FN Thomson Reuters Web of Science™ VR 1.0 PT J AU GROTHAUS, PG BIGNAMI, GS OMALLEY, S HARADA, KE BYRNES, JB WALLER, DF RAYBOULD, TJG MCGUIRE, MT ALVARADO, B AF GROTHAUS, PG BIGNAMI, GS OMALLEY, S HARADA, KE BYRNES, JB WALLER, DF RAYBOULD, TJG MCGUIRE, MT ALVARADO, B TI TAXANE-SPECIFIC MONOCLONAL-ANTIBODIES - MEASUREMENT OF TAXOL, BACCATIN-III, AND TOTAL TAXANES IN TAXUS-BREVIFOLIA EXTRACTS BY ENZYME-IMMUNOASSAY SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID WALLICHIANA ZUCC; HIGHLY EFFICIENT; PACIFIC YEW; SIDE-CHAIN; GROWTH; BARK; CANADENSIS; INITIATION; NEEDLES; CANCER AB Three monoclonal antibodies with either specificity to taxol or baccatin III, or cross-reactivity with several common taxanes have been prepared and used to develop sensitive competitive-inhibition enzyme immunoassays. The hybridomas producing these monoclonal antibodies were obtained by fusing P3X63Ag8.653 plasmacytoma cells and splenocytes from mice hyperimmunized with keyhole limper hemocyanin-7-succinyltaxol or -7-succinylbaccatin III conjugates. Direct and indirect competitive inhibition enzyme immunoassays were developed with these monoclonal antibodies and microtiter plates coated with bovine serum albumin conjugates of the complementary hapten. Detection limits for the direct competitive inhibition enzyme immunoassays, conducted in buffer containing 10% MeOH, were 0.6 nM taxol for 3C6 (anti-taxol); 1.1 nM baccatin III for 3H5 (anti-baccatin III); and 0.6 nM taxol or baccatin III for 8A 10(anti-taxane). The immunoassays accurately detected taxol, baccatin III, and ''total taxanes'' in crude MeOH extracts of Taxus brevifolia bark and in hplc fractions of these extracts. C1 NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, FREDERICK, MD 21702 USA. RP GROTHAUS, PG (reprint author), HAWAII BIOTECHNOL GRP INC, 99-193 AIEA HTS DR, AIEA, HI 96701 USA. FU NCI NIH HHS [2R44CA53060-02] NR 56 TC 27 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 1995 VL 58 IS 7 BP 1003 EP 1014 DI 10.1021/np50121a004 PG 12 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA RR649 UT WOS:A1995RR64900004 PM 7561893 ER PT J AU PENGSUPARP, T CAI, L CONSTANT, H FONG, HHS LIN, LZ KINGHORN, AD PEZZUTO, JM CORDELL, GA INGOLFSDOTTIR, K WAGNER, H HUGHES, SH AF PENGSUPARP, T CAI, L CONSTANT, H FONG, HHS LIN, LZ KINGHORN, AD PEZZUTO, JM CORDELL, GA INGOLFSDOTTIR, K WAGNER, H HUGHES, SH TI MECHANISTIC EVALUATION OF NEW PLANT-DERIVED COMPOUNDS THAT INHIBIT HIV-1 REVERSE-TRANSCRIPTASE SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Article ID IMMUNODEFICIENCY VIRUSES TYPE-1; NATURAL-PRODUCTS; DNA-POLYMERASE; DIFFERENTIAL INHIBITION; ESCHERICHIA-COLI; AIDS; SENSITIVITY; DERIVATIVES; FLAVONOIDS; SURAMIN AB Swertifrancheside [1], a new flavonone-xanthone glucoside isolated from Swertia franchetiana, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2], a triterpene isolated from the roots of Maprounea africana, and protolichesterinic acid [3], an aliphatic alpha-methylene-gamma-lactone isolated from the lichen Cetraria islandica, were found to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), with 50% inhibitory doses (IC50 values) of 43, 3.7, and 24 mu M, respectively. They were nor cytotoxic with cultured mammalian cells. The kinetic mechanisms by which compounds 1-3 inhibited HIV-1 RT were studied as was their potential to inhibit other nucleic acid polymerases. Swertifrancheside [1] bound to DNA and was shown ro be a competitive inhibitor with respect to template-primer, but a mixed-type competitive inhibitor with respect to TTP. On the other hand, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic acid [3] were mixed-type competitive inhibitors with respect to template-primer and noncompetitive inhibitors with respect to TTP. Therefore, the mechanism of action of 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and protolichesterinic acid [3] as HIV-1 RT inhibitors involves nonspecific binding to the enzyme at nonsubstrate binding sites, whereas swertifrancheside [1] inhibits enzyme activity by binding to the template-primer. C1 UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60612. UNIV ICELAND,DEPT PHARM,IS-101 REYKJAVIK,ICELAND. UNIV MUNICH,INST PHARMACEUT BIOL,D-80333 MUNICH,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Kinghorn, A. Douglas/0000-0002-6647-8707 FU NCI NIH HHS [N01-CO-74101, P01 CA48112, R01 CA20164] NR 34 TC 56 Z9 60 U1 0 U2 2 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD JUL PY 1995 VL 58 IS 7 BP 1024 EP 1031 DI 10.1021/np50121a006 PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA RR649 UT WOS:A1995RR64900006 PM 7561895 ER PT J AU BEUTLER, JA KASHMAN, Y TISCHLER, M CARDELLINA, JH GRAY, GN CURRENS, MJ WALL, ME WANI, MC BOYD, MR AF BEUTLER, JA KASHMAN, Y TISCHLER, M CARDELLINA, JH GRAY, GN CURRENS, MJ WALL, ME WANI, MC BOYD, MR TI HIV-INHIBITORY NATURAL-PRODUCTS .23. A REINVESTIGATION OF MAPROUNEA TRITERPENES SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Article ID TYPE-1 REVERSE-TRANSCRIPTASE; QUINATA CALLUS-TISSUE; ESCHERICHIA-COLI; PHORBOL; AFRICANA; ACIDS AB Anti-HIV activity and the inhibition of phorbol ester receptor binding activity in two species of Maprounea were traced to small amounts of highly potent phorbol esters of the daphnane type. The triterpenes previously isolated from this genus were found to be devoid of biological activity when scrupulously purified. Four new triterpene esters were elucidated; two [3,4] were found in M. africana, while three [4,6,7] were found in M. membranacea. Nmr assignments have also been made for two previously known compounds [2,5] in this group. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 35 TC 17 Z9 18 U1 0 U2 3 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD JUL PY 1995 VL 58 IS 7 BP 1039 EP 1046 DI 10.1021/np50121a008 PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA RR649 UT WOS:A1995RR64900008 PM 7561897 ER PT J AU RASHID, MA GUSTAFSON, KR CARDELLINA, JH BOYD, MR AF RASHID, MA GUSTAFSON, KR CARDELLINA, JH BOYD, MR TI MYCALOLIDE-D AND MYCALOLIDE-E, NEW CYTOTOXIC MACROLIDES FROM A COLLECTION OF THE STONY CORAL TUBASTREA-FAULKNERI SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Note ID BIOACTIVE MARINE METABOLITES; SPONGE; HALICHONDRAMIDE; APLYSINOPSIN; AUREA AB Fractionation of a cytotoxic extract of the stony coral Tubastrea faulkneri yielded a series of cytotoxic polyoxazole macrolides and several noncytotoxic indole derivatives. Two new macrolides, mycalolides D [1] and E [2], were isolated and identified, in addition to the known compound mycalolide C [3]. The macrolide structures were elucidated by derailed analysis of their spectroscopic data and by comparison with related compounds. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 20 TC 48 Z9 49 U1 0 U2 7 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD JUL PY 1995 VL 58 IS 7 BP 1120 EP 1125 DI 10.1021/np50121a025 PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA RR649 UT WOS:A1995RR64900025 PM 7561903 ER PT J AU CORWIN, RL JORN, A HARDY, M CRAWLEY, JN AF CORWIN, RL JORN, A HARDY, M CRAWLEY, JN TI THE CCK-B ANTAGONIST CI-988 INCREASES DOPAMINE LEVELS IN MICRODIALYSATE FROM THE RAT NUCLEUS-ACCUMBENS VIA A TETRODOTOXIN-INDEPENDENT AND CALCIUM-INDEPENDENT MECHANISM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE IN VIVO MICRODIALYSIS; CHOLECYSTOKININ; RELEASE; RECEPTOR; NEUROPEPTIDE; MESOLIMBIC ID CHOLECYSTOKININ OCTAPEPTIDE; SULFATED CHOLECYSTOKININ; EXTRACELLULAR DOPAMINE; RECEPTOR ANTAGONISTS; INVIVO RELEASE; AMPHETAMINE; STRIATUM; NEURONS; BRAIN; 1-METHYL-4-PHENYLPYRIDINIUM AB Cl-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of Cl-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the Cl-988 perfusion and returned to baseline levels upon cessation of Cl-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of Cl-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of Cl-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered Cl-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NR 41 TC 8 Z9 8 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 JUL PY 1995 VL 65 IS 1 BP 208 EP 217 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX166 UT WOS:A1995RX16600025 PM 7790862 ER PT J AU ACS, G LEE, J MARQUEZ, VE WANG, SM MILNE, GWA DU, L LEWIN, NE BLUMBERG, PM AF ACS, G LEE, J MARQUEZ, VE WANG, SM MILNE, GWA DU, L LEWIN, NE BLUMBERG, PM TI RESINIFERATOXIN-AMIDE AND ANALOGS AS LIGANDS FOR PROTEIN-KINASE-C AND VANILLOID RECEPTORS AND DETERMINATION OF THEIR BIOLOGICAL-ACTIVITIES AS VANILLOIDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE RESINIFERATOXIN; VANILLOID RECEPTOR; PROTEIN KINASE C ID PRIMARY AFFERENT NEURONS; ROOT GANGLION MEMBRANES; ANALGESIC AGENTS; AGONIST ACTIVITY; POLYFUNCTIONAL DITERPENES; CAPSAICIN CONGENERS; CHEMICAL-STRUCTURE; SENSORY NEURONS; BINDING; ESTERS AB The naturally occurring diterpene resiniferatoxin (RTX) is an ultrapotent analogue of capsaicin. Acting on polymodal afferent neurons, RTX induces a generally similar pattern of responses as does capsaicin. However, the two compounds, as well as other vanilloid derivatives, display different relative potencies for different responses. In the present study, we examined the vanilloid-like activities of two new derivatives, the amide analogue of RTX and phorbol 12,13-dibenzoate 20-homovanillylamide. Structurally, RTX-amide resembles capsaicin more closely than does RTX, and after cleavage of the amide bond the resulting amine would be predicted to not bind to protein kinase C in contrast to resiniferonol 9,13,14-orthophenylacetate, the parent diterpene of RTX. In contrast to our expectations the binding potency of the RTX-amide for the vanilloid receptor present in rat spinal cord was 450-fold lower than that of RTX (Ki values for the RTX-amide and RTX were 10.4 +/- 0.7 nM and 23.1 +/- 3.2 pM, respectively). In the case of phorbol 12,13-dibenzoate 20-homovanillylamide, there was a further loss of affinity for the vanilloid receptor compared with RTX; nonetheless, the K-i (8.56 +/- 0.61 mu M) was comparable with that of capsaicin (5.31 +/- 0.37 mu M). Computer fitting of the binding data yielded Hill coefficient values of 2.25 +/- 0.03, 2.33 +/- 0.03, and 1.84 +/- 0.05 for RTX, RTX-amide, and phorbol 12,13-dibenzoate 20-homovanillylamide, respectively, indicating that both new compounds induced apparent positive cooperativity among vanilloid binding sites. We found that the RTX-amide was also 20- and 300-fold less potent than RTX in inducing chemogenic pain and hypothermia, respectively. The affinities of the compounds for protein kinase C-alpha were evaluated by competition of [H-3] phorbol 12,13-dibutyrate binding. Replacement of the C-20 hydroxyl group in phorbol 12,13-dibenzoate by an amine led to a 750-fold drop in binding affinity, and the conversion of the phorbol 12,13-dibenzoate 20-amine to the amide resulted in a further 60-fold drop in binding activity (K-i values for phorbol 12,13-dibenzoate, phorbol 12,13-dibenzoate 20-amine, and phorbol 12,13-dibenzoate 20-homovanillylamide were 0.96 +/- 0.01, 720 +/- 80, and 43,500 +/- 4,060 nM, respectively). The K-i of the RTX-amide for protein kinase C-alpha was > 100 mu M, whereas RTX and the parent alcohol resiniferonol 9,13,14-orthophenylacetate yielded K-i values of 1.49 +/- 0.19 mu M and 36.5 +/- 1.3 nM, respectively. C1 NCI, DIV CANC ETIOL, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, MOLEC MECH TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, MED CHEM LAB, BETHESDA, MD 20892 USA. NR 48 TC 23 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1995 VL 65 IS 1 BP 301 EP 308 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX166 UT WOS:A1995RX16600038 PM 7790875 ER PT J AU WINSKY, L KUZNICKI, J AF WINSKY, L KUZNICKI, J TI DISTRIBUTION OF CALRETININ, CALBINDIN D28K, AND PARVALBUMIN IN SUBCELLULAR-FRACTIONS OF RAT CEREBELLUM - EFFECTS OF CALCIUM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CALCIUM-BINDING PROTEINS; CEREBELLUM; CAUDATE; SUBCELLULAR FRACTIONS ID BINDING PROTEIN PARVALBUMIN; ULTRASTRUCTURAL-LOCALIZATION; IMMUNOHISTOCHEMICAL LOCALIZATION; NERVOUS-SYSTEM; BRAIN; CELLS; NEURONS; CALMODULIN; IMMUNOREACTIVITY; PHOSPHORYLATION AB The distribution of calretinin, calbindin D28k, and parvalbumin was examined in subcellular fractions prepared from rat cerebellum and analyzed by immunoblot. Calretinin was also quantified by radioimmunoassay, As expected, all three soluble, EF-hand calcium-binding proteins were predominantly localized in the cytosolic fraction. Calretinin and calbindin D28k were also detected in membrane fractions. Calretinin was more abundant in synaptic membrane than in microsomal fractions. The cerebellar microsomal fraction contained the greatest concentration of membrane-associated calbindin D28k. The association of calretinin and calbindin D28k with membrane fractions was decreased in samples prepared or incubated in low calcium. Quantification of calretinin in subcellular fractions of rat cerebellum revealed a greater amount of calretinin in cytosolic fractions prepared or incubated in low calcium and reduced amounts of calretinin in all membrane fractions incubated in low calcium with the exception of the mitochondrial fraction, These results imply that calretinin and calbindin D28k might have physiological target molecules that are associated with, or are components of, brain membranes. RP WINSKY, L (reprint author), NIMH,CLIN SCI LAB,RM 3D-48,10 CTR DR,MSC 1266,BETHESDA,MD 20892, USA. NR 57 TC 71 Z9 71 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1995 VL 65 IS 1 BP 381 EP 388 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX166 UT WOS:A1995RX16600047 PM 7790883 ER PT J AU TAKAHASHI, S COOK, M JEHLE, J KENNEDY, C SOKOLOFF, L AF TAKAHASHI, S COOK, M JEHLE, J KENNEDY, C SOKOLOFF, L TI LACK OF EFFECTS OF INHIBITION OF NITRIC-OXIDE SYNTHESIS ON LOCAL GLUCOSE-UTILIZATION IN THE RAT-BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE [C-14] DEOXYGLUCOSE; N-G-NITRO-L-ARGININE METHYL ESTER; CEREBRAL ENERGY METABOLISM; NITRIC OXIDE SYNTHASE ID CEREBRAL BLOOD-FLOW; NEURONAL MESSENGER; RELAXING FACTOR; NERVOUS-SYSTEM; SYNTHASE; LOCALIZATION; METABOLISM AB The effects of chronic treatment with N-G-nitro-L-arginine methyl ester, a potent inhibitor of nitric oxide synthase activity, on local cerebral glucose utilization were examined in conscious rats. Intraperitoneal injections of 50 mg/kg of the nitroarginine twice daily for 4 days have been found to result in almost complete inhibition of nitric oxide synthase activity in brain. Local cerebral glucose utilization was determined by means of the quantitative autoradiographic [C-14]deoxyglucose method in an experimental group (n = 7) of rats that were treated with the nitroarginine according to this schedule and in a normal control group (n = 7) treated similarly with saline. The rats were conscious but partially restrained during the determinations of local cerebral glucose utilization. The nitroarginine treatment raised mean arterial blood pressure statistically significantly to 147 +/- 3 mm Hg (mean +/- SEM) from a level of 120 +/- 5 mm Hg in the saline controls (p < 0.001 by grouped t test), but there were no statistically significant effects on glucose utilization in any of 39 brain structures examined. It is concluded that nitric oxide normally exerts no significant influence on energy metabolism in the rat brain. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RI Takahashi, Shinichi/L-3454-2013 NR 36 TC 11 Z9 11 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 JUL PY 1995 VL 65 IS 1 BP 414 EP 419 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX166 UT WOS:A1995RX16600051 PM 7790888 ER PT J AU OSHIMA, M WEISS, L DOUGALL, WC GREENE, MI GUROFF, G AF OSHIMA, M WEISS, L DOUGALL, WC GREENE, MI GUROFF, G TI DOWN-REGULATION OF C-NEU RECEPTORS BY NERVE GROWTH-FACTOR IN PC12 CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PC12 CELLS; NERVE GROWTH FACTOR; ERBB2 RECEPTOR; NEU RECEPTOR ID HUMAN-BREAST-CANCER; EGF RECEPTOR; TYROSINE PHOSPHORYLATION; PHEOCHROMOCYTOMA CELLS; MONOCLONAL-ANTIBODIES; ONCOGENE PRODUCT; PROTO-ONCOGENE; GENE-PRODUCT; LIGAND; HEREGULIN AB A small number of p185(c-neu) receptors have been found on PC12 cells. These receptors show some basal phosphorylation in quiescent cells. When the cells are treated with nerve growth factor (NGF) for a short time, some increase in phosphorylation is seen, mainly on serine and threonine residues, and this is accompanied by a slight shift in the apparent molecular weight. Epidermal growth factor (EGF) also increases the phosphorylation of p185(c-neu), in this case on tyrosine residues. Neither heregulin-beta 1 nor gp30 stimulates the tyrosine phosphorylation of p185(c-neu), and neither has a proliferative effect on the cells. Treatment of the cells with NGF for 5 days produces a 70-80% reduction in the number of p185(c-neu) receptors. This down-regulation does not occur when PC12nnr5 cells, which lack the high-affinity NGF receptor, p140(trk) are treated with NGF. The level of p185(c-neu) mRNA is not altered by NGF treatment, suggesting that the down-regulation is due to either a translational or a posttranslational alteration. C1 NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RI Weiss, Linnea/K-8062-2014 NR 40 TC 12 Z9 12 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 JUL PY 1995 VL 65 IS 1 BP 427 EP 433 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX166 UT WOS:A1995RX16600053 PM 7790889 ER PT J AU DACUNHA, A JACKSON, RW VITKOVIC, L AF DACUNHA, A JACKSON, RW VITKOVIC, L TI HIV-1 NONSPECIFICALLY STIMULATES PRODUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSFER IN PRIMARY ASTROCYTES SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1; ASTROCYTE; TRANSFORMING GROWTH FACTOR BETA-1; ENDOCYTOSIS; PHAGOCYTOSIS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; FACTOR-BETA; NERVOUS-SYSTEM; GOLGI-COMPLEX; BRAIN-TISSUE; GLIAL-CELLS; T-CELL; EXPRESSION; INFECTION AB HIV-1 expression in monocytes/macrophages can be controlled by transforming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 is present in astrocytes surrounding HIV-l-infected monocyte/macrophages in brain tissue from patients with AIDS but not from seronegative, normal individuals. We sought to determine whether or not production of TGF-beta 1 can be directly stimulated by HIV-1 in astrocytes. Astrocytes from neonatal rat cortex grown in primary culture were exposed to HIV-I virions for 24 h. One day later, TGF-beta 1 was measured in culture supernatants by a biological assay. HIV-1 caused 1.7-2.1-fold increase in extracellular concentration of TGF-beta 1. TGF-beta 1 production also was stimulated by recombinant HIV-I proteins gp120, p66 and p24. Gp120 labeled with fluorescein was visualized inside astrocytes and its stimulatory effect was not blocked by antibodies against rat CD4. The effect was not specific to HIV-1 and its proteins, because non-opsonized Latex particles and leucine methyl ester (LME) (known to be phagocytosed and endocytosed, respectively, by astrocytes) also stimulated TGF-beta 1 production. The effect was inhibited by two inhibitors of the phago/endocytotic pathway, chloroquine and leupeptin. These results may be relevant to the neuropathogenesis of HIV-1 infection. C1 NIMH,DIV NEUROSCI & BEHAV SCI,ROCKVILLE,MD 20857. NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 45 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 1995 VL 60 IS 1-2 BP 125 EP 133 DI 10.1016/0165-5728(95)00062-7 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA RP059 UT WOS:A1995RP05900015 PM 7642740 ER PT J AU NORDLUND, ML RIZVI, TA BRANNAN, CI RATNER, N AF NORDLUND, ML RIZVI, TA BRANNAN, CI RATNER, N TI NEUROFIBROMIN EXPRESSION AND ASTROGLIOSIS IN NEUROFIBROMATOSIS (TYPE-1) BRAINS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ASTROCYTE; DEGENERATION; GFAP; NEUROFIBROMIN; NF1; RAS ID GTPASE-ACTIVATING PROTEIN; FIBRILLARY ACIDIC PROTEIN; ALZHEIMERS-DISEASE; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; SACCHAROMYCES-CEREVISIAE; GENE-PRODUCT; RAS GTPASE; WHITE MATTER; MR FINDINGS; PC12 CELLS AB Patients with type 1 neurofibromatosis (NF1) have mutations in the gene encoding the protein neurofibromin. Immunocytochemistry on sections of cortex and cerebellum of unaffected and NF1 individuals and wild-type and NF1-deficient mice showed that: the distribution of neurofibromin was similar to that reported for rat. However, dystrophic neurofibromin-expressing neurons were found in human but not rodent brain. Intensity of anti-neurofibromin reactivity was reduced in NF1-deficient mice but not in human brains. GFAP was upregulated in three NF1 brains studied by immunocytochemistry; a 4-18-fold increase in GFAP levels was documented by Western blot analysis in three brains. GFAP content/cell and the number of GFAP-immunoreactive astrocytes was increased in NF1 brains as compared to the controls. These results suggest that mutations in the NF1 gene do not grossly alter the pattern of neurofibromin expression, but activation of astrocytes may be common in NF1. Presence of degenerative debris in one of two brains using the cupric silver method suggests that degeneration is not always detectable in NF1 brains. C1 UNIV CINCINNATI,COLL MED,DEPT CELL BIOL NEUROBIOL & ANAT,CINCINNATI,OH 45267. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD. FU NINDS NIH HHS [NS28840] NR 75 TC 53 Z9 53 U1 0 U2 3 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 1995 VL 54 IS 4 BP 588 EP 600 DI 10.1097/00005072-199507000-00013 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA RH641 UT WOS:A1995RH64100013 PM 7602332 ER PT J AU WALLACE, WC LIEBERBURG, I SCHENK, D VIGOPELFREY, C DAVIS, KL HAROUTUNIAN, V AF WALLACE, WC LIEBERBURG, I SCHENK, D VIGOPELFREY, C DAVIS, KL HAROUTUNIAN, V TI CHRONIC ELEVATION OF SECRETED AMYLOID PRECURSOR PROTEIN IN SUBCORTICALLY LESIONED RATS, AND ITS EXACERBATION IN AGED RATS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AMYLOID PRECURSOR PROTEIN; SUBCORTICAL LESIONS; CHOLINERGIC SYSTEM; SEROTONERGIC SYSTEM; RAT BRAIN; IN VIVO SECRETION ID FAMILIAL ALZHEIMERS-DISEASE; NUCLEUS BASALIS; BETA-PROTEIN; SENILE DEMENTIA; CEREBRAL-CORTEX; PEPTIDE; GENE; MUTATION; FOREBRAIN; CLEAVAGE AB Subcortically lesioned rats were used as an animal model of some of the neurochemical and behavioral deficits of Alzheimer's disease (AD) to investigate the in vivo expression and metabolism of amyloid precursor protein (APP), Previously, the rapid and persistent induction of APP was described in cerebral cortices after disruption of its cholinergic, serotonergic, or noradrenergic afferents, In the present study, this induction was found to lead to the elevated secretion of APP into the cerebrospinal fluid of lesioned animals, Lesions of the forebrain cholinergic system in aged rats caused an even greater increase in the CSF levels of secreted APP, Antibodies to the extracellular domain of APP detected the protein whereas antibodies to the cytoplasmic region did not, indicating that the APP present in CSF was of the soluble form, Immunoprecipitation with an A beta sequence-specific antibody followed by immunoblot analysis indicated that a significant portion of secreted APP was of the species that contains at least the first 28 amino acids of the A beta sequence (APP(gamma) or APP(A beta)). By contrast, very low levels of A beta peptide were detected in CSF, The secretion was accompanied by an elevation of cellular C-terminal fragments of the APP in the lesioned cortex, Consistent with our previous results, this increased APP secretion was caused by lesions of subcortical cholinergic and serotonergic systems, The postlesion time course of APP secretion showed an initial reduction of APP (1 hr postlesion) in CSF followed by an eventual twofold elevation 1-6 weeks later. These results indicate that the induction of APP in response to loss of subcortical innervation leads to elevated secretion of a soluble form of cortically derived APP that contains significant portions of the A beta sequence. C1 NIMH,BIOCHEM GENET LAB,WASHINGTON,DC. ATHENA NEUROSCI,SAN FRANCISCO,CA. MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY. VET ADM MED CTR,BRONX,NY 10468. FU NIA NIH HHS [R01 AG10138] NR 42 TC 43 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1995 VL 15 IS 7 BP 4896 EP 4905 PN 1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA RJ662 UT WOS:A1995RJ66200016 PM 7623120 ER PT J AU TOMBRANTINK, J SHIVARAM, SM CHADER, GJ JOHNSON, LV BOK, D AF TOMBRANTINK, J SHIVARAM, SM CHADER, GJ JOHNSON, LV BOK, D TI EXPRESSION, SECRETION, AND AGE-RELATED DOWN-REGULATION OF PIGMENT EPITHELIUM-DERIVED FACTOR, A SERPIN WITH NEUROTROPHIC ACTIVITY SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SERPIN; NEUROTROPHIC FACTOR; PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF); AGING; CYTOSKELETAL STRUCTURE; NEURAL RETINA; PIGMENT EPITHELIUM; INTERPHOTORECEPTOR MATRIX; ACTIN; TISSUE CULTURE ID RETINOBLASTOMA CELLS; CONDITIONED MEDIUM; NEURITE OUTGROWTH; GROWTH-FACTOR; DIFFERENTIATION; PROTEINS; INVITRO; INHIBITOR; PRODUCE; RELEASE AB Retinal pigment epithelial (RPE) cells form a functional complex with photoreceptor neurons of the retina, interacting through the interphotoreceptor matrix (IPM). We now provide evidence that the gene for pigment epithelium-derived factor (PEDF), a protein possessing neurotrophic and neuronal-survival activities, is highly expressed by both fetal and young adult RPE cells. PEDF mRNA is present in RPE cells of the human eye at 17 weeks of gestation, demonstrating its potential for action in vivo during early retinal development. The PEDF protein is secreted in vivo where it constitutes a part of the fetal and adult IPM surrounding photoreceptor outer segments. A polyclonal PEDF antibody recognizes at least four isoforms of secreted human and bovine PEDF by two dimensional gel analysis, and detects a similar 50 kDa protein in the IPM of several other vertebrate species. Within soluble extracts of RPE cells, however, where little, if any, of the 50 kDa species can be detected, an immunoreactive 36 kDa protein is observed by Western blot analysis. By immunofluorescence, PEDF is localized intracellularly in association with the nucleus, presumptive secretory granules, and cytoskeletal elements of cultured RPE cells with PEDF and actin antibodies colocalizing to the same cytoskeletal structures. During initial stages of attachment, PEDF and actin also concentrate at the tips of pseudopods extended by the cultured RPE cells. However, with successive passages, synthesis, and secretion of the PEDF protein as well as transcription of its mRNA decrease and are lost by about 10 passages. In parallel, cultured RPE cells lose their proliferative potential and change from an epithelial-like morphology in early passages to a more fibroblast-like appearance by about the 10th passage. PEDF is thus apparently present intracellularly and extracellularly in both fetal and early adult periods where it could be involved in cellular differentiation and survival and with its loss, in the onset of senescence. C1 HOWARD HUGHES MED INST,BETHESDA,MD 20814. UNIV SO CALIF,SCH MED,DEPT CELL & NEUROBIOL,LOS ANGELES,CA 90033. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,JULES STEIN EYE INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. RP TOMBRANTINK, J (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 311,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY00331, EY00444, EY04741] NR 48 TC 146 Z9 153 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1995 VL 15 IS 7 BP 4992 EP 5003 PN 1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA RJ662 UT WOS:A1995RJ66200024 PM 7623128 ER PT J AU DUFFY, CJ WURTZ, RH AF DUFFY, CJ WURTZ, RH TI RESPONSE OF MONKEY MST NEURONS TO OPTIC FLOW STIMULI WITH SHIFTED CENTERS OF MOTION SO JOURNAL OF NEUROSCIENCE LA English DT Article DE VISUAL SYSTEM; MOTION; OPTIC FLOW; EXTRASTRIATE CORTEX; MST; MONKEY; FOE ID SUPERIOR TEMPORAL SULCUS; MACAQUE MONKEY; EYE-MOVEMENTS; EXPANSION CONTRACTION; ROTATION CELLS; FIELD STIMULI; VISUAL AREAS; IMAGE MOTION; SELF-MOTION; DORSAL PART AB Neurons in the dorsal region of the medial superior temporal area (MSTd) have previously been shown to respond to the expanding radial motion that occurs as an observer moves through the environment, In previous experiments, MSTd neurons were tested with radial and circular motion centered in the visual field, However, different directions of observer motion, relative to the direction of gaze, are accompanied by visual motion centered at different locations in the visual field, The present experiments investigated whether neurons that respond to radial and circular motion might respond differently when the center of motion was shifted to different regions of the visual field, About 90% of the 245 neurons studied responded differently when the center of motion was shifted away from the center of the field, The centers of motion preferred by each neuron were limited to one area of the visual field, All parts of the visual field were represented in the sample, with greater numbers of neurons preferring centers of motion closer to the center of the field, We hypothesize that each of the MSTd neurons has a center of motion field with a gradient of preferred centers of motion, and that there is an orderly arrangement of MSTd neurons with each region of the visual field being represented by a set of neurons, This arrangement creates the potential for graded responses from individual neurons for different directions of heading as an observer moves through the environment. C1 NEI, SENSORIMOTOR RES LAB, BETHESDA, MD 20892 USA. NR 48 TC 240 Z9 241 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1995 VL 15 IS 7 BP 5192 EP 5208 PN 2 PG 17 WC Neurosciences SC Neurosciences & Neurology GA RJ666 UT WOS:A1995RJ66600010 PM 7623145 ER PT J AU FUKUYAMA, R BRADY, DR RAPOPORT, SI AF FUKUYAMA, R BRADY, DR RAPOPORT, SI TI DEVELOPMENT AND APPLICATION OF A MODIFIED MONOCLONAL HYBRIDOMA TECHNIQUE FOR ISOLATING MONOCLONAL-ANTIBODIES TO HUMAN BRAIN-REGIONS SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE HYBRIDOMA; ANTIBODY; ENTORHINAL CORTEX; WESTERN BLOT; REGIONAL VULNERABILITY ID CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; CYTOCHROME-OXIDASE; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; INVITRO IMMUNIZATION; ENTORHINAL CORTEX; MESSENGER-RNA; MONKEY BRAIN; LOCALIZATION AB We developed a modified monoclonal hybridoma technique that combines two conventional methods: a conventional immunosuppression method with cyclophosphamide treatment and an in vitro immunization method. This technique is advantageous over conventional methodologies because it requires a shorter period for immunization of mice and a smaller quantity of antigen, and gives rise to antibody-secreting hybridomas with higher efficiency. One monoclonal hybridoma line, designated as BG5, was established by this technique after activation of lymphocytes with muramyl dipeptide and with the immunogen obtained from human entorhinal cortex. Western blot analysis showed a relatively high expression of BG5 antigen in human entorhinal cortex. Our results suggest that this modified hybridoma technique may rapidly facilitate the acquisition of brain region-specific antibodies. We call this technique 'suppression immunization followed by in vitro stimulation procedure' (SOFISTIC). RP FUKUYAMA, R (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 39 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL PY 1995 VL 59 IS 2 BP 199 EP 204 DI 10.1016/0165-0270(94)00183-H PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ995 UT WOS:A1995RQ99500006 PM 8531487 ER PT J AU BURT, RK BURNS, W RUVOLO, P FISCHER, A SHIAO, C GUIMARAES, A BARRETT, J HESS, A AF BURT, RK BURNS, W RUVOLO, P FISCHER, A SHIAO, C GUIMARAES, A BARRETT, J HESS, A TI SYNGENEIC BONE-MARROW TRANSPLANTATION ELIMINATES V-BETA-8.2 T-LYMPHOCYTES FROM THE SPINAL-CORD OF LEWIS RATS WITH EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; MS; MBP ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; TOTAL-BODY IRRADIATION; MYELIN BASIC-PROTEIN; CELL RECEPTORS; BETA-CHAIN; DISEASES; MICE; GENES; BMT AB Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP), Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery, Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V(beta)8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V(beta)8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization, In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V(beta)8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin. (C) 1995 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BONE MARROW TRANSPLANTAT UNIT,BALTIMORE,MD. RP BURT, RK (reprint author), NHLBI,CLIN HEMATOL BRANCH,BONE MARROW TRANSPLANTAT UNIT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. NR 32 TC 34 Z9 36 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 1995 VL 41 IS 4 BP 526 EP 531 DI 10.1002/jnr.490410412 PG 6 WC Neurosciences SC Neurosciences & Neurology GA RG043 UT WOS:A1995RG04300011 PM 7473884 ER PT J AU OLDFIELD, EH AFSHAR, J DICHIRO, G DOPPMAN, JL AF OLDFIELD, EH AFSHAR, J DICHIRO, G DOPPMAN, JL TI COMPLIMENTS TO NIH - RESPONSE SO JOURNAL OF NEUROSURGERY LA English DT Letter RP OLDFIELD, EH (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 1995 VL 83 IS 1 BP 185 EP 185 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RE609 UT WOS:A1995RE60900040 ER PT J AU KNABLE, MB JONES, DW COPPOLA, R HYDE, TM LEE, KS GOREY, J WEINBERGER, DR AF KNABLE, MB JONES, DW COPPOLA, R HYDE, TM LEE, KS GOREY, J WEINBERGER, DR TI LATERALIZED DIFFERENCES IN IODINE-123-IBZM UPTAKE IN THE BASAL GANGLIA IN ASYMMETRIC PARKINSONS-DISEASE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PARKINSONS DISEASE; IODINE-123-IBZM; SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY; DOPAMINE RECEPTORS ID POSITRON EMISSION TOMOGRAPHY; PROGRESSIVE SUPRANUCLEAR PALSY; RECEPTOR IMAGING AGENT; DOPAMINE-RECEPTORS; I-123 IBZM; COMPUTED-TOMOGRAPHY; D2 RECEPTORS; D(2)-DOPAMINE RECEPTORS; HUMAN-BRAIN; INVIVO AB We used equilibirium analysis of SPECT data from patients with asymmetric Parkinson's disease to determine if lateralized differences in the striatal uptake of [I-123]IBZM correlate with asymmetry in clinical findings and, by inference, with lateralized differences in the concentration of extracellular dopamine. Methods: Twelve patients with asymmetric clinical signs of idiopathic Parkinson's disease were injected with a bolus of [I-123]IBZM, and multiple SPECT scans recorded the time course of radioligand uptake. The time integral method was used to estimate peak specific binding, so that a ratio of specific-to-nonspecific binding in the left and right striatum of each subject at equilibium could be determined. Nine patients also had Tc-99m-HMPAO SPECT scans which were examined for evidence of blood flow asymmetries. Results: Paired t-tests comparing [I-123]IBZM uptake revealed significantly greater (mean = 7.3%) availability of dopamine-D2 receptors in the basal ganglia contralateral to maximal clinical signs. Differences in receptor availability correlated significantly with differences in every measure of the clinical assessment. No significant differences in regional cerebral blood flow between the two sides were observed with Tc-99m-HMPAO. Conclusion: These results demonstrate the ability of [I-123]lBZM SPECT to reveal clinically meaningful variations in striatal dopamine receptor availability in patients with asymmetric Parkinson's disease. The equilibirum analysis technique used to determine these findings is a simple and robust method of measuring relative receptor availability and may be useful in studying other illnesses where dysfunction of dopaminergic neurotransmission is suspected. C1 NIH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP KNABLE, MB (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 41 TC 47 Z9 47 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1995 VL 36 IS 7 BP 1216 EP 1225 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RG113 UT WOS:A1995RG11300020 PM 7790947 ER PT J AU BARABINO, A COSTANTINI, M CICCONE, MO PESCE, F PARODI, B GATTI, R AF BARABINO, A COSTANTINI, M CICCONE, MO PESCE, F PARODI, B GATTI, R TI RELIABILITY OF SHORT-TERM ESOPHAGEAL PH MONITORING VERSUS 24-HOUR STUDY SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE ESOPHAGEAL PH MONITORING; GER DISEASE ID GASTROESOPHAGEAL REFLUX; CHILDREN; INFANTS AB The child's discomfort and the cost of overnight hospitalization are clear disadvantages of prolonged esophageal pH monitoring. The aim of this study was to verify the reliability of short recording versus 24-h testing in a pediatric series with symptoms suggestive of gastroesophageal reflux (GER) disease. A 24-h pH monitoring performed on 160 patients with either gastroenterological symptoms (n = 61), respiratory problems (n = 58), or emesis plus respiratory problems (n = 41) was reviewed. Regardless of clinical presentation, children were also classified according to age: <12 months (n = 39), 12-71 months (n = 81), and 72-168 months (n = 40). A diurnal fraction of 6 h, including at least 2 h after a meal, was compared to the entire 24-h recording in all groups with respect to the reflux index (RI) (sum of the periods with pH <3.9 expressed as percentage of time) and reflux/h. RIs of >10% were considered positive in patients <1 year of age, whereas RIs of >5% were considered positive in other age groups. Negative predictive values of the short recording RI ranged from 71 to 90%. Positive predictive values ranged from 50 to 83%; it was unreliable for children <12 mos (50%) and patients with emesis plus respiratory problems (64%), who were, significantly, the youngest. Reflux/h values were not in agreement for the same groups. Absence of agreement was found if the absolute value of RI was considered. In conclusion, our data show that short-term recordings may be used as an ambulatory screening test for GER in selected children, being unreliable for patients <1 year of age and for those presenting with both gastroenterological and respiratory symptoms. C1 NATL CANC INST,CLIN EPIDEMIOL & TRIALS UNIT,GENOA,ITALY. RP BARABINO, A (reprint author), IST GIANNINA GASLINI,DEPT PEDIAT 3,LARGO G GASLINI 5,I-16148 GENOA,ITALY. RI costantini, massimo/G-1443-2012 NR 9 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 1995 VL 21 IS 1 BP 87 EP 90 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA RJ016 UT WOS:A1995RJ01600015 PM 8576821 ER PT J AU DOMANSKI, MJ SLOAS, MM FOLLMANN, DA SCALISE, PP TUCKER, EE EGAN, D PIZZO, PA AF DOMANSKI, MJ SLOAS, MM FOLLMANN, DA SCALISE, PP TUCKER, EE EGAN, D PIZZO, PA TI EFFECT OF ZIDOVUDINE AND DIDANOSINE TREATMENT ON HEART FUNCTION IN CHILDREN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF PEDIATRICS LA English DT Article ID LONGITUDINAL DATA; MYOPATHY AB Objectives: Human immunodeficiency virus (HIV) infection in children can be complicated by the development of cardiac disease. Decreased left ventricular function has been temporally associated with the use of zidovudine (azidothymidine; AZT) in adults with HIV and has been associated with changes in cardiac muscle mitochondria in animal models. This study was done in an attempt to determine whether the cardiac disease is related to the antiretroviral therapy or to progressive HIV infection, Methods: We retrospectively reviewed echocardiograms, clinical records, and laboratory data from 137 HIV-infected children who were being treated by the Pediatric Branch, National Cancer Institute, and who were receiving AZT or didanosine, both drugs, or no antiretroviral therapy, Results: Despite correction of the echocardiographic results for HIV disease severity with markers such as CD4(+) lymphocyte count, time since infection, mode of acquisition of HIV, and age, children who were treated with AZT had a lower average fractional shortening than those who were not treated with APT (p < 0.0001), There was a nonlinear relation between days of AZT use and this decrease in fractional shortening. The odds that a cardiomyopathy would develop was 8.4 times greater in children who had previously used AZT than in those who had never taken AZT (95% confidence interval, 1.7 to 42.0). Didanosine was not associated with the development of a cardiomyopathy. Conclusions: Treatment of HIV-infected children with AZT may be associated with the development of a cardiomyopathy; didanosine does not appear to increase the risk of cardiomyopathy. The continued use of APT in a child in whom a cardiomyopathy develops should be carefully assessed, and all children receiving APT should be followed by serial cardiac examination and echocardiograms. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. GEORGETOWN UNIV HOSP, DIV CARDIOL, WASHINGTON, DC 20007 USA. NHLBI, BIOSTAT RES BRANCH, BETHESDA, MD 20892 USA. RP DOMANSKI, MJ (reprint author), NHLBI, CARDIOL BRANCH, CLIN TRIALS BRANCH, CLIN TRIALS GRP, ROOM 5C10, BETHESDA, MD 20892 USA. NR 22 TC 80 Z9 82 U1 0 U2 0 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 JUL PY 1995 VL 127 IS 1 BP 137 EP 146 DI 10.1016/S0022-3476(95)70275-X PG 10 WC Pediatrics SC Pediatrics GA RH637 UT WOS:A1995RH63700026 PM 7608800 ER PT J AU ROTHMAN, RB SILVERTHORN, ML BAUMANN, MH GOODMAN, CB CADET, JL MATECKA, D RICE, KC CARROLL, FI WANG, JB UHL, GR PARTILLA, JS DERSCH, CM AF ROTHMAN, RB SILVERTHORN, ML BAUMANN, MH GOODMAN, CB CADET, JL MATECKA, D RICE, KC CARROLL, FI WANG, JB UHL, GR PARTILLA, JS DERSCH, CM TI STUDIES OF THE BIOGENIC-AMINE TRANSPORTERS .6. CHARACTERIZATION OF A NOVEL COCAINE BINDING-SITE, IDENTIFIED WITH [I-125] RTI-55, IN MEMBRANES PREPARED FROM WHOLE RAT-BRAIN MINUS CAUDATE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIGH-AFFINITY BINDING; DOPAMINE TRANSPORTER; LIGAND-BINDING; NEUROTRANSMITTER TRANSPORTER; SEROTONIN TRANSPORTERS; I-125 RTI-55; H-3 COCAINE; MOUSE-BRAIN; NOREPINEPHRINE; STRIATUM AB Previous studies showed that the cocaine analog [(1)25I]RTI-55 labels dopamine and serotonergic (5-HT) biogenic amine transporters (BATs) with high affinity. Here we characterized [I-125]RTI-55 binding to membranes prepared from whole rat brain minus the caudate nuclei. Paroxetine (50 nM) was used to block [I-125]RTI-55 binding to 5-HT transporter sites. Initial experiments identified drugs that displaced [I-125]RTI-55 binding with moderately low slope factors. Binding surface analysis of the interaction of 3 beta-(4-chlorophenyl)tropan-2 beta-carboxylic acid phenyl ester hydrochloride (RTI-113) and 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid phenyl ester hydrochloride (RTI-122) with [I-125]RTI-55 binding sites readily resolved two binding sites for [I-125]RTI-55 with K-d values of 0.44 nM and 17 nM and B-max values of 31 and 245 fmol/mg protein. Potent 5-HT and noradrenergic uptake inhibitors had low affinity for both sites. Whereas cocaine, CFT and WIN35,065-2 were 6.0-, 25- and 14-fold selective for the first site, benztropine, PCP and the novel pyrrole, (I)-(2RS,3aSR,8bRS)-1,2,3,3a,4,8b-hexahydro-2-benzyl-1-methylindeno-[1,2-b]pyrrole resorcylate [(+/-)HBMP, formerly called (+/-)-RTI-4793-14], were moderately selective for the second site. A single binding site with the characteristics of site 1 was resolved using COS cells transiently expressing the cloned rat dopamine transporter. Lesion stud ies with 6-hydroxydopamine and 5,7-dihydroxytryptamine were conducted to test the hypothesis that site 1 and site 2 are physically distinct. The data showed that these neurotoxins differentially decreased [I-125]RTI-55 binding to sites 1 and 2. The differential distribution of sites 1 and 2 in rat brain provides further support for this hypothesis. Viewed collectively, these data show that [I-125]RTI-55 labels a novel binding site in rat brain membranes, termed DAT(site2), which is not associated with the classic dopamine, serotonin or norepinephrine transporters. C1 NIDA,DIV INTRAMURAL RES,CLIN PHARMACOL SECT,BALTIMORE,MD. NIDA,DIV INTRAMURAL RES,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD. NIDA,DIV INTRAMURAL RES,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 50 TC 11 Z9 11 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 JUL PY 1995 VL 274 IS 1 BP 385 EP 395 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RJ364 UT WOS:A1995RJ36400053 PM 7616423 ER PT J AU DILISA, F BLANK, PS COLONNA, R GAMBASSI, G SILVERMAN, HS STERN, MD HANSFORD, RG AF DILISA, F BLANK, PS COLONNA, R GAMBASSI, G SILVERMAN, HS STERN, MD HANSFORD, RG TI MITOCHONDRIAL-MEMBRANE POTENTIAL IN SINGLE LIVING ADULT-RAT CARDIAC MYOCYTES EXPOSED TO ANOXIA OR METABOLIC INHIBITION SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HEART MYOCYTES; COMPLEX-I; ATP; CALCIUM; MUSCLE; INJURY; CELLS; PORE; COMPARTMENTATION; REOXYGENATION AB The relation between mitochondrial membrane potential (Delta Psi(m)) and cell function was investigated in single adult rat cardiac myocytes during anoxia and reoxygenation. Delta Psi(m) was studied by loading myocytes with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetra-ethylbenzimidazolylcarbocyanine iodide), a fluorescent probe characterized by two emission peaks (539 and 597 nm with excitation at 490 nm) corresponding to monomer and aggregate forms of the dye. 2. De-energizing conditions applied to mitochondria, cell suspensions or single cells decreased the aggregate emission and increased the monomer emission. This latter result cannot be explained by changes of JC-1. concentration in the aqueous mitochondrial matrix phase indicating that hydrophobic interaction of the probe with membranes has to be taken into account to explain JC-1. fluorescence properties in isolated mitochondria or intact cells. 3. A different sensitivity of the two JC-1 forms to Delta Psi(m) changes was shown in isolated mitochondria by the effects of ADP and FCCP and the calibration with K+ diffusion potentials. The monomer emission was responsive to values of Delta Psi(m) below 140 mV, which hardly modified the aggregate emission. Thus JC-1 represents a unique double sensor which can provide semi-quantitative information in both low and high potential ranges. 4. At the onset of glucose-free anoxia the epifluorescence of individual myocytes studied in the single excitation (490 nm)-double emission (530 and 590 nm) mode showed a gradual decline of the aggregate emission, which reached a plateau while electrically stimulated (0.2 Hz) contraction was still retained. The subsequent failure of contraction was followed by the rise of the emission at 530 nm, corresponding to the monomer form of the dye, concomitantly with the development of rigor contracture. 5. The onset of the rigor was preceded by the increase in intracellular Mg2+ concentration ([Mg2+](1)) monitored by mag-indo-1 epifluorescence. Since under these experimental conditions intracellular [Ca2+] and pH are fairly stable, the increase in [Mg2+](i) was likely to be produced by a decrease in ATP content. 6. The inhibition of mitochondrial ATPase induced by oligomycin during anoxia was associated with a rapid and simultaneous change of both the components of JC-l fluorescence, suggesting that Delta Psi(m) instead of producing ATP, is generated by glycolytic ATP during anoxia. 7. The readmission of oxygen induced a rapid decrease of the monomer emission and a slower increase of the aggregate emission. These fluorescence changes were not necessarily associated with the recovery of mechanical function. Even in those cells which hypercontracted during reoxygenation a further addition of FCCP induced a decrease in Delta Psi(m) and an increase in [Mg2+](1), indicating that residual mitochondrial function and ATP production can exist even in irreversibly damaged cells. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. UNIV PADUA,DIPARTIMENTO SCI BIOMED,PADUA,ITALY. NR 38 TC 192 Z9 198 U1 0 U2 5 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 JUL 1 PY 1995 VL 486 IS 1 BP 1 EP 13 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA RJ037 UT WOS:A1995RJ03700001 PM 7562625 ER PT J AU SNEESBY, TA MEIERS, JC AF SNEESBY, TA MEIERS, JC TI INFLUENCE OF SALIVA CONTAMINATION AND ABRASION ON RESIN TO TIN-PLATED ALLOY BOND STRENGTHS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID RETAINERS AB This investigation studied the effects of abrasion and salivary contamination on the shear bond strength of a composite resin bonded to tin-plated gold alloy. Experimental groups (n = 15) consisted of: group 1, no surface treatment; group 2, enamel abraded; and group 3, saliva-contaminated. After surface stressing and bonding, groups were thermocycled before shear testing. Fractured interfaces were analyzed by use of light microscopy and SEM. Specimens in group 3 (12.2 +/- 2.5 MPa) had significantly lower bond strengths than group 1 (17.9 +/- 6.8 MPa). The shear bond strengths of resin bonded to tin-plated metal were significantly affected by salivary contamination but not by abrasion. C1 USN,SCH DENT,RES DEPT,BETHESDA,MD 20889. NIDR,RES DEPT,BETHESDA,MD. NR 16 TC 3 Z9 3 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 JUL PY 1995 VL 74 IS 1 BP 100 EP 105 DI 10.1016/S0022-3913(05)80232-X PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RG141 UT WOS:A1995RG14100012 PM 7674179 ER PT J AU VIRKKUNEN, M GOLDMAN, D NIELSEN, DA LINNOILA, M AF VIRKKUNEN, M GOLDMAN, D NIELSEN, DA LINNOILA, M TI LOW BRAIN-SEROTONIN TURNOVER RATE (LOW CSF 5-HIAA) AND IMPULSIVE VIOLENCE SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article DE BRAIN SEROTONIN; IMPULSIVE VIOLENCE; HYPOGLYCEMIC TENDENCY; ACTIVITY RHYTHMS; VAGAL TONE; D2 RECEPTOR GENOTYPE; TRYPTOPHAN HYDROXYLASE GENE ID FLUID 5-HYDROXYINDOLEACETIC ACID; DOPAMINE RECEPTOR GENE; CEREBROSPINAL-FLUID; DISRUPTIVE BEHAVIOR; AUTONOMIC MEASURES; HOMOVANILLIC-ACID; FIRE SETTERS; VAGAL TONE; ALCOHOLISM; ASSOCIATION AB The findings of a series of studies by the authors support the idea that most impulsive offenders who have a tendency to behave aggressively while intoxicated have a low brain serotonin turnover rate. The impulsive violent offenders with the lowest CSF 5-HIAA concentrations have diurnal activity rhythm disturbances, and are also prone to hypoglycemia after an oral glucose challenge. Low CSF 5-HIAA combined with hyoglycemic tendency also predicts future violence under the influence of alcohol. Sons of alcoholic fathers, who have committed violent crimes, have very low CSF 5-HIAA concentrations. Vagal tone does not correlate significantly with CSF 5-HIAA but correlates with enhanced insulin secretion, which is most prominent in subjects with intermittent explosive disorder. A polymorphism of tryptophan hydroxylase (TPH) gene is associated with low CSF 5-HIAA and a history of suicide attempts. C1 NIAA,DICBR,LNG,MOLEC GENET SECT,BETHESDA,MD. UNIV HELSINKI,DEPT PSYCHIAT,SF-00100 HELSINKI 10,FINLAND. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 34 TC 149 Z9 152 U1 0 U2 8 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatr. Neurosci. PD JUL PY 1995 VL 20 IS 4 BP 271 EP 275 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RH227 UT WOS:A1995RH22700003 PM 7544158 ER PT J AU FARAGGI, D SIMON, R AF FARAGGI, D SIMON, R TI THE MAXIMUM-LIKELIHOOD NEURAL - NETWORK AS A STATISTICAL CLASSIFICATION MODEL SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE CLASSIFICATION; FEEDFORWARD NEURAL NETWORKS; LOGISTIC LIKELIHOOD; MAXIMUM LIKELIHOOD AB Neural networks have received considerable attention in recent years. This development has been pursued primarily by non-statisticians. Consequently many statistical tools and concepts have not been utilized in this development and great claims for neural networks have sometimes been made without comparisons to standard statistical procedures. In this paper we utilize the input-output relationship associated with a simple feed-forward neural network as the basis for a non-linear multivariate classifier. A statistical model for the data is defined based on a logistic likelihood function. Neural network parameters are estimated using the method of maximum likelihood instead of the back-propagation technique often used in the neural network literature. An extension for the multinomial case is presented. These maximum likelihood based models can be compared using readily available techniques such as the likelihood ratio test and the Akaike criterion (1973). We provide empirical comparisons of this network approach with standard logistic regression for both the binomial and multinomial cases. C1 NATL CANC INST,BIOMETR RES BRANCH,ROCKVILLE,MD 20852. NR 28 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL PY 1995 VL 46 IS 1 BP 93 EP 104 DI 10.1016/0378-3758(95)99068-2 PG 12 WC Statistics & Probability SC Mathematics GA RE194 UT WOS:A1995RE19400006 ER PT J AU DOW, SP SONIES, BC SCHEIB, D MOSS, SE LEONARD, HL AF DOW, SP SONIES, BC SCHEIB, D MOSS, SE LEONARD, HL TI PRACTICAL GUIDELINES FOR THE ASSESSMENT AND TREATMENT OF SELECTIVE MUTISM SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE SELECTIVE (OR ELECTIVE) MUTISM; CHILD; ANXIETY DISORDERS; SOCIAL PHOBIA; PHARMACOTHERAPY; SPEECH AND LANGUAGE ID ELECTIVE MUTISM; RIGHT-HEMISPHERE; CHILDREN AB Objective: To provide practical guidelines for the assessment and treatment of children with selective mutism, in light of the recent hypothesis that selective mutism might be best conceptualized as a childhood anxiety disorder. Method: An extensive literature review was completed on the phenomenology, evaluation, and treatment of children with selective mutism. Additional recommendations were based on clinical experience from the authors' selective mutism clinic. Results: No systematic studies of the phenomenology of children with selective mutism were found. Reports described diverse and primarily noncontrolled treatment approaches with minimal follow-up information. Assessment and treatment options for selective mutism are presented, based on new hypotheses that focus on the anxiety component of this disorder. Ongoing research suggests a role for behavior modification and pharmacotherapy similar to the approaches used for adults with social phobia. Conclusion: Selectively mute children deserve a comprehensive evaluation to identity primary and comorbid problems that might require treatment. A school-based multidisciplinary individualized treatment plan is recommended, involving the combined effort of teachers, clinicians, and parents with home- and clinic-based interventions (individual and family psychotherapy, pharmacotherapy) as required. C1 NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT REHABIL MED,SPEECH LANGUAGE & PATHOL SECT,BETHESDA,MD 20892. NR 68 TC 60 Z9 61 U1 1 U2 17 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 JUL PY 1995 VL 34 IS 7 BP 836 EP 846 DI 10.1097/00004583-199507000-00006 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100006 PM 7649953 ER PT J AU BLACK, B UHDE, TW AF BLACK, B UHDE, TW TI PSYCHIATRIC CHARACTERISTICS OF CHILDREN WITH SELECTIVE MUTISM - A PILOT-STUDY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE SELECTIVE MUTISM; ANXIETY; SOCIAL PHOBIA; FAMILY HISTORY ID ELECTIVE MUTISM; SOCIAL PHOBIA; MODIFIED CONNERS; DISORDERS; ANXIETY; PREVALENCE; MOOD AB Objective: To ascertain characteristics of children with selective mutism. Method: Subjects with selective mutism were evaluated by means of parent and teacher rating scales and structured diagnostic interviews. Results: Thirty children were evaluated. Mutism severity varied markedly in different environmental settings. Ninety-seven percent of the subjects were diagnosed with social phobia or avoidant disorder of childhood or adolescence or both and 30% with simple phobia. No other psychiatric disorders were common. Parent and teacher rating scales showed high levels of anxiety symptoms, especially social anxiety, and low levels of all other psychiatric symptoms. Anxiety and social anxiety severity correlated with mutism severity. First-degree family history of social phobia and of selective mutism, obtained by family history method, was present in 70% and 37% of families, respectively. There was no evidence of a causal relationship between psychologically or physically traumatic experiences and development of selective mutism. Conclusions: Selective mutism may be a symptom of social anxiety, rather than a distinct diagnostic syndrome. Further study of the characteristics of children with selective mutism and their families is warranted. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT,DETROIT,MI 48201. NIMH,BETHESDA,MD 20892. RP BLACK, B (reprint author), NEW ENGLAND MED CTR 1007,750 WASHINGTON ST,BOSTON,MA 02111, USA. NR 31 TC 125 Z9 125 U1 9 U2 39 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 JUL PY 1995 VL 34 IS 7 BP 847 EP 856 DI 10.1097/00004583-199507000-00007 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100007 PM 7649954 ER PT J AU ARNOLD, LE STOFF, DM COOK, E COHEN, DJ KRUESI, M WRIGHT, C HATTAB, J GRAHAM, P ZAMETKIN, A CASTELLANOS, FX MCMAHON, W LECKMAN, JF AF ARNOLD, LE STOFF, DM COOK, E COHEN, DJ KRUESI, M WRIGHT, C HATTAB, J GRAHAM, P ZAMETKIN, A CASTELLANOS, FX MCMAHON, W LECKMAN, JF TI ETHICAL ISSUES IN BIOLOGICAL PSYCHIATRIC RESEARCH WITH CHILDREN AND ADOLESCENTS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ETHICS; RESEARCH; RISK; CONSENT ID CONSENT; BLOOD AB Objective: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. Method: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. Results: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, ''piggybacking'' onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; ''coercive'' inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. Conclusions: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects. C1 NIMH,MOOD ANXIETY & PERSONAL DISODERS RES BRANCH,ROCKVILLE,MD 20857. UNIV CHICAGO,CHICAGO,IL 60637. YALE UNIV,SCH MED,YALE CHILD STUDY CTR,NEW HAVEN,CT. UNIV ILLINOIS,CHICAGO,IL 60680. COLUMBIA UNIV,NEW YORK,NY 10027. HADASSAH MED SCH,EITANIM HOSP,MH CTR,JERUSALEM,ISRAEL. UNIV LONDON,INST CHILD HLTH,LONDON WC1N 1EH,ENGLAND. NIMH,CHILD PSYCHIAT BRANCH,ROCKVILLE,MD 20857. UNIV UTAH,DIV CHILD PSYCHIAT,SALT LAKE CITY,UT 84112. RP ARNOLD, LE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 38 TC 38 Z9 38 U1 0 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 JUL PY 1995 VL 34 IS 7 BP 929 EP 939 DI 10.1097/00004583-199507000-00017 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100017 PM 7649964 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI RESOLVED - MULTIPLE PERSONALITY-DISORDER IS AN INDIVIDUALLY AND SOCIALLY CREATED ARTIFACT - NEGATIVE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Discussion ID CLINICAL PHENOMENOLOGY RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 2 U2 3 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 JUL PY 1995 VL 34 IS 7 BP 960 EP 962 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100022 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI RESOLVED - MULTIPLE PERSONALITY-DISORDER IS AN INDIVIDUALLY AND SOCIALLY CREATED ARTIFACT - NEGATIVE REBUTTAL SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Discussion RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 1995 VL 34 IS 7 BP 963 EP 963 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100024 ER PT J AU GIDDING, SS XIE, XY LIU, KA MANOLIO, T FLACK, JM GARDIN, JM AF GIDDING, SS XIE, XY LIU, KA MANOLIO, T FLACK, JM GARDIN, JM TI CARDIAC-FUNCTION IN SMOKERS AND NONSMOKERS - THE CARDIA STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CIGARETTE-SMOKING; DOPPLER ECHOCARDIOGRAPHY; PULMONARY-ARTERY; BLOOD-PRESSURE; YOUNG-ADULTS; EXERCISE; FLOW AB Objectives. This study assessed clinical and echocardiographic measures of cardiac function at rest in smokers and nonsmokers to determine the associations of cigarette smoking with various measures of left and right ventricular performance. Background. Whereas the immediate cardiovascular effects of cigarette smoking have been well described, the long-term effects in an otherwise healthy cohort have not. Of particular interest were associations with heart rate, left ventricular end systolic stress and left ventricular mass because higher levels of these measures would suggest increased myocardial oxygen consumption. Methods. In year 5 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3,366 smokers and nonsmokers (ex-smokers were excluded) underwent echocardiography as well as assessment of heart rate, anthropometric measurements and blood pressure. Participants ranged in age from 23 to 35 years and were equally distributed by race and gender, Echocardiographic measures included pulsed Doppler pulmonary artery acceleration time (a decrease suggests increased pulmonary artery pressure), left ventricular mass, left ventricular end-systolic stress and left ventricular fractional shortening. Results. All comparisons were between smokers and nonsmokers. Heart rate at rest was significantly higher in smokers by 1.5 to 5 beats/min in all race/gender groups except black men. In men who smoked, pulmonary artery acceleration time was significantly lower by 4 to 8 ms, Except for black male smokers, there was a trend toward increased left ventricular mass (3 to 8 g) in all race/gender groups, significant in black women. Left ventricular end-systolic stress was significantly higher in women who smoked (4 to 6 dynes/cm(2)). There were no differences for systolic blood pressure or left ventricular fractional shortening. Conclusion. In an assessment of cardiovascular function at rest in young adults, quantifiable differences between smokers and nonsmokers that predict increased rest myocardial oxygen consumption in smokers were found. Some of these differences were gender specific. C1 NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL. NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHICAGO,IL. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT INTERNAL MED,MINNEAPOLIS,MN 55455. UNIV CALIF IRVINE,DEPT INTERNAL MED,ORANGE,CA 92668. FU NHLBI NIH HHS [N01-HC 48048, N01-HC 48047, N01-HC 48049] NR 30 TC 36 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1995 VL 26 IS 1 BP 211 EP 216 DI 10.1016/0735-1097(95)00118-J PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RG110 UT WOS:A1995RG11000029 PM 7797754 ER PT J AU SHIP, JA GRUSHKA, M LIPTON, JA MOTT, AE SESSLE, BJ DIONNE, RA AF SHIP, JA GRUSHKA, M LIPTON, JA MOTT, AE SESSLE, BJ DIONNE, RA TI BURNING MOUTH SYNDROME - AN UPDATE SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID SALIVARY FLOW-RATE; CHRONIC PAIN; REPLACEMENT THERAPY; ORAL DISCOMFORT; FACIAL-PAIN; MANAGEMENT; AMITRIPTYLINE; COMPLAINTS; ANTIDEPRESSANTS; PREVALENCE AB Though it has been the subject of much research, burning mouth syndrome-a chronic oral-facial pain condition that affects many U.S. adults-remains poorly understood. It has been associated with numerous oral and systemic conditions. Treatment options frequently include various medications. While patients with symptoms of BMS are more likely to seek care from physicians, dentists should be involved in the evaluation and management of these patients. C1 UNIV TORONTO,FAC DENT,TORONTO,ON,CANADA. NIDR,DIV EXTRAMURAL RES,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,CTR TASTE & SMELL,FARMINGTON,CT. UNIV TORONTO,FAC DENT,TORONTO,ON,CANADA. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,CLIN PHARMACOL UNIT,BETHESDA,MD 20892. RP SHIP, JA (reprint author), UNIV MICHIGAN,HOSP DENT,SCH DENT,1011 N UNIV,ROOM 2010,ANN ARBOR,MI 48109, USA. NR 65 TC 78 Z9 87 U1 0 U2 2 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 JUL PY 1995 VL 126 IS 7 BP 842 EP 853 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RJ367 UT WOS:A1995RJ36700011 PM 7629360 ER PT J AU STRECKFUS, CF AF STRECKFUS, CF TI SALIVARY FUNCTION AND HYPERTENSION - A REVIEW OF THE LITERATURE AND A CASE-REPORT SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID FLOW-RATE; MOUTH; PH AB Limited evidence suggests a relationship between the use of antihypertensive medications and reduced salivary function. This article provides a review of the literature concerning the relationship between hypertension, hypertensive therapy and salivary function. A case report is presented to illustrate changes in salivary function in response to different types of antihypertensive medications. C1 NIDR,EPIDEMIOL ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. NR 37 TC 21 Z9 24 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 JUL PY 1995 VL 126 IS 7 BP 1012 EP 1017 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RJ367 UT WOS:A1995RJ36700015 PM 7629342 ER PT J AU SUBAR, AF THOMPSON, FE SMITH, AF JOBE, JB ZIEGLER, RG POTISCHMAN, N SCHATZKIN, A HARTMAN, A SWANSON, C KRUSE, L HAYES, RB LEWIS, DR HARLAN, LC AF SUBAR, AF THOMPSON, FE SMITH, AF JOBE, JB ZIEGLER, RG POTISCHMAN, N SCHATZKIN, A HARTMAN, A SWANSON, C KRUSE, L HAYES, RB LEWIS, DR HARLAN, LC TI IMPROVING FOOD FREQUENCY QUESTIONNAIRES - A QUALITATIVE APPROACH USING COGNITIVE INTERVIEWING SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY; VALIDATION; REPRODUCIBILITY; CONSUMPTION; LIMITATIONS; VALIDITY; HISTORY; RECORDS AB In an attempt to improve data quality and ease of administration of standard self-administered food frequency questionnaires, various alternative approaches were tried for inquiring about frequency of consumption, portion size, seasonal intake, and food preparation. Evaluation consisted of a cognitive interviewing method in which respondents verbalize their thought process while completing several variations of a questionnaire. Interviewers observed and asked follow-up probe questions to evaluate problems or inconsistencies verbalized by respondents. Consensus and judgment by interviewers and observers suggested several problematic features of food frequency questionnaires: formatting of questions about frequency and portion size; computing average frequencies for aggregated food items or for foods eaten seasonally; comprehension of many items; and ordering of foods. These findings led to cognitive refinement and innovations, which included detailed questions regarding preparation or use of low-fat varieties or other alternatives to help better describe specifics of intake for some foods; questions on seasonal intake for several foods; inclusion of portion size ranges; and additional response categories for frequency of intake. Cognitive interviewing is an important step in pinpointing cognitive problems in dietary questionnaires. C1 SUNY BINGHAMTON,DEPT PSYCHOL,BINGHAMTON,NY. NATL CTR HLTH STAT,OFF RES & METHODOL,HYATTSVILLE,MD 20782. NOVA RES CO,BETHESDA,MD. RP SUBAR, AF (reprint author), NCI,DIV CANC PREVENT & CONTROL,EPN 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 35 TC 126 Z9 129 U1 1 U2 8 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1995 VL 95 IS 7 BP 781 EP 788 DI 10.1016/S0002-8223(95)00217-0 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RG262 UT WOS:A1995RG26200013 PM 7797809 ER PT J AU FOLEY, DJ WALLACE, RB EBERHARD, J AF FOLEY, DJ WALLACE, RB EBERHARD, J TI RISK-FACTORS FOR MOTOR-VEHICLE CRASHES AMONG OLDER DRIVERS IN A RURAL-COMMUNITY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ESTABLISHED POPULATIONS; DRIVING CESSATION; FREE-RECALL; AGE AB OBJECTIVE: To estimate the motor vehicle crash rate in a cohort of older drivers from a rural community and to identify health-related conditions that increase their risk for crash involvement. DESIGN: Cohort study with 5 years of crash-record surveillance. SETTING: The Iowa 65+ Rural Health Study, one of four Established Populations for Epidemiologic Studies of the Elderly (EPESE). PARTICIPANTS: A total of 1791 drivers aged 68 years and older. MAIN MEASURES: Exposure measures of physical, mental, and sensory well-being from a health interview survey; outcome measure of police-reported crashes maintained by the Iowa Department of Motor Vehicles. RESULTS: Between 1985 and 1989, 206 drivers were involved in 245 state-recorded crashes. The estimated annual crash involvement rate for these rural older drivers (28 per 1000 driving-years) was about 20% less than the national average for drivers aged 65 years and over (36 per 1,000). An increased risk for motor vehicle crashes was associated with episodes of back pain (Relative Risk = 1.4, P < .05), use of nonsteroidal anti-inflammatory drugs (RR = 1.7, P < .01), and poor performance on a free-recall memory test (RR = 1.4, P < .05). CONCLUSIONS: If these and other geriatric conditions are confirmed as risk factors for motor vehicle crashes, medical guidelines for license renewal may need updating and health professionals may need new instruments to detect older patients at high risk for unsafe driving. C1 UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. NATL HIGHWAY TRAFF SAFETY ADM,OFF DRIVER EVALUAT & RES,WASHINGTON,DC 20590. RP FOLEY, DJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,RM 3C-309,BETHESDA GATEWAY BLDG,7201 WISCONSIN AV,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02106] NR 30 TC 61 Z9 62 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1995 VL 43 IS 7 BP 776 EP 781 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RH100 UT WOS:A1995RH10000009 PM 7602030 ER PT J AU GLOTH, FM TOBIN, JD AF GLOTH, FM TOBIN, JD TI VITAMIN-D DEFICIENCY IN OLDER-PEOPLE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review ID RAT OSTEOCALCIN GENE; OSTEO-SARCOMA CELLS; D-BINDING PROTEIN; 1,25-DIHYDROXYVITAMIN D3; PARATHYROID-HORMONE; NUTRITIONAL-STATUS; D SUPPLEMENTATION; ELDERLY PEOPLE; SERUM LEVELS; SECONDARY HYPERPARATHYROIDISM C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP GLOTH, FM (reprint author), UNION MEM HOSP,DIV GERIATR,201 E UNIV PKWY,BALTIMORE,MD 21218, USA. NR 98 TC 79 Z9 80 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1995 VL 43 IS 7 BP 822 EP 828 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RH100 UT WOS:A1995RH10000019 PM 7602040 ER PT J AU TEIGEN, PM AF TEIGEN, PM TI SORE ARMS AND SELECTIVE MEMORIES - LEUF,ALEXANDER,H.P. AND THE BEGINNING OF BASEBALL MEDICINE SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Article RP TEIGEN, PM (reprint author), NATL LIB MED,DIV HIST MED,BETHESDA,MD 20894, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU J HIST MED ALLIED SCI INC PI CANTON PA PO BOX 487, CANTON, MA 02021 SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JUL PY 1995 VL 50 IS 3 BP 391 EP 408 DI 10.1093/jhmas/50.3.391 PG 18 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA RN056 UT WOS:A1995RN05600004 PM 7665878 ER PT J AU TAMURA, K JONES, M YAMADA, I FERRANS, VJ AF TAMURA, K JONES, M YAMADA, I FERRANS, VJ TI A COMPARISON OF FAILURE MODES OF GLUTARALDEHYDE-TREATED VERSUS ANTIBIOTIC-PRESERVED MITRAL-VALVE ALLOGRAFTS IMPLANTED IN SHEEP SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID AORTIC-VALVE; CARDIAC VALVES; REPLACEMENT; HOMOGRAFTS; XENOGRAFTS AB Morphologic studies and calcium analyses were made on mitral valve allografts from 12 juvenile sheep surviving 12 to 24 weeks after mitral valve replacement. Before implantation, the allografts were treated with 0.625% glutaraldehyde (group I, n = 4) or with cold antibiotic solution (group II, n = 8). Three group I animals died 12 to 19 weeks after implantation because of dysfunction of calcified valves; the surviving animal also had extensive allograft calcification. One group II animal died of mitral regurgitation; the valves of the other seven (including five with regurgitation shown by Doppler and ventriculographic studies) were explanted at 19 to 24 weeks. Chordal rupture related to calcific deposits was found in all group I valves. Leaflet perforations (n = 4) and ruptured chordae (n = 4), each caused by connective tissue deterioration, were found in group II valves. Inflammatory reaction was absent or minimal in group I valves but moderate or severe in group II valves. Fibrous sheaths were thicker in group I than in group I valves. Calcium levels were much higher in group I than in group II valves. Calcification in group I valves was diffuse and involved collagen, elastic fibers, and connective tissue cells and matrix; in group II valves, it was localized in connective tissue cells, Thus glutaraldehyde-treated allografts failed because of extensive calcification, whereas antibiotic-preserved allografts underwent deterioration of connective tissue and infiltration by inflammatory cells. C1 NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BETHESDA,MD 20892. NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. NR 40 TC 46 Z9 50 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 1995 VL 110 IS 1 BP 224 EP 238 DI 10.1016/S0022-5223(05)80029-7 PG 15 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA RJ114 UT WOS:A1995RJ11400028 PM 7609546 ER PT J AU WALTHER, MM ANGLARD, P GNARRA, J POZZATTI, R VENZON, D DELAROSA, A MACDONALD, NJ STEEG, PS LINEHAN, WM AF WALTHER, MM ANGLARD, P GNARRA, J POZZATTI, R VENZON, D DELAROSA, A MACDONALD, NJ STEEG, PS LINEHAN, WM TI EXPRESSION OF NM23 IN CELL-LINES DERIVED FROM PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA, RENAL CELL; GENES, TUMOR SUPPRESSOR ID NUCLEOSIDE DIPHOSPHATE KINASE; IMMUNOHISTOCHEMICAL ANALYSIS; COLORECTAL CARCINOMAS; REDUCED EXPRESSION; DISTANT METASTASES; PROTEIN EXPRESSION; TUMOR-METASTASIS; MESSENGER-RNA; GENE; CANCER AB Reduced expression of nm23 has been associated with increased metastases and decreased survival in a variety of malignancies. In the present study, the expression of nm23 was examined by Northern and Western blot analyses in a series of cell lines derived from patients with metastatic renal cell carcinoma. Two of twelve (17%) informative cell Lines derived from 9 patients had loss of heterozygosity at Nm23-H1. Twenty-two renal cancer cell Lines derived from primary tumors, 5 cell lines derived from metastatic tumors and 4 short-term cultures of normal proximal renal tubular cells all expressed Nm23 mRNA in varying amounts. On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines. Twenty-eight cell lines derived from renal primary tumors and 8 cell Lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins. High or low relative expression of nm23 at the mRNA or protein level did not correlate with survival. The absence of any anomalous pattern of expression of the nm23 genes and the lack of correlation of expression with survival suggests that nm23 does not play a central role in the progression of this tumor type. C1 NCI,WOMENS CANC SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOSTAT SECT,BETHESDA,MD 20892. NCI,DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP WALTHER, MM (reprint author), NCI,SURG BRANCH,UROL ONCOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B-43,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 47 TC 13 Z9 14 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 JUL PY 1995 VL 154 IS 1 BP 278 EP 282 DI 10.1016/S0022-5347(01)67294-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA RB819 UT WOS:A1995RB81900088 PM 7776445 ER PT J AU VANDENDRIESSCHE, T CHUAH, MKL CHIANG, L CHANG, HK ENSOLI, B MORGAN, RA AF VANDENDRIESSCHE, T CHUAH, MKL CHIANG, L CHANG, HK ENSOLI, B MORGAN, RA TI INHIBITION OF CLINICAL HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 ISOLATES IN PRIMARY CD4(+) T-LYMPHOCYTES BY RETROVIRAL VECTORS EXPRESSING ANTI-HIV GENES SO JOURNAL OF VIROLOGY LA English DT Article ID HAIRPIN RIBOZYME; TRANS-ACTIVATOR; REPLICATION; PROTEIN; CELLS; TAT; REV; SEQUENCES; RNA; OVEREXPRESSION AB Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4(+) T lymphocytes. We therefore transduced CD4(+) T lymphocytes from uninfected individuals with retroviral vectors expressing either HIV-1-specific antisense-TAR or antisense-Tat/Rev RNA, transdominant HIV-1 Rev protein, and a combination of antisense-TAR and transdominant Rev. The engineered CD4(+) T lymphocytes were then infected with four different clinical HIV-1 isolates. We found that replication of all HIV-1 isolates was inhibited by all the anti-HIV vectors tested. Greater inhibition of HIV-1 was observed with transdominant Rev than,vith antisense RNA. We hereby demonstrated effective protection by antisense RNA or transdominant mutant proteins against HIV-1 infection in primary CD4(+) T lymphocytes using clinical HIV-1 isolates, and this represents an essential step toward clinical anti-HIV-1 gene therapy. C1 NATL CTR HUMAN GENOME RES, CLIN GENE THERAPY BRANCH, GENE TRANSFER TECHNOL SECT, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD 20878 USA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 58 TC 74 Z9 74 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 JUL PY 1995 VL 69 IS 7 BP 4045 EP 4052 PG 8 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600012 PM 7769662 ER PT J AU HUANG, M TAKAC, M KOZAK, CA JOLICOEUR, P AF HUANG, M TAKAC, M KOZAK, CA JOLICOEUR, P TI THE MURINE AIDS DEFECTIVE PROVIRUS ACTS AS AN INSERTIONAL MUTAGEN IN ITS INFECTED TARGET B-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; PUTATIVE ONCOGENE SPI-1; VIRUS-INDUCED LYMPHOMA; LEUKEMIA-VIRUS; TRANSCRIPTION FACTOR; MOUSE CHROMOSOME-11; INTEGRATION SITE; FRIEND-ERYTHROLEUKEMIA; COOPERATING ONCOGENES; DNA AB In susceptible mice, the murine AIDS (MAIDS) defective virus can induce marked expansion of its target cells, the majority of which belong to the B-cell lineage. This expansion, which appears to be critical for the development of the immunodeficiency syndrome, is initially polyclonal but becomes oligoclonal late in the disease, suggesting the involvement of a secondary genetic event(s) during this proliferation. To determine whether integration of the MAIDS defective provirus into particular regions of the cellular genome contributes to this oligoclonal expansion, we searched for common provirus integration sites in enlarged lymphoid organs of MAIDS mice. We identified two common proviral integration sites, Dis-1 and Dis-2, which were occupied by a defective provirus at frequencies of 20 and 13%, respectively. Our analysis revealed that the Dis-1 region corresponds to the Sfpi1 (Spi-1, PU.1) locus, which maps on chromosome 2, and encodes a transcription factor. Insertion of the MAIDS defective provirus into this region led to a two- to threefold increase in the expression of Sfpi1 RNA. The Dis-2 locus was found to map to mouse chromosome 11, between Hox2 and Scya. It appears to be a novel locus probably harboring a gene involved in B-cell proliferation. The present study indicates that the MAIDS defective provirus can act as an insertional mutagen, thus contributing to the oligoclonal expansion of infected cells. The detection of two common proviral integration sites, each of which targetted at a low frequency in diseased organs, suggests that the deregulation of a unique gene through provirus insertion is essential for neither proliferation of infected B cells nor development of the immunodeficiency syndrome. C1 CLIN RES INST MONTREAL,MOLEC BIOL LAB,MONTREAL,PQ H2W 1R7,CANADA. UNIV MONTREAL,DEPT IMMUNOL & MICROBIOL,MONTREAL,PQ H3J 3J7,CANADA. NIAID,BETHESDA,MD 20892. MCGILL UNIV,DEPT EXPTL MED,MONTREAL,PQ H3G 1A4,CANADA. NR 68 TC 12 Z9 12 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 JUL PY 1995 VL 69 IS 7 BP 4069 EP 4078 PG 10 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600015 PM 7769664 ER PT J AU SENKEVICH, TG WOLFFE, EJ BULLER, RML AF SENKEVICH, TG WOLFFE, EJ BULLER, RML TI ECTROMELIA VIRUS RING FINGER PROTEIN IS LOCALIZED IN VIRUS FACTORIES AND IS REQUIRED FOR VIRUS-REPLICATION IN MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; PERITONEAL-MACROPHAGES; POLYMERASE; MOTIF; DETERMINANTS; INFECTION; SEQUENCE; SUBUNIT; GENOME; GENE AB We have previously described a gene of ectromelia virus (EV) that codes for a 28-kDa RING zinc finger-containing protein (p28) that is nonessential for virus gro,vth in cell culture but is critical for EV pathogenicity in mice (T. G. Senkevich, E. V. Koonin, and R. M. L. Buller, Virology 198:118-128, 1994). Here, we show that, unlike all tested cell cultures, the expression of p28 is required for in vitro replication of EV in murine resident peritoneal macrophages. In macrophages infected with the p28(-) mutant, viral DNA replication was not detected, whereas the synthesis of at least two early proteins was observed. Immunofluorescence and biochemical analyses showed that in EV-infected macrophages or BSC-1 cells, p28 is associated with virus factories. By use of a vaccinia virus expression system to examine different truncated versions of p28, it was shown that the disruption of the specific structure of the RING domain had no influence on the intracellular localization of this protein. When viral DNA replication was inhibited with cytosine arabinoside, p28 was found in distinct, focal structures that may be precursors to the factories. We hypothesize that in macrophages, which are highly specialized, nondividing cells, p28 substitutes for an unknown cellular factor(s) that may be required for viral DNA replication or a stage of virus reproduction between the expression of early genes and the onset of DNA synthesis. In the absence of p28, the attenuation of EV pathogenicity can be explained by a failure of the virus to replicate in macrophage lineage cells at all successive steps in the spread of virus from the skin to its target organ, the liver. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 29 TC 41 Z9 42 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 JUL PY 1995 VL 69 IS 7 BP 4103 EP 4111 PG 9 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600019 PM 7769668 ER PT J AU BOVOLENTA, C LOU, J KANNO, Y PARK, BK THORNTON, AM COLIGAN, JE SCHUBERT, M OZATO, K AF BOVOLENTA, C LOU, J KANNO, Y PARK, BK THORNTON, AM COLIGAN, JE SCHUBERT, M OZATO, K TI VESICULAR STOMATITIS-VIRUS INFECTION INDUCES A NUCLEAR DNA-BINDING FACTOR SPECIFIC FOR THE INTERFERON-STIMULATED RESPONSE ELEMENT SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; NF-KAPPA-B; IFN-BETA GENES; MOUSE L-CELLS; LEADER RNA; TRANSCRIPTION FACTOR; MESSENGER-RNA; DEPENDENT TRANSCRIPTION; REGULATORY FACTOR; MATRIX PROTEIN AB Vesicular stomatitis virus (VSV) has a broad host range. It replicates in the cytoplasm and causes rapid cytopathic effects. We show that following VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many cell types. This factor, tentatively called VSV-induced binding protein (VIBP), was estimated to have an approximate molecular mass of 50 kDa and was distinct from known members of the interferon regulatory factor family, that are known to bind to the ISRE. Induction of VIBP required tyrosine kinase activity but did not require cellular transcription. Treatment of cells with cycloheximide, which inhibits translation, only partially inhibited induction of VIBP. However, type I interferons and staurosporine, both of which inhibit VSV transcription, inhibited VIBP induction. Moreover, a double-stranded RNA analog, poly(I)-poly(C) also induced a DNA-binding activity very similar to that of VIBP. These results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral transcripts. The functional activity of VIBP was analyzed in cells stably transfected with a herpesvirus thymidine kinase-luciferase reporter gene that is under control of the ISRE. While activity of the control promoter without ISRE was strongly inhibited following VSV infection (as a result of virus-mediated transcriptional shutdown of the host cell), the inhibition was reversed by the ISRE-containing promoter, albeit partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other cells tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NINCDS,MOLEC MED & NEUROSCI LAB,BETHESDA,MD 20892. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 65 TC 25 Z9 25 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 JUL PY 1995 VL 69 IS 7 BP 4173 EP 4181 PG 9 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600028 PM 7539506 ER PT J AU LEE, JS GIESE, NA ELKINS, KL YETTER, RA HOLMES, KL HARTLEY, JW MORSE, HC AF LEE, JS GIESE, NA ELKINS, KL YETTER, RA HOLMES, KL HARTLEY, JW MORSE, HC TI EFFECTS OF EXOGENOUS, NONLEUKEMOGENIC, ECOTROPIC MURINE LEUKEMIA-VIRUS INFECTIONS ON THE IMMUNE-SYSTEMS OF ADULT C57BL/6 MICE SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; LEISHMANIA-MAJOR; MAIDS; INDUCTION; DISEASE; ACTIVATION; MOUSE; RESISTANCE; EXPRESSION AB Mouse AIDS (MAIDS) develops in mice infected with a mixture of replication-competent ecotropic and mink lung cell focus-inducing murine leukemia viruses and an etiologic replication-defective virus. Helper viruses are not required for induction of MAIDS, but the time course of disease is accelerated in their presence, To understand the possible contributions of ecotropic murine leukemia viruses to MAIDS pathogenesis, we biologically cloned a series of viruses from the MAIDS-inducing LP-BM5 virus mixture, These viruses were examined for replication in tissues of infected mice and for effects on the immune system, All virus stocks replicated efficiently in mice, Infected animals showed slight lymphadenopathy and splenomegaly due primarily to B-cell proliferation associated with differentiation to immunoglobulin secretion resulting in twofold increases in serum immunoglobulin M levels; however, B-cell responses to helper T-cell-independent antigens were increased rather than decreased as in MAIDS, Analyses of CD8(+) T-cell function showed that cytotoxic T-lymphocyte responses to alloantigens were comparable in control and infected mice, Finally, we showed that infection resulted in enhanced expression of transcripts for interleukin-10, interleukin-4, and gamma interferon, These cytokines can ail contribute to B-cell activation and may promote the expansion of a target cell population for the MAIDS defective virus. C1 NIAID, IMMUNOPATHOL LAB, BETHESDA, MD 20892 USA. CBER, DBP, ENTER & SEXUALLY TRANSMITTED DIS LAB, BETHESDA, MD 20892 USA. US FDA, DIV VACCINES & RELATED PROD APPLICAT, ROCKVILLE, MD 20852 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 40 TC 4 Z9 4 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 JUL PY 1995 VL 69 IS 7 BP 4182 EP 4188 PG 7 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600029 PM 7769677 ER PT J AU BURKLY, L MULREY, N BLUMENTHAL, R DIMITROV, DS AF BURKLY, L MULREY, N BLUMENTHAL, R DIMITROV, DS TI SYNERGISTIC INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN-MEDIATED CELL-FUSION AND INFECTION BY AN ANTIBODY TO CD4 DOMAIN-2 IN COMBINATION WITH ANTI-GP120 ANTIBODIES SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; BINDING-SITE; AIDS RETROVIRUS; RHESUS-MONKEYS; SOLUBLE CD4; T4 MOLECULE; V3 LOOP; HIV-1; GP120; NEUTRALIZATION AB Antibodies to several epitopes of the human immunodeficiency virus type 1 (HIV 1) envelope glycoprotein (gp120-gp41) can synergize in inhibiting HIV-1 infection, In the present study we tested the ability of a monoclonal antibody (MAb), 5A8, which interacts with CD4 domain 2, and other CD4-specific MAbs to synergize with antibodies against gp120. We have previously found that 5A8 inhibits HIV-1 entry without interfering with gp120 binding to CD4, presumably by affecting a postbinding membrane fusion event. Because antibodies to the gp120 V3 loop also affect post-CD4-gp120-binding events, 5A8 was first tested in combination with anti-V3 loop antibodies for possible synergy. The anti-V3 loop antibodies 0.5 beta, NEA-9205, and 110.5 acted synergistically with 5A8 in inhibiting syncytium formation between gp120-gp41- and CD4-expressing cells. A human MAb to an epitope of gp120 involved in CD4 binding, IAM 120-1B1, and another anti-CD4 binding site antibody, PC39,13, also exerted synergistic effects in combination with 5A8. Similarly, an antibody against the gp120 binding site on CD4, 6H10, acted synergistically with an anti-V3 loop antibody, NEA-9205. However, a control anti-CD4 antibody, OKT4, which does not significantly inhibit syncytium formation alone, produced only an additive effect when combined with NEA-9205. Serum from HIV-1-infected individuals, which presumably contains antibodies to the V3 loop and the CD4 binding site, exhibited a strong synergistic effect,vith 5A8 in inhibiting infection by a patient HIV-1 isolate (0104B) and in blocking syncytium formation, These results indicate that therapeutics based on antibodies affecting both non-gp120 binding and gp120 binding epitopes of the target receptor molecule, CD4, could be efficient in patients who already contain anti-gp120 antibodies and could also be used to enhance passive immunization against HIV-1 in combination with anti-gp120 antibodies. C1 NCI,BETHESDA,MD 20892. BIOGEN INC,CAMBRIDGE,MA 02142. NR 30 TC 30 Z9 30 U1 0 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 JUL PY 1995 VL 69 IS 7 BP 4267 EP 4273 PG 7 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600039 PM 7769687 ER PT J AU RAHMAN, A MALHOTRA, P DHAR, R KEWALRAMANI, T THIMMAPAYA, B AF RAHMAN, A MALHOTRA, P DHAR, R KEWALRAMANI, T THIMMAPAYA, B TI EFFECT OF SINGLE-BASE SUBSTITUTIONS IN THE CENTRAL DOMAIN OF VIRUS-ASSOCIATED RNA-I ON ITS FUNCTION SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOVIRUS VAI RNA; ACTIVATED PROTEIN-KINASE; TRANSLATION; INTERFERON; INITIATION; INFECTION; BINDING; PHOSPHORYLATION; TRANSCRIPTION; MUTANTS AB Adenoviruses use virus associated RNA I (VAI RNA) to counteract the cellular antiviral response mediated by the interferon-induced, double-stranded-RNA-activated protein kinase PKR. VAI RNA is a highly structured small RNA which consists of two long duplex regions connected at the center by a complex, short stem-loop. This short stem-loop and the adjacent base-paired regions, referred to as the central domain, bind to PKR and inactivate it. Currently it is not known whether binding of VAI RNA to PKR is dependent solely on the secondary (and tertiary) structure of the central domain or whether nucleotide sequences in the central domain are also critical for this interaction. To address this question, 54 VAI mutants with single-base substitution mutations in the central domain of the RNA were constructed, and their capacities to inhibit the autophosphoryation of PKR in vitro were determined. It was found that although about half of the mutants inhibited PKR activity as efficiently as the wild type, a significant number of mutants lost the inhibitory activity substantially, without a perceptible change in their secondary structures. These results indicate that, in addition to secondary structure, at least some nucleotides in the central domain may be critical for the efficient function of VAI RNA. C1 NORTHWESTERN UNIV,SCH MED,LURIE CANC CTR,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,CHICAGO,IL 60611. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI18029, AI20156] NR 33 TC 18 Z9 18 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 JUL PY 1995 VL 69 IS 7 BP 4299 EP 4307 PG 9 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600043 PM 7769691 ER PT J AU SHIBATA, R HOGGAN, MD BROSCIUS, C ENGLUND, G THEODORE, TS BUCKLERWHITE, A ARTHUR, LO ISRAEL, Z SCHULTZ, A LANE, HC MARTIN, MA AF SHIBATA, R HOGGAN, MD BROSCIUS, C ENGLUND, G THEODORE, TS BUCKLERWHITE, A ARTHUR, LO ISRAEL, Z SCHULTZ, A LANE, HC MARTIN, MA TI ISOLATION AND CHARACTERIZATION OF A SYNCYTIUM-INDUCING, MACROPHAGE/T-CELL LINE-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATE THAT READILY INFECTS CHIMPANZEE CELLS IN-VITRO AND IN-VIVO SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHADENOPATHY-ASSOCIATED VIRUS; T-LYMPHOTROPIC RETROVIRUSES; NF-KAPPA-B; PERSISTENT INFECTION; HIV-INFECTION; NUCLEOTIDE-SEQUENCE; MOLECULAR CLONE; RHESUS-MONKEYS; AIDS VIRUS; HTLV-III AB Fresh human immunodeficiency virus type 1 (HIV-1) isolates from patients with AIDS were screened for infectivity in chimpanzee peripheral blood mononuclear cells (PBMC) to identify strains potentially able to generate high virus loads in an inoculated animal. Only 3 of 23 isolates obtained were infectious in chimpanzee cells. Of these three, only one (HIV-1(DH12)) was able to initiate a productive infection in PBMC samples from all 25 chimpanzees tested. HIV-1(DH12) tissue culture infections were characterized by extremely rapid replication kinetics, profound cytopathicity, and tropism for chimp and human PBMC, primary human macrophage, and several human T-cell lines. An infection was established within 1 week of inoculating a chimpanzee with 50 50% tissue culture infective doses of HIV-1(DH12); cell-free virus was recovered from the plasma at weeks 1, 2, and 4 and was associated with the development of lymphadenopathy. Virus loads during the primary infection and at 6 months postinoculation were comparable to those reported in HIV-1-seropositive individuals. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. NYU,MED CTR,DEPT PATHOL,NEW YORK,NY. NR 69 TC 93 Z9 95 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 JUL PY 1995 VL 69 IS 7 BP 4453 EP 4462 PG 10 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600061 PM 7769705 ER PT J AU UDELSMAN, R LI, DG STAGG, CA HOLBROOK, NJ AF UDELSMAN, R LI, DG STAGG, CA HOLBROOK, NJ TI AORTIC CROSSTRANSPLANTATION BETWEEN YOUNG AND OLD RATS - EFFECT UPON THE HEAT-SHOCK PROTEIN-70 STRESS-RESPONSE SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID EXPRESSION; FIBROBLASTS; GENE; AGE; THERMOSENSITIVITY; HSP70 AB In previous studies we demonstrated that restraint, or immobilization stress, resulted in the induction of HSP70 mRNA in the vasculature of rats. This response was confined to the vascular smooth muscle, was associated with alpha(1)-adrenergic receptor stimulation, and was attenuated with age. In the present study, we examined the; influence of transplanting aged vessels into young animals and young vessels into aged animals to determine if this age-related diminution was due to changes intrinsic to the aorta or the result of alterations in the environment in which the aorta resides. We demonstrate that restraint-induced HSP70 expression in transplanted vessels is influenced to a greater degree by the age of the recipient than by the age of the transplanted vessel. Transplantation of aged vessels into young animals leads to preservation of the response, whereas transplantation of young vessels into aged animals leads to attenuation. These findings indicate that the environment in which the vessel resides is a major factor in determining this molecular response to stress. C1 JOHNS HOPKINS UNIV,SCH MED,ENDOCRINE SURG LAB,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NIDDK NIH HHS [DK02064-04] NR 26 TC 12 Z9 13 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1995 VL 50 IS 4 BP B187 EP B192 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY604 UT WOS:A1995RY60400001 PM 7614229 ER PT J AU SAVILLE, MW LIETZAU, J PLUDA, JM FEUERSTEIN, I ODOM, J WILSON, WH HUMPHREY, RW FEIGAL, E STEINBERG, SM BRODER, S YARCHOAN, R AF SAVILLE, MW LIETZAU, J PLUDA, JM FEUERSTEIN, I ODOM, J WILSON, WH HUMPHREY, RW FEIGAL, E STEINBERG, SM BRODER, S YARCHOAN, R TI TREATMENT OF HIV-ASSOCIATED KAPOSIS-SARCOMA WITH PACLITAXEL SO LANCET LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME AB We investigated whether paclitaxel was active in AIDS-associated Kaposi's sarcoma. We gave 135 mg/m(2) intravenously over 3 hours every 21 days. Follow-up is available on the first 20 patients, mast of whom had advanced Kaposi's sarcoma and severe immunocompromise. Neutropenia was the most frequent dose-limiting toxic effect; novel toxic effects included late fevers, rash, and eosinophilia. Creatinine increased in 2 patients and 1 patient had cardiomyopathy. There were 13 partial responses (65%, 95% CI 41-85%). All 5 patients with pulmonary involvement responded. Paclitaxel appeals to be active against Kaposi's sarcoma as a single agent. Further studies, including a randomised trial, are warranted. C1 NCI,BETHESDA,MD 20892. NIH,WARREN MAGNUSON CLIN CTR,BETHESDA,MD. HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD. NR 9 TC 133 Z9 134 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JUL 1 PY 1995 VL 346 IS 8966 BP 26 EP 28 DI 10.1016/S0140-6736(95)92654-2 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RF985 UT WOS:A1995RF98500012 PM 7603142 ER PT J AU BLOCH, M STAGER, SV BRAUN, AR RUBINOW, DR AF BLOCH, M STAGER, SV BRAUN, AR RUBINOW, DR TI SEVERE PSYCHIATRIC-SYMPTOMS ASSOCIATED WITH PAROXETINE WITHDRAWAL SO LANCET LA English DT Letter C1 NIDOCD,VOICE SPEECH & LANGUAGE BRANCH,VOICE & SPEECH SECT,BETHESDA,MD. NIDOCD,VOICE SPEECH & LANGUAGE BRANCH,LANGUAGE SECT,NEUROIMAGING SCI UNIT,BETHESDA,MD. RP BLOCH, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892, USA. NR 3 TC 37 Z9 37 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JUL 1 PY 1995 VL 346 IS 8966 BP 57 EP 57 DI 10.1016/S0140-6736(95)92691-7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RF985 UT WOS:A1995RF98500052 PM 7603169 ER PT J AU MAGRATH, I AF MAGRATH, I TI BONE-MARROW TRANSPLANTATION SO LANCET LA English DT Letter RP MAGRATH, I (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JUL 1 PY 1995 VL 346 IS 8966 BP 59 EP 60 DI 10.1016/S0140-6736(95)92695-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RF985 UT WOS:A1995RF98500057 PM 7603173 ER PT J AU JEZZARD, P BALABAN, RS AF JEZZARD, P BALABAN, RS TI CORRECTION FOR GEOMETRIC DISTORTION IN ECHO-PLANAR IMAGES FROM B-0 FIELD VARIATIONS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ECHO PLANAR IMAGING, EPI; GEOMETRIC DISTORTION; FIELD MAP CORRECTION ID IMAGING METHODS; NMR; EPI AB A method is described for the correction of geometric distortions occurring in echo planar images. The geometric distortions are caused in large part by static magnetic field inhomogeneities, leading to pixel shifts, particularly in the phase encode direction. By characterizing the field inhomogeneities from a field map, the image can be unwarped so that accurate alignment to conventionally collected images can be made. The algorithm to perform the unwarping is described, and results from echo planar images collected at 1.5 and 4 Tesla are shown. RP JEZZARD, P (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 10 ROOM B1D161,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Jezzard, Peter/0000-0001-7912-2251 NR 17 TC 692 Z9 694 U1 4 U2 27 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 JUL PY 1995 VL 34 IS 1 BP 65 EP 73 DI 10.1002/mrm.1910340111 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RF768 UT WOS:A1995RF76800010 PM 7674900 ER PT J AU LEVAN, G HEDRICH, HJ REMMERS, EF SERIKAWA, T YOSHIDA, MC AF LEVAN, G HEDRICH, HJ REMMERS, EF SERIKAWA, T YOSHIDA, MC TI STANDARDIZED RAT GENETIC NOMENCLATURE SO MAMMALIAN GENOME LA English DT Article ID NORVEGICUS C1 HANNOVER MED SCH,INST VERSUCHSTIERSKUNDE & ZENT TIERLAB,HANNOVER,GERMANY. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. KYOTO UNIV,FAC MED,INST LAB ANIM,KYOTO,JAPAN. HOKKAIDO UNIV,FAC SCI,CHROMOSOME RES UNIT,SAPPORO,HOKKAIDO,JAPAN. RP LEVAN, G (reprint author), GOTHENBURG UNIV,DEPT GENET,MEDICINAREGATAN 9C,S-41390 GOTHENBURG,SWEDEN. NR 15 TC 29 Z9 31 U1 1 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 JUL PY 1995 VL 6 IS 7 BP 447 EP 448 DI 10.1007/BF00360651 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RG988 UT WOS:A1995RG98800001 PM 7579884 ER PT J AU GOLDMUNTZ, EA REMMERS, EF DU, Y ZHA, H MATHERN, P CROFFORD, LJ WILDER, RL AF GOLDMUNTZ, EA REMMERS, EF DU, Y ZHA, H MATHERN, P CROFFORD, LJ WILDER, RL TI GENETIC-MAP OF 16 POLYMORPHIC MARKERS FORMING 3 LINKAGE GROUPS ASSIGNED TO RAT CHROMOSOME-4 SO MAMMALIAN GENOME LA English DT Article AB Sixteen polymorphic markers, including markers for eight new loci, forming three linkage groups, were assigned to rat Chromosome (Chr) 4 by linkage analysis of the progeny of an F-2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. One gene, Igk, was mapped by restriction fragment length poly morphism (RFLP) analysis. One marker for Tcrb was identified by the polymorphic insertion of a repetitive LINE element. The remaining 14 markers contained polymorphic simple sequence repeats (SSRs). Ten were identified in genes (Tgfa, Npy, Prss1, Prss2, Aldr1, Iapp, Prp, Eno2, Cacnl1a1, and Il6), one was identified in a sequence related to a gene (Egr4l1), and three were identified in anonymous DNA segments. The SSR markers were highly polymorphic in 16 inbred rat strains. These markers expand the genetic map of the rat and should be useful in future genetic studies of inbred rats. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 16 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1995 VL 6 IS 7 BP 459 EP 463 DI 10.1007/BF00360654 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RG988 UT WOS:A1995RG98800004 PM 7579887 ER PT J AU FILIE, JD BURBELO, PD KOZAK, CA AF FILIE, JD BURBELO, PD KOZAK, CA TI GENETIC-MAPPING OF THE ALPHA-1 AND ALPHA-2(IV) COLLAGEN GENES TO MOUSE CHROMOSOME-8 SO MAMMALIAN GENOME LA English DT Note ID ENHANCER C1 NIAID,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 7 TC 4 Z9 4 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 JUL PY 1995 VL 6 IS 7 BP 487 EP 487 DI 10.1007/BF00360662 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RG988 UT WOS:A1995RG98800012 PM 7579895 ER PT J AU LYU, MS KOZAK, CA BURBELO, PD AF LYU, MS KOZAK, CA BURBELO, PD TI GENETIC-MAPPING OF GENE ENCODING THE LARGE SUBUNIT OF REPLICATION FACTOR-C (A1-P145) TO MOUSE CHROMOSOME-5 SO MAMMALIAN GENOME LA English DT Note ID RECEPTOR; HOMOLOGY C1 NIAID,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Burbelo, Peter/B-1027-2009 NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1995 VL 6 IS 7 BP 487 EP 488 DI 10.1007/BF00360663 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RG988 UT WOS:A1995RG98800013 PM 7579896 ER PT J AU BADNER, JA YOON, SW TURNER, G BONNER, TI DETERAWADLEIGH, SD AF BADNER, JA YOON, SW TURNER, G BONNER, TI DETERAWADLEIGH, SD TI MULTIPOINT GENETIC-LINKAGE ANALYSIS OF THE M2 HUMAN MUSCARINIC RECEPTOR GENE SO MAMMALIAN GENOME LA English DT Note C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP BADNER, JA (reprint author), NIMH,CLIN NEUROGENET BRANCH,10-3N218,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 1 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 JUL PY 1995 VL 6 IS 7 BP 489 EP 490 DI 10.1007/BF00360666 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RG988 UT WOS:A1995RG98800016 PM 7579899 ER PT J AU BRADHAM, DM PASSANITI, A HORTON, WE AF BRADHAM, DM PASSANITI, A HORTON, WE TI MESENCHYMAL CELL CHONDROGENESIS IS STIMULATED BY BASEMENT-MEMBRANE MATRIX AND INHIBITED BY AGE-ASSOCIATED FACTORS SO MATRIX BIOLOGY LA English DT Article DE BASEMENT MEMBRANE; CHONDROGENESIS; ENGLEBRETH-HOLM-SWARM TUMOR; MATRIGEL ID GROWTH FACTOR-BETA; LIMB CARTILAGE DIFFERENTIATION; CHICK WING BUD; GENE-EXPRESSION; PROTEOGLYCAN SYNTHESIS; COLLAGEN-SYNTHESIS; CHONDROCYTES; FIBRONECTIN; MYOGENESIS; COMPONENTS AB During development of the embryonic limb, differentiation of mesenchymal progenitor cells into chondrocytes is regulated by cell shape, extracellular matrix, and growth and differentiation factors. In this study, reconstituted basement membrane (Matrigel) prepared from mouse Englebreth-Holm-Swarm tumor tissue was found to stimulate mesenchymal cell chondrogenesis in vitro and the production of cartilage at ectopic sites in athymic mice. The rate of chondrogenesis of mesenchymal cells from chick limb bud was increased four-fold by the addition of 400 mu g/ml Matrigel to the media of micromass cultures, and this activity was not blocked by neutralizing antibodies to transforming growth factor-beta (TGF-beta) or fibroblast growth factor (FGF). Mesenchymal cells cultured on Matrigel, but not laminin or collagen type I or IV, formed spheres of condensed cells which stained with Alcian blue. Chick limb-bud mesenchymal cells suspended in Matrigel prepared from tumors grown in C57 mice aged 3, 12, or 26 months formed disks of hyaline cartilage within 2 weeks with wet weights of 59.1 mg, 35.7 mg, and 21.4mg, indicating that the Matrigel from the old animals was less biologically active. In agreement with the in vivo data, Alcian blue staining of proteoglycan was over two-fold higher in micromass cultures supplemented with the Matrigel from young animals than in cultures treated with the Matrigel from old mice. A high-salt wash preparation of Matrigel from tumors grown in old mice increased the rate of chondrogenesis and cartilage production, suggesting that an inhibitor of chondrogenesis is produced by the old host. Thus, Matrigel contains chondrogenic activity distinct from TGF-beta or FGF. The aged host may produce factors that are inhibitory to mesenchymal cell differentiation and adversely affect cartilage formation and repair. RP BRADHAM, DM (reprint author), NIA,GERONTOL RES CTR,BIOL CHEM LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 38 TC 15 Z9 18 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49 POSTFACH 72 01 43, D-70577 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JUL PY 1995 VL 14 IS 7 BP 561 EP 571 DI 10.1016/S0945-053X(05)80005-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RK923 UT WOS:A1995RK92300005 PM 8535606 ER PT J AU SAFAVI, KH MULLER, SA SUMAN, VJ MOSHELL, AN MELTON, LJ AF SAFAVI, KH MULLER, SA SUMAN, VJ MOSHELL, AN MELTON, LJ TI INCIDENCE OF ALOPECIA-AREATA IN OLMSTED COUNTY, MINNESOTA, 1975 THROUGH 1989 SO MAYO CLINIC PROCEEDINGS LA English DT Article ID PATIENT AB Objective: To assess the incidence and natural history of alopecia areata (AA) among unselected patients from a community. Design: We conducted a retrospective population-based descriptive study of AA among residents of Olmsted County, Minnesota, for the period from 1975 through 1989. Material and Methods: After identifying 292 Olmsted County residents first diagnosed with AA during the 15-year study period, me reviewed their complete (inpatient and outpatient) medical records in the community and statistically analyzed the effects of gender and age-group. Results: The overall incidence of AA was 20.2 per 100,000 person-years and did not change with time. Rates were similar in the two genders and over all ages, and lifetime risk was estimated at 1.7%. Eighty-seven percent of patients mere examined by a dermatologist who diagnosed AA, and 29% of cases were confirmed by biopsy, Most patients had mild or moderate disease, but alopecia totalis or universalis developed at some point during the clinical course in 21 patients. Conclusion: This study of the incidence anti natural history of AA in a community shows that this disorder is fairly common and can be seen at all ages, Although spontaneous resolution is expected in most patients, a small but significant proportion of cases (probably approximately 7%) may evolve into severe and chronic hair loss, which may be psychosocially devastating for affected persons. C1 MAYO CLIN & MAYO FDN,CLIN EPIDEMIOL SECT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT DERMATOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,BIOSTAT SECT,ROCHESTER,MN 55905. NIAMSD,EXTRAMURAL PROGRAM,SKIN DIS BRANCH,BETHESDA,MD. FU NIAMS NIH HHS [AR 30582] NR 24 TC 232 Z9 238 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 1995 VL 70 IS 7 BP 628 EP 633 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RG631 UT WOS:A1995RG63100003 PM 7791384 ER PT J AU MEEHAN, S DENUCCI, DJ GUCKES, AD AF MEEHAN, S DENUCCI, DJ GUCKES, AD TI OROFACIAL PAIN RESULTING FROM ILL-FITTING DENTURES SO MILITARY MEDICINE LA English DT Note AB The patient who presents to the physician with a history of facial pain can be a diagnostic challenge. The etiology can be elusive, and this problem is compounded by the subjective nature and the often multi-factorial causes of facial pain. The differential diagnoses to be considered include both local and systemic disorders such as neuropathy, myofascial pain, dentoalveolar pathoses, and psychological disturbances, among others. This paper presents the case of a patient with a history of left auricular pain that was managed for over 12 years with drug therapy with only limited success. A thorough head and neck evaluation revealed probable myofascial pain with a poorly occluding set of complete dentures as a potential etiology, Fabrication of a new set of dentures and modification of the patient's denture-wearing habits has produced an almost complete remission of the pain. This case demonstrates the importance of a dental consultation to rule out a possible oral-musculoskeletal and/or dental etiology in the management of the patient with facial pain. RP MEEHAN, S (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 1995 VL 160 IS 7 BP 366 EP 367 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RM138 UT WOS:A1995RM13800014 PM 7659247 ER PT J AU WERNER, H SHENORR, Z RAUSCHER, FJ MORRIS, JF ROBERTS, CT LEROITH, D AF WERNER, H SHENORR, Z RAUSCHER, FJ MORRIS, JF ROBERTS, CT LEROITH, D TI INHIBITION OF CELLULAR PROLIFERATION BY THE WILMS-TUMOR SUPPRESSOR WT1 IS ASSOCIATED WITH SUPPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR GENE-EXPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA; KIDNEY DEVELOPMENT; IGF-1 RECEPTOR; PRODUCT; PROMOTER; CELLS; TRANSCRIPTS; REPRESSION; MUTATIONS; BINDING AB We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells, The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA), To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. RP WERNER, H (reprint author), NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NCI NIH HHS [CA 47983, CA 52009] NR 47 TC 101 Z9 103 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 JUL PY 1995 VL 15 IS 7 BP 3516 EP 3522 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RE030 UT WOS:A1995RE03000007 PM 7791758 ER PT J AU ORREN, DK PETERSEN, LN BOHR, VA AF ORREN, DK PETERSEN, LN BOHR, VA TI A UV-RESPONSIVE G(2) CHECKPOINT IN RODENT CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HAMSTER OVARY CELLS; ULTRAVIOLET-LIGHT; DNA-REPAIR; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; PYRIMIDINE DIMERS; ATAXIA-TELANGIECTASIA; XERODERMA PIGMENTOSUM; THYMOCYTE APOPTOSIS; REPLICON INITIATION AB We have studied the effect of UV irradiation on the cell cycle progression of synchronized Chinese hamster ovary cells. Synchronization of cells in S or G(2) phase was accomplished by the development of a novel protocol using mimosine, which blocks: cell cycle progression at the G(1)/S boundary. After removal of mimosine, cells proceed synchronously through the S and G(2) phases, allowing manipulation of cells at specific points in either phase. Synchronization of cells in G(1) was achieved by release of cells after a period of serum starvation. Cells synchronized by these methods were UV irradiated at defined points in G(1), S, and G(2), and their subsequent progression through the cell cycle was monitored. UV irradiation of G(1)-synchronized cells caused a dose-dependent delay in entry into S phase. Irradiation of S-phase-synchronized cells inhibited progression through S phase and then resulted in accumulation of cells for a prolonged interval in G(2). Apoptosis of a subpopulation of cells during this extended period was noted, UV irradiation of G(2)-synchronized cells caused a shorter G(2) arrest. The arrest itself and its duration were dependent upon the timing (within G(2) phase) of the irradiation and the UV dose, respectively We have thus defined a previously undescribed (in mammalian cells) UV-responsive checkpoint in G(2) phase. The implications of these findings with respect to DNA metabolism are discussed. C1 NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. UNIV COPENHAGEN HOSP,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. NR 58 TC 82 Z9 82 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 JUL PY 1995 VL 15 IS 7 BP 3722 EP 3730 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RE030 UT WOS:A1995RE03000029 PM 7791779 ER PT J AU PETERSEN, LN ORREN, DK BOHR, VA AF PETERSEN, LN ORREN, DK BOHR, VA TI GENE-SPECIFIC AND STRAND-SPECIFIC DNA-REPAIR IN THE G(1) AND G(2) PHASES OF THE CELL-CYCLE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; DIPLOID HUMAN FIBROBLASTS; UV-INDUCED MUTATIONS; HAMSTER OVARY CELLS; EXCISION REPAIR; SACCHAROMYCES-CEREVISIAE; HPRT GENE; TRANSCRIBED STRAND; PYRIMIDINE DIMERS; ULTRAVIOLET-LIGHT AB We have analyzed the fine structure of DNA repair in Chinese hamster ovary (CHO) cells within the G(1) and G(2) phases of the cell cycle. Repair of inactive regions of the genome has been suggested to increase in the G(2) phase of the cell cycle compared with other phases. However, detailed studies of DNA repair in the G(2) phase of the cell cycle have been hampered by technical limitations. We have used a novel synchronization protocol (D. K. Orren, L. N. Petersen, and V. A. Bohr, Mel. Cell. Biol. 15:3722-3730, 1995) which permitted detailed studies of the fine structure of DNA repair in G(2). CHO cells were synchronized and UV irradiated in G(1) or early G(2). The rate and extent of removal of cyclobutane pyrimidine dimers from an inactive region of the genome and from both strands of the actively transcribed dihydrofolate reductase (DHFR) gene were examined within each phase, The repair of the transcribed strand of the DHFR gene was efficient in both G(1) and G(2), with no major differences between the two cell cycle phases. Neither the nontranscribed strand of the DHFR gene nor an inactive region of the genome was repaired in G(1) or G(2). CHO cells irradiated early in G(2) were more resistant to UV irradiation than cells irradiated in late G(1). Since we found no major difference in repair rates in G(1) and G(2), we suggest that G(2) resistance can be attributed to the increased time (G(2) and G(1)) available for repair before cells commit to DNA synthesis. C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. UNIV COPENHAGEN HOSP,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. NR 47 TC 32 Z9 32 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 JUL PY 1995 VL 15 IS 7 BP 3731 EP 3737 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RE030 UT WOS:A1995RE03000030 PM 7791780 ER PT J AU MATOSKOVA, B WONG, WT SALCINI, AE PELICCI, PG DIFIORE, PP AF MATOSKOVA, B WONG, WT SALCINI, AE PELICCI, PG DIFIORE, PP TI CONSTITUTIVE PHOSPHORYLATION OF EPS8 IN TUMOR-CELL LINES - RELEVANCE TO MALIGNANT TRANSFORMATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTOR; SIGNAL TRANSDUCTION; MITOGENIC SIGNAL; PROTEIN; DOMAINS; SH2; IDENTIFICATION; PHOSPHATASES; CLONING AB eps8, a recently identified tyrosine kinase substrate, has been shown to augment epidermal growth factor (EGF) responsiveness, implicating it in EGF receptor (EGFR)-mediated mitogenic signaling. We investigated the status of eps8 phosphorylation in normal and transformed cells and the role of eps8 in transformation. In NIH 3T3 cells overexpressing EGFR (NIH-EGFR), eps8 becomes rapidly phosphorylated upon EGF stimulation. At receptor-saturating doses of EGF, similar to 30% of the eps8 pool is tyrosine phosphorylated. Under physiological conditions of activation (i.e., at low receptor occupancy), corresponding to the 50% effective dose of EGF for mitogenesis, similar to 3 to 4% of the eps8 contains phosphotyrosine. In human tumor cell lines, we detected constitutive tyrosine phosphorylation of eps8, with a stoichiometry (similar to 5%) similar to that associated with potent mitogenic response in NIH-EGFR cells. Overexpression of eps8 was able to transform NIH 3T3 cells under limiting conditions of activation of the EGFR pathway. Concomitant tyrosine phosphorylation of eps8 and she, but not of rasGAP, phospholipase C-gamma, and eps15, was frequently detected in tumor cells. This suggested that eps8 and she might be part of a pathway which is preferentially selected in some tumors. Cooperation between these two transducers was further indicated by the finding of their in vivo association. This association was, at least in part, dependent on recognition of shc by the SH3 domain of eps8. Our results indicate that eps8 is physiologically part of the EGFR-activated signaling and that its alterations can contribute to the malignant phenotype. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. MONTELUCE POLICLIN,IST MED INTERNA & SCI ONCOL,PERUGIA,ITALY. UNIV PARMA,IST PATOL MED,I-43100 PARMA,ITALY. FAC MED & CHIRURG BARI,IST MICROBIOL,BARI,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 44 TC 61 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1995 VL 15 IS 7 BP 3805 EP 3812 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RE030 UT WOS:A1995RE03000038 PM 7791787 ER PT J AU JANCZEWSKI, DN MODI, WS STEPHENS, JC OBRIEN, SJ AF JANCZEWSKI, DN MODI, WS STEPHENS, JC OBRIEN, SJ TI MOLECULAR EVOLUTION OF MITOCHONDRIAL-12S RNA AND CYTOCHROME-B SEQUENCES IN THE PANTHERINE LINEAGE OF FELIDAE SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE PHYLOGENY; FELIDAE; MITOCHONDRIAL DNA; CARNIVORA ID CHROMOSOME-BANDING PATTERNS; DNA EVOLUTION; INTERRELATIONSHIPS; AMPLIFICATION; CARNIVORES; PRIMATES; MAMMALS; CANIDS AB DNA sequence comparisons of two mitochondrial DNA genes were used to infer phylogenetic relationships among 17 Felidae species, notably 15 in the previously described pantherine lineage. The polymerase chain reaction (PCR) was used to generate sequences of 358 base pairs of the mitochondrial 12S RNA gene and 289 base pairs of the cytochrome b protein coding gene. DNA sequences were compared within and between 17 felid and five nonfelid carnivore species. Evolutionary trees were constructed using phenetic, cladistic, and maximum likelihood algorithms. The combined results suggested several phylogenetic relationships including (1) the recognition of a recently evolved monophyletic genus Panthera consisting of Panthera lee, P. pardus, P. onca, P. uncia, P. tigris, and Neofelis nebulosa; (2) the recent common ancestry of Acinonyx jubatus, the African cheetah, and Puma concolor, the American puma; and (3 ) two golden cat species, Profelis temmincki and Profelis aurata, are not sister species, and the latter is strongly associated with Caracal caracal. These data add to the growing database of vertebrate mtDNA sequences and, given the relatively recent divergence among the felids represented here (1-10 Myr), allow 12S and cytochrome b sequence evolution to be addressed over a time scale different from those addressed in most work on vertebrate mtDNA. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. RP JANCZEWSKI, DN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 55 TC 80 Z9 91 U1 3 U2 22 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 1995 VL 12 IS 4 BP 690 EP 707 PG 18 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA RE693 UT WOS:A1995RE69300017 PM 7544865 ER PT J AU MCMILLIAN, MK HUDSON, PM SIMMONS, KL DREYER, DA HONG, JS PENNYPACKER, KR AF MCMILLIAN, MK HUDSON, PM SIMMONS, KL DREYER, DA HONG, JS PENNYPACKER, KR TI ACUTE REPEATED NICOTINE INJECTIONS INCREASE ENKEPHALIN AND DECREASE AP-1 DNA-BINDING ACTIVITY IN RAT ADRENAL-MEDULLA SO MOLECULAR BRAIN RESEARCH LA English DT Note DE ENKEPHALIN; ADRENAL; CHROMAFFIN; NICOTINE; C-FOS RELATED ANTIGEN; AP-1 ID TYROSINE-HYDROXYLASE GENE; C-FOS TRANSCRIPTION; CHROMAFFIN CELLS; MESSENGER-RNA; EXPRESSION; PROENKEPHALIN; STIMULATION; MECHANISMS; ACTIVATION; PEPTIDES AB Previously we reported that a single injection of nicotine decreased AP-1 DNA binding activity in adrenal medullae, although chronic bidaily nicotine (and saline) injections increased this binding activity [15]. Repeated acute nicotine injections (3 mg/kg i.p., 7 injections equi-spaced over a 3 h period) effectively increased adrenal tyrosine hydroxylase [3] and [Met(5)]enkephalin levels and also profoundly decreased adrenal medulla AP-1 DNA binding activity for over 8 h. RP MCMILLIAN, MK (reprint author), NIEHS,ENVIRONM NEUROSCI LAB,MD14-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 23 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1995 VL 31 IS 1-2 BP 210 EP 214 DI 10.1016/0169-328X(95)00053-U PG 5 WC Neurosciences SC Neurosciences & Neurology GA RE026 UT WOS:A1995RE02600022 ER PT J AU ZHOU, J REFUERZO, J BONDY, C AF ZHOU, J REFUERZO, J BONDY, C TI GRANULOSA-CELL DNA-SYNTHESIS IS STRICTLY CORRELATED WITH THE PRESENCE OF INSULIN-LIKE GROWTH-FACTOR-I AND ABSENCE OF C-FOS/C-JUN EXPRESSION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; IGF-I; RAT; DEATH; FOLLICLE; MATURE; ACID AB Insulin-like growth factor I (IGF-I) mRNA is selectively expressed by a subset of rat ovarian follicles. To elucidate the biological role and regulation of follicular IGF-I, we have analyzed individual follicles with respect to IGF-I production, DNA synthesis, and c-fos and c-jun expression, since AP-1 complex components have been implicated both in regulation of IGF-I gene expression and cell proliferation. IGF-I mRNA localization, bromodeoxyuridine (BRDU) incorporation, and c-fos and c-jun immunoreactivity were compared in serial sections from prepubertal and mature rat ovaries. BRDU incorporation is exclusively concentrated in IGF-I-expressing follicles in both prepubertal and mature rats, with further intrafollicular correlation between local concentrations of BRDU-positive granulosa cells and IGF-I mRNA. Furthermore, there is a striking negative correlation between IGF-I mRNA localization and follicular fos/jun immunoreactivity. Both c-fos and c-jun are readily detected in granulosa cells of luteinized follicles where IGF-I mRNA is never found. Immunoreactive c-jun but not c-fos is detected in granulosa cells of atretic follicles, while neither c-fos nor c-jun is detected in IGF-I mRNA-positive granulosa cells, These data implicate IGF-I in granulosa cell proliferation and the fos/jun heterodimer in granulosa cell luteinization, while expression of c-jun in the absence of c-fos may be implicated in programmed granulosa cell death. RP ZHOU, J (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 17 TC 37 Z9 38 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1995 VL 9 IS 7 BP 924 EP 931 DI 10.1210/me.9.7.924 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RG397 UT WOS:A1995RG39700014 PM 7476974 ER PT J AU FITTS, MG METZGER, DW HENDERSHOT, LM MAGE, RG AF FITTS, MG METZGER, DW HENDERSHOT, LM MAGE, RG TI THE RABBIT B-CELL ANTIGEN RECEPTOR IS NONCOVALENTLY ASSOCIATED WITH UNIQUE HETEROMERIC PROTEIN COMPLEXES - POSSIBLE INSIGHTS INTO THE MEMBRANE IGM/IGD COEXPRESSION PARADOX SO MOLECULAR IMMUNOLOGY LA English DT Article DE IMMUNOGLOBULIN; IGM; IGD; RABBIT; B CELL RECEPTOR ID MOLECULAR-COMPONENTS; LYMPHOCYTE-B; IG-BETA; IMMUNOGLOBULIN; IDENTIFICATION; PRODUCT; CHAINS; ALPHA; GENE; MB-1 AB We describe several proteins that are components of the rabbit B cell receptor complex. Two proteins (37 kDa and 42 kDa) were found in non-covalent association with IgM expressed on B cells from peripheral blood. These proteins were also immunoprecipitated by anti-B29 (Ig-beta) and anti-mbl (Ig-alpha) monoclonal antibodies. As in the mouse and human, the IgM associated molecules were found as heteromeric structures with non-reduced apparent molecular weights of approximately 70-75 kDa. On rabbit B cells we also found these proteins in a 100-135 kDa complex which may represent trimeric or tetrameric structures. By Western blot, the 37 kDa protein was identified as rabbit Ig-beta (B29), suggesting that the 42 kDa protein is rabbit Ig-alpha. These data suggest that rabbit IgM is associated with both Ig-alpha/beta and Ig-(alpha beta)(2) or alpha beta gamma complexes. When similar immunoprecipitation studies were performed on lysates made from B cells isolated from appendix follicles, we found two additional IgM associated protein complexes containing 34 kDa and 36 kDa proteins. C1 NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. MED COLL OHIO, DEPT MICROBIOL, TOLEDO, OH 43699 USA. ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA. OI Metzger, Dennis/0000-0002-8000-9907 FU NIGMS NIH HHS [GM-43576] NR 43 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 1995 VL 32 IS 10 BP 753 EP 759 DI 10.1016/0161-5890(95)00028-D PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA RR823 UT WOS:A1995RR82300008 PM 7659100 ER PT J AU MILLER, RH SARVER, N AF MILLER, RH SARVER, N TI HIV ACCESSORY PROTEINS - EMERGING THERAPEUTIC TARGETS SO MOLECULAR MEDICINE LA English DT Review C1 NIAID,DIV AIDS,BASIC SCI PROGRAM,TARGETED INTERVENT BRANCH,BETHESDA,MD 20892. NR 11 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 1995 VL 1 IS 5 BP 479 EP 485 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RL912 UT WOS:A1995RL91200002 PM 8529114 ER PT J AU REDA, T BLUMENTHAL, R MULLER, P HERRMANN, A AF REDA, T BLUMENTHAL, R MULLER, P HERRMANN, A TI INFLUENCE OF THE SPECTRIN NETWORK ON FUSION OF INFLUENZA-VIRUS WITH RED-BLOOD-CELLS SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article DE INFLUENZA VIRUS; FUSION; ERYTHROCYTE MEMBRANE; SPECTRIN; LIPID PHASE ID HUMAN-ERYTHROCYTE-MEMBRANE; TRANSBILAYER PHOSPHOLIPID DISTRIBUTION; VESICULAR STOMATITIS-VIRUS; PH-DEPENDENT FUSION; OSMOTIC FORCES; VESICLE PRODUCTION; FLUORESCENCE; KINETICS; GHOSTS; HEMAGGLUTININ AB We examined the influence of the physical state of the membrane skeleton on low pH fusion of influenza virus A/PR 8/34 with intact human red blood cells. Spectrin, the major component of the skeleton, is known to become denaturated at 50 degrees C. After heat treatment of erythrocytes at 50 degrees C we observed an enhanced kinetics of fusion monitored spectrofluorometrically by the octadecylrhodamine fluorescence dequenching assay, while the extent of fusion was not affected. The accelerated fusion of influenza virus after preincubation of red blood cells at 50 degrees C is not mediated by alterations of the lipid phase of the target. From ESR measurements using spin-labelled phospholipids we conclude that heat-induced alterations of the spectrin network did not affect either the phospholipid asymmetry or the fluidity of the exoplasmic and the cytoplasmic leaflets of the erythrocyte membrane. Moreover, as deduced from our previous investigations, the swelling behaviour of red blood cells could not be responsible for the observed effect. Possible mechanisms for the spectrin effect include a change in the ability of the target membrane to bend locally, and a change in the rate of formation and development of the fusion pore. C1 HUMBOLDT UNIV BERLIN,FAK MATH NAT WISSENSCHAFTLICHE 1,INST BIOL BIOPHYS,D-10115 BERLIN,GERMANY. NCI,BETHESDA,MD 20892. NR 42 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JUL-SEP PY 1995 VL 12 IS 3 BP 271 EP 276 DI 10.3109/09687689509072427 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RP090 UT WOS:A1995RP09000005 PM 8520628 ER PT J AU KENNEY, NJ HUANG, RP JOHNSON, GR WU, JX OKAMURA, D MATHENY, W KORDON, E GULLICK, WJ PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED AF KENNEY, NJ HUANG, RP JOHNSON, GR WU, JX OKAMURA, D MATHENY, W KORDON, E GULLICK, WJ PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED TI DETECTION AND LOCATION OF AMPHIREGULIN AND CRIPTO-1 EXPRESSION IN THE DEVELOPING POSTNATAL MOUSE MAMMARY-GLAND SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE EGF-LIKE LIGANDS; POSTNATAL DEVELOPMENT; RT-PCR; IMMUNOCYTOCHEMISTRY; IMMUNOBLOTTING ID EPIDERMAL GROWTH-FACTOR; CARCINOMA CELL-LINE; FACTOR RECEPTOR; DUCTAL MORPHOGENESIS; MITOGENIC ACTIVITY; EPITHELIAL-CELLS; MESSENGER-RNA; FACTOR-ALPHA; FACTOR-BETA; GENE AB Amphiregulin (Ar) and Cripto-1 (Cr-1) are growth promoting peptides that share amino acid sequence homology with epidermal growth factor (EGF). The present study examined Ar and Cr-1 mRNA and protein expression during various stages of C57BL/6 mouse mammary morphogenesis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect transcripts for Ar and Cr-1 at all stages of mammary development. Immunocytochemical (ICC) localization demonstrated that in virgin 4-week to mature 12-week-old mouse fourth inguinal mammary gland, Ar and Cr-1 are expressed in the stromal cells, luminal epithelial cells, and myoepithelial cells of the branching ducts. Ar, and to lesser extent Cr-1, were also found in the epithelial cap cells and in the luminal epithelial cells of the advancing terminal end bud (TEB) from virgin 4-week and 6-week-old mice. Western blot analysis demonstrated that both Ar (28 and 26 kDa) and Cr-1 (90, 67, 56, and 21 kDa) proteins are expressed in virgin, 13.5 day midpregnant and in the 14 day lactating mammary gland. In addition, Ar and Cr-1 are associated with developing alveolar structures as determined by ICC. These results imply that together with EGF and transforming growth factor alpha (TGF alpha), Ar and Cr-1 may play salient roles as modifiers in the morphogenesis and differentiation of the mammary gland. (C) 1995 Wiley-Liss, Inc. C1 LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. SUGEN INC,PHARMACEUT,REDWOOD CITY,CA. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON WC2A 3PX,ENGLAND. FU NCI NIH HHS [CA54233]; NICHD NIH HHS [HD 28427] NR 35 TC 69 Z9 69 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUL PY 1995 VL 41 IS 3 BP 277 EP 286 DI 10.1002/mrd.1080410302 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA RE839 UT WOS:A1995RE83900001 PM 8588926 ER PT J AU COLE, R HALLETT, M COHEN, LG AF COLE, R HALLETT, M COHEN, LG TI DOUBLE-BLIND TRIAL OF BOTULINUM TOXIN FOR TREATMENT OF FOCAL HAND DYSTONIA SO MOVEMENT DISORDERS LA English DT Article DE BOTULINUM TOXIN; DYSTONIA; WRITERS CRAMP; CLINICAL TRIAL ID WRITERS CRAMP; INJECTIONS AB Ten patients with focal dystonia of the hand, all of whom had benefited in an open-label study of botulinum toxin, were treated with botulinum toxin-A in a double-blind study. Response was assessed by three measures: (a) subjective rating, provided by patients' reports of the effect of the injections on the dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale) to measure muscle strength in all patients, timing of a writing sample and counting the number of errors of writing off-the-line in six patients with writer's cramp, counting the number of errors on a standard test of transcription in two patients with stenographer's cramp, and rating by professional musicians of the performances of two patients with musician's cramp; and (c) physicians' rating, provided by a review of the patients' videotaped performance by neurologists who were unaware of which treatment was administered. Eight of the 10 patients had greater subjective improvement with botulinum toxin than with placebo, and this impression was verified by at least one objective test in six patients. Two patients failed to have a better response to botulinum toxin than to placebo, and their reports were verified by the objective tests. This study confirms the efficacy of botulinum toxin in many patients with focal hand dystonia. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 10 TC 61 Z9 61 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 1995 VL 10 IS 4 BP 466 EP 471 DI 10.1002/mds.870100411 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RG385 UT WOS:A1995RG38500010 PM 7565828 ER PT J AU HECHT, JT NELSON, LD CROWDER, E WANG, Y ELDER, FFB HARRISON, WR FRANCOMANO, CA PRANGE, CK LENNON, GG DEERE, M LAWLER, J AF HECHT, JT NELSON, LD CROWDER, E WANG, Y ELDER, FFB HARRISON, WR FRANCOMANO, CA PRANGE, CK LENNON, GG DEERE, M LAWLER, J TI MUTATIONS IN EXON 17B OF CARTILAGE OLIGOMERIC MATRIX PROTEIN (COMP) CAUSE PSEUDOACHONDROPLASIA SO NATURE GENETICS LA English DT Article ID THROMBOSPONDIN; EXPRESSION; DYSPLASIA; DOMINANT; COLLAGEN; BINDING; GENE AB Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familiar and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia. C1 UNIV TEXAS,SCH MED,DEPT PATHOL,HOUSTON,TX 77225. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94551. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115. RP HECHT, JT (reprint author), UNIV TEXAS,SCH MED,DEPT PEDIAT,POB 20708,HOUSTON,TX 77225, USA. FU NCI NIH HHS [CA16672]; NHLBI NIH HHS [HL49081] NR 37 TC 252 Z9 256 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1995 VL 10 IS 3 BP 325 EP 329 DI 10.1038/ng0795-325 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RG386 UT WOS:A1995RG38600017 PM 7670471 ER PT J AU CHONG, SS MCCALL, AE COTA, J SUBRAMONY, SH ORR, HT HUGHES, MR ZOGHBI, HY AF CHONG, SS MCCALL, AE COTA, J SUBRAMONY, SH ORR, HT HUGHES, MR ZOGHBI, HY TI GAMETIC AND SOMATIC TISSUE-SPECIFIC HETEROGENEITY OF THE EXPANDED SCA1 CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1 SO NATURE GENETICS LA English DT Article ID HUNTINGTONS-DISEASE; INSTABILITY; EXPANSION; GENE; MUTATIONS; LENGTH; ORIGIN; SEX AB Spinocerebellar ataxia type 1 is associated with expansion of an unstable CAG repeat within the SCA1 gene. Male gametic heterogeneity of the expanded repeat is demonstrated using single sperm and low-copy genome analysis. Low-copy genome analysis of peripheral blood also reveals somatic heterogeneity of the expanded SCA1 allele, thus establishing mitotic instability at this locus. Comparative analysis of a large normal allele and a small affected allele suggests a role of midstream CAT interspersions in stabilizing long (CAG)(n) stretches. Within the brain, tissue-specific mosaicism of the expanded allele is also observed. The differences in SCA1 allele heterogeneity between sperm and blood and within the brain parallels the findings in Huntington disease, suggesting that both disorders share a common mechanism for tissue-specific instability. C1 BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216. UNIV MINNESOTA,INST HUMAN GENET,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. RI Chong, Samuel/D-8098-2015 FU NINDS NIH HHS [NS22920, NS27699] NR 40 TC 138 Z9 139 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1995 VL 10 IS 3 BP 344 EP 350 DI 10.1038/ng0795-344 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RG386 UT WOS:A1995RG38600020 PM 7670474 ER PT J AU BELLUS, GA MCINTOSH, I SMITH, EA AYLSWORTH, AS KAITILA, I HORTON, WA GREENHAW, GA HECHT, JT FRANCOMANO, CA AF BELLUS, GA MCINTOSH, I SMITH, EA AYLSWORTH, AS KAITILA, I HORTON, WA GREENHAW, GA HECHT, JT FRANCOMANO, CA TI A RECURRENT MUTATION IN THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH-FACTOR RECEPTOR-3 CAUSES HYPOCHONDROPLASIA SO NATURE GENETICS LA English DT Letter ID DIVERSITY; FAMILY; GENE C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,BRAIN & DEV RES CTR,CHAPEL HILL,NC 27599. HELSINKI UNIV HOSP,DEPT CLIN GENET,SF-00290 HELSINKI,FINLAND. SHRINERS HOSP CRIPPLED CHILDREN,DEPT RES,PORTLAND,OR 97201. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX 77225. FU NIAMS NIH HHS [AR41135]; NICHD NIH HHS [HD24061]; NIDCR NIH HHS [DE10293] NR 28 TC 298 Z9 305 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1995 VL 10 IS 3 BP 357 EP 359 DI 10.1038/ng0795-357 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA RG386 UT WOS:A1995RG38600023 PM 7670477 ER PT J AU GOLDMAN, D AF GOLDMAN, D TI DOPAMINE TRANSPORTER, ALCOHOLISM AND OTHER DISEASES SO NATURE MEDICINE LA English DT Editorial Material ID GENE RP GOLDMAN, D (reprint author), NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 12 TC 4 Z9 4 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 1995 VL 1 IS 7 BP 624 EP 625 DI 10.1038/nm0795-624 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RQ066 UT WOS:A1995RQ06600029 PM 7585136 ER PT J AU MACIEJEWSKI, JP WEICHOLD, FF YOUNG, NS CARA, A ZELLA, D REITZ, MS GALLO, RC AF MACIEJEWSKI, JP WEICHOLD, FF YOUNG, NS CARA, A ZELLA, D REITZ, MS GALLO, RC TI INTRACELLULAR EXPRESSION OF ANTIBODY FRAGMENTS DIRECTED AGAINST HIV REVERSE-TRANSCRIPTASE PREVENTS HIV-INFECTION IN-VITRO SO NATURE MEDICINE LA English DT Article ID EPSTEIN-BARR VIRUS; SINGLE-CHAIN FV; ESCHERICHIA-COLI; MAMMALIAN-CELLS; GENE-THERAPY; REPLICATION; PROTEIN; TYPE-1; VECTOR; DNA AB We have tested a novel strategy of intracellular immunization to block human immunodeficiency virus (HIV) infection. The expression of a specific antibody within a cell was achieved by transduction of genes that encode for immunoglobulin chains with specificity to viral reverse transcriptase. We demonstrated that inhibition of this enzyme makes cells resistant to HIV infection by blocking an early stage of viral replication. If high efficiency transduction with a stable vector into lymphohaematopoietic stem cells or mature lymphocytes can be achieved, gene transfer-mediated intracellular immunization might be a feasible treatment strategy in AIDS. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 41 TC 78 Z9 78 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 1995 VL 1 IS 7 BP 667 EP 673 DI 10.1038/nm0795-667 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RQ066 UT WOS:A1995RQ06600042 PM 7585149 ER PT J AU ERICKSON, JW AF ERICKSON, JW TI THE NOT-SO-GREAT ESCAPE SO NATURE STRUCTURAL BIOLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 PROTEASE; INHIBITORS; TARGET; AIDS AB Structural analysis reveals mechanisms of drug resistance to HIV-1 protease inhibitors. These results have implications for the design of drugs and therapeutic strategies to combat drug resistance in AIDS. RP ERICKSON, JW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702, USA. NR 33 TC 75 Z9 75 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUL PY 1995 VL 2 IS 7 BP 523 EP 529 DI 10.1038/nsb0795-523 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TD550 UT WOS:A1995TD55000004 PM 7664118 ER PT J AU JOSEPH, JA ALGERI, S DECESARE, A COMUZIO, M ERAT, S KELLY, J CAGNOTTO, A MENNINI, T AF JOSEPH, JA ALGERI, S DECESARE, A COMUZIO, M ERAT, S KELLY, J CAGNOTTO, A MENNINI, T TI A REDUCED CALORIE-HIGH FIBER DIET RETARDS AGE-ASSOCIATED DECREASES IN MUSCARINIC RECEPTOR SENSITIVITY SO NEUROBIOLOGY OF AGING LA English DT Article DE CALORIC RESTRICTION; SIGNAL TRANSDUCTION; AGING; DOPAMINE RELEASE; GTPASE ACTIVITY ID HEAVY-PARTICLE IRRADIATION; LIFELONG HYPOCALORIC DIET; MEMBRANE FLUIDITY; STRIATAL DOPAMINE; FOOD RESTRICTION; SIGNAL TRANSDUCTION; LIPID-PEROXIDATION; GTPASE ACTIVITY; G-PROTEINS; RAT-BRAIN AB The effects of a reduced calorie-high fiber diet (RCHF) were examined on three cholinergic signal transduction (ST) parameters: (a) oxotremorine enhancement of K+-evoked dopamine release and (b) carbachol-stimulated low KM GTPase activity [an indicator of muscarinic receptor (mAChR)-G protein coupling/uncoupling], and (c) [H-3]Quinuclidinyl benzilate (QNB) autoradiography. Comparisons were made among: young control (6 months), old normal control, old reduced calorie high fiber [both 24 months)]. The results indicated that old reduced calorie high fiber rats (1900 kcal/kg/day, 2.4%, lipids 2.4%, fiber 28%, carbohydrates 40.7%) as compared to the old normal control rats (3000 kcal/kg/day, 4.8% lipids, 4.2% fiber, carbohydrates 61.5%) showed a retardation of age-related deficits in dopamine release (a above) and GTPase activity (b above). These parameters were 25% higher in the old reduced calorie high fiber rats as compared to old normal controls and did not differ from young controls, even though there was no increase in mAChR concentration in the restricted group. Thus, these results indicate that a reduced calorie high fiber diet as utilized in these experiments was effective in retarding the age-related decrements in two of three signal transduction parameters. They are discussed in terms of the induction of membrane changes (e.g., fluidity) or related decreases in oxidative stress by the restricted diet that may be involved in these signal transduction effects. C1 SIGMA TAU PHARMACEUT CO, INST SENESCENCE, ROME, ITALY. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. MARIO NEGRI INST PHARMACOL RES, MILAN, ITALY. RP JOSEPH, JA (reprint author), TUFTS UNIV, USDA,ARS,HUMAN NUTR RES CTR AGING,ROOM 919, 711 WASHINGTON ST, BOSTON, MA 02111 USA. OI Cagnotto, Alfredo/0000-0002-1390-8240 NR 60 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1995 VL 16 IS 4 BP 607 EP 612 DI 10.1016/0197-4580(95)00073-N PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA RL488 UT WOS:A1995RL48800013 PM 8544911 ER PT J AU KAMETANI, H IIJIMA, S SPANGLER, EL INGRAM, DK JOSEPH, JA AF KAMETANI, H IIJIMA, S SPANGLER, EL INGRAM, DK JOSEPH, JA TI IN-VIVO ASSESSMENT OF STRIATAL DOPAMINE RELEASE IN THE AGED MALE FISCHER-344 RAT SO NEUROBIOLOGY OF AGING LA English DT Article DE CHOLINERGIC SYSTEM; HIGH POTASSIUM; AMPHETAMINE; OXOTREMORINE; MICRODIALYSIS; MOTOR PERFORMANCE ID FREELY MOVING RATS; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; CHOLINE-ACETYLTRANSFERASE; INTRACEREBRAL DIALYSIS; NUCLEUS-ACCUMBENS; RECEPTOR SUBTYPES; CORPUS STRIATUM; MESSENGER-RNA; AMPHETAMINE AB A microdialysis probe was implanted into the striatum of young (4- to 5-month-old) and aged (26- to 27-month-old) Fischer 344 male rats to assess age-related alterations in striatal dopamine (DA) release. Basal levels of DA and the magnitude of DA response evoked by 50 mM and 100 mM high potassium (K+) in aged rats were similar to those in young rats. Furthermore, K+-evoked DA release did not correlate with motor performance within either age group. In contrast, amphetamine (250 mu M) evoked-DA release of aged rats was significantly lower than that of young rats. Moreover, the enhancement of K+-evoked DA release by oxotremorine (500 mu M) was significantly attenuated in aged rats. These results indicate that a putative DA release mechanism and its cholinergic modulation of the aged striatum are impaired. C1 NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. UNIV TOKYO,SCH MED,DEPT GERIATR,BUNKYO KU,TOKYO 113,JAPAN. TUFTS UNIV,HUMAN NUTR RES CTR AGING,USDA,ARS,BOSTON,MA 02111. NR 56 TC 37 Z9 37 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1995 VL 16 IS 4 BP 639 EP 646 DI 10.1016/0197-4580(95)00047-I PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA RL488 UT WOS:A1995RL48800017 PM 8544915 ER PT J AU MASTORAKOS, G PATCHEV, VK CHADER, GJ CHROUSOS, GP GAUDET, SJ AF MASTORAKOS, G PATCHEV, VK CHADER, GJ CHROUSOS, GP GAUDET, SJ TI DIFFERENCES IN ARYLALKYLAMINE N-ACETYLTRANSFERASE ACTIVITY BETWEEN INFLAMMATORY DISEASE-SUSCEPTIBLE LEWIS AND DISEASE-RESISTANT FISCHER RATS SO NEUROENDOCRINOLOGY LA English DT Article DE PINEAL GLAND; MELATONIN; CIRCADIAN RHYTHM; ARYLALKYLAMINE N-ACETYLTRANSFERASE; INFLAMMATION; LEWIS RATS; FISCHER RATS ID CORTICOTROPIN-RELEASING HORMONE; WALL INDUCED POLYARTHRITIS; PINEAL-GLAND; INDUCED ARTHRITIS; MELATONIN; SECRETION; SEROTONIN; INVITRO; IDENTIFICATION; PURIFICATION AB Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred strains characterized, respectively, by susceptibility and resistance to inflammatory disease. The susceptibility of LEW/N rats to inflammation has been associated with deficient corticotropin-releasing hormone (CRH), ACTH, and corticosterone responses to inflammatory stimuli, specifically attributed to a global impairment in hypothalamic CRH neuron function. In contrast to the LEW/N rats, F344/N rats demonstrate an intact hypothalamic-pituitary-adrenal (HPA) axis. Melatonin, a neurohormone initially isolated in the pineal gland,. has been implicated with inhibition of the HPA axis. To investigate melatonin synthesis and secretion in LEW/N and F344/N rats, we examined the diurnal activity of pineal arylalkylamine N-acetyltransferase (NAT1), the rate-limiting enzyme in melatonin biosynthesis, which demonstrates circadian rhythmicity, as well as the diurnal levels of serum melatonin, in both strains. Arylamine N-acetyltransferase (NAT2), a related enzyme activity, thought not to be regulated in a circadian manner, was examined as a control of NAT1 activity. Pineal NAT1 activity peak was observed later and reached significantly higher levels in LEW/N than in F344/N rats. Serum melatonin levels reflected the circadian pattern of the NAT1 activity, without, however, showing any quantitative differences between the two strains. Time-course of pineal NAT1 activity response to beta-adrenergic stimulation was parallel in the two rat strains, whereas the magnitude of the response was greater in LEW/N than in F344/N rats. No circadian or major quantitative differences in NAT2 activity were found between the two strains. Size-exclusion HPLC chromatograms of NAT1 activity revealed similar patterns in both rat strains. These findings demonstrate a difference in the circadian and beta-adrenergic-stimulated regulation of melatonin synthesis in the two rat strains. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 40 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1995 VL 62 IS 1 BP 71 EP 78 DI 10.1159/000126990 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA RJ611 UT WOS:A1995RJ61100009 PM 7566441 ER PT J AU COCCHI, D CATTANEO, C LANE, MA INGRAM, DK CUTLER, RG ROTH, GS AF COCCHI, D CATTANEO, C LANE, MA INGRAM, DK CUTLER, RG ROTH, GS TI EFFECT OF LONG-TERM DIETARY RESTRICTION ON THE SOMATOTROPIC AXIS IN ADULT AND AGED MONKEYS SO NEUROENDOCRINOLOGY LETTERS LA English DT Article ID GROWTH-HORMONE SECRETION; LIFELONG HYPOCALORIC DIET; SOMATOMEDIN; SERUM AB Previous studies showed that moderate dietary restriction has beneficial effects on the normal course of aging. The aim of the present study was to evaluate the ability of long-term diet restriction to modify the age-related reduction of somatotrophic function in monkeys. Plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) progressively decreased with advancing age. Dietary restriction reduced plasma IGF-1 levels only in-adult monkeys although a non-significant trend toward reduction was apparent in aged monkeys. Caloric restriction did ndt affect plasma GH levels in both age-groups. It appears, therefore, that long term dietary restriction can selectively affect IGF-1 levels. C1 UNIV BRESCIA,DEPT BIOMED SCI & BIOTECHNOL,BRESCIA,ITALY. NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. RI Cocchi, Daniela/G-4218-2010 NR 15 TC 7 Z9 7 U1 0 U2 0 PU BRAIN RESEARCH PROMOTION, PI LONDON PA 10 DEENA CLOSE, QUEENS DRIVE, LONDON, ENGLAND W3 OHR SN 0172-780X J9 NEUROENDOCRINOL LETT JI Neuroendocrinol. Lett. PD JUL-SEP PY 1995 VL 17 IS 3 BP 181 EP 186 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA RX065 UT WOS:A1995RX06500002 ER PT J AU VICARIOABEJON, C JOHE, KK HAZEL, TG COLLAZO, D MCKAY, RDG AF VICARIOABEJON, C JOHE, KK HAZEL, TG COLLAZO, D MCKAY, RDG TI FUNCTIONS OF BASIC FIBROBLAST GROWTH-FACTOR AND NEUROTROPHINS IN THE DIFFERENTIATION OF HIPPOCAMPAL-NEURONS SO NEURON LA English DT Article ID NERVOUS-SYSTEM; PRECURSOR CELLS; SENSORY NEURONS; RAT HIPPOCAMPUS; PROGENITOR-CELL; RECEPTOR GENE; CULTURE; PROLIFERATION; EXPRESSION; SURVIVAL AB Restrictions in neuronal fate occur during the transition from a multipotential to a postmitotic cell. This and later steps in neuronal differentiation are determined by extracellular signals. We report that basic fibroblast growth factor is mitogenic for stem cells and is a differentiation factor for calbindin-expressing hippocampal neurons. The neurotrophin NT-3 is a differentiation factor for the same neurons but does not affect proliferation. NT-3 and brain-derived neurotrophic factor promote the maturation of neurons derived from stem cells that have been grown in vitro. These results define functions for basic fibroblast growth factor and neurotrophins in the differentiation processes that direct a multipotential stem cell to a specific neuronal fate. RP VICARIOABEJON, C (reprint author), NINDS,MOLEC BIOL LAB,BLDG 36,RM 3D02,36 CONVENT DR,BETHESDA,MD 20892, USA. NR 57 TC 254 Z9 259 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1995 VL 15 IS 1 BP 105 EP 114 DI 10.1016/0896-6273(95)90068-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA RL756 UT WOS:A1995RL75600013 PM 7619514 ER PT J AU MACCAFERRI, G MCBAIN, CJ AF MACCAFERRI, G MCBAIN, CJ TI PASSIVE PROPAGATION OF LTD TO STRATUM ORIENS-ALVEUS INHIBITORY NEURONS MODULATES THE TEMPOROAMMONIC INPUT TO THE HIPPOCAMPAL CA1 REGION SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; LACUNOSUM-MOLECULARE INTERNEURONS; PYRAMIDAL CELLS; AREA CA1; RAT; DEPRESSION; SLICES; STIMULATION; RECORDINGS; CA1-REGION AB Excitatory synaptic activity in horizontal stratum oriens-alveus interneurons (OAIs) is driven by the recurrent collaterals of CA1 pyramidal cells and is strongly influenced by protocols that elicit synaptic plasticity in these principal neurons. Induction of LTD in the Schaffer collateral-CA1 pyramidal neuron synapse causes a passive down-regulation of stratum radiatum-evoked excitatory synaptic responses onto OAIs. In addition, we show that the strength of the temporoammonic input to the CA1 pyramidal neuron distal dendrites is regulated by OAI activity. The passive propagation of LTD to OAIs consequently disinhibits the direct entorhinal cortex-CA1 input, resulting in an enhanced excitation of CA1 pyramidal neurons by a mechanism not requiring activation of the trisynaptic pathway. RP MACCAFERRI, G (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,CELLULAR & SUNAPT PHYSIOL UNIT,BETHESDA,MD 20892, USA. NR 40 TC 123 Z9 123 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1995 VL 15 IS 1 BP 137 EP 145 DI 10.1016/0896-6273(95)90071-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA RL756 UT WOS:A1995RL75600016 PM 7619518 ER PT J AU KOHLER, MF BERKHOLZ, A RISINGER, JI ELBENDARY, A BOYD, J BERCHUCK, A AF KOHLER, MF BERKHOLZ, A RISINGER, JI ELBENDARY, A BOYD, J BERCHUCK, A TI MUTATIONAL ANALYSIS OF THE ESTROGEN-RECEPTOR GENE IN ENDOMETRIAL CARCINOMA SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BREAST-CANCER; EXON; DNA AB Objective: To determine whether mutation in the DNA of the estrogen-receptor gene occurs in endometrial cancer. Methods: Polymerase chain reaction amplification and single-stranded conformation polymorphism analysis of the entire coding region (exons 1-8) of the human estrogen-receptor gene, as well as an untranslated region (exon 1*) in the gene, were performed on genomic DNA extracted from 56 snap-frozen endometrial cancers. All cancers demonstrating mobility shifts on single-stranded conformation polymorphism suggestive of DNA sequence alteration were subjected to definitive DNA sequencing of the relevant portion of the estrogen-receptor gene. Results: In addition to detecting a frequent, previously described polymorphism in exon 1, single-stranded conformation polymorphism analysis of the 56 endometrial cancers identified seven cancers with mobility shifts. Three cancers shifted in exon 3, one cancer each shifted in exons 4 and 7, and two shifted in exon 8. Deoxyribonucleic acid sequencing revealed sequence alterations in all seven cases demonstrating mobility shifts. In six of these seven cases, these alterations were consistent with infrequent silent polymorphisms; in the seventh cancer, the sequence alteration proved to be a somatic missense mutation at codon 537 in the region of the estrogen-receptor gene encoding the hormone-binding domain of the receptor protein. Conclusion: The infrequent DNA mutation in the estrogen-receptor gene is unlikely to account for the variation in estrogen-receptor expression observed in endometrial cancer. C1 DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. NIEHS,RES TRIANGLE PK,NC 27709. NR 21 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 1995 VL 86 IS 1 BP 33 EP 37 DI 10.1016/0029-7844(95)00113-6 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RE544 UT WOS:A1995RE54400006 PM 7784019 ER PT J AU YU, JJ REED, E AF YU, JJ REED, E TI PRELIMINARY-STUDY OF THE EFFECT OF SELECTED CHINESE NATURAL DRUGS ON HUMAN OVARIAN-CANCER CELLS SO ONCOLOGY REPORTS LA English DT Article DE HARRINGTONINE; RABDOSIA RUBESCENS HARA; COLONY FORMATION ASSAY; OVARIAN CANCER CELLS AB This study investigated the in vitro anti-cancer effects of four Chinese natural drugs on the human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780/CP70 (cisplatin-resistant). Cells were treated with series of concentrations of drug preparations for 24 h. Vincristine prepared by the same pharmaceutical firm in China; was used as an internal control. As assessed by colony formation assays, harringtonine induced similar growth inhibiting effects in A2780 and A2780/CP70 cell lines with a 50% inhibitory dose (IC50) of 0.195 mu g/ml in both. Rabdosia rubescens Hara demonstrated a cytotoxic effect on cisplatin-sensitive A2780 cells with an IC50 of 0.58 mg/ml; but there was no effect on A2780/CP70 cells. The data suggest direct anti-proliferative activity for at least two Chinese natural medicines used in the clinical treatment of cancer in China. Further investigation of Chinese natural medicines may be valuable in the identification of new and effective anti-cancer drugs with minimal side effects. C1 NCI,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 0 U2 0 PU NATL HELLENIC RES FOUNDATION PI ATHENS PA C/O D A SPANDIDOS 48 VAS CONSTANTINOU AVE, ATHENS 11635, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUL-AUG PY 1995 VL 2 IS 4 BP 571 EP 575 PG 5 WC Oncology SC Oncology GA RC519 UT WOS:A1995RC51900016 PM 21597778 ER PT J AU SHOEMAKER, RH BALASCHAK, MS ALEXANDER, MR BOYD, MR AF SHOEMAKER, RH BALASCHAK, MS ALEXANDER, MR BOYD, MR TI THERAPEUTIC ACTIVITY OF 9-CHLORO-2-METHYLELLIPTICINIUM ACETATE IN AN ORTHOTOPIC MODEL OF HUMAN BRAIN CANCER SO ONCOLOGY REPORTS LA English DT Article DE BRAIN TUMORS; XENOGRAFTS; 9-CHLORO-2-METHYLELLIPTICINIUM ACETATE ID TUMOR-CELL-LINES; PHASE-II AB A series of ellipticinium derivatives with selective cytotoxicity towards brain tumor cell lines has been identified through in vitro screening against disease-oriented panels of human tumor cell lines. Unfortunately 9-methoxy-2-methylellipticinium, the lead compound of this series, has shown only very limited evidence for in vivo activity when examined in a variety of human tumor xenograft models. This lack of activity has been postulated to be due to metabolism. To address this issue, a derivative was synthesized which was blocked at the theoretically vulnerable 9-position and yet could be shown to retain brain tumor selectivity in vitro. In vivo xenograft testing was performed to assess the therapeutic potential of this second generation compound. To maintain continuity with the in vitro screening data, in vivo experimental therapeutic models were devised employing one of the in vitro sensitive cell lines, the U-251 glioblastoma. Cells were cultivated in vitro and injected into female athymic nude mice for therapeutic studies. The 9-chloro-derivative of the lead compound produced growth delay of subcutaneously implanted tumor cells when. administered by seven-day continuous infusion. Based on this evidence for activity in a systemic chemotherapy mode, further studies were conducted using an orthotopic brain cancer model. In three separate experiments, intracranial implantation of 1x10(7) tumor cells resulted in 100% mortality of control mice with median survival ranging from 15-18.5 days. In all experiments, mice treated by subcutaneous infusion with 9-chloro-2-methylellipticinium acetate showed increases in survival. Statistically significant effects and individual long-term survivors were observed in two experiments; These results provide support for the further preclinical development of 9-chloro-2-methylellipticinium acetate as a candidate for clinical trials against human brain cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. RP SHOEMAKER, RH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702, USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU NATL HELLENIC RES FOUNDATION PI ATHENS PA C/O D A SPANDIDOS 48 VAS CONSTANTINOU AVE, ATHENS 11635, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUL-AUG PY 1995 VL 2 IS 4 BP 663 EP 667 PG 5 WC Oncology SC Oncology GA RC519 UT WOS:A1995RC51900033 PM 21597795 ER PT J AU LASA, MSM DATILES, MB FREIDLIN, V AF LASA, MSM DATILES, MB FREIDLIN, V TI POTENTIAL VISION TESTS IN PATIENTS WITH CATARACTS SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT ARVO Annual Meeting CY MAY, 1994 CL SARASOTA, FL SP ARVO ID POSTOPERATIVE VISUAL-ACUITY; PREDICTION AB Purpose: To determine the limits of usefulness of the potential acuity meter (PAM) and the laser interferometer (LI) in determining potential visual acuity in various severities and types of cataracts. Methods: The study included 48 patients (67 eyes) who were undergoing cataract surgery and who had PAM and LI tests. The 67 eyes were grouped into (1) eyes with cataracts only (45 eyes) and (2) eyes with cataracts and other ocular diseases (22 eyes). Group 1 eyes were subdivided into two groups according to their Lens Opacities Classification System II (LOGS II) grading: la eyes (moderate cataracts) had an LOGS II grade of nuclear opalescence (NO) < 4 and cortical opacity (C) < 5 and posterior subcapsular cataract (P) < 4, and group Ib eyes (severe cataracts) had an LOGS II grade of NO = 4 or C = 5 or P = 4. The accuracy of the PAM and LI was estimated separately for each group. Results: For moderate cataracts, the accuracy of the PAM was 100% and of the LI was 92%. For severe cataracts, the accuracy of the PAM was 52% and of the LI was 79%. Both instruments tended to underestimate visual outcome more in eyes with posterior subcapsular cataracts. For eyes with other ocular diseases, the LI tends to overestimate the probable visual outcome more than the PAM, especially in patients with poor retinal function. Conclusions: Several factors such as preoperative visual acuity of 20/200 or worse, the type and severity of the cataract, and coexisting retinal disorders may affect the accuracy of the PAM and LI tests, and these should be considered when interpreting predicted vision, especially in preoperative counseling of patients. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 7 TC 18 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1995 VL 102 IS 7 BP 1007 EP 1011 PG 5 WC Ophthalmology SC Ophthalmology GA RK251 UT WOS:A1995RK25100006 PM 9121743 ER PT J AU HEIMDAHL, A FOX, PC PETERSON, DE AF HEIMDAHL, A FOX, PC PETERSON, DE TI CANCER THERAPIES FOR THE 21ST-CENTURY - 9TH ANNUAL-MEETING OF THE INTERNATIONAL-SOCIETY-FOR-ORAL-ONCOLOGY, 2-4 JUNE 1994, NATIONAL-INSTITUTES-OF-HEALTH, BETHESDA, MARYLAND, USA SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Editorial Material C1 UNIV CONNECTICUT,CTR HLTH,SCH DENT MED,DEPT ORAL DIAG,FARMINGTON,CT 06030. KAROLINSKA INST,DEPT ORAL SURG,S-14104 STOCKHOLM,SWEDEN. NIDR,CLIN INVEST & PATIENT CARE BRANCH,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 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD JUL PY 1995 VL 31B IS 4 BP 286 EP 287 PG 2 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA RW741 UT WOS:A1995RW74100015 ER PT J AU BECK, JC MCCLATCHEY, KD LESPERANCE, MM ESCLAMADO, RM CAREY, TE BRADFORD, CR AF BECK, JC MCCLATCHEY, KD LESPERANCE, MM ESCLAMADO, RM CAREY, TE BRADFORD, CR TI PRESENCE OF HUMAN PAPILLOMAVIRUS PREDICTS RECURRENCE OF INVERTED PAPILLOMA SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 18-21, 1994 CL SAN DIEGO, CA SP Amer Acad Otolaryngol Head & Neck Surg ID SQUAMOUS-CELL CARCINOMA; PARANASAL SINUSES; NASAL CAVITY; SCHNEIDERIAN PAPILLOMAS; INSITU HYBRIDIZATION; DNA; ANTIGENS; LESIONS AB Recent evidence suggests that human papillomavirus may play a role in the pathogenesis of inverted papilloma, a benign but locally aggressive neoplasm with a high recurrence rate and an association with squamous cell carcinoma. Histologic features of inverted papilloma have not been useful in discriminating lesions at high risk for recurrence. We studied archival pathology specimens from 32 patients with inverted papilloma treated at the University of Michigan between 1980 and 1994 with polymerase chain reaction techniques and human papillomavirus E6 and L1 consensus primers. Twenty (63%) specimens tested positive for human papillomavirus. The clinical status of the remaining 25 patients was reviewed after seven patients with recent diagnosis or who were lost to follow-up were excluded. A significant association was identified between the presence of human papillomavirus DNA in inverted papilloma and recurrence after surgical excision. Thirteen of 15 patients whose tumors tested positive for HPV recurred, whereas none of the 10 patients whose tumors were human papillomavirus negative recurred (p < 0.00002). This strongly suggests that the presence of human papillomavirus predicts recurrence of inverted papilloma. C1 UNIV MICHIGAN,DEPT OTOLARYNGOL HEAD & NECK SURG,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. NIDOCD,GENET MOLEC LAB,BETHESDA,MD. OI Carey, Thomas/0000-0002-5202-7518 NR 27 TC 44 Z9 48 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 1995 VL 113 IS 1 BP 49 EP 55 DI 10.1016/S0194-5998(95)70144-3 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RH255 UT WOS:A1995RH25500008 PM 7603721 ER PT J AU CHANG, AC ATIGA, WL MCAREAVEY, D FANANAPAZIR, L AF CHANG, AC ATIGA, WL MCAREAVEY, D FANANAPAZIR, L TI RELIEF OF LEFT-VENTRICULAR OUTFLOW TRACT OBSTRUCTION FOLLOWING INADVERTENT LEFT-VENTRICULAR APICAL PACING IN A PATIENT WITH HYPERTROPHIC CARDIOMYOPATHY SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Note DE HYPERTROPHIC CARDIOMYOPATHY; PACING AB Dual chamber (DDD) pacing improves symptoms and relieves left ventricular (LV) outflow obstruction in hypertrophic cardiomyopathy. The ventricular lead is usually positioned at the right ventricular apex (RVA). We report a patient in whom the ventricular lead had inadvertently penetrated the septum, resulting in DDD pacing from the LV apex. However, after 3 months, obstruction was reduced and symptoms were improved. Pacing from LV apex and RVA resulted in comparable hemodynamic improvement. This case suggests that the asynchronous wave of septal contraction, originating from the apex, irrespective of ventricular site, accounts for the reduction in LV outflow obstruction. C1 NHLBI,INHERITED CARDIOVASC DIS SECT,CARDIOL BRANCH,BETHESDA,MD 20892. NR 3 TC 9 Z9 9 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 1995 VL 18 IS 7 BP 1450 EP 1454 DI 10.1111/j.1540-8159.1995.tb02609.x PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA RG605 UT WOS:A1995RG60500016 PM 7567600 ER PT J AU BUEKENS, P WILCOX, AJ KIELY, J MASUYSTROOBANT, G AF BUEKENS, P WILCOX, AJ KIELY, J MASUYSTROOBANT, G TI BIRTH-WEIGHT, PRETERM BIRTHS AND NEONATAL-MORTALITY IN BELGIUM AND THE UNITED-STATES SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID PERINATAL-MORTALITY; WEIGHT AB Belgium is known to have a lesser low birthweight rate and a lower infant mortality rate than the United States. We used previously unpublished data to show that beneath this comparison lies a more complicated picture. Singleton live birth certificates for 1986-87 were analysed. Despite a lower mean birthweight in Belgium (3360 g) than in the United States (3420 g), Belgium had fewer (4.9%) low birthweight infants than the US (5.9%) because of fewer preterm births (4.4 vs. 9.3%). Consistent with the excess of preterm births in the US, the residual distribution of birthweight was smaller in Belgium (2.2% vs. 3.1%). Whereas neonatal mortality was 4.8/1000 in Belgium and 5.6/1000 in the US, birthweight-specific neonatal mortality was higher in Belgium. The challenge for Belgium is to improve the survival of newborns regardless of their birthweight. In the US, the task is to eliminate the excess of small preterm infants. C1 NATL INST ENVIRONM HLTH SCI,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. CATHOLIC UNIV LEUVEN,INST DEMOG,LOUVAIN,BELGIUM. RP BUEKENS, P (reprint author), FREE UNIV BRUSSELS,SCH PUBL HLTH,808 ROUTE LENNIK,B-1070 BRUSSELS,BELGIUM. OI Wilcox, Allen/0000-0002-3376-1311 NR 23 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 1995 VL 9 IS 3 BP 273 EP 280 DI 10.1111/j.1365-3016.1995.tb00143.x PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA RH869 UT WOS:A1995RH86900005 PM 7479276 ER PT J AU TRYGG, K LUNDLARSEN, K SANDSTAD, B HOFFMAN, HJ JACOBSEN, G BAKKETEIG, LS AF TRYGG, K LUNDLARSEN, K SANDSTAD, B HOFFMAN, HJ JACOBSEN, G BAKKETEIG, LS TI DO PREGNANT SMOKERS EAT DIFFERENTLY FROM PREGNANT NONSMOKERS SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID SMOKING; NONSMOKERS; DIET; WOMEN; RISK AB This article describes a study of the relationship between diet and smoking in a group of 821 Norwegian pregnant women. The study is part of a multi-centre project, examining risk factors for intrauterine growth retardation. Two 3-day dietary records were collected during the 17th and 33rd week of pregnancy. Information on smoking habits and other relevant parameters were collected through an extensive questionnaire. The results showed that the smokers consumed significantly less than the non-smokers of bread, cakes and cookies, vegetables, fruits and berries, cheese, yoghurt, low fat milk, juice and tea. The smokers also consumed significantly more meat, margarine, whole milk, soft drinks and coffee than the non-smokers on both occasions. The diet of the smokers contained significantly less protein, carbohydrate, dietary fibre, thiamin, riboflavin, vitamin C, calcium and iron as compared with the non-smokers. Fat contributed significantly more to the energy content of the diet of the smokers and it is concluded that their diet was less nutritious than that of the non-smokers throughout pregnancy. C1 NIDOCD,BETHESDA,MD. UNIV TRONDHEIM,DEPT COMMUNITY MED & GEN PRACICE,TRONDHEIM,NORWAY. RP TRYGG, K (reprint author), UNIV OSLO,INST NUTR RES,DIETARY RES SECT,POB 1117 BLINDERN,N-0317 OSLO,NORWAY. FU NICHD NIH HHS [N01-HD-4-2803] NR 26 TC 41 Z9 41 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 1995 VL 9 IS 3 BP 307 EP 319 DI 10.1111/j.1365-3016.1995.tb00147.x PG 13 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA RH869 UT WOS:A1995RH86900008 PM 7479279 ER PT J AU READ, JS CLEMENS, JD AF READ, JS CLEMENS, JD TI LOW-BIRTH-WEIGHT AS A DETERMINANT OF INFECTIOUS-DISEASE MORTALITY - A METHODOLOGICAL EVALUATION SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID URBAN BRAZILIAN CHILDREN; BREAST-FEEDING DURATION; SOUTHERN BRAZIL; BIRTH-WEIGHT; INFANT-MORTALITY; GROWTH; DIARRHEA; INTERVENTIONS; HEALTH; DEATHS AB Low birthweight (LBW) is cited as an important determinant of infectious disease mortality during infancy, both in developed and developing countries. We applied methodological standards to evaluate the scientific validity and clinical applicability of epidemiological studies of this relationship. Three published studies, all reporting an elevation of the risk of infectious disease mortality in infants born with LBW, were identified. Noteworthy methodological deficiencies found in one or more studies included failure to obtain objective data about birthweight and gestational age for a high proportion of study subjects, lack of explicit criteria for assigning causes of death, failure to safeguard against biases in assessment of cause of death and inadequate control for potential confounding variables. In addition, clinical application of the results of these studies was limited by lack of exploration of the roles of preterm birth vs. small-for-gestational-age (SGA) birth, as well as by inattention to the role of congenital anomalies, in explaining the elevated risk. Although our evaluation does not necessarily negate the results of these studies, the failure of any of the studies to comply with all of the standards highlights the need for further research to provide credible evidence regarding the presence and strength of a relationship between LBW and infectious disease mortality in both developed and developing countries. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NR 42 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 1995 VL 9 IS 3 BP 351 EP 362 DI 10.1111/j.1365-3016.1995.tb00152.x PG 12 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA RH869 UT WOS:A1995RH86900012 PM 7479283 ER PT J AU STEWART, GR ELSON, L ARAUJO, E GUDERIAN, R NUTMAN, TB BRADLEY, JE AF STEWART, GR ELSON, L ARAUJO, E GUDERIAN, R NUTMAN, TB BRADLEY, JE TI ISOTYPE-SPECIFIC CHARACTERIZATION OF ANTIBODY-RESPONSES TO ONCHOCERCA-VOLVULUS IN PUTATIVELY IMMUNE INDIVIDUALS SO PARASITE IMMUNOLOGY LA English DT Article DE ONCHOCERCIASIS; FILARIASIS; IMMUNITY; ANTIBODY RESPONSE ID GUATEMALAN HUMAN ONCHOCERCIASIS; HUMAN FILARIASIS; INFECTION; IGE; RECOGNITION; ANTIGENS; QUANTITATION; PROTEINS; IGG4 AB Isotype/subclass-specific antibody responses to adult Onchocerca volvulus extract (OvAg) were assessed by both ELISA and immunoblotting for a group of putatively immune individuals (PIs, n = 29) from a hyperendemic area in Ecuador and for a group of infected individuals (INFs, n = 47) front the same region. As a group, the Pls have been previously shown to possess lower levels of OvAg specific IgG1, IgG2, IgG3 and IgG4 than INFs but semiquantitative analysis revealed that the relative proportions of these subclasses differs between the two groups. The IgG of the PI group contained a higher proportion of IgG3 and a lower proportion of IgG4 than the INF group. The frequency distribution of IgG3 responses was similar for the PI and INF groups. The frequency distributions for IgG1, IgG4 and IgE were significantly different between the PI and INF groups. A subgroup of the Pls were identified from frequency distributions and multivariate plots of individual isotype responses as having antibody responses (mainly IgG4) possibly indicative of cryptic infection. High IgE responses were exclusive to INF individuals, and a rare response type of high IgG3 with negligible levels of other isotypes/subclasses was seen only in the PI group. However, the majority of the Pls had negligible responses for all antibody classes. Immunoblots demonstrated no obvious differences in qualitative recognition between the PIs and INFs. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HOSP VOZANDES,INVEST CLIN,QUITO,ECUADOR. RP STEWART, GR (reprint author), UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOL,PRINCE CONSORT RD,LONDON SW7 2BB,ENGLAND. OI Bradley, Janette/0000-0003-3973-7977 NR 30 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD JUL PY 1995 VL 17 IS 7 BP 371 EP 380 DI 10.1111/j.1365-3024.1995.tb00904.x PG 10 WC Immunology; Parasitology SC Immunology; Parasitology GA RP168 UT WOS:A1995RP16800006 PM 8552410 ER PT J AU WILLINGER, M AF WILLINGER, M TI SIDS PREVENTION SO PEDIATRIC ANNALS LA English DT Article RP WILLINGER, M (reprint author), NICHHD,CRMC,PPB,9000 ROCKVILLE PIKE,BLDG 6100,RM 4B03,BETHESDA,MD 20892, USA. NR 0 TC 21 Z9 22 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD JUL PY 1995 VL 24 IS 7 BP 358 EP 364 PG 7 WC Pediatrics SC Pediatrics GA RH327 UT WOS:A1995RH32700004 PM 7567180 ER PT J AU BERLIN, CM GORMAN, RL MAY, DG NOTTERMAN, DA WEISMANN, DN WILSON, GS WILSON, JT BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ BANNER, W AF BERLIN, CM GORMAN, RL MAY, DG NOTTERMAN, DA WEISMANN, DN WILSON, GS WILSON, JT BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ BANNER, W TI TREATMENT GUIDELINES FOR LEAD-EXPOSURE IN CHILDREN SO PEDIATRICS LA English DT Note ID CHELATION-THERAPY; 2,3-DIMERCAPTOSUCCINIC ACID; PENICILLAMINE; MOBILIZATION; MANAGEMENT; EFFICACY; INTOXICATION; PATIENT; HUMANS; CAEDTA C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. DEPT HLTH & WELF,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RP BERLIN, CM (reprint author), AMER MED ASSOC,CHICAGO,IL 60610, USA. NR 43 TC 51 Z9 53 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1995 VL 96 IS 1 BP 155 EP 160 PN 1 PG 6 WC Pediatrics SC Pediatrics GA RH182 UT WOS:A1995RH18200030 ER PT J AU CHIGNELL, CF SIK, RH AF CHIGNELL, CF SIK, RH TI MAGNETIC-FIELD EFFECTS ON THE PHOTOHEMOLYSIS OF HUMAN ERYTHROCYTES BY KETOPROFEN AND PROTOPORPHYRIN-IX SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Note ID CELLS AB Application of a static external magnetic field (3350 G) during UV-irradiation (>300 nm) reduced the time for 50% photohemolysis of human erythrocytes by the phototoxic drug ketoprofen (3-benzoyl-alpha-methylbenzoacetic acid) from 96 min to 78 min. This observation can be attributed to a magnetic field induced decrease in the rate of intersystem crossing (k(ISC)) of the geminate tripler radical pair generated by the reduction of ketoprofen in its triplet excited stare by erythrocyte membrane constituents, probably lipids. The decrease in k(ISC) results in an increase in the concentration and/or lifetime of free radicals that escape from the triplet radical pair. Thus the critical radical concentration needed to cause membrane damage and cell lysis is reached sooner in the presence of the magnetic field. In contrast, the photohemolysis induced by the photodynamic agent protoporphyrin IX was not affected by the magnetic field. Protoporphyrin IX photohemolysis, which is initiated by singlet oxygen, does not involve the initial generation of a triplet radical pair and so is not influenced by the magnetic field. The enhancement of ketoprofen-induced photohemolysis by an externally applied magnetic field is the first example of a magnetic field effect on a toxicological process involving free radicals. RP CHIGNELL, CF (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1995 VL 62 IS 1 BP 205 EP 207 DI 10.1111/j.1751-1097.1995.tb05260.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RJ710 UT WOS:A1995RJ71000030 PM 7638268 ER PT J AU CHALLIS, JRG ANDRES, SF CATZ, CS FISHER, SJ HAY, WW HUNT, JS ILLSLEY, NP THORNBURG, KL AF CHALLIS, JRG ANDRES, SF CATZ, CS FISHER, SJ HAY, WW HUNT, JS ILLSLEY, NP THORNBURG, KL TI CONFERENCE REPORT - PLACENTAL GROWTH AND FUNCTION SO PLACENTA LA English DT Editorial Material C1 NICHHD,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT STOMATOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ORAL BIOL,SAN FRANCISCO,CA 94143. UNIV COLORADO,SCH MED,DEPT PEDIAT,DENVER,CO 80262. UNIV KANSAS,MED CTR,DEPT ANAT & CELL BIOL,KANSAS CITY,KS 66160. UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143. OREGON HLTH SCI UNIV,DEPT PHYSIOL,PORTLAND,OR 97201. RP CHALLIS, JRG (reprint author), UNIV WESTERN ONTARIO,LAWSON RES INST,LONDON,ON,CANADA. RI Challis, John/E-7419-2014 NR 1 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD JUL PY 1995 VL 16 IS 5 BP 471 EP 473 DI 10.1016/0143-4004(95)90106-X PG 3 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA RK947 UT WOS:A1995RK94700008 PM 7479619 ER PT J AU COTE, TR OBRIEN, TR WARD, JW WILSON, SE BLATTNER, WA AF COTE, TR OBRIEN, TR WARD, JW WILSON, SE BLATTNER, WA TI AIDS AND CANCER REGISTRY LINKAGE - MEASUREMENT AND ENHANCEMENT OF REGISTRY COMPLETENESS SO PREVENTIVE MEDICINE LA English DT Article AB Background and methods. To measure AIDS registry completeness for Kaposi's sarcoma (KS) and cancer registry completeness for KS and non-Hodgkin's lymphoma (NHL), we linked AIDS and cancer registries at selected health departments. Results. We found 10,350 people with KS: 1,935 reported only to the AIDS registry, 1,428 reported only to the cancer registry, and 6,987 reported to both. Ninety-three cases of non-HIV-associated KS were expected. For KS, AIDS registry completeness was 84% [6,987/(6,987 + 1,428 - 93)] and cancer registry completeness was 78% [6,987/(6,987 + 1,935)]. Cancer registry completeness for AIDS-related NHL was 76%. Conclusion. If this linking were conducted nationally, about 5,700 additional cases of AIDS and 10,000 additional cases of AIDS-related cancers would be recorded. (C) 1995 Academic Press, Inc. C1 CTR DIS CONTROL & PREVENT,DIV HIV AIDS,DIV SURVEILLANCE,ATLANTA,GA 30341. ATLANTIC RES CORP,ROCKVILLE,MD. RP COTE, TR (reprint author), NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL BRANCH,EPN-343,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 9 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1995 VL 24 IS 4 BP 375 EP 377 DI 10.1006/pmed.1995.1061 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA RM398 UT WOS:A1995RM39800009 PM 7479628 ER PT J AU NEWMAN, JD FARLEY, MJ AF NEWMAN, JD FARLEY, MJ TI AN ETHOLOGICALLY BASED, STIMULUS AND GENDER-SENSITIVE NONHUMAN PRIMATE MODEL FOR ANXIETY SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE ALARM; SEPARATION; SQUIRREL MONKEY; VOCALIZATION ID ADULT SQUIRREL-MONKEYS; INFANT RHESUS-MONKEYS; SEPARATION DISTRESS; BEHAVIOR AB 1. Adult male and female squirrel monkeys were tested for behavioral responses to 5 min. social separation (alone in test room) followed by 30-sec. exposure to 2 humans wearing a leather capture glove. 2. Trials were preceded by intramuscular injection of an anticholinergic drug, benactyzine hydrochloride, in doses of 0.0, 0.6, 1.0, 2.0, and 3.0 mg/kg. 3. Measured behaviors were number and type of vocalization and locomotor activity (duration in sec) in each of the two testing conditions. 4. A dose-response relationship for bark/yap vocalizations during the 30-sec trials was established, with 1.0 mg/kg being the most effective dose. 5. Males and females differed in the number of barks/yaps produced during 30-sec. trials at every drug dose. 6. The present testing paradigm provides the basis for efficiently determining the extent of gender differences in dose/response relationships for drugs of possible therapeutic value in the treatment of anxiety-related behavioral disorders. RP NEWMAN, JD (reprint author), NICHHD,CTR ANIM,COMPARAT ETHOL LAB,BLDG 112,POB 529,POOLESVILLE,MD 20837, USA. NR 17 TC 9 Z9 9 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL PY 1995 VL 19 IS 4 BP 677 EP 685 DI 10.1016/0278-5846(95)00111-8 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RV424 UT WOS:A1995RV42400011 PM 8588065 ER PT J AU CARTER, HB PEARSON, JD METTER, EJ CHAN, DW ANDRES, R FOZARD, JL ROSNER, W WALSH, PC AF CARTER, HB PEARSON, JD METTER, EJ CHAN, DW ANDRES, R FOZARD, JL ROSNER, W WALSH, PC TI LONGITUDINAL EVALUATION OF SERUM ANDROGEN LEVELS IN MEN WITH AND WITHOUT PROSTATE-CANCER SO PROSTATE LA English DT Article DE HORMONES; ANDROGENS; PROSTATE CANCER ID TESTOSTERONE; HORMONES; RISK; HYPERPLASIA; PROTEINS; JAPANESE; DISEASE; BLACK; WHITE; RATS AB Androgens are thought to play a role in the pathogenesis of prostate cancer. We evaluated androgen levels in 3 age-matched groups of men who were part of the Baltimore Longitudinal Study of Aging: 1) 16 men with no prostatic disease by urologic history and exam (control group); 2) 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and 3) 20 men with a histologic diagnosis of prostate cancer (16 with local/regional cancer, and 4 with metastatic cancer). Luteinizing hormone (LH), total testosterone (T), and free T were measured on stored AM sera by radioimmunoassay (RIA). Free T was also calculated from the measured concentrations of total T and sex hormone binding globulin (SHBG). The median number of repeated sex steroid measurements ranged from 6-9 over a period from 7-25 years prior to the diagnosis of prostate disease. There were no significant differences in age-adjusted LH, total T, SHBG, or calculated free T levels among the groups at 0-5, 5-10, and 10-15 years before diagnosis. These data suggest that there are no measurable differences in serum testosterone levels among men who are destined to develop prostate cancer and those without the disease. (C) 1995 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT LAB MED,BALTIMORE,MD 21287. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. ROOSEVELT HOSP,DIV ENDOCRINOL,NEW YORK,NY. RP CARTER, HB (reprint author), JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,403 MARBURG,BALTIMORE,MD 21287, USA. RI Fozard, James Leonard/B-3660-2009; Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 19 TC 83 Z9 86 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 0270-4137 J9 PROSTATE JI Prostate PD JUL PY 1995 VL 27 IS 1 BP 25 EP 31 DI 10.1002/pros.2990270106 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA RR558 UT WOS:A1995RR55800005 PM 7541528 ER PT J AU BORK, P HOLM, L KOONIN, EV SANDER, C AF BORK, P HOLM, L KOONIN, EV SANDER, C TI THE CYTIDYLYLTRANSFERASE SUPERFAMILY - IDENTIFICATION OF THE NUCLEOTIDE-BINDING SITE AND FOLD PREDICTION SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE HOMOLOGY SEARCH; PHOSPHODIESTERASES; SEQUENCE ANALYSIS; STRUCTURE PREDICTION; THREADING ID TRANSFER-RNA-SYNTHETASE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SACCHAROMYCES-CEREVISIAE; PROTEIN STRUCTURES; ALIGNMENT; CLONING; HOMOLOGY; REGION; MODEL AB The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved, Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes, We predict that TagD is a member of this family, The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyl-tRNA synthetases, The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the alpha/beta topography of the class I aminoacyl-tRNA synthetases, The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template, The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site, If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily. (C) 1995 Wiley-Liss, Inc. C1 MAX DELBRUCK CTR MOLEC MED,D-13125 BERLIN,GERMANY. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP BORK, P (reprint author), EUROPEAN MOLEC BIOL LAB,PROT DESIGN GRP,MEYERHOFSTR 1,D-69012 HEIDELBERG,GERMANY. RI sander, chris/H-1452-2011; Bork, Peer/F-1813-2013; Zhang, Ning/F-1387-2014 OI Bork, Peer/0000-0002-2627-833X; NR 38 TC 74 Z9 76 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD JUL PY 1995 VL 22 IS 3 BP 259 EP 266 DI 10.1002/prot.340220306 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RL378 UT WOS:A1995RL37800005 PM 7479698 ER PT J AU WINOKUR, G CORYELL, W ENDICOTT, J AKISKAL, H KELLER, M MASER, JD WARSHAW, M AF WINOKUR, G CORYELL, W ENDICOTT, J AKISKAL, H KELLER, M MASER, JD WARSHAW, M TI FAMILIAL DEPRESSION VERSUS DEPRESSION IDENTIFIED IN A CONTROL-GROUP - ARE THEY THE SAME SO PSYCHOLOGICAL MEDICINE LA English DT Article ID AFFECTIVE-DISORDER; DIAGNOSTIC CRITERIA; MAJOR DEPRESSION; RELIABILITY; HISTORY; SCALE AB Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment, This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study, Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands, Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression, They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study, In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands, Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls, Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,IOWA CITY,IA. FU NIMH NIH HHS [R01 MH025478] NR 24 TC 8 Z9 8 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 1995 VL 25 IS 4 BP 797 EP 806 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA RT072 UT WOS:A1995RT07200013 PM 7480457 ER PT J AU COWDRY, RW ALFRED, DC FOX, JC GOLDMANRAKIC, PS HAMBURG, BA JARVIS, CD MATARAZZO, JD MCGAUGH, JL SHUMWAY, DL TUCKER, GJ STRETE, C VARMUS, RT SCARAMOZZINO, JA SHALALA, DE BORNEMANN, TH BOWER, GH JACKSON, JS BIEDERMAN, I CARPENTER, P CONGER, R GALLISTEL, CR GOLDSMITH, HH HOUSE, J KIHLSTROM, JF JONES, JM KAHNEMAN, D LEVENSON, RW ROVEECOLLIER, C RUBLE, D SNOWDON, C ALBERTS, J CAUCE, AM CLARK, M CUTRONA, C DEWAAL, F EAGLY, A EMDE, R FUNDER, D GARDNER, H GELMAN, S GOOD, B HARACKIEWICZ, J HARTER, S HIGGINS, ET HOLYOAK, K KITAYAMA, S LOFTUS, E MCCLINTOCK, M MCLANAHAN, S MENAGHAN, E MINEKA, S NEWPORT, E POSNER, M RESCORLA, R ROSS, CE SATINOFF, E SCHACTER, D SEIDENBERG, M KOSLOW, SH OLIVERI, ME COCKING, RR HANN, DM SHERMAN, SJ SHINN, M STERNBERG, R SUOMI, S THELEN, E TREISMAN, A HUFFMAN, LC KURTZMAN, HS TRICKETT, EJ ROSENFELD, AH TROTTER, R AF COWDRY, RW ALFRED, DC FOX, JC GOLDMANRAKIC, PS HAMBURG, BA JARVIS, CD MATARAZZO, JD MCGAUGH, JL SHUMWAY, DL TUCKER, GJ STRETE, C VARMUS, RT SCARAMOZZINO, JA SHALALA, DE BORNEMANN, TH BOWER, GH JACKSON, JS BIEDERMAN, I CARPENTER, P CONGER, R GALLISTEL, CR GOLDSMITH, HH HOUSE, J KIHLSTROM, JF JONES, JM KAHNEMAN, D LEVENSON, RW ROVEECOLLIER, C RUBLE, D SNOWDON, C ALBERTS, J CAUCE, AM CLARK, M CUTRONA, C DEWAAL, F EAGLY, A EMDE, R FUNDER, D GARDNER, H GELMAN, S GOOD, B HARACKIEWICZ, J HARTER, S HIGGINS, ET HOLYOAK, K KITAYAMA, S LOFTUS, E MCCLINTOCK, M MCLANAHAN, S MENAGHAN, E MINEKA, S NEWPORT, E POSNER, M RESCORLA, R ROSS, CE SATINOFF, E SCHACTER, D SEIDENBERG, M KOSLOW, SH OLIVERI, ME COCKING, RR HANN, DM SHERMAN, SJ SHINN, M STERNBERG, R SUOMI, S THELEN, E TREISMAN, A HUFFMAN, LC KURTZMAN, HS TRICKETT, EJ ROSENFELD, AH TROTTER, R TI BASIC BEHAVIORAL-SCIENCE RESEARCH FOR MENTAL-HEALTH - A NATIONAL INVESTMENT - A REPORT OF THE NATIONAL-ADVISORY-MENTAL-HEALTH-COUNCIL BEHAVIORAL-SCIENCE TASK-FORCE SO PSYCHOLOGICAL SCIENCE LA English DT Editorial Material C1 MOREHOUSE SCH MED,ATLANTA,GA 30310. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. WILLIAM T GRANT FDN,NEW YORK,NY. COUNCIL DIST COLUMBIA,WASHINGTON,DC. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV CALIF IRVINE,IRVINE,CA 92717. NEW HAMPSHIRE DIV MENTAL HLTH & DEV SERV,CONCORD,NH. UNIV WASHINGTON,SEATTLE,WA 98195. NIH,BETHESDA,MD 20892. DEPT VET AFFAIRS,WASHINGTON,DC. USN,POSTGRAD SCH,MONTEREY,CA 93940. US DEPT HHS,WASHINGTON,DC 20201. SUBST ABUSE & MENTAL HLTH ADM,ROCKVILLE,MD. RP COWDRY, RW (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD JUL PY 1995 VL 6 IS 4 BP 192 EP 202 PG 11 WC Psychology, Multidisciplinary SC Psychology GA RK948 UT WOS:A1995RK94800002 ER PT J AU COWDRY, RW AF COWDRY, RW TI MESSAGE FOR THE AMERICAN-PSYCHOLOGICAL-ASSOCIATION AND THE AMERICAN-PSYCHOLOGICAL-SOCIETY SO PSYCHOLOGICAL SCIENCE LA English DT Editorial Material RP COWDRY, RW (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD JUL PY 1995 VL 6 IS 4 BP 193 EP 193 PG 1 WC Psychology, Multidisciplinary SC Psychology GA RK948 UT WOS:A1995RK94800003 ER PT J AU JOHANSON, CE MATTOX, A SCHUSTER, CR AF JOHANSON, CE MATTOX, A SCHUSTER, CR TI CONDITIONED REINFORCING EFFECTS OF CAPSULES ASSOCIATED WITH HIGH VERSUS LOW MONETARY PAYOFF SO PSYCHOPHARMACOLOGY LA English DT Article DE HUMANS; SELF-ADMINISTRATION; CONDITIONED REINFORCEMENT; CONDITIONING; SUBJECTIVE EFFECTS ID DRUG PREFERENCE; ETHANOL; VOLUNTEERS; ALCOHOL; HUMANS; MOOD; RAT AB The ability of a placebo drug capsule to serve as a conditioned reinforcer as a function of being paired with money reinforcement was evaluated. Volunteers were administered two differently colored capsules that presumably contained two different drugs. Although the volunteers were told they might contain a stimulant, sedative, or placebo, both capsules contained only a placebo. During sessions, volunteers participated in performance tasks. The tasks were programmed so that following one capsule, the amount of money obtained contingent upon responding was greater (high frequency of reinforcement) than following the other capsule (low frequency of reinforcement). During experiment 1, participants were exposed twice each to the two reinforcement conditions (sampling). During sessions 6-8, no tasks were done but participants were allowed to choose which capsule they preferred. During these choice sessions, 9 of 12 participants chose the capsule associated with the high frequency of reinforcement 2 or 3 times. Experiment 2 was designed to explore further whether the differential mood effects observed during sampling sessions could be conditioned. Although this could not be demonstrated, the self-administration results demonstrating the control of choice behavior even in the absence of pharmacological effects suggest that drugs may function as conditioned reinforcers. This finding has implications for broadening our understanding of the determinants of initiation and continued drug use. RP JOHANSON, CE (reprint author), NIDA,INTRAMURAL RES PROGRAM,ETIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1995 VL 120 IS 1 BP 42 EP 48 DI 10.1007/BF02246143 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RJ237 UT WOS:A1995RJ23700005 PM 7480534 ER PT J AU FLEISHAKER, JC GARZONE, PD CHAMBERS, JH SIROCCO, K WEINGARTNER, H AF FLEISHAKER, JC GARZONE, PD CHAMBERS, JH SIROCCO, K WEINGARTNER, H TI COMPARISON OF THE SPECTRUM OF COGNITIVE EFFECTS OF ALPRAZOLAM AND ADINAZOLAM AFTER SINGLE DOSES IN HEALTHY-SUBJECTS SO PSYCHOPHARMACOLOGY LA English DT Article DE TRIAZOLOBENZODIAZEPINE; PSYCHOMOTOR PERFORMANCE; MEMORY; ACTIVE METABOLITE; COGNITION ID IMPLICIT MEMORY; LORAZEPAM; DIAZEPAM; PHARMACOKINETICS; VOLUNTEERS; PSYCHOMOTOR; PLACEBO; SYSTEMS; PHARMACODYNAMICS; BENZODIAZEPINES AB Single doses of alprazolam (0, 0.5, 1.5 mg) or adinazolam mesylate sustained release tablets (SR) (0, 15, 45 mg) were administered to separate groups of 12 healthy men in a crossover design. Psychomotor performance was assessed by digit symbol substitution (DSST), and memory was assessed using a test battery which reflects various aspects of memory, including attention/working memory, explicit memory (recall of categorically related words), semantic memory (fragmented picture recognition, generation of category exemplars), and implicit memory (time saved in resolving fragmented pictures on the second exposure). Maximal psychomotor performance and memory decrements for the highest active doses were significantly different from placebo for all tasks at some time after dosing. The maximum decrement in DSST was not significantly different between drugs at the high dose (P = 0.288). Maximum attention/working memory decrements were significantly different between the high doses of the active compounds (P = 0.031), and the difference in maximum category recall decrement was marginally significant (P = 0.067). Access to knowledge memory was not significantly altered by these drugs; these results are similar to those obtained for other benzodiazepines. Both drugs exhibited slight effects on implicit memory. The results suggest that the sedative and memory effects of these triazolobenzodiazepines may not be closely related and suggest that adinazolam has a somewhat different spectrum of cognitive effects relative to alprazolam. C1 UNIV PITTSBURGH,SCH PHARM,CTR PHARMACODYNAM RES,PITTSBURGH,PA. NIAAA,BETHESDA,MD. RP FLEISHAKER, JC (reprint author), UPJOHN CO,CLIN PHARMACOKINET UNIT,KALAMAZOO,MI 49007, USA. NR 37 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1995 VL 120 IS 2 BP 169 EP 176 DI 10.1007/BF02246190 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RM611 UT WOS:A1995RM61100008 PM 7480549 ER PT J AU ANDERSON, DE BAGROV, AY AUSTIN, JL AF ANDERSON, DE BAGROV, AY AUSTIN, JL TI INHIBITED BREATHING DECREASES RENAL SODIUM-EXCRETION SO PSYCHOSOMATIC MEDICINE LA English DT Article DE HYPOVENTILATION; END TIDAL CO2; SODIUM; ENDOGENOUS DIGITALIS-LIKE FACTORS; BLOOD PRESSURE ID BLOOD-PRESSURE; HYPERTENSION; STRESS; HUMANS; RETENTION; DOGS; RAT AB This study tested the hypothesis that breathing at the upper end of the normal range of end tidal CO2 decreases renal sodium excretion. Normotensive human subjects learned to self-regulate end tidal CO2 using a respiratory gas monitor and feedback procedure. Urine flow rates were increased by a standardized water drinking regimen. Urinary volume and sodium and potassium excretion were decreased during 30 minutes of inhibited (i.e. high normal end tidal CO2) breathing, compared with levels preceding and after task Performance. Blood pressure, but not heart rate, increased during task performance. Plasma volume increase under these conditions is indicated by the observation that urinary excretion of an endogenous digoxin-like factor was increased. The physiological mechanism by which inhibited breathing elicits renal sodium retention remains to be determined. This breathing pattern could mediate the role of behavioral stress in some forms of hypertension. RP ANDERSON, DE (reprint author), NIA,GERONTOL RES CTR,BEHAV MED SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 1995 VL 57 IS 4 BP 373 EP 380 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA RM044 UT WOS:A1995RM04400009 PM 7480567 ER PT J AU HICKEY, CA CLIVER, SP MULVIHILL, FX MCNEAL, SF HOFFMAN, HJ GOLDENBERG, RL AF HICKEY, CA CLIVER, SP MULVIHILL, FX MCNEAL, SF HOFFMAN, HJ GOLDENBERG, RL TI EMPLOYMENT-RELATED STRESS AND PRETERM DELIVERY - A CONTEXTUAL EXAMINATION SO PUBLIC HEALTH REPORTS LA English DT Article ID LOW-BIRTH-WEIGHT; WORKING-CONDITIONS; PHYSICAL-ACTIVITY; GESTATIONAL-AGE; MATERNAL WORK; RISK-FACTORS; PREGNANCY; PREMATURITY; POPULATION; GROWTH AB Studies of employment-related stress as a risk factor for preterm delivery suggest that contextual factors unrelated to occupation, as well as work-related characteristics, must be examined in assessing this relationship. In this study, the relationship of work and contextual characteristics-assessed at midpregnancy and including scores on an occupational fatigue index-to preterm delivery was examined among 943 black and 425 white low-income multiparous women who were at risk for a poor pregnancy outcome. At 24 to 26 weeks gestational age, a 77-item questionnaire was self-administered to obtain derailed information on sociodemographic and contextual characteristics, home physical activities, and occupational characteristics. Questions in the occupational section of the questionnaire included most of those previously used by Mamelle and coworkers in 1984 and 1987 to construct an occupational fatigue index. The overall preterm delivery rate for black women was 14.0 percent and for white women, 9.6 percent. No relationships were observed between age, education, or marital status and preterm delivery, or between work status, hours per week, transportation, travel rime, reliability of child care, or home physical activity and preterm delivery for either black women or white women. Black (but not white) women who continued to work at midpregnancy and who reported being able to take rest breaks when they felt tired had a lower preterm delivery rate (10.4 percent versus 21.9 percent; P = 0.031) compared with those who could or did not. Generally, scores for individual sources and levels of occupational fatigue, as well as total occupational fatigue index scores, were unrelated to preterm delivery in this relatively homogeneous group of low-income high-risk women. C1 UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,BIRMINGHAM,AL. NIDOCD,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD. RP HICKEY, CA (reprint author), UNIV ALABAMA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,112 MORTIMER JORDAN HALL,1825 UNIV BLVD,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811]; PHS HHS [MCJ-9040] NR 37 TC 25 Z9 26 U1 2 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1995 VL 110 IS 4 BP 410 EP 418 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RP416 UT WOS:A1995RP41600009 PM 7638328 ER PT J AU LAMBERT, EY CACES, MF AF LAMBERT, EY CACES, MF TI CORRELATES OF DRUG-ABUSE AMONG HOMELESS AND TRANSIENT PEOPLE IN THE WASHINGTON, DC, METROPOLITAN-AREA IN 1991 SO PUBLIC HEALTH REPORTS LA English DT Article ID MENTAL-DISORDERS; DUAL DIAGNOSIS; HEALTH-STATUS; ALCOHOL; USERS AB Sociodemographic correlates of drug use among the general household population may have less accuracy and utility for describing risk factors for drug use among nonhousehold populations like the homeless and transient. This analysis examines correlates of past year use of marijuana, cocaine, and needles among homeless and transient people in the Washington, DC, metropolitan statistical area (DC MSA) and discusses them vis-a-vis traditional indicators of drug use among the general household population. Data are from a study conducted in the DC MSA in 1991 that used a multistage sampling design and surveyed a random sample of 908 homeless and transient people ages 12 years and older. The analysis uses multiple logistic regression to assess the independent effects of demographic and other predictors on selected drug use measures among this population. Three key socioeconomic correlates of drug use among the general household population (educational attainment, employment status, and marital status) were nonsignificant predictors of drug use among the homeless. However, other factors were significant, including past year institutionalization, location within the DC MSA, and stage of homelessness. The age group at greatest risk for use of marijuana and cocaine in the past year were the homeless ages 26 to 34, but the oldest group (35 years and older) had the highest risk of needle use. Although men were more likely to have used marijuana and cocaine in the past year, there were no sex differences in the use of needles in the past year. Only past year use of cocaine differed significantly by race or ethnicity, with a greater likelihood among homeless blacks than among homeless whites. Measures of social achievement and socioeconomic status related to the prevalence and risks of drug use among the general household population have but limited applicability in predicting drug use among people who are homeless and transient. Along with other indicators of behavioral and health risks, history of institutionalization, urbanization, and chronicity of homelessness should be considered to improve the epidemiologic assessment of this population. C1 CSR INC,WASHINGTON,DC. RP LAMBERT, EY (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,COMMUN RES BRANCH,9A-42 PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 29 TC 15 Z9 15 U1 2 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1995 VL 110 IS 4 BP 455 EP 461 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RP416 UT WOS:A1995RP41600014 PM 7638333 ER PT J AU MILLER, RW AF MILLER, RW TI DARLING,GEORGE,B., DR PH, LLD (HON) - 1905-1995 - IN-MEMORIAM - AN APPRECIATION SO RADIATION RESEARCH LA English DT Item About an Individual RP MILLER, RW (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1995 VL 143 IS 1 BP 111 EP 112 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA RG265 UT WOS:A1995RG26500016 ER PT J AU RON, E PRESTON, DL MABUCHI, K AF RON, E PRESTON, DL MABUCHI, K TI UNTITLED - RESPONSE SO RADIATION RESEARCH LA English DT Letter C1 RADIAT EFFECTS RES FDN,DEPT STAT,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. RP RON, E (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1995 VL 143 IS 1 BP 116 EP 117 DI 10.2307/3578938 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA RG265 UT WOS:A1995RG26500020 PM 7639847 ER PT J AU WANG, CY LE, SY ALI, N SIDDIQUI, A AF WANG, CY LE, SY ALI, N SIDDIQUI, A TI AN RNA PSEUDOKNOT IS AN ESSENTIAL STRUCTURAL ELEMENT OF THE INTERNAL RIBOSOME ENTRY SITE LOCATED WITHIN THE HEPATITIS-C VIRUS 5'-NONCODING REGION SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE HEPATITIS C VIRUS; INTERNAL INITIATION OF TRANSLATION; INTERNAL RIBOSOME ENTRY SITE; PSEUDOKNOT ID NON-B-HEPATITIS; MESSENGER-RNA; NON-A; SECONDARY STRUCTURE; PICORNAVIRUS RNA; POLIOVIRUS RNA; TRANSLATION; INITIATION; SEQUENCE; GENOME AB Translation of the human hepatitis C virus (HCV) RNA genome occurs by a mechanism known as ''internal ribosome entry.'' This unusual strategy of translation is employed by naturally uncapped picornaviral genomic RNAs and several cellular mRNAs. A common feature of these RNAs is a relatively long 5' noncoding region (NCR) that folds into a complex secondary structure harboring an internal ribosome entry site (IRES). Evidence derived from the use of dicistronic expression systems, combined with an extensive mutational analysis, demonstrated the presence of an IRES within the HCV 5'NCR. The results of our continued mutational analysis to map the critical structural elements of the HCV IRES has led to the identification of a pseudoknot structure upstream of the initiator AUG. The evidence presented in this study is based upon the mutational analysis of the putative pseudoknot structure. This is further substantiated by biochemical and enzymatic probing of the wild-type and mutant 5'NCR. Further, the thermodynamic calculations, based upon a modified RNAKNOT program, are consistent with the presence of a pseudoknot structure located upstream of the initiator AUG. Maintenance of this structural element is critical for internal initiation of translation. The pseudoknot structure in the 5'NCR represents a highly conserved feature of all HCV subtypes and members of the pestivirus family, including hog cholera virus and bovine viral diarrhea virus. C1 UNIV COLORADO,HLTH SCI CTR,DEPT MICROBIOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,PROGRAM MOLEC BIOL,DENVER,CO 80262. NCI,MATH BIOL LAB,FREDERICK,MD 21701. FU NIDDK NIH HHS [5 P30 DK34914] NR 53 TC 194 Z9 195 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUL PY 1995 VL 1 IS 5 BP 526 EP 537 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX513 UT WOS:A1995RX51300009 PM 7489514 ER PT J AU FOLEY, DJ MONJAN, AA BROWN, SL SIMONSICK, EM WALLACE, RB BLAZER, DG AF FOLEY, DJ MONJAN, AA BROWN, SL SIMONSICK, EM WALLACE, RB BLAZER, DG TI SLEEP COMPLAINTS AMONG ELDERLY PERSONS - AN EPIDEMIOLOGIC-STUDY OF 3 COMMUNITIES SO SLEEP LA English DT Article DE SLEEP COMPLAINTS; INSOMNIA; AGING; EPIDEMIOLOGY; MORTALITY ID ESTABLISHED POPULATIONS; SUBJECTIVE INSOMNIA; PREVALENCE; DISORDERS; DISTURBANCES; MORTALITY; HOME; OLD AB The frequencies of five common sleep complaints - trouble falling asleep, waking up, awaking too early, needing to nap and not feeling rested-were assessed in over 9,000 participants aged 65 years and older in the National Institute on Aging's multicentered study entitled ''Established Populations for Epidemiologic Studies of the Elderly'' (EPESE). Less than 20% of the participants in each community rarely or never had any complaints, whereas over half reported at least one of these complaints as occurring most of the time. Between 23% and 34% had symptoms of insomnia, and between 7% and 15% percent rarely or never felt rested after waking up in the morning. In multivariate analyses, sleep complaints were associated with an increasing number of respiratory symptoms, physical disabilities, nonprescription medications, depressive symptoms and poorer self-perceived health. Sleep disturbances, particularly among older persons, oftentimes may be secondary to coexisting diseases. Determining the prevalence of specific sleep disorders, independent of health status, will require the development of more sophisticated and objective measures of sleep disturbances. C1 NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. DUKE UNIV,DEPT PSYCHIAT,DURHAM,NC 27706. RP FOLEY, DJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,ROOM 3C-309 BETHESDA GATEWAY BLDG,7201 WISCONSIN,BETHESDA,MD 20892, USA. NR 42 TC 723 Z9 738 U1 7 U2 34 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD JUL PY 1995 VL 18 IS 6 BP 425 EP 432 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RK974 UT WOS:A1995RK97400004 PM 7481413 ER PT J AU LEYENDECKER, B LAMB, ME SCHOLMERICH, A FRACASSO, MP AF LEYENDECKER, B LAMB, ME SCHOLMERICH, A FRACASSO, MP TI THE SOCIAL WORLDS OF 8-MONTH-OLD AND 12-MONTH-OLD INFANTS - EARLY EXPERIENCES IN 2 SUBCULTURAL CONTEXTS SO SOCIAL DEVELOPMENT LA English DT Article DE CROSS-CULTURAL COMPARISON; CHILD REARING PRACTICES; SOCIAL VALUES; INFANT EXPERIENCE ID INDIVIDUALISM; PERSPECTIVES; PSYCHOLOGY; CHILDREN AB In this study, we explored the everyday experiences of 40 infants from families who migrated recently from Central America to the US. Another 42 infants from middle class families of Euro-American background were included to facilitate the evaluation of our methodology and findings. Detailed descriptions of the previous 24 hours were obtained by interviewing the mothers when their infants were 8 and 12 months of age. The infants' experiences and activities were very similar in both groups, and the effects of the mothers', fathers' or others' presence on ongoing activities were similar, too. The groups differed with regard to (1) the circadian distribution of activities, (2) opportunities for interactions with various people, and (3) the differences between weekdays and weekends. Overall, the social worlds of the Central American children were characterized by the simultaneous presence of several people and thus by multiple social partners. The social worlds of the Euro-American children were characterized by more opportunities for dyadic interactions and by exposure to fewer partners. RP LEYENDECKER, B (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 45 TC 11 Z9 13 U1 0 U2 1 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0961-205X J9 SOC DEV JI Soc. Dev. PD JUL PY 1995 VL 4 IS 2 BP 194 EP 208 DI 10.1111/j.1467-9507.1995.tb00060.x PG 15 WC Psychology, Developmental SC Psychology GA RL845 UT WOS:A1995RL84500006 ER PT J AU POTTER, LB ROGLER, LH MOSCICKI, EK AF POTTER, LB ROGLER, LH MOSCICKI, EK TI DEPRESSION AMONG PUERTO-RICANS IN NEW-YORK-CITY - THE HISPANIC HEALTH AND NUTRITION EXAMINATION SURVEY SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; UNITED-STATES; PSYCHIATRIC-DISORDERS; COMMUNITY SAMPLE; SYMPTOMS; PREVALENCE; VALIDITY; ACCULTURATION; RELIABILITY; AMERICANS AB This study was conducted to analyze determinants of depression among Puerto Ricans by replicating and expanding earlier studies of depression among Cuban Americans and Mexican Americans. Data from the Hispanic Health and Nutrition Examination Survey, 1982-1984, were employed to examine depression and associated characteristics among Puerto Ricans. We utilized descriptive and multivariate statistics to examine the Center for Epidemiologic Studies Depression Scale (CES-D)-assessed depressive symptomatology and the DSM-III/DIS specification of major depression. The findings indicated that CES-D-assessed depressive symptomatology among Puerto Ricans was associated with female gender, disrupted marital status, poor health, and lower socioeconomic status as indicated by low education, low household income, age, and unemployment. For both 6-month and 1-month DIS major depression, age, disrupted marital status, and income of less than $ 5,000 were significant risk factors. For 6-month DIS major depression, never-married persons had a higher risk for depression. For 1-month diagnoses, writing Spanish better than English was associated with lower risk. In general, our findings for Puerto Ricans were similar to studies of depression among other Hispanic groups. We remained unable to explain the relatively extreme levels of depression among Puerto Ricans in New York, though several probable explanations are elaborated. We emphasized the general need to expand the range of research designs and current risk models in epidemiology in an effort to capture the complexity of psychosocial and cultural processes relevant to psychological distress. C1 FORDHAM UNIV,HISPAN RES CTR,BRONX,NY 10458. NATL INST MENTAL HLTH,PREVENT RES BRANCH,ROCKVILLE,MD. RP POTTER, LB (reprint author), CTR DIS CONTROL,CTR PREVENT SERV,ATLANTA,GA 30333, USA. FU NCRR NIH HHS [SO7 RRO7150-17]; NIMH NIH HHS [2RO1 MH30569] NR 36 TC 46 Z9 47 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUL PY 1995 VL 30 IS 4 BP 185 EP 193 DI 10.1007/BF00790657 PG 9 WC Psychiatry SC Psychiatry GA RJ202 UT WOS:A1995RJ20200006 PM 7491514 ER PT J AU WANG, LM KEEGAN, A FRANKEL, M PAUL, WE PIERCE, JH AF WANG, LM KEEGAN, A FRANKEL, M PAUL, WE PIERCE, JH TI SIGNAL-TRANSDUCTION THROUGH THE IL-4 AND INSULIN-RECEPTOR FAMILIES SO STEM CELLS LA English DT Review DE IL-4; INSULIN; SIGNAL TRANSDUCTION; IRS-1; 4PS; PHOSPHOTYROSINE ID HUMAN INTERLEUKIN-4 RECEPTOR; PROTEIN-TYROSINE PHOSPHORYLATION; COLONY-STIMULATING FACTOR; T-CELL LINE; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; KINASE-ACTIVITY; INTACT-CELLS; FACTOR-I; EXPRESSION AB Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation, Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin, A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily, Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines, Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Pes tyrosine kinases. Unlike several other hematopoietins, IL-4 stimulation has been shown to mediate tyrosine phosphorylation of the substrates, IRS-1 and 4PS. In this review, the signal transduction cascade evoked by IL-4 will be analyzed and compared with those utilized by other cytokines as well as by insulin and IGF-1, The role of 4PS/IRS-1 expression in mediating mitogenesis by IL-4, insulin and IGF-I will also be discussed, C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIH,NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 47 TC 15 Z9 15 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 1995 VL 13 IS 4 BP 360 EP 368 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA RG420 UT WOS:A1995RG42000006 PM 7549895 ER PT J AU SHEARER, GM AF SHEARER, GM TI RESISTING AIDS - ANOTHER VACCINE APPROACH SO TECHNOLOGY REVIEW LA English DT Article C1 UNIV MILAN,DEPT IMMUNOL,MILAN,ITALY. RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,CELL MEDIATED IMMUN SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS INST TECHNOL PI CAMBRIDGE PA CAMBRIDGE, MA 02139 SN 0040-1692 J9 TECHNOL REV JI Technol. Rev. PD JUL PY 1995 VL 98 IS 5 BP 23 EP 27 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RC274 UT WOS:A1995RC27400015 ER PT J AU GUEYFFIER, F BOUTITIE, F BOISSEL, JP COOPE, J CUTLER, J EKBOM, T FAGARD, R FRIEDMAN, L PERRY, HM POCOCK, S PRINEAS, R SCHRON, E AF GUEYFFIER, F BOUTITIE, F BOISSEL, JP COOPE, J CUTLER, J EKBOM, T FAGARD, R FRIEDMAN, L PERRY, HM POCOCK, S PRINEAS, R SCHRON, E TI INDANA - A METAANALYSIS ON INDIVIDUAL PATIENT DATA IN HYPERTENSION - PROTOCOL AND PRELIMINARY-RESULTS SO THERAPIE LA English DT Article DE HYPERTENSION; DRUG TREATMENT; METAANALYSIS BASED ON INDIVIDUAL PATIENT DATA; RESPONDER; PRIMARY PREVENTION; RANDOMIZED CONTROLLED TRIALS ID BLOOD-PRESSURE; MILD HYPERTENSION; DRUG-TREATMENT; TRIAL; MORBIDITY; MORTALITY; DISEASE; HEALTH AB The overall effect of antihypertensive drug treatment has been well documented The proportion of patients who benefit varies according to their baseline cardiovascular risk, and is small for the majority of people treated. Some investigators propose limiting the treatment target population to patients at high cardiovascular risk, but several assumptions must be made to justify this procedure. The INDANA project is a meta-analysis based on individual patient data, and thus offers the opportunity to check the validity of these assumptions. Its main objective is to identify responders (and non-responders) in the drug treatment of hypertension. The rationale and methods for such an approach are presented here, with the solution for some technical problems. The conclusion of the data collection has shown that the project is feasible. The results of the main analysis should be available in 1996, and should contribute to the selection of responders and to the individualization of the treatment of hypertension. C1 NHLBI,BETHESDA,MD 20892. LUND UNIV,DEPT COMMUNITY HLTH SCI,LUND,SWEDEN. CATHOLIC UNIV LEUVEN,DEPT PATHOPHYSIOL,HYPERTENS & CARDIOVASC REHABIL UNIT,B-3000 LOUVAIN,BELGIUM. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. UNIV MIAMI,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,MIAMI,FL. RP GUEYFFIER, F (reprint author), SERV PHARMACOL CLIN,LYON,FRANCE. RI Gueyffier, Francois/B-8545-2008 OI Gueyffier, Francois/0000-0002-9921-0977 NR 44 TC 58 Z9 60 U1 0 U2 1 PU JOHN LIBBEY & CO LTD PI LONDON PA 13 SMITHS YARD SUMMERLEY ST, LONDON, ENGLAND SW18 4HR SN 0040-5957 J9 THERAPIE JI Therapie PD JUL-AUG PY 1995 VL 50 IS 4 BP 353 EP 362 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RY360 UT WOS:A1995RY36000007 PM 7482389 ER PT J AU BLAZKA, ME WILMER, JL HOLLADAY, SD WILSON, RE LUSTER, MI AF BLAZKA, ME WILMER, JL HOLLADAY, SD WILSON, RE LUSTER, MI TI ROLE OF PROINFLAMMATORY CYTOKINES IN ACETAMINOPHEN HEPATOTOXICITY SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED HEPATIC NECROSIS; IL-1 RECEPTOR ANTAGONIST; CULTURED RAT HEPATOCYTES; ACTIVATED MACROPHAGES; INDUCED HYPOTHERMIA; DRUG-METABOLISM; POTENTIAL ROLE; KUPFFER CELLS; INTERLEUKIN-1 AB Acetaminophen (APAP) intoxication has been shown to activate Kupffer cells. Kupffer cell activation is also associated with the release of proinflammatory cytokines which can induce a variety of pathophysiological responses. These studies examined whether proinflammatory cytokines are produced in response to a hepatotoxic dose of APAP, and if so, the role they play in the observed pathological response. Female B6C3F1 mice received 500 mg APAP/kg in the presence and absence of antibodies against tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1 alpha), and IL-1 receptor antagonist (IL-1ra). Serum TNF-alpha, IL-1 alpha, and liver-associated enzyme levels were measured. In addition, the levels of mRNA transcripts for IL-1 alpha, IL-6, and TNF-alpha from livers of treated mice were examined by reverse transcription-polymerase chain reaction (RT-PCR). Administration of APAP resulted in an immediate reduction in body temperature as well as elevated serum levels of IL-1 alpha and TNF-alpha that reached a peak at 12 and 16 hr, respectively. The reduction in body temperature was partially blocked by injection of antibodies against TNF-alpha: or IL-1 alpha. Furthermore, neutralization of TNF-alpha delayed the increase in serum IL-1 alpha and liver enzyme levels. In contrast, pretreatment with IL-1ra antisera exacerbated the effect of APAP on body temperature and increased the release of liver enzymes. These data suggest that TNF-alpha and IL-1 alpha are released in response to APAP intoxication and are responsible for certain pathological manifestations of APAP-induced hepatotoxicity. (C) 1995 Academic Press, Inc. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. VIRGINIA MARYLAND REG COLL VET MED,DEPT BIOMED SCI,BLACKSBURG,VA 24061. NR 47 TC 206 Z9 215 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1995 VL 133 IS 1 BP 43 EP 52 DI 10.1006/taap.1995.1125 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RH954 UT WOS:A1995RH95400006 PM 7597709 ER PT J AU BUSCH, MP ALTER, HJ AF BUSCH, MP ALTER, HJ TI WILL HUMAN-IMMUNODEFICIENCY-VIRUS P24 ANTIGEN SCREENING INCREASE THE SAFETY OF THE BLOOD-SUPPLY AND, IF SO, AT WHAT COST SO TRANSFUSION LA English DT Editorial Material ID DONORS; INFECTION; ANTIBODY; TYPE-1; HIV-1; TRANSMISSION C1 IRWIN MEM BLOOD CTR,SCI SERV,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,INFECT DIS SECT,BETHESDA,MD 20892. RP BUSCH, MP (reprint author), IRWIN MEM BLOOD CTR,RES SERV,SAN FRANCISCO,CA, USA. NR 26 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1995 VL 35 IS 7 BP 536 EP 539 DI 10.1046/j.1537-2995.1995.35795357872.x PG 4 WC Hematology SC Hematology GA RJ261 UT WOS:A1995RJ26100001 PM 7631382 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - PURIFICATION OF HIS-TAG FUSION PROTEINS FROM ESCHERICHIA-COLI SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID METAL CHELATE ADSORBENT AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses a contaminating protein from Escherichia coli found when histidine-tagged fusion proteins are purified by metal chelate affinity chromatography. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 7 TC 70 Z9 71 U1 4 U2 48 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1995 VL 20 IS 7 BP 285 EP 286 DI 10.1016/S0968-0004(00)89045-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RK160 UT WOS:A1995RK16000009 PM 7667882 ER PT J AU KING, KL SQUIER, MKT SELLINS, KS AF KING, KL SQUIER, MKT SELLINS, KS TI CELL-DEATH COMES TO LIFE IN PURGATORY - A KEYSTONE MEETING ON APOPTOSIS SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material C1 UNIV COLORADO,SCH MED,DEPT IMMUNOL,DENVER,CO 80262. RP KING, KL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUL PY 1995 VL 5 IS 7 BP 287 EP 289 DI 10.1016/S0962-8924(00)89041-8 PG 3 WC Cell Biology SC Cell Biology GA RE887 UT WOS:A1995RE88700008 PM 14732114 ER PT J AU CIATTO, S BONARDI, R MAZZOTTA, A LOMBARDI, C SANTONI, R CARDINI, S ZAPPA, M AF CIATTO, S BONARDI, R MAZZOTTA, A LOMBARDI, C SANTONI, R CARDINI, S ZAPPA, M TI COMPARING 2 MODALITIES OF SCREENING FOR PROSTATE-CANCER - DIGITAL RECTAL EXAMINATION PLUS TRANSRECTAL ULTRASONOGRAPHY VS PROSTATE-SPECIFIC ANTIGEN SO TUMORI LA English DT Article DE DIAGNOSIS; PROSTATIC CARCINOMA; SCREENING ID ANTIGEN; CARCINOMA; DIAGNOSIS AB Aims and background: To evaluate the performance and feasibility of screening for prostate cancer by comparing screening modalities. Methods: Prospective study of two comparable cohorts of healthy resident males aged 60 to 75 years. Screening attenders in the two invited cohorts were screened either by digital rectal examination (DRE) and transrectal ultrasonography (TRUS), or by serum prostate-specific antigen determination (PSA: cutoff 4 ng/ml). Attendance and biopsy rates, predictive values, prevalence of screen-detected cancers, as well as screening costs were determined, and the efficiency of the two screening modalities was compared. Results: 1425 subjects were screened by DRE + TRUS. Attendance rate was 33.7%, the biopsy rate was 2.7%, and the prevalence of detected cancers was 1.82%. A total of 1315 subjects was screened by PSA. Attendance rate was 66.9%, the biopsy rate was 2.8%, and the prevalence of detected cancers was 1.67%. Screen-detected cancer stage was more favorable than observed in clinical practice, and early detection was evident, with the prevalence/incidence ratio higher than 10:1 in both programs. The cost per subject screened was about 34,000 Lire for DRE + TRSU and about 30,000 Lire for PSA program. Conclusions: The study confirms that early detection of prostate cancer is possible and that screening is practically feasible. Both screening modalities achieved comparable results as regards early detection, but screening by PSA had a higher compliance and lower costs. PSA seems the ideal test to be used in prospective controlled studies aimed at demonstrating screening efficacy. C1 NATL CANC INST,GENOA,ITALY. TORRE GALLI HOSP,DEPT UROL,FLORENCE,ITALY. SM ANNUNZIATA HOSP,CENT LAB,FLORENCE,ITALY. SM ANNUNZIATA HOSP,DEPT SURG,FLORENCE,ITALY. RP CIATTO, S (reprint author), CTR STUDIO & PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. NR 29 TC 17 Z9 17 U1 0 U2 2 PU CASA EDITRICE AMBROSIANA PI MILAN PA VIA G FRUA 6, 20146 MILAN, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD JUL-AUG PY 1995 VL 81 IS 4 BP 225 EP 229 PG 5 WC Oncology SC Oncology GA TA499 UT WOS:A1995TA49900001 PM 8540115 ER PT J AU LEAPMAN, RD SUN, SQ AF LEAPMAN, RD SUN, SQ TI CRYOELECTRON ENERGY-LOSS SPECTROSCOPY - OBSERVATIONS ON VITRIFIED HYDRATED SPECIMENS AND RADIATION-DAMAGE SO ULTRAMICROSCOPY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Electron Energy Loss Spectroscopy and Imaging (EELSI) CY JUL 24-28, 1994 CL LEUKERBAD, SWITZERLAND SP ATAN, ZEISS, Ecole Polytech Fed Lausanne, Ctr Interdept Microscopie Electr ID BIOLOGICAL SPECIMENS; MICROSCOPY; SPECTRA; WATER; ICE AB Valence electron energy loss spectroscopy (EELS) has been used to characterize the composition of frozen-hydrated specimens in the electron microscope. Fine structure in the energy range up to 30 eV provides a means of distinguishing between vitreous and crystalline ice. Some features of the ice spectrum can be understood in terms of transitions between molecular orbitals in the water molecule and by the existence of excitons in the solid. Spectra from hydrated biological specimens can be analyzed to obtain quantitative estimates of the water content by fitting contributions from the ice and organic components. EELS also provides information about the radiation chemistry that occurs when hydrated specimens are exposed to the electron beam. From the observation of the hydrogen K-edge at similar to 13 eV, it can be deduced that bubbles of molecular hydrogen are evolved during irradiation at doses of > 10(4) nm(-2), and that these bubbles contain gas at pressures in excess of one thousand atmospheres. RP LEAPMAN, RD (reprint author), NATL INST HLTH, NCRR, BIOMED ENGN & INSTRUMENTAT PROGRAM, BLDG 13, ROOM 3N17, BETHESDA, MD 20892 USA. NR 30 TC 69 Z9 69 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 EI 1879-2723 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD JUL PY 1995 VL 59 IS 1-4 BP 71 EP 79 DI 10.1016/0304-3991(95)00019-W PG 9 WC Microscopy SC Microscopy GA RW033 UT WOS:A1995RW03300007 PM 7571121 ER PT J AU SMITH, MR LIU, YL RHEE, SG KUNG, HF AF SMITH, MR LIU, YL RHEE, SG KUNG, HF TI PHOSPHOLIPASE-C SIGNALING SO ZOOLOGICAL STUDIES LA English DT Review DE PHOSPHOLIPASE C SIGNAL TRANSDUCTION ID BOVINE BRAIN; MONOCLONAL-ANTIBODIES; COMPLETE CDNA; SH2 DOMAIN; SEQUENCE; GROWTH; BINDING; PROTEIN; SRC; PHOSPHORYLATION AB Recent experimental evidence indicate that phospholipids also play critical roles as mediators in cell activation and signal transduction. Phospholipases are the key enzymes that regulate Various signalling pathways. Inositol phospholipid-specific phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), to generate inositol triphosphate (IP3) and diacylglycerol (DAG) in response to several receptor-binding growth/differentiation factors, hormones, and neurotransmitters. The hydrolysis products serve as intracellular second messenger molecules which amplify the initial signalling events leading to cellular calcium mobilization by IP3 and protein kinase C (PKC) activation by DAG. In this article, we address two aspects to PLC signalling: 1. characterization, purification and molecular cloning of PLC isozymes; and 2. mitogenic and catalytic activities of PLC isozymes. In addition to reviewing published data on PLC signalling, we have included new data that examine the mitogenic activity of the PLC isozymes. PLC-beta and PLC-gamma induce DNA synthesis after microinjection into quiescent NIH/3T3 cells, while PLC-delta does not exhibit this activity. Monoclonal antibodies to PLC-gamma were shown to block serum-stimulated growth of NIH/3T3 cells and several oncogenes transformed NIH/3T3 cells (fes, src, ras and mos), yet Raf transformed cells were not inhibited by antibody injection. Thus, PLC-gamma signalling is required for serum- and (fes, src, ras and mps) oncogene-induced proliferation of fibroblasts. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BRMP,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP INC,FREDERICK,MD 21702. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 29 TC 0 Z9 1 U1 1 U2 1 PU ACAD SINICA INST ZOOLOGY PI TAIWAN 115 PA EDITORIAL OFFICE TAIPEI, TAIWAN 115, REP OF CHINA SN 1021-5506 J9 ZOOL STUD JI Zool. Stud. PD JUL PY 1995 VL 34 IS 3 BP 141 EP 148 PG 8 WC Zoology SC Zoology GA RP867 UT WOS:A1995RP86700001 ER PT J AU COSO, OA CHIARIELLO, M YU, JC TERAMOTO, H CRESPO, P XU, NG MIKI, T GUTKIND, JS AF COSO, OA CHIARIELLO, M YU, JC TERAMOTO, H CRESPO, P XU, NG MIKI, T GUTKIND, JS TI THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY SO CELL LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; SERINE THREONINE KINASE; DBL-ONCOGENE PRODUCT; MOLECULAR-CLONING; ACTIVATING PROTEINS; CELL-PROLIFERATION; PROTO-ONCOGENE; RAS; RHO; PHOSPHORYLATES AB c-Jun amino-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPKs) are closely related; however, they are independently regulated by a variety of environmental stimuli. Although molecules linking growth factor receptors to MAPKs have been recently identified, little is known about pathways controlling JNK activation. Here, we show that in COS-7 cells, activated Rac1 effectively stimulates MAPK but poorly induces JNK activity. In contrast, mutationally activated Rac1. and Cdc42 GTPases potently activate JNK without affecting MAPK, and oncogenic guanine nucleotide exchange factors for these Rho-like proteins selectively stimulate JNK activity. Furthermore, expression of inhibitory molecules for Rho-related GTPases and dominant negative mutants of Rac1 and Cdc42 block JNK activation by oncogenic exchange factors or after induction by inflammatory cytokines and growth factors. Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP COSO, OA (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALING UNIT,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014; Chiariello, Mario/O-3642-2014 OI Crespo, Piero/0000-0003-2825-7783; Chiariello, Mario/0000-0001-8434-5177 NR 52 TC 1477 Z9 1483 U1 6 U2 22 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 30 PY 1995 VL 81 IS 7 BP 1137 EP 1146 DI 10.1016/S0092-8674(05)80018-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RG910 UT WOS:A1995RG91000018 PM 7600581 ER PT J AU DERUSSO, PA PHILPOTT, CC IWAI, K MOSTOWSKI, HS KLAUSNER, RD ROUAULT, TA AF DERUSSO, PA PHILPOTT, CC IWAI, K MOSTOWSKI, HS KLAUSNER, RD ROUAULT, TA TI EXPRESSION OF A CONSTITUTIVE MUTANT OF IRON REGULATORY PROTEIN-1 ABOLISHES IRON HOMEOSTASIS IN MAMMALIAN-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ELEMENT BINDING-PROTEIN; RESPONSIVE ELEMENT; MESSENGER-RNA AB Iron regulatory proteins (IRPs) are iron-sensing proteins that bind to RNA stem-loop sequences known as iron-responsive elements (IREs) when cells are depleted of iron, Although IRPs have been shown to bind to IREs derived from ferritin and transferrin receptor (TfR) mRNAs in vitro, there has not been a direct demonstration of the impact of a recombinant IRP on the expression of endogenous IRE-containing transcripts, In this study, we evaluate the impact of expression of C437S, a mutant of IRP1 that binds IREs regardless of cellular iron status, on the regulation of biosynthesis of ferritin and TfR. Despite being made iron-replete, cells expressing C437S continue to synthesize and express high amounts of TfR, while the synthesis of ferritin is repressed, Thus, a single mutant IRP can prevent the usual homeostatic changes in ferritin and TfR biosynthesis, Cells expressing the mutant protein would therefore be predicted to be unable to defend against iron overload, Preliminary results show that cells treated with iron have diminished cell survival when C437S is expressed, and we have thus created a tissue culture model system for the study of iron toxicity. RP DERUSSO, PA (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [K12-HD00850] NR 14 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 1995 VL 270 IS 26 BP 15451 EP 15454 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG538 UT WOS:A1995RG53800003 PM 7541043 ER PT J AU USDIN, TB GRUBER, C BONNER, TI AF USDIN, TB GRUBER, C BONNER, TI TI IDENTIFICATION AND FUNCTIONAL EXPRESSION OF A RECEPTOR SELECTIVELY RECOGNIZING PARATHYROID-HORMONE, THE PTH2 RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PEPTIDE RECEPTOR; PANCREATIC-ISLETS; CYTOSOLIC CALCIUM; KIDNEY-CELLS; PROTEIN; HYPOTHALAMUS; RESPONSES; SECRETION; CLONING; TISSUES AB We have identified a G-protein-coupled receptor specifically activated by parathyroid hormone, which we refer to as the PTH2 receptor. Parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP, hypercalcemia of malignancy factor) activate a previously identified PTH/PTHrP receptor, which has a widespread tissue distribution. The PTH2 receptor is much more selective in ligand recognition and appears to have a more specific tissue distribution. It is activated by PTH and not by PTHrP and is particularly abundant in the brain and pancreas. RP USDIN, TB (reprint author), NIMH,CELL BIOL LAB,BLDG 36 RM 3A17,36 CONVENT DR MSC 4090,BETHESDA,MD 20892, USA. NR 40 TC 273 Z9 276 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 30 PY 1995 VL 270 IS 26 BP 15455 EP 15458 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG538 UT WOS:A1995RG53800004 PM 7797535 ER PT J AU OTAKA, A MIYOSHI, K KANEKO, M TAMAMURA, H FUJII, N NOMIZU, M BURKE, TR ROLLER, PP AF OTAKA, A MIYOSHI, K KANEKO, M TAMAMURA, H FUJII, N NOMIZU, M BURKE, TR ROLLER, PP TI DEVELOPMENT OF EFFICIENT 2-STEP DEPROTECTION METHODOLOGY FOR DIMETHYL-PROTECTED PHOSPHOAMINO ACID-CONTAINING PEPTIDE RESINS AND ITS APPLICATION TO THE PRACTICAL SYNTHESIS OF PHOSPHOPEPTIDES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; PHOSPHOTYROSINE-CONTAINING PEPTIDES; BENZYL PHOSPHATE-PROTECTION; O-PHOSPHOTYROSINE; PHOSPHORYLATED PEPTIDES; CHEMICAL SYNTHESIS; CLEAVAGE METHODS; PROTEIN; TYROSINE; ANALOGS AB A protocol has been developed for the synthesis of peptides containing O-phosphorylated tyrosines, serines, and/or threonines. The procedure involves incorporation of dimethyl-protected O-phosphorylated amino acid derivatives (1-3) into peptides using standard Boc chemistry and subsequent removal of Me groups using a two-step deprotection method consisting of high-acidic and low-acidic treatments. Optimized deprotection conditions for the protected resins (4-6) were established, which consist of a combination of the first-step reagent (1 M TMSOTf-thioanisole in TFA (100), m-cresol (5), EDT (5), (v/v)) and the second-step reagent (first-step reagent (110) + DMS-TMSOTf(30:20 to 40:10), (v/v)). The two-step deprotection protocol can be conducted in one pot by appropriate modification of the first-step reagent. The second deprotection step proceeds by an S(N)2 mechanism with little tendency to induce side reactions resulting from harsh acid treatment. A 19-residue MAP-kinase peptide 10 possessing not only two phosphoamino acids but also Met and Trp was subjected to this synthetic procedure and was obtained in 24% yield based on the protected resin. The present synthetic method afforded phosphoamino acid-containing peptides in high yield without significant accompanying side reactions (e.g., loss of phosphate groups, migration of phosphate groups, or alkylation of Met and Trp residues). C1 NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, MED CHEM LAB, BETHESDA, MD 20892 USA. RP OTAKA, A (reprint author), KYOTO UNIV, FAC PHARMACEUT SCI, SAKYO KU, KYOTO 60601, JAPAN. RI Burke, Terrence/N-2601-2014 NR 63 TC 25 Z9 26 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 30 PY 1995 VL 60 IS 13 BP 3967 EP 3974 DI 10.1021/jo00118a011 PG 8 WC Chemistry, Organic SC Chemistry GA RK226 UT WOS:A1995RK22600011 ER PT J AU JEONG, LS MARQUEZ, VE AF JEONG, LS MARQUEZ, VE TI FIRST SYNTHESIS OF A DIDEOXYDIFLUORO NUCLEOSIDE WITH A BETA-D-LYXO CONFIGURATION - AN UNPRECEDENTED EFFECT OF THE CIS-FLUORINES ON THE REACTIVITY OF THE AGLYCON SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note ID 2',3'-DIDEOXYNUCLEOSIDE ANALOGS; DIETHYLAMINOSULFUR TRIFLUORIDE; HIV; AGENTS; PSEUDOROTATION; DERIVATIVES; DAST C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NR 30 TC 8 Z9 8 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 30 PY 1995 VL 60 IS 13 BP 4276 EP 4279 DI 10.1021/jo00118a054 PG 4 WC Chemistry, Organic SC Chemistry GA RK226 UT WOS:A1995RK22600054 ER PT J AU COHEN, SM CLYDESDALE, FM WINTER, C GRAHAM, JD WEIL, WB KROGER, M PARIZA, MW CRAWFORD, LM AVERY, D SCHEUPLEIN, RJ WEISBERGER, E AF COHEN, SM CLYDESDALE, FM WINTER, C GRAHAM, JD WEIL, WB KROGER, M PARIZA, MW CRAWFORD, LM AVERY, D SCHEUPLEIN, RJ WEISBERGER, E TI DELANEY REFORM SO SCIENCE LA English DT Letter C1 UNIV MASSACHUSETTS,AMHERST,MA 01003. UNIV CALIF DAVIS,COOPERAT EXTENS SERV,DAVIS,CA 95616. HARVARD UNIV,SCH PUBL HLTH,CTR RISK ANAL,BOSTON,MA 02115. MICHIGAN STATE UNIV,E LANSING,MI 48823. PENN STATE UNIV,UNIVERSITY PK,PA 16802. UNIV WISCONSIN,MADISON,WI 53706. ASSOC AMER VET MED COLL,WASHINGTON,DC 20005. HUDSON INST,CHURCHVILLE,VA 24421. US FDA,ROCKVILLE,MD 20857. NCI,BETHESDA,MD 20892. RP COHEN, SM (reprint author), UNIV NEBRASKA,MED CTR,OMAHA,NE 68198, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1829 EP 1830 DI 10.1126/science.268.5219.1829-a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000003 PM 7604249 ER PT J AU BLACK, S AF BLACK, S TI PREBIOTIC 5-SUBSTITUTED URACILS AND A PRIMITIVE GENETIC-CODE SO SCIENCE LA English DT Letter ID ORIGIN RP BLACK, S (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1832 EP 1832 DI 10.1126/science.7677859 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000006 PM 7677859 ER PT J AU DENT, P JELINEK, T MORRISON, DK WEBER, MJ STURGILL, TW AF DENT, P JELINEK, T MORRISON, DK WEBER, MJ STURGILL, TW TI REVERSAL OF RAF-1 ACTIVATION BY PURIFIED AND MEMBRANE-ASSOCIATED PROTEIN PHOSPHATASES SO SCIENCE LA English DT Article ID KINASE-ACTIVITY; PHOSPHORYLATION; CELLS; MECHANISM AB The Raf-1 protein kinase participates in transduction of mitogenic signals, but its mechanisms of activation are incompletely understood. Treatment of human Raf-1 purified from insect Sf9 cells co-expressing c-H-Ras and Src(Y527F) (in which phenylalanine replaces tyrosine at residue 527) with either serine-threonine or tyrosine phosphatases resulted in enzymatic inactivation of Raf-1. Inactivation of purified Raf-1 was blocked by addition of either the 14-3-3 zeta protein or heat shock protein 90, Loading of plasma membranes from transformed cells with guanosine triphosphate (GTP) resulted in inactivation of endogenous or exogenous Raf-1; inactivation was blocked by inclusion of protein phosphatase inhibitors. These results suggest the existence of protein phosphatases in the cell membrane that are regulated by GTP and are responsible for Raf-1 inactivation. C1 UNIV VIRGINIA,HOWARD HUGHES MED INST,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,MARKEY CTR CELL SIGNALING,DEPT MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,MARKEY CTR CELL SIGNALING,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS INC,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000]; NIDDK NIH HHS [DK41077]; NIGMS NIH HHS [GM47322] NR 39 TC 179 Z9 180 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1902 EP 1906 DI 10.1126/science.7604263 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000039 PM 7604263 ER PT J AU ZUNIGAPFLUCKER, JC JIANG, D LENARDO, MJ AF ZUNIGAPFLUCKER, JC JIANG, D LENARDO, MJ TI REQUIREMENT FOR TNF-ALPHA AND IL-1-ALPHA IN FETAL THYMOCYTE COMMITMENT AND DIFFERENTIATION SO SCIENCE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TUMOR-NECROSIS-FACTOR; POLYMERASE CHAIN-REACTION; CYTOKINE GENE-EXPRESSION; T-CELLS; PRECURSOR CELLS; C-KIT; INTERLEUKIN-2 RECEPTORS; IMMATURE THYMOCYTES; THYMUS DEVELOPMENT AB CD25 expression occurs early in thymocyte differentiation. The mechanism of induction of CD25 before T cell receptor rearrangement and the importance of this mechanism for T cell development are unknown. In a thymus reconstitution assay, tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha), two cytokines produced within the thymic microenvironment, induced CD25 expression on early immature thymocytes. Either TNF-alpha or IL-1 alpha was necessary for further thymocyte maturation and CD4(+)CD8(+) differentiation. In irradiated mice reconstituted with CD117(+)CD25(+) thymocytes, commitment to the T cell lineage was marked by the loss of precursor multipotency. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 45 TC 117 Z9 119 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1906 EP 1909 DI 10.1126/science.7541554 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000040 PM 7541554 ER PT J AU GALLO, RC AF GALLO, RC TI A SURPRISING ADVANCE IN THE TREATMENT OF VIRAL LEUKEMIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID T-CELL LEUKEMIA; LYMPHOMA; PATIENT RP GALLO, RC (reprint author), NCI,BETHESDA,MD 20892, USA. NR 14 TC 10 Z9 10 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 JUN 29 PY 1995 VL 332 IS 26 BP 1783 EP 1785 DI 10.1056/NEJM199506293322611 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RE667 UT WOS:A1995RE66700011 PM 7760898 ER PT J AU IRIBARREN, C REED, DM BURCHFIEL, CM DWYER, JH AF IRIBARREN, C REED, DM BURCHFIEL, CM DWYER, JH TI SERUM TOTAL CHOLESTEROL AND MORTALITY - CONFOUNDING FACTORS AND RISK MODIFICATION IN JAPANESE-AMERICAN MEN SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; MIDDLE-AGED MEN; FACTOR INTERVENTION TRIAL; CANCER MORTALITY; FOLLOW-UP; CARDIOVASCULAR-DISEASE; INVERSE RELATIONSHIP; PLASMA-CHOLESTEROL; HEMOSTATIC FACTORS; VITAMIN-E AB Objective.-To further investigate the relationship between serum total cholesterol CTG) level and mortality due to major causes. in particular, is the elevated mortality among persons with low TC levels due to confounding conditions that both lower TC level and increase the risk of mortality, and is the association between low or high TC level and mortality homogeneous in the population or, alternatively, restricted to persons with other risk factors? Study Design.-Prospective cohort study. Setting.-Free-living population in Oahu, Hawaii. Participants.-A total of 7049 middle-aged men of Japanese ancestry. Main Outcome Measures.-Age- and risk factor-adjusted mortality due to coronary heart disease, hemorrhagic stroke, cancer, chronic obstructive pulmonary disease, nonmalignant liver disease, trauma, miscellaneous and unknown; and all causes. Results.-During 23 years of follow-up, a total of 1954 deaths were documented (38% cancer, 25% cardiovascular, and 37% other). Men with low serum TC levels (<4.66 mmol/L [<180 mg/dL]) were found to have several adverse health characteristics, including a higher prevalence of current smoking, heavy drinking, and certain gastrointestinal conditions. In an age-adjusted model, and in relation to the reference group (4.66 to 6.19 mmol/L [180 to 239 mg/dL]), those in the lowest TC group (<4.66 mmol/L [<180 mg/dL]) were at significantly higher risk of mortality due to hemorrhagic stroke (relative risk [RR], 2.41; 95% confidence interval [Ci], 1.45 to 4.00), cancer (RR, 1.41; 95% CI, 1.17 to 1.69), and all causes (RR, 1.23; 95% Cl, 1.09 to 1.38). Adjustment for confounders in multivariate analysis (and exclusion of cases with prevalent disease at baseline and deaths through year 5) did not explain the risk of fatal hemorrhagic stroke but reduced the excess risk of cancer mortality by 51% (to 1.20 from 1.41) and reduced the excess risk of all-cause mortality by 56% (to 1.10 from 1.32) in the low TC group. In addition, there were clear differences in the patterns of risk when comparing men with and without selected risk factors tie, smoking, alcohol consumption, and untreated hypertension). Conclusions.-We conclude that the excess mortality at low TC levels can be partially explained by confounding with other determinants of death and by preexisting disease at baseline, and TC-mortality associations are not homogeneous in the population. In our study, TC level was not associated with increased cancer or all-cause mortality in the absence of smoking, high alcohol consumption, and untreated hypertension. C1 UNIV SO CALIF,SCH MED,INST HLTH PROMOT & DIS PREVENT RES,DEPT PREVENT MED,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT MED,INST ARTERIOSCLEROSIS RES,LOS ANGELES,CA 90033. BUCK CTR RES AGING,NOVATO,CA. NHLBI,BETHESDA,MD 20892. HONOLULU HAWAII HEART PROGRAM,HONOLULU,HI. FU NHLBI NIH HHS [N01-HC-02901, N01-HV-02901] NR 58 TC 71 Z9 72 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 JUN 28 PY 1995 VL 273 IS 24 BP 1926 EP 1932 DI 10.1001/jama.273.24.1926 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RE354 UT WOS:A1995RE35400028 PM 7783302 ER PT J AU BAER, L JACOBS, DG CUKOR, P OLAUGHLEN, J COYLE, JT MAGRUDER, KM AF BAER, L JACOBS, DG CUKOR, P OLAUGHLEN, J COYLE, JT MAGRUDER, KM TI AUTOMATED TELEPHONE SCREENING SURVEY FOR DEPRESSION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Note AB Objective.-To test the application of fully automated telephone screening using computerized digital voice recordings and touch-tone responses to assess symptoms of depression. Design.-A cross-sectional study of a 2-week-long telephone survey. Setting.-Toll-free telephone calls placed from home, work, or school to a central telephone/computer system at a telecommunications company in the Boston, Mass, area. Participants.-A total of 1812 participants called the system. Of these, 278 were students and faculty at a large midwestern state university, 725 were employees of a large northeastern high-technology firm, and 809 did not identify which site they were calling from. Main Outcome Measures.-The 20-question multiple-choice Zung Depression Scale was used to screen for depressive symptoms, and additional questions gathered demographic and caller satisfaction information. Results.-No technical problems were encountered during the trial. Of 1812 callers, 1597 (88.1%) completed all questions. Of these, 412 callers (25.8%) met criteria for ''moderate or marked'' depression and another 194 (12.1%) met criteria for ''severe or extreme'' depression. The majority of callers scoring positive for depression had received no previous treatment for depression. Of callers who completed the screening questionnaire, 74.6% reported the call to have been al least ''moderately'' helpful. Conclusion.-Readily available low-cost technology provides a fully automated, widely accessible, and confidential method of screening for a common mental illness. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. NATL DEPRESS SCREENING DAY PROJECT,WELLESLEY,MA. NIMH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DURHAM,NC 27710. NR 9 TC 50 Z9 50 U1 1 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 JUN 28 PY 1995 VL 273 IS 24 BP 1943 EP 1944 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RE354 UT WOS:A1995RE35400031 PM 7783305 ER PT J AU REIZENSTEIN, E HALLANDER, HO BLACKWELDER, WC KUHN, I LJUNGMAN, M MOLLBY, R AF REIZENSTEIN, E HALLANDER, HO BLACKWELDER, WC KUHN, I LJUNGMAN, M MOLLBY, R TI COMPARISON OF 5 CALCULATION MODES FOR ANTIBODY ELISA PROCEDURES USING PERTUSSIS SEROLOGY AS A MODEL SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ELISA; PERTUSSIS; REPRODUCIBILITY; SEROLOGY; STANDARDIZATION; UNIT CALCULATION ID LINKED-IMMUNOSORBENT-ASSAY; ENZYME; EFFICACY; VACCINE; TOXIN; TRIAL; SERA AB During a phase III pertussis vaccine trial, serum antibody responses were measured by two enzyme-linked immunosorbent assays (ELISA) for pertussis toxin and filamentous haemagglutinin. These were used both for studies of antibody levels after vaccination and for diagnostic purposes. Since the absorbance values obtained were not directly proportional to the amount of antibody in the samples, ELISA optical densities were transformed to units by calibration to a reference serum. Five different calculation modes were compared. In four of these modes unit calculations were based on the relationship between dose response curves of the serum sample and a reference serum. In addition, traditional endpoint titres were included in the comparison. The calculation mode using reference line units showed the highest reproducibility, with intraassay coefficients of variation (CV) within the same test plate of 4-7% and interassay CVs of 12-14%. The CVs among the other methods ranged from 6 to 31% for intra-assay comparisons and from 12 to 47% for interassay comparisons. Furthermore, the CV values for intra-assay variations were used to calculate standardized differences between 79 pairs of acute and convalescent sera from cases confirmed by culture. These differences were then used to estimate the 'diagnostic sensitivity' for the different calculation modes. The results indicated that use of the reference line units was the most sensitive, whereas use of the end point titers was the least sensitive of these calculation modes. C1 KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN. NIAID,BETHESDA,MD 20892. RP REIZENSTEIN, E (reprint author), SWEDISH INST INFECT DIS CONTROL,DEPT BACTERIOL,S-10521 STOCKHOLM,SWEDEN. FU PHS HHS [N01-A1-0822, N01-A1-15125] NR 22 TC 71 Z9 71 U1 0 U2 3 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 JUN 28 PY 1995 VL 183 IS 2 BP 279 EP 290 DI 10.1016/0022-1759(95)00067-K PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RG104 UT WOS:A1995RG10400009 PM 7602150 ER PT J AU KOZIKOWSKI, AP MA, DW DU, L LEWIN, NE BLUMBERG, PM AF KOZIKOWSKI, AP MA, DW DU, L LEWIN, NE BLUMBERG, PM TI EFFECT OF ALTERATION OF THE HETEROCYCLIC NUCLEUS OF ILV ON ITS ISOFORM SELECTIVITY FOR PKC - PALLADIUM-CATALYZED ROUTE TO BENZOFURAN ANALOGS OF ILV SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN-KINASE-C; TUMOR PROMOTERS; PHORBOL ESTERS; LYNGBYATOXIN-A; CELLS; ALPHA; ACTIVATION; EPSILON; DIACYLGLYCEROL; OVEREXPRESSION AB The discovery of isoform-selective modulators of protein kinase C (PKC) appears worthwhile in further defining the roles of the individual PKC isoforms in cell type-specific processes. In comparison with the phorbol esters, little information is available regarding the isoform selectivity of the teleocidin family. Blumberg has reported recently that 7-n-octylindolactam V exhibits little if any selectivity for the isoforms tested. In order to probe the possibility of developing isotype-selective agents based on the indolactam V (ILV) structure, we sought to explore replacement of the indole nucleus by a benzofuran ring. Herein we describe a novel palladium-catalyzed route to four benzofuran analogues 11a-d of ILV together with details of their isoform selectivity. Of considerable interest is the unexpected finding that this subtle N to O structural change leads to a compound (11b) that is modestly more like 12,13-dibutyrate phorbol and less like n-octyl-ILV in its pattern of activity. Moreover, the effect of introducing an additional stereocenter at C-14 into these benzofurans was explored, and a clear preference for R-stereochemistry at the C-14 center of the teleocidin family was found, thus providing additional verification of previously published structural correlations between the families of PKC activators. Overall, the present findings provide an important new direction in the quest for isoform-selective activators of PKC. C1 MAYO FDN MED EDUC & RES,JACKSONVILLE,FL 32224. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 38 TC 45 Z9 46 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 28 PY 1995 VL 117 IS 25 BP 6666 EP 6672 DI 10.1021/ja00130a003 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA RG540 UT WOS:A1995RG54000003 ER PT J AU POZSGAY, V AF POZSGAY, V TI SYNTHESIS OF A HEXADECASACCHARIDE FRAGMENT OF THE O-POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ARTIFICIAL SALMONELLA VACCINES; CARBOHYDRATE-CHEMISTRY; REPEATING-UNIT; CHAIN-LENGTH; OLIGOSACCHARIDES; TETRASACCHARIDE; ANTIGEN; GLYCOSIDES; LIPOPOLYSACCHARIDE; TRISACCHARIDE AB A synthetic route is described to a hexadecasaccharide fragment of the O-polysaccharide portion of the lipopolysaccharide of Shigella dysenteriae type 1, a Gram-negative human pathogen. The key intermediate was a trichloroacetimidate derivative of the tetrasaccharide Rha alpha 1-->2Gal alpha 1-->3GlcNAc alpha 1-->3Rha alpha 1-->3 (23) which corresponds to a complete repeating unit of this polysaccharide. Important stages involved the stereoselective construction of a GlcNAc alpha 1-->3Rha synthon (7) which was transformed into a glycosyl acceptor (13) that was alpha-galactosylated in a stereocontrolled reaction with a thiogalactoside donor (14). Conversion of the Gal alpha 1-->3GlcNAc alpha 1-->3Rha intermediate 15 into the glycosyl acceptor 17 followed by stereoselective alpha-rhamnosylation afforded the fully protected tetrasaccharide glycoside from which the tetrasaccharide donor 23 was prepared that contains a selectively removable, benzyl protecting group at the site of the chain extension. The donor was first coupled with 1-decanol to give the tetrasaccharide glycoside 24. One-step conversion provided the tetrasaccharide acceptor 25. Subsequent, iterative glycosylations with the donor 23, used in excess, afforded the fully protected octa-, dodeca-, and hexadecasaccharides, conventional deprotection of which led to di- (2), tri- (3), and tetrameric (4) repeating units of the O-polysaccharide of Sh. dysenteriae type 1. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 70 TC 42 Z9 43 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 28 PY 1995 VL 117 IS 25 BP 6673 EP 6681 DI 10.1021/ja00130a004 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA RG540 UT WOS:A1995RG54000004 ER PT J AU IBEANU, GC GOLDSTEIN, JA AF IBEANU, GC GOLDSTEIN, JA TI TRANSCRIPTIONAL REGULATION OF HUMAN CYP2C GENES - FUNCTIONAL COMPARISON OF CYP2C9 AND CYP2C18 PROMOTER REGIONS SO BIOCHEMISTRY LA English DT Article ID LIVER-SPECIFIC GENES; MEPHENYTOIN HYDROXYLATION; CYTOCHROME-P-450; EXPRESSION; SEQUENCE; SUBFAMILY; PROTEINS; TOLBUTAMIDE; SUPERFAMILY; ENZYMES AB The cytochrome P4502C subfamily comprises a group of constitutive microsomal hemoproteins which are expressed primarily in liver. In humans, this subfamily is responsible for metabolism of a variety of therapeutic drugs such as warfarin, mephenytoin, omeprazole, and antiinflammatory drugs. In the present study, we analyzed the promotor activity of the 5'-flanking region of two human CYP2C genes, CYP2C9 and CYP2C18. The ability of the 2.2-kb 5'-flanking region of the CYP2C9 gene to direct expression of a luciferase reporter gene in HepG2 cells was 25 times greater than that of the 1.3-kb 5'-flanking region of CYP2C18. Deletional analysis of CYP2C9 indicated that the minimal promotor was located between the translation start site and nucleotide -155, and an HPF-1 domain consensus sequence was identified in this region. Gel shift analysis demonstrated that nuclear proteins from HepG2 cells had a high binding affinity for a 20-bp oligonucleotide containing the HPF-1 site of CYP2C9. Antiserum to rat HNF-4 supershifted this DNA-protein complex, and an oligonucleotide derived from an HNF-4 motif present in the human apolipoprotein CIII promotor competed for the supershifted complex, Cotransfection with an HNF-4 expression plasmid increased transcriptional activity of the CYP2C9 minimal promotor (similar to 2-fold) in HepG2 cells and elevated activity more substantially in nonhepatic NIH3T3 cells (26-fold) and Cos 1 cells (9-fold). A possible HPF-1 motif was identified 661 to 641 bases upstream of the translational start site of CYP2C18 which differed from the HPF-1 consensus sequence by the substitution of three cytosines for purines at positions 4-6 and one adenine residue at position 15. An oligonucleotide containing the CYP2C18 HPF-1 motif bound nuclear proteins from HepG2 cells only weakly in gel shift assays, but replacement of the three tandem cytosine residues in the HPF-1 site by guanines using site-directed mutagenesis caused the formation of a complex whose mobility was supershifted by anti-HNF4. Similarly, mutation of the three guanines in the CYP2C9 HPF-1 site to cytosines prevented the formation of the specific DNA-protein complex seen with this motif. However, cotransfection with an HNF-4 expression plasmid did not increase transcriptional activity of CYP2C18 promotor constructs containing the original CYP2C18 HPF-1 motif or the mutated motif containing guanine residues in any of the cell lines tested. We conclude that the HPF-1 site is an important cis-acting element directing hepatic expression of the CYP2C9 promoter but does not contribute to the weak transcriptional activity of the 1.3-kb upstream region of CYP2C18. C1 NIEHS,RES TRIANGLE PK,NC 27709. RI Goldstein, Joyce/A-6681-2012 NR 39 TC 59 Z9 60 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 27 PY 1995 VL 34 IS 25 BP 8028 EP 8036 DI 10.1021/bi00025a008 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG196 UT WOS:A1995RG19600008 PM 7794915 ER PT J AU KUSUI, T HELLMICH, MR WANG, LH EVANS, RL BENYA, RV BATTEY, JF JENSEN, RT AF KUSUI, T HELLMICH, MR WANG, LH EVANS, RL BENYA, RV BATTEY, JF JENSEN, RT TI CHARACTERIZATION OF GASTRIN-RELEASING PEPTIDE RECEPTOR EXPRESSED IN SF9 INSECT CELLS BY BACULOVIRUS SO BIOCHEMISTRY LA English DT Article ID SWISS 3T3 CELLS; SITE-DIRECTED MUTAGENESIS; MUSCARINIC CHOLINERGIC RECEPTORS; PANCREATIC ACINAR-CELLS; HIGH-AFFINITY RECEPTORS; BOMBESIN-LIKE PEPTIDES; PROTEIN-KINASE-C; FUNCTIONAL-CHARACTERIZATION; CHOLECYSTOKININ RECEPTORS; LINKED OLIGOSACCHARIDES AB Whereas baculovirus expression systems have been extensively used for high-level expression of steroid receptors and receptors coupled to adenylate cyclase, there are few studies on peptide receptors coupled to phospholipase C (PLC). In the present study we have expressed the murine gastrin-releasing peptide receptor (mGRP-R) in Sf9 cells using a recombinant baculovirus and characterized it structurally and functionally. mGRP-R was detectible 12 h post infection with recombinant baculovirus carrying mGRP-R cDNA and became maximal at 60 h post infection (B-max = 6 pmol/mg protein), which is a 4-60-fold greater density than is found in native tissues. The mGRP-R in Sf9 cells assessed by affinity labeling or immunoblotting was smaller than that in native tissues (M(r) = 51 kD vs 82 kD), and the difference was due to the extent of glycosylation. In Sf9 cells the mGRP-R had at least two of the four potential extracellular glycosylation sites glycosylated, whereas in the native receptor all four were approximately equally glycosylated. In Sf9 cells the glycosylation was entirely biantennary complex, in contrast to the native mGRP-R, where it was entirely tri- and tetraantennary complex N-linked oligosaccharides. Affinity labeling studies revealed a band with an apparent molecular mass about 40 kDa higher than the 51-kDa mGRP-R band. The intensity of this band correlated with the extent of functional G protein coupling, suggesting that it may represent an mGRP-R-G protein complex. In binding studies the affinity of the mGRP-R in Sf9 cells for the agonists bombesin (Bn), GRP, and neuromedin B (NMB) varied differently with infection time: with Bn the affinity decreased 3-fold with longer infection times, wiht GRP it remained unchanged, and with NMB it decreased 10-fold. GPP(NH)p inhibited binding of either [I-125]Tyr(4)Bn or [I-125]GRP at 24 h post infection, but not at 96 h post infection. Agonists activated PLC, increasing both [H-3]IP and [Ca2+](i); however, the efficacy of each agonist decreased with infection time. These results demonstrate that by the use of recombinant baculovirus infected Sf9 cells the PLC-linked receptor mGRP-R can be expressed in amounts significantly greater than those in native tissues. The mGRP-R expressed in these Sf9 cells is incompletely glycosylated and has less complex N-linked oligosaccharide chains, yet it is fully coupled to G proteins and activates phospholipase C, similar to the native receptor, if short infection times are used. The ability of this system to express mGRP-R in increased amounts should be useful for obtaining enough receptor for making antibodies, performing reconstitution studies, and studying GRP-R modulation by agonists, and this system also provides useful insights into the importance of both glycosylation and G protein coupling with various agonists. C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 76 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 27 PY 1995 VL 34 IS 25 BP 8061 EP 8075 DI 10.1021/bi00025a012 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG196 UT WOS:A1995RG19600012 PM 7794919 ER PT J AU NOBUKUNI, Y SMITH, CL HAGER, GL DETERAWADLEIGH, SD AF NOBUKUNI, Y SMITH, CL HAGER, GL DETERAWADLEIGH, SD TI CHARACTERIZATION OF THE HUMAN GLUCOCORTICOID RECEPTOR PROMOTER SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR AP-2; BOX-BINDING-PROTEINS; GEL-ELECTROPHORESIS; MEDIATES INDUCTION; MOLECULAR-CLONING; MAMMALIAN-CELLS; GENE PROMOTER; ELEMENT; DNA; EXPRESSION AB To elucidate the functional elements that are involved in the regulation of the human glucocorticoid receptor (hGR) gene, transient expression, DNase I footprinting, and gel mobility shift analyses were conducted. We found that the hGR promoter region between -700 and +38 bp contained 11 footprinted sites. Deletion df the -374 to -183 bp region, which is highly conserved between human and mouse (93%), induced a 5-24-fold reduction in promoter activity in HeLa, NIH3T3, CV1, and HepG2 cells. Three footprints, FP5, FP6, and FP7, were shown to map to this region. In particular, the FP7 site was found to be within the -374 to -347 bp region. Deletion of this region triggered a significant decline in promoter activity in HeLa and NIH3T3 cells but not in HepG2 cells. AP2 was found to bind FP7. Tn HepG2 cells AP2 elicited transactivation of the hGR promoter activity. Transfection data revealed that the upstream GC box-rich fragment between -700 and, -375 bp induced a 4-7-fold activation of: the heterologous tk promoter in an orientation-independent manner. Our studies demonstrate that several transcription factors are involved in regulating GR expression and that AP2 could function as an important positive regulator of GR promoter activity. C1 NCI,MOLEC VIROL LAB,HORMONE ACT & ONCOGENESIS SECT,BETHESDA,MD 20822. RP NOBUKUNI, Y (reprint author), NIMH,CLIN NEUROGENET BRANCH,GENE MAPPING & EXPRESS UNIT,BLDG 10,ROOM 3N218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 51 TC 65 Z9 66 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 27 PY 1995 VL 34 IS 25 BP 8207 EP 8214 DI 10.1021/bi00025a028 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG196 UT WOS:A1995RG19600028 PM 7794935 ER PT J AU GILES, WH KITTNER, SJ HEBEL, JR LOSONCZY, KG SHERWIN, RW AF GILES, WH KITTNER, SJ HEBEL, JR LOSONCZY, KG SHERWIN, RW TI DETERMINANTS OF BLACK-WHITE DIFFERENCES IN THE RISK OF CEREBRAL INFARCTION - THE NATIONAL-HEALTH AND NUTRITION EXAMINATION SURVEY EPIDEMIOLOGIC FOLLOW-UP-STUDY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID STROKE; DISEASE AB Objective: To determine whether blacks in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study remained at increased risk for cerebral infarction after adjusting for stroke risk factors and sociodemographic factors. Methods: A cohort study involving 8203 whites and 1362 blacks who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. During the 13-year follow-up, 538 and 122 cerebral infarctions occurred in whites and blacks, respectively. Results: The black-white risk for cerebral infarction varied by age (P=.007 for race-age interaction). Compared with whites of the same age, blacks aged 35 to 44 years were at significantly increased risk for cerebral infarction (relative risk, 2.62; 95% confidence interval, 1.23 to 5.57), while older blacks, those older than 64 years, were not at increased risk (relative risk, 1.14; 95% confidence interval, 0.90 to 1.46). The relative risk for cerebral infarction decreased to 2.07 (95% confidence interval, 0.97 to 4.42) in younger blacks and 0.82 (95% confidence interval, 0.29 to 2.33) in older blacks after adjustment for age, sex, education, history of heart disease, diabetes, systolic blood pressure, treatment for hypertension, Quetelet index, and serum hemoglobin and magnesium levels. Conclusions: These results indicate that much of the increased risk for cerebral infarction experienced by blacks can be explained by their higher prevalence of stroke risk factors, especially diabetes, hypertension, and lower educational attainment. Younger blacks, however, may still be at increased risk after adjusting for stroke risk factors. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,STROKE EPIDEMIOL UNIT,BALTIMORE,MD 21201. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. FU NINDS NIH HHS [K08-NS01319] NR 22 TC 85 Z9 86 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD JUN 26 PY 1995 VL 155 IS 12 BP 1319 EP 1324 DI 10.1001/archinte.155.12.1319 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RD854 UT WOS:A1995RD85400011 PM 7778964 ER PT J AU HOFFMAN, PW CHERNAK, JM AF HOFFMAN, PW CHERNAK, JM TI DNA-BINDING AND REGULATORY EFFECTS OF TRANSCRIPTION FACTORS SP1 AND USF AT THE RAT AMYLOID PRECURSOR PROTEIN GENE PROMOTER SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALZHEIMERS-DISEASE; MESSENGER-RNA; EXPRESSION; UPSTREAM; SV40; SEQUENCES; INVITRO; REGION; MOUSE; CELLS AB Two DNA elements which we have termed SAA and GAG have been shown to control expression of the rat amyloid precursor protein (APP) gene, and the region containing the SAA element has been shown to interact with nuclear proteins [Hoffman and Chernak (1994) Biochem. Biophys. Res. Commun. 201, 610-617]. In this report we study DNA sequences and proteins which influence the activity of the SAA element. An oligonucleotide containing the SAA element is specifically bound by nuclear proteins derived from rat PC12 cells, consistently forming four complexes designated C25, C30, C35 and C40 in electrophoretic mobility shift assays (EMSAs). We demonstrate that the C25, C30 and C40 complexes involve the binding of nuclear proteins to an SP1 consensus sequence located within the SAA element and that the C25 complex contains a protein antigenically related to the human SP1 protein. We establish further that the C35 complex requires a USF recognition site located within the SAA element and contains a protein antigenically related to the human upstream stimulatory factor (USF) protein. Using APP promoter/luciferase reporter gene constructs, we demonstrate that both the SP1 and the USF sites can play a role in the transcriptional activity of the SAA element. Finally, we show that complexes similar to the C25, C30 and C35 complexes are formed by rat cortex nuclear extracts and the SAA element in EMSA experiments, suggesting the relevance of our in vitro observations to the in vivo functioning of the rat APP promoter. C1 NIA,CTR GERONTOL RES,CELLULAR & MOLEC BIOL LAB,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 22 TC 50 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1995 VL 23 IS 12 BP 2229 EP 2235 DI 10.1093/nar/23.12.2229 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH552 UT WOS:A1995RH55200019 PM 7610052 ER PT J AU NIELSEN, DA NOVORADOVSKY, A GOLDMAN, D AF NIELSEN, DA NOVORADOVSKY, A GOLDMAN, D TI SSCP PRIMER DESIGN BASED ON SINGLE-STRAND DNA-STRUCTURE PREDICTED BY A DNA FOLDING PROGRAM SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRYPTOPHAN-HYDROXYLASE GENE; SECONDARY STRUCTURE; COMPUTER-SIMULATION; RNA SEQUENCES; POLYMORPHISM; STABILITY AB To predict alterations in single-strand DNA mobility in non-denaturing electrophoretic gels, Zuker's RNA folding program was modified. Energy files utilized by the LRNA RNA folding algorithm were modified to emulate folding of single-strand DNA. Energy files were modified to disallow G . T base pairing. Stacking energies were corrected for DNA thermodynamics. Constraints on loop nucleotide sequences were removed. The LRNA RNA folding algorithm using the DNA fold energy files was applied to predict folding of PCR generated single-strand DNA molecules from polymorphic human ALDH2 and TPH alleles. The DNA-Fold version 1.0 program was used to design primers to create and abolish SSCP mobility shifts. Primers were made that add a 5' tag sequence or alter complementarity to an internal sequence. Differences in DNA secondary structure were assessed by SSCP analysis and compared to single-strand DNA secondary structure predictions. Results demonstrate that alterations in single-strand DNA conformation may be predicted using DNA-Fold 1.0. C1 NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. RP NIELSEN, DA (reprint author), NIAAA,MOLEC GENET & HUMAN NEUROGENET SECT,BETHESDA,MD 20892, USA. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 29 TC 25 Z9 27 U1 0 U2 4 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 JUN 25 PY 1995 VL 23 IS 12 BP 2287 EP 2291 DI 10.1093/nar/23.12.2287 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH552 UT WOS:A1995RH55200026 PM 7610057 ER PT J AU RHODES, C YAMADA, Y AF RHODES, C YAMADA, Y TI CHARACTERIZATION OF A GLUCOCORTICOID-RESPONSIVE ELEMENT AND IDENTIFICATION OF AN AT-RICH ELEMENT THAT REGULATE THE LINK PROTEIN GENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID THYROID-HORMONE RECEPTOR; GROWTH FACTOR-I; CHLORAMPHENICOL ACETYLTRANSFERASE; TRANSCRIPTION FACTOR; HOMEODOMAIN PROTEIN; OSTEO-ARTHRITIS; CHICK-EMBRYO; CARTILAGE; RAT; CHONDROCYTES AB The cartilage matrix is composed of characteristic components including type II collagen, aggrecan and link protein. In this paper, we report two DNA elements that regulate the link protein gene. Using transient transfection assays with link protein gene constructs in chondrocytes, chloramphenicol acetyl transferase (CAT) assays were used to measure the transcriptional activity of the link protein gene. Previously, we identified an enhancer-like activity within the first intron of the gene. In this paper, we report an active 34 bp (+1390 to +1424) fragment within this region that contains a glucocorticoid-like response element (GRE). Both deletion of, and site-specific mutations within this sequence motif reduced the dexamethasone-inducible activity. The GRE-like sequence from the rat link protein gene, or the homologous sequence from the human link protein gene were included in vectors containing the thymidine kinase promoter linked to the CAT gene (tkCAT). Both human and rat elements transferred the ability to respond to dexamethasone and hydrocortisone with a >10-fold induction. Deletions through the promoter from -923 to -900 identified a second site required for both glucocorticoid and serum responsiveness. A four base substitution at this site resulted in a loss of serum responsiveness. This region contains an AT-rich element, similar to the AT-rich elements involved in homeotic protein regulation of the growth hormone gene and the muscle creatine kinase gene. Southwestern analysis using oligonucleotides containing the AT-rich element from the link protein gene or the muscle creatine kinase gene, identified a 32 kDa protein band from nuclear extracts of chick chondrocytes. Using these AT-rich oligonucleotides in band-shift analyses, nuclear extracts of chick sternal muscle, rat chondrosarcoma and chick sternal chondrocytes each showed formation of different complexes suggesting cell specificity. AT-rich elements have been identified as binding sites for homeodomain-containing proteins and can contribute to gene regulation by serum response factors. The identification of an AT-rich element in the link protein gene suggests similar functions for this element. RP RHODES, C (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 59 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1995 VL 23 IS 12 BP 2305 EP 2313 DI 10.1093/nar/23.12.2305 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH552 UT WOS:A1995RH55200029 PM 7610060 ER PT J AU SHIPPENBERG, TS HEIDBREDER, C AF SHIPPENBERG, TS HEIDBREDER, C TI THE DELTA-OPIOID RECEPTOR ANTAGONIST NALTRINDOLE PREVENTS SENSITIZATION TO THE CONDITIONED REWARDING EFFECTS OF COCAINE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE COCAINE; NALTRINDOLE; ENKEPHALIN; DELTA-OPIOID RECEPTOR; COCAINE-INDUCED SENSITIZATION ID MESSENGER-RNA EXPRESSION; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; BRAIN-STIMULATION; MOTOR-ACTIVITY; BEHAVIORAL SENSITIZATION; RAT; INCREASES; AMPHETAMINE AB A conditioned place preference paradigm was used to determine whether: (i) prior exposure to cocaine results in an enhancement of its rewarding effects, and (ii) the delta-opioid receptor antagonist naltrindole can prevent the development of this response. Rats received daily injections of saline or cocaine (10.0 mg/kg i.p.) for 5 days in the colony room. Additional animals received naltrindole (0.03-0.3 mg/kg s.c.), lithium chloride (20 mg/kg s.c.) or vehicle prior to i.p. injections. Conditioning sessions (2 drug; 2 vehicle) commenced 3 days later. Cocaine (1.0-10.0 mg/kg) was ineffective as a conditioning stimulus in saline pre-exposed rats. In cocaine pre-exposed animals, however, doses of 5.0 and 10.0 mg/kg cocaine resulted in significant drug-induced place preferences. Significant cocaine-induced place preferences were also observed in animals which had received lithium chloride with the cocaine treatment regimen. In animals which had received naltrindole together with the chronic cocaine treatment regimen, cocaine failed to produce a conditioned response. These data demonstrate that the repeated administration of cocaine results in an enhancement of its rewarding effects (e.g. sensitization) and that this phenomenon is prevented by a delta-opioid receptor antagonist. Furthermore, the finding that naltrindole does not modify the acute rewarding effects of cocaine suggests a specific role of delta-opioid receptors in the sensitization process. RP SHIPPENBERG, TS (reprint author), NIDA,INTRAMURAL RES PROGRAM,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 48 TC 47 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 23 PY 1995 VL 280 IS 1 BP 55 EP 61 DI 10.1016/0014-2999(95)00185-N PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RF673 UT WOS:A1995RF67300007 PM 7498254 ER PT J AU BROWN, HA GUTOWSKI, S KAHN, RA STERNWEIS, PC AF BROWN, HA GUTOWSKI, S KAHN, RA STERNWEIS, PC TI PARTIAL-PURIFICATION AND CHARACTERIZATION OF ARF-SENSITIVE PHOSPHOLIPASE-D FROM PORCINE BRAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; PROTEIN-KINASE-C; ADENYLATE-CYCLASE; REGULATORY COMPONENT; HYDRODYNAMIC PROPERTIES; CHOLERA-TOXIN; BINDING; HYDROLYSIS; ACTIVATION; CGMP AB Phospholipase D (PLD) activity from membranes of cultured cells can be activated by guanosine 5'-O-(3-thiotriphosphate) and the small GTP-dependent protein, Arf. While this activity was readily apparent in membranes from HL60 cells, it was much lower or not observable in membranes from various mammalian tissues. However, extraction of porcine brain membranes with detergent and subsequent chromatography with SP-Sepharose revealed a large peak of Arf-sensitive PLD activity. This activity has been enriched through several steps of chromatography and characterized with respect to size, nucleotide specificity, and sensitivity to different Arf and Arf-like proteins. Hydrodynamic analysis indicated that the enriched PLD had an s(20,w) of 5.1 and a Stokes radius of 4.3 nm. These parameters indicate that the enzyme has an apparent molecular mass of 95,000 Da. Effective stimulation of the enriched enzyme was achieved with GTP as well as nonhydrolyzable analogs. All of the Arf subtypes tested were effective activators of PLD activity. Arf derived from yeast could activate mammalian PLD but with lower potency. The Arf-related Arl proteins were ineffective. PLD that has been highly enriched retained a requirement for phosphatidylinositol 4,5-bisphosphate for efficient expression of activity. Additionally, the ability of recombinant or purified porcine brain Arf to stimulate PLD activity was reduced relative to impure fractions of Arf activity. Thus, porcine PLD that has been purified about 5,000-10,000-fold is synergistically activated by Arf in combination with other cytosolic components that are described in the accompanying paper (Singer, W. D., Brown, H. A., Bokoch, G. M., and Sternweis, P. C. (1995) J. Biol. Chem. 270, 14944-14950). Taken together, these data suggest that physiological regulation of Arf-sensitive PLD may involve the coordinate assembly of several interacting regulatory subunits. C1 UNIV TEXAS, SW MED CTR, DEPT PHARMACOL, DALLAS, TX 75235 USA. NCI, DIV CANC TREATMENT, BIOL CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM15817, GM31954] NR 45 TC 124 Z9 124 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 23 PY 1995 VL 270 IS 25 BP 14935 EP 14943 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600017 PM 7797473 ER PT J AU MAITRA, RK LI, GY XIAO, W DONG, BH TORRENCE, PF SILVERMAN, RH AF MAITRA, RK LI, GY XIAO, W DONG, BH TORRENCE, PF SILVERMAN, RH TI CATALYTIC CLEAVAGE OF AN RNA TARGET BY 2-5A ANTISENSE AND RNASE-L SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERFERON-TREATED CELLS; DOUBLE-STRANDED-RNA; PROTEIN-SYNTHESIS; PPP(A2'P)NA-DEPENDENT RNASE; CONSTITUTIVE EXPRESSION; 2-5A-DEPENDENT RNASE; JLS-V9R CELLS; INHIBITION; 2',5'-OLIGOADENYLATE; PPPA2'P5'A2'P5'A AB 2-5A antisense (2-5A-AS) molecules are chimeric oligonucleotides that cause 2-5A-dependent RNase (RNase L) to catalyze the selective cleavage of RNA in human cells. These composite nucleic acids consist of a 5'-monophosphorylated, 2',5'-linked oligoadenylate known as 2-5A (an activator of RNase L) covalently attached to antisense 3',5'-oligodeoxyribonucleotides. Here, we characterize the targeted cleavage of the double-stranded RNA-dependent protein kinase (PKR) mRNA by purified, recombinant human RNase L. A 2-5A-AS chimera, which contains complementary sequence to PKR mRNA, and unmodified 2-5A, which causes general RNA decay, were about 20- and 40-fold more active, respectively, than 2-5A-AS chimeras in which the DNA domains are not complementary to sequences in PKR mRNA. Directed cleavage was efficient because each 2-5A-AS chimera targeted many RNA molecules. Moreover, RNase L caused the catalytic cleavage of the RNA target (k(cat) of approximately 7 s(-1)). The precise sites of PKR mRNA cleavage caused by 2-5A-AS were mapped, using a primer extension assay, to phosphodiester bonds adjacent to the 3' terminus of the chimera binding site (5' on the RNA target) as well as within the chimera's oligonucleotide binding site itself. The selectivity of this approach is shown to be provided by the antisense arm of the chimera, which places the RNA target in close proximity to the RNase. C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. NIDDK,BIOMED CHEM SECT,BETHESDA,MD 20892. FU NCI NIH HHS [1 PO1 CA 62220-01A1] NR 28 TC 36 Z9 36 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 JUN 23 PY 1995 VL 270 IS 25 BP 15071 EP 15075 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600036 PM 7797490 ER PT J AU BIFULCO, M PERILLO, B SAJI, M LAEZZA, C TEDESCO, I KOHN, LD ALOJ, SM AF BIFULCO, M PERILLO, B SAJI, M LAEZZA, C TEDESCO, I KOHN, LD ALOJ, SM TI REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE GENE-EXPRESSION IN FRTL-5 CELLS .1. IDENTIFICATION AND CHARACTERIZATION OF A CYCLIC AMP-RESPONSIVE ELEMENT IN THE RAT REDUCTASE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HMG COA REDUCTASE; A REDUCTASE; RECEPTOR PROMOTER; MAMMALIAN-CELLS; THYROID-CELLS; TRANSCRIPTION; THYROTROPIN; BINDING; PROTEIN; INVITRO AB Thyrotropin (TSH) increases 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene transcription in FRTL-5 rat thyroid cells, and the effect of TSH can be mimicked by cAMP. Sequence analysis of the rat reductase promoter has revealed a hitherto unnoticed cAMP-responsive element (CRE)-like octamer. This octamer is located between 53 and 60 nucleotides downstream of the sterol regulatory element 1; its first 6 nucleotides are identical to the consensus somatostatin CRE, and the entire octamer is identical to the fos CRE. A synthetic oligonucleotide containing the HMG-CoA reductase CRE-like octamer (RED CRE) formed protein-DNA complexes with nuclear extracts from FRTL-5 cells, which could be prevented by unlabeled CRE-containing oligonucleotides whose flanking sequences were otherwise nonidentical. The complexes were specifically supershifted by anti-CREE antibodies. FRTL-5 cells transfected with a fusion plasmid carrying the bacterial chloramphenicol acetyl transferase (CAT) under the control of the HMG-CoA reductase promoter displayed CAT activity, which was specifically stimulated by TSH. In contrast, CAT activity in FRTL-5 cells transfected with similar constructs carrying mutations in the reductase CRE was significantly lower and did not increase after TSH challenge. We suggest that the HMG-CoA reductase gene contains a functional CRE, important for TSH regulation of transcription. The data presented provide the molecular basis for a novel regulatory mechanism for HMG-CoA reductase gene expression in rat thyroid cells, which involves the direct effect of cAMP. C1 UNIV NAPLES FEDERICO II,CTR ENDOCRINO & ONCOL SPERIMENTALE,CNR,I-80131 NAPLES,ITALY. UNIV REGGIO CALABRIA,DIPARTIMENTO MED SPERIMENTALE & CLIN,I-88100 CATANZARO,ITALY. NIDDK,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. RI Saji, Motoyasu/E-4007-2011; OI Bifulco, Maurizio/0000-0002-1771-4531 NR 31 TC 25 Z9 25 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 JUN 23 PY 1995 VL 270 IS 25 BP 15231 EP 15236 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600058 PM 7797507 ER PT J AU CAI, H YU, H MCENTEE, K KUNKEL, TA GOODMAN, MF AF CAI, H YU, H MCENTEE, K KUNKEL, TA GOODMAN, MF TI PURIFICATION AND PROPERTIES OF WILD-TYPE AND EXONUCLEASE-DEFICIENT DNA-POLYMERASE-II FROM ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MISPAIR EXTENSION KINETICS; SPONTANEOUS MUTATION; BIOCHEMICAL BASIS; REVERSE-TRANSCRIPTASE; POLB GENE; VIRAL-DNA; BACTERIOPHAGE-T4; FIDELITY; MUTANT; SUBSTITUTION AB Wild-type DNA polymerase II (pol II and an exonuclease-deficient pol II mutant (D155A/E157A) have been overexpressed and purified in high yield from Escherichia coli. Wild-type pol II exhibits a high proofreading 3'-exonuclease to polymerase ratio, similar in magnitude to that observed for bacteriophage T4 DNA polymerase. While copying a 250-nucleotide region of the lacZ alpha gene, the fidelity of wild-type pol II is high, with error rates for single-base substitution and frameshift errors being less than or equal to 10(-6). In contrast, the pol II exonuclease-deficient mutant generated a variety of base substitution and single base frameshift errors, as well as deletions between both perfect and imperfect directly repeated sequences separated by a few to hundreds of nucleotides. Error rates for the pol II exonuclease-deficient mutant were from greater than or equal to 13- to greater than or equal to 240-fold higher than for wild-type pol II, depending on the type of error considered. These data suggest that from 90 to >99% of base substitutions, frameshifts, and large deletions are efficiently proofread by the enzyme. The results of these experiments together with recent in vivo studies suggest an important role for pol II in the fidelity of DNA synthesis in cells. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOL CHEM, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA. NIEHS, GENET MOLEC LAB, RES TRIANGLE PK, NC 27709 USA. RP UNIV SO CALIF, HEDCO MOLEC BIOL LABS, DEPT BIOL SCI, LOS ANGELES, CA 90089 USA. FU NIGMS NIH HHS [GM21422, GM29558, GM42554] NR 44 TC 68 Z9 68 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 23 PY 1995 VL 270 IS 25 BP 15327 EP 15335 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600072 PM 7797520 ER PT J AU SCHUMACHER, C KNUDSEN, BS OHUCHI, T DIFIORE, PP GLASSMAN, RH HANAFUSA, H AF SCHUMACHER, C KNUDSEN, BS OHUCHI, T DIFIORE, PP GLASSMAN, RH HANAFUSA, H TI THE SH3 DOMAIN OF CRK BINDS SPECIFICALLY TO A CONSERVED PROLINE-RICH MOTIF IN EPS15 AND EPS15R SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSINE-CONTAINING PROTEINS; DROSOPHILA-TRITHORAX; ACUTE LEUKEMIAS; CDNA; RECEPTOR; SEQUENCE; PRODUCT; SEARCH; REGION; GENE AB The Crk protein belongs to the family of proteins consisting of mainly Src homology 2 and 3 (SH2 and SH3) domains. These proteins are thought to transduce signals from tyrosine kinases to downstream effecters. In order to understand the specificity and effector function of the SH3 domain of Crk, we screened an expression library for binding proteins. We isolated Eps15, a substrate of the epidermal growth factor receptor (EGFR) tyrosine kinase, and Eps15R, a novel protein with high sequence homology to the carboxyl-terminal domain of Eps15. Antibodies raised against a fragment of the Eps15R gene product immunoprecipitated a protein of 145 kDa, Eps15 and Eps15R bound specifically to the amino-terminal SH3 domain of Crk and coprecipitated equivalently with both c-Crk and v-Crk from cell lysates. The amino acid sequences of Eps15 and Eps15R featured several proline-rich regions as putative binding motifs for SH3 domains. In both Eps15 and Eps15R, we identified one proline-rich motif which accounts for their interaction with the Crk SH3 domain. Each binding motif contains the sequence P-X-L-P-X-K, an amino acid stretch that is highly conserved in all proteins known to interact specifically with the first SH3 domain of Crk. Furthermore, we found that immunoprecipitates of activated EGFR-kinase stably bound in vitro-translated Eps15 only in the presence of in vitro-translated v-Crk. Crk might therefore be involved in Eps15-mediated signal transduction through the EGFR. C1 ROCKEFELLER UNIV,MOLEC ONCOL LAB,NEW YORK,NY 10021. NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV HEMATOL ONCOL,NEW YORK,NY 10021. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NCI NIH HHS [CA09673, CA44356] NR 54 TC 82 Z9 83 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 JUN 23 PY 1995 VL 270 IS 25 BP 15341 EP 15347 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600074 PM 7797522 ER PT J AU BAUMANN, MH ROTHMAN, RB AF BAUMANN, MH ROTHMAN, RB TI REPEATED COCAINE ADMINISTRATION REDUCES 5-HT1A-MEDIATED PROLACTIN SECRETION IN RATS SO NEUROSCIENCE LETTERS LA English DT Article DE COCAINE; SEROTONIN (5-HT); 5-HT1A RECEPTORS; PROLACTIN; SEROTONIN SYNDROME ID 5-HT1A RECEPTOR; SEROTONIN; DOPAMINE; SENSITIZATION; STIMULATION; BRAIN AB The prolactin and behavioral responses elicited by the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-{di-n-propylamino}tetralin) were examined in male rats previously exposed to chronic cocaine (15 mg/kg, i.p., b.i.d., 7 days) or saline. After 42 h of withdrawal, cocaine-treated rats exhibited a reduced prolactin response to 8-OH-DPAT challenge (50 mu g/kg, i.v.). A 5-fold higher dose of 8-OH-DPAT stimulated maximal prolactin secretion that was similar in cocaine- and saline-treated rats. Prior cocaine treatment had no effect on the 5-HT syndrome induced by 8-OH-DPAT. Our data agree with the findings of others and suggest that 5-HT1A receptors mediating neuroendocrine secretion become subsensitive after repeated cocaine administration. RP BAUMANN, MH (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,CLIN PSYCHOPHARMACOL SECT,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 26 TC 20 Z9 20 U1 2 U2 2 PU ELSEVIER SCI PUBL 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 JUN 23 PY 1995 VL 193 IS 1 BP 9 EP 12 DI 10.1016/0304-3940(95)11652-D PG 4 WC Neurosciences SC Neurosciences & Neurology GA RH960 UT WOS:A1995RH96000003 PM 7566671 ER PT J AU VARMUS, H AF VARMUS, H TI AN ACTIVE NATIONAL INSTITUTE OF MENTAL-HEALTH SO SCIENCE LA English DT Letter RP VARMUS, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 23 PY 1995 VL 268 IS 5218 BP 1681 EP 1681 DI 10.1126/science.7792582 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RE668 UT WOS:A1995RE66800002 PM 7792582 ER PT J AU SAVITSKY, K BARSHIRA, A GILAD, S ROTMAN, G ZIV, Y VANAGAITE, L TAGLE, DA SMITH, S UZIEL, T SFEZ, S ASHKENAZI, M PECKER, I FRYDMAN, M HARNIK, R PATANJALI, SR SIMMONS, A CLINES, GA SARTIEL, A GATTI, RA CHESSA, L SANAL, O LAVIN, MF JASPERS, NGJ MALCOLM, A TAYLOR, R ARLETT, CF MIKI, T WEISSMAN, SM LOVETT, M COLLINS, FS SHILOH, Y AF SAVITSKY, K BARSHIRA, A GILAD, S ROTMAN, G ZIV, Y VANAGAITE, L TAGLE, DA SMITH, S UZIEL, T SFEZ, S ASHKENAZI, M PECKER, I FRYDMAN, M HARNIK, R PATANJALI, SR SIMMONS, A CLINES, GA SARTIEL, A GATTI, RA CHESSA, L SANAL, O LAVIN, MF JASPERS, NGJ MALCOLM, A TAYLOR, R ARLETT, CF MIKI, T WEISSMAN, SM LOVETT, M COLLINS, FS SHILOH, Y TI A SINGLE ATAXIA-TELANGIECTASIA GENE WITH A PRODUCT SIMILAR TO PI-3 KINASE SO SCIENCE LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; IONIZING-RADIATION; DNA-SYNTHESIS; COMPLEMENTATION ANALYSIS; CDNA SELECTION; FAMILIES; PROTEIN; CELLS; PATHWAYS; CANCERS AB A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,INST HUMAN GENET,IL-52621 TEL HASHOMER,ISRAEL. YALE UNIV,SCH MED,BOYER CTR MOLEC MED,NEW HAVEN,CT 06536. UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR,DALLAS,TX 75235. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90095. UNIV ROMA LA SAPIENZA,DIPARTIMENTO MED SPERIMENTALE,I-00161 ROME,ITALY. HACETTEPE UNIV,FAC MED,DEPT PEDIAT,ANKARA 06100,TURKEY. QUEENSLAND INST MED RES,HERSTON,QLD 4006,AUSTRALIA. ERASMUS UNIV ROTTERDAM,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS. UNIV BIRMINGHAM,CRC,INST CANC STUDIES,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Lavin, Martin/F-5961-2014 OI Lavin, Martin/0000-0002-5940-4769 FU NHGRI NIH HHS [HG00882]; NINDS NIH HHS [NS31763] NR 68 TC 1930 Z9 1973 U1 3 U2 53 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 23 PY 1995 VL 268 IS 5218 BP 1749 EP 1753 DI 10.1126/science.7792600 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RE668 UT WOS:A1995RE66800042 PM 7792600 ER PT J AU BESSEN, RA KOCISKO, DA RAYMOND, GJ NANDAN, S LANSBURY, PT CAUGHEY, B AF BESSEN, RA KOCISKO, DA RAYMOND, GJ NANDAN, S LANSBURY, PT CAUGHEY, B TI NONGENETIC PROPAGATION OF STRAIN-SPECIFIC PROPERTIES OF SCRAPIE PRION PROTEIN SO NATURE LA English DT Article ID TRANSMISSIBLE MINK ENCEPHALOPATHY; DISEASES; BIOLOGY; MODEL; AGENT AB THE infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc)(1-6). One unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in PrPSc structure(2,7,8), rather than mutations in an agent-specific nucleic acid(9). Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME)(7,8), a a scrapie-like disease originating in mink. Although HY and DY PrPSc are both post-translationally derived from the precursor prion protein (PrPc) they are cleaved at different amino-terminal sites by proteinase K (ref. 8). Here we investigate whether this strain-specific property of PrPSc is transmitted to PrPc during formation of new PrPSc. PrPSc from the HY and DY TME strains converted the protease-sensitive PrPc into two distinct sets of protease-resistant PrP products in a cell-free system. These data provide evidence that self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. RP BESSEN, RA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 14 TC 390 Z9 398 U1 0 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 22 PY 1995 VL 375 IS 6533 BP 698 EP 700 DI 10.1038/375698a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RE576 UT WOS:A1995RE57600065 PM 7791905 ER PT J AU ARTHUR, LO HENDERSON, LE BENVENISTE, RE AF ARTHUR, LO HENDERSON, LE BENVENISTE, RE TI HUMAN-IMMUNODEFICIENCY-VIRUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID PROTEINS RP ARTHUR, LO (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 4 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 JUN 22 PY 1995 VL 332 IS 25 BP 1719 EP 1719 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RD996 UT WOS:A1995RD99600027 PM 7760882 ER PT J AU SEDDON, JM WILLETT, W SPERDUTO, RD AF SEDDON, JM WILLETT, W SPERDUTO, RD TI DIETARY CAROTENOIDS, VITAMIN-A, VITAMIN-C, AND VITAMIN-E, AND MACULAR DEGENERATION - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP SEDDON, JM (reprint author), NEI,EYE DIS CASE CONTROL STUDY GRP,BETHESDA,MD 20892, USA. NR 1 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 JUN 21 PY 1995 VL 273 IS 23 BP 1835 EP 1835 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RD116 UT WOS:A1995RD11600020 ER PT J AU ZAMETKIN, AJ AF ZAMETKIN, AJ TI ATTENTION-DEFICIT DISORDER - BORN TO BE HYPERACTIVE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID PSYCHIATRIC STATUS; THYROID-HORMONE; CHILDREN; RESISTANCE; METABOLISM; FAMILIES; BOYS RP ZAMETKIN, AJ (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 4N317,10 CTR DR MSC 1384,BETHESDA,MD 20892, USA. NR 34 TC 19 Z9 19 U1 1 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 JUN 21 PY 1995 VL 273 IS 23 BP 1871 EP 1874 DI 10.1001/jama.273.23.1871 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RD116 UT WOS:A1995RD11600031 PM 7776505 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI AUDIO-FREQUENCY NMR IN A NUTATING FRAME - APPLICATION TO THE ASSIGNMENT OF PHENYLALANINE RESIDUES IN ISOTOPICALLY ENRICHED PROTEINS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CORRELATION SPECTROSCOPY; POLARIZATION TRANSFER; MULTIDIMENSIONAL NMR; PROTON CORRELATION; COHERENCE TRANSFER; ENHANCEMENT; COUPLINGS; SIGNALS AB The effect of chemical shift can be removed to high order by quantizing nuclear spins along a strong radio-frequency (RF) field and applying a second audio-frequency magnetic field, orthogonal to the direction of the effective RF spin lock field. By adjusting the audio-modulation frequency of this second magnetic field to the rate at which spins nutate about the RF field, a resonance condition in the spin-locked frame is established which, to second order, is independent of the resonance offset of the homonuclear spins. The phase and amplitude of the audio-frequency field are under operator control and make it possible to conduct complex pulse sequences in the nutating frame. The approach is demonstrated for transferring in a single step magnetization from phenylalanine C-13(beta) to all aromatic ring carbons in a sample of uniformly C-13-enriched calmodulin. A three-dimensional version of the experiment yields complete resonance assignments for the structurally informative aromatic Phe signals, including all C-13(zeta) and H-1(zeta) resonances. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 22 TC 25 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 21 PY 1995 VL 117 IS 24 BP 6527 EP 6531 DI 10.1021/ja00129a016 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA RE575 UT WOS:A1995RE57500016 ER PT J AU RHYU, MS AF RHYU, MS TI TELOMERES, TELOMERASE, AND IMMORTALITY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TERMINAL TRANSFERASE; HUMAN FIBROBLASTS; TETRAHYMENA; REPEAT; SEQUENCES; CELLS; RNA; DNA; RIBONUCLEOPROTEIN; CHROMOSOMES AB A current hypothesis gaining prominence proposes that activation of the enzyme telomerase is necessary for cells to become immortal, or capable of proliferating indefinitely. The theory suggests that almost all cancer cells must attain immortality for progression to malignant states and, hence, require activation of telomerase. This article reviews the function and formation of telomeres as background to evaluating the ''telomere hypothesis.'' Experiments in support of and experiments that challenge the hypothesis are examined. Possible approaches to telomerase inhibition are discussed. RP RHYU, MS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 57 TC 349 Z9 383 U1 1 U2 16 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 JUN 21 PY 1995 VL 87 IS 12 BP 884 EP 894 DI 10.1093/jnci/87.12.884 PG 11 WC Oncology SC Oncology GA RD282 UT WOS:A1995RD28200011 PM 7666477 ER PT J AU KATO, S BOWMAN, ED HARRINGTON, AM BLOMEKE, B SHIELDS, PG AF KATO, S BOWMAN, ED HARRINGTON, AM BLOMEKE, B SHIELDS, PG TI HUMAN LUNG CARCINOGEN-DNA ADDUCT LEVELS MEDIATED BY GENETIC POLYMORPHISMS IN-VIVO SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; FRAGMENT-LENGTH-POLYMORPHISM; CYTOCHROME-P450 CYP2D LOCUS; SQUAMOUS-CELL CARCINOMA; CANCER SUSCEPTIBILITY; METABOLIC PHENOTYPE; CIGARETTE-SMOKING; CYP1A1 GENE; CLASS-MU; POPULATION AB Background: Cancer risk from exposure to tobacco smoke varies widely from person to person, depending in part on the status of particular genes and acquired susceptibilities. Certain genes determine how cells activate and detoxify carcinogens, Activated carcinogen metabolites may bind to DNA and form DNA adducts (e.g., 7-methyl-2'-deoxyguanosine-3'-monophosphate [7-methyl-dGMP] and polycyclic aromatic hydrocarbons-dGMP [PAHs-dGMP]), many of which can induce genetic mutations. Thus, if individuals have an increased capacity to activate carcinogens, they might form more carcinogen-DNA adducts and subsequently have an increased risk of cancer. Purpose: Using DNA-adduct detection methods specific for 7-methyl-dGMP and PAH-dGMP, we sought to determine whether an inherited genetic susceptibility to cancer associated with certain carcinogen-metabolizing and detoxifying genes (e.g., cytochrome P450 and glutathione S-transferase) is related to DNA adduct formation in lung tissue. Methods: Human lung tissues were collected randomly from 90 autopsy donors who were free of cancer. Levels of 7-methyl-dGMP, a metabolic product of N-nitrosamines, and PAH-dGMP adducts were determined in lung tissue specimens by use of micropreparative DNA purification steps combined with a P-32-postlabeling assay. Genetic polymorphisms (the presence of different genes and/or alleles) mere determined for the cytochrome P450 genes, CYP2D6, CYP2E1, and CYP1A1, as well as for glutathione S-transferase M1 (GSTM1). Statistical differences among adduct levels for the study variables, including genotypes, were assessed by the two-sided Student's t test or the Mann-Whitney U test. Results: Higher 7-methyl-dGMP adduct levels were associated with CYP2D6 genotypes (P = .01), consistent with the reports of the increased risk of lung cancer associated with this genotype. Higher adduct levels were also associated with CYP2E1 minor alleles (P = .05). In both cases, the association was attributed mostly to individuals with low serum cotinine levels (P = .004 and P = .05, respectively), suggesting that the effect of the genotypes is mostly in nonsmokers exposed to either passive tobacco smoke or to N-nitrosamine exposures other than tobacco smoke. Separately, the presence of PAH-dGMP adducts was associated with the GSTM1 null genotype (absence of the gene) (odds ratio = 8.6; 95% confidence interval = 1.03-100), Conclusions: This study finds that the levels of two different carcinogen-DNA adducts vary in lung tissue (an important target tissue) in association with three separate genetic polymorphisms (i.e., CYP2D6, CYP2E1, and GSTM1), CYP2D6 and CYP2E1 genotypes are associated with higher 7-methyl-dGMP levels, while the GSTM1 null genotype is associated with higher numbers of PAH-dGMP adducts. These findings suggest that genetic polymorphisms are predictive of carcinogen-DNA adduct levels and would thus be predictive of an individual's lifetime response to carcinogen exposure. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Shields, Peter/I-1644-2012 NR 43 TC 180 Z9 183 U1 0 U2 3 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 JUN 21 PY 1995 VL 87 IS 12 BP 902 EP 907 DI 10.1093/jnci/87.12.902 PG 6 WC Oncology SC Oncology GA RD282 UT WOS:A1995RD28200013 PM 7666479 ER PT J AU CNATTINGIUS, S ZACK, MM EKBOM, A GUNNARSKOG, J KREUGER, A LINET, M ADAMI, HO AF CNATTINGIUS, S ZACK, MM EKBOM, A GUNNARSKOG, J KREUGER, A LINET, M ADAMI, HO TI PRENATAL AND NEONATAL RISK-FACTORS FOR CHILDHOOD LYMPHATIC-LEUKEMIA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BIRTH-WEIGHT; VITAMIN-K; CANCER; EXPOSURE; EPIDEMIOLOGY AB Background: Because the incidence of childhood acute lymphatic leukemia peaks between 2 and 4 years of age, the risk factors may exert their influence during the prenatal and/or the neonatal periods. Results of previous studies of perinatal risk factors have been contradictory, perhaps because most studies either have been hospital based or have been restricted to limited geographical areas. Purpose: A nationwide case-control study was carried out to identify maternal and perinatal risk factors for this disease. Methods: The case-control study was nested in cohorts defined by all live births in Sweden recorded in the nationwide Medical Birth Register. Since 1973, this register has routinely collected information on all hospital births in regard to maternal demographic data, reproductive history, pregnancy, delivery, and the neonatal period. From the Swedish National Cancer Register, 613 case subjects were identified in successive birth cohorts from 1973 through 1989. Five control subjects per case subject were randomly selected from the pool of children matched by sex and month and year of birth, Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors and to estimate their effects after adjustment for possible confounders. Results: Risk of childhood lymphatic leukemia at all ages increased with Down's syndrome (OR = 20.0; 95% CI = 4.2-94.2), maternal renal disease (OR = 4.4; 95% CI = 1.6-12.1), use of supplementary oxygen (OR = 23; 95% CI = 1.5-3.6), postpartum asphyxia (OR = 1.8; 95% CI = 1.2-2.6), birth weight of more than 4500 g (OR = 1.7; 95% CI = 1.1-2.7), and hypertensive disease during pregnancy (OR = 1.4; 95% CI = 1.0-1.9). Down's syndrome affected risk mostly in children younger than 5 years, whereas other factors affected those children 5 years old or older. Being one of a multiple birth also increased risk among older children (OR = 2.5; 95% CI = 1.0-6.0). Use of supplementary oxygen may act as a causal intermediate (surrogate) for postpartum asphyxia and its causes, as would high birth weight for its causes. Conclusions: Several maternal and perinatal risk factors were found to be associated with childhood lymphatic leukemia, but they showed age-specific differences, Overall, only a few risk factors were identified, and these accounted for a small proportion of cases, We concluded that most risk factors for childhood lymphatic leukemia remain unidentified in very young children. C1 UNIV UPPSALA,UNIV HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. UNIV UPPSALA,UNIV HOSP,DEPT PEDIAT,S-75185 UPPSALA,SWEDEN. CTR DIS CONTROL & PREVENT,DIV CHRON DIS CONTROL & COMMUNITY INTERVENT,ATLANTA,GA 30341. NATL BOARD HLTH & WELF,CTR EPIDEMIOL,STOCKHOLM,SWEDEN. NATL CANC INST,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP CNATTINGIUS, S (reprint author), UNIV UPPSALA,UNIV HOSP,DEPT SOCIAL MED,S-75185 UPPSALA,SWEDEN. NR 34 TC 102 Z9 103 U1 0 U2 3 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 JUN 21 PY 1995 VL 87 IS 12 BP 908 EP 914 DI 10.1093/jnci/87.12.908 PG 7 WC Oncology SC Oncology GA RD282 UT WOS:A1995RD28200014 PM 7666480 ER PT J AU HEYWOOD, GR ROSENBERG, SA WEBER, JS AF HEYWOOD, GR ROSENBERG, SA WEBER, JS TI HYPERSENSITIVITY REACTIONS TO CHEMOTHERAPY AGENTS IN PATIENTS RECEIVING CHEMOIMMUNOTHERAPY WITH HIGH-DOSE INTERLEUKIN-2 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACTIVATED KILLER CELLS; PURIFIED HUMAN INTERLEUKIN-2; PHASE-I-II; RECOMBINANT INTERLEUKIN-2; METASTATIC MELANOMA; ADOPTIVE IMMUNOTHERAPY; CANCER-PATIENTS; SEQUENTIAL CHEMOIMMUNOTHERAPY; CONTRAST-MEDIA; THERAPY AB Background: Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. Purpose: In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. Methods: During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2), Twelve patients were treated in a nonrandomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU), Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches, In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. Results: Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritis, erythema, and edema to hypotension with hemodynamic instability that required presser therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions, All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. Conclusions: Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2 induced hypersensitivity to chemotherapy agents. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NR 53 TC 21 Z9 21 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 JUN 21 PY 1995 VL 87 IS 12 BP 915 EP 922 DI 10.1093/jnci/87.12.915 PG 8 WC Oncology SC Oncology GA RD282 UT WOS:A1995RD28200015 PM 7666481 ER PT J AU CHOW, WH GRIDLEY, G NYREN, O LINET, MS EKBOM, A FRAUMENI, JF ADAMI, HO AF CHOW, WH GRIDLEY, G NYREN, O LINET, MS EKBOM, A FRAUMENI, JF ADAMI, HO TI RISK OF PANCREATIC-CANCER FOLLOWING DIABETES-MELLITUS - A NATIONWIDE COHORT STUDY IN SWEDEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID BEVERAGE CONSUMPTION; MORTALITY; CARCINOMA; GLUCOSE; MEN RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN-415,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 20 TC 76 Z9 85 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 JUN 21 PY 1995 VL 87 IS 12 BP 930 EP 931 DI 10.1093/jnci/87.12.930 PG 2 WC Oncology SC Oncology GA RD282 UT WOS:A1995RD28200017 PM 7666483 ER PT J AU BHAGWAT, SV BOYD, MR RAVINDRANATH, V AF BHAGWAT, SV BOYD, MR RAVINDRANATH, V TI BRAIN MITOCHONDRIAL CYTOCHROMES P450 - XENOBIOTIC METABOLISM, PRESENCE OF MULTIPLE FORMS AND THEIR SELECTIVE INDUCIBILITY SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID O-DEETHYLASE ACTIVITY; RAT-BRAIN; SUBCELLULAR-DISTRIBUTION; SYSTEM; AFLATOXIN-B1; ACTIVATION; ETHANOL; PROTEIN; BINDING; MICROSOMES AB The capability of rat brain mitochondria to metabolize a variety of xenobiotics was examined. The presence of cytochrome P450 (P450) and associated monooxygenase activities were estimated in isolated rat brain mitochondria and compared with the corresponding activities in microsomes. Total P450 content in brain mitochondria from naive rats was twice that of the corresponding microsomal level. The ability of brain mitochondria to metabolize the potent carcinogen N-nitrosodimethylamine was more than twofold that of the corresponding microsomal activity, while the 7-ethoxycoumarin-O-deethylase activity was significantly lower in mitochondria. Immunoblot experiments using antisera to purified rat liver microsomal P450s, namely P450 (2B1/2B2), P450LA1, and P4502E1, and purified phenobarbital-inducible rat brain P450, revealed the presence of immunoreactive bands in isolated brain mitochondria. These various antibodies to P450 inhibited the brain mitochondrial monooxygenase activities to significant, though varying extent. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450 associated monooxygenase activities, although it completely inhibited the corresponding microsomal activities. Chronic ethanol administration resulted in twofold induction of total P450 content and the monooxygenase activities known to be mediated by P4502E1, such as N-nitrosodimethylamine-N-demethylase and p-nitrophenol hydroxylase in brain mitochondria. Pretreatment of animals with phenobarbital resulted in the induction of aminopyrine N-demethylase activity in brain mitochondria. The study demonstrates the presence of multiple forms of P450 in the rat brain mitochondria, their inducibility, and their capability to metabolize xenobiotics. (C) 1995 Academic Press, Inc. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 32 TC 53 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 20 PY 1995 VL 320 IS 1 BP 73 EP 83 DI 10.1006/abbi.1995.1344 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RE632 UT WOS:A1995RE63200009 PM 7793987 ER PT J AU CAO, GH CUTLER, RG AF CAO, GH CUTLER, RG TI PROTEIN OXIDATION AND AGING .1. DIFFICULTIES IN MEASURING REACTIVE PROTEIN CARBONYLS IN TISSUES USING 2,4-DINITROPHENYLHYDRAZINE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID GLUTAMINE-SYNTHETASE; DAMAGE; BRAIN AB A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This hypothesis is based on a series of reports showing an age-dependent increase in protein carbonyl content and an age-dependent loss of enzyme function, This hypothesis is also supported by the report of a novel effect of N-tert-butyl-a-phenylnitrone (PEN) in reversing these age-dependent changes. Here we specifically study the method that was used to measure reactive protein carbonyls in tissues. This method uses 2,4-dinitrophenylhydrazine (DNPH) and includes a washing procedure. Our results indicate that reactive protein carbonyls in normal crude tissue extracts cannot be reliably measured by this method, although it does reliably measure reactive carbonyls in purified proteins which have been oxidatively modified in vitro. The nucleic acids in tissues could be a major problem encountered in the assay. Using the streptomycin sulfate treatment combined with a dialysis step, we were successful in removing most nucleic acids from a crude tissue extract, but then the reactive carbonyl level in the crude tissue extract was too low to be reliably measured. This streptomycin sulfate treatment procedure, however, had no effect on the reactive carbonyl measurement of an oxidized protein sample. The unwashed free DNPH was another major problem in the assay because of its very strong absorption around 370 nm, where reactive carbonyls were quantitated. Nevertheless, on using the procedure described in the Literature to measure total ''reactive carbonyls'' in rat liver and gerbil brain cortex, no change with age or PEN treatment was found. Then, we investigated a HPLC procedure which uses sodium dodecyl sulfate in the mobile phase but this was also found to be unsuitable for the reactive protein carbonyl assay in tissues. (C) 1995 Academic Press, Inc. C1 NIA,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,BALTIMORE,MD 21224. NR 20 TC 116 Z9 118 U1 6 U2 15 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 20 PY 1995 VL 320 IS 1 BP 106 EP 114 DI 10.1006/abbi.1995.1347 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RE632 UT WOS:A1995RE63200012 PM 7793968 ER PT J AU CAO, GH CUTLER, RG AF CAO, GH CUTLER, RG TI PROTEIN OXIDATION AND AGING .2. DIFFICULTIES IN MEASURING ALKALINE PROTEASE ACTIVITY IN TISSUES USING THE FLUORESCAMINE PROCEDURE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE ALKALINE PROTEASE; MULTICATALYTIC PROTEINASE; PROTEIN OXIDATION; AGING; N-TERT-BUTYL-ALPHA-PHENYLNITRONE ID METAL-CATALYZED OXIDATION; GLUTAMINE-SYNTHETASE; MULTICATALYTIC PROTEINASE; CYSTEINE PROTEINASE; DEGRADATION; DAMAGE; CELLS AB A current hypothesis explaining the aging process implicates the accumulation of oxidized protein in animal tissues. This is primarily based on a series of reports showing an age-dependent increase in protein carbonyl content and an age-dependent decrease in the activities of enzymes, especially of alkaline proteases, which preferentially degrade oxidatively modified protein. Recently, this hypothesis was strongly supported by the report of a novel effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PEN) in reversing these age-dependent changes. However, we found that the reactive protein carbonyls could not be reliably measured in tissues by using the 2,4-dinitrophenylhydrazine procedure described in the PBN study. We now focus on the alkaline protease activity assay and show that alkaline protease activity cannot be reliably measured in crude tissue extracts by using the fluorescamine procedure also described in the PBN study. We were, however, able to reliably measure a protease activity in crude tissue extracts at alkaline pH by using a synthetic fluorogenic peptide substrate, but no effect of aging or PBN treatment was found on the protease activity in rat brain cortexes. Thus, the reported age-dependent changes in protein carbonyl formation and alkaline protease activity remain to be confirmed. (C) 1995 Academic Press, Inc. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. NR 18 TC 25 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 20 PY 1995 VL 320 IS 1 BP 195 EP 201 DI 10.1006/abbi.1995.1359 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RE632 UT WOS:A1995RE63200024 PM 7793980 ER PT J AU RETTIE, AE SHEFFELS, PR KORZEKWA, KR GONZALEZ, FJ PHILPOT, RM BAILLIE, TA AF RETTIE, AE SHEFFELS, PR KORZEKWA, KR GONZALEZ, FJ PHILPOT, RM BAILLIE, TA TI CYP4 ISOZYME SPECIFICITY AND THE RELATIONSHIP BETWEEN OMEGA-HYDROXYLATION AND TERMINAL DESATURATION OF VALPROIC ACID SO BIOCHEMISTRY LA English DT Article ID 2-NORMAL-PROPYL-4-PENTENOIC ACID; METABOLIC-ACTIVATION; TOXIC METABOLITE; LIVER MICROSOMES; RAT-LIVER; CYTOCHROME-P-450; OXIDATION; DEHYDROGENATION; INVITRO; LUNG AB The cytochrome P450-dependent terminal desaturation of valproic acid (VPA) is of both toxicological and mechanistic interest because the product, 4-ene-VPA, is a more potent hepatotoxin than the parent compound and its generation represents a rather novel metabolic reaction for the cytochrome P450 system. In the present study, lung microsomes from rabbits were identified as a rich source of VPA desaturase activity. Monospecific polyclonal antibodies directed against CYP4B1 (anti-4B) inhibited 82% of 4-ene-VPA formation, whereas monospecific polyclonal antibodies directed against CYP2B4 (anti-2B) inhibited only 15% of 4-ene-VPA formation. Anti-4B also inhibited 95% of the 5-hydroxy-VPA formation, but only 42% of LF-hydroxy-VPA formation. These data suggest that CYP4B1 accounts for more than 80% of the 4-ene- and 5-hydroxy-VPA metabolites generated by rabbit lung microsomes. CYP4B1 expressed in HepG2 cells metabolized VPA with a turnover number of 35 min(-1) and formed the 5-hydroxy-, 4-hydroxy-, and 4-ene-VPA metabolites in a ratio of 110:2:1, respectively. In contrast, the lauric acid omega-hydroxylases, CYP4A1 and CYP4A3, did not give rise to detectable levels of any of these VPA metabolites. Therefore, these studies demonstrate a new functional role for CYP4B1 in the terminal desaturation and omega-hydroxylation of this short, branched-chain fatty acid. Intramolecular deuterium isotope effects on the formation of 4-ene-VPA, 4-hydroxy-VPA, and 5-hydroxy-VPA by cDNA-expressed CYP4B1 and by purified, reconstituted CYP2B1 indicate that a carbon-centered free radical at C-4 serves as a common intermediate for P450-dependent formation of both 4-ene-VPA and 4-hydroxy-VPA, regardless of whether the enzyme source functions preferentially as an omega-hydroxylase or an omega-1 hydroxylase of VPA. The partition between oxygen rebound to, and desaturation proceeding from, the C-4 VPA radical was 2:1 for CYP4B1 and 37:1 for the VPA 4-hydroxylase CYP2B1. Therefore, active site constraints which promote facile omega-hydroxylation bias the partition ratio toward desaturation and significantly enhance the rate of P450-dependent 4-ene-VPA formation. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIEHS,COMPARAT MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP RETTIE, AE (reprint author), UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195, USA. FU NIGMS NIH HHS [GM32165, GM49054] NR 43 TC 61 Z9 62 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 20 PY 1995 VL 34 IS 24 BP 7889 EP 7895 DI 10.1021/bi00024a013 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE645 UT WOS:A1995RE64500013 PM 7794900 ER PT J AU BLANAR, MA CROSSLEY, PH PETERS, KG STEINGRIMSSON, E COPELAND, NG JENKINS, NA MARTIN, GR RUTTER, WJ AF BLANAR, MA CROSSLEY, PH PETERS, KG STEINGRIMSSON, E COPELAND, NG JENKINS, NA MARTIN, GR RUTTER, WJ TI MESO1, A BASIC-HELIX-LOOP-HELIX PROTEIN INVOLVED IN MAMMALIAN PRESOMITIC MESODERM DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENETIC-LINKAGE MAP; DNA-BINDING; MOUSE EMBRYO; EXPRESSION; MOTIF; ORGANOGENESIS; ORGANIZATION; GASTRULATION; MYOGENESIS; ENHANCER AB To identify genes involved in the regulation of early mammalian development, we have developed a dominant-negative mutant basic-helix-loop-helix (bHLH) protein probe for interaction cloning and have isolated a member of the bHLH family of transcription factors, Meso1. Meso1-E2A heterodimers are capable of binding to oligonucleotide probes that contain a bHLH DNA recognition motif. In mouse embryos, Meso1 is expressed prior to MyoD1 family members. Meso1 expression is first detected at the neural plate stage of development in the paraxial mesoderm of the head and in presomitic mesodermal cells prior to their condensation into somites. Our findings suggest that Meso1 may be a key regulatory gene involved in the early events of vertebrate mesoderm differentiation. C1 UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,PROGRAM DEV BIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,INST CARDIOVASC RES,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,HORMONE RES INST,SAN FRANCISCO,CA 94143. RP BLANAR, MA (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,ROOM K-4125,MAIL CODE K14-01,ROUTE 206 & PROVINCE,PRINCETON,NJ 08543, USA. FU NICHD NIH HHS [HD-25331]; NIDDK NIH HHS [DK-41822, DK-21344] NR 27 TC 40 Z9 43 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 JUN 20 PY 1995 VL 92 IS 13 BP 5870 EP 5874 DI 10.1073/pnas.92.13.5870 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000024 PM 7597044 ER PT J AU SCHUTTE, M DACOSTA, LT HAHN, SA MOSKALUK, C HOQUE, ATMS ROZENBLUM, E WEINSTEIN, CL BITTNER, M MELTZER, PS TRENT, JM YEO, CJ HRUBAN, RH KERN, SE AF SCHUTTE, M DACOSTA, LT HAHN, SA MOSKALUK, C HOQUE, ATMS ROZENBLUM, E WEINSTEIN, CL BITTNER, M MELTZER, PS TRENT, JM YEO, CJ HRUBAN, RH KERN, SE TI IDENTIFICATION BY REPRESENTATIONAL DIFFERENCE ANALYSIS OF A HOMOZYGOUS DELETION IN PANCREATIC-CARCINOMA THAT LIES WITHIN THE BRCA2 REGION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN BREAST-CARCINOMA; CANCER; CLONING; GENE; ALLELOTYPE; HETEROZYGOSITY; DNA AB Homozygous deletions have been central to the discovery of several tumor-suppressor genes, but their finding has often been either serendipitous or the result of a directed search. A recently described technique [Lisitsyn, N., Lisitsyn, N. and Wigler, M. (1993) Science 259, 946-951] held out the potential to efficiently discover such events in an unbiased manner. Here we present the application of the representational difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q123 flanked by the markers D13S171 and D138260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the same gene may be involved in multiple tumor types and that its function is that of a tumor suppressor rather than that of a dominant oncogene. C1 JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DIV TOXICOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,PROGRAM HUMAN GENET,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Hahn, Stephan/E-3880-2010 FU NCI NIH HHS [CA56130, CA62924] NR 38 TC 143 Z9 150 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 20 PY 1995 VL 92 IS 13 BP 5950 EP 5954 DI 10.1073/pnas.92.13.5950 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000040 PM 7597059 ER PT J AU COHEN, OJ PANTALEO, G HOLODNIY, M SCHNITMAN, S NIU, M GRAZIOSI, C PAVLAKIS, GN LALEZARI, J BARTLETT, JA STEIGBIGEL, RT COHN, J NOVAK, R MCMAHON, D FAUCI, AS AF COHEN, OJ PANTALEO, G HOLODNIY, M SCHNITMAN, S NIU, M GRAZIOSI, C PAVLAKIS, GN LALEZARI, J BARTLETT, JA STEIGBIGEL, RT COHN, J NOVAK, R MCMAHON, D FAUCI, AS TI DECREASED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PLASMA VIREMIA DURING ANTIRETROVIRAL THERAPY REFLECTS DOWN-REGULATION OF VIRAL REPLICATION IN LYMPHOID-TISSUE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FOLLICULAR DENDRITIC CELLS; PLACEBO-CONTROLLED TRIAL; HIV-INFECTION; DOUBLE-BLIND; AIDS; ZIDOVUDINE; LYMPHADENOPATHY; EFFICACY; NODES; RNA AB Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for greater than or equal to 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. C1 DEPT VET AFFAIRS MED CTR,CTR AIDS RES,PALO ALTO,CA 94304. NIAID,DIV AIDS,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT MED,SAN FRANCISCO,CA 94115. DUKE UNIV,MED CTR,DIV INFECT DIS,DURHAM,NC 27710. SUNY STONY BROOK,MED CTR,DIV INFECT DIS,STONY BROOK,NY 11794. UNIV MARYLAND,MED CTR,DIV INFECT DIS,BALTIMORE,MD 21201. UNIV ILLINOIS,MED CTR,DIV INFECT DIS,CHICAGO,IL 60612. UNIV PITTSBURGH,MED CTR,DIV INFECT DIS,PITTSBURGH,PA 15213. RP COHEN, OJ (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,10 CTR DR,MSC 1876,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 FU NCI NIH HHS [N01-CO-46000] NR 33 TC 59 Z9 59 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 JUN 20 PY 1995 VL 92 IS 13 BP 6017 EP 6021 DI 10.1073/pnas.92.13.6017 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000054 PM 7597072 ER PT J AU JENKINS, TM HICKMAN, AB DYDA, F GHIRLANDO, R DAVIES, DR CRAIGIE, R AF JENKINS, TM HICKMAN, AB DYDA, F GHIRLANDO, R DAVIES, DR CRAIGIE, R TI CATALYTIC DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE - IDENTIFICATION OF A SOLUBLE MUTANT BY SYSTEMATIC REPLACEMENT OF HYDROPHOBIC RESIDUES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; DNA-BINDING; RETROVIRAL INTEGRATION; RNA-POLYMERASE; POL GENE; PROTEIN; INVITRO; SITE; RECOGNITION; EXPRESSION AB The integrase protein of human immunodeficiency virus type 1 is necessary for the stable integration of the viral genome into host DNA, Integrase catalyzes the 3' professing of the linear viral DNA and the subsequent DNA strand transfer reaction that inserts the viral DNA ends into host DNA, Although full-length integrase is required for 3' processing and DNA strand transfer activities in vitro, the central core domain of integrase is sufficient to catalyze an apparent reversal of the DNA strand transfer reaction, termed disintegration, This catalytic core domain, as well as the full-length integrase, has been refractory to structural studies by x-ray crystallography or NMR because of its low solubility and propensity to aggregate, In an attempt to improve protein solubility, we used site-directed mutagenesis to replace hydrophobic residues within the core domain with either alanine or lysine. The single substitution of lysine for phenylalanine at position 185 resulted in a core domain that was highly soluble, monodisperse in solution, and retained catalytic activity, This amino acid change has enabled the catalytic domain of integrase to be crystallized and the structure has been solved to 2,5-Angstrom resolution [Dyda, F., Hickman, A. B., Jenkins, T. M., Engelman, A., Craigie, R. and Davies, D. R. (1994) Science 266, 1981-1986]. Systematic replacement of hydrophobic residues may be a useful strategy to improve the solubility of other proteins to facilitate structural and biochemical studies. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009 NR 32 TC 121 Z9 126 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 20 PY 1995 VL 92 IS 13 BP 6057 EP 6061 DI 10.1073/pnas.92.13.6057 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000062 PM 7597080 ER PT J AU NAKAMURA, T PICHEL, JG WILLIAMSSIMONS, L WESTPHAL, H AF NAKAMURA, T PICHEL, JG WILLIAMSSIMONS, L WESTPHAL, H TI AN APOPTOTIC DEFECT IN LENS DIFFERENTIATION CAUSED BY HUMAN P53 IS RESCUED BY A MUTANT ALLELE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSGENIC MICE; DOMINANT NEGATIVE INTERFERENCE ID WILD-TYPE P53; TRANSGENIC MICE; BINDING PROTEIN; GENE; EXPRESSION; MUTATIONS; CANCER; LINE; IDENTIFICATION; TRANSCRIPTION AB If deprived of wild-type p53 function, the body loses a guardian that protects against cancer, Restoration of p53 function has, therefore, been proposed as a means of counteracting oncogenesis. This concept of therapy requires prior knowledge with regard to proper balance of p53 function in a given target tissue. We have addressed this problem by targeting expression of the wild-type human p53 gene to the lens, a tissue entirely composed of epithelial cells that differentiate into elongated fiber cells. Transgenic mice expressing wild-type human p53 develop microphthalmia as a result of a defect in fiber formation that sets in shortly after birth, We see apoptotic cells that fail to undergo proper differentiation. In an effort to directly link the observed lens phenotype to the activity of the wild-type human p53 transgene, me also generated mice expressing a mutant human p53 allele that lacks wild-type function. A normal lens phenotype is restored in double transgenic animals that carry both wild-type and mutant human p53 alleles. Our study highlights the difficulties that can arise if p53 levels are improperly balanced in a differentiating tissue. RP NAKAMURA, T (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,BETHESDA,MD 20892, USA. NR 43 TC 63 Z9 64 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 JUN 20 PY 1995 VL 92 IS 13 BP 6142 EP 6146 DI 10.1073/pnas.92.13.6142 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000079 PM 7597093 ER PT J AU BUCKHEIT, RW FLIAKASBOLTZ, V YEAGYBARGO, S WEISLOW, O MAYERS, DL BOYER, PL HUGHES, SH PAN, BC CHU, SH BADER, JP AF BUCKHEIT, RW FLIAKASBOLTZ, V YEAGYBARGO, S WEISLOW, O MAYERS, DL BOYER, PL HUGHES, SH PAN, BC CHU, SH BADER, JP TI RESISTANCE TO 1-[(2-HYDROXYETHOXY)METHYL]-6-(PHENYLTHIO)THYMINE DERIVATIVES IS GENERATED BY MUTATIONS AT MULTIPLE SITES IN THE HIV-1 REVERSE-TRANSCRIPTASE SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; HIV-1-SPECIFIC INHIBITORS; ANTIVIRAL ACTIVITY; TIBO DERIVATIVES; VIRAL RESISTANCE; DRUG; REPLICATION; SENSITIVITY; NEVIRAPINE AB Virus isolates resistant to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and a highly potent HEPT derivative, [1-benzyloxymethyl-5-ethyl-6-(alpha-pyridylthio)uracil] (NSC 648400, E-BPTU), were selected in cell culture. Cross-resistance evaluation indicated that the two drug-resistant virus isolates were phenotypically distinct from one another although each of the virus isolates was resistant to both of the HEPT derivatives. The virus isolate resistant to NSC 648400 had a single amino acid change in the reverse transcriptase (Y181C) which resulted in cross-resistance to all of the nonnucleoside reverse transcriptase inhibitors evaluated, with the exception of calanolide A. The NSC 648400-resistant virus isolate exhibited 15-fold enhanced sensitivity to calanolide A. The virus isolate selected in the presence of HEPT exhibited a single amino acid change (P236L) which was not cross-resistant to other nonnucleoside RT inhibitors tested with the exception of the two HEPT derivatives. This HEPT-resistant virus isolate exhibited enhanced sensitivity (5- to 10-fold) to thiazolobenzimidazole. We have used both virus isolates with defined single amino acid changes in the RT and bacterially expressed RTs with site-directed amino acid substitutions to test the effects of a wide variety of mutations on the activity of NSC 648400. Single mutations at amino acids 101, 103, 106, 181, or 236 yielded virus with high resistance (> 20)-fold) to NSC 648400, while lower levels of resistance were seen with mutations at amino acids 98, 100, or 108. These results suggest that several changes in the conformation of the nonnucleoside inhibitor binding site of the HIV-1 reverse transcriptase can affect the inhibitory activity of the HEPT class of compounds. (C) 1995 academic Press, Inc. C1 SPA TECHNOL INC,ROCKVILLE,MD 20850. WALTER REED ARMY INST RES,DEPT HIV DIS PREVENT,ROCKVILLE,MD 20850. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. RP BUCKHEIT, RW (reprint author), SO RES INST,FREDERICK RES CTR,VIROL RES GRP,431 AVIAT WAY,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CM-37818, CA 39427]; NIAID NIH HHS [N01-AI-05087] NR 40 TC 33 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1995 VL 210 IS 1 BP 186 EP 193 DI 10.1006/viro.1995.1330 PG 8 WC Virology SC Virology GA RE655 UT WOS:A1995RE65500020 PM 7540784 ER PT J AU WYATT, LS MOSS, B ROZENBLATT, S AF WYATT, LS MOSS, B ROZENBLATT, S TI REPLICATION-DEFICIENT VACCINIA VIRUS ENCODING BACTERIOPHAGE T7 RNA-POLYMERASE FOR TRANSIENT GENE-EXPRESSION IN MAMMALIAN-CELLS SO VIROLOGY LA English DT Note ID FOREIGN GENES; SYSTEM; SEQUENCE AB The vaccinia virus/bacteriophage T7 hybrid transient expression system employs a recombinant vaccinia virus that encodes the T7 RNA polymerase gene, a plasmid vector with a gene of interest regulated by a T7 promoter, and any cell line suitable for infection and transfection. Although high expression in a majority of cells is achieved, the severe cytopathic effects of vaccinia virus and the safety precautions required for use of infectious agents are undesirable features of the system. Here, we report the construction of a highly attenuated and avian host-restricted vaccinia virus recombinant that encodes the T7 RNA polymerase gene (MVA/T7 pol) and demonstrate the use of the virus for transient expression in mammalian cells. MVA/T7 pol has reduced cytopathic effects compared to the previously used replication-competent vaccinia virus, while providing a high level of gene expression in multiple mammalian cell lines. (C) 1995 Academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 15 TC 210 Z9 211 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1995 VL 210 IS 1 BP 202 EP 205 DI 10.1006/viro.1995.1332 PG 4 WC Virology SC Virology GA RE655 UT WOS:A1995RE65500022 PM 7793072 ER PT J AU ENSOLI, F CAFARO, A FIORELLI, V VANNELLI, B ENSOLI, B THIELE, CJ AF ENSOLI, F CAFARO, A FIORELLI, V VANNELLI, B ENSOLI, B THIELE, CJ TI HIV-1 INFECTION OF PRIMARY HUMAN NEUROBLASTS SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; CENTRAL-NERVOUS-SYSTEM; NEURONAL CELL-LINE; HUMAN GLIAL-CELLS; HTLV-III; PROGRESSIVE ENCEPHALOPATHY; PRODUCTIVE INFECTION; NEURAL CELLS; AIDS AB Central nervous system (CNS) disorders are frequent in HIV-1-infected individuals, particularly in newborns and children, and are accompanied by histological alterations resulting in neuronal loss. Although several tumor-derived neuroectodermal cell lines can be infected by HIV-I, it has been reported that primary neural cells cannot be infected after they differentiate. However, pediatric AIDS is often the result of HIV-1 infection occurring during fetal development and early postnatal life, when neural cells are not yet differentiated. Here we show that primary cell cultures derived from the human fetal olfactory system which are representative of the developing CNS can be infected by both HIV-1 strains, the monocyte-macrophagotropic Bat and the lymphotropic HTLV-IIIB, although they do not express the CD4 molecule. In addition, the levels of viral replication are higher with the HIV-1 Bat than with the IIIB isolate. These results suggest that (1) during development immature neurons are susceptible to HIV-1 infection; (2) monocyte-macrophagotropic HIV-1 strains may preferentially be involved in the productive infection of the nervous system; and (3) a mechanism(s) other than the CD4-mediated viral entry is responsible for HIV-1 infection of immature neurons. (C) 1995 Academic Press, Inc. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV FLORENCE,DEPT ANAT & HISTOL,FLORENCE,ITALY. RP ENSOLI, F (reprint author), NCI,PEDIAT BRANCH,CELL & MOLEC BIOL SECT,BLDG 10,BETHESDA,MD 20892, USA. RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016 OI Ensoli, Barbara/0000-0002-0545-8737; NR 46 TC 38 Z9 39 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1995 VL 210 IS 1 BP 221 EP 225 DI 10.1006/viro.1995.1336 PG 5 WC Virology SC Virology GA RE655 UT WOS:A1995RE65500026 PM 7793075 ER PT J AU MICHELINI, S URBANEK, M DEAN, M GOLDMAN, D AF MICHELINI, S URBANEK, M DEAN, M GOLDMAN, D TI POLYMORPHISM AND GENETIC-MAPPING OF THE HUMAN OXYTOCIN RECEPTOR GENE ON CHROMOSOME-3 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CA REPEATS; AFFILIATIVE BEHAVIORS; VHL ID VENTROMEDIAL HYPOTHALAMIC NUCLEUS; HORMONE BINDING-SITES; RAT-BRAIN; SOCIAL-ORGANIZATION; PITUITARY-GLAND; PRAIRIE VOLES; LONG-EVANS; LOCALIZATION; VASOPRESSIN; FOREBRAIN AB Centrally administered oxytocin has been reported to facilitate affiliative and social behaviours, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection, The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene, A portion of the 3' untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70), The CA repeat polymorphism we detected was used to map the the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. (C) 1995 Wiley-Liss, Inc. C1 NIAAA, NEUROGENET LAB, ROCKVILLE, MD 20852 USA. NCI, VIRAL CARCINOGENESIS LAB, FREDERICK, MD USA. UNIV PISA, INST PSYCHIAT, I-56100 PISA, ITALY. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 53 TC 35 Z9 35 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 19 PY 1995 VL 60 IS 3 BP 183 EP 187 DI 10.1002/ajmg.1320600303 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RD839 UT WOS:A1995RD83900002 PM 7573168 ER PT J AU ADAMSON, MD KENNEDY, J PETRONIS, A DEAN, M VIRKKUNEN, M LINNOILA, M GOLDMAN, D AF ADAMSON, MD KENNEDY, J PETRONIS, A DEAN, M VIRKKUNEN, M LINNOILA, M GOLDMAN, D TI DRD4 DOPAMINE-RECEPTOR GENOTYPE AND CSF MONOAMINE METABOLITES IN FINNISH ALCOHOLICS AND CONTROLS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ALCOHOLISM; DOPAMINE; DOPAMINE RECEPTOR; SEROTONIN; GENETIC ASSOCIATION; IMPULSIVITY ID IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; HOMOVANILLIC-ACID; VIOLENT OFFENDERS; NERVOUS-SYSTEM; AL ALLELE; GENE; ASSOCIATION; BRAIN AB The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. (C) 1995 Wiley-Liss, Inc. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROCKVILLE,MD 20852. CLARKE INST PSYCHIAT,TORONTO,ON M5T 1R8,CANADA. UNIV TORONTO,TORONTO,ON,CANADA. HELSINKI UNIV,DEPT PSYCHIAT,HELSINKI,FINLAND. RP ADAMSON, MD (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,NEUROGENET LAB,12501 WASHINGTON AVE,FLOW BLDG,ROCKVILLE,MD 20852, USA. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 52 TC 52 Z9 52 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 19 PY 1995 VL 60 IS 3 BP 199 EP 205 DI 10.1002/ajmg.1320600306 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RD839 UT WOS:A1995RD83900005 PM 7573171 ER PT J AU RAM, A CAO, QH KECK, PE POPE, HG OTANI, K ADDONIZIO, G MCELROY, SL KANEKO, S REDLICHOVA, M GERSHON, ES GEJMAN, PV AF RAM, A CAO, QH KECK, PE POPE, HG OTANI, K ADDONIZIO, G MCELROY, SL KANEKO, S REDLICHOVA, M GERSHON, ES GEJMAN, PV TI STRUCTURAL-CHANGE IN DOPAMINE D-2 RECEPTOR GENE IN A PATIENT WITH NEUROLEPTIC MALIGNANT SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE DOPAMINE D-2 RECEPTOR GENE; NEUROLEPTIC MALIGNANT SYNDROME; ANTIPSYCHOTIC DRUGS; MUTATIONAL ANALYSIS ID FREQUENCY; THERAPY; D2 AB Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome, Therefore, we examined the complete coding sequences of the dopamine D-2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS, Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences, We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. (C) 1995 Wiley-Liss, Inc. C1 NIMH,CLIN NEUROGENET BRANCH,MOLEC CLIN INVEST UNIT,BETHESDA,MD 20892. UNIV CINCINNATI,COLL MED,DEPT PSYCHIAT,BIOL PSYCHIAT PROGRAM,CINCINNATI,OH 45267. MCLEAN HOSP,BIOL PSYCHIAT LAB,BELMONT,MA 02178. HARVARD UNIV,SCH MED,BOSTON,MA. CORNELL UNIV,NEW YORK HOSP,CORNELL MED CTR,WESTCHESTER DIV,WHITE PLAINS,NY 10605. HIROSAKI UNIV HOSP,DEPT NEUROPSYCHIAT,HIROSAKI,AOMORI 036,JAPAN. NR 25 TC 19 Z9 20 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 JUN 19 PY 1995 VL 60 IS 3 BP 228 EP 230 DI 10.1002/ajmg.1320600311 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA RD839 UT WOS:A1995RD83900010 PM 7573176 ER PT J AU LEONARD, CM MARTINEZ, P WEINTRAUB, BD HAUSER, P AF LEONARD, CM MARTINEZ, P WEINTRAUB, BD HAUSER, P TI MAGNETIC-RESONANCE-IMAGING OF CEREBRAL ANOMALIES IN SUBJECTS WITH RESISTANCE TO THYROID-HORMONE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE HUMAN THYROID RECEPTOR BETA GENE; SYLVIAN FISSURE MORPHOLOGY ID GENERALIZED RESISTANCE; GENE-EXPRESSION; BRAIN; DISORDERS; INTERVIEW; CHILDREN; RECEPTOR AB Objective. Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3, Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD), The purpose of this study was to search for developmental brain malformations associated with RTH. Method. Forty-three subjects (20 affected males [ARM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images, Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl's transverse gyri (primary auditory cortex) were noted. Results. There was a significantly increased frequency of anomalous Sylvian fissures in the left hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%), Also, there was an increased frequency of anomalous Sylvian fissures on the left combined with multiple Heschl's gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%; UM: 6%; UF: 0%), However, RTH subjects with anomalies did not have an increased frequency of ADHD as compared with RTH subjects with no anomalies. Conclusions. Abnormal thyroid hormone action in the male fetus early during brain development may be associated with grossly observable cerebral anomalies of the left hemisphere, The effects of mutations in the thyroid receptor beta gene provide a model system for studying the complex interaction of genetic and nongenetic factors on brain and behavioral development. (C) 1995 Wiley Liss, Inc.* C1 UNIV FLORIDA,CTR HLTH SCI,DEPT NEUROSCI,GAINESVILLE,FL. UNIV FLORIDA,CTR HLTH SCI,DEPT PSYCHIAT,GAINESVILLE,FL. NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD. VET AFFAIRS MED CTR,PSYCHIAT SERV,BALTIMORE,MD 21201. NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. NR 19 TC 21 Z9 21 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 JUN 19 PY 1995 VL 60 IS 3 BP 238 EP 243 DI 10.1002/ajmg.1320600314 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RD839 UT WOS:A1995RD83900013 PM 7573179 ER PT J AU JAARSMA, D WENTHOLD, RJ MUGNAINI, E AF JAARSMA, D WENTHOLD, RJ MUGNAINI, E TI GLUTAMATE-RECEPTOR SUBUNITS AT MOSSY FIBER-UNIPOLAR BRUSH CELL SYNAPSES - LIGHT AND ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMICAL STUDY IN CEREBELLAR CORTEX OF RAT AND CAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE AMPA; KAINATE; NMDA; PURKINJE CELL; GRANULE CELL ID METHYL-D-ASPARTATE; NMDA RECEPTOR; HIGH-AFFINITY; SUBCELLULAR-LOCALIZATION; MONOCLONAL-ANTIBODIES; GRANULE CELLS; BRAIN; KAINATE; CHANNELS; IMMUNOREACTIVITY AB The present study provides a survey of the immunolocalization of ionotropic glutamate receptor subunits throughout the rat and cat cerebellar cortex, with emphasis on the unipolar brush cell (UBC), a hitherto neglected cerebellar cell that is densely concentrated in the granular layer of the vestibulocerebellum and that forms giant synapses with messy fibers. An array of nine previously characterized antibodies has been used, each of which stained a characteristic profile of cerebellar cells. The UBCs of both rat and cat were strongly immunostained by an antibody against the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate ate (AMPA) receptor subunits, GluR2 and GluR3; were moderately immunostained by a monoclonal antibody to kainate receptor subunits, GluR5/6/7; were weakly immunostained by antibodies to NR1 subunits; and were not stained by antibodies to GluR1, GluR4, GluR6/7, KA-2, and NR2A/B. Postsynaptic densities of the giant massy fiber-UBC synapses were GluR2/3, GluR5/6/7, and NR1 immunoreactive. The other cerebellar neurons were all immunolabeled to some extent with the GluR2/3 and NR1 antibodies. In addition, Purkinje cells were immunopositive for GluR1 and GluR5/6/7; granule cells were immunopositive for GluR5/6/7, GluR6/7, KA-2, and NR2A/B. The Golgi-Bergmann glia was densely stained by GluR1 and GluR4 antibodies, whereas astrocytes of the granular layer were stained by the GluR4 antiserum. Data provided herein may guide further electrophysiological and pharmacological studies of cerebellar cells in general and the UBCs in particular. (C) 1995 Wiley-Liss, Inc. C1 UNIV CONNECTICUT,BIOBEHAV SCI GRAD PROGRAM U154,NEUROMORPHOL LAB,STORRS,CT 06269. NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 09904] NR 69 TC 56 Z9 56 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 19 PY 1995 VL 357 IS 1 BP 145 EP 160 DI 10.1002/cne.903570113 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RC942 UT WOS:A1995RC94200012 PM 7673463 ER PT J AU PONTIERI, FE VIOLA, JJ SOKOLOFF, L PORRINO, LJ AF PONTIERI, FE VIOLA, JJ SOKOLOFF, L PORRINO, LJ TI SELECTIVE METABOLIC-ACTIVATION BY APOMORPHINE IN STRIOSOMES OF DENERVATED STRIATUM IN MPTP-INDUCED HEMIPARKINSONIAN MONKEYS SO NEUROREPORT LA English DT Article DE APOMORPHINE; DEOXYGLUCOSE; MPTP; DOPAMINE; STRIOSOMES; MATRIX ID CEREBRAL GLUCOSE-UTILIZATION; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; INFUSION AB RESULTS of previous studies have suggested differences in the regulatory mechanisms in striatal striosomes and matrix following interruption of dopaminergic input to the striatum by MPTP in the monkey. In the present study we have investigated the possibility that stimulation of dopamine receptors by apomorphine modifies glucose metabolism differentially in the two striatal compartments of unilaterally MPTP-lesioned monkeys. Apomorphine treatment was found to result in higher rates of glucose utilization in the denervated striatum than in the intact hemisphere. Furthermore, the effect was more robust in the striosomes than in the matrix, thus providing evidence for differential functional and/or metabolic regulation in striatal striosomes and matrix in parkinsonian syndromes. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,WINSTON SALEM,NC 27157. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DIPARTIMENTO SCI NEUROL,ROME,ITALY. GEORGETOWN UNIV,SCH MED,DEPT NEUROSURG,WASHINGTON,DC. NR 14 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 19 PY 1995 VL 6 IS 9 BP 1330 EP 1332 PG 3 WC Neurosciences SC Neurosciences & Neurology GA RG170 UT WOS:A1995RG17000025 PM 7669997 ER PT J AU GRAM, TE AF GRAM, TE TI METABOLIC-ACTIVATION AND TOXICITY OF SOME CHEMICAL-AGENTS TO LUNG-TISSUE AND CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE LUNG TOXICITY; COVALENT BINDING; METABOLIC ACTIVATION; CHEMICALLY REACTIVE METABOLITES; BENZO[A]PYRENE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK); 2-(2-CHLOROPHENYL)-2-(4-CHLOROPHENYL)-1,1-DICHLOROETHANE (O,P'-DDD) ID A/J MOUSE LUNG; CARCINOGEN 4-(N-METHYL-N-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; COVALENT BINDING; DOSE-RESPONSE; NEWBORN MICE; F344 RATS; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; TUMORIGENICITY; DNA; NITROSODIMETHYLAMINE C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 28 TC 2 Z9 2 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 JUN 16 PY 1995 VL 49 IS 12 BP 1721 EP 1727 DI 10.1016/0006-2952(95)00012-O PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RG206 UT WOS:A1995RG20600001 PM 7598733 ER PT J AU ZHANG, GG KAZANIETZ, MG BLUMBERG, PM HURLEY, JH AF ZHANG, GG KAZANIETZ, MG BLUMBERG, PM HURLEY, JH TI CRYSTAL-STRUCTURE OF THE CYS2 ACTIVATOR-BINDING DOMAIN OF PROTEIN-KINASE C-DELTA IN COMPLEX WITH PHORBOL ESTER SO CELL LA English DT Article ID PROGRAM; REFINEMENT; ZINC AB Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with mai n-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes. C1 NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, MOLEC MECHANISMS TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. NR 23 TC 513 Z9 519 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 16 PY 1995 VL 81 IS 6 BP 917 EP 924 DI 10.1016/0092-8674(95)90011-X PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RD768 UT WOS:A1995RD76800012 PM 7781068 ER PT J AU VANGENT, DC MCBLANE, JF RAMSDEN, DA SADOFSKY, MJ HESSE, JE GELLERT, M AF VANGENT, DC MCBLANE, JF RAMSDEN, DA SADOFSKY, MJ HESSE, JE GELLERT, M TI INITIATION OF V(D)J RECOMBINATION IN A CELL-FREE SYSTEM SO CELL LA English DT Article ID RAG-1; GENES; MICE; DNA AB Cells performing V(D)J recombination make specific cuts in DNA at recombination signal sequences. Here, we show that nuclear extracts of pre-a cell lines carry out this specific cleavage. The products of cleavage are the same as found previously in thymocytes: full-length, blunt, 5'-phosphorylated signal ends, and covalently sealed (hairpin) coding ends. A complete signal sequence is required. Recombinant RAG1 protein greatly increases activity and complements an inactive extract from a RAG1 (-/-) pre-a cell line. When the extracts are fractionated, cleavage activity correlates with the presence of RAG2 protein. These results suggest that RAG1 and RAG2 are components of the V(D)J recombinase. RP VANGENT, DC (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 247 Z9 249 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 16 PY 1995 VL 81 IS 6 BP 925 EP 934 DI 10.1016/0092-8674(95)90012-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RD768 UT WOS:A1995RD76800013 PM 7781069 ER PT J AU FISHER, GH ROSENBERG, FJ STRAUS, SE DALE, JK MIDDELTON, LA LIN, AY STROBER, W LENARDO, MJ PUCK, JM AF FISHER, GH ROSENBERG, FJ STRAUS, SE DALE, JK MIDDELTON, LA LIN, AY STROBER, W LENARDO, MJ PUCK, JM TI DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME SO CELL LA English DT Article ID MATURE T-CELLS; TUMOR-NECROSIS-FACTOR; CLONAL ELIMINATION; MONOCLONAL-ANTIBODY; RECEPTOR; ANTIGEN; MICE; TOLERANCE; ACTIVATION; DEATH AB Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3(+)CD4(-)CD8(-) lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte apoptosis. Each child had defective Fas-mediated T lymphocyte apoptosis associated with a unique, deleterious Fas gene mutation. One mutation appeared to cause a simple loss of function; however, four others had a dominant negative phenotype when coexpressed with normal Fas. Family studies demonstrated the inheritance of the mutant Fas alleles. The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance. C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 56 TC 1105 Z9 1125 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 16 PY 1995 VL 81 IS 6 BP 935 EP 946 DI 10.1016/0092-8674(95)90013-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RD768 UT WOS:A1995RD76800014 PM 7540117 ER PT J AU ITOH, K ADELSTEIN, RS AF ITOH, K ADELSTEIN, RS TI NEURONAL CELL EXPRESSION OF INSERTED ISOFORMS OF VERTEBRATE NONMUSCLE MYOSIN HEAVY-CHAIN II-B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN RETINOBLASTOMA CELLS; SMOOTH-MUSCLE MYOSIN; DIFFERENTIAL EXPRESSION; SODIUM-BUTYRATE; MESSENGER-RNAS; NERVOUS-SYSTEM; CYCLIC-AMP; CDNA; CLONING; ACID AB Previous work has demonstrated that unique isoforms of nonmuscle myosin heavy chain II-B (MHC-B) are expressed in chicken and human neuronal cells (Takahashi, M., Kawamoto, S., and Adelstein, R. S. (1992) J. Biol. Chem. 267, 17864-17871). These isoforms, which appear to be generated by alternative splicing of pre-mRNA, differ from the MHC-B isoform present in a large number of nonmuscle cells in that they contain inserted cassettes of amino acids near the ATP binding region and/or near the actin binding region. The insert near the ATP binding region begins after amino acid 211 and consists of either 10 or 16 amino acids. The insert nc ar the actin binding region begins after amino acid 621 and consists of 21 amino acids. Using a variety of techniques, we have studied the distribution and expression of the inserted MHC-B isoforms. In the developing chick;en brain, mRNA encoding the 10-amino acid insert gradually increases after embryonic day 4, peaks in the 10-14-day embryo, and then declines. In contrast, the mRNA encoding the 21-amino acid insert appears just before birth and is abundantly expressed in the adult chicken cerebellum. There is a marked species difference between the distribution of the inserted isoforms in adult tissues. The mRNA encoding MHC-B containing the 10-amino acid insert near the ATP binding region is expressed at low levels in the adult chicken brain, but makes up most of the MHC-B mRNA expressed in the human cerebrum and approximately 90% of MHC-B in the human retina. It is also expressed in neuronal cell lines. The mRNA encoding MHC-B containing the 21-amino acid insert is abundantly expressed in the chicken cerebellum and human cerebrum, but is absent from the retina and cell lines, Employing human retinoblastoma (Y-79) and neuroblastoma (SK-N-SH) cell lines, an increase in expression of mRNA encoding the 10-amino acid inserted isoform was seen following treatment by a number of agonists or by serum deprivation. In each case, expression of the inserted MHC-B isoform correlated with cell differentiation (neuronal phenotype) and inhibition of cell division. Using a rat pheochromocytoma cell line (PC12), we found that prior to treatment with nerve growth factor (NGF), there was no evidence for either inserted isoform, although noninserted MHC-B was present. NGF treatment resulted in the appearance of mRNA encoding MHC-B containing the 10-amino acid insert, concomitant with neurite outgrowth. Both the inserted isoform and neurites disappeared following withdrawal of NGF, showing that the appearance and disappearance of the neurites is coupled to the inclusion and exclusion of this MHC-B insert. C1 NHLBI, MOLEC CARDIOL LAB, BETHESDA, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 47 TC 67 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 16 PY 1995 VL 270 IS 24 BP 14533 EP 14540 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500047 PM 7782316 ER PT J AU BERNINSONE, P LIN, ZY KEMPNER, E HIRSCHBERG, CB AF BERNINSONE, P LIN, ZY KEMPNER, E HIRSCHBERG, CB TI REGULATION OF YEAST GOLGI GLYCOSYLATION - GUANOSINE DIPHOSPHATASE FUNCTIONS AS A HOMODIMER IN THE MEMBRANE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RADIATION-INACTIVATION; SACCHAROMYCES-CEREVISIAE; TARGET ANALYSIS; VESICLES; PURIFICATION; INSITU; SIZE AB The Golgi Iumenal GDPase plays an important role in the mannosylation of proteins and Lipids of Saccharomyces cerevisiae by regulating the amount of GDP-mannose available in the Golgi lumen. The enzyme makes available GRIP as an antiporter to be coupled with entry of GDP-mannose into the Golgi lumen from the cytosol. Using radiation inactivation and target analysis, we have now determined the functional molecular mass of the GDPase within the GoIgi membrane and whether or not the enzyme has functional associations with other Golgi membrane proteins, including mannosyltransferases and the GDP-mannose transporter. The functional size of the GDPase was found to be approximately twice the estimated structural target size of the protein; this strongly suggests that the GDPase protein in situ functions as homodimer and does not require association with other membrane proteins for its function. C1 UNIV MASSACHUSETTS, MED CTR, DEPT BIOCHEM & MOLEC BIOL, WORCESTER, MA 01655 USA. NIAMS, PHYS BIOL LAB, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM 30365] NR 20 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 16 PY 1995 VL 270 IS 24 BP 14564 EP 14567 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500051 PM 7540172 ER PT J AU BELAAOUAJ, A SHIPLEY, JM KOBAYASHI, DK ZIMONJIC, DB POPESCU, N SILVERMAN, GA SHAPIRO, SD AF BELAAOUAJ, A SHIPLEY, JM KOBAYASHI, DK ZIMONJIC, DB POPESCU, N SILVERMAN, GA SHAPIRO, SD TI HUMAN MACROPHAGE METALLOELASTASE - GENOMIC ORGANIZATION, CHROMOSOMAL LOCATION, GENE LINKAGE, AND TISSUE-SPECIFIC EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METALLOPROTEINASE INHIBITOR; MATRIX METALLOPROTEINASES; INSITU HYBRIDIZATION; COLLAGENASE GENE; DNA-MOLECULES; LOCALIZATION; RNA; ELASTASE; CLONING AB Human macrophage metalloelastase (HME) is a recent addition to the matrix metalloproteinase (MMP) family that was initially found to be expressed in alveolar macrophages of cigarette smokers. To understand more about HME expression, analysis of the structure and location of the gene was performed. The gene for HME is composed of 10 exons and 9 introns, similar to the stromelysins and collagenases, and HME shares the highly conserved exon size and intron-exon borders with other MMPs. The 13-kilobase (kb) HME gene has been localized by fluorescence in situ hybridization to chromosome 11q22.2-22.3, the same location of the interstitial collagenase and stromelysin genes. We determined that HME and stromelysin 1 genes are physically linked within 62 kb utilizing pulse field gel electrophoresis. The promoter region of the HME gene contains several features common to other MMP genes including a TATA box 29 bp upstream to the transcription initiation site, an AP-1 motif, and a PEA3 element. HME mRNA is not detectable in normal adult tissues but is induced in rapidly remodeling tissues such as the term placenta. In situ hybridization and immunohistochemistry of placental tissue demonstrated HME mRNA and protein expression in macrophages and stromal cells. Cell-specific expression and response to inflammatory stimuli such as endotoxin is conferred within 2.8 kb of the HME 5'-flanking sequence as demonstrated by HME promoter-CAT expression constructs. Knowledge of the genomic organization and chromosomal location of HME may allow us to further define mechanisms responsible for cell- and tissue-specific expression of HME. C1 WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT MED,DIV RESP & CRIT CARE,ST LOUIS,MO 63110. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NCI,DIV CANC ETIOL,BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL2401, P0-1 HL29594] NR 36 TC 123 Z9 127 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 JUN 16 PY 1995 VL 270 IS 24 BP 14568 EP 14575 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500052 PM 7782320 ER PT J AU KAZANIETZ, MG BARCHI, JJ OMICHINSKI, JG BLUMBERG, PM AF KAZANIETZ, MG BARCHI, JJ OMICHINSKI, JG BLUMBERG, PM TI LOW-AFFINITY FINDING OF PHORBOL ESTERS TO PROTEIN-KINASE-C AND ITS RECOMBINANT CYSTEINE-RICH REGION IN THE ABSENCE OF PHOSPHOLIPIDS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 12,13-DIBUTYRATE BINDING; CAENORHABDITIS-ELEGANS; REGULATORY DOMAIN; UNC-13 GENE; ACTIVATION; RECEPTOR; BRAIN; PHOSPHATIDYLSERINE; SEQUENCE; PRODUCT AB Binding of phorbol esters to protein kinase C (PKC) has been regarded as dependent on phospholipids, with phosphatidylserine being the most effective for reconstituting binding. By using a purified single cysteine-rich region from PKC delta expressed in Escherichia coli we were able to demonstrate that specific binding of [H-3]phorbol 12,13-dibutyrate to the receptor still takes place in the absence of the phospholipid cofactor. However, [H-3]phorbol 12,13-dibutyrate bound to the cysteine rich region with 80-fold lower affinity in the absence than in the presence of 100 mu g/ml phosphatidlylserine. Similar results were observed with the intact recombinant PRC delta isolated from insect cells. When different phorbol derivatives were examined, distinct structure-activity relations for the cysteine-rich region were found in the presence and absence of phospholipid. Our results have potential implications for PKC translocation, for inhibitor design, and for PKC structural determination. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 27 TC 66 Z9 66 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 JUN 16 PY 1995 VL 270 IS 24 BP 14679 EP 14684 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500067 PM 7782331 ER PT J AU CABISCOL, E LEVINE, RL AF CABISCOL, E LEVINE, RL TI CARBONIC ANHYDRASE-III - OXIDATIVE MODIFICATION IN-VIVO AND LOSS OF PHOSPHATASE-ACTIVITY DURING AGING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID OXIDATION; S-THIOLATION; GLUTAMINE-SYNTHETASE; PROTEIN OXIDATION; HYDROGEN-PEROXIDE; RAT-LIVER; ISCHEMIA-REPERFUSION; CATALYZED OXIDATION; OXIDIZED PROTEINS; CREATINE-KINASE AB Oxidative modification of DNA, lipids, and proteins occurs as a consequence of reaction with free radicals and activated oxygen. Oxidative modification of total cellular proteins has been described under many pathologic and experimental conditions, but no specific proteins have been identified as in vivo targets for oxidative modification. Utilizing an immunochemical method for detection of oxidatively modified proteins, we identified a protein in rat Liver that was highly oxidized. It was purified to homogeneity and identified as carbonic anhydrase, isozyme III. Its characteristics match those previously described for a protein that was lost during aging of the rat, senescence marker protein-1. Carbonic anhydrase III was purified from rats aged 2, 10, and 18 months, and the proteins were characterized. All three preparations were highly oxidatively modified as assessed by their carbonyl content. The enzyme has three known catalytic activities, and the specific activities for carbon dioxide hydration and for ester hydrolysis decreased during aging by similar to 30%. However, the third activity, that of a phosphatase, was virtually lost during aging. While the physiologic role of carbonic anhydrase III is unknown, we suggest that it functions in an oxidizing environment, which leads to its own oxidative modification. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Cabiscol, Elisa/A-4584-2009; Levine, Rodney/D-9885-2011 OI Cabiscol, Elisa/0000-0003-2795-7999; NR 63 TC 117 Z9 119 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 JUN 16 PY 1995 VL 270 IS 24 BP 14742 EP 14747 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500076 PM 7782339 ER PT J AU RANDAZZO, PA TERUI, T STURCH, S FALES, HM FERRIGE, AG KAHN, RA AF RANDAZZO, PA TERUI, T STURCH, S FALES, HM FERRIGE, AG KAHN, RA TI THE MYRISTOYLATED AMINO-TERMINUS OF ADP-RIBOSYLATION FACTOR-1 IS A PHOSPHOLIPID-SENSITIVE AND GTP-SENSITIVE SWITCH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN N-MYRISTOYLTRANSFERASE; ADENYLATE-CYCLASE; BINDING PROTEINS; GOLGI MEMBRANES; SACCHAROMYCES-CEREVISIAE; REGULATORY COMPONENT; NUCLEOTIDE-BINDING; RNA-POLYMERASE; CHOLERA-TOXIN; CLONED GENES AB ADP-ribosylation factor 1 (Arf1) is an essential N-myristoylated 21-kDa GTP-binding protein with activities that include the regulation of membrane traffic and phospholipase D activity. Both the N terminus of the protein and the N-myristate bound to glycine 2 have previously been shown to be essential to the function of Arf in cells. We show that the bound nucleotide affects the conformation of either the N terminus or residues of Arf1 that are in direct contact with the N terminus. This was demonstrated by examining the effects of mutations in this N-terminal domain on guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) and GDP binding and dissociation kinetics. Arf1 mutants, lacking 13 or 17 residues from the N terminus or mutated at residues 3-7, had a greater affinity for GTP gamma S and a lower affinity for GDP than did the wild-type protein. As the N terminus is required for interactions with target proteins, we conclude that the N terminus of Arf1 is a GTP-sensitive effector domain. When Arf1 was acylated, the GTP-dependent conformational changes were codependent on added phospholipids. In the absence of phospholipids, myristoylated Arf1 has a lower affinity for GTP gamma S than for GDP, and in the presence of phospholipids, the myristoylated protein has a greater affinity for GTP gamma S than for GDP. Thus, N-myristoylation is a critical component in the construction of this phospholipid- and GTP-dependent switch. C1 MAXENT SOLUT LTD, CAMBRIDGE CB75 QS1, ENGLAND. RP RANDAZZO, PA (reprint author), NCI, DIV CANC TREATMENT,DEV THERAPEUT PROGRAM, BIOL CHEM LAB,BLDG 37, RM 5D-02, BETHESDA, MD 20892 USA. NR 49 TC 81 Z9 82 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 16 PY 1995 VL 270 IS 24 BP 14809 EP 14815 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500085 PM 7782347 ER PT J AU BOUJRAD, N OGWUEGBU, SO GARNIER, M LEE, CH MARTIN, BM PAPADOPOULOS, V AF BOUJRAD, N OGWUEGBU, SO GARNIER, M LEE, CH MARTIN, BM PAPADOPOULOS, V TI IDENTIFICATION OF A STIMULATOR OF STEROID-HORMONE SYNTHESIS ISOLATED FROM TESTIS SO SCIENCE LA English DT Article ID LEYDIG-CELL STEROIDOGENESIS; RAT SERTOLI CELLS; TISSUE INHIBITOR; SEMINIFEROUS TUBULES; MATRIX METALLOPROTEINASES; TESTICULAR FUNCTION; GRANULOSA-CELLS; INVITRO; PROTEIN; PURIFICATION AB Gonadal steroidogenesis is regulated by pituitary gonadotropins and a locally produced, unidentified factor. A 70-kilodalton (kD) protein complex secreted from rat Serloli cells was isolated. The complex, composed of 28- and 38-kD proteins, stimulated steroidogenesis by Leydig cells and ovarian granulosa cells in a dose-dependent and adenosine 3',5'-monophosphate-independent manner. The follicle-stimulating hormone-induced 28-kD protein appeared to be responsible for the bioactivity, but the 38-kD protein was indispensable for maximal activity. The 28- and 38-kD proteins were shown to be identical to the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the proenzyme form of cathepsin L, respectively. Thus, a TIMP-1-procathepsin L complex is a potent activator of steroidogenesis and may regulate steroid concentrations and, thus, germ cell development in both males and females. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. RI BOUJRAD, Noureddine /L-1367-2015; OI Papadopoulos, Vassilios/0000-0002-1183-8568 FU NICHD NIH HHS [HD01031, HD24633] NR 50 TC 137 Z9 147 U1 0 U2 2 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 16 PY 1995 VL 268 IS 5217 BP 1609 EP 1612 DI 10.1126/science.7777858 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RD459 UT WOS:A1995RD45900035 PM 7777858 ER PT J AU ANDERSON, JL GREENBERG, B BODEN, W KRAUSESTEINRAUF, H BRISTOW, MR ZELIS, R CARSON, P LAVORI, PW COLLING, C LINDENFELD, J DOMANSKI, MJ DEYKIN, D EICHHORN, EJ AF ANDERSON, JL GREENBERG, B BODEN, W KRAUSESTEINRAUF, H BRISTOW, MR ZELIS, R CARSON, P LAVORI, PW COLLING, C LINDENFELD, J DOMANSKI, MJ DEYKIN, D EICHHORN, EJ TI DESIGN OF THE BETA-BLOCKER EVALUATION SURVIVAL TRIAL (BEST) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; IDIOPATHIC DILATED CARDIOMYOPATHY; HUMAN VENTRICULAR MYOCARDIUM; ADRENERGIC-BLOCKADE; DOUBLE-BLIND; BUCINDOLOL; METOPROLOL; TERM; WITHDRAWAL; INFARCTION AB Central to our current understanding of heart failure is the concept that compensatory mechanisms that maintain blood pressure and perfusion ultimately contribute to worsening of ventricular function. Studies of the effect of angiotensin-converting enzyme inhibitors in patients with heart failure are consistent with this paradigm. This manuscript describes a 2,800-patient randomized trial that will definitively determine whether sympathetic nervous system antagonism with a beta blocker prolongs the life of patients with moderate to severe heart failure. C1 NHLBI,BETHESDA,MD 20892. RI bristow, michael/G-7850-2011 NR 29 TC 85 Z9 85 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1995 VL 75 IS 17 BP 1220 EP 1223 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RD135 UT WOS:A1995RD13500007 ER PT J AU GUETTA, V PANZA, JA WACLAWIW, MA CANNON, RO AF GUETTA, V PANZA, JA WACLAWIW, MA CANNON, RO TI EFFECT OF COMBINED 17-BETA-ESTRADIOL AND VITAMIN-E ON LOW-DENSITY-LIPOPROTEIN OXIDATION IN POSTMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID DISEASE RP GUETTA, V (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 7 TC 26 Z9 28 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1995 VL 75 IS 17 BP 1274 EP 1276 DI 10.1016/S0002-9149(99)80780-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RD135 UT WOS:A1995RD13500021 PM 7778557 ER PT J AU WHELAN, EA SANDLER, DP WEINBERG, CR AF WHELAN, EA SANDLER, DP WEINBERG, CR TI MENSTRUAL-CYCLE PATTERNS AND RISK OF BREAST-CANCER - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP WHELAN, EA (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1995 VL 141 IS 12 BP 1201 EP 1201 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RB996 UT WOS:A1995RB99600013 ER PT J AU MINOR, JR AF MINOR, JR TI INTERLEUKIN-2 IN HIV-INFECTION SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter RP MINOR, JR (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 15 PY 1995 VL 52 IS 12 BP 1345 EP 1346 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RC741 UT WOS:A1995RC74100013 PM 7656123 ER PT J AU BOUMPAS, DT AUSTIN, HA FESSLER, BJ BALOW, JE KLIPPEL, JH LOCKSHIN, MD AF BOUMPAS, DT AUSTIN, HA FESSLER, BJ BALOW, JE KLIPPEL, JH LOCKSHIN, MD TI SYSTEMIC LUPUS-ERYTHEMATOSUS - EMERGING CONCEPTS .1. RENAL, NEUROPSYCHIATRIC, CARDIOVASCULAR, PULMONARY, AND HEMATOLOGIC DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID IMMUNE THROMBOCYTOPENIC PURPURA; ACUTE NONLYMPHOCYTIC LEUKEMIA; RIBOSOMAL-P-PROTEINS; ANTI-DNA ANTIBODIES; ANTIPHOSPHOLIPID ANTIBODIES; PULSE CYCLOPHOSPHAMIDE; LONG-TERM; INTRAVENOUS CYCLOPHOSPHAMIDE; CARDIAC ABNORMALITIES; TRANSVERSE MYELITIS AB Purpose: To review advances and controversies in the diagnosis and management of systemic lupus erythematosus with visceral involvement (renal, neuropsychiatric, cardiopulmonary, and hematologic disease). Data Sources and Study Selection: Review of the English-language medical literature with emphasis on articles published in the last 5 years. More than 400 articles were reviewed. Data Synthesis: Recent debates pertaining to lupus nephritis have focused on the value of kidney biopsy data and the role of cytotoxic drug therapies. Many studies have shown that estimates of prognosis are enhanced by consideration of clinical, demographic, and histologic features. For patients with severe lupus nephritis, an extended course of pulse cyclophosphamide therapy is more effective than a 6-month course of pulse methylprednisolone therapy in preserving renal function. Adding a quarterly maintenance regimen to monthly pulse cyclophosphamide therapy reduces the rate of exacerbations. Plasmapheresis appears not to enhance the effectiveness of prednisone and daily oral cyclophosphamide. Small case series have shown pulses of cyclophosphamide to be beneficial in patients with lupus and neuropsychiatric disease refractory to glucocorticoid therapy, acute pulmonary disease (pneumonitis or hemorrhage), and thrombocytopenia. Patients with systemic lupus erythematosus have an increased prevalence of valvular and atherosclerotic heart disease, apparently because of factors related to the disease itself and to drug therapy. Conclusions: Cytotoxic agents are superior to glucocorticoid therapy for the treatment of proliferative lupus nephritis, but the optimal duration and intensity of cytotoxic therapy remain undefined. Definitive studies of the treatment of autoimmune thrombocytopenia and acute pulmonary disease and of the diagnosis and treatment of neuropsychiatric disease are not available. RP BOUMPAS, DT (reprint author), NIH,BLDG 10,ROOM 3N-112,BETHESDA,MD 20892, USA. NR 124 TC 224 Z9 226 U1 2 U2 3 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 JUN 15 PY 1995 VL 122 IS 12 BP 940 EP 950 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA RC270 UT WOS:A1995RC27000009 PM 7755231 ER PT J AU AVGERINOS, PC CUTLER, GB AF AVGERINOS, PC CUTLER, GB TI THE CUSHING-SYNDROME SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP AVGERINOS, PC (reprint author), NICHHD,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 JUN 15 PY 1995 VL 122 IS 12 BP 959 EP 960 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RC270 UT WOS:A1995RC27000013 PM 7619161 ER PT J AU GENDREAU, S LARDANS, V CADORET, JP MIALHE, E AF GENDREAU, S LARDANS, V CADORET, JP MIALHE, E TI TRANSIENT EXPRESSION OF A LUCIFERASE REPORTER GENE AFTER BALLISTIC INTRODUCTION INTO ARTEMIA-FRANCISCANA (CRUSTACEA) EMBRYOS SO AQUACULTURE LA English DT Article DE TECHNIQUES GENETICS; ARTEMIA FRANCISCANA; LUCIFERASE GENE; PHSP 70 PROMOTER; TRANSIENT EXPRESSION; BALLISTIC GENE TRANSFER AB Using the PDS 1000/He ballistic gene transfer apparatus from BioRad, Artemia franciscana embryos were bombarded with high velocity gold microparticles coated with a circular plasmid containing a luciferase reporter gene placed under the control of the Drosophila melanogaster hsp 70 promoter (3000 to 10000 embryos per shot). Even for the most drastic ballistic parameters investigated on dechorionated cysts (rupture disk, 1800 psi; distance D between the stopping screen and the embryos, 35 mm), no significant luciferase activity was detected after heat shock (30 min, 41 degrees C). After bombarding protruding embryos obtained 20 h after dechorionated cyst rehydration, the best result in terms of embryo survival and luciferase activity was obtained for D = 35 mm with a 450-psi rupture disk. For these parameters, significant luciferase activity was observed 12 and 24 h after bombardment, but not at 48 h. In this particular model, the data suggest transient luciferase expression, with a peak of luciferase activity within the 12 h following bombardment. These results indicate that the ballistic technique is useful for studying transgene promoter efficiency in crustaceans and suggest its utility for attempting the production of transgenic animals. C1 UNIV MONTPELLIER 2,IFREMER,CNRS,UMR 9947,F-34095 MONTPELLIER 05,FRANCE. INST PASTEUR,U167,F-59019 LILLE,FRANCE. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NR 13 TC 28 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD JUN 15 PY 1995 VL 133 IS 3-4 BP 199 EP 205 DI 10.1016/0044-8486(94)00369-Y PG 7 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA RG042 UT WOS:A1995RG04200003 ER PT J AU BRIGHAM, J HERNING, RI MOSS, HB AF BRIGHAM, J HERNING, RI MOSS, HB TI EVENT-RELATED POTENTIALS AND ALPHA-SYNCHRONIZATION IN PREADOLESCENT BOYS AT RISK FOR PSYCHOACTIVE SUBSTANCE USE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SUBSTANCE ABUSE; RISK FACTORS; ALCOHOLISM; AUDITORY EVENT-RELATED POTENTIALS; HERITABILITY; EVENT-RELATED SYNCHRONIZATION ID ATTENTION-DEFICIT DISORDER; BRAIN POTENTIALS; HYPERACTIVITY DISORDER; PSYCHIATRIC-DIAGNOSIS; EVOKED-RESPONSE; MEMORY SPAN; ALCOHOLISM; EEG; CHILDREN; P300 AB Numerous studies have evaluated event-related potentials (ERPs) as biological indicators of the liability for alcoholism. This study extends that approach by investigating ERPs in boys at risk for other substance use disorders. Prepubertal (10-12 years) sons of fathers diagnosed with psychoactive substance dependence (n = 28) were compared to matched sons of nonaffected fathers (n = 26) on an auditory ERP oddball task. Multivariate analyses of variance applied to peak amplitude and latency measures indicated small to moderate between-groups differences at midline or parietal sites: N2 and P3 amplitude; P2, N2, P3, and Nc latency. This replicated P3 amplitude findings in alcoholism-risk studies, though the effect size was moderate. Analysis of event-related alpha power indicated significantly longer latency of alpha synchronization and oscillations of desynchronization in boys at risk. The alpha power findings were statistically the more robust of the measures applied. The role of neurocognitive factors in determining liability for substance use disorders is discussed. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD. RP BRIGHAM, J (reprint author), UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,CTR EDUC & DRUG ABUSE RES,PITTSBURGH,PA 15213, USA. FU NIAAA NIH HHS [AA 07453-12]; NIDA NIH HHS [P50-DA 05605] NR 65 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD JUN 15 PY 1995 VL 37 IS 12 BP 834 EP 846 DI 10.1016/0006-3223(94)00218-R PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RH701 UT WOS:A1995RH70100002 PM 7548458 ER PT J AU YOUNG, NS BARRETT, AJ AF YOUNG, NS BARRETT, AJ TI THE TREATMENT OF SEVERE ACQUIRED APLASTIC-ANEMIA SO BLOOD LA English DT Review ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; VERSUS-HOST DISEASE; SAA-WORKING-PARTY; TERM FOLLOW-UP; HLA-IDENTICAL SIBLINGS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; PROSPECTIVE RANDOMIZED TRIAL; HIGH-DOSE METHYLPREDNISOLONE; ANTITHYMOCYTE GLOBULIN ATG RP YOUNG, NS (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 123 TC 145 Z9 153 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 JUN 15 PY 1995 VL 85 IS 12 BP 3367 EP 3377 PG 11 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800001 PM 7780125 ER PT J AU MASOOD, R ZHANG, Y BOND, MW SCADDEN, DT MOUDGIL, T LAW, RE KAPLAN, MH JUNG, B ESPINA, BM LUNARDIISKANDAR, Y LEVINE, AM GILL, PS AF MASOOD, R ZHANG, Y BOND, MW SCADDEN, DT MOUDGIL, T LAW, RE KAPLAN, MH JUNG, B ESPINA, BM LUNARDIISKANDAR, Y LEVINE, AM GILL, PS TI INTERLEUKIN-10 IS AN AUTOCRINE GROWTH-FACTOR FOR ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED B-CELL LYMPHOMA SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; EXPRESSION; AIDS; INDUCTION; ANTIBODY; HOMOLOGY; IL-10; BCRFI AB Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombi- nant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis. (C) 1995 by The American Society of Hematology. C1 UNIV SO CALIF,NORRIS CANC HOSP & RES INST,NORRIS CANC CTR,DEPT MED,LOS ANGELES,CA 90033. DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. HARVARD UNIV,DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. CORNELL UNIV,N SHORE UNIV HOSP,COLL MED,DON MONTI DIV ONCOL,MANHASSET,NY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA5162, CA55510]; NHLBI NIH HHS [HL 48499] NR 28 TC 132 Z9 133 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 JUN 15 PY 1995 VL 85 IS 12 BP 3423 EP 3430 PG 8 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800006 PM 7780129 ER PT J AU TORTOLANI, PJ JOHNSTON, JA BACON, CM MCVICAR, DW SHIMOSAKA, A LINNEKIN, D LONGO, DL OSHEA, JJ AF TORTOLANI, PJ JOHNSTON, JA BACON, CM MCVICAR, DW SHIMOSAKA, A LINNEKIN, D LONGO, DL OSHEA, JJ TI THROMBOPOIETIN INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF THE JANUS KINASE, JAK2 SO BLOOD LA English DT Article ID FACTOR RECEPTOR SUPERFAMILY; GAMMA SIGNAL-TRANSDUCTION; INTERFERON-ALPHA/BETA; MOLECULAR-CLONING; CELL-LINE; C-MPL; MEMBER; GROWTH; ERYTHROPOIETIN; PROTOONCOGENE AB Thrombopoietin (TPO) is a recently characterized growth and differentiation factor for megakaryocytes and platelets that exerts its effects via the receptor, c-Mpl. This receptor is a member of the hematopoietin receptor superfamily and is essential for megakaryocyte maturation; however, the molecular mechanisms of TPO and c-Mpl action have not been elucidated. Recently, the Janus kinases have emerged as important elements in signaling via this family of receptors. In this report, we show that, in the M07e megakaryocytic cell line, which expresses c-Mpl and proliferates in response to TPO, TPO induces phosphorylation of a number of substrates between 80 and 140 kD. Specifically, we show that stimulation with TPO induces the rapid tyrosine phosphorylation of a 130-kD protein that we identity as the Janus kinase, JAK2. However, no detectable tyrosine phosphorylation of JAK1, JAK3, or TYK2 was observed. TPO also induced activation of JAK2 phosphotransferase activity in vitro. Taken together, these data indicate that JAK2 likely plays a key role in TPO-mediated signal transduction. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD,S YORKSHIRE,ENGLAND. KIRIN BREWING LTD,TOKYO,JAPAN. RP TORTOLANI, PJ (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BLDG 10,ROOM 9N-262,10 CTR DR,BETHESDA,MD 20892, USA. RI McVicar, Daniel/G-1970-2015 NR 33 TC 80 Z9 81 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1995 VL 85 IS 12 BP 3444 EP 3451 PG 8 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800009 PM 7780132 ER PT J AU SAUSVILLE, EA HEADLEE, D STETLERSTEVENSON, M JAFFE, ES SOLOMON, D FIGG, WD HERDT, J KOPP, WC RAGER, H STEINBERG, SM GHETIE, V SCHINDLER, J UHR, J WITTES, RE VITETTA, ES AF SAUSVILLE, EA HEADLEE, D STETLERSTEVENSON, M JAFFE, ES SOLOMON, D FIGG, WD HERDT, J KOPP, WC RAGER, H STEINBERG, SM GHETIE, V SCHINDLER, J UHR, J WITTES, RE VITETTA, ES TI CONTINUOUS-INFUSION OF THE ANTI-CD22 IMMUNOTOXIN IGG-RFB4-SMPT-DGA IN PATIENTS WITH B-CELL LYMPHOMA - A PHASE-I STUDY SO BLOOD LA English DT Article ID RICIN-A-CHAIN; ANTI-B4-BLOCKED RICIN; RECEPTOR; THERAPY; ANTIBODY; INTERLEUKIN-2; NEOPLASMS; TRIAL; CD22 AB IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupled to the monoclonal antihuman CD22 antibody, RFB4. This study determined the maximally tolerated dose (MTD) of this immunotoxin (IT) administered as a continuous 8-day infusion to 18 patients with B-cell lymphoma (30% CD22(+) tumor cells) over 8 days. The MTD was 19.2 mg/m(2)/192 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as dose-limiting toxicity (DLT) at 28.8 mg/m(2)/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT concentrations greater than 1,000 ng/mL and the absence of circulating tumor cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial responses, 3 minor responses, 6 stable disease, and 3 progression of disease were observed. The mean maximal serum concentration (C-max) in initial courses at the MTD (19.2 mg/m(2)) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m(2)/192 h, the C-max was highly variable (n =11 mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human antimouse or antiricin antibodies developed in 6 of 16 (37.5%) patients after one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did not correlate with toxicity but decreased soluble interleukin-2 receptor concentrations correlated with clinical response. Comparison to a prior study with the same It administered by intermittent bolus infusions (Amlot et al, Blood 82:2624, 1993) suggests similar clinical response, toxicity, and immunogenicity. This is a US government work. There are no restrictions on its use. C1 NCI,BIOL CHEM LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. PRI DYNCORP,FREDERICK,MD. UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [CA-28149] NR 29 TC 153 Z9 155 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1995 VL 85 IS 12 BP 3457 EP 3465 PG 9 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800011 PM 7780133 ER PT J AU MOSSALAYI, MD MENTZ, F OUAAZ, F DALLOUL, AH BLANC, C DEBRE, P RUSCETTI, FW AF MOSSALAYI, MD MENTZ, F OUAAZ, F DALLOUL, AH BLANC, C DEBRE, P RUSCETTI, FW TI EARLY HUMAN THYMOCYTE PROLIFERATION IS REGULATED BY AN EXTERNALLY CONTROLLED AUTOCRINE TRANSFORMING GROWTH-FACTOR-BETA-1 MECHANISM SO BLOOD LA English DT Article ID T-CELL PRECURSORS; HUMAN LYMPHOCYTES-T; FACTOR-BETA; TGF-BETA; ACTIVATION; INHIBITION; DIFFERENTIATION; PATHWAY; PHOSPHORYLATION; INTERLEUKIN-1 AB Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2(+)CD3/TCR(-)CD4(-)CD8(-) (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2(I+III)-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL-7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3(+)CD8(+)CD4(-) cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8(+) cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8(+) cell-derived inhibition of TN cell growth. Analysis of CD8(+) cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8(+) cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output. (C) 1995 by The American Society of Hematology. C1 NCI,LEUKOCYTE BIOL LAB,FREDERICK,MD 21701. RP MOSSALAYI, MD (reprint author), HOP LA PITIE SALPETRIERE,CNRS,URA 625,MOLEC IMMUNOHEMATOL GRP,91 BD HOP,F-75013 PARIS,FRANCE. NR 57 TC 22 Z9 24 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 JUN 15 PY 1995 VL 85 IS 12 BP 3594 EP 3601 PG 8 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800027 PM 7780143 ER PT J AU BRISTOL, LA BACHOVCHIN, W TAKACS, L AF BRISTOL, LA BACHOVCHIN, W TAKACS, L TI INHIBITION OF CD26 ENZYME-ACTIVITY WITH PRO-BOROPRO STIMULATES RAT GRANULOCYTE-MACROPHAGE COLONY FORMATION AND THYMOCYTE PROLIFERATION IN-VITRO SO BLOOD LA English DT Article ID DIPEPTIDYL PEPTIDASE-IV; T-CELL ACTIVATION; HUMAN LYMPHOCYTE-T; MONOCLONAL-ANTIBODY; COSTIMULATING ANTIGEN; NEUTRAL ENDOPEPTIDASE; MOLECULAR-CLONING; AMINOPEPTIDASE; BESTATIN; DIFFERENTIATION AB CD26 dipeptidyl peptidase (DPPIV) is involved in the regulation of proliferation of some hematopoietic and T-lineage cells. Here, we show that Pro-boropro a potent inhibitor of DPP activity has a costimulating effect in hematopoietic colony assays for macrophage and, to a lesser extent, for granulocyte colonies and has a stimulating effect in organ cultures of immature thymocytes. Based on these and other evidences, we propose that the mechanism by which CD26 regulates proliferation is associated with its DPP activity. (C) 1995 by The American Society of Hematology. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,SPECIAL PROJECTS UNIT,ROCKVILLE,MD 20852. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. NR 49 TC 9 Z9 9 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 JUN 15 PY 1995 VL 85 IS 12 BP 3602 EP 3609 PG 8 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800028 PM 7780144 ER PT J AU SHURTLEFF, SA MEYERS, S HIEBERT, SW RAIMONDI, SC HEAD, DR WILLMAN, CL WOLMAN, S SLOVAK, ML CARROLL, AJ BEHM, F HULSHOF, MG MOTRONI, TA OKUDA, T LIU, P COLLINS, FS DOWNING, JR AF SHURTLEFF, SA MEYERS, S HIEBERT, SW RAIMONDI, SC HEAD, DR WILLMAN, CL WOLMAN, S SLOVAK, ML CARROLL, AJ BEHM, F HULSHOF, MG MOTRONI, TA OKUDA, T LIU, P COLLINS, FS DOWNING, JR TI HETEROGENEITY IN CBF-BETA/MYH11 FUSION MESSAGES ENCODED BY THE INV(16)(P13Q22) AND THE T(16-16)(P13-Q22) IN ACUTE MYELOGENOUS LEUKEMIA SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; DNA-BINDING; GENE; RUNT; IDENTIFICATION; CHROMOSOME-16; AML1; TRANSLOCATION AB Inv(16)(p13q22) is one of the most frequent chromosomal rearrangements found in acute myelogenous leukemia (AML), representing approximately 16% of documented karyotypic abnormalities. The inv(16) breakpoints have been cloned and shown to involve the non-DNA binding component of the AML-1 transcription factor complex termed core binding factor beta gene (CBF beta) on 16q and the smooth muscle myosin heavy chain gene (MYH11) on 16p. In this study, we analyzed 37 cases of inv(16)-containing AML and 4 cases with t(16;16)(p13;q22) for expression of the CBF beta/MYH11 chimeric message by reverse transcription-polymerase chain reaction (PCR) analysis. CBF beta/MYH11 chimeric messages were detected in 33 of 37 cases with the inv(16) and in the 4 t(16;16)-containing cases. Sequence analysis of PCR products showed extensive breakpoint heterogeneity in both CBF beta and MYH11. In addition to the previously described breakpoint in CBF beta at nucleotide (nt) 495 (amino acid 165), we have identified a second novel fusion point at nt 399 (amino acid 133) in 7% of the cases. Similarly, a unique breakpoint site was identified in MYH11 at nt 1098, as well as at three previously characterized sites at nts 994, 1201, and 1921. Of the 4 PCR-negative cases, 2 of 3 tested lacked CBF beta rearrangements by Southern blot analysis, suggesting the possible involvement of a different genomic locus in some cases with cytogenetic evidence of inv(16). To assess whether the portions of CBF beta contained within the CBF beta/MYH11 chimeric products retain the ability to interact with their heterodimeric DNA-binding partner AML-1, we performed in vitro DNA-binding analysis. Recombinant CBF beta polypeptides consisting of the N-terminal 165 amino acids retained their ability to interact with AML-1, whereas mutants containing only the N-terminal 133 amino acids interacted with AML-1 less efficiently. These data suggest that different CBF beta/MYH11 products may vary subtly in their biologic activities. (C) 1995 by The American Society of Hematology. C1 ST JUDE CHILDRENS RES HOSP, DEPT PATHOL, MEMPHIS, TN 38105 USA. ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA. UNIV NEW MEXICO, SCH MED, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. ONCOR INC, GAITHERSBURG, MD USA. CITY HOPE NATL MED CTR, DUARTE, CA 91010 USA. UNIV ALABAMA, MED GENET LAB, BIRMINGHAM, AL 35294 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. PEDIAT ONCOL GRP, CHICAGO, IL USA. SW ONCOL GRP, SAN ANTONIO, TX USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA-01429, CA-32102, CA-64140] NR 25 TC 91 Z9 94 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1995 VL 85 IS 12 BP 3695 EP 3703 PG 9 WC Hematology SC Hematology GA RD288 UT WOS:A1995RD28800038 PM 7780153 ER PT J AU THIBAULT, A SAMID, D COOPER, MR FIGG, WD TOMPKINS, AC PATRONAS, N HEADLEE, DJ KOHLER, DR VENZON, DJ MYERS, CE AF THIBAULT, A SAMID, D COOPER, MR FIGG, WD TOMPKINS, AC PATRONAS, N HEADLEE, DJ KOHLER, DR VENZON, DJ MYERS, CE TI PHASE-I STUDY OF PHENYLACETATE ADMINISTERED TWICE-DAILY TO PATIENTS WITH CANCER SO CANCER LA English DT Article DE PHENYLACETATE; PHARMACOKINETICS; DIFFERENTIATION; GLIOMA; PROSTATE CANCER ID PROSTATE-SPECIFIC ANTIGEN; DIFFERENTIATION; CELLS; PHENYLALANINE; DERIVATIVES; INHIBITION; ENZYMES; BRAIN; ACID AB Background. The growth-inhibiting and differentiating effects of sodium phenylacetate against hematopoietic and solid tumor cell lines has aroused clinical interest in its use as an anticancer drug. In an earlier Phase I trial of phenylacetate aimed at maintaining serum drug concentrations in the range that proved active in vitro (>250 mu g/ml) for 2 consecutive weeks, infusion rates approached the maximum velocity of drug elimination and commonly resulted in drug accumulation and reversible dose-limiting neurologic toxicity. In this study, the authors described the nonlinear pharmacokinetics, metabolism, toxicity, and clinical activity of phenylacetate. Methods. The treatment regimen of this Phase I study was designed to expose patients intermittently to drug concentrations exceeding 250 mu g/ml and to allow time for drug elimination to occur between doses to minimize accumulation. Sodium phenylacetate was administered as a 1-hour infusion twice daily (8 a.m., 5 p.m.) at two dose levels of 125 and 150 mg/kg for a 2-week period. Therapy was repeated at 4-week intervals far patients who did not experience dose-limiting toxicity or disease progression. Results. Eighteen patients (4 of whom previously were treated with phenylacetate by continuous intravenous infusion received 27 cycles of therapy. Detailed pharmacokinetic studies for eight patients indicated that phenylacetate induced its own clearance by a factor of 27% in a 2-week period. Dose-limiting toxicity, consisting of reversible central nervous system depression, was observed for three patients at the second dose level. One patient with refractory malignant glioma had a partial response, and one with hormone-independent prostate cancer achieved a 50% decline in prostate specific antigen level, which was maintained for I month. Conclusions. Phenylacetate administered at a dose of 125 mg/kg twice daily for 2 consecutive weeks is well tolerated. High grade gliomas and advanced prostate cancer are reasonable targets for Phase II clinical trials. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD. RP THIBAULT, A (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12 N 214,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 27 TC 95 Z9 97 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 JUN 15 PY 1995 VL 75 IS 12 BP 2932 EP 2938 DI 10.1002/1097-0142(19950615)75:12<2932::AID-CNCR2820751221>3.0.CO;2-P PG 7 WC Oncology SC Oncology GA RC116 UT WOS:A1995RC11600020 PM 7773944 ER PT J AU WANG, TTY PHANG, JM AF WANG, TTY PHANG, JM TI EFFECTS OF ESTROGEN ON APOPTOTIC PATHWAYS IN HUMAN BREAST-CANCER CELL-LINE MCF-7 SO CANCER RESEARCH LA English DT Note AB We utilized a reverse transcription-PCR method to examine the effect of estrogen on the expression of mRNA for Bcl-2 and Bax, two modulatory proteins in the apoptotic pathway, in human breast cancer cell line MCF-7. We found that the bcl-2 mRNA levels in the cells exposed to 17 beta-estradiol were higher than those of control cells. Although the relative bax mRNA levels remained unchanged, the changes in bcl-2 mRNA level occurred in a time- and concentration-dependent fashion. In addition, pretreatment with 17 beta-estradiol protected MCF-7 cells from apoptosis. Our study provides evidence that responses of breast epithelial cells toward a steroid sex hormone involve regulation of the apoptotic pathway. RP WANG, TTY (reprint author), NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC REGULAT LAB,BLDG 434-2,POB,FREDERICK,MD 21702, USA. NR 12 TC 243 Z9 251 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1995 VL 55 IS 12 BP 2487 EP 2489 PG 3 WC Oncology SC Oncology GA RC936 UT WOS:A1995RC93600001 PM 7780952 ER PT J AU LEVEDAKOU, EN KAUFMANN, WK ALCORTA, DA GALLOWAY, DA PAULES, RS AF LEVEDAKOU, EN KAUFMANN, WK ALCORTA, DA GALLOWAY, DA PAULES, RS TI P21(CIP1) IS NOT REQUIRED FOR THE EARLY G(2) CHECKPOINT RESPONSE TO IONIZING-RADIATION SO CANCER RESEARCH LA English DT Note ID CYCLIN-DEPENDENT KINASES; P53; INHIBITOR; PROTEIN; SUBUNIT; P21 AB We have previously reported that the immediate G(2) checkpoint delay of normal human fibroblasts in response to ionizing radiation is correlated with inhibition of p34(CDC2)/cyclin B kinase activity. Here, we observed increased amounts of the cyclin-dependent protein kinase inhibitor p21(CIP1) associated with p34(CDC2)/cyclin B protein complexes from irradiated normal human fibroblasts. Since wild-type p53 function is not required for the early G(2) checkpoint response to ionizing radiation, we investigated whether a p53-independent induction of p21(CIP1) was required for the G(2) checkpoint. Early passage human fibroblasts expressing the E6 oncoprotein of human papilloma virus-type 16 (NHF4 E6) were analyzed. It has been demonstrated earlier that inactivation of wild-type p53 function in these cells by E6 protein does not alter their intact early G(2) checkpoint response to gamma-rays. p21(CIP1) was found to be undetectable in p34(CDC2)/cyclin B protein complexes and in total extracts from the E6-expressing cells, with or without exposure to ionizing radiation. These data indicate that p21(CIP1) is not required for the immediate G(2) checkpoint response and is not induced by a p53-independent pathway in G(2) phase following exposure to gamma-rays. C1 NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,DEPT PATHOL,CHAPEL HILL,NC 27599. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. FU NCI NIH HHS [P01 CA042765] NR 21 TC 37 Z9 37 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 JUN 15 PY 1995 VL 55 IS 12 BP 2500 EP 2502 PG 3 WC Oncology SC Oncology GA RC936 UT WOS:A1995RC93600005 PM 7780956 ER PT J AU GINSBURG, E VONDERHAAR, BK AF GINSBURG, E VONDERHAAR, BK TI PROLACTIN SYNTHESIS AND SECRETION BY HUMAN BREAST-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID GROWTH-HORMONE; DNA-SYNTHESIS; BIOLOGICAL-ACTIVITY; PORCINE PROLACTIN; EPITHELIAL-CELLS; NONCODING EXON; MESSENGER-RNA; MAMMARY; CULTURE; SERUM AB A possible autocrine function of prolactin (Prl) in human breast cancer was explored by the addition of a panel of anti-human Pd mAbs to T47Dco and MCF7 human breast adenocarcinoma cells. mAb 631 and mAb 390 inhibited cell growth by 86 and 68%, respectively, in the estrogen receptor-negative T47Dco cells and by 20 and 71%, respectively, in the estrogen receptor-positive MCF7 cells. Conditioned medium prepared from T47Dco cells was assessed for the presence of Prl-like molecules by its ability to stimulate growth of Prl-responsive Nb2 rat lymphoma cells. Growth of Nb2 cells under the influence of human Prl or conditioned medium,vas abolished when either solution was pretreated with mAb 390, followed by Immunobead precipitation (Bio-Rad, Melville, NY). T47Dco cells secrete 0.7 mu g lactogen/ml over a 24-48-h period. With the use of reverse transcription-PCR, an expected 612-bp band was detected by ethidium bromide staining, and its similarity to pituitary Prl was confirmed by Southern blot analysis with the use of human Prl cDNA as a probe. A single M(r) 22,000 band, the dominant size of monomeric pituitary Prl, was found in immunoprecipitates of both cell extracts and conditioned medium from T47Dco cells labeled metabolically with [S-35]cysteine. These data suggest that human breast cancer cells synthesize and secrete biologically active Prl. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 46 TC 203 Z9 207 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1995 VL 55 IS 12 BP 2591 EP 2595 PG 5 WC Oncology SC Oncology GA RC936 UT WOS:A1995RC93600022 PM 7780973 ER PT J AU HONGYO, T BUZARD, GS PALLI, D WEGHORST, CM AMOROSI, A GALLI, M CAPORASO, NE FRAUMENI, JF RICE, JM AF HONGYO, T BUZARD, GS PALLI, D WEGHORST, CM AMOROSI, A GALLI, M CAPORASO, NE FRAUMENI, JF RICE, JM TI MUTATIONS OF THE K-RAS AND P53 GENES IN GASTRIC ADENOCARCINOMAS FROM A HIGH-INCIDENCE REGION AROUND FLORENCE, ITALY SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; TUMOR SUPPRESSOR GENE; POINT MUTATIONS; LUNG-CANCER; POLYMORPHISM; CARCINOMA; SPECTRUM; P53-GENE; COMMON; DIET AB K-ras and p53 gene mutations in intestinal-type gastric carcinomas from a high-incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single-strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (including two at a previously unreported site in codon 11), a significantly higher frequency than reported in countries other than Japan. No K-ras mutations were identified in stage III tumors. Single-strand conformation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, with mutations identifiable by direct sequencing in 65% of the eases. Of these, 91% were base substitutions, a value similar to that usually reported, but the percentage of G:C to A:T transitions (90% in this study, 89% in all published European cases combined) differed significantly from that in Oriental cases (48%). The percentage of A:T to G:C transitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European tumors). The frequency of mutations at CpG sites (14%) varied significantly from the 67% in cases from a neighboring region in Italy. Helicobacter pylori infection was established in 19 cases and was somewhat more common in cases lacking a p53 mutation. C1 NCI,FREDERICK CANC RES & DEV CTR,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,FREDERICK,MD 21702. CTR STUDIO & PREVENZ ONCOL,EPIDEMIOL UNIT,FLORENCE,ITALY. UNIV FLORENCE,DEPT PATHOL,FLORENCE,ITALY. CTR STUDIO & PREVENZ ONCOL,SEZ DISTACCATA IST,FLORENCE,ITALY. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. OI PALLI, Domenico/0000-0002-5558-2437 NR 57 TC 118 Z9 120 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 JUN 15 PY 1995 VL 55 IS 12 BP 2665 EP 2672 PG 8 WC Oncology SC Oncology GA RC936 UT WOS:A1995RC93600035 PM 7780983 ER PT J AU LENFANT, C AF LENFANT, C TI THE CALCIUM-CHANNEL BLOCKER SCARE - LESSONS FOR THE FUTURE SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 32 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 15 PY 1995 VL 91 IS 12 BP 2855 EP 2856 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RD516 UT WOS:A1995RD51600001 PM 7796490 ER PT J AU DETRE, K YEH, W KELSEY, S WILLIAMS, D DESVIGNENICKENS, P HOLMES, D BOURASSA, M KING, S FAXON, D KENT, K AF DETRE, K YEH, W KELSEY, S WILLIAMS, D DESVIGNENICKENS, P HOLMES, D BOURASSA, M KING, S FAXON, D KENT, K TI HAS IMPROVEMENT IN PTCA INTERVENTION AFFECTED LONG-TERM PROGNOSIS - THE NHLBI PTCA REGISTRY EXPERIENCE SO CIRCULATION LA English DT Article DE ANGIOPLASTY; REGISTRIES; FOLLOW-UP STUDIES ID LUMINAL CORONARY ANGIOPLASTY; MULTIVESSEL DISEASE; ARTERY DISEASE; PATIENT SELECTION; DETERMINANTS; SURGERY; SINGLE; TRIAL AB Background The NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry followed 1345 consecutive patients with first PTCA between 1977 and 1981 (registry 1) and 2136 consecutive patients with PTCA between 1985 and 1986 (registry 2). Changes in patient selection and in immediate and 1-year outcome are presented. This report extends to 5 years the comparison of the effects of early and more recent management with PTCA. Methods and Results Sixteen participating centers entered consecutive patients who had angioplasty for the first time between 1977 and 1981 and between 1985 and 1986. Patients with recent myocardial infarction (MI) were excluded. Vessel disease was defined according to the Coronary Artery Surgery Study. Successful dilatation required greater than or equal to 20% reduction in luminal narrowing and <50% lumen diameter stenosis after intervention. Routine annual follow-up was conducted by telephone interview. The product-limit method was used to estimate freedom from untoward events, Cox regression analysis to model relative risk and adjusted relative risk of events between the two registries, and logistic regression when the exact time of outcome (such as recurrence of symptoms) was not known. Long-term event rates were computed by vessel disease for all patients and for the cohort of patients with initially successful PTCA. After adjustment for extent of disease, diabetes, prior bypass surgery (CABG), hypertension, age, and sex, the 5-year risk of death was similar in the two registry cohorts. However, rates of MI, CABG, and a combined outcome measure of death, MI, and/or CABG were significantly lower in the registry 2 cohort both for all patients and for patients who were initially treated successfully. Use of repeated PTCA was higher, and freedom from symptoms without adverse events was significantly better in the latter cohort. Conclusions Compared with registry 1, the management of the registry 2 cohort resulted in lower 5-year morbid event rates and reduced CABG operations. Mortality rates remained similar. When symptomatic status was considered in combination with events, a significantly better outcome was seen overall and in the initially successful cohort. In registry 2, repeated PTCA was used with much greater frequency early after the initial procedure. C1 RHODE ISL HOSP, PROVIDENCE, RI 02902 USA. NHLBI, BETHESDA, MD 20892 USA. MAYO CLIN, ROCHESTER, MN USA. MONTREAL HEART INST, MONTREAL, PQ H1T 1C8, CANADA. EMORY UNIV, ATLANTA, GA 30322 USA. UNIV SO CALIF, LOS ANGELES, CA USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. RP DETRE, K (reprint author), UNIV PITTSBURGH, A531 CRABTREE HALL GSPH, PITTSBURGH, PA 15261 USA. OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HL-33292] NR 30 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 15 PY 1995 VL 91 IS 12 BP 2868 EP 2875 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RD516 UT WOS:A1995RD51600005 PM 7796494 ER PT J AU URFER, R TSOULFAS, P OCONNELL, L SHELTON, DL PARADA, LF PRESTA, LG AF URFER, R TSOULFAS, P OCONNELL, L SHELTON, DL PARADA, LF PRESTA, LG TI AN IMMUNOGLOBULIN-LIKE DOMAIN DETERMINES THE SPECIFICITY OF NEUROTROPHIN RECEPTORS SO EMBO JOURNAL LA English DT Article DE BINDING DOMAIN; NEUROTROPHINS; TRK; TYROSINE KINASE RECEPTOR ID NERVE GROWTH-FACTOR; TYROSINE KINASE RECEPTORS; TRK PROTOONCOGENE PRODUCT; CRYSTAL-STRUCTURE; RESOLUTION; PATTERNS; NEURONS; BINDING; ENCODES; MOTIFS AB The neurotrophins influence survival and maintenance of vertebrate neurons in the embryonic, early postnatal and post-developmental stages of the nervous system. Binding of neurotrophins to receptors encoded by the gene family trk initiates signal transduction into the cell, trkA interacts preferably with nerve growth factor (NGF), trkB with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and trkC with neurotrophin-3 (NT-3), By constructing 17 different chimeras and domain deletions of the human trk receptors and analyzing their binding affinities to the neurotrophins we have shown that an immunoglobulin-like domain located adjacent to the transmembrane domain is the structural element that determines the interaction of neurotrophins with their receptors. Chimeras of trkC where this domain was exchanged for the homologous sequences from trkB or trkA gained high affinity binding to BDNF or NGF respectively, while deletion of this domain in trkC or trkA abolished binding to NT-3 or NGF respectively, This domain alone retained affinities to neurotrophins similar to the full-length receptors and when expressed on NIH 3T3 cells in fusion with the kinase domain showed neurotrophin-dependent activation. C1 GENENTECH INC,DEPT NEUROSCI,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RP URFER, R (reprint author), GENENTECH INC,DEPT PROT ENGN,460 POINT SAN BRUNO BLVD,S SAN FRANCISCO,CA 94080, USA. RI Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 FU PHS HHS [N01-C0-74101] NR 43 TC 112 Z9 113 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1995 VL 14 IS 12 BP 2795 EP 2805 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RF900 UT WOS:A1995RF90000011 PM 7796806 ER PT J AU YOSHIMURA, A OHKUBO, T KIGUCHI, T JENKINS, NA GILBERT, DJ COPELAND, NG HARA, T MIYAJIMA, A AF YOSHIMURA, A OHKUBO, T KIGUCHI, T JENKINS, NA GILBERT, DJ COPELAND, NG HARA, T MIYAJIMA, A TI A NOVEL CYTOKINE-INDUCIBLE GENE CIS ENCODES AN SH2-CONTAINING PROTEIN THAT BINDS TO TYROSINE-PHOSPHORYLATED INTERLEUKIN-3 AND ERYTHROPOIETIN RECEPTORS SO EMBO JOURNAL LA English DT Article DE CYTOKINE; CYTOKINE RECEPTOR; IMMEDIATE-EARLY GENE; SH2 DOMAIN ID GROWTH SIGNAL TRANSDUCTION; COMMON BETA-SUBUNIT; GM-CSF; MONOCLONAL-ANTIBODIES; IL-3 RECEPTOR; DOMAIN; RAS; SEQUENCES; REGIONS; CHAIN AB Cytokines manifest their function through alteration of gene expression, However, target genes for signals from cytokine receptors are largely unknown, We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle, To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter, The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation, Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. KAGOSHIMA UNIV,FAC MED,CANC RES INST,KAGOSHIMA 890,JAPAN. KURUME UNIV,INST LIFE SCI,KURUME,FUKUOKA 830,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,TOKYO 113,JAPAN. RI Yoshimura, Akihiko/K-5515-2013 FU NCI NIH HHS [N01-CO-74101] NR 52 TC 530 Z9 553 U1 2 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1995 VL 14 IS 12 BP 2816 EP 2826 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RF900 UT WOS:A1995RF90000013 PM 7796808 ER PT J AU ZHOU, SB YANG, YF SCOTT, MJ PANNUTI, A FEHR, KC EISEN, A KOONIN, EV FOUTS, DL WRIGHTSMAN, R MANNING, JE LUCCHESI, JC AF ZHOU, SB YANG, YF SCOTT, MJ PANNUTI, A FEHR, KC EISEN, A KOONIN, EV FOUTS, DL WRIGHTSMAN, R MANNING, JE LUCCHESI, JC TI MALE-SPECIFIC LETHAL-2, A DOSAGE COMPENSATION GENE OF DROSOPHILA, UNDERGOES SEX-SPECIFIC REGULATION AND ENCODES A PROTEIN WITH A RING FINGER AND A METALLOTHIONEIN-LIKE CYSTEINE CLUSTER SO EMBO JOURNAL LA English DT Article DE HYPERTRANSCRIPTION; SPLICING; X CHROMOSOME BINDING ID DNA-BINDING PROTEIN; X-CHROMOSOME; ZINC-FINGER; DETERMINATION SIGNAL; SECONDARY STRUCTURE; TRANSFORMER GENE; SPLICE SITE; MELANOGASTER; TRANSCRIPTION; RNA AB In Drosophila the equalization of X-linked gene products between males and females, i.e. dosage compensation, is the result of a 2-fold hypertranscription of most of these genes in males, At least four regulatory genes are required for this process, Three of these genes, maleless (mle), male-specific lethal 1 (msl-1) and male-specific lethal 3 (msl-3), have been cloned and their products have been shown to interact and to bind to numerous sites on the X chromosome of males, but not of females, Although binding to the X chromosome is negatively correlated with the function of the master regulatory gene Sex lethal (Sxl), the mechanisms that restrict this binding to males and to the X chromosome are not yet understood, We have cloned the last of the known autosomal genes involved in dosage compensation, male-specific lethal 2 (msl-2), and characterized its product, The encoded protein (MSL-2) consists of 769 amino acid residues and has a RING finger (C3HC4 zinc finger) and a metallothionein-like domain with eight conserved and two non-conserved cysteines, In addition, it contains a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions, Males produce a msl-2 transcript that is shorter than in females, due to differential splicing of an intron of 132 bases in the untranslated leader, Using an antiserum against MSL-2 we have shown that the protein is expressed at a detectable level only in males, where it is physically associated with the X chromosome, Our observations suggest that MSL-2 may be the target of the master regulatory gene Sxl and provide the basic elements of a working hypothesis on the function of MSL-2 in mediating the 2-fold increase in transcription that is characteristic of dosage compensation. C1 EMORY UNIV,DEPT BIOL,ATLANTA,GA 30322. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. UNIV CALIF IRVINE,DEPT MOLEC BIOL & BIOCHEM,IRVINE,CA 92717. RI Scott, Maxwell/J-1935-2015 OI Scott, Maxwell/0000-0001-6536-4735 FU NIGMS NIH HHS [GM15691] NR 61 TC 126 Z9 128 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1995 VL 14 IS 12 BP 2884 EP 2895 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RF900 UT WOS:A1995RF90000020 PM 7796814 ER PT J AU TJANDRA, N KUBONIWA, H REN, H BAX, A AF TJANDRA, N KUBONIWA, H REN, H BAX, A TI ROTATIONAL-DYNAMICS OF CALCIUM-FREE CALMODULIN STUDIED BY N-15-NMR RELAXATION MEASUREMENTS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE CALMODULIN; NMR; PROTEIN DYNAMICS; N-15 RELAXATION; DOMAIN MOTION ID MODEL-FREE APPROACH; MAGNETIC-RESONANCE RELAXATION; NMR-SPECTROSCOPY; TROPONIN-C; BACKBONE DYNAMICS; HETERONUCLEAR NMR; SKELETAL-MUSCLE; MULTIDIMENSIONAL NMR; HYDROGEN-EXCHANGE; CROSS-CORRELATION AB The backbone motions of calcium-free Xenopus calmodulin have been characterized by measurements of the N-15 longitudinal relaxation times (T-1) at 51 and 61 MHz, and by conducting transverse relaxation (T-2), spin-locked transverse relaxation (T-1 rho), and N-15-{H-1} heteronuclear NOE measurements at 61 MHz N-15 frequency. Although backbone amide hydrogen exchange experiments indicate that the N-terminal domain is more stable than calmodulin's C-terminal half, slowly exchanging backbone amide protons are found in all eight alpha-helices and in three of the four short beta-strands. This confirms that the calcium-free form consists of stable secondary structure and does not adopt a 'molten globule' type of structure. However, the C-terminal domain of calmodulin is subject to conformational exchange on a time scale of about 350 mu s, which affects many of the C-terminal domain residues. This results in significant shortening of the N-15 T-2 values relative to T-1 rho, whereas the T-1 rho and T-2 values are of similar magnitude in the N-terminal half of the protein. A model in which the motion of the protein is assumed to be isotropic suggests a rotational correlation time for the protein of about 8 ns but quantitatively does not agree with the magnetic field dependence of the T-1 values and does not explain the different T, values found for different alpha-helices in the N-terminal domain. These latter parameters are compatible with a flexible dumbbell model in which each of calmodulin's two domains freely diffuse in a cone with a semi-angle of about 30 degrees and a time constant of about 3 ns, whereas the overall rotation of the protein occurs on a much slower time scale of about 12 ns. The difference in the transverse relaxation rates observed between the amides in helices C and D suggests that the change in interhelical angle upon calcium binding is less than predicted by Herzberg et al. Strynadka and James [Strynadka, N. C. J. and James, M. N. G. (1988) Proteins Struct. Funct. Genet. 3, 1-17]. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [1F32DK09143-01] NR 58 TC 231 Z9 231 U1 1 U2 9 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN 15 PY 1995 VL 230 IS 3 BP 1014 EP 1024 DI 10.1111/j.1432-1033.1995.tb20650.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RF162 UT WOS:A1995RF16200024 PM 7601131 ER PT J AU MAOR, MH ERRINGTON, RD CAPLAN, RJ GRIFFIN, TW LARAMORE, GE PARKER, RG BURNISON, M STETZ, J ZINK, S DAVIS, LW PETERS, LJ AF MAOR, MH ERRINGTON, RD CAPLAN, RJ GRIFFIN, TW LARAMORE, GE PARKER, RG BURNISON, M STETZ, J ZINK, S DAVIS, LW PETERS, LJ TI FAST-NEUTRON THERAPY IN ADVANCED HEAD AND NECK-CANCER - A COLLABORATIVE INTERNATIONAL RANDOMIZED TRIAL SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE HEAD AND NECK CANCER; NEUTRON THERAPY; RANDOMIZED TRIAL ID ADVANCED TUMORS; CLINICAL-TRIAL; FINAL REPORT; GAMMA-RAYS AB Purpose: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. Methods and Materials: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. Results: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). Conclusion: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity. C1 CLATTERBRIDGE CTR ONCOL,WIRRAL,MERSEYSIDE,ENGLAND. MRC,DOUGLAS CYCLOTRON CTR,LONDON W1N 4AL,ENGLAND. AMER COLL RADIOL,PHILADELPHIA,PA. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. EMORY CLIN,ATLANTA,GA. NCI,BETHESDA,MD 20892. RP MAOR, MH (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOTHERAPY,BOX 97,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CM57775, CA16672, CA06294] NR 9 TC 35 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1995 VL 32 IS 3 BP 599 EP 604 DI 10.1016/0360-3016(94)00595-C PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RE533 UT WOS:A1995RE53300004 PM 7790244 ER PT J AU PODGORNIK, R AKESSON, T JONSSON, B AF PODGORNIK, R AKESSON, T JONSSON, B TI COLLOIDAL INTERACTIONS MEDIATED VIA POLYELECTROLYTES SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DOUBLE-LAYER FORCES; MONTE-CARLO; VARIATIONAL APPROACH; POISSON-BOLTZMANN; CHARGED SURFACES; CHAINS; ELECTROLYTE; SIMULATION; MICELLES; POLYMERS C1 CHEM CTR LUND,S-22100 LUND,SWEDEN. RP PODGORNIK, R (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 30 TC 47 Z9 47 U1 0 U2 2 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 JUN 15 PY 1995 VL 102 IS 23 BP 9423 EP 9434 DI 10.1063/1.468810 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA RD124 UT WOS:A1995RD12400031 ER PT J AU MAURER, D EBNER, C REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G AF MAURER, D EBNER, C REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G TI THE HIGH-AFFINITY IGE RECEPTOR (FC-EPSILON-RI) MEDIATES IGE-DEPENDENT ALLERGEN PRESENTATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; BIRCH POLLEN ALLERGEN; BET-V-I; OVERLAPPING PEPTIDES; ATOPIC-DERMATITIS; BINDING-PROTEIN; MAJOR ALLERGEN; LATE-PHASE; MACROPHAGES; EXPRESSION AB The discovery that the high affinity IgE receptor (Fc epsilon RI) is expressed on APCs of patients with atopic diseases raised the possibility that the functional importance of Fc epsilon RI in the pathogenesis of atopy may extend beyond its role in type I allergic reactions. Here we show that, following removal of in vivo-bound IgE by lactic acid treatment, targeting of allergens to monocytes by Ag-specific IgE critically depends on Fc epsilon RI expression. Even more importantly, lactic acid-treated, monocyte-enriched PBMCs present allergen to T cells 100- to 1000-fold more effectively if the allergen has been targeted to Fc epsilon RI on these cells via allergen-specific IgE. This mechanism may critically lower the atopic individual's threshold to mount allergen-specific T cell responses capable of promoting IgE production and delayed-type hypersensitivity reactions. C1 UNIV VIENNA,SCH MED,INST GEN & EXPTL PATHOL,DIV IMMUNOPATHOL,A-1090 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. RP MAURER, D (reprint author), UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,WAEHRINGER GUERTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 28 TC 263 Z9 267 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1995 VL 154 IS 12 BP 6285 EP 6290 PG 6 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000008 PM 7759866 ER PT J AU VANMEERWIJK, JPM OCONNELL, EM GERMAIN, RN AF VANMEERWIJK, JPM OCONNELL, EM GERMAIN, RN TI EVIDENCE FOR LINEAGE COMMITMENT AND INITIATION OF POSITIVE SELECTION BY THYMOCYTES WITH INTERMEDIATE SURFACE PHENOTYPES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; DETERMINE IMMUNE RESPONSIVENESS; ANTIGEN-PRESENTING CELLS; NEGATIVE SELECTION; TRANSGENIC MICE; CLONAL DELETION; CD8 LINEAGES; CD4+CD8+ THYMOCYTES; HEMATOPOIETIC-CELLS AB Previous studies have shown that both MHC class I and class II molecules can stimulate CD4(+)CD8(+) thymocytes to develop into TCR(int) cells with surface phenotypes, suggesting initial differentiation along either the CD4 or CD8 developmental pathways. In accord with the view that these cells have undergone lineage commitment, we show here that CD4(int)TCR(int) cells generated by recognition of either MHC class show the same partial dawn-regulation of CD8 from the level on precursor double positive thymocytes as do almost mature CD4(int)TCR(high) cells positively selected only by MHC class I recognition. As expected of cells undergoing positive selection, we find that either class I or class II MHC molecules on radioresistant thymic stromal cells alone are sufficient for generation of both types of transitional phenotype cells, Biases in V beta representation associated with allele-dependent positive selection are seen only in the TCR(high) and not the TCR(int) cohorts, however. These findings are consistent with the hypothesis that transitional phenotype thymocytes have begun but not completed positive selection, and that entry into the CD4 vs CD8 pathways is not uniquely determined by the specific coreceptor-MHC molecule interaction involved in precursor thymocyte activation. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RI van Meerwijk, Joost/K-1345-2014 NR 53 TC 24 Z9 24 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 JUN 15 PY 1995 VL 154 IS 12 BP 6314 EP 6323 PG 10 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000012 PM 7759870 ER PT J AU CHEN, HT ALEXANDER, CB MAGE, RG AF CHEN, HT ALEXANDER, CB MAGE, RG TI CHARACTERIZATION OF A RABBIT GERM-LINE V-H GENE THAT IS A CANDIDATE DONOR FOR V-H GENE CONVERSION IN MUTANT ALICIA RABBITS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIBODY DIVERSITY; SOMATIC DIVERSIFICATION; VHA2 ALLOTYPE; CHAIN; CHICKEN; REGION; EXPRESSION; SEQUENCES; GENERATION; REPERTOIRE AB Normal rabbits preferentially rearrange the 3'-most V-H gene, V(H)1, to encode Igs with V(H)a allotypes, which constitute the majority of rabbit serum Igs. A gene conversion-like mechanism is employed to diversify the primary Ab repertoire. In mutant Alicia rabbits that derived from a rabbit with V(H)a2 allotype, the V(H)1 gene was deleted. Our previous studies showed that the first functional gene (V(H)4) or V(H)1-like genes were rearranged in 2- to 8-wk-old homozygous Alicia. The V(H)1a2-like sequences that were found in splenic mRNA from 6-wk and older Alicia rabbits still had some residues that were typical of V(H)4. The appearances of sequences resembling that of V(H)1a2 may have been caused by gene conversions that altered the sequences of the rearranged V-H or there may have been rearrangement of upstream V(H)1a2-like genes later in development. To investigate this further, we constructed a cosmid library and isolated a V(H)1a2-like gene, V(H)12-1-6, with a sequence almost identical to V(H)1a2. This gene had a deleted base in the heptamer of its recombination signal sequence. However, even if this defect diminished or eliminated its ability to rearrange, the a2-like gene could have acted as a donor for gene-conversion-like alteration of rearranged V-H genes. Sequence comparisons suggested that this gene or a gene like it could have acted as a donor for gene conversion in mutant Alicia and in normal rabbits. C1 NIAID,IMMUNOL LAB,IMMUNOGENET MOLEC LAB,BETHESDA,MD 20892. NR 35 TC 9 Z9 9 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 JUN 15 PY 1995 VL 154 IS 12 BP 6365 EP 6371 PG 7 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000017 PM 7759874 ER PT J AU KUHNS, DB GALLIN, JI AF KUHNS, DB GALLIN, JI TI INCREASED CELL-ASSOCIATED IL-8 IN HUMAN EXUDATIVE AND A23187-TREATED PERIPHERAL-BLOOD NEUTROPHILS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ACTIVATING FACTOR; SUBCELLULAR-LOCALIZATION; ALKALINE-PHOSPHATASE; RELEASE; INTERLEUKIN-8; PURIFICATION; EXPRESSION; ADHERENCE; PROTEINS AB IL-8 is a potent neutrophil chemoattractant that has been detected in high concentrations at acutely inflamed sites in vivo. Many cell types, including peripheral blood neutrophils, produce IL-8 that can be released by a variety of pro-inflammatory stimuli. However, the functional importance of neutrophil IL-8 during exudation is not yet known. We now report that neutrophils, harvested from skin lesions on the forearms of normal human volunteers (exudative neutrophils), expressed 100-fold higher levels of cell-associated IL-8 and spontaneously released up to 50-fold more IL-8 than freshly isolated peripheral blood neutrophils from the same donor. Furthermore, cell-associated IL-8 in peripheral blood neutrophils increased 20-fold during incubation at 37 degrees C in vitro and was increased over 200-fold after treatment with the Ca2+ ionophore A23187. More than 35% of the cell-associated IL-8 could be released by stimulation with either Ca2+ ionophore A23187 or phorbol myristate acetate. IL-8 was localized by sucrose gradient centrifugation to a subcellular fraction of heterogeneous, light membranous organelles. The accumulation of IL-8 within these organelles is inhibited by cycloheximide but not actinomycin D, suggesting that IL-8 accumulation is under translational, rather than transcriptional control. These studies indicate that peripheral blood neutrophils are capable of synthesis of large amounts of IL-8. Subsequent release of IL-8 during exudation may regulate neutrophil migration into sites of inflammation. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 23 TC 34 Z9 36 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 JUN 15 PY 1995 VL 154 IS 12 BP 6556 EP 6562 PG 7 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000039 PM 7759889 ER PT J AU BONOMO, A KEHN, PJ PAYER, E RIZZO, L CHEEVER, AW SHEVACH, EM AF BONOMO, A KEHN, PJ PAYER, E RIZZO, L CHEEVER, AW SHEVACH, EM TI PATHOGENESIS OF POST-THYMECTOMY AUTOIMMUNITY - ROLE OF SYNGENEIC MLR-REACTIVE T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; NEONATAL THYMECTOMY; B-CELLS; SELF-TOLERANCE; THYMUS; MICE; EXPRESSION; DISEASE; MEMORY; VIRGIN AB Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4(+) T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4(+) T cells that remain in the 3-day thymectomized animal revealed that the majority (similar to 80%) of the CD4(+) lymph node cells express an activated (MEL-14(low)) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4(+) IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NEI,IMMUNOL LAB,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 NR 39 TC 62 Z9 63 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 JUN 15 PY 1995 VL 154 IS 12 BP 6602 EP 6611 PG 10 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000044 PM 7759894 ER PT J AU BOYLE, MJ CONNORS, M FLANIGAN, ME GEIGER, SP FORD, H BASELER, M ADELSBERGER, J DAVEY, RT LANE, HC AF BOYLE, MJ CONNORS, M FLANIGAN, ME GEIGER, SP FORD, H BASELER, M ADELSBERGER, J DAVEY, RT LANE, HC TI THE HUMAN HIV PERIPHERAL-BLOOD LYMPHOCYTE (PBL)-SCID MOUSE - A MODIFIED HUMAN PBL-SCID MODEL FOR THE STUDY OF HIV PATHOGENESIS AND THERAPY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4+ T-CELLS; HU MOUSE; MICE; INFECTION; DEATH; EXPRESSION; DEPLETION; CLONING; DISEASE AB PBL from HIV-infected patients were engrafted into CB-17 SCID mice to develop a novel small animal model for the study of HIV pathogenesis and therapy. Engraftment was achieved in 84% of mice, with human Ig (hu-lg) levels and total human mononuclear cell recovery by peritoneal wash similar to those in control hu-PBL-SCID mice engrafted with un infected donor cells. The hu-lg produced by hu-HIV/PBL-SCID mice had broad reactivity against HIV. Virus could be detected in 98% of mice by polymerase chain reaction and/or viral coculture. Viremia was first detected by quantitative polymerase chain reaction on day 7 (approximately 10,000 copies of viral RNA/ml of plasma) and persisted through day 17. Quasispecies analysis of amplified, cloned, proviral DNA of the V3 region of the env gene showed that nucleotide sequences from hu-HIV/PBL-SCID mouse peritoneal wash cells on day 17 were not significantly changed from those derived from donor PBL at the time of injection. Relative to human CD4(+) T cell recovery by peritoneal wash in control hu-PBL-SCID mice (CD4 = 19 +/- 2%; n 40), severe CD4(+) lymphocyte depletion (CD4 = 5 +/- 0.5%; n = 59; p < 0.001) was observed in untreated hu-HIV/PBL-SCID mice 18 to 25 days after engraftment. Treatment with 2'-beta-fluoro-2',3'-dideoxyadenosine, a nucleoside analogue, significantly reduced CD4(+) T cell depletion (CD4 = 13 +/- 1; n = 59; p < 0.001) and the frequency of virus isolation (70%; p = 0.015) in the hu-HIV/PBL-SCID model. Boosting hu-lg levels in the mice by injection of purified donor Ig with neutralizing activity did not affect the frequency of CD4(+) lymphocyte recovery or virus isolation. The administration of a mAb to TNF had minimal effects. These studies demonstrate that PBL from HIV-infected donors can engraft SCID mice; that HIV can be detected in the spleen, peritoneal wash cells, and blood of these mice; that HIV infection within the model results in rapid CD4(+) T cell depletion; and that antiretroviral therapy is effective in improving CD4(+) T cell recovery and reducing the frequency of virus isolation. The hu-HIV/PBL-SCID mouse model thus represents a potentially useful model in which to study HIV pathogenesis and therapy. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. PRI DYNCORP,FREDERICK,MD 21702. NR 38 TC 21 Z9 24 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 JUN 15 PY 1995 VL 154 IS 12 BP 6612 EP 6623 PG 12 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000045 PM 7759895 ER PT J AU PINET, V VERGELLI, M MARTIN, R BAKKE, O LONG, EO AF PINET, V VERGELLI, M MARTIN, R BAKKE, O LONG, EO TI ANTIGEN PRESENTATION MEDIATED BY RECYCLING OF SURFACE HLA-DR MOLECULES SO NATURE LA English DT Article ID CLASS-II MOLECULES; INVARIANT-CHAIN; PROTEIN-SYNTHESIS; MHC MOLECULES; MICE LACKING; LIVING CELLS; ENDOCYTOSIS; PEPTIDES; EXPRESSION; IA AB CLASS II histocompatibility molecules associate with peptides derived from antigens that are processed in endocytic compartments. Antigen presentation to class II-restricted T cells generally requires newly synthesized class II molecules(1), associated invariant chain(2,3), and HLA-DM(4,5). Exceptions to these rules have been reported(6-10), but without description of an underlying mechanism. Here we show that presentation of immunodominant epitopes in the haemagglutinin protein of influenza virus and in myelin basic protein correlates,vith recycling of surface KLA-DR molecules. Truncation of either one of the alpha or beta cytoplasmic tails virtually eliminated internalization of HLA-DR molecules and presentation of haemagglutinin from inactive virus particles. In contrast, the invariant chain-dependent presentation of matrix antigen from the same virus particles was unaffected by these truncations. Thus HLA-DR cytoplasmic tails are not required for the conventional presentation pathway, but jointly contribute a signal for an alternative pathway involving internalization of HLA-DR molecules. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. UNIV OSLO,DEPT BIOL,N-0316 OSLO,NORWAY. RI Long, Eric/G-5475-2011; PINET, Valerie/G-6085-2012 OI Long, Eric/0000-0002-7793-3728; NR 30 TC 227 Z9 228 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 15 PY 1995 VL 375 IS 6532 BP 603 EP 606 DI 10.1038/375603a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RD287 UT WOS:A1995RD28700055 PM 7540726 ER PT J AU PANTALEO, G FAUCI, AS AF PANTALEO, G FAUCI, AS TI LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP PANTALEO, G (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 15 PY 1995 VL 332 IS 24 BP 1648 EP 1648 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RC192 UT WOS:A1995RC19200017 ER PT J AU MACKALL, CL STEINBERG, SM GRESS, RE AF MACKALL, CL STEINBERG, SM GRESS, RE TI REGENERATION OF T-CELLS AFTER CHEMOTHERAPY - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MACKALL, CL (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 15 PY 1995 VL 332 IS 24 BP 1652 EP 1652 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RC192 UT WOS:A1995RC19200028 ER PT J AU WEINBERG, WC AZZOLI, CG CHAPMAN, K LEVINE, AJ YUSPA, SH AF WEINBERG, WC AZZOLI, CG CHAPMAN, K LEVINE, AJ YUSPA, SH TI P53-MEDIATED TRANSCRIPTIONAL ACTIVITY INCREASES IN DIFFERENTIATING EPIDERMAL-KERATINOCYTES IN ASSOCIATION WITH DECREASED P53 PROTEIN SO ONCOGENE LA English DT Article DE P53; EPIDERMIS; DIFFERENTIATION; TRANSCRIPTIONAL ACTIVATION; WAF1; MDM-2 ID WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; LARGE T-ANTIGEN; DNA-BINDING; MONOCLONAL-ANTIBODIES; MALIGNANT PROGRESSION; ACTIVATING MUTATIONS; CELL-DIFFERENTIATION; EPITHELIAL-CELLS; GROWTH-FACTOR AB The regulation of p53 protein synthesis and p53-mediated gene transactivation mere evaluated in cultured mouse keratinocytes maintained as basal cells or induced to differentiate by Ca2+>0.1 mM. p53 protein half-life, p53 protein synthesis and the level of p53 mRNA decreased during terminal differentiation, as detected by immunoprecipitation ,vith a panel of p53-specific antibodies and Northern blotting. Thus differentiating keratinocytes have lower levels of p53 protein. This decline is not observed following growth arrest alone, or in papilloma cell lines which do not terminally differentiate in response to Ca2+. In contrast, the ability of endogenous p53 to transactivate transcription from the PGI, CAT plasmid increased during differentiation in vitro. This change in activity cannot be explained by changes in p53 conformation or nuclear localization. Consistent with these findings, mRNA for the p53-mediated genes WAF1 and mdm-2 increased with Ca2+-induced differentiation in a time dependent manner, suggesting activation of p53 contributes to the differentiated phenotype. However, p53-null mice exhibit histologically normal skin and epidermal keratinocytes from these mice express the appropriate markers of differentiation and suppression of DNA synthesis in vitro when the [Ca2+] is >0.1 mM. The observation that proliferating cells have higher levels of p53 protein which is less active for its function than differentiated cell types could have a consequence for the selection of p53 gene mutations during carcinogenesis, depending upon the stage of differentiation of the tumor cell type. C1 PRINCETON UNIV,DEPT MOLEC BIOL,LEWIS THOMAS LAB,PRINCETON,NJ 08544. RP WEINBERG, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 90 TC 101 Z9 102 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 15 PY 1995 VL 10 IS 12 BP 2271 EP 2279 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RE543 UT WOS:A1995RE54300001 PM 7784075 ER PT J AU KEANE, MM RIVEROLEZCANO, OM MITCHELL, JA ROBBINS, KC LIPKOWITZ, S AF KEANE, MM RIVEROLEZCANO, OM MITCHELL, JA ROBBINS, KC LIPKOWITZ, S TI CLONING AND CHARACTERIZATION OF CBL-B - A SH3 BINDING-PROTEIN WITH HOMOLOGY TO THE C-CBL PROTOONCOGENE SO ONCOGENE LA English DT Article DE CBL-B; SK3 PROTEIN INTERACTIONS; MAMMARY CELLS; DIFFERENTIATION ID ACUTE PROMYELOCYTIC LEUKEMIA; MESSENGER-RNA; DNA-BINDING; ZINC FINGER; V-CBL; SACCHAROMYCES-CEREVISIAE; POINT MUTATIONS; RAR-ALPHA; GENE; SEQUENCE AB We have cloned a new gene, cbl-b, with homology to the c-cbl proto-oncogene. A large protein is predicted (approx, MW 108 000) that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a putative leucine zipper. There is striking nucleotide and amino acid homology to the c-cbl proto-oncogene most notably in the structural motifs described above. Cbl-b is expressed in normal and malignant mammary epithelial cells, in a variety of normal tissues, and in hematopoietic tissue and cell lines. Cbl-b expressions is up-regulated with macrophage/monocyte differentiation of the HL60 and U937 cell lines, There is direct association of the cbl-b protein with the Src Homology 3 domains of several proteins including signaling, cytoskeletal and adaptor proteins. Our data suggest that cbl-b encodes a protein which can interact with signal transduction proteins to regulate their function or to be regulated by them, Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction. C1 USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Rivero-Lezcano, Octavio/J-9089-2015 OI Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 43 TC 159 Z9 164 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 15 PY 1995 VL 10 IS 12 BP 2367 EP 2377 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RE543 UT WOS:A1995RE54300012 PM 7784085 ER PT J AU FOLLMANN, D AF FOLLMANN, D TI MULTIVARIATE TESTS FOR MULTIPLE END-POINTS IN CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article AB Clinical trials frequently lack a single definitive endpoint that completely describes treatment efficacy. When a treatment affects a disease in a multitude of ways, several endpoints are necessary to describe efficacy. There is a variety of statistical procedures to provide a single p-value when a treatment affects several endpoints. This paper reviews several procedures including Hotelling's T-2 test, an approximate likelihood ratio test (Tang et al.), the weighted version of O'Brien's test, tests involving the maximum of several test statistics, and a test based on the average of the maximum of several endpoints (Wittes). I propose a risk score test whose rejection boundary corresponds to a contour of constant risk. Calculations and simulation studies help to compare the different tests with an emphasis on the effect of non-standard alternatives, and on identifying settings where some tests may lack clinical relevance. RP FOLLMANN, D (reprint author), NHLBI,BIOSTAT RES BRANCH,FED BLDG ROOM 2A11,BETHESDA,MD 20892, USA. NR 8 TC 29 Z9 29 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1995 VL 14 IS 11 BP 1163 EP 1175 DI 10.1002/sim.4780141103 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA RE492 UT WOS:A1995RE49200002 PM 7667558 ER PT J AU BALDWIN, ET BHAT, TN GULNIK, S LIU, BS TOPOL, IA KISO, Y MIMOTO, T MITSUYA, H ERICKSON, JW AF BALDWIN, ET BHAT, TN GULNIK, S LIU, BS TOPOL, IA KISO, Y MIMOTO, T MITSUYA, H ERICKSON, JW TI STRUCTURE OF HIV-1 PROTEASE WITH KNI-272, A TIGHT-BINDING TRANSITION-STATE ANALOG CONTAINING ALLOPHENYLNORSTATINE SO STRUCTURE LA English DT Article DE ANTIVIRAL; DRUG DESIGN; DRUG RESISTANCE; HIV-1 PROTEASE; KNI-272; PROTEASE INHIBITOR ID INHIBITORS; ISOSTERE; COMPLEX; TARGET; AIDS AB Background: HIV-1 protease (HIV PR), an aspartic protease, cleaves Phe-Pro bonds in the Gag and Gag-Pol viral polyproteins. Substrate-based peptide mimics constitute a major class of inhibitors of HIV PR presently being developed for AIDS treatment. One such compound, KNI-272, which incorporates allophenylnorstatine (Apns)-thioproline (Thp) in place of Phe-Pro, has potent antiviral activity and is undergoing clinical trials. The structure of the enzyme-inhibitor complex should lead to an understanding of the structural basis for its tight binding properties and provide a framework for interpreting the emerging resistance to this drug. Results: The three-dimensional crystal structure of KNI-272 bound to HIV PR has been determined to 2.0 Angstrom resolution and used to analyze structure-activity data and drug resistance for the Arg8-->Gln and Ile84-->Val mutations in HIV PR. The conformationally constrained Apns-Thp linkage is favorably recognized in its low energy trans conformation, which results in a symmetric mode of binding to the active-site aspartic acids and also explains the unusual preference of HIV PR for the S, or syn, hydroxyl group of the Apns residue. The inhibitor recognizes the enzyme via hydrogen bonds to three bridging water molecules, including one that is coordinated directly to the catalytic Asp125 residue. Conclusions: The structure of the HIV PR/KNI-272 complex illustrates the importance of limiting the conformational degrees of freedom and of using protein-bound water molecules for building potent inhibitors. The binding mode of HIV PR inhibitors can be predicted from the stereochemical relationship between adjacent hydroxyl-bearing and side chain bearing carbon atoms of the P1 substituent. Our structure also provides a framework for designing analogs targeted to drug-resistant mutant enzymes. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. KYOTO PHARMACEUT UNIV,YAMASHIMA KU,KYOTO 607,JAPAN. JAPAN ENERGY CO,PHARMACEUT & BIOTECHNOL LAB,TODA,SAITAMA 335,JAPAN. NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NR 34 TC 131 Z9 132 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JUN 15 PY 1995 VL 3 IS 6 BP 581 EP 590 DI 10.1016/S0969-2126(01)00192-7 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RH535 UT WOS:A1995RH53500009 PM 8590019 ER PT J AU ZDANOV, A SCHALKHIHI, C GUSTCHINA, A TSANG, M WEATHERBEE, J WLODAWER, A AF ZDANOV, A SCHALKHIHI, C GUSTCHINA, A TSANG, M WEATHERBEE, J WLODAWER, A TI CRYSTAL-STRUCTURE OF INTERLEUKIN-10 REVEALS THE FUNCTIONAL DIMER WITH AN UNEXPECTED TOPOLOGICAL SIMILARITY TO INTERFERON-GAMMA SO STRUCTURE LA English DT Article DE CYTOKINES; 4-HELIX-BUNDLE; INTERLEUKIN-10; INTERFERON GAMMA; RECEPTOR BINDING ID CDNA CLONES; IL-10; RECEPTOR; RESOLUTION; REFINEMENT; MOUSE; MACROPHAGES; HOMOLOGY; BINDING; GROWTH AB Background: Interleukin (IL)-10 is a cytokine that inhibits production of ether regulatory factors, including interferon gamma (IFN gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic or antagonistic properties. Results: The X-ray crystal structure of a recombinant form of human IL-10 has been solved at 1.8 Angstrom resolution and refined to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of two interpene trating subunits, forming a V-shaped structure. Each half of the structure consists of six alpha-helices, four originating from one subunit and two from the other. Four of the helices form a classical 'up-up-down-down' bundle observed in all other helical cytokines. The overall topology of the helices bears close resemblance to IFN gamma, although the similarity is less striking when examined in greater detail. Conclusions: The topological similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection of the close relationship between the biological effects of these two cytokines. The structure of IL-10 provides insights into the possible modes of conversion of the dimer into monomers, and of putative sites of receptor interactions. The good level of refinement and high resolution of this structure show that the internal disorder often associated with other helical cytokines is not an essential feature of this class of proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. RES & DEV SYST,DIV BIOTECHNOL,MINNEAPOLIS,MN 55413. FU NCI NIH HHS [N01-CO-46000] NR 51 TC 162 Z9 173 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JUN 15 PY 1995 VL 3 IS 6 BP 591 EP 601 DI 10.1016/S0969-2126(01)00193-9 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RH535 UT WOS:A1995RH53500010 PM 8590020 ER PT J AU RESZKA, KJ CHIGNELL, CF AF RESZKA, KJ CHIGNELL, CF TI ONE-ELECTRON REDUCTION OF ARENEDIAZONIUM COMPOUNDS BY PHYSIOLOGICAL ELECTRON-DONORS GENERATES ARYL RADICALS - AN EPR AND SPIN-TRAPPING INVESTIGATION SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE ARYL RADICALS; DIAZONIUM COMPOUNDS; EPR; SPIN TRAPPING ID CUTANEOUS PHOTOSENSITIZING AGENTS; PHOTOLYSIS PRODUCTS; PHOTOCHEMICAL DECOMPOSITION; 4-AMINOBENZOIC ACID; AZO-COMPOUNDS; SALTS; SULFANILAMIDE; PRECURSORS; MECHANISM; IONS AB Arenediazonium compounds (ArN2+) are strong oxidizing agents, which upon one-electron reduction decompose, releasing aryl radicals (Ar-.). The present studies were undertaken to determine whether reductive fragmentation of ArN2+ can be induced by biologically relevant electron donors. We found that 4-X-Ph-N-2(+) (where X: -NO2, -Br, -Cl, -OMe and -N(Et)(2)) decomposes to the respective aryl radicals when reduced by ascorbate, NADH, potassium ferrocyanide, catechol or p-hydroquinone in aqueous solutions. Radical identification was based on analysis of the EPR spectra of spin adducts formed by reaction of these radicals with spin traps 2-methyl-2-nitrosopropane (MNP), 3,5-dibromo-4-nitrosobenzene sulphonate (DBNBS) or 5,5-dimethyl-1-pyrroline N-oxide (DMPO). This study shows that reduction of arenediazonium ions can be a convenient method for generating aryl radicals in aqueous solutions, In addition, this investigation confirms that biological reducing agents are capable of inducing fragmentation of ArN2+ into aryl radicals. This reaction may be pertinent to some biological actions of arenediazonium compounds. RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 34 Z9 34 U1 1 U2 6 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUN 14 PY 1995 VL 96 IS 3 BP 223 EP 234 DI 10.1016/0009-2797(94)03593-W PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA RA803 UT WOS:A1995RA80300002 PM 7750162 ER PT J AU RAUNIO, H HUSGAFVELPURSIAINEN, K ANTTILA, S HIETANEN, E HIRVONEN, A PELKONEN, O AF RAUNIO, H HUSGAFVELPURSIAINEN, K ANTTILA, S HIETANEN, E HIRVONEN, A PELKONEN, O TI DIAGNOSIS OF POLYMORPHISMS IN CARCINOGEN-ACTIVATING AND INACTIVATING ENZYMES AND CANCER SUSCEPTIBILITY - A REVIEW SO GENE LA English DT Article; Proceedings Paper CT Joint Meeting and Laboratory Course on Research in Gene Diagnostics of Cancer Disease CY OCT 24-28, 1994 CL MUNSTER, GERMANY DE ENVIRONMENTAL FACTORS; MODIFIERS; CYTOCHROME P-450; TOBACCO SMOKE; RFLP ID FRAGMENT-LENGTH-POLYMORPHISM; TRANSFERASE CLASS-MU; ARYLAMINE N-ACETYLTRANSFERASE; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER; GENETIC-POLYMORPHISM; BLADDER-CANCER; CYTOCHROME-P450IA1 GENE; CYP1A1 GENE; DNA ADDUCTS AB Up to 90% of all cancers are possibly caused by environmental factors, such as tobacco smoke, diet and occupational exposures. The majority of chemical carcinogens require metabolic activation before they interact with cellular macromolecules and can cause cancer initiation. The xenobiotic-metabolising machinery contains two main types of enzymes: the phase-I cytochromes P-450 (CYP) mediating oxidative metabolism, and phase-II conjugating enzymes. Several phase-I and phase-II genes have recently been cloned and identified in humans. Many of them show polymorphism and have been suggested to contribute to individual cancer susceptibility as genetic modifiers of cancer risk. Altered phenotypes and genotypes in the CYP subfamilies CYP1A1, CYP2D6 and CYP2E1 have been associated with tobacco smoke-induced lung cancer and other cancers. Defective glutathione S-transferase (GST) and N-acetyltransferase (NAT) enzymes have been associated with an increased risk of developing lung and bladder cancer. There are also several studies in each category in which no associations have been found, The risk of developing lung cancer is dramatically (up to 40-fold) elevated in subpopulations having simultaneously high-risk genotypes in CYP1A1 and GSTM1. There are several difficulties in this area of research. First, many of the observed restriction-fragment length polymorphisms (RFLPs) are due to mutations in introns or other silent areas of DNA, raising the possibility that any associations found between RFLPs and cancer occur only by chance. Second, biologically plausible mechanisms linking genotypes and cancer are lacking in most of the observed cases, Third, substantial ethnic differences have been shown to exist in the distribution of defective and functionally normal alleles, making extrapolations from one ethnic group to another impossible. Thus, it is still difficult to say to what extent tests based on the polymerase chain reaction (PCR) and other methodology will be used to in the future to predict an individual's susceptibility to cancers caused by xenobiotics. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. INST OCCUPAT HLTH,SF-00250 HELSINKI,FINLAND. UNIV TURKU,DEPT CLIN PHYSIOL,SF-20520 TURKU,FINLAND. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. NR 66 TC 215 Z9 234 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 14 PY 1995 VL 159 IS 1 BP 113 EP 121 DI 10.1016/0378-1119(94)00448-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA RG184 UT WOS:A1995RG18400015 PM 7607565 ER PT J AU GERSHON, PD KHILKO, S AF GERSHON, PD KHILKO, S TI STABLE CHELATING LINKAGE FOR REVERSIBLE IMMOBILIZATION OF OLIGOHISTIDINE TAGGED PROTEINS IN THE BIACORE SURFACE-PLASMON RESONANCE DETECTOR SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE BIACORE; HISTIDINE; NICKEL; METAL CHELATE; TRANSITION METAL COMPLEX ID BIOSPECIFIC INTERACTION ANALYSIS; RNA POLYMERASE-III; VACCINIA VIRUS; POLY(A) POLYMERASE; AFFINITY-CHROMATOGRAPHY; TRANSCRIPTION FACTORS; POLYADENYLATION; SUBUNIT; TAIL AB We describe a stable chelating linkage for the reversible immobilization of oligohistidine tagged proteins in the flow cell of the 'BIAcore' surface plasmon resonance (SPR) biosensor. The carboxymethylated dextran surface of the flow cell was covalently derivatized with N-(5-amino-1-carboxypentyl)iminodiacetic acid (NTA ligand) via its single primary amino group, and the derivatized surface charged with Ni2+. 6His-VP55, an N-terminally tagged derivative of the catalytic subunit of the heterodimeric vaccinia virus poly(A) polymerase, was immobilized to this surface in a manner that was dependent upon the immobilized NTA ligand, the prior injection of Ni2+ at a concentration of > 10(-5) M and the 6His tag, and which was reversible upon injection of EDTA. The stability of immobilization varied inversely with the amount of 6His-VP55 immobilized and was greatest in buffer of pH 8.0 or greater, containing NaCl at a concentration of 0.1 M. Utilizing these conditions, 6His-VP55 remained stably immobilized during 60 min of buffer flow at moderate flow rates. VP39, the stimulatory subunit of vaccinia poly(A) polymerase, interacted with the immobilized 6His-VP55. similar to 99% of immobilized 6His-VP55 molecules were available for VP39 binding, in contrast to the similar to 40% availability for 6His-VP55 molecules immobilized covalently, via primary amino groups. Three additional proteins, tagged at either the N- or C-terminus with oligohistidine, were shown to be stably immobilized via the chelating linkage. This simple method permits immobilization of proteins in the BIAcore biosensor via a commonly employed affinity tag, in a stable and reversible manner, and requires only a single biosensor flow cell for the iterative generation of immobilized protein surfaces. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP GERSHON, PD (reprint author), TEXAS A&M UNIV,ALBERT B ALKEK INST BIOSCI & TECHNOL,CTR GENOME RES,ROOM 817,2121 W HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 24 TC 103 Z9 103 U1 1 U2 19 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 JUN 14 PY 1995 VL 183 IS 1 BP 65 EP 76 DI 10.1016/0022-1759(95)00032-6 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RD985 UT WOS:A1995RD98500008 PM 7602140 ER PT J AU KHILKO, SN JELONEK, MT CORR, M BOYD, LF BOTHWELL, ALM MARGULIES, DH AF KHILKO, SN JELONEK, MT CORR, M BOYD, LF BOTHWELL, ALM MARGULIES, DH TI MEASURING INTERACTIONS OF MHC CLASS-I MOLECULES USING SURFACE-PLASMON RESONANCE SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX; SURFACE PLASMON RESONANCE; MONOCLONAL ANTIBODY ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RECEPTOR; CYTOTOXIC LYMPHOCYTES-T; VIRUS MATRIX PROTEIN; PEPTIDE BINDING; VIRAL PEPTIDES; MONOCLONAL-ANTIBODIES; ANTIGENIC PEPTIDE; HLA-A2; BETA-2-MICROGLOBULIN AB To examine the molecular interactions between major histocompatibility complex (MHC)-encoded molecules and peptides, monoclonal antibodies (mAbs), or T cell receptors, we have developed model systems employing genetically engineered soluble MHC class I molecules (MHC-I), synthetic peptides, purified mAbs, and engineered solubilizable T cell receptors. Direct binding assays based on immobilization of one of the interacting components to the dextran modified gold biosensor surface of a surface plasmon resonance (SPR) detector have been developed for each of these systems. The peptide binding site of the MHC-I molecule can be sterically mapped by evaluation of a set of peptides immobilized through the thiol group of cysteine substitutions at each peptide position. Kinetic binding studies indicate that the MHC-I/peptide interaction is characterized by a low to moderate apparent k(ass) (similar to 5000-60000 M(-1) s(-1)) and very small k(dis), (similar to 10(-4)-10(-6) s(-1)) consistent with the biological requirement for. long cell surface residence time to permit engagement with T cell receptors. Several mAb directed against different MHC-I epitopes were examined, and kinetic parameters of their interaction with MHC molecules were determined. These showed characteristic moderate association rate constants and moderate dissociation rate constants (k(ass) similar to 10(4)-10(6) M(-1) s(-1) and k(dis) similar to 10(-2)-10(-4) s(-1)), characteristic of many antibody/protein antigen interactions. The interaction of an anti-idiotypic anti-TCR mAb with its purified cognate TCR was of moderate affinity and revealed kinetic binding similar to that of the anti-MHC mAbs. The previously determined interaction of a purified T cell receptor with its MHC-I/peptide ligand is characterized by kinetic constants more similar to those of the antibody/antigen interaction than of the MHC-I/peptide interaction, but is remarkable for rapid dissociation rates (apparent k(dis) similar to 10(-2) s(-1)). Such binding studies of reactions involving the MHC-I molecules offer insight into the mechanisms responsible for the initial specific events required for the stimulation of T cells. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 51 TC 45 Z9 45 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 JUN 14 PY 1995 VL 183 IS 1 BP 77 EP 94 DI 10.1016/0022-1759(95)00033-7 PG 18 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RD985 UT WOS:A1995RD98500009 PM 7602142 ER PT J AU VANCOTT, TC VEIT, SCD KALYANARAMAN, V EARL, P BIRX, DL AF VANCOTT, TC VEIT, SCD KALYANARAMAN, V EARL, P BIRX, DL TI CHARACTERIZATION OF A SOLUBLE, OLIGOMERIC HIV-1 GP160 PROTEIN AS A POTENTIAL IMMUNOGEN SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE HIV-1 VACCINE; HIV-1 ENVELOPE GLYCOPROTEIN; GP120/GP160; BIACORE; HIV-1 IMMUNE RESPONSE; OLIGOMERIC GP160 ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING MONOCLONAL-ANTIBODIES; BIOSPECIFIC INTERACTION ANALYSIS; TYPE-1 ENVELOPE GLYCOPROTEIN; GP120; AIDS; ANTIGEN; VACCINE; BINDING; DOMAIN AB We have assessed the oligomeric structure and antigenic properties of an affinity purified gp160 protein (oligo-gp160) using biosensor technology. Sucrose gradient purification analysis identified the existence of tetrameric, dimeric and monomeric forms of the protein. Reactivity to a broad panel of monoclonal antibodies specific for oligomeric gp160, discontinuous epitopes within monomeric gp120 and several linear epitopes within gp120 (V3) and gp41 was demonstrated. International sera from several countries, where HIV-1 clades A-F are prevalent, including type O from Cameroon, were reactive with oligo-gp160 indicating conserved antigenic epitopes. Enhanced immunologic reactivity per gp160 molecule was obtained with oligo-gp160 as compared to other current HIV-1(IIIB) subunit monomeric envelope gp120/gp160 immunogens suggesting higher HIV-1 envelope protein mimicry. HIV-1 antibodies from sera during acute HIV-1 infection were detectable by oligo-gp160 prior to detection with either a recombinant, monomeric gp120 protein or several commercial HIV-1 screening kits suggesting antibodies sensitive to oligomeric gp160 structure may be present earlier in infection. The oligomeric nature of this gp160 protein preparation and high reactivity with divergent mAbs and HIV-1 sera support the use of this protein as an HIV-1 immunogen. C1 HENRY M JACKSON FDN,ROCKVILLE,MD 20850. ADV BIOSCI LABS,KENSINGTON,MD. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP VANCOTT, TC (reprint author), WALTER REED ARMY INST RES,DIV RETROVIROL,DEPT RETROVIRAL RES,13 TAFT CT,SUITE 200,ROCKVILLE,MD 20850, USA. NR 58 TC 40 Z9 41 U1 0 U2 2 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 JUN 14 PY 1995 VL 183 IS 1 BP 103 EP 117 DI 10.1016/0022-1759(95)00038-C PG 15 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RD985 UT WOS:A1995RD98500011 PM 7602128 ER PT J AU AUSTIN, JC FITZHUGH, A VILLAFRANCA, JE SPIRO, TG AF AUSTIN, JC FITZHUGH, A VILLAFRANCA, JE SPIRO, TG TI STEREOELECTRONIC ACTIVATION OF METHYLENETETRAHYDROFOLATE BY THYMIDYLATE SYNTHASE - RESONANCE RAMAN-SPECTROSCOPIC EVIDENCE SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; TERNARY COMPLEX; BINDING; SYNTHETASE; MECHANISM; ENZYME AB Resonance Raman (RR) spectra are reported for the ternary complex of Escherichia coli thymidylate synthase with the cofactor 5,10-methylenetetrahydrofolate (CH2-H-4-folate) and the inhibitor 5-fluoro-2'-deoxyuridylate, excited at 337 or 356 nm, in resonance with perturbed absorption bands of the p-aminobenzoylglutamate (PABA-Glu) portion of the cofactor. For comparison, RR spectra were obtained with 260 nm excitation for PABA-Glu in various solvents, and for CH2H4-folate and H-4-folate in aqueous solution. These reference spectra are assigned to modes of PABA-Glu in its benzenoid form. The ternary complex RR spectra are very different, however, and are assigned, with the aid of isotopic data, to the PABA-Glu in a predominantly quinoid form. Similar spectra were obtained for the ternary complexes of the E58Q and K48Q mutants, indicating that neither Glu58 nor Lys48 are essential for maintaining the quinoid structure, even though their side chains complement the dipolar charge distribution of the quinoid form of PABA-Glu. Since these are the only charged residues in the PABA-Glu vicinity, electrostatic stabilization is not essential to maintenance of the quinoid structure. It is proposed that quinoid formation results from steric forces, probably resulting from the protein conformation change known to accompany cofactor binding, which enforce coplanarity of the PBBA-Glu ring and substituents. This stereoelectronic change activates the cofactor by opening the methylene bridge. A second RR spectrum of the ternary complex, previously proposed to reflect an alternate structure, is shown to result instead from irreversible formation of a laser-induced photoproduct. C1 PRINCETON UNIV,DEPT CHEM,PRINCETON,NJ 08544. AGOURON PHARMACEUT INC,SAN DIEGO,CA 92121. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. FU NIGMS NIH HHS [GM25158] NR 28 TC 7 Z9 7 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 13 PY 1995 VL 34 IS 23 BP 7678 EP 7685 DI 10.1021/bi00023a014 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD333 UT WOS:A1995RD33300014 PM 7779814 ER PT J AU SCHAFER, M IMAI, Y UHL, GR STEIN, C AF SCHAFER, M IMAI, Y UHL, GR STEIN, C TI INFLAMMATION ENHANCES PERIPHERAL MU-OPIOID RECEPTOR-MEDIATED ANALGESIA, BUT NOT MU-OPIOID RECEPTOR TRANSCRIPTION IN DORSAL-ROOT GANGLIA SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ANTINOCICEPTION; MU-OPIOID RECEPTOR; DORSAL ROOT GANGLION; PRIMARY AFFERENT NEURON; RIBONUCLEASE PROTECTION ASSAY; BETA-FUNALTREXAMINE ID OPIATE RECEPTOR; SPINAL-CORD; CLONING AB mu-Opioid receptor agonist [D-Ala(2),NMe-Phe(4),Gly(5)-ol]enkephalin (DAMGO)-induced peripheral analgesic effects occur early in hindpaws inoculated with Freund's complete adjuvant and increase in parallel to the development of inflammatory signs. Antagonism of these effects by beta-funaltrexamine, an irreversible mu-opioid receptor antagonist, suggests that the effective number of peripheral opioid receptors does not increase during early stages, but does so at later stages of the inflammation. As determined by a ribonuclease protection assay, mu-opioid receptor mRNA in dorsal root ganglia is abundant in untreated animals, but does not significantly increase following inflammation. Thus, peripheral analgesic efficacy of DAMGO is not correlated with transcription or number of mu-opioid receptors at early inflammatory stages. At later stages, however, the number of peripheral mu-opioid receptors appears to increase and may enhance opioid efficacy. C1 NIDA,DIV INTRAMURAL RES,MOLEC NEUROBIOL SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT CRIT CARE MED,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. RP SCHAFER, M (reprint author), NIDA,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. FU NINDS NIH HHS [R01NS32466] NR 16 TC 99 Z9 102 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 JUN 12 PY 1995 VL 279 IS 2-3 BP 165 EP 169 DI 10.1016/0014-2999(95)00150-J PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RE213 UT WOS:A1995RE21300008 PM 7556397 ER PT J AU YAKOVLEV, GI MOISEYEV, GP PROTASEVICH, II RANJBAR, B BOCHAROV, AL KIRPICHNIKOV, MP GILLI, RM BRIAND, CM HARTLEY, RW MAKAROV, AA AF YAKOVLEV, GI MOISEYEV, GP PROTASEVICH, II RANJBAR, B BOCHAROV, AL KIRPICHNIKOV, MP GILLI, RM BRIAND, CM HARTLEY, RW MAKAROV, AA TI DISSOCIATION-CONSTANTS AND THERMAL-STABILITY OF COMPLEXES OF BACILLUS-INTERMEDIUS RNASE AND THE PROTEIN INHIBITOR OF BACILLUS-AMYLOLIQUEFACIENS RNASE SO FEBS LETTERS LA English DT Article DE BINASE BARSTAR COMPLEX; DISSOCIATION CONSTANT; HEAT DENATURATION; SCANNING MICROCALORIMETRY; ISOTHERMAL MICROCALORIMETRY ID BARNASE; BARSTAR AB Binase, the extracellular ribonuclease of Bacillus intermedias, is inhibited by barstar, the natural protein inhibitor of the homologous RNase, barnase, of B. intermedius. The dissociation constants of the binase complexes with barstar and its double Cys(40,82)Ala mutant are about 10(-12) M, only 5 to 43 times higher than those of the barnase-barstar complex. As with barnase, the denaturation temperature of binase is raised dramatically in the complex. Calorimetric studies of the formation and stability of the binase-barstar complex show that the binase reaction with barstar is qualitatively similar to that of barnase but some significant quantitative differences are reported. C1 RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. UNIV AIX MARSEILLE 2,CNRS,URA 1924,F-13385 MARSEILLE,FRANCE. NIDDKD,BETHESDA,MD 20892. RI Makarov, Alexander/P-5279-2016 NR 14 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 12 PY 1995 VL 366 IS 2-3 BP 156 EP 158 DI 10.1016/0014-5793(95)00491-Q PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RD418 UT WOS:A1995RD41800015 PM 7789535 ER PT J AU GONG, DW MORTIN, MA HORIKOSHI, M NAKATANI, Y AF GONG, DW MORTIN, MA HORIKOSHI, M NAKATANI, Y TI MOLECULAR-CLONING OF CDNA-ENCODING THE SMALL-SUBUNIT OF DROSOPHILA TRANSCRIPTION INITIATION-FACTOR TFIIF SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA POLYMERASE-II; BACTERIAL SIGMA FACTORS; PREINITIATION COMPLEX; DNA-BINDING; SEQUENCE; RAP30; RAP74; CONSERVATION; NUCLEOTIDE; XENOPUS AB Transcription initiation factor TFIIF is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30). We report here the molecular cloning of a Drosophila cDNA encoding TFIIF beta. The cDMA clone contains an open-reading frame encoding a 277 amino acid polypeptide having a calculated molecular mass of 32 107 Da. Comparison of the deduced amino acid sequence with the corresponding sequences from vertebrates showed only 50% identity, with four insertion/deletion points. For transcription activity in a TFIIF-depleted Drosophila nuclear extract, both TFIIF alpha and TFIIF beta are essential. Moreover, Drosophila TFIIF beta interacts with both Drosophila and human TFIIF alpha in vitro. Thus we conclude that isolated cDNA encodes bona fide TFIIF beta. The structural domains of TFIIF beta and its sequence similarity to bacterial sigma factors are discussed. C1 NICHHD,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,DEV BIOL LAB,BUNKYO KU,TOKYO 113,JAPAN. RI Mortin, Mark/B-4251-2008 NR 28 TC 5 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1995 VL 23 IS 11 BP 1882 EP 1886 DI 10.1093/nar/23.11.1882 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE996 UT WOS:A1995RE99600007 PM 7596813 ER PT J AU MOLLER, H MELLEMKJAER, L MCLAUGHLIN, JK OLSEN, JH AF MOLLER, H MELLEMKJAER, L MCLAUGHLIN, JK OLSEN, JH TI OCCURRENCE OF DIFFERENT CANCERS IN PATIENTS WITH PARKINSONS-DISEASE SO BRITISH MEDICAL JOURNAL LA English DT Article ID MELANOMA C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MOLLER, H (reprint author), INT AGCY RES CANC,F-69372 LYON,FRANCE. OI Moller, Henrik/0000-0001-8200-5929 NR 5 TC 66 Z9 67 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUN 10 PY 1995 VL 310 IS 6993 BP 1500 EP 1501 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RD285 UT WOS:A1995RD28500021 PM 7787596 ER PT J AU CHEN, H THALMANN, I ADAMS, JC AVRAHAM, KB COPELAND, NG JENKINS, NA BEIER, DR COREY, DP THALMANN, R DUYK, GM AF CHEN, H THALMANN, I ADAMS, JC AVRAHAM, KB COPELAND, NG JENKINS, NA BEIER, DR COREY, DP THALMANN, R DUYK, GM TI CDNA CLONING, TISSUE DISTRIBUTION, AND CHROMOSOMAL LOCALIZATION OF OCP2 A GENE ENCODING A PUTATIVE TRANSCRIPTION-ASSOCIATED FACTOR PREDOMINANTLY EXPRESSED IN THE AUDITORY ORGANS SO GENOMICS LA English DT Article ID RECOMBINANT INBRED STRAINS; MOUSE CHROMOSOME-4; LINKAGE MAP; FACTOR-SIII; PROTEINS; CORTI; REDUCTASE; SEQUENCES AB We report the cloning of the Ocp2 gene encoding OCP-II from a guinea pig organ-of-Corti cDNA library. The predicted open reading frame encodes a protein of 163 amino acids with an estimated molecular mass of 18.6 kDa. A homology search revealed that Ocp2 shares significant sequence similarity with p15, a subunit of transcription factor SIII that regulates the activity of the RNA polymerase II elongation complex. The Ocp2 messenger RNA is expressed abundantly in the cochlea while not significantly in any other tissues examined, including brain, eye, heart, intestine, kidney, liver, lung, thigh muscle, and testis, demonstrating that the expression of this gene may be restricted to auditory organs. A polyclonal antiserum was raised against the N-terminal region of OCP-II. Immunohistochemical staining of paraffin-embedded sections of the cochlea showed that OCP-II is localized abundantly in nonsensory cells in the organ of Corti; in addition, it was also detected, at a lower concentration, in vestibular sensory organs, as well as auditory and vestibular brain stem nuclei. The Ocp2 gene was mapped to mouse chromosome 4 as well as 11. Our results suggest that OCP-II may be involved in transcription regulation for the development or maintenance of specialized functions of the inner ear. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. WASHINGTON UNIV,DEPT OTOLARYNGOL,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Corey, David/0000-0003-4497-6016 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [5F32GM15909-02]; PHS HHS [R01 00269] NR 40 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 389 EP 398 DI 10.1006/geno.1995.1068 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100001 PM 7558018 ER PT J AU KOZAK, CA ADAMSON, MC BUCKLER, CE SEGOVIA, L PARALKAR, V WISTOW, G AF KOZAK, CA ADAMSON, MC BUCKLER, CE SEGOVIA, L PARALKAR, V WISTOW, G TI GENOMIC CLONING OF MOUSE MIF (MACROPHAGE INHIBITORY FACTOR) AND GENETIC-MAPPING OF THE HUMAN AND MOUSE EXPRESSED GENE AND 9 MOUSE PSEUDOGENES SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; FAMILY MEMBERS; LOCALIZATION; RECEPTOR; PROTEINS; SUBUNIT; SCRAPIE; PANEL-2; GAMMA; CELLS AB The single functional mouse gene for MIF (macrophage migration inhibitory factor) has been cloned from a P1 library, and its exon/intron structure determined and shown to resemble that of the human gene. The gene was mapped to chromosome 10 using two multilocus crosses between laboratory strains and either Mus musculus musculus or Mus spretus. Nine additional loci containing related sequences, apparently all processed pseudogenes, were also mapped to chromosomes 1, 2, 3, 7, 8, 9, 12, 17, and 19, While most of these pseudogenes were found in inbred mice and M. spretus, some are species specific. This suggests that there have been active phases of pseudogene formation in Mus both before and after the separation of musculus and spretus. The human genome contains no pseudogenes; we assigned the human gene to chromosome 19, consistent with the location of mouse and human functional genes for MIF in a region of conserved linkage. (C) 1995 Academic Press, Inc. C1 NEI,LMDB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892. RP KOZAK, CA (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. RI Segovia, Lorenzo/A-5206-2008 OI Segovia, Lorenzo/0000-0002-4291-4711 NR 43 TC 41 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 405 EP 411 DI 10.1006/geno.1995.1070 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100003 PM 7558020 ER PT J AU BOZZA, M KOLAKOWSKI, LF JENKINS, NA GILBERT, DJ COPELAND, NG DAVID, JR GERARD, C AF BOZZA, M KOLAKOWSKI, LF JENKINS, NA GILBERT, DJ COPELAND, NG DAVID, JR GERARD, C TI STRUCTURAL CHARACTERIZATION AND CHROMOSOMAL LOCATION OF THE MOUSE MACROPHAGE-MIGRATION INHIBITORY FACTOR GENE AND PSEUDOGENES SO GENOMICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; MOLECULAR-CLONING; LYMPHOCYTE MEDIATORS; LINKAGE MAP; INTERSPECIFIC BACKCROSS; LOCALIZATION; EXPRESSION; CELLS; HYPERSENSITIVITY; ORGANIZATION AB Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to integrate peripheral and central inflammatory responses. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside of the immune system. Here we report the structure and chromosomal location of the mouse Mif gene and the partial characterization of five Mif pseudogenes. The mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of three exons. A comparison between the mouse and the human genes shows a similar gene structure and common regulatory elements in both promoter regions. The mouse Mif gene maps to the middle region of chromosome 10, between Ber and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respectively. The entire sequence of two pseudogenes demonstrates the absence of introns, the presence of the 5' untranslated region of the cDNA, a 3' poly(A) tail, and the lack of sequence similarity with untranscribed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produce mutated or truncated MIF-like proteins. Phylogenetic analyses of MIF genes and pseudogenes indicate several independent genetic events that can account for multiple genomic integrations. Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. CHILDRENS HOSP,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,BETHESDA,MD 21702. FU NCI NIH HHS [N01-CO-46000]; NIAID NIH HHS [R01 AI22532] NR 46 TC 30 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 412 EP 419 DI 10.1006/geno.1995.1071 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100004 PM 7558021 ER PT J AU MIYAZAKI, S KOZAK, CA MARCHETTI, A BUTTITTA, F GALLAHAN, D CALLAHAN, R AF MIYAZAKI, S KOZAK, CA MARCHETTI, A BUTTITTA, F GALLAHAN, D CALLAHAN, R TI THE CHROMOSOMAL LOCATION OF THE MOUSE MAMMARY-TUMOR GENE INT6 AND RELATED PSEUDOGENES IN THE MOUSE GENOME SO GENOMICS LA English DT Article ID EXPRESSION; VIRUS; SEQUENCES; INTEGRATION; EVOLUTION; RECEPTOR; REGION; MICE AB The Int6 gene is a common insertion site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors, We have determined that this gene is located centromeric of the Myc protooncogene on mouse chromosome 15. In the mouse genome there are several other Int6-reactive restriction fragments that are located on mouse chromosomes 6, 11, 14, 17, and 18. Nucleotide sequence analysis of four of six of these additional Int6 fragments showed that they contain processed Int6 pseudogenes. Comparisons between the Int6 genes of the inbred mouse laboratory strains and the wild mouse species Mus spretus and Mus mus musculus indicate that some pseudogenes were present before divergence of these species and others were acquired since their separation. (C) 1995 Academic Press, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 27 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 420 EP 424 DI 10.1006/geno.1995.1072 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100005 PM 7558022 ER PT J AU BLASCO, R MOSS, B AF BLASCO, R MOSS, B TI SELECTION OF RECOMBINANT VACCINIA VIRUSES ON THE BASIS OF PLAQUE-FORMATION SO GENE LA English DT Article DE EUKARYOTIC EXPRESSION VECTOR; HOMOLOGOUS RECOMBINATION; POXVIRUS ID DOMINANT SELECTABLE MARKER; FOREIGN GENES; EXPRESSION; RESISTANCE; VECTORS AB We developed a procedure for isolation of recombinant vaccinia viruses (re-VV) based solely on plaque formation, without a requirement for specific cell lines, selective medium or special staining. The system consists of two components: (i) a mutant non-plaque-forming VV and (ii) a plasmid vector that, through homologous recombination, can simultaneously introduce a foreign gene and repair the mutation in the VV genome. The mutant VV contains a deletion of the vp37 gene, encoding a 37-kDa protein component of the viral outer envelope that is required for efficient viral spread on cell monolayers. The plasmid vector contains a functional vp37, a strong synthetic VV early/late promoter, unique restriction sites for gene insertion, and flanking segments of VV DNA for homologous recombination. Following infection and transfection of cells with the mutant VV and plasmid vector, respectively, re-VV are identified and isolated by their ability to form plaques. To evaluate the system, a re-VV that expresses the gene encoding influenza virus hemagglutinin (HA) was isolated simply by picking visible plaques. RP BLASCO, R (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Blasco, Rafael/B-5829-2016 NR 16 TC 132 Z9 132 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 9 PY 1995 VL 158 IS 2 BP 157 EP 162 DI 10.1016/0378-1119(95)00149-Z PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RF382 UT WOS:A1995RF38200001 PM 7607536 ER PT J AU DUHE, RJ RUI, H GREENWOOD, JD GARVEY, K FARRAR, WL AF DUHE, RJ RUI, H GREENWOOD, JD GARVEY, K FARRAR, WL TI CLONING OF THE GENE ENCODING RAT JAK2, A PROTEIN-TYROSINE KINASE SO GENE LA English DT Note DE NONRECEPTOR TYROSINE KINASE; JANUS KINASE; CYTOKINE RECEPTOR-RELATED; NB2 LYMPHOMA ID GAMMA SIGNAL-TRANSDUCTION; EDITING PROGRAM; LYMPHOMA-CELLS; STIMULATION; RECEPTOR AB A complete cDNA clone encoding the rat JAK2 protein tyrosine kinase was isolated from an Nb2-SP (rat pre-T lymphoma cell line) cDNA library. The nucleotide (nt) and deduced amino acid (aa) sequences for this clone were determined and an open reading frame of 3399 bp, encoding a protein of a deduced mass of 130 kDa, was found. The coding regions of the rat and murine JakZ clones share 93.4% nt identity and 97.1% aa identity, Northern analysis demonstrated that the 5-kb mRNA is highly abundant in brain and spleen, less abundant in skeletal muscle and testis, and detectable in kidney, heart, lung and liver. Translation of the rat Jak2 mRNA in rabbit reticulocytes results in a protein which is specifically immunoprecipitated by antibodies (Ab) recognizing JAK2, but not by Ab recognizing JAK1. C1 PROGRAM RESOURCES INC DYNCORP, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. RP DUHE, RJ (reprint author), NCI, FREDERICK CANC RES & DEV CTR, DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, POB B, FREDERICK, MD 21702 USA. NR 21 TC 24 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 JUN 9 PY 1995 VL 158 IS 2 BP 281 EP 285 DI 10.1016/0378-1119(95)00041-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RF382 UT WOS:A1995RF38200021 PM 7607555 ER PT J AU ALTUS, MS WOOD, CM STEWART, DA ROSKAMS, AJI FRIEDMAN, V HENDERSON, T OWENS, GA DANNER, DB JUPE, ER DELLORCO, RT MCCLUNG, JK AF ALTUS, MS WOOD, CM STEWART, DA ROSKAMS, AJI FRIEDMAN, V HENDERSON, T OWENS, GA DANNER, DB JUPE, ER DELLORCO, RT MCCLUNG, JK TI REGIONS OF EVOLUTIONARY CONSERVATION BETWEEN THE RAT AND HUMAN PROHIBITIN-ENCODING GENES SO GENE LA English DT Note DE PROMOTER; TRANSCRIPTION INITIATION; INTRON; SPLICE JUNCTION; ANTIPROLIFERATIVE; TUMOR SUPPRESSOR ID BREAST-CANCER; HETEROLOGOUS SUBUNITS; BINDING; PROTEIN; TRANSCRIPTION; EXPRESSION; PROMOTER; CHROMOSOME-17; ASSIGNMENT; MUTATIONS AB We have analyzed and compared the 5' promoter region, the intron structure and the exon-intron flanking sequences in the rat and human prohibitin-encoding genes (PHB). Comparative analysis of a 350-nt region immediately 5' to and including the first exon identifies eight highly conserved regions, four of which correspond to binding sites for known transcriptional control proteins (CCAAT box, 'SV40' site and two Sp1 sites). The promoter lacks a TATA box. Four transcription start points (tsp) clustered within a 35-bp region were identified by rapid amplification of cDNA ends (RACE). The exon-intron boundaries in rat and human are highly conserved, with identical positioning of splice junctions. PCR analysis with conserved exon primers was used to detect length variation between rat and human PHB, and length differences were observed in all of the introns. C1 OKLAHOMA MED RES FDN,NOBLE CTR BIOMED RES,OKLAHOMA CITY,OK 73104. NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. NR 23 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 9 PY 1995 VL 158 IS 2 BP 291 EP 294 DI 10.1016/0378-1119(95)00164-2 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RF382 UT WOS:A1995RF38200023 PM 7607556 ER PT J AU KOZYAVKIN, SA PUSHKIN, AV EISERLING, FA STETTER, KO LAKE, JA SLESAREV, AI AF KOZYAVKIN, SA PUSHKIN, AV EISERLING, FA STETTER, KO LAKE, JA SLESAREV, AI TI DNA ENZYMOLOGY ABOVE 100-DEGREES-C - TOPOISOMERASE V UNLINKS CIRCULAR DNA AT 80-120-DEGREES-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID EXTREMELY THERMOPHILIC ARCHAEBACTERIA; DESULFUROCOCCUS-AMYLOLYTICUS; PYROCOCCUS-FURIOSUS; ELECTRON-MICROSCOPY; POLYMERASE; ARCHAEA; TEMPERATURE; BACTERIA; AMPLIFICATION; SEQUENCES AB The widespread application of polymerase chain reaction and related techniques in biology and medicine has led to a heightened interest in thermophilic enzymes of DNA metabolism. Some of these enzymes are stable for hours at 100 degrees C, but no enzymatic activity on duplex DNA at temperatures above 100 degrees C has so far been demonstrated. Recently, we isolated topoisomerase V from the hyperthermophile Methanopyrus kandleri, which grows up to 110 degrees C. This novel enzyme is similar to eukaryotic topoisomerase I and acts on duplex DNA regions. We now show that topoisomerase V catalyzes the unlinking of double-stranded circular DNA at temperatures up to 122 degrees C. In this in vitro system, maximal DNA unlinking occurs at 108 degrees C and corresponds to complementary strands being linked at most once. These results further imply that in the presence of sufficient positive supercoiling DNA can exist as a double helix even at 122 degrees C. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV REGENSBURG,W-8400 REGENSBURG,GERMANY. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. NR 41 TC 18 Z9 19 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 9 PY 1995 VL 270 IS 23 BP 13593 EP 13595 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800004 PM 7775408 ER PT J AU LUJAN, HD MOWATT, MR WU, JJ LU, Y LEES, A CHANCE, MR NASH, TE AF LUJAN, HD MOWATT, MR WU, JJ LU, Y LEES, A CHANCE, MR NASH, TE TI PURIFICATION OF A VARIANT-SPECIFIC SURFACE PROTEIN OF GIARDIA-LAMBLIA AND CHARACTERIZATION OF ITS METAL-BINDING PROPERTIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAY ABSORPTION-SPECTROSCOPY; ANTIGENIC VARIATION; ZINC-BINDING; FINE-STRUCTURE; EXAFS; SITES; CLEAVAGE; GENE; TOOL; DNA AB Giardia lamblia, an intestinal parasite of humans and other vertebrates, undergoes surface antigenic variation by modulating the expression of different variant-specific surface proteins (VSP). VSPs are cysteine-rich surface proteins that bind zinc and other heavy metals in vitro. We developed an immunoaffinity chromatographic method to purify a VSP in order to determine its biochemical properties. The sequences of two different proteolytic fragments agreed with the sequence deduced from the cloned gene, and amino-terminal sequence indicated the removal of a 14 residue signal peptide, consistent with the transport of VSP to the cell surface, The protein is not glycosylated and has an isoelectric point of 5.3. X-ray microanalyses indicated that the major metals in Giardia trophozoites, as well as purified VSP, are zinc and iron. The zinc concentration in Giardia cells was found to be 0.43 mM and the iron concentration 0.80 mM when compared with standard samples (zinc) or calculated hom a known physical constants (iron), We propose that metal coordination stabilizes VSPs, rendering them resistant to proteolytic attack in the upper small intestine. Moreover, the ability to bind ions by Giardia may play a role in nutritional deficiency and/or malabsorption in heavily infected persons. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 45 TC 36 Z9 37 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 JUN 9 PY 1995 VL 270 IS 23 BP 13807 EP 13813 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800036 PM 7775437 ER PT J AU KIM, JH WESS, J VANRHEE, AM SCHONEBERG, T JACOBSON, KA AF KIM, JH WESS, J VANRHEE, AM SCHONEBERG, T JACOBSON, KA TI SITE-DIRECTED MUTAGENESIS IDENTIFIES RESIDUES INVOLVED IN LIGAND RECOGNITION IN THE HUMAN A(2A) ADENOSINE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; RADIOLIGAND BINDING; ADENYLATE-CYCLASE; RAT-BRAIN; EXPRESSION; CLONING; AGONIST; ACTIVATION; INHIBITION; CELLS AB The A(2a) adenosine receptor is a member of the G-protein coupled receptor family, and its activation stimulates cyclic AMP production. To determine the residues which are involved in ligand binding, several residues in transmembrane domains 5-7 were individually replaced with alanine and other amino acids, The binding properties of the resultant mutant receptors were determined in transfected COS-7 cells. To study the expression levels in COS-7 cells, mutant receptors were tagged at their amino terminus with a hemagglutinin epitope, which allowed their immunological detection in the plasma membrane by the monoclonal antibody 12CA5. The functional properties of mutant receptors were determined by measuring stimulation of adenylate cyclase. Specific binding of [H-3]CGS 21680 (15 nM) and [H-3]XAC (4 nM), an A(2a) agonist and antagonist, respectively, was absent in the following Ala mutants: F182A, H250A, N253A, I274A, H278A, and S281A, although they were well expressed in the plasma membrane. The hydroxy group of Ser-277 is required for high affinity binding of agonists, but not antagonists. An N181S mutant lost affinity for adenosine agonists substituted at N-6 or C-2, but not at C-5 '. The mutant receptors I274A, S277A, and H278A showed full stimulation of adenylate cyclase at high concentrations of CGS 21680. The functional agonist potencies at mutant receptors that lacked radioligand binding were >30-fold less than those at the wild type receptor. His-250 appears to be a required component of a hydrophobic pocket, and H-bonding to this residue is not essential. On the other hand, replacement of His-278 with other aromatic residues was not tolerated in ligand binding. Thus, some of the residues targeted in this study may be involved in the direct interaction with ligands in the human A(2a) adenosine receptor. A molecular model based on the structure of rhodopsin, in which the 5 '-NH in NECA is hydrogen bonded to Ser-277 and His-278, was developed in order to visualize the environment of the ligand binding site. C1 NIDDK,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,DRUG RECEPTOR INTERACT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 42 TC 177 Z9 179 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 9 PY 1995 VL 270 IS 23 BP 13987 EP 13997 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800060 PM 7775460 ER PT J AU DRACHEVA, S KOONIN, EV CRUTE, JJ AF DRACHEVA, S KOONIN, EV CRUTE, JJ TI IDENTIFICATION OF THE PRIMASE ACTIVE-SITE OF THE HERPES-SIMPLEX VIRUS TYPE-1 HELICASE-PRIMASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-ALPHA; PROTEIN; ALIGNMENT; REGION; EXPRESSION; SEQUENCE AB Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase-primase composed of the products of the three DNA replication-specific genes UL5, UL8, and UL52 (Crute, J. J., and Lehman, I. R. (1991) J. Biol. Chem. 266, 4484-4488). The UL5 and UL52 products constitute a heterodimeric subassembly of the holoenzyme that contains both helicase and primase activities (Calder, J. M., and Stow, N. D. (1990) Nucleic Acids Res. 18, 3573-3578; Dodson, M. S., and Lehman, I. R. (1991) Proc. Natl. Bead. Sci. U.S.A. 88, 1105-1109). The role of the UL52 product in the active HSV-1 helicase-primase was examined. A sequence located between residues 610 and 636 on the UL52 protein was found to be conserved among the UL52 homologues of eight herpesviruses. The carboxyl-terminal portion of this conserved sequence consisted of two Asp residues separated by a variable hydrophobic amino acid residue and is analogous to the divalent metal-binding site of DNA polymerases and several DNA primases. This motif has been designated the herpesvirus primase DXD motif. To study the role of the HSV-1 primase DXD motif in primase action, three site-directed changes were introduced into the UL52 gene. The helicase activity of the recombinant holoenzymes was unaffected by any of the introduced changes. Changing either of the two Asp residues that constitute the divalent metal-binding site (Asp(628) or, Asp(630)) to Ala dramatically reduced the primase activity of the HSV-1 helicase-primase holoenzyme in vitro, whereas alteration of the nearby conserved residue Asn(624) to Gly had minimal effect. Therefore, in the three-subunit HSV-1 helicase-primase, the UL52 product provides at least a part of the primase catalytic site. C1 BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT IMMUNOL DIS,RIDGEFIELD,CT 06877. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 27 TC 79 Z9 79 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 JUN 9 PY 1995 VL 270 IS 23 BP 14148 EP 14153 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800081 PM 7775476 ER PT J AU AROCA, P BOTTARO, DP ISHIBASHI, T AARONSON, SA SANTOS, E AF AROCA, P BOTTARO, DP ISHIBASHI, T AARONSON, SA SANTOS, E TI HUMAN DUAL-SPECIFICITY PHOSPHATASE VHR ACTIVATES MATURATION PROMOTION FACTOR AND TRIGGERS MEIOTIC MATURATION IN XENOPUS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; MAP KINASE; ONCOGENE PRODUCT; M-PHASE; CELL-DIVISION; RAS PROTEINS; INDUCTION; EXTRACTS; CDC25; MPF AB Bacterially expressed, dual specificity phosphatase VHR protein induced germinal vesicle breakdown (GVBD) when microinjected into Xenopus oocytes, albeit with slower kinetics than that observed in progesterone- or insulin-induced maturation, A mutant VHR protein missing an essential cysteine residue for its in vitro phosphatase activity completely lacked activity in injected oocytes, VHR injection done in conjunction with progesterone or insulin treatment resulted in highly synergized GVBD responses showing much faster kinetics than that produced by VHR or either hormone alone, The delayed kinetics of VHR-induced GVBD and the synergistic responses obtained in the presence of hormones suggested that this protein may be promoting G(2)/M transition by weakly mimicking the action of cdc25, the dual specificity phosphatase that physiologically activates the maturation promotion factor. Various experimental observations are consistent with such a role for the injected VHR in oocytes: 1) as opposed to hormone-treated oocytes, histone H1 kinase activation is not preceded by MAPK activation in the process of GVBD in VHR-injected oocytes; 2) incubation of purified VHR with highly concentrated cell-free extracts of untreated oocytes resulted in activation of histone H1 kinase activity in the lysates; 3) coinjection of VHR with activated Ras proteins resulted in synergized responses, faster than those produced by either protein alone; 4) coinjection of VHR with the purified aminoterminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (which blocks insulin-induced GVBD) does not affect VHR-induced maturation. The biological actions of VHR in oocytes clearly distinguish it from other dual specificity phosphatases, which have shown inhibitory effects when tested in oocytes, We speculate that VHR may represent a dual specificity phosphatase responsible for activation of cdk-cyclin complex(es) at a still undetermined stage of the cell cycle. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 47 TC 20 Z9 21 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 JUN 9 PY 1995 VL 270 IS 23 BP 14229 EP 14234 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800092 PM 7775484 ER PT J AU PILATTE, Y ROSTOKER, G VIOLLEAU, K BASTA, M HAMMER, CH AF PILATTE, Y ROSTOKER, G VIOLLEAU, K BASTA, M HAMMER, CH TI FURTHER IDENTIFICATION OF HUMAN PLASMA GLYCOPROTEINS INTERACTING WITH THE GALACTOSE-SPECIFIC LECTIN JACALIN SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID IGA-BINDING LECTIN; O-LINKED OLIGOSACCHARIDES; AFFINITY-CHROMATOGRAPHY; C1 INHIBITOR; PURIFICATION; AGAROSE; COMPLEMENT; PROTEIN; ASSAY AB In this report we show that Jacalin binds the heme-binding protein hemopexin and the C4b-binding protein sgp120 in human plasma. The interaction of Jacalin with hemopexin confirms that a single O-linked oligosaccharide is sufficient to mediate binding of a protein to this lectin. Retention of sgp120 by immobilized Jacalin demonstrated that this protein was O-glycosylated and, therefore, clearly different from another C4b-binding protein, the complement protein C2 which is physicochemically similar but exclusively N-glycosylated. In addition, Jacalin was also shown to bind several proteolytic enzymes which remain to be identified. C1 NIAID,LCI,BETHESDA,MD 20892. RP PILATTE, Y (reprint author), HOP HENRI MONDOR,INST MONDOR MED MOLEC,INSERM,U139,F-94010 CRETEIL,FRANCE. OI Basta, Milan/0000-0001-5958-9241 NR 28 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUN 9 PY 1995 VL 668 IS 1 BP 1 EP 11 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RD565 UT WOS:A1995RD56500001 PM 7550965 ER PT J AU CUSHMAN, M HE, HM KATZENELLENBOGEN, JA LIN, CM HAMEL, E AF CUSHMAN, M HE, HM KATZENELLENBOGEN, JA LIN, CM HAMEL, E TI SYNTHESIS, ANTITUBULIN AND ANTIMITOTIC ACTIVITY, AND CYTOTOXICITY OF ANALOGS OF 2-METHOXYESTRADIOL, AN ENDOGENOUS MAMMALIAN METABOLITE OF ESTRADIOL THAT INHIBITS TUBULIN POLYMERIZATION BY BINDING TO THE COLCHICINE BINDING-SITE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANGIOGENESIS; ESTROGENS; PROTEINS; MCF-7; CELLS AB In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low. C1 UNIV ILLINOIS,DEPT CHEM,URBANA,IL 61801. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP CUSHMAN, M (reprint author), PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [N01-CM-17512]; NIDDK NIH HHS [5R37DK15556] NR 19 TC 173 Z9 173 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 9 PY 1995 VL 38 IS 12 BP 2041 EP 2049 DI 10.1021/jm00012a003 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RC220 UT WOS:A1995RC22000003 PM 7783135 ER PT J AU MASH, DC STALEY, JK BAUMANN, MH ROTHMAN, RB HEARN, WL AF MASH, DC STALEY, JK BAUMANN, MH ROTHMAN, RB HEARN, WL TI IDENTIFICATION OF A PRIMARY METABOLITE OF IBOGAINE THAT TARGETS SEROTONIN TRANSPORTERS AND ELEVATES SEROTONIN SO LIFE SCIENCES LA English DT Letter DE 12-HYDROXYIBOGAMINE; SEROTONIN TRANSPORTERS; MICRODIALYSIS; DESMETHYL IBOGAINE ID RATS AB Ibogaine is a hallucinogenic indole with putative efficacy for the treatment of cocaine, stimulant and opiate abuse. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. We report here that 12-hydroxyibogamine, a primary metabolite of ibogaine, displays high affinity for the 5-HT transporter and elevates extracellular 5-HT. In radioligand binding assays, 12-hydroxyibogamine was 50-fold more potent at displacing radioligand binding at the 5-HT transporter than at the DA transporter. Ibogaine and 12-hydroxyibogamine were equipotent at the dopamine transporter. In vivo microdialysis was used to evaluate the acute actions of ibogaine and 12-hydroxyibogamine on the levels of DA and 5-HT. Administration of 12-hydroxyibogamine produced a marked dose-related elevation of extracellular 5-HT. Ibogaine and 12-hydroxyibogamine failed to elevate DA levels in the nucleus accumbens over the dose range tested. The elevation in synaptic levels of 5-HT by 12-hydroxyibogamine may heighten mood and attenuate drug craving. The effects of the active metabolite on 5-HT transmission may account in part for the potential of ibogaine to interrupt drug-seeking behavior in humans. C1 UNIV MIAMI,SCH MED,DEPT MOLEC & CELLULAR PHARMACOL,MIAMI,FL 33136. METRODADE CTY MED EXAMINER DEPT,MIAMI,FL 33136. NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. RP MASH, DC (reprint author), UNIV MIAMI,SCH MED,DEPT NEUROL,MIAMI,FL 33136, USA. FU NIDA NIH HHS [DA09202] NR 16 TC 32 Z9 32 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 9 PY 1995 VL 57 IS 3 BP PL45 EP PL50 DI 10.1016/0024-3205(95)00273-9 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RC378 UT WOS:A1995RC37800011 PM 7596224 ER PT J AU PHILLIPS, RS COHEN, LA ANNBY, U WENSBO, D GRONOWITZ, S AF PHILLIPS, RS COHEN, LA ANNBY, U WENSBO, D GRONOWITZ, S TI ENZYMATIC-SYNTHESIS OF THIA-L-TRYPTOPHANS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID DISEASE AB Thia analogs of L-tryptophan (beta-3-thieno[2,3-b]pyrrolyl-L-alanine and beta-3-thieno[3,2-b]pyrrolyl-L-alanine) have been prepared by the reaction of L-serine and thienopyrroles catalysed by Salmonella typhimurium tryptophan synthase. C1 UNIV GEORGIA,CTR METALLOENZYME STUDIES,ATHENS,GA 30602. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. LUND UNIV,CTR CHEM,DEPT ORGAN CHEM,S-22100 LUND,SWEDEN. RP PHILLIPS, RS (reprint author), UNIV GEORGIA,DEPT CHEM,DEPT BIOCHEM & MOLEC BIOL,ATHENS,GA 30602, USA. OI Phillips, Robert/0000-0001-8710-562X NR 7 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 8 PY 1995 VL 5 IS 11 BP 1133 EP 1134 DI 10.1016/0960-894X(95)00181-R PG 2 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA RD673 UT WOS:A1995RD67300006 ER PT J AU PODGORNIK, R PARSEGIAN, VA AF PODGORNIK, R PARSEGIAN, VA TI FORCES BETWEEN CTAB-COVERED GLASS SURFACES INTERPRETED AS AN INTERACTION-DRIVEN SURFACE INSTABILITY SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID CETYLTRIMETHYLAMMONIUM BROMIDE; HYDROPHOBIC SURFACES; MICA; ADSORPTION; MICROSCOPY AB We examine recently reported forces between glass surfaces immersed in solutions of an adsorbing charged amphiphile (CTAB). The collapse of electrostatic double layer repulsion in such systems had been the occasion for suspecting the existence of hydrophobic attraction at surprisingly large, similar to 10 nm, separations. Now, following the reasoning of a surface-instability model of ''hydrophobic'' interactions, we combine the Derjaguin approximation for the interaction of oppositely curved surfaces with general thermodynamic Maxwell relations and Gibbs adsorption isotherms. This combination creates a procedure to analyze chemically sensitive forces between macroscopic surfaces while explicitly including the chemical potentials of adsorbing species. At least in this system where solution conditions are specified, puzzling long-range attractive forces turn out either to be the consequence of an instability in the amount of adsorbed CTAB, driven by the changes in the intersurface separation, or to be a simple van der Waals force between surfaces whose separations are diminished by layers of adsorbed amphiphile. There appears to be no need in this case to assume the existence of more abstruse mechanisms. C1 NCI,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 22 TC 38 Z9 38 U1 3 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUN 8 PY 1995 VL 99 IS 23 BP 9491 EP 9496 DI 10.1021/j100023a029 PG 6 WC Chemistry, Physical SC Chemistry GA RC459 UT WOS:A1995RC45900029 ER PT J AU RUBINOW, DR SCHMIDT, PJ AF RUBINOW, DR SCHMIDT, PJ TI THE TREATMENT OF PREMENSTRUAL-SYNDROME - FORWARD INTO THE PAST SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MODULATION RP RUBINOW, DR (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 14 TC 25 Z9 25 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 JUN 8 PY 1995 VL 332 IS 23 BP 1574 EP 1575 DI 10.1056/NEJM199506083322309 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RB196 UT WOS:A1995RB19600009 PM 7739713 ER PT J AU LINDBERG, DAB HUMPHREYS, BL AF LINDBERG, DAB HUMPHREYS, BL TI COMPUTERS IN MEDICINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LIBRARY RP LINDBERG, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 16 TC 31 Z9 31 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 JUN 7 PY 1995 VL 273 IS 21 BP 1667 EP 1668 DI 10.1001/jama.273.21.1667 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RB097 UT WOS:A1995RB09700015 PM 7752407 ER PT J AU FREIFELD, A PIZZO, P AF FREIFELD, A PIZZO, P TI COLONY-STIMULATING FACTORS AND NEUTROPENIA - INTERSECTION OF DATA AND CLINICAL RELEVANCE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CANCER; FEVER; CHEMOTHERAPY; EPISODES C1 NCI,DIV CANC TREATMENT,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 16 TC 7 Z9 7 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 JUN 7 PY 1995 VL 87 IS 11 BP 781 EP 782 DI 10.1093/jnci/87.11.781 PG 2 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300002 PM 7791222 ER PT J AU BOSCH, FX MANOS, MM MUNOZ, N SHERMAN, M JANSEN, AM PETO, J SCHIFFMAN, MH MORENO, V KURMAN, R SHAH, KV ALIHONOU, E BAYO, S MOKHTAR, HC CHICAREON, S DAUDT, A DELOSRIOS, E GHADIRIAN, P KITINYA, JN KOULIBALY, M NGELANGEL, C TINTORE, LMP RIOSDALENZ, JL SARJADI SCHNEIDER, A TAFUR, L TEYSSIE, AR ROLON, PA TORROELLA, M TAPIA, AV WABINGA, HR ZATONSKI, W SYLLA, B VIZCAINO, P MAGNIN, D KALDOR, J GREER, C WHEELER, C AF BOSCH, FX MANOS, MM MUNOZ, N SHERMAN, M JANSEN, AM PETO, J SCHIFFMAN, MH MORENO, V KURMAN, R SHAH, KV ALIHONOU, E BAYO, S MOKHTAR, HC CHICAREON, S DAUDT, A DELOSRIOS, E GHADIRIAN, P KITINYA, JN KOULIBALY, M NGELANGEL, C TINTORE, LMP RIOSDALENZ, JL SARJADI SCHNEIDER, A TAFUR, L TEYSSIE, AR ROLON, PA TORROELLA, M TAPIA, AV WABINGA, HR ZATONSKI, W SYLLA, B VIZCAINO, P MAGNIN, D KALDOR, J GREER, C WHEELER, C TI PREVALENCE OF HUMAN PAPILLOMAVIRUS IN CERVICAL-CANCER - A WORLDWIDE PERSPECTIVE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; NEW-MEXICO; INFECTION; WOMEN; DETERMINANTS; RISK; CARCINOMA; COLOMBIA; GRADE-3; SPAIN AB Background: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. Purpose: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. Methods: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. Results: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries, HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%, HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common, There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America, In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors), Conclusions: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. Implication: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs. C1 CSUB, HOSP DURAN I REYNAL, INST CATALA ONCOL, SERV EPIDEMIOL, E-08907 LHOSPITALET DE LLOBREGAT, SPAIN. CSUB, HOSP DURAN I REYNAL, INST CATALA ONCOL, REGISTRE CANC, E-08907 LHOSPITALET DE LLOBREGAT, SPAIN. JOHNS HOPKINS UNIV, SCH PUBL HLTH, DEPT MOLEC MICROBIOL & IMMUNOL, BALTIMORE, MD USA. JOHNS HOPKINS MED INST, DEPT PATHOL, BALTIMORE, MD 21205 USA. INST CANC RES, BELMONT, SURREY, ENGLAND. NCI, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. UNIV NATL BENIN, COTONON, BENIN. INST NATL RECH SANTE PUBL, BAMAKO, MALI. CHU SETIF, SETIF, ALGERIA. PRINCE SONGKLA UNIV, HAT YAI, THAILAND. HOSP CLIN PORTO ALEGRE, PORTO ALEGRE, RS, BRAZIL. NATL ONCOL INST, PANAMA CITY, PANAMA. HOP HOTEL DIEU, MONTREAL, PQ, CANADA. MUHIMBILI MED CTR, DAR ES SALAAM, TANZANIA. CTR NATL ANAT PATHOL, CONAKRY, GUINEA BISSAU. UNIV PHILIPPINES, MANILA, PHILIPPINES. HOSP CLIN BARCELONA, BARCELONA, SPAIN. CANC REGISTRY LA PAZ, LA PAZ, BOLIVIA. DIPONEGORO UNIV, FAC MED, SEMARANG, INDONESIA. UNIV JENA, JENA, GERMANY. UNIV VALLE, CALI, COLOMBIA. NATL INST MICROBIOL, BUENOS AIRES, DF, ARGENTINA. REGISTRO NACL PATOL TUMORAL, ASUNCION, PARAGUAY. NCI, HAVANA, CUBA. MINIST HLTH, HOSP CLIN REG CONCEPCION, CONCEPCION, CHILE. MAKERERE MED SCH, KAMPALA, UGANDA. M SKLODOWSKA CURIE MEM CANC CTR, WARSAW, POLAND. NATL CTR HIV EPIDEMIOL & CLIN RES, DARLINGHURST, NSW, AUSTRALIA. CHIRON CORP, EMERYVILLE, CA USA. UNIV NEW MEXICO, ALBUQUERQUE, NM USA. RI Moreno, Victor/A-1697-2010; Kaldor, John /D-4545-2011; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI Moreno, Victor/0000-0002-2818-5487; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 FU PHS HHS [MA5623-41] NR 30 TC 2314 Z9 2446 U1 25 U2 202 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 7 PY 1995 VL 87 IS 11 BP 796 EP 802 DI 10.1093/jnci/87.11.796 PG 7 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300009 PM 7791229 ER PT J AU LUBIN, JH BOICE, JD EDLING, C HORNUNG, RW HOWE, GR KUNZ, E KUSIAK, RA MORRISON, HI RADFORD, EP SAMET, JM TIRMARCHE, M WOODWARD, A YAO, SX PIERCE, DA AF LUBIN, JH BOICE, JD EDLING, C HORNUNG, RW HOWE, GR KUNZ, E KUSIAK, RA MORRISON, HI RADFORD, EP SAMET, JM TIRMARCHE, M WOODWARD, A YAO, SX PIERCE, DA TI LUNG-CANCER IN RADON-EXPOSED MINERS AND ESTIMATION OF RISK FROM INDOOR EXPOSURE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID URANIUM MINERS; DAUGHTER EXPOSURES; MORTALITY 1950-80; TIN MINERS; COHORT; WORKERS; STATES; PROGENY; CHINA AB Background: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. Purpose: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. Methods: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65 000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. Results: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). Conclusions: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners. C1 UPPSALA UNIV,DEPT OCCUPAT MED,UPPSALA,SWEDEN. NIOSH,CINCINNATI,OH. UNIV TORONTO,NATL CANC INST CANADA,EPIDEMIOL UNIT,TORONTO,ON,CANADA. NATL INST PUBL HLTH,CTR RADIAT HYG,PRAGUE,CZECH REPUBLIC. ONTARIO MINIST LABOR,RES & REGULAT BRANCH,HLTH & SAFETY UNIT,TORONTO,ON,CANADA. HLTH & WELF CANADA,DIV SURVEILLANCE & RISK ASSESSMENT,OTTAWA,ON,CANADA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. INST PROTECT & NUCL SAFETY,EPIDEMIOL & HLTH DETRIMENT ANAL LAB,FONTENAY ROSES,FRANCE. UNIV ADELAIDE,DEPT COMMUNITY MED,ADELAIDE,SA,AUSTRALIA. CHINA NATL NONFERROUS METALS IND CORP,YUNNAN TIN CORP,INST LABOR PROTECT,GEJIU,PEOPLES R CHINA. UNIV OREGON,DEPT STAT,CORVALLIS,OR. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RI Banks, Tamara/G-3007-2012; OI Woodward, Alistair/0000-0001-5425-6018 FU NCI NIH HHS [R01CA51007] NR 37 TC 199 Z9 210 U1 7 U2 32 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 JUN 7 PY 1995 VL 87 IS 11 BP 817 EP 827 DI 10.1093/jnci/87.11.817 PG 11 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300012 PM 7791231 ER PT J AU BRINTON, LA DALING, JR LIFF, JM SCHOENBERG, JB MALONE, KE STANFORD, JL COATES, RJ GAMMON, MD HANSON, L HOOVER, RN AF BRINTON, LA DALING, JR LIFF, JM SCHOENBERG, JB MALONE, KE STANFORD, JL COATES, RJ GAMMON, MD HANSON, L HOOVER, RN TI ORAL-CONTRACEPTIVES AND BREAST-CANCER RISK AMONG YOUNGER WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FINAL REPORT; HISTORIES; SWEDEN; AGREEMENT; NORWAY; AGE AB Background: Several studies have suggested a link between oral contraceptive use and breast cancer in younger women, but it is possible that chance or bias, including selective screening of contraceptive users, contributed to the putative association. Purpose: Given that oral contraceptives were first marketed in the United States in the early 1960s, we conducted a population-based case-control study to examine the relationship between use of oral contraceptives and breast cancer among women in a recently assembled cohort, focusing on women younger than 45 years of age who had the opportunity for exposure throughout their entire reproductive years. Methods: Breast cancer patients and healthy control subjects were identified, the latter group by random-digit dialing, in Atlanta, Ga., Seattle/Puget Sound, Wash., and central New Jersey, In Seattle and New Jersey, the study was confined to women 20 through 44 years of age; in Atlanta the age range was extended through 54 years, Patients included women with in situ or invasive breast cancer newly diagnosed during the period of May 1, 1990, through December 31, 1992. In-person interviews were completed by 2203 (86.4%) of 2551 eligible patients and 2009 (78.1%) of 2571 eligible control subjects. Analyses focused on women younger than 45 years of age (1648 patients acid 1505 control subjects) to maximize opportunities for extended exposure. Logistic regression analyses were used to obtain maximum likelihood estimates of relative risks (RRs) and their 95% confidence intervals (CIs). Results: Among women younger than 45 years, oral contraceptive use for 6 months or longer was associated with an RR for breast cancer of 1.3 (95% CI = 1.1-1.5). Risks were enhanced for breast cancers occurring prior to age 35 years (RR = 1.7; 95% CI = 1.2-2.6), with the RR rising to 2.2 (95% CI = 1.2-4.1) for users of 10 or more years. The RR for breast cancer for those whose oral contraceptive use began early (before age 18 years) and continued long-term (>10 years) was even higher (RR = 3.1; 95% CI = 1.4-6.7). The RRs observed for those who used oral contraceptives within 5 years of cancer diagnosis were higher than for those who had not, with the effect most marked for women younger than age 35 years (RR = 2.0; 95% CI = 1.3-3.1). Oral contraceptive associations were also strongest for cancers diagnosed at advanced stages. Evaluation of screening histories and methods of diagnosis failed to support the speculation that associations could be due to selective screening. Among women 45 years of age and older, no associations of risk with use of oral contraceptives were noted. Conclusions: The relationship between oral contraceptives and breast cancer in young women appears to have a biologic basis rather than to be an artifact or the result of bias. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,ATLANTA,GA. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. WESTAT CORP,ROCKVILLE,MD. RP BRINTON, LA (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXEC PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 40 TC 138 Z9 138 U1 1 U2 6 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 JUN 7 PY 1995 VL 87 IS 11 BP 827 EP 835 DI 10.1093/jnci/87.11.827 PG 9 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300013 PM 7791232 ER PT J AU SHIELDS, PG XU, GX BLOT, WJ FRAUMENI, JF TRIVERS, GE PELLIZZARI, ED QU, YH GAO, YT HARRIS, CC AF SHIELDS, PG XU, GX BLOT, WJ FRAUMENI, JF TRIVERS, GE PELLIZZARI, ED QU, YH GAO, YT HARRIS, CC TI MUTAGENS FROM HEATED CHINESE AND US COOKING OILS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LUNG-CANCER; SPECIES-DIFFERENCES; B6C3F1 MICE; 1,3-BUTADIENE; CARCINOGENICITY; WORKERS; FORMALDEHYDE; BUTADIENE; MORTALITY; EXPOSURE AB Background: The lung cancer incidence in Chinese women is among the highest in the world, but tobacco smoking accounts for only a minority of the cancers. Epidemiologic investigations of lung cancer among Chinese women have implicated exposure to indoor air pollution from wok cooking, where the volatile emissions from unrefined cooking oils are mutagenic. Purpose: This study was conducted to identify and quantify the potentially mutagenic substances emitted from a variety of cooking oils heated to the temperatures typically used in wok cooking. Methods: Several cooking oils and fatty acids were heated in a wok to boiling, at temperatures (for the cooking oils) that ranged from 240 degrees C to 280 degrees C (typical cooking temperatures in Shanghai, China). The oils tested were unrefined Chinese rapeseed, refined U.S. rapeseed (known as canola). Chinese soybean, and Chinese peanut in addition to linolenic, linoleic, and erucic fatty acids. Condensates of the emissions were collected and tested in the Salmonella mutation assay (using Salmonella typhimurium tester strains TA98 and TA104). Volatile decomposition products also were subjected to gas chromatography and mass spectroscopy. Aldehydes were detected using high-performance liquid chromatography and UV spectroscopy. Results: 1,3-Butadiene, benzene, acrolein, formaldehyde, and other related compounds were qualitatively and quantitatively detected, with emissions tending to be highest for unrefined Chinese rapeseed oil and lowest for peanut oil. The emission of 1,3-butadiene and benzene was approximately 22-fold and 12-fold higher, respectively, from heated unrefined Chinese rapeseed oil than from heated peanut oil. Lowering the cooking temperatures or adding an antioxidant, such as butylated hydroxyanisole, before cooking decreased the amount of these volatile emissions. Among the individual fatty acids tested, heated linolenic acid produced the greatest quantities of 1,3-butadiene, benzene, and acrolein. Separately, the mutagenicity of individual volatile emission condensates was correlated with linolenic acid content (r = .83; P = .0004). Condensates from heated linolenic acid, but not linoleic or erucic acid, were highly mutagenic. Conclusions: These studies, combined with experimental and epidemiologic findings, suggest that high-temperature wok cooking with unrefined Chinese rapeseed oil may increase lung cancer risk. This study indicates methods that may reduce that risk, Implications: The common use of wok cooking in China might be an important but controllable risk factor in the etiology of lung cancer. In the United States, where cooking oils are usually refined for purity, additional studies should be conducted to further quantify the potential risks of such methods of cooking. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. SHANGHAI CANC INST,SHANGHAI,PEOPLES R CHINA. RES TRIANGLE INST,RES TRIANGLE PK,NC. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Shields, Peter/I-1644-2012 NR 43 TC 99 Z9 108 U1 3 U2 12 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 JUN 7 PY 1995 VL 87 IS 11 BP 836 EP 841 DI 10.1093/jnci/87.11.836 PG 6 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300014 PM 7791233 ER PT J AU BROWN, LM HOOVER, RN FRAUMENI, JF AF BROWN, LM HOOVER, RN FRAUMENI, JF TI ADENOCARCINOMA OF THE ESOPHAGUS - ROLE OF OBESITY AND DIET - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 2 TC 4 Z9 4 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 7 PY 1995 VL 87 IS 11 BP 848 EP 848 DI 10.1093/jnci/87.11.848-a PG 1 WC Oncology SC Oncology GA RA843 UT WOS:A1995RA84300020 ER PT J AU HIROSE, T APFEL, R PFAHL, M JETTEN, AM AF HIROSE, T APFEL, R PFAHL, M JETTEN, AM TI THE ORPHAN RECEPTOR TAK1 ACTS AS A REPRESSOR OF RAR-MEDIATED, RXR-MEDIATED AND T3R-MEDIATED SIGNALING PATHWAYS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOIC ACID RECEPTOR; THYROID-HORMONE; RESPONSIVE ELEMENT; BETA-GENE; BINDING; PROMOTER; GROWTH AB Recently, we reported the cloning and characterization of the novel orphan receptor TAK1. In this study, we analyze the interaction of TAK1 with a variety of response elements (RE's) and demonstrate that TAK1 binds effectively to RE's composed of the core motif PuGGTCA configured in direct repeats spaced by one or more nucleotides, TAK1 bound poorly to palindromic or inverted palindromic motifs and was unable to bind to a single core motif, suggesting that a dimeric site is required for binding. Transfection experiments with CV-1 cells revealed that TAK1 is able to repress retinoid- and thyroid- hormone-induced transactivation through a subset of retinoid and thyroid hormone RE's. Our studies indicate that the antagonism of RAR-mediated transactivation does not involve the formation of heterodimers between TAK1 and RAR or RXR but is due to the competition of TAK1 homodimers with RAR-RXR heterodimers and RXR homodimers for binding to RARE and RXRE, respectively. Our results suggest that the orphan receptor TAK1 can be a negative modulator of the regulation of gene expression mediated by retinoid and thyroid hormone signaling pathways. (C) 1995 Academic Press, Inc. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. SAN DIEGO REG CANC CTR,LA JOLLA,CA 92037. RI Hirose, Takahisa /E-6117-2011 NR 26 TC 37 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 6 PY 1995 VL 211 IS 1 BP 83 EP 91 DI 10.1006/bbrc.1995.1781 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RB850 UT WOS:A1995RB85000013 PM 7779113 ER PT J AU CAWLEY, NX WONG, M PU, LP TAM, W LOH, YP AF CAWLEY, NX WONG, M PU, LP TAM, W LOH, YP TI SECRETION OF YEAST ASPARTIC PROTEASE-3 IS REGULATED BY ITS CARBOXY-TERMINAL TAIL - CHARACTERIZATION OF SECRETED YAP3P SO BIOCHEMISTRY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; SACCHAROMYCES-CEREVISIAE; ALPHA-FACTOR; GENE; ENDOPEPTIDASE; PURIFICATION; PROHORMONES; PEPTIDE; MEMBER; FAMILY AB Yeast aspartic protease 3 (YAP3p), a basic-residue specific proprotein processing enzyme, was shown to be a membrane-associated protease. The membrane association of YAP3p was demonstrated to be through a glycophosphatidylinositol anchor situated in the carboxy terminus of the enzyme. Carboxyterminal truncation of YAP3p by 37 amino acids resulted in secretion of YAP3p into the growth medium. Western blot analysis after sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed two secreted forms of YAP3p with apparent molecular masses of similar to 180 and similar to 90 kDa. YAP3p has an isoelectric point of similar to 4.5 as determined by isoelectric focusing gel electrophoresis. Treatment of YAP3p with endoglycosidase H reduced the size of both forms of the protein to similar to 65 kDa, consistent with the presence of 10 potential N-linked glycosylation sites in the deduced amino acid sequence of this protein. Removal of the N-linked sugars did not affect the enzymatic activity of YAP3p. Analysis of the effect of temperature on the stability and the rate of enzymatic activity of YAP3p showed that the enzyme retained 100% of its activity when incubated for 1 h at 37 degrees C, while incubation at 50 OC for 1 h resulted in similar to 80% loss of activity. The dependence of activity on temperature demonstrated a calculated Q(10) of 1.95. C1 NICHHD, DEV NEUROBIOL LAB, CELLULAR NEUROBIOL SECT, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT BIOCHEM, BETHESDA, MD 20814 USA. NR 30 TC 23 Z9 24 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 6 PY 1995 VL 34 IS 22 BP 7430 EP 7437 DI 10.1021/bi00022a016 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC789 UT WOS:A1995RC78900016 PM 7779785 ER PT J AU BUCKLEY, NE SY, Y MILSTIEN, S SPIEGEL, S AF BUCKLEY, NE SY, Y MILSTIEN, S SPIEGEL, S TI THE ROLE OF CALCIUM INFLUX IN CELLULAR PROLIFERATION INDUCED BY INTERACTION OF ENDOGENOUS GANGLIOSIDE GM1 WITH THE B-SUBUNIT OF CHOLERA-TOXIN SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE CALCIUM INFLUX; GANGLIOSIDE GM1; CELLULAR PROLIFERATION ID EPIDERMAL GROWTH-FACTOR; SWISS 3T3 FIBROBLASTS; PROTEIN-KINASE-C; GTP-BINDING PROTEIN; INDUCED MITOGENESIS; RECEPTOR; TRANSCRIPTION; INVOLVEMENT; ACTIVATION; CELLS AB The B subunit of cholera toxin, which binds specifically to ganglioside GM1, is mitogenic for quiescent Swiss 3T3 fibroblasts. It was previously shown that the B subunit had no effect on cAMP, protein kinase C or phosphoinositide turnover, but did cause an increase in the influx of calcium from extracellular sources (Spiegel, S. and Panagiotopoulos, C. (1988) Exp. Cell Res. 177, 414-427). In contrast to the action of known growth factors, the B subunit induced significant DNA synthesis after only a 1-3 h treatment. We utilized this unique property to determine whether the increase in calcium influx plays a role in B subunit-induced mitogenicity. Cells were briefly treated with the B subunit in the presence of calcium channel blockers, followed by removal of the blockers and further incubation in B subunit-free medium for the remaining time required to measure DNA synthesis. When 1 mM cobalt was only present during the first 3 h incubation, DNA synthesis induced by either the B subunit or fetal bovine serum was completely abolished. However, both nickel (1 mM) and the L-type voltage-gated calcium channel inhibitor nicardipin (10 mu M) inhibited B subunit-induced cell proliferation without abrogating the response to fetal bovine serum. Using a gel retardation assay, we found that the B subunit markedly stimulated specific DNA-binding activity of the transcription factor, activator protein-1 (AP-1), which functions as a major convergence point coupling early events induced by a variety of mitogens to long term growth responses. Presence of c-Fos protein in the AP-1 complex was demonstrated as a supershift band in the gel mobility assay using c-Fos polyclonal antibody. Cobalt, which markedly inhibited B subunit-induced DNA synthesis, also completely abolished AP-1 DNA-binding activity stimulated by the B subunit. In sharp contrast, cobalt had no effect on DNA-binding activity of AP-1 induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Our results suggest that calcium influx is a key element for both DNA-binding activity of AP-1 and cell proliferation induced by binding of the B subunit of cholera toxin to cell surface ganglioside GM1. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 39718] NR 38 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD JUN 6 PY 1995 VL 1256 IS 3 BP 275 EP 283 DI 10.1016/0005-2760(95)00030-G PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RC983 UT WOS:A1995RC98300002 PM 7786888 ER PT J AU BOWEN, WD VILNER, BJ WILLIAMS, W BERTHA, CM KUEHNE, ME JACOBSON, AE AF BOWEN, WD VILNER, BJ WILLIAMS, W BERTHA, CM KUEHNE, ME JACOBSON, AE TI IBOGAINE AND ITS CONGENERS ARE SIGMA(2) RECEPTOR-SELECTIVE LIGANDS WITH MODERATE AFFINITY SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE SIGMA RECEPTOR; IBOGAINE; (SUBTYPE SELECTIVITY) ID HARMALINE AB Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma(2) sites (K-i = 201 nM) and low affinity for a, sites (K-i = 8554 nM), thus showing 43-fold selectivity for sigma(2) receptors. Tabernanthine (13-methoxyibogamine) and(+/-)-ibogamine had sigma(2) K-i = 194 nM and 137 nM, respectively. However, they showed 3- to 5-fold higher sigma(1) affinity compared to ibogaine, resulting in about 14-fold selectivity for sigma(2) sites over sigma(1). A potential ibogaine metabolite, O-des-methyl-ibogaine, had markedly reduced sigma(2) affinity relative to ibogaine (K-i = 5,226 nM) and also lacked significant affinity for sigma(1) sites. (+/-)-Coronaridine ((+/-)-18-carbomethoxyibogamine) and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) lacked significant affinity for either a subtype. Thus, sigma(2) receptors could play a role in the actions of ibogaine. C1 UNIV VERMONT,DEPT CHEM,BURLINGTON,VT 05405. RP BOWEN, WD (reprint author), NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BLDG 8,RM B1-23,8 CTR DR MSC 0815,BETHESDA,MD 20892, USA. NR 8 TC 54 Z9 56 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 JUN 6 PY 1995 VL 279 IS 1 BP R1 EP R3 DI 10.1016/0014-2999(95)00247-I PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RD872 UT WOS:A1995RD87200015 PM 7556375 ER PT J AU NAKANISHI, S CATT, KJ BALLA, T AF NAKANISHI, S CATT, KJ BALLA, T TI A WORTMANNIN-SENSITIVE PHOSPHATIDYLINOSITOL 4-KINASE THAT REGULATES HORMONE-SENSITIVE POOLS OF INOSITOLPHOSPHOLIPIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADRENAL GLOMERULOSA CELLS; MULTIPLE METABOLIC POOLS; 3-KINASE; YEAST; PHOSPHOINOSITIDES; 4,5-BISPHOSPHATE; PURIFICATION; 4-PHOSPHATE; PLATELETS; KINASES AB The synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2], the immediate precursor of intracellular signals generated by calcium mobilizing hormones and growth factors, is initiated by the conversion of phosphatidylinositol to phosphatidylinositol 4-phosphate [PtdIns(4)P] by phosphatidylinositol 4-kinase (PtdIns 4-kinase), Although cells contain several PtdIns 4-kinases, the enzyme responsible for regulating the synthesis of hormone-sensitive PtdIns(4,5)P-2 pools has not been identified, In this report we describe the inhibitory effect of micromolar con centrations of wortmannin (WT) on the synthesis of hormone-sensitive PtdIns(4)P and PtdIns(4,5)P-2 pools in intact adrenal glomerulosa cells, and the presence of a WT- sensitive PtdIns 4-kinase in adrenocortical extracts, In addition to its sensitivity to the PtdIns 3 kinase inhibitor WT, this enzyme is distinguished from the recognized membrane-bound PtdIns 4-kinases by its molecular size and weak membrane association, Inhibition of this PtdIns 4 kinase by WT results in rapid loss of the hormone-sensitive PtdIns(4,5)Pz pool in angiotensin II-stimulated glomerulosa cells, Consequently, WT treatment inhibits the sustained but not the initial increases in inositol 1,4,5 trisphosphate and cytoplasmic [Ca2+] in a variety of agonist-stimulated cells, including adrenal glomerulosa cells, NIH 3T3 fibroblasts, and Jurkat lymphoblasts. These results indicate that a specific WT-sensitive PtdIns 4-kinase is critical for the maintenance of the agonist-sensitive polyphosphoinositide pool in several cell types, C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 37 TC 286 Z9 291 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 6 PY 1995 VL 92 IS 12 BP 5317 EP 5321 DI 10.1073/pnas.92.12.5317 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400013 PM 7777504 ER PT J AU NEURATH, MF MAX, EE STROBER, W AF NEURATH, MF MAX, EE STROBER, W TI PAX5 (BSAP) REGULATES THE MURINE IMMUNOGLOBULIN 3'ALPHA ENHANCER BY SUPPRESSING BINDING OF NF-ALPHA-P, A PROTEIN THAT CONTROLS HEAVY-CHAIN TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-CELL DIFFERENTIATION; LIGATION-MEDIATED PCR; SWITCH REGIONS; GENE; PROMOTER; ELEMENT; DOMAIN; SITES; LOCUS AB The Pad transcription factor BSAP (B-cell-specific activator protein) is known to bind to and repress the activity of the immunoglobulin heavy chain 3'alpha enhancer, We have detected an element-designated alpha P-that lies approximate to 50 bp downstream of the BSAP binding site 1 and is required for maximal enhancer activity, In vitro binding experiments suggest that the 40-kDa protein that binds to this element (NF-alpha P) is a member of the Ets family present in both B-cell and plasma-cell nuclei. However, in Five footprint analysis suggests that the alpha P site is occupied only in plasma cells, whereas the BSAP site is occupied in B cells but not in plasma cells. When Pax5 binding to the enhancer in B cells Has blocked in vivo by transfection with a triple-helix-forming oligonucleotide, an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased, The tripie-helix-forming oligonucleotide also increased enhancer activity of a transfected construct in B cells, but only when the alpha P Site was intact. Pax5 thus regulates the 3'alpha enhancer and immunoglobulin gene transcription by blocking activation by NF-alpha P. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 28 TC 84 Z9 84 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 JUN 6 PY 1995 VL 92 IS 12 BP 5336 EP 5340 DI 10.1073/pnas.92.12.5336 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400017 PM 7777508 ER PT J AU PORTER, JC IJAMES, CF WANG, TCL MARKEY, SP AF PORTER, JC IJAMES, CF WANG, TCL MARKEY, SP TI PURIFICATION AND IDENTIFICATION OF PITUITARY CYTOTROPIC FACTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADENOSINE; DOPAMINE ID TYROSINE-HYDROXYLASE; MEDIAN-EMINENCE; RAT-BRAIN; CELLS; HYPOTHALAMUS; EXPRESSION; NEURONS AB It has been shown that the pituitary contains a cytotropic factor (CTF) that stimulates the secretion of catecholamines by dopaminergic neurons of the hypothalamus, In the present study, CTF was purified from rat pituitaries and found by means of mass spectrometric analysis to be adenosine. This finding was corroborated by the observations that CTF behaves identically to adenosine when subjected to liquid chromatography, is inactivated and converted to inosine by adenosine deaminase, and is qualitatively and quantitatively indistinguishable from adenosine in its biological activity. It is concluded that pituitary adenosine is a trophic factor for hypothalamic dopaminergic neurons. C1 UNIV TEXAS,SW MED CTR,DEPT PHYSIOL,DALLAS,TX 75235. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP PORTER, JC (reprint author), UNIV TEXAS,SW MED CTR,DEPT OBSTET & GYNECOL,DALLAS,TX 75235, USA. FU NIA NIH HHS [5 R37 AGO4344] NR 12 TC 10 Z9 10 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 JUN 6 PY 1995 VL 92 IS 12 BP 5351 EP 5355 DI 10.1073/pnas.92.12.5351 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400020 PM 7777510 ER PT J AU MARTIN, RG ROSNER, JL AF MARTIN, RG ROSNER, JL TI BINDING OF PURIFIED MULTIPLE ANTIBIOTIC-RESISTANCE REPRESSOR PROTEIN (MARR) TO MAR OPERATOR SEQUENCES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ESCHERICHIA COLI; GENE REGULATION; SALICYLATES; DNA-PROTEIN INTERACTIONS ID ESCHERICHIA-COLI; LOCUS; SALICYLATE; INDUCTION AB Elevated expression of the marORAB multiple antibiotic-resistance operon enhances the resistance of Escherichia coli to various medically significant antibiotics, Transcription of the operon is repressed in vivo by the marR-encoded protein. MarR, and derepressed by salicylate and certain antibiotics, The possibility that repression results from MarR interacting with the marO operator-promoter region was studied in vitro using purified MarR and a DNA fragment containing marO. MarR formed at least two complexes with marO DNA bound >30-fold more tightly to it than to salmon sperm DNA, and protected two separate 21-bp sites within marO from digestion by DNase I. Site I abuts the downstream side of the putative -35 transcription-start signal and includes 4 bp of the -10 signal, Site II begins 13 bp downstream of site I, ending immediately before the first base pair of marR. Site Il, approximate to 80% homologous to site I, is not required for repression since a site II-deleted mutant (mar0133) was repressed in trans by wild-type MarR, The absence of site II did not prevent MarR from complexing with the site I of mar0133. Salicylate bound to MarR (K-d approximate to 0.5 mM) and weakened the interaction of MarR with sites I and II, Thus, repression of the mar operon, which curbs the antibiotic resistance of E. coli, correlates with the formation of MarR-site I complexes. Salicylate appears to induce the mar operon by binding to MarR and inhibiting complex formation, whereas tetracycline and chloramphenicol which neither bind MarR nor inhibit complex formation, must induce by an indirect mechanism. RP MARTIN, RG (reprint author), NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 22 TC 170 Z9 171 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 6 PY 1995 VL 92 IS 12 BP 5456 EP 5460 DI 10.1073/pnas.92.12.5456 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400041 PM 7777530 ER PT J AU ZHANG, SD ODENWALD, WF AF ZHANG, SD ODENWALD, WF TI MISEXPRESSION OF THE WHITE (w) GENE TRIGGERS MALE-MADE COURTSHIP IN DROSOPHILA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTIONAL-ANALYSIS; MELANOGASTER; LOCUS; EXPRESSION; SEQUENCE; TRANSCRIPTION; ELEMENTS; BEHAVIOR; MUTANTS AB We report here that the general ectopic expression of a tryptophan/guanine transmembrane transporter gene, white (w), induces male-male courtship in Drosophila. Activation of a hsp-70/miniwhite (mini-w) transgene in mature mates results in a marked change in their sexual behavior such that they begin to vigorously court other mature males, In transformant populations containing equal numbers of both sexes, most males participate, thus forming male-male courtship chains, circles, and lariats, Mutations that ablate the w transgene function also abolish this inducible behavior. Female sexual behavior does not appear to be altered by ectopic w expression. By contrast, when exposed to an active homosexual courtship environment, non-transformant mates alter their behavior and actively participate in the male-male chaining, These findings demonstrate that, in Drosophila, both genetic and environmental factors play a role in male sexual behavior. RP ZHANG, SD (reprint author), NATL INST NEUROL DISORDERS & STROKE, NEUROCHEM LAB, NEUROGENET UNIT, BETHESDA, MD 20892 USA. RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 45 TC 94 Z9 96 U1 1 U2 12 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 JUN 6 PY 1995 VL 92 IS 12 BP 5525 EP 5529 DI 10.1073/pnas.92.12.5525 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400056 PM 7777542 ER PT J AU WANG, XJ GOLOMB, D RINZEL, J AF WANG, XJ GOLOMB, D RINZEL, J TI EMERGENT SPINDLE OSCILLATIONS AND INTERMITTENT BURST FIRING IN A THALAMIC MODEL - SPECIFIC NEURONAL MECHANISMS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE THALAMUS; NUCLEUS RETICULARIS THALAMI; BIOPHYSICAL NETWORK MODELING; SYNCHRONY ID CELLULAR MECHANISMS; RELAY NEURONS; RHYTHMICITY; NUCLEUS; CAT; RAT AB The rhythmogenesis of 10-Hz sleep spindles is studied in a large-scale thalamic network model with two cell populations: the excitatory thalamocortical (TC) relay neurons and the inhibitory nucleus reticularis thalami (RE) neurons. Spindle-like bursting oscillations emerge naturally from reciprocal interactions between TC and RE neurons. We find that the network oscillations can be synchronized coherently, even though the RE-TC connections are random and sparse, and even though individual neurons fire rebound bursts intermittently in time. When the fast gamma-aminobutyrate type A synaptic inhibition is blocked, synchronous slow oscillations resembling absence seizures are observed. Near-maximal network synchrony is established with even modest convergence in the RE-to-TC projection (as few as 5-10 RE inputs per TC cell suffice), The hyperpolarization-activated cation current (I-h) is found to provide a cellular basis for the intermittency of rebound bursting that is commonly observed in TC neurons during spindles. Such synchronous oscillations with intermittency can be maintained only with a significant degree of convergence for the TC-to-RE projection. C1 NIDDK,MATH RES BRANCH,BETHESDA,MD 20814. RP WANG, XJ (reprint author), UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260, USA. RI Wang, Xiao-Jing/D-2722-2009 NR 31 TC 68 Z9 69 U1 2 U2 7 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 JUN 6 PY 1995 VL 92 IS 12 BP 5577 EP 5581 DI 10.1073/pnas.92.12.5577 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400067 PM 7777551 ER PT J AU TOMURA, H LAZAR, J PHYILLAIER, M NIKODEM, VM AF TOMURA, H LAZAR, J PHYILLAIER, M NIKODEM, VM TI THE N-TERMINAL REGION (A/B) OF RAT-THYROID HORMONE RECEPTORS ALPHA-1, BETA-1, BUT NOT BETA-2 CONTAINS A STRONG THYROID HORMONE-DEPENDENT TRANSACTIVATION FUNCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR TFIIB; RESPONSE ELEMENT; BINDING; ACTIVATION; GENE; IDENTIFICATION; PROTEINS; PROMOTER; INVIVO; CELLS AB In this study we have investigated the role of the N-terminal region of thyroid hormone receptors (TRs) in thyroid hormone (TH)-dependent transactivation of a thymidine kinase promoter containing TH response elements composed either of a direct repeat or an inverted palindrome. Comparison of rat TR beta 1 with TR beta 2 provides an excellent model since they share identical sequences except for their N termini, Our results show that TR beta 2 is an inefficient TH-dependent transcriptional activator. The degree of transactivation corresponds to that observed for the mutant TR Delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2. Thus, TH-dependent activation appears to be associated with two separate domains, The more important region, however, is embedded in the N-terminal domain, Furthermore, the transactivating property of TR alpha 1 was also localized to the N-terminal domain between amino acids 19 and 30. Using a coimmunoprecipitation assay, we show that the differential interaction of the N terminus of TR beta 1 and TR beta 2 with transcription factor LIE correlates with the TR beta 1 activation function, Hence, our results underscore the importance of the N-terminal region of TRs in TH-dependent transactivation and suggest that a transactivating signal is transmitted to the general transcriptional machinery cia a direct interaction of the receptor N-terminal region with transcription factor IIB. C1 NIDDK, GENET & BIOCHEM BRANCH, BETHESDA, MD 20892 USA. NR 32 TC 25 Z9 25 U1 0 U2 1 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 JUN 6 PY 1995 VL 92 IS 12 BP 5600 EP 5604 DI 10.1073/pnas.92.12.5600 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400072 PM 7539921 ER PT J AU YEE, J NASH, TE AF YEE, J NASH, TE TI TRANSIENT TRANSFECTION AND EXPRESSION OF FIREFLY LUCIFERASE IN GIARDIA-LAMBLIA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ELECTROPORATION; GLUTAMATE DEHYDROGENASE; PRIMITIVE EUKARYOTE ID PRIMITIVE EUKARYOTE; GENE; LEISHMANIA; PARASITE; PROTEINS; RNA AB We have developed a gene transfer system for the protozoan parasite Giardia lamblia. This organism is responsible for many cases of diarrhea worldwide and is considered to be one of the most primitive eukaryotes. Expression of a heterologous gene was detected in this parasite after electroporation with appropriate DNA constructs. We constructed a series of transfection plasmids using flanking sequences of the Giardia glutamate dehydrogenase (GDH) gene to drive expression of the firefly luciferase reporter gene. The optimal construct consisted of a GDH/luciferase fusion gene in which the first 18 codons of the GDH gene immediately preceded the luciferase gene; this fusion gene was flanked by the upstream and downstream sequences of the GDH gene. Electroporation of this construct into Giardia yielded luciferase activity that was 3000- to 50,000-fold above background. Removal of either the 5' or 3' GDH flanking sequences from this construct resulted in significantly reduced luciferase activity, and removal of both flanking sequences reduced luciferase activity to background levels. Luciferase activity was proportional to the amount of DNA electroporated and was maximal at 6 hr after electroporation. RP YEE, J (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 27 TC 53 Z9 57 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 JUN 6 PY 1995 VL 92 IS 12 BP 5615 EP 5619 DI 10.1073/pnas.92.12.5615 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400075 PM 7777558 ER PT J AU SENSI, M TRAVERSARI, C RADRIZZANI, M SALVI, S MACCALLI, C MORTARINI, R RIVOLTINI, L FARINA, C NICOLINI, G WOLFEL, T BRICHARD, V BOON, T BORDIGNON, C ANICHINI, A PARMIANI, G AF SENSI, M TRAVERSARI, C RADRIZZANI, M SALVI, S MACCALLI, C MORTARINI, R RIVOLTINI, L FARINA, C NICOLINI, G WOLFEL, T BRICHARD, V BOON, T BORDIGNON, C ANICHINI, A PARMIANI, G TI CYTOTOXIC T-LYMPHOCYTE CLONES FROM DIFFERENT PATIENTS DISPLAY LIMITED T-CELL-RECEPTOR VARIABLE-REGION GENE USAGE IN HLA-A2-RESTRICTED RECOGNITION OF THE MELANOMA ANTIGEN MELAN-A/MART-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; POLYMERASE CHAIN-REACTION; BETA-CHAIN; ALPHA-CHAIN; DIVERSITY; SEQUENCES; CTL; ORGANIZATION; VARIABILITY; EXPRESSION AB To determine whether T-cell-receptor (TCR) usage by T cells recognizing a defined human tumor antigen in the context of the same HLA molecule is conserved, we analyzed the TCR diversity of autologous HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones derived from five patients with metastatic melanoma and specific for the common melanoma antigen Melan-A/MART-1. These clones were first identified among HLA-A2-restricted anti-melanoma CTL clones by their ability to specifically release tumor necrosis factor in response to HLA-A2.1(+) COS-7 cells expressing this tumor antigen, A PCR with variable (V)-region gene subfamily-specific primers was performed on cDNA from each clone followed by DNA sequencing, TCRAV2S1 was the predominant alpha-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. beta-chain V-region usage was also restricted, with either TCRBV14 or TCRBV7 expressed by all but one clone. In addition, a conserved TCRAV2S1/TCRBV14 combination was expressed in four CTL clones from three patients, None of these V-region genes was found in a group of four HLA-A2-restricted CTL clones recognizing different antigens (e.g., tyrosinase) on the autologous tumor, TCR joining regions were heterogeneous, although conserved structural features were observed in the complementarity-determining region 3 sequences, These results indicate that a selective repertoire of TCR genes is used in anti-melanoma responses when the response is narrowed to major histocompatibility complex-restricted antigen-specific interactions. C1 IST NAZL TUMORI,DIV EXPTL ONCOL D,I-20133 MILAN,ITALY. IST SCI HS RAFFAELE,DEPT BIOL & BIOTECHNOL,I-20132 MILAN,ITALY. NCI,BETHESDA,MD 20892. UNIV MAINZ,MED KLIN & POLIKLIN 1,W-6500 MAINZ,GERMANY. LUDWIG INST CANC RES,B-1200 BRUSSELS,BELGIUM. RI Farina, Cinthia/G-8911-2014; Wolfel, Thomas/G-6519-2012; Sensi, Marialuisa/K-5631-2014; Anichini, Andrea/K-1434-2016; Mortarini, Roberta/C-9483-2017; OI Farina, Cinthia/0000-0002-4466-9676; Sensi, Marialuisa/0000-0002-7643-0248; Anichini, Andrea/0000-0001-5096-5538; Mortarini, Roberta/0000-0001-7732-0561; Rivoltini, Licia/0000-0002-2409-6225 NR 37 TC 101 Z9 101 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 6 PY 1995 VL 92 IS 12 BP 5674 EP 5678 DI 10.1073/pnas.92.12.5674 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400087 PM 7777568 ER PT J AU DADA, AJ OLUMIDE, YM HENRARD, DR PHELPS, B PAU, CP QUINN, TC BIGGAR, RJ OBRIEN, TR BLATTNER, WA AF DADA, AJ OLUMIDE, YM HENRARD, DR PHELPS, B PAU, CP QUINN, TC BIGGAR, RJ OBRIEN, TR BLATTNER, WA TI SEARCH FOR HIV-1 GROUP-O INFECTION IN NIGERIA SO LANCET LA English DT Letter C1 LAGOS UNIV TEACHING HOSP,STD DERMATOL CLIN,LAGOS,NIGERIA. ABBOTT LABS,RETROVIRUS MED RES,CHICAGO,IL. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV HIV AIDS,ATLANTA,GA. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD. RP DADA, AJ (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20852, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JUN 3 PY 1995 VL 345 IS 8962 BP 1436 EP 1436 DI 10.1016/S0140-6736(95)92623-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RB441 UT WOS:A1995RB44100037 PM 7760622 ER PT J AU FORMAN, BM GOODE, E CHEN, J ORO, AE BRADLEY, DJ PERLMANN, T NOONAN, DJ BURKA, LT MCMORRIS, T LAMPH, WW EVANS, RM WEINBERGER, C AF FORMAN, BM GOODE, E CHEN, J ORO, AE BRADLEY, DJ PERLMANN, T NOONAN, DJ BURKA, LT MCMORRIS, T LAMPH, WW EVANS, RM WEINBERGER, C TI IDENTIFICATION OF A NUCLEAR RECEPTOR THAT IS ACTIVATED BY FARNESOL METABOLITES SO CELL LA English DT Article ID RETINOID-X-RECEPTOR; THYROID-HORMONE; ECDYSONE RECEPTOR; RXR-BETA; ACID; MEVALONATE; PROTEIN; HETERODIMERIZATION; ULTRASPIRACLE; SUPERFAMILY AB Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that mediate the transcriptional activities of steroids, retinoids, and thyroid hormones. A growing number of related proteins have been identified that possess the structural features of hormone receptors, but that lack known ligands, Known as orphan receptors, these proteins represent targets for novel signaling molecules. We have isolated a mammalian orphan receptor that forms a heterodimeric complex with the retinoid X receptor. A screen of candidate ligands identified farnesol and related metabolites as effective activators of this complex. Farnesol metabolites are generated intracellularly and are required for the synthesis of cholesterol, bile acids, steroids, retinoids, and farnesylated proteins. Intermediary metabolites have been recognized as transcriptional regulators in bacteria and yeast. Our results now suggest that metabolite-controlled intracellular signaling systems are utilized by higher organisms. C1 SALK INST BIOL STUDIES,HOWARD HUGHES MED INST,LA JOLLA,CA 92037. NIEHS,RECEPTOR BIOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,ORGAN CHEM GRP,RES TRIANGLE PK,NC 27709. NIH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40506. UNIV CALIF SAN DIEGO,DEPT CHEM,LA JOLLA,CA 92093. LIGAND PHARMACEUT INC,SAN DIEGO,CA 92121. RP FORMAN, BM (reprint author), SALK INST BIOL STUDIES,GENE EXPRESS LAB,10010 N TORREY PINES RD,LA JOLLA,CA 92037, USA. NR 45 TC 649 Z9 671 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 1995 VL 81 IS 5 BP 687 EP 693 DI 10.1016/0092-8674(95)90530-8 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RB961 UT WOS:A1995RB96100007 PM 7774010 ER PT J AU WERNER, MH RUTH, JR GRONENBORN, AM CLORE, GM AF WERNER, MH RUTH, JR GRONENBORN, AM CLORE, GM TI MOLECULAR-BASIS OF HUMAN 46X,Y SEX REVERSAL REVEALED FROM THE 3-DIMENSIONAL SOLUTION STRUCTURE OF THE HUMAN SRY-DNA COMPLEX SO CELL LA English DT Article ID HMG BOX; BINDING DOMAIN; MINOR-GROOVE; XY FEMALES; NUCLEOPROTEIN STRUCTURES; DETERMINING REGION; DETERMINING LOCUS; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; PROTEINS AB The solution structure of the specific complex between the high mobility group (HMG) domain of SRY (hSRY-HMG), the protein encoded by the human testis-determining gene, and its DNA target site in the promoter of the Mullerian inhibitory substance gene has been determined by multidimensional NMR spectroscopy. hSRY-HMG has a twisted L shape that presents a concave surface (made up of three helices and the N- and C-terminal strands) to the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site occurs exclusively in the minor groove and induces a large conformational change in the DNA. The DNA in the complex has an overall 70 degrees-80 degrees bend and is helically unwound relative to classical A- and B-DNA. The structure of the complex reveals the origin of sequence-specific binding within the HMG-1/HMG-2 family and provides a framework for understanding the effects of point mutations that cause 46X, Y sex reversal at the atomic level. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 49 TC 387 Z9 391 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 1995 VL 81 IS 5 BP 705 EP 714 DI 10.1016/0092-8674(95)90532-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RB961 UT WOS:A1995RB96100009 PM 7774012 ER PT J AU FRANKE, TF YANG, SI CHAN, TO DATTA, K KAZLAUSKAS, A MORRISON, DK KAPLAN, DR TSICHLIS, PN AF FRANKE, TF YANG, SI CHAN, TO DATTA, K KAZLAUSKAS, A MORRISON, DK KAPLAN, DR TSICHLIS, PN TI THE PROTEIN-KINASE ENCODED BY THE AKT PROTOONCOGENE IS A TARGET OF THE PDGF-ACTIVATED PHOSPHATIDYLINOSITOL 3-KINASE SO CELL LA English DT Article ID POLYMERASE CHAIN-REACTION; GROWTH-FACTOR; C-AKT; V-AKT; REGION; EXPRESSION; RECEPTORS; MICE AB The serine/threonine protein kinase encoded by the Akt proto-oncogene is catalytically inactive in serum-starved primary and immortalized fibroblasts. Here we show that Akt and the Akt-related kinase AKT2 are activated by PDGF. The activation was rapid and specific, and it was abrogated by mutations in the Akt Pleckstrin homology (PH) domain. The Akt activation was also shown to depend on PDGFR beta tyrosines Y740 and Y751, which bind phosphatidylinositol 3-kinase (Pl 3-kinase) upon phosphorylation. Moreover, Akt activation was blocked by the Pl 3-kinase-specific inhibitor wortmannin and the dominant inhibitory N17Ras. Conversely, Akt activity was induced following the addition of phosphatidylinositol-3-phosphate to Akt immunoprecipitates from serum-starved cells in vitro, These results identify Akt as a novel target of Pl 3-kinase and suggest that the Akt PH domain may be a mediator of Pl 3-kinase signaling. C1 NCI,FREDERICK CANC RES FACIL & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT SECT,FREDERICK,MD 21702. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. RP FRANKE, TF (reprint author), FOX CHASE CANC CTR,PHILADELPHIA,PA 19111, USA. OI Chan , Tung/0000-0001-6574-9555 FU NCI NIH HHS [R01-CA57436, CA-55063, R01-CA38047] NR 31 TC 1655 Z9 1678 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 1995 VL 81 IS 5 BP 727 EP 736 DI 10.1016/0092-8674(95)90534-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RB961 UT WOS:A1995RB96100011 PM 7774014 ER PT J AU KOUNNAS, MZ LOUKINOVA, EB STEFANSSON, S HARMONY, JAK BREWER, BH STRICKLAND, DK ARGRAVES, WS AF KOUNNAS, MZ LOUKINOVA, EB STEFANSSON, S HARMONY, JAK BREWER, BH STRICKLAND, DK ARGRAVES, WS TI IDENTIFICATION OF GLYCOPROTEIN-330 AS AN ENDOCYTIC RECEPTOR FOR APOLIPOPROTEIN-J/CLUSTERIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE-ATTACK-COMPLEX; ALPHA-2-MACROGLOBULIN RECEPTOR; SULFATED GLYCOPROTEIN-2; HEYMANN NEPHRITIS; DENSITY LIPOPROTEINS; MOLECULAR-CLONING; GENE-EXPRESSION; LDL RECEPTOR; TESTIS FLUID; PROTEIN AB Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density Lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to aporJ with high affinity (K-d = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein Lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell Lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize I-125-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation. C1 AMER RED CROSS,DEPT BIOCHEM,JH HOLLAND LAB,ROCKVILLE,MD 20855. UNIV CINCINNATI,COLL MED,DEPT PHARMACOL & CELL BIOPHYS,CINCINNATI,OH 45267. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL41496]; NIDDK NIH HHS [DK45598]; NIGMS NIH HHS [GM42581] NR 48 TC 181 Z9 183 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 JUN 2 PY 1995 VL 270 IS 22 BP 13070 EP 13075 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB439 UT WOS:A1995RB43900022 PM 7768901 ER PT J AU CHALFANT, CE MISCHAK, H WATSON, JE WINKLER, BC GOODNIGHT, J FARESE, RV COOPER, DR AF CHALFANT, CE MISCHAK, H WATSON, JE WINKLER, BC GOODNIGHT, J FARESE, RV COOPER, DR TI REGULATION OF ALTERNATIVE SPLICING OF PROTEIN-KINASE C-BETA BY INSULIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATED 2-DEOXYGLUCOSE UPTAKE; PHORBOL ESTER TREATMENT; SMOOTH-MUSCLE CELLS; PRE-MESSENGER-RNA; BC3H-1 MYOCYTES; RAT ADIPOCYTES; GLUCOSE-TRANSPORT; PREMESSENGER RNA; DOWN-REGULATION; GROWTH AB Insulin regulates a diverse array of cellular signaling processes involved in the control of growth, differentiation, and cellular metabolism. Insulin increases glucose transport via a protein kinase C (PKC) dependent pathway in BC3H-1 myocytes, but the function of specific PKC isozymes in insulin action has not been elucidated. Two isoforms of PKC beta result via alternative splicing of precursor mRNA. As now shown, both isoforms are present in BC3H-1 myocytes, and insulin induces alternative splicing of the PKC beta mRNA thereby switching expression from PKC beta I to PRC beta II mRNA. This effect occurs rapidly (15 min after insulin treatment) and is dose-dependent. The switch in mRNA is reflected by increases in the protein levels of PKC beta II. High levels of 1a-0-tetradecanoylphorbol-13-acetate, which are commonly used to deplete or down-regulate PKC in cells, also induce the switch to PKC beta II mRNA following overnight treatment, and protein levels of PKC beta II reflected mRNA increases. To investigate the functional importance of the shift in PKC beta isoform expression, stable transfectants of NIH-3T3 fibroblasts overexpressing PKC beta I and PKC beta II were established. The overexpression of PKC beta II but not PKC beta I in NIH-3T3 cells significantly enhanced insulin effects on glucose transport. This suggests that PKC beta II may be more selective than PKC beta I for enhancing the glucose transport effects of insulin in at least certain cells and, furthermore, that insulin can regulate the expression of PKC beta II by alternative mRNA splicing. C1 JAMES A HALEY VET HOSP,RES SERV 151,TAMPA,FL 33612. UNIV S FLORIDA,COLL MED,DEPT BIOCHEM & MOLEC BIOL,TAMPA,FL 33612. UNIV S FLORIDA,COLL MED,DEPT INTERNAL MED,TAMPA,FL 33612. UNIV TAMPA,DEPT CHEM,TAMPA,FL 33606. NCI,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011; Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [DK 38079] NR 41 TC 81 Z9 81 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 JUN 2 PY 1995 VL 270 IS 22 BP 13326 EP 13332 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB439 UT WOS:A1995RB43900058 PM 7768933 ER PT J AU CORCORAN, ML STETLERSTEVENSON, WG AF CORCORAN, ML STETLERSTEVENSON, WG TI TISSUE INHIBITOR OF METALLOPROTEINASE-2 STIMULATES FIBROBLAST PROLIFERATION VIA A CAMP-DEPENDENT MECHANISM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; SWISS 3T3 CELLS; PROTEIN-KINASE; PERTUSSIS TOXIN; DNA-SYNTHESIS; CYCLIC-AMP; TIMP-2; ACCUMULATION; ENHANCEMENT; COLLAGENASE AB In addition to inhibiting the proteolytic activity of the matrix metalloproteinases, tissue inhibitors of metalloproteinases (TIMPs) promote the growth of cells in the absence of other exogenous growth factors. TIMP-2 stimulates the proliferation of fibrosarcoma (HT-1080) cells and normal dermal fibroblasts (Hs68) in a dose-dependent manner. This response is evident as early as 2 h and persists up to 48 h after treatment with recombinant TIMP-2 (rTIMP-2). The specificity of this response is demonstrated by the ability of affinity-purified polyclonal anti-TIMP-2 antibodies to ablate TIMP-2 mitogenesis and by the lack of response to TIMP-1. This response is also blocked by the presence of an adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl) adenine (SQ22536). Although SQ22536 did not affect untreated fibroblasts or fibrosarcoma cells, this inhibitor completely abrogates the proliferative response induced by rTIMP-2. Treatment of these cells with rTIMP-2 also stimulates the production of cAMP in a time-dependent manner that differs for the two cell lines. Moreover, treatment of purified cell membranes with rTIMP-2 suppresses cholera toxin-mediated ADP-ribosylation of the GTP-binding protein, Gs alpha subunit. These results indicate that the alpha beta gamma heterotrimer is dissociated by treatment with rTIMP-2, which may facilitate the Gs alpha-mediated activation of adenylate cyclase and subsequent production of cAMP. Since cAMP binds to the regulatory subunit of cAMP-dependent protein kinase and activates kinase activity, we evaluated how treatment with rTIMP-2 affected both these parameters. We demonstrate in this report that the cAMP produced in response to treatment with rTIMP-2 binds to the type I regulatory subunit of cAMP-dependent protein kinase and stimulates kinase activity. These results are the first demonstration that TIMP-2 directly activates adenylate cyclase to produce cAMP, which increases cAMP-dependent protein kinase activity, resulting in stimulation of fibroblast mitogenesis. C1 NCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 47 TC 152 Z9 155 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 JUN 2 PY 1995 VL 270 IS 22 BP 13453 EP 13459 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB439 UT WOS:A1995RB43900074 PM 7768948 ER PT J AU MA, Y ITO, Y FOUCAULT, A AF MA, Y ITO, Y FOUCAULT, A TI RESOLUTION OF GRAM QUANTITIES OF RACEMATES BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID CENTRIFUGAL PARTITION CHROMATOGRAPHY; ENANTIOMERS; SEPARATION AB Gram quantities of (+/-)-dinitrobenzoyl amino acids were separated by high-speed counter-current chromatography (CCC) using N-dodecanoyl-L-proline-3,5-dimethylanilide as a chiral selector (CS). Standard and pH-zone-refining CCC techniques were compared. By using the standard technique, 10 mg to a maximum of 1 g of samples was resolved in 2-9 h simply by increasing the concentration of the CS in the stationary phase. By using pH-zone-refining CCC, even more sample (2 g) was efficiently separated in less time (3 h). In both techniques, leakage of CS from the column was negligible. The method requires no solid support and the same column can be used repeatedly to separate a variety of enantiomers by dissolving appropriate chiral selectors in the stationary phase. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. CNRS,BIOORGAN & BIOTECHNOL LAB,ESR 71,F-75005 PARIS,FRANCE. NR 30 TC 49 Z9 51 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 2 PY 1995 VL 704 IS 1 BP 75 EP 81 DI 10.1016/0021-9673(95)00148-G PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RD314 UT WOS:A1995RD31400007 PM 7599747 ER PT J AU RESNICK, SM TOROK, DS GIBSON, DT AF RESNICK, SM TOROK, DS GIBSON, DT TI CHEMOENZYMATIC SYNTHESIS OF CHIRAL BORONATES FOR THE H-1-NMR DETERMINATION OF THE ABSOLUTE-CONFIGURATION AND ENANTIOMERIC EXCESS OF BACTERIAL AND SYNTHETIC CIS-DIOLS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note ID OXIDATION; STEREOCHEMISTRY; DIHYDRODIOLS; NAPHTHALENE; METABOLITES; TOLUENE; ARENES C1 UNIV IOWA,CTR BIOCATALYSIS & BIOPROC,IOWA CITY,IA 52240. NIMH,BETHESDA,MD 20892. RP RESNICK, SM (reprint author), UNIV IOWA,DEPT MICROBIOL,IOWA CITY,IA 52240, USA. NR 24 TC 59 Z9 59 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 2 PY 1995 VL 60 IS 11 BP 3546 EP 3549 DI 10.1021/jo00116a050 PG 4 WC Chemistry, Organic SC Chemistry GA RB479 UT WOS:A1995RB47900050 ER PT J AU HOLLINGSHEAD, MG ALLEY, MC CAMALIER, RF ABBOTT, BJ MAYO, JG MALSPEIS, L GREVER, MR AF HOLLINGSHEAD, MG ALLEY, MC CAMALIER, RF ABBOTT, BJ MAYO, JG MALSPEIS, L GREVER, MR TI IN-VIVO CULTIVATION OF TUMOR-CELLS IN HOLLOW FIBERS SO LIFE SCIENCES LA English DT Article DE TUMOR CELLS; HOLLOW FIBER; IN VIVO CELL CULTIVATION ID LINES; MICE; DRUGS; FEASIBILITY; XENOGRAFTS; GROWTH; MODELS; INVIVO; ISLETS; ASSAY AB Advancement of potential anti-cancer agents from ''discovery'' in an in vitro screen to pre-clinical development requires a demonstration of in vivo efficacy in one or more animal models of neoplastic disease. Most such models require considerable materials in terms of laboratory animals and test compound as well as substantial amounts of time (and cost) to determine whether a given experimental agent or series of agents have even minimal anti-tumor activity. The present study was initiated to assess the feasibility of employing an alternate methodology for preliminary in vivo evaluations of therapeutic efficacy. Results of experimentation to date demonstrate that a hollow fiber encapsulation/implantation methodology provides quantitative indices of drug efficacy with minimum expenditures of time and materials. Following further pharmacologic calibrations, the hollow fiber technique is anticipated (a) to identify compounds having moderate to prominent anti-cancer activity and (b) to facilitate the identification of sensitive tumor cell line ''targets'' and optimal or near-optimal treatment regimens for subsequent testing using standard in vivo solid tumor models. The potential suitability of this methodology is demonstrated with several standard anti-neoplastic agents. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL TESTING BRANCH,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,FREDERICK,MD 21702. NR 17 TC 237 Z9 249 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 2 PY 1995 VL 57 IS 2 BP 131 EP 141 DI 10.1016/0024-3205(95)00254-4 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RC184 UT WOS:A1995RC18400006 PM 7603295 ER PT J AU BOHEN, SP KRALLI, A YAMAMOTO, KR AF BOHEN, SP KRALLI, A YAMAMOTO, KR TI HOLDEM AND FOLDEM - CHAPERONES AND SIGNAL-TRANSDUCTION SO SCIENCE LA English DT Editorial Material ID HEAT-SHOCK PROTEIN; RECEPTOR; BINDING C1 UNIV CALIF SAN FRANCISCO,DEPT MOLEC & CELLULAR PHARMACOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. RP BOHEN, SP (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 16 TC 164 Z9 167 U1 1 U2 4 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 2 PY 1995 VL 268 IS 5215 BP 1303 EP 1304 DI 10.1126/science.7761850 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB198 UT WOS:A1995RB19800026 PM 7761850 ER PT J AU WEHR, TA AF WEHR, TA TI RESPONSE OF HUMAN MELATONIN SECRETION TO CHANGES IN NIGHTLENGTH (SCOTOPERIOD) - IMPLICATIONS FOR SEASONAL-AFFECTIVE-DISORDER AND OTHER PSYCHIATRIC ILLNESSES SO ACTA NEUROPSYCHIATRICA LA English DT Article DE MELATONIN; CIRCADIAN RHYTHM; SEASONAL AFFECTIVE DISORDER; SEASONS; DEPRESSION; GENDER ID PHOTOPERIOD C1 NIMH,CLIN PSYCHOBIOL BRANCH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 9 TC 0 Z9 0 U1 0 U2 0 PU REED HEALTHCARE COMMUNICATIONS PI AMSTERDAM PA P O BOX 1126, 1000 AMSTERDAM, NETHERLANDS SN 0924-2708 J9 ACTA NEUROPSYCHIATR JI Acta Neuropsychiatr. PD JUN PY 1995 VL 7 IS 2 BP 35 EP 37 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RE180 UT WOS:A1995RE18000009 PM 26965346 ER PT J AU REDDY, TR SUHASINI, M RAPPAPORT, J LOONEY, DJ KRAUS, G WONGSTAAL, F AF REDDY, TR SUHASINI, M RAPPAPORT, J LOONEY, DJ KRAUS, G WONGSTAAL, F TI MOLECULAR-CLONING AND CHARACTERIZATION OF A TAR-BINDING NUCLEAR FACTOR FROM T-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANS-ACTIVATOR GENE; LONG TERMINAL REPEAT; III HTLV-III; HIV-1 TAT; RESPONSIVE SEQUENCE; LOOP SEQUENCE; NASCENT RNA; PROTEIN; TYPE-1 AB The Tat protein of the human immunodeficiency virus type 1 (HIV-1) activates the expression of viral mRNA through a cis-acting element in the LTR termed TAR, TAR RNA forms a stable stem-loop structure, Mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and three unpaired bases in the stem (bulge) are important for Tat activation, Using the in vitro-transcribed TAR RNA as a probe, we have cloned a gene (TARBP-b) that encodes a TAR-binding protein from a cDNA expression library derived from Hut-78 cells, Expression of the 1.4-kb TARBP-b mRNA was observed in all mammalian cell lines tested, TARBP-b binds specifically to the bulge region of TAR RNA and trans-activates the HIV-1 long terminal repeat in the presence of ptat and prev expression plasmids. These results suggest that TARBP-b contributes to tat-mediated trans-activation. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. GEORGE WASHINGTON UNIV,NIDR,DEPT MED,DIV RENAL DIS & HYPERTENS,ORAL MED LAB,BETHESDA,MD 20892. SAN DIEGO VET ADM HOSP,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. FU NIAID NIH HHS [AI 31378] NR 39 TC 17 Z9 18 U1 0 U2 1 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 JUN PY 1995 VL 11 IS 6 BP 663 EP 669 DI 10.1089/aid.1995.11.663 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RE377 UT WOS:A1995RE37700001 PM 7576925 ER PT J AU MARGOLIS, LB GLUSHAKOVA, S BAIBAKOV, B ZIMMERBERG, J AF MARGOLIS, LB GLUSHAKOVA, S BAIBAKOV, B ZIMMERBERG, J TI SYNCYTIUM FORMATION IN CULTURED HUMAN LYMPHOID-TISSUE - FUSION OF IMPLANTED HIV GLYCOPROTEIN 120/41-EXPRESSING CELLS WITH NATIVE CD4(+) CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; HTLV-III/LAV ENVELOPE; INSITU HYBRIDIZATION; GENERALIZED LYMPHADENOPATHY; HOMOSEXUAL MEN; SYNDROME AIDS; EXPRESSION; INFECTION; MECHANISM AB While glycoprotein gp120/41 clearly causes HIV-infected cells to form syncytia in monolayers and in suspension, there is unfortunately scant knowledge on syncytium formation in tissues, We implanted gp120/41-expressing cells labeled with fluorescent particles inside blocks of human lymphoid tissue kept in long-term histoculture. Observed by confocal microscopy, together with immunohistochemical and morphological analysis of implanted cells, more than one-third of these gp120/41-expressing cells fused with native CD4(+) cells of the host tissue, yielding small (three to five nuclei) syncytia, Such widespread fusion of gp120/41-expressing cells in tissue in vitro, together with the finding of increased virulence of syncytium-inducing isolates of HIV, support the hypothesis that syncytium formation within lymph tissue of HIV-infected individuals contributes to AIDS pathogenesis.(1-4) This system and the methods developed may provide a way to study HIV-infected cells inside the very tissue whose destruction may prevent immune system repopulation. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 58 TC 8 Z9 8 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 JUN PY 1995 VL 11 IS 6 BP 697 EP 704 DI 10.1089/aid.1995.11.697 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RE377 UT WOS:A1995RE37700005 PM 7576929 ER PT J AU VITKOVIC, L STOVER, E KOSLOW, SH AF VITKOVIC, L STOVER, E KOSLOW, SH TI ANIMAL-MODELS RECAPITULATE ASPECTS OF HIV CNS DISEASE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; VIRUS-INFECTION; NERVOUS-SYSTEM; MURINE AIDS; SCID MICE; NEUROPATHOLOGY; ENCEPHALOPATHY; BRAIN; SERUM; MOUSE AB Neurobehavioral and pathological data indicate that the central nervous system (CNS) becomes infected with HIV-1 soon after the virus enters the body, However, neuropathogenesis of HIV-1 infection is difficult to investigate because the brain parenchyma is riot accessible to sampling during the course of AIDS, The second compartment of the CNS, cerebrospinal fluid (CSF), is accessible to sampling but how changes in the CSF relate to the changes in the parenchyma is poorly understood, Thus, knowledge of the neuropathogenesis of HIV-1 infection predominantly stems from either postmortem or in vitro studies, This raises the need for animal models of HIV infection of the CNS, Such models have been developed and are briefly reviewed here, The models faithfully recapitulate some aspects of the HIV/CNS disease, Appropriate neuropathological changes and neurobehavioral dysfunction (e.g., cognitive and motor deficits) occur in SIV-infected macaques, Central sensory electrophysiological changes and sleep disturbances occur in FIV-infected cats, Infection of the brain and behavioral changes comparable to some of the changes seen in humans occur in mice infected with a mixture of murine leukemia viruses, Genetically immunodeficient mice (e.g., SCID) accept HIV-infected human organs and or cell grafts, Evidence summarized here indicates that these HuSCID animals undergo neuropathological changes similar to those observed in brains of individuals who died with AIDS, Thus, presently available animal models provide an opportunity to investigate HIV/CNS disease, and to develop and test therapeutic interventions to prevent or cure the disease. C1 NIMH,OFF AIDS,ROCKVILLE,MD 20857. RP VITKOVIC, L (reprint author), NIMH,DIV NEUROSCI & BEHAV SCI,5600 FISHERS LANE,ROOM 11C-06,ROCKVILLE,MD 20857, USA. NR 49 TC 18 Z9 18 U1 1 U2 1 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 JUN PY 1995 VL 11 IS 6 BP 753 EP 759 DI 10.1089/aid.1995.11.753 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RE377 UT WOS:A1995RE37700012 PM 7576936 ER PT J AU CRUM, RM MUNTANER, C EATON, WW ANTHONY, JC AF CRUM, RM MUNTANER, C EATON, WW ANTHONY, JC TI OCCUPATIONAL STRESS AND THE RISK OF ALCOHOL-ABUSE AND DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL; ABUSE; DEPENDENCE; EPIDEMIOLOGY; OCCUPATION ID DIAGNOSTIC INTERVIEW SCHEDULE; CORONARY HEART-DISEASE; UNITED-STATES; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; SEX-DIFFERENCES; WORK ORGANIZATION; PROBLEM DRINKING; GENDER-ROLES AB Using prospective data, we examined the relationship between occupational stress and risk for alcohol disorders. Consistent with the Demand/Control model for psychosocial work environments, we hypothesized that individuals working in high-strain occupations (jobs with high demands and low control) would be at increased risk for alcohol abuse-dependence relative to those in low-strain occupations (jobs with low demands and high control). We classified high occupational strain into two categories: (1) jobs with high psychological demands and low control, and (2) those with high physical demands and low control. A total of 18,571 study subjects were selected in 1980-1984 by taking probability samples of adult household residents at five sites of the Epidemiologic Catchment Area Program. At baseline, participants completed standardized interviews that measured sociodemographic variables and assessed whether they had met diagnostic criteria for currently or formerly active alcohol abuse-dependence syndromes. The interviews were readministered 1 year later to identify cases among the participants. Subjects were sorted into risk sets by age and residence census tract, and persons with a previous history of alcohol abuse or dependence, as well as those who were over 64 years or had no history of full-time employment, were excluded. Among the 507 participants included in the risk sets, there were 126 incident cases of alcohol abuse-dependence and 381 age and residence-matched noncases. Relative to low-strain employment, men were found to be 27.5 times more likely to develop alcohol abuse-dependence if they had been employed in a high-strain job classified as having high psychological demands and low control (p = 0.008), and 3.4 times at higher risk for an alcohol disorder if they were employed in high-strain jobs with high physical demands and low control (p = 0.03). No appreciable risk was found for women in any of the high-strain job categories. The results highlight occupational stress as a potential risk factor for alcohol abuse and dependence, and add to the growing body of literature on relationships between psychosocial work environment and disease states. If confirmed in other studies, these findings identify potential sources of preventive strategies for alcohol disorders. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NIMH,SOCIOENVIRONM STUDIES LAB,BETHESDA,MD. RI Muntaner, C/A-5043-2010 FU NIAAA NIH HHS [K20 AA000168, AA00168]; NIDA NIH HHS [DA03992, DA04823] NR 88 TC 77 Z9 79 U1 15 U2 31 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1995 VL 19 IS 3 BP 647 EP 655 DI 10.1111/j.1530-0277.1995.tb01562.x PG 9 WC Substance Abuse SC Substance Abuse GA RE228 UT WOS:A1995RE22800019 PM 7573788 ER PT J AU TAMURA, K FUKUDA, Y ISHIZAKI, M MASUDA, Y YAMANAKA, N FERRANS, VJ AF TAMURA, K FUKUDA, Y ISHIZAKI, M MASUDA, Y YAMANAKA, N FERRANS, VJ TI ABNORMALITIES IN ELASTIC FIBERS AND OTHER CONNECTIVE-TISSUE COMPONENTS OF FLOPPY MITRAL-VALVE SO AMERICAN HEART JOURNAL LA English DT Article ID HUMAN-HEART VALVES; CHORDAE TENDINEAE; NUCHAL LIGAMENT; POSTNATAL SHEEP; COLLAGEN GENES; PROLAPSE; PROTEOGLYCANS; RUPTURE; AORTA; FETAL AB Histologic, immunohistochemical, and ultrastructural studies were performed on 12 floppy mitral valves, 4 mitral valves showing focal myxomatous changes without prolapse, and 3 normal mitral valves. All floppy mitral valves were thickened by deposits of proteoglycans and also showed diverse structural abnormalities in collagen and elastic fibers. From these observations we conclude that (1) the structure of all major components of connective tissue in floppy mitral valves is abnormal; (2) alterations in collagen and accumulations of proteoglycans are nonspecific changes that may be caused by the abnormal mechanical forces to which floppy mitral valves are subjected because of their excessively large surface area; (3) the presence of excessive amounts of proteoglycans may interfere with the normal assembly of collagen and elastic fibers; (4) abnormalities of elastic fibers resemble those in other conditions characterized by structural dilatation or tissue expansion; and (5) alterations in elastin could result from defective formation, increased degradation, or both. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP TAMURA, K (reprint author), NIPPON MED COLL,DEPT PATHOL,BUNKYO KU,1-1-5 SENDAGI,TOKYO 113,JAPAN. NR 30 TC 92 Z9 96 U1 1 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1995 VL 129 IS 6 BP 1149 EP 1158 DI 10.1016/0002-8703(95)90397-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RA821 UT WOS:A1995RA82100015 PM 7754947 ER PT J AU PAWLOSKY, RJ SALEM, N AF PAWLOSKY, RJ SALEM, N TI ETHANOL EXPOSURE CAUSES A DECREASE IN DOCOSAHEXAENOIC ACID AND AN INCREASE IN DOCOSAPENTAENOIC ACID IN FELINE BRAINS AND RETINAS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ALCOHOL; DOCOSAHEXAENOIC ACID; ARACHIDONIC ACID; LINOLEIC ACID; LINOLENIC ACID; BRAIN; RETINA; FELINE; LIVER; DESATURATION ID PHOSPHOLIPID-COMPOSITION; FATTY-ACIDS; RAT-LIVER; TISSUE; LIPIDS AB Alcohol altered the fatty acyl composition of the liver, brain, and retina of domestic felines that were maintained on a diet having low, but adequate, amounts of essential fatty acids. For 8 mo, seven adult cats were provided a diet with 10% fat (by wt), consisting of a 9:1 ratio of hydrogenated coconut oil:corn oil. During 6 of these 8 mo, four of the cats were given oral daily doses of a 95% ethanol solution (1.2 g . kg(-1). d(-1)). Cats were killed and the fatty acyl composition of tissues were determined. In the plasma and livers of the alcohol-exposed animals, there were significant decreases in the concentrations of 18:2 omega 6, 20:4 omega 6, 22:5 omega 3, and 22:6 omega 3 and increases in the concentrations of the nonessential fatty acids 16:1 omega 7, 18:1 omega 9, and 20:3 omega 9. In the brains and retinas of the alcohol-exposed animals, 22:6 omega 3 decreased by 17% and there was a compensatory increase in 22:5 omega 6. In the retinas, the concentration of 22:5 omega 6 increased by 250%. The reciprocal change in the ratio of 22:6 omega 3 to 22:5 omega 6 is known to be associated with a loss in nervous system function and may provide a biochemical mechanism underlying some of the neuropathology associated with alcoholism. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,MEMBRANE BIOCHEM & BIOPHYS LAB,ROCKVILLE,MD 20852. NR 33 TC 63 Z9 64 U1 1 U2 2 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1995 VL 61 IS 6 BP 1284 EP 1289 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RB110 UT WOS:A1995RB11000018 PM 7762532 ER PT J AU HEIMENDINGER, J VANDUYN, MAS AF HEIMENDINGER, J VANDUYN, MAS TI DIETARY BEHAVIOR-CHANGE - THE CHALLENGE OF RECASTING THE ROLE OF FRUIT AND VEGETABLES IN THE AMERICAN DIET SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE COMMUNITY NUTRITION; PROGRAM DEVELOPMENT; BEHAVIOR CHANGE THEORIES; FRUIT AND VEGETABLE CONSUMPTION ID CANCER PREVENTION; STRATEGIES; NUTRITION; REDUCTION AB We present an overview of national trends in fruit and vegetable intake and background information on the development of the 5 a Day for Better Health program; which is a national social marketing program created in 1991 to promote consumption by Americans of five or more servings of fruit and vegetables daily. Using the 5 a Day program as an example, we highlight the importance of moving beyond consumption data when approaching a population with a message about healthy eating. In doing so, we incorporate the assessment of marketing data and employ behavioral change theories that are important in modifying behavior. Finally, drawing from the dietary themes of the Mediterranean diet, we propose a new strategy that builds on the good taste and attractiveness of fruit and vegetables, in combination with a health message as a way for health promotion professionals to enhance the role of fruit and vegetables in American cuisine and to help move Americans toward increased fruit and vegetable consumption. C1 ROW SCI INC, ROCKVILLE, MD 20850 USA. RP HEIMENDINGER, J (reprint author), NCI, DIV CANC PREVENT & CONTROL, 9000 ROCKVILLE PIKE, EPN 330, BETHESDA, MD 20892 USA. NR 33 TC 44 Z9 44 U1 1 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1995 VL 61 IS 6 SU S BP 1397S EP 1401S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RC565 UT WOS:A1995RC56500015 ER PT J AU HAMMOND, EH HENSON, DE AF HAMMOND, EH HENSON, DE TI THE ROLE OF PATHOLOGISTS IN CANCER-PATIENT STAGING SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID TNM CLASSIFICATION; PROGNOSTIC FACTORS C1 UNIV UTAH,SCH MED,SALT LAKE CITY,UT. NCI,BETHESDA,MD 20892. COLL AMER PATHOLOGISTS,NORTHFIELD,IL 60093. RP HAMMOND, EH (reprint author), UNIV UTAH,LATTER DAY ST HOSP,DEPT PATHOL,SALT LAKE CITY,UT, USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1995 VL 103 IS 6 BP 679 EP 680 PG 2 WC Pathology SC Pathology GA RC241 UT WOS:A1995RC24100003 PM 7785649 ER PT J AU BRINTON, LA MALONE, KE COATES, RJ SCHOENBERG, JB SWANSON, CA DALING, JR STANFORD, JL AF BRINTON, LA MALONE, KE COATES, RJ SCHOENBERG, JB SWANSON, CA DALING, JR STANFORD, JL TI BREAST IMPLANTS AND SUBSEQUENT BREAST-CANCER RISK SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NATL CANC INST,BETHESDA,MD. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S85 EP S85 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800334 ER PT J AU BROWN, C SUBAR, AF ZIEGLER, RG HARTMAN, A THOMPSON, F SCHATZKIN, A AF BROWN, C SUBAR, AF ZIEGLER, RG HARTMAN, A THOMPSON, F SCHATZKIN, A TI METHOD FOR THE DEVELOPMENT OF A NUTRIENT AND PORTION SIZE DATABASE FOR A NEW FOOD FREQUENCY QUESTIONNAIRE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S12 EP S12 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800044 ER PT J AU BRUNELLE, J BHAT, M AF BRUNELLE, J BHAT, M TI DOES ORTHODONTICS MAKE A DIFFERENCE - OCCLUSION DATA FROM NHANES-III, PHASE-I SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S9 EP S9 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800035 ER PT J AU DORGAN, JF GREENHUT, S DAMATO, J BROWN, C AF DORGAN, JF GREENHUT, S DAMATO, J BROWN, C TI RELIABILITY AND VALIDITY OF SERUM HORMONE MMEASUREMENTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20895. OGDEN BIOSERV CORP,GAITHERSBURG,MD 20879. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S45 EP S45 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800178 ER PT J AU HANSON, RL DECOURTEN, M NARAYAN, KMV FERNANDES, R ROUMAIN, JML PETTITT, DJ BENNETT, PH KNOWLER, WC AF HANSON, RL DECOURTEN, M NARAYAN, KMV FERNANDES, R ROUMAIN, JML PETTITT, DJ BENNETT, PH KNOWLER, WC TI INCREASING INCIDENCE OF DIABETES IN SUCCESSIVE BIRTH COHORTS OF PIMA-INDIANS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK,DAES,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S62 EP S62 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800245 ER PT J AU HERMAN, AA HOFFMAN, HJ GOLDENBERG, RL BAKKETEIG, L YU, KF CLIVER, SP AF HERMAN, AA HOFFMAN, HJ GOLDENBERG, RL BAKKETEIG, L YU, KF CLIVER, SP TI INTRAUTERINE GROWTH-RETARDATION, PRETERM BIRTH AND LONG-TERM NEURODEVELOPMENTAL OUTCOME - RESULTS FROM 2 POPULATION-BASED COHORT STUDIES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S23 EP S23 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800090 ER PT J AU KAMEL, F BAIRD, DD UMBACH, DM GREEN, AM AF KAMEL, F BAIRD, DD UMBACH, DM GREEN, AM TI METABOLIC, DIETARY, AND REPRODUCTIVE DETERMINANTS OF SEX-HORMONE BINDING GLOBULIN (SHBG) LEVELS IN POSTMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S4 EP S4 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800015 ER PT J AU KLEBANOFF, MA SHIONO, PH CAREY, JC AF KLEBANOFF, MA SHIONO, PH CAREY, JC TI PHYSICAL-ACTIVITY DURING PREGNANCY AND PRETERM DELIVERY REPRISED SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S74 EP S74 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800290 ER PT J AU PINKERTON, L BIAGINI, R WARD, E HULL, R BOENIGER, M SCHNORR, T LUSTER, M AF PINKERTON, L BIAGINI, R WARD, E HULL, R BOENIGER, M SCHNORR, T LUSTER, M TI A STUDY OF THE IMMUNOTOXIC EFFECTS OF LEAD SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC 27799. NIOSH,CINCINNATI,OH 45226. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S7 EP S7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800027 ER PT J AU POTOSKY, AL MILLER, BA ALBERTSEN, PC KRAMER, BS AF POTOSKY, AL MILLER, BA ALBERTSEN, PC KRAMER, BS TI THE ROLE OF INCREASING DETECTION IN THE RISING INCIDENCE OF PROSTATE-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S27 EP S27 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800105 ER PT J AU ROWLAND, A BAIRD, D SHORE, D DARDEN, B WILCOX, A AF ROWLAND, A BAIRD, D SHORE, D DARDEN, B WILCOX, A TI ETHYLENE-OXIDE MAY BE ASSOCIATED WITH SPONTANEOUS-ABORTION AND PREMATURITY IN FEMALE DENTAL ASSISTANTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S51 EP S51 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800200 ER PT J AU SANDLER, DP SHORE, DL LIU, E BLOOMFIELD, CD AF SANDLER, DP SHORE, DL LIU, E BLOOMFIELD, CD TI EXPOSURE TO CHEMICALS AND RISK FOR MYELODYSPLASTIC SYNDROME (MDS) SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S60 EP S60 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800235 ER PT J AU SWANSON, CA COATES, RJ SCHOENBERG, JB MALONE, KE GAMMON, MD STANFORD, JL SHORR, LJ POTISCHMAN, NA BRINTON, LA AF SWANSON, CA COATES, RJ SCHOENBERG, JB MALONE, KE GAMMON, MD STANFORD, JL SHORR, LJ POTISCHMAN, NA BRINTON, LA TI BODY-SIZE AND BREAST-CANCER RISK AMONG WOMEN UNDER AGE 45 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. EMORY UNIV,DEPT EPIDEMIOL,ATLANTA,GA 30322. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S14 EP S14 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800054 ER PT J AU TROISI, R SCHAIRER, C CHOW, WH BRINTON, L AF TROISI, R SCHAIRER, C CHOW, WH BRINTON, L TI A PROSPECTIVE-STUDY OF REPRODUCTIVE FACTORS, EXOGENOUS HORMONE USE AND RISK OF COLORECTAL-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S70 EP S70 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800277 ER PT J AU WARD, MH MARK, SD CANTOR, KP WEISENBURGER, D CORREA, A ZAHM, SH AF WARD, MH MARK, SD CANTOR, KP WEISENBURGER, D CORREA, A ZAHM, SH TI RISK OF NON-HODGKINS-LYMPHOMA AND DRINKING-WATER NITRATE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S32 EP S32 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800127 ER PT J AU WILCOX, AJ BAIRD, DD WEINBERG, CR HORNSBY, PP HERBST, AL AF WILCOX, AJ BAIRD, DD WEINBERG, CR HORNSBY, PP HERBST, AL TI FERTILITY OF MEN WHO WERE PRENATALLY EXPOSED TO DES IN A RANDOMIZED CLINICAL-TRIAL SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV CHICAGO,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S81 EP S81 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800317 ER PT J AU PEARSON, JL REYNOLDS, CF KUPFER, DJ LEBOWITZ, BD AF PEARSON, JL REYNOLDS, CF KUPFER, DJ LEBOWITZ, BD TI OUTCOME MEASURES IN LATE-LIFE DEPRESSION SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID SCALE; SUICIDE; IMPACT; STRESS AB The constructs and suggested measures listed here are recommended for inclusion in clinical treatment trials of late-life depression to optimize the return on the significant effort involved in these studies. The suggested measures have shown utility in studies documenting outcomes in depression studies; however the measures listed are by no means to be interpreted as exhaustive. The authors propose that consistent use of a broad set of outcome measures will assist clinicians and policymakers in the identification of appropriate treatments for older, depressed patients. RP PEARSON, JL (reprint author), NIMH,RM 18-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 45 TC 6 Z9 6 U1 7 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SUM PY 1995 VL 3 IS 3 BP 191 EP 197 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA RG768 UT WOS:A1995RG76800002 ER PT J AU PRAS, E RABEN, N GOLOMB, E ARBER, N AKSENTIJEVICH, I SCHAPIRO, JM HAREL, D KATZ, G LIBERMAN, U PRAS, M KASTNER, DL AF PRAS, E RABEN, N GOLOMB, E ARBER, N AKSENTIJEVICH, I SCHAPIRO, JM HAREL, D KATZ, G LIBERMAN, U PRAS, M KASTNER, DL TI MUTATIONS IN THE SLC3A1 TRANSPORTER GENE IN CYSTINURIA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMINO-ACID-TRANSPORT; EXPRESSION CLONING; KIDNEY CDNA; SEQUENCE; OOCYTES; SYSTEM AB Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid-transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in ah of eight Ashkenazi Jewish carrier chromosomes examined, This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. BEILINSON MED CTR,DEPT MED D,IL-49100 PETAH TIQWA,ISRAEL. BEILINSON MED CTR,DEPT METAB,IL-49100 PETAH TIQWA,ISRAEL. BEILINSON MED CTR,DEPT CLIN LABS,IL-49100 PETAH TIQWA,ISRAEL. HADASSAH MED CTR,DEPT UROL,IL-91120 JERUSALEM,ISRAEL. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT PATHOL,IL-69978 TEL AVIV,ISRAEL. NR 24 TC 66 Z9 67 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1995 VL 56 IS 6 BP 1297 EP 1303 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RA794 UT WOS:A1995RA79400006 PM 7539209 ER PT J AU CULLEN, M ERLICH, H KLITZ, W CARRINGTON, M AF CULLEN, M ERLICH, H KLITZ, W CARRINGTON, M TI MOLECULAR MAPPING OF A RECOMBINATION HOTSPOT LOCATED IN THE 2ND INTRON OF THE HUMAN TAP2 LOCUS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II REGION; E-BETA GENE; MEIOTIC RECOMBINATION; LINKAGE DISEQUILIBRIUM; CROSSING-OVER; HUMAN INSULIN; HOT SPOT; MOUSE; DNA AB Recombination across the HLA class II region is not randomly distributed, as indicated by both strong linkage disequilibrium within the 100 kb encompassing the DRB1-DQA1-DQB1 loci and complete equilibrium between TAP1 and TAP2, the closest variant sites of which are <15 kb. In an attempt to explain these observations, 39 novel polymorphic markers in a region encompassing the TAP, LMP, and DOB genes were used to delineate the site of crossover in 11 class II recombinant chromosomes. SSCP demonstrated that two recombination events occurred within an 850-bp interval in the second intron of TAP2, which separates the variant sites of TAP1 and TAP2. These data indicate the presence of a recombination hotspot, the first to be identified from the analysis of familial transmission in the human major histocompatibility complex. The region of crossover was cloned and sequenced from one of the recombinants, further defining the crossover site to a 138-bp segment nested within the 850-bp region. This represents the most precisely defined region of recombination in the human genome. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. ROCHE MOLEC SYST,DEPT HUMAN GENET,ALAMEDA,CA. UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,BERKELEY,CA. FU NIGMS NIH HHS [GM35326] NR 44 TC 74 Z9 77 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1995 VL 56 IS 6 BP 1350 EP 1358 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA RA794 UT WOS:A1995RA79400013 PM 7762558 ER PT J AU FIGGS, LW DOSEMECI, M BLAIR, A AF FIGGS, LW DOSEMECI, M BLAIR, A TI UNITED-STATES NON-HODGKINS-LYMPHOMA SURVEILLANCE BY OCCUPATION 1984-1989 - A 24-STATE DEATH CERTIFICATE STUDY SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE OCCUPATIONAL EXPOSURE; NON-HODGKINS LYMPHOMA; DEATH CERTIFICATES; MORTALITY ODDS RATIO; AFRICAN-AMERICANS; BLACKS ID PROPORTIONATE MORTALITY RATIO; MALIGNANT-LYMPHOMAS; MULTIPLE-MYELOMA; PHENOXY HERBICIDES; CANCER MORTALITY; RISK; EXPOSURE; WORKERS; LEUKEMIA; HAZARDS AB Death certificates from 23,890 male and female non-Hodgkin's lymphoma (NHL) cases and 119,450 noncancer controls from 24 states for the period 1984-1989 were used to generate hypotheses regarding occupational associations. Cases were frequency matched by age, race, and gender with five controls per case. Odds ratios were calculated for 231 industries and 509 occupations. Significant associations were observed for a variety of white-collar professionals (i.e., real estate agents, secretaries, bookkeepers, teachers, postal employees, business agents, engineers, chemists, and medical professionals) and blue-collar occupations (i.e., firefighters, farm managers, aircraft mechanics, electronic repairers, mining machine operators, and crane and tower operators). (C) 1995 Wiley-Liss, Inc.* RP FIGGS, LW (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,RM 418,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 81 TC 32 Z9 32 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1995 VL 27 IS 6 BP 817 EP 835 DI 10.1002/ajim.4700270606 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QZ946 UT WOS:A1995QZ94600005 PM 7645576 ER PT J AU OCONNELL, BC TENHAGEN, KG LAZOWSKI, KW TABAK, LA BAUM, BJ AF OCONNELL, BC TENHAGEN, KG LAZOWSKI, KW TABAK, LA BAUM, BJ TI FACILITATED DNA TRANSFER TO RAT SUBMANDIBULAR-GLAND IN-VIVO AND GRP-CA GENE-REGULATION SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Note DE GENE EXPRESSION; SALIVARY GLAND; GENE THERAPY; EXOCRINE GLAND ID ACID-RICH PROTEINS; ADENOVIRUS TYPE-5; TRANSGENIC MICE; EXPRESSION; DELIVERY; INVIVO; PROMOTER; MUSCLE; CELLS AB The internalization of DNA can be facilitated by adenovirus infection. Using the replication-deficient adenovirus, Ad-dl312, and a plasmid-based firefly luciferase gene as a reporter, we have optimized the uptake and expression of DNA in rat submandibular glands in vivo. Luciferase expression is transient and peaked at similar to 18 h after infection. Luciferase activity increased with plasmid concentration and was greatest at 10(9) to 10(10) plaque-forming units of Ad-dl312 per gland. We next examined the expression in vivo of plasmids containing deletions of the glutamine/glutamic acid-rich protein (GRP-Ca isoform) gene upstream region linked to a chloramphenicol acetyltransferase (CAT) reporter. Constructs with 9.4, 6.3, and 2.7 kb and 17 base pairs of upstream sequence gave relative CAT activities of 100, 30, 7.6, and 38.5, respectively. With the 9.4-kb GRP-Ca construct, CAT was preferentially expressed in acinar cells, which is characteristic of GRP. This gene transfer approach should prove useful in the further study of gene expression in salivary glands and other organs. C1 UNIV ROCHESTER, SCH MED, DEPT DENT RES, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, SCH MED, DEPT BIOCHEM, ROCHESTER, NY 14642 USA. RP OCONNELL, BC (reprint author), NIDR, CLIN INVEST & PATIENT CARE BRANCH, BLDG 10, BETHESDA, MD 20892 USA. NR 32 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1995 VL 268 IS 6 BP G1074 EP G1078 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA RF527 UT WOS:A1995RF52700025 ER PT J AU SHAH, AM SILVERMAN, HS GRIFFITHS, EJ SPURGEON, HA LAKATTA, EG AF SHAH, AM SILVERMAN, HS GRIFFITHS, EJ SPURGEON, HA LAKATTA, EG TI CGMP PREVENTS DELAYED RELAXATION AT REOXYGENATION AFTER BRIEF HYPOXIA IN ISOLATED CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE CARDIAC CONTRACTION; DIASTOLE; MYOFILAMENT; REPERFUSION ID IMPAIRED POSTHYPOXIC RELAXATION; INTRACELLULAR CALCIUM; MYOCARDIAL HYPOXIA; MUSCLE; CONTRACTION; PHOSPHATE; TENSION; FAILURE; RELEASE; FIBERS AB Previous studies in isolated cardiac myocytes suggest that impaired relaxation during reoxygenation after brief hypoxia results from abnormal Ca2+-myofilament interaction. Recent studies indicate that guanosine 3',5'-cyclic monophosphate (cGMP)-elevating interventions selectively enhance myocardial relaxation. We investigated the effect of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) on posthypoxic relaxation in single rat myocytes, with simultaneous measurement of contraction and intracellular Ca2+ (indo 1 fluorescence). In control myocytes (n = 11), reoxygenation after 10 min of hypoxia markedly prolonged time to peak shortening (+36.5 +/- 4.2%) and half-relaxation time (+75.7 +/- 11.3% cf. normoxic values; both P < 0.001) and reduced diastolic length but did not change cytosolic Ca2+. Under normoxic conditions, 50 mu M 8-BrcGMP slightly reduced time to peak shortening and half-relaxation time and increased diastolic length but did not alter cytosolic Ca2+. In the presence of 8-BrcGMP, there was no posthypoxic delay in twitch relaxation nor was there a decrease in diastolic length (half-relaxation time -5.8 +/- 3.3% cf. normoxic values; P < 0.05 cf. control group; n = 11). Cytosolic Ca2+ remained unaltered. Thus, 8-BrcGMP fully prevents impaired posthypoxic relaxation in isolated cardiac myocytes, probably by altering Ca2+-myofilament interaction. C1 JOHNS HOPKINS MED INST, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21218 USA. NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21218 USA. RP SHAH, AM (reprint author), UNIV WALES COLL CARDIFF, COLL MED, DEPT CARDIOL, HEATH PK, CARDIFF CF4 4XN, S GLAM, WALES. NR 30 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 1995 VL 268 IS 6 BP H2396 EP H2404 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RE373 UT WOS:A1995RE37300030 ER PT J AU BONNER, JC BRODY, AR AF BONNER, JC BRODY, AR TI CYTOKINE-BINDING PROTEINS IN THE LUNG SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Review DE GROWTH-PROMOTING CYTOKINES; TISSUE REPAIR; INFLAMMATORY LUNG DISEASE ID FIBROBLAST GROWTH-FACTOR; RECEPTOR-RELATED PROTEIN; NECROSIS-FACTOR-ALPHA; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; FACTOR CARRIER PROTEINS; HEPARIN-LIKE MOLECULES; HUMAN-SKIN FIBROBLASTS; FACTOR-BB ISOFORMS; FACTOR-BETA; ALPHA-2-MACROGLOBULIN RECEPTOR AB Numerous cytokines and growth factors signal the normal processes of tissue maintenance and remodeling in the lung, yet the aberrant expression of these peptide mediators is involved in a variety of pulmonary diseases. Furthermore, several different binding proteins function in controlling the extracellular levels of many of these cytokines in the lung. For example, a variety of cytokines and growth factors bind to and are regulated by the ubiquitous proteinase inhibitor, (alpha(2))-macroglobulin. The insulin-like growth factors are controlled by a specific class of six different insulin-like growth factor binding proteins. The transforming growth factor-beta family and fibroblast growth factors interact with extracellular matrix proteins. Several growth factor receptors are shed into the extracellular milieu where they retain a functional binding domain and thereby act as specific binding proteins. Cytokine-binding proteins appear to have a diversity of functions and may serve as extracellular cytokine reservoirs, protective shields against proteolytic degradation of cytokines, modifiers of cytokine-induced biological activity, or as clearance avenues for cytokines. The wide spectrum of cytokine-regulating molecules is important in cell-cell communications under normal conditions, whereas cytokine-binding protein dysfunction could contribute to a number of pulmonary diseases. C1 TULANE UNIV, MED CTR, DEPT PATHOL, LUNG BIOL PROGRAM, NEW ORLEANS, LA 70112 USA. RP BONNER, JC (reprint author), NIEHS, PULM PATHOBIOL LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 109 TC 31 Z9 32 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 1995 VL 268 IS 6 BP L869 EP L878 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA RM123 UT WOS:A1995RM12300002 PM 7541948 ER PT J AU HIRAMATSU, Y ECKELMAN, WC CARRASQUILLO, JA MILETICH, RS VALDEZ, IH KURRASCH, RHM MACYNSKI, AA PAIK, CH NEUMANN, RD BAUM, BJ AF HIRAMATSU, Y ECKELMAN, WC CARRASQUILLO, JA MILETICH, RS VALDEZ, IH KURRASCH, RHM MACYNSKI, AA PAIK, CH NEUMANN, RD BAUM, BJ TI KINETIC-ANALYSIS OF MUSCARINIC RECEPTORS IN HUMAN BRAIN AND SALIVARY-GLAND IN-VIVO SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE QUINUCLIDINYL IODOBENZILATE; PHARMACOKINETICS; MUSCARINIC-CHOLINERGIC RECEPTORS; HUMAN STUDIES ID POSITRON EMISSION TOMOGRAPHY; ACETYLCHOLINE-RECEPTORS; INACTIVE ENANTIOMERS; RAT-BRAIN; INVIVO; BINDING; QUANTIFICATION; CYCLOFOXY; TRANSPORT; SUBTYPES AB Previous studies in rats have suggested that the muscarinic acetylcholine receptor (mAChR) antagonist (S)-3-quinuclidinyl-(S)-4-[I-123]iodobenzilate [(SS)-IQNB] may be useful for the in vivo evaluation of mAChRs in humans as a control for the higher-affinity compound (RR)-IQNB. We have directly tested this hypothesis and examined the distribution of mAChRs in brain regions and parotid glands of healthy human volunteers in vivo using (RR)- and (SS)-IQNB (relatively high- and low-affinity antagonists, respectively), planar imaging, and pharmacokinetic analysis. This is the first in vivo study of mAChRs in humans that has employed stereoisomeric ligands and metabolic analysis to determine specific receptor binding. We observed that (SS)-IQNB showed much faster clearance from blood than (RR)-IQNB and different metabolite profiles. Also, the transport kinetics of the enantiomers were different. The estimated binding potential (similar to B-max/K-d) of (RR)-IQNB was highest in two cortical regions, intermediate in parotid gland, and lowest in cerebellum. The aggregate results show that in humans (SS)-IQNB does not act as an ideal general probe to measure the nonspecific IQNB distribution. However, (RR-) IQNB does appear to have value when used for studies of human brain mAChRs. C1 NIDR, DEPT NUCL MED, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. NIH, DEPT POSITRON EMISS TOMOG, BETHESDA, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 30 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD JUN PY 1995 VL 268 IS 6 BP R1491 EP R1499 PG 9 WC Physiology SC Physiology GA RE357 UT WOS:A1995RE35700020 ER PT J AU BURG, MB AF BURG, MB TI MOLECULAR-BASIS OF OSMOTIC REGULATION SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE SORBITOL; GLYCEROPHOSPHOCHOLINE; INOSITOL; TAURINE; BETAINE; ORGANIC OSMOLYTES ID ALDOSE REDUCTASE GENE; MEDULLARY COLLECTING DUCT; ORGANIC OSMOLYTE GLYCEROPHOSPHORYLCHOLINE; RENAL-CELLS; HYPEROSMOTIC STRESS; TAURINE TRANSPORT; EPITHELIAL-CELLS; MDCK CELLS; INOSITOL COTRANSPORTER; FUNCTIONAL EXPRESSION AB Cells almost universally respond to the stress of long-term hyperosmolality by accumulating compatible organic osmolytes. This allows them to maintain normal cell volume without a deleterious increase in intracellular inorganic ion concentration. Cells in the renal inner medulla are exposed to variable concentrations of salt and urea that may reach molal levels. The organic osmolytes that they accumulate include sorbitol, betaine, inositol, taurine, and glycerophosphocholine (GPC). This review considers recent advances in understanding osmotic regulation of these substances. Sorbitol is synthesized from glucose catalyzed by aldose reductase. Hypertonicity elevates the abundance of this enzyme by increasing transcription of its gene. Betaine is taken up via a specialized transporter. Hypertonicity raises the number of transporters by increasing their transcription. Current studies demonstrate that the 5' regions flanking the aldose reductase and betaine transporter genes contain osmotic response elements that increase transcription in response to hypertonicity. Osmotic regulation of inositol and taurine uptake also involves increased expression of specific transporter genes. GPC is unique in that its level rises in response to high urea, as well as hypertonicity. GPC accumulation is mainly regulated by changes in its degradation to choline, catalyzed by GPC:choline phosphodiesterase. Numerous other genes, including those for heat shock proteins, are also induced by hypertonicity. Their regulation and their role in osmotic regulation are the subject of considerable ongoing research. RP BURG, MB (reprint author), NHLBI, BLDG 10, RM 6N307, BETHESDA, MD 20892 USA. NR 95 TC 202 Z9 204 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD JUN PY 1995 VL 268 IS 6 BP F983 EP F996 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA RE356 UT WOS:A1995RE35600001 PM 7611465 ER PT J AU CHONG, SS KOZAK, CA LIU, LT KRISTJANSSON, K DUNN, ST BOURDEAU, JE HUGHES, MR AF CHONG, SS KOZAK, CA LIU, LT KRISTJANSSON, K DUNN, ST BOURDEAU, JE HUGHES, MR TI CLONING, GENETIC-MAPPING, AND EXPRESSION ANALYSIS OF A MOUSE RENAL SODIUM-DEPENDENT PHOSPHATE COTRANSPORTER SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE PROXIMAL TUBULE; NORTHERN ANALYSIS; IN SITU HYBRIDIZATION; REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION ID KIDNEY PROXIMAL TUBULES; BRUSH-BORDER MEMBRANES; PARATHYROID-HORMONE; PI TRANSPORT; OK CELLS; PROTEIN; REABSORPTION; CORTEX; CDNA; RAT AB Renal tubular reabsorption of phosphate is critical to the maintenance of phosphate homeostasis in mammals, and the brush-border membrane Na-P-i cotransport systems in proximal tubules play a major role in this process. We have isolated a cDNA encoding a mouse sodium-dependent phosphate transport protein (Npt1), which is expressed primarily in the kidney. This protein is highly similar to its human and rabbit homologues, based on nucleotide and amino acid comparisons. The presence of potential Asn-linked glycosylation and protein kinase C phosphorylation sites that are conserved among all three homologues suggests that these sites may be important in the function and regulation of this protein. The Npt1 gene was mapped to mouse chromosome 13, close to the Tcrg locus. By both in situ hybridization and reverse transcription-polymerase chain reaction, Npt1 mRNA was localized predominantly to the proximal tubule. C1 NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. UNIV OKLAHOMA, HLTH SCI CTR, OKLAHOMA CITY, OK 73104 USA. RI Chong, Samuel/D-8098-2015 NR 34 TC 48 Z9 48 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD JUN PY 1995 VL 268 IS 6 BP F1038 EP F1045 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA RE356 UT WOS:A1995RE35600007 ER PT J AU GOLDBERG, TE GOLD, JM TORREY, EF WEINBERGER, DR AF GOLDBERG, TE GOLD, JM TORREY, EF WEINBERGER, DR TI LACK OF SEX-DIFFERENCES IN THE NEUROPSYCHOLOGICAL PERFORMANCE OF PATIENTS WITH SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MONOZYGOTIC TWINS DISCORDANT; GENDER DIFFERENCES; VENTRICULAR ENLARGEMENT; AFFECTIVE-DISORDERS; SYMPTOMATOLOGY; AGE AB Objective: While a number of studies have suggested that women with schizophrenia have a less severe form of the disorder than men, the issue has been examined with neuropsychological measures only infrequently. Method: The authors compared neuropsychological test performances of men and women from four independent schizophrenic cohorts: two groups of inpatients with chronic courses at a research hospital (N=228 and N=63), one group of consecutive admissions to a private psychiatric hospital (N=57), and one group of schizophrenic twins from discordant monozygotic pairs (N=20). Nearly 100 comparisons of neuropsychological test performances were made between melt and women. Results: Not one comparison significantly favored women, and few were even significantly different between the sexes. Conclusions: It cannot be ruled out that the disproportionate number of men in the chronic cohorts may have reflected either more frequent intellectual deterioration in men or a bias toward more severely impaired women. Yet, men and women in all groups performed similarly, including the groups in which the sex ratios were nearly equal and were not skewed toward chronicity. These results provide little support for the hypothesis that gender is associated with a unique pathogenesis of schizophrenia or is a marker for a distinct subtype of schizophrenia, at least to the extent that cognitive impairment is a primary manifestation of the underlying disease process. However, given the lack of female patients with later ages at onset and more affective symptoms, the results in this study should be considered relevant only for chronic patients with onset of schizophrenia before age 30. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC. RP GOLDBERG, TE (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,2700 MARTIN LUTHER KING JR AVE,SE,WASHINGTON,DC 20032, USA. NR 39 TC 67 Z9 68 U1 2 U2 2 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 JUN PY 1995 VL 152 IS 6 BP 883 EP 888 PG 6 WC Psychiatry SC Psychiatry GA RC494 UT WOS:A1995RC49400011 PM 7755118 ER PT J AU MEHLMAN, PT HIGLEY, JD FAUCHER, I LILLY, AA TAUB, DM VICKERS, J SUOMI, SJ LINNOILA, M AF MEHLMAN, PT HIGLEY, JD FAUCHER, I LILLY, AA TAUB, DM VICKERS, J SUOMI, SJ LINNOILA, M TI CORRELATION OF CSF 5-HIAA CONCENTRATION WITH SOCIALITY AND THE TIMING OF EMIGRATION IN FREE-RANGING PRIMATES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID MONOAMINE; OBSESSIVE-COMPULSIVE DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; RHESUS-MONKEYS; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; HOMOVANILLIC-ACID; ANOREXIA-NERVOSA; MACACA-SYLVANUS; VERVET MONKEYS AB Objective: The purpose of this study was to examine the relationship between behavior and serotonin in nonhuman primates. Method: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Blood samples (N=23) and CSF samples (N=22) were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. Results: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration was positively correlated with three measures of sociality: 1) total time spent grooming others, 2) total time spent in close proximity to other group members, and 3) mean number of neighbors within a 5-m radius. In addition, CSF 5-HIAA concentration was positively correlated with age at emigration from the natal group (in months). Conclusions: In adolescent male rhesus macaques living in naturalistic settings, CSF 5-HIAA concentration is positively correlated with affiliative sociality. Rhesus males with low CSF 5-HIAA concentrations exhibit less social competence and emigrate from their social groups at a younger age than do males with higher concentrations of CSF 5-HIAA. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BETHESDA,MD 20892. RP MEHLMAN, PT (reprint author), LAB ANIM BREEDERS & SERV INC,POB 557,YEMASSEE,SC 29945, USA. FU PHS HHS [223-89-1101] NR 62 TC 129 Z9 129 U1 4 U2 14 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 JUN PY 1995 VL 152 IS 6 BP 907 EP 913 PG 7 WC Psychiatry SC Psychiatry GA RC494 UT WOS:A1995RC49400015 PM 7538731 ER PT J AU JANERICH, DT HADJIMICHAEL, O SCHWARTZ, PE LOWELL, DM MEIGS, JW MERINO, MJ FLANNERY, JT POLEDNAK, AP AF JANERICH, DT HADJIMICHAEL, O SCHWARTZ, PE LOWELL, DM MEIGS, JW MERINO, MJ FLANNERY, JT POLEDNAK, AP TI THE SCREENING HISTORIES OF WOMEN WITH INVASIVE CERVICAL-CANCER, CONNECTICUT SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. Methods. All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). Results. Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. Conclusions. Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings. C1 FDN BLOOD RES,SCARBOROUGH,ME 04074. YALE UNIV,NEW HAVEN,CT. NCI,BETHESDA,MD 20892. CONNECTICUT DEPT PUBL HLTH & ADDICT SERV,HARTFORD,CT. RP JANERICH, DT (reprint author), UNIV UTAH,SCH MED,DEPT MED,50 N MED DR,SALT LAKE CITY,UT 84132, USA. FU NCI NIH HHS [CA42101, CA42014] NR 12 TC 165 Z9 165 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSN 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 JUN PY 1995 VL 85 IS 6 BP 791 EP 794 DI 10.2105/AJPH.85.6.791 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA317 UT WOS:A1995RA31700009 PM 7762711 ER PT J AU HOUN, F HELZLSOUER, KJ FRIEDMAN, NB STEFANEK, ME AF HOUN, F HELZLSOUER, KJ FRIEDMAN, NB STEFANEK, ME TI THE PRACTICE OF PROPHYLACTIC MASTECTOMY - A SURVEY OF MARYLAND SURGEONS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BREAST-CANCER; OVARIAN-CANCER; GEOGRAPHIC-VARIATION; RISK; PREVENTION; WOMEN AB Objectives. Bilateral prophylactic mastectomy is a drastic breast cancer preventive option for which indications are not standardized and efficacy has not been proven. To estimate the magnitude of this controversial practice, surgeons were surveyed on their recommendations about and performance of prophylactic mastectomy. Methods. A cross-sectional survey was sent to general surgeons (n = 522), plastic surgeons (n = 80), and gynecologists (n = 801) licensed to practice in Maryland in 1992. Proportions responding were 41.9%, 66.3%, and 54.9%, respectively. In addition, there were 30 respondents who identified ''other'' as their specialty. The respondents were asked about the role of bilateral prophylactic mastectomy and the number of times they had recommended and performed it in a year. Results. Seven hundred forty-two surgeons responded (51.8%). More plastic surgeons (84.6%) than general surgeons (47.0%) and gynecologists (38.3%) agreed that bilateral prophylactic mastectomy has a role in the care of high-risk women. Eighty-one percent of plastic surgeons had recommended the procedure, compared with 38.8% of general surgeons and 17.7% of gynecologists. Conclusions. Indications and practice patterns reveal heterogeneity of medical opinion and practice of prophylactic mastectomy. This study raises the need for better evaluation of the efficacy and appropriateness of prophylactic mastectomy. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DEPT SURG,BALTIMORE,MD. NR 33 TC 34 Z9 34 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSN 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 JUN PY 1995 VL 85 IS 6 BP 801 EP 805 DI 10.2105/AJPH.85.6.801 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA317 UT WOS:A1995RA31700011 PM 7762713 ER PT J AU HEFFNER, JE BROWN, LK BARBIERI, C DELEO, JM AF HEFFNER, JE BROWN, LK BARBIERI, C DELEO, JM TI PLEURAL FLUID CHEMICAL-ANALYSIS IN PARAPNEUMONIC EFFUSIONS - A METAANALYSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PH; MANAGEMENT; GLUCOSE AB Controversy exists regarding the clinical utility of pleural fluid pH, lactate dehydrogenase (LDH), and glucose for identifying complicated parapneumonic effusions that require drainage. in this report, we performed a meta-analysis of pertinent studies, using receiver operating characteristic (ROC) techniques, to assess the diagnostic accuracy of these tests, to determine appropriate decision thresholds, and to evaluate the quality of the primary studies. Seven primary studies reporting values for pleural fluid pH (n = 251), LDH (0 = 114), or glucose (n = 135) in pneumonia patients were identified. We found that pleural fluid pH had the highest diagnostic accuracy for all patients with parapneumonic effusions as measured by the area under the ROC curve (AUG = 0.92) compared with pleural fluid glucose (AUG = 0.84) or LDH (AUG = 0.82). After excluding patients with purulent effusions, pH (AUG = 0.89) retained the highest diagnostic accuracy. pleural fluid pH decision thresholds varied between 721 and 7.29 depending on cost-prevalence considerations. The quality of the primary stud ies was the major limitation in determining the value of plural fluid chemical analysis. We conclude that meta-analysis of the available data refines the application of pleural fluid chemical analysis but a clearer understanding of the usefulness of these tests awaits more rigorous primary investigations. C1 UNIV ARIZONA,HLTH SCI CTR,TUCSON,AZ. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP HEFFNER, JE (reprint author), UNIV ARIZONA,HLTH SCI CTR,ST JOSEPH HOSP & MED CTR,DEPT MED,350 W THOMAS RD,PHOENIX,AZ 85001, USA. NR 35 TC 145 Z9 147 U1 0 U2 4 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1995 VL 151 IS 6 BP 1700 EP 1708 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RB346 UT WOS:A1995RB34600002 PM 7767510 ER PT J AU BURCHFIEL, CM MARCUS, EB CURB, JD MACLEAN, CJ VOLLMER, WM JOHNSON, LR FONG, KO RODRIGUEZ, BL MASAKI, KH BUIST, AS AF BURCHFIEL, CM MARCUS, EB CURB, JD MACLEAN, CJ VOLLMER, WM JOHNSON, LR FONG, KO RODRIGUEZ, BL MASAKI, KH BUIST, AS TI EFFECTS OF SMOKING AND SMOKING CESSATION ON LONGITUDINAL DECLINE IN PULMONARY-FUNCTION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FORCED EXPIRATORY VOLUME; CORONARY HEART-DISEASE; JAPANESE-AMERICAN MEN; AIR-FLOW OBSTRUCTION; CIGARETTE-SMOKING; LUNG-FUNCTION; FOLLOW-UP; ONE 2ND; SPIROMETRY; ADULTS AB Effects of cigarette smoking and smoking cessation on rate of FEV(1) decline over 6 yr were examined in 4,451 Japanese-American men from the Honolulu Heart Program who were 45 to 68 yr of age at baseline (1965-1968). Within-person regression was used to calculate annual change in FEV(1). Rates of FEV(1) decline varied strongly with smoking status and increased significantly with age. Overall, men who continued to smoke experienced steeper rates of decline compared with men who never smoked (-33 ml/yr versus -22 ml/yr, respectively; p = 0.0001). Rates of decline for those who quit smoking during the first 2 yr (-32 ml/yr) were nearly the same as those who continued smoking (-34 ml/yr). After quitting, their rates of decline diminished to a level (-19 ml/yr) similar to that of men who had never smoked (-21 ml/yr). FEV(1) decline in continuing smokers was significantly associated with duration of smoking, whereas associations with intensity and pack-years were of borderline significance. Among 216 men with impaired pulmonary function, those who quit smoking had significantly slower rates of FEV(1) decline than did those who continued smoking. Potential reasons for quitting included respiratory conditions and stroke. These results extend previous reports of accelerated rates of FEV(1) decline in the persons who continue to smoke, and they indicate that smoking cessation leads to less steep rates of decline in pulmonary function over a short period of time in middle-aged men, as well as in men with established pulmonary impairment. C1 UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. OREGON HLTH SCI UNIV,SCH MED,PORTLAND,OR. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. RP BURCHFIEL, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 35 TC 100 Z9 103 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1995 VL 151 IS 6 BP 1778 EP 1785 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RB346 UT WOS:A1995RB34600013 PM 7767520 ER PT J AU KAWANAMI, O JIANG, HX MOCHIMARU, H YONEYAMA, H KUDOH, S OHKUNI, H OOAMI, H FERRANS, VJ AF KAWANAMI, O JIANG, HX MOCHIMARU, H YONEYAMA, H KUDOH, S OHKUNI, H OOAMI, H FERRANS, VJ TI ALVEOLAR FIBROSIS AND CAPILLARY ALTERATION IN EXPERIMENTAL PULMONARY SILICOSIS IN RATS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FIBROTIC LUNG DISORDERS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; GROWTH-FACTOR; GAS-EXCHANGE; DIFFERENTIATION; ULTRASTRUCTURE; PROLIFERATION; ANGIOGENESIS; PNEUMONITIS AB To analyze the evolution of fibrotic and vascular changes in pulmonary silicosis, ultrastructural and immunohistochemical studies were made of the lungs of rats given a single intratracheal injection of silica particles. Early lesions were characterized by accumulations of macrophages and neutrophils in alveolar lumina and interstitium and by damage to alveolar capillaries and epithelial cells. The intraluminal masses of inflammatory cells developed into granulomas and became associated with myofibroblasts that migrated from the interstitium through the damaged epithelial lining. Type II epithelial cells and bronchiolar cuboidal cells proliferated rapidly to line the intraluminal granulomas, incorporating them into the interstitium. This process mediated the transition from intraalveolar fibrosis to interstitial fibrosis. Vascular damage was repaired by proliferation and migration of endothelial cells. Some endothelial cells in alveolar capillaries expressed Factor VIII-related antigen at 2 wk after silica infusion. In normal animals, this feature was present in peribronchiolar but not in alveolar capillaries. Two patterns of endothelial cell migration were shown by staining for proliferating-cell nuclear antigen. The first pattern was characterized by endothelial cells that extended their cytoplasm over preexisting, denuded basement membranes and replaced necrotic cells in alveolar capillaries. At 4 mo after injury, some of these cells had developed fenestrations. The second pattern consisted of budlike sproutings that developed only in peribronchiolar connective tissue. These observations indicate that peribronchiolar vessels are sources for renewal of alveolar capillary endothelium as well as for neovascularization. C1 SHANGHAI INST OCCUPAT DIS,SHANGHAI,PEOPLES R CHINA. NIPPON MED COLL,DEPT MED,TOKYO,JAPAN. NIPPON MED COLL,INST GERONTOL,DIV IMMUNOL,KAWASAKI,KANAGAWA,JAPAN. NIPPON MED COLL,INST GERONTOL,DIV PATHOL,KAWASAKI,KANAGAWA,JAPAN. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP KAWANAMI, O (reprint author), NIPPON MED COLL,HOSP 2,PATHOL & CLIN RES LAB,NAKAHARA KU,KOSUGI CHO 1-396,KAWASAKI,KANAGAWA 211,JAPAN. NR 35 TC 26 Z9 27 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1995 VL 151 IS 6 BP 1946 EP 1955 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RB346 UT WOS:A1995RB34600038 PM 7767544 ER PT J AU MOSSMAN, BT MASON, R MCDONALD, JA GAIL, DB AF MOSSMAN, BT MASON, R MCDONALD, JA GAIL, DB TI ADVANCES IN MOLECULAR-GENETICS, TRANSGENIC MODELS, AND GENE-THERAPY FOR THE STUDY OF PULMONARY-DISEASES SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RECOMBINATION; EXPRESSION; GROWTH C1 NHLBI,DIV LUNG DIS,LUNG BIOL & DIS PROGRAM,BETHESDA,MD 20892. NR 8 TC 7 Z9 8 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1995 VL 151 IS 6 BP 2065 EP 2069 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RB346 UT WOS:A1995RB34600052 PM 7767558 ER PT J AU SIMEONOVA, PP LUSTER, MI AF SIMEONOVA, PP LUSTER, MI TI IRON AND REACTIVE OXYGEN SPECIES IN THE ASBESTOS-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA RESPONSE FROM ALVEOLAR MACROPHAGES SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; CROCIDOLITE ASBESTOS; PULMONARY FIBROSIS; HYDROGEN-PEROXIDE; CYTOKINE RELEASE; MESSENGER-RNA; FREE-RADICALS; EXPOSURE; DISEASES; HYDROXYL AB Free radicals and other reactive oxygen species (ROS) are important mediators in asbestos-induced lung toxicity. Asbestos fibers are thought to stimulate cells to generate ROS via iron that is present on fibrous silicates. The pathophysiologic responses in the lung after asbestos exposure are characterized by the accumulation of macrophages at the site of fiber deposition and the release of growth factors and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We have examined the role of iron-catalyzed ROS in asbestos induction of TNF-alpha from rat alveolar macrophages. Treatment of alveolar macrophage cultures with asbestos stimulated dose-dependently TNF-alpha, secretion, which was inhibited by the addition of deferoxamine, an iron chelator. Asbestos fibers, pretreated with deferoxamine to remove iron from the fibers before addition to alveolar macrophages, also significantly reduced the TNF-alpha response. Consistent with the role of iron on asbestos fibers in catalyzing hydroxyl radical generation, membrane-permeable hydroxyl radical scavengers (tetramethylthiourea, dimethyl sulfoxide) inhibited the asbestos-induced TNF-alpha response. The asbestos-induced increase in TNF-alpha, as well as in interleukin-1 alpha, and their inhibition by tetramethylthiourea occurred at the transcriptional level. The role of ROS in signaling TNF-alpha stimulation was confirmed by use of free radical-generating systems (hypoxanthine-xanthine oxidase, hydrogen peroxide, glucose-glucose oxidase, or ferrous plus hydrogen peroxide). These results suggest that intracellularly generated ROS can stimulate TNF-alpha in alveolar macrophages and that asbestos-induced TNF-alpha gene expression and secretion are mediated by iron-catalyzed production of ROS. RP SIMEONOVA, PP (reprint author), NIEHS, ENVIRONM IMMUNOL & NEUROBIOL SECT, MD CL-04, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 40 TC 109 Z9 111 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1995 VL 12 IS 6 BP 676 EP 683 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA RA618 UT WOS:A1995RA61800013 PM 7539275 ER PT J AU PLOWE, CV DJIMDE, A BOUARE, M DOUMBO, O WELLEMS, TE AF PLOWE, CV DJIMDE, A BOUARE, M DOUMBO, O WELLEMS, TE TI PYRIMETHAMINE AND PROGUANIL RESISTANCE-CONFERRING MUTATIONS IN PLASMODIUM-FALCIPARUM DIHYDROFOLATE-REDUCTASE - POLYMERASE CHAIN-REACTION METHODS FOR SURVEILLANCE IN AFRICA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID THYMIDYLATE SYNTHASE GENE; MOLECULAR-BASIS; MALARIA; CYCLOGUANIL; VIVAX AB As chloroquine resistance spreads across Africa, the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and proguanil are being used as alternative first-line drugs for the treatment and prevention of Plasmodium falciparum malaria. Resistance to these drugs is conferred by point mutations in parasite DHFR. These point mutations can be detected by polymerase chain reaction (PCR) assays, but better methods for sample collection, DNA extraction, and a diagnostic PCR are needed to make these assays useful in malaria-endemic areas. Here we report methods for collecting fingerstick blood onto filter paper strips that are air-dried, then stored and transported at room temperature. Cell lysis and DNA extraction are accomplished by boiling in Chelex-100. We also report a nested PCR technique that has improved sensitivity and specificity. These procedures readily detect mixed infections of parasites with both sensitive and resistant genotypes (confirmed by direct sequencing) and are reliable at parasite densities less than 250/mm(3) in field surveys. C1 NATL SCH MED & PHARM,CTR MALARIA RES & TRAINING,BAMAKO,MALI. RP PLOWE, CV (reprint author), NIAID,PARASIT DIS LAB,MALARIA GENET SECT,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 14 TC 362 Z9 367 U1 1 U2 6 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 JUN PY 1995 VL 52 IS 6 BP 565 EP 568 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA RK696 UT WOS:A1995RK69600018 PM 7611566 ER PT J AU HIGUCHI, K SHIMADA, A HOSOKAWA, M TAKEDA, T AF HIGUCHI, K SHIMADA, A HOSOKAWA, M TAKEDA, T TI THE FIRST INTERNATIONAL-CONFERENCE ON SENESCENCE - THE SAM MODEL - KYOTO, JAPAN, 1994 SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Editorial Material DE SENESCENCE-ACCELERATED MOUSE (SAM); ANIMAL MODEL; AGING; AGE-ASSOCIATED DISORDERS; AMYLOIDOSIS; NEUROSCIENCE C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. RP HIGUCHI, K (reprint author), KYOTO UNIV,CHEST DIS RES INST,DEPT SENESCENCE BIOL,SAKYO KU,KYOTO 606,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE, ENGLAND LA6 2LA SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD JUN PY 1995 VL 2 IS 2 BP 134 EP 138 DI 10.3109/13506129509031900 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA RH493 UT WOS:A1995RH49300010 ER PT J AU POSTON, JM AF POSTON, JM TI THE ANAEROBIC CHAMBER AT THE NATIONAL-INSTITUTE-OF-HEALTH SO ANAEROBE LA English DT Letter RP POSTON, JM (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN PY 1995 VL 1 IS 3 BP 183 EP 184 DI 10.1006/anae.1995.1017 PG 2 WC Microbiology SC Microbiology GA RV866 UT WOS:A1995RV86600007 PM 16887526 ER PT J AU NEWBURY, DE SWYT, CR MYKLEBUST, RL AF NEWBURY, DE SWYT, CR MYKLEBUST, RL TI STANDARDLESS QUANTITATIVE ELECTRON-PROBE MICROANALYSIS WITH ENERGY-DISPERSIVE X-RAY SPECTROMETRY - IS IT WORTH THE RISK SO ANALYTICAL CHEMISTRY LA English DT Article AB ''Standardless'' procedures for quantitative electron probe X-ray microanalysis attempt to eliminate the need for standardization through calculation of standard (pure element) intensities, Either ''first principles'' calculations, which account for all aspects of X-ray generation, propagation, and detection, or ''fitted standards'' calculations, which use mathematical fits to measured intensities from a limited set of pure standards, can form the basis for standardless analysis, The first principles standardless analysis procedure embedded in the National Institutes of Health/National Institute of Standards and Technology comprehensive X-ray calculation engine and database, Desktop Spectrum Analyzer, has been tested against spectra measured on MST standard reference materials, research materials, and binary compounds, The resulting distribution of errors is broad, ranging from -90% to +150% relative, First principles standardless analysis can thus lead to unacceptably large errors. C1 NIH,BETHESDA,MD 20892. RP NEWBURY, DE (reprint author), NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899, USA. NR 15 TC 30 Z9 30 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 1 PY 1995 VL 67 IS 11 BP 1866 EP 1871 DI 10.1021/ac00107a017 PG 6 WC Chemistry, Analytical SC Chemistry GA RA091 UT WOS:A1995RA09100021 PM 9306735 ER PT J AU MORIKAWA, H KATO, K KIMOTO, H COHEN, LA AF MORIKAWA, H KATO, K KIMOTO, H COHEN, LA TI CRYSTAL-STRUCTURE OF 2-METHOXY-2-(TRIFLUOROMETHYL)TETRAHYDROIMIDAZOLE-4,5-DIONE SO ANALYTICAL SCIENCES LA English DT Note C1 NIDDKD,BETHESDA,MD 20892. RP MORIKAWA, H (reprint author), NATL IND RES INST NAGOYA,HIRATE CHO,NAGOYA,AICHI 462,JAPAN. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JAPAN SOC ANALYTICAL CHEM PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD JUN PY 1995 VL 11 IS 3 BP 465 EP 466 DI 10.2116/analsci.11.465 PG 2 WC Chemistry, Analytical SC Chemistry GA RD292 UT WOS:A1995RD29200023 ER PT J AU ABBOTT, LC JACOBOWITZ, DM AF ABBOTT, LC JACOBOWITZ, DM TI DEVELOPMENT OF CALRETININ-IMMUNOREACTIVE UNIPOLAR BRUSH-LIKE CELLS AND AN AFFERENT PATHWAY TO THE EMBRYONIC AND EARLY POSTNATAL MOUSE CEREBELLUM SO ANATOMY AND EMBRYOLOGY LA English DT Article DE CALCIUM-BINDING PROTEIN; IMMUNOCYTOCHEMISTRY; PALE CELLS; HOOK BUNDLE OF RUSSELL; UNIPOLAR BRUSH CELLS ID CALCIUM-BINDING PROTEIN; RAT NERVOUS-SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; PURKINJE-CELLS; NEURONS; BRAIN; CORTEX; ORIGIN; CALBINDIN-D28K; PARVALBUMIN AB In the developing mouse hindbrain, immunoreactivity for calretinin, a calcium-binding protein, was first observed at embryonic day 10, and was localized to neuronal cell bodies in the reticular formation. By embryonic day 12, fibers emanated rostrally from the calretinin-immunoreactive neurons, extended dorsally and then caudally in the uncinate fasciculus to reach the developing cerebellar plate. These fibers crossed the cerebellar midline and were distributed to the contralateral side of the cerebellum. The number and intensity of staining of cell bodies in the reticular formation was reduced in postnatal mice. After postnatal day 1, it was no longer possible to discern the calretinin-immunoreactive fiber bundle in the brainstem, although fibers were still visible at the level of the uncinate fasciculus and in the cerebellum. We also observed intensely calretinin-immunoreactive, smaller cells in the cerebellum (embryonic day 14) and dorsal cochlear nuclei (embryonic day 18), most of which we believe are destined to become the ''unipolar brush'', (also known as ''pale'' or ''monodendritic'') cells observed in the adult mammalian brain. An immature form of these cells exists in the developing mouse cerebellum. Thus, using calretinin antiserum as a market; an afferent neuronal system was described which projects to the cerebellar primordium. It is suggested that the calretinin-containing hook bundle is an afferent projection which provides a feed-forward neuronal system to the cerebellum which, in turn, projects afferent fibers to the calrelinin-containing and other cells of the reticular formation. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT VET BIOSCI,URBANA,IL 61801. NR 56 TC 49 Z9 49 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD JUN PY 1995 VL 191 IS 6 BP 541 EP 559 PG 19 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA QZ535 UT WOS:A1995QZ53500006 PM 7677260 ER PT J AU HENGGE, UR BROCKMEYER, NH AF HENGGE, UR BROCKMEYER, NH TI MEGESTROL FOR AIDS-RELATED ANOREXIA SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 UNIV ESSEN GESAMTHSCH,ESSEN,GERMANY. RP HENGGE, UR (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 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 JUN 1 PY 1995 VL 122 IS 11 BP 879 EP 879 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RA139 UT WOS:A1995RA13900013 PM 7741375 ER PT J AU DALAKAS, MC ILLA, I AF DALAKAS, MC ILLA, I TI COMMON VARIABLE IMMUNODEFICIENCY AND INCLUSION-BODY MYOSITIS - A DISTINCT MYOPATHY MEDIATED BY NATURAL-KILLER-CELLS SO ANNALS OF NEUROLOGY LA English DT Note ID POLYMYOSITIS; DERMATOMYOSITIS; EXPRESSION AB Inclusion body myositis developed in two men, 36 and 48 years old with long-standing common variable immunodeficiency. Immunophenotypic analysis of the endomysial cells showed an increased number of natural killer (NK) cells (defined as CD57(+), CD56(+), CD3(-), CD8(-), CD68(-)) accounting for 8.5 to 9.5% of the total cells, compared with a mean of 1% in sporadic inclusion body myositis. The remaining cells were CD8(+) macrophages, and CD4(+) T cells. NK cells were positive for intercellular cell adhesion molecule-1 and invaded muscle fibers negative for major histocompatibility complex (MHC) class 1. In contrast to ubiquitous endomysial expression of MHC class I antigen in sporadic inclusion body myositis, the MHC class I in common variable immunodeficiency and inclusion body myositis was absent or weakly expressed in only some of the muscle fibers surrounded by CD8(+) cells. Enteroviral or retroviral RNA sequences were not amplified. Treatment with intravenous immunoglobulin improved strength in 1 patient whose repeated muscle biopsy specimen showed normal NK cells. We conclude that inclusion body myositis can develop in patients with common variable immunodeficiency. Common variable Immunodeficiency with inclusion body myositis is an immune myopathy mediated by NK cells in a non-MHC class I-restricted cytotoxicity, and by CD8(+) cells in an MHC class I-restricted process. This is the first description of an inflammatory myopathy in which NK cells participate in the myocytotoxic process. RP DALAKAS, MC (reprint author), NINCDS,MED NEUROL BRANCH,BLDG 10,ROOM 4N-248,10 CTR DR,MSC 1382,BETHESDA,MD 20892, USA. NR 16 TC 28 Z9 29 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 JUN PY 1995 VL 37 IS 6 BP 806 EP 810 DI 10.1002/ana.410370615 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RD040 UT WOS:A1995RD04000014 PM 7778855 ER PT J AU XU, JL YANG, GL AF XU, JL YANG, GL TI A NOTE ON A CHARACTERIZATION OF THE EXPONENTIAL-DISTRIBUTION BASED ON A TYPE-II CENSORED SAMPLE SO ANNALS OF STATISTICS LA English DT Article DE CHARACTERIZATION; EXPONENTIAL DISTRIBUTION; TYPE II RIGHT-CENSORED ID ORDER-STATISTICS AB Let X((1)) less than or equal to X((2)) less than or equal to ...less than or equal to X((n)) be the order statistics of a random sample of n lifetimes. The total-time-on-test statistic at X((i)) is defined by S-i,S-n = Sigma(j=1)(i)(n - j + 1)(X((j)) - X((j-1))), 1 less than or equal to i less than or equal to n. A type II censored sample is composed of the r smallest observations and the remaining n - r Lifetimes which are known only to be at least as large as X((r)). Dufour conjectured that if the vector of proportions (S-1,S-n/S-r,S-n,...,S-r-1,S-n/S-r,S-n) has the distribution of the order statistics of r - 1 uniform(0, 1) random variables, then X(1) has an exponential distribution. Leslie and van Eeden proved the conjecture provided n - r is no larger than (1/3)n - 1. It is shown in this note that the conjecture is true in general for n greater than or equal to r greater than or equal to 5. If the random variable under consideration has either NBU or NWU distribution, then it is true for n greater than or equal to r greater than or equal to 2, n greater than or equal to 3. The lower bounds obtained here do not depend on the sample size. C1 UNIV MARYLAND,DEPT MATH,COLLEGE PK,MD 20742. RP XU, JL (reprint author), NCI,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD JUN PY 1995 VL 23 IS 3 BP 769 EP 773 DI 10.1214/aos/1176324621 PG 5 WC Statistics & Probability SC Mathematics GA RR003 UT WOS:A1995RR00300005 ER PT J AU TEMECK, BK WEXLER, LH STEINBERG, SM MCCLURE, LL HOROWITZ, M PASS, HI AF TEMECK, BK WEXLER, LH STEINBERG, SM MCCLURE, LL HOROWITZ, M PASS, HI TI METASTASECTOMY FOR SARCOMATOUS PEDIATRIC HISTOLOGIES - RESULTS AND PROGNOSTIC FACTORS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 02, 1995 CL PALM SPRINGS, CA SP Soc Thorac Surgeons ID SOFT-TISSUE SARCOMA; METASTATIC OSTEOGENIC-SARCOMA; PULMONARY METASTASES; MEDIAN STERNOTOMY; RESECTION; THORACOTOMY; SURVIVAL; INDICATORS AB We reviewed our experience of pediatric metastasectomy to define (I) morbidity/mortality in this population and (2) any preoperative or intraoperative prognostic predictors of survival. One hundred fifty-two patients with median age 19 years (range, 5 to 33 years) had 258 thoracic explorations (Ewing's sarcoma, 28; rhabdomyosarcoma, 6; nonrhabdomyosarcoma soft tissue sarcoma, 42; and osteosarcoma, 76). Resections were accomplished by 218 wedge resections, 19 anatomic resections, 14 wedge and anatomic resections, 4 wedge and chest wall resections, and 3 wedge resections/other procedures. An initial complete resection was accomplished in 121/152 patients (80%), With a median potential follow-up of 10.6 years, median survival from initial thoracotomy is 2.2 years. By the Cox proportional hazards model, three or more positive nodules (p = 0.021), histology other than osteosarcoma (p = 0.0054) and incomplete resection (p < 0.0001) were unfavorable prognostic factors for survival. Two or more positive nodules (p = 0.0049), left location (p = 0.0031), age 14 years or greater at diagnosis (p = 0.0052), or rhabdomyosarcoma (p = 0.0066) predicted shorter pulmonary progression-free survivals after resection. Nonrhabdomyosarcoma pediatric metastasectomy can yield selected long-term survival. Morbidity/mortality is low and a complete resection, if possible, is paramount; Prognostic factors can be defined that can be used to define the limits of this therapy to the patient and family. C1 NCI,THORAC ONCOL SECT,SURG BRANCH,BETHESDA,MD 20892. NCI,PEDIAT ONCOL SECT,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NR 31 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1995 VL 59 IS 6 BP 1385 EP 1390 DI 10.1016/0003-4975(95)00233-B PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA RB621 UT WOS:A1995RB62100007 PM 7771815 ER PT J AU PETTIT, GR TEMPLE, C NARAYANAN, VL VARMA, R SIMPSON, MJ BOYD, MR RENER, GA BANSAL, N AF PETTIT, GR TEMPLE, C NARAYANAN, VL VARMA, R SIMPSON, MJ BOYD, MR RENER, GA BANSAL, N TI ANTINEOPLASTIC AGENTS-322 - SYNTHESIS OF COMBRETASTATIN A-4 PRODRUGS SO ANTI-CANCER DRUG DESIGN LA English DT Article DE COMBRETASTATIN A-4 PRODRUG ID INHIBITOR; TUBULIN AB Combretastatin A-4 (1a), the principal cancer cell growth-inhibitory constituent of the Zulu medicinal plant Combretum caffrum, has been undergoing preclinical development. However, the very limited water solubility of this phenol has complicated drug formation. Hence, derivatives of the combretastatin A-4 (1a) 3'-phenol group were prepared for evaluation as possible water-soluble prodrugs. As observed for combretastatin A-4, the sodium salt (1b), potassium salt (1c) and hemi-succinic acid ester (1e) derivatives of phenol 1a were essentially insoluble in water. Indeed, these substances regenerated combretastatin A-4 upon reaction with water. A series of other simple derivatives (1d, 1f-j) proved unsatisfactory in terms of water solubility or stability, or both. The most soluble derivatives evaluated included the ammonium (1l), potassium (1m) and sodium (1n) phosphate salts, where the latter two proved most stable and suitable. Both the potassium (1m) and sodium (1n) phosphate derivatives of combretastatin A-4 were also found to exhibit the requisite biological properties necessary for a useful prodrug. Sodium salt 1n was selected for drug formulation and further pre-clinical development. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. SO RES INST,ORGAN CHEM RES LABS,BIRMINGHAM,AL 35255. NCI,DIV CANC TREATMENT,DRUG SYNTHESIS & CHEM BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DCT,DTP,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,BOX 871604,TEMPE,AZ 85287, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA44344-01A1-06, N01-CM-87229] NR 19 TC 219 Z9 225 U1 3 U2 12 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD JUN PY 1995 VL 10 IS 4 BP 299 EP 309 PG 11 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA RH647 UT WOS:A1995RH64700002 PM 7786396 ER PT J AU NARUKI, Y MALONEY, PJ REYNOLDS, JC LARSON, SM CARRASQUILLO, JA AF NARUKI, Y MALONEY, PJ REYNOLDS, JC LARSON, SM CARRASQUILLO, JA TI SELECTIVE CYTOTOXICITY OF Y-90 LABELED T101 MONOCLONAL-ANTIBODY ON HUMAN-MALIGNANT T-CELL LINES SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article ID RADIOIMMUNOTHERAPY; RADIONUCLIDES; LYMPHOMA; IN-111; RADIOIMMUNODETECTION; LYMPHOCYTES; TOXICITY; PROTEIN AB Yttrium-90 radiolabeled antibodies are currently being evaluated as radioimmunotherapeutic reagents. In this study we evaluated whether Y-90 labeled T101, a murine IgG2a monoclonal antibody (MoAb) that recognizes CD5 could selectively induce cytotoxic damage to cells in culture. Two CD5 positive cell lines, HUT102 and CCRF-CEM cells and PGT a CD5 negative cell line was treated with 0.005 to 5 mu Ci of Y-90 T101. After 48 and 72 hrs incubation, cytotoxicity was measured using thymidine incorporation as a marker. In addition to treatment with Y-90 labeled T101, control studies included Y-90 DTPA, Y-90 96.5 (non-specific MoAb), and excess unlabeled T101 prior to Y-90 T101. Selective cytotoxicity was observed with the Y-90 T101. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. TOHO UNIV,SCH MED,DEPT INTERNAL MED 1,OMORI NISHI,JAPAN. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RI Carrasquillo, Jorge/E-7120-2010 NR 27 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD SUM PY 1995 VL 8 IS 2 BP 81 EP 92 PG 12 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA RL327 UT WOS:A1995RL32700001 ER PT J AU CUNDY, KC PETTY, BG FLAHERTY, J FISHER, PE POLIS, MA WACHSMAN, M LIETMAN, PS LALEZARI, JP HITCHCOCK, MJM JAFFE, HS AF CUNDY, KC PETTY, BG FLAHERTY, J FISHER, PE POLIS, MA WACHSMAN, M LIETMAN, PS LALEZARI, JP HITCHCOCK, MJM JAFFE, HS TI CLINICAL PHARMACOKINETICS OF CIDOFOVIR IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB The pharmacokinetics of cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy) propyl] cytosine) were examined at five dose levels in three phase Im studies in a total of 42 human immunodeficiency virus-infected patients (with or without asymptomatic cytomegalovirus infection). Levels of cidofovir in serum following intravenous infusion were dose proportional over the dose range of 1.0 to 10.0 mg/kg of body weight and declined biexponentially with an overall mean +/- standard deviation terminal half-life of 2.6 +/- 1.2 h (n = 25). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 24 h. The overall mean +/- standard deviation total clearance of the drug from serum (148 +/- 25 ml/h/kg; n = 25) approximated renal clearance (129 +/- 42 ml/h/kg; n = 25), which was significantly higher (P < 0.001) than the baseline creatinine clearance in the same patients (83 +/- 21 ml/h/kg; n = 12). These data indicate that active tubular secretion played a significant role in the clearance of cidofovir. The steady-state volume of distribution of cidofovir was approximately 500 ml/kg, suggesting that the drug was distributed in total body water. Repeated dosing with cidofovir at 3.0 and 10.0 mg/kg/week did not alter the pharmacokinetics of the drug. Concomitant administration of intravenous cidofovir and oral probenecid to hydrated patients had no significant effect on the pharmacokinetics of cidofovir at a 3.0-mg/kg dose. At higher cidofovir doses, probenecid appeared to block tubular secretion of cidofovir and reduce its renal clearance to a level approaching glomerular filtration. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,SAN FRANCISCO,CA 94115. NIAID,BETHESDA,MD 20892. RP CUNDY, KC (reprint author), GILEAD SCI INC,353 LAKESIDE DR,FOSTER CITY,CA 94404, USA. OI Hitchcock, Michael/0000-0002-0631-3767; Polis, Michael/0000-0002-9151-2268 NR 11 TC 129 Z9 131 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1995 VL 39 IS 6 BP 1247 EP 1252 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RB370 UT WOS:A1995RB37000005 PM 7574510 ER PT J AU HAWKINS, ME MITSUYA, H MCCULLY, CM GODWIN, KS MURAKAMI, K POPLACK, DG BALIS, FM AF HAWKINS, ME MITSUYA, H MCCULLY, CM GODWIN, KS MURAKAMI, K POPLACK, DG BALIS, FM TI PHARMACOKINETICS OF DIDEOXYPURINE NUCLEOSIDE ANALOGS IN PLASMA AND CEREBROSPINAL-FLUID OF RHESUS-MONKEYS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; CONTINUOUS INFUSION; HIV INFECTION; 2',3'-DIDEOXYINOSINE; CHILDREN; ZIDOVUDINE; INVITRO; AIDS; PHARMACOLOGY; THERAPY AB The pharmacokinetics of 2',3'-dideoxyadenosine (ddA), didanosine, 2',3'-dideoxyguanosine (ddG), and 6-halogenated prodrugs of ddG, 6-chloro-ddG and 6-iodo-ddG, in plasma and cerebrospinal fluid (CSF) were studied in a non-human primate model, ddA was rapidly and completely deaminated to didanosine, such that didanosine concentration profiles in plasma and CSF were identical following administration of ddA and didanosine, The mean clearance of didanosine was 0.50 liters/h/kg, the terminal half-life was 1.8 h, and the CSF-to-plasma ratio was 4.8%, The disposition of ddG was similar, with a clearance of 0.70 liters/h/kg and a half-life of 1.7 h, The adenosine deaminase-mediated conversion of the 6-halogenated-ddG prodrugs to ddG was rapid but incomplete (48% for 6-chloro-ddG and 29% for 6-iodo-ddG), The CSF-to-plasma ratios of ddG with equimolar doses of ddG, 6-chloro-ddG, and 6-iodo-ddG were 8.5, 24, and 17%, respectively, but the actual ddG exposures in CSF (area under the CSF concentration-time curve) were comparable for ddG (12.1 mu M . h) and the 6-halogenated-ddG prodrugs (18.8 mu M . h for 6 chloro-ddG, 9.3 mu M . h for 6-iodo-ddG), 6-Chloro-ddG was not detectable in plasma or CSF, and the CSF-to-plasma ratio of 6-iodo-ddG was 9.4%, so the higher CSF-to-plasma ratios of ddG,vith the administration of the 6-halogenated-ddG prodrugs does not appear to be the result of enhanced penetration of the prodrug and subsequent dehalogenation to ddG, The penetration of ddG into CSF exceeds that of didanosine and is enhanced by administration of the 6-halogenated prodrugs, although the mechanism of this enhanced penetration is unclear. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NIPPON PAPER IND CORP,IWAKUNI RES LAB TECHNOL,IWAKUNI,YAMAGUCHI,JAPAN. NR 23 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1995 VL 39 IS 6 BP 1259 EP 1264 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RB370 UT WOS:A1995RB37000007 PM 7574512 ER PT J AU WALSH, TJ PETER, J MCGOUGH, DA FOTHERGILL, AW RINALDI, MG PIZZO, PA AF WALSH, TJ PETER, J MCGOUGH, DA FOTHERGILL, AW RINALDI, MG PIZZO, PA TI ACTIVITIES OF AMPHOTERICIN-B AND ANTIFUNGAL AZOLES ALONE AND IN COMBINATION AGAINST PSEUDALLESCHERIA-BOYDII SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID CENTRAL NERVOUS-SYSTEM; PETRIELLIDIUM-BOYDII; BRAIN-ABSCESS; TRANSPLANT RECIPIENT; FUNGAL-INFECTIONS; ENDOCARDITIS; KETOCONAZOLE; KERATITIS AB In order to develop new approaches to treatment of infections due to Pseudallescheria boydii, the in vitro antifungal activity of amphotericin B alone and in combination with miconazole, itraconazole, and fluconazole was studied. Combinations of amphotericin B and antifungal azoles were synergistic, additive, or indifferent in their interaction against P. boydii. Antagonism was not observed. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP WALSH, TJ (reprint author), NCI,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 28 TC 94 Z9 96 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1995 VL 39 IS 6 BP 1361 EP 1364 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RB370 UT WOS:A1995RB37000026 PM 7574531 ER PT J AU YANOVSKI, SZ AF YANOVSKI, SZ TI THE CHICKEN OR THE EGG - BINGE-EATING DISORDER AND DIETARY RESTRAINT SO APPETITE LA English DT Letter RP YANOVSKI, SZ (reprint author), NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892, USA. NR 1 TC 12 Z9 14 U1 1 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-6663 J9 APPETITE JI Appetite PD JUN PY 1995 VL 24 IS 3 BP 258 EP 258 DI 10.1016/S0195-6663(95)99811-X PG 1 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA RC946 UT WOS:A1995RC94600006 PM 7574573 ER PT J AU WINK, DA COOK, JA KRISHNA, MC HANBAUER, I DEGRAFF, W GAMSON, J MITCHELL, JB AF WINK, DA COOK, JA KRISHNA, MC HANBAUER, I DEGRAFF, W GAMSON, J MITCHELL, JB TI NITRIC-OXIDE PROTECTS AGAINST ALKYL PEROXIDE-MEDIATED CYTOTOXICITY - FURTHER INSIGHTS INTO THE ROLE NITRIC-OXIDE PLAYS IN OXIDATIVE STRESS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE OXIDATIVE STRESS; NITRIC OXIDE; LIPID PEROXIDATION; PROTECTION; ANTIOXIDANT ID LOW-DENSITY-LIPOPROTEIN; NITROGEN-DIOXIDE; ISCHEMIA-REPERFUSION; MYOCARDIAL-ISCHEMIA; PEROXYNITRITE; SUPEROXIDE; INHIBITION; RELEASE; CELLS; HYDROPEROXIDES AB Endogenously formed nitric oxide (NO) possesses diverse properties such as regulating physiological functions, exerting specific toxic effects, and protecting against various toxic substances. Recent studies suggest that in the presence of reactive oxygen species, NO can serve as an antioxidant. We show here that NO delivered from the NO donor compound, PAPA/NO (NH2(C3H6) (N[N(O)NO](C3H7)), protects Chinese hamster V79 lung fibroblasts from the cytotoxicity of t-butyl hydroperoxide and cumene hydroperoxide. In contrast, the other end products of PAPA/NO degradation in aqueous solution, NH2(C3H6)NH(C3H7) and nitrite, did not protect. The NONOate DEA/NO releases NO six times faster than PAPA/NO, yet did not afford protection, which implies that NO must be present throughout the alkyl hydroperoxide exposure. Measurements of NO concentrations released from PAPA/NO suggest that micromolar levels protect against cytotoxicity induced by alkyl hydroperoxides. These findings demonstrate that the flux of NO sustained over the duration of the peroxide exposure determines protection and not the total of NO delivered. These results suggest that concentrations of NO produced in the microenvironment of endothelial cells are high enough to protect cells from Fenton-type-mediated toxicity and support the premise that NO may exert a salutary effect in certain diseases associated with membrane damage. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,BETHESDA,MD 20892. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 42 TC 106 Z9 108 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1995 VL 319 IS 2 BP 402 EP 407 DI 10.1006/abbi.1995.1310 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RC221 UT WOS:A1995RC22100009 PM 7786021 ER PT J AU JIANG, JJ LIU, KJ SHI, XL SWARTZ, HM AF JIANG, JJ LIU, KJ SHI, XL SWARTZ, HM TI DETECTION OF SHORT-LIVED FREE-RADICALS BY LOW-FREQUENCY ELECTRON-PARAMAGNETIC-RESONANCE SPIN-TRAPPING IN WHOLE LIVING ANIMALS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE EPR; L-BAND; IN VIVO SULFITE FREE RADICAL; SPIN TRAPPING ID SULFUR-DIOXIDE; IN-VIVO; SULFITE; INVIVO; OXIDATION; ANION; SUPEROXIDE; ADDUCTS; OH AB We report the direct observation of sulfur trioxide anion free radical (SO3.-) from the body of live mice by using a low-frequency (1.2 GHz, L-band) EPR spin trapping method. Intraperitoneal injection of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (15 mmol/kg) used as trapping agent was followed by sequential iv injections of sodium sulfite (2-5 mmol/kg) and sodium dichromate (0.3 mmol/kg). The mouse was placed in an L-band loop gap resonator. The observed spectra consisted of two superposed components: DMPO/SO3.- (a(N) = 14.0, a(H) = 16.0) and Cr(V) (g = 1.9798). The time course for the generation and reduction of DMPO/SO3.- was followed. The signal intensity reached a maximum at about 7 min. lit vitro experiments carried out at 9.15 GHz confirmed the production of SO3.- under the conditions used for in vivo studies; the hyperfine splittings of DMPO/SO3.- produced in the in vitro experiments were the same as those produced in the in vivo studies, The production of SO3.- is supported by oxygen uptake studies, which show that the prior addition of 300 mM DMPO inhibits oxygen consumption by SO3.-. (C) 1995 Academic Press, Inc. C1 NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT RADIOL,HANOVER,NH 03755. RI Shi, Xianglin/B-8588-2012 NR 27 TC 28 Z9 30 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1995 VL 319 IS 2 BP 570 EP 573 DI 10.1006/abbi.1995.1332 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RC221 UT WOS:A1995RC22100031 PM 7786043 ER PT J AU YOUNG, ME RINTALA, DH ROSSI, CD HART, KA FUHRER, MJ AF YOUNG, ME RINTALA, DH ROSSI, CD HART, KA FUHRER, MJ TI ALCOHOL AND MARIJUANA USE IN A COMMUNITY-BASED SAMPLE OF PERSONS WITH SPINAL-CORD INJURY SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID SCREENING-TEST; LIFE SATISFACTION; SOCIAL SUPPORT; SUBSTANCE USE; MICHIGAN; DISABILITY; VETERANS; HANDICAP; ABUSE; DRUG AB The prevalence of self-reported alcohol and marijuana use, along with alcohol abuse as measured by the Short Michigan Alcoholism Screening Test, was assessed for a community-based sample (n = 123) of persons with spinal cord injury (SCI), Correlates of alcohol and marijuana use and alcohol abuse also were examined, including demographic variables, measures of impairment, disability, and handicap, SCI medical complications, and measures of subjective assessment such as health rating, health maintenance behaviors, depression, life satisfaction, perceived stress, pain, and social support, Prevalence of alcohol use (59%) and marijuana use (16%) in persons with SCI was less than that of comparison groups in the general population, However, prevalence of alcohol abuse (21%) exceeded that of general population studies. Participants who abused alcohol shared the following criteria: (1) perceived their overall health as worse than those who did not abuse alcohol; (2) were more depressed; and (3) experienced more stress in their lives than those who did not abuse alcohol, Participants who used marijuana were younger at the time of the study and were younger at injury, They were also more depressed and more stressed, The indications of alcohol abuse in one in five persons with SCI living in the community mandates that screening, treatment, and referrals be part of any rehabilitation treatment program. C1 BAYLOR COLL MED,DEPT PHYS MED & REHABIL,HOUSTON,TX 77030. NICHHD,NATL CTR MED REHABIL RES,WASHINGTON,DC. RP YOUNG, ME (reprint author), INST REHABIL & RES,4007 BELLAIRE BLVD,SUITE EE,HOUSTON,TX 77025, USA. NR 36 TC 33 Z9 35 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 1995 VL 76 IS 6 BP 525 EP 532 DI 10.1016/S0003-9993(95)80506-0 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA RB109 UT WOS:A1995RB10900006 PM 7763151 ER PT J AU CHAMBERS, T WHALEN, G KEHRL, JH KATZ, P AF CHAMBERS, T WHALEN, G KEHRL, JH KATZ, P TI GERMINAL CENTER B-LYMPHOCYTES POSSESS A UNIQUE PROTEIN-KINASE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20007. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R29 EP R29 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800108 ER PT J AU MAGID, M SAMMARITANO, LR KAPLAN, C PETERSON, M LOCKSHIN, MD AF MAGID, M SAMMARITANO, LR KAPLAN, C PETERSON, M LOCKSHIN, MD TI PLACENTAL PATHOLOGY IN SYSTEMIC LUPUS-ERYTHEMATOSUS - A PROSPECTIVE-STUDY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 SUNY STONY BROOK,STONY BROOK,NY 11794. HOSP SPECIAL SURG,CORNELL MED CTR,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R34 EP R34 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800115 ER PT J AU PANDO, JA DURAY, P YARBORO, C GOURLEY, MF GLUCK, V KLIPPEL, JH SCHUMACHER, HR AF PANDO, JA DURAY, P YARBORO, C GOURLEY, MF GLUCK, V KLIPPEL, JH SCHUMACHER, HR TI SYNOVIAL HISTOPATHOLOGY IN CLINICALLY NORMAL AND ASYMPTOMATIC JOINTS IN PATIENTS WITH EARLY ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. PENN STATE UNIV,PHILADELPHIA,PA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R20 EP R20 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800061 ER PT J AU HORWITZ, B AF HORWITZ, B TI REGIONS, NETWORKS - INTERPRETING FUNCTIONAL NEUROIMAGING DATA SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article AB The subtraction and covariance paradigms are two analytic techniques used with functional neuroimaging data. The first assumes that a brain region participating in a task should show altered neural activity (relative to a control task). The second assumes that tasks are mediated by networks of interacting regions. Images of mind attempts to link results from the subtraction paradigm with a network interpretation that could have been more explicitly done using the covariance paradigm. RP HORWITZ, B (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C 414,BETHESDA,MD 20892, USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1995 VL 18 IS 2 BP 360 EP 360 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA RP353 UT WOS:A1995RP35300066 ER PT J AU ROBINSON, DL AF ROBINSON, DL TI THE MEANING OF BASE-LINES SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article DE RUNNING HEAD; BASE-LINE CONDITIONS AB Images of mind superbly summarizes work on cognitive neuroscience using PET scanning. Some of the data emphasized suggests that parietal cortex is involved in the disengagement of attention. We have discovered neurons in awake monkeys which could perform this function. Another point of emphasis is the concept of neutral cues. Although an appealing concept, it is extremely difficult to define what is actually neutral. RP ROBINSON, DL (reprint author), NEI,SENSORIMOTOR RES LAB,VISUAL BEHAV SECT,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1995 VL 18 IS 2 BP 370 EP 370 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA RP353 UT WOS:A1995RP35300076 ER PT J AU SOBEL, BFX WETHERINGTON, CL RILEY, AL AF SOBEL, BFX WETHERINGTON, CL RILEY, AL TI THE CONTRIBUTION OF WITHIN-SESSION AVERAGING OF DRUG-APPROPRIATE AND VEHICLE-APPROPRIATE RESPONDING TO THE GRADED DOSE-RESPONSE FUNCTION IN DRUG DISCRIMINATION-LEARNING SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE DIAZEPAM; DISCRIMINATIVE STIMULUS; DRUG DISCRIMINATION; GRADED VS QUANTAL; NALOXONE; PENTOBARBITAL; RAT; TASTE AVERSIONS ID CONDITIONED TASTE-AVERSION; STIMULUS-CONTROL; REINFORCEMENT; MORPHINE; RATS AB Prior work within the taste aversion baseline of drug discrimination learning has demonstrated that the generalization function for individual rats is graded in nature. In such work, intermediate doses of the training drug produced intermediate levels of drug-appropriate responding. Under some conditions, such graded responding has been reported to be due to an averaging of quantal drug- and vehicle-appropriate responding at different periods within the session. The present experiment assessed the contribution of such averaging to the graded responding within the aversion design. Rats were first trained to discriminate either 1 mg/kg naloxone or 10 mg/kg pentobarbital from distilled water. They were then administered various doses of the training drug (or a different drug), and the within-session pattern of licking was monitored minute by minute over the 20 min session. Responding within the session was primarily either drug- or vehicle-appropriate. The specific pattern of drug- or vehicle-appropriate responding was presumably dependent upon the onset and/or offset of the drug stimulus. Thus, for the aversion baseline the graded response function for individual rats appears to be a function of the within-session averaging of quantal (either drug- or vehicle-appropriate) responding. C1 NIDA,BEHAV SCI RES BRANCH,ROCKVILLE,MD 20857. RP SOBEL, BFX (reprint author), AMERICAN UNIV,DEPT PSYCHOL,PSYCHOPHARMACOL LAB,WASHINGTON,DC 20016, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 1995 VL 6 IS 4 BP 348 EP 358 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RG577 UT WOS:A1995RG57700005 ER PT J AU ANDERSSON, HC KOHN, AD GAHL, WA KOHN, LD AF ANDERSSON, HC KOHN, AD GAHL, WA KOHN, LD TI PHOTOAFFINITY-LABELING OF LYSOSOMAL MEMBRANE-PROTEINS WITH [I-125]DIIODOTYROSINE, A SYSTEM-H LIGAND SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Note ID RAT-THYROID CELLS; TRANSPORT; MONOIODOTYROSINE; TYROSINE AB Percoll-purified rat thyroid FRTL-5 cell lysosomes were photoaffinity-labeled with [I-125]diiodotyrosine to identify proteins which bind diiodotyrosine, a ligand for lysosomal transport system h. SDS-PAGE and autoradiography of these membranes showed specific labeling of a 70-kDa protein and weak labeling of three smaller proteins. [I-125]Diiodotyrosine photolabeling of the 70-kDa protein was specifically competed against by ligands of lysosomal transport system h ligands. The 70-kDa protein was photolabeled more strongly in lysosomal membranes isolated from thyrotropin-stimulated cells when compared with those grown in the absence of thyrotropin, consistent with previous demonstrations that thyrotropin stimulates system h transport. The 70-kDa protein may represent some portion of the system h carrier protein. (C) 1995 Academic Press, Inc. C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD JUN PY 1995 VL 55 IS 1 BP 71 EP 73 DI 10.1006/bmme.1995.1034 PG 3 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA RF102 UT WOS:A1995RF10200011 PM 7551829 ER PT J AU WATANABE, H GAO, L SUGIYAMA, S DOEGE, K KIMATA, K YAMADA, Y AF WATANABE, H GAO, L SUGIYAMA, S DOEGE, K KIMATA, K YAMADA, Y TI MOUSE AGGRECAN, A LARGE CARTILAGE PROTEOGLYCAN - PROTEIN-SEQUENCE, GENE STRUCTURE AND PROMOTER SEQUENCE SO BIOCHEMICAL JOURNAL LA English DT Article ID CHONDROITIN SULFATE PROTEOGLYCAN; CORE PROTEIN; INTERGLOBULAR DOMAIN; NUCLEOTIDE-SEQUENCE; KERATAN SULFATE; CLONING; FORMS; ACID; RAT; IDENTIFICATION AB Seven genomic clones for mouse aggrecan core protein have been isolated including 3 kb of 5'- and 7 kb of 3'-flanking sequences. All exon sequences and their intron boundary sequences in these clones were identified and mapped by DNA sequencing. The gene spans at least 61 kb and contains 18 exons, Exon 1 encodes 5'-untranslated sequence and exon 2 contains a translation start codon, methionine. The coding sequence is 6545 bp for a 2132-amino-acid protein with calculated M(r) = 259131 including an 18-amino-acid signal peptide. There is a strong correlation between structural domains and exons. Notably, the chondroitin sulphate domain consisting of 1161 amino acids is encoded by a single exon of 3.6 kb. Although link protein has similar structural domains and subdomains, the sequence identity and the organization of exons encoding the subdomains B and B' of G1 and G2 domains revealed a strong similarity of mouse aggrecan to both human versican and rat neurocan, Primer extension analysis identified four transcription start sites which are close together. The promoter sequence showed high G/C content (65%) and contained several consensus binding motifs for transcription factors including Sp-1 and the glucocorticoid receptor. There are stretches of sequences similar to the promoter region of both the type-II collagen and link protein genes. These sequences may be important for cartilage gene expression. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOLEC BIOL,PORTLAND,OR 97201. AICHI MED UNIV,INST MOLEC SCI MED,NAGAKUTE,AICHI 48011,JAPAN. NR 37 TC 47 Z9 48 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1995 VL 308 BP 433 EP 440 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB325 UT WOS:A1995RB32500010 PM 7772024 ER PT J AU KUZNICKI, J WANG, TCL MARTIN, BM WINSKY, L JACOBOWITZ, DM AF KUZNICKI, J WANG, TCL MARTIN, BM WINSKY, L JACOBOWITZ, DM TI LOCALIZATION OF CA2+-DEPENDENT CONFORMATIONAL-CHANGES OF CALRETININ BY LIMITED TRYPTIC PROTEOLYSIS SO BIOCHEMICAL JOURNAL LA English DT Article ID CALCIUM-BINDING PROTEIN; IMMUNOHISTOCHEMICAL LOCALIZATION; INSITU HYBRIDIZATION; RAT; BRAIN; EXPRESSION; CALMODULIN; SEQUENCE; NEURONS; CELLS AB Calretinin is an EF-hand Ca2+-binding protein expressed predominantly in some neurons. We have found that the tryptic digestion pattern of rat recombinant calretinin depends on Ca2+ concentration as determined by SDS/PAGE, amino-acid-sequence analysis and electrospray-ionization MS. Ca2+-saturated calretinin was cleaved between amino acids 60 and 61 to yield two fragments, which accumulated during cleavage. Small amounts of the larger fragment (amino acid residues 61-271) were further cleaved from the C-terminal end. Ca2+-free calretinin was also cleaved between residues 60 and 61; however, under the latter conditions the fragment 61-271 was further cleaved from the N-terninal end. Native rat calretinin was cleaved by trypsin in a similar Ca2+-dependent fashion. All identified fragments of recombinant calretinin bound Ca-45(2+) on nitrocellulose filters, although to a different extent. The 61-271 fragment was released by EGTA from an octyl-agarose column in a manner similar to intact calretinin, while fragment 61-233 was not eluted by EGTA. These observations show that there are trypsin cleavage sites in calretinin that are available regardless of Ca2+ binding, other sites that are completely protected against trypsin on Ca2+-binding and sites which become partially available on Ca2+-binding. Together these data show that calretinin changes its conformation on Ca2+ binding and identify the regions which are exposed in apo and Ca2+-bound form. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP KUZNICKI, J (reprint author), NIMH,CLIN SCI LAB,BETHESDA,MD 20892, USA. NR 36 TC 28 Z9 28 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1995 VL 308 BP 607 EP 612 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB325 UT WOS:A1995RB32500035 PM 7772048 ER PT J AU Mao, Y Zang, LY Shi, XL AF Mao, Y Zang, LY Shi, XL TI Generation of free radicals by Cr(IV) from lipid hydroperoxides and its inhibition by chelators SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID CARCINOGEN CHROMATE; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; CHROMIUM(V); GLUTATHIONE; REDUCTION; ESR; PHENANTHROLINE; MECHANISM; COMPLEXES AB The generation of free radicals by Cr(IV) from lipid hydroperoxides was investigated by ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Reaction of Cr(VI) with ascorbate was used as a source of Cr(IV). Incubation of Cr(VI) with ascorbate generated Cr(IV) and Cr(V). Addition of cumene hydroperoxide generated DMPO/R(.) adduct with an enhancement of Cr(V) signal. Addition of Mn(II), whose function is to remove Cr(IV), caused dose-dependent inhibition of DMPO/R(.) formation. Similar results were obtained using t-butyl hydroperoxide. Metal ion chelators, deferoxamine, 1,10-phenanthroline and diethylenetriaminepentaacetic acid inhibited DMPO/R(.) formation in the order of deferoxamine > 1,10-phenanthroline > diethylenetriaminepentaacetic acid. The results suggest the possible role of Cr(IV) and its mediated free radical generation from lipid hydroperoxides in the mechanism of Cr(VI) carcinogenesis. C1 NCI,LAB EXPT PATHOL,NIH,BETHESDA,MD 20892. MONTANA STATE UNIV,DEPT CHEM,BOZEMAN,MT 59717. RI Shi, Xianglin/B-8588-2012 NR 38 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1995 VL 36 IS 2 BP 327 EP 337 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG016 UT WOS:A1995UG01600012 PM 7663436 ER PT J AU Ohama, T Jung, JE Park, SI Clouse, KA Lee, BJ Hatfield, D AF Ohama, T Jung, JE Park, SI Clouse, KA Lee, BJ Hatfield, D TI Identification of new selenocysteine tRNA([Ser]Sec) isoacceptors in human cell lines SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID TRANSFER-RNA; TRANSFER RNASEC; MAMMALIAN-CELLS; XENOPUS OOCYTES; UGA; ANTICODON AB The selenocysteine tRNA population was examined in a human T-cell line and in a human monocytic cell line for the occurrence of additional species of selenocysteine tRNA. At least three additional (and possibly more) selenocysteine isoacceptors were found which occur in minor levels as compared to the two major selenocysteine isoacceptors previously characterized. The possible significance of these newly observed species are discussed. C1 SEOUL NATL UNIV,INST MOLEC BIOL & GENET,MOLEC GENET LAB,SEOUL 151742,SOUTH KOREA. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Ohama, T (reprint author), NCI,NIH,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1995 VL 36 IS 2 BP 421 EP 427 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG016 UT WOS:A1995UG01600022 PM 7663446 ER PT J AU CLARK, DA FLANDERS, KC HIRTE, H DASCH, JR COKER, R MCANULTY, RJ LAURENT, GJ AF CLARK, DA FLANDERS, KC HIRTE, H DASCH, JR COKER, R MCANULTY, RJ LAURENT, GJ TI CHARACTERIZATION OF MURINE PREGNANCY DECIDUA TRANSFORMING GROWTH-FACTOR-BETA .1. TRANSFORMING GROWTH-FACTOR BETA-2-LIKE MOLECULES OF UNUSUAL MOLECULAR-SIZE RELEASED IN BIOACTIVE FORM SO BIOLOGY OF REPRODUCTION LA English DT Article ID VS-GRAFT REACTION; TGF-BETA; ACTIVE SUPPRESSION; CDNA SEQUENCE; MOUSE UTERUS; CELL-GROWTH; EXPRESSION; ANTIBODIES; ACTIVATION; SECRETION AB A novel type of bioactive transforming growth factor beta 2 (TGF beta 2)-related immunosuppressive activity, lower in molecular mass (20-23 kDa) than a conventional TGF beta 2 standard (25 kDa), has been shown to be released by non-T non-B suppressor cells of murine decidua into fetal bovine serum (FBS)-containing tissue culture medium during a 48-h incubation at 37 degrees C. Substitution of a serum-free medium has allowed direct PAGE-Western blotting and the demonstration in supernatant (prior to incubation at 37 degrees C) of a TGF beta 2-immunoreactive doublet at a higher molecular mass (26 and 27 kDa) than the standard but with apparent immunosuppressive activity. When decidua were incubated in serum-free medium at 37 degrees C, immunosuppressive activity in the supernatant increased to peak at 18 h in association with the appearance of the previously described lower molecular mass species of molecule. The doubler did not appear to be the result of glycosylation of a conventional 25-kDa TGF beta 2 and could be convened into the lower molecular mass form by incubation for 18 h at 37 degrees C, with pH 4.5 but not with pH 7.5 buffer; this incubation in the absence of decidual cells was not accompanied by increased immunosuppressive activity. This transformation could be blocked by a brief heating of the supernatant to 80 degrees C for 10 min to destroy enzymes present in supernatant prior to mixing with the acidic buffer, but biologic activity neutralizable by anti-TGF beta 2 was retained. These data suggest that TGF beta 2-like immunoregulatory activity in murine decidua is biologically active and that the size of the molecules may be modified by local enzymatic activity. The immunosuppressive factor was shown to be capable of stimulating procollagen production by confluent human fibroblasts assayed by HPLC measurement of hydroxyproline; but, in comparison to an authentic TGF beta 2 standard, the potency was much lower. On this basis, it would be possible to have local active immunosuppression without stimulation of fibrosis in implantation site decidua. C1 CELTRIX PHARMACEUT, SANTA CLARA, CA USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NATL HEART & LUNG INST, BIOCHEM UNIT, LONDON SW3, ENGLAND. RP MCMASTER UNIV, MOLEC VIROL IMMUNOL PROGRAM, RM 3V39, 1200 MAIN ST W, HAMILTON, ON L8N 3Z5, CANADA. RI McAnulty, Robin/C-2502-2008 OI McAnulty, Robin/0000-0003-1936-4245 NR 48 TC 36 Z9 39 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 1995 VL 52 IS 6 BP 1380 EP 1388 DI 10.1095/biolreprod52.6.1380 PG 9 WC Reproductive Biology SC Reproductive Biology GA QZ911 UT WOS:A1995QZ91100023 PM 7632846 ER PT J AU WEINBERG, CR WILCOX, AJ AF WEINBERG, CR WILCOX, AJ TI A MODEL FOR ESTIMATING THE POTENCY AND SURVIVAL OF HUMAN GAMETES IN-VIVO SO BIOMETRICS LA English DT Article DE EM ALGORITHM; FERTILITY; NATURAL FAMILY PLANNING; OVULATION; OVUM; SPERM ID TEMPERATURE; OVULATION; PREGNANCY; SPERM AB Sperm and ova are sensitive to numerous toxicants in animal studies; however, human vulnerability has been far more difficult to assess, due in part to a lack of methods for measuring the viable survival of human gametes in vivo. We present a parametric model for fertility, which assumes that the viable lifetime of the ovum is fixed while that of sperm is exponentially distributed. By reducing the number of parameters that must be estimated, compared to a previous approach, the model leads to improved tests for differences in sperm and egg survival between exposed and unexposed couples. Since it assumes that batches of sperm introduced on different days present independent competing ''risks'' (of fertilization) to the ovum, the model also provides for estimation of the age distribution, in days, of the sperm which actually fertilized the ova. This allows us to consider whether older sperm are more likely to produce defective embryos. We apply this model to data from a group of women who were intensively studied, beginning when they discontinued contraception in order to start a pregnancy. Participants kept daily records of intercourse. Daily urine specimens allowed the day of ovulation to be estimated and conceptions to be identified, based on assays of excreted hormones. Applying the parametric model to these data, the estimated mean viable lifetime for sperm is 1.4 days, while the lifetime of the ovum appears to be less than a day. The age distributions for the fertilizing sperm are remarkably similar for pregnancies ending in very early loss and pregnancies surviving long enough to be clinically recognized, suggesting that age of the fertilizing sperm is irrelevant to viability of the conceptus. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,A3-03,PO 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 12 TC 21 Z9 21 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1995 VL 51 IS 2 BP 405 EP 412 DI 10.2307/2532929 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RJ816 UT WOS:A1995RJ81600002 PM 7662833 ER PT J AU ZUCKER, DM ZERBE, GO WU, MC AF ZUCKER, DM ZERBE, GO WU, MC TI INFERENCE FOR THE ASSOCIATION BETWEEN COEFFICIENTS IN A MULTIVARIATE GROWTH CURVE MODEL SO BIOMETRICS LA English DT Article DE GROWTH CURVE ANALYSIS; LONGITUDINAL DATA ANALYSIS; MAXIMUM LIKELIHOOD; METHOD OF MOMENTS ID LINEAR-MODEL AB This paper generalizes the work of Blomqvist (1977, Journal of the American Statistical Association 72, 746-749) on inference for the relationship between the individual-specific slope and the individual-specific intercept in a linear growth curve model. The paper deals with longitudinal data involving one or more response variables and irregular follow-up times, with each response variable postulated to follow a linear growth curve model. The problem considered is inference concerning the association between one growth curve coefficient and another-for example, the slope and intercept for a selected response variable, or the two slopes for two different response variables-after adjusting for all remaining coefficients among all of the response variables. An inferential approach based on the method of moments and an inferential approach based on maximum likelihood are described, and the asymptotic properties of these procedures are presented. Extensions of the methodology to allow polynomial growth curves and baseline covariates are outlined. The methodology is illustrated with a practical example arising from a clinical trial in lung disease. C1 HEBREW UNIV JERUSALEM,DEPT STAT,IL-91905 JERUSALEM,ISRAEL. UNIV COLORADO,HLTH SCI CTR,DEPT PREVENT MED & BIOMETR,DENVER,CO 80262. RP ZUCKER, DM (reprint author), US NATL HEART LUNG & BLOOD INST,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 17 TC 22 Z9 22 U1 0 U2 4 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1995 VL 51 IS 2 BP 413 EP 424 DI 10.2307/2532930 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RJ816 UT WOS:A1995RJ81600003 PM 7662834 ER PT J AU ALBERT, PS MCSHANE, LM AF ALBERT, PS MCSHANE, LM TI A GENERALIZED ESTIMATING EQUATIONS APPROACH FOR SPATIALLY CORRELATED BINARY DATA - APPLICATIONS TO THE ANALYSIS OF NEUROIMAGING DATA SO BIOMETRICS LA English DT Article DE BINARY DATA; GENERALIZED ESTIMATING EQUATIONS; NEUROIMAGING DATA; SEMIVARIOGRAM ESTIMATES; SPATIAL CORRELATION ID LONGITUDINAL DATA-ANALYSIS; LINEAR-MODELS; REGRESSION; OUTCOMES AB This paper proposes a generalized estimating equations approach for the analysis of spatially correlated binary data when there are large numbers of spatially correlated observations on a moderate number of subjects. This approach is useful when the scientific focus is on modeling the marginal mean structure. Proper modeling of the spatial correlation structure is shown to provide large efficiency gains along with precise standard error estimates for inference on mean structure parameters. Generalized estimating equations for estimating the parameters of both the mean and spatial correlation structure are proposed. The use of semivariogram models for parameterizing the correlation structure is discussed, and estimation of the sample semivariogram is proposed as a technique for choosing parametric models and starting values for generalized estimating equations estimation. The methodology is illustrated with neuroimaging data collected as part of the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank. A simulation study demonstrates the importance of accurate modeling of the spatial correlation structure in data with large numbers of spatially correlated observations such as those found in neuroimaging studies. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. RP ALBERT, PS (reprint author), NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892, USA. NR 25 TC 80 Z9 80 U1 2 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1995 VL 51 IS 2 BP 627 EP 638 DI 10.2307/2532950 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RJ816 UT WOS:A1995RJ81600023 PM 7662850 ER PT J AU BERTRAM, R SMOLEN, P SHERMAN, A MEARS, D ATWATER, I MARTIN, F SORIA, B AF BERTRAM, R SMOLEN, P SHERMAN, A MEARS, D ATWATER, I MARTIN, F SORIA, B TI A ROLE FOR CALCIUM RELEASE-ACTIVATED CURRENT (CRAC) IN CHOLINERGIC MODULATION OF ELECTRICAL-ACTIVITY IN PANCREATIC BETA-CELLS SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRACELLULAR CA2+ STORES; B-CELLS; PLASMA-MEMBRANE; PHORBOL ESTER; ACINAR-CELLS; MOUSE ISLETS; K+ CHANNELS; GLUCOSE; OSCILLATIONS; DEPLETION AB S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. The ability of this single hypothesis, that CRAC is present in beta-cells, to explain so many phenomena motivates a more complete characterization of this current. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT BIOMED ENGN,BALTIMORE,MD 21205. UNIV ALICANTE,DEPT PHYSIOL,E-03080 ALACANT,SPAIN. UNIV ALICANTE,INST NEUROSCI,E-03080 ALACANT,SPAIN. RP BERTRAM, R (reprint author), NIDDKD,MATH RES BRANCH,BSA BLDG,SUITE 350,BETHESDA,MD 20892, USA. RI Martin, Franz/K-4197-2014 OI Martin, Franz/0000-0002-5745-8704 NR 46 TC 79 Z9 80 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1995 VL 68 IS 6 BP 2323 EP 2332 PG 10 WC Biophysics SC Biophysics GA RH660 UT WOS:A1995RH66000013 PM 7647236 ER PT J AU HOLTE, LL PETER, SA SINNWELL, TM GAWRISCH, K AF HOLTE, LL PETER, SA SINNWELL, TM GAWRISCH, K TI H-2 NUCLEAR-MAGNETIC-RESONANCE ORDER-PARAMETER PROFILES SUGGEST A CHANGE OF MOLECULAR SHAPE FOR PHOSPHATIDYLCHOLINES CONTAINING A POLYUNSATURATED ACYL-CHAIN SO BIOPHYSICAL JOURNAL LA English DT Article ID ORIENTATIONAL ORDER; NMR-SPECTROSCOPY; PHOSPHOLIPID BILAYER; LIPID-COMPOSITION; DYNAMIC STRUCTURE; MEMBRANES; RHODOPSIN; DISPERSIONS; CHOLESTEROL; ACID AB Solid-state H-2 nuclear magnetic resonance spectroscopy was used to determine the orientational order parameter profiles for a series of phosphatidylcholines with perdeuterated stearic acid, 18:0(d35), in position sn-1 and 18:1 omega 9, 18:2 omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3, or 22:6 omega 3 in position sn-2. The main phase transition temperatures were derived from a first moment analysis, and order parameter profiles of sn-1 chains were calculated from dePaked nuclear magnetic resonance powder patterns. Comparison of the profiles at 37 degrees C showed that unsaturation causes an inhomogenous disordering along the sn-1 chain. Increasing sn-2 chain unsaturation from one to six double bonds resulted in a 1.6kHz decrease in quadrupolar splittings of the sn-1 chain in the upper half of the chain (or plateau region) and maximum splitting difference of 4.4 kHz at methylene carbon 14. The change in chain order corresponds to a decrease in the 18:0 chain length of 0.4 +/- 0.2 Angstrom with 18:2 omega 6 versus 18:1 omega 9 in position sn-2. Fatty acids containing three or more double bonds in sn-2 showed a decrease in sn-1 chain length of 0.7 +/- 0.2 Angstrom compared with 18:1 omega 9. The chain length of all lipids decreased with increasing temperature. Highly unsaturated phosphatidylcholines (three or more double bonds in sn-2) had shorter sn-1 chains, but the chain length was somewhat less sensitive to temperature. The profiles reveal that the sn-1 chain exhibits a selective increase in motional freedom in a region located toward the bottom half of the chain as sn-2 unsaturation is increased. This corresponds to an area increase around carbon atom number 14 that is three to four times greater than the increase for the top part of the chain. A similar asymmetric decrease in order, largest toward the methyl end of the chain, was observed when 1-palmitoyl-2-oleoyl phosphatidylethanolamine goes from a lamellar to an inverse hexagonal (H-II) phase. This is consistent with a change to a more wedge-shaped space available for the acyl chain. C1 NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,NMR STUDIES SECT,BETHESDA,MD 20892. NR 49 TC 129 Z9 130 U1 0 U2 10 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1995 VL 68 IS 6 BP 2396 EP 2403 PG 8 WC Biophysics SC Biophysics GA RH660 UT WOS:A1995RH66000021 PM 7647244 ER PT J AU KRAFT, T CHALOVICH, JM YU, LC BRENNER, B AF KRAFT, T CHALOVICH, JM YU, LC BRENNER, B TI PARALLEL INHIBITION OF ACTIVE FORCE AND RELAXED FIBER STIFFNESS BY CALDESMON FRAGMENTS AT PHYSIOLOGICAL IONIC-STRENGTH AND TEMPERATURE CONDITIONS - ADDITIONAL EVIDENCE THAT WEAK CROSS-BRIDGE BINDING TO ACTIN IS AN ESSENTIAL INTERMEDIATE FOR FORCE GENERATION SO BIOPHYSICAL JOURNAL LA English DT Article ID ACTOMYOSIN ATPASE ACTIVITY; RABBIT PSOAS FIBERS; SKELETAL-MUSCLE FIBERS; MYOSIN SUBFRAGMENT-1; F-ACTIN; ADENOSINE-TRIPHOSPHATASE; COOPERATIVE BINDING; REGULATED ACTIN; TROPONIN-TROPOMYOSIN; VERTEBRATE SKELETAL AB Previously we showed that stiffness of relaxed fibers and active force generated in single skinned fibers of rabbit psoas muscle are inhibited in parallel by actin-binding fragments of caldesmon, an actin-associated protein of smooth muscle, under conditions in which a large fraction of cross-bridges is weakly attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These results suggested that weak cross-bridge attachment to actin is essential for force generation. The present study provides evidence that this is also true for physiological ionic strength (170 mM) at temperatures up to 30 degrees C, suggesting that weak cross-bridge binding to actin is generally required for force generation. In addition, we show that the inhibition of active force is not a result of changes in cross-bridge cycling kinetics but apparently results from selective inhibition of weak cross-bridge binding to actin. Together with our previous biochemical, mechanical, and structural studies, these findings support the proposal that weak cross-bridge attachment to actin is an essential intermediate on the path to force generation and are consistent with the concept that isometric force mainly results from an increase in strain of the attached cross-bridge as a result of a structural change associated with the transition from a weakly bound to a strongly bound actomyosin complex. This mechanism is different from the processes responsible for quick tension recovery that were proposed by Huxley and Simmons (Proposed mechanism of force generation in striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of force generation. C1 UNIV ULM,DEPT GEN PHYSIOL,W-7900 ULM,GERMANY. E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858. NIH,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR40540] NR 74 TC 62 Z9 62 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 JUN PY 1995 VL 68 IS 6 BP 2404 EP 2418 PG 15 WC Biophysics SC Biophysics GA RH660 UT WOS:A1995RH66000022 PM 7647245 ER PT J AU DUNBAR, CE COTTLERFOX, M OSHAUGHNESSY, JA DOREN, S CARTER, C BERENSON, R BROWN, S MOEN, RC GREENBLATT, J STEWART, FM LEITMAN, SF WILSON, WH COWAN, K YOUNG, NS NIENHUIS, AW AF DUNBAR, CE COTTLERFOX, M OSHAUGHNESSY, JA DOREN, S CARTER, C BERENSON, R BROWN, S MOEN, RC GREENBLATT, J STEWART, FM LEITMAN, SF WILSON, WH COWAN, K YOUNG, NS NIENHUIS, AW TI RETROVIRALLY MARKED CD34-ENRICHED PERIPHERAL-BLOOD AND BONE-MARROW CELLS CONTRIBUTE TO LONG-TERM ENGRAFTMENT AFTER AUTOLOGOUS TRANSPLANTATION SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-TRANSFER; HUMAN ADENOSINE-DEAMINASE; NONHUMAN-PRIMATES; PROGENITOR CELLS; EXPRESSION; INFECTION; CULTURE; MICE; TRANSDUCTION AB We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells, Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure, All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells, The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft, The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages. C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT TRANSFUS MED, BETHESDA, MD 20892 USA. NCI, MED BRANCH, BETHESDA, MD 20892 USA. NCI, CANC TREATMENT & EVALUAT PROGRAM, BETHESDA, MD 20892 USA. CELLPRO INC, BOTHELL, WA USA. AMGEN CORP, THOUSAND OAKS, CA USA. GENET THERAPY INC, GAITHERSBURG, MD USA. UNIV MASSACHUSETTS, CTR CANC, WORCESTER, MA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. RP DUNBAR, CE (reprint author), NHLBI, HEMATOL BRANCH, BLDG 10, ROOM 7C103, BETHESDA, MD 20892 USA. NR 50 TC 419 Z9 422 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 JUN 1 PY 1995 VL 85 IS 11 BP 3048 EP 3057 PG 10 WC Hematology SC Hematology GA RA136 UT WOS:A1995RA13600006 PM 7538814 ER PT J AU ROSENFELD, SJ KIMBALL, J VINING, D YOUNG, NS AF ROSENFELD, SJ KIMBALL, J VINING, D YOUNG, NS TI INTENSIVE IMMUNOSUPPRESSION WITH ANTITHYMOCYTE GLOBULIN AND CYCLOSPORINE AS TREATMENT FOR SEVERE ACQUIRED APLASTIC-ANEMIA SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; SAA-WORKING-PARTY; PROSPECTIVE RANDOMIZED TRIAL; HIGH-DOSE METHYLPREDNISOLONE; ANTILYMPHOCYTE GLOBULIN; THERAPY; ANDROGENS AB Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise ineligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA, Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage, Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients), Actuarial survival was 86% at 1 year and 72% at 2 years, These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia. RP ROSENFELD, SJ (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 2C390,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 227 Z9 239 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 JUN 1 PY 1995 VL 85 IS 11 BP 3058 EP 3065 PG 8 WC Hematology SC Hematology GA RA136 UT WOS:A1995RA13600007 PM 7756640 ER PT J AU MACIEJEWSKI, J SELLERI, C ANDERSON, S YOUNG, NS AF MACIEJEWSKI, J SELLERI, C ANDERSON, S YOUNG, NS TI FAS ANTIGEN EXPRESSION ON CD34(+) HUMAN MARROW-CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE-MEDIATED HEMATOPOIETIC SUPPRESSION IN-VITRO SO BLOOD LA English DT Article ID HUMAN PERIPHERAL-BLOOD; SEVERE APLASTIC-ANEMIA; PROGENITOR CELLS; SURFACE-ANTIGEN; BONE-MARROW; MOLECULAR-CLONING; LPR MICE; APOPTOSIS; INVITRO; GENE AB Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocytes is regulated by interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), cytokines that also have inhibitory effects on hematopoiesis, We investigated Fas antigen expression on human marrow cells and the effects of Fas activation on hematopoiesis in vitro, Freshly isolated immature hematopoietic cells, as defined by the CD34 marker, did not express Fas antigen at levels detectable by fluorescent staining, CD34(+) cells, which include progenitors and stem cells, showed low levels of Fas expression in culture, even in the presence of growth factors, Stimulation by TNF alpha and IFN gamma markedly increased Fas antigen expression on CD34(+) cells, Anti-Fas antibody, which mimics the action of the putative ligand, enhanced IFN gamma- and TNF alpha-mediated suppression of colony formation by bone marrow (BM) in a dose-dependent manner. This effect did not require the presence of accessory cells, Colony formation from mature (CD34(+) CD38(+)) and immature (CD34(+) CD38(-)) progenitor cells and long-term culture initiating cells were susceptible to the inhibitory action of anti-fas antibody in the presence of IFN gamma and TNF alpha. Apoptosis assays performed on total BM cells and CD34(+) cells showed that anti-fas antibody induced programmed cell death of CD34(+) BM cells. Fas antigen may be expressed as part of the differentiation program of hematopoietic cells. Fas antigen and its ligand may play a role in the pathophysiology of marrow failure states and in the elimination of abnormal hematopoietic cells in the course of an immune response. (C) 1995 by The American Society of Hematology. RP MACIEJEWSKI, J (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 57 TC 382 Z9 403 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1995 VL 85 IS 11 BP 3183 EP 3190 PG 8 WC Hematology SC Hematology GA RA136 UT WOS:A1995RA13600022 PM 7538820 ER PT J AU BLIGHT, AR COHEN, TI SAITO, K HEYES, MP AF BLIGHT, AR COHEN, TI SAITO, K HEYES, MP TI QUINOLINIC ACID ACCUMULATION AND FUNCTIONAL DEFICITS FOLLOWING EXPERIMENTAL SPINAL-CORD INJURY SO BRAIN LA English DT Article DE SPINAL CORD TRAUMA; GUINEA PIG; MACROPHAGE; KYNURENINE PATHWAY; INFLAMMATION ID KYNURENINE PATHWAY METABOLISM; CEREBROSPINAL-FLUID; 3-HYDROXYANTHRANILIC ACID; NEUROACTIVE KYNURENINES; MORPHOMETRIC ANALYSIS; DELAYED INCREASES; IMMUNE ACTIVATION; CEREBRAL-ISCHEMIA; L-TRYPTOPHAN; RAT-BRAIN AB Quinolinic acid (QUIN) is an excitotoxic tryptophan metabolite that is produced by activated macrophages. Accumulations of QUIN are implicated in the aetiology of a broad spectrum of human neurological diseases, particularly inflammatory conditions. To determine whether and QUIN is an endogenous neurotoxin requires agents that reduce and QUIN synthesis, and animal models where QUIN levels increase in association with neurological disease. Compression injury of the spinal cord of guinea pigs results in secondary neurological deficits, related to inflammation and macrophage activation. We evaluated whether 4-chloro-3-hydroxyanthranilate (4Cl-3HAA), an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase reduces QUIN accumulations in this model and influences the progression of neurological deficits. Intraperitoneal injections of 4Cl-3HAA (100 mg/kg every 12 h) attenuated QUIN accumulations in spinal cord following injury, and reduced the severity of delayed functional deficits. Intraperitoneal injections of the macrophage toxin, silica, also reduced QUIN levels and attenuated neurological deficits. A direct subdural infusion of Cl-3HAA into the injured spinal cord (50 mu M, 1 mu l/h) promptly exacerbated functional impairments, which suggests that the infusate had direct toxic effects. These studies demonstrate that guinea pigs with spinal cord injury constitute a useful model to study the mechanisms that increase central nervous system (CNS) QUIN levels in conditions of CNS inflammation, and to evaluate the neurochemical and neurological effects of agents designed to reduce the accumulations of QUIN and other potential pathogenic mediators within the CNS. The results are consistent with a contributory role for QUIN in the pathogenesis of secondary functional impairments following spinal cord injury, although the possibility that 4Cl-3HAA had additional effects independent of QUIN cannot be excluded. Further studies are required to determine whether the beneficial effects of 4Cl-3HAA are sustained While it is unknown whether secondary inflammatory processes contribute significantly to neurological deficits in human spinal cord injury, strategies that reduce the accumulation of QUIN are worthy of consideration and evaluation as a therapeutic target. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. UNIV N CAROLINA,DIV NEUROSURG,CHAPEL HILL,NC 27599. FU NINDS NIH HHS [NS-21122] NR 81 TC 82 Z9 84 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1995 VL 118 BP 735 EP 752 DI 10.1093/brain/118.3.735 PN 3 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RH882 UT WOS:A1995RH88200011 PM 7600090 ER PT J AU APPOLLONIO, I CLARK, K KOSSLYN, S HALLETT, M GRAFMAN, J AF APPOLLONIO, I CLARK, K KOSSLYN, S HALLETT, M GRAFMAN, J TI SPATIAL PERCEPTION AND IMAGERY IN PARKINSON DISEASE SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 NINCDS,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1995 VL 28 IS 1 BP 108 EP 109 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA RF548 UT WOS:A1995RF54800082 ER PT J AU DRAKE, JC VOELLER, DM ALLEGRA, CJ JOHNSTON, PG AF DRAKE, JC VOELLER, DM ALLEGRA, CJ JOHNSTON, PG TI THE EFFECT OF DOSE AND INTERVAL BETWEEN 5-FLUOROURACIL AND LEUCOVORIN ON THE FORMATION OF THYMIDYLATE SYNTHASE TERNARY COMPLEX IN HUMAN CANCER-CELLS SO BRITISH JOURNAL OF CANCER LA English DT Article DE 5-FLUOROURACIL; LEUCOVORIN; THYMIDYLATE SYNTHASE TERNARY COMPLEX ID ADVANCED COLORECTAL-CARCINOMA; FOLINIC ACID; BIOCHEMICAL MODULATION; RANDOMIZED TRIAL; CYTO-TOXICITY; COLON-CANCER; FLUOROURACIL; BREAST; FLUOROPYRIMIDINES; ENHANCEMENT AB We examined the importance of dosing interval between leucovorin (LCV) and 5-fluorouracil (5-FU) on intracellular thymidylate synthase (TS) ternary complex, free TS and total TS protein levels in human MCF-7 breast and NCI H630 colon cancer cell lines. A 2- to 3-fold increase in total TS was noted when either cell line was exposed to 5-FU 10 mu M plus LCV (0.01-10 mu M) compared with a 1.4- to 1.6-fold increase in total TS due to 5-FU 10 mu M alone. The amount of TS ternary complex formed was 2- to 3-fold higher in both cell lines treated with the combination of 5-FU and LCV compared with 5-FU alone. TS complex formation and total TS protein increased with LCV dose (0.1-10 mu M). In MCF-7 cells, the maximal increase in total TS protein and TS ternary complex formation was observed when 5-FU was delayed for 4 h after the start of LCV exposure. In NCI H630 cells, maximal total TS protein and ternary complex formation occurred when 5-FU was delayed for 18 h after the start of LCV exposure. The amount of free TS did not change in either cell line whether 5-FU was given concurrently with LCV or delayed for up to 24 h. The accumulation rate of intracellular folates in the form of higher glutamates Glu(3)-Glu(5) was rapid in MCF-7 cells (maximal formation after 4 h), whereas in H630 cells accumulation of higher polyglutamates continued to increase up to 18 h. The time of peak folate polyglutamate (Glu(3)-Glu(5)) formation coincided with the lime of peak TS complex formation and total TS protein in each cell line. In these human carcinoma cell lines, the LCV dose and interval between 5-FU and LCV play a role in increased TS total protein and TS ternary complex; however, the amount of free TS is independent of the interval between 5-FU and LCV. The time-and dose-dependent increases in TS ternary complex and TS total protein are associated with differences in the accumulation of folate polyglutamates in these cell lines. C1 NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. NR 38 TC 18 Z9 19 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1995 VL 71 IS 6 BP 1145 EP 1150 DI 10.1038/bjc.1995.224 PG 6 WC Oncology SC Oncology GA RB646 UT WOS:A1995RB64600006 PM 7779703 ER PT J AU PESTALOZZI, BC MCGINN, CJ KINSELLA, TJ DRAKE, JC GLENNON, MC ALLEGRA, CJ JOHNSTON, PG AF PESTALOZZI, BC MCGINN, CJ KINSELLA, TJ DRAKE, JC GLENNON, MC ALLEGRA, CJ JOHNSTON, PG TI INCREASED THYMIDYLATE SYNTHASE PROTEIN-LEVELS ARE PRINCIPALLY ASSOCIATED WITH PROLIFERATION BUT NOT CELL-CYCLE PHASE IN ASYNCHRONOUS HUMAN CANCER-CELLS SO BRITISH JOURNAL OF CANCER LA English DT Article DE CELL CYCLE; TS ID MOUSE FIBROBLASTS; ANTIBODY KI-67; SYNTHETASE; 5-FLUOROURACIL; QUANTITATION; EXPRESSION; CARCINOMA; LINES; TUMOR AB We have analysed cell cycle variations in thymidylate synthase (TS) protein in asynchronously growing NCl H630 and HT 29 colon cancer and MCF-7 breast cancer cell lines. Western immunoblot analysis using the TS 106 monoclonal antibody revealed a 14- to 24-fold variation in TS levels between the peak exponential and confluent growth phase in the three cell lines. Similar variations in TS levels and TS activity were detected using the 5-fluorodeoxyuridine monophosphate and deoxyuridine monophosphate biochemical assays. The percentage of cells in S-phase, which paralleled changes in TS levels, reached a maximum of 38-60% in asynchronous exponentially growing cells compared with 5-10% in confluent cells. In asynchronous exponential cells, analysis of TS levels in each cell cycle phase using two-parameter flow cytometric analysis revealed that TS protein levels were 1.3- to 1.5-fold higher in S than in G(0)/G(1) phase cells, and 1.5- to 1.8-fold higher in G(2)/M than G(0)/G(1) cells. Similar differences of 1.1- to 1.5-fold between G(0)/G(1) and S-phase and 1.6- to 1.9-fold between G(0)/G(1) and G(2)/M-phase were detected by Western immunoblot and biochemical assays. TS protein was not detectable by Western blot analysis, flow cytometry or biochemical analysis in the G(0)/G(1) population of confluent cells. Twenty-six per cent of cells in this population were G(0) cells compared with 2% in exponentially growing cells. In contrast to TS, a 4-fold difference in thymidine kinase (TK) was detected between G(0)/G(1) and S-phase cells in exponentially growing MCF-7 cells. The level of TS enzyme is associated with cellular proliferation and the percentage of cells in S-phase; however, TS protein is not exclusively associated with S-phase in asynchronously growing cells. The variation in TS levels between exponentially growing and confluent cell population appears to be due to differences in TS levels between G(0) and G(1) cells. C1 NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53792. FU NCI NIH HHS [P0 1 CA 52686] NR 28 TC 66 Z9 66 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1995 VL 71 IS 6 BP 1151 EP 1157 DI 10.1038/bjc.1995.225 PG 7 WC Oncology SC Oncology GA RB646 UT WOS:A1995RB64600007 PM 7779704 ER PT J AU MIRZAYANS, R AUBIN, RA BOSNICH, W BLATTNER, WA PATERSON, MC AF MIRZAYANS, R AUBIN, RA BOSNICH, W BLATTNER, WA PATERSON, MC TI ABNORMAL PATTERN OF POST-GAMMA-RAY DNA-REPLICATION IN RADIORESISTANT FIBROBLAST STRAINS FROM AFFECTED MEMBERS OF A CANCER-PRONE FAMILY WITH LI-FRAUMENI SYNDROME SO BRITISH JOURNAL OF CANCER LA English DT Article DE POST-GAMMA-RAY DNA REPLICATION; RADIORESISTANT CELLS; LI-FRAUMENI SYNDROME; MUTATED P53 GENE; DNA REPLICONS ID ATAXIA-TELANGIECTASIA CELLS; IONIZING-RADIATION; SKIN FIBROBLASTS; P53 PROTEIN; BREAST-CANCER; X-IRRADIATION; GENE; CHECKPOINT; MUTATIONS; INVITRO AB Non-malignant dermal fibroblast strains, cultured from affected members of a Li-Fraumeni syndrome (LFS) family with diverse neoplasms associated with radiation exposure, display a unique increased resistance to the lethal effects of gamma-radiation. In the studies reported here, this radioresistance (RR) trait has been found to correlate strongly with an abnormal pattern of post-gamma-ray DNA replicative synthesis, as monitored by radiolabelled thymidine incorporation and S-phase cell autoradiography. In particular, the time interval between the gamma-ray-induced shutdown of DNA synthesis and its subsequent recovery was greater in all four RR strains examined and the post-recovery replication rate was much higher and was maintained longer than in normal and spousal controls. Alkaline sucrose sedimentation profiles of pulse-labelled cellular DNA indicated that the unusual pattern of DNA replication in irradiated RR strains may be ascribed to anomalies in both replicon initiation and DNA chain elongation processes. Moreover, the RR strain which had previously displayed the highest post-gamma-ray clonogenic survival was found to harbour a somatic (codon 234) mutation (presumably acquired during culture in vitro) in the same conserved region of the p53 tumour-suppressor gene as the germline (codon 245) mutation in the remaining three RR strains from other family members, thus coupling the RR phenotype and abnormal post-gamma-ray DNA synthesis pattern with faulty p53 expression. Significantly, these two aberrant radioresponse end points, along with documented anomalies in c-myc and c-raf-1 proto-oncogenes, are unprecedented among other LFS families carrying p53 germline mutations. We thus speculate that this peculiar cancer-prone family may possess in its germ line a second, as yet unidentified, genetic defect in addition to the p53 mutation. C1 UNIV ALBERTA,CROSS CANC INST,DEPT EXPTL ONCOL,MOLEC ONCOL PROGRAM,EDMONTON,AB T6G 1Z2,CANADA. UNIV ALBERTA,DEPT ONCOL,EDMONTON,AB T6G 1Z2,CANADA. DEPT HLTH & WELF,SIR FG BANTING RES CTR,LIFE SCI DIV BIOTECHNOL,OTTAWA,ON K1A 0L2,CANADA. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CP-21029] NR 54 TC 28 Z9 28 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1995 VL 71 IS 6 BP 1221 EP 1230 DI 10.1038/bjc.1995.237 PG 10 WC Oncology SC Oncology GA RB646 UT WOS:A1995RB64600019 PM 7779715 ER PT J AU DATILES, MB MAGNO, BV FREIDLIN, V AF DATILES, MB MAGNO, BV FREIDLIN, V TI STUDY OF NUCLEAR CATARACT PROGRESSION USING THE NATIONAL-EYE-INSTITUTE SCHEIMPFLUG SYSTEM SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GLARE SENSITIVITY; IMAGE-ANALYSIS; CLASSIFICATION; PHOTOGRAPHS; CONTRAST; CAMERA AB Aims-A study was conducted to determine the capability of the recently developed National Eye Institute (NEI) Scheimpflug cataract imaging system in detecting changes in the nuclear region of the lens over a 1 year period. Methods-Twenty five eyes with pure nuclear cataracts with mean nuclear densities less than or equal to 0.30 optical density units (ODU) as well as 30 normal control eyes were each examined at baseline and 12 months later. Computerised densitometry using the NEI Scheimpflug cataract imaging system was performed. Clinical grading of the lenses was also done using the Lens Opacities Classification System II (LOGS II). For densitometry, a change of plus or minus 0.023 ODU (the 99% range) in mean density in the nuclear area was considered a progression or regression at 1 year. Results-Using the Scheimpflug densitometry, 14 of the 25 cataractous eyes showed significant progression at 1 year. In the normal control group, only three of the 30 eyes showed significant progression. In contrast, using the LOGS II clinical grading, only two of the 25 cataractous eyes showed a one step increase, two of the 30 controls progressed at 1 year, and none regressed. There was no significant difference in visual acuity. Conclusion-This study suggests the value of the NEI Scheimpflug cataract imaging system in detecting nuclear change within 1 year. However, clinically significant changes may require longer follow up periods. These data will be useful in planning future longitudinal studies of nuclear cataracts, such as for clinical trials of anticataract drugs. C1 NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. RP DATILES, MB (reprint author), NEI,CATARACT & CORNEAL DIS SECT,OPHTHALM GENET & CLIN SERV BRANCH,10 CTR DR,MSC 1860,BLDG 10,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 30 TC 27 Z9 28 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 1995 VL 79 IS 6 BP 527 EP 534 DI 10.1136/bjo.79.6.527 PG 8 WC Ophthalmology SC Ophthalmology GA RB148 UT WOS:A1995RB14800006 PM 7626567 ER PT J AU LOPEZ, MLL FREIDLIN, V DATILES, MB AF LOPEZ, MLL FREIDLIN, V DATILES, MB TI LONGITUDINAL-STUDY OF POSTERIOR SUBCAPSULAR OPACITIES USING THE NATIONAL-EYE-INSTITUTE COMPUTER PLANIMETRY SYSTEM SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETROILLUMINATION PHOTOGRAPHS; CATARACTS AB Background-The National Eye Institute (NEI) computer planimetry system has proved to be helpful in cross sectional studies by providing clinically useful area measurements of posterior subcapsular cataracts (PSC) and other opacities from retroillumination photographs. In this study, we evaluated the worth of this system in detecting PSC area changes over time. Methods-Using the Neitz-Kawara camera, retroillumination photographs of the PSCs of 51 eyes were obtained every 6 months for an average of 25 months. The PSCs were outlined in a masked fashion on plastic overlays. Their tracings were then digitised on to a computer using a scanner. PSC area was determined using a special software program. For each eye, the rate of PSC area change was estimated by the slope of the regression line fitted to the follow up measurements. Cataract progression was classified as significant if the slope exceeded a critical value. Results-These showed that 14 of the 51 eyes had PSC progression, while 37 did not change. Conclusion-This study suggests the system is useful for longitudinally monitoring PSC area changes from retroillumination photographs. This system would serve in natural history studies of PSCs and in clinical trials of anticataract drugs. The slope based test can play a part in longitudinal studies with irregular time intervals and variable number of visits. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 15 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 1995 VL 79 IS 6 BP 535 EP 540 DI 10.1136/bjo.79.6.535 PG 6 WC Ophthalmology SC Ophthalmology GA RB148 UT WOS:A1995RB14800007 PM 7626568 ER PT J AU KULYNYCH, JJ VLADAR, K FANTIE, BD JONES, DW WEINBERGER, DR AF KULYNYCH, JJ VLADAR, K FANTIE, BD JONES, DW WEINBERGER, DR TI NORMAL ASYMMETRY OF THE PLANUM TEMPORALE IN PATIENTS WITH SCHIZOPHRENIA - 3-DIMENSIONAL CORTICAL MORPHOMETRY WITH MRI SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID MONOZYGOTIC TWINS DISCORDANT; MAGNETIC-RESONANCE; CEREBRAL ASYMMETRY; AFFECTIVE-DISORDER; HUMAN-BRAIN; COMPUTED-TOMOGRAPHY; LOBE; ABNORMALITIES; POSTMORTEM; AREA AB Background. Abnormal cerebral anatomical lateralisation has been reported in schizophrenia and may implicate anomalous neurodevelopment in the aetiology of this disease. A popular recent hypothesis has predicted that such disturbances in normal lateralisation should be especially apparent in the morphology of the temporal lobes. Method. A temporal cortical region lying in the plane of the Sylvian fissure - known as the planum temporale - exhibits pronounced leftward asymmetry in normal right-handed males. We compared lateralisation of the planum temporale in schizophrenic and control males using MRI surface-rendering morphometry of the supratemporal cortex. Results. Contrary to the lateralisation hypothesis, normal patterns of leftward planum asymmetry were detected in both the schizophrenic and control groups. Schizophrenics and controls also exhibited a predicted symmetry in the bilateral areas of Heschl's gyrus, a supratemporal cortical structure immediately anterior to the planum. Conclusion. These data do not support the notion that neurodevelopmental mechanisms of cerebral asymmetry are abnormal in schizophrenia. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. AMERICAN UNIV,HUMAN NEUOPSYCHOL LAB,WASHINGTON,DC 20016. NR 58 TC 72 Z9 72 U1 2 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 1995 VL 166 BP 742 EP 749 DI 10.1192/bjp.166.6.742 PG 8 WC Psychiatry SC Psychiatry GA RF270 UT WOS:A1995RF27000009 PM 7663822 ER PT J AU GOANS, RE WEISS, GH ABRAMS, SA PEREZ, MD YERGEY, AL AF GOANS, RE WEISS, GH ABRAMS, SA PEREZ, MD YERGEY, AL TI CALCIUM TRACER KINETICS SHOW DECREASED IRREVERSIBLE FLOW TO BONE IN GLUCOCORTICOID-TREATED PATIENTS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CALCIUM; KINETICS; STABLE ISOTOPE; GLUCOCORTICOIDS; OSTEOPENIA; MATHEMATICAL MODELING ID DERMATOMYOSITIS; POLYMYOSITIS AB Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of Ca-42 were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NIH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX 77030. OI Abrams, Steven/0000-0003-4972-9233 NR 13 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JUN PY 1995 VL 56 IS 6 BP 533 EP 535 DI 10.1007/BF00298584 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ590 UT WOS:A1995QZ59000007 PM 7648481 ER PT J AU BIESECKER, LG DERENZO, EG GRADY, C MACKAY, CR AF BIESECKER, LG DERENZO, EG GRADY, C MACKAY, CR TI GENETICS - FOREWORD SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Discussion C1 NIH,CTR CLIN,BETHESDA,MD 20892. RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD SUM PY 1995 VL 4 IS 3 BP 387 EP 400 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA RG429 UT WOS:A1995RG42900016 PM 7551153 ER PT J AU YU, KF AF YU, KF TI A NECESSARY AND SUFFICIENT CONDITION FOR THE STRONG CONSISTENCY OF A FAMILY OF ESTIMATORS OF THE COMMON ODDS RATIO SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE ODDS RATIO; SPARSE TABLES; STRONG CONSISTENCY; ASYMPTOTIC NORMALITY ID SPARSE; VARIANCE; TABLES; RISK AB A family of easily computable estimators of the odds ratio of a number of two-by-two contingency tables is proposed. It includes the well-known Mantel-Haenszel estimator as a special case. A necessary and sufficient condition is given for the strong consistency of the estimators for the case when the tables are sparse and the number of tables becomes large. The condition also ensures the asymptotic normality of this family of estimators. A family of consistent estimators is proposed for the variances of the asymptotic distributions. In the case of the Mantel-Haenszel estimator, the validity of Breslow's (1981, Biometrika) condition for the consistency and asymptotic normality is questioned. Examples are given to demonstrate that it is neither necessary nor sufficient for the consistency of the Mantel-Haenszel estimator. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NR 14 TC 1 Z9 1 U1 0 U2 0 PU CANADIAN JOURNAL STATISTICS PI OTTAWA ONTARIO PA 675 DENBURY AVENUE, OTTAWA ONTARIO K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD JUN PY 1995 VL 23 IS 2 BP 215 EP 225 DI 10.2307/3315446 PG 11 WC Statistics & Probability SC Mathematics GA RN854 UT WOS:A1995RN85400009 ER PT J AU RAZZOUK, BI HEIDEMAN, RL FRIEDMAN, HS JENKINS, JJ KUN, LE FAIRCLOUGH, DL HOROWITZ, ME AF RAZZOUK, BI HEIDEMAN, RL FRIEDMAN, HS JENKINS, JJ KUN, LE FAIRCLOUGH, DL HOROWITZ, ME TI A PHASE-II EVALUATION OF THIOTEPA FOLLOWED BY OTHER MULTIAGENT CHEMOTHERAPY REGIMENS IN INFANTS AND YOUNG CHILDREN WITH MALIGNANT BRAIN-TUMORS SO CANCER LA English DT Article DE THIOTEPA; INFANTS; BRAIN TUMORS; CLINICAL TRIAL; MEDULLOBLASTOMA ID POSTOPERATIVE CHEMOTHERAPY; IRRADIATION; SURVIVAL; AGE AB Background. Chemotherapy may be used to delay the need for cranial irradiation in infants and young children with malignant central nervous system (CNS) tumors. The polyfunctional alkylator thiotepa (TT) possesses significant in vitro and in vivo acticity in many central nervous system tumors. Before the introduction of a multiagent chemotherapy previously shown to be active in such tumors, thiotepa alone was evaluated in an upfront therapeutic window. Methods. Twenty young children with CNS tumors (19 newly diagnosed, 1 recurrent) were treated with two cycles of TT before response evaluation. Patients on thiotepa without disease progression went on to receive further chemotherapy consisting of alternatiing cycles of cyclophasphamide plus vincrisine, cisplatin plus etoposide, and further TT. Patients with disease progression received radiation therapy. Results. Low objective rates of response and poor survival led to early study termination. Of 17 patients evaluable for response, 6 (35%) demonstrated disease progression during initial TT therapy. 0nly two objective responses were noted, both in patients with medulloblastoma. Among the 19 patients evaluable for survival, the overall and progression free survivals were 45% and 20%, respectively, at 3 years postdiagnosis. Myelosuppression was the dominant treatment-related toxicity. Conclusions. Although the numbers of patients were small, thiotepa as used in this study was asociated with a poor objective response rate of disease progression. These results may be partly related to TT's significant myelosuppressive effects and the postponement of more effective chemotherapy. C1 ST JUDE CHILDRENS RES HOSP,DEPT HEMATOL ONCOL,MEMPHIS,TN 38101. ST JUDE CHILDRENS RES HOSP,DEPT PATHOL & LAB MED,MEMPHIS,TN 38101. ST JUDE CHILDRENS RES HOSP,DEPT RADIAT ONCOL,MEMPHIS,TN 38101. ST JUDE CHILDRENS RES HOSP,DEPT BIOSTAT & INFORMAT SERV,MEMPHIS,TN 38101. DUKE UNIV MED CTR,DEPT PEDIATR ONCOL,DURHAM,NC 27706. NCI,PEDIATR ONCOL BRANCH,BETHESDA,MD 20892. TEXAS CHILDRENS CANCER CTR,HOUSTON,TX. BAYLOR COLL MED,HEMATOL SERV,HOUSTON,TX. FU NCI NIH HHS [PA30 CA-21765] NR 13 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1995 VL 75 IS 11 BP 2762 EP 2767 DI 10.1002/1097-0142(19950601)75:11<2762::AID-CNCR2820751121>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA QY896 UT WOS:A1995QY89600033 PM 7743483 ER PT J AU DAWSEY, SM LEWIN, KJ AF DAWSEY, SM LEWIN, KJ TI ESOPHAGEAL MORPHOLOGY FROM LINXIAN, CHINA - SQUAMOUS HISTOLOGIC-FINDINGS IN 754 PATIENTS - REPLY SO CANCER LA English DT Letter ID HIGH-RISK POPULATIONS; PRECURSOR LESIONS; PRECANCEROUS LESIONS; CANCER; IRAN C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. RP DAWSEY, SM (reprint author), NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1995 VL 75 IS 11 BP 2780 EP 2781 PG 2 WC Oncology SC Oncology GA QY896 UT WOS:A1995QY89600022 ER PT J AU JamisDow, CA Klecker, RW Katki, AG Collins, JM AF JamisDow, CA Klecker, RW Katki, AG Collins, JM TI Metabolism of taxol by human and rat liver in vitro: A screen for drug interactions and interspecies differences SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE drug metabolism; species differences; drug interactions ID HYPERSENSITIVITY REACTIONS; HUMAN HEPATOCYTES; PHASE-II; KETOCONAZOLE; CYCLOSPORINE; TRIAL; AGENT AB Human liver slices, human liver microsomes, and rat liver microsomes were used to investigate the metabolism of H-3-taxol. The effects of drugs frequently coadministered with taxol and the effects of several cytochrome P450 system probes were studied. In all, 16 compounds were screened. After incubation with liver slices or with microsomal protein, H-3-taxol was converted into several radioactive species resolved by HPLC. There were qualitative and quantitative species differences in the metabolism of taxol. The pattern of metabolism was similar for both human-derived preparations, with 6 alpha-hydroxytaxol being the major metabolite peak. In drug interaction studies performed with human liver microsomes, cimetidine 80 mu M, and diphenhydramine 200 mu M, had little or no effect on 6 alpha-hydroxytaxol formation. Quinidine, ketoconazole, dexamethasone and Cremophor EL inhibited 6 alpha-hydroxytaxol formation with IC50 values of 36 mu M, 37 mu M, 16 mu M and 1 mu l/ml, respectively, but these concentrations exceed the usual clinical range. Cremophor EL also inhibited microsomal metabolism of taxol, but at 2 mu l/ml it had little or no effect on 6 alpha-hydroxytaxol production by human liver slices. These results suggest that: (1) taxol is metabolized by the cytochrome P450 system; (2) taxol metabolism is different in humans than in rats; (3) taxol metabolism in humans is unlikely to be altered by cimetidine, dexamethasone, or diphenhydramine, drugs regularly coadministered with taxol; (4) taxol metabolism can be indirectly affected by Cremophor EL, the formulation vehicle; (5) taxol metabolism may be altered by concentrations of ketoconazole achievable in humans only at very high doses; and (6) taxol metabolism and drug interaction studies of clinical relevance can be performed in vitro with human liver microsomes and human liver slices, but not with rat liver preparations. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. RP JamisDow, CA (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,OFF RES RESOURCES,4 RES COURT,ROOM 314,ROCKVILLE,MD 20850, USA. NR 30 TC 53 Z9 55 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1995 VL 36 IS 2 BP 107 EP 114 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QY585 UT WOS:A1995QY58500003 PM 7767945 ER PT J AU Blaney, SM Cole, DE Godwin, K Sung, C Poplack, DG Balis, FM AF Blaney, SM Cole, DE Godwin, K Sung, C Poplack, DG Balis, FM TI Intrathecal administration of topotecan in nonhuman primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE topotecan; meningeal malignancies; intrathecal ID CEREBROSPINAL-FLUID; PHASE-I AB The cerebrospinal fluid (CSF) pharmacokinetics of topotecan were studied in a nonhuman primate model following intraventricular administration of 0.1 mg. Lactone and total drug concentrations were measured using a reverse-phase HPLC method with fluorescence detection. The mean peak concentrations of lactone and total drug in ventricular CSF were 83 +/- 18 mu M and 88 +/- 25 mu M, respectively. CSF drug elimination of the lactone was bi-exponential with a terminal half-life of 1.3 h. The mean clearance from ventricular CSF was 0.075 ml/min for the lactone and 0.043 ml/min for total drug. The ventricular CSF drug exposure (AUC) to lactone was 450-fold greater following intraventricular administration of 0.1 mg topotecan than after systemic intravenous administration of a 40-fold higher dose (10 mg/m(2)). Peak lumbar concentrations (n = 1), which occurred 2 h after intraventricular drug administration, were 0.98 mu M and 2.95 mu M for the lactone and total drug, respectively. A transient CSF pleocytosis was observed in one animal following intraventricular topotecan administration and in one animal following intralumbar topotecan administration. No other acute or chronic neurologic or systemic toxicities were observed following a single intraventricular dose or weekly (x4) intralumbar topotecan. Compared with systemic topotecan, intrathecal administration provided a significant pharmacokinetic advantage in terms of CSF drug exposure and did not produce any significant neurotoxicity in a nonhuman primate model. Intrathecal topotecan should be evaluated clinically as a potential alternative therapy for refractory meningeal tumors. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. RP Blaney, SM (reprint author), WALTER REED ARMY MED CTR,WASHINGTON,DC 20307, USA. NR 15 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1995 VL 36 IS 2 BP 121 EP 124 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QY585 UT WOS:A1995QY58500005 PM 7767947 ER PT J AU ROTHMAN, N STEWART, WF PAUL, A AF ROTHMAN, N STEWART, WF PAUL, A TI INCORPORATING BIOMARKERS INTO CANCER-EPIDEMIOLOGY - A MATRIX OF BIOMARKER AND STUDY DESIGN CATEGORIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HYDROCARBON-DNA ADDUCTS; AFLATOXIN BIOMARKERS; BIOLOGIC MARKERS; LUNG-CANCER; MOLECULAR EPIDEMIOLOGY; GENETIC SUSCEPTIBILITY; BREAST-CANCER; P53 MUTATIONS; ISSUES; VALIDATION AB During the last decade, there has been increasing interest in the use of biomarkers in cancer epidemiology to enhance exposure assessment, to gain insight into disease mechanism, and to understand acquired or inherited susceptibility. To facilitate the use of biomarkers in health research, biomarkers have been divided into categories that depict the spectrum of cancer pathogenesis from exposure to disease. In this paper, we consider the epidemiological designs most suitable for the study of each type of marker. In particular, we present a two-dimensional matrix relating the biomarker categories on one axis to four different types of activities (laboratory, transitional, and etiological studies and public health applications) that develop markers and apply them in human populations. We then use the matrix to review the potential application of biomarkers in observational studies of cancer etiology, discussing the advantages, disadvantages, and logistical considerations in using biomarkers to answer research questions. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. NIOSH,SCREENING & NOTIFIC SECT,CINCINNATI,OH 45226. RP ROTHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EPN 418,6130 EXECUT BLVD,MSC 7364,BETHESDA,MD 20892, USA. NR 70 TC 67 Z9 68 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1995 VL 4 IS 4 BP 301 EP 311 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RC372 UT WOS:A1995RC37200001 PM 7655323 ER PT J AU CHOW, WH MCLAUGHLIN, JK MANDEL, JS WACHOLDER, S NIWA, S FRAUMENI, JF AF CHOW, WH MCLAUGHLIN, JK MANDEL, JS WACHOLDER, S NIWA, S FRAUMENI, JF TI RISK OF RENAL-CELL CANCER IN RELATION TO DIURETICS, ANTIHYPERTENSIVE DRUGS, AND HYPERTENSION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BLOOD-PRESSURE; KIDNEY CANCER; CARCINOMA; MORTALITY; OBESITY AB Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor, In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications, Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension, After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3), The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product, Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs, Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer, Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk, These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events, Further large scale studies should be considered, especially in populations that have regular blood pressure measurements and more detailed documentation of medication use. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. WESTAT CORP,ROCKVILLE,MD 20850. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN-415,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 28 TC 39 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1995 VL 4 IS 4 BP 327 EP 331 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RC372 UT WOS:A1995RC37200004 PM 7655326 ER PT J AU DORGAN, JF REICHMAN, ME JUDD, JT BROWN, C LONGCOPE, C SCHATZKIN, A CAMPBELL, WS FRANZ, C KAHLE, L TAYLOR, PR AF DORGAN, JF REICHMAN, ME JUDD, JT BROWN, C LONGCOPE, C SCHATZKIN, A CAMPBELL, WS FRANZ, C KAHLE, L TAYLOR, PR TI RELATIONSHIPS OF AGE AND REPRODUCTIVE CHARACTERISTICS WITH PLASMA ESTROGENS AND ANDROGENS IN PREMENOPAUSAL WOMEN SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; HORMONE-BINDING GLOBULIN; 1ST BIRTH; MENSTRUAL FACTORS; MENARCHE; PARITY; POPULATION; MENOPAUSE; ASSOCIATIONS; ENVIRONMENT AB We used data from a cross-sectional study of 107 premenopausal women to evaluate the relation of age, menarcheal age, parity, and age at first live birth with plasma estrogen and androgen levels in premenopausal women, Fasting blood specimens were collected on each of days 5-7, 12-15, and 21-23 of menstrual cycles of the participants and pooled to create follicular, midcycle, and luteal phase samples, respectively, for each woman, Age was associated significantly and positively with plasma estradiol levels during the follicular phase [percentage difference/year = 2.6; 95% confidence interval (CI) = 1.0-4.2] and midcycle (percentage difference/year = 2.7; 95% CI = 0.9-4.7) but not the luteal phase (percentage difference/year = -0.4; 95% CI = -1.9-1.3) of the menstrual cycle, The relation of age to plasma estradiol varied by parity, with significant interactions during midcycle and luteal phase, Among nulliparous women, plasma estradiol levels increased with age midcycle and during the luteal phase, but among parous women estradiol levels decreased with age during these phases of the menstrual cycle, Plasma estrone increased with age in all women during the follicular phase of the menstrual cycle (percentage difference/year = 1.5; 95% CI = 0.2-2.8), During the luteal phase there was a significant interaction with parity; estrone levels in nulliparous women varied only slightly with age, but levels in parous women decreased significantly as age increased, The androgens, androstenedione and dehydroepiandrosterone sulfate decreased, and sex hormone-binding globulin increased as age increased, The results of this cross-sectional study suggest that pregnancy may modify age-related changes in plasma estrogen levels. C1 USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01655. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP DORGAN, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,6130 EXECUT BLVD,EPN,ROOM 211,ROCKVILLE,MD 20852, USA. NR 44 TC 70 Z9 70 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1995 VL 4 IS 4 BP 381 EP 386 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RC372 UT WOS:A1995RC37200012 PM 7655334 ER PT J AU OSHIRO, EM VIOLA, JJ OLDFIELD, EH WALBRIDGE, S BACHER, J FRANK, JA BLAESE, RM RAM, Z AF OSHIRO, EM VIOLA, JJ OLDFIELD, EH WALBRIDGE, S BACHER, J FRANK, JA BLAESE, RM RAM, Z TI TOXICITY STUDIES AND DISTRIBUTION DYNAMICS OF RETROVIRAL VECTORS FOLLOWING INTRATHECAL ADMINISTRATION OF RETROVIRAL VECTOR-PRODUCER CELLS SO CANCER GENE THERAPY LA English DT Article DE GENE TRANSFER; RETROVIRAL VECTOR; LEPTOMENINGEAL CARCINOMATOSIS; THYMIDINE KINASE; RAF; PRIMATE ID MEDIATED GENE-TRANSFER; MENINGEAL CARCINOMATOSIS; BRAIN-TUMORS; BREAST-CANCER; METASTASES; DIAGNOSIS; LEUKEMIA; LUNG; RAT AB The use of intrathecal, retroviral-mediated transfer of the herpes simplex thymidine kinase (HStk) gene and subsequent ganciclovir (GCV) administration has recently been shown to improve survival in a rat model of leptomeningeal carcinomatosis. Clinical application of this approach is attractive because access to the cerebrospinal fluid (CSF) space is relatively noninvasive and distribution of producer cells and vectors may be facilitated by circulation of CSF, overcoming distribution problems inherent in solid tumors. However, meningeal inflammation, transduction and injury to normal CNS tissue, proliferation of the xenogeneic producer cells in the subarachnoid space, immune-mediated injury, and development of hydrocephalus are possible complications of intraventricular or intrathecal administration of vector-producer cells. In addition, the dynamics of producer cell and vector distribution in the CSF are unknown. To address these issues, we evaluated the safety of this approach for gene delivery and assessed the dynamics of distribution of producer cells and retroviral vectors in rats and non-human primates. In rats, transduction of normal central nervous system (CNS) structures surrounding the subarachnoid space was evaluated after intrathecal and intraventricular injections of beta-galactosidase and HStk vector-producer cells, with and without GCV. In primates, beta-galactosidase and HStk vector-producer cells were injected intraventricularly and GCV was administered either intrathecally or intravenously. Toxicity was evaluated by neurologic examination, serial gadolinium-enhanced MRI scans of the brain, and blood and CSF profiles. A subgroup of monkeys received repeated intraventricular injection of vector-producer cells and intravenous GCV. The titer of retroviral-vector was measured in cisternal and lumbar CSF samples after repeated producer cell injection. With the exception of the choroid plexus, no evidence of transduction of normal CNS structures occurred. No clinical toxicity or histologic abnormalities were observed in rats or primates. The choroid plexus had evidence of damage after either systemic or intraventricular administration of GCV. However, no evidence of clinical toxicity accompanied these changes. Blood and CSF profiles and MRI brain scans performed in the primates remained normal throughout the study. Free retroviral particles were detected in similar titers in the cisternal and lumbar CSF samples one day after cell injections, but were not detected at later intervals. Intrathecal administration of HStk vector-producer cells and treatment with GCV is not associated with significant toxicity. Intraventricular injection of vector-producer cells results in release of viable genetic vectors in the CSF that circulate through the ventricular and subarachnoid space. C1 NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NCI, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. NCI, DIAGNOST RADIOL RES PROGRAM, BETHESDA, MD 20892 USA. NCI, METAB BRANCH, BETHESDA, MD 20892 USA. NR 34 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUN PY 1995 VL 2 IS 2 BP 87 EP 95 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA RG600 UT WOS:A1995RG60000001 PM 7621261 ER PT J AU KASHUBA, VI SZELES, A ALLIKMETS, R NILSSON, AS BERGERHEIM, USR MODI, W GRAFODATSKY, A DEAN, M STANBRIDGE, EJ WINBERG, G KLEIN, G ZABAROVSKY, ER AF KASHUBA, VI SZELES, A ALLIKMETS, R NILSSON, AS BERGERHEIM, USR MODI, W GRAFODATSKY, A DEAN, M STANBRIDGE, EJ WINBERG, G KLEIN, G ZABAROVSKY, ER TI A GROUP OF NOTI JUMPING AND LINKING CLONES COVER 2.5 MB IN THE 3P21-P22 REGION SUSPECTED TO CONTAIN A TUMOR-SUPPRESSOR GENE SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID RENAL-CELL CARCINOMA; LUNG-CANCER; HUMAN GENOME; CPG ISLANDS; SHORT ARM; DELETION; CHROMOSOME-3; HETEROZYGOSITY; MARKERS; 3P AB The chromosomal region 3p21.2-p22 has been shown to be involved in the development of several forms of solid tumors. Such deletions, translocations, and rearrangements presumably result in the disturbance or loss of a critical gene function. Pulsed-field gel electrophoresis (PFGE), using NotI linking clones as a probe represent a powerful tool for analyzing such rearrangements. A NotI linking clone, AP20 (D3S1641), was localized by in situ hybridization to 3p21.3-p22. Two NotI jumping clones adjacent to this clone were isolated, clone J32-612 covering 0.5 Mb and clone J31-611 covering approximately 1 Mb. Clone J31-611 crosses the border of the deletion present in hybrid cell line MCH939.2, which contains a deleted 3p21 region. For these jumping clones, corresponding NotI linking clones, NLJ3 (D3S1642) and NL3-003, were isolated. Altogether, Linking and jumping clones from the AP20 locus hybridize to NotI fragments totaling 2.5 Mb in length. These NotI-containing clones defect expressed sequences in several human tissues. Clone NLJ3 possesses homology to the human platelet-derived endothelial cell growth factor gene and may represent a new member of this gene family Another done (AP20) revealed 66% sequence similarity to rat skeletal muscle voltage-sensitive sodium channel subtype 2. Therefore, this group of clones will be useful not only for analyzing rearrangements in tumors, but also for the isolation of new genes from the 3p21.3-p22 region. C1 KAROLINSKA INST,DEPT TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,KIEV,UKRAINE. NCI,FREDERICK CANC RES & DEV CTR,VIROL CANCEROGENESIS LAB,FREDERICK,MD. KAROLINSKA INST,DEPT UROL,STOCKHOLM,SWEDEN. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RUSSIAN ACAD SCI,INST CYTOL & GENET,SIBERIAN BRANCH,NOVOSIBIRSK,RUSSIA. CALIF COLL MED,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA. RUSSIAN ACAD SCI,ENGELHARDT INST MOLEC BIOL,MOSCOW,RUSSIA. RI Zabarovsky, Eugene/A-6645-2010; Dean, Michael/G-8172-2012; Winberg, Gosta/I-5686-2013; Graphodatsky, Alexander/B-4922-2010; OI Dean, Michael/0000-0003-2234-0631; Graphodatsky, Alexander/0000-0002-8282-1085; Winberg, Gosta/0000-0002-3371-4056 FU NCI NIH HHS [5 RO1 CA14054-15] NR 39 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1995 VL 81 IS 2 BP 144 EP 150 DI 10.1016/0165-4608(94)00215-W PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RM128 UT WOS:A1995RM12800008 PM 7621411 ER PT J AU HERNANDEZ, L CHOLODY, WM HUDSON, EA RESAU, JH PAULY, G MICHEJDA, CJ AF HERNANDEZ, L CHOLODY, WM HUDSON, EA RESAU, JH PAULY, G MICHEJDA, CJ TI MECHANISM OF ACTION OF BISIMIDAZOACRIDONES, NEW DRUGS WITH POTENT, SELECTIVE ACTIVITY AGAINST COLON-CANCER SO CANCER RESEARCH LA English DT Article ID MITOCHONDRIAL-DNA; BIFUNCTIONAL INTERCALATORS; RNA-SYNTHESIS; CELL-LINES; DHFR GENE; REPAIR; DITERCALINIUM; BINDING; RECOGNITION; CARCINOMA AB Antitumor bisimidazoacridones are bifunctional DNA binders which have recently been shown to selectively target human colon carcinoma cells in vitro and in vivo and appear to be excellent candidates for clinical development. We have studied the mechanism of action of one bisimidazoacridone, WMC26, which is 1,000-10,000 times more toxic to human colon carcinoma cells (HCT116) than to melanoma cells (SKMEL2) in vitro. Plasmid DNA exposed to WMC26 showed enhanced digestion by DNase I at A-T-rich sites, suggesting alterations in DNA conformation upon drug binding. These results led us to investigate whether WMC26 was selectively toxic due to a specific recognition of DNA bends by repair excinucleases, as has been demonstrated with the DNA bisintercalator, ditercalinium. Both prokaryotic and eukaryotic cells with intact repair capacity were shown to be selectively sensitive to WMC26, strongly indicating that excision repair plays a role in its toxicity. Confocal microscopy studies utilizing fluorescence of the WMC26 chromophore showed compound localization in the perinuclear cytoplasmic area, as had been previously noted for ditercalinium, indicating that cytoplasmic DNA could be the target, This irreversible accumulation of compound was gradually followed by vacuolization of the cytoplasm and cell death. Cell cycle analysis of both lines treated with WMC26 or with ditercalinium showed that, while the latter induced HCT116 growth arrest at G(1)-G(0), WMC26 also blocked the cell cycle at G(2)-M; SKMEL2 cells did not undergo any changes in cell cycle as a result of either treatment. Our data show that WMC26 is 10-100 times more cytotoxic than ditercalinium in vitro. Like ditercalinium, WMC26 appears to exert its toxicity via cytoplasmic elements, through a mechanism involving excision repair processes. However, its highly selective cytotoxicity may stem from additional undefined targets in sensitive colon cancer cells. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MACROMOLEC STRUCT LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-46000] NR 42 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1995 VL 55 IS 11 BP 2338 EP 2345 PG 8 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500023 PM 7757985 ER PT J AU COHEN, PS LETTERIO, JJ GAETANO, C CHAN, J MATSUMOTO, K SPORN, MB THIELE, CJ AF COHEN, PS LETTERIO, JJ GAETANO, C CHAN, J MATSUMOTO, K SPORN, MB THIELE, CJ TI INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND ITS RECEPTORS DURING ALL-TRANS-RETINOIC ACID (RA) TREATMENT OF RA-RESPONSIVE HUMAN NEUROBLASTOMA CELL-LINES SO CANCER RESEARCH LA English DT Article ID HUMAN NEURO-BLASTOMA; POLYMERASE CHAIN-REACTION; II RECEPTOR; EXPRESSION CLONING; FALSE POSITIVES; DIFFERENTIATION; INHIBITION; FACTOR-BETA-1; INVITRO; COMPLEX AB Recent work on a variety of normal and malignant cell lines has shown that induction and secretion of biologically active TGF-beta may occur after exposure to all-trans-retinoic acid (RA), coincident with decreased growth rate and/or differentiation. This study evaluates the expression and regulation of transforming growth factor beta (TGF-beta) and its receptors during RA-induced cell growth arrest and induction of differentiation in the RA-sensitive human neuroblastoma cell line SMS-KCNR and the RA-resistant neuroblastoma cell line SK-N-AS. RA treatment of SMS-KCNR cells results in a 40-fold increase in TGF-beta 1 mRNA after 4 days of RA, a dose-dependent increase in TGF-beta 1 secretion, an increase in types I (TBR(I)) and III (TBR(III)) TGF-beta receptor proteins, and an increase in type II TGF-beta receptor (TBR(II)) mRNA coincident with RA-responsiveness of the cells. However, in the RA-resistant line SK-N-AS, TGF-beta 1 is constitutively secreted at levels that are unchanged after RA treatment, and although TBR(I) and TBR(III) mRNA is expressed in untreated SK-N-AS cells, levels of TBR(I) and TBR(III) protein and TBR(II) mRNA decrease after RA treatment. Thus, in RA-sensitive neuroblastoma cells, RA treatment may result in the induction of a negative autocrine TGF-beta 1 growth regulatory loop. These results suggest the hypothesis that: (a) induction of a TGF-beta 1 negative autocrine growth loop may be a necessary component for RA-responsiveness of neuroblastoma cells in vivo; and (b) the inability to induce or maintain this TGF-beta 1 negative autocrine growth loop may be a mechanism of RA resistance in neuroblastoma. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,HARBOR MED CTR,INST RES & EDUC,TORRANCE,CA 90509. NCI,PEDIAT BRANCH,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,MOLEC BIOL SECT,BETHESDA,MD 20892. NR 49 TC 57 Z9 57 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 JUN 1 PY 1995 VL 55 IS 11 BP 2380 EP 2386 PG 7 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500029 PM 7757990 ER PT J AU BAE, IS FAN, SJ BHATIA, K KOHN, KW FORNACE, AJ OCONNOR, PM AF BAE, IS FAN, SJ BHATIA, K KOHN, KW FORNACE, AJ OCONNOR, PM TI RELATIONSHIPS BETWEEN G(1) ARREST AND STABILITY OF THE P53 AND P21(CIP1/WAF1) PROTEINS FOLLOWING GAMMA-IRRADIATION OF HUMAN LYMPHOMA-CELLS SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; DNA-DAMAGING AGENTS; GENE AMPLIFICATION; IONIZING-RADIATION; CELLULAR-RESPONSE; GADD45 GENE; MUTANT P53; RNA; CHECKPOINTS AB We investigated temporal relationships between ionizing radiation-induced G(1) arrest and induction of the p53-regulated genes GADD45, CIP1/WAF1, and MDM2 in a series of Burkitt's lymphoma and lymphoblastoid cell lines that differed in p53 gene status. Emphasis was placed on characterization of the EW36 cell line, which despite expressing wild-type p53 genes, is defective in G(1) arrest following gamma-irradiation (P. M. O'Connor et al., Cancer Res., 53: 4776-4780, 1993). Induction of CIP1/ WAF1, GADD45, and to a lesser extent MDM2 mRNA was observed in all wild-type p53 lines that arrested in G(1). Cell lines that contained only mutant p53 genes or were heterozygous for p53 mutations failed to induce appreciable levels of these p53-regulated transcripts and did not arrest in G(1).G(1) arrest in the wild-type p53 cell line WMN was more prolonged than elevation of CIP1/WAF1, GADD45, or MDM2 transcripts, suggesting that G(1) arrest duration must be dependent upon stability of these newly synthesized proteins. In agreement, we found that p21(Cip1/Waf1), a potent inhibitor of G(1)-S phase cyclin-dependent kinases, was maintained at elevated levels throughout the period that WMN cells remained arrested in G(1). EW36 cells exhibited normal induction of CIP1/WAF1, GADD45, and MDM2 mRNA following gamma-irradiation, suggesting that the defect in G(1) arrest must reside downstream of p53 transactivation. Investigations into the stability of p53 and p21(Cip1/Waf1) revealed that EW36 cells failed to maintain elevated levels of these proteins following irradiation. p53 levels decreased within 4 h of irradiation, and p21(Cip1/Waf1) levels decreased shortly after the normal decline of CIP1/WAF1 mRNA levels. Degradation of p21(Cip1/Waf1) coincided with the escape of EW36 cells from G(1) arrest. Our studies suggest that p21(Cip1/Waf1) stability may determine G(1) arrest duration and that premature degradation of this protein could provide an alternative route to subversion of the G(1) checkpoint in cancer cells. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 55 TC 116 Z9 119 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1995 VL 55 IS 11 BP 2387 EP 2393 PG 7 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500030 PM 7757991 ER PT J AU KARR, JF KANTOR, JA HAND, PH EGGENSPERGER, DL SCHLOM, J AF KARR, JF KANTOR, JA HAND, PH EGGENSPERGER, DL SCHLOM, J TI THE PRESENCE OF PROSTATE-SPECIFIC ANTIGEN-RELATED GENES IN PRIMATES AND THE EXPRESSION OF RECOMBINANT HUMAN PROSTATE-SPECIFIC ANTIGEN IN A TRANSFECTED MURINE CELL-LINE SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN GLANDULAR KALLIKREIN; CANCER; CARCINOMA; CDNA; ANTIBODY; MARKER; ADENOCARCINOMA; SEQUENCE; PROTEIN AB Human prostate-specific antigen (PSA) has been shown as an aid in the early detection of prostate cancer (W. J. Catalona et al., J. Am. Med. Assoc., 270: 948-954, 1993) and was approved in 1994 by the Food and Drug Administration for early detection of prostate cancer. Immunotherapies directed against PSA have been suggested in patients with metastatic prostate cancer. One of the essential questions is to define which nonhuman species express PSA for experimental studies. Using Southern blot analyses, genes related to human PSA have been detected in several nonhuman primate species, including chimpanzee, orangutan, gorilla, macaque, and rhesus monkey, but not in other mammalian species, including rabbit, cow, pig, dog, rat, or mouse. Immunohistochemical staining with anti-human PSA antisera detected strong staining in both human and monkey prostatic epithelial cells with no reactivity to rat prostate cells. Because the PSA gene is not present in the murine genome, a matched set of murine cell lines has been developed that may be useful to study the biochemical functions of PSA and as an experimental target for PSA-directed immunotherapy. To establish such cell lines, a C57BL/6 murine colon adenocarcinoma cell line, MC-38, was transfected with a retroviral vector containing cDNA encoding the human PSA gene. Genetic analysis of a PSA-secreting clone, PSA/MC-38, demonstrated that the PSA gene had been stably integrated into the MC-38 genome. The PSA/MC-38 cell line was found to secrete PSA into tissue culture medium, producing a protein of approximately M(r) 30,000. In vivo, PSA/MC-38 grew as a s.c. tumor in male and female mice. PSA/MC-38 tumors grew more rapidly in athymic mice than in syngeneic C57BL/6 mice, and in both mouse strains, the PSA/MC-38 tumors grew more slowly than control vector-transduced tumors. PSA was detected in the serum and tumors of PSA/MC-38 tumor-bearing mice. It is proposed that PSA/MC-38 cells may be used as a murine tumor model to test potential therapeutic vaccines and other experimental therapies directed against PSA. C1 NCI,DIV CANC BIOL DIAG & CTR,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 48 TC 48 Z9 49 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 JUN 1 PY 1995 VL 55 IS 11 BP 2455 EP 2462 PG 8 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500040 PM 7538903 ER PT J AU BRESALIER, RS SCHWARTZ, B KIM, YS DUH, QY KLEINMAN, HK SULLAM, PM AF BRESALIER, RS SCHWARTZ, B KIM, YS DUH, QY KLEINMAN, HK SULLAM, PM TI THE LAMININ ALPHA-1 CHAIN ILE-LYS-VAL-ALA-VAL (IKVAV)-CONTAINING PEPTIDE PROMOTES LIVER COLONIZATION BY HUMAN COLON-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID AMINO-ACID-SEQUENCE; MELANOMA-CELLS; TUMOR-GROWTH; A-CHAIN; SYNTHETIC PEPTIDE; BINDING PROTEIN; METASTASIS; IDENTIFICATION; ATTACHMENT; RECEPTOR AB Laminin, a major basement membrane-specific glycoprotein, promotes the attachment, migration, and invasion of a variety of tumor cells. Since laminin is present in the perisinusoidal matrix of the liver, we studied its effects on liver colonization by human colon cancer cells (HM7, LiM6) previously shown to have liver-metastasizing ability in athymic mice. These malignant cells expressed high levels of a 32-kDa laminin-binding protein on Western blot analysis when compared to the low metastatic parental cell line. Coinjection of laminin cu chain-derived peptides which contain the amino acid sequence Ile-Lys-Val-Ala-Val (IKVAV) significantly stimulated liver colonization as determined by liver weight (P < 0.005) and number of tumor nodules (P < 0.02) 3 weeks after splenic-portal inoculation into nude mice. No stimulation was seen with a control peptide containing the same amino acids but in a scrambled sequence, In contrast, the Tyr-Ile-Gly-Ser-Arg peptide from the laminin beta 1 chain significantly inhibited HM7 liver colonization. These differences were not due to alterations in the number of cells initially reaching the liver as determined by injection of [I-125]iododeoxyuridine-labeled tumor cells, but retention in the liver was stimulated by the IKVAV-containing peptides. Flow analysis indicated that the IKVAV peptide may act, in part, by stimulating homotypic adhesion of tumor cells. These data suggest that interactions of colon cancer cells with the IKVAV site on laminin may play a role in the formation of metastatic foci in the liver through cell-cell or cell-substratum interactions which promote metastasis. C1 UNIV MICHIGAN,SCH MED,DEPT MED,ANN ARBOR,MI 48109. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94121. UNIV CALIF SAN FRANCISCO,DEPT VET AFFAIRS MED CTR,SAN FRANCISCO,CA 94121. NIDR,BETHESDA,MD 20892. RP BRESALIER, RS (reprint author), HENRY FORD HLTH SCI CTR,GASTROINTESTINAL CANC RES LAB,2799 W GRAND BLVD,DETROIT,MI 48202, USA. NR 30 TC 30 Z9 30 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1995 VL 55 IS 11 BP 2476 EP 2480 PG 5 WC Oncology SC Oncology GA RA145 UT WOS:A1995RA14500043 PM 7758002 ER PT J AU WALKER, NJ GASTEL, JA COSTA, LT CLARK, GC LUCIER, GW SUTTER, TR AF WALKER, NJ GASTEL, JA COSTA, LT CLARK, GC LUCIER, GW SUTTER, TR TI RAT CYP1B1 - AN ADRENAL CYTOCHROME-P450 THAT EXHIBITS SEX-DEPENDENT EXPRESSION IN LIVERS AND KIDNEYS OF TCDD-TREATED ANIMALS SO CARCINOGENESIS LA English DT Article ID AROMATIC HYDROCARBON METABOLISM; POST-TRANSCRIPTIONAL REGULATION; DIBENZO-P-DIOXINS; GENE-EXPRESSION; AH-RECEPTOR; INDUCIBLE CYTOCHROME-P450; CELL-PROLIFERATION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; DNA; MICROSOMES AB The broad spectrum of biological responses associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is believed to be due to the alteration in expression of TCDD-inducible genes. The aim of this study was to investigate the effects of TCDD on the in vivo tissue-specific expression of the recently identified TCDD-inducible cytochrome P450 CYP1B1 [Sutter et al, (1994) J. Biol. Chem., 269, 13092-13099] in Sprague-Dawley rats. We cloned the 5.0 kb rat homolog of CYP1B1 from a TCDD-treated rat liver cDNA library and showed that the rat and human CYP1B1 predicted amino acid sequences are 80% identical. RNA hybridization analysis showed that CYP1B1 is constitutively expressed in the adrenal glands and also in the testes of untreated rats. This tissue distribution suggests that CYP1B1 may be a physiological steroid hydroxylase. Seventy-two hours post-administration of 25 mu g/kg body wt TCDD by gavage, steady-state levels of the 5.1 kb CYP1B1 RNA were increased > 50-fold in liver, and to a lesser extent in kidneys, lung, heart and ovaries. Average CYP1B1 RNA levels were significantly higher in the kidneys and livers of TCDD-treated females than in those from similarly treated males. In contrast, no significant sex-difference was observed in the levels of CYP1A1 in these tissues in TCDD-treated animals. In Sprague-Dawley rats, TCDD is a more potent hepatocarcinogen in females than in males. The induction of CYP1B1 in TCDD rat liver may be a contributing factor to the carcinogenic action of this persistent environmental pollutant. C1 JOHNS HOPKINS UNIV HOSP,SCH HYG & PUBL HLTH,JOHNS HOPKINS MED INST,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS NIH HHS [ES03819, ES07141] NR 60 TC 99 Z9 102 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 JUN PY 1995 VL 16 IS 6 BP 1319 EP 1327 DI 10.1093/carcin/16.6.1319 PG 9 WC Oncology SC Oncology GA RE774 UT WOS:A1995RE77400010 PM 7788849 ER PT J AU TSUTSUI, T KOMINE, A HUFF, J BARRETT, JC AF TSUTSUI, T KOMINE, A HUFF, J BARRETT, JC TI EFFECTS OF TESTOSTERONE, TESTOSTERONE PROPIONATE, 17-BETA-TRENBOLONE AND PROGESTERONE ON CELL-TRANSFORMATION AND MUTAGENESIS IN SYRIAN-HAMSTER EMBRYO CELLS SO CARCINOGENESIS LA English DT Article ID NEOPLASTIC TRANSFORMATION; INDUCTION; CULTURE; DIETHYLSTILBESTROL; TRENBOLONE; ANEUPLOIDY; MUTATIONS AB Testosterone, testosterone propionate, 17 beta-trenbolone and progesterone, which represent the main endogenous and synthetic androgens and a progestin, were evaluated for possible cell transformation and genetic effects in Syrian hamster embryo (SHE) cells. Cell growth was reduced by treatment with the steroids at 10-30 mu g/ml in a dose-related manner. Testosterone and testosterone propionate were less toxic than the other two steroids. Testosterone, testosterone propionate and progesterone induced morphological transformation of SHE cells with similar transformation frequencies. The most potent effects were observed with testosterone propionate, which induced cell transformation at 1-30 mu g/ml in a dose-related manner. Testosterone and progesterone transformed cells only at the highest dose (30 mu g/ml). 17 beta-Trenbolone did not induce a statistically significant level of cell transformations at any dose tested (up to 30 mu g/ml). The transformation frequencies induced by testosterone, testosterone propionate and progesterone were less than one-half that induced, by benzo[a]pyrene at 1 mu g/ml. None of these steroids induced significant increases in frequencies of chromosome aberrations or aneuploidy, Gene mutations were not observed for testosterone at the HPRT or Na+/K+ GTPase locus. Because these steroids are also associated with carcinogenic activity in vivo, these in vitro findings provide a model and new insights into the study of the mechanisms of androgen- and progestin-induced cell transformation. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIPPON DENT UNIV TOKYO,SCH DENT TOKYO,DEPT PHARMACOL,CHIYODA KU,TOKYO 102,JAPAN. NR 25 TC 8 Z9 8 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 JUN PY 1995 VL 16 IS 6 BP 1329 EP 1333 DI 10.1093/carcin/16.6.1329 PG 5 WC Oncology SC Oncology GA RE774 UT WOS:A1995RE77400011 PM 7788850 ER PT J AU BEEBE, LE ANVER, MR RIGGS, CW FORNWALD, LW ANDERSON, LM AF BEEBE, LE ANVER, MR RIGGS, CW FORNWALD, LW ANDERSON, LM TI PROMOTION OF N-NITROSODIMETHYLAMINE-INITIATED MOUSE LUNG-TUMORS FOLLOWING SINGLE OR MULTIPLE LOW-DOSE EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN SO CARCINOGENESIS LA English DT Article ID AROMATIC-HYDROCARBONS; MICE; TCDD; TOXICITY; CANCER; LIVER AB The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is highly toxic to several rodent species and may have adverse health effects in exposed human populations. Further, TCDD has been shown to be a potent liver tumor promoter in the rat after repeated administration. These studies were conducted to determine the tumor promoting capability of TCDD in the Swiss mouse following single or multiple exposures. Following tumor initiation with N-nitrosodimethylamine (NDMA; 25 mg/kg), animals were given either a single dose (1.6, 16 or 48 mu g/kg) or repeated injections (0.05 mu g/kg/week for 20 weeks) of TCDD and sacrificed at 52 weeks of age. Neither NDMA nor TCDD caused an increase in incidence of liver tumors. NDMA induced lung tumors in 100% of animals, with 12 +/- 0.1 tumors/mouse. The multiplicity of lung tumors was significantly increased by low dose TCDD treatment, with 20 +/- 2.6 tumors/mouse following a single 1.6 mu g/kg dose (P = 0.016) and 18 +/- 1.7 (P = 0.031) following repeated 0.05 mu g/kg doses (x20). Higher doses of TCDD did not increase multiplicity of lung tumors and, in fact, may have been toxic to the lungs of NDMA-treated mice, as evidenced by the infiltration of pigmented macrophages. These data demonstrate the potent tumor promoting capability of TCDD in mouse lung. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP BEEBE, LE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 26 TC 21 Z9 24 U1 1 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 JUN PY 1995 VL 16 IS 6 BP 1345 EP 1349 DI 10.1093/carcin/16.6.1345 PG 5 WC Oncology SC Oncology GA RE774 UT WOS:A1995RE77400014 PM 7788853 ER PT J AU SNYDERWINE, EG WELTI, DH DAVIS, CD FAY, LB TURESKY, RJ AF SNYDERWINE, EG WELTI, DH DAVIS, CD FAY, LB TURESKY, RJ TI METABOLISM OF THE FOOD-DERIVED CARCINOGEN 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE (MEIQX) IN NONHUMAN-PRIMATES SO CARCINOGENESIS LA English DT Article ID HUMAN-LIVER; SALMONELLA-TYPHIMURIUM; HETEROCYCLIC AMINES; MAJOR METABOLITE; AROMATIC-AMINES; N-OXIDATION; RAT; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; DNA; IDENTIFICATION AB The metabolism and disposition of the food mutagen and rodent carcinogen 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline was investigated in cynomolgus monkeys. Monkeys were administered a single dose of radiolabeled [C-14]MeIQx (2.2 or 50 mu mol/kg). Peak blood levels of radioactivity were observed within 1-3 h after dosing and declined rapidly thereafter. By 72 h after dosing, approximately 50% and 70% of the 2.2 mu mol/kg, and 50 mu mol/kg dose, respectively, was excreted in the urine. Approximately 15-20% of either dose was recovered in the feces. Eight metabolites and the parent compound were detected in urine by HPLC. The parent compound accounted for similar to 15-25% of the dose excreted in the urine, Seven MeIQx urinary metabolites were identified. Five metabolites were identical to MeIQx metabolites previously found in rats: MeIQx-N-2-glucuronide, MeIQx-N-2-sulfamate, MeIQx-5-sulfate, MeIQx-5-O-glucuronide, and 8-CH2OH-MeIQx-5-sulfate. Cynomolgus monkeys, however, metabolized MeIQx to a novel glucuronide conjugate of MeIQx not found in rats. Based upon mass spectroscopy and proton NMR analyses, the structure of this metabolite was consistent with an N-1-glucuronide of MeIQx. This metabolite was the major urinary metabolite found in monkeys, accounting for 31-37% of the dose excreted in the urine over a 24 h period. One additional metabolite identified in urine and feces of MeIQx treated cynomolgus monkeys, that has not been found previously in any other animal model, was 7-oxo-MeIQx, a likely enteric bacterial metabolite of MeIQx, 7-Oxo-MeIQx accounted for 20-25% of the dose of MeIQx found in the urine and was the major fecal metabolite. The N-2-glucuronide conjugate of the carcinogenic metabolite 2-hydroxyamino-3,8-dimethylimidazo[4,5-f]quinoxaline (NHOH-MeIQx) was not detected in urine or bile of monkeys, even after 10 daily doses of MeIQx (100 mu mol/kg) were given. The results indicate that MeIQx is metabolically processed in monkeys via multiple pathways of detoxification. However, MeIQx is poorly metabolically activated via cytochrome P450 mediated N-oxidation. The in vivo metabolism of MeIQx in cynomolgus monkeys is different from that of the structurally related food-derived mutagen 2-amino-3 -methylimidazo [4,5-f]quinoline (IQ), which is readily metabolically activated by this species and in contrast to MeIQx, has been shown to be a powerful hepatic carcinogen. C1 NESTEC LTD,RES CTR,CH-1000 LAUSANNE 26,SWITZERLAND. RP SNYDERWINE, EG (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 37 TC 14 Z9 14 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 JUN PY 1995 VL 16 IS 6 BP 1377 EP 1384 DI 10.1093/carcin/16.6.1377 PG 8 WC Oncology SC Oncology GA RE774 UT WOS:A1995RE77400019 PM 7788858 ER PT J AU HUNT, RA CIUFFO, GM SAAVEDRA, JM TUCKER, DC AF HUNT, RA CIUFFO, GM SAAVEDRA, JM TUCKER, DC TI QUANTIFICATION AND LOCALIZATION OF ANGIOTENSIN-II RECEPTORS AND ANGIOTENSIN-CONVERTING ENZYME IN THE DEVELOPING RAT-HEART SO CARDIOVASCULAR RESEARCH LA English DT Article DE ANGIOTENSIN II RECEPTORS; ANGIOTENSIN CONVERTING ENZYME; QUANTITATIVE AUTORADIOGRAPHY; CARDIAC DEVELOPMENT ID SPONTANEOUSLY HYPERTENSIVE RATS; SMOOTH-MUSCLE CELLS; PROTEIN-SYNTHESIS; CARDIAC FIBROBLASTS; CONDUCTION SYSTEM; NEONATAL RAT; HYPERTROPHY; SUBTYPES; EXPRESSION; GROWTH AB Objective: The aim was to determine the quantification and localisation of angiotensin II receptors and angiotensin converting enzyme (ACE) in the developing rat heart. Methods: Quantitative autoradiography was used to determine the density of [I-125]Sar(1)-angiotensin II binding to angiotensin II receptors and the density of [I-125]351A binding to ACE. Results: Angiotensin ii receptors were first detected in the myocardium on embryonic day 14, and reached a maximum density within the first postnatal week. During the perinatal period, the density of angiotensin II receptors was twofold higher in atrial than in ventricular myocardium [27(SEM 7) v 11(1) fmol . mg(-1) protein]. By adulthood, however, the density of angiotensin II receptors did not differ between atria and ventricles. A high density of angiotensin II receptors was first detected in the cardiac vasculature on embryonic day 19, with binding density decreasing during development. During the embryonic and early postnatal periods, most of the binding in the cardiac vasculature was to AT(2) receptors. ACE was first detected in the myocardium on the day of birth, with the density of binding to ACE increasing during development. On postnatal day 56, the density of binding to ACE was fourfold higher in atrial than in ventricular myocardium [99(22) v 22(4) fmol . mg(-1) protein]. A moderate density of binding to ACE was first detected in the cardiac vasculature and heart valves on embryonic day 19, with binding density increasing during development. By adulthood, the density of binding to ACE was 10- to 25-fold higher in the cardiac vasculature and heart valves than in the myocardium. Conclusions: The density of angiotensin II receptors and the density of binding to ACE are developmentally regulated in the heart. Both AT(1) and AT(2) receptors were present in the rat heart by late gestation and could, therefore, mediate the effects of angiotensin II on early cardiac growth and development. C1 UNIV ALABAMA,DEPT PHYSIOL,BIRMINGHAM,AL 35294. NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 42258, HL 39048] NR 45 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUN PY 1995 VL 29 IS 6 BP 834 EP 840 DI 10.1016/S0008-6363(96)88620-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RF789 UT WOS:A1995RF78900018 PM 7656287 ER PT J AU ISAACS, KR WINSKY, L STRAUSS, KI JACOBOWITZ, DM AF ISAACS, KR WINSKY, L STRAUSS, KI JACOBOWITZ, DM TI QUADRUPLE COLOCALIZATION OF CALRETININ, CALCITONIN-GENE-RELATED PEPTIDE, VASOACTIVE-INTESTINAL-PEPTIDE, AND SUBSTANCE-P IN FIBERS WITHIN THE VILLI OF THE RAT INTESTINE SO CELL AND TISSUE RESEARCH LA English DT Article DE CALCIUM-BINDING PROTEINS; MYENTERIC PLEXUS; SUBMUCOSAL PLEXUS; ENTERIC NERVOUS SYSTEM; RAT (ZIVIC MILLER) ID CALCIUM-BINDING PROTEIN; PIG SMALL-INTESTINE; GASTRIC-ACID SECRETION; DORSAL-ROOT GANGLION; IMMUNOHISTOCHEMICAL LOCALIZATION; SENSORY NEURONS; NERVOUS-SYSTEM; HYBRIDIZATION HISTOCHEMISTRY; IMMUNOREACTIVE NEURONS; HIRSCHSPRUNGS-DISEASE AB Double-labeling immunofluorescent histochemistry demonstrates that calretinin, a calcium-binding protein, coexists with calcitonin gene-related peptide, vasoactive intestinal peptide, and substance P in the fibers innervating the lamina propria of the rat intestinal villi. An acetylcholinesterase histochemical stain revealed that the majority of calretinin-containing cells in the myenteric ganglia were cholinergic and that about one half of the submucosal calretinin-containing cells colocalized with acetylcholinesterase. In situ hybridization studies confirmed the presence of calretinin mRNA in the dorsal root ganglia, and a ribonuclease protection assay verified the presence of calretinin message in the intestine. The coexistence of calretinin in calcitoningene-related-peptide-containing cells that also contained substance P and vasoactive intestinal polypeptide in the dorsal root ganglia suggest that these ganglia are the source of the quadruple colocalization within the sensory fibers of the villi. Although the function of calretinin in these nerves is unknown, it is hypothesized that the coexistence of three potent vasodilatory peptides influences the uptake of metabolized food products within the vasculature of the villi. RP ISAACS, KR (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D48,BETHESDA,MD 20892, USA. NR 69 TC 25 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUN PY 1995 VL 280 IS 3 BP 639 EP 651 DI 10.1007/s004410050391 PG 13 WC Cell Biology SC Cell Biology GA RD657 UT WOS:A1995RD65700015 PM 7541720 ER PT J AU GEORGE, AJT TITUS, JA JOST, CR KURUCZ, I PEREZ, P ANDREW, SM NICHOLLS, PJ HUSTON, JS SEGAL, DM AF GEORGE, AJT TITUS, JA JOST, CR KURUCZ, I PEREZ, P ANDREW, SM NICHOLLS, PJ HUSTON, JS SEGAL, DM TI REDIRECTION OF CELLULAR CYTOTOXICITY - A 2-STEP APPROACH USING RECOMBINANT SINGLE-CHAIN FV MOLECULES SO CELL BIOPHYSICS LA English DT Article; Proceedings Paper CT 11th Conference on Advances in the Applications of Monoclonal Antibodies in Clinical Oncology CY MAY 23-26, 1994 CL MOLYVOS, GREECE DE BISPECIFIC ANTIBODY; SINGLE-CHAIN FV; REDIRECTED CELLULAR CYTOTOXICITY; IMMUNOTHERAPY ID ANTI-TARGET CELL; T-CELLS; BISPECIFIC ANTIBODY; IMMUNOGLOBULIN FORMS; FILAMENTOUS PHAGE; ESCHERICHIA-COLI; TUMOR-GROWTH; FRAGMENTS; PROTEINS; HYBRIDOMAS AB In this article the authors discuss an indirect system for redirecting cellular cytotoxicity, which utilizes a ''universal'' bispecific antibody to redirect T-cells to kill cells targeted with single-chain Fv (sFv) fusion proteins that carry a peptide tag recognized by the bispecific antibody. This approach has a number of theoretical advantages in the immunotherapy of cancer. C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT IMMUNOL,LONDON W12 0NN,ENGLAND. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. CREAT BIOMOLECULES INC,HOPKINTON,MA. RI Perez, Pilar/B-4948-2010; OI Perez, Pilar/0000-0003-3557-2247; George, Andrew/0000-0002-2866-0241 NR 39 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0163-4992 J9 CELL BIOPHYS JI Cell Biophys. PD JUN PY 1995 VL 26 IS 3 BP 153 EP 165 PG 13 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA RR078 UT WOS:A1995RR07800002 PM 8521448 ER PT J AU TURLEY, JM FUNAKOSHI, S RUSCETTI, FW KASPER, L MURPHY, WJ LONGO, DL BIRCHENALLROBERTS, MC AF TURLEY, JM FUNAKOSHI, S RUSCETTI, FW KASPER, L MURPHY, WJ LONGO, DL BIRCHENALLROBERTS, MC TI GROWTH-INHIBITION AND APOPTOSIS OF RL HUMAN B-LYMPHOMA-CELLS BY VITAMIN-E SUCCINATE AND RETINOIC ACID - ROLE FOR TRANSFORMING GROWTH-FACTOR-BETA SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PROTEIN-KINASE-C; ALPHA-TOCOPHERYL SUCCINATE; BLOOD MONONUCLEAR-CELLS; B-16 MELANOMA-CELLS; TGF-BETA; IMMUNOGLOBULIN-SYNTHESIS; PROMYELOCYTIC LEUKEMIA; CANCER PREVENTION; HL-60 CELLS; CORD BLOOD AB Vitamin E succinate (VES) and all-trans-retinoic acid (RA) were determined to be growth inhibitory for B lymphoma cells in vitro. RL, an Epstein-Barr virus-negative human cell line, was growth suppressed 87% with VES (5 mu g/ml) and 58% with RA (10(-6)M); both agents blocked the cells in G(1) of the cell cycle. The antiproliferative effect of VES seems to be independent of its potential antioxidant property because both fat- and water-soluble antioxidants were found to have no effect on pL cell proliferation. VES and RA increased IgM antibody concentrations in cell supernatants 5.8- and 9.9-fold, respectively. DNA fragmentation and flow cytometry studies showed VES- and RA-induced apoptosis in RL cells. VES- and RA-treated RL cells gradually underwent apoptosis over time with maximal induction occurring at days 6 and 5 of culture, respectively. A role for transforming growth factor beta in VES- and RA-mediated RL growth suppression is indicated by increased ligand and type II receptor protein expression. Furthermore, neutralizing antibodies to transforming growth factor beta 1 partially blocked the growth suppressive action of both VES and RA, thus suggesting that a TCF-beta autocrine negative loop was involved in VES and RA suppression of RL cell growth. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP TURLEY, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702, USA. NR 66 TC 84 Z9 94 U1 1 U2 4 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 JUN PY 1995 VL 6 IS 6 BP 655 EP 663 PG 9 WC Cell Biology SC Cell Biology GA RC828 UT WOS:A1995RC82800004 PM 7669719 ER PT J AU BEGUINOT, L YAMAZAKI, H PASTAN, I JOHNSON, AC AF BEGUINOT, L YAMAZAKI, H PASTAN, I JOHNSON, AC TI BIOCHEMICAL-CHARACTERIZATION OF HUMAN GCF TRANSCRIPTION FACTOR IN TUMOR-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FACTOR RECEPTOR GENE; REPRESSES TRANSCRIPTION; EXPRESSION SYSTEM; NUCLEAR-PROTEIN; THYROID-HORMONE; PHORBOL ESTERS; VACCINIA VIRUS; FACTOR-I; BINDING; PROMOTER AB GCF is a transcriptional regulator that was found to repress transcription of the epidermal growth factor (EGF) receptor and several other genes and is encoded by a 3-kb mRNA (R. Kageyama and I. Pastan, Cell, 59: 815-825, 1989; A. C. Johnson et al., J. Biol. Chem., 267: 1689-1694, 1992). To identify and characterize the GCF gene product at the cellular level, we have developed antibodies against a bacterially expressed GCF fusion protein. GCF antibodies recognize GCF present in extracts from human cells and causes a ''supershift'' of a protein DNA complex containing a GCF oligonucleotide binding site. The major form of GCF has a molecular weight of approximately M(r) 97,000, identical to that of GCF transiently expressed in CV1 cells by the vaccinia virus system. In addition, other less abundant species with slightly higher and lower apparent molecular weights are specifically recognized, suggesting extensive posttranslational modification. GCF is highly expressed in EGF receptor-negative human cell lines (HUT1O2, U266, and CA46) and in lower amounts in several EGF receptor-expressing cells (KB, A431, TMK, and HeLa). Cell fractionation studies indicate that GCF is predominantly localized in the nucleus. GCF is a stable protein with a relatively long half-life. In addition, GCF is a phosphoprotein, and the phosphorylated form is found to be associated with the nuclear compartment in both HUT102 and KB cells. Phosphorylation occurs on serine and threonine residues and is stimulated by okadaic acid, phorbol myristate acetate, and cyclic AMP, but not vanadate. The effects of phorbol myristate acetate and okadaic acid are less than additive, suggesting stimulation of a similar pathway. These studies provide a useful tool to address the mechanism by which GCF regulates EGF receptor expression in normal and transformed human cells. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 38 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1995 VL 6 IS 6 BP 699 EP 706 PG 8 WC Cell Biology SC Cell Biology GA RC828 UT WOS:A1995RC82800009 PM 7669724 ER PT J AU AMUNDADOTTIR, LT JOHNSON, MD MERLINO, G SMITH, GH DICKSON, RB AF AMUNDADOTTIR, LT JOHNSON, MD MERLINO, G SMITH, GH DICKSON, RB TI SYNERGISTIC INTERACTION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND C-MYC IN MOUSE MAMMARY AND SALIVARY-GLAND TUMORIGENESIS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN-BREAST-CANCER; ESTROGEN-INDUCED PROLIFERATION; TRANSGENIC MICE; TGF-ALPHA; MIDDLE-T; FACTOR RECEPTOR; NEOPLASTIC TRANSFORMATION; ONCOGENE EXPRESSION; EPITHELIAL-CELLS; NEU ONCOGENE AB The c-myc oncogene is commonly amplified in breast cancer and is known to interact synergistically with transforming growth factor alpha (TGF alpha) in vitro to promote phenotypic transformation of mammary epithelial cells. In addition, both genes are under sex steroid hormone regulation in breast cancer. We have used a bitransgenic mouse approach to test the relevance of Myc-TGF alpha interaction in mammary gland tumorigenesis of virgin animals in vivo. We mated single transgenic TGF alpha and c-myc mouse strains to yield double transgenic offspring for TGF alpha and c-myc. All (20 of 20) double transgenic TGF alpha/c-myc animals developed synchronous mammary tumors at a mean age of 66 days. An unexpected finding was that tumor latency and frequency in males and virgin females were identical. Thus, two gene products that are known to be coinduced in breast cancer by the sex hormones estrogen and progesterone strongly synergize to induce synchronous mammary tumors, independent of sex. The tumors, despite being estrogen receptor positive, were readily transplanted as highly malignant s.c. cancers in ovariectomized nude mice. Although approximately one-half of single transgenic c-myc virgin females also eventually developed mammary gland tumors, these were stochastic and arose after a long latency period of 9-12 months. Single transgenic virgin TGF alpha females and males, c-myc males, and transgene-negative littermates did not develop tumors (ages up to 15 months). The salivary glands of double transgenic animals also coexpress the two transgenes and show pathological abnormalities ranging from hyperplasias to frank adenocarcinomas. In contrast, the salivary glands of single transgenic and wild-type animals showed only mild hyperplasias or metaplasias, but tumors were not observed. In situ hybridization analysis of mammary and salivary glands revealed that hyperplastic and tumorous areas colocalize with regions that overexpress both the TGF alpha and c-myc transgenes. This indicates that there is a requirement for the presence of both proteins for transformation of these glands. In summary, TGF alpha and c-Myc synergize in an extremely powerful way to cause breast and salivary gland tumorigenesis in males and virgin females without a requirement for pregnancies. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC 20007. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Amundadottir, Laufey/L-7656-2016 OI Amundadottir, Laufey/0000-0003-1859-8971 NR 53 TC 78 Z9 79 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1995 VL 6 IS 6 BP 737 EP 748 PG 12 WC Cell Biology SC Cell Biology GA RC828 UT WOS:A1995RC82800014 PM 7669729 ER PT J AU KAMP, TJ MITAS, M FIELDS, KL ASOH, S CHIN, HM MARBAN, E NIRENBERG, M AF KAMP, TJ MITAS, M FIELDS, KL ASOH, S CHIN, HM MARBAN, E NIRENBERG, M TI TRANSCRIPTIONAL REGULATION OF THE NEURONAL L-TYPE CALCIUM-CHANNEL ALPHA(1D) SUBUNIT GENE SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE CALCIUM CHANNELS; NG108-15 CELLS; MOLECULAR CLONING; TRANSCRIPTION; GENE EXPRESSION REGULATION; ENHANCER ELEMENT; TRINUCLEOTIDE REPEAT; METAL RESPONSE ELEMENT ID METAL RESPONSE ELEMENT; FUNCTIONAL EXPRESSION; SKELETAL-MUSCLE; METALLOTHIONEIN-I; DIHYDROPYRIDINE RECEPTOR; COMPLEMENTARY-DNA; VERTEBRATE CELLS; ALPHA-1 SUBUNIT; MESSENGER-RNAS; NUCLEAR FACTOR AB 1. The transcriptional regulation of the rat brain L-type calcium channel alpha(1D) subunit (RB alpha(1D)) gene was investigated using NG108-15 neuroblastoma-glioma cells. 2. Differentiation of NG108-15 cells in the presence of prostaglandin E(1) or retinoic acid resulted in the appearance of mRNA encoding the RB alpha(1D) subunit detected using Northern blot analysis. 3. A rat genomic DNA library was screened, and a 15.2-kb clone was isolated and partially sequenced which included part of the 5' upstream sequence through the initial part of intron 2 of the RB alpha(1D) gene. 4. Deletion analysis, using a CAT reporter gene and transfected NG108-15 cells, revealed that the 1.2-kb 5'-upstream sequence from the RB alpha(1D) gene contains cis-acting positive and negative regulatory elements. A deletion of the 3' end of exon 1 also suggested the presence of regulatory elements in the first exon. 5. DNase footprinting of exon 1 of the RB alpha(1D) gene revealed two regions protected from digestion by specific protein binding, and the second region included an (ATG)(7) trinucleotide repeat sequence. Electrophoretic mobility shift assays confirmed nuclear protein(s) binding to the (ATG)(7) sequence. 6. The (ATG)(7) sequence functions as a enhancer when linked to a thymidine kinase promoter and a CAT reporter gene. 7. These results provide the initial description of the transcriptional regulation of the RB alpha(1D) gene and identify a novel enhancer that consists of an (ATG), trinucleotide repeat sequence. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. OI Kamp, Timothy/0000-0003-2103-7876 NR 58 TC 21 Z9 22 U1 0 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 1995 VL 15 IS 3 BP 307 EP 326 DI 10.1007/BF02089942 PG 20 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA RG827 UT WOS:A1995RG82700002 PM 7553731 ER PT J AU SELBY, DM SINGER, DF ANDERSON, RW COLIGAN, JE LINDERMAN, JJ NAIRN, R AF SELBY, DM SINGER, DF ANDERSON, RW COLIGAN, JE LINDERMAN, JJ NAIRN, R TI ANTIGEN-PRESENTING CELL-LINES INTERNALIZE PEPTIDE ANTIGENS VIA FLUID-PHASE ENDOCYTOSIS SO CELLULAR IMMUNOLOGY LA English DT Article ID CLASS-II REGION; HISTOCOMPATIBILITY MOLECULES; HORSERADISH-PEROXIDASE; IMMUNOGENIC PEPTIDES; PINOCYTOSED FLUID; LYMPHOID-CELLS; T-CELLS; MHC; COMPLEX; MACROPHAGE AB In this report, we present experimental evidence that antigen-presenting cell lines take up peptide antigens in a manner consistent with fluid-phase endocytosis. Using the fluid phase endocytic marker inulin and a mathematical model for fluid phase uptake, we have found a basal uptake rate constant of approximately 0.9-2 mu m(3)/cell minutes in A20, TA3, and J774 cells. An influenza virus peptide, PB2(303-313), the octapeptide, angiotensin II, an ovalbumin peptide, OVA(323-339), and a guinea pig myelin basic protein peptide, MBP(72-86), have uptake rate constants comparable to inulin, i.e., between 1 and 4 mu m(3)/cell minutes in A20 cells. However, another influenza virus peptide, PB2(146-159), has an uptake rate constant approximately sixfold higher than that found for inulin in A20 cells. We have also determined that the peptide antigens we tested are retained in A20 cells similarly to inulin, with half-times calculated to be from 2 to 13 min as compared to 2 min for inulin. Notably, these results were obtained over short incubation times (up to 20 min) and under conditions that restrict peptide proteolysis and also protein synthesis. We conclude from these studies that peptide antigens enter antigen-presenting cells via fluid-phase endocytosis. (C) 1995 Academic Press, Inc. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT CHEM ENGN,ANN ARBOR,MI 48109. NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [P30CA46592]; NIAMS NIH HHS [P60AR20557]; PHS HHS [A119273] NR 38 TC 7 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1995 VL 163 IS 1 BP 47 EP 54 DI 10.1006/cimm.1995.1097 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RA299 UT WOS:A1995RA29900006 PM 7538910 ER PT J AU YU, XL HATHOUT, Y FENSELAU, C SOWDER, RC HENDERSON, LE RICE, WG MENDELEYEV, J KUN, E AF YU, XL HATHOUT, Y FENSELAU, C SOWDER, RC HENDERSON, LE RICE, WG MENDELEYEV, J KUN, E TI SPECIFIC DISULFIDE FORMATION IN THE OXIDATION OF HIV-1 ZINC-FINGER PROTEIN NUCLEOCAPSID P7 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOLUTION-STATE STRUCTURE; TYPE-1; BINDING; 3-NITROSOBENZAMIDE; RETROVIRUSES; INFECTIVITY; INHIBITION; SEQUENCES; SITE AB In vitro oxidation of the HIV-1 nucleocapsid protein p7 by the C-nitroso compound 3-nitrosobenzamide (NOBA) has been investigated. When reconstituted p7 was incubated with NOBA, three disulfide bonds mere formed per molecule of p7, Cys 15-Cys 18, Cys 28-Cys 36, and Cys 39-Cys 49. These were identified using the proteolytic enzyme endoproteinase Lys-C and mass spectrometry. When the denatured protein (Apo-p7) was incubated with NOBA, a more random pattern of multiple S-S Linkages was found. Oxidation of reconstituted p7 also occurred on treatment with cupric ions (CU2+) and the same three major disulfide bonds were formed as in the reaction with NOBA. These results suggest the interpretation that the oxidation reaction occurs at the zinc-binding centers while zinc cations are still bound and that the two zinc fingers are not identical in their chemical properties. This latter point is consistent with the independent biological roles reported previously for the two fingers in the viral infection cycle. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,AIDS VACCINE PROGRA,FREDERICK,MD 21702. SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,OCTAMER RES FDN,ENVIRONM TOXICOL & CHEM LAB,TIBURON,CA 94920. RP YU, XL (reprint author), UNIV MARYLAND,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228, USA. FU NCI NIH HHS [1-CO-74102]; NIGMS NIH HHS [GM-21248] NR 22 TC 33 Z9 34 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUN PY 1995 VL 8 IS 4 BP 586 EP 590 DI 10.1021/tx00046a013 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA RC056 UT WOS:A1995RC05600014 PM 7548739 ER PT J AU JOHNSON, BE AF JOHNSON, BE TI BIOLOGIC AND MOLECULAR PROGNOSTIC FACTORS - IMPACT ON TREATMENT OF PATIENTS WITH NONSMALL CELL LUNG-CANCER SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID GROWTH-FACTOR-RECEPTOR; RAS GENE-MUTATIONS; FACTOR-ALPHA; AUTOCRINE SECRETION; SHORTENED SURVIVAL; ADENOCARCINOMA; EXPRESSION; CHEMOTHERAPY; PRECURSOR; ONCOGENE AB A wide range of genetic and phenotypic abnormalities have been identified in lung cancer. However, only a few are known to have an impact on patient outcome and thus may influence choice of therapy. Biologic and molecular factors known in this regard include the epidermal growth factor family and its receptors, markers of neuroendocrine differentiation in non-small cell lung cancer, and mutations of the ras gene family. None of these factors, however, dan be considered a standard for selection of patients for therapy until additional information is gleaned from ongoing prospective studies. RP JOHNSON, BE (reprint author), NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,LUNG CANC BIOL SECT,BETHESDA,MD 20892, USA. NR 26 TC 19 Z9 19 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S287 EP S290 DI 10.1378/chest.107.6_Supplement.287S PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100014 PM 7781407 ER PT J AU MULSHINE, JL SCOTT, F AF MULSHINE, JL SCOTT, F TI MOLECULAR MARKERS IN EARLY CANCER-DETECTION - NEW SCREENING TOOLS SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID LUNG-CANCER; CELLS AB Better early detection strategies for lung cancer are clearly needed, About 20 years ago, cytomorphologic criteria were developed for use in staging bronchial epithelium carcinoma. Yet, when sputum cytology was added to chest radiograph in the largest early-screening-of-lung-cancer study carried out to date, the three-arm trial sponsored by the National Cancer Institute, no major outcome benefit was shown, Sputum samples of participants in one of these trials, the Johns Hopkins Lung Project, have been archived. Currently, sputum immunostaining using two monoclonal antibodies directed at a difucosylated Lewis X epitope and a 31-kilodalton protein show correlation between positive staining of these samples and eventual development of lung cancer in the sampled population. Strategics to neutralize the stimulation of growth factors like gastrin-releasing peptide, which are seen in small-cell disease, are also being explored, Development of an epithelial-directed diagnostic test is the most important goal in obtaining early detection tools for lung cancer. Several new tests await prospective trials to evaluate their utility. In developing an early detection test for lung cancer, due to the chronic nature of the risk and the vast at-risk population, cost and patient compliance are two major concerns. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,BETHESDA,MD 20892. NR 20 TC 23 Z9 23 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S280 EP S286 DI 10.1378/chest.107.6_Supplement.280S PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100013 PM 7781406 ER PT J AU LEVY, D LARSON, MG KANNAM, JP AF LEVY, D LARSON, MG KANNAM, JP TI ASSOCIATION OF HEIGHT AND RISK OF MYOCARDIAL-INFARCTION IN WOMEN - RESPONSE SO CIRCULATION LA English DT Letter C1 NHLBI,BETHESDA,MD 20892. BOSTON UNIV,BOSTON,MA 02215. BETH ISRAEL HOSP,BOSTON,MA 02215. RP LEVY, D (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701, USA. NR 1 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 JUN 1 PY 1995 VL 91 IS 11 BP 2853 EP 2854 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RA285 UT WOS:A1995RA28500029 ER PT J AU OHANLON, TP MESSERSMITH, WA DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP MESSERSMITH, WA DALAKAS, MC PLOTZ, PH MILLER, FW TI GAMMA-DELTA T-CELL RECEPTOR GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES IN THE IDIOPATHIC INFLAMMATORY MYOPATHIES SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE GAMMA-DELTA T CELLS; MYOSITIS; T CELL RECEPTORS ID MYOSITIS-SPECIFIC AUTOANTIBODIES; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; RHEUMATOID-ARTHRITIS; CLONAL EXPANSION; GRAVES-DISEASE; SYNOVIAL-FLUID; BRAIN-LESIONS; REPERTOIRE; POLYMYOSITIS AB Autoreactive alpha beta T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). gamma delta T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of gamma delta T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate gamma delta T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). gamma delta TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. gamma delta TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the V gamma 3 and V delta 1 transcripts, whose expression was prominent among gamma delta positive patients. DNA sequence analysis of V gamma 3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the V gamma 3-N-J gamma junctional domain. No amino acid sequence similarities were evident within the V delta-N-D delta-N-J delta region of V delta 1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike alpha beta T cells, gamma delta T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of gamma delta TCR gene expression detected among these patients implies that gamma delta T cell infiltration, when it occurs, is a secondary event perhaps resulting from non-specific inflammatory processes. C1 NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,NIH 29B,ROOM 2G11,HFM-521,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 58 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 1995 VL 100 IS 3 BP 519 EP 528 PG 10 WC Immunology SC Immunology GA RB163 UT WOS:A1995RB16300024 PM 7774065 ER PT J AU Takahashi, N Sausville, EA Breitman, TR AF Takahashi, N Sausville, EA Breitman, TR TI N-(4-hydroxyphenyl)retinamide (Fenretinide) in combination with retinoic acid enhances differentiation and retinoylation of proteins SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; BREAST-CANCER PATIENTS; CELL-LINE HL-60; BINDING-PROTEIN; CRABP-I; TERATOCARCINOMA CELLS; 13-CIS-RETINOIC ACID; HUMAN-PLASMA; VITAMIN-A; EXPRESSION AB The synthetic retinoid, N-(4-hydroxyphenyl)retinamide (4-HPR; Fenretinide), is a cancer chemopreventive and antiproliferative agent whose mechanism of action is unknown, 4-HPR alone is a poor inducer of differentiation of HL-60 cells compared to all-trans-retinoic acid (RA). Here, we found that combinations of 4-HPR and RA synergistically induced differentiation of HL-60 cells, In addition, 4-HPR increased the level of retinoylation, the covalent binding of RA to proteins, Retinoylation occurs in many eukaryotic cell lines and may be involved in RA-induced differentiation. These results suggest that 4-HPR may be a member of a class of retinoids that are active because they displace RA from extracellular and intracellular sites or because they inhibit RA catabolism. On the basis of these proposed mechanisms, retinoids that do not cause differentiation as sole agents may have utility in the clinic in combination with RA. RP Takahashi, N (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892, USA. NR 52 TC 34 Z9 34 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1995 VL 1 IS 6 BP 637 EP 642 PG 6 WC Oncology SC Oncology GA TL081 UT WOS:A1995TL08100009 PM 9816026 ER PT J AU AGAM, G SHIMON, H SOBOLEV, E BELMAKER, RH KLEINMAN, J AF AGAM, G SHIMON, H SOBOLEV, E BELMAKER, RH KLEINMAN, J TI INOSITOL AND INOSITOL MONOPHOSPHATASE IN POSTMORTEM BRAIN FROM MANIC-DEPRESSIVE PATIENTS AND SUICIDES VS CONTROLS SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,BEER SHEVA,ISRAEL. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S166 EP S166 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400585 ER PT J AU CECCO, SA REHAK, NN ELIN, RJ HRISTOVA, EN NIEMELA, JE AF CECCO, SA REHAK, NN ELIN, RJ HRISTOVA, EN NIEMELA, JE TI EFFECT OF PH ON THE CONCENTRATION OF IONIZED MAGNESIUM AND CALCIUM IN CEREBROSPINAL-FLUID SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S157 EP S157 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400545 ER PT J AU CECCO, SA REHAK, NN ELIN, RJ GEORGE, DT HRISTOVA, EN NIEMELA, JE AF CECCO, SA REHAK, NN ELIN, RJ GEORGE, DT HRISTOVA, EN NIEMELA, JE TI EFFECT OF LACTATE CONCENTRATION ON RESULTS FOR IONIZED MAGNESIUM AND CALCIUM SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S156 EP S157 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400544 ER PT J AU CHESLER, R COSTELLO, R CSAKO, G AF CHESLER, R COSTELLO, R CSAKO, G TI EVALUATION OF A DIRECT LDL-CHOLESTEROL (LDL-C) ASSAY SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S141 EP S141 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400477 ER PT J AU COSTELLO, R CHESLER, R CSAKO, G AF COSTELLO, R CHESLER, R CSAKO, G TI ASSESSMENT OF AN ELECTROPHORETIC METHOD FOR THE QUANTITATIVE-DETERMINATION OF CHOLESTEROL AND CHOLESTEROL ESTERS IN PLASMA-LIPOPROTEINS SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S143 EP S143 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400485 ER PT J AU CSAKO, G RASHIDIAN, A SHOOBRIDGE, R COSTELLO, R CHESLER, R AF CSAKO, G RASHIDIAN, A SHOOBRIDGE, R COSTELLO, R CHESLER, R TI URINARY LIGHT-CHAIN LADDER PATTERN IN HEALTH AND DISEASE SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S154 EP S154 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400534 ER PT J AU ELIN, RJ RYSCHON, TW ROSENSTEIN, DL RUBINOW, DR NIEMELA, JE BALABAN, RS AF ELIN, RJ RYSCHON, TW ROSENSTEIN, DL RUBINOW, DR NIEMELA, JE BALABAN, RS TI RELATIONSHIP BETWEEN SKELETAL-MUSCLE INTRACELLULAR IONIZED MAGNESIUM AND TOTAL MAGNESIUM OF BLOOD COMPONENTS SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S156 EP S156 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400540 ER PT J AU ELIN, RJ ROSENSTEIN, DL RYSCHON, TW NIEMELA, JE BALABAN, RS RUBINOW, DR AF ELIN, RJ ROSENSTEIN, DL RYSCHON, TW NIEMELA, JE BALABAN, RS RUBINOW, DR TI SKELETAL-MUSCLE INTRACELLULAR IONIZED MAGNESIUM AND TOTAL MAGNESIUM OF BLOOD-CONSTITUENTS DETERMINED ACROSS THE MENSTRUAL-CYCLE SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S155 EP S155 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400537 ER PT J AU HRUSZKEWYCZ, AM DELGADO, RM BENNETT, WP WELSH, JA VAHAKANGAS, KH WEINTRAUB, BD GRACE, MB AF HRUSZKEWYCZ, AM DELGADO, RM BENNETT, WP WELSH, JA VAHAKANGAS, KH WEINTRAUB, BD GRACE, MB TI EVALUATION OF COLD SSCP USING PRECAST MIDI-GELS FOR MUTATION DETECTION IN THE P53 TUMOR-SUPPRESSOR GENE AND THE THYROID-HORMONE RECEPTOR-BETA GENE SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NIH,DEPT CLIN PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892. NCI,DEPT HUMAN CARCINOGENESIS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S107 EP S107 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400328 ER PT J AU NAGY, B COSTELLO, R YARBORO, C PUCINO, F SCOTT, D EGGERMAN, T KLIPPEL, JH BALOW, J CSAKO, G AF NAGY, B COSTELLO, R YARBORO, C PUCINO, F SCOTT, D EGGERMAN, T KLIPPEL, JH BALOW, J CSAKO, G TI APOLIPOPROTEIN(A) (APO[A]) SIZE POLYMORPHISM AND LIPOPROTEIN(A) (LP[A]) CONCENTRATION IN WHITE AND BLACK HEALTHY-SUBJECTS AND PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Nagy, Balint/F-6943-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S141 EP S141 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400478 ER PT J AU REHAK, NN CECCO, SA ELIN, RJ HRISTOVA, EN NIEMELA, JE AF REHAK, NN CECCO, SA ELIN, RJ HRISTOVA, EN NIEMELA, JE TI LINEARITY OF THE AVL AND NOVA MAGNESIUM AND CALCIUM-ION SELECTIVE ELECTRODES SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S173 EP S173 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400617 ER PT J AU REMALEY, AT BREWER, HB HOEG, JM AF REMALEY, AT BREWER, HB HOEG, JM TI ISOLATION OF NOVEL DIETARY-CHOLESTEROL REGULATED GENES FROM A PCR-BASED SUBTRACTION LIBRARY OF RABBIT LIVER SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S139 EP S139 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400467 ER PT J AU SAMPSON, M RUDDEL, M HENDRICKS, C TAYLOR, S ELIN, RJ AF SAMPSON, M RUDDEL, M HENDRICKS, C TAYLOR, S ELIN, RJ TI 3 METHODS FOR DETERMINATION OF INSULIN COMPARED SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1995 VL 41 IS 6 SU S BP S39 EP S39 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400028 ER PT J AU BALIAN, JD SUKHOVA, N HARRIS, JW HEWETT, J PICKLE, L GOLDSTEIN, JA WOOSLEY, RL FLOCKHART, DA AF BALIAN, JD SUKHOVA, N HARRIS, JW HEWETT, J PICKLE, L GOLDSTEIN, JA WOOSLEY, RL FLOCKHART, DA TI THE HYDROXYLATION OF OMEPRAZOLE CORRELATES WITH S-MEPHENYTOIN METABOLISM - A POPULATION STUDY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENETIC-POLYMORPHISM; DRUG-METABOLISM; BLADDER-CANCER; OXIDATION; DEBRISOQUIN; CAUCASIANS; RATIO AB We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism, Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers, Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection, Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing, All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance, Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r(2) = 0.681; P < 0.001), Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. NIEHS,RES TRIANGLE PK,NC 27709. RI Goldstein, Joyce/A-6681-2012 FU NIGMS NIH HHS [T32-GM 08386] NR 38 TC 135 Z9 141 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1995 VL 57 IS 6 BP 662 EP 669 DI 10.1016/0009-9236(95)90229-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RE818 UT WOS:A1995RE81800008 PM 7781266 ER PT J AU SCHMIDT, ME MATOCHIK, JA RISINGER, RC SCHOUTEN, JL ZAMETKIN, AJ COHEN, RM POTTER, WZ AF SCHMIDT, ME MATOCHIK, JA RISINGER, RC SCHOUTEN, JL ZAMETKIN, AJ COHEN, RM POTTER, WZ TI REGIONAL BRAIN GLUCOSE-METABOLISM AFTER ACUTE ALPHA(2)-BLOCKADE BY IDAZOXAN SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; POSTMORTEM HUMAN-BRAIN; CEREBRAL BLOOD-FLOW; LOCUS COERULEUS; ENDOGENOUS NORADRENALINE; RAT HIPPOCAMPUS; ALPHA-2 ADRENOCEPTORS; NUCLEUS-ACCUMBENS; PANIC DISORDER; BINDING-SITES AB Background: Several classes of antidepressant drugs act on alpha(2)-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha(2)-binding and in vivo responses mediated by alpha(2)-receptors. Measurement of regional brain metabolic response to an alpha(2)-antagonist may be a useful method for further definition of the role alpha(2)-receptor regulation plays in the treatment of neuropsychiatric disorders. Methods: Regional brain glucose metabolism was measured before and after infusion with 200 mu g/kg idazoxan with use of F-18-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured. Results: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response. Conclusions: Our findings are consistent with regionally specific effects of alpha(2)-blockade. This method may be useful for the study of alpha(2)-receptor function in humans. C1 NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. RP SCHMIDT, ME (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,ROOM 2D46,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 61 TC 13 Z9 14 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1995 VL 57 IS 6 BP 684 EP 695 DI 10.1016/0009-9236(95)90232-5 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RE818 UT WOS:A1995RE81800011 PM 7781269 ER PT J AU GOMEZ, R GHEZZI, F ROMERO, R MUNOZ, H TOLOSA, JE ROJAS, I AF GOMEZ, R GHEZZI, F ROMERO, R MUNOZ, H TOLOSA, JE ROJAS, I TI PREMATURE LABOR AND INTRAAMNIOTIC INFECTION - CLINICAL ASPECTS AND ROLE OF THE CYTOKINES IN DIAGNOSIS AND PATHOPHYSIOLOGY SO CLINICS IN PERINATOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; LOW-BIRTH-WEIGHT; FLUID GLUCOSE-CONCENTRATION; BLOOD-CELL COUNT; TRANSFORMING GROWTH-FACTOR; ENDOTOXIN-INDUCED ABORTION; COLONY-STIMULATING FACTOR AB The role of infection in the pathogenesis of preterm labor and delivery, and the specific mechanisms through which this association is demonstrated are presented. Cellular and biochemical changes that initiate parturition in the setting of infection are discussed, particularly prostaglandins and cytokines. C1 NICHHD,DIV INTRAMURAL,PERINATOL RES BRANCH,WASHINGTON,DC 20007. UNIV CHILE,DEPT OBSTET & GYNECOL,SANTIAGO,CHILE. SOTERO DEL RIO HOSP,SANTIAGO,CHILE. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 307 TC 247 Z9 250 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD JUN PY 1995 VL 22 IS 2 BP 281 EP 342 PG 62 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA RE583 UT WOS:A1995RE58300005 PM 7671540 ER PT J AU HAMA, N BOUMPAS, DT AF HAMA, N BOUMPAS, DT TI CEREBRAL LUPUS-ERYTHEMATOSUS - DIAGNOSIS AND RATIONAL DRUG-TREATMENT SO CNS DRUGS LA English DT Article ID DOSE INTRAVENOUS IMMUNOGLOBULIN; SEVERE NEUROPSYCHIATRIC LUPUS; ACUTE NONLYMPHOCYTIC LEUKEMIA; TRANSVERSE MYELITIS; PULSE CYCLOPHOSPHAMIDE; COGNITIVE IMPAIRMENT; ANTIBODIES; THERAPY; ASSOCIATION; METHYLPREDNISOLONE AB Neuropsychiatric symptoms are common in patients with systemic lupus erythematosus (SLE) and can be separated into primary events [neuropsychiatric lupus (NL)] resulting directly from immune-mediated injury to the CNS and secondary events resulting from disease in other organs and/or complications of therapy. A vigorous search for secondary causes (especially infections) and documentation of the extent and nature of the underlying process are crucial in managing patients, Control of the acute neuropsychiatric manifestations with neuroactive drugs and suppression of the underlying pathogenetic mechanisms with anti-inflammatory and/or immunosuppressive drugs or anticoagulants are the main goals of therapy. RP HAMA, N (reprint author), NIDDK,KIDNEY DIS SECT,BLDG 10,ROOM 3N112,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 3 Z9 3 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD JUN PY 1995 VL 3 IS 6 BP 416 EP 426 DI 10.2165/00023210-199503060-00002 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RC054 UT WOS:A1995RC05400002 ER PT J AU MIRONOV, AA ALEXANDROV, NN BOGODAROVA, NY GRIGORJEV, A LEBEDEV, VF LUNOVSKAYA, LV TRUCHAN, ME PEVZNER, PA AF MIRONOV, AA ALEXANDROV, NN BOGODAROVA, NY GRIGORJEV, A LEBEDEV, VF LUNOVSKAYA, LV TRUCHAN, ME PEVZNER, PA TI DNASUN - A PACKAGE OF COMPUTER-PROGRAMS FOR THE BIOTECHNOLOGY LABORATORY SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Note ID MULTIPLE ALIGNMENT; SEQUENCE; SEARCH AB The paper describes a new software package DNASUN developed for supporting gene engineering laboratories. package provides a user-friendly interface for experimental researches and supports the traditional nucleotide/protein sequence analysis as well as physical mapping, sequencing, plasmid manipulations, optimal oligonucleotide probe selection and other common molecular biology procedures. C1 NCI,FREDERICK,MD 21702. IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. PENN STATE UNIV,DEPT COMP SCI & ENGN,UNIVERSITY PK,PA 16802. RP MIRONOV, AA (reprint author), NIIGENETIKA,NATL BIOTECHNOL CTR,MATH METHODS LAB,MOSCOW 113545,RUSSIA. RI Mironov, Andrey/C-8024-2012 FU NHGRI NIH HHS [1 R01 HG00987-01] NR 23 TC 5 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUN PY 1995 VL 11 IS 3 BP 331 EP 335 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA RK610 UT WOS:A1995RK61000014 PM 7583703 ER PT J AU FEIGL, P BLUMENSTEIN, B THOMPSON, I CROWLEY, J WOLF, M KRAMER, BS COLTMAN, CA BRAWLEY, OW FORD, LG AF FEIGL, P BLUMENSTEIN, B THOMPSON, I CROWLEY, J WOLF, M KRAMER, BS COLTMAN, CA BRAWLEY, OW FORD, LG TI DESIGN OF THE PROSTATE-CANCER PREVENTION TRIAL (PCPT) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE CHEMOPREVENTION; PROSTATE CANCER; MONITORING TECHNIQUES; BIASED ASCERTAINMENT ID DIGITAL RECTAL EXAMINATION; ANTIGEN; MEN; HYPERPLASIA; FINASTERIDE; MANAGEMENT; OUTCOMES; WHITE AB The PCPT is a chemoprevention trial of finasteride with a primary endpoint of biopsy-proven presence or absence of prostate cancer. A total of 18,000 healthy men, aged 55 years and older, will be randomized. Half will receive finasteride (5 mg/day) and half will receive placebo (one matching tablet per day) for 7 years. The trial is designed to have 92% power to detect a 25% reduction in period prevalence of biopsy-proven disease using a two-sided test with alpha = 0.05. The trial is complicated by the known impact of finasteride on the major screening test for prostate cancer, prostate specific antigen (PSA). This paper describes the PCPT design with reference to alternatives that were considered. The chosen design depends on five critical assumptions that must be monitored closely throughout the 9-year trial. C1 BROOKE ARMY MED CTR,DEPT SURG,UROL SERV,FT SAM HOUSTON,TX 78234. NATL CANC INST,DIV CANC PREVENT & CONTROL,BETHESDA,MD. SW ONCOL GRP,OPERAT OFF,SAN ANTONIO,TX. SAN ANTONIO CANC INST,SAN ANTONIO,TX. RP FEIGL, P (reprint author), FRED HUTCHINSON CANC RES CTR,CTR STAT,SW ONCOL GRP,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. FU NCI NIH HHS [2 U10 CA37429-09, 5 U10 CA37429] NR 32 TC 106 Z9 107 U1 1 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1995 VL 16 IS 3 BP 150 EP 163 DI 10.1016/0197-2456(94)00XXX-M PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QR790 UT WOS:A1995QR79000003 PM 7540965 ER PT J AU KELLY, K SIEBENLIST, U AF KELLY, K SIEBENLIST, U TI IMMEDIATE-EARLY GENES INDUCED BY ANTIGEN RECEPTOR STIMULATION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID ZINC-FINGER GENE; KAPPA-B; T-CELLS; PROTEIN; ACTIVATION; GROWTH; KINASE; TRANSCRIPTION; PHOSPHATASE; EXPRESSION AB Immediate early genes induced by triggering of the TCR frequently encode proteins that act in signal transduction cascades. Recent advances concerning several immediate-early proteins have been made, including signal-induced regulation of NF-kappa B by I kappa-B, the role of Nur77 in T-cell selection and apoptosis, and the function of PAC-1 in regulating the Ras/ERK pathway. C1 NIH,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP KELLY, K (reprint author), NIH,PATHOL LAB,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892, USA. NR 45 TC 42 Z9 42 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1995 VL 7 IS 3 BP 327 EP 332 DI 10.1016/0952-7915(95)80106-5 PG 6 WC Immunology SC Immunology GA RK656 UT WOS:A1995RK65600005 PM 7546396 ER PT J AU REINER, SL SEDER, RA AF REINER, SL SEDER, RA TI T-HELPER CELL-DIFFERENTIATION IN IMMUNE-RESPONSE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CUTANEOUS LEISHMANIASIS; INTERFERON-GAMMA; EXPRESSION; PROFILES; SUBSETS; MICE; INTERLEUKIN-4; MACROPHAGES; RESOLUTION AB Significant progress has been made in understanding the maturation of antigen-specific CD4(+) T helper cell responses. Recent progress centers on the network of cytokines, accessory molecules, and cell types that shapes the differentiation of distinct T helper cell subsets. Use of transgenic and knockout mice and well characterized in vivo models have helped clarify the interdependence or independence of many of these complex factors. C1 UNIV CHICAGO,COMM IMMUNOL,CHICAGO,IL 60637. NIAID,LYMPHOKINE REGULAT UNIT,BETHESDA,MD 20892. RP REINER, SL (reprint author), UNIV CHICAGO,GWENN KNAPP CTR LUPUS & IMMUNOL RES,DEPT MED,924 E 57TH ST,CHICAGO,IL 60637, USA. FU NIAID NIH HHS [AI01309] NR 65 TC 84 Z9 89 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1995 VL 7 IS 3 BP 360 EP 366 DI 10.1016/0952-7915(95)80111-1 PG 7 WC Immunology SC Immunology GA RK656 UT WOS:A1995RK65600010 PM 7546401 ER PT J AU DOHERTY, TM AF DOHERTY, TM TI T-CELL REGULATION OF MACROPHAGE FUNCTION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MIGRATION-INHIBITORY FACTOR; IFN-GAMMA; CYTOKINE PRODUCTION; IL-10; INTERLEUKIN-10; ACTIVATION; MODULATION; MICE; TH1; LYMPHOCYTES AB Macrophage function has long been known to be controlled by activated T cells. As the cytokines that control macrophage activation are defined, it is becoming apparent that macrophage 'activation' is more subtle than previously appreciated. Moreover, recent work has shown the dependence of T-cell development on macrophages, from the costimulation of T cells by macrophage surface molecules such as the B7 family, to the modulation by monokines of T-cell phenotype and growth, including IL-7, IL-10, IL-12 and IL-15. Combinations of cytokines and costimulators have revealed some of the processes by which an apparently dichotomous T-cell response can regulate the subtle diversity of the immune response. RP DOHERTY, TM (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,BETHESDA,MD 20892, USA. NR 43 TC 62 Z9 65 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1995 VL 7 IS 3 BP 400 EP 404 PG 5 WC Immunology SC Immunology GA RK656 UT WOS:A1995RK65600016 PM 7546407 ER PT J AU DANI, JA MAYER, ML AF DANI, JA MAYER, ML TI STRUCTURE AND FUNCTION OF GLUTAMATE AND NICOTINIC ACETYLCHOLINE-RECEPTORS SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GATED ION CHANNELS; ALPHA-SUBUNIT; DELTA-SUBUNIT; CENTRAL NEURONS; BINDING-SITES; CALCIUM PERMEABILITY; DIVALENT-CATIONS; AMINO-ACIDS; PERMEATION AB The past year has seen remarkable progress in defining the structure of Various ligand-gated ion channels. Images of opened and closed nicotinic acetylcholine receptors at 9 Angstrom resolution have now made it easier to identify the conformational changes underlying gating. In addition, recent studies on glutamate receptors have led to a radical revision of their postulated transmembrane topology: models for agonist-binding and allosteric domains now use sites previously thought to lie in cytoplasmic loops. Other areas that are being actively pursued include identification of the amino acids lining the ion channels, accurate measurements of Ca2+ fIuxes, and tests of transmembrane topology in kainate receptor subunits. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. RP DANI, JA (reprint author), BAYLOR COLL MED,DIV NEUROSCI,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. RI Mayer, Mark/H-5500-2013 FU NINDS NIH HHS [NS21229] NR 81 TC 51 Z9 51 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 1995 VL 5 IS 3 BP 310 EP 317 DI 10.1016/0959-4388(95)80043-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RH129 UT WOS:A1995RH12900007 PM 7580153 ER PT J AU LICHT, T LUBBERT, M MARTENS, C BROSS, KJ FIEBIG, HH MERTELSMANN, R HERRMANN, F AF LICHT, T LUBBERT, M MARTENS, C BROSS, KJ FIEBIG, HH MERTELSMANN, R HERRMANN, F TI MODULATION OF VINDESINE AND DOXORUBICIN RESISTANCE IN MULTIDRUG-RESISTANT PLEURAL MESOTHELIOMA CELLS BY TUMOR-NECROSIS-FACTOR-ALPHA SO CYTOKINES AND MOLECULAR THERAPY LA English DT Article DE CHEMOTHERAPY; CHEMOSENSITIZING AGENTS; CYTOKINES; MDR1 GENE; P-GLYCOPROTEIN ID DRUG-RESISTANCE; P-GLYCOPROTEIN; BONE-MARROW; CHEMOTHERAPY; LEUKEMIA; ACCUMULATION; TRANSPORTER; EXPRESSION; VERAPAMIL; TOXICITY AB Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the cytotoxicity of a variety of antineoplastic agents. To examine whether multidrug-resistant cells are targets of TNF-alpha, and whether TNF-alpha is capable of modulating chemoresistance of these cells, a pleural mesothelioma cell line (PXF1118L) and two multidrug-resistant sublines thereof were used as experimental models. Drug resistance of these cells was due to P-glycoprotein expression, as confirmed by (1) staining with a monoclonal antibody (MRK16) specific for human P-glycoprotein, (2) decreased accumulation of [H-3]vinblastine that was reversed by verapamil, and (3) enhanced cytotoxicity of vindesine in the presence of verapamil. Parental and multidrug-resistant cells exhibited little but comparable sensitivity to TNF-alpha alone. Combining TNF-alpha with vindesine or, to a lesser extent, with doxorubicin, but not with cisplatin, resulted in greater cytotoxicity towards multidrug-resistant cells than seen for each compound alone, indicating a synergism. In contrast, TNF-alpha failed to modulate vindesine or doxorubicin cytotoxicity in parental cells. [H-3]Vinblastine accumulation was unaffected by TNF-alpha, and chemoresistance was reduced by TNF-alpha also in the presence of verapamil (10 mu M), indicating that TNF-alpha was acting in a way different from calcium-channel blockers. Though the molecular mechanism by which TNF-alpha was enhancing vindesine and doxorubicin cytotoxicity remained undefined in this study, the numbers of TNF-alpha binding sites on parental and on multidrug-resistant cells were similar, and P-glycoprotein expression was unmodulated during the entire 48 h incubation period. In conclusion, we show that TNF-alpha increases the cytotoxicity of anticancer drugs in multidrug-resistant tumor cells by a mechanism that differs from most chemosensitizing agents, including verapamil. Further studies will be needed to clarify the mechanism by which TNF-alpha synergizes with anticancer drugs. C1 FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,ROBERT ROSSLE CANC CTR,DEPT MED ONCOL & APPL MOLEC BIOL,D-13122 BERLIN,GERMANY. UNIV FREIBURG,DEPT INTERNAL MED HEMATOL ONCOL 1,FREIBURG,GERMANY. NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV REGENSBURG,DEPT INTERNAL MED,W-8400 REGENSBURG,GERMANY. NR 32 TC 9 Z9 9 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1355-6568 J9 CYTOKINES MOL THER JI Cytokines Mol. Ther. PD JUN PY 1995 VL 1 IS 2 BP 123 EP 132 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Research & Experimental Medicine GA TF515 UT WOS:A1995TF51500004 PM 9384669 ER PT J AU MASTELLER, EL LARSEN, RD CARLSON, LM PICKEL, JM NICKOLOFF, B LOWE, J THOMPSON, CB LEE, KP AF MASTELLER, EL LARSEN, RD CARLSON, LM PICKEL, JM NICKOLOFF, B LOWE, J THOMPSON, CB LEE, KP TI CHICKEN B-CELLS UNDERGO DISCRETE DEVELOPMENTAL-CHANGES IN SURFACE CARBOHYDRATE STRUCTURE THAT APPEAR TO PLAY A ROLE IN DIRECTING LYMPHOCYTE MIGRATION DURING EMBRYOGENESIS SO DEVELOPMENT LA English DT Article DE AVIAN B CELL DEVELOPMENT; LYMPHOCYTE MIGRATION; SIALYL LEWIS X; BURSA OF FABRICIUS; CHICK; CARBOHYDRATE ID DIFFERENTIAL REGULATION; EMBRYONIC BURSA; STEM-CELLS; FABRICIUS; GENE; REARRANGEMENT; ONTOGENY; ANTIGEN; RECIRCULATION; EXPRESSION AB The migration of progenitor cells to specific microenvironments is essential for the development of complex organisms. Avian species possess a unique primary lymphoid organ, the bursa of Fabricius, that plays a central role in the development of B cells. B cell progenitors, however, arise outside the bursa of Fabricius and, during embryonic development, must migrate through the vasculature to the bursa of Fabricius. In this report, we demonstrate that these progenitor B cells express the sialyl Lewis x carbohydrate structure previously shown to be a ligand for the selectin family of vascular adhesion receptors. Soon after migration to the bursa of Fabricius, B cell progenitors are induced to undergo a developmental switch and terminate the expression of sialyl Lewis x in a temporal pattern that correlates with the developmental decline in the ability of these cells to home to the bursa of Fabricius upon transplantation. The induction of the developmental switch in the glycosylation pattern of developing B cells requires the bursal environment, In addition, sialyl Lewis x carbohydrate determinants or structurally similar determinants on the surface of immortalized bursal lymphoid stem cells participate in the adherence of these cells to the vascular regions of the bursal microenvironment, These data demonstrate that the carbohydrate structure sialyl Lewis x is developmentally regulated during chicken B cell development and may facilitate the migration of B cell progenitors to the bursal microenvironment by serving as a ligand for a lectin-like adhesion receptor. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOLEC GENET & CELL BIOL,DEPT MED,CHICAGO,IL 60637. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NIAID,BETHESDA,MD 20892. GLYCOMED INC,ALAMEDA,CA 94501. UNIV MICHIGAN,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. FU NCI NIH HHS [R37CA48023] NR 37 TC 32 Z9 32 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1995 VL 121 IS 6 BP 1657 EP 1667 PG 11 WC Developmental Biology SC Developmental Biology GA RD802 UT WOS:A1995RD80200010 PM 7600983 ER PT J AU KNECHT, AK GOOD, PJ DAWID, IB HARLAND, RM AF KNECHT, AK GOOD, PJ DAWID, IB HARLAND, RM TI DORSAL-VENTRAL PATTERNING AND DIFFERENTIATION OF NOGGIN-INDUCED NEURAL TISSUE IN THE ABSENCE OF MESODERM SO DEVELOPMENT LA English DT Article DE NOGGIN; NEURAL INDUCTION; DORSAL-VENTRAL PATTERNING; NEURONAL DIFFERENTIATION; RNA-BINDING PROTEIN; SYNAPTOBREVIN; LIPOCALIN ID XENOPUS-LAEVIS EMBRYOS; NERVOUS-SYSTEM; SPEMANN ORGANIZER; BINDING PROTEIN; ANTEROPOSTERIOR PATTERN; EXPRESSION; INDUCTION; ECTODERM; GENE; AXIS AB In Xenopus development, dorsal mesoderm is thought to play a key role in both induction and patterning of the nervous system, Previously, we identified a secreted factor, noggin, which is expressed in dorsal mesoderm and which can mimic that tissue's neural-inducing activity, without inducing mesoderm, Here the neural tissue induced in ectodermal explants by noggin is further characterized using four neural-specific genes: two putative RNA-binding proteins, nrp-1 and etr-1; the synaptobrevin sybII; and the lipocalin cpl-1. First we determine the expression domain of each gene during embryogenesis, Then we analyze expression of these genes in noggin-treated explants, All markers, including the differentiated marker sybII, are expressed in noggin-induced neural tissue, Furthermore, cpl-1, a marker of dorsal brain, and etr-1, a marker absent in much of the dorsal forebrain, are expressed in non-overlapping territories within these explants, We conclude that the despite the absence of mesoderm, noggin-induced neural tissue shows considerable differentiation and organization, which may represent dorsal-ventral patterning of the forebrain. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 60 TC 190 Z9 192 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1995 VL 121 IS 6 BP 1927 EP 1935 PG 9 WC Developmental Biology SC Developmental Biology GA RD802 UT WOS:A1995RD80200033 PM 7601005 ER PT J AU FINCH, PW CUNHA, GR RUBIN, JS WONG, J RON, D AF FINCH, PW CUNHA, GR RUBIN, JS WONG, J RON, D TI PATTERN OF KERATINOCYTE GROWTH-FACTOR AND KERATINOCYTE GROWTH-FACTOR RECEPTOR EXPRESSION DURING MOUSE FETAL DEVELOPMENT SUGGESTS A ROLE IN MEDIATING MORPHOGENETIC MESENCHYMAL EPITHELIAL INTERACTIONS SO DEVELOPMENTAL DYNAMICS LA English DT Article DE GENE EXPRESSION; IN SITU HYBRIDIZATION; KERATINOCYTE GROWTH FACTOR; MESENCHYMAL-EPITHELIAL INTERACTION; MORPHOGENESIS; ORGANOGENESIS ID SKELETAL-MUSCLE; TOOTH DEVELOPMENT; CLONING SYSTEM; CDNA CLONING; FGF RECEPTOR; DIFFERENTIATION; FAMILY; GENE; MESODERM; EMBRYO AB Mesenchymal cells are required for the induction of epithelial development during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epithelial cells, suggesting that it may play a role in mediating these interactions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGFR) transcripts during organogenesis and limb formation in mouse embryos (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clones were isolated. There was extensive identity between the deduced mouse KGF protein sequence and that of its human and rat cognates, indicating that this gene has been highly conserved during mammalian evolution. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointestinal, and urogenital systems, whose development is dependent upon mesenchymal-epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR. KGF and KGFR mRNA was also expressed in certain other tissues such as perichondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesenchymal-epithelial interactions. KGF expression was also detected in tissues isolated from human embryos, suggesting similar functions for KGF in human development. Taken together, our results suggest that KGF plays an important role in mediating mesenchymal-epithelial interactions during organogenesis, but may also have other developmental functions in tissues not governed by such interactions. (C) 1995 Wiley-Liss, Inc. C1 BROWN UNIV,RHODE ISL HOSP,DEPT CLIN NEUROSCI,PROVIDENCE,RI 02903. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 05388]; NIDDK NIH HHS [DK 32157, DK 47517] NR 52 TC 247 Z9 247 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 1995 VL 203 IS 2 BP 223 EP 240 PG 18 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA RD009 UT WOS:A1995RD00900009 PM 7655084 ER PT J AU NELSON, RG BENNETT, PH AF NELSON, RG BENNETT, PH TI THE DEVELOPMENT AND COURSE OF RENAL-DISEASE AMONG PIMA-INDIANS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS SO DIABETES NUTRITION & METABOLISM LA English DT Review DE DIABETIC NEPHROPATHY; NON-INSULIN DEPENDENT DIABETES; EPIDEMIOLOGY; RISK FACTORS; PATHOPHYSIOLOGY; PIMA INDIANS ID GLOMERULAR-FILTRATION RATE; ALBUMIN EXCRETION; GROSS PROTEINURIA; NEPHROPATHY; ONSET; HEMODYNAMICS; MECHANISMS; MORTALITY; ROCHESTER; MINNESOTA RP NELSON, RG (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. NR 42 TC 4 Z9 4 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-3402 J9 DIABETES NUTR METAB JI Diabetes Nutr. Metab. PD JUN PY 1995 VL 8 IS 3 BP 149 EP 158 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA RR304 UT WOS:A1995RR30400003 ER PT J AU KOZKA, IJ CLARK, AE RECKLESS, JPD CUSHMAN, SW GOULD, GW HOLMAN, GD AF KOZKA, IJ CLARK, AE RECKLESS, JPD CUSHMAN, SW GOULD, GW HOLMAN, GD TI THE EFFECTS OF INSULIN ON THE LEVEL AND ACTIVITY OF THE GLUT4 PRESENT IN HUMAN ADIPOSE-CELLS SO DIABETOLOGIA LA English DT Article DE GLUCOSE TRANSPORT; HUMAN ADIPOCYTES; PHOTOLABELING ID GLUCOSE-TRANSPORT ACTIVITY; KINETIC-PARAMETERS; RAT ADIPOCYTES; 3T3-L1 CELLS; STIMULATED TRANSLOCATION; XENOPUS OOCYTES; ISOFORMS; BASAL AB Human adipose cells are much less responsive to insulin stimulation of glucose transport activity than are rat adipocytes. To assess and characterize this difference, we have determined the rates of 3-O-methyl-D-glucose transport in human adipose cells and have compared these with the levels of glucose transporter 4 (GLUT4) assessed by using the bis-mannose photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos-4-yloxy)-2-propylamine, ATB-BMPA. The rates of 3-O-methyl-D-glucose transport and the cell-surface level of GLUT4 are very similar in the human and rat adipocyte in the basal state. The V-max for 3-O-methyl-D-glucose transport in fully insulin-stimulated human adipose cells is 15-fold lower than in rat adipose cells. Photolabelling of GLUT4 suggests that this low transport activity is associated with a low GLUT4 abundance (39 . 10(4) sites/cell; 19.9 . 10(4) sites at the cell surface). The turnover number for human adipose cell GLUT4 (5.8 . 10(4) min(-1)) is similar to that observed for GLUT4 in rat adipose cells and the mouse cell line, 3T3L1. Since 50% of the GLUT4 is at the cell surface of both human and rat adipose cells in the fully insulin-stimulated state, an inefficient GLUT4 exocytosis process cannot account for the low transport activity. The intracellular retention process appears to have adapted to release, in the basal state, a greater proportion of the total-cellular pool of GLUT4 to the cell surface of the larger human adipocytes. These cell-surface transporters are presumably necessary to provide the basal metabolic needs of the adipocyte. As a consequence of this adaptation to cell size and surface area, the residual intracellular-reserve pool of GLUT4 that is available to respond to insulin is lower in the human than in the rat adipocyte. C1 UNIV BATH,SCH BIOL & BIOCHEM,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. UNIV BATH,ROYAL UNITED HOSP,POSTGRAD MED SCH,BATH BA2 7AY,AVON,ENGLAND. NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. UNIV GLASGOW,DEPT BIOCHEM,GLASGOW G12 8QQ,LANARK,SCOTLAND. NR 25 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1995 VL 38 IS 6 BP 661 EP 666 DI 10.1007/BF00401836 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ605 UT WOS:A1995QZ60500005 PM 7672486 ER PT J AU MUGGEO, M VERLATO, G BONORA, E CIANI, F MOGHETTI, P EASTMAN, R CREPALDI, G DEMARCO, R AF MUGGEO, M VERLATO, G BONORA, E CIANI, F MOGHETTI, P EASTMAN, R CREPALDI, G DEMARCO, R TI LONG-TERM INSTABILITY OF FASTING PLASMA-GLUCOSE PREDICTS MORTALITY IN ELDERLY NIDDM PATIENTS - THE VERONA DIABETES STUDY SO DIABETOLOGIA LA English DT Article DE NON-INSULIN-DEPENDENT DIABETES MELLITUS; MORTALITY; ELDERLY; HYPERGLYCEMIA; GLUCOSE CONTROL ID LIPOPROTEIN COMPOSITION; NONDIABETIC SUBJECTS; RISK-FACTORS; COMPLICATIONS; PREVALENCE; MELLITUS; ABNORMALITIES; TOLERANCE; DISEASE; TRIAL AB The aim of this study was to evaluate whether long-term glucose control, as assessed by fasting plasma glucose determinations during 3 years, is a predictor of all-cause mortality in elderly NIDDM patients. Five hundred and sixty-six NIDDM patients attending the Verona Diabetes Clinic, aged 75 years and over, were followed-up from 1 January 1987 to 31 December 1991 to assess all-cause mortality. From their clinical records all fasting plasma glucose determinations available for the years 1984 to 1986 were collected and analysed. Patients were grouped in tertiles according to mean (M-FPG), coefficient of variation (CV-FPG) and trend over time (slope, S-FPG) of fasting plasma glucose during the period of retrospective evaluation, Mortality was assessed by observed/expected ratios, univariate Kaplan-Meier survival analysis and multivariate Poisson regression model. By 31 December 1991, 61 men and 127 women had died. Increased observed/expected ratios were found in women from the top M-FPG tertile, in patients (men and women) from the top CV-FPG tertile and in patients with a S-FPG less than -0.30 mmol/l per year (lowest tertile). Patients in the lowest tertile of CV-FPG and in the middle tertile of S-FPG had a reduced mortality risk. Kaplan-Meier survival analysis indicated that patients with high CV-FPG as well as those in tertiles I and III of S-FPG (i.e., those with a definitely negative or definitely positive slope) had an increased probability of dying, without any significant differences between the three tertiles of M-FPG. Poisson regression model showed that CV-FPG, but not M-FPG or S-FPG, was an independent significant predictor of mortality, These results suggest that glucose stability needs to be considered along with the absolute level of metabolic control when treating elderly NIDDM patients. C1 UNIV VERONA,DIV METAB DIS,I-37100 VERONA,ITALY. UNIV VERONA,INST MED STAT,I-37100 VERONA,ITALY. NIDDKD,DIV ENDOCRINOL DIABET & METAB DIS,BETHESDA,MD 20892. UNIV PADUA,INST INTERNAL MED,PADUA,ITALY. RI de Marco, Roberto/A-5470-2008; SESM, SESM/C-1440-2008; OI BONORA, Enzo/0000-0003-1074-5164 NR 33 TC 41 Z9 43 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1995 VL 38 IS 6 BP 672 EP 679 DI 10.1007/BF00401838 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ605 UT WOS:A1995QZ60500007 PM 7672488 ER PT J AU SCALA, S SAEKI, T LYNCH, A SALOMON, D MERINO, MJ BATES, SE AF SCALA, S SAEKI, T LYNCH, A SALOMON, D MERINO, MJ BATES, SE TI COEXPRESSION OF TGF-ALPHA, EPIDERMAL GROWTH-FACTOR RECEPTOR, AND P-GLYCOPROTEIN IN NORMAL AND BENIGN DISEASED BREAST TISSUES SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE TGF-ALPHA; EGFR; P-GLYCOPROTEIN; BREAST TISSUE; IMMUNOSTAINING ID PROTEIN-KINASE-C; DRUG ACCUMULATION; CELL-LINE; CANCER; EXPRESSION; RESISTANCE; PHOSPHORYLATION; NEUROBLASTOMA; ADRIAMYCIN; ANTIBODIES AB Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-alpha (TGF alpha), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of the mdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGF alpha staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGF alpha, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 32 TC 13 Z9 13 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD JUN PY 1995 VL 4 IS 2 BP 136 EP 142 DI 10.1097/00019606-199506000-00010 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA QY366 UT WOS:A1995QY36600010 PM 7551294 ER PT J AU SAVAGNER, P KREBSBACH, PH HATANO, O MIYASHITA, T LIEBMAN, J YAMADA, Y AF SAVAGNER, P KREBSBACH, PH HATANO, O MIYASHITA, T LIEBMAN, J YAMADA, Y TI COLLAGEN-II PROMOTER AND ENHANCER INTERACT SYNERGISTICALLY THROUGH SP1 AND DISTINCT NUCLEAR FACTORS SO DNA AND CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; 1ST INTRON; GENE-EXPRESSION; CHAIN ENHANCER; ACTIN PROMOTER; BINDING-SITES; COMMON FACTOR; DNA-BINDING; ACTIVATION; PROTEIN AB The collagen II gene is expressed primarily in chondrocytes. Its transcription is activated through the interaction of cell type-specific regulatory elements located in the promoter region and in the first intron. In this study, we found that a short promoter sequence including two GC boxes was required for efficient enhancer-mediated transcription, Gel-shift analysis, site mutations, and footprint analysis showed that one of the GC boxes bound functionally to an Sp1-related factor and that an oligonucleotide containing this GC box did interact with an enhancer-nuclear factor complex. Additionally, an enhancer-derived oligonucleotide was found to complex CIIZFP, a zinc-finger protein that binds to the enhancer within the first intron and Sp1, but only in presence of CIIZFP. Antibodies against Sp1 specifically inhibited the formation of this complex. Western/Southwestern analysis also showed that a protein complex including Sp1 was able to bind the enhancer and the promoter regions in non-denaturing conditions. This complex was dissociated by denaturation. These results suggest that the formation of a nuclear protein-mediated loop structure between the promoter and enhancer may regulate transcription of the collagen II gene transcription. C1 ECOLE NORMALE SUPER,CNRS,PHYSIOPATHOL DEV LAB,F-75230 PARIS 05,FRANCE. CIBA GEIGY PHARMACEUT CORP,SUMMIT,NJ 07901. RP SAVAGNER, P (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 424,BETHESDA,MD 20892, USA. NR 53 TC 29 Z9 29 U1 0 U2 1 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 JUN PY 1995 VL 14 IS 6 BP 501 EP 510 DI 10.1089/dna.1995.14.501 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA RG132 UT WOS:A1995RG13200005 PM 7598805 ER PT J AU MONTOYA, ID LEVIN, FR FUDALA, PJ GORELICK, DA AF MONTOYA, ID LEVIN, FR FUDALA, PJ GORELICK, DA TI DOUBLE-BLIND COMPARISON OF CARBAMAZEPINE AND PLACEBO FOR TREATMENT OF COCAINE DEPENDENCE SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE COCAINE; DEPENDENCE; CARBAMAZEPINE ID USERS; LIDOCAINE; SEIZURES; DESIGN; DRUGS; RATS AB This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of cocaine dependence. C1 NIDA,INTRAMURAL RES PROGRAM,TREATMENT BRANCH,BALTIMORE,MD 21224. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV MARYLAND,DEPT PSYCHIAT,BALTIMORE,MD. FU Intramural NIH HHS [Z99 DA999999] NR 37 TC 44 Z9 44 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN PY 1995 VL 38 IS 3 BP 213 EP 219 DI 10.1016/0376-8716(95)01101-4 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA RF947 UT WOS:A1995RF94700003 PM 7555621 ER PT J AU BHAGWAT, SV BOYD, MR RAVINDRANATH, V AF BHAGWAT, SV BOYD, MR RAVINDRANATH, V TI RAT-BRAIN CYTOCHROME-P450 - REASSESSMENT OF MONOOXYGENASE ACTIVITIES AND CYTOCHROME-P450 LEVELS SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID O-DEETHYLASE ACTIVITY; OXIDATIVE STRESS; REDUCTASE AB There have been considerable interlaboratory variations in the reported levels of rat brain microsomal cytochrome P450 and associated monooxygenase activities. To ascertain if the variability could be accountable, at least in part, to different methodologies used for microsome preparation, cytochrome P450 monooxygenase components and activities were directly compared herein using brain microsome prepared by various methods. Rat brain microsome isolated using a calcium aggregation method in the presence of dithiothreitol and glycerol contained similar to 100 pmol of cytochrome P450/mg protein. Considerably lower cytochrome P450 levels (e.g. 20-40 pmol/mg protein) were found in brain microsome prepared in a more conventional manner using Tris or phosphate buffers without glycerol and dithiothreitol. The NADPH cytochrome c reductase activity was consistently similar to 23-25 nmol of cytochrome c reduced/min/mg protein, whatever the method of preparation of the brain microsome. Cytochrome P450-associated monooxygenase activities, namely morphine N-demethylase and ethoxycoumarin O-deethylase, were dependent on the amount of protein in the incubation medium, the length of incubation, and the ratio of the concentration of the substrate to the amount of protein in the incubation mixture. The specific activity of morphine N-demethylase was constant over a range of protein concentration, if the ratio of the concentration of the substrate to the protein was kept constant. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,BETHESDA,MD 20892. NR 25 TC 18 Z9 20 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 JUN PY 1995 VL 23 IS 6 BP 651 EP 654 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RD480 UT WOS:A1995RD48000009 PM 7587947 ER PT J AU MAYES, LC BORNSTEIN, MH AF MAYES, LC BORNSTEIN, MH TI INFANT INFORMATION-PROCESSING PERFORMANCE AND MATERNAL EDUCATION SO EARLY DEVELOPMENT & PARENTING LA English DT Article DE MATERNAL EDUCATION; SES; HABITUATION; NOVELTY RESPONSIVENESS ID SOCIOECONOMIC-STATUS; MENTAL-DEVELOPMENT; SOCIAL-CLASS; FULL-TERM; PREDICTORS; HABITUATION; IQ; PRETERM; VALUES; AGE AB Relations between maternal education and indices of infant information-processing performance were examined. A sample of 93 3-month olds whose mothers' completed education level was adequately distributed were seen in an infant control habituation procedure. Eighteen infants failed to complete the procedure, and 76 reached a conventional habituation criterion. No significant differences in habituation performance by maternal education level emerged. This finding suggests that information-processing indices obtained in the first 6 months are useful as predictive measures of mental development that are uncorrelated with important markets of infants' environmental rearing conditions. C1 NICHHD,BETHESDA,MD 20892. RP MAYES, LC (reprint author), YALE UNIV,CTR CHILD STUDY,230 S FRONTAGE RD,NEW HAVEN,CT 06510, USA. NR 42 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-3593 J9 EARLY DEV PARENTING JI Early Dev. Parenting PD JUN PY 1995 VL 4 IS 2 BP 91 EP 96 DI 10.1002/edp.2430040206 PG 6 WC Psychology, Developmental SC Psychology GA RF670 UT WOS:A1995RF67000005 ER PT J AU CHANG, HT CHRAMBACH, A AF CHANG, HT CHRAMBACH, A TI DISPERSION COEFFICIENTS OF A PROTEIN AND DNA FRAGMENT IN POLYACRYLAMIDE-GEL ELECTROPHORESIS AS A FUNCTION OF PARAMETERS DEFINING THE EFFECTIVE GEL PORE-SIZE AND PARTICLE-SIZE SO ELECTROPHORESIS LA English DT Article DE BAND DISPERSION; POLYACRYLAMIDE GEL; UNCROSSLINKED POLYACRYLAMIDE SOLUTIONS AB The dispersion coefficient, D', of the representative homogeneous protein, conalbumin, decreases linearly as the polyacrylamide concentration increases from 4 to 14%T (2%C), and varies in a biphasic fashion as %C (Bis) is increased from 2 to 20%, with a broad peak between 5 and 15%C. D' increases linearly with the concentration of the initiator, potassium persulfate, in the range of 0.01-0.15%. D' remains constant when the field strength is varied from 5 to 15 V/cm. A DNA fragment (1857 bp) exhibits a constant D' in 4-6% polyacrylamide (2%C) at a field strength of 1 V/cm, and a linearly increasing D' at 5 V/cm, in analogy to its previously observed behavior in agarose gels. In solutions of uncrosslinked polyacrylamide, the decrease of the D' of conalbumin with polymer concentration is not significantly different from that in 2% N,N-methylenebisacrylamide-crosslinked gels in the range of 4-14%T, while the decrease of mobility with polyacrylamide concentration is much steeper in 2% crosslinked compared to uncrosslinked polymer. Finally, -partial derivative (log D')partial derivative T was found to be proportional to the retardation coefficient, K-R (= -partial derivative (log mu)/partial derivative T), in polyacrylamide gels. The ratio of -partial derivative (log D')partial derivative T over K-R increases with field strength in the range of 5-15 V/cm. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 12 TC 6 Z9 6 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1995 VL 16 IS 6 BP 895 EP 898 DI 10.1002/elps.11501601150 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RK653 UT WOS:A1995RK65300003 PM 7498132 ER PT J AU CHANG, HT CHRAMBACH, A AF CHANG, HT CHRAMBACH, A TI HORIZONTAL GEL-ELECTROPHORESIS WITH SAMPLE VOLUMES UP TO 1.5 ML, USING A DISCONTINUOUS BUFFER SYSTEM AND AUTOMATED APPARATUS SO ELECTROPHORESIS LA English DT Article DE ELECTROPHORESIS; STACKING; SAMPLE VOLUME CAPACITY; AUTOMATED APPARATUS ID POLYACRYLAMIDE AB Horizontal gel electrophoresis has previously suffered from lack of an instrumental design that would allow for application of large sample volumes. A recently introduced commercial apparatus (HPGE-1000, LabIntelligence) remedies that problem in application to gel electrophoresis with intermittent scanning of fluorescence by using the concentrator module of that apparatus as a stacking gel reservoir. By using this technique and a 3 mL stacking gel, protein samples of up to 1.5 mL yield bands in the horizontal resolving gel that are independent of sample volume in their width, area and migration rate. A remaining procedural problem relates to the apparent nonsimultaneity of dye and protein entrance into the resolving gel, which necessitates peak characterization by absolute rather than relative mobilities. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 13 TC 4 Z9 4 U1 0 U2 1 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 JUN PY 1995 VL 16 IS 6 BP 952 EP 957 DI 10.1002/elps.11501601160 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RK653 UT WOS:A1995RK65300013 PM 7498142 ER PT J AU RADKO, SP SOKOLOFF, AV GARNER, MM CHRAMBACH, A AF RADKO, SP SOKOLOFF, AV GARNER, MM CHRAMBACH, A TI CAPILLARY ELECTROPHORESIS OF RAT-LIVER MICROSOMES IN POLYMER-SOLUTIONS SO ELECTROPHORESIS LA English DT Article DE MICROSOMES; CAPILLARY ELECTROPHORESIS; POLYMER SOLUTIONS; MICROSOME FUSION; MICROSOME SIZE ID GEL ELECTROPHORESIS; VESICLES; MOBILITY AB Rat liver microsome components were separated by capillary zone elctrophoresis in buffers containing substituted agarose, agarose crosslinked polyacrylamide, polyacrylamide, polyethylene glycol and dextran of various molecular weights. The best resolution of the components was obtained with polymers of 10-21 nm geometric mean radius. Both the crude and the purified preparations of microsomes exhibit a single major peak. In a Tris-borate-EDTA (TEE) buffer, containing polyacrylamide of 5 X 10(6) molecular weight, it has a retardation coefficient, K-R of 0.77 +/- 0.02. Translation of the K-R value to geometric mean radii, R, on the basis of the standard curve applicable to polymer solutions, K-R vs. R, with polystyrene carboxylate size standards in both dextran and polyacrylamide solution allows one to estimate a value of R as 13-16 nm for the major microsome component. The value is smaller than expected from electron microscopic measurements (100-250 nm), possibly due to the chemical and geometric differences between microsomes and the polystyrene particles used as size standards. The crude preparation also contains a minor component which is smaller and less charged than the major component. Another component, apparently very much larger than the major one, is seen in TEE buffer but not in a potassium-N-(2-hydroxyethyl)piperazine-2'-(2-ethanesulfonic acid) buffer and is therefore thought to be an artifact of interaction with borate. After a short incubation under conditions promoting delayed microsome fusion, i.e, in presence of GTP and Mg++ and in the absense of polyethylene glycol, the electrophoretic pattern changes dramatically: it now exhibits five unretarded, highly mobile and, therefore, presumably large components in addition to the two original retarded components of the microsome and a less highly charged species similar in K-R to the smaller of the original two components. C1 NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. NR 16 TC 17 Z9 18 U1 0 U2 4 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 JUN PY 1995 VL 16 IS 6 BP 981 EP 992 DI 10.1002/elps.11501601164 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RK653 UT WOS:A1995RK65300017 PM 7498146 ER PT J AU SIOMI, MC SIOMI, H SAUER, WH SRINIVASAN, S NUSSBAUM, RL DREYFUSS, G AF SIOMI, MC SIOMI, H SAUER, WH SRINIVASAN, S NUSSBAUM, RL DREYFUSS, G TI FXR1, AN AUTOSOMAL HOMOLOG OF THE FRAGILE-X MENTAL-RETARDATION GENE SO EMBO JOURNAL LA English DT Article DE CHROMOSOMAL MAPPING; FMR1; FRAGILE X MENTAL RETARDATION SYNDROME; FXR1; KH DOMAINS ID T7 RNA-POLYMERASE; CGG-REPEAT; FMR-1 GENE; EXPRESSION; PROTEIN; BINDING; DNA; CHROMOSOME-12; INSTABILITY; DOMAINS AB Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding, We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMP1, contains two KH domains and is highly conserved in vertebrates, The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are Strikingly conserved (similar to 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini, FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1, These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1. C1 UNIV PENN,SCH MED,HOWARD HUGHES MED INST,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Siomi, Haruhiko/A-7020-2015 OI Siomi, Haruhiko/0000-0001-8690-3822 NR 43 TC 161 Z9 168 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1995 VL 14 IS 11 BP 2401 EP 2408 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RC664 UT WOS:A1995RC66400001 PM 7781595 ER PT J AU LEROITH, D AF LEROITH, D TI EDITORIAL - A NOVEL DROSOPHILA INSULIN-RECEPTOR - FLY IN THE OINTMENT OR EVOLUTIONARY CONSERVATION SO ENDOCRINOLOGY LA English DT Editorial Material ID PEPTIDE; EXPRESSION; PRECURSOR; PROTEIN; CLONING RP LEROITH, D (reprint author), NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892, USA. NR 19 TC 2 Z9 2 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 JUN PY 1995 VL 136 IS 6 BP 2355 EP 2356 DI 10.1210/en.136.6.2355 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400001 PM 7750455 ER PT J AU MERCHENTHALER, I LENNARD, DE CIANCHETTA, P MERCHENTHALER, A BRONSTEIN, D AF MERCHENTHALER, I LENNARD, DE CIANCHETTA, P MERCHENTHALER, A BRONSTEIN, D TI INDUCTION OF PROENKEPHALIN IN TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS BY HYPERPROLACTINEMIA - THE ROLE OF SEX STEROIDS SO ENDOCRINOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; PROLACTIN SECRETION INVITRO; ENDOGENOUS OPIOID-PEPTIDES; RAT HYPOTHALAMUS; TYROSINE-HYDROXYLASE; MEDIAN-EMINENCE; GROWTH-HORMONE; MESSENGER-RNA; BETA-ENDORPHIN; IMMUNOREACTIVE NEURONS AB The observation that tuberoinfundibular dopaminergic (TIDA) neurons of pregnant, pseudopregnant, lactating, and aged rats express enkephalins suggested that chronically elevated PRL levels, which are characteristic for these animals, are essential for the induction of proenkephalin gene expression in TIDA neurons. The present studies investigated further the role of PRL in this phenomenon. Elevated PRL levels were achieved either experimentally by implanting anterior pituitaries under the kidney capsule of intact or hypophysectomized female rats or by using lactating rats. For controls, the elevated PRL levels were reduced with bromocryptine, a dopamine receptor agonist. The role of sex steroids in PRL-induced enkephalin gene expression was also studied in cycling, sex hormone-treated, hypophysectomized or ovariectomized rats, pituitary-implanted/sex hormone-treated rats, and ovariectomized mothers. Enkephalin immunoreactivity was detected by immunocytochemistry and enkephalin messenger RNA with in situ hybridization histochemistry using S-35- or digoxigenin-labeled riboprobes. Enkephalin or its messenger RNA was present in TIDA neurons in all experimental animals with elevated PRL levels. Although estradiol had no or only a minor effect on PRL-induced enkephalin gene expression, progesterone supported the effect of PRL. The present observations suggest that the expression of enkephalin in TIDA neurons is PRL dependent and supported by sex steroids, primarily progesterone. C1 NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, FUNCT MORPHOL SECT, RES TRIANGLE PK, NC 27709 USA. NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, PHARMACOL SECT, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, DEPT PEDIAT, CHAPEL HILL, NC 27599 USA. NR 69 TC 23 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1995 VL 136 IS 6 BP 2442 EP 2450 DI 10.1210/en.136.6.2442 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400013 PM 7750466 ER PT J AU SONG, WC MOORE, R MCLACHLAN, JA NEGISHI, M AF SONG, WC MOORE, R MCLACHLAN, JA NEGISHI, M TI MOLECULAR CHARACTERIZATION OF A TESTIS-SPECIFIC ESTROGEN SULFOTRANSFERASE AND ABERRANT LIVER EXPRESSION IN OBESE AND DIABETOGENIC C57BL/KSJ-DB/DB MICE SO ENDOCRINOLOGY LA English DT Article ID DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; STEROID SULFOTRANSFERASES; SEQUENCE-ANALYSIS; MOUSE-LIVER; GUINEA-PIG; RAT-LIVER; CLONING; CDNA; FORM; SULFATASES AB Sulfation represents a major pathway for the inactivation of steroid hormones such as estrogens and is catalyzed by a group of enzymes called sulfotransferases. Aberrant regulation of an estrogen sulfotransferase has been demonstrated previously in the livers of obese and diabetogenic C57BL/KsJ-db/db strain mice. In this paper, we report the molecular cloning and functional characterization of a full-length complementary DNA for estrogen sulfotransferase from mouse testis. The mouse estrogen sulfotransferase complementary DNA encodes 295 amino acids. It shares 88%, 77%, 75%, and 68% identity in amino acid sequence with the rat liver, human liver, guinea pig adrenal, and bovine placental estrogen sulfotransferase, respectively. The mouse enzyme was expressed as a glutathione-S-transferase fusion protein in Escherichia coli. The fusion protein was affinity purified, and milligram quantities of pure enzyme were obtained after cleavage of the fusion protein with thrombin. The expressed enzyme exhibits a high substrate specificity toward estrogens, including estradiol and estrone. Neither dehydroepiandrosterone, pregnenolone, testosterone, nor a simple phenolic compound, 4-nitrophenol appears to be a substrate. Northern hybridization indicates that messenger RNA (1.3 kilobases) for the estrogen sulfotransferase is expressed exclusively in the testes in control G57BL/KsJ mice. However, both the messenger RNA and protein are dramatically induced in the livers of obese and diabetogenic C57BL/KsJ-db/db mice. In contrast to the liver, the constitutive expression of the enzyme in the testis is not affected by the db/db genotype. These results recapitulate the species-specific nature in the tissue distribution of estrogen sulfotransferase and suggest complex regulatory mechanisms in its expression under normal and pathophysiological conditions. RP SONG, WC (reprint author), NIEHS, REPROD & DEV TOXICOL LAB, PHARMACOGENET SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 27 TC 82 Z9 83 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1995 VL 136 IS 6 BP 2477 EP 2484 DI 10.1210/en.136.6.2477 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400018 PM 7750469 ER PT J AU KLEINMAN, D KARAS, M ROBERTS, CT LEROITH, D PHILLIP, M SEGEV, Y LEVY, J SHARONI, Y AF KLEINMAN, D KARAS, M ROBERTS, CT LEROITH, D PHILLIP, M SEGEV, Y LEVY, J SHARONI, Y TI MODULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) RECEPTORS AND MEMBRANE-ASSOCIATED IGF-BINDING PROTEINS IN ENDOMETRIAL CANCER-CELLS BY ESTRADIOL SO ENDOCRINOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; AUTOCRINE; HORMONE; ANALOGS; RAT; PHYSIOLOGY; ESTROGEN AB Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [I-125]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [I-125]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [I-125]des-(1-3)IGF-I as the ligand. Des-(1-3)IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [I-125]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [I-125]IGF-I and [I-125]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,SOROKA MED CTR KUPAT HOLIM,FAC HLTH SCI,CTR PEDIAT DIAGNOST & THERAPEUT,IL-84105 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,SOROKA MED CTR KUPAT HOLIM,FAC HLTH SCI,DEPT CLIN BIOCHEM,IL-84105 BEER SHEVA,ISRAEL. OI Roberts, Charles/0000-0003-1756-5772 NR 32 TC 64 Z9 65 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 JUN PY 1995 VL 136 IS 6 BP 2531 EP 2537 DI 10.1210/en.136.6.2531 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400024 PM 7750475 ER PT J AU WANG, EM WANG, J CHIN, E ZHOU, JA BONDY, CA AF WANG, EM WANG, J CHIN, E ZHOU, JA BONDY, CA TI CELLULAR-PATTERNS OF INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION IN MURINE CHONDROGENESIS AND OSTEOGENESIS SO ENDOCRINOLOGY LA English DT Article ID II MANNOSE-6-PHOSPHATE RECEPTOR; LONGITUDINAL BONE-GROWTH; FACTOR BINDING-PROTEINS; IGF-I; HYPOPHYSECTOMIZED RATS; LARON-TYPE; CHONDROCYTES; HORMONE; MULTIPLICATION; ANATOMY AB In situ hybridization histochemistry was used to map cellular patterns of gene expression for the insulin-like growth factor (IGF) system in developing murine skeleton from embryonic day 15 (E15) through postnatal day 25 (P25). IGF-I receptor and IGF-II receptor messenger RNAs (mRNAs) are both selectively concentrated in developing chondrocytes and osteoblasts. IGF-II and IGF-binding protein-5 and -6 (IGFBP-5 and -6) mRNAs are abundant in mesenchymal condensations and chondroblasts on E15. Chondrocyte IGF-II mRNA levels remain high, but IGFBP-5 and -6 mRNAs decline significantly as cartilage matures. Low levels of IGFBP-6 mRNA are detected in postnatal chondrocytes up to at least P25, but IGFBP-5 mRNA is no longer detected in chondrocytes after E18. IGF-I and IGFBP-2, -3, and -4 mRNAs are detected in surrounding mesenchymal tissue, but are not detected in mesenchymal condensations or chondrocytes at any stage of development. IGFBP-3 mRNA is localized in sprouting capillaries invading the perichondrium and periosteum throughout development. IGF-I, IGF-II, and IGFBP-2, -4, -5, and -6 mRNAs are detected in osteoblasts localized in zones of endochondral ossification from E18 to at least P25. IGFBP-1 mRNA is not detected in cartilage or bone cells at any stage of development. These data confirm the recent report by Shinar et al. that IGF-II, but not IGF-I, mRNA is detected in rat chondrocytes in vivo and show that this pattern also applies to the mouse. The present study demonstrates, for the first time, the cell-specific patterns of IGF-I and -II receptor and IGFBP-2- to -6 gene expression during the processes of chondro- and osteogenesis in vivo. Interestingly, IGF-II, both IGF receptors, and IGFBP-5 and -6 are simultaneously coexpressed in chondrocyte precursors early in skeletal development, suggesting functional interactions between these specific factors in chondrogenesis. Both IGFs, both IGF receptors, and IGFBP-2, -4, -5, and -6 are all expressed in osteoblasts, providing evidence for potential local interactions between these IGF system components in osteogenesis. Thus, 9 of 10 known components of the IGF system demonstrate dynamic cell-specific patterns of gene expression during chondro- and osteogenesis, supporting the view that the IGF system has a complex and integral role within the developing skeleton. RP WANG, EM (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 38 TC 105 Z9 105 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 JUN PY 1995 VL 136 IS 6 BP 2741 EP 2751 DI 10.1210/en.136.6.2741 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400050 PM 7750499 ER PT J AU Young, L Suk, W AF Young, L Suk, W TI Biodegradation: Its role in reducing toxicity and exposure to environmental contaminants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 Rutgers State Univ, Ctr Agr Mol Biol, New Brunswick, NJ 08903 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Young, L (reprint author), Rutgers State Univ, Ctr Agr Mol Biol, New Brunswick, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1995 VL 103 SU 5 BP 3 EP 3 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AS UT WOS:000202841000001 PM 8565905 ER PT J AU HASEMAN, JK AF HASEMAN, JK TI COMPACT PREDICTIONS - IS THERE A CATCH SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter RP HASEMAN, JK (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 0 Z9 0 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 JUN PY 1995 VL 103 IS 6 BP 536 EP 537 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RW441 UT WOS:A1995RW44100002 PM 7555997 ER PT J AU ROGAWSKI, MA LE, DQ UYAKUL, D PANNELL, LK SUBRAMANIAM, S YAMAGUCHI, SI KOKATE, TG AF ROGAWSKI, MA LE, DQ UYAKUL, D PANNELL, LK SUBRAMANIAM, S YAMAGUCHI, SI KOKATE, TG TI ANTICONVULSANT EFFICACY OF ADCI (5-AMINOCARBONYL-LO,11-DIHYDRO-5H-DIBENZO[A,D] CYCLOHEPTEN-5,10-IMINE) AFTER ACUTE AND CHRONIC DOSING IN MICE SO EPILEPSIA LA English DT Article DE ANTICONVULSANT DRUG; TOLERANCE; MOUSE; MAXIMAL ELECTROSHOCK TEST; [H-3] DIZOCILPINE BINDING ID (+/-)-5-AMINOCARBONYL-10,11-DIHYDRO-5H-DIBENZOCYCLOHEPTEN-5,10-IMIN E ADCI; NMDA RECEPTOR; CARBAMAZEPINE; TOLERANCE; MK-801; DIZOCILPINE; DIAZEPAM; EPILEPSY; RATS AB ADCI (5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), a low-affinity uncompetitive N-methyl-D-aspartate (NMDA) antagonist, is a broad-spectrum anticonvulsant with a favorable side-effect profile. In the present study, we sought to determine if tolerance develops to the anticonvulsant activity of ADCI, using the maximal electroshock (MES) test to assess seizure protection. Mice were treated with three daily injections of a 2 x ED(50) dose for MES protection (18 mg/kg, intraperitoneally, i.p.) or vehicle for 7 or 14 days. On the day after the chronic treatment protocol, all animals received a challenge dose of ADCI (18 mg/kg) and 15 min later were evaluated in the MES test. In control animals, 83-94% of animals were protected and the ADCI plasma levels immediately after the MES test were 5.5-9.7 mu g/ml. In treated animals, 29 and 0% of animals were protected at 7 and 14 days, respectively, and the ADCI plasma levels were 77 and 52% of the control values, [H-3]Dizocilpine binding to brain NMDA receptors was unaltered by the chronic drug treatment. In subsequent experiments, we determined that 14-day chronically treated animals could be completely protected by increased doses of ADCI (ED(50) 28.9 mg/kg). In both naive and chronically treated animals receiving a challenge dose of ADCI, plasma drug levels decreased in two phases, the first with a time constant of similar to 55 min and the second with a much slower rate. The estimated plasma concentrations of ADCI reflecting threshold (3-5 mu g/ml) and 50% protection (5-7.5 mu g/mg) were similar in naive and chronic animals. We conclude that tolerance to ADCI is due to pharmacokinetic factors (enhanced first-pass metabolism) and does not result from a reduction in anticonvulsant efficacy. C1 NIDDKD,ANALYT CHEM LAB,BETHESDA,MD 20892. RP ROGAWSKI, MA (reprint author), NINCDS,EPILEPSY BRANCH,NEURONAL EXCITABIL SECT,BLDG 10,ROOM 5C-205,BETHESDA,MD 20892, USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 17 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 1995 VL 36 IS 6 BP 566 EP 571 DI 10.1111/j.1528-1157.1995.tb02568.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RA386 UT WOS:A1995RA38600004 PM 7555968 ER PT J AU OKUN, MM FITZGIBBON, J NAHASS, GT FORSMAN, K AF OKUN, MM FITZGIBBON, J NAHASS, GT FORSMAN, K TI ALEUKEMIC LEUKEMIA-CUTIS, MYELOID SUBTYPE SO EUROPEAN JOURNAL OF DERMATOLOGY LA English DT Article DE CUTANEOUS TUMORS; LEUKEMIA CUTIS GRANULOCYTE SARCOMA; ALEUKEMIA ID ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE MONOCYTIC LEUKEMIA; GRANULOCYTIC SARCOMA; SKIN; MANIFESTATIONS AB Two case histories of patients with aleukemic leukemia cutis, myeloid subtype, are reported. Both patients presented with cutaneous leukemic tumors. One patient is in spontaneous clinical remission three and a half years after his cutaneous lesions appeared, while the other patient is in a chemotherapy-induced clinical remission of six months' duration. These represent the nineteenth and twentieth reported cases of aleukemic leukemia cutis. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. ST LOUIS UNIV,SCH MED,DIV DERMATOL,ST LOUIS,MO. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RP OKUN, MM (reprint author), WASHINGTON UNIV,SCH MED,DIV DERMATOL,ST LOUIS,MO 63110, USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1167-1122 J9 EUR J DERMATOL JI Eur. J. Dermatol. PD JUN PY 1995 VL 5 IS 4 BP 290 EP 293 PG 4 WC Dermatology SC Dermatology GA RF550 UT WOS:A1995RF55000004 ER PT J AU WHITCUP, SM HIKITA, N SHIRAO, M MIYASAKA, M TAMATANI, T MOCHIZUKI, M NUSSENBLATT, RB CHAN, CC AF WHITCUP, SM HIKITA, N SHIRAO, M MIYASAKA, M TAMATANI, T MOCHIZUKI, M NUSSENBLATT, RB CHAN, CC TI MONOCLONAL-ANTIBODIES AGAINST CD54 (ICAM-1) AND CD11A (LFA-1) PREVENT AND INHIBIT ENDOTOXIN-INDUCED UVEITIS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE CELL ADHESION MOLECULES; CD54 (ICAM-1); CD11A (LFA-1); INFLAMMATION; UVEITIS; EYE; ENDOTOXIN ID RAT; NEUTROPHILS; INDUCTION; CYTOKINE AB We studied the effect of monoclonal antibodies (mAbs) against CD54 (intercellular adhesion molecule-1; ICAM-1) and CD11a (lymphocyte function-associated antigen-1; LFA-1) on the prevention and treatment of endotoxin-induced uveitis (EIU). When treated at the time of endotoxin injection the mean number of inflammatory cells infiltrating the eye+/-S.E.M. on histologic sections was 469.2+/-51.9 for controls, 13.8+/-2.6 for rats receiving anti-ICAM-1 mAb (P<0.0001), and 195.8+/-48.8 for rats receiving anti-LFA-1 mAb (P=0.0003). When treated after the start of inflammatory disease, the mean number of infiltrating inflammatory cells+/-S.E.M. was 273.0+/-30.7 for controls, 6.4+/-1.7 for rats receiving anti-ICAM-1 mAb (P<0.0001), and 54.2+/-7.6 for rats receiving anti-LFA-1 mAb (P<0.0001). The mean number of cells per milliliter of aqueous humor+/-S.E.M. was 1867.6+/-321.8 for controls, 21.7+/-5.3 for rats receiving anti-ICAM-1 mAb (P<0.0001), and 295.1+/-71.2 for rats receiving anti-LFA-1 mAb (P<0.0001). MAbs against ICAM-1 and LFA-1 significantly inhibited the development of EIU and were effective in treating clinically evident ocular inflammatory disease. C1 KURUME UNIV,SCH MED,DEPT OPHTHALMOL,FUKUOKA,JAPAN. TOKYO METROPOLITAN INST MED SCI,DEPT IMMUNOL,TOKYO 113,JAPAN. RP WHITCUP, SM (reprint author), NEI,BLDG 10 RM 10N 202,BETHESDA,MD 20892, USA. NR 17 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 1995 VL 60 IS 6 BP 597 EP 601 DI 10.1016/S0014-4835(05)80001-6 PG 5 WC Ophthalmology SC Ophthalmology GA RB660 UT WOS:A1995RB66000001 PM 7641842 ER PT J AU VINORES, SA HENDERER, JD MAHLOW, J CHIU, C DEREVJANIK, NL LAROCHELLE, W CSAKY, C CAMPOCHIARO, PA AF VINORES, SA HENDERER, JD MAHLOW, J CHIU, C DEREVJANIK, NL LAROCHELLE, W CSAKY, C CAMPOCHIARO, PA TI ISOFORMS OF PLATELET-DERIVED GROWTH-FACTOR AND ITS RECEPTORS IN EPIRETINAL MEMBRANES - IMMUNOLOCALIZATION TO RETINAL PIGMENTED EPITHELIAL-CELLS SO EXPERIMENTAL EYE RESEARCH LA English DT Article ID FACTOR GENE-EXPRESSION; SMOOTH-MUSCLE CELLS; PROLIFERATIVE VITREORETINOPATHY; DIABETIC-RETINOPATHY; PDGF-B; MONOCLONAL-ANTIBODIES; LOCALIZATION; FIBROBLASTS; PROTEINS; GLIA AB Epiretinal membranes (ERMs) form on the inner surface of the retina in conjunction with various ocular disease processes, but the factors controlling their development are not understood. The predominant cell types involved are retinal pigmented epithelial (RPE) cells and retinal glia. Cultured RPE cells secrete platelet-derived growth factor (PDGF), which is chemotactic and mitogenic for both RPE cells and retinal glia and, therefore, could be involved in the development of ERMs. In the present study, we performed immunohistochemical staining for PDGF A chain (PDGF-A), PDGF B chain (PDGF-B), and both types of PDGF receptors (PDGF(r alpha) and PDGF(r beta)) on ERMs associated with various disease processes. PDGF-A is detected in most ERMs, regardless of the associated disease process, and it appears to be localized predominantly in RPE cells, recognized by the presence of pigment and the immunohistochemical demonstration of some or all of the following RPE-associated epitopes: class III beta-tubulin, keratin, the 65-kDa microsomal protein recognized by the RPE9 antibody, and cellular retinaldehyde-binding protein. PDGF-B is found only in minor subpopulations of cells in about half of the ERMs evaluated and, with only occasional exceptions, appears to be localized almost entirely in brood-borne cells found in and around vessels in vascularized ERMs. Both PDGF(r alpha) and PDGF(r beta) are demonstrated in most ERMs with neither isotype consistently predominating: they are found predominantly on RPE cells with many cells expressing both receptor types. ERMs with little or no RPE cell component contain little or no PDGF and PDGF receptor, whereas those in which the RPE cell represents the major cell type, have widespread PDGF and PDGF receptor positivity. These findings show that RPE cells in ERMs produce PDGF-A and PDGF(alpha) and PDGF(beta) receptors and suggest that autocrine and paracrine stimulation with PDGF may be involved in ERM pathogenesis. C1 NIH,BETHESDA,MD 20892. RP VINORES, SA (reprint author), JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,825 MAUMENEE BLDG,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NEI NIH HHS [EY05951, EY10017, P30EY01765] NR 58 TC 48 Z9 51 U1 0 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 1995 VL 60 IS 6 BP 607 EP 619 DI 10.1016/S0014-4835(05)80003-X PG 13 WC Ophthalmology SC Ophthalmology GA RB660 UT WOS:A1995RB66000003 PM 7641844 ER PT J AU SMALE, G NICHOLS, NR BRADY, DR FINCH, CE HORTON, WE AF SMALE, G NICHOLS, NR BRADY, DR FINCH, CE HORTON, WE TI EVIDENCE FOR APOPTOTIC CELL-DEATH IN ALZHEIMERS-DISEASE SO EXPERIMENTAL NEUROLOGY LA English DT Article ID DNA FRAGMENTATION AB We provide evidence for apoptosis in Alzheimer's disease using the in situ labeling technique TUNEL (terminal transferase-mediated dUTP-biotin nick end labeling). The technique specifically detects apoptotic cells by utilizing terminal transferase to incorporate biotinylated nucleotides into the fragmented DNA of apoptotic cells. The labeled cells are visualized by reaction with avidin peroxidase and a suitable substrate. Sections from the hippocampus of Alzheimer-diseased (AD) brains and non-AD brains were examined for apoptosis. While considerable variation in the quantity of apoptotic cells was observed among individual samples, the incidence of apoptosis in AD brains was elevated in comparison to age-matched, non-AD brains in specific regions of the hippocampal formation. Immunostaining indicated that both neurons and astrocytes were undergoing apoptosis, although the majority of the TUNEL-positive cells appeared to be glial, based on the location of the stained cells. These data suggest that apoptosis may be involved in both the primary neuronal cell loss and in the glial response that is a component of AD. (C) 1995 Academic Press, Inc. C1 UNIV SO CALIF,CTR ANDRUS GERONTOL,LOS ANGELES,CA 90089. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP SMALE, G (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 13 TC 376 Z9 411 U1 1 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 1995 VL 133 IS 2 BP 225 EP 230 DI 10.1006/exnr.1995.1025 PG 6 WC Neurosciences SC Neurosciences & Neurology GA RP124 UT WOS:A1995RP12400013 PM 7544290 ER PT J AU VERNICK, KD FUJIOKA, H SEELEY, DC TANDLER, B AIKAWA, M MILLER, LH AF VERNICK, KD FUJIOKA, H SEELEY, DC TANDLER, B AIKAWA, M MILLER, LH TI PLASMODIUM-GALLINACEUM - A REFRACTORY MECHANISM OF OOKINETE KILLING IN THE MOSQUITO, ANOPHELES-GAMBIAE SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE ANOPHELES GAMBIAE; PLASMODIUM GALLINACEUM; MALARIA; VECTOR COMPETENCE; GENETICS; INSECT IMMUNITY; MOSQUITOS; REFRACTORY; MIDGUT ID AEDES-AEGYPTI; MALARIA; SUSCEPTIBILITY; TRANSMISSION; ASSOCIATION; ANTIBODIES; CYNOMOLGI; STRAIN; MIDGUT AB We have identified a mechanism for refractoriness to a bird malaria, Plasmodium gallinaceum, in the African vector of human malaria, Anopheles gambiae. Oocysts fail to develop in the refractory mosquitoes as a result of ookinete death which occurs within 27 hr of midgut invasion, Ultrastructural studies showed that parasite death occurs while the ookinete lies free in the midgut epithelial cell cytosol, usually surrounded by an organelle-free zone that consists of finely fibrillar material. The mechanism of parasite killing does not involve a previously described refractory mechanism of parasite encapsulation. We selected genetic lines which are refractory and susceptible to midgut infection. Genetic crossing of the lines suggests that the refractory trait is inherited as a single dominant genetic locus. Other loci probably influence oocyst number in susceptible mosquitoes. Intracellular ookinete killing appears to involve a previously unrecognized host defense mechanism against malaria parasites that involves direct destruction of the invading organism. (C) 1995 Academic Press, Inc. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. RP VERNICK, KD (reprint author), NIAID,MALARIA RES LAB,MOLEC ENTOMOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-10645-22] NR 21 TC 131 Z9 135 U1 2 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 1995 VL 80 IS 4 BP 583 EP 595 DI 10.1006/expr.1995.1074 PG 13 WC Parasitology SC Parasitology GA RA728 UT WOS:A1995RA72800001 PM 7758539 ER PT J AU KOZIKOWSKI, AP MA, DW DU, L LEWIN, NE BLUMBERG, PM AF KOZIKOWSKI, AP MA, DW DU, L LEWIN, NE BLUMBERG, PM TI EFFECT OF ALTERATION OF THE HETEROCYCLIC NUCLEUS OF ILV ON ITS ISOFORM SELECTIVITY FOR PKC - PALLADIUM-CATALYZED ROUTE TO BENZOFURAN ANALOGS OF ILV SO FARMACO LA English DT Article; Proceedings Paper CT 10th Camerino-Noordwijkerhout Symposium on Perspectives in Receptor Research CY SEP 10-14, 1995 CL CAMERINO, ITALY SP Italian Chem Soc, European Fed Med Chem, Univ Camerino ID PROTEIN-KINASE-C; CELLS; ALPHA; ACTIVATION; EPSILON; DIACYLGLYCEROL; OVEREXPRESSION; TRANSLOCATION; ISOENZYMES; ISOZYMES AB A palladium catalyzed route for the preparation of several benzofuran analogues of the PKC activator indolactam V (ILV) is described together with the ability of these compounds to activate the isoforms of PKC. The benzofuran analogues of ILV are shown to activate PKC with a slightly different pattern of isotype selectivity than ILV or 7-n-octyl-ILV. Moreover, in an examination of the effect of stereochemistry at the C-14 center of the teleocidins on PKC binding activity, a clear preference for R-stereochemistry at the C-14 center was found, thus providing additional verification of previously published structural correlations between the families of PKC activators. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RP KOZIKOWSKI, AP (reprint author), MAYO FDN MED EDUC & RES,4500 SAN PAOLO RD,JACKSONVILLE,FL 32224, USA. NR 38 TC 6 Z9 6 U1 0 U2 0 PU SOC CHIMICA ITALIANA PI ROME PA VIALE LIEGI 48, I-00198 ROME, ITALY SN 0014-827X J9 FARMACO JI Farmaco PD JUN PY 1995 VL 50 IS 6 BP 425 EP 430 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RM645 UT WOS:A1995RM64500008 PM 7669180 ER PT J AU EUSTIS, SL HASEMAN, JK MACKENZIE, WF ABDO, KM AF EUSTIS, SL HASEMAN, JK MACKENZIE, WF ABDO, KM TI TOXICITY AND CARCINOGENICITY OF 2,3-DIBROMO-1-PROPANOL IN F344/N RATS AND B6C3F(1) MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID FLAME-RETARDANT TRIS(2,3-DIBROMOPROPYL)PHOSPHATE; STATISTICAL ISSUES; TRIS-BP; METABOLISM; MUTAGENICITY; CHEMICALS; PHOSPHATE; DNA; S-<2-(N7-GUANYL)ETHYL>GLUTATHIONE; 1,2-DIBROMO-3-CHLOROPROPANE AB 2,3-Dibromo-1-propanol is a metabolite of the flame retardant tris(2,3-dibromopropyl) phosphate, previously shown to be a mutagen and carcinogen in experimental animals. Toxicology and carcinogenesis studies of 2,3-dibromo-1-propanol were conducted by applying the chemical in 95% ethanol to the interscapular skin of male and female F344/N rats and B6C3F(1) mice 5 days a week for 13 weeks in the prechronic study and 48-55 weeks (rats) or 36-42 weeks (mice) in the carcinogenicity study. In the 13-week study, 10 rats and 10 mice of each sex received doses of 0, 44, 88, 177, 375, or 750 mg/kg. Deaths associated with chemical application occurred only in the high-dose (750 mg/kg) male mice. Chemical-related lesions were seen in the kidney of male rats, liver of female rats, and liver and lung of both sexes of mice. Based on the toxicity observed in the 13-week study, 50 rats of each sex received doses of 0, 188, or 375 mg/kg and 50 mice of each sex received 0, 88, or 177 mg/kg in the carcinogenicity study. The planned 2-year study was terminated early because of reduced survival of rats related to chemical-induced neoplasia and because of the appearance of antibodies to lymphocytic choriomeningitis virus in sentinel mice. Nearly all dosed rats had malignant neoplasms at one or more sites, while only one control male and one control female had malignant neoplasms. In rats, neoplasms induced by 2,3-dibromo-1-propanol occurred in the skin, nasal mucosa, Zymbal's gland, oral mucosa, esophagus, forestomach, intestines, liver, kidney, mammary gland (females), clitoral gland (females), spleen (males), and mesothelium (males). In mice, chemical-induced neoplasms occurred in the skin, forestomach, liver (males), and lung (males). (C) 1995 Society of Toxicology. C1 EXPTL PATHOL LABS,RES TRIANGLE PK,NC 27709. RP EUSTIS, SL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUN PY 1995 VL 26 IS 1 BP 41 EP 50 DI 10.1006/faat.1995.1073 PG 10 WC Toxicology SC Toxicology GA RC852 UT WOS:A1995RC85200005 PM 7657061 ER PT J AU WEBER, HC VENZON, DJ LIN, JT FISHBEIN, VA ORBUCH, M STRADER, DB GIBRIL, F METZ, DC FRAKER, DL NORTON, JA JENSEN, RT AF WEBER, HC VENZON, DJ LIN, JT FISHBEIN, VA ORBUCH, M STRADER, DB GIBRIL, F METZ, DC FRAKER, DL NORTON, JA JENSEN, RT TI DETERMINANTS OF METASTATIC RATE AND SURVIVAL IN PATIENTS WITH ZOLLINGER-ELLISON SYNDROME - A PROSPECTIVE LONG-TERM STUDY SO GASTROENTEROLOGY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; MANAGEMENT; GASTRINOMA; TUMORS; DIAGNOSIS; SURGERY; CURE AB Background/Aims: It is unclear whether tumor location, size, or the presence of multiple endocrine neoplasia type 1 (MEN-1) alters metastatic rate and survival in patients with pancreatic endocrine tumors. The purpose of this study was to determine the prognostic factors of survival and metastatic rate in patients with Zollinger-Ellison syndrome (ZES). Methods: Data were analyzed from 185 consecutive patients with ZES who were followed up prospectively. Results: Liver metastases were present in 24% of patients and correlated with the size of the primary tumor. Duodenal tumors were smaller than pancreatic tumors. Liver metastases occurred more often (P < 0.00001) with pancreatic than duodenal tumors, whereas the metastatic rate to lymph nodes was not different. Survival of patients with liver but not lymph node metastases was shortened. In patients with sporadic ZES, liver metastases were move common during the initial evaluation and survival was decreased compared with patients with MEN-1; however, during follow-up, an equal percentage of patients with and without MEN-1 developed liver metastases. Conclusions: Survival was primarily determined by the presence of liver metastases. The frequency of liver metastases depends on the size and location of the primary tumor and on the presence of MEN-1 at the initial presentation. Metastases to the lymph nodes do not depend on these factors. A benign and malignant form of ZES exists. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD. NCI,SURG METAB SECT,SURG BRANCH,BETHESDA,MD. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO. RI Venzon, David/B-3078-2008 NR 47 TC 306 Z9 311 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1995 VL 108 IS 6 BP 1637 EP 1649 DI 10.1016/0016-5085(95)90124-8 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RA378 UT WOS:A1995RA37800005 PM 7768367 ER PT J AU BROTMAN, M GIANNELLA, RA ALM, PF BAUMAN, H BENNETT, AR BLACK, RE BRUHN, CM COHEN, MB GORBACH, SL KAPER, JB ROBERTS, MR STANECK, JL TAYLOR, S TROUTT, HF BELL, BP BUCHANAN, RL DURHAM, K FENG, P FORMAN, CT GALLER, RG GRAVANI, RB HALL, RB HANCOCK, DD HOLLINGSWORTH, J KARMALI, MA KEUSCH, GT MARSDEN, JL OSTERHOLM, MT REAGAN, JO ROBERTS, T SIEGLER, RL SWERDLOW, DL TARR, PI COWMAN, GL GOODFELLOW, SJ GRIFFIN, PM HALL, M HAMILTON, F HARRINGTON, RE KARR, KJ LANG, DR MADDEN, JM NORCROSS, MA SAVAGE, K SHANK, F TAYLOR, DN AF BROTMAN, M GIANNELLA, RA ALM, PF BAUMAN, H BENNETT, AR BLACK, RE BRUHN, CM COHEN, MB GORBACH, SL KAPER, JB ROBERTS, MR STANECK, JL TAYLOR, S TROUTT, HF BELL, BP BUCHANAN, RL DURHAM, K FENG, P FORMAN, CT GALLER, RG GRAVANI, RB HALL, RB HANCOCK, DD HOLLINGSWORTH, J KARMALI, MA KEUSCH, GT MARSDEN, JL OSTERHOLM, MT REAGAN, JO ROBERTS, T SIEGLER, RL SWERDLOW, DL TARR, PI COWMAN, GL GOODFELLOW, SJ GRIFFIN, PM HALL, M HAMILTON, F HARRINGTON, RE KARR, KJ LANG, DR MADDEN, JM NORCROSS, MA SAVAGE, K SHANK, F TAYLOR, DN TI CONSENSUS CONFERENCE STATEMENT - ESCHERICHIA-COLI O157-H7 INFECTIONS - AN EMERGING NATIONAL-HEALTH CRISIS, JULY 11-13, 1994 SO GASTROENTEROLOGY LA English DT Editorial Material ID HEMOLYTIC-UREMIC SYNDROME; HEMORRHAGIC COLITIS; 0157-H7; TOXIN; EPIDEMIOLOGY; PATHOGEN; DIARRHEA; CULTURES AB This statement was prepared by a nonadvocate panel of experts based an (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session, (2) questions and statements from conference attendees during open discussion periods that are part of the public session, and (3) closed deliberations by the panel during the remainder of the second dat and the morning of the third. This statement is an independent report of the panel and is not a policy statement of the American Gastroenterological Association, the American Gastroenterological Association Foundation (now known as the American Digestive Health Foundation) or the cosponsors listed at the end at this statement. C1 CALIF PACIFIC MED CTR,DEPT MED,SAN FRANCISCO,CA. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV DIGEST DIS,CINCINNATI,OH 45267. ALM CONSULTING SERV,SAN ANTONIO,TX. FOX BENNETT & TURNER,WASHINGTON,DC. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD. UNIV CALIF DAVIS,CTR CONSUMER RES,DAVIS,CA. CHILDRENS HOSP,MED CTR,DIV PEDIAT GASTROENTEROL & NUTR,CINCINNATI,OH 45229. TUFTS UNIV,SCH MED,BOSTON,MA 02111. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,DEPT MED,BALTIMORE,MD 21201. FLORIDA DEPT AGR & CONSUMER SERV,TALLAHASSEE,FL. UNIV CINCINNATI HOSP,DEPT PATHOL & LAB MED,CINCINNATI,OH. UNIV NEBRASKA,DEPT FOOD SCI & TECHNOL,LINCOLN,NE 68583. UNIV ILLINOIS,DEPT VET CLIN MED,URBANA,IL 61801. WASHINGTON DEPT HLTH,CTR DIS CONTROL & PREVENT,SEATTLE,WA. USDA ARS,EASTERN REG RES CTR,MICROBIAL FOOD SAFETY RES UNIT,PHILADELPHIA,PA 19118. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF CONSTITUENT OPERAT,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MICROBIOL STUDIES,WASHINGTON,DC 20204. FOREMAN & HEIDEPRIEM INC,WASHINGTON,DC. LOIS JOY GALLER FDN HEMOLYT UREM SYNDROME INC,VALLEY STREAM,NY. CORNELL UNIV,INST FOOD SCI,DEPT FOOD SCI,DIV FOOD SAFETY EXTENS,ITHACA,NY 14853. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. DEPT VET CLIN SCI,FIELD DIS INVEST UNIT,PULLMAN,WA. USDA,FOOD SAFETY & INSPECT SERV,WASHINGTON,DC 20250. HOSP SICK CHILDREN,DEPT MICROBIOL,TORONTO,ON M5G 1X8,CANADA. TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. AMI FDN,AMER MEAT INST,ARLINGTON,VA. MINNESOTA DEPT HLTH,ACUTE DIS & EPIDEMIOL SECT,MINNEAPOLIS,MN. NATL LIVE STEOCK & MEAT BOARD,DEPT RES MEAT SCI,DIV PROD TECHNOL,CHICAGO,IL. USDA,DIV ECON RES SERV,FOOD SAFETY & REGULAT SECT,WASHINGTON,DC 20250. UNIV UTAH,SCH MED,DEPT PEDIAT,DIV NEPHROL,SALT LAKE CITY,UT. CTR DIS CONTROL & PREVENT,FOODBORNE & DIARRHEAL DIS BRANCH,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30341. UNIV WASHINGTON,CHILDRENS HOSP & MED CTR,DEPT PEDIAT,DIV GASTROENTEROL,SEATTLE,WA. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV DIGEST DIS,CINCINNATI,OH 45267. CALIF PACIFIC MED CTR,DEPT MED,SAN FRANCISCO,CA. NATL CATTLEMENS ASSOC,ENGLEWOOD,CO. ABC RES CORP,DEPT MICROBIOL,GAINESVILLE,FL. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA. AMER GASTROENTEROL ASSOC FDN,BETHESDA,MD. NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. NATL RESTAURANT ASSOC,TECH SERV,WASHINGTON,DC. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. FOOD MKT INST,WASHINGTON,DC. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC. NR 55 TC 39 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1995 VL 108 IS 6 BP 1923 EP 1934 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RA378 UT WOS:A1995RA37800040 ER PT J AU HANANIA, EG FU, S RONINSON, I ZU, Z GOTTESMAN, MM DEISSEROTH, AB AF HANANIA, EG FU, S RONINSON, I ZU, Z GOTTESMAN, MM DEISSEROTH, AB TI RESISTANCE TO TAXOL CHEMOTHERAPY PRODUCED IN MOUSE MARROW-CELLS BY SAFETY-MODIFIED RETROVIRUSES CONTAINING A HUMAN MDR-1 TRANSCRIPTION UNIT SO GENE THERAPY LA English DT Article DE MDR-1; TRANSPLANTATION; TAXOL; GENE THERAPY ID METASTATIC BREAST-CANCER; MULTIPLE-DRUG RESISTANCE; EXPRESSION; SUPPORT; TRANSDUCTION; GENE AB We used an animal model system to transplant lethally-irradiated mice with one million marrow cells which had been: (1) collected from 5-fluorouracil (5-FU) treated mice; and (2) transduced with retroviruses containing a multiple drug resistance-1 (MDR-1) gene transcription unit. Following recovery from the transplant, we exposed these mice to doses of taxol ranging from 7 mg/kg to 30 mg/kg, which corresponds to doses of 68 to 268 mg/m(2) in man. The median white blood cell count by 5 days after taxol (expressed as the percentage of the white blood cell count before taxol) was 83% (range 46-100%) in 11 courses of taxol in mice transplanted once with MDR-1 transduced marrow immediately after transplant, whereas the median white blood cell count by 5 days after taxol in mice not transplanted with MDR-1 marrow was 41% in nine courses of taxol (range 11-66%). This difference is statistically different at the P<0.001 level (Wilcoxon test). One million marrow cells from the MDR-1 transplanted mice were harvested and serially transplanted through five additional cohorts of mice, and tested with taxol after each cohort. The white blood cell count (expressed as the percentage of pre-taxol white blood cell count) after each cohort ranged from 94-146% in the 29 mice transplanted with the transduced MDR-1 marrow, which had been through more than one transplant. This is statistically different from the median white blood cell count recovery after taxol in mice which have no human MDR-1 modified marrow (P<0.001). Reverse transcription polymerase chain reaction (RT PCR) analysis showed conclusively that the human MDR-1 cDNA continued to be expressed after four cohorts of transplants, 17 months after the initial transduction and transplant. These data suggest that the vector systems we have used could have modified precursor cells with a capacity for long-term self-renewal and show that the human MDR-1 transcription unit continued to be transcriptionally active with taxol selection in the mouse cells for over 17 months. Thus, such vectors may be of use in protecting hematopoietic cells in patients undergoing taxol treatment from the myelotoxic effects of that therapy. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. UNIV ILLINOIS,COLL MED,CHICAGO,IL 60612. NATL INST HLTH,CELL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA16672, CML PO1 CA49639] NR 18 TC 68 Z9 70 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1995 VL 2 IS 4 BP 279 EP 284 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA RC405 UT WOS:A1995RC40500007 PM 7552988 ER PT J AU BRAVERMAN, JM HUDSON, RR KAPLAN, NL LANGLEY, CH STEPHAN, W AF BRAVERMAN, JM HUDSON, RR KAPLAN, NL LANGLEY, CH STEPHAN, W TI THE HITCHHIKING EFFECT ON THE SITE FREQUENCY-SPECTRUM OF DNA POLYMORPHISMS SO GENETICS LA English DT Article ID DROSOPHILA-ANANASSAE POPULATIONS; MOLECULAR GENETIC-VARIATION; CENTROMERIC REGION; X-CHROMOSOME; MELANOGASTER; RECOMBINATION; NEUTRALITY; MUTATIONS; SIMULANS; LOCUS AB The level of DNA sequence variation is reduced in regions of the Drosophila melanogaster genome where the rate of crossing over per physical distance is also reduced. This observation has been interpreted as support for the simple model of genetic hitchhiking, in which directional selection on rare variants, e.g., newly arising advantageous mutants, sweeps linked neutral alleles to fixation, thus eliminating polymorphisms near the selected site. However, the frequency spectra of segregating sites of several loci from some populations exhibiting reduced levels of nucleotide diversity and reduced numbers of segregating sites did not appear different from what would be expected under a neutral equilibrium model. Specifically, a skew toward an excess of rare sites was not observed in these samples, as measured by Tajima's D. Because this skew was predicted by a simple hitchhiking model, yet it had never been expressed quantitatively and compared directly to DNA polymorphism data, this paper investigates the hitchhiking effect on the site frequency spectrum, as measured by Tajima's D and several other statistics, using a computer simulation model based on the coalescent process and recurrent hitchhiking events. The results presented here demonstrate that under the simple hitchhiking model (1) the expected value of Tajima's D is large and negative (indicating a skew toward rare variants), (2) that Tajima's test has reasonable power to detect a skew in the frequency spectrum for parameters comparable to those from actual data sets, and (3) that the Tajima's Ds observed in several data sets are very unlikely to have been the result of simple hitchhiking. Consequently, the simple hitchhiking model is not a sufficient explanation for the DNA polymorphism at those loci exhibiting a decreased number of segregating sites yet not exhibiting a skew in the frequency spectrum. C1 UNIV CALIF DAVIS, EVOLUT & ECOL SECT, DAVIS, CA 95616 USA. UNIV CALIF IRVINE, DEPT ECOL & EVOLUTIONARY BIOL, IRVINE, CA 92717 USA. NIEHS, STAT & BIOMATH BRANCH, RES TRIANGLE PK, NC 27709 USA. UNIV MARYLAND, DEPT ZOOL, COLLEGE PK, MD 20742 USA. RP BRAVERMAN, JM (reprint author), UNIV CALIF DAVIS, CTR POPULAT BIOL, DAVIS, CA 95616 USA. NR 37 TC 381 Z9 384 U1 2 U2 20 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1995 VL 140 IS 2 BP 783 EP 796 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA RA366 UT WOS:A1995RA36600031 PM 7498754 ER PT J AU BUTLER, RN COLLINS, KS MEIER, DE MULLER, CF PINN, VW AF BUTLER, RN COLLINS, KS MEIER, DE MULLER, CF PINN, VW TI OLDER WOMENS HEALTH - CLINICAL CARE IN THE POSTMENOPAUSAL YEARS SO GERIATRICS LA English DT Discussion ID FRACTURES AB Prevention of late-life disability is an important goal in managing th health care of older women. Hormone replacement therapy and regular exercise can protect against osteoporosis and heart disease. Dietary measures can control weight and prevent diabetes. Adequate calcium and vitamin D intake help protect bones from fractures. Mammography and Pap smears are proven screens for early cancer detection. Depression is not unusual in older women, but it is often masked by physical symptoms. Physicians can help women at risk for caregiver burnout by providing referrals and information on community resources. Use of other health professionals, as well as patient education videos and printed materials, can help physicians provide comprehensive care within the time limits of office practice. C1 INT LONGEV CTR,NEW YORK,NY. COMMONWEALTH FUND,NEW YORK,NY. NIH,OFF WOMENS HLTH,BETHESDA,MD 20892. RP BUTLER, RN (reprint author), MT SINAI MED CTR,HENRY L SCHWARTZ DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUN PY 1995 VL 50 IS 6 BP 33 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA RB682 UT WOS:A1995RB68200007 PM 7768464 ER PT J AU MOSS, NE AF MOSS, NE TI WHY ARE SOME PEOPLE HEALTHY AND OTHERS NOT - THE DETERMINANTS OF HEALTH OF POPULATIONS - EVANS,RG, BARER,ML, MARMOR,TR SO HEALTH AFFAIRS LA English DT Book Review RP MOSS, NE (reprint author), NIH,DEMOG & POPULAT EPIDEMIOL BEHAV & SOCIAL RES PROG,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SUM PY 1995 VL 14 IS 2 BP 318 EP 321 DI 10.1377/hlthaff.14.2.318 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA RK804 UT WOS:A1995RK80400033 ER PT J AU BORDIGNON, C BONINI, C VERZELETTI, S NOBILI, N MAGGIONI, D TRAVERSARI, C GIAVAZZI, R SERVIDA, P ZAPPONE, E BENAZZI, E BERNARDI, M PORTA, F FERRARI, G MAVILIO, F ROSSINI, S BLAESE, RM CANDOTTI, F AF BORDIGNON, C BONINI, C VERZELETTI, S NOBILI, N MAGGIONI, D TRAVERSARI, C GIAVAZZI, R SERVIDA, P ZAPPONE, E BENAZZI, E BERNARDI, M PORTA, F FERRARI, G MAVILIO, F ROSSINI, S BLAESE, RM CANDOTTI, F TI TRANSFER OF THE HSV-TK GENE INTO DONOR PERIPHERAL-BLOOD LYMPHOCYTES FOR IN-VIVO MODULATION OF DONOR ANTITUMOR IMMUNITY AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION SO HUMAN GENE THERAPY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; EPSTEIN-BARR-VIRUS; CHRONIC MYELOID-LEUKEMIA; VERSUS-HOST DISEASE; LEUKOCYTE INFUSIONS; CHRONIC PHASE; RELAPSE; INTERFERON; THERAPY; IMMUNOTHERAPY AB The infusion of donor lymphocytes after allogeneic bone; marrow transplantation is a promising therapeutic tool for achieving a graft versus leukemia (GvL) effect in case of leukemic relapse (1-7), and for the treatment of other complications related to the severe immunosuppressive status of transplanted patients, such as Epstein Barr virus-induced lymphoproliferative disorders (EBV-BLPD) (8) or reactivation of CMV infection (9). Although the delay in the administration of T lymphocytes is expected to reduce the risk of severe GVHD, this risk is still present at higher doses of donor T-cells. The transfer of a suicide gene into donor lymphocytes could allow the in vivo selective elimination of cells responsible for severe GvHD. Additionally, under appropriate conditions, it may allow in vivo modulation of donor anti-tumor responses, and to separate GvL from GvHD. Finally, crucial questions concerning survival and function of donor lymphocytes could be answered by their gene marking. Previous studies documented that T lymphocytes are suitable targets for gene transfer through retroviral vectors (10,11). This protocol has been designed to evaluate in the contest of allogeneic BMT: 1-the safety of increasing doses of donor lymphocytes transduced with a suicide retroviral vector; 2--the efficacy in terms of survival and immunologic potential of donor lymphocytes after in vitro activation, gene transduction, and immunoselection; 3-the possibility of in vivo down regulation of GvHD by the administration of ganciclovir to patients treated by tk-transduced donor lymphocytes. Patients will be enrolled in three groups: A-patients in complete remission after a T depleted allo-BMT, in order to prevent disease relapse; B-patients with relapse of hematologic malignancies after allo-BMT, in order to achieve a GvL effect; C-patients with an EBV-BLPD after allo-BMT, in order to provide donor EBV-specific T-cells. For this purpose, donor peripheral blood lymphocytes (PBL), will be transduced with a suicide retroviral vector containing two genes: the first coding for the thymidine kinase of the herpes simplex virus (HSV-tk) and the second coding for the low affinity receptor for NGF(12) truncated of its intracellular domain (Delta NGFR). The HSV-tk confers ganciclovir sensitivity (13), thus allowing in vivo selective downregulation of all transduced allogeneic cells in case of severe GvHD. The Delta NGFR will be used as a cell surface marker allowing rapid in vitro immunoselection of transduced cells, and ex vivo detection and characterization of the transduced cells after infusion. C1 IST SCI HS RAFFAELE,BONE MARROW TRANSPLANTAT & GENE THERAPY PROGRAM,I-20132 MILAN,ITALY. IST RIC FARMACOL MARIO NEGRI,BERGAMO,ITALY. UNIV BRESCIA,BRESCIA,ITALY. NCI,CELLULAR IMMUNOL SECT,BETHESDA,MD. RI bonini, chiara/I-9202-2012; Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; BONINI, Maria Chiara/0000-0002-0772-1674; Mavilio, Fulvio/0000-0003-0459-4320 NR 42 TC 105 Z9 111 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 1995 VL 6 IS 6 BP 813 EP 819 DI 10.1089/hum.1995.6.6-813 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA RD994 UT WOS:A1995RD99400012 PM 7548281 ER PT J AU GUAN, XY MELTZER, PS BURGESS, AC TRENT, JM AF GUAN, XY MELTZER, PS BURGESS, AC TRENT, JM TI COVERAGE OF CHROMOSOME-6 BY CHROMOSOME MICRODISSECTION - GENERATION OF 14 SUBREGION-SPECIFIC PROBES SO HUMAN GENETICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; HUMAN GENOME; RAPID GENERATION; DNA LIBRARIES; CLONES; REGION; AMPLIFICATION; TRANSLOCATIONS; CONSTRUCTION; CLONING AB Human chromosome 6 has been subdivided by chromosome microdissection into 14 unique regions. Following microdissection, polymerase chain reaction (PCR) amplification of dissected DNA was performed using a universal primer to generate subregion-specific probes that provided complete coverage of chromosome 6. All 16 microdissections have been regionally assigned along chromosome 6 by fluorescence in situ hybridization (FISH) using biotin-labeled dissected DNA hybridized to G-banded normal metaphase chromosomes. These probes can be used as region-specific paints to generate unique ''bar codes'' and for analysis of chromosome alterations involving chromosome 6 that are unidentifiable by conventional banding analysis. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 17 TC 25 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1995 VL 95 IS 6 BP 637 EP 640 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA QZ629 UT WOS:A1995QZ62900004 PM 7789947 ER PT J AU SUNADA, Y BERNIER, SM UTANI, A YAMADA, Y CAMPBELL, KP AF SUNADA, Y BERNIER, SM UTANI, A YAMADA, Y CAMPBELL, KP TI IDENTIFICATION OF A NOVEL MUTANT TRANSCRIPT OF LAMININ ALPHA-2 CHAIN GENE RESPONSIBLE FOR MUSCULAR-DYSTROPHY AND DYSMYELINATION IN DY(2J) MICE SO HUMAN MOLECULAR GENETICS LA English DT Article ID BASEMENT-MEMBRANES; PROTEINS; MEROSIN; GLYCOPROTEIN; DEFICIENCY; CELLS; NERVE AB Murine dystrophia muscularis-2J (dy(2J)) is an autosomal recessive disorder characterized by muscular dystrophy and dysmyelination of peripheral nerve, Biochemical characterization of dy(2J) mice revealed the expression of a mutant laminin alpha 2 chain with a smaller molecular weight in the basal lamina of striated muscle and peripheral nerve, DNA sequencing of the alpha 2 chain cDNA amplified by RT-PCR from dy(2J) mice identified a novel and predominant transcript with a 171 base in-frame deletion. We also confirmed an underlying splice donor site mutation in the alpha 2 chain gene of the dy(2J) mouse, Translation of this variant transcript would result in the expression of a truncated alpha 2 chain having a 57 amino acid deletion (residues 34-90) and a substitution of Gln91Glu in the N-terminal domain VI, which is presumed to be involved in self-aggregation of laminin heterotrimers. Thus, the mutant alpha 2 chain could disrupt the formation of the laminin network and lead to muscle cell degeneration. Our results provide a molecular basis of muscular dystrophy and dysmyelination of peripheral nerve. C1 UNIV IOWA,COLL MED,HOWARD HUGHES MED INST,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 32 TC 133 Z9 133 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1995 VL 4 IS 6 BP 1055 EP 1061 DI 10.1093/hmg/4.6.1055 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RC123 UT WOS:A1995RC12300012 PM 7655459 ER PT J AU STEWART, DM KURMAN, CC NELSON, DL AF STEWART, DM KURMAN, CC NELSON, DL TI PRODUCTION OF MONOCLONAL-ANTIBODIES TO BRUTONS TYROSINE KINASE SO HYBRIDOMA LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; SIGNALING PROTEINS; ESCHERICHIA-COLI; DOMAIN; EXPRESSION AB Bruton's X-linked agammaglobulinemia is caused by mutations in a cytoplasmic protein tyrosine kinase termed Bruton's tyrosine kinase (BTK). The protein is expressed in all members of the B cell lineage and is critical for B cell development, The protein consists of several modules, including a pleckstrin homology domain and the Src homology domains SH1, SH2, and SH3. We report here the production of monoclonal antibodies against the pleckstrin homology domain of human BTK. The antibody was produced by immunizing mice with a FLAG-BTK fusion protein, Hybridoma supernatants were screened by ELISA using a GST-BTK fusion protein as the antigen. Selected monoclonal antibodies recognize denatured BTK on Western blots of peripheral blood mononuclear cell lysates. Mouse BTK protein is also detected. These antibodies should be useful in assessing patients with immune deficiency, as well as in studying normal B cell development. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NR 17 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 243 EP 246 DI 10.1089/hyb.1995.14.243 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500005 PM 7590786 ER PT J AU NELSON, DL AF NELSON, DL TI MONOCLONAL-ANTIBODIES - 8E5A10, ANTI-BTK SO HYBRIDOMA LA English DT Note RP NELSON, DL (reprint author), NCI,METAB BRANCH,BLDG 10,RM 4N-115,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1995 VL 14 IS 3 BP 311 EP 311 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RF575 UT WOS:A1995RF57500033 ER PT J AU COOK, NR CUTLER, JA HENNEKENS, CH AF COOK, NR CUTLER, JA HENNEKENS, CH TI AN UNEXPECTED RESULT FOR SODIUM - CAUSAL OR CASUAL SO HYPERTENSION LA English DT Editorial Material DE CARDIOVASCULAR DISEASE; HYPERTENSION, SODIUM-DEPENDENT; BLOOD PRESSURE; SODIUM; MYOCARDIAL INFARCTION ID LOWER BLOOD-PRESSURE; SALT REDUCTION; OBSERVATIONAL DATA; HEART-DISEASE; HYPERTENSION; POPULATIONS; RISK C1 NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. RP COOK, NR (reprint author), BRIGHAM & WOMENS HOSP, DIV PREVENT MED, 900 COMMONWEALTH AVE E, BOSTON, MA 02215 USA. NR 18 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1995 VL 25 IS 6 BP 1153 EP 1154 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RB882 UT WOS:A1995RB88200006 PM 7768555 ER PT J AU VAZIRI, SM LARSON, MG LAUER, MS BENJAMIN, EJ LEVY, D AF VAZIRI, SM LARSON, MG LAUER, MS BENJAMIN, EJ LEVY, D TI INFLUENCE OF BLOOD-PRESSURE ON LEFT ATRIAL SIZE - THE FRAMINGHAM HEART-STUDY SO HYPERTENSION LA English DT Article DE ATRIAL FUNCTION, LEFT; HYPERTENSION, ESSENTIAL; EPIDEMIOLOGY; ECHOCARDIOGRAPHY ID LEFT-VENTRICULAR MASS; ECHOCARDIOGRAPHIC MEASUREMENTS; HYPERTENSIVE SUBJECTS; MITRAL-STENOSIS; DISEASE; FIBRILLATION; HYPERTROPHY; ENLARGEMENT; PERFORMANCE; POPULATION AB Increased left atrial size has been identified as a precursor of atrial fibrillation and of stroke once atrial fibrillation is manifest. Conflicting data exist regarding the effect of high blood pressure on left atrial size. Our objective was to evaluate the association of contemporary and long-term measures of blood pressure with echocardiographically determined left atrial size in a large, population-based cohort. The study sample consisted of 1849 male and 2152 female participants of the Framingham Heart Study and Framingham Offspring Study. All analyses were sex specific. In correlation analyses, systolic and pulse pressures were identified as statistically significant determinants of left atrial size after adjustment for age and body mass index, although the magnitudes of these relations were very modest (partial r less than or equal to .10). Multivariable linear regression models showed the relative contributions of the pressure variables to the prediction of left atrial size to be substantially less than those of age and, in particular, body mass index. Furthermore, inclusion of left ventricular mass in these multivariable models eliminated or attenuated the associations of the pressure variables with left atrial size. In logistic analyses, increasing levels of the pressure variables were significantly predictive of left atrial enlargement. Subjects with 8-year average systolic pressure of 140 mm Hg or higher were twice as likely to have left atrial enlargement as those with values Of 110 mm Hg or lower. Overall, in this population-based study sample, increased levels of systolic and pulse pressures (but not diastolic or mean arterial pressures) were significantly associated with increased left atrial size. However the magnitude of these associations was quite modest, particularly after controlling for age and body mass index. C1 FRAMINGTON HEART STUDY,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. CLEVELAND CLIN,DIV CARDIOL,CLEVELAND,OH 44106. BOSTON CITY HOSP,CARDIOL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV PREVENT MED & EPIDEMIOL,BOSTON,MA 02118. NHLBI,BETHESDA,MD 20892. RI Lauer, Michael/L-9656-2013; OI Lauer, Michael/0000-0002-9217-8177; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 NR 42 TC 150 Z9 158 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1995 VL 25 IS 6 BP 1155 EP 1160 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RB882 UT WOS:A1995RB88200007 PM 7768556 ER PT J AU ABASSI, ZA KOTOB, S GOLOMB, E PIERUZZI, F KEISER, HR AF ABASSI, ZA KOTOB, S GOLOMB, E PIERUZZI, F KEISER, HR TI PULMONARY AND RENAL NEUTRAL ENDOPEPTIDASE EC-3.4.24.11 IN RATS WITH EXPERIMENTAL HEART-FAILURE SO HYPERTENSION LA English DT Article DE MEMBRANE METALLOENDOPEPTIDASE; HEART FAILURE, CONGESTIVE; KIDNEY; LUNG; NATRIURESIS ID ATRIAL-NATRIURETIC-PEPTIDE; INHIBITION; SODIUM; ENDOTHELIN; METABOLISM; BALANCE; KIDNEY; DOGS; GENE; ANF AB Congestive heart failure is characterized by avid sodium retention and a blunted renal response to exogenous and endogenous atrial natriuretic peptide. Inhibition of neutral endopeptidase EC 3.4.24.11, the main enzyme that degrades natriuretic peptides, produces a natriuretic response in different models of congestive heart failure. This raises the possibility that an increase in either the expression or activity of neutral endopeptidase is responsible for these phenomena. In the present study, we examined (1) the renal effects of SQ-28,603, a neutral endopeptidase inhibitor, in rats with moderate and severe congestive heart failure induced by an aortocaval fistula compared with sham controls, and (2) neutral endopeptidase expression and activity in the lungs and kidneys of these rats. Infusion of SQ-28,603 (40 mg/kg IV) induced a significant natriuretic response in normal rats and rats with moderate congestive heart failure. This response was blunted in rats with severe congestive heart failure. Surprisingly, renal neutral endopeptidase mRNA levels, assessed by quantitative reverse transcriptase-polymerase chain reaction; protein levels, assessed by Western blotting; and activity, assessed by gelatin gels, were comparable in all groups. Pulmonary neutral endopeptidase mRNA levels decreased by 45% in rats with severe congestive heart failure but not in rats with mild congestive heart failure. In addition, pulmonary neutral endopeptidase immunoreactivity levels and activity were significantly decreased in congestive heart failure in correlation with the severity of the disorder. We conclude that an increase in neutral endopeptidase expression or activity does not occur in rats with congestive heart failure, and therefore, an upregulation of neutral endopeptidase is unlikely to account for the blunted natriuretic response to the atrial natriuretic peptide and the positive sodium balance in congestive heart failure. C1 UNIV MARYLAND,DEPT MICROBIOL,COLLEGE PK,MD 20742. UNIV MILAN,OSPED MAGGIORE,CTR FISIOL CLIN & IPERTENS,MILAN,ITALY. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,BETHESDA,MD 20892, USA. NR 44 TC 11 Z9 11 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1995 VL 25 IS 6 BP 1178 EP 1184 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RB882 UT WOS:A1995RB88200011 PM 7768560 ER PT J AU HWANG, YS DAS, R SALTZ, JH AF HWANG, YS DAS, R SALTZ, JH TI PARALLELIZING MOLECULAR-DYNAMICS PROGRAMS FOR DISTRIBUTED-MEMORY MACHINES SO IEEE COMPUTATIONAL SCIENCE & ENGINEERING LA English DT Article ID ENERGY AB Using a data-parallel strategy to parallelize molecular dynamics programs makes it possible to simulate very large molecules on large numbers of processors. Applying an appropriate combination of data partitioning and iteration distribution algorithms not only optimizes communication overheads but also achieves good load balance, and hence good performance. C1 NIH,BETHESDA,MD 20892. RP HWANG, YS (reprint author), UNIV MARYLAND,HIGH PERFORMANCE SYST SOFTWARE LAB,COLLEGE PK,MD 20742, USA. NR 10 TC 30 Z9 30 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 SN 1070-9924 J9 IEEE COMPUT SCI ENG JI IEEE Comput. Sci. Eng. PD SUM PY 1995 VL 2 IS 2 BP 18 EP 29 DI 10.1109/99.388949 PG 12 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Mathematics, Applied SC Computer Science; Engineering; Mathematics GA RE185 UT WOS:A1995RE18500008 ER PT J AU VRHEL, MJ TRUSSELL, HJ AF VRHEL, MJ TRUSSELL, HJ TI OPTIMAL COLOR FILTERS IN THE PRESENCE OF NOISE SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article ID FUNDAMENTAL METAMERS; REPRODUCTION; MIXTURE; IMAGES AB In this paper, the effect of noise on the number of effective channels (color filters) used to record a color image is investigated, Transmittances of color filters are calculated that minimize the mean square error that occurs when estimating, from the recorded data, the colors in the image under a collection of viewing illuminants. Since the results indicate that a significant improvement in color correction accuracy is achieved by using four channels, there is good reason to consider using four-tuples for representation of colorimetric information. C1 N CAROLINA STATE UNIV,DEPT ELECT & COMP ENGN,RALEIGH,NC 27695. RP VRHEL, MJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 24 TC 44 Z9 44 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD JUN PY 1995 VL 4 IS 6 BP 814 EP 823 DI 10.1109/83.388082 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA RA645 UT WOS:A1995RA64500009 PM 18290030 ER PT J AU BISWAS, P SMITH, CA GOLETTI, D HARDY, EC JACKSON, RW FAUCI, AS AF BISWAS, P SMITH, CA GOLETTI, D HARDY, EC JACKSON, RW FAUCI, AS TI CROSS-LINKING OF CD30 INDUCES HIV EXPRESSION IN CHRONICALLY INFECTED T-CELLS SO IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW TRANSPLANTATION; LONG TERMINAL REPEAT; STERNBERG-REED CELLS; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; HODGKINS-DISEASE; FACTOR RECEPTOR; KAPPA-B AB CD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2, which is chronically infected with human immunodeficiency virus type-1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-specific monoclonal antibody, which mimics the described biological activities of the CD30 ligand (CD30L), results in HIV expression. CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta. Furthermore, cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription. Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF. This mechanism may be important in the activation of HIV expression from latently infected CD4(+) T cells, especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand Interactions. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. OI Goletti, Delia/0000-0001-8360-4376 NR 58 TC 72 Z9 72 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 1995 VL 2 IS 6 BP 587 EP 596 PG 10 WC Immunology SC Immunology GA RE538 UT WOS:A1995RE53800004 PM 7540942 ER PT J AU SMYTH, MJ HULETT, MD THIA, KYT YOUNG, HA SAYERS, TJ CARTER, CRD TRAPANI, JA AF SMYTH, MJ HULETT, MD THIA, KYT YOUNG, HA SAYERS, TJ CARTER, CRD TRAPANI, JA TI CLONING AND CHARACTERIZATION OF A NOVEL NK CELL-SPECIFIC SERINE-PROTEASE GENE AND ITS FUNCTIONAL 5'-FLANKING SEQUENCES SO IMMUNOGENETICS LA English DT Article ID NATURAL-KILLER-CELLS; CYTO-TOXIC LYMPHOCYTES; GENOMIC ORGANIZATION; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; MESSENGER-RNAS; CATHEPSIN-G; BEIGE MICE; GRANZYME-A AB Rat natural killer cell Met-ase-1 (RNK-Met-1) is a 30000 M(r) serine protease (granzyme) found in the cytolytic granules of CD3- large granular lymphocytes (LGL) with natural killer (NK) activity. To characterize the genomic sequences responsible for the CD3- LGL-restricted expression of this gene, we screened a rat genomic library with RNK-Met-1 cDNA, and obtained bacteriophage clones that contained the RNK-Met-1 gene. The RNK-Met-1 gene comprises 5 exons and spans approximately 5.2 kilobases (kb), exhibiting a similar structural organization to a class of CTL-serine proteases with protease catalytic residues encoded near the borders of exons 2, 3, and 5. The 5'-flanking region of the RNK-Met-1 gene contains a number of putative promoter and enhancer regulatory elements and shares several regions of homology with the 5'-flanking region of the mouse perforin gene. We have prepared nested deletions from approximately 3.3 kb of the 5'-flanking region of the RNK-Met-1 gene, and inserted these upstream of the chloramphenicol acetyltransferase (CAT) reporter gene. These 5'-flanking RNK-Met-1-CAT constructs were transiently transfected into rat LGL leukemia, T-lymphoma, and basophilic leukemia cell lines. The transcriptional activity of the RNK-Met-1 5'-flanking region was strong, restricted to the RNK-16 LGL leukemia and controlled by several positive cis-acting regions spread over at least 3.3 kb. The longest and most active 5'-flanking region (-3341 to -33) was also used to drive specific expression of beta-galactosidase in RNK-16. These data are consistent with the NK cell-specific expression of RNK-Met-1 and suggest the potential utility of this gene promoter in the development of transgene models of NK cell biology in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP SMYTH, MJ (reprint author), AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,HEIDELBERG,VIC 3084,AUSTRALIA. RI Hulett, Mark/C-4160-2012; Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 67 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUN PY 1995 VL 42 IS 2 BP 101 EP 111 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA RF710 UT WOS:A1995RF71000004 PM 7607701 ER PT J AU GOLDENBERG, DM LARSON, SM REISFELD, RA SCHLOM, J AF GOLDENBERG, DM LARSON, SM REISFELD, RA SCHLOM, J TI TARGETING CANCER WITH RADIOLABELED ANTIBODIES SO IMMUNOLOGY TODAY LA English DT Editorial Material AB A recent conference* focused on the advances, challenges and prospects of radioimmunodetection (RAID) and radioimmunotherapy (RAIT) of cancer. Emphasis was given to the underlying sciences of radiochemistry as well as its clinical and experimental applications. C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. NCI,BETHESDA,MD 20852. RP GOLDENBERG, DM (reprint author), GARDEN STATE CANC CTR,CTR MOLEC MED & IMMUNOL,NEWARK,NJ 07103, USA. FU NCI NIH HHS [R13 CA 63744] NR 0 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUN PY 1995 VL 16 IS 6 BP 261 EP 264 DI 10.1016/0167-5699(95)80177-4 PG 4 WC Immunology SC Immunology GA RB614 UT WOS:A1995RB61400003 PM 7662094 ER PT J AU DIRAMI, G PAPADOPOULOS, V KLEINMAN, HK DEFREESE, DC MUSTO, NA DYM, M AF DIRAMI, G PAPADOPOULOS, V KLEINMAN, HK DEFREESE, DC MUSTO, NA DYM, M TI IDENTIFICATION OF TRANSFERRIN AND INHIBIN-LIKE PROTEINS IN MATRIGEL SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Letter ID RAT SERTOLI CELLS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; VECTORIAL SECRETION; GROWTH; DIFFERENTIATION; PRECURSORS; COMPONENTS; INVITRO; CULTURE C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIDR,BETHESDA,MD 20892. OI Papadopoulos, Vassilios/0000-0002-1183-8568 NR 23 TC 5 Z9 5 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 1995 VL 31 IS 6 BP 409 EP 411 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA RG483 UT WOS:A1995RG48300001 ER PT J AU MARGOLIS, L BAIBAKOV, B COLLIN, C SIMON, SA AF MARGOLIS, L BAIBAKOV, B COLLIN, C SIMON, SA TI DYE-COUPLING IN 3-DIMENSIONAL HISTOCULTURE OF RAT LINGUAL FRENULUM SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE GAP JUNCTIONS; TONGUE; STRATIFIED EPITHELIUM; TISSUE CULTURE ID FREEZE-FRACTURE; HUMAN EPIDERMIS; GAP-JUNCTIONS; CELLS; GROWTH; DIFFERENTIATION; COMMUNICATION; EPITHELIUM; PAPILLAE; TUMORS AB A three-dimensional histoculture of wet stratified squamous epithelium of rat lingual frenulum was cultured on a liquid-air interface. The tissue retained its morphology for many days in culture. During this period the vast majority of the epithelial cells remained viable and exhibited dye (lucifer yellow) coupling in all living epithelial strata. Dye coupling was determined using two methods: the conventional intracellular injection method, and a new method-''cut-loading.'' In the cut-loading method, an incision is made in the epithelium in the presence of dye, and intracellular diffusion of dye throughout the epithelium was measured using confocal microscopy. The basolateral surface of the lingual frenulum also acted as a substrate for neuroblastoma cells to grow without exogenously added trophic factors. These neuroblastoma cells grow neurites that establish contacts with epithelial cells. This preparation can serve as a model for investigating interactions among epithelial cells and between nerves and epithelial cells. C1 MOSCOW MV LOMONOSOV STATE UNIV,BELOZORSKY INST PHYSICOCHEM BIOL,MOSCOW,RUSSIA. DUKE UNIV,DEPT NEUROBIOL,DURHAM,NC 27710. DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC 27710. RP MARGOLIS, L (reprint author), NIH,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 10D14,BETHESDA,MD 20892, USA. FU NIDCD NIH HHS [DC 0165] NR 27 TC 0 Z9 0 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 1995 VL 31 IS 6 BP 456 EP 461 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA RG483 UT WOS:A1995RG48300012 PM 8589889 ER EF