were examined in lactating female F344 rats with 5 day old pups. Six hours after a single dose (10 mg/kg, p.o.) of radiolabeled IQ, MeIQx or PhIP to lactating dams, radioactivity in the dams was highest in the liver and kidney followed, in descending order, by the mammary gland, omental fat and brain. By 24 h after carcinogen administration, all tissues of the dams showed significantly reduced levels of radioactivity except for omental fat which changed only marginally from 6 to 24 h. P-32-Postlabeling analysis showed that the level of DNA adducts in mammary gland 6 h after dosing was 2.2, 0.7 and 0.2 adducts/107 nucleotides for PhIP, IQ and MeIQx respectively. In contrast, in hepatic DNA, the levels of IQ-DNA adducts (5.5 adducts/10(7) nucleotides) were 11-fold higher than those of PhIP or MeIQx. The stomach contents, liver, kidney and urine of pups nursed by dams given radiolabeled IQ, MeIQx or PhIP were radioactive, indicating that these carcinogens (and/or metabolites) were excreted into breast milk and absorbed by the pups. After a 6 h suckling period, the amount of PhIP-derived radioactivity in the stomach contents of the pups was approximately 10-fold higher than that seen with IQ or MeIQx. Urine from pups from the three groups was mutagenic in the Ames assay with Salmonella TA98 in the presence of an S9 activating system. IQ-, MeIQx- and PhIP-DNA adducts, at levels in the range of 0.25-0.46 adducts per 10(8) nucleotides, were detected in the livers of pups using the P-32-postlabeling method under intensification conditions. The results from this study indicate that breast milk is a route of exposure of the newborn to heterocyclic amines. The presence of DNA adducts in the tissues of pups further suggests that this route of exposure may have a carcinogenic consequence to the newborn. RP GHOSHAL, A (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 37 TC 31 Z9 33 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 NOV PY 1993 VL 14 IS 11 BP 2199 EP 2203 DI 10.1093/carcin/14.11.2199 PG 5 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000001 PM 8242844 ER PT J AU DIWAN, BA HENNEMAN, JR NIMS, RW RICE, JM AF DIWAN, BA HENNEMAN, JR NIMS, RW RICE, JM TI TUMOR PROMOTION BY AN ANTICONVULSANT AGENT, PHENYTOIN, IN MOUSE-LIVER - CORRELATION WITH CYP2B INDUCTION SO CARCINOGENESIS LA English DT Article ID HEPATIC HYPERPLASTIC NODULES; N-NITROSODIETHYLAMINE; PHENOBARBITAL PROMOTION; ENZYME-INDUCTION; ALTERED FOCI; F344 RATS; EXPRESSION; MICE; DIETHYLNITROSAMINE; DIPHENYLHYDANTOIN AB To investigate the liver tumor promoting effects of phenytoin (5,5-diphenylhydantoin; DPH), 5 week old male D2B6F1 mice were given a single i.p. dose of 90 mg N-nitrosodiethylamine (NDEA)/kg body wt in tricaprylin. Control groups received tricaprylin alone. After 2 weeks, the mice were given a diet containing 500, 250 or 125 p.p.m. DPH. Ten mice from each treatment group were killed at 30 weeks of age, at which time 10/10 mice given 500 p.p.m. DPH after NDEA initiation had developed multiple hepatocellular foci and adenomas. Such lesions were found only in 2/10 mice given NDEA alone. By 60 weeks, when the experiment was concluded, the incidences (and multiplicities, in units of tumors per tumor-bearing mouse) of hepatocellular adenomas were 60% (1.8 +/- 0.8), 100% (11.6 +/- 5.5), 77% (4.4 +/- 3.3) or 71% (2.6 +/- 1.3) in mice exposed to NDEA alone, or NDEA followed by 500, 250 or 125 p.p.m. DPH respectively. Hepatocellular carcinomas (87% incidence) and hepatoblastomas (33% incidence) were found only in mice given 500 p.p.m. DPH following NDEA initiation. Dose-dependent and profound increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylase activity were detected in livers of B6C3F1 mice exposed for 14 days to dietary DPH (125, 250, 500 or 1000 p.p.m.). Similar increases in this activity were observed in D2B6F1 mice exposed to 500 and 250 p.p.m. for 30 or 60 weeks. Thus, increased hepatic CYP2B activity in mice exposed to DPH correlates with the tumor promoting effect of this compound. C1 NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RP DIWAN, BA (reprint author), DYNCORP, PROGRAM RESOURCES INC, BIOL CARCINOGENIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 37 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1993 VL 14 IS 11 BP 2227 EP 2231 DI 10.1093/carcin/14.11.2227 PG 5 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000004 PM 8242847 ER PT J AU CHANG, RL BATTISTA, S WONG, CQ KUMAR, S KOLE, PL SIKKA, HC BALANI, SK JERINA, DM CONNEY, AH WOOD, AW AF CHANG, RL BATTISTA, S WONG, CQ KUMAR, S KOLE, PL SIKKA, HC BALANI, SK JERINA, DM CONNEY, AH WOOD, AW TI BACTERIAL AND MAMMALIAN-CELL MUTAGENICITY OF 4 OPTICALLY-ACTIVE BAY-REGION 10,11-DIOL-8,9-EPOXIDES OF THE NITROGEN HETEROCYCLE DIBENZ[A,H]ACRIDINE SO CARCINOGENESIS LA English DT Article ID DIASTEREOMERIC BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; DIOL-EPOXIDES; NEWBORN MICE; MOUSE SKIN; EXCEPTIONAL ACTIVITY; ENANTIOMERS; TUMORIGENICITY; 3,4-DIOL-1,2-EPOXIDES; BENZ(A)ANTHRACENE; BENZACRIDINE AB The mutagenic activities of the enantiomers of the diastereomeric pair of bay-region 10,11-diol-8,9-epoxides of dibenz[a,h]acridine (DB[a,h]ACR) were evaluated in histidine-dependent strains of Salmonella typhimurium and in cultured Chinese hamster V79 cells. In strains TA98 and TA100 of S.typhimurium, the (-)-[8S,9R,10R,11S] diol-epoxide was the most mutagenic compound, inducing 1200 and 6900 His+ revertants/nmol respectively. The mutagenic activity of each of the remaining three isomers was essentially independent of the bacterial strain used and had 14-72% of the activity of the [S,R,R,S] isomer. However, in Chinese hamster V79 cells, the (+)-[8R,9S,10S,11R] diol-epoxide was the most mutagenic compound (68 8-azaguanine resistant variants/nmol/10(5) cells), inducing from 2 to 11 times as many mutations as the other three isomers. These results are analogous to previous studies with the bay-region diol-epoxides of other polycyclic hydrocarbons in that the isomer with [R,S,S,R] absolute configuration has had variable activity in the bacterial assays, but has generally been the most active in the mammalian cells. Furthermore, this isomer has almost always been highly tumorigenic in the mouse. C1 HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT ONCOL,NUTLEY,NJ 07110. SUNY COLL BUFFALO,CTR ENVIRONM RES,DIV ENVIRONM TOXICOL & CHEM,BUFFALO,NY 14222. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP CHANG, RL (reprint author), RUTGERS UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08855, USA. FU NCEH CDC HHS [NIEHS ESO-3346]; NCI NIH HHS [CA49756] NR 30 TC 11 Z9 11 U1 0 U2 2 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 NOV PY 1993 VL 14 IS 11 BP 2233 EP 2237 DI 10.1093/carcin/14.11.2233 PG 5 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000005 PM 8242848 ER PT J AU HENNINGS, H GLICK, AB LOWRY, DT KRSMANOVIC, LS SLY, LM YUSPA, SH AF HENNINGS, H GLICK, AB LOWRY, DT KRSMANOVIC, LS SLY, LM YUSPA, SH TI FVB N MICE - AN INBRED STRAIN SENSITIVE TO THE CHEMICAL INDUCTION OF SQUAMOUS-CELL CARCINOMAS IN THE SKIN SO CARCINOGENESIS LA English DT Article ID DIFFERENT MOUSE STRAINS; TRANSGENIC MICE; HA-RAS; MALIGNANT CONVERSION; TUMOR PROGRESSION; FEMALE SENCAR; CD-1 MICE; CARCINOGENESIS; BINDING; ONCOGENE AB The widespread use of FVB/N mice for the establishment of transgenic lines containing active oncogenes suggested the importance of testing the parent FVB/N mice for sensitivity to experimental carcinogenesis. After initiation of mouse skin by a single treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by 20 weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), the skin tumor incidence was compared in FVB/N mice, TPA-sensitive (SENCAR and CD-1) and TPA-resistant mice (BALB/c and C57BL/6). Initiation by 25 mug DMBA followed by promotion with a low dose of TPA (2 mug/week) induced one or more papillomas in only 25% of FVB/N mice, compared with 100% in SENCAR, 53% in CD-1, 17% in BALB/c and 0% in C57BL/6 mice. At a more effective dose of TPA (5 mug/week), FVB/N mice initiated by 5, 25 or 100 mug DMBA developed 3.4, 6.9 and 11.8 papillomas per mouse. In contrast, the incidence of squamous cell carcinomas (SCCs) (17-18/30 mice) did not increase with DMBA dose. TPA promotion of non-initiated mice induced only six papillomas, but three progressed to SCCs, a high rate of malignant conversion. Skin tumor induction by 20 weekly treatments with 10 mug DMBA produced few papillomas, but 50.0% of the papillomas progressed to carcinomas in FVB/N mice, compared with 9.15% in SENCAR, 37.5% in CD-1, 23.1% in BALB/c and 15.0% in C57CL/6 mice. The first carcinomas appeared after 14 weeks in FVB/N, 24 weeks in SENCAR, 26 weeks in CD-1 and C57BL/6 and 34 weeks in BALB/c mice. Thus, FVB/N mice develop an unusually high incidence of SCCs after treatment with repeated DMBA, DMBA initiation - TPA promotion and even TPA alone. C1 BIOCON INC,ROCKVILLE,MD. RP HENNINGS, H (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892, USA. NR 36 TC 115 Z9 117 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 NOV PY 1993 VL 14 IS 11 BP 2353 EP 2358 DI 10.1093/carcin/14.11.2353 PG 6 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000023 PM 8242866 ER PT J AU LIJINSKY, W AF LIJINSKY, W TI LIFE-SPAN AND CANCER - THE INDUCTION TIME OF TUMORS IN DIVERSE ANIMAL SPECIES TREATED WITH NITROSODIETHYLAMINE SO CARCINOGENESIS LA English DT Article ID N-NITROSODIETHYLAMINE; CARCINOGENIC AGENTS; AQUARIUM FISH; DIETHYLNITROSAMINE; RATS; CYTOCHROME-P-450; NITROSAMINE; INGESTION; EXPOSURE; LIVER AB To ascertain the possible relationship between animal lifespan and the rate of tumor development, the results of carcinogenesis studies in various species treated with similar doses of a carcinogenic nitrosamine have been compiled from the literature. Comparable experiments in 20 species of mammals, reptiles, birds, amphibians and fish were analyzed. The animals received approximately 1000 mg/kg body wt (400-2500 mg/kg) lifetime total dose of nitrosodiethylamine (NDEA). Animals with lifespans varying from 3 years (mouse) to > 50 years (snake) developed tumors with latent periods of roughly 1 year (range 0.5-1.9 year), showing no relationship to lifespan. The evidence suggests that the time dependence of tumor development is more likely related to the cumulative dose of carcinogen than to lifespan and the rate of aging. C1 NIEHS,DBRA,RES TRIANGLE PK,NC 27709. NR 45 TC 22 Z9 22 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 NOV PY 1993 VL 14 IS 11 BP 2373 EP 2375 DI 10.1093/carcin/14.11.2373 PG 3 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000026 PM 8242869 ER PT J AU LIU, Y SUNDQVIST, K BELINSKY, SA CASTONGUAY, A TJALVE, H GRAFSTROM, RC AF LIU, Y SUNDQVIST, K BELINSKY, SA CASTONGUAY, A TJALVE, H GRAFSTROM, RC TI METABOLISM AND MACROMOLECULAR INTERACTION OF THE TOBACCO-SPECIFIC CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN CULTURED EXPLANTS AND EPITHELIAL-CELLS OF HUMAN BUCCAL MUCOSA SO CARCINOGENESIS LA English DT Article ID MASS-SPECTROMETRIC ANALYSIS; RAT ORAL-TISSUE; N-NITROSAMINES; LUNG-CANCER; CHEMICAL CARCINOGENESIS; GROWTH-REGULATION; LIVER-MICROSOMES; DNA ADDUCTS; F344 RATS; N'-NITROSONORNICOTINE AB Metabolism and macromolecular interaction of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were studied in human buccal mucosa in vitro. Microautoradiographic analysis of [5-H-3]NNK-exposed explant cultures demonstrated a uniform distribution of bound radioactivity in the mucosal epithelium, without significant binding in the underlying connective tissue. The metabolism of [5-H-3]NNK at concentrations of both 6 and 100 muM resulted in seven identified metabolites in both explant and epithelial cell cultures. Formation of 4-(methylnitros-amino)-1-(3-pyridyl)butan-1-ol by carbonyl reduction of NNK accounted for almost 95% of the total metabolism, whereas the proportions of other metabolites obtained by alpha-carbon hydroxylation and pyridine N-oxidation reactions varied from undetectable levels to approximately 2% in both experimental systems. A positive correlation between concentration and the metabolic route associated with the formation of DNA methylating intermediates (alpha-hydroxylation at the N-methylene carbon) was found, i.e. when the concentration of NNK was raised from 6 to 100 muM, keto-acid formation which in part reflects DNA methylation was increased preferentially over ketoalcohol production, an index of DNA pyridyloxobutylation. Both the total rate of NNK metabolism and the amount of protein adducts were higher in cells from primary cultures up to the third passage than in explants cultured for 1 day. Between 10(-9) to 10(-4) M, neither NNK nor its precursor alkaloid nicotine affected the colony forming efficiency of normal and tumorous buccal epithelial cells, although at 10(-3) M each agent inhibited this function. Taken together, the results demonstrate the capability of human buccal mucosal epithelium to metabolize NNK by three major pathways, including those involved in the formation of adducts with cellular macromolecules. C1 KAROLINSKA INST,INST ENVIRONM MED,DIV TOXICOL,S-17177 STOCKHOLM,SWEDEN. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV LAVAL,SCH PHARM,CANC ETIOL & CHEMOPREVENT LAB,QUEBEC CITY G1K 7P4,QUEBEC,CANADA. UNIV UPPSALA,CTR BIOMED,DEPT PHARMACOL & TOXICOL,S-75123 UPPSALA,SWEDEN. RI Grafstrom, Roland/N-7217-2016 NR 45 TC 22 Z9 23 U1 0 U2 2 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 NOV PY 1993 VL 14 IS 11 BP 2383 EP 2388 DI 10.1093/carcin/14.11.2383 PG 6 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000028 PM 8242870 ER PT J AU KANNO, J MARONPOT, RR TAKAHASHI, M KASUGA, T HAYASHI, Y AF KANNO, J MARONPOT, RR TAKAHASHI, M KASUGA, T HAYASHI, Y TI REGRESSIVE AND NON-REGRESSIVE THYROID LESIONS OF THE RAT INDUCED BY SINGLE INJECTION OF N-BIS(2-HYDROXYPROPYL)NITROSAMINE AND IODINE DEFICIENT DIET SO CARCINOGENESIS LA English DT Article ID REVERSIBILITY; CARCINOGENESIS; ENHANCEMENT; TUMORS; GLAND AB Six-week-old male F344 rats were divided into 4 groups. Rats in Groups 1 (n = 16) and 3 (n = 14) received a s.c. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN) (2800 mg/kg) in experimental week 1 while rats in Groups 2 (n = 5) and 4 (n = 5) received saline. From weeks 2-20, all rats were given an iodine deficient (I-def) diet and tap water. Groups 1 and 2 were killed for the measurements of thyroid-stimulating hormone (TSH), thyroxine (T4), the maximum thyroid width (MTW), thyroid weight, morphology, morphometrics and proliferating cell nuclear antigen (PCNA) labeling index (LI). The thyroids of the rats in Group 3 and 4 were surgically exposed and the MTWs were measured. These latter rats were given basal diet for 6 weeks to recover from iodine deficiency, and then killed for the same measurements. Thyroid nodular lesions in Group 1 rats were classified into rive categories (NL0, NL1, NL2, NL3 and NL4) based upon incremental cellular and structural atypia. Two types of regressive nodules (NL'0 and NL'1+2) were identified in the recovered rats as the regressed form of NL0, NL1 and NL2 lesions. NL3 and NL4 nodules were seen in Groups 1 and 3. The mean number of combined NL0, NL1 or NL2 lesions was 28.44 +./- 6.12 nodules per rat (NPR) in Group 1 rats and the mean number of NL'0 and NL'1+2 lesions was 28.07 +/- 13.05 NPR in Group 3 rats. The mean number of NL3 or NL4 lesions was 1.70 NPR in Group 1 rats and 3.42 NPR in Group 3 rats. The LIs were NL0 (6.4 +/- 2.5%), NL1 (7.7 +/- 4.4%), NL2 (0.7 +/- 0.3%), NL3 (7.5 +/- 1.3%) and NL4 (14.4 +/- 5.3%) in Group 1 rats and NL'0 (<0.001%), NL'1+2 (<0.01%), NL3 (9.0 +/- 4.4%) and NL4 (23.3 +/- 17.8%) in Group 3 rats. The thyroid weights o Group 4 rats were 41 % of Group 2 rats. The volume fraction (VF) of the non-NL3, non-NL4 areas in Group 3 rats was 40% of that in Group 1 rats. However, the VF of NL3 or NL4 lesions in Group 3 rats was 520% of that of Group 1 rats. In summary, the growth of the NL0, NL1 and NL2 lesions was TSH-dependent, whereas NL3 and NL4 lesions were TSH-independent. In conclusion, affirmative morphological criteria were established to determine growth dependency on sustained serum TSH for thyroid nodular lesions induced in F344 rats by DHPN and 1-def diet. C1 TOKYO MED & DENT UNIV,FAC MED,DEPT PATHOL,BUNKYO KU,TOKYO 113,JAPAN. NATL INST HYG SCI,BIOL SAFETY RES CTR,DIV PATHOL,SETAGAYA KU,TOKYO 158,JAPAN. RP KANNO, J (reprint author), NIEHS,EXPTL PATHOL LAB,ENVIRONM CARCINOGENESIS PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 2 Z9 2 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 NOV PY 1993 VL 14 IS 11 BP 2389 EP 2396 PG 8 WC Oncology SC Oncology GA MH920 UT WOS:A1993MH92000029 PM 7902219 ER PT J AU ROSSOUW, JE GOTTO, AM AF ROSSOUW, JE GOTTO, AM TI DOES LOW-CHOLESTEROL CAUSE DEATH SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Editorial Material DE CHOLESTEROL; MORTALITY; METAANALYSIS; DRUG THERAPY; CONFOUNDING FACTORS; EPIDEMIOLOGY ID CORONARY HEART-DISEASE; LOWERING CHOLESTEROL; PREVENTION TRIALS; SERUM-CHOLESTEROL; MORTALITY; SUICIDE AB Data linking low cholesterol with excess mortality have been gathered from both observational and clinical trials. The data are probably unrelated, as the levels of total cholesterol associated with excess mortality in observational studies are well below 160 mg/dl (4.1 mmol/l), whereas the levels achieved in clinical trials average around 230 mg/dl (5.9 mmol/l). Likely explanations of the association are that low cholesterol is a consequence of disease or is a confounder associated with other variables. The authors assess the relevance of the data to public health policy and medical practice. They conclude that evidence suggesting low cholesterol is a cause of excess mortality currently lacks breadth and rigor, and find no basis for changing cholesterol-management guidelines. C1 BAYLOR COLL MED,DEPT MED,SM-1423,6550 FANNIN,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. NHLBI,BETHESDA,MD 20892. NR 21 TC 12 Z9 12 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD NOV PY 1993 VL 7 IS 5 BP 789 EP 793 DI 10.1007/BF00878932 PG 5 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA MP977 UT WOS:A1993MP97700007 PM 8110622 ER PT J AU WALKER, KE LAKATTA, EG HOUSER, SR AF WALKER, KE LAKATTA, EG HOUSER, SR TI AGE-ASSOCIATED CHANGES IN MEMBRANE CURRENTS IN RAT VENTRICULAR MYOCYTES SO CARDIOVASCULAR RESEARCH LA English DT Article DE MYOCARDIUM; ELECTROPHYSIOLOGY; AGING; IONIC CURRENTS ID CALCIUM CURRENT; K+ CURRENTS; SARCOPLASMIC-RETICULUM; CARDIAC MYOCYTES; ADULT-RATS; CELLS; MYOCARDIUM; HEART; TRANSIENT; CHANNELS AB Objective: Action potential duration of senescent rat ventricular myocytes is longer than in young adults. The aim of the study was to determine whether age related changes in L-type calcium current (I(Ca)), transient outward potassium current (I(TO)), and inwardly rectifying potassium current (I(KI)) are involved in the prolongation of the early (I(Ca), I(TO)) and late (I(KI)) portions of the rat action potential plateau. Methods: Whole cell voltage clamp techniques were used to study these currents in ventricular myocytes isolated from young (2-3 months), middle aged (8-9 months), and senescent (24-25 months) rats. Results: There were no differences in the magnitude of I(Ca) among age groups once currents were normalised for capacitative surface area. The voltage dependence of I(Ca) activation and steady state inactivation in the three age groups was also similar. At test potentials of 0 and +10 mV, there was a significant (p less-than-or-equal-to 0.05) slowing in the time course of inactivation of I(Ca); the time constants of inactivation increased with age [young v old in ms(SEM): 0 mV, 22.2(2.2) v 38.0(5.0) (slow); +10 mV, 8.0(2.0) v 15.6(2.0) (fast)]. With internal EGTA to buffer intracellular Ca2+, no significant age related differences in action potential duration or the time course of I(Ca) inactivation were observed. There was an age associated decrease in peak I(TO) density in the old (n = 25) compared to the young (n = 25) cell group (p < 0.05). The only age associated change in the kinetic properties of I(TO) was a small but consistent slowing in the time constants of inactivation at most test voltages measured, with significance occurring at 0 mV in the slow (tau2) Component. Conclusions: I(Ca) density is maintained in senescence; I(Ca) inactivation, however, is slowed. Age related differences in action potential duration and I(Ca) inactivation were reduced by buffering intracellular Ca2+. I(TO) channels appear to retain normal function through the aging process but overall there is a reduced channel density. The age associated changes in these currents should contribute to prolongation of action potential duration of the early plateau phase seen in the senescent rat. C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT PHYSIOL,3420 N BROAD ST,PHILADELPHIA,PA 19140. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. NIA,CTR GERONTOL,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. FU NHLBI NIH HHS [HL-33648, HL-33921] NR 33 TC 92 Z9 96 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV PY 1993 VL 27 IS 11 BP 1968 EP 1977 DI 10.1093/cvr/27.11.1968 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MH259 UT WOS:A1993MH25900016 PM 8287405 ER PT J AU VARTERASIAN, M LIPKOWITZ, S KARSCHMIZRACHI, I PATERSON, B KIRSCH, I AF VARTERASIAN, M LIPKOWITZ, S KARSCHMIZRACHI, I PATERSON, B KIRSCH, I TI 2 NEW DROSOPHILA GENES RELATED TO HUMAN HEMATOPOIETIC AND NEUROGENIC TRANSCRIPTION FACTORS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID DEVELOPING NERVOUS-SYSTEM; DNA-BINDING MOTIF; T-CELL LEUKEMIA; MOLECULAR-CLONING; SCL GENE; HELIX; DIFFERENTIATION; TRANSLOCATION; LOCALIZATION; PROTEINS AB We have identified two new basic domain helix-loop-helix (bHLH) genes in Drosophila melanogaster, DroSCL and DroNHLH. DroSCL was identified because of its homology to the mammalian hematopoietic transcription factor SCL. DroNHLH was similarly identified by homology to NHLH1 and NHLH2, two bHLH genes expressed in the developing mammalian nervous system. A partial DroSCL complementary DNA clone was obtained from an early pupal (5.5-7.5-day) Drosophila library. DroSCL is 73% identical to SCL within the 55-amino acid region of the bHLH domain. A DroNHLH complementary DNA clone was obtained from an early instar (I and II) Drosophila library. Its coding region consists of 162 amino acids and encodes a predicted protein of 18,312 daltons. DroNHLH is 87% identical to NHLH1 and NHLH2 within the bHLH domain. DroSCL and DroNHLH are located on the X chromosome. A 1.7-kilobase DroSCL transcript and a 1.5-kilobase DroNHLH transcript were detected by Northern analysis of total Drosophila RNA. Examination of Drosophila embryos by tissue in situ hybridization reveals restricted expression of both genes in a subset of cells in the developing central nervous system. C1 NATL NAVAL MED CTR, NCI NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NCI, DIV CANC BIOL DIAG & CTR, BETHESDA, MD 20892 USA. NR 23 TC 11 Z9 12 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1993 VL 4 IS 11 BP 885 EP 889 PG 5 WC Cell Biology SC Cell Biology GA MF984 UT WOS:A1993MF98400002 PM 8297794 ER PT J AU TRESTON, AM SCOTT, FM VOS, M IWAI, N MAINS, RE EIPPER, BA CUTTITTA, F MULSHINE, JL AF TRESTON, AM SCOTT, FM VOS, M IWAI, N MAINS, RE EIPPER, BA CUTTITTA, F MULSHINE, JL TI BIOCHEMICAL-CHARACTERIZATION OF PEPTIDE ALPHA-AMIDATION ENZYME-ACTIVITIES OF HUMAN NEUROENDOCRINE LUNG-CANCER CELL-LINES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GLYCINE-EXTENDED PEPTIDES; BOMBESIN-LIKE PEPTIDES; MESSENGER-RNA; MONOOXYGENASE ACTIVITY; FUNCTIONAL EXPRESSION; STABLE INTERMEDIATE; TISSUE; ACID; IDENTIFICATION; BIOSYNTHESIS AB Peptide alpha-amidation is a posttranslational modification of approximately half of all endocrine and neuroendocrine peptide hormones, including several hormones with mitogenic effects for tumor cells, and is typically essential for complete hormonal bioactivity. alpha-Amidated peptide hormones have been reported to be autocrine growth factors for small cell lung cancer cells. We report here that a variety of human lung tumor cell lines express both enzymes required for the two-step conversion of inactive glycine-extended peptides into their active COOH-terminal alpha-amide analogues. Human tumor cell peptidylglycine alpha-amidation enzymes are present in multiple molecular forms. Both proteins are metalloenzymes which are present af highest concentrations in secretory granules in neuroendocrine cell lines. The expression of these enzymes is positively correlated with expression of other markers of the neuroendocrine phenotype, such as DOPA decarboxylase. Peptidylglycine alpha-amidating enzyme-specific activities are approximately 50-fold higher in extracts of endocrine cell lines (lung small cell and carcinoid) than of nonendocrine lines. Biochemical characterization of the peptidylglycine alpha-amidating enzymes will enable development of tools for detection of endocrine processes in the early stages of neoplasia and for interruption of autocrine stimulation pathways in tumor cells. C1 NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, INTERVENT SECT, ROCKVILLE, MD 20850 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. FU NIDA NIH HHS [DA-00266, DA-00097, DA-00098] NR 46 TC 20 Z9 20 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1993 VL 4 IS 11 BP 911 EP 920 PG 10 WC Cell Biology SC Cell Biology GA MF984 UT WOS:A1993MF98400005 PM 8297797 ER PT J AU BROTT, BK ALESSANDRINI, A LARGAESPADA, DA COPELAND, NG JENKINS, NA CREWS, CM ERIKSON, RL AF BROTT, BK ALESSANDRINI, A LARGAESPADA, DA COPELAND, NG JENKINS, NA CREWS, CM ERIKSON, RL TI MEK2 IS A KINASE RELATED TO MEK1 AND TS DIFFERENTIALLY EXPRESSED IN MURINE TISSUES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GENETIC-LINKAGE MAP; PHEROMONE RESPONSE PATHWAY; TYROSINE THREONINE KINASE; PROTEIN-KINASE; PHOSPHORYLATION; YEAST; PRODUCT; FAMILY; ERKS; LOCALIZATION AB MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine. We report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a protein of a molecular weight of 44,500. The MEK2 protein bears substantial sequence homology to MEK1, except at its amino terminus, and at a proline-rich region insert between the conserved kinase subdomains 9 and 10. MEK1 and MEK2 are shown to be encoded by different genes and are located on murine chromosomes 9 and 10, respectively. Northern analysis indicates that Mek2 is expressed at low levels in adult mouse brain and heart tissue, and at higher levels in other tissues examined. Low expression levels of Mek2 in brain tissue are in contrast to the high levels of Mek1 expressed in brain. Mek2 is expressed at high levels in neonatal brain, however. Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene family. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP BROTT, BK (reprint author), HARVARD UNIV,DEPT CELLULAR & DEV BIOL,16 DIVIN AVE,CAMBRIDGE,MA 02138, USA. RI Largaespada, David/C-9832-2014 FU NCI NIH HHS [CA42580, CA9282-01, N01-CO-74101] NR 57 TC 51 Z9 57 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1993 VL 4 IS 11 BP 921 EP 929 PG 9 WC Cell Biology SC Cell Biology GA MF984 UT WOS:A1993MF98400006 PM 8297798 ER PT J AU COHN, M MAGE, RG SCHARFF, MD CHASE, MW MCDEVITT, HO UHR, JW LAWRENCE, HS PICK, E NOSSAL, GJV FAUCI, AS AF COHN, M MAGE, RG SCHARFF, MD CHASE, MW MCDEVITT, HO UHR, JW LAWRENCE, HS PICK, E NOSSAL, GJV FAUCI, AS TI LANDY,MAURICE (1913-1993) - IN-MEMORIAM SO CELLULAR IMMUNOLOGY LA English DT Item About an Individual C1 NIAID,IMMUNOL LAB,MOLEC IMMUNOGENET SECT,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,CTR CANC,BRONX,NY 10461. ROCKEFELLER UNIV,NEW YORK,NY 10021. STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV TEXAS,SW MED CTR,RAYMOND WILLIE DISTINGUISHED CHAIR CANC RES,DALLAS,TX 75230. NYU,SCH MED,DIV INFECT DIS & IMMUNOL,NEW YORK,NY 10003. NYU,SCH MED,CTR AIDS RES,NEW YORK,NY 10003. TEL AVIV UNIV,DAVID & NATALIE ROBERTS CHAIR IMMUNOL,SACKLER FAC MED,IL-69978 TEL AVIV,ISRAEL. UNIV MELBOURNE,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3052,AUSTRALIA. NIAID,BETHESDA,MD 20892. RP COHN, M (reprint author), SALK INST BIOL STUDIES,LA JOLLA,CA 92037, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1993 VL 152 IS 1 BP 3 EP 6 PG 4 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MJ781 UT WOS:A1993MJ78100002 ER PT J AU HOLLADAY, SD BLAYLOCK, BL COMMENT, CE HEINDEL, JJ FOX, WM KORACH, KS LUSTER, MI AF HOLLADAY, SD BLAYLOCK, BL COMMENT, CE HEINDEL, JJ FOX, WM KORACH, KS LUSTER, MI TI SELECTIVE PROTHYMOCYTE TARGETING BY PRENATAL DIETHYLSTILBESTEROL EXPOSURE SO CELLULAR IMMUNOLOGY LA English DT Article ID TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; OSTEOBLAST-LIKE CELLS; ESTROGEN-RECEPTOR; MOUSE UTERUS; BONE-MARROW; MICE; INUTERO; RESPONSIVENESS; PROLIFERATION; PRECURSORS C1 NIEHS,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,IMMUNOTOXICOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,RECEPTOR BIOL GRP,RES TRIANGLE PK,NC 27709. RP HOLLADAY, SD (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,VIRGINIA MARYLAND REG COLL VET MED,DEPT BIOMED SCI,BLACKSBURG,VA 24061, USA. NR 49 TC 53 Z9 55 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1993 VL 152 IS 1 BP 131 EP 142 DI 10.1006/cimm.1993.1273 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MJ781 UT WOS:A1993MJ78100013 PM 8242756 ER PT J AU SASAMOTO, Y KAWANO, YI WIGGERT, B CHADER, GJ GREY, I AF SASAMOTO, Y KAWANO, YI WIGGERT, B CHADER, GJ GREY, I TI INDUCTION OF UNRESPONSIVENESS IN ADULT-RATS BY IMMUNODOMINANT AND NONDOMINANT PEPTIDES SO CELLULAR IMMUNOLOGY LA English DT Note ID RETINOID-BINDING PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; SPLEEN-CELLS; IRBP; SUPPRESSION; TOLERANCE; UVEORETINITIS; DETERMINANTS C1 NEI,IMMUNOL LAB,BLDG 10,RM 10N208,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 26 TC 2 Z9 2 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1993 VL 152 IS 1 BP 286 EP 292 DI 10.1006/cimm.1993.1289 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MJ781 UT WOS:A1993MJ78100029 PM 8242769 ER PT J AU WANG, SM MILNE, GWA AF WANG, SM MILNE, GWA TI APPLICATIONS OF COMPUTERS TO TOXICOLOGICAL RESEARCH SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ASSISTED STRUCTURE-ACTIVITY; POLYCYCLIC AROMATIC-HYDROCARBONS; CHEMICAL CARCINOGENS; PATTERN-RECOGNITION; SALMONELLA-TYPHIMURIUM; GENOTOXIC ACTIVITY; QSAR MODEL; DATA-BASE; DATA SET; MUTAGENICITY C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 49 TC 9 Z9 10 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV-DEC PY 1993 VL 6 IS 6 BP 748 EP 753 DI 10.1021/tx00036a002 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA MJ790 UT WOS:A1993MJ79000003 PM 8117912 ER PT J AU POHL, LR AF POHL, LR TI AN IMMUNOCHEMICAL APPROACH OF IDENTIFYING AND CHARACTERIZING PROTEIN TARGETS OF TOXIC REACTIVE METABOLITES SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID ALCOHOLIC LIVER-DISEASE; LOW-DENSITY-LIPOPROTEIN; CHLOROFLUOROCARBON SUBSTITUTE 2,2-DICHLORO-1,1,1-TRIFLUOROETHANE; HALOTHANE-INDUCED HEPATITIS; PHOSPHOLIPASE-C-ALPHA; ADDUCT FORMATION; ENDOPLASMIC-RETICULUM; DICLOFENAC HEPATITIS; ACETALDEHYDE ADDUCT; ACETAMINOPHEN HEPATOTOXICITY RP POHL, LR (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N 115,BETHESDA,MD 20892, USA. NR 101 TC 39 Z9 39 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV-DEC PY 1993 VL 6 IS 6 BP 786 EP 793 DI 10.1021/tx00036a006 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA MJ790 UT WOS:A1993MJ79000007 PM 8117916 ER PT J AU PUTNAM, FW HELMERS, K TRICKETT, PK AF PUTNAM, FW HELMERS, K TRICKETT, PK TI DEVELOPMENT, RELIABILITY, AND VALIDITY OF A CHILD DISSOCIATION SCALE SO CHILD ABUSE & NEGLECT LA English DT Article DE DISSOCIATION; MULTIPLE PERSONALITY DISORDER; SEXUAL ABUSE; DISSOCIATIVE DISORDER NOS ID MULTIPLE PERSONALITY-DISORDER; SYMPTOMS; ABUSE; EXPERIENCES; STATES AB Dissociation is a complex psychophysiological process that ranges along a continuum from minor, normal dissociation to Axis I psychopathology. High levels of dissociation are associated with increased self-destructive behaviors and other symptoms. Although several validated measures of dissociation exist for adults, no measures are available for children. The Child Dissociative Checklist (CDC) was developed to meet this need and is a reliable and valid observer report measure of dissociation in children. The CDC had a 1-year test-retest reliability coefficient of rho =.69 (N = 73, p =.0001) in a sample of normal and sexually abused girls. The CDC had high discriminant validity among four test samples including: normal control girls, sexually abused girls, boys and girls with dissociative disorder NOS and boys and girls with multiple personality disorder. The CDC is intended as a clinical screening instrument and as a research measure. The CDC is not designed to be used as a diagnostic instrument. C1 UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20982, USA. NR 52 TC 128 Z9 128 U1 4 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD NOV-DEC PY 1993 VL 17 IS 6 BP 731 EP 741 DI 10.1016/S0145-2134(08)80004-X PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA MK775 UT WOS:A1993MK77500004 PM 8287286 ER PT J AU LENFANT, C AF LENFANT, C TI THE PROGRAM PROJECT GRANT - A DELICATE BALANCE 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 NOV PY 1993 VL 88 IS 5 BP 2011 EP 2012 PN 1 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ME833 UT WOS:A1993ME83300001 ER PT J AU MANOLIO, TA FURBERG, CD SHEMANSKI, L PSATY, BM OLEARY, DH TRACY, RP BUSH, TL AF MANOLIO, TA FURBERG, CD SHEMANSKI, L PSATY, BM OLEARY, DH TRACY, RP BUSH, TL TI ASSOCIATIONS OF POSTMENOPAUSAL ESTROGEN USE WITH CARDIOVASCULAR-DISEASE AND ITS RISK-FACTORS IN OLDER WOMEN SO CIRCULATION LA English DT Article DE CARDIOVASCULAR DISEASES; AGING; EPIDEMIOLOGY; RISK FACTORS; HORMONES ID CORONARY HEART-DISEASE; FOLLOW-UP; CAROTID ATHEROSCLEROSIS; REPLACEMENT THERAPY; MORTALITY; HEALTH; COMMUNITY; ESTRADIOL; PLASMA AB Background. Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women. Methods and Results. Present and past estrogen use was ascertained in 2955 women greater-than-or-equal-to 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12% of these women and past use by an additional 26.5%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P<.0001). Estrogen users also had lower levels of subclinical disease as measured by carotid intimal-medial thickness, carotid stenosis grade, ECG left ventricular mass, and Doppler mitral peak flow velocities (each P<.02). Relations were similar in younger and older women (65 to 74 versus greater-than-or-equal-to 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids. Conclusions. Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life. C1 GEISINGER MED CLIN,DEPT RADIOL,DANVILLE,PA. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 301,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85081, N01-HC-85079] NR 37 TC 166 Z9 166 U1 2 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1993 VL 88 IS 5 BP 2163 EP 2171 PN 1 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ME833 UT WOS:A1993ME83300022 PM 8222111 ER PT J AU KONSTAM, MA KRONENBERG, MW ROUSSEAU, MF UDELSON, JE MELIN, J STEWART, D DOLAN, N EDENS, TR AHN, S KINAN, D HOWE, DM KILCOYNE, L METHERALL, J BENEDICT, C YUSUF, S POULEUR, H AF KONSTAM, MA KRONENBERG, MW ROUSSEAU, MF UDELSON, JE MELIN, J STEWART, D DOLAN, N EDENS, TR AHN, S KINAN, D HOWE, DM KILCOYNE, L METHERALL, J BENEDICT, C YUSUF, S POULEUR, H TI EFFECTS OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ENALAPRIL ON THE LONG-TERM PROGRESSION OF LEFT-VENTRICULAR DILATATION IN PATIENTS WITH ASYMPTOMATIC SYSTOLIC DYSFUNCTION SO CIRCULATION LA English DT Article DE VASODILATION; EJECTION FRACTION; HEART FAILURE ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CAPTOPRIL THERAPY; RATS; PREVENTION; STIFFNESS; IMAGE; INDEX AB Background. Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible. Methods and Results. One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction less-than-or-equal-to 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P<.05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119+/-28 to 124+/-33 mL/m2, mean+/-SD) and decreased in enalapril patients (120+/-25 to 113+/-25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P<.02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group. Conclusions. Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,HOUSTON,TX 77225. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT RADIOL,NASHVILLE,TN 37232. UNIV N CAROLINA,DEPT BIOSTAT,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC 27514. UNIV CATHOLIQUE LOUVAIN,SCH MED,DIV CARDIOL,B-1200 BRUSSELS,BELGIUM. UNIV CATHOLIQUE LOUVAIN,SCH MED,DIV NUCL MED,B-1200 BRUSSELS,BELGIUM. NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC55010] NR 25 TC 192 Z9 195 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1993 VL 88 IS 5 BP 2277 EP 2283 PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ME833 UT WOS:A1993ME83300034 PM 8222122 ER PT J AU LEE, SW TRAPNELL, BC RADE, JJ VIRMANI, R DICHEK, DA AF LEE, SW TRAPNELL, BC RADE, JJ VIRMANI, R DICHEK, DA TI IN-VIVO ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER INTO BALLOON-INJURED RAT CAROTID ARTERIES SO CIRCULATION RESEARCH LA English DT Article DE GENE THERAPY; BETA-GALACTOSIDASE; SMOOTH MUSCLE CELLS; GENE EXPRESSION ID SMOOTH-MUSCLE CELLS; EXPRESSION; WALL; GROWTH; PROLIFERATION; CORONARY; CATHETER; THERAPY; HEPARIN; MODEL AB We studied the ability of adenoviral vectors to achieve gene transfer into injured arteries. A recombinant adenoviral vector expressing a nuclear-targeted beta-galactosidase gene was constructed and infused into balloon-injured rat carotid arteries. Three days after gene transfer, recombinant gene expression was assessed quantitatively by (1) measuring beta-galactosidase antigen and activity in tissue extracts and (2) histochemical staining and counting of cells expressing beta-galactosidase. Exposure of injured carotid arteries to increasing concentrations of the vector (10(8) to 10(10) plaque-forming units per milliliter) resulted in a dose-responsive increase in beta-galactosidase expression, with peak expression of approximately 43 mU or 25 ng beta-galactosidase per vessel. Microscopic examination of histochemically stained arteries demonstrated gene transfer limited to the vascular media; transduced cells were identified immunohistochemically as smooth muscle cells. Counting of both histochemically stained and total nuclei in the media revealed that approximately 30% of the cells in the media of the injured vessels were transduced. Calculations based on both counting cells and on the level of beta-galactosidase expression in tissue extracts suggested the presence of 5000 to 10 000 transduced cells per 10 mm of vessel. Arteries infused with either vehicle only, a control adenoviral vector, or liposomes combined with the vector plasmid contained little or no evidence of beta-galactosidase expression. High levels of in vivo beta-galactosidase expression persisted for at least 7 days after gene transfer but declined significantly by day 14. We conclude that adenoviral vector-mediated gene transfer into the injured rat carotid artery results in efficient gene transfer into the vascular media, with levels of recombinant protein production significantly higher than any previously reported in arterial gene transfer studies. Adenoviral vectors appear to be particularly useful agents for in vivo arterial gene transfer. C1 NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D-18,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD. ARMED FORCES INST PATHOL,WASHINGTON,DC. JOHNS HOPKINS UNIV,DIV CARDIOL,BALTIMORE,MD 21218. NR 33 TC 209 Z9 210 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV PY 1993 VL 73 IS 5 BP 797 EP 807 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA MB798 UT WOS:A1993MB79800003 PM 8403251 ER PT J AU IWAMOTO, Y REICH, R NEMETH, G YAMADA, Y MARTIN, GR AF IWAMOTO, Y REICH, R NEMETH, G YAMADA, Y MARTIN, GR TI CYCLIC-AMP DECREASES CHEMOTAXIS, INVASIVENESS AND LUNG COLONIZATION OF H-RAS TRANSFORMED MOUSE FIBROBLASTS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE H-RAS; CYCLIC AMP; INVASION ID NIH 3T3 CELLS; PROTEIN KINASE-C; BASEMENT-MEMBRANE; METASTATIC PROPERTIES; ONCOGENE EXPRESSION; NIH/3T3 CELLS; TUMOR-CELLS; NUDE-MICE; PHENOTYPE; GENE AB We transfected mouse 10T1/2 fibroblasts with the H-ras oncogene and isolated lines expressing H-ras. One of the lines exhibited a highly malignant phenotype with the ability to produce large tumors and to colonize the lung after tail vein injection. In addition, the cells of this line showed increased collagenase IV production, directed migration and invasiveness, properties associated with the ability of tumor cells to metastasize. Since cyclic adenosine 3',5'-monophosphate (cAMP) is known to down-regulate ras expression, we exposed the malignant cells (Cl-1) to either N-6, 2',0-dibutyryl cAMP (DB-cAMP) or 8-bromo cAMP (8-Br-cAMP), either with or without a phosphodiesterase inhibitor. We found that these treatments reduced the expression of ras, chemotaxis, invasiveness, and lung colonization of the ras-transformed cells. We therefore postulate that the malignancy of some cells may be regulated by alterations in the intracellular cAMP levels by suppressing ras expression and/or by reducing other activities required for the dissemination of tumor cells. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP IWAMOTO, Y (reprint author), KYUSHU UNIV,FAC MED,DEPT ORTHOPAED SURG,HIGASHI KU,MAIDASHI 3-1-1,FUKUOKA 812,JAPAN. NR 36 TC 14 Z9 15 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD NOV PY 1993 VL 11 IS 6 BP 492 EP 501 DI 10.1007/BF00054940 PG 10 WC Oncology SC Oncology GA MH071 UT WOS:A1993MH07100006 PM 7693388 ER PT J AU SFIKAKIS, PP MCCUNE, BK TSOKOS, M ARONI, K VAYIOPOULOS, G TSOKOS, GC AF SFIKAKIS, PP MCCUNE, BK TSOKOS, M ARONI, K VAYIOPOULOS, G TSOKOS, GC TI IMMUNOHISTOLOGICAL DEMONSTRATION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN THE SKIN OF PATIENTS WITH SYSTEMIC-SCLEROSIS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID SCLERODERMA FIBROBLASTS; INSITU HYBRIDIZATION; I PROCOLLAGEN; MESSENGER-RNA; COLLAGEN; FACTOR-BETA-1; LOCALIZATION; STIMULATION; EXPRESSION; PATHOGENESIS C1 WALTER REED ARMY MED CTR,DEPT CLIN INVEST,WASHINGTON,DC 20012. UNIV ATHENS,SCH MED,DEPT MED 1,ATHENS,GREECE. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP SFIKAKIS, PP (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. RI Aroni, Kyriaki/B-8331-2009 NR 30 TC 57 Z9 57 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1993 VL 69 IS 2 BP 199 EP 204 DI 10.1006/clin.1993.1170 PG 6 WC Immunology; Pathology SC Immunology; Pathology GA MC285 UT WOS:A1993MC28500011 PM 8403557 ER PT J AU NGUYEN, BY LANDUCCI, DL CUNNION, RE YARCHOAN, R WALKER, RE AF NGUYEN, BY LANDUCCI, DL CUNNION, RE YARCHOAN, R WALKER, RE TI A CASE OF HYPERDYNAMIC SHOCK CAUSED BY TRIMETHOPRIM-SULFAMETHOXAZOLE IN WHICH NO TUMOR-NECROSIS-FACTOR OR FEATURES OF ANAPHYLAXIS WERE DETECTED SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID PNEUMOCYSTIS-CARINII PNEUMONIA; HUMAN-IMMUNODEFICIENCY-VIRUS; SEPTIC SHOCK; AIDS AB An unusual acute hypotensive syndrome has been observed in association with administration of trimethoprim-sulfamethoxazole (TMP-SMZ) to patients with human immunodeficiency virus (HIV) infection. In the 11 cases that have been reported, the syndrome differs from classic anaphylaxis and resembles septic shock. Mediation by tumor necrosis factor (TNF) has been hypothesized, but the mechanism has not been characterized with cytokine assays, and no invasive hemodynamic measurements have been reported. We describe a case of recurrent hyperdynamic shock-without classic features of anaphylaxis, without detectable IgE antibodies against TMP or SMZ, and without detectable levels of TNF-involving an HIV-infected patient rechallenged with TMP-SMZ. C1 NIAID,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP NGUYEN, BY (reprint author), NCI,CLIN ONCOL PROGRAM,MED BRANCH,BLDG 10,ROOM 12-N-226,BETHESDA,MD 20892, USA. NR 14 TC 15 Z9 15 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 NOV PY 1993 VL 17 IS 5 BP 885 EP 887 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ME523 UT WOS:A1993ME52300011 PM 8286631 ER PT J AU ROILIDES, E PIZZO, PA AF ROILIDES, E PIZZO, PA TI PERSPECTIVES ON THE USE OF CYTOKINES IN THE MANAGEMENT OF INFECTIOUS COMPLICATIONS OF CANCER SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COLONY-STIMULATING FACTOR; CELL LUNG-CANCER; ASPERGILLUS HYPHAE; INTERFERON-GAMMA; MACROPHAGE; CHEMOTHERAPY; NEUTROPENIA; INVIVO; CSF; NEUTROPHILS AB Treatment of neoplastic diseases is followed by a variety of infectious complications. Neutropenia and functional defects of phagocytes are common consequences of cancer and its treatment and contribute to an increased susceptibility to infections. Cytokines with hematopoietic growth stimulatory and/or immunoenhancing properties, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-3, interferon-gamma, macrophage colony-stimulating factor, interleukin-1, and interleukin-6 have been shown to either have clinical utility in patients with cancer and neutropenia or offer the promise to do so. GM-CSF and G-CSF, for example, have been shown to reduce the incidence of fever and infectious complications in patients with cancer and neutropenia. The role of cytokines for the treatment of defined infections (e.g., invasive mycoses) is under investigation. C1 NCI,INFECT DIS SERV,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 29 TC 11 Z9 11 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 NOV PY 1993 VL 17 SU 2 BP S385 EP S389 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MF187 UT WOS:A1993MF18700015 PM 7506061 ER PT J AU WALSH, TJ LEE, JW AF WALSH, TJ LEE, JW TI PREVENTION OF INVASIVE FUNGAL-INFECTIONS IN PATIENTS WITH NEOPLASTIC DISEASES SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID BONE-MARROW TRANSPLANTATION; ACUTE NONLYMPHOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; PLUS AMPHOTERICIN-B; CANCER-PATIENTS; NEUTROPENIC PATIENTS; CANDIDA-KRUSEI; GRANULOCYTOPENIC PATIENTS; PULMONARY ASPERGILLOSIS; ORAL CANDIDIASIS AB Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 122 TC 29 Z9 29 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 NOV PY 1993 VL 17 SU 2 BP S468 EP S480 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MF187 UT WOS:A1993MF18700028 PM 8274613 ER PT J AU BALTZ, JK MONTELLO, MJ AF BALTZ, JK MONTELLO, MJ TI CLADRIBINE FOR THE TREATMENT OF HEMATOLOGIC MALIGNANCIES SO CLINICAL PHARMACY LA English DT Review DE ANTINEOPLASTIC AGENTS; CLADRIBINE; COSTS; DOSAGE; DRUG ADMINISTRATION; LEUKEMIA; MECHANISM OF ACTION; PHARMACOKINETICS; STORAGE; TOXICITY AB The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenstrom's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is $3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL. RP BALTZ, JK (reprint author), NCI,CANC THERAPY EVALUAT PROGRAM,PHARMACEUT MANAGEMENT BRANCH,EPN 804,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 12 U1 1 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0278-2677 J9 CLIN PHARMACY PD NOV PY 1993 VL 12 IS 11 BP 805 EP 813 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ME039 UT WOS:A1993ME03900010 PM 7903917 ER PT J AU BARRETT, KC ZAHNWAXLER, C COLE, PM AF BARRETT, KC ZAHNWAXLER, C COLE, PM TI AVOIDERS VS AMENDERS - IMPLICATIONS FOR THE INVESTIGATION OF GUILT AND SHAME DURING TODDLERHOOD SO COGNITION & EMOTION LA English DT Article ID SEX-DIFFERENCES; EMOTIONAL DEVELOPMENT; SELF; DEPRESSION; AGGRESSION; VALIDATION; PRONENESS; BEHAVIOR; GENDER; ROLES AB Recent research and theory highlights the distinctive features of shame vs. guilt, as well as the important implications of that distinction for typical and atypical behaviour regulation. Briefly, shame is characterised by withdrawal and hiding from judgemental others, and guilt by making amends-repairing and confessing. The present study was aimed at determining whether a shame-relevant and a guilt-relevant pattern of responses to a standard violation could be distinguished in toddlers. Two-year-old children participated in a play session, during which a mishap occurred that the children appeared to have caused. Based upon whether or not children avoided the experimenter (E) after the mishap, they were dichotomised into a shame-relevant group of subjects (Avoiders) who avoid E after the mishap, are slow to make reparation, and are slow to tell E about the mishap; and a guilt-relevant group (Amenders) showing the opposite pattern. All guilt-relevant behaviours were greater for Amenders than Avoiders, and all but one shame-relevant behaviour was greater for Avoiders than for Amenders, suggesting coherence in the organisation of responses. Moreover, convergent evidence from a maternal report questionnaire indicated that in non-laboratory settings as well, Amenders manifested greater guilt relative to shame than did Avoiders. Further research is needed to determine developmental antecedents and consequences of the Avoider/Amender dichotomy. C1 NIMH,BETHESDA,MD 20892. RP BARRETT, KC (reprint author), COLORADO STATE UNIV,DEPT HUMAN DEV & FAMILY STUDIES,FT COLLINS,CO 80523, USA. NR 52 TC 73 Z9 75 U1 4 U2 16 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PD NOV PY 1993 VL 7 IS 6 BP 481 EP 505 DI 10.1080/02699939308409201 PG 25 WC Psychology, Experimental SC Psychology GA MJ886 UT WOS:A1993MJ88600001 ER PT J AU WHITCUP, SM NUSSENBLATT, RB PRICE, FW CHAN, CC AF WHITCUP, SM NUSSENBLATT, RB PRICE, FW CHAN, CC TI EXPRESSION OF CELL-ADHESION MOLECULES IN CORNEAL GRAFT FAILURE SO CORNEA LA English DT Article DE CELL ADHESION MOLECULES; GRAFT FAILURE AB Corneal graft failure is frequently mediated by uncontrolled inflammatory disease. We studied the expression of cell adhesion molecules in seven penetrating keratoplasty specimens with graft failure and in a normal eye bank cornea using immunohistochemical staining and monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1, CD54), lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and major histocompatibility complex (MHC) class II antigen (HLA-DR). ICAM-1 and HLA-DR were expressed on keratocytes and the corneal endothelium in six of the seven specimens. ICAM-1 expression was strongest in the corneas with the most severe inflammation (corneal allograft rejection and severe intraocular inflammation). LFA-1 is a counter-receptor for ICAM-1, and infiltration with leukocytes expressing either the alpha or beta chain of LFA-1 was found in areas of ICAM-1 expression in four of the seven corneas. In contrast, E-selectin was expressed in the stroma in only two specimens, and VCAM-1 in one specimen. Expression of cell adhesion molecules or MHC class II antigen were not detected in the normal eye bank cornea. These data suggest that ICAM-1 expression may play an important role in the development of corneal graft failure. Furthermore, monoclonal antibodies to block ICAM-1 or its ligands may inhibit the development of corneal inflammation. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. NR 0 TC 30 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1993 VL 12 IS 6 BP 475 EP 480 DI 10.1097/00003226-199311000-00003 PG 6 WC Ophthalmology SC Ophthalmology GA MC491 UT WOS:A1993MC49100003 PM 7505216 ER PT J AU CHREST, FJ BUCHHOLZ, MA KIM, YH KWON, TK NORDIN, AA AF CHREST, FJ BUCHHOLZ, MA KIM, YH KWON, TK NORDIN, AA TI IDENTIFICATION AND QUANTITATION OF APOPTOTIC CELLS FOLLOWING ANTI-CD3 ACTIVATION OF MURINE G(0) T-CELLS SO CYTOMETRY LA English DT Article DE MULTIPARAMETER; CELL SORTING; NECROTIC; CELL CYCLE; CD4; CD8; LIGHT SCATTER ID CD3/T-CELL RECEPTOR COMPLEX; FLOW-CYTOMETRY; LYMPHOCYTES-T; DEATH; THYMOCYTES; FRAGMENTATION; LIGATION AB Multiparameter flow cytometry and cell sorting were used to examine the process of apoptosis after activation of murine resting T cells with immobilized anti-CD3. Activated T cells treated with Hoechst 33342 (HO-33342) and analyzed by flow cytometry showed two major cell populations of high and low fluorescence. These populations were sorted and the DNA extracted and subjected to electrophoresis. Electrophoresis of DNA extracted from T cells showing a low level of HO-33342 fluorescence (HO-Low) resulted in a typical ladder pattern characteristic of internucleosomal DNA degradation associated with apoptosis, whereas the cellular DNA of the cells showing a high level of fluorescence (HO-High) showed a narrow high molecular weight band. Multiparameter analysis further indicated that cells with HO-High characteristics possessed corresponding high-FSC/low-SSC properties, whereas HO-Low cells formed a cluster of low-FSC/high-SSC cells. Analysis of the DNA extracted from cells sorted on the basis of scatter properties alone confirmed that the low-FSC/high-SSC population contained the apoptotic cells and that the high-FSC/low-SSC population was comprised of viable cells. This methodology allowed us to determine the percentage of apoptotic cells following anti-CD3 activation at various time points and to discriminate them from those in cell cycle. We could further quantitate the number of apoptotic versus viable CD4+ and CD8 + cells in the cell cycle. (C) 1993 Wiley-Liss, Inc.* RP CHREST, FJ (reprint author), NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 21 TC 31 Z9 31 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 0196-4763 J9 CYTOMETRY JI Cytometry PD NOV PY 1993 VL 14 IS 8 BP 883 EP 890 DI 10.1002/cyto.990140806 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ME841 UT WOS:A1993ME84100005 PM 7507023 ER PT J AU ROTHENPIELER, UW DRESSLER, GR AF ROTHENPIELER, UW DRESSLER, GR TI PAX-2 IS REQUIRED FOR MESENCHYME-TO-EPITHELIUM CONVERSION DURING KIDNEY DEVELOPMENT SO DEVELOPMENT LA English DT Article DE PAX-2; KIDNEY DEVELOPMENT; ANTISENSE ID HOMEOBOX-CONTAINING GENE; LAMININ-A-CHAIN; PAIRED-BOX; ANTISENSE OLIGONUCLEOTIDES; WAARDENBURG SYNDROME; EXPRESSION; MUTATION; OLIGODEOXYNUCLEOTIDE; MORPHOGENESIS; INDUCTION AB The conversion of mesenchyme to epithelium during the embryonic development of the mammalian kidney requires reciprocal inductive interactions between the ureter and the responding metanephric mesenchyme. The Pax-2 gene is activated in the mesenchyme in response to induction and is subsequently downregulated in more differentiated cells derived from the mesenchyme. Pax-2 belongs to a family of genes, at least three of which encode morphogenetic regulatory transcription factors. In order to determine the role of Pax-2 during kidney development, we have generated a loss-of-function phenotype using antisense oligonucleotides in mouse kidney organ cultures. These oligonucleotides can specifically inhibit Pax-2 protein accumulation in kidney mesenchyme cells, where the intracellular concentrations are maximal. The kidney organ cultures were stained with uvomurulin and laminin antibodies as markers for epithelium formation. With significantly reduced Pax-2 protein levels, kidney mesenchyme cells fail to aggregate and do not undergo the sequential morphological changes characteristic of epithelial cell formation. The data demonstrate that Pax-2 function is required for the earliest phase of mesenchyme-to-epithelium conversion. C1 NICHHD,BETHESDA,MD 20892. NR 39 TC 220 Z9 224 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1993 VL 119 IS 3 BP 711 EP 720 PG 10 WC Developmental Biology SC Developmental Biology GA MH945 UT WOS:A1993MH94500013 PM 8187639 ER PT J AU DIMITROV, S ALMOUZNI, G DASSO, M WOLFFE, AP AF DIMITROV, S ALMOUZNI, G DASSO, M WOLFFE, AP TI CHROMATIN TRANSITIONS DURING EARLY XENOPUS EMBRYOGENESIS - CHANGES IN HISTONE-H4 ACETYLATION AND IN LINKER HISTONE TYPE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID 5S RNA GENE; URCHIN STRONGYLOCENTROTUS-PURPURATUS; TRANSCRIPTION FACTOR-IIIA; SEA-URCHIN; LAEVIS OOCYTES; DEVELOPMENTAL REGULATION; MOUSE DEVELOPMENT; SODIUM-BUTYRATE; MESSENGER-RNA; DNA RP DIMITROV, S (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM B1A-13,BETHESDA,MD 20892, USA. RI dimitrov, stefan/M-7697-2013; OI Dasso, Mary/0000-0002-5410-1371 NR 89 TC 169 Z9 173 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 NOV PY 1993 VL 160 IS 1 BP 214 EP 227 DI 10.1006/dbio.1993.1299 PG 14 WC Developmental Biology SC Developmental Biology GA MG581 UT WOS:A1993MG58100019 PM 8224538 ER PT J AU LAUDENSLAGER, ML RASMUSSEN, KLR BERMAN, CM SUOMI, SJ BERGER, CB AF LAUDENSLAGER, ML RASMUSSEN, KLR BERMAN, CM SUOMI, SJ BERGER, CB TI SPECIFIC ANTIBODY-LEVELS IN FREE-RANGING RHESUS-MONKEYS - RELATIONSHIPS TO PLASMA HORMONES, CARDIAC PARAMETERS, AND EARLY BEHAVIOR SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article ID MOTHER-INFANT SEPARATION; GROWTH-HORMONE; INDIVIDUAL-DIFFERENCES; STRESS; RESPONSES; PROLACTIN; MACAQUES; SEASON AB Levels of tetanus-specific antibodies were assessed in free-ranging, yearling rhesus monkeys following prophylactic immunization with tetanus toxoid. Each subject's behavior had been observed between 11 and 25 weeks of age and approximately 2 months later during its mother's first concentrated mating period as a part of another study. Prior to immunization, at approximately 1 year of age, cardiovascular parameters, and several plasma parameters [cortisol, adrenocorticotrophic hormone (ACTH), growth hormone (GH), interleukin-2 (IL-2), and total plasma immunoglobulin G (IgG)] were measured during a brief period of captivity. Antibody titers noted approximately 2 weeks after immunization were related to cardiovascular parameters. Thus, yearlings with high heart rates and low heart rate variability during captivity had the highest tetanus-specific serum IgG. Levels of plasma cortisol, ACTH, total IgG, and IL-2 noted at the time of capture were unrelated to subsequent antibody levels. Antibody titers were, however, positively correlated with GH noted immediately following capture on the day prior to immunization. Antibody titers were also related to the infants' behavior observed during their mother's first concentrated mating period. Infants who were most distressed (high levels of distress vocalization) when their mother resumed mating (a time particularly stressful for free-ranging rhesus infants) showed lower antibody titers to tetanus immunization as a yearling. The present observations add support to the existence of a relationship between behavior during exposure to an early stressor and later immune regulation and that certain cardiovascular parameters may be related to certain indicators of immunoregulation. (C) 1993 John Wiley & Sons, Inc. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD. SUNY BUFFALO,DEPT ANTHROPOL,BUFFALO,NY 14203. RP LAUDENSLAGER, ML (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,4455 E 12TH AVE,DENVER,CO 80220, USA. OI Laudenslager, Mark/0000-0002-9815-3026 FU NIMH NIH HHS [NIMH MH 37373] NR 37 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD NOV PY 1993 VL 26 IS 7 BP 407 EP 420 DI 10.1002/dev.420260704 PG 14 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA ME070 UT WOS:A1993ME07000003 PM 8270123 ER PT J AU HARRIS, M EASTMAN, R COWIE, C AF HARRIS, M EASTMAN, R COWIE, C TI SYMPTOMS OF SENSORY NEUROPATHY IN ADULTS WITH NIDDM IN THE UNITED-STATES POPULATION SO DIABETES CARE LA English DT Article ID NON-HISPANIC WHITES; DIABETES-MELLITUS; DEGENERATIVE COMPLICATIONS; MEXICAN-AMERICANS; EPIDEMIOLOGY AB OBJECTIVE- To ascertain the prevalence and determinants of sensory neuropathy symptoms through structured interview of a representative sample of people with diabetes in the U.S. population. RESEARCH DESIGN AND METHODS- The 1989 National Health Interview Survey consisted of a representative sample of 84,572 persons in the U.S. greater-than-or-equal-to 18 yr of age. A household respondent identified all people in the household believed to have diabetes (n = 2829). Subjects who could not be personally interviewed (n = 129) and individuals who stated they did not have diabetes (n = 295) were excluded. A detailed questionnaire was administered to 99.3% of the remaining 2405 subjects. Question's on symptoms of sensory neuropathy included whether during the past 3 mo the subjects had experienced numbness or loss of feeling, pain or tingling, or decreased ability to feel hot or cold. The neuropathy questions were also administered to a representative sample of 20,037 subjects who were not known to have diabetes. RESULTS- Prevalence of symptoms of sensory neuropathy was 30.2% among people with IDDM. This prevalence was 36.0% for men with NIDDM and 39.8% for women with NIDDM, compared with 9.8 and 11.8% for nondiabetic men and women, respectively. In logistic regression, factors independently related to symptoms of sensory neuropathy in people with NIDDM included duration of diabetes, hypertension, hyperglycemia, and glycosuria. Long duration of NIDDM (greater-than-or-equal-to 20 yr) was associated with a twofold increased risk of symptoms of sensory neuropathy compared with those with 0-4 yr of diabetes. Hypertension was associated with a 60% higher likelihood of symptoms. Diabetic individuals whose blood glucose was high all or most of the time or whose urine tests showed glucose all of the time were >2 times as likely to have symptoms of sensory neuropathy than those who did not report hyperglycemia or glycosuria. Age, sex, ethnicity, cigarette smoking, and height were not determinants of sensory neuropathy. CONCLUSIONS- Symptoms of sensory neuropathy affect 30-40% of diabetic patients in the U.S. Men and women are affected equally. Prevalence of these symptoms increases with longer duration of diabetes; hypertension and hyperglycemia predispose to symptoms of sensory neuropathy. C1 SOCIAL & SCI SYST, BETHESDA, MD USA. RP HARRIS, M (reprint author), NIDDK, WESTWOOD BLDG, ROOM 620, BETHESDA, MD 20892 USA. NR 27 TC 129 Z9 134 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1993 VL 16 IS 11 BP 1446 EP 1452 DI 10.2337/diacare.16.11.1446 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MD404 UT WOS:A1993MD40400004 PM 8299433 ER PT J AU BERGER, MS KOZAK, CA GABRIEL, A PRYSTOWSKY, MB AF BERGER, MS KOZAK, CA GABRIEL, A PRYSTOWSKY, MB TI THE GENE FOR C10, A MEMBER OF THE BETA-CHEMOKINE FAMILY, IS LOCATED ON MOUSE CHROMOSOME-11 AND CONTAINS A NOVEL 2ND EXON NOT FOUND IN OTHER CHEMOKINES SO DNA AND CELL BIOLOGY LA English DT Article ID MESSENGER-RNA PRECURSORS; GENOMIC STRUCTURE; CYTOKINE FAMILY; HUMAN HOMOLOG; PROTEIN; EXPRESSION; CONSERVATION; EVOLUTION; SEQUENCES; LD78 AB C10 is a recently described member of the beta-chemokine subfamily of the chemokine superfamily of cytokine proteins. Genomic clones encoding murine C10 were isolated and sequenced. The other members of the beta-chemokine family have a three-exon genomic structure containing, among other sequence similarities, four cysteines spaced in a highly conserved manner. In each of these genes, the second exon contains the first three of the four conserved cysteines, and the third exon contains the last. In contrast to this genomic structure, the C10 gene has four exons, with a novel second exon of 48 nucleotides. Exons 3 and 4 of C10 contain four cysteines distributed in the same manner as in exons 2 and 3 of other beta-chemokine family members. The novel second exon codes for a large number of charged amino acids, and this exon shows no homology to any previously described sequences in computer databases. Linkage studies showed that the C10 gene (Scya6) is closely linked to the Scya2 locus on mouse chromosome 11, indicating that the C10 gene is located in the same region of mouse chromosome 11 as other members of the beta-chemokine family. Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. HOSP UNIV PENN,DEPT PATHOL,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104. RP BERGER, MS (reprint author), VET ADM MED CTR,MED RES SERV 151,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA48648] NR 33 TC 24 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 1993 VL 12 IS 9 BP 839 EP 847 DI 10.1089/dna.1993.12.839 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA MH969 UT WOS:A1993MH96900010 PM 8216854 ER PT J AU NIKODIJEVIC, O JACOBSON, KA DALY, JW AF NIKODIJEVIC, O JACOBSON, KA DALY, JW TI ACUTE TREATMENT OF MICE WITH HIGH-DOSES OF CAFFEINE - AN ANIMAL-MODEL FOR CHOREIFORM MOVEMENT SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ADENOSINE RECEPTORS; XANTHINES; DOPAMINE; BEHAVIOR; LOCOMOTOR ACTIVITY ID BRAIN; ANTAGONISTS; IDPN; RAT AB Injection of caffeine at a dose of 35 to 70 mg/kg causes choreiform (dance-like) movements in NIH Swiss mice in a dose-dependent manner. The effect is less pronounced in mice that had chronically ingested caffeine for 7 days. The A(2a) selective adenosine agonist 2-[(2-amino-ethylamino)carbonylethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine (APEC), but not the A(1) selective agonist N-6-cyclohexyladenosine (CHA), diminished caffeine-elicited choreiform movement. The data suggest involvement of A(2a)-adenosine receptors in the appearance of choreiform movements. The dopamine antagonist haloperidol also reduced the chorea movements elicited by caffeine, but high doses were required. The calcium-channel blocker nitrendipine reduced the choreiform movements. These animals could provide a model for further investigation of the mechanisms underlying choreiform movements; as well as possible therapeutic approaches to certain choreas in humans related either to disease states (e.g., Huntington's disease or Tourette's syndrome) or to side effects of drug treatments. (C) 1993 Wiley-Liss, Inc. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 18 TC 8 Z9 8 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV PY 1993 VL 30 IS 3 BP 121 EP 128 DI 10.1002/ddr.430300304 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MP069 UT WOS:A1993MP06900003 ER PT J AU MIMURA, M BABA, T YAMAZAKI, H OHMORI, S INUI, Y GONZALEZ, FJ GUENGERICH, FP SHIMADA, T AF MIMURA, M BABA, T YAMAZAKI, H OHMORI, S INUI, Y GONZALEZ, FJ GUENGERICH, FP SHIMADA, T TI CHARACTERIZATION OF CYTOCHROME-P-450 2B6 IN HUMAN LIVER-MICROSOMES SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID TYPHIMURIUM STRAIN NM2009; RAT; ACTIVATION; SEQUENCE; ENZYMES; BIOACTIVATION; PURIFICATION; METABOLISM; OXIDATION; REDUCTASE AB A cytochrome P-450 (P-450) enzyme of the CYP2B subfamily was partially purified from human liver microsomes and characterized with respect to immunochemical properties, N-terminal amino acid sequence, and catalytic activities toward typical P-450 substrates. P-450 enzymes were monitored in chromatographic fractions by immunoblotting analysis using antibodies raised against a monkey P-450 2B, as well as several purified human P-450 enzymes. The final P-450 2B preparation thus obtained was contaminated with P450 3A4, but an N-terminal amino acid sequence matching the sequence predicted from the CYP2B6 cDNA was obtained. The apparent Mr of this protein was 48 kDa, and the migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was the same as that of the P-450 286 protein expressed in a human lymphoblast cell line. Immunoblotting analysis of 50 human liver samples revealed that the protein band considered to be P-450 2B6 was detected in only 12 samples, with four of these having relatively high levels. Several activities toward typical P-450 substrates were determined in a reconstituted monooxygenase system containing partially purified P-450 2B6 and compared with those obtained using a highly purified preparation of P-450 3A4 enzyme; we found that most of the activities were similar in these preparations, except that the partially purified P-460 2B6 showed high rates of activation of the mutagens 6-aminochrysene and 3-methoxy-4-aminoazobenzene to genotoxic metabolites in Salmonella typhimurium NM2009 strain. Antimonkey P-460 2B antibodies partially inhibited the activities toward these promutagens in liver microsomes of those human samples that contained relatively high levels of P-450 2B6. 6-Aminochrysene was also found to be converted to genotoxic metabolites by P-450 2B6 expressed in human lymphoblast cell lines; these activities were inhibited by antimonkey P-450 2B. All of these results collectively indicate that a P-450 2B protein is expressed in human liver and can be involved in monooxygenation reactions, including carcinogen activation, although the enzyme appears to be a rather minor P-450 constituent of most liver samples. C1 OSAKA PREFECTURAL INST PUBL HLTH,3-69 NAKAMICHI 1 CHOME,HIGASHINARI KU,OSAKA 537,JAPAN. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. CHIBA UNIV,FAC PHARMACEUT SCI,CHIBA,JAPAN. CTR ADULT DIS,OSAKA 537,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. OI Yamazaki, Hiroshi/0000-0002-1068-4261 FU NCI NIH HHS [CA 44353]; NIEHS NIH HHS [ES 00267] NR 34 TC 115 Z9 118 U1 0 U2 0 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 NOV-DEC PY 1993 VL 21 IS 6 BP 1048 EP 1056 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MJ393 UT WOS:A1993MJ39300011 PM 7905383 ER PT J AU ZHENG, W WINTER, SM MAYERSOHN, M BISHOP, JB SIPES, IG AF ZHENG, W WINTER, SM MAYERSOHN, M BISHOP, JB SIPES, IG TI TOXICOKINETICS OF SULFASALAZINE (SALICYLAZOSULFAPYRIDINE) AND ITS METABOLITES IN B6C3F(1) MICE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RHEUMATOID-ARTHRITIS; ACETYLATOR PHENOTYPE; CLINICAL PHARMACOKINETICS; ULCERATIVE-COLITIS; ADVERSE REACTIONS; SULPHASALAZINE; SULFAPYRIDINE; DRUG; ABSORPTION; TOXICITY AB The toxicokinetics of salicylazosulfapyridine (SASP) and its metabolites were investigated in male and female B6C3F1 mice either following single intravenous (5 mg/kg) or oral (67.5, 675, 1350, and 2700 mg/kg) doses, or following three consecutive daily oral doses (675, 1350, and 2700 mg/kg). Plasma concentrations of SASP and its metabolites were quantified by HPLC. Upon intravenous administration, SASP rapidly disappeared from blood with a mean residence time of 0.45-0.78 hr. The only metabolite of SASP found in plasma after an intravenous dose was sulfapyridine (SP). In both sexes, the absolute oral bioavailability of SASP ranged between 16.6-18.2% at a dose of 67.5 mg/kg, and between 2.6-8.7% at doses of 675-2700 mg/kg. Following oral administration of SASP, both SP and AcSP were identified in plasma. The area under the plasma concentration-time curves (AUC) of SP at all four oral doses were approximately 21- to 32-fold or 5- to 25-fold greater than those of SASP in male or female mice, respectively. The acetylated form of SP and AcSP, produced AUC values higher than SASP but much less than SP. Multiple oral doses with SASP did not alter the temporal patterns of SASP absorption and elimination in comparison to a single dose. However, SP accumulated in both sexes following multiple oral doses. A gender-dependent difference in toxicokinetic profiles for SASP and SP was also observed. Female mice displayed a higher C(max) of SASP and SP than did male mice. Although the volume of distribution of SASP was similar in both sexes, the systemic clearance of SASP in males was about twice that observed in females. The results indicated that after SASP administration, the metabolites SP and AcSP displayed higher and more prolonged plasma concentration-time profiles than parent SASP. Therefore, SP may accumulate in the body following repeated dosing and contribute to the genotoxicity observed following administration of high doses of SASP. C1 UNIV ARIZONA,COLL PHARM,DEPT PHARMACOL & TOXICOL,TUCSON,AZ. UNIV ARIZONA,DEPT PHARMACEUT SCI,TUCSON,AZ. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [N01-ES-85230] NR 32 TC 11 Z9 11 U1 0 U2 0 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 NOV-DEC PY 1993 VL 21 IS 6 BP 1091 EP 1097 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MJ393 UT WOS:A1993MJ39300017 PM 7905389 ER PT J AU WIRTH, PJ LUO, LD BENJAMIN, T HOANG, TN OLSON, AD PARMELEE, DC AF WIRTH, PJ LUO, LD BENJAMIN, T HOANG, TN OLSON, AD PARMELEE, DC TI THE RAT-LIVER EPITHELIAL (RLE) CELL NUCLEAR-PROTEIN DATABASE SO ELECTROPHORESIS LA English DT Article ID TUMOR SUPPRESSOR GENES; TRANSFORMING GROWTH FACTOR-BETA-1; MATRIX PROTEINS; 2-DIMENSIONAL ELECTROPHORESIS; TRANSCRIPTION FACTORS; GEL-ELECTROPHORESIS; COMPUTER-ANALYSIS; IDENTIFICATION; PROLIFERATION; POLYPEPTIDE AB The master two-dimensional computer database of rat liver epithelial (RLE) cellular proteins (Wirth et al., Electrophoresis 1991, 12, 931-954) has been expanded to include detailed information concerning 1100 nucleoplasmic (cytosolic) and 850 particulate associated [S-35]methionine labeled as well as 215 nucleoplasmic and 269 particulate associated [P-32]orthophosphate labeled RLE nuclear polypeptides, respectively. The RLE nuclear protein database developed using the Elsie 5 gel analysis system contains both qualitative and quantitative annotations including polypeptide identification number, protein name (if known), molecular weight and pI information, quantitation and polypeptide spot shape, subcellular location, as well as specific information regarding transformation (chemical and spontaneous) and growth-related characteristics. Microsequencing of polypeptides directly from two-dimensional (2-D) blotted membranes has recently been established in our laboratory and provides a highly efficient and rapid means of polypeptide identification in the absence of specific antibodies. At present the RLE protein database is still in the developmental stage and is continually being updated as additional information is obtained. Nonetheless, it is anticipated that knowledge obtained concerning the identification and characterization of specific transformation and/or growth regulatory proteins in the RLE in vitro cell system will not only have direct application to other rodent and human 2-D protein databases currently under development but will also complement them. RP WIRTH, PJ (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BIOPOLYMER CHEM SECT,BLDG 37 ROOM 3C28,BETHESDA,MD 20892, USA. NR 76 TC 12 Z9 13 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1993 VL 14 IS 11 BP 1199 EP 1215 DI 10.1002/elps.11501401180 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MN480 UT WOS:A1993MN48000003 PM 7508859 ER PT J AU FAVIT, A WETSEL, WC NEGROVILAR, A AF FAVIT, A WETSEL, WC NEGROVILAR, A TI DIFFERENTIAL EXPRESSION OF GAMMA-AMINOBUTYRIC-ACID RECEPTORS IN IMMORTALIZED LUTEINIZING-HORMONE-RELEASING HORMONE NEURONS SO ENDOCRINOLOGY LA English DT Article ID SUBUNIT MESSENGER-RNAS; GABA-A RECEPTOR; RAT-BRAIN; GLUTAMATE-DECARBOXYLASE; SECRETION; GNRH; HYPOTHALAMUS; MODULATION; PATTERNS; SYSTEMS AB Gamma-Aminobutyric acid (GABA) has been shown both to stimulate and inhibit LH secretion in vivo. GABA apparently exerts these effects at the hypothalamic level by regulating the release of LHRH. In this study, we have investigated the effect of GABAergic agents on LHRH secretion from an immortalized hypothalamic neuronal cell line (GT1-7). LHRH secretion was stimulated in a dose-dependent manner with increasing concentrations of GABA. This effect was mimicked by the GABA(A) receptor agonist, muscimol, and was blocked by the selective antagonist, bicuculline. The stimulatory effect of muscimol on LHRH secretion was synergistic with low concentrations of [K+]. By comparison, neither activation of the GABA(B) receptors with baclofen nor blockade with phaclofen influenced basal LHRH secretion. Baclofen, however, did depress [K+]-induced LHRH release. Binding studies confirmed the presence of GABA(A) and GABA(B) receptors on GT1-7 cells. In addition, Northern blots with probes to the GABA(A) receptor alpha1, beta3, and gamma2L subunits revealed that only the beta3 messenger RNA (MRNA) was expressed in the GT1-7 cells. These data provide the first demonstration that immortalized LHRH neurons are directly responsive to GABAergic agents. To the extent that these immortalized neurons may resemble those in vivo, our results suggest that GABAergic agents may play a dual role in reproductive physiology by exerting both stimulatory and inhibitory control over LHRH release. C1 NIEHS,CELLULAR & MOLEC LAB,HORMONE ACT GRP,POB 12233,BLDG 101,C4-107,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. NR 59 TC 52 Z9 52 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1993 VL 133 IS 5 BP 1983 EP 1989 DI 10.1210/en.133.5.1983 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME080 UT WOS:A1993ME08000010 PM 8404645 ER PT J AU SMITH, MS REINHART, J AF SMITH, MS REINHART, J TI CHANGES IN PITUITARY GONADOTROPIN-RELEASING-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID CONTENT DURING LACTATION AND AFTER PUP REMOVAL SO ENDOCRINOLOGY LA English DT Article ID PULSATILE LH-SECRETION; GNRH RECEPTORS; RAT; CELLS; EXPRESSION; CALCIUM AB Lactation is associated with a reduction in pituitary GnRH receptor content (GnRH-R) when compared with diestrus of the estrous cycle. These studies examined whether the changes in GnRH-R during lactation involved alterations in GnRH-R gene expression. GnRH-R messenger RNA (mRNA) levels were assessed by in situ hybridization, using a S-35-labeled antisense riboprobe coding for the transmembrane region of the mouse GnRH-R gene. The area occupied by grains in 20-mum sections of the pituitary was assessed with an image analysis program. The specificity of the probe for GnRH-R mRNA was demonstrated by the presence of only background grains over the pituitary when a sense riboprobe to GnRH-R mRNA was used. Also, there was an absence of clusters of grains over the posterior pituitary, an area devoid of gonadotropes. In lactating rats suckling eight pups on day 10 postpartum, GnRH-R mRNA levels in the anterior pituitary were suppressed by 60% when compared with the levels observed during diestrus. Removal of the eight-pup suckling stimulus for 24 h reestablished the diestrous pattern of GnRH-R mRNA expression. These results demonstrate that the suckling stimulus results in a significant suppression of GnRH-R mRNA levels that is reversed by removal of the stimulus. These changes in GnRH-R mRNA most likely contribute to the changes in GnRH-R content observed in response to the suckling stimulus. C1 NICHHD,ENDOCRINE & REPROD RES BRANCH,BETHESDA,MD 20892. RP SMITH, MS (reprint author), UNIV PITTSBURGH,SCH MED,DEPT NEUROBIOL,PITTSBURGH,PA 15261, USA. FU NICHD NIH HHS [HD-14643] NR 22 TC 22 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1993 VL 133 IS 5 BP 2080 EP 2084 DI 10.1210/en.133.5.2080 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME080 UT WOS:A1993ME08000022 PM 8404656 ER PT J AU WHITNALL, MH DRISCOLL, WJ LEE, YC STROTT, CA AF WHITNALL, MH DRISCOLL, WJ LEE, YC STROTT, CA TI ESTROGEN AND HYDROXYSTEROID SULFOTRANSFERASES IN GUINEA-PIG ADRENAL-CORTEX - CELLULAR AND SUBCELLULAR DISTRIBUTIONS SO ENDOCRINOLOGY LA English DT Article ID PREGNENOLONE-BINDING PROTEIN; INNER ZONES; POLYACRYLAMIDE GELS; SULFATE; CELLS; DEHYDROEPIANDROSTERONE; OUTER; LOCALIZATION; EXPRESSION; STEROIDS AB This report describes for the first time the cellular and subcellular localization of estrogen sulfotransferase (EST) as well as the subcellular localization of hydroxysteroid sulfotransferase (HST) in the mammalian adrenal cortex. A 34-kilodalton EST and two HSTs with 3alpha- and 3beta-hydroxysteroid substrate specificities (32 and 33 kilodaltons, respectively) were previously purified from guinea pig adrenal cortex and characterized. Western blots were used to establish that two antisera generated against EST were highly specific for EST, whereas three antisera generated against the HSTs were highly specific for the HSTs, but did not distinguish between the 3alpha- and 3betaHSTs. Light and electron microscopic immunoperoxidase labeling with these antisera revealed that the sulfotransferases were expressed only within the ACTH-responsive layers of the guinea pig adrenal cortex, with EST localized to zona fasciculata and zona reticularis cells, and the HSTs confined to the zona reticularis. No labeling was detected in the zona glomerulosa or adrenal medulla. EST was concentrated in cell nuclei; sparse labeling was distributed throughout the cytoplasm. HST labeling was intense in smooth endoplasmic reticulum of zona reticularis cells, hut was absent from nuclei. Ovoid inclusions about 14 mum in diameter, with no limiting membrane, were observed in zona reticularis cells; these inclusions were strongly labeled for both EST and HSTs. No gender-specific differences in distribution or labeling intensity were apparent. The high concentration of EST immunoreactivity in nuclei suggests that EST may play a role in modulating the ability of active estrogens to regulate gene expression in ACTH-responsive cells. The distribution of HST labeling suggests that sulfonation of adrenocortical 3-hydroxysteroids takes place largely within smooth endoplasmic reticulum in the zona reticularis in adult guinea pigs. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,ADRENAL CELL BIOL SECT,BETHESDA,MD 20892. RP WHITNALL, MH (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT PHYSIOL,BETHESDA,MD 20889, USA. NR 38 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 NOV PY 1993 VL 133 IS 5 BP 2284 EP 2291 DI 10.1210/en.133.5.2284 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME080 UT WOS:A1993ME08000049 PM 8404682 ER PT J AU KOKIA, E HURWITZ, A BENSHLOMO, I ADASHI, EY YANAGISHITA, M AF KOKIA, E HURWITZ, A BENSHLOMO, I ADASHI, EY YANAGISHITA, M TI RECEPTOR-MEDIATED STIMULATORY EFFECT OF IL-1-BETA ON HYALURONIC-ACID AND PROTEOGLYCAN BIOSYNTHESIS BY CULTURED RAT OVARIAN-CELLS - ROLE FOR HETEROLOGOUS CELL-CELL INTERACTIONS SO ENDOCRINOLOGY LA English DT Article ID GRANULOSA-CELLS; INTERLEUKIN-1; INVITRO AB An increasing body of information supports the possibility that intraovarian interleukin (IL)-1 may play an intermediary role in gonadotropin-triggered ovulation. To further evaluate this hypothesis, we have examined the effect of IL-1beta on ovarian proteoglycan/glycosaminoglycan economy, an established corollary of the preovulatory cascade. Rat ovarian cells were metabolically labeled with [S-35]sulfate and [H-3]glucosamine for 48h in the absence or presence of IL-1beta, with or without an IL-1 receptor antagonist (IL-1ra). At the conclusion of this treatment period, total S-35 and H-3 incorporation into cell-associated and extracellular proteoglycan/ glycosaminoglycan species was determined. Treatment of whole ovarian dispersates with IL-1beta (10ng/ml) produced substantial increments in the accumulation of extracellular macromolecular material [ 1 1.5-, 2.9- and 2.6-fold for hyaluronic acid (HA), heparan sulfate (HS) and dermatan sulfate (DS) proteoglycans, respectively]. In contrast, only modest increments (less-than-or-equal-to 1.7-fold) were noted for IL-1beta-treated granulosa cells (GC), theca-interstitial cells (TC), or 4:1 co-cultures (GC/TC) thereof. Treatment of whole ovarian dispersates with IL-1beta also resulted in significant (P<0.001) increments in the cell-associated accumulation of both HA (6.0-fold increase) and DS proteoglycans (3.4-fold increase). However, the cell-associated accumulation of HS proteoglycan was not significantly affected by IL-1beta regardless of the cellular preparation under study. The concurrent provision of IL-Ira (5mug/ml) all but neutralized the IL-1beta effect on HA biosynthesis thereby suggesting mediation by specific ovarian IL-1 receptor(s). Taken together, these observations suggest that treatment of ovarian cells with IL-1beta results in an overall increase in macromolecular biosynthesis as well as in redistribution favoring extracellular HA and DS (but not HS) proteoglycans. Moreover, since whole ovarian dispersates proved more responsive to IL-1 than isolated cellular components thereof, the present observations suggest an obligatory requirement for heterologous cell-cell interaction without which optimal HA or proteoglycan biosynthesis may not be realized. These observations along with the demonstration of IL-1-mediated amplification of gonadotropin-triggered ovulation provide strong indirect support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of C1 UNIV MARYLAND,SCH MED,DEPT PHYSIOL,DIV REPROD ENDOCRINOL,BALTIMORE,MD 21201. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 17 TC 42 Z9 42 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 NOV PY 1993 VL 133 IS 5 BP 2391 EP 2394 DI 10.1210/en.133.5.2391 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME080 UT WOS:A1993ME08000062 PM 8404691 ER PT J AU MORETTO, M LOPEZ, FJ NEGROVILAR, A AF MORETTO, M LOPEZ, FJ NEGROVILAR, A TI NITRIC-OXIDE REGULATES LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETION SO ENDOCRINOLOGY LA English DT Article ID EXCITATORY AMINO-ACIDS; CYCLIC-GMP; NERVOUS-SYSTEM; GLUTAMATE; NO; CEREBELLUM; HEMOGLOBIN; MESSENGER; ARGININE; PROTEIN AB We have analyzed the role of nitric oxide (NO), an unorthodox and novel neuromodulator, on luteinizing hormone-releasing hormone (LHRH) secretion. Sodium nitroprusside (SNP), an NO donor, was used to challenge LHRH neurons using both hypothalamic explants and an immortalized neuronal cell line (GTI cells) in vitro. In both paradigms, SNPwas able to stimulate LHRH release in a dose-dependent manner. This action of SNP was accompanied by an elevation in both extra- and intra-cellular cGMP levels. In addition, exposure of LHRH cells (GTI -7 cells) to increasing concentrations of a soluble analog of cGMP (8-Br-cGMP) enhanced LHRH release in a dose-dependent manner, indicating that LHRH neurons have the intrinsic ability to respond to the intracellular messenger elicited by NO,i.e.,cGMP. Furthermore, sodium nitroprusside-induced LHRH secretion from GTI-7 cells was blocked, in a dose-dependent manner, by Rp-8-Br-cGMPS, a cGMP analog which blocks cGMP-dependent protein kinase. These data clearly demonstrate that NO stimulates LHRH secretion by activating guanylate cyclase, and support a potential role of NO as a neuroactive agent involved in the control of LHRH secretion and, thereby, reproductive functions. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. NR 36 TC 213 Z9 219 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1993 VL 133 IS 5 BP 2399 EP 2402 DI 10.1210/en.133.5.2399 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME080 UT WOS:A1993ME08000064 PM 8104781 ER PT J AU GREENWALD, P KELLOFF, G KALAGHER, S MCDONALD, S AF GREENWALD, P KELLOFF, G KALAGHER, S MCDONALD, S TI RESEARCH STUDIES ON CHEMOPREVENTION OF ESOPHAGEAL CANCER AT THE UNITED-STATES NATIONAL-CANCER-INSTITUTE SO ENDOSCOPY LA English DT Article; Proceedings Paper CT International Congress on Cancer of the Esophagus CY JUN, 1992 CL GENOA, ITALY SP GRP OPERAT STUDIO PRECANCEROSI ESOFAGO ID SQUAMOUS-CELL CARCINOMA; INTERMEDIATE END-POINTS; 13-CIS-RETINOIC ACID; BETA-CAROTENE; GROWTH-FACTOR; VITAMIN-A; EPIDEMIOLOGY; PREVENTION; CARCINOGENESIS; HEAD C1 PROPECT ASSOCIATES,ROCKVILLE,MD. RP GREENWALD, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 79 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD NOV PY 1993 VL 25 IS 9 BP 617 EP 626 DI 10.1055/s-2007-1010417 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA MM687 UT WOS:A1993MM68700014 PM 8119217 ER PT J AU SUK, W ANDERSON, B AF SUK, W ANDERSON, B TI SUPERFUND CONFERENCES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP SUK, W (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1993 VL 101 IS 6 BP 538 EP 539 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MJ957 UT WOS:A1993MJ95700012 ER PT J AU SHYR, LJ SABOURIN, PJ MEDINSKY, MA BIRNBAUM, LS HENDERSON, RF AF SHYR, LJ SABOURIN, PJ MEDINSKY, MA BIRNBAUM, LS HENDERSON, RF TI PHYSIOLOGICALLY-BASED MODELING OF 2-BUTOXYETHANOL DISPOSITION IN RATS FOLLOWING DIFFERENT ROUTES OF EXPOSURE SO ENVIRONMENTAL RESEARCH LA English DT Article ID GLYCOL MONOBUTYL ETHER; ETHYLENE-GLYCOL; INHALED 2-BUTOXYETHANOL; METABOLISM; BUTOXYETHANOL; ELIMINATION; TOXICOKINETICS; TOXICITY C1 NIEHS,RES TRIANGLE PK,NC 27709. RP SHYR, LJ (reprint author), LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,POB 5890,ALBUQUERQUE,NM 87185, USA. FU NIEHS NIH HHS [NIEHS 222-ES-20092] NR 29 TC 10 Z9 12 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 1993 VL 63 IS 2 BP 202 EP 218 DI 10.1006/enrs.1993.1141 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA MG341 UT WOS:A1993MG34100004 PM 8243415 ER PT J AU SWANSON, CA WILBANKS, GD TWIGGS, LB MORTEL, R BERMAN, ML BARRETT, RJ BRINTON, LA AF SWANSON, CA WILBANKS, GD TWIGGS, LB MORTEL, R BERMAN, ML BARRETT, RJ BRINTON, LA TI MODERATE ALCOHOL-CONSUMPTION AND THE RISK OF ENDOMETRIAL CANCER SO EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; ENDOMETRIAL NEOPLASMS; SMOKING; MENOPAUSE; ORAL CONTRACEPTIVES; EXERCISE; PARITY; DIETARY FAT; CASE-CONTROL STUDY AB In a multicenter case-control study that included 400 cases and 297 controls, we examined the relation of moderate alcohol consumption to risk of endometrial cancer. We estimated average weekly intake of alcohol during adulthood from the reported frequency of intake of beer, wine, and liquor. The relative risk of endometrial cancer was 0.82 (95% confidence interval = 0.6-1.2) among women who drank, compared with lifelong abstainers. The weak protective effect of alcohol was due to a stronger inverse association among young women (<55 years). In young women, the age-adjusted relative risks for three levels of drinking (<1, 1-4, >4 drinks per week), from lowest to highest, were 0.78, 0.64, and 0.41 compared with nondrinkers. The risk estimates were not materially altered after adjustment for a variety of factors related to alcohol intake and to low risk of the disease (for example, smoking, oral contraceptive use, low body mass index, increased physical activity). The protective effect of alcohol could not be attributed to one particular type of alcohol-containing beverage, but beer appeared to have the most pronounced effect. These results suggest an inverse association between moderate alcohol consumption and endometrial cancer risk among young women, but support for a causal association is qualified and requires confirmation. RP SWANSON, CA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN SUITE 430,ROCKVILLE,MD 20852, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 35 Z9 36 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1993 VL 4 IS 6 BP 530 EP 536 DI 10.1097/00001648-199311000-00009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ME752 UT WOS:A1993ME75200009 PM 8268282 ER PT J AU LISSEN, E ALTER, HJ ABAD, MA TORRES, Y PEREZROMERO, M LEAL, M PINEDA, JA TORRONTERAS, R SANCHEZQUIJANO, A AF LISSEN, E ALTER, HJ ABAD, MA TORRES, Y PEREZROMERO, M LEAL, M PINEDA, JA TORRONTERAS, R SANCHEZQUIJANO, A TI HEPATITIS-C VIRUS-INFECTION AMONG SEXUALLY PROMISCUOUS GROUPS AND THE HETEROSEXUAL PARTNERS OF HEPATITIS-C VIRUS-INFECTED INDEX CASES SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID NON-B-HEPATITIS; NON-A; TRANSMISSION; RISK; CONTACT; SPAIN; HIV AB To define the role of sexual transmission in the spread of hepatitis C virus (HCV) infection, a seroprevalence study of antibodies against HCV was performed in populations at high risk for sexually transmitted diseases. Subjects included 310 female prostitutes, 88 clients of prostitutes, 168 homosexual men and 147 stable heterosexual partners of index cases reactive for anti-HCV (98 of whom were partners of drug addicts coinfected with HCV and human inmunodeficiency virus [HTV]). All subjects denied prior transfusion or intravenous drug use. Controls were 400 voluntary blood donors selected randomly from first-time donors. The prevalence of anti-HCV by enzyme immunoassay, confirmed by a second-generation recombinant immunoblot assay, was 6.4% in prostitutes, 6.8% in clients of prostitutes, 4.2% in homosexual men, 7.4% in heterosexual partners of index cases and 1.2% in random donors. However, the anti-HCV prevalence in stable heterosexual partners of HCV-positive/HIV-positive index cases was 2.2 times higher than in stable heterosexual partners of index cases reactive for anti-HCV only (9.2% vs. 4.1%), and sexual partners of index cases coinfected with HCV and HIV were almost three times more likely to be infected with HIV than with HCV (25.5% vs. 9.2%). These data suggest that HCV infection may be sexually transmitted but with low efficiency and that this efficiency could be increased in the presence of coexistent HIV infection in the index case. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP LISSEN, E (reprint author), VIRGEN DEL ROCIO UNIV HOSP,VIRAL HEPATITIS & AIDS STUDY GRP,AV MANUEL SIUROT S-N,E-41013 SEVILLE,SPAIN. RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015; IBIS, INFECCIOSAS HU/C-1271-2016; OI Pineda, Juan A./0000-0002-3751-0296 NR 22 TC 52 Z9 53 U1 0 U2 1 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD NOV PY 1993 VL 12 IS 11 BP 827 EP 831 DI 10.1007/BF02000402 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA MM849 UT WOS:A1993MM84900003 PM 7509282 ER PT J AU ESCHWEILER, GW RAUSCHECKER, JP AF ESCHWEILER, GW RAUSCHECKER, JP TI TEMPORAL INTEGRATION IN VISUAL-CORTEX OF CATS WITH SURGICALLY INDUCED STRABISMUS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE AMBLYOPIA; SQUINT; LATENCY; FLASH RESPONSE; TIMING ID RECEPTIVE-FIELD PROPERTIES; RETINAL GANGLION-CELLS; STRIATE CORTEX; CONVERGENT STRABISMUS; DIVERGENT STRABISMUS; HEBB SYNAPSES; KITTENS; AMBLYOPIA; NEURONS; CONNECTIONS AB Single unit response latencies in striate cortex after visual stimulation with stationary flashed bars were measured and interocularly compared in anaesthetized cats with surgically induced strabismus, in order to elucidate the neural basis of strabismic amblyopia. Four unilateral esotropic and two exotropic cats were studied. The visual onset latencies of cortical neurons ranged from 30 to 170 ms after stimulation of the non-deviating eye at a contrast of 82%. Responses after visual stimulation of the deviating eye were consistently delayed by approximately 10 ms. The latency increase was independent of the direction and absolute angle of squint in the different animals. Peak latencies of cortical neurons ranged from 43 to 245 ms. Median peak latency was 85 ms for the non-deviating and 95 ms for the deviating eye. The rise time of cortical flash responses, as determined from onset - peak differences, ranged between 2 and 170 ms. Direct interocular comparison of response latencies in the remaining binocular neurons revealed an invariable advantage for the non-deviating eye. Supragranular neurons showed a greater interocular latency difference than neurons in layer IV. Visual latencies were contrast-dependent. However, the latency reduction with increasing contrast was less pronounced for the deviating eye. We discuss the possibility that central integration times, especially within cortex, are prolonged in strabismic cats, affecting temporal coincidence of signal processing in the visual cortex. The resulting disturbance of spatio-temporal integration, as caused by a scrambling of geniculo-striate and intracortical connections, may be the substrate of binocular suppression and strabismic amblyopia. C1 NIMH, NEUROPHYSIOL LAB, POB 608, POOLESVILLE, MD 20837 USA. MAX PLANCK INST BIOL KYBERNET, W-7400 TUBINGEN, GERMANY. RI Rauschecker, Josef/A-4120-2013 NR 48 TC 15 Z9 15 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV 1 PY 1993 VL 5 IS 11 BP 1501 EP 1509 DI 10.1111/j.1460-9568.1993.tb00218.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA MF956 UT WOS:A1993MF95600010 PM 7506973 ER PT J AU CORWIN, RL ROBINSON, JK CRAWLEY, JN AF CORWIN, RL ROBINSON, JK CRAWLEY, JN TI GALANIN ANTAGONISTS BLOCK GALANIN-INDUCED FEEDING IN THE HYPOTHALAMUS AND AMYGDALA OF THE RAT SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ANTAGONISTS; CENTRAL NUCLEUS OF THE AMYGDALA; FOOD CONSUMPTION; NEUROPEPTIDE; PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS; RECEPTOR ID CENTRAL NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; NEUROPEPTIDE-Y; CHIMERIC PEPTIDE; RECEPTOR-BINDING; IMMUNOREACTIVITY; STIMULATION; LOCALIZATION; FRAGMENTS; LIGANDS AB Galanin significantly increased food intake when microinjected into the region of the central nucleus of the amygdala as well as into the paraventricular nucleus of the hypothalamus. In the amygdala this effect was specific to feeding; no change in grooming, resting, or other behaviour was observed after galanin treatment. These results provide evidence that the amygdala may be an important site in the mediation of galanin-induced feeding. The galanin receptor antagonists, C7 and M40, antagonized galanin-induced feeding, while having no effect alone on food consumption in free-feeding rats. These new galanin receptor antagonists provide useful tools for further investigating the role of endogenous galanin in the regulation of feeding. RP CORWIN, RL (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 41 TC 111 Z9 112 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV 1 PY 1993 VL 5 IS 11 BP 1528 EP 1533 DI 10.1111/j.1460-9568.1993.tb00221.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA MF956 UT WOS:A1993MF95600013 PM 7506975 ER PT J AU LI, Q LOPEZ, JS CASPI, RR ROBERGE, FG NUSSENBLATT, RB KADOR, PF CHAN, CC AF LI, Q LOPEZ, JS CASPI, RR ROBERGE, FG NUSSENBLATT, RB KADOR, PF CHAN, CC TI SUPPRESSION OF S-ANTIGEN-INDUCED EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN LEWIS RATS BY ORAL-ADMINISTRATION WITH CGS-13080, A THROMBOXANE SYNTHETASE INHIBITOR SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); S-ANTIGEN; CGS-13080; THROMBOXANE SYNTHETASE INHIBITOR; IMMUNE RESPONSE; PROSTAGLANDINS ID UVEITIS; ACID; INTERLEUKIN-2; ASSOCIATION; CELLS C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NR 26 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 1993 VL 57 IS 5 BP 601 EP 608 DI 10.1006/exer.1993.1165 PG 8 WC Ophthalmology SC Ophthalmology GA MH686 UT WOS:A1993MH68600010 PM 8282047 ER PT J AU TATELMAN, HM TALAN, MI AF TATELMAN, HM TALAN, MI TI METABOLIC HEAT-PRODUCTION AND COLD TOLERANCE DURING COLD STRESS OF DIFFERENT INTENSITY OF ADULT AND AGED MALE C57BL/6J MICE SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE THERMOREGULATION; AGE; MICE; COLD STRESS ID BROWN-ADIPOSE-TISSUE; YOUNG; RATS; OLD; THERMOREGULATION; MITOCHONDRIA; RESPONSES; T3 AB Adult and aged male C57BL/6J mice were subjected to a 3-h cold stress test at either 24-degrees-C, 18-degrees-C, 12-degrees-C, or 6-degrees-C. Body mass was measured before the test, and colonic temperature, O2 consumption, and CO2 production were measured during the test. The slopes of colonic temperature over time of test and the mean metabolic heat production were calculated for each animal. While adult mice had a relatively small reduction in colonic temperature during the test at all four ambient temperatures, in the aged mice ambient temperatures resulted in steeper reductions of colonic temperature. In adult mice, an increase in metabolic heat production was proportional to ambient cold. The thermogenic response of aged mice at 24-degrees-C and at 18-degrees-C was similar to adult mice, suggesting that the ability of aged mice to respond to cold by increasing heat production does not diminish with age. However, in aged mice metabolic heat production at 12-degrees-C and 6-degrees-C was significantly below that of adult mice, which indicated a reduced capacity for thermogenesis. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 22 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 1993 VL 28 IS 6 BP 579 EP 584 DI 10.1016/0531-5565(93)90047-H PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MK143 UT WOS:A1993MK14300009 PM 8137894 ER PT J AU VENER, KJ FEUER, EJ GORELIC, L AF VENER, KJ FEUER, EJ GORELIC, L TI A STATISTICAL-MODEL VALIDATING TRIAGE FOR THE PEER-REVIEW PROCESS - KEEPING THE COMPETITIVE APPLICATIONS IN THE REVIEW PIPELINE SO FASEB JOURNAL LA English DT Article DE GRANT REVIEW; NATIONAL INSTITUTES OF HEALTH; STATISTICAL MODEL; APPLICATION TRIAGE AB Triage of grant application at the National Institutes of Health (NIH) is a process whereby an initial screening of applications by a scientific peer review group eliminates applications that are not competitive for awards. The process of application triage has been limited to those applications submitted to the NIH in response to an RFA (Request for Applications). A hypergeometric model was developed to determine the extent to which five, six, seven, or eight member triage teams or subsets of 12-to-20 member full committees could provide a statistically defensible triage decision. Although the intent of triage is to remove from review those applications that are noncompetitive, the model was weighted in favor of the applicant to minimize the likelihood that highly competitive applications would be eliminated. Within the assumptions and rules developed, it was determined that there was little likelihood that the latter would occur. For example, in the worst case scenario, the greatest probability that a highly competitive application would be knocked out of competition is P less-than-or-equal-to 0.014 in the case of a five-member triage subset of a 20-member committee. Using the latter case, the model was tested on a set of 73 applications that were submitted to the National Cancer Institute for action at the February 1993 National Cancer Advisory Board. The model selected for triage required that each application be assigned to five reviewers, that each reviewer be blinded to the review assignments of the other reviewers, and that four noncompetitive votes be registered to triage out an application. Each of 19 applications received four to five noncompetitive votes, and were triaged out of the review process. The remaining 54 applications were then reviewed according to the usual NIH review process. Four of the applications received three noncompetitive triage votes each and were either rated as not recommended for further consideration (NRF, n=2)) or received priority scores greater-than-or-equal-to 250 (n=2) (The smaller the priority score the better the technical merit). Thirteen of the 53 applications received two noncompetitive votes. Of the latter, two were not recommended for further consideration and the remaining 11 received priority scores between in excess of 200. The distribution of competitive applications was such that funding was limited to those applications with priority scores of less than 190. Thus, the data suggest that the conservative model is valid such that the likelihood of eliminating a highly competitive application from consideration for funding is remotely small. With this model, the process of triage is fair to applicants on the one hand and is also effective in reducing consultant workloads on the other. The model could be applied to many different types of review situations (private sponsors as well as federal), especially when few awards are to be issued relative to the number of competing applications. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP VENER, KJ (reprint author), NCI,PREVENT EPIDEMIOL & CONTROL REVIEW SECT,BETHESDA,MD 20892, USA. NR 3 TC 9 Z9 9 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 NOV PY 1993 VL 7 IS 14 BP 1312 EP 1319 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA MH008 UT WOS:A1993MH00800002 PM 8224604 ER PT J AU ZHOU, J BONDY, C AF ZHOU, J BONDY, C TI ANATOMY OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN THE HUMAN TESTIS SO FERTILITY AND STERILITY LA English DT Article DE IGF RECEPTOR; IGF BINDING PROTEIN; SEMINIFEROUS TUBULES; SPERMATOGENESIS; LEYDIG CELL; MESSENGER RNA; IN-SITU HYBRIDIZATION ID MESSENGER-RIBONUCLEIC-ACID; FACTOR BINDING-PROTEIN; FACTOR-I RECEPTOR; EXPRESSION; RAT; CELLS; SECRETION; FOLLICLE; CLONING AB Objective: To study the cellular patterns of gene expression for insulin-like growth factors I and II (IGF-I and IGF-II), their receptors and specific high-affinity binding proteins (IGFBPs) in the human testis. Design: In situ hybridization histochemistry was used to localize messenger ribonucleic acids (mRNAs) for IGF-I and IGF-II, the IGF-I and IGF-II receptors and IGFBP-1 to 6 in fresh-frozen testis sections from healthy young men who died of trauma. Results: Insulin-like growth factor I mRNA was not detected. Insulin-like growth factors II mRNA was abundant in testicular blood vessels and peritubular connective tissue. Both IGF-I and IGF-II receptor mRNAs were most abundant in the germinal epithelium. Insulin-like growth factor binding protein 1 mRNA was not detected. Binding protein-2 mRNA was expressed in both Leydig and Sertoli cells. Binding protein-3 mRNA was detected only in the endothelium of testicular blood vessels. Binding protein-4 mRNA was also localized in endothelium but, in addition, was present in Leydig cells and interstitial connective tissue. Binding protein-5 mRNA was abundant in connective tissue and was detected at low levels in Leydig cells. Binding protein-6 mRNA was present in some of the peritubular cells and in some cells of the interstitial compartment. Conclusion: Our results suggest that IGFs may play significant roles in testicular function and germ cell development. RP ZHOU, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 24 TC 58 Z9 58 U1 0 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 1993 VL 60 IS 5 BP 897 EP 904 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ME311 UT WOS:A1993ME31100027 PM 7693517 ER PT J AU STARKEREED, PE OLIVER, CN CARNEY, JM STADTMAN, ER AF STARKEREED, PE OLIVER, CN CARNEY, JM STADTMAN, ER TI MODIFICATION OF PROTEINS DURING OXIDATIVE STRESS AND AGING SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. MERCK SHARP & DOHME LTD,W POINT,PA 19486. UNIV KENTUCKY,LEXINGTON,KY 40536. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 479 EP 479 DI 10.1016/0891-5849(93)90215-G PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700031 ER PT J AU MASON, RP HANNA, PM KADIISKA, MB AF MASON, RP HANNA, PM KADIISKA, MB TI IN-VIVO ESR SPIN-TRAPPING EVIDENCE FOR HYDROXYL RADICAL-MEDIATED TOXICITY OF PARAQUAT AND COPPER IN RATS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 1 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 480 EP 480 DI 10.1016/0891-5849(93)90221-F PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700036 ER PT J AU KADIISKA, MB HANNA, PM JORDAN, SJ MASON, RP AF KADIISKA, MB HANNA, PM JORDAN, SJ MASON, RP TI IN-VIVO EVIDENCE FOR FREE-RADICAL GENERATION IN SELENIUM-DEFICIENT AND VITAMIN-E-DEFICIENT RATS DURING ACUTE COPPER OVERLOAD - AN ESR SPIN-TRAPPING INVESTIGATION SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 483 EP 483 DI 10.1016/0891-5849(93)90232-J PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700046 ER PT J AU SHACTER, E WILLIAMS, JA LEVINE, RL AF SHACTER, E WILLIAMS, JA LEVINE, RL TI DIFFERENTIAL SUSCEPTIBILITY OF PLASMA-PROTEINS TO OXIDATION - EXAMINATION BY WESTERN-BLOT IMMUNOASSAY SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 483 EP 483 DI 10.1016/0891-5849(93)90231-I PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700047 ER PT J AU HANNA, PM KADIISKA, MB JORDAN, SJ MASON, RP AF HANNA, PM KADIISKA, MB JORDAN, SJ MASON, RP TI THE EFFECT OF ZINC(II) AND CHROMIUM(III) ON CARBON-TETRACHLORIDE HEPATOTOXICITY - EVIDENCE AGAINST TRICHLOROMETHYL RADICAL SCAVENGING BY METALLOTHIONEIN IN-VIVO SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 492 EP 492 DI 10.1016/0891-5849(93)90265-V PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700080 ER PT J AU CHAMULITRAT, W PARKER, CE TOMER, KB MASON, RP AF CHAMULITRAT, W PARKER, CE TOMER, KB MASON, RP TI PHENYL N-TERT-BUTYLNITRONE (PBN) AS A PRECURSOR OF NITROGEN-OXIDES RESULTING FROM IRON (III)-CATALYZED HYDROLYSIS AND HYDROXYL RADICAL ADDUCT FORMATION SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 499 EP 499 DI 10.1016/0891-5849(93)90294-5 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700109 ER PT J AU CIOLINO, HP LEVINE, RL AF CIOLINO, HP LEVINE, RL TI PROTEIN OXIDATION IS AN EARLY EVENT IN OXIDANT INJURY TO ENDOTHELIAL-CELLS IN-VITRO SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 519 EP 519 DI 10.1016/0891-5849(93)90367-4 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700183 ER PT J AU CHAMULITRAT, W JORDAN, SJ MASON, RP SAITO, K CUTLER, RG AF CHAMULITRAT, W JORDAN, SJ MASON, RP SAITO, K CUTLER, RG TI NITRIC-OXIDE FORMATION DURING LIGHT-INDUCED DECOMPOSITION OF PHENYL N-TERT-BUTYLNITRONE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 529 EP 529 DI 10.1016/0891-5849(93)90406-K PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700221 ER PT J AU ANDERSON, WB KARASZKIEWICZ, JW AHN, C LEE, SA AF ANDERSON, WB KARASZKIEWICZ, JW AHN, C LEE, SA TI DIFFERENTIAL SUSCEPTIBILITY OF PROTEIN-KINASE-C TO OXIDATIVE INACTIVATION AND SUBSEQUENT DOWN-REGULATION IN DRUG-SENSITIVE AND MULTIDRUG-RESISTANT MCF-7 HUMAN BREAST-CARCINOMA CELLS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 541 EP 541 DI 10.1016/0891-5849(93)90448-4 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700263 ER PT J AU GOLDMAN, R STOYANOVSKY, D TSYRLOV, I GROGAN, J KAGAN, V AF GOLDMAN, R STOYANOVSKY, D TSYRLOV, I GROGAN, J KAGAN, V TI REDUCTION OF PHENOXYL RADICALS BY THE PURIFIED HUMAN NADPH CYTOCHROME-P-450 REDUCTASE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI,LMC,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. OI Stoyanovsky, Detcho/0000-0001-5591-4780 NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 542 EP 542 DI 10.1016/0891-5849(93)90453-2 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700268 ER PT J AU HOLBROOK, NJ LUETHY, JD CHOI, AMK AF HOLBROOK, NJ LUETHY, JD CHOI, AMK TI REGULATION OF GENE-EXPRESSION IN OXIDATIVE STRESS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1993 VL 15 IS 5 BP 543 EP 543 DI 10.1016/0891-5849(93)90454-3 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MD267 UT WOS:A1993MD26700269 ER PT J AU CHHABRA, RS BUCHER, JR HASEMAN, JK ELWELL, MR KURTZ, PJ CARLTON, BD AF CHHABRA, RS BUCHER, JR HASEMAN, JK ELWELL, MR KURTZ, PJ CARLTON, BD TI COMPARATIVE CARCINOGENICITY OF POLYBROMINATED BIPHENYLS WITH OR WITHOUT PERINATAL EXPOSURE IN RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID CHILDHOOD-CANCER; LIVER-TUMORS; PARENTS; PBB; TOXICOLOGY; MORTALITY; INDUCTION; CHEMICALS; SMOKING C1 BATTELLE MEM INST,COLUMBUS,OH 43201. RP CHHABRA, RS (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 15 Z9 16 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1993 VL 21 IS 4 BP 451 EP 460 DI 10.1006/faat.1993.1121 PG 10 WC Toxicology SC Toxicology GA MG174 UT WOS:A1993MG17400007 PM 8253298 ER PT J AU HEBERT, CD ELWELL, MR TRAVLOS, GS FITZ, CJ BUCHER, JR AF HEBERT, CD ELWELL, MR TRAVLOS, GS FITZ, CJ BUCHER, JR TI SUBCHRONIC TOXICITY OF CUPRIC SULFATE ADMINISTERED IN DRINKING-WATER AND FEED TO RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; COPPER TOXICOSIS; DIETARY COPPER; LIVER; KIDNEY; TOLERANCE C1 NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. BIOTECH SERV INC,N LITTLE ROCK,AR 72116. RP HEBERT, CD (reprint author), NIEHS,TOXICOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 35 Z9 36 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1993 VL 21 IS 4 BP 461 EP 475 DI 10.1006/faat.1993.1122 PG 15 WC Toxicology SC Toxicology GA MG174 UT WOS:A1993MG17400008 PM 8253299 ER PT J AU HONG, HL BOORMAN, GA AF HONG, HL BOORMAN, GA TI RESIDUAL MYELOTOXICITY OF LINDANE IN MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID BONE-MARROW; STEM-CELLS; PROGENITOR CELLS; APLASTIC-ANEMIA; GAMMA-HCH; DAMAGE; MOUSE; ERYTHROPOIESIS; ORGANOCHLORINE; BUSULFAN RP HONG, HL (reprint author), NIEHS,NATL TOXICOL PROGRAM,PATHOL BRANCH,MD D2-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 62 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1993 VL 21 IS 4 BP 500 EP 507 DI 10.1006/faat.1993.1126 PG 8 WC Toxicology SC Toxicology GA MG174 UT WOS:A1993MG17400012 PM 7504641 ER PT J AU LANG, DS MEIER, KL LUSTER, MI AF LANG, DS MEIER, KL LUSTER, MI TI COMPARATIVE EFFECTS OF IMMUNOTOXIC CHEMICALS ON IN-VITRO PROLIFERATIVE RESPONSES OF HUMAN AND RODENT LYMPHOCYTES SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID MEMORY T-CELLS; T-2 TOXIN; CYCLOSPORINE-A; EXPOSURE; LEAD; ACTIVATION; MICE; SENSITIVITY; INHIBITION; TOXICOLOGY C1 NIEHS,ENVIRONM IMMUN SECT,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. NR 42 TC 20 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1993 VL 21 IS 4 BP 535 EP 545 DI 10.1006/faat.1993.1130 PG 11 WC Toxicology SC Toxicology GA MG174 UT WOS:A1993MG17400016 PM 8253306 ER PT J AU DAWSEY, SM WANG, GQ WEINSTEIN, WM LEWIN, KJ LIU, FS WIGGETT, S NIEBERG, RK LI, JY TAYLOR, PR AF DAWSEY, SM WANG, GQ WEINSTEIN, WM LEWIN, KJ LIU, FS WIGGETT, S NIEBERG, RK LI, JY TAYLOR, PR TI SQUAMOUS DYSPLASIA AND EARLY ESOPHAGEAL CANCER IN THE LINXIAN REGION OF CHINA - DISTINCTIVE ENDOSCOPIC LESIONS SO GASTROENTEROLOGY LA English DT Article ID HIGH-RISK C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90024. NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. FU NCI NIH HHS [N01-CP-05634, N01-CP-95616] NR 17 TC 46 Z9 46 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 NOV PY 1993 VL 105 IS 5 BP 1333 EP 1340 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ME594 UT WOS:A1993ME59400010 PM 8224637 ER PT J AU EPSTEIN, SA GONZALES, JJ AF EPSTEIN, SA GONZALES, JJ TI OUTPATIENT CONSULTATION-LIAISON PSYCHIATRY - A VALUABLE ADDITION TO THE TRAINING OF ADVANCED PSYCHIATRY RESIDENTS SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID MODEL; CARE AB With current health care reimbursement conditions and recent research denoting the important relationship between mental health status and poor functioning, especially in medically ill patients, one would think that consultation-liaison (C-L) psychiatry would have an increasingly viable role in the outpatient health care sector. However, only a small number of outpatient C-L clinics are reported and recently several of these have folded. These outpatient C-L clinics can follow different clinical models and have the potential, especially at the residency and fellowship training levels, for interesting and useful educational opportunities. This paper describes a recently founded outpatient C-L clinic-the Medical Illness Clinic-in a university medical center's department of Psychiatry. We highlight the structure of the clinic, the kinds of patients seen, and focus on the unique educational residency training opportunities this setting presents. The results of clinic rotation evaluations by residents are also presented. We conclude with recommendations for more exploration of this clinical model and evaluation of its utility in psychiatric residency education. C1 NIMH,BETHESDA,MD 20892. RP EPSTEIN, SA (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,3750 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1993 VL 15 IS 6 BP 369 EP 374 DI 10.1016/0163-8343(93)90004-8 PG 6 WC Psychiatry SC Psychiatry GA MM995 UT WOS:A1993MM99500004 PM 8112559 ER PT J AU WILKIE, TM CHEN, Y GILBERT, DJ MOORE, KJ YU, L SIMON, MI COPELAND, NG JENKINS, NA AF WILKIE, TM CHEN, Y GILBERT, DJ MOORE, KJ YU, L SIMON, MI COPELAND, NG JENKINS, NA TI IDENTIFICATION, CHROMOSOMAL LOCATION, AND GENOME ORGANIZATION OF MAMMALIAN G-PROTEIN-COUPLED RECEPTORS SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; VISUAL PIGMENT GENES; COAT COLOR LOCUS; MOUSE CHROMOSOME-1; MOLECULAR-CLONING; MULTIGENE FAMILY; RESISTANCE LOCUS; MURINE; EXPRESSION; EVOLUTION C1 CALTECH,DIV BIOL 14775,PASADENA,CA 91125. INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 59 TC 68 Z9 79 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 NOV PY 1993 VL 18 IS 2 BP 175 EP 184 DI 10.1006/geno.1993.1452 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300001 PM 8288218 ER PT J AU REMMERS, EF GOLDMUNTZ, EA ZHA, HB MATHERN, P DU, Y CROFFORD, LJ WILDER, RL AF REMMERS, EF GOLDMUNTZ, EA ZHA, HB MATHERN, P DU, Y CROFFORD, LJ WILDER, RL TI LINKAGE MAP OF 9 LOCI DEFINED BY POLYMORPHIC DNA MARKERS ASSIGNED TO RAT CHROMOSOME-13 SO GENOMICS LA English DT Article ID BLOOD-PRESSURE; RENIN GENE; MOUSE; LOCALIZATION; NORVEGICUS; FRAGMENTS; PRIMERS; SINGLE; PCR RP REMMERS, EF (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 NR 22 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1993 VL 18 IS 2 BP 277 EP 282 DI 10.1006/geno.1993.1466 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300015 PM 8288230 ER PT J AU OKAZAKI, T YOSHIDA, BN AVRAHAM, KB WANG, HM WUENSCHELL, CW JENKINS, NA COPELAND, NG ANDERSON, DJ MORI, N AF OKAZAKI, T YOSHIDA, BN AVRAHAM, KB WANG, HM WUENSCHELL, CW JENKINS, NA COPELAND, NG ANDERSON, DJ MORI, N TI MOLECULAR DIVERSITY OF THE SCG10/STATHMIN GENE FAMILY IN THE MOUSE SO GENOMICS LA English DT Article ID NEURON-ENRICHED PHOSPHOPROTEIN; STAGE-SPECIFIC EXPRESSION; PROTEIN-KINASE SUBSTRATE; SPLICE JUNCTIONS; LINKAGE MAP; MAJOR PHOSPHOPROTEIN; CELL REGULATIONS; SILENCER ELEMENT; ACUTE-LEUKEMIA; TUMOR-CELLS C1 UNIV SO CALIF, ETHEL PERCY ANDRUS GERONTOL CTR, DIV NEUROGERONTOL, LOS ANGELES, CA 90089 USA. CALTECH, HOWARD HUGHES MED INST, DIV BIOL 21676, PASADENA, CA 91125 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. UNIV SO CALIF, SCH MED, LOS ANGELES, CA 90033 USA. FU NCI NIH HHS [N01-CO-74101]; NIA NIH HHS [AG07909] NR 53 TC 56 Z9 58 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV PY 1993 VL 18 IS 2 BP 360 EP 373 DI 10.1006/geno.1993.1477 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300026 PM 8288240 ER PT J AU SIMEK, SL KOZAK, CA WINTERSTEIN, D HEGAMYER, G COLBURN, NH AF SIMEK, SL KOZAK, CA WINTERSTEIN, D HEGAMYER, G COLBURN, NH TI SEQUENCE AND LOCALIZATION OF A NOVEL FK506-BINDING PROTEIN TO MOUSE CHROMOSOME-11 SO GENOMICS LA English DT Note ID RAPAMYCIN-BINDING-PROTEIN; ISOMERASE; CDNA; CLONING; FK-506 C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP SIMEK, SL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 12 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1993 VL 18 IS 2 BP 407 EP 409 DI 10.1006/geno.1993.1485 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300034 PM 7507077 ER PT J AU CERRETTI, DP NELSON, N KOZLOSKY, CJ MORRISSEY, PJ COPELAND, NG GILBERT, DJ JENKINS, NA DOSIK, JK MOCK, BA AF CERRETTI, DP NELSON, N KOZLOSKY, CJ MORRISSEY, PJ COPELAND, NG GILBERT, DJ JENKINS, NA DOSIK, JK MOCK, BA TI THE MURINE HOMOLOGUE OF THE HUMAN INTERLEUKIN-8 RECEPTOR-TYPE-B MAPS NEAR THE ITY-LSH-BCG DISEASE RESISTANCE LOCUS SO GENOMICS LA English DT Note ID MOUSE CHROMOSOME-1; GENE; HOST C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NCI,GENET LAB,BETHESDA,MD 20892. RP CERRETTI, DP (reprint author), IMMUNEX CORP,SEATTLE,WA 98101, USA. FU NCI NIH HHS [N01-CB-21075, N01-CO-74101] NR 21 TC 48 Z9 49 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 NOV PY 1993 VL 18 IS 2 BP 410 EP 413 DI 10.1006/geno.1993.1486 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300035 PM 8288247 ER PT J AU SPARKES, RS LEE, RH SHINOHARA, T CRAFT, CM KOJIS, T KLISAK, I HEINZMANN, C BATEMAN, JB AF SPARKES, RS LEE, RH SHINOHARA, T CRAFT, CM KOJIS, T KLISAK, I HEINZMANN, C BATEMAN, JB TI ASSIGNMENT OF THE PHOSDUCIN (PDC) GENE TO HUMAN-CHROMOSOME 1Q25-1Q32.1 BY SOMATIC-CELL HYBRIDIZATION AND IN-SITU HYBRIDIZATION SO GENOMICS LA English DT Note ID ROD OUTER SEGMENTS; INSITU HYBRIDIZATION; PHOTORECEPTOR CELLS; PROTEIN-KINASE; PINEAL-GLAND; BOVINE; PHOSPHOPROTEIN; RETINA; CDNA; TRANSDUCIN C1 UNIV CALIF LOS ANGELES, CTR HLTH SCI,JULES STEIN EYE INST, CTR VISION GENET,DEPT OPTHALMOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT ANAT & CELL BIOL, SEPULVEDA, CA 91343 USA. VET ADM MED CTR, DEV NEUROL LAB, SEPULVEDA, CA 91343 USA. NEI, RETINAL CELL & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV TEXAS, SW MED CTR, VET ADM MED CTR, DEPT PSYCHIAT, DALLAS, TX 75238 USA. RP SPARKES, RS (reprint author), UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, CTR VISION GENET, DEPT MED, LOS ANGELES, CA 90024 USA. OI Shinohara, Toshimichi/0000-0002-7197-9039 FU NEI NIH HHS [EY08282] NR 18 TC 15 Z9 15 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 NOV PY 1993 VL 18 IS 2 BP 426 EP 428 DI 10.1006/geno.1993.1490 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300039 PM 8288249 ER PT J AU DURKIN, AS MAGLOTT, DR VAMVAKOPOULOS, NC ZOGHBI, HY NIERMAN, WC AF DURKIN, AS MAGLOTT, DR VAMVAKOPOULOS, NC ZOGHBI, HY NIERMAN, WC TI ASSIGNMENT OF AN INTRON-CONTAINING HUMAN HEAT-SHOCK PROTEIN GENE (HSP90-BETA, HSPCB) TO CHROMOSOME-6 NEAR TCTE1 (6P21) AND 2 INTRONLESS PSEUDOGENES TO CHROMOSOME-4 AND CHROMOSOME-15 BY POLYMERASE CHAIN-REACTION AMPLIFICATION FROM A PANEL OF HYBRID CELL-LINES SO GENOMICS LA English DT Note ID SEQUENCE; FAMILY; PCR C1 AMER TYPE CULTURE COLLECT,DEPT MOLEC BIOL,ROCKVILLE,MD 20852. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. AMER TYPE CULTURE COLLECT,DEPT BIOINFORMAT,ROCKVILLE,MD 20852. NR 14 TC 10 Z9 10 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 NOV PY 1993 VL 18 IS 2 BP 452 EP 454 DI 10.1006/geno.1993.1498 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300047 PM 8288256 ER PT J AU VAMVAKOPOULOS, NC ROJAS, K OVERHAUSER, J DURKIN, AS NIERMAN, WC CHROUSOS, GP AF VAMVAKOPOULOS, NC ROJAS, K OVERHAUSER, J DURKIN, AS NIERMAN, WC CHROUSOS, GP TI MAPPING THE HUMAN MELANOCORTIN-2 RECEPTOR (ADRENOCORTICOTROPIC HORMONE-RECEPTOR ACTHR) GENE (MC2R) TO THE SMALL ARM OF CHROMOSOME-18 (18P11.21-PTER) SO GENOMICS LA English DT Note ID DELETION; MAP C1 THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. AMER TYPE CULTURE COLLECT,DEPT MOLEC BIOL,ROCKVILLE,MD 20852. RP VAMVAKOPOULOS, NC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N-240,BETHESDA,MD 20892, USA. NR 11 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1993 VL 18 IS 2 BP 454 EP 455 DI 10.1006/geno.1993.1499 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300048 PM 8288257 ER PT J AU TSUDA, T CUTLER, ML AF TSUDA, T CUTLER, ML TI HUMAN RSU1 IS HIGHLY HOMOLOGOUS TO MOUSE RSU-1 AND LOCALIZES TO HUMAN-CHROMOSOME-10 SO GENOMICS LA English DT Note ID SACCHAROMYCES-CEREVISIAE; ADENYLYL CYCLASE; RAS C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 4 TC 11 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1993 VL 18 IS 2 BP 461 EP 462 DI 10.1006/geno.1993.1503 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MG993 UT WOS:A1993MG99300052 PM 8288261 ER PT J AU BUTLER, RN AHRONHEIM, J FILLIT, H RAPOPORT, SI TATEMICHI, TK AF BUTLER, RN AHRONHEIM, J FILLIT, H RAPOPORT, SI TATEMICHI, TK TI VASCULAR DEMENTIA - STROKE PREVENTION TAKES ON NEW URGENCY - A ROUND-TABLE DISCUSSION .1. SO GERIATRICS LA English DT Discussion ID CEREBRAL BLOOD-FLOW AB Vascular dementia is a clinical syndrome of acquired intellectual impairment resulting from brain injury due to a cerebrovascular disorder. It is a complex diagnosis, and diagnostic criteria vary. In community practice, the physician can probably make the diagnosis based on the history and medical examination. CT demonstration of one or more infarcts increases the likelihood of this diagnosis. Hypertension is a major risk factor for vascular dementia. Others include smoking, hyperlipidemia, atrial fibrillation, diabetes, and a sedentary lifestyle. Cerebrovascular disease is an important cause of cognitive decline in older patients. Therefore, it is important to recognize risk factors for stroke and institute measures for prevention. C1 MT SINAI MED CTR,DEPT GERIATR & ADULT DEV & MED,NEW YORK,NY 10029. NIA,NEUROSCI LAB,NEW YORK,NY. COLUMBIA UNIV COLL PHYS & SURG,INST NEUROSURG,STROKE & AGING RES PROJECT,NEW YORK,NY 10032. MT SINAI MED CTR,GERIATR CONSULTAT & LIAISON SERV,NEW YORK,NY 10029. RP BUTLER, RN (reprint author), MT SINAI MED CTR,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 13 TC 9 Z9 9 U1 0 U2 2 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD NOV PY 1993 VL 48 IS 11 BP 32 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MG826 UT WOS:A1993MG82600012 PM 8224925 ER PT J AU FREO, U LARSON, DM SONCRANT, TT AF FREO, U LARSON, DM SONCRANT, TT TI CEREBRAL METABOLIC RESPONSES TO META-CHLOROPHENYLPIPERAZINE ARE REDUCED DURING ITS CHRONIC ADMINISTRATION TO YOUNG AND AGED RATS SO GERONTOLOGY LA English DT Article DE [C-14] 2-DEOXYGLUCOSE; SEROTONIN; META-CHLOROPHENYLPIPERAZINE; AGING; PLASTICITY ID AWAKE RATS; SEROTONIN RECEPTORS; GLUCOSE-UTILIZATION; FOOD-INTAKE; AGONIST; BRAIN; TRIFLUOROMETHYLPHENYLPIPERAZINE; FOREBRAIN; LOCOMOTOR; SYSTEMS AB The effects of the 5-HT agonist meta-chlorophenylpiperazine (MCPP) on regional cerebral metabolic rates for glucose (rCMRglc) were measured in 3- and 24-month-old rats that were not pretreated or were pretreated for 2 weeks with continuous infusion of saline or MCPP. rCMRglc were measured using the quantitative autoradiographic [C-14]2-deoxy-D-glucose technique in 71 brain regions at 15 min after acute administration of MCPP 2.5 mg/kg. In the absence of chronic pretreatment, intraperitoneal MCPP 2.5mg/kg produced widespread rCMRglc reductions (41 brain areas) in 3-month-old rats and more limited rCMRglc decreases (8 brain areas) in 24-month-old rats. After chronic treatment, MCPP failed to reduce rCMRglc in any region of either group of rats. These findings indicate that mechanisms of downregulation of response to MCPP are functional in young and aged rats and suggest that the age-related reduction in rCMRglc responses to acute MCPP in non-pretreated animals may be due to compensation for age-related losses of 5-HT terminals. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 33 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD NOV-DEC PY 1993 VL 39 IS 6 BP 305 EP 313 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MT341 UT WOS:A1993MT34100001 PM 8144044 ER PT J AU MANSOUR, AM ANSARI, NH EGWUAGU, CE KASPAR, HG HARMON, MK AF MANSOUR, AM ANSARI, NH EGWUAGU, CE KASPAR, HG HARMON, MK TI BACTERIAL OPTIC DISK MASS AND TOXOPLASMIC-LIKE ENCEPHALITIS IN AN HIV-SEROPOSITIVE SUBJECT SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; GONDII C1 UNIV TEXAS,MED BRANCH,DEPT OPHTHALMOL,GALVESTON,TX 77555. NEI,IMMUNOL LAB,BETHESDA,MD 20892. ST JOHNS MERCY MED CTR,DEPT PATHOL,ST LOUIS,MO 63141. FU NEI NIH HHS [EY 08547-02] NR 12 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD NOV PY 1993 VL 231 IS 11 BP 668 EP 671 DI 10.1007/BF00921964 PG 4 WC Ophthalmology SC Ophthalmology GA MC885 UT WOS:A1993MC88500011 PM 8258404 ER PT J AU JERIAN, SM SAROSY, GA LINK, CJ FINGERT, HJ REED, E KOHN, EC AF JERIAN, SM SAROSY, GA LINK, CJ FINGERT, HJ REED, E KOHN, EC TI INCAPACITATING AUTONOMIC NEUROPATHY PRECIPITATED BY TAXOL SO GYNECOLOGIC ONCOLOGY LA English DT Note ID PHASE-I; CANCER; AGENT; TRIAL C1 NCI,MED BRANCH,BETHESDA,MD 20892. ST ELIZABETHS HOSP BOSTON,BOSTON,MA 02135. NR 10 TC 34 Z9 34 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 1993 VL 51 IS 2 BP 277 EP 280 DI 10.1006/gyno.1993.1287 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA MQ993 UT WOS:A1993MQ99300027 PM 7903950 ER PT J AU HAMRICK, PE DAVIDSON, WE VELAZQUEZ, KW WATSON, JE AF HAMRICK, PE DAVIDSON, WE VELAZQUEZ, KW WATSON, JE TI MONITORING OF S-35 IN ASH OF INCINERATED WASTE SO HEALTH PHYSICS LA English DT Article DE RADIOACTIVITY; INCINERATION; S-35; WASTE DISPOSAL AB The National Institute of Environmental Health Sciences incinerates low-level radioactive waste containing H-3, C-14, and S-35 as a means of volume reduction. The primary isotope remaining in the ash is S-35. Some effects of the chemical and physical form of the waste on sulfur retention in ash and several methods for determining the activity remaining in the ash have been explored. It was found that the sulfur in sodium sulfate has a higher retention in ash than the sulfur in methionine and that the presence of glass appears to enhance the retention. Liquid scintillation and proportional counting methods were compared. A sulfur extraction procedure using liquid scintillation counting was found to give the lowest minimum detectable activity. However, it was determined that a more practical method for routine monitoring is to suspend a small quantity of ash in a liquid scintillation gel. C1 US NUCL REGULATORY COMMISS, KING OF PRUSSIA, PA 19406 USA. N CAROLINA DIV RADIAT PROTECT, RALEIGH, NC 27611 USA. UNIV N CAROLINA, DEPT ENVIRONM SCI & ENGN, CHAPEL HILL, NC 27599 USA. RP HAMRICK, PE (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 1993 VL 65 IS 5 BP 556 EP 559 DI 10.1097/00004032-199311000-00016 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA ME861 UT WOS:A1993ME86100021 PM 8225997 ER PT J AU NAKATSUKASA, H SILVERMAN, JA GANT, TW EVARTS, RP THORGEIRSSON, SS AF NAKATSUKASA, H SILVERMAN, JA GANT, TW EVARTS, RP THORGEIRSSON, SS TI EXPRESSION OF MULTIDRUG-RESISTANCE GENES IN RAT-LIVER DURING REGENERATION AND AFTER CARBON-TETRACHLORIDE INTOXICATION SO HEPATOLOGY LA English DT Article ID P-GLYCOPROTEIN; MESSENGER-RNA; FAMILY; HEPATOCARCINOGENESIS; CARCINOGENS; FIBROSIS; TISSUES; GROWTH; CELLS; ACID AB We analyzed expression of multidrug resistance (mdr) genes in rat liver during regeneration after partial hepatectomy or carbon tetrachloride-induced necrosis. In situ hybridization revealed that in the normal liver the cellular distribution of mdr transcripts and protein is restricted to hepatocytes and that a gradient, highest in zone 1 and lowest in zone 3, exists in the level of the mdr transcripts in the liver acinus. Increased levels of mdr1a and mdr1b transcripts were observed 3 hr after administration of carbon tetrachloride and remained increased for the next 5 days. In contrast, increased expression of mdr1a and mdr1b was first observed 24 hr after partial hepatectomy. Use of gene-specific probes to compare the time courses of mdr1b and mdr2 expression after carbon tetrachloride administration showed distinctly different patterns of expression; mdr1b reached a maximum level of expression at 12 hr, whereas increased mdr2 expression was first observed 48 hr after administration. Nuclear run-on analysis at 12 and 24 hr after carbon tetrachloride administration demonstrated 10-fold and eightfold increases in mdr transcription, respectively. However, 72 hr after carbon tetrachloride treatment the rate of mdr transcription was back to the control level. The cellular patterns of mdr expression after partial hepatectomy and carbon tetrachloride administration were similar; the increase was first observed in zone 1 and gradually extended into zone 3. These data strongly suggest that the physiological roles of mdr1b and mdr2 are different and that liver regeneration is an appropriate model for elucidating these differences. C1 NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 27 TC 67 Z9 68 U1 0 U2 1 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 NOV PY 1993 VL 18 IS 5 BP 1202 EP 1207 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ME769 UT WOS:A1993ME76900027 PM 7693574 ER PT J AU ANAGNOU, NP SEUANEZ, H MODI, W OBRIEN, SJ PAPAMATHEAKIS, J MOSCHONAS, NK AF ANAGNOU, NP SEUANEZ, H MODI, W OBRIEN, SJ PAPAMATHEAKIS, J MOSCHONAS, NK TI CHROMOSOMAL MAPPING OF 2 MEMBERS OF THE HUMAN GLUTAMATE-DEHYDROGENASE (GLUD) GENE FAMILY TO CHROMOSOMES 10Q22.3-Q23 AND XQ22-Q23 SO HUMAN HEREDITY LA English DT Article DE GLUTAMATE DEHYDROGENASE GENE FAMILY; HUMAN GENE MAPPING; CHROMOSOMES 10 AND X ID POLYMORPHISM; DEFICIENCY AB Glutamate dehydrogenase (GLUD) is an important mitochondrial enzyme that participates in neuronal transmission by catalyzing the deamination of L-glutamate, which serves as a potent excitatory neurotransmitter. The direct involvement of GLUD in the pathogenesis of certain human neurodegenerative disorders has been suggested recently. To investigate its possible role in the induction and progression of these disorders, we have initiated studies focusing on the chromosomal organization of the several members of the GLUD family and their functional status. In the present study using a panel of human x rodent somatic cell hybrids and in situ hybridization to metaphase chromosomes, we documented that the members of the GLUD gene family are dispersed in the human genome. The functional GLUD1 gene was mapped to chromosome 10q22.3-q23, and an intronless processed gene (GLUDP1) to chromosome Xq22-q23, while the truncated intron-containing GLUD pseudogene GLUDP2 was also assigned on chromosome 10, but not closely linked to the GLUD1 gene. These results provide novel information concerning the chromosomal organization of the human GLUD gene family. C1 UNIV CRETE,DEPT BIOL,IRAKLION,GREECE. UNIV CRETE,SCH MED,IRAKLION,GREECE. DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS PROGRAM,FREDERICK,MD. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP ANAGNOU, NP (reprint author), FDN RES & TECHNOL,INST MOLEC BIOL & BIOTECHNOL,POB 1527,GR-71110 IRAKLION,GREECE. FU NINDS NIH HHS [NS-16871] NR 17 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD NOV-DEC PY 1993 VL 43 IS 6 BP 351 EP 356 DI 10.1159/000154158 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MM858 UT WOS:A1993MM85800004 PM 8288265 ER PT J AU VELDHUIS, JD DUFAU, ML AF VELDHUIS, JD DUFAU, ML TI STEROIDAL REGULATION OF BIOLOGICALLY-ACTIVE LUTEINIZING-HORMONE SECRETION IN MEN AND WOMEN SO HUMAN REPRODUCTION LA English DT Article; Proceedings Paper CT INTERNATIONAL FERRING SYMPOSIUM ON CENTRAL CONTROL OF GONADAL FUNCTION CY SEP 07-08, 1992 CL SCHLOSS REINHGARTSHAUSEN, ELTVILLE, GERMANY SP FERRING GMBH HO SCHLOSS REINHGARTSHAUSEN DE BIOACTIVE; GONADOTROPIN; HUMAN; PITUITARY; PULSATILE ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; INDUCED LH SURGE; POSTMENOPAUSAL WOMEN; PITUITARY RESPONSIVENESS; PULSATILE SECRETION; INVITRO BIOASSAY; MENSTRUAL-CYCLE; PURE ESTRADIOL; ESTROUS-CYCLE AB The biological activity of circulating luteinizing hormone (LH) molecules can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to immunoreactive estimates of the LH content of plasma, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflecting the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiological regulation by steroid hormones of bioactive LH secretion and clearance in men and women. Our investigations and those in the available literature indicate that: (i) exogenous (non-aromatizable) 5-alpha-dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion of biopotent LH in men; (ii) endogenous androgen excess due to a masculinizing testosterone-secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas the antioestrogen, tamoxifen-HCI, can increase bioactive LH secretion in young men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v) endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration, whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal (oestradiol-impregnated silastic ring), exerts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5 - 10 days), and longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency, and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin releasing hormone (GnRH)'s stimulatory action on biologically active LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oestrogen augments LH secretory burst mass and duration. Moreover, GnRH dose-LH secretory response studies show that oestrogen promotes an increase in GnRH efficacy (maximal effects) but not GnRH sensitivity (potency or half-maximally effective doses of GnRH). We conclude that steroid hormones are primary regulators of physiologically pulsatile bioactive LH secretion in healthy men and women. Moreover, steroids exert potent pathological effects on biologically active LH release in conditions of selective hyperandrogenism or hyperoestrogenism due to steroid-secreting adrenal or gonadal tumours. C1 NICHHD,ENDOCRINE REPROD RES BRANCH,BETHESDA,MD 20205. RP VELDHUIS, JD (reprint author), UNIV VIRGINIA,HLTH SCI CTR,NATL SCI FDN CTR BIOL TIMING,DEPT INTERNAL MED,DIV ENDOCRINOL,CHARLOTTESVILLE,VA 22908, USA. FU NCRR NIH HHS [RR-00847]; NICHD NIH HHS [1-KO4-HD00634]; NIDDK NIH HHS [DK-38942] NR 71 TC 13 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1993 VL 8 SU 2 BP 84 EP 96 PG 13 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA MJ684 UT WOS:A1993MJ68400017 PM 8276976 ER PT J AU SCHAUER, DB FALKOW, S AF SCHAUER, DB FALKOW, S TI THE EAE GENE OF CITROBACTER-FREUNDII BIOTYPE 4280 IS NECESSARY FOR COLONIZATION IN TRANSMISSIBLE MURINE COLONIC HYPERPLASIA SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; EPITHELIAL-CELLS; ADHERENCE FACTOR; VIBRIO-CHOLERAE; DNA PROBE; PLASMID; DIARRHEA; RABBIT; CONSTRUCTION; DETERMINANT AB Transmissible murine colonic hyperplasia is characterized by proliferation of anchored stem cells in the mucosa of the descending colon of laboratory mice and is caused by Citrobacter freundii biotype 4280. This bacterium produces attaching and effacing lesions in the descending colon prior to the onset of gross hyperplasia. By mutational analysis, the chromosomal eae gene of C freundii biotype 4280 was shown to be necessary for colonic colonization. Conversely, bacteria cured of a 65-kb plasmid, which was identified in C. freundii biotype 4280, were not attenuated for colonic colonization or for the induction of colonic hyperplasia. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. FU NIAID NIH HHS [AI26195] NR 42 TC 120 Z9 120 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 NOV PY 1993 VL 61 IS 11 BP 4654 EP 4661 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ME617 UT WOS:A1993ME61700017 PM 8406863 ER PT J AU ROILIDES, E UHLIG, K VENZON, D PIZZO, PA WALSH, TJ AF ROILIDES, E UHLIG, K VENZON, D PIZZO, PA WALSH, TJ TI PREVENTION OF CORTICOSTEROID-INDUCED SUPPRESSION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE-INDUCED DAMAGE OF ASPERGILLUS-FUMIGATUS HYPHAE BY GRANULOCYTE-COLONY-STIMULATING FACTOR AND GAMMA-INTERFERON SO INFECTION AND IMMUNITY LA English DT Article ID CANDIDA-ALBICANS HYPHAE; TUMOR-NECROSIS-FACTOR; NEUTROPHIL RESPIRATORY BURST; RAPID COLORIMETRIC ASSAY; SIGNAL TRANSDUCTION; SUPEROXIDE RELEASE; HUMAN MACROPHAGES; CUSHINGS-SYNDROME; BINDING-PROTEIN; HOST DEFENSE AB Neutrophils (PMNs) are a critical line of defense against Aspergillus fumigatus infection. Increased frequency of invasive aspergillosis has been observed in patients receiving corticosteroids, suggesting a deleterious effect of these compounds on PMN antifungal function. To investigate this hypothesis and to determine the potential preventive utility of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma), the effects of hydrocortisone (HCS) and dexamethasone (DXS) on PMN-induced damage of Aspergillus fumigatus hyphae were studied with or without pretreatment of PMNs with G-CSF and IFN-gamma. PMNs treated with HCS (greater-than-or-equal-to 3,000 muM) or DXS (greater-than-or-equal-to 10 muM) during a 2-h colorimetric tetrazolium metabolic assay (using methylthiotetrazolium) showed suppressed percentage of hyphal damage (P < 0.02). In addition, both HCS (greater-than-or-equal-to 30 muM) and DXS (greater-than-or-equal-to 1 muM) significantly suppressed oxidative burst measured as superoxide anion release by PMNs in response to opsonized and nonopsonized hyphae as well as to N-formylmethionyl leucyl phenylalanine. Pretreatment of PMNs with G-CSF (4,000 U/ml) and/or IFN-gamma (100 and 1,000 U/ml) for 90 min prevented the suppression of hyphal damage that occurred in the presence of HCS (3,000 muM; P < 0.01) or DXS (10 muM; P less-than-or-equal-to 0.001). G-CSF (4,000 U/ml) and IFN-gamma (100 U/ml) combined had an additive effect on increasing the antifungal activity of HCS-treated but not of DXS-treated PMNs compared with IFN-gamma alone (P = 0.015). Thus, these findings reveal that corticosteroids impair PMN function in response to A. fumigatus and that G-CSF and IFN-gamma prevent this impairment. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 59 TC 141 Z9 145 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 NOV PY 1993 VL 61 IS 11 BP 4870 EP 4877 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ME617 UT WOS:A1993ME61700046 PM 7691757 ER PT J AU FULTZ, MJ BARBER, SA DIEFFENBACH, CW VOGEL, SN AF FULTZ, MJ BARBER, SA DIEFFENBACH, CW VOGEL, SN TI INDUCTION OF IFN-GAMMA IN MACROPHAGES BY LIPOPOLYSACCHARIDE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE C3H/HEJ; ENDOTOXIN; POLYINOSINIC POLYCYTIDYLIC ACID ID TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; ENDOGENOUS INTERFERON; MURINE MACROPHAGES; C3H-HEJ MICE; MESSENGER-RNA; ACTIVATION; ENDOTOXIN; RECEPTOR AB In this paper we report that macrophages can be stimulated to express detectable levels of IFN-gamma-specific mRNA. Macrophages from lipopolysaccharide (LPS)-responsive, C3H/OuJ mice are induced by LPS to increase steady-state levels of IFN-gamma-specific mRNA, while those from LPS-hyporesponsive C3H/HeJ mice are not. This interstrain variation is apparently the result of LPS-specific signal differences since macrophages derived from both Lps(n) and Lps(d) mouse strains are able to produce comparable levels of IFN-gamma-specific mRNA following stimulation with polyinosinic - polycytidylic acid. The identity of the cell type responsible f or this IFN-gamma message appears to be the macrophage as IFN-gamma-specific mRNA was also detectable following T and natural killer cell depletion, in the LPS-stimulated RAW 264.7 cell line, and in a homogeneous population of mature macrophages propagated in vitro by stimulation of bone marrow progenitors with recombinant colony stimulating factor-1. Immunofluorescent staining of fixed and permeabilized LPS-stimulated macrophages confirmed the presence of immunoreactive IFN-gamma protein. The possible significance of IFN-gamma production by macrophages is discussed in the context of normal macrophage differentiation as well as the inflammatory immune response. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. NIAID,DIV AIDS,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-18797] NR 51 TC 136 Z9 136 U1 0 U2 4 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 NOV PY 1993 VL 5 IS 11 BP 1383 EP 1392 DI 10.1093/intimm/5.11.1383 PG 10 WC Immunology SC Immunology GA MH094 UT WOS:A1993MH09400004 PM 8260452 ER PT J AU DAERON, M MALBEC, O LATOUR, S BONNEROT, C SEGAL, DM FRIDMAN, WH AF DAERON, M MALBEC, O LATOUR, S BONNEROT, C SEGAL, DM FRIDMAN, WH TI DISTINCT INTRACYTOPLASMIC SEQUENCES ARE REQUIRED FOR ENDOCYTOSIS AND PHAGOCYTOSIS VIA MURINE FC-GAMMA-RII IN MAST-CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE IMMUNE COMPLEXES; MURINE LOW-AFFINITY RECEPTORS FOR IGG; RAT BASOPHILIC LEUKEMIA CELLS; RECEPTOR-MEDIATED INTERNALIZATION; SITE-DIRECTED MUTAGENESIS ID BASOPHILIC LEUKEMIA-CELLS; COATED PIT LOCALIZATION; IMMUNOGLOBULIN-E; BOUND LIGANDS; IGE RECEPTORS; MACROPHAGE; INTERNALIZATION; ANTIBODY; SUBUNIT; DOMAINS AB In the present work, we studied the phagocytic and endocytic properties of murine FcgammaRII in mast cells. Mouse mast cells express high-affinity receptors for monomeric IgE and three low-affinity receptors for complexed IgG: FcgammaRIIb1, FcgammaRIIb2, and FcgammaRIII. In previous studies we showed that, when aggregated by multivalent ligands, murine FcgammaRIIl, but not FcgammaRII, triggers the release of inflammatory mediators and cytokines by mast cells. Upon FcgammaR aggregation, mast cells not only release intracellular materials, they also internalize particulate and soluble immune complexes. We compared the ability of the two FcgammaRII isoforms to trigger phagocytosis and endocytosis in RBL-2H3 cells stably transfected with cDNAs encoding wild-type, deleted, and tyrosine mutant FcgammaRIIb1 or FcgammaRIIb2. We found that FcgammaRIIb2, but not FcgamaRIIb1, triggered both phagocytosis and endocytosis. We identified distinct intracytoplasmic sequences necessary for FcgammaRIIb2-mediated endocytosis and phagocytosis respectively, and we observed that two tyrosine residues, located in each of these sequences, are critical for endocytosis and/or phagocytosis. Our data indicate that the two internalization pathways diverge as early as signal transduction. C1 NCI,EXPTL IMMUNOL BRANCH,IMMUNE TARGETING SECT,BETHESDA,MD 20892. RP DAERON, M (reprint author), INST CURIE,INSERM,U255,IMMUNOL CELLULAIRE & CLIN LAB,26 RUE ULM,F-75005 PARIS,FRANCE. NR 39 TC 41 Z9 41 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 NOV PY 1993 VL 5 IS 11 BP 1393 EP 1401 DI 10.1093/intimm/5.11.1393 PG 9 WC Immunology SC Immunology GA MH094 UT WOS:A1993MH09400005 PM 8260453 ER PT J AU JARVIK, GP WIJSMAN, E LITTLE, RE ALBERS, JJ MOTULSKY, AG BRUNZELL, JD AF JARVIK, GP WIJSMAN, E LITTLE, RE ALBERS, JJ MOTULSKY, AG BRUNZELL, JD TI HOST AND ENVIRONMENTAL-EFFECTS ON PLASMA APOLIPOPROTEIN-B SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Article DE APOLIPOPROTEIN-B; CHOLESTEROL; LOW-DENSITY LIPOPROTEIN ID CORONARY HEART-DISEASE; DENSITY LIPOPROTEIN CHOLESTEROL; A-I; SERUM-LIPIDS; MYOCARDIAL-INFARCTION; ALCOHOL-CONSUMPTION; ANTIHYPERTENSIVE DRUGS; PARENTAL HISTORY; ARTERY DISEASE; RISK-FACTORS AB In this study, levels of apo B in an unselected sample of 487 middle-aged Caucasian spouses of patients and spouses of the patients' relatives are described. In males, apo B levels increased with age until the 7th decade, then declined; apo B levels in females, which were lower than in males, increased linearly with age across the entire life-span. Height and weight, smoking, and presence of noninsulin-dependent diabetes mellitus significantly influenced age- and gender-adjusted apo B levels in this sample, whereas use of alcohol, diuretics, beta-blockers, or insulin did not. Age, gender, height, weight, smoking, and noninsulin-dependent diabetes mellitus account for 21% of the total variation in apo B levels in this sample. C1 UNIV WASHINGTON,DEPT MED,DIV METAB ENDOCRINOL & NUTR RG26,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,DIV MED GENET RG25,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU NHLBI NIH HHS [HL 30086] NR 40 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD NOV PY 1993 VL 23 IS 4 BP 215 EP 220 DI 10.1007/BF02592312 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MH400 UT WOS:A1993MH40000008 PM 8123878 ER PT J AU MILLER, AC GAFNER, J CLARK, EP SAMID, D AF MILLER, AC GAFNER, J CLARK, EP SAMID, D TI DIFFERENCES IN RADIATION-INDUCED MICRONUCLEI YIELDS OF HUMAN-CELLS - INFLUENCE OF RAS GENE-EXPRESSION AND PROTEIN LOCALIZATION SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; FIELD GEL-ELECTROPHORESIS; H-RAS; TRANSFORMED-CELLS; HUMAN-FIBROBLASTS; V-MYC; DNA; RADIOSENSITIVITY; ONCOGENE; ASSAY AB Expression of ras has been correlated with increased intrinsic resistance to ionizing radiation. In this study we show that increased EJras expression in human cells is associated with a decrease in the frequency of radiation-induced micronuclei. The experimental system consisted of human osteosarcoma-derived cell lines which quantitatively vary in their EJras expression. There was a dose-dependent relationship between radiation dose and micronuclei formation in all cell lines tested. Human osteosarcoma cells, in which the ras level was undetectable, had the highest frequency of micro-nuclei production at all radiation doses tested. At 4 Gy the most radioresistant cells exhibited a 41.5 +/- 5% decrease in the production of micronuclei concomitant with high ras expression in comparison with the relatively radiosensitive parental cell line. Cells expressing a low amount of EJras demonstrated a 23 +/- 3% decrease in micronuclei induction compared with parental cells. Treatment of cells with lovastatin, an inhibitor of ras-encoded p21ras post-translational processing via the mevalonate pathway, markedly decreased the yield of micronuclei formation in cells transfected with ras; the drug had no effect on radiation-induced micronuclei formation in parental cells. The use of the in vitro micronuclei assay has provided a convenient way to visualize differences in the genotoxic damage induced by ionizing radiation in cells which express different amount of Ejras. The results indicate that elevation of ras expression in human cells can lead to a decrease in the number of radiation-induced micronuclei formed and that this relationship is dependent on membrane association of ras-encoded p21. C1 NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20814. RP MILLER, AC (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT RADIAT BIOCHEM,BETHESDA,MD 20889, USA. FU NEI NIH HHS [R03 EY08220-01] NR 32 TC 15 Z9 16 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV PY 1993 VL 64 IS 5 BP 547 EP 554 DI 10.1080/09553009314551761 PG 8 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA MK204 UT WOS:A1993MK20400008 PM 7902394 ER PT J AU KRAUSE, RM AF KRAUSE, RM TI EMERGING PATTERNS OF HETEROSEXUAL HIV-INFECTION AND TRANSMISSION - CLOSING STATEMENT SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Editorial Material RP KRAUSE, RM (reprint author), NIH,FOGARTY INT CTR ADV STUDY HLTH SCI,BLDG 31,ROOM B2CO2,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD NOV-DEC PY 1993 VL 4 IS 6 BP 357 EP 362 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MM376 UT WOS:A1993MM37600012 PM 8305579 ER PT J AU KATZ, ML WHITE, HA GAO, CL ROTH, GS KNAPKA, JJ INGRAM, DK AF KATZ, ML WHITE, HA GAO, CL ROTH, GS KNAPKA, JJ INGRAM, DK TI DIETARY RESTRICTION SLOWS AGE PIGMENT ACCUMULATION IN THE RETINAL-PIGMENT EPITHELIUM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE AGING; LIPOFUSCIN; RETINA; CALORIC RESTRICTION; DIETARY FIBER ID LIFELONG HYPOCALORIC DIET; MACULAR DEGENERATION; LIPOFUSCIN-LIKE; CELL LOSS; RATS; LIGHT AB Purpose. The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restriction has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to determine if dietary restriction alters the rate of age pigment accumulation in the RPE. Methods. Male Wistar rats were placed on one of three dietary regimens starting at weaning. One group was fed a nutritionally complete diet ad libitum. Another group was fed the same diet but was only allowed to consume 60% as much food daily as the ad libitum group ate. The final group was fed ad libitum a nutritionally complete diet that had a lower caloric density per gram than the diets fed to the other animals primarily because of the replacement of carbohydrate with oat fiber. Ultrastructural morphometric analysis was used to determine the RPE age pigment content in the first group at 6 months of age, and in all of the groups at 18 months of age. Results. Dietary restriction, achieved either by reducing total food intake or by reducing the caloric content of the diet, resulted in significant decreases in RPE lipofuscin accumulation. Conclusions. Dietary restriction provides a relatively simple means by which RPE age pigment content can be modulated. This should prove useful in assessing the role of RPE lipofuscin accumulation in age-related retinal disorders. That the oat fiber diet fed ad libitum was almost as effective as restriction of total food intake in slowing RPE age pigment accumulation indicates that the effect of restricted caloric intake is not mediated by almost constant hunger. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. RP KATZ, ML (reprint author), UNIV MISSOURI,SCH MED,MASON INST OPHTHALMOL,COLUMBIA,MO 65212, USA. FU NEI NIH HHS [EY08813, EY06458] NR 36 TC 12 Z9 12 U1 0 U2 3 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 NOV PY 1993 VL 34 IS 12 BP 3297 EP 3302 PG 6 WC Ophthalmology SC Ophthalmology GA MF621 UT WOS:A1993MF62100009 PM 8225864 ER PT J AU DELCERRO, M SEIGEL, GM LAZAR, E GROVER, D DELCERRO, C BROOKS, DH DILORETO, D CHADER, G AF DELCERRO, M SEIGEL, GM LAZAR, E GROVER, D DELCERRO, C BROOKS, DH DILORETO, D CHADER, G TI TRANSPLANTATION OF Y79 CELLS INTO RAT EYES - AN IN-VIVO MODEL OF HUMAN RETINOBLASTOMAS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Y79 CELLS; RETINOBLASTOMA; RETINAL TRANSPLANTATION; RETINA; TUMOR ID RETINAL S-ANTIGEN; INTRARETINAL TRANSPLANTATION; TRILATERAL RETINOBLASTOMA; MONOCLONAL-ANTIBODY; GLIAL MARKERS; MOUSE; Y-79; DIFFERENTIATION; MIGRATION; PROTEIN AB Purpose. To develop an in vivo model of human retinoblastoma by returning cultured Y79 retinoblastoma cells to the retinal environment of a widely available laboratory animal. In so doing, to study the survival, integration, and invasive characteristics expressed by tumoral cells grafted into an intraocular milieu from which these progenitor cells originated more than 20 years ago. Methods. Using the retinal grafting method of Lazar and del Cerro, Y79 cells were injected under direct visualization into the subretinal space of Fischer 344 rats. The host rats included 36 animals that received daily injections of cyclosporin A and 4 that did not. All hosts were sacrificed 30 to 60 days after transplantation. Results. Clinical examination showed vitreal invasion by masses of flocculent white material or the intravitreal formation of solid tumors. Histologic examination showed these formations to be outgrowths of grafted tumoral cells into the host retina and vitreal cavity. Highly anaplastic tumoral cells were also found lodged in subretinal and intraretinal locations. There were signs of continued and intense cell division within the grafts, with no indication of cell-mediated host reaction against the grafted cells. Conclusions. After intraretinal xenografting, human Y79 retinoblastoma cells retain a highly tumoral nature despite many years of in vitro propagation. When xenografted, these cells survive, grow, and express their malignancy within the retina of the common laboratory rat protected by a moderate immunosuppressive regimen. This partial immunosuppression is a requirement for the xenografts to prosper. This model offers a valuable opportunity to study in vivo the cellular and molecular biology of this and other human retinoblastomas, and it may facilitate the evaluation of antitumoral treatments. C1 UNIV ROCHESTER,SCH MED,CTR VISUAL SCI,ROCHESTER,NY 14627. UNIV ROCHESTER,SCH MED,DEPT OPHTHALMOL,ROCHESTER,NY 14627. NIH,BETHESDA,MD 20892. RP DELCERRO, M (reprint author), UNIV ROCHESTER,SCH MED,DEPT NEUROBIOL & ANAT,POB 603,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NIA NIH HHS [T32AG00107]; PHS HHS [NEI 05262] NR 40 TC 19 Z9 19 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 NOV PY 1993 VL 34 IS 12 BP 3336 EP 3346 PG 11 WC Ophthalmology SC Ophthalmology GA MF621 UT WOS:A1993MF62100014 PM 8225869 ER PT J AU KAHN, CR YOUNG, E LEE, IH RHIM, JS AF KAHN, CR YOUNG, E LEE, IH RHIM, JS TI HUMAN CORNEAL EPITHELIAL PRIMARY CULTURES AND CELL-LINES WITH EXTENDED LIFE-SPAN - IN-VITRO MODEL FOR OCULAR STUDIES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE HUMAN CORNEAL EPITHELIUM; IMMORTALIZED EPITHELIAL CELL LINES; IN-VITRO MODEL; SERUM-FREE MEDIUM; TRANSEPITHELIAL PERMEABILITY ID SV40 T-ANTIGEN; NEOPLASTIC TRANSFORMATION; HYBRID VIRUS; EXPRESSION; KERATINOCYTES AB Purpose. To develop an in vitro model of human corneal epithelium that can be propagated in serum-free medium that is tissue specific, species specific, and continuously available. Methods. Primary explant cultures from human cadaver donor corneas were generated and subsequently infected with Adeno 12-SV40 (Ad12-SV40) hybrid virus or transfected with plasmid RSV-T. Results. Several lines of human corneal epithelial cells with extended life spin were developed and characterized. Propagation of both primary cultures and lines with extended life span, upon collagen membranes at an air-liquid interface, promoted multilayering, more closely approximating the morphology observed in situ. Conclusions. In vitro models, using primary cultures of corneal epithelium and lines of corneal epithelial cells with extended life span, retain a variety of phenotypic characteristics and may be used as an adjunct to ocular toxicology studies and as a tool to investigate corneal epithelial cell biology. C1 NATL CTR RES RESOURCES,BOSTON,MA. KEIMYUNG UNIV,DEPT ANAT,TAEGU,SOUTH KOREA. NIH,NATL CANC INST,BETHESDA,MD 20892. RP KAHN, CR (reprint author), GILLETTE MED EVALUAT LABS,401 PROFESS DR,GAITHERSBURG,MD 20879, USA. NR 26 TC 107 Z9 114 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 NOV PY 1993 VL 34 IS 12 BP 3429 EP 3441 PG 13 WC Ophthalmology SC Ophthalmology GA MF621 UT WOS:A1993MF62100024 PM 7693609 ER PT J AU KITAMURA, H GRAY, TE JETTEN, AM INAYAMA, Y NETTESHEIM, P AF KITAMURA, H GRAY, TE JETTEN, AM INAYAMA, Y NETTESHEIM, P TI ENHANCED GROWTH-POTENTIAL OF CULTURED RABBIT TRACHEAL EPITHELIAL-CELLS FOLLOWING EXPOSURE TO N-METHYL-N'-NITRO-N-NITROSOGUANIDINE SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE TRACHEAL EPITHELIAL CELL; RABBIT; CULTURE; CHEMICAL CARCINOGEN; ENHANCED GROWTH POTENTIAL ID NEOPLASTIC PROGRESSION; BASAL CELLS; DIFFERENTIATION; QUANTITATION; SUBSTRATUM; FREQUENCY; INVITRO; LUNG AB To establish a standardized model for the transformation of rabbit airway epithelial cells, we attempted to transform rabbit tracheal epithelial (RbTE) cells in culture with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). RbTE cells, harvested by enzymatic digestion from male New Zealand white rabbits, were plated onto feeder layers of irradiated 3T3 cells. Control cells proliferated exponentially during the 2nd week of culture and reached the plateau phase by the 3rd week. Cells exposed to MNNG (0.1 mug/ml) proliferated in a fashion similar to the control cells, except that there was some delay before proliferation began. The clonogenic activity of RbTE cells rapidly decreased in parallel with the increase in cell population equally in the control and MNNG groups. During the late plateau phase, cells exposed to MNNG regained clonogenic activity, and this compartment size expanded with time, whereas the clonogenic activity in control cultures remained below the detectable level. In RbTE cell cultures exposed three times to 0.1 mug/ml MNNG, large, persistent and proliferating colonies emerged at a frequency of 1.3 x 10(-2) among the surviving clones, whereas all the control cultures eventually became senescent. The MNNG-induced alteration in the growth potential of RbTE cells, i.e., the extended lifespan, and the maintenance and even expansion of clonogenic activity, was similar to that of transformed rat tracheal epithelial cells. However, no immortal cell line could be established from these growth-altered RbTE cells. We therefore concluded that the growth-altered RbTE cells were partially transformed. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. RP KITAMURA, H (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT PATHOL,ANAT & SURG PATHOL LAB,3-9 FUKUURA,KANAZAWA KU,YOKOHAMA 236,JAPAN. OI Jetten, Anton/0000-0003-0954-4445 NR 19 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD NOV PY 1993 VL 84 IS 11 BP 1113 EP 1119 PG 7 WC Oncology SC Oncology GA MH956 UT WOS:A1993MH95600005 PM 8276716 ER PT J AU ZONDERMAN, AB HERBST, JH SCHMIDT, C COSTA, PT MCCRAE, RR AF ZONDERMAN, AB HERBST, JH SCHMIDT, C COSTA, PT MCCRAE, RR TI DEPRESSIVE SYMPTOMS AS A NONSPECIFIC, GRADED RISK FOR PSYCHIATRIC DIAGNOSES SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID CATCHMENT-AREA PROGRAM; LIFE STRESS RESEARCH; EMPIRICAL-FINDINGS; MENTAL-DISORDERS; MAJOR DEPRESSION; PERSONALITY; PREVALENCE; COMMUNITY; EPIDEMIOLOGY; POPULATION AB Using data from a 16-year follow-up of a nationally representative sample of 6,913 adults, measures of depressive symptoms were used to predict psychiatric diagnoses taken from hospitalization records. In proportional hazards analyses, two measures of depression were significantly associated with subsequent diagnoses of depression and other psychiatric disorders after statistical control for demographic variables and previous history of psychological problems. Depressive symptoms predicted late as well as early occurrence of psychiatric diagnoses and showed a pattern of increasing risk with increasing scores, even below clinical cutoffs. This pattern of results is consistent with the view that depressive symptoms predict future psychiatric disorders largely because they serve as proxy measures of some chronic vulnerability, such as the normal personality dimension of neuroticism. C1 FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. RP ZONDERMAN, AB (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 NR 56 TC 38 Z9 38 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 1993 VL 102 IS 4 BP 544 EP 552 DI 10.1037/0021-843X.102.4.544 PG 9 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA MF719 UT WOS:A1993MF71900005 PM 8282922 ER PT J AU ARYA, SK SADAIE, MR AF ARYA, SK SADAIE, MR TI FUSOGENICITY OF MUTANT AND CHIMERIC PROVIRUSES DERIVED FROM MOLECULAR CLONES OF CYTOPATHIC AND NONCYTOPATHIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-2 PROVIRUS EXPRESSION; SYNCYTIA INDUCTION; CYTOPATHIC AND NONCYTOPATHIC VARIANTS ID ENVELOPE GLYCOPROTEIN; NEF GENE; SYNCYTIUM FORMATION; PEPTIDE SEQUENCE; FUSION PEPTIDE; V3 DOMAIN; CD4; REPLICATION; PROTEIN; IDENTIFICATION AB Analysis of the phenotype of the molecular clones of cytopathic and fusogenic, noncytopathic and nonfusogenic, and chimeric proviruses of human immunodeficiency virus type 2 (HIV-2) suggests that the major determinant of the attenuated fusogenicity and cytopathicity of HIV-2 was located in the 3'-half of the genome, with envelope playing the more dominant role. However, no single linear domain within the envelope, including the major CD4 binding domain and fusogenic domain, was sufficient by itself for syncytia induction and cytopathic effects. Truncation of the transmembrane envelope glycoprotein downstream of the transmembrane region was not a major factor in this regard. However, truncation within the transmembrane region rendered the provirus replication incompetent. The regulatory genes (tat, rev) and auxiliary gene (nef) did not seem to play a critical role in determining HIV-2 fusogenicity in vitro. The results suggest the importance of the overall conformation of the envelope in the divergent phenotypes of HIV-2. RP ARYA, SK (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892, USA. NR 38 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD NOV PY 1993 VL 6 IS 11 BP 1205 EP 1211 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MC830 UT WOS:A1993MC83000004 PM 8229655 ER PT J AU IGARASHI, Y SKONER, DP DOYLE, WJ WHITE, MV FIREMAN, P KALINER, MA AF IGARASHI, Y SKONER, DP DOYLE, WJ WHITE, MV FIREMAN, P KALINER, MA TI ANALYSIS OF NASAL SECRETIONS DURING EXPERIMENTAL RHINOVIRUS UPPER RESPIRATORY-INFECTIONS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ALLERGIC RHINITIS; NASAL SECRETION; GLANDULAR SECRETION; RHINOVIRUS; VASCULAR PERMEABILITY ID HISTAMINE-RELEASING ACTIVITY; PATHO-PHYSIOLOGY; MAST-CELLS; MEDIATOR RELEASE; RHINITIS; PROTEIN; BRADYKININ; MUCOSA; COLDS; MUCUS AB Background: To determine the underlying mechanisms for rhinovirus-induced nasal secretions, nasal lavage fluids were analyzed during experimental rhinovirus infections. Methods: Twenty patients with allergic rhinitis and 18 nonallergic control subjects were inoculated with rhinovirus type 39. Nasal lavage was performed before and on days 2 through 7 after viral inoculation, and the lavage fluids were assayed for proteins and mast cell mediators. Results: The secretion of total protein and both plasma proteins (albumin and IgG) and glandular proteins (lactoferrin, lysozyme, and secretory IgA) increased after rhinovirus inoculation. Analysis of the specific protein constituents revealed that nasal secretions during the initial response to the rhinovirus infection were predominantly due to increased vascular permeability. Allergic subjects tended to have fewer symptoms and more vascular permeability than control subjects, and increased histamine secretion after rhinovirus inoculation was more frequently seen in the allergy group. Conclusion: Nasal secretions found early in the course of a viral upper respiratory infection are due to increased vascular permeability, whereas glandular secretions predominate later in the infection. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,CHILDRENS HOSP PITTSBURGH,DEPT OTOLARYNGOL,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,CHILDRENS HOSP PITTSBURGH,DEPT ALLERGY IMMUNOL & RHEUMATOL,PITTSBURGH,PA 15261. FU NCRR NIH HHS [MO1RR00084]; NIAID NIH HHS [AI19262] NR 53 TC 80 Z9 82 U1 0 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 NOV PY 1993 VL 92 IS 5 BP 722 EP 731 DI 10.1016/0091-6749(93)90016-9 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA MG982 UT WOS:A1993MG98200014 PM 8227864 ER PT J AU SINGH, K DEONARINE, D SHANMUGAM, V SENGER, DR MUKHERJEE, AB CHANG, PL PRINCE, CW MUKHERJEE, BB AF SINGH, K DEONARINE, D SHANMUGAM, V SENGER, DR MUKHERJEE, AB CHANG, PL PRINCE, CW MUKHERJEE, BB TI CALCIUM-BINDING PROPERTIES OF OSTEOPONTIN DERIVED FROM NONOSTEOGENIC SOURCES SO JOURNAL OF BIOCHEMISTRY LA English DT Article ID SECRETED PHOSPHOPROTEIN-I; BONE EXTRACELLULAR-MATRIX; RAT-KIDNEY CELLS; NEOPLASTIC TRANSFORMATION; PHYSIOLOGICAL-PROPERTIES; NONPHOSPHORYLATED FORMS; CA-45 AUTORADIOGRAPHY; CA2+-BINDING PROTEINS; EXPRESSION; SIALOPROTEIN AB Osteopontin (OP), purified from rat bone, binds Ca2+ but whether different molecular forms of OPs derived from non-osteogenic sources and non-phosphorylated OP also possess this property remains to be determined. Furthermore, it is not known which specific site or sites of the molecule bind Ca2+. In the present study, following an established procedure, total proteins in the conditioned media from OP-synthesizing cell cultures were separated by SDS-PAGE, transferred to Immobilon-P membranes, and incubated with (CaCl2)-Ca-45, then Ca2+ ions bound to protein bands were analyzed by autoradiography. Purified OPs, and synthetic oligopeptides representing specific domains of the OP molecule were adsorbed on the membrane and processed as described above. Our results show that OPs synthesized by normal rat kidney cells, oncogenically transformed Rat-1 cells, OP purified from human milk, and non-phosphorylated OP secreted by 1(alpha),25-dihydroxyvitamin D-3-treated mouse epidermal JB6 cells all bind detectable levels of Ca2+ with specificity. We also show that a synthetic peptide representing the domain of OP which contains nine consecutive aspartic acid residues binds Ca2+ with specificity. It is probable, therefore, that a Ca2+-binding site resides in this region of the OP molecule. We conclude that Ca2+-binding is a general property of OP, irrespective of its molecular mass and origin, and the phosphate moieties of OP may not influence the conformation or accessibility of the Ca2+ affinity sites of the molecule. C1 MCGILL UNIV,DEPT BIOL,MONTREAL H3A 1B1,PQ,CANADA. MCGILL UNIV,CTR HUMAN GENET,MONTREAL H3A 1B1,PQ,CANADA. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294. FU NCI NIH HHS [CA34025]; NIDCR NIH HHS [DE06739, DE00247] NR 31 TC 46 Z9 47 U1 0 U2 3 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD NOV PY 1993 VL 114 IS 5 BP 702 EP 707 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF309 UT WOS:A1993MF30900014 PM 8113224 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI MEASUREMENT OF AMIDE PROTON-EXCHANGE RATES AND NOES WITH WATER IN C-13/N-15-ENRICHED CALCINEURIN-B SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE HYDROGEN EXCHANGE; NOESY; ROESY; WATER; PROTEIN; 2D-NMR; CALCINEURIN-B ID 2-DIMENSIONAL NMR-SPECTROSCOPY; AQUEOUS-SOLUTION; PROTEIN HYDRATION; INTERNAL WATER; BOUND WATER; 2D NMR; HETERONUCLEAR; CALMODULIN; MOLECULES; SPECTRA AB A rapid and sensitive 2D approach is presented for measuring amide proton exchange rates and the NOE interaction between amide protons and water. The approach is applicable to uniformly C-13/N-15-enriched proteins and can measure magnetization exchange rates in the 0.02 to > 20 s-1 range. The experiments rely on selective excitation of the water resonance, coupled with purging of underlying H(alpha) resonances, followed by NOESY- or ROESY-type transfer to amide protons, which are dispersed by the amide N-15 frequencies in an HSQC-type experiment. Two separate but interleaved experiments, with and without selective inversion of the H2O resonance, yield quantitative results. The method is demonstrated for a sample of the calcium-binding protein calcineurin B. Results indicate rapid amide exchange for the five calcineurin B residues that are analogous to the five rapidly exchanging residues in the 'central helix' of the homologous protein calmodulin. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 32 TC 152 Z9 152 U1 0 U2 4 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 1993 VL 3 IS 6 BP 627 EP 638 PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA MK830 UT WOS:A1993MK83000002 PM 8111229 ER PT J AU WANG, AC BAX, A AF WANG, AC BAX, A TI MINIMIZING THE EFFECTS OF RADIOFREQUENCY HEATING IN MULTIDIMENSIONAL NMR EXPERIMENTS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE RADIOFREQUENCY HEATING; LINE-SHAPE DISTORTION; MULTIDIMENSIONAL NMR; TEMPERATURE; DECOUPLING; ISOTROPIC MIXING ID MAGNETIZATION TRANSFER; CROSS POLARIZATION; AQUEOUS-SOLUTIONS; SPECTROSCOPY; SAMPLES; LIQUIDS; C-13; SPECTROMETERS; PROTEINS AB Application of radio-frequency power in multidimensional NMR experiments can significantly increase the sample temperature compared to that of the surrounding gas flow. Radio-frequency heating effects become more severe at higher magnetic field strengths and ionic strengths. The effects are particularly noticeable for experiments that utilize H-1 and/or C-13 isotropic mixing and broadband decoupling. If radio-frequency power is applied during the systematically increasing evolution period t1, the sample temperature can change with t, and thereby cause line-shape distortions. Such distortions are easily avoided by ensuring that the average radio-frequency power remains constant during the entire experiment. RP WANG, AC (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 21 TC 68 Z9 69 U1 0 U2 8 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 1993 VL 3 IS 6 BP 715 EP 720 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA MK830 UT WOS:A1993MK83000008 PM 8111234 ER PT J AU REHM, S DEVOR, DE AF REHM, S DEVOR, DE TI ACUTE EFFECTS OF 4-IPOMEANOL ON EXPERIMENTAL LUNG-TUMORS WITH BRONCHIOLAR OR ALVEOLAR CELL FEATURES IN SYRIAN-HAMSTERS OR C3H/HENCR MICE SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE 4-IPOMEANOL; LUNG CANCER; ALVEOLAR CELL; CLARA CELL; HISTOGENESIS ID CLARA CELL; METABOLIC-ACTIVATION; MOUSE LUNG; PULMONARY NEOPLASMS; COVALENT BINDING; II CELLS; TOXICITY; LESIONS; HISTOGENESIS; EPITHELIUM AB 4-Ipomenaol (IPO) has been shown to induce P-450-mediated necrosis of Clara cells in experimental animals, and clinical trials were initiated to treat people with bronchioloalveolar cancers with this novel drug. We therefore performed experiments to examine two different animal lung tumor models for acute IPO cytotoxicity: hamster Clara-cell-derived adenocarcinomas and mouse alveolar type II cell tumors. Clara cells serve as stem cells for airway cell renewal and, therefore, tumors derived from Clara cells may likewise differentiate into various bronchiolar cell types, or undergo squamous cell metaplasia. Bronchiolar cell tumors were induced in Syrian hamsters by a single weekly gavage with 6.8 mg N-nitrosomethyl-n-heptylamine (NMHA)/animal for 35 weeks. NMHA-induced bronchiolar tumors were classified as well-differentiated lepidic bronchioloalveolar carcinomas, acinar adenocarcinoma, adenosquamous carcinoma, and squamous-cell carcinoma. After 35 and 46 experimental weeks, control and carcinogen-treated hamsters were injected once with doses of 40-110 mg IPO/kg i.p. and necropsied 15-48 h later. Solid and papillary tumors with alveolar cell features were induced transplacentally in C3H/HeNCr mice, by treating pregnant animals on gestation day 16 with 0.5 mmol N-nitrosoethylurea/kg, i.p. Offspring of control and carcinogen-treated mice were injected at 2-3 months of age with 35 mg or 50 mg IPO/kg i.p. and necropsied either 24-48 h or 5 and 12 days after injection. Light microscopic studies were carried out to assess cytotoxic effects in various tissues in both hamsters and mice; in hamsters, additional ultrastructural studies were performed. When administered to hamsters, IPO induced moderate to severe cytotoxicity in normal and dysplastic bronchiolar lining cells, in most lepidic bronchioloalveolar carcinomas, and in some glandular areas of adenosquamous cell carcinomas. Susceptible cells included normal, anaplastic, and neoplastic nonciliated and some ciliated bronchiolar cells. Undifferentiated and squamous tumor cells were resistant to IPO, as were resident normal alveolar type II cells. However, some adenocarcinomas composed primarily of ciliated and mucous cells also showed no IPO-induced necrosis, indicating a deficiency in appropriate activating enzymes. In the mice, IPO induced bronchiolar cell necrosis and, at the high dose, also severe pulmonary edema. No cytotoxicity was observed in normal or hyperplastic alveolar epithelium, nor in either solid or papillary growth forms of mouse alveolar cell tumors. In conclusion, these experiments show, in original tumor settings of the lung, that it is possible to achieve cell-specific cytotoxic effects based on cellular composition and functional maturity, i.e., toxicity in carcinomas of predominantly nonciliated bronchiolar cells but not in tumors of alveolar type II cell lineage. RP REHM, S (reprint author), NCI,FCRDC,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FCRDC BLDG 538,ROOM 220,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 49 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD NOV-DEC PY 1993 VL 120 IS 1-2 BP 41 EP 50 DI 10.1007/BF01200723 PG 10 WC Oncology SC Oncology GA MD995 UT WOS:A1993MD99500008 PM 8270607 ER PT J AU ROSKAMS, AJI FRIEDMAN, V WOOD, CM WALKER, L OWENS, GA STEWART, DA ALTUS, MS DANNER, DB LIU, XT MCCLUNG, JK AF ROSKAMS, AJI FRIEDMAN, V WOOD, CM WALKER, L OWENS, GA STEWART, DA ALTUS, MS DANNER, DB LIU, XT MCCLUNG, JK TI CELL-CYCLE ACTIVITY AND EXPRESSION OF PROHIBITION MESSENGER-RNA SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RETINOBLASTOMA PROTEIN; GROWTH-REGULATION; GENE; KINASE; P53; PHOSPHORYLATION; SUPPRESSION; FIBROBLASTS; CANCER; CDC2 AB Prohibitin, a novel intracellular antiproliferative protein, blocks entry into the S phase of the cell division cycle when its mRNA is microinjected into normal fibroblasts or HeLa cells. To learn more about the interaction between prohibitin and the cell cycle, we studied the effect of microinjecting prohibitin mRNA at different points during the transition from G0 to S phase and analyzed prohibitin mRNA and protein levels in different parts of the cell cycle. The antiproliferative activity of microinjected prohibitin mRNA is high in G0/G1 and falls as cells approach S phase. Prohibitin mRNA and protein levels are high in G1, fall with S phase, rise again in G2, and fall in M. Together, these findings suggest that endogenous prohibitin contributes to the control of the G, to S transition in cycling cells in a complex manner, which involves both a transcriptional and posttranslational mechanism. (C) 1993 Wiley-Liss, Inc. C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. SAMUEL ROBERTS NOBLE FDN INC,DIV BIOMED,ARDMORE,OK 73402. NR 24 TC 63 Z9 66 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1993 VL 157 IS 2 BP 289 EP 295 DI 10.1002/jcp.1041570211 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ME671 UT WOS:A1993ME67100010 PM 8227162 ER PT J AU MURPHY, AN UNSWORTH, EJ STETLERSTEVENSON, WG AF MURPHY, AN UNSWORTH, EJ STETLERSTEVENSON, WG TI TISSUE INHIBITOR OF METALLOPROTEINASES-2 INHIBITS BFGF-INDUCED HUMAN MICROVASCULAR ENDOTHELIAL-CELL PROLIFERATION SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; HUMAN AMNIOTIC MEMBRANE; IV COLLAGENASE; INTERSTITIAL COLLAGENASE; FIBROBLAST COLLAGENASE; TUMOR INVASION; GROWTH-FACTOR; CDNA CLONING; EXPRESSION; TIMP-2 AB Tissue inhibitor of metalloproteinase-2 (TIMP-2), a protease inhibitor that binds to the latent and active forms of 72 kDa type IV collagenase (gelatinase A), was found to inhibit the in vitro proliferation of human microvascular endothelial (HME) cells stimulated with bFGF and 5% serum. The maximal inhibitory effect of TIMP-2 on incorporation of H-3-thymidine was evident 24 hours after bFGF stimulation of these cells and ranged between 45 and 60%. The half-maximal effective concentration of TIMP-2 was 107 +/- 12 nM (S.D.). In contrast, TIMP-1 was not found to slow the growth of HME cells. The inhibition of cell proliferation observed with TIMP-2 was not mimicked by addition to the culture medium of BB94, a general matrix metalloproteinase inhibitor, nor antibodies to the 72 kDa type IV collagenase. In addition to growth, two other cell functions associated with the angiogenic process were tested for sensitivity to TIMP-2. Cell adhesion to tissue culture plastic was slightly stimulated by TIMP-2, and cell migration was inhibited with short-term exposure to TIMP-2, but neither process was affected by longer-term exposure. The ability of TIMP-2 to inhibit cultured endothelial cell proliferation independent of protease inhibitory activity suggests that TIMP-2 may have additional actions which may limit neovascularization associated with solid tumor growth and metastasis in vivo. (C) 1993 Wiley-Liss, Inc. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 43 TC 286 Z9 302 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1993 VL 157 IS 2 BP 351 EP 358 DI 10.1002/jcp.1041570219 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ME671 UT WOS:A1993ME67100018 PM 7693724 ER PT J AU VOGEL, T BLAKE, DA WHIKEHART, DR GUO, NH ZABRENETZKY, VS ROBERTS, DD AF VOGEL, T BLAKE, DA WHIKEHART, DR GUO, NH ZABRENETZKY, VS ROBERTS, DD TI SPECIFIC SIMPLE SUGARS PROMOTE CHEMOTAXIS AND CHEMOKINESIS OF CORNEAL ENDOTHELIAL-CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; FACTOR RECEPTORS; FLUID TRANSPORT; PROLIFERATION; STIMULATION; CULTURE; GLUCOSE; INVITRO; ATPASE; NA+ AB Bovine corneal endothelial cells showed a strong migratory response to specific simple sugars (D-glucose and sucrose, but not L-glucose, sorbitol, lactose, or D-galactose) at concentrations above 10 mM. Checkerboard analysis of the migratory responses in modified Boyden chambers indicated both chemotactic and chemokinetic effects. Serum starvation of the cultures increased the chemotaxis towardS D-glucose and 2-deoxy-D-glucose, but not towards sucrose. Migration to sucrose and glucose was inhibited by chelation of extracellular calcium or by inhibition of Na+,K+ ATPase with ouabain. To date, this migratory response has been found only in corneal endothelial cells. Neither human melanoma cells, human breast carcinoma cells, bovine aortic endothelial cells, nor bovine microvascular endothelial cells migrated towards simple sugars, although all cell types migrated toward fibronectin in chemotaxis assays. After 16-19 passages in culture, bovine corneal endothelial cells retained their ability to migrate towards fibronectin, but lost their ability to migrate towards sugars. This loss of migratory response was accompanied by a sevenfold decrease in Na+,K+ ATPase activity. Although loss of Na+,K+ ATPase activity accompanied the loss of migratory response, pretreatment of cell cultures with 25 mM glucose did not stimulate, but rather lowered Na+,K+ ATPase activity in low or high passage cultures. (C) 1993 Wiley-Liss, Inc. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. MEHARRY MED COLL,DEPT BIOCHEM,NASHVILLE,TN 37208. UNIV ALABAMA,SCH OPTOMETRY,VIS SCI RES CTR,BIRMINGHAM,AL 35294. BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NEI NIH HHS [NEI EY02949, NEI EY09092] NR 34 TC 9 Z9 9 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 NOV PY 1993 VL 157 IS 2 BP 359 EP 366 DI 10.1002/jcp.1041570220 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ME671 UT WOS:A1993ME67100019 PM 8227167 ER PT J AU BROCK, MA CHREST, F AF BROCK, MA CHREST, F TI DIFFERENTIAL REGULATION OF ACTIN POLYMERIZATION FOLLOWING ACTIVATION OF RESTING T-LYMPHOCYTES FROM YOUNG AND AGED MICE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID LIGAND-INDUCED ASSOCIATION; PROTEIN-KINASE-C; CYTOCHALASIN-B; CYTOSKELETAL MATRIX; BINDING-PROTEINS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; MURINE LYMPHOCYTES; MEMBRANE-PROTEINS; HUMAN-NEUTROPHILS; RECEPTOR COMPLEX AB Actin polymerization accompanies receptor-mediated responses and is correlated with motility-related events. In T lymphocytes, there is a lateral redistribution of surface receptors into caps and aggregation of actin-myosin in cytoplasmic sub-caps, and these are impaired in T cells from aged individuals. This study documents marked changes in age-related cytoskeletal actin filament function which may account for the reduced motility. Basal levels of filamentous actin (F-actin) are significantly higher in purified G, T cells from aged C57BL/6 mice, due to a preferential increase in the CD8+ subpopulation. Following activation of the resting T cells with Concanavalin A (Con A), F-actin depolymerized in cells from young mice for 2 min, followed by rapid polymerization, reaching a plateau 200% above resting levels. In cells from 15-17-month-old mice, an attenuated depolymerization phase was seen for 45 sec, followed by little polymerization. No depolymerization or polymerization phases occurred in cells from aged mice. Phorbol 12 myristate 13-acetate (PMA), which activates protein kinase C (PKC), bypassing receptor mediated signals, induced actin polymerization to 57% of the levels of that after Con A stimulation in cells from both young and old animals and partially eliminated the differences in actin filament assembly due to age. Perturbation of the cytoskeleton with cytochalasin E (CE) potentiated proliferation of Con A-stimulated T cells from aged mice but did not completely restore the deficit attributed to immunosenescence. The results show an age-related impairment of cytoskeletal functions and suggest that differences in early signal transduction events contribute to the decrements in surface receptor motility and subsequent proliferation of T lymphocytes from older individuals. (C) 1993 Wiley-Liss, Inc. RP BROCK, MA (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 75 TC 20 Z9 22 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 NOV PY 1993 VL 157 IS 2 BP 367 EP 378 DI 10.1002/jcp.1041570221 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ME671 UT WOS:A1993ME67100020 PM 8227168 ER PT J AU SUN, Y DEIBLER, GE SMITH, CB AF SUN, Y DEIBLER, GE SMITH, CB TI EFFECTS OF AXOTOMY ON PROTEIN-SYNTHESIS IN THE RAT HYPOGLOSSAL NUCLEUS - EXAMINATION OF THE INFLUENCE OF LOCAL RECYCLING OF LEUCINE DERIVED FROM PROTEIN-DEGRADATION INTO THE PRECURSOR POOL SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE LEUCINE RECYCLING; PROTEIN SYNTHESIS; REGENERATION; BRAIN; HYPOGLOSSAL AXOTOMY ID CEREBRAL GLUCOSE-UTILIZATION; SYNTHESIS INVIVO; REGIONAL RATES; AMINO-ACIDS; BRAIN AB The quantitative autoradiographic L-[1-C-14] leucine method for the determination of regional rates of cerebral protein synthesis (ICPS(leu)) requires knowledge of the degree of recycling of leucine derived from protein degradation into the precursor pool for protein synthesis, which can be evaluated by measuring lambda(i), the steady-state ratio of the leucine-specific activity in the precursor amino acid pool (tRNA-bound leucine) to that of the arterial plasma. To define the changes in ICPS(leu) during regeneration of the hypoglossal nerve, we examined the effects of axotomy on the value of lambda(i). Because the concentration of tRNA-bound leucine in the hypoglossal nucleus is too low to measure, we measured the equivalent ratio for the total acid-soluble pool (psi(i)) and applied the linear relationship between lambda and psi found in the whole brain to calculate a value of lambda(i) in the ipsilateral and contralateral hypoglossal nuclei of 22 adult female rats 2, 18, 35, and 60 days after unilateral hypoglossal axotomy. Statistically significant but quantitatively inconsequential effects of axotomy on values of psi(i) and lambda(i) were found. Therefore, the mean value for lambda(i)(0.64) of the left and right hypoglossal nuclei in all 22 axotomized rats was used to calculate ICPS(leu). In a separate group of 15 unilaterally axotomized rats, ICPS(leu) was determined by the autoradiographic technique; ICPS(leu) was increased on the axotomized side by 23% on day 2, 30% on day 18, and 13% on day 35. By postaxotomy day 60, ICPS(leu) had returned to normal. C1 US PHS,NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 18 TC 11 Z9 11 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 NOV PY 1993 VL 13 IS 6 BP 1006 EP 1012 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MC445 UT WOS:A1993MC44500014 PM 8408308 ER PT J AU CLARK, C CARSON, R AF CLARK, C CARSON, R TI ANALYSIS OF COVARIANCE IN STATISTICAL PARAMETRIC MAPPING SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Letter C1 NIH,DEPT PET,BETHESDA,MD 20892. RP CLARK, C (reprint author), UNIV BRITISH COLUMBIA,DEPT PSYCHIAT,VANCOUVER V6T 1W5,BC,CANADA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 1 TC 10 Z9 10 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 NOV PY 1993 VL 13 IS 6 BP 1038 EP 1038 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MC445 UT WOS:A1993MC44500020 PM 8408314 ER PT J AU RANDOLPH, C GOLD, JM CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR AF RANDOLPH, C GOLD, JM CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR TI IMPLICIT MEMORY IN PATIENTS WITH SCHIZOPHRENIA AND NORMAL CONTROLS - EFFECTS OF TASK DEMANDS ON SUSCEPTIBILITY TO PRIMING SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID EXPLICIT MEMORY; ALZHEIMERS-DISEASE; RECOGNITION MEMORY; ASSOCIATIONS; INDEPENDENCE; INFORMATION; COMPLETION; AMNESIA; TESTS AB Two experiments employing a stem-completion priming paradigm are reported. The first of these compared patients with schizophrenia (SC) to normal controls and demonstrated impaired implicit memory in the SC patients under task conditions identical to those used previously with other patient groups. The second experiment was designed to examine the effects of implicit task demands and stimulus selection upon susceptibility to priming, with a second group of SC patients and normal controls. Results indicated that the ability to carry out the task demands of the implicit condition (i.e., generate completions for word-stems) was inversely related to susceptibility to priming in both the SC patients and controls. In addition, the baseline probability of specific completions was found to be correlated with the ease of priming those completions, suggesting a possible mechanism for producing statistical dissociations between implicit and explicit retrieval conditions with this paradigm. These findings suggest that certain implicit tasks may be susceptible to nonmemory psychological influences that have not been adequately investigated to date; these may be responsible for ''normalizing'' the performance of amnesic patients as well as producing statistical dissociations from explicit memory tasks. C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD. RP RANDOLPH, C (reprint author), NINCDS,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 5C104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 24 Z9 24 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD NOV PY 1993 VL 15 IS 6 BP 853 EP 866 DI 10.1080/01688639308402603 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA MM923 UT WOS:A1993MM92300002 PM 8120123 ER PT J AU CASEY, BJ GORDON, CT MANNHEIM, GB RUMSEY, JM AF CASEY, BJ GORDON, CT MANNHEIM, GB RUMSEY, JM TI DYSFUNCTIONAL ATTENTION IN AUTISTIC SAVANTS SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID CHILDREN; INDIVIDUALS; COMPONENTS; DEFICITS AB A dysfunctional attention hypothesis of the basis of savant skills was tested with a series of computerized tasks that assessed the ability to divide, shift, direct, and sustain attention. Ten healthy men with pervasive developmental disorders and unusual calendar-calculating skill, and 10 age- and sex-matched controls were tested. There were four general findings. First, the savants and controls did not differ on a measure of visual sustained attention. Second, the savants failed to detect rare auditory targets significantly more than did the controls. Third, the savants were unable to efficiently divide their attention when required to detect both visual and auditory targets simultaneously. Finally, deficient orienting or a deficit in shifting selective attention from one stimulus location to another was evidenced in overall slower reaction times for the savants across tasks requiring shifts and redirecting of attention. This deficit was attributed to an inability to disengage attention as a result of deficient orienting and overselectivity. RP CASEY, BJ (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 102 Z9 103 U1 0 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD NOV PY 1993 VL 15 IS 6 BP 933 EP 946 DI 10.1080/01688639308402609 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA MM923 UT WOS:A1993MM92300008 PM 8120129 ER PT J AU EASTMAN, RC SIEBERT, CW HARRIS, M GORDEN, P AF EASTMAN, RC SIEBERT, CW HARRIS, M GORDEN, P TI CLINICAL REVIEW .51. IMPLICATIONS OF THE DIABETES CONTROL AND COMPLICATIONS TRIAL SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID RETINOPATHY RP EASTMAN, RC (reprint author), NIDDKD, DIV DIABET ENDOCRINOL & METAB DIS, BLDG 31, ROOM 9A-16, BETHESDA, MD 20892 USA. NR 14 TC 45 Z9 48 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1105 EP 1107 DI 10.1210/jc.77.5.1105 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600001 PM 8077299 ER PT J AU HIDAKA, A OKAJIMA, F BAN, T KOSUGI, S KONDO, Y KOHN, LD AF HIDAKA, A OKAJIMA, F BAN, T KOSUGI, S KONDO, Y KOHN, LD TI RECEPTOR CROSS-TALK CAN OPTIMIZE ASSAYS FOR AUTOANTIBODIES TO THE THYROTROPIN RECEPTOR - EFFECT OF PHENYLISOPROPYLADENOSINE ON ADENOSINE-3',5'-MONOPHOSPHATE AND INOSITOL PHOSPHATE LEVELS IN RAT FRTL-5 THYROID-CELLS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CYCLIC-AMP; IMMUNOGLOBULIN-G; PHOSPHOLIPASE-C; PERTUSSIS TOXIN; IODIDE EFFLUX; TSH RECEPTOR; STIMULATING IMMUNOGLOBULINS; PHOSPHOINOSITIDE TURNOVER; GRAVES-DISEASE; GROWTH AB Immunoglobulins (IgG) from patients with Graves' disease increase inositol phosphate (IP) as well as cAMP production in rat thyroid FRTL-5 cells; IgGs from normal control subjects do not. Graves' IgG- and TSH-induced IP formation is inhibited by blocking TSH receptor (TSHR) antibodies from hypothyroid patients with primary myxedema, as is the cAMP response; this suggests that the Graves' IgG are acting through the TSHR to induce both the cAMP and phosphatidylinositol 4,5-biphosphate signal cascades in FRTL-5 thyroid cells as in cells with recombinant TSHR. Optimal conditions for measuring the Graves' IgG-induced IP increase include a NaCl-free Hanks' Balanced Salt Solution (HBSS) buffer system and a P-1 purinergic receptor agonist; the action of each is additive. Optimization by NaCl-free HBSS is similar to that observed in cAMP assays and is specific for TSH or Graves' IgG; thus, NaCl-free HBSS did not affect ATP-induced, and actually inhibited norepinephrine-induced, IP production in FRTL-5 cells. The P-1 purinergic receptor agonist acts via receptor cross-talk, which also allows further optimization of cAMP assays. Thus, adenosine deaminase improves Graves' IgG-induced cAMP production by removing adenosine from the medium. Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost. C1 GUNMA UNIV, INST ENDOCRINOL, DEPT PHYS BIOCHEM, MAEBASHI, GUNMA 371, JAPAN. NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NR 42 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1164 EP 1169 DI 10.1210/jc.77.5.1164 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600012 PM 8077307 ER PT J AU SHEMER, J YARON, A WERNER, H SHAO, ZM SHEIKH, MS FONTANA, JA LEROITH, D ROBERTS, CT AF SHEMER, J YARON, A WERNER, H SHAO, ZM SHEIKH, MS FONTANA, JA LEROITH, D ROBERTS, CT TI REGULATION OF INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING PROTEIN-5 IN THE T47D HUMAN BREAST-CARCINOMA CELL-LINE BY IGF-I AND RETINOIC ACID SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CANCER-CELLS; GENE-EXPRESSION; FIBROBLASTS; RECEPTORS; IDENTIFICATION; SECRETION AB The T47D human breast carcinoma cell line has been shown to synthesize insulin-like growth factor-I (IGF-I) binding proteins (IGFBPs) and IGF-I receptors, and to exhibit a mitogenic response to exogenous IGF-I. We have used T47D cells to investigate the regulation of IGFBPs by IGF-I and retinoic acid (RA), agents that affect cell proliferation and have been shown to regulate IGFBP levels in other cell types. Exposure of T47D cells to IGF-I resulted in the appearance of IGFBP-2, -4, and -5 in conditioned medium but had no effect on the levels of IGFBPs in Triton X-100-extracted cells. This effect was most pronounced for IGFBP-5 and was also elicited by an IGF-I analog that retains affinity for IGFBPs but not by insulin or IGF analogs that have decreased affinity for IGFBPs. Additionally, this effect was not associated with a change in IGFBP-5 messenger RNA (mRNA) levels; however, the appearance of IGFBP-5 in the conditioned medium was inhibited by an anti-IGF-I receptor antibody (alpha IR-3). RA decreased IGFBP-5 mRNA levels and cell-associated IGFBP-5 in both the presence and absence of IGF-I and inhibited the IGF-I-stimulated secretion of IGFBP-5 into T47D cell conditioned medium. These results suggest that IGF-I increases IGFBP-5 levels in the T47D cell line both through direct interaction with IGFBP-5 as well as through a receptor-mediated process that does not require direct interaction with IGFBPs. The latter results are consistent with an effect of IGF-I on a factor that may modulate an IGFBP protease activity. The inhibitory effect of RA, on the other hand, appears to be due primarily to regulation of IGFBP-5 mRNA levels. Thus, IGFBP-5 accumulation appears to be positively regulated by IGF-I, potentially at the level of susceptibility to proteolysis, and negatively regulated at the level of gene expression by RA. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. UNIV MARYLAND, VET ADM MED CTR, BALTIMORE, MD 21202 USA. OI Fontana, Joseph/0000-0003-3829-3358; Roberts, Charles/0000-0003-1756-5772 NR 34 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1246 EP 1250 DI 10.1210/jc.77.5.1246 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600026 PM 7521344 ER PT J AU NIEMAN, LK OLDFIELD, EH WESLEY, R CHROUSOS, GP LORIAUX, DL CUTLER, GB AF NIEMAN, LK OLDFIELD, EH WESLEY, R CHROUSOS, GP LORIAUX, DL CUTLER, GB TI A SIMPLIFIED MORNING OVINE CORTICOTROPIN-RELEASING HORMONE STIMULATION TEST FOR THE DIFFERENTIAL-DIAGNOSIS OF ADRENOCORTICOTROPIN-DEPENDENT CUSHINGS-SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; ECTOPIC ACTH SYNDROME; PITUITARY; DISORDERS; RESPONSES; DISEASE; CRF AB The objective of this study was to develop criteria for the interpretation of a morning ovine CRH stimulation test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Its design was retrospective review, and its setting was the in-patient unit of a tertiary care center. One hundred and eighteen patients with proven Cushing's disease or ectopic ACTH secretion were studied. The percent change in plasma ACTH and cortisol levels after CRH administration (1 mu g/ kg BW) was calculated for each patient using 3 combinations of pre-CRH values (-15, -10, -5, and -1 min) and 6 combinations of post-CRH values (15, 30, 45, and 60 min). The diagnostic performance of these 36 sets of response measures was compared. The mean ACTH concentrations 15 and 30 min after CRH increased by at least 35% above the mean basal value at -5 and -1 min in 93 of 100 patients with Cushing's disease, but in none of the 16 patients with ectopic ACTH secretion. This measure gave the best sensitivity (93%) and specificity (100%). The best cortisol criterion was a mean increase at 30 and 45 min of 20% or more above mean basal values at -5 and -1 min, which gave a sensitivity of 91% and a specificity of 88%. We developed a simplified diagnostic test with 100% specificity using ACTH measurements 5 and 1 min before and 15 and 30 min after CRH administration. Although all patients with ectopic ACTH secretion had less than a 35% increase in ACTH, the probability of Cushing's disease was high at all levels of response, indicating that other tests should be performed to confirm the diagnosis. C1 NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. RP NIEMAN, LK (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 23 TC 142 Z9 148 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1308 EP 1312 DI 10.1210/jc.77.5.1308 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600036 PM 8077325 ER PT J AU MUNICCHI, G ROSE, SR PESCOVITZ, OH BARNES, KM CASSORLA, FG CUTLER, GB AF MUNICCHI, G ROSE, SR PESCOVITZ, OH BARNES, KM CASSORLA, FG CUTLER, GB TI EFFECT OF DESLORELIN-INDUCED PUBERTAL DELAY ON THE GROWTH OF ADOLESCENTS WITH SHORT STATURE AND NORMALLY TIMED PUBERTY - PRELIMINARY-RESULTS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CENTRAL PRECOCIOUS PUBERTY; HORMONE-RELEASING HORMONE; LONG-TERM TREATMENT; SOMATIC GROWTH; ADULT HEIGHT; FINAL HEIGHT; CHILDREN; DEFICIENCY; THERAPY; AGONIST AB LH-releasing hormone agonist (LHRHa) treatment slows bone maturation and improves adult height in children with LHRH-dependent precocious puberty. To determine whether pubertal delay induced by LHRHa can enhance final height in patients with short stature and a normally timed puberty, we enrolled 43 short children (28 girls and 15 boys) in a double blind, placebo-controlled trial. Patients were assigned randomly to receive either placebo or LHRHa (deslorelin), administered sc at a dose of 4 mu g/kg.day for a period of 4 yr. This report describes the preliminary results in 16 children who have completed 4 yr of treatment (9 patients in the deslorelin group and 7 patients in the placebo group). Predicted adult height increased significantly in the deslorelin-treated patients, by 7.6 cm compared to the pretreatment baseline and by 10.3 cm compared to that in the placebo-treated patients (P < 0.005). Four of the 16 patients received concurrent GH treatment (3 among the deslorelin-treated patients and 1 among the placebo-treated patients). Omitting these patients from the analysis did not materially affect the results: predicted adult height in the deslorelin-treated patients increased by 7.2 cm compared to the pretreatment baseline and by 10.9 cm compared to that in the placebo-treated patients (P < 0.005). We conclude that pubertal delay induced by deslorelin significantly increases predicted adult height in adolescents with short stature and a normally timed puberty. Whether deslorelin treatment will increase the final height of these patients cannot be determined until they have stopped growing. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIV NEW MEXICO, DEPT PEDIAT, ALBUQUERQUE, NM 87131 USA. INDIANA UNIV, MED CTR, DEPT PEDIAT, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, MED CTR, DEPT PHYSIOL BIOPHYS, INDIANAPOLIS, IN 46202 USA. NR 24 TC 23 Z9 25 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1334 EP 1339 DI 10.1210/jc.77.5.1334 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600041 PM 8077329 ER PT J AU ELROEIY, A CHEN, XH ROBERTS, VJ LEROITH, D ROBERTS, CT YEN, SSC AF ELROEIY, A CHEN, XH ROBERTS, VJ LEROITH, D ROBERTS, CT YEN, SSC TI EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-II AND THE IGF-I, IGF-II AND INSULIN-RECEPTOR GENES AND LOCALIZATION OF THE GENE-PRODUCTS IN THE HUMAN OVARY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; HUMAN FOLLICULAR-FLUID; HUMAN GRANULOSA-CELLS; HORMONAL-REGULATION; AROMATASE-ACTIVITY; RNA; BINDING; IDENTIFICATION; FOLLICLES; STROMA AB We examined the expression of the genes encoding the insulin-like growth factors (IGFs) and their receptors (r) and the localization of their gene products in specific cellular compartments of the human ovary. mRNA was localized by in situ hybridization with specific human S-35-labeled antisense RNA probes, and protein was detected by immunocytochemistry with specific antisera. We studied 34 follicles (10 ovaries), which included both dominant and small antral follicles. In dominant follicles, no IGF-I mRNA was seen in either thecal or granulosa cells (GC), but IGF-Ir mRNA was expressed in GC. In contrast, abundant IGF-II mRNA was found exclusively in GC, whereas the IGF-IIr gene was expressed in both thecal cells and GC. Insulin receptor mRNA was widely distributed and expressed in all cell types, including stromal cells. Small antral follicles contained both IGF-I and IGF-II mRNA, which was restricted to thecal cells. Although IGF-Ir message was detected only in GC, IGF-IIr mRNA was expressed in both granulosa and thecal cells. As in dominant follicles, insulin receptor mRNA was found in thecal, granulosa, and stromal cells. No IGF-I immunoreactivity was seen in either dominant or small antral follicles; however, immunostaining for the other gene products demonstrated that each of these proteins colocalized with its corresponding mRNA. Thus, the relative distribution of ligand and receptor transcripts and protein in cellular compartments of the human ovary observed in this study supports the presence of an intraovarian IGF system and suggests that both autocrine and paracrine mechanisms of IGF action occur between GC and thecal cells. We conclude that 1) IGF-II, rather than IGF-I, is the principal IGF in human ovarian follicles, being synthesized in thecal cells in small antral follicles and in GC in dominant follicles; 2) in small antral follicles, IGF-II acts in an autocrine fashion in thecal cells and in a paracrine fashion in GC; 3) in dominant follicles, granulosa-derived IGF-II acts in an autocrine manner in GC; and 4) the presence of transcripts and proteins corresponding to the IGF and insulin receptors in cellular compartments of human ovaries may also provide target sites for the action of circulating ligands with a potential extraovarian role in the regulation of folliculogenesis. C1 UNIV CALIF SAN DIEGO, SCH MED, DEPT REPROD MED, LA JOLLA, CA 92093 USA. NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 FU NICHD NIH HHS [HD-07203-10, HD-12303-15] NR 42 TC 143 Z9 145 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1411 EP 1418 DI 10.1210/jc.77.5.1411 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600055 PM 8077342 ER PT J AU REINCKE, M KARL, M TRAVIS, W CHROUSOS, GP AF REINCKE, M KARL, M TRAVIS, W CHROUSOS, GP TI NO EVIDENCE FOR ONCOGENIC MUTATIONS IN GUANINE-NUCLEOTIDE-BINDING PROTEINS OF HUMAN ADRENOCORTICAL NEOPLASMS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID PITUITARY-TUMORS; ADENYLYL CYCLASE; DNA; GS; CHAIN; LINE; GENE AB G-Proteins are membrane-bound heterotrimeric polypeptides that couple receptor signals to second messenger systems such as cAMP. Recently, point mutations at 2 codons of the highly preserved alpha-chain of G(s), the adenyl cyclase-stimulating G-protein, were found in GH-secreting pituitary tumors. These mutations resulted in constitutively activated G(s) alpha and high intracellular cAMP levels. In addition, point mutations at similar codons of a different G-protein, G(i) alpha 2, were reported in adrenocortical neoplasms, suggesting a potential role of this isoform in the genesis of these tumors. We reevaluated the frequency of constitutively activating point mutations in the alpha-chain of the stimulatory (G(s) alpha) and inhibitory (G(i) alpha 2) G-proteins in human adrenocortical tumors. Seven adrenocortical carcinomas, 2 human adrenocortical tumor cell lines, and 11 adrenocortical adenomas were studied. Genomic DNA was purified from either frozen tumor tissue or paraffin-embedded sections. Using specific primers and the polymerase chain reaction, DNA fragments surrounding codons 201 and 227 (G(s) alpha) and 179 and 205 (G(i) alpha 2) were amplified and visualized on a 2% agarose gel. In a second asymmetric polymerase chain reaction, using nested primers, single stranded DNA was generated using 1-10 mu L of the initial amplification mixture and directly sequenced using the dideoxy chain termination method of Sanger. We found no mutations at codons 201, 227 and 179, 205 of G(s) alpha and G(i) alpha 2, respectively, in the tumors studied. We conclude that previously identified oncogenic point mutations in the stimulatory and inhibitory alpha-chain of G-proteins do not appear to be present at high frequency in adrenal neoplasms. Thus, the mechanism(s) of tumorigenesis in these tumors is different from that in GH-secreting adenomas and may involve oncogenic mutations of other cell constituents. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NCI, CLIN PATHOL BRANCH, BETHESDA, MD 20892 USA. NR 23 TC 63 Z9 65 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1993 VL 77 IS 5 BP 1419 EP 1422 DI 10.1210/jc.77.5.1419 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG136 UT WOS:A1993MG13600056 PM 8077343 ER PT J AU SHIMAKAWA, T BILD, DE AF SHIMAKAWA, T BILD, DE TI RELATIONSHIP BETWEEN HEMOGLOBIN AND CARDIOVASCULAR RISK-FACTORS IN YOUNG-ADULTS SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CARDIOVASCULAR DISEASE; DIET; HEMOGLOBIN ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; SERUM-CHOLESTEROL; BLOOD-VISCOSITY; UNITED-STATES; HEMATOCRIT; DEATH; MORTALITY; PRESSURE; CARDIA AB To understand mechanisms of association between hemoglobin and cardiovascular disease (CVD), the relationships between hemoglobin and CVD risk factors were examined in 5115 black and white men and women who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Hemoglobin was higher in men than women, whites than blacks, and smokers than non-smokers (p < 0.001). After adjusting for age, body mass index, current smoking status, and clinical center, hemoglobin correlated with diastolic blood pressure (0.11 less than or equal to r less than or equal to 0.22, p < 0.001) and plasma total cholesterol (0.08 less than or equal to r less than or equal to 0.11, p < 0.01) in all four race-sex groups and with systolic blood pressure in an but black women (0.07 less than or equal to r less than or equal to 0.13, p < 0.05). Among other factors possibly related to CVD risk, only serum albumin and white blood cell count showed significant correlations with hemoglobin in all groups (0.19 less than or equal to r less than or equal to 0.27, 0.07 less than or equal to r less than or equal to 0.18, respectively). These findings suggest that an association of hemoglobin with CVD risk factors may explain the association of hemoglobin with CVD. RP SHIMAKAWA, T (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 2C03,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 59 TC 28 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 1993 VL 46 IS 11 BP 1257 EP 1266 DI 10.1016/0895-4356(93)90090-N PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MG589 UT WOS:A1993MG58900007 PM 8229103 ER PT J AU PAHOR, M GURALNIK, JM GAMBASSI, G BERNABEI, R CAROSELLA, L CARBONIN, P AF PAHOR, M GURALNIK, JM GAMBASSI, G BERNABEI, R CAROSELLA, L CARBONIN, P TI THE IMPACT OF AGE ON RISK OF ADVERSE DRUG-REACTIONS TO DIGOXIN SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE DIGOXIN; ADVERSE DRUG REACTIONS; ELDERLY; HOSPITAL ADMISSION; PHARMACOEPIDEMIOLOGY; MULTIVARIATE ANALYSIS ID HEART-FAILURE; SERUM DIGOXIN; DIGITALIS INTOXICATION; SINUS RHYTHM; TOXICITY; REASSESSMENT; CROSSOVER; ADMISSION; REDUCTION; DISEASE AB To assess the association of age and other potential risk factors with digoxin. toxicity, adverse drug reactions to digoxin (ADRDIG) were studied in all patients (n = 1338) on digoxin therapy consecutively admitted to 41 clinical wards throughout Italy during 4 months in 1988. At the time of admission, 28 patients (2.1%) had evidence of ADRDIG. In multivariate logistic regression analysis, significant associations with ADRDIG were found for age greater than or equal to 80 years compared to age 65-79 years (OR = 2.75, 95% CI = 1.17-6.45), daily digoxin dosage of greater than or equal to 0.25 mg (OR = 2.51, 95% CI = 1.16-5.47), serum creatinine greater than or equal to 120 mu mol/L (OR = 3.75, 95% CI = 1.69-8.32), and for treatment with amiodarone, propafenone, quinidine or verapamil (OR = 2.60, 95% CI = 1.07-6.30). Those aged < 65 years had a similar risk of digoxin toxicity as those aged 65-79 years (OR = 1.07, 95% CI = 0.28-4.12). Adverse drug reactions to digoxin were found in 1 in 50 patients hospitalized on digoxin therapy. Patients aged 65-79 years were not at increased risk for digoxin toxicity compared to younger patients, while advanced age (greater than or equal to 80 years) was an independent risk factor for this outcome. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP PAHOR, M (reprint author), UNIV CATTOLICA SACRO CUORE,CATTEDRA GERONTOL,LGO F VITO 1,I-00168 ROME,ITALY. NR 43 TC 31 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 1993 VL 46 IS 11 BP 1305 EP 1314 DI 10.1016/0895-4356(93)90099-M PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MG589 UT WOS:A1993MG58900016 PM 8229108 ER PT J AU PERI, A CORDELLAMIELE, E MIELE, L MUKHERJEE, AB AF PERI, A CORDELLAMIELE, E MIELE, L MUKHERJEE, AB TI TISSUE-SPECIFIC EXPRESSION OF THE GENE CODING FOR HUMAN CLARA CELL 10-KD PROTEIN, A PHOSPHOLIPASE-A(2)-INHIBITORY PROTEIN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CLARA CELL 10-KD PROTEIN; UTEROGLOBIN; MESSENGER RNA; GENE EXPRESSION; TISSUE DISTRIBUTION ID UTEROGLOBIN-LIKE PROTEIN; ANTIINFLAMMATORY PEPTIDES ANTIFLAMMINS; PLATELET-ACTIVATING-FACTOR; RABBIT UTEROGLOBIN; HORMONAL-REGULATION; KDA PROTEIN; TRANSGLUTAMINASE; LOCALIZATION; REGION; ANTIGENICITY AB Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s). C1 NICHHD, HUMAN GENET BRANCH,DEV GENET SECT,BLDG 10, ROOM 95242, BETHESDA, MD 20892 USA. NR 53 TC 111 Z9 115 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1993 VL 92 IS 5 BP 2099 EP 2109 DI 10.1172/JCI116810 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MF291 UT WOS:A1993MF29100005 PM 8227325 ER PT J AU STRASSMANN, G FONG, M FRETER, CE WINDSOR, S DALESSANDRO, F NORDAN, RP AF STRASSMANN, G FONG, M FRETER, CE WINDSOR, S DALESSANDRO, F NORDAN, RP TI SURAMIN INTERFERES WITH INTERLEUKIN-6 RECEPTOR-BINDING IN-VITRO AND INHIBITS COLON-26-MEDIATED EXPERIMENTAL CANCER CACHEXIA IN-VIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CANCER CACHEXIA; IL-6; IL-6 RECEPTOR; SURAMIN; COLON-26 TUMOR ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; POTENT INHIBITOR; ANTICANCER DRUG; CROSS-LINKING; WEIGHT-LOSS; CELLS; CHEMOTHERAPY; PURIFICATION; MECHANISMS AB Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20852. GEORGETOWN UNIV,MED CTR,DIV MED ONCOL,WASHINGTON,DC 20007. RP STRASSMANN, G (reprint author), OTSUKA AMER PHARMACEUT INC,DEPT IMMUNOL,9900 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 41 TC 97 Z9 101 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 NOV PY 1993 VL 92 IS 5 BP 2152 EP 2159 DI 10.1172/JCI116816 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MF291 UT WOS:A1993MF29100011 PM 8227330 ER PT J AU TSIGOS, C ARAI, K HUNG, W CHROUSOS, GP AF TSIGOS, C ARAI, K HUNG, W CHROUSOS, GP TI HEREDITARY ISOLATED GLUCOCORTICOID DEFICIENCY IS ASSOCIATED WITH ABNORMALITIES OF THE ADRENOCORTICOTROPIN RECEPTOR GENE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; MUTAGENESIS; FAMILY; IDENTIFICATION; ACHALASIA; MUTATION; CLONING; BINDING AB Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency. The cDNA and gene of the human ACTH receptor were recently cloned. The gene encodes a 297-amino acid protein that belongs to the G protein-coupled superfamily of membrane receptors. We hypothesized that the ACTH receptor gene might be defective in IGD. To examine this, we studied its genomic structure by PCR and direct sequencing in a 5-yr-old proband with the disease, his parents, and grandparents. The proband was a compound heterozygote for two different point mutations, one in each allele: (a) a substitution (C --> T), also found in one allele of the mother and maternal grandmother, which introduced a premature stop codon (TGA) at position 201 of the protein; this mutant receptor lacks its entire carboxy-terminal third and, if expressed, should be unable to transduce the signal; and (b) a substitution (C --> G), also found in one of the paternal alleles, which changed neutral serine120 in the apolar third transmembrane domain of the receptor to a positively charged arginine, probably disrupting the ligand-binding site. Standard ovine corticotropin releasing hormone (oCRH) test in the heterozygote parents and maternal grandmother revealed exaggerated and prolonged ACTH responses, suggestive of subclinical resistance to ACTH. We conclude that IGD in this family appears to be due to defects of the ACTH receptor gene. The oCRH test appears to be useful in ascertaining heterozygosity in this syndrome. C1 GEORGETOWN UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20007. RP TSIGOS, C (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 134 Z9 139 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 NOV PY 1993 VL 92 IS 5 BP 2458 EP 2461 DI 10.1172/JCI116853 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MF291 UT WOS:A1993MF29100048 PM 8227361 ER PT J AU ZIERDT, CH GILL, VJ ZIERDT, WS AF ZIERDT, CH GILL, VJ ZIERDT, WS TI DETECTION OF MICROSPORIDIAN SPORES IN CLINICAL-SAMPLES BY INDIRECT FLUORESCENT-ANTIBODY ASSAY USING WHOLE-CELL ANTISERA TO ENCEPHALITOZOON-CUNICULI AND ENCEPHALITOZOON-HELLEM SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID N-SP; AIDS AB Three polyclonal mouse antisera, to Encephalitozoon cuniculi, Nosema algerae, and Nosema corneum, and two polyclonal rabbit antisera, to E. cuniculi and Encephalitozoon hellem, were used in an indirect fluorescent-antibody assay (IFA) with Enterocytozoon bieneusi, E. cuniculi, and Encephalitgozoon. hellem spores (spores of the last two were taken from culture). Enterocytozoon bieneusi cannot be cultured. By IFA, antisera to E. cuniculi and E. hellem reacted strongly and equally with each other's spores. The mouse antisera reacted strongly with the homologous species, but for these there was segmental and particulate or ''dot'' staining of heterologous microsporidian spores, indicating cross-reactions with more selected antigens. In fecal samples, cross-reactions with both mouse and rabbit antisera were sometimes seen with different yeast species, with species of streptococci, and species of gram-negative rods. There were no cross-reactions to staphylococci. Enterocytozoon bieneusi was easily identified in duodenal and colonic biopsies, duodenal and colonic fluids, and feces of symptomatic AIDS patients by IFA. In a study of 12 AIDS patients with diarrhea, the new IFA identified microsporidia in all of 11 fecal samples, three colon fluids, six duodenal fluids, and three duodenal biopsy touch preparations. Although the fecal sample of 1 of the 12 was negative, the patient's duodenal fluid contained microsporidian spores by IFA. RP ZIERDT, CH (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892, USA. NR 8 TC 52 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1993 VL 31 IS 11 BP 3071 EP 3074 PG 4 WC Microbiology SC Microbiology GA MC289 UT WOS:A1993MC28900048 PM 8263205 ER PT J AU LI, BG GORZIGLIA, M AF LI, BG GORZIGLIA, M TI VP4 SEROTYPE OF THE GOTTFRIED STRAIN OF PORCINE ROTAVIRUS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID MONOCLONAL-ANTIBODIES; PROTEIN AB The antigenic relationships of the VP4 serotype of porcine rotavirus Gottfried strain with other rotaviruses were determined by using antiserum to Gottfried VP4-baculovirus recombinant. This antiserum failed to react significantly with virus of serotypes P1A, P1B, P3, and OSU; however, it reacted with P2 strains. In the reciprocal assay, antiserum to VP4 of an asymptomatic strain (P2) failed to neutralize the Gottfried strain virus to a significant level. It thus appears that the Gottfried strain should be considered a subtype of P2. C1 NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892. NR 11 TC 20 Z9 20 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 NOV PY 1993 VL 31 IS 11 BP 3075 EP 3077 PG 3 WC Microbiology SC Microbiology GA MC289 UT WOS:A1993MC28900049 PM 8263206 ER PT J AU REED, E JANIK, J BOOKMAN, MA ROTHENBERG, M SMITH, J YOUNG, RC OZOLS, RF VANDERMOLEN, L KOHN, E JACOB, JL CORNELISON, TL AF REED, E JANIK, J BOOKMAN, MA ROTHENBERG, M SMITH, J YOUNG, RC OZOLS, RF VANDERMOLEN, L KOHN, E JACOB, JL CORNELISON, TL TI HIGH-DOSE CARBOPLATIN AND RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN ADVANCED-STAGE RECURRENT OVARIAN-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN GM-CSF; AUTOLOGOUS BONE-MARROW; ADVANCED MALIGNANCY; MYELOPOIESIS; PRIMATES; INVIVO; CELLS C1 NCI,FREDERICK CANC RES FACIL,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP REED, E (reprint author), NCI,MED BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 25 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1993 VL 11 IS 11 BP 2118 EP 2126 PG 9 WC Oncology SC Oncology GA ME932 UT WOS:A1993ME93200009 PM 8229126 ER PT J AU GOLDSPIEL, BR KOHLER, DR KOUSTENIS, AG WILSON, WH TOLCHER, AW OSHAUGHNESSY, JA WITTES, RE CHABNER, BA AF GOLDSPIEL, BR KOHLER, DR KOUSTENIS, AG WILSON, WH TOLCHER, AW OSHAUGHNESSY, JA WITTES, RE CHABNER, BA TI PACLITAXEL ADMINISTRATION USING PORTABLE INFUSION PUMPS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TAXOL C1 NCI,BETHESDA,MD 20892. RP GOLDSPIEL, BR (reprint author), WARREN G MAGNUSON CLIN CTR,BETHESDA,MD, USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1993 VL 11 IS 11 BP 2287 EP 2288 PG 2 WC Oncology SC Oncology GA ME932 UT WOS:A1993ME93200035 PM 7901343 ER PT J AU WEINBERGER, DR AF WEINBERGER, DR TI SPECT IMAGING IN PSYCHIATRY - INTRODUCTION AND OVERVIEW SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on SPECT Imaging in Psychiatry: a New Look at Depression, at the 146th Annual Meeting of the American-Psychiatric-Association CY MAY 23, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID EMISSION COMPUTED-TOMOGRAPHY; SINGLE; DEMENTIA; INVIVO AB Positron emission tomography (PET) and single photon emission computed tomography (SPECT) use advanced computer image construction techniques to illustrate regional cerebral function, metabolism, and chemistry. Although the resolution of PET is higher than that of SPECT, and the technical development of SPECT has lagged behind that of PET, SPECT has recently enjoyed increasingly widespread use, particularly because its costs and technology are within the reach of all clinical nuclear medicine facilities. SPECT imaging agents have greater half-lives than those used with PET, thereby permitting longer and more detailed neurochemistry study than is possible with PET. The research value of both methods has unique potential compared with computed tomography (CT) and magnetic resonance imaging (MRI), which traditionally have provided a static image of the brain's structure or anatomy. RP WEINBERGER, DR (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS,WASHINGTON,DC 20032, USA. NR 9 TC 4 Z9 4 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1993 VL 54 SU S BP 3 EP 5 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA MR849 UT WOS:A1993MR84900001 PM 8270596 ER PT J AU GEORGE, MS KETTER, TA POST, RM AF GEORGE, MS KETTER, TA POST, RM TI SPECT AND PET IMAGING IN MOOD DISORDERS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on SPECT Imaging in Psychiatry: a New Look at Depression, at the 146th Annual Meeting of the American-Psychiatric-Association CY MAY 23, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID CEREBRAL BLOOD-FLOW; PHOTON-EMISSION TOMOGRAPHY; MAJOR AFFECTIVE-DISORDERS; HUMAN EXTRASTRIATE CORTEX; DEPRESSED-PATIENTS; GLUCOSE-METABOLISM; COGNITIVE IMPAIRMENT; UNIPOLAR DEPRESSION; SLEEP-DEPRIVATION; VENTRICULAR SIZE AB Single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies are yielding a picture of clinical depression as a disorder associated with dysfunction in specific brain regions. These data support the view of depression as a disease of the brain in general and of the frontal and temporal lobes in particular. Frontal lobe hypometabolism is emerging as a common final pathway for most types of primary and secondary depression, regardless of the original cause. The severity of depression is often related to the degree of frontal hypometabolism, and preliminary studies indicate that the hypometabolism normalizes after treatment in concert with the patient's improved mood. Primary depression also is associated with abnormal activation of key brain areas, including discrete aspects of the frontal and temporal lobes, the amygdala, and the cingulate gyrus. Several areas of research are currently under way using SPECT or PET to explore further the neuroanatomy of depression. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 80 TC 151 Z9 152 U1 12 U2 13 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 NOV PY 1993 VL 54 SU S BP 6 EP 13 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA MR849 UT WOS:A1993MR84900002 PM 8270597 ER PT J AU DENKERS, EY GAZZINELLI, RT MARTIN, D SHER, A AF DENKERS, EY GAZZINELLI, RT MARTIN, D SHER, A TI EMERGENCE OF NK1.1+ CELLS AS EFFECTORS OF IFN-GAMMA DEPENDENT IMMUNITY TO TOXOPLASMA-GONDII IN MHC CLASS-I-DEFICIENT MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; CD8+ T-CELLS; TUMOR-NECROSIS-FACTOR; LYMPHOCYTES-T; BONE-MARROW; SCID MICE; NK CELLS; INFECTION; VIRUS; BETA-2-MICROGLOBULIN AB CD8+ T lymphocytes have been reported to play a major role in the protective immune response against acute infection with Toxoplasma gondii. In order to further assess the role of CD8+ cells in resistance against this protozoan we examined the ability of beta2m-deficient mice, which fail to express MHC class I molecules and peripheral CD8+ lymphocytes, to survive tachyzoite challenge following vaccination with an attenuated parasite mutant. Surprisingly, vaccination of beta2m-deficient mice induced strong resistance to lethal challenge, with >50% surviving beyond 3 months. Vaccinated beta2m-deficient mice, but not control heterozygotes, showed a five- to six-fold expansion in spleen cell number and approximately 40% of the splenocytes were found to express the NK markers NK1.1 and asialo GM1. Spleen cells from the vaccinated beta2m-deficient animals failed to kill either infected host cells or the NK target YAC-1. However, high levels of IFN-gamma were secreted when the cells were cultured in vitro with soluble T gondii lysate, and this response was abolished by NK1.1+ but not CD4+ and CD8+ lymphocyte depletion, implicating the NK1.1+ population as the major source of IFN-gamma. More importantly, vaccine-induced immunity in beta2m-deficient mice was completely abrogated by in vivo administration of antibody to NK1.1, asialo GM1, or IFN-gamma. Together, the data suggest that in class I-deficient mice vaccinated against T gondii, the absence of CD8+ effector cells is compensated for by the emergence of a population of NK1.1+ and asialo GM1+ cells which lack cytolytic activity, and that the protective action of these cells against the parasite is attributable to IFN-gamma production. The induction of this novel NK population may provide an approach for controlling opportunistic infections in immunocompromised hosts. C1 NIAID,ANIM CARE BRANCH,BETHESDA,MD 20892. RP DENKERS, EY (reprint author), NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 41 TC 140 Z9 143 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1993 VL 178 IS 5 BP 1465 EP 1472 DI 10.1084/jem.178.5.1465 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300001 PM 8228800 ER PT J AU PENIX, L WEAVER, WM PANG, Y YOUNG, HA WILSON, CB AF PENIX, L WEAVER, WM PANG, Y YOUNG, HA WILSON, CB TI 2 ESSENTIAL REGULATORY ELEMENTS IN THE HUMAN INTERFERON-GAMMA PROMOTER CONFER ACTIVATION SPECIFIC EXPRESSION IN T-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LIGATION MEDIATED PCR; ANTIGEN RECEPTOR; GENE-EXPRESSION; LYMPHOCYTE-T; TRANSCRIPTION FACTOR; IMMUNE INTERFERON; BINDING PROTEIN; GENOMIC DNA; ENHANCER; LYMPHOKINE AB Like interleukin 2 (IL-2), interferon gamma (IFN-gamma) is an early response gene in T cells and both are prototypical T helper cell type 1 (Th-1) lymphokines. Yet IL-2 and IFN-gamma production are independently regulated, as demonstrated by their differential expression in certain T cell subsets, suggesting that the regulatory elements in these two genes must differ. To explore this possibility, the 5' flank of the human IFN-gamma gene was analyzed. Expression of IFN-gamma promoter-driven beta-galactosidase reporter constructs containing 538 bp of 5' flank was similar to that by constructs driven by the IL-2 promoter in activated Jurkat T cells; expression nearly as great was observed with the construct containing only 108 bp of IFN-gamma 5' flank. These IFN-gamma promoter constructs faithfully mirrored expression of the endogenous gene, in that expression required activation both with ionomycin and PMA, was inhibited by cyclosporin A, and was not observed in U937 or THP-1 cells. The region between -108 and -40 bp in the IFN-gamma promoter was required for promoter function and contained two elements that are conserved across species. Deletion of 10 bp within either element reduced promoter function by 70%, whereas deletions in nonconserved portions of this region had little effect on promoter function. The distal conserved element (-96 to -80 bp) contained a consensus GATA motif and a potential regulatory motif found in the promoter regions of the GM-CSF and macrophage inflammatory protein (MIP) genes. Factors binding to this element, including GATA-3, were found in Jurkat nuclear extracts by electromobility shift assays and two of the three complexes observed were altered in response to activation. One or both of these motifs are present in the 5' flank of multiple, other lymphokine genes, including IL-3, IL-4, IL-5, and GM-CSF, but neither is present in the promoter of the IL-2 gene. The proximal conserved element (-73 to -48 bp) shares homology with the NFIL-2A element in the IL-2 promoter; these elements compete for binding of factors in Jurkat nuclear extracts, although the NFIL-2A element but not the IFN-gamma element binds Oct-1. Factors binding to this element in the IFN-gamma gene were present in extracts from resting and activated Jurkat T cells. However, by in vivo footprinting of intact cells, this element was protected from methylation only with activation. The factors in Jurkat extracts that bound to the proximal and distal conserved elements were not detected in U937 or THP-1 extracts. Notably, the critical regions of the IFN-gamma promoter do not contain sequences homologous to the NF-AT or AP-1 sites in the IL-2 promoter. The differences in essential cis elements in the IFN-gamma and IL-2 promoters, and the factors binding thereto, may play an important role in the differential expression of these genes in naive vs. memory T cells and in the relative preservation of IFN-gamma as compared to IL-2 gene expression in anergic Th-1 T cell clones. C1 UNIV WASHINGTON,DEPT PEDIAT,RD-20,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195. DYN CORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. FU NICHD NIH HHS [HD-06706, HD-18184]; NIGMS NIH HHS [GM-28896] NR 55 TC 176 Z9 180 U1 0 U2 2 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 NOV 1 PY 1993 VL 178 IS 5 BP 1483 EP 1496 DI 10.1084/jem.178.5.1483 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300003 PM 8228802 ER PT J AU MANDLER, R CHU, CC PAUL, WE MAX, EE SNAPPER, CM AF MANDLER, R CHU, CC PAUL, WE MAX, EE SNAPPER, CM TI INTERLEUKIN-5 INDUCES S-MU-S-GAMMA-1 DNA REARRANGEMENT IN B-CELLS ACTIVATED WITH DEXTRAN-ANTI-IGD ANTIBODIES AND INTERLEUKIN-4 - A 3-COMPONENT MODEL FOR IG CLASS SWITCHING SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEAVY-CHAIN SWITCH; GROWTH-FACTOR-BETA; INTERFERON-GAMMA; EPSILON-TRANSCRIPTS; LYMPHOCYTES-B; INDUCTION; LINE; LIPOPOLYSACCHARIDE; IL-5; RECOMBINATION AB The cellular signals required for induction of immunoglobulin (Ig) class switching are only partially understood. Two processes that are considered to be necessary for such induction are DNA synthesis and germline constant heavy (C(H)) gene transcription. We now show that an additional signal, as mediated by interleukin 5 (IL-5), is also required. To induce proliferation of resting B cells, but not Ig secretion, we utilized anti-IgD antibodies conjugated to dextran (alphadelta-dex). The addition of IL-4, a well-established switch factor for the IgG1 subclass, to alphadelta-dex-activated cell cultures failed to induce IgG1 secretion or mIgG1+ cells unless IL-5 was also present. While IL-4 stimulated an increase in germline gamma1 RNA in alphadelta-dex-activated cells, this effect could neither be induced nor enhanced by IL-5. By contrast, IL-5 strongly enhanced steady-state levels of productive gamma1 RNA induced by alphadelta-dex and IL-4, suggesting that IL-5 stimulated IgG1 switch rearrangement. To test this possibility we measured switch (S)mu-Sgamma1 DNA recombination events using a newly developed assay, digestion circularization polymerase chain reaction (DC-PCR). We demonstrated that IL-5 was necessary for induction of Smu-S-gamma1 DNA rearrangement in alphadelta-dex plus IL-4-activated cells but that it had little effect on rearrangement in the absence of IL-4. Our data strongly suggest, therefore, a three-component model for induction of Ig class switching. This model includes germline C(H) gene transcription, DNA synthesis, and a third component that is necessary for recombination. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. FU NIAID NIH HHS [AI32560] NR 46 TC 39 Z9 39 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1993 VL 178 IS 5 BP 1577 EP 1586 DI 10.1084/jem.178.5.1577 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300012 PM 8228808 ER PT J AU SARIN, A ADAMS, DH HENKART, PA AF SARIN, A ADAMS, DH HENKART, PA TI PROTEASE INHIBITORS SELECTIVELY BLOCK T-CELL RECEPTOR-TRIGGERED PROGRAMMED CELL-DEATH IN A MURINE T-CELL HYBRIDOMA AND ACTIVATED PERIPHERAL T-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR NECROSIS FACTOR; DNA FRAGMENTATION; MONOCLONAL-ANTIBODY; INDUCED APOPTOSIS; SERINE PROTEASE; PLASMA-MEMBRANE; IL-2 PRODUCTION; LEUKEMIA-CELLS; CYTO-TOXICITY; CYCLE BLOCK AB The hypothesis that cytoplasmic proteases play a functional role in programmed cell death was tested by examining the effect of protease inhibitors on the T cell receptor-mediated death of the 2B4 murine T cell hybridoma and activated T cells. The cysteine protease inhibitors trans-epoxysuccininyl-L-leucylamido-(4-guanidino) butane (E-64) and leupeptin, the calpain selective inhibitor acetyl-leucyl-leucyl-normethional, and the serine protease inhibitors diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, all showed dose-dependent blocking of the 2B4 death response triggered by the T cell receptor complex and by anti-Thy-1. These protease inhibitors enhanced rather than inhibited IL-2 secretion triggered by T cell receptor cross-linking, showing that they did not act by preventing signal transduction. Growth inhibition induced by cross-linking the 2B4 T cell receptor, measured by inhibition of thymidine incorporation, was not generally blocked by these protease inhibitors. All five of these protease inhibitors enhanced rather than blocked 2B4 cell death triggered by dexamethasone, an agent previously shown to have a death pathway antagonistic with that of the TCR. 2B4 cytolysis by the cytotoxic agents staphylococcal alpha-toxin and dodecyl imidazole, and that caused by hypotonic conditions, was not significantly affected by the five protease inhibitors tested. The selected protease inhibitors blocked both the apoptotic nuclear morphology changes and DNA fragmentation induced by T cell receptor cross-linking, and enhanced both these properties induced by dexamethasone in 2B4 cells. The T cell receptor-induced death of activated murine lymph node T cells and human peripheral blood CD4+ T cells was blocked by both cysteine and serine protease inhibitors, showing that the protease-dependent death pathway also operates in these systems. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. RI Adams, David/C-9092-2009 NR 53 TC 210 Z9 211 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1993 VL 178 IS 5 BP 1693 EP 1700 DI 10.1084/jem.178.5.1693 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300024 PM 8228816 ER PT J AU WIEST, DL YUAN, L JEFFERSON, J BENVENISTE, P TSOKOS, M KLAUSNER, RD GLIMCHER, LH SAMELSON, LE SINGER, A AF WIEST, DL YUAN, L JEFFERSON, J BENVENISTE, P TSOKOS, M KLAUSNER, RD GLIMCHER, LH SAMELSON, LE SINGER, A TI REGULATION OF T-CELL RECEPTOR EXPRESSION IN IMMATURE CD4+CD8+ THYMOCYTES BY P56(LCK) TYROSINE KINASE - BASIS FOR DIFFERENTIAL SIGNALING BY CD4 AND CD8 IN IMMATURE THYMOCYTES EXPRESSING BOTH CORECEPTOR MOLECULES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; PROTEIN-KINASE; MONOCLONAL-ANTIBODIES; POSITIVE SELECTION; TRANSGENIC MICE; ZETA-CHAIN; P56LCK; PHOSPHORYLATION; ASSOCIATION; SURFACE AB Signals transduced through the T cell antigen receptor (TCR) are modulated by the src family tyrosine kinase p56lck (lck), which associates in mature T cells with the coreceptor molecules CD4 and CD8. Here we describe a novel function of lck in immature CD4+CD8+ thymocytes, that of regulating TCR expression. Activation of lck in immature CD4+CD8+ thymocytes by intrathymic engagement of CD4 maintains low TCR expression by causing most TCR components to be retained and degraded within the endoplasmic reticulum. Importantly, activation of lck in immature CD4+CD8+ thymocytes results from engagement of surface CD4 molecules, but not surface CD8 molecules, despite the nearly fourfold greater surface expression of CD8 than CD4. The competence of CD4 to activate lck in CD4+CD8+ thymocytes relates to the fact that a relatively large fraction of surface CD4 molecules (25-50%) are associated with intracellular lck molecules, whereas only 2% of surface CD8 molecules are associated with lck. The amount of lck associated with CD4 in CD4+CD8+ thymocytes is diminished by chronic CD4 engagement in the thymus, as activated lck molecules subsequently dissociate from CD4. Indeed, the amount of lck associated with CD4 in CD4+CD8+ thymocytes is markedly increased in major histocompatibility complex (MHC) class II- mice that lack the intrathymic ligand for CD4 and in which surface CD4 molecules are consequently not engaged. Thus, the present study demonstrates that (a) activation of lck in CD4+CD8+ thymocytes regulates distribution and expression of TCR components; (b) unlike CD4 molecules, CD8 molecules on CD4+CD8+ thymocytes cannot efficiently activate lck despite their significantly greater surface expression; and (c) the amount of lck associated with CD4 in the CD4+CD8+ thymocytes is inversely related to the extent of CD4 engagement by MHC class II molecules in the thymus. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL & MED,BOSTON,MA 02115. RP WIEST, DL (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. OI Wiest, David/0000-0002-0792-3188 NR 48 TC 134 Z9 134 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 NOV 1 PY 1993 VL 178 IS 5 BP 1701 EP 1712 DI 10.1084/jem.178.5.1701 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300025 PM 8228817 ER PT J AU PALIOGIANNI, F KINCAID, RL BOUMPAS, DT AF PALIOGIANNI, F KINCAID, RL BOUMPAS, DT TI PROSTAGLANDIN-E(2) AND OTHER CYCLIC-AMP ELEVATING AGENTS INHIBIT INTERLEUKIN-2 GENE-TRANSCRIPTION BY COUNTERACTING CALCINEURIN-DEPENDENT PATHWAYS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID PROTEIN PHOSPHATASE; LYMPHOCYTES-T; EXPRESSION; CELL; CAMP; ACTIVATION; SUPPRESSION; CALMODULIN; PROMOTER; RELEASE AB We have previously shown that prostaglandin E2 and other cAMP elevating agents inhibit the nuclear transcription of the human IL-2 gene by interfering with a Ca2+-sensitive T cell signal transduction pathway. Calcineurin, a Ca2+/calmodulin-dependent 2B protein phosphatase, is an essential component of the T cell receptor signal transduction pathway leading to IL-2 gene expression. We have therefore tested the hypothesis that this phosphatase may be a target for the inhibitory effects of cAMP on IL-2 gene transcription. We report here that PGE2 markedly reduces the IL-2 promoter activity that is induced by a constitutively active form of calcineurin. In contrast to the complete inhibition of promoter activity produced by the immunosuppressants cyclosporin A and FK-506, this partial block suggests that PGE2 modulates downstream events needed for lymphokine gene activation. Overexpression of calcineurin in Jurkat cells decreases their apparent sensitivity to the inhibitory effects of PGE2 consistent with the fact that this enzyme plays a physiological role in dephosphorylating substrates of cAMP-dependent kinases in several tissues. These results provide evidence that cAMP-dependent pathways may antagonize calcineurin-regulated cascades for T cell activation in vivo, and suggest crosstalk between the Ca2+ and the cAMP signaling pathways during T cell activation. C1 NIAAA,IMMUNOL SECT,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892. RP PALIOGIANNI, F (reprint author), NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BLDG 10,ROOM 3N112,BETHESDA,MD 20892, USA. NR 27 TC 86 Z9 87 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 NOV 1 PY 1993 VL 178 IS 5 BP 1813 EP 1817 DI 10.1084/jem.178.5.1813 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MD953 UT WOS:A1993MD95300039 PM 7693857 ER PT J AU HEMMEN, F PARAF, A SMITHGILL, S AF HEMMEN, F PARAF, A SMITHGILL, S TI LYSOZYMES IN EGGS AND PLASMA FROM CHICKEN, DUCK AND GOOSE - CHOICE AND USE OF MABS TO DETECT ADULTERANTS IN FOIE-GRAS SO JOURNAL OF FOOD SCIENCE LA English DT Article DE CHICKEN; DUCK; GOOSE; LIVER; LYSOZYMES; ADULTERATION; FOIE-GRAS ID HEATED MEAT-PRODUCTS; MONOCLONAL-ANTIBODIES; WHITE LYSOZYME; ENZYME IMMUNOASSAYS; SOYA PROTEIN; EXPRESSION; IDENTIFICATION; SPECIFICITY; OVALBUMIN; ANTIGENS AB Lysozymes from either egg-white or plasma were found to be different by monoclonal antibodies (mAbs). For improving texture of ''foie gras'' or for economical reasons, adulterants such as fresh livers from chicken or turkey or hen egg-white have been used. Duck or goose ''foie gras'' were not detected by anti-duck lysozyme mAbs, while positive reactions were obtained with anti-hen-egg-white lysozyme (HEWL). Similarly, anti-HEWL mAbs detected chicken or turkey fresh liver in duck or goose ''foie gras'' even after heating at 80-degrees-C. In 110-degrees-C heated ''foie gras'' only mAbs HyHEL (hybridoma anti-hen-egg-white lysozyme) 5 and HyHEL 10 were effective to detect fresh hen livers. C1 INRA,PATHOL & IMMUNOL LAB,F-37380 NOUZILLY,FRANCE. NCI,GENET LAB,FREDERICK,MD 21701. NR 28 TC 12 Z9 12 U1 0 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD NOV-DEC PY 1993 VL 58 IS 6 BP 1291 EP 1293 DI 10.1111/j.1365-2621.1993.tb06168.x PG 3 WC Food Science & Technology SC Food Science & Technology GA MM967 UT WOS:A1993MM96700023 ER PT J AU CROUCH, DJ BIRKY, MM GUST, SW ROLLINS, DE WALSH, JM MOULDEN, JV QUINLAN, KE BECKEL, RW AF CROUCH, DJ BIRKY, MM GUST, SW ROLLINS, DE WALSH, JM MOULDEN, JV QUINLAN, KE BECKEL, RW TI THE PREVALENCE OF DRUGS AND ALCOHOL IN FATALLY INJURED TRUCK DRIVERS SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE TOXICOLOGY; ETHANOL; COCAINE; THC; THC-COOH; CAFFEINE; IMPAIRMENT; FATAL-TO-THE-DRIVER TRUCKING CRASHES; ACCIDENTAL DEATH ID PILOT PERFORMANCE; MARIJUANA; COCAINE; PLASMA AB To assess the impact of alcohol and other drug use in the trucking industry, the National Transportation Safety Board, in collaboration with The National Institute on Drug Abuse investigated fatal-to-the-driver trucking accidents in eight states over a one year period. Comprehensive drug screens were performed on blood specimens collected from 168 fatally injured drivers. One or more drugs were detected in 67% of the drivers and 33% of the drivers had detectable blood concentrations of psychoactive drugs or alcohol. The most prevalent drugs were cannabinoids and ethanol, each found in 13% of the drivers. Cocaine or benzoylecgonine was found in 8% of the cases. Seven percent of the driver's blood specimens contained amphetamine or methamphetamine and 7% contained phenylpropanolamine, ephedrine, or pseudoephedrine. A panel of toxicologists reviewed the accident investigation report and the toxicology findings for each case and determined that impairment due to marijuana use was a factor in all cases where the delta-9-tetrahydrocannabinol concentration exceeded 1.0 ng/mL and that alcohol impairment contributed to all accidents where the blood alcohol concentration was 0.04% wt/vol or greater. In 50 of 56 cases where psychoactive drugs or alcohol were found, impairment due to substance use contributed to the fatal accident. C1 NATL TRANSPORTAT SAFETY BOARD,ALCOHOL PROGRAM,WASHINGTON,DC. NIDA,ROCKVILLE,MD. PRESIDENTS DRUG ADVISORY COUNCIL,WASHINGTON,DC. TRANSPORTAT SAFETY ASSOCIATES,TAKOMA PK,MD. UNIV ARKANSAS,COLL MED,LITTLE ROCK,AR 72205. RP CROUCH, DJ (reprint author), UNIV UTAH,CTR HUMAN TOXICOL,417 WAKARA WAY,SUITE 290,SALT LAKE CITY,UT 84108, USA. NR 38 TC 57 Z9 59 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1993 VL 38 IS 6 BP 1342 EP 1353 PG 12 WC Medicine, Legal SC Legal Medicine GA MH369 UT WOS:A1993MH36900016 PM 8263478 ER PT J AU BERENCSI, K RANDO, RF DETAISNE, C PAOLETTI, E PLOTKIN, SA GONCZOL, E AF BERENCSI, K RANDO, RF DETAISNE, C PAOLETTI, E PLOTKIN, SA GONCZOL, E TI MURINE CYTOTOXIC T-CELL RESPONSE SPECIFIC FOR HUMAN CYTOMEGALOVIRUS GLYCOPROTEIN-B (GB) INDUCED BY ADENOVIRUS AND VACCINIA VIRUS RECOMBINANTS EXPRESSING GB SO JOURNAL OF GENERAL VIROLOGY LA English DT Note ID TOXIC LYMPHOCYTES-T; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; ENVELOPE GLYCOPROTEIN; INFECTED CELLS; GP55-116 GB; INDUCTION; PROTEIN; COMPLEX; EPITOPE AB A murine model of the cytotoxic T lymphocyte (CTL) response to glycoprotein B (gB) of human cytomegalovirus (HCMV) was developed based on the use of adenovirus (Ad) and vaccinia virus (Vac) recombinants expressing gB. Mice of different major histocompatibility haplotypes [CBA (H-2k), BALB/k (H-2k) and BALB/c (H-2d)] infected with the Ad-gB recombinant developed an Ad-specific CTL response. However, only the H-2k mice developed a significant HCMV gB-specific CTL response, as indicated by the major histocompatibility complex class I-restricted lysis of Vac strain Copenhagen (VacC)-gB recombinant-infected target cells by H-2k mouse immune spleen cells. The VacC-gB recombinant elicited only a weak gB-specific CTL response in these mice, indicating that the observed gB-specific CTL response in mice is dependent on the expression vector used for immunization. The gB-specific cytotoxicity observed in H-2k mice was mediated by the CD8 lymphocyte subset. C1 NIDR,BETHESDA,MD 20892. INST PASTEUR,69280 MARCY LETOILE,FRANCE. VIROGENET CORP,TROY,NY 12180. RP BERENCSI, K (reprint author), WISTAR INST ANAT & BIOL,3601 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NICHD NIH HHS [HD18957] NR 27 TC 26 Z9 26 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1993 VL 74 BP 2507 EP 2512 DI 10.1099/0022-1317-74-11-2507 PN 11 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA MF244 UT WOS:A1993MF24400027 PM 8245869 ER PT J AU HOELZEL, AR HALLEY, J OBRIEN, SJ CAMPAGNA, C ARNBOM, T LEBOEUF, B RALLS, K DOVER, GA AF HOELZEL, AR HALLEY, J OBRIEN, SJ CAMPAGNA, C ARNBOM, T LEBOEUF, B RALLS, K DOVER, GA TI ELEPHANT SEAL GENETIC-VARIATION AND THE USE OF SIMULATION-MODELS TO INVESTIGATE HISTORICAL POPULATION BOTTLENECKS SO JOURNAL OF HEREDITY LA English DT Article ID MITOCHONDRIAL-DNA AB Because the northern elephant seal (Mirounga angustirostrus) was heavily exploited during the 19th century, it experienced an extreme population bottleneck. Since then, under legislative protection in the United States and Mexico, northern elephant seals have recovered dramatically in number, although their genomic diversity was greatly reduced, apparently as a consequence of the bottleneck. In this study we investigated DNA sequence diversity in two mtDNA regions (the control region and 16S RNA) and found low genetic variation in the northern elephant seal: there were only two control region haplotypes (sequence difference = 1%), which was consistent with an extreme founder event in the recent history of the northern species. We also reaffirmed the lack of allozyme diversity in this species. In contrast, the Southern elephant seal (M. leonina), which though similarly exploited never fell below 1,000 animals, had 23 control region mtDNA haplotypes (average sequence difference = 2.3%). To investigate the extent of the founder event in the northern elephant seal we devised a simulation model based on extensive demographic data. This allowed a statistical analysis of the likely outcome of bottlenecks of different size and duration. Given these historical data, our results indicate (within 95% confidence) a bottleneck of less than 30 seals and 20-year duration, or, if hunting was the primary pressure on the population, a single-year bottleneck of less than 20 seals. C1 IMPERIAL COLL,NERC,CTR POPULAT BIOL,ASCOT,BERKS,ENGLAND. DEPT GENET,CAMBRIDGE,CAMBS,ENGLAND. CTR NACL PATAGON,PUERTO MADRYN,CHUBUT,ARGENTINA. BRITISH ANTARCTIC SURVEY,CAMBRIDGE,ENGLAND. STOCKHOLM UNIV,DEPT ZOOL,STOCKHOLM,SWEDEN. UNIV CALIF SANTA CRUZ,DEPT BIOL,SANTA CRUZ,CA 95064. UNIV CALIF SANTA CRUZ,INST MARINE SCI,SANTA CRUZ,CA 95064. SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008. RP HOELZEL, AR (reprint author), NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. OI Campagna, Claudio/0000-0002-7971-5062 NR 29 TC 158 Z9 167 U1 5 U2 46 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD NOV-DEC PY 1993 VL 84 IS 6 BP 443 EP 449 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA MM565 UT WOS:A1993MM56500004 PM 7505788 ER PT J AU MARTINEZ, A BURRELL, MA KUIJK, M MONTUENGA, LM TRESTON, A CUTTITTA, F POLAK, JM AF MARTINEZ, A BURRELL, MA KUIJK, M MONTUENGA, LM TRESTON, A CUTTITTA, F POLAK, JM TI LOCALIZATION OF AMIDATING ENZYMES (PAM) IN RAT GASTROINTESTINAL-TRACT SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE AMIDATION; PAM; PHM; PAL; RAT GASTROINTESTINAL TRACT; GASTRIN; GLUCAGON; GLP1; IMMUNOCYTOCHEMISTRY; IN-SITU HYBRIDIZATION ID INTESTINAL-PEPTIDE; MONOOXYGENASE PAM; ALPHA-AMIDATION; ENDOCRINE-CELLS; MESSENGER-RNAS; EXPRESSION; GASTRIN; PITUITARY; FORMS; SOMATOSTATIN AB We studied the distribution of the two enzymes involved in post-translational C-terminal alpha-amidation of regulatory peptides in rat digestive tract, using immunocytochemical methods and in situ hybridization techniques. The enzymes were located in most of the fibers and neurons of the myenteric and submucous plexus throughout the entire digestive tract and in endocrine cells of the stomach and colon. Staining of reverse-face serial sections demonstrated that the enzymes in endocrine cells of the stomach co-localized with gastrin in the bottom of the gastric glands. Some gastrin-immunoreactive cells near the neck of the gland were negative for PAM, suggesting that amidation takes place only in the more mature cells. In the colon all cells immunoreactive for glucagon and GLP1 were also positive for peptidylglycine alpha-hydroxylating monooxygenase (PHM) but not for peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). The absence of immunoreactivity for the amidating enzymes in endocrine cells of the small intestine, known to produce C-terminally amidated peptides, suggests the existence of other amidating enzymes. C1 NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, BETHESDA, MD 20892 USA. ROYAL POSTGRAD MED SCH, DEPT HISTOCHEM, LONDON W12 0HS, ENGLAND. RP MARTINEZ, A (reprint author), UNIV NAVARRA, DEPT CYTOL & HISTOL, E-31080 PAMPLONA, SPAIN. RI Martinez, Alfredo/A-3077-2013; Burrell, Maria/J-2570-2012 OI Martinez, Alfredo/0000-0003-4882-4044; Burrell, Maria/0000-0002-8018-764X NR 36 TC 23 Z9 23 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD NOV PY 1993 VL 41 IS 11 BP 1617 EP 1622 PG 6 WC Cell Biology SC Cell Biology GA MD734 UT WOS:A1993MD73400005 PM 8409369 ER PT J AU JACOBSEN, SEW RUSCETTI, FW ROBERTS, AB KELLER, JR AF JACOBSEN, SEW RUSCETTI, FW ROBERTS, AB KELLER, JR TI TGF-BETA IS A BIDIRECTIONAL MODULATOR OF CYTOKINE RECEPTOR EXPRESSION ON MURINE BONE-MARROW CELLS - DIFFERENTIAL-EFFECTS OF TGF-BETA-1 AND TGF-BETA-3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; SIGNAL TRANSDUCTION; PROPOSED MECHANISM; PROLIFERATION; INHIBITION; FACTOR-BETA-1; CULTURES; LINES AB Transforming growth factor beta (TGF-beta), an immunomodulator, has inhibitory as well as stimulatory effects on bone marrow cells. In this study, we demonstrate that TGF-beta1 also is a bidirectional modulator of CSF receptor expression on murine bone marrow cells. TGF-beta1 up-regulated granulocyte-macrophage (GM)-CSF receptor expression in a time- and dose-dependent manner, with a maximum up-regulation of 64% by 48 h at 20 ng/ml. In contrast, TGF-beta1 down-modulated IL-3 and CSF-1 receptor expression by 54 and 55%, respectively, by 24 h. TGF-beta1 did not affect G-CSF receptor expression, in agreement with its inability to affect G-CSF-induced proliferation. The CSF receptor modulation induced by TGF-beta1 preceded its effects on CSF-stimulated proliferation. The effects of TGF-beta on CSF receptor expression were isoform dependent, thus TGF-beta3 was a 10-fold more potent inhibitor of both IL-3-induced colony formation and IL-3 receptor expression than TGF-beta1, whereas TGF-beta1 was a more potent stimulator of GM-CSF-stimulated colonies and GM-CSF receptor expression than TGF-beta3. Therefore, the ability of TGF-beta to modulate the CSF receptor density/cell and/or the actual number of progenitors expressing CSF receptors directly correlates with the multifunctional effects of TGF-beta in hematopoiesis. C1 NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NCI, LEUKOCYTE BIOL LAB, BIOL RESPONSE MODIFIERS PROGRAM, BETHESDA, MD 20892 USA. NCI, BIOL CARCINOGENESIS & DEV PROGRAM, BETHESDA, MD 20892 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CO-74102] NR 58 TC 46 Z9 47 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1993 VL 151 IS 9 BP 4534 EP 4544 PG 11 WC Immunology SC Immunology GA MD349 UT WOS:A1993MD34900013 PM 8409417 ER PT J AU MCCOY, KL GAINEY, D INMAN, JK STUTZMAN, R AF MCCOY, KL GAINEY, D INMAN, JK STUTZMAN, R TI ANTIGEN PRESENTATION BY B-LYMPHOMA CELLS - REQUIREMENTS FOR PROCESSING OF EXOGENOUS ANTIGEN INTERNALIZED THROUGH TRANSFERRIN RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; PROTEIN-SYNTHESIS; LYMPHOCYTES-B; MEDIATED ENDOCYTOSIS; MOLECULES; ENDOSOMES; COMPLEXES; LYSOSOMES; COMPARTMENT; KINETICS AB The Ag, pigeon cytochrome c, was delivered to the early endosomes in a form coupled to human ferric transferrin that entered APC through transferrin receptors. The processing of the transferrin-Ag conjugate by B lymphoma cells was compared with that of unconjugated native Ag that entered APC by a nonreceptor-mediated mechanism. Within 5 min after internalization, catabolized conjugate was detected in isolated early endosomes and did not accumulate in these organelles. Analysis of the rapid catabolism of the conjugate demonstrated that the Ag, not the transferrin, portion of the molecule was degraded by the APC, suggesting that similar proteases may mediate the processing of the conjugate and native Ag. The processing mechanisms of these molecules shared similarities. Treatment of APC with chloroquine or paraformaldehyde interfered with the stimulation of Ag-specific CD4+ T cells by both transferrin-Ag conjugate and native Ag. However, the T cell responses to the conjugate and native Ag were different in two important respects. First, T cell activation by the conjugate began at an earlier time point and occurred at a faster rate than T cell stimulation by the same concentration of native Ag during a 3-h time course. Second, the T cell response to the conjugate, but not to native Ag, was diminished by treating APC with cycloheximide, a reversible protein synthesis inhibitor. This partial inhibition of the conjugate response by cycloheximide could not be attributed to significant effects on transferrin receptor expression, or on internalization, recycling, or degradation of the conjugate. The differential cycloheximide-sensitivity of the T cell responses indicates that the processing pathways of the two molecules are different. Our findings suggest that the early endosomes may function as an Ag-processing compartment, and that more than one pathway may lead to productive processing in B lymphoma cells. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP MCCOY, KL (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL & IMMUNOL,BOX 678,MCV STN,RICHMOND,VA 23298, USA. FU NIAID NIH HHS [AI28422] NR 41 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1993 VL 151 IS 9 BP 4583 EP 4594 PG 12 WC Immunology SC Immunology GA MD349 UT WOS:A1993MD34900018 PM 8409420 ER PT J AU GARZA, HH MAYO, S BOWEN, WD DECOSTA, BR CARR, DJJ AF GARZA, HH MAYO, S BOWEN, WD DECOSTA, BR CARR, DJJ TI CHARACTERIZATION OF A (+)-AZIDOPHENAZOCINE-SENSITIVE SIGMA-RECEPTOR ON SPLENIC LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GUINEA-PIG BRAIN; H-3 (+)-PENTAZOCINE; BINDING-SITES; RAT; IDENTIFICATION; LIGANDS; DRUGS; CELLS AB A study was undertaken to structurally define and functionally assess sigma receptors on splenocytes using the highly selective sigma ligand (+)-azidophenazocine. Radioreceptor assays under reduced lighting show (+)-azidophenazocine can effectively block the binding of sigma ligands [H-3]haloperidol (IC50 = 30 nM, K(i) = 19.0 nM) and [H-3](+)-pentazocine (IC50 = 40 nM, K(i) = 350 nM), but not the dopamine (D2) ligand [H-3]spiperone (IC50 > 5 muM) to splenic lymphocytes. [H-3](+)-1-Propyl-3-(3-hydroxyphenyl)piperidine ([H-3](+)-PPP) sites (K(d) = 40.8 nM, B(max) = 2.32 pmol/mg) were also present on these lymphocytes. Additional studies using [H-3](+)-azidophenazocine indicated the presence of saturable sites (K(d) = 29.7 nM, B(max) = 760 fmol/mg) on splenic lymphocytes. There are no significant differences in affinity between sites found on T-enriched (K(d) = 59 +/- 47 nM) and B-enriched lymphocytes (K(d) = 23 +/- 5 nM). Photoaffinity labeling studies of splenocyte membranes with [H-3](+)-azidophenazocine revealed a protein migrating at an apparent m.w. of 57 kDa under reducing and nonreducing conditions on SDS-PAGE. The labeling was specific because pretreatment with unlabeled haloperidol, (+)-PPP, 1,3 di(2-tolyl) guanidine, (+)-pentazocine, and (+)-azidophenazocine before cross-linking competed away > 75% of the radioactivity associated with the protein, whereas (-)-pentazocine and naloxone were significantly less effective. This data together with the observation that both (+)-azidophenazocine or haloperidol inhibit Con A-induced production of IFN by splenocytes, indicates that lymphocytes possess a biologically relevant sigma receptor. C1 LOUISIANA STATE UNIV,MED CTR,DEPT MICROBIOL IMMUNOL & PARASITOL,1901 PERDIDO ST,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,CTR ALCOHOL & DRUG ABUSE,BATON ROUGE,LA 70803. LOUISIANA STATE UNIV,MED CTR,CTR NEUROSCI,NEW ORLEANS,LA 70112. NIDDKD,MEDICINAL CHEM LAB,BETHESDA,MD 20892. NR 21 TC 22 Z9 23 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1993 VL 151 IS 9 BP 4672 EP 4680 PG 9 WC Immunology SC Immunology GA MD349 UT WOS:A1993MD34900027 PM 7691955 ER PT J AU ROTTEM, M GOFF, JP ALBERT, JP METCALFE, DD AF ROTTEM, M GOFF, JP ALBERT, JP METCALFE, DD TI THE EFFECTS OF STEM-CELL FACTOR ON THE ULTRASTRUCTURE OF FC-EPSILON-RI+ CELLS DEVELOPING IN IL-3-DEPENDENT MURINE BONE-MARROW-DERIVED CELL-CULTURES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CONNECTIVE-TISSUE-TYPE; COLONY-STIMULATING FACTOR; GROWTH-FACTOR ACTIVITY; MOUSE MAST-CELLS; C-KIT RECEPTOR; HUMAN BASOPHILS; KINASE RECEPTOR; SI-LOCUS; T-CELLS; P-CELL AB Stem cell factor (SCF) is known to alter the proteoglycans, proteases, and cytokines synthesized by mast cells and to activate basophils. To determine whether SCF could also effect the ultrastructural characteristics of basophils and mast cells, we examined the ultrastructure of these FcepsilonRI+ cells over 42 days in IL-3-dependent murine bone marrow-derived cell cultures in the presence or absence of SCF. Initial experiments revealed that the addition of SCF to IL-3-dependent cells enhanced their proliferative rate without influencing the percentage of FcepsilonRI+ or metachromatic cells. We next isolated the FcepsilonRI+ cells using flow cytometry. Light microscopy of these cells revealed mixed cultures of both immature and mature mast cells and basophils with mature mast cells predominating by 3 wk. One hundred to 150 FcepsilonRI+ cells were then photographed by electron microscopy at 3, 10, 21, and in some cases, 42 days of culture, and the ultrastructure of each cell was evaluated by morphometry. Each cell was scored as a mast cell or basophil using standard criteria. Analysis of this data revealed that SCF in the presence of IL-3 promoted the development of mast cells, although a significant number of basophils were noted at day 21 but were absent by day 42. When bone marrow cells cultured in IL-3 + SCF were compared with cells cultured in IL-3 alone, a significant decrease in cell and nuclear size and granule number and size was noted in both mast cells and basophils cultured in IL-3 + SCF, and basophils and mast cells under these conditions most resemble their in vivo counterparts. Thus, SCF in the presence of IL-3 increases the ratio of mast cells to basophils and alters the ultrastructural characteristics of mast cells and basophils toward a more mature phenotype. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20952. RP ROTTEM, M (reprint author), NIAID,MAST CELL PHYSIOL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C-210,BETHESDA,MD 20892, USA. NR 64 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1993 VL 151 IS 9 BP 4950 EP 4963 PG 14 WC Immunology SC Immunology GA MD349 UT WOS:A1993MD34900055 PM 7691960 ER PT J AU KAWAKAMI, Y HAAS, GP LOTZE, MT AF KAWAKAMI, Y HAAS, GP LOTZE, MT TI EXPANSION OF TUMOR-INFILTRATING LYMPHOCYTES FROM HUMAN TUMORS USING THE T-CELL GROWTH-FACTORS INTERLEUKIN-2 AND INTERLEUKIN-4 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN 2; INTERLEUKIN 4; TUMOR-INFILTRATING LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY ID ACTIVATED KILLER CELLS; HUMAN METASTATIC MELANOMAS; RECOMBINANT INTERLEUKIN-2; CLONAL ANALYSIS; ANTITUMOR-ACTIVITY; AUTOLOGOUS TUMOR; PERIPHERAL-BLOOD; CYTO-TOXICITY; FUNCTIONAL-CHARACTERIZATION; LYMPHOID-CELLS AB We examined the role of two T cell-growth factors, interleukin (IL)-2 and IL-4, in expansion of tumor-infiltrating lymphocytes (TILs) from human tumors. In sarcoma, IL-4 (1,000 U/ml) with IL-2 (10 or 1,000 U/ml) grew TILs better than did IL-2 alone in six of 10 cases during 6 weeks of culture. IL-4 decreased the relative number of CD56+ cells, which correlated with a decrease in cytolysis against Daudi in six of 10 cases. The addition of IL-4 with 1,000 U of IL-2 maintained or increased cytolysis against autologous sarcoma, while decreasing nonspecific cytolysis against Daudi or allogeneic sarcoma in three of eight cases. IL-4 decreased cytolysis against both autologous sarcoma and Daudi in four of 10 cases, suggesting nonspecific activity in these instances. In renal cell cancer (RCC), IL-4 with IL-2 (10 or 1,000 U/ml) augmented TIL growth in six of eight cases, especially during the first 2-3 weeks of culture. IL-4 with 10 U of IL-2 increased cytolysis against both autologous RCC and Daudi in six of eight cases, suggesting possible prior cell activation. In contrast, IL-4 addition with 1,000 U of IL-2 maintained or increased cytolysis against autologous RCC, while decreasing cytolysis against Daudi or allogeneic RCC in four of eight cases. In cases of bladder and of prostate cancer, IL-4 with 1,000 U of IL-2 grew TILs slightly better in five of seven cases for the first 2-3 weeks. Bladder TILs grown with IL-2 and/or IL-4 were CD+ T cell predominant (three of five) and rarely lytic for autologous tumor. In colon cancer and hepatoma, TILs grown with IL-2 and/or IL-4 were nonlytic for the autologous tumor. IL-4 in conjunction with IL-2 could therefore augment growth of some TILs especially for the first 2-3 weeks from various human tumors. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 52 TC 10 Z9 11 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1993 VL 14 IS 4 BP 336 EP 347 DI 10.1097/00002371-199311000-00014 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA MD940 UT WOS:A1993MD94000014 PM 8280717 ER PT J AU RABKIN, CS HATZAKIS, A GRIFFITHS, PD PILLAY, D RAGNI, MV HILGARTNER, MW GOEDERT, JJ AF RABKIN, CS HATZAKIS, A GRIFFITHS, PD PILLAY, D RAGNI, MV HILGARTNER, MW GOEDERT, JJ TI CYTOMEGALOVIRUS-INFECTION AND RISK OF AIDS IN HUMAN-IMMUNODEFICIENCY-VIRUS - INFECTED HEMOPHILIA PATIENTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID PROGRESSION; DISEASE; ANTIBODY; TYPE-1 AB The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV ATHENS,SCH MED,CTR NATL RETROVIRUS REF,ATHENS,GREECE. ROYAL FREE HOSP,SCH MED,DIV COMMUNICABLE DIS,LONDON,ENGLAND. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. HEMOPHILIA CTR WESTERN PENN,PITTSBURGH,PA. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. FU NCI NIH HHS [CO-74102, CP-85649, CP-95663] NR 16 TC 47 Z9 48 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 NOV PY 1993 VL 168 IS 5 BP 1260 EP 1263 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MC890 UT WOS:A1993MC89000027 PM 7710460 ER PT J AU GAUDET, SJ SLOMINSKI, A ETMINAN, M PRUSKI, D PAUS, R NAMBOODIRI, MAA AF GAUDET, SJ SLOMINSKI, A ETMINAN, M PRUSKI, D PAUS, R NAMBOODIRI, MAA TI IDENTIFICATION AND CHARACTERIZATION OF 2 ISOZYMIC FORMS OF ARYLAMINE N-ACETYLTRANSFERASE IN SYRIAN-HAMSTER SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE N-ACETYLSEROTONIN; N-ACETYLDOPAMINE; DETOXIFICATION; MELATONIN ID ACETYLATION POLYMORPHISM; MELATONIN SYNTHESIS; INBRED HAMSTER; PINEAL; STIMULATION; EXPRESSION; SEROTONIN AB Arylamine N-acetyltransferase (EC 2.3.1.5) activity was examined using skin from Syrian hamster. Two isozymes of arylamine N-acetyltransferase, designated NAT-1 and NAT-2, were detected on anion-exchange high-performance liquid chromatography analysis. Both enzyme activities had indistinguishable molecular masses (30 kDa), but differed significantly in their specificity toward the aromatic amines including serotonin, dopamine, methoxytryptamine, tryptamine, para-phenetidine, para-aminobenzoic acid, and sulphamethazine. Specifically, NAT-2 but not NAT-1 catalyzed acetylation of dopamine to N-acetyldopamine and acetylation of serotonin to form N-acetylserotonin, a direct precursor of melatonin. The two isozymes were also distinguishable based upon their sensitivity toward methotrexate inhibition (50% inhibiting dose for NAT-1 = 380 muM; NAT-2 > 2 mM). The presence of these two activities in the skin raises new questions about the physiologic role of this enzyme in general and in the skin-specific functions in particular. C1 ALBANY MED COLL,DEPT MICROBIOL IMMUNOL & MOLEC GENET,ALBANY,NY 12208. UKRV,FREE UNIV BERLIN,DEPT DERMATOL,BERLIN,GERMANY. GEORGETOWN UNIV,DEPT BIOL,MOLEC NEUROBIOL LAB,WASHINGTON,DC 20007. RP GAUDET, SJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 309,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK 37024] NR 34 TC 40 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1993 VL 101 IS 5 BP 660 EP 665 DI 10.1111/1523-1747.ep12371672 PG 6 WC Dermatology SC Dermatology GA ME694 UT WOS:A1993ME69400004 PM 8228325 ER PT J AU PUNNONEN, K DENNING, M LEE, E RHEE, SG YUSPA, SH AF PUNNONEN, K DENNING, M LEE, E RHEE, SG YUSPA, SH TI KERATINOCYTE DIFFERENTIATION IS ASSOCIATED WITH CHANGES IN THE EXPRESSION AND REGULATION OF PHOSPHOLIPASE-C ISOENZYMES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CALCIUM; TYROSINE PHOSPHORYLATION; BAPTA; PROTEIN KINASE-C ID PROTEIN-KINASE-C; INOSITOL PHOSPHATE-METABOLISM; CULTURED MURINE KERATINOCYTES; MOUSE EPIDERMAL-CELLS; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; PHORBOL ESTER; CALCIUM; INVITRO AB In murine keratinocytes, Ca++-induced terminal differentiation is accompanied by a rapid and sustained increase of inositol phosphates and diacylglycerol. Based on Western blotting analysis, basal keratinocytes cultured in 0.05 mM Ca++ medium express phospholipase C (PLC)-gamma1 predominantly and no detectable PLC-beta1. Differentiating keratinocytes cultured in 1.4 mM Ca++ express two- to threefold more PLC-gamma1 protein and PLC-delta1, but no detectable PLC-beta1. Although the amount of PLC-gamma1 and -delta1 protein increased, PLC-gamma1 and -delta1 mRNA decreased in differentiating cells. Thus the sustained rise of PLC activity induced by Ca++ in differentiating keratinocytes may be associated with higher amounts of both PLC-gamma1 and -delta1 in maturing cells, determined by a posttranscriptional mechanism. Tyrosine phosphate content in PLC-gamma1 was low in basal cells and did not change in cells exposed to 1.4 mM Ca++. However, genistein inhibited the increase in PLC activity induced by 1.4 mM Ca++. In contrast, transforming growth factor (TGF)alpha, which stimulates both PLC activity and growth in basal keratinocytes, increased tyrosine phosphorylation of PLC-gamma1. These results suggest that tyrosine phosphorylation of PLC-gamma1 by the epidermal growth factor (EGF) receptor is linked to stimulated proliferation, whereas stimulation of PLC activity by Ca++ is linked to keratinocyte differentiation and involves the action of a tyrosine kinase but not tyrosine phosphorylation of PLC-gamma1. Based on studies using the intracellular free Ca++ chelator BAPTA, a rise in intracellular free Ca++ was not required for stimulation of PLC activity by raising extracellular Ca++. Phorbol esters inhibited PLC stimulation by 1.4 mM Ca++ medium and increased serine phosphorylation of PLC-gamma1. Exogenous phosphatidylinositol-specific and phosphatidylcholine-specific bacterial PLC also inhibited endogenous inositol phosphate formation and increased endogenous diacylglycerol (DAG). Thus, direct serine phosphorylation of PLC-gamma1 by protein kinase C is associated with the inhibition of Ca++-mediated PLC stimulation. These results show that keratinocytes have multiple mechanisms to regulate PLC activity in response to a specific signal. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROD LAB, BLDG 37, ROOM 3B25, BETHESDA, MD 20892 USA. NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 59 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1993 VL 101 IS 5 BP 719 EP 726 DI 10.1111/1523-1747.ep12371682 PG 8 WC Dermatology SC Dermatology GA ME694 UT WOS:A1993ME69400014 PM 8228334 ER PT J AU WATERS, HL SEETHARAM, S SEIDMAN, MM KRAEMER, KH AF WATERS, HL SEETHARAM, S SEIDMAN, MM KRAEMER, KH TI ULTRAVIOLET HYPERMUTABILITY OF A SHUTTLE VECTOR PROPAGATED IN XERODERMA-PIGMENTOSUM VARIANT CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE DNA REPAIR; SKIN CANCER; SUPF TRANSFER RNA; LYMPHOBLASTOID CELLS ID DYSPLASTIC NEVUS SYNDROME; DNA-REPAIR; POINT MUTATIONS; ESCHERICHIA-COLI; UV-IRRADIATION; PLASMID; LIGHT; MUTAGENESIS; FIBROBLASTS; SPECTRUM AB Patients with the variant form of xeroderma pigmentosum (XP) have clinical Xp including a high frequency of skin cancer but, in contrast to the other forms of XP, have normal post-ultraviolet (UV) DNA excision repair and nearly normal post-UV survival. However, like excision repair-deficient XP cells, the XP variant cells are UV hypermutable. We used a UV-treated plasmid shuttle vector, pZ189, to examine the DNA repair defect in lymphoblastoid cells from an XP variant patient, XPPHBE, and a normal control. Plasmid repair, mutagenesis, and replication occur within transfected cells in a process dependent on the cells' repair capacity. With the XP variant cells post-UV, plasmid survival was normal with but there was an abnormally increased post-UV plasmid mutation frequency. Sequence analysis of the mutated plasmids revealed an increased frequency of plasmids with single base substitution mutations with the XP variant cells. As in earlier studies with UV mutagenesis, there was a predominance of G:C-->A:T base substitution mutations with plasmids recovered from both cell lines. The frequency of G:C-->C:G transversions was significantly higher with plasmids recovered from the XP variant cells than from normal cells. The location of mutations in the marker gene was non-random with different mutagenic hotspots found in plasmids recovered from the XP variant cells and from the normal cells. This study suggests that plasmid UV hypermutability in the presence of normal UV survival may be related to the increased UV skin cancer susceptibility of XP variant patients. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. OTSUKA PHARMACEUT CO LTD,ROCKVILLE,MD. FU Intramural NIH HHS [Z01 BC004517-31] NR 48 TC 64 Z9 64 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1993 VL 101 IS 5 BP 744 EP 748 DI 10.1111/1523-1747.ep12371686 PG 5 WC Dermatology SC Dermatology GA ME694 UT WOS:A1993ME69400018 PM 8228338 ER PT J AU PU, YM ZIFFER, H AF PU, YM ZIFFER, H TI SYNTHESIS OF 11-[H-3]-ARTEETHER, AN EXPERIMENTAL ANTIMALARIAL DRUG SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE ARTEETHER; ARTEMISININ; ANHYDRODIHYDROARTEMISININ; MALARIA ID QINGHAOSU ARTEMISININ; DERIVATIVES; ARTEETHER AB The triphenylphosphine hydrobromide-catalyzed addition of a proton from ethanol to anhydrodihydroartemisinin (5) has been employed for the synthesis of 2 and 4. Use of 1.5 equivalents of EtO2H or EtO3H yielded 11-[H-2]- or 11-[H-3]-beta-arteether as the major product. RP PU, YM (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 1993 VL 33 IS 11 BP 1013 EP 1018 DI 10.1002/jlcr.2580331104 PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA ME203 UT WOS:A1993ME20300003 ER PT J AU ZHU, G TORCHIA, DA BAX, A AF ZHU, G TORCHIA, DA BAX, A TI DISCRETE FOURIER TRANSFORMATION OF NMR SIGNALS - THE RELATIONSHIP BETWEEN SAMPLING DELAY-TIME AND SPECTRAL BASE-LINE SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Note ID OPTIMIZATION; SPECTROSCOPY; DISTORTION C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP ZHU, G (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 10 TC 30 Z9 30 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 NOV PY 1993 VL 105 IS 2 BP 219 EP 222 DI 10.1006/jmra.1993.1274 PG 4 WC Physics, Atomic, Molecular & Chemical SC Physics GA MF843 UT WOS:A1993MF84300012 ER PT J AU LAMB, ME AF LAMB, ME TI FATHERHOOD IN AMERICA - A HISTORY - GRISWOLD,RL SO JOURNAL OF MARRIAGE AND THE FAMILY LA English DT Book Review RP LAMB, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 3 PU NATL COUNCIL FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD NOV PY 1993 VL 55 IS 4 BP 1047 EP 1049 DI 10.2307/352786 PG 3 WC Family Studies; Sociology SC Family Studies; Sociology GA MK696 UT WOS:A1993MK69600023 ER PT J AU YIN, S TSAREV, SA PURCELL, RH EMERSON, SU AF YIN, S TSAREV, SA PURCELL, RH EMERSON, SU TI PARTIAL SEQUENCE COMPARISON OF 8 NEW CHINESE STRAINS OF HEPATITIS-E VIRUS SUGGESTS THE GENOME SEQUENCE IS RELATIVELY STABLE SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEV EPIDEMICS; PCR; GENETIC HETEROGENEITY ID NON-B HEPATITIS; TRANSMITTED NON-A; MOLECULAR-CLONING; PARTICLES; EPIDEMIC; RECOVERY; HEV AB Partial genomic sequences representing 420 nucleotides of a nonstructional region, 480 nucleotides of the putative RNA polymerase region, and 540 nucleotides of the structural region of epidemic-associated Chinese strains of hepatitis E virus (HEV) were obtained by direct sequencing of PCR-amplified DNA. Comparison with previously published HEV sequences showed a clear relatedness of all Chinese strains to each other and to a Pakistani strain (Sar-55). All eight Chinese strains examined had very similar sequences (98.5-99.8% homology) in the regions examined and were much closer to the Pakistani strain (Sar-55) (97.9-98.4% homology) than to the Burmese strain (92.5-93.3% homology). Sequence comparisons of the three genomic regions in the Chinese strains indicated that the RNA polymerase region was much more conserved than the other nonstructural region or the structural region. HEV isolates from three remote geographic regions of China had sequences closely related to each other. (C) 1993 Wiley-Liss, Inc. C1 INST MICROBIOL & EPIDEMIOL,BEIJING,PEOPLES R CHINA. RP YIN, S (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 200,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 35 Z9 42 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 1993 VL 41 IS 3 BP 230 EP 241 DI 10.1002/jmv.1890410311 PG 12 WC Virology SC Virology GA MD079 UT WOS:A1993MD07900010 PM 8263504 ER PT J AU RESHKIN, SJ LEE, SI GEORGE, JN TURNER, RJ AF RESHKIN, SJ LEE, SI GEORGE, JN TURNER, RJ TI IDENTIFICATION, CHARACTERIZATION AND PURIFICATION OF A 160 KD BUMETANIDE-BINDING GLYCOPROTEIN FROM THE RABBIT PAROTID SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE LOOP DIURETIC; SALIVARY GLAND; FLUID SECRETION; NA+-K+-CL- COTRANSPORT; ACINAR CELL; CHLORIDE SECRETION ID SHARK RECTAL GLAND; N-ACETYLGLUCOSAMINIDASE-F; CL COTRANSPORT PROTEIN; EHRLICH ASCITES-CELLS; NA/K/CL COTRANSPORTER; KIDNEY; PHOSPHORYLATION; MEMBRANES; SYSTEM AB We demonstrate the presence of a 160 kD protein in rabbit parotid basolateral membranes that can be labeled with the irreversible sulfhydryl reagent [C-14]-N-ethylmaleimide in a bumetanide-protectable fashion. The specificity of this labeling, and our previous evidence for the existence of an essential sulfhydryl group closely associated with the (bumetanide-binding site on the parotid Na+-K+-Cl- cotransporter J. Membrane Biol. 112:51-58, 1989), provide strong evidence that this protein is a part or all of the parotid bumetanide-binding site. When this protein is treated with endoglycosidase F/N-glycosidase F to remove N-linked oligosaccharides, its apparent molecular weight decreases to 135 kD. The pl of this deglycosylated protein is almost-equal-to 6.4. The bumetanide-binding protein was purified using two preparative electrophoresis steps. First, a Triton X-100 extract enriched in this protein was run on preparative electrophoresis to obtain fractions containing proteins in the 160 kD range. These were then deglycosylated with endoglycosidase F/N-glycosidase F and selected fractions were pooled and rerun on preparative electrophoresis to obtain a final 135 kD fraction. The enrichment of the bumetanide-binding protein in this final 135 kD fraction estimated from [C-14]-N-ethylmaleimide labeling was approximately 48 times relative to the starting membrane extract. Since the bumetanide-binding site represents approximately 2% of the total protein in this starting extract, this enrichment indicates a high degree of purity of this protein in the 135 kD fraction. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1A06,BETHESDA,MD 20892. YONSEI UNIV,COLL DENT,DEPT ORAL BIOL,8044 SEOUL,SOUTH KOREA. NR 26 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV PY 1993 VL 136 IS 2 BP 243 EP 251 DI 10.1007/BF02505766 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA MH770 UT WOS:A1993MH77000013 PM 8107077 ER PT J AU GEORGE, MS BREWERTON, TD HARDEN, RN AF GEORGE, MS BREWERTON, TD HARDEN, RN TI BULIMIA-NERVOSA IN OUTPATIENTS WITH MIGRAINE - A PILOT-STUDY SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Note ID META-CHLOROPHENYLPIPERAZINE; HEADACHE; RESPONSES; EPIDEMIOLOGY; FLUOXETINE; WOMEN C1 MED UNIV S CAROLINA,DEPT PSYCHIAT,EATING DISORDERS PROGRAM,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 2 Z9 2 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1993 VL 181 IS 11 BP 704 EP 706 DI 10.1097/00005053-199311000-00011 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MG197 UT WOS:A1993MG19700011 PM 8228954 ER PT J AU NELSON, PG FIELDS, RD YU, C LIU, Y AF NELSON, PG FIELDS, RD YU, C LIU, Y TI SYNAPSE ELIMINATION FROM THE MOUSE NEUROMUSCULAR-JUNCTION IN-VITRO - A NON-HEBBIAN ACTIVITY-DEPENDENT PROCESS SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE SYNAPSE ELIMINATION; NEUROMUSCULAR JUNCTION; HEBBIAN; PLASTICITY; CAMPENOT CHAMBER ID OCULAR DOMINANCE COLUMNS; RAT SYMPATHETIC NEURONS; SKELETAL-MUSCLE FIBERS; POLYNEURONAL INNERVATION; ELECTRICAL-ACTIVITY; SOLEUS MUSCLE; COMPETITIVE ELIMINATION; MULTIPLE INNERVATION; NEURITE OUTGROWTH; STRIATED-MUSCLE AB The effect of action potentials on elimination of mouse neuromuscular junctions (NMJ) was studied in a three-compartment cell culture preparation. Axons from superior cervical ganglion or ventral spinal cord neurons in two lateral compartments formed multiple neuromuscular junctions with muscle cells in a central compartment. The loss of synapses over a 2-7-day period was determined by serial electrophysiological recording and a functional assay. Electrical stimulation of axons from one side compartment during this period, using 30-Hz bursts of 2-s duration, repeated at 10-s intervals, caused a significant increase in synapse elimination compared to unstimulated cultures (p < 0.001). The extent of homosynaptic and heterosynaptic elimination was comparable, i.e., of the 226 functional synapses of each type studied, 111 (49%) of the synapses that had been stimulated were eliminated, and 87 (39%) of unstimulated synapses on the same muscle cells were eliminated. Also, simultaneous bilateral stimulation caused significantly greater elimination of synapses than unilateral stimulation (p < 0.005). These observations are contrary to the Hebbian hypothesis of synaptic plasticity. A spatial effect of stimulus-induced synapse elimination was also evident following simultaneous bilateral stimulation. Prior to stimulation, most muscle cells were innervated by axons from both side compartments, but after bilateral stimulation, muscle cells were predominantly unilaterally innervated by axons from the closer compartment. These experiments suggest that synapse elimination at the NMJ is an activity-dependent process, but it does not follow Hebbian or anti-Hebbian rules of synaptic plasticity. Rather, elimination is a consequence of postsynaptic activation and a function of location of the muscle cell relative to the neuron. An interaction between spatial and activity-dependent effects on synapse elimination could help produce optimal refinement of synaptic connections during postnatal development. (C) 1993 John Wiley & Sons, Inc.* RP NELSON, PG (reprint author), NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 61 TC 51 Z9 51 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV PY 1993 VL 24 IS 11 BP 1517 EP 1530 DI 10.1002/neu.480241106 PG 14 WC Neurosciences SC Neurosciences & Neurology GA MC012 UT WOS:A1993MC01200005 PM 8283186 ER PT J AU RHOADS, AR PARUI, R VU, ND CADOGAN, R WAGNER, PD AF RHOADS, AR PARUI, R VU, ND CADOGAN, R WAGNER, PD TI ATP-INDUCED SECRETION IN PC12-CELLS AND PHOTOAFFINITY-LABELING OF RECEPTORS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CATECHOLAMINES; RAT; EXTRACELLULAR ATP; PC12 CELLS; NOREPINEPHRINE RELEASE; P2 PURINERGIC RECEPTOR ID PIG VAS-DEFERENS; RAT MAST-CELLS; PC12 CELLS; PERTUSSIS-TOXIN; SMOOTH-MUSCLE; NOREPINEPHRINE SECRETION; CHROMAFFIN CELLS; CALCIUM INFLUX; PC-12 CELLS; G-PROTEIN AB Secretion of catecholamines by rat PC12 cells is strongly stimulated by extracellular ATP via a P2-type purinergic receptor. ATP-induced norepinephrine release was inhibited 80% when extracellular Ca2+ was absent. Only four nucleotides, ATP, ATPgammaS, benzoylbenzoyl ATP (BzATP), and 2-methylthio-ATP, gave substantial stimulation of norepinephrine release from PC12 cells. ATP-induced secretion was inhibited by Mg2+, and this inhibition was overcome by the addition of excess ATP suggesting that ATp4- was the active ligand. ATP-induced secretion of catecholamine release was enhanced by treatment of cells with pertussis toxin or 12-0-tetradecanoylphorbol 13-acetate. The stimulatory effects of 12-O-tetradecanoyl-phorbol 13-acetate and pertussis toxin on norepinephrine release were additive. After brief exposure of intact cells to the photoaffinity analog, [alpha-P-32]BzATP, two major proteins of 44 and 50 kDa and a minor protein of 97 kDa were labeled. An excess of ATPgammaS and BzATP but not GTP blocked labeling of the proteins by [P-32]BzATP. Labeling of the 50-kDa protein was more sensitive to competition by 2-methylthio-ATP than the other labeled proteins, suggesting that the 50-kDa protein represents the P2 receptor responsible for ATP-stimulated secretion in these cells. C1 NCI,BETHESDA,MD 20892. RP RHOADS, AR (reprint author), HOWARD UNIV,COLL MED,DEPT BIOCHEM & MOLEC BIOL,520 W ST NW,WASHINGTON,DC 20059, USA. NR 29 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1993 VL 61 IS 5 BP 1657 EP 1666 DI 10.1111/j.1471-4159.1993.tb09800.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MD350 UT WOS:A1993MD35000009 PM 8228985 ER PT J AU DRISCOLL, BF DEIBLER, GE LAW, MJ CRANE, AM AF DRISCOLL, BF DEIBLER, GE LAW, MJ CRANE, AM TI DAMAGE TO NEURONS IN CULTURE FOLLOWING MEDIUM CHANGE - ROLE OF GLUTAMINE AND EXTRACELLULAR GENERATION OF GLUTAMATE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MESENCEPHALIC CULTURES; MEDIUM CHANGE; EXCITOTOXICITY; GLUTAMATE; N-METHYL-D-ASPARTATE RECEPTOR; GLUTAMINASE; DOPAMINE ID CEREBRAL-ISCHEMIA; NEUROTOXICITY; RELEASE AB Changing the medium of primary cell cultures of CNS origin causes severe damage that is mediated via the N-methyl-D-aspartate (NMDA)-type of glutamate receptors and dependent on the presence of glutamine in the medium. Data presented here show that glutamine has two roles in culture damage: glutamine is contaminated with a small amount of glutamate, which is responsible for initiating culture damage, and glutamine is the source of the glutamate that is produced extracellularly in damaged cultures. The NMDA receptor plays a critical role minutes after medium change when the glutamate contaminating the glutamine binds to NMDA receptors; during this time, addition of a low level (10-20 muM) of 2-amino-5-phosphonovaleric acid can block most culture damage and the appearance of extracellular glutamate. A higher level (300 muM) of 2-amino-5-phosphonovaleric acid can protect cultures when added at much later times (30-60 min). Between 3 and 6 h after medium change, the concentration of extracellular glutamate starts to rise and accumulates until the end of the culture period (20 h). Medium removed from cultures at 3 h or later after medium change and incubated alone (i.e., with no cells) also continues to generate glutamate; filtration (0.22 mum pore size) or centrifugation (18,000 g) stops the appearance of this glutamate. 6-Diazo-5-OXO-L-norleucine, an inhibitor of the mitochondrial enzyme glutaminase, blocks the generation of glutamate. Mitochondria or mitochondrial fragments are probably released from the damaged cells and then convert extracellular glutamine to glutamate, resulting in generation of a high extracellular glutamate concentration. RP DRISCOLL, BF (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,BETHESDA,MD 20892, USA. NR 15 TC 52 Z9 52 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1993 VL 61 IS 5 BP 1795 EP 1800 DI 10.1111/j.1471-4159.1993.tb09818.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MD350 UT WOS:A1993MD35000027 PM 7901333 ER PT J AU WILLIAMS, WM RAPOPORT, SI AF WILLIAMS, WM RAPOPORT, SI TI ALTERED COMPOSITION OF CEREBRAL MICROVESSEL MEMBRANE PHOSPHOGLYCERIDES FROM SENESCENT MOUSE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MICROVESSELS; PHOSPHOLIPID; FATTY ACIDS; AGING; MOUSE ID BRAIN CAPILLARIES; LIPID-COMPOSITION; RATS; PROTECTION; CELLS; AGE AB Phosphoglyceride and fatty acid composition was determined in the cellular membranes of isolated cerebral microvessels and brain parenchymal cells (neurons and glia) taken from 10-, 20-, and 27-30-month-old C57BL6/NNIA mice. Lipids were extracted from each fraction and the fatty acid profiles of ethanolamine, choline, serine, and inositol phosphoglycerides analyzed by gas chromatography. The results suggest that membrane phosphoglycerides from cerebral microvessels are significantly more affected by the aging process than are those of the brain parenchyma. Relative percentage for fatty acids in cerebral microvessels indicate an overall decline in membrane unsaturation with a concomitant elevation in the level of saturation. The decline in unsaturation is reflected primarily in the loss of precursor fatty acids for arachidonic (18:2n-6 and 20:3n-6) and docosahexaenoic (20:5n-3 and 22:5n-3) acids. Levels of arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids in each phosphoglyceride remained unchanged with age; however, mol% for ethanolamine plasmalogen, a major source of these fatty acids, was significantly reduced in 27-30-month-old mice. Conversely, mol% for choline phosphoglyceride increased with age. The age-related changes in fatty acid profile for microvessel membrane phosphoglycerides are reflected by increased saturation/unsaturation ratios and decreased unsaturation indices. These parameters were not affected by aging in parenchymal membranes. RP WILLIAMS, WM (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892, USA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1993 VL 61 IS 5 BP 1843 EP 1849 DI 10.1111/j.1471-4159.1993.tb09825.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MD350 UT WOS:A1993MD35000034 PM 8228998 ER PT J AU CHEN, CC ANDRICH, MP SHELHAMER, J AF CHEN, CC ANDRICH, MP SHELHAMER, J TI ABNORMALITIES ON VENTILATION-PERFUSION LUNG SCANS INDUCED BY BRONCHOALVEOLAR LAVAGE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID FIBEROPTIC BRONCHOSCOPY; PNEUMONIA; DISEASE AB Studies were performed before and at varying times after lavage in 10 normal volunteers to assess whether bronchoalveolar lavage results in significant abnormalities on ventilation/perfusion lung scans and chest x-rays. Abnormal lung scans were obtained in six subjects, interpretable as intermediate (three scans), low (one scan) and very low (two scans) probability for pulmonary emboli. Defects varied from multisegmental to subsegmental in size, while chest x-rays were normal in all but one. Both the extent and frequency of defects tended to decrease with time; 24 hr after bronchoalveolar lavage only one of four subjects had a minimally abnormal scan. It is recommended that ventilation/perfusion lung scanning be delayed at least 24 hr following bronchoalveolar lavage to avoid problems in interpretation of defects which may merely be the result of the lavage. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP CHEN, CC (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BLDG 10,IC401,BETHESDA,MD 20892, USA. NR 12 TC 3 Z9 3 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 NOV PY 1993 VL 34 IS 11 BP 1854 EP 1858 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ME930 UT WOS:A1993ME93000007 PM 8229224 ER PT J AU GALLELLI, JF GROVES, MJ AF GALLELLI, JF GROVES, MJ TI USP PERSPECTIVES ON PARTICLE CONTAMINATION OF INJECTABLE PRODUCTS SO JOURNAL OF PARENTERAL SCIENCE AND TECHNOLOGY LA English DT Article AB It is widely recognized that the level of particulate matter in an injectable product is one measure of quality, directly reflecting the success with which the manufacturer applies good quality control. The current USP XXII 1990 limits for particulate matter derived from knowledge that goes back to the 1970s but does not reflect the quality of the product available today. This presentation will discuss the purpose and background of proposed new limits intended to be adopted in the USP 23 revision cycle. The limits tests are structured in two stages for both Large-Volume and Small-Volume Injections, effectively employing an improved light obscuration method as a screening procedure. Product which fails this stage is then evaluated by a second stage, filtration and microscopic examination using a considerably improved procedure in which all of the container contents are sampled (or pooled to 25 mL) and the filter examined episcopically. C1 NIH,DEPT PHARM,BETHESDA,MD 20892. UNIV ILLINOIS,COLL PHARM,INST TB RES,CHICAGO,IL 60680. NR 3 TC 3 Z9 3 U1 0 U2 1 PU PARENTERAL DRUG ASSOC, INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE, 620, BETHESDA, MD 20814 SN 0279-7976 J9 J PARENT SCI TECHN PD NOV-DEC PY 1993 VL 47 IS 6 BP 289 EP 292 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MY208 UT WOS:A1993MY20800005 PM 8120733 ER PT J AU HORBAR, JD WRIGHT, LL SOLL, RF WRIGHT, EC FANAROFF, AA KORONES, SB SHANKARAN, S OH, W FLETCHER, BD BAUER, CR TYSON, JE LEMONS, JA DONOVAN, EF STOLL, BJ STEVENSON, DD PAPILE, LA PHILIPS, J POLAND, RL TSANG, RC LITTLE, G BAIN, RP FOLEY, KA BANDSTRA, E MALLOY, M KENNEDY, K OSTREA, E EHRENKRAN, R HACK, M EDWARDS, W BRUMLEY, GW YOUNES, N DENNE, SC YAFFE, SJ BADA, H LUCEY, JF STONESTREET, B GROSS, I AF HORBAR, JD WRIGHT, LL SOLL, RF WRIGHT, EC FANAROFF, AA KORONES, SB SHANKARAN, S OH, W FLETCHER, BD BAUER, CR TYSON, JE LEMONS, JA DONOVAN, EF STOLL, BJ STEVENSON, DD PAPILE, LA PHILIPS, J POLAND, RL TSANG, RC LITTLE, G BAIN, RP FOLEY, KA BANDSTRA, E MALLOY, M KENNEDY, K OSTREA, E EHRENKRAN, R HACK, M EDWARDS, W BRUMLEY, GW YOUNES, N DENNE, SC YAFFE, SJ BADA, H LUCEY, JF STONESTREET, B GROSS, I TI A MULTICENTER RANDOMIZED TRIAL COMPARING 2 SURFACTANTS FOR THE TREATMENT OF NEONATAL RESPIRATORY-DISTRESS SYNDROME SO JOURNAL OF PEDIATRICS LA English DT Article ID HYALINE-MEMBRANE DISEASE; BOVINE SURFACTANT; CLINICAL-TRIAL; SYNTHETIC SURFACTANT; PREMATURE-INFANTS; DOUBLE-BLIND; REPLACEMENT THERAPY; FINAL ANALYSIS; PREVENTION; BIRTH AB Objective: To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. Design: Multicenter randomized trial. Setting: Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients: Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. Interventions: Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308). Main outcome measures: The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment. C1 NICHHD, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, CTR BIOSTAT, WASHINGTON, DC 20052 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. UNIV TENNESSEE, KNOXVILLE, TN 37996 USA. WAYNE STATE UNIV, DETROIT, MI 48202 USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. UNIV MIAMI, MIAMI, FL 33152 USA. UNIV TEXAS, SW MED CTR, DALLAS, TX 75230 USA. INDIANA UNIV, INDIANAPOLIS, IN 46204 USA. UNIV CINCINNATI, CINCINNATI, OH 45221 USA. EMORY UNIV, ATLANTA, GA 30322 USA. STANFORD UNIV, PALO ALTO, CA 94304 USA. UNIV NEW MEXICO, ALBUQUERQUE, NM 87131 USA. UNIV ALABAMA, BIRMINGHAM, AL 35294 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. DARTMOUTH COLL, HITCHCOCK MED CTR, HANOVER, NH 03756 USA. YALE UNIV, NEW HAVEN, CT 06520 USA. RP HORBAR, JD (reprint author), UNIV VERMONT, BURLINGTON, VT 05405 USA. FU NICHD NIH HHS [U10 HD21466, U10 HD21364, U01 HD19897] NR 41 TC 122 Z9 125 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1993 VL 123 IS 5 BP 757 EP 766 DI 10.1016/S0022-3476(05)80856-X PG 10 WC Pediatrics SC Pediatrics GA MF096 UT WOS:A1993MF09600016 PM 8229487 ER PT J AU SZALLASI, A GOSO, C BLUMBERG, PM MANZINI, S AF SZALLASI, A GOSO, C BLUMBERG, PM MANZINI, S TI COMPETITIVE-INHIBITION BY CAPSAZEPINE OF [H-3] RESINIFERATOXIN BINDING TO CENTRAL (SPINAL-CORD AND DORSAL-ROOT GANGLIA) AND PERIPHERAL (URINARY-BLADDER AND AIRWAYS) VANILLOID (CAPSAICIN) RECEPTORS IN THE RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PRIMARY AFFERENT NEURONS; TOPICAL CAPSAICIN; SENSORY NERVES; RUTHENIUM RED; RESINIFERATOXIN; ANTAGONIST; ANALOGS; DESENSITIZATION; DISORDERS; LEAKAGE AB Capsazepine was reported to block capsaicin- and resiniferatoxin (RTX)-induced responses both in vivo and in vitro with Schild plots suggesting a competitive mechanism of action. We have used the [H-3]RTX binding assay, thought to represent the vanilloid (capsaicin) receptor, to explore the inhibitory mechanism of capsazepine at the receptor level in the rat. In competition assays, capsazepine inhibited [H-3]RTX binding by spinal cord, dorsal root ganglion (DRG) and urinary bladder membranes with similar K(i) values of 4.0 +/- 0.3, 3.5 +/- 0.5 and 5.0 +/- 1.0 muM (mean +/- S.E.M.; three determinations), respectively. By contrast, capsazepine was 35- to 50-fold more potent for inhibiting specific [H-3]RTX binding in the airways (K(i) = 0.12 +/- 0.02 muM; mean +/- S.E.M.; four determinations). In experiments in which the concentration of [H-3]RTX was varied, 10 muM capsazepine reduced the affinity of the vanilloid receptor expressed by DRG and spinal cord membranes for [H-3]RTX from 15 +/- 3 to 43 +/- 5 pM, and from 20 +/- 3 to 80 +/- 5 pM (mean +/- S.E.M.; three determinations), respectively, without a measurable change in B(max) or in cooperativity index; these shifts in affinity yield K(i) values of 5.2 and 3.3 muM for DRG and spinal cord membranes, respectively. Capsaicin inhibited [H-3]RTX binding by spinal cord, DRG and urinary bladder membranes with a 6- to 13-fold higher potency than did capsazepine; the K(i) values were 0.3 +/- 0.1, 0.6 +/- 0.4 and 0.5 +/-0.2 muM (mean +/- S.E.M.; three determinations), respectively. By contrast, in the airways capsaicin and capsazepine competed with equal potency for specific [H-3]RTX binding sites (K(i) values were 0.12 +/- 0.02 muM for capsazepine and 0.14 +/- 0.10 muM for capsaicin; mean +/- S.E.M.; three determinations). Our results confirm the competitive mechanism of action of capsazepine and, in addition, suggest heterogeneity in the structure-activity relations of vanilloid receptors in different tissues of the rat. C1 MENARINI SUD,DEPT PHARMACOL,POMEZIA,ITALY. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 36 TC 59 Z9 62 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 NOV PY 1993 VL 267 IS 2 BP 728 EP 733 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH941 UT WOS:A1993MH94100024 PM 8246148 ER PT J AU KIM, CS PRITCHARD, JB AF KIM, CS PRITCHARD, JB TI TRANSPORT OF 2,4,5-TRICHLOROPHENOXYACETIC ACID ACROSS THE BLOOD-CEREBROSPINAL FLUID BARRIER OF THE RABBIT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CENTRAL NERVOUS-SYSTEM; CHOROID-PLEXUS; 2,4-DICHLOROPHENOXYACETIC ACID; QUINOLINIC ACID; REYES-SYNDROME; RAT-BRAIN; 2,4-D; ACCUMULATION; METABOLITES; PHARMACOLOGY AB Transport of the anionic herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) across the blood-cerebrospinal fluid barrier was investigated using the isolated choroid plexus of the adult rabbit in vitro and ventriculocisternal perfusion in vivo. In vitro, 2,4,5-T transport was effective, with tissue concentrations 20 times those in the medium after only 5 min of incubation with 1 muM 2,4,5-T. The tissue to medium ratios reached steady state by 20 min at approximately 45-fold. Uptake was energy dependent and inhibited by ouabain, phloridzin and several organic anions (probenecid, 2,4-dichlorophenoxyacetic acid and octanoate). Neither tyrosine (transported by a separate system) nor the neurotoxin, quinolinic acid, inhibited 2,4,5-T transport. Kinetic analysis yielded an apparent K(m) of 58 muM and V(max) of 111 nmol g-1 min-1 in the lateral ventricular choroid plexus with similar values (57 muM and 87 nmol g-1 min-1) in the fourth ventricular plexus. In vivo, the steady-state clearance of 2,4,5-T from the cerebrospinal fluid exceeded that of inulin and was reduced in a dose-dependent fashion by 2,4-dichlorophenoxyacetic acid and probenecid. Together, these data indicate that 2,4,5-T is cleared from the brain and cerebrospinal fluid by the organic anion transport system and that alterations in such transport may have a significant impact on the toxicity of this agent in the central nervous system. C1 UNIV N CAROLINA,SCH MED,DEPT NEUROL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,SCH MED,BIOL SCI RES CTR,CHAPEL HILL,NC 27514. NIEHS,COMPARAT MEMBRANE PHARMACOL SECT,CELLULAR & MOLEC PHARMACOL,RES TRIANGLE PK,NC 27709. FU NICHD NIH HHS [HD-03110]; NIEHS NIH HHS [ES-03458] NR 52 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1993 VL 267 IS 2 BP 751 EP 757 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH941 UT WOS:A1993MH94100027 PM 8246151 ER PT J AU COMER, SD MCNUTT, RW CHANG, KJ DECOSTA, BR MOSBERG, HI WOODS, JH AF COMER, SD MCNUTT, RW CHANG, KJ DECOSTA, BR MOSBERG, HI WOODS, JH TI DISCRIMINATIVE STIMULUS EFFECTS OF BW373U86 - A NONPEPTIDE LIGAND WITH SELECTIVITY FOR DELTA-OPIOID RECEPTORS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID OPIATE RECEPTORS; RHESUS-MONKEYS; KAPPA-OPIOIDS; MORPHINE; PIGEONS; PEPTIDES; ETHYLKETOCYCLAZOCINE; ENKEPHALINS; SPECIFICITY; ANTAGONIST AB Several opioid agonists were evaluated in pigeons trained to discriminate i.m. injections of sterile water from either the mu agonist morphine (5.6 mg/kg), the kappa agonist bremazocine (0.032mg/kg) or (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-di-methyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86; 0.56 mg/kg). Pigeons were trained to peck one of two keys on a fixed-ratio 20 schedule for food reinforcement. The pattern of substitution of mu, kappa and delta selective agonists in the three groups of birds suggested that the discriminative stimulus effects of morphine, bremazocine and BW373U86 were different; however, a component of the discriminative stimulus effects of BW373U86 appeared to be shared with morphine. Apparent pA2 values for naltrexone with morphine, bremazocine and BW373U86 were 7.6, 6.8 and 6.3, respectively. The apparent pA2 value for naltrindole with BW373U86 was 8.3. Naltrindole (1 0.0 mg/kg) produced a 3-fold shift to the right in the dose-effect curve for morphine but did not antagonize bremazocine. Although results from the substitution experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1000-fold more potent and naltrexone was 30-fold less potent in antagonizing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors. C1 UNIV MICHIGAN,DEPT MED CHEM,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. BURROUGHS WELLCOME CO,DIV ORGAN CHEM,RES TRIANGLE PK,NC 27709. BURROUGHS WELLCOME CO,DIV CELL BIOL,RES TRIANGLE PK,NC 27709. NIDDKD,BETHESDA,MD. FU NIDA NIH HHS [DA 00254] NR 30 TC 51 Z9 52 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1993 VL 267 IS 2 BP 866 EP 874 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH941 UT WOS:A1993MH94100042 PM 8246161 ER PT J AU COMER, SD HOENICKE, EM SABLE, AI MCNUTT, RW CHANG, KJ DECOSTA, BR MOSBERG, HI WOODS, JH AF COMER, SD HOENICKE, EM SABLE, AI MCNUTT, RW CHANG, KJ DECOSTA, BR MOSBERG, HI WOODS, JH TI CONVULSIVE EFFECTS OF SYSTEMIC ADMINISTRATION OF THE DELTA-OPIOID AGONIST BW373U86 IN MICE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT CEREBROSPINAL-FLUID; ELECTROCONVULSIVE SHOCK; DIFFERENTIAL ANTAGONISM; ENDOGENOUS OPIOIDS; RECEPTOR SUBTYPES; INDUCED SEIZURES; NALTRINDOLE; PEPTIDES; ENKEPHALIN; MORPHINE AB A systemically active, nonpeptidic delta receptor-selective agonist, (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), produced a brief, nonlethal convulsion in mice. The behavioral pattern of convulsion produced by pentylenetetrazol was similar to that produced by systemic administration of BW373U86. Although several episodes of convulsion occurred with pentylenetetrazol, BWB373U86 produced a single, brief episode. Naltrexone (10.0 and 100 mg/kg) and naltrindole (1.0, 3.2 and 10.0 mg/kg), but not midazolam (0.32 mg/kg), produced dose-dependent rightward shifts in the potency of BW373U86 to induce a convulsion. A dose of 3.2 mg/kg of midazolam completely eliminated convulsions induced by BW373U86. Midazolam (0.32 and 3.2 mg/kg), but not naltrindole (3.2 and 32.0 mg/kg), produced parallel rightward shifts in the pentylenetetrazol dose-effect curve. Pretreatment with a single injection of BW373U86 (3.2, 10.0, 32.0 or 100 mg/kg) produced a dose-related reduction in the capacity of BW373U86 to induce a second convulsion. Recovery of sensitivity to BW373U86 did not return to control levels for up to 2 weeks after pretreatment with a single injection of 32.0 mg/kg of BW373U86. Naltrindole (3.2 mg/kg) administered within 1 hr, but not at 2 hr, after a pretreatment dose of 1 0.0 mg/kg of BW373U86 prevented the refractoriness (tolerance) induced by the single dose of BW373U86. These data suggest that the convulsions as well as the tolerance induced by BW373U86 were initiated through delta opioid receptors. C1 UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT MED CHEM,ANN ARBOR,MI 48109. BURROUGHS WELLCOME CO,DIV ORGAN CHEM,RES TRIANGLE PK,NC 27709. BURROUGHS WELLCOME CO,DIV CELL BIOL,RES TRIANGLE PK,NC 27709. NIDDKO,BETHESDA,MD. RP COMER, SD (reprint author), UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109, USA. FU NIDA NIH HHS [DA 00254] NR 38 TC 91 Z9 91 U1 0 U2 4 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 NOV PY 1993 VL 267 IS 2 BP 888 EP 895 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH941 UT WOS:A1993MH94100045 PM 8246164 ER PT J AU IMAOKA, S WEDLUND, PJ OGAWA, H KIMURA, S GONZALEZ, FJ KIM, HY AF IMAOKA, S WEDLUND, PJ OGAWA, H KIMURA, S GONZALEZ, FJ KIM, HY TI IDENTIFICATION OF CYP2C23 EXPRESSED IN RAT-KIDNEY AS AN ARACHIDONIC-ACID EPOXYGENASE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIVER MESSENGER-RNA; EPOXYEICOSATRIENOIC ACIDS; OMEGA-HYDROXYLATION; CYTOCHROME-P-450; (OMEGA-1)-HYDROXYLATION; SEQUENCE; CORTEX; CDNA AB A cDNA was isolated from a rat kidney cDNA library using mixed probes of CYP (cytochrome P450) 2C6, 2C7, 2C8, 2C9 and 2C18 cDNAs. The 3'-terminal and 5'-terminal regions of the cDNA were sequenced and were identical with those of cytochrome P450 2C23 (CYP2C23) except for a one-base deletion and a one-base addition in coding region. These changes caused a frame shift and changed the deduced amino acid sequence relative to the previously published sequence. This cDNA was expressed using a baculovirus expression system, and the resultant P450 had a lambda(max) of 450 nm when reduced and complexed with carbon monoxide. Specific content of the expressed P450 ranged from 0.27 to 0.43 nmol/mg of cell lysate protein. Arachidonic acid metabolism catalyzed by expressed CYP2C23 indicated that CYP2C23 efficiently produced epoxyeicosatrienoic acids (EETs). These EETs were characterized further by gas-liquid chromatography/negative ion chemical ionization mass spectrometry (GC/NCIMS) and were found to include 8,9-EET, 11,12-EET and 14,15-EET in a ratio of 1:2:1. No 5,6-EET was detected. A low rate of lauric acid hydroxylation at the (omega-1)-position was found, but the enzyme was unable to metabolize prostaglandin E1. These studies suggest that CYP2C23 is responsible, in part, for the production of EETs in rat kidney. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD. NR 18 TC 41 Z9 43 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1993 VL 267 IS 2 BP 1012 EP 1016 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH941 UT WOS:A1993MH94100060 PM 8246128 ER PT J AU JANCZEWSKI, AM LAKATTA, EG AF JANCZEWSKI, AM LAKATTA, EG TI BUFFERING OF CALCIUM INFLUX BY SARCOPLASMIC-RETICULUM DURING THE ACTION-POTENTIAL IN GUINEA-PIG VENTRICULAR MYOCYTES SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CARDIAC PURKINJE-FIBERS; NA-CA EXCHANGE; INWARD CURRENT; INTRACELLULAR CALCIUM; MEMBRANE CURRENTS; ATRIAL MYOCYTES; INDUCED RELEASE; MUSCLE-CELLS; CAFFEINE; CONTRACTION AB 1. Intracellular [Ca2+] ([Ca2+]i) transients, monitored by the fluorescent Ca2+ indicator, indo-1, and twitch contractions elicited by action potentials, by voltage clamp pulses or by rapid, brief pulses of caffeine, were measured in guinea-pig single ventricular myocytes. Experiments were designed to determine whether and to what extent the trans-sarcolemmal Ca2+ influx is immediately sequestered by the sarcoplasmic reticulum (SR). 2. Rapid, brief (100-200 ms) pulses of caffeine onto a rested myocyte elicited a [Ca2+]i transient and a contraction. Following exposure to specific SR inhibitors, ryanodine (100 nM) or thapsigargin (200 nM), the rapid application of caffeine onto a rested myocyte failed to elicit changes in [Ca2+]i or in cell length, indicating that caffeine increases [Ca2+]i by specifically discharging Ca2+ from the SR. In the absence of these inhibitors, a second pulse of caffeine, within 3 min following a prior pulse, failed to elicit a [Ca2+]i transient or contraction, indicating that a caffeine pulse depletes the SR releasable Ca2+ pool. 3. Following Ca2+ depletion of the SR by double caffeine pulses at rest, an electrical stimulation elicited a slow increase in [Ca2+]i, and, after a delay, a small, slow twitch contraction. The simultaneous application of caffeine and electrical stimulation of cells in which the SR was Ca2+ depleted elicited [Ca2+]i transients with an increased rate of rise and a larger amplitude (53 +/- 8 and 63 +/- 9 % respectively; mean +/- S.E.M. , n = 21) than those elicited by electrical stimulation alone. 4. Whether caffeine affected the L-type calcium current (I(Ca)) elicited by electrical stimulation was determined under whole-cell voltage clamp. A caffeine pulse delivered at the onset of a depolarizing voltage clamp step also increased the rates of rise and the amplitudes of the [Ca2+]i transients and twitch contractions in cells in which the SR was depleted of Ca2+. However, Ca2+ influx via I(Ca) decreased when caffeine was pulsed in conjunction with the voltage clamp, as the peak I(Ca) was either unchanged or decreased while its inactivation was consistently accelerated. 5. Because the stimulation-dependent trans-sarcolemmal Ca2+ influx via I(Ca) is not increased by a caffeine pulse, the augmentation of the rates of rise and the amplitudes of the electrically stimulated [Ca2+]i transients by caffeine pulsed in conjunction with the electrical stimulation in cells in which the SR had been depleted of Ca2+ indicates that a port ion of Ca2+ influx during depolarization in the absence of caffeine is rapidly buffered by the SR. Accordingly, the selective inhibition of the SR Ca2+ uptake by thapsigargin also increased the rates of rise and the amplitudes of the post-rest [Ca2+]i transients elicited by electrical stimulation by 65 +/- 21 and 28 +/- 8 % respectively. The rates of rise and the amplitudes of the accompanying twitch contractions were increased by 57 +/- 21 and 112 +/- 27 %, respectively (n = 7). 6. The caffeine-dependent augmentation of the electrically stimulated [Ca2+]i transients in cells in which the SR had been depleted of Ca2+ decreased if the caffeine pulse was delivered after a delay following electrical stimulation. This suggests that the rapid sequestration of the transmembrane Ca2+ influx by the SR during electrical stimulation is followed by SR Ca'' release during the same depolarization. 7. We conclude that during a single post-rest stimulation of guinea-pig ventricular myocytes, at least 50 % of Ca2+ entering the cell during the action potential is rapidly sequestered by the SR and that part of this Ca2+ is subsequently released from the SR during the same cardiac cycle. RP JANCZEWSKI, AM (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 53 TC 54 Z9 55 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 1993 VL 471 BP 343 EP 363 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA MK551 UT WOS:A1993MK55100018 PM 8120810 ER PT J AU MCCARTHY, GR GUCKES, AD AF MCCARTHY, GR GUCKES, AD TI PREVENTING BACTERIAL-COLONIZATION ASSOCIATED WITH 2 TYPES OF IMPLANT ABUTMENTS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Note C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP MCCARTHY, GR (reprint author), NIDR,PATIENT CARE & CLIN STUDIES SECT,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD NOV PY 1993 VL 70 IS 5 BP 479 EP 479 DI 10.1016/0022-3913(93)90089-7 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ME699 UT WOS:A1993ME69900019 PM 8254555 ER PT J AU CONWAY, JF TRUS, BL BOOY, FP NEWCOMB, WW BROWN, JC STEVEN, AC AF CONWAY, JF TRUS, BL BOOY, FP NEWCOMB, WW BROWN, JC STEVEN, AC TI THE EFFECTS OF RADIATION-DAMAGE ON THE STRUCTURE OF FROZEN-HYDRATED HSV-1 CAPSIDS SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; CRYO-ELECTRON-MICROSCOPY; 3-DIMENSIONAL STRUCTURE; SIMIAN VIRUS-40; ICE; MICROGRAPHS; SPECIMENS; CRYSTAL; RECONSTRUCTION; ENVELOPE AB Radiation damage imposes stringent limits on the information content of electron micrographs of biological specimens. In this study, we have investigated its effects on frozen, hydrated specimens and three-dimensional reconstructions calculated from cryomicrographs using capsids of herpes simplex virus as a model system. Multiple-exposure series of micrographs of both B-capsids (which contain no DNA) and C-capsids (which are fully packaged) were recorded and reconstructions were calculated from the first exposures, corresponding to a cumulative electron dose of 6-7 e(-)/Angstrom(2), and from later exposures (25-40 e(-)/Angstrom(2)). Experimental procedures were standardized to ensure that perceived changes in the micrographs and reconstructions would be attributable to radiation damage alone. The effects of the higher doses in both the micrographs and the reconstructions were expressed as a progressive blurring of the finer details, corresponding to a delocalization of structure in the ice-embedded specimens. The resolutions of the reconstructions were quantified according to a form of the Fourier ring correlation coefficient criterion, according to which the first-exposure reconstructions had resolutions of 30-36 Angstrom. The fifth-exposure B-capsid reconstruction had comparable nominal resolution, although it exhibited progressively lower correlations at higher spatial frequencies. Qualitatively similar changes in the series of C-capsid reconstructions were observed although they were more pronounced, presumably because these micrographs had lower contrast and signal-to-noise ratios. We infer that the observed changes in the images and reconstructions and the concomitant loss in contrast in the immediate vicinity of the capsid surface may reflect radiation-induced perturbation of molecular structure and/or the release of peptide fragments. Nevertheless, the observed changes are relatively subtle, at least at the operational resolution of this study; overall, our results support earlier indications (M. F. Schmid et al. J. Struct. Biol. 108, 62-68, 1992) that prospects are quite good for tilt-series reconstructions from cryoelectron micrographs, including six to eight views of the same specimen. (C) 1993 Academic Press, Inc. C1 NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 45 TC 96 Z9 97 U1 2 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD NOV-DEC PY 1993 VL 111 IS 3 BP 222 EP 233 DI 10.1006/jsbi.1993.1052 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NG948 UT WOS:A1993NG94800006 PM 8003383 ER PT J AU MCLELLAN, AT GROSSMAN, DS BLAINE, JD HAVERKOS, HW AF MCLELLAN, AT GROSSMAN, DS BLAINE, JD HAVERKOS, HW TI ACUPUNCTURE TREATMENT FOR DRUG-ABUSE - A TECHNICAL REVIEW SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE ACUPUNCTURE; ELECTROACUPUNCTURE; DETOXIFICATION; REHABILITATION; RELAPSE PREVENTION ID DETOXIFICATION AB Conflicting opinions exist regarding the efficacy of acupuncture for the treatment of substance abuse. On October 23, 1991, the National institute on Drug Abuse (NIDA) sponsored a technical review to discuss this issue. The purpose of the meeting was to review the current status of research regarding acupuncture treatment for drug abuse and to propose directions for future studies. This report represents a summary of the meeting which consisted of presentations by individuals currently involved in acupuncture treatment and discussions by a panel of experts in the field of substance abuse treatment research. C1 NIDA,DIV CLIN RES,ROCKVILLE,MD 20857. PENN VET ADM CTR STUDIES ADDICT,PHILADELPHIA,PA. NR 10 TC 40 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD NOV-DEC PY 1993 VL 10 IS 6 BP 569 EP 576 DI 10.1016/0740-5472(93)90061-6 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA MM419 UT WOS:A1993MM41900010 PM 8308942 ER PT J AU SHAFFER, D DULCAN, MK OFFORD, DR AF SHAFFER, D DULCAN, MK OFFORD, DR TI HOW CAN EPIDEMIOLOGY IMPROVE MENTAL-HEALTH-SERVICES FOR CHILDREN AND ADOLESCENTS - DISCUSSION SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID GLOBAL ASSESSMENT SCALE C1 COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. NIMH,WASHINGTON,DC 20032. MCMASTER UNIV,DIV CHILD PSYCHIAT,HAMILTON L8S 4L8,ONTARIO,CANADA. CHEDOKE CHILD & FAMILY CTR,HAMILTON L8N 3L6,ONTARIO,CANADA. HLTH & WELF CANADA,OTTAWA K1A 0L2,ONTARIO,CANADA. RP SHAFFER, D (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,DIV CHILD PSYCHIAT,722 W 168TH ST,BOX 78,NEW YORK,NY 10032, USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1993 VL 32 IS 6 BP 1114 EP 1117 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MD603 UT WOS:A1993MD60300003 ER PT J AU CAMPBELL, M ANDERSON, LT SMALL, AM ADAMS, P GONZALEZ, NM ERNST, M AF CAMPBELL, M ANDERSON, LT SMALL, AM ADAMS, P GONZALEZ, NM ERNST, M TI NALTREXONE IN AUTISTIC-CHILDREN - BEHAVIORAL SYMPTOMS AND ATTENTIONAL LEARNING SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE NALTREXONE; AUTISM; DISCRIMINATION LEARNING; SELF-INJURIOUS BEHAVIOR ID SELF-INJURIOUS-BEHAVIOR; INFANTILE-AUTISM; DOUBLE-BLIND; HALOPERIDOL; DYSKINESIAS; WITHDRAWAL; REVERSAL; THERAPY AB Objective: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. Method: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. Conclusion: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior. C1 COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. CORNELL UNIV,MED CTR,NEW YORK HOSP,COLL MED,WESTCHESTER DIV,NEW YORK,NY 10021. NIMH,ADAMHA,WASHINGTON,DC 20032. RP CAMPBELL, M (reprint author), NYU MED CTR,DEPT PSYCHIAT,550 1ST AVE,NEW YORK,NY 10016, USA. FU NIMH NIH HHS [NIMH MH-18915, NIMH MH-32212] NR 45 TC 107 Z9 109 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1993 VL 32 IS 6 BP 1283 EP 1291 DI 10.1097/00004583-199311000-00024 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MD603 UT WOS:A1993MD60300025 PM 8282676 ER PT J AU BERTHOLD, CW SCHNEIDER, A DIONNE, RA AF BERTHOLD, CW SCHNEIDER, A DIONNE, RA TI USING TRIAZOLAM TO REDUCE DENTAL ANXIETY SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID PLACEBO; FLURAZEPAM; DIAZEPAM; SURGERY; MEMORY; SLEEP; DRUG; PREMEDICATION; ZOPICLONE; LORAZEPAM AB Triazolam, commonly prescribed to treat insomnia, also can be used to reduce dental anxiety. Despite controversial reports in the lay press, triazolam can be used safely at low doses for short periods. The authors review research concerning the drug's safety and discuss its use in dentistry. C1 NIH,CLIN PHARMACOL UNIT,BLDG 10,ROOM 1N-103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 55 TC 8 Z9 9 U1 1 U2 1 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 NOV PY 1993 VL 124 IS 11 BP 58 EP 64 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA MG952 UT WOS:A1993MG95200012 PM 8227774 ER PT J AU GIFT, HC BHAT, M AF GIFT, HC BHAT, M TI DENTAL VISITS FOR OROFACIAL INJURY - DEFINING THE DENTISTS ROLE SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB There were an estimated 5.9 million episodes of care for orofacial trauma in the U.S. private practice sector in 1991. More than 4 million were seen by general dental practitioners, the rest by specialists. An in-depth understanding of the injuries and the extent and cost of the care could establish a focused injury prevention strategy. C1 NIDR,CRANIOFACIAL DEV & DISORDERS PROGRAM,BETHESDA,MD 20892. RP GIFT, HC (reprint author), NIDR,DIS PREVENT & HLTH PROMOT BRANCH,EPIDEMIOL & ORAL DIS PROGRAM,BETHESDA,MD 20892, USA. NR 11 TC 4 Z9 4 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 NOV PY 1993 VL 124 IS 11 BP 92 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA MG952 UT WOS:A1993MG95200017 PM 7901253 ER PT J AU THIBAULT, P ALEXANDER, AJ BOYD, RK TOMER, KB AF THIBAULT, P ALEXANDER, AJ BOYD, RK TOMER, KB TI DELAYED DISSOCIATION SPECTRA OF SURVIVOR IONS FROM HIGH-ENERGY COLLISIONAL ACTIVATION SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID RESOLVED MASS-SPECTROMETRY; NORMAL-BUTYLBENZENE IONS; INITIAL KINETIC-ENERGY; TARGET GAS EXCITATION; POLYATOMIC IONS; INDUCED DECOMPOSITION; INTERNAL ENERGY; ANGULAR-DISTRIBUTION; OBSERVATION ANGLE; MOLECULAR ION AB Collisional activation (CA) of large ions at kiloelectronvolt energies is accompanied by unexpectedly large losses of translational energy, which vary with the nature of the collision gas. Previous investigations have concentrated upon subsequent fragmentations occurring within a time window covering a few mus immediately following collision, using mass-analyzed ion kinetic energy spectrometry. In the present work, survivor ions were selected for specified values of translational energy loss, and their internal energy contents assessed via their subsequent unimolecular fragmentation reactions within a later time window. Beam collimation was also applied when circumstances permitted to impose angular selection, thus minimizing cross talk between effects of collisional scattering and energy dispersion. It was shown that internal excitation of the reactant ion can account for only a small fraction of the observed loss of translational energy. The recoil energy of the target is thus the principal sink for the translational energy loss, since the latter was always chosen to be less than the lowest excitation energy of the target. This conclusion is shown to be consistent with theoretical models of the CA process. The practical implications of these conclusions for CA of large ions at kiloelectronvolt energies are discussed. C1 NATL RES COUNCIL CANADA,ATLANTIC REG LAB,INST MARINE BIOSCI,1411 OXFORD ST,HALIFAX B3H 3Z1,NS,CANADA. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 51 TC 31 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 1993 VL 4 IS 11 BP 845 EP 854 DI 10.1016/1044-0305(93)87002-T PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA MF087 UT WOS:A1993MF08700002 PM 24227528 ER PT J AU LEVEY, AS GREENE, T SCHLUCHTER, MD CLEARY, PA TESCHAN, PE LORENZ, RA MOLITCH, ME MITCH, WE SIEBERT, C HALL, PM STEFFES, MW AF LEVEY, AS GREENE, T SCHLUCHTER, MD CLEARY, PA TESCHAN, PE LORENZ, RA MOLITCH, ME MITCH, WE SIEBERT, C HALL, PM STEFFES, MW TI GLOMERULAR-FILTRATION RATE MEASUREMENTS IN CLINICAL-TRIALS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE RENAL FUNCTION; GFR; DIABETES; CHRONIC RENAL DISEASE; CLINICAL TRIAL ID RENAL-DISEASE; SUBCUTANEOUS INJECTION; INULIN; IOTHALAMATE; CLEARANCE AB To assess the utility and precision of GFR measurements in multicenter trials, the test performance and variability of GFR were analyzed in 2,250 patients enrolled in 44 clinical centers participating in either the Modification of Diet in Renal Disease (MDRD) Study or the Diabetes Control and Complications Trial (DCCT). GFR was measured as the renal clearance of (I-125)iothalamate after an sc injection without epinephrine. The studies used similar protocols for obtaining blood and urine, training clinical center staff, and processing specimens in central laboratories. The performance of GFR measurements, assessed from adherence to protocol and quality control analyses, was excellent. The variability among the four clearance periods (intratest coefficient of variation (CV)) was acceptable; the median intratest CV for GFR was 9.4% in the MDRD Study and 11.7% in the DCCT. The pattern of decline in serum counts was better approximated by an exponential rather than a linear relationship. The cause of the intratest variability in GFR measurements was explored by univariate and multivariate analysis. The intratest CV was highest at the extremes of GFR. Among patients with a high GFR (>90 mL/min per 1.73 m2), most of whom were participants in the DCCT, the higher intratest GFR was due, in part, to a systematic decline in GFR during the test. Among patients with a very low GFR (<13 mL/min per 1.73 m2), technical difficulties in urine collections contributed substantially to the higher intratest CV. Other patient characteristics, including age, gender, weight, serum glucose, renal diagnosis, and use of diuretics, were not strongly correlated with the intratest CV. The precision of GFR measurements was assessed from the variability from measurement to measurement (intertest CV). Among MDRD Study subjects, in whom two measurements of GFR were performed over a 3-month interval, the median intertest CV was relatively low (6.3%) and was only weakly related to the intratest CV. Thus, GFR measurements are reasonably precise, even if the intratest CV is high. Given the relatively high intratest CV that is characteristic of GFR measurements, the estimate of GFR in an individual is more precise if multiple clearance periods, rather than a single period, are included. Similarly, the estimate of mean GFR for a population is also more precise if multiple clearance periods are included. In conclusion, by the use of standardized methods, an acceptable precision of GFR results can be obtained in multicenter trials. The same methods can be applied in clinical practice. The usefulness of GFR measurements in practice depends, in part, on the results of these and other ongoing clinical trials investigating therapeutic interventions to prevent the onset or retard the progression of renal disease. C1 NIDDKD, BETHESDA, MD USA. FU NIDDK NIH HHS [N01 DK062204-A, N01 DK062204] NR 31 TC 163 Z9 168 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 1993 VL 4 IS 5 BP 1159 EP 1171 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA MJ998 UT WOS:A1993MJ99800009 PM 8305642 ER PT J AU GREENE, T BOURGOIGNIE, JJ HABWE, V KUSEK, JW SNETSELAAR, LG SOUCIE, JM YAMAMOTO, ME AF GREENE, T BOURGOIGNIE, JJ HABWE, V KUSEK, JW SNETSELAAR, LG SOUCIE, JM YAMAMOTO, ME TI BASE-LINE CHARACTERISTICS IN THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY (VOL 3, PG 1819, 1993) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Correction, Addition DE PROTEIN; BLOOD PRESSURE; GFR; CLINICAL TRIAL; KIDNEY DISEASE ID PROTEIN RESTRICTION; CLINICAL-TRIALS; INSUFFICIENCY; PROGRESSION; FAILURE; METAANALYSIS AB The Modification of Diet in Renal Disease Study is randomized, multicenter, clinical trial designed to determine the effects of three levels of dietary control of protein and phosphorus and two levels of blood pressure control on the rate of decline of kidney function among persons with chronic renal disease. Study participants were assigned to one of two studies, Study A or Study B, depending on their GFR just before randomization. Within each study, participants were randomly allocated to one of two levels of blood pressure control and to one of two dietary interventions according to separate 2 x 2 factorial designs. A total of 840 men and women aged 18 to 70 were randomized. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized participants at the time of entry into the trial, overviews the protocol and purposes of the baseline period before randomization, and evaluates the balance among the treatment intervention groups within Studies A and B at the time of randomization. Major indicators of renal function were found to be well balanced among the treatment groups. Selected baseline characteristics of participants in the Modification of Diet in Renal Disease Study are compared with those of other renal clinical trials and with those of new cases of treated ESRD reported in the United States Renal Data System. C1 UNIV MIAMI,SCH MED,MIAMI,FL 33152. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. NIH,BETHESDA,MD 20892. EMORY UNIV,ATLANTA,GA 30322. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. RP GREENE, T (reprint author), CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 32 TC 30 Z9 30 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 1993 VL 4 IS 5 BP 1221 EP 1236 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA MJ998 UT WOS:A1993MJ99800019 PM 8305650 ER PT J AU ZACHARY, AA AF ZACHARY, AA TI IS THERE RACIAL BIAS IN TRANSPLANTATION SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material RP ZACHARY, AA (reprint author), NIAID,TRANSPLANTAT SECT,SOLAR BLDG,RM 4A13,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 1993 VL 85 IS 11 BP 821 EP 823 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA MG698 UT WOS:A1993MG69800001 PM 8107155 ER PT J AU MATTHEW, E NORDAHL, T SCHUT, L KING, AC COHEN, R AF MATTHEW, E NORDAHL, T SCHUT, L KING, AC COHEN, R TI METABOLIC AND COGNITIVE CHANGES IN HEREDITARY ATAXIA SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE HEREDITARY ATAXIA; CEREBRAL GLUCOSE METABOLISM; CEREBELLUM; FRONTAL CORTEX; [F-18]-2-FLUORO-2-DEOXY-D-GLUCOSE; POSITRON EMISSION TOMOGRAPHY ID INHERITED OLIVOPONTOCEREBELLAR ATROPHY; POSITRON EMISSION TOMOGRAPHY; CHOLINERGIC HYPOTHESIS; SPINOCEREBELLAR ATAXIA; GLUCOSE-UTILIZATION; ALZHEIMER-TYPE; CEREBELLAR; REDUCTION; MEMORY; LOCALIZATION AB Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were studied with [F-18]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance imaging (MRI), cognitive testing and scored neurological examination, and compared with normal controls. The neurological examination, MRI and cognitive tests showed no significant differences between at risk and normal control subjects. Mild cognitive deficits were seen in affected subjects; the degree of cognitive change appeared to relate to the severity of the illness. MRI demonstrated cerebellar and brainstem atrophy in all affected subjects. PET studies showed higher global metabolic rates (mean [SD]) in at risk subjects (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g). Normalized (region/global average) regional metabolic rates were reduced in cerebellar hemispheres and vermis, and in frontal and prefrontal areas of affected subjects in comparison to at risk and normal control subjects. These findings indicate that functional changes in some forms of autosomal dominant hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to involve other parts of the neuraxis. C1 NIMH,CEREBRAL BLOOD FLOW & METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT NEUROL,MINNEAPOLIS,MN 55455. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 40 TC 19 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV PY 1993 VL 119 IS 2 BP 134 EP 140 DI 10.1016/0022-510X(93)90125-I PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ME915 UT WOS:A1993ME91500002 PM 8277326 ER PT J AU TREADWELL, MC SEPULVEDA, W LEBLANC, LL ROMERO, R AF TREADWELL, MC SEPULVEDA, W LEBLANC, LL ROMERO, R TI PRENATAL-DIAGNOSIS OF FETAL CUTANEOUS HEMANGIOMA - CASE-REPORT AND REVIEW OF THE LITERATURE SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review ID CONGESTIVE HEART-FAILURE; CAVERNOUS HEMANGIOMA; DOPPLER VELOCIMETRY; GIANT HEMANGIOMA; SONOGRAPHIC DIAGNOSIS; NEWBORN; INFANT; MASS C1 NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP TREADWELL, MC (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 19 TC 17 Z9 18 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 1993 VL 12 IS 11 BP 683 EP 687 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA ME260 UT WOS:A1993ME26000017 PM 8264023 ER PT J AU ALEXANDER, RB LINEHAN, WM AF ALEXANDER, RB LINEHAN, WM TI INTERFERON-ALPHA PRIMED TUMOR-INFILTRATING LYMPHOCYTES COMBINED WITH INTERLEUKIN-2 AND INTERFERON-ALPHA AS THERAPY FOR METASTATIC RENAL-CELL CARCINOMA - COMMENT SO JOURNAL OF UROLOGY LA English DT Letter RP ALEXANDER, RB (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1993 VL 150 IS 5 BP 1390 EP 1390 PN 1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA MC576 UT WOS:A1993MC57600011 ER PT J AU HILFENHAUS, S COHEN, BJ BATES, C KAJIGAYA, S YOUNG, NS ZAMBON, M MORTIMER, PP AF HILFENHAUS, S COHEN, BJ BATES, C KAJIGAYA, S YOUNG, NS ZAMBON, M MORTIMER, PP TI ANTIBODY-CAPTURE HAEMADHERENCE TESTS FOR PARVOVIRUS B19-SPECIFIC IGM AND IGG SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE PARVOVIRUS B19; HAEMADHERENCE; IGM; IGG ID HEMAGGLUTINATION; ASSAY; B19 AB In the absence of serum inhibitor human parvovirus B19 agglutinates primate red cells. Agglutination of baboon erythrocytes by inhibitor free baculovirus expressed VP1/VP2 proteins of B19 virus was enhanced by low pH. To avoid interference from inhibitor(s) present in serum specimens microtitre tests with an antibody capture configuration were designed and optimised. Antigen binding was demonstrated by the adherence of baboon erythrocytes. These tests (MACHAT, GACHAT) detected IgM or IgG anti-B19 in 1032 serum specimens with an overall sensitivity of 99%, specificity of 98.2% and positive predictive value of 96.8% with reference to the radioimmunoassays currently in diagnostic use. MACHAT and GACHAT are straightforward, and well suited to large scale research and seroepidemiological investigations. They are without the risks from infectious antigen and radiation associated with existing radioimmunoassays and allow the phenomenon of B19 virus haemagglutination to be put to practical advantage. C1 CENT PUBL HLTH LAB,DIV VIRUS REFERENCE,61 COLINDALE AVE,LONDON NW9 5HT,ENGLAND. ST MARYS HOSP,LONDON W2 1NY,ENGLAND. NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 1993 VL 45 IS 1 BP 27 EP 37 DI 10.1016/0166-0934(93)90137-G PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA MF521 UT WOS:A1993MF52100003 PM 8270653 ER PT J AU PURCELL, DFJ MARTIN, MA AF PURCELL, DFJ MARTIN, MA TI ALTERNATIVE SPLICING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNA MODULATES VIRAL PROTEIN EXPRESSION, REPLICATION, AND INFECTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID REV GENE-PRODUCT; TARGET SEQUENCE; FUNCTIONAL-ANALYSIS; FUSION PROTEIN; HIV-1 REV; ENV; TAT; REGION; INVITRO; AIDS AB Multiple RNA splicing sites exist within human immunodeficiency virus type 1 (HIV-1) genomic RNA, and these sites enable the synthesis of many mRNAs for each of several viral proteins. We evaluated the biological significance of the alternatively spliced mRNA species during productive HIV-1 infections of peripheral blood lymphocytes and human T-cell lines to determine the potential role of alternative RNA splicing in the regulation of HIV-1 replication and infection. First, we used a semiquantitative polymerase chain reaction of cDNAs that were radiolabeled for gel analysis to determine the relative abundance of the diverse array of alternatively spliced HIV-1 mRNAs. The predominant rev, tat, vpr, and env RNAs contained a minimum of noncoding sequence, but the predominant nef mRNAs were incompletely spliced and invariably included noncoding exons. Second, the effect of altered RNA processing was measured following mutagenesis of the major 5' splice donor and several cryptic, constitutive, and competing 3' splice acceptor motifs of HIV-1NL4-3. Mutations that ablated constitutive splice sites led to the activation of new cryptic sites; some of these preserved biological function. Mutations that ablated competing splice acceptor sites caused marked alterations in the pool of virus-derived mRNAs and, in some instances, in virus infectivity and/or the profile of virus proteins. The redundant RNA splicing signals in the HIV-1 genome and alternatively spliced mRNAs provides a mechanism for regulating the relative proportions of HIV-1 proteins and, in some cases, viral infectivity. RP PURCELL, DFJ (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. RI Purcell, Damian/G-5068-2011 NR 60 TC 290 Z9 290 U1 1 U2 4 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 NOV PY 1993 VL 67 IS 11 BP 6365 EP 6378 PG 14 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600004 PM 8411338 ER PT J AU OBERSTE, MS WILLIAMSON, JC GREENWOOD, JD NAGASHIMA, K COPELAND, TD GONDA, MA AF OBERSTE, MS WILLIAMSON, JC GREENWOOD, JD NAGASHIMA, K COPELAND, TD GONDA, MA TI CHARACTERIZATION OF BOVINE IMMUNODEFICIENCY VIRUS REV CDNAS AND IDENTIFICATION AND SUBCELLULAR-LOCALIZATION OF THE REV PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID BIOLOGICALLY-ACTIVE PROVIRUSES; GENE-PRODUCT; VISNA VIRUS; HIV-1 REV; RECOMBINANT BACULOVIRUS; MOLECULAR-CLONING; EDITING PROGRAM; TRANS-ACTIVATOR; ENV EXPRESSION; MESSENGER-RNA AB One of the six putative accessory genes of bovine immunodeficiency virus (BIV) is similar to those identified as rev in the human immunodeficiency virus and visna virus genomes. To further analyze the BIV rev gene locus, protein, and function, rev cDNAs were cloned and characterized. BIV rev mRNA is derived from the full-length transcript by multiple splicing events and consists of three exons, including the untranslated leader sequence and two coding exons. BIV rev cDNA was expressed in bacteria and in a mammalian in vitro translation expression system. A 23-kDa Rev protein (p23rev) was immunologically detected in lysates from both systems by using an antiserum made to a synthetic Rev peptide. Recombinant p23rev made in bacteria was purified and used to make a polyvalent antiserum. Antisera to Rev peptide and recombinant p23rev immunoprecipitated p23rev from BIV-infected mammalian cells but not from virions. A mammalian expression vector using the BIV rev cDNA was constructed; p23rev was immunoprecipitated with anti-Rev serum from P-32-labeled lysates of monkey cells transfected with this plasmid, demonstrating that BIV Rev is phosphorylated. Immunofluorescence and immunoelectron microscopy with anti-BIV Rev antisera localized Rev in the nucleus and, particularly, in the nucleoli of BIV-infected cells. In functional studies, the expression of BIV Rev was shown to positively regulate the appearance both of Gag protein, which is translated from the unspliced primary viral transcript, and of singly spliced env mRNA but not that of the multiply spliced tat mRNA. These results demonstrate that BIV Rev activity correlates with the known function of lentivirus Rev proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 57 TC 31 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1993 VL 67 IS 11 BP 6395 EP 6405 PG 11 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600007 PM 8411341 ER PT J AU GOLDING, H BLUMENTHAL, R MANISCHEWITZ, J LITTMAN, DR DIMITROV, DS AF GOLDING, H BLUMENTHAL, R MANISCHEWITZ, J LITTMAN, DR DIMITROV, DS TI CELL-FUSION MEDIATED BY INTERACTION OF A HYBRID CD4.CD8 MOLECULE WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN DOES OCCUR AFTER A LONG LAG TIME SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; HTLV-III/LAV ENVELOPE; CD4+ CELLS; MONOCLONAL-ANTIBODIES; CD4-MEDIATED FUSION; SYNCYTIUM FORMATION; MEMBRANE-FUSION; INITIAL-STAGES; INFECTION; HIV AB Several domains of CD4 have been suggested to play a critical role in events that follow its binding to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41). It has been reported previously that cells expressing a chimeric molecule consisting of the first 177 residues of human CD4 attached to residues from the hinge, transmembrane, and cytoplasmic domains of human CD8 did not form syncytia with HIV-1-infected cells (L. Poulin, L. A. Evans, S. Tang, A. Barboza, H. Legg, D. R. Littman, and J. A. Levy, J. Virol. 65:4893-4901, 1991). In contrast, we found that the hybrid CD4.CD8 molecule expressed in human cells did render them susceptible to fusion with cells expressing HIV-1IIIB or HIV-1RF envelope glycoproteins encoded by vaccinia virus recombinants, but only after long lag times. The lag time of membrane fusion mediated by the hybrid CD4.CD8 molecule was fivefold longer than that for the wild-type CD4 molecule. However, the rate of binding to and the affinity of soluble gp120 for membrane-associated CD4.CD8 were the same as for CD4. Both molecules were laterally mobile, as determined by patching experiments. Coexpression of the CD4.CD8 chimera with wild-type CD4 did not lead to interference in fusion but had an additive effect. Therefore, the proximal membrane domains of CD4 play an important role in determining the kinetics of postbinding events leading to membrane fusion. We hypothesize that the long lag time is due to the inability of the CD4.CD8-gp120-gp41 complex to undergo the rapid conformational changes which occur during the fusion mediated by wild-type CD4. C1 NCI, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. US FDA, DIV VIROL, BETHESDA, MD 20892 USA. UNIV CALIF SAN FRANCISCO, SCH MED, HOWARD HUGHES MED INST, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA. NR 38 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1993 VL 67 IS 11 BP 6469 EP 6475 PG 7 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600016 PM 8411350 ER PT J AU KAWANO, H ROSTAPSHOV, V ROSEN, L LAI, CJ AF KAWANO, H ROSTAPSHOV, V ROSEN, L LAI, CJ TI GENETIC-DETERMINANTS OF DENGUE TYPE-4 VIRUS NEUROVIRULENCE FOR MICE SO JOURNAL OF VIROLOGY LA English DT Article ID PARTIAL NUCLEOTIDE-SEQUENCE; NONSTRUCTURAL PROTEIN NS1; AMINO-ACID SEQUENCES; NEW-GUINEA-C; STRUCTURAL PROTEINS; ENCEPHALITIS; GENOME; RNA; CONSTRUCTION; STRAINS AB Mouse-adapted dengue type 4 virus (DEN4) strain H241 is highly neurovirulent for mice, whereas its non-mouse-adapted parent is rarely neurovirulent. The genetic basis for the neurovirulence of the mouse-adapted adapted mutant was studied by comparing intratypic chimeric viruses that contained the three structural protein genes from the parental virus or the neurovirulent mutant in the background sequence of nonneurovirulent DEN4 strain 814669. The chimera that contained the three structural protein genes from mouse neurovirulent DEN4 strain H241 proved to be highly neurovirulent in mice, whereas the chimera that contained the corresponding genes from its non-mouse-adapted parent was not neurovirulent. This finding indicates that most of the genetic loci for the neurovirulence of the DEN4 mutant lie within the structural protein genes. A comparison of the amino acid sequences of the parent and its mouse neurovirulent mutant proteins revealed that there were only five amino acid differences in the structural protein region, and three of these were located in the envelope (E) glycoprotein. Analysis of chimeras which contained one or two of the variant amino acids of the mutant E sequence substituting for the corresponding sequence of the parental virus identified two of these amino acid changes as important determinants of mouse neurovirulence. First, the single substitution of Ile for Thr-155 which ablated one of the two conserved glycosylation sites in parental E yielded a virus that was almost as neurovirulent as the mouse-adapted mutant. Thus, the loss of an E glycosylation site appears to play a role in DEN4 neurovirulence. Second, the substitution of Leu for Phe-401 also yielded a neurovirulent virus, but it was less neurovirulent than the glycosylation mutant. These findings indicate that at least two of the genetic loci responsible for DEN4 mouse neurovirulence map within the structural protein genes. C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. UNIV HAWAII,PACIFIC BIOMED RES CTR,ARBOVIRUS PROGRAM,HONOLULU,HI 96822. NR 33 TC 82 Z9 91 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 NOV PY 1993 VL 67 IS 11 BP 6567 EP 6575 PG 9 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600027 PM 8411360 ER PT J AU CARVALHO, M KIRKLAND, M DERSE, D AF CARVALHO, M KIRKLAND, M DERSE, D TI PROTEIN INTERACTIONS WITH DNA ELEMENTS IN VARIANT EQUINE INFECTIOUS-ANEMIA VIRUS ENHANCERS AND THEIR IMPACT ON TRANSCRIPTIONAL ACTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; CHLORAMPHENICOL ACETYLTRANSFERASE; PERSISTENT INFECTION; MURINE RETROVIRUSES; PROCESSIVITY FACTOR; GENE-EXPRESSION; TAT; TISSUE; HIV-1; LOCALIZATION AB The long terminal repeats (LTRs) from various cloned equine infectious anemia virus (EIAV) proviruses differ significantly, but all contain cis-acting DNA elements identical to MDBP-, PEA2-, AP-1-, and PU.1(ets)-binding sites. A prototype EIAV LTR would contain one of each of these conserved elements. The LTR variations originate from the insertion of novel sequences between the PEA2 and AP-1 elements in the transcriptional enhancer unit. Viewed in this way, the LTR from provirus clone lambda12 has an 11-bp insertion containing a PEA2 site and the LTR of the lambda6 provirus has a 31-bp insertion/duplication containing PEA2, AP-1, and PU.1 sites. Two other LTRs were cloned by amplification of cDNAs from the persistently infected cell line, EIAV-FEA. A third LTR was generated by site-directed mutagenesis of one of the LTRs from EIAV-FEA cells. The latter three had a single base change in the element next to the TATA box that abolished PU.1 binding; however, the variable regions of these LTRs were shown by gel mobility shift assays to contain one or two PU.1 sites. One variable region was shown to have an octamer site overlapping its tandem PU.1 elements. Basal, PMA-activated, and Tat trans-activated transcriptional activities of the LTRs were compared in several different cell lines by transient transfection. The various promoters displayed different relative levels of activity depending on the cell line used and the condition of activation. This natural set of variant promoters may help define how changes in the components of the transcription complex influence transactivation by Tat. The diverse LTRs could endow their respective proviruses with a unique pattern of expression and activation in vivo. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 33 TC 25 Z9 26 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1993 VL 67 IS 11 BP 6586 EP 6595 PG 10 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600029 PM 8411361 ER PT J AU LI, G LISZIEWICZ, J SUN, D ZON, G DAEFLER, S WONGSTAAL, F GALLO, RC KLOTMAN, ME AF LI, G LISZIEWICZ, J SUN, D ZON, G DAEFLER, S WONGSTAAL, F GALLO, RC KLOTMAN, ME TI INHIBITION OF REV ACTIVITY AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION BY ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE ANALOGS DIRECTED AGAINST THE REV-RESPONSIVE ELEMENT SO JOURNAL OF VIROLOGY LA English DT Note ID VIRAL MESSENGER-RNA; ACETYLTRANSFERASE GENE-EXPRESSION; CHRONICALLY INFECTED-CELLS; RETROVIRUSES HTLV-III; HIV-1 REV; TARGET SEQUENCE; TRANS-ACTIVATOR; SECONDARY STRUCTURE; VIRION EXPRESSION; REGULATORY GENES AB The interaction between the Rev protein of human immunodeficiency virus type 1 and its highly structured and conserved RNA target, the Rev-responsive element, is required for virus replication. We demonstrate that antisense oligodeoxynucleotide phosphorothioate analogs directed against the Rev-responsive element effectively inhibit Rev activity, as well as human immunodeficiency virus type 1 replication, and are candidates for antiviral therapy. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LYNX THERAPEUT INC,FOSTER CITY,CA 94404. NYU MED CTR,DEPT MED,NEW YORK,NY 10016. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. RI klotman, mary/A-1921-2016 NR 73 TC 30 Z9 30 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 NOV PY 1993 VL 67 IS 11 BP 6882 EP 6888 PG 7 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600070 PM 8411393 ER PT J AU BACK, NKT SMIT, L SCHUTTEN, M NARA, PL TERSMETTE, M GOUDSMIT, J AF BACK, NKT SMIT, L SCHUTTEN, M NARA, PL TERSMETTE, M GOUDSMIT, J TI MUTATIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP41 AFFECT SENSITIVITY TO NEUTRALIZATION BY GP120 ANTIBODIES SO JOURNAL OF VIROLOGY LA English DT Note ID MONOCLONAL-ANTIBODIES; ANTIPEPTIDE ANTIBODIES; POINT MUTATION; V3 LOOP; HIV-1; ENVELOPE; IDENTIFICATION; INFECTION; DOMAIN; SERA AB Three closely related molecular human immunodeficiency virus type 1 (HIV-1) clones, with differential neutralization phenotypes, were generated by cloning of an NcoI-BamHI envelope (env) gene fragment (HXB2R nucleotide positions 5221 to 8021) into the full-length HXB2 molecular clone of HIV-1 IIIB. These env gene fragments, containing the complete gp120 coding region and a major part of gp41, were obtained from three different biological clones derived from a chimpanzee-passaged HIV-1 IIIB isolate. Two of the viruses thus obtained (4.4 and 5.1) were strongly resistant to neutralization by infection-induced chimpanzee and human polyclonal antibodies and by HIV-1 IIIB V3-specific monoclonal antibodies and weakly resistant to soluble CD4 and a CD4-binding-site-specific monoclonal antibody. The third virus (6.8) was sensitive to neutralization by the same reagents. The V3 coding sequence and the gp120 amino acid residues important for the discontinuous neutralization epitope overlapping the CD4-binding site were completely conserved among the clones. However, the neutralization-resistant clones 4.4 and 5.1 differed from neutralization-sensitive clone 6.8 by two mutations in gp41. Exchange experiments confirmed that the 3' end of clone 6.8 (nucleotides 6806 to 8021; amino acids 346 to 752) conferred a neutralization-sensitive phenotype to both of the neutralization-resistant clones 4.4 and 5.1. From our study, we conclude that mutations in the extracellular portion of gp41 may affect neutralization sensitivity to gp120 antibodies. C1 NATL INST PUBL HLTH & ENVIRONM PROTECT,IMMUNOBIOL LAB,3720 BA BILTHOVEN,NETHERLANDS. NCI,FREDERICK CANC RES & DEV CTR,TUMOR CELL BIOL LAB,FREDERICK,MD 21701. RP BACK, NKT (reprint author), UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,1105 AZ AMSTERDAM,NETHERLANDS. RI Back, Nicole/K-3884-2013 NR 37 TC 52 Z9 54 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 NOV PY 1993 VL 67 IS 11 BP 6897 EP 6902 PG 6 WC Virology SC Virology GA MC016 UT WOS:A1993MC01600073 PM 8411395 ER PT J AU ROTH, GS BRENNECKE, LH FRENCH, AW WILLIAMS, NG WAGGIE, KS SPURGEON, HA INGRAM, DK AF ROTH, GS BRENNECKE, LH FRENCH, AW WILLIAMS, NG WAGGIE, KS SPURGEON, HA INGRAM, DK TI PATHOLOGICAL CHARACTERIZATION OF MALE WISTAR RATS FROM THE GERONTOLOGY RESEARCH-CENTER SO JOURNALS OF GERONTOLOGY LA English DT Article ID LIFE-SPAN; RESTRICTION; AGE; HYDRONEPHROSIS; MODULATION; GROWTH AB Male Wistar rats aged 6-26 months were obtained from the colony of The Gerontology Research Center of the National Institute on Aging, and pathological profiles were assessed. One hundred animals were sacrificed at 6, 12, 18, 21, 24, and 26 months and used for cross-sectional determinations; also, 150 animals were followed longitudinally and sacrificed when clinical signs of moribundity appeared. Renal disease contributed the most common pathology observed in both studies (found in over 70% of the animals examined), with neoplasms a secondary problem (pituitary tumors were by far the most prevalent, with adenomas present in almost-equal-to 20% of the animals). This analysis represents the first complete pathological characterization of this commonly used rat model for aging research, and offers an opportunity for comparison with other rat strains. C1 NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT COMPARAT MED,BALTIMORE,MD 21205. NR 46 TC 18 Z9 18 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 NOV PY 1993 VL 48 IS 6 BP B213 EP B230 PG 18 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA MH025 UT WOS:A1993MH02500003 PM 8227989 ER PT J AU RAY, PE MCCUNE, BK GOMEZ, RA HORIKOSHI, S KOPP, JB KLOTMAN, PE AF RAY, PE MCCUNE, BK GOMEZ, RA HORIKOSHI, S KOPP, JB KLOTMAN, PE TI RENAL VASCULAR INDUCTION OF TGF-BETA-2 AND RENIN BY POTASSIUM-DEPLETION SO KIDNEY INTERNATIONAL LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; SMOOTH-MUSCLE CELLS; ANGIOTENSINOGEN GENE-EXPRESSION; FACTOR TGF-BETA; RAT-KIDNEY; PROLIFERATION; SECRETION; HYPERPLASIA; HYPERTROPHY; INHIBITION AB Recently, we have found that transforming growth factor (TGF)-beta2 and renin are abundantly expressed in the juxtaglomerular apparatus (JGA) of dehydrated mice. Since potassium (K+) depletion also stimulates renin and induces hypertrophy of the JGA, we examined the ability of this maneuver to stimulate TGF-beta isoforms and renin in renovascular tissue and the JGA of young rats. Sprague-Dawley rats (50 +/- 5 g) were fed either a control diet or a potassium-deficient diet (< 0.05% K) for 7, 16, or 21 days. As a control for TGF-beta and renin stimulation, an additional group of animals was fed a normal diet but was water deprived for three days. Potassium-depleted animals experienced severe growth retardation but kidney weight increased significantly. Potassium depletion induced both TGF-beta2 and renin immunoreactivity in renal arterioles and the JGA but had no effect on TGF-beta1 and TGF-beta3 isoforms. To determine the role of circulating angiotensin II in the stimulation of TGF-beta2 by potassium depletion, a group of potassium-depleted rats received enalapril (100 mg/liter) in the drinking water. The addition of converting enzyme inhibitor increased both the intensity of TGF-beta2 and renin staining as well as the number of cells positively stained. Our results demonstrate that K+ depletion induces TGF-beta2 and renin in renal arterioles and in the JGA. Furthermore, circulating angiotensin II is not responsible for the increase in the local expression of TGF-beta2. These findings suggest that TGF-beta2 may be an important mediator of JGA hypertrophy. The simultaneous induction of TGF-beta2 with renin suggests that these factors may be coregulated. C1 UNIV VIRGINIA,MED CTR,SCH MED,DEPT NEPHROL,CHARLOTTESVILLE,VA 22901. CHILDRENS NATL MED CTR,CHILDRENS RES INST,WASHINGTON,DC. JOHNS HOPKINS & FRANCIS SCOTT KEY MED CTR,DEPT PATHOL,BALTIMORE,MD. RP RAY, PE (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 1993 VL 44 IS 5 BP 1006 EP 1013 DI 10.1038/ki.1993.342 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA MB448 UT WOS:A1993MB44800010 PM 7505348 ER PT J AU CRAIG, SS IRANI, AMA METCALFE, DD SCHWARTZ, LB AF CRAIG, SS IRANI, AMA METCALFE, DD SCHWARTZ, LB TI ULTRASTRUCTURAL-LOCALIZATION OF HEPARIN TO HUMAN MAST-CELLS OF THE MC(TC) AND MC(T) TYPES BY LABELING WITH ANTITHROMBIN III-GOLD SO LABORATORY INVESTIGATION LA English DT Article DE CHONDROITIN SULFATE-E; TRYPTASE; CHYMASE; MAST CELL SUBSETS ID CHONDROITIN SULFATE-E; MOUSE BONE-MARROW; HUMAN-LUNG; CONNECTIVE-TISSUE; OVERSULFATED CHONDROITIN; CYTO-CHEMISTRY; E PROTEOGLYCAN; IDENTIFICATION; RAT; COMPLEXES AB BACKGROUND: Mast cells derived from human skin and lung have been reported to produce heparin and chondroitin sulfate E proteoglycans. However, no information about the proteoglycans distribution among the different human mast cell types (MC(TC) and MC(T)) is available. Conjugates of antithrombin III-gold were used to assess the presence of heparin in both human mast cell subsets. EXPERIMENTAL DESIGN: Thin sections of human and rodent tissues and dispersed cell preparations were labeled with the conjugate in the presence of saline, heparin, and chondroitin sulfates A and E and particle densities were measured over granules, perigranular regions, and extracellular space. Control sections were preincubated with heparinase, chondroitinase ABC, or buffer. RESULTS: Labeling with antithrombin III-gold particles was detected in essentially all granules of human mast cells in skin (predominantly MC(TC) type), lung alveolar wall, and bowel mucosa (predominantly MC(T) type), but was negligible over human eosinophils. Consistent with the known distribution of heparin in rodent mast cells, strong labeling was observed over rat peritoneal connective tissue type mast cells, but not over mucosal mast cells in bowel mucosa of Nippostrongylus brasiliensis-infected rats (which contain chondroitin sulfate di-B) nor over mouse PT-18 mast cells (which contain chondroitin sulfate E). Mast cell labeling was preferentially blocked by exogenous heparin, and virtually abolished by heparinase but not chondroitinase ABC preincubation. CONCLUSIONS: The data with rodent mast cells indicate that antithrombin III-gold labels cells that contain heparin, but not those that contain only over-sulfated chondroitin sulfates. Specificity of the procedure for detecting heparin is further demonstrated by inhibition of labeling after preincubation with heparinase and by competition with exogenous heparin. On this basis, we conclude that heparin is present in essentially all mast cells in normal skin, lung alveolar wall, and bowel mucosa. The presence of heparin in all human mast cells is different than for rodent mast cells, and probably accounts for the inability to clearly distinguish different human mast cell types from one another with histochemical stains based on proteoglycan content. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT INTERNAL MED,RICHMOND,VA 23298. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP CRAIG, SS (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT ANAT,BOX 709 MCV STN,RICHMOND,VA 23298, USA. FU NIAID NIH HHS [AI-27517, AI-20487] NR 54 TC 35 Z9 35 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1993 VL 69 IS 5 BP 552 EP 561 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA MK486 UT WOS:A1993MK48600007 PM 8246447 ER PT J AU SCHREURS, BG KEHOE, EJ GORMEZANO, I AF SCHREURS, BG KEHOE, EJ GORMEZANO, I TI CONCURRENT ASSOCIATIVE TRANSFER AND COMPETITION IN SERIAL CONDITIONING OF THE RABBITS NICTITATING-MEMBRANE RESPONSE SO LEARNING AND MOTIVATION LA English DT Article ID CS-US CONTIGUITY; COMPOUND STIMULI; BLOCKING; CONFIGURATION; INTENSITY; SUMMATION C1 UNIV IOWA,DEPT PSYCHOL,IOWA CITY,IA 52242. NIH,BETHESDA,MD 20892. UNIV NEW S WALES,KENSINGTON,NSW 2033,AUSTRALIA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 44 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0023-9690 J9 LEARN MOTIV JI Learn. Motiv. PD NOV PY 1993 VL 24 IS 4 BP 395 EP 412 DI 10.1006/lmot.1993.1022 PG 18 WC Psychology, Biological; Psychology, Experimental SC Psychology GA MF358 UT WOS:A1993MF35800003 ER PT J AU WANG, J RAFFELD, M MEDEIROS, LJ LONGO, DL JAFFE, ES DUFFEY, P STETLERSTEVENSON, M AF WANG, J RAFFELD, M MEDEIROS, LJ LONGO, DL JAFFE, ES DUFFEY, P STETLERSTEVENSON, M TI FOLLICULAR CENTER CELL LYMPHOMA WITH THE T(14 18) TRANSLOCATION IN WHICH THE REARRANGED BCL-2 GENE IS SILENT SO LEUKEMIA LA English DT Article ID NEOPLASTIC-CELLS; HYPERPLASIA; EXPRESSION; DISEASE AB Using reverse transcription and the polymerase chain reaction (RT-PCR), we determined the level of expression of BCL-2/IgH in 18 follicular center cell lymphomas containing a t(14;18) translocation involving the major breakpoint region and five non-neoplastic lymph nodes. BCL-2/IgH transcripts were demonstrated in 16 follicular center cell lymphoma cases (five high, 11 low) and were not present in any of the five non-neoplastic lymph nodes. In the two follicular lymphoma cases in which BCL-2/IgH transcripts could not be detected by RT-PCR, PCR amplification of genomic DNA indicated this was not due to primer selection. In addition, non-expression was confirmed at the protein level by immunoperoxidase studies. We therefore conclude that these represent true negative cases. This is the first time primary follicular lymphoma cases have been quantitatively studied at the RNA level for expression of BCL-2. We conclude that RT-PCR is a sensitive method for determining levels of expression of this oncogene and may be useful in studying the involvement of BCL-2 in follicular lymphoma. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 18 TC 16 Z9 16 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1993 VL 7 IS 11 BP 1834 EP 1839 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA MJ971 UT WOS:A1993MJ97100018 PM 7694006 ER PT J AU ORGAMBIDE, GG HUANG, ZH GAGE, DA DAZZO, FB AF ORGAMBIDE, GG HUANG, ZH GAGE, DA DAZZO, FB TI PHOSPHOLIPID AND FATTY-ACID COMPOSITIONS OF RHIZOBIUM-LEGUMINOSARUM BIOVAR TRIFOLII ANU843 IN RELATION TO FLAVONE-ACTIVATED PSYM NOD GENE-EXPRESSION SO LIPIDS LA English DT Article ID NODULATION; MELILOTI AB The phospholipid and associated fatty acid compositions of the bacterial symbiont of clover, Rhizobium leguminosarum biovar trifolii wild-type ANU843, was analyzed by two-dimensional silica thin-layer chromatography, fast atom bombardment-mass spectrometry, flame-ionization detection gas-liquid chromatography and combined gas-liquid chromatography/mass spectrometry. The phospholipid composition included phosphatidylethanolamine (15%), N-methylphosphatidylethanolamine (47%), N,N-dimethylphosphatidylethanolamine (9%), phosphatidylglycerol(19%), cardiolipin (5%) and phosphatidylcholine (2%). Fatty acid composition included predominantly cis-11-octadecenoic acid, lower levels of cis-9-hexadecenoic acid, hexadecanoic acid, 11-methyl-11-octadecenoic acid, octadecanoic acid, 11,12-methyleneoctadecanoic acid, eicosanoic acid and traces of branched, and di- and triunsaturated fatty acids. The influence of expression of the ''nodulation'' genes encoding symbiotic functions on the composition of these membrane lipids was examined in wild;type cells grown with or without the flavone inducer, 4',7-dihydroxyflavone and in mutated cells lacking the entire symbiotic plasmid where these genes reside, or containing single transposon insertions in selected nodulation genes. No significant changes in phospholipid or associated fatty acid compositions were detected by the above methods of analysis. C1 MICHIGAN STATE UNIV,DEPT MICROBIOL,E LANSING,MI 48824. MICHIGAN STATE UNIV,NIH,DEPT BIOCHEM,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. FU NCRR NIH HHS [RR00480] NR 21 TC 19 Z9 19 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD NOV PY 1993 VL 28 IS 11 BP 975 EP 979 DI 10.1007/BF02537117 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA MF949 UT WOS:A1993MF94900003 PM 8277828 ER PT J AU VANZIJL, PCM CHESNICK, AS DESPRES, D MOONEN, CTW RUIZCABELLO, J VANGELDEREN, P AF VANZIJL, PCM CHESNICK, AS DESPRES, D MOONEN, CTW RUIZCABELLO, J VANGELDEREN, P TI IN-VIVO PROTON SPECTROSCOPY AND SPECTROSCOPIC IMAGING OF (1-C-13)-GLUCOSE AND ITS METABOLIC PRODUCTS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE C-13-GLUCOSE METABOLISM; PROTON SPECTROSCOPY; SPECTROSCOPIC IMAGING; 2D SPECTROSCOPY ID PULSED FIELD GRADIENTS; C-13 NMR-SPECTROSCOPY; RAT-BRAIN INVIVO; QUADRATURE DETECTION; GLUCOSE; HMQC; <1-C-13>GLUCOSE; GLUTAMATE; COSY AB Metabolism of {1-C-13}-glucose was studied in situ in cat brain using gradient-enhanced proton-detected heteronuclear spectroscopy. Proton detection of {1-C-18}-glucose, {3-C-13}-lactate, 4-{C-13}-glutamine, 4-{C-13}-glutamate and the combined signals 2-{C-13}-glutamate/glutamine and 3-{C-13}-glutamate/glutamine was achieved, despite the fact that some of the associated proton resonances are close to the water signal. Two-dimensional {H-1-C-13}-spectra demonstrate the possibility of in situ spectral assignment with H-1 sensitivity and C-13 resolution. Spectroscopic images of glucose and its metabolic products were also acquired, showing the possibility to study spatial dependence of metabolism. C1 NHLBI,BETHESDA,MD 20892. NIH,INVIVO NMR RES CTR,BEIP,NCRR,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,ROCKVILLE,MD. DELFT UNIV TECHNOL,DEPT PHYS,DELFT,NETHERLANDS. RP VANZIJL, PCM (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,MRI 110,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI van Zijl, Peter/B-8680-2008; Ruiz-Cabello, Jesus/A-9570-2012 OI Ruiz-Cabello, Jesus/0000-0001-8681-5056 FU NINDS NIH HHS [NS31490] NR 26 TC 76 Z9 76 U1 1 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD NOV PY 1993 VL 30 IS 5 BP 544 EP 551 DI 10.1002/mrm.1910300504 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MC689 UT WOS:A1993MC68900003 PM 8259054 ER PT J AU GOLDMUNTZ, EA REMMERS, EF ZHA, HB MATHERN, P DU, Y CROFFORD, LJ WILDER, RL AF GOLDMUNTZ, EA REMMERS, EF ZHA, HB MATHERN, P DU, Y CROFFORD, LJ WILDER, RL TI GENETIC-MAP OF 7 POLYMORPHIC MARKERS COMPRISING A SINGLE LINKAGE GROUP ON RAT CHROMOSOME-5 SO MAMMALIAN GENOME LA English DT Article ID MOUSE; LOCI; COMMITTEE; Q22-23 AB Seven polymorphic markers comprising a single linkage group were assigned to rat Chromosome (Chr) 5 by linkage analysis of the progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. Three genes, alpha-L-fucosidase 1 (FUCA1), mitochondrial superoxide dismutase (SOD2), and glucose transporter (GLUT1), were mapped by restriction fragment length polymorphism (RFLP) analysis. Two genes, glucose transporter (GTG3) and elastase II (ELAII), one pseudogene for alpha tubulin (TUBAPS), and one sequence related to the 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase gene (PFKFBP1-related sequence) were mapped by simple sequence repeat (SSR) polymorphism analysis. The loci are in the following order: SOD2, GTG3/GLUT1, FUCA1, ELAII/PFKFBP1-related sequence, and TUBAPS. This linkage group covered 68.3 cM of rat Chr 5. The SSR markers were highly polymorphic in 13 inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUFN, WBB1/N, WBB2/N, ACI/N, LER/N, F344/N, and LEW/N). These markers, located on rat Chr 5, will be useful in genetic studies of inbred rats. RP GOLDMUNTZ, EA (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 NR 26 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1993 VL 4 IS 11 BP 670 EP 675 DI 10.1007/BF00360905 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA MF574 UT WOS:A1993MF57400008 PM 7904197 ER PT J AU RUSSELL, P KORETZ, J EPSTEIN, DL AF RUSSELL, P KORETZ, J EPSTEIN, DL TI IS PRIMARY OPEN-ANGLE GLAUCOMA CAUSED BY SMALL PROTEINS SO MEDICAL HYPOTHESES LA English DT Article ID AQUEOUS-HUMOR; CRYSTALLIN; OUTFLOW; ALPHA AB Primary open angle glaucoma is a disease which is characterized by a decreased facility of outflow of aqueous humor from the anterior segment of the eye. Analyses by gel exclusion chromatography of the aqueous humor of normal monkeys have shown that the proteins in this fluid range in size from approximately 40 - 200 kilodaltons. Although small proteins and peptides are seen in the aqueous humor by SDS gel electrophoresis, these smaller proteins appear to elute by column chromatography with the albumin peak. In the outflow of the aqueous humor, the trabecular meshwork may be an efficient sieve for proteins of intermediate size, but this tissue may be obstructed if the proteins present become too large or too small as a result of other disease processes in the eye. Primary open angle glaucoma may be the result of the inability of the trabecular meshwork to filter small proteins and polypeptides efficiently. C1 RENSSELAER POLYTECH INST,CTR BIOPHYS,TROY,NY 12181. RENSSELAER POLYTECH INST,DEPT BIOL,TROY,NY 12181. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. RP RUSSELL, P (reprint author), NEI,BLDG 6,RM 228,BETHESDA,MD 20892, USA. FU NEI NIH HHS [NEI RO1-EY-02195, NEI RO1-EY-01894] NR 18 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD NOV PY 1993 VL 41 IS 5 BP 455 EP 458 DI 10.1016/0306-9877(93)90125-A PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MH294 UT WOS:A1993MH29400010 PM 8145657 ER PT J AU RADER, DJ SCHAEFER, JR LOHSE, P IKEWAKI, K THOMAS, F HARRIS, WA ZECH, LA DUJOVNE, CA BREWER, HB AF RADER, DJ SCHAEFER, JR LOHSE, P IKEWAKI, K THOMAS, F HARRIS, WA ZECH, LA DUJOVNE, CA BREWER, HB TI INCREASED PRODUCTION OF APOLIPOPROTEIN-A-I ASSOCIATED WITH ELEVATED PLASMA-LEVELS OF HIGH-DENSITY-LIPOPROTEINS, APOLIPOPROTEIN-A-I, AND LIPOPROTEIN-A-I IN A PATIENT WITH FAMILIAL HYPERALPHALIPOPROTEINEMIA SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CORONARY-ARTERY DISEASE; POST-TRANSLATIONAL MODIFICATION; HYPER-ALPHA-LIPOPROTEINEMIA; FRACTIONAL CATABOLIC RATE; AMINO-ACID SEQUENCE; CHOLESTEROL LEVELS; TRANSGENIC MICE; INVIVO METABOLISM; HEART-DISEASE; ADIPOSE-CELLS C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. NR 55 TC 34 Z9 35 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 NOV PY 1993 VL 42 IS 11 BP 1429 EP 1434 DI 10.1016/0026-0495(93)90194-S PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG909 UT WOS:A1993MG90900009 PM 8231838 ER PT J AU SCOPA, CD MELACHRINOU, M SARADOPOULOU, C MERINO, MJ AF SCOPA, CD MELACHRINOU, M SARADOPOULOU, C MERINO, MJ TI THE SIGNIFICANCE OF THE GROOVED NUCLEUS IN THYROID LESIONS SO MODERN PATHOLOGY LA English DT Article DE GROOVED NUCLEI; THYROID LESIONS; NONPAPILLARY THYROID CONDITIONS ID PAPILLARY CARCINOMA AB Nuclear grooving has recently been accepted as a useful diagnostic criterion for papillary thyroid carcinoma. In order to determine whether this feature can serve as a reliable cytomorphologic marker of papillary carcinoma we studied, by light microscope, the surgical specimens of 80 nonpapillary thyroid lesions including 35 follicular adenomas, 8 follicular carcinomas, 5 Hurthle cell adenomas, 4 Hurthle cell carcinomas, 4 medullary carcinomas, 2 undifferentiated carcinomas, 5 cases of Hashimoto's thyroiditis, 5 diffuse hyperplasias, 2 adenomatous hyperplasias, and 10 nodular goiters. In each case, 10 random high-power fields (HPF) per slide were reviewed and the frequency of grooved nuclei per microscopic field examined and recorded. Nuclear grooves were found in all but 11 cases (one case of adenomatous hyperplasia and 10 cases of nodular goiter). Overall, 40% of the nonpapillary thyroid lesions contained nuclear grooves in more than 9 HPFs, 42% in 5 to 8 HPFs and 18% in less than 4 HPFs. Twenty four percent of the nonpapillary neoplastic lesions had eight or more grooved nuclei per HPF and 76% had six or less. The latter frequency was recorded for the 50% of the nonneoplastic thyroid conditions. Occasional intranuclear inclusions were seen in two cases of follicular tumors and in one case of Hurthle cell carcinoma. It is apparent from this study that nuclear grooving is not necessarily restricted to papillary thyroid cancer, and that it can be present in a variety of other thyroid lesions. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV PATRAS,SCH MED,DEPT PATHOL,GR-26110 PATRAI,GREECE. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 15 TC 38 Z9 39 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 1993 VL 6 IS 6 BP 691 EP 694 PG 4 WC Pathology SC Pathology GA MK431 UT WOS:A1993MK43100010 PM 8302810 ER PT J AU WILLIAMSON, KC KASLOW, DC AF WILLIAMSON, KC KASLOW, DC TI STRAIN POLYMORPHISM OF PLASMODIUM-FALCIPARUM TRANSMISSION-BLOCKING TARGET ANTIGEN PFS230 SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE PLASMODIUM FALCIPARUM; MALARIA; VACCINE; PFS230; GENE STRUCTURE; REPEAT REGION ID CIRCUMSPOROZOITE PROTEIN; ANTIBODIES; DOMAINS RP WILLIAMSON, KC (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BLDG 4,RM B1-37,BETHESDA,MD 20892, USA. NR 10 TC 26 Z9 27 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 NOV PY 1993 VL 62 IS 1 BP 125 EP 127 DI 10.1016/0166-6851(93)90186-2 PG 3 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA ML028 UT WOS:A1993ML02800016 PM 8114814 ER PT J AU MOUSSAVI, RS KELLEY, CA ADELSTEIN, RS AF MOUSSAVI, RS KELLEY, CA ADELSTEIN, RS TI PHOSPHORYLATION OF VERTEBRATE NONMUSCLE AND SMOOTH-MUSCLE MYOSIN HEAVY-CHAINS AND LIGHT-CHAINS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE MYOSIN; PHOSPHORYLATION; PROTEIN KINASES ID PROTEIN-KINASE-C; PLATELET MYOSIN; MESSENGER-RNAS; ACTIN ACTIVATION; DNA-SEQUENCE; BRAIN MYOSIN; 2ND SITE; IDENTIFICATION; CHICKEN; SERINE AB In this article we review the various amino acids present in vertebrate nonmuscle and smooth muscle myosin that can undergo phosphorylation. The sites for phosphorylation in the 20kD myosin light chain include serine-19 and threonine-18 which are substrates for myosin light chain kinase and serine-1 and/or -2 and threonine-9 which are substrates for protein kinase C. The sites in vertebrate smooth muscle and nonmuscle myosin heavy chains that can be phosphorylated by protein kinase C and casein kinase II are also summarized. Original data indicating that treatment of human T-lymphocytes (Jurkat cell line) with phorbol 12-myristate 13-acetate results in phosphorylation of both the 20 kD myosin light chain as well as the 200 kD myosin heavy chain is presented. We identified the amino acids phosphorylated in the human T-lymphocytes myosin Light chains as serine-l or serine-2 and in the myosin heavy chains as serine-1917 by 1-dimensional isoelectric focusing of tryptic phosphopeptides. Untreated T-lymphocytes contain phosphate in the serine-19 residue of the myosin light chain, and in a residue tentatively identified as serine-1944 in the myosin heavy chain. (Mel Cell Biochem 127/128: 219-227, 1993) C1 NATL HEART LUNG & BLOOD INST, MOLEC CARDIOL LAB, BETHESDA, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 50 TC 24 Z9 24 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 1993 VL 128 BP 219 EP 227 PG 9 WC Cell Biology SC Cell Biology GA MR431 UT WOS:A1993MR43100023 ER PT J AU LONERGAN, M DEY, A BECKER, KG DREW, PD OZATO, K AF LONERGAN, M DEY, A BECKER, KG DREW, PD OZATO, K TI A REGULATORY ELEMENT IN THE BETA-2-MICROGLOBULIN PROMOTER IDENTIFIED BY IN-VIVO FOOTPRINTING SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; CLASS-I GENE; INTERFERON-BETA GENE; EMBRYONAL CARCINOMA-CELLS; LIGATION-MEDIATED PCR; DNA-BINDING SUBUNIT; TRANSCRIPTION FACTOR; REL ONCOGENE; T-CELLS; INDUCIBLE ENHANCER AB Expression of the beta2-microglobulin (beta2-m) and major histocompatibility complex (MHC) class I genes is coordinately regulated. By ligation-mediated polymerase chain reaction, we have analyzed in vivo factor binding to the promoter region of the murine beta2-m gene. In adult spleen, in which beta2-m is expressed, strong protection was found in three elements. Two of these elements, the beta2-m NF-kappaB binding site and the interferon consensus sequence, are homologous to the regulatory elements of the MHC class I genes and were also found to be protected in spleen. A third protected element, PAM, identified in this work, is unique to the beta2-m gene. None of the elements showed protection in brain tissue, in which neither the beta2-m nor the MHC class I gene is expressed. In vivo footprinting was also performed with F9 embryonal carcinoma cells, in which expression of the beta2-m and MHC class I genes is induced at a low level only upon stimulation with retinoic acid (RA). No in vivo protection was detected before and after RA treatment of F9 cells, indicating that RA induction of beta2-m (and MHC class I) expression occurs without detectable in vivo factor occupancy, whereas EL4 T lymphocytes expressing beta2-m at a high level exhibited strong protection similar to that in spleen. Despite the lack of in vivo occupancy, the nuclear factors specific for each of the three elements were present in brain tissue and F9 cells as well as in spleen tissue and EL4 cells. We show that PAM, an element identified by its in vivo protection, binds nuclear factors ranging from 40 to 50 kDa in size and is capable of enhancing transcription of a reporter in F9 and other cells. Taken together, these results indicate that in vivo factor occupancy for the beta2-m and MHC class I promoters is coordinated and occurs through a mechanism other than mere expression of relevant factors. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,HOWARD HUGHES RES SCHOLARS PROGRAM,BETHESDA,MD. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 66 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 6629 EP 6639 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400003 PM 8413259 ER PT J AU DECLUE, JE VASS, WC JOHNSON, MR STACEY, DW LOWY, DR AF DECLUE, JE VASS, WC JOHNSON, MR STACEY, DW LOWY, DR TI FUNCTIONAL-ROLE OF GTPASE-ACTIVATING PROTEIN IN CELL-TRANSFORMATION BY PP60(V-SRC) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAS P21 GTPASE; SIGNAL TRANSDUCTION; TYROSINE KINASES; MOLECULAR-CLONING; SARCOMA-VIRUS; SH3 DOMAINS; V-SRC; GAP; PHOSPHORYLATION; GROWTH AB Morphological transformation of NIH 3T3 cells was observed following coexpression of a portion of the ras GTPase-activating protein (GAP) comprising the amino terminus (GAP-N) and a mutant of v-src (MDSRC) lacking the membrane-localizing sequence. Cells expressing either of these genes alone remained nontransformed. Coexpression of GAP-N with MDSRC did not alter the subcellular localization, kinase activity, or pattern of cellular substrates phosphorylated by the MDSRC product. In contrast to SHC, phospholipase C-gamma1, and the p85 alpha phosphatidylinositol 3'-kinase subunit, the endogenous GAP product (p120GAP) was highly tyrosine-phosphorylated only in cells transformed by wild-type v-src. Furthermore, for transformation induced by wild-type v-src as well as by coexpression of MDSRC and GAP-N, a strict correlation was observed between cell transformation, elevated tyrosine phosphorylation of p62, p190, and a novel protein of 150 kDa, and complex formation between these proteins and p120GAP. As with cells transformed by wild-type v-src, the MDSRC plus GA-P-N transformants remained dependent on endogenous Ras. The results suggest that tyrosine phosphorylation and complex formation involving p120GAP represent critical elements of cell transformation by v-src and that complementation of the cytosolic v-src mutant by GAP-N results, at least in part, from the formation of these complexes. C1 NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 1B26,BETHESDA,MD 20892. CLEVELAND CLIN EDUC FDN,DEPT MOLEC BIOL,CLEVELAND,OH 44106. NR 54 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 6799 EP 6809 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400019 PM 7692232 ER PT J AU PAPADOPOULOS, N CROW, MT AF PAPADOPOULOS, N CROW, MT TI TRANSCRIPTIONAL CONTROL OF THE CHICKEN CARDIAC MYOSIN LIGHT-CHAIN GENE IS MEDIATED BY 2 AT-RICH CIS-ACTING DNA ELEMENTS AND BINDING OF SERUM RESPONSE FACTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-FOS GENE; PROMOTER ELEMENTS; ENHANCER-BINDING; STRIATED-MUSCLE; XENOPUS EMBRYOS; RNA-POLYMERASE; EXPRESSION; PROTEIN; SITE; CELLS AB Transcriptional control of the cardiac/slow skeletal alkali myosin light-chain (MLC1c/1s) gene is mediated, in part, by two highly conserved AT-rich cis-acting elements present in the immediate 5' flanking region. These elements cooperate to form an enhancer that can impart tissue specificity to heterologous promoters that are themselves not tissue specific in their pattern of expression. In the chicken, one of these elements matches the binding site for myocyte-specific enhancer-binding factor 2, while the other is a cis-acting element present in the transcriptional control regions of all striated alkali MLC genes (except MLC3f) and is referred to as the MLC box. The central decanucleotide core region of the MLC box closely resembles the CArG (CC[A/T]6GG) box of the serum response element, and the binding of muscle nuclear protein complexes to this element can be competed for with a synthetic serum response element. On the basis of their competition profiles and requirements for nonspecific competitor, two nuclear protein complexes, which compete for binding to the CArG-like region of the MLC box, have been identified. One of the complexes binds to a mutation of the CArG-like region that inactivates transcription of a linked reporter gene, while binding of the other complex is inhibited by this mutation. This latter complex reacts with an antibody to serum response factor (SRF) and exhibits the same binding characteristics as purified SRF. These results demonstrate that transcriptional control of the chicken MLC1c/Is gene resides in an upstream enhancer that is composed of two separate AT-rich elements, both of which are required to drive expression of a linked reporter gene. The binding of a nuclear protein complex containing SRF to one of these elements, the MLC box, is required for gene activation and apparently inhibited by other nuclear factors whose binding overlaps that of the SRF complex. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RI Papadopoulos, Nickolas/K-7272-2012 NR 54 TC 29 Z9 30 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 NOV PY 1993 VL 13 IS 11 BP 6907 EP 6918 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400030 PM 8413283 ER PT J AU JOHNSON, PF AF JOHNSON, PF TI IDENTIFICATION OF C/EBP BASIC REGION RESIDUES INVOLVED IN DNA-SEQUENCE RECOGNITION AND HALF-SITE SPACING PREFERENCE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; LEUCINE ZIPPER PROTEINS; GENE ACTIVATOR PROTEIN; LIVER NUCLEAR-PROTEIN; AMINO-ACID CONTROL; ATF CDNA CLONES; TRANSCRIPTIONAL ACTIVATOR; YEAST GCN4; DIMERIZATION SPECIFICITY; RESPONSE ELEMENT AB C/EBP and GCN4 are basic region-leucine zipper (bZIP) DNA-binding proteins that recognize the dyadsymmetric sequences ATTGCGCAAT and ATGAGTCAT, respectively. The sequence specificities of these and other bZIP proteins are determined by their alpha-helical basic regions, which are related at the primary sequence level. To identify amino acids that are responsible for the different DNA sequence specificities of C/EBP and GCN4, two kinds of hybrid proteins were constructed: GCN4-C/EBP chimeras fused at various positions in the basic region and substitution mutants in which GCN4 basic region amino acids were replaced by the corresponding residues from C/EBP. On the basis of the DNA-binding characteristics of these hybrid proteins, three residues that contribute significantly to the differences in C/EBP and GCN4 binding specificity were defined. These residues are clustered along one face of the basic region alpha helix. Two of these specificity residues were not identified as DNA-contacting amino acids in a recently reported crystal structure of a GCN4-DNA complex, suggesting that the residues used by C/EBP and GCN4 to make base contacts are not identical. A random binding site selection procedure also was used to define the optimal recognition sequences for three of the GCN4-C/EBP fusion proteins. These experiments identify an element spanning the hinge region between the basic region and leucine zipper domains that dictates optimal half-site spacing (either directly abutted for C/EBP or overlapping by one base pair for GCN4) in high-affinity binding sites for these two proteins. RP JOHNSON, PF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NCI NIH HHS [N01-CO-74101] NR 82 TC 99 Z9 101 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 6919 EP 6930 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400031 PM 8413284 ER PT J AU BANERJEEBASU, S BUONANNO, A AF BANERJEEBASU, S BUONANNO, A TI CIS-ACTING SEQUENCES OF THE RAT TROPONIN-I SLOW GENE CONFER TISSUE-SPECIFIC AND DEVELOPMENT-SPECIFIC TRANSCRIPTION IN CULTURED MUSCLE-CELLS AS WELL AS FIBER-TYPE SPECIFICITY IN TRANSGENIC MICE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MYOGENIC DETERMINATION FACTORS; ENHANCER-BINDING-FACTOR; RECEPTOR DELTA-SUBUNIT; SKELETAL-MUSCLE; REGULATORY FACTORS; ISOFORM EXPRESSION; MAMMALIAN-CELLS; FACTOR MEF-2; MYOD FAMILY; C GENE AB Transcription of the genes coding for troponin I slow (TnI(slow)) and other contractile proteins is activated during skeletal muscle differentiation, and their expression is later restricted to specific fiber types during maturation. We have isolated and characterized the rat TnI(slow) gene in order to begin elucidating its regulation during myogenesis. Transcriptional regulatory regions were delineated by using constructs, containing TnI(slow) gene sequences driving the expression of the chloramphenicol acetyltransferase (CAT) reporter gene, that were transiently transfected into undifferentiated and differentiated C2C12 cells. TnI(slow) 5'-flanking sequences directed transcription specifically in differentiated cells. However, transcription rates were approximately 10-fold higher in myotubes transfected with constructs containing the 5'-flanking sequences plus the intragenic region residing upstream of the translation initiation site (introns 1 and 2), indicative of interactions between elements residing upstream and in the introns of the gene. Deletion analysis of the 5' region of the TnI(slow) gene showed that the 200 bp upstream of the transcription initiation site is sufficient to confer differentiation-specific transcription in C2C12 myocytes. MyoD consensus binding sites were found both in the upstream 200-bp region and in a region residing in the second intron that is highly homologous to the quail TnI(fast) enhancer. Transactivation experiments using transfected NIH 3T3 fibroblasts with TnI-CAT constructs containing intragenic and/or upstream sequences and with the myogenic factors MyoD, myogenin, and MRF4 showed different potentials of these factors to induce transcription. Transgenic mice harboring the rat TnI-CAT fusion gene expressed the reporter specifically in the skeletal muscle. Furthermore, CAT levels were approximately 50-fold higher in the soleus than in the extensor digitorum longus, gastrocnemius, or tibialis muscle, indicating that the regulatory elements that restrict TnI transcription to slow-twitch myofibers reside in the sequences we have analyzed. C1 NICHHD,DEV NEUROBIOL LAB,MOLEC NEUROBIOL UNIT,BLDG 49,ROOM 5A38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-0-2911] NR 58 TC 62 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 7019 EP 7028 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400040 PM 8413291 ER EF