FN Thomson Reuters Web of Science™ VR 1.0 PT J AU JONES, TH DEVRIES, PJ ESCOUBAS, P AF JONES, TH DEVRIES, PJ ESCOUBAS, P TI CHEMISTRY OF VENOM ALKALOIDS IN THE ANT MEGALOMYRMEX-FORELI (MYRMICINAE) FROM COSTA-RICA SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE MEGALOMYRMEX; HYMENOPTERA; MYRMICINAE; VENOM; ALKALOIDS; ANTS; PYRROLINES; ALARM BEHAVIOR; STRIDULATION; TOXICITY ID ADULT MOTH; MONOMORIUM; SOLENOPSIS; ISOPTERA; DEFENSE; ENZYMES AB Chemical analysis of the venom of the myrmicine ant Megalomyrmex foreli from Costa Rica revealed the presence of four major alkaloidal components. Two of these, 2-butyl-5-(E, 1-heptenyl)-5-pyrroline (3) and 2-butyl-5-(E, E, 1,3-heptadienyl)-5-pyrroline (4), constitute a new functional class of ant venom alkaloids, whose structures were assigned from their spectral and chemical behavior and unambiguous syntheses. The function of these compounds is suggested by field observations of the behavior of M. foreli, its sting morphology, and the relative toxicity of 3 and 4 against termite workers. C1 UNIV TEXAS,DEPT ZOOL,AUSTIN,TX 78712. RES DEV CORP JAPAN,PLANT ECOCHEM PROJECT,ENIWA 06113,JAPAN. RP JONES, TH (reprint author), NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892, USA. NR 29 TC 18 Z9 18 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD DEC PY 1991 VL 17 IS 12 BP 2507 EP 2518 DI 10.1007/BF00994598 PG 12 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA GW893 UT WOS:A1991GW89300013 PM 24258643 ER PT J AU TAYLOR, SI CAMA, A ACCILI, D BARBETTI, F IMANO, E KADOWAKI, H KADOWAKI, T AF TAYLOR, SI CAMA, A ACCILI, D BARBETTI, F IMANO, E KADOWAKI, H KADOWAKI, T TI GENETIC-BASIS OF ENDOCRINE DISEASE .1. MOLECULAR-GENETICS OF INSULIN RESISTANT DIABETES-MELLITUS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYROSINE KINASE DOMAIN; RECEPTOR GENE; IMPAIRS TRANSPORT; MUTANT ALLELES; MUTATION; DELETION; SEQUENCE; PATIENT; BINDING; NIDDM C1 UNIV TOKYO, FAC MED, DEPT INTERNAL MED 3, TOKYO 113, JAPAN. ASAHI LIFE FDN, INST DIABET CARE & RES, TOKYO, JAPAN. OSAKA UNIV, DEPT INTERNAL MED 1, OSAKA, JAPAN. RP TAYLOR, SI (reprint author), NIDDKD, DIABET BRANCH, BLDG 10, ROOM 85-243, BETHESDA, MD USA. NR 31 TC 53 Z9 54 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1991 VL 73 IS 6 BP 1158 EP 1163 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GW879 UT WOS:A1991GW87900002 PM 1955495 ER PT J AU DEMITRACK, MA DALE, JK STRAUS, SE LAUE, L LISTWAK, SJ KRUESI, MJP CHROUSOS, GP GOLD, PW AF DEMITRACK, MA DALE, JK STRAUS, SE LAUE, L LISTWAK, SJ KRUESI, MJP CHROUSOS, GP GOLD, PW TI EVIDENCE FOR IMPAIRED ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN PATIENTS WITH CHRONIC FATIGUE SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; EPSTEIN-BARR VIRUS; SECRETION INVITRO; CUSHINGS-SYNDROME; STIMULATION TEST; PLASMA-CORTISOL; NERVOUS-SYSTEM; LEWIS RATS; INFECTION; PERSISTENT AB Chronic fatigue syndrome is characterized by persistent or relapsing debilitating fatigue for at least 6 months in the absence of a medical diagnosis that would explain the clinical presentation. Because primary glucocorticoid deficiency states and affective disorders putatively associated with a deficiency of the arousal-producing neuropeptide CRH can be associated with similar symptoms, we report here a study of the functional integrity of the various components of the hypothalamic-pituitary-adrenal axis in patients meeting research case criteria for chronic fatigue syndrome. Thirty patients and 72 normal volunteers were studied. Basal activity of the hypothalamic-pituitary-adrenal axis was estimated by determinations of 24-h urinary free cortisol-excretion, evening basal plasma total and free cortisol concentrations, and the cortisol binding globulin-binding capacity. The adrenal cortex was evaluated indirectly by cortisol responses during ovine CRH (oCRH) stimulation testing and directly by cortisol responses to graded submaximal doses of ACTH. Plasma ACTH and cortisol responses to oCRH were employed as a direct measure of the functional integrity of the pituitary corticotroph cell. Central CRH secretion was assessed by measuring its level in cerebrospinal fluid. Compared to normal subjects, patients demonstrated significantly reduced basal evening glucocorticoid levels (89.0 +/- 8.7 vs. 148.4 +/- 20.3 nmol/L; P < 0.01) and low 24-h urinary free cortisol excretion (122.7 +/- 8.9 vs. 203.1 +/- 10.7 nmol/24 h; P < 0.0002), but elevated basal evening ACTH concentrations. There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response [F(3.26, 65.16) = 5.50; P = 0.0015). Patients showed attenuated net integrated ACTH responses to oCRH (128.0 +/- 26.4 vs. 225.4 +/- 34.5 pmol/L.min, P < 0.04). Cerebrospinal fluid CRH levels in patients were no different from control values (8.4 +/- 0.6 vs. 7.7 +/- 0.5 pmol/L; P = NS). Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated. Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CHILD PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NIAID, MED VIROL SECT, CLIN INVEST LAB, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Demitrack, Mark/I-7697-2013 NR 54 TC 525 Z9 528 U1 3 U2 13 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1991 VL 73 IS 6 BP 1224 EP 1234 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GW879 UT WOS:A1991GW87900012 PM 1659582 ER PT J AU WEHR, TA AF WEHR, TA TI THE DURATIONS OF HUMAN MELATONIN SECRETION AND SLEEP RESPOND TO CHANGES IN DAYLENGTH (PHOTOPERIOD) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CIRCADIAN PACEMAKERS; FUNCTIONAL-ANALYSIS; NOCTURNAL RODENTS; RHYTHM; PLASMA; WINTER; RAT AB Seasonal changes in daylength (photoperiod) modify the duration of nocturnal melatonin (MT) secretion in many vertebrates. In some cases the changes in MT act as chemical signals that trigger photoperiodic induction of breeding and other seasonal phenomena. It is unclear whether, and to what extent changes in daylength modify the duration of human MT secretion. To address this question, I investigated whether the duration of human MT secretion could be altered by artificial photoperiods. I exposed eight healthy volunteers to a conventional "summer" photoperiod of 16 h light and 8 h darkness for 1 week and to a "winter" photoperiod of 10 h light and 14 h darkness for 4 weeks. As occurs in animals, the duration of nocturnal MT secretion in human beings was longer after exposure to the short photoperiod (12.5 +/- 1.8 vs. 10.3 +/- 0.8 h, t = 3.778, P < 0.01). The duration of the sleep-phase (recorded by electroencephalogram) was also longer (11.0 +/- 0.8 vs. 7.7 +/- 0.2 h, t = 11.754, P < 0.001). Whether such changes would lead to significant seasonal changes in human physiology and behavior under natural lighting conditions may be worthy of further investigation. RP WEHR, TA (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH, ROOM 4S-239, BLDG 10, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 18 TC 190 Z9 191 U1 1 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1991 VL 73 IS 6 BP 1276 EP 1280 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GW879 UT WOS:A1991GW87900019 PM 1955509 ER PT J AU FEUILLAN, PP JONES, J OERTER, KE MANASCO, PK CUTLER, GB AF FEUILLAN, PP JONES, J OERTER, KE MANASCO, PK CUTLER, GB TI LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH)-INDEPENDENT PRECOCIOUS PUBERTY UNRESPONSIVE TO LHRH AGONIST THERAPY IN 2 GIRLS LACKING FEATURES OF THE MCCUNE-ALBRIGHT SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID OVARIAN-FUNCTION; RADIOIMMUNOASSAY; CHILDREN; ANALOG; CYSTS AB Two girls with precocious puberty (chronological age, 1 and 4 yr; bone age, 3 and 6 yr, respectively) were initially given the diagnosis of idiopathic, central precocious puberty and treated with the LHRH agonist deslorelin (D-Trp6-Pro9-NEt-LHRH) for 5 yr. Unlike other girls with central precocious puberty, both had persistently elevated rates of growth and bone maturation, and both menstruated during therapy. One girl had episodic ovarian enlargement and markedly elevated serum estradiol levels due to recurrent unilateral ovarian cysts. Although the bone and skin manifestations of McCune-Albright syndrome were absent, we hypothesize that the underlying defect of McCune-Albright syndrome was expressed in the ovaries, but not in the skin or bones, of these two girls. One of these girls appeared to benefit from the aromatase inhibitor testolactone, which is effective in suppressing precocious puberty in girls with the McCune-Albright syndrome. RP FEUILLAN, PP (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 20 TC 14 Z9 15 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1991 VL 73 IS 6 BP 1370 EP 1373 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GW879 UT WOS:A1991GW87900033 PM 1955519 ER PT J AU HAMOSH, A TRAPNELL, BC ZEITLIN, PL MONTROSERAFIZADEH, C ROSENSTEIN, BJ CRYSTAL, RG CUTTING, GR AF HAMOSH, A TRAPNELL, BC ZEITLIN, PL MONTROSERAFIZADEH, C ROSENSTEIN, BJ CRYSTAL, RG CUTTING, GR TI SEVERE DEFICIENCY OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR MESSENGER-RNA CARRYING NONSENSE MUTATIONS R553X AND W1316X IN RESPIRATORY EPITHELIAL-CELLS OF PATIENTS WITH CYSTIC-FIBROSIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ALLELE-SPECIFIC OLIGONUCLEOTIDES; GENOTYPE; PHENOTYPE; POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION ID STOP CODON; GENE; IDENTIFICATION; DNA; TRANSPORT; RECEPTOR; REGIONS; FAMILY; ALLELE; EXON AB Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two African-American patients with nonsense mutations in each CF gene and severe pancreatic disease, but mild pulmonary disease. In order to examine the effect of these nonsense mutations on CF gene expression, bronchial and nasal epithelial cells were obtained from one of these patients (no. 246), a compound heterozygote for nonsense mutations R553X and W1316X; a healthy normal individual; a patient (no. 528) homozygous for the common CF mutation (DELTA-F508); and a CF patient (no. 272) who carries the R553X mutation and a missense mutation, S549N. When mRNA from bronchial cells of the normal individual, the DELTA-F508 homozygote, and the S549N/R553X compound heterozygote was reverse transcribed and amplified by polymerase chain reaction using primers derived from the CF gene, DNA fragments of the predicted size were observed. However, patient no. 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) messenger RNA, and therefore should have severely diminished, and possibly absent, CFTR protein. Furthermore, < 2% of the CFTR transcripts in nasal epithelial cells from patient no. 272 (S549N/R553X) were derived from the gene with the nonsense mutation. We conclude that severe reduction in CFTR mRNA causes CF, but can have different consequences in the lung and pancreas. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. RP HAMOSH, A (reprint author), JOHNS HOPKINS UNIV HOSP,CTR MED GENET,BLALOCK 1008,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 39 TC 123 Z9 124 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1991 VL 88 IS 6 BP 1880 EP 1885 DI 10.1172/JCI115510 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GU967 UT WOS:A1991GU96700012 PM 1721624 ER PT J AU GUPTA, AK KIRCHNER, KA NICHOLSON, R ADAMS, JG SCHECHTER, AN NOGUCHI, CT STEINBERG, MH AF GUPTA, AK KIRCHNER, KA NICHOLSON, R ADAMS, JG SCHECHTER, AN NOGUCHI, CT STEINBERG, MH TI EFFECTS OF ALPHA-THALASSEMIA AND SICKLE POLYMERIZATION TENDENCY ON THE URINE-CONCENTRATING DEFECT OF INDIVIDUALS WITH SICKLE-CELL TRAIT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SICKLE HEMOGLOBIN; RENAL FUNCTION; HYPOSTHENURIA ID GLOBIN GENE; INTRACELLULAR POLYMERIZATION; MOLECULAR-BASIS; HEMOGLOBIN; DISEASE; ERYTHROCYTES; ANEMIA; BLACKS; HETEROGENEITY; DELETION AB A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal alpha-globin genotype (alpha-alpha/alpha-alpha), and those who were either heterozygous (-alpha/alpha-alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha-thalassemia, because alpha-thalassemia modulates the HbS concentration in HBAS. The urinary concentrating ability was less in the alpha-alpha/alpha-alpha genotype than in the -alpha/alpha-alpha or -alpha/-alpha genotypes (P < 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/-alpha genotype than with the -alpha/alpha-alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (p < 0.05); patients with the -alpha/alpha-alpha genotype had greater concentrating ability than individuals with a normal alpha-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P < 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the alpha-globin genotype. C1 UNIV MISSISSIPPI,MED CTR,SCH MED,DEPT MED,DIV NEPHROL,2500 N STATE ST,JACKSON,MS 39216. UNIV MISSISSIPPI,MED CTR,SCH MED,VET AFFAIRS MED CTR,JACKSON,MS 39216. NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. RP KIRCHNER, KA (reprint author), UNIV MISSISSIPPI,MED CTR,SCH MED,DEPT MED,DIV NEPHROL,2500 N STATE ST,JACKSON,MS 39216, USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 46 TC 46 Z9 46 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1991 VL 88 IS 6 BP 1963 EP 1968 DI 10.1172/JCI115521 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GU967 UT WOS:A1991GU96700023 PM 1752955 ER PT J AU HORIKOSHI, S MCCUNE, BK RAY, PE KOPP, JB SPORN, MB KLOTMAN, PE AF HORIKOSHI, S MCCUNE, BK RAY, PE KOPP, JB SPORN, MB KLOTMAN, PE TI WATER-DEPRIVATION STIMULATES TRANSFORMING GROWTH-FACTOR-BETA-2 ACCUMULATION IN THE JUXTAGLOMERULAR APPARATUS OF MOUSE KIDNEY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA; JUXTAGLOMERULAR APPARATUS HYPERPLASIA; ARTERIAL SMOOTH MUSCLE; RENIN; ANGIOTENSIN-II ID SMOOTH-MUSCLE CELLS; FACTOR TGF-BETA; ANGIOTENSIN-II; EXPRESSION; MICE; HYPERTROPHY AB Transforming growth factor-beta (TGF-beta) modulates the growth and differentiation of many cells and often functions in an autocrine or paracrine fashion. The myoepithelial cells of the renal juxtaglomerular apparatus (JGA) synthesize and secrete renin. Under conditions which chronically stimulate renin production, the JGA undergoes hypertrophy and hyperplasia. The molecular factors responsible for these changes in the JGA have not been identified. In the present study, plasma renin activity was stimulated in the mouse by water deprivation. Using immunoperoxidase staining with specific antibodies against TGF-beta-1, beta-2, and beta-3, we found increased TGF-beta-2 accumulation in the JGA and interlobular arteries. Immunostaining with renin antiserum demonstrated colocalization of TGF-beta-2 and renin. TGF-beta-1 and beta-3 expression was not different between control and water-deprived mice. Our results suggest that in the setting of water deprivation, TGF-beta-2 is localized in a manner which would allow it to act either as a growth factor for or as a phenotypic modulator of the JGA and renal arterioles. C1 NIDR,LAB,30-433,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP KLOTMAN, PE (reprint author), NIDR,LAB,30-433,BETHESDA,MD 20892, USA. NR 28 TC 46 Z9 46 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1991 VL 88 IS 6 BP 2117 EP 2122 DI 10.1172/JCI115541 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GU967 UT WOS:A1991GU96700043 PM 1752966 ER PT J AU PARRILLA, R MIXSON, AJ MCPHERSON, JA MCCLASKEY, JH WEINTRAUB, BD AF PARRILLA, R MIXSON, AJ MCPHERSON, JA MCCLASKEY, JH WEINTRAUB, BD TI CHARACTERIZATION OF 7 NOVEL MUTATIONS OF THE C-ERBA-BETA GENE IN UNRELATED KINDREDS WITH GENERALIZED THYROID-HORMONE RESISTANCE - EVIDENCE FOR 2 HOT-SPOT REGIONS OF THE LIGAND-BINDING DOMAIN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MUTATIONS; C-ERBA; THYROID RESISTANCE GENE ID MESSENGER-RNA; ENZYMATIC AMPLIFICATION; GLUCOCORTICOID RECEPTOR; NEGATIVE REGULATION; DNA-POLYMERASE; GENOMIC DNA; TRANSCRIPTION; PROTEIN; MEDIATE; TRIIODOTHYRONINE AB Genetic analysis in our laboratory of families with generalized thyroid hormone resistance (GTHR) has demonstrated tight linkage with a locus, c-erbA-beta, encoding a nuclear T3 receptor. Three point mutations and two deletions in this locus have previously been reported in affected individuals in unrelated families as potential molecular bases for this disorder. In the present study, we have used direct sequencing of polymerase chain reaction-amplified exons of the c-erbA-beta gene to rapidly identify novel point mutations from seven previously uncharacterized kindreds with GTHR. Six single base substitutions and one single base insertion were identified and found to be clustered in two regions of exons 9 and 10 in the ligand binding domain of the receptor: in the distal ligand-binding subdomain L2 and across the juncture of the tau(i) and dimerization subdomains. Reduction of T3-binding affinity in each of four mutations tested as well as segregation of all mutations to clinically affected individuals strongly supports the hypothesis that these changes are the cause of GTHR in these kindreds. In view of the diversity of clinical phenotypes manifested, the distinct topographic clustering of the mutations provides an invaluable genetic tool for the molecular dissection of thyroid receptor function. C1 NIDDKD,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP WEINTRAUB, BD (reprint author), NIH,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. RI Parrilla, Roberto/B-6307-2008 NR 56 TC 203 Z9 205 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1991 VL 88 IS 6 BP 2123 EP 2130 DI 10.1172/JCI115542 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GU967 UT WOS:A1991GU96700044 PM 1661299 ER PT J AU PAI, LH BOOKMAN, MA OZOLS, RF YOUNG, RC SMITH, JW LONGO, DL GOULD, B FRANKEL, A MCCLAY, EF HOWELL, S REED, E WILLINGHAM, MC FITZGERALD, DJ PASTAN, I AF PAI, LH BOOKMAN, MA OZOLS, RF YOUNG, RC SMITH, JW LONGO, DL GOULD, B FRANKEL, A MCCLAY, EF HOWELL, S REED, E WILLINGHAM, MC FITZGERALD, DJ PASTAN, I TI CLINICAL-EVALUATION OF INTRAPERITONEAL PSEUDOMONAS EXOTOXIN IMMUNOCONJUGATE OVB3-PE IN PATIENTS WITH OVARIAN-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NUDE-MOUSE MODEL; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; PHASE-I; IMMUNOTOXIN; THERAPY; MICE C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,37-4E16,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. FREDERICK CANC RES FACIL,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. DUKE UNIV,MED CTR,DEPT MED,DIV HEMATOL ONCOL,DURHAM,NC 27710. UNIV CALIF SAN DIEGO,CTR CANC,SAN DIEGO,CA 92103. NR 19 TC 94 Z9 94 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1991 VL 9 IS 12 BP 2095 EP 2103 PG 9 WC Oncology SC Oncology GA GT515 UT WOS:A1991GT51500004 PM 1960550 ER PT J AU OSHAUGHNESSY, JA WITTES, RE BURKE, G FRIEDMAN, MA JOHNSON, JR NIEDERHUBER, JE ROTHENBERG, ML WOODCOCK, J CHABNER, BA TEMPLE, R AF OSHAUGHNESSY, JA WITTES, RE BURKE, G FRIEDMAN, MA JOHNSON, JR NIEDERHUBER, JE ROTHENBERG, ML WOODCOCK, J CHABNER, BA TEMPLE, R TI COMMENTARY CONCERNING DEMONSTRATION OF SAFETY AND EFFICACY OF INVESTIGATIONAL ANTICANCER AGENTS IN CLINICAL-TRIALS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP OSHAUGHNESSY, JA (reprint author), NCI,DIV CANC TREATMENT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 0 TC 62 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1991 VL 9 IS 12 BP 2225 EP 2232 PG 8 WC Oncology SC Oncology GA GT515 UT WOS:A1991GT51500021 PM 1960563 ER PT J AU VITIELLO, B HILL, JL ELIA, J CUNNINGHAM, E MCLEER, SV BEHAR, D AF VITIELLO, B HILL, JL ELIA, J CUNNINGHAM, E MCLEER, SV BEHAR, D TI PRN MEDICATIONS IN CHILD PSYCHIATRIC-PATIENTS - A PILOT PLACEBO-CONTROLLED STUDY SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article AB Background: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. Method: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM-III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. Results: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. Conclusion: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity. C1 MED COLL PENN,DEPT PSYCHIAT,DIV CHILD PSYCHIAT,PHILADELPHIA,PA 19129. RP VITIELLO, B (reprint author), NIMH,CLIN SCI LAB,10-3D-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 25 Z9 25 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 1991 VL 52 IS 12 BP 499 EP 501 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA GW882 UT WOS:A1991GW88200005 PM 1752851 ER PT J AU DESIMONE, R AF DESIMONE, R TI FACE-SELECTIVE CELLS IN THE TEMPORAL CORTEX OF MONKEYS SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Review ID INFEROTEMPORAL CORTEX; VISUAL PROPERTIES; NEURONS; SULCUS; RESPONSES; MACAQUE; RECOGNITION; DIRECTION; IDENTITY; LOBE AB The notion of a neuron that responds selectively to the image of a particular complex object has been controversial ever since Gross and his colleagues reported neurons in the temporal cortex of monkeys that were selective for the sight of a monkey's hand (Gross, Rocha-Miranda, & Bender, 1972). Since that time, evidence has mounted for neurons in the temporal lobe that respond selectively to faces. The present paper presents a critical analysis of the evidence for face neurons and discusses the implications of these neurons for models of object recognition. The paper also presents some possible reasons for the evolution of face neurons and suggests some analogies with the development of language in humans. RP DESIMONE, R (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 9,BETHESDA,MD 20892, USA. NR 39 TC 339 Z9 351 U1 2 U2 18 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD WIN PY 1991 VL 3 IS 1 BP 1 EP 8 DI 10.1162/jocn.1991.3.1.1 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA FC735 UT WOS:A1991FC73500002 PM 23964801 ER PT J AU PIVER, WT LINDSTROM, FT AF PIVER, WT LINDSTROM, FT TI NUMERICAL-METHODS FOR DESCRIBING CHEMICAL-TRANSPORT IN THE UNSATURATED ZONE OF THE SUBSURFACE SO JOURNAL OF CONTAMINANT HYDROLOGY LA English DT Article AB Finite-difference and finite-element methods of approximation have been extended to solve the one-dimensional nonlinear partial differential equations that describe the simultaneous transport of heat, moisture and chemical in the unsaturated zone. Especially for chemical transport, nodal spacing criteria are required to minimize numerical dispersion and oscillatory behavior in the solution vector for chemical concentration. Conservative criteria for nodal spacing for saturated flow can be used to set nodal spacing for unsaturated zone transport. When nodal spacing criteria are satisfied, for the same set of transport and boundary conditions, chemical concentration profiles calculated by the two numerical methods will be almost the same. A situation that is simulated very well with one-dimensional models, is the application of chemicals to land surfaces. To compare and contrast the characteristics of solutions given by the two numerical methods, moisture content, temperature and chemical concentration profiles for a 75-day period after application in the unsaturated zone are calculated for two representative types of organic chemicals. In the first, the chemical is very slowly degraded in the subsurface environment but strongly sorbed to soil surfaces. In the second, the chemical is rapidly degraded but weakly sorbed to soil surfaces. Because of differences in sorption coefficients and mechanisms of degradation, for the same set of hydrodynamic properties of the subsurface, the weakly sorbed chemical is more widely distributed throughout the unsaturated zone, whereas the strongly sorbed chemical stays very close to where it is put initially with little penetration into the subsurface. Satisfying nodal spacing criteria minimizes the impact of the method of approximation on the calculated solutions of the transport equations. For better model predictive performance, however, there are needs for more fundamental information on processes governing transport in the subsurface. RP PIVER, WT (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-7722 J9 J CONTAM HYDROL JI J. Contam. Hydrol. PD DEC PY 1991 VL 8 IS 3-4 BP 243 EP 262 DI 10.1016/0169-7722(91)90022-S PG 20 WC Environmental Sciences; Geosciences, Multidisciplinary; Water Resources SC Environmental Sciences & Ecology; Geology; Water Resources GA HB636 UT WOS:A1991HB63600003 ER PT J AU MAJEWSKA, MD VAUPEL, DB AF MAJEWSKA, MD VAUPEL, DB TI STEROID CONTROL OF UTERINE MOTILITY VIA GAMMA-AMINOBUTYRIC ACIDA RECEPTORS IN THE RABBIT - A NOVEL MECHANISM SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GABAA-RECEPTOR; BINDING-SITES; FALLOPIAN-TUBE; CONTRACTILE RESPONSES; PREGNENOLONE-SULFATE; GESTATIONAL CHANGES; RAT OVARY; UTERUS; BRAIN; IDENTIFICATION AB Gamma-aminobutyric acid (GABA) is a regulator of uterine motility. Stimulation of GABA(A) receptors tonically inhibited contractions of rabbit uterine strips, while stimulation of GABA(B) receptors enhanced contractions. Steroids appeared to interact with GABA(A) receptors to modulate uterine contractility: tetra-hydroprogesterone (THP) inhibited while pregnenolone sulphate (PS) increased contractions. THP rapidly antagonized the stimulatory effect of PS, but progesterone inhibited the contractions after a delay, suggesting that the known 'silencing' actions of progesterone on the uterus could be mediated via the metabolite THP, which potentiates the inhibitory function of GABA(A) receptors. This novel mechanisms may play a role in uterine function during pregnancy and parturition. RP MAJEWSKA, MD (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 34 TC 33 Z9 35 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 1991 VL 131 IS 3 BP 427 EP 434 DI 10.1677/joe.0.1310427 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GX007 UT WOS:A1991GX00700012 PM 1664449 ER PT J AU JICHA, DL MULE, JJ ROSENBERG, SA AF JICHA, DL MULE, JJ ROSENBERG, SA TI INTERLEUKIN-7 GENERATES ANTITUMOR CYTOTOXIC LYMPHOCYTES-T AGAINST MURINE SARCOMAS WITH EFFICACY IN CELLULAR ADOPTIVE IMMUNOTHERAPY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GROWTH-FACTOR; STIMULATORY FACTOR; THYMOCYTES; CELLS; IL-7; PROLIFERATION AB Interleukin 7 (IL-7) is a 25-kD cytokine that was initially described as a pre-B cell growth factor. This cytokine has also been shown to have T cell proliferative and differentiation effects. In this report, we demonstrate that antitumor cytotoxic T lymphocytes (CTL) generated by secondary in vitro sensitization of draining lymph node cells in IL-7 are effective in treating 3-day syngeneic methylcholanthrene (MCA) sarcoma pulmonary metastases in mice. In vivo titrations comparing IL-7 to IL-2 antitumor CTL show that they have equivalent potency in adoptive immunotherapy. IL-7 antitumor CTL generated against MCA sarcomas of weak immunogeneity are also tumor specific in their in vivo efficacy. This study represents the first successful use of a cytokine other than IL-2 for the generation of cells with in vivo efficacy in cellular adoptive transfer. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892. NR 18 TC 106 Z9 106 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1991 VL 174 IS 6 BP 1511 EP 1515 DI 10.1084/jem.174.6.1511 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GU644 UT WOS:A1991GU64400024 PM 1744582 ER PT J AU FREY, JL BINO, T KANTOR, RRS SEGAL, DM GIARDINA, SL RODER, J ANDERSON, S ORTALDO, JR AF FREY, JL BINO, T KANTOR, RRS SEGAL, DM GIARDINA, SL RODER, J ANDERSON, S ORTALDO, JR TI MECHANISM OF TARGET-CELL RECOGNITION BY NATURAL-KILLER-CELLS - CHARACTERIZATION OF A NOVEL TRIGGERING MOLECULE RESTRICTED TO CD3- LARGE GRANULAR LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTO-TOXIC CELLS; MONOCLONAL-ANTIBODY; PERIPHERAL-BLOOD; ANTIGEN RECEPTOR; EFFECTOR-CELLS; LGL; RAT; IDENTIFICATION; INTERFERON; ACTIVATION AB In an attempt to identify a molecule in target recognition by CD3- large granular lymphocytes (LGL), we have generated a rabbit antiidiotypic (anti-ID) serum against a monoclonal antibody (mAb 36) that reacted with the cell membrane of K562. Flow cytometry analysis demonstrated that the anti-ID serum bound selectively to CD3- LGL and that F(ab')2 fragments of the anti-ID serum blocked both target cell binding and lysis by NK cells. Stimulation of CD3- LGL with F(ab')2 fragments resulted in the release of serine esterases and the secretion of interferon gamma. Furthermore, anti-ID F(ab')2 antibodies crosslinked to anti-DNP F(ab')2 mediated directed cytotoxicity of a non-natural killer (NK)-susceptible mouse target (YAC-1) via this surface ligand. These functional reactivities were only removed by adsorption with the specific idiotype. Protein analysis showed that the anti-ID serum immunoprecipitated 80-, 110-, and 150-kD proteins. Using this anti-ID, a partial cDNA was cloned and an antipeptide antiserum was made against the portion of the predicted amino acid sequence that corresponded to a portion of the ID binding region. This antipeptide serum exhibited similar functional and biochemical reactivities to those observed with the anti-ID serum. These data suggest that the cell surface moiety recognized by the anti-ID and anti-p104 is novel and is selectively involved in both recognition and triggering of NK-mediated lytic function. C1 NCI, FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB, BIOL RESPONSE MODIFERS PROGRAM,BLDG 560, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL CARCINOGENESIS & DEV PROGRAM, PROGRAM RESOURCES INC, FREDERICK, MD 21702 USA. NIH, IMMUNOL BRANCH, BETHESDA, MD 20892 USA. MT SINAI HOSP, RES INST, TORONTO M5G 1X5, ONTARIO, CANADA. NATL RES COUNCIL BIOTECHNOL RES INST, DIV MOLEC IMMUNOL, MONTREAL A4P 2P2, QUEBEC, CANADA. RI Roder, John/G-6468-2013 FU NCI NIH HHS [N01-CO-74102] NR 41 TC 58 Z9 58 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1991 VL 174 IS 6 BP 1527 EP 1536 DI 10.1084/jem.174.6.1527 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GU644 UT WOS:A1991GU64400026 PM 1720812 ER PT J AU SCHNEIDER, H GRIFFISS, JM BOSLEGO, JW HITCHCOCK, PJ ZAHOS, KM APICELLA, MA AF SCHNEIDER, H GRIFFISS, JM BOSLEGO, JW HITCHCOCK, PJ ZAHOS, KM APICELLA, MA TI EXPRESSION OF PARAGLOBOSIDE-LIKE LIPOOLIGOSACCHARIDES MAY BE A NECESSARY COMPONENT OF GONOCOCCAL PATHOGENESIS IN MEN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NEISSERIA-GONORRHOEAE; POLYACRYLAMIDE GELS; LIPOPOLYSACCHARIDES; HETEROGENEITY; MENINGITIDIS; INFLUENZAE AB To learn how lipooligosaccharide (LOS) phase variations affect pathogenesis, we studied two male volunteers who were challenged intraurethrally with Neisseria gonorrhoeae that make a single LOS of 3,600 daltons and sequentially followed LOS expression by gonococci as urethritis developed. LOS variation occurred in vivo. Signs and symptoms of gonorrhea began with the appearance of variants making 4,700-dalton LOS that are immunochemically similar to glycosphingolipids of human hematopoietic cells (Mandrell, R. E., J. M. Griffiss, and B. A. Macher. 1989. J. Exp. Med. 168:107) and that have acceptors for sialic acid. A variant that appeared at the onset of leukorrhoea was shed by 34/36 men with naturally acquired gonorrhea at the time they sought medical attention; the other two shed the variant associated with dysuria. None shed the challenge variant. These data show that in vivo phase shifts to higher molecular mass LOS that mimic human cell membrane glycolipids are associated with the development of gonococcal leukorrhea. C1 UNIV CALIF SAN FRANCISCO,CTR IMMUNOCHEM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. FIRST ARMY AUGMENTAT DETACHMENT,FT GEORGE G MEADE,MD 20755. NIH,ROCKY MT LABS,HAMILTON,MT 59840. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. SUNY BUFFALO,DEPT MED,BUFFALO,NY 14215. SUNY BUFFALO,DEPT MICROBIOL,BUFFALO,NY 14215. RP SCHNEIDER, H (reprint author), WALTER REED ARMY MED CTR,DEPT BACTERIAL DIS,WASHINGTON,DC 20307, USA. FU NIAID NIH HHS [AI-18384, AI-21620] NR 21 TC 129 Z9 130 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1991 VL 174 IS 6 BP 1601 EP 1605 DI 10.1084/jem.174.6.1601 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GU644 UT WOS:A1991GU64400034 PM 1744587 ER PT J AU COX, JH BENNINK, JR YEWDELL, JW AF COX, JH BENNINK, JR YEWDELL, JW TI RETENTION OF ADENOVIRUS-E19 GLYCOPROTEIN IN THE ENDOPLASMIC-RETICULUM IS ESSENTIAL TO ITS ABILITY TO BLOCK ANTIGEN PRESENTATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-I ANTIGENS; TRANSMEMBRANE PROTEINS; GOLGI-APPARATUS; E3/19K PROTEIN; LYMPHOCYTES-T; SIALOGLYCOPROTEIN; RECOGNITION; EXPRESSION; TRANSPORT; SEQUENCES AB The E3/19K glycoprotein of adenovirus functions to diminish recognition of adenovirus-infected cells by major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) by binding intracellular class I molecules and preventing them from reaching the plasma membrane. In the present study we have characterized the nature of the interaction between E3/19K and the H-2K(d) (K(d)) molecule. An E3/19K molecule genetically engineered to terminate six residues from its normal COOH terminus (DELTA-E19), was found to associate with K(d) in a manner indistinguishable from wild-type E3/19K. Unlike E3/19K, however, DELTA-E19 was transported through the Golgi complex to the plasma membrane, where it could be detected biochemically and immunocytochemically using a monoclonal antibody specific for the lumenal domain of E3/19K. Importantly, DELTA-E19 also differed from E3/19K in being unable to prevent the presentation of K(d)-restricted viral proteins to CTLs. This is unlikely to be due to DELTA-E19 having a lower avidity for K(d) than E3/19K, since DELTA-E19 was able to compete with E3/19K for K(d) binding, both physically, and functionally in nullifying the E3/19K blockade of antigen presentation. These findings indicate that the ability of E3/19K to block antigen presentation is due solely to its ability to retain newly synthesized class I molecules in the endoplasmic reticulum. RP COX, JH (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 27 TC 96 Z9 97 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1991 VL 174 IS 6 BP 1629 EP 1637 DI 10.1084/jem.174.6.1629 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GU644 UT WOS:A1991GU64400037 PM 1836014 ER PT J AU ANTHONY, LSD GU, M COWLEY, SC LEUNG, WWS NANO, FE AF ANTHONY, LSD GU, M COWLEY, SC LEUNG, WWS NANO, FE TI TRANSFORMATION AND ALLELIC REPLACEMENT IN FRANCISELLA SPP SO JOURNAL OF GENERAL MICROBIOLOGY LA English DT Article ID FORMERLY YERSINIA-PHILOMIRAGIA; TULARENSIS; TULAREMIA; INFECTION; RESISTANCE; PLASMIDS; CLONING; IDENTIFICATION; MUTAGENESIS; DISEASE AB We describe methods for transposon mutagensis and allelic replacement in the facultative intracellular pathogen Francisella. Recombinant clones were constructed by insertion of partially cut F. tularensis or F. novicida DNA into pUC19 and then mutagenized with a mini-Tn10-Km transposon. F. novicida could be transformed with these plasmids either by a chemical transformation method or by electroporation, whereas F. tularensis could be transformed only by electroporation. Transformation of F. tularensis by electroporation was enhanced in the absence of the capsule. Southern blot analysis showed that the Km(R) marker was rescued either by integration of the plasmid into the Francisella chromosome or by allelic replacement. Allelic replacement was found to be the mechanism underlying a site-specific mutation affecting FopA, an outer-membrane protein of Francisella. F. novicida could also be transformed with chromosomal DNA carrying the Km(R) marker and the transformation frequency obtained using chromosomal DNA was generally greater than that obtained using plasmid DNA. F. novicida was also transformed by an IncQ plasmid conataining an F. novicida DNA insert, which replicated autonomously in this host. C1 UNIV VICTORIA,DEPT BIOCHEM & MICROBIOL,VICTORIA V8W 3P6,BC,CANADA. NIH,HLTH & HUMAN SERV,MICROBIAL STRUCT & FUNCT LAB,ROCKY MTN LABS,HAMILTON,MT 59840. NR 29 TC 48 Z9 48 U1 1 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1287 J9 J GEN MICROBIOL JI J. Gen. Microbiol. PD DEC PY 1991 VL 137 BP 2697 EP 2703 PN 12 PG 7 WC Microbiology SC Microbiology GA GX946 UT WOS:A1991GX94600003 PM 1791425 ER PT J AU SHEPHERD, GMG ASSAD, JA PARAKKEL, M KACHAR, B COREY, DP AF SHEPHERD, GMG ASSAD, JA PARAKKEL, M KACHAR, B COREY, DP TI MOVEMENT OF THE TIP-LINK ATTACHMENT IS CORRELATED WITH ADAPTATION IN BULLFROG SACCULAR HAIR-CELLS SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. NIDCD,MOLEC OTOL LAB,BETHESDA,MD. RI Shepherd, Gordon/F-2679-2010 NR 6 TC 3 Z9 3 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1991 VL 98 IS 6 BP A25 EP A25 PG 1 WC Physiology SC Physiology GA GW479 UT WOS:A1991GW47900058 ER PT J AU COLLINS, PL MOTTET, G AF COLLINS, PL MOTTET, G TI POSTTRANSLATIONAL PROCESSING AND OLIGOMERIZATION OF THE FUSION GLYCOPROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TRANS-GOLGI CISTERNAE; ENDOPLASMIC-RETICULUM; F-GLYCOPROTEIN; PROTEIN; ACTIVATION; COMPLEX; OLIGOSACCHARIDES; HEMAGGLUTININ; POLYPEPTIDES; KINETICS AB The post-translational maturation of the fusion protein (F) of human respiratory syncytial virus was investigated. Chemical cross-linking experiments indicated that F forms homotetramers and provided evidence that the intermonomer contacts involve primarily the F1 subunit. Homooligomerization as measured by sedimentation in sucrose gradients was insensitive to carbonyl cyanide m-chlorophenylhydrazone, indicating that it occurs in the endoplasmic reticulum. Cleavage of the F0 precursor to yield the F1 and F2 subunits was blocked by monensin or brefeldin A, indicating that it takes place in distal cisternae of the trans Golgi compartment or in the more distal trans Golgi network. The F0 precursor was not detected at the cell surface in surface immunoprecipitation experiments, indicating that cleavage is intracellular. The appearance of the cleaved F1 protein at the cell surface was concurrent with that of the attachment glycoprotein (G); this and other information indicated that the type 2 membrane orientation of G is not obligatorily associated with a reduced transit rate. Examination of F maturation in the presence of tunicamycin provided evidence that its expression at the cell surface depends upon cleavage and not directly upon glycosylation. C1 UNIV GENEVA,DEPT MICROBIOL,CMU,CH-1211 GENEVA 4,SWITZERLAND. RP COLLINS, PL (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892, USA. NR 34 TC 92 Z9 94 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 1991 VL 72 BP 3095 EP 3101 DI 10.1099/0022-1317-72-12-3095 PN 12 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA GY555 UT WOS:A1991GY55500028 PM 1765771 ER PT J AU DEMEDINACELI, L MERLE, M AF DEMEDINACELI, L MERLE, M TI HOW EXACT SHOULD NERVE STUMP COAPTATION BE - A NEW ANSWER GIVEN BY CELL SURGERY SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article RP DEMEDINACELI, L (reprint author), ST ELIZABETH HOSP,NIMH,WASHINGTON,DC 20032, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur. Vol. PD DEC PY 1991 VL 16B IS 5 BP 495 EP 498 DI 10.1016/0266-7681(91)90102-T PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA HC715 UT WOS:A1991HC71500006 PM 1791358 ER PT J AU JUENGST, ET AF JUENGST, ET TI THE SURGICAL SOLUTION - A HISTORY OF INVOLUNTARY STERILIZATION IN THE UNITED-STATES - REILLY,PR SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Book Review RP JUENGST, ET (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA BOX 90660, DURHAM, NC 27708-0660 SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD WIN PY 1991 VL 16 IS 4 BP 830 EP 833 DI 10.1215/03616878-16-4-830 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA HB750 UT WOS:A1991HB75000016 ER PT J AU BALL, WD HAND, AR MOREIRA, JE AF BALL, WD HAND, AR MOREIRA, JE TI A NEONATAL SECRETORY PROTEIN ASSOCIATED WITH SECRETION GRANULE MEMBRANES IN DEVELOPING RAT SALIVARY-GLANDS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE RAT SALIVARY GLANDS; IMMUNOCYTOCHEMISTRY; SECRETED PERINATAL MEMBRANE PROTEIN ID PROLINE-RICH PROTEINS; ISOPROTERENOL-TREATED RATS; PAROTID-GLAND; SUBMANDIBULAR-GLAND; CELLS; PHOSPHATIDYLINOSITOL AB In the perinatal submandibular gland, the secretion granules of Type I cells contain protein C (89 KD) and those of Type Ill cells have B1-immunoreactive proteins (B1-IP, 23.5-27.5 KD). In this report we used immunocytochemistry at the light and election microscopic levels to describe the developmental distribution and localization of protein D (175 KD), which is secreted by both Type I and Type III cells. At its first appearance in Type I cells at 18 days and in Type III cells at 19 days post conception, protein D immunoreactivity (D-IR) is associated with secretion granule membranes; this is more pronounced in Type I than in Type III cells. In early postnatal life the label remains membrane associated, but as Type III cells differentiate into seromucous acinar cells, the lower level of label present in these cells is found in the granule content. Label is found associated with the membrane in secretion granules of Type I cells as long as these cells are identifiable in acini, and subsequent to this similarly labeled cells are seen in intercalated ducts. In the sublingual gland (SLG), D-IR is membrane associated in secretion granules of serous demilune cells, and is present in the secretion granule content in mucous acinar cells. D-IR is also found in the lingual serous (von Ebner's) glands, lacrimal gland, and tracheal glands, primarily in the ducts, where it is localized in the content of secretion granules. C1 HOWARD UNIV,COLL MED,HOWARD UNIV CANC CTR,WASHINGTON,DC 20059. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20822. RP BALL, WD (reprint author), HOWARD UNIV,COLL MED,DEPT ANAT,520 W ST NW,WASHINGTON,DC 20059, USA. FU NIDCR NIH HHS [DE-06635] NR 27 TC 18 Z9 19 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1991 VL 39 IS 12 BP 1693 EP 1706 PG 14 WC Cell Biology SC Cell Biology GA GR414 UT WOS:A1991GR41400011 PM 1940321 ER PT J AU FOLEY, JF DIETRICH, DR SWENBERG, JA MARONPOT, RR AF FOLEY, JF DIETRICH, DR SWENBERG, JA MARONPOT, RR TI DETECTION AND EVALUATION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) IN RAT-TISSUE BY AN IMPROVED IMMUNOHISTOCHEMICAL PROCEDURE SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE FORMALIN FIXATION; PARAFFIN PROCESSING; PROLIFERATING CELL NUCLEAR ANTIGEN; SUPER SENSITIVE BIOTIN-STREPTAVIDIN AB Proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, was detected by an improved immunohistochemical procedure (super sensitive biotin-streptavidin), in formalin fixed, paraffin embedded tissue. Small intestine, liver, kidney, testis, and esophagus from rats were stained for the detection and evaluation of PCNA as a suitable marker for cell proliferation. Different patterns of staining that are believed to correlate with the individual phases of the cell cycle (G1, S, G2, M, G0) were recognized. PCNA offers an alternative to established cell labeling techniques for investigating cell proliferation. RP FOLEY, JF (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 85 Z9 85 U1 1 U2 2 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD DEC PY 1991 VL 14 IS 4 BP 237 EP 241 PG 5 WC Cell Biology SC Cell Biology GA GU900 UT WOS:A1991GU90000004 ER PT J AU CARTER, RH TUVESON, DA PARK, DJ RHEE, SG FEARON, DT AF CARTER, RH TUVESON, DA PARK, DJ RHEE, SG FEARON, DT TI THE CD19 COMPLEX OF LYMPHOCYTES-B - ACTIVATION OF PHOSPHOLIPASE-C BY A PROTEIN TYROSINE KINASE-DEPENDENT PATHWAY THAT CAN BE ENHANCED BY THE MEMBRANE IGM COMPLEX SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; MONOCLONAL-ANTIBODY; MOLECULAR MECHANISMS; IMMUNE-RESPONSE; RECEPTOR TYPE-2; PHORBOL ESTER; IMMUNOGLOBULIN; STIMULATION; CD4; PHOSPHORYLATION AB We have investigated the mechanism by which the membrane protein complex of the B lymphocyte that contains CD19 and CR2 activates phospholipase C (PLC) to induce a rise in [Ca2+]i. The CD19 complex resembled the membrane IgM complex in that three protein tyrosine kinase inhibitors suppressed increases in [Ca2+]i and inositol bisphosphate and inositol triphosphate generation. However, the activation of PLC by the CD19 complex could be distinguished from that by the membrane IgM complex by slower kinetics of generation of inositol phosphates, resistance to inhibition by activators of protein kinase C, and different pattern of tyrosine-phosphorylated cellular substrates. Western blot analysis of lysates from cells stimulated by the CD19 complex demonstrated a single new phosphotyrosine-containing protein of 85 kDa, whereas multiple other phosphotyrosine-containing proteins were present in cells activated by the mIgM complex. In particular, PLC-gamma-1, which is a substrate for the protein tyrosine kinase activated by the mIgM complex, was not tyrosine-phosphorylated in cells stimulated by the CD19 complex. Cross-linking the two complexes together caused a synergistic increase in [Ca2+]i which was neither suppressed by activation of protein kinase C nor associated with increased tyrosine-phosphorylation of PLC, characteristic of the CD19 pathway. Therefore, the B cell has two signal transduction complexes, associated with membrane IgM and CD19, that activate PLC by different mechanisms and that can synergistically interact to enhance this function by the CD19 pathway. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP CARTER, RH (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV MOLEC & CLIN RHEUMATOL,614 HUNTERIAN,725 N WOLFE ST,BALTIMORE,MD 21205, USA. RI Park, Do-Joon/J-2736-2012 FU NIAID NIH HHS [AI-22833, AI-28191]; NIGMS NIH HHS [5T32GM07309] NR 45 TC 113 Z9 114 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 DEC 1 PY 1991 VL 147 IS 11 BP 3663 EP 3671 PG 9 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700001 PM 1719083 ER PT J AU RACIOPPI, L RONCHESE, F SCHWARTZ, RH GERMAIN, RN AF RACIOPPI, L RONCHESE, F SCHWARTZ, RH GERMAIN, RN TI THE MOLECULAR-BASIS OF CLASS-II MHC ALLELIC CONTROL OF T-CELL RESPONSES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PIGEON CYTOCHROME-C; MEDIATED GENE-TRANSFER; ANTIGEN-BINDING SITE; LYMPHOCYTE-T; IMMUNOGENIC PEPTIDES; SURFACE EXPRESSION; FINE SPECIFICITY; PROLIFERATIVE RESPONSE; POLYPEPTIDE-CHAIN AB To identify the molecular basis for the effects of MHC molecule polymorphism on T cell responses, we have combined functional T cell response testing with measurements of peptide binding to the class Il MHC molecules on transfected cells. Our studies identify a small subset of spatially localized polymorphic residues of the E-alpha-E-beta-dimer (strand residue-beta-29, and helix residues beta-72 and beta-75) regulating cytochrome c peptide presentation by two distinct mechanisms. The first effect is on quantitative control of net peptide binding. The replacement of the valine found at position beta-29 in E-beta-k with the glutamic acid found in E-beta-b results in a selective loss of pigeon cytochrome peptide but not moth cytochrome peptide binding to the resultant mutant E-alpha-E-beta-k molecule. Reciprocally, the replacement of glutamic acid at beta-29 in E-beta-b with valine results in a gain of pigeon peptide binding. These changes in binding parallel changes in T cell responses in vitro to these peptide E-alpha-E-beta combinations and mirror the in vivo immune response gene phenotypes of mice expressing E-alpha-E-beta-k and E-alpha-E-beta-b. E-alpha-E-beta-s molecules, which have a beta-29 glutamic acid, are nevertheless able to bind and present pigeon cytochrome peptides, and this is due to changes in helix residues beta-72 and beta-75 that compensate for the negative effect of the beta-29 glutamic acid. The second activity is a critical change in the conformation of the peptide bound to the same extent by distinct MHC molecules, as revealed by changes in T cell responses to moth cytochrome peptides presented by two E-alpha-E-beta molecules differing only at position beta-29. Both of these effects can be ascribed to a single polymorphic residue modeled to be inaccessible to TCR contact (beta-29), providing a striking demonstration of how MHC molecule polymorphism can modify T cell-dependent immune responses without direct physical participation in the receptor recognition event. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,9000 ROCKVILLE PK,BLDG 10,RM 11N311,BETHESDA,MD 20892. NIAID,CELLULAR & MOLEC IMMUNOL,BETHESDA,MD 20892. OI racioppi, luigi/0000-0002-9207-6752 NR 67 TC 50 Z9 51 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1991 VL 147 IS 11 BP 3718 EP 3727 PG 10 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700008 PM 1658150 ER PT J AU LINDSBERG, ML BRUNSWICK, M YAMADA, H LEES, A INMAN, J JUNE, CH MOND, JJ AF LINDSBERG, ML BRUNSWICK, M YAMADA, H LEES, A INMAN, J JUNE, CH MOND, JJ TI BIOCHEMICAL-ANALYSIS OF THE IMMUNE B-CELL DEFECT IN XID MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHORBOL-MYRISTATE ACETATE; PROTEIN TYROSINE PHOSPHORYLATION; CBA-N MICE; LYMPHOCYTES-B; SURFACE-IMMUNOGLOBULIN; ANTI-IMMUNOGLOBULIN; MOUSE LYMPHOCYTES; ACTIVATION; PROLIFERATION; CALCIUM AB Previous studies have shown that B cells from xid immune defective CBA/N mice that are unresponsive do not proliferate after stimulation with unconjugated anti-Ig. The experiments in this manuscript demonstrate that dextran-anti-Ig conjugates, which induce extensive and prolonged sIg cross-linking, are able to stimulate proliferation of xid B cells. The ability of these conjugates to stimulate proliferation of xid B cells is not related to their ability to stimulate higher levels Of PIP2 breakdown. Thus, high concentrations of unconjugated anti-Ig antibody, which are nonmitogenic for xid B cells, stimulate higher levels Of PIP2 breakdown and of calcium transients than lower concentrations of dextran-conjugated anti-Ig, which are mitogenic. Although unconjugated anti-Ig does not provide a fully competent signal to stimulate proliferation of xid B cells, it induces a sufficiently stimulatory signal to enable them to enter DNA synthesis in the presence of the protein kinase C activator, indolactam. This suggests that the extent or duration of activation of protein kinase C by anti-Ig may be limiting in xid B cells. To examine whether another recently described pathway of B cell activation is defective in these mice, we studied the induction of early anti-Ig-mediated tyrosine kinase activity in xid B cells. Both unconjugated and dextran-conjugated anti-Ig antibody stimulated comparable but not identical patterns of tyrosine phosphorylation. These data taken together with other findings that the combination of phorbol ester and calcium ionophore stimulates high levels of proliferation in xid B cells suggests that the immune defect of xid B cells may be distal to surface Ig-mediated activation of tyrosine kinase and Of PIP2 breakdown but proximal to PKC activation. Alternatively, the xid immune defect may not result from abnormalities in the early signal transduction pathways, but rather from more distal and/or as yet undefined pathways leading to B cell activation. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,ROOM A3060,4301 JONES BRIDGE RD,BETHESDA,MD 20814. NIH,IMMUNOL LAB,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20814. FU NIAID NIH HHS [R01-AI24273, R01-AI27465] NR 36 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1991 VL 147 IS 11 BP 3774 EP 3779 PG 6 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700015 PM 1719087 ER PT J AU COX, GW CHATTOPADHYAY, U OPPENHEIM, JJ VARESIO, L AF COX, GW CHATTOPADHYAY, U OPPENHEIM, JJ VARESIO, L TI IL-4 INHIBITS THE COSTIMULATORY ACTIVITY OF IL-2 OR PICOLINIC-ACID BUT NOT OF LIPOPOLYSACCHARIDE ON IFN-GAMMA-TREATED MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; HEMATOPOIETIC PROGENITOR CELLS; B-LYMPHOMA LINE; T-CELL; INTERFERON-GAMMA; RIBOSOMAL-RNA; PERITONEAL-MACROPHAGES; RECEPTOR EXPRESSION; HUMAN MONOCYTES; GROWTH-FACTOR AB We reported previously that IL-2 induces tumoricidal activity in IFN-gamma-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-gamma, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-gamma plus IL-2 or IFN-gamma plus LPS. IL-4 inhibited IFN-gamma plus IL-2- but not IFN-gamma plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-gamma-induced expression of mRNA for the p55 (alpha) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-gamma plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2R-alpha mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-gamma plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression. RP COX, GW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 42 TC 27 Z9 27 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 DEC 1 PY 1991 VL 147 IS 11 BP 3809 EP 3814 PG 6 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700020 PM 1940368 ER PT J AU SETTE, A VITIELLO, A FARNESS, P FURZE, J SIDNEY, J CLAVERIE, JM GREY, HM CHESNUT, R AF SETTE, A VITIELLO, A FARNESS, P FURZE, J SIDNEY, J CLAVERIE, JM GREY, HM CHESNUT, R TI RANDOM ASSOCIATION BETWEEN THE PEPTIDE REPERTOIRE OF A2.1 CLASS-I AND SEVERAL DIFFERENT DR CLASS-II MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; IMMUNODOMINANT VIRAL PEPTIDE; HLA MOLECULES; IMMUNOGENIC PEPTIDES; ANTIGEN PRESENTATION; CELL RECOGNITION; MHC RESTRICTION; H-2KB MOLECULE; PROTEIN; BINDING AB The interaction between synthetic peptides and A2.1 class I MHC molecules has been investigated using an inhibition of Ag presentation assay and unbiased peptide sets derived of either viral or eucaryotic origin. For the various sets, strong binding (defined as significant inhibition at the 30-mu-g/ml level) was detected in 7 to 46% of the peptides tested, with an overall frequency of 26%. A set of self-peptides derived from human beta-2 microglobulin was also included in the study. In this case, strong binding was detected in 3 of 15 peptides (20%), thus formally demonstrating a lack of self-/non-self-discrimination at the level of class I molecules. When the whole A2.1-binding database of 105 peptides thus generated was examined by sequence analysis, a significant correlation was found with a recently proposed A2.1-binding motif, whereas no particular positive or negative association was detected between the capacity to bind A2.1 and three different class Il alleles (DR1, DR5, and DR7). Finally, using this approach, several peptides capable of binding both A2.1 and multiple DR alleles have been identified, suggesting possible candidates for development of peptide vaccines eliciting both class I and class II restricted responses. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP SETTE, A (reprint author), CYTEL,3525 JOHN HOPKINS COURT,SAN DIEGO,CA 92121, USA. FU NCI NIH HHS [CA49394]; NIAID NIH HHS [AI25280, AI18634] NR 48 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1991 VL 147 IS 11 BP 3893 EP 3900 PG 8 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700032 PM 1658152 ER PT J AU MISCHAK, H KOLCH, W GOODNIGHT, J DAVIDSON, WF RAPP, U ROSEJOHN, S MUSHINSKI, JF AF MISCHAK, H KOLCH, W GOODNIGHT, J DAVIDSON, WF RAPP, U ROSEJOHN, S MUSHINSKI, JF TI EXPRESSION OF PROTEIN-KINASE-C GENES IN HEMATOPOIETIC-CELLS IS CELL-TYPE-DIFFERENTIATION AND B-CELL-DIFFERENTIATION STAGE SPECIFIC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHORBOL ESTERS; RNA EXPRESSION; ACTIVATION; PROLIFERATION; FAMILY; LINE; HETEROGENEITY; TRANSLOCATION; MACROPHAGES; SUBSTRATE AB We have studied the expression of mRNA encoding all known protein kinase C (PKC) isozymes (alpha, beta, gamma, delta, epsilon, zeta, and eta) in murine tumor cell lines that exemplify hemopoietic cells arrested at different stages of development as well as in normal hemopoietic cells. We demonstrate that some of the isozymes, PKC-alpha, -beta, and -eta, are differentially expressed in different lineages. PKC-alpha and -beta generally are not detectable in myeloid cell lines, where PKC-delta is the predominant isoform. Both PKC-alpha and -beta are abundant in most T and B lymphocytic lines, but steady state levels of PKC-beta mRNA are lowest in plasma cell tumors, which exemplify the terminally differentiated B lymphocyte. In contrast, the levels of PKC-alpha mRNA remain high in plasma cell tumors, and a novel, 2.5-kb PKC-alpha mRNA gains prominence. PKC-eta mRNA is the major PKC isoform expressed in T lymphocytes, but it also is highly abundant in some myeloid lines. PKC-delta is expressed at high levels in all the lines we studied, whereas PKC-epsilon and -zeta are found in most cells but only at rather low levels. Analysis of myeloid clones derived from bipotential B lineage progenitor cell lines suggests that the B cell phenotype is associated with the expression of PKC-alpha. The close correlation of protein levels with mRNA levels indicates that PKC expression in hemopoietic cells is mainly regulated at the level of mRNA. The lineage- and differentiation stage-specific patterns of PKC-isozyme expression presented here suggest the involvement of specific PKC isozymes in differentiation as well as lineage determination of hemopoietic cells. C1 NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RHEIN WESTFAL TH AACHEN,KLINIKUM AACHEN,DEPT BIOCHEM,W-5100 AACHEN,GERMANY. RI Rose-John, Stefan/A-7998-2010; Mischak, Harald/E-8685-2011 OI Rose-John, Stefan/0000-0002-7519-3279; NR 35 TC 143 Z9 144 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1991 VL 147 IS 11 BP 3981 EP 3987 PG 7 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700045 PM 1940380 ER PT J AU RIECKMANN, P WILSON, GL THEVENIN, C HONG, JX KEHRL, JH AF RIECKMANN, P WILSON, GL THEVENIN, C HONG, JX KEHRL, JH TI ANALYSIS OF CIS-ACTING ELEMENTS PRESENT IN THE CD20/B1 ANTIGEN PROMOTER SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-TYPE SPECIFICITY; HUMAN LYMPHOCYTES-B; DR-ALPHA GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEAVY-CHAIN ENHANCER; SEQUENCE ELEMENTS; IMMUNOGLOBULIN ENHANCER; PROTEIN-BINDING; OCTAMER MOTIF; KAPPA-B AB A genomic clone spanning a large portion of the 5' untranscribed region of the CD20 gene was isolated. Deletion analysis of subcloned fragments identified several regulatory elements. A major positive cis-acting element was localized between base pairs -290/-186. A second positive regulatory element was localized between -454/-280 and negative regulatory elements were present in the region between bp -828/-454. The sequence -280/-186 conferred B cell-specific expression on a heterologous, TATA box containing c-fos promoter. Electrophoretic mobility shift assays with overlapping oligonucleotide probes spanning -280/-186 revealed that a 25-bp probe (-225/-201) bound a nuclear protein present in B cell lines expressing the CD20/ B1 antigen but not in Jurkat (T cell), U937 (promonocytic), U251 (glioma), or HeLa cells. To confirm the functional significance of this sequence, a trimer of this region was subcloned into the c-fos promoter containing CAT plasmid. Expression was observed only in BJA-B and HS-Sultan cells but not in CD20/B1- cell lines. This sequence element is also important in phorbol ester-induced CD20 expression in the pre-B cell line BP-697. These results partially characterize several regulatory elements present in the CD20 promoter that are likely important in the B cell-specific expression of the CD20 gene. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 50 TC 18 Z9 18 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 DEC 1 PY 1991 VL 147 IS 11 BP 3994 EP 3999 PG 6 WC Immunology SC Immunology GA GQ837 UT WOS:A1991GQ83700047 PM 1719097 ER PT J AU ALEXANDER, RB ROSENBERG, SA AF ALEXANDER, RB ROSENBERG, SA TI ADOPTIVELY TRANSFERRED TUMOR-INFILTRATING LYMPHOCYTES CAN CURE ESTABLISHED METASTATIC TUMOR IN MICE AND PERSIST LONG-TERM INVIVO AS FUNCTIONAL MEMORY LYMPHOCYTES-T SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TUMOR INFILTRATING LYMPHOCYTES; INTERLEUKIN-2; METASTASES; ADOPTIVE TRANSFER ID DISSEMINATED LEUKEMIA; PROLIFERATE INVIVO; ANTITUMOR-ACTIVITY; GENE-TRANSFER; CELLS; INTERLEUKIN-2; IMMUNOTHERAPY; MELANOMA AB Tumor infiltrating lymphocytes (TILs) are derived from solid tumors by culturing single cell suspensions of the tumors in low dose interleukin-2 (IL-2) and intermittent tumor stimulation. We have investigated the survival of TILs after intravenous injection into tumor-bearing mice. Using several murine transplantable sarcomas, we examined the in vivo survival of TILs derived from B6.PL Thy 1a/CY mice (Thy-1.1), which were used to treat established experimental metastases in C57BL/6N (Thy-1.2) mice. Donor and host lymphoid cells could be clearly distinguished by fluorescence-activated cell sorting. We found that TILs or TILs + IL-2 could extend the survival of and, in some instances, cure established experimental hepatic and pulmonary metastases. Donor TILs could be recovered from treated animals at all time points tested; in mice cured of pulmonary metastases donor TILs could be detected as late as 119 days after intravenous injection even in the absence of exogenous IL-2. The administration of a relatively low dose of IL-2 in vivo to mice receiving TILs increased the number of donor TILs recovered from the lungs of cured animals 5-10-fold at all time points but did not change the period of time during which donor TILs could be detected in vivo. Additionally, TILs could be recovered from animals cured of established metastases and such cells retained their antitumor activity in vivo. Finally, when mice cured of pulmonary metastases by TILs or TILs + IL-2 were rechallenged with tumor, donor TILs specifically accumulated at the site of tumor rechallenge up to 4 months after adoptive transfer of TILs. The data demonstrate that adoptively transferred TILs survive for prolonged periods in cured mice and that these cells retain functional memory T cell characteristics. The data are relevant to ongoing trials of TIL therapy for patients with cancer. RP ALEXANDER, RB (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B56,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD DEC PY 1991 VL 10 IS 6 BP 389 EP 397 DI 10.1097/00002371-199112000-00001 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA GR467 UT WOS:A1991GR46700001 PM 1768672 ER PT J AU POCKAJ, BA ROSENBERG, SA AF POCKAJ, BA ROSENBERG, SA TI LACK OF ANTIHYPERTENSIVE EFFECT OF INTERLEUKIN-2 ADMINISTRATION IN HUMANS SO JOURNAL OF IMMUNOTHERAPY LA English DT Note DE INTERLEUKIN-2; ANTIHYPERTENSIVE EFFECT; HUMANS ID TUMOR-INFILTRATING LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2; IMMUNOTHERAPY; CANCER; CELLS AB A recent study reported that a single bolus dose of interleukin-2 (IL-2) decreased blood pressure to normal in adult hypertensive rats and prevented the development of spontaneous hypertension in young rats. The Surgery Branch of the National Cancer Institute has had extensive experience with the administration of IL-2. A review was performed focusing on the experience of IL-2 administration to cancer patients with established preexisting hypertension. Seventeen evaluable patients were identified. Sixteen of the patients experienced a return of their hypertension with the completion of therapy. One patient was able to stop his antihypertensive medications and remain normotensive for 3 months' follow-up. One normotensive patient developed hypertension after initiating IL-2 therapy. Our data do not demonstrate significant reduction in blood pressure in previously hypertensive patients undergoing high-dose IL-2 therapy. RP POCKAJ, BA (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD DEC PY 1991 VL 10 IS 6 BP 456 EP 459 DI 10.1097/00002371-199112000-00010 PG 4 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA GR467 UT WOS:A1991GR46700010 PM 1768680 ER PT J AU FOX, CH TENNERRACZ, K RACZ, P FIRPO, A PIZZO, PA FAUCI, AS AF FOX, CH TENNERRACZ, K RACZ, P FIRPO, A PIZZO, PA FAUCI, AS TI LYMPHOID GERMINAL-CENTERS ARE RESERVOIRS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FOLLICULAR DENDRITIC CELLS; IMMUNE-DEFICIENCY-SYNDROME; INSITU HYBRIDIZATION; PERIPHERAL-BLOOD; AIDS; HIV-1; NODES; LYMPHADENOPATHY; INFECTION; EXPRESSION AB When radiolabeled RNA was used for in situ hybridization, human immunodeficiency virus type 1 (HIV-1) RNA was found in high concentrations in germinal centers of lymphoid tissues from patients with HIV-1 infection. Most of the signal from hybridized probe was independent of specific cells, being found in the extracellular space of germinal centers in all lymphoid tissues examined from adult patients with Centers for Disease Control (CDC) class 11 and ill disease or pediatric patients with CDC class P-2A disease. Lymphoid tissues from adult patients with CDC class IV infections or pediatric patients with CDC class P-2D disease (including autopsy material) lacked intact germinal centers, and HIV-1 RNA was then found only in rare, isolated cells, with some tissues having no detectable HIV-1 RNA. Thus, in the early stages of HIV infection, germinal centers serve as important reservoirs of free virus in the interstitial spaces, and this reservoir disappears as the germinal centers involute with advancing disease. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. ALLGEMEINES KRANKENHAUS ST GEORG,DEPT HEMATOL,HAMBURG,GERMANY. BERNHARD NOCHT INST TROP MED,DEPT PATHOL,HAMBURG,GERMANY. WALTER REED ARMY MED CTR,ARMED FORCES INST PATHOL,DIV AIDS,WASHINGTON,DC. BERNARD NOCHT INST TROP MED,KORBER LAB,HAMBURG,GERMANY. NR 26 TC 273 Z9 273 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1991 VL 164 IS 6 BP 1051 EP 1057 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GR660 UT WOS:A1991GR66000002 PM 1955708 ER PT J AU DEGROOT, AS CLERICI, M HOSMALIN, A HUGHES, SH BARND, D HENDRIX, CW HOUGHTEN, R SHEARER, GM BERZOFSKY, JA AF DEGROOT, AS CLERICI, M HOSMALIN, A HUGHES, SH BARND, D HENDRIX, CW HOUGHTEN, R SHEARER, GM BERZOFSKY, JA TI HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE T-HELPER EPITOPES IDENTIFIED IN MICE AND HUMANS - CORRELATION WITH A CYTOTOXIC T-CELL EPITOPE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXIC LYMPHOCYTES-T; CIRCUMSPOROZOITE PROTEIN; PROLIFERATIVE RESPONSE; SEROPOSITIVE INDIVIDUALS; PLASMODIUM-FALCIPARUM; SYNTHETIC PEPTIDES; FINE SPECIFICITY; ANTIGENIC SITES; VACCINIA VIRUS; HIV-1 AB T cell immunity may be critical to development of a vaccine for human immunodeficiency virus (HIV-1). T helper epitopes were identified in three predominantly conserved regions in the HIV-1 reverse transcriptase by using reverse transcriptase-immunized mice of five major histocompatibility complex haplotypes. One peptide (residues 38-52) that stimulated H-2k T cells also contained an epitope recognized by cytotoxic T cells from the same mice and from HIV-infected patients. Such concordance between helper and cytotoxic T lymphocyte epitopes, observed in four cases, may be important in vaccine development. Peptide 36-52 was recognized by interleukin-2-producing peripheral blood T cells from 9 of 17 HIV-seropositive humans studied, of multiple human leukocyte antigen-DR and -DQ types. The broad recognition of this peptide by both helper and cytotoxic T cells substantiates its potential importance in a vaccine. C1 NCI, METAB BRANCH, MOLEC IMMUNOGENET & VACCINE RES SECT, BETHESDA, MD 20892 USA. NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES FACIL, ABL BASIC RES PROGRAM, FREDERICK, MD 21701 USA. DEV CTR, FREDERICK, MD USA. USAF, MED CTR, HIV UNIT, LACKLAND AFB, TX 78236 USA. TORREY PINES INST MOLEC STUDIES, SAN DIEGO, CA USA. RI De Groot, Anne/B-6221-2013; Hendrix, Craig/G-4182-2014 OI De Groot, Anne/0000-0001-5911-1459; Hendrix, Craig/0000-0002-5696-8665 NR 59 TC 32 Z9 33 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1991 VL 164 IS 6 BP 1058 EP 1065 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GR660 UT WOS:A1991GR66000003 PM 1720151 ER PT J AU COTTLERFOX, M FOX, CH AF COTTLERFOX, M FOX, CH TI EXAMINING CELLS FOR INFECTIOUS AGENTS - A NOVEL-APPROACH SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP COTTLERFOX, M (reprint author), NIAID,DEPT TRANSFUS MED,BLDG 10-1C711,BETHESDA,MD 20892, USA. NR 3 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1991 VL 164 IS 6 BP 1239 EP 1240 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GR660 UT WOS:A1991GR66000038 PM 1955729 ER PT J AU GRALNICK, HR WILLIAMS, S MCKEOWN, L CONNAGHAN, G SHAFER, B HANSMANN, K VAIL, M FENTON, J AF GRALNICK, HR WILLIAMS, S MCKEOWN, L CONNAGHAN, G SHAFER, B HANSMANN, K VAIL, M FENTON, J TI ENDOGENOUS PLATELET FIBRINOGEN SURFACE EXPRESSION ON ACTIVATED PLATELETS SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; STIMULATED HUMAN-PLATELETS; MURINE MONOCLONAL-ANTIBODY; WILLEBRAND FACTOR BINDING; HUMAN-BLOOD PLATELETS; VONWILLEBRAND-FACTOR; ALPHA-GRANULES; IMMUNOCYTOCHEMICAL LOCALIZATION; HUMAN MEGAKARYOCYTES; RECOGNITION SITE AB Intracellular Platelet fibrinogen surface expression was studied in arabinogalactan-purified, resting, and thrombin-stimulated platelets. Platelet fibrinogen is derived from endocytosis of plasma fibrinogen by megakaryocytes. Like a variety of other adhesive proteins, it is stored in the platelet alpha-granule. Platelet fibrinogen surface expression was studied by using the antigen-binding fragments of a murine monoclonal antibody to platelet fibrinogen, F26, and an immunopurified polyclonal antifibrinogen antibody. Studies correlating platelet fibrinogen surface expression with the presence of the glycoprotein IIb-IIIa (GPIIb-IIIa) complex showed that in the presence of ethylene glycol tetraacetic acid (EGTA) at 37-degrees-C, neither the GPIIb-IIIa complex nor platelet fibrinogen was expressed on the surface of thrombin-activated platelets. Similar experiments performed in the presence of EGTA and calcium showed proportional expression of the GPIIb-IIIa complex and platelet fibrinogen. The addition of Arg-Gly-Asp-Ser-containing peptides, the pentadecapeptide of the fibrinogen alpha-chain carboxy terminus, or the monoclonal antibody 10E5, when directed against the GPIIb-IIIa complex before thrombin activation, inhibited 65% to 94% of the platelet fibrinogen expression, as determined with the polyclonal and monoclonal antigen-binding fragments. When these same inhibitory agents were added immediately after or 5 minutes after thrombin, the amount of inhibition decreased significantly. Similar studies with a washed platelet system revealed that when the inhibitors of platelet fibrinogen expression were added before thrombin stimulation, the degree of inhibition observed was only 24% to 38%. This suggests that the major portion of platelet fibrinogen expression involves the release of platelet fibrinogen and its subsequent binding to GPIIb-IIIa. This binding may occur within the open canalicular system or on the platelet surface; in either case, wherever the site of released platelet fibrinogen binding occurs, it can be markedly inhibited by the RGD-containing peptides and the gamma-chain fibrinogen peptides. Approximately 10% to 30% of platelet fibrinogen may be expressed prebound to a platelet receptor, or else it is released and binds to a platelet receptor other than the GPIIb-IIIa complex. C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. RP GRALNICK, HR (reprint author), NIH,CTR CLIN,HEMATOL SERV,BLDG 10,ROOM 2C390,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL-13160] NR 51 TC 25 Z9 26 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD DEC PY 1991 VL 118 IS 6 BP 604 EP 613 PG 10 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA GT053 UT WOS:A1991GT05300014 PM 1744509 ER PT J AU KAY, LE TORCHIA, DA AF KAY, LE TORCHIA, DA TI THE EFFECTS OF DIPOLAR CROSS-CORRELATION ON C-13 METHYL-CARBON T1, T2, AND NOE MEASUREMENTS IN MACROMOLECULES SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; MODEL-FREE APPROACH; COUPLED SPIN SYSTEMS; NMR-SPECTROSCOPY; RELAXATION-TIMES; STAPHYLOCOCCAL NUCLEASE; PROTEINS; SPECTRA; ASSIGNMENT; DYNAMICS C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP KAY, LE (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 29 TC 102 Z9 104 U1 3 U2 22 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 1991 VL 95 IS 3 BP 536 EP 547 DI 10.1016/0022-2364(91)90167-R PG 12 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA HB723 UT WOS:A1991HB72300007 ER PT J AU ARCHER, SJ IKURA, M TORCHIA, DA BAX, A AF ARCHER, SJ IKURA, M TORCHIA, DA BAX, A TI AN ALTERNATIVE 3D-NMR TECHNIQUE FOR CORRELATING BACKBONE N-15 WITH SIDE-CHAIN H-BETA-RESONANCES IN LARGER PROTEINS SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID 2D NMR-SPECTRA; COUPLING-CONSTANTS; ENRICHED PROTEINS; SPECTROSCOPY C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP ARCHER, SJ (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 320 Z9 321 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 1991 VL 95 IS 3 BP 636 EP 641 DI 10.1016/0022-2364(91)90182-S PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA HB723 UT WOS:A1991HB72300022 ER PT J AU LAL, RB BRODINE, SK COLIGAN, JE ROBERTS, CR AF LAL, RB BRODINE, SK COLIGAN, JE ROBERTS, CR TI DIFFERENTIAL ANTIBODY RESPONSIVENESS TO P19 GAG RESULTS IN SEROLOGICAL DISCRIMINATION BETWEEN HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HTLV-I/II; GAG ANTIBODY; LINEAR EPITOPES ID CELL LEUKEMIA-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; HTLV-II; INFECTION; ANTIGENS; LYMPHOMA; GENE AB A new algorithm based upon the differential antibody responses to two gag gene products (p19 and p24) of human T lymphotropic virus (HTLV) has been suggested for serologic discrimination of HTLV type I (HTLV-I) and type II (HTLV-II) [Lillihoj et al., 1990]. To evaluate the practical usefulness of this algorithm, serum specimens from HTLV-seropositive individuals whose infection was confirmed by PCR analysis to be HTLV-I (n = 60) or HTLV-II (n = 61) were analyzed by western blot. The intensities of the antibody response to p24gag and p19gag were scored by one individual without prior knowledge of PCR results. According to the algorithm, specimens with p19 greater-than-or-equal-to p24 were classified as HTLV-I, whereas specimens with p19 < p24 were classified as HTLV-II. Of 60 PCR confirmed HTLV-I specimens, 56 had p19 greater-than-or-equal-to p24 (93%) while 4 had p19 < p24. Of 61 PCR confirmed HTLV-II specimens, 56 had p19 < p24 (92%) and 5 had p19 greater-than-or-equal-to p24. The overall accuracy of serologic differentiation when using this algorithm was 92%, as 4 of 60 HTLV-I (7%) and 5 of 61 HTLV-II (8%) could have been wrongly classified. Although the differential antibody response to p19gag and p24gag provides a simple means of serologically distinguishing between HTLV-I and HTLV-II infection in population-based epidemiological studies, in a clinical context more accurate means of confirmation are required. The dominant p19gag responses were mapped to the C-terminus of p19 (p19(102-117)). Competitive inhibition of p19gag response by peptide p19(102-107), however, did not abrogate the binding of serum specimens from HTLV-I-infected individuals. C1 USN HOSP,DIV INFECT DIS,SAN DIEGO,CA 92134. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT DIAGNOST RETROVIROL,WASHINGTON,DC 20307. RP LAL, RB (reprint author), CTR DIS CONTROL,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333, USA. NR 21 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1991 VL 35 IS 4 BP 232 EP 236 DI 10.1002/jmv.1890350404 PG 5 WC Virology SC Virology GA GR591 UT WOS:A1991GR59100003 PM 1687064 ER PT J AU THOMPSON, RD SECUNDA, S DALY, JW OLSSON, RA AF THOMPSON, RD SECUNDA, S DALY, JW OLSSON, RA TI ACTIVITY OF N6-SUBSTITUTED 2-CHLOROADENOSINES AT ADENOSINE-A1 AND ADENOSINE-A2 RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ADENOSINE RECEPTORS; AGONISTS; DERIVATIVES; ANALOGS; A1 AB Radioligand binding studies of N6-substituted adenosines at the A1 and A2 adenosine receptors of rat brain cortex and rat brain striatum, respectively, show that a 2-chloro substituent does not consistently change the affinity or the selectivity of these analogues for the A1 receptor. A 2-chloro substituent lowers the characteristic stereoselectivity of the A1 receptor toward the R diasteromer of N6-(1-phenyl-2-propyl)adenosine. A 2-chloro substituent consistently increases potency of N6-substituted adenosines as agonists at an adenosine A2 receptor stimulatory to adenylate cyclase in PC12 cell membranes. C1 UNIV S FLORIDA,DEPT INTERNAL MED,BOX 19,12901 BRUCE B DOWNS BLVD,TAMPA,FL 33612. UNIV S FLORIDA,DEPT BIOCHEM,TAMPA,FL 33612. UNIV S FLORIDA,DEPT MOLEC BIOL,TAMPA,FL 33612. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20289. FU NHLBI NIH HHS [HL-30391] NR 18 TC 18 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC PY 1991 VL 34 IS 12 BP 3388 EP 3390 DI 10.1021/jm00116a007 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GW252 UT WOS:A1991GW25200007 PM 1766003 ER PT J AU MANFREDI, KP BLUNT, JW CARDELLINA, JH MCMAHON, JB PANNELL, LL CRAGG, GM BOYD, MR AF MANFREDI, KP BLUNT, JW CARDELLINA, JH MCMAHON, JB PANNELL, LL CRAGG, GM BOYD, MR TI NOVEL ALKALOIDS FROM THE TROPICAL PLANT ANCISTROCLADUS-ABBREVIATUS INHIBIT CELL KILLING BY HIV-1 AND HIV-2 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter C1 NCI,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NCI,NAT PROD BRANCH,FREDERICK,MD 21702. OI Blunt, John/0000-0003-4053-4376 NR 8 TC 125 Z9 125 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC PY 1991 VL 34 IS 12 BP 3402 EP 3405 DI 10.1021/jm00116a011 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GW252 UT WOS:A1991GW25200011 PM 1766007 ER PT J AU JUENGST, ET AF JUENGST, ET TI GERM-LINE GENE-THERAPY - BACK TO BASICS SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article RP JUENGST, ET (reprint author), NATL CTR HUMAN GENOME RES,BLDG 38A,ROOM 613,BETHESDA,MD 20892, USA. OI Juengst, Eric/0000-0002-8374-5774 NR 18 TC 20 Z9 20 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD DEC PY 1991 VL 16 IS 6 BP 587 EP 592 PG 6 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA GT257 UT WOS:A1991GT25700001 PM 1787388 ER PT J AU RESHKIN, SJ FORGO, J MURER, H AF RESHKIN, SJ FORGO, J MURER, H TI APICAL AND BASOLATERAL EFFECTS OF PTH IN OK CELLS - TRANSPORT INHIBITION, MESSENGER PRODUCTION, EFFECTS OF PERTUSSIS TOXIN, AND INTERACTION WITH A PTH ANALOG SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE CELL POLARITY; PERTUSSIS TOXIN; PARATHYROID HORMONE (PTH); PTH-ANALOGS; INTERNAL MESSENGERS ID OPOSSUM KIDNEY-CELLS; PARATHYROID-HORMONE INHIBITION; NA+ PHOSPHATE COTRANSPORT; COLLECTING TUBULE CELLS; CYCLIC-AMP PRODUCTION; FUNCTIONAL ASYMMETRY; PROXIMAL TUBULE; PROTEIN; MECHANISMS; ASSAY AB The cellular distribution (apical vs. basolateral) of parathyroid hormone (PTH) signal transduction systems in opossum kidney (OK) cells was evaluated by measuring the action of PTH on apically located transport processes (Na/P(i) cotransport and Na/H exchange) and on the generation of intracellular messengers (cAMP and IP3). PTH application led to immediate inhibition of Na/H-exchange without a difference in dose/response relationships between apical and basolateral cell-surface hormone addition (half-maximal inhibition at almost-equal-to 5 x 10(-12) M). PTH required 2-3 hr for maximal inhibition of Na/P(i) cotransport with a half-maximal inhibition occurring at almost-equal-to 5 x 10(-10) M PTH for basolateral application and almost-equal-to 5 x 10(-12) M for apical application. PTH addition to either side of the monolayer produced a dose-dependent production of both cAMP and IP3. Half-maximal activation of IP3 was at about 7 x 10(-12) M PTH and displayed no differences between apical and basolateral hormone addition, while cAMP was produced with a half maximal concentration of 7 x 10(-9) M for apical PTH application and 10(-9) M for basolateral administration. The PTH analog [nle8.18,tyr34]PTH(3-34), (nlePTH), produced partial inhibition of Na/P(i) cotransport (agonism) with no difference between apical and basolateral application. When applied as a PTH antagonist, nlePTH displayed dose-dependent antagonism of PTH inhibition of Na/P(i) cotransport on the apical surface, failing to have an effect on the basolateral surface. Independent of addition to the apical or basolateral cell surface, nlePTH had only weak stimulatory effect on production of cAMP, whereas high levels of IP3 could be measured after addition of this PTH analog to either cell surface. Also an antagonistic action of nlePTH on PTH-dependent generation of the internal messengers, cAMP and IP3, was observed; at the apical and basolateral cell surface nlePTH reduced PTH-dependent generation of cAMP, while PTH-dependent generation of IP3 was only reduced by nlePTH at the apical surface. Pertussis toxin (PT) preincubation produced an attenuation of both PTH-dependent inhibition of Na/P(i) cotransport and IP3 generation while producing an enhancement of PTH-dependent cAMP generation; these effects displayed no cell surface polarity, suggesting that PTH action through either adenylate cyclase or phospholipase C was transduced through similar sets of G-proteins at each cell surface. It is concluded that apparent receptor activities with high and low affinity for PTH exist on both cell surfaces; those with apparent high affinity seem to be coupled preferentially to phospholipase C and those with apparent low affinity to adenylate cyclase. The differences in apparent affinity of receptor events coupled to adenylate cyclase and the differences in PTH/nlePTH interaction on the two cell surfaces are suggestive of the existence of differences in apparent PTH-receptor activities on the two cell surfaces. C1 UNIV ZURICH,DEPT PHYSIOL,CH-8057 ZURICH,SWITZERLAND. RP RESHKIN, SJ (reprint author), NIH,BLDG 10,ROOM 1A06,BETHESDA,MD 20892, USA. NR 31 TC 34 Z9 34 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC PY 1991 VL 124 IS 3 BP 227 EP 237 DI 10.1007/BF01994356 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA GV374 UT WOS:A1991GV37400004 PM 1664860 ER PT J AU KALILFILHO, R GERSTENBLITH, G HANSFORD, RG CHACKO, VP VANDEGAER, K WEISS, RG AF KALILFILHO, R GERSTENBLITH, G HANSFORD, RG CHACKO, VP VANDEGAER, K WEISS, RG TI REGULATION OF MYOCARDIAL GLYCOGENOLYSIS DURING POSTISCHEMIC REPERFUSION SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE GLYCOGEN; PHOSPHORYLASE; ISCHEMIA; C-13-NMR ID NUCLEAR MAGNETIC-RESONANCE; CARDIAC SARCOPLASMIC-RETICULUM; RAT-HEART; METABOLIC INHIBITION; GLUCOSE-METABOLISM; P-31 NMR; C-13; PHOSPHORYLASE; SPECTROSCOPY; GLYCOLYSIS C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CARDIOL, PETER BELFER LAB, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT RADIOL, DIV NMR RES, BALTIMORE, MD 21205 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. FU NHLBI NIH HHS [HL-17655-16] NR 38 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 1991 VL 23 IS 12 BP 1467 EP 1479 DI 10.1016/0022-2828(91)90192-O PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA HJ448 UT WOS:A1991HJ44800012 PM 1811061 ER PT J AU JAWORSKI, CJ CHEPELINSKY, AB PIATIGORSKY, J AF JAWORSKI, CJ CHEPELINSKY, AB PIATIGORSKY, J TI THE ALPHA-A-CRYSTALLIN GENE - CONSERVED FEATURES OF THE 5'-FLANKING REGIONS IN HUMAN, MOUSE, AND CHICKEN SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE PROMOTER; REPETITIVE ELEMENTS; 5'-FLANKING SEQUENCE; CRYSTALLIN GENES; LENS ID HUMAN NUCLEAR-PROTEIN; PROMOTER ELEMENTS; LENS EPITHELIA; REGULATORY ELEMENTS; TRANSGENIC MICE; SEQUENCE MOTIF; ACID SEQUENCES; FAMILY; ALU; DNA AB Approximately 2 kb of 5'-flanking sequences of the lens-specific alpha-A-crystallin genes from human and mouse are presented and compared with similar regions of the chicken gene. A repetitive element was found approximately 1 kb upstream from the coding sequences of the alpha-A-crystallin gene in all three species (Alu in human, B2 in mouse, and CR1 in chicken), suggesting that they may have an important functional or structural role. Despite the ability of alpha-A-crystallin promoters to function across species, dot matrix analyses show only limited similarity among the 600 bp 5' to the structural genes of these three species. The human 5'-flanking sequence is more similar to that of the mouse and chicken than the mouse and chicken are to each other. Numerous short sequences (8-13 bp) are common to all three genes but are distributed differently in each species. The locations and conservation of these sequence motifs suggest functional roles, possibly as cis-regulatory elements of transcription. One motif is similar to the alpha-A-CRYBP1 binding site implicated earlier in the transcriptional regulation of the mouse alpha-A-crystallin gene, and other motifs correspond to sites previously mapped by methylation interference studies in the mouse alpha-A-crystallin promoter. The modular arrangement of conserved sequence motifs is consistent with evolutionary changes occurring at the level of gene regulation. RP JAWORSKI, CJ (reprint author), NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1991 VL 33 IS 6 BP 495 EP 505 DI 10.1007/BF02102802 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA GT508 UT WOS:A1991GT50800004 PM 1779432 ER PT J AU CARTER, CA WOURMS, JP AF CARTER, CA WOURMS, JP TI CELL BEHAVIOR DURING EARLY DEVELOPMENT IN THE SOUTH-AMERICAN ANNUAL FISHES OF THE GENUS CYNOLEBIAS SO JOURNAL OF MORPHOLOGY LA English DT Article ID SALMO-GAIRDNERI RICHARDSON; FUNDULUS DEEP CELLS; NOTHOBRANCHIUS-GUENTHERI; EMBRYONIC DIAPAUSE; SURFACE-ACTIVITY; FATE MAP; LOCOMOTION; MOVEMENTS; GASTRULATION; CONTACT AB Living embryos of three species of South American annual fishes, Cynolebias constanciae, C. nigripinnis, and C. whitei, were observed from fertilization through the 10-somite stage. A description of normal stages of development applicable to all three species of Cynolebias is presented. Cleavage (stages 1-10) is meroblastic and produces a typical teleost blastoderm. Following cleavage (stages 11-13) blastomeres segregate into two populations, viz., 1) a population of deep blastomeres that will disperse as single motile cells, and 2) a hemispherical shell of outer blastomeres that flattens to form an enveloping cell layer (EVL). When epiboly of the EVL and the yolk syncytial layer (YSL) commences (stage 14), deep blastomeres clump together as a consolidation mass and then migrate outward as single cells on the YSL. When epiboly is concluded (stage 19), deep blastomeres have completely dispersed. If diapause does not intervene, the dispersed phase lasts only a few days. Subsequently, the dispersed cells come together to form a definitive aggregate (stage 27). Embryogenesis within the reaggregated mass of previously dispersed cells produces a typical teleost embryo. Early development in Cynolebias resembles that of other South American annual fishes, such as Austrofundulus, in that a phase of deep blastomere dispersion and reaggregation spatially and temporally separates epiboly from embryogenesis. Several features of development markedly differ from Austrofundulus. There are far fewer (250 vs. 2,500) deep blastomeres. Deep cells of Cynolebias are flattened rhomboids with filipodial extensions in contrast to the amoeboid cells of Austrofundulus. Blastomeres of dispersion and reaggregation stages in Cynolebias send out numerous cell surface extensions onto the YSL and in contact with one another, and often line up in rows as do some African annual fishes, e.g., Nothobranchius. During Dispersion II (stage 21), Reaggregation I (stage 22), and Reaggregation II (stage 23), deep cells move in an oriented pattern with respective mean velocities of 3.48 +/- 0.91, 1.28 +/- 0.46, and 1.31 +/- 0.31-mu-m/minute. Cells move toward a granular mass of unknown composition, located at the YSL-yolk interface in the lower hemisphere of the egg. This mass appears to coincide with the site of cell reaggregation. C1 CLEMSON UNIV,DEPT BIOL SCI,CLEMSON,SC 29634. NIEHS,ECMB,RES TRIANGLE PK,NC 27709. NR 55 TC 15 Z9 15 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 0362-2525 J9 J MORPHOL JI J. Morphol. PD DEC PY 1991 VL 210 IS 3 BP 247 EP 266 DI 10.1002/jmor.1052100305 PG 20 WC Anatomy & Morphology SC Anatomy & Morphology GA GT909 UT WOS:A1991GT90900004 PM 1791627 ER PT J AU CHALOVICH, JM YU, LC BRENNER, B AF CHALOVICH, JM YU, LC BRENNER, B TI INVOLVEMENT OF WEAK BINDING CROSSBRIDGES IN FORCE PRODUCTION IN MUSCLE SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Editorial Material ID ACTOMYOSIN ATPASE ACTIVITY; RABBIT PSOAS FIBERS; MYOSIN SUBFRAGMENT-1; TROPONIN-TROPOMYOSIN; HEAVY-MEROMYOSIN; F-ACTIN; CONTAINING FILAMENTS; THIN-FILAMENTS; CALDESMON; SMOOTH C1 NIAMS,PHYS BIOL LAB,BETHESDA,MD. UNIV ULM,DEPT GEN PHYSIOL,W-7900 ULM,GERMANY. RP CHALOVICH, JM (reprint author), E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858, USA. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR40540-01A1, AR35216] NR 35 TC 25 Z9 25 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD DEC PY 1991 VL 12 IS 6 BP 503 EP 506 DI 10.1007/BF01738438 PG 4 WC Cell Biology SC Cell Biology GA GX949 UT WOS:A1991GX94900001 PM 1791190 ER PT J AU BEVER, CT ASOFSKY, R AF BEVER, CT ASOFSKY, R TI AUGMENTED IGG ANTIACETYLCHOLINE RECEPTOR RESPONSE FOLLOWING CHRONIC PENICILLAMINE ADMINISTRATION SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE MYASTHENIA GRAVIS; ANTIACETYLCHOLINE RECEPTOR ANTIBODY; D-PENICILLAMINE ID INDUCED MYASTHENIA-GRAVIS; CELL FUNCTION-INVITRO; RHEUMATOID-ARTHRITIS; IMMUNE-COMPLEXES; INHIBITION; IMMUNOGLOBULINS; PROLIFERATION; ANTIBODIES; MOUSE; CUSO4 AB A model Of D-penicillamine (DP) induced myasthenia gravis (MG) was developed in which the anti-acetylcholine receptor (anti-AChR) antibody response to AChR challenge was increased in mice chronically treated with DP. To investigate the mechanism of the DP induced increase, IgM and IgG anti-AChR responses to AChR challenge were studied. IgG responses were significantly greater in the DP treated mice than in the control group while IgM responses were not significantly different. This change appeared to be relatively specific for the AChR response because neither serum immunoglobulin levels nor the IgG response to a second antigen (purified protein derivative) were increased by DP treatment. These results suggest that a specific sensitization to AChR occurs during chronic DP treatment. C1 UNIV TENNESSEE CTR HLTH SCI,DVAMC,RES SERV,MEMPHIS,TN 38163. UNIV TENNESSEE CTR HLTH SCI,DEPT NEUROL,MEMPHIS,TN 38163. UNIV MARYLAND,DVAMC,RES SERV,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. NIAID,MICROBIAL IMMUN LAB,BETHESDA,MD 20892. RP BEVER, CT (reprint author), UNIV MARYLAND HOSP,DEPT NEUROL,N4W46,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 41 TC 1 Z9 2 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 DEC PY 1991 VL 35 IS 1-3 BP 131 EP 137 DI 10.1016/0165-5728(91)90168-7 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA GR589 UT WOS:A1991GR58900013 PM 1955562 ER PT J AU CARR, DJJ DECOSTA, BR RADESCA, L BLALOCK, JE AF CARR, DJJ DECOSTA, BR RADESCA, L BLALOCK, JE TI FUNCTIONAL ASSESSMENT AND PARTIAL CHARACTERIZATION OF [H-3] (+)-PENTAZOCINE BINDING-SITES ON CELLS OF THE IMMUNE-SYSTEM SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE (+)-PENTAZOCINE; NEUROIMMUNOMODULATION; SIGMA RECEPTOR; MITOGEN-INDUCED PROLIFERATION; INTERLEUKIN-4 ID GUINEA-PIG BRAIN; SIGMA-RECEPTORS; OPIOID RECEPTORS; IDENTIFICATION; PHENCYCLIDINE; LYMPHOCYTES; LEUKOCYTES; ENDOCRINE; AFFINITY; LIGANDS AB The existence of sigma receptors on lymphocytes and thymocytes was characterized using [H-3](+)-pentazocine. [H-3](+)-Pentazocine specifically labels high affinity sigma-type binding sites on T- and B-enriched lymphocyte membranes. The binding is saturable with T lymphocyte sites having a K(D) value of 401 +/- 85 nM and B lymphocyte sites having a K(D) value of 302 +/- 46 nM. Likewise, saturable high (K(D1) 277 +/- 92 nM) and low (K(D2) 2.5 +/- 1.2-mu-M) affinity sites for [H-3](+)-pentazocine are found on thymocytes as well. In competition studies with lymphocytes, the rank order of potency for competing ligands is (+)-pentazocine = N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(l-pyrrolidinyl)ethylamine (BD1008) > IR,2S-(+)-cis-N-(2-(3,4-dichlorophenyl)ethyl]-2-(l-pyrrolidinyl)cyclohexylamine (LR132) greater-than-or-equal-to (-)-pentazocine greater-than-or-equal-to phenazocine > (+/-)-trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulphonate (U-50,488H) = phencyclidine greater-than-or-equal-to haloperidol = 1,3-di-(o)-tolylguanidine. In competition studies with thymocytes, the rank order of potency for competing ligands is (+)-pentazocine = BD1008 greater-than-or-equal-to phenazocine > haloperidol > 1,3-di-(o)-tolylguanidine > phencyclidine > (-)-pentazocine. These compounds were also investigated as potential regulatory molecules in mitogen-stimulated lymphocyte proliferation assays. Of the compounds tested, phencyclidine, 1,3-di-(o)-tolylguanidine, haloperidol, and (+)-pentazocine suppress concanavalin A-induced proliferation at high (10(-5) M) concentrations while (-)-pentazocine is inactive. When pokeweed mitogen or lipopolysaccharide are used, these compounds enhance or suppress lymphocyte proliferation depending on the mitogen and concentration of ligand. These results indicate a stereoselective receptor for (+)-pentazocine which is coupled to biological processes of lymphocytes. C1 UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,UAB STN,BIRMINGHAM,AL 35294. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 34 TC 38 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1991 VL 35 IS 1-3 BP 153 EP 166 DI 10.1016/0165-5728(91)90170-C PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA GR589 UT WOS:A1991GR58900015 PM 1955564 ER PT J AU CARSON, RE AF CARSON, RE TI THE DEVELOPMENT AND APPLICATION OF MATHEMATICAL-MODELS IN NUCLEAR-MEDICINE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP CARSON, RE (reprint author), NIH,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 4 TC 13 Z9 13 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 DEC PY 1991 VL 32 IS 12 BP 2206 EP 2208 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GU534 UT WOS:A1991GU53400044 PM 1744704 ER PT J AU KARP, JS DAUBEWITHERSPOON, ME HOFFMAN, EJ LEWELLEN, TK LINKS, JM WONG, WH HICHWA, RD CASEY, ME COLSHER, JG HITCHENS, RE MUEHLLEHNER, G STOUB, EW AF KARP, JS DAUBEWITHERSPOON, ME HOFFMAN, EJ LEWELLEN, TK LINKS, JM WONG, WH HICHWA, RD CASEY, ME COLSHER, JG HITCHENS, RE MUEHLLEHNER, G STOUB, EW TI PERFORMANCE STANDARDS IN POSITRON EMISSION TOMOGRAPHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article AB A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction. C1 NIH,DEPT PET,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DIV NUCL MED & BIOPHYS,LOS ANGELES,CA 90024. UNIV WASHINGTON,DEPT RADIOL,SEATTLE,WA 98195. JOHNS HOPKINS MED INST,DIV NUCL MED,BALTIMORE,MD 21205. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX 77025. UNIV IOWA,DEPT NUCL MED,IOWA CITY,IA 52242. CTI,PET SYST,KNOXVILLE,TN. POSITRON CORP,HOUSTON,TX. UGM MED SYST,PHILADELPHIA,PA. NUCL SCI CONSULTING SERV,HILLSBORO,MO. GE,MED SYST,MILWAUKEE,WI 53201. RP KARP, JS (reprint author), UNIV PENN,DEPT RADIOL,DONNER 110 HUP,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 3 TC 86 Z9 88 U1 1 U2 2 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 DEC PY 1991 VL 32 IS 12 BP 2342 EP 2350 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GU534 UT WOS:A1991GU53400037 PM 1744726 ER PT J AU HAYUNGA, EG AF HAYUNGA, EG TI MORPHOLOGICAL ADAPTATIONS OF INTESTINAL HELMINTHS SO JOURNAL OF PARASITOLOGY LA English DT Article ID 3 CARYOPHYLLID TAPEWORMS; SITE SELECTION; CESTOIDEA; SCOLEX; PARASITES; PATHOLOGY; WORMS AB Nematodes, trematodes, cestodes, and acanthocephalans each have become adapted in different ways to the microenvironment of the vertebrate intestine. Life in this specialized habitat affords parasites a reliable source of nutrients, a relatively homeostatic environment, and protection from predators but, in exchange for these advantages, presents the special challenges of exposure to digestive enzymes, normal peristalsis, and host immune response to infection. Logically, the surface of the parasite should be the first part of the organism to encounter such challenges, and, for this reason, any response or reaction by the parasite is expected to be manifested at the parasite-host interface. Morphological adaptations of intestinal helminths to their microenvironment include modification of the tegumental surface that affords protection and increases absorptive surface area, development of specialized attachment organs, and, in some cases, complete loss of their own internal digestive system. Representative examples of such adaptations by helminths are described and discussed in terms of the parasite's nutritional requirements, site selection, and host specificity, and the possibility is suggested that some helminths may have adapted in ways that exploit host defensive mechanisms for their own benefit. RP HAYUNGA, EG (reprint author), NIH,DIV RES GRANTS,BETHESDA,MD 20892, USA. NR 50 TC 19 Z9 20 U1 3 U2 10 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD DEC PY 1991 VL 77 IS 6 BP 865 EP 873 DI 10.2307/3282734 PG 9 WC Parasitology SC Parasitology GA HC891 UT WOS:A1991HC89100007 PM 1779289 ER PT J AU PIZZO, PA RUBIN, M FREIFELD, A WALSH, TJ AF PIZZO, PA RUBIN, M FREIFELD, A WALSH, TJ TI THE CHILD WITH CANCER AND INFECTION .2. NONBACTERIAL INFECTIONS SO JOURNAL OF PEDIATRICS LA English DT Review ID INVASIVE PULMONARY ASPERGILLOSIS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LIPOSOMAL-AMPHOTERICIN-B; PNEUMOCYSTIS-CARINII PNEUMONIA; MARROW TRANSPLANT RECIPIENTS; CYTOMEGALO-VIRUS PNEUMONIA; CENTRAL VENOUS CATHETERS; CENTRAL NERVOUS-SYSTEM; OPEN LUNG-BIOPSY; ACUTE-LEUKEMIA RP PIZZO, PA (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NR 105 TC 53 Z9 54 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 DEC PY 1991 VL 119 IS 6 BP 845 EP 857 DI 10.1016/S0022-3476(05)83032-X PG 13 WC Pediatrics SC Pediatrics GA GV185 UT WOS:A1991GV18500001 PM 1660069 ER PT J AU MUELLER, BU BUTLER, KM HUSSON, RN PIZZO, PA AF MUELLER, BU BUTLER, KM HUSSON, RN PIZZO, PA TI PNEUMOCYTSIS-CARINII PNEUMONIA DESPITE PROPHYLAXIS IN CHILDREN WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF PEDIATRICS LA English DT Article ID CHEMOPROPHYLAXIS; TYPE-1; AIDS C1 NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. RP PIZZO, PA (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NR 15 TC 25 Z9 25 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 DEC PY 1991 VL 119 IS 6 BP 992 EP 994 DI 10.1016/S0022-3476(05)83065-3 PG 3 WC Pediatrics SC Pediatrics GA GV185 UT WOS:A1991GV18500032 PM 1960625 ER PT J AU COSTA, PT AF COSTA, PT TI CLINICAL USE OF THE 5-FACTOR MODEL - AN INTRODUCTION SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID PERSONALITY-ASSESSMENT; TEST USAGE RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712 NR 25 TC 45 Z9 45 U1 1 U2 12 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 1991 VL 57 IS 3 BP 393 EP 398 DI 10.1207/s15327752jpa5703_1 PG 6 WC Psychology, Clinical; Psychology, Social SC Psychology GA GP702 UT WOS:A1991GP70200001 PM 1757867 ER PT J AU MCCRAE, RR AF MCCRAE, RR TI THE 5-FACTOR MODEL AND ITS ASSESSMENT IN CLINICAL SETTINGS SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID NEO PERSONALITY-INVENTORY; CALIFORNIA Q-SET; EVALUATING COMPREHENSIVENESS; CONSTRUCT-VALIDITY; NATURAL-LANGUAGE; SELF-REPORTS; SCALES; VALIDATION; RATINGS; MMPI RP MCCRAE, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 62 TC 110 Z9 110 U1 1 U2 12 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 1991 VL 57 IS 3 BP 399 EP 414 DI 10.1207/s15327752jpa5703_2 PG 16 WC Psychology, Clinical; Psychology, Social SC Psychology GA GP702 UT WOS:A1991GP70200002 PM 1757868 ER PT J AU FAGAN, PJ WISE, TN SCHMIDT, CW PONTICAS, Y MARSHALL, RD COSTA, PT AF FAGAN, PJ WISE, TN SCHMIDT, CW PONTICAS, Y MARSHALL, RD COSTA, PT TI A COMPARISON OF 5-FACTOR PERSONALITY DIMENSIONS IN MALES WITH SEXUAL DYSFUNCTION AND MALES WITH PARAPHILIA SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT MEETING OF THE WORLD PSYCHIATRIC ASSOC CY OCT, 1989 CL ATHENS, GREECE SP WORLD PSYCHIAT ASSOC C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP FAGAN, PJ (reprint author), JOHNS HOPKINS MED INST,DEPT PSYCHIAT,SEXUAL BEHAVIOR CONSULTAT UNIT,550 N BROADWAY,SUITE 114,BALTIMORE,MD 21205, USA. NR 38 TC 34 Z9 34 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 1991 VL 57 IS 3 BP 434 EP 448 DI 10.1207/s15327752jpa5703_4 PG 15 WC Psychology, Clinical; Psychology, Social SC Psychology GA GP702 UT WOS:A1991GP70200004 PM 1757870 ER PT J AU LAMB, RJ PRESTON, KL SCHINDLER, CW MEISCH, RA DAVIS, F KATZ, JL HENNINGFIELD, JE GOLDBERG, SR AF LAMB, RJ PRESTON, KL SCHINDLER, CW MEISCH, RA DAVIS, F KATZ, JL HENNINGFIELD, JE GOLDBERG, SR TI THE REINFORCING AND SUBJECTIVE EFFECTS OF MORPHINE IN POSTADDICTS - A DOSE-RESPONSE STUDY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROGRESSIVE-RATIO PERFORMANCE; RHESUS-MONKEYS; METHADONE-MAINTENANCE; 2ND-ORDER SCHEDULES; COCAINE; INJECTION; BEHAVIOR; METHYLPHENIDATE; CHOICE AB The reinforcing and subjective effects of morphine were determined in five human volunteers with histories of i.v. heroin abuse. Subjects responded under a second-order schedule of i.m. injection. Under this schedule, every 100 lever presses produced a brief stimulus light [fixed ratio (FR) 100:s]; the 30th completion of the FR 100 requirement turned on the light for 15 min and the subject received an i.m. injection of morphine [FR 30 (FR 100:s)]. Once each weekday morphine or placebo was available under this schedule. Each drug dose was available for 1 week. Under these conditions placebo did not maintain responding; 3.75 mg of morphine maintained responding in four of five subjects, and higher morphine doses (7.5, 15 and 30 mg) maintained responding in all five subjects. Subjective effects were measured concurrently: these included measures of drug liking, the Morphine Benzedrine Group scale of the Addiction Research Center Inventory, drug detection and identification. Subjects did not report subjective effects different from placebo for the lowest dose of morphine; the intermediate doses of morphine produced inconsistent effects, and the highest dose of morphine occasioned reports of drug liking and "dope" identifications. These results indicate that there can be a significant dissociation of the reinforcing and the subjective effects of opiods, which has implications for theories of opioid abuse, particularly those assuming that the reinforcing effects are casually related to the euphoric effects of opioids. Furthermore, these results confirm that measures of reinforcing effects and measures of subjective effects do not necessarily lead to identical predictions when used to assess the liability for abuse of a substance. C1 NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224. NIDR,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,BEHAV PHARMACOL RES UNIT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. HAHNEMANN UNIV,DEPT MENTAL HLTH SCI,DIV ADDICT RES & TREATMENT,PHILADELPHIA,PA 19102. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Katz, Jonathan/0000-0002-1068-1159 NR 40 TC 153 Z9 154 U1 5 U2 13 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 DEC PY 1991 VL 259 IS 3 BP 1165 EP 1173 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW107 UT WOS:A1991GW10700032 PM 1762068 ER PT J AU REITH, MEA JACOBSON, AE RICE, KC BENUCK, M ZIMANYI, I AF REITH, MEA JACOBSON, AE RICE, KC BENUCK, M ZIMANYI, I TI EFFECT OF METAPHIT ON DOPAMINERGIC NEUROTRANSMISSION IN RAT STRIATAL SLICES - INVOLVEMENT OF THE DOPAMINE TRANSPORTER AND VOLTAGE-DEPENDENT SODIUM-CHANNEL SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PHENCYCLIDINE RECEPTOR ACYLATOR; VESICULAR TRANSMITTER STORES; LOCAL-ANESTHETICS; ACETYLCHOLINE NEUROTRANSMISSION; 20-ALPHA-BENZOATE BINDING; SYNTHESIS INHIBITORS; ENDOGENOUS DOPAMINE; ANTAGONIST ACTIVITY; PCP ANTAGONIST; D-AMPHETAMINE AB Metaphit, an isothiocyanate analog of phencyclidine (PCP), increased the basal release of radioactivity (outflow) from perfused rat striatal slices preloaded with [H-3]dopamine above levels observed with the dopamine uptake blocker nomifensin. Preperfusing the slices with metaphit, followed by its removal, attenuated the amphetamine- or dopamine-induced outflow. In slices prepared from reserpine-pretreated rats, the metaphit (100-mu-M)-induced outflow was reduced to that observed with 10-mu-M nomifensin, suggesting a vesicular releasing effect of metaphit in addition to dopamine uptake blockade. Electrically induced overflow of radioactivity from normal slices was stimulated by nomifensin and PCP, and by metaphit at 3-mu-M; it was unaffected by metaphit at 10 and 25-mu-M, and inhibited by higher concentrations of metaphit. Evidence that the latter effect is due to blockade of voltage-dependent sodium channels is as follows. First, metaphit, as did PCP, inhibited the binding of [H-3]batrachotoxinin A 20-alpha benzoate to rat striatal synaptoneurosomes by increasing its dissociation rate; the effect of PCP, but not that of metaphit, was reversible by washing. Second, metaphit, as did PCP, inhibited veratridine (5-mu-M)-induced influx of [C-14]guanidinium ion into synaptoneurosomes. Third, metaphit inhibited overflow of radioactivity from [H-3]dopamine-preloaded slices induced by 2.5-mu-M veratridine, as did the sodium channel blocker tetrodotoxin. C1 NATHAN S KLINE INST PSYCHIAT RES,CTR NEUROCHEM,WARDS ISL,NY. NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV CALIF DAVIS,DEPT VET PHARMACOL & TOXICOL,DAVIS,CA 95616. RI Reith, Maarten/A-4601-2008 FU NIDA NIH HHS [DA 03025] NR 45 TC 12 Z9 12 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 DEC PY 1991 VL 259 IS 3 BP 1188 EP 1196 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW107 UT WOS:A1991GW10700035 PM 1662274 ER PT J AU BHAT, M AF BHAT, M TI PERIODONTAL HEALTH OF 14-17-YEAR-OLD UNITED-STATES SCHOOLCHILDREN SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE GINGIVITIS; CALCULUS; PERIODONTAL ATTACHMENT LOSS; CHILDRENS SURVEY; DENTAL EPIDEMIOLOGY ID ADOLESCENTS; GINGIVITIS; DISEASE AB This paper describes the findings related to periodontal health in 14-17-year-old children who participated in the National Survey of Oral Health in US Schoolchildren, conducted by the National Institute of Dental Research (NIDR) during 1986-87. Gingivitis was observed in approximately 60 percent of children in this age group. The proportion of examined sites per child with gingivitis, however, was less than 6 percent. Gingivitis was most common in molar areas in the maxilla and incisor areas in the mandible. Supragingival calculus was observed in nearly 34 percent of the children, and subgingival calculus in approximately 23 percent. The proportion of teeth per child with calculus was approximately 8 percent for supragingival and 4 percent for subgingival calculus. Both types of calculus showed a predilection for molars in the maxilla and incisors and cuspids in the mandible. The mean periodontal attachment loss was 0.33 mm. The teeth most frequently affected by attachment loss of 2 mm or more were maxillary molars and bicuspids, followed by mandibular molars and cuspids. RP BHAT, M (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892, USA. NR 23 TC 29 Z9 31 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1991 VL 51 IS 1 BP 5 EP 11 DI 10.1111/j.1752-7325.1991.tb02168.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA FA385 UT WOS:A1991FA38500002 PM 2027103 ER PT J AU FERRIOLA, PC NETTESHEIM, P AF FERRIOLA, PC NETTESHEIM, P TI ALTERATIONS IN GROWTH-FACTOR PATHWAYS IN MULTISTAGE CARCINOGENESIS OF TRACHEAL EPITHELIAL-CELLS SO JOURNAL OF RADIATION RESEARCH LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON RADIATION CARCINOGENESIS IN THE WHOLE-BODY SYSTEM CY DEC 05-06, 1990 CL TOKYO, JAPAN SP JAPAN RADIAT RES SOC, FDN PROMOT CANC RES ID TYROSINE KINASE-ACTIVITY; EGF-RECEPTOR; NEOPLASTIC PROGRESSION; SIGNAL TRANSDUCTION; NEU ONCOGENE; PROTEIN; PROLIFERATION; ALPHA; SIMILARITY; CANCER AB The role of peptide growth factors in the process of multistage carcinogenesis of rat tracheal epithelial (RTE) cells was assessed by examining growth factor requirements and expression of growth factors and their receptors in normal and transformed RTE cells. Transformed RTE cell lines show decreased requirements for bovine pituitary extract, insulin and epidermal growth factor compared to primary RTE cells in culture. An autocrine role for TGF-alpha in transformed RTE cells is suggested by data showing TGF-alpha production and decreased proliferation in the presence of TGF-alpha antisera and TGF-alpha/EGF receptor kinase inhibitor. Therefore, decreased EGF requirements in transformed RTE cells could be explained by autocrine TGF-alpha regulation. In contrast, no evidence for an insulin/IGF-I autocrine pathway could be detected in transformed RTE cells. These data indicate that multiple alterations in growth factor pathways occur in transformed RTE cells. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 28 TC 0 Z9 0 U1 0 U2 0 PU JAPAN RADIATION RESEARCH SOC PI CHIBA PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA 263, JAPAN SN 0449-3060 J9 J RADIAT RES JI J. Radiat. Res. PD DEC PY 1991 VL 32 SU 2 BP 277 EP 287 DI 10.1269/jrr.32.SUPPLEMENT2_277 PG 11 WC Biology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA JD399 UT WOS:A1991JD39900027 PM 1823364 ER PT J AU TAITELBAUM, H HAVLIN, S KIEFER, JE TRUS, B WEISS, GH AF TAITELBAUM, H HAVLIN, S KIEFER, JE TRUS, B WEISS, GH TI SOME PROPERTIES OF THE A+B-]C REACTION-DIFFUSION SYSTEM WITH INITIALLY SEPARATED COMPONENTS SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article; Proceedings Paper CT CONF ON MODELS OF NON-CLASSICAL REACTION RATES CY MAR 25-27, 1991 CL NIH, BETHESDA, MD HO NIH DE REACTION-DIFFUSION EQUATION; EXACT ENUMERATION METHOD; PERCOLATION SYSTEM; FRACTAL MEDIUM ID PARTICLE-ANTIPARTICLE ANNIHILATION; NEAREST-NEIGHBOR DISTANCES; LAMELLAR SYSTEM; REACTION FRONT; SCALING APPROACH; KINETICS; PRECIPITATION; DYNAMICS; DENSITY; TRAP AB We study some properties of the A + B --> C reaction-diffusion system with initially separated components, first analyzed by means of an asymptotic scaling argument by Galfi and Racz. We show that, in contrast to the asymptotic result that predicts that the rate of production of C goes like t-1 2, at early times it is shown to increase as t1 2. Deviations from this behavior appear at times inversely proportional to the reaction constant. Analogous crossover properties appear in the kinetic behavior of the reaction front. A second part of the study is concerned with the same chemical reaction on a fractal surface. When the substrate is a percolation cluster at criticality, both the maximum production rate and the width of the reaction zone differ considerably from those for the homogeneous space. C1 NIH,BETHESDA,MD 20892. RP TAITELBAUM, H (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. NR 27 TC 93 Z9 93 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD DEC PY 1991 VL 65 IS 5-6 BP 873 EP 891 DI 10.1007/BF01049587 PG 19 WC Physics, Mathematical SC Physics GA GY071 UT WOS:A1991GY07100005 ER PT J AU SZABO, A ZWANZIG, R AF SZABO, A ZWANZIG, R TI REVERSIBLE DIFFUSION-INFLUENCED REACTIONS - COMPARISON OF THEORY AND SIMULATION FOR A SIMPLE-MODEL SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article; Proceedings Paper CT CONF ON MODELS OF NON-CLASSICAL REACTION RATES CY MAR 25-27, 1991 CL NIH, BETHESDA, MD HO NIH DE CHEMICAL KINETICS; REVERSIBLE REACTIONS; DIFFUSION; BIMOLECULAR; MASTER EQUATION; SIMULATION ID TRAPS AB Computer simulations of a simple model of a reversible diffusion-influenced reaction are used to test various approximate theoretical treatments. The model is a random walk in continuous time of N particles on a one-dimensional lattice. The particles can be trapped reversibly at the origin. They move independently, except that only one particle at a time can occupy the origin. The theory is formulated in general terms using master equations for the probability distribution of occupancy numbers of different lattice sites. The general theoretical problem is not solved, although some exact consequences are presented. Several approximation schemes are described and tested by comparison with the simulations. RP SZABO, A (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 13 TC 48 Z9 48 U1 0 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD DEC PY 1991 VL 65 IS 5-6 BP 1057 EP 1083 DI 10.1007/BF01049598 PG 27 WC Physics, Mathematical SC Physics GA GY071 UT WOS:A1991GY07100016 ER PT J AU RICHARDS, PM SZABO, A AF RICHARDS, PM SZABO, A TI REVERSIBLE TRAPPING ON A CUBIC LATTICE - COMPARISON OF THEORY AND SIMULATIONS SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article; Proceedings Paper CT CONF ON MODELS OF NON-CLASSICAL REACTION RATES CY MAR 25-27, 1991 CL NIH, BETHESDA, MD HO NIH DE REVERSIBLE REACTIONS; SATURABLE TRAPS; BIMOLECULAR; DIFFUSION; SUPERPOSITION APPROXIMATION; CUBIC LATTICE ID DIFFUSION; TRAPS AB Simulations of the kinetics of the reversible diffusion-influenced reaction A + B reversible AB on a cubic lattice, with initial conditions [A] = [B], [AB] = 0, are compared with the predictions of two approximate theoretical formalisms. The first involves a simple rate equation with rate coefficients that are proportional to the time-dependent rate coefficient for an irreversible reaction. The second, which is based on a superposition approximation, contains a rate coefficient that explicitly depends on the bulk concentrations. Both reduce to the Smoluchowski approach in the irreversible limit. The results obtained using the modified rate equation formalism are exact at short times, but tend to approach equilibrium too rapidly. The predictions of the computationally more demanding superposition formalism agree remarkably well with the simulations for all times for the range of parameters examined. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP RICHARDS, PM (reprint author), SANDIA NATL LABS,ALBUQUERQUE,NM 87185, USA. RI Szabo, Attila/H-3867-2012 NR 19 TC 24 Z9 24 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD DEC PY 1991 VL 65 IS 5-6 BP 1085 EP 1093 DI 10.1007/BF01049599 PG 9 WC Physics, Mathematical SC Physics GA GY071 UT WOS:A1991GY07100017 ER PT J AU RUBIN, RJ AF RUBIN, RJ TI ONE-DIMENSIONAL NON-NEAREST-NEIGHBOR RANDOM-WALKS IN THE PRESENCE OF TRAPS SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article; Proceedings Paper CT CONF ON MODELS OF NON-CLASSICAL REACTION RATES CY MAR 25-27, 1991 CL NIH, BETHESDA, MD HO NIH DE ONE-DIMENSIONAL RANDOM WALK; NON-NEAREST-NEIGHBOR STEP DISTRIBUTION; TRAPS, CONDITIONED FIRST PASSAGE TIME; GENERATING FUNCTIONS AB A one-dimensional lattice random walk in the presence of m equally spaced traps is considered. The step length distribution is a symmetric exponential. An explicit analytic expression is obtained for the probability that the random walk will be trapped at the jth trapping site. RP RUBIN, RJ (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD DEC PY 1991 VL 65 IS 5-6 BP 1207 EP 1216 DI 10.1007/BF01049607 PG 10 WC Physics, Mathematical SC Physics GA GY071 UT WOS:A1991GY07100025 ER PT J AU WILLIAMSASHMAN, HG REDDI, AH AF WILLIAMSASHMAN, HG REDDI, AH TI DIFFERENTIATION OF MESENCHYMAL TISSUES DURING PHALLIC MORPHOGENESIS WITH EMPHASIS ON THE OS-PENIS - ROLES OF ANDROGENS AND OTHER REGULATORY AGENTS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review ID GENITAL TUBERCLE; BONE-DEVELOPMENT; OSTEOGENIN; PROTEIN; GROWTH; RAT; LOCALIZATION; STIMULATION; CLITORIDIS; SEQUENCE AB This article reviews various aspects of differentiation and growth of phallic mesodermal tissues with special reference to the os penis. In many species of certain mammalian orders the penile interior contains an os penis or baculum with bona fide bone. Mechanisms of phenotypic sex differentiation and the androgenic regulation of morphogenesis of genitourinary tracts of both sexes are first overviewed. Thereafter the various mesodermal tissues in fully developed penes and clitorides are discussed. The developmental fate of mesenchymal cells in the fetal genital tubercles is then considered in detail, including considerations of epithelial-mesenchymal interactions. The review concludes with a discussion of the possible roles of certain polypeptide growth factors acting in concert with androgenic steroids. Special emphasis is placed on the potential role of bone morphogenetic proteins in formation of the os penis in a restricted number of eutherian mammalian taxa. C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. UNIV CHICAGO,INST BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. NR 42 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD DEC PY 1991 VL 39 IS 6 BP 873 EP 881 DI 10.1016/0960-0760(91)90344-5 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA GY663 UT WOS:A1991GY66300001 PM 1751388 ER PT J AU SANDER, CA MEDEIROS, LJ ABRUZZO, LV HORAK, ID JAFFE, ES AF SANDER, CA MEDEIROS, LJ ABRUZZO, LV HORAK, ID JAFFE, ES TI LYMPHOBLASTIC LYMPHOMA PRESENTING IN CUTANEOUS SITES - A CLINICOPATHOLOGICAL ANALYSIS OF 6 CASES SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID T-CELL; MALIGNANT-LYMPHOMA; MONOCLONAL-ANTIBODIES; GENE REARRANGEMENT; HODGKINS-DISEASE; B-CELL; LEUKEMIA; EXPRESSION; MARKERS; TUMOR AB Six patients with malignant lymphoma of lymphoblastic type involving cutaneous sites at time of diagnosis are presented. Skin sites of the head and neck were involved in all patients and included the scalp (three patients), forehead (two patients), and malar region of the face (one patient). Two patients also had additional sites of skin disease (neck, breast, and anterior trunk). In two patients the skin was the predominant site of disease, whereas in the remaining patients staging workup revealed generalized lymphoma. The histologic findings in each patient were typical of lymphoblastic lymphoma; the neoplastic cells were small with blastic nuclear chromatin. In three patients the neoplastic cells were convoluted, and in three they were nonconvoluted. Immunophenotypically, four lymphomas were of pre-B cell type, and two lymphomas were of T cell type. There was no correlation between histologic features and the immunophenotype. Since the majority of lymphoblastic lymphomas are of T cell type, the predominance of pre-B cell tumors involving the skin may suggest that pre-B cell neoplasms have a predilection for cutaneous involvement. In further support of this hypothesis, both lymphomas that appear to have arisen in the skin had a pre-B cell immunophenotype. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N108,BETHESDA,MD 20892. NCI,LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 25 TC 55 Z9 56 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1991 VL 25 IS 6 BP 1023 EP 1031 DI 10.1016/0190-9622(91)70302-I PN 1 PG 9 WC Dermatology SC Dermatology GA GR426 UT WOS:A1991GR42600008 PM 1810981 ER PT J AU GLOWA, JR AF GLOWA, JR TI BEHAVIORAL-TOXICOLOGY OF VOLATILE ORGANIC-SOLVENTS .5. COMPARISONS OF THE BEHAVIORAL AND NEUROENDOCRINE EFFECTS AMONG NORMAL-ALKANES SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article AB Four homologous n-alkanes were compared for their ability to impair performance and stimulate hypothalamic-pituitary activity in mice. Performance was assessed using operant responding maintained under a fixed interval 60-sec schedule of milk presentation. Cumulative concentration-effect functions for octane, heptane, hexane, and pentane were obtained by incrementally increasing exposure concentrations until responding was abolished. Recovery from these rate-decreasing effects was determined 30 min after exposure to the highest concentration. Rate-decreasing potency (EC50) was greatest for octane (2474 ppm), and progressively less for heptane (3872 ppm), hexane (7051 ppm), and pentane (36130 ppm). Responding recovered completely 30 min after exposure for pentane and hexane, to 75% of pre-exposure levels for heptane, but to only 15% of pre-exposure levels for octane. The risk of obtaining a small effect with these agents (the concentration expected to decrease performance 10% in 1 out of 1000 mice) exhibited a similar order. The effect was predicted to occur at 227 ppm for octane, 331 ppm for heptane, and 1429 ppm for pentane. However, this prediction occurred at an unusually low dose for hexane (68 ppm). These n-alkanes also stimulated up to 2000-fold increases in adrenocorticotropin hormone (ACTH) release. n-Hexane was slightly more potent and produced larger effects. These studies demonstrate a direct relationship between aliphatic carbon chain length and the potency of n-alkanes in impairing performance. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 16 TC 7 Z9 7 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD DEC PY 1991 VL 10 IS 6 BP 639 EP 646 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HL655 UT WOS:A1991HL65500001 ER PT J AU KEELS, MA KASTE, LM WEINTRAUB, JA KLEINMAN, DV VERRUSIO, AC NEIDLE, EA AF KEELS, MA KASTE, LM WEINTRAUB, JA KLEINMAN, DV VERRUSIO, AC NEIDLE, EA TI A NATIONAL SURVEY OF WOMEN DENTISTS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID MERCURY; EXPOSURE AB Baseline practice pattern information was collected on all U.S. women dentists to explore the feasibility of conducting future detailed studies of specific occupational exposures in relation to health outcomes. C1 DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. UNIV N CAROLINA,SCH DENT,DEPT DENT ECOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. NIDR,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT HLTH POLICY & ADM,CHAPEL HILL,NC 27514. RP KEELS, MA (reprint author), DUKE UNIV,MED CTR,DEPT SURG,BOX 3120,DURHAM,NC 27710, USA. NR 29 TC 6 Z9 6 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 DEC PY 1991 VL 122 IS 13 BP 31 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GU759 UT WOS:A1991GU75900009 PM 1783720 ER PT J AU DANFORD, DE STEPHENSON, MG AF DANFORD, DE STEPHENSON, MG TI HEALTHY PEOPLE 2000 - DEVELOPMENT OF NUTRITION OBJECTIVES SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article C1 CTR FOOD SAFETY & APPL NUTR,OFF NUTR & FOOD SCI,FOOD & DRUG ADM,WASHINGTON,DC 20204. RP DANFORD, DE (reprint author), NIH,DIV NUTR RES COORDINAT,BETHESDA,MD 20892, USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU AMER DIETETIC ASSOC 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 DEC PY 1991 VL 91 IS 12 BP 1517 EP 1519 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GV640 UT WOS:A1991GV64000003 PM 1960341 ER PT J AU KANT, AK BLOCK, G SCHATZKIN, A ZIEGLER, RG NESTLE, M AF KANT, AK BLOCK, G SCHATZKIN, A ZIEGLER, RG NESTLE, M TI DIETARY DIVERSITY IN THE UNITED-STATES POPULATION, NHANES II, 1976-1980 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRIENT ADEQUACY; FOOD CHOICES; CHILDREN; VALIDITY; SCORE; WOMEN AB The extent of diversity in the diets of black and white adults (n = 11,658) aged 19 to 74 years was evaluated from 24-hour dietary recalls obtained in the second National Health and Nutrition Examination Survey. Each 24-hour recall was evaluated for the consumption of items from the dairy, meat, grain, fruit, and vegetable groups (Food Group Score). A second scoring method (Serving Score) evaluated every recall for consumption of at least two servings each from dairy, meat, fruit, and vegetable groups and four servings from the grain group. Only a third of the population surveyed reported consuming foods from all the food groups on the survey day; less than 3% reported consuming foods from all food groups in at least the recommended amount. Blacks scored lower on both types of diet diversity scores than whites. Both types of diversity scores showed a significant trend to increase with increasing income and level of education. Failure to consume any foods from the dairy, meat, grain, fruit, and vegetable groups was reported by 24%, 6%, 5%, 46%, and 18%, respectively, of the population on the survey day. The proportion ot the population consuming at least the desired number of servings from each of these food groups was 51%, 71%, 29%, 29%, 61%, respectively. The results emphasize the need for major public campaigns directed at increasing the diversity of US diets. Special target groups include minorities and those with limited income and formal education. C1 NCI,DIV CANC PREVENT CONTROL,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NYU,NEW YORK,NY 10003. RP KANT, AK (reprint author), CUNY QUEENS COLL,FLUSHING,NY 11367, USA. RI Block, Gladys/E-3304-2010 NR 26 TC 135 Z9 136 U1 5 U2 13 PU AMER DIETETIC ASSOC 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 DEC PY 1991 VL 91 IS 12 BP 1526 EP 1531 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GV640 UT WOS:A1991GV64000006 PM 1960344 ER PT J AU KANT, AK SCHATZKIN, A BLOCK, G ZIEGLER, RG NESTLE, M AF KANT, AK SCHATZKIN, A BLOCK, G ZIEGLER, RG NESTLE, M TI FOOD GROUP INTAKE PATTERNS AND ASSOCIATED NUTRIENT PROFILES OF THE UNITED-STATES POPULATION SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID EATING PATTERNS; DIETARY; CHILDREN; ADEQUACY; CHOICES; VARIETY; HEALTH; WOMEN; SCORE AB We developed a method for evaluating food group intake patterns using dietary recall data (n = 11,529) from the second National Health and Nutrition Examination Survey. We used this method to examine the relationship of these food group intake patterns to nutrient intake and to selected biochemical indexes of nutritional status. We evaluated each 24-hour dietary intake recall for the presence or omission of five broad food groups-dairy, meat, grain, fruit, and vegetable. The five most prevalent patterns and the proportion of the population reporting them was as follows: all food groups, 33.6%; no fruit, 23.9%; no dairy and fruit, 9.0%; no dairy, 8.0%; and no fruit and vegetable, 5.6%. In the most prevalent pattern, all food groups were consumed; this was the only pattern that provided mean amounts of all of the key vitamins and minerals at levels greater than or equal to the Recommended Dietary Allowances (RDAs). This pattern also was reported by the lowest proportion of individuals consuming less than 100% RDA of the key nutrients. Patterns in which both fruit and vegetables were consumed were associated with highest levels of serum vitamin C. The consistency of these results indicates that screening diets for food group consumption can quickly provide meaningful information about their quality. C1 NCI,BETHESDA,MD 20892. NYU,NEW YORK,NY 10003. RP KANT, AK (reprint author), CUNY QUEENS COLL,FLUSHING,NY 11367, USA. RI Block, Gladys/E-3304-2010 NR 34 TC 77 Z9 78 U1 0 U2 4 PU AMER DIETETIC ASSOC 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 DEC PY 1991 VL 91 IS 12 BP 1532 EP 1537 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GV640 UT WOS:A1991GV64000007 PM 1960345 ER PT J AU BERG, L BUCKWALTER, KC CHAFETZ, PK GWYTHER, LP HOLMES, D KOEPKE, KM LAWTON, MP LINDEMAN, DA MAGAZINER, J MASLOW, K MORLEY, JE ORY, MG RABINS, PV SLOANE, PD TERESI, J AF BERG, L BUCKWALTER, KC CHAFETZ, PK GWYTHER, LP HOLMES, D KOEPKE, KM LAWTON, MP LINDEMAN, DA MAGAZINER, J MASLOW, K MORLEY, JE ORY, MG RABINS, PV SLOANE, PD TERESI, J TI SPECIAL CARE UNITS FOR PERSONS WITH DEMENTIA SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; PROXY RESPONSE; HEALTH; PREVALENCE; IMPACT C1 UNIV IOWA,IOWA CITY,IA 52242. UNIV TEXAS,SW MED CTR,AUSTIN,TX 78712. DUKE UNIV,MED CTR,DURHAM,NC 27710. HEBREW HOME AGED,RIVERDALE,GA. PHILADELPHIA GERIATR CTR,PHILADELPHIA,PA 19141. UNIV CALIF DAVIS,DAVIS,CA 95616. UNIV MARYLAND,COLLEGE PK,MD 20742. US CONGRESS,OFF TECHNOL ASSESSMENT,WASHINGTON,DC. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63104. VET ADM MED CTR,ST LOUIS,MO 63125. NIA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. UNIV N CAROLINA,CHAPEL HILL,NC 27514. COLUMBIA UNIV,MED CTR,NEW YORK,NY 10027. RP BERG, L (reprint author), WASHINGTON UNIV,SCH MED,CAMPUS BOX 8111 ADRC,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. FU NIA NIH HHS [P50-AG05681] NR 58 TC 40 Z9 40 U1 0 U2 1 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 DEC PY 1991 VL 39 IS 12 BP 1229 EP 1236 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA GT521 UT WOS:A1991GT52100014 PM 1960368 ER PT J AU ROSTAND, SG BRUNZELL, JD CANNON, RO VICTOR, RG AF ROSTAND, SG BRUNZELL, JD CANNON, RO VICTOR, RG TI CARDIOVASCULAR COMPLICATIONS IN RENAL-FAILURE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review DE CARDIOVASCULAR COMPLICATIONS; ISCHEMIC HEART DISEASE; AUTONOMIC NEUROPATHY; LIPID ABNORMALITIES ID HEMODIALYSIS-PATIENTS; UREMIC PATIENTS; MAINTENANCE HEMODIALYSIS; LIPOPROTEIN-LIPASE; DIALYSIS PATIENTS; CORONARY RESERVE; BLOOD-PRESSURE; RENIN-ACTIVITY; HEART-DISEASE; PLASMA AB Cardiovascular diseases are a leading cause of death in end-stage renal disease (ESRD) largely as a result of the progressively increasing age of ESRD patients and the broad constellation of uremia-associated factors that can adversely affect cardiac function. Hypertension, one of the leading causes of renal failure, is a major culprit in this process, causing left ventricular hypertrophy, cardiac chamber dilation, increased left ventricular wall stress, redistribution of coronary blood flow, reduced coronary artery vasodilator reserve, ischemia, myocardial fibrosis, heart failure, and arrhythmias. In addition to impairing the coronary microcirculation, hypertension may contribute to the development of atherosclerotic coronary artery disease, particularly in the presence of the many lipid abnormalities observed in ESRD. These patients have reduced high-density lipoprotein cholesterol and increased plasma triglyceride concentrations, and there is a defect in cholesterol transport. Other abnormalities that may contribute to atherosclerotic coronary artery disease in ESRD are reduced high-density lipoprotein cholesterol synthesis and reduced activity of the reverse cholesterol pathway. Treatment with fibric acids, nicotinic acids, and lovastatin may be useful in lowering cholesterol and triglyceride concentrations in some of these patients. The incidence of coronary artery disease in ESRD populations is difficult to determine. About 25 to 30% of ESRD patients with angina have no evidence of significant coronary artery disease, and an undetermined number have silent coronary disease. The presence of resting electrocardiographic abnormalities caused by hypertension or conduction defects makes it difficult to accurately diagnosis coronary artery disease in ESRD populations by noninvasive methods, including exercise testing and thallium scintigraphy with or without the use of dipyridamole. Hypotension is a frequent complication of the dialytic process. Many factors have been implicated, including autonomic neuropathy. There is no concensus on the function of the efferent limb of the sympathetic nervous system. The afferent limb (arterial baroreflex function) is felt to be impaired. Further, there may be defects in the ability of the cardiovascular system to respond to sympathetic nerve activity. Most studies of autonomic function have used indirect measurements. Studies are underway that use techniques to assess sympathetic function directly. Such experiments with microneuropathy suggest greater skeletal sympathetic muscle discharge in uremic patients than in normal patients. C1 UNIV WASHINGTON,SCH MED,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA 98195. NHLBI,CARDIOL BRANCH,CARDIOVASC DIAG SECT,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DIV CARDIOL,DALLAS,TX 75230. RP ROSTAND, SG (reprint author), UNIV ALABAMA,DIV NEPHROL,BIRMINGHAM,AL 35294, USA. FU NIDDK NIH HHS [DK02456, 1-P50-DK-3958-3] NR 61 TC 181 Z9 181 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1991 VL 2 IS 6 BP 1053 EP 1062 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA GV914 UT WOS:A1991GV91400001 PM 1777585 ER PT J AU POGREBNIAK, HW PREWITT, TW MATTHEWS, WA PASS, HI AF POGREBNIAK, HW PREWITT, TW MATTHEWS, WA PASS, HI TI TUMOR-NECROSIS-FACTOR-ALPHA ALTERS RESPONSE OF LUNG-CANCER CELLS TO OXIDATIVE STRESS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MANGANOUS SUPEROXIDE-DISMUTASE; IMMUNOTHERAPY; INTERLEUKIN-2; INDUCTION; MECHANISM; TOXICITY AB Selected immunotherapies (tumor necrosis factor, interleukin-1, interleukin-2, and gamma interferon), chemotherapeutic agents (mitomycin, platinum, doxorubicin [Adriamycin], and bleomycin), and radiation therapy have been described to exert cytotoxicity through the generation of reactive oxygen species, including superoxide and hydrogen peroxide. Tumor necrosis factor, however, has been shown to impart increased resistance in vitro and in vivo against reactive oxygen species stress, including radiation therapy and oxygen toxicity, possibly because of the induction of increased cellular buffering capacities. It is unknown whether the sensitivity of a lung cancer cell to reactive oxygen species therapy is altered by tumor necrosis factor through the induction of free radical scavenging enzymes such as manganese superoxide dismutase. This question was investigated as follows: A549 lung adenocarcinoma cells, exposed for 24 hours to 0, 0.1, 1.0, or 10-mu-g/ml concentrations of tumor necrosis factor, were exposed to hypoxanthine plus xanthine oxidase, a superoxide generating system, for varying intervals. The number of cells surviving 5 days after the stress was determined, and cells exposed to tumor necrosis factor were examined by Northern Blot analysis for induction of the manganese superoxide dismutase gene. The hypoxanthine-xanthine oxidase stress alone caused a time-dependent decrease in survival; however, pretreatment with tumor necrosis factor increased cell survival significantly. Moreover, the cells exposed to tumor necrosis factor had a fivefold increase in the number of manganese superoxide dismutase transcripts. These findings suggest that tumor necrosis factor may confer resistance of lung cancer cells to subsequent reactive oxygen species-based therapies, and the resistance of these cells may be due to increased expression of manganese superoxide dismutase. Clinical treatment failures may result, especially if tumor necrosis factor is given concurrently with other therapies. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. RP PASS, HI (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 1991 VL 102 IS 6 BP 904 EP 907 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA GV174 UT WOS:A1991GV17400013 PM 1960995 ER PT J AU ROBINSON, RD MURPHY, EL WILKS, RJ NEVA, FA TERRY, SI HANCHARD, B FIGUEROA, JP BLATTNER, WA AF ROBINSON, RD MURPHY, EL WILKS, RJ NEVA, FA TERRY, SI HANCHARD, B FIGUEROA, JP BLATTNER, WA TI GASTROINTESTINAL PARASITIC INFECTION IN HEALTHY JAMAICAN CARRIERS OF HTLV-I SO JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VIRUS TYPE-I; STRONGYLOIDES-STERCORALIS; CARIBBEAN REGION AB A subsample (1.6%; n = 13 260) of a healthy Jamaican population of food-handlers, studied by Murphy et al. (1991), who were serologically positive (n = 99) or negative (n = 113) for HTLV-I was investigated for intestinal parasitic infection using coprological methods. Helminth infection included Ascaris lumbricoides (2.8%), Trichuris trichiura (7.1%) and hookworms (6.1%). Entamoeba coli was found in 21.8% of samples, while E. hartmanni, Giardia lamblia, Endolimax nana, Iodamoeba butschlii and Chilomastix mesnili each occurred in less than 10% of responders. T. trichiura displayed a higher prevalence (10.6 vs 3%) (chi-2 = 4.623; P = 0.03) in the HTLV-I negative group. G. lamblia was detected more frequently among HTLV-I carriers compared to controls (9.1 and 3.5%, respectively), but the association was not statistically significant (chi-2 = 2.825; P = 0.09). Infection with intestinal parasites is likely to occur independent of HTLV-I status: however, possible HTLV-I-induced immunosuppression may lead to higher intensity infections of certain organisms thus facilitating easier detection using parasitological methods. The immunomodulatory potential of HTLV-I infection in the aetiology of non-malignant diseases requires further investigation. C1 UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. UNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICA. MINIST HLTH,KINGSTON 5,JAMAICA. NIH,BETHESDA,MD 20892. RP ROBINSON, RD (reprint author), UNIV W INDIES,DEPT ZOOL,PARASITE RES LABS,KINGSTON 7,JAMAICA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0022-5304 J9 J TROP MED HYG JI J. Trop. Med. Hyg. PD DEC PY 1991 VL 94 IS 6 BP 411 EP 415 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA GV945 UT WOS:A1991GV94500009 PM 1758014 ER PT J AU MCBRIDE, AA HOWLEY, PM AF MCBRIDE, AA HOWLEY, PM TI BOVINE PAPILLOMAVIRUS WITH A MUTATION IN THE E2-SERINE 301-PHOSPHORYLATION SITE REPLICATES AT A HIGH COPY NUMBER SO JOURNAL OF VIROLOGY LA English DT Article ID CASEIN KINASE-II; EARLY REGION TRANSFORMATION; CARBOXY-TERMINAL DOMAIN; DNA-BINDING ACTIVITY; NF-KAPPA-B; MOUSE CELLS; E2 GENE; TRANSCRIPTIONAL REPRESSOR; PLASMID MAINTENANCE; TYPE-1 AB The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes at least three proteins with transcriptional regulatory properties. The full-length E2 open reading frame encodes a transcriptional transactivator, and the 3' region encodes two smaller polypeptides that repress E2-mediated transactivation. The full-length gene product is also required for viral DNA replication. We have demonstrated that the BPV-1 E2 polypeptides are phosphorylated primarily on two serine residues at a site adjacent to the carboxy-terminal DNA binding domain, which is common to all three E2 proteins (A. A. McBride, J. B. Bolen, and P. M. Howley, J. Virol. 63:5076-5085, 1989). These serine residues, at amino acid positions 298 and 301, were substituted with alanine residues in the context of the entire BPV-1 genome. The mutated BPV-1 genomes were introduced into rodent cell lines and assayed for focus formation, viral gene expression, and extrachromosomal viral DNA replication. Viral DNAs containing the E2 serine-to-alanine substitution mutants transformed C127 cells with efficiencies comparable to that of wild-type BPV-1. However, the viral genome containing the serine-to-alanine substitution at position 301 of the E2 polypeptide replicated to a copy number 20-fold higher than that of wild-type DNA. RP MCBRIDE, AA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. OI McBride, Alison/0000-0001-5607-5157 NR 50 TC 36 Z9 36 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 DEC PY 1991 VL 65 IS 12 BP 6528 EP 6534 PG 7 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800018 PM 1658358 ER PT J AU CAUGHEY, B RAYMOND, GJ ERNST, D RACE, RE AF CAUGHEY, B RAYMOND, GJ ERNST, D RACE, RE TI N-TERMINAL TRUNCATION OF THE SCRAPIE-ASSOCIATED FORM OF PRP BY LYSOSOMAL PROTEASE(S) - IMPLICATIONS REGARDING THE SITE OF CONVERSION OF PRP TO THE PROTEASE-RESISTANT STATE SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; NEURO-BLASTOMA CELLS; PRION-PROTEIN; FIBRIL PROTEIN; CULTURED-CELLS; MUSCLE-CELLS; MOUSE-BRAIN; IDENTIFICATION; INFECTIVITY; DEGRADATION AB Scrapie and related transmissible spongiform encephalopathies result in the accumulation of a protease-resistant form of an endogenous brain protein called PrP. As an approach to understanding the scrapie-associated modification of PrP, we have studied the processing and sedimentation properties of protease-resistant PrP (PrP-res) in scrapie-infected mouse neuroblastoma cells. Like brain-derived PrP-res, the neuroblastoma cell PrP-res aggregated in detergent lysates, providing evidence that the tendency to aggregate is an intrinsic property of PrP-res and not merely a secondary consequence of degenerative brain pathology. The PrP-res species had lower apparent molecular masses than the normal, protease-sensitive PrP species and were not affected by moderate treatments with proteinase K. This suggested that the PrP-res species were partially proteolyzed by the neuroblastoma cells. Immunoblot analysis of PrP-res with a panel of monospecific anti-PrP peptide sera confirmed that the PrP-res species were quantitatively truncated at the N terminus. The metabolic labeling of PrP-res in serum-free medium did not prevent the proteolysis of PrP-res, showing that the protease(s) involved was cellular rather than serum-derived. The PrP-res truncation was inhibited in intact cells by leupeptin and NH4Cl. This provided evidence that a lysosomal protease(s) was involved, and therefore, that PrP-res was translocated to lysosomes. When considered with other studies, these results imply that the conversion of PrP to the protease-resistant state occurs in the plasma membrane or along an endocytic pathway before PrP-res is exposed to endosomal and lysosomal proteases. RP CAUGHEY, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 56 TC 332 Z9 339 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 DEC PY 1991 VL 65 IS 12 BP 6597 EP 6603 PG 7 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800026 PM 1682507 ER PT J AU PHELPS, WC BAGCHI, S BARNES, JA RAYCHAUDHURI, P KRAUS, V MUNGER, K HOWLEY, PM NEVINS, JR AF PHELPS, WC BAGCHI, S BARNES, JA RAYCHAUDHURI, P KRAUS, V MUNGER, K HOWLEY, PM NEVINS, JR TI ANALYSIS OF TRANSACTIVATION BY HUMAN PAPILLOMAVIRUS TYPE-16 E7 AND ADENOVIRUS-12S E1A SUGGESTS A COMMON MECHANISM SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING ACTIVITY; RETINOBLASTOMA GENE-PRODUCT; CERVICAL-CARCINOMA CELLS; E2F TRANSCRIPTION FACTOR; E4 GENE; MUTATIONAL ANALYSIS; HUMAN KERATINOCYTES; FUNCTIONAL DOMAINS; TRANSFORMING GENE; ESCHERICHIA-COLI AB The human papillomavirus E7 gene product is an oncoprotein with properties similar to those of the adenovirus E1A proteins. The human papillomavirus E7 proteins possess substantial amino acid sequence similarity to portions of conserved regions 1 and 2 of E1A, and the human papillomavirus type 16 E7 protein trans-activates the adenovirus E2 early promoter. Analysis of point mutations in the E2 promoter indicated that the E2F recognition sites were critical to E7 stimulation. In contrast to the activation of the E2 promoter, E7 could not trans-activate various other E1A-inducible promoters. Although the promoter specificity for E7 differs from that of 13S E1A trans activation, it is very similar to activation by the E1A 12S product. Moreover, analysis of the E7 protein has suggested that amino acid sequences critical for trans activation include those shared with E1A within conserved region 2. Biochemical studies demonstrate that the E7 protein, like the 12S E1A product, can alter the interaction of cellular factors with the E2F transcription factor. We therefore conclude that E7 trans activation is functionally related to that mediated by the 12S E1A product. C1 DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,GENET SECT,DURHAM,NC 27710. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RP PHELPS, WC (reprint author), BURROUGHS WELLCOME CO,DIV VIROL,RES TRIANGLE PK,NC 27709, USA. OI Munger, Karl/0000-0003-3288-9935 FU NIGMS NIH HHS [GM 26765] NR 67 TC 106 Z9 108 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 DEC PY 1991 VL 65 IS 12 BP 6922 EP 6930 PG 9 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800063 PM 1834862 ER PT J AU DERSE, D CARVALHO, M CARROLL, R PETERLIN, BM AF DERSE, D CARVALHO, M CARROLL, R PETERLIN, BM TI A MINIMAL LENTIVIRUS TAT SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; HIV-1 TAT; TRANS-ACTIVATION; ANTI-TERMINATION; NUCLEAR-PROTEIN; GENE-PRODUCT; PHAGE-LAMBDA; RNA; TRANSCRIPTION AB Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop. C1 UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NR 27 TC 70 Z9 71 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1991 VL 65 IS 12 BP 7012 EP 7015 PG 4 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800076 PM 1658392 ER PT J AU OVERBAUGH, J RUDENSEY, LM PAPENHAUSEN, MD BENVENISTE, RE MORTON, WR AF OVERBAUGH, J RUDENSEY, LM PAPENHAUSEN, MD BENVENISTE, RE MORTON, WR TI VARIATION IN SIMIAN IMMUNODEFICIENCY VIRUS ENV IS CONFINED TO V1 AND V4 DURING PROGRESSION TO SIMIAN AIDS SO JOURNAL OF VIROLOGY LA English DT Note ID ENVELOPE GENE; HTLV-III; REVERSE-TRANSCRIPTASE; MACROPHAGE TROPISM; RECEPTOR-BINDING; VARIABLE REGIONS; VIRAL ENVELOPE; CD4 RECEPTOR; T-CELL; TYPE-1 AB We have monitored changes in the simian immunodeficiency virus (SIV) envelope (env) gene in two macaques which developed AIDS after inoculation with a molecular clone of SIV. As the animals progressed to AIDS, selection occurred for viruses with variation in two discrete regions (V1 and V4) but not for viruses with changes in the region of SIV env that corresponds to the immunodominant, V3 loop of human immunodeficiency virus. Within the highly variable domains, the vast majority of nucleotide changes encoded an amino acid change (98%), suggesting that these envelope variants had evolved as a result of phenotypic selection. Analysis of the biological properties of these variants, which have been selected for in the host, may be useful in defining the mechanisms underlying viral persistence and progression to simian AIDS. C1 UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP OVERBAUGH, J (reprint author), UNIV WASHINGTON,DEPT MICROBIOL,SC-42,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI26503] NR 37 TC 181 Z9 181 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 DEC PY 1991 VL 65 IS 12 BP 7025 EP 7031 PG 7 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800079 PM 1942255 ER PT J AU YOSHIMOTO, K ROSENFELD, S FRICKHOFEN, N KENNEDY, D HILLS, R KAJIGAYA, S YOUNG, NS AF YOSHIMOTO, K ROSENFELD, S FRICKHOFEN, N KENNEDY, D HILLS, R KAJIGAYA, S YOUNG, NS TI A 2ND NEUTRALIZING EPITOPE OF B19-PARVOVIRUS IMPLICATES THE SPIKE REGION IN THE IMMUNE-RESPONSE SO JOURNAL OF VIROLOGY LA English DT Note ID B19 PARVOVIRUS INFECTION; HYDROPS FETALIS; ANEMIA; VIRUS; ANTIBODIES; PROTEINS; CULTURES; CRISIS AB We used 18 monoclonal antibodies against B19 parvovirus to identify neutralizing epitopes on the viral capsid. Of the 18 antibodies, 9 had in vitro neutralizing activity in a bone marrow colony culture assay. The overlapping polypeptide fragments spanning the B19 structural proteins were produced in a pMAL-c Escherichia coli expression system and used to investigate the binding sites of the neutralizing antibodies. One of the nine neutralizing antibodies reacted with both VP1 and VP2 capsid proteins and a single polypeptide fragment on an immunoblot, identifying a linear neutralizing epitope between amino acids 57 and 77 of the VP2 capsid protein. Eight of nine neutralizing antibodies failed to react with either of the capsid proteins or any polypeptide fragments, despite reactivities with intact virions in a radioimmunoassay, suggesting that additional conformationally dependent neutralizing epitopes exist. C1 NATL HEART LUNG & BLOOD INST,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. BUR BIOLOG,DRUGS DIRECTORATE,OTTAWA K1A 0L2,ONTARIO,CANADA. BUR CHEM SAFETY,FOOD DIRECTORATE,OTTAWA K1A 0L2,ONTARIO,CANADA. NR 21 TC 46 Z9 47 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 DEC PY 1991 VL 65 IS 12 BP 7056 EP 7060 PG 5 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800085 PM 1719240 ER PT J AU KHAN, AS GALVIN, TA LOWENSTINE, LJ JENNINGS, MB GARDNER, MB BUCKLER, CE AF KHAN, AS GALVIN, TA LOWENSTINE, LJ JENNINGS, MB GARDNER, MB BUCKLER, CE TI A HIGHLY DIVERGENT SIMIAN IMMUNODEFICIENCY VIRUS (SIVSTM) RECOVERED FROM STORED STUMP-TAILED MACAQUE TISSUES SO JOURNAL OF VIROLOGY LA English DT Note ID LENTIVIRUS; RETROVIRUS; MANGABEYS; AIDS AB We report here the results of molecular analysis of a simian immunodeficiency virus (designated SIV(stm)) which was isolated from a rhesus monkey inoculated with stored lymph node tissue of an Asian stump-tailed macaque. The latter monkey had died in 1977 during an epidemic of acquired immunodeficiency and lymphoma at the California Regional Primate Research Center (L. J. Lowenstine, N. W. Lerche, P. A. Marx, M. B. Gardner, and N. C. Pedersen, p. 174-176, in M. Girard and L. Valette, ed., Retroviruses of Human AIDS and Related Animal Viruses, 1988). Nucleotide sequence analysis of the gag and env regions indicates that SIV(stm) is an ancient member of the SIV/human immunodeficiency virus type 2 group; it is quite divergent from known SIVs isolated from African sooty mangabeys as well as from Asian macaques. Furthermore, of all SIV strains described to date, SIV(stm) is the most closely related to human immunodeficiency virus type 2. C1 UNIV CALIF DAVIS,CALIF PRIMATE RES CTR,SCH VET SCI,DEPT PATHOL,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH MED,DEPT MED PATHOL,DAVIS,CA 95616. RP KHAN, AS (reprint author), NIAID,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1991 VL 65 IS 12 BP 7061 EP 7065 PG 5 WC Virology SC Virology GA GP878 UT WOS:A1991GP87800086 PM 1942258 ER PT J AU HIRAOKAYOSHIMOTO, M HIGASHIDA, K TAKEDA, M KAWAMOTO, S ICHIKAWA, I HOOVER, RL AF HIRAOKAYOSHIMOTO, M HIGASHIDA, K TAKEDA, M KAWAMOTO, S ICHIKAWA, I HOOVER, RL TI CHARACTERIZATION OF MYOSIN HEAVY AND LIGHT-CHAINS IN CULTURED MESANGIAL CELLS SO KIDNEY INTERNATIONAL LA English DT Article ID VASCULAR SMOOTH-MUSCLE; RAT GLOMERULAR CELLS; ANGIOTENSIN-II; EXPRESSION; CONTRACTION; PHOSPHORYLATION; RECEPTORS; VASOPRESSIN; ACTOMYOSIN; HORMONES AB Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that postconfluent mesangial cells in primary culture expressed three myosin heavy chains (MHCs), 204 kD, 200 kD and 196 kD, in a manner similar to that of smooth muscle cells. The MHCs of 204 kD and 200 kD in mesangial cells reacted positively with antibodies raised against bovine aorta smooth muscle myosin while the 1% kD MHC reacted positively with antibodies against platelet myosin. Moreover, the combined content of the MHCs in cultured mesangial cells was remarkably similar in amount to that in cultured aortic smooth muscle cells. After three passages, cultured mesangial cells expressed only the 196 kD MHC as has been reported for cultured smooth muscle cells. Two phosphorylated proteins were found in the immunoprecipitate after incubation of the cell extract with antibodies against platelet myosin: a MHC of approximately 200 kD and myosin light chain (MLC) of 20 kD. The level of MLC phosphorylation was quantitated by scanning densitometry of autoradiograms. Arginine vasopressin (AVP) at 100 nm induced MLC phosphorylation with a maximum effect at 10 minutes. AVP enhanced MLC phosphorylation in a dose dependent manner: maximum response was observed with 100 nM and half maximum, at 3.5 nM. Similarly, angiotensin II (100 nM), endothelin-1 (10 nM) and the calcium ionophore, A23187 (1-mu-M), significantly enhanced MLC phosphorylation. Thus, although the expression of MHC was altered in quality after mesangial cells were placed in culture, the cells remained rich in myosin content and had an intact regulatory system for contraction which responded to a variety of vasoconstrictive agents. These findings support the notion that mesangial cells have contractile capability comparable to that of smooth muscle cells. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RP HIRAOKAYOSHIMOTO, M (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT PEDIAT,DIV PEDIAT NEPHROL,C-4204,MCN,21ST & GARLAND AVE,NASHVILLE,TN 37232, USA. FU NHLBI NIH HHS [HL-14192]; NIDDK NIH HHS [DK-37869, DK-37868] NR 38 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1991 VL 40 IS 6 BP 1013 EP 1019 DI 10.1038/ki.1991.309 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA GQ259 UT WOS:A1991GQ25900004 PM 1762302 ER PT J AU ANDERSON, J BRIEFEL, G JONES, JM RYU, JH MCGUIRE, M YUN, YP AF ANDERSON, J BRIEFEL, G JONES, JM RYU, JH MCGUIRE, M YUN, YP TI EFFECTS OF ACETATE DIALYSATE ON TRANSFORMING GROWTH-FACTOR BETA-1, INTERLEUKIN, AND BETA-2-MICROGLOBULIN PLASMA-LEVELS SO KIDNEY INTERNATIONAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BIFUNCTIONAL REGULATOR; EXTRACELLULAR-MATRIX; CYTOKINE PRODUCTION; COLLAGEN FORMATION; HUMAN-MONOCYTES; SODIUM-ACETATE; MESSENGER-RNA; RENAL-DISEASE AB To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1-alpha, IL-1-beta, IL-6), TNF-alpha, TGF-beta-1, and beta-2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF-beta-1, was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF-beta-1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P < 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P < 0. 10). Acutely. TGF-beta-1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70.52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57. 43 to 69 pg/ml; P < 0.05). beta-2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM VS. 1.05 mmol +/- 0.07 SEM; P < 0.05). Inflammatory cytokines may, therefore, not be detectable with standard ELISA assays even after HD. TGF-beta-1, which stimulates extracellular matrix and collagen synthesis and modulates other cytokines, could affect the progression of CRF and combined with acetate's possible effects on phosphate kinetics, could play a role in ectopic calcifications and renal bone disease. Finally, no effect of acetate on beta-2-microglobulin levels was found. C1 NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852. RP ANDERSON, J (reprint author), JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,DIV RENAL,4940 EASTERN AVE,B2N,BALTIMORE,MD 21224, USA. NR 61 TC 29 Z9 31 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1991 VL 40 IS 6 BP 1110 EP 1117 DI 10.1038/ki.1991.322 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA GQ259 UT WOS:A1991GQ25900017 PM 1762311 ER PT J AU HERRING, JM FORTMAN, JD ANDERSON, RJ BENNETT, BT AF HERRING, JM FORTMAN, JD ANDERSON, RJ BENNETT, BT TI ULTRASONIC DETERMINATION OF FETAL PARAMETERS IN BABOONS (PAPIO-ANUBIS) SO LABORATORY ANIMAL SCIENCE LA English DT Article ID MACAQUE MACACA-FASCICULARIS; PRENATAL GROWTH; EARLY-PREGNANCY; MULATTA; CYNOMOLGUS; RHESUS AB The use of nonhuman primates to study reproductive physiology, fetal development, and neonatal management often depends on the availability of pregnant and fetal animals of known gestational history. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in olive baboons (Papio anubis). Normal cycling females were bred to proven males by using the degree of perineal swelling and vaginal cytology to determine onset of ovulation. The subjects were evaluated to determine pregnancy beginning 18 days postmating, using an Aloka-650 diagnostic ultrasound unit, equipped with a 7.5 mHz prostate probe and a 5 mHz transabdominal probe. Ten pregnant animals were then evaluated sonographically every 3 days through day 30 and weekly through day 135 (average gestation 184 days). Measurements included gestational sac, greatest-length, biparietal diameter, femur length, head circumference, and abdominal circumference. Using the means and standard deviations, growth curves were constructed, and the data used to develop predicted value charts for gestational age estimation. Using the predicted value charts established in our study, subsequent evaluation of pregnant baboons in our colony disclosed concordance with actual gestational age. C1 UNIV ILLINOIS,BIOL RESOURCES LAB,CHICAGO,IL 60612. UNIV ILLINOIS,SCH PUBL HLTH,EPIDEMIOL & BIOSTAT PROGRAM,CHICAGO,IL 60612. RP HERRING, JM (reprint author), NCI,FREDERICK CANC DEV RES CTR,PROGRAM RESOURCES INC,POB B,BLDG 429,FREDERICK,MD 21702, USA. FU NCRR NIH HHS [RR 04925-01, RR 07037-03] NR 11 TC 26 Z9 28 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1991 VL 41 IS 6 BP 602 EP 605 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HG813 UT WOS:A1991HG81300015 PM 1667206 ER PT J AU FELIX, CA POPLACK, DG AF FELIX, CA POPLACK, DG TI CHARACTERIZATION OF ACUTE LYMPHOBLASTIC-LEUKEMIA OF CHILDHOOD BY IMMUNOGLOBULIN AND T-CELL RECEPTOR GENE PATTERNS SO LEUKEMIA LA English DT Review ID MINIMAL RESIDUAL DISEASE; BETA-CHAIN GENE; PRE-B-CELLS; HUMAN LYMPHOID NEOPLASMS; ANTIGEN RECEPTOR; GAMMA-CHAIN; MONOCLONAL-ANTIBODY; INVITRO AMPLIFICATION; JUNCTIONAL DIVERSITY; PRECURSOR LEUKEMIA AB Molecular biological studies of immunoglobulin (Ig) and T-cell antigen receptor (TCR) genes provide novel approaches to the identification and characterization of the acute lymphoblastic leukemias (ALL). Such studies greatly enhance our understanding of both the cells of origin in these diseases and the order of assembly of immune receptor genes in B-cells and T-cells. The patterns of Ig and TCR genes in B-cell precursor and T-cell ALL of childhood and ALL of infancy are heterogeneous though generally distinctive. The vast majority of cases of B-cell precursor ALL of childhood rearrange Ig heavy (H) chain genes, and 40-50% rearrange Ig light (L) chain genes. In contrast, in ALL of infancy, Ig genes are frequently germline, indicating generally less mature cells of origin in younger patients. Similarly, the vast majority of cases of T-cell ALL of childhood rearrange TCR delta, gamma, and beta-genes and approximately one-half rearrange TCR-alpha. TCR gene rearrangements are very common in cases of B-cell precursor ALL, but in patterns different from T-cells. In contrast, T ALL cells only infrequently rearrange Ig genes, and TCR gamma-rearrangements are not found in ALL of infancy. The demonstration of lineage non-restricted Ig and TCR gene rearrangements raises questions about lymphocyte development and about the 'precursor' nature of ALL. The identification of generally distinctive patterns of these genes creates a foundation for their utilization as markers of minimal and preclinical disease. The extent to which specific immune receptor gene patterns correlate with clinical outcome in ALL warrants further study. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 86 TC 24 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1991 VL 5 IS 12 BP 1015 EP 1025 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA HC509 UT WOS:A1991HC50900001 PM 1837810 ER PT J AU TSAI, WP HIROSE, K NARA, PL KUANG, YD CONLEY, S LI, BQ KUNG, HF MATSUSHIMA, K AF TSAI, WP HIROSE, K NARA, PL KUANG, YD CONLEY, S LI, BQ KUNG, HF MATSUSHIMA, K TI DECREASE IN CYTOKINE PRODUCTION BY HIV-INFECTED MACROPHAGES IN RESPONSE TO LPS-MEDIATED ACTIVATION SO LYMPHOKINE AND CYTOKINE RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; NEUTROPHIL CHEMOTACTIC FACTOR; AIDS-RELATED COMPLEX; HTLV-III LAV; FACTOR-ALPHA; MONONUCLEAR PHAGOCYTES; TNF-ALPHA; MONOCYTES MACROPHAGES; BLOOD MONOCYTES AB The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1-alpha (IL-1-alpha), IL-1-beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1-beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1-alpha, IL-1-beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RES INST,DEPT PHARMACOL,KANAZAWA 920,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,TUMOR CELL BIOL LAB,FREDERICK,MD 21702. RP TSAI, WP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DCT,BRMP,PHYSIOL BIOCHEM LB,POB B,BLDG 560,RM 31-71,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 70 TC 25 Z9 25 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0277-6766 J9 LYMPHOKINE CYTOK RES JI Lymphokine Cytokine Res. PD DEC PY 1991 VL 10 IS 6 BP 421 EP 429 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA HC395 UT WOS:A1991HC39500001 PM 1725130 ER PT J AU YANG, JC SCHWARZ, SL PERRYLALLEY, DM ROSENBERG, SA AF YANG, JC SCHWARZ, SL PERRYLALLEY, DM ROSENBERG, SA TI MURINE STUDIES USING POLYETHYLENE GLYCOL-MODIFIED RECOMBINANT HUMAN INTERLEUKIN 2 (PEG-IL-2) - ANTITUMOR EFFECTS OF PEG-IL2 ALONE AND IN COMBINATION WITH ADOPTIVE CELLULAR TRANSFER SO LYMPHOKINE AND CYTOKINE RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; NECROSIS FACTOR-ALPHA; HEPATIC METASTASES; ADVANCED CANCER; LAK CELLS; LONG-TERM; IMMUNOTHERAPY; INVIVO AB A polyethylene glycol-modified form of recombinant human IL-2 (PEG-IL-2) was tested for murine antitumor effects in vitro and in vivo. This PEG-IL-2 was demonstrated to retain the in vitro ability to support T cell proliferation, enhance a mixed lymphocyte reaction, and generate lymphokine-activated killer (LAK) cells. It was found to have a circulating half-life in mice 25 times longer than unmodified recombinant IL-2 (RIL-2). Serum levels were detected up to 60 h after a single intravenous injection. When given as a single, intravenous administration the antitumor effect of this material was similar to multiple, repeated bolus doses of RIL-2. PEG-IL-2 was also found to support the in vivo efficacy of adoptively transferred LAK cells and tumor infiltrating lymphocytes (TIL). Using a congenic TIL (Thy 1.1), persistence of adoptively transferred TIL was found to be prolonged with PEG-IL-2 compared to repeated boluses of RIL-2. Four days after transfer, twice as many Thy 1.1 TIL were recoverable from the lungs of mice given PEG-IL-2. These studies show that PEG-IL-2 is a modified lymphokine with significant antitumor activity in murine systems and is superior to bolus RIL-2 in enhancing the survival of adoptively transferred TIL. RP YANG, JC (reprint author), NCI,SURG BRANCH,ROOM 2B-37,BLDG 10,BETHESDA,MD 20892, USA. NR 30 TC 10 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0277-6766 J9 LYMPHOKINE CYTOK RES JI Lymphokine Cytokine Res. PD DEC PY 1991 VL 10 IS 6 BP 475 EP 480 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA HC395 UT WOS:A1991HC39500008 PM 1804310 ER PT J AU FRANK, JA CHOYKE, PL AUSTIN, HA GIRTON, ME AF FRANK, JA CHOYKE, PL AUSTIN, HA GIRTON, ME TI FUNCTIONAL MR OF THE KIDNEY SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT WORKSHOP ON CONTRAST ENHANCED MAGNETIC RESONANCE CY MAY 23-25, 1991 CL NAPA, CA SP SOC MAGNET RESONANCE MED, ADV MAGNET, BERLEX, BRACCO, GE, GEURBET, EASTMAN KODAK, NYCOMED, SQUIBB, STERLING WINTHROP ID DYNAMIC GD-DTPA; RENAL-FUNCTION C1 GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BETHESDA,MD. RP FRANK, JA (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 10 TC 47 Z9 48 U1 0 U2 0 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 DEC PY 1991 VL 22 IS 2 BP 319 EP 323 DI 10.1002/mrm.1910220233 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GV211 UT WOS:A1991GV21100024 PM 1812364 ER PT J AU FOUTS, JR PIVER, WT AF FOUTS, JR PIVER, WT TI HUMAN HEALTH-EFFECTS AND GLOBAL CLIMATE CHANGE SO MARINE TECHNOLOGY SOCIETY JOURNAL LA English DT Article ID ULTRAVIOLET-RADIATION; RESPIRABLE AEROSOLS; NITROGEN-DIOXIDE; UNITED-STATES; RAT LUNGS; OZONE; ACID; AIR; MORTALITY; SCIENCE AB The implications for human health from global climate change are presented. Major human health hazards that may occur include the following: an increase in air pollution related disease, especially lung disease in children, elderly, and people with pre-existing chronic lung disease; an increase in bioavailability and mobility of toxic metals as related to acid rain; possible increases in vector-borne disease into new geographic locations; an increase in the frequency and severity of skin cancers and eye diseases from stratospheric ozone depletion and increased UV; changes in biodiversity that impact medical research and treatment development; and the appearance of human health hazards from attempts to mitigate global climate change, for example, CFC replacement chemicals, alternative fuels, solar energy components, and increased use of nuclear energy. RP FOUTS, JR (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 41 TC 1 Z9 1 U1 2 U2 5 PU MARINE TECHNOLOGY SOC INC PI WASHINGTON PA C/O I CLAYION MATTHEWS, 1828 L ST, NW, 9TH FL, WASHINGTON, DC 20036 SN 0025-3324 J9 MAR TECHNOL SOC J JI Mar. Technol. Soc. J. PD WIN PY 1991 VL 25 IS 4 BP 38 EP 44 PG 7 WC Engineering, Ocean; Oceanography SC Engineering; Oceanography GA HG985 UT WOS:A1991HG98500006 ER PT J AU RIPAMONTI, U MAGAN, A MA, S VANDENHEEVER, B MOEHL, T REDDI, AH AF RIPAMONTI, U MAGAN, A MA, S VANDENHEEVER, B MOEHL, T REDDI, AH TI XENOGENEIC OSTEOGENIN, A BONE MORPHOGENETIC PROTEIN, AND DEMINERALIZED BONE MATRICES, INCLUDING HUMAN, INDUCE BONE DIFFERENTIATION IN ATHYMIC RATS AND BABOONS SO MATRIX LA English DT Article DE ALKALINE PHOSPHATASE; ATHYMIC RODENTS; BONE INDUCTION; BONE MATRIX; OSTEOGENIN; PRIMATES ID EXTRACELLULAR-MATRIX; DELIVERY AB Subcutaneous implantation of xenogeneic demineralized bone matrix does not initiate endochondral bone differentiation. Dissociative extraction in 4 M guanidine-HCI or 6 M urea has shown that the apparent species-specificity of intact bone matrix resides in its insoluble immunogenic component, since there is homology in solubilized osteogenic proteins amongst mammals. To further investigate the species-specificity and cross-species reactivity of bone matrix components, baboon and human demineralized bone matrix (DBM) and bovine osteogenin, purified greater than 50 000-fold and with an apparent molecular mass of 28 -42 kilodaltons, were implanted in the subcutaneous space of athymic and euthymic rats and into the rectus abdominis of 16 baboons (Papio ursinus). Baboon DBM was also implanted in athymic and euthymic mice. Alkaline phosphatase activity and histology of implants harvested at day 11 and 30 showed that baboon and human DBM induced endochondral bone differentiation both in athymic rats and baboons. Bovine osteogenin in conjunction with baboon insoluble collagenous matrix induced extensive bone differentiation in athymic rats and baboons. Baboon and human DBM did not induce bone differentiation in euthymic rats and, in athymic mice, baboon DBM failed to induce bone differentiation, determining instead the recruitment of multinucleated giant cells. The results indicate that in rodents bone differentiation induced by intact bone matrix is species specific and that T-cell functions are not a requirement for bone induction, although immunologically competent rats block bone differentiation from xenogeneic matrix. Bone differentiation induced by human DBM in baboons suggests that intact bone matrices may not be species-specific amongst primates. These findings, by demonstrating bone induction in nonhuman primates using bovine osteogenin and intact human bone matrix, may help to design alternative osteogenic delivery systems other than allogeneic collagenous matrix for craniofacial and orthopedic applications in man. C1 UNIV WITWATERSRAND,DEPT GEN ANAT,JOHANNESBURG 2001,SOUTH AFRICA. NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. RP RIPAMONTI, U (reprint author), UNIV WITWATERSRAND,MRC,DENT RES INST,JOHANNESBURG 2001,SOUTH AFRICA. NR 30 TC 31 Z9 31 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0934-8832 J9 MATRIX JI Matrix PD DEC PY 1991 VL 11 IS 6 BP 404 EP 411 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV048 UT WOS:A1991GV04800005 PM 1787832 ER PT J AU REYNOLDS, K MEZEY, E ZIMMER, A AF REYNOLDS, K MEZEY, E ZIMMER, A TI ACTIVITY OF THE BETA-RETINOIC ACID RECEPTOR PROMOTER IN TRANSGENIC MICE SO MECHANISMS OF DEVELOPMENT LA English DT Article DE RETINOIC ACID; LACZ; TRANSGENIC MOUSE; GENE REGULATION; DEVELOPMENT ID EMBRYONAL CARCINOMA-CELLS; HEPATOCELLULAR-CARCINOMA; DIFFERENTIAL EXPRESSION; AXONAL GUIDANCE; HOMEOBOX GENES; GAMMA; IDENTIFICATION; MOUSE; MORPHOGENESIS; MALFORMATIONS AB LacZ reporter gene constructs were used to analyze the murine retinoic acid receptor beta (mRAR-beta) gene promoter in transgenic mice. LacZ expression in transgenic mouse embryos with 250 bp of promoter sequences closely parallels that of RAR-beta between embryonic days 8.5 and 12.5. This indicates that the -1 to -250 promoter region contains most regulatory elements required for tissue specific expression. Additional elements in the -250 to -625 region are required for high expression levels after day 12.5. Elements in the -625 to -3100 region are necessary to reproduce the RAR-beta expression in the meninges and the eye mesenchyme. The expression pattern of the transgene and the endogenous RAR-beta, as revealed by in situ hybridization, suggests an important role of the RAR-beta in the developing nervous system. C1 NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892. RI Zimmer, Andreas/B-8357-2009 NR 46 TC 66 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1991 VL 36 IS 1-2 BP 15 EP 29 DI 10.1016/0925-4773(91)90068-H PG 15 WC Developmental Biology SC Developmental Biology GA HC643 UT WOS:A1991HC64300002 PM 1664231 ER PT J AU BURDON, T WALL, RJ SHAMAY, A SMITH, GH HENNIGHAUSEN, L AF BURDON, T WALL, RJ SHAMAY, A SMITH, GH HENNIGHAUSEN, L TI OVER-EXPRESSION OF AN ENDOGENOUS MILK PROTEIN GENE IN TRANSGENIC MICE IS ASSOCIATED WITH IMPAIRED MAMMARY ALVEOLAR DEVELOPMENT AND A MILCHLOS PHENOTYPE SO MECHANISMS OF DEVELOPMENT LA English DT Article DE WHEY ACIDIC PROTEIN; MAMMARY GLAND; TRANSGENIC MOUSE; DEVELOPMENT; MILCHLOS; GENE EXPRESSION ID HIGH-LEVEL EXPRESSION; WHEY ACIDIC PROTEIN; TISSUE PLASMINOGEN-ACTIVATOR; GROWTH FACTOR-BETA; FUNCTIONAL-DIFFERENTIATION; CASEIN GENE; MOUSE MILK; GLAND; PROMOTER; CLONING AB The whey acidic protein (WAP) gene is expressed in mammary epithelial cells at late pregnancy and throughout lactation. We have generated transgenic mice in which a mouse WAP transgene is expressed precociously in pregnancy. From 13 founder mice bearing WAP transgenes, two female founders and the daughters from a male founder failed to lactate and nurture their offspring. We named this phenotype milchlos. Mammary tissue from postpartum milchlos mice was underdeveloped, contained too few alveoli and resembled the glands of non-transgenic mid-pregnant mice. The hypothesis that alveolar development in milchlos mice was functionally arrested in a prelactational state is consistent with low levels of alpha-lactalbumin mRNA, and an unidentified keratin RNA in mammary tissue from postpartum mice. Defects in alveolar function in milchlos mice were detected at mid-pregnancy; in non-transgenic mice, WAP was secreted into the alveolar lumen but remained preferentially in the cytoplasm of the alveolar epithelial cells in the milchlos mice. Since deregulated WAP expression resulted in impaired mammary development, it is possible that WAP plays a regulatory role in the terminal differentiation and development of mammary alveolar cells. C1 NIH,BIOCHEM & METAB LAB,BLDG 10,RM 9N113,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. USDA ARS,BELTSVILLE AGR RES CTR,REPROD LAB,BELTSVILLE,MD 20705. NR 31 TC 60 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1991 VL 36 IS 1-2 BP 67 EP 74 DI 10.1016/0925-4773(91)90073-F PG 8 WC Developmental Biology SC Developmental Biology GA HC643 UT WOS:A1991HC64300007 PM 1782141 ER PT J AU ROSEN, LN LIVINGSTONE, IR ROSENTHAL, NE AF ROSEN, LN LIVINGSTONE, IR ROSENTHAL, NE TI MULTIPLE-SCLEROSIS AND LATITUDE - A NEW PERSPECTIVE ON AN OLD ASSOCIATION SO MEDICAL HYPOTHESES LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; UNITED-STATES VETERANS; GEOGRAPHIC-DISTRIBUTION; EPIDEMIOLOGY; VIRUS AB For 68 years latitude has been identified as an important risk factor in the occurrence of multiple sclerosis (MS), but no satisfactory explanation has been offered for this relationship. Epidemiological studies of MS, however, have failed to take into account the degree of change in the amount of ambient light over the course of the year, a variable which is closely related to photoperiod and latitude. Seasonal affective disorder (SAD), another illness for which latitude is a risk factor, appears to be related to the decrease in ambient light during the winter months, and offers some relevant insights into the geographical distribution of risk for developing MS. Researchers have found a relationship between degree of reported seasonal difficulties in a population sample and altered immunological function. Furthermore, the effects of bright light on mood have been shown to be regulated through the eye. We hypothesize that the risk of developing MS is related to impairment of the immune system caused by light deprivation prior to adulthood. C1 NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT SERV UNIT,9000 ROCKVILLE PIKE,BETHESDA,MD 20814. NR 24 TC 14 Z9 14 U1 1 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD DEC PY 1991 VL 36 IS 4 BP 376 EP 378 DI 10.1016/0306-9877(91)90014-P PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HC118 UT WOS:A1991HC11800014 PM 1809858 ER PT J AU LUDLOW, CL AF LUDLOW, CL TI CHARACTERISTICS AND TREATMENT OF LARYNGEAL DYSTONIAS AFFECTING VOICE USERS SO MEDICAL PROBLEMS OF PERFORMING ARTISTS LA English DT Article RP LUDLOW, CL (reprint author), NIDOCD,VOICE & SPEECH SECT,BLDG 10,ROOM 5D38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0885-1158 J9 MED PROBL PERFORM AR JI Med. Probl. Perform. Artist. PD DEC PY 1991 VL 6 IS 4 BP 128 EP 131 PG 4 WC Medicine, General & Internal; Music SC General & Internal Medicine; Music GA GV750 UT WOS:A1991GV75000005 ER PT J AU COLE, RA COHEN, LG HALLETT, M AF COLE, RA COHEN, LG HALLETT, M TI TREATMENT OF MUSICIANS CRAMP WITH BOTULINUM TOXIN SO MEDICAL PROBLEMS OF PERFORMING ARTISTS LA English DT Article C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NR 0 TC 28 Z9 28 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0885-1158 J9 MED PROBL PERFORM AR JI Med. Probl. Perform. Artist. PD DEC PY 1991 VL 6 IS 4 BP 137 EP 143 PG 7 WC Medicine, General & Internal; Music SC General & Internal Medicine; Music GA GV750 UT WOS:A1991GV75000007 ER PT J AU MOWATT, MR AGGARWAL, A NASH, TE AF MOWATT, MR AGGARWAL, A NASH, TE TI CARBOXY-TERMINAL SEQUENCE CONSERVATION AMONG VARIANT-SPECIFIC SURFACE-PROTEINS OF GIARDIA-LAMBLIA SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE GIARDIA-LAMBLIA; ANTIGENIC VARIATION; VARIANT-SPECIFIC SURFACE PROTEIN; CYSTEINE-RICH PROTEIN ID ANTIGENIC VARIATION; GEL-ELECTROPHORESIS; MESSENGER-RNAS; DNA; LIBRARIES; INSITU; GENES; ACID AB Antigenic variation in the parasitic protozoan Giardia lamblia was studied by characterizing the expression and genomic organization of a variant-specific surface protein (VSP) gene. Transcripts from this gene, vsp1267, were abundant in the cloned variant WB/1267, but undetectable in the parental clone from which WB/1267 was derived or in variant progeny of WB/1267. Two identical copies of vsp 1267 exist in the WB/1267 genome, separated by 3 kb and arranged as convergent transcription units. Primer extension sequencing and S1 nuclease protection analysis suggested that the 5' untranslated region (UTR) of VSP1267 mRNA consists of a single nucleotide (nt). Primer extension sequencing mapped the site of VSP1267 transcript polyadenlyation 25 nt beyond the termination codon. vsp1267 contained no introns and predicted a cysteine-rich polypeptide with features common to other VSPs. Comparison of vsp1267 with another VSP gene sequence revealed striking conservation, both at the nucleotide and amino acid levels, at the 3' ends of the genes. An oligonucleotide derived from this region detected size-variant VSP transcripts in 4 of 5 G. lamblia clones analyzed, suggesting the general utility of this probe in studying VSP genes and their expression. RP MOWATT, MR (reprint author), NIAID,BLDG 4,LPD,ROOM 126,BETHESDA,MD 20892, USA. NR 37 TC 79 Z9 81 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 1991 VL 49 IS 2 BP 215 EP 228 DI 10.1016/0166-6851(91)90065-E PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA GQ438 UT WOS:A1991GQ43800004 PM 1775165 ER PT J AU CLARK, CG DIAMOND, LS AF CLARK, CG DIAMOND, LS TI RIBOSOMAL-RNA GENES OF PATHOGENIC AND NONPATHOGENIC ENTAMOEBA-HISTOLYTICA ARE DISTINCT SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE ENTAMOEBA-HISTOLYTICA; PATHOGENICITY; POLYMERASE CHAIN REACTION; RIBOPRINTING; RIBOSOMAL RNA GENE ID ISOENZYME PATTERNS; SURFACE-ANTIGEN; DNA; DIFFERENTIATION; STRAINS AB Most infections with Entamoeba histolytica are asymptomatic. Two forms of the organism can be distinguished biochemically, and this finding has been explained by two distinct hypotheses: (1) there are two morphologically indistinguishable species, one of which causes disease; (2) there is one species which exists in two interconvertible forms, one of which causes disease. Knowledge of which hypothesis is correct has major implications for evaluation and treatment of carriers. We have studied the ribosomal RNA genes of the two forms hypothesising that, if E. histolytica is one species, there should be no differences between them. We have found that the ribosomal RNA genes of the two forms are quite distinct, which supports the hypothesis that E. histolytica is two species. RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4-126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 19 TC 164 Z9 167 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 1991 VL 49 IS 2 BP 297 EP 302 DI 10.1016/0166-6851(91)90073-F PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA GQ438 UT WOS:A1991GQ43800012 PM 1685555 ER PT J AU DAAR, IO WHITE, GA SCHUH, SM FERRIS, DK WOUDE, GFV AF DAAR, IO WHITE, GA SCHUH, SM FERRIS, DK WOUDE, GFV TI TPR-MET ONCOGENE PRODUCT INDUCES MATURATION-PRODUCING FACTOR ACTIVATION IN XENOPUS OOCYTES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RIBOSOMAL-PROTEIN S6; CYCLIC-AMP PHOSPHODIESTERASE; GROWTH FACTOR-I; MEIOTIC MATURATION; AMPHIBIAN OOCYTES; ADENYLATE-CYCLASE; PROMOTING FACTOR; LAEVIS OOCYTES; CELL-CYCLE; REGULATORY SUBUNIT AB tpr-met, a tyrosine kinase oncogene, is the activated form of the met proto-oncogene that encodes the receptor for hepatocyte growth factor/scatter factor. The tpr-met product (p65tpr-met) was tested for its ability to induce meiotic maturation in Xenopus oocytes. While src and abl tyrosine kinase oncogene products have previously been shown to be inactive in this assay, p65tpr-met efficiently induced maturation-promoting factor (MPF) activation and germinal vesicle breakdown (GVBD) together with the associated increase in ribosomal S6 subunit phosphorylation. tpr-met-mediated MPF activation and GVBD was dependent on the endogenous c-mos(xe), while the increase in S6 protein phosphorylation was not significantly affected by the loss of mos function. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine inhibits tpr-met-mediated GVBD at concentrations that prevent insulin- but not progesterone-induced oocyte maturation. Moreover, maturation triggered by tpr-met is also inhibited by cyclic AMP-dependent protein kinase. This is the first demonstration that a tyrosine kinase oncogene product, p65tpr-met, can induce meiotic maturation in Xenopus oocytes and activate MPF through a mos-dependent pathway, possibly the insulin or insulinlike growth factor 1 pathway. C1 PRI DYN CORP INC,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. PRI DYN CORP INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. HOWARD HUGHES MED INST,DEPT BIOCHEM,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101] NR 61 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1991 VL 11 IS 12 BP 5985 EP 5991 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ932 UT WOS:A1991GQ93200022 PM 1719375 ER PT J AU WILLUMSEN, BM VASS, WC VELU, TJ PAPAGEORGE, AG SCHILLER, JT LOWY, DR AF WILLUMSEN, BM VASS, WC VELU, TJ PAPAGEORGE, AG SCHILLER, JT LOWY, DR TI THE BOVINE PAPILLOMAVIRUS-E5 ONCOGENE CAN COOPERATE WITH RAS - IDENTIFICATION OF P21-AMINO ACIDS CRITICAL FOR TRANSFORMATION BY C-RASH BUT NOT V-RASH SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE SARCOMA-VIRUS; SACCHAROMYCES-CEREVISIAE; ACTIVATING PROTEIN; VULVAR INDUCTION; CATALYTIC DOMAIN; GENE FAMILY; P21; HARVEY; GAP; ENCODES AB We have previously used a series of insertion-deletion mutants of the mutationally activated v-ras(H) gene to identify several regions of the encoded protein that are dispensable for cellular transformation (B. M. Willumsen, A. G. Papageorge, H.-F. Kung, E. Bekesi, T. Robins, M. Johnsen, W. C. Vass, and D. R. Lowy, Mol. Cell. Biol. 6:2646-2654, 1986). To determine if some of these amino acids are more important for the biological activity of c-ras(H), we have now tested many of the same insertion-deletion mutants in the c-ras(H) form for their ability to transform NIH 3T3 cells. Since the transforming activity of c-ras(H) is low, we have used cotransfection with the bovine papillomavirus (BPV) genome to develop a more sensitive transformation assay for c-ras(H) mutants. The increased sensitivity of the assay, which is seen both in focal transformation and in anchorage-independent growth, is mediated by cooperation between the BPV E5 gene and ras. E5-dependent cooperation was seen for v-ras(H) as well as for c-ras(H), which suggests that the major effect of E5 was to increase the susceptibility of the cell to transformation to a given level of ras activity. The cooperation assay was used to test the potential importance, in c-ras(H), of codons 93 to 108, 123 to 130, and 166 to 183, which were nonessential for v-ras(H) transformation. Relative to the respective transforming activity of wild-type c-ras(H) and v-ras(H), mutants with lesions in codons 102 and 103 were significantly less active in their c-ras(H) forms than in their v-ras(H) forms. We conclude that a region including amino acids 102 and 103 encodes a function that is more critical to c-ras(H) than to v-ras(H). Guanine nucleotide exchange is one function that is compatible with such a phenotype. C1 NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 1B-26,BETHESDA,MD 20892. UNIV COPENHAGEN,INST MICROBIOL,DK-1353 COPENHAGEN,DENMARK. RI Willumsen, Berthe/H-1903-2012 OI Willumsen, Berthe/0000-0002-2277-6999 NR 52 TC 55 Z9 55 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 DEC PY 1991 VL 11 IS 12 BP 6026 EP 6033 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ932 UT WOS:A1991GQ93200027 PM 1658623 ER PT J AU ALANI, R BROWN, P BINETRUY, B DOSAKA, H ROSENBERG, RK ANGEL, P KARIN, M BIRRER, MJ AF ALANI, R BROWN, P BINETRUY, B DOSAKA, H ROSENBERG, RK ANGEL, P KARIN, M BIRRER, MJ TI THE TRANSACTIVATING DOMAIN OF THE C-JUN PROTO-ONCOPROTEIN IS REQUIRED FOR COTRANSFORMATION OF RAT EMBRYO CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-1; V-JUN; TUMOR PROMOTERS; LEUCINE ZIPPERS; GENE-EXPRESSION; GROWTH-FACTORS; FOS; ONCOGENE; FIBROBLASTS; TRANSFORMATION AB The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20814. HOWARD HUGHES MED INST,LA JOLLA,CA 92037. UNIV CALIF SAN DIEGO,SCH MED,DEPT PHARMACOL,CTR HUMAN REPROD & REPROD BIOL,LA JOLLA,CA 92037. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RI Binetruy, Bernard/A-6465-2009; Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NCI NIH HHS [CA-50528] NR 54 TC 140 Z9 141 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1991 VL 11 IS 12 BP 6286 EP 6295 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ932 UT WOS:A1991GQ93200055 PM 1944289 ER PT J AU HERNANDEZ, ER HURWITZ, A BOTERO, L RICCIARELLI, E WERNER, H ROBERTS, CT LEROITH, D ADASHI, EY AF HERNANDEZ, ER HURWITZ, A BOTERO, L RICCIARELLI, E WERNER, H ROBERTS, CT LEROITH, D ADASHI, EY TI INSULIN-LIKE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION IN THE RAT OVARY - DIVERGENT REGULATION OF DISTINCT RECEPTOR SPECIES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; I IGF-I; THECA-INTERSTITIAL CELLS; ANDROGEN-PRODUCING CELLS; GRANULOSA-CELLS; SOMATOMEDIN-C; MECHANISM(S); BIOSYNTHESIS; BINDING; INVIVO AB The intraovarian insulin-like growth factor (IGF) system constitutes a triad composed of ligands, receptors, and binding proteins. Although conventional radioligand receptor assays have documented the presence of specific receptors for insulin and insulin-like peptides in some rat somatic ovarian cell types, the exact cellular localization and hormonal regulation of the receptors in question remain matters of inquiry. To reevaluate the very presence, cellular localization, and hormonal regulation of the IGF receptor gene family in the rat ovary, solution hybridization/RNase protection assays were used wherein ovarian total RNA (20-mu-g) from immature (21-23 days old) rats was hybridized with P-32-labled type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor riboprobes. Single protected fragments 261 (type IIGF receptor), 500 (type II IGF/mannose-6-posphate receptor), and 478 (insulin receptor) bases long were evident in whole ovary, granulosa, and theca-interstitial cells. Hypophysectomy of immature rats led to significant (P < 0.05) albeit variable decrements in the relative (densitometrically quantified) ovarian abundance of transcripts corresponding to the type I IGF (but not insulin or type II IGF/mannose-6-phosphate) receptor. Treatment of immature hypophysectomized rats with FSH (10-mu-g/rat.day x 2.5 days) resulted in a significant (P < 0.05) increase (4-fold) in transcripts corresponding to the type I IGF receptor in both whole ovarian material and freshly isolated granulosa cells. Similar (3.7-fold) increments (P < 0.05) were noted after treatment with a diethylstilbestrol-containing sc silastic implant applied for a total of 5 days. In contrast, treatment with either FSH or diethylstilbestrol was without effect on the relative abundance of whole ovarian transcripts corresponding to the type II IGF/mannose-6-phosphate or insulin receptor. Taken together, these findings document the ovarian granulosa and thecainterstitial cells as sites of type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor gene expression. Moreover, our present observations reveal a differential pattern of hormonal regulation wherein the ovarian type I IGF (but not the type II IGF/mannose-6-phosphate or insulin) receptor displays gonadotropin as well as estrogen dependence. As such, these observations document the ovarian expression of all members of the IGF receptor family while highlighting the exclusive hormonal responsiveness of type I IGF receptors, whose dynamic involvement in the ovarian life cycle has been previously proposed. C1 NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. RP HERNANDEZ, ER (reprint author), UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL,BRESSLER RES BLDG,BALTIMORE,MD 21201, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NICHD NIH HHS [HD-19998, HD-00697] NR 29 TC 33 Z9 33 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1991 VL 5 IS 12 BP 1799 EP 1805 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH372 UT WOS:A1991HH37200004 PM 1724286 ER PT J AU SAEKI, T CRISTIANO, A LYNCH, MJ BRATTAIN, M KIM, N NORMANNO, N KENNEY, N CIARDIELLO, F SALOMON, DS AF SAEKI, T CRISTIANO, A LYNCH, MJ BRATTAIN, M KIM, N NORMANNO, N KENNEY, N CIARDIELLO, F SALOMON, DS TI REGULATION BY ESTROGEN THROUGH THE 5'-FLANKING REGION OF THE TRANSFORMING GROWTH-FACTOR ALPHA GENE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN-BREAST CANCER; MESSENGER RIBONUCLEIC-ACID; MAMMARY EPITHELIAL-CELLS; 5' FLANKING REGION; TGF-ALPHA; TRANSGENIC MICE; FACTOR RECEPTOR; REPORTER GENE; EGF-RECEPTOR; FIREFLY LUCIFERASE AB Expression of transforming growth factor-alpha (TGF-alpha) mRNA and protein can be stimulated by estrogens such as 17-beta-estradiol (E2) in estrogen-responsive rodent and human breast cancer cells. To ascertain if E2 can directly regulate TGF-alpha expression through the 5'-flanking region of the human TGF-alpha gene, E2-responsive MCF-7 or ZR-75-1 human breast cancer cells or E2-nonresponsive MDA-MB-231 breast cancer cells were transiently transfected with a plasmid containing an 1140-base pair (bp) Sac-I fragment of the TGF-alpha 5'-flanking region ligated to the chloramphenicol acetyltransferase (CAT) gene. Cells that were transfected and subsequently treated with physiological concentrations of E2 (10(-11)-10(-8) M) for 24 h exhibited a 2- to 10-fold increase in CAT activity. The E2 stimulation of CAT activity was dose-dependent with an increase first found at 10(-10) M E2. The increase in CAT activity could be detected within 24-36 h after the addition of E2. There was no significant change in CAT activity in transiently transfected MDA-MB-231 cells as mediated through the TGF-alpha 5'-flanking region after E2 treatment. MCF-7 cells were also transiently transfected with different fragments of the TGF-alpha 5'-flanking region ligated to the luciferase gene. In the absence of E2 treatment, no detectable luciferase activity was found. E2 was able to stimulate, in a dose-dependent manner, a 30- to 300-fold increase in luciferase activity in MCF-7 cells, which have been transfected with either a 2813-bp Pst-I, a 1565-bp Spe-I, a 1140-bp Sac-I, or a 370-bp Bam-HI TGF-alpha-luciferase fragment. However, a loss in E2 responsiveness occurred when MCF-7 cells were transfected with a 77-bp Sac-II TGF-alpha-luciferase plasmid. The induction of luciferase activity by E2 could be effectively blocked by simultaneous treatment of the cells with the antiestrogens tamoxifen or droloxifene. In addition, the increase in luciferase activity was specific for E2 since progesterone or dexamethasone were ineffective in modifying luciferase activity through the TGF-alpha 5'-flanking sequence. The results show that the TGF-alpha 5'-flanking region contains a potential estrogen-responsive element(s) and that this region is upstream of the Sac-II restriction site. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B39,BETHESDA,MD 20892. NCI,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB CO,DEPT CELLULAR & MOLEC BIOL,BRISTOL MYERS PHARMACEUT RES & DEV DIV,WALLINGFORD,CT 06492. NR 52 TC 81 Z9 81 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1991 VL 5 IS 12 BP 1955 EP 1963 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH372 UT WOS:A1991HH37200022 PM 1791840 ER PT J AU RIEGEL, AT LU, Y REMENICK, J WOLFORD, RG BERARD, DS HAGER, GL AF RIEGEL, AT LU, Y REMENICK, J WOLFORD, RG BERARD, DS HAGER, GL TI PROOPIOMELANOCORTIN GENE PROMOTER ELEMENTS REQUIRED FOR CONSTITUTIVE AND GLUCOCORTICOID-REPRESSED TRANSCRIPTION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PRO-OPIOMELANOCORTIN GENE; NEGATIVE REGULATION; DNA-BINDING; NUCLEAR EXTRACTS; TATA BOX; C-JUN; EXPRESSION; RECEPTOR; HORMONE; INVIVO AB The POMC gene is expressed predominantly in the anterior pituitary. The high level of POMC transcription in this tissue is modulated by peptide hormones and repressed by glucocorticoids. In this present study we have investigated promoter elements required for the high basal transcription and glucocorticoid repression using transient transfection and in vitro transcription assays. We first determined that the region between -77 to -51 of the promoter, which has previously been shown to harbor a glucocorticoid receptor-binding site, is required for high basal expression both in vivo and in vitro. This promoter domain is also required for glucocorticoid repression of transcription in vivo. Two site-directed mutants within this area both decreased basal transcription, but were fully repressed by glucocorticoids, implying that the -77 to -51 region is a complex regulatory region harboring separable basal and glucocorticoid-repressible elements. Electrophoretic mobility shift and exonuclease III footprinting analysis revealed the existence of two factors that bind in this region. We also examined the effect of broad promoter deletions on basal expression and glucocorticoid repression. These experiments revealed that the region between -480 and -320 is also required for glucocorticoid repression. Taken together, the data suggest a model in which high basal transcription is generated by direct interaction of factors binding between -480 to -320 and -77 to -51. Glucocorticoid repression could occur by direct receptor disruption of these interactions. C1 NCI,HORMONE ACT & ONCOGENESIS SECT,MOLEC VIROL LAB,BETHESDA,MD 20892. RP RIEGEL, AT (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007, USA. FU NIDDK NIH HHS [DK-43127-01] NR 28 TC 39 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1991 VL 5 IS 12 BP 1973 EP 1982 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH372 UT WOS:A1991HH37200024 PM 1791842 ER PT J AU KAMEYAMA, L FERNANDEZ, L COURT, DL GUARNEROS, G AF KAMEYAMA, L FERNANDEZ, L COURT, DL GUARNEROS, G TI RNASEIII ACTIVATION OF BACTERIOPHAGE-LAMBDA N SYNTHESIS SO MOLECULAR MICROBIOLOGY LA English DT Article ID INT GENE-EXPRESSION; ESCHERICHIA-COLI; PHAGE-LAMBDA; COLIPHAGE-LAMBDA; ANTI-TERMINATION; TRANSCRIPTION ANTITERMINATION; RECOGNITION SITE; CLONING VEHICLES; MESSENGER-RNA; DNA-SEQUENCE AB The bacteriophage lambda-N gene product is one of the first genes expressed during phage development. N protein allows the expression of other phage genes by altering the transcription elongation process so as to prevent transcription termination. We have found that N levels may be modulated soon after induction or infection. Using N-lacZ fusions, we determined that cells containing RNaseIII have at least a fourfold greater expression than cells defective for RNaseIII. This effect is exerted at the post-transcriptional level. RNaseIII processes an RNA stem structure in the N-leader RNA. Removal of the stem structure by deletion increases N expression and prevents further stimulation by RNaseIII. The base of this stable stem is adjacent to the N ribosome binding site. We present a model for control of N synthesis in which this stable stem inhibits ribosome access to the N mRNA. C1 NCI,FREDERICK CANC RES DEV CTR,ABL BASIC RES PROGRAM,MOLEC CONTROL & GENET SECT,FREDERICK,MD 21702. INST POLITECN NACL,CTR INVEST ESTUDIOS AVANZADOS,DEPT GENET & BIOL MOLEC,MEXICO CITY 07000,DF,MEXICO. FU NCI NIH HHS [N01-CO-74101] NR 45 TC 42 Z9 42 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 1991 VL 5 IS 12 BP 2953 EP 2963 DI 10.1111/j.1365-2958.1991.tb01855.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GW806 UT WOS:A1991GW80600012 PM 1839745 ER PT J AU BROOKS, GF OLINGER, L LAMMEL, CJ BHAT, KS CALVELLO, CA PALMER, ML KNAPP, JS STEPHENS, RS AF BROOKS, GF OLINGER, L LAMMEL, CJ BHAT, KS CALVELLO, CA PALMER, ML KNAPP, JS STEPHENS, RS TI PREVALENCE OF GENE-SEQUENCES CODING FOR HYPERVARIABLE REGIONS OF OPA (PROTEIN-II) IN NEISSERIA-GONORRHOEAE SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEINS; MONOCLONAL-ANTIBODIES; GONOCOCCUS INFECTION; ANTIGENIC VARIATION; SURFACE-PROTEINS; PHASE VARIATION; LEUKOCYTE ASSOCIATION; HUMAN-NEUTROPHILS; ESCHERICHIA-COLI; COLONY OPACITY AB Opas (protein IIs) are a family of surface-exposed proteins of Neisseria gonorrhoeae. Each strain of N. gonorrhoeae has multiple (10-11) genes encoding for Opas. Identifiable elements in opa genes include the coding repeat within the signal sequence, conserved 5' and 3' regions, and hypervariable regions (HV1 and HV2) located within the structural gene. N. gonorrhoeae strains appear to have many biological properties in common that are either HV-region-mediated or associated with the presence of specific HV regions, suggesting that HV regions could be found in many clinical isolates. Oligonucleotides from three source strains representing three conserved regions of opa, 12 HV1 regions, and 14 HV2 regions were used by dot blot analysis to probe 120 clinical isolates of N. gonorrhoeae. The probe for the coding repeat hybridized to all 120 strains, the 3' conserved-region probe reacted with 98% of the strains, and the 5' conserved-region probe with 90% of the strains. Nine HV1 probes hybridized to 3.3-39.2% of the strains, and 13 of the HV2 probes hybridized to 1.7-25% of the isolates. Analysis of the number of probes that hybridized to each of the isolates showed that 19% did not hybridize with any of the HV1 probes and 25% did not hybridize with any of the HV2 probes. Approximately three-quarters of the isolates hybridized with one, two or three of the HV1 probes or one, two or three of the HV2 probes; 89% of the isolates hybridized to least one HV1 or one HV2 probe. The data indicate that some genes encoding HV regions of N. gonorrhoeae Opa proteins are widely distributed in nature. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. CTR DIS CONTROL,DIV SEXUALLY TRANSMITTED DIS LAB RES,ATLANTA,GA 30333. RP BROOKS, GF (reprint author), UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143, USA. FU NIAID NIH HHS [2 PO1 AI21912] NR 48 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 1991 VL 5 IS 12 BP 3063 EP 3072 DI 10.1111/j.1365-2958.1991.tb01866.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GW806 UT WOS:A1991GW80600023 PM 1809845 ER PT J AU ZHU, SY CUNNINGHAM, ML GRAY, TE NETTESHEIM, P AF ZHU, SY CUNNINGHAM, ML GRAY, TE NETTESHEIM, P TI CYTOTOXICITY, GENOTOXICITY AND TRANSFORMING ACTIVITY OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) IN RAT TRACHEAL EPITHELIAL-CELLS SO MUTATION RESEARCH LA English DT Article DE NNK; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; TOBACCO-SPECIFIC NITROSAMINE; RTE CELL TRANSFORMATION; MICRONUCLEUS; SALMONELLA MUTAGENESIS ID TOBACCO-SPECIFIC NITROSAMINES; SYRIAN GOLDEN-HAMSTER; SERUM-FREE MEDIUM; CHEMICAL CARCINOGENESIS; N-NITROSAMINES; CLONAL PROLIFERATION; GROWTH-FACTORS; FETAL TISSUES; DOSE-RESPONSE; LUNG-CANCER AB The cytotoxicity, genotoxicity and transforming activity of 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanone (NNK) were studied by the assays of colony-forming efficiency (CFE), micronucleus formation (MN), and cell transformation in rat tracheal epithelial (RTE) cells both in vitro and in vivo. Liver S9, primary hepatocytes and RTE cells from normal and Aroclor-1254 induced rats were compared for bioactivation of NNK using Salmonella mutagenesis as the endpoint. Results from the in vitro experiments indicated that low concentrations of NNK (0.01-25-mu-g/ml) caused from 15% to > 100% increases in CFE of RTE cells. At high concentrations (100-200-mu-g/ml), NNK was significantly toxic to RTE cells. NNK treatment in vitro (50-200-mu-g/ml) increased MN frequency as much as 3-fold above background and significantly increased the transformation frequency (TF) in 4/5 (50-mu-g/ml) and 6/8 (100-mu-/ml) experiments. The in vivo exposure of rats to NNK (150-450 mg/kg, given i.p.) resulted in a 60-85% reduction in CFE and a 3-5-fold increase in MN formation in RTE cells. In vivo treatment with cumulative doses of 150 and 300 mg/kg of NNK produced significant increases in TF of tracheal cells from 3/3 and 2/3 rats, respectively. Without activation, NNK was not mutagenic in Salmonella TA1535. The bioactivation of NNK to a mutagenic metabolite was achieved by incubation of NNK with liver S9 fraction from Aroclor-1254 induced rats or primary hepatocytes from both untreated and Aroclor-1254 pretreated rats. RTE cells did not produce sufficient quantities of mutagenic NNK metabolites to be detected by the Salmonella assay. The results of our studies indicate that NNK, one of the major carcinogens in tobacco smoke, is able to cause transformation of tracheo-bronchial epithelium. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. NR 37 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD DEC PY 1991 VL 261 IS 4 BP 249 EP 259 DI 10.1016/0165-1218(91)90040-S PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GT282 UT WOS:A1991GT28200002 PM 1722280 ER PT J AU DRAKE, JW AF DRAKE, JW TI FREESE,ERNST (1925-1990) - OBITUARY SO MUTATION RESEARCH LA English DT Item About an Individual RP DRAKE, JW (reprint author), NIEHS,MOLEC GENET LAB E301,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD DEC PY 1991 VL 251 IS 2 BP 165 EP 169 DI 10.1016/0027-5107(91)90071-U PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GT810 UT WOS:A1991GT81000001 PM 1720866 ER PT J AU LEUNG, E JACOBSON, KA GREEN, RD AF LEUNG, E JACOBSON, KA GREEN, RD TI APPARENT HETEROGENEITY OF CARDIAC A1 ADENOSINE RECEPTORS AS REVEALED BY RADIOLIGAND BINDING EXPERIMENTS ON N-ETHYLMALEIMIDE-TREATED MEMBRANES SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE A1 ADENOSINE RECEPTOR; N-ETHYLMALEIMIDE PRETREATMENT; RECEPTOR SUBTYPES ID ANTAGONIST RADIOLIGAND; ADENYLATE-CYCLASE; LIGAND-BINDING; A1-ADENOSINE RECEPTORS; BRAIN MEMBRANES; HIGH-AFFINITY; AGONIST; 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE; PHOSPHORYLATION; HEART AB While G protein-coupled receptors are often studied by analyzing antagonist radioligand: "cold" agonist inhibition curves using an independent site model, it is now clear that K(L) and K(H) values determined in these analyses are not reliable estimates of the affinities of the agonists for "free" and G protein-coupled forms of the receptor. Thus, such experiments cannot be used to contrast the characteristics of a given type of receptor in different tissues, i.e., to probe for the existence of receptor subtypes. Since treatment with N-ethylmaleimide treatment blocks receptor: G(i)/G(o) protein interactions, such analyses on N-ethylmaleimide-pretreated membranes should allow direct assessment of the affinities of competing ligands for the free receptor or for multiple receptor subtypes. As A1 adenosine receptors couple to G(i), and perhaps to G(o), we have performed A1 adenosine receptor radioligand "competition" studies first on control, then on N-ethylmaleimide-pretreated bovine cardiac and cerebral cortical membranes. Results of experiments with the antagonist radioligand [H-3]xanthine amine congener appeared to be confounded by ligand binding to A2 adenosine receptors present in the cardiac membrane preparations. Further experiments utilized the A1-specific radioligand [H-3]1,3-dipropyl-8-cyclopentylxanthine. These experiments confirmed once more that the K(L) values determined by computer analysis of "competition" curves performed on control membranes are not reliable estimates of the affinities of the competing ligand for free receptors. Furthermore the results supported the hypothesis that similar analyses on NEM-treated membranes provide reliable estimates of the affinity(s) of competing ligands for free receptors. Lastly, the results suggest that cardiac membranes contain two subtypes of A1 adenosine receptors that are differentiated by 5'-modified but not N6-modified adenosine analogs. One of these receptor subtypes appears to be the same as the A1 receptor detected in cortical membranes. C1 UNIV ILLINOIS,COLL MED,DEPT PHARMACOL,CHICAGO,IL 60680. NIDDKD,CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 25 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD DEC PY 1991 VL 344 IS 6 BP 639 EP 644 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW539 UT WOS:A1991GW53900004 PM 1775196 ER PT J AU VYKLICKY, L PATNEAU, DK MAYER, ML AF VYKLICKY, L PATNEAU, DK MAYER, ML TI MODULATION OF EXCITATORY SYNAPTIC TRANSMISSION BY DRUGS THAT REDUCE DESENSITIZATION AT AMPA KAINATE RECEPTORS SO NEURON LA English DT Article ID AMINO-ACID RECEPTORS; CULTURED HIPPOCAMPAL-NEURONS; QUISQUALATE RECEPTORS; SINGLE-CHANNEL; GLUTAMATE RECEPTORS; CONCANAVALIN-A; CURRENTS; ACTIVATION; VOLTAGE; ACETYLCHOLINE AB Desensitization at AMPA/kainate receptors has been proposed to contribute to the decay of excitatory synaptic currents. We examined the action of aniracetam, wheat germ agglutinin (WGA), and concanavalin A (Con A), drugs that act via separate mechanisms to reduce desensitization evoked by L-glutamate in rat hippocampal neurons. The decay of excitatory synaptic currents, and sucrose-evoked miniature excitatory postsynaptic currents (EPSCs) was slowed 2- to 3-fold by aniracetam. In contrast, WGA increased the EPSC decay time constant only 1.3-fold and Con A had no effect. Aniracetam increased the magnitude of stimulus-evoked EPSCs 1.9-fold; variance analysis suggests a postsynaptic mechanism of action. WGA and Con A reduced EPSC amplitude via a presynaptic mechanism. Aniracetam increased the burst length of L-glutamate-activated single-channel responses. Simulations suggest that aniracetam either slows entry into a desensitized state or decreases the closing rate constant for ion channel gating. C1 CZECHOSLOVAK ACAD SCI,INST PHYSIOL,CS-11142 PRAGUE 1,CZECHOSLOVAKIA. RP VYKLICKY, L (reprint author), NICHHD,NEUROPHYSIOL & BIOPHYS SECT,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. RI Vyklicky, Ladislav/C-1851-2012; Mayer, Mark/H-5500-2013 OI Vyklicky, Ladislav/0000-0002-0015-0098; NR 37 TC 213 Z9 213 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 1991 VL 7 IS 6 BP 971 EP 984 DI 10.1016/0896-6273(91)90342-W PG 14 WC Neurosciences SC Neurosciences & Neurology GA GY438 UT WOS:A1991GY43800010 PM 1684903 ER PT J AU LISTER, RG LINNOILA, M AF LISTER, RG LINNOILA, M TI ALCOHOL, THE CHLORIDE IONOPHORE AND ENDOGENOUS LIGANDS FOR BENZODIAZEPINE RECEPTORS SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT SYMP ON DIAZEPAM BINDING INHIBITOR : A NOVEL PEPTIDE WITH MULTIPLE FUNCTIONS CY NOV 29-30, 1990 CL GEORGETOWN UNIV, WASHINGTON, DC SP FIDIA RES FDN HO GEORGETOWN UNIV DE ALCOHOL; BENZODIAZEPINES; DIAZEPAM BINDING INHIBITOR; GABA; CHLORIDE CHANNEL ID GAMMA-AMINOBUTYRIC ACID; ANTAGONIST RO 15-1788; DIAZEPAM-BINDING INHIBITOR; ETHANOL WITHDRAWAL; GABAERGIC TRANSMISSION; RAT; INTOXICATION; RO-15-1788; RO15-4513; CHANNELS AB Considerable evidence suggests that at least some of the effects of ethanol are mediated by an action on the GABA(A) receptor chloride channel complex. More speculative is the suggestion that ethanol might interact with endogenous ligands for the benzodiazepine receptor on the complex. This paper considers the evidence for such interactions. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BLDG 10,ROOM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 50 TC 20 Z9 20 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1991 VL 30 IS 12B BP 1435 EP 1440 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA GY727 UT WOS:A1991GY72700013 PM 1723509 ER PT J AU VINAR, O KLEIN, DF POTTER, WZ GAUSE, EM AF VINAR, O KLEIN, DF POTTER, WZ GAUSE, EM TI A SURVEY OF PSYCHOTROPIC MEDICATIONS NOT AVAILABLE IN THE UNITED-STATES SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material DE NEUROPHARMACOLOGY; PSYCHOPHARMACOLOGY; DRUG INDUSTRY; LEGISLATION, DRUG; DRUG THERAPY; DRUG EVALUATION ID DOUBLE-BLIND TRIAL; UNDERLYING AUTORECEPTOR SELECTIVITY; DOPAMINE-RECEPTOR AGONISTS; CLINICAL-TRIAL; SCHIZOPHRENIC-PATIENTS; DRUG INTRODUCTIONS; NICOTIANA-GLAUCA; METABOLIC-FATE; PSYCHOSTIMULANT SYDNOCARB; UNDERSTANDING COMPARISONS AB The range of psychotropic medications available in the U.S. for the treatment of serious mental illnesses is limited. Many agents have been "me too" drugs, offering primarily side-effect differences, instead of new indications or mechanisms. As a result, patients refractory to the original drugs are not helped. Other patient populations (both mentally ill and addicted) have "fallen through the cracks" of the current U.S. psychotropic drug development process. The recent approval of chlorimipramine and clozapine demonstrates that real benefits for U.S. patients can be realized from judicious introduction of non-U.S. drugs. Many more psychotropic drugs developed and used in other countries are not available in the United States. Industrial and regulatory obstacles could be surmounted by the legislative innovation proposed. This survey identifies some specific non-U.S. drugs of interest. C1 ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,5600 FISHERS LANE,ROCKVILLE,MD 20857. STATE INST DRUG CONTROL,PRAGUE,CZECHOSLOVAKIA. CZECHOSLOVAK ACAD SCI,INST ORGAN CHEM & BIOCHEM,JOINT LAB,CS-11142 PRAGUE 1,CZECHOSLOVAKIA. NIMH,CLIN PHARMACOL SECT,DIRP,BETHESDA,MD 20892. NR 111 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1991 VL 5 IS 4 BP 201 EP 217 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA GX697 UT WOS:A1991GX69700001 PM 1804161 ER PT J AU WEBSTER, MJ UNGERLEIDER, LG BACHEVALIER, J AF WEBSTER, MJ UNGERLEIDER, LG BACHEVALIER, J TI LESIONS OF INFERIOR TEMPORAL AREA TE IN INFANT MONKEYS ALTER CORTICO-AMYGDALAR PROJECTIONS SO NEUROREPORT LA English DT Article DE DEVELOPMENT; PLASTICITY; MEMORY; LIMBIC SYSTEM; NONHUMAN PRIMATE ID CONNECTIONS; SYSTEM; PLASTICITY; AXONS; RATS AB WHEN inferior temporal area TE is removed bilaterally in infant monkeys, the normally transient projection from area TEO to the lateral basal nucleus of the amygdala is maintained, and the normally limited projection from area TEO to the dorsal part of the lateral nucleus of the amygdala expands to invade the terminal space in the lateral nucleus that is normally occupied by terminals from area TE. The maintenance and sprouting of these projections from area TEO could play a role in the permanent preservation of visual memory ability in monkeys that have received bilateral removal of area TE in infancy. C1 NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1N107,BETHESDA,MD 20892. NR 25 TC 38 Z9 38 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 DEC PY 1991 VL 2 IS 12 BP 769 EP 772 DI 10.1097/00001756-199112000-00010 PG 4 WC Neurosciences SC Neurosciences & Neurology GA GX279 UT WOS:A1991GX27900010 PM 1724388 ER PT J AU CREPEAU, LJ NEWMAN, JD AF CREPEAU, LJ NEWMAN, JD TI GENDER DIFFERENCES IN REACTIVITY OF ADULT SQUIRREL-MONKEYS TO SHORT-TERM ENVIRONMENTAL CHALLENGES SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT ETHOPHARMACOLOGY CONF : ADVANCES IN ETHOPHARMACOLOGY CY APR 02-06, 1991 CL LISEK, CZECHOSLOVAKIA SP DUPHAR DE GENDER DIFFERENCES; DEFENSIVE BEHAVIOR; PRIMATE MODELS; PANIC; ANXIETY; VOCALIZATION; BENACTYZINE ID SAIMIRI-OERSTEDI; CALL AB Evidence is presented to show that individual adult squirrel monkeys show gender-specific reactivity profiles to threatening stimuli under laboratory conditions, and that a putative anxiogenic drug, benactyzine hydrochloride, enhances the vocal response to threatening stimuli, but otherwise preserves the relative importance of the stimuli to both males and females. These data support the conclusion that screening of putative anxiolytic drugs in a primate model can be accomplished using efficient, ethologically based testing procedures in the laboratory. C1 NICHHD,CTR ANIM,COMPARAT ETHOL LAB,BOX 289,BLDG 112,POOLESVILLE,MD 20837. RP NEWMAN, JD (reprint author), NICHHD,CTR ANIM,COMPARAT ETHOL LAB,BOX 289,BLDG 112,POOLESVILLE,MD 20837, USA. NR 13 TC 14 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD WIN PY 1991 VL 15 IS 4 BP 469 EP 471 DI 10.1016/S0149-7634(05)80133-2 PG 3 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA GV085 UT WOS:A1991GV08500006 PM 1686486 ER PT J AU ROBINSON, GW WRAY, S MAHON, KA AF ROBINSON, GW WRAY, S MAHON, KA TI SPATIALLY RESTRICTED EXPRESSION OF A MEMBER OF A NEW FAMILY OF MURINE DISTAL-LESS HOMEOBOX GENES IN THE DEVELOPING FOREBRAIN SO NEW BIOLOGIST LA English DT Article DE DEVELOPMENT; DISTAL-LESS; FOREBRAIN; GENE FAMILIES; HOMEOBOX; HYPOTHALAMUS; PROSENCEPHALON ID LIMB DEVELOPMENT; SEGMENTATION GENES; PATTERN-FORMATION; MOUSE DEVELOPMENT; FLOOR PLATE; DROSOPHILA; BOX; ORGANIZATION; HOMEODOMAIN; COMPLEXES C1 NICHHD, MAMMALIAN GENES & DEV LAB, BETHESDA, MD 20892 USA. NINCDS, NEUROCHEM LAB, BETHESDA, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 NR 46 TC 128 Z9 131 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD DEC PY 1991 VL 3 IS 12 BP 1183 EP 1194 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GX869 UT WOS:A1991GX86900008 PM 1687503 ER PT J AU VERVOORT, J RIETJENS, IMCM MOONEN, CTW VONKIENLIN, M DESPRES, D AF VERVOORT, J RIETJENS, IMCM MOONEN, CTW VONKIENLIN, M DESPRES, D TI BIOTRANSFORMATION OF 2-FLUOROANILINE IN RATS STUDIED BY INVIVO F-19 NMR SO NMR IN BIOMEDICINE LA English DT Article ID METABOLISM AB The present study describes results from an in vivo F-19 NMR study on rats exposed to the xenobiotic compound 2-fluoroaniline. Qualitative pharmacokinetics and the biotransformation of 2-fluoroaniline were studied after exposure to 50 m/kg body wt 2-fluoroaniline. Accumulation and elimination of the parent compound in and from the liver of exposed animals were readily observed. Metabolites formed in the liver were shown to be efficiently excreted from the liver, as the amount of metabolites in this organ was always < 10% of the maximum amount of the parent compound observed. In the bladder, rapid accumulation of 2-fluoroaniline-derived metabolites was detected. The metabolite pattern was shown to change in time, with the parent compound being dominantly present during the first hours of exposure. N-acetylated products (4-acetamido-3-fluorophenyl sulphate and 4-acetamido-3-fluorophenyl glucuronide) were observed to accumulate more slowly in the bladder than the non-acetylated products (4-amino-3-fluorophenyl sulphate and 4-amino-3-fluorophenyl glucuronide). Urine metabolite patterns obtained from the bladder in vivo were compared to those obtained during metabolic cage experiments. C1 NIH,INVIVO NMR RES CTR,BETHESDA,MD 20892. RP VERVOORT, J (reprint author), AGR UNIV WAGENINGEN,DEPT BIOCHEM,DREIJENLAAN 3,6703 HA WAGENINGEN,NETHERLANDS. RI Moonen, Chrit/K-4434-2016; OI Moonen, Chrit/0000-0001-5593-3121; Rietjens, Ivonne/0000-0003-1894-3544; von Kienlin, Markus/0000-0002-7972-3003 NR 10 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 1991 VL 4 IS 6 BP 255 EP 261 DI 10.1002/nbm.1940040602 PG 7 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA GW131 UT WOS:A1991GW13100001 PM 1816804 ER PT J AU COTCH, MF PASTOREK, JG NUGENT, RP YERG, DE MARTIN, DH ESCHENBACH, DA AF COTCH, MF PASTOREK, JG NUGENT, RP YERG, DE MARTIN, DH ESCHENBACH, DA TI DEMOGRAPHIC AND BEHAVIORAL PREDICTORS OF TRICHOMONAS-VAGINALIS INFECTION AMONG PREGNANT-WOMEN SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOWER GENITAL-TRACT; LABORATORY DIAGNOSIS; PREVALENCE; CANDIDIASIS; DISEASE; FLORA AB There is little available information on the demographic and behavioral factors associated with Trichomonas vaginalis in pregnant women. Among 13,816 women from six urban clinic centers, the prevalence rate by culture at mid-pregnancy was 12.6%. Women colonized with T vaginalis were significantly more likely to be black, cigarette smokers, unmarried, and less educated (all P < .01). Several behavioral factors associated with T vaginalis included greater numbers of sexual partners both lifetime and in the last year, 5 years or more of sexual activity, and a history of gonorrhea (all P < .01). Trichomonas vaginalis-colonized women were less sexually active in the preceding month compared with uncolonized women (P < .01). Women using either barrier or oral contraception in the 6 months before becoming pregnant were far less likely to be colonized (P < .01). Other factors such as age, gravidity, income level, age at first coitus, and use of antibiotics, alcohol, or douche during pregnancy were not independently associated with T vaginalis colonization. Because many of the factors predictive of increased risk of colonization have also been shown to be associated with adverse pregnancy outcome, they should be considered in assessing the association of T vaginalis with adverse pregnancy outcome. C1 NICHHD,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. UNIV WASHINGTON,SEATTLE,WA 98195. RP COTCH, MF (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,CONTROL DATA BLDG,ROOM 3A24,BETHESDA,MD 20892, USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999]; NICHD NIH HHS [HD-3-2832, HD-3-2833, HD-3-2834] NR 29 TC 79 Z9 81 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1991 VL 78 IS 6 BP 1087 EP 1092 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA GR679 UT WOS:A1991GR67900020 PM 1945213 ER PT J AU FISHER, RJ MAVROTHALASSITIS, G KONDOH, A PAPAS, TS AF FISHER, RJ MAVROTHALASSITIS, G KONDOH, A PAPAS, TS TI HIGH-AFFINITY DNA PROTEIN INTERACTIONS OF THE CELLULAR ETS1 PROTEIN - THE DETERMINATION OF THE ETS BINDING MOTIF SO ONCOGENE LA English DT Article ID LONG TERMINAL REPEAT; GEL-ELECTROPHORESIS; SEQUENCE; PHOSPHORYLATION; OPERATOR; COMPLEX; DOMAIN; VIRUS; GENE AB ETS1 protein purified from CEM cells was used to select its optimum DNA-binding sequence (pu) G/CC(a)GGA-AGT(c) (py). The sequence CCGGAAGT (ETS1-3) was preferred 5:1 over CAGGAAGT (PEA3). Quantitative electrophoretic mobility-shift assays (EMSA) indicated that the purified ETS1 protein binds to either ETS1-3 or PEA3 oligonucleotide probes with high affinity (K(a) = 0.5-4.0 x 10(10) M-1) and that the purified ETS1 has different binding capacities for ETFS1-3 and PEA3 oligonucleotide probes. The ETS1 protein binds 2-5 times more ETS1-3 than PEA3. Competitive binding experiments showed that the ETS1-3 and PEA3 probes effectively compete for the binding of ETS1-3. However, changing the core DNA-binding sequence from GGAA to AGAA eliminates competition. Since the human ETS1 protein selected the same DNA sequence from a mixture of random oligonucleotides as did the Drosophila E74A protein (one of the most divergent members of the ETS family), this strongly suggests that all proteins containing the ETS 85 amino acid domain (sequences which define the ETS family) will bind to the same sequence. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702. DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 NR 23 TC 91 Z9 91 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1991 VL 6 IS 12 BP 2249 EP 2254 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX735 UT WOS:A1991GX73500011 PM 1766672 ER PT J AU KIM, RY SAPERSTEIN, DA NICKERSON, JM AF KIM, RY SAPERSTEIN, DA NICKERSON, JM TI INDEPENDENT SEGREGATION OF FUNDUS-ALBIPUNCTATUS AND THE TRANSTHYRETIN (PREALBUMIN) GENE SO OPHTHALMIC PAEDIATRICS AND GENETICS LA English DT Article DE FUNDUS-ALBIPUNCTATUS; TRANSTHYRETIN; PREALBUMIN; POLYMORPHISM; RFLP; RECOMBINANT DNA AB A defect in the visual cycle has been suspected in patients with fundus albipunctatus (FALB), rendering genes encoding visual cycle components etiologic candidates. One such component is the retinoid and thyroxine transport protein transthyretin (TTR, prealbumin) which in the eye is synthesized only in the retinal pigment epithelium and is believed to play a role in retinal retinoid transport. The authors established polymerase chain reaction conditions that allow rapid assay of TTR alleles as defined by MspI and Fnu4HI restriction fragment length polymorphisms. In a candidate gene analysis of an affected family, they demonstrate independent segregation of the TTR and FALB disease loci. These results exclude the possibility that a TTR gene defect causes FALB in this family. RP KIM, RY (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,RM 204,BETHESDA,MD 20892, USA. FU NEI NIH HHS [F32 EY-06177] NR 0 TC 0 Z9 0 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0167-6784 J9 OPHTHALMIC PAED GEN PD DEC PY 1991 VL 12 IS 4 BP 171 EP 176 DI 10.3109/13816819109025813 PG 6 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA HB989 UT WOS:A1991HB98900003 PM 1687707 ER PT J AU YUSUF, S GARG, R ZUCKER, D AF YUSUF, S GARG, R ZUCKER, D TI ANALYSES BY THE INTENTION-TO-TREAT PRINCIPLE IN RANDOMIZED TRIALS AND DATABASES SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP YUSUF, S (reprint author), NHLBI,CLIN TRIAL BRANCH,FED BLDG ROOM 5C10,BETHESDA,MD 20784, USA. NR 4 TC 16 Z9 16 U1 2 U2 2 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 DEC PY 1991 VL 14 IS 12 BP 2078 EP 2082 DI 10.1111/j.1540-8159.1991.tb06476.x PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA GW113 UT WOS:A1991GW11300002 PM 1723188 ER PT J AU DUBNER, R AF DUBNER, R TI TOPICAL CAPSAICIN THERAPY FOR NEUROPATHIC PAIN SO PAIN LA English DT Editorial Material ID NEURALGIA RP DUBNER, R (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,BETHESDA,MD 20892, USA. NR 9 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 1991 VL 47 IS 3 BP 247 EP 248 DI 10.1016/0304-3959(91)90215-J PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA GW035 UT WOS:A1991GW03500001 PM 1664507 ER PT J AU VESIKARI, T RUUSKA, T KOIVU, HP GREEN, KY FLORES, J KAPIKIAN, AZ AF VESIKARI, T RUUSKA, T KOIVU, HP GREEN, KY FLORES, J KAPIKIAN, AZ TI EVALUATION OF THE M37 HUMAN ROTAVIRUS VACCINE IN 2-MONTH-OLD TO 6-MONTH-OLD INFANTS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE ROTAVIRUS; DIARRHEA; VACCINE ID VENEZUELAN INFANTS; YOUNG-CHILDREN; 4TH GENE; RHESUS; DIARRHEA; TRIAL; PROTECTION; RIT-4237; EFFICACY; REASSORTANT AB Human rotavirus strain M37, isolated from an asymptomatic neonate, was evaluated as a live oral vaccine in a double-blinded, placebo-controlled trial involving 282 infants ages 2 to 6 months. Either 10(4) or 10(5) plaque-forming units (PFU) of the M37 vaccine were tested in 102 and 39 infants, respectively. The vaccine was well-tolerated; fever on Days 1 to 7 after vaccination was recorded in 12 and 18% of infants receiving 10(4) and 10(5) PFU of the M37 vaccine, respectively, compared with 6% of those receiving placebo; none of the vaccinees developed diarrhea. A rotavirus IgA enzyme-linked immunosorbent assay serum antibody response was detected in 47 and 76% of the infants receiving the 10(4) and 10(5) PFU vaccines, respectively. No clinical protection against rotavirus diarrhea was observed in the group vaccinated with the 10(4) PFU dose; the number of infants vaccinated with 10(5) PFU was too small for evaluation of vaccine efficacy. The M37 vaccine in a titer of 10(4) PFU was found to be inadequate; the 10(5) PFU dose was more immunogenic than the lower dose and warrants further study for clinical efficacy. C1 TAMPERE UNIV HOSP,DEPT PEDIAT,TAMPERE,FINLAND. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP VESIKARI, T (reprint author), UNIV TAMPERE,DEPT BIOMED SCI,POB 607,SF-33101 TAMPERE,FINLAND. NR 36 TC 56 Z9 58 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 1991 VL 10 IS 12 BP 912 EP 917 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA GU156 UT WOS:A1991GU15600006 PM 1662796 ER PT J AU BRENNAN, MB AVDALOVIC, N AF BRENNAN, MB AVDALOVIC, N TI A STRATEGY FOR PHYSICAL MAPPING OF THE HUMAN GENOME SO PERIODICUM BIOLOGORUM LA English DT Article ID MAP AB We propose the physical mapping of the human genome from a large genomic library through the use of an ordered set of overlapping DNA clones that span the entire genome. The overlap relations among clones can be determined by repeated screening of the library with probes consisting of pooled cloned inserts. The minimum number of probings necessary for definition of a comprehensive set of overlapping clones can be determined by a simple algorithm. For this approach, most methods are standard in the technique of "chromosome walking." However, suitable instrumentation was required for the repeated and reproducible plating of highly dense large libraries needed in this approach. C1 DIONEX CHEM CORP,SUNNYVALE,CA 94088. RP BRENNAN, MB (reprint author), IRP,GEN UNIT,NIMH BLDG 10,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU PERIODICUM BIOLOGORUM PI ZAGREB PA HRVATSKO PRIRODOSLOVNO DRUSTVO ILICA 16/111, 41000 ZAGREB, CROATIA SN 0031-5362 J9 PERIOD BIOL PD DEC PY 1991 VL 93 IS 4 BP 583 EP 590 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA HK949 UT WOS:A1991HK94900013 ER PT J AU PETERSEN, DD KONG, ANT JORGE, LF NEBERT, DW ARIAS, TD AF PETERSEN, DD KONG, ANT JORGE, LF NEBERT, DW ARIAS, TD TI DEBRISOQUINE POLYMORPHISM - NOVEL CYP2D6 GENE BAM HI RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM IN THE NGAWBE-GUAYMI INDIAN OF PANAMA SO PHARMACOGENETICS LA English DT Article AB Markedly decreased cytochrome P450-mediated metabolism of debrisoquine, sparteine, and more than two dozen additional commonly prescribed drugs is an autosomal recessive trait that has been associated with several RFLP patterns involving the CYP2D6 gene. In Caucasians there are at least six variant alleles known to be correlated with the 'poor metabolizer' (PM) phenotype. We examined debrisoquine and sparteine metabolism and CYP2D6 RFLP patterns in 22 Ngawbe Guaymi Indians of Panama. We studied a two-generation family, a three-generation family, and three other unrelated PM individuals. Digestion of all 22 DNA samples with Xba I or Hind III did not produce the same varying CYP2D6 RFLP patterns as those commonly seen in at least two-thirds of all Northern European Caucasians and Chinese so far screened. In contrast, we found a single heretofore undescribed Bam HI polymorphism that was correlated with the PM phenotype among all Ngawbe Guaymi individuals examined. It is possible that this novel RFLP might represent a recent founder effect that has occurred in this unadmixed Amerindian tribe within the past 20 000-30 000 years. C1 NICHHD,DEV PHARMACOL LAB,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1991 VL 1 IS 3 BP 136 EP 142 DI 10.1097/00008571-199112000-00003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA LG850 UT WOS:A1991LG85000002 PM 1688244 ER PT J AU MURPHY, DL LESCH, KP AULAKH, CS PIGOTT, TA AF MURPHY, DL LESCH, KP AULAKH, CS PIGOTT, TA TI SEROTONIN-SELECTIVE ARYLPIPERAZINES WITH NEUROENDOCRINE, BEHAVIORAL, TEMPERATURE, AND CARDIOVASCULAR EFFECTS IN HUMANS .3. SO PHARMACOLOGICAL REVIEWS LA English DT Article; Proceedings Paper CT CONF ON SEROTONIN AND NEUROPSYCHIATRIC DISORDERS : IMPLICATIONS FOR THE DISCOVERY OF NEW PSYCHOTHERAPEUTIC AGENTS CY OCT 03, 1990 CL HERSHEY, PA SP HOECHST ROUSSEL PHARM ID OBSESSIVE-COMPULSIVE DISORDER; DISCRIMINATIVE STIMULUS PROPERTIES; DORSAL RAPHE NEURONS; PUTATIVE 5-HT1A AGONISTS; CENTRAL NERVOUS-SYSTEM; HYPERTONIC SALINE CONSUMPTION; ADENYLATE-CYCLASE ACTIVITY; ELEVATED PLUS-MAZE; 8-HYDROXY-2-(DI-N-PROPYLAMINO) TETRALIN 8-OH-DPAT; POTENTIAL ANXIOLYTIC PROPERTIES RP MURPHY, DL (reprint author), NIMH,CLIN SCI LAB,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 380 TC 157 Z9 157 U1 3 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 1991 VL 43 IS 4 BP 527 EP 552 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW852 UT WOS:A1991GW85200005 PM 1775507 ER PT J AU SPANGLER, EL BRESNAHAN, EL GAROFALO, P MUTH, NJ HELLER, B INGRAM, DK AF SPANGLER, EL BRESNAHAN, EL GAROFALO, P MUTH, NJ HELLER, B INGRAM, DK TI NMDA RECEPTOR CHANNEL ANTAGONISM BY DIZOCILPINE (MK-801) IMPAIRS PERFORMANCE OF RATS IN AVERSIVELY MOTIVATED COMPLEX MAZE TASKS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MK-801; GLUTAMATE RECEPTOR; CALCIUM CHANNELS; EXCITATORY AMINO ACIDS; AGING; LEARNING AND MEMORY ID LONG-TERM POTENTIATION; 14-UNIT T-MAZE; AMINO-ACID NEUROTRANSMISSION; METHYL-D-ASPARTATE; AGED RATS; MEMORY; ACQUISITION; DEFICITS; SCOPOLAMINE; MECHANISMS AB To determine the involvement of the N-methyl-D-aspartate (NMDA) receptor in shock-motivated complex maze performance, the drug dizocilpine (DIZO; a.k.a. MK-801) was administered a) to naive, 3-month-old male F-344 rats prior to acquisition (AQ) in the 14-unit T-maze (Experiment 1), and b) to well-trained 11-month-old male F-344 rats prior to testing in a delayed-matching-to-sample (DMTS) task in the detour maze (Experiment 2). For Experiment 1, rats first were pretrained in a straight runway one-way active avoidance (13/15 correct avoidance) for a maximum of 30 trials. On the following day, either DIZO 0.025 (n = 8), 0.05 (n = 8), 0.1 (n = 8), mg/kg, or saline (SAL; n = 15) was administered subcutaneously (SC) 20 min prior to 15 AQ trials in the shock-motivated 14-unit T-maze. The highest dose disrupted all measures of maze performance including errors, alternation errors, runtime, shock duration and frequency, but also produced marked motor ataxia. The 0.05-mg/kg group displayed significant impairment in AQ of this task but only on the cognitive measures, errors and alternation errors, and the 0.025-mg/kg group was impaired on the alternation measure only. One week later, the 15 SAL rats were divided into 2 groups and tested on retention with either SAL or 0.05 mg/kg DIZO. No effects on maze performance were observed. For Experiment 2, after receiving extensive pretraining in the shock-motivated detour maze, 7 rats were exposed to a novel sequence of 4 problems (P) during each of 7 daily sessions. Performance was evaluated 20 min after SC injection of either DIZO-0.025, 0.05, 0.125 mg/kg, or SAL. The 0.125-mg/kg dose caused extreme motor ataxia which precluded testing during that session. The 0.05-mg/kg but not the 0.025-mg/kg dose significantly disrupted performance on both error and trials to criterion measures. Both problem and interaction effects were significant. Disruption was most evident on two specific problems, those involving a side change from the first to second detour. Also, rats had more difficulty switching sides from problem to problem (few errors on P-1 and most on P-4), suggesting proactive interference effects. In sum, DIZO was observed to significantly disrupt performance in both mazes in a dose-related manner similar to effects observed in previous studies following administration of the anticholinergic drug scopolamine. For the 14-unit T-maze, the present results simulate age-related deficits previously found in acquisition of that task. C1 NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NIA, NATHAN W SHOCK LABS, BALTIMORE, MD 21224 USA. ESSEX COMMUNITY COLL, BALTIMORE, MD 21237 USA. NR 39 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1991 VL 40 IS 4 BP 949 EP 958 DI 10.1016/0091-3057(91)90111-E PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GW603 UT WOS:A1991GW60300038 PM 1667826 ER PT J AU PEPPERBERG, DR OKAJIMA, TIL RIPPS, H CHADER, GJ WIGGERT, B AF PEPPERBERG, DR OKAJIMA, TIL RIPPS, H CHADER, GJ WIGGERT, B TI FUNCTIONAL-PROPERTIES OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Note ID ROD OUTER SEGMENTS; PIGMENT-EPITHELIUM; BOVINE RETINA; IRBP; MECHANISM; LIPOSOMES; RD AB It has been hypothesized that interphotoreceptor retinoid-binding protein (IRBP) functions as a two-way carrier of retinoid between the retinal pigment epithelium (RPE) and rod photoreceptors in the vertebrate eye. This hypothesis has been tested in recent studies that have employed purified, initially ligand-free, bovine IRBP and the "RPE-eyecup" obtained from the toad (Bufo marinus) eye. The present experiments further characterize the IRBP/RPE-eyecup system with respect to (i) the solubilization and protection of retinol by IRBP, and (ii) the time course of IRBP-mediated release of 11-cis retinal by the RPE. The data, together with previous findings in the IRBP/RPE-eyecup preparation, support the view that 11-cis retinal is the principal retinoid released by the RPE into IRBP-supplemented aqueous medium, and that IRBP in vivo promotes the regeneratiOn of rhodopsin by facilitating the exchange of retinoid between bleached rods and the RPE. C1 NEI,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,DEPT ANAT CELL BIOL,CHICAGO,IL 60612. RP PEPPERBERG, DR (reprint author), UNIV ILLINOIS,COLL MED,LIONS ILLINOIS EYE RES INST,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60612, USA. FU NEI NIH HHS [EY-05494, EY-01792, EY-06516] NR 26 TC 80 Z9 81 U1 1 U2 2 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 DEC PY 1991 VL 54 IS 6 BP 1057 EP 1060 DI 10.1111/j.1751-1097.1991.tb02129.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GU368 UT WOS:A1991GU36800024 PM 1775528 ER PT J AU TALON, M ZEEVAART, JAD GAGE, DA AF TALON, M ZEEVAART, JAD GAGE, DA TI IDENTIFICATION OF GIBBERELLINS IN SPINACH AND EFFECTS OF LIGHT AND DARKNESS ON THEIR LEVELS SO PLANT PHYSIOLOGY LA English DT Article ID ZEA-MAYS-L; ENDOGENOUS GIBBERELLINS; PISUM-SATIVUM; ARABIDOPSIS-THALIANA; PARTIAL-PURIFICATION; INTERNODE LENGTH; PHOTOPERIOD; METABOLISM; SHOOTS; SEEDS AB The endogenous gibberellin (GA) content ot spinach (Spinacia oleracea) was reinvestigated by combined gas chromatography-mass spectrometry analysis. The 13-hydroxy GAs: GA53, GA44, GA19, GA17, GA20, GA5, GA1, GA29, and GA8; the non-3,13-hydroxy GAs: GA12, GA15, GA9, and GA51; and the 3-beta-hydroxy GAs: GA4, GA7, and GA34, were identified in spinach extracts by comparing full-scan mass spectra and Kovats retention indices with those of reference GAs. In addition, spinach plants contained GA7-isolactone, 16,17-dihydro-17-hydroxy-GA53, GA29-catabolite, 3-epi-GA1, and 10 uncharacterized GAs with mass spectra indicative of mono- and dihydroxy-GA12, monohydroxy-GA25, dihydroxy-GA24, and dihydroxy-GA9. The effect of light-dark conditions on the GA levels of the 13-hydroxylation pathway was studied by using labeled internal standards in selected ion monitoring mode. In short day, the GA levels were higher at the end of the light period than at the end of the dark period. Levels of GAs at the end of each short day were relatively constant. During the first supplementary light period of long day treatment, GA53 and GA19 declined dramatically, GA44 and GA1 decreased slightly, and GA20 increased. During the subsequent high-intensity light period, the GA20 level decreased and the levels of GA53, GA44, GA19, and GA1 increased slightly. Within 7 days after the beginning of long day treatment, similar patterns for GA53 and GA19 occurred. Furthermore, when these plants were transferred to darkness, an increase in the levels of GA53 and GA19 was observed. These results are compatible with the idea that in spinach, the flow through the GA biosynthetic pathway is much enhanced during the high-intensity light period, although GA turnover occurs also during the supplementary period of long day, both effects being responsible for the increase of GA20 and GA1 in long day. C1 MICHIGAN STATE UNIV,US DOE,PLANT RES LAB,E LANSING,MI 48824. MICHIGAN STATE UNIV,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. RP ZEEVAART, JAD (reprint author), MICHIGAN STATE UNIV,US DOE,PLANT RES LAB,E LANSING,MI 48824, USA. RI Talon, Manuel/C-8540-2014 OI Talon, Manuel/0000-0003-4291-9333 NR 25 TC 61 Z9 61 U1 0 U2 4 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 1991 VL 97 IS 4 BP 1521 EP 1526 DI 10.1104/pp.97.4.1521 PG 6 WC Plant Sciences SC Plant Sciences GA GU884 UT WOS:A1991GU88400038 PM 16668579 ER PT J AU HERMOUET, S MERENDINO, JJ GUTKIND, JS SPIEGEL, AM AF HERMOUET, S MERENDINO, JJ GUTKIND, JS SPIEGEL, AM TI ACTIVATING AND INACTIVATING MUTATIONS OF THE ALPHA-SUBUNIT OF GI2 PROTEIN HAVE OPPOSITE EFFECTS ON PROLIFERATION OF NIH 3T3 CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GUANINE NUCLEOTIDE-BINDING PROTEINS; SITE-DIRECTED MUTAGENESIS; STABLE TRANSFECTION; ADP-RIBOSYLATION ID GTP-BINDING PROTEIN; ADENYLYL CYCLASE; PERTUSSIS TOXIN; GS-ALPHA; SYNTHETIC PEPTIDES; INHIBITION; RECEPTOR; STIMULATION; FIBROBLASTS; ANTIBODIES AB Previous studies have demonstrated that mutations of highly conserved residues in the alpha-subunit of G(s) (alpha(s)) can inhibit either the intrinsic GTPase activity (glutamine-227 to leucine, Q227L) or the ability of the protein to be activated by GTP (glycine-226 to alanine, G226A). We stably transfected NIH 3T3 cells with cDNAs encoding G(i2) alpha-subunit (alpha(i2)) containing either wild-type sequence or the homologous mutations Q205L and G204A. High expression of wild-type alpha(i2) Q205L alpha(i2), and G204A alpha(i2) was confirmed in transfected cells by immunoblot analysis. The overexpression of all three alpha(i2) proteins was accompanied by an increase in beta-subunit expression. Q205L alpha(i2) was a poor substrate for ADP-ribosylation by pertussis toxin as compared with wild-type alpha(i2). Expression of Q205L alpha(i2) markedly decreased forskolin- or cholera toxin-stimulated intracellular cAMP levels in intact cells, confirming the constitutively activated state of the protein. In contrast, G204A alpha(i2) increased intracellular cAMP and was resistant to guanosine 5'-[gamma-thio]triphosphate-induced inhibition of ADP-ribosylation by pertussis toxin, as expected for an inactive alpha(i2). Transfection of wild-type, Q205L, or G204A alpha(i2) cDNA did not induce focus formation of NIH 3T3 cells. However, overexpression of Q205L alpha(i2) induced a decreased serum requirement, a reduced doubling time, and an 8- to 10-fold increase in [H-3]thymidine incorporation. Q205L alpha(i2) cells formed small colonies in soft agar, demonstrating some degree of anchorage-independent proliferation. Expression of G204A alpha(i2) slowed the growth of NIH 3T3 cells. We conclude that alpha(i2) plays an important role in regulation of fibroblast growth. C1 NIDR,CELL DEV & ONCOL LAB,BETHESDA,MD 20892. RP HERMOUET, S (reprint author), NIADDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8D17,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009 NR 40 TC 124 Z9 125 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 DEC PY 1991 VL 88 IS 23 BP 10455 EP 10459 DI 10.1073/pnas.88.23.10455 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000017 PM 1660138 ER PT J AU NUSSINOV, R WOLFSON, HJ AF NUSSINOV, R WOLFSON, HJ TI EFFICIENT DETECTION OF 3-DIMENSIONAL STRUCTURAL MOTIFS IN BIOLOGICAL MACROMOLECULES BY COMPUTER VISION TECHNIQUES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 3-DIMENSIONAL STRUCTURAL COMPARISON; CRYSTALLOGRAPHIC COORDINATES; EFFICIENT COMPUTER VISION ALGORITHM; MACROMOLECULAR STRUCTURE ANALYSIS ID OBJECT RECOGNITION; DNA-BINDING; B-DNA; PROTEIN; SEQUENCE; HISTONE AB Macromolecules carrying biological information often consist of independent modules containing recurring structural motifs. Detection of a specific structural motif within a protein (or DNA) aids in elucidating the role played by the protein (DNA element) and the mechanism of its operation. The number of crystallographically known structures at high resolution is increasing very rapidly. Yet, comparison of three-dimensional structures is a laborious time-consuming procedure that typically requires a manual phase. To date, there is no fast automated procedure for structural comparisons. We present an efficient O(n3) worst case time complexity algorithm for achieving such a goal (where n is the number of atoms in the examined structure). The method is truly three-dimensional, sequence-order-independent, and thus insensitive to gaps, insertions, or deletions. This algorithm is based on the geometric hashing paradigm, which was originally developed for object recognition problems in computer vision. It introduces an indexing approach based on transformation invariant representations and is especially geared toward efficient recognition of partial structures in rigid objects belonging to large data bases. This algorithm is suitable for quick scanning of structural data bases and will detect a recurring structural motif that is a priori unknown. The algorithm uses protein (or DNA) structures, atomic labels, and their three-dimensional coordinates. Additional information pertaining to the structure speeds the comparisons. The algorithm is straightforwardly parallelizable, and several versions of it for computer vision applications have been implemented on the massively parallel connection machine. A prototype version of the algorithm has been implemented and applied to the detection of substructures in proteins. C1 TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES FACIL,MATH BIOL LAB,FREDERICK,MD 21702. NYU,COURANT INST MATH SCI,ROBOT RES LAB,NEW YORK,NY 10003. RP NUSSINOV, R (reprint author), TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 NR 43 TC 191 Z9 196 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC PY 1991 VL 88 IS 23 BP 10495 EP 10499 DI 10.1073/pnas.88.23.10495 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000025 PM 1961713 ER PT J AU SMITH, CD CARNEY, JM STARKEREED, PE OLIVER, CN STADTMAN, ER FLOYD, RA MARKESBERY, WR AF SMITH, CD CARNEY, JM STARKEREED, PE OLIVER, CN STADTMAN, ER FLOYD, RA MARKESBERY, WR TI EXCESS BRAIN PROTEIN OXIDATION AND ENZYME DYSFUNCTION IN NORMAL AGING AND IN ALZHEIMER-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INACTIVATION PRECEDES PROTEOLYSIS; BACTERIAL GLUTAMINE-SYNTHETASE; FREE-RADICALS; SUPEROXIDE-DISMUTASE; TURNOVER; PEROXIDASE; OXIDASE AB The relationship between Alzheimer disease (AD) and aging is not currently known. In this study, postmortem frontal- and occipital-pole brain samples were obtained from 16 subjects with AD, 8 age-matched controls, and 5 young controls. These samples were analyzed both for protein oxidation products (carbonyl) and the activities of two enzymes vulnerable to mixed-function oxidation, glutamine synthetase and creatine kinase. Glutamine synthetase is more sensitive to mixed-function oxidation than creatine kinase. Carbonyl content rises exponentially with age, at double the rate in the frontal pole compared with the occipital pole. Compared with young controls, both aged groups (AD and age-matched controls) have increased carbonyl content and decreased glutamine synthetase and creatine kinase activities, which are more marked in the frontal than occipital pole in all instances. We conclude that protein oxidation products accumulate in the brain and that oxidation-vulnerable enzyme activities decrease with aging in the same regional pattern (frontal more affected than occipital). However, only glutamine synthetase activity distinguishes AD from age-matched controls: Because glutamine synthetase activity is differentially reduced in the frontal pole in AD, we suggest that AD may represent a specific brain vulnerability to age-related oxidation. C1 UNIV KENTUCKY,MED CTR,SANDERS BROWN CTR AGING,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT PHARMACOL,LEXINGTON,KY 40536. GEORGE WASHINGTON UNIV,SCH MED,DEPT EXPTL MED,WASHINGTON,DC 20037. MERCK & CO INC,RAHWAY,NJ 07065. NHLBI,BIOCHEM LAB,BETHESDA,MD 20205. OKLAHOMA MED RES FDN,MOLEC TOXICOL RES GRP,OKLAHOMA CITY,OK 73104. RP SMITH, CD (reprint author), UNIV KENTUCKY,COLL MED,MED CTR,DEPT NEUROL,800 ROSE ST,LEXINGTON,KY 40536, USA. FU NIA NIH HHS [AG060960, IP50-AG05144]; NINDS NIH HHS [NS23307] NR 41 TC 963 Z9 985 U1 10 U2 35 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 DEC PY 1991 VL 88 IS 23 BP 10540 EP 10543 DI 10.1073/pnas.88.23.10540 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000034 PM 1683703 ER PT J AU SINGH, G KAUR, S STOCK, JL JENKINS, NA GILBERT, DJ COPELAND, NG POTTER, SS AF SINGH, G KAUR, S STOCK, JL JENKINS, NA GILBERT, DJ COPELAND, NG POTTER, SS TI IDENTIFICATION OF 10 MURINE HOMEOBOX GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DEGENERATE OLIGONUCLEOTIDE SCREENING; MOUSE DEVELOPMENT; HOMEODOMAIN SEQUENCE COMPARISON ID MOLECULAR-STRUCTURE; ANTENNAPEDIA-CLASS; SEQUENCE HOMOLOGY; CARCINOMA-CELLS; DNA-SEQUENCES; DROSOPHILA; MOUSE; EXPRESSION; COMPLEX; EMBRYOGENESIS AB In Drosophila a number of genes important in establishing segmentation patterns and in determining segment identities have been shown to carry the homeobox sequence. Over 30 murine homeobox genes have been cloned, many on the basis of sequence homology to Drosophila prototypes. Here we report the cloning and sequencing of 10 new and 6 previously known homeobox genes by screening a murine genomic library with a 768-fold degenerate oligonucleotide corresponding to the most conserved 8-amino acid motif in the recognition helix of the homeodomain. Eight of these new homeobox genes have been chromosomally mapped. Four genes do not belong to any of the known homeobox gene clusters but instead map to new locations on chromosome 1 (single gene) and chromosome 5 (three genes). Sequence comparisons indicate that two of these are very closely related and represent a distinct new category of homeobox genes. The remaining four mapped genes reside in previously established murine homeobox gene clusters. Specifically, two map to the cluster HOX-1 on chromosome 6 and one each to HOX-3 and HOX-4 on chromosome 15 and 2, respectively. The ratio of newly identified homeobox genes to the previously characterized murine homeobox genes suggests that there remain several uncharacterized homeobox genes in the murine genome. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP SINGH, G (reprint author), CHILDRENS HOSP MED CTR,DEPT BASIC SCI,ELLAND & BETHESDA AVE,CINCINNATI,OH 45229, USA. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD24517] NR 45 TC 74 Z9 82 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 DEC PY 1991 VL 88 IS 23 BP 10706 EP 10710 DI 10.1073/pnas.88.23.10706 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000069 PM 1683707 ER PT J AU JACOBOMOLINA, A CLARK, AD WILLIAMS, RL NANNI, RG CLARK, P FERRIS, AL HUGHES, SH ARNOLD, E AF JACOBOMOLINA, A CLARK, AD WILLIAMS, RL NANNI, RG CLARK, P FERRIS, AL HUGHES, SH ARNOLD, E TI CRYSTALS OF A TERNARY COMPLEX OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE WITH A MONOCLONAL-ANTIBODY FAB FRAGMENT AND DOUBLE-STRANDED DNA DIFFRACT X-RAYS TO 3.5-A RESOLUTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIBODY COCRYSTALLIZATION; DNA COCRYSTALLIZATION; AIDS; POLYMERASE STRUCTURE; PROTEIN NUCLEIC ACID INTERACTION ID ESCHERICHIA-COLI; HIV-1 REPLICATION; CRYSTALLIZATION; INHIBITION; EXPRESSION AB Two crystal forms of complexes have been grown that contain human immunodeficiency virus type 1 reverse transcriptase and a monoclonal antibody Fab fragment. One of the crystal forms (form II, space group P3(1)12, a = 168.7 angstrom, c = 220.3 angstrom) diffracts x-rays to 3.5-angstrom resolution and appears suitable for moderate-resolution structure determination. The form II crystals have the unusual property that their maximum resolution of diffraction and resistance to radiation damage are enhanced by either crystallization in the presence of or soaking with double-stranded DNA primer-template mimics. These crystals may permit structural studies of catalytically relevant complexes and eventually enable us to experimentally observe successive steps in the reverse transcription process. C1 RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. RP JACOBOMOLINA, A (reprint author), CTR ADV BIOTECHNOL & MED,1679 HOES LANE,PISCATAWAY,NJ 08854, USA. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI26790]; NIGMS NIH HHS [GM39558] NR 23 TC 54 Z9 55 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 DEC PY 1991 VL 88 IS 23 BP 10895 EP 10899 DI 10.1073/pnas.88.23.10895 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000108 PM 1720554 ER PT J AU GOLDFARB, LG BROWN, P MCCOMBIE, WR GOLDGABER, D SWERGOLD, GD WILLS, PR CERVENAKOVA, L BARON, H GIBBS, CJ GAJDUSEK, DC AF GOLDFARB, LG BROWN, P MCCOMBIE, WR GOLDGABER, D SWERGOLD, GD WILLS, PR CERVENAKOVA, L BARON, H GIBBS, CJ GAJDUSEK, DC TI TRANSMISSIBLE FAMILIAL CREUTZFELDT-JAKOB DISEASE ASSOCIATED WITH 5, 7, AND 8 EXTRA OCTAPEPTIDE CODING REPEATS IN THE PRNP GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMYLOID PRECURSOR PROTEIN; PRION PROTEIN ID GERSTMANN-STRAUSSLER SYNDROME; PRION PROTEIN GENE; SCHEINKER SYNDROME; INSERTION; SEQUENCES; DIAGNOSIS; DEMENTIA; ELASTIN AB The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of rive variant tandem octapeptide coding repeats between codons 51 and 91. We screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. We identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had "wobble" nucleotide substitutions. We also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD. C1 NINCDS,RECEPTOR BIOCHEM & MOLEC BIOL SECT,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. NCI,DIV CANC BIOL & DIAG,BIOCHEM LAB,BETHESDA,MD 20892. UNIV AUCKLAND,DEPT PHYS,AUCKLAND,NEW ZEALAND. INST PREVENT & CLIN MED,BRATISLAVA,CZECHOSLOVAKIA. SEARLE PHARMACEUT,PARIS,FRANCE. RP GOLDFARB, LG (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892, USA. RI Wills, Peter/B-9611-2012 NR 40 TC 268 Z9 276 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC PY 1991 VL 88 IS 23 BP 10926 EP 10930 DI 10.1073/pnas.88.23.10926 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT480 UT WOS:A1991GT48000115 PM 1683708 ER PT J AU PIKE, SE MARKEY, SP IJAMES, C JONES, KD TOSATO, G AF PIKE, SE MARKEY, SP IJAMES, C JONES, KD TOSATO, G TI THE ROLE OF LACTIC-ACID IN AUTOCRINE B-CELL GROWTH-STIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPSTEIN-BARR VIRUS; L-LACTATE; GLUCOSE; PURIFICATION; TRANSPORT AB Growth and survival of Epstein-Barr virus (EBV)-immortalized B lymphocytes cultured at low cell densities require autocrine soluble factors. In this study, we have purified a low molecular weight autocrine soluble factor that promotes growth of EBV-immortalized B cells in serum-free conditions and identified it as lactic acid (LA). Synthetic LA stimulated growth in EBV-immortalized B cells at 1-10 mM, a concentration of LA measured in the culture supernatant of EBV-immortalized cell lines. LA alone was found to account for > 70% of the autocrine growth factor activity in serum-free supernatants of EBV-immortalized B cells. Aminooxyacetate, a glutamate-oxaloacetate transaminase inhibitor, specifically inhibited B-cell growth induced by LA, suggesting that this process requires mitochondrial-cytosol transfers. Thus, LA is an autocrine stimulatory molecule that in serum-free conditions is essential for the continuous proliferation of EBV-immortalized B cells. This represents an unexpected function for LA. C1 NIH,CLIN SCI LAB,BETHESDA,MD 20892. RP PIKE, SE (reprint author), US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 26 Z9 26 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 DEC PY 1991 VL 88 IS 24 BP 11081 EP 11085 DI 10.1073/pnas.88.24.11081 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700021 PM 1662382 ER PT J AU KRSMANOVIC, LZ STOJILKOVIC, SS BALLA, T ALDAMLUJI, S WEINER, RI CATT, KJ AF KRSMANOVIC, LZ STOJILKOVIC, SS BALLA, T ALDAMLUJI, S WEINER, RI CATT, KJ TI RECEPTORS AND NEUROSECRETORY ACTIONS OF ENDOTHELIN IN HYPOTHALAMIC NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GONADOTROPIN-RELEASING HORMONE NEURON RECEPTORS; INOSITOL PHOSPHOLIPID HYDROLYSIS; GONADOTROPIN-RELEASING HORMONE SECRETION ID RAT HYPOTHALAMUS; VASOCONSTRICTOR PEPTIDE; BINDING-SITES; CELLS; PITUITARY; RELEASE; BRAIN; VISUALIZATION; SARAFOTOXIN; EXPRESSION AB Primary cultures of rat hypothalamic neurons were found to secrete the potent calcium-mobilizing and mitogenic peptide endothelin (ET) and to contain specific ET binding sites with higher affinity for ET-1 and ET-2 than ET-3. ET receptors of similar specificity were also identified in two gonadotropin-releasing hormone (GnRH) neuronal cell lines (GT1-1 and GT1-7). In both primary cultures and GnRH neurons, receptor binding of ETs led to marked and dose-dependent increases of inositol phosphates; inositol bis-, tris-, and tetrakisphosphates increased promptly, reached a peak within 2 min, and returned toward the steady-state levels during the next 10 min. ET-1 was more potent than ET-3 in mobilizing inositol phosphates, consistent with its greater affinity for the ET receptors in these cells. ET also stimulated GnRH secretion from perifused hypothalamic cultures and GnRH cell lines, with a sharp increase followed by a prompt decline to the basal level. These data show that ET is produced in the hypothalamus and acts through calcium-mobilizing ET receptors in normal and transformed secretory neurons to stimulate GnRH release. These actions of locally produced ETs upon GnRH-secreting neurons indicate that the vasoconstrictor peptides have the capacity to regulate neurosecretion and could participate in the hypothalamic control of anterior pituitary function and gonadotropin secretion. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,CTR REPROD ENDOCRINOL,SAN FRANCISCO,CA 94143. RP CATT, KJ (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 31 TC 84 Z9 86 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 DEC PY 1991 VL 88 IS 24 BP 11124 EP 11128 DI 10.1073/pnas.88.24.11124 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700030 PM 1662384 ER PT J AU USDIN, TB MEZEY, E CHEN, C BROWNSTEIN, MJ HOFFMAN, BJ AF USDIN, TB MEZEY, E CHEN, C BROWNSTEIN, MJ HOFFMAN, BJ TI CLONING OF THE COCAINE-SENSITIVE BOVINE DOPAMINE TRANSPORTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROTRANSMITTER UPTAKE; SUBSTANTIA NIGRA; CENTRAL NERVOUS SYSTEM ID NOREPINEPHRINE UPTAKE SITES; BRAIN GABA TRANSPORTER; UPTAKE INHIBITOR; RNA-POLYMERASE; EXPRESSION; SEQUENCE; SYSTEM; GENES; CDNA AB A cDNA encoding the dopamine transporter from bovine brain substantia nigra was identified on the basis of its structural homology to other, recently cloned, neurotransmitter transporters. The sequence of the 693-amino acid protein is quite similar to those of the rat gamma-aminobutyric acid, human norepinephrine, and rat serotonin transporters. Dopamine transporter mRNA was detected by in situ hybridization in the substantia nigra but not in the locus coeruleus, raphe, caudate, or other brain areas. [H-3]Dopamine accumulation in tissue culture cells transfected with the cDNA was inhibited by amphetamine, cocaine, and specific inhibitors of dopamine transport, including GBR12909. C1 SEMMELWEIS UNIV MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. RP USDIN, TB (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009 NR 38 TC 213 Z9 214 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC PY 1991 VL 88 IS 24 BP 11168 EP 11171 DI 10.1073/pnas.88.24.11168 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700039 PM 1722321 ER PT J AU WEI, SJC CHANG, RL WONG, CQ BHACHECH, N CUI, XX HENNIG, E YAGI, H SAYER, JM JERINA, DM PRESTON, BD CONNEY, AH AF WEI, SJC CHANG, RL WONG, CQ BHACHECH, N CUI, XX HENNIG, E YAGI, H SAYER, JM JERINA, DM PRESTON, BD CONNEY, AH TI DOSE-DEPENDENT DIFFERENCES IN THE PROFILE OF MUTATIONS INDUCED BY AN ULTIMATE CARCINOGEN FROM BENZO[A]PYRENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BENZO[A]PYRENE DIOL EPOXIDE; HYPOXANTHINE (GUANINE) PHOSPHORIBOSYLTRANSFERASE; V-79 CELLS; CHEMICAL MUTAGENESIS ID OPTICAL ENANTIOMERS; SHUTTLE VECTOR; HUMAN-CELLS; DNA; 7,8-DIOL-9,10-EPOXIDES; ADDUCTS; KINDS; (+/-)-7-BETA,8-ALPHA-DIHYDROXY-9-ALPHA,10-ALPHA-EPOXY-7,8,9,10-TETRAHYDR OBENZO<.; EPOXIDE; GENE AB Mutations in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-79 cells were examined after exposure of the cells to a high cytotoxic dose (0.48-mu-M; 35% survival) and a low noncytotoxic dose (0.04-mu-M; 100% survival) of the ultimate carcinogen (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BPDE]. Independent 8-azaguanine-resistant colonies were isolated and cDNAs were prepared by reverse transcription. The coding region of the cDNA of the HPRT gene was amplified by the polymerase chain reaction and sequenced. An examination of the DNA base sequence changes induced by different doses of (+)-BPDE demonstrated that the high dose of (+)-BPDE caused base substitution mutations almost exclusively at G-C base pairs whereas the low dose of (+)-BPDE caused mutations at both G.C and A.T base pairs. Thus, use of a low dose of (+)-BPDE allowed the detection of mutations (at A.T base pairs) that were not readily observed with a high dose of (+)-BPDE. The data also suggest that the low dose of (+)-BPDE may have caused a different profile of base substitutions at G.C base pairs and exon deletions than the high dose. The results indicate dose-dependent differences in the profile of mutations for an ultimate carcinogen. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP WEI, SJC (reprint author), RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08854, USA. FU NCI NIH HHS [CA49756]; NIEHS NIH HHS [ES05022] NR 24 TC 99 Z9 100 U1 2 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 DEC PY 1991 VL 88 IS 24 BP 11227 EP 11230 DI 10.1073/pnas.88.24.11227 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700051 PM 1763036 ER PT J AU COOK, JC CHOCK, PB AF COOK, JC CHOCK, PB TI ASSOCIATION OF UBIQUITIN-ACTIVATING ENZYME WITH HELA-CELL CHROMOSOMES DURING MITOSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONJUGATING ENZYME; CONDENSATION; CYCLE; PHOSPHORYLATION; DISAPPEARANCE; METABOLISM; HISTONES; PROTEINS; ENCODES; 2B AB Ubiquitin-activating enzyme (E1) is the first enzyme in the pathway leading to formation of ubiquitin-protein conjugates. Antibodies raised against E1 were affinity purified and used for immunostaining HeLa cells. Condensed chromosomes in mitotic cells were found to be strongly immunoreactive. Chromosomes from metaphase-arrested HeLa cells were isolated and chromosome-associated proteins were analyzed by Western blotting. E1 was detected in fractions containing isolated chromosomes. These results suggest that E1 is associated with condensed chromosomes during mitosis. RP COOK, JC (reprint author), NHLBI,BIOCHEM LAB,METAB REGULAT SECT,BETHESDA,MD 20892, USA. NR 35 TC 7 Z9 7 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 DEC PY 1991 VL 88 IS 24 BP 11388 EP 11392 DI 10.1073/pnas.88.24.11388 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700084 PM 1763053 ER PT J AU MILLAN, MA JACOBOWITZ, DM AGUILERA, G CATT, KJ AF MILLAN, MA JACOBOWITZ, DM AGUILERA, G CATT, KJ TI DIFFERENTIAL DISTRIBUTION OF AT1 AND AT2 ANGIOTENSIN-II RECEPTOR SUBTYPES IN THE RAT-BRAIN DURING DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AUTORADIOGRAPHY; CIRCUMVENTRICULAR ORGANS; THALAMUS ID IMMUNOCYTOCHEMICAL LOCALIZATION; FETAL BRAIN; SYSTEM; EXISTENCE; EXPRESSION; CULTURES; CELLS AB Angiotensin II (AII) receptor subtypes were analyzed in the brains of adult and 2-week-old rats by in vitro autoradiography with I-125-labeled [Sar1,Ile8]AII and competition studies with three AII antagonists: the nonpeptide antagonist, DuP 753, which is specific for AT1 receptors that mediate the calcium-inositol phospholipid signaling actions of AII; and nonpeptide (PD 123177) and peptide (CGP 42112A) antagonists that are selective for AT2 receptors of yet unknown function. In the adult rat brain, DuP 753 inhibited radioligand binding to the circumventricular organs and paraventricular nucleus but not to the lateral septum, subthalamic nucleus, and inferior olive. However, binding of I-125-labeled [Sar1,Ile8]AII in the latter regions was inhibited by the AT2 receptor antagonists PD 123177 and CGP 42112A. These areas showed similar displacement by the AT2 receptor subtype-specific antagonists in 2-week-old rats. In addition, radioligand binding at multiple sites of transient expression of AII receptors in 2-week-old rats, including several thalamic nuclei, the nuclei of the 3rd and 12th cranial nerves, geniculate bodies, cerebellum, and cingulate cortex, was displaced by the AT2 antagonists but not by DuP 753. These studies have demonstrated the presence of two AII receptor subtypes in the brain, one (AT1) in areas related to regulation of blood pressure, water intake, and pituitary hormone secretion, and one (AT2) whose function is not yet defined. The abundance and location of brain AT2 receptors in young animals, and the age-related changes in relative expression of the receptor subtypes, suggest that All exerts specific actions according to the developmental stage of the central nervous system. C1 NICHHD,ENDOCRINOL & REPROD BRANCH,BLDG 10,ROOM B1-L400,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP CATT, KJ (reprint author), NICHHD,ENDOCRINOL & REPROD BRANCH,BLDG 10,ROOM B1-L400,BETHESDA,MD 20892, USA. NR 33 TC 161 Z9 161 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 DEC PY 1991 VL 88 IS 24 BP 11440 EP 11444 DI 10.1073/pnas.88.24.11440 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700095 PM 1763058 ER PT J AU NISHIMURA, H SALTIS, J HABBERFIELD, AD GARTY, NB GREENBERG, AS CUSHMAN, SW LONDOS, C SIMPSON, IA AF NISHIMURA, H SALTIS, J HABBERFIELD, AD GARTY, NB GREENBERG, AS CUSHMAN, SW LONDOS, C SIMPSON, IA TI PHOSPHORYLATION STATE OF THE GLUT4 ISOFORM OF THE GLUCOSE TRANSPORTER IN SUBFRACTIONS OF THE RAT ADIPOSE CELL - EFFECTS OF INSULIN, ADENOSINE, AND ISOPROTERENOL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LIPOLYTIC HORMONES; ANTILIPOLYTIC HORMONES; CYCLIC AMP-DEPENDENT PROTEIN KINASE ID DEPENDENT PROTEIN-KINASE; PLASMA-MEMBRANE; APPARENT TRANSLOCATION; POTENTIAL MECHANISM; PHORBOL ESTER; ADIPOCYTES; STIMULATION; SYSTEMS; INVITRO; INHIBITION AB The acute effects of insulin, adenosine, and isoproterenol on the activity, subcellular distribution, and phosphorylation state of the GLUT4 glucose transporter isoform were investigated in rat adipocytes under conditions carefully controlled to monitor changes in cAMP-dependent protein kinase (A-kinase) activity. In contrast to GLUT1, which has not been shown to be phosphorylated even when cells are exposed to any of the above agents, GLUT4 was partially phosphorylated (0.1-0.2 mol/mol) when the activity of the A-kinase was suppressed, and remained unchanged in response to insulin. Isoproterenol elicited a 64% inhibition of insulin-stimulated glucose transport activity in the absence, but not the presence, of adenosine receptor agonists. However, in either the presence or the absence of agonists, A-kinase was activated as assessed by examining the phosphorylation of the major adipocyte A-kinase substrate, perilipin. Similarly, under either condition, phosphorylation of GLUT4 was enhanced 1.4-fold in the intracellular membranes, but no significant change was observed in the plasma membrane. In the absence of adenosine receptor agonists, isoproterenol exerted a small (14%) but significant inhibition of the insulin-induced translocation of GLUT4 but had no effect on the translocation of GLUT1. Thus, changes in the phosphorylation state and/or subcellular distribution of GLUT4 cannot account for the inhibition of insulin-stimulated glucose activity induced by isoproterenol. C1 NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BLDG 10,ROOM 5N102,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,MEMBRANE REGULAT SECT,BETHESDA,MD 20892. RP SIMPSON, IA (reprint author), NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BLDG 10,ROOM 5N102,BETHESDA,MD 20892, USA. NR 32 TC 44 Z9 45 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 DEC PY 1991 VL 88 IS 24 BP 11500 EP 11504 DI 10.1073/pnas.88.24.11500 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV877 UT WOS:A1991GV87700107 PM 1763064 ER PT J AU SCHNEIDER, SF AF SCHNEIDER, SF TI NO FLUORIDE IN OUR FUTURE SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article RP SCHNEIDER, SF (reprint author), NIMH,DIV BASIC BRAIN & BEHAV SCI,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 1991 VL 22 IS 6 BP 456 EP 460 DI 10.1037//0735-7028.22.6.456 PG 5 WC Psychology, Multidisciplinary SC Psychology GA GT785 UT WOS:A1991GT78500004 ER PT J AU HORWITZ, B SWEDO, SE GRADY, CL PIETRINI, P SCHAPIRO, MB RAPOPORT, JL RAPOPORT, SI AF HORWITZ, B SWEDO, SE GRADY, CL PIETRINI, P SCHAPIRO, MB RAPOPORT, JL RAPOPORT, SI TI CEREBRAL METABOLIC PATTERN IN OBSESSIVE-COMPULSIVE DISORDER - ALTERED INTERCORRELATIONS BETWEEN REGIONAL RATES OF GLUCOSE-UTILIZATION SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; CORRELATION ANALYSIS; GLUCOSE METABOLISM; BRAIN ID BRAIN-REGIONS; NEUROSIS; MODEL; DEPRESSION; ALZHEIMERS; AUTISM; ADULTS AB Correlations between normalized regional cerebral metabolic rates for glucose, determined by positron emission tomography with F-18-2-fluoro-2-deoxy-D-glucose, were used to investigate functional associations between pairs of brain regions in 18 adult patients with primary obsessive-compulsive disorder (OCD) of childhood-onset, as compared with 18 age- and sex-matched control subjects. The number of correlations that differed significantly between the two groups exceeded chance, although as many of these correlations were larger in the OCD group relative to controls as were smaller. The two regions that had the largest number of correlations that differed significantly between groups were a left hemisphere superior parietal region and the left hemisphere anterior medial temporal area (which includes principally the amygdala). Correlations involving the caudate nuclei did not differ between the two groups for the most part. Anterior limbic/paralimbic regions had correlations in the OCD group that were significantly larger with frontal areas than in controls, and correlations that were significantly smaller with posterior brain regions. This pattern was especially pronounced for the left hemisphere anterior medial temporal region. These results suggest that the correlation pattern in OCD is not characterized by an overall loss of functional integration but, rather, by functional reorganization. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,POSITRON EMISS TOMOG UNIT,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BRAIN AGING & DEMENTIA SECT,BETHESDA,MD 20892. RP HORWITZ, B (reprint author), NIA,NEUROSCI LAB,BRAIN IMAGING & COMP UNIT,BLDG 10,RM 6C-414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 58 TC 51 Z9 51 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC PY 1991 VL 40 IS 4 BP 221 EP 237 DI 10.1016/0925-4927(91)90014-H PG 17 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HK181 UT WOS:A1991HK18100002 PM 1811240 ER PT J AU GLOSSER, G FRIEDMAN, RB AF GLOSSER, G FRIEDMAN, RB TI LEXICAL BUT NOT SEMANTIC PRIMING IN ALZHEIMERS-DISEASE SO PSYCHOLOGY AND AGING LA English DT Article ID MEMORY; DEMENTIA; IMPAIRMENT; DECISION; TASK C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. RP GLOSSER, G (reprint author), GRAD HOSP PHILADELPHIA,DEPT NEUROL,1 GRAD PLAZA,PHILADELPHIA,PA 19146, USA. FU NINDS NIH HHS [NS-06209] NR 34 TC 42 Z9 42 U1 4 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1991 VL 6 IS 4 BP 522 EP 527 DI 10.1037/0882-7974.6.4.522 PG 6 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA GV050 UT WOS:A1991GV05000004 PM 1777139 ER PT J AU BOUMPAS, DT YAMADA, H PATRONAS, NJ SCOTT, D KLIPPEL, JH BALOW, JE AF BOUMPAS, DT YAMADA, H PATRONAS, NJ SCOTT, D KLIPPEL, JH BALOW, JE TI PULSE CYCLOPHOSPHAMIDE FOR SEVERE NEUROPSYCHIATRIC LUPUS SO QUARTERLY JOURNAL OF MEDICINE LA English DT Article ID ERYTHEMATOSUS; THERAPY; MANIFESTATIONS; DIAGNOSIS; DISEASE AB We studied the effect of parenteral pulse cyclophosphamide therapy in nine patients with active systemic lupus erythematosus and severe central nervous system involvement. Seven patients had focal neurological deficits and/or seizures associated with abnormalities on cerebrospinal fluid analysis and/or magnetic resonance imaging. Two patients had organic brain syndrome with psychosis and normal cerebrospinal fluid and/or magnetic resonance imaging analysis. Six patients were unresponsive to treatment with high dose corticosteroid. Cyclophosphamide, 0.75-1.0 g/m2 body surface area, was administered intravenously every month for at least 2 months. Eight patients had a complete recovery or recovered with minor residuals. Cyclophosphamide was well tolerated with few side effects. We conclude that parenteral pulse cyclophosphamide is an effective adjunctive therapy for the management of patients with active systemic lupus erythematosus and central nervous system symptoms. C1 GEORGETOWN UNIV HOSP,DEPT RADIOL,WASHINGTON,DC 20007. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. RP BOUMPAS, DT (reprint author), NIDDKD,KIDNEY DIS SECT,BETHESDA,MD 20892, USA. NR 23 TC 103 Z9 106 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0033-5622 J9 Q J MED JI Q. J. Med. PD DEC PY 1991 VL 81 IS 296 BP 975 EP 984 DI 10.1093/qjmed/81.3.975 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA HE592 UT WOS:A1991HE59200003 PM 1808642 ER PT J AU PALMER, MH GERMAN, PS OUSLANDER, JG AF PALMER, MH GERMAN, PS OUSLANDER, JG TI RISK-FACTORS FOR URINARY-INCONTINENCE ONE YEAR AFTER NURSING-HOME ADMISSION SO RESEARCH IN NURSING & HEALTH LA English DT Article ID LONG-TERM CARE; PATHO-PHYSIOLOGY; HEALTH-CARE; FACILITIES; SYSTEM; IMPACT C1 JEWISH HOMES AGING GREATER LOS ANGELES,RESEDA,CA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. RP PALMER, MH (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,RM 3B06,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU PHS HHS [GAO 6765-04] NR 32 TC 42 Z9 42 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD DEC PY 1991 VL 14 IS 6 BP 405 EP 412 DI 10.1002/nur.4770140604 PG 8 WC Nursing SC Nursing GA GQ500 UT WOS:A1991GQ50000003 PM 1792342 ER PT J AU RILEY, JW RILEY, MW AF RILEY, JW RILEY, MW TI SOCIAL-SCIENCE AND THE ADEA SO RESEARCH ON AGING LA English DT Article C1 NIA,BEHAV & SOCIAL RES,BETHESDA,MD 20892. RUTGERS STATE UNIV,SOCIOL,NEW BRUNSWICK,NJ 08903. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0164-0275 J9 RES AGING JI Res. Aging PD DEC PY 1991 VL 13 IS 4 BP 458 EP 462 DI 10.1177/0164027591134003 PG 5 WC Gerontology SC Geriatrics & Gerontology GA GQ175 UT WOS:A1991GQ17500003 ER PT J AU GREENLEE, WF ANDERSEN, ME LUCIER, GW AF GREENLEE, WF ANDERSEN, ME LUCIER, GW TI A PERSPECTIVE ON BIOLOGICALLY-BASED APPROACHES TO DIOXIN RISK ASSESSMENT SO RISK ANALYSIS LA English DT Editorial Material ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MECHANISM; TOXICITY C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP GREENLEE, WF (reprint author), PURDUE UNIV,DEPT PHARMACOL & TOXICOL,W LAFAYETTE,IN 47906, USA. OI Andersen, Melvin/0000-0002-3894-4811 NR 19 TC 12 Z9 12 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1991 VL 11 IS 4 BP 565 EP 568 DI 10.1111/j.1539-6924.1991.tb00642.x PG 4 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA GV905 UT WOS:A1991GV90500001 PM 1720565 ER PT J AU REMMERS, EF SANO, H WILDER, RL AF REMMERS, EF SANO, H WILDER, RL TI PLATELET-DERIVED GROWTH-FACTORS AND HEPARIN-BINDING (FIBROBLAST) GROWTH-FACTORS IN THE SYNOVIAL TISSUE PATHOLOGY OF RHEUMATOID-ARTHRITIS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE RHEUMATOID ARTHRITIS; PLATELET-DERIVED GROWTH FACTOR; HEPARIN-BINDING (FIBROBLAST) GROWTH FACTOR; FIBROBLAST GROWTH FACTOR ID FACTOR A-CHAIN; SIGNAL TRANSDUCTION; FACTOR RECEPTORS; FACTOR-BETA; EXPRESSION; PDGF; INFLAMMATION; IDENTIFICATION; LOCALIZATION; SYNOVIOCYTES RP REMMERS, EF (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 10,RM 9N240,BETHESDA,MD 20892, USA. NR 51 TC 56 Z9 57 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 1991 VL 21 IS 3 BP 191 EP 199 DI 10.1016/0049-0172(91)90009-O PG 9 WC Rheumatology SC Rheumatology GA GW189 UT WOS:A1991GW18900009 PM 1724096 ER PT J AU GIFFORD, J SCANLEY, A AF GIFFORD, J SCANLEY, A TI STREAMLINING STATE AGENCY REQUIREMENTS FOR GRANTEE INSTITUTIONS SO SRA-JOURNAL OF THE SOCIETY OF RESEARCH ADMINISTRATORS LA English DT Article AB The Federal Demonstration Project (FDP) was established in 1988 to analyze the research administration system and recommend pilots to streamline and improve the management of research projects at three levels: federal, state, and institutional. A recent survey indicates there is much room for improvement in how state governments administer sponsored research in colleges and universities. It is time to look at research administration systems comprehensively-to target those requirements which are necessary, those which should be modified, and those which should be eliminated. Administrative flexibility is of greater strategic benefit to the state than achieving maximum reduction of risk through airtight administrative requirements. C1 NATL ACAD SCI,WASHINGTON,DC 20418. RP GIFFORD, J (reprint author), NIH,OFF EXTRAMURAL PROGRAMS,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOC RESEARCH ADMINISTRATORS PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036 SN 1062-8142 J9 SRA-J SOC RES ADMIN JI SRA-J. Soc. Res. Admin. PD WIN PY 1991 VL 23 IS 3 BP 27 EP 32 PG 6 WC Business; Management SC Business & Economics GA HE882 UT WOS:A1991HE88200007 ER PT J AU SIMON, R AF SIMON, R TI A DECADE OF PROGRESS IN STATISTICAL METHODOLOGY FOR CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Review AB Clinical trials played a dominant and expanding role in the evaluation of new treatments during the decade of the 1980s. There were major improvements in the quality of clinical trials in many medical fields. There were also important developments in the methodology of designing, monitoring, conducting, analysing, reporting and interpreting clinical trials. This paper attempts to review some of these developments. A comprehensive review is beyond the abilities of any one individual. Consequently, this paper attempts to offer a broad stroke description of this area and to highlight specific topics of importance based on my particular experience. An extensive, but non-comprehensive bibliography is included to provide entry points to the literature of methodologic developments for clinical trials in the 1980s. RP SIMON, R (reprint author), NCI,BLDG EPN,ROOM 739,BETHESDA,MD 20892, USA. NR 0 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC PY 1991 VL 10 IS 12 BP 1789 EP 1817 DI 10.1002/sim.4780101203 PG 29 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 HC150 UT WOS:A1991HC15000002 PM 1805314 ER PT J AU GAIL, MH AF GAIL, MH TI A BIBLIOGRAPHY AND COMMENTS ON THE USE OF STATISTICAL-MODELS IN EPIDEMIOLOGY IN THE 1980S SO STATISTICS IN MEDICINE LA English DT Review AB This paper reviews developments in statistical modelling in epidemiology in the 1980's, with emphasis on cohort and case-control studies. The central roles of the logistic and proportional hazard models are highlighted, and it is shown how these models lead to a deeper understanding of classical designs and methods of analysis as well as to efficient new designs and analytical procedures. The important area of model misspecification is discussed, including the problems of omitted latent structure, mis-modelling of available measurements, missing data and errors in measurements. Various designs motivated by the logistic model are illustrated numerically, and designs based on the proportional hazards model are discussed, as are papers on sample size determination. There are brief introductions to the literature on other topics, including attributable risk, disease clustering, family studies and genetics, analysis of disease incidence data, infectious disease, longitudinal data, screening and miscellaneous related topics in statistics. An extensive bibliography is indexed according to the outline of the paper. RP GAIL, MH (reprint author), NCI,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 0 TC 19 Z9 19 U1 0 U2 3 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 DEC PY 1991 VL 10 IS 12 BP 1819 EP 1885 DI 10.1002/sim.4780101204 PG 67 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 HC150 UT WOS:A1991HC15000003 PM 1805315 ER PT J AU DOHERTY, GM DOPPMAN, JL SHAWKER, TH MILLER, DL EASTMAN, RC GORDEN, P NORTON, JA AF DOHERTY, GM DOPPMAN, JL SHAWKER, TH MILLER, DL EASTMAN, RC GORDEN, P NORTON, JA TI RESULTS OF A PROSPECTIVE STRATEGY TO DIAGNOSE, LOCALIZE, AND RESECT INSULINOMAS SO SURGERY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 14-16, 1991 CL SAN JOSE, CA SP AMER ASSOC ENDOCRINE SURGEONS ID OCCULT INSULINOMAS AB Since 1982, 25 consecutive patients with benign sporadic (non-multiple endocrine neoplasia type I) insulinomas have been studied. Most were referred because either the tumor was not identified at the referring institution or the diagnosis was unclear. Each patient suffered severe neuroglycopenic symptoms for a median of 24 months before diagnosis of insulinoma, and 32% had hypoglycemic seizures. Eighteen patients (72%) had a confirmed weight gain. Each patient underwent a supervised fast until 72 hours or the onset of significant neuroglycopenic symptoms (median duration 16 hours), with serum levels of glucose (median 35 mg/dl; range 24 to 46 mg/dl), insulin (median 21-mu-U/ml; range 11 to 230-mu-U/ml), C-peptide (median 2.5 ng/ml; range 1.0 to 7.2 ng/ml), and proinsulin fraction (median 55%; range 14% to 86%) measured at the termination of the fast. Preoperative imaging with ultrasonography, computed tomography, magnetic resonance, and angiography visualized tumor in a minority of patients (26%, 17%, 25%, and 35%, respectively); in 48% of patients one or more imaging study results was positive. Selective portal venous sampling for insulin was the most informative localizing test (77% positive; no false-positive results). Tumor was resected for cure in 24 of 25 patients. Intraoperative ultrasonography identified nonpalpable tumor in seven patients and was crucial to the achievement of this high rate of surgical cure. We conclude that the diagnosis of insulinoma can be made by the results of a supervised fast, portal venous sampling is the most sensitive preoperative test for localizing insulinomas, and intraoperative ultrasonography is essential for intraoperative detection of insulinomas. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. NIDDKD,DIABET BRANCH,BETHESDA,MD. NR 14 TC 132 Z9 142 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1991 VL 110 IS 6 BP 989 EP 997 PG 9 WC Surgery SC Surgery GA GU130 UT WOS:A1991GU13000010 PM 1745987 ER PT J AU THOM, AK NORTON, JA AXIOTIS, CA JENSEN, RT AF THOM, AK NORTON, JA AXIOTIS, CA JENSEN, RT TI LOCATION, INCIDENCE, AND MALIGNANT POTENTIAL OF DUODENAL GASTRINOMAS SO SURGERY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 14-16, 1991 CL SAN JOSE, CA SP AMER ASSOC ENDOCRINE SURGEONS ID ZOLLINGER-ELLISON SYNDROME; SURGICAL-MANAGEMENT; TUMORS AB Duodenal gastrinomas are increasingly found at surgery, yet information about their location and characteristics is based on the results of either pooled series or retrospective reviews of small numbers of selected cases. To address these issues we have analyzed the location, incidence, and malignant potential of duodenal gastrinomas in 65 consecutive patients who underwent removal of all tumor as part of a 10-year prospective study to resect gastrinomas in patients with sporadic Zollinger-Ellison syndrome. The primary gastrinoma was located in the duodenum in 24 patients (37%). There were 19 men and five women aged 32 to 69 years (mean 49.4 years), with symptoms for 0.6 to 35 years (mean 7.9 years). Preoperative studies included serum gastrin levels of 114 to 35,798 pg/ml (mean 2060 pg/ml), basal acid output of 7 to 95 mEq/hr (mean 37.6 mEq/hr), and a positive secretin test result in 22 patients. Preoperative imaging studies identified tumor in the duodenal area in 11 patients (46%), but most positive imaging findings were metastatic gastrinoma in lymph nodes, and the primary duodenal tumor itself was identified in only two patients. Portal venous sampling had a localizing gastrin gradient in the inferior or superior pancreaticoduodenal vein in 17 of 23 patients (74%). Each of the 24 patients had a single, small duodenal wall tumor of 2.8 to 10.1 mm diameter (mean 6 mm). Each tumor stained positive for gastrin by immunohistochemistry. Seventeen tumors (71%) were located in the first portion of the duodenum, five (21%) in the second, and two (8%) in the third. Each tumor originated in the submucosa, and 13 (54%) were limited to the submucosa, whereas 11 (46%) were locally invasive, four (16%) extending into the muscularis mucosa and seven (29%) into the muscularis propria. Thirteen patients (54%) had spread to regional lymph nodes, whereas two (8%) had liver metastases. Lymph node metastases were seen with larger duodenal tumors (mean 7.1 vs 5.4 mm; p < 0.01). The data suggest that a single duodenal wall gastrinoma is a common cause of Zollinger-Ellison syndrome (37%). These small (< 1 cm) tumors are located in the submucosal layer of the proximal duodenum (92%) and are malignant more often than previously thought (54%). C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NCI,OFF DIRECTOR,WARREN GRANT MAGNUSON,CLIN CTR,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD. NR 18 TC 91 Z9 93 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1991 VL 110 IS 6 BP 1086 EP 1093 PG 8 WC Surgery SC Surgery GA GU130 UT WOS:A1991GU13000023 PM 1745977 ER PT J AU ZEIGER, MA NIEMAN, LK CUTLER, GB CHROUSOS, GP DOPPMAN, JL TRAVIS, WD NORTON, JA AF ZEIGER, MA NIEMAN, LK CUTLER, GB CHROUSOS, GP DOPPMAN, JL TRAVIS, WD NORTON, JA TI PRIMARY BILATERAL ADRENOCORTICAL CAUSES OF CUSHINGS-SYNDROME SO SURGERY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 14-16, 1991 CL SAN JOSE, CA SP AMER ASSOC ENDOCRINE SURGEONS ID MACRONODULAR ADRENAL-HYPERPLASIA; STIMULATION TEST; DISEASE; DIAGNOSIS AB Nontumorous primary adrenal causes of Cushing's syndrome are exceedingly rare. Herein we review our results with seven patients in whom there is biochemical evidence of a primary (adrenocorticotropin independent) bilateral adrenal cause of endogenous hypercortisolism. Each patient had low plasma adrenocorticotropin levels. All patients had elevated 24-hour urinary free cortisol levels and 17-hydroxycorticosteroids that were not suppressed by high-dose dexamethasone. Plasma levels of adrenocorticotropin and cortisol were not elevated by ovine corticotropin-releasing factor. No patient had a gradient between petrosal and peripheral adrenocorticotropin levels. No pituitary tumors were detected by magnetic resonance imaging or computed tomography. Five of six patients who underwent iodocholesterol scanning showed bilateral adrenal activity. Computed tomographic and magnetic resonance imaging of the abdomen demonstrated bilateral small adrenal glands in three patients, an adrenal mass in one patient with Carney's complex, and massively enlarged glands in three patients. Each patient underwent bilateral adrenalectomy and was given glucocorticoid and mineralocorticoid replacement. Pathologic examination of four of these bilateral adrenal specimens revealed primary pigmented micronodular adrenocortical disease, with adrenal gland weights between 2.5 and 13.4 gm (mean 5.2 gm). However, the remaining three patients had primary adrenocorticotropin-independent bilateral macronodular adrenocortical disease with adrenal gland weights between 32 and 81 gm (mean 52 gm). Although each of the patients with primary pigmented micronodular adrenocortical disease was cured by bilateral adrenalectomy through a posterior approach, two of the three patients required an anterior approach. We conclude that Cushing's syndrome can arise through two distinct forms of primary bilateral adrenal cortical disease. Computed tomography is important in evaluation of these patients because the size of the adrenal glands influences the surgical approach. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 22 TC 37 Z9 38 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1991 VL 110 IS 6 BP 1106 EP 1115 PG 10 WC Surgery SC Surgery GA GU130 UT WOS:A1991GU13000026 PM 1745978 ER PT J AU UDELSMAN, R BLAKE, MJ HOLBROOK, NJ AF UDELSMAN, R BLAKE, MJ HOLBROOK, NJ TI MOLECULAR RESPONSE TO SURGICAL STRESS - SPECIFIC AND SIMULTANEOUS HEAT-SHOCK PROTEIN INDUCTION IN THE ADRENAL-CORTEX, AORTA, AND VENA-CAVA SO SURGERY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 14-16, 1991 CL SAN JOSE, CA SP AMER ASSOC ENDOCRINE SURGEONS ID EXPRESSION; SYSTEM; CELLS AB The endocrine response to surgical stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Potential interactions between endocrine and cellular stress responses have not been investigated in vivo. A surgical model was developed to define the genetic response to surgical stress. Wistar rats underwent ether anesthesia, laparotomy, hemorrhage, and variable recovery periods. Tissues were subsequently harvested and the RNA was isolated and probed for HSP70 messenger RNA levels. These studies showed a strong induction of HSP70 but only in the adrenal gland, aorta, and vena cava. This specific induction was rapid, occurring 30 minutes after surgery, and dramatic (greater than twentyfold induction). The induction occurred in parallel with HPA axis activation and was adrenal cortical specific as determined by in situ hybridization. These observations suggest a functional interaction between the molecular stress response and HPA axis activation. C1 NIA,GERONTOL RES CTR,MOLEC GENET LAB,BALTIMORE,MD 21224. RP UDELSMAN, R (reprint author), JOHNS HOPKINS UNIV HOSP,DEPT SURG,DIV ONCOL & ENDOCRINE SURG,HARVEY 808,600 N WOLFE ST,BALTIMORE,MD 21218, USA. NR 23 TC 66 Z9 66 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1991 VL 110 IS 6 BP 1125 EP 1131 PG 7 WC Surgery SC Surgery GA GU130 UT WOS:A1991GU13000028 PM 1660628 ER PT J AU CLARK, GC TAYLOR, MJ TRITSCHER, AM LUCIER, GW AF CLARK, GC TAYLOR, MJ TRITSCHER, AM LUCIER, GW TI TUMOR-NECROSIS-FACTOR INVOLVEMENT IN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN-MEDIATED ENDOTOXIN HYPERSENSITIVITY IN C57BL/6J MICE CONGENIC AT THE AH LOCUS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID LIPOPROTEIN-LIPASE ACTIVITY; FACTOR-ALPHA; TOXICITY; CACHECTIN; "2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; EXPOSURE; INTERLEUKIN-1; SUPPRESSION; MECHANISMS; RESISTANCE RP CLARK, GC (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,MD D404,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 83 Z9 84 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1991 VL 111 IS 3 BP 422 EP 431 DI 10.1016/0041-008X(91)90247-C PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GV173 UT WOS:A1991GV17300004 PM 1660630 ER PT J AU CHEN, GJ PILLAI, R ERICKSON, JR MARTINEZ, F ESTRADA, AL WATSON, RR AF CHEN, GJ PILLAI, R ERICKSON, JR MARTINEZ, F ESTRADA, AL WATSON, RR TI COCAINE IMMUNOTOXICITY - ABNORMAL CYTOKINE PRODUCTION IN HISPANIC DRUG-USERS SO TOXICOLOGY LETTERS LA English DT Article DE INTERLEUKIN-1; INTERLEUKIN-2; GAMMA-INTERFERON; SOLUBLE INTERLEUKIN-2 RECEPTOR; IMMUNODEFICIENCY ID ABUSE; MOUSE AB Peripheral blood lymphocytes from 47 Hispanic poly-drug users with a history of cocaine abuse were analyzed for in vitro production of interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-interferon (IFN) and plasma levels of soluble IL-2 receptor (SIL-2R). Cocaine use was confirmed and quantified by analysis of hair and urine samples, and subjects were grouped into 3 based on the extent of cocaine metabolites detected. No significant differences in IL-1 and IFN production were seen between the 3 groups. However, subjects with higher levels of cocaine in hair also showed higher levels of IL-2. In addition, a positive correlation was seen between cocaine concentrations and IL-2 levels. A corresponding negative correlation was seen between cocaine levels and levels of plasma SIL-2R. These findings suggest modulation of the IL-2 network by cocaine in poly-drug users. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT FAMILY & COMMUNITY MED,NIAAA,SPECIALIZED ALCOHOL RES CTR,TUCSON,AZ 85724. FU NIAAA NIH HHS [AA08037]; NIDA NIH HHS [DA 04827, R18 DA 05748] NR 18 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1991 VL 59 IS 1-3 BP 81 EP 88 PG 8 WC Toxicology SC Toxicology GA GW207 UT WOS:A1991GW20700008 PM 1721732 ER PT J AU ZETTERGREN, LD CONRAD, CA PETERING, DH WEBER, DN GOODRICH, MS AF ZETTERGREN, LD CONRAD, CA PETERING, DH WEBER, DN GOODRICH, MS TI IMMUNOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDIES OF CADMIUM ASSOCIATED PROTEINS IN RANA TADPOLES SO TOXICOLOGY LETTERS LA English DT Article DE CADMIUM; METALLOTHIONEIN; PHYLOGENETIC; IMMUNOHISTOCHEMICAL; DEVELOPMENTAL EFFECTS ID METALLOTHIONEIN; ANTIBODY; RAT; ONTOGENY; PIPIENS; FROG AB Previous observations suggested that Rana tadpoles treated with aqueous cadmium (Cd) accumulate Cd in their liver and mesonephros. In order to study the response to Cd in these tissues we (a) exposed tadpoles in mid-limb bud stages to sublethal quantities of Cd, (b) isolated Cd-associated protein (CAP) from a liver cytosol fraction, (c) prepared a heterologous rabbit antiserum against glutaraldehyde-treated CAP (G-CAP), (d) used the rabbit anti-G-CAP antiserum in order to assess the tissue distribution of CAP in Cd-treated and untreated tadpoles, and (e) assessed species crossreactivities of our anti-G-CAP with CAPs and metallothioneins (MTs) isolated from Cd-treated vertebrate liver cytosol fractions. We found that (a) CAP was present in higher quantities in liver cytosol obtained from Cd-treated tadpoles compared to liver cytosol obtained from untreated control tadpoles, (b) indirect immunofluorescent analysis revealed that CAP was localized in liver hepatocytes and kidney tubule epithelial cells in Cd-treated tadpoles, and (c) the anti-G-CAP crossreacted with rodent and fish CAP. These observations suggest that the developing liver and mesonephros are involved in responses to toxic metals and that our anti G-CAP antiserum may be used to gauge exposure to environment Cd. C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53201. NIEHS,CTR MARINE & FRESHWATER BIOMED CORE,GREAT LAKES RES FACIL,MILWAUKEE,WI. RP ZETTERGREN, LD (reprint author), CARROLL COLL,DEPT BIOL,WAUKESHA,WI 53186, USA. FU NIEHS NIH HHS [ES 04184] NR 27 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1991 VL 59 IS 1-3 BP 221 EP 228 DI 10.1016/0378-4274(91)90075-H PG 8 WC Toxicology SC Toxicology GA GW207 UT WOS:A1991GW20700025 PM 1755029 ER PT J AU ROSENGARD, BR KORTZ, EO OJIKUTU, CA GUZZETTA, PC SUNDT, TM SMITH, CV NAKAJIMA, K BOORSTEIN, SM HILL, GS SACHS, DH AF ROSENGARD, BR KORTZ, EO OJIKUTU, CA GUZZETTA, PC SUNDT, TM SMITH, CV NAKAJIMA, K BOORSTEIN, SM HILL, GS SACHS, DH TI THE FAILURE OF SKIN-GRAFTING TO BREAK TOLERANCE TO CLASS-I-DISPARATE RENAL-ALLOGRAFTS IN MINIATURE SWINE DESPITE INDUCING MARKED ANTIDONOR CELLULAR-IMMUNITY SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; REJECTION INVIVO; CYCLOSPORINE-A; T-CELLS; TRANSPLANTATION; SURVIVAL; ANTIGEN; INVITRO; RAT; RESPONSES AB Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLA(ad) and SLA(dd) hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLA(ad) animal and an immunized SLA(dd) animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. NR 31 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC PY 1991 VL 52 IS 6 BP 1044 EP 1052 DI 10.1097/00007890-199112000-00020 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV969 UT WOS:A1991GV96900020 PM 1750067 ER PT J AU HOHMAN, RJ HULTSCH, T AF HOHMAN, RJ HULTSCH, T TI IMMUNOSUPPRESSIVE DRUGS REVEAL SIMILARITIES BETWEEN IGE RECEPTOR AND T-CELL RECEPTOR SIGNALING PATHWAYS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT INTERNATIONAL CONGRESS ON FK 506 CY AUG 21-24, 1991 CL UNIV PITTSBURGH, PITTSBURGH, PA SP FUJISAWA PHARM HO UNIV PITTSBURGH ID HIGH-AFFINITY; MAST-CELLS; TRANSFECTED CELLS; IMMUNOGLOBULIN-E; IMMUNOPHILIN; EXPRESSION; BASOPHILS; RELEASE; BINDING RP HOHMAN, RJ (reprint author), NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C215,BETHESDA,MD 20892, USA. NR 19 TC 2 Z9 3 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1991 VL 23 IS 6 BP 2907 EP 2911 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV175 UT WOS:A1991GV17500058 PM 1836288 ER PT J AU FUKUZAWA, M OKADA, A SHEARER, GM AF FUKUZAWA, M OKADA, A SHEARER, GM TI EFFECT OF FK-506 ON CD-4+ AND CD-8+ T-CELL FUNCTION INVIVO SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT INTERNATIONAL CONGRESS ON FK 506 CY AUG 21-24, 1991 CL UNIV PITTSBURGH, PITTSBURGH, PA SP FUJISAWA PHARM HO UNIV PITTSBURGH ID CYCLOSPORINE-A; INVITRO; STREPTOMYCES; FK506; IMMUNITY C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP FUKUZAWA, M (reprint author), OSAKA UNIV,SCH MED,DEPT PEDIAT SURG,1-1-50 FUKUSHIMA,FUKUSHIMA KU,OSAKA 553,JAPAN. NR 13 TC 7 Z9 7 U1 0 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1991 VL 23 IS 6 BP 2945 EP 2947 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV175 UT WOS:A1991GV17500071 PM 1721321 ER PT J AU HULTSCH, T HOHMAN, RJ AF HULTSCH, T HOHMAN, RJ TI CATEGORIZING RECEPTOR-SIGNALING PATHWAYS WITH FK-506 AND RAPAMYCIN SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT INTERNATIONAL CONGRESS ON FK 506 CY AUG 21-24, 1991 CL UNIV PITTSBURGH, PITTSBURGH, PA SP FUJISAWA PHARM HO UNIV PITTSBURGH ID GENE-EXPRESSION; LYMPHOCYTES-T; MAST-CELLS; INTERLEUKIN-3; CYCLOSPORINE; ACTIVATION; FK506; IGE RP HULTSCH, T (reprint author), NIH,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C215,BETHESDA,MD 20892, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1991 VL 23 IS 6 BP 2961 EP 2963 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV175 UT WOS:A1991GV17500078 PM 1721328 ER PT J AU CARROLL, PB CAOHUY, H LEE, G DELAFUENTE, M POLLARD, HB ATWATER, I AF CARROLL, PB CAOHUY, H LEE, G DELAFUENTE, M POLLARD, HB ATWATER, I TI SYNEXIN - A TARGET PROTEIN FOR TOXIC EFFECTS OF CYCLOSPORINE AND FK-506 IN ENDOCRINE-CELLS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT INTERNATIONAL CONGRESS ON FK 506 CY AUG 21-24, 1991 CL UNIV PITTSBURGH, PITTSBURGH, PA SP FUJISAWA PHARM HO UNIV PITTSBURGH ID MEMBRANE-FUSION; RAT ISLETS; INHIBITION C1 NIH,NIDDK,CELL BIOL & GENET LAB,BLDG 8,ROOM 403,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,DEPT MED,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA 15261. RP POLLARD, HB (reprint author), NIH,NIDDK,CELL BIOL & GENET LAB,BLDG 8,ROOM 403,BETHESDA,MD 20892, USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1991 VL 23 IS 6 BP 3166 EP 3168 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV175 UT WOS:A1991GV17500146 PM 1721394 ER PT J AU FUJINO, Y CHAN, CC DESMET, MD HIKITA, N GERY, I MOCHIZUKI, M NUSSENBLATT, RB AF FUJINO, Y CHAN, CC DESMET, MD HIKITA, N GERY, I MOCHIZUKI, M NUSSENBLATT, RB TI FK-506 TREATMENT OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN PRIMATES SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT INTERNATIONAL CONGRESS ON FK 506 CY AUG 21-24, 1991 CL UNIV PITTSBURGH, PITTSBURGH, PA SP FUJISAWA PHARM HO UNIV PITTSBURGH ID IMMUNOSUPPRESSIVE AGENT; FK506; INVITRO; UVEITIS; RATS; CYCLOSPORINE; DISEASE; ANTIGEN; CANINE C1 NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892. KURUME UNIV,DEPT OPHTHALMOL,KURUME,FUKUOKA 830,JAPAN. RP NUSSENBLATT, RB (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 27 TC 5 Z9 5 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1991 VL 23 IS 6 BP 3335 EP 3338 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GV175 UT WOS:A1991GV17500210 PM 1721454 ER PT J AU MINK, MA STEC, DS COLLINS, PL AF MINK, MA STEC, DS COLLINS, PL TI NUCLEOTIDE-SEQUENCES OF THE 3'LEADER AND 5'TRAILER REGIONS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS GENOMIC RNA SO VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; NEWCASTLE-DISEASE VIRUS; MESSENGER-RNAS; L-PROTEIN; INTERGENIC SEQUENCES; MOLECULAR-CLONING; RABIES GENOME; MUMPS-VIRUS; GENE ORDER; NP PROTEIN C1 NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892. NR 44 TC 53 Z9 57 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1991 VL 185 IS 2 BP 615 EP 624 DI 10.1016/0042-6822(91)90532-G PG 10 WC Virology SC Virology GA GR867 UT WOS:A1991GR86700011 PM 1840712 ER PT J AU PEDEN, K EMERMAN, M MONTAGNIER, L AF PEDEN, K EMERMAN, M MONTAGNIER, L TI CHANGES IN GROWTH-PROPERTIES ON PASSAGE IN TISSUE-CULTURE OF VIRUSES DERIVED FROM INFECTIOUS MOLECULAR CLONES OF HIV-1LAI, HIV-1MAL, AND HIV-1ELI SO VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS-ASSOCIATED RETROVIRUS; NUCLEOTIDE-SEQUENCE; TYPE-1 GP120; HTLV-III; T-CELLS; CLONING; DNA; EXPRESSION; CAPACITY C1 INST PASTEUR,UNITE ONCOL VIRALE,F-75724 PARIS 15,FRANCE. RP PEDEN, K (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,ROOM 310,BETHESDA,MD 20892, USA. FU NIMHD NIH HHS [MD800803] NR 42 TC 300 Z9 302 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1991 VL 185 IS 2 BP 661 EP 672 DI 10.1016/0042-6822(91)90537-L PG 12 WC Virology SC Virology GA GR867 UT WOS:A1991GR86700016 PM 1683726 ER PT J AU NISHIKAWA, K HOSHINO, Y GORZIGLIA, M AF NISHIKAWA, K HOSHINO, Y GORZIGLIA, M TI SEQUENCE OF THE VP7 GENE OF CHICKEN ROTAVIRUS CH2 STRAIN OF SEROTYPE-7 ROTAVIRUS SO VIROLOGY LA English DT Note ID NUCLEOTIDE-SEQUENCE; NEUTRALIZATION EPITOPES; MONOCLONAL-ANTIBODIES; HOMOLOGOUS GENES; GLYCOPROTEIN VP7; ACID; IDENTIFICATION; PROTEIN; ANTIGEN; REGION C1 NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892. NR 30 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1991 VL 185 IS 2 BP 853 EP 856 DI 10.1016/0042-6822(91)90558-S PG 4 WC Virology SC Virology GA GR867 UT WOS:A1991GR86700037 PM 1660203 ER PT J AU TOYAMA, R GOLDSTEIN, DJ SCHLEGEL, R DHAR, R AF TOYAMA, R GOLDSTEIN, DJ SCHLEGEL, R DHAR, R TI A GENOMIC SEQUENCE OF THE SCHIZOSACCHAROMYCES-POMBE 16 KDA VACUOLAR H+-ATPASE SO YEAST LA English DT Note DE SEQUENCE; S-POMBE; VACUOLAR H+-ATPASE ID EVOLUTION; CDNA AB We have isolated the gene encoding the 16 kDa vacuolar H+-ATPase from Schizosaccharomyces pombe. On the basis of RNA splicing signals and amino acid sequence homology with other 16 kDa H+-ATPases, the genomic DNA sequence indicated the 16 kDa protein is encoded by five exons. The C-terminal 50 amino acids has more than 90% homology with vacuolar H+-ATPases of mammalian cells. C1 NCI,MOLEC VIROL LAB,BLDG 41,ROOM B506,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT PATHOL,WASHINGTON,DC 20007. NR 8 TC 10 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD DEC PY 1991 VL 7 IS 9 BP 989 EP 991 DI 10.1002/yea.320070911 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA HB155 UT WOS:A1991HB15500010 PM 1839480 ER PT J AU LEE, FJS MOSS, J AF LEE, FJS MOSS, J TI CLONING OF A SACCHAROMYCES-CEREVISIAE GENE ENCODING A PROTEIN HOMOLOGOUS TO ALLANTOICASE OF NEUROSPORA-CRASSA SO YEAST LA English DT Note DE SACCHAROMYCES-CEREVISIAE; CHROMOSOME-III; ALLANTOICASE; PURINE CATABOLISM ID ELEMENTS RP LEE, FJS (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 3 TC 8 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD DEC PY 1991 VL 7 IS 9 BP 993 EP 995 DI 10.1002/yea.320070912 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA HB155 UT WOS:A1991HB15500011 PM 1839481 ER PT J AU AMAGAI, M KLAUSKOVTUN, V STANLEY, JR AF AMAGAI, M KLAUSKOVTUN, V STANLEY, JR TI AUTOANTIBODIES AGAINST A NOVEL EPITHELIAL CADHERIN IN PEMPHIGUS-VULGARIS, A DISEASE OF CELL-ADHESION SO CELL LA English DT Article ID NORMAL HUMAN-SKIN; FOLIACEUS AUTOANTIBODIES; DESMOSOMAL GLYCOPROTEIN; PLASMINOGEN-ACTIVATOR; MOLECULE UVOMORULIN; CYTOPLASMIC DOMAIN; PLACENTAL CADHERIN; SEQUENCE-ANALYSIS; PASSIVE TRANSFER; GENE FAMILY AB Pemphigus vulgaris (PV) is a life-threatening skin disease in which autoantibodies against a keratinocyte cell surface 130 kd glycoprotein, PV antigen (PVA), cause loss of cell-cell adhesion, with resultant epidermal blisters. We used affinity-purified PV IgG to isolate CDNA, containing the entire coding sequence for PVA, from human keratinocyte expression libraries. Northern blot analysis indicated PV mRNA expression only in stratified squamous epithelia. The deduced amino acid sequence of PVA was unique but showed significant homology with members of the cadherin family of Ca2+-dependent cell adhesion molecules, most markedly to desmoglein I. These findings demonstrate that a novel epithelial cadherin is the target of autoantibodies in PV. RP AMAGAI, M (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 71 TC 665 Z9 686 U1 9 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 29 PY 1991 VL 67 IS 5 BP 869 EP 877 DI 10.1016/0092-8674(91)90360-B PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GT755 UT WOS:A1991GT75500006 PM 1720352 ER PT J AU MILLER, EK LI, L DESIMONE, R AF MILLER, EK LI, L DESIMONE, R TI A NEURAL MECHANISM FOR WORKING AND RECOGNITION MEMORY IN INFERIOR TEMPORAL CORTEX SO SCIENCE LA English DT Article ID STATE DEPENDENT ACTIVITY; MONKEY VISUAL-CORTEX; SHORT-TERM; RESPONSES; NEURONS; TASKS; V4 AB Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurrently viewing other items. The neuronal response to an incoming visual stimulus was attenuated if it matched a stimulus actively held in working memory, even when several other stimuli intervened. The neuronal response to novel stimuli declined as the stimuli became familiar to the animal. IT neurons appear to function as adaptive mnemonic "filters" that preferentially pass information about new, unexpected, or not recently seen stimuli. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 18 TC 434 Z9 441 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 29 PY 1991 VL 254 IS 5036 BP 1377 EP 1379 DI 10.1126/science.1962197 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GR777 UT WOS:A1991GR77700056 PM 1962197 ER PT J AU CHAN, AML RUBIN, JS BOTTARO, DP HIRSCHFIELD, DW CHEDID, M AARONSON, SA AF CHAN, AML RUBIN, JS BOTTARO, DP HIRSCHFIELD, DW CHEDID, M AARONSON, SA TI IDENTIFICATION OF A COMPETITIVE HGF ANTAGONIST ENCODED BY AN ALTERNATIVE TRANSCRIPT SO SCIENCE LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; HEPATOCYTE GROWTH-FACTOR; MOLECULAR-CLONING; EPITHELIAL-CELLS; BIOLOGICAL CHARACTERIZATION; SCATTER FACTOR; PURIFICATION; EXPRESSION; PROTEIN; CDNA AB We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c-met proto-oncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 37 TC 194 Z9 196 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 29 PY 1991 VL 254 IS 5036 BP 1382 EP 1385 DI 10.1126/science.1720571 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GR777 UT WOS:A1991GR77700058 PM 1720571 ER PT J AU HART, MJ EVA, A EVANS, T AARONSON, SA CERIONE, RA AF HART, MJ EVA, A EVANS, T AARONSON, SA CERIONE, RA TI CATALYSIS OF GUANINE-NUCLEOTIDE EXCHANGE ON THE CDC42HS PROTEIN BY THE DBL ONCOGENE PRODUCT SO NATURE LA English DT Article ID GTP-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; CELL POLARITY; HUMAN HOMOLOG; GENE; PURIFICATION; CYCLE; G25K; IDENTIFICATION AB THE superfamily of low molecular mass GTP-binding proteins, for which the ras proteins are prototypes, has been implicated in the regulation of diverse biological activities including protein trafficking, secretion, and cell growth and differentiation 1-3. One member of this family, CDC42Hs (originally referred to as Gp or G25K) 4-5, seems to be the human homologue of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc (refs 6-9). A second S. cerevisiae protein, CDC24 (ref. 10), which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonrandom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product 11-14. Here we show that dbl specifically catalyses the dissociation of GDP from CDC42Hs and thereby qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. Although guanine nucleotide exchange activities have been previously described for other members of the Ras-related GTP-binding protein family 15-17, this is the first demonstration, to our knowledge, of the involvement of a human oncogenic protein in catalysing exchange activity. C1 CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. GENENTECH INC,DEPT CELL BIOL,S SAN FRANCISCO,CA 94080. RP HART, MJ (reprint author), CORNELL UNIV,DEPT BIOCHEM CELLULAR & MOLEC BIOL,ITHACA,NY 14853, USA. RI Eva, Alessandra/J-8268-2016 OI Eva, Alessandra/0000-0003-2949-078X NR 22 TC 367 Z9 370 U1 1 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 28 PY 1991 VL 354 IS 6351 BP 311 EP 314 DI 10.1038/354311a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT204 UT WOS:A1991GT20400049 PM 1956381 ER PT J AU FALLOON, J KOVACS, J HUGHES, W ONEILL, D POLIS, M DAVEY, RT ROGERS, M LAFON, S FEUERSTEIN, I LANCASTER, D LAND, M TUAZON, C DOHN, M GREENBERG, S LANE, HC MASUR, H AF FALLOON, J KOVACS, J HUGHES, W ONEILL, D POLIS, M DAVEY, RT ROGERS, M LAFON, S FEUERSTEIN, I LANCASTER, D LAND, M TUAZON, C DOHN, M GREENBERG, S LANE, HC MASUR, H TI A PRELIMINARY EVALUATION OF 566C80 FOR THE TREATMENT OF PNEUMOCYSTIS PNEUMONIA IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HYDROXYNAPHTHOQUINONE; POTENT AB Background. The drug 566C80 is an investigational hydroxynaphthoquinone that is active against Pneumocystis carinii in vitro and in animal models. Initial studies in humans indicate that 566C80 is safe and has adequate bioavailability after oral administration. Methods. We conducted an open-label trial of 566C80 in 34 adults with the acquired immunodeficiency syndrome (AIDS) and untreated pneumocystis pneumonia. All the patients had a partial pressure of arterial oxygen of at least 60 mm Hg while breathing room air. They were enrolled sequentially in three cohorts taking 566C80 at different dosages, all administered orally: 750 mg three times daily for 5 days, then twice daily for 16 days; 750 mg three times daily for 21 days; and 750 mg four times daily for 21 days. Results. All 34 patients survived, and 27 (79 percent) were successfully treated with 566C80 alone. The mean partial pressure of oxygen in 33 patients was 78 mm Hg at entry and 93 mm Hg after the course of 566C80 (P < 0.001). In five patients (15 percent) the drug was discontinued because of lack of response. In four patients (12 percent), the drug was discontinued because of toxicity (fever and rash in two patients each). In two of these, treatment was considered to have succeeded because 566C80 was not discontinued because of toxicity until after day 14. Five of the successfully treated patients had rashes that resolved despite continued therapy. In nine patients, serum alanine aminotransferase levels rose above 100 U per liter. During the first three months after the completion of therapy, pneumocystis pneumonia recurred in 4 of the 27 successfully treated patients, and another 3 patients had recurrences between month 3 and month 6 of follow-up. The mean (+/- SEM) steady-state plasma levels of 566C80 were similar in the three cohorts: 16.3 +/- 2.10, 20.4 +/- 2.48, and 18.9 +/- 3.08-mu-g per milliliter in the patients taking the drug twice daily, three times daily, and four times daily, respectively. Conclusions. From these preliminary data, the investigational compound 566C80 appears to be a safe, effective, and well-tolerated therapy for P. carinii pneumonia of mild-to-moderate severity in patients with AIDS. C1 WARREN G MAGNUSON CLIN CTR, DEPT RADIOL, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. BURROUGHS WELLCOME CO, RES TRIANGLE PK, NC 27709 USA. GEORGE WASHINGTON UNIV, MED CTR, WASHINGTON, DC 20037 USA. REG MED CTR, MEMPHIS, TN USA. BAPTIST MEM HOSP, MEMPHIS, TN 38146 USA. UNIV CINCINNATI, CINCINNATI, OH 45221 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. RP FALLOON, J (reprint author), WARREN G MAGNUSON CLIN CTR, DEPT CRIT CARE MED, BLDG 10, RM 7D43, BETHESDA, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 10 TC 78 Z9 78 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 1991 VL 325 IS 22 BP 1534 EP 1538 DI 10.1056/NEJM199111283252202 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GR380 UT WOS:A1991GR38000002 PM 1944437 ER PT J AU ELDRIDGE, R PARRY, DM AF ELDRIDGE, R PARRY, DM TI BRAIN-TUMORS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID NEUROFIBROMATOSIS C1 NCI, BETHESDA, MD 20892 USA. RP ELDRIDGE, R (reprint author), NINCDS, BETHESDA, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 1991 VL 325 IS 22 BP 1584 EP 1584 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GR380 UT WOS:A1991GR38000024 ER PT J AU THORNTONMANNING, JR RUANGYUTTIKARN, W GONZALEZ, FJ YOST, GS AF THORNTONMANNING, JR RUANGYUTTIKARN, W GONZALEZ, FJ YOST, GS TI METABOLIC-ACTIVATION OF THE PNEUMOTOXIN, 3-METHYLINDOLE, BY VACCINIA-EXPRESSED CYTOCHROME-P450S SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CDNA-DIRECTED EXPRESSION; HUMAN-LIVER; PULMONARY-EDEMA; RABBIT LUNG; SEQUENCE; RAT; IDENTIFICATION; INDUCTION; GENE; CELLS C1 UNIV UTAH,DEPT PHARMACOL & TOXICOL,112 SKAGGS HALL,SALT LAKE CITY,UT 84112. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL02119, HL13645] NR 44 TC 41 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 27 PY 1991 VL 181 IS 1 BP 100 EP 107 DI 10.1016/S0006-291X(05)81387-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GR961 UT WOS:A1991GR96100015 PM 1958177 ER PT J AU HU, ZZ DUFAU, ML AF HU, ZZ DUFAU, ML TI MULTIPLE AND DIFFERENTIAL REGULATION OF OVARIAN PROLACTIN RECEPTOR MESSENGER-RNAS AND THEIR EXPRESSION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT OVARY; PURIFICATION; CELL C1 NICHHD,MOLEC ENDOCRINOL SECT,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 14 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 27 PY 1991 VL 181 IS 1 BP 219 EP 225 DI 10.1016/S0006-291X(05)81405-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GR961 UT WOS:A1991GR96100033 PM 1958189 ER PT J AU GIRI, PR HIGUCHI, S KINCAID, RL AF GIRI, PR HIGUCHI, S KINCAID, RL TI CHROMOSOMAL MAPPING OF THE HUMAN GENES FOR THE CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE (CALCINEURIN) CATALYTIC SUBUNIT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BINDING-PROTEIN; IDENTIFICATION; CLONING; DOMAIN RP GIRI, PR (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,ROCKVILLE,MD 20852, USA. NR 21 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 27 PY 1991 VL 181 IS 1 BP 252 EP 258 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GR961 UT WOS:A1991GR96100038 PM 1659808 ER PT J AU STAMLER, J BERGE, KG DAVIS, BR HADLEY, E PRESSEL, S PROBSTFIELD, J AF STAMLER, J BERGE, KG DAVIS, BR HADLEY, E PRESSEL, S PROBSTFIELD, J TI PREVENTION OF STROKE IN OLDER PERSONS WITH ISOLATED SYSTOLIC HYPERTENSION - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP STAMLER, J (reprint author), NIH,SYSTOL HYPERTENS ELDERLY PROGRAM RES GRP,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 27 PY 1991 VL 266 IS 20 BP 2829 EP 2830 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GQ722 UT WOS:A1991GQ72200011 ER PT J AU SLOAND, EM PITT, E CHIARELLO, RJ NEMO, GJ AF SLOAND, EM PITT, E CHIARELLO, RJ NEMO, GJ TI HIV TESTING - STATE-OF-THE-ART SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; AIDS-RELATED COMPLEX; AT-RISK INDIVIDUALS; BLOOD-DONORS; WESTERN BLOT; SEXUAL PARTNERS; HOMOSEXUAL MEN; SEROPOSITIVE INDIVIDUALS; SEROLOGICAL MARKERS C1 NIDA,ROCKVILLE,MD. RP SLOAND, EM (reprint author), NHLBI,BLDG 31,ROOM 5A21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 95 TC 55 Z9 55 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 NOV 27 PY 1991 VL 266 IS 20 BP 2861 EP 2866 DI 10.1001/jama.266.20.2861 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GQ722 UT WOS:A1991GQ72200035 PM 1942454 ER PT J AU PAUL, IA DUNCAN, GE MUELLER, RA HONG, JS BREESE, GR AF PAUL, IA DUNCAN, GE MUELLER, RA HONG, JS BREESE, GR TI NEURAL ADAPTATION IN RESPONSE TO CHRONIC IMIPRAMINE AND ELECTROCONVULSIVE SHOCK - EVIDENCE FOR SEPARATE MECHANISMS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ANTIDEPRESSANTS; IMIPRAMINE; ELECTROCONVULSIVE SHOCK; BETA-ADRENOCEPTORS; 5-HT2 RECEPTORS; DYNORPHIN; THYROTROPIN-RELEASING HORMONE (TRH) ID BETA-ADRENERGIC RECEPTORS; THYROTROPIN-RELEASING-HORMONE; ANTI-DEPRESSANT TREATMENT; FORCED SWIM TEST; RAT-BRAIN; BINDING-SITES; SEROTONIN-2 RECEPTORS; H-3 DIHYDROALPRENOLOL; ADRENOCEPTORS; HYPOTHESIS AB The effects of chronic imipramine and electroconvulsive shock alone or combined were assessed on rat brain beta-adrenoceptors and serotonin2 (5-HT2) receptors and on dynorphin and thyrotropin releasing hormone (TRH) levels. These treatments resulted in regionally discrete and treatment-specific patterns of change in beta-adrenoceptor and 5-HT2 receptor density and in TRH and dynorphin levels. Electroconvulsive shock eliminated the serotonergic component of hippocampal DHA binding, suggesting an effect of this treatment on 5-HT1 receptors. The effects of combined electroconvulsive shock and imipramine treatments on cortical 5-HT2 and beta-adrenoceptor density appeared to be the additive sum of the individual treatment effects. No treatment interaction was observed on hippocampal 5-HT2 and beta-adrenoceptors, except after day 2. No treatment interaction on peptide content was observed at any time. These results demonstrate independent anatomical specificity for the effects of electroconvulsive shock and imipramine and provide evidence that the mechanisms responsible for their antidepressant actions differ. C1 UNIV N CAROLINA,SCH MED,BIOL SCI RES CTR 223,CB 7250,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH MED,MENTAL HLTH CLIN RES,CHAPEL HILL,NC 27599. NIEHS,BEHAV & NEURAL TOXICOL LAB,RES TRIANGLE PK,NC 27703. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. RP DUNCAN, GE (reprint author), UNIV N CAROLINA,SCH MED,BIOL SCI RES CTR 223,CB 7250,CHAPEL HILL,NC 27599, USA. FU NICHD NIH HHS [HD-03110]; NIMH NIH HHS [MH-33127, MH-39144] NR 32 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 26 PY 1991 VL 205 IS 2 BP 135 EP 143 DI 10.1016/0014-2999(91)90811-4 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GU490 UT WOS:A1991GU49000003 PM 1687466 ER PT J AU CHAKRABORTI, PK GARABEDIAN, MJ YAMAMOTO, KR SIMONS, SS AF CHAKRABORTI, PK GARABEDIAN, MJ YAMAMOTO, KR SIMONS, SS TI CREATION OF SUPER GLUCOCORTICOID RECEPTORS BY POINT MUTATIONS IN THE STEROID BINDING DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TISSUE-CULTURE CELLS; DEXAMETHASONE 21-MESYLATE; FUNCTIONAL DOMAINS; AMINO-ACID; HORMONE; IDENTIFICATION; EXPRESSION; COVALENT; ARSENITE; FRAGMENT AB Almost all modifications of the steroid binding domain of glucocorticoid receptors are known to cause a reduction or loss of steroid binding activity. Nonetheless, we now report that mutations of cysteine 656 of the rat receptor, which was previously suspected to be a crucial amino acid for the binding process, have produced "super" receptors. These receptors displayed an increased affinity for glucocorticoid steroids and a decreased relative affinity for cross-reacting steroids such as progesterone and aldosterone. The increased in vitro affinity of the super receptors was maintained in a whole cell bioassay. These results indicate that additional modifications of the glucocorticoid receptor, and probably the other steroid receptors, may further increase the binding affinity and/or specificity. C1 NIDDKD,STEROID HORMONES SECT,BLDG 8,RM B2A-07,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM,SAN FRANCISCO,CA 94143. NR 33 TC 86 Z9 88 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22075 EP 22078 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400003 PM 1939229 ER PT J AU STADTMAN, TC DAVIS, JN AF STADTMAN, TC DAVIS, JN TI GLYCINE REDUCTASE PROTEIN-C - PROPERTIES AND CHARACTERIZATION OF ITS ROLE IN THE REDUCTIVE CLEAVAGE OF SE-CARBOXYMETHYL-SELENOPROTEIN-A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACETYL PHOSPHATE; PURIFICATION; SELENOCYSTEINE; COMPLEX; IDENTIFICATION; INTERMEDIATE; COMPONENTS; SYSTEM AB The clostridial glycine reductase complex catalyzes the reductive deamination of glycine in an energy-conserving process that results in the esterification of orthophosphate. The complex consists of three protein components: selenoprotein A; protein B, a carbonyl group protein; and protein C, a sulfhydryl protein. The protein C component also catalyzes the arsenate-dependent decomposition of acetyl phosphate. Reaction of protein C with iodoacetate inhibits its ability to decompose acetyl phosphate, but this inactivation of the enzyme by alkylation is prevented in the presence of the substrate indicating the formation of an unreactive enzyme-bound acetylthiol ester. The Se-carboxymethylselenocysteine residue of the selenoprotein A component of glycine reductase was generated by selective alkylation of the ionized selenol group at pH 6 with [C-14]bromoacetate. Using this pure alkylated selenoprotein A as substrate, it was shown that protein C catalyzes the conversion of the [C-14]carboxymethyl group, in selenoether linkage to protein A, to [C-14] acetate in the presence of arsenate, dithiothreitol, and Mg2+. A procedure using hydrophobic chromatographic matrices was developed for the large scale isolation of protein C, and a number of the properties of the enzyme were determined. C1 NHLBI,BIOCHEM LAB,BLDG 3,ROOM 108,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 28 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22147 EP 22153 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400016 PM 1939235 ER PT J AU GRAHAME, DA AF GRAHAME, DA TI CATALYSIS OF ACETYL-COA CLEAVAGE AND TETRAHYDROSARCINAPTERIN METHYLATION BY A CARBON-MONOXIDE DEHYDROGENASE-CORRINOID ENZYME COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWN METHANOSARCINA-THERMOPHILA; AUTOTROPHIC GROWTH; CELL-EXTRACTS; ACETOGENIC BACTERIA; METHANE FORMATION; COENZYME-A; ACETATE; BARKERI; PURIFICATION; PATHWAY AB An enzyme complex containing carbon monoxide dehydrogenase and a corrinoid protein has been isolated from Methanosarcina barkeri. Sodium dodecyl sulfate-gel electrophoresis revealed five polypeptides of molecular masses-alpha = 19,700, beta = 84,500, gamma = 63,200, delta = 53,000, and epsilon = 51,400 Da in equimolar amounts. One mol of cobamide cofactor was found per minimal alpha-beta-gamma-delta-epsilon unit. The molecular mass of the native complex was 1,600,000 Da by high pressure liquid chromatography (HPLC) gel filtration, which suggested an alpha-6-beta-6-gamma-6-delta-6-epsilon-6 oligomeric structure. Catalysis of a reaction involving cleavage of acetyl-CoA and methylation of tetrahydrosarcinapterin was indicated by spectrophotometric analyses; a time-dependent absorption decrease in the 300-320 nm region was observed in the complete reaction mixture which contained acetyl-CoA, tetrahydrosarcinapterin, and the enzyme complex. In control samples lacking any one of the these components the absorption spectrum remained virtually unaltered. Reversed-phase HPLC analysis confirmed that tetrahydrosarcinapterin was converted to a product that co-eluted with authentic methyltetrahydrosarcinapterin. The product also exhibited the UV-visible absorption spectrum expected for methyltetrahydrosarcinapterin. Free CoA was identified as an additional product of the reaction. The carbonyl group of acetyl-CoA was oxidized to carbon dioxide. Spectral changes indicated concomitant Fe/S center reduction. Production of CoA was essentially stoichiometric with methyltetrahydrosarcinapterin formation and tetrahydrosarcinapterin consumption. Analyses during purification showed that catalytic activity was restricted exclusively to the fractions that contained the carbon monoxide dehydrogenase-corrinoid enzyme complex. RP GRAHAME, DA (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,RM 114,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 79 Z9 83 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22227 EP 22233 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400028 PM 1939246 ER PT J AU BURBELO, PD BRUGGEMAN, LA GABRIEL, GC KLOTMAN, PE YAMADA, Y AF BURBELO, PD BRUGGEMAN, LA GABRIEL, GC KLOTMAN, PE YAMADA, Y TI CHARACTERIZATION OF A CIS-ACTING ELEMENT REQUIRED FOR EFFICIENT TRANSCRIPTIONAL ACTIVATION OF THE COLLAGEN-IV ENHANCER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASEMENT-MEMBRANE COMPONENTS; DNA-BINDING PROTEINS; HEAD-TO-HEAD; PROMOTER REGION; GENE-EXPRESSION; BIDIRECTIONAL PROMOTER; CHAIN; IDENTIFICATION; ALPHA-1(IV); CELLS AB Two regulatory regions in the murine collagen IV enhancer were identified. Transient transfection assays delimited a 210-base pair fragment within the first intron of the alpha-1(IV) collagen gene that had significant transcriptional enhancer activity. DNase I protection and gel mobility shift confirmed that two regions, designated footprints A and B, within this fragment bound nuclear factors. Gel shift studies suggested that the CCTTATCTCTGATGG motif (A-34) in the footprint A region was important for specific nuclear factor binding. Mutations in the A-34 motif abolished factor binding as detected by gel shift and resulted in a significant decrease in enhancer activity in transient transfection assays of F9 teratocarcinoma cells. Two putative transcription factors of M(r) = 37,000 and M(r) = 94,000, which interact with the A-34 motif, were purified from Engelbreth-Holm-Swarm tumor tissue using DEAE-Sephacel, heparin-Sepharose, salmon sperm DNA-Sepharose, and specific A-34 oligonucleotide affinity chromatography. Southwestern analysis revealed that both of these factors were capable of binding the A-34 oligonucleotide directly and did not require additional subunits for binding. These data suggest that positively acting transcription factor(s) interact with the A-34 site in the enhancer and are required for efficient transcription of the alpha-1 and alpha-2(IV) collagen chain genes. RP BURBELO, PD (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Burbelo, Peter/B-1027-2009 NR 29 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22297 EP 22302 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400039 PM 1939251 ER PT J AU BARBOSA, P WISTOW, GJ CIALKOWSKI, M PIATIGORSKY, J OBRIEN, WE AF BARBOSA, P WISTOW, GJ CIALKOWSKI, M PIATIGORSKY, J OBRIEN, WE TI EXPRESSION OF DUCK LENS DELTA-CRYSTALLIN CDNAS IN YEAST AND BACTERIAL HOSTS - DELTA-2-CRYSTALLIN IS AN ACTIVE ARGININOSUCCINATE LYASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHEMICAL PROPERTIES; STRUCTURAL PROTEIN; ENZYME-CRYSTALLINS; GENE; SEQUENCE; LIVER; RECRUITMENT; POLYMERASE; EVOLUTION; CLONING AB The major soluble protein in the lenses of most birds and reptiles is delta-crystallin. In chickens and ducks the delta-crystallin gene has duplicated, and in the duck both genes contribute to the protein in the lens, while in the chicken lens there is a great preponderance of the delta-1 gene product. Purified delta-crystallin has previously been shown to possess the enzymatic activity of argininosuccinate lyase. In order to determine the enzymatic properties of the two duck delta-crystallins their corresponding cDNA molecules were placed in yeast and bacterial expression plasmids. In Saccharomyces cerevisiae, the activity of each crystallin was assessed by transformation of the expression plasmids into a strain deficient for argininosuccinate lyase activity. The ability of the resulting yeast to grow on arginine deficient medium was used as a measure of enzymatic activity. Yeast expressing the duck delta-2-crystallin protein grew rapidly, while those expressing delta-1-crystallin failed to grow. Enzyme activity measurements confirmed the presence of activity in the delta-2-crystallin-expressing yeast, and no detectable activity could be demonstrated in the delta-1-crystallin-expressing yeast. Northern blotting of RNA from the transformed yeast revealed equal levels of mRNA species from the two constructs. For further analysis, the delta-2-crystallin cDNA was placed in the bacterial expression plasmid, pET-3d. The delta-2-crystallin protein produced in Escherichia coli was purified to homogeneity and analyzed to determine the kinetic properties. A K(m) of 0.35 mM was determined for argininosuccinate and a V(m) of 3.5-mu-mol/min/mg was determined. These data demonstrate that, following duplication of the primordial argininosuccinate lyase gene, one of the genes maintained its role as an enzyme (delta-2-crystallin) while also serving as a crystallin and the other has evolved to specialize as a structural protein in the lens (delta-1-crystallin), presumably losing most or all of its catalytic capacity. C1 BAYLOR COLL MED,INST MOLEC GENET,1 BAYLOR PLAZA,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT BIOCHEM,HOUSTON,TX 77030. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY07612] NR 43 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22319 EP 22322 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400043 PM 1718993 ER PT J AU YANG, LJ BAFFY, G RHEE, SG MANNING, D HANSEN, CA WILLIAMSON, JR AF YANG, LJ BAFFY, G RHEE, SG MANNING, D HANSEN, CA WILLIAMSON, JR TI PERTUSSIS TOXIN-SENSITIVE GI PROTEIN INVOLVEMENT IN EPIDERMAL GROWTH FACTOR-INDUCED ACTIVATION OF PHOSPHOLIPASE C-GAMMA IN RAT HEPATOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL 12-MYRISTATE 13-ACETATE; INOSITOL PHOSPHATE GENERATION; TYROSINE PHOSPHORYLATION; FACTOR RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS; KINASE-C; DIFFERENTIAL MECHANISMS; SIGNAL TRANSDUCTION; ANGIOTENSIN-II; CELLS AB Treatment of rat hepatocytes with epidermal growth factor (EGF) produced an enhanced tyrosine phosphorylation of the EGF receptor and phospholipase C-gamma (PLC-gamma) in conjunction with the mobilization of Ca2+. Approximately 30% of the total PLC-gamma was tyrosine-phosphorylated with a maximum being reached after 30 s of incubation with EGF. Pretreatment of the rats with pertussis toxin prior to isolation of the hepatocytes blocked EGF-induced tyrosine phosphorylation of PLC-gamma and Ca2+ mobilization but had no effect on autophosphorylation of the EGF receptor or Ca2+ responses elicited by angiotensin II or phenylephrine. Under these conditions G(i) protein alpha-subunits were fully ADP-ribosylated. A 41-kDa G(i) protein alpha-subunit was found to be present in the anti-PLC-gamma immune complex after EGF stimulation as shown by in vitro ADP-ribosylation using [P-32]NAD+ and activated pertussis toxin. The kinetics of association between PLC-gamma with G(i)alpha protein reached a maximum after 1 min of incubation with EGF. Antibodies specific for the EGF receptor also coimmunoprecipitated a G(i) protein alpha-subunit. Treatment of hepatocytes with EGF caused first an increase and then a decrease in the amount of G(i) protein alpha-subunit associated with the EGF receptor. In contrast, studies with cultured rat liver (WB) cells, a cell line in which EGF stimulation of phosphoinositide hydrolysis is not inhibited by pertussis toxin, showed that a stable complex of G(i)alpha was not formed with either PLC-gamma or EGF receptor immunoprecipitates. These results indicate that a pertussis toxin-sensitive G(i) protein is uniquely involved in the signal transduction pathway mediating EGF-induced activation of PLC-gamma and Ca2+ mobilization in hepatocytes. C1 UNIV PENN,DEPT BIOCHEM & BIOPHYS,601 GODDARD LABS,37TH & HAMILTON WALK,PHILADELPHIA,PA 19104. GEISINGER MED CLIN,DANVILLE,PA 17822. UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-15120] NR 44 TC 119 Z9 119 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22451 EP 22458 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400063 PM 1657996 ER PT J AU ABRAMIC, M LEVINE, AS PROTIC, M AF ABRAMIC, M LEVINE, AS PROTIC, M TI PURIFICATION OF AN ULTRAVIOLET-INDUCIBLE, DAMAGE-SPECIFIC DNA-BINDING PROTEIN FROM PRIMATE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XERODERMA-PIGMENTOSUM-CELLS; ESCHERICHIA-COLI; HUMAN-FIBROBLASTS; NUCLEAR EXTRACTS; APURINIC SITES; HUMAN-PLACENTA; HELA-CELLS; REPAIR; ENDONUCLEASE; EXCINUCLEASE AB A UV-inducible, damage-specific DNA-binding (DDB) protein with high affinity for double-stranded UV-irradiated DNA has been identified recently in monkey kidney (CV-1) cells (Hirschfeld, S., Levine, A. S., Ozato, K., and Protic, M. (1990) Mol. Cell. Biol. 10, 2041-2048). We have now purified the DDB protein from extracts of CV-1 cells using hydroxylapatite, phosphocellulose, Mono S, and DNA-affinity column chromatography. The DDB activity, either from mock-treated or UV-induced cells, is heterodisperse in column chromatography, and separation of three forms of the protein was obtained on a phosphocellulose column. Analysis of purified preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that > 90% of all three forms is a protein of approximately 126 kDa. The size of the native DDB protein was deduced from gel filtration and native polyacrylamide gel electrophoresis to be approximately 210 kDa, which suggests that the native DDB protein in solution is a homodimer. Preparations of partially purified DDB protein from UV-treated cells have enhanced levels of DDB activity and the protein when compared with similar preparations from mock-treated cells. This damage-recognition protein, alone or in conjunction with other subunits, may be of general importance for the initial recognition of DNA damage in mammals. C1 NICHHD, VIRUSES & CELLULAR BIOL SECT, BETHESDA, MD 20892 USA. NR 39 TC 59 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22493 EP 22500 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400069 PM 1657999 ER PT J AU FINBLOOM, DS WAHL, LM WINESTOCK, KD AF FINBLOOM, DS WAHL, LM WINESTOCK, KD TI THE RECEPTOR FOR INTERFERON-GAMMA ON HUMAN PERIPHERAL-BLOOD MONOCYTES CONSISTS OF MULTIPLE DISTINCT SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GEL-ELECTROPHORESIS; LIGAND-BINDING; IFN-GAMMA; EXPRESSION; GLYCOSYLATION; PROTEINS; CHROMOSOME-6; MACROPHAGES; ANTIBODIES; FRACTIONS AB The interaction of interferon-gamma (IFN-gamma) (a product of activated T lymphocytes) and monocytes is essential for immune responsiveness, host defense, and chronic inflammation. In this report we define the IFN-gamma receptor (IFN-gamma-R) on human monocytes as a receptor complex consisting of at least three subunits. Solubilization and immunoprecipitation of [S-35]methionine- and [S-35]cysteine-labeled monocytes were optimized by controlling the detergent concentration during solubilization and washing of the immunoprecipitates. This enabled subunits to be coimmunoprecipitated by several different anti-IFN-gamma-R antibodies raised against the 90-kDa cloned binding protein. Immunoprecipitation under stringent (1% sodium dodecyl sulfate) conditions resulted in the visualization of only the 80-90-kDa binding protein. Under less stringent conditions at least two coimmunoprecipitated subunits (molecular mass of 200 and 38 kDa) were consistently associated with the 80-kDa (90-92 kDa reduced) binding protein. The 38-kDa subunit was shown to be distinct from the 80-kDa subunit by proteolytic fragment analysis. Cross-linking of I-125-rIFN-gamma to monocytes yielded receptor-IFN-gamma complexes consistent with the existence of multiple subunits. C1 NIDR, CELLULAR IMMUNOL LAB, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT CHEM, BETHESDA, MD 20814 USA. RP US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 26 TC 12 Z9 13 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 NOV 25 PY 1991 VL 266 IS 33 BP 22545 EP 22548 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400076 PM 1834673 ER PT J AU ALBER, G MILLER, L JELSEMA, CL VARINBLANK, N METZGER, H AF ALBER, G MILLER, L JELSEMA, CL VARINBLANK, N METZGER, H TI STRUCTURE-FUNCTION-RELATIONSHIPS IN THE MAST-CELL HIGH-AFFINITY RECEPTOR FOR IGE - ROLE OF THE CYTOPLASMIC DOMAINS AND OF THE BETA-SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E; HISTAMINE-RELEASE; TRANSFECTED CELLS; INSULIN-RECEPTORS; BINDING; EXPRESSION; PHOSPHORYLATION; PROTEIN AB To define functionally critical regions of the high affinity receptor for IgE (Fc-epsilon-RI), we stably transfected P815 cells with mutated cDNAs coding for subunits with truncated cytoplasmic domains (CD). In addition, to examine further the role of the beta-subunit, stable transfectants expressing chimeric Fc-epsilon-RI without beta-subunits were generated. Transfectants were tested for receptor-mediated changes in intracellular Ca2+, for stimulated hydrolysis of phosphoinositides, and for protein tyrosine phosphorylation. In all cases these biochemical signals were affected coordinately, suggesting that they are coupled, possibly in a single pathway. Truncation of the alpha-subunit or of the NH2-terminal CD of the beta-subunit had no effect, but Fc-epsilon-RIs with beta-subunits missing the COOH-terminal CD were inactive. Interestingly, receptors in cells transfected only with human Fc-epsilon-RI(alpha) (which utilize the gamma-chains endogenously synthesized by the P815 cells but which contain no beta-subunits) responded normally. Therefore, the beta-subunit influences the functions studied but is not essential. Although structural analysis excluded a straightforward mechanism, truncation of the CD of the gamma-chain led to loss of signaling. C1 NIAMSD,BETHESDA,MD 20892. NR 36 TC 173 Z9 174 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22613 EP 22620 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400085 PM 1658002 ER PT J AU THOMPSON, J SACKETT, DL DONKERSLOOT, JA AF THOMPSON, J SACKETT, DL DONKERSLOOT, JA TI PURIFICATION AND PROPERTIES OF FRUCTOKINASE-I FROM LACTOCOCCUS-LACTIS - LOCALIZATION OF SCRK ON THE SUCROSE-NISIN TRANSPOSON TN5306 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STREPTOCOCCUS-MUTANS; PHOSPHOTRANSFERASE SYSTEM; NUCLEOTIDE-SEQUENCE; KLEBSIELLA-PNEUMONIAE; BACILLUS-SUBTILIS; ZYMOMONAS-MOBILIS; SUCRASE GENE; PHOSPHOENOLPYRUVATE; METABOLISM; ESCHERICHIA-COLI-K12 AB Two electrophoretically distinct proteins with fructokinase (ATP: fructose-6-phosphotransferase) activity were detected in Lactococcus lactis subsp. lactis K1. Whereas fructokinase I was induced specifically by growth of the organism on sucrose, fructokinase II was derepressed during growth on ribose, galactose, maltose, and lactulose. Fructokinase I was purified about 1000-fold to electrophoretic homogeneity (specific activity 112 units/mg). The amino acid composition, N-terminal sequence, nucleoside triphosphate, and metal requirement(s) of the enzyme are reported. Ultracentrifugal analysis showed that the enzyme was primarily dimeric with subunits of 33.5 kDa (+/- 5%). When completely reduced, fructokinase I migrated as a single protein (M(r) = 32,000) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but in the absence of reducing agent two polypeptides (apparent M(r) = 29,000 and 3 1,000) were detected. Isoelectric focusing also revealed two polypeptides (pI 5.6 and 5.8), and both species catalyzed the phosphorylation of fructose and mannose. Hybridization studies showed that: (i) a sucrose-negative mutant lacking the fructokinase I gene (scrK) retained fructokinase II activity and (ii) scrK is closely linked to scrA and scrB which encode Enzyme II(Ser) and sucrose-6-phosphate hydrolase, respectively. In L. lactis K1, these genes and the N5-(1-carboxyethyl)-L-ornithine synthase gene (ceo) are encoded on the sucrose-nisin transposon Tn5306 in the order ceo-scrKAB. C1 NIADDKD,BETHESDA,MD 20892. RP THOMPSON, J (reprint author), NIDR,MICROBIAL ECOL LAB,BLDG 30,RM 528,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 28 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1991 VL 266 IS 33 BP 22626 EP 22633 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR564 UT WOS:A1991GR56400087 PM 1658003 ER PT J AU BERKHOUT, B JEANG, KT AF BERKHOUT, B JEANG, KT TI DETAILED MUTATIONAL ANALYSIS OF TAR RNA - CRITICAL SPACING BETWEEN THE BULGE AND LOOP RECOGNITION DOMAINS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; ACTIVATION-RESPONSIVE REGION; TRANS-ACTIVATION; TRANSCRIPTIONAL ACTIVATION; FUNCTIONAL DOMAINS; BASIC DOMAIN; PROTEIN; HIV-1; TYPE-1 AB Trans-activation of HIV-1 by the Tat protein is mediated through a cis-acting element (TAR) in the viral RNA. In order to obtain further insight into the molecular interactions for trans-activation, a detailed mutational analysis of TAR RNA was carried out. TAR RNA forms a hairpin structure with important sequence elements in the single-stranded bulge- and loop-domains. We found that the sequence of the base-pairs flanking the bulge is critical for Tat-mediated trans-activation. In addition, Tat-response is reduced when the bulge is forced into a base-paired configuration through the introduction of complementary nucleotides on the opposite side of the stem. Thus, the 3-nucleotide bulge and adjacent base-pairs comprise a recognition domain with both sequence- and structure-elements. Accessibility of the loop sequences is also important for Tat function, since base-pairing through the formation of a pseudoknot-like structure does inhibit Tat action. A third critical parameter that influences the magnitude of Tat response is the number of loop nucleotides. Finally, the relative spacing between the loop and the bulge is also important. We introduced additional base-pairs in the stem connecting the two domains. Such mutations progressively decreased the efficiency of Tat induction. Interestingly, activity of the HIV-2 Tat protein did markedly increase on targets with one or two additional basepairs. These results suggest that Tat interacts with a cellular loop-binding protein(s) to increase HIV gene expression. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 51 TC 65 Z9 66 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 NOV 25 PY 1991 VL 19 IS 22 BP 6169 EP 6176 DI 10.1093/nar/19.22.6169 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR785 UT WOS:A1991GR78500014 PM 1956776 ER PT J AU FURTH, PA HENNIGHAUSEN, L BAKER, C BEATTY, B WOYCHICK, R AF FURTH, PA HENNIGHAUSEN, L BAKER, C BEATTY, B WOYCHICK, R TI THE VARIABILITY IN ACTIVITY OF THE UNIVERSALLY EXPRESSED HUMAN CYTOMEGALOVIRUS IMMEDIATE EARLY GENE-1 ENHANCER PROMOTER IN TRANSGENIC MICE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID AMP-RESPONSE ELEMENTS; TRANSCRIPTION FACTORS; REGULATORY REGION; VIRUS ENHANCER; SEQUENCE; CELLS; MUSCLE AB Transcriptional control regions which direct transgene expression to all tissues in transgenic animals can be useful tools for gain-of-function experiments in transgenic animals. A candidate for this purpose is the regulatory region of the human cytomegalovirus immediate early 1 gene (HCMVIE1) which is highly expressed in many lines of tissue culture cells. Here we analyzed the activity of the HCMVIE1 enhancer/promoter using a sensitive reporter gene, the bacterial chloramphenicol acetyltransferase (CAT) gene. Three lines of transgenic mice with an intact transgene were established. All 3 lines expressed the transgene in all 28 tissues analyzed; however, levels of expression between the three lines varied up to 100,000 fold. In addition, expression levels in the high expressing line varied over a 10,000 fold continuum, while expression levels between tissues was almost uniform in the lowest expressing line. The transgene was well expressed in the high expressing line; CAT activity in the highest expressing tissues was equivalent to levels previously reported for tissue specific CAT transgenes active only in a limited number of tissues. These data support the utilization of the HCMVIE1 enhancer/promoter as a means of expressing a transgene in all tissues, but indicate that lines with substantially different overall levels of expression may be generated, and that markedly different levels of tissue specific expression may be found when the overall level of transgene expression is high. C1 NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. RP FURTH, PA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 27 TC 100 Z9 100 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1991 VL 19 IS 22 BP 6205 EP 6208 DI 10.1093/nar/19.22.6205 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR785 UT WOS:A1991GR78500019 PM 1956779 ER PT J AU PHILPOTT, CC ROUAULT, TA KLAUSNER, RD AF PHILPOTT, CC ROUAULT, TA KLAUSNER, RD TI SEQUENCE AND EXPRESSION OF THE MURINE IRON-RESPONSIVE ELEMENT BINDING-PROTEIN SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NICHHD,CELL BIOL & METAB BRANCH,BLDG 18-T,ROOM 101,BETHESDA,MD 20892. NR 7 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1991 VL 19 IS 22 BP 6333 EP 6333 DI 10.1093/nar/19.22.6333 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR785 UT WOS:A1991GR78500044 PM 1956798 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN BETA-1 SUBUNIT OF THE GABA-A RECEPTOR GENE (GABRB1) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 3 TC 6 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 NOV 25 PY 1991 VL 19 IS 22 BP 6345 EP 6345 DI 10.1093/nar/19.22.6345 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR785 UT WOS:A1991GR78500056 PM 1659691 ER PT J AU KEYNES, RD ROJAS, E CENA, V AF KEYNES, RD ROJAS, E CENA, V TI BLOCKING OF THE SODIUM-CHANNEL BY EXTERNAL TRIS IN THE SQUID GIANT-AXON SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article ID CURRENTS AB The macroscopic current carried by Na+ ions was recorded in voltage-clamped squid giant axons that were dialysed with a mixture of CsF and NaF, and bathed in chloride solutions in which the sodium current (I(Na)) was reduced by partly blocking the sodium channels with tetrodotoxin, or by replacing four fifths of the Na+ either with choline or with tris buffer at pH 7.3. The permeability coefficient (P(Na,fast)) for the fast-inactivating current was unchanged on substitution of choline for sodium in the bathing solution, but in the high-Tris bathing solution, P(Na,fast) was reduced in a voltage-dependent manner, so that the permeability relative to normal rose from 0.2 at -40 mV to 0.8 at + 100 mV. The coefficient P(Na,non) for the non-inactivating current behaved in a similar way, except that the permeability ratio fell between test potentials of -40 and +10 mV instead of rising. The blocking effect of Tris was unaffected by temperature, but there was some interaction with that of internal tetramethylammonium ions. C1 STN BIOL ROSCOFF, F-29682 ROSCOFF, FRANCE. NIDDK, BETHESDA, MD 20892 USA. UNIV ALICANTE, DEPT NEUROQUIM, E-03080 ALICANTE, SPAIN. RP KEYNES, RD (reprint author), PHYSIOL LAB, CAMBRIDGE CB2 3EG, ENGLAND. NR 15 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD NOV 22 PY 1991 VL 246 IS 1316 BP 129 EP 133 DI 10.1098/rspb.1991.0134 PG 5 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA GT250 UT WOS:A1991GT25000005 ER PT J AU AARONSON, SA AF AARONSON, SA TI GROWTH-FACTORS AND CANCER SO SCIENCE LA English DT Article ID PROTEIN-TYROSINE KINASE; GTPASE-ACTIVATING PROTEIN; PHOSPHOLIPASE-C-GAMMA; RETINOBLASTOMA SUSCEPTIBILITY GENE; THYROID PAPILLARY CARCINOMAS; PC12 PHEOCHROMOCYTOMA CELLS; FACTOR RECEPTOR GENES; SIMIAN SARCOMA-VIRUS; PDGF BETA-RECEPTOR; FACTOR-I RECEPTOR AB Signaling pathways that mediate the normal functions of growth factors are commonly subverted in cancer. Oncogenes identified by a variety of approaches have been shown to function at critical steps in mitogenic signaling. Progression through the cell cycle requires the coordinated actions of members of two complementary classes of growth factors, and oncogenes appear to replace the actions of one set of these growth factors. Growth factors can also influence normal cell differentiation, and constitutive activation of growth-promoting pathways in cancer cells can modulate the cell phenotype as well. Paracrine actions of growth factors and cytokines may also influence the stepwise series of genetic events that lead to malignancy. New approaches for cancer therapy are being developed that intervene at various steps in growth factor signaling pathways. RP AARONSON, SA (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 254 TC 1167 Z9 1182 U1 3 U2 29 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1991 VL 254 IS 5035 BP 1146 EP 1153 DI 10.1126/science.1659742 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GQ834 UT WOS:A1991GQ83400033 PM 1659742 ER PT J AU PASTAN, I FITZGERALD, D AF PASTAN, I FITZGERALD, D TI RECOMBINANT TOXINS FOR CANCER-TREATMENT SO SCIENCE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; RICIN-A-CHAIN; EXOTOXIN FUSION PROTEIN; HUMAN OVARIAN-CANCER; NUDE-MOUSE MODEL; T-CELL LEUKEMIA; PSEUDOMONAS EXOTOXIN; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES AB Recombinant toxins target cell surface receptors and antigens on tumor cells. They kill by mechanisms different from conventional chemotherapy, so that cross resistance to conventional chemotherapeutic agents should not be a problem. Furthermore, they are not mutagens and should not induce secondary malignancies or accelerate progression of benign malignancies. They can be mass-produced cheaply in bacteria as homogeneous proteins. Either growth factor-toxin fusions or antibody-toxin fusions can be chosen, depending on the cellular target. RP PASTAN, I (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 90 TC 281 Z9 287 U1 0 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1991 VL 254 IS 5035 BP 1173 EP 1177 DI 10.1126/science.1683495 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GQ834 UT WOS:A1991GQ83400037 PM 1683495 ER PT J AU DONALDSON, JG KAHN, RA LIPPINCOTTSCHWARTZ, J KLAUSNER, RD AF DONALDSON, JG KAHN, RA LIPPINCOTTSCHWARTZ, J KLAUSNER, RD TI BINDING OF ARF AND BETA-COP TO GOLGI MEMBRANES - POSSIBLE REGULATION BY A TRIMERIC G-PROTEIN SO SCIENCE LA English DT Article ID ADENYLATE-CYCLASE; ADP-RIBOSYLATION; CHOLERA-TOXIN; BREFELDIN-A; TRANSPORT; SECRETION; COMPONENT; PURIFICATION; APPARATUS; SUGGESTS AB The binding of cytosolic coat proteins to organelles may regulate membrane structure and traffic. Evidence is presented that a small guanosine triphosphate (GTP)-binding protein, the adenosine diphosphate ribosylation factor (ARF), reversibly associates with the Golgi apparatus in an energy, GTP, and fungal metabolite brefeldin A (BFA)-sensitive manner similar to, but distinguishable from, the 110-kilodalton cytosolic coat protein beta-COP. Addition of beta-gamma-subunits of G proteins inhibited the association of both ARF and beta-COP with Golgi membranes that occurred upon incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Thus, heterotrimeric G proteins may function to regulate the assembly of coat proteins onto the Golgi membrane. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP DONALDSON, JG (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 33 TC 321 Z9 323 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1991 VL 254 IS 5035 BP 1197 EP 1199 DI 10.1126/science.1957170 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GQ834 UT WOS:A1991GQ83400045 PM 1957170 ER PT J AU CHENG, SWC LYNCH, EC LEASON, KR COURT, DL SHAPIRO, BA FRIEDMAN, DI AF CHENG, SWC LYNCH, EC LEASON, KR COURT, DL SHAPIRO, BA FRIEDMAN, DI TI FUNCTIONAL IMPORTANCE OF SEQUENCE IN THE STEM-LOOP OF A TRANSCRIPTION TERMINATOR SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; OPERON ATTENUATOR; GENE-EXPRESSION; RNA-POLYMERASE; NINR REGION; EFFICIENCY; PROMOTERS; PROTEIN; SITES AB Intrinsic transcription terminators of prokaryotes are distinguished by a common RNA motif: a stem-loop structure high in guanine and cytosine content, followed by multiple uridine residues. Models explaining intrinsic terminators postulate that the stem-loop sequence is necessary only to form structure. In the tR2 terminator of coliphage lambda, single-nucleotide changes reducing potential RNA stem stability eliminated tR2 activity, and a compensatory change that restored the stem structure restored terminator activity. However, multiple changes in the stem sequence that should have either maintained or increased stability reduced terminator activity. These results suggest that the ability of the stem-loop structure to signal transcription termination depends on sequence specificity and secondary structure. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,IMAGING PROC SECT,FREDERICK,MD 21701. RI Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI1459-10] NR 41 TC 53 Z9 53 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1991 VL 254 IS 5035 BP 1205 EP 1207 DI 10.1126/science.1835546 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GQ834 UT WOS:A1991GQ83400048 PM 1835546 ER PT J AU BIKOFF, EK JAFFE, L RIBAUDO, RK OTTEN, GR GERMAIN, RN ROBERTSON, EJ AF BIKOFF, EK JAFFE, L RIBAUDO, RK OTTEN, GR GERMAIN, RN ROBERTSON, EJ TI MHC CLASS-I SURFACE EXPRESSION IN EMBRYO-DERIVED CELL-LINES INDUCIBLE WITH PEPTIDE OR INTERFERON SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CARCINOMA-CELLS; GENE-EXPRESSION; MOUSE; ANTIGEN; BETA-2-MICROGLOBULIN; TRANSCRIPTS; MOLECULES; PLACENTA; VECTOR AB IT has long been recognized that the absence of expression of products of the major histocompatibility complex (MHC) during early development might allow the fetus to escape recognition by maternal lymphocytes. In addition to the MHC class I heavy chain and beta-2-microglobulin, antigenic peptide is an essential structural component of the class I molecule 1-5. Indeed, there is evidence that MHC-linked genes encoding peptide transporter molecules 6-10 and possibly components of a proteolytic complex 11,12 are necessary for MHC class I assembly and stability at the cell surface. Here we demonstrate that embryonic cells in general show a defect in MHC class I assembly. Surface expression was rescued in the presence of an appropriate antigenic peptide, or by treatment with interferon. Consistent with this, HAM1 (ref. 9) messenger RNA was not constitutively expressed, but was inducible by interferon, and during differentiation in vitro. Thus, tolerance of the fetal allograft may in part be controlled at the level of peptide-dependent MHC class I assembly. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032. RP BIKOFF, EK (reprint author), CUNY MT SINAI SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,NEW YORK,NY 10029, USA. NR 30 TC 57 Z9 57 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 21 PY 1991 VL 354 IS 6350 BP 235 EP 238 DI 10.1038/354235a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GQ948 UT WOS:A1991GQ94800051 PM 1720508 ER PT J AU SHAPIRO, ED BERG, AT AUSTRIAN, R SCHROEDER, D PARCELLS, V MARGOLIS, A ADAIR, RK CLEMENS, JD AF SHAPIRO, ED BERG, AT AUSTRIAN, R SCHROEDER, D PARCELLS, V MARGOLIS, A ADAIR, RK CLEMENS, JD TI THE PROTECTIVE EFFICACY OF POLYVALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HIGH-RISK PATIENTS; INFLUENZAE TYPE-B; COST-EFFECTIVENESS; PNEUMONIA; IMMUNIZATION; INFECTIONS; CHILDREN; DISEASE AB Background. Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccine's protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. Methods. From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's vaccination history. Results. Thirteen percent of the 1054 case patients and 20 percent of the 1054 matched controls had received pneumococcal vaccine (P < 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P < 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P < 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). Conclusions. Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. UNIV PENN,SCH MED,DEPT RES MED,PHILADELPHIA,PA 19104. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. RP SHAPIRO, ED (reprint author), YALE UNIV,SCH MED,DEPT PEDIAT,333 CEDAR ST,NEW HAVEN,CT 06510, USA. FU NIA NIH HHS [AG04884] NR 38 TC 706 Z9 722 U1 3 U2 19 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 21 PY 1991 VL 325 IS 21 BP 1453 EP 1460 DI 10.1056/NEJM199111213252101 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GQ406 UT WOS:A1991GQ40600001 PM 1944423 ER PT J AU LAGAKOS, S FISCHL, MA STEIN, DS LIM, L VOLBERDING, P AF LAGAKOS, S FISCHL, MA STEIN, DS LIM, L VOLBERDING, P TI EFFECTS OF ZIDOVUDINE THERAPY IN MINORITY AND OTHER SUBPOPULATIONS WITH EARLY HIV-INFECTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONTROLLED TRIAL; AIDS; ANTIGENEMIA; ANTIBODIES; COHORT AB Objective. - The purpose of this study was to determine whether the beneficial effects of zidovudine seen overall in two recently completed placebo-controlled clinical trials are also apparent in blacks, Hispanics, women, and intravenous drug users. Design. - Two double-blind placebo-controlled randomized clinical trials, protocols 016 and 019, conducted by the AIDS Clinical Trials Group. Setting. - University-based referral centers. Participants. - Two thousand forty-eight persons with asymptomatic or mildly symptomatic human immunodeficiency virus infection were analyzed. Of these, 155 were black, 190 were Hispanic, 144 were women, and 221 were intravenous drug users. All randomized subjects were included in the analysis. Intervention. - Participants in the AIDS Clinical Trials Group protocol 016 were assigned to receive a placebo or a 1200-mg daily dose of zidovudine. Participants in the AIDS Clinical Trials Group protocol 019 were assigned to receive a placebo, a 500-mg daily dose of zidovudine, or a 1500-mg daily dose of zidovudine. Main Outcome Measure. - Progression to AIDS. Results. - The rates of progression to AIDS in subjects receiving zidovudine were significantly lower than those in subjects receiving a placebo among blacks (P = .03), whites (relative risk [RR] = 2.3, 95% confidence interval [Cl] = 1.5 to 3.6, P < .0001), Hispanics (RR = 4.4, Cl = 1.2 to 16.8, P =.02), non-Hispanics (RR = 2.3, Cl = 1.5 to 3.6, P =.0002), men (RR = 2.5, Cl = 1.6 to 3.8, P < .0001), and non-intravenous drug users (RR = 2.5, Cl = 1.6 to 4.0, P < .0001). The rates of disease progression for subjects receiving zidovudine were not statistically different from those receiving placebo for women (RR = 3.3, Cl = 0.3 to 36.3, P = .31) or for intravenous drug users (RR = 2.0, Cl = 0.7 to 6.2, P =.21); however, in both instances the estimated RRs were similar to those for men and non-intravenous drug users. Conclusions. - Although the two studies used for this analysis were not specifically designed to assess the effects of zidovudine in each separate subpopulation, the data suggest that the beneficial effects of zidovudine reported for the entire study population also apply to the subpopulations of blacks, Hispanics, women, and intravenous drug users. C1 UNIV MIAMI,DEPT MED,MIAMI,FL 33152. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. RP LAGAKOS, S (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 16 TC 48 Z9 48 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 1991 VL 266 IS 19 BP 2709 EP 2712 DI 10.1001/jama.266.19.2709 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GP691 UT WOS:A1991GP69100025 PM 1942422 ER PT J AU MORSE, RH AF MORSE, RH TI TOPOISOMER HETEROGENEITY OF PLASMID CHROMATIN IN LIVING CELLS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE DNA TOPOLOGY; CHROMATIN; NUCLEOSOME STRUCTURE; TRANSCRIPTION; REPLICATION ID CIRCULAR DNA; TRANSCRIPTION; REPLICATION; NUCLEOSOMES; INVIVO; MINICHROMOSOMES; TOPOLOGY; HISTONES; DENSITY RP MORSE, RH (reprint author), NIDDK,CELLULAR & DEV BIOL LAB,BLDG 6,ROOM B1-26,BETHESDA,MD 20892, USA. OI Morse, Randall/0000-0003-0000-8718 NR 26 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 20 PY 1991 VL 222 IS 2 BP 133 EP 137 DI 10.1016/0022-2836(91)90198-F PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT206 UT WOS:A1991GT20600002 PM 1960716 ER PT J AU CHU, KC KRAMER, BS SMART, CR AF CHU, KC KRAMER, BS SMART, CR TI ANALYSIS OF THE ROLE OF CANCER PREVENTION AND CONTROL MEASURES IN REDUCING CANCER MORTALITY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CERVICAL-CANCER; BREAST-CANCER; STATISTICS; SURVIVAL; TRIAL AB One goal of the war against cancer is to create declines in cancer mortality rates. A decrease in these rates can only occur in two ways: 1) a decrease in incidence rates and 2) a real increase in overall survival rates. Reductions in incidence rates can be envisioned to occur through three mechanisms (in order of the time course of cancer): 1) reduction or amelioration of environmental or lifestyle risk factors, 2) use of agents that prevent the occurrence of cancer by blocking the progression to cancer, and 3) early detection at a preneoplastic state combined with treatment that prevents or delays progression to invasive cancer. "True" increases in overall survival can occur by two mechanisms (in order of the time course of cancer): 1) early detection of cancer by screening tests and subsequent effective treatment and 2) advancements in treatment. Unique patterns or "fingerprints" of stage-specific incidence and overall incidence and of survival rates characterize the various cancer prevention and control mechanisms that can decrease mortality rates. The rates are presented for five organ sites that have shown reduced cancer mortality. The patterns of rates for breast cancer for women under the age of 65 years were most consistent with early detection. The testicular cancer fingerprints were most consistent with advances in treatment, whereas cervical cancer rates were most consistent with the detection of preneoplastic lesions. The stomach cancer fingerprints were indicative of reductions in lifestyle or environmental risks, and colorectal cancer rates were indicative of a combination of treatment advances and early detection. These fingerprint patterns can be extended to other situations in which mortality trends are changing in order to suggest possible causes of observed changes. Limitations of this model are also discussed. RP CHU, KC (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892, USA. NR 21 TC 16 Z9 18 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1991 VL 83 IS 22 BP 1636 EP 1643 DI 10.1093/jnci/83.22.1636 PG 8 WC Oncology SC Oncology GA GQ242 UT WOS:A1991GQ24200013 PM 1749016 ER PT J AU JACOBSEN, SEW RUSCETTI, FW LONGO, DL KELLER, JR AF JACOBSEN, SEW RUSCETTI, FW LONGO, DL KELLER, JR TI ANTINEOPLASTIC DOLASTATINS - POTENT INHIBITORS OF HEMATOPOIETIC PROGENITOR CELLS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID TRANSFORMING GROWTH FACTOR-BETA-1; ANTI-NEOPLASTIC AGENTS; BRYOSTATIN-1; INTERLEUKIN-3; INVITRO; LINES AB Dolastatins 10 and 15, isolated from the shell-less marine mollusk Dolabella auricularia, are potent antineoplastic agents with unknown myelotoxic effects in vivo. The goal of this study was to determine whether the dolastatins inhibit the proliferation of normal hematopoietic progenitor cells. Assays to test inhibition of colony formation and of cell proliferation were performed in vitro with bone marrow cell preparations enriched for progenitor cells and with progenitor cell lines, respectively, using varying drug concentrations and exposure times. Dolastatins 10 and 15 both inhibited human and murine bone marrow cell colony formation in a concentration-dependent manner, with the concentration required for half maximal inhibition ranging from 0.1 to 1 pg/mL for dolastatin 10 and from 10 to 100 pg/mL, for dolastatin 15. These concentrations are 25-fold to 100-fold lower than the concentration required for antineoplastic activity. Complete inhibition of human bone marrow cell colony formation was observed at concentrations of 10-100 pg/mL for dolastatin 10 and 1000-10 000 pg/mL for dolastatin 15. Committed progenitor cells and multipotential progenitor cells were similarly inhibited. The magnitude of inhibition of human hematopoietic cell colony formation was dependent on pre-exposure time to dolastatins 10 and 15, with a reversible effect up to 8 hours and with a 24-hour preincubation resulting in maximal (100%) and irreversible inhibition. Dolastatin 10 at a concentration of 10-100 pg/mL limited the proliferation of six human and four murine hematopoietic progenitor cell lines, as measured by tritiated thymidine incorporation, to between 34% and 83% of that occurring in the absence of the drug. These results indicate that the dolastatins are potent inhibitors of normal hematopoietic progenitor cell proliferation. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21701. RP JACOBSEN, SEW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01CO-74102] NR 21 TC 22 Z9 22 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1991 VL 83 IS 22 BP 1672 EP 1677 DI 10.1093/jnci/83.22.1672 PG 6 WC Oncology SC Oncology GA GQ242 UT WOS:A1991GQ24200018 PM 1749020 ER PT J AU STEIS, RG URBA, WJ KOPP, WC ALVORD, WG SMITH, JW LONGO, DL AF STEIS, RG URBA, WJ KOPP, WC ALVORD, WG SMITH, JW LONGO, DL TI KINETICS OF RECOVERY OF CD4+ T-CELLS IN PERIPHERAL-BLOOD OF DEOXYCOFORMYCIN-TREATED PATIENTS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21701. FU NCI NIH HHS [N01CO-23913, N01CO-74102] NR 6 TC 35 Z9 36 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1991 VL 83 IS 22 BP 1678 EP 1679 DI 10.1093/jnci/83.22.1678 PG 2 WC Oncology SC Oncology GA GQ242 UT WOS:A1991GQ24200019 PM 1684207 ER PT J AU HAN, H RIFKIND, JM MILDVAN, AS AF HAN, H RIFKIND, JM MILDVAN, AS TI ROLE OF DIVALENT-CATIONS IN THE 3',5'-EXONUCLEASE REACTION OF DNA-POLYMERASE-I SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; DEOXYRIBONUCLEIC ACID; COBALT(II) COMPLEXES; CARBONIC-ANHYDRASE; KINETIC MECHANISM; KLENOW FRAGMENT; ACTIVE-SITE; EXONUCLEASE; METALLOENZYMES; INHIBITOR AB X-ray studies of the proofreading 3',5'-exonuclease site of the large (Klenow) fragment of DNA polymerase I have detected a binuclear metal complex consisting of a pentacoordinate metal (site A) which shares a ligand, Asp-355, with an octahedral metal (site B) [Freemont, P. S., Friedman, J. M., Beese, L. S., Sanderson, M. R., & Steitz, T. A. (I 988) Proc. Natl. Acad. Sci. U.S.A. 85, 8924-8928; Beese, L. S., & Steitz, T. A. (1991) EMBO J. 10, 25-33]. Kinetic studies of the activation of the 3',5'-exonuclease reaction by Co2+, Mn2+, or Mg2+, at low concentrations of DNA, reveal sigmoidal activation curves for the three metal ions with Hill coefficients of 2.3-2.4 and K0.5 values of 16.6-mu-M, 4.2-mu-M, and 343-mu-M, respectively. The binding of Co2+ to the enzyme results in the appearance of an intense visible absorption spectrum of the metal ion with maxima at 633, 570, and 524 nm and extinction coefficients of 190, 194, and 150 M-1 cm-1, respectively, suggesting the formation of a pentacoordinate Co2+ complex. Optical titration with Co2+ yields a sigmoidal titration curve which is best fit by assuming the cooperative binding of three Co2+ ions with a K0.5 of 39.9-mu-M, comparable to the value of 16.6-mu-M obtained kinetically. Displacement of Co2+ by 1 equiv of Zn2+, which binds tightly to the A site of the 3',5'-exonuclease, shifts the optical spectrum to 524 nm and lowers the extinction coefficient to 30 M-1 cm-1, indicative of octahedral coordination. EPR spectra of the enzyme-bound Co2+, both in the absence or in the presence of Zn2+ to occlude site A, argue against tetrahedral Co2+ coordination and are consistent with pentacoordinate and octahedral complexation of the metal, as detected optically and by X-ray crystallography. It is suggested that three metal ions bind cooperatively to activate the exonuclease, one of which is pentacoordinate (site A) while the other two are octahedral. The binding of TMP reduces the ligand symmetry at the pentacoordinate site. One of the two octahedrally bound metal ions is probably at site B of the binuclear complex while the other binds nearby and, either directly or indirectly, facilitates the formation of the binuclear complex. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,725 N WOLFE ST,BALTIMORE,MD 21205. NIH,GERONTOL RES CTR,BETHESDA,MD 20892. NR 28 TC 39 Z9 39 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 19 PY 1991 VL 30 IS 46 BP 11104 EP 11108 DI 10.1021/bi00110a012 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GQ586 UT WOS:A1991GQ58600012 PM 1657160 ER PT J AU VISWANADHAN, VN DENCKLA, B WEINSTEIN, JN AF VISWANADHAN, VN DENCKLA, B WEINSTEIN, JN TI NEW JOINT PREDICTION ALGORITHM (Q7-JASEP) IMPROVES THE PREDICTION OF PROTEIN SECONDARY STRUCTURE SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; REFINED CRYSTAL-STRUCTURE; GLOBULAR-PROTEINS; ESCHERICHIA-COLI; BINDING-PROTEIN; RESOLUTION STRUCTURE; TRYPSIN-INHIBITOR; 2.4-A RESOLUTION; LOGICAL ANALYSIS; NEURAL NETWORK AB The classical problem of secondary structure prediction is approached by a new joint algorithm (Q7-JASEP) that combines the best aspects of six different methods. The algorithm includes the statistical methods of Chou-Fasman, Nagano, and Burgess-Ponnuswamy-Scheraga, the homology method of Nishikawa, the information theory method of Garnier-Osgurthope-Robson, and the artificial neural network approach of Qian-Sejnowski. Steps in the algorithm are (i) optimizing each individual method with respect to its correlation coefficient (Q7) for assigning a structural type from the predictive score of the method, (ii) weighting each method, (iii) combining the scores from different methods, and (iv) comparing the scores for alpha-helix, beta-strand, and coil conformational states to assign the secondary structure at each residue position. The present application to 45 globular proteins demonstrates good predictive power in cross-validation testing (with average correlation coefficients per test protein of Q7,alpha = 0.41, Q7,beta = 0.47, Q7,beta = 0.41 for alpha-helix, beta-strand, and coil conformations). By the criterion of correlation coefficient (Q7) for each type of secondary structure, Q7-JASEP performs better than any of the component methods. When all protein classes are included for training and testing (by cross-validation), the results here equal the best in the literature, by the Q7 criterion. More generally, the basic algorithm can be applied to any protein class and to any type of structure/sequence or function/sequence correlation for which multiple predictive methods exist. RP VISWANADHAN, VN (reprint author), NCI,MATH BIOL LAB,BLDG 10,ROOM 4B-56,BETHESDA,MD 20892, USA. NR 96 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 19 PY 1991 VL 30 IS 46 BP 11164 EP 11172 DI 10.1021/bi00110a021 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GQ586 UT WOS:A1991GQ58600021 PM 1932036 ER PT J AU POLLI, JW BILLINGSLEY, ML KINCAID, RL AF POLLI, JW BILLINGSLEY, ML KINCAID, RL TI EXPRESSION OF THE CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE, CALCINEURIN, IN RAT-BRAIN - DEVELOPMENTAL PATTERNS AND THE ROLE OF NIGROSTRIATAL INNERVATION SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE CALCINEURIN; DEVELOPMENT; GAP-43; NEUROMODULIN; DARPP-32; CALMODULIN; PHOSPHATASE ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; BINDING-PROTEIN; KINASE-II; MESSENGER-RNA; GROWTH CONES; IMMUNOCYTOCHEMICAL LOCALIZATION; STIMULATED PHOSPHATASE; CATALYTIC SUBUNIT; DOPAMINE ISLANDS; MOUSE-BRAIN AB The distribution of neurons expressing the calmodulin-dependent protein phosphatase, calcineurin (CN) was characterized in developing and adult rat brain using a combination of immunocytochemical, immunoblot and in situ hybridization approaches. Immunoblot analysis revealed a strong increase postnatally in CN protein expression. Four differently-charged isoforms of CN were observed in adult brain with apparent regional differences in isoform expression. Immunocytochemistry showed highest levels of CN in hippocampus, striatum, substantia nigra, amygdala and septal nuclei with immunoreactivity first appearing in striatum and septal nuclei, followed by hippocampus, neocortex and limbic structures. In situ hybridization demonstrated that mRNA for the catalytic subunit of CN was seen as early as postnatal day (PND) 1 in striatum, cortex and hippocampus. Since immunoreactivity was not detectable until day 4, this suggests that mRNA expression may precede that of protein by several days in these regions. Lesioning of developing and adult nigrostriatal dopamine neurons either with 6-hydroxydopamine or by surgical hemitransection had little effect on expression of CN, suggesting that CN expression is not influenced transsynaptically by dopamine. Collectively, these findings demonstrate that CN protein and mRNA expression are subject to regional and temporal control during brain development suggesting that specific synaptic connections may influence CN gene expression. However, in striatum, dopaminergic innervation does not appear to affect CN levels. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,POB 850,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,CTR CELL & MOLEC BIOL,HERSHEY,PA 17033. NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,IMMUNOL SECT,ROCKVILLE,MD 20852. NR 61 TC 66 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD NOV 19 PY 1991 VL 63 IS 1-2 BP 105 EP 119 DI 10.1016/0165-3806(91)90071-P PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA GT783 UT WOS:A1991GT78300011 ER PT J AU EWAYS, EA ROBERTS, WC AF EWAYS, EA ROBERTS, WC TI CLINICAL AND ANATOMIC OBSERVATIONS IN PATIENTS HAVING MITRAL-VALVE REPLACEMENT FOR MITRAL-STENOSIS AND SIMULTANEOUS TRICUSPID-VALVE REPLACEMENT SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SURGICAL PATHOLOGY AB Certain clinical and morphologic findings are described in 67 patients (aged 23 to 76 years [mean 52]; 55 women [82%]) who had mitral valve replacement for mitral stenosis (with or without associated regurgitation), and simultaneous tricuspid valve replacement for pure tricuspid regurgitation (58 patients) or tricuspid stenosis (all with associated regurgitation; 9 patients). Of the 58 patients with pure tricuspid regurgitation, 21 had anatomically normal and 37 had anatomically abnormal (diffusely fibrotic leaflets) tricuspid valves. Among these 58 patients, no clinical or hemodynamic variable was useful before surgery in distinguishing the group without from that with anatomically abnormal tricuspid valves. All 9 patients with stenotic tricuspid valves had anatomically abnormal tricuspid valves. The latter group had a lower average right ventricular systolic pressure (tricuspid valve closing pressure) than those with pure tricuspid regurgitation, and none had severe pulmonary arterial hypertension (present in 20 [30%] of the 58 patients with pure tricuspid regurgitation). C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 4 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1991 VL 68 IS 13 BP 1367 EP 1371 DI 10.1016/0002-9149(91)90247-I PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GP873 UT WOS:A1991GP87300019 PM 1951127 ER PT J AU STEWART, WF LINET, MS CELENTANO, DD VANNATTA, M ZIEGLER, D AF STEWART, WF LINET, MS CELENTANO, DD VANNATTA, M ZIEGLER, D TI AGE-SPECIFIC AND SEX-SPECIFIC INCIDENCE RATES OF MIGRAINE WITH AND WITHOUT VISUAL AURA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE INCIDENCE; MIGRAINE; POPULATION ID CEREBRAL BLOOD-FLOW; DIFFERENT ENTITIES; HEADACHE; ATTACKS; MEMORY AB Age- and sex-specific incidence rates for the onset of migraine headache with and without preceding visual aura were estimated from a population-based telephone interview survey conducted between March 1986 and June 1987 of 10,169 randomly selected residents of Washington County, Maryland, between the ages of 12 and 29 years. A total of 392 males and 1,018 females were identified as having a history of migraine. Of these, 27% of male cases and 28% of female cases were defined as having migraine with visual aura. Among both males and females, the incidence rate for migraine with visual aura appears to have peaked as much as 3-5 years earlier than the age peak for migraine without aura. For males, the age-specific incidence for migraine with visual aura appears to have peaked on or before 5 years of age at 6.6/1,000 person-years, or possibly higher. In contrast, the highest incidence for migraine without aura occurred between 10 and 11 years of age at 10.1/1,000 person-years. New cases of migraine were uncommon among males in their late 20s. The initial onset of migraine headache begins at a later age among females than among males. For females, the highest incidence of migraine with aura occurred between 12 and 13 years of age at 14.1/1,000 person-years; the highest incidence for migraine without aura occurred between 14 and 17 years of age at 18.9/1,000 person-years. In contrast to males, new onset of migraine was relatively common among females in their late 20s. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,DIV BEHAV SCI & HLTH EDUC,BALTIMORE,MD 21205. UNIV KANSAS,MED CTR,COLL HLTH SCI & HOSP,DEPT NEUROL,KANSAS CITY,KS 66103. RP STEWART, WF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU PHS HHS [N519381] NR 30 TC 222 Z9 224 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1991 VL 134 IS 10 BP 1111 EP 1120 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GV798 UT WOS:A1991GV79800016 PM 1746521 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M PLATO, CC WIGLEY, FM TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M PLATO, CC WIGLEY, FM TOBIN, JD TI FACTORS ASSOCIATED WITH OSTEOARTHRITIS OF THE HAND IN MALES - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE OBESITY; OSTEOARTHRITIS; OSTEOPOROSIS; RISK FACTORS ID OSTEO-ARTHRITIS; JOINT DISEASES; 2ND METACARPAL; GRIP STRENGTH; HAVEN SURVEY; PREVALENCE; DENSITY AB The association of metabolic and physiologic factors with hand osteoarthritis was studied in 888 Caucasian male subjects aged 17-102 years in the Baltimore Longitudinal Study of Aging. Left-hand radiographs taken between 1958 and 1975 were read by one investigator for grade of osteoarthritis using Kellgren-Lawrence scales. Possible risk factors, assessed at the same visit as the last radiograph during this interval, included age and measures of bone mass, body composition, muscle mass, and muscle strength. Results of bivariate analyses of these cross-sectional data showed that increasing grade of hand osteoarthritis was associated with increasing age; greater mean levels of waist/hip ratio and percentage of body fat; and lower mean levels of percentage of cortical area, grip strength, and forearm circumference. After adjustment for age using residuals from best-fit quadratic regression models, none of these independent variables remained significantly associated with grade of hand osteoarthritis. These data fail to support hypotheses that metabolic and physiologic factors are associated with hand osteoarthritis independent of their known age-related changes. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INTERNAL MED,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INTERNAL MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,FRANCIS SCOTT KEY MED CTR,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,BALTIMORE,MD 21205. NR 27 TC 64 Z9 68 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1991 VL 134 IS 10 BP 1121 EP 1127 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GV798 UT WOS:A1991GV79800017 PM 1746522 ER PT J AU HOOVER, DR MUNOZ, A CAREY, V CHMIEL, JS TAYLOR, JMG MARGOLICK, JB KINGSLEY, L VERMUND, SH AF HOOVER, DR MUNOZ, A CAREY, V CHMIEL, JS TAYLOR, JMG MARGOLICK, JB KINGSLEY, L VERMUND, SH TI ESTIMATING THE 1978-1990 AND FUTURE SPREAD OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN SUBGROUPS OF HOMOSEXUAL MEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; MULTICENTER AIDS COHORT; SAN-FRANCISCO; BISEXUAL MEN; KAPLAN-MEIER; HIV SEROCONVERSION; RISK-FACTORS; GAY MEN; INFECTION; PREDICTORS AB The authors studied the historical spread of human immunodeficiency virus type 1 (HIV-1) infection in homosexual/bisexual men and projected its future spread in these men using data from an AIDS-free cohort recruited during late 1984 in Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Dates of preentry seroconversion in HIV-1 seroprevalent men were estimated using study entry values of hematologic variables influenced by HIV-1 infection. The authors used survival methods incorporating truncation to determine numbers/dates of seroconversion for men with a pre-1984 AIDS diagnosis who were selectively excluded by design from the 1984 AIDS-free cohort. Overall, the annual seroconversion hazard rose progressively from 0.4% in 1978 to 13.8% in 1983, dropped to 4.6% in 1985, and remained relatively stable at 1.1-2.2% from 1986 to 1990. By January 1990, almost 46% of men who were seronegative in 1978 had seroconverted. The authors estimated historical rates of spread by city, age, education, and ethnicity to examine the effects of these factors in the early and continuing stages of the HIV-1 epidemic. There were striking differences among cities with respect to pre-1985 seroconversion rates but not with respect to post-1985 seroconversion rates. Age, education, and ethnicity were all associated with 1978-1990 seroconversion rates. Future seroconversion among homosexual men was predicted assuming that the "stabilized" 1986-1990 hazards (stratified by age) observed here will be representative of future rates. Truncated Kaplan-Meier methods gave the probability of a seronegative 20-year-old man's remaining seronegative in subsequent years. Such a man has a 20.2% chance of seroconverting before reaching the age of 25 years (a 4.4% yearly hazard). The annual hazard drops to 2.5% between 25 and 30 years, to about 1.5% between 30 and 45 years, and to 1.0% between 45 and 55 years. The overall probability of seroconversion prior to age 55 years is about 50%, with seroconversion still continuing at and after age 55. Given that this cohort consists of volunteers receiving extensive anti-HIV-1 transmission education, the future seroconversion rates of the general homosexual population may be even higher than those observed here. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21218. NORTHWESTERN UNIV,SCH MED,CANC CTR BIOMETRY SECT,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15260. NIAID,DIV AIDS,EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP HOOVER, DR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,624 N BROADWAY,BALTIMORE,MD 21205, USA. OI Vermund, Sten/0000-0001-7289-8698 NR 36 TC 37 Z9 37 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1991 VL 134 IS 10 BP 1190 EP 1205 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GV798 UT WOS:A1991GV79800024 PM 1746529 ER PT J AU JAIN, VK MAGRATH, IT AF JAIN, VK MAGRATH, IT TI A CHEMILUMINESCENT ASSAY FOR QUANTITATION OF BETA-GALACTOSIDASE IN THE FEMTOGRAM RANGE - APPLICATION TO QUANTITATION OF BETA-GALACTOSIDASE IN IACZ-TRANSFECTED CELLS SO ANALYTICAL BIOCHEMISTRY LA English DT Article RP JAIN, VK (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 4 TC 207 Z9 207 U1 2 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 1991 VL 199 IS 1 BP 119 EP 124 DI 10.1016/0003-2697(91)90278-2 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GQ785 UT WOS:A1991GQ78500019 PM 1807155 ER PT J AU KEDZIE, KM PHILPOT, RM HALPERT, JR AF KEDZIE, KM PHILPOT, RM HALPERT, JR TI FUNCTIONAL EXPRESSION OF MAMMALIAN CYTOCHROMES-P450IIB IN THE YEAST SACCHAROMYCES-CEREVISIAE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; RABBIT LIVER; SELECTIVE INACTIVATION; INDUCIBLE EXPRESSION; CDNA; CELLS; FORMS; CHLORAMPHENICOL; METABOLISM; GENE C1 NIEHS,PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP KEDZIE, KM (reprint author), UNIV ARIZONA,COLL PHARM,DEPT PHARMACOL & TOXICOL,TUCSON,AZ 85721, USA. FU NIEHS NIH HHS [F32 ES05502, ES00151, R01 ES04995] NR 53 TC 37 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1991 VL 291 IS 1 BP 176 EP 186 DI 10.1016/0003-9861(91)90121-X PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM200 UT WOS:A1991GM20000025 PM 1929429 ER PT J AU KLEIN, E ZOHAR, J GERACI, MF MURPHY, DL UHDE, TW AF KLEIN, E ZOHAR, J GERACI, MF MURPHY, DL UHDE, TW TI ANXIOGENIC EFFECTS OF META-CPP IN PATIENTS WITH PANIC DISORDER - COMPARISON TO CAFFEINES ANXIOGENIC EFFECTS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN RECEPTOR HYPERSENSITIVITY; LACTATE PROVOCATION; ANXIETY DISORDERS; SQUIRREL-MONKEYS; HEALTHY-SUBJECTS; NEURO-ENDOCRINE; AGONIST; ATTACKS; BRAIN AB The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind conditions. Both m-CPP and caffeine had significantly greater anxiogenic and panic-inducing effects than placebo, although caffeine produced nonsignificantly greater increases on all anxiety rating scales than m-CPP. Both m-CPP and caffeine produced significant equivalent increases in plasma cortisol concentrations, but only m-CPP produced plasma prolactin increases. These findings provide further evidence implicating both the serotonergic and adenosinergic receptor systems in the neurobiology of panic disorder. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,ROOM 3S239,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 52 TC 78 Z9 81 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1991 VL 30 IS 10 BP 973 EP 984 DI 10.1016/0006-3223(91)90119-7 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GQ048 UT WOS:A1991GQ04800003 PM 1756202 ER PT J AU RAPAPORT, MH DORAN, AR NELSON, DL MCALLISTER, C MAGLIOZZI, JR PAUL, SM AF RAPAPORT, MH DORAN, AR NELSON, DL MCALLISTER, C MAGLIOZZI, JR PAUL, SM TI HALOPERIDOL AND SOLUBLE INTERLEUKIN-2 RECEPTORS SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID ELEVATED LEVELS C1 NCI,METAB BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. NIMH,DIV INTRAMURAL RES,BETHESDA,MD 20892. RP RAPAPORT, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT,LA JOLLA,CA 92093, USA. NR 6 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1991 VL 30 IS 10 BP 1063 EP 1064 DI 10.1016/0006-3223(91)90127-8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GQ048 UT WOS:A1991GQ04800011 PM 1756199 ER PT J AU NOGUCHI, CT BAE, KS CHIN, K WADA, Y SCHECHTER, AN HANKINS, WD AF NOGUCHI, CT BAE, KS CHIN, K WADA, Y SCHECHTER, AN HANKINS, WD TI CLONING OF THE HUMAN ERYTHROPOIETIN RECEPTOR GENE SO BLOOD LA English DT Article ID ERYTHROLEUKEMIC CELL-LINE; COLONY-STIMULATING FACTOR; EXPRESSION CLONING; ERYTHROID-CELLS; BETA-CHAIN; BINDING; TRANSCRIPTION; ACTIVATION; PROTEIN; FAMILY C1 GEORGE MASON UNIV,DEPT BIOL,FAIRFAX,VA 22030. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP NOGUCHI, CT (reprint author), NIDDK,CHEM BIOL LAB,BLDG 10,RM 9N307,BETHESDA,MD 20892, USA. OI Schechter, Alan N/0000-0002-5235-9408 FU NHLBI NIH HHS [2 R44 HL4074402] NR 42 TC 82 Z9 85 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1991 VL 78 IS 10 BP 2548 EP 2556 PG 9 WC Hematology SC Hematology GA GP887 UT WOS:A1991GP88700010 PM 1668606 ER PT J AU HENSON, DE RIES, L FREEDMAN, LS CARRIAGA, M AF HENSON, DE RIES, L FREEDMAN, LS CARRIAGA, M TI RELATIONSHIP AMONG OUTCOME, STAGE OF DISEASE, AND HISTOLOGIC GRADE FOR 22,616 CASES OF BREAST-CANCER - THE BASIS FOR A PROGNOSTIC INDEX SO CANCER LA English DT Article ID SURGICAL ADJUVANT BREAST; INTEROBSERVER REPRODUCIBILITY; HISTOPATHOLOGICAL FEATURES; TUMOR GRADE; SURVIVAL; CARCINOMA; DIFFERENTIATION; INDICATORS; ESTROGEN; RECEPTOR AB Survival rates for 22,616 cases of breast cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were stratified on outcome according to the histologic grade and stage of disease. Two different staging systems, "local, regional, and distant" and a modified American Joint Committee on Cancer (AJCC) system adopted for SEER were used. Relative survival rates were calculated at 5 and 10 years. Patients who were assigned Stage II, Grade 1 had the same survival as those assigned Stage I, Grade 3. Their survival was better than patients assigned Stage I, Grade 4. The 5-year relative survival rate for patients listed as Stage I, Grade 1 was 99% and for patients listed as Stage I, Grade 2, it was 98%. At 10 years, the survival rate of patients assigned Stage I, Grade 1 was 95%. Patients with histologic Grade 1 tumors less than 2 cm in size and with positive axillary lymph nodes had a 5-year survival rate of 99%. As breast tumors increased in size, the histologic grade also increased. The results suggest that in linking histologic grade with stage of disease, the staging system should also be considered. Histologic grade when used in conjunction with stage of disease can improve the prediction of outcome. Our results also indicate that a prognostic index can be created for breast cancer using a combination of stage of disease and histologic grade. The data suggest that only three grades are needed for breast cancer. C1 GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN,ROOM 305,BETHESDA,MD 20892, USA. NR 38 TC 161 Z9 164 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1991 VL 68 IS 10 BP 2142 EP 2149 DI 10.1002/1097-0142(19911115)68:10<2142::AID-CNCR2820681010>3.0.CO;2-D PG 8 WC Oncology SC Oncology GA GL938 UT WOS:A1991GL93800009 PM 1913453 ER PT J AU FUJITA, S PURI, RK YU, ZX TRAVIS, WD FERRANS, VJ AF FUJITA, S PURI, RK YU, ZX TRAVIS, WD FERRANS, VJ TI AN ULTRASTRUCTURAL-STUDY OF INVIVO INTERACTIONS BETWEEN LYMPHOCYTES AND ENDOTHELIAL-CELLS IN THE PATHOGENESIS OF THE VASCULAR LEAK SYNDROME INDUCED BY INTERLEUKIN-2 SO CANCER LA English DT Article ID ACTIVATED KILLER CELLS; HUMAN RECOMBINANT INTERLEUKIN-2; HIGH-DOSE INTERLEUKIN-2; ANTI-TUMOR EFFICACY; TOXICITY; MICE; PROLIFERATION; CANCER; METASTASES; INFUSION AB Lymphokine-activated killer (LAK) cells play a major role in the induction of the vascular leak syndrome (VLS). To understand the mechanism of this syndrome, the authors examined light and electron microscopic alterations in the lung, liver, spleen, kidney, and heart of mice in which VLS was produced by the administration of interleukin-2 (IL-2) (seven injections of 600,000 IU each for a period of 4 days). The results of these studies disclosed that considerable damage had been done to the endothelial cells that consisted of cytoplasmic edema, vacuoles, and myelin figures; in addition, there were frequent sites of transendothelial passage of lymphoid cells, probably IL-2-activated cells, that penetrated through their cytoplasm by means of "temporary migration pores" and accumulated in the perivascular spaces. The results of this study indicate that a direct in vivo interaction between IL-2-activated cells (probably LAK cells) and endothelium results in cytotoxicity to endothelial cells. C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 7N236,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 25 TC 49 Z9 51 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 NOV 15 PY 1991 VL 68 IS 10 BP 2169 EP 2174 DI 10.1002/1097-0142(19911115)68:10<2169::AID-CNCR2820681014>3.0.CO;2-F PG 6 WC Oncology SC Oncology GA GL938 UT WOS:A1991GL93800013 PM 1913455 ER PT J AU ADAMSON, PC BALIS, FM ARNDT, CA HOLCENBERG, JS NARANG, PK MURPHY, RF GILLESPIE, AJ POPLACK, DG AF ADAMSON, PC BALIS, FM ARNDT, CA HOLCENBERG, JS NARANG, PK MURPHY, RF GILLESPIE, AJ POPLACK, DG TI INTRATHECAL 6-MERCAPTOPURINE - PRECLINICAL PHARMACOLOGY, PHASE-I/II TRIAL, AND PHARMACOKINETIC STUDY SO CANCER RESEARCH LA English DT Article ID CEREBROSPINAL-FLUID; RHESUS-MONKEY; MERCAPTOPURINE; LEUKEMIA; METHOTREXATE; INFUSION AB For over 30 years, oral 6-mercaptopurine (6-MP) has been a mainstay of systemic maintenance therapy for acute lymphoblastic leukemia. Despite its efficacy as an antileukemic agent, 6-MP has not been previously administered by the intrathecal (IT) route. In anticipation of a clinical trial of IT 6-MP, preclinical cytotoxicity and pharmacology studies were performed to define a safe, effective dose. The optimal concentration (> 1-mu-M) and duration of exposure (> 12 h) to 6-MP required for cytotoxicity were determined in vitro using human leukemia cell lines. The dose required to achieve the desired cerebrospinal fluid concentrations in humans was derived from pharmacokinetic parameters determined in rhesus monkeys. A phase I/II study was then performed in pediatric patients with refractory meningeal leukemia. Nine patients (aged 3.5 to 16 years) with chronic meningeal leukemia (2 to 6 central nervous system relapses) were entered onto the study. All had previously failed, at a minimum, IT methotrexate, IT cytarabine, and cranial (+/- spinal) radiation. A 10-mg IT dose of 6-MP (calculated to produce cytotoxic cerebrospinal fluid levels for 12 h) was administered twice weekly for 4 weeks. There were four complete responses and three partial responses. The duration of complete responses ranged from 7 to 22 weeks. Observed toxicities were not dose limiting and included mild headache (three patients) and minimal nausea (two patients). Pharmacokinetic studies performed in patients confirmed that cerebrospinal fluid concentrations of 6-MP were > 1-mu-m for 12 h. These results indicate that the IT administration of 6-MP is feasible, is not associated with significant toxicity, and has definite activity in patients with refractory meningeal leukemia. C1 NIH,DEPT PHARM,BETHESDA,MD 20892. CHILDRENS HOSP,LOS ANGELES,CA 90054. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1991 VL 51 IS 22 BP 6079 EP 6083 PG 5 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100010 PM 1933871 ER PT J AU GARBER, JE GOLDSTEIN, AM KANTOR, AF DREYFUS, MG FRAUMENI, JF LI, FP AF GARBER, JE GOLDSTEIN, AM KANTOR, AF DREYFUS, MG FRAUMENI, JF LI, FP TI FOLLOW-UP-STUDY OF 24 FAMILIES WITH LI-FRAUMENI SYNDROME SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; CARCINOMA; SARCOMA; CHILDREN; MOTHERS; TUMORS AB The Li-Fraumeni cancer family syndrome is manifested by susceptibility to breast cancer, sarcomas, and other neoplasms in children and young adults. The present study utilized clinical follow-up data on 545 members of 24 Li-Fraumeni kindreds living and cancer-free at family ascertainment. Two hypotheses were tested based on a model of autosomal dominant genetic predisposition: (a) that syndrome cancers would continue to occur excessively during follow-up compared to the general population, and (b) that the tumors would occur primarily among those family members likely to carry the gene. Population cancer rates were compared with cancer rates in follow-up of the cohort from ascertainment to 1988. Risk of carrying the gene for the syndrome at the time of ascertainment was calculated for each family member under two models with somewhat different definitions of affection with the syndrome. Cancer occurrence after ascertainment was then analyzed according to the risks. Cancer did continue to occur excessively among the entire cohort during follow-up [relative risk (RR 2.1)]. The excess was greatest below age 20 (RR 21.1), declined with increasing age, and was most pronounced for neoplasms featured in the syndrome (RR 18.2). Among persons less than age 45, at least 87% of cancers occurred in those at higher risk of carrying the gene under both genetic models (RR 22.9 and 21.3). The clinical data, therefore, reliably identify individuals likely to carry a dominantly inherited gene conferring susceptibility to a specific constellation of neoplasms. Recent identification of a germ line mutation in the tumor suppressor gene p53 in persons with the syndrome may, if confirmed, have implications for ultimately defining the component tumors of the syndrome and for the causes and prevention of those tumors arising outside these families. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP GARBER, JE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 23 TC 207 Z9 211 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 NOV 15 PY 1991 VL 51 IS 22 BP 6094 EP 6097 PG 4 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100013 PM 1933872 ER PT J AU CARBONE, DP KOROS, AMC LINNOILA, RI JEWETT, P GAZDAR, AF AF CARBONE, DP KOROS, AMC LINNOILA, RI JEWETT, P GAZDAR, AF TI NEURAL CELL-ADHESION MOLECULE EXPRESSION AND MESSENGER-RNA SPLICING PATTERNS IN LUNG-CANCER CELL-LINES ARE CORRELATED WITH NEUROENDOCRINE PHENOTYPE AND GROWTH-MORPHOLOGY SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY HNK-1; NATURAL-KILLER CELLS; L-DOPA DECARBOXYLASE; N-CAM; ENDOCRINE DIFFERENTIATION; NCAM; ANTIGEN; IDENTIFICATION; INVITRO; BINDING AB Diverse histological types of lung cancer express neuroendocrine (NE) markers. We studied the expression and alternative splicing forms of the neural cell adhesion molecule (NCAM) NKH-1, a member of the immunoglobulin superfamily, in 56 lung cancer cell lines representing all histological types. We found a strong correlation between expression of NCAM with both NE phenotype and lack of substrate adhesion in culture. Several cell lines expressed high levels of the leukocyte antigen Leu-7 (HNK-1) but were negative for NCAM antigen and mRNA, indicating that the Leu-7 antigen is distinct from NCAM. All of the NCAM-positive cell lines demonstrate a single 6.2-kilobase mRNA, and analysis of the known 3' alternative splices shows predominant expression of only the membrane form with the small intracytoplasmic domain. We conclude that (a) expression of NCAM is associated with NE phenotype regardless of the histological type of lung cancer; (b) these cell lines share a single form of NCAM; (c) with few exceptions, NCAM expression is associated with cell to cell adhesion and lack of substrate adhesion (growing as floating clusters); and (d) Leu-7 antigen is distinct from NCAM. This form of NCAM may play a functional role in NE differentiation or may be a part of the NE program expressed by these cells. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15261. USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. NR 47 TC 60 Z9 60 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1991 VL 51 IS 22 BP 6142 EP 6149 PG 8 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100021 PM 1718595 ER PT J AU TEMPLETON, NS STETLERSTEVENSON, WG AF TEMPLETON, NS STETLERSTEVENSON, WG TI IDENTIFICATION OF A BASAL PROMOTER FOR THE HUMAN MR 72,000 TYPE-IV COLLAGENASE GENE AND ENHANCED EXPRESSION IN A HIGHLY METASTATIC CELL-LINE SO CANCER RESEARCH LA English DT Note ID HUMAN-TUMOR-CELLS; MAMMALIAN-CELLS; METALLOPROTEINASES; ELEMENT; DNA AB A basal promoter for the M(r) 72,000 type IV collagenase gene was specifically defined by chloramphenicol acetyltransferase assays of a nested set of 5' upstream fragments containing the promoter region. This core promoter is TACATCT and is a noncanonical TATA box that fits the TATA consensus sequence. This sequence begins 26 base pairs in the upstream direction from the start site of transcription for the type IV collagenase gene. This basal promoter is active in the highly metastatic A2058 melanoma cell line. A putative enhancer was found between nucleotides -223 to -422 that produces a 7-fold increase in transcriptional activity in the A2058 melanoma cell line. The region immediately 5' of the basal promoter, upstream to position -422, contains a silencer and represses transcriptional activity in the nonmetastatic HT144 melanoma cell line. The results of this study are consistent with previous data that found high expression of M(r) 72,000 type IV collagenase mRNA and enzymatic activity in the A2058 cell line, whereas low mRNA expression and type IV collagenase activity were found in the HT144 cell line. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 20 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1991 VL 51 IS 22 BP 6190 EP 6193 PG 4 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100029 PM 1657382 ER PT J AU OSBORNE, RJ MERLO, GR MITSUDOMI, T VENESIO, T LISCIA, DS CAPPA, APM CHIBA, I TAKAHASHI, T NAU, MM CALLAHAN, R MINNA, JD AF OSBORNE, RJ MERLO, GR MITSUDOMI, T VENESIO, T LISCIA, DS CAPPA, APM CHIBA, I TAKAHASHI, T NAU, MM CALLAHAN, R MINNA, JD TI MUTATIONS IN THE P53 GENE IN PRIMARY HUMAN BREAST CANCERS SO CANCER RESEARCH LA English DT Note ID TUMOR SUPPRESSOR; POINT MUTATIONS; LUNG-CANCER; ALLELE LOSS; EXPRESSION; HETEROZYGOSITY; CHROMOSOME-17P; CARCINOMA; REGIONS AB Twenty-six primary breast tumors were examined for mutations in the p53 tumor suppressor gene by an RNase protection assay and nucleotide sequence analysis of PCR-amplified p53 complementary DNAs. Each method detected p53 mutations in the same three tumors (12%). One tumor contained two mutations in the same allele. Single strand conformation polymorphism analysis of genomic DNA and complementary DNA proved more sensitive in the detection of mutations. Combining this technique with the other two a total of 1 2 mutations in the p53 gene were demonstrated in 11 tumors (46%), and a polymorphism at codon 213 was detected in another tumor. Loss of heterozygosity on chromosome 17p was detected by Southern blot analysis in 30% of the tumor DNAs. Not all of the tumors containing a point mutation in p53 also had loss of heterozygosity of the remaining allele, suggesting that loss of heterozygosity may represent a later event. C1 USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20892. NCI,ONCOGENET SECT,BETHESDA,MD 20892. OSPED S GIOVANNI VECCHIO,TURIN,ITALY. RI Takahashi, Takashi/I-7262-2014; OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 27 TC 179 Z9 180 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1991 VL 51 IS 22 BP 6194 EP 6198 PG 5 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100030 PM 1682043 ER PT J AU CHOCHUNG, YS AF CHOCHUNG, YS TI 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE INHIBITS THE GROWTH OF CHINESE-HAMSTER OVARY AND MOLT-4 CELLS THROUGH ITS ADENOSINE METABOLITE SO CANCER RESEARCH LA English DT Letter ID CYCLIC-AMP ANALOGS; DIFFERENTIATION; CANCER; LINES RP CHOCHUNG, YS (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1991 VL 51 IS 22 BP 6206 EP 6207 PG 2 WC Oncology SC Oncology GA GP271 UT WOS:A1991GP27100033 PM 1933880 ER PT J AU GRAHAM, C SZPIRER, C LEVAN, G CARPER, D AF GRAHAM, C SZPIRER, C LEVAN, G CARPER, D TI CHARACTERIZATION OF THE ALDOSE REDUCTASE-ENCODING GENE FAMILY IN RAT SO GENE LA English DT Article DE RECOMBINANT DNA; SEQUENCING; PSEUDOGENES; RNASE PROTECTION; CHROMOSOME LOCALIZATION; DIABETIC COMPLICATIONS; POLYOL PATHWAY ID NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; SUPERFAMILY; ELEMENT; ACID; HYBRIDIZATION; RETROPOSONS; PSEUDOGENES; EXPRESSION; INHIBITORS AB Although the enzyme aldose reductase (AR) is implicated in the development of tissue pathology in diabetes, the exact mechanism of this involvement remains unclear. To better understand the role that expression of the aldose reductase-encoding gene (ALR) may play in diabetic complications, we have begun to analyze the gene and its regulatory regions, and we present here the sequence of four ALR genes in the rat. The putative functional gene is 14.1 kb long, has ten exons which show perfect sequence identity to the rat lens AR RNA sequence, and nine introns with classical splice-site consensus sequences. Potential regulatory elements in the 5'-flanking region of this gene include a TATA box and two CCAAT boxes. Probing rat genomic Southern blots with a fragment from the first intron indicates that there is probably only one copy of this gene in the rat genome. The other three genes are processed pseudogenes which show approx. 90% identity to the rat lens AR RNA sequence, contain no introns, and have poly(A) regions at their 3' ends. Chromosomal localization studies show the presence of ALR genes on chromosomes 3, 4 and 6 in the rat with the putative functional gene mapped on chromosome 4. C1 NEI,BLDG 6,RM 232,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV LIBRE BRUXELLES,DEPT BIOL MOLEC,B-1640 RHODE ST GENESE,BELGIUM. GOTHENBURG UNIV,DEPT GENET,S-40033 GOTHENBURG,SWEDEN. NR 42 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1991 VL 107 IS 2 BP 259 EP 267 DI 10.1016/0378-1119(91)90326-7 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA GW140 UT WOS:A1991GW14000011 PM 1748296 ER PT J AU RUMYANTSEVA, GV KENNEDY, CH MASON, RP AF RUMYANTSEVA, GV KENNEDY, CH MASON, RP TI TRACE TRANSITION METAL-CATALYZED REACTIONS IN THE MICROSOMAL METABOLISM OF ALKYL HYDRAZINES TO CARBON-CENTERED FREE-RADICALS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; NADPH-CYTOCHROME-P-450 REDUCTASE; XANTHINE-OXIDASE; HYDROXYL; MECHANISM; OXIDATION; IRON; SUPEROXIDE; ADRIAMYCIN; ETHANOL AB Radical production from alkyl hydrazines (i.e. phenelzine and benzylhydrazine) in rat liver microsomes has been proposed to occur via cytochrome P-450-catalyzed one-electron oxidation followed by beta-scission of an alkyl radical. In microsomes treated with phenelzine (2-phenylethylhydrazine), NADPH, and the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN), the 4-POBN/2-phenylethyl radical adduct was detected by electron paramagnetic resonance spectroscopy. The addition of catalase and superoxide dismutase resulted in a 28.5 and 24% decrease in radical production, respectively. The concentration of the 4-POBN/ 2-phenylethyl radical adduct decreased significantly in the presence of metal chelators, i.e. EDTA, diethylenetriaminepentaacetic acid (DTPA), or deferoxamine mesylate. When phenelzine was incubated with deferoxamine mesylate-washed microsomes and NADPH in Chelex-treated incubation buffer, no significant radical adduct formation was detected. Addition of iron-chelator complexes (either Fe3+-DTPA or Fe3+-EDTA) greatly stimulated production of the 4-POBN/ 2-phenylethyl radical adduct in this system. These results show that the 2-phenylethyl radical produced from phenelzine in a microsomal system arises via a trace transition metal-catalyzed reaction. This reaction may occur through oxidation of phenelzine by the hydroxyl radical, which has also been spin-trapped with 4-POBN in this system. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 28 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21422 EP 21427 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400020 PM 1657966 ER PT J AU GREEN, SM GINSBURG, A LEWIS, MS HENSLEY, P AF GREEN, SM GINSBURG, A LEWIS, MS HENSLEY, P TI ROLES OF METAL-IONS IN THE MAINTENANCE OF THE TERTIARY AND QUATERNARY STRUCTURE OF ARGINASE FROM SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LIVER ARGINASE; DNA-BINDING DOMAIN; COLI ASPARTATE TRANSCARBAMOYLASE; L-ORNITHINE CARBAMOYLTRANSFERASE; SINGLE ZINC FINGER; ESCHERICHIA-COLI; COMPLEX-FORMATION; LIGAND-BINDING; YEAST ADR1; PURIFICATION AB Arginase from Saccharomyces cerevisiae has long been known to be a metal ion-requiring enzyme as it requires heating at 45-degrees-C in the presence of 10 mM Mn2+ for catalytic activation. Metals are also thought to play a structural role in the enzyme, but the identity of the structural metal and its precise structural role have not been defined. Analysis of the metal ions that bind to yeast arginase by atomic absorption spectroscopy reveals that there is a weakly associated Mn2+ that binds to the trimeric enzyme with a stoichiometry of 1.04 +/- 0.05 mol of Mn2+ bound per subunit and an apparent K(D)' value of 26-mu-M at pH 7.0 and 4-degrees-C. A more tightly associated Zn2+ ion can only be removed by dialysis against chelating agents. In occasional preparations, this site contained some Mn2+; however, Zn2+ and Mn2+ together bind to high affinity sites with a stoichiometry of 1.14 +/- 0.25/mol of subunit. Both the loosely associated catalytic Mn2+ ion and the more tightly associated structural Zn2+ ion confer stability to the enzyme. Removal of the weakly bound Mn2+ ion results in a 3-degrees-C decrease in the midpoint of the thermal transition (T1/2) (from 57 by 54-degrees-C) as monitored by UV difference absorption spectroscopy. Removal of the tightly bound Zn2+ ion produces a 19-degrees-C decrease in T1/2 (to 38-degrees-C). Similar results are obtained by circular dichroism measurements. When the Zn2+ ion is removed, the steady-state fluorescence intensity increases 100% as compared to the holoenzyme, with a shift in the emission maximum from 337 to 352 nm. This suggests that in the folded trimeric metalloenzyme, the tryptophan fluorescence is quenched and that upon removal of the structural metal, the quenching is relieved as tryptophan residues become exposed to more polar environments. Equilibrium sedimentation experiments performed after dialysis of the enzyme against EDTA demonstrate that arginase exists in a reversible monomer-trimer equilibrium, in the absence of metal ions, with a K(D) value of 5.05 x 10(-11) M2. In contrast, the native enzyme exists as a trimer with no evidence of dissociation when Mn2+ and Zn2+ are present (Eisenstein, E., Duong, L. T., Ornberg, R. L., Osborne, J. C., Jr., and Hensley, P. (1986) J. Biol. Chem. 261, 12814-12819). In summary, the study presented here demonstrates that binding of a weakly bound Mn2+ ion confers catalytic activity. In contrast, binding of a more tightly associated Zn2+ ion confers substantial stability to the tertiary and quaternary structure of the enzyme. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. NCI,INST HEART LUNG & BLOOD,BIOCHEM LAB,PROT CHEM SECT,BETHESDA,MD 20892. NCI,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 58 TC 46 Z9 47 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21474 EP 21481 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400028 PM 1939179 ER PT J AU AHMED, SA RUVINOV, SB KAYASTHA, AM MILES, EW AF AHMED, SA RUVINOV, SB KAYASTHA, AM MILES, EW TI MECHANISM OF MUTUAL ACTIVATION OF THE TRYPTOPHAN SYNTHASE-ALPHA AND BETA-SUBUNITS - ANALYSIS OF THE REACTION SPECIFICITY AND SUBSTRATE-INDUCED INACTIVATION OF ACTIVE-SITE AND TUNNEL MUTANTS OF THE BETA-SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE O-SULFATE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; TRIOSEPHOSPHATE ISOMERASE; PYRIDOXAL 5'-PHOSPHATE; SUBSTITUTED ALANINES; ABSORPTION-SPECTRA; SCHIFF-BASES; ENZYME; COMPLEX AB The origin of reaction and substrate specificity and the control of activity by protein-protein interaction are investigated using the tryptophan synthase alpha-2-beta-2 complex from Salmonella typhimurium. We have compared some spectroscopic and kinetic properties of the wild type beta-subunit and five mutant forms of the beta-subunit that have altered catalytic properties. These mutant enzymes, which were engineered by site-directed mutagenesis, have single amino acid replacements in either the active site or in the wall of a tunnel that extends from the active site of the a subunit to the active site of the beta-subunit in the alpha-2-beta-2 complex. We find that the mutant alpha-2-beta-2 complexes have altered reaction and substrate specificity in beta-elimination and beta-replacement reactions with L-serine and with beta-chloro-L-alanine. Moreover, the mutant enzymes, unlike the wild type alpha-2-beta-2 complex, undergo irreversible substrate-induced inactivation. The mechanism of inactivation appears to be analogous to that first demonstrated by Metzler's group for inhibition of two other pyridoxal phosphate enzymes. Alkaline treatment of the inactivated enzyme yields apoenzyme and a previously described pyridoxal phosphate derivative. We demonstrate for the first time that enzymatic activity can be recovered by addition of pyridoxal phosphate following alkaline treatment. We conclude that the wild type and mutant alpha-2-beta-2 complexes differ in the way they process the amino acrylate intermediate. We suggest that the wild type beta-subunit undergoes a conformational change upon association with the alpha-subunit that alters the reaction specificity and that the mutant beta-subunits do not undergo the same conformational change upon subunit association. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, RM 2A09, BETHESDA, MD 20892 USA. NR 59 TC 35 Z9 35 U1 1 U2 5 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 NOV 15 PY 1991 VL 266 IS 32 BP 21548 EP 21557 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400038 PM 1939184 ER PT J AU BODENNER, DL MROCZYNSKI, MA WEINTRAUB, BD RADOVICK, S WONDISFORD, FE AF BODENNER, DL MROCZYNSKI, MA WEINTRAUB, BD RADOVICK, S WONDISFORD, FE TI A DETAILED FUNCTIONAL AND STRUCTURAL-ANALYSIS OF A MAJOR THYROID-HORMONE INHIBITORY ELEMENT IN THE HUMAN THYROTROPIN BETA-SUBUNIT GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPONSE ELEMENTS; RECEPTOR; BINDING; EXPRESSION; PROMOTER; MEDIATE; DOMAIN; SITE; JUN AB The first exon of the human thyrotropin-beta (hTSH-beta) gene has been demonstrated in our laboratory to contain a major thyroid hormone inhibitory element. In order to characterize fully this element, we have performed a detailed functional and structural scanning mutational analysis of this element. Various -1192 to +37 (base pairs) bp fragments of the hTSH-beta-gene containing consecutive five deoxythymidine substitution mutations of the first exon were inserted into a luciferase reporter plasmid and transiently transfected into human embryonal cells (293) and stably transfected into rat pituitary cells (GH3). Two domains (domain 1 and 2) were identified by scanning mutations that were essential for function of the thyroid hormone inhibitory element: +3 to +13 bp and +28 to +37 bp. Biotinylated DNA fragments containing -12 to +43 bp of the hTSH-beta-gene and the identical scanning mutations demonstrate that in vitro synthesized c-erbA-beta-binding is disrupted as much as 95% by mutations from -3 to +17 bp and to a lesser extent (20-30%) by mutations from +23 to +27 bp and from +33 to +43 bp. Domain 1 displayed a higher affinity for c-erbA-beta than domain 2 in avidin-biotin complex DNA-binding and gel-mobility assays. Using increasing amounts of in vitro synthesized c-erbA-beta, we were unable to demonstrate more than one protein-DNA complex in gel-mobility assays. However, using the avidin-biotin complex DNA-binding assay and the cross-linking reagent, 1,6-bismaleimidohexane, we were able to demonstrate thyroid hormone receptor dimer formation on domain 1 but not to any significant extent on domain 2. In conclusion, functional and DNA-binding studies suggest that the thyroid hormone receptor binds to two distinct regions in the first exon of the hTSH-beta gene. The upstream site (domain 1) binds c-erbA-beta with higher affinity and is capable of binding c-erbA-beta as a dimer under some conditions, while the downstream site (domain 2) appears to bind a single molecule of c-erbA-beta with lower affinity. These results suggest that thyroid hormone receptor, binding to at least two sites in the first exon, act in conjunction to mediate T3 inhibition of hTSH-beta expression. C1 UNIV HOSP CLEVELAND,DIV PEDIAT,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,DIV ADULT ENDOCRINOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. RP BODENNER, DL (reprint author), NIDDKD,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 32 TC 79 Z9 80 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21666 EP 21673 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400053 PM 1657975 ER PT J AU SAMUDZI, CT BURTON, LE RUBIN, JR AF SAMUDZI, CT BURTON, LE RUBIN, JR TI CRYSTAL-STRUCTURE OF RECOMBINANT RABBIT INTERFERON-GAMMA AT 2.7-A RESOLUTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN IMMUNE INTERFERON; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; HUMAN ALPHA; BETA; LYMPHOTOXIN; PROTEINS; CELLS; MOTIF AB The crystal structure of recombinant rabbit interferon-gamma was solved by the multiple isomorphous replacement technique at 2.7-angstrom resolution and refined to a crystallographic R-factor of 26.2%. The interferon crystallizes with one-half of the functional dimer in the asymmetric unit, with the two polypeptide chains of the dimer related by a crystallographic 2-fold symmetry axis. The structure is predominantly alpha-helical with extensive interdigitation of the alpha-helical segments of the two polypeptide chains. C1 GENENTECH INC,DEPT PROC DEV,SAN FRANCISCO,CA 94080. RP SAMUDZI, CT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 31 TC 63 Z9 64 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21791 EP 21797 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400071 PM 1939201 ER PT J AU BILL, CA GROCHAN, BM MEYN, RE BOHR, VA TOFILON, PJ AF BILL, CA GROCHAN, BM MEYN, RE BOHR, VA TOFILON, PJ TI LOSS OF INTRAGENOMIC DNA-REPAIR HETEROGENEITY WITH CELLULAR-DIFFERENTIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLEMENTATION GROUP-C; HAMSTER OVARY CELLS; BETA-ACTIN GENE; ULTRAVIOLET-IRRADIATION; MURINE PROADIPOCYTES; LIPOPROTEIN-LIPASE; PYRIMIDINE DIMERS; GROWTH ARREST; MUSCLE-CELLS; DHFR GENE AB The influence of terminal differentiation on UV-induced DNA damage and its repair in transcriptionally active and inactive genomic sequences was investigated using the murine 3T3-T proadipocyte cell culture system. Actively cycling 3T3-T cells terminally differentiate into adipocytes after exposure to media containing platelet-depleted human plasma. Suitable DNA fragments were analyzed from four genes: beta-actin, adenosine deaminase, dihydrofolate reductase, and lipoprotein lipase. As a result of 3T3-T cell differentiation, lipoprotein lipase and beta-actin expression was modified, whereas adenosine deaminase and dihydrofolate reductase expression was not affected. A DNA fragment representing the transcriptionally inactive locus 70-38 was also evaluated. UV-induced cyclobutane pyrimidine dimers, detected as UV-specific endonuclease-sensitive sites, in each fragment increased linearly as a function of UV dose (0-20 J/m2) independently of gene expression or differentiation. Sequence-specific repair of dimers was measured in stem and terminally differentiated 3T3-T cells after UV irradiation (10 J/m2). For undifferentiated stem cells, the rate and extent of dimer repair was higher in the actively transcribed adenosine deaminase and dihydrofolate reductase genes than in the inactive lipoprotein lipase or 70-38 fragments, the greater difference being observed in the first 8 h post-UV irradiation. In contrast, similar dimer repair rates were found for each DNA fragment in terminally differentiated 3T3-T cells. These data suggest that cellular differentiation is accompanied by a loss of heterogeneity in intragenomic DNA repair. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL RADIOTHERAPY,HOUSTON,TX 77030. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA50207] NR 43 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21821 EP 21826 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400076 PM 1939206 ER PT J AU LIU, YH TENG, CT AF LIU, YH TENG, CT TI CHARACTERIZATION OF ESTROGEN-RESPONSIVE MOUSE LACTOFERRIN PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LACTOTRANSFERRIN GENE; NUCLEOTIDE-SEQUENCE; CHROMOSOMAL LOCALIZATION; HUMAN TRANSFERRIN; MAMMARY-GLAND; EXPRESSION; TRANSCRIPTION; CDNA; ELEMENTS; CELLS AB Mouse lactoferrin is expressed in a variety of tissues under different types of control. To understand how molecular mechanisms govern the mode of lactoferrin expression, we isolated and characterized the 5'-flanking region of the lactoferrin gene. Several clones containing lactoferrin gene fragments were isolated from a mouse (129/J) genomic library including clone lambda-J14, which contains a 7.5-kilobase pair 5'-flanking sequence. Sequence analysis of the region flanking the transcription initiation site revealed the following: a TATA-like sequence, two CAAT boxes, three GC boxes including one within the first intron, an AP2 site, seven PU boxes, an AC-rich region, a B1 sequence, and an estrogen-responsive element consensus sequence overlapping with a chicken ovalbumin upstream promoter-binding element. Footprinting analysis demonstrated that several regions, including the putative estrogen-responsive element region, in the 5'-flanking sequence were protected from DNase I digestion. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. The mouse lactoferrin gene promoter was active in human endometrium carcinoma RL 95-2 cells and in rat glioma C6 cells. Multiple upstream elements modulated the basal transcriptional promoter activity. The transcription level directed by this minimal promoter was controlled by both positive (between -1739 and -922) and negative (between -2644 and -1739, and between -589 and -291) regulatory sequences. A tissue-specific regulatory sequence was critical for the establishment of lactoferrin expression in human endometrium carcinoma cells, but not in rat glioma cells located between -1739 and -922. Reporter plasmid 0.6 mL14-CAT, containing the estrogen-responsive element sequence, was estrogen-responsive in the presence of estrogen receptor in human endometrium carcinoma RL 95-2 cells. C1 NIEHS,REPROD & DEV TOXICOL,DEV ENDOCRINOL & PHARMACOL SECT,RES TRIANGLE PK,NC 27709. NR 39 TC 75 Z9 76 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 21880 EP 21885 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400084 PM 1939212 ER PT J AU HURWITZ, DR EMANUEL, SL NATHAN, MH SARVER, N ULLRICH, A FELDER, S LAX, I SCHLESSINGER, J AF HURWITZ, DR EMANUEL, SL NATHAN, MH SARVER, N ULLRICH, A FELDER, S LAX, I SCHLESSINGER, J TI EGF INDUCES INCREASED LIGAND-BINDING AFFINITY AND DIMERIZATION OF SOLUBLE EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR EXTRACELLULAR DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; BACULOVIRUS EXPRESSION VECTOR; INSECT CELLS; SIGNAL TRANSDUCTION; ALLOSTERIC ACTIVATION; SELF-PHOSPHORYLATION; POINT MUTATION; PROTEIN-KINASE; CROSS-LINKING; SITE AB The binding of epidermal growth factor (EGF) to its cell surface receptor (EGF-R) results in a number of intracellular responses including the activation of the receptor intracellular tyrosine kinase. Receptor oligomerization induced by ligand binding has been suggested to play an important role in signal transduction. However, the mechanisms involved in oligomerization and signal transduction are poorly understood. We have produced and purified several milligrams of recombinant extracellular domain of the EGF receptor (EGF-Rx) using the baculovirus/insect cell expression system. The baculovirus-generated EGF-Rx is glycosylated, has had its signal peptide correctly cleaved, and exhibits a dissociation constant for EGF similar to that for solubilized full-length receptor, of about 100 nM. The binding of EGF to EGF-Rx leads to the formation of receptor dimers and higher oligomerization states which are irreversibly captured using the covalent cross-linking agent disuccinimidyl suberate. Interestingly, purified receptor monomers and dimers, stabilized by the cross-linker in the presence of EGF, exhibit increased binding affinity toward EGF as compared with receptor monomers which have not been exposed to EGF. It appears that the high affinity state of receptor can be maintained by the covalent crosslinking agent. These results indicate that in addition to ligand binding, the extracellular domain of EGF receptor possesses the inherent ability to undergo ligand-induced dimerization and that the low affinity state is converted to a high affinity state by EGF. C1 NIAID,DIV AIDS,DEV THERAPEUT BRANCH,ROCKVILLE,MD 20892. MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY. NYU MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. RP HURWITZ, DR (reprint author), RHONE POULENC RORER CENT RES,KING OF PRUSSIA,PA 19406, USA. NR 43 TC 103 Z9 103 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1991 VL 266 IS 32 BP 22035 EP 22043 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GP804 UT WOS:A1991GP80400106 PM 1657987 ER PT J AU KOH, S HIGGINS, GA AF KOH, S HIGGINS, GA TI DIFFERENTIAL REGULATION OF THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR DURING POSTNATAL-DEVELOPMENT OF THE RAT-BRAIN SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE INSITU HYBRIDIZATION; ACETYLCHOLINE; CEREBELLUM; BRAIN-STEM; BASAL FOREBRAIN ID CHOLINERGIC NEURONAL HYPERTROPHY; MESSENGER-RNA; NEUROTROPHIC FACTOR; MOLECULAR-CLONING; ADULT-RAT; REGIONAL EXPRESSION; GENE-EXPRESSION; BASAL FOREBRAIN; FACTOR FAMILY; SPINAL-CORD AB We studied the temporal and spatial localization of the low-affinity nerve growth factor receptor (LNGF-R) during the early postnatal period in rat brain in order to understand better the relationship between nerve growth factor (NGF)-like responsiveness and the development of specific central neuronal populations. Four different developmental patterns of LNGF-R mRNA hybridization were found in this study. First, some neurons contain high levels of LNGF-R mRNA from postnatal time points into adulthood, as exemplified by neurons of the cholinergic basal forebrain and mesencephalic trigeminal nucleus. Second, several cell groups exhibit robust hybridization during the early postnatal period but contain much reduced levels of LNGF-R mRNA in the adult brain. These include striatal neurons, Purkinje cells of the cerebellum, and several medullary nuclei. A third group of cells produces the LNGF-R transiently during development, including cranial nerve nuclei of the brainstem, the periolivary nuclei complex, the reticular formation, and the deep cerebellar nuclei. Finally, cell populations which may exist only transiently during central nervous system (CNS) development, such as subplate neurons of the cerebral cortex, appear to express the LNGF-R during only a brief period. These results show that the LNGF-R gene is differentially regulated in a cell type-specific manner during development, and suggests that diverse neuronal populations require only transient growth factor sensitivity, while others exhibit NGF-like responsitivity into maturity. C1 NIA,MOLEC NEUROBIOL SECT,BIOL CHEM LAB,GERONTOL RES CTR,BALTIMORE,MD 21224. RP KOH, S (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14642, USA. FU NIA NIH HHS [AG T320107]; NINDS NIH HHS [NS 26845] NR 48 TC 70 Z9 70 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 15 PY 1991 VL 313 IS 3 BP 494 EP 508 DI 10.1002/cne.903130310 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA GQ850 UT WOS:A1991GQ85000009 PM 1663136 ER PT J AU JANSEN, R DAMIA, G USUI, N KELLER, J FUTAMI, H GOEY, H BACK, TT LONGO, DL RUSCETTI, FW WILTROUT, RH AF JANSEN, R DAMIA, G USUI, N KELLER, J FUTAMI, H GOEY, H BACK, TT LONGO, DL RUSCETTI, FW WILTROUT, RH TI EFFECTS OF RECOMBINANT TRANSFORMING GROWTH FACTOR-BETA-1 ON HEMATOLOGIC RECOVERY AFTER TREATMENT OF MICE WITH 5-FLUOROURACIL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-BETA; CELL PROLIFERATION; INHIBITION; ALPHA; SERUM AB Transforming growth factor, beta-1 (TGF-beta-1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-beta might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-beta-1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-beta-1 were administered systemical immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-beta-1 was administered at daily doses of greater-than-or-equal-to 5-mu-g/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-beta-1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BLDG 560,RM 31-93,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 21 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1991 VL 147 IS 10 BP 3342 EP 3347 PG 6 WC Immunology SC Immunology GA GQ171 UT WOS:A1991GQ17100014 PM 1940339 ER PT J AU MANGAN, DF WAHL, SM AF MANGAN, DF WAHL, SM TI DIFFERENTIAL REGULATION OF HUMAN MONOCYTE PROGRAMMED CELL-DEATH (APOPTOSIS) BY CHEMOTACTIC FACTORS AND PRO-INFLAMMATORY CYTOKINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; GENE-EXPRESSION; INTERLEUKIN-1; INDUCTION; GAMMA; PHAGOCYTOSIS; MACROPHAGES; PEPTIDES; SURVIVAL; INVITRO AB In the absence of appropriate stimuli, monocytes undergo programmed cell death (PCD) or apoptosis. IL-1-beta and TNF-alpha prevent monocyte PCD, which suggests that viability may be regulated by biologically active peptides released during inflammation. To explore this possibility, we evaluated several chemotactic factors and pro-inflammatory cytokines for their ability to regulate PCD. The recruitment factors, FMLP, C fragment C5a, monocyte chemotactic protein-1, or transforming growth factor-beta-1, were incapable of rescuing monocytes from PCD nor did they enhance PCD, whereas several inflammatory cytokines in addition to IL-1-beta and TNF-alpha, including granulocyte-monocyte-CSF and IFN-gamma, prevented monocyte PCD provided that sufficient levels of these cytokines were continuously maintained in the cultures. Cytokine-mediated inhibition of PCD could be blocked by specific antisera, ruling out potential effects caused by LPS contamination. When tested at equivalent concentrations, IL-2, IL-4, and IL-6 had no effect on PCD indicating selectivity in cytokine modulation of monocyte PCD. Because monocytes produce IL-1-beta, TNF-alpha, and granulocyte-monocyte CSF when activated, the data suggest autocrine as well as paracrine control of cell survival and accumulation. The results also suggest that monocytes recruited to a site of inflammation will undergo PCD in the absence of specific cytokines and/or other stimuli that block this process. RP MANGAN, DF (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,ROOM 329,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [DE05576] NR 31 TC 262 Z9 265 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1991 VL 147 IS 10 BP 3408 EP 3412 PG 5 WC Immunology SC Immunology GA GQ171 UT WOS:A1991GQ17100023 PM 1940344 ER PT J AU BRORSON, KA BEVERLY, B KANG, SM LENARDO, M SCHWARTZ, RH AF BRORSON, KA BEVERLY, B KANG, SM LENARDO, M SCHWARTZ, RH TI TRANSCRIPTIONAL REGULATION OF CYTOKINE GENES IN NONTRANSFORMED T-CELLS - APPARENT CONSTITUTIVE SIGNALS IN RUN-ON ASSAYS CAN BE CAUSED BY REPEAT SEQUENCES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; LYMPHOKINE MESSENGER-RNA; INTERLEUKIN-2 GENE; LYMPHOCYTES-T; MURINE INTERLEUKIN-2; NUCLEOTIDE-SEQUENCE; CYCLOSPORIN-A; RIBOSOMAL-RNA; EXPRESSION AB Cytokines are immunoregulatory proteins that are secreted by T lymphocytes and other cells upon activation. A controversy exists as to whether the induction of cytokine production is mediated at the transcriptional level by the initiation of RNA synthesis or at the post-transcriptional level by the enhancement of mRNA stability. We show that in a nontransformed T cell clone the induction of all of the cytokines that are analyzed in this report is mediated transcriptionally. We also found that a constitutive signal was seen in resting cells when the probes used in the nuclear run-on assay contained some potential cross-hybridizing sequences, for example a poly (A) tract in a cDNA probe. This observation could explain the constitutive signals seen in other studies that claim cytokine production is regulated by differential mRNA stability. C1 NIAID,INST IMMUNOL,BETHESDA,MD 20892. RP BRORSON, KA (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 52 TC 66 Z9 66 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1991 VL 147 IS 10 BP 3601 EP 3609 PG 9 WC Immunology SC Immunology GA GQ171 UT WOS:A1991GQ17100051 PM 1940359 ER PT J AU BYRD, LG MCDONALD, AH GOLD, LG POTTER, M AF BYRD, LG MCDONALD, AH GOLD, LG POTTER, M TI SPECIFIC PATHOGEN-FREE BALB/CAN MICE ARE REFRACTORY TO PLASMACYTOMA INDUCTION BY PRISTANE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GERM-FREE; SUSCEPTIBILITY AB Forty to sixty percent of conventionally (CON) raised BALB/cAnPt (BALB/c) mice develop plasmacytomas (PCT) when injected with three 0.5 ml i.p. injections of pristane. When CON-BALB/c mice were converted to specific pathogen free (SPF) status by foster nursing caesarean delivered term mice on C3H/HeN SPF mothers and maintained under strict SPF conditions, < 5 % of the mice developed pristane-induced PCT. FACS analysis of the cellular composition of oil granulomatous tissue revealed a dramatic influx of CD4+ cells in CON mice that was significantly reduced in SPF mice. Moreover, while both CON and SPF mice had similar patterns of gut flora colonization, only CON-BALB/c mice had occasional circulating antibodies to mouse hepatitis virus and Sendai viruses. Maintenance in strict SPF conditions, therefore, results in a prolonged state of relative Ag deprivation and a failure to continuously activate new T and B cell populations. The results suggest that PCT formation depends on exogenous antigenic stimulation and that the presence of minimal gut flora is insufficient to render these mice susceptible to PCT induction. C1 HAZLETON LABS AMERICA INC,ROCKVILLE,MD 20850. RP BYRD, LG (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B21,BETHESDA,MD 20892, USA. NR 20 TC 51 Z9 51 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1991 VL 147 IS 10 BP 3632 EP 3637 PG 6 WC Immunology SC Immunology GA GQ171 UT WOS:A1991GQ17100055 PM 1682379 ER PT J AU REDEGELD, F FILIPPINI, A SITKOVSKY, M AF REDEGELD, F FILIPPINI, A SITKOVSKY, M TI COMPARATIVE-STUDIES OF THE CYTOTOXIC LYMPHOCYTE-T-MEDIATED CYTOTOXICITY AND OF EXTRACELLULAR ATP-INDUCED CELL-LYSIS - DIFFERENT REQUIREMENTS IN EXTRACELLULAR MG2+ AND PH SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTI-RECEPTOR ANTIBODY; CYTOLYTIC LYMPHOCYTES; SERINE ESTERASE; TARGET-CELLS; MOUSE LYMPHOCYTES; PROTEIN-KINASE; ACTIVATION; EXOCYTOSIS; ATTACHMENT; SECRETION AB We recently proposed that extracellular ATP (ATP(o)) may be involved in CTL-mediated cytotoxicity by acting in concert with yet unidentified cellular components (ATP(o) receptors/ATP(o)-binding proteins, ectoprotein kinases). The TCR-triggered ATP(o) accumulation by CTL has been demonstrated, whereas the resistance of CTL to ATP. was explained by the action of highly active ecto-ATPases or by the absence of relevant ATP-binding proteins. However, no data were available to discriminate between the possibilities of: i) ATP(o) acting alone as a 'hit" molecule because of the cell-permeabilizing properties of ATp4- or ii) ATP(o) acting as a "messenger" (as MgATP2-) in concert with other molecules. Comparing ATP(o)-induced and CTL-mediated cell lysis, we found that ATP(o)-induced lysis of some target cells is greatly decreased at neutral and acidic pH. whereas Ca2+-dependent CTL-mediated lysis of the same cells is barely affected. In agreement with the observed pH dependency, at low Mg2+ concentrations, which favor ATP4- over MgATP2-, maximal ATP(o)-induced lysis was observed. However, CTL-mediated cytotoxicity in both Ag-specific and retargeting assays was markedly reduced at low Mg2+ concentrations. These results suggest that ATP(o) acting alone as a 'hit" molecule cannot fully account for the extracellular Ca2+-dependent lethal hit delivery by CTL or that ATP4- is active at very low concentrations. This conclusion was further supported by studying the lytic effect of ATP(o) and CTL on the anti-TCR mAb-coupled SRBC. CTL were efficient in the SRBC lysis, whereas no lysis of SRBC by ATP. was detected. The resistance of SRBC to ATP(o) is not caused by a high ATP(o) degradation, because the ecto-ATPase activity of SRBC was much lower than in ATP(o)-resistant CTL OE4 cells and comparable with EL4 tumor cells, which were easily lysed by ATP(o). These data suggested the need for careful consideration of the pH and cation composition of the media used for studying ATP(o) effects. The caveats in the use of ATP-degrading enzymes to implicate the role of extracellular ATP(o) in the CTL-mediated cytotoxicity are described here. A clarification of the previously described cytotoxicity inhibition by hexokinase, which is caused by an inhibitory salt effect, is presented. It is suggested that if Ca2+-dependent lysis of SRBC and of other target cells by CTL does involve extracellular ATP, it may function as a "messenger" in concert with other extracellular molecules. The obtained data also implicate extracellular Mg2+ in a step other than the accessory molecules-dependent conjugate formation and prompt further studies of MgATp2- utilizing ectoprotein kinases and their substrates. C1 NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,BETHESDA,MD 20892. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 41 TC 50 Z9 51 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1991 VL 147 IS 10 BP 3638 EP 3645 PG 8 WC Immunology SC Immunology GA GQ171 UT WOS:A1991GQ17100056 PM 1940362 ER PT J AU ARAUJO, M HAVLIN, S STANLEY, HE AF ARAUJO, M HAVLIN, S STANLEY, HE TI ANOMALOUS FLUCTUATIONS IN TRACER CONCENTRATION IN STRATIFIED MEDIA WITH RANDOM VELOCITY-FIELDS SO PHYSICAL REVIEW A LA English DT Note ID RANDOM-WALKS; ENHANCED DIFFUSION; SOLUTE TRANSPORT; SUPERDIFFUSION AB We find a quantitative law that describes the nature of the anomalous fluctuations in tracer concentration when diffusion occurs in a stratified medium, with drift velocities which are constant in the x direction, but vary randomly from layer to layer in the y direction. We find that the fluctuations of the tracer concentration P = P(x,t) are described by an extremely broad histogram of the form n(log10P) approximately A/(log10P)3exp[-B/(log10P)2]. Moreover, the relative fluctuations delta-P increase exponentially with x. Our results are supported by numerical calculations based on the method of exact enumeration. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. INTEVEP SA,SECC FIS ROCAS,CARACAS 1070A,VENEZUELA. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP ARAUJO, M (reprint author), BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215, USA. NR 16 TC 5 Z9 5 U1 1 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD NOV 15 PY 1991 VL 44 IS 10 BP 6913 EP 6915 DI 10.1103/PhysRevA.44.6913 PG 3 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA GR738 UT WOS:A1991GR73800079 ER PT J AU WINK, DA KASPRZAK, KS MARAGOS, CM ELESPURU, RK MISRA, M DUNAMS, TM CEBULA, TA KOCH, WH ANDREWS, AW ALLEN, JS KEEFER, LK AF WINK, DA KASPRZAK, KS MARAGOS, CM ELESPURU, RK MISRA, M DUNAMS, TM CEBULA, TA KOCH, WH ANDREWS, AW ALLEN, JS KEEFER, LK TI DNA DEAMINATING ABILITY AND GENOTOXICITY OF NITRIC-OXIDE AND ITS PROGENITORS SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI; POINT MUTATIONS; 5-METHYLCYTOSINE; MACROPHAGES; NITROSATION; ACTIVATION; RATS; HYPOMETHYLATION; NUCLEOTIDES; CYTOSINE AB Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were > 99% C --> T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS NATL LAB,FREDERICK,MD 21701. US FDA,ROCKVILLE,MD 20852. GLAXO INC,RES TRIANGLE PK,NC 27709. US FDA,WASHINGTON,DC 20204. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21701. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74102] NR 47 TC 992 Z9 1008 U1 4 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 15 PY 1991 VL 254 IS 5034 BP 1001 EP 1003 DI 10.1126/science.1948068 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP883 UT WOS:A1991GP88300043 PM 1948068 ER PT J AU HYAMS, KC BOURGEOIS, AL MERRELL, BR ROZMAJZL, P ESCAMILLA, J THORNTON, SA WASSERMAN, GM BURKE, A ECHEVERRIA, P GREEN, KY KAPIKIAN, AZ WOODY, JN AF HYAMS, KC BOURGEOIS, AL MERRELL, BR ROZMAJZL, P ESCAMILLA, J THORNTON, SA WASSERMAN, GM BURKE, A ECHEVERRIA, P GREEN, KY KAPIKIAN, AZ WOODY, JN TI DIARRHEAL DISEASE DURING OPERATION-DESERT-SHIELD SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TOXIGENIC ESCHERICHIA-COLI; TRAVELERS DIARRHEA; NORWALK VIRUS; SOUTH-KOREA; TRIMETHOPRIM; SHIGELLA; ANTIGEN; SULFAMETHOXAZOLE; GASTROENTERITIS; CHILDREN AB Background. Under combat conditions infectious disease can become a major threat to military forces. During Operation Desert Shield, there were numerous outbreaks of diarrhea among the U.S. forces. To evaluate the causes of and risk factors for diarrheal disease, we collected clinical and epidemiologic data from U.S. troops stationed in northeastern Saudi Arabia. Methods. Between September and December 1990, stool cultures for enteric pathogens were obtained from 432 military personnel who presented with diarrhea, cramps, vomiting, or hematochezia. In addition, a questionnaire was administered to 2022 soldiers in U.S. military units located in various regions of Saudi Arabia. Results. A bacterial enteric pathogen was identified in 49.5 percent of the troops with gastroenteritis. Enterotoxigenic Escherichia coli and Shigella sonnei were the most common bacterial pathogens. Of 125 E. coli infections, 39 percent were resistant to trimethoprim-sulfamethoxazole, 63 percent to tetracycline, and 48 percent to ampicillin. Of 113 shigella infections, 85 percent were resistant to trimethoprim-sulfamethoxazole, 68 percent to tetracycline, and 21 percent to ampicillin. All bacterial isolates were sensitive to norfloxacin and ciprofloxacin. After an average of two months in Saudi Arabia, 57 percent of the surveyed troops had at least one episode of diarrhea, and 20 percent reported that they were temporarily unable to carry out their duties because of diarrheal symptoms. Vomiting was infrequently reported as a primary symptom, but of 11 military personnel in whom vomiting was a major symptom, 9 (82 percent) had serologic evidence of infection with the Norwalk virus. Conclusions. Gastroenteritis caused by enterotoxigenic E coli and shigella resistant to a number of drugs was a major problem that frequently interfered with the duties of U.S. troops during Operation Desert Shield. C1 ARMED FORCES RES INST MED SCI,BANGKOK,THAILAND. NIH,INFECT DIS LAB,BETHESDA,MD 20892. USN,MED RES & DEV COMMAND,BETHESDA,MD 20814. USN,MED RES INST DETACHMENT,LIMA,PERU. USN,ENVIRONM & PREVENT MED UNIT 7,NAPLES,ITALY. USA,MED DEPT ACT,PREVENT MED SERV,FT CAMPBELL,KY. USN,MED RES UNIT 3,DIV EPIDEMIOL,CAIRO,EGYPT. WILLIAM BEAUMONT ARMY MED CTR,DEPT PEDIAT,EL PASO,TX 79920. RP HYAMS, KC (reprint author), USN,MED RES INST,DIV EPIDEMIOL,12300 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 47 TC 193 Z9 201 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 14 PY 1991 VL 325 IS 20 BP 1423 EP 1428 DI 10.1056/NEJM199111143252006 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GP524 UT WOS:A1991GP52400006 PM 1656260 ER PT J AU WALSH, TJ PIZZO, PA AF WALSH, TJ PIZZO, PA TI CIRCULATING CANDIDA ENOLASE IN INVASIVE CANDIDIASIS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SYSTEMIC CANDIDIASIS; CYTOPLASMIC ANTIGEN; ALBICANS; SERA; IDENTIFICATION; DIAGNOSIS; ASSAY RP WALSH, TJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 14 PY 1991 VL 325 IS 20 BP 1446 EP 1447 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GP524 UT WOS:A1991GP52400021 ER PT J AU WASHINGTON, AE CATES, W WASSERHEIT, JN AF WASHINGTON, AE CATES, W WASSERHEIT, JN TI PREVENTING PELVIC INFLAMMATORY DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; CHLAMYDIA-TRACHOMATIS INFECTION; ORAL-CONTRACEPTIVE USE; ADOLESCENT SEXUALITY; COST-EFFECTIVENESS; CLINICAL-TRIAL; BARRIER-METHOD; UNITED-STATES; PRIMARY CARE; RISK AB Effective strategies for preventing pelvic inflammatory disease (PID) are crucial to protect women from adverse reproductive consequences and to avoid substantial economic losses. To identify current PID prevention options and assess their efficacy, we conducted a literature search and examined relevant data in published reports. We organized our review by level of participation (ie, individuals, providers, and communities) and prevention (ie, primary, secondary, and tertiary). For individuals, several prevention strategies related to personal protection appear promising, but few have been appropriately evaluated. For providers of health care, five prevention measures are recommended, including such primary prevention activities as counseling and patient education in addition to the usual diagnosis and treatment. Specific evidence supporting the efficacy of these provider practices, however, is limited. For communities, maintaining comprehensive sexually transmitted disease control strategies to prevent lower genital tract chlamydial and gonococcal infection is most important in reducing both symptomatic and asymptomatic PID. We provide specific recommendations for preventing PID and outline research needs. C1 CTR DIS CONTROL,CTR PREVENT SERV,DIV SEXUALLY TRANSMITTED DIS HIV PREVENT,ATLANTA,GA 30333. NIAID,SEXUALLY TRANSMITTED DIS BRANCH,BETHESDA,MD 20892. RP WASHINGTON, AE (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,CTR REPROD HLTH POLICY RES,1388 SUTTER ST,11TH FLOOR,SAN FRANCISCO,CA 94109, USA. FU NIAID NIH HHS [AI24768]; PHS HHS [282-88-0018] NR 75 TC 30 Z9 30 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 13 PY 1991 VL 266 IS 18 BP 2574 EP 2580 DI 10.1001/jama.266.18.2574 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GN660 UT WOS:A1991GN66000034 PM 1942403 ER PT J AU RAO, CT PITHA, J AF RAO, CT PITHA, J TI REACTIVITIES AT THE O-2, O-3, AND O-6 POSITIONS OF CYCLOAMYLOSES IN HAKOMORI METHYLATION SO CARBOHYDRATE RESEARCH LA English DT Note ID CYCLOMALTO-OLIGOSACCHARIDES; NMR-SPECTRA; CYCLODEXTRINS; ASSIGNMENT RP RAO, CT (reprint author), NIA,GRC,BALTIMORE,MD 21224, USA. NR 15 TC 15 Z9 15 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 11 PY 1991 VL 220 BP 209 EP 213 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GT080 UT WOS:A1991GT08000018 ER PT J AU LAI, GM MOSCOW, JA ALVAREZ, MG FOJO, AT BATES, SE AF LAI, GM MOSCOW, JA ALVAREZ, MG FOJO, AT BATES, SE TI CONTRIBUTION OF GLUTATHIONE AND GLUTATHIONE-DEPENDENT ENZYMES IN THE REVERSAL OF ADRIAMYCIN RESISTANCE IN COLON-CARCINOMA CELL-LINES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER-CELLS; S-TRANSFERASE-PI; DOXORUBICIN CYTO-TOXICITY; BUTHIONINE SULFOXIMINE; MULTIDRUG-RESISTANCE; TUMOR-CELLS; DRUG-RESISTANCE; PROTECTIVE ROLE; REDOX CYCLE; EXPRESSION AB Four human colon cancer cell lines (SW620, LS 180, DLD-1, and HCT-15) and sub-lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P-glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD-1 and HCT-15 and their drug-resistant derivatives, there was no relation between the effect of the glutathione-depleting agent BSO, the mRNA expression of both selenium-dependent glutathione peroxidase (GPx) and glutathione S-transferase pi (GST-pi), bulk glutathione S-transferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub-lines, which do not principally rely on P-glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin-resistant subline (LS 180 Ad150) after short-term drug exposure. Furthermore, the LS 180 Ad 150 cells demonstrated an increase in both GPx and GST-pi mRNA expression. These observations suggest that glutathione-mediated detoxification of Adriamycin may play a role in the resistance of this sub-line. Verapamil enhanced Adriamycin cytotoxicity 1.2- to 12-fold in the intrinsically resistant cells and as much as 15-fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug-resistance-modulating agents in the treatment of colon carcinoma. C1 NCI,MED BRANCH,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 34 TC 60 Z9 61 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1991 VL 49 IS 5 BP 688 EP 695 DI 10.1002/ijc.2910490511 PG 8 WC Oncology SC Oncology GA GP783 UT WOS:A1991GP78300010 PM 1682279 ER PT J AU LAI, GM CHEN, YN MICKLEY, LA FOJO, AT BATES, SE AF LAI, GM CHEN, YN MICKLEY, LA FOJO, AT BATES, SE TI P-GLYCOPROTEIN EXPRESSION AND SCHEDULE DEPENDENCE OF ADRIAMYCIN CYTOTOXICITY IN HUMAN COLON-CARCINOMA CELL-LINES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MULTIDRUG-RESISTANCE; OVARIAN-CANCER; MEMBRANE-VESICLES; GENE; PERMEABILITY; COLCHICINE; LIVER AB Four human colon cancer cell lines (SW620, LS 180, DLD-1, and HCT-15) and Adriamycin-resistant sub-lines with varying degrees of P-glycoprotein expression were studied to evaluate the reversibility of Adriamycin resistance in human colon cancer. Two groups of cell lines were studied. In the first, including a series of Adriamycin-resistant SW620 and DLD-1 sub-lines, and in parental HCT-15 cells, P-glycoprotein has a major role in Adriamycin resistance, as evidenced by a correlation between Adriamycin resistance, expression of the multidrug-resistance gene mdr-1 and its product, P-glycoprotein (Pgp), decreased drug accumulation and reversibility by verapamil. In these cell lines, increasing doses of verapamil are required to fully reverse increasing levels of resistance. In the second group, including parental SW620, DLD-1 and LS 180 cells and Adriamycin-selected LS 180 sub-lines, P-glycoprotein does not have a major role in Adriamycin resistance. There was correlation between the schedule dependence of Adriamycin cytotoxicity and the role of P-glycoprotein in modulating resistance. In the cell lines in which P-glycoprotein was a major determinant of Adriamycin resistance, the drug exposure (defined as the product of the concentration and the time of treatment) needed to achieve a given percent cell kill was reduced as much as 9-fold when cells were treated for 7 days as compared with 3 hr. By comparison, in cell lines in which P-glycoprotein played a lesser role, the drug exposure necessary to achieve a given percent kill increased under conditions of continuous treatment. In some human colon carcinoma cell lines Pgp appears to play a significant role in resistance to Adriamycin, and this can be overcome by the use of competitive inhibitors of Pgp. The increased sensitivity with continuous treatment observed in cell lines with P-glycoprotein-mediated resistance suggests that administration of drugs by continuous infusion may be valuable in reversing clinical drug resistance mediated predominantly by P-glycoprotein. C1 NCI,MED BRANCH,BLDG 10,RM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 28 TC 119 Z9 131 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1991 VL 49 IS 5 BP 696 EP 703 DI 10.1002/ijc.2910490512 PG 8 WC Oncology SC Oncology GA GP783 UT WOS:A1991GP78300011 PM 1682280 ER PT J AU SEIKI, M SATO, H LIOTTA, LA SCHIFFMANN, E AF SEIKI, M SATO, H LIOTTA, LA SCHIFFMANN, E TI COMPARISON OF AUTOCRINE MECHANISMS PROMOTING MOTILITY IN 2 METASTATIC CELL-LINES - HUMAN-MELANOMA AND RAS-TRANSFECTED NIH3T3 CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-CELLS; MEMBRANE; CHEMOTAXIS; MIGRATION; RESPONSES AB Tumor-cell migration plays an essential role in invasion into surrounding tissues and the formation of metastatic colonies in distant organs. Metastatic human A2058 melanoma and ras-transfected NIH3T3 cells produce autocrine motility factors (AMFs) which stimulate their own motility, and the A2058 cell AMF (AMF/A2058) has been purified. In this study, we partially purified the AMF produced by N-ras-transfected NIH3T3 cells (AMF/NIH3T3) and compared it with AMF/A2058. The two AMFs differed in their gel filtration patterns and heat stability, although both elicited migration of N-ras-transfected NIH3T3 cells. The receptor for AMF/A2058 in A2058 cells is linked to a pertussis-toxin-sensitive GTP-binding protein. Pre-treatment of N-ras-transfected NIH3T3 cells with pertussis toxin also specifically blocked the promotion of motility by AMF/A2058, but did not affect the activity of AMF/NIH3T3. Stimulation of N-ras-transfected NIH3T3 cells by both AMFs elicited an additive response. Thus, the autocrine mechanisms of these two metastatic tumor cell lines are different with regard to the AMF molecules, receptors, and signal transduction pathways. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP SEIKI, M (reprint author), KANAZAWA UNIV,CANC RES INST,DEPT VIROL,13-1 TAKARA MACHI,KANAZAWA,ISHIKAWA 920,JAPAN. RI Seiki, Motoharu/K-9443-2015; SATO, Hiroshi/D-8454-2015 NR 17 TC 13 Z9 13 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1991 VL 49 IS 5 BP 717 EP 720 DI 10.1002/ijc.2910490515 PG 4 WC Oncology SC Oncology GA GP783 UT WOS:A1991GP78300014 PM 1657797 ER PT J AU CLARK, M WEISS, SRB POST, RM AF CLARK, M WEISS, SRB POST, RM TI EXPRESSION OF C-FOS MESSENGER-RNA IN RAT-BRAIN AFTER INTRACEREBROVENTRICULAR ADMINISTRATION OF CORTICOTROPIN-RELEASING HORMONE SO NEUROSCIENCE LETTERS LA English DT Article DE ONCOGENE; C-FOS MESSENGER RNA; CORTICOTROPIN-RELEASING HORMONE; SEIZURE; RAT BRAIN; INSITU HYBRIDIZATION ID LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENES; NERVOUS-SYSTEM; MOUSE-BRAIN; SEIZURES; PROTEIN AB Expression of the proto-oncogene c-fos is known to increase in rat brain following various types of seizures. Measuring c-fos mRNA or protein levels was shown to be a good cellular marker for neurons activated during central nervous system (CNS) excitation. In this study, we used in situ hybridization analysis of c-fos mRNA to determine brain regions activated by a peptide that has been closely linked to stress responsivity and kindling-like seizure activity. Corticotropin-releasing hormone (CRH) was injected into the left lateral ventricle of rats and produced the late onset of seizures between 1.5-5 h after its administration. Rats were sacrificed at various time points after the administration of CRH or sterile water, and c-fos mRNA levels were determined. In the preseizure state, CRH increased c-fos unilaterally in several cerebral cortical structures (most prominently in the dorsal endopiriform nucleus and in the piriform and insular cortices). CRH-induced seizures increased c-fos bilaterally in the same cortical regions, and in addition, in the hippocampus and olfactory bulb. The data are congruous with the hypothesis that intracerebroventricularly (i.c.v.) administered CRH elicits a rapid kindling-like response. RP CLARK, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10 ROOM 3N212,BETHESDA,MD 20892, USA. NR 16 TC 32 Z9 34 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 11 PY 1991 VL 132 IS 2 BP 235 EP 238 DI 10.1016/0304-3940(91)90309-H PG 4 WC Neurosciences SC Neurosciences & Neurology GA GR767 UT WOS:A1991GR76700023 PM 1784425 ER PT J AU COLTON, CA YAO, J TAFFS, RE KERI, JE OSTERGRANITE, ML AF COLTON, CA YAO, J TAFFS, RE KERI, JE OSTERGRANITE, ML TI ABNORMAL PRODUCTION OF INTERLEUKIN-1 BY MICROGLIA FROM TRISOMY-16 MICE SO NEUROSCIENCE LETTERS LA English DT Article DE MICROGLIA; TRISOMY-16 MOUSE; DOWN SYNDROME; INTERLEUKIN-1; INTERFERON ID CENTRAL NERVOUS-SYSTEM; AMEBOID MICROGLIA; INTERFERON-GAMMA; MACROPHAGES; CELLS; EXPRESSION; RECEPTOR; DEFENSE; PROTEIN; DISEASE AB The production of interleukin-1 (IL-1) was examined in cultured CNS microglia obtained from trisomy 16 (Ts16) fetal mouse brain, a model system for studies relevant to Down syndrome (DS). When compared to microglia from their normal littermates, Ts16 microglia produced significantly higher levels of IL-1 activity both before and following stimulation with lipopolysaccharide (LPS). IL-1 release was stimulated by alpha/beta interferon (IFN) in the normal but not Ts16 microglial cultures. The overall level of IL-1 production in normal littermates, however, was still less than that seen in Ts16. Thus, microglia from Ts16 mice may function in an inappropriate manner and, if this abnormally occurs in vivo, may have wide ranging effects on a developing nervous system. C1 NINCDS,BIOPHYS LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BIOCHEM & IMMUNOPHARMACOL UNIT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,DEV GENET LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. RP COLTON, CA (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20057, USA. FU NICHD NIH HHS [HD 19920, HD 19932, HD 24065] NR 41 TC 16 Z9 18 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 11 PY 1991 VL 132 IS 2 BP 270 EP 274 DI 10.1016/0304-3940(91)90318-N PG 5 WC Neurosciences SC Neurosciences & Neurology GA GR767 UT WOS:A1991GR76700032 PM 1723792 ER PT J AU POMMIER, Y CAPRANICO, G ORR, A KOHN, KW AF POMMIER, Y CAPRANICO, G ORR, A KOHN, KW TI LOCAL BASE SEQUENCE PREFERENCES FOR DNA CLEAVAGE BY MAMMALIAN TOPOISOMERASE-II IN THE PRESENCE OF AMSACRINE OR TENIPOSIDE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRAND; SITES; IDENTIFICATION; ADRIAMYCIN; INHIBITION; BINDING AB Several classes of antitumor drugs are known to stabilize topoisomerase complexes in which the enzyme is covalently bound to a terminus of a DNA strand break. The DNA cleavage sites generally are different for each class of drugs. We have determined the DNA sequence locations of a large number of drug-stimulated cleavage sites of topoisomerase II, and find that the results provide a clue to the possible structure of the complexes and the origin of the drug-specific differences. Cleavage enhancements by VM-26 and amsacrine (m-AMSA), which are representative of different classes of topoisomerase II inhibitors, have strong dependence on bases directly at the sites of cleavage. The preferred bases were C at the 3' terminus for VM-26 and A at the 5' terminus for m-AMSA. Also, a region of dyad symmetry of 12 to 16 base pairs Was detected about the enzyme cleavage positions. These results are consistent with those obtained with doxorubicin, although in the case of doxorubicin, cleavage requires the presence of an A at the 3' terminus of at least one the pair of breaks that constitute a double-strand cleavage (Capranico et al., Nucleic Acids Res., 1990, 18:6611). These findings suggest that topoisomerase II inhibitors may stack with one or the other base pair flanking the enzyme cleavage sites. RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Capranico, Giovanni/K-1678-2014 OI Capranico, Giovanni/0000-0002-8708-6454 NR 23 TC 147 Z9 147 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1991 VL 19 IS 21 BP 5973 EP 5980 DI 10.1093/nar/19.21.5973 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GQ238 UT WOS:A1991GQ23800024 PM 1658748 ER PT J AU BIGGAR, RJ AF BIGGAR, RJ TI PREVENTING AIDS NOW SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material RP BIGGAR, RJ (reprint author), NCI,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD 20850, USA. NR 6 TC 11 Z9 11 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 NOV 9 PY 1991 VL 303 IS 6811 BP 1150 EP 1151 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GP488 UT WOS:A1991GP48800004 PM 1747606 ER PT J AU MULVIHILL, JJ HARVEY, EB BOICE, JD CHAKRAVARTI, A MILLER, RW AF MULVIHILL, JJ HARVEY, EB BOICE, JD CHAKRAVARTI, A MILLER, RW TI NORMAL FINDINGS 52 YEARS AFTER INUTERO RADIATION EXPOSURE SO LANCET LA English DT Letter ID ATOMIC-BOMB SURVIVORS; CHILDREN; SYSTEM C1 NCI,BETHESDA,MD 20892. STERLING DRUG INC,MALVERN,PA. RP MULVIHILL, JJ (reprint author), UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15261, USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 9 PY 1991 VL 338 IS 8776 BP 1202 EP 1203 DI 10.1016/0140-6736(91)92063-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GP034 UT WOS:A1991GP03400024 PM 1682607 ER PT J AU TURNER, BH HERKENHAM, M AF TURNER, BH HERKENHAM, M TI THALAMOAMYGDALOID PROJECTIONS IN THE RAT - A TEST OF THE AMYGDALAS ROLE IN SENSORY PROCESSING SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE THALAMUS; LIMBIC; VISCEROSENSORY; EMOTION; SCHIZOPHRENIA; STRESS; INFORMATION PROCESSING ID CORTICAL AFFERENT CONNECTIONS; MEDIAL GENICULATE-BODY; EFFERENT CONNECTIONS; BASAL FOREBRAIN; CENTRAL NUCLEUS; AMYGDALOPETAL PROJECTIONS; TOPOGRAPHIC ORGANIZATION; STRIA TERMINALIS; OLFACTORY-BULB; BRAIN-STEM AB We used the autoradiographic tract-tracing method to define the amygdaloid projection fields after injecting H-3-amino acids into individual thalamic nuclei in the rat. The parvicellular division of the ventroposterior nucleus, the thalamic taste relay, projected lightly to the central and lateral amygdaloid nuclei. The central medial, interanteromedial, and paraventricular thalamic nuclei, viscerosensory relays of the thorax and abdomen, projected heavily to the amygdala. All projected to the basolateral amygdaloid nucleus, the paraventricular nucleus in addition having terminations in the central nucleus, the amygdaloid portion of the nucleus of the stria terminalis, and the amygdalohippocampal transition area. The magnocellular division of the medial geniculate, a thalamic auditory (and, to a moderate degree, a spinothalamic) relay, sent heavy projections to the central, accessory basal, lateral, and anterior cortical nuclei, and to the anterior amygdaloid area and the nucleus of the accessory olfactory tract. Other thalamic nuclei projecting to the amygdala, for which functions could not be associated, were the paratenial and subparafascicular nuclei. The former projected to the lateral, basal, and posterolateral cortical nuclei; the latter projected very lightly to the central, medial, and basal accessory nuclei. These results show that, like the cortical amygdaloid nuclei, which are sensory (olfactory) in nature, the subcortical amygdaloid nuclei must have major sensory functions. These thalamic afferents, when correlated with cortical and brainstem data from the literature, suggested that the amygdala is in receipt of sensory information from many modalities. To uncover the manner by which such information is processed by the amygdala and relayed to effector areas of the brain, six hypothetical mechanisms relating to modality specificity and convergence were posited. By charting sensory-related afferents to all subdivisions of the amygdala, each nucleus was characterized as to its mechanism of information processing. Four proposed amygdaloid systems emerged from this analysis. A unimodal corticomedial amygdaloid system relays pheromonal information from the accessory olfactory bulb to medial basal forebrain and hypothalamic areas. A second system-the lateral-basomedial-collects and combines input from a number of sensory modalities and distributes it to the same basal forebrain and hypothalamic areas as the corticomedial. The central system appears to concentrate the effect of viscerosensory information arriving from multiple brainstem, thalamic, cortical, and amygdaloid sources; this information is combined with significant auditory and spinothalamic inputs from the thalamus and cortex. The central system projects to lateral nuclei in the basal forebrain, hypothalamus, and brainstem. The final system-the basolateral-is a unimodal relay of viscerosensory information from the thalamus to the central nucleus of the amygdala and to the lateral basal forebrain. We argue that all sensory information sorted and restructured by the amygdala to form these systems is distributed directly or indirectly (via a synapse in the basal forebrain or hypothalamus) to diverse brainstem effector mechanisms, an expansion of Nauta's ('58) limbic midbrain concept. The final relays of the first two systems are to motor mechanisms in the medial midbrain and brainstem tegmentum; those of the second two systems project more laterally in the midbrain and brainstem tegmentum. The functional properties of the lateral and medial brainstem areas are quite different. Functional evidence suggests that the four amygdaloid circuits may act in concert as channels by which social communications or other stimuli of behavioral significance initiate sequences of species-typical consummatory behaviors. Together, they appear to form an integrated neural system of emotion, which can operate independent of the corticobulbar/corticospinal system. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. RP TURNER, BH (reprint author), HOWARD UNIV,COLL MED,SCH MED,DEPT ANAT,520 W ST NW,WASHINGTON,DC 20059, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 128 TC 329 Z9 333 U1 0 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 8 PY 1991 VL 313 IS 2 BP 295 EP 325 DI 10.1002/cne.903130208 PG 31 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA GP851 UT WOS:A1991GP85100007 PM 1765584 ER PT J AU RANDAZZO, PA NORTHUP, JK KAHN, RA AF RANDAZZO, PA NORTHUP, JK KAHN, RA TI ACTIVATION OF A SMALL GTP-BINDING PROTEIN BY NUCLEOSIDE DIPHOSPHATE KINASE SO SCIENCE LA English DT Article ID ADENYLATE-CYCLASE; NUCLEOTIDE BINDING; ADP-RIBOSYLATION; ESCHERICHIA-COLI; GS-ALPHA; TUMOR-METASTASIS; CHOLERA-TOXIN; 2 FORMS; EXPRESSION; NM23 AB Genes that encode nucleoside diphosphate kinases (NDKs) have been implicated as regulators of mammalian tumor metastasis and development in Drosophila melanogaster. However, the cellular pathways through which NDKs function am not known. One potential mechanism of regulation is phosphorylation of guanosine diphosphate (GDP) bound to regulatory guanosine triphosphate (GTP) binding proteins. NDK-catalyzed phosphorylation of bound GDP was investigated for the adenosine diphosphate ribosylation factor (ARF), a 21-kilodalton GTP-binding protein that functions in the protein secretion pathway. Bovine liver NDK, recombinant human NDK, and the protein product of the mouse gene nm23-1, which suppresses the metastatic potential of certain tumor cells, used ARF-GDP as a substrate, thereby allowing rapid and efficient production of activated ARF (ARF-GTP) in the absence of nucleotide exchange. These data are consistent with the proposed function of NDK as an activator of a small GTP-binding protein and provide a mechanism of activation for a regulatory GTP-binding protein that is independent of nucleotide exchange. C1 NCI,DIV CENT RES,BIOL CHEM LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06514. NR 35 TC 75 Z9 75 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 8 PY 1991 VL 254 IS 5033 BP 850 EP 853 DI 10.1126/science.1658935 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GN833 UT WOS:A1991GN83300043 PM 1658935 ER PT J AU NUSSINOV, R SMYTHERS, G AF NUSSINOV, R SMYTHERS, G TI TRENDS IN THE 5' VS 3' FLANKS OF OLIGONUCLEOTIDES IN EUKARYOTIC AND PROKARYOTIC GENOMES - THE ASYMMETRIC ROLES PLAYED BY CYTOSINE AND GUANINE SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID DNA-SEQUENCES; TRACTS; CONFORMATION; PROTEIN C1 TEL AVIV UNIV,SACKLER FAC MED,SACLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,ADV SCI COMP LAB,FREDERICK,MD 21702. RP NUSSINOV, R (reprint author), NCI,MATH BIOL LAB,BLDG 10,ROOM 4B-56 LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74102] NR 23 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 7 PY 1991 VL 153 IS 1 BP 111 EP 135 DI 10.1016/S0022-5193(05)80355-8 PG 25 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA GR274 UT WOS:A1991GR27400006 PM 1766250 ER PT J AU MAYER, ML AF MAYER, ML TI MOLECULAR NEUROBIOLOGY - NMDA RECEPTORS CLONED AT LAST SO NATURE LA English DT Editorial Material ID GLUTAMATE RECEPTOR; FUNCTIONAL EXPRESSION; CLONING; COMPLEX; SUBUNIT; FAMILY RP MAYER, ML (reprint author), NICHHD,NEUROPHYSIOL SECT,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013 NR 12 TC 5 Z9 5 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 NOV 7 PY 1991 VL 354 IS 6348 BP 16 EP 17 DI 10.1038/354016a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GN829 UT WOS:A1991GN82900026 PM 1834948 ER PT J AU AACH, RD STEVENS, CE HOLLINGER, FB MOSLEY, JW PETERSON, DA TAYLOR, PE JOHNSON, RG BARBOSA, LH NEMO, GJ AF AACH, RD STEVENS, CE HOLLINGER, FB MOSLEY, JW PETERSON, DA TAYLOR, PE JOHNSON, RG BARBOSA, LH NEMO, GJ TI HEPATITIS-C VIRUS-INFECTION IN POSTTRANSFUSION HEPATITIS - AN ANALYSIS WITH 1ST-GENERATION AND 2ND-GENERATION ASSAYS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NON-B-HEPATITIS; NON-A-HEPATITIS; VIRAL-HEPATITIS; TRANSMITTED VIRUSES; CORE ANTIGEN; ANTIBODY; BLOOD; RECIPIENTS; DONORS AB Background. The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. Methods. We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. Results. Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. Conclusions. Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent). C1 NHLBI,DIV BLOOD DIS & RESOURCES,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NEW YORK BLOOD CTR,NEW YORK,NY 10021. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. BAYLOR COLL MED,HOUSTON,TX 77030. ABBOTT LABS,N CHICAGO,IL 60064. RP AACH, RD (reprint author), MT SINAI MED CTR,1 MT SINAI DR,CLEVELAND,OH 44106, USA. FU NHLBI NIH HHS [N01-HB-42972] NR 22 TC 502 Z9 503 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 7 PY 1991 VL 325 IS 19 BP 1325 EP 1329 DI 10.1056/NEJM199111073251901 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GN470 UT WOS:A1991GN47000001 PM 1656258 ER PT J AU ELDRIDGE, R ALBERSTONE, C AF ELDRIDGE, R ALBERSTONE, C TI GENETIC-BASIS OF FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. RP ELDRIDGE, R (reprint author), NIH,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 NOV 7 PY 1991 VL 325 IS 19 BP 1382 EP 1382 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GN470 UT WOS:A1991GN47000018 ER PT J AU HEALY, B AF HEALY, B TI INVASIVE MANAGEMENT OF PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION INCREASES RISK OF HEMORRHAGE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,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 NOV 6 PY 1991 VL 266 IS 17 BP 2341 EP 2341 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM790 UT WOS:A1991GM79000006 PM 1920737 ER PT J AU HEALY, B AF HEALY, B TI RESULTS OF RADIAL KERATOTOMY EVALUATED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,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 NOV 6 PY 1991 VL 266 IS 17 BP 2341 EP 2341 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM790 UT WOS:A1991GM79000007 PM 1920737 ER PT J AU HEALY, B AF HEALY, B TI TL-201 ABNORMALITIES FOUND INDICATIVE OF ISCHEMIA IN HYPERTROPHIC CARDIOMYOPATHY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,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 NOV 6 PY 1991 VL 266 IS 17 BP 2341 EP 2341 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM790 UT WOS:A1991GM79000008 PM 1920737 ER PT J AU KRUG, MS BERGER, SL AF KRUG, MS BERGER, SL TI REVERSE-TRANSCRIPTASE FROM HUMAN-IMMUNODEFICIENCY-VIRUS - A SINGLE TEMPLATE-PRIMER BINDING-SITE SERVES 2 PHYSICALLY SEPARABLE CATALYTIC FUNCTIONS SO BIOCHEMISTRY LA English DT Article ID AVIAN-MYELOBLASTOSIS VIRUS; RNASE-H ACTIVITY; DEOXYRIBONUCLEIC ACID POLYMERASE; RIBONUCLEOSIDE-VANADYL COMPLEXES; TRANSITION-STATE ANALOGS; DIRECTED DNA-POLYMERASE; LEUKEMIA-VIRUS; ESCHERICHIA-COLI; TUMOR-VIRUSES; DOMAIN-STRUCTURE AB The binding of substrates to recombinant reverse transcriptase from human immunodeficiency virus (HIV) and the natural enzyme from avian myeloblastosis virus (AMV) has been examined by analyzing both the ribonuclease H and the RNA-dependent DNA polymerase activities. With 3'-end-labeled globin mRNA hybridized to (dT)15 as the substrate in the ribonuclease H reaction, the enzymes partially dead-enylated the mRNA in a distributive manner. Under these conditions, there was a rapid initial burst followed by a prolonged, but much slower, steady-state rate. The biphasic reaction made possible determinations of kinetic constants as follows: values for K(m), K(D), and k(cat) were, respectively, 27 nM, 11 nM, and 5 X 10(-3) s-1 for the HIV enzyme and 30 nM, 9 nM, and 5 X 10(-3) s-1, respectively, for the avian enzyme. These constants were used to derive other parameters: The rate of association of the template-primer with reverse transcriptase was approximately 2 X 10(5) M-1 s-1, and the rate of dissociation was approximately 2 X 10(-3) s-1, regardless of the source of the enzyme. The rate of release of the product was essentially equivalent to the value of k.t indicated above for each of the enzymes. The polymerase reaction was evaluated under processive conditions of synthesis; values of K(m) and k(cat) of approximately 6 nM and approximately 2.5 s-1, respectively, for the human enzyme, and approximately 10 nM and approximately 2 s-1, respectively, for the avian enzyme were observed. The interaction of substrates with HIV reverse transcriptase was characterized further with the aid of ribonucleoside-vanadyl complexes. These complexes inhibited the polymerase and ribonuclease H activities of the enzyme competitively with respect to globin mRNA.(dT)15. Values of K(i) ranging from 1 to 3 mM were obtained. With respect to deoxyribonucleoside triphosphate substrates in the polymerase reaction, mixed inhibition was observed. Deoxyribonucleoside triphosphates had no effect on kinetic parameters governing the ribonuclease H activity of the HIV enzyme but apparently facilitated the formation of active enzyme. These data fit a model in which one template-primer binding site serves both the polymerase and the ribonuclease H catalytic sites. C1 NCI,BIOCHEM LAB,GENES & GENE PROD SECT,BLDG 10,ROOM B1B38,BETHESDA,MD 20892. NR 78 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 5 PY 1991 VL 30 IS 44 BP 10614 EP 10623 DI 10.1021/bi00108a003 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN658 UT WOS:A1991GN65800003 PM 1718423 ER PT J AU SOBOL, RW SUHADOLNIK, RJ KUMAR, A LEE, BJ HATFIELD, DL WILSON, SH AF SOBOL, RW SUHADOLNIK, RJ KUMAR, A LEE, BJ HATFIELD, DL WILSON, SH TI LOCALIZATION OF A POLYNUCLEOTIDE BINDING REGION IN THE HIV-1 REVERSE-TRANSCRIPTASE - IMPLICATIONS FOR PRIMER BINDING SO BIOCHEMISTRY LA English DT Article ID MYELOBLASTOSIS VIRUS-RNA; DEPENDENT DNA-POLYMERASE; TRYPTOPHAN TRANSFER-RNA; NUCLEOTIDE-SEQUENCE; AIDS VIRUS; DOMAIN; MECHANISM; PROTEINS; IDENTIFICATION; PROCESSIVITY AB Properties of primer recognition by purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) p66 homodimer have been investigated. Earlier studies had shown that RNA-directed DNA synthesis catalyzed by HIV-1 RT proceeds by an ordered mechanism in which template-primer combines with the free enzyme to form the first complex in the reaction scheme, and it was also shown that primer alone is a competitive inhibitor of template-primer. In this study, enzyme-primer binding has been further characterized utilizing pd(T)8 and pd(T)16 as model primers and UV cross-linking to covalently trap the enzyme-primer complexes. Competition experiments with several authentic primers, including tRNA3Lys, indicate that pd(T)n binds to the kinetically significant primer binding site of RT. Salt reversal experiments suggested that the free energy of pd(T)n binding to RT has a large nonelectrostatic component. Binding of pd(T)n to p66-RT is not affected by dNTPs and does not require the presence of template. The site of UV cross-linking of pd(T)16 was localized to the NH2-terminal half of p66 by use of V8 protease hydrolysis and microsequencing. Our results indicate that a polynucleotide binding site is in close proximity to residues in the peptide comprising amino acids 195 approximately 300. This region could be either a single-stranded template or single-stranded primer binding site; however, we have documented the specificity of binding with oligonucleotides that act as primer in the in vitro DNA synthesis reaction. Therefore, this d(T)16 binding site may be part of a primer-binding groove within the HIV-1 reverse transcriptase. C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DEPT BIOCHEM,BETHESDA,MD 20892. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU NCI NIH HHS [P01-CA29545] NR 41 TC 51 Z9 51 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 5 PY 1991 VL 30 IS 44 BP 10623 EP 10631 DI 10.1021/bi00108a004 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN658 UT WOS:A1991GN65800004 PM 1718424 ER PT J AU QURESHI, SA RIM, M BRUDER, J KOLCH, W RAPP, U SUKHATME, VP FOSTER, DA AF QURESHI, SA RIM, M BRUDER, J KOLCH, W RAPP, U SUKHATME, VP FOSTER, DA TI AN INHIBITORY MUTANT OF C-RAF-1 BLOCKS V-SRC-INDUCED ACTIVATION OF THE EGR-1 PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID NIH 3T3 CELLS; SIGNAL TRANSDUCTION; GENE-EXPRESSION; GROWTH-FACTORS; C-FOS; PROTEIN-KINASES; INDUCIBLE GENE; EARLY RESPONSE; TRANSFORMATION; ONCOGENE AB The protein-tyrosine kinase activity of v-Src leads to the transcriptional activation of the mitogen-responsive transcription factor Egr-1. c-Raf-1 is a serine/threonine protein kinase that has been implicated in the transduction of signals induced by mitogens. The involvement of c-Raf-1 in v-Src-induced Egr-1 expression was investigated using an inhibitory mutant of c-Raf-1. We report here that expression of a kinase-defective mutant of c-Raf-1 inhibits v-Src-induced activation of the Egr-1 promoter. This inhibition is reversed by overexpression of wild type c-Raf-1. Consistent with an involvement of c-Raf-1 in a signaling pathway leading to Egr-1 expression, we find that v-Raf induces Egr-1 promoter activation. These data suggest that c-Raf-1 is a component in an intracellular signaling pathway initiated by v-Src leading to the induction of the mitogen-responsive transcription factor Egr-1. C1 CUNY HUNTER COLL,INST BIOMOLEC STRUCT & FUNCT,695 PK AVE,NEW YORK,NY 10021. CUNY HUNTER COLL,DEPT BIOL SCI,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOLEC GENET,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT CELL BIOL,CHICAGO,IL 60637. OI Kolch, Walter/0000-0001-5777-5016 FU NCI NIH HHS [CA46677]; NCRR NIH HHS [RRO-3037-03] NR 44 TC 67 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 20594 EP 20597 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100005 PM 1939108 ER PT J AU CALDES, T ALEMANY, J ROBCIS, HL DEPABLO, F AF CALDES, T ALEMANY, J ROBCIS, HL DEPABLO, F TI EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I IN DEVELOPING LENS IS COMPARTMENTALIZED SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTALLIN GENE-EXPRESSION; IGF-I; DELTA-1-CRYSTALLIN GENE; EARLY ORGANOGENESIS; EPITHELIAL-CELLS; VITREOUS-HUMOR; MESSENGER-RNA; CHICKEN; RECEPTORS; DIFFERENTIATION AB We, and others, have recently reported that insulin-like growth factor I (IGF-I) mRNA is expressed in multiple tissues during embryogenesis and in whole embryos during early organogenesis. Therefore, it is likely that, in addition to any effect on embryo growth, IGF-I plays a paracrine/autocrine role in development. The embryonic chicken lens, an avascular organ comp posed by a single type of cell that undergoes differentiation in vivo and in vitro, is an ideal model to characterize the paracrine/autocrine action of IGF-I. The lens cells express IGF-I receptors, and respond to exogenous IGF-I with induction of fiber cells differentiation and stimulation of delta-crystallin gene transcription. Whether embryonic lens cells express IGF-I was uncertain. In the present study, we used a sensitive semiquantitative method (reverse transcription of RNA followed by amplification with the polymerase chain reaction) to analyze IGF-I gene expression. An amplified product of the expected length (209 base pairs) was found in days 8, 12, 15, and 19 lenses. At all embryo ages studied, the product was more readily detected in the lens than in the liver, while in eye tissues (excluding lens), IGF-I expression was relatively high. After microdissection of the epithelial cells from the fully differentiated fiber cells, IGF-I expression was detected exclusively in the epithelial cells. IGF-I immunoactivity was found using high performance liquid chromatography followed by radioimmunoassay in the days 8-19 lens extracts, and in primary cultures of isolated epithelial cells. Our previous and present findings show that the lens has all the elements for IGF-I autocrine/paracrine action in development. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 40 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 20786 EP 20790 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100032 PM 1939129 ER PT J AU KARINO, K KADOR, PF BERKOWITZ, B BALABAN, RS AF KARINO, K KADOR, PF BERKOWITZ, B BALABAN, RS TI F-19 NMR QUANTITATION OF LENS ALDOSE REDUCTASE-ACTIVITY USING 3-DEOXY-3-FLUORO-D-GLUCOSE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; DIABETIC COMPLICATIONS; METABOLISM; SPECTROSCOPY; INHIBITORS; EYE AB In the present study we have determined the kinetics of 3-deoxy-3-fluoro-D-glucose (3-FG) as a substrate for the aldose reductase reaction in vitro. In addition, we compared the 3-deoxy-3-fluoro-sorbitol (3-FS) production rates from 3-FG in the intact lens using F-19 NMR with conventional aldose reductase determinations in extracts from the same lenses. The affinity of in vitro aldose reductase for 3-FG was approximately 20 times greater (9.3 mM) than that for glucose (188 mM). An excellent correlation between the rate of 3-FS production in the intact canine lens, determined with F-19 NMR, and extracted aldose reductase activity was observed. The relatively high affinity of aldose reductase for 3-FG and the correlation of 3-FS production with enzyme activity in the intact lens suggests that 3-FS production from 3-FG detected by F-19 NMR could provide an accurate noninvasive determination of aldose reductase activity in the eye lens. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RP KARINO, K (reprint author), NEI,MECHANISM OCULAR DIS LAB,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 26 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 20970 EP 20975 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100061 PM 1939148 ER PT J AU WATANABE, T WADA, N KIM, EE WYCKOFF, HW CHOU, JY AF WATANABE, T WADA, N KIM, EE WYCKOFF, HW CHOU, JY TI MUTATION OF A SINGLE AMINO-ACID CONVERTS GERM-CELL ALKALINE-PHOSPHATASE TO PLACENTAL ALKALINE-PHOSPHATASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHORIOCARCINOMA CELLS; EXPRESSION; GENE; SEMINOMA; SEQUENCE; ISOZYME; CLONING AB Human placental and germ cell alkaline phosphatases (PLAP and GCAP, respectively), are characterized by their differential sensitivities to inhibition by L-leucine, EDTA, and heat. Yet, they differ by only 7 amino acids at positions 15, 67, 68, 84, 241, 254, and 429 within their respective 484 residues. To determine the structural basis and the amino acid(s) involved in these physicochemical differences, we constructed three GCAP mutants by site-directed mutagenesis and six GCAP/PLAP chimeras and then expressed these alkaline phosphatase mutants in COS-1 cells. We report that the differential reactivity of PLAP and GCAP depends critically on a single amino acid at position 429. GCAP with Gly-429 is strongly inhibited by L-leucine, EDTA, and heat, whereas PLAP with Glu-429 is resistant. By substituting Gly-429 of GCAP with a series of amino acids, we demonstrate that the relative sensitivities of these mutants to L-leucine, EDTA, and heat inhibition are, in general, parallel. Mutants in the order of resistance to these treatments are: Glu (most resistant), Asp/Ile/Leu, Gln/Val/Lys, Ser/His, and Arg/Thr/Met/Cys/Phe/Trp/Tyr/Pro/Asn/Ala/Gly (least resistant). However, the Ser-429 and His-429 mutants were more resistant to EDTA and heat inhibition than the wild-type GCAP, but were equally sensitive to L-leucine inhibition. Structural analysis of mammalian alkaline phosphatase modeled on the refined crystal structure of Escherichia coli alkaline phosphatase indicates that the negative charge of Glu-429 of PLAP, which simultaneously stabilizes the protein as a whole and the metal binding specifically, probably acts through interactions with the metal ligand His-320 (His-331 in E. coli alkaline phosphatase). Replacement of codon 429 with Gly in GCAP leads to destabilization and loosening of the metal binding. The data suggest that the natural binding site for L-leucine may be near position 429, with the amino and carboxyl groups of L-leucine interacting with bound phosphate and His-432 (His-412 in E. coli alkaline phosphatase), respectively. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 9S242,BETHESDA,MD 20892. YALE UNIV,DEPT MOLEC BIOPHYS & BIOCHEM,NEW HAVEN,CT 06511. NR 30 TC 23 Z9 24 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 21174 EP 21178 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100091 PM 1939159 ER PT J AU RYBAK, SM SAXENA, SK ACKERMAN, EJ YOULE, RJ AF RYBAK, SM SAXENA, SK ACKERMAN, EJ YOULE, RJ TI CYTOTOXIC POTENTIAL OF RIBONUCLEASE AND RIBONUCLEASE HYBRID PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EOSINOPHIL CATIONIC PROTEIN; RICIN-A-CHAIN; MONOCLONAL-ANTIBODY; EUKARYOTIC RIBOSOMES; SEMINAL RIBONUCLEASE; DIPHTHERIA-TOXIN; ALPHA-SARCIN; SELF-INCOMPATIBILITY; NICOTIANA-ALATA; XENOPUS OOCYTES AB Pancreatic RNase injected into Xenopus oocytes abolishes protein synthesis at concentrations comparable to the toxin ricin yet has no effect on oocyte protein synthesis when added to the extracellular medium. Therefore RNase behaves like a potent toxin when directed into a cell. To explore the cytotoxic potential of RNase toward mammalian cells, bovine pancreatic ribonuclease A was coupled via a disulfide bond to human transferrin or antibodies to the transferrin receptor. The RNase hybrid proteins were cytotoxic to K562 human erythroleukemia cells in vitro with an IC50 around 10(-7)M whereas greater than 10(-5) M native RNase was required to inhibit protein synthesis. Cytotoxicity requires both components of the conjugate since excess transferrin or ribonuclease inhibitors added to the medium protected the cells from the transferrin-RNase toxicity. Compounds that interfere with transferrin receptor cycling and compartmentalization such as ammonium chloride decreased the cytotoxicity of transferrin-RNase. After a dose-dependent lag period inactivation of protein synthesis by transferrin-RNase followed a first-order decay constant. In a clonogenic assay that measures the extent of cell death 1 x 10(-6) M transferrin-RNase killed at least 4 logs or 99.99% of the cells whereas 70 x 10(-6) M RNase was nontoxic. These results show that RNase coupled to a ligand can be cytotoxic. Human ribonucleases coupled to antibodies also may exhibit receptor-mediated toxicities providing a new approach to selective cell killing possibly with less systemic toxicity and importantly less immunogenicity than the currently employed ligand-toxin conjugates. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20896. RP RYBAK, SM (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20896, USA. OI Saxena, Shailendra K/0000-0003-2856-4185 NR 52 TC 108 Z9 111 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 21202 EP 21207 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100096 PM 1939162 ER PT J AU SAXENA, SK RYBAK, SM WINKLER, G MEADE, HM MCGRAY, P YOULE, RJ ACKERMAN, EJ AF SAXENA, SK RYBAK, SM WINKLER, G MEADE, HM MCGRAY, P YOULE, RJ ACKERMAN, EJ TI COMPARISON OF RNASES AND TOXINS UPON INJECTION INTO XENOPUS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EOSINOPHIL CATIONIC PROTEIN; HUMAN CARCINOMA-CELLS; RIBONUCLEASE-ACTIVITY; ESCHERICHIA-COLI; ALPHA-SARCIN; HOMOLOGOUS RECOMBINATION; EUKARYOTIC RIBOSOMES; HUMAN-PLASMA; ANGIOGENIN; SITE AB Several toxins abolish cellular protein synthesis by attacking specific sites in 28 S RNA. One of these toxins, alpha-sarcin, is an RNase that also cleaves nonspecifically on the 3' side of purines in deproteinized RNA. Several other RNases were injected into Xenopus oocytes, examined for their ability to abolish protein synthesis, and compared with alpha-sarcin and ricin. Surprisingly, pancreatic RNase A or B abolished oocyte protein synthesis at concentrations (approximately 0.03 nM) comparable to, or lower than, the amount of alpha-sarcin (approximately 2 nM) or ricin (approximately 0.07 nm) required to abolish protein synthesis. RNases S and T1 only inhibited oocyte protein synthesis when used at concentrations approximately 10 x higher than RNase A whereas RNases C, T2, U2, and nuclease P1 required concentrations approximately 100 times higher than RNase A to abolish protein synthesis. There was a direct correlation between the degradation of oocyte RNA and the inhibition of protein synthesis. The RNase inhibitors RNasin and Inhibit-Ace injected into the oocyte both prevented RNase A from hydrolyzing oocyte rRNA and abolishing protein synthesis. Enzymatically inactive oxidized RNase A did not inhibit protein synthesis when injected into the oocyte. None of the RNases or alpha-sarcin abolished protein synthesis when added to oocyte extracellular medium. Angiogenin is a human plasma protein that induces blood vessel formation in chick embryos, has 35% amino acid identity with RNase A, and cleaves 18 S and 28 S RNA in rabbit reticulocyte lysates (St. Clair, D. K., Rybak, S. M., Riordan, J. F. & Vallee, B. L. (1988) Biochemistry 27, 7263-7268, and references therein). Recombinant angiogenin injected into oocytes abolished protein synthesis, and this toxic effect was inhibited by RNasin but was not inhibited by Inhibit-Ace. Unlike RNase A and the other nucleases that hydrolyzed cellular rRNA, no cleavage of 18 or 28 S RNA by recombinant angiogenin was seen at concentrations 100 x greater than necessary to abolish protein synthesis. Recombinant angiogenin must selectively attack specific RNA(s) or another target in the cell. C1 NIDDKD,GENET & BIOCHEM BRANCH,BLDG 10,RM 9D-15,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892. OI Saxena, Shailendra K/0000-0003-2856-4185 NR 50 TC 80 Z9 83 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 21208 EP 21214 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100097 PM 1939163 ER PT J AU KADOWAKI, T KADOWAKI, H ACCILI, D YAZAKI, Y TAYLOR, SI AF KADOWAKI, T KADOWAKI, H ACCILI, D YAZAKI, Y TAYLOR, SI TI SUBSTITUTION OF ARGININE FOR HISTIDINE AT POSITION 209 IN THE ALPHA-SUBUNIT OF THE HUMAN INSULIN-RECEPTOR - A MUTATION THAT IMPAIRS RECEPTOR DIMERIZATION AND TRANSPORT OF RECEPTORS TO THE CELL-SURFACE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; DENSITY LIPOPROTEIN RECEPTOR; FMS PROTO-ONCOGENE; TYROSINE KINASE; DEPENDENT COVALENT; RESISTANT PATIENT; STRUCTURAL BASIS; PLASMA-MEMBRANE; LIGAND-BINDING; MUTANT ALLELES AB Receptors for insulin and epidermal growth factor contain cysteine-rich domains in the extracellular portion of the molecule. His209 (insulin receptor numbering system) is 1 of 2 amino acid residues that are identically conserved in the cysteine-rich domains of insulin receptors, epidermal growth factor receptors, and other homologous receptors. Previously, we have identified a patient with leprechaunism who is homozygous for a mutation substituting Arg for His209 in the insulin receptor gene (Kadowaki, T., Kadowaki, H., Rechler, M. M., Serrano-Rios, M., Roth, J., Gorden, P., and Taylor, S. 1. (1990) J. Clin. Invest. 86, 254-264). In this investigation, the Arg209 mutant receptor was expressed by transfection of mutant cDNA into NIH-3T3 cells. The mutation impairs several steps in the post-translational processing of the insulin receptor: dimerization of 190-kDa proreceptors into a disulfide linked species, proteolytic cleavage of the proreceptor into alpha- and beta-subunits, and terminal processing of the high mannose form of N-linked oligosaccharide into complex carbohydrate. In addition, the defects in post-translational processing within the endoplasmic reticulum and Golgi apparatus are associated with a marked inhibition in transport of receptors to the plasma membrane. Nevertheless, a small number (almost-equal-to 10%) of the receptors are transported to the cell surface. These receptors on the cell surface bind insulin with normal affinity and have normal tyrosine kinase activity. C1 NIDDKD,DIABET BRANCH,BLDG 10,RM 8S-243,BETHESDA,MD 20892. ASAHI LIFE FDN,INST DIABET CARE & RES,TOKYO 100,JAPAN. UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. NR 43 TC 51 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1991 VL 266 IS 31 BP 21224 EP 21231 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN001 UT WOS:A1991GN00100099 PM 1657953 ER PT J AU OMICHINSKI, JG CLORE, GM SAKAGUCHI, K APPELLA, E GRONENBORN, AM AF OMICHINSKI, JG CLORE, GM SAKAGUCHI, K APPELLA, E GRONENBORN, AM TI STRUCTURAL CHARACTERIZATION OF A 39-RESIDUE SYNTHETIC PEPTIDE CONTAINING THE 2 ZINC-BINDING DOMAINS FROM THE HIV-1 P7-NUCLEOCAPSID PROTEIN BY CD AND NMR-SPECTROSCOPY SO FEBS LETTERS LA English DT Article DE NUCLEOCAPSID PROTEIN-P7; HIV-1; NMR; SOLUTION STRUCTURE ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID-SEQUENCE; NUCLEOCAPSID PROTEIN; 3-DIMENSIONAL STRUCTURES; LEUKEMIA-VIRUS; RNA; TYPE-1; RETROVIRUS; MUTANTS; FINGERS AB A 39-residue peptide (p7-DF) containing the two zinc binding domains of the p7 nucleocapsid protein was prepared by solid-phase peptide synthesis. The solution structure of the peptide was characterized using circular dichroic and nuclear magnetic resonance spectroscopy in both the presence and absence of zinc ions. Circular dichroic spectroscopy indicates that the peptide exhibits a random coil conformation in the absence of zinc but appears to form an ordered structure in the presence of zinc. Two-dimensional nuclear magnetic resonance spectroscopy indicates that the two zinc binding domains within the peptide form stable, but independent, units upon the addition of 2 equivalents of ZnCl2 per equivalent of peptide. Structure calculations on the basis of nuclear Overhauser (NOE) data indicate that the two zinc binding domains have the same polypeptide fold within the errors of the coordinates (approximately 0.5 angstrom for the backbone atoms, the zinc atoms and the coordinating cysteine and histidine ligands). The linker region (Arg17-Gly23) is characterized by a very limited number of sequential NOEs and the absence of any non-sequential NOEs suggest that this region of the polypeptide chain is highly flexible. The latter coupled with the occurrence of a large number of basic residues (four out of seven in the linker region suggests that it may serve to allow adaptable positioning of the nucleic acid recognition sequences within the protein. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 33 TC 79 Z9 82 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 4 PY 1991 VL 292 IS 1-2 BP 25 EP 30 DI 10.1016/0014-5793(91)80825-N PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GQ995 UT WOS:A1991GQ99500007 PM 1959614 ER PT J AU ELWOOD, LJ DOBRZANSKI, D FEUERSTEIN, IM SOLOMON, D AF ELWOOD, LJ DOBRZANSKI, D FEUERSTEIN, IM SOLOMON, D TI PNEUMOCYSTIS-CARINII IN PLEURAL FLUID - THE CYTOLOGIC APPEARANCE SO ACTA CYTOLOGICA LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; AEROSOLIZED PENTAMIDINE; DIAGNOSIS; INFECTION; PNEUMONIA; PATIENT; AIDS; IDENTIFICATION; SPUTUM AB We describe the cytologic appearance of Pneumocystis carinii in pleural fluid of a patient with acquired immunodeficiency syndrome and a rapidly accumulating pleural effusion. The diagnosis of P carinii infection was made by examination of air-dried, Diff-Quik-stained Cytospin preparations of the pleural fluid. The diagnostic appearances of P carinii organisms stained by this method and by the Papanicolaou stain are reviewed. The unusual predominance of the trophozoite forms of the organism in this case made Diff-Quik an ideal special stain for identifying the organisms. Furthermore, this case illustrates a novel presentation of P carinii infection and suggests that P carinii should be considered an etiologic agent in the differential diagnosis of pleural effusion in an immunocompromised host. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT RADIOL,WASHINGTON,DC 20007. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP ELWOOD, LJ (reprint author), NCI,CYTOPATHOL SECT,BLDG 10,ROOM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1991 VL 35 IS 6 BP 761 EP 764 PG 4 WC Pathology SC Pathology GA GT514 UT WOS:A1991GT51400020 PM 1950331 ER PT J AU RAMIREZ, M SANCHEZ, B ARECHAGA, G GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM AF RAMIREZ, M SANCHEZ, B ARECHAGA, G GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM TI DIURNAL-VARIATION AND LEFT-RIGHT DISTRIBUTION OF PYROGLUTAMYL PEPTIDASE-I ACTIVITY IN THE RAT-BRAIN AND RETINA SO ACTA ENDOCRINOLOGICA LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; LH-RH; TRH; HYPOTHALAMUS; DEGRADATION; NUCLEI AB The thyroliberin and luliberin contents exhibit a diurnal rhythm within the brain and an asymmetrical distribution of both neuropeptides has been demonstrated in the hypothalamus. Since they have been described as substrates of pyroglutamyl peptidase I, this activity was analysed in several rat brain regions and other structures, in order to investigate its putative diurnal variations and changes in relation to the distribution of these neuropeptides and/or other susceptible substrates. Fluorometric activity was assayed in the retina, pituitary gland, superior cervical ganglia, pineal gland, some selected brain regions, and serum of adult male rats at six different time points of a 12:12 h light:dark cycle, using pyroglutamyl-beta-naphthylamide as substrate. A significant circadian rhythm was demonstrated in the retina, the hypothalamus, and the intermediate-posterior pituitary lobe. In addition, a small but significant asymmetrical distribution of this activity, at certain time points, was disclosed: The activity was higher in the left than in the right retina at 10 h of the light period, whereas it was predominant in the right side at 01 h of the dark period. Furthermore, the activity was higher in the left anterior than in the right hypothalamic area at 13 and 01 h. These results could be indicative of a role of this enzymatic activity in the control of the functional status of its endogenous substrates. C1 NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP RAMIREZ, M (reprint author), UNIV BASQUE COUNTRY,FAC MED,DEPT PHYSIOL,POB 699,BILBAO,SPAIN. RI Venzon, David/B-3078-2008 NR 12 TC 7 Z9 7 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5598 J9 ACTA ENDOCRINOL-COP JI Acta Endocrinol. PD NOV PY 1991 VL 125 IS 5 BP 570 EP 573 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GW772 UT WOS:A1991GW77200019 PM 1684687 ER PT J AU MCCAUL, TF WILLIAMS, JC THOMPSON, HA AF MCCAUL, TF WILLIAMS, JC THOMPSON, HA TI ELECTRON-MICROSCOPY OF COXIELLA-BURNETII IN TISSUE-CULTURE - INDUCTION OF CELL-TYPES AS PRODUCTS OF DEVELOPMENTAL CYCLE SO ACTA VIROLOGICA LA English DT Article DE COXIELLA-BURNETII; TISSUE CULTURE; DEVELOPMENTAL CYCLE; SPOROGENESIS; ELECTRON MICROSCOPY ID PHASE-I; Q-FEVER AB An in vitro ultrastructural study was carried out on tissue cultures (J774, murine macrophage-like tumour cell line, and BHK-21, baby hamster kidney cell line) persistently infected with C. burnetti to investigate whether the events of cellular differentiation could be visualized. At a given stage of the developmental cycle, a proportion of the cells within the affected phagolysosomes clearly underwent cellular differentiation. The cells initially showed asymmetrical septation, the primary stage of cellular differentiation, and ended with the formation of the differentiated product, a precursor to the small cell. The results verified our initial observation that the events occurring during growth in a phagolysosome represent stages of a complex developmental cycle consisting not only of i) vegetative growth by typical transverse binary fission, but also ii) cellular differentiation. C1 USA,MED INST INFECT DIS,DEPT INTRACELLULAR PATHOGENS,FT DETRICK,FREDERICK,MD 21702. NIAID,OFF DIRECTOR INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. W VIRGINIA UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,MORGANTOWN,WV 26506. RP MCCAUL, TF (reprint author), UNIV QUEENSLAND,CTR ELECTRON MICROSCOPE,ST LUCIA,QLD 4072,AUSTRALIA. NR 21 TC 10 Z9 10 U1 0 U2 1 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57, NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PD NOV PY 1991 VL 35 IS 6 BP 545 EP 556 PG 12 WC Virology SC Virology GA HB173 UT WOS:A1991HB17300008 PM 1687638 ER PT J AU COHEN, SG EVANS, R AF COHEN, SG EVANS, R TI ASTHMA, ALLERGY AND IMMUNOTHERAPY - A HISTORICAL REVIEW .1. SO ALLERGY PROCEEDINGS LA English DT Review RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD NOV-DEC PY 1991 VL 12 IS 6 BP 407 EP 415 DI 10.2500/108854191779114211 PG 9 WC Allergy SC Allergy GA GX377 UT WOS:A1991GX37700010 PM 1794693 ER PT J AU BECHTOLD, WE LUCIER, G BIRNBAUM, LS YIN, SN LI, GL HENDERSON, RF AF BECHTOLD, WE LUCIER, G BIRNBAUM, LS YIN, SN LI, GL HENDERSON, RF TI MUCONIC ACID DETERMINATIONS IN URINE AS A BIOLOGICAL EXPOSURE INDEX FOR WORKERS OCCUPATIONALLY EXPOSED TO BENZENE SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article ID PHYSIOLOGICAL MODEL; B6C3F1 MICE; RATS; METABOLISM AB Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolities with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. the internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL. A linear correlation could be fitted to the time-weighted average (TWA) benzene concentrations, as measured by room air monitoring, and muconic acid in urine (R = 0.9). Workers exposed to benzene concentrations of as little as 4.4 ppm over an 8-hr day possessed higher urinary muconic acid concentrations than did any control individual (p < 0.005). In contrast, no significant difference could be detected for urinary phenol between exposed and control workers at these levels. The ratio between muconic acid and phenol in the urine of the workers exposed to benzene (0.38) was similar to that observed in rats (0.31), but not mice (0.62), exposed to similar amounts of benzene. The assay for muconic acid may potentially be useful as a biological exposure index for benzene at levels approaching the current American Conference of Governmental Industrial Hygienists' threshold limit value (TLV) of 1 ppm; however, improved knowledge of the excretion of muconic acid as a function of both dose and time after exposure will need to be made. C1 CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING,PEOPLES R CHINA. NIEHS,RES TRIANGLE PK,NC 27709. RP BECHTOLD, WE (reprint author), INHALAT TOXICOL RES INST,POB 5890,ALBUQUERQUE,NM 87185, USA. FU NIEHS NIH HHS [222-Y02-ES-20092] NR 17 TC 63 Z9 65 U1 0 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD NOV PY 1991 VL 52 IS 11 BP 473 EP 478 DI 10.1202/0002-8894(1991)052<0473:MADIUA>2.0.CO;2 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA HP692 UT WOS:A1991HP69200006 PM 1746409 ER PT J AU KRAMER, TR SCHOENE, N DOUGLASS, LW JUDD, JT BALLARDBARBASH, R TAYLOR, PR BHAGAVAN, HN NAIR, PP AF KRAMER, TR SCHOENE, N DOUGLASS, LW JUDD, JT BALLARDBARBASH, R TAYLOR, PR BHAGAVAN, HN NAIR, PP TI INCREASED VITAMIN-E INTAKE RESTORES FISH-OIL INDUCED SUPPRESSED BLASTOGENESIS OF MITOGEN-STIMULATED LYMPHOCYTES-T SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE N-3 POLYUNSATURATED FATTY ACIDS; VITAMIN-E; ALPHA-TOCOPHEROL; FISH OIL; CONCANAVALIN-A; LYMPHOCYTES-T; ANTIOXIDANT; LYMPHOCYTE TRANSFORMATION ID FATTY-ACIDS; SUPPLEMENTATION; PLASMA; TOCOPHEROL; IMMUNITY; CELLS; BLOOD AB We sought to determine whether fish-oil supplementation would suppress blastogenesis in vitro of concanavalin A (ConA)-stimulated peripheral blood mononuclear cells (PBMCs) and, if so, whether it could be reversed with increased intake of vitamin E. Healthy males ate a controlled basal diet providing a total of 40% of energy from fat when fed in conjunction with 15 g/d of either placebo oil (PO) or fish-oil concentrate (FOC) fortified with 15 mg-alpha-tocopherol/d for three periods. The subjects were supplemented with PO for 10 wk (PO), with FOC for 10 wk (FOC), and with FOC plus an additional 200 mg alpha-tocopherol/d for 8 wk (FOC + E). During FOC supplementation mitogenic responsiveness of PBMCs to ConA was suppressed, but this effect was reversed by concurrent supplementation with all-rac-alpha-tocopherol (FOC + E). There was a significant positive relationship (P < 0.001) between plasma alpha-tocopherol concentrations and responsiveness of T lymphocytes to ConA. C1 UNIV MARYLAND,DEPT ANIM SCI,COLLEGE PK,MD 20742. NCI,DEPT HLTH & HUMAN SERV,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DIV VITAMINS & CLIN NUTR,NUTLEY,NJ 07110. RP KRAMER, TR (reprint author), USDA,BELTSVILLE HUMAN NUTR RES CTR,VITAMIN & MINERAL & LIPID NUTR LABS,BELTSVILLE,MD 20705, USA. FU NCI NIH HHS [Y01-CN-40620] NR 27 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1991 VL 54 IS 5 BP 896 EP 902 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GN032 UT WOS:A1991GN03200020 PM 1951163 ER PT J AU SWANSON, CA PATTERSON, BH LEVANDER, OA VEILLON, C TAYLOR, PR HELZLSOUER, K MCADAM, PA ZECH, LA AF SWANSON, CA PATTERSON, BH LEVANDER, OA VEILLON, C TAYLOR, PR HELZLSOUER, K MCADAM, PA ZECH, LA TI HUMAN (SE-74)SELENOMETHIONINE METABOLISM - A KINETIC-MODEL SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE SELENIUM; COMPARTMENTAL ANALYSIS; PHARMACOKINETICS; STABLE ISOTOPES; HUMANS ID SELENIUM METABOLISM; SERUM SELENIUM; ISOTOPES; TRACER; MEN; RAT AB A study was undertaken to investigate the pharmacokinetics of an organically bound form of selenium. Six adults received a single oral 200-mu-g dose of Se-74 as L-selenomethionine. A kinetic model was developed to simultaneously account for the appearance and disappearance of the tracer in plasma, urine, and feces. The model included absorption distributed along the gastrointestinal tract, uptake by the liver-pancreas subsystem, enterohepatic recirculation, distribution to two large tissue pools, and transport through four components of the plasma pool. Average turnover time of the plasma components varied from 0.01 to 1.1 d. The turnover time in the liver-pancreas subsystem ranged from 1.6 to 3.1 d. Turnover time ranged from 61 to 86 d in the peripheral tissues with the slowest turnover. The whole-body residence time was approximately five-fold greater than the turnover time of the tissue pool with the slowest turnover, reflecting substantial reutilization of labeled material. C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RP SWANSON, CA (reprint author), NCI,DIV CANC ETIOL,BIOSTAT BRANCH,6130 EXECUT BLVD EPN,ROOM 431,BETHESDA,MD 20892, USA. NR 28 TC 89 Z9 90 U1 0 U2 6 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 NOV PY 1991 VL 54 IS 5 BP 917 EP 926 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GN032 UT WOS:A1991GN03200023 PM 1951166 ER PT J AU SLATTERY, ML JACOBS, DR HILNER, JE CAAN, BJ VANHORN, L BRAGG, C MANOLIO, TA KUSHI, LH LIU, K AF SLATTERY, ML JACOBS, DR HILNER, JE CAAN, BJ VANHORN, L BRAGG, C MANOLIO, TA KUSHI, LH LIU, K TI MEAT CONSUMPTION AND ITS ASSOCIATIONS WITH OTHER DIET AND HEALTH FACTORS IN YOUNG-ADULTS - THE CARDIA STUDY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE BLOOD PRESSURE; BODY SIZE; CHOLESTEROL; DIETARY INTAKE; LIPIDS; MEAT; PHYSICAL ACTIVITY; VEGETARIANS ID BLOOD-PRESSURE; PLASMA-CHOLESTEROL; VEGETARIAN DIET; HEART-DISEASE; LIPOPROTEINS; INGESTION; CANCER; SERUM AB Using cross-sectional data from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed associations between meat consumption and other dietary- and health-status indicators. Less than one percent of this sample (n = 32) ate no red meat or poultry, and another 1% (n = 47) ate red meat or poultry less than once per week. Individuals who ate red meat and poultry less than once per week were less likely to drink alcohol (P = 0.003); reported more physical activity (P less-than-or-equal-to 0.001); had higher Keys scores (P less-than-or-equal-to 0.001); consumed diets higher in carbohydrates, starch, fiber, vitamins A and C, and calcium and lower in energy, fat, and protein (P less-than-or-equal-to 0.001); had smaller body sizes as indicated by the body mass index [calculated as wt(kg)/ht(m2)] (P = 0.01); and had lower concentrations of total serum cholesterol (P = 0.001), low-density-lipoprotein cholesterol (P = 0.001), and triglycerides (P = 0.015) compared with individuals who consumed meat more frequently. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA. NATL HEART LUNG & BLOOD INST,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD. UNIV ALABAMA,DIV GEN & PREVENT MED,BEHAV MED UNIT,BIRMINGHAM,AL 35294. UNIV ALABAMA,CARDIA COORDINATING CTR,BIRMINGHAM,AL 35294. NORTHWESTERN UNIV,SCH MED,DEPT COMMUNITY HLTH & PREVENT MED,CHICAGO,IL 60611. RP SLATTERY, ML (reprint author), UNIV UTAH,SCH MED,50 N MED DR,SALT LAKE CITY,UT 84132, USA. RI Anderson, Jeremy/G-8104-2014; OI Kushi, Lawrence/0000-0001-9136-1175 FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 39 TC 33 Z9 33 U1 0 U2 5 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 NOV PY 1991 VL 54 IS 5 BP 930 EP 935 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GN032 UT WOS:A1991GN03200025 PM 1951168 ER PT J AU BLACKWELDER, WC STORSAETER, J OLIN, P HALLANDER, HO AF BLACKWELDER, WC STORSAETER, J OLIN, P HALLANDER, HO TI ACELLULAR PERTUSSIS VACCINES - EFFICACY AND EVALUATION OF CLINICAL CASE DEFINITIONS SO AMERICAN JOURNAL OF DISEASES OF CHILDREN LA English DT Article ID DIAGNOSIS; COHORT AB The efficacy of two acellular pertussis vaccines was estimated for various clinical case definitions, with and without the requirement of culture confirmation, from a randomized trial in Sweden. Efficacy increased with duration of coughing spasms and when the case definition included whoops or whoops plus at least nine coughing spasms a day. After deletion of clinical cases not believed to be caused by pertussis, efficacies were closer to the higher values for culture-confirmed disease. Nonspecificity of the clinical criterion "21 days of coughing spasms with whoops" resulted in estimates of predictive value for pertussis of 85% for placebo recipients and 56% for vaccinees. We conclude that laboratory confirmation of suspected cases is needed in pertussis vaccine trials. A suggested case definition is 21 days or more of coughing spasms with confirmation by culture, serologic study, or household exposure to culture-confirmed pertussis. C1 NIAID,BETHESDA,MD 20892. KAROLINSKA INST,SACHS CHILDRENS HOSP,DEPT PEDIAT,S-10401 STOCKHOLM 60,SWEDEN. NATL BACTERIOL LAB,S-10521 STOCKHOLM,SWEDEN. NR 17 TC 56 Z9 57 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0002-922X J9 AM J DIS CHILD JI Am. J. Dis. Child. PD NOV PY 1991 VL 145 IS 11 BP 1285 EP 1289 PG 5 WC Pediatrics SC Pediatrics GA GN260 UT WOS:A1991GN26000022 PM 1951222 ER PT J AU HO, GYF NOMURA, AMY NELSON, K LEE, H POLK, BF BLATTNER, WA AF HO, GYF NOMURA, AMY NELSON, K LEE, H POLK, BF BLATTNER, WA TI DECLINING SEROPREVALENCE AND TRANSMISSION OF HTLV-I IN JAPANESE FAMILIES WHO IMMIGRATED TO HAWAII SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE EMIGRATION AND IMMIGRATION; HTLV-I; HTLV-I, TRANSMISSION ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CARRIER MOTHERS; BLOOD-DONORS; NATION-WIDE; LYMPHOMA; RETROVIRUS; ANTIBODIES; INFECTION AB This study examined the seroprevalence and transmission of human T cell lymphotropic virus type I (HTLV-I) in Japanese families who originated in Okinawa, an area in which HTLV-I is endemic, and who were currently residing in Hawaii, a nonendemic area. Among a cohort of Japanese men whose sera were collected in Hawaii in 1967-1975, those of Okinawan ancestry had an HTLV-I seroprevalence of 11.4%. This study, conducted in 1987-1988, sampled 142 index subjects from this male cohort and tested them along with their wives, children, and spouses of the children for HTLV-I antibodies. Seropositivity in their wives was 11.4% and 41.2% among the seronegative and seropositive index subjects, respectively; seropositivity also increased from 29.4% to 35.3% to 58.8% with the husbands' increasing antibody levels by tertiles. Elevated antibody levels may be a marker for infectivity, which is associated with more efficient sexual transmission of HTLV-I. The age-adjusted odds ratio for the association of seropositivity between husband and wife, however, was four times lower than that reported among native Okinawans. In addition, a substantially low seroprevalence (1.3%) was found among their offspring. The decline in HTLV-I transmission in this migrant population may be due to low infectivity in the parent generation who live in a nonendemic environment, increasing numbers of offspring marrying outside of the Okinawan community, and improved living circumstances. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. KUAKINI MED CTR,HONOLULU,HI. ABBOTT LABS,DIV DIAGNOST,N CHICAGO,IL. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA-33644, N01 CP-EB-51023-21] NR 28 TC 23 Z9 23 U1 0 U2 2 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 NOV 1 PY 1991 VL 134 IS 9 BP 981 EP 987 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GQ914 UT WOS:A1991GQ91400008 PM 1951296 ER PT J AU GREM, JL KING, SA CHUN, HG GREVER, MR AF GREM, JL KING, SA CHUN, HG GREVER, MR TI CARDIAC COMPLICATIONS OBSERVED IN ELDERLY PATIENTS FOLLOWING 2'-DEOXYCOFORMYCIN THERAPY SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE 2'-DEOXYCOFORMYCIN; PENTOSTATIN; CARDIAC SIDE EFFECTS ID LYMPHOID MALIGNANCIES; CELL LEUKEMIA; PENTOSTATIN AB Deoxycoformycin (dCF) is an investigational nucleoside with significant activity in hairy cell leukemia, cutaneous T-cell lymphoma, and chronic lymphocytic leukemia. During a 4-year period, 11 patients have experienced cardiac events as a complication of dCF therapy under NCI sponsorship. The cases are presented and recommendations for the administration of dCF to patients with pre-existing heart disease are made. C1 NCI,DIV CANC TREATMENT,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV CHEMOTHERAPEUT PROGRAM,BETHESDA,MD 20892. RP GREM, JL (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 8 TC 20 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 1991 VL 38 IS 3 BP 245 EP 247 DI 10.1002/ajh.2830380320 PG 3 WC Hematology SC Hematology GA GL863 UT WOS:A1991GL86300019 PM 1951329 ER PT J AU MINOR, JR AF MINOR, JR TI FOSCARNET VERSUS GANCICLOVIR IN THE MANAGEMENT OF CYTOMEGALOVIRUS DISEASE IN PATIENTS WITH AIDS SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS DISEASE; INFECTION; RETINITIS; PHOSPHONOFORMATE; INHIBITION; THERAPY RP MINOR, JR (reprint author), NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892, USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD NOV PY 1991 VL 48 IS 11 BP 2478 EP 2479 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GM657 UT WOS:A1991GM65700027 PM 1660675 ER PT J AU MAHAYNI, H MINOR, JR AF MAHAYNI, H MINOR, JR TI MEGESTROL-ACETATE IN AIDS-RELATED CACHEXIA SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID ADVANCED BREAST-CANCER; THERAPY; VIRUS C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP MAHAYNI, H (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,5600 FISHERS LANE,ROCKVILLE,MD 20852, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD NOV PY 1991 VL 48 IS 11 BP 2479 EP 2480 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GM657 UT WOS:A1991GM65700028 PM 1746586 ER PT J AU MAHAYNI, H MINOR, JR AF MAHAYNI, H MINOR, JR TI ANTIRETROVIRAL ACTIVITY OF NALOXONE AND NALTREXONE SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID NATURAL-KILLER CELLS; OPIOID-MEDIATED SUPPRESSION; MORPHINE; INTERFERON C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP MAHAYNI, H (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,5600 FISHERS LANE,ROCKVILLE,MD 20852, USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD NOV PY 1991 VL 48 IS 11 BP 2480 EP 2481 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GM657 UT WOS:A1991GM65700029 PM 1746587 ER PT J AU HAVLIK, RJ AF HAVLIK, RJ TI PREDICTORS OF HYPERTENSION - POPULATION STUDIES SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE BLOOD PRESSURE; HEREDITY; ENVIRONMENT; GENETIC MARKERS; PHENOTYPE AB A genetic influence on the variability of blood pressure in populations has been established. This effect has been demonstrated repeatedly by the presence of familial aggregation of blood pressure; however, a unique bimodal distribution in populations has not been established. About one-third to one-half of the blood pressure variance is explained by heredity with the remainder due to environmental or unknown factors. Direct associations of blood pressure with genetic markers in populations have been described infrequently. However, an association between haptoglobin 1 and increased blood pressure has been reported. This relationship is possibly secondary to increased sodium sensitivity in this genetic subgroup. The familial aggregation of urinary kallikrein as well as sodium-lithium countertransport, and hypertension represents a successful attempt by investigators to identify correlates of intermediate phenotypes of hypertension. The association between restriction fragment length polymorphisms and elevated blood pressure represents an unmet potential. It should be emphasized that any genetic predictive factor will be affected by environmental factors. This interaction provides the opportunity for possible modification or prevention of hypertension by hygienic means. RP HAVLIK, RJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,FED BLDG,ROOM 618,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1991 VL 4 IS 11 BP S586 EP S589 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GW909 UT WOS:A1991GW90900011 PM 1789936 ER PT J AU MOCKRIN, SC HORAN, MJ AF MOCKRIN, SC HORAN, MJ TI SYMPOSIUM - PREDICTORS OF HYPERTENSION - PROCEEDINGS OF A WORKSHOP - INTRODUCTION SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material RP MOCKRIN, SC (reprint author), NHLBI,HYPERTENS & KIDNEY DIS BRANCH,BLDG 4C10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1991 VL 4 IS 11 BP S585 EP S585 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GW909 UT WOS:A1991GW90900010 ER PT J AU GLASSOCK, RJ HIRSCHMAN, GH STRIKER, GE AF GLASSOCK, RJ HIRSCHMAN, GH STRIKER, GE TI WORKSHOP ON THE USE OF RENAL BIOPSY IN RESEARCH ON DIABETIC NEPHROPATHY - A SUMMARY REPORT SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material DE DIABETIC NEPHROPATHY; KIDNEY BIOPSY; RESEARCH STUDIES C1 NIDDKD,FED BLDG,ROOM 102,BETHESDA,MD 20892. NR 0 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1991 VL 18 IS 5 BP 589 EP 592 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA GN264 UT WOS:A1991GN26400009 PM 1951340 ER PT J AU LIU, JM AUERBACH, AD YOUNG, NS AF LIU, JM AUERBACH, AD YOUNG, NS TI FANCONI ANEMIA PRESENTING UNEXPECTEDLY IN AN ADULT KINDRED WITH NO DYSMORPHIC FEATURES SO AMERICAN JOURNAL OF MEDICINE LA English DT Note C1 ROCKEFELLER UNIV,NEW YORK,NY 10021. RP LIU, JM (reprint author), NHLBI,BETHESDA,MD 20892, USA. OI Auerbach, Arleen/0000-0002-6911-8379 NR 5 TC 17 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1991 VL 91 IS 5 BP 555 EP 557 DI 10.1016/0002-9343(91)90197-6 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GR537 UT WOS:A1991GR53700021 PM 1951421 ER PT J AU POLIS, MA MASUR, H AF POLIS, MA MASUR, H TI PROGNOSTIC MARKERS FOR HIV DISEASE PROGRESSION - REPLY SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID CONTROLLED TRIAL; ZIDOVUDINE AZT; INFECTION RP POLIS, MA (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1991 VL 91 IS 5 BP 561 EP 561 DI 10.1016/0002-9343(91)90203-A PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GR537 UT WOS:A1991GR53700027 ER PT J AU ELDREDGE, C MERRITT, S GOYAL, M KULAGA, H KINDT, TJ WIGGINS, R AF ELDREDGE, C MERRITT, S GOYAL, M KULAGA, H KINDT, TJ WIGGINS, R TI ANALYSIS OF T-CELLS AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II MESSENGER-RNA AND PROTEIN-CONTENT AND DISTRIBUTION IN ANTIGLOMERULAR BASEMENT-MEMBRANE DISEASE IN THE RABBIT SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODIES; INTERSTITIAL NEPHRITIS; EXPERIMENTAL GLOMERULONEPHRITIS; CRESCENTIC GLOMERULONEPHRITIS; GOODPASTURES-SYNDROME; RIBONUCLEIC-ACID; RENAL-DISEASE; RAT-KIDNEY; IFN-GAMMA AB The major interacting components of the immune system, major histocompatibility complex (MHC) class I and class II proteins and T cells were analyzed in a model of anti-GBM (glomerular basement membrane) disease in the rabbit that progresses to develop cellular crescents and glomerular and interstitial fibrosis. Class I and II mRNA and protein were measured in isolated glomeruli and whole renal cortex using cDNA probes and monoclonal antibodies. The distribution of T cells and class I and II proteins was assessed by immunofluorescence. Normal glomeruli contained no T cells and were class II negative. By day 4, glomeruli contained MHC class I and II mRNA and protein and class II positive T cells. Although some animals had T cells in the periglomerular area, these cells were class II negative. By day 7 periglomerular T cells were largely class II positive (activated) and there was increased MHC class I and II mRNA and protein in whole renal cortex. Later T cells accumulated in the tubulo-interstitial compartment, which became diffusely positive for MHC classes I and II, but to a variable extent in different animals. Those with high class II mRNA expression also had detectable T cell antigen receptor mRNA by Northern analysis. The authors conclude 1) in this model there was a close association between mRNA abundance and protein expression for both MHC classes I and II in glomeruli and renal cortex as a whole; 2) in this model of glomerular injury there are three phases of activation. The first phase takes place in the glomerulus and is associated with accumulation of activated T cells and MHC class I and II protein in the glomerulus. Phase 2 is associated with the accumulation of periglomerular T cells and their becoming class II positive. There is subsequent dissemination (phase 3) of activated T cells and accumulation of class I and II mRNA and protein throughout the interstitial compartment. This spacial progression of glomerulocentric inflammation is likely associated with degree of injury and permanent loss of renal function. C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIMH,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOGENET LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-39255, DK-38149] NR 65 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1991 VL 139 IS 5 BP 1021 EP 1035 PG 15 WC Pathology SC Pathology GA GN548 UT WOS:A1991GN54800007 PM 1951625 ER PT J AU KRUSZEWSKI, FH HENNINGS, H YUSPA, SH TUCKER, RW AF KRUSZEWSKI, FH HENNINGS, H YUSPA, SH TUCKER, RW TI REGULATION OF INTRACELLULAR FREE CALCIUM IN NORMAL MURINE KERATINOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GROWTH REGULATION; DIFFERENTIATION; CALCIUM TRANSPORT; SERUM ID MOUSE EPIDERMAL-CELLS; PROTEIN KINASE-C; TERMINAL DIFFERENTIATION; GROWTH-FACTOR; EXPRESSION; CA-2+; PROLIFERATION; METABOLISM; RECEPTOR; ION AB Cultured normal murine keratinocytes maintain a basal cell phenotype in medium with a Ca2+ concentration of 0.05 mM and differentiate when exposed for 28-48 h to medium supplemented with extracellular Ca2+ >0.10 mM. Previous studies have documented Ca2+ activation of signaling pathways in the plasma membrane and tightly regulated cellular responses to small incremental changes in extracellular Ca2+. To determine if changes in free cytosolic calcium (Ca(i)) are associated with these early signaling events, digital image analysis of fura-2-loaded keratinocytes was used to measure Ca(i) in individual cells. Basal keratinocytes in 0.05 mM Ca2+ display a biphasic Ca(i) increase when exposed to >0.1 mM Ca2+ in serum-containing medium. These separate phases were controlled by different media components. Initial peak Ca(i) occurred rapidly (within 60 s), was transient (lasting <5 min), and resulted from release of 10-20% of total intracellular Ca2+ stores. Peak Ca(i) depended on serum concentration and was independent of extracellular Ca2+. This transient Ca(i) response was lost as keratinocytes differentiated. Plateau Ca(i) level was sustained (>24 h) and depended on extracellular Ca2+, but not serum. The magnitude of plateau Ca(i) increased incrementally following increases in extracellular Ca2+ as small as 0.02 mM. A similar biphasic Ca(i) increase was noted in cultures of murine dermal fibroblasts stimulated by 1.2 mM Ca2+ and serum. However, fibroblasts did not lose the serum response in high-Ca2+ medium, and plateau Ca(i) was not sensitive to small changes in extracellular Ca2+. The sensitivity of keratinocytes to stimulation of a prolonged Ca(i) plateau by small increases of extracellular Ca2+ may contribute to the induction of differentiation-specific genes and to terminal differentiation in this cell type. C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,SB 21D,BALTIMORE,MD 21205. NCI,BETHESDA,MD 20892. NR 48 TC 45 Z9 45 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1991 VL 261 IS 5 BP C767 EP C773 PN 1 PG 7 WC Physiology SC Physiology GA GQ780 UT WOS:A1991GQ78000005 PM 1951667 ER PT J AU CASTILLO, CE KATZ, A SPENCER, MK ZHEN, Y NYOMBA, BL AF CASTILLO, CE KATZ, A SPENCER, MK ZHEN, Y NYOMBA, BL TI FASTING INHIBITS INSULIN-MEDIATED GLYCOLYSIS AND ANAPLEROSIS IN HUMAN SKELETAL-MUSCLE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE LACTATE; MALATE; CITRATE; GLYCOGEN SYNTHASE; CARBOHYDRATE OXIDATION ID GLUCOSE-METABOLISM; GLYCOGEN-SYNTHASE; FATTY-ACIDS; RAT-HEART; STARVATION; EXERCISE; PHOSPHORYLATION; PHOSPHATASE; BINDING; CYCLE AB Euglycemic (approximately 5.5 mM) hyperinsulinemic (60 mU.m-2.min-1) clamps were performed for 2 h after a 10-h fast and after a prolonged (72-h) fast. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. The rate of whole body glucose disposal was approximately 50% lower during the clamp after the 72-h fast (P less-than-or-equal-to 0.001). The increase in carbohydrate (CHO) oxidation (which is proportional to glycolysis) during the clamp after the 10-h fast (to 13.8 +/- 1.5-mu-mol.kg fat free mass-1.min-1) was completely abolished during the clamp after the 72-h fast (1.7 +/- 0.6; P less-than-or-equal-to 0.001). During the clamp after the 10-h fast, postphosphofructokinase (PFK) intermediates and malate in muscle increased, whereas glutamate decreased (P less-than-or-equal-to 0.05-0.001 vs. basal) and citrate did not change. During the clamp after the 72-h fast, there were no significant changes in post-PFK intermediates or glutamate (P > 0.05 vs. basal), but there was a decrease in citrate (P less-than-or-equal-to 0.01 vs. basal). Euglycemic hyperinsulinemia increased glycogen synthase fractional activity in muscle under both conditions but to a greater extent after the 72-h fast (P less-than-or-equal-to 0.01). It is concluded that insulin (after 10-h fast) increases glycolytic flux and the content of malate in muscle, which is probably due to increased anaplerosis. The decrease in citrate during hyperinsulinemia after the 72-h fast indicates that insulin activated the tricarboxylic acid (TCA) cycle but that the replenishment of TCA cycle intermediates normally observed (10-h fast) was blocked, possibly due to inadequate provision of three-carbon intermediates for anaplerosis. These data demonstrate that prolonged fasting can increase and decrease insulin-mediated activation of processes associated with CHO metabolism in human skeletal muscle. C1 NIDDKD,CLIN DIABETES & NUTR SECT,PHOENIX,AZ 85106. UNIV ILLINOIS,DEPT KINESIOL,URBANA,IL 61801. NR 37 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1991 VL 261 IS 5 BP E598 EP E605 PN 1 PG 8 WC Physiology SC Physiology GA GQ780 UT WOS:A1991GQ78000034 PM 1951684 ER PT J AU VENTURA, C CAPOGROSSI, MC SPURGEON, HA LAKATTA, EG AF VENTURA, C CAPOGROSSI, MC SPURGEON, HA LAKATTA, EG TI K-OPIOID PEPTIDE RECEPTOR STIMULATION INCREASES CYTOSOLIC PH AND MYOFILAMENT RESPONSIVENESS TO CA2+ IN CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE INDO-1; SNARF-1 ID PROTEIN-KINASE; PHORBOL ESTER; CELLS; SYSTEMS; AGONIST; RELEASE; CA-2+ AB Although kappa- and delta-opioid receptors on mammalian cardiac myocytes have been discovered recently, the intracellular effects that result from stimulation of these receptors remain unknown. We examine the effects of a rapid and brief exposure to a kappa-opioid receptor agonist on intracellular Ca2+, pH, and cell length in individual isolated rat ventricular cells. The specific kappa-agonist trans-dl-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide (U-50488H) (methane sulfonate salt) caused a transient increase in cytosolic pH (pH(i)) measured from the change in SNARF-1 fluorescence and an increase in cytosolic [Ca2+] (Ca(i)), indexed by a change in indo-1 fluoresence. The initial Ca(i) increase often was followed by Ca(i) oscillations. Both pH(i) and Ca(i) effects were blocked by the specific antagonist kappa-opioid receptor l-(N-furylmethyl)-alpha-normetazocine methane-sulfonate (Mr 1452). The amplitude of contraction that accompanied the Ca(i) increase elicited by U-50488H was greater than that associated with a similar increase in Ca(i) elicited by electrical stimulation or by the rapid exposure of cells to caffeine. Thus an acute and brief kappa-opioid receptor stimulation of cardiac cells leads to an increase in Ca(i) and pH(i). The pH(i) increase was abolished by 1) blockade of the Na+-H+ exchanger by ethyl isopropyl amiloride and 2) inhibition of protein kinase C (PKC) activity via pretreatment with staurosporine or prolonged incubation with 4-beta-phorbol 12-myristate 13-acetate. These maneuvers did not abolish the U-50488H-induced increase in Ca(i). Thus the kappa-opioid-induced increase in pH(i) and associated enhanced myofilament response to Ca2+ in individual heart cells likely is mediated, at least in part, via PKC activation of Na+-H+ exchange. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. UNIV BOLOGNA,DEPT BIOCHEM,I-40127 BOLOGNA,ITALY. NR 20 TC 62 Z9 64 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD NOV PY 1991 VL 261 IS 5 BP H1671 EP H1674 PN 2 PG 4 WC Physiology SC Physiology GA GQ781 UT WOS:A1991GQ78100045 ER PT J AU SIMONSICK, EM AF SIMONSICK, EM TI PERSONAL HEALTH HABITS AND MENTAL-HEALTH IN A NATIONAL PROBABILITY SAMPLE SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB This investigation examined the relationship between six of seven Alameda County health habits and four dietary practices and three indices of mental health in a probability sample of 2,436 adults 20 to 64 years of age, residing in the coterminous United States. The sample consisted of all respondents to Wave 2 of the National Survey of Personal Health Practices and Consequences conducted in 1980. I found a strong relationship between poor health habits and risk of depressed mood and "nervous breakdown." The magnitude and direction of the association varied by sex, age group, the specific habit examined, and the measure of mental health used. For women, infrequent participation in active sports consistently predicted mental health problems, but was not important for men. In young men, I found no association between health habits and mental health. Dietary practices and mental health generally showed a negative association, especially among men, for whom those reporting good practices had a significantly higher risk of nervous breakdown than those reporting poor practices. RP SIMONSICK, EM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [AG 00161] NR 0 TC 24 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV-DEC PY 1991 VL 7 IS 6 BP 425 EP 437 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA HH030 UT WOS:A1991HH03000015 PM 1790054 ER PT J AU SALIVE, ME PARKINSON, MD AF SALIVE, ME PARKINSON, MD TI PREVENTIVE MEDICINE RESIDENTS - A NATIONAL SURVEY SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Little is known about those physicians who pursue graduate medical education in preventive medicine, including aerospace medicine, general preventive medicine and public health, and occupational medicine. We surveyed resident physicians about their academic background, financial environment, clinical activities, and professional goals. A total of 147 residents (30%) responded from a population of 498 residents. The data suggest a lack of available information about preventive medicine training and careers among medical students who subsequently pursue such training. Their economic environment is extremely diverse, with a wide range of salary, "moonlighting" hours, educational loans, and service obligations. Although the median annual salary ($24,700) is similar to the national average resident salary, 32% of respondents earned less than $20,000, and 95% have educational debts averaging $30,900. Sixty-two percent of respondents perform clinical work in their residency, whereas 76% desire future clinical work as part of their practice. This gap is most pronounced in general preventive medicine and public health. The residents express a wide range of interests in future practice of preventive medicine; 54% are interested in government work, and 33% desire academic careers. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV-DEC PY 1991 VL 7 IS 6 BP 445 EP 449 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA HH030 UT WOS:A1991HH03000017 PM 1790056 ER PT J AU COWDRY, RW GARDNER, DL OLEARY, KM LEIBENLUFT, E RUBINOW, DR AF COWDRY, RW GARDNER, DL OLEARY, KM LEIBENLUFT, E RUBINOW, DR TI MOOD VARIABILITY - A STUDY OF 4 GROUPS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; DIURNAL-VARIATIONS; DEPRESSION; RELIABILITY; SCALE; PHARMACOTHERAPY; DYSPHORIA; SYMPTOMS; VALIDITY AB Objective: The authors' goal was to determine whether self-rated patterns of mood regulation differed among patients with major depression, patients with borderline personality disorder, patients with premenstrual syndrome (PMS), and normal subjects. Method: Fourteen days of morning and evening mood self-ratings on a visual analog scale were analyzed for 65 female subjects (10 with major depression, 16 with borderline personality disorder, 15 with PMS, and 24 without psychiatric diagnoses). For each individual, the mean and standard deviation of morning and evening ratings, the mean absolute change in mood from one day to the next, and the change from morning to evening were determined. Results: The four groups differed significantly on every measure of mood and mood variability except diurnal variation. As expected, the group with major depression had the lowest global ratings and a low degree of variability. The group with borderline personality disorder was less depressed than the group with major depression and showed a high degree of mood variability. Auto-correlation analysis suggested that mood ratings in borderline personality disorder vary randomly from one day to the next. The mood variability over the 14 days of the patients with PMS was significantly greater than that of normal subjects. Conclusions: The visual analog scale can capture patterns of mood and mood variability thought to be typical of these diagnostic groups. Mood disorders differ not only in the degree of abnormal mood but also in the pattern of mood variability, suggesting that mechanisms regulating mood stability may differ from those regulating overall mood state. C1 NIMH,CLIN & RES SERV BRANCH,BETHESDA,MD 20892. NIMH,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NR 32 TC 96 Z9 97 U1 0 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 NOV PY 1991 VL 148 IS 11 BP 1505 EP 1511 PG 7 WC Psychiatry SC Psychiatry GA GM202 UT WOS:A1991GM20200007 PM 1928464 ER PT J AU CLAYTON, PJ GROVE, WM CORYELL, W KELLER, M HIRSCHFELD, R FAWCETT, J AF CLAYTON, PJ GROVE, WM CORYELL, W KELLER, M HIRSCHFELD, R FAWCETT, J TI FOLLOW-UP AND FAMILY STUDY OF ANXIOUS DEPRESSION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PANIC DISORDER; MAJOR DEPRESSION; ATTACKS; CLASSIFICATION; PREDICTORS; SUICIDE AB Objective: The failure of the concept of anxious depression to find its way into DSM-III-R led the authors to conclude that a further report on the occurrence of anxiety symptoms in depressed subjects is indicated. Method: The subjects were 327 consecutively evaluated inpatients and outpatients with primary unipolar depressive disorder at five university medical centers participating in the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression - Clinical studies. The authors restricted their sample selection to patients with primary depressive disorder so that patients with other preexisting psychiatric disorders, especially anxiety disorders, would not contaminate the symptom picture, family studies, or follow-up. They examined six anxiety symptoms and derived a new anxiety summary score to show the effect of anxiety in depression on family data and 5-year outcome. Results: Depressed subjects with higher ratings for anxiety took longer to recover. There was also a significant relationship between anxiety in depressed probands and the risk for primary unipolar depressive disorder, but not anxiety disorders or alcoholism, among 832 blindly interviewed first-degree relatives. Conclusions: These data confirm the usefulness of subdividing depressed patients according to anxiety symptoms: psychic and somatic symptoms of anxiety, taken together, significantly predict family illness and course. The data also emphasize the wisdom of requiring that generalized anxiety disorder not be diagnosed in the presence of a mood disorder. Clearly, symptoms of anxiety coexist with depression and need to be recognized for the effective treatment of the underlying depressive disorder. C1 NIMH,NIMH COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIES,BETHESDA,MD 20892. RP CLAYTON, PJ (reprint author), UNIV MINNESOTA,DEPT PSYCHIAT,BOX 77 UMHC,MINNEAPOLIS,MN 55455, USA. FU NIMH NIH HHS [R01 MH025478, MH-25430] NR 30 TC 195 Z9 203 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1991 VL 148 IS 11 BP 1512 EP 1517 PG 6 WC Psychiatry SC Psychiatry GA GM202 UT WOS:A1991GM20200008 PM 1928465 ER PT J AU PIGOTT, TA ALTEMUS, M RUBENSTEIN, CS HILL, JL BIHARI, K LHEUREUX, F BERNSTEIN, S MURPHY, DL AF PIGOTT, TA ALTEMUS, M RUBENSTEIN, CS HILL, JL BIHARI, K LHEUREUX, F BERNSTEIN, S MURPHY, DL TI SYMPTOMS OF EATING DISORDERS IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NERVOSA AB Objective: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders. Method: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory. Results: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects. Conclusions: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders. RP PIGOTT, TA (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 49 Z9 51 U1 0 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1991 VL 148 IS 11 BP 1552 EP 1557 PG 6 WC Psychiatry SC Psychiatry GA GM202 UT WOS:A1991GM20200015 PM 1928472 ER PT J AU LITMAN, RE HOMMER, DW CLEM, T ORNSTEEN, ML OLLO, C PICKAR, D AF LITMAN, RE HOMMER, DW CLEM, T ORNSTEEN, ML OLLO, C PICKAR, D TI CORRELATION OF WISCONSIN CARD SORTING TEST-PERFORMANCE WITH EYE TRACKING IN SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PURSUIT; MOVEMENTS AB The authors studied the relationship between performance on the Wisconsin Card Sorting Test and on the Trailmaking-B test and measures of smooth pursuit eye movements in 12 patients with chronic schizophrenia and 12 normal volunteers. They found that performance on the Wisconsin Card Sorting Test was significantly correlated with measures of smooth pursuit eye movements in schizophrenic patients but not in normal subjects. Trailmaking-B scores, however, were unrelated to smooth pursuit eye movements in either group. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. VET ADM MED CTR,SEATTLE,WA 98108. RP LITMAN, RE (reprint author), NIMH,CLIN STUDIES SECT,CLIN NEUROSCI BRANCH,NIH BLDG 10-4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 37 Z9 37 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1991 VL 148 IS 11 BP 1580 EP 1582 PG 3 WC Psychiatry SC Psychiatry GA GM202 UT WOS:A1991GM20200021 PM 1928477 ER PT J AU ADINOFF, B NEMEROFF, CB BISSETTE, G MARTIN, PR LINNOILA, M AF ADINOFF, B NEMEROFF, CB BISSETTE, G MARTIN, PR LINNOILA, M TI INVERSE RELATIONSHIP BETWEEN CSF TRH CONCENTRATIONS AND THE TSH RESPONSE TO TRH IN ABSTINENT ALCOHOL-DEPENDENT PATIENTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; DEPRESSION AB The authors performed the thyrotropin-releasing hormone (TRH) stimulation test and measured CSF concentrations of TRH in 13 abstinent alcohol-dependent subjects. They found an inverse correlation between the thyrotropin (TSH) response to TRH and endogenous CSF TRH concentrations. This finding supports the hypothesis that as the concentration of CSF TRH increases, anterior pituitary TRH receptor density decreases, resulting in a blunted TSH response to TRH stimulation. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROCKVILLE,MD 20852. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Martin, Peter/A-7738-2008 NR 7 TC 21 Z9 21 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1991 VL 148 IS 11 BP 1586 EP 1588 PG 3 WC Psychiatry SC Psychiatry GA GM202 UT WOS:A1991GM20200023 PM 1656797 ER PT J AU JONES, JM LEVINE, IS ROSENBERG, AA AF JONES, JM LEVINE, IS ROSENBERG, AA TI HOMELESSNESS RESEARCH, SERVICES, AND SOCIAL-POLICY - INTRODUCTION TO THE SPECIAL ISSUE SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material C1 NIMH,ROCKVILLE,MD 20857. RP JONES, JM (reprint author), AMER PSYCHOL ASSOC,1200 17TH ST NW,WASHINGTON,DC 20036, USA. NR 5 TC 13 Z9 13 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1991 VL 46 IS 11 BP 1109 EP 1111 DI 10.1037//0003-066X.46.11.1109 PG 3 WC Psychology, Multidisciplinary SC Psychology GA GP067 UT WOS:A1991GP06700002 ER PT J AU LEVINE, IS HUEBNER, RB AF LEVINE, IS HUEBNER, RB TI HOMELESS PERSONS WITH ALCOHOL, DRUG, AND MENTAL-DISORDERS - INTRODUCTION TO SECTION ONE SO AMERICAN PSYCHOLOGIST LA English DT Article C1 NIAAA,ROCKVILLE,MD 20852. RP LEVINE, IS (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1991 VL 46 IS 11 BP 1113 EP 1114 PG 2 WC Psychology, Multidisciplinary SC Psychology GA GP067 UT WOS:A1991GP06700003 ER PT J AU DENNIS, DL BUCKNER, JC LIPTON, FR LEVINE, IS AF DENNIS, DL BUCKNER, JC LIPTON, FR LEVINE, IS TI A DECADE OF RESEARCH AND SERVICES FOR HOMELESS MENTALLY-ILL PERSONS - WHERE DO WE STAND SO AMERICAN PSYCHOLOGIST LA English DT Article ID FOUNDATION PROGRAM; LOS-ANGELES; HEALTH; ILLNESS; CITY; MEN C1 HUMAN RESOURCES ADM,NEW YORK,NY. NIMH,ROCKVILLE,MD 20857. RP DENNIS, DL (reprint author), POLICY RES ASSOCIATES INC,262 DELAWARE AVE,DELMAR,NY 12054, USA. NR 78 TC 80 Z9 80 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1991 VL 46 IS 11 BP 1129 EP 1138 DI 10.1037/0003-066X.46.11.1129 PG 10 WC Psychology, Multidisciplinary SC Psychology GA GP067 UT WOS:A1991GP06700005 PM 1772150 ER PT J AU MCCARTY, D ARGERIOU, M HUEBNER, RB LUBRAN, B AF MCCARTY, D ARGERIOU, M HUEBNER, RB LUBRAN, B TI ALCOHOLISM, DRUG-ABUSE, AND THE HOMELESS SO AMERICAN PSYCHOLOGIST LA English DT Article ID POLICY C1 STABILIZAT SERV,BOSTON,MA. NIAAA,ROCKVILLE,MD 20852. RP MCCARTY, D (reprint author), MASSACHUSETTS DEPT PUBL HLTH,150 TREMONT ST,BOSTON,MA 02111, USA. FU NIAAA NIH HHS [R18-AA007915] NR 85 TC 61 Z9 61 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1991 VL 46 IS 11 BP 1139 EP 1148 DI 10.1037//0003-066X.46.11.1139 PG 10 WC Psychology, Multidisciplinary SC Psychology GA GP067 UT WOS:A1991GP06700006 PM 1772151 ER PT J AU DRAKE, RE OSHER, FC WALLACH, MA AF DRAKE, RE OSHER, FC WALLACH, MA TI HOMELESSNESS AND DUAL DIAGNOSIS SO AMERICAN PSYCHOLOGIST LA English DT Article ID MENTALLY-ILL PERSONS; SUBSTANCE ABUSE; PSYCHIATRIC-DISORDERS; CO-OCCURRENCE; GROUP-THERAPY; ALCOHOL-USE; COMMUNITY; SCHIZOPHRENIA; SUPPORTS; SHELTER C1 NIMH,ROCKVILLE,MD 20857. DUKE UNIV,DURHAM,NC 27706. RP DRAKE, RE (reprint author), NEW HAMPSHIRE DARTMOUTH PSYCHIAT RES CTR,2 WHIPPLE PL,LEBANON,NH 03766, USA. FU NIAAA NIH HHS [1-R01-AA-08341-01]; NIMH NIH HHS [1-K02-MH-00839-01, 1-R18-MH-46072-01] NR 87 TC 176 Z9 179 U1 4 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1991 VL 46 IS 11 BP 1149 EP 1158 DI 10.1037/0003-066X.46.11.1149 PG 10 WC Psychology, Multidisciplinary SC Psychology GA GP067 UT WOS:A1991GP06700007 PM 1772152 ER PT J AU BOROK, Z GILLISSEN, A BUHL, R HOYT, RF HUBBARD, RC OZAKI, T RENNARD, SI CRYSTAL, RG AF BOROK, Z GILLISSEN, A BUHL, R HOYT, RF HUBBARD, RC OZAKI, T RENNARD, SI CRYSTAL, RG TI AUGMENTATION OF FUNCTIONAL PROSTAGLANDIN-E LEVELS ON THE RESPIRATORY EPITHELIAL SURFACE BY AEROSOL ADMINISTRATION OF PROSTAGLANDIN-E SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID IDIOPATHIC PULMONARY FIBROSIS; INTERSTITIAL LUNG-DISEASES; HUMAN ALVEOLAR MACROPHAGE; FIBROBLAST GROWTH; CHRONIC INFLAMMATION; DISTRESS SYNDROME; UNKNOWN CAUSE; TRACT; DISORDERS; MODULATION AB Prostaglandin E (PGE), a cyclooxygenase metabolite normally present in high concentrations in respiratory epithelial lining fluid (ELF), is capable of suppressing mesenchymal cell proliferation mediated by polypeptide-derived growth factors. Although PGE is normally abundant in respiratory ELF, PGE levels in ELF of individuals with idiopathic pulmonary fibrosis (IPF), a fibrotic lung disorder characterized by intraalveolar mesenchymal cell accumulation and fibrosis, were found to be 50% lower than normal (p < 0.01): that is, a relative PGE "deficiency" in ELF may enhance intraalveolar mesenchymal cell proliferation in IPF. With this background, It is rational to consider augmenting PGE levels in ELF as a future therapy for IPF. Since systemic administration of PGE is associated with significant adverse effects, in vitro and experimental animal studies were carried out to evaluate whether aerosol PGE administration could augment ELF PGE levels. Greater than 50% of a solution of PGE1 could be placed in droplets < 3 gm mass median aerodynamic diameter without loss of function. Aerosolization of PGE1 to sheep (n = 14) resulted in a marked augmentation of ELF PGE1 levels (preaerosol 20 +/- 7 nM, 30 min postaerosol 1,150 +/- 210 nM; p < 0.0 to 0.1). ELF PGE1 levels remained elevated for up to 2 h (p < 0.05 compared with baseline) and returned to baseline by 3 h (p > 0.2). Lung interstitial fluid (lymph) PGE, levels increased slightly, but to levels far less than ELF levels (preaerosol 7 +/- 1 nM, 30 min postaerosol 13 +/- 2 nM; p < 0.01), and plasma PGE1 levels did not change (p > 0.1). No systemic adverse effects were observed. The PGE1 deposited on the alveolar epithelial surface was functional as evidenced by the ability of ELF recovered 30 min postaerosol to suppress lung fibroblast proliferation compared with pretherapy ELF (p < 0.001). Thus, it is possible to significantly augment the levels of functional PGE1 in lung ELF by aerosolization, suggesting a potential form of therapy to suppress intraalveolar mesenchymal cell accumulation in respiratory ELF PGE deficiency disorders, such as IPF. C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG SECT,BETHESDA,MD 20892. NR 39 TC 88 Z9 88 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD NOV PY 1991 VL 144 IS 5 BP 1080 EP 1084 PG 5 WC Respiratory System SC Respiratory System GA GP082 UT WOS:A1991GP08200014 PM 1952435 ER PT J AU CHIKUMA, T HANAOKA, K LOH, YP KATO, T ISHII, Y AF CHIKUMA, T HANAOKA, K LOH, YP KATO, T ISHII, Y TI A COLORIMETRIC ASSAY FOR MEASURING PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID RAT ANTERIOR-PITUITARY; PORCINE PITUITARY; XENOPUS-LAEVIS; ASCORBIC-ACID; ENZYME; GLYCINE; PURIFICATION; COPPER; SKIN; MECHANISM C1 YOKOHAMA CITY UNIV,GRAD SCH INTEGRATED SCI,MOLEC RECOGNIT LAB,YOKOHAMA 236,JAPAN. NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. RP CHIKUMA, T (reprint author), SHOWA COLL PHARMACEUT SCI,DEPT PHARMACEUT ANALYT CHEM,TOKYO 154,JAPAN. NR 29 TC 12 Z9 12 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1991 VL 198 IS 2 BP 263 EP 267 DI 10.1016/0003-2697(91)90423-Q PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GL766 UT WOS:A1991GL76600008 PM 1799210 ER PT J AU MARKELLO, TC GUO, JR GAHL, WA AF MARKELLO, TC GUO, JR GAHL, WA TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY OF LIPIDS FOR THE IDENTIFICATION OF HUMAN METABOLIC DISEASE SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID LIGHT-SCATTERING; PHOSPHOLIPIDS; SEPARATION; DETECTOR; ACIDS RP MARKELLO, TC (reprint author), NICHHD, HUMAN GENET BRANCH, HUMAN BIOCHEM GENET SECT, BETHESDA, MD 20892 USA. NR 20 TC 13 Z9 13 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1991 VL 198 IS 2 BP 368 EP 374 DI 10.1016/0003-2697(91)90441-U PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GL766 UT WOS:A1991GL76600026 PM 1799224 ER PT J AU HUH, NW BERKOWITZ, P HISKEY, RG PEDERSEN, LG AF HUH, NW BERKOWITZ, P HISKEY, RG PEDERSEN, LG TI DETERMINATION OF STRONTIUM BINDING TO MACROMOLECULES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BOVINE PROTHROMBIN FRAGMENT-1; MG(II); CA(II); IONS C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27514. NIEHS,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-20161, HL-27995] NR 16 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1991 VL 198 IS 2 BP 391 EP 393 DI 10.1016/0003-2697(91)90445-Y PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GL766 UT WOS:A1991GL76600030 PM 1799227 ER PT J AU PALESTINE, AG POLIS, MA DESMET, MD BAIRD, BF FALLOON, J KOVACS, JA DAVEY, RT ZURLO, JJ ZUNICH, KM DAVIS, M HUBBARD, L BROTHERS, R FERRIS, FL CHEW, E DAVIS, JL RUBIN, BI MELLOW, SD METCALF, JA MANISCHEWITZ, J MINOR, JR NUSSENBLATT, RB MASUR, H LANE, HC AF PALESTINE, AG POLIS, MA DESMET, MD BAIRD, BF FALLOON, J KOVACS, JA DAVEY, RT ZURLO, JJ ZUNICH, KM DAVIS, M HUBBARD, L BROTHERS, R FERRIS, FL CHEW, E DAVIS, JL RUBIN, BI MELLOW, SD METCALF, JA MANISCHEWITZ, J MINOR, JR NUSSENBLATT, RB MASUR, H LANE, HC TI A RANDOMIZED, CONTROLLED TRIAL OF FOSCARNET IN THE TREATMENT OF CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH AIDS SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; VIRUS RETINITIS; PHOSPHONOFORMATE FOSCARNET; REPLICATION INVITRO; GANCICLOVIR; DISEASE; INHIBITION; INFECTIONS; ZIDOVUDINE AB Objective: To evaluate foscarnet sodium in treating cytomegalovirus retinitis in patients with AIDS. Patients: Twenty-four previously untreated persons with AIDS and cytomegalovirus retinitis who were at low risk for loss of their visual acuity. Intervention: Patients were randomly assigned to receive either no therapy (delayed treatment, control group) or immediate treatment with intravenous foscarnet at a dose of 60 mg/kg body weight three times a day for 3 weeks (induction regimen) followed by a maintenance regimen of 90 mg/kg once a day. Measurements: Patients were examined weekly until they reached the primary clinical end point, defined as progression of their retinitis border by 750-mu-m or the development of a new retinal lesion due to cytomegalovirus. Progression was evaluated using retinal photographs by masked readers. Secondary evaluations included changes in visual acuity, cytomegalovirus shedding in the blood and urine, serum levels of human immunodeficiency virus type 1 (HIV-1) p24 antigen, and total CD4 T lymphocyte counts. Results: The mean time to progression of retinitis was 3.2 weeks in the control group (n = 11) compared with 13.3 weeks in the treatment group (n = 13) (P < 0.001). Nine of 13 patients in the treatment group had positive blood cultures for cytomegalovirus at entry and all nine cleared their blood of cytomegalovirus by the end of the induction period (P = 0.004) compared with one of six patients in the control group. No reductions in p24 levels were seen in the control patients compared with a reduction of more than 50% in p24 levels for all four patients on treatment for whom follow-up levels were available. The main adverse effects of foscarnet treatment were seizures (2 of 13 patients), hypomagnesemia (9 of 13), hypocalcemia (11 of 13), and elevations in serum creatinine above 176.8-mu-mol/L (2.0 mg/dL) (3 of 13). The control patients received an average of 0.2 units of blood per week compared with an average of 0.6 units of blood per week for the patients on treatment. Conclusions: The administration of foscarnet decreases the rate of progression of cytomegalovirus retinitis in persons with AIDS. Its judicious use is likely to prevent loss of vision in these patients. In this study, however, there was little change in visual acuity in patients in either the immediate or delayed treatment group because only patients with non-sight-threatening disease were selected. C1 NIAID,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. UNIV WISCONSIN,MADISON,WI 53706. OI Polis, Michael/0000-0002-9151-2268; de Smet, Marc/0000-0002-9217-5603 NR 31 TC 271 Z9 274 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1991 VL 115 IS 9 BP 665 EP 673 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA GL697 UT WOS:A1991GL69700001 PM 1656826 ER PT J AU SHINDO, M DIBISCEGLIE, AM CHEUNG, L SHIH, JWK CRISTIANO, K FEINSTONE, SM HOOFNAGLE, JH AF SHINDO, M DIBISCEGLIE, AM CHEUNG, L SHIH, JWK CRISTIANO, K FEINSTONE, SM HOOFNAGLE, JH TI DECREASE IN SERUM HEPATITIS-C VIRAL-RNA DURING ALPHA-INTERFERON THERAPY FOR CHRONIC HEPATITIS-C SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; NON-A; CONTROLLED TRIAL; BLOOD-DONORS; VIRUS; ANTIBODIES; SEQUENCES; GENOME; ALFA AB Objective: To assess the effect of alpha-interferon therapy on hepatitis C viral RNA in serum of patients with chronic hepatitis C. Design: Retrospective testing for hepatitis C viral (HCV) RNA and antibody to the hepatitis C virus (anti-HCV) of stored serum samples from a randomized, double-blind, placebo-controlled trial of alpha-interferon therapy. Setting: Warren Grant Magnuson Clinical Center of the National Institutes of Health, a tertiary referral center. Patients: Forty-one patients with chronic non-A, non-B hepatitis were entered in this trial. Interventions: Twenty-one patients were treated with alpha-interferon, and 20 patients were treated with placebo for 6 months. Seventeen placebo recipients were then treated with alpha-interferon for up to 1 year. Methods: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Titers of both antibody and RNA were determined by serial end-point dilution. Main Results: At entry into the trial, 37 (90%) of 41 patients had anti-HCV and 39 (95%) had HCV RNA in serum. Anti-HCV titers decreased slightly with treatment. Serum levels of HCV RNA decreased in all patients who responded to alpha-interferon therapy with improvements in serum aminotransferases; in 17 of 21 responders (81%; 95% CI, 58% to 95%) HCV RNA became undetectable. In contrast, in only 2 of 16 (12%; CI, 2% to 38%) patients who did not respond to treatment did HCV RNA become undetectable. In 19 patients treated during the preliminary 6-month period with placebo, HCV RNA remained detectable. Finally, in the 11 patients who relapsed when treatment was stopped, HCV RNA reappeared in the serum, but in 4 of 7 patients with a sustained improvement in serum aminotransferases, HCV RNA remained undetectable. Conclusions: These results indicate that the clinical and serum biochemical response to alpha-interferon in chronic hepatitis C is associated with a loss of detectable HCV genome from serum. C1 US FDA,ROCKVILLE,MD 20857. RP SHINDO, M (reprint author), NIH,LIVER DIS SECT,BLD 10,ROOM 4D52,BETHESDA,MD 20892, USA. RI Yang, Chen/G-1379-2010 NR 19 TC 389 Z9 392 U1 1 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1991 VL 115 IS 9 BP 700 EP 704 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GL697 UT WOS:A1991GL69700006 PM 1656828 ER PT J AU IHDE, DC AF IHDE, DC TI CHEMOTHERAPY COMBINED WITH CHEST IRRADIATION FOR LOCALLY ADVANCED NON-SMALL CELL LUNG-CANCER - THE END OF THE BEGINNING SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID THERAPY ONCOLOGY GROUP; RADIATION-THERAPY; RANDOMIZED TRIAL; CARCINOMA; RADIOTHERAPY; SURVIVAL RP IHDE, DC (reprint author), NCI,OFF DIRECTOR,BLDG 31,ROOM 11A48,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1991 VL 115 IS 9 BP 737 EP 739 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GL697 UT WOS:A1991GL69700013 PM 1656829 ER PT J AU PASS, HI AF PASS, HI TI BRONCHIAL ADENOMA - KEY REFERENCES SO ANNALS OF THORACIC SURGERY LA English DT Bibliography RP PASS, HI (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20805, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1991 VL 52 IS 5 BP 1201 EP 1203 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA GP868 UT WOS:A1991GP86800041 PM 1953155 ER PT J AU KORVICK, JA YU, VL AF KORVICK, JA YU, VL TI ANTIMICROBIAL AGENT THERAPY FOR PSEUDOMONAS-AERUGINOSA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID GRANULOCYTOPENIC CANCER-PATIENTS; BETA-LACTAM ANTIBIOTICS; NEGATIVE BACILLARY OSTEOMYELITIS; RESPIRATORY-TRACT INFECTIONS; ORAL CIPROFLOXACIN THERAPY; MALIGNANT EXTERNAL OTITIS; NEUTROPENIC RATS; COMBINATIONS INVITRO; IMIPENEM THERAPY; DOUBLE-BLIND C1 UNIV PITTSBURGH,SCH MED,SCAIFE 968,PITTSBURGH,PA 15261. NIGMS,BETHESDA,MD 20892. VET ADM MED CTR,PITTSBURGH,PA 15206. NR 93 TC 58 Z9 58 U1 1 U2 3 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 NOV PY 1991 VL 35 IS 11 BP 2167 EP 2172 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA GM872 UT WOS:A1991GM87200001 PM 1803987 ER PT J AU FRIEDMAN, RB ROBINSON, SR AF FRIEDMAN, RB ROBINSON, SR TI WHOLE-WORD TRAINING THERAPY IN A STABLE SURFACE ALEXIC PATIENT - IT WORKS SO APHASIOLOGY LA English DT Article ID READING ALOUD; ACTIVATION AB An experimental therapy which focuses on whole-word reading was developed for trial with a surface alexic patient whose reading deficit had been stable for several years. The patient practised reading a group of words with ambiguous vowels. A control group of words with the same ambiguous vowels were never studied but were tested at each session. The patient's reading of the studied words improved steadily over the training sessions. Performance on the control words varied considerably throughout the study. It is concluded that impaired access to orthographic entries in the lexicon can be repaired with practice, but that generalization to similar words is more difficult to achieve. C1 GEORGE WASHINGTON UNIV,DEPT SPEECH & HEARING,WASHINGTON,DC 20052. RP FRIEDMAN, RB (reprint author), NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BLDG 10 RM 5C-422,BETHESDA,MD 20892, USA. NR 13 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD NOV-DEC PY 1991 VL 5 IS 6 BP 521 EP 527 DI 10.1080/02687039108248557 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA GY405 UT WOS:A1991GY40500003 ER PT J AU SHEA, C NUNLEY, JW WILLIAMSON, JC SMITHSOMERVILLE, HE AF SHEA, C NUNLEY, JW WILLIAMSON, JC SMITHSOMERVILLE, HE TI COMPARISON OF THE ADHESION PROPERTIES OF DELEYA-MARINA AND THE EXOPOLYSACCHARIDE-DEFECTIVE MUTANT STRAIN DMR SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SOLID-SURFACES; BACTERIA; ATTACHMENT; HYDROPHOBICITY; SUBSTRATUM; MECHANISM; LARVAE; ASSAY; NOV AB Deleya marina 219 (ATCC 25374) produces large quantities of an acidic exopolysaccharide and characteristically forms mucoid colonies and large aggregates of cells. The exopolysaccharide of wild-type D. marina cells appears to occur as both film and fibrils in electron micrographs. The organization of exopolymeric material was indicative of structural heterogeneity. A spontaneous rough-colony mutant defective in exopolysaccharide, D. marina DMR, has been isolated. The absence of exopolymer corresponds to a nonmucoid, nonaggregating, adhesion-altered phenotype. In microplate adhesion assays, wild-type cells grown at 19 or 25-degrees-C attached to hydrophilic surfaces but not to a hydrophobic surface. In contrast, mutant cells exhibited a significantly reduced level of attachment to hydrophilic surfaces and increased adhesion to a hydrophobic surface. C1 TENNESSEE VALLEY AUTHOR,BIOTECH RES DEPT,CEB 1C,MUSCLE SHOALS,AL 35660. NCI,PROGRAM RESOURCES INC,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. RP SHEA, C (reprint author), UNIV ALABAMA,DEPT BIOL SCI,TUSCALOOSA,AL 35487, USA. NR 32 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 1991 VL 57 IS 11 BP 3107 EP 3113 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA GN265 UT WOS:A1991GN26500008 PM 1781675 ER PT J AU SCHOOLER, C AF SCHOOLER, C TI ON INTELLIGENCE ... MORE-OR-LESS - A BIOECOLOGICAL TREATISE ON INTELLECTUAL-DEVELOPMENT - CECI,SJ SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Book Review RP SCHOOLER, C (reprint author), NIMH,SOCIOENVIRONM STUDIES LAB,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD NOV-DEC PY 1991 VL 5 IS 6 BP 532 EP 534 DI 10.1002/acp.2350050611 PG 3 WC Psychology, Experimental SC Psychology GA GX051 UT WOS:A1991GX05100010 ER PT J AU WEBER, DN RUSSO, A SEALE, DB SPIELER, RE AF WEBER, DN RUSSO, A SEALE, DB SPIELER, RE TI WATERBORNE LEAD AFFECTS FEEDING ABILITIES AND NEUROTRANSMITTER LEVELS OF JUVENILE FATHEAD MINNOWS (PIMEPHALES-PROMELAS) SO AQUATIC TOXICOLOGY LA English DT Article DE LEAD TOXICITY; FEEDING BEHAVIOR; NOREPINEPHRINE; SEROTONIN; DOPAMINE; METAL TOXICITY ID TROUT SALVELINUS-FONTINALIS; LARGEMOUTH BASS; SALMO-GAIRDNERI; EXPOSURE; BEHAVIOR; EXPERIENCE; PREDATION; CADMIUM AB Fathead minnows (Pimephales promelas) were exposed for a total of 4 wk to 0, 0.5 or 1.0 mg/l lead as lead acetate. After 14-day acclimation to flake food, separate groups were fed either 20 1-day, 2-day or 7-day old Daphnia magna on alternate days for 14 days and tested for total time spent feeding, failed attempts and foraging distance. Time spent feeding on daphnids and number of miscues were significantly higher among lead-exposed groups than in control fish (P < 0.05). Except for a high significance among fish exposed to 1.0 mg/l lead and feeding on the largest sized prey (7-day olds), reaction distance showed no dose-response. After 4 wk, body lead ranged from not detectable in the controls to 44.2 +/- 2.5 mg/l in the 1.0 mg/l lead exposed groups. Examination of whole brain neurotransmitters indicated a significant increase in both serotonin and norepinephrine levels (P < 0.01) but no change in dopamine in response to lead intoxication. C1 CALIF STATE UNIV LONG BEACH,DEPT PHYS THERAPY,LONG BEACH,CA 90840. UNIV WISCONSIN,DEPT BIOL SCI,MILWAUKEE,WI 53201. MILWAUKEE PUBL MUSEUM,DIV VERTEBRATE ZOOL,MILWAUKEE,WI 53233. RP WEBER, DN (reprint author), UNIV WISCONSIN,NIEHS,MARINE & FRESHWATER BIOMED RES CTR,MILWAUKEE,WI 53201, USA. NR 38 TC 43 Z9 44 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD NOV PY 1991 VL 21 IS 1-2 BP 71 EP 80 DI 10.1016/0166-445X(91)90006-U PG 10 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA GR906 UT WOS:A1991GR90600005 ER PT J AU TAKAHASHI, N LIAPI, C ANDERSON, WB BREITMAN, TR AF TAKAHASHI, N LIAPI, C ANDERSON, WB BREITMAN, TR TI RETINOYLATION OF THE CAMP-BINDING REGULATORY SUBUNITS OF TYPE-I AND TYPE-II CAMP-DEPENDENT PROTEIN-KINASES IN HL-60-CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID RECEPTOR; ADENOSINE 3'-5'-MONOPHOSPHATE-INDUCING AGENTS; EMBRYONAL CARCINOMA-CELLS; INDUCED DIFFERENTIATION; SUBCELLULAR-DISTRIBUTION; FATTY ACYLATION; DIBUTYRYL-CAMP; PHORBOL ESTER; HL-60 CELLS C1 NCI,DIV CANC BIOL & DIAG,CELLULAR ONCOL LAB,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 71 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1991 VL 290 IS 2 BP 293 EP 302 DI 10.1016/0003-9861(91)90544-S PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GK751 UT WOS:A1991GK75100005 PM 1656875 ER PT J AU KLEINMAN, HK WEEKS, BS CANNON, FB SWEENEY, TM SEPHEL, GC CLEMENT, B ZAIN, M OLSON, MOJ JUCKER, M BURROUS, BA AF KLEINMAN, HK WEEKS, BS CANNON, FB SWEENEY, TM SEPHEL, GC CLEMENT, B ZAIN, M OLSON, MOJ JUCKER, M BURROUS, BA TI IDENTIFICATION OF A 110-KDA NONINTEGRIN CELL-SURFACE LAMININ-BINDING PROTEIN WHICH RECOGNIZES AN A CHAIN NEURITE-PROMOTING PEPTIDE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID AMINO-ACID-SEQUENCE; A-CHAIN; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDE; PHOSPHOPROTEIN PP-105; RECEPTOR; ATTACHMENT; MEMBRANES; MIGRATION; GLYCOPROTEIN C1 VANDERBILT UNIV,SCH MED,LAB SERV,NASHVILLE,TN 37203. HOSP PONTCHAILLOU,INSERM,U49,F-35033 RENNES,FRANCE. UNIV MISSISSIPPI,MED CTR,DEPT BIOCHEM,JACKSON,MS 39216. NIA,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. US PATENT & TRADEMARK OFF,ARLINGTON,VA 22202. RP KLEINMAN, HK (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 407,BETHESDA,MD 20892, USA. RI Clement, Bruno/E-5546-2016 FU NIGMS NIH HHS [R01 GM28349] NR 48 TC 111 Z9 113 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1991 VL 290 IS 2 BP 320 EP 325 DI 10.1016/0003-9861(91)90547-V PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GK751 UT WOS:A1991GK75100008 PM 1834017 ER PT J AU WEINBERGER, DR JONES, DW COPPOLA, R BERMAN, KF GIBSON, R REBA, RC AF WEINBERGER, DR JONES, DW COPPOLA, R BERMAN, KF GIBSON, R REBA, RC TI CONCERNING THE DISTRIBUTION OF CEREBRAL MUSCARINIC ACETYLCHOLINE-RECEPTORS IN ALZHEIMERS-DISEASE - REPLY SO ARCHIVES OF NEUROLOGY LA English DT Letter RP WEINBERGER, DR (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1991 VL 48 IS 11 BP 1118 EP 1118 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA GP074 UT WOS:A1991GP07400002 ER PT J AU KAISERKUPFER, MI CARUSO, RC VALLE, D AF KAISERKUPFER, MI CARUSO, RC VALLE, D TI GYRATE ATROPHY OF THE CHOROID AND RETINA - LONG-TERM REDUCTION OF ORNITHINE SLOWS RETINAL DEGENERATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FOLLOW-UP; ARGININE; HYPERORNITHINEMIA; VITAMIN-B6; CREATINE; MUTATION; PROTEIN; TRIAL; ACID; DIET AB Gyrate atrophy of the choroid and retina is an autosomal recessive, chorioretinal dystrophy that begins in childhood and leads to blindness in the fourth to seventh decade of life. The primary defect is deficiency of ornithine-delta-aminotransferase, which results in accumulation of ornithine. We examined six pairs of affected siblings to determine if intrafamilial variability in the phenotype was less than interfamilial, and to determine if long-term (5- to 7-year) reduction of ornithine with an arginine-restricted diet had an effect on the progression of the chorioretinal degeneration. All but one set of siblings underwent periodic ophthalmologic examinations. The clinical diagnosis was confirmed with the demonstration of hyperornithinemia and deficiency of ornithine-delta-aminotransferase. The molecular defects in their ornithine-delta-aminotransferase genes also were determined. The two younger pairs of siblings were given an arginine-restricted diet and followed up for 5 to 7 years. We found strikingly similar phenotypes in affected members of the same pair of siblings. In the young patients receiving the diet, there was substantial reduction of ornithine levels. These children had only modest progression of their ocular disease during this period. Furthermore, a comparison of the outcome of the younger with their older siblings at an equivalent age showed that the younger siblings, who started receiving the diet at an earlier age, had much less ocular disease. We conclude that intrafamilial phenotypic variation in gyrate atrophy is less than interfamilial and, therefore, that genetic heterogeneity plays a role in the phenotypic variability of gyrate atrophy. Furthermore, we conclude that chronic reduction of ornithine with an arginine-restricted diet dramatically slows the progression of the chorioretinal dystrophy. C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST LAB GENET,BALTIMORE,MD 21205. RP KAISERKUPFER, MI (reprint author), NEI,9000 ROCKVILLE PIKE 10 10N226,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-00052]; NEI NIH HHS [2RO1 EY02948] NR 36 TC 49 Z9 49 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 1991 VL 109 IS 11 BP 1539 EP 1548 PG 10 WC Ophthalmology SC Ophthalmology GA GP106 UT WOS:A1991GP10600033 PM 1755734 ER PT J AU AXIOTIS, CA AF AXIOTIS, CA TI PAPILLARY ENDOTHELIAL HYPERPLASIA IN THE THYROID - REPLY SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter RP AXIOTIS, CA (reprint author), NCI,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1991 VL 115 IS 11 BP 1088 EP 1088 PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA GN261 UT WOS:A1991GN26100002 ER PT J AU LEFF, RL BURGESS, SH MILLER, FW LOVE, LA TARGOFF, IN DALAKAS, MC JOFFE, MM PLOTZ, PH AF LEFF, RL BURGESS, SH MILLER, FW LOVE, LA TARGOFF, IN DALAKAS, MC JOFFE, MM PLOTZ, PH TI DISTINCT SEASONAL PATTERNS IN THE ONSET OF ADULT IDIOPATHIC INFLAMMATORY MYOPATHY IN PATIENTS WITH ANTI-JO-1 AND ANTI-SIGNAL RECOGNITION PARTICLE AUTOANTIBODIES SO ARTHRITIS AND RHEUMATISM LA English DT Note ID POLYMYOSITIS DERMATOMYOSITIS; MYOSITIS; ANTIBODIES AB In idiopathic inflammatory myopathy (IIM; or, polymyositis/dermatomyositis), the myositis-specific autoantibodies anti-Jo-1 and anti-signal recognition particle (anti-SRP), appear to define clinically and immunogenetically distinct groups of patients. We show here that the month during which the onset of weakness occurs is not random in patients with anti-Jo-1 autoantibodies (average month April, P < 0.02) and in those with anti-SRP autoantibodies (average month November, P < 0.02); both groups of patients also experience rapid onset of disease. By contrast, patients classified into the traditional categories of polymyositis and dermatomyositis do not have recognizable seasonal patterns and do not differ in the rate of onset of disease. These findings suggest that searches for seasonal patterns in the onset of autoimmune disorders characterized by disease-specific autoantibodies may provide useful clues to etiology. RP LEFF, RL (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-27181]; NIAMS NIH HHS [AR-32214] NR 18 TC 71 Z9 72 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1991 VL 34 IS 11 BP 1391 EP 1396 PG 6 WC Rheumatology SC Rheumatology GA GN259 UT WOS:A1991GN25900007 PM 1953817 ER PT J AU KLINMAN, DM SHIRAI, A ISHIGATSUBO, Y CONOVER, J STEINBERG, AD AF KLINMAN, DM SHIRAI, A ISHIGATSUBO, Y CONOVER, J STEINBERG, AD TI QUANTITATION OF IGM-SECRETING AND IGG-SECRETING B-CELLS IN THE PERIPHERAL-BLOOD OF PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTIBODY-FORMING-CELLS; DNA ANTIBODIES; AUTOIMMUNE-DISEASE; HUMAN-SERA; MICE; AUTOANTIBODIES; LYMPHOCYTES; ACTIVATION; ANTIGENS; SLE AB An enzyme-linked immunospot assay was used to quantitate the number of autoantibody-secreting B cells in the peripheral blood of 67 patients with systemic lupus erythematosus. These patients had 1.5-4-fold more lymphocytes secreting IgG and IgM per million peripheral blood lymphocytes than did normal controls. There was a concomitant increase in the number of B cells secreting antibodies reactive with a diverse panel of foreign and self antigens (including actin, myosin, trinitrophenylated keyhole limpet hemocyanin, ovalbumin, and retroviral gp160). By comparison, the number of B cells producing anti-DNA antibodies was increased disproportionately. The magnitude of this anti-DNA response correlated significantly with disease activity. Thus, B cell activation in human systemic lupus erythematosus had characteristics of both generalized (polyclonal) B cell activation and (auto)antigen-specific immune stimulation. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD. YOKOHAMA CITY UNIV,SCH MED,YOKOHAMA,KANAGAWA 232,JAPAN. RP KLINMAN, DM (reprint author), US FDA,CBER,DIV VIROL,RETROVIRUS RES LAB,BLDG 29A,ROOM 3 D 02,BETHESDA,MD 20892, USA. NR 41 TC 52 Z9 52 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1991 VL 34 IS 11 BP 1404 EP 1410 PG 7 WC Rheumatology SC Rheumatology GA GN259 UT WOS:A1991GN25900009 PM 1719987 ER PT J AU HOFFMAN, GS FILIE, JD SCHUMACHER, HR ORTIZBRAVO, E TSOKOS, MG MARINI, JC KERR, GS LING, QH TRENTHAM, DE AF HOFFMAN, GS FILIE, JD SCHUMACHER, HR ORTIZBRAVO, E TSOKOS, MG MARINI, JC KERR, GS LING, QH TRENTHAM, DE TI INTRACTABLE VASCULITIS, RESORPTIVE OSTEOLYSIS, AND IMMUNITY TO TYPE-I COLLAGEN IN TYPE-VIII EHLERS-DANLOS SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OSTEOGENESIS IMPERFECTA; ARTHRITOGENIC FACTOR; CONTRACTURES; PROCOLLAGEN; FIBROBLASTS; ARTHRITIS; DIGESTION; LIGHT AB A unique patient with type VIII Ehlers-Danlos syndrome and cutaneous vasculitis, resorptive osteolysis, and cardiac valvular disease is described. Collagen analyses identified morphologic and physical abnormalities of type I collagen. The patient's T lymphocytes could be propagated in vitro with type I collagen and produced a 60-kd lymphokine that bound this protein. Cellular autoimmunity to type I collagen may be responsible for this patient's intractable clinical condition. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV PENN,VET ADM MED CTR,SCH MED,CTR ARTHRIT IMMUNOL,PHILADELPHIA,PA 19104. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215. RP HOFFMAN, GS (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 35 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1991 VL 34 IS 11 BP 1466 EP 1475 PG 10 WC Rheumatology SC Rheumatology GA GN259 UT WOS:A1991GN25900018 PM 1953824 ER PT J AU PATTI, L SWINBURN, B RICCARDI, G RIVELLESE, AA HOWARD, BV AF PATTI, L SWINBURN, B RICCARDI, G RIVELLESE, AA HOWARD, BV TI ALTERATIONS IN VERY LOW-DENSITY-LIPOPROTEIN SUBFRACTIONS IN NORMOTRIGLYCERIDEMIC NON-INSULIN-DEPENDENT DIABETICS SO ATHEROSCLEROSIS LA English DT Article DE ATHEROSCLEROSIS; VLDL, VLDL SUBFRACTIONS; DIABETES; LIPOPROTEIN COMPOSITION ID VERY-LOW-DENSITY; APOLIPOPROTEIN-B; PLASMA; METABOLISM; TRIGLYCERIDE; CHOLESTEROL; MELLITUS AB Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in S(f) value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (S(f) > 400), B (S(f) 175-400), C (S(f) 100-175), and D (S(f) 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P < 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P < 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P < 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P < 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P < 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic. C1 NIH,BETHESDA,MD 20892. MEDLANTIC RES FDN,WASHINGTON,DC. RP PATTI, L (reprint author), NAPLES UNIV,SCH MED 2,INST INTERNAL MED & METAB DIS,VIA S PANSINI 5,I-80131 NAPLES,ITALY. RI riccardi, gabriele/A-9269-2012 NR 37 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 1991 VL 91 IS 1-2 BP 15 EP 23 DI 10.1016/0021-9150(91)90183-4 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GT887 UT WOS:A1991GT88700002 PM 1811550 ER PT J AU LAMONFAVA, S JIMENEZ, D CHRISTIAN, JC FABSITZ, RR REED, T CARMELLI, D CASTELLI, WP ORDOVAS, JM WILSON, PWF SCHAEFER, EJ AF LAMONFAVA, S JIMENEZ, D CHRISTIAN, JC FABSITZ, RR REED, T CARMELLI, D CASTELLI, WP ORDOVAS, JM WILSON, PWF SCHAEFER, EJ TI THE NHLBI TWIN STUDY - HERITABILITY OF APOLIPOPROTEIN-A-I, APOLIPOPROTEIN-B, AND LOW-DENSITY-LIPOPROTEIN SUBCLASSES AND CONCORDANCE FOR LIPOPROTEIN(A) SO ATHEROSCLEROSIS LA English DT Article DE APOLIPOPROTEIN-A-I; APOLIPOPROTEIN-B; LOW DENSITY LIPOPROTEIN; LIPOPROTEIN(A); TWINS; HERITABILITY; CORONARY ARTERY DISEASE ID CORONARY-ARTERY DISEASE; COMPLEX SEGREGATION ANALYSIS; MYOCARDIAL-INFARCTION; GENETIC VARIANCE; HEART-DISEASE; CHOLESTEROL CONCENTRATIONS; PREMATURE ATHEROSCLEROSIS; PLASMA-CHOLESTEROL; LP(A) LIPOPROTEIN; RISK-FACTORS AB Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P < 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P < 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P < 0.0001), body mass index (BMI, P < 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P < 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P < 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twins pairs, were discordant for elevated lipoprotein(a) on gradient gels (P < 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample. C1 TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,LIPID METAB LAB,711 WASHINGTON ST,BOSTON,MA 02111. INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46202. SRI INT,MENLO PK,CA 94025. NHLBI,DIV HEART & VASC DIS,CLIN & GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,EPIDEMIOL & BIOMETRY PROGRAM,FRAMINGHAM,MA. FU NHLBI NIH HHS [HL35243, N0 I-HC-55027] NR 52 TC 96 Z9 96 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 1991 VL 91 IS 1-2 BP 97 EP 106 DI 10.1016/0021-9150(91)90191-5 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GT887 UT WOS:A1991GT88700010 PM 1839820 ER PT J AU AOTA, S NAGAI, T OLDEN, K AKIYAMA, SK YAMADA, KM AF AOTA, S NAGAI, T OLDEN, K AKIYAMA, SK YAMADA, KM TI FIBRONECTIN AND INTEGRINS IN CELL-ADHESION AND MIGRATION SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 639TH MEETING OF THE BIOCHEMICAL SOC CY JUL 16-19, 1991 CL MANCHESTER UNIV, MANCHESTER, ENGLAND SP BIOCHEM SOC HO MANCHESTER UNIV ID RECEPTOR; FRAGMENTS; SITE; MUTAGENESIS; ATTACHMENT; SIGNAL C1 HOWARD UNIV,CTR CANC,WASHINGTON,DC 20060. RP AOTA, S (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 35 TC 23 Z9 23 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1991 VL 19 IS 4 BP 830 EP 835 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV019 UT WOS:A1991GV01900008 PM 1794567 ER PT J AU CHOCHUNG, YS NESTEROVA, MV SEVERIN, ES VINOGRADOV, SV AF CHOCHUNG, YS NESTEROVA, MV SEVERIN, ES VINOGRADOV, SV TI CHEMICAL MODIFICATION ENHANCES THE INHIBITORY EFFECT OF REGULATORY SUBUNIT ANTISENSE OLIGODEOXYNUCLEOTIDE OF CAMP-DEPENDENT PROTEIN-KINASE TYPE-I ON CELL-PROLIFERATION SO BIOCHEMISTRY INTERNATIONAL LA English DT Article ID INFLUENZA-VIRUS; DIFFERENTIATION; REPRODUCTION C1 RES CTR MOLEC DIAGNOST & THERAPY,MOSCOW 113149,RUSSIA. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 15 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 0158-5231 J9 BIOCHEM INT PD NOV PY 1991 VL 25 IS 4 BP 767 EP 773 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA614 UT WOS:A1991HA61400019 PM 1667721 ER PT J AU FAROOQUI, F SARIN, PS SUN, D LETSINGER, RL AF FAROOQUI, F SARIN, PS SUN, D LETSINGER, RL TI EFFECT OF STRUCTURAL VARIATIONS IN CHOLESTERYL-CONJUGATED OLIGONUCLEOTIDES ON INHIBITORY ACTIVITY TOWARD HIV-1 SO BIOCONJUGATE CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CHRONICALLY INFECTED-CELLS; PHOSPHOROTHIOATE ANALOGS; OLIGODEOXYNUCLEOTIDES; REPLICATION AB A number of oligonucleotide analogues containing internucleoside phosphorothioate linkages and a covalently attached cholesteryl residue was synthesized and tested for activity against HIV-1 in cultures of Molt3 cells. Structural features important for high antiviral activity are the presence of a cholesteryl moiety, a run of terminal phosphorothioate groups, and the presence of nucleoside residues. An increase in length of the tether between cholesteryl and phosphorus from six to 14 atoms has no significant effect on antiviral activity, and up to one-half of the internucleoside links in a cholesteryl-conjugated phosphorothioate oligomer and one-third of the internucleoside links in a nonconjugated phosphorothioate can be replaced with phosphodiester links without much change in antiviral activity. However, replacement of nucleoside units in the oligomers by a simple analogue (-OCH2CH2CH2O-) yields inactive or very weakly active compounds, even in the presence of a cholesteryl group. Dose-response patterns for assays in which cholesteryl-conjugated oligomers are added to test cells either simultaneously or subsequently to viral infection are similar for homooligomer derivatives and for oligomers containing "antisense" sequences, suggesting a similarity in mode of action for the two classes of oligomers in this system. C1 NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC & CELL BIOL,EVANSTON,IL 60208. GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP FAROOQUI, F (reprint author), NORTHWESTERN UNIV,DEPT CHEM,EVANSTON,IL 60208, USA. FU NIAID NIH HHS [U OI AI24846] NR 10 TC 15 Z9 15 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1991 VL 2 IS 6 BP 422 EP 426 DI 10.1021/bc00012a007 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GR937 UT WOS:A1991GR93700007 PM 1805939 ER PT J AU INMAN, JK HIGHET, PF KOLODNY, N ROBEY, FA AF INMAN, JK HIGHET, PF KOLODNY, N ROBEY, FA TI SYNTHESIS OF N-ALPHA-(TERT-BUTOXYCARBONYL)-N-EPSILON-[N-(BROMOACETYL)-BETA-ALANYL]-L- LYSINE - ITS USE IN PEPTIDE-SYNTHESIS FOR PLACING A BROMOACETYL CROSS-LINKING FUNCTION AT ANY DESIRED SEQUENCE POSITION SO BIOCONJUGATE CHEMISTRY LA English DT Note ID PROTEIN CONJUGATION; AUTOMATED SYNTHESIS; VACCINE DESIGN; IMMUNOGENS; MANIPULATION; POLYMERS; BINDING; CELL AB A new amino acid derivative, N(alpha)-(tert-butoxycarbonyl)-N(epsilon)-[N-(bromoacetyl)-beta-alanyl]-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates, and polymers. BBAL is synthesized by condensation of N-bromoacetyl-beta-alanine with N(alpha)-Boc-L-lysine and is a white powder which is readily stored, weighed, and used with a peptide synthesizer, programmed for N(alpha)-Boc amino acid derivatives. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers, also linked through thioether bonds. Products made with BBAL peptides maybe characterized by amino acid analysis of acid hydrolyzates by quantification of beta-alanine, which separates from natural amino acids in suitable analytical systems. Where sulfhydryl groups on coupling partners arise from cysteine residues, S-(carboxymethyl)cysteine in acid hydrolyzates may also be assayed for this purpose. Examples are given of the use of BBAL in preparing peptide polymers and a peptide conjugate with bovine albumin to serve as immunogens or model vaccine components. C1 NIDR,CELLULAR DEV & ONCOL LAB,PEPTIDE & IMMUNOCHEM UNIT,BETHESDA,MD 20892. RP INMAN, JK (reprint author), NIAID,IMMUNOL LAB,BIOORGAN CHEM SECT,BETHESDA,MD 20892, USA. NR 27 TC 15 Z9 15 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1991 VL 2 IS 6 BP 458 EP 463 DI 10.1021/bc00012a014 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GR937 UT WOS:A1991GR93700014 PM 1805944 ER PT J AU DICKSON, RB GOTTARDIS, MM MERLINO, GT AF DICKSON, RB GOTTARDIS, MM MERLINO, GT TI MOLECULAR INSIGHTS INTO BREAST-CANCER FROM TRANSGENIC MOUSE MODELS SO BIOESSAYS LA English DT Review ID MAMMARY EPITHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR; C-MYC; FACTOR-BETA; TGF-ALPHA; HA-RAS; ATAXIA-TELANGIECTASIA; GENE-EXPRESSION; FACTOR RECEPTOR; EGF RECEPTOR AB We desperately need to know more of the biological details of the onset and progression of breast cancer. The disease is of startlingly high incidence (approaching 1 in 9 women), our current therapies for the disease are inadequate once it has metastasized, and the disease is characterized by excessive morbidity and mortality. Most of the growth and differentiation of the mammary gland occurs relatively late in life: during sexual maturation, and then cyclically during pregnancy and lactation. Normal as well as malignant growth is regulated by endocrine hormones as well as by local tissue factors, such as polypeptide growth factors. Cancer seems to progress as hyperplastic ductal or lobular epithelial growth, acquiring progressive genetic changes (including those of oncogenes and tumor suppressor genes) leading to clonal outgrowths of progressively more malignant cells. The nature of proliferative controls and the relevant genetic changes are the subjects of the current review. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20902. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT MED ONCOL,WASHINGTON,DC 20007. RP DICKSON, RB (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT ANAT & CELL BIOL,3800 RESERVOIR RD,WASHINGTON,DC 20007, USA. NR 64 TC 20 Z9 20 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV PY 1991 VL 13 IS 11 BP 591 EP 596 DI 10.1002/bies.950131109 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GR683 UT WOS:A1991GR68300006 PM 1663341 ER PT J AU DANIEL, DG GOLDBERG, TE GIBBONS, RD WEINBERGER, DR AF DANIEL, DG GOLDBERG, TE GIBBONS, RD WEINBERGER, DR TI LACK OF A BIMODAL DISTRIBUTION OF VENTRICULAR SIZE IN SCHIZOPHRENIA - A GAUSSIAN MIXTURE ANALYSIS OF 1056 CASES AND CONTROLS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID NEBRASKA NEUROPSYCHOLOGICAL BATTERY; YOUNG CHRONIC-SCHIZOPHRENICS; COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID; COMPUTED-TOMOGRAPHY; MONOAMINE METABOLITES; CLINICAL-SIGNIFICANCE; NEGATIVE SYMPTOMS; BRAIN ENLARGEMENT; HOMOVANILLIC-ACID AB The finding of clinical and laboratory differences between schizophrenic patients with large and small cerebral ventricles has led to the widespread assumption that large ventricles are a marker that characterizes a subgroup of patients with schizophrenia. We reviewed all published English language ventricle-to-brain ratio (VBR) studies in which individual data points were available (schizophrenics: n = 691, medical controls: n = 205, normal volunteers: n = 160). Using a univariate normal mixture model to examine the distribution of ventricular size in each group, we found no evidence of a mixture of Gaussian distributions (i.e., "bimodality") within any of the three groups. The same analysis was then performed on the combined sample of schizophrenic patients and normal and medical controls, respectively. In each case the improvement in fit of a mixture of normal distributions compared to a single component normal distribution was significant. The data do not support the notion that ventricular enlargement is a discontinuous marker of a subtype of schizophrenia. C1 UNIV ILLINOIS,DEPT BIOSTAT,CHICAGO,IL 60680. UNIV ILLINOIS,DEPT PSYCHIAT,CHICAGO,IL 60680. RP DANIEL, DG (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 78 TC 68 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1991 VL 30 IS 9 BP 887 EP 903 DI 10.1016/0006-3223(91)90003-5 PG 17 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GQ998 UT WOS:A1991GQ99800003 PM 1747437 ER PT J AU BURT, CT CHEN, B HILL, CH AF BURT, CT CHEN, B HILL, CH TI P-31 NMR INVESTIGATION OF VANADIUM-TREATED CHICK MUSCLE SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE PHOSPHORUS NMR; VANADIUM; SERINE ETHANOLAMINE PHOSPHODIESTER; PH; RED AND WHITE MUSCLE ID NUCLEAR MAGNETIC-RESONANCE; PHOSPHORUS AB The phosphorus NMR profile of normal and vanadium-treated chick muscle was obtained in vivo. The data show that the differentiation of breast and thigh muscles in terms of pH, lipid related metabolites, and bioenergetic parameters can be readily followed. Although the vanadium-treated chicks showed substantial retardation of growth, the only NMR parameter that was significantly affected by dietary vanadium was the pH of breast muscle, which was substantially more acidic in the vanadium-treated animals. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. YALE UNIV,DEPT DIAGNOST RADIOL,NEW HAVEN,CT 06510. NR 9 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD NOV PY 1991 VL 31 IS 2 BP 193 EP 198 DI 10.1007/BF02990427 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA GQ045 UT WOS:A1991GQ04500010 PM 9438040 ER PT J AU FLAMION, B BUNGAY, PM GIBSON, CC SPRING, KR AF FLAMION, B BUNGAY, PM GIBSON, CC SPRING, KR TI FLOW-RATE MEASUREMENTS IN ISOLATED PERFUSED KIDNEY-TUBULES BY FLUORESCENCE PHOTOBLEACHING RECOVERY SO BIOPHYSICAL JOURNAL LA English DT Article ID ERYTHROCYTE-MEMBRANES; DIFFUSION; CELLS; MOBILITY; PERMEABILITY; MICROSCOPY; WATER; ACTIN AB We have developed a new application of the fluorescence photobleaching recovery (FPR) technique for instantaneous measurement of volume flow rates at any axial position along isolated perfused kidney tubules. The method requires fast data acquisition of emitted fluorescence through a photomultiplier (time resolution, 0.5 ms) coupled with differential interference contrast microscopy to measure luminal diameters accurately. While the tubule is perfused in vitro with an impermeant fluorophore (fluorescein sulfonate), a 20-ms bleach pulse reduces the fluorescence in the observation region by 20-25%. Fluorescence recovery is a direct function of perfusate velocity; diffusion plays no significant role in the early phase of recovery. A fluid dynamics approach to data analysis shows that fractional recovery increases linearly with time until t = L/2-upsilon(m), where L is the length of the observation window and upsilon(m) is the mean axial velocity. Practically, a linear regression analysis of the early recovery phase allows measurement of upsilon(m) of up to 0.14 cm/s, i.e., a 40-nl/min flow rate in a 25-mu-m-diameter tubule. Calibration experiments in small glass tubes perfused at predetermined flow rates demonstrated good accuracy (within 1 0%) and reproducibility (coefficient of variation, 8.7%). In rat inner medullary collecting ducts microperfused at 4-40 nl/min, the correlation with a standard fluid collection method was excellent (r2 > 0.97). The method should also be suitable for the direct measurement of fluid flow rate in kidney tubules or blood vessels microperfused in vivo. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP FLAMION, B (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 31 TC 20 Z9 20 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1991 VL 60 IS 5 BP 1229 EP 1242 PG 14 WC Biophysics SC Biophysics GA GR685 UT WOS:A1991GR68500022 PM 1760509 ER PT J AU SHERMAN, A RINZEL, J AF SHERMAN, A RINZEL, J TI POLITICS OF PACEMAKER DOMINANCE - A POLITICAL RESPONSE SO BIOPHYSICAL JOURNAL LA English DT Letter RP SHERMAN, A (reprint author), NIDDK,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1991 VL 60 IS 5 BP 1296 EP 1296 PG 1 WC Biophysics SC Biophysics GA GR685 UT WOS:A1991GR68500029 ER PT J AU MAZUR, J JERNIGAN, RL AF MAZUR, J JERNIGAN, RL TI DISTANCE-DEPENDENT DIELECTRIC-CONSTANTS AND THEIR APPLICATION TO DOUBLE-HELICAL DNA SO BIOPOLYMERS LA English DT Article ID B-DNA; ELECTROSTATIC INTERACTIONS; SEQUENCE DEPENDENCE; CONFORMATION; CURVATURE; DODECAMER; DYNAMICS AB Detailed studies of structures of biological macromolecules, even in simplified models, involve many costly and time-consuming calculations. Any thorough methods require sampling of an extremely large conformation and momentum space. Calculations of electrostatic interactions, which depend on many physical factors, such as the details of solvent, solvent accessibility in macromolecules, and molecular polarizability, are always developed in a compromise between more rigorous, detailed models and the need for immediate application to complicated biological systems. In this paper, a middle ground is taken between the more exact theoretical models and the simplest constant values for the dielectric constant. The effects of solvent, counterions, and molecular polarizability are incorporated through a set of adjustable parameters that should be determined from experimental conditions. Several previous forms for the dielectric function are compared with the new ones. The present methods use Langevin functions to span the region of dielectric constant between bulk solvent and cavity values. Application of such dielectric models to double-helical DNA is important because base-stacking preferences were previously demonstrated [A. Sarai, J. Mazur, R. Nussinov, and R. L. Jernigan (1988) Biochemistry, vol. 27, pp. 8498-8502] to be sensitive to the electrostatic formulation. Here we find that poly (dG) . poly (dC) can be A form for high screening and B form for low screening. By contrast, poly (dA) . poly (dT) can only take the B form. Base stacking is more sensitive to the form of the dielectric function than are the sugar-phosphate backbone conformations. Also in B form, the backbone conformations are not so affected by the base types as in A form. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP MAZUR, J (reprint author), PRI DYNCORP,FREDERICK CANC RES FACIL,BLDG 430,FREDERICK,MD 21702, USA. RI Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [N01-CO-74102] NR 30 TC 50 Z9 51 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD NOV PY 1991 VL 31 IS 13 BP 1615 EP 1629 DI 10.1002/bip.360311316 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HA436 UT WOS:A1991HA43600014 PM 1814508 ER PT J AU JACOBSEN, SEW KELLER, JR RUSCETTI, FW KONDAIAH, P ROBERTS, AB FALK, LA AF JACOBSEN, SEW KELLER, JR RUSCETTI, FW KONDAIAH, P ROBERTS, AB FALK, LA TI BIDIRECTIONAL EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ON COLONY-STIMULATING FACTOR-INDUCED HUMAN MYELOPOIESIS INVITRO - DIFFERENTIAL-EFFECTS OF DISTINCT TGF-BETA ISOFORMS SO BLOOD LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; BIFUNCTIONAL REGULATOR; BIOLOGICAL-ACTIVITIES; PROLIFERATION; FACTOR-BETA-1; RECEPTORS; BONE; INTERLEUKIN-3; DETERMINANTS; EXPRESSION C1 NCI, FREDERICK CANC RES & DEV CTR, PRI DYN CORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NCI, CHEMOPROTECT LAB, BETHESDA, MD 20892 USA. RP JACOBSEN, SEW (reprint author), NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 98 Z9 100 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1991 VL 78 IS 9 BP 2239 EP 2247 PG 9 WC Hematology SC Hematology GA GM787 UT WOS:A1991GM78700012 PM 1718492 ER PT J AU HUANG, SZ RODGERS, GP ZENG, FY ZENG, YT SCHECHTER, AN AF HUANG, SZ RODGERS, GP ZENG, FY ZENG, YT SCHECHTER, AN TI DIAGNOSIS OF THALASSEMIA USING CDNA AMPLIFICATION OF CIRCULATING ERYTHROID CELL MESSENGER-RNA WITH THE POLYMERASE CHAIN-REACTION SO BLOOD LA English DT Article ID AMPLIFIED BETA-GLOBIN; PRENATAL-DIAGNOSIS; ENZYMATIC AMPLIFICATION; MOLECULAR-BASIS; DNA; MUTATIONS; HEMOGLOBIN; LEUKEMIA; GENE; QUANTITATION C1 SHANGHAI CHILDRENS HOSP,SHANGHAI INST MED GENET,SHANGHAI,PEOPLES R CHINA. NIDDKD,CHEM BIOL LAB,BETHESDA,MD. FU NHLBI NIH HHS [HLB-29623] NR 35 TC 23 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1991 VL 78 IS 9 BP 2433 EP 2437 PG 5 WC Hematology SC Hematology GA GM787 UT WOS:A1991GM78700038 PM 1932755 ER PT J AU CAPLAN, LJ BARR, RA AF CAPLAN, LJ BARR, RA TI THE EFFECTS OF FEATURE NECESSITY AND EXTRINSICITY ON GRADEDNESS OF CATEGORY MEMBERSHIP AND CLASS INCLUSION RELATIONS SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Article ID REPRESENTATIONS C1 NIA,BETHESDA,MD 20892. RP CAPLAN, LJ (reprint author), NIMH,SOCIOENVIRONM STUDIES LAB,FED BLDG ROOM B1A-14,BETHESDA,MD 20892, USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48, PRINCESS RD, EAST, LEICESTER, LEICS, ENGLAND LE1 7DR SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD NOV PY 1991 VL 82 BP 427 EP 440 PN 4 PG 14 WC Psychology, Multidisciplinary SC Psychology GA GR963 UT WOS:A1991GR96300002 ER PT J AU BALDWIN, W AF BALDWIN, W TI PERSPECTIVES IN RESEARCH ON ADOLESCENCE SO BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT CONF ON STRENGTH AND POTENTIALS OF ADOLESCENCE CY MAR 18, 1991 CL NEW YORK, NY SP NEW YORK ACAD MED, COMM PUBLIC HLTH C1 NICHHD,CTR POPULAT RES,DEMOG & BEHAV SCI BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD MEDICINE PI NEW YORK PA 1216 FIFTH AVE, NEW YORK, NY 10029 SN 0028-7091 J9 B NEW YORK ACAD MED JI Bull. N. Y. Acad. med. PD NOV-DEC PY 1991 VL 67 IS 6 BP 548 EP 554 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA GX184 UT WOS:A1991GX18400004 PM 1802327 ER PT J AU IIJIMA, S INGRAM, DK SPANGLER, EL HELLER, B GAROFALO, P AF IIJIMA, S INGRAM, DK SPANGLER, EL HELLER, B GAROFALO, P TI HEPTOPHYSOSTIGMINE ATTENUATES THE EFFECTS OF SCOPOLAMINE IN A 14-UNIT T-MAZE SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1991 VL 29 IS 6 BP 486 EP 487 PG 2 WC Psychology, Mathematical SC Psychology GA GL115 UT WOS:A1991GL11500156 ER PT J AU SALO, AL SHAPIRO, LE DEWSBURY, DA AF SALO, AL SHAPIRO, LE DEWSBURY, DA TI DIFFERENCES IN AFFILIATIVE BEHAVIOR AMONG VOLES (MICROTUS) SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 UNIV FLORIDA,GAINESVILLE,FL 32611. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1991 VL 29 IS 6 BP 487 EP 487 PG 1 WC Psychology, Mathematical SC Psychology GA GL115 UT WOS:A1991GL11500159 ER PT J AU INGRAM, DK HENGEMIHLE, JM LONG, J GAROFALO, P AF INGRAM, DK HENGEMIHLE, JM LONG, J GAROFALO, P TI STANDARDIZING A PSYCHOMOTOR TEST BATTERY FOR ASSESSING AGING IN MICE SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1991 VL 29 IS 6 BP 498 EP 498 PG 1 WC Psychology, Mathematical SC Psychology GA GL115 UT WOS:A1991GL11500290 ER PT J AU CAPLAN, LJ SCHOOLER, C AF CAPLAN, LJ SCHOOLER, C TI ANALOGIES, SIMILARITIES, AND ABSTRACTION SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1991 VL 29 IS 6 BP 507 EP 507 PG 1 WC Psychology, Mathematical SC Psychology GA GL115 UT WOS:A1991GL11500383 ER PT J AU GIAMBRA, L WEINGARTNER, H ARENBERG, D COSTA, P ZONDERMAN, A FRIZ, J METTER, E KAWAS, C AF GIAMBRA, L WEINGARTNER, H ARENBERG, D COSTA, P ZONDERMAN, A FRIZ, J METTER, E KAWAS, C TI AGE MEMORY CHANGES A NECESSARY CONSEQUENCE OF AGING SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1991 VL 29 IS 6 BP 508 EP 508 PG 1 WC Psychology, Mathematical SC Psychology GA GL115 UT WOS:A1991GL11500391 ER PT J AU LINET, MS MCLAUGHLIN, JK HSING, AW WACHOLDER, S COCHIEN, HT SCHUMAN, LM BJELKE, E BLOT, WJ AF LINET, MS MCLAUGHLIN, JK HSING, AW WACHOLDER, S COCHIEN, HT SCHUMAN, LM BJELKE, E BLOT, WJ TI CIGARETTE-SMOKING AND LEUKEMIA - RESULTS FROM THE LUTHERAN BROTHERHOOD COHORT STUDY SO CANCER CAUSES & CONTROL LA English DT Article DE CIGARETTE SMOKING; LEUKEMIA; PROSPECTIVE STUDY; UNITED-STATES AB In a 20-year follow-up (1966-86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR] = 2.7), and other and unspecified leukemia (RR = 1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking. RP LINET, MS (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA,N ROOM 415B,BETHESDA,MD 20892, USA. NR 0 TC 21 Z9 22 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1991 VL 2 IS 6 BP 413 EP 417 DI 10.1007/BF00054302 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA GW591 UT WOS:A1991GW59100007 PM 1764566 ER PT J AU CHOW, WH DEVESA, SS BLOT, WJ AF CHOW, WH DEVESA, SS BLOT, WJ TI COLON CANCER INCIDENCE - RECENT TRENDS IN THE UNITED-STATES SO CANCER CAUSES & CONTROL LA English DT Article DE COLON CANCER; INCIDENCE; RACE; STAGE; UNITED-STATES AB Between 1976-78 and 1985-87, the age-adjusted incidence rates of invasive colon cancer in the United States rose by 15 percent, 3 percent, 21 percent, and 16 percent among White males, White females, Black males, and Black females, respectively. The increases in incidence occurred in all age groups over age 54 and affected each of the major subsites of the colon nearly equally. The larger rates of increase have resulted in higher incidence among Blacks than Whites by the mid-1980s and an increasingly greater excess of this cancer in males. Trends toward earlier diagnosis of invasive colon cancer were found, with increasing rates for localized and regional diseases coupled with stable or decreasing distant-stage disease-rates. The incidence of in situ colon cancer also rose substantially. The findings suggest that changes in diagnostic trends and risk-factor prevalence may be contributing to these patterns, and that the era when colon cancer predominated among White females is clearly over. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EPN ROOM 407,ROCKVILLE,MD 20892, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1991 VL 2 IS 6 BP 419 EP 425 DI 10.1007/BF00054303 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA GW591 UT WOS:A1991GW59100008 PM 1764567 ER PT J AU LINK, CJ BURT, RK BOHR, VA AF LINK, CJ BURT, RK BOHR, VA TI GENE-SPECIFIC REPAIR OF DNA DAMAGE INDUCED BY UV IRRADIATION AND CANCER CHEMOTHERAPEUTICS SO CANCER CELLS-A MONTHLY REVIEW LA English DT Review ID HAMSTER OVARY CELLS; TRANSCRIPTIONALLY ACTIVE DNA; DIHYDROFOLATE-REDUCTASE GENE; COMPLEMENTATION GROUP-C; CROSS-LINKS; DIFFERENTIAL REPAIR; MITOCHONDRIAL-DNA; ESCHERICHIA-COLI; EXCISION REPAIR; DHFR GENE AB DNA repair processes are critically important in the prevention of carcinogenesis, and currently much research is directed toward elucidation of the biochemical mechanisms by which DNA repair occurs. Techniques have been developed for examining individual genes to quantitate the lesions induced by various chemotherapeutic agents and to measure the rate of gene-specific DNA repair. In mammalian cells, the DNA repair response exhibits intragenomic heterogeneity-active genes are preferentially repaired and the transcribed strand of DNA is repaired more rapidly than the nontranscribed strand. These studies have provided new insight into the molecular biology of DNA repair and a new perspective on the role of repair processes in cellular resistance to DNA damage and malignancy. Elucidation of the mechanisms by which gene-specific lesions are formed and repaired will be important if we are to understand the fundamental processes of malignancy. C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP LINK, CJ (reprint author), NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 21 Z9 21 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD NOV PY 1991 VL 3 IS 11 BP 427 EP 436 PG 10 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA GR445 UT WOS:A1991GR44500003 PM 1760244 ER PT J AU NETA, R OPPENHEIM, JJ AF NETA, R OPPENHEIM, JJ TI RADIOPROTECTION WITH CYTOKINES - A CLARIFICATION OF TERMINOLOGY SO CANCER CELLS-A MONTHLY REVIEW LA English DT Letter C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP NETA, R (reprint author), ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814, USA. NR 3 TC 1 Z9 2 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD NOV PY 1991 VL 3 IS 11 BP 457 EP 457 PG 1 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA GR445 UT WOS:A1991GR44500007 PM 1760247 ER PT J AU DEVESA, SS SHAW, GL BLOT, WJ AF DEVESA, SS SHAW, GL BLOT, WJ TI CHANGING PATTERNS OF LUNG-CANCER INCIDENCE BY HISTOLOGICAL TYPE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; CIGARETTE-SMOKING; INCIDENCE RATES; CELL TYPE; CARCINOMA; TRENDS; WOMEN; RISK; HISTOPATHOLOGY; DIAGNOSIS AB Using data from five registries covering 7% of the U.S. population, we investigated lung carcinoma incidence trends from 1969-86 by histological type, sex, race, age, calendar time period, and cohort year of birth. Among white men, squamous cell carcinoma was the most frequent histological type, but by the mid-1980s the age-adjusted rates were decreasing while rates of adenocarcinoma and small (oat) cell carcinoma continued to rise. Among white women, adenocarcinoma was the most frequent type, followed by small cell carcinoma, with rates of all histological types rising over the entire study period. Similar time trends were seen among blacks. Rates for squamous cell carcinoma among both sexes and adenocarcinoma among men, however, were considerably higher for blacks than whites, whereas no racial disparity was seen for small cell carcinomas. Rates for each histological type were higher among men than women, although male-female sex ratios diminished over time. Age-specific rates varied considerably by cohort year of birth; incidence of squamous cell carcinoma among men increased steadily among those born from the late 1800s to the first quarter of this century before declining among those born thereafter. Cohort peaks were also reached, although about 10 to 20 years later, for small cell carcinoma and adenocarcinoma, suggesting an eventual reduction in incidence in these histological types as well. For each type, the peak incidence occurred earlier for men than women. These differing incidence patterns add to the evidence that the mechanisms of lung carcinogenesis may vary by histological type. RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 39 TC 128 Z9 129 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1991 VL 1 IS 1 BP 29 EP 34 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HN950 UT WOS:A1991HN95000006 PM 1845165 ER PT J AU PALLI, D DECARLI, A CIPRIANI, F FORMAN, D AMADORI, D AVELLINI, C GIACOSA, A MANCA, P RUSSO, A SALKELD, RM SAMLOFF, IM FRAUMENI, JF BLOT, WJ BUIATTI, E AF PALLI, D DECARLI, A CIPRIANI, F FORMAN, D AMADORI, D AVELLINI, C GIACOSA, A MANCA, P RUSSO, A SALKELD, RM SAMLOFF, IM FRAUMENI, JF BLOT, WJ BUIATTI, E TI PLASMA PEPSINOGENS, NUTRIENTS, AND DIET IN AREAS OF ITALY AT VARYING GASTRIC-CANCER RISK SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC ATROPHIC GASTRITIS; MICRONUTRIENT LEVELS; STOMACH-CANCER; POPULATION AB In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy at different risks for gastric cancer (GC), plasma levels of pepsinogens (PGI and PGII) and fat-soluble vitamins were assayed. Pepsinogen levels were used to identify individuals with chronic atrophic gastritis (CAG). Severe CAG (PGI less-than-or-equal-to 20 pg/liter) affected 5.8% of the population, but the prevalence rose with increasing age and declining social class. Severe CAG was 5 times more common in areas with high compared to low rates of GC. Risk also rose with increasing consumption of salted/dried fish but was inversely related to dietary intake of beta-carotene and to plasma retinol and cholesterol levels. The prevalence of moderate CAG (PGI > 20 pg/liter, but PGI/PGII less-than-or-equal-to 2.9) was 6.3%. Moderate CAG was also related to age and social class and increased 1.8-fold in areas where GC rates were high, but was not strongly associated with diet or plasma nutrients. The authors discuss these findings in relation to those from a previous case-control study of GC in the same areas. C1 UNIV MILAN,IST STAT MED & BIOMETRIA,I-20122 MILAN,ITALY. IST NAZL TUMORI,I-20133 MILAN,ITALY. IMPERIAL CANC RES FUND,CANC EPIDEMIOL UNIT,OXFORD,ENGLAND. OSPED MORGAGNI PIERANTONI,SERV ONCOL,FORLI,ITALY. OSPED IMOLA,SERV ANAT PATOL,IMOLA,ITALY. IST NAZL RIC CANC,GENOA,ITALY. UNIV CAGLIARI,IST MED LAVORO,I-09100 CAGLIARI,ITALY. F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND. VET ADM MED CTR,SEPULVEDA,CA 91343. NCI,BETHESDA,MD 20892. RP PALLI, D (reprint author), CTR STUDIO & PREVENZ ONCOL,EPIDEMIOL UNIT,VIALE VOLTA 171,I-50131 FLORENCE,ITALY. RI Decarli, Adriano/C-3129-2017; OI Decarli, Adriano/0000-0003-1451-8292; PALLI, Domenico/0000-0002-5558-2437 FU NCI NIH HHS [N01-CP-51019] NR 31 TC 29 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1991 VL 1 IS 1 BP 45 EP 50 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HN950 UT WOS:A1991HN95000008 PM 1845168 ER PT J AU TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N UNRUH, L KADLUBAR, FF BARTSCH, H MALAVEILLE, C VINEIS, P AF TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N UNRUH, L KADLUBAR, FF BARTSCH, H MALAVEILLE, C VINEIS, P TI DETECTION OF CARCINOGEN-DNA ADDUCTS IN EXFOLIATED UROTHELIAL CELLS OF CIGARETTE SMOKERS - ASSOCIATION WITH SMOKING, HEMOGLOBIN ADDUCTS, AND URINARY MUTAGENICITY SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BLADDER-CANCER; P-32-POSTLABELING ASSAY; AROMATIC-AMINES; TOBACCO; TISSUES; NONSMOKERS; DOSIMETRY; PHENOTYPE; EXPOSURE; INVIVO AB The presence of covalent modifications in DNA obtained from exfoliated urothelial cells of smokers and nonsmokers was determined using P-32 postlabeling methods. Urine and blood samples were procured from 73 persons. Cells were removed from the urine by filtration. DNA was isolated using an enzyme-solvent extraction method and then coprecipitated with glycogen. Sufficient DNA to detect 1 carcinogen-DNA adduct/10(9) normal nucleotides was obtained from 40 of the 73 samples. DNA was hydrolyzed to 3'phosphodeoxynucleotides and then P-32 postlabeled under conditions of excess [P-32]ATP. Carcinogen-DNA adducts were resolved using anion-exchange thin-layer chromatography and visualized by autoradiography; film exposures lasted as long as 7 days. Twelve different carcinogen-DNA adducts and a diagonal zone of radioactivity could be found, but no sample contained all adducts. At least four adducts appeared to be cigarette smoking related. These adducts were from 2 to 20 times higher in the smokers than the nonsmokers. Two carcinogen-DNA adducts were qualitatively very similar to adducts described earlier in a study of human bladder biopsies. One of these corresponded to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. Adducts were correlated significantly with the levels of 4-aminobiphenyl hemoglobin adducts and number of cigarettes smoked. In addition, levels of the putative N-(deoxyguanosin-8-yl)-4-aminobiphenyl adduct and a measure of total adducts were correlated with the mutagenic activity of the individual's urine. These data suggest that noninvasive, biological monitoring techniques can be applied to the study of carcinogen-DNA adducts in humans at high risk for bladder cancer. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. MIT,DIV TOXICOL,CAMBRIDGE,MA 02139. NCI,FAMILY STUDIES SECT,BETHESDA,MD 20892. NATL CTR TOXICOL RES,OFF RES,JEFFERSON,AR 72079. INT AGCY RES CANC,F-69372 LYONS,FRANCE. DIPARTIMENTO SCI BIOMED & ONCOL UMANA,CANC EPIDEMIOL UNIT,TURIN,ITALY. RP TALASKA, G (reprint author), UNIV CINCINNATI,INST ENVIRONM HLTH,CINCINNATI,OH 45267, USA. FU NIEHS NIH HHS [ES 00597] NR 34 TC 124 Z9 127 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 NOV-DEC PY 1991 VL 1 IS 1 BP 61 EP 66 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HN950 UT WOS:A1991HN95000011 PM 1845172 ER PT J AU LI, FP CORREA, P FRAUMENI, JF AF LI, FP CORREA, P FRAUMENI, JF TI TESTING FOR GERM LINE P53 MUTATIONS IN CANCER FAMILIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. NR 6 TC 28 Z9 28 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 NOV-DEC PY 1991 VL 1 IS 1 BP 91 EP 94 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HN950 UT WOS:A1991HN95000015 PM 1845175 ER PT J AU PRICE, FM PARSHAD, R TARONE, RE SANFORD, KK AF PRICE, FM PARSHAD, R TARONE, RE SANFORD, KK TI RADIATION-INDUCED CHROMATID ABERRATIONS IN COCKAYNE SYNDROME AND XERODERMA-PIGMENTOSUM GROUP-C FIBROBLASTS IN RELATION TO CANCER PREDISPOSITION SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TRANSCRIPTIONALLY ACTIVE DNA; ATAXIA TELANGIECTASIA; CELL-CYCLE; CHROMOSOMAL RADIOSENSITIVITY; ULTRAVIOLET-LIGHT; FLUORESCENT LIGHT; G2 PHASE; REPAIR; DAMAGE; SUSCEPTIBILITY AB We showed previously that the persistence of chromatid breaks and gaps after G, phase irradiation with X-rays or near-UV visible light characterizes skin fibroblasts from individuals with cancer-prone genetic diseases. This abnormal response appears to result from deficient DNA repair during G2 and to be associated with cancer proneness. We have, therefore, compared the responses of cells from two genetic disorders, Cockayne syndrome (CS) and xeroderma pigmentosum complementation group C (XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either X-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. This deficient repair in the presence of DNA damage and continuous cell cycling from activation of proto-oncogenes or loss of suppressor genes may be necessary and sufficient for cancer development. C1 NCI,CELLULAR & MOLEC BIOL LAB,ROOM 2D15,BLDG 37,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20001. NR 48 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE 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 NOV PY 1991 VL 57 IS 1 BP 1 EP 10 DI 10.1016/0165-4608(91)90183-U PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GZ020 UT WOS:A1991GZ02000001 PM 1756475 ER PT J AU KATSANIS, E BAUSERO, MA OCHOA, AC LOEFFLER, CM BLAZAR, BR LEONARD, AS ANDERSON, PM AF KATSANIS, E BAUSERO, MA OCHOA, AC LOEFFLER, CM BLAZAR, BR LEONARD, AS ANDERSON, PM TI IMPORTANCE IN TIMING OF CYCLOPHOSPHAMIDE ON THE ENHANCEMENT OF INTERLEUKIN-2-INDUCED CYTOLYSIS SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CYCLOPHOSPHAMIDE; IL-2, NK ACTIVITY; CYTOLYSIS ID NATURAL-KILLER CELLS; CHEMO-IMMUNOTHERAPY; RECOMBINANT INTERLEUKIN-2; MURINE TUMOR; T-CELLS; MICE; MELANOMA; LYMPHOCYTES; REGRESSION; INDUCTION AB We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL-2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days -10 and -15 followed by IL-2 (50 000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day -10 or -15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoG(M1), prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration. C1 UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. NCI,PROGRAM RESOURCES INC,FREDERICK,MD 21701. RP KATSANIS, E (reprint author), UNIV MINNESOTA,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,BOX 484 UMHC,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [R01-CA-21 737]; NIAID NIH HHS [N01-AI-85 002] NR 24 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 1991 VL 34 IS 2 BP 74 EP 78 DI 10.1007/BF01741339 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA GQ471 UT WOS:A1991GQ47100002 PM 1760819 ER PT J AU LIJINSKY, W AF LIJINSKY, W TI THE ANOMALOUS BIOLOGICAL-ACTIVITY OF NITROSO-2-OXOPROPYL COMPOUNDS SO CANCER LETTERS LA English DT Article DE NITROSO-OXOPROPYLAMINES; NITROSOUREAS; ALKYLATION; RATS; HAMSTERS; TUMORS ID NUCLEIC-ACID ALKYLATION; SYRIAN-HAMSTERS; F344 RATS; CARCINOGENESIS; N-NITROSOBIS(2-OXOPROPYL)AMINE; DNA; N-NITROSOMETHYL(2-OXOPROPYL)AMINE; N-NITROSO-2,6-DIMETHYLMORPHOLINE; NITROSOBIS-(2-OXOPROPYL)AMINE; NITROSAMINES AB The carcinogenic action of a set of N-nitroso compounds containing the 2-oxopropyl group was considered in relation to their metabolism and their activity as alkylating agents for DNA. In contrast with the great carcinogenic potency of methylnitrosourea and ethylnitrosourea, comparable with the corresponding dialkylnitrosamines, 2-oxopropylnitrosourea is a weak carcinogen with a limited range of target organs in rats and hamsters. 2-Oxopropylnitrosochloroethylurea was somewhat weaker than 2-oxopropylnitrosourea and similarly induced spleen hemangiosarcomas in hamsters, but few tumors of any kind in rats. The relatively much more potent carcinogenicity of nitrosobis-(2-oxopropyl)amine, nitroso-(2-hydroxypropyl)(2-oxopropyl)amine and methyl-nitroso-2-oxopropylamine suggests that the activity of an oxopropylating agent is not involved in carcinogenesis by nitroso-2-oxopropylamines. The nitrosamines are likely to undergo extensive metabolism to form proximate carcinogenic moieties, probably including the methyldiazonium ion, which are responsible for the induction of a broad range of tumors in rats and hamsters. These include tumors of the liver, pancreas ducts, lung and nasal mucosa in hamsters, and esophagus, liver, lung, thyroid, kidney, trachea, bladder and nasal mucosa in rats. C1 NCI,CTR CANC RES & DEV,CHEM & PHYS CARCINOGENESIS LAB,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74101] NR 21 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV PY 1991 VL 60 IS 2 BP 121 EP 127 DI 10.1016/0304-3835(91)90218-7 PG 7 WC Oncology SC Oncology GA GL936 UT WOS:A1991GL93600005 PM 1933836 ER PT J AU ALEXANDROV, VA BESPALOV, VG BOONE, CW KELLOFF, GJ MALONE, WF AF ALEXANDROV, VA BESPALOV, VG BOONE, CW KELLOFF, GJ MALONE, WF TI STUDY OF POSTNATAL EFFECTS OF CHEMOPREVENTIVE AGENTS ON OFFSPRING OF ETHYLNITROSOUREA-INDUCED TRANSPLACENTAL CARCINOGENESIS IN RATS .1. INFLUENCE OF RETINOL ACETATE, ALPHA-TOCOPHEROL ACETATE, THIAMINE CHLORIDE, SODIUM SELENITE, AND ALPHA-DIFLUOROMETHYLORNITHINE SO CANCER LETTERS LA English DT Article DE TRANSPLACENTAL CARCINOGENESIS; RATS; VITAMINS; SODIUM SELENITE; ALPHA-DIFLUOROMETHYLORNITHINE ID TUMORS; INHIBITION; CANCER; MICE; PREVENTION AB We studied the influence of the vitamins retinol acetate, alpha-tocopherol acetate and thiamine chloride; the antioxidant sodium selenite and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine, on the offspring of transplacental carcinogenesis by ethylnitrosourea in rats. Ethylnitrosourea was given to pregnant rats as a single i.v. injection, at a dose of 75 mg/kg body wt. or 5.5 mg/kg body wt., on the 21st day after conception. Retinol, tocopherol or thiamine was added to the diet, and selenite and alpha-difluoromethylornithine to drinking water of the offspring throughout their postnatal life at moderate doses. In control groups, ethylnitrosourea induced tumors of brain, spinal cord, peripheral nervous system and kidneys in the offspring. alpha-Difluoromethylornithine exerted a slight inhibitory effect; this agent decreased the total tumor multiplicity and the multiplicity of peripheral nervous system tumors and also prolonged survival time. Retinol, tocopherol, thiamine and selenite did not influence the development of the transplacentally-induced tumors. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. PETROV ONCOL RES INST,PRECLIN TRIALS LAB,LENINGRAD 189646,USSR. NR 33 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV PY 1991 VL 60 IS 2 BP 177 EP 184 DI 10.1016/0304-3835(91)90225-7 PG 8 WC Oncology SC Oncology GA GL936 UT WOS:A1991GL93600012 PM 1657370 ER PT J AU NACKERDIEN, Z KASPRZAK, KS RAO, G HALLIWELL, B DIZDAROGLU, M AF NACKERDIEN, Z KASPRZAK, KS RAO, G HALLIWELL, B DIZDAROGLU, M TI NICKEL(II)-DEPENDENT AND COBALT(II)-DEPENDENT DAMAGE BY HYDROGEN-PEROXIDE TO THE DNA BASES IN ISOLATED HUMAN CHROMATIN SO CANCER RESEARCH LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; CARCINOGENIC NICKEL COMPOUNDS; RADICAL FORMATION; DEOXYRIBONUCLEIC-ACID; PROTEIN CROSSLINKS; COBALT; HYDROXYL; SUPEROXIDE; OXIDATION; METAL AB Nickel compounds are known to be carcinogenic to humans and animals. Cobalt compounds produce tumors in animals and are probably carcinogenic to humans. The mechanisms of the carcinogenicity of these metal compounds, however, have remained elusive. In the present work, we have investigated the ability of Ni(II) and Co(II) ions in the presence of H2O2 to cause chemical changes in DNA bases in chromatin extracted from cultured cells of human origin. Eleven modified DNA bases in chromatin were identified and quantitated by the use of gas chromatography-mass spectrometry. 2-Hydroxyadenine (isoguanine), which has not previously been shown to occur in DNA or chromatin, was also identified. Products identified were typical hydroxyl radical-induced products of DNA bases, suggesting that the hydroxyl radical was involved in their formation. This idea was supported by partial inhibition of product formation by typical scavengers of hydroxyl radical. Partial inhibition of product formation indicated a possible "site-specific" formation of hydroxyl radical by unchelated Ni(II) and Co(II) ions bound to chromatin. Although treatment of chromatin for 1 h with Co(II)/H2O2 caused formation of significant amounts of products, treatment with Ni(Il)/H2O2 required incubation times of more than 5 h and an increase in Ni(II) concentration before increases in product amounts above background levels became detectable. In both cases, ascorbic acid did not increase product yields. Glutathione at a physiologically relevant concentration had little overall effect on DNA base modification. Superoxide dismutase increased the yields of most products. Chelation of Ni(II) and Co(II) ions with EDTA almost completely inhibited product formation. Ni(II) in the presence of H2O2 produced greater base damage to the DNA in chromatin than to isolated DNA, unlike other metal ions tested. DNA damage in chromatin caused by Ni(II) and Co(II) ions in the presence Of H2O2 May contribute to the established genotoxicity and carcinogenicity of these metal ions. C1 NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899. UNIV STELLENBOSCH,DEPT RADIOTHERAPY,TYGERBERG 7505,SOUTH AFRICA. UNIV MARYLAND,BALTIMORE,MD 21201. MARYLAND BIOTECHNOL INST,CTR MED BIOTECHNOL,BALTIMORE,MD 21228. NCI,FREDERICK CANC RES DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CALIF DAVIS,SACRAMENTO MED CTR,SACRAMENTO,CA 95817. RI Halliwell, Barry/C-8318-2009 NR 57 TC 115 Z9 116 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 NOV 1 PY 1991 VL 51 IS 21 BP 5837 EP 5842 PG 6 WC Oncology SC Oncology GA GM477 UT WOS:A1991GM47700010 PM 1933852 ER PT J AU HUGGETT, AC ELLIS, PA FORD, CP HAMPTON, LL RIMOLDI, D THORGEIRSSON, SS AF HUGGETT, AC ELLIS, PA FORD, CP HAMPTON, LL RIMOLDI, D THORGEIRSSON, SS TI DEVELOPMENT OF RESISTANCE TO THE GROWTH INHIBITORY EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA-1 DURING THE SPONTANEOUS TRANSFORMATION OF RAT-LIVER EPITHELIAL-CELLS SO CANCER RESEARCH LA English DT Article ID CHOLINE-DEVOID DIET; METHYL-DEFICIENT DIETS; MESSENGER-RNA; FACTOR-BETA; HEPATOCELLULAR-CARCINOMA; V-RAF; NEOPLASTIC TRANSFORMATION; TUMOR PROGRESSION; FACTOR-ALPHA; TGF-BETA AB The temporary maintenance of a rat liver epithelial cell population at confluence before passaging followed by periods of rapid proliferation resulted in the generation of spontaneous transformants after about 108 population doublings. The appearance of morphologically aberrant transformants correlated directly with an increased resistance of the population to the growth inhibitory effects of transforming growth factor-beta-1 (TGF-beta-1). Clonal cell lines derived from the transformants were resistant to TGF-beta-1 dependent inhibition of DNA synthesis. These cell lines were also highly tumorigenic and aneuploid, with characteristic gross chromosomal abnormalities, and they expressed a number of phenotypic markers common to rat liver epithelial cells transformed by oncogenes or chemicals. In contrast, apparently normal looking cell lines cloned from the same population were nontumorigenic and near diploid, with few chromosomal abnormalities, and they were as sensitive to TGF-beta-1 as early passage normal rat liver epithelial cells. Morphologically normal late passage rat liver epithelial cells were sensitive to transformation by the DNA hypomethylating agent 5-aza-2-deoxycytidine, in contrast to earlier passage cells, and this transformation was accompanied by the development of resistance to the growth inhibitory effects of TGF-beta-1. These findings suggest that acquisition of resistance to the effects of growth inhibitors such as TGF-beta-1 is an important and possibly essential stage in the spontaneous transformation of rat liver epithelial cells. C1 NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NR 61 TC 61 Z9 62 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 NOV 1 PY 1991 VL 51 IS 21 BP 5929 EP 5936 PG 8 WC Oncology SC Oncology GA GM477 UT WOS:A1991GM47700024 PM 1718589 ER PT J AU SHEIBANI, N RHIM, JS ALLENHOFFMANN, BL AF SHEIBANI, N RHIM, JS ALLENHOFFMANN, BL TI MALIGNANT HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED HUMAN KERATINOCYTES EXHIBIT ALTERED EXPRESSION OF EXTRACELLULAR-MATRIX GLYCOPROTEINS SO CANCER RESEARCH LA English DT Article ID GROWTH FACTOR-BETA; HUMAN EPIDERMAL-KERATINOCYTES; HUMAN FORESKIN KERATINOCYTES; CULTURED HUMAN KERATINOCYTES; TRACHEAL EPITHELIAL-CELLS; NEOPLASTIC TRANSFORMATION; MESSENGER-RNA; TERMINAL DIFFERENTIATION; HUMAN-FIBROBLASTS; CERVICAL-CARCINOMA AB We found that keratinocytes immortalized with human papillomavirus (HPV) type 16 DNA and malignantly converted by H-ras transfection (HPK-1A/ras) exhibit an enhanced ability to synthesize a fibronectin-containing extracellular matrix. Gene expression of fibronectin and thrombospondin was increased in tumorigenic keratinocytes compared to control and immortalized keratinocytes, 6- and 9-fold, respectively. Increased production of soluble and cell surface-associated fibronectin was not specific for HPV 16 transformed keratinocytes. Ad12-SV40-immortalized keratinocytes malignantly converted by H-ras transfection (RHEK-1/ras) also exhibited enhanced expression of fibronectin and thrombospondin, as well as pro-alpha-1 type I collagen. Steady state mRNA levels for autocrine growth-regulatory factors, transforming growth factors-alpha and-beta-1, were increased in Ad12-SV40 but not HPV 16-transformed human keratinocytes. We then determined whether increased production of fibronectin was associated with aberrant differentiation of transformed keratinocytes. Less than 10% of the HPV 16-transformed cells produced cornified envelopes after suspension-induced differentiation compared to 70% of normal keratinocytes. However, immortalization by HPV 16 DNA was sufficient to confer a differentiation-defective phenotype. Both involucrin mRNA and protein levels were decreased 8-fold in HPV 16-immortalized keratinocytes compared to normal cells and malignant conversion further attenuated involucrin levels. These studies demonstrate that aberrant differentiation is an early event in the transformation of the human keratinocytes and is not the result of enhanced expression of the extracellular matrix proteins. Unlike transformed fibroblastic cell types, up-regulation of fibronectin gene expression and matrix formation is a consistent characteristic of malignantly converted human keratinocytes. C1 UNIV WISCONSIN,DEPT PATHOL,MADISON,WI 53706. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [R29 AR40284]; NICHD NIH HHS [HD07118] NR 67 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1991 VL 51 IS 21 BP 5967 EP 5975 PG 9 WC Oncology SC Oncology GA GM477 UT WOS:A1991GM47700030 PM 1657375 ER PT J AU RICHTER, KH AFSHARI, CA ANNAB, LA BURKHART, BA OWEN, RD BOYD, J BARRETT, JC AF RICHTER, KH AFSHARI, CA ANNAB, LA BURKHART, BA OWEN, RD BOYD, J BARRETT, JC TI DOWN-REGULATION OF CDC2 IN SENESCENT HUMAN AND HAMSTER-CELLS SO CANCER RESEARCH LA English DT Note ID CYCLE CONTROL; HUMAN-FIBROBLASTS; KINASE; GENE; PHOSPHORYLATION; EXPRESSION; ACTIVATION; PRODUCT; PROTEIN AB Senescent cells fail to respond to serum-induced signals for DNA synthesis. Because a central role for the p34cdc2 protein kinase is postulated in control of the cell cycle, we examined the status of this kinase in senescent cells and other growth-arrested cells. In growing human and Syrian hamster fibroblasts, three S-35-labeled proteins of 34-36 kDa were immunoprecipitated with p34cdc2 antiserum. Only the two slower migrating forms were phosphorylated as determined by P-32-labeling. In senescent cells, which failed to incorporate [H-3]thymidine, no p34cdc2 protein was synthesized and very little or no cdc2 mRNA was observed. When maintained for 48 h in 0.5% serum, young cells also retained only marginal cdc2 expression. After stimulation of low serum-arrested cells by addition of 10% serum, a time-dependent increase of cdc2 mRNA was observed, whereas serum stimulation of senescent cells did not increase cdc2 mRNA. In contrast to senescent and low serum-arrested cells, cdc2 mRNA was expressed at normal levels in cells partially growth arrested by isoleucine deficiency in G1, by aphidicolin at G1-S, by etoposide in G2, or by Colcemid in the M phase of the cell cycle, indicating that cdc2 down-regulation does not always occur upon growth arrest. Following transfection of a plasmid containing the human CDC2 gene into hamster cells, expression of human cdc2 failed to overcome the block to DNA synthesis in senescent cells. Although p34cdc2 was synthesized in the transfected cells, the multiple phosphorylated forms of the protein were not observed. Taken together, these data support the concept that a chain of events leads to senescence. While p34cdc2 kinase may be one of the critical elements, other cell cycle controls are also involved. C1 NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 20 TC 58 Z9 59 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1991 VL 51 IS 21 BP 6010 EP 6013 PG 4 WC Oncology SC Oncology GA GM477 UT WOS:A1991GM47700038 PM 1933864 ER PT J AU BOHR, VA AF BOHR, VA TI GENE SPECIFIC DNA-REPAIR SO CARCINOGENESIS LA English DT Note ID HAMSTER OVARY CELLS; DIHYDROFOLATE-REDUCTASE GENE; COMPLEMENTATION GROUP-C; EXCISION REPAIR; MAMMALIAN-CELLS; DIFFERENTIAL REPAIR; STRAND SPECIFICITY; PYRIMIDINE DIMERS; MITOCHONDRIAL-DNA; ESCHERICHIA-COLI RP BOHR, VA (reprint author), NCI,MOLEC PHARMACOL LAB,BLDG 37 RM 5C-25,BETHESDA,MD 20892, USA. NR 68 TC 180 Z9 181 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1991 VL 12 IS 11 BP 1983 EP 1992 DI 10.1093/carcin/12.11.1983 PG 10 WC Oncology SC Oncology GA GP558 UT WOS:A1991GP55800001 PM 1934282 ER PT J AU HUITFELDT, HS HEYDEN, A CLAUSEN, OPF THRANE, EV ROOP, D YUSPA, SH AF HUITFELDT, HS HEYDEN, A CLAUSEN, OPF THRANE, EV ROOP, D YUSPA, SH TI ALTERED REGULATION OF GROWTH AND EXPRESSION OF DIFFERENTIATION-ASSOCIATED KERATINS IN BENIGN MOUSE SKIN TUMORS SO CARCINOGENESIS LA English DT Article ID GENE-EXPRESSION; EPIDERMIS; CARCINOGENESIS; CELLS; PAPILLOMAS; KINETICS; COMPARTMENT; ANTIBODIES; THYMIDINE; PEPTIDES AB Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromodeoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K10. In normal mouse skin, pulse-chase experiments for 120 h revealed that replication was restricted to a single layer of basal cells. Replicating cells did not express K1 or K10, but these keratins were sequentially expressed in post-mitotic basal cells 18 and 24 h following DNA synthesis respectively, and cells expressing these keratins migrated into the suprabasal layers. In phorbol-ester- or cantharidin-stimulated hyperplastic skin, replicating cells were also confined to the basal cell compartment and suprabasal cells expressed keratins 1 and 10. In papillomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate, replication occurred predominantly in cells in an expanded basal cell compartment (two to four layers above the basement membrane). Cells in these basal layers did not express K1 or K10, but more superficial cells did. After a 1 h pulse of BrdU, replication was also identified in suprabasal cells expressing the differentiation-associated keratins. These and other results suggest that benign tumor cells escape the obligatory growth arrest associated with differentiation. Replication of K1- and K10-expressing suprabasal cells may represent an early alteration during mouse skin carcinogenesis. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UNIV OSLO,RIKSHOSP,INST PATHOL,OSLO,NORWAY. NR 27 TC 56 Z9 56 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1991 VL 12 IS 11 BP 2063 EP 2067 DI 10.1093/carcin/12.11.2063 PG 5 WC Oncology SC Oncology GA GP558 UT WOS:A1991GP55800013 PM 1718620 ER PT J AU SHOUKRY, S ANDERSON, MW GLICKMAN, BW AF SHOUKRY, S ANDERSON, MW GLICKMAN, BW TI A NEW TECHNIQUE FOR DETERMINING THE DISTRIBUTION OF N7-METHYLGUANINE USING AN AUTOMATED DNA SEQUENCER SO CARCINOGENESIS LA English DT Article ID LACI GENE; SITES; POLYMERASE; CLEAVAGE; CLONING AB We have developed a method to determine rapidly the sequence specificity of DNA alkylation resulting from chemical treatment. The utility of this approach is demonstrated here in a study of the sequence specificity of alkylation by dimethylsulphate (DMS). The method is independent of the sequence chosen and makes use of the polymerase chain reaction (PCR) to generate a fluorescently labelled DNA target. In this study, a 302 bp segment of the Escherichia coli lacI gene was amplified and the product purified by liquid chromatography on a Mono Q column. This DNA was alkylated with DMS and treated with hot piperidine to produce single-strand breaks at sites of N7 alkylation. The distribution of the break points, and hence the position and extent of alkylation, were determined on an Applied Biosystems 370A automated DNA sequencer. C1 NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP SHOUKRY, S (reprint author), YORK UNIV,DEPT BIOL,4700 KEELE ST,N YORK M3J 1P3,ONTARIO,CANADA. NR 29 TC 5 Z9 5 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1991 VL 12 IS 11 BP 2089 EP 2092 DI 10.1093/carcin/12.11.2089 PG 4 WC Oncology SC Oncology GA GP558 UT WOS:A1991GP55800017 PM 1682064 ER PT J AU HRUSZKEWYCZ, AM DIPPLE, A AF HRUSZKEWYCZ, AM DIPPLE, A TI BYPASS OF A HYDROCARBON ADDUCT IN AN OLIGONUCLEOTIDE TEMPLATE MEDIATED BY MISPAIRING ADJACENT TO THE ADDUCT SO CARCINOGENESIS LA English DT Note ID INVITRO DNA-SYNTHESIS; ESCHERICHIA-COLI; DIOL-EPOXIDE; MOUSE SKIN; SITES; BENZOPYRENE; DEOXYGUANOSINE; DEOXYADENOSINE; CARCINOGENESIS; MUTAGENESIS AB The action of DNA polymerase (Sequenase Version 2.0) on an oligonucleotide template containing a 7-bromomethylbenz[a]anthracene-deoxyadenosine adduct flanked by thymidine residues was investigated. The polymerase incorporated deoxyadenosine or deoxyguanosine residues opposite the thymidine 3' to the adduct with similar efficiencies. Whereas the normal A.T base pair led to arrest of polymerase progression along the template, formation of the G.T mismatch allowed incorporation of thymidine opposite the adduct and further primer extension. This mispair-mediated bypass was also seen with AMV reverse transcriptase and may represent a novel mechanism for overcoming the replication block of a bulky carcinogen-DNA adduct. RP HRUSZKEWYCZ, AM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 18 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1991 VL 12 IS 11 BP 2185 EP 2187 DI 10.1093/carcin/12.11.2185 PG 3 WC Oncology SC Oncology GA GP558 UT WOS:A1991GP55800033 PM 1718621 ER PT J AU LIPPINCOTTSCHWARTZ, J YUAN, L TIPPER, C AMHERDT, M ORCI, L KLAUSNER, RD AF LIPPINCOTTSCHWARTZ, J YUAN, L TIPPER, C AMHERDT, M ORCI, L KLAUSNER, RD TI BREFELDIN-AS EFFECTS ON ENDOSOMES, LYSOSOMES, AND THE TGN SUGGEST A GENERAL MECHANISM FOR REGULATING ORGANELLE STRUCTURE AND MEMBRANE TRAFFIC SO CELL LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; TRANS-GOLGI NETWORK; ENDOPLASMIC-RETICULUM; IMMUNOELECTRON MICROSCOPY; INTRACELLULAR-TRANSPORT; CARCINOMA A431-CELLS; SECRETORY PROTEINS; PLASMA-MEMBRANE; RAT PANCREAS; TRANSFERRIN AB Addition of brefeldin A (BFA) to most cells results in both the formation of extensive, uncoated membrane tubules through which Golgi components redistribute into the ER and the failure to transport molecules out of this mixed ER/Golgi system. In this study we provide evidence that suggests BFA's effects are not limited to the Golgi apparatus but are reiterated throughout the central vacuolar system. Addition of BFA to cells resulted in the tubulation of the endosomal system, the trans-Golgi network (TGN), and lysosomes. Tubule formation of these organelles was specific to BFA, shared near identical pharmacologic characteristics as Golgi tubules and resulted in targeted membrane fusion. Analogous to the mixing of the Golgi with the ER during BFA treatment, the TGN mixed with the recycling endosomal system. This mixed system remained functional with normal cycling between plasma membrane and endosomes, but traffic between endosomes and lysosomes was impaired. C1 UNIV GENEVA,INST HISTOL & EMBRYOL,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. RP LIPPINCOTTSCHWARTZ, J (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 48 TC 680 Z9 684 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 1 PY 1991 VL 67 IS 3 BP 601 EP 616 DI 10.1016/0092-8674(91)90534-6 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GN664 UT WOS:A1991GN66400016 PM 1682055 ER PT J AU KASPRZAK, KS AF KASPRZAK, KS TI THE ROLE OF OXIDATIVE DAMAGE IN METAL CARCINOGENICITY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID SUPEROXIDE-DISMUTASE ACTIVITY; HYDROXYL RADICAL FORMATION; HAMSTER OVARY CELLS; HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; FERRIC NITRILOTRIACETATE; NICKEL SUBSULFIDE; DNA DAMAGE; DEOXYRIBONUCLEIC-ACID; POLYMORPHONUCLEAR LEUKOCYTES RP KASPRZAK, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 146 TC 188 Z9 193 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV-DEC PY 1991 VL 4 IS 6 BP 604 EP 615 DI 10.1021/tx00024a002 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA GR729 UT WOS:A1991GR72900003 PM 1807443 ER PT J AU BISHOP, RE MOSCHEL, RC AF BISHOP, RE MOSCHEL, RC TI POSITIONAL EFFECTS ON THE STRUCTURE AND STABILITY OF ABBREVIATED H-RAS DNA-SEQUENCES CONTAINING O-6-METHYLGUANINE RESIDUES AT CODON-12 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CIRCULAR-DICHROISM; MUTAGENESIS; TRANSITIONS; REPAIR; SITE; CARCINOGENESIS; EQUILIBRIUM; METHYLUREA; ACTIVATION; MISMATCHES AB Activation of the H-ras protooncogene in rats by methylating carcinogens results from a G-to-A transition mutation at the second position of codon 12 (GGA), presumably due to formation of an O6-methylguanine (m6G) at this position. A similar transition at the first position of codon 12 appears not to occur in vivo. To study the possible structural basis for this bias in mutation, we synthesized a series of 11-base H-ras sequences [e.g., 5'-d(CGCTG*G*AGGCG)-3' and two complementary strands] containing an m6G at the first, second, or both positions of codon 12 (i.e., G* = m6G). The results of solution chemical studies indicated that the individual strands formed stable hairpin structures among which that containing m6G at the second position of codon 12 was most stable. Further, the DNA duplex with m6G at the second position was significantly more stable than that with m6G at the first position, and under certain conditions, it was more stable than the unmodified duplex as well. It is possible that such a difference in stability might lead to more ready recognition of an m6G at the first position by repair proteins, and this could contribute to the apparent site specificity of mutation by methylating carcinogens at codon 12 of the H-ras gene. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 39 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV-DEC PY 1991 VL 4 IS 6 BP 647 EP 654 DI 10.1021/tx00024a009 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA GR729 UT WOS:A1991GR72900010 PM 1807448 ER PT J AU FEUERSTEIN, IM MARTIN, P SIMON, TR AF FEUERSTEIN, IM MARTIN, P SIMON, TR TI HYPOXIA AND CYANOSIS IN ALPHA-1-ANTITRYPSIN DEFICIENCY - CIRRHOSIS AS AN UNUSUAL ETIOLOGIC FACTOR SO CHEST LA English DT Article ID PULMONARY ARTERIOVENOUS-MALFORMATIONS; ALPHA1 ANTITRYPSIN DEFICIENCY; ALPHA1-ANTITRYPSIN DEFICIENCY; LIVER-DISEASE; RADIONUCLIDE METHOD; PROTEASE INHIBITOR; LUNG-DISEASE; EMPHYSEMA; HYPOXEMIA; TRANSPLANTATION AB A patient with type PiZZ alpha-1-antitrypsin deficiency was found to have severe hypoxia despite normal pulmonary function testing and a normal chest radiograph. A nuclear medicine ventilation-perfusion study revealed a right-to-left shunt. Computed tomography showed minimal bleb formation, no diffuse changes, and hepatic changes of cirrhosis with portal hypertension. No nodular pulmonary masses or enlarged peripheral pulmonary vessels were found. The diagnosis of diffuse intrapulmonic arteriovenous shunts ("pulmonary spiders of cirrhosis") was suggested and then confirmed with a dynamic radionuclide flow study. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD. GEORGETOWN UNIV HOSP,DEPT RADIOL,WASHINGTON,DC 20007. NR 54 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1991 VL 100 IS 5 BP 1323 EP 1327 DI 10.1378/chest.100.5.1323 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA GN722 UT WOS:A1991GN72200031 PM 1935289 ER PT J AU URSELL, PC BYRNE, JM FEARS, TR STROBINO, BA GERSONY, WM AF URSELL, PC BYRNE, JM FEARS, TR STROBINO, BA GERSONY, WM TI GROWTH OF THE GREAT-VESSELS IN THE NORMAL HUMAN FETUS AND IN THE FETUS WITH CARDIAC DEFECTS SO CIRCULATION LA English DT Article DE GREAT VESSELS; FETAL CARDIAC DEVELOPMENT ID CONGENITAL HEART-DISEASE AB Background. There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages. Methods and Results. To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter. Conclusions. During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range. C1 COLUMBIA UNIV,GERTRUDE H SERGIEVSKY CTR,DEPT PATHOL,NEW YORK,NY 10027. COLUMBIA UNIV,GERTRUDE H SERGIEVSKY CTR,DEPT PEDIAT,NEW YORK,NY 10027. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 17 TC 23 Z9 28 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1991 VL 84 IS 5 BP 2028 EP 2033 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GN522 UT WOS:A1991GN52200016 PM 1934377 ER PT J AU LOMPRE, AM LAMBERT, F LAKATTA, EG SCHWARTZ, K AF LOMPRE, AM LAMBERT, F LAKATTA, EG SCHWARTZ, K TI EXPRESSION OF SARCOPLASMIC-RETICULUM CA-2+-ATPASE AND CALSEQUESTRIN GENES IN RAT-HEART DURING ONTOGENIC DEVELOPMENT AND AGING SO CIRCULATION RESEARCH LA English DT Article DE SARCOPLASMIC RETICULUM; CA-2+-ATPASE; CALSEQUESTRIN; ONTOGENIC DEVELOPMENT; AGING; RAT HEART ID MUSCLE CELL-CULTURES; AMINO-ACID SEQUENCE; PIG SMOOTH-MUSCLE; HEAVY-CHAIN GENES; SKELETAL-MUSCLE; MESSENGER-RNA; CA-2+ PUMP; MOLECULAR-CLONING; CONTRACTION DURATION; PRESSURE OVERLOAD AB Little is known concerning the molecular mechanisms responsible for changes in sarcoplasmic reticulum (SR) function during ontogenic development and aging except that the amount of SR Ca2+-ATPase mRNA varies in these conditions. The aim of the present work was to determine whether SR maturation requires expression of specific isoforms and synchronous accumulation of mRNAs encoding proteins located in SR. Thus, we have studied expression of SR Ca2+-ATPase and calsequestrin genes in the rat at different developmental stages from 14 fetal days to 24 months of age. Analysis of alternative splicing of the major Ca2+-ATPase gene expressed in heart by nuclease S1 mapping led us to conclude that the Ca2+-ATPase gene expressed in heart was not differentially spliced during ontogenic development and senescence. A single calsequestrin mRNA isoform was also detected in rat heart whatever the developmental stage. The amount of specific mRNA was then measured by dot blot and normalized to 18S ribosomal RNA or to myosin heavy chain mRNA. The amount of Ca2+-ATPase mRNA relative to 18S RNA increases substantially at the end of fetal life and in the early postnatal period (9.5 +/- 0.5% in the 14-15-day fetus versus 99 +/- 7% in the 4-day-old rat). A stable high level is observed during adulthood. In aged rats (24 months), Ca2+-ATPase mRNA represents only 44.6% the amount observed in young adults (1-2 months). In the fetal-neonatal period the increase in Ca2+-ATPase mRNA concentration is parallel to the increase in myosin heavy chain mRNA concentration, but during senescence the two mRNAs do not evolve in parallel. The concentration of calsequestrin mRNA also peaks at day 4 but is equally abundant in fetal, adult, and senescent rats, which supports and extends previous observations showing that, during maturation of SR, calsequestrin is synthesized earlier than ATPase. Our results indicate that maturation of SR, which is in part responsible for changes in relaxation rate, does not involve a Ca2+-ATPase and calsequestrin isoform switch but, rather, changes in the concentration of single isoforms. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. HOP LARIBOISIERE,INSERM,U127,F-75475 PARIS 10,FRANCE. RP LOMPRE, AM (reprint author), ECOLE POLYTECH PALAISEAU,ECOLE NATL SUPER TECH AVANCEES,LOA,INSERM,U275,CTR YVETTE,F-91120 PALAISEAU,FRANCE. RI LOMPRE, Anne-Marie/H-2872-2013 NR 60 TC 161 Z9 164 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV PY 1991 VL 69 IS 5 BP 1380 EP 1388 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA GN521 UT WOS:A1991GN52100021 PM 1834363 ER PT J AU BLAESE, RM AF BLAESE, RM TI PROGRESS TOWARD GENE-THERAPY SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT JEFFREY MODELL IMMUNODEFICIENCY SYMP : NEW CONCEPTS IN IMMUNODEFICIENCY DISEASE CY APR 18-19, 1990 CL MT SINAI MED CTR, NEW YORK, NY SP JEFFREY MODELL FDN HO MT SINAI MED CTR ID TUMOR-INFILTRATING LYMPHOCYTES; DEAMINASE DEFICIENCY; CELLS; ADENOSINE; IMMUNOTHERAPY; MELANOMA; MOUSE RP BLAESE, RM (reprint author), NCI,METAB BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1991 VL 61 IS 2 BP S47 EP S55 DI 10.1016/S0090-1229(05)80037-6 PN 2 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA GM402 UT WOS:A1991GM40200007 PM 1934613 ER PT J AU GALLIN, JI AF GALLIN, JI TI INTERFERON-GAMMA IN THE TREATMENT OF THE CHRONIC GRANULOMATOUS DISEASES OF CHILDHOOD SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT JEFFREY MODELL IMMUNODEFICIENCY SYMP : NEW CONCEPTS IN IMMUNODEFICIENCY DISEASE CY APR 18-19, 1990 CL MT SINAI MED CTR, NEW YORK, NY SP JEFFREY MODELL FDN HO MT SINAI MED CTR ID NADPH OXIDASE; GENE; NEUTROPHILS; EXPRESSION; CLONING RP GALLIN, JI (reprint author), NIAID,CLIN INVEST LAB,BACTERIAL DIS SECT,BETHESDA,MD 20892, USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1991 VL 61 IS 2 BP S100 EP S105 DI 10.1016/S0090-1229(05)80044-3 PN 2 PG 6 WC Immunology; Pathology SC Immunology; Pathology GA GM402 UT WOS:A1991GM40200014 PM 1934607 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI LYMPHOKINE RECEPTOR-DIRECTED THERAPY - A MODEL FOR IMMUNE INTERVENTION IN LEUKEMIA, AUTOIMMUNITY, AND IMMUNODEFICIENCY SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT JEFFREY MODELL IMMUNODEFICIENCY SYMP : NEW CONCEPTS IN IMMUNODEFICIENCY DISEASE CY APR 18-19, 1990 CL MT SINAI MED CTR, NEW YORK, NY SP JEFFREY MODELL FDN HO MT SINAI MED CTR ID T-CELL LEUKEMIA; AFFINITY INTERLEUKIN-2 RECEPTOR; TROPICAL SPASTIC PARAPARESIS; VIRUS TYPE-I; MONOCLONAL-ANTIBODY; PSEUDOMONAS EXOTOXIN; GROWTH-FACTOR; TAC ANTIGEN; HTLV-I; HUMANIZED ANTIBODY RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BETHESDA,MD 20892, USA. NR 47 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1991 VL 61 IS 2 BP S37 EP S46 DI 10.1016/S0090-1229(05)80036-4 PN 2 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA GM402 UT WOS:A1991GM40200006 PM 1934612 ER PT J AU MUZAFFAR, A HAMEL, E BAI, R BROSSI, A AF MUZAFFAR, A HAMEL, E BAI, R BROSSI, A TI SYNTHESIS AND TUBULIN INTERACTION OF THIOCOLCHICINES CONTAINING AN ISOTHIOCYANATO GROUP - SYNTHESIS OF C(2)-DEUTERATED AND C(2)-C-14-LABELED 7-ISOTHIOCYANATODEACETAMIDOTHIOCOLCHICINE SO COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS LA English DT Article ID 3-DEMETHYLTHIOCOLCHICINE; DERIVATIVES; RECEPTORS; BINDING; LIGANDS; ETHER AB Synthesis of isothiocyanato substituted thiocolchicines XI-XIV is described. Introduction of an isotope label is demonstrated with the deuterated isothiocyanate XII and the C-14-labeled analog XIII. These isothiocyanates inhibit tubulin Polymerization at low concentration. In addition, the C-14-labeled XIII forms covalent bond(s) with tubulin. Unfortunately, the covalent reaction while rapid, is not inhibited by preincubation of tubulin with colchicine. The covalent interaction of XIII with tubulin thus appears to be nonspecific, limiting its use as a marker of the colchicine binding site on tubulin. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP MUZAFFAR, A (reprint author), NIDDK,STRUCT BIOL LAB,NAT PROD SECT,BETHESDA,MD 20892, USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU INST ORGANIC CHEM AND BIOCHEM PI PRAGUE 6 PA ACAD OF SCI CZECH REPUBLIC FLEMINGOVO NAM 2, PRAGUE 6, CZECH REPUBLIC 166 10 SN 0010-0765 J9 COLLECT CZECH CHEM C JI Collect. Czech. Chem. Commun. PD NOV PY 1991 VL 56 IS 11A BP 2306 EP 2312 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA GU454 UT WOS:A1991GU45400010 ER PT J AU BAYNE, K AF BAYNE, K TI PROVIDING ENVIRONMENTAL ENRICHMENT TO CAPTIVE PRIMATES SO COMPENDIUM ON CONTINUING EDUCATION FOR THE PRACTICING VETERINARIAN LA English DT Review AB The complex nature of nonhuman primates is well illustrated by the broad range of behaviors exhibited by this diverse group of animals. Each species has specific abilities that it has developed to survive in its particular ecological niche. Removal of an animal from its dynamic, stimulating natural environment to a less complex captive environment can result in that animal exhibiting behaviors considered abnormal for that species. This abnormality may be the manifestation of behaviors of a different and maladaptive pattern (or quality) than is normal for the free-ranging animal. Also, an animal may demonstrate a behavior that is qualitatively normal but occurs at an abnormal frequency. The appearance of such behaviors can be considered a sign of some degree of psychological distress. The most efficient approach to managing psychological disturbances is similar to that used for physical illnesses; a preventive, diagnostic, and therapeutic approach commonly used for managing animals with physical disorders can be successfully applied to animals with psychological disorders. Consideration of psychological disorders in a clinical framework encourages a more scientific approach to their elimination. RP BAYNE, K (reprint author), NIH,VET RESOURCES PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 1 U2 6 PU VETERINARY LEARNING SYSTEMS PI TRENTON PA 425 PHILLIPS BLVD #100, TRENTON, NJ 08618 SN 0193-1903 J9 COMP CONT EDUC PRACT JI Compend. Contin. Educ. Pract. Vet. PD NOV PY 1991 VL 13 IS 11 BP 1689 EP & PG 0 WC Veterinary Sciences SC Veterinary Sciences GA GP759 UT WOS:A1991GP75900003 ER PT J AU POLLACK, MM RUTTIMANN, UE ALEXANDER, SR BACHULIS, AC CLARKE, N AF POLLACK, MM RUTTIMANN, UE ALEXANDER, SR BACHULIS, AC CLARKE, N TI IMPROVED OUTCOMES FROM TERTIARY CENTER PEDIATRIC INTENSIVE-CARE - A STATEWIDE COMPARISON OF TERTIARY AND NONTERTIARY CARE FACILITIES - REPLY SO CRITICAL CARE MEDICINE LA English DT Letter ID TRAUMA; FAILURE; SCORE; TRISS C1 NIH,INST DENT,DIAGNOST SYST BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,CHILDRENS MED CTR DALLAS,DEPT PEDIAT,DALLAS,TX 75230. PORTLAND COMMUNITY COLL,INST CONTINUING EDUC HLTH CARE PROFESS,PORTLAND,OR. OREGON HLTH DEPT,EMERGENCY MED SERV,PORTLAND,OR. RP POLLACK, MM (reprint author), GEORGE WASHINGTON UNIV,CHILDRENS HOSP,NATL MED CTR,SCH MED,WASHINGTON,DC 20010, USA. NR 10 TC 0 Z9 0 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1991 VL 19 IS 11 BP 1453 EP 1454 DI 10.1097/00003246-199111000-00026 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA GN718 UT WOS:A1991GN71800026 ER PT J AU FARRAR, WL KORNER, M CLOUSE, KA AF FARRAR, WL KORNER, M CLOUSE, KA TI CYTOKINE REGULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS EXPRESSION SO CYTOKINE LA English DT Review DE AIDS; HIV; CYTOKINES ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; CENTRAL NERVOUS-SYSTEM; HTLV-III LAV; NF-KAPPA-B; VIRAL-ANTIGEN STIMULATION; DEFICIENCY SYNDROME AIDS; HUMAN INTERFERON-GAMMA; INFECTED T-CELLS C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20014. LAB IMMUNOL CELLULAIRE,PARIS,FRANCE. RP FARRAR, WL (reprint author), NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 560,ROOM 21-89A,FREDERICK,MD 21702, USA. NR 156 TC 30 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 1991 VL 3 IS 6 BP 531 EP 542 DI 10.1016/1043-4666(91)90479-W PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA GW948 UT WOS:A1991GW94800001 PM 1790301 ER PT J AU GOTLIEB, WH TAKACS, L FINCH, LR KOPP, W WEISSMAN, AM DURUM, SK AF GOTLIEB, WH TAKACS, L FINCH, LR KOPP, W WEISSMAN, AM DURUM, SK TI CD8 GAMMA-DELTA CELLS - PRESENCE IN THE ADULT-RAT THYMUS AND GENERATION INVITRO FROM CD4-/CD8- THYMOCYTES IN THE PRESENCE OF INTERLEUKIN-2 SO CYTOKINE LA English DT Article DE DIFFERENTIATION; IL-2; RAT; TCR; THYMUS ID MRC OX-44 ANTIGEN; T-CELLS; MONOCLONAL-ANTIBODY; INTRAEPITHELIAL LYMPHOCYTES; IMMATURE THYMOCYTES; CYTOLYTIC ACTIVITY; MURINE THYMOCYTES; IL-2 RECEPTORS; ALPHA-CHAIN; EXPRESSION C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NIH,DIV CANC BIOL & DIAG,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74102] NR 55 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 1991 VL 3 IS 6 BP 598 EP 608 DI 10.1016/1043-4666(91)90487-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA GW948 UT WOS:A1991GW94800009 PM 1838702 ER PT J AU FALTYNEK, CR PRINCLER, GL SCHWABE, M AF FALTYNEK, CR PRINCLER, GL SCHWABE, M TI DIFFERENTIAL MODULATION OF 2 INTERFERON-ALPHA BINDING-PROTEINS ON A HUMAN LYMPHOBLASTOID CELL-LINE SO CYTOKINE LA English DT Article DE AFFINITY-CROSS-LINKING; INTERFERON; INTERFERON RECEPTOR; LIGAND BLOTTING; RECEPTOR MODULATION ID RECEPTOR EXPRESSION; DOWN-REGULATION; INTERNALIZATION; LYMPHOCYTES; THERAPY; SITES C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 26 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 1991 VL 3 IS 6 BP 627 EP 635 DI 10.1016/1043-4666(91)90490-5 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA GW948 UT WOS:A1991GW94800012 PM 1838703 ER PT J AU ROBINSON, SD SILBERSTEIN, GB ROBERTS, AB FLANDERS, KC DANIEL, CW AF ROBINSON, SD SILBERSTEIN, GB ROBERTS, AB FLANDERS, KC DANIEL, CW TI REGULATED EXPRESSION AND GROWTH INHIBITORY EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN MOUSE MAMMARY-GLAND DEVELOPMENT SO DEVELOPMENT LA English DT Article DE TGF-BETA; ISOFORMS; MOUSE; NORTHERN HYBRIDIZATION; INSITU HYBRIDIZATION; MAMMARY GLAND; GROWTH REGULATION; MORPHOGENESIS ID DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; TGF-BETA; MYOGENIC DIFFERENTIATION; BIOLOGICAL-ACTIVITIES; EXTRACELLULAR-MATRIX; EMBRYO CHONDROCYTES; ADULT TISSUES; RNA; CELLS AB Transforming Growth Factor-beta-1 (TGF-beta-1) was previously shown to inhibit reversibly the growth of mouse mammary ducts when administered in vivo by miniature slow-release plastic implants. We now report a comparative analysis of three TGF-beta isoforms with respect to gene expression and localization of protein products within the mouse mammary gland. Our studies revealed overlapping expression patterns of TGF-beta-1, TGF-beta-2 and TGF-beta-3 within the epithelium of the actively-growing mammary end buds during branching morphogenesis, as well as within the epithelium of growth-quiescent ducts. However, TGF-beta-3 was the only isoform detected in myoepithelial progenitor cells (cap cells) of the growing end buds and myoepithelial cells of the mature ducts. During pregnancy, TGF-beta-2 and TGF-beta-3 transcripts increased to high levels, in contrast to TGF-beta-1 transcripts which were moderately abundant; TGF-beta-2 was significantly transcribed only during pregnancy. Molecular hybridization in situ revealed overlapping patterns of expression for the three TGF-beta isoforms during alveolar morphogenesis, but showed that, in contrast to the patterns of TGF-beta-1 and TGF-beta-2 expression, TGF-beta-3 is expressed more heavily in ducts than in alveoli during pregnancy. Developing alveolar tissue and its associated ducts displayed striking TGF-beta-3 immunoreactivity which was greatly reduced during lactation. All three isoforms showed dramatically reduced expression in lactating tissue. The biological effects of active, exogenous TGF-beta-2 and TGF-beta-3 were tested with slow-release plastic implants. These isoforms, like TGF-beta-1, inhibited mammary ductal elongation in situ by causing the disappearance of the proliferating stem cell layer (cap cells) and rapid involution of ductal end buds. None of the isoforms were active in inhibiting alveolar morphogenesis. We conclude that under the limited conditions of these tests, the three mammalian isoforms are functionally equivalent. However, striking differences in patterns of gene expression and in the distribution of immunoreactive peptides suggest that TGF-beta isoforms may have distinct roles in mammary growth regulation, morphogenesis and functional differentiation. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP ROBINSON, SD (reprint author), UNIV CALIF SANTA CRUZ,DEPT BIOL,SINSHEIMER LABS,SANTA CRUZ,CA 95064, USA. FU NCI NIH HHS [CA 45231] NR 60 TC 202 Z9 204 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1991 VL 113 IS 3 BP 867 EP & PG 0 WC Developmental Biology SC Developmental Biology GA GT172 UT WOS:A1991GT17200015 PM 1821856 ER PT J AU PERRIS, R KROTOSKI, D BRONNERFRASER, M AF PERRIS, R KROTOSKI, D BRONNERFRASER, M TI COLLAGENS IN AVIAN NEURAL CREST DEVELOPMENT - DISTRIBUTION INVIVO AND MIGRATION-PROMOTING ABILITY INVITRO SO DEVELOPMENT LA English DT Article DE COLLAGENS; NEURAL CREST; AVIAN EMBRYO; CELL MIGRATION ID 3-DIMENSIONAL EXTRACELLULAR MATRICES; COLD-INSOLUBLE GLOBULIN; CELL-MIGRATION; V COLLAGEN; ANCHORING FIBRILS; VII COLLAGEN; MONOCLONAL-ANTIBODIES; BASAL LAMINA; CHICK-EMBRYO; IX COLLAGEN AB This study examines the spatiotemporal distribution of collagen (Col) types I-V and IX during neural crest development in vivo and their ability to support neural crest cell movement in vitro. Col I, III and IV were widespread throughout the embryo, including the neural crest migratory pathways, whereas Col II, V and IX preferentially localized to regions from which migrating neural crest cells were absent. Col I-IV and IX occurred both in association with basement membranes and within interstitial matrices, whereas Col V only was detected in juxtaposition to basement membranes. Although initially distributed throughout the rostrocaudal extent of the somitic sclerotome, Col I and III rearranged to the caudal portion with progressive neural crest cell migration through the rostral portion of the sclerotome. This rearrangement does not occur in neural crest-ablated embryos, suggesting that it is a direct consequence of neural crest cell migration. The perinotochordal matrix, avoided by neural crest cells, contained a metameric Col II/IX immunoreactivity along the rostrocaudal axis which alternated with that of Col I and III. In contrast, Col IV and V were not observed in this matrix, but lined the basement membranes of the notochord and ventrolateral neural tube. To determine their functional significance for neural crest cell migration in vivo, purified collagens were tested for their ability to promote neural crest cell motility in vitro. Neural crest cell migration on isolated collagens was most pronounced on Col I and IV, whereas Col II, V and the triple-helical fragment of Col VII were unable to support cell motility. Substrata created by copolymerization of Col I and fibronectin, or Col I and laminin-nidogen, supported cell motility better than Col I alone, whereas both Col V and a cartilage-type chondroitin sulfate proteoglycan reduced cell movement on Col I. Fibronectin bound to pre-immobilized monomeric Col I, II or V had a reduced ability to support neural crest cell movement when compared to fibronectin alone. A similar reduction was seen for Col IV bound to the low density heparan sulfate proteoglycan from the EHS mouse tumor. The results demonstrate that Col I-IX are differentially distributed in the early avian embryo. During neural crest development several of these collagens undergo dynamic reorganizations that correlate with the migration of neural crest cells. Furthermore, various collagens possess distinct abilities to support neural crest cell migration in vitro, and their migration-promoting activity can be modulated by their conformation and/or association with other matrix components. C1 NIH,FOGARTY INT CTR,BETHESDA,MD 20892. RP PERRIS, R (reprint author), UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717, USA. FU NICHD NIH HHS [HD15527] NR 54 TC 65 Z9 66 U1 0 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 NOV PY 1991 VL 113 IS 3 BP 969 EP & PG 0 WC Developmental Biology SC Developmental Biology GA GT172 UT WOS:A1991GT17200024 PM 1821863 ER PT J AU LYONS, GE MUHLEBACH, S MOSER, A MASOOD, R PATERSON, BM BUCKINGHAM, ME PERRIARD, JC AF LYONS, GE MUHLEBACH, S MOSER, A MASOOD, R PATERSON, BM BUCKINGHAM, ME PERRIARD, JC TI DEVELOPMENTAL REGULATION OF CREATINE-KINASE GENE-EXPRESSION BY MYOGENIC FACTORS IN EMBRYONIC MOUSE AND CHICK SKELETAL-MUSCLE SO DEVELOPMENT LA English DT Article DE B-CREATINE KINASE; M-CREATINE KINASE; CHICK EMBRYO; MOUSE EMBRYO; MYOGENIC FACTORS; INSITU HYBRIDIZATION; SKELETAL MUSCLE DEVELOPMENT ID DNA-BINDING; CELL-CULTURES; MESSENGER-RNA; PROMOTER REGION; MYC HOMOLOGY; SUBUNITS-M; ENHANCER; MYOD; ISOENZYMES; MYOBLASTS AB The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis. Using isoform-specific S-35-labeled antisense cRNA probes for in situ hybridization, we have detected BCK mRNAs in embryonic mouse and chick myotomes, the first skeletal muscle masses to form in developing embryos. These transcripts are detectable as soon as myotomes are morphologically distinguishable. BCK is expressed at high levels in both skeletal and cardiac muscle in mouse and chick embryos. In the mouse, BCK transcript levels fall off rapidly in striated muscle shortly after the onset of MCK gene expression. The M isoform of creatine kinase (MCK), the striated muscle-specific isoform, is expressed later than BCK. In the mouse, BCK transcripts are expressed in myotomes at 8.5 days post coitum (p.c.), but MCK transcripts are not detected before 13 days p.c. In the chick, BCK mRNAs are present at Hamburger-Hamilton stage 13, but MCK mRNAs are not detected before stage 19. We have compared the patterns of expression of the CK genes with those of myogenic differentiation factor genes, which are thought to regulate skeletal muscle-specific gene expression. In the chick, both CMD1, first detected at stage 13, and myogenin, first detected at stage 15, are present prior to MCK, which begins to be expressed at stage 19. Unlike the mouse embryo, CMD1, the chick homologue of MyoD1, is expressed before chick myogenin. In the mouse, myogenin, first detected at 8.5 days p.c., is expressed at the same time as BCK in myotomes. Both myogenin and MyoD1, which begins to be detected two days later than myogenin, are expressed at least two days before MCK. It has been proposed that the myogenic factors, MyoD1 and myogenin, directly regulate MCK gene expression in the mouse by binding to its enhancer. However, our results show that MCK transcripts are not detected until well after MyoD1 and myogenin mRNAs are expressed, suggesting that these factors by themselves are not sufficient to initiate MCK gene expression. C1 INST PASTEUR,DEPT MOLEC BIOL,CNRS,UA 1148,28 RUE DOCTEUR ROUX,F-75724 PARIS 15,FRANCE. SWISS FED INST TECHNOL,INST CELLULAR BIOL,CH-8093 ZURICH,SWITZERLAND. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 57 TC 96 Z9 97 U1 0 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 NOV PY 1991 VL 113 IS 3 BP 1017 EP 1029 PG 13 WC Developmental Biology SC Developmental Biology GA GT172 UT WOS:A1991GT17200028 PM 1668275 ER PT J AU PERANTONI, AO WILLIAMS, CL LEWELLYN, AL AF PERANTONI, AO WILLIAMS, CL LEWELLYN, AL TI GROWTH AND BRANCHING MORPHOGENESIS OF RAT COLLECTING DUCT ANLAGEN IN THE ABSENCE OF METANEPHROGENIC MESENCHYME SO DIFFERENTIATION LA English DT Article ID EPITHELIAL-CELLS; NEPHRO-BLASTOMA; COLLAGEN-III; FACTOR-BETA; LUNG; CULTURE; DIMETHYLNITROSAMINE; INDUCTION; TUMORS; GLYCOSAMINOGLYCANS AB The growth and differentiation of the epithelium in many tissues is mediated by interactions with the adjacent mesenchyme, but the mechanisms responsible remain undefined. To identify the factors involved in the growth and branching morphogenesis of ureteric bud, which is the collecting duct anlagen, buds from 13-gestation-day rat embryos were separated from the metanephrogenic mesenchyme and explanted to culture dishes coated with gelled type I collagen in a defined medium. Under these conditions buds attached to the substrate and grew out without indication of cell senescence. When buds were instead suspended in gelled type I collagen, branching morphogenesis was observed despite the absence of mesenchyme although it was not as extensive as in vivo. Since growth occurred much more slowly in culture than expected, culture conditions were varied in attempts to accelerate the process. Despite extensive screening of matrices and growth factors, only epidermal and endothelial cell growth factors stimulated growth to a significant extent. Transforming growth factor-beta, on the other hand, was a potent inhibitor of growth. Homogenates from tumors that caricature metanephrogenic mesenchyme were highly mitogenic for bud cells and, thus, will be a source of material for characterizing regulatory factors involved in renal growth. These studies show that growth and branching morphogenesis of the ureteric bud can occur without direct cell-cell interactions with the metanephrogenic mesenchyme and that matrices and factors secreted by the mesenchyme may mediated these activities in vivo. C1 NATL CANC INST,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP PERANTONI, AO (reprint author), UNIV COLORADO,SCH MED,DEPT PATHOL,BOX B-216,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 39 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD NOV PY 1991 VL 48 IS 2 BP 107 EP 113 DI 10.1111/j.1432-0436.1991.tb00249.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GR751 UT WOS:A1991GR75100007 PM 1773916 ER PT J AU MCMAHON, TF BIRNBAUM, LS AF MCMAHON, TF BIRNBAUM, LS TI AGE-RELATED-CHANGES IN DISPOSITION AND METABOLISM OF BENZENE IN MALE C57BL/6N MICE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID EXPOSURE; RATS AB Benzene disposition and metabolism were examined as a function of age in male C57BL/6N mice aged 3 and 18 months. Mice received a single oral dose of either 10 or 200 mg/kg C-14-benzene (approximately 25-mu-Ci/kg). Excretion of C-14-derived benzene radioactivity (RA) was monitored in urine, feces, and as exhaled (CO2)-C-14 from 0 to 72 hr, and as exhaled unmetabolized benzene from 0 to 6 hr. At 10 mg/kg C-14-benzene, urinary elimination was the major route of excretion in both 3- and 18-month mice. Urinary excretion of C-14-derived benzene RA was significantly decreased in 18- vs. 3-month mice at 4, 6, 24, and 48 hr, while fecal excretion was significantly increased at 72 hr. Elimination of C-14-benzene as (CO2)-C-14 and unmetabolized C-14-benzene was also increased in 18- vs. 3-month mice at this dose. Hydroquinone glucuronide (HQG), phenylsulfate (PS), and muconic acid (MUC) were the major urinary metabolites at 10 mg/kg C-14-benzene in both 3- and 18-month mice, representing approximately 40, 28, and 15% of an administered dose of C-14-benzene. Smaller amounts of phenyl glucuronide (4.0%), pre-phenyl mercapturic acid (1.2%), and catechol glucuronide (0.5%) were also detected. No significant differences were found with age in the percentage of an administered dose of benzene excreted as the various metabolites at 10 mg/kg. At 200 mg/kg C-14-benzene, the total percentage of C-14-derived benzene RA eliminated in urine within 72 hr was not significantly different with age, but elimination at early time points (4, 6, and 8 hr) was significantly decreased in 18- vs. 3-month mice. Fecal elimination was significantly increased at 48 and 72 hr in 18-month mice, whereas excretion of unmetabolized benzene was decreased in this age group. The percentage of water-soluble metabolites as MUC at 200 mg/kg C-14-benzene was significantly decreased in 3- and 18-month mice, whereas the percentage as HOG remained constant with age at this dose. In contrast, formation of phenyl glucuronide was significantly increased with dose in 3-month mice, whereas PS formation was significantly increased with dose in 18-month mice. The results of these experiments indicate that total metabolism of benzene as well as metabolism to specific metabolites is affected by aging. C1 US EPA,ENVIRONM TOXICOL BRANCH,MD-66,RES TRIANGLE PK,NC 27711. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. NR 14 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV-DEC PY 1991 VL 19 IS 6 BP 1052 EP 1057 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ609 UT WOS:A1991GQ60900007 PM 1687010 ER PT J AU MATHEWS, JM PARKER, MK MATTHEWS, HB AF MATHEWS, JM PARKER, MK MATTHEWS, HB TI METABOLISM AND DISPOSITION OF DIETHYLENE GLYCOL IN RAT AND DOG SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID TOXICITY; ETHYLENE AB The disposition of carbon-14-labeled diethylene glycol (DEG) was determined in rats after oral, iv, and dermal administration, and in dogs after oral administration. Oral administration of DEG to rats was by gavage of 50 or 5000 mg/kg doses, or by provision of 0.3, 1.0, and 3.0% in drinking water. Oral doses were well absorbed and excreted primarily (approximately 80%) in urine within 24 hr of administration. Greater than half of the dose was excreted unchanged, with 10-30% of the dose appearing as a single metabolite. The metabolite was isolated and characterized by C-13-NMR to be 2-(hydroxy) ethoxyacetic acid (HEAA). Confirmation of identity was provided by synthesis of HEAA and comparison of its NMR spectra and chromatographic behavior with those of the metabolite. Intravenous doses (50 mg/kg) were eliminated by the same routes and at the same rates as those administered orally and exhibited the same metabolic profile. The fate of oral doses of DEG administered to dogs (500 mg/kg) was similar to that of DEG in rats, with about 30% of the administered dose being excreted in urine as HEAA. DEG slowly penetrated the skin of rats after application of 50 mg to a 12-cm2 area. Only about 10% of the dose was absorbed in 72 hr of exposure, and the absorbed dose appeared to have the same fate as doses administered iv or orally. In all studies with rats, excretion of radio-label in feces and persistence in tissues were low. The highest percentage of conversion to (CO2)-C-14 was 7%, found for doses of 0.3% DEG in drinking water. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP MATHEWS, JM (reprint author), RES TRIANGLE INST,CTR BIOORGAN CHEM,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-65137] NR 15 TC 31 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV-DEC PY 1991 VL 19 IS 6 BP 1066 EP 1070 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ609 UT WOS:A1991GQ60900009 PM 1687012 ER PT J AU PARMAR, D BURKA, LT AF PARMAR, D BURKA, LT TI METABOLISM AND DISPOSITION OF CYCLOHEXANONE OXIME IN MALE F344 RATS SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CYCLOHEXYLAMINE; MUTAGENICITY; DEAMINATION; CYCLAMATE; TOXICITY AB Cyclohexanone oxime (CHOX), an intermediate used in the synthesis of Polycaprolactam/Nylon, was found to be rapidly absorbed and cleared from the body within 24 hours after a single oral administration of 1, 10 and 30 mg/kg of [C-14]-CHOX to the adult male Fischer rats. The majority of the CHOX derived radioactivity (65-90% of the dose) was excreted in the urine. Elimination in the feces accounted for 5-10% of the dose and very low levels of radioactivity (2-3%) were retained in the tissues 24 hours after exposure. After iv administration of 1 mg/kg of [C-14]-CHOX, the oxime was rapidly cleared from plasma with half-lives of 1.6 (alpha phase) and 18.2 min (beta phase). However, when CHOX was applied dermally (30 mg/kg), only about 4-5% of the dose was recovered in urine, feces and the tissues. The majority of the dose volatilized from the skin surface. However, the absorbed oxime was readily distributed and excreted, and its metabolic fate was no different than observed after oral administrations. HPLC analysis of urine showed that the majority of the radioactivity excreted was in the form of three metabolites, cyclohexylglucuronide and the monoglucuronides of cis- and trans-cyclohexane-1,2-diol. In vitro studies showed that these metabolites arise primarily by hydrolysis of the oxime to cyclohexanone which is then reduced to cyclohexanol and eliminated as the glucuronide conjugate. The cyclohexanol, in turn could be metabolized to cis- and trans-cyclohexane-1,2-diols, which are excreted as their monoglucuronides. C1 NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709. NR 20 TC 18 Z9 18 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV-DEC PY 1991 VL 19 IS 6 BP 1101 EP 1107 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ609 UT WOS:A1991GQ60900014 PM 1687017 ER PT J AU WIRTH, PJ LUO, LD FUJIMOTO, Y BISGAARD, HC OLSON, AD AF WIRTH, PJ LUO, LD FUJIMOTO, Y BISGAARD, HC OLSON, AD TI THE RAT-LIVER EPITHELIAL (RLE) CELL PROTEIN DATABASE SO ELECTROPHORESIS LA English DT Article ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; DIMENSIONAL GEL-ELECTROPHORESIS; COMPUTER-ANALYSIS; PURIFICATION; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE; IDENTIFICATION; EXPRESSION; EPIDERMIS; EXPOSURE; CULTURE AB Computer databases of rat liver epithelial (RLE) cellular polypeptides have been established using high resolution two-dimensional gel electrophoresis and computer-assisted analysis. Databases have been constructed utilizing both [S-35]methionine- and [P-32]orthophosphate-labeled as well as silver-stained polypeptides from normal RLE cells. The RLE database, which contains both qualitative and quantitative annotations, includes experiments with normal, chemically and oncogene transformed as well as spontaneously transformed cell lines. A total of 2537 [S-35]methionine-labeled polypeptides from whole cell lysates (1920 acidic and 617 basic, separated in the first dimension using isoelectric focusing and nonequilibrium pH gradient electrophoresis, respectively) were analyzed and databases constructed using the Elsie 5 gel analysis system. To increase the "viewing window" and hence the usefulness of the RLE database, subcellular fractionation of whole cell preparations was performed and high resolution two-dimensional maps of the individual subcellular components were constructed. Databases representing 1229 cytosolic, 1539 acidic and 674 basic nuclear, 1746 membrane-associated, 415 mitochondrial, 773 in vitro translated and 350 phosphoproteins were established from these maps. The RLE databases contain the Elsie 5 identification number, protein name (if known), molecular weight and pI information, quantitative and spot shape data, and specific information regarding transformation-sensitive, growth-related (exponentially proliferating versus confluent) cell populations as well as those polypeptides modulated by specific growth factors. The RLE databases represent initial efforts toward the establishment of comprehensive databases of rat liver proteins and serve as a vital resource for on-going as well as future studies regarding the regulation of growth and differentiation as well as transformation of RLE cells. RP WIRTH, PJ (reprint author), NCI,EXPTL CARCINOGENESIS,BLDG 37,ROOM 3C28,BALTIMORE,MD 21211, USA. NR 52 TC 25 Z9 25 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1991 VL 12 IS 11 BP 931 EP 954 DI 10.1002/elps.1150121112 PG 24 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GY063 UT WOS:A1991GY06300007 PM 1794345 ER PT J AU CLARK, DJ WOLFFE, AP AF CLARK, DJ WOLFFE, AP TI SUPERHELICAL STRESS AND NUCLEOSOME-MEDIATED REPRESSION OF 5S RNA GENE-TRANSCRIPTION INVITRO SO EMBO JOURNAL LA English DT Article DE DNA SUPERCOILING; HISTONE OCTAMER; HISTONE TETRAMER; NUCLEOSOME-MEDIATED REPRESSION; 5S RNA GENE TRANSCRIPTION ID MINICHROMOSOMES ASSEMBLED INVITRO; XENOPUS-LAEVIS OOCYTES; RICH HISTONE KERNEL; POLYMERASE TRANSCRIBES; REPLICATING DNA; SOMATIC NUCLEI; FACTOR-IIIA; CHROMATIN; COMPLEX; SEQUENCES AB Nucleosomes were assembled on a plasmid carrying a Xenopus somatic 5S RNA gene prepared at different superhelix densities. The gene was preferentially assembled into a positioned nucleosome which was stable to superhelical stress. No evidence for a conformational change in the nucleosome was found, even under extreme negative superhelical stress. Transcription in an extract from Xenopus oocyte nuclei was repressed to a degree which depended on the number of nucleosomes assembled. Topoisomerase activity in the extract was effectively inhibited by camptothecin, which had no effect on transcription. Transcription of reconstitutes remained repressed relative to naked plasmids, and was independent of superhelix density. Transcripts from reconstitutes were derived solely from nucleosome-free genes. Thus, a histone octamer positioned on the gene was sufficient to block its transcription. Tryptic removal of the core histone tail domains had no effect on transcription at any superhelix density. Transcription of reconstitutes containing H3/H4 tetramers was also repressed, but not eliminated (unlike reconstitutes containing octamers), and repression was independent of superhelix density. We suggest that removal of histones H2A/H2B from the nucleosome facilitates activation of transcription in the extract. We conclude that superhelical stress alone does not activate transcription of a 5S RNA gene assembled into a nucleosome in vitro. C1 NIDDK,MOLEC BIOL LAB,ROOM 131,BLDG 6,BETHESDA,MD 20892. NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 57 TC 47 Z9 47 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 NOV PY 1991 VL 10 IS 11 BP 3419 EP 3428 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GK973 UT WOS:A1991GK97300034 PM 1717265 ER PT J AU IGNARTROWBRIDGE, DM HUGHES, AR PUTNEY, JW MCLACHLAN, JA KORACH, KS AF IGNARTROWBRIDGE, DM HUGHES, AR PUTNEY, JW MCLACHLAN, JA KORACH, KS TI DIETHYLSTILBESTROL STIMULATES PERSISTENT PHOSPHATIDYLINOSITOL LIPID TURNOVER BY AN ESTROGEN RECEPTOR-MEDIATED MECHANISM IN IMMATURE MOUSE UTERUS SO ENDOCRINOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; BREAST-CANCER-CELLS; PHOSPHOLIPASE-C; PHOSPHOINOSITIDE METABOLISM; TYROSINE PHOSPHORYLATION; INOSITOL PHOSPHATES; RAT UTERUS; 17-BETA-ESTRADIOL; MITOGENESIS; MICROINJECTION AB The effect of estrogen on phosphoinositide (PI) metabolism was evaluated in the immature mouse uterus, a tissue which undergoes estrogen-induced proliferation. Uteri isolated from untreated mice or from mice injected ip with diethylstilbestrol (DES) were incubated with [H-3]myo-inositol and assessed for incorporation of label into PI lipids or inositol phosphate generation. DES administration elicited a rapid increase in [H-3]myo-inositol incorporation, which persisted until at least 18 h post treatment. This effect could not be duplicated by incubation of uteri with DES in vitro, although [H-3]myo-inositol incorporation in uteri removed from DES-treated mice remained elevated for 3 h of in vitro incubation. Stimulation of PI lipid metabolism by DES was blocked by ICI 164,384, a specific estrogen receptor antagonist. The effect of DES on PI metabolism consisted of a time-dependent increase in the specific activity of both phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate and a significant increase of inositol (1,4,5)-trisphosphate mass by 12 h post treatment. These changes occur before the onset of estrogen-induced DNA synthesis. The results indicate that estrogens rapidly modulate PI lipid turnover through an estrogen receptor-mediated mechanism. Since the metabolic products of PI lipids are important for signal transduction and cellular proliferation, altered metabolism of these lipids may play an integral role in estrogen-induced mitogenesis. C1 NIEHS,REPROD & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 41 TC 20 Z9 20 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1991 VL 129 IS 5 BP 2423 EP 2430 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GM349 UT WOS:A1991GM34900023 PM 1935776 ER PT J AU BRANDT, DW BURTON, DW GAZDAR, AF OIE, HE DEFTOS, LJ AF BRANDT, DW BURTON, DW GAZDAR, AF OIE, HE DEFTOS, LJ TI ALL MAJOR LUNG-CANCER CELL-TYPES PRODUCE PARATHYROID HORMONE-LIKE PROTEIN - HETEROGENEITY ASSESSED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO ENDOCRINOLOGY LA English DT Article ID PEPTIDE; GENE; HYPERCALCEMIA; ENDOCRINE; TUMORS; IDENTIFICATION; PURIFICATION; CHROMOGRANIN; EXPRESSION; CARCINOMA AB We examined the production of parathyroid hormone-like protein (PLP) by all major lung cancer cell types, including epidermoid, small cell, and adenocarcinoma. We demonstrated that cell lines derived from each cell type released PLP into culture medium. To determine the predominant species of PLP produced by the cell lines, guanidine hydrochloride extracts were prepared and analyzed for PLP by high performance size exclusion chromatography under denaturing conditions. Cell lines from each of the major lung tumors produced multiple and different forms of PLP. The estimated molecular sizes of the PLP species ranged from 3.5-11.7 kilodaltons. Our results demonstrate that PLP is produced by all major lung cancer cell types and extend these observations to adenocarcinoma and large cell carcinomas of the lung. Furthermore, we observed PLP heterogeneity among these different cell types, which may represent tissue-specific PLP processing among different human lung tumors. C1 UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. VET ADM MED CTR,SAN DIEGO,CA 92161. NIH,USN,MED ONCOL BRANCH,BETHESDA,MD 20814. NR 27 TC 64 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1991 VL 129 IS 5 BP 2466 EP 2470 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GM349 UT WOS:A1991GM34900029 PM 1935781 ER PT J AU WEBSTER, EL TRACEY, DE DESOUZA, EB AF WEBSTER, EL TRACEY, DE DESOUZA, EB TI UP-REGULATION OF INTERLEUKIN-1 RECEPTORS IN MOUSE ATT-20 PITUITARY-TUMOR CELLS FOLLOWING TREATMENT WITH CORTICOTROPIN-RELEASING FACTOR SO ENDOCRINOLOGY LA English DT Note ID LINE ATT-20; ADRENALECTOMY; SECRETION; RESPONSES; ANTERIOR AB Treatment of AtT-20 cell cultures with increasing concentrations of rat/human corticotropin-releasing factor (r/hCRF) for 24 h resulted in a dose-dependent 2-3 fold increase in specific I-125-labelled recombinant human IL-1-alpha (I-125-IL-1-alpha) binding that was paralleled by a 70 - 80% decrease in I-125-Tyr(o)-ovine CRF binding. Saturation analysis of I-125-IL-1-alpha binding in control and CRF-treated cultures indicated that CRF produced an increase in the density (B(max)) of IL-1 receptors without altering their affinity (K(D)). The CRF-induced upregulation of IL-1 receptors appears to be mediated through specific membrane receptors for CRF since the CRF receptor antagonist, alpha-helical oCRF (9-41), blocked the CRF-induced upregulation of IL-1 receptors without producing any effect on I-125-IL-1-alpha binding by itself. In summary, these data demonstrate complex interactions between CRF and IL-1 at the pituitary level and identify potential novel mechanisms for cytokines to alter neuroendocrine function. C1 UPJOHN CO,HYPERSENSIT DIS RES,KALAMAZOO,MI 49007. RP WEBSTER, EL (reprint author), NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD 21224, USA. NR 15 TC 53 Z9 53 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1991 VL 129 IS 5 BP 2796 EP 2798 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GM349 UT WOS:A1991GM34900076 PM 1834455 ER PT J AU SUSIC, V REITH, MEA ZLOKOVIC, BV LAJTHA, A JACOBSON, AE RICE, KC LIPOVAC, MN AF SUSIC, V REITH, MEA ZLOKOVIC, BV LAJTHA, A JACOBSON, AE RICE, KC LIPOVAC, MN TI ELECTROENCEPHALOGRAPHIC CHARACTERISTICS OF AUDIOGENIC-SEIZURES INDUCED IN METAPHIT-TREATED SMALL RODENTS SO EPILEPSIA LA English DT Article DE CONVULSIONS; NEUROLOGIC MODELS; METAPHIT; AUDIOGENIC SEIZURES; PHENCYCLIDINE; N-METHYL-D-ASPARTATE ID PHENCYCLIDINE-LIKE DRUGS; MERIONES-UNGUICULATUS; MICE; RECEPTORS; LIGAND; GERBIL; RATS; PCP AB Adult male mice, rats, and guinea pigs were subjected to intense sound stimulation of an electric bell (100 dB, 12 kHz for 60 s) after a single intraperitoneal (i.p.) injection of metaphit (1-(1-(3 isothiocyanatophenyl)cyclohexyl) piperidine) (50 mg/kg). When the animals were tested 24 h after administration of metaphit, audiogenic seizures were observed. None of the control saline-injected animals had convulsions. EEG recordings demonstrated the appearance of paroxysmal activity and spike-wave complexes in the trace from cortical and hippocampal electrodes, with frequency and amplitude increasing with time. Behaviorally, myoclonic jerks of facial muscles, ears, and neck appeared, but no correlation was noted between EEG and the motor phenomena. Auditory stimulation was necessary to elicit the full-blown sequence of seizure responses consisting of wild running followed by clonic and then tonic extension. At the time of seizures, repetitive high-amplitude spikes and waves appeared in the EEG, followed by profound EEG and behavioral depression. None of the animals died during or immediately after seizures. The seizure response to sound stimulation of mice, rats, and guinea pigs was phenomenologically similar, with minor differences in quantitative pattern of convulsive components, which suggests that all three animal species share the common property of extreme susceptibility to audiogenic stimulation caused by metaphit administration. C1 NATHAN S KLINE INST PSYCHIAT RES,CTR NEUROCHEM,NEW YORK,NY. NIDDKD,NEUROSCI LAB,BETHESDA,MD. RP SUSIC, V (reprint author), UNIV BELGRADE,FAC MED,INST MED PHYSIOL,POB 783,BELGRADE,YUGOSLAVIA. NR 20 TC 24 Z9 25 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 NOV-DEC PY 1991 VL 32 IS 6 BP 783 EP 790 DI 10.1111/j.1528-1157.1991.tb05534.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA GU517 UT WOS:A1991GU51700006 PM 1743149 ER PT J AU MARASTONI, M TOMATIS, R BALBONI, G SALVADORI, S LAZARUS, LH AF MARASTONI, M TOMATIS, R BALBONI, G SALVADORI, S LAZARUS, LH TI ON THE DEGRADATION OF THE DELTORPHIN PEPTIDES BY PLASMA AND BRAIN HOMOGENATE SO FARMACO LA English DT Article ID DELTA-OPIOID RECEPTORS; SOLID-PHASE SYNTHESIS; HIGH-AFFINITY; SKIN PEPTIDE; SELECTIVITY; DERMORPHIN; DERMENKEPHALIN; FRAGMENTS; AGONIST; RESIN AB The peptidase-resistance of deltorphins (DEL-A, H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) and (DEL-C, H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2), highly selective and potent agonists of the delta opioid receptor, were investigated in vitro. DEL-C was fully resistant to degradation by rat plasma and strongly resistant to degradation by rat brain homogenates. DEL-A was cleaved with a half-life of 131.6 min upon incubation with plasma, and 57.4 min with rat brain homogenates. N-terminal truncated sequences of DEL-A and -C with free carboxyl groups, were also analyzed for receptor binding activity using [H-3] DADLE for delta sites and [H-3] DAGO for mu sites. The high enzymatic stability associated with deltorphins and their degradation products may make them prime candidates to characterize the role of delta-receptors in vivo. C1 UNIV FERRARA,DEPT PHARMACEUT SCI,VIA SCANDIANA 21,I-44100 FERRARA,ITALY. NIEHS,PEPTIDE NEUROCHEM LMIN,RES TRIANGLE PK,NC 27709. OI SALVADORI, Severo/0000-0002-8224-2358 NR 16 TC 18 Z9 18 U1 0 U2 1 PU SOC CHIMICA ITALIANA PI ROME PA VIALE LIEGI 48, I-00198 ROME, ITALY SN 0014-827X J9 FARMACO JI Farmaco PD NOV PY 1991 VL 46 IS 11 BP 1273 EP 1279 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GY073 UT WOS:A1991GY07300003 PM 1667359 ER PT J AU HEARING, VJ TSUKAMOTO, K AF HEARING, VJ TSUKAMOTO, K TI ENZYMATIC CONTROL OF PIGMENTATION IN MAMMALS SO FASEB JOURNAL LA English DT Review DE MELANIN; PIGMENTATION; MELANOGENESIS ID MELANOCYTE-STIMULATING HORMONE; HAIR FOLLICULAR MELANOCYTES; TYROSINASE-RELATED PROTEIN; IA OCULOCUTANEOUS ALBINISM; CULTURED HUMAN MELANOCYTES; ENCODING MOUSE TYROSINASE; MESSENGER-RNA LEVELS; MOLECULAR-BASIS; DOPACHROME OXIDOREDUCTASE; METAL-IONS AB Visible pigmentation in mammals results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. The melanins are produced in melanocytes and can be of two basic types: eumelanins, which are brown or black, and phaeomelanins, which are red or yellow. In mammals typically there are mixtures of both types. The most essential enzyme in this melanin biosynthetic pathway is tyrosinase and it is the only enzyme absolutely required for melanin production. However, recent studies have shown that mammalian melanogenesis is not regulated solely by tyrosinase at the enzymatic level, and have identified additional melanogenic factors that can modulate pigmentation in either a positive or negative fashion. In addition, other pigment-specific genes that are related to tyrosinase have been cloned which encode proteins that apparently work together at the catalytic level to specify the quantity and quality of the melanins synthesized. Future research should provide a greater understanding of the enzymatic interactions, processing, and tissue specificity that are important to pigmentation in mammals. C1 YAMANASHI MED COLL,DEPT DERMATOL,YAMANASHI 40938,JAPAN. RP HEARING, VJ (reprint author), NCI,CELL BIOL LAB,ROOM 1B22,BETHESDA,MD 20892, USA. NR 100 TC 568 Z9 577 U1 7 U2 47 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1991 VL 5 IS 14 BP 2902 EP 2909 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GP269 UT WOS:A1991GP26900004 PM 1752358 ER PT J AU DE LUCA, LM AF DE LUCA, LM TI RETINOIDS AND THEIR RECEPTORS IN DIFFERENTIATION, EMBRYOGENESIS, AND NEOPLASIA SO FASEB JOURNAL LA English DT Review DE DIFFERENTIATION; EMBRYOGENESIS; NEOPLASIA; VAGINAL EPITHELIUM; RETINOIC ACID RECEPTORS; RESPONSE ELEMENT; LEUKEMIA; CHROMOSOMAL TRANSLOCATION ID EMBRYONAL CARCINOMA-CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; ACID-RESPONSIVE ELEMENT; MOUSE TERATOCARCINOMA CELLS; THYROID-HORMONE RECEPTORS; TARGET GENE SPECIFICITY; HUMAN OSTEOCALCIN GENE; DIBUTYRYL-CYCLIC-AMP; V-ERB-A; VITAMIN-A AB The crucial role of retinoids in controlling differentiation processes has become evident from studies conducted in a variety of in vivo and in vitro systems. Most striking is the role of retinoic acid as a morphogenic substance in vertebrate limb development, but equally important is its role in the maintenance of epithelial integrity in most superficial linings of the body. The similarity of the mode of action of retinoids to that of the steroid and thyroid hormones has recently been demonstrated with the discovery of the nuclear receptors for retinoic acid, which belong to the steroid/thyroid hormone receptor superfamily. These receptors act as transcriptional activators by binding as heterodimers to specific nucleotide sequences in the response elements of target genes. Response elements for retinoic acid have so far been identified for the rat growth hormone and phosphoenolpyruvate carboxykinase, the mouse complement H and laminin B1, the human and mouse retinoic acid receptor beta, the human osteocalcin, and the human alcohol dehydrogenase genes. The retinoic acid response element (RARE) for the rat growth hormone gene is also a thyroid hormone response element (TRE), and the AP-1 binding site of the human osteocalcin promoter is also a vitamin D response element (VDRE) and a RARE. Both these elements are palindromic. Other RAREs have a direct repeat configuration of the half-site motif AGGTCA separated by five nucleotides (AGGTCA xxxxx AGGTCA). The direct repeat arrangement of the same core motif AGGTCA separated by three or four nucleotides becomes a VDRE or TRE, respectively. A point mutation has been identified in the RAR-alpha-gene of embryonal carcinoma cells resistant to retinoic acid. In addition to the three retinoic acid receptors (alpha, beta, gamma) belonging to the steroid/thyroid hormone receptor superfamily, a second class of retinoid receptors (RXR) alpha, beta, gamma has also been characterized and its relatedness to a gene, XR2C, of the locus ultraspiracle required for pattern formation in Drosophila has been established. That would suggest that both vertebrates and invertebrates may require similar transcriptional activators during morphogenesis. An RXRE has been identified in the CRBPII gene promoter and it contains five repeats of the canonical sequence AGGTCA separated by one nucleotide. The importance of retinoids, both as chemopreventive agents of tumorigenesis and potent differentiation inducers of neoplastic cells, can only be emphasized by the recent finding that the t (15;17) (q21- q11-22) translocation, specifically associated with acute promyelocytic leukemia, also causes translocation of the retinoic acid receptor alpha-gene and its fusion with with a new locus, myl, of unknown function. Although the biological consequences of this translocation are unknown, the finding supports the concept that retinoids and their receptors are directly involved in neoplasia. RP DE LUCA, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BLDG 37, ROOM 3A-17, BETHESDA, MD 20892 USA. NR 102 TC 820 Z9 828 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1991 VL 5 IS 14 BP 2924 EP 2933 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GP269 UT WOS:A1991GP26900007 PM 1661245 ER PT J AU MERLINO, GT AF MERLINO, GT TI TRANSGENIC ANIMALS IN BIOMEDICAL-RESEARCH SO FASEB JOURNAL LA English DT Article DE GENE REGULATION; GENE THERAPY; CANCER; MUTATION; BIOTECHNOLOGY; TARGETED GENE INACTIVATION ID TGF-ALPHA; INT-1 PROTOONCOGENE; LIVER NEOPLASIA; GERM LINE; T-CELLS; MICE; GENE; MOUSE; EXPRESSION; DEFICIENT AB The advent of transgenic technology, in which foreign genetic information is stably introduced into the mammalian germ line, has dramatically enhanced our basic knowledge of physiologic and pathologic processes. Transgenic animals created by these genetic manipulations are being used to provide insights into gene regulation, development, pathogenesis, and the treatment of disease. Furthermore, transgenic biotechnology holds great promise for the creation of genetically superior livestock and the industrial production of precious pharmaceuticals. It is evident now that the study and use of transgenic animals will significantly improve the human condition. RP MERLINO, GT (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 27 Z9 27 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1991 VL 5 IS 14 BP 2996 EP 3001 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GP269 UT WOS:A1991GP26900017 PM 1752364 ER PT J AU HEYES, MP AF HEYES, MP TI RELATIONSHIP BETWEEN INTERFERON-GAMMA, INDOLEAMINE-2,3-DIOXYGENASE AND TRYPTOPHAN SO FASEB JOURNAL LA English DT Letter ID QUINOLINIC ACID; KYNURENIC ACID; METABOLITE; BRAIN RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1991 VL 5 IS 14 BP 3003 EP 3004 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GP269 UT WOS:A1991GP26900019 PM 1752366 ER PT J AU KIMZEY, LM GUMOWSKI, J MERRIAM, GR GRIMES, GJ NELSON, LM AF KIMZEY, LM GUMOWSKI, J MERRIAM, GR GRIMES, GJ NELSON, LM TI ABSORPTION OF MICRONIZED PROGESTERONE FROM A NONLIQUEFYING VAGINAL CREAM SO FERTILITY AND STERILITY LA English DT Note ID PLASMA C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,PHARMACEUT DEV SERV SECT,BETHESDA,MD 20892. NR 4 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 1991 VL 56 IS 5 BP 995 EP 996 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA GN926 UT WOS:A1991GN92600034 PM 1936339 ER PT J AU SANDERS, VM FUCHS, BA PRUETT, SB KERKVLIET, NI KAMINSKI, NE AF SANDERS, VM FUCHS, BA PRUETT, SB KERKVLIET, NI KAMINSKI, NE TI SYMPOSIUM ON INDIRECT MECHANISMS OF IMMUNE MODULATION SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Review C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. MISSISSIPPI STATE UNIV,MISSISSIPPI STATE,MS 39762. OREGON STATE UNIV,CORVALLIS,OR 97331. RP SANDERS, VM (reprint author), NIEHS,MAIL DROP C1-04,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1991 VL 17 IS 4 BP 641 EP 650 DI 10.1016/0272-0590(91)90174-3 PG 10 WC Toxicology SC Toxicology GA GN917 UT WOS:A1991GN91700001 PM 1685714 ER PT J AU GOODMAN, JI WARD, JM POPP, JA KLAUNIG, JE FOX, TR AF GOODMAN, JI WARD, JM POPP, JA KLAUNIG, JE FOX, TR TI MOUSE-LIVER CARCINOGENESIS - MECHANISMS AND RELEVANCE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID B6C3F1 MOUSE; HA-RAS; HEPATOCELLULAR-CARCINOMA; CHEMICAL CARCINOGENS; ACTIVATED ONCOGENES; CELL-PROLIFERATION; EPITHELIAL-CELLS; ALBUMIN GENE; TUMORS; METHYLATION C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46223. RP GOODMAN, JI (reprint author), MICHIGAN STATE UNIV,INST ENVIRONM TOXICOL,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824, USA. FU NIEHS NIH HHS [ES-05299] NR 72 TC 62 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1991 VL 17 IS 4 BP 651 EP 665 DI 10.1016/0272-0590(91)90175-4 PG 15 WC Toxicology SC Toxicology GA GN917 UT WOS:A1991GN91700002 PM 1685715 ER PT J AU HOOFNAGLE, JH BERGASA, NV AF HOOFNAGLE, JH BERGASA, NV TI METHOTREXATE THERAPY OF PRIMARY BILIARY-CIRRHOSIS - PROMISING BUT WORRISOME SO GASTROENTEROLOGY LA English DT Editorial Material ID CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; COLCHICINE; HEPATOTOXICITY; CYCLOSPORINE C1 NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. RP HOOFNAGLE, JH (reprint author), NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 20 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1991 VL 101 IS 5 BP 1440 EP 1442 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GM008 UT WOS:A1991GM00800039 PM 1936816 ER PT J AU MITNICK, LL AF MITNICK, LL TI HEALTH AND BEHAVIOR PROGRAMS AT NIMH SO GENERAL HOSPITAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,DIV BASIC BRAIN & BEHAV SCI,BASIC PREVENT & BEHAV MED RES BRANCH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1991 VL 13 IS 6 BP 362 EP 363 DI 10.1016/0163-8343(91)90059-6 PG 2 WC Psychiatry SC Psychiatry GA GQ996 UT WOS:A1991GQ99600007 ER PT J AU LE, SY SHAPIRO, BA CHEN, JH NUSSINOV, R MAIZEL, JV AF LE, SY SHAPIRO, BA CHEN, JH NUSSINOV, R MAIZEL, JV TI RNA PSEUDOKNOTS DOWNSTREAM OF THE FRAMESHIFT SITES OF RETROVIRUSES SO GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING LA English DT Article ID MOSAIC-VIRUS RNA; COMPLETE NUCLEOTIDE-SEQUENCE; BOVINE LEUKEMIA-VIRUS; MAMMARY-TUMOR VIRUS; ROUS-SARCOMA VIRUS; MESSENGER-RNA; SECONDARY STRUCTURE; IMMUNODEFICIENCY VIRUSES; STATISTICAL SIGNIFICANCE; DROSOPHILA-MELANOGASTER AB RNA pseudoknot structural motifs could have implications for a wide range of biological processes of RNAs. In this study, the potential RNA pseudoknots just down-stream from the known and suspected retroviral frame-shift sites were predicted in the Rous sarcoma virus, primate immunodeficiency viruses (HIV-1, HIV-2, and SIV), equine infectious anemia virus, visna virus, bovine leukemia virus, human T-cell leukemia virus (types I and II), mouse mammary tumor virus, Mason-Pfizer monkey virus, and simian SRV-1 type-D retrovirus. Also, the putative RNA pseudoknots were detected in the gag-pol overlaps of two retrotransposons of Drosophila, 17.6 and gypsy, and the mouse intracisternal A particle. For each sequence, the thermodynamic stability and statistical significance of the secondary structure involved in the predicted tertiary structure were assessed and compared. Our results show that the stem-loop structures in the pseudoknots are both thermodynamically highly stable and statistically significant relative to other such configurations that potentially occur in the gag-pol or gag-pro and pro-pol junction domains of these viruses (300 nucleotides upstream and downstream from the possible frameshift sites are included). Moreover, the structural features of the predicted pseudoknots following the frameshift site of pro-pol overlaps of the HTLV-1 and HTLV-2 retroviruses are structurally well conserved. The occurrence of eight compensatory base changes in the tertiary interaction of the two related sequences allow the conservation of their tertiary structures in spite of the sequence divergence. The results support the possible control mechanism for frameshifting proposed by Brierley et al. [1] and Jacks et al. [2, 3]. C1 NCI,DIV CANC BIOL DIAGNOSIS & CTR,MATH BIOL LAB,POB B,ROOM 151,FREDERICK,MD 21701. NCI,PROGRAM RESOURCES INC,ADV SCI COMP LAB,FREDERICK,MD 21701. NATL RES COUNCIL CANADA,INST BIOL SCI,OTTAWA K1A 0R6,ONTARIO,CANADA. NR 51 TC 28 Z9 30 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1050-3862 J9 GENET ANAL-BIOMOL E JI Genet. Anal.-Biomol. Eng. PD NOV PY 1991 VL 8 IS 7 BP 191 EP 205 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA GX102 UT WOS:A1991GX10200001 PM 1663382 ER PT J AU ABBOTT, MK LENGYEL, JA AF ABBOTT, MK LENGYEL, JA TI EMBRYONIC HEAD INVOLUTION AND ROTATION OF MALE TERMINALIA REQUIRE THE DROSOPHILA LOCUS HEAD INVOLUTION DEFECTIVE SO GENETICS LA English DT Article ID MELANOGASTER; EXPRESSION; GENETICS; COMPLEX; GENES AB We have characterized the head involution defective (hid) locus which is located within the chromosomal region 75B8-C1,2. During the morphogenetic reorganization of the embryonic head region, hid+ function is necessary for the movement of the dorsal fold across the procephalon and clypeolabrum, a process that forms the frontal sac. The absence of the frontal sac in the hid mutant embryos affects the formation of the dorsal bridge and disrupts the development of the larval cephalopharyn-geal skeleton. In addition to its embryonic role, this same hid function is also required during pupal development for the 360-degrees ratation of the male terminalia about the anterior-posterior body axis, and for a late step of wing blade morphogenesis. Although the abnormal wing phenotype caused by the Wrinkled (W) mutation is quite different from the one resulting from the loss-of-function hid mutations, the characterization of EMS-induced W revertants reveals that W is actually an antimorphic allele of hid. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. FU NICHD NIH HHS [HD09948]; NIGMS NIH HHS [GM10052] NR 26 TC 77 Z9 78 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 1991 VL 129 IS 3 BP 783 EP 789 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA GL996 UT WOS:A1991GL99600020 PM 1752422 ER PT J AU VANDERHOUT, AH VANDERVLIES, P WIJMENGA, C LI, FP OOSTERHUIS, JW BUYS, CHCM AF VANDERHOUT, AH VANDERVLIES, P WIJMENGA, C LI, FP OOSTERHUIS, JW BUYS, CHCM TI THE REGION OF COMMON ALLELIC LOSSES IN SPORADIC RENAL-CELL CARCINOMA IS BORDERED BY THE LOCI-D3S2 AND THRB SO GENOMICS LA English DT Article ID VONHIPPEL-LINDAU DISEASE; SHORT ARM; LUNG-CANCER; MOLECULAR ANALYSIS; TUMOR-CELLS; CHROMOSOME-3; DELETION; HETEROZYGOSITY; 3P; ADENOCARCINOMA C1 NCI,BOSTON,MA. RP VANDERHOUT, AH (reprint author), UNIV GRONINGEN,DEPT MED GENET,A DEUSINGLAAN 4,9713 AW GRONINGEN,NETHERLANDS. RI Wijmenga, Cisca/D-2173-2009; OI Wijmenga, Cisca/0000-0002-5635-1614 NR 34 TC 45 Z9 45 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 537 EP 542 DI 10.1016/0888-7543(91)90060-R PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600005 PM 1685475 ER PT J AU LAWLER, J DUQUETTE, M FERRO, P COPELAND, NG GILBERT, DJ JENKINS, NA AF LAWLER, J DUQUETTE, M FERRO, P COPELAND, NG GILBERT, DJ JENKINS, NA TI CHARACTERIZATION OF THE MURINE THROMBOSPONDIN GENE SO GENOMICS LA English DT Article ID TRANSCRIPTION FACTOR; EXTRACELLULAR-MATRIX; PROMOTER REGION; MOUSE CHROMOSOME-2; PROTO-ONCOGENE; DNA-SEQUENCES; BINDING-SITE; 1ST INTRON; CYCLIC-AMP; PROTEINS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP LAWLER, J (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115, USA. FU NCI NIH HHS [N01-CO-74101]; NHLBI NIH HHS [HL-28749, HL-42443] NR 48 TC 36 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 587 EP 600 DI 10.1016/0888-7543(91)90066-N PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600011 PM 1774063 ER PT J AU YELICK, PC KOZAK, C KWON, YK SELDIN, MF HECHT, NB AF YELICK, PC KOZAK, C KWON, YK SELDIN, MF HECHT, NB TI THE MOUSE TRANSITION PROTEIN-1 GENE CONTAINS A B1 REPETITIVE ELEMENT AND IS LOCATED ON CHROMOSOME-1 SO GENOMICS LA English DT Article ID CONSERVED LINKAGE GROUP; NUCLEOTIDE-SEQUENCE; CDNA CLONE; MAMMALIAN SPERMATIDS; MESSENGER-RNA; DNA; LOCALIZATION; TP1; SPERMATOGENESIS; IDENTIFICATION C1 TUFTS UNIV,DEPT BIOL,MEDFORD,MA 02115. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. FU NHGRI NIH HHS [HG 00101]; NIGMS NIH HHS [GM 29224] NR 36 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 687 EP 694 DI 10.1016/0888-7543(91)90076-Q PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600021 PM 1685480 ER PT J AU WEBER, JL POLYMEROPOULOS, MH MAY, PE KWITEK, AE XIAO, H MCPHERSON, JD WASMUTH, JJ AF WEBER, JL POLYMEROPOULOS, MH MAY, PE KWITEK, AE XIAO, H MCPHERSON, JD WASMUTH, JJ TI MAPPING OF HUMAN CHROMOSOME-5 MICROSATELLITE DNA POLYMORPHISMS SO GENOMICS LA English DT Article ID HUMAN-GENE; REGION; LOCALIZATION; LINKAGE; LOCI; ASSIGNMENT; ORDER C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,IRVINE,CA 92717. RP WEBER, JL (reprint author), MARSHFIELD MED RES FDN,1000 N OAK AVE,MARSHFIELD,WI 54449, USA. FU NHGRI NIH HHS [HG-00248, HG-00320]; NICHD NIH HHS [HD-18642] NR 27 TC 92 Z9 92 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 695 EP 700 DI 10.1016/0888-7543(91)90077-R PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600022 PM 1774070 ER PT J AU POLYMEROPOULOS, MH XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H MERRIL, CR TI THE HUMAN D5-DOPAMINE RECEPTOR (DRD5) MAPS ON CHROMOSOME-4 SO GENOMICS LA English DT Note ID REGION; GENE RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032, USA. NR 7 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 777 EP 778 DI 10.1016/0888-7543(91)90091-R PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600036 PM 1774076 ER PT J AU WHITE, MB LEPPERT, M NIELSEN, D ZIELENSKI, J GERRARD, B STEWART, C DEAN, M AF WHITE, MB LEPPERT, M NIELSEN, D ZIELENSKI, J GERRARD, B STEWART, C DEAN, M TI A DENOVO CYSTIC-FIBROSIS MUTATION - CGA (ARG) TO TGA (STOP) AT CODON-851 OF THE CFTR GENE SO GENOMICS LA English DT Note ID DNA; IDENTIFICATION C1 UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84132. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP WHITE, MB (reprint author), FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU PHS HHS [N01-C0-74102] NR 10 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1991 VL 11 IS 3 BP 778 EP 779 DI 10.1016/0888-7543(91)90092-S PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GK046 UT WOS:A1991GK04600037 PM 1723056 ER PT J AU KHACHATURIAN, ZS AF KHACHATURIAN, ZS TI CALCIUM AND THE AGING BRAIN - UPSETTING A DELICATE BALANCE SO GERIATRICS LA English DT Article RP KHACHATURIAN, ZS (reprint author), NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 13 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 NOV PY 1991 VL 46 IS 11 BP 78 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA GP543 UT WOS:A1991GP54300007 PM 1657728 ER PT J AU INSKIP, PD WANG, ZY FEN, YS AF INSKIP, PD WANG, ZY FEN, YS TI SUITABILITY OF CHINESE OIL-WELL LOGGERS FOR AN EPIDEMIOLOGIC-STUDY OF THE CARCINOGENIC EFFECTS OF NEUTRONS SO HEALTH PHYSICS LA English DT Note ID BOMB SURVIVORS; DOSIMETRY; CANCER; MORTALITY; RISK AB Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% < 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation. C1 MINIST PUBL HLTH, IND HYG LAB, BEIJING, PEOPLES R CHINA. RP INSKIP, PD (reprint author), NCI, RADIAT EPIDEMIOL BRANCH, EXECUT PLAZA N ROOM 408, BETHESDA, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 1991 VL 61 IS 5 BP 637 EP 640 DI 10.1097/00004032-199111000-00007 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA GL720 UT WOS:A1991GL72000007 PM 1752747 ER PT J AU RANDOLPH, FL RIDGWAY, P CARLING, PJ AF RANDOLPH, FL RIDGWAY, P CARLING, PJ TI RESIDENTIAL PROGRAMS FOR PERSONS WITH SEVERE MENTAL-ILLNESS - A NATIONWIDE SURVEY OF STATE-AFFILIATED AGENCIES SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID CARE AB About 1,500 agencies responded to a nationwide survey of community residential programs affiliated with state departments of mental health that was conducted in 1986-87. The agencies served more than 59,000 individuals who had psychiatric disabilities in more than 16,000 residential settings. The results reveal rapid growth in the number of programs since 1980 and the availability of a broad range of residential programs. Group homes and supervised apartments were the most common types of residential programs identified in the survey. The most commonly offered services were social and recreational activities, medication supervision, and on-site crisis intervention. Programs also offered such services as client advocacy and case management. Most program staff did not have professional training in a mental health field. C1 UNIV VERMONT,CTR COMMUNITY CHANGE HOUSING & SUPPORT,BURLINGTON,VT 05405. BOSTON UNIV,CTR PSYCHIAT REHABIL,COMMUNITY RESIDENTIAL REHABIL PROJECT,BOSTON,MA 02215. RP RANDOLPH, FL (reprint author), NIMH,5600 FISHERS LANE,ROOM 11C-22,ROCKVILLE,MD 20857, USA. FU PHS HHS [G008435030] NR 22 TC 34 Z9 34 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD NOV PY 1991 VL 42 IS 11 BP 1111 EP 1115 PG 5 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA GM535 UT WOS:A1991GM53500006 PM 1743637 ER PT J AU MAEKAWA, M SUDO, K LI, SSL KANNO, T AF MAEKAWA, M SUDO, K LI, SSL KANNO, T TI GENOTYPIC ANALYSIS OF FAMILIES WITH LACTATE-DEHYDROGENASE A(M) DEFICIENCY BY SELECTIVE DNA AMPLIFICATION SO HUMAN GENETICS LA English DT Article ID M-SUBUNIT; GENE; GENERATION; POLYMERASE AB Genomic DNA prepared from LDH-A-deficient whole blood was amplified by the polymerase chain reaction technique using two primers specific for the active human LDH-A gene. The amplified fragment was examined by direct agarose gel electrophoresis, and a deletion of 20 base pairs (bp) in exon 6 of the LDH-A gene was found. The results permitted a clear distinction between the homozygous mutant, the heterozygous mutant, and wild-type genotypes. Moreover, HinfI digestion and direct sequencing of the amplified product confirmed the results from direct agarose gel electrophoresis. Four families, including 18 individuals, were shown to contain the same mutation, that is a 20-bp deletion in exon 6. All genotypes were consistent with their biochemical phenotypes as evaluated by the ratio of LDH-B to LDH-A subunits in erythrocytes. Thus, all four known affected families in Japan have been shown to carry the same mutant gene, which may have been derived from a single mutational event. C1 JIKEI UNIV, DEPT LAB MED, MINATO KU, TOKYO 105, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP MAEKAWA, M (reprint author), HAMAMATSU UNIV SCH MED, DEPT LAB MED, HANDA CHO 3600, HAMAMATSU, SHIZUOKA 431-31, JAPAN. NR 14 TC 11 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1991 VL 88 IS 1 BP 34 EP 38 DI 10.1007/BF00204925 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA GR278 UT WOS:A1991GR27800005 PM 1959923 ER PT J AU MEDEIROS, LJ PEIPER, SC ELWOOD, L YANO, T RAFFELD, M JAFFE, ES AF MEDEIROS, LJ PEIPER, SC ELWOOD, L YANO, T RAFFELD, M JAFFE, ES TI ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS - A MOLECULAR ANALYSIS OF 8 CASES SO HUMAN PATHOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; LETHAL MIDLINE GRANULOMA; T-CELL LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; RENAL-TRANSPLANT RECIPIENT; POLYMERASE CHAIN-REACTION; POLYMORPHIC RETICULOSIS; DNA; PROLIFERATION; NEOPLASMS C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL. RP MEDEIROS, LJ (reprint author), NCI,HEMATOPATHOL SECT,PATHOL LAB,BLDG 10,ROOM 2N108,BETHESDA,MD 20892, USA. NR 43 TC 134 Z9 136 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1991 VL 22 IS 11 BP 1150 EP 1157 PG 8 WC Pathology SC Pathology GA GT371 UT WOS:A1991GT37100013 PM 1743700 ER PT J AU GILL, JR GROSSMAN, E GOLDSTEIN, DS AF GILL, JR GROSSMAN, E GOLDSTEIN, DS TI HIGH URINARY DOPA AND LOW URINARY DOPAMINE-TO-DOPA RATIO IN SALT-SENSITIVE HYPERTENSION SO HYPERTENSION LA English DT Article DE DOPAMINE; SALT; SODIUM; NOREPINEPHRINE; SALT-SENSITIVE HYPERTENSION; DOPA ID SODIUM-INTAKE; DIETARY SALT; ADRENERGIC ACTIVITY; PLASMA; NOREPINEPHRINE; EXCRETION; BLOOD; CATECHOLAMINES; INHIBITION; RESPONSES AB Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for-7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p < 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake. Among individual patients, cumulative sodium retention during the first 3 days of salt loading was unrelated to the magnitude of the pressor response; however, the dopa excretion rate was positively correlated with the magnitude of the pressor response (r = 0.62, p = 0.015). The results suggest that salt-sensitive patients have decreased renal uptake or decarboxylation of dopa and that this deficiency is associated with enhanced delivery of dopa to renal uptake sites during dietary salt loading. A high rate of urinary excretion of dopa and a low urinary dopamine/dopa ratio appear to be markers of salt-sensitive hypertension in humans. RP GILL, JR (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,BETHESDA,MD 20892, USA. NR 31 TC 59 Z9 60 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 NOV PY 1991 VL 18 IS 5 BP 614 EP 621 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GN922 UT WOS:A1991GN92200007 PM 1937664 ER PT J AU JESSOP, JJ TAPLITS, MS AF JESSOP, JJ TAPLITS, MS TI EFFECT OF HIGH-DOSES OF MORPHINE ON CON-A INDUCED LYMPHOKINE PRODUCTION INVITRO SO IMMUNOPHARMACOLOGY LA English DT Article DE MORPHINE; LYMPHOKINE PRODUCTION; OPIATE; IMMUNE FUNCTION ID HUMAN-BLOOD LYMPHOCYTES; OPIOID-PEPTIDES; BETA-ENDORPHIN; PERIPHERAL-BLOOD; OPIATE RECEPTORS; STRESS; INVOLVEMENT; LEUKOCYTES; RESPONSES; TRANSPORT AB Morphine, a potent analgesic drug as well as the active metabolite derived from heroin, has been reported to affect a variety of immune functions. In vivo administration of high doses of morphine to animals has been shown to inhibit natural killer (NK) cell activity in the rat (Shavit et al., 1984) and splenic T cell mitogenic response in the mouse (Bryant et al., 1988). We report here on the effect of morphine sulfate (MS) (0.2-1.6 mM) on Concanavalin-A (Con-A) stimulated lymphokine production by mouse splenocytes in vitro. Twenty-four hour incubation of mouse splenocytes with MS, removal of the drug and activation with Con-A resulted in a significant (linear regression, P < 0.001) dose-related inhibition of lymphokine production (IC50 = 0.8 mM) as measured by bioassay for interleukin-2 (IL-2)/interleukin-4 (IL-4). The inhibitory effect of MS on lymphokine production was not blocked by opiate antagonists nor was the inhibitory effect mimicked by equivalent concentrations of mu, delta or epsilon receptor-specific opiate agonists. Exposure to the concentrations of MS used did not reduce viability of mouse splenocytes as determined by Trypan Blue exclusion. Morphine did not inhibit protein synthesis or adenylate cyclase activity in a T cell clone under identical conditions, indicating that MS, in this concentration range, does not simply interfere with all cell functions in a nonspecific manner. These results suggest that (1) morphine directly inhibits splenocyte function, (2) the inhibitory effect is not mediated through classical opiate receptors, and (3) the inhibitory effect is not due to toxicity. RP JESSOP, JJ (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 28 TC 34 Z9 36 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD NOV-DEC PY 1991 VL 22 IS 3 BP 175 EP 184 DI 10.1016/0162-3109(91)90042-W PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA GV111 UT WOS:A1991GV11100004 PM 1663496 ER PT J AU GOTTSTEIN, B STOCKS, NI SHEARER, GM NASH, TE AF GOTTSTEIN, B STOCKS, NI SHEARER, GM NASH, TE TI HUMAN CELLULAR IMMUNE-RESPONSE TO GIARDIA-LAMBLIA SO INFECTION LA English DT Article ID EXPERIMENTAL HUMAN INFECTIONS; ANTIGENIC VARIATION; ANTIBODY; INVITRO; MURIS; MICE AB Human peripheral blood mononuclear cells (PBMC) from two individuals experimentally and one naturally infected with Giardia lamblia responded strongly (in an in vitro lymphocyte proliferation assay) to both heterologous and homologous (parasite origin) G. lamblia antigen stimuli. Proliferative responses to specific antigens as determined by T-cell blotting were due to Giardia T-cell epitopes mostly present in antigens lower than M(r) 85,000 and 31,000 in isolates PM and GS/M-H7, respectively. Additionally, Il-2 production of PBMC respective to T lymphocyte subsets under antigen stimulation were determined in one selected patient. Proliferative. and lymphokine responses could be associated with CD4+ PBMC depleted of CD8+ T cells and not with PBMC depleted of CD4+ T cells. These preliminary results suggest the initiation of larger studies addressing questions of cell-mediated immune response and the role of lymphokines in human giardiasis. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP GOTTSTEIN, B (reprint author), UNIV ZURICH,INST PARASITOL,WINTERTHURERSTR 266A,CH-8057 ZURICH,SWITZERLAND. NR 18 TC 10 Z9 11 U1 0 U2 0 PU MMW MEDIZIN VERLAG GMBH PI MUNICH 80 PA NEUMARKTER STRASSE 18, W-8000 MUNICH 80, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD NOV-DEC PY 1991 VL 19 IS 6 BP 421 EP 426 DI 10.1007/BF01726454 PG 6 WC Infectious Diseases SC Infectious Diseases GA GW343 UT WOS:A1991GW34300009 PM 1816113 ER PT J AU ALEXANDER, HR DOHERTY, GM BLOCK, MI KRAGEL, PJ JENSEN, JC LANGSTEIN, HN WALKER, E NORTON, JA AF ALEXANDER, HR DOHERTY, GM BLOCK, MI KRAGEL, PJ JENSEN, JC LANGSTEIN, HN WALKER, E NORTON, JA TI SINGLE-DOSE TUMOR-NECROSIS-FACTOR PROTECTION AGAINST ENDOTOXIN-INDUCED SHOCK AND TISSUE-INJURY IN RATS SO INFECTION AND IMMUNITY LA English DT Article ID MANGANOUS SUPEROXIDE-DISMUTASE; CACHECTIN; TOXICITY; BACTEREMIA; INDUCTION AB Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,DIV RES RESOURCES,BETHESDA,MD 20892. NR 21 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1991 VL 59 IS 11 BP 3889 EP 3894 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GM530 UT WOS:A1991GM53000007 PM 1937748 ER PT J AU RULONG, S AGUAS, AP DASILVA, PP SILVA, MT AF RULONG, S AGUAS, AP DASILVA, PP SILVA, MT TI INTRAMACROPHAGIC MYCOBACTERIUM-AVIUM BACILLI ARE COATED BY A MULTIPLE LAMELLAR STRUCTURE - FREEZE-FRACTURE ANALYSIS OF INFECTED-MOUSE LIVER SO INFECTION AND IMMUNITY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; ELECTRON-TRANSPARENT ZONE; INTRACELLULARE; MICE; ULTRASTRUCTURE; PATHOGENICITY; MACROPHAGES; MICROSCOPY; COMPLEX; ROUGH AB We used freeze fracture electron microscopy to study the fine structure of Mycobacterium avium inside phagosomes of murine macrophages. M. avium-susceptible C57BL/6 mice were infected with M. avium by intraperitoneal inoculation of 10(8) viable bacilli. We studied the microanatomy of the mycobacteria in 3-month infections of mice, a situation in which bacillary multiplication is extensive. In these samples, freeze fracture revealed that intraphagosomal bacilli were surrounded by a multilamellar coat that was apposed to the cell wall. In thin sections, in contrast, the area corresponding to the coat showed no substructure and was electron transparent (the so-called electron-transparent zone that has been previously reported by others). The multiple lamellae resembled an onionlike assembly that was inserted in between the mycobacterial wall outer surface and the phagosomal membrane. Each lamella of the M. avium coat was made up of parallel straight fibrils with a width of 5 nm. A variable number of lamellae, sometimes up to 10 or more elements, coated individual bacilli. The multilamellar coat was absent around both extracellular M. avium and intramacrophagic M. avium after short-term (45-min) inoculation of mice. The supramolecular organization of the M. avium lamellar coat as viewed here by freeze fracture is similar to that of purified mycoside C (P. Draper, J. Gen. Microbiol. 83:431-433, 1974; K.-S. Kim, M. R. J. Salton, and L. Barksdale, J. Bacteriol. 125:739-743, 1976), a mycobacterial component currently known as glycopeptidolipid (W. W. Barrow and P. J. Brennan, J. Bacteriol. 150:381-384, 1982). We conclude that M. avium bacilli growing in macrophages are surrounded by multilamellar capsulelike structures that contain glycopeptidolipid molecules. C1 NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, MEMBRANE BIOL SECT, FREDERICK, MD 21702 USA. CTR EXPTL CYTOL INIC, P-4100 OPORTO, PORTUGAL. UNIV PORTO, ABEL SALAZAR INST BIOMED SCI, DEPT ANAT, P-4000 OPORTO, PORTUGAL. OI Aguas, Artur P/0000-0002-1487-9517 NR 31 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1991 VL 59 IS 11 BP 3895 EP 3902 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GM530 UT WOS:A1991GM53000008 PM 1937749 ER PT J AU PIMENTA, PFP DASILVA, PP NASH, T AF PIMENTA, PFP DASILVA, PP NASH, T TI VARIANT SURFACE-ANTIGENS OF GIARDIA-LAMBLIA ARE ASSOCIATED WITH THE PRESENCE OF A THICK CELL COAT - THIN-SECTION AND LABEL FRACTURE IMMUNOCYTOCHEMISTRY SURVEY SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL HUMAN INFECTIONS; FLIP; PROTEIN AB Giardia lamblia undergoes surface antigenic variation. The ultrastructural location of antigens on four different variants was studied by label fracture and immunocytochemistry with four monoclonal antibodies (MAbs), each of which recognized the predominant variant in a particular clone. Each Giardia clone and its reacting MAb showed similar findings. The entire surface of the organism was covered by a surface coat which contained the variant surface protein. The surface coat was densely and uniformly labeled. Unreacting MAbs failed to label the surface. Label-fractured Giardia trophozoites exposed to reactive MAb revealed a planar distribution of reactivity with no discernible relationship to visualized intramembranous particles. Unexpectedly, some Giardia trophozoites lacked a surface coat and consequently failed to react with the appropriate MAb. The biological relevance of coatless Giardia trophozoites is unknown. These findings localize the variant antigens to the surface coat of the parasite and identify a minority of the population which lacks a surface coat. C1 NCI,MATH BIOL LAB,MEMBRANE BIOL SECT,FREDERICK,MD 21701. RP PIMENTA, PFP (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 33 TC 35 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1991 VL 59 IS 11 BP 3989 EP 3996 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GM530 UT WOS:A1991GM53000021 PM 1937758 ER PT J AU GENTRYWEEKS, CR PROVENCE, DL KEITH, JM CURTISS, R AF GENTRYWEEKS, CR PROVENCE, DL KEITH, JM CURTISS, R TI ISOLATION AND CHARACTERIZATION OF BORDETELLA-AVIUM PHASE VARIANTS SO INFECTION AND IMMUNITY LA English DT Article ID MODIFIED HORNIBROOK MEDIUM; HEAT-LABILE TOXIN; ALCALIGENES-FAECALIS; VIBRIO-CHOLERAE; ENVELOPE PROTEINS; VIRULENCE FACTORS; ANTIGENIC MODULATION; DERMONECROTIC TOXIN; RESPIRATORY TRACTS; PERTUSSIS AB Two spontaneous phase variants of Bordetella avium were isolated at a frequency of 2 x 10(-4) by colony immunoblot assay of B. avium with antibody against B. avium dermonecrotic toxin. The two phase variants, designated GOBL309 and GOBL312, lack dermonecrotic toxin and four outer membrane proteins with molecular masses of 93, 48, 38, and 27 kDa but retain the ability to agglutinate guinea pig erythrocytes. The proteins which are not expressed by GOBL309 and GOBL312 correspond to five proteins which are phenotypically modulated in B. avium by growth in the presence of nicotinic acid or MgSO4. Growth of the phase variants in supplemented Stainer-Scholte media containing nicotinamide did not alter expression of these five proteins. Intranasal inoculation of the spontaneous phase variants into 3-day-old turkeys and reisolation of B. avium at 2 weeks postinoculation resulted in the recovery of B. avium which had the wild-type phenotype, colonized the turkey tracheas, and produced the four outer membrane proteins and dermonecrotic toxin. Hybridization of B. avium and B. avium-like chromosomal DNA with internal portions of the Bordetella pertussis virulence regulatory genes, bvgA and bvgS, revealed that B. avium and B. avium-like isolates contain 5.3- and 5.7-kb DNA fragments, respectively, which are homologous to bvgS. B. avium and B. avium-like chromosomal DNA failed to hybridize to B. pertussis bvgA. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP GENTRYWEEKS, CR (reprint author), WASHINGTON UNIV,DEPT BIOL,ST LOUIS,MO 63130, USA. FU NIAID NIH HHS [AI-28487, 1-F32-AI-07628] NR 64 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1991 VL 59 IS 11 BP 4026 EP 4033 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GM530 UT WOS:A1991GM53000026 PM 1937761 ER PT J AU CHEEVER, AW XU, YH SHER, A MACEDONIA, JG AF CHEEVER, AW XU, YH SHER, A MACEDONIA, JG TI ANALYSIS OF EGG GRANULOMA-FORMATION IN SCHISTOSOMA-JAPONICUM-INFECTED MICE TREATED WITH ANTIBODIES TO INTERLEUKIN-5 AND GAMMA-INTERFERON SO INFECTION AND IMMUNITY LA English DT Article ID MURINE SCHISTOSOMIASIS; HEPATIC-FIBROSIS; IMMUNOPATHOLOGY; EXPRESSION; MECHANISMS; MANSONI AB Schistosoma japonicum-infected mice were treated with antibodies to interleukin-5 (IL-5) or gamma interferon (IFN-gamma) from week 3 or 4 to week 10 of infection. Neither antibody affected egg production by the parasite, and neither had a consistent effect on the secretion of IFN-gamma or IL-5 cell-related cytokines by spleen cells from infected mice. Mice treated with antibody to murine IL-5 had only rare eosinophils in hepatic circumoval granulomas. Granulomas around single eggs were reduced in volume by a third, but hepatic fibrosis was unaffected. Treatment with antibody to murine IFN-gamma also reduced the size of granulomas and also did not affect hepatic fibrosis, which was measured as hydroxyproline. Our results, taken together with the studies of others, indicate that a complex interaction of cytokines affects granuloma size and that the size and fibrosis of granulomas are to some extent regulated independently. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI 052590] NR 22 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1991 VL 59 IS 11 BP 4071 EP 4074 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GM530 UT WOS:A1991GM53000032 PM 1834572 ER PT J AU SPITZER, RL DEVLIN, MJ WALSH, BT HASIN, D WING, R MARCUS, MD STUNKARD, A WADDEN, T YANOVSKI, S AGRAS, S MITCHELL, J NONAS, C AF SPITZER, RL DEVLIN, MJ WALSH, BT HASIN, D WING, R MARCUS, MD STUNKARD, A WADDEN, T YANOVSKI, S AGRAS, S MITCHELL, J NONAS, C TI BINGE EATING DISORDER - TO BE OR NOT TO BE IN DSM-IV SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Editorial Material ID OBESITY C1 STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10027. UNIV MINNESOTA,DEPT PSYCHIAT,MINNEAPOLIS,MN 55455. UNITED WEIGHT CONTROL CORP,PROGRAM DEV,NEW YORK,NY. COLUMBIA UNIV,CLIN PSYCHIAT,NEW YORK,NY 10027. UNIV PENN,PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 10 TC 59 Z9 60 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 1991 VL 10 IS 6 BP 627 EP 629 DI 10.1002/1098-108X(199111)10:6<627::AID-EAT2260100602>3.0.CO;2-4 PG 3 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA GN749 UT WOS:A1991GN74900001 ER PT J AU WUN, LM WEN, LP AF WUN, LM WEN, LP TI ASSESSING THE STATISTICAL CHARACTERISTICS OF THE MEAN ABSOLUTE ERROR OR FORECASTING SO INTERNATIONAL JOURNAL OF FORECASTING LA English DT Article DE MEAN ABSOLUTE ERROR; MEAN ABSOLUTE ERROR OF FORECASTING AB This paper assesses some general statistical characteristics of the mean absolute error of forecasting (MAEF). It shows that the MAEF is the sample estimate of the expected value of the absolute error of forecasting, and derives its mean and variance. The Central Limit Theorem is applied to establish the limiting distribution of the standardized MAEF. These results should be useful when the MAEF is used as a statistical performance criterion. C1 AT&T BELL LABS,TECH STAFF,HOLMDEL,NJ 07733. RP WUN, LM (reprint author), NCI,DIV CANC PREVENT & CONTROL,9000 ROCKVILLE PIKE,EPN-313,BETHESDA,MD 20892, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-2070 J9 INT J FORECASTING JI Int. J. Forecast. PD NOV PY 1991 VL 7 IS 3 BP 335 EP 337 DI 10.1016/0169-2070(91)90007-I PG 3 WC Economics; Management SC Business & Economics GA GW616 UT WOS:A1991GW61600007 ER PT J AU BLAHA, I NEMEC, J TOZSER, J OROSZLAN, S AF BLAHA, I NEMEC, J TOZSER, J OROSZLAN, S TI SYNTHESIS OF HOMOLOGOUS PEPTIDES USING FRAGMENT CONDENSATION - ANALOGS OF AN HIV PROTEINASE SUBSTRATE SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE FRAGMENT CONDENSATION; HIV PROTEINASE; SOLID PHASE PEPTIDE SYNTHESIS ID IMMUNODEFICIENCY-VIRUS PROTEASE; SOLID-PHASE; INHIBITOR; COMPLEX; ACID; AIDS AB Two protected peptides Boc-Val-Ser(Bzl)-Gln-Asn-Tyr(BrZ)OH and Boc-Val-Ser(Bzl)-Gln-Asn-Tyr(BrZ)-ProOH were synthesized on a resin substituted by 9-(hydroxymethyl)-2-fluoreneacetic acid. After cleavage with piperidine/DMF, desalting, and activation, these peptides were used for the synthesis of 11 analogs of an HIV proteinase nonapeptide substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 using fragment condensation in solid phase. The fragment condensation was made in an ultrasonic bath. Using only 2 equivalents of the activated peptide in a DMF solution, this reaction was complete in 2 h. All nonapeptides were assayed as substrates for HIV-1 and HIV-2 proteinases. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, CHEM SYNTH & ANAL LAB, FREDERICK, MD 21701 USA. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 25 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD NOV PY 1991 VL 38 IS 5 BP 453 EP 458 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT974 UT WOS:A1991GT97400007 PM 1802863 ER PT J AU STINSON, SF DELANEY, TF GREENBERG, J YANG, JC LAMPERT, MH HICKS, JE VENZON, D WHITE, DE ROSENBERG, SA GLATSTEIN, EJ AF STINSON, SF DELANEY, TF GREENBERG, J YANG, JC LAMPERT, MH HICKS, JE VENZON, D WHITE, DE ROSENBERG, SA GLATSTEIN, EJ TI ACUTE AND LONG-TERM EFFECTS ON LIMB FUNCTION OF COMBINED MODALITY LIMB SPARING THERAPY FOR EXTREMITY SOFT-TISSUE SARCOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 32ND ANNUAL MEETING OF THE AMERICAN SOC FOR THERAPEUTIC RADIOLOGY AND ONCOLOGY CY OCT, 1990 CL MIAMI, FL SP AMER SOC THERAPEUT RADIOL & ONCOL DE SOFT TISSUE SARCOMA; COMBINED MODALITY THERAPY; TREATMENT EFFECTS; LIMB FUNCTION ID CONSERVATIVE SURGERY; RANDOMIZED TRIAL AB A retrospective review is presented on 145 patients who underwent limb-sparing surgery and radiation therapy (with or without adjuvant chemotherapy) for their primary soft tissue sarcomas of the extremities on protocol between 1975 and 1986. The focus on our analysis was the acute and long term toxicity of treatment on limb function. The most common acute complication was skin reaction, occurring in 52 patients (36%). Long term (occurring after more than 1 year following all treatment) treatment complications in the extremity were as follows: bone fracture = 6%; contracture = 20%; pain requiring narcotics = 7%; edema greater than 2+ = 19%; moderate to severe decrease in range of motion = 32%; moderate to severe decrease in manual muscle strength = 20%; orthotic device required = 9%; cane or crutch required = 7%; chronic infection = 9%; and tissue induration = 57%. Three amputations for treatment complications were required. Inclusion of more than 50% of the joint in the radiation portal was associated with a higher frequency of contracture. High nominal standard dose (> 1760 rets, > 63 Gy at 1.8 Gy per fraction) resulted in more painful limbs as well as limbs with increased edema, decreased manual muscle strength, decreased range of motion, and skin telangiectasias. Edema was more often noted in patients with a longer radiation portal (greater than 35 cm), as was tissue induration. Chronic ulcer or infection was more frequently seen in patients with lower extremity tumors and when more than 75% of the extremity diameter was irradiated. Although chemotherapy given concurrent with radiation therapy was associated with a higher number of acute skin reactions, this did not appear to translate into increased long term morbidity. The percentage of patients ambulating without assistive devices and with mild or no pain was 84%. Careful attention to the techniques of radiation therapy may have a significant impact on minimizing acute and long term complications of limb sparing treatment for extremity soft tissue sarcoma. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,REHABIL MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 19 TC 129 Z9 134 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 NOV PY 1991 VL 21 IS 6 BP 1493 EP 1499 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA GR727 UT WOS:A1991GR72700012 PM 1938558 ER PT J AU UCKUN, FM MITCHELL, JB OBUZ, V PARK, CH WADDICK, K FRIEDMAN, N OUBAHA, L MIN, WS SONG, CW AF UCKUN, FM MITCHELL, JB OBUZ, V PARK, CH WADDICK, K FRIEDMAN, N OUBAHA, L MIN, WS SONG, CW TI RADIATION SENSITIVITY OF HUMAN B-LINEAGE LYMPHOID PRECURSOR CELLS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE RADIATION SENSITIVITY; LYMPHOID PRECURSOR CELL; B-LYMPHOCYTE ONTOGENY; B-LINEAGE LYMPHOPOIESIS ID HUMAN-BONE MARROW; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; PROGENITOR CELLS; HEMATOPOIETIC-CELLS; DOSE-RATE; RADIOBIOLOGICAL FEATURES; INVITRO RADIOSENSITIVITY; ANTIGEN EXPRESSION; SURFACE MOLECULES AB We studied the radiation sensitivity of eight immunophenotypically distinct B-lineage lymphoid precursor cell (LPC) lines of acute lymphoblastic leukemia (ALL) or fetal liver origin corresponding to discrete developmental stages of human B-cell ontogeny. The radiation sensitivity of B-lineage LPC showed a temporal association with the distinct stages of development. FL112 and FL114 fetal liver pro-B cells (Stage 0 B-lineage LPC) with germline immunoglobulin heavy chain (IgH) genes but rearranged T-cell receptor gamma (T-gamma) genes (D(o) of FL112 = 80.3 cGy, D(o) of FL114 = 50.2 cGy), REH ALL pre-pre-B cells (Stage I B-lineage LPC) with rearranged IgH and T-gamma genes (D(o) = 66.1 cGy), and NALM-6 ALL pre-pre-B/pre-B cells (Stage II B-lineage LPC) (D(o) = 50.5 cGy) corresponding to the earliest three stages of human B-lymphocyte development were the most radiation sensitive B-lineage LPC populations. By comparison, KM-3 ALL pre-B (Stage III B-lineage LPC) (D(o) = 194.7 cGy), HPB-NULL ALL pre-B (Stage IV B-lineage LPC) (D(o) = 134.6 cGy), and sIgM+ RAJI/NAMALWA early B (Stage Va/b B-lineage LPC) cell lines (D(o) of RAJI = 144.0 cGy, D(o) of NAMALWA = 165.5 cGy) corresponding to the later stages of human B-lymphocyte development were much more radiation resistant. These results indicate that the radiation sensitivity of B-lineage LPC decreases during maturation within the B-lineage lymphoid precursor pathway. By comparison, the S-phase index (% of S-phase cells as determined by DNA flow cytometry) or proliferation index (% S + G2M), cellular protein content, intracellular glutathione (GSH) level, glutathione-S-transferase (GST) activity, intracellular pH, or free cytoplasmic calcium concentration did not correlate with the radiation sensitivity of the B-lineage LPC. C1 UNIV MINNESOTA HOSP & CLIN,DEPT THERAPEUT RADIOL RADIAT ONCOL,CANC & LEUKEMIA BIOL SECT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT THERAPEUT RADIOL RADIAT ONCOL,RADIAT BIOL SECT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT PEDIAT,DIV HEMATOL ONCOL BONE MARROW TRANSPLANTAT,MINNEAPOLIS,MN 55455. NCI,RADIAT ONCOL BRANCH,EXPTL PHOTOTHERAPY SECT,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA-42633, R29 CA 42111, P01 CA-21737] NR 58 TC 25 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV PY 1991 VL 21 IS 6 BP 1553 EP 1560 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA GR727 UT WOS:A1991GR72700020 PM 1938565 ER PT J AU EPSTEIN, AH GLATSTEIN, E AF EPSTEIN, AH GLATSTEIN, E TI OUT ON A LIMB ON SARCOMAS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID SOFT-TISSUE SARCOMAS; RADIATION-THERAPY; EXTREMITY; QUALITY; LIFE C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RP EPSTEIN, AH (reprint author), NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 11 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV PY 1991 VL 21 IS 6 BP 1669 EP 1670 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA GR727 UT WOS:A1991GR72700034 PM 1938576 ER PT J AU FISHERMAN, JS CLINE, EM PLOWMAN, J QUINN, FR HAWKINS, MJ AF FISHERMAN, JS CLINE, EM PLOWMAN, J QUINN, FR HAWKINS, MJ TI TEREPHTHALAMIDINE - PAST AND FUTURE SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE TEREPHTHALAMIDINE AB Terephthalamidine (NSC 57155) (Fig. 1) is one of 800 terephthalanilides and related compounds which were synthesized and tested preclinically in the late 1950's and early 1960's. Based upon their activity against murine leukemias, some of these agents were tested briefly in clinical trials at that time. Despite the observation of responses, the compounds were dropped because of severe and unusual neurotoxicity. More recently, terephthalamidine has been screened for antitumor activity and chosen for further clinical investigation by the NCI's Project for the Review of Old Drugs (P.R.O.D.) because of its novel structure and spectrum of preclinical activity. The current availability of a plasma assay for the drug permits further study of its clinical pharmacokinetics and pharmacodynamics and, perhaps, the development of improved scheduling strategies. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP FISHERMAN, JS (reprint author), NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 1991 VL 9 IS 4 BP 295 EP 303 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA GX382 UT WOS:A1991GX38200001 PM 1804802 ER PT J AU CECKLER, TL KARINO, K KADOR, PF BALABAN, RS AF CECKLER, TL KARINO, K KADOR, PF BALABAN, RS TI MAGNETIC-RESONANCE-IMAGING OF THE RABBIT EYE - IMPROVED ANATOMICAL DETAIL USING MAGNETIZATION TRANSFER CONTRAST SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE SURFACE COIL; SPIN-LATTICE RELAXATION; MACROMOLECULES; COLLAGEN; LENS; SPIN-ECHO; GRADIENT-RECALLED ECHO ID SPIN RELAXATION; PROTON; WATER; TISSUE; LENS; H-1 AB Proton nuclear magnetic resonance (NMR) imaging previously has been used to examine structure and pathologies of the eye. The present study investigates the use of a saturation-transfer technique, which exploits water-macromolecular proton magnetic interactions, to enhance image contrast in the rabbit eye in vivo. Upon steady-state saturation of the macromolecular-proton magnetization, the water-proton signal intensity will decrease in proportion to the degree of water-macromolecular proton magnetic interaction. NMR images of the eye collected using saturation transfer are shown to have superior contrast compared to conventional NMR imaging techniques, in regard to numerous ocular structures, including the iris, ciliary bodies, muscle, lens, and cornea. C1 NEI,BETHESDA,MD 20892. RP CECKLER, TL (reprint author), NHLBI,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 26 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1991 VL 32 IS 12 BP 3109 EP 3113 PG 5 WC Ophthalmology SC Ophthalmology GA GP303 UT WOS:A1991GP30300015 PM 1938286 ER PT J AU FRANK, JA CHOYKE, PL AUSTIN, HA GIRTON, ME WEISS, G AF FRANK, JA CHOYKE, PL AUSTIN, HA GIRTON, ME WEISS, G TI GADOPENTETATE DIMEGLUMINE AS A MARKER OF RENAL-FUNCTION - MAGNETIC-RESONANCE-IMAGING TO GLOMERULAR-FILTRATION RATES SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT SYMP ON CONTRAST MEDIA RESEARCH ( CMR 91 ) CY JUL 08-12, 1991 CL CAMBRIDGE, ENGLAND SP BRACCO IND CHIM, BRISTOL MYERS SQUIBB PHARM, LAB GUERBET, MALLINCKRODT MED, NYCOMED, SCHERING, STERLING WINTHROP PHARM, ADV MAGNET, ALLIANCE PHARM, BERLEX LABS ID DYNAMIC GD-DTPA; MR; KIDNEY C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BETHESDA,MD. NCI,SURG ONCOL BRANCH,BETHESDA,MD 20892. NR 11 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 1991 VL 26 SU 1 BP S134 EP S136 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GQ306 UT WOS:A1991GQ30600046 PM 1808110 ER PT J AU GOLMAN BRASCH, RC KATZBERG, RW MORRIS, TW TWEEDLE, MF EVILL, CA MATTREY, RF LAUFFER VEXLER, VS FRANK, JA AF GOLMAN BRASCH, RC KATZBERG, RW MORRIS, TW TWEEDLE, MF EVILL, CA MATTREY, RF LAUFFER VEXLER, VS FRANK, JA TI MAGNETIC-RESONANCE-IMAGING AND THE KIDNEY - DISCUSSION SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 UNIV CALIF SAN FRANCISCO,DEPT RADIOL,SAN FRANCISCO,CA 94143. UNIV ROCHESTER,MED CTR,DEPT RADIOL,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT MED,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT UROL,ROCHESTER,NY 14642. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT CONTRAST MEDIA,NEW BRUNSWICK,NJ. MRI INST,DEPT RADIOL,SAN DIEGO,CA. ACAD SCI USSR,INST CHEM PHYS,MOSCOW V-71,USSR. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. FLINDERS UNIV,DEPT RADIOL,BEDFORD PK,SA 5042,AUSTRALIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 1991 VL 26 SU 1 BP S137 EP S138 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GQ306 UT WOS:A1991GQ30600047 ER PT J AU SUMMERFELT, AT ALPHS, LD WAGMAN, AMI FUNDERBURK, FR HIERHOLZER, RM STRAUSS, ME AF SUMMERFELT, AT ALPHS, LD WAGMAN, AMI FUNDERBURK, FR HIERHOLZER, RM STRAUSS, ME TI REDUCTION OF PERSEVERATIVE ERRORS IN PATIENTS WITH SCHIZOPHRENIA USING MONETARY FEEDBACK SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Note ID DORSOLATERAL PREFRONTAL CORTEX; CARD SORTING TEST; PHYSIOLOGIC DYSFUNCTION C1 UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. NIMH,SCHIZOPHRENIA RES BRANCH,BETHESDA,MD 20892. ANTECH INC,BALTIMORE,MD. DEPT VET AFFAIRS MED CTR,DEPT PSYCHIAT,PERRY POINT,MD. FU PHS HHS [40279] NR 14 TC 46 Z9 47 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 1991 VL 100 IS 4 BP 613 EP 616 DI 10.1037/0021-843X.100.4.613 PG 4 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA GM783 UT WOS:A1991GM78300021 PM 1757677 ER PT J AU AMBRUS, JL HANEIWICH, S CHESKY, L MCFARLAND, P ENGLER, RJ AF AMBRUS, JL HANEIWICH, S CHESKY, L MCFARLAND, P ENGLER, RJ TI IMPROVED INVITRO ANTIGEN-SPECIFIC ANTIBODY-SYNTHESIS IN 2 PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY TAKING AN ORAL CYCLOOXYGENASE AND LIPOXYGENASE INHIBITOR (KETOPROFEN) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE B-CELL; COMMON VARIABLE IMMUNODEFICIENCY; PROLIFERATION; ANTIBODY PRODUCTION; 5-LIPOXYGENASE; KETOPROFEN ID CELL GROWTH-FACTOR; HUMAN-LYMPHOCYTES; T-CELLS; B-CELLS; VARIED IMMUNODEFICIENCY; INTERFERON-GAMMA; HYPOGAMMAGLOBULINEMIA; PROSTAGLANDIN-E2; INTERLEUKIN-4; LEUKOTRIENES AB In the process of performing a previously published study examining B cell function in 16 patients with common variable immunodeficiency (CVI)(J ALLERGY CLIN IMMUNOL 1991;87:1138-49), we noted improved in vitro antibody (Ab) synthesis in a patient, H.B., while he was taking a cyclooxygenase and lipoxygenase inhibitor, ketoprofen. Addition of ketoprofen in vitro to B cells from patients with CVI resulted in improved proliferation and differentiation in four of five additional patients with CVI studied. One patient, besides H. B., M. K. B., whose B cells secreted increased amounts of antigen (Ag)-specific Ab in response to in vitro ketoprofen, underwent a trial of oral ketoprofen. M. K. B., like H. B., demonstrated improved in vitro Ag-specific Ab production while she was taking oral ketoprofen. No increase in serum Ab levels was noted in either patient taking ketoprofen, but both patients remained infection free during the time of their ketoprofen trials (H. B., 9 months, and M. K. B., 36 months). No improvement in in vitro Ag-specific Ab synthesis was noted when H. B. and M. K. B. took oral cyclooxygenase inhibitors (naproxen or ibuprofen). Thus, additional study is warranted to examine the role of lipoxygenase products of arachidonic acid in the B cell dysfunction of CVI. C1 NIAID,BETHESDA,MD 20892. MED UNIV S CAROLINA,CHARLESTON,SC 29425. WALTER REED ARMY MED CTR,DIV ALLERGY & IMMUNIZAT,WASHINGTON,DC 20307. RP AMBRUS, JL (reprint author), WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH MED,DIV RHEUMATOL,216 S KINGSHIGHWAY,ST LOUIS,MO 63110, USA. NR 34 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 1991 VL 88 IS 5 BP 775 EP 783 DI 10.1016/0091-6749(91)90185-Q PG 9 WC Allergy; Immunology SC Allergy; Immunology GA GQ452 UT WOS:A1991GQ45200013 PM 1955636 ER PT J AU HURD, SZ AF HURD, SZ TI WORKSHOP SUMMARY AND GUIDELINES - INVESTIGATIVE USE OF BRONCHOSCOPY, LAVAGE, AND BRONCHIAL BIOPSIES IN ASTHMA AND OTHER AIRWAY DISEASES SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID BRONCHOALVEOLAR LAVAGE; MAST-CELLS; MILD ASTHMA; ALLERGEN CHALLENGE; ANTIGEN CHALLENGE; MEDIATOR RELEASE; INFLAMMATION; EXERCISE; BRONCHOCONSTRICTION; PROSTAGLANDIN-D2 RP HURD, SZ (reprint author), NHLBI,DLD,WESTWOOD BLDG,ROOM 6A-15,BETHESDA,MD 20892, USA. NR 40 TC 94 Z9 94 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 1991 VL 88 IS 5 BP 808 EP 814 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA GQ452 UT WOS:A1991GQ45200017 ER PT J AU SHAMAY, A SOLINAS, S PURSEL, VG MCKNIGHT, RA ALEXANDER, L BEATTIE, C HENNIGHAUSEN, L WALL, RJ AF SHAMAY, A SOLINAS, S PURSEL, VG MCKNIGHT, RA ALEXANDER, L BEATTIE, C HENNIGHAUSEN, L WALL, RJ TI PRODUCTION OF THE MOUSE WHEY ACIDIC PROTEIN IN TRANSGENIC PIGS DURING LACTATION SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE TRANSGENIC ANIMALS; WHEY PROTEIN; LACTATION; MILK; AGALACTIA ID TISSUE PLASMINOGEN-ACTIVATOR; GENE PROMOTER; MILK; EXPRESSION; MICE; VISUALIZATION; SHEEP AB The mouse whey acidic protein (WAP) gene was introduced into the genome of pigs and its expression was analyzed in the mammary gland. Mouse WAP was detected in milk of lactating females from five lines at levels between .5 and 1.5 g/liter, thereby representing as much as 2% of the total milk proteins. The corresponding mRNA was expressed in mammary tissue at levels similar to those of pig beta-lactoglobulin and beta-casein. The pattern of WAP secretion in three pigs over a period of 6 wk was quantitatively similar to that of pig beta-lactoglobulin. From the eight transgenic pigs analyzed, three successfully completed one lactational period, but five pigs stopped lactating a few days after parturition. Our results show that it is possible to produce large quantities of a foreign protein in milk of pigs over a full lactational period. However, expression of WAP can compromise the mammary gland and render it nonfunctional. C1 USDA ARS,BELTSVILLE AGR RES CTR,BLDG 200,RM 16,BELTSVILLE,MD 20705. NIH,BIOCHEM & METAB LAB,BETHESDA,MD 20892. SWISS FED INST TECHNOL,FED INST TECHNOL,CH-8092 ZURICH,SWITZERLAND. UNIV ILLINOIS,COLL MED,CHICAGO,IL 60612. NR 26 TC 44 Z9 44 U1 0 U2 1 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD NOV PY 1991 VL 69 IS 11 BP 4552 EP 4562 PG 11 WC Agriculture, Dairy & Animal Science SC Agriculture GA GM762 UT WOS:A1991GM76200032 PM 1721617 ER PT J AU EICHACKER, PQ HOFFMAN, WD FARESE, A BANKS, SM KUO, GC MACVITTIE, TJ NATANSON, C AF EICHACKER, PQ HOFFMAN, WD FARESE, A BANKS, SM KUO, GC MACVITTIE, TJ NATANSON, C TI TNF BUT NOT IL-1 IN DOGS CAUSES LETHAL LUNG INJURY AND MULTIPLE ORGAN DYSFUNCTION SIMILAR TO HUMAN SEPSIS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CYTOKINE; PULMONARY INJURY; SEPTIC SHOCK ID TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; HUMAN VASCULAR ENDOTHELIUM; PROCOAGULANT ACTIVITY; ALVEOLAR MACROPHAGES; ESCHERICHIA-COLI; CANINE MODEL; INTERLEUKIN-1; CACHECTIN; BACTEREMIA AB We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies. Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60-mu-g/kg body wt, n = 8), IL-1 (1,000-mu-g/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls). Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study. Animals given IL-1 had a transient increase (P < 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study. Animals given TNF had early (0-4 h) decreases (P < 0.05) in arterial Po2, increases (P < 0.05) in physiological shunt fraction and alveolar-to-arterial Po2 gradient, and a high mortality rate (50%). In TNF animals, volume challenges at 4 h were associated (P < 0.05) with death and noncardiogenic pulmonary edema. In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P < 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days. Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial Po2. In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock. The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury. Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock. C1 CHIRON CORP,EMERYVILLE,CA 94608. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. DEF NUCL AGCY,ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. RP EICHACKER, PQ (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 46 TC 69 Z9 71 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1991 VL 71 IS 5 BP 1979 EP 1989 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA GP821 UT WOS:A1991GP82100050 PM 1761500 ER PT J AU HACKSTADT, T AF HACKSTADT, T TI PURIFICATION AND N-TERMINAL AMINO-ACID-SEQUENCES OF CHLAMYDIA-TRACHOMATIS HISTONE ANALOGS SO JOURNAL OF BACTERIOLOGY LA English DT Note ID OUTER-MEMBRANE PROTEIN; IDENTIFICATION; ENVELOPES AB DNA-binding proteins specific to Chlamydia trachomatis elementary bodies have been described and recently characterized as procaryotic histone analogs. I have developed an affinity purification procedure for the 18-kDa histone analog, Hc1, based on its affinity for polyanions. The availability of highly purified Hc1 has allowed for determination of its N-terminal amino acid sequence and should prove useful in studies of its biological function. The variable C. trachomatis histone analog not obtained by this procedure was electrophoresed onto Immobilon paper for sequencing. The N terminus of the variable histone was conserved among C. trachomatis serotypes L2, D, and B and was distinct from that of Hc1. C1 UNIV TEXAS,MED BRANCH,DEPT MICROBIOL,GALVESTON,TX 77550. UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77550. RP HACKSTADT, T (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 20 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1991 VL 173 IS 21 BP 7046 EP 7049 PG 4 WC Microbiology SC Microbiology GA GM344 UT WOS:A1991GM34400055 PM 1938908 ER PT J AU ZHU, YY SCHWARTZ, RJ CROW, MT AF ZHU, YY SCHWARTZ, RJ CROW, MT TI PHORBOL ESTERS SELECTIVELY DOWN-REGULATE CONTRACTILE PROTEIN GENE-EXPRESSION IN TERMINALLY DIFFERENTIATED MYOTUBES THROUGH TRANSCRIPTIONAL REPRESSION AND MESSAGE DESTABILIZATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; CHICKEN ACTIN GENES; KINASE-C; SKELETAL-MUSCLE; EVOLUTIONARY CONSERVATION; CULTURED MYOTUBES; MYRISTATE ACETATE; RIBOSOMAL-RNA; INTACT-CELLS; BETA-ACTIN AB Chronic exposure of differentiated avian skeletal muscle cells in culture to the phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (PMA), results in the selective disassembly of sarcomeric structures and loss of muscle-specific contractile proteins, leaving cytoskeletal structures and their associated proteins intact. We demonstrate here that these morphological and biochemical changes are accompanied by dramatic and selective decreases in the level of the mRNAs that encode the contractile proteins. We measured the effects of PMA on the transcriptional activity and mRNA stability of four contractile protein genes (alpha-cardiac and alpha-skeletal actin, cardiac troponin C [cTnC], and myosin light chain 1f [MLC1f]) and two nonmuscle genes (beta-cytoplasmic actin and the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase [GAPDH]). The transcriptional activity of the alpha-cardiac actin and cTnC genes dramatically decreased by 8 h after the addition of PMA, while other muscle and nonmuscle genes examined showed no change. Pulse-chase experiments of in vivo labeled RNA showed significant reductions in mRNA half-lifes for all the contractile protein mRNAs examined, while the half-lifes of beta-actin and GAPDH mRNA were unchanged. All of the above effects occurred under conditions in which cellular protein kinase C (PKC) levels had been reduced by > 90%. The fact that many of the contractile protein genes remained transcriptionally active despite the fact that the cells were unable to accumulate their mRNAs to any significant extent indicated that the treated cells were still committed to skeletal muscle differentiation. The selective changes in the stability of the contractile protein mRNAs suggest that the control of mRNA stability may be part of the normal regulatory program of skeletal muscle differentiation and that this control may be linked to the integrity of the contractile apparatus and mediated by second messenger pathways involving PKC activation. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP ZHU, YY (reprint author), BAYLOR COLL MED,DIV NEUROSCI,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL-38401] NR 43 TC 46 Z9 46 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1991 VL 115 IS 3 BP 745 EP 754 DI 10.1083/jcb.115.3.745 PG 10 WC Cell Biology SC Cell Biology GA GM780 UT WOS:A1991GM78000015 PM 1717491 ER PT J AU KENNEDY, C AF KENNEDY, C TI SOKOLOFF,LOUIS AT 3 SCORE AND 10 SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Editorial Material ID CEREBRAL GLUCOSE-UTILIZATION; METABOLIC-RATE; SYSTEM RP KENNEDY, C (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,RM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1991 VL 11 IS 6 BP 885 EP 889 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA GL515 UT WOS:A1991GL51500001 PM 1939383 ER PT J AU LIU, L CRISTIANO, AM SOUTHERS, JL REYNOLDS, JC BACHER, J BROWN, G GILLEY, RM TICE, TR BANKS, SM LORIAUX, LD CASSORLA, F AF LIU, L CRISTIANO, AM SOUTHERS, JL REYNOLDS, JC BACHER, J BROWN, G GILLEY, RM TICE, TR BANKS, SM LORIAUX, LD CASSORLA, F TI EFFECTS OF PITUITARY-TESTICULAR AXIS SUPPRESSION INUTERO AND DURING THE EARLY NEONATAL-PERIOD WITH A LONG-ACTING LUTEINIZING-HORMONE-RELEASING HORMONE ANALOG ON GENITAL DEVELOPMENT, SOMATIC GROWTH, AND BONE-DENSITY IN MALE CYNOMOLGUS MONKEYS IN THE 1ST 6 MONTHS OF LIFE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM GONADOTROPIN CONCENTRATIONS; MALE RHESUS-MONKEYS; TESTOSTERONE SECRETION; SEXUAL DEVELOPMENT; MACACA-MULATTA; GONADAL AXIS; AGONIST; FETAL; BLOCKADE; RAT AB The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRH(A)), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRH(A)-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRH(A) group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P < 0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH approximately-A group were significantly lower than those of the placebo group throughout the first 6 months of life (P < 0.05). By contrast, LHRH(A) treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRH(A) in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development. C1 NATL CTR RES RESOURCES, DEPT NUCL MED, BETHESDA, MD 20892 USA. SO RES INST, DIV CONTROL RELEASE, BIRMINGHAM, AL 35255 USA. NIAID, BETHESDA, MD 20892 USA. RP LIU, L (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N 262, BETHESDA, MD 20892 USA. NR 32 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1991 VL 73 IS 5 BP 1038 EP 1043 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GP140 UT WOS:A1991GP14000018 PM 1939516 ER PT J AU NYOMBA, BL BRAUTIGAN, DL SCHLENDER, KK WANG, W BOGARDUS, C MOTT, DM AF NYOMBA, BL BRAUTIGAN, DL SCHLENDER, KK WANG, W BOGARDUS, C MOTT, DM TI DEFICIENCY IN PHOSPHORYLASE-PHOSPHATASE ACTIVITY DESPITE ELEVATED PROTEIN PHOSPHATASE TYPE-1 CATALYTIC SUBUNIT IN SKELETAL-MUSCLE FROM INSULIN-RESISTANT SUBJECTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GLYCOGEN SYNTHESIS; INHIBITOR-2; INSULIN ACTION; PROTEIN PHOSPHORYLATION; PIMA INDIANS ID GLYCOGEN-SYNTHASE; CELLULAR-REGULATION; RAT-LIVER; METABOLISM; INVIVO; ENZYME; DEPHOSPHORYLATION; PURIFICATION; ACTIVATION; EXTRACTS AB Glycogen synthase is activated by protein phosphatase type-1 (PP-1). The spontaneous PP-1 activity accounts for only a small fraction of total PP-1 activity, which can be exposed by trypsin digestion of inhibitor proteins in the presence of Mn2+. We determined total PP-1 activity in muscle biopsies from insulin-sensitive and -resistant nondiabetic Pima Indians. Inhibitor-2 sensitive PP-1 represented 90% of total phosphatase activity. Spontaneous and total PP-1 activities were reduced in insulin resistant subjects (P < 0.05-0.01), suggesting that the reduced PP-1 activity is not the result of inhibition by trypsin-labile phosphatase regulatory subunits. This difference was further investigated by Western blots using two different antibodies. An antibody raised against the rabbit muscle PP-1 catalytic subunit was used to analyze muscle extracts concentrated by DEAE-Sepharose adsorption. An antibody raised against a peptide derived from the COOH-terminal end of the PP-1 catalytic subunit was used to analyze crude muscle extracts. Both antibodies recognized a PP-1 catalytic subunit of approximately 33 kD, which unexpectedly was more abundant in insulin-resistant subjects (P < 0.05-0.01). The increase in the tissue PP-1 protein content may be a response to compensate for the impairment in the enzyme activity. C1 NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016. BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. MED COLL OHIO,DEPT PHARMACOL,TOLEDO,OH 43699. FU NIDDK NIH HHS [DK31374] NR 43 TC 21 Z9 21 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1991 VL 88 IS 5 BP 1540 EP 1545 DI 10.1172/JCI115464 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GN727 UT WOS:A1991GN72700014 PM 1658044 ER PT J AU RADOVICK, S TICKNOR, CM NAKAYAMA, Y NOTIDES, AC RAHMAN, A WEINTRAUB, BD CUTLER, GB WONDISFORD, FE AF RADOVICK, S TICKNOR, CM NAKAYAMA, Y NOTIDES, AC RAHMAN, A WEINTRAUB, BD CUTLER, GB WONDISFORD, FE TI EVIDENCE FOR DIRECT ESTROGEN REGULATION OF THE HUMAN GONADOTROPIN-RELEASING-HORMONE GENE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GNRH; ESTROGEN; GENE REGULATION; HYPOTHALAMUS ID LHRH MESSENGER-RNA; RAT PROLACTIN GENE; INSITU HYBRIDIZATION; RESPONSIVE ELEMENT; TRANSCRIPTIONAL ACTIVATION; THYROID-HORMONE; RECEPTOR BINDS; PREOPTIC AREA; EXPRESSION; CELLS AB This study is an attempt to determine whether estrogen could directly regulate human gonadotropin-releasing hormone (GnRH) gene expression. Human GnRH expression vectors were constructed by fusing various 5' flanking regions of the human GnRH gene upstream of the luciferase reporter gene (LUC) or the thymidine kinase promoter linked to the chloramphenicol acetyltransferase reporter gene (CAT). These constructs were transiently transfected into a human choriocarcinoma cell line (JEG-3) and LUC or CAT activity was measured after either no treatment or treatment with various concentrations of estradiol. A stimulatory estrogen response element (ERE) was localized to a 32-bp region between -547 and -516 bp. To determine whether estrogen receptor bound to this region of the gene, we performed DNase I footprinting using purified calf uterine estrogen receptor. DNase I footprinting demonstrates a strong footprint between -567 and -514 bp of the human GnRH gene. In addition, an avidin-biotin complex DNA-binding assay demonstrated that a biotinylated DNA fragment containing -541 to -517 bp of the human GnRH gene bound S-35-labeled estrogen receptor as well as a biotinylated DNA fragment containing the xenopus vitellogenin ERE. On the other hand, the negative control biotinylated DNA fragment derived from adenovirus 5 bound insignificant amounts of S-35-labeled estrogen receptor. Both the GnRH ERE and vitellogenin ERE bound S-35-labeled estrogen receptor with high affinity (approximately 1 nM). These data indicate that the human GnRH gene contains an ERE sufficient to mediate a stimulatory response to estrogen in heterologous cells. Based upon these data we hypothesize that the human GnRH gene might also be directly regulated by estrogen in the hypothalamus, and that this regulation may explain the GnRH hypersecretion observed at the time of the preovulatory luteinizing hormone (LH) surge. C1 UNIV HOSP CLEVELAND,DIV PEDIAT,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,DIV ADULT ENDOCRINOL,CLEVELAND,OH 44106. NIDDKD,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED,ROCHESTER,NY 14642. NICHHD,BETHESDA,MD 20892. RP RADOVICK, S (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,W147,2119 ABINGTON RD,CLEVELAND,OH 44106, USA. NR 34 TC 88 Z9 89 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1991 VL 88 IS 5 BP 1649 EP 1655 DI 10.1172/JCI115479 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GN727 UT WOS:A1991GN72700029 PM 1939651 ER PT J AU MELCHERS, W MEIS, J ROSA, P CLAAS, E NOHLMANS, L KOOPMAN, R HORREVORTS, A GALAMA, J AF MELCHERS, W MEIS, J ROSA, P CLAAS, E NOHLMANS, L KOOPMAN, R HORREVORTS, A GALAMA, J TI AMPLIFICATION OF BORRELIA-BURGDORFERI DNA IN SKIN BIOPSIES FROM PATIENTS WITH LYME-DISEASE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; IXODES-DAMMINI TICKS; LINKED IMMUNOSORBENT-ASSAY; MUSEUM SPECIMENS; CULTIVATION; DIAGNOSIS AB To determine whether the polymerase chain reaction could contribute to a better diagnosis of Lyme disease, skin biopsy samples from patients suffering from erythema chronicum migrans or acrodermatitis chronica atrophicans were tested for the presence of Borrelia burgdorferi by a polymerase chain reaction assay, which was specific for European strains. The spirochete could not be detected microscopically in any of the 15 biopsy samples obtained from nine patients. However, B. burgdorferi could be isolated from seven of eight of these samples, which indicated the presence of spirochetes. Using a nested polymerase chain reaction, we were able to detect B. burgdorferi-specific sequences in 12 of the 15 biopsy samples. Biopsy samples from three of four patients with erythema chronicum migrans and four of five patients with acrodermatitis chronica atrophicans were found to be positive for B. burgdorferi. The spirochete could be isolated from the biopsy sample, from a patient with erythema chronicum migrans who tested negative, which suggests a false-negative polymerase chain reaction result probably on account of the low number of spirochetes present in the lesion. The positive polymerase chain reaction for lesions from patients with acrodermatis chronica atrophicans supports the concept that B. burgdorferi can persist in the skin over a long period of time. From these results, it was concluded that the polymerase chain reaction is a valuable technique for the diagnosis of Lyme disease. C1 MAASLAND HOSP,DEPT MED MICROBIOL,SITTARD,NETHERLANDS. UNIV HOSP ROTTERDAM,DEPT VIROL,ROTTERDAM,NETHERLANDS. NIH,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. RP MELCHERS, W (reprint author), UNIV HOSP NIJMEGEN,DEPT MED MICROBIOL,POB 9101,6500 HB NIJMEGEN,NETHERLANDS. RI Meis, Jacques/A-9241-2010; Melchers, Willem/C-8819-2015 OI Meis, Jacques/0000-0003-3253-6080; Melchers, Willem/0000-0002-5446-2230 NR 36 TC 78 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1991 VL 29 IS 11 BP 2401 EP 2406 PG 6 WC Microbiology SC Microbiology GA GK777 UT WOS:A1991GK77700008 PM 1774243 ER PT J AU HADDY, TB ADDE, MA MAGRATH, IT AF HADDY, TB ADDE, MA MAGRATH, IT TI CNS INVOLVEMENT IN SMALL NONCLEAVED-CELL LYMPHOMA - IS CNS DISEASE PER SE A POOR PROGNOSTIC SIGN SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS LYMPHOMA; COMBINED MODALITY TREATMENT; AMERICAN BURKITTS-LYMPHOMA; HIGH-DOSE METHOTREXATE; CHILDHOOD; CHEMOTHERAPY; CHILDREN; CYCLOPHOSPHAMIDE; IRRADIATION; PROPHYLAXIS C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 30 TC 37 Z9 39 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1991 VL 9 IS 11 BP 1973 EP 1982 PG 10 WC Oncology SC Oncology GA GM830 UT WOS:A1991GM83000009 PM 1941056 ER PT J AU LONGO, DL DUFFEY, PL DEVITA, VT WESLEY, MN HUBBARD, SM YOUNG, RC AF LONGO, DL DUFFEY, PL DEVITA, VT WESLEY, MN HUBBARD, SM YOUNG, RC TI THE CALCULATION OF ACTUAL OR RECEIVED DOSE INTENSITY - A COMPARISON OF PUBLISHED METHODS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHEMOTHERAPY; LYMPHOMA C1 NCI,INT CANC INFORMAT CTR,FREDERICK,MD 21701. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. FOX CHASE CANC INST,PHILADELPHIA,PA 19111. RP LONGO, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 576,FREDERICK,MD 21702, USA. NR 10 TC 112 Z9 112 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1991 VL 9 IS 11 BP 2042 EP 2051 PG 10 WC Oncology SC Oncology GA GM830 UT WOS:A1991GM83000017 PM 1941063 ER PT J AU STEVENSON, HC GREEN, I HAMILTON, JM CALABRO, BA PARKINSON, DR AF STEVENSON, HC GREEN, I HAMILTON, JM CALABRO, BA PARKINSON, DR TI LEVAMISOLE - KNOWN EFFECTS ON THE IMMUNE-SYSTEM, CLINICAL-RESULTS, AND FUTURE APPLICATIONS TO THE TREATMENT OF CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID SOUTHWEST-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; SURGICAL ADJUVANT THERAPY; BACILLUS CALMETTE-GUERIN; ADVANCED BREAST-CANCER; STUDY-GROUP TRIAL; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; CHEMO-IMMUNOTHERAPY; MALIGNANT-MELANOMA C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP STEVENSON, HC (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892, USA. NR 82 TC 92 Z9 93 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1991 VL 9 IS 11 BP 2052 EP 2066 PG 15 WC Oncology SC Oncology GA GM830 UT WOS:A1991GM83000018 PM 1941064 ER PT J AU UHDE, TW TANCER, ME BLACK, B BROWN, TM AF UHDE, TW TANCER, ME BLACK, B BROWN, TM TI PHENOMENOLOGY AND NEUROBIOLOGY OF SOCIAL PHOBIA - COMPARISON WITH PANIC DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT SYMP AT THE 11TH NATIONAL CONF ON ANXIETY DISORDERS - SOCIAL PHOBIA : ADVANCES IN UNDERSTANDING AND TREATMENT CY APR 00-07, 1991 CL CHICAGO, IL ID ANXIETY DISORDERS; THEORETICAL IMPLICATIONS; SLEEP; PHENELZINE; ATTACKS; CLASSIFICATION; DEPRESSION; ALPRAZOLAM; SYMPTOMS; ATENOLOL C1 UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC 27514. RP UHDE, TW (reprint author), NIMH,INTRAMURAL RES PROGRAM,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECTIVE DISORDERS SECT,BETHESDA,MD 20892, USA. NR 56 TC 41 Z9 41 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1991 VL 52 SU S BP 31 EP 40 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA GR306 UT WOS:A1991GR30600006 PM 1757454 ER PT J AU BARTOLOTTI, LJ PEDERSEN, LG CHARIFSON, PS AF BARTOLOTTI, LJ PEDERSEN, LG CHARIFSON, PS TI LONG-RANGE NONBONDED ATTRACTIVE CONSTANTS FOR SOME CHARGED ATOMS SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; FORCE-FIELD; SIMULATIONS; ALKALI; MECHANICS; PROTEINS; SYSTEM; WATER AB Employing the hydrodynamic formulation of time-dependent Kohn-Sham theory, long range dispersion constants are calculated for some metal ions. We show that these quantities, when used in molecular mechanics calculations or molecular dynamics simulations, lead to excellent results. C1 CRAY RES INC,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. RP BARTOLOTTI, LJ (reprint author), UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 19 TC 24 Z9 24 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD NOV PY 1991 VL 12 IS 9 BP 1125 EP 1128 DI 10.1002/jcc.540120910 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA GN724 UT WOS:A1991GN72400009 ER PT J AU DOUEK, P TURNER, R PEKAR, J PATRONAS, N LEBIHAN, D AF DOUEK, P TURNER, R PEKAR, J PATRONAS, N LEBIHAN, D TI MR COLOR MAPPING OF MYELIN FIBER ORIENTATION SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE MAGNETIC RESONANCE IMAGING; TECHNIQUES; BRAIN; DISEASES; MYELIN ID INTRAVOXEL INCOHERENT MOTION; WHITE MATTER; DIFFUSION; PERFUSION; BRAIN; WATER AB Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders. C1 NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,NRC,IN VIVO NUCL MAGNET RESONANCE RES CTR,BETHESDA,MD 20892. RI Turner, Robert/C-1820-2008 NR 22 TC 176 Z9 180 U1 1 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 1991 VL 15 IS 6 BP 923 EP 929 DI 10.1097/00004728-199111000-00003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GN911 UT WOS:A1991GN91100003 PM 1939769 ER PT J AU WAGNER, RC ANDREWS, SB AF WAGNER, RC ANDREWS, SB TI CRYOFIXATION OF VASCULAR ENDOTHELIUM SO JOURNAL OF ELECTRON MICROSCOPY TECHNIQUE LA English DT Article DE CRYOFIXATION; ENDOTHELIUM; BLOOD VESSELS; ULTRASTRUCTURE ID ELECTRON-MICROSCOPY; RETE MIRABILE; CELLS; ULTRASTRUCTURE; FIXATION; VESICLES; SECTIONS; CAVEOLAE; SYSTEM; NUMBER AB Cryofixation refers to the immobilization of tissue components by the rapid removal of heat from the specimen, so that the structure is interred and stabilized in a natural embedding medium, namely, frozen (amorphous or microcrystalline) tissue water. Cryofixation is now often used as a complement to the more traditional fixation methods, especially when the cell structure is delicate or dynamic and may be inaccurately preserved by the slow selective action of chemical fixatives. Vascular endothelial cells are specialized for transcellular transport and for the regulation of blood flow and composition. The dynamic and labile subcellular organization of these cells, presumably reflecting these functional specializations, makes them ideal candidates for cryofixation. Several different types of endothelial cells were directly frozen at temperatures below 20 degrees Kelvin by pressing them against a liquid-helium-cooled block. These samples were subsequently processed for structural analysis by freeze-substitution. Detailed rationales, designs, and protocols are described for both freezing and freeze-substitution. Electron micrographs of cryofixed arterial and venous capillaries (rete mirabile of the American eel), iliac vein (rabbit), and cultured endothelium from the iliac vein (human) reveal that the organization of the characteristic intracellular membrane system of endothelial vesicles is qualitatively similar to that seen in chemically fixed endothelium, especially with regard to the inter-connection of clusters of individual vesicles to form elaborate networks. The luminal and abluminal networks are not in communication, at least not in static images. Quantitatively, however, most directly frozen endothelial cells have far fewer vesicular profiles than comparable glutaraldehyde-fixed cells. The differences can be explained by presuming that the rapid action of cryofixation (approximately 1 msec) gives a more accurate picture of the vesicular network because it captures the transient structure of labile or dynamic membranes. C1 NIH,NEUROBIOL LAB,BETHESDA,MD 20205. RP WAGNER, RC (reprint author), UNIV DELAWARE,SCH LIFE & HLTH SCI,NEWARK,DE 19716, USA. NR 36 TC 5 Z9 5 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 0741-0581 J9 J ELECTRON MICR TECH PD NOV PY 1991 VL 19 IS 3 BP 276 EP 290 DI 10.1002/jemt.1060190304 PG 15 WC Biology; Microscopy SC Life Sciences & Biomedicine - Other Topics; Microscopy GA GJ661 UT WOS:A1991GJ66100003 PM 1795182 ER PT J AU MADRIGAL, JA BELICH, MP BENJAMIN, RJ LITTLE, AM HILDEBRAND, WH MANN, DL PARHAM, P AF MADRIGAL, JA BELICH, MP BENJAMIN, RJ LITTLE, AM HILDEBRAND, WH MANN, DL PARHAM, P TI MOLECULAR DEFINITION OF A POLYMORPHIC ANTIGEN (LA45) OF FREE HLA-A AND HLA-B HEAVY-CHAINS FOUND ON THE SURFACES OF ACTIVATED B-CELL AND T-CELL SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-I MOLECULES; HUMAN LYMPHOCYTES; PEPTIDE; INVIVO; BETA-2-MICROGLOBULIN; MECHANISMS; EXPRESSION; ALLELES; INVITRO; FAMILY AB A monomorphic monoclonal antibody (LA45 antibody) reactive with "a new activation-induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek-Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha-1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha-1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin-activated T cells. We hypothesize the free heavy chains result from dissociation of beta-2-microglobulin from subpopulations of empty HLA-A,B molecules, or molecules with weakly bound peptides, that vary in size depending on cellular activation and peptide supply. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT CELL BIOL,BECKMAN LABS STRUCT BIOL,STANFORD,CA 94305. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NCI,VIRAL CARCINOGENESIS LAB,IMMUNOGENET SECT,FREDERICK,MD 21701. FU NIAID NIH HHS [AI-07290-06] NR 45 TC 77 Z9 79 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1991 VL 174 IS 5 BP 1085 EP 1095 DI 10.1084/jem.174.5.1085 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GM803 UT WOS:A1991GM80300013 PM 1940790 ER PT J AU KENNY, JJ OCONNELL, C SIECKMANN, DG FISCHER, RT LONGO, DL AF KENNY, JJ OCONNELL, C SIECKMANN, DG FISCHER, RT LONGO, DL TI SELECTION OF ANTIGEN-SPECIFIC, IDIOTYPE-POSITIVE B-CELLS IN TRANSGENIC MICE EXPRESSING A REARRANGED M167-MU HEAVY-CHAIN GENE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNE-RESPONSE; SOMATIC MUTATION; ANTIBODY-RESPONSE; REGION GENES; ADULT MICE; PHOSPHORYLCHOLINE; PHOSPHOCHOLINE; REPERTOIRE; MOUSE; DIVERSITY AB Flow cytometric analysis of antigen-specific, idiotype-positive (id+), B cell development in transgenic mice expressing a rearranged M167-mu-gene shows that large numbers of phosphocholine (PC)-specific, M167-id+ B cells develop in the spleen and bone marrow of these mice. Random rearrangement of endogenous V-kappa-genes, in the absence of a subsequent receptor-driven selection, should give rise to equal numbers of T15- and M167-id+ B cells. The observed 100-500-fold amplification of M167-id+ B cells expressing an endogenous encoded V-kappa-24J-kappa-5 light chain in association with the M167 V(H)1-id transgene product appears to be an antigen driven, receptor-mediated process, since no amplification of non-PC-binding M167 V(H)1/V-kappa-22, T15-id+ B cells occurs in these mu-only transgenic mice. The selection and amplification of antigen-specific, M167-id+ B cells requires surface expression of the mu-transgene product; thus, no enhancement of M167-id+ B cells occurs in the M167-mu-DELTA-mem-transgenic mice, which cannot insert the mu-transgene product into the B cell membrane. Surprisingly, no selection of PC-specific B cells occurs in M167-kappa-transgenic mice although large numbers of B cells expressing a crossreactive M167-id are present in the spleen and bone marrow of these mice. The failure to develop detectable numbers of M167-id+, PC-specific B cells in M167-kappa-transgenic mice may be due to a very low frequency of M167-V(H)-region formation during endogenous rearrangement of V(H)1 to D-J(H) segments. The somatic generation of the M167 version of a rearranged V(H)1 gene may occur in less than one of every 105 bone marrow B cells, and a 500-fold amplification of this M167-Id+ B cell would not be detectable by flow cytometry even though the anti-PC antibody produced by these B cells is detectable in the serum of M167-kappa-transgenic mice after immunization with PC. C1 USN,MED RES INST,BETHESDA,MD 20814. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP KENNY, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,POB B,BLDG 567,RM 227,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 56 TC 22 Z9 22 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1991 VL 174 IS 5 BP 1189 EP 1201 DI 10.1084/jem.174.5.1189 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GM803 UT WOS:A1991GM80300024 PM 1940797 ER PT J AU BARR, PJ GREEN, KM GIBSON, HL BATHURST, IC QUAKYI, IA KASLOW, DC AF BARR, PJ GREEN, KM GIBSON, HL BATHURST, IC QUAKYI, IA KASLOW, DC TI RECOMBINANT PFS25 PROTEIN OF PLASMODIUM-FALCIPARUM ELICITS MALARIA TRANSMISSION-BLOCKING IMMUNITY IN EXPERIMENTAL-ANIMALS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIBODIES; VACCINE; IMMUNOGENICITY; SAFETY AB Pfs25 is a sexual stage antigen of Plasmodium falciparum that is expressed on the surface of zygote and ookinete forms of the parasite. Monoclonal antibodies directed against native Pfs25 can block completely the development of P. falciparum oocysts in the midgut of the mosquito vector. Thus, this 25-kD protein is a potential vaccine candidate for eliciting transmission-blocking immunity in inhabitants of malaria endemic regions. We have synthesized, by secretion from yeast, a polypeptide analogue of Pfs25 that reacts with conformation-dependent monoclonal antibodies, and elicits transmission-blocking antibodies when used to immunize mice and monkeys in conjunction with a muramyl tripeptide adjuvant. Our results suggest the further evaluation of recombinant DNA-derived Pfs25 in transmission-blocking vaccination studies in humans. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP BARR, PJ (reprint author), CHIRON CORP,MOLEC BIOL,4560 HORTON ST,EMERYVILLE,CA 94608, USA. NR 17 TC 118 Z9 125 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1991 VL 174 IS 5 BP 1203 EP 1208 DI 10.1084/jem.174.5.1203 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GM803 UT WOS:A1991GM80300025 PM 1940798 ER PT J AU HE, XS BROSSI, A AF HE, XS BROSSI, A TI N-DEMETHYLATION OF (+/-)-6-BETA-ACETOXY-3-TROPINONE - SYNTHESIS OF (+/-)-6-BETA-ACETOXYNORTROPANE SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article AB Nortropinone 5, prepared from 3 by N-demethylation with trichloroethyl chloroformate, followed by deprotection of carbamate 4 with zinc in acetic acid, served as a starting material to prepare the N-protected 6-acetoxy ketones 7 and 9-12, and alcohols 6 and B. Nortropane 16 was prepared from 3 by decarbonylation via dithioketal 13 followed by N-demethylation, and from 10 by decarbonylation via dithioketal 14. When ethanol was used in the desulfurization of 14 instead of tetrahydrofuran, substantial amounts of the N-ethylated amine 17 were produced. RP HE, XS (reprint author), NIDDK,STRUCT BIOL LAB,NAT PROD SECT,BETHESDA,MD 20892, USA. NR 11 TC 8 Z9 9 U1 2 U2 3 PU HETERO CORPORATION PI TAMPA PA BOX 20285, TAMPA, FL 33622-0285 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD NOV PY 1991 VL 28 IS 7 BP 1741 EP 1746 PG 6 WC Chemistry, Organic SC Chemistry GA HU847 UT WOS:A1991HU84700016 ER PT J AU DSA, A COHEN, LA AF DSA, A COHEN, LA TI 4,5-DIMETHYLIMIDAZOLE - A CORRECTION AND ALTERNATIVE SYNTHESIS SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID COMPLEXES AB Fractional vacuum distillation of the product obtained from thermal condensation of acetoin with formamide is a formic acid complex of 4,5-dimethylimidazole, and not the expected free base. The H-1 and C-13 nmr spectra suggest that the product may be closer to a 1:1 hydrogen-bonded adduct than to a true salt. Commercial 4-hydroxymethyl-5-methylimidazole is converted quantitatively to the 4-chloromethyl derivative with thionyl chloride; hydrogenolysis of the latter compound provides 4,5-dimethylimidazole in an overall 80-90% yield, doubling the yield obtained by the classical method. RP DSA, A (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 10 TC 12 Z9 12 U1 0 U2 3 PU HETERO CORPORATION PI TAMPA PA BOX 20285, TAMPA, FL 33622-0285 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD NOV PY 1991 VL 28 IS 7 BP 1819 EP 1820 PG 2 WC Chemistry, Organic SC Chemistry GA HU847 UT WOS:A1991HU84700030 ER PT J AU FINE, JS KRUISBEEK, AM AF FINE, JS KRUISBEEK, AM TI THE ROLE OF LFA-1 ICAM-1 INTERACTIONS DURING MURINE LYMPHOCYTE-T DEVELOPMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THYMIC EPITHELIAL-CELLS; ADHESION MOLECULE-1 ICAM-1; HEMATOPOIETIC STEM-CELLS; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; SURFACE GLYCOPROTEIN; PRECURSOR CELLS; IMMUNE-SYSTEM; FETAL THYMUS; B-CELLS AB We have examined the expression and function of the cell adhesion molecules LFA-1 (CD11a/CD18), ICAM-1 (CD54), and ICAM-2 in murine fetal thymic ontogeny and in the adult thymus. On fetal days 14 and 15, 40 to 50% of thymocytes coexpress high levels of LFA-1 and ICAM-1, as determined by flow cytometry. By day 16, more than 90% of fetal thymocytes are LFA-1+ ICAM-1hi, and all IL-2R+ cells are located in this population. Although LFA-1 expression remains unchanged thereafter, ICAM-1 expression appears to be differentially regulated in different thymocyte subpopulations, with CD4+8+ cells being ICAM-1lo and CD4-8- thymocytes remaining ICAM-1hi. ICAM-2 surface expression is dull on both fetal and adult thymocytes. Surprisingly, the expression of ICAM-1 is differentially up-regulated on T cells having a mature phenotype in thymus and in peripheral lymphoid organs, with CD8+ T cells bearing the highest amount of surface ICAM-1. Addition of anti-ICAM-1 or anti-LFA-1 antibodies to fetal thymic organ cultures results in the impaired generation of CD4+8+ cells. These results indicate that LFA-1/ICAM-1 interactions facilitate murine thymic development and suggest that cell adhesion molecules mediate important events in T cell differentiation. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NR 60 TC 113 Z9 115 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 2852 EP 2859 PG 8 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000005 PM 1680920 ER PT J AU TAKAHAMA, Y SHARROW, SO SINGER, A AF TAKAHAMA, Y SHARROW, SO SINGER, A TI EXPRESSION OF AN UNUSUAL T-CELL RECEPTOR (TCR)-V-BETA REPERTOIRE BY LY-6C+ SUBPOPULATIONS OF CD4+ AND OR CD8+ THYMOCYTES - EVIDENCE FOR A DEVELOPMENTAL RELATIONSHIP BETWEEN LY-6C+ THYMOCYTES AND CD4-CD8-TCR-ALPHA-BETA+ THYMOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ADULT MURINE THYMUS; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; CD4-CD8 THYMOCYTES; ANTIGEN RECEPTOR; PRECURSOR CELLS; LYMPHOCYTES-T; B-CELLS; MOUSE AB A novel thymocyte subpopulation expressing an unusual TCR repertoire was identified by high surface expression of the Ly-6C Ag. Ly-6C+ thymocytes were distributed among all four CD4/CD8 thymocyte subsets, and represented a readily identifiable subpopulation within each one. Ly-6C+ thymocytes express TCR-alpha-beta, arise late in ontogeny, and appear in the CD4/CD8 developmental pathway after birth in a sequence that resembles that followed by conventional Ly-6C- cells during fetal ontogeny. Most interestingly, adult Ly-6C+ thymocytes express an unusual TCR-V-beta repertoire that is identical to that expressed by CD4-CD8-TCR-alpha-beta+ thymocytes in its overexpression of TCR-V-beta-68 and in its expression of some potentially autoreactive TCR-V-beta specificities. This unusual TCR-V-beta repertoire was even expressed by Ly-6C+ thymocytes contained within the CD4+CD8- 'single positive' thymocyte subset. Thus, expression of this unusual TCR-V-beta repertoire is not limited to CD4-CD8- thymocytes, and is unlikely to be a consequence of their double negative phenotype. Rather, we think that Ly-6C+TCR-alpha-beta+ thymocytes and CD4-CD8-TCR-alpha-beta+ are developmentally interrelated, a conclusion supported by several lines of evidence including the selective failure of both Ly-6C+ and CD4-CD8-TCR-alpha-beta+ thymocyte subsets to appear in TCR-beta transgenic mice. In contrast, peripheral Ly-6C+ T cells are developmentally distinct from Ly-6C+ thymocytes in that peripheral Ly-6C+ T cells expressed a conventional TCR-V-beta repertoire and developed normally in TCR-beta transgenic mice in which Ly-6C+ thymocytes failed to arise. We conclude that: 1) expression of a skewed TCR-V-beta repertoire is a characteristic of Ly-6C+TCR-alpha-beta+ thymocytes as well as CD4-CD8-TCR-alpha-beta+ thymocytes, and is not unique to thymocytes expressing neither CD4 nor CD8 accessory molecules; and 2) Ly-6C+ thymocytes are developmentally linked to CD4-CD8-TCR-alpha-beta+ thymocytes, but not to Ly-6C+ peripheral T cells. We suggest that Ly-6C+TCR-alpha-beta+ thymocytes are not the developmental precursors of Ly-6C+ peripheral T cells, but rather may be the developmental precursors of CD4-CD8-TCR-alpha-beta+ thymocytes. RP TAKAHAMA, Y (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B-17,BETHESDA,MD 20892, USA. NR 45 TC 62 Z9 62 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 2883 EP 2891 PG 9 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000010 PM 1680922 ER PT J AU CLOUSE, KA COSENTINO, LM WEIH, KA PYLE, SW ROBBINS, PB HOCHSTEIN, HD NATARAJAN, V FARRAR, WL AF CLOUSE, KA COSENTINO, LM WEIH, KA PYLE, SW ROBBINS, PB HOCHSTEIN, HD NATARAJAN, V FARRAR, WL TI THE HIV-1 GP120 ENVELOPE PROTEIN HAS THE INTRINSIC CAPACITY TO STIMULATE MONOKINE SECRETION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; HAMSTER OVARY CELLS; FACTOR-ALPHA; GLYCOPROTEIN GP120; SOLUBLE CD4; MONONUCLEAR PHAGOCYTES; SYNCYTIUM FORMATION; SURFACE-ANTIGENS; HUMAN-MONOCYTES AB Results and conclusions concerning the ability of HIV glycoprotein (gp) 120 to stimulate monokine secretion have been equivocal, based on observations using natural gpl20 derived from infected human cells and a Chinese hamster ovary (CHO) cell-derived recombinant fusion protein. Current studies were designed to determine whether differences in recombinant gpl20 proteins could result in failure to trigger monokine production. We found that natural gpl20 could stimulate monocytes to release TNF-alpha, IL-1-beta, IL-6, and granulocyte-macrophage-CSF, and this effect could be blocked with soluble CD4. Full-length rgpl20 either expressed from an adenovirus vector and purified from infected human cells, or derived from CHO cells, could function similarly. In contrast, full-length recombinant envelope protein expressed in a baculovirus system and a CHO cell-derived recombinant fusion protein tested previously, consistently failed to stimulate monokine production. The stimulatory capacity of both natural and full-length CHO cell-derived gpl20 was eliminated by heating at 100-degrees-C, and could be blocked with excess CHO cell-derived gpl20 fusion protein. Inasmuch as the baculovirus-expressed gpl20 and the CHO cell-derived recombinant fusion protein can bind to CD4, these results suggest that HIV gpl20 binding to CD4 on the monocyte surface may of itself be insufficient for stimulation of monokine secretion. Therefore, primary protein structure, as well as posttranslational protein modifications, may determine this activity. C1 PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES FACIL, DIV CANC TREATMENT, CYTOKINE MECHANISMS SECT, FREDERICK, MD 21701 USA. GEORGETOWN UNIV, WASHINGTON, DC 20007 USA. RP CLOUSE, KA (reprint author), US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL HFB-800, BETHESDA, MD 20205 USA. FU NCI NIH HHS [N01-CO-74102]; NIAID NIH HHS [N01-AI-726231V] NR 77 TC 161 Z9 163 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 2892 EP 2901 PG 10 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000011 PM 1918997 ER PT J AU RIECKMANN, P POLI, G FOX, CH KEHRL, JH FAUCI, AS AF RIECKMANN, P POLI, G FOX, CH KEHRL, JH FAUCI, AS TI RECOMBINANT GP120 SPECIFICALLY ENHANCES TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION AND IG SECRETION IN LYMPHOCYTES-B FROM HIV-INFECTED INDIVIDUALS BUT NOT FROM SERONEGATIVE DONORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL ACTIVATION; MONONUCLEAR PHAGOCYTES; IMMUNOGLOBULIN; MECHANISMS; EXPRESSION; RECEPTOR; INTERLEUKIN-1; RETROVIRUS; RESPONSES AB The effect of recombinant protein from the envelope (gp120) of the HIV on B lymphocytes purified from either HIV-infected individuals or healthy seronegative controls was examined. B cells from peripheral blood and lymph nodes of HIV-infected individuals spontaneously secreted TNF-alpha; this secretion was augmented by the presence of gpl20, whereas B cells from healthy seronegative donors failed to secrete significant levels of TNF-alpha in the presence or absence of gp120. In a coculture system of B cells and chronically HIV-infected T cells (ACH-2), where viral expression is largely mediated by TNF-alpha, gpl20 increased virus expression only if the B cells were obtained from HIV-infected individuals. The effects of gpl20 on viral expression in this system were not mediated via CD4 receptor binding or FcR binding of anti gpl20-gpl20 immune complexes. Besides its effect on cytokine production, gpl20 also stimulated Ig secretion in B cells from HIV-infected individuals, but not from normal donors. Finally, it was demonstrated by in situ hybridization that germinal centers of lymph nodes from HIV-infected individuals contain large amounts of HIV RNA that is in close proximity to germinal center B cells. These findings suggest that the hyperplastic germinal centers of lymph nodes provide an unique environment for virus expression and accumulation where gpl20 stimulates B cells to secrete HIV inductive cytokines, such as IL-6 and TNF-alpha, and thereby further enhances virus expression in infected cells in a paracrine manner. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 34 TC 84 Z9 85 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 2922 EP 2927 PG 6 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000015 PM 1918999 ER PT J AU LEVY, R MALECH, HL AF LEVY, R MALECH, HL TI EFFECT OF 1,25-DIHYDROXYVITAMIN-D3, LIPOPOLYSACCHARIDE, OR LIPOTEICHOIC ACID ON THE EXPRESSION OF NADPH OXIDASE COMPONENTS IN CULTURED HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST; HYDROGEN-PEROXIDE; INTERFERON-GAMMA; HUMAN NEUTROPHIL; ACTIVATES SECRETION; PLASMA-MEMBRANES; SUPEROXIDE; CELLS; STIMULATION AB Human blood monocytes in culture gradually lose their capability to produce superoxide when stimulated. Addition of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 2.5 ng/ml LPS, or 25 ng/ml lipotechoic acid (LTA) prevented this decrease in monocyte respiratory burst when added at initiation of culture. Monocytes cultured for 4 days in the presence of 1,25(OH)2D3, LPS, or LTA retained the ability to produce superoxide and 1,25(OH)2D3 actually increased the oxidative capacity compared with fresh monocytes. Furthermore, addition of 1,25(OH)2D3, LPS, or LTA to monocytes at day 4 of culture restored the oxidase activity by day 7 to the levels seen with fresh monocytes. Cytosol or membrane fractions from monocytes cultured with or without the agents indicated above were tested in a cell-free assay of superoxide production by mixing with fresh monocyte membrane or cytosol fractions, respectively. Membrane oxidase activity from these cultured monocytes showed only minimal changes regardless of the agent present or absent from the culture. However, the activity of cytosol fractions from these same cultured monocytes showed substantial differences depending upon the culture conditions and these changes correlated closely with changes in activity of the intact monocytes from which the cytosols were derived. Immunoblot analysis of monocyte membranes and cytosol was used to assess the amount of the 91-kDa and 22-kDa subunits of membrane oxidase cytochrome558 (gP91 and p22), and the 47-kDa and 67-kDa cytosol oxidase factors (p47 and p67) in the different culture conditions. The gp9l and p22 decreased during culture of monocytes, although the decrease was only apparent by 7 days in culture. When 1,25(OH)2D3, LPS, or LTA were present at the initiation of culture, then an increase in gp9l and p22 was seen as compared with fresh monocytes at day 4. When these agents were added at day 4 of culture, the levels of gp91 and p22 at day 7 were similar to fresh monocytes. The p67 cytosol oxidase component showed little change in amount by immunoblot regardless of the time in culture or whether 1,25(OH)2D3, LPS, or LTA were present. In contrast, the p47 cytosol oxidase factor decreased by day 4 of culture and was markedly depressed by day 7. Monocytes cultured in the presence of either 1,25(OH)2D3, LPS, or LTA preserved the expression of p47, whereas addition of these agents to monocytes at day 4 of culture restored the expression of p47 by day 7 to the level of fresh monocytes. Of all the oxidase components examined, the changes in expression of p47 correlated most closely with the changes of superoxide-generating activity of both cytosol and intact monocytes under all of the culture conditions examined. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. RP LEVY, R (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,CLIN BIOCHEM UNIT,INFECT DIS LAB,IL-84101 BEER SHEVA,ISRAEL. NR 32 TC 46 Z9 46 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 3066 EP 3071 PG 6 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000036 PM 1655903 ER PT J AU PEREZ, VL ROWE, T JUSTEMENT, JS BUTERA, ST JUNE, CH FOLKS, TM AF PEREZ, VL ROWE, T JUSTEMENT, JS BUTERA, ST JUNE, CH FOLKS, TM TI AN HIV-1-INFECTED T-CELL CLONE DEFECTIVE IN IL-2 PRODUCTION AND CA2+ MOBILIZATION AFTER CD3 STIMULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NORMAL HUMAN-LYMPHOCYTES; SIGNAL TRANSDUCTION; HTLV-III; NONCYTOPATHIC INFECTION; EXPRESSION; PROTEIN; ACTIVATION; RECEPTOR; AIDS AB A chronically HIV-1-infected T cell clone (J1.1) derived from Jurkat cells was developed that possesses defects in CD3 signaling. This clone was phenotypically determined to be CD4- and express a reduced surface density of CD3 as compared with a pool of uninfected Jurkat clones. Although J1.1 could be induced with TNF-alpha to produce HIV-1 particles, stimulation via the CD3 (T3-Ti) complex, using mAb cross-linking, had no effect on viral production. Further investigation revealed that J1.1 secreted approximately 20-fold less IL-2 than did uninfected Jurkat cells after anti-CD3 treatment. In addition, a separate defect in Ca2+ mobilization was noted in the HIV-1-infected J1.1 line when compared with uninfected Jurkat cells after anti-CD3 cross-linking. The cell line described offers a new model in which to study the mechanisms of several defects directly imposed by HIV-1 on CD3+ cells. C1 CTR DIS CONTROL, CTR INFECT DIS, DIV VIRAL & RICKETTSIAL DIS, RETROVIRUS DIS BRANCH, ATLANTA, GA 30333 USA. NATL NAVAL MED CTR, NAVAL MED RES INST, BETHESDA, MD 20892 USA. NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. NR 29 TC 87 Z9 88 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1991 VL 147 IS 9 BP 3145 EP 3148 PG 4 WC Immunology SC Immunology GA GL580 UT WOS:A1991GL58000047 PM 1833465 ER PT J AU AOKISEI, S OBRIEN, MC FORD, H FUJII, H GILBERT, DA COONEY, DA JOHNS, DG BRODER, S MITSUYA, H AF AOKISEI, S OBRIEN, MC FORD, H FUJII, H GILBERT, DA COONEY, DA JOHNS, DG BRODER, S MITSUYA, H TI INVITRO INHIBITION OF HEPATITIS-B VIRUS-REPLICATION BY 2',3'-DIDEOXYGUANOSINE, 2',3'-DIDEOXYINOSINE, AND 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE IN 2.2.15 (PR) CELLS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; PHASE-I TRIAL; HEPATOCELLULAR-CARCINOMA; 2',3'-DIDEOXYNUCLEOSIDES INVITRO; REVERSE-TRANSCRIPTASE; CELLULAR PHARMACOLOGY; ALPHA-INTERFERON; HTLV-III/LAV; T-CELLS AB Hep G2-derived hepatoblastoma cells (2.2.15), which actively produce hepatitis B virus (HBV), were cultured in the presence of 2',3'-dideoxyguanosine (ddG), 2',3'-dideoxyinosine, or 3'-azido-2',3'-dideoxythymidine (AZT). ddG was the most potent agent. It diminished viral replication by up to 95%, as assessed by the amount of episomal HBV DNA, without impairing cellular growth. AZT was the least effective against HBV. Northern blot analysis revealed no apparent difference in the pregenomic viral RNA profile, suggesting that these dideoxynucleosides suppress reverse transcription in the replicative cycle of HBV. The effect of varying the time of drug exposure showed that these agents can suppress HBV replication even when added late in culture. HBV replication in another 2.2.15 cell population of the same lineage was affected by ddG differently, which may enable the investigation of phenotypic or genetic alterations during culture. The present data suggest that some 2',3'-dideoxynucleosides can exert a potent antiviral activity against HBV in vitro, at least under certain circumstances, although the data do not prove that any of these agents have utility in patients with hepatitis. C1 NCI,CLIN ONCOL PROGRAM,MED CHEM LAB,BLDG 10,RM 13N248,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NCI,VIRAL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 59 TC 29 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1991 VL 164 IS 5 BP 843 EP 851 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GL294 UT WOS:A1991GL29400002 PM 1940465 ER PT J AU FISHER, WR ZECH, LA KILGORE, LL STACPOOLE, PW AF FISHER, WR ZECH, LA KILGORE, LL STACPOOLE, PW TI METABOLIC PATHWAYS OF APOLIPOPROTEIN-B IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - STUDIES WITH A [H-3] LEUCINE TRACER SO JOURNAL OF LIPID RESEARCH LA English DT Article DE COMPARTMENTAL MODELING; TRACER KINETICS ID LOW-DENSITY LIPOPROTEIN; TRIGLYCERIDE-RICH; PLASMA; HETEROGENEITY; TURNOVER; HYPERTRIGLYCERIDEMIA; HYPERLIPOPROTEINEMIA; SUBFRACTIONS; PRECURSORS; PROTEINS AB The kinetics of apolipoprotein B (apoB) were measured in seven studies in heterozygous, familial hypercholesterolemic subjects (FH) and in five studies in normal subjects, using in vivo tracer kinetic methodology with a [H-3]leucine tracer. Verv low density (VLDL) and low density lipoproteins (LDL) were isolated ultracentrifugally and LDL was fractionated into high and low molecular weight subspecies. ApoB was isolated, its specific radioactivity was measured, and the kinetic data were analyzed by compartmental modeling using the SAAM computer program. The pathways of apoB metabolism differ in FH and normal subjects in two major respects. Normals secrete > 90% of apoB as VLDL, while one-third of apoB is secreted as intermediate density lipoprotein IDL/LDL in FH. Normals lose 40-50% of apoB from plasma as VLDL/IDL, while FH subjects lose none, metabolizing all of apoB to LDL. In FH, there is also the known prolongation of LDL residence time. The leucine tracer, biosynthetically incorporated into plasma apoB, permits distinguishing the separate pathways by which the metabolism of apoB is channeled. ApoB synthesis and secretion require 1.3 h. ApoB is secreted by three routes: 1) as large VLDL where it is metabolized by a delipidation chain: 2) as a rapidly metabolized VLDL fraction converted to LDL; and 3) as IDL or LDL. ApoB is metabolized along two pathways. The delipidation chain processes large VLDL to small VLDL, IDL, and LDL. The IDL pathway channels nascent, rapidly metabolized VLDL and IDL particles into LDL. It thus provides a fast pathway for the entrance of apoB tracer into LDL, while the delipidation pathway is a slower route for channeling apoB through VLDL into LDL. LDL apoB is derived in almost equal amounts from both pathways, which feed predominantly into large LDL. Small LDL is a product of large LDL, and the major loss of LDL-apoB is from small LDL. (jlr) Two features of apoB metabolism in FH, the major secretory pathway through IDL and the absence of a catabolic loss of apoB from VLDL/IDL, greatly facilitate measuring the metabolic channeling of apoB into LDL. C1 UNIV FLORIDA,COLL MED,DEPT MED,GAINESVILLE,FL 32610. NIH,MATH BIOL LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [M-01RR00082]; NHLBI NIH HHS [HL-29394]; NIDDK NIH HHS [DK-40439] NR 46 TC 40 Z9 40 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1991 VL 32 IS 11 BP 1823 EP 1836 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR420 UT WOS:A1991GR42000011 PM 1770302 ER PT J AU STACPOOLE, PW VONBERGMANN, K KILGORE, LL ZECH, LA FISHER, WR AF STACPOOLE, PW VONBERGMANN, K KILGORE, LL ZECH, LA FISHER, WR TI NUTRITIONAL REGULATION OF CHOLESTEROL-SYNTHESIS AND APOLIPOPROTEIN-B KINETICS - STUDIES IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA AND NORMAL SUBJECTS TREATED WITH A HIGH-CARBOHYDRATE, LOW FAT DIET SO JOURNAL OF LIPID RESEARCH LA English DT Article DE LIPOPROTEIN KINETICS; STEROL BALANCE ID LOW-DENSITY-LIPOPROTEIN; DEPENDENT DIABETES-MELLITUS; HIGH-GLUCOSE DIET; RAT-LIVER; ACID SYNTHESIS; SATURATED-FAT; APOPROTEIN-B; LIPID-LEVELS; PLASMA; METABOLISM AB High carbohydrate, low fat diets decrease plasma low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) mass in normal subjects and in patients with familial hypercholesterolemia (FH). To investigate the mechanisms for these effects, four normal, four FH heterozygous, and one FH homozygous subjects were studied on a basal (45% carbohydrate. 40% fat) diet and during continuous nasogastric infusion of Vivonex (90% carbohydrate, 1% fat). For the entire group, the mean changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides were -90. -95, -14 (all P < 0.01) and +114 (P < 0.02) mg/dl, respectively. Fecal sterol balance measurements demonstrated a 24% decrease in whole body cholesterol synthesis in normals, from 8.4 +/- 4.4 (mean +/- SD) to 6.4 +/- 1.3 mg/kg per day and in FH subjects, a 58% decrease, from 11.4 +/- 5.6 to 4.8 +/- 1.7 mg/kg per day (both P < 0.05). ApoB kinetic studies were performed using a [H-3]leucine tracer in two normals and three FH heterozygotes on both basal and Vivonex regimens, and the results were analyzed by compartmental modeling using the SAAM program. Total apoB production was not altered in a consistent manner by carbohydrate feeding. ApoB secretion, however, was shifted from the production of small VLDL/IDL-like particles to large VLDL. by Vivonex, with an accompanying increase in intrahepatic assemblage time before secretion. In the two normal subjects, Vivonex induced an increase in apoB loss as VLDL/IDL; however, in the FH patients no such loss occurred. A decrease (P < 0.05) in the residence time of LDL-apoB occurred for all subjects and was the primary determinant of the fall in plasma LDL concentration, since LDL-apoB transport did not change consistently. (jlr) Thus, in FH patients, a high carbohydrate, low fat diet results in suppression of cholesterol synthesis and a fall in plasma LDL concentration due to an increased plasma clearance rate for LDL. C1 UNIV FLORIDA,COLL MED,DEPT PHARMACOL,GAINESVILLE,FL 32610. UNIV FLORIDA,COLL MED,DEPT BIOCHEM,GAINESVILLE,FL 32610. UNIV BONN,DEPT MED CLIN PHARMACOL,W-5300 BONN 1,GERMANY. NIH,MATH BIOL LAB,BETHESDA,MD 20892. RP STACPOOLE, PW (reprint author), UNIV FLORIDA,COLL MED,DEPT MED ENDOCRINOL & METAB,BOX J-226,GAINESVILLE,FL 32610, USA. FU NHLBI NIH HHS [HL29394, HL32550, HL27807] NR 58 TC 26 Z9 26 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1991 VL 32 IS 11 BP 1837 EP 1848 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR420 UT WOS:A1991GR42000012 PM 1770303 ER PT J AU RADER, DJ CASTRO, G ZECH, LA FRUCHART, JC BREWER, HB AF RADER, DJ CASTRO, G ZECH, LA FRUCHART, JC BREWER, HB TI INVIVO METABOLISM OF APOLIPOPROTEIN A-I ON HIGH-DENSITY-LIPOPROTEIN PARTICLES LPA-I AND LPA-I,A-II SO JOURNAL OF LIPID RESEARCH LA English DT Article DE CHOLESTEROL; KINETICS; IMMUNOAFFINITY; ATHEROSCLEROSIS ID CORONARY-ARTERY DISEASE; ISCHEMIC HEART-DISEASE; AMINO-ACID SEQUENCE; IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODY; CHOLESTEROL LEVELS; PLASMA-MEMBRANES; HEPATIC LIPASE; APOA-I; SUBCLASSES AB Apolipoprotein (apo) A-I is the major protein in high density lipoproteins (HDL) and is found in two major subclasses of lipoproteins, those containing apolipoprotein A-II (termed LpA-I,A-II) and those without apoA-II (termed LpA-I). The in vivo kinetics of apoA-I on LpA-I and LpA-I,A-II were investigated in normolipidemic human subjects. In the first series of studies, radiolabeled apoA-I and apoA-II were reassociated with autologous plasma lipoproteins and injected into normal subjects. LpA-I and LpA-I,A-II were isolated from plasma at selected time points by immunoaffinity chromatography. By 24 h after injection, only 52.8 +/- 1.0% of the apoA-I in LpA-I remained, whereas 66.9 +/- 2.7% of apoA-I in LpA-I,A-II remained (P < 0.01). In the second series of studies, purified apoA-I was labeled with either I-131 or I-125 and reassociated with autologous plasma. Isolated LpA-I and LpA-I,A-II particles differentially labeled with I-131-labeled apoA-I and I-125-labeled apoA-I, respectively, were simultaneously injected into study subjects. The plasma residence time of apoA-1 injected on LpA-I (mean 4.39 days) was substantially shorter than that of apoA-I injected on LpA-I,A-II (mean 5.17 days), with a mean difference in residence times of 0.79 +/- 0.08 days (P < 0.001). (jlr) These data demonstrate that apoA-I injected on LpA-I is catabolized more rapidly than apoA-I injected on LpA-I,A-II. The results are consistent with the concept that LpA-I and LpA-I,A-II have divergent metabolic pathways. C1 PASTEUR INST,INSERM,U325,LILLE,FRANCE. RP RADER, DJ (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 167 Z9 167 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1991 VL 32 IS 11 BP 1849 EP 1859 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GR420 UT WOS:A1991GR42000013 PM 1770304 ER PT J AU KNUTTEL, A BALABAN, RS AF KNUTTEL, A BALABAN, RS TI A NOVEL-APPROACH FOR THE DETERMINATION OF FAST EXCHANGE-RATES SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID CHEMICAL EXCHANGE; NMR-SPECTROSCOPY; ROTATING FRAME; RELAXATION RP KNUTTEL, A (reprint author), NIH,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON PD NOV PY 1991 VL 95 IS 2 BP 309 EP 319 DI 10.1016/0022-2364(91)90221-E PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA GN287 UT WOS:A1991GN28700009 ER PT J AU LEVY, E MARGALITH, M SAROV, B SAROV, I RINALDO, CR DETELS, R PHAIR, J KASLOW, R GINZBURG, H SAAH, AJ AF LEVY, E MARGALITH, M SAROV, B SAROV, I RINALDO, CR DETELS, R PHAIR, J KASLOW, R GINZBURG, H SAAH, AJ TI CYTOMEGALOVIRUS IGG AND IGA SERUM ANTIBODIES IN A STUDY OF HIV-INFECTION AND HIV RELATED DISEASES IN HOMOSEXUAL MEN SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE CMV; HIV; IGA; IGG; ANTIBODIES; HOMOSEXUALS ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; EPSTEIN-BARR-VIRUS; HTLV-III; AIDS; LYMPHOCYTES; PROGRESSION; EXPRESSION; ANTIGEN; PATIENT AB The significance of serum IgG and IgA antibodies to cytomegalovirus (CMV) at various stages of human immune deficiency virus (HIV) infection was studied in 175 homosexual men. Sera were obtained from 123 HIV seropositives [41 asymptomatic, 29 with lymphadenopathy associated syndrome (LAS), 22 with AIDS related complex (ARC), and 31 AIDS patients], 17 HIV seroconverters, and 35 HIV asymptomatic seronegatives. The sera were tested blindly for CMV IgA and IgG antibodies using the immunoperoxidase assay (IPA) and CMV infected human embryo cells. Cross-sectional analysis of CMV IgG antibodies at a titer of greater-than-or-equal-to 20 showed 87% and 100% prevalence in the HIV seronegative groups and in the HIV seropositive groups, respectively (P < 0.05). CMV IgG antibodies at a titer of greater-than-or-equal-to 80 were present in significantly higher proportions among the HIV seropositive subjects of the various groups as compared with the HIV seronegative homosexual men. However, in the HIV seronegatives who later seroconverted to HIV, a significantly higher prevalence of CMV antibodies (35%) was detected before HIV seroconversion, as compared with the persistently HIV seronegative subjects (14.3%) (P < 0.05). The HIV seronegatives pre-HIV seroconversion also exhibited a significantly higher geometric mean titer (GMT) of CMV IgG antibodies (62.17 +/- 0.64) as compared with the persistently HIV sero-negatives (34.0 +/- 0.6) (P = 0.03). Significantly higher GMTs of CMV IgG antibodies were detected in all the HIV seropositive groups as compared with the persistently HIV seronegative group. CMV IgG antibodies were not detected in the HIV seronegative subjects. CMV IgA antibodies were found in 5.9% of the HIV seroconverters, in 19.5% of the HIV seropositive asymptomatic subjects, 34.5% of LAS, 22.7% of ARC, and 6.5% of AIDS patients. These data support the concept that CMV might be associated with susceptibility of homosexual men to HIV infection and disease progression. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,VIROL UNIT,IL-84105 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,FAC HLTH SCI,EPIDEMIOL UNIT,IL-84105 BEER SHEVA,ISRAEL. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. NORTHWESTERN UNIV,SCH MED,HOWARD BROWN MEM CLIN,CHICAGO,IL 60611. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [N01-AI-72632, N01-AI-72634, N01-AI-72631] NR 42 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 1991 VL 35 IS 3 BP 174 EP 179 DI 10.1002/jmv.1890350306 PG 6 WC Virology SC Virology GA GN530 UT WOS:A1991GN53000005 PM 1666647 ER PT J AU MARAGOS, CM MORLEY, D WINK, DA DUNAMS, TM SAAVEDRA, JE HOFFMAN, A BOVE, AA ISAAC, L HRABIE, JA KEEFER, LK AF MARAGOS, CM MORLEY, D WINK, DA DUNAMS, TM SAAVEDRA, JE HOFFMAN, A BOVE, AA ISAAC, L HRABIE, JA KEEFER, LK TI COMPLEXES OF NO WITH NUCLEOPHILES AS AGENTS FOR THE CONTROLLED BIOLOGICAL RELEASE OF NITRIC-OXIDE - VASORELAXANT EFFECTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE RELAXATION; ORGANIC NITRATES; AQUEOUS-SOLUTION; TRIOXODINITRATE(II); NITROPRUSSIDE; DISSOCIATION; HEMOGLOBIN; MECHANISM AB Selected nucleophile/nitric oxide adducts [compounds which contain the anionic moiety, XN(O-)N = O] were studied for their ability to release nitric oxide spontaneously in aqueous solution and for possible vasoactivity. The diversity of structures chosen included those in which the nucleophile residue, X, was that of a secondary amine [Et2N, as in [Et2NN(N = O)O]Na, 1], a primary amine [iPrHN, as in [iPrHNN(N = O)O]Na, 2], a polyamine, spermine [as in the zwitterion H2N(CH2)3NH2+(CH2)4N[N(N = O)O-](CH2)3NH2, 3], oxide [as in Na[ON(N = O)O]Na, 4], and sulfite [as in NH4[O3SN(N = O)O]NH4, 5]. The rate constants (k) for decomposition in pH 7.4 phosphate buffer at 37-degrees-C, as measured by following loss of chromophore at 230-260 nm, were as follows: 1, 5.4 x 10(-3) s-1; 2, 5.1 X 10(-3) s-1; 3, 0.30 x 10(-3) s-1; 4, 5.0 x 10(-3) s-1; and 5, 1.7 x 10(-3) s-1. The corresponding extents of nitric oxide release (E(NO)) were 1.5, 0.73, 1.9, 0.54, and 0.001 mol/mol of starting material consumed, respectively, as determined from the integrated chemiluminescence response. Vasodilatory activities expressed as the concentrations required to induce 50% relaxation in norepinephrine-constricted aortic rings bathed in pH 7.4 buffer at 37-degrees-C (EC50) were as follows: 1, 0.19-mu-M; 2, 0.45-mu-M; 3, 6.2-mu-M; 4, 0.59-mu-M; and 5, 62-mu-M. Vasorelaxant potency (expressed as 1/EC50) was strongly correlated with the quantity of .NO calculated from the physicochemical data to be released in the interval required to achieve maximum relaxation at the EC50 doses (r = 0.995). This suggests that such nucleophile/.NO adducts might generally be useful as vehicles for the nonenzymatic generation of nitric oxide, in predictable amounts and at predictable rates, for biological purposes. The particular significance for possible drug design is underscored in the very favorable potency comparison between several of these agents and the established nitrovasodilators sodium nitroprusside and glyceryl trinitrate (EC50 values of 2.0 and > 10-mu-M, respectively) in parallel aortic ring tests. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. TEMPLE UNIV,DEPT MED,CARDIOL SECT,PHILADELPHIA,PA 19140. NATL HEART LUNG & BLOOD INST,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,DEPT PHARMACOL,CHICAGO,IL 60612. PRI DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74102] NR 49 TC 634 Z9 638 U1 4 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV PY 1991 VL 34 IS 11 BP 3242 EP 3247 DI 10.1021/jm00115a013 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GQ615 UT WOS:A1991GQ61500013 PM 1956043 ER PT J AU DRISCOLL, JS MARQUEZ, VE PLOWMAN, J LIU, PS KELLEY, JA BARCHI, JJ AF DRISCOLL, JS MARQUEZ, VE PLOWMAN, J LIU, PS KELLEY, JA BARCHI, JJ TI ANTITUMOR PROPERTIES OF 2(1H)-PYRIMIDINONE RIBOSIDE (ZEBULARINE) AND ITS FLUORINATED ANALOGS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEIC-ACID COMPONENTS; PYRIMIDIN-2-ONE NUCLEOSIDES; 2-PYRIMIDINONE NUCLEOSIDES; CYTIDINE DEAMINASE; ESCHERICHIA-COLI; HETEROCYCLES; DERIVATIVES; GLYCOSIDES AB 2(1H)-Pyrimidinone riboside (zebularine, 1b) and its 5-fluoro (6b) and 2'-ara-fluoro (7b) analogues have been synthesized and evaluated in vivo as antitumor agents. Zebularine provides increase in life span (ILS) values of ca. 70% against intraperitoneal (ip) murine B16 melanoma and 50% against P388 leukemia. This compound is active when administered either ip or orally against ip or subcutaneously implanted L1210 leukemia, producing ILS values of about 100% at an optimum dose of 400 mg/kg. 1b is also active (60% ILS) against ara-C-resistant L1210. The analogous unsubstituted purine riboside nebularine (2) has modest activity against P388 leukemia (60% ILS). While 2'-ara-fluorozebularine (7b) is only marginally active (40% ILS) at high doses against L1210 leukemia, 5-fluoro analogue 6b is more active than zebularine and is ca. 100 times more potent. Although the activity of 6b is about the same as that of 1b against P388 leukemia, greater potency also is realized in this model. Zebularine is a strong inhibitor of cytidine deaminase, but in contrast to tetrahydrouridine, 1b is acid-stable. In an attempt to use this property to advantage in oral administration, 1b and ara-C have been orally coadministered to mice with ip L1210 leukemia. When zebularine is given in divided doses, up to a 2-fold increase in activity is realized, relative to treatment with the same dose of ara-C alone. C1 NCI,DCT,DTP,PHARMACOL BRANCH,BETHESDA,MD 20892. RP DRISCOLL, JS (reprint author), NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014 NR 24 TC 56 Z9 58 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV PY 1991 VL 34 IS 11 BP 3280 EP 3284 DI 10.1021/jm00115a017 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GQ615 UT WOS:A1991GQ61500017 PM 1956046 ER PT J AU RINGEL, I JAFFE, D ALERHAND, S BOYE, O MUZAFFAR, A BROSSI, A AF RINGEL, I JAFFE, D ALERHAND, S BOYE, O MUZAFFAR, A BROSSI, A TI FLUORINATED COLCHICINOIDS - ANTITUBULIN AND CYTOTOXIC PROPERTIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; NATURAL COLCHICINOIDS; MICROTUBULE PROTEIN; METHYLTHIO ETHERS; TUBULIN COMPLEX; BINDING; THIOCOLCHICINE; SITE; 3-DEMETHYLTHIOCOLCHICINE; PODOPHYLLOTOXIN AB The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cell lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug-resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent. C1 NIDDK,NAT PROD SECT,BETHESDA,MD 20892. RP RINGEL, I (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT PHARMACOL,POB 1172,IL-91010 JERUSALEM,ISRAEL. NR 27 TC 27 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV PY 1991 VL 34 IS 11 BP 3334 EP 3338 DI 10.1021/jm00115a026 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GQ615 UT WOS:A1991GQ61500026 PM 1956052 ER PT J AU NARROW, WE AF NARROW, WE TI THE SCOPE OF EPIDEMIOLOGIC PSYCHIATRY - WILLIAMS,P, WILKINSON,G, RAWNSLEY,K SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP NARROW, WE (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1991 VL 179 IS 11 BP 706 EP 707 DI 10.1097/00005053-199111000-00019 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GP818 UT WOS:A1991GP81800019 ER PT J AU WINSLOW, JT AF WINSLOW, JT TI HOUSE MOUSE AGGRESSION - BRAIN,PF, MAINARDI,D, PARMIGIANI,S SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP WINSLOW, JT (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1991 VL 179 IS 11 BP 708 EP 708 DI 10.1097/00005053-199111000-00023 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GP818 UT WOS:A1991GP81800023 ER PT J AU WALDBILLIG, RJ PFEFFER, BA SCHOEN, TJ ADLER, AA SHENORR, Z SCAVO, L LEROITH, D CHADER, GJ AF WALDBILLIG, RJ PFEFFER, BA SCHOEN, TJ ADLER, AA SHENORR, Z SCAVO, L LEROITH, D CHADER, GJ TI EVIDENCE FOR AN INSULIN-LIKE GROWTH-FACTOR AUTOCRINE-PARACRINE SYSTEM IN THE RETINAL PHOTORECEPTOR-PIGMENT EPITHELIAL-CELL COMPLEX SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE INSULIN-LIKE GROWTH FACTOR; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN; INSULIN-LIKE GROWTH FACTOR RECEPTORS; INTERPHOTORECEPTOR MATRIX; RETINAL PIGMENT EPITHELIUM; O-LINKED AND N-LINKED GLYCOSYLATION ID FACTOR-BINDING-PROTEIN; N-ACETYLGLUCOSAMINIDASE-F; BOVINE NEURAL RETINA; ROD OUTER SEGMENTS; FACTOR-I; IGF-I; INTERPHOTORECEPTOR MATRIX; KINASE-ACTIVITY; ALPHA-SUBUNIT; RECEPTORS AB The interphotoreceptor matrix (IPM), lying between retinal photoreceptor and pigment epithelial (RPE) cells, contains insulin-like growth factor I(IGF-I) immunoreactivity that co-elutes with authentic human IGF-I in HPLC analyses. Cultured human RPE cells synthesize and release IGF-I, raising the possibility that the RPE serves as a source of IPM IGF-I in vivo. Photoreceptor rod outer segments and cultured monkey RPE cells express specific IGF-I receptors with alpha-subunits of 120 and 138 kDa, respectively. They thus appear to be of the "brain" (in photoreceptors) and "peripheral" (in RPE cells) receptor subtypes. Additionally, the IPM contains high levels of an IGF binding protein (IGF-BP) that specifically binds IGF-I and IGF-II. The IPM-BP is visualized as a single radiographic band by both ligand blot and affinity cross-linking procedures. With enzymes specific for removing N- and O-linked oligosaccharides, the IPM-BP was found to contain O- but not N-linked glycosylated side chains. The distinctive size and glycosylation pattern of the IPM-BP indicate that it is not derived from the vitreous or serum but instead is synthesized locally. The presence of IGF-I and IGF-BP in the IPM, together with the presence of IGF-I receptors on both photoreceptor and RPE cells, suggests the presence of an outer retina autocrine-paracrine system. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD. RETINA FDN,EYE RES INST,BOSTON,MA 02114. RP WALDBILLIG, RJ (reprint author), NEI,BLDG 6A,ROOM B1A-11,BETHESDA,MD 20892, USA. NR 55 TC 69 Z9 69 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1991 VL 57 IS 5 BP 1522 EP 1533 DI 10.1111/j.1471-4159.1991.tb06347.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GL288 UT WOS:A1991GL28800009 PM 1717648 ER PT J AU SMITH, CB SUN, Y DEIBLER, GE SOKOLOFF, L AF SMITH, CB SUN, Y DEIBLER, GE SOKOLOFF, L TI EFFECT OF LOADING DOSES OF L-VALINE ON RELATIVE CONTRIBUTIONS OF VALINE DERIVED FROM PROTEIN-DEGRADATION AND PLASMA TO THE PRECURSOR POOL FOR PROTEIN-SYNTHESIS IN RAT-BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CEREBRAL PROTEIN SYNTHESIS; AMINO ACID RECYCLING; AMINO ACID FLOODING; AMINOACYL-TRANSFER RNA ID COMPARTMENTATION; TURNOVER AB "Flooding" amino acid pools with high doses of labeled amino acids of low specific activity has been proposed to minimize the effects of recycling of amino acids derived from protein degradation on the specific activity of the amino acid precursor pool for protein synthesis. We have examined the influence of recycling on the precursor pool for protein synthesis under conditions in which plasma valine concentrations were normal (0.19 mM) and "flooded" (10-28 mM) by comparing the steady-state specific activity of the tRNA-bound valine with that of the plasma valine. Under normal and "flooding" conditions, the relative contributions of valine from protein degradation to the precursor pool were 63 and 26%, respectively; "flooding" with a plasma level of 28 mM raised the brain acid-soluble pool level to 3.1 mM but was no more effective in decreasing the relative contribution of valine from protein degradation to the precursor pool than "flooding" with a plasma level of 17 mM valine, which raised the brain acid-soluble level only to 2.3 mM. The results of these studies show that "flooding" amino acid pools does indeed reduce the effect of recycling on the precursor amino acid pool for protein synthesis, but it does not totally eliminate it. RP SMITH, CB (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1991 VL 57 IS 5 BP 1540 EP 1547 DI 10.1111/j.1471-4159.1991.tb06349.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GL288 UT WOS:A1991GL28800011 PM 1919572 ER PT J AU GREWAL, RP PETRONAS, N BARTON, NW AF GREWAL, RP PETRONAS, N BARTON, NW TI LATE ONSET GLOBOID-CELL LEUKODYSTROPHY SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Note ID LEUCODYSTROPHY; DISEASE AB A 29 year old male with onset of globoid cell leukodystrophy at age 14 is described. This is the first case of enzymatically confirmed globoid cell leukodystrophy with onset of symptoms after the age of ten. This patient is unique because of the late onset and slow progression and extends the clinical spectrum of globoid cell leukodystrophy. C1 NINCDS,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RP GREWAL, RP (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,RM 3D03,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1991 VL 54 IS 11 BP 1011 EP 1012 DI 10.1136/jnnp.54.11.1011 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA GP509 UT WOS:A1991GP50900019 PM 1800646 ER PT J AU WAITZMAN, DM MA, TP OPTICAN, LM WURTZ, RH AF WAITZMAN, DM MA, TP OPTICAN, LM WURTZ, RH TI SUPERIOR COLLICULUS NEURONS MEDIATE THE DYNAMIC CHARACTERISTICS OF SACCADES SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ALERT RHESUS-MONKEY; EYE-MOVEMENTS; SINGLE UNITS; RETICULAR-FORMATION; LOCAL FEEDBACK; FIELDS; STIMULATION; GENERATOR; VELOCITY; PATTERNS AB 1. The locus of activity within the superior colliculus (SC) is related to the desired displacement of the eye. Current hypotheses suggest that the location of this locus of activity determines the amplitude of the saccade and that the level of activity at this locus determines eye velocity. We present evidence that suggests that, although the locus determines the amplitude of the saccade, the level of activity in the colliculus encodes dynamic motor error (the difference between desired and current eye displacement). 2. We categorized 86 neurons in the intermediate and deep layers of the superior colliculus of two rhesus monkeys by their activity in relation to the end of saccadic eye movements. In 36% of the cells (n = 31), activity was completely cut off by the end of the saccade (clipped cells). For 53% of cells (n = 46), the major burst of activity ceased by the end of the saccade, but activity continued for 30-100 ms after the end of the movement (partially clipped cells). The remaining 10% of the cells (n = 9) had no clear burst of activity (unclipped cells) but rather had activity that increased gradually before the saccade and then slowly decreased for up to 100 ms after the saccade. These categories were part of a continuum of cell types rather than discrete classes of cells. 3. We first determined whether this new categorization of cells revealed a special relation between the discharge of clipped and partially clipped cells and saccadic amplitude and peak velocity. As expected, we found a steady increase in spike count as saccadic amplitude increased up to the center of the movement field, and an increase in peak spike discharge as peak velocity increased up to a maximum radial eye velocity. Variability in the cell discharge was substantially greater than the variability of saccadic amplitude or peak velocity. We concluded that these single point or averaged measures did not reveal any new functional relationship of these cells. 4. We then examined the relationship of the temporal pattern of discharge of clipped and partially clipped cells to instantaneous changes in radial error and radial velocity. There was a monotonic decay in spike discharge with declining radial error. In contrast, there was a complex, multivalued relationship between spike discharge and radial velocity; collicular cells produced two different values of spike discharge for the same velocity, one during acceleration and the other during deceleration of the eye during a saccade. When saccadic duration and cell discharge were normalized within groups of clipped and partially clipped cells of the same amplitude range, these relationships of radial error and radial velocity to spike discharge were maintained. 5. When all amplitude groups were normalized and averaged together, the relationship of radial error to spike discharge remained very close to linear. However, the complex, multivalued relationship of radial velocity to spike discharge became much closer to single valued, because cells whose discharge either led or lagged the changes in velocity were averaged together. 6. On the basis of these observations, we propose a collicular feedback model of the saccadic system that places the SC inside the feedback loop controlling saccadic amplitude. This model can account for the dynamic relationships of collicular firing to both saccadic amplitude and velocity. It also provides insight into previous experiments showing that a change in the level of activity in the SC can change saccadic velocity. Our model shows explicitly how the superior colliculus participates in transforming the spatial locus of collicular activity into the rate of discharge needed to innervate eye muscles (the spatial-to-temporal transformation). C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. FU NEI NIH HHS [F32-EY-05950] NR 49 TC 183 Z9 183 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1991 VL 66 IS 5 BP 1716 EP 1737 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GP882 UT WOS:A1991GP88200022 PM 1765803 ER PT J AU BONDY, CA AF BONDY, CA TI TRANSIENT IGF-I GENE-EXPRESSION DURING THE MATURATION OF FUNCTIONALLY RELATED CENTRAL PROJECTION NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GROWTH FACTOR-I; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; INSITU HYBRIDIZATION; PROGENITOR CELLS; RECEPTOR GENE; INSULIN; LOCALIZATION; SOMATOMEDINS; SURVIVAL AB Insulin-like growth factor I (IGF-I) is a monomeric peptide with significant homology to proinsulin. IGF-I has a number of potent effects on cultured neural tissue, including the stimulation of mitosis in sympathetic neuroblasts; the promotion of neurite outgrowth in cortical, sensory, and sympathetic neurons; and the induction of oligodendrocyte differentiation. In order to determine the sites in which IGF-I may play a role in neural development in vivo, the pattern of IGF-I gene expression in the developing rat brain has been analyzed by means of in situ hybridization histochemistry. Transient IGF-I gene expression is seen during the maturation of specific groups of functionally related sensory and cerebellar projection neurons. IGF-I mRNA is abundant within developing cerebellar Purkinje cells and in the major cerebellar relay centers, including the inferior olive, medial vestibular and lateral reticular nuclei of the brainstem, and the deep cerebellar and red nuclei. Similarly, IGF-I mRNA is localized in the synaptic stations of the developing olfactory, auditory, visual, and somatosensory systems. For example, in the auditory system, IGF-I mRNA is abundant in the cochlear nucleus, superior olive, lateral lemniscus, medial geniculate body, and inferior colliculus. In each system, IGF-I gene expression is found predominantly in long-axon projection neurons, appearing during a relatively late stage in their development, at a time of maturation of dendrites and synapse formation. The specific timing and selective localization of neuronal IGF-I gene expression described in this study suggest that IGF-I may have a role in the shaping of system-specific synaptic connections or myelinization. RP BONDY, CA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 40 TC 247 Z9 250 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV PY 1991 VL 11 IS 11 BP 3442 EP 3455 PG 14 WC Neurosciences SC Neurosciences & Neurology GA GP898 UT WOS:A1991GP89800013 PM 1658250 ER PT J AU VAUGHAN, RA SIMANTOV, R LEW, R KUHAR, MJ AF VAUGHAN, RA SIMANTOV, R LEW, R KUHAR, MJ TI A RAPID BINDING ASSAY FOR SOLUBILIZED DOPAMINE TRANSPORTERS USING [H-3] WIN 35,428 SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE DOG CAUDATE NUCLEUS; COCAINE RECEPTOR ID COCAINE RECEPTORS AB The cocaine analog [H-3]WIN 35,428 was used to label digitonin-solubilized dopamine transporters from dog caudate nucleus. The assay consists of incubation of extracts with the ligand followed by separation of free from bound ligand by centrifugation after adding activated charcoal. Specific binding was observed in dog caudate but was absent in dog cerebellar extracts. Binding was linear with tissue, saturable, and of high affinity (K(d) = 16 nM). In competition studies, soluble [H-3]WIN 35,428 binding was inhibited strongly by mazindol, GBR 12909, and (-)-cocaine but only weakly by citalopram, desipramine, and (+)-cocaine; this is typical of binding to the dopamine transporter. Compared to assays using [H-3]GBR 12935, (-)-cocaine was relatively more potent, suggesting that the cocaine and GBR 12935 binding sites are somewhat different. When soluble extract was chromatographed on a wheat germ agglutinin-Sepharose column, [H-3]WIN 35,428 binding activity was eluted with N-acetylglucosamine in a manner similar to photoaffinity-labeled dopamine transporters. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BLDG C,BALTIMORE,MD 21224. NR 12 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1991 VL 40 IS 1 BP 9 EP 16 DI 10.1016/0165-0270(91)90112-D PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GW876 UT WOS:A1991GW87600002 PM 1795555 ER PT J AU ZORAD, S ALSASUA, A SAAVEDRA, JM AF ZORAD, S ALSASUA, A SAAVEDRA, JM TI A MODIFIED QUANTITATIVE AUTORADIOGRAPHIC ASSAY FOR ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS IN RAT-BRAIN SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE ATRIAL MATRIURETIC PEPTIDE; AUTORADIOGRAPHY; PROTEINASE INHIBITORS; RAT BRAIN ID CHOROID-PLEXUS; BINDING-SITES; HYPERTENSIVE RATS; LOCALIZATION; INCREASES; SUBTYPES; CELLS; ANF AB New conditions for quantitative autoradiographic determination of natriuretic peptide (ANP) binding in rat brain were developed in order to inhibit hormone degradation during incubation without the use of proteinase inhibitors. This procedure includes 1-h preincubation of tissue slices in hypotonic buffer and incubation at 4-degrees-C in the presence of 4% proteinase-free albumin. ANP binding to choroid plexus and subfornical organ under above conditions reached equilibrium after 90 min. ANP degradation at the end of the incubation did not exceed 2%. Binding data analysis revealed the previously undetected presence of two distinct ANP binding sites in the rat choroid plexus. RP ZORAD, S (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1991 VL 40 IS 1 BP 63 EP 69 DI 10.1016/0165-0270(91)90117-I PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GW876 UT WOS:A1991GW87600007 PM 1665530 ER PT J AU WOLFF, A SCOTT, J WOODS, K FOX, PC AF WOLFF, A SCOTT, J WOODS, K FOX, PC TI AN INVESTIGATION OF PAROTID-GLAND FUNCTION AND HISTOPATHOLOGY IN AUTOIMMUNE DISEASE-PRONE MICE OF DIFFERENT AGE-GROUPS SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE AUTOIMMUNE DISEASE; HISTOPATHOLOGY; MOUSE; PAROTID; SALIVA; SJOGRENS SYNDROME ID SJOGRENS-SYNDROME; IMMUNOHISTOCHEMICAL CHARACTERIZATION; MOUSE; SIALADENITIS AB This work aimed to characterize parotid gland function in autoimmune disease-prone murine strains (MRL/n, MRL/1 and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/1 mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjogren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age. C1 NIDR,CLIN INVEST SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892. UNIV LIVERPOOL,ORAL PATHOL & MICROBIOL UNIT,LIVERPOOL L69 3BX,ENGLAND. NR 16 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD NOV PY 1991 VL 20 IS 10 BP 486 EP 489 DI 10.1111/j.1600-0714.1991.tb00409.x PG 4 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA GT033 UT WOS:A1991GT03300006 PM 1753352 ER PT J AU BRESLOW, RA HALLFRISCH, J GOLDBERG, AP AF BRESLOW, RA HALLFRISCH, J GOLDBERG, AP TI MALNUTRITION IN TUBEFED NURSING-HOME PATIENTS WITH PRESSURE SORES SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID POPULATION; NUTRITION; ZINC; MEN AB This study compares the nutritional status and dietary intake of 14 tubefed nursing home patients with pressure sores (age: 70 +/- 5 years, mean +/- SEM) to 12 tubefed patient-controls without sores (age: 60 +/- 7 years). Patients tended to have higher calorie intake (32 +/- 3 kcal/kg) than patient-controls (26 +/- 2 kcal/kg, p = 0.11). Protein intake was significantly higher in patients (1.4 +/- 0.2 g/kg) than patient-controls (0.9 +/- 0.1 g of protein per kg, p < 0.05). Despite increased calorie and protein intake, biochemical measures of nutritional status were worse in the patients. Serum albumin was lower in patients (33 +/- 1 g/L) than in patient-controls (37 +/- 1 g/L, p < 0.05) as was level of hemoglobin (patients: 117 +/- 5; patient-controls: 132 +/- 5 g/L, p < 0.05). Patients with stage IV (severe) sores had lower serum cholesterol levels (3.46 +/- 0.31 mmol/L, n = 5) than patients with stage II/III (milder) sores (4.58 +/- 0.23 mmol/L, n = 9, p < 0.05). Plasma zinc was low in both patients (11.2 +/- 0.6-mu-mol/L) and patient-controls (11.5 +/- 0.7-mu-mol/L, p = NS). Pressure sore surface area was positively correlated with calorie intake per kilogram of body weight (r = +0.59, p < 0.04) and negatively correlated with body mass index (r = -0.70, p < 0.03), hemoglobin (r = -0.55, p < 0.07) and serum cholesterol (r = -0.57, p < 0.05). Thus, tubefed nursing home patients with pressure sores are malnourished despite receiving a diet high in calories and protein. Their low body weight, hypoalbuminemia, anemia, and hypocholesterolemia suggest greatly increased requirements for calories and protein. Because most of the patients in this malnourished, chronically ill population tolerated tubefeeding well, increased provision of calories and protein via the enteral route seems a potentially achievable goal. C1 FRANCIS SCOTT KEY MED CTR,DEPT MED,DIV GERIAT,BALTIMORE,MD. NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,METAB SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD. RP BRESLOW, RA (reprint author), UNIV MARYLAND,DEPT HUMAN NUTR & FOOD SYST,COLLEGE PK,MD 20742, USA. FU NCRR NIH HHS [MO1-RR02719-04]; NIA NIH HHS [P01-AG04402-06] NR 37 TC 40 Z9 40 U1 0 U2 2 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 1991 VL 15 IS 6 BP 663 EP 668 DI 10.1177/0148607191015006663 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GP145 UT WOS:A1991GP14500014 PM 1766057 ER PT J AU PIZZO, PA RUBIN, M FREIFELD, A WALSH, TJ AF PIZZO, PA RUBIN, M FREIFELD, A WALSH, TJ TI THE CHILD WITH CANCER AND INFECTION .1. EMPIRIC THERAPY FOR FEVER AND NEUTROPENIA, AND PREVENTIVE STRATEGIES SO JOURNAL OF PEDIATRICS LA English DT Review ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; CLOSTRIDIUM-DIFFICILE INFECTION; PEDIATRIC ONCOLOGY PATIENTS; CYTOMEGALO-VIRUS INFECTION; BETA-LACTAM ANTIBIOTICS; ACUTE-LEUKEMIA; IMMUNOCOMPROMISED PATIENTS; RANDOMIZED TRIAL; DOUBLE-BLIND RP PIZZO, PA (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NR 112 TC 104 Z9 108 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 NOV PY 1991 VL 119 IS 5 BP 679 EP 694 DI 10.1016/S0022-3476(05)80281-1 PG 16 WC Pediatrics SC Pediatrics GA GN296 UT WOS:A1991GN29600001 PM 1941374 ER PT J AU SU, TP WU, XZ CONE, EJ SHUKLA, K GUND, TM DODGE, AL PARISH, DW AF SU, TP WU, XZ CONE, EJ SHUKLA, K GUND, TM DODGE, AL PARISH, DW TI SIGMA-COMPOUNDS DERIVED FROM PHENCYCLIDINE - IDENTIFICATION OF PRE-084, A NEW, SELECTIVE SIGMA-LIGAND SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; CENTRAL NERVOUS-SYSTEM; BINDING-SITES; ANTIPSYCHOTIC-DRUGS; RAT-BRAIN; MYENTERIC PLEXUS; RECEPTOR-SITES; HALOPERIDOL; SKF-10,047; PITUITARY AB A series of compounds derived from phencyclidine (PCP) was examined in the sigma-receptor and PCP receptor binding assays. The derivatives included compounds containing methylene, ethylene or carboxyl ethylene insertion between the cycloalkyl ring and the amine group of PCP. Various phenyl substitutions, cycloalkyl rings and amines of these derivatives were also examined. The methylene and ethylene insertions decreased the compounds' potencies at PCP receptors, whereas they increased the potencies at sigma-receptors. The carboxyl ethylene insertion produced compounds with negligible potencies at PCP receptors while possessing high potencies for sigma-receptors. One derivative (PRE-084; 2-(4-morpholino)ethyl 1-phenylcyclohexane-1-carboxylate hydrochloride) had an IC50 of 44 nM in the sigma-receptor assay, an IC50 of more than 100,000 nM for PCP receptors and an IC50 higher than 10,000 nM in a variety of other receptor systems. In general, compounds with hydroxy-substituted phenyl groups tended to have decreased potency at sigma-receptors, whereas methylphenyl and chlorophenyl substitutions increased potencies. Reduction of cycloalkyl ring size decreased potencies for sigma-receptors and quaternized amine groups invariably lowered the compound's potencies. Conformational analysis indicated that PRE-084 fitted onto a pharmacophore model for the sigma-ligands. The study describes a new, highly selective ligand for the sigma-receptor. The results of this study also confirm distinctly different structural requirements for binding to sigma and PCP receptors and provide a new structural consideration for synthesizing sigma-selective compounds. C1 NEW JERSEY INST TECHNOL,DEPT CHEM CHEM ENGN & ENVIRONM SCI,NEWARK,NJ 07102. SRI INT,DIV LIFE SCI,BIOORGAN CHEM LAB,MENLO PK,CA 94025. RP SU, TP (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 43 TC 57 Z9 58 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1991 VL 259 IS 2 BP 543 EP 550 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GP823 UT WOS:A1991GP82300011 PM 1658302 ER PT J AU DROWER, EJ STAPELFELD, A RAFFERTY, MF DECOSTA, BR RICE, KC HAMMOND, DL AF DROWER, EJ STAPELFELD, A RAFFERTY, MF DECOSTA, BR RICE, KC HAMMOND, DL TI SELECTIVE ANTAGONISM BY NALTRINDOLE OF THE ANTINOCICEPTIVE EFFECTS OF THE DELTA-OPIOID AGONIST CYCLIC[D-PENICILLAMINE(2)-D-PENICILLAMINE(5)]ENKEPHALIN IN THE RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MU-MEDIATED ANTINOCICEPTION; MESSAGE ADDRESS CONCEPT; RECEPTOR ANTAGONISTS; CROSS-TOLERANCE; INVIVO EVIDENCE; SPINAL-CORD; MOUSE; ANALGESIA; MORPHINE; MICE AB Spinal delta opioid receptors have been proposed to mediate antinociception in the rat on the basis of 1) the efficacy of a small number of agonists; 2) the lack of effect of mu-selective antagonists; and 3) the lack of cross-tolerance with mu-selective agonists. However, direct evidence to support or refute this postulate has not been obtained in the rat due to a lack of suitable delta-selective antagonists. The present study characterized the ability of Naltrindole (NTI, 17-cyclopropylmethyl-6,7-dehydro-4,5-alpha-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan), a recently discovered delta-selective antagonist, to antagonize the antinociception produced by intrathecal (i.t.) administration of the prototypic delta-selective agonist cyclic[D-penicillamine2-D-penicillamine5]enkephalin (DPDPE) or the mu-selective agonists morphine and [D-Ala2,MePhe4,Gly-ol5] enkephalin (DAMGO) in the rat. Intrathecal coadministration of NTI with DPDPE significantly antagonized the increase in tail-flick latency (TFL) and hot-plate latency (HPL) produced by DPDPE. In the absence of NTI, the ED50 values and 95% CL of DPDPE in the tail-flick and hot-plate tests were 2.8 (1.1-4.7) and 19.5 (13.3-33.7)-mu-g, respectively. In the presence of 10-mu-g of NTI, the ED50 value of DPDPE in the tail-flick test was unchanged and was increased by 2-fold in the hot-plate test to 35.9 (26.2-60.1)-mu-g. In the presence of 30-mu-g of NTI, the ED50 value of DPDPE in the tail-flick test was increased by 5-fold to 14.5 (8.5-24.9)-mu-g and its antinociceptive effect in the hot-plate test was antagonized completely. In contrast, 30-mu-g of i.t. NTI did not antagonize the increase in either TFL or HPL produced by i.t. administration of equieffective doses of the mu-selective agonists, morphine or DAMGO. The apparent pA2 value of NTI, determined using the time-dependent method of analysis, was 7.8 and its half-life was 12.5 min. Further characterization of NTI was not possible because higher doses (e.g., 60-mu-g i.t.) produced hindlimb paralysis or flaccidity. NTI was also an effective antagonist following systemic administration. Pretreatment with either 10 or 30 mg/kg s.c. of NTI significantly attenuated the increase in TFL and HPL produced by i.t. administration of DPDPE, but not that produced by i.t. administration of an equieffective dose of the mu-selective agonist DAMGO. These data provide direct evidence that the antinociception produced by i.t. administration of DPDPE is mediated by delta opioid receptors in the spinal cord, and provide further evidence for the selectivity of NTI as a delta opioid antagonist. C1 GD SEARLE & CO,DEPT CENT NERVOUS SYST RES,SKOKIE,IL 60077. NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV CHICAGO,DEPT ANAESTHESIA & CRIT CARE,CHICAGO,IL 60637. OI Hammond, Donna/0000-0002-2537-0441 NR 37 TC 76 Z9 76 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1991 VL 259 IS 2 BP 725 EP 731 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GP823 UT WOS:A1991GP82300038 PM 1658309 ER PT J AU KATAYAMA, Y WIDDICOMBE, JH AF KATAYAMA, Y WIDDICOMBE, JH TI HALIDE TRANSPORT IN XENOPUS OOCYTES SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MEMBRANE CHLORIDE CONDUCTANCE; CANINE TRACHEAL EPITHELIUM; CYSTIC-FIBROSIS; ION CHANNELS; CALCIUM; CELLS; PERMEABILITY; EXPRESSION; PROTEINS; ACIDS AB 1. Radioisotopes and intracellular microelectrodes were used to characterize the permeability of Xenopus oocytes to chloride and other halides. 2. Uptake of Cl-36 had a half-time for equilibration of approximation 3 h, with an initial rate of Cl- entry corresponding to a permeability coefficient of 3.9 x 10(-7) cm/s, and an equilibrium uptake of Cl-36 of 33 mM. 3. Replacement of bathing Na+ by K+ depolarized the oocytes from - 46 to -7 mV and stimulated influx approximately 3-fold. 4. Influx was linearly dependent on bathing [Cl-] and was temperature dependent with an activation energy of 46 kJ/mol. Influx of I-125 or Cl-36 was not affected by the presence of equal concentrations of other halides or thiocyanate. These results are consistent with a channel-mediated entry mechanism. 5. Diphenylamine-2-carboxylate (DPAC) and 9-anthracene carboxylate (9-AC), blockers of Cl- channels in other cells, inhibited Cl- entry with dissociation constants (K(d)s) of approximately 5 x 10(-4) and approximately 10(-3) M, respectively. Inhibitors of Cl- -HCO3- exchange or Na+-K+-2Cl- co-transport did not affect Cl- influx. 6. Attempts to lower or raise intracellular Ca2+ with BAPTA or A23187, respectively, were also without effect on Cl- influx. 7. The halide selectivity sequence determined with isotopes was I- (3.2) > Br-(1.3) > Cl- (1.0). However, DPAC inhibited almost all of the Cl-36 influx but only a small fraction of I-126 influx. 8. Replacement of bathing Cl- by I- or Br- resulted in hyperpolarizations, from which the same selectivity sequence was determined. 9. Replacement of bathing Cl- by gluconate caused a marked depolarization, which was inhibited by DPAC and, less potently, by 9-AC. C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP KATAYAMA, Y (reprint author), UNIV CALIF SAN FRANCISCO,NIH,CYST FIBROSIS RES CTR,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143, USA. FU NHLBI NIH HHS [HL 42368] NR 27 TC 15 Z9 15 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 1991 VL 443 BP 587 EP 599 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GP701 UT WOS:A1991GP70100035 PM 1822540 ER EF