FN Thomson Reuters Web of Science™ VR 1.0 PT J AU HOFMANN, GE SCOTT, RT HOROWITZ, GM THIE, J NAVOT, D AF HOFMANN, GE SCOTT, RT HOROWITZ, GM THIE, J NAVOT, D TI EVALUATION OF THE REPRODUCTIVE-PERFORMANCE OF WOMEN WITH ELEVATED DAY-10 PROGESTERONE LEVELS DURING OVARIAN RESERVE SCREENING SO FERTILITY AND STERILITY LA English DT Article DE OVARIAN RESERVE SCREENING; ELEVATED P LEVELS; PREGNANCY POTENTIAL ID FOLLICLE-STIMULATING-HORMONE; INVITRO FERTILIZATION; CLOMIPHENE CITRATE; LUTEINIZING-HORMONE; LEUPROLIDE ACETATE; CHRONOLOGICAL AGE; MENSTRUAL-CYCLE; BASAL; LIFE AB Objectives: To evaluate the relationship of elevated day 10 P levels (greater than or equal to 1.1 ng/mL, conversion factor to SI unit, 3.18) during ovarian reserve screening and reproductive performance. Design: Prospective screening with longitudinal follow-up. Interventions: One hundred seven women underwent ovarian reserve screening with a clomiphene citrate challenge test. Main Outcome Measures: Serum FSH, LH, and E(2) levels were determined on cycle day 3 and FSH, LH, and P levels were determined on day Ib. A fertility evaluation was completed and a treatment plan was instituted. Results: Twenty-two of 107 (20.6%) women had day 10 P levels greater than or equal to 1.1 ng/mL. Women with elevated day 10 P levels were similar in age to women with normal day 10 P levels (less than or equal to 0.9 ng/ mt) but had significantly shorter menstrual cycles, higher day 3 and day 10 FSH levels, higher day 3 E(2) levels, and higher day 10 LH levels than women with normal day 10 P levels. During ovarian hyperstimulation, women with elevated day 10 P levels required more ampules of hMG, had lower peak E(2) levels, and had fewer mature follicles than women with a normal day 10 P level. Sixteen of 85 (18.8%) women with normal day 10 P levels became pregnant, but none of the 22 women with elevated day 10 P levels became pregnant. The incidence of diminished ovarian reserve was higher in women with elevated day 10 P levels (13/22; 59%) when compared with women with a normal day 10 P levels (9/85; 10.6%). Conclusions: Elevated day 10 P levels (greater than or equal to 1.1 ng/mL) during ovarian reserve screening is associated with diminished ovarian reserve and correlates with menstrual cycle parameters associated with a short follicular phase and poor reproductive performance. C1 NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT OBSTET & GYNECOL,BETHESDA,MD 20814. NEW YORK MED COLL,DEPT OBSTET & GYNECOL,VALHALLA,NY 10595. RP HOFMANN, GE (reprint author), BETHESDA HOSP,BETHESDA CTR REPROD HLTH & FERTIL,DEPT OBSTET & GYNECOL,619 OAK ST,CINCINNATI,OH 45206, USA. NR 19 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1995 VL 63 IS 5 BP 979 EP 983 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA QU340 UT WOS:A1995QU34000006 PM 7720942 ER PT J AU HART, RW KEENAN, K TURTURRO, A ABDO, KM LEAKEY, J LYNCOOK, B AF HART, RW KEENAN, K TURTURRO, A ABDO, KM LEAKEY, J LYNCOOK, B TI CALORIC RESTRICTION AND TOXICITY SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID DRUG-METABOLIZING-ENZYMES; MALE FISCHER-344 RAT; GLUCOCORTICOID REGULATION; FOOD RESTRICTION; CYTOCHROME-P-450; CANCER; SYSTEM; GENE AB The modulatory effects of caloric intake on the rate and extent of both spontaneous and induced disease incidence is well known, but the significance of these effects in the interpretation of testing data has only recently become appreciated. This is especially true relative to the impact of caloric intake on both survival and background incidence for common tumors. In order to enhance the health and survival of animals ongoing chronic toxicity testing it has been suggested that such tests should restrict food consumption. Although this restriction will result in increasing survival of the test animals, it may also effect the expression of toxicity by altering agent metabolism and disease progression. Focus in this symposium is on the necessity to control dietary consumption in toxicity tests (dietary control), and if such a need does exist to what level of consumption should be diet be focused (caloric restriction). C1 MERCK & CO INC,W POINT,PA 19486. NIEHS,RES TRIANGLE PK,NC 27709. RP HART, RW (reprint author), NATL CTR TOXICOL RES,3900 NCTR DR,JEFFERSON,AR 72079, USA. NR 52 TC 57 Z9 58 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1995 VL 25 IS 2 BP 184 EP 195 DI 10.1006/faat.1995.1054 PG 12 WC Toxicology SC Toxicology GA QY808 UT WOS:A1995QY80800003 PM 7665002 ER PT J AU KANDASAMY, SB THIAGARAJAN, AB HARRIS, AH AF KANDASAMY, SB THIAGARAJAN, AB HARRIS, AH TI POSSIBLE INVOLVEMENT OF PROSTAGLANDINS IN INCREASES IN RAT PLASMA ADRENOCORTICOTROPIC HORMONE AND CORTICOSTERONE LEVELS INDUCED BY RADIATION AND INTERLEUKIN-1-ALPHA ALONE OR COMBINED SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; IMMUNE-RESPONSE; ACTH RELEASE; SECRETION; BRAIN; HYPOTHALAMUS; RECEPTORS; HYPERTHERMIA; IRRADIATION AB Exposing rats to 1-10 Gy of ionizing radiation increased plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, In both irradiated and nonirradiated rats, recombinant human interleukin-1 alpha (rhIL-1 alpha; 1 hr before radiation/sham exposure) enhanced plasma ACTH and CORT levels, Indomethacin, a cyclooxygenase inhibitor, attenuated plasma ACTH and CORT levels induced by radiation, Indomethacin also attenuated ACTH and CORT levels induced by radiation and interleukin-1 alpha alone or combined, These results suggest that prostaglandins are involved in the increase in plasma ACTH and CORT levels induced by radiation and rhIL-1 alpha alone or combined. (C) 1995 Society of Toxicology. C1 NIAAA,NEUROCHEM SECT,BETHESDA,MD 20892. RP KANDASAMY, SB (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT BEHAV SCI,BETHESDA,MD 20889, USA. NR 43 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1995 VL 25 IS 2 BP 196 EP 200 DI 10.1006/faat.1995.1055 PG 5 WC Toxicology SC Toxicology GA QY808 UT WOS:A1995QY80800004 PM 7665003 ER PT J AU IRWIN, RD HASEMAN, JK EUSTIS, SL AF IRWIN, RD HASEMAN, JK EUSTIS, SL TI 1,2,3-TRICHLOROPROPANE - A MULTISITE CARCINOGEN IN RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID SALMONELLA MUTAGENICITY; DISPOSITION; CHEMICALS; TESTS AB 1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0, 6, 20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females. (C) 1995 Society of Toxicology. RP IRWIN, RD (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1995 VL 25 IS 2 BP 241 EP 252 DI 10.1006/faat.1995.1060 PG 12 WC Toxicology SC Toxicology GA QY808 UT WOS:A1995QY80800009 PM 7665008 ER PT J AU LISZIEWICZ, J SUN, D LISZIEWICZ, A GALLO, RC AF LISZIEWICZ, J SUN, D LISZIEWICZ, A GALLO, RC TI ANTITAT GENE-THERAPY - A CANDIDATE FOR LATE-STAGE AIDS PATIENTS SO GENE THERAPY LA English DT Article DE TAT; TAR; HIV-1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; TAT PROTEIN; RETROVIRAL VECTOR; CELL-GROWTH; EXPRESSION; HIV; INFECTION AB Antitat is an autoregulated gene expressing an inhibitory RNA with dual function: if sequesters the Tat protein by polymeric-TAR and blocks the translation of the Tar messenger RNA by antisense-Tat. Using human T cell lines and peripheral blood lymphocytes as the in vitro target, we have previously: shown that antitat is an effective long-term suppressor of HIV-1, including 'field' isolates. To assess the efficacy of this,inhibitory gene better in the setting of an infected individual with late-stage AIDS, we examined its antiviral activity in an in vivo established infection. Peripheral blood mononuclear cells from AIDS patients were transduced with replication defective retroviral vectors carrying the antitat gene, in the absence of cell selection, the antitat gene blocked virus replication and allowed infected CD4(+) T cells to expand in culture. These results suggest that antitat gene therapy may be beneficial to block HIV-I replication and reconstitute the immune system oi late-phase AIDS patients. We introduced a new parameter, CRF, which defines the effectiveness of the ex vivo gene therapy treatment of AIDS patients. Antitat treatment was efficient in cells of ail patients regardless oi viral quasispecies, however, it was most potent in severely immunocompromised individuals. C1 LISZAPT GMBH,GOTTINGEN,GERMANY. RP LISZIEWICZ, J (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 23 TC 44 Z9 46 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1995 VL 2 IS 3 BP 218 EP 222 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA QW695 UT WOS:A1995QW69500008 PM 7614253 ER PT J AU YAMADA, H SASAKI, M HONDA, T WAKE, N BOYD, J OSHIMURA, M BARRETT, JC AF YAMADA, H SASAKI, M HONDA, T WAKE, N BOYD, J OSHIMURA, M BARRETT, JC TI SUPPRESSION OF ENDOMETRIAL CARCINOMA CELL TUMORIGENICITY BY HUMAN-CHROMOSOME-18 SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE-MUTATIONS; DCC; EXPRESSION; UTERUS; P53 AB Presumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome 18 is commonly seen in endometrial carcinoma, and the DCC gene on chromosome arm 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possibly DCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome 18 tagged with the pSV2-neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418-resistant microcell hybrids containing an extra copy of chromosome 18 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the Ishikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome 18 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene. (C) 1995 Wiley-Liss, Inc. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. TOTTORI UNIV,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI,JAPAN. NR 21 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1995 VL 13 IS 1 BP 18 EP 24 DI 10.1002/gcc.2870130104 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QW163 UT WOS:A1995QW16300003 PM 7541639 ER PT J AU ZENKLUSEN, JC OSHIMURA, M BARRETT, JC CONTI, CJ AF ZENKLUSEN, JC OSHIMURA, M BARRETT, JC CONTI, CJ TI HUMAN-CHROMOSOME-II INHIBITS TUMORIGENICITY OF A MURINE SQUAMOUS-CELL CARCINOMA CELL-LINE SO GENES CHROMOSOMES & CANCER LA English DT Article ID SUPPRESSES TUMORIGENICITY; WILMS-TUMORS; HETEROZYGOSITY; GENE; EXPRESSION AB Loss of heterozygosity (LOH) of mouse chromosome 7 has been consistently demonstrated in chemically induced murine squamous cell carcinomas (SCCs). The region of this chromosome presenting LOH in the mouse tumors is syntenic to human chromosome segments IIp15 and IIq. To determine whether the introduction of human chromosome (Hchr) II can suppress the growth of murine SCC, we injected four clones of a chemically induced murine SCC cell line bearing an Hchr II into athymic BALB/c nude mice. All microcell hybrid clones with Hchr II (CH72/Hchr II) had latency periods twice as long as those of the parental CH72 cells and control hybrids containing a Hchr 12. Tumor-derived cells from CH72/Hchr II hybrids had lost centromeric and telomeric sequences from Hchr II. All repressed cell lines grew significantly more slowly in vitro than did the controls. These results suggest that Hchr II contains a tumor-suppressor gene capable of inhibiting tumorigenicity in chemically induced SCC, confirming common pathways in the development of human neoplasias and the murine model. (C) 1995 Wiley-Liss, Inc. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DIV RES,SMITHVILLE,TX 78957. TOTTORI UNIV,SCH LIFE SCI,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI,JAPAN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA53123] NR 22 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1995 VL 13 IS 1 BP 47 EP 53 DI 10.1002/gcc.2870130108 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QW163 UT WOS:A1995QW16300007 PM 7541643 ER PT J AU WU, TC LICHTEN, M AF WU, TC LICHTEN, M TI FACTORS THAT AFFECT THE LOCATION AND FREQUENCY OF MEIOSIS-INDUCED DOUBLE-STRAND BREAKS IN SACCHAROMYCES-CEREVISIAE SO GENETICS LA English DT Article ID MEIOTIC GENE CONVERSION; YEAST CHROMOSOME-III; INITIATION SITE; RECOMBINATION; DNA; TRANSCRIPTION; EXPRESSION; METABOLISM; SYNAPSIS; TELOMERE AB Double-strand DNA breaks (DSBs) initiate meiotic recombination in Saccharomyces cerevisiae. DSBs occur at sites that are hypersensitive in nuclease digests of chromatin, suggesting a role for chromatin structure in determining DSB location. We show here that the frequency of DSBs at a site is not determined simply by DNA sequence or by features of chromatin structure. An arg4-containing plasmid was inserted at several different locations in the yeast genome. Meiosis-induced DSBs occurred at similar sites in pBR322-derived portions of the construct at all insert loci, and the frequency of these breaks varied in a manner that mirrored the frequency of meiotic recombination in the arg4 portion of the insert. However, DSBs did not occur in the insert-borne arg4 gene at a site that is frequently broken at the normal ARG4 locus, even though the insert-borne arg4 gene and the normal ARG4 locus displayed similar DNase I hypersensitivity patterns. Deletions that removed active DSB sites from an insert at HIS4 restored breaks to the insert-borne arg4 gene and to a DSB site in flanking chromosomal sequences. We conclude that the frequency of DSB at a site can be affected by sequences several thousand nucleotides away and suggest that this is because of competition between DSB sites for locally limited factors. C1 NCI,DIV CANC BIOL DIAG & CTR,BIOCHEM LAB,BETHESDA,MD 20892. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 40 TC 138 Z9 142 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1995 VL 140 IS 1 BP 55 EP 66 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA QV521 UT WOS:A1995QV52100006 PM 7635308 ER PT J AU OHTAKE, Y WICKNER, RB AF OHTAKE, Y WICKNER, RB TI KRB1, A SUPPRESSOR OF MAK7-1 (A MUTANT RPL4A), IS RPL4B, A 2ND RIBOSOMAL-PROTEIN L4 GENE, ON A FRAGMENT OF SACCHAROMYCES CHROMOSOME-XII SO GENETICS LA English DT Article ID DOUBLE-STRANDED-RNA; CEREVISIAE; YEAST; REPLICATION; PLASMID AB The mak7-1 mutant loses the killer toxin-encoding M(1) dsRNA. MAK7 is RPL4A, one of two genes encoding ribosomal protein L4. KRB1 is a dominant suppressor of mak7-1 that is tightly centromere-linked, but not linked to centromere markers of chromosomes I-XVI. Our orthogonal field agarose gel electrophoresis analysis of chromosomal DNA from strains with KRB1 shows a novel band of similar to 250 kb. This band hybridizes with an RPL4B-specific probe, but not an RPL4A (MAK7)-specific probe. The RPL4B-specific probe also hybridizes to chromosome XII where the original RPL4B is located. KRB1 is meiotically linked to this extra chromosome. Disruption of either the RPL4B gene on chromosome XII or that on the extra chromosome results in loss of the killer phenotype and a decreased concentration of free 60S subunits. Thus, the RPL4B on the extra chromosome is KRB1 and is active. The extra chromosome contains chromosome XII sequence between Lambda 5345 clone (ATCC70558) and Lambda 6639 clone (ATCC71085) of Olson's Lambda library, indicating that KRB1 represents a chromosomal rearrangement involving chromosome XII and explaining the earlier genetic data. C1 NIDDKD, BIOCHEM PHARMACOL LAB, GENET SIMPLE EUKARYOTES SECT, BETHESDA, MD 20892 USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD MAY PY 1995 VL 140 IS 1 BP 129 EP 137 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA QV521 UT WOS:A1995QV52100012 PM 7635280 ER PT J AU HUSTAD, CM PERRY, WL SIRACUSA, LD RASBERRY, C COBB, L CATTANACH, BM KOVATCH, R COPELAND, NG JENKINS, NA AF HUSTAD, CM PERRY, WL SIRACUSA, LD RASBERRY, C COBB, L CATTANACH, BM KOVATCH, R COPELAND, NG JENKINS, NA TI MOLECULAR-GENETIC CHARACTERIZATION OF 6 RECESSIVE VIABLE ALLELES OF THE MOUSE AGOUTI LOCUS SO GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; MOTH-EATEN; PATHOLOGY; MUTATIONS; YELLOW; MICE; MOTHEATEN; SECRETION; LETHALITY; PCR AB The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (a(mJ) a(u), a(da), a(16H), a(18H), a(e)) were examined at both the RNA and DNA level. Two of the alleles, a(16H) and a(e), result from mutations in the agouti coding region. Four alleles (a(mJ) a(u), a(18H), and a(da)) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a(18H), also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten, (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a(18H) DNA are consistent with the hypothesis that a(18H) results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder. C1 MRC,DIV GENET,RADIOBIOL UNIT,DIDCOT OX11 0RD,OXON,ENGLAND. PATHOL ASSOCIATES INC,FREDERICK,MD 21701. RP HUSTAD, CM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-46000] NR 45 TC 81 Z9 83 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1995 VL 140 IS 1 BP 255 EP 265 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA QV521 UT WOS:A1995QV52100021 PM 7635290 ER PT J AU FERRY, WL HUSTAD, CM SWING, DA JENKINS, NA COPELAND, NG AF FERRY, WL HUSTAD, CM SWING, DA JENKINS, NA COPELAND, NG TI A TRANSGENIC MOUSE ASSAY FOR AGOUTI PROTEIN-ACTIVITY SO GENETICS LA English DT Article ID FUSION GENE; MICE; YELLOW; LOCUS; DNA; AMPLIFICATION; EXPRESSION; SEQUENCES; SECRETION; LETHALITY AB The mouse agouti gene encodes an 131 amino acid paracrine signaling molecule that instructs hair follicle melanocytes to switch from making black to yellow pigment. Expression of agouti during the middle part of the hair growth cycle in wild-type mice produces a yellow band on an otherwise black hair. The ubiquitous unregulated expression of agouti in mice carrying dominant yellow alleles is associated with pleiotropic effects including increased yellow pigment in the coat, obesity, diabetes and increased tumor susceptibility. Agouti shows no significant homology to known genes, and the molecular analysis of agouti alleles has shed little new light on the important functional elements of the agouti protein. In this paper, we show that agouti expression driven by the human beta-ACTIN promoter produces obese yellow transgenic mice and that this can be used as an assay for agouti activity. We used this assay to evaluate a point mutation associated with the a(16H) allele within the region encoding agouti's putative signal sequence and our results suggest that this mutation is sufficient to cause the a(16H) phenotype. Thus, in vitro mutagenesis followed by the generation of transgenic mice should allow us to identify important functional elements of the agouti protein. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 45 TC 7 Z9 7 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1995 VL 140 IS 1 BP 267 EP 274 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QV521 UT WOS:A1995QV52100022 ER PT J AU ZHADANOV, AB COPELAND, NG GIBERT, DJ JENKINS, NA WESTPHAL, H AF ZHADANOV, AB COPELAND, NG GIBERT, DJ JENKINS, NA WESTPHAL, H TI GENOMIC STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE MOUSE LIM/HOMEOBOX GENE LHX3 SO GENOMICS LA English DT Article ID MESSENGER-RNA DEGRADATION; DROSOPHILA NOTCH; HOMEOBOX GENE; DOMAIN; EXPRESSION; PROTEINS; SEQUENCE; BINDING; HOMOLOG; ELEGANS AB We have previously cloned the murine Lhx3 cDNA that encodes a predicted protein containing two tandemly repeated LIM domains and a homeodomain. Early expression of Lhx3 in oral ectoderm that is committed to contribute to the anterior and intermediate lobes of the pituitary and its perseverance in the adult gland strongly suggest an involvement of the gene in mediating and maintaining the differentiation program of this important endocrine system. Additional functions are suggested by the fact that Lhx3 is also expressed bilaterally along the spinal cord and the hindbrain at early stages of mouse development. Here we report the structural organization and chromosomal localization of the Lhx3 gene. The gene is composed of six exons and five introns. Two different exons, Ia and Ib, appear to be alternatively spliced to exon II. The first LIM domain is encoded by exon II and the second by exon III. The homeobox is shared by exons IV and V. We have mapped Lhx3 to the proximal region of mouse chromosome 2 in a region that shares homology with human chromosomes 9q and 10p. (C) 1995 Academic Press, Inc. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 43 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1995 VL 27 IS 1 BP 27 EP 32 DI 10.1006/geno.1995.1004 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RA144 UT WOS:A1995RA14400005 PM 7665181 ER PT J AU LITT, M KRAMER, P KORT, E FAIN, P COX, S ROOT, D WHITE, R WEISSENBACH, J DONISKELLER, H GATTI, R WEBER, J NAKAMURA, Y JULIER, C HAYASHI, K SPURR, N DEAN, M MANDEL, J KIDD, K KRUSE, T RETIEF, A BALE, A MEO, T VERGNAUD, G WARREN, S WILLARD, HF AF LITT, M KRAMER, P KORT, E FAIN, P COX, S ROOT, D WHITE, R WEISSENBACH, J DONISKELLER, H GATTI, R WEBER, J NAKAMURA, Y JULIER, C HAYASHI, K SPURR, N DEAN, M MANDEL, J KIDD, K KRUSE, T RETIEF, A BALE, A MEO, T VERGNAUD, G WARREN, S WILLARD, HF TI THE CEPH CONSORTIUM LINKAGE MAP OF HUMAN-CHROMOSOME-11 SO GENOMICS LA English DT Article ID SYNDROME TYPE-I; HUMAN GENOME; GENETIC-LINKAGE; LONG ARM AB The CEPH consortium framework map of chromosome 11 is presented. The map was generated from CEPH family DNAs with 181 probe/enzyme combinations contributed by 20 laboratories. Seventy-seven of the loci are defined by microsatellite polymorphisms that can be typed by the PCR. A total of 42 loci have been placed on the map with likelihood support of at least 1000:1. The female, male, and sex-average maps extend for 179.6, 110.8, and 145.3 cM, respectively. The largest interval on the sex-average map is less than 11 cM, and the average distance between uniquely placed loci is 4 cM. The genotypic data obtained for map construction have been used to identify the positions of crossovers on the chromosomes of CEPH family children, allowing the localization of new markers without computationally intensive likelihood models and providing a basis for efficient extension of the linkage map to higher resolution. (C) 1995 Academic Press, Inc. C1 OREGON HLTH SCI UNIV,DEPT MOLEC & MED GENET,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. UNIV UTAH,DEPT GENET EPIDEMIOL,SALT LAKE CITY,UT. IMPERIAL CANC RES FUND,CLARE HALL LABS,POTTERS BAR EN6 3LD,HERTS,ENGLAND. UNIV UTAH,MED CTR,HOWARD HUGHES MED INST,SALT LAKE CITY,UT. INST PASTEUR,UNITE RECOMBINAISON & EXPRESS GENET,PARIS,FRANCE. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90024. MARSHFIELD MED RES FDN,MARSHFIELD,WI 54449. INST CANC RES,DIV BIOCHEM,TOKYO,JAPAN. CEPH,PARIS,FRANCE. NATL CANC CTR,RES INST,DIV ONCOGENE,TOKYO 104,JAPAN. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD. INST CHIM BIOL,STRASBOURG,FRANCE. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. AARHUS UNIV,INST HUMAN GENET,DK-8000 AARHUS,DENMARK. UNIV STELLENBOSCH,DEPT CYTOGENET,TYGERBERG 7505,SOUTH AFRICA. INST PASTEUR,PARIS,FRANCE. CTR ETUD BOUCHET,F-91710 VERT LE PETIT,FRANCE. EMORY UNIV,SCH MED,DEPT BIOCHEM,ATLANTA,GA 30322. CASE WESTERN RESERVE UNIV,SCH MED,DEPT GENET,CLEVELAND,OH 44106. RP LITT, M (reprint author), OREGON HLTH SCI UNIV,DEPT BIOCHEM,L333,PORTLAND,OR 97201, USA. RI Vergnaud, Gilles/P-1304-2015 OI Vergnaud, Gilles/0000-0003-0913-194X FU NHGRI NIH HHS [HG-00022, HG-00360] NR 36 TC 26 Z9 26 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1995 VL 27 IS 1 BP 101 EP 112 DI 10.1006/geno.1995.1011 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RA144 UT WOS:A1995RA14400012 PM 7665156 ER PT J AU KERSHAW, EE CHUA, SC WILLIAMS, JA MURPHY, EM LEIBEL, RL AF KERSHAW, EE CHUA, SC WILLIAMS, JA MURPHY, EM LEIBEL, RL TI MOLECULAR MAPPING OF SSRS FOR PGM1 AND C8B IN THE VICINITY OF THE RAT FATTY LOCUS SO GENOMICS LA English DT Article ID HUMAN CHROMOSOME-1; COMPLEMENTARY-DNA; ALPHA-SUBUNIT; BETA-SUBUNIT; ZUCKER RATS; OBESITY; IDENTIFICATION; SEQUENCE; HOMOLOGY; MAPS AB Recessive mutations at the rat fatty locus (fa, fa(cp)), which produce obesity, insulin resistance, and diabetes, provide useful experimental models for similar phenotypes in humans, The molecular pathogenesis of the metabolic phenotype in animals segregating for fa is unknown and difficult to study once the confounding metabolic effects of obesity are present. Although various experimental methods distinguish preobese from lean rats (phenotypic markers and molecular markers genetically linked 60 fatty), technical difficulties limit their utility, We report the identification of two (GT)(n) simple sequence repeats (SSRs) near the rat phosphoglucomutase gene (Pgm1) gene and two SSRs, (GA)(n) and (GT)(n), near the rat complement component 8 beta gene (C8b). These SSRs map to an similar to 4-cM interval flanking the fatty locus on rat chromosome 5, Use of these molecular markers in combination offers an improved method for early assessment of gene dosage for fa and hence for studying the fundamental molecular physiology underlying the derangements of metabolism and behavior resulting from mutations in this gene. (C) 1995 Academic Press, Inc. C1 ROCKEFELLER UNIV,HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. HOWARD HUGHES MED INST,CHEVY CHASE,MD 20815. VASSAR COLL,NATL INST HLTH,ANIM MODE CORE LAB,DEPT BIOL,POUGHKEEPSIE,NY 12601. RI Kershaw, Erin/G-9587-2013 FU NICHD NIH HHS [HD28047]; NIDDK NIH HHS [DK47473] NR 33 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1995 VL 27 IS 1 BP 149 EP 154 DI 10.1006/geno.1995.1017 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RA144 UT WOS:A1995RA14400018 PM 7665162 ER PT J AU TAKAI, S LONG, JE YAMADA, K MIKI, T AF TAKAI, S LONG, JE YAMADA, K MIKI, T TI CHROMOSOMAL LOCALIZATION OF THE HUMAN ECT2 PROTOONCOGENE TO 3Q26.1-]Q26.2 BY SOMATIC-CELL ANALYSIS AND FLUORESCENCE IN-SITU HYBRIDIZATION SO GENOMICS LA English DT Note ID MOUSE MYELOBLASTIC LEUKEMIAS; INSITU HYBRIDIZATION; INTEGRATION REGIONS; GENE; VIRUS C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP TAKAI, S (reprint author), INT MED CTR JAPAN,RES INST,DEPT GENET,SHINJUKU KU,1-21-1 TOYAMA CHO,TOKYO 162,JAPAN. NR 13 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1995 VL 27 IS 1 BP 220 EP 222 DI 10.1006/geno.1995.1033 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RA144 UT WOS:A1995RA14400034 PM 7665179 ER PT J AU BUTLER, RN COLLINS, KS MEIER, DE MULLER, CF PINN, VW AF BUTLER, RN COLLINS, KS MEIER, DE MULLER, CF PINN, VW TI OLDER WOMENS HEALTH - TAKING THE PULSE REVEALS GENDER-GAP IN MEDICAL-CARE - A ROUND-TABLE DISCUSSION .1. SO GERIATRICS LA English DT Article ID CANCER AB In the United States, for every 100 men age 65 and older, there are 147 women, a ratio that has social and medical consequences. Five panelists ''take the pulse'' of older women's health in general and in the offices of primary care physicians in particular. They assess the status of medical education and the need to include older women in research and drug trials, issues of gender bias in health insurance and quality of treatment, ways to improve the use of preventive health services-such as mammography and Pap smears-by older women, and the role of office physicians in identifying and helping victims of domestic violence. C1 INT LONGEV CTR,NEW YORK,NY. COMMONWEALTH FUND,NEW YORK,NY. NIH,OFF WOMENS HLTH,BETHESDA,MD 20892. RP BUTLER, RN (reprint author), MT SINAI MED CTR,HENRY L SCHWARTZ DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 21 TC 2 Z9 2 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 MAY PY 1995 VL 50 IS 5 BP 39 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA QY187 UT WOS:A1995QY18700004 PM 7737526 ER PT J AU RAO, VSR BALAJI, PV QASBA, PK AF RAO, VSR BALAJI, PV QASBA, PK TI CONTROVERSIAL IDURONATE RING CONFORMATION IN DERMATAN SULFATE SO GLYCOBIOLOGY LA English DT Letter ID MOLECULAR MECHANICS; COUPLING-CONSTANTS; NMR-SPECTROSCOPY; KARPLUS EQUATION; H-1-NMR; SULFATE; GLYCOPROTEINS; RESOLUTION; PROTON; STATE C1 NCI, MATH BIOL LAB, BETHESDA, MD 20892 USA. NR 26 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD MAY PY 1995 VL 5 IS 3 BP 273 EP 276 DI 10.1093/glycob/5.3.273 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RA047 UT WOS:A1995RA04700001 PM 7655164 ER PT J AU CRYSTAL, RG JAFFE, A BRODY, S MASTRANGELI, A MCELVANEY, NG ROSENFELD, M CHU, CS DANEL, C HAY, J EISSA, T AF CRYSTAL, RG JAFFE, A BRODY, S MASTRANGELI, A MCELVANEY, NG ROSENFELD, M CHU, CS DANEL, C HAY, J EISSA, T TI A PHASE-1 STUDY, IN CYSTIC-FIBROSIS PATIENTS, OF THE SAFETY, TOXICITY, AND BIOLOGICAL EFFICACY OF A SINGLE ADMINISTRATION OF A REPLICATION DEFICIENT, RECOMBINANT ADENOVIRUS CARRYING THE CDNA OF THE NORMAL CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE IN THE LUNG SO HUMAN GENE THERAPY LA English DT Article C1 CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. NHLBI,BETHESDA,MD 20892. RP CRYSTAL, RG (reprint author), ROCKEFELLER UNIV HOSP,1230 YORK AVE,NEW YORK,NY 10021, USA. RI McElvaney, Noel/A-6809-2010 NR 0 TC 39 Z9 39 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 1995 VL 6 IS 5 BP 643 EP 666 DI 10.1089/hum.1995.6.5-643 PG 24 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA QZ425 UT WOS:A1995QZ42500011 PM 7578401 ER PT J AU BRAUCH, H KISHIDA, T GLAVAC, D CHEN, F PAUSCH, F HOFLER, H LATIF, F LERMAN, MI ZBAR, B NEUMANN, HPH AF BRAUCH, H KISHIDA, T GLAVAC, D CHEN, F PAUSCH, F HOFLER, H LATIF, F LERMAN, MI ZBAR, B NEUMANN, HPH TI VON HIPPEL-LINDAU (VHL) DISEASE WITH PHEOCHROMOCYTOMA IN THE BLACK-FOREST REGION OF GERMANY - EVIDENCE FOR A FOUNDER EFFECT SO HUMAN GENETICS LA English DT Article ID DIAGNOSIS; FEATURES; LOCUS; GENE AB We identified a germline missense mutation at nucleotide 505 (T to C) of the VHL tumor suppressor gene in 14, apparently unrelated, VHL type 2A families from the Black Forest region of Germany. This mutation was previously identified in two VHL 2A families living in Pennsylvania (USA). All affected individuals in the 16 families shared the same VHL haplotype indicating a founder effect. This missense mutation at codon 169 (Tyr to His) would probably cause an alteration in the structure of the putative VI-IL protein. The association of this distinct mutation with the pheochromocytoma phenotype in VHL may help to elucidate the genetic mechanism of carcinogenesis in this multi tumor cancer syndrome. C1 NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21702. NATL INST CHEM,LJUBLJANA,SLOVENIA. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. UNIV FREIBURG,DEPT MED,DIV NEPHROL & HYPERTENS,D-79106 FREIBURG,GERMANY. RP BRAUCH, H (reprint author), TECH UNIV MUNICH,INST PATHOL,MOLEC PATHOL LAB,TROGERSTR 32,D-81675 MUNICH,GERMANY. NR 24 TC 118 Z9 119 U1 1 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1995 VL 95 IS 5 BP 551 EP 556 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QX500 UT WOS:A1995QX50000013 PM 7759077 ER PT J AU BENTLEY, D GREEN, E WATERSTON, R AF BENTLEY, D GREEN, E WATERSTON, R TI CSHL MAPPING AND SEQUENCING MEETING HELD SO HUMAN GENOME NEWS LA English DT Editorial Material C1 SANGER CTR,CAMBRIDGE,ENGLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. WASHINGTON UNIV,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUM GENOME MANAGE INF SYSTEM PI OAK RIDGE PA OAK RIDGE NATIONAL LABORATORY PO BOX 2008, OAK RIDGE, TN 37831-6050 SN 1050-6101 J9 HUM GENOME NEWS JI Hum. Genome News PD MAY-JUN PY 1995 VL 7 IS 1 BP 5 EP 7 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RN921 UT WOS:A1995RN92100002 ER PT J AU WILLIAMS, AO WARD, JM LI, JF JACKSON, MA FLANDERS, KC AF WILLIAMS, AO WARD, JM LI, JF JACKSON, MA FLANDERS, KC TI IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING GROWTH FACTOR-BETA(1) IN KAPOSIS-SARCOMA SO HUMAN PATHOLOGY LA English DT Article DE KAPOSIS SARCOMA; TRANSFORMING GROWTH FACTOR BETA-1; HUMAN IMMUNODEFICIENCY VIRUS-1; ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNOHISTOCHEMISTRY ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM CULTURE; SMOOTH-MUSCLE CELLS; FACTOR-BETA; ENDEMIC AFRICAN; HIV-INFECTION; AIDS; INVITRO; LESIONS; PATHOGENESIS AB Immunohistochemical localization of transforming growth factor beta 1 (TGF-beta 1) was studied in Kaposi's sarcoma (KS) tissues obtained from autopsy and biopsy materials of patients with and without acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection. There was no difference in the localization and distribution of TGF-beta 1 in KS tissues regardless of the HIV-1 status of the patients. Rabbit polyclonal antibodies to synthetic peptides, corresponding to the first 30 amino acids of mature TGF-beta 1 anti-LC(1-30), and anti-CC(1-30), were used for localization of intracellular and extracellular TGF-beta 1. An antibody to a peptide corresponding to amino acids 266 to 278 of the TGF-beta 1. precursor sequence anti-Pre(266 to 278) was used to detect the TGF-beta 1 precursor and the latency-associated peptide. Intracellular mature TGF-beta 1 was demonstrated in mononuclear cells, presumably macrophages, within KS tumors but not in spindle-shaped KS cells. Extracellular mature TGF-beta 1 was localized in the basement membranes of blood vessels and fibrous capsules of KS tumors. Intracellular reactivity to anti-Pre was localized in vascular smooth muscle cells and pericytes within the tumor, in variable proportions of spindle-shaped KS cells, and also in macrophage-like cells. These cells appear to be the production sites of TGF-beta 1, which may exert paracrine as well as autocrine proliferative effects. Copyright (C) 1995 by W.B. Saundes Company C1 NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,BETHESDA,MD 20892. N CENT BRONX HOSP,DEPT PATHOL,NEW YORK,NY. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. RP WILLIAMS, AO (reprint author), NCI,DIV CANC ETIOL,CHEMOPREVENT LAB,EXPTL PATHOL LAB,BLDG 41,ROOM C-105,BETHESDA,MD 20892, USA. NR 60 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1995 VL 26 IS 5 BP 469 EP 473 DI 10.1016/0046-8177(95)90241-4 PG 5 WC Pathology SC Pathology GA QY805 UT WOS:A1995QY80500002 PM 7750930 ER PT J AU POTASHNIK, G LUNENFELD, E SHWARTZ, I GLEZERMAN, M ROBERTS, CT LEROITH, D SHARONI, Y LEVY, J AF POTASHNIK, G LUNENFELD, E SHWARTZ, I GLEZERMAN, M ROBERTS, CT LEROITH, D SHARONI, Y LEVY, J TI ENDOGENOUS PLASMA GROWTH-HORMONE AND THE OCCURRENCE OF PREGNANCIES IN PATIENTS UNDERGOING IN-VITRO FERTILIZATION AND EMBRYO-TRANSFER WITH OVARIAN STIMULATION SO HUMAN REPRODUCTION LA English DT Article DE GROWTH HORMONE; IGF-I; IGFBP-3; IVF AND EMBRYO TRANSFER; PREGNANCIES; UTERINE RECEPTIVITY ID HUMAN MENOPAUSAL GONADOTROPIN; OVULATION INDUCTION; COTREATMENT; TRIAL; WOMEN AB This study was undertaken to investigate a possible relationship between endogenous secretion of growth hormone (GH) during ovarian stimulation and treatment outcome in patients undergoing in-vitro fertilization (IVF) and embryo transfer, Plasma samples obtained from 19 women who had successfully completed all stages of IVF/embryo transfer were analysed retrospectively. Based on the increase in GH during treatment, 11 GH responders and eight GH non-responders were identified, Mean daily GH concentrations for the GH responders and GH nonresponders were 3.5 +/- 1.8 and 1.8 +/- 0.8, 5.4 +/- 2.3 and 0.5 +/- 0.2, and 9.0 +/- 1.9 and 0.7 +/- 0.1 ng/ml (P < 0.05) for days 10, 11 and 12 respectively, Plasma insulin-like growth factor-I slightly increased with treatment in both groups. No significant difference between these groups was found in relation to treatment duration, number of human menopausal gonadotrophin ampoules used, oestradiol peak values, and number of oocytes retrieved or fertilization rate, Seven of the 11 GH responder women conceived in comparison with one pregnancy among eight GH nonresponder patients (P < 0.05), In view of the absence of differences in the clinical and laboratory parameters, we suggest that the occurrence of pregnancies among GH responder patients might be related to a positive local effect of GH or its mediators on uterine receptivity at the time of nidation. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR KUPAT HOLIM,CLIN BIOCHEM UNIT,IL-84105 BEER SHEVA,ISRAEL. NIDDK,DIABET BRANCH,BETHESDA,MD 20892. RP POTASHNIK, G (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR KUPAT HOLIM,DEPT OBSTET & GYNECOL,IL-84105 BEER SHEVA,ISRAEL. RI Lunenfeld, EITAN/F-1662-2012 NR 15 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 1995 VL 10 IS 5 BP 1065 EP 1069 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RC659 UT WOS:A1995RC65900011 PM 7657742 ER PT J AU SCHULKIN, J KLEINDORFER, P AF SCHULKIN, J KLEINDORFER, P TI EQUITY DECISIONS - ECONOMIC-DEVELOPMENT AND ENVIRONMENTAL PRUDENCE SO HUMAN RIGHTS QUARTERLY LA English DT Article C1 UNIV PENN,WHARTON RISK MANAGEMENT & DECIS PROC CTR,PHILADELPHIA,PA 19104. RP SCHULKIN, J (reprint author), NIMH,BEHAV NEUROSCI UNIT,BETHESDA,MD 20892, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION 2715 NORTH CHARLES ST, BALTIMORE, MD 21218 SN 0275-0392 J9 HUM RIGHTS QUART JI Hum. Rights Q. PD MAY PY 1995 VL 17 IS 2 BP 382 EP 397 PG 16 WC Political Science; Social Issues SC Government & Law; Social Issues GA QV055 UT WOS:A1995QV05500007 ER PT J AU WAGTMANN, N BIASSONI, R CANTONI, C VERDIANI, S MALNATI, MS VITALE, M BOTTINO, C MORETTA, L MORETTA, A LONG, EO AF WAGTMANN, N BIASSONI, R CANTONI, C VERDIANI, S MALNATI, MS VITALE, M BOTTINO, C MORETTA, L MORETTA, A LONG, EO TI MOLECULAR CLONES OF THE P58 NK CELL-RECEPTOR REVEAL IMMUNOGLOBULIN-RELATED MOLECULES WITH DIVERSITY IN BOTH THE EXTRACELLULAR AND INTRACELLULAR DOMAINS SO IMMUNITY LA English DT Article ID NATURAL-KILLER-CELLS; ANTIGEN RECOGNITION; I ALLELES; EXPRESSION; HLA; SPECIFICITY; LYSIS; SUPERFAMILY; PROTECTION; ACTIVATION AB Recognition of major histocompatibility class I molecules on target cells by natural killer (NK) cells confers selective protection from NK-mediated lysis. Crosslinking of the p58 NK receptor, involved in the recognition of HLA-C alleles, delivers a negative signal that prevents target cell lysis. Molecular cloning of the p58 NK receptor reported here revealed a new member of the immunoglobulin superfamily. Five distinct p58 receptors, with sequence diversity in the immunoglobulin-related domains, were identified in a single individual. All NK clones tested expressed at least one p58 member. Three different types of transmembrane and cytoplasmic domains exist, even among receptors with closely related extracellular domains. These data revealed a repertoire of NK cells with clonally distributed p58 receptors exhibiting diversity in both extracellular and intracellular domains. C1 IST NAZL RIC CANC,I-16132 GENOA,ITALY. UNIV GENOA,IST ISTOL & EMBRIOL GEN,I-16132 GENOA,ITALY. RP WAGTMANN, N (reprint author), NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011; Vitale, Massimo/G-5135-2016 OI Long, Eric/0000-0002-7793-3728; Vitale, Massimo/0000-0001-5372-7885 NR 43 TC 528 Z9 534 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1995 VL 2 IS 5 BP 439 EP 449 DI 10.1016/1074-7613(95)90025-X PG 11 WC Immunology SC Immunology GA QZ430 UT WOS:A1995QZ43000002 PM 7749980 ER PT J AU STUBER, E NEURATH, M CALDERHEAD, D FELL, HF STROBER, W AF STUBER, E NEURATH, M CALDERHEAD, D FELL, HF STROBER, W TI CROSS-LINKING OF OX40 LIGAND, A MEMBER OF THE TNF/NGF CYTOKINE FAMILY, INDUCES PROLIFERATION AND DIFFERENTIATION IN MURINE SPLENIC B-CELLS SO IMMUNITY LA English DT Article ID TUMOR NECROSIS FACTOR; HELPER T-CELLS; DEPENDENT ACTIVATION; SENSITIVE METHOD; LYMPHOCYTES-B; ANTIGEN; CD40; PROTEIN; EXPRESSION; MEMBRANES AB OX40 is a member of the TNF/NGF-receptor family expressed on activated T cells, whose ligand is found on activated T and a cells. in the present study, we show that cross-linking of OX40L on CD40L-stimulated B cells, alpha lgD dextran-stimulated B cells, or both results in a significantly enhanced proliferative response with no change in the cell survival rate. Furthermore, OX40 stimulation increases immunoglobulin heavy chain mRNA levels and immunoglobulin secretion, which could not be blocked by anti-cytokine antibodies. In additional molecular studies, we show that OX40L cross-linking results in the down-regulation of the transcription factor BSAP. This, in turn, leads to a change in the in vivo binding pattern of the immuno-globulin heavy chain gene 3' alpha enhancer, suggesting its activation. This effect may thus be one mechanism for OX40-induced increase in immunoglobulin secretion. in conclusion, our data suggest that the OX40-OX40L interaction is a novel pathway in T cell-dependent B cell proliferation and differentiation. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC IMMUNOL,SEATTLE,WA 98121. RP STUBER, E (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 49 TC 306 Z9 316 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1995 VL 2 IS 5 BP 507 EP 521 DI 10.1016/1074-7613(95)90031-4 PG 15 WC Immunology SC Immunology GA QZ430 UT WOS:A1995QZ43000008 PM 7749983 ER PT J AU LANE, HC DAVEY, RT AF LANE, HC DAVEY, RT TI DIAGNOSIS OF HIV-INFECTION SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; BRANCHED DNA BDNA; P24 ANTIGEN; REVERSE-TRANSCRIPTION; PLASMA VIREMIA; MESSENGER-RNA; TYPE-1; QUANTITATION AB In recent years there has been considerable refinement in our ability to diagnose infection with HIV even early in the course of disease. Despite the advances in virologic assays, however, the mainstay of diagnosis remains the screening HIV ELISA and the confirmatory Western blot assay. For situations where the reliability of serologic methods is uncertain, such as very early after exposure or in the case of potential vertical transmission to the neonate, more sophisticated laboratory methods that measure the direct presence of viral genetic material have been developed. Direct DNA or RNA amplification methods and nucleic acid hybridization methodologies are highly sensitive and specific assays whose utility beyond the research setting must be assessed against a background of increased cost and technical requirements. RP LANE, HC (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1995 VL 15 IS 2 BP 367 EP 386 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA QY656 UT WOS:A1995QY65600013 ER PT J AU CHEN, T SWANSON, J WILSON, J BELLAND, RJ AF CHEN, T SWANSON, J WILSON, J BELLAND, RJ TI HEPARIN PROTECTS OPA(+) NEISSERIA-GONORRHOEAE FROM THE BACTERICIDAL ACTION OF NORMAL HUMAN SERUM SO INFECTION AND IMMUNITY LA English DT Article ID 5'-MONOPHOSPHO-N-ACETYL NEURAMINIC ACID; OUTER-MEMBRANE PROTEIN; GONOCOCCUS INFECTION; LIPOPOLYSACCHARIDE ALTERATION; IMMUNOGLOBULIN-G; PHASE VARIATION; SIALIC-ACID; RESISTANCE; OPACITY; LIPOOLIGOSACCHARIDE AB The pathobiological significance of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) changes in gonorrheal disease are poorly understood. We assessed variants of strain MS11mk with different LOS and Opa phenotypes for their liability to killing by normal human sera. LOS differences correlated with strikingly disparate susceptibilities to serum killing; LOSa variants were serum resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants enhanced their survival (as reported previously). Opa phenotype had little influence on the killing of serum-sensitive LOSb cells that were incubated directly in normal human sera, but preincubation of Opa(+) LOSb variants in heparin increased their serum resistance whereas Opa(-) LOSb variants showed no change. Some Opa proteins conferred slightly higher resistance than others, but heparin preincubation increased serum resistance for variants expressing each of seven Opa proteins. These in vitro phenomena may relate to conditions within the male urethra where sulfate-containing proteoglycans are abundant and where antibody and complement may transude from blood plasma. The results suggest that the selective advantage for Opa(+) Neisseria gonorrhoeae bacteria observed in vivo may reflect their ability to utilize host cell components to resist kilting by host defenses. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. NR 53 TC 28 Z9 28 U1 0 U2 1 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 MAY PY 1995 VL 63 IS 5 BP 1790 EP 1795 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QU941 UT WOS:A1995QU94100026 PM 7729887 ER PT J AU MALIK, A HOUGHTEN, R CORRADIN, G BUUS, S BERZOFSKY, JA HOFFMAN, SL AF MALIK, A HOUGHTEN, R CORRADIN, G BUUS, S BERZOFSKY, JA HOFFMAN, SL TI IDENTIFICATION OF A NONAMERIC H-2K(K)-RESTRICTED CD8+ CYTOTOXIC T-LYMPHOCYTE EPITOPE ON THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN SO INFECTION AND IMMUNITY LA English DT Article ID CLASS-I; PROTECTIVE IMMUNITY; PEPTIDES; CELLS; MALARIA; ANTIGEN; MICE; IMMUNIZATION; ASSOCIATION; MOLECULES AB Class I-restricted CD8(+) cytotoxic T lymphocytes (CTL) against the circumsporozoite protein (CSP) protect mice against the rodent malaria parasite, Plasmodium yoelii, and vaccines designed to produce protective CTL against the P. falciparum CSP (PfCSP) are under development. Humans and B10.BR (H-2(k)) mice have been shown to have CD8(+) CTL activity against a 23-amino-acid region of the PfCSP (residues 368 to 390 from the PfCSP 7G8 sequence) that is too long to bind directly to class I major histocompatibility complex molecules. To identify within this 23-amino-acid peptide a shorter peptide that binds to an H-2(k) class I major histocompatibility molecule, a primarily CD8(+) (97.8%) T-cell line (PfCSP TCL.1) was produced by immunizing B10.BR mice with recombinant vaccinia virus expressing the PfCSP and stimulating in vitro spleen cells from these immunized mice with L cells transfected with the PfCSP gene (LPF cells), PfCSP TCL.1 lysed LPF cells and L cells pulsed with peptide PfCSP 7G8 368-390. When 15 overlapping nonamer peptides spanning the 368 to 390 sequence were tested, only one peptide, PfCSP 7G8 375-383 (Y E N D I E K K I), which includes an H-2K(k)-binding motif E at amino acid residue 2, and I at residue 9, sensitized targets for lysis by PfCSP TCL.1. Furthermore, a 10(3)- to 10(4)-fold lower concentration of the nonamer than that of the 23-amino-acid peptide was required to sensitize target cells for lysis by PfCSP TCL.1. Presentation by H-2K(k) was demonstrated by using 3T3 fibroblast cells transfected with the murine H-2K(k) or H-2D(k) genes, and only the H-2K(k) transfectants were lysed by PfCSP TCL.1 after incubation with peptide PfCSP 7G8 375-383. Binding to H-2K(k) was confirmed by competitive inhibition of binding of labelled peptides to affinity-purified K-k molecules. Substitution of the anchor amino acid residue, E, at position 2 with A dramatically reduced binding to K-k and eliminated the capacity of the peptide to sensitize target cells for killing. Variation of non-anchor residues did not markedly reduce binding to K-k but in some cases eliminated the capacity of the peptide to sensitize targets for cytolysis by PfCSP TCL.1, presumably by eliminating T-cell receptor-binding sites. These data suggest that similar studies with human T cells will be required for optimal development of peptide-based vaccines designed to produce protective class I-restricted CD8(+) CTL against the PfCSP in humans. C1 USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. UNIV LAUSANNE,INST BIOCHEM,CH-1066 EPALINGES,SWITZERLAND. UNIV COPENHAGEN,INST MED MICROBIOL & IMMUNOL,COPENHAGEN,DENMARK. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20814. RI Buus, Soren/F-5446-2010 NR 40 TC 8 Z9 8 U1 0 U2 1 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 MAY PY 1995 VL 63 IS 5 BP 1955 EP 1959 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QU941 UT WOS:A1995QU94100050 PM 7537251 ER PT J AU TANG, J TOE, L BACK, C ZIMMERMAN, PA PRUESS, K UNNASCH, TR AF TANG, J TOE, L BACK, C ZIMMERMAN, PA PRUESS, K UNNASCH, TR TI THE SIMULIUM-DAMNOSUM SPECIES COMPLEX - PHYLOGENETIC ANALYSIS AND MOLECULAR-IDENTIFICATION BASED UPON MITOCHONDRIALLY ENCODED GENE-SEQUENCES SO INSECT MOLECULAR BIOLOGY LA English DT Article DE SIMULIUM DAMNOSUM SL; DIRECTED HETERODUPLEX ANALYSIS; MITOCHONDRIAL DNA; PHYLOGENY ID ONCHOCERCIASIS CONTROL PROGRAM; BLACK FLIES DIPTERA; DNA; VOLVULUS; DIFFERENTIATION; PARASITE; MEMBERS; AFRICA; FOREST AB The DNA sequence of portions of the 16s rRNA and the NADH dehydrogenase subunit 4 (ND4) genes were used to determine phylogenetic relationships in the Simulium damnosum s.l. species complex. Results suggested that at least two major clades existed in the S. damnosum species complex, and that members of the S. damnosum s.l, species complex were not closely related to North American Simulium species. The sequence variability of the ND4 gene was exploited to develop a method to distinguish the sibling species of the S. damnosum s.l. species complex, based on directed heteroduplex analysis of PCR products derived from the ND4 gene. This method was capable of classifying the six sibling species into at least five groups. C1 UNIV ALABAMA,DIV GEOG MED,BIRMINGHAM,AL 35294. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV NEBRASKA,DEPT ENTOMOL,LINCOLN,NE 68583. ONCHOCERCIASIS CONTROL PROGRAM,BOUAKE,COTE IVOIRE. OI Tang, Jianming/0000-0003-0137-7486 FU NIAID NIH HHS [AI 33008] NR 30 TC 43 Z9 46 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD MAY PY 1995 VL 4 IS 2 BP 79 EP 88 DI 10.1111/j.1365-2583.1995.tb00011.x PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA RH520 UT WOS:A1995RH52000002 PM 7551196 ER PT J AU LANZARO, GC ZHENG, L TOURE, YT TRAORE, SF KAFATOS, FC VERNICK, KD AF LANZARO, GC ZHENG, L TOURE, YT TRAORE, SF KAFATOS, FC VERNICK, KD TI MICROSATELLITE DNA AND ISOZYME VARIABILITY IN A WEST-AFRICAN POPULATION OF ANOPHELES-GAMBIAE SO INSECT MOLECULAR BIOLOGY LA English DT Article DE MICROSATELLITE DNA; ISOZYMES; POPULATION GENETICS; AN GAMBIAE ID POLYMERASE CHAIN-REACTION; MALARIA VECTOR; MOSQUITO; GENE; AMPLIFICATION; POLYMORPHISMS; SPECIATION; CULICIDAE; ALLELES; MARKERS AB Microsatellites are defined as tracts of tandemly repeated short DNA sequences, Polymorphisms in this class of DNA are currently being used to generate a genetic map of the mosquito Anopheles gambiae. In the present study we explore the potential of microsatellites as a tool for studying the genetic structure of natural populations of this malaria vector. Genetic polymorphism at twenty enzyme coding gene loci and eleven microsatellite DNA loci was surveyed in a population of An. gambiae from Mall, West Africa, All of the microsatellite loci surveyed were polymorphic, as compared to 40% of the isozyme loci. The mean heterozygosity for the isozyme loci was only 0.097 (+/- 0.0035), but for the microsatellite loci it was 0.732 (+/- 0.060). The pattern of variability was very different between isozymes and microsatellites. Typically, at an isozyme locus a single allele occurred at a frequency greater than or equal to 0.75, whereas at microsatellite loci the most common allele had a frequency < 0.50. We conclude that microsatellites provide a rich source of genetic polymorphisms for the study of the population genetics of An. gambiae and are in many ways superior to isozymes for this purpose, We discuss the potential for utilizing genetically mapped microsatellite loci to explore the effect of chromosomal inversions on the distribution of genetic polymorphisms in An. gambiae. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HARVARD UNIV,BIOL LABS,CAMBRIDGE,MA 02138. NATL SCH MED & PHARM,MALARIA RES & TRAINING CTR,BAMAKO,MALI. NR 38 TC 78 Z9 80 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD MAY PY 1995 VL 4 IS 2 BP 105 EP 112 DI 10.1111/j.1365-2583.1995.tb00014.x PG 8 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA RH520 UT WOS:A1995RH52000005 PM 7551192 ER PT J AU MAYS, TD MAZAN, KD AF MAYS, TD MAZAN, KD TI THE BALANCE OF INTERESTS IN NATURAL-PRODUCTS DEVELOPMENT THE NATIONAL CANCER INSTITUTES LETTER OF COLLECTION SO INTERCIENCIA LA English DT Article DE NATURAL PRODUCTS PROGRAM; NATIONAL CANCER INSTITUTE ID ANTITUMOR AB With the advent of improved screening techniques, the use of natural products in the treatment for cancer and AIDS holds greater promise than ever and has resulted in a rejuvenation of the National Cancer Institute's Natural Products program. Plant materials have been collected by contractors on behalf of NCl from tropical and subtropical regions of Africa and Madagascar, Central and South America and Southeast Asia. Marine organisms, fungi, cyanbacteria and marine anaerobic bacteria and other protists have been collected mainly from the Indo-Pacific region. Through the participation of these countries in the collections program and the use of the improved screening techniques, the National Cancer Institute believes that the Natural Products Program may hold the best hope for the identification and development of new agents for the treatment of both cancer and AIDS. However, the realization of that promise lies in the Institute's ability to balance a series of competing interests in a manner that is constructive to the concerns of indigenous peoples and source countries as well as the U. S. government's interests and those of the private sector. The National Cancer Institute, like all agencies of the U.S. government, has a statutory mission to promote the commercial development of inventions developed directly by the agency or through funding provided by the agency. Furthermore, NCI operates under the national policy to use the patent system federally supported research to the domestic private sector. Although this has improved commercial development of NCI's inventions by industry, the primary reliance on the patent system to transfer the technology presents a unique problem in the development of natural products collected from source countries. Specifically, under current U. S. patent law, only a natural person (not an organization, group or country) who makes a material contribution to a claimed invention qualifies to be an inventor. Therefore, source countries and indigenous populations generally are not recognized as inventors and do not enjoy benefits as inventors from the intellectual property rights that arise from the natural products to which they have provided access. Thus, the patent system provides no means to compensate the source countries and indigenous populations for their often valuable contributions. As the developing world is quickly becoming aware of the economic value of its native biological diversity, there is growing concern over the inability to recognize significant contributions of source countries and indigenous populations to the drug discovery process. If mechanisms to recognize their contribution are not identified, there may be little incentive for source countries to preserve their biodiversity for drug discovery, or to provide access to that biodiversity for the purposes of drug discovery. This had led to the exploration of other legal instruments to achieve equity in the treatment of all parties to a natural product drug discovery program. Several legal instruments are being used, or proposed, to achieve what current patent law cannot. The alternatives range from the use of contracts, trusts and other fiduciary mechanisms, to the creative use of licensing agreements. C1 NCI,OFF TECHNOL DEV,NAT PROD UNIT,BETHESDA,MD 20892. RP MAYS, TD (reprint author), NCI,OFF TECHNOL DEV,BLDG 31,ROOM 4A5U,900 ROCHVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 1 U2 2 PU INTERCIENCIA PI CARACAS PA APARTADO 51842, CARACAS 1050A, VENEZUELA SN 0378-1844 J9 INTERCIENCIA JI Interciencia PD MAY-JUN PY 1995 VL 20 IS 3 BP 130 EP 133 PG 4 WC Ecology SC Environmental Sciences & Ecology GA RB693 UT WOS:A1995RB69300005 ER PT J AU METCALFE, DD AF METCALFE, DD TI INTERACTION OF MAST-CELLS WITH EXTRACELLULAR-MATRIX PROTEINS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE MAST CELLS; INTEGRINS; ALLERGY; FIBRONECTIN; LAMININ; VITRONECTIN; MATRIX; IGE ID TYROSINE PHOSPHORYLATION; LAMININ; FIBRONECTIN; ADHERENCE; AGGREGATION; ATTACHMENT; RECEPTORS; ADHESION AB It is possible to divide surface receptors on mast cells conceptually into three groups. The first consists of immune response receptors. The index receptor for this group is Fc epsilon RI, now joined by Fc gamma receptors and receptors for complement products. The second group of receptors are those that are involved in growth and differentiation, such as those for interleukin-3 and stem cell factor. The third group consists of receptors regulating mast cell trafficking and distribution. Principle among the latter group of receptors are those that engage extracellular matrix components, including the classical integrin receptors. The engagement of mast cells to matrix components not only has relevance in determining the tissue distribution of mast cells, but also appears to have a major influence on the biologic responsiveness of mast cells to immune- and growth-factor-receptor-mediated signals. RP METCALFE, DD (reprint author), NIAID,CLIN INVEST LAB,ALLERG DIS SECT,9000 ROCKVILLE PIKE, BLDG 10,ROOM 11C205,BETHESDA,MD 20892, USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 60 EP 62 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100015 PM 7542103 ER PT J AU MEKORI, YA OH, CK METCALFE, DD AF MEKORI, YA OH, CK METCALFE, DD TI THE ROLE OF C-KIT AND ITS LIGAND, STEM-CELL FACTOR, IN MAST-CELL APOPTOSIS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE MAST CELLS; APOPTOSIS; C-KIT; C-KIT LIGAND; STEM CELL FACTOR ID RECEPTOR; GROWTH AB The regulation of tissue mast cell number depends both on the rate of production of mast cell precursors and the length of survival of mature mast cells within tissues. Once mast cell precursors target to tissues, their survival may largely be dependent upon the local production of stem cell factor (SCF). Withdrawal of interleukin (IL)-3 results in mast cell apoptosis. The apoptotic changes following IL-3 deprivation are prevented by the addition of SCF which exerts its rescue effect upon interaction with its c-Kit tyrosine kinase receptor. Mast cells undergo apoptosis on withdrawal of IL-3 coincident with a decrease in endogenous bcl-2 mRNA; however, SCF does not induce expression of bcl-2 when added to these cells. When overexpressed, bcl-2 prolongs survival of bcl-2-transfected mast cells following IL-3 deprivation. Transforming growth factor-beta was found to specifically prevent this SCF-mediated rescue from apoptosis, probably by downregulating the expression of c-Kit. Thus, microenvironmental factors play an important role in regulating mast cell numbers by effecting survival in the periphery. C1 MEIR HOSP,DEPT MED,ALLERGY CLIN IMMUNOL UNIT,IL-44281 KEFAR SAVA,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. NR 15 TC 37 Z9 38 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 136 EP 138 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100039 PM 7542059 ER PT J AU GERGEN, PJ GOLDSTEIN, RA AF GERGEN, PJ GOLDSTEIN, RA TI DOES ASTHMA EDUCATION EQUAL ASTHMA INTERVENTION SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE ASTHMA; EDUCATION; INTERVENTION; MORBIDITY; TREATMENT ID MORBIDITY; TRIAL AB The complex, multifactorial problem of increasing asthma morbidity, especially in minority communities, will not be solved by unidimensional approaches. Appropriately targeted multidimensional intervention programs are needed to control the rising burden of asthma. RP GERGEN, PJ (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,OFF EPIDEMIOL & CLIN TRIALS,SOLAR BLDG,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 166 EP 168 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100050 PM 7613124 ER PT J AU SUGIE, K NAKAMURA, K TESHIGAWARA, K DIAMOND, MS SPRINGER, TA NAKAMURA, Y LEONARD, WJ UCHIDA, A YODOI, J AF SUGIE, K NAKAMURA, K TESHIGAWARA, K DIAMOND, MS SPRINGER, TA NAKAMURA, Y LEONARD, WJ UCHIDA, A YODOI, J TI ACTIVATION OF NATURAL-KILLER-CELLS BY THE MAB YTA-1 THAT RECOGNIZES LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE LFA-1; NATURAL KILLER; YT CELL LINE ID LARGE GRANULAR LYMPHOCYTES; T-CELLS; MONOCLONAL-ANTIBODY; ALPHA-SUBUNIT; INTERLEUKIN-2 RECEPTOR; ADHESION GLYCOPROTEIN; COUNTER-RECEPTOR; NK CLONES; INTEGRIN; MOLECULES AB The mAb YTA-1, which brightly stains CD3(-)CD16(+) large granular lymphocytes (LGL)/natural killer (NK) cells and CD8(+) T cells by immunofluorescence, is specific for leukocyte function-associated antigen (LFA)-1. Some mAbs recognizing the LFA-1 alpha chain (CD11a) or LFA-1 beta chain (CD18) inhibited the binding of YTA-1 to peripheral blood mononuclear cells, YTA-1 mAb could be chemically cross-linked to 170 and 96 kDa molecules, whose molecular weights correspond to those of LFA-1 alpha and beta respectively, YTA-1 bound to COS-7 cells co-transfected with CD11a and CD18 cDNAs, but not to untransfected cells, Reactivities of YTA-1 to K562 cells transfected with LFA-1 alpha and beta (CD11a/CD18) cDNAs and to CHO cells transfected with Mac-1 (CD11b/CD18) or p150, 95 (CD11c/CD18) cDNAs strongly suggest that YTA-1 recognizes either LFA-1 alpha or an epitope formed by a combination of LFA-1 alpha and beta. Treatment of fresh CD3(-)CD16(+) LGL with YTA-1 augmented cytolytic activity and induced proliferation. F(ab')(2) fragments of YTA-1 augmented NK cytotoxicity, indicating that the NK activating signal was transmitted through LFA-1 without involvement of Fc gamma receptor III, In contrast, the other mAbs against LFA-1 could not activate NK cells. These results collectively indicate that YTA-1 recognizes a unique epitope of LFA-1, which is involved in activation of fresh NK cells. C1 KYOTO UNIV,CTR RADIAT BIOL,DEPT LATE EFFECT STUDIES,SAKYO KU,KYOTO 60601,JAPAN. KYOTO UNIV,INST VIRUS RES,DEPT BIOL RESPONSES,SAKYO KU,KYOTO 60601,JAPAN. KYOTO UNIV,CHEST DIS RES INST,DEPT IMMUNOL,SAKYO KU,KYOTO 60601,JAPAN. HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,BOSTON,MA 02115. NHLBI,IRP,OD,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 34 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1995 VL 7 IS 5 BP 763 EP 769 PG 7 WC Immunology SC Immunology GA QZ064 UT WOS:A1995QZ06400006 PM 7547703 ER PT J AU LARSON, DE RISING, R FERRARO, RT RAVUSSIN, E AF LARSON, DE RISING, R FERRARO, RT RAVUSSIN, E TI SPONTANEOUS OVERFEEDING WITH A CAFETERIA DIET IN MEN - EFFECTS ON 24-HOUR ENERGY-EXPENDITURE AND SUBSTRATE OXIDATION SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE OVERFEEDING; CAFETERIA DIET; ENERGY EXPENDITURE; SUBSTRATE OXIDATION ID FOOD-INTAKE; FAT OXIDATION; PIMA-INDIANS; WEIGHT-GAIN; CARBOHYDRATE; OBESITY; HUMANS; BALANCE; LIPOGENESIS; EXERCISE AB OBJECTIVE: To investigate the relationship between obesity and ad librtum food intake (quantity and composition) and to assess the impact of ad libitum food intake on energy expenditure and macronutrient oxidation. DESIGN: Mate volunteers were first fed a weight maintaining diet for at least 4 days before selecting their food for the next 5 days from two computerized vending machines offering a variety of familiar, palatable foods, 24-h energy expenditure (24EE) and substrate oxidation were measured in a respiratory chamber on the last day of each weight maintenance and ad libitum intake periods. SETTING: Ten day admission on a metabolic research ward. SUBJECTS: Thirty-four non-diabetic Pima Indian males covering a wide range of body weight and body composition (30 +/- 8 y, 102.1 +/- 30.2 kg, 34 +/- 9% body fat, mean +/- s.d.). RESULTS: Weight maintenance requirements averaged 2913 +/- 342 kcal/d, Energy intake during the ad libitum period increased to 4550 +/- 921 kcal/d (12 +/- 1% protein, 40 +/- 4% fat, 48 +/- 4% carbohydrate) i.e., a spontaneous overeating by 54 +/- 32% above weight maintenance requirement, resulting in a 0.9 +/- 1.0 kg body weight gain. Neither the composition of the selected diet nor the degree of overeating was associated with physical characteristics, such as body weight and body composition, When compared with baseline, spontaneous overeating on day 5 was associated with a 396 +/- 233 kcal/d increase in 24EE, a 607 +/- 503 kcal/d increase in carbohydrate oxidation, a 214 +/- 392 kcal/d decrease in lipid oxidation (P < 0.01), and no change in protein oxidation. Increased carbohydrate oxidation correlated with the excess carbohydrate intake (r = 0.69, p = 0.0001) accounting for 68 +/- 13% (mean +/- s.e.e) of the excess, whereas excess fat intake was not oxidized. CONCLUSION: In response to spontaneous overfeeding on a mixed 'cafeteria diet', excess carbohydrate intake is oxidized, suggesting a physiological control of carbohydrate stores, whereas excess fat intake is channeled toward fat stores, None of the observed changes were related to indices of obesity. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 40 TC 24 Z9 25 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 1995 VL 19 IS 5 BP 331 EP 337 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA QW723 UT WOS:A1995QW72300007 PM 7647825 ER PT J AU ZHAN, QM ELDEIRY, W BAE, I ALAMO, I KASTAN, MB VOGELSTEIN, B FORNACE, AJ AF ZHAN, QM ELDEIRY, W BAE, I ALAMO, I KASTAN, MB VOGELSTEIN, B FORNACE, AJ TI SIMILARITY OF THE DNA-DAMAGE RESPONSIVENESS AND GROWTH-SUPPRESSIVE PROPERTIES OF WAF1/CIP1 AND GADD45 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MDM2; IONIZING RADIATION; P53; DNA DAMAGE; CAFFEINE; ULTRAVIOLET RADIATION; METHYLMETHANE SULFONATE ID CELL-CYCLE; P53 PROTEIN; AGENTS; GENE; INDUCTION; ARREST; RNA; ACTIVATION; RADIATION; BINDING AB The cellular responses to genotoxic stress are complex involving both p53-dependent and independent mechanisms. In the case of the GADD genes, many stresses eliciting growth arrest have been shown to induce these genes in a coordinate fashion regardless of p53 status, while the ionizing radiation response (IR) of GADD45 has been found to be strictly p53-dependent. In the current study, the response of GADD45 was compared to the p53-regulated genes WAF1/CIP1 and MDM2 in a panel of human lines with known p53 status and also in mouse embryo fibroblasts where one or both alleles of p53 had been deleted. After IR, all 3 genes showed very similar transcriptional responses as measured by rapid increases in mRNA. in a p53-dependent manner. Like GADD45, the WAF1/CIP1 induction by IR can be enhanced by the radiosensitizer iododeoxyuridine, and provides further evidence that DNA strand breaks can act as a signal for activation of the p53 pathway. In addition, caffeine, which blocks IR cell-cycle checkpoint activation, reduced IR induction for both genes. Unlike the case for IR, only WAF1/CIP1 showed a consistent similarity to GADD45 to DNA base-damaging agents, where appreciable induction occurred in cells regardless of p53 status. The similarity between WAF1/CIP1 and GADD45 also extended to their growth suppressive properties, and a combination of expression vectors for these genes suppressed growth appreciably more than either alone. A reasonable interpretation of these results is that growth suppression after DNA damage by either p53-dependent or independent pathways is mediated by the combined action of multiple downstream effecters including WAF1/CIP1 and GADD45. C1 JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21287. RP ZHAN, QM (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 42 TC 46 Z9 46 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1995 VL 6 IS 5 BP 937 EP 946 PG 10 WC Oncology SC Oncology GA QV964 UT WOS:A1995QV96400002 PM 21556622 ER PT J AU NEWTON, SA REEVES, EJ GRALNICK, H MOHLA, S YAMADA, KM OLDEN, K AKIYAMA, SK AF NEWTON, SA REEVES, EJ GRALNICK, H MOHLA, S YAMADA, KM OLDEN, K AKIYAMA, SK TI INHIBITION OF EXPERIMENTAL METASTASIS OF HUMAN BREAST-CARCINOMA CELLS IN ATHYMIC NUDE-MICE BY ANTI-ALPHA(5)BETA(1) FIBRONECTIN RECEPTOR INTEGRIN ANTIBODIES SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE BREAST CARCINOMA; FIBRONECTIN RECEPTOR; INTEGRIN ANTIBODIES ID MURINE MELANOMA-CELLS; ALPHA-IIB-BETA-3 INTEGRIN; MALIGNANT TRANSFORMATION; ADHESION MOLECULES; CANCER METASTASIS; ENDOTHELIAL-CELLS; TUMOR-METASTASIS; LAMININ RECEPTOR; EXPRESSION; PROTEIN AB We have investigated the role of the human alpha(5) beta(1) fibronectin receptor integrin in experimental metastasis. Treatment of human MDA-MB-231 breast carcinoma cells with monoclonal antibodies specific for alpha(5) or beta(1) integrin subunits prior to injection into the tail veins of 7 to 9 week old athymic nude mice significantly decreased the median number of lung colonies that were formed. In contrast, treatment of the cells with monoclonal antibodies specific for the alpha(2) subunit had no significant effect. In vitro, the anti-alpha(5) and the anti-beta(1) monoclonal antibodies both strongly inhibited breast carcinoma cell adhesion to fibronectin, while only the anti-beta(1) monoclonal antibody inhibited adhesion to laminin. In a Boyden chamber invasion assay, the anti-beta(1) antibody almost completely inhibited invasion of the breast carcinoma cells through an artificial Matrigel basement membrane. The anti-alpha(5) monoclonal antibody inhibited in vitro invasion approximately 30%, only if fibroblast conditioned medium was present as a chemoattractant. Cell migration on fibronectin could be inhibited by both the anti-alpha(5) and the anti-beta(1) monoclonal antibody. These results indicate that the alpha(5) beta(1) integrin fibronectin receptor on MDA-MB-231 human breast carcinoma cells plays an important role in experimental hematogenous metastasis and may function in this process by a combination of mechanisms, including tumor cell attachment to fibronectin and fibronectin-directed extravasation of tumor cells into the target organ. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,CTR CANC,WASHINGTON,DC 20060. NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. NR 51 TC 16 Z9 16 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1995 VL 6 IS 5 BP 1063 EP 1070 PG 8 WC Oncology SC Oncology GA QV964 UT WOS:A1995QV96400021 PM 21556641 ER PT J AU TAMANO, S JAKUBCZAK, J TAKAGI, H MERLINO, G WARD, JM AF TAMANO, S JAKUBCZAK, J TAKAGI, H MERLINO, G WARD, JM TI INCREASED SUSCEPTIBILITY TO N-NITROSOMETHYLUREA GASTRIC CARCINOGENESIS IN TRANSFORMING GROWTH-FACTOR-ALPHA TRANSGENIC MICE WITH GASTRIC HYPERPLASIA SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE N-NITROSOMETHYLUREA; GLANDULAR STOMACH CARCINOMA; TRANSGENIC MOUSE; TRANSFORMING GROWTH FACTOR ALPHA ID TGF-ALPHA; IMMUNOHISTOCHEMICAL DEMONSTRATION; PYLORIC GLANDS; MOUSE MODEL; C-MYC; INDUCTION; LIVER; PEPSINOGEN; STOMACH; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE AB Glandular stomach carcinogenesis after N-nitrosomethylurea (NMU) treatment was examined in transgenic mice bearing a human transforming growth factor alpha (TGF-alpha) cDNA driven by the mouse metallothionein-I promoter (mouse line MT100) in the inbred mouse line FVB/N. Untreated MT100 mice exhibit a severe age-related gastric fundic hyperplasia. Both sexes of MT100 mice were given 10 weekly intragastric intubations of 0.5 mg NMU per mouse from 6 weeks of age and/or zinc chloride in drinking water to stimulate transgene expression from 5.5 weeks of age to the experiment termination. Animals were killed sequentially at 10, 19 and 29 experimental weeks. Several histochemical markers (AB-PAS, TGF-alpha, pepsinogen isozyme 1, proliferating cell nuclear antigen) were used. Abnormal histochemical patterns were found in untreated MT100 and NMU-treated MT100 mice for all 4 markers of differentiation and carcinogenesis. Precancerous lesions including atypical and/or adenomatous hyperplasia were found in the fundic region of 16/22 male and 8/22 female MT100 mice but not in 27 male and 24 female FVB/N mice treated with NMU. One of 22 MT100 males had fundic carcinoma. FVB/N mice treated with NMU had neither precancerous lesions nor carcinomas in the fundus. Well differentiated adenocarcinomas in the pyloric region were induced at incidences of 2/22 male and 1/22 female MT100 mice treated with NMU and 4/27 male and 4/24 female FVB/N mice treated with NMU. Both strains also had a high incidence (55 to 92%) of squamous cell carcinomas of the forestomach, In conclusion, TGF-alpha induced a hyperplastic lesion in the gastric fundus that appeared to predispose the MT100 mice to carcinogenesis by NMU. C1 NCI,FREDERICK CANC RES & DEV CTR,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [1-CO-74102] NR 32 TC 16 Z9 16 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD MAY PY 1995 VL 86 IS 5 BP 435 EP 443 PG 9 WC Oncology SC Oncology GA RA614 UT WOS:A1995RA61400005 PM 7790317 ER PT J AU FIGUEROA, JP MORRIS, J BRATHWAITE, A WARD, E PERUGA, A HAYES, R VERMUND, SH BLATTNER, W AF FIGUEROA, JP MORRIS, J BRATHWAITE, A WARD, E PERUGA, A HAYES, R VERMUND, SH BLATTNER, W TI RISK-FACTORS FOR HTLV-I AMONG HETEROSEXUAL STD CLINIC ATTENDERS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE I; SEXUALLY TRANSMITTED DISEASE; RISK FACTORS; HETEROSEXUAL TRANSMISSION; JAMAICA ID VIRUS TYPE-I; CELL LEUKEMIA-VIRUS; SEXUAL TRANSMISSION; HEPATITIS-B; SEROPREVALENCE; JAPAN; DETERMINANTS; SUPPRESSION; INFECTION; ANTIBODY AB Human T-cell lymphotropic virus type 1 (HTLV-1) status was assessed in 994 patients attending a sexually transmitted disease (STD) clinic in Kingston, Jamaica, between November 1990 and January 1991 for a new STD complaint, Of 515 heterosexual men, 36 (7.0%) were HTLV-1 seropositive, as were 38 (7.9%) of 479 women. HTLV-1 seroprevalence increased with age in women. A history of blood transfusion was associated with HTLV-1 in both sexes, significantly so in men [odds ratio (OR) 4.7, confidence interval (CI) 1.1-17 for men; OR 1.9, CI 0.6-5.0 for women]. Further analysis excluded all persons reporting a transfusion. On multiple logistic regression analysis, independent associations with HTLV-1 infection in men were shown for marital status (OR 3.5, CI 1.2-10 for married/common law vs, single/visiting unions), agricultural occupation (OR 9.0, CI 2.0-41), bruising during sex (OR 2.9, CI 1.0-8.1), greater than or equal to 15 years at first sexual intercourse (OR 2.9, CI 1.0-8.2), and a positive test for hepatitis B surface antigen (OR 7.3, CI 1.2-52). In women, associations were shown for two or more sex partners in the 4 weeks prior to complaint (OR 4.9, CI 1.8-13), 11 or more lifetime sexual partners (OR 5.9, CI 1.3-27), aged <15 years at first sexual intercourse (OR 2.3, 1.0-5.4), bruising during sex (OR 2.7, CI 1.1-6.6), microhaemagglutination-Treponema pallidum positivity (OR 3.6, CI 1.6-8.4), and human immunodeficiency virus infection (OR 14, CI 2.1-92). STDs and bruising during sex may facilitate sexual transmission of HTLV-1, whereas sexual activity is a more important risk factor in women than men. Programs promoting safer sexual practices and controlling STDs may reduce HTLV-1 infection in Jamaica. C1 LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. PANAMER HLTH ORG,WASHINGTON,DC. NIAID,DIV AIDS,BETHESDA,MD 20892. NATL CANC INST,BETHESDA,MD. RP FIGUEROA, JP (reprint author), MINIST HLTH,EPIDEMIOL UNIT,30-34 HALF WAY TREE RD,KINGSTON 5,JAMAICA. OI Hayes, Richard/0000-0002-1729-9892; Vermund, Sten/0000-0001-7289-8698 NR 26 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1995 VL 9 IS 1 BP 81 EP 88 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QV577 UT WOS:A1995QV57700012 PM 7712238 ER PT J AU CONE, EJ AF CONE, EJ TI COMPARISON OF URINE AND HAIR TESTING FOR DRUGS OF ABUSE - REPLY SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter ID IDENTIFICATION RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,LEXINGTON,KY 40583, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD MAY-JUN PY 1995 VL 19 IS 3 BP 203 EP 204 PG 2 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA QX913 UT WOS:A1995QX91300015 ER PT J AU THOMPSON, J GENTRYWEEKS, CR NGUYEN, NY FOLK, JE ROBRISH, SA AF THOMPSON, J GENTRYWEEKS, CR NGUYEN, NY FOLK, JE ROBRISH, SA TI PURIFICATION FROM FUSOBACTERIUM-MORTIFERUM ATCC-25557 OF A 6-PHOSPHORYL-O-ALPHA-D-GLUCOPYRANOSYL-6-PHOSPHOGLUCOHYDROLASE THAT HYDROLYZES MALTOSE 6-PHOSPHATE AND RELATED PHOSPHO-ALPHA-D-GLUCOSIDES SO JOURNAL OF BACTERIOLOGY LA English DT Article ID D-PHOSPHOGALACTOSIDE GALACTOHYDROLASE; SUGAR PHOSPHOTRANSFERASE SYSTEM; BETA-GALACTOSIDASE GENE; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI K12; NUCLEOTIDE-SEQUENCE; SUCROSE-6-PHOSPHATE HYDROLASE; STREPTOCOCCUS-MUTANS; BACILLUS-SUBTILIS; BGL OPERON AB 6-Phospholyl-O-alpha-D-glucopyranosyl:6-phosphoglucohydrolase (8-phospho-alpha-glucosidase) has been purified from Fusobacterium mortiferum ATCC 25557, p-Nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alpha Glc6P) served as the chromogenic substrate for detection and assay of enzyme activity, The O-2-sensitive, metal-dependent phospho-alpha-glucosidase was stabilized during purification by inclusion of dithiothreitol and Mn2+ ion in chromatography buffers. Various 6-phosphoryl-O-alpha-linked glucosides, including maltose 6-phosphate, pNP alpha Glc6P, trehalose 6-phosphate, and sucrose 6-phosphate, mere hydrolyzed by the enzyme to yield D-glucose 6-phosphate and aglycone moieties in a 1:1 molar ratio, 6-Phospho-alpha-glucosidase (M(r) of similar to 49,000; pI of similar to 4.9) is activated by Fe2+, Mn2+, Co2+, and Ni2+, and the maximum rate of pNP alpha Glc6P hydrolysis occurs at 40 degrees C within the pH range 7.0 to 7.5, The sequence of the first 32 amino acids of 6-phospho-alpha-glucdsidase exhibits 67% identity (90% similarity) to that deduced for the N terminus of a putative phospho-beta-glucosidase (designated ORF f212) encoded by glvG in Escherichia coli. Western blots involving highly specific polyclonal antibody against 6-phospho-alpha-glucosidase and spectrophotometric analyses with pNP alpha Glc6P revealed only low levels of the enzyme in glucose-, mannose-, or fructose-grown cells of F. mortiferum, Synthesis of 6-phospho-alpha-glucosidase increased dramatically during growth of the organism on alpha-glucosides, such as maltose, alpha-methylglucoside, trehalose, turanose, and palatinose. C1 NIDR, CELLULAR DEV & ONCOL LAB, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. RP THOMPSON, J (reprint author), NIDR, MICROBIAL ECOL LAB, BLDG 30, RM 528, BETHESDA, MD 20892 USA. NR 53 TC 33 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1995 VL 177 IS 9 BP 2505 EP 2512 PG 8 WC Microbiology SC Microbiology GA QW529 UT WOS:A1995QW52900036 PM 7730284 ER PT J AU COURT, DL PATTERSON, TA BAKER, T COSTANTINO, N MAO, XH FRIEDMAN, DI AF COURT, DL PATTERSON, TA BAKER, T COSTANTINO, N MAO, XH FRIEDMAN, DI TI STRUCTURAL AND FUNCTIONAL ANALYSES OF THE TRANSCRIPTION-TRANSLATION PROTEINS NUSB AND NUSE SO JOURNAL OF BACTERIOLOGY LA English DT Note ID ESCHERICHIA-COLI; PHAGE-LAMBDA; BACTERIOPHAGE-LAMBDA; SECY24 MUTATION; RNA-POLYMERASE; GENE; ANTITERMINATION; SEQUENCE; TERMINATION; RECOGNITION AB The NusB and NusE (ribosomal protein S10) proteins function in transcription and translation. The two proteins form a complex that binds to the boxA sequence found in the leader RNA of rm operons; boxA is required for transcription antitermination in rrn operons. Although binding of these two proteins to the boxA RNA of the bacteriophage lambda nut site has not been observed, both NusB and NusE as well as the RNA boxA sequence are required for lambda N-mediated antitermination. Studies identifying the amino acid changes caused by mutations in nusB and nusE and relating these changes to altered function are reported. It is concluded that boxA is essential for an effective NusB contribution to N-mediated antitermination and that by mutation NusB may be changed to allow more-effective binding to boxA variants. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. RP COURT, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702, USA. RI Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 FU NCI NIH HHS [N0-CO-46000]; NCRR NIH HHS [MO-RR00042]; NIAID NIH HHS [AI11459-10] NR 23 TC 27 Z9 27 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 MAY PY 1995 VL 177 IS 9 BP 2589 EP 2591 PG 3 WC Microbiology SC Microbiology GA QW529 UT WOS:A1995QW52900049 PM 7730297 ER PT J AU MERKEL, TJ STIBITZ, S AF MERKEL, TJ STIBITZ, S TI IDENTIFICATION OF A LOCUS REQUIRED FOR THE REGULATION OF BVG-REPRESSED GENES IN BORDETELLA-PERTUSSIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; VIRULENCE FACTORS; ESCHERICHIA-COLI; CHROMOSOMAL INSERTION; NUCLEOTIDE-SEQUENCE; MERCURIC-RESISTANCE; CLONING SYSTEM; VIR; DNA; CONSTRUCTION AB In Bordetella pertussis, the coordinate regulation of virulence factor expression is controlled by the products of the bvgAS locus. In the presence of modulating signals such as MgSO4, nicotinic acid, or reduced temperature, the expression of bvg-activated genes is reduced while the expression of bvg-repressed genes is induced. One model for the regulation of bvg-repressed genes predicts the existence of a repressor protein encoded by a bvg-activated gene, Once activated, the product of this bvg-activated gene would bind to and repress transcription from the bvg-repressed genes. We isolated five genetically independent transposon insertion mutants of B. pertussis that have a phenotype consistent,vith the knockout of a putative bvg-regulated repressor. These mutants constitutively expressed a vrg6-phoA transcriptional fusion but demonstrated normal bvgAS function. Genomic mapping and DNA sequence analysis of the sites of transposon insertion demonstrated that these mutants define a locus downstream of bvgAS. Introduction of an in-frame, 12-bp insertion within this locus also conferred the mutant phenotype, confirming that the phenotype seen in the transposon mutants is the result of disruption of a distinct gene, which we have designated bvgR, and is not a consequence of polar effects on bvgAS. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP MERKEL, TJ (reprint author), NIDR,LME,BLDG 30,RM 532,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 46 Z9 48 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 MAY PY 1995 VL 177 IS 10 BP 2727 EP 2736 PG 10 WC Microbiology SC Microbiology GA QX752 UT WOS:A1995QX75200016 PM 7751282 ER PT J AU KULAEVA, OI WOOTTON, JC LEVINE, AS WOODGATE, R AF KULAEVA, OI WOOTTON, JC LEVINE, AS WOODGATE, R TI CHARACTERIZATION OF THE UMU-COMPLEMENTING OPERON FROM R391 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM LT2; MUTAGENIC DNA-REPAIR; DIFFERENT INCOMPATIBILITY GROUPS; LIGHT-INDUCED MUTAGENESIS; ESCHERICHIA-COLI; RECA PROTEIN; SOS MUTAGENESIS; UV MUTAGENESIS; ULTRAVIOLET-LIGHT; SEQUENCE-ANALYSIS AB In addition to conferring resistances to antibiotics and heavy metals, certain R factors carry genes involved in mutagenic DNA repair. These plasmid encoded genes are structurally and functionally related to the chromosomally encoded umuDC genes of Escherichia coli and Salmonella typhimurium. Three such plasmid operons, mucAB, impCAB, and samAB, have been characterized at the molecular level. Recently, we have identified three additional umu-complementing operons from IncJ plasmid R391 and IncL/M plasmids R446b and R471a. We report here the molecular characterization of the R391 umu-complementing operon. The nucleotide sequence of the minimal R plasmid umu-complementing (rum) region revealed an operon of two genes, rumA((R391)) and rumB((R391), with an upstream regulatory signal strongly resembling LexA-binding sites. Phylogenetic analysis revealed that the RumAB((R391)) proteins are approximately equally diverged in sequence from the chromosomal UmuDC proteins and the other plasmid-encoded Umu-like proteins and represent a new subfamily. Genetic characterization of the rumAB((R391)) operon revealed that in recA(+) and recA1730 backgrounds, the rumAB((R391)) operon was phenotypically indistinguishable from mucAB. In contrast, however, the rumAB((R391)) operon gave levels of mutagenesis that were intermediate between those given by mucAB and umuDC in a recA430 strain. The latter phenotype was shown to correlate with the reduced posttranslational processing of the RumA((R391)) protein to its mutagenically active form, RumA'((R391)). Thus, the rumAB((R391)) operon appears to possess characteristics that are reminiscent of both chromosome and plasmid-encoded umu-like operons. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BETHESDA,MD 20892. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 59 TC 51 Z9 52 U1 0 U2 3 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 MAY PY 1995 VL 177 IS 10 BP 2737 EP 2743 PG 7 WC Microbiology SC Microbiology GA QX752 UT WOS:A1995QX75200017 PM 7751283 ER PT J AU CASJENS, S DELANGE, M LEY, HL ROSA, P HUANG, WM AF CASJENS, S DELANGE, M LEY, HL ROSA, P HUANG, WM TI LINEAR CHROMOSOMES OF LYME-DISEASE AGENT SPIROCHETES - GENETIC DIVERSITY AND CONVERSATION OF GENE ORDER SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACTERIUM BORRELIA-BURGDORFERI; SIGNATURE NUCLEOTIDE ANALYSIS; OUTER SURFACE-PROTEINS; RIBOSOMAL-RNA GENES; ESCHERICHIA-COLI; GEL-ELECTROPHORESIS; IXODES-PERSULCATUS; RELAPSING FEVER; SP-NOV; STRAINS AB We have constructed physical and genetic maps of the chromosomes of 21 Lyme disease agent spirochetes from geographically diverse locations. All have linear chromosomes whose lengths range from 935 to 955 kbp, and all contain multiple linear plasmids in the 16- to 175-kbp size range. The locations of 11 gene clusters on the chromosomes of these different isolates are indistinguishable at the resolution achieved in this study, indicating that the members of this related group of species have highly conserved chromosomal gene orders. However, chromosomal restriction endonuclease cleavage site maps are unique for nearly all isolates. The 22 chromosomal maps currently available define eight classes of Lyme disease agents. Four of these correspond to the previously proposed species Borrelia burgdorferi, Borrelia garinii, Borrelia afzelii, and Borrelia japonica, In addition, the North American isolates 21038, DN127 c19-2, 25015, and CA55 typify four additional chromo somal types that are as phylogenetically distinct as the species listed above. These findings support the idea that comparison of restriction maps is currently the most robust and definitive method for determining overall chromosomal relationships among closely related bacteria. In the course of this work, we located on the chromosome the previously unmapped outer surface protein encoding LA7 gene and genes homologous to the Escherichia coli priA, plsC, parE, and parC genes, and we have substantially refined the locations of the recA, fla, p22A, and flgE genes. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. RP CASJENS, S (reprint author), UNIV UTAH,MED CTR,DEPT ONCOL SCI,DIV MOLEC BIOL,SALT LAKE CITY,UT 84132, USA. FU NIGMS NIH HHS [GM21960] NR 87 TC 80 Z9 81 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1995 VL 177 IS 10 BP 2769 EP 2780 PG 12 WC Microbiology SC Microbiology GA QX752 UT WOS:A1995QX75200021 PM 7751287 ER PT J AU CARROLL, K WICKNER, RB AF CARROLL, K WICKNER, RB TI TRANSLATION AND M(1) DOUBLE-STRANDED-RNA PROPAGATION - MAK18=RPL41B AND CYCLOHEXIMIDE CURING SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 60S RIBOSOMAL-SUBUNITS; SACCHAROMYCES-CEREVISIAE; L-A; SUPERKILLER MUTATIONS; MESSENGER-RNA; PROTEIN L29; GAG-POL; YEAST; VIRUS; REPLICATION AB MAK18 is one of nearly 30 chromosomal genes of Saccharomyces cerevisiae necessary for propagation of the killer toxin-encoding M(1) double-stranded RNA satellite of the L-A double-stranded RNA virus. We have cloned and sequenced MGK18 and find that it is identical to RPL41B, one of the two genes encoding large ribosomal subunit protein L41. The mak18-1 mutant is deficient in 60S subunits, which we suggest results in a preferential decrease in translation of viral poly(A)-deficient mRNA. We have reexamined the curing of M, by low concentrations of cycloheximide (G. R. Fink and C. A. Styles, Proc. Natl. Acad. Sci. USA 69:2846-2849, 1972), which is known to act on ribosomal large subunit protein L29. We find that when M(1) is supported by L-A proteins made from the poly(A)(+) mRNA of a cDNA clone of L-A, cycloheximide does not decrease the M(1) copy number, consistent with our hypothesis. C1 NIDDKD,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. NR 46 TC 22 Z9 23 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 MAY PY 1995 VL 177 IS 10 BP 2887 EP 2891 PG 5 WC Microbiology SC Microbiology GA QX752 UT WOS:A1995QX75200036 PM 7751301 ER PT J AU FUJII, Y TOMIC, M STOJILKOVIC, SS IIDA, T BRANDI, ML OGINO, Y SAKAGUCHI, K AF FUJII, Y TOMIC, M STOJILKOVIC, SS IIDA, T BRANDI, ML OGINO, Y SAKAGUCHI, K TI EFFECTS OF ENDOTHELIN-1 ON CA2+ SIGNALING AND SECRETION IN PARATHYROID CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; PITUITARY GONADOTROPHS; NEUROENDOCRINE ACTIONS; CYTOSOLIC CALCIUM; RECEPTORS; EXPRESSION; CLONING; BOVINE; LINE; GLANDS AB It has been previously reported that parathyroid cells express endothelin (ET) receptors and secrete ET-1 in an extracellular Ca2+ concentration ([Ca2+](e))-dependent manner. Here, we examined the effects of ET-1 on intracellular signaling and parathyroid hormone (PTH) secretion in dispersed bovine parathyroid (bPT) cells, which comprise several cell types including epithelial and endothelial cells, in two cell lines, the rat parathyroid epithelial (PT-r) and the bovine parathyroid endothelial (BPE-1) cells. An RNA-polymerase chain reaction analysis revealed that both ET(A) and ET(B) receptors are expressed in bovine parathyroid tissue and BPE-1 cells, and only the ET(A) receptor is expressed in PT-r cells. PT-r cells also expressed an inositol 1,4,5-trisphosphate (Ins[1,4,5]P-3) receptor, and ionomycin induced an increase in the intracellular Ca2+ concentrations ([Ca2+](i)) in a Ca2+-deficient medium, indicating the presence of an operative intracellular Ca2+ pool in these cells. In cells bathed in 1 mM [Ca2+](e), ET-1 induced a rapid and transient increase in the Ins(1,4,5)P, production, which was associated with a similar profile of increase in [Ca2+](i) and with a peak response of about 800 nM. No changes in the profile of [Ca2+](i) responses were observed in ET-1-stimulated cells in the presence of Ca2+ channel blockers, or in Ca2+-deficient medium, indicating that Ca2+ mobilization was not associated with Ca2+ entry. Furthermore, a sustained stimulation with ET-1 induced a decrease in [Ca2+](i) below the prestimulatory level in a large population of cells, and the percentage of the cell population that shows the sustained decrease of [Ca2+](i) increased in higher ET-1 concentrations. [Ca2+](i) in PT-r cells was also controlled by a [Ca2+](i)-dependent mechanism that changed [Ca2+](i) from 28 to 506 nM in a 0.1-3 mM concentration range with an EC(50) of 1.2 mM, which is comparable to that reported for bPT cells. In the same range of [Ca2+](e), PTH secretion from bPT cells was inhibited with an IC50 of 1 mM, and ET-1 increased PTH release in a dose-dependent manner but without affecting the IC50 for the [Ca2+]e-dependent inhibition. Thus, the parathyroid epithelial cells appear to respond to ET-1 in a unique way, and the ET autocrine system can be regarded as a possible mechanism to modulate the sensitivity of [Ca2+]e-dependent PTH release. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,FLORENCE,ITALY. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RI Tomic, Melanija/C-3371-2016 NR 36 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1995 VL 10 IS 5 BP 716 EP 725 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU603 UT WOS:A1995QU60300007 PM 7639107 ER PT J AU LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL AF LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL TI PREVALENCE OF LOW FEMORAL BONE-DENSITY IN OLDER US WOMEN FROM NHANES-III SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID HIP FRACTURE; MINERAL DENSITY; RISK; OSTEOPOROSIS; PREDICTION; SITES; RACE AB Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to similar to 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20, or similar to 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD. The majority of these women are white, but the number of minority women with low BMD is not trivial. C1 CTR DIS CONTROL & PREVENT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. MAYO CLIN & MAYO FDN,DEPT DIAGNOST RADIOL,ROCHESTER,MN 55905. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NIA,BETHESDA,MD 20892. HELEN HAYES HOSP,REG BONE CTR,W HAVERSTRAW,NY. NIAMSD,BETHESDA,MD 20892. NR 39 TC 295 Z9 298 U1 2 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1995 VL 10 IS 5 BP 796 EP 802 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU603 UT WOS:A1995QU60300016 PM 7639115 ER PT J AU ZAMBRUNO, G MARCHISIO, PC MARCONI, A VASCHIERI, C MELCHIORI, A GIANNETTI, A DELUCA, M AF ZAMBRUNO, G MARCHISIO, PC MARCONI, A VASCHIERI, C MELCHIORI, A GIANNETTI, A DELUCA, M TI TRANSFORMING GROWTH-FACTOR-BETA-1 MODULATES BETA-1 AND BETA-5 INTEGRIN RECEPTORS AND INDUCES THE DE-NOVO EXPRESSION OF THE ALPHA-V-BETA-6 HETERODIMER IN NORMAL HUMAN KERATINOCYTES - IMPLICATIONS FOR WOUND-HEALING SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CULTURED HUMAN KERATINOCYTES; SQUAMOUS-CELL CARCINOMAS; EPITHELIAL-CELLS; TISSUE-REPAIR; DIFFERENTIAL EXPRESSION; FIBRONECTIN RECEPTOR; REGULATES EXPRESSION; BM-600 NICEIN; BURN WOUNDS AB The molecular mechanism underlying the promotion of wound healing by TGF-beta 1 is incompletely understood. We report that TGF-beta 1 regulates the regenerative/migratory phenotype of normal human keratinocytes by modulating their integrin receptor repertoire. In growing keratinocyte colonies but not in fully stratified cultured epidermis, TGF-beta 1: (a) strongly upregulates the expression of the fibronectin receptor alpha 5 beta 1, the vitronectin receptor alpha v beta 5, and the collagen receptor alpha 2 beta 1 by differentially modulating the synthesis of their alpha and beta subunits; (b) downregulates the multifunctional alpha 3 beta 1 heterodimer; (c) induces the de novo expression and surface exposure of the alpha v beta 6 fibronectin receptor; (d) stimulates keratinocyte migration toward fibronectin and vitronectin; (e) induces a marked perturbation of the general mechanism of polarized domain sorting of both beta 1 and beta 4 dimers; and (f) causes a pericellular redistribution of alpha v beta 5. These data suggest that alpha 5 beta 1, alpha v beta 6, and alpha v beta 5, not routinely used by keratinocytes resting on an intact basement membrane, act as ''emergency'' receptors, and uncover at least one of the molecular mechanisms responsible for the peculiar integrin expression in healing human wounds. Indeed, TGF-beta 1 reproduces the integrin expression pattern of keratinocytes located at the injury site, particularly of cells in the migrating epithelial tongue at the leading edge of the wound. Since these keratinocytes are inhibited in their proliferative capacity, these data might account for the apparent paradox of a TGF-beta 1-dependent stimulation of epidermal wound healing associated with a growth inhibitory effect on epithelial cells. C1 CTR BIOTECHNOL AVANZATE,EPITHELIAL BIOL & BIOTECHNOL UNIT,IST,NATL CANC INST,I-16132 GENOA,ITALY. IST SCI SAN RAFFAELE,DIBIT,DEPT BIOL & TECHNOL RES,I-20132 MILAN,ITALY. IST DERMOPATICO IMMACOLATA,ROME,ITALY. UNIV MODENA,DEPT DERMATOL,I-41100 MODENA,ITALY. RI Marconi, Alessandra/A-5389-2012; De Luca, Michele/N-5883-2014 OI Marconi, Alessandra/0000-0002-5667-5766; De Luca, Michele/0000-0002-0850-8445 FU Telethon [A.008] NR 94 TC 275 Z9 282 U1 0 U2 4 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 MAY PY 1995 VL 129 IS 3 BP 853 EP 865 DI 10.1083/jcb.129.3.853 PG 13 WC Cell Biology SC Cell Biology GA QW142 UT WOS:A1995QW14200025 PM 7537276 ER PT J AU WANG, HG MILLAN, JA COX, AD DER, CJ RAPP, UR BECK, T ZHA, HB REED, JC AF WANG, HG MILLAN, JA COX, AD DER, CJ RAPP, UR BECK, T ZHA, HB REED, JC TI R-RAS PROMOTES APOPTOSIS CAUSED BY GROWTH-FACTOR DEPRIVATION VIA A BCL-2 SUPPRESSIBLE MECHANISM SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN FOLLICULAR LYMPHOMA; HEMATOPOIETIC-CELL LINE; C-MYC; TRANSGENIC MICE; GENE-PRODUCT; B-CELLS; PROTEIN; DEATH; ONCOPROTEIN; EXPRESSION AB The Bcl-2 protein is an important regulator of programmed cell death, but the biochemical mechanism by which this protein prevents apoptosis remains enigmatic. Recently, Bcl-2 has been reported to physically interact with a member of the Ras superfamily of small GTPases, p23-R-Ras. To examine the functional significance of R-Ras for regulation of cell death pathways, the IL-3-dependent cells 32D.3 and FL5.12 were stable transfected with expression plasmids encoding an activated form (38 Glycine --> Valine) of R-Ras protein. R-Ras(38V)-producing 32D.3 and FL5.12 cells experienced increased rates of apoptotic cell death relative to control transfected cells when deprived of IL-3. Analysis of several independent clones of transfected 32D.3 cells revealed a correlation between higher levels of R-Ras protein and faster rates of cell death upon withdrawal of IL-3 from cultures. 32D.3 cells contransfected with R-Ras(38V) and Bcl-2 exhibited prolonged cell survival in the absence of IL-3, equivalent to 32D.3 cells transfected with Bcl-2 expression plasmids alone. R-Ras(38V) also increased rates of cell death in serum-deprived NIH-3T3 cells, and Bcl-2 again abrogated most of this effect. The ratio of GTP and GDP bound to R-Ras(38V) was not significantly different in control 32D.3 cells vs those that overexpressed Bcl-2, indicating that Bcl-2 does not abrogate R-Ras-mediated effects on cell death by altering R-Ras GDP/GTP regulation. Moreover, purified Bcl-2 protein had no effect on the GTPase activity of recombinant wild-type R-Ras in vitro. When expressed in Sf9 cells using recombinant baculoviruses, R-Ras(38V) bound to and induced activation of Raf-1 kinase irrespective of whether Bcl-2 does not nullify R-Ras effects by interfering with R-Ras-mediated activation of Raf-1 kinase. Taken together, these findings suggest that R-Ras enhances the activity of a cell death pathway in growth factor-deprived cells and imply that Bcl-2 acts downstream of R-Ras to promote cell survival. C1 LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. UNIV N CAROLINA,DEPT PHARMACOL,FLOB,CHAPEL HILL,NC 27599. NCI,FREDERICK RES FACIL,VIRAL ONCOL LAB,FREDERICK,MD 21702. RI Wang, Hong-Gang/A-3018-2015 NR 59 TC 108 Z9 109 U1 0 U2 0 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 MAY PY 1995 VL 129 IS 4 BP 1103 EP 1114 DI 10.1083/jcb.129.4.1103 PG 12 WC Cell Biology SC Cell Biology GA QY118 UT WOS:A1995QY11800019 PM 7744959 ER PT J AU SCHMIDT, KC MIES, G DIENEL, GA CRUZ, NF CRANE, AM SOKOLOFF, L AF SCHMIDT, KC MIES, G DIENEL, GA CRUZ, NF CRANE, AM SOKOLOFF, L TI ANALYSIS OF TIME COURSES OF METABOLIC PRECURSORS AND PRODUCTS IN HETEROGENEOUS RAT-BRAIN TISSUE - LIMITATIONS OF KINETIC MODELING FOR PREDICTIONS OF INTRACOMPARTMENTAL CONCENTRATIONS FROM TOTAL TISSUE ACTIVITY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE DEOXYGLUCOSE; KINETIC MODELING ID CEREBRAL GLUCOSE-UTILIZATION; DEOXYGLUCOSE METHOD; GRAPHICAL EVALUATION; TRANSFER CONSTANTS; LUMPED CONSTANT; PLASMA; LAMBDA AB The efficacy of various kinetic models to predict time courses of total radioactivity and levels of precursor and metabolic products was evaluated in heterogeneous samples of freeze-blown brain of rats administered [C-14]deoxyglucose ([C-14]DG). Two kinetic models designed for homogeneous tissues, i.e., a no-product-loss, three-rate-constant (3K) model and a first-order-product-loss, four-rate-constant (4K) model, and a third kinetic model designed for heterogeneous tissues without product loss [Tissue Heterogeneity (TH) Model] were examined. In the 45-min interval following a pulse of [C-14]DG, the fit of the TH Model to total tissue radioactivity was not statistically significantly better than that of the 3K Model, yet the TH Model described the time courses of [C-14]DG and its metabolites more accurately. The TH- and 4K-Model-predicted time courses of [C-14]DG and its metabolites were similar. Whole-brain glucose utilization (CMR(glc)) calculated with the TH or 3K Model, similar to 75 mu mol 100 g(-1) min(-1), was similar to values previously determined by model-independent techniques, whereas CMR(glc) calculated with the 4K Model was 44% higher. In a separate group of rats administered a programmed infusion to attain a constant arterial concentration of [C-14]DG that minimizes effects of tissue heterogeneity as well as any product loss, CMR(glc) calculated with all three models was 79 mu mol 100 g min(-1) at 45 min after initiation of the infusion. Statistical comparisons of goodness of fit of total tissue radioactivity were, therefore, not indicative of which models best describe the tissue precursor and product pools or which models provide the most accurate rates of glucose utilization. C1 MAX PLANCK INST NEUROL RES,DEPT EXPTL NEUROL,W-5000 COLOGNE,GERMANY. RP SCHMIDT, KC (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,RM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 8 Z9 8 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 MAY PY 1995 VL 15 IS 3 BP 474 EP 484 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QT257 UT WOS:A1995QT25700016 PM 7714006 ER PT J AU PINEDA, JD LEE, T AIN, K REYNOLDS, JC ROBBINS, J AF PINEDA, JD LEE, T AIN, K REYNOLDS, JC ROBBINS, J TI I-131 THERAPY FOR THYROID-CANCER PATIENTS WITH ELEVATED THYROGLOBULIN AND NEGATIVE DIAGNOSTIC SCAN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID WHOLE-BODY SCANS; SERUM THYROGLOBULIN; FOLLOW-UP; CARCINOMA; METASTASES; LUNG AB Seventeen patients with papillary thyroid cancer whose serum thyroglobulin (Tg) levels were elevated when hypothyroid, but whose diagnostic whole body scans were negative, were treated with 150-300 mCi I-131. Ah patients had total thyroidectomy and I-131 ablation for thyroid remnants. Before the study, 9 patients had I-131 therapy for tumor recurrence and/or metastases, and 5 patients had excisions of nonfunctioning metastasis. Radiological studies did not reveal evidence of metastases. In the initial evaluation, Tg levels ranged from 8-480 ng/mL (24 pmol/L to 1.5 nmol/L), and posttherapy whole body scans (RxWBS) revealed undiagnosed local recurrence and/or metastases in 16 of 17 patients. Follow-up from 6 months to 5 yr is available in 16 patients. RxWBS after a second treatment was positive in 8 of 13 patients, and after a third treatment in 5 of 5 patients, although in 3 cases, uptake in distant metastasis had disappeared. In 8 patients, Tg fell to 5 ng/mL or less. In 1 patient, RxWBS became negative, but Tg remained elevated; subsequent treatment revealed local and mediastinal uptake, but previous lung uptake had disappeared. In 8 patients, RxWBS remains positive, and elevated Tg persists. A total of 35 RxWBS were performed; 29 were positive. Follow-up Tg concentrations decreased in 81% of patients after the first treatment, in 90% after the second treatment, and in 100% of the patients after the third treatment. Tg (mean +/- se) decreased from 74 +/- 33 ng/mL in the first evaluation to 62 +/- 32 ng/mL in the second study and 32 +/- 20 ng/mL in the third study. The therapeutic effectiveness of I-131 treatment in patients with elevated Tg and negative diagnostic whole body scans is indicated by the conversion to negative RxWBS, the statistically significant decrease in the mean Tg level, and the reduction of serum Tg to 5 ng/mL or less in 50% of patients. Further experience with this therapeutic approach is required to evaluate its effectiveness in improving prognosis and survival. C1 NIDDKD, DEPT NUCL MED, GENET & BIOCHEM BRANCH, ENDOCRINOL SECT, BETHESDA, MD 20892 USA. NIH, DEPT NUCL MED, CTR CLIN, BETHESDA, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 22 TC 247 Z9 254 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1488 EP 1492 DI 10.1210/jc.80.5.1488 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100005 PM 7744991 ER PT J AU TAYLOR, SI AF TAYLOR, SI TI PRENATAL SCREENING FOR MUTATIONS IN THE INSULIN-RECEPTOR GENE - HOW RELIABLY DOES GENOTYPE PREDICT PHENOTYPE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID MUTANT ALLELES; RESISTANCE RP TAYLOR, SI (reprint author), NIDDKD, DIABET BRANCH, BLDG 10, ROOM 8S-239, 10 CTR DR, BETHESDA, MD 20892 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1493 EP 1495 DI 10.1210/jc.80.5.1493 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100006 PM 7538142 ER PT J AU SCHWARTZ, MW BOYKO, EJ KAHN, SE RAVUSSIN, E BOGARDUS, C AF SCHWARTZ, MW BOYKO, EJ KAHN, SE RAVUSSIN, E BOGARDUS, C TI REDUCED INSULIN-SECRETION - AN INDEPENDENT PREDICTOR OF BODY-WEIGHT GAIN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; OBESE ZUCKER RATS; FOOD-INTAKE; CEREBROSPINAL-FLUID; PIMA-INDIANS; RESISTANCE; BRAIN; TRANSPORT; PLASMA; DOGS AB A causal role in the pathogenesis of obesity has been proposed for hyperinsulinemia and insulin resistance in populations with a high prevalence of a ''thrifty genotype.'' An alternative hypothesis is that obesity-induced hyperinsulinemia is an adaptation which, by increasing central nervous system insulin signaling (which suppresses food intake), confers resistance to weight gain. To characterize the relationship between the level of insulin secretion and the risk of weight gain, we examined whether any of three different measures of the level of insulin secretion (the area under the plasma insulin curve during both a meal tolerance test and an oral glucose tolerance test, and the acute insulin secretory response to iv glucose) was predictive of weight gain in a prospective study of 97 Pima Indians (64 males and 33 females) with normal glucose tolerance. During a mean (+/- SD) follow-up period of more than 3 yr (males, 3.58 +/- 1.46 yr; females, 3.02 +/- 1.73 yr), average weight increased 2.1 +/- 3.0%/yr in males and 3.5 +/- 3.6%/yr in females, reflecting a mean annual increase in body fat content of 6.9%/yr in both sexes. Insulin secretion was negatively associated with the rate of weight gain, whether assessed by the insulin response during the meal tolerance test (r = -0.35; P < 0.001), the oral glucose tolerance test (r = -0.30; P = 0.004), or the acute insulin secretory response to iv glucose (r = -0.28; P = 0.002). Moreover, the significance of the relationship between each measure of insulin secretion and weight gain persisted after controlling for differences in age, sex, initial body weight, acid insulin sensitivity. Relatively reduced insulin secretion, therefore, is a significant and independent predictor of the tendency to gain weight and adiposity in Pima Indians. The presence of relative insulin resistance also conferred an independent reduction in the risk of weight gain in some regression analyses. We conclude that insulin resistance and hyperinsulinemia are unlikely to play a causal role in the development of obesity, and that relatively reduced insulin secretion is a marker of an increased risk of weight gain in this population. These conclusions support the hypothesis that the level of insulin secretion plays an important role in long term body weight regulation. C1 UNIV WASHINGTON, DEPT MED, SEATTLE, WA 98108 USA. NIDDKD, PHOENIX, AZ 85014 USA. RP SCHWARTZ, MW (reprint author), VET ADM MED CTR, 1660 S COLUMBIAN WAY, SEATTLE, WA 98108 USA. RI Schwartz, Michael/H-9950-2012; OI Kahn, Steven/0000-0001-7307-9002 NR 30 TC 107 Z9 109 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1571 EP 1576 DI 10.1210/jc.80.5.1571 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100022 PM 7745002 ER PT J AU HOERMANN, R POERTL, S LISS, I AMIR, SM MANN, K AF HOERMANN, R POERTL, S LISS, I AMIR, SM MANN, K TI VARIATION IN THE THYROTROPIC ACTIVITY OF HUMAN CHORIONIC-GONADOTROPIN IN CHINESE-HAMSTER OVARY CELLS ARISES FROM DIFFERENTIAL EXPRESSION OF THE HUMAN THYROTROPIN RECEPTOR AND MICROHETEROGENEITY OF THE HORMONE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN THYROID MEMBRANES; HUMAN TSH RECEPTORS; GLYCOPROTEIN HORMONES; TROPHOBLASTIC TUMORS; LUTEINIZING-HORMONE; INVITRO; HCG; STIMULATOR; GROWTH; RESPONSES AB The role of hCG as a stimulator of the human thyroid has been a subject of controversy, because discrepant results have been obtained in different in vitro assays. In an attempt to explain the variation observed in the thyroid response to hCG, we investigated the ability of hCG and that of its isoforms and glycosylation variants to inhibit [I-125]bovine (b) TSH binding and stimulate adenylate cyclase in two clones, JP09 and JP26, of Chinese hamster ovary cells stably transfected with the human TSH receptor (hTSHr). The two clones differed with respect to the number of hTSHr expressed per cell. (34,000 in JP09 and 2,000 in JP26 cells). Both responded extremely well. to bTSH; the cAMP response to 0.001 IU/L bTSH was distinguishable from basal values. Interestingly, JP09 cells were readily stimulated by hCG (20-100 mg/L; 0.52-2.6 x 10(-6) mol/L) to release cAMP, whereas JP26 cells showed little if any response. Also, cAMP stimulation produced by asialo-hCG was 12-fold in JP09 cells and only 4-fold in JP26 cells compared to 45- and 67-fold stimulations by bTSH, respectively. Stimulation by asialo-hCG was approximately 30% that of bTSH in JP09 cells, but less than 6% in JP26 cells. When assessing the thyrotropic activity of the microheterogeneous isoforms of hCG, more alkaline pi forms were found to be more active than those of a more acidic pi regardless of whether they were derived from normal or molar pregnancy urine. Further studies with hCG, asialo-hCG, asialoagalacto-hCG, and deglycosylated hCG revealed that removal of sialic acid caused a marked increase in both its affinity for hTSHr and its cAMP-releasing potency, whereas removal of further carbohydrate, although it slightly enhanced receptor binding, was detrimental to adenylate cyclase activation. In conclusion, differences in hTSHr expression may cause a variation in the cAMP response to hCG or its glycosylation variants, as does the microheterogeneity of the hormone itself. These mechanisms may be responsible at least in part for the divergent responses of different cell types to hCG and render interpretation of the physiological meaning of the data obtained in recombinant receptor systems difficult. C1 UNIV MUNICH, KLINIKUM GROSSHADERN, DEPT MED 2, D-81377 MUNICH, GERMANY. NATL INST HLTH, DIV RES GRANTS, BETHESDA, MD 20892 USA. RP UNIV ESSEN GESAMTHSCH, DEPT MED, DIV ENDOCRINOL, HUFELANDSTR 55, D-45122 ESSEN, GERMANY. OI Hoermann, Rudolf/0000-0002-1326-4270 NR 42 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1605 EP 1610 DI 10.1210/jc.80.5.1605 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100027 PM 7745007 ER PT J AU SCHIPANI, E WEINSTEIN, LS BERGWITZ, G IIDAKLEIN, A KONG, XF STUHRMANN, M KRUSE, K WHYTE, MP MURRAY, T SCHMIDTKE, J VANDOP, C BRICKMAN, AS CRAWFORD, JD POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV JUPPNER, H AF SCHIPANI, E WEINSTEIN, LS BERGWITZ, G IIDAKLEIN, A KONG, XF STUHRMANN, M KRUSE, K WHYTE, MP MURRAY, T SCHMIDTKE, J VANDOP, C BRICKMAN, AS CRAWFORD, JD POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV JUPPNER, H TI PSEUDOHYPOPARATHYROIDISM TYPE IB IS NOT CAUSED BY MUTATIONS IN THE CODING EXONS OF THE HUMAN PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR GENE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; NEPHROGENIC DIABETES-INSIPIDUS; VASOPRESSIN V2-RECEPTOR GENE; POLYMERASE CHAIN-REACTION; COMMON RECEPTOR; DNA FRAGMENTS; PROTEIN; RESISTANCE; CELLS; FIBROBLASTS AB Pseudohypoparathyroidism type Ib (PHP-Ib) is thought to be caused by a PTH/PTH-related peptide (PTHrP) receptor defect. To search for receptor mutations in genomic DNA from 17 PHP-Ib patients, three recently isolated human genomic DNA clones were further characterized by restriction enzyme mapping and nucleotide sequencing across intron/exon borders. Regions including all 14 coding exons and their splice junctions were amplified by polymerase chain reaction, and the products were analyzed by either temperature gradient gel electrophoresis or direct nucleotide sequencing. Silent polymorphisms were identified in exons G (1 of 17), M4 (1 of 17), and M7 (15 of 17). Two base changes were found in introns, 1 at the splice-donor site of the intron between exons E2 and E3 (1 of 17) and the other between exons G and M1 (2 of 17), Total ribonucleic acid from COS-7 cells expressing minigenes with or without the base change between exons E2 and E3 showed no difference by either Northern blot analysis or reverse transcriptase-polymerase chain reaction. Radioligand binding was indistinguishable for both transiently expressed constructs. A missense mutation (E546 to K546) in the receptor's cytoplasmic tail (3 of 17) was also found in 1 of 60 healthy individuals, and PTH/PTHrP receptors with this mutation were functionally indistinguishable from wild-type receptors. PHP-Ib thus appears to be rarely, if ever, caused by mutations in the coding exons of the PTH/PTHrP receptor gene. C1 MASSACHUSETTS GEN HOSP, MED & CHILDRENS SERV, PEDIAT ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED & CHILDRENS SERV, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NIDDK, METAB DIS BRANCH, BETHESDA, MD 20892 USA. HANNOVER MED SCH, HUMANGENET ABT, D-30114 HANNOVER, GERMANY. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV LUBECK, PADIAT KLIN, D-23538 LUBECK, GERMANY. VET ADM MED CTR, DEPT ENDOCRINOL, SEPULVEDA, CA 91343 USA. SHRINERS HOSP CRIPPLED CHILDREN, METAB RES UNIT, ST LOUIS, MO 63131 USA. WASHINGTON UNIV, JEWISH HOSP ST LOUIS, SCH MED, DIV BONE & MINERAL DIS, ST LOUIS, MO 63130 USA. ST MICHAELS HOSP, BONE MINERAL GRP, TORONTO, ON M5B 1A6, CANADA. OI Weinstein, Lee/0000-0002-1899-5152; Abou-Samra, Abdul/0000-0001-8735-1142 FU PHS HHS [R01-46718] NR 58 TC 88 Z9 89 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1611 EP 1621 DI 10.1210/jc.80.5.1611 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100028 PM 7745008 ER PT J AU MERICQ, V CASSORLA, F GARCIA, H AVILA, A BOWERS, CY MERRIAM, GR AF MERICQ, V CASSORLA, F GARCIA, H AVILA, A BOWERS, CY MERRIAM, GR TI GROWTH-HORMONE (GH) RESPONSES TO GH-RELEASING PEPTIDE AND TO GH-RELEASING HORMONE IN GH-DEFICIENT CHILDREN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SYNTHETIC HEXAPEPTIDE; NORMAL MEN; PITUITARY; SECRETION; INVITRO; ACTS; RAT AB The GH-releasing peptides (GHRPs) are a family of hexa- and heptapeptides that specifically stimulate GH secretion in normal adults and children. They would be an attractive potential form of therapy for GH deficiency (GHD) if they are also active in these patients. Their action, however, appears to result at least in part through hypothalamic responses, which may be impaired in GHD, and their ability to evoke a GH response in these patients must therefore be directly examined. We studied GH responses to the heptapeptide GHRP-1 in 22 prepubertal children with previously documented GHD and growth failure and compared them to responses to GHRH and the two peptides administered together. Patients received 1 mu g/kg GHRH-(1-44)NH2, 1 mu g/kg GHRP-1, or both, in random order. Tests were separated by at least 1 week. GHRP-1 evoked a significant GH response in 60% of the patients, comparable to the 68% who responded to GHRH. The magnitudes of the peak responses were similar (7.5 +/- 8.0 mu g/L to GHRP-1 and 11.2 +/- 12.1 to GHRH), although the duration of the GH rise was briefer after GHRP-1. Both responses were lower than those previously observed in normal subjects. There was a marked synergy in responses when the two were given together; the GH peak (34.2 +/- 44.8 mu g/L) significantly exceeded the sum of the individual responses, and the proportion of patients who responded (86%) was also higher. Thus, despite the absence of endogenous GHRH reflexes in most patients with GHD, these children can respond to GHRP-1 similarly to GHRH, and GHRP-1 can markedly enhance the response to GHRH. These results suggest that GHRPs or their analogs could form the basis for therapy of GHD. C1 UNIV CHILE, INST INVEST MATERNO INFANTIL, SANTIAGO, 20892, CHILE. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 70122 USA. TULANE UNIV, ENDOCRINOL & METAB SECT, NEW ORLEANS, LA 98195 USA. UNIV WASHINGTON, AMER LAKE VET AFFAIRS MED CTR, SEATTLE, WA 98195 USA. UNIV WASHINGTON, DIV METAB ENDOCRINOL & NUTR, SEATTLE, WA USA. RI Mericq, Veronica/F-3927-2010 NR 25 TC 29 Z9 29 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1681 EP 1684 DI 10.1210/jc.80.5.1681 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100038 PM 7745018 ER PT J AU BAIRD, DD UMBACH, DM LANSDELL, L HUGHES, CL SETCHELL, KDR WEINBERG, CR HANEY, AF WILCOX, AJ MCLACHLAN, JA AF BAIRD, DD UMBACH, DM LANSDELL, L HUGHES, CL SETCHELL, KDR WEINBERG, CR HANEY, AF WILCOX, AJ MCLACHLAN, JA TI DIETARY INTERVENTION STUDY TO ASSESS ESTROGENICITY OF DIETARY SOY AMONG POSTMENOPAUSAL WOMEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SEXUALLY DIMORPHIC NUCLEUS; BREAST-CANCER CELLS; PITUITARY-RESPONSIVENESS; NEONATAL EXPOSURE; FEMALE RATS; HORMONE; PHYTOESTROGENS; GENISTEIN; RECEPTORS; INVITRO AB We tested the hypothesis that postmenopausal women on a soy-supplemented diet show estrogenic responses. Ninety-seven postmenopausal women were randomized to either a group that was provided with soy foods for 4 weeks or a control group that was instructed to eat as usual. Changes in urinary isoflavone concentrations served as a measure of compliance and phytoestrogen dose. Changes in serum FSH, LH, sex hormone binding globulin, and vaginal cytology were measured to assess estrogenic response. The percentage of vaginal superficial cells (indicative of estrogenicity) increased for 19% of those eating the diet compared with 8% of controls (P = 0.06 when tested by ordinal logistic regression). FSH and LH did not decrease significantly with dietary supplementation as hypothesized, nor did sex hormone binding globulin increase. Little change occurred in endogenous estradiol concentration or body weight during the diet. Women with large increases in urinary isoflavone concentrations were not more likely to show estrogenic responses than were women with more modest increases. On the basis of published estimates of phytoestrogen potency, a 4-week, soy-supplemented diet was expected to have estrogenic effects on the liver and pituitary in postmenopausal women, but estrogenic effects were not seen. At most, there was a small estrogenic effect on vaginal cytology. C1 NIEHS, SURG RES ASSOCIATES, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DURHAM, NC USA. UNIV CINCINNATI, CHILDRENS HOSP, CINCINNATI, OH 45229 USA. RP BAIRD, DD (reprint author), NIEHS, EPIDEMIOL BRANCH, A3-05, POB 12233, RES TRIANGLE PK, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 38 TC 237 Z9 246 U1 1 U2 4 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 MAY PY 1995 VL 80 IS 5 BP 1685 EP 1690 DI 10.1210/jc.80.5.1685 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100039 PM 7745019 ER PT J AU ZELDIN, DC PLITMAN, JD KOBAYASHI, J MILLER, RF SNAPPER, JR FALCK, JR SZAREK, JL PHILPOT, RM CAPDEVILA, JH AF ZELDIN, DC PLITMAN, JD KOBAYASHI, J MILLER, RF SNAPPER, JR FALCK, JR SZAREK, JL PHILPOT, RM CAPDEVILA, JH TI THE RABBIT PULMONARY CYTOCHROME-P450 ARACHIDONIC-ACID METABOLIC PATHWAY - CHARACTERIZATION AND SIGNIFICANCE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EICOSANOID; EPOXYGENASE; EPOXYEICOSATRIENOIC ACID; DIHYDROXYEICOSATRIENOIC ACID; HYDROXYEICOSATETRAENOIC ACID ID LIVER MICROSOMAL CYTOCHROME-P-450; SPECIES-DEPENDENT EXPRESSION; CYTOSOLIC EPOXIDE HYDROLASE; EPOXYEICOSATRIENOIC ACIDS; SMOOTH-MUSCLE; RENAL-CORTEX; 12(R)-HYDROXYEICOSATRIENOIC ACID; 5,6-EPOXYEICOSATRIENOIC ACID; ENANTIOFACIAL SELECTIVITY; OXIDATIVE-METABOLISM AB Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney, Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome bg, metabolized arachidonic acid, producing primarily EETs, EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid, Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, ll(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid, At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung. C1 NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. VANDERBILT UNIV, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA. VANDERBILT UNIV, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA. UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75235 USA. MARSHALL UNIV, SCH MED, DEPT PHARMACOL, HUNTINGTON, WV 25755 USA. OI Falck, John/0000-0002-9219-7845 FU NHLBI NIH HHS [HL07123, HL27274]; NIGMS NIH HHS [GM37922] NR 77 TC 97 Z9 99 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2150 EP 2160 DI 10.1172/JCI117904 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500027 PM 7738183 ER PT J AU ALVAREZ, M PAULL, K MONKS, A HOSE, C LEE, JS WEINSTEIN, J GREVER, M BATES, S FOJO, T AF ALVAREZ, M PAULL, K MONKS, A HOSE, C LEE, JS WEINSTEIN, J GREVER, M BATES, S FOJO, T TI GENERATION OF A DRUG-RESISTANCE PROFILE BY QUANTITATION OF MDR-1/P-GLYCOPROTEIN IN THE CELL-LINES OF THE NATIONAL-CANCER-INSTITUTE ANTICANCER DRUG SCREEN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE P-GLYCOPROTEIN; DRUG RESISTANCE; MULTIDRUG RESISTANCE; POLYMERASE CHAIN REACTION; DRUG DEVELOPMENT ID P-GLYCOPROTEIN EXPRESSION; MDR1 GENE-EXPRESSION; MULTIDRUG-RESISTANCE; LEUKEMIA-CELLS; CYTOTOXICITY; REVERSAL; ACCUMULATION; SENSITIVITY; VINCRISTINE; TRANSPORTER AB Identifying new chemotherapeutic agents and characterizing mechanisms of resistance may improve cancer treatment. The Anticancer Drug Screen of the National Cancer Institute uses 60 cell lines to identify new agents. Expression of mdr-1/P-glycoprotein was measured by quantitative PCR. Expression was detected in 39 cell lines; the highest levels were in renal and colon carcinomas. Expression was also detected in all melanomas and central nervous system tumors, but in only one ovarian carcinoma and one leukemia cell line. Using a modified version of the COMPARE program, a high correlation was found between expression of mdr-l and cellular resistance to a large number of compounds. Evidence that these compounds are P-glycoprotein substrates includes: (a) enhancement of cytotoxicity by verapamil; (b) demonstration of cross-resistance in a multidrug-resistant cell line, (c) ability to antagonize P-glycoprotein, increasing vinblastine accumulation by decreasing efflux; and (d) inhibition of photoaffinity labeling by azidopine. Identification of many heretofore unrecognized compounds as substrates indicates that P-glycoprotein has a broader substrate specificity than previously recognized. This study confirms the validity of this novel approach and provides the basis for similar studies examining a diverse group of gene products, including other resistance mechanisms, putative drug targets, and genes involved in the cell cycle and apoptosis. C1 NCI, MED BRANCH, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 33 TC 174 Z9 177 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2205 EP 2214 DI 10.1172/JCI117910 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500033 PM 7738186 ER PT J AU GEHRT, A PETER, J PIZZO, PA WALSH, TJ AF GEHRT, A PETER, J PIZZO, PA WALSH, TJ TI EFFECT OF INCREASING INOCULUM SIZES OF PATHOGENIC FILAMENTOUS FUNGI ON MICS OF ANTIFUNGAL AGENTS BY BROTH MICRODILUTION METHOD SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INVITRO SUSCEPTIBILITY; MULTICENTER EVALUATION; MACRODILUTION; YEASTS AB Inoculum size is a critical variable in development of methods for antifungal susceptibility testing for filamentous fungi, In order to investigate the influence of different inoculum sizes on MICs of amphotericin B, 5-fluorocytosine, itraconazole, and miconazole, 32 clinical isolates (8 Aspergillus fumigatus, 8 Aspergillus flavus, 5 Rhizopus arrhizus, 8 Pseudallescheria boydii, and 3 Fusarium solani isolates) were studied by the broth microdilution method, Four inoculum sizes were studied: 1 x 10(2) to 5 x 10(2), 1 x 10(3) to 5 x 10(5), 1 x 10(4) to 5 x 10(4), and 1 x 10(5) to 5 x 10(5) CFU/ml. The National Committee for Clinical Laboratory Standards reference method for antifungal susceptibility testing in yeasts was modified and applied to filamentous fungi. The inoculum was spectrophotometrically adjusted, and all tests were performed in buffered medium (RPMI 1640) at pH 7.0 with incubation at 35 degrees C for 72 h. MICs were read at 24, 48, and 72 h. Amphotericin B showed a minimum effect of inoculum size on MICs for all species with the exception of P. boydii (P < 0.05), A significant effect of inoculum size on MICs was observed with 5-fluorocytosine, for which there was an increase of more than 10-fold in MICs against all Aspergillus spp, between inoculum concentrations of 10(2) and 10(4) CFU/ml (P < 0.001), For itraconazole, the results showed a more species-dependent increase of MICs, most strikingly for R. arrhizus and P. boydii, Miconazole, which,vas tested only with P. boydii, did not demonstrate a significant effect of inoculum size on MICs, In summary, the effect of inoculum size on MICs for filamentous fungi was dependent upon the organism and antifungal compound tested, Thus, among antifungal compounds, itraconazole and 5 fluorocytosine demonstrated significant inoculum effects, while amphotericin B and miconazole shelved comparatively minimum inoculum effects against pathogenic filamentous fungi, Moreover, among filamentous fungi, P. boydii and R. arrhizus exhibited the greatest inoculum effect. C1 NCI,INFECT DIS SECT,MYCOL UNIT,BETHESDA,MD 20892. NR 24 TC 64 Z9 67 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1995 VL 33 IS 5 BP 1302 EP 1307 PG 6 WC Microbiology SC Microbiology GA QT306 UT WOS:A1995QT30600049 PM 7615745 ER PT J AU BATTLES, JK WILLIAMSON, JC PIKE, KM GORELICK, PL WARD, JM GONDA, MA AF BATTLES, JK WILLIAMSON, JC PIKE, KM GORELICK, PL WARD, JM GONDA, MA TI DIAGNOSTIC ASSAY FOR HELICOBACTER-HEPATICUS BASED ON NUCLEOTIDE-SEQUENCE OF ITS 16S RIBOSOMAL-RNA GENE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID CAMPYLOBACTER-LIKE ORGANISMS; POLYMERASE CHAIN-REACTION; UNIDENTIFIED CURVED BACILLI; RIBOSOMAL-RNA; SP-NOV; REVERSE TRANSCRIPTION; EVOLUTIONARY DESCENT; HOMOSEXUAL MEN; PYLORI; GASTRITIS AB Conserved primers were used to PCR amplify 95% of the Helicobacter hepaticus 16S rRNA gene. Its sequence was determined and aligned to those of related bacteria, enabling the selection of primers to highly diverged regions of the 16S rRNA gene and an oligonucleotide probe for the development of a PCR-liquid hybridization assay. This assay was shown to be both sensitive and specific for H. hepaticus 16S rRNA gene sequences. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,LAB ANIM SCI PROGRAM,FREDERICK,MD 21702. RP BATTLES, JK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702, USA. NR 44 TC 43 Z9 43 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 MAY PY 1995 VL 33 IS 5 BP 1344 EP 1347 PG 4 WC Microbiology SC Microbiology GA QT306 UT WOS:A1995QT30600059 PM 7542270 ER PT J AU MARINCOLA, FM WHITE, DE WISE, AP ROSENBERG, SA AF MARINCOLA, FM WHITE, DE WISE, AP ROSENBERG, SA TI COMBINATION THERAPY WITH INTERFERON ALFA-2A AND INTERLEUKIN-2 FOR THE TREATMENT OF METASTATIC CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; DISSEMINATED MALIGNANT-MELANOMA; PURIFIED HUMAN INTERLEUKIN-2; PHASE-II TRIAL; RECOMBINANT INTERLEUKIN-2; ALPHA-INTERFERON; MURINE TUMORS; HALF-LIFE AB Purpose: Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFN alpha) and interleukin-2 (IL-2) in patients with metastatic cancer. Patients and Methods: From November 1987 through October 1990, 189 patients were treated with 379 courses. IFN alpha (3 x 10(6) U/m(2)) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m(2) (six patients, group 1), 7.8 x 10(6) IU/m(2) (32 patients, group 2), or 11.7 x 10(6) IU/m(2) (26 patients, group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m(2) plus IL-2 11.7 x 10(6) IU/m(2) (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10(6) IU/m(2) (29 patients, group 5) and 15.6 x 10(6) IU/m(2) (74 patients, group 6); however, because of IFN alpha-related toxicity, these two groups received IFN alpha once per day (6 x 10(6) U/m(2)). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval. Results: All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, fro groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFN alpha three times per day), no benefit for survival and increased toxicity were noted in this group. Conclusion: Based on these findings, we conclude that further studies of this combination treatment are not warranted. RP MARINCOLA, FM (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BLDG 10,ROOM 2B08,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 55 TC 78 Z9 78 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 MAY PY 1995 VL 13 IS 5 BP 1110 EP 1122 PG 13 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100010 PM 7738617 ER PT J AU SEIDMAN, AD REICHMAN, BS CROWN, JPA YAO, TJ CURRIE, V HAKES, TB HUDIS, CA GILEWSKI, TA BASELGA, J FORSYTHE, P LEPORE, J MARKS, L FAIN, K SOUHRADA, M ONETTO, N ARBUCK, S NORTON, L AF SEIDMAN, AD REICHMAN, BS CROWN, JPA YAO, TJ CURRIE, V HAKES, TB HUDIS, CA GILEWSKI, TA BASELGA, J FORSYTHE, P LEPORE, J MARKS, L FAIN, K SOUHRADA, M ONETTO, N ARBUCK, S NORTON, L TI PACLITAXEL AS 2ND AND SUBSEQUENT THERAPY FOR METASTATIC BREAST-CANCER - ACTIVITY INDEPENDENT OF PRIOR ANTHRACYCLINE RESPONSE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HAMSTER OVARY CELLS; MULTIDRUG RESISTANCE PHENOTYPE; PHASE-II; CROSS-RESISTANCE; J774.2 CELLS; CREMOPHOR EL; LUNG-CANCER; TAXOL; DRUG; MUTANTS AB Purpose: Two phase II clinical trials were performed to determine efficacy and tolerability of paclitaxel (Taxol; Bristol-Myers Squibb Co, Wallingford, CT) and granulocyte colony-stimulating factor ([G-CSF] Neupogen; Amgen, Inc, Thousand Oaks, CA) as second or subsequent therapy for metastotic breast cancer, Patients and Methods: paclitaxel plus G-CSF was administered as a second stage IV regimen to 25 patients with metastatic breast cancer at a dose of 250 mg/m(2) intravenously over 24 hours. Fifty-two patients received paclitaxel plus G-CSF at 200 mg/m(2) os a third or subsequent regimen (no restriction on number of prior regimens or on prior high-dose chemotherapy). All patients herd received prior anthracycline treatment, and ultimately had progressive bidimensionally measurable disease. Results: Twenty-five of 76 patients (32.8%) had a major objective response (95% confidence interval [CI], 14% to 37%). The median duration of response was 7 months (range, 1 to 20+), Responses were as likely in patients with disease demonstrated to be unresponsive to anthracycline, ie, de novo resistance (11 of 37, or 30%) as in those with disease that once exhibited anthracycline sensitivity, ie, acquired resistance, (10 of 31, or 32%). G-CSF administration was associated with febrile neutropenic episodes in 36 of 402 cycles (9%) in 16 of 76 patients (21%). Conclusion: Paclitaxel's clinically significant activity against metastatic breast cancer extends to patients with many prior chemotherapy regimens. The lock of impact of prior doxorubicin therapy on the likelihood of subsequent response to paclitaxel suggests an important role for this agent in the treatment of refractory metastatic breast cancer. (C) 1995 by American Society of Clinical Oncology. C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,WALLINGFORD,CT. NCI,MED BRANCH,BETHESDA,MD 20892. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,BREAST & GYNECOL CANC MED SERV,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-09207-14, 1-CM07311] NR 33 TC 213 Z9 214 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 MAY PY 1995 VL 13 IS 5 BP 1152 EP 1159 PG 8 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100015 PM 7537798 ER PT J AU KOHNE, CH HIDDEMANN, W SCHULLER, J WEISS, J LOHRMANN, HP SCHMITZHUBNER, U BODENSTEIN, H SCHOBER, C WILKE, H GREM, J SCHMOLL, HJ AF KOHNE, CH HIDDEMANN, W SCHULLER, J WEISS, J LOHRMANN, HP SCHMITZHUBNER, U BODENSTEIN, H SCHOBER, C WILKE, H GREM, J SCHMOLL, HJ TI FAILURE OF ORALLY-ADMINISTERED DIPYRIDAMOLE TO ENHANCE THE ANTINEOPLASTIC ACTIVITY OF FLUOROURACIL IN COMBINATION WITH LEUCOVORIN IN PATIENTS WITH ADVANCED COLORECTAL-CANCER - A PROSPECTIVE RANDOMIZED TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I TRIAL; FOLINIC ACID; BIOCHEMICAL MODULATION; CONTINUOUS INFUSION; CYTO-TOXICITY; 5-FLUOROURACIL; CARCINOMA; CELLS; AUGMENTATION; CHEMOTHERAPY AB Purpose: A randomized trial was performed to investigate the ability of the nucleoside transport inhibitor dipyridamole (DP) to enhance the antitumor activity of fluorouracil (5-FU)/leucovorin (folinic acid [FA]). Patients and Methods: One hundred eighty-one untreated patients with advanced colorectal cancer were randomized to receive 5-FU 600 mg/m(2) plus FA 300 mg/m(2) on days 2 to 4 with or without DP 75 mg orally three times daily on days 1 to 5. Cycles were repeated every 3 weeks. Only patients with documented tumor progression before therapy were eligible. 5-FU pharmacokinetics using high-performance liquid chromatography (HPLC) were assessed in 11 nonrandomized patients receiving paired cycles with or without DP. Results: One hundred seventy-four patients were assessable for toxicity and response. There was no significant difference in toxicity, except DP-related headache in 24% of patients. An objective response rate of 15% (one complete response [CR] and 13 partial responses [PRs]) for 5-FU/FA and 13% (two CRs and nine PRs) for 5-FU/FA/DP was observed. The dose-intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ significantly, except for a prolonged half-life (t(1/2)) induced by DP. The median time to progression (P = .8) and the median survival time (11.6 months for 5-FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different between treatment arms. Conclusion: Orally administered DP did not improve the antineoplastic activity of 5-FU/FA in patients with advanced colorectal cancer when used at this dose and schedule. The observed increase in 5-FU dose-intensity for FU/FA/DP was not clinically relevant. C1 HOSP RUDOLFSSTIFTUNG,VIENNA,AUSTRIA. UNIV GOTTINGEN,DEPT HEMATOL ONCOL,W-3400 GOTTINGEN,GERMANY. HOSP BARMHERZIGE,DEPT ONCOL,REGENSBURG,GERMANY. HOSP LEMGO,DEPT MED,LEMGO,GERMANY. HOSP HERFORD,DEPT MED,HERFORD,GERMANY. HOSP MINDEN,DEPT HEMATOL ONCOL,MINDEN,GERMANY. WESTDEUTSCH TUMORZENTRUM,ESSEN,GERMANY. USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. RP KOHNE, CH (reprint author), HANNOVER MED SCH,DEPT HEMATOL ONCOL,KONSTANTY GUTSCHOW STR 8,D-30625 HANNOVER,GERMANY. NR 35 TC 23 Z9 23 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 MAY PY 1995 VL 13 IS 5 BP 1201 EP 1208 PG 8 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100022 PM 7738622 ER PT J AU ADAMSON, PC BAILEY, J PLUDA, J POPLACK, DG BAUZA, S MURPHY, RF YARCHOAN, R BALIS, FM AF ADAMSON, PC BAILEY, J PLUDA, J POPLACK, DG BAUZA, S MURPHY, RF YARCHOAN, R BALIS, FM TI PHARMACOKINETICS OF ALL-TRANS-RETINOIC ACID ADMINISTERED ON AN INTERMITTENT SCHEDULE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; BINDING PROTEIN; RESISTANCE; VARIABILITY; PLASMA; CELLS AB Purpose: Administration of all-trans-retinoic acid (ATRA) on a continuous daily schedule results in a rapid and sustained decrease in plasma drug concentrations. This pharmacokinetic study was performed to determine if administration of ATRA on an intermittent schedule could overcome the rapid decrease in plasma drug concentration and provide repetitive periods of higher plasma drug exposure. Materials and Methods: ATRA was administered on repetitive cycles of 7 consecutive days of drug followed by 7 days without drug. On the days of pharmacokinetic monitoring, following an overnight fast, a fixed single oral dose of 40 mg/m(2) was administered and frequent plasma samples were obtained over 8 hours, Patients had pharmacokinetic studies performed on the first and seventh days of the first week, and on the first day of the third and eleventh weeks. ATRA was measured in plasma with a reverse-phase high-performance liquid chromatography (HPLC) assay. Results: Plasma exposure to ATRA as measured by the area under the plasma concentration-time curve (AUG) decreased significantly during the first week of drug administration, from a mean of 145 +/- 26 mu mol/L . min on day 1 to 18 +/- 4 mu mol/L . min by day 7. Plasma ATRA concentrations at the start of weeks 3 and 11 of this every-other-week schedule were equivalent to those achieved on day 1 of treatment, with mean AUCs of 177 +/- 39 and 128 +/- 30 mu mol/L . min, respectively. Conclusion: An intermittent schedule of ATRA administration results in repetitive periods of exposure to concentrations of ATRA normally only observed on the first day of treatment, phase II trials to evaluate the role of intermittent schedules of administration for ATRA are planned. C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 16 TC 55 Z9 56 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 MAY PY 1995 VL 13 IS 5 BP 1238 EP 1241 PG 4 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100027 PM 7738627 ER PT J AU PASCUAL, L HAYNES, OM GALPERIN, CZ BORNSTEIN, MH AF PASCUAL, L HAYNES, OM GALPERIN, CZ BORNSTEIN, MH TI PSYCHOSOCIAL DETERMINANTS OF WHETHER AND HOW MUCH NEW MOTHERS WORK - A STUDY IN THE UNITED-STATES AND ARGENTINA SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article ID LABOR-FORCE PARTICIPATION; MARRIED-WOMEN; FAMILY-LIFE; EMPLOYMENT; BIRTH; WIVES; PATTERNS; CHILDREN AB In this study, psychosocial predictors of mothers' decision to work and the number of hours worked (for working mothers) were examined in two contrasting cultural settings, the United States and Argentina. In total, 78 U.S. and 68 Argentine primiparous mothers of 5-month-old infants participated. In both settings, years of marriage and months that mothers worked during pregnancy predict whether mothers are employed after childbirth. By contrast, when the number of hours that mothers worked was predicted, different results were found in the two countries: Better educated women with higher status occupations work longer hours after childbirth in the United States, whereas better educated women with higher status occupations work fewer hours in Argentina. Different cultural and economic conditions in the two countries appear to mediate psychosocial determinants of women's decision to work. C1 NICHHD,BETHESDA,MD 20892. UNIV BUENOS AIRES,BUENOS AIRES,DF,ARGENTINA. UNIV BELGRANO,BUENOS AIRES,SANTA CRUZ,ARGENTINA. NR 51 TC 3 Z9 3 U1 1 U2 2 PU SAGE PUBL INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAY PY 1995 VL 26 IS 3 BP 314 EP 330 DI 10.1177/0022022195263006 PG 17 WC Psychology, Social SC Psychology GA QW639 UT WOS:A1995QW63900006 ER PT J AU BERNSTEIN, EF SMITH, PD THOMAS, GF XIE, HC MITCHELL, JB GLATSTEIN, E RUSSO, A AF BERNSTEIN, EF SMITH, PD THOMAS, GF XIE, HC MITCHELL, JB GLATSTEIN, E RUSSO, A TI A DIFFUSING SPHERE WHICH DELIVERS HOMOGENEOUS LASER-LIGHT FOR USE IN PHOTODYNAMIC THERAPY SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE PHOTODYNAMIC; LASER; TREATMENT; FIBEROPTIC; DIHEMATOPORPHYRIN; HEMATOPORPHYRIN ID BASAL-CELL CARCINOMA; PHOTORADIATION THERAPY; PHOTOFRIN-II; SKIN; TISSUE; TUMORS; MICE AB Photodynamic therapy (PDT) exploits the selective uptake of a photosensitizer in tumors and other hyperproliferative target tissues, as well as the ability to direct the treatment light beam to a specific region, Since the photodynamic effect depends upon light dose, tissue optical properties and photosensitizer concentration, uniform delivery of light is crucial to attain optimal photodynamic effect, Many commonly used methods for delivering laser light during photodynamic therapy, such as a free fiber or microlens, require fiber and laser adjustments to obtain a highly uniform beam. In this study we test the ability of a diffusing sphere to improve the uniformity of a light field coming from an argon laser coupled to a free fiber, in which no attempt has been made to optimize beam characteristics. Light fields from the free fiber, a microlens and the diffusing sphere are compared for uniformity via light intensity readings. An in vivo comparison between the sphere and the free fiber is also made in guinea pigs given Photofrin-II. The diffusing sphere decreases problems with shielding, allows quick and easy application of light by simply applying the device over the desired treatment area, and optimizes the desired photodynamic effect by producing a highly uniform beam of light with no necessity to optimize light delivery by vibrating, looping or re-cleaving fibers. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NIH,DIV BIOENGN,BETHESDA,MD 20892. UNIV TEXAS,SW MED SCH,DEPT RADIAT ONCOL,DALLAS,TX 75235. RP BERNSTEIN, EF (reprint author), THOMAS JEFFERSON UNIV,SCH MED,DEPT DERMATOL,BLUMLIE LIFE SCI BLDG,233 S 10TH ST,SUITE 450,PHILADELPHIA,PA 19107, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD MAY PY 1995 VL 9 IS 3 BP 195 EP 202 DI 10.1016/0923-1811(94)00377-Q PG 8 WC Dermatology SC Dermatology GA QX746 UT WOS:A1995QX74600006 PM 8664217 ER PT J AU GINSBURG, GT GOLLOP, R YU, YM LOUIS, JM SAXE, CL KIMMEL, AR AF GINSBURG, GT GOLLOP, R YU, YM LOUIS, JM SAXE, CL KIMMEL, AR TI THE REGULATION OF DICTYOSTELIUM DEVELOPMENT BY TRANSMEMBRANE SIGNALING SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE CAMP REGULATION; DIFFERENTIATION; PATTERN FORMATION; RECEPTORS ID CAMP RECEPTOR GENE; EXPRESSION; DISCOIDEUM; CAR1 AB Dictyostelium discoideum has a well characterized life cycle where unicellular growth and multicellular development are separated events. Development is dependent upon signal transduction mediated by cell surface, cAMP receptor/G protein linkages. Secreted cAMP acts extracellularly as a primary signal and chemoattractant. There are 4 genes for the distinct cAMP receptor subtypes, CAR1, CAR2, CAR3 and CAR4. These subtypes are expressed with temporally and spatially specific patterns and cells carrying null mutations for each gene have distinct developmental phenotypes. These results indicate an essential role for cAMP signalling throughout Dictyostelium development to regulate such diverse pathways as cell motility, aggregation (multicellularity), cytodifferentiation, pattern formation and cell type-specific gene expression. C1 NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DEPT ANAT & CELL BIOL,ATLANTA,GA 30322. NR 19 TC 24 Z9 25 U1 2 U2 2 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 1995 VL 42 IS 3 BP 200 EP 205 DI 10.1111/j.1550-7408.1995.tb01565.x PG 6 WC Microbiology SC Microbiology GA RD345 UT WOS:A1995RD34500002 PM 7496377 ER PT J AU BALDWIN, KM BOWERS, B AF BALDWIN, KM BOWERS, B TI ISOLATION OF N-ACETYL-BETA-HEXOSAMINIDASE FROM ACANTHAMOEBA-CASTELLANII SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE ANTIBODY CHARACTERIZATION; ANTIBODY PRODUCTION; LYSOSOMAL ENZYMES; MOLECULAR WEIGHT ID DICTYOSTELIUM-DISCOIDEUM; PROTEINS; ENZYME AB The lysosomal enzyme N-acetyl-beta-hexosaminidase (beta hex) has been purified from Acanthamoeba castellanii growth medium by a three step procedure. The enzyme was precipitated with ammonium sulfate, partially purified on a DE52 column and purified to homogeneity on an affinity column. The purified beta hex appeared to be a monomer with a molecular mass of 58 kDa and a pi of approximately 5.8. The enzyme activity in growth medium at RT was stable for several months. The purified beta hex was enzymatically deglycosylated and injected into two rabbits to make polyclonal antibodies. One antiserum was specific for beta hex, but the other stained many bands on immunoblots of whole cell preparations. Using fluorescently labelled secondary antibodies we have determined that both antisera stain digestive vacuoles in the Acanthamoeba cytoplasm, and do not stain the contractile vacuole. The multi-specific antiserum had high avidity for beta hex, but also stained the carbohydrate portion of other molecules. These other molecules may be lysosomal enzymes as well, since the activity of several other lysosomal enzymes was partially immunoprecipitable with the antiserum. We plan to use these antibodies to study traffic patterns among the variety of vacuolar structures in Acanthamoeba cytoplasm. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [1 F34 GM14609-01] NR 14 TC 2 Z9 2 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 1995 VL 42 IS 3 BP 237 EP 242 DI 10.1111/j.1550-7408.1995.tb01572.x PG 6 WC Microbiology SC Microbiology GA RD345 UT WOS:A1995RD34500009 PM 7496382 ER PT J AU DIAMOND, LS CLARK, CG CUNNICK, CC AF DIAMOND, LS CLARK, CG CUNNICK, CC TI YI-S, A CASEIN-FREE MEDIUM FOR AXENIC CULTIVATION OF ENTAMOEBA-HISTOLYTICA, RELATED ENTAMOEBA, GIARDIA-INTESTINALIS AND TRICHOMONAS-VAGINALIS SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE CASEIN DIGESTS; ENTAMOEBA INVADENS; ENTAMOEBA MOSHKOVSKII AB Pancreatic digests of casein are major ingredients of media used in the axenic cultivation of lumen-dwelling parasitic protozoa, especially Entamoeba, Giardia, and trichomonads. The digest used almost exclusively in the development of these media, Medo-Peptone (Trypticase(R) BBL), has not been available since 1981. Moreover, none of dozens of similar type digests tested since then in our laboratory has proved equal to Medo-Peptone, and in the last two years it has become increasingly difficult to obtain new batches which will support even modest growth of Entamoeba histolytica. In response to this problem we have developed a casein-free medium, YI-S, consisting of a nutrient broth, vitamin mixture and serum. We recommend it as a replacement for the casein-dependent medium TYI-S-33, currently the most widely used for axenic culture of Entamoeba histolytica and other lumen-dwellers. RP DIAMOND, LS (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 9 TC 74 Z9 76 U1 3 U2 5 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 1995 VL 42 IS 3 BP 277 EP 278 DI 10.1111/j.1550-7408.1995.tb01579.x PG 2 WC Microbiology SC Microbiology GA RD345 UT WOS:A1995RD34500016 PM 7496385 ER PT J AU YANG, YL MERCEP, M WARE, CF ASHWELL, JD AF YANG, YL MERCEP, M WARE, CF ASHWELL, JD TI FAS AND ACTIVATION-INDUCED FAS LIGAND MEDIATE APOPTOSIS OF T-CELL HYBRIDOMAS - INHIBITION OF FAS LIGAND EXPRESSION BY RETINOIC ACID AND GLUCOCORTICOIDS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; ANTIGEN RECEPTOR COMPLEX; MONOCLONAL-ANTIBODY; SURFACE ANTIGEN; MOLECULAR-CLONING; PERIPHERAL-BLOOD; CYCLOSPORINE-A; LPR/LPR MICE; CYCLE BLOCK; DEATH AB Activation of T cell hybridomas induces a G(1)/S cell cycle block and apoptosis. We isolated a variant of the 2B4.11 T cell hybridoma that, when activated via the TCR, produced IL-2 and underwent growth inhibition but did not die. Analysis of a variety of cell surface molecules revealed that the variant cell line, termed VD1, expressed very low levels of Fas compared to the wild type cells. Unlike 2B4.11 cells, VD1 cells were not killed by Fas ligand (FasL)-bearing effector cells. To determine if Fas is involved in activation-induced apoptosis, two different reagents that specifically bind Fas without killing the T cell hybridomas, a monoclonal antibody and a soluble Fas:Fc chimeric molecule, were added to activated T cell hybridomas. Both treatments prevented activation-induced apoptosis in a dose-dependent manner, but had no effect on IL-2 production or growth inhibition. Northern blot analysis revealed that unactivated 2B4.11 cells expressed negligible levels of FasL mRNA, but transcripts were detectable as early as 2 h after activation and continued to increase up to 4-6 h after activation. Anti-TCR induced activation of 2B4.11 cells in the presence of a TCR(-) 2B4.11 variant resulted in death of the unactivated ''bystander'' cells, which was inhibited by anti-Fas antibodies. Finally, treatment of T hybridoma cells with 9-cis retinoic acid or glucocorticoids, which are known to prevent activation-induced T cell apoptosis, inhibited the up-regulation of FasL. We conclude that up-regulated expression of FasL and its subsequent interaction with Fas accounts for the apoptotic response of T cell hybridomas to activation, and that retinoic acid and corticosteroids inhibit activation-induced apoptosis by preventing up-regulation of FasL. C1 NIH,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. FU NIAID NIH HHS [AI33068] NR 51 TC 193 Z9 199 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 MAY 1 PY 1995 VL 181 IS 5 BP 1673 EP 1682 DI 10.1084/jem.181.5.1673 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QV929 UT WOS:A1995QV92900009 PM 7536793 ER PT J AU NAKAJIMA, H GOLSTEIN, P HENKART, PA AF NAKAJIMA, H GOLSTEIN, P HENKART, PA TI THE TARGET-CELL NUCLEUS IS NOT REQUIRED FOR CELL-MEDIATED GRANZYME-BASED OR FAS-BASED CYTOTOXICITY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID MAMMALIAN-CELLS; APOPTOSIS; ATTACK AB The requirement for target cell nuclei in the two apoptotic death pathways used by cytotoxic lymphocytes was tested using model effector systems in which the granzyme and Fas pathways of target damage are isolated. Mast cell tumors expressing granzymes A and B in addition to cytolysin/perforin lysed tumor target cells about 10-fold more efficiently than comparable effector cells without granzymes. Enucleated cytoplast targets derived from these cells were also lysed with a similar 10-fold effect of granzymes. In contrast to cytoplasts, effector granzyme expression did not influence lysis of red cell targets. The Fas pathway was assessed using the selected cytotoxic T lymphocyte hybridoma subline d11S, which lysed target cells expressing Fas but not those lacking Fas. Similarly, cytoplasts derived from Fas(+) but not Fas(-) cells were also readily lysed by these effector cells. Thus, neither the nucleus itself nor the characteristic apoptotic nuclear damage associated with the two major cell death pathways used by cytotoxic lymphocytes are required for cell death per se. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. CNRS,INSERM,CTR IMMUNOL,F-13288 MARSEILLE 9,FRANCE. RI Golstein, Pierre/A-4954-2014 OI Golstein, Pierre/0000-0003-1750-3483 NR 30 TC 88 Z9 88 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 MAY 1 PY 1995 VL 181 IS 5 BP 1905 EP 1909 DI 10.1084/jem.181.5.1905 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QV929 UT WOS:A1995QV92900034 PM 7536799 ER PT J AU MULLER, M SCHNITZLER, P KOONIN, EV DARAI, G AF MULLER, M SCHNITZLER, P KOONIN, EV DARAI, G TI IDENTIFICATION AND PROPERTIES OF THE LARGEST SUBUNIT OF THE DNA-DEPENDENT RNA-POLYMERASE OF FISH LYMPHOCYSTIS DISEASE VIRUS - DRAMATIC DIFFERENCE IN THE DOMAIN ORGANIZATION IN THE FAMILY IRIDOVIRIDAE SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID MAJOR CAPSID PROTEIN; VACCINIA VIRUS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; GENE; GENOME; HOMOLOGY; EXPRESSION AB Cytoplasmic DNA viruses encode a DNA-dependent RNA polymerase (DdRP) that is essential for transcription of viral genes. The amino acid sequences of the known largest subunits of DdRPs from different species contain highly conserved regions. Oligonucleotide primers, deduced from two conserved domains (RQP[T/S]LH and NADFDGDE) were used for detecting the corresponding gene of fish lymphocystis disease virus (FLCDV), a member of the family Iridoviridae, which replicates in the cytoplasm of infected cells of flatfish. The gene coding for the largest subunit of the DdRP was identified using a PCR-derived probe. The screening of the complete EcoRI gene library of the viral genome led to the identification of the gene locus of the largest subunit of the DdRP within the EcoRI DNA fragment B (12.4 kbp, 0.034 to 0.165 map units). The nucleotide sequence of a part (8334 bp) of the EcoRI DNA fragment B was determined and a large ORF on the lower strand (ATG=5787; TAA=2190) was detected which encodes a protein of 1199 amino acids. Comparison of the amino acid sequences of the largest subunits of the DdRP (RPO1) of FLCDV and Chile iridescent virus (CIV) revealed a dramatic difference in their domain organization. Unlike the 1051 aa RPO1 of CIV, which lacks the C-terminal domain conserved in eukaryotic, eubacterial and other viral RNA polymerases, the 1199 aa RPO1 of FLCDV is fully collinear with its cellular and viral homologues. Despite this difference, comparative analysis of the amino acid sequences of viral and cellular RNA polymerases suggests a common origin for the largest RNA polymerase subunits of FLCDV and CIV. C1 UNIV HEIDELBERG, INST MED VIROL, D-69120 HEIDELBERG, GERMANY. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 42 TC 10 Z9 11 U1 1 U2 3 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 MAY PY 1995 VL 76 BP 1099 EP 1107 DI 10.1099/0022-1317-76-5-1099 PN 5 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA QW371 UT WOS:A1995QW37100004 PM 7730795 ER PT J AU HEINO, P SKYLDBERG, B LEHTINEN, M RANTALA, I HAGMAR, B KREIDER, JW KIRNBAUER, R DILLNER, J AF HEINO, P SKYLDBERG, B LEHTINEN, M RANTALA, I HAGMAR, B KREIDER, JW KIRNBAUER, R DILLNER, J TI HUMAN PAPILLOMAVIRUS TYPE-16 CAPSIDS EXPOSE MULTIPLE TYPE-RESTRICTED AND TYPE-COMMON ANTIGENIC EPITOPES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID OPEN READING FRAMES; VIRUS-LIKE PARTICLES; CONFORMATIONAL EPITOPES; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; INTACT VIRIONS; PROTEIN; BOVINE; L1; NEUTRALIZATION AB The study of viral infectivity and detection of viral capsid antigens of the major cervical cancer-associated human papillomavirus (HPV) type, HPV-16, requires knowledge of which epitopes are exposed in clinical specimens of infected tissue or on intact capsids. To define the antigenic epitopes of HPV-16, antisera to 66 overlapping synthetic peptides corresponding to the HPV-16 capsid proteins L1 and L2 and to seven peptide analogues were tested in immunoperoxidase stainings of consecutive sections from formalin-fixed, paraffin-embedded HPV infected tissue. Antisera against eleven different peptides from L1 and against seven different peptides from L2 recognized the HPV capsid antigen. Most epitopes were only found on the capsid antigen of certain genital HPV types, but four antigenic epitopes in L1 were detectable also in cutaneous wart specimens. All antigenic epitopes in L2 were restricted to genital HPV types and four L2 epitopes were only detectable in HPV-16 or HPV-33 positive specimens. The surface exposure of the antigenic epitopes was investigated by comparing the reactivity of the antipeptide antisera with intact or disrupted virions or capsids of HPV-11, HPV-16 and bovine papillomavirus (BPV). Twenty antipeptide sera from L1 and seven antipeptide sera from L2 were reactive with intact HPV-16 capsids at titres up to 1:146000. Sixteen of these antisera were also reactive with disrupted HPV-16 capsids. Cross-reactivity with disrupted HPV-11 and BPV was detected for eleven and six antisera, respectively, whereas intact HPV-11 or BPV virions showed only weak cross-reactivity. In conclusion, the HPV-16 L1 and L2 capsid proteins contained multiple antigenic epitopes, most of which were shared with one or several additional HPV types. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. SABBATSBERGS HOSP,DEPT CYTOL,S-11382 STOCKHOLM,SWEDEN. NATL PUBL HLTH INST,DEPT CHRON VIRAL DIS,HELSINKI,FINLAND. TAMPERE UNIV,CENT HOSP,DEPT PATHOL,SF-33520 TAMPERE,FINLAND. MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA. MILTON S HERSHEY MED CTR,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 34 TC 38 Z9 41 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 MAY PY 1995 VL 76 BP 1141 EP 1153 DI 10.1099/0022-1317-76-5-1141 PN 5 PG 13 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA QW371 UT WOS:A1995QW37100008 PM 7537325 ER PT J AU MARRONE, A DIBISCEGLIE, AM FOX, P AF MARRONE, A DIBISCEGLIE, AM FOX, P TI ABSENCE OF HEPATITIS-C VIRAL-INFECTION AMONG PATIENTS WITH PRIMARY SJOGRENS-SYNDROME SO JOURNAL OF HEPATOLOGY LA English DT Letter ID VIRUS-ANTIBODIES C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP MARRONE, A (reprint author), NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 6 TC 23 Z9 23 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0169-5185 J9 J HEPATOL JI J. Hepatol. PD MAY PY 1995 VL 22 IS 5 BP 599 EP 599 DI 10.1016/0168-8278(95)80461-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RL114 UT WOS:A1995RL11400018 PM 7650344 ER PT J AU ELSON, LH NUTMAN, TB METCALFE, DD PRUSSIN, C AF ELSON, LH NUTMAN, TB METCALFE, DD PRUSSIN, C TI FLOW CYTOMETRIC ANALYSIS FOR CYTOKINE PRODUCTION IDENTIFIES T-HELPER-1, T-HELPER-2, AND T-HELPER-0 CELLS WITHIN THE HUMAN CD4(+)CD27(-) LYMPHOCYTE SUBPOPULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; PROTECTIVE IMMUNITY; SOLUBLE FORM; SUBSETS; INTERLEUKIN-4; CD27; PROFILES; LEISHMANIASIS; STIMULATION; EXPRESSION AB Using three-color flow cytometric analysis for the detection of intracellular cytokines, we have been able to determine the exact combination of cytokines produced by individual T lymphocytes. Because CD4(+)CD27(-) lymphocytes have been shown to produce more IL-4 and IL-5 than CD4(+)CD27(+) lymphocytes, cells from normal individuals (n = 4) and helminth-infected patients (n = 4) were sorted magnetically for the CD4(+)CD27(+) and the CD4(+)CD27(-) subpopulations. Intracellular staining for IL-4, IL-5, and IFN-gamma subsequent to mitogen stimulation for 6 h revealed that although almost no CD4(+)CD27(-) lymphocytes produce both IL-5 and IFN-gamma (0.03-1.4%), a distinct proportion produce both IL-4 and IFN-gamma (0.1-8.0%), and 66% to 84% of IL-5-producing cells also produce IL-4. Patients and normal individuals had the same functional T cell subsets, but the CD4(+)CD27(-) lymphocytes from patients had higher frequencies of cells producing IL-4 (geometric mean (GM), 24.3% vs 16.4%) or IL-5 (CM, 10.2% vs 2.9%), whereas those of normal individuals had higher frequencies of cells producing IFN-gamma (GM, 44.5% vs 17.2%; p = 0.043). These analyses also revealed that the CD4(+)CD27(-) population included significantly higher frequencies of cells that were IL-5(+)IFN-gamma(-) (CM, 4.9% vs 1.5%; p = 0.025), IL-4(+)IFN-gamma(-) (GM, 13.8% vs 3.5%; p = 0.025), and IFN-gamma(+)IL-4(-)IL-5(-) (GM, 27.3% vs 12.0%; p = 0.011)than the CD4(+)CD27(+) population. Thus, we have clearly demonstrated Th1, Th2, and Th0 cell subsets within the CD4(+)CD27(-) population of human lymphocytes. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Prussin, Calman/0000-0002-3917-3326 NR 32 TC 151 Z9 153 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4294 EP 4301 PG 8 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500007 PM 7722288 ER PT J AU RESTIFO, NP BACIK, I IRVINE, KR YEWDELL, JW MCCABE, BJ ANDERSON, RW EISENLOHR, LC ROSENBERG, SA BENNINK, JR AF RESTIFO, NP BACIK, I IRVINE, KR YEWDELL, JW MCCABE, BJ ANDERSON, RW EISENLOHR, LC ROSENBERG, SA BENNINK, JR TI ANTIGEN-PROCESSING IN-VIVO AND THE ELICITATION OF PRIMARY CTL RESPONSES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC LYMPHOCYTES-T; CLASS-II REGION; ENDOGENOUSLY SYNTHESIZED PEPTIDE; RECOMBINANT VACCINIA VIRUSES; ENDOPLASMIC-RETICULUM; ADOPTIVE IMMUNOTHERAPY; DEFECTIVE PRESENTATION; POINT MUTATIONS; INFECTED-CELLS AB CD8(+) T lymphocytes (T-CD8+) play an important role in cellular immune responses. T-CD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which T-CD8+ induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of T-CD8+ responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the T-CD8+ immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,BETHESDA,MD 20814. RP RESTIFO, NP (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2842,10 CTR DR,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; yewdell, jyewdell@nih.gov/A-1702-2012; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 76 TC 180 Z9 182 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 MAY 1 PY 1995 VL 154 IS 9 BP 4414 EP 4422 PG 9 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500020 PM 7722298 ER PT J AU KURUCZ, I TITUS, JA JOST, CR JACOBUS, CM SEGAL, DM AF KURUCZ, I TITUS, JA JOST, CR JACOBUS, CM SEGAL, DM TI RETARGETING OF CTL BY AN EFFICIENTLY REFOLDED BISPECIFIC SINGLE-CHAIN FV DIMER PRODUCED IN BACTERIA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKEMIA-CELL-LINES; ANTI-TARGET CELL; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; CYTOTOXIC LYMPHOCYTES; ENDOPLASMIC-RETICULUM; HYBRID HYBRIDOMAS; T-CELLS; FRAGMENTS; PROTEIN AB A single-chain bispecific Fv dimer (bs(sFv)(2)) having specificity for mouse CD3 epsilon chain and human transferrin receptor was produced in bacterial inclusion bodies. To overcome difficulties associated with in vitro protein folding, we used a novel renaturation approach to obtain active bs(sFv)(2). The protein was dissolved in the weak ionic detergent sodium lauroylsarcosine, and disulfides were formed by oxidation in air. After oxidation, the bs(sFv)(2) exhibited very little covalent aggregation and migrated as a single species in nonreducing SDS-PACE, suggesting that disulfides were correctly paired. The detergent was removed using an ion exchange resin and the protein fractionated by size exclusion chromatography. The recovered 65-kDa protein was monomeric in nondenaturing solvent, homogeneous by SDS-PAGE, and comprised 15 to 20% of material applied to the gel filtration column. This protein bound specifically to both mouse CD3 epsilon chain and human transferrin receptor with affinities indistinguishable from those of the parental Fabs or single-chain Fvs. The bs(sFv)(2) specifically redirected mouse cytotoxic T cells to lyse target cells expressing human transferrin receptor at picomolar concentrations. Bacterially produced and detergent oxidized bs(sFv)(2) molecules may therefore provide the abundant amounts of homogeneous active material required to redirect cytotoxic cells against tumors and other unwanted cells in animal models and in patients. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NR 60 TC 46 Z9 48 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4576 EP 4582 PG 7 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500036 PM 7536774 ER PT J AU GROHMANN, U PUCCETTI, P BELLADONNA, ML FALLARINO, F BIANCHI, R BINAGLIA, L SAGAKUCHI, K MAGE, MG APPELLA, E FIORETTI, MC AF GROHMANN, U PUCCETTI, P BELLADONNA, ML FALLARINO, F BIANCHI, R BINAGLIA, L SAGAKUCHI, K MAGE, MG APPELLA, E FIORETTI, MC TI MULTIPLE POINT MUTATIONS IN AN ENDOGENOUS RETROVIRAL GENE CONFER HIGH IMMUNOGENICITY ON A DRUG-TREATED MURINE TUMOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-MEDIATED-IMMUNITY; LONG TERMINAL REPEAT; LYMPHOCYTES-T; EXPRESSION VECTOR; MASTOCYTOMA P815; LEUKEMIA-VIRUS; ANTIGEN; REJECTION; MICE; IDENTIFICATION AB Exposure in vivo of murine L5178Y lymphoma cells to cytoreductive triazene derivatives leads to the generation of immunogenic variant lines expressing new transplantation Ags recognized by CTL. In one such clonal variant (clone D), at least one subset of T cell neoepitopes are provided by proteins previously shown by serology to be products of endogenous retroviral env sequences. We report here on characterization of PCR-amplified gp70 env genes in clone D. Relative to known gp70 sequences in parental cells and in current databases, one gp70 sequence presented four distinct nucleotide changes, two of which were apparently unique to clone D DNA and cDNA upon differential hybridization analysis. Transfection experiments with the entire gp70 gene or subgenic fragments encompassing a single putative mutation showed that products of the mutated env gene or fragments may confer immunogenicity in vivo and susceptibility in vitro to lysis by clone D-primed, H-2K(d)- or H-2L(d)-restricted CTL. By skin test assay of mice primed with either clone D or three mutated synthetic peptides, evidence was obtained that amino acid substitutions at the relevant positions of the gp70 protein may produce immunogenic T cell epitopes and that these epitopes are expressed in vivo by clone D. These data point to the role of mutated retroviral tumor peptides as rejection Ags in histocompatible hosts. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP GROHMANN, U (reprint author), UNIV PERUGIA,DEPT EXPTL MED & BIOCHEM SCI,PHARMACOL SECT,VIA GIOCHETTO,I-06100 PERUGIA,ITALY. RI Fallarino, Francesca/O-3358-2013; OI Fallarino, Francesca/0000-0002-8501-2136; Puccetti, Paolo/0000-0001-6674-2128; Belladonna, Maria Laura/0000-0001-6522-0870; Grohmann, Ursula/0000-0001-7952-1850; Bianchi, Roberta/0000-0001-5914-4701 NR 41 TC 18 Z9 19 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 MAY 1 PY 1995 VL 154 IS 9 BP 4630 EP 4641 PG 12 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500042 PM 7722315 ER PT J AU IRVINE, KR MCCABE, BJ ROSENBERG, SA RESTIFO, NP AF IRVINE, KR MCCABE, BJ ROSENBERG, SA RESTIFO, NP TI SYNTHETIC OLIGONUCLEOTIDE EXPRESSED BY A RECOMBINANT VACCINIA VIRUS ELICITS THERAPEUTIC CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; ADOPTIVE IMMUNOTHERAPY; AUTOLOGOUS TUMOR; IMMUNE-RESPONSES; HUMAN-MELANOMA; CELL RECEPTOR; ANTIGEN; PEPTIDE; MUTANT; GENE AB P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene-induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse. A recombinant vaccinia virus (rVV) was constructed that expressed a synthetic oligonucleotide encoding the minimal determinant peptide of the tumor-associated Ag. Although the rVV recombinant expressing this mini-gene was recognized efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an endoplasmic reticulum insertion signal sequence to the NH2 terminus of the minimal determinant resulted in a rVV that elicited CD8(+) T cells that could lyse P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant viruses expressing synthetic oligonucleotide sequences preceded by the insertion signal sequences allow the expression of Ag directly into the endoplasmic reticulum, where binding to MHC class I molecules is most efficient. Vaccines based on synthetic oligonucleotides could be constructed with ease and rapidity but, most importantly, such constructs avoid the dangers associated with the expression of full length genes encoding TAA that are potentially oncogenic. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 39 TC 41 Z9 41 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 MAY 1 PY 1995 VL 154 IS 9 BP 4651 EP 4657 PG 7 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500044 PM 7722317 ER PT J AU WANG, M BRONTE, V CHEN, PW GRITZ, L PANICALI, D ROSENBERG, SA RESTIFO, NP AF WANG, M BRONTE, V CHEN, PW GRITZ, L PANICALI, D ROSENBERG, SA RESTIFO, NP TI ACTIVE IMMUNOTHERAPY OF CANCER WITH A NONREPLICATING RECOMBINANT FOWLPOX VIRUS ENCODING A MODEL TUMOR-ASSOCIATED ANTIGEN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-CELLS; VACCINIA VIRUS; BETA-GALACTOSIDASE; ENDOGENOUS ANTIGENS; MAMMALIAN-CELLS; IMMUNE-RESPONSE; GENE-TRANSFER; LACZ GENE; EXPRESSION; IDENTIFICATION AB Some tumor cells express Ags that are potentially recognizable by T lymphocytes and yet do not elicit significant immune responses. To explore new immunotherapeutic strategies aimed at enhancing the recognition of these tumor-associated Ags (TAA), we developed an experimental mouse model consisting of a lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was constructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recombinant FPV.bg40k, functioned effectively in vivo as an immunogen, eliciting CD8(+) T cells that could effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specific decreases in tumor burden and prolonged survival after treatment with the rFPV. These observations constitute the first reported use of rFPV in the prevention and treatment of an experimental cancer and suggest that changing the context in which the immune system encounters a TAA can significantly and therapeutically alter the host immune response against cancer. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NATL INST HLTH RES SCHOLARS PROGRAM,BETHESDA,MD 20814. THERION BIOL,CAMBRIDGE,MA 02142. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 50 TC 175 Z9 180 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4685 EP 4692 PG 8 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500048 PM 7722321 ER PT J AU WILLIAMS, ME CASPAR, P OSWALD, I SHARMA, HK PANKEWYCZ, O SHER, A JAMES, SL AF WILLIAMS, ME CASPAR, P OSWALD, I SHARMA, HK PANKEWYCZ, O SHER, A JAMES, SL TI VACCINATION ROUTES THAT FAIL TO ELICIT PROTECTIVE IMMUNITY AGAINST SCHISTOSOMA-MANSONI INDUCE THE PRODUCTION OF TGF-BETA, WHICH DOWN-REGULATES MACROPHAGE ANTIPARASITIC ACTIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; DELAYED-TYPE HYPERSENSITIVITY; CELL-MEDIATED-IMMUNITY; IFN-GAMMA; MONOCLONAL-ANTIBODY; ATTENUATED CERCARIAE; NONLIVING VACCINE; T-CELLS; RESPONSES; ACTIVATION AB C57BL/6 mice immunized intradermally (i.d.) with bacillus Calmette Guerin (BCG) plus killed skin-stage schistosomula are protected against subsequent infection with Schistosoma mansoni, whereas immunization by i.v. or i.m. routes is not protective. Moreover, previous immunization via the nonprotective i.v. route interfered with the ability to subsequently induce protection by i.d. vaccination, suggesting that inhibitory responses are invoked. Given the evidence that activated macrophages (M phi) play a role as effector cells in protection against schistosomiasis, we investigated the ability of spleen cells from protected and nonprotected immunized mice to produce M phi activating and deactivating cytokines. Exposure to supernatant fluids (SNs) from Ag stimulated spleen cells of i.d., but not i.v, or i.m., immunized mice activated inflammatory M phi for in vitro killing of schistosome larvae, through a mechanism dependent on both IFN gamma and TNF-alpha. No evidence was observed for the preferential induction of the M phi activating Th1 cytokines IFN-gamma and IL-2 in i.d. immunized mice, nor did spleen cells from nonprotected animals produce higher levels of the Th2 associated cytokines IL-4 and IL-10, which are known to prevent M phi activation. TCF-beta was, however, detected in SNs from unprotected mice. Moreover, the M phi inhibitory activity detected in these SNs was heat stable and neutralized by anti-TGF-beta Abs, suggesting that production of TCF-beta is at least partially responsible for the failure of i.m. and i.v. immunized mice to develop immunity to S. mansoni. Thus, the induction of down-regulatory cytokines may be an important factor limiting the efficacy of certain vaccination protocols. C1 NIAID,PARASITOL & TROP DIS BRANCH,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892. GENZYME CORP,BOSTON,MA 02139. UNIV VIRGINIA,SCH MED,DIV NEPHROL,CHARLOTTESVILLE,VA 22903. RI OSWALD, Isabelle/A-8497-2013 NR 43 TC 35 Z9 35 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 MAY 1 PY 1995 VL 154 IS 9 BP 4693 EP 4700 PG 8 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500049 PM 7722322 ER PT J AU WYNN, TA JANKOVIC, D HIENY, S CHEEVER, AW SHER, A AF WYNN, TA JANKOVIC, D HIENY, S CHEEVER, AW SHER, A TI IL-12 ENHANCES VACCINE-INDUCED IMMUNITY TO SCHISTOSOMA-MANSONI IN MICE AND DECREASES T-HELPER-2 CYTOKINE EXPRESSION, IGE PRODUCTION, AND TISSUE EOSINOPHILIA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; IRRADIATED CERCARIAE; PROTECTIVE IMMUNITY; RESPONSES; CELLS; INTERLEUKIN-12; INDUCTION; MOUSE; CD4+; IMMUNIZATION AB Vaccination of mice with radiation-attenuated cercariae of Schistosoma mansoni results in a highly significant but partial protection against challenge infection. This immunity is dependent on CD4(+) T cells, and because of its suppression by anti-IFN-gamma, appears to be caused by a Th1 response. Nevertheless, both Th1 and Th2 lymphokines are expressed in vaccinated and challenged mice, and we hypothesized that the expression of the latter group of down-regulatory cytokines may be responsible for the failure to obtain complete protection. Because IL-12 is a key cytokine that suppresses Th2-like responses, we asked whether IL-12 could increase vaccine-induced immunity to S. mansoni. Indeed, administration of IL-12 significantly reduced worm burdens following a challenge infection. IL-12-treated animals displayed a marked increase in pulmonary IFN-gamma and IL-12 p40 mRNA expression, while levels of IL-4, IL-5, and IL-13 were suppressed significantly during the period of vaccination. A marked decrease in serum IgE and tissue eosinophilia, two responses regulated by Th2 cytokines, was also observed. Surprisingly, IL-12-treated/vaccinated mice failed to demonstrate a significant increase in IFN-gamma, TNF-cr, or nitric oxide synthase mRNA at the time of challenge infection when compared with vaccinated controls, but did, however, display significantly suppressed Th2 cytokine mRNA production. Together, these data demonstrate that exogenous IL-12 regulates Th1/Th2 responses during immunization with irradiated cercariae, and suggest that this cytokine may be used to increase vaccine-induced immunity to S. mansoni. C1 NIAID,PARASIT DIS LAB,HOST PARASITE RELAT SECT,BETHESDA,MD 20892. RP WYNN, TA (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,9000 ROCKVILLE PIKE,BLDG 4-126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 50 TC 119 Z9 123 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4701 EP 4709 PG 9 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500050 PM 7722323 ER PT J AU CHAN, CC GERY, I KOHN, LD NUSSENBLATT, RB MOZES, E SINGER, DS AF CHAN, CC GERY, I KOHN, LD NUSSENBLATT, RB MOZES, E SINGER, DS TI PERIOCULAR INFLAMMATION IN MICE WITH EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS - A NEW EXPERIMENTAL BLEPHARITIS AND ITS MODULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEIBOMIAN GLAND DYSFUNCTION; T-CELLS; METHIMAZOLE THERAPY; GENE-EXPRESSION; DEFICIENT MICE; GRAVES-DISEASE; INDUCTION; PROTEIN; SHOCK AB Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal anti-DNA Ab, bearing a major Id 16/6Id. Immunized mice initially produce Abs to 16/6Id, DNA and nuclear Ags, and subsequently develop various clinical manifestations including leukopenia and renal immune complex disease. MHC class I Ags play a critical role in the induction and progression of experimental SLE. The present study reports that ocular changes also occur in mice with experimental SLE. The ocular disease is characterized by bilateral subacute and chronic inflammation of the eyelids (blepharitis) with immune complex IgG deposition and hypertrophic meibomian glands. The severity of ocular changes was strain dependent: most severe in 129 mice, less intense in BALB/c animals and only minimal in C3H.SW mice. No blepharitis developed in mice deficient in MHC class I expression. Further, the disease was strongly inhibited in BALB/c mice treated with methimazole, an agent that has been shown to repress transcription of MHC class I. In these cases, there was no IgG deposition and a decreased infiltration of inflammatory cells in the eyelids. These observations thus suggest that, similar to the observation with experimental SLE, MHC class I is critical in the onset of this experimental autoimmune blepharitis. The new experimental eye disease described here provides an animal model for chronic blepharitis in humans, a common condition for which such a model has been sought. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N103,10 CTR DR,MSC 1858,BETHESDA,MD 20892, USA. NR 31 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4830 EP 4835 PG 6 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500065 PM 7722331 ER PT J AU ENK, CD SREDNI, D BLAUVELT, A KATZ, SI AF ENK, CD SREDNI, D BLAUVELT, A KATZ, SI TI INDUCTION OF IL-10 GENE-EXPRESSION IN HUMAN KERATINOCYTES BY UVB EXPOSURE IN-VIVO AND IN-VITRO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NORMAL HUMAN-EPIDERMIS; NECROSIS-FACTOR-ALPHA; T-CELL CLONES; ULTRAVIOLET-RADIATION; INTERLEUKIN-1 ACTIVITY; CYTOKINE PRODUCTION; STIMULATORY FACTOR; LANGERHANS CELLS; MESSENGER-RNA; GROWTH AB Numerous studies have demonstrated that ultraviolet B (UVB) irradiation has profound effects on the skin and systemic immune systems. Because many of the effects of UVB result in suppression of contact sensitivity responses and because IL-10 induces a Th2 rather than a Th1 response, we sought to determine whether UVB irradiation induces IL-10 transcription and subsequent protein secretion by human epidermal cells. Skin of nine volunteers was exposed to UVB or sham irradiation, and epidermal cell suspensions were prepared from suction blister roofs 24 h thereafter. mRNA was extracted using oligo dT-coated magnetic beads, and IL-10 cDNA was amplified with a sensitive RT-PCR technique. We found that IL-10 was constitutively expressed by epidermal cells in 5 of 9 volunteers and that IL-10 message was up-regulated by UVB exposure in all experiments. Since epidermis consists of a heterogeneous cell population with distinct cytokine profiles, we determined whether UVB caused enhanced IL-10 transcription and protein secretion in human keratinocyte cultures. In these experiments, IL-10 was constitutively expressed by keratinocytes and UVB up-regulated IL-10 gene expression in a dose-dependent manner 24 h after in vitro irradiation, coinciding with IL-10 protein secretion into the culture supernatants. Taken together, the findings indicate that UVB irradiation induces IL-10 in human keratinocytes and suggest that keratinocyte-derived IL-10 may be an important component of the immunosuppression that results from UVB irradiation. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. BAR ILAN UNIV,DEPT INTERDISCIPLINARY,RAMAT GAN,ISRAEL. NR 55 TC 142 Z9 145 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1995 VL 154 IS 9 BP 4851 EP 4856 PG 6 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500068 PM 7722334 ER PT J AU JAKOBSEN, MK RESTIFO, NP COHEN, PA MARINCOLA, FM CHESHIRE, LB LINEHAN, WM ROSENBERG, SA ALEXANDER, RB AF JAKOBSEN, MK RESTIFO, NP COHEN, PA MARINCOLA, FM CHESHIRE, LB LINEHAN, WM ROSENBERG, SA ALEXANDER, RB TI DEFECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION IN A SARCOMATOID RENAL-CELL CARCINOMA CELL-LINE SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE MHC CLASS I; RENAL CELL CARCINOMA; BETA(2)-MICROGLOBULIN ID HLA CLASS-I; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN-MELANOMA; ANTIGEN PRESENTATION; GENE; HEAVY; CANCER AB We studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of beta(2)-microglobulin (beta(2)m) and MHC class I by now cytometry. Immunofluorescence staining using three different monoclonal antibodies to beta(2)m revealed no detectable beta(2)m in the endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of beta(2)m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for beta(2)m resulted in normal expression of both beta(2)m and class I (HLA-A, B, C) determinants assessed by now cytometry analysis. No expression of class I or beta(2)m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of beta(2)m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cytotoxic T cells and provides a mechanism for escape from immune recognition by the tumor. C1 NATL CANC INST,SURG BRANCH,BETHESDA,MD. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 30 TC 15 Z9 15 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 MAY PY 1995 VL 17 IS 4 BP 222 EP 228 DI 10.1097/00002371-199505000-00004 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA RN346 UT WOS:A1995RN34600004 PM 7582258 ER PT J AU PARKINSON, DR AF PARKINSON, DR TI UNTITLED SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material RP PARKINSON, DR (reprint author), NATL CANC INST,INVEST DRUG BRANCH,EXECUT PLAZA N,7TH FLOOR,ROOM 715 6130 EXECUT BLV,ROCKVILLE,MD 20852, USA. 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 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1995 VL 17 IS 4 BP A4 EP A4 DI 10.1097/00002371-199505000-00001 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA RN346 UT WOS:A1995RN34600001 ER PT J AU KARRON, RA WRIGHT, PF HALL, SL MAKHENE, M THOMPSON, J BURNS, BA TOLLEFSON, S STEINHOFF, MC WILSON, MH HARRIS, DO CLEMENTS, ML MURPHY, BR AF KARRON, RA WRIGHT, PF HALL, SL MAKHENE, M THOMPSON, J BURNS, BA TOLLEFSON, S STEINHOFF, MC WILSON, MH HARRIS, DO CLEMENTS, ML MURPHY, BR TI A LIVE ATTENUATED BOVINE PARAINFLUENZA VIRUS TYPE-3 VACCINE IS SAFE, INFECTIOUS, IMMUNOGENIC, AND PHENOTYPICALLY STABLE IN INFANTS AND CHILDREN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TEMPERATURE-SENSITIVE PHENOTYPE; PARA-INFLUENZA; REASSORTANT VIRUS; HEMAGGLUTININ-NEURAMINIDASE; NUCLEOTIDE-SEQUENCE; ADULT VOLUNTEERS; SUBUNIT VACCINE; AVIAN-HUMAN; REINFECTION; DISEASE AB The safety, infectivity, immunogenicity, transmissibility, and phenotypic stability of an intranasal bovine parainfluenza virus type 3 (BPIV-3) candidate vaccine was evaluated in a randomized, double-blind, placebo-controlled trial. Of human parainfluenza virus type 3 (HPIV-3)-seronegative children, 92% were infected, and 92% developed a serum hemagglutination-inhibiting (HAI) antibody response to BPIV-3 and 61% to HPIV-3. Geometric mean HAI titers were 1:40 to BPIV-3 and 1:16 to HPIV-3. In studies to evaluate vaccine transmissibility, none of 14 placebo recipients in close contact with 14 vaccinees shed BPIV-3. BPIV-3 isolates from seronegative vaccinees retained the attenuation phenotype when tested in rhesus monkeys. Although it is difficult to evaluate the safety and immunogenicity of such a vaccine in an open population of children who frequently become infected with HPIV-3, it appears that the live BPIV-3 vaccine is attenuated, infectious, immunogenic, poorly transmissible, and phenotypically stable and warrants further evaluation as a candidate vaccine in infants and children. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,VACCINE EVALUAT UNIT,NASHVILLE,TN 37212. RP KARRON, RA (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,DEPT INT HLTH,624 N BROADWAY,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-05050, AI-15095] NR 35 TC 94 Z9 95 U1 0 U2 2 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 MAY PY 1995 VL 171 IS 5 BP 1107 EP 1114 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000005 PM 7751684 ER PT J AU KOJIMA, E SHIRASAKA, T ANDERSON, BD CHOKEKIJCHAI, S STEINBERG, SM BRODER, S YARCHOAN, R MITSUYA, H AF KOJIMA, E SHIRASAKA, T ANDERSON, BD CHOKEKIJCHAI, S STEINBERG, SM BRODER, S YARCHOAN, R MITSUYA, H TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) VIREMIA CHANGES AND DEVELOPMENT OF DRUG-RELATED MUTATIONS IN PATIENTS WITH SYMPTOMATIC HIV-1 INFECTION RECEIVING ALTERNATING OR SIMULTANEOUS ZIDOVUDINE AND DIDANOSINE THERAPY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; AZT; DIDEOXYCYTIDINE; AZIDOTHYMIDINE; DIDEOXYINOSINE; AMPLIFICATION AB The changes in viremia levels and the development of drug-related mutations were examined in 26 patients with symptomatic human immunodeficiency virus type 1 (HIV-1) infection participating in a randomized trial comparing alternating (A) and simultaneous (S) regimens of zidovudine and didanosine therapy, Patients on both arms had significant reduction in serum RNA copies from baseline throughout the 2 years of study, Significant differences between the two arms were demonstrated over the first 2-3 months of therapy, Analyses with nested polymerase chain reaction revealed that the emergence of the didanosine-related position 74 Leu-->Val mutation was significantly blocked in both regimens, while the zidovudine-related mutation at codon 215 was not affected. Determination of the overall durability of the antiviremic effect of the A and S regimens of zidovudine and didanosine and clinical implications of the results require further research. C1 NCI,METAB BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,METAB BRANCH,RETROVIRUS DIS SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. NR 33 TC 39 Z9 39 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 MAY PY 1995 VL 171 IS 5 BP 1152 EP 1158 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000011 PM 7751690 ER PT J AU JAPOUR, AJ WELLES, S DAQUILA, RT JOHNSON, VA RICHMAN, DD COOMBS, RW REICHELDERFER, PS KAHN, JO CRUMPACKER, CS KURITZKES, DR AF JAPOUR, AJ WELLES, S DAQUILA, RT JOHNSON, VA RICHMAN, DD COOMBS, RW REICHELDERFER, PS KAHN, JO CRUMPACKER, CS KURITZKES, DR TI PREVALENCE AND CLINICAL-SIGNIFICANCE OF ZIDOVUDINE RESISTANCE MUTATIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATED FROM PATIENTS AFTER LONG-TERM ZIDOVUDINE TREATMENT SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE; THERAPY; SENSITIVITY; DIDANOSINE; HIV; AZT AB Zidovudine resistance mutations at reverse transcriptase codons 215 or 41 were found in two-thirds of human immunodeficiency virus type 1 (HIV-1) isolates obtained at baseline from patients enrolled in an AIDS Clinical Trials Group (ACTG) protocol that compared didanosine with continued zidovudine in patients with greater than or equal to 16 weeks of previous zidovudine therapy (ACTG 116B/117). The combined presence of mutations at both codons 215 and 41 conferred an increased risk for progression (relative hazard, 1.82; 95% confidence interval [CI], 1.02-3.26) and an increased risk for death (RH, 5.42; 95% CI, 1.92-15.30) in analyses that controlled for other factors predictive of progression. However, the benefit of switching to didanosine compared with continued zidovudine therapy was independent of the presence of these mutations. Although this information is not helpful in determining when to alter therapy, detection of zidovudine resistance mutations provides prognostic information in patients with advanced HIV disease. C1 UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80206. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,CTR STAT DATA ANAL,BOSTON,MA 02115. UNIV ALABAMA,BIRMINGHAM,AL. VET ADM MED CTR,BIRMINGHAM,AL. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV WASHINGTON,SEATTLE,WA 98195. NIAID,DIV AIDS,MED BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. FU NIAID NIH HHS [AI-27659, AI-29193, AI-32794] NR 24 TC 122 Z9 123 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 MAY PY 1995 VL 171 IS 5 BP 1172 EP 1179 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000014 PM 7538548 ER PT J AU NGUYEN, BY YARCHOAN, R WYVILL, KM VENZON, DJ PLUDA, JM MITSUYA, H BRODER, S AF NGUYEN, BY YARCHOAN, R WYVILL, KM VENZON, DJ PLUDA, JM MITSUYA, H BRODER, S TI 5-YEAR FOLLOW-UP OF A PHASE-I STUDY OF DIDANOSINE IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AIDS-RELATED COMPLEX; RECEIVING ANTIRETROVIRAL THERAPY; 2',3'-DIDEOXYINOSINE DDI; COMBINATION THERAPY; NATURAL-HISTORY; HIV-INFECTION; ZIDOVUDINE; SURVIVAL; TOXICITY; TRIAL AB Starting in 1988, 72 patients with advanced human immunodeficiency virus (HIV) infection were enrolled in a phase I study of didanosine at the National Cancer Institute, Beginning in 1992, patients with decreases in CD4 cell counts could switch to a combination of zidovudine and didanosine, The estimated median survival for all patients was 28 months (95% confidence interval, 23-46), However, for patients whose entry CD4 cell counts were 100-300/mm(3) the estimated 4-year survival was 80%. Baseline CD4 and CD8 cell counts, hemoglobin, lymphocytes, sedimentation rates, diagnosis of AIDS, and fever were significant predictors of overall survival, Principal toxicities were pancreatitis and peripheral neuropathy; no new toxicities were seen with extended didanosine treatment that had not been observed in shorter-term studies, This 5-year follow-up shows that didanosine can be tolerated for >4 years in some patients with advanced HIV infection and may have particular long-term utility in patients with moderately advanced immunosuppression. C1 NCI,MED BRANCH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 50 TC 15 Z9 15 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 MAY PY 1995 VL 171 IS 5 BP 1180 EP 1189 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000015 PM 7751692 ER PT J AU HUGHES, WT LAFON, SW SCOTT, JD MASUR, H AF HUGHES, WT LAFON, SW SCOTT, JD MASUR, H TI ADVERSE EVENTS ASSOCIATED WITH TRIMETHOPRIM-SULFAMETHOXAZOLE AND ATOVAQUONE DURING THE TREATMENT OF AIDS-RELATED PNEUMOCYSTIS-CARINII PNEUMONIA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PENTAMIDINE; TRIAL; 566C80 AB Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration. C1 BURROUGHS WELLCOME CO, DEPT INFECT DIS, RES TRIANGLE PK, NC USA. BURROUGHS WELLCOME CO, DEPT IMMUNOL & CLIN STAT, RES TRIANGLE PK, NC USA. NIH, DEPT CRIT CARE MED, BETHESDA, MD USA. NIAID, AIDS CLIN TRIAL GRP, BETHESDA, MD USA. RP ST JUDE CHILDRENS RES HOSP, DEPT INFECT DIS, 332 N LAUDERDALE, MEMPHIS, TN 38101 USA. NR 9 TC 46 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1995 VL 171 IS 5 BP 1295 EP 1301 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000031 PM 7751706 ER PT J AU ROH, JY STANLEY, JR AF ROH, JY STANLEY, JR TI PLAKOGLOBIN BINDING BY HUMAN DSG3 (PEMPHIGUS-VULGARIS ANTIGEN) IN KERATINOCYTES REQUIRES THE CADHERIN-LIKE INTRACYTOPLASMIC SEGMENT SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CELL-ADHESION MOLECULES; CONSTITUTIVE TRANSMEMBRANE GLYCOPROTEIN; NON-EPIDERMAL DESMOSOMES; AMINO-ACID-SEQUENCE; BETA-CATENIN; MR-165000 DESMOGLEIN; N-CADHERIN; FAMILY; IDENTIFICATION; JUNCTIONS AB Desmogleins are transmembrane desmosomal cadherins, Two desmogleins, Dsg3 and Dsg1, have been shown to bind plakoglobin, an intracytoplasmic (IC) desmosomal plaque protein, This binding may be critical for desmosome assembly or stability, The IC domain of desmogleins consists of subdomains that are either desmoglein specific or homologous with the IC region of classical cadherins, Here we identify the domains of human Dsg3 that are critical for plakoglobin binding in human keratinocytes. We constructed eukaryotic expression vectors containing chimeric cDNAs that encode the extracellular domain of mouse E-cadherin (Ecad) with the transmembrane and IC domains of Dsg3, with increasing truncations eliminating various IC subdomains from the carboxy-terminus. These constructs were used for transient transfection of HaCaT cells. Extracts were subjected to immunoprecipition with an anti-mouse Ecad antibody (that does not precipitate human Ecad), thus precipitating the chimeric protein and any tightly associated plakoglobin. Go-precipitation of plakoglobin was confirmed by immunoblotting. These data show that the desmoglein-specific IC subdomains are not necessary for plakoglobin binding, but the carboxy-terminal 87 amino acids of the IC-cadherin-like segment subdomain are critical, Finally, we confirmed these results outside cells with in vitro transcription and translation, which also demonstrates that the Dsg3-plakoglobin interaction is direct and does not depend on other cellular factors, These results underscore the importance of a region, highly conserved in all desmogleins, in the carboxy terminus of the IC-cadherin-like subdomain for the localization of plakoglobin to desmosomes. C1 UNIV PENN,DEPT DERMATOL,PHILADELPHIA,PA 19104. NIH,DERMATOL BRANCH,BETHESDA,MD 20892. NR 36 TC 34 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1995 VL 104 IS 5 BP 720 EP 724 DI 10.1111/1523-1747.ep12606963 PG 5 WC Dermatology SC Dermatology GA QX926 UT WOS:A1995QX92600003 PM 7738346 ER PT J AU HERTL, M NECKERS, LM KATZ, SI AF HERTL, M NECKERS, LM KATZ, SI TI INHIBITION OF INTERFERON-GAMMA-INDUCED INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION ON HUMAN KERATINOCYTES BY PHOSPHOROTHIOATE ANTISENSE OLIGODEOXYNUCLEOTIDES IS THE CONSEQUENCE OF ANTISENSE-SPECIFIC AND ANTISENSE-NON-SPECIFIC EFFECTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID OLIGONUCLEOTIDES; CELLS; INVITRO; DNA AB Expression of intercellular adhesion molecule-1 (ICAM-1) by keratinocytes is an important event in the pathogenesis of T-cell-mediated inflammatory skin diseases. To determine if ICAM-1 expression could be selectively modulated, two antisense phosphorothioate oligonucleotides (S-ODN) targeting the translation initiation and 3' untranslated regions of ICAM-1 mRNA were added as lipid complexes to cultures of keratinocytes. Interferon-gamma was added after 24 h to induce ICAM-1 expression, which was quantitated by flow cytometry after 48 h. The S-ODN targeting the translation initiation site did not inhibit ICAM-1 expression at 0.2-20.0 mu M. In contrast, 0.2-1.0 mu M of the S-ODN targeting a site in the 3' untranslated region abrogated ICAM-1 expression in up to 75% of the keratinocytes; this inhibition was reversible when complementary sense S-ODN was added. Phosphodiester ODN (PD-ODN) targeting the same sites did not inhibit ICAM-1 expression on keratinocytes, most likely as a consequence of rapid degradation. Inhibition of ICAM-1 by the antisense S-ODN was selective; expression of beta 2-microglobulin, alpha 3-integrin, and beta 1-integrin remained largely unaffected and interferon-gamma-induced HLA-DR expression was inhibited to a much lesser extent than ICAM-1. Antisense-non-specific inhibition was also noted in that two scrambled S-ODN with an identical nucleotide (14 of 20 cytosines) composition inhibited ICAM-1 expression in up to 44% of the keratinocytes, whereas a degenerate S-ODN did not. The data demonstrate the complex effects exerted by antisense S-ODN in that ICAM-1 expression was inhibited via antisense-non-specific mechanisms probably due to the intrinsic properties of the S-ODN as well as via the anticipated sequence-specific mechanisms. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 20 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1995 VL 104 IS 5 BP 813 EP 818 DI 10.1111/1523-1747.ep12607006 PG 6 WC Dermatology SC Dermatology GA QX926 UT WOS:A1995QX92600021 PM 7738361 ER PT J AU BOGARDUS, C AF BOGARDUS, C TI AGONIST - THE CASE FOR INSULIN-RESISTANCE AS A NECESSARY AND SUFFICIENT CAUSE OF TYPE-II DIABETES-MELLITUS SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material ID PIMA-INDIANS; GLUCOSE; DYSFUNCTION; POPULATION; SECRETION C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 16 TC 4 Z9 4 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 MAY PY 1995 VL 125 IS 5 BP 556 EP 558 PG 3 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA QW171 UT WOS:A1995QW17100003 PM 7738420 ER PT J AU BOGARDUS, C AF BOGARDUS, C TI REBUTTAL TO ANTAGONIST SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material RP BOGARDUS, C (reprint author), NIDDKD,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 0 TC 0 Z9 0 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 MAY PY 1995 VL 125 IS 5 BP 565 EP 565 PG 1 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA QW171 UT WOS:A1995QW17100006 ER PT J AU THEOCHARIS, SE MARGELI, AP TSOKOS, MG AF THEOCHARIS, SE MARGELI, AP TSOKOS, MG TI ALPHA(2B)-INTERFERON INHIBITS RAT-LIVER REGENERATION AFTER PARTIAL-HEPATECTOMY WITHOUT AFFECTING THYMIDINE KINASE-ACTIVITY SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID CELL NUCLEAR ANTIGEN; DAUDI CELLS; C-MYC; INTERFERON; PROLIFERATION; DNA; PROTOONCOGENES; EXPRESSION; INDUCTION; DIVISION AB The effect of alpha(2b)-interferon administration on liver regeneration after partial hepatectomy in male Wistar rats was examined 24 hours after the operation. Tritium thymidine incorporation into liver DNA, liver mass restitution, mitotic index, and nuclear expression of proliferating cell nuclear antigen were determined as indexes of hepatic proliferation. Both early and late alpha(2b)-interferon administration, 2 and 12 hours, respectively, after partial hepatectomy, at a dose of 3.3 x 10(4) IU per kg body weight, suppressed tritium thymidine incorporation and liver mass restitution (p < 0.001) when compared with that in untreated partially hepatectomized rats. The enzyme thymidine kinase (EC 2.7.1.21), a rate-determining enzyme of DNA biosynthesis, has been implicated in the suppression of proliferation in interferon-treated cell cultures. However, in the above-mentioned in vivo model of controlled cellular proliferation, thymidine kinase activity was not affected by alpha(2b)-interferon administration, whereas DNA biosynthesis was inhibited. These findings, in contrast to previous observations in in vitro models, show that the inhibition of the in vivo liver regeneration by alpha(2b)-interferon is not due to the inhibition of thymidine kinase activity. The expression of the cell cycle-related genes' products c-myc, p53, and c-erbB-2 proteins-which increase during the prereplicative phase that precedes DNA synthesis-was affected by interferon administration, being in accordance with liver proliferative status. C1 NIH,PATHOL LAB,BETHESDA,MD 20892. RP THEOCHARIS, SE (reprint author), UNIV ATHENS,SCH MED,DEPT EXPTL PATHOL,GR-11527 ATHENS,GREECE. NR 39 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAY PY 1995 VL 125 IS 5 BP 588 EP 596 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA QW171 UT WOS:A1995QW17100010 PM 7738425 ER PT J AU EDEN, GF STEIN, JF WOOD, MH WOOD, FB AF EDEN, GF STEIN, JF WOOD, MH WOOD, FB TI VERBAL AND VISUAL PROBLEMS IN READING-DISABILITY SO JOURNAL OF LEARNING DISABILITIES LA English DT Article ID ATTENTION DEFICIT DISORDER; EYE-MOVEMENTS; NORMAL READERS; DEVELOPMENTAL DYSLEXIA; LEARNING-DISABILITIES; NAMING DEFICITS; SEX-DIFFERENCES; LEVEL-MATCH; CHILDREN; HANDEDNESS AB Most individuals interested in reading disability favor the view that disordered language processing is the main cause of children's reading problems and that visual problems are seldom, if ever, responsible. Nevertheless, in a preliminary study (Eden, Stein, & Wood, 1993) we showed that visuospatial and oculomotor tests can be used to differentiate children with reading disabilities from nondisabled children. In the present study we investigated a larger sample of children to see if these findings held true. Using 93 children from the Bowman Gray Learning Disability Project (mean age = 11.3 years; 54 boys, 39 girls), we compared the phonological and visuospatial abilities of nondisabled children (children whose reading at fifth grade rated a Woodcock-Johnson reading standarized score between 85 and 115), and children with reading disability (whose reading standardized score was below 85 on the Woodcock-Johnson). In addition to performing poorly on verbal tests, the children with reading disability were significantly worse than nondisabled children at many visual and eye-movement tasks. A high proportion of the variance (68%) in reading ability of both the nondisabled children and those with reading disability could be predicted by combining visual and phonological scores in a multiple regression. These results provide further support for the hypothesis that reading disability may, to some extent, result from dysfunction of the visual and oculomotor systems. C1 UNIV OXFORD MAGDALEN COLL,OXFORD,ENGLAND. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,NEUROPSYCHOL SECT,WINSTON SALEM,NC 27103. RP EDEN, GF (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 86 TC 66 Z9 67 U1 9 U2 20 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 SN 0022-2194 J9 J LEARN DISABIL JI J. Learn. Disabil. PD MAY PY 1995 VL 28 IS 5 BP 272 EP 290 PG 19 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA QV338 UT WOS:A1995QV33800003 PM 7775847 ER PT J AU ERICKSON, KL BEUTLER, JA CARDELLINA, JH MCMAHON, JB NEWMAN, DJ BOYD, MR AF ERICKSON, KL BEUTLER, JA CARDELLINA, JH MCMAHON, JB NEWMAN, DJ BOYD, MR TI A NOVEL PHORBOL ESTER FROM EXCOECARIA-AGALLOCHA SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Note ID HIV-1 AB The novel phorbol ester 12-deoxyphorbol 13-(3E,5E-decadienoate) [1] was isolated as the anti-HIV principle of Excoecaria agallocha leaves and stems collected in northwest Australia. The structure was determined by spectral means. Compound 1 was also a potent displacer of [H-3]-phorbol dibutyrate from rat brain membranes. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,NAT PROD BRANCH,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 16 TC 42 Z9 51 U1 0 U2 3 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD MAY PY 1995 VL 58 IS 5 BP 769 EP 772 DI 10.1021/np50119a020 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA RG639 UT WOS:A1995RG63900020 PM 7623051 ER PT J AU GALBREATH, E KIM, SJ PARK, K BRENNER, M MESSING, A AF GALBREATH, E KIM, SJ PARK, K BRENNER, M MESSING, A TI OVEREXPRESSION OF TGF-BETA-1 IN THE CENTRAL-NERVOUS-SYSTEM OF TRANSGENIC MICE RESULTS IN HYDROCEPHALUS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ANIMAL MODEL; HYDROCEPHALUS; TRANSFORMING GROWTH FACTOR BETA-1 ID TRANSFORMING GROWTH-FACTOR; FIBRILLARY ACIDIC PROTEIN; MOLECULAR-WEIGHT COMPLEX; X-LINKED HYDROCEPHALUS; TGF-BETA RECEPTOR; HUMAN-PLATELETS; II RECEPTOR; RAT-BRAIN; CULTURED ASTROCYTES; EXPRESSION CLONING AB Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NINCDS,STROKE BRANCH,BETHESDA,MD 20892. RP GALBREATH, E (reprint author), UNIV WISCONSIN,SCH VET MED,DEPT PATHOBIOL SCI,2015 LINDEN DR W,MADISON,WI 53706, USA. FU NCRR NIH HHS [K01-RR00094] NR 92 TC 82 Z9 86 U1 1 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 339 EP 349 DI 10.1097/00005072-199505000-00007 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500007 PM 7745433 ER PT J AU SMITH, TW LIPPA, CF FLANDERS, KC SPORN, MB AF SMITH, TW LIPPA, CF FLANDERS, KC SPORN, MB TI TRANSFORMING GROWTH-FACTOR-BETA EXPRESSION IN NEURODEGENERATIVE DISEASES SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 445 EP 445 DI 10.1097/00005072-199505000-00151 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500150 ER PT J AU MCLEAN, CA MASTERS, CL VLADIMIRTSEV, VA PROKHOROVA, IA GOLDFARB, LG ASHER, DM ALEKSEEV, IP GAJDUSEK, DC AF MCLEAN, CA MASTERS, CL VLADIMIRTSEV, VA PROKHOROVA, IA GOLDFARB, LG ASHER, DM ALEKSEEV, IP GAJDUSEK, DC TI VILYUISK ENCEPHALITIS - MORPHOLOGIC SPECTRUM OF DISEASE, INCLUDING DEMYELINATION FOLLOWING SELF-INOCULATION WITH CEREBROSPINAL-FLUID SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV MELBOURNE,MELBOURNE,VIC,AUSTRALIA. VE RES CTR,SAKHA,RUSSIA. RUSSIAN ACAD SCI,MOSCOW,RUSSIA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 451 EP 451 DI 10.1097/00005072-199505000-00178 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500177 ER PT J AU MESSING, A DELANEY, CL BRENNER, M AF MESSING, A DELANEY, CL BRENNER, M TI CONDITIONAL ABLATION OF CEREBELLAR ASTROCYTES IN TRANSGENIC MICE SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 469 EP 469 DI 10.1097/00005072-199505000-00249 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500248 ER PT J AU WALKER, MF FITZGIBBON, EJ GOLDBERG, ME AF WALKER, MF FITZGIBBON, EJ GOLDBERG, ME TI NEURONS IN THE MONKEY SUPERIOR COLLICULUS PREDICT THE VISUAL RESULT OF IMPENDING SACCADIC EYE-MOVEMENTS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RESPONSE CHARACTERISTICS; PARIETAL CORTEX; BEHAVING MONKEY; ATTENTION; SPACE; CELLS; REPRESENTATION; ORGANIZATION; MODULATION; MACAQUE AB 1. Previous experiments have shown that visual neurons in the lateral intraparietal area (LIP) respond predictively to stimuli outside their classical receptive fields when an impending saccade will bring those stimuli into their receptive fields. Because LIP projects strongly to the intermediate layers of the superior colliculus, we sought to demonstrate similar predictive responses in the monkey colliculus. 2. We studied the behavior of 90 visually responsive neurons in the superficial and intermediate layers of the superior colliculus of two rhesus monkeys (Macaca mulatta) when visual stimuli or the locations of remembered stimuli were brought into their receptive fields by a saccade. 3. Thirty percent (18/60) of intermediate layer visuomovement cells responded predictively before a saccade outside the movement field of the neuron when that saccade would bring the location of a stimulus into the receptive field. Each of these neurons did not respond to the stimulus unless an eye movement brought it into its receptive field, nor did it discharge in association with the eye movement unless it brought a stimulus into its receptive field. 4. These neurons were located in the deeper parts of the intermediate layers and had relatively larger receptive fields and movement fields than the cells at the top of the intermediate layers. 5. The predictive responses of most of these neurons (16/18, 89%) did not require that the stimulus be relevant to the monkey's rewarded behavior. However, for some neurons the predictive response was enhanced when the stimulus was the target of a subsequent saccade into the neuron's movement field. 6. Most neurons with predictive responses responded with a similar magnitude and latency to a continuous stimulus that remained on after the saccade, and to the same stimulus when it was only flashed for 50 ms coincident with the onset of the saccade target and thus never appeared within the cell's classical receptive field. 7. The visual response of neurons in the intermediate layers of the colliculus is suppressed during the saccade itself. Neurons that showed predictive responses began to discharge before the saccade, were suppressed during the saccade, and usually resumed discharging after the saccade. 8. Three neurons in the intermediate layers responded tonically from stimulus appearance to saccade without a presaccadic burst. These neurons responded predictively to a stimulus that was going to be the target for a second saccade, but not to an irrelevant flashed stimulus. 9. No superficial layer neuron (0/27) responded predictively when a stimulus would be brought into their receptive fields by a saccade. This suggests that such responses will also not be found in the retina and striate and early prestriate visual cortex, which are the major sources of visual input to these layers. 10. For both superficial and intermediate layer neurons, the response to a stimulus flashed in the receptive field was stronger than the response of the neuron to the same stimulus brought into the receptive held by an eye movement (the reafferent response). 11. We suggest that the predictive response is caused by a transient shift in the retinal receptive field of the neuron, effected by a neural discharge corollary to the impending saccade. This mechanism enables the visual input to the saccadic system to compensate for eye movements and maintain a spatially accurate retinotopic representation of the visual world. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT NEUROL,WASHINGTON,DC 20007. NR 28 TC 219 Z9 219 U1 2 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1995 VL 73 IS 5 BP 1988 EP 2003 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QY833 UT WOS:A1995QY83300023 PM 7623096 ER PT J AU SATO, K KURATSU, JI TAKESHIMA, H YOSHIMURA, T USHIO, Y AF SATO, K KURATSU, JI TAKESHIMA, H YOSHIMURA, T USHIO, Y TI EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN MENINGIOMA SO JOURNAL OF NEUROSURGERY LA English DT Article DE MONOCYTE CHEMOATTRACTANT PROTEIN-1; MENINGIOMA; MACROPHAGE INFILTRATION; MESSENGER-RNA; IMMUNOHISTOCHEMISTRY ID HUMAN-BRAIN TUMORS; CHEMOTACTIC PROTEIN-1; HUMAN BASOPHILS; GENE JE; MCP-1; ACID; DEXAMETHASONE; MACROPHAGES; PRODUCT; GROWTH AB Monocyte chemoattractant protein-1 (MCP-1), purified from glioma cell line (U-105MG) culture fluid, attracts monocytes but not neutrophils. Macrophage accumulation is one of the pathological features of meningioma. To investigate the mechanism of macrophage infiltration into meningioma, the expression and localization of MCP-I in 16 cases of meningioma were studied using Northern blot analysis and immunohistochemistry. Seven of 16 meningiomas expressed MCP-1 messenger ribonucleic acid and protein, and some degree of macrophage infiltration was seen in all 16 meningiomas. There was a relationship between MCP-1 expression and the degree of macrophage infiltration; MCP-1 was strongly expressed in meningiomas with a high degree of macrophage infiltration. Sometimes the meningioma was accompanied by perifocal edema; a correlation between macrophage infiltration into brain tumors and perifocal edema has already been reported. It was found that the degree of MCP-1 expression is not correlated with the extent of perifocal edema. The authors' findings suggest that MCP-1 plays an important role in macrophage infiltration into meningioma. C1 NCI,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. RP SATO, K (reprint author), KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,1-1-1 HONJO,KUMAMOTO 860,JAPAN. NR 26 TC 33 Z9 37 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1995 VL 82 IS 5 BP 874 EP 878 DI 10.3171/jns.1995.82.5.0874 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QU325 UT WOS:A1995QU32500023 PM 7714614 ER PT J AU BACHARACH, SL BUVAT, I AF BACHARACH, SL BUVAT, I TI ATTENUATION CORRECTION IN CARDIAC POSITRON EMISSION TOMOGRAPHY AND SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE CARDIAC POSITION EMISSION TOMOGRAPHY; SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY; ATTENUATION CORRECTION ID NONUNIFORM ATTENUATION; SIMULTANEOUS TRANSMISSION; IMAGE-RECONSTRUCTION; SPECT RECONSTRUCTION; DETECTOR RESPONSE; PET TRANSMISSION; LINE SOURCE; COMPENSATION; ALGORITHMS; SCANS AB Quantitation in cardiac positron emission tomography (PET) and single-photon emission computed tomography (SPECT) depends on being able to correct for several physical factors that tend to distort the data, One of the most important of these corrections is the correction for attenuation. For PET, cardiac attenuation correction is a reality, although certain problems remain to be solved. For SPECT, recent developments in gamma camera hardware and reconstruction methods have finally made it possible to attempt attenuation correction in a clinical setting. This article reviews the methods available to perform attenuation correction in both PET and SPECT, with emphasis on the commonality between the problems encountered and solutions proposed for each modality. C1 INST GUSTAVE ROUSSY,INSERM,F-94805 VILLEJUIF,FRANCE. RP BACHARACH, SL (reprint author), NIH,BLDG 10,ROOM 1C401,10 CTR DR,MSC 1180,BETHESDA,MD 20892, USA. NR 58 TC 23 Z9 23 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 1995 VL 2 IS 3 BP 246 EP 255 DI 10.1016/S1071-3581(05)80062-5 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA RC295 UT WOS:A1995RC29500008 PM 9420795 ER PT J AU SUNG, C VANOSDOL, WW AF SUNG, C VANOSDOL, WW TI PHARMACOKINETIC COMPARISON OF DIRECT ANTIBODY TARGETING WITH PRETARGETING PROTOCOLS BASED ON STREPTAVIDIN-BIOTIN BINDING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PHARMACOKINETICS; MONOCLONAL ANTIBODIES; STREPTAVIDIN; BIOTIN; PRETARGETING ID MONOCLONAL-ANTIBODY; TUMORS; MODEL; BIODISTRIBUTION; CARCINOMA; TRANSPORT; HAPTENS; PROTEIN; TISSUES; FLUID AB Several groups are currently investigating antibody pretargeting as a strategy for improving radionuclide delivery. Pharmacokinetic modeling of these protocols permits analysis of pretargeting protocols under a broad range of possible experimental conditions. Methods: We used previously developed pharmacokinetic models to predict the temporal uptake and spatial distribution of directly radiolabeled MAb, radiolabeled biotin given after pretargeting with streptavidinylated MAb and radiolabeled streptavidin given after pretargeting with biotinylated MAb in a microscopic, prevascular tumor nodule. Two dose regimens were investigated, as were the effects of internalization and degradation of antibody-antigen complexes (24-hr time constant). Results: Simulations indicate that the protocol involving streptavidinylated MAb and radiolabeled biotin yields higher tumor-to-blood and tumor-to-lung ratios and relative exposures than the other protocols. In the absence of antigen internalization, the peak average molar concentration and MRT of biotin in the tumor nodule is comparable to that of directly radiolabeled MAb, and the spatial distribution of radionuclide is more uniform. When antigen internalization occurs, the peak average concentration and the MRT in the tumor nodule are lower than the corresponding values for directly radiolabeled MAb. Conclusion: In the absence of antigen internalization, the protocol involving streptavidinylated MAb and radiolabeled biotin offers pharmacokinetic advantages over the other two protocols. C1 HYBRITECH INC,SAN DIEGO,CA. RP SUNG, C (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. NR 31 TC 50 Z9 53 U1 1 U2 4 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 MAY PY 1995 VL 36 IS 5 BP 867 EP 876 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QW608 UT WOS:A1995QW60800033 PM 7738665 ER PT J AU ATKINSON, JC ROYCE, LS WELLNER, R PILLEMER, SR BERMUDEZ, D FOX, PC AF ATKINSON, JC ROYCE, LS WELLNER, R PILLEMER, SR BERMUDEZ, D FOX, PC TI ANTISALIVARY ANTIBODIES IN PRIMARY SJOGRENS-SYNDROME SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE AUTOANTIBODIES; SALIVARY GLANDS; SJOGRENS SYNDROME; SS-A/RO; SS-B/LA ID CELL-LINE; SS-A; GLAND; LA; FEATURES; PROTEINS; PARTICLE; RNA AB Earlier studies have described an antibody that recognized salivary ductal epithelium in sera from 15-50% of patients with primary Sjogren's syndrome; however, the specific salivary antigen in those studies was not identified The present study further investigated this unknown salivary antigen. Twenty-nine of 31 patients (94%) with primary Sjogren's syndrome demonstrated IgG antinuclear antibodies that bound to an epithelial cell line with ductal characteristics derived from a human salivary gland. Seventy-seven percent of these patients had serum antibodies that bound to ductal cells of normal human parotid tissue after formalin fixation. Western blots of cell extracts, immunofluorescence, and adsorption studies indicated that SS-A/Ro and SS-B/La were the antigens recognized in the salivary cell line. The pattern of fluorescence seen when anti-SS-B/La bound to normal parotid tissue was identical to the fluorescence pattern of the anti-salivary ductal antibodies described in earlier literature. C1 NIDR,CLIN INVEST SECT,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DIV PATHOPHYSIOL,FT DETRICK,MD 21702. NIAMSD,OFF PREVENT EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NR 25 TC 11 Z9 11 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 MAY PY 1995 VL 24 IS 5 BP 206 EP 212 DI 10.1111/j.1600-0714.1995.tb01168.x PG 7 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA QX631 UT WOS:A1995QX63100004 PM 7616459 ER PT J AU CONJEEVARAM, HS DIBISCEGLIE, AM AF CONJEEVARAM, HS DIBISCEGLIE, AM TI MANAGEMENT OF CHRONIC VIRAL-HEPATITIS IN CHILDREN SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review ID B VIRUS-INFECTION; CHRONIC DELTA-HEPATITIS; HBSAG-CARRIER CHILDREN; C VIRUS; SURFACE-ANTIGEN; ALPHA-INTERFERON; RECOMBINANT ALPHA-2-INTERFERON; HEPATOCELLULAR-CARCINOMA; INFANT TRANSMISSION; CHINESE PATIENTS RP CONJEEVARAM, HS (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 9C 103,BETHESDA,MD 20892, USA. NR 69 TC 14 Z9 14 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 1995 VL 20 IS 4 BP 365 EP 375 DI 10.1097/00005176-199505000-00001 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA QV948 UT WOS:A1995QV94800001 PM 7636678 ER PT J AU ABRAHAMSEN, TG LANGE, BJ PACKER, RJ VENZON, DJ ALLEN, JC CRAIG, CE PATRONAS, NJ KATZ, DA GOLDWEIN, JW DELANEY, TF REAMAN, GH PERILONGO, G PHILLIPS, PC OLDFIELD, EH POPLACK, DG HOROWITZ, ME AF ABRAHAMSEN, TG LANGE, BJ PACKER, RJ VENZON, DJ ALLEN, JC CRAIG, CE PATRONAS, NJ KATZ, DA GOLDWEIN, JW DELANEY, TF REAMAN, GH PERILONGO, G PHILLIPS, PC OLDFIELD, EH POPLACK, DG HOROWITZ, ME TI A PHASE-I AND PHASE-II TRIAL OF DOSE-INTENSIFIED CYCLOPHOSPHAMIDE AND GM-CSF IN PEDIATRIC MALIGNANT BRAIN-TUMORS SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE HIGH-DOSE INTENSITY CYCLOPHOSPHAMIDE; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; MALIGNANT GLIOMA; GLIOBLASTOMA; ASTROCYTOMA; PRIMITIVE NEUROECTODERMAL TUMOR; MEDULLOBLASTOMA; IMMUNOSUPPRESSION; THROMBOCYTOPENIA; PEDIATRIC ONCOLOGY ID COLONY-STIMULATING FACTOR; BONE-MARROW; CHEMOTHERAPY; VINCRISTINE; CHILDREN; THERAPY; INVIVO AB Purpose: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). Methods: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m(2)/day for 2 days i.v.; total dose 3.6-4.5 g/m(2)) was administered and was followed by recombinant human GM-CSF (5 mu g/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 X 10(9)/L. Results: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m(2)/week through cycle 2 (22 patients) to 0.8 g/m(2)/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of <0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. C1 TEXAS CHILDRENS HOSP,DEPT PEDIAT,HEMATOL ONCOL SECT,HOUSTON,TX 77030. NCI,PEDIAT BRANCH,BETHESDA,MD. NCI,DEPT DIAGNOST RADIOL,CTR CLIN,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20010. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. NYU,NEW YORK,NY. RI Venzon, David/B-3078-2008 NR 14 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY PY 1995 VL 17 IS 2 BP 134 EP 139 DI 10.1097/00043426-199505000-00006 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA QY931 UT WOS:A1995QY93100006 PM 7749762 ER PT J AU MUELLER, BU BURT, R GULICK, L JACOBSEN, F PIZZO, PA HORNE, M AF MUELLER, BU BURT, R GULICK, L JACOBSEN, F PIZZO, PA HORNE, M TI DISSEMINATED INTRAVASCULAR COAGULATION ASSOCIATED WITH GRANULOCYTE-COLONY-STIMULATING FACTOR THERAPY IN A CHILD WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF PEDIATRICS LA English DT Note ID NEUTROPENIA; TRIAL AB We report a case of disseminated intravascular coagulopathy, apparently caused by exposure to granulocyte colony-stimulating factor (G-CSF), The medical records of patients treated for more than 30 consecutive days with subcutaneously administered G-CSF were reviewed for the occurrence of thrombocytopenia or coagulation abnormalities, New-onset thrombocytopenia with a platelet count less than 100 X 10(9) cells/L (<100,000 cells/mm(3)) developed in 9 of 23 patients (39%) after a median of II weeks of treatment with G-CSF at dosages between 1 and 10 mu g/kg per day. C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT CLIN PATHOL, HEMATOL SERV, BETHESDA, MD 20892 USA. CHILDRENS MED CTR BROOKLYN, DEPT PEDIAT, BROOKLYN, NY USA. RP MUELLER, BU (reprint author), NCI, CLIN ONCOL PROGRAM, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NR 8 TC 5 Z9 5 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 MAY PY 1995 VL 126 IS 5 BP 749 EP 752 DI 10.1016/S0022-3476(95)70404-3 PN 1 PG 4 WC Pediatrics SC Pediatrics GA QY151 UT WOS:A1995QY15100012 PM 7538574 ER PT J AU ISHIDA, H KONDOH, T KATAOKA, M NISHIKAWA, S NAKAGAWA, T MORISAKI, I KIDO, JI OKA, T NAGATA, T AF ISHIDA, H KONDOH, T KATAOKA, M NISHIKAWA, S NAKAGAWA, T MORISAKI, I KIDO, JI OKA, T NAGATA, T TI FACTORS INFLUENCING NIFEDIPINE-INDUCED GINGIVAL OVERGROWTH IN RATS SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE GINGIVAL HYPERPLASIA ETIOLOGY; NIFEDIPINE ADVERSE EFFECTS ID CALCIUM-ANTAGONISTS; HYPERPLASIA; CYCLOSPORINE; APOPTOSIS; RECIPIENTS; PHENYTOIN; PLASMA AB FACTORS SUCH AS AGE, THE DOSE OF NIFEDIPINE ADMINISTERED in the diet, serum drug level, duration of drug administration, and sex which may influence nifedipine-induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90-days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg diet) increased the serum level of the drug in a dose-dependent manner in both males and females. However, a higher serum level was required in females than males to attain the same degree of gingival overgrowth. The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively, which gave respective minimum serum levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum concentration of the drug after it had reached the required minimum in male and female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was enough to induce maximal overgrowth, but this induction occurred only in rats that started to receive the drug when they were 20 days old, not in those that started at 50 and 90 days of age for the same administration period of 55 days, and the overgrowth regressed and the gingiva were normal 40 days after ceasing drug administration. These results suggest that gingival overgrowth occurred in accordance with the drug concentration in the diet, as well as that in the serum, and was more likely to occur in males and younger individuals. C1 OSAKA UNIV,FAC DENT,CLIN UNIT DENT HANDICAPPED,OSAKA,JAPAN. NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD. RP ISHIDA, H (reprint author), UNIV TOKUSHIMA,SCH DENT,DEPT PERIODONTOL & ENDOCRINOL,3-18-15 KURAMOTO CHO,TOKUSHIMA 770,JAPAN. NR 32 TC 27 Z9 30 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 1995 VL 66 IS 5 BP 345 EP 350 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RA937 UT WOS:A1995RA93700005 PM 7623253 ER PT J AU SHIPPENBERG, TS HEIDBREDER, C AF SHIPPENBERG, TS HEIDBREDER, C TI SENSITIZATION TO THE CONDITIONED REWARDING EFFECTS OF COCAINE - PHARMACOLOGICAL AND TEMPORAL CHARACTERISTICS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE SYSTEM; NUCLEUS-ACCUMBENS; RAT-BRAIN; RECEPTOR ANTAGONISTS; FRONTAL-CORTEX; AMPHETAMINE; MORPHINE; D-1; DRUG AB An unbiased place preference conditioning procedure was used to determine whether the repeated administration of cocaine results in sensitization to its conditioned rewarding effects. Rats received noncontingent injections of saline or cocaine (10 mg/kg i.p.) for 5 days. Place preference conditioning commenced 72 hr later. A minimum of three drug conditioning sessions was necessary for the establishment of cocaine-induced conditioned place preferences (CPP) in saline-pretreated rats. The minimum dose producing this effect was 10.0 mg/kg. In contrast, pre-exposure to cocaine resulted in significant place preferences occurring after only two drug conditioning sessions. Furthermore, CPP was observed in response to doses as low as 5.0 mg/kg. This shift in the cocaine dose-response curve was apparent when conditioning commenced either 3 or 7, but not 14, days after the cessation of cocaine pretreatment. An increased sensitivity to cocaine was also observed in rats which received only two cocaine (25.0 mg/kg) injections before conditioning and in those which had received either d-amphetamine (0.5 mg/kg) or morphine (5.0 mg/kg) for 5 days. Repeated administration of the D1 dopamine (DA) receptor antagonist, SCH-23390 (0.01-0.05 mg/kg), or the D2 antagonist, raclopride (0.1-1.0 mg/kg), for 5 days did not modify cocaine-induced place conditioning. Administration of SCH-23390 (0.05 mg/kg) in combination with cocaine, however, prevented the sensitized response to cocaine. In contrast, raclopride did not influence the sensitized response to cocaine. These data demonstrate that sensitization occurs to the conditioned rewarding effects of cocaine and suggest an involvement of D1 DA receptors in the development of this phenomenon. RP SHIPPENBERG, TS (reprint author), NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 60 TC 214 Z9 214 U1 1 U2 8 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 MAY PY 1995 VL 273 IS 2 BP 808 EP 815 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX925 UT WOS:A1995QX92500034 PM 7752084 ER PT J AU HOROWITZ, S MAZOR, M ROMERO, R HOROWITZ, J GLEZERMAN, M AF HOROWITZ, S MAZOR, M ROMERO, R HOROWITZ, J GLEZERMAN, M TI INFECTION OF THE AMNIOTIC CAVITY WITH UREAPLASMA-UREALYTICUM IN THE MIDTRIMESTER OF PREGNANCY SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE UREAPLASMA UREALYTICUM; AMNIOTIC FLUID; PREGNANCY COMPLICATIONS; PREGNANCY, 2ND TRIMESTER ID PRETERM LABOR; INTRAAMNIOTIC INFECTION; MYCOPLASMA-HOMINIS; FLUID INFECTION; MEMBRANES; WOMEN AB The purpose of this study was to determine the clinical significance of invasion of the amniotic fluid (AF) with Ureaplasma urealyticum in the midtrimester of pregnancy. Amniotic fluid and cervical swabs obtained from 214 asymptomatic women in the midtrimester of pregnancy (16-20 weeks) were cultured for U urealyticum and Mycoplasma hominis. Inoculum size was determined by quantitative culture. Six of the 214 women (2.8%) had Ureaplasma in high titers in the AF. The pregnancy outcomes of 129 women were determined. Adverse pregnancy outcome occurred more frequently in women with a positive AF culture than in women with a negative AF culture (3/6 [50%] vs. 15/123 [12%], respectively; P = .035). We conclude that infection of the amniotic cavity with U urealyticum can be present in asymptomatic patients in the midtrimester of pregnancy and is a significant risk factor for spontaneous preterm labor and delivery. These observations suggest that routine culture of AF at the time of midtrimester amniocentesis can identify the group of patients at risk for a poor pregnancy outcome. C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DETROIT,MI 48201. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. NICHHD,DEPT OBSTET & GYNECOL,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT OBSTET & GYNECOL,IL-84105 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT MED A,IL-84105 BEER SHEVA,ISRAEL. RP HOROWITZ, S (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT IMMUNOL & MICROBIOL,IL-84105 BEER SHEVA,ISRAEL. NR 21 TC 79 Z9 82 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 1995 VL 40 IS 5 BP 375 EP 379 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QY127 UT WOS:A1995QY12700010 PM 7608879 ER PT J AU JANOFF, HB TABAS, JA SHORE, EM MUENKE, M DALINKA, MK SCHLESINGER, S ZASLOFF, MA KAPLAN, FS AF JANOFF, HB TABAS, JA SHORE, EM MUENKE, M DALINKA, MK SCHLESINGER, S ZASLOFF, MA KAPLAN, FS TI MILD EXPRESSION OF FIBRODYSPLASIA OSSIFICANS PROGRESSIVA - A REPORT OF 3 CASES SO JOURNAL OF RHEUMATOLOGY LA English DT Note DE FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; HETEROTOPIC OSSIFICATION AB We describe 3 unusually mild cases of fibrodysplasia ossificans progressiva (FOP) in an 80-year-old man, a 44-year-old woman, and a 17-year-old woman. The man, whose daughter had classic features of FOP, lacked malformation of the great toes and experienced unusually slow progression of the disease. Both women displayed late onset heterotopic ossification, The older woman displayed an unusually slow progression of the disease. All 3 patients remained ambulatory at the time of examination. Recognition of a mild form of FOP will influence diagnosis, counselling, and research in this rare condition. C1 UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT RADIOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19104. NIH,DEPT MED GENET,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT ORTHOPAED SURG,DIV MOLEC ORTHOPAED,PHILADELPHIA,PA 19104. RI Shore, Eileen/D-2593-2009 NR 15 TC 15 Z9 16 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1995 VL 22 IS 5 BP 976 EP 978 PG 3 WC Rheumatology SC Rheumatology GA QY836 UT WOS:A1995QY83600031 PM 8587093 ER PT J AU HABERMAN, PW NOBLE, JA DUFOUR, MC AF HABERMAN, PW NOBLE, JA DUFOUR, MC TI ALCOHOL-USE IN COMBINATION WITH COCAINE, HEROIN AND METHADONE BY MEDICAL EXAMINER CASES SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID NEW-YORK-CITY; COUNTY; DEATH; PREVALENCE; FATALITIES; HOMICIDE; DRIVERS; ABUSE; DRUGS AB Objective: The purpose of this review of all appropriate, available medical examiner (ME) studies is to provide information on cases with positive toxicologies for cocaine, morphine (the heroin metabolite) and methadone that have positive blood or brain alcohol concentrations (BACs). Method: Criteria for inclusion of U.S. ME studies in this review are (1) at least 20 cases with a positive toxicology for cocaine, morphine or methadone and (2) BAC test findings according to specific drug positivity. Only 19 studies conducted from 1969 to 1992 met these criteria; most studies reviewed were not included primarily because of their failure to present or link available BAC test findings with positive toxicologies for these other drugs. Results: The BAG-positive ranges were similar for cocaine and heroin. In reports on both heroin and methadone or on all three drugs, heroin-positive cases had the highest proportions and methadone-positive cases had the lowest proportions with positive BACs. Conclusion: Published data confirm the substantial presence of alcohol in combination with cocaine, heroin and methadone among ME cases. Future ME studies should endeavor to link BAC and toxicology findings for other drugs according to drug-induced or drug-related manner of death. These data would advance our knowledge about the role of alcohol in drug deaths and provide additional information on substance abuse trends. RP HABERMAN, PW (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 28 TC 16 Z9 16 U1 0 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAY PY 1995 VL 56 IS 3 BP 344 EP 347 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QV171 UT WOS:A1995QV17100014 PM 7623474 ER PT J AU BARRICKMAN, LL PERRY, PJ ALLEN, AJ KUPERMAN, S ARNDT, SV HERRMANN, KJ SCHUMACHER, E AF BARRICKMAN, LL PERRY, PJ ALLEN, AJ KUPERMAN, S ARNDT, SV HERRMANN, KJ SCHUMACHER, E TI BUPROPION VERSUS METHYLPHENIDATE IN THE TREATMENT OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ATTENTION-DEFICIT HYPERACTIVITY DISORDER; PHARMACOTHERAPY; BUPROPION; METHYLPHENIDATE ID DEPRESSED-PATIENTS; CONTROLLED TRIAL; CHILDREN; IMIPRAMINE; EFFICACY; DELIRIUM; DESIPRAMINE AB Objective: In the treatment of attention-deficit hyperactivity disorder (ADHD), the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants (methylphenidate and/or dextroamphetamine). However, the effectiveness of bupropion has been contrasted only with placebo. The primary aim of this study was to contrast the efficacy of bupropion with that of methylphenidate in the treatment of ADHD. Method: A double-blind, crossover design was used in this study. After a 14-day medication washout period, 15 ADHD subjects (7 to 17 years old) were randomized to either methylphenidate or bupropion for 6 weeks, washed out for an additional 2 weeks, and then ''crossed over'' to the other drug. Methylphenidate was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day (mean 0.7 mg/kg per day) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day (mean 3.3 mg/kg per day). Results: Both methylphenidate and bupropion produced significantly greater (p<.001) and equivalent improvement on the Iowa-Conners Teacher's Rating Scale according to both the subjects' parents and teachers. The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale, Kagan's Matching Familiar Figures Test, Continuous Performance Test, Children's Depression Inventory, Children's Manifest Anxiety Scale, and Rey Auditory-Verbal Learning Test. Conclusions: In this double-blind, crossover trial, bupropion and methylphenidate were both effective and did not differ in their overall efficacy as treatments for ADHD. C1 MESA MENTAL HLTH CORP,ALBUQUERQUE,NM. UNIV IOWA,COLL PHARM,IOWA CITY,IA 52242. NIMH,WASHINGTON,DC 20032. UNIV WISCONSIN,COLL MED,DEPT PSYCHIAT,MADISON,WI 53706. DUKE UNIV,DEPT PSYCHOL,DURHAM,NC 27706. RP BARRICKMAN, LL (reprint author), UNIV IOWA,COLL MED,DEPT PSYCHIAT,DIV CHILD PSYCHIAT,2271 QUADRANGLE,IOWA CITY,IA 52242, USA. RI Arndt, Stephan/A-6976-2013 OI Arndt, Stephan/0000-0003-0783-8204 NR 42 TC 158 Z9 161 U1 3 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1995 VL 34 IS 5 BP 649 EP 657 DI 10.1097/00004583-199505000-00017 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QV536 UT WOS:A1995QV53600017 PM 7775360 ER PT J AU BENVENUTI, F FERRUCCI, L GURALNIK, JM GANGEMI, S BARONI, A AF BENVENUTI, F FERRUCCI, L GURALNIK, JM GANGEMI, S BARONI, A TI FOOT PAIN AND DISABILITY IN OLDER PERSONS - AN EPIDEMIOLOGIC SURVEY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ELDERLY PERSONS; COMMUNITY; ILLNESS; HEALTH AB OBJECTIVE: To investigate the prevalence of foot pain in older people and its association with pathological conditions of the feet and with disability in basic and instrumental activities of daily living. DESIGN: Cross-sectional survey of a community-dwelling older population. PARTICIPANTS: A total of 459 subjects, 73% of the population aged 65 years and older living in Dicomano, Florence, Italy. MEASUREMENTS: A standardized medical examination was performed by a geriatrician to collect information on the presence of pain, specific problems of the feet, gait, and several indicators of physical health status. Disability in basic and instrumental activities of daily living was evaluated by self-report. RESULTS: The prevalence of foot pain was very high, especially in subjects affected by calluses or corns, hallux deformities, hammer toes, pes planus, and edema and among those who complained of difficulty in looking after the basic needs of the feet. Patients with foot pain needed a greater number of steps and longer time to walk the same distance. Foot pain was associated with a higher prevalence of disability in instrumental activities of daily living, particularly those related to standing and ambulation capacities, but it was not related to higher prevalence of disability in basic activities of daily living. CONCLUSIONS: Foot pain is associated with specific conditions of the feet and disability in instrumental activities of daily living. Adequate assessment and treatment of foot problems may prevent foot pain and potentially reduce risk of disability. This hypothesis needs to be tested in longitudinal studies and specific intervention trials. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD. RP BENVENUTI, F (reprint author), INRCA FLORENCE,OSPED I FRATICINI,DEPT GERIATR,CTR GERIATR,VIA MASSONI 21,I-50139 FLORENCE,ITALY. NR 28 TC 151 Z9 157 U1 1 U2 12 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 MAY PY 1995 VL 43 IS 5 BP 479 EP 484 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QW688 UT WOS:A1995QW68800003 PM 7730527 ER PT J AU HODES, RJ LAKATTA, EG MCNEIL, CT AF HODES, RJ LAKATTA, EG MCNEIL, CT TI ANOTHER MODIFIABLE RISK FACTOR FOR CARDIOVASCULAR-DISEASE - SOME EVIDENCE POINTS TO ARTERIAL STIFFNESS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID AGE RP HODES, RJ (reprint author), NIA,OFF DIRECTOR,BLDG 31,RM 5C35,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 74 Z9 76 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 MAY PY 1995 VL 43 IS 5 BP 581 EP 582 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QW688 UT WOS:A1995QW68800022 PM 7730544 ER PT J AU LINDBERG, DAB HUMPHREYS, BL AF LINDBERG, DAB HUMPHREYS, BL TI THE HIGH-PERFORMANCE COMPUTING AND COMMUNICATIONS PROGRAM, THE NATIONAL INFORMATION INFRASTRUCTURE, AND HEALTH-CARE SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review AB The High-Performance Computing and Communications (HPCC) program is a multiagency federal effort to advance the state of computing and communications and to provide the technologic platform on which the National Information Infrastructure (NII) can be built. The HPCC program supports the development of high-speed computers, high-speed telecommunications, related software and algorithms, education and training, and information infrastructure technology and applications. The vision of the NII is to extend access to highperformance computing and communications to virtually every U.S. citizen so that the technology can be used to improve the civil infrastructure, lifelong learning, energy management, health care, etc. Development of the NII will require resolution of complex economic and social issues, including information privacy. Health-related applications supported under the HPCC program and NII initiatives include connection of health care institutions to the Internet; enhanced access to gene sequence data; the ''Visible Human'' Project; and test-bed projects in telemedicine, electronic patient records, shared informatics tool development, and image systems. RP LINDBERG, DAB (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BLDG 38,ROOM 2W04,BETHESDA,MD 20894, USA. NR 17 TC 16 Z9 18 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 1995 VL 2 IS 3 BP 156 EP 159 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA QW173 UT WOS:A1995QW17300002 PM 7614116 ER PT J AU LINDBERG, DAB HUMPHREYS, BL AF LINDBERG, DAB HUMPHREYS, BL TI HIGH-PERFORMANCE COMPUTING AND COMMUNICATIONS AND THE NATIONAL INFORMATION INFRASTRUCTURE - NEW OPPORTUNITIES AND CHALLENGES SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material RP LINDBERG, DAB (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BLDG 38,ROOM 2W04,BETHESDA,MD 20894, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 1995 VL 2 IS 3 BP 197 EP 197 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA QW173 UT WOS:A1995QW17300007 PM 7614121 ER PT J AU SMITH, RA BALIS, FM OTT, KH ELSBERRY, DD SHERMAN, MR SAIFER, MGP AF SMITH, RA BALIS, FM OTT, KH ELSBERRY, DD SHERMAN, MR SAIFER, MGP TI PHARMACOKINETICS AND TOLERABILITY OF VENTRICULARLY ADMINISTERED SUPEROXIDE-DISMUTASE IN MONKEYS AND PRELIMINARY CLINICAL OBSERVATIONS IN FAMILIAL ALS SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 5th International Symposium on MND/ALS CY NOV 07-09, 1994 CL NOORDWIJK, NETHERLANDS SP Int Alliance Motor Neurone Dis Assoc DE AMYOTROPHIC LATERAL SCLEROSIS; CEREBROSPINAL FLUID; INTRACEREBROVENTRICULAR INFUSION; MUSCLE; NEURODEGENERATION; ORGOTEIN; SUPEROXIDE DISMUTASE ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR NEURON DISEASE; CEREBROSPINAL-FLUID; BRAIN AB The discovery of mutations in the gene for Cu/Zn superoxide dismutase (SOD) in some cases of familial amyotrophic lateral sclerosis (FALS) provides a rationale for enzyme replacement therapy. The inability of SOD to cross the blood-brain barrier motivated this study of the safety, tolerability and pharmacokinetics of bovine SOD (bSOD) administered into the CSF of rhesus monkeys and one late-stage, SOD-deficient FALS patient. Kinetic analyses in the patient indicated that intracerebroventricular (i.c.v.) administration, but not lumbar administration, delivered bSOD to the entire CSF pathway. Daily bolus i.c.v. injections (32 mg/day) and continuous i.c.v. infusion (30 mg/day) were well tolerated by the patient. During the period of daily bolus injections, the patient's performance on manual muscle tests was nearly stable, in contrast with the rapid decline before and after that period. These results justify further investigation of bSOD therapy in SOD-deficient FALS patients. C1 CTR NEUROL STUDY,SAN DIEGO,CA 92121. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. MEDTRONIC INC,MINNEAPOLIS,MN 55421. OXIS INT INC,MT VIEW,CA 94043. NEUROSURG MED CLIN INC,LA JOLLA,CA 92037. NR 38 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY PY 1995 VL 129 SU S BP 13 EP 18 DI 10.1016/0022-510X(95)00051-3 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RK085 UT WOS:A1995RK08500004 PM 7595604 ER PT J AU GHEZZI, F GHIDINI, A ROMERO, R GOMEZ, R GALASSO, M COHEN, J TREADWELL, MC AF GHEZZI, F GHIDINI, A ROMERO, R GOMEZ, R GALASSO, M COHEN, J TREADWELL, MC TI DOPPLER VELOCIMETRY OF THE FETAL MIDDLE CEREBRAL-ARTERY IN PATIENTS WITH PRETERM LABOR AND INTACT MEMBRANES SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE PULSATILITY INDEX; MIDDLE CEREBRAL ARTERY; PRETERM LABOR ID FLOW VELOCITY WAVEFORMS; GROWTH-RETARDED FETUSES; BLOOD-FLOW; WAVE-FORMS; DECELERATIONS; PREGNANCIES AB A prospective cohort study was conducted to determine whether preterm labor is associated with changes in the impedance to blood flow of the fetal middle cerebral artery. Doppler velocimetry studies were performed in 194 consecutive patients with preterm labor and intact membranes. Pulsatility indices of the middle cerebral artery and umbilical artery were determined on admission. Results were expressed as ratio of the observed pulsatility index to mean value for gestational age expressed as Delta MCA PI and Delta UA PI, respectively. The prevalence of preterm delivery (< 37 weeks) and delivery within 24 hours of admission was 55.2% (107/194) and 15.5% (30/194), respectively. Patients with an examination-to-delivery interval within 24 hours had significantly lower mean Delta MCA PI than that of patients delivered at greater than or equal to 37 weeks and greater than or equal to 4 weeks after the examination (P < 0.01). Fetuses with a Delta MCA PI at or below 0.88 had a relative risk of 2 (95% confidence interval, 1.32 to 2.9) who were delivered within 24 hours compared to controls (sensitivity 76.7%, specificity 62.8%, positive predictive value 26.7%, negative predictive value 93.5%). Stepwise logistic regression analysis indicated that the relationship between Delta MCA PI and examination-to-delivery interval remained statistically significant after correcting for cervical dilatation (P < 0.001). Our data indicate that preterm parturition is associated with a decrease in the impedance to flow in the fetal cerebral circulation. C1 NICHHD,DEPT OBSTET & GYNECOL,DIV INTRAMURAL,PERINATOL RES BRANCH,WASHINGTON,DC 20007. WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 19 TC 12 Z9 13 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAY PY 1995 VL 14 IS 5 BP 361 EP 366 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA QY602 UT WOS:A1995QY60200007 PM 7609014 ER PT J AU MYERS, RB SRIVASTAVA, S GRIZZLE, WE AF MYERS, RB SRIVASTAVA, S GRIZZLE, WE TI LEWIS-Y ANTIGEN AS DETECTED BY THE MONOCLONAL-ANTIBODY BR96 IS EXPRESSED STRONGLY IN PROSTATIC ADENOCARCINOMA SO JOURNAL OF UROLOGY LA English DT Article DE ANTIBODIES, NEOPLASM; PROSTATIC NEOPLASMS; ADENOCARCINOMAS; ANTIGENS, NEOPLASM ID ANTITUMOR-ACTIVITY; CANCER AB We used the monoclonal antibody BR96 to determine the expression of the Lewis Y antigen in benign and malignant prostatic tissues. Strong immuno-staining was detected within the basal cells of benign glands in 29 of 30 specimens examined. In contrast, weak immune-staining of the secretory (luminal) epithelium was detected in only 10 of these same 30 specimens. Moderate to strong immuno-staining of luminal cells, however, was observed in prostatic intraepithelial neoplasia in 15 of 17 specimens. Immune-staining was detected within the malignant cells in all 49 specimens of primary prostatic adenocarcinoma examined. We used a semiquantitative technique to compare the extent of immune-staining among well (combined Gleason score less than 6), moderately (combined Gleason score 6 to 7) and poorly (combined Gleason score more than 7) differentiated tumors as well as metastatic lesions. Poorly differentiated tumors demonstrated the greatest extent of immune-staining compared to moderately and well differentiated adenocarcinoma. Strong immune-staining was also detected within the malignant cells in 7 metastatic (5 nodal lesions and 2 bone marrow biopsies) tumors. The extent of immune-staining in the metastatic lesions was similar to that observed in the poorly differentiated primary tumors. In summary, the Lewis Y antigen, as detected by BR96, is widely expressed within prostatic adenocarcinomas. Furthermore, the poorly differentiated as well as metastatic lesions frequently demonstrated the highest expression of the Lewis Y antigen. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CN-15340-02] NR 16 TC 33 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1995 VL 153 IS 5 BP 1572 EP 1574 DI 10.1016/S0022-5347(01)67464-0 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA QR574 UT WOS:A1995QR57400060 PM 7714977 ER PT J AU GOLDSTEIN, S HAGUE, B MONTEFIORI, D HIRSCH, VM AF GOLDSTEIN, S HAGUE, B MONTEFIORI, D HIRSCH, VM TI A MACAQUE ADHERENT CELL-LINE THAT EXPRESSES HUMAN CD4 IS SUSCEPTIBLE TO SIV - UTILITY FOR ASSESSING NEUTRALIZING ANTIBODY SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE MACAQUE MAMMARY TUMOR CELL LINE; CD4; SIV; AIDS ID SIMIAN IMMUNODEFICIENCY VIRUS; CONFERS PROTECTION; PROVIRAL DNA; INFECTION; VACCINE; MONKEYS; DISEASE AB A macaque CD4+ adherent cell line was generated by stable expression of the human CD4 gene in a rhesus macaque mammary tumor cell line, CMMT. The resulting cell line CMMT/CD4 expressed surface CD4 and was sensitive to infection by a wide range of isolates of simian immunodeficiency virus (SIV) of different subgroups, but was not susceptible to infection with HIV-1. The CMMT/CD4 cell line was used to develop a microassay for measurement of neutralizing antibody in plasma of SIV-infected or immunized animals. Single infected cells could be detected in a monolayer of CMMT/CD4 by immunoperoxidase and a 90% reduction in the number of positive cells was used as a measure of neutralizing activity of two-fold plasma dilutions. This assay had comparable sensitivity to methods based upon detecting a reduction in reverse transcriptase activity of SIV, reduction of viral antigen, or inhibition of cytopathic effect. C1 NIAID,LID,IMMUNODEFICIENCY VIRUSES SECT,ROCKVILLE,MD 20852. NIAID,LIG,ROCKVILLE,MD 20852. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 1995 VL 53 IS 1 BP 139 EP 148 DI 10.1016/0166-0934(95)00010-R PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA QZ253 UT WOS:A1995QZ25300014 PM 7635923 ER PT J AU ENGELMAN, A ENGLUND, G ORENSTEIN, JM MARTIN, MA CRAIGIE, R AF ENGELMAN, A ENGLUND, G ORENSTEIN, JM MARTIN, MA CRAIGIE, R TI MULTIPLE EFFECTS OF MUTATIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE ON VIRAL REPLICATION SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; MURINE LEUKEMIA-VIRUS; DNA-BINDING; ESCHERICHIA-COLI; PROTEIN INVITRO; CELL-LINE; IDENTIFICATION; MUTAGENESIS; RETROVIRUS; CLEAVAGE AB The integration of a DNA copy of the human immunodeficiency virus type 1 (HIV-1) genome into a chromosome of an infected cell is a pivotal step in virus replication. Integration requires the activity of the virus-encoded integrase, which enters the cell as a component of the virion. Results of numerous mutagenesis studies have identified amino acid residues and protein domains of HIV-1 integrase critical for in vitro activity, but only a few of these mutants have been studied for their effects on HIV replication. We have introduced site-directed changes into an infectious DNA clone of HIV-1 and show that integrase mutations can affect virus replication at a variety of steps. We identified mutations that altered virion morphology, levels of particle-associated integrase and reverse transcriptase, and viral DNA synthesis. One replication-defective mutant virus which had normal morphology and protein composition displayed increased levels of circular viral DNA following infection of a T-cell line. This virus also had a significant titer in a CD4-positive indicator cell assay, which requires the viral Tat protein. Although unintegrated viral DNA can serve as a template for Tat expression in infected indicator cells, this level of expression is insufficient to support a spreading viral infection in CD4-positive lymphocytes. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC 20037. NR 58 TC 332 Z9 342 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 2729 EP 2736 PG 8 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400002 PM 7535863 ER PT J AU WANG, K KRAUSE, PR STRAUS, SE AF WANG, K KRAUSE, PR STRAUS, SE TI ANALYSIS OF THE PROMOTER AND CIS-ACTING ELEMENTS REGULATING EXPRESSION OF HERPES-SIMPLEX VIRUS TYPE-2 LATENCY-ASSOCIATED TRANSCRIPTS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; HUMAN SENSORY GANGLIA; IMMEDIATE EARLY GENE; LAT PROMOTER; LOCATED UPSTREAM; RESPONSE ELEMENT; MESSENGER-RNA; CYCLIC-AMP; SEQUENCE; REACTIVATION AB In latently infected neurons, herpes simplex virus type 2 (HSV-2) expresses one abundant family of transcripts, the latency-associated transcripts (LATs). We demonstrate here that the sequence lying about 700 bp upstream of the 5' end of the HSV-2 major LAT acts as a very strong promoter in transient expression assays in both neuronal and nonneuronal cells. Transcription starts about 27 to 32 bp downstream of a functional TATA box. The proximal fragment from -102 to +34 includes the basal promoter and accounts for constitutive transcriptional activity in various cell lines. The distal region from -392 to -103 contributes to particularly strong promoter activity in neuronal cell lines and involves multiple cis-acting elements. A functional activating transcription factor/cyclic AMP (cAMP) response element binding protein motif lies just upstream of the TATA. By DNase I footprint and methylation protection assays, we identified several additional protein-binding sites upstream of the activating transcription factor/cAMP response element binding protein motif. A GC-rich element, termed LAT-3, was located between bases -128 to -102. A 2-bp substitution in LAT-3 markedly reduced promoter activity and abolished protein-binding ability in vitro. Gel retardation assay showed no competition for protein binding to LAT-3 by other GC-rich elements. LAT-3 appears to be a novel cis-acting element that may contribute to the neuronal responsiveness of the HSV-2 LAT promoter. C1 USDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. RP WANG, K (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 42 TC 8 Z9 9 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 MAY PY 1995 VL 69 IS 5 BP 2873 EP 2880 PG 8 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400021 PM 7707511 ER PT J AU CHERNOMORDIK, L LEIKINA, E CHO, MS ZIMMERBERG, J AF CHERNOMORDIK, L LEIKINA, E CHO, MS ZIMMERBERG, J TI CONTROL OF BACULOVIRUS GP64-INDUCED SYNCYTIUM FORMATION BY MEMBRANE LIPID-COMPOSITION SO JOURNAL OF VIROLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; HEXAGONAL PHASE-TRANSITION; NUCLEAR POLYHEDROSIS-VIRUS; INTACT HUMAN-ERYTHROCYTES; PH-DEPENDENT FUSION; ACYL CHAIN LENGTHS; FATTY-ACIDS; CONFORMATIONAL CHANGE; BIOLOGICAL-MEMBRANES; LATERAL MOBILITY AB We have investigated the effects of membrane lipid composition on biological membrane fusion triggered by low pH and mediated by the baculovirus envelope glycoprotein gp64. Lysolipids, either added exogenously or produced in situ by phospholipase A2 treatment of cell membranes, reversibly inhibited syncytium formation. Lysolipids also decreased the baculovirus infection rate. In contrast, oleic and arachidonic acids and mono-olein promoted cell-cell fusion. Membrane lipid composition affected pH-independent processes which followed the low-pH-induced change in fusion protein conformation. Inhibition and promotion of membrane fusion by a number of lipids could not be explained by mere binding or incorporation into membranes, but rather was correlated with the effective molecular shape of exogenous lipids. Our data are consistent with the hypothesis that membrane fusion proceeds through highly bent membrane intermediates (stalks) having a net negative curvature. Consequently, inverted cone-shaped lysolipids inhibit and cone-shaped cis-unsaturated fatty acids promote stalk formation and, ultimately, membrane fusion. RP CHERNOMORDIK, L (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 63 TC 68 Z9 70 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 MAY PY 1995 VL 69 IS 5 BP 3049 EP 3058 PG 10 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400042 PM 7707532 ER PT J AU ARTHUR, LO BESS, JW URBAN, RG STROMINGER, JL MORTON, WR MANN, DL HENDERSON, LE BENVENISTE, RE AF ARTHUR, LO BESS, JW URBAN, RG STROMINGER, JL MORTON, WR MANN, DL HENDERSON, LE BENVENISTE, RE TI MACAQUES IMMUNIZED WITH HLA-DR ARE PROTECTED FROM CHALLENGE WITH SIMIAN IMMUNODEFICIENCY VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-II HISTOCOMPATIBILITY; WHOLE SIV VACCINE; ENVELOPE GLYCOPROTEIN; INACTIVATED VIRUS; MEMBRANE-PROTEINS; RHESUS MACAQUES; LEUKEMIA-VIRUS; HUMAN-CELLS; INFECTION; ANTIGENS AB Macaques immunized with uninfected human cells have been shown to be protected from challenge with simian immunodeficiency virus (SN) propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells, sucrose density gradient-purified culture fluid from uninfected human cells (mock virus), beta-2 microglobulin (beta 2M), immunoaffinity-purified HLA class I and class II proteins from these human cells, and adjuvant. Although all macaques immunized with beta 2M and HLA class I developed high antibody titers to beta 2M, these animals were not protected from a subsequent challenge with infectious SIV grown in human cells. In contrast, the macaques immunized with class II protein (HLA DR) and mock virus developed antibodies to class II protein and were protected from the intravenous infectious virus challenge. The class II protein- and mock virus-immunized animals which were protected from challenge were given boosters of the appropriate antigen and challenged with the same SIV propagated in macaque cells. All animals became infected, indicating that the protection seen with human class II protein did not extend to protection from infection with SIV containing macaque class II proteins. Since the virus released from SIV-infected macaque cells would contain macaque class II proteins, our results suggest that the initial SIV infected was completely prevented. In addition, the lack of protection from challenge with SIV propagated in macaque cells provided strong evidence that the protection was due to an immune response to the cellular proteins and not to epitopes cross-reactive between class II proteins and the viral proteins, since the identical virus proteins were present in both challenge stocks. These results are the first demonstration that immunization with a purified cellular protein can protect from virus infection. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. RP ARTHUR, LO (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-74102] NR 59 TC 116 Z9 117 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 MAY PY 1995 VL 69 IS 5 BP 3117 EP 3124 PG 8 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400050 PM 7707540 ER PT J AU ENGLUND, G THEODORE, TS FREED, EO ENGELMAN, A MARTIN, MA AF ENGLUND, G THEODORE, TS FREED, EO ENGELMAN, A MARTIN, MA TI INTEGRATION IS REQUIRED FOR PRODUCTIVE INFECTION OF MONOCYTE-DERIVED MACROPHAGES BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Note ID MONONUCLEAR PHAGOCYTES; HIV-1 INFECTION; GENE-EXPRESSION; DNA-BINDING; INVITRO; PROTEIN; IDENTIFICATION; MUTAGENESIS; REGION; CELLS AB Certain human immunodeficiency virus type 1 (HIV-1) isolates are able to productively infect nondividing cells of the monocyte/macrophage lineage. We have used a molecular genetic approach to construct two different HIV-1 integrase mutants that were studied in the contest of an infectious, macrophage-tropic HIV-1 molecular clone. One mutant, HIV-1(Delta D(35)E), containing a 37-residue deletion within the central, catalytic domain of integrase, was noninfectious in both peripheral blood mononuclear cells and monocyte-derived macrophages. The HIV-1(Delta D(35)E), mutant, however, exhibited defects in the assembly and/or release of progeny virions in transient transfection assays, as well as defects in entry and/or viral DNA synthesis during the early stages of monocyte-derived macrophage infection. The second mutant, HIV-1(D116N/8), containing a single Asp-to-Asn substitution at the invariant Asp-116 residue of integrase, was also noninfectious in both peripheral blood mononuclear cells and monocyte-derived macrophages but, in contrast to HIV-1(Delta D(35)E), was indistinguishable from wild-type virus in reverse transcriptase production. PCR analysis indicated that HIV-1(D116N/8) entered monocyte-derived macrophages efficiently and reverse transcribed its RNA but was unable to complete its replication cycle because of a presumed block to integration, These data are consistent with the hypothesis that integration is an obligate step in productive HIV-1 infection of activated peripheral blood mononuclear cells and primary human macrophage cultures. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 36 TC 111 Z9 112 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 3216 EP 3219 PG 4 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400065 PM 7707554 ER PT J AU WARNER, HR FERNANDES, G WANG, E AF WARNER, HR FERNANDES, G WANG, E TI A UNIFYING HYPOTHESIS TO EXPLAIN THE RETARDATION OF AGING AND TUMORIGENESIS BY CALORIC RESTRICTION SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID DIETARY RESTRICTION; MICE; SENESCENCE; APOPTOSIS; GENE; AGE C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. MCGILL UNIV,JEWISH GEN HOSP,LADY DAVIS INST,BLOOMFIELD CTR RES AGING,MONTREAL,PQ H3T 1E2,CANADA. RP WARNER, HR (reprint author), NIA,BIOL AGING PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 2C231,BETHESDA,MD 20892, USA. FU NIA NIH HHS [R01-AG-03417, AG-10531, AG-09278] NR 25 TC 47 Z9 47 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1995 VL 50 IS 3 BP B107 EP B109 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY603 UT WOS:A1995RY60300001 PM 7743388 ER PT J AU SALERNO, JA GRADY, C MENTIS, M GONZALEZAVILES, A WAGNER, E SCHAPIRO, MB RAPOPORT, SI AF SALERNO, JA GRADY, C MENTIS, M GONZALEZAVILES, A WAGNER, E SCHAPIRO, MB RAPOPORT, SI TI BRAIN METABOLIC FUNCTION IN OLDER MEN WITH CHRONIC ESSENTIAL-HYPERTENSION SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CEREBRAL BLOOD-FLOW; GLUCOSE-UTILIZATION; CEREBROVASCULAR-DISEASE; ALZHEIMERS-DISEASE; INITIAL FINDINGS; RISK-FACTORS; DEMENTIA; RATS; PERFORMANCE; PRESSURE AB Background and Methods. To determine the effects of hypertension on brain function, positron emission tomography (PET) studies using (18F)-2-fluoro-2-deoxy-D-glucose (FDG) were performed on a group of 17 otherwise healthy older hypertensive men (mean age +/- SD = 69 +/- 8 yr) and 25 age- and gender-matched controls. Subjects had medically treated essential hypertension for a minimum of 10 years (range = 10 to 24 yr) with no evidence of end-organ impairment from hypertension by routine clinical screening and by history. All hypertensive and control subjects were determined to be cognitively normal by extensive neuropsychological testing. The hypertensive subjects previously had been reported to have lateral ventricle enlargement and left hemisphere brain atrophy by quantitative MRI. PET data were analyzed using t-tests to look at group differences. Results. The hypertensive subjects were found to have reduced brain glucose utilization in 36/37 regions-of-interest (ROIs). The differences were significant (p < .05) in 10 (27%) of the regions. The thalamic and lenticular nuclei were affected bilaterally. Global values did not significantly differ between groups. Conclusions. Our findings suggest that brain morphologic changes in longstanding, treated hypertension are accompanied by subtle changes in cerebral glucose metabolism. Whereas the changes were most prominent in the subcortical nuclei, there was a strong trend toward hypometabolism throughout the cortex. We speculate that these changes represent early target organ damage in brain regions vulnerable to the effects of chronic hypertension. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 58 TC 20 Z9 20 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1995 VL 50 IS 3 BP M147 EP M154 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY603 UT WOS:A1995RY60300013 PM 7743400 ER PT J AU CAPLAN, LJ LIPMAN, PD AF CAPLAN, LJ LIPMAN, PD TI AGE AND GENDER DIFFERENCES IN THE EFFECTIVENESS OF MAP-LIKE LEARNING-AIDS IN MEMORY FOR ROUTES SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID SEX-DIFFERENCES; ACQUISITION; INFORMATION; KNOWLEDGE AB Young (ages 25-40 yrs) and older (ages 60-75 yrs) adults viewed a series of slides depicting a route through a neighborhood and were tested on their ability to remember the route. Subjects either received no learning aid, a sketch of the route labeled as a ''map,'' or the same aid labeled a ''diagram.'' Aids either did or did not include route landmarks. Relative to younger men, older men's performance was significantly poorer only when they had no learning aid. In contrast, age differences for women were obtained only when the aid had been labeled a ''map.'' The presence of landmarks eliminated age-related decrements in scene memory for men but increased them for women. In addition, results were consistent with the hypothesis that memory for large-scale environments is composed of ''layout'' (i.e., configural) and ''scene'' components. C1 NIMH,BETHESDA,MD 20892. NR 16 TC 9 Z9 9 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1995 VL 50 IS 3 BP P126 EP P133 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA RY949 UT WOS:A1995RY94900001 PM 7767690 ER PT J AU RESNICK, SM TROTMAN, KM KAWAS, C ZONDERMAN, AB AF RESNICK, SM TROTMAN, KM KAWAS, C ZONDERMAN, AB TI AGE-ASSOCIATED CHANGES IN SPECIFIC ERRORS ON THE BENTON VISUAL-RETENTION TEST SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; MEMORY; ATROPHY; BRAIN AB While total errors on the Benton Visual Retention Test (BVRT) are known to increase in normal aging, there is little information on changes for specific error types. We examined the differential increase in seven specific error categories for 2,000 participants in the Baltimore Longitudinal Study of Aging. Cross-sectional analyses indicated that all errors increased with age, but differences between age groups in error profiles suggested relatively greater age effects for distortions, omissions, and rotations. There were also significant gender differences in error profiles, reflecting increased rotation and omission errors in females. Longitudinal analyses of age changes for a subset of 673 participants with three BVRT assessments were consistent with the cross-sectional data and indicated intraindividual increases with age in distortions, omissions, and rotations. While women made more omission errors men showed steeper increases in omission errors with age. These findings suggest that cerebral aging impacts all categories of BVRT errors but has differential effects on particular error types. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21218. RP RESNICK, SM (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 30 TC 11 Z9 12 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1995 VL 50 IS 3 BP P171 EP P178 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA RY949 UT WOS:A1995RY94900006 PM 7767695 ER PT J AU RAPPAPORT, J HANSS, B KOPP, JB COPELAND, TD BRUGGEMAN, LA COFFMAN, TM KLOTMAN, PE AF RAPPAPORT, J HANSS, B KOPP, JB COPELAND, TD BRUGGEMAN, LA COFFMAN, TM KLOTMAN, PE TI TRANSPORT OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES IN KIDNEY - IMPLICATIONS FOR MOLECULAR THERAPY SO KIDNEY INTERNATIONAL LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; ANTISENSE OLIGONUCLEOTIDES; GENE-EXPRESSION; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES; ENDOTHELIAL-CELLS; DNA-BINDING; INHIBITION; STABILITY; INVITRO AB The systemic administration of phosphorothioated antisense oligonucleotides has been demonstrated to be an effective strategy for the control of gene expression. Because previous studies have suggested both hepatic and renal accumulation of systemically administered oligonucleotides, we explored whether the kidney might be a site of free DNA transport. [P-32]-phosphorothioate oligonucleotides (20 mers) were excreted in urine but cleared at only 30% of glomerular filtration rate. Plasma clearance of the label was very rapid (t(1/2) similar to 5 min) but the half life of labeled S-deoxynucleotide excreted in urine was much slower (28 min). Infused oligonucleotide appeared in urine with little degradation. By autoradiography of renal tissue, labeled antisense oligonucleotides appeared within Bowman's capsule and the proximal tubule lumen. DNA was detected in association with brush border membrane and within tubular epithelial cells. Brush border membrane preparations from rat kidney contained oligonucleotide binding proteins as determined by gel mobility shift and UV cross linking assays. Because renal epithelial cells efficiently take up phosphorothioate oligonucleotides without apparent degradation, the kidney appears to be an excellent target for site-directed antisense therapy, but may be a site of antisense toxicity as well. C1 MT SINAI MED CTR,DIV NEPHROL,NEW YORK,NY 10029. NIDR,VIRAL PATHOGENESIS UNIT,BETHESDA,MD. VET ADM MED CTR,DURHAM,NC. DUKE UNIV,DEPT MED,DURHAM,NC. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. OI Kopp, Jeffrey/0000-0001-9052-186X FU PHS HHS [N01-C0-74101] NR 58 TC 108 Z9 109 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1995 VL 47 IS 5 BP 1462 EP 1469 DI 10.1038/ki.1995.205 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA QV942 UT WOS:A1995QV94200029 PM 7637275 ER PT J AU SMITH, MO HEYES, MP LACKNER, AA AF SMITH, MO HEYES, MP LACKNER, AA TI EARLY INTRATHECAL EVENTS IN RHESUS MACAQUES (MACACA-MULATTA) INFECTED WITH PATHOGENIC OR NONPATHOGENIC MOLECULAR CLONES OF SIMIAN IMMUNODEFICIENCY VIRUS SO LABORATORY INVESTIGATION LA English DT Article DE INTRATHECAL SYNTHESIS; AIDS ENCEPHALITIS; QUINOLINIC ACID ID IMMUNE-DEFICIENCY SYNDROME; CENTRAL-NERVOUS-SYSTEM; QUINOLINIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID; HTLV-III; SYNDROME AIDS; PATHOLOGIC FEATURES; VIRAL DETERMINANTS; MACROPHAGE TROPISM; SIV ENCEPHALITIS AB BACKGROUND: Encephalitis is a common and devastating sequela of HIV infection in humans and of simian immunodeficiency virus (SIV) infection in rhesus macaques. We used the SIV-infected rhesus macaque model to study early intrathecal events in the pathogenesis of lentiviral encephalitis. EXPERIMENTAL DESIGN: To examine early events and to compare the neuroinvasiveness and neurovirulence of pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of SIV and the role of host immunity in the early postinfection period, we inoculated groups of rhesus macaques with each of these clones and compared them with a third group of animals inoculated with pathogenic uncloned SIV (SIVmac). We collected paired cerebrospinal fluid and sera before and at intervals after inoculation and determined albumin and IgG concentrations, SIV-specific humoral immune response, and concentrations of quinolinic acid. Two animals from each group were killed and necropsied at 2, 8, 13, and 23 weeks after inoculation. Routine histopathology and semi-quantitative in situ hybridization were performed on tissue from multiple levels of the central nervous system (CNS). RESULTS: SIVmac and SIVmac-239 invaded both the meninges and the CNS parenchyma simultaneously within 2 weeks of inoculation, whereas nonpathogenic SIVmac-1A11 was not neuroinvasive. Gross disruption of the blood-brain barrier was not detected at any time. However, elevated IgG indices and high levels of cerebrospinal fluid quinolinic acid denoted intrathecal immune activation soon after viral neuroinvasion. Virus load in the CNS declined as the immune response peaked but subsequently increased with waning immunity. One macaque that never developed an SIV-specific immune response died with severe SN encephalitis. CONCLUSIONS: Our findings support the following hypotheses of early events in SIV neuropathogenesis: (a) Pathogenic virus invades the CNS within days of i.v. inoculation and elicits an intrathecal immune response, including intrathecal synthesis of IgG and macrophage activation; (b) the immune response initially is associated with a decreased virus load in the CNS; (c) as immunodeficiency develops, virus load in the CNS increases once again; and (d) both virus and host factors are important in determining the course of events. C1 UNIV CALIF DAVIS, CALIF REG PRIMATE RES CTR, DAVIS, CA 95616 USA. NIMH, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR00169]; NINDS NIH HHS [NS30769] NR 89 TC 49 Z9 49 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1995 VL 72 IS 5 BP 547 EP 558 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA QY218 UT WOS:A1995QY21800008 PM 7745949 ER PT J AU KURTZ, A ZIMMER, A AF KURTZ, A ZIMMER, A TI INTERSPECIES FLUORESCENCE IN-SITU HYBRIDIZATION FURTHER DEFINES SYNTENY HOMOLOGY BETWEEN MOUSE CHROMOSOME-11 AND HUMAN-CHROMOSOME-17 SO MAMMALIAN GENOME LA English DT Note ID MAP C1 NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892. RI Zimmer, Andreas/B-8357-2009 NR 7 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1995 VL 6 IS 5 BP 379 EP 380 DI 10.1007/BF00364810 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QX231 UT WOS:A1995QX23100018 PM 7626897 ER PT J AU OHAYON, J CHADWICK, R HERBIN, R AF OHAYON, J CHADWICK, R HERBIN, R TI NONUNIFORM CAVITY PRESSURE AND VENTRICULAR MECHANICS SO MECHANICS RESEARCH COMMUNICATIONS LA English DT Article ID HEART; MODELS; WALL C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. UNIV SAVOIE,MODELISAT MATH & MECAN GM3 GRP,F-73376 LE BOURGET DU LAC,FRANCE. RP OHAYON, J (reprint author), UNIV SAVOIE,ESIGEC,MAT COMPOSITES LAB,EQUIPE STRUCT ANISOTROPES & BIOMECAN,F-73376 LE BOURGET DU LAC,FRANCE. NR 24 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0093-6413 J9 MECH RES COMMUN JI Mech. Res. Commun. PD MAY-JUN PY 1995 VL 22 IS 3 BP 205 EP 219 DI 10.1016/0093-6413(95)00015-J PG 15 WC Mechanics SC Mechanics GA RA804 UT WOS:A1995RA80400001 ER PT J AU RANSON, M TICKLE, C MAHON, KA MACKEM, S AF RANSON, M TICKLE, C MAHON, KA MACKEM, S TI GNOT1, A MEMBER OF A NEW HOMEOBOX GENE SUBFAMILY, IS EXPRESSED IN A DYNAMIC, REGION-SPECIFIC DOMAIN ALONG THE PROXIMODISTAL AXIS OF THE DEVELOPING LIMB SO MECHANISMS OF DEVELOPMENT LA English DT Article DE HOMEOBOX GENES; CHICK EMBRYO; LIMB DEVELOPMENT; PATTERN FORMATION ID CHICK WING DEVELOPMENT; RETINOIC ACID; HOMEOTIC TRANSFORMATIONS; QUANTITATIVE-ANALYSIS; POLARIZING REGION; PATTERN-FORMATION; MURINE; BUD; ORGANIZATION; MORPHOGENESIS AB Limb development endures as an excellent model for pattern formation in vertebrates. We have identified Gnotl as a member of a new homeobox gene subfamily, Gnotl is expressed in a dynamic temporospatial distribution in the developing limb, initially correlating with regions destined to form distal structures and then becoming progressively more restricted to specific regions determined to give rise to wrist and ankle, Micro-surgical alteration of the developmental program of the limb reveals that Gnotl is expressed in a position- and fate-dependent manner, responding both to signals from the apical ridge and the polarizing zone. Furthermore, Gnotl activation by polarizing signals occurs temporally downstream of Herd gene activation, but well before the first appearance of condensations that will give rise to the carpus of the wrist. The features of Gnotl expression suggest a role for this gene in regulating pattern formation during limb development, C1 NCI,NICHD,PATHOL LAB,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. UNIV COLL & MIDDLESEX SCH MED,DEPT ANAT & DEV BIOL,LONDON W1P 6DB,ENGLAND. OI Ranson, Marie/0000-0002-5570-9645 NR 47 TC 16 Z9 16 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 MAY PY 1995 VL 51 IS 1 BP 17 EP 30 DI 10.1016/0925-4773(94)00344-M PG 14 WC Developmental Biology SC Developmental Biology GA RD847 UT WOS:A1995RD84700002 PM 7669689 ER PT J AU RASBAND, WS BRIGHT, DS AF RASBAND, WS BRIGHT, DS TI NIH IMAGE - A PUBLIC DOMAIN IMAGE-PROCESSING PROGRAM FOR THE MACINTOSH SO MICROBEAM ANALYSIS LA English DT Article DE NIH IMAGE; IMAGE PROCESSING; MICROGRAPH ENHANCEMENT AB This paper is a guide to, or a hands-on introduction to, NIH Image, a Macintosh-based, public domain image processing program written by Wayne Rasband, NIH, Bethesda, Maryland. The program and example images are available via anonymous FTP, as described. The reader is introduced to these capabilities of NIH Image: loading image files, contrast enhancement, zoom, pan, drawing, annotation, thresholding, particle counting, image arithmetic, histograms, intensity profiles, Look Up Table modification, image stacks, animation, and 3-D rendering. Various image processing issues are discussed as required. Each image processing step is illustrated for comparison with the results of the individual readers. C1 NIST,DIV SURFACE & MICROANAL SCI,GAITHERSBURG,MD 20899. RP RASBAND, WS (reprint author), NIMH,RES SERV BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 190 Z9 191 U1 1 U2 8 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 1061-3420 J9 MICROBEAM ANAL JI Microbeam Anal. PD MAY-JUN PY 1995 VL 4 IS 3 BP 137 EP 149 PG 13 WC Instruments & Instrumentation; Microscopy; Spectroscopy SC Instruments & Instrumentation; Microscopy; Spectroscopy GA TH084 UT WOS:A1995TH08400004 ER PT J AU DELISLE, AL DONKERSLOOT, JA AF DELISLE, AL DONKERSLOOT, JA TI RELATIONSHIPS AMONG ACTINOMYCES-NAESLUNDII (A-VISCOSUS) BACTERIOPHAGES ISOLATED FROM SEWAGE AND THE ORAL CAVITY SO MICROBIAL ECOLOGY IN HEALTH AND DISEASE LA English DT Article DE ACTINOMYCES; BACTERIOPHAGES; ORAL PHAGES; DENTAL PLAQUE ID COAGGREGATION; FIMBRIAE; BACTERIA; GENE AB Several lytic phages of Actinomyces naeslundii genospecies 2 (formerly A. viscosus) have been isolated from sewage and from dental plaque. To define the relationships between these phages and ultimately to assess their role in the ecology of the human oral cavity, 13 phages isolated from these two environments were purified and their biochemical properties compared. Five small, short-tailed phages, isolated from sewage over the course of several years (Av-1, Av-2, Av-3, 1281, and BF307) were morphologically indistinguishable from each other and from five phages recovered more recently from human dental plaque (CT1, CT2, CT3, CT6 and CT7). The small phages (all morphotype C1) contained double-stranded linear DNA, 18 kb in size. In contrast, three phages from dental plaque (CT4, CT5 and CT8) possessed longer tails and much larger head structures (morphotype B1). Two of the larger phages (CT4 and CT5) contained DNA genomes estimated to be 80 kb in size, whereas large phage CT8 contained DNA of approximately 50 kb. Restriction endonuclease analysis revealed extensive differences between the large and small phages but the latter group showed similar, and in several cases identical, fragment patterns. These results indicate the existence of at least three distinct types of lytic bacteriophage active against oral Actinomyces spp. The similarities between the sewage and small dental plaque isolates indicate a high degree of relatedness and suggest that the sewage phages probably originated from the oral cavity. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP DELISLE, AL (reprint author), UNIV MARYLAND,SCH DENT,DEPT MICROBIOL,BALTIMORE,MD 21201, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0891-060X J9 MICROB ECOL HEALTH D JI Microb. Ecol. Health Dis. PD MAY-JUN PY 1995 VL 8 IS 3 BP 121 EP 127 PG 7 WC Ecology; Immunology; Microbiology SC Environmental Sciences & Ecology; Immunology; Microbiology GA RP356 UT WOS:A1995RP35600006 ER PT J AU HAYES, HM TARONE, RE CASEY, HW AF HAYES, HM TARONE, RE CASEY, HW TI A COHORT STUDY OF THE EFFECTS OF VIETNAM SERVICE ON TESTICULAR PATHOLOGY OF US MILITARY WORKING DOGS SO MILITARY MEDICINE LA English DT Article AB Using histopathologic diagnoses made on necropsy material from 3,024 military working dogs (MWDs) who died from 1968 to 1973, we analyzed the effect of military service in the Republic of Vietnam on testicular pathology. Among 1,048 MWDs that died in Vietnam and had no reported developmental risk factors for testicular disease, significant excesses of testicular hemorrhage, epididymitis/orchitis, sperm granuloma, testicular degeneration, and seminoma were evident. Among 126 MWDs with prior Vietnam service who died at other duty stations outside Vietnam from 1968 to 1973, significant excesses of testicular degeneration and seminoma were likewise evident. Among 136 MWDs with prior Vietnam service that later died from 1974 to 1980, seminoma continued to be diagnosed in significant excess. In each instance, the odds ratio for the association between Vietnam service and seminoma was 2.0 or greater. Analysis of ever service by Corps Tactical Zones showed significant excesses of seminoma with each Corps area of service compared to Vietnam-era MWDs, but risk was highest in I Corps, particularly at Da Nang Port and Da Nang Air Base. This finding with respect to I Corps is consistent with certain human studies in Vietnam veterans and points to the need for further investigation of possible environmental exposures, particularly those associated to a greater extent with service in I Corps. RP HAYES, HM (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN ROOM 443,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 2 U2 5 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 1995 VL 160 IS 5 BP 248 EP 255 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA RE457 UT WOS:A1995RE45700012 PM 7659215 ER PT J AU MASISON, DC BLANC, A RIBAS, JC CARROLL, K SONENBERG, N WICKNER, RB AF MASISON, DC BLANC, A RIBAS, JC CARROLL, K SONENBERG, N WICKNER, RB TI DECOYING THE CAP(-) MESSENGER-RNA DEGRADATION SYSTEM BY A DOUBLE-STRANDED-RNA VIRUS AND POLY(A)- MESSENGER-RNA SURVEILLANCE BY A YEAST ANTIVIRAL SYSTEM SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EUKARYOTIC MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; L-A; SUPERKILLER MUTATIONS; BINDING-PROTEIN; CYTO-PATHOLOGY; INTERNAL ENTRY; COAT PROTEIN; 5' ENDS; EXPRESSION AB The major coat protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae covalently binds m(7)GMP from 5' capped mRNAs in vitro. We show that this cap binding also occurs in vivo and that, while this activity is required for expression of viral information (killer toxin mRNA level and toxin production) in a wild-type strain, this requirement is suppressed by deletion of SKI1/XRN1/SEP1. We propose that the virus creates decapped cellular mRNAs to decoy the 5' --> 3' exoribonuclease specific for cap(-) RNA encoded by XRN1. The SKI2 antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S RNA replicon, apparently by specifically blocking translation of viral RNA. We show that SKI2, SKI3, and SKI8 inhibit translation of electroporated luciferase and beta-glucuronidase mRNAs in vivo, but only if they lack the 3' poly(A) structure. Thus, L-A decoys the SKI1/XRN1/SEP1 exonuclease directed at 5' uncapped ends, but translation of the L-A poly(A)(-) mRNA is repressed by Ski2,3,8p. The SKI2-SKI3-SKI8 system is more effective against cap(+) poly(A)(-) mRNA, suggesting a (nonessential) role in blocking translation of fragmented cellular mRNAs. C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3G 1Y6,CANADA. RI Ribas, Juan/C-9864-2015 OI Ribas, Juan/0000-0001-6430-0895 NR 64 TC 92 Z9 99 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 MAY PY 1995 VL 15 IS 5 BP 2763 EP 2771 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500047 PM 7739557 ER PT J AU OHTAKE, Y WICKNER, RB AF OHTAKE, Y WICKNER, RB TI YEAST VIRUS PROPAGATION DEPENDS CRITICALLY ON FREE 60S RIBOSOMAL-SUBUNIT CONCENTRATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; SACCHAROMYCES-CEREVISIAE; L-A; GAG-POL; N-ACETYLTRANSFERASE; TRANSLATION INITIATION; TOPOISOMERASE ACTIVITY; SUPERKILLER MUTATIONS; MESSENGER-RNA; PROTEIN AB Over 30 MAK (maintenance of killer) genes are necessary for propagation of the killer toxin-encoding M(1) satellite double-stranded RNA of the L-A virus. Sequence analysis revealed that MAK7 is RPL4A, one of the two genes encoding ribosomal protein L4 of the 60S subunit. We further found that mutants with mutations in 18 MAK genes (including mak1 [top1], mak7 [rpl4A], mak8 [rpl3], mak11, and mak16) had decreased free 60S subunits. Mutants with another three mak mutations had half-mer polysomes, indicative of poor association of 60S and 40S subunits. The rest of the mak mutants, including the mak3 (N-acetyltransferase) mutant, showed a normal profile. The free 60S subunits, L-A copy number, and the amount of L-A coat protein in the mak1, mak7, mak11, and mak16 mutants were raised to the normal level by the respective normal single-copy gene. Our data suggest that most mak mutations affect M(1) propagation by their effects on the supply of proteins from the GA virus and that the translation of the non-poly(A) L-A mRNA depends critically on the amount of free 60S ribosomal subunits, probably because 60S association with the 40S subunit waiting at the initiator AUG is facilitated by the 3' poly(A). C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. NR 61 TC 74 Z9 77 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2772 EP 2781 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500048 PM 7739558 ER PT J AU WATTS, RG BENARI, ET BERNSTEIN, LR BIRRER, MJ WINTERSTEIN, D WENDEL, E COLBURN, NH AF WATTS, RG BENARI, ET BERNSTEIN, LR BIRRER, MJ WINTERSTEIN, D WENDEL, E COLBURN, NH TI C-JUN AND MULTISTAGE CARCINOGENESIS - ASSOCIATION OF OVEREXPRESSION OF INTRODUCED C-JUN WITH PROGRESSION TOWARD A NEOPLASTIC END-POINT IN MOUSE JB6 CELLS SENSITIVE TO TUMOR PROMOTER-INDUCED TRANSFORMATION SO MOLECULAR CARCINOGENESIS LA English DT Article DE TRANSFORMATION; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; AP-1 ID CHICKEN-EMBRYO FIBROBLASTS; CYCLOSPORINE-A; NUCLEAR FACTOR; FOS JUN; EXPRESSION; RESISTANT; GENE; FAMILY; SEQUENCES; PHENOTYPE AB Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (ECF) induce neoplastic transformation, elevated c-jun protein expression, and activator protein-1 (AP-l)-dependent gene expression in JB6 mouse epidermal cells sensitive to tumor promoters (clone 415a Pc cells). In contrast, JB6 cells resistant to tumor promoter-induced transformation (clone 307b P- cells) exhibit a greatly reduced IPA or EGF inducible c-jun expression and AP-1 activity. We have recently shown that induced AP-1 is necessary for tumor promoter-induced transformation of Pc cells because introduction of a dominant negative c-jun mutant into Pc cells inhibits both AP-1 dependent transactivation and the transformation response to tumor promoter. The intent of the investigation presented here was to test the hypothesis that elevation of AP-1 activity is sufficient to cause progression to the Pc phenotype in P- cells or to the transformed phenotype in Pc cells. Clonally derived Pc and P- recipient cells transfected with a human c-jun expression construct and overexpressing c-jun protein were tested for progression by assaying for constitutive or inducible anchorage independent phenotype and nude-mouse tumorigenicity. Overexpression of c-jun did not produce progression in P- cells but did increase the probability of progression in Pc cells (two of five transfectant cell lines progressed to the tumor phenotype). In addition, c-jun overexpression did not increase AP-1 activity in any of the P-/-c-jun transfectants or in the two of five P+/-c-jun transfectants that acquired the transformed phenotype. The P+/-c-jun transfectants that showed elevated AP-1 activity did not progress to the tumor phenotype, demonstrating that an increase in AP-1 activity is insufficient for this progression. Since Pc-to-tumor phenotype progression occurred in cells overexpressing c-jun but not AP-1, we propose that P+-to-transformed phenotype progression is c-jun dependent and AP-1 independent. (C) 1995 Wiley-Liss, Inc. C1 NCI,MOLEC MECHANISM SECT,ROCKVILLE,MD. PRI DYNCORP,FREDERICK,MD. RP WATTS, RG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 37 TC 31 Z9 31 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1995 VL 13 IS 1 BP 27 EP 36 DI 10.1002/mc.2940130106 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA RB033 UT WOS:A1995RB03300005 PM 7766308 ER PT J AU SILVERMAN, JA HILL, BA AF SILVERMAN, JA HILL, BA TI CHARACTERIZATION OF THE BASAL AND CARCINOGEN REGULATORY ELEMENTS OF THE RAT MDR1B PROMOTER SO MOLECULAR CARCINOGENESIS LA English DT Article DE AFLATOXIN B-1; N-ACETOXY-2-ACETYLAMINOFLUORENE; METHYL METHANESULFONATE; TRANSCRIPTION ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN GENE; MAMMALIAN-CELLS; TRANSCRIPTIONAL REPRESSION; HEPATOCYTE CULTURES; MESSENGER-RNA; HEAT-SHOCK; EXPRESSION; FAMILY; SEQUENCE AB In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B-1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. Nuclear run-on experiments indicated that the higher steady-state levels of mdr1b mRNA were due to an increase in transcription. The 5'-flanking region of the mdr1b gene was isolated, sequenced, and functionally characterized in transient and stable transfection assays. A single transcription start site was identified for this gene; no alternate start sites were used after induction with aflatoxin B-1. Deletion analysis of this promoter demonstrated that the sequence between nt -214 and -178 was critical for basal promoter activity. This region did not contain any consensus-binding sites for previously identified transcription factors. A negative regulatory region was also identified between nt -940 and -250. No specific carcinogen-responsive element was identified; the xenobiotic response required a large part of the promoter. These data suggest that the carcinogen induction of mdr1b expression is mediated through sequences that overlap or that are identical to the basal promoter element. (C) 7995 Wiley-Liss, Inc. RP SILVERMAN, JA (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C25,BETHESDA,MD 20892, USA. NR 53 TC 34 Z9 34 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1995 VL 13 IS 1 BP 50 EP 59 DI 10.1002/mc.2940130109 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA RB033 UT WOS:A1995RB03300008 PM 7766310 ER PT J AU SHIMURA, H SHIMURA, Y OHMORI, M IKUYAMA, S KOHN, LD AF SHIMURA, H SHIMURA, Y OHMORI, M IKUYAMA, S KOHN, LD TI SINGLE-STRAND DNA-BINDING PROTEINS AND THYROID TRANSCRIPTION FACTOR-I CONJOINTLY REGULATE THYROTROPIN RECEPTOR GENE-EXPRESSION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; TISSUE-SPECIFIC EXPRESSION; INDUCED UP-REGULATION; GROWTH FACTOR-I; THYROGLOBULIN PROMOTER; DOWN-REGULATION; RESPONSE ELEMENT; NUCLEAR-PROTEIN; MESSENGER-RNA; CELLS AB An element, -186 to -176 base pairs (bp), in the minimal TSH receptor (TSHR) promoter binds thyroid transcription factor-1 (TTF-1) and is important for both constitutive expression and TSH/cAMP-induced negative autoregulation of the TSHR in thyroid cells. An element on the noncoding strand of the TSHR, contiguous with the 5'-end of the TTF-1 element, has single strand binding activity. It is distinct from the TTF-1 site, as evidenced by competition experiments using gel shift assays; but the association of the two elements is not random. Thus, the single strand binding protein (SSBP) element also exists contiguous to the 5'-end of an upstream TTF-1 site, -881 to -866 bp; mutation of two conserved nucleotides in each SSBP element results in the loss of SSBP binding and cross-competition. Transfection experiments indicate that full, constitutive TSHR gene expression in FRTL-5 thyroid cells requires the binding of both SSBPs and TTF-1, since mutation of either element halves thyroid-specific promoter activity, whereas mutation of both decreases promoter activity to values near those of a control vector. Transfection experiments with rat liver cells support their independent activities and show that the SSBP site contributes to TSHR gene expression in non-thyroid tissue. The SSBPs function conjointly with TTF-1 in thyroid-specific, TSH/cAMP-induced negative autoregulation of the TSHR. Thus, TSH or forskolin-treated FRTL-5 cells coordinately decrease TSHR RNA levels and TSHR DNA binding to both the SSBPs and TTF-1; also the maximal TSH/cAMP-induced decrease in gene expression requires both elements. The TSH-induced effect in each case is inhibited by cycloheximide; the TSH-induced decrease in SSBP/DNA complex formation requires the presence of insulin or calf serum, exactly as does TSH-induced down-regulation of TSHR RNA levels. In sum, full, constitutive expression of the TSHR in thyroid cells requires TTF-1 and the SSBPs to bind separate, contiguous elements on the TSHR promoter. TSH/cAMP decreases the binding of each factor to its respective site, thereby decreasing TSHR gene expression. The role of the SSBP and TTF-1 sites in constitutive TSHR expression and in TSH/cAMP-induced negative regulation of the TSHR is, therefore, additive and independent. C1 NIDDKD, DEPT BIOCHEM METAB, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NR 52 TC 38 Z9 38 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1995 VL 9 IS 5 BP 527 EP 539 DI 10.1210/me.9.5.527 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW546 UT WOS:A1995QW54600001 PM 7565801 ER PT J AU KESSLER, PM VASAVADA, SP RACKLEY, RR STACKHOUSE, T DUH, FM LATIF, F LERMAN, MI ZBAR, B WILLIAMS, BRG AF KESSLER, PM VASAVADA, SP RACKLEY, RR STACKHOUSE, T DUH, FM LATIF, F LERMAN, MI ZBAR, B WILLIAMS, BRG TI EXPRESSION OF THE VONHIPPEL-LINDAU TUMOR-SUPPRESSOR GENE, VHL, IN HUMAN FETAL KIDNEY AND DURING MOUSE EMBRYOGENESIS SO MOLECULAR MEDICINE LA English DT Article ID RENAL-CELL CARCINOMA; DISEASE AB Background: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome that has a dominant inherited pattern which predisposes affected individuals to a variety of tumors. The most frequent tumors are hemangioblastomas of the central nervous system and retina, renal cell carcinoma (RCC), and pheochromocytoma. The recent identification and characterization of the VHL gene on human chromosome 3p and mutational analyses confirms the VHL gene functions as a classical tumor suppressor. Not only are mutations in this gene responsible for the VHL syndrome, but mutations are also very frequent in sporadic RCC. Materials and Methods: VHL expression in human kidney and during embryogenesis, was analyzed by in situ mRNA hybridization with S-35-labeled antisense VHL probes, derived from human and mouse cDNAs, on cryosections of human fetal kidney and paraffin sections of murine embryos. Results: Ln human fetal kidney, there was enhanced expression of VHL within the epithelial lining of the proximal tubules. During embryogenesis, VHL expression was ubiquitous in all three germ cell layers and their derivatives. Expression occurred in the cerebral cortex, midbrain, cerebellum, retina, spinal cord, and postganglionic cell bodies. All organs of the thoracic and abdominal cavities expressed VHL, but enhanced expression was most apparent in the epithelial components of the lung, kidney, and eye. Conclusions: In human fetal kidney, the enhanced epithelial expression of the VHL gene is consistent with the role of this gene in RCC. There is widespread expression of the VHL gene during embryogenesis, but this is pronounced in areas associated with VHL phenotypes. These findings provide a histological framework for investigating the physiological role of the VHL gene and as basis for further mutational analysis. C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,RES INST,DEPT UROL,CLEVELAND,OH 44195. NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,IMMUNOBIOL LAB,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Williams, Bryan/A-5021-2009 OI Williams, Bryan/0000-0002-4969-1151 NR 15 TC 42 Z9 44 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1995 VL 1 IS 4 BP 457 EP 466 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QZ097 UT WOS:A1995QZ09700014 PM 8521303 ER PT J AU CIEPLAK, W MESSER, RJ KONKEL, ME GRANT, CCR AF CIEPLAK, W MESSER, RJ KONKEL, ME GRANT, CCR TI ROLE OF A POTENTIAL ENDOPLASMIC-RETICULUM RETENTION SEQUENCE (RDEL) AND THE GOLGI-COMPLEX IN THE CYTOTONIC ACTIVITY OF ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN SO MOLECULAR MICROBIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; NUCLEOTIDE-BINDING-PROTEINS; BREFELDIN-A; CHOLERA-TOXIN; PSEUDOMONAS EXOTOXIN; ORGANELLE STRUCTURE; ADENYLATE-CYCLASE; MEMBRANE-PROTEIN; VIBRIO-CHOLERAE; CULTURED-CELLS AB Recent experimental evidence indicates that Escherichia coli heat-labile enterotoxin and the closely related cholera toxin gain access to intracellular target substrates through a brefeldin A-sensitive pathway that may involve retrograde transport through the Golgi-endoplasmic reticulum network. The A subunits of both toxins possess a carboxy-terminal tetrapeptide sequence (KDEL in cholera toxin and RDEL in the heat-labile enterotoxins) that is known to mediate the retention of eukaryotic proteins in the endoplasmic reticulum. To investigate the potential role of the RDEL sequence in the toxic activity of the heat-labile enterotoxin we constructed mutant analogues of the toxin containing single substitutions (RDGL and RDEV) or a reversed sequence (LEDR). The single substitutions had little effect on Chinese hamster ovary cell elongation or the ability to stimulate cAMP accumulation in Caco-2 cells. Reversal of the sequence reduced the ability of the toxin to increase cAMP levels in Caco-5 cells by approximately 60% and decreased the ability to elicit elongation of Chinese hamster ovary cells. The effects of the heat-labile enterotoxin were not diminished in a mutant Chinese hamster ovary cell line (V.24.1) that belongs to the End4 complementation group and possesses a temperature-sensitive block in secretion that correlates directly with the disappearance of the Golgi stacks. Collectively, these findings suggest that the brefeldin A-sensitive process involved in intoxication by the heat-labile enterotoxin does not involve RDEL-dependent retrograde transport of the A subunit through the Golgi-endoplasmic reticulum complex. The results are more consistent with a model of internalization involving translocation of the A subunit from an endosomal or a trans-Golgi network compartment. RP CIEPLAK, W (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 62 TC 34 Z9 34 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 MAY PY 1995 VL 16 IS 4 BP 789 EP 800 DI 10.1111/j.1365-2958.1995.tb02440.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA RF961 UT WOS:A1995RF96100018 PM 7476173 ER PT J AU SCHAAD, NC VANECEK, J RODRIGUEZ, IR KLEIN, DC HOLTZCLAW, L RUSSELL, JT AF SCHAAD, NC VANECEK, J RODRIGUEZ, IR KLEIN, DC HOLTZCLAW, L RUSSELL, JT TI VASOACTIVE-INTESTINAL-PEPTIDE ELEVATES PINEALOCYTE INTRACELLULAR CALCIUM CONCENTRATIONS BY ENHANCING INFLUX - EVIDENCE FOR INVOLVEMENT OF A CYCLIC GMP-DEPENDENT MECHANISM SO MOLECULAR PHARMACOLOGY LA English DT Article ID SEROTONIN-N-ACETYLTRANSFERASE; CYTOSOLIC GUANYLATE-CYCLASE; RAT PINEALOCYTES; ALPHA-1-ADRENERGIC POTENTIATION; ADRENERGIC-STIMULATION; FUNCTIONAL EXPRESSION; ADENYLATE-CYCLASE; GATED CHANNEL; CELLS; POLYPEPTIDE AB Vasoactive intestinal peptide (VIP) receptor density is high in the pineal gland, which receives VIP innervation and responds to VIP with a relatively small increase in cAMP and cGMP levels. In the present study, we show that VIP (5-200 nm) treatment increased the intracellular calcium concentration ([Ca2+](i)) in 64% of isolated individual pinealocytes; in comparison, norepinephrine (NE) elevated [Ca2+], in 93% of the cells and produced more robust responses. Analysis of the role of second messengers indicated that [Ca2+](i) was strongly elevated by cGMP analogs, but not by cAMP analogs. The nitric oxide-releasing agent S-nitro-N-acetylpenicillamine and 2,2-diethyl-1-nitroxyhydrazine also elevated [Ca2+](i). Investigation of the mechanisms revealed that responses to VIP or 8-bromo-cGMP involved Ca2+ influx, as did the plateau component of the response to NE; the large rapid component of the response to NE, however, appeared to reflect release from intracellular stores. Pharmacological studies indicated that the VIP-induced Ca2+ influx was mediated by a retinal rod-type cyclic nucleotide-gated cation channel, expression of which was confirmed by reverse transcription-polymerase chain reaction analysis. These observations indicate that fundamentally different mechanisms generate the responses to NE and VIP. The dominant effect of VIP causing transient elevation of [Ca2+](i) appears to be through cGMP gating a I-cis-diltiazem-sensitive rod-type cyclic nucleotide-gated cation channel. In contrast, the dominant effect of NE on [Ca2+](i) is due to enhanced Ca2+ release from intracellular stores; the plateau component is due to influx through a I-cis-diltiazem-insensitive channel. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,NEURONAL SECRETORY SYST SECT,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. ACAD SCI CZECH REPUBL,INST PHYSIOL,PRAGUE,CZECH REPUBLIC. NR 44 TC 48 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1995 VL 47 IS 5 BP 923 EP 933 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX979 UT WOS:A1995QX97900006 PM 7538196 ER PT J AU VAUGHAN, RA AF VAUGHAN, RA TI PHOTOAFFINITY-LABELED LIGAND-BINDING DOMAINS ON DOPAMINE TRANSPORTERS IDENTIFIED BY PEPTIDE-MAPPING SO MOLECULAR PHARMACOLOGY LA English DT Article ID NUCLEUS-ACCUMBENS; COCAINE; CLONING; GLYCOSYLATION; EXPRESSION; STRIATUM; COMPLEX; PROTEIN; SITES AB Binding domains on rat dopamine transporters for cocaine and 1-(2-diphenylmethoxy)ethyl-4-(3-phenylpropyl)piperazine compounds were identified using controlled proteolysis of photoaffinity-labeled protein and epitope-specific immunoprecipitation of the labeled fragments. Rat dopamine transporters were photoaffinity labeled with 1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-azido-3-[I-125] iodophenyl)ethyl]piperazine ([I-125]DEEP) [a1-(2-diphenylmethoxy)ethyl-4-(3-phenylpropyl)piperazine analog] or 3 beta-(rho-chlorophenyl)tropane-2 beta-carboxylic acid, 4'-azido-3'-[I-125] iodophenylethyl ester ([I-125]RTI 82) (a cocaine analog) and were gel purified to remove contaminating radioactivity. The resulting samples were treated with V8 protease or trypsin and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The peptide maps generated with each enzyme were different for each of the ligands, suggesting that the ligands were incorporated into different regions of the protein. Identical peptide maps were generated from striatum- and nucleus accumbens-derived transporters, indicating that these polypeptides are highly similar in primary sequence. The proteolytic fragments generated by V8 protease were localized to specific domains of the protein using antipeptide antibodies corresponding to five different regions of the transporter. Fragments of 10 and 7 kDa from [I-125]DEEP-labeled transporters were specifically immunoprecipitated with an antibody generated against amino acids 42-59 (near the first putative transmembrane domain), whereas a 34-kDa fragment from [I-125]RTI 82-labeled transporters was precipitated with three different sera corresponding to regions in the carboxyl-terminal two thirds of the protein. None of the V8 fragments smaller than 45 kDa, containing either photolabel, was altered in molecular mass by N-deglycosylation. The results indicate that photoincorporation of [I-125]DEEP occurs in the amino half of the dopamine transporter, near the first two transmembrane helices, whereas [I-125]RTI 82 labels the carboxyl-terminal region of the protein, between transmembrane domains 4 and 12. RP VAUGHAN, RA (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 34 TC 61 Z9 61 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1995 VL 47 IS 5 BP 956 EP 964 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX979 UT WOS:A1995QX97900010 PM 7746282 ER PT J AU BAI, RL TAYLOR, GF SCHMIDT, JM WILLIAMS, MD KEPLER, JA PETTIT, GR HAMEL, E AF BAI, RL TAYLOR, GF SCHMIDT, JM WILLIAMS, MD KEPLER, JA PETTIT, GR HAMEL, E TI INTERACTION OF DOLASTATIN-10 WITH TUBULIN - INDUCTION OF AGGREGATION AND BINDING AND DISSOCIATION REACTIONS SO MOLECULAR PHARMACOLOGY LA English DT Article ID BOVINE BRAIN TUBULIN; MACROCYCLIC LACTONE ANTIBIOTICS; PHOMOPSIN-A; ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS; MAYTANSINE-BINDING; NATURAL-PRODUCTS; RHIZOXIN BINDING; VINCA ALKALOIDS; HALICHONDRIN-B AB We have prepared [H-3]dolastatin 10 and examined its interactions with tubulin. Binding kinetics appeared to be biphasic, with a rapid initial reaction that could not be accurately measured, followed by a slower second reaction. Bound drug was stable in centrifugal gel filtration, column gel filtration, and high performance liquid chromatography gel filtration, but the bound drug could be displaced by an active isomer of dolastatin 10. Scatchard analysis of binding data was consistent with two classes of binding sites. However, dolastatin 10 induced an aggregation reaction upon binding to tubulin, complicating analysis of the data, and incorporation of [H-3]dolastatin 10 into large aggregates was readily demonstrated. The chromatographic properties of the smallest radiolabeled species that could be documented were most consistent with a complex consisting of two molecules of alpha/beta-tubulin dimer and two molecules of [H-3]dolastatin 10. The coexistence of an aggregation reaction with a binding reaction at a single site probably underlies the biphasic binding kinetics and the biphasic Scatchard plot. Of peptides that strongly inhibit tubulin polymerization (dolastatin 10, dolastatin 10 isomers, segments, and analogs, dolastatin 15, and phomopsin A), only those previously shown to be strong inhibitors of vinblastine binding and nucleotide exchange also strongly inhibited [3H]dolastatin 10 binding and induced tubulin aggregation (dolastatin 10 itself, two chiral isomers of dolastatin 10, and phomopsin A). The morphology of dolastatin 10-induced aggregates was compared with that of vinblastine-induced aggregates under a variety of reaction conditions. With both drugs the aggregates had a more organized appearance when microtubule-associated proteins were included in the reaction. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. NR 36 TC 56 Z9 58 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1995 VL 47 IS 5 BP 965 EP 976 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX979 UT WOS:A1995QX97900011 PM 7746283 ER PT J AU KNECHT, KT ADACHI, Y BRADFORD, BU IIMURO, Y KADIISKA, M QUNHUI, X THURMAN, RG AF KNECHT, KT ADACHI, Y BRADFORD, BU IIMURO, Y KADIISKA, M QUNHUI, X THURMAN, RG TI FREE-RADICAL ADDUCTS IN THE BILE OF RATS TREATED CHRONICALLY WITH INTRAGASTRIC ALCOHOL - INHIBITION BY DESTRUCTION OF KUPFFER CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID CARBON-TETRACHLORIDE; SWIFT INCREASE; LIPID-PEROXIDATION; LIVER MACROPHAGES; OXYGEN RADICALS; ETHANOL; METABOLISM; INVIVO; HEPATOTOXICITY; DEHYDROGENASE AB Free radical products have previously been detected in rodents after chronic feeding with an ethanol-containing, high-fat diet. The significance of reactive free radical formation in ethanol-induced hepatotoxicity has been difficult to assess because most rodent models exhibit only fatty liver. However, serious hepatic damage resembling clinical alcoholic liver injury (e.g., steatosis, inflammation, and necrosis) occurs in rats after continuous intragastric administration of an ethanol-containing, high-fat diet developed by Tsukamoto and French. Accordingly, rats treated with ethanol for at least 2 weeks using this protocol were administered the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, and bile samples were collected. A six-line radical adduct spectrum was detected in the bile of ethanol-treated rats. A similar spectrum of lower intensity was detected with rats fed a high-fat diet without ethanol, but little or no radical adduct signal was detected with chow-fed animals. For both treatment groups, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone and extra ethanol were given acutely. Destruction of Kupffer cells by chronic treatment with GdCl3 decreased by about 50% the radical adduct formation in rats fed the ethanol-containing, high-fat diet. This radical species was largely ethanol derived, because addition of [C-13]ethanol produced a 12-line spectrum, indicating the formation of alpha-hydroxyethyl radical. Ethanol treatment also caused hypoxia (detected on the liver surface in vivo with oxygen electrodes), which was reflected in a dose-dependent decrease in oxygen tension with ethanol. The effect was blocked by GdCl3. Hepatic damage detected by histology was prevalent in ethanol-treated rats but only mild fatty liver was observed in high-fat diet-fed controls. GdCl3 treatment eliminated hepatic damage due to high-fat and ethanol diets, acid when all groups were compared a significant correlation between liver injury and radical adduct signal was observed. Thus, free radical formation in ethanol-treated rats has been detected for the first time in a model that exhibits injury characteristic of human alcoholic injury, and signal intensity correlates with hepatotoxicity. Moreover, the decrease in both free radical formation and hepatic damage produced by GdCl3 implicates Kupffer cells in the development of alcoholic liver injury. This important pathophysiological process may involve direct production of reactive oxygen species or indirect actions of mediators on parenchymal cells. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. OHIO NO UNIV,COLL PHARM,ADA,OH 45810. NIEHS,RES TRIANGLE PK,NC 27709. FU NIAAA NIH HHS [AA03624, AA09156] NR 34 TC 100 Z9 103 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1995 VL 47 IS 5 BP 1028 EP 1034 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX979 UT WOS:A1995QX97900018 PM 7746269 ER PT J AU ODONOVAN, MR FREEMANTLE, MR HULL, G BELL, DA ARLETT, CF COLE, J AF ODONOVAN, MR FREEMANTLE, MR HULL, G BELL, DA ARLETT, CF COLE, J TI EXTENDED-TERM CULTURES OF HUMAN T-LYMPHOCYTES - A PRACTICAL ALTERNATIVE TO PRIMARY HUMAN-LYMPHOCYTES FOR USE IN GENOTOXICITY TESTING SO MUTAGENESIS LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; RESISTANT MUTANT FREQUENCY; INDUCED CHROMOSOME-DAMAGE; DNA-REPAIR; INTERINDIVIDUAL VARIATION; CARCINOGEN-METABOLISM; CANCER SUSCEPTIBILITY; BLADDER-CANCER; CLONING ASSAY; CELL GROWTH AB A simplified method, using recombinant interleukin-2, foetal bovine serum and freeze-killed feeder cells, has been developed for the mass culture of T-lymphocytes derived from human peripheral blood. In this protocol, bulk cultures can be cryopreserved similar to 8 days after initiation, and subsequent mass cultures generated a further week after recovery. At the end of this period, the lymphocytes have maintained a normal karyotype and cultures from different donors are very similar in terms of rate of cell division and expression of key antigenic markers, Background micronucleus frequencies and dose-responses for micronucleus induction by a reference clastogen, hycanthone, were also very similar in all the cultures examined. Such extended-term T-lymphocyte cultures are potentially valuable in genotoxicity testing, providing cells with the normal human karyotype which can be characterised and handled with the practical convenience of established rodent cell lines. C1 UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DEPT IMMUNOL,NOTTINGHAM NG7 2UH,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. UNIV SUSSEX,MRC,CELL MUTAT UNIT,BRIGHTON BN1 9RR,E SUSSEX,ENGLAND. RP ODONOVAN, MR (reprint author), BOOTS PHARMACEUT,RES DEPT,NOTTINGHAM,ENGLAND. NR 61 TC 32 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAY PY 1995 VL 10 IS 3 BP 189 EP 201 DI 10.1093/mutage/10.3.189 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA RB038 UT WOS:A1995RB03800007 PM 7666770 ER PT J AU DESERRES, FJ MALLING, HV ONG, TM AF DESERRES, FJ MALLING, HV ONG, TM TI COMPARISON OF THE MUTAGENICITY AND MUTAGEN SPECIFICITY OF ETHYLENIMINE WITH TRIETHYLENEMELAMINE IN THE AD-3 REGION OF HETEROKARYON-12 OF NEUROSPORA-CRASSA SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE HETEROKARYON 12; GENE POINT MUTATION; MULTIPLE-LOCUS MUTATION; MULITLOCUS DELETION MUTATION; AD-3 REGION; AD-3A LOCUS; AD-3B LOCUS; RECESSIVE LETHAL MUTATION; TRIETHYLENEMELAMINE; ETHYLENIMINE; AD-3B AD-3A RATIO ID MULTIPLE-LOCUS MUTATIONS; UNEXPECTEDLY HIGH-FREQUENCY; 2-COMPONENT HETEROKARYONS; MULTILOCUS DELETION; IRREPARABLE MUTANTS; GENOTYPE AD-3A; SPECTRA AB Studies have been performed to compare the mutagenicity and mutagenic specificity of the trifunctional alkylating agent, triethylenemelamine (TEM), and a closely related monofunctional agent, ethylenimine (EI), in the adenine-3 (ad-3) region of a 2-component heterokaryon (H-12) of Neurospora crassa. The primary objective of our studies was to characterize the genetic damage produced by each agent with regard to (1) mutagenic potency, and (2) the spectrum of specific-locus mutations induced in a lower eukaryotic organism. As in higher eukaryotes, specific-locus mutations in the ad-3 region of H-12 result from gene/point mutations, multilocus deletion mutations, and multiple-locus mutations. Specific-locus mutations resulting from gene/point mutation and multilocus deletion mutation can be detected in higher eukaryotes, but multiple-locus mutations can be detected only with difficultly or not at all. Our experiments with the ad-3 forward-mutation assay have demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) and EI is a moderate mutagen (maximum forward-mutation frequency between 10 and 100 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Classical genetic tests were used to identify the different genotypic classes and subclasses among the EI- and TEM-induced ad-3 mutations from each experiment. The overall data base demonstrates that both EI- and TEM-induced ad-3 mutations result predominantly from gene/point mutations at the ad-3A and ad-3B loci (97.3% and 95.5%, respectively), and infrequently from multilocus deletion mutations (2.7% and 4.5%, respectively). Heterokaryon tests for allelic complementation on TEM- and EI-induced ad-3B mutations, however, have revealed a difference between the percentages showing allelic complementation (63.1% and 40.9%, respectively). Based on the specific revertibility of complementing and noncomplementing ad-3B mutations induced by other agents, this difference in the percentages of ad-3B mutations showing allelic complementation results from a difference between the spectrum of genetic alterations at the molecular level. In addition, comparison of the ratio of TEM-induced ad-3A and ad-3B mutations with those induced by EI has revealed a difference between the ad-3B/ad-3A ratios. Additional comparisons are made of the C1 NIOSH,DIV RESP DIS STUDIES,MICROBIOL SECT,MORGANTOWN,WV 26505. RP DESERRES, FJ (reprint author), NIEHS,DIV INTRMURAL RES,ENVIRONM TOXICOL PROGRAM,TOXICOL BRANCH,MD 19-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY PY 1995 VL 328 IS 2 BP 193 EP 205 DI 10.1016/0027-5107(95)00008-7 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA QW540 UT WOS:A1995QW54000007 PM 7739603 ER PT J AU WANG, SB SUN, CE WALCZAK, CA ZIEGLE, JS KIPPS, BR GOLDIN, LR DIEHL, SR AF WANG, SB SUN, CE WALCZAK, CA ZIEGLE, JS KIPPS, BR GOLDIN, LR DIEHL, SR TI EVIDENCE FOR A SUSCEPTIBILITY LOCUS FOR SCHIZOPHRENIA ON CHROMOSOME 6PTER-P22 SO NATURE GENETICS LA English DT Article ID PEDIGREE-MEMBER METHOD; LINKAGE ANALYSIS; GENETIC-LINKAGE; ROSCOMMON FAMILY; RELATIVES; POLYMORPHISM; STRATEGIES; REGION AB We have performed linkage analysis in 186 multiplex families to search for genes that predispose to schizophrenia. Under a model with partially dominant inheritance, moderately broad disease definition and assuming locus homogeneity, a lod score of 3.2 was obtained for D6S260 on chromosome 6p23. A multipoint lod score of 3.9 (P=2.3 x 10(-5)) was achieved when the F13A1 and D6S260 loci were analysed, allowing for locus heterogeneity. Adjusted for testing of multiple models, the multipoint lod score of 3.9 under heterogeneity has a genome wide significance of between 5-8%. The nonparametric affected pedigree member test provided. results (P=3 x 10(-4)) also supporting this finding. Our findings provide supportive evidence for a susceptibility locus for schizophrenia on distal chromosome 6p, and support a model of locus heterogeneity. C1 NIDR,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. PERKIN ELMER CORP,DIV APPL BIOSYST,FOSTER CITY,CA 94404. VIRGINIA COMMONWEALTH UNIV,SCH DENT,CLIN PERIODONTAL DIS RES CTR,RICHMOND,VA 23298. FU NCRR NIH HHS [RR03655]; NIMH NIH HHS [MH41953, MH45390] NR 44 TC 218 Z9 226 U1 3 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1995 VL 10 IS 1 BP 41 EP 46 DI 10.1038/ng0595-41 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QX573 UT WOS:A1995QX57300014 PM 7647789 ER PT J AU RANADE, K HUSSUSSIAN, CJ SIKORSKI, RS VARMUS, HE GOLDSTEIN, AM TUCKER, MA SERRANO, M HANNON, GJ BEACH, D DRACOPOLI, NC AF RANADE, K HUSSUSSIAN, CJ SIKORSKI, RS VARMUS, HE GOLDSTEIN, AM TUCKER, MA SERRANO, M HANNON, GJ BEACH, D DRACOPOLI, NC TI MUTATIONS ASSOCIATED WITH FAMILIAL MELANOMA IMPAIR P16(INK4) FUNCTION SO NATURE GENETICS LA English DT Letter ID DYSPLASTIC NEVUS; LOCUS C1 WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,HOWARD HUGHES MED INST,COLD SPRING HARBOR,NY 11724. SEQUANA THERAPEUT INC,LA JOLLA,CA 92037. RP RANADE, K (reprint author), NATL CTR HUMAN GENOME RES,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015; Serrano, Manuel/H-2634-2015 OI Serrano, Manuel/0000-0001-7177-9312 NR 17 TC 238 Z9 242 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1995 VL 10 IS 1 BP 114 EP 116 DI 10.1038/ng0595-114 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA QX573 UT WOS:A1995QX57300026 PM 7647780 ER PT J AU ROTH, GS INGRAM, DK LANE, MA AF ROTH, GS INGRAM, DK LANE, MA TI SLOWING AGING BY CALORIC RESTRICTION SO NATURE MEDICINE LA English DT Editorial Material ID DIETARY RESTRICTION AB Dietary caloric restriction is the only intervention conclusively shown to slow ageing, delay the onset of age-related diseases, maintain function and extend both median and maximal life span in mammals. RP ROTH, GS (reprint author), JOHNS HOPKINS UNIV,NIA,GERONTOL RES CTR,BAYVIEW CAMPUS,BALTIMORE,MD 21224, USA. NR 17 TC 43 Z9 46 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1995 VL 1 IS 5 BP 414 EP 415 DI 10.1038/nm0595-414 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RN100 UT WOS:A1995RN10000028 PM 7585085 ER PT J AU LEWIS, W DALAKAS, MC AF LEWIS, W DALAKAS, MC TI MITOCHONDRIAL TOXICITY OF ANTIVIRAL DRUGS SO NATURE MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-POLYMERASES; MUSCLE MITOCHONDRIA; ZIDOVUDINE THERAPY; AIDS; AZIDOTHYMIDINE; MYOPATHY; AZT; DISORDERS; 2',3'-DIDEOXYCYTIDINE AB Long-term treatment with antiviral nucleoside analogue drugs, such as AZT, can give rise to delayed and at times severe mitochondrial toxicity. Although these toxic effects are manifest in many tissues, a common disease mechanism can explain the diverse clinical events. A better understanding of these disorders will shed light on genetic mitochondrial diseases and lead to the design of safer and more effective antiviral drugs. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. RP LEWIS, W (reprint author), UNIV CINCINNATI,COLL MED,DEPT PATHOL & LAB MED,CINCINNATI,OH 45267, USA. NR 66 TC 538 Z9 547 U1 0 U2 14 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1995 VL 1 IS 5 BP 417 EP 422 DI 10.1038/nm0595-417 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RN100 UT WOS:A1995RN10000030 PM 7585087 ER PT J AU DING, JP DAS, K MOEREELS, H KOYMANS, L ANDRIES, K JANSSEN, PAJ HUGHES, SH ARNOLD, E AF DING, JP DAS, K MOEREELS, H KOYMANS, L ANDRIES, K JANSSEN, PAJ HUGHES, SH ARNOLD, E TI STRUCTURE OF HIV-1 RT/TIBO R-86183 COMPLEX REVEALS SIMILARITY IN THE BINDING OF DIVERSE NONNUCLEOSIDE INHIBITORS SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; REPLICATION; DERIVATIVES; POTENT; SERIES AB We report the structure of HIV-I reverse transcriptase (RT) complexed with the nonnucleoside inhibitor TIBO R 86183 at 3.0 Angstrom resolution. Comparing this structure with those of complexes of HIV-1 RT/alpha-APA R 95845 and HIV-1 RT/nevirapine provides a basis for understanding the nature of nonnucleoside inhibitor binding, the structure of the binding site and the interactions between the bound inhibitors and surrounding amino acid residues as well as for understanding mechanisms of inhibition by and resistance to nonnucleoside inhibitors. Ail three inhibitors considered assume a similar butterfly-like shape and bind to HIV-1 RT in a very similar way. important differences occur in the conformation of amino acid residues that form the binding pocket. C1 CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01 CO 46000]; NIAID NIH HHS [AI 27690, AI 36144] NR 33 TC 267 Z9 276 U1 2 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 1995 VL 2 IS 5 BP 407 EP 415 DI 10.1038/nsb0595-407 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RF667 UT WOS:A1995RF66700016 PM 7545077 ER PT J AU GALLO, V PENDE, M SCHERER, S MOLNE, M WRIGHT, P AF GALLO, V PENDE, M SCHERER, S MOLNE, M WRIGHT, P TI EXPRESSION AND REGULATION OF KAINATE AND AMPA RECEPTORS IN UNCOMMITTED AND COMMITTED NEURAL PROGENITORS SO NEUROCHEMICAL RESEARCH LA English DT Review DE GLUTAMATE; DEVELOPMENT; IMMEDIATE EARLY GENES; GENE TRANSCRIPTION ID AMINO-ACID RECEPTORS; CULTURED RAT ASTROCYTES; CENTRAL-NERVOUS-SYSTEM; SELECTIVE GLUTAMATE RECEPTORS; AMYOTROPHIC-LATERAL-SCLEROSIS; PRIMARY RESPONSE GENES; HUMAN CELL-LINE; CHROMOSOMAL LOCALIZATION; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING AB Here we review experimental evidence of non-NMDA glutamate receptor expression in the embryonic central nervous system. AMPA- and kainate-preferring glutamate receptor subunit mRNA transcripts are detected in embryonic neurons, glia and neural progenitors. Functional assays demonstrate that in some cell subpopulations ionotropic glutamate receptors are expressed by;progenitors before synapse formation and terminal differentiation, and may be present before lineage determination is specified. The activation of these receptors triggers induction of immediate early gene transcription in progenitor cells. The cloning and transcriptional analysis of upstream regulatory regions of glutamate receptor genes governing their temporal and tissue-specific expression are also discussed. RP GALLO, V (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,NEUROBIOL UNIT,BLDG 49,ROOM 5A 78,BETHESDA,MD 20892, USA. NR 138 TC 27 Z9 27 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1995 VL 20 IS 5 BP 549 EP 560 DI 10.1007/BF01694536 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QY667 UT WOS:A1995QY66700005 PM 7643960 ER PT J AU SPERGEL, DJ KRSMANOVIC, LZ STOJILKOVIC, SS CATT, KJ AF SPERGEL, DJ KRSMANOVIC, LZ STOJILKOVIC, SS CATT, KJ TI L-TYPE CA2+ CHANNELS MEDIATE JOINT MODULATION BY GAMMA-AMINOBUTYRIC-ACID AND GLUTAMATE OF [CA2+], AND NEUROPEPTIDE SECRETION IN IMMORTALIZED GONADODROPIN-RELEASING HORMONE NEURONS SO NEUROENDOCRINOLOGY LA English DT Article DE CALCIUM; GAMMA-AMINOBUTYRIC ACID; GLUTAMATE; GONADOTROPIN-RELEASING HORMONE; GT1-7 CELLS ID NEUROENDOCRINE REGULATION; EXCITATORY TRANSMITTER; INTRACELLULAR CA-2+; RECEPTOR SUBTYPES; GNRH NEURONS; AMINO-ACIDS; GABA; CELLS; CATECHOLAMINES; AGONISTS AB To examine the role of calcium signaling in the joint modulation of gonadotropin-releasing hormone (GnRH) secretion by gamma-aminobutyric acid (GABA) and glutamate, cytoplasmic calcium ([Ca2+](i)) responses to the two transmitters were analyzed in monolayer networks of the GT1-7 line of immortalized GnRH neurons. [Ca2+](i) was increased by GABA and the GABA(A) receptor agonist, muscimol, and these responses were inhibited by the GABA(A) receptor antagonist, bicuculline. In contrast, the GABA(B) receptor agonist, baclofen, and the GABA(B) receptor antagonist, phaclofen, had no effect on basal and GABA- and glutamate-induced Ca2+ levels in GT1-7 neurons. The GABA-and muscimol-induced responses consisted of a spike increase in [Ca2+](i) followed by a decrease to a plateau; both the increase and the subsequent decrease in [Ca2+](i) depended on agonist concentration. Glutamate, N-methyl-D-aspartate (NMDA), and kainate also increased [Ca2+](i), but were less effective than GABA. GABA-, glutamate-, NMDA-, and kainate-induced [Ca2+](i) responses were almost abolished in Ca2+-free medium and were markedly attenuated by nifedipine. The [Ca2+](i) response to GABA was unaffected by prior application of glutamate, and vice versa. This additive effect of glutamate on the GABA-induced [Ca2+](i) response was mimicked by prior or simultaneous application of low (10 mM) KCl. The [Ca2+](i) response to simultaneous application of GABA and glutamate was also equal to the sum of the individual responses, whereas the GnRH secretory response was larger. However, the secretory responses to GABA and glutamate applied individually or together, were markedly attenuated by nifedipine. These results indicate that in GT1-7 neurons the combined actions of GABA and glutamate on [Ca2+](i) are additive of the actions of each transmitter, which are nifedipine-sensitive. However, the combined actions of the two transmitters on GnRH release are more than additive, possibly reflecting the non-linear coupling between [Ca2+](i) and exocytosis in neuroendocrine cells. RP SPERGEL, DJ (reprint author), NICHHD,ERRB,BLDG 49,RM 6A36,BETHESDA,MD 20892, USA. RI Spergel, David/A-4410-2011 NR 35 TC 34 Z9 34 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1995 VL 61 IS 5 BP 499 EP 508 DI 10.1159/000126873 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA QY536 UT WOS:A1995QY53600004 PM 7617127 ER PT J AU SEI, Y VITKOVIC, L YOKOYAMA, MM AF SEI, Y VITKOVIC, L YOKOYAMA, MM TI CYTOKINES IN THE CENTRAL-NERVOUS-SYSTEM - REGULATORY ROLES IN NEURONAL FUNCTION, CELL-DEATH AND REPAIR SO NEUROIMMUNOMODULATION LA English DT Review DE AIDS; ALZHEIMERS DISEASE; APOPTOSIS; CYTOKINE; LONG-TERM POTENTIATION; NEURONAL DEGENERATION; PROGRAMMED CELL DEATH ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM POTENTIATION; TRANSFORMING GROWTH FACTOR-BETA-1; GUILLAIN-BARRE-SYNDROME; INTERNUCLEOSOMAL DNA CLEAVAGE; IMMUNE-DEFICIENCY SYNDROME; HUMAN-FETAL ASTROCYTES; NITRIC-OXIDE SYNTHASE; II MUTANT MICE AB Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e. g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases. C1 NIMH,DIV NEUROSCI & BEHAV SCI,BETHESDA,MD 20892. KAGOSHIMA UNIV,SCH MED,DEPT VIROL,KAGOSHIMA 890,JAPAN. RP SEI, Y (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 158 TC 71 Z9 72 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD MAY-JUN PY 1995 VL 2 IS 3 BP 121 EP 133 DI 10.1159/000096881 PG 13 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA TH750 UT WOS:A1995TH75000001 PM 8646560 ER PT J AU WONG, ML BONGIORNO, PB GOLD, PW LICINIO, J AF WONG, ML BONGIORNO, PB GOLD, PW LICINIO, J TI LOCALIZATION OF INTERLEUKIN-1-BETA CONVERTING-ENZYME MESSENGER-RNA IN RAT-BRAIN VASCULATURE - EVIDENCE THAT THE GENES ENCODING THE INTERLEUKIN-1 SYSTEM ARE CONSTITUTIVELY EXPRESSED IN BRAIN BLEED VESSELS - PATHOPHYSIOLOGICAL IMPLICATIONS SO NEUROIMMUNOMODULATION LA English DT Article DE INTERLEUKIN-1; IN SITU HYBRIDIZATION; VASCULAR ENDOTHELIUM; BRAIN; INTERLEUKIN-1 RECEPTORS; INTERLEUKIN-1 CONVERTING ENZYME; MESSENGER RNA; RNA PROBES ID SMOOTH-MUSCLE CELLS; RECEPTOR ANTAGONIST; MESSENGER-RNA; NITRIC-OXIDE; MOLECULAR-CLONING; ENDOTHELIAL-CELLS; RABBIT; MECHANISM; ADHESION; DNA AB Interleukin (IL)-1 beta-converting enzyme (ICE) cleaves the biologically inactive precursor form of IL-1 beta into mature, bioactive IL-1 beta. Because of the potent effects of IL-1 in blood vessels, we conducted an in situ hybridization study to determine whether ICE mRNA is constitutively expressed in adult rat brain vasculature, Using in situ hybridization histochemistry, we were able to demonstrate that mRNA in blood vessels scattered throughout the brain, In a second set experiments, we found that the genes encoding not only ICE, but also IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), and the IL-1 type I receptor are expressed in brain vasculature. To our knowledge this is the first report documenting the expression of the genes encoding all of the functional elements of the IL-1 system in the same tissue. Our findings have three pathophysiological implications. First, they indicate a possible site where peripheral IL-1 may act in the brain. The vascular IL-1 system stimulates the production of nitric oxide and prostanoids, which could act as mediators of the effects of peripheral IL-1 in the central nervous system. Additionally, vascular IL-1 is known to activate adhesion molecules; our data that the genes encoding the IL-1 system are expressed in brain vasculature further support the concept that IL-1 is implicated in the pathophysiology of atherosclerosis and stroke. Finally, in the context of previous studies documenting that IL-1ra inhibits the effects of IL-1 on endothelial cells, our findings of endogenous IL-1ra mRNA in brain vasculature indicate that IL-1ra might be an endogenous vascular protective agent. RP WONG, ML (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROENDOCRINOL BRANCH,CNE,BLDG 10,RM 3S231,10 CTR DR,MSC 1284,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 45 TC 34 Z9 35 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD MAY-JUN PY 1995 VL 2 IS 3 BP 141 EP 148 DI 10.1159/000096884 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA TH750 UT WOS:A1995TH75000004 PM 8646563 ER PT J AU GARCES, Y BRILEY, EM FELDER, CC AF GARCES, Y BRILEY, EM FELDER, CC TI VASOPRESSIN VIA RECEPTOR-STIMULATED PHOSPHOLIPASE-D - DIFFERENTIAL REGULATION OF TRANSPHOSPHATIDYLATION AND PHOSPHOLIPID HYDROLYSIS BY PROTEIN-KINASE-C SO NEUROPEPTIDES LA English DT Article ID VASCULAR SMOOTH-MUSCLE; PHOSPHATIDYLCHOLINE HYDROLYSIS; CHEMOTACTIC PEPTIDE; DIACYLGLYCEROL KINASE; SIGNAL TRANSDUCTION; HL-60 GRANULOCYTES; PHOSPHATIDATE; ACTIVATION; CELLS; PHOSPHATIDYLINOSITOL AB Phospholipase D belongs to a group of membrane associated phospholipases which have been shown to be activated by G-protein coupled neurotransmitter receptors. Phosphatidylcholine is the primary substrate for phospholipase D generating phosphatidic acid (PA) and choline. In the presence of 1% ethanol, phospholipase D catalyzes a transphosphatidylation reaction generating phosphatidylethanol (PEt) which is an indicator of phospholipase D activation. In the present study, we utilized Chinese hamster ovary (CHO) cells stably transfected with and expressing a rat V1a vasopressin receptor to study the regulation of phospholipase D by protein kinase C and calcium. Arginine-vasopressin (AVP) stimulated the release of H-3-PEt and H-3-PA in cells pre-labelled overnight with 3H-palmitic acid. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated the release of PEt and PA that was additive with AVP over 15 min. However, long-term stimulation with PMA, which desensitizes protein kinase C, decreased PEt production while simultaneously increasing PA production. Differential regulation of PEt and PA production by PMA suggests the existence of more than one phospholipase D isoenzyme. Though differentially regulated by protein kinase C, both AVP-stimulated PEt and PA production required extracellular and not intracellular calcium. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED SCHOLARS PROGRAM,BETHESDA,MD. NR 25 TC 2 Z9 2 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 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD MAY PY 1995 VL 28 IS 5 BP 277 EP 285 DI 10.1016/0143-4179(95)90044-6 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA QX138 UT WOS:A1995QX13800004 PM 7603588 ER PT J AU BLIN, J CHASE, T AF BLIN, J CHASE, T TI EFFECTS OF SCOPOLAMINE ON HUMAN BRAIN GLUCOSE CONSUMPTION SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter C1 NIH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP BLIN, J (reprint author), UNIV LOUVAIN,BRUSSELS,BELGIUM. NR 6 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1995 VL 12 IS 3 BP 273 EP 274 DI 10.1038/sj.npp.1380261 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QW223 UT WOS:A1995QW22300009 PM 7612162 ER PT J AU MOLCHAN, SE SUNDERLAND, T MATOCHIK, JA ZAMETKIN, AJ COHEN, RM AF MOLCHAN, SE SUNDERLAND, T MATOCHIK, JA ZAMETKIN, AJ COHEN, RM TI EFFECTS OF SCOPOLAMINE ON HUMAN BRAIN GLUCOSE CONSUMPTION - REPLY SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter C1 NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. RP MOLCHAN, SE (reprint author), NIMH,CLIN SCI LAB,GERIATR PSYCHIAT SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1995 VL 12 IS 3 BP 275 EP 276 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QW223 UT WOS:A1995QW22300010 ER PT J AU SCHWEICHLER, M HENNESSEY, JV COLE, P PERDUE, JF LEROITH, D AF SCHWEICHLER, M HENNESSEY, JV COLE, P PERDUE, JF LEROITH, D TI HYPOGLYCEMIA IN PREGNANCY SECONDARY TO A NON-ISLET CELL TUMOR OF THE PLEURA AND ECTOPIC INSULIN-LIKE GROWTH-FACTOR-II HORMONE PRODUCTION SO OBSTETRICS AND GYNECOLOGY LA English DT Note AB Background: In nondiabetic women, pregnancy alone rarely causes clinical hypoglycemia. Non-islet cell tumors have recently been shown to be associated with the production of insulin-like growth factor II (IGF-II) and a paraneoplastic syndrome resulting in hypoglycemia. A case report and review of pathophysiologic mechanisms involved is presented. Case: A 38-year-old multigravida presented suffering from clinical and biochemical hypoglycemia, which was found to be secondary to a mesothelioma of the pleura and ectopic IGF-II production. Tumor resection was performed during the 13th gestational week. The mother became euglycemic immediately after the surgery and remained asymptomatic. Clinical indicators of pregnancy and an ultrasound scan after the surgery were consistent with a normal viable fetus. Conclusion: Symptomatic hypoglycemia and other medical conditions occurring during pregnancy require immediate diagnosis and treatment. In addition to the more common causes, documented cases of medical conditions due to paraneoplastic syndromes of ectopic hormone production during pregnancy have been described. This case establishes the non-islet cell tumor with IGF-II-induced hypoglycemia as another such syndrome to be considered when evaluating hypoglycemia in pregnancy. C1 BROWN UNIV,DIV ENDOCRINOL,PROVIDENCE,RI. BRIGHAM & WOMENS HOSP,DIV ENDOCRINOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. AMER RED CROSS,JEROME H HOLLAND LAB,BETHESDA,MD. NIH,DIABET BRANCH,BETHESDA,MD. NR 13 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1995 VL 85 IS 5 SU S BP 810 EP 813 DI 10.1016/0029-7844(94)00313-3 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QU963 UT WOS:A1995QU96300002 PM 7724120 ER PT J AU Funakoshi, S Beckwith, M Fanslow, W Longo, DL Murphy, WJ AF Funakoshi, S Beckwith, M Fanslow, W Longo, DL Murphy, WJ TI Epstein-Barr virus-induced human B-cell lymphoma arising in HuPBL-SCID chimeric mice: Characterization and the role of CD40 stimulation in their treatment and prevention SO PATHOBIOLOGY LA English DT Article DE CD40; Epstein-Barr virus; lymphomagenesis; B lymphoma; SCID mice; p53 ID GROWTH-INHIBITION; ACTIVATION; EXPRESSION; CYTOKINES; ANTIBODY; RECEPTOR; PROTEIN AB The transfer of human peripheral blood lymphocytes (huPBL) from EBV-seropositive donors into mice with severe combined immune deficiency (SCID) has been shown previously to result in the generation of human EBV-induced B-cell lymphomas, These lymphomas are similar to the aggressive lymphomas that arise clinically in immunocompromised individuals, We have assessed the p53 status of these human B-lymphomas and the clonality of cell lines established from tumors growing in the huPBL-SCID mice, While the lymphoma cell lines were demonstrated to be pauciclonal by Southern analysis, none of the lines demonstrated mutated p53 as determined by immunoprecipitation studies using antibodies specific for mutant p53, The cell lines were all positive for CD40, a marker present on normal and neoplastic B cells, Antibodies to CD40 significantly inhibited the growth of these EBV-transformed B-cell lymphomas both in vitro and in vivo, When partially purified human B cells were incubated with either anti-CD40 or anti-IgM in the presence of EBV-containing supernatants in vitro, only anti-CD40 prevented transformation by EBV, Treatment of huPBL-SCID mice with anti-CD40 also prevented the occurrence of the EBV lymphomas, However, long-term human B-cell engraftment was not inhibited as determined by the presence of serum human immunoglobulin in the chimeric mice, Overnight incubation of the huPBL with anti-CD40 did not prevent the incidence of lymphomas in huPBL-SCID chimeras suggesting that continuous exposure to anti-CD40 is required, These studies suggest that anti-CD40 may be of significant clinical use in the treatment or prevention of EBV-induced B-cell lymphomas. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL RESPONSE MODIFERS PROGRAM,FREDERICK,MD 21702. IMMUNEX CORP,SEATTLE,WA. NR 25 TC 13 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAY-JUN PY 1995 VL 63 IS 3 BP 133 EP 142 DI 10.1159/000163944 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA UE359 UT WOS:A1995UE35900003 PM 8821629 ER PT J AU FISH, DN PISCITELLI, SC DANZIGER, LH AF FISH, DN PISCITELLI, SC DANZIGER, LH TI DEVELOPMENT OF RESISTANCE DURING ANTIMICROBIAL THERAPY - A REVIEW OF ANTIBIOTIC CLASSES AND PATIENT CHARACTERISTICS IN 173 STUDIES SO PHARMACOTHERAPY LA English DT Review ID URINARY-TRACT INFECTIONS; SERIOUS BACTERIAL-INFECTIONS; IMIPENEM CILASTATIN THERAPY; ORAL CIPROFLOXACIN THERAPY; GRAM-NEGATIVE INFECTIONS; SOFT-TISSUE INFECTIONS; PSEUDOMONAS-AERUGINOSA INFECTIONS; FEBRILE GRANULOCYTOPENIC PATIENTS; CEFOPERAZONE PLUS PIPERACILLIN; BETA-LACTAM THERAPY AB The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem-cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates were Pseudomonas aeruginosa, Serratia, Enterobacter, and Acinetobacter sp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistance. C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT PHARM PRACTICE,CHICAGO,IL. RP FISH, DN (reprint author), UNIV COLORADO,HLTH SCI CTR,SCH MED,DEPT PHARM PRACTICE,CAMPUS BOX C-238,4200 E NINTH AVE,DENVER,CO 80262, USA. NR 196 TC 96 Z9 101 U1 1 U2 12 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY-JUN PY 1995 VL 15 IS 3 BP 279 EP 291 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RA453 UT WOS:A1995RA45300003 PM 7667163 ER PT J AU MASOLIVER, J ROBINSON, A WEISS, GH AF MASOLIVER, J ROBINSON, A WEISS, GH TI COHERENT STOCHASTIC RESONANCE SO PHYSICAL REVIEW E LA English DT Article C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP MASOLIVER, J (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 10 TC 12 Z9 12 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD MAY PY 1995 VL 51 IS 5 BP 4021 EP 4026 DI 10.1103/PhysRevE.51.4021 PN A PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA QZ153 UT WOS:A1995QZ15300032 ER PT J AU KRISTAL, AR PATTERSON, RE GLANZ, K HEIMENDINGER, J HEBERT, JR FENG, ZD PROBART, C AF KRISTAL, AR PATTERSON, RE GLANZ, K HEIMENDINGER, J HEBERT, JR FENG, ZD PROBART, C TI PSYCHOSOCIAL CORRELATES OF HEALTHFUL DIETS - BASE-LINE RESULTS FROM THE WORKING WELL STUDY SO PREVENTIVE MEDICINE LA English DT Article ID BEHAVIOR-CHANGE; MODELS AB Background. This report examines psychosocial factors related to selection of healthful diets. Understanding why people select healthful diets can lead to rational design and evaluation of nutrition intervention programs. Methods. Data are from 16,287 respondents to the baseline survey for the Working Well Trial, a randomized, controlled trial of worksite-based health promotion. The psychosocial constructs we measured were predisposing factors (beliefs, perceived benefits, and motivation; 5 items, Cronbach's alpha = 0.65) and enabling factors (barriers, norms, and social support; 6 items, Cronbach's alpha = 0.57). The healthful diet outcomes were intakes of fat, fiber, and servings of fruits and vegetables (from a food frequency questionnaire) and intention and self-efficacy to decrease fat and increase fruits and vegetables. Results. Based on a 5-point scale (1 = low to 5 = high), the mean predisposing factor scale score was much higher than the enabling factor scale score (3.77 vs 2.50, P < 0.001). Comparing respondents in the highest category of the predisposing scale to those in the lowest, mean percentage of energy from fat was 22.4% lower (-9 percentage points), fiber was 85.2% higher (+4.6 g/1,000 kcal), and fruits and vegetables were 100% higher (+1.6 servings/day) (all trends, P < 0.001). Associations were similar, but much weaker, for the enabling scale. Multiple regression models, which included covariates related to diet and the predisposing and enabling scales, explained a total of between 13 and 26% of the variance in diet and intention to change diet. After control for covariates, the predisposing scale remained a significant and strong predictor of diet and intention to change diet but the enabling scale explained small and nonsignificant amounts of variance. Conclusions. Predisposing factors are strong predictors of current diet and intention to change diet. Final results from the Working Well Trial will provide more information on whether enabling factors can be enhanced by intervention and whether these changes result in healthier eating patterns. (C) 1995 Academic Press, Inc. C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA. UNIV HAWAII,CANC RES CTR HAWAII,HONOLULU,HI 96813. NCI,BETHESDA,MD. UNIV MASSACHUSETTS,WORCESTER,MA. PENN STATE COLL,STATE COLL,PA. RP KRISTAL, AR (reprint author), FRED HUTCHINSON CANC RES CTR,1124 COLUMBIA ST,MP 702,SEATTLE,WA 98104, USA. RI Kristal, Alan/A-8779-2008; OI Kristal, Alan/0000-0002-7329-1617 NR 34 TC 74 Z9 76 U1 2 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 1995 VL 24 IS 3 BP 221 EP 228 DI 10.1006/pmed.1995.1037 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA RA864 UT WOS:A1995RA86400002 PM 7644443 ER PT J AU KUROCHKINA, N LEE, B AF KUROCHKINA, N LEE, B TI HYDROPHOBIC POTENTIAL BY PAIRWISE SURFACE-AREA SUM SO PROTEIN ENGINEERING LA English DT Article DE ACCESSIBLE SURFACE AREA; HYDROPHOBIC POTENTIAL; PROTEIN FOLDING ID GLOBULAR-PROTEINS; EXCLUDED VOLUME; AMINO-ACIDS; SOLVENT; APPROXIMATION; SOLUBILITY AB An approximate but rapid method for estimating hydrophobic energy is proposed, Aside from a scale factor, it is given by the pairwise sum of the surface area buried by each neighbor atom, but excluding those atoms in the same residue or in its sequence neighbor residues, This sum is found to be linearly related to the true buried area as calculated by the algorithm of Lee and Richards [1971, J, Mel. Biol,, 55, 379-400], and to the contact potential of Miyazawa and Jernigan [1985, Macromolecules, 18, 534-552], It correlates with experimental transfer free energies to approximately the same degree as that calculated using the true buried area, Furthermore, in a simple test of helix packing with ROP protein monomer, the new hydrophobic energy clearly discriminated one structure, with the lowest r.m.s, deviation from the crystal structure, against an exhaustive set of others. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 21 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1995 VL 8 IS 5 BP 437 EP 442 DI 10.1093/protein/8.5.437 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RN591 UT WOS:A1995RN59100004 PM 8532664 ER PT J AU JUCOVIC, M HARTLEY, RW AF JUCOVIC, M HARTLEY, RW TI IN-VIVO SYSTEM FOR THE DETECTION OF LOW-LEVEL ACTIVITY BARNASE MUTANTS SO PROTEIN ENGINEERING LA English DT Article DE ACTIVE-SITE MUTANT; BARSTAR; GENE INVERSION; RIBONUCLEASE; TIGHTLY CONTROLLED EXPRESSION ID PROMOTER INVERSION INVIVO; CLONED GENE-EXPRESSION; DIRECTED MUTAGENESIS; BARSTAR; SITE; RIBONUCLEASE; CONSTRUCTION AB We report the design of a new tightly controlled barnase system which allows the existence of the barnase gene in host cells without a signal sequence, When expression of barnase is turned on by gene inversion in vivo, the lethal effect of barnase (or its mutants) is not compromised either by coexpression of its polypeptide inhibitor (barstar), or by extracellular secretion, This serves as a rapid, sensitive in vivo test for the detection of any very low residual activity of the barnase mutants, Active-site mutants His102Lys, Glu73Asp and Arg87Lys, and a mutant which greatly reduces the stability and yield of protein, Arg83Lys, produce enough activity to be detectable by this test, In contrast, when expressed on a secretion vector, these mutants do not yield detectable activity in a solution assay, Truly inactive mutants, such as those of His102 to Gly, Ala or Leu, were completely harmless when expressed in this system. RP JUCOVIC, M (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1995 VL 8 IS 5 BP 497 EP 499 DI 10.1093/protein/8.5.497 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RN591 UT WOS:A1995RN59100012 PM 8532672 ER PT J AU CLUBB, RT OMICHINSKI, JG SAKAGUCHI, K APPELLA, E GRONENBORN, AM CLORE, GM AF CLUBB, RT OMICHINSKI, JG SAKAGUCHI, K APPELLA, E GRONENBORN, AM CLORE, GM TI BACKBONE DYNAMICS OF THE OLIGOMERIZATION DOMAIN OF P53 DETERMINED FROM N-15 NMR RELAXATION MEASUREMENTS SO PROTEIN SCIENCE LA English DT Article DE BACKBONE DYNAMICS; N-15 RELAXATION; P53; SOLUTION STRUCTURE ID MODEL-FREE APPROACH; SPECTROSCOPY; MUTATIONS; CANCER; INTERLEUKIN-1-BETA; SUPPRESSION; SIMULATION; PROTEINS; GENE AB The backbone dynamics of the tetrameric p53 oligomerization domain (residues 319-360) have been investigated by two-dimensional inverse detected heteronuclear H-1-N-15 NMR spectroscopy at 500 and 600 MHz. (NT1)-N-15, T-2, and heteronuclear NOEs were measured for 39 of 40 non-proline backbone NH vectors at both field strengths. The overall correlation time for the tetramer, calculated from the T-1/T-2 ratios, was found to be 14.8 ns at 35 degrees C. The correlation times and amplitudes of the internal motions were extracted from the relaxation data using the model-free formalism (Lipari G, Szabo A, 1982, J Am Chem Soc 104:4546-4559). The internal dynamics of the structural core of the p53 oligomerization domain are uniform and fairly rigid, with residues 327-354 exhibiting an average generalized order parameter (S-2) Of 0.88 +/- 0.08. The N- and C-termini exhibit substantial mobility and are unstructured in the solution structure of p53. Residues located at the N- and C-termini, in the beta-sheet, in the turn between the alpha-helix and beta-sheet, and at the C-terminal end of the alpha-helix display two distinct internal motions that are faster than the overall correlation time. Fast internal motions (less than or equal to 20 ps) are within the extreme narrowing limit and are of uniform amplitude. The slower motions (0.6-2.2 ns) are outside the extreme narrowing limit and vary in amplitude. Four residues at the tetramer interface exhibit a small degree of conformational averaging as evidenced by N-15 line broadening, possibly due to sliding or rolling of the helices at the interface of the two dimers that form the tetramer. C1 NIDDKD,CHEM PHYS LAB,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 45 TC 31 Z9 31 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1995 VL 4 IS 5 BP 855 EP 862 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QW981 UT WOS:A1995QW98100005 PM 7663341 ER PT J AU FUJINAGA, M CHERNAIA, MM TARASOVA, NI MOSIMANN, SC JAMES, MNG AF FUJINAGA, M CHERNAIA, MM TARASOVA, NI MOSIMANN, SC JAMES, MNG TI CRYSTAL-STRUCTURE OF HUMAN PEPSIN AND ITS COMPLEX WITH PEPSTATIN SO PROTEIN SCIENCE LA English DT Article DE ASPARTIC PROTEINASE; BINDING SITE; CRYSTAL STRUCTURE; INHIBITOR ID HUMAN CATHEPSIN-D; ASPARTIC PROTEINASES; PORCINE PEPSIN; HUMAN RENIN; SEQUENCE-ANALYSIS; 1.8-A RESOLUTION; INHIBITOR; REFINEMENT; BINDING; ENDOTHIAPEPSIN AB The three-dimensional crystal structure of human pepsin and that of its complex with pepstatin have been solved by X-ray crystallographic methods. The native pepsin structure has been refined with data collected to 2.2 Angstrom resolution to an R-factor of 19.7%. The pepsin:pepstatin structure has been refined with data to 2.0 Angstrom resolution to an R-factor of 18.5%. The hydrogen bonding interactions and the conformation adopted by pepstatin are very similar to those found in complexes of pepstatin with other aspartic proteinases. The enzyme undergoes a conformational change upon inhibitor binding to enclose the inhibitor more tightly. The analysis of the binding sites indicates that they form an extended tube without distinct binding pockets. By comparing the residues on the binding surface with those of the other human aspartic proteinases, it has been possible to rationalize some of the experimental data concerning the different specificities. At the S1 site, valine at position 120 in renin instead of isoleucine, as in the other enzymes, allows for binding of larger hydrophobic residues. The possibility of multiple conformations for the P2 residue makes the analysis of the S2 site difficult. However, it is possible to see that the specific interactions that renin makes with histidine at P2 would not be possible in the case of the other enzymes. At the S3 site, the smaller volume that is accessible in pepsin compared to the other enzymes is consistent with its preference for smaller residues at the P3 position. C1 UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB T6G 2H7,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 54 TC 100 Z9 104 U1 5 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1995 VL 4 IS 5 BP 960 EP 972 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QW981 UT WOS:A1995QW98100016 PM 7663352 ER PT J AU WEINGARTNER, HJ SIROCCO, K RAWLINGS, R JOYCE, E HOMMER, D AF WEINGARTNER, HJ SIROCCO, K RAWLINGS, R JOYCE, E HOMMER, D TI DISSOCIATIONS IN THE EXPRESSION OF THE SEDATIVE EFFECTS OF TRIAZOLAM SO PSYCHOPHARMACOLOGY LA English DT Article DE BENZODIAZEPINES; EXPLICIT MEMORY; REFLECTIVE PROCESSES; SEDATION; TRIAZOLAM ID MULTIPLE MEMORY-SYSTEMS; IMPLICIT MEMORY; INDUCED AMNESIA; DIAZEPAM; BENZODIAZEPINES; SCOPOLAMINE; SENSITIVITY; IMPAIRMENTS; VOLUNTEERS; BEHAVIOR AB Fifteen normal volunteers were administered 0.250, 0.375, and 0.500 mg of triazolam and placebo in a double-blind repeated measures cross-over design. Subjects demonstrated dose-dependent impairments in free recall, a test of explicit memory requiring awareness and reflection, and sedation as assessed by objective behavioral measures (the digit symbol substitution task) and subjective visual analogue scales. The sedative drug response did not account for the impairment in free recall. Differences in performance of the two tests of sedation indicated that the effect of this drug on reflective processes accounts for impairment in episodic memory and the inability to track the sedative effects of this drug at the higher doses tested in this study. C1 CHARING CROSS & WESTMINSTER MED SCH,ACAD DEPT PSYCHIAT,LONDON,ENGLAND. NIAAA,LCS,BRAIN IMAGING SECT,BETHESDA,MD 20892. RP WEINGARTNER, HJ (reprint author), NIAAA,LCS,COGNIT NEUROSCI SECT,BLDG 10,ROOM 3B19,9000 ROCKVILLE PIKE,BETHESDA,MD 20982, USA. NR 32 TC 14 Z9 14 U1 2 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 1995 VL 119 IS 1 BP 27 EP 33 DI 10.1007/BF02246050 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QY587 UT WOS:A1995QY58700005 PM 7675946 ER PT J AU SHEAHAN, MD AF SHEAHAN, MD TI PREVENTION IN POLAND - HEALTH-CARE SYSTEM REFORM SO PUBLIC HEALTH REPORTS LA English DT Article AB Despite the political and economic reforms that have swept Eastern Europe in the past 5 years, there has been little change in Poland's health care system. The Ministry of Health and Social Welfare has targeted preventive care as a priority, yet the enactment of legislation to meet this goal has been slow. The process of reform has been hindered by political stagnation, economic crisis, and a lack of delineation of responsibility for implementing the reforms. Despite the delays in reform, recent developments indicate that a realistic, sustainable restructuring of the health care system is possible, with a focus on preventive services. Recent proposals for change have centered on applying national goals to limited geographic areas, with both local and international support. Regional pilot projects to restructure health care delivery at a community level, local health education and disease prevention initiatives, and a national training program for primary care and family physicians and nurses are being planned. Through regionalization, an increase in responsibility for both the physician and the patient, and redefinition of primary health care and the role of family physicians, isolated local movements and pilot projects have shown promise in achieving these goals, even under the current budgetary constraints. RP SHEAHAN, MD (reprint author), NIH,CTR HUMAN GENOME RES,BLDG 49,ROOM 4B83,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1995 VL 110 IS 3 BP 289 EP 294 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RE043 UT WOS:A1995RE04300009 PM 7610217 ER PT J AU MOSS, N AF MOSS, N TI REPORT ON THE CONFERENCE OF THE NATIONAL-INSTITUTES-OF-HEALTH SO PUBLIC HEALTH REPORTS LA English DT Editorial Material C1 KAISER FDN,RES INST,LOS ANGELES,CA. RP MOSS, N (reprint author), NIH,BEHAV & SOCIAL RES PROGRAM,GATEWAY BLDG,ROOM 533,BETHESDA,MD 20892, USA. NR 0 TC 27 Z9 27 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1995 VL 110 IS 3 BP 302 EP 305 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RE043 UT WOS:A1995RE04300014 ER PT J AU ADAMS, EM CHOW, CK PREMKUMAR, A PLOTZ, PH AF ADAMS, EM CHOW, CK PREMKUMAR, A PLOTZ, PH TI THE IDIOPATHIC INFLAMMATORY MYOPATHIES - SPECTRUM OF MR-IMAGING FINDINGS SO RADIOGRAPHICS LA English DT Article DE DERMATOMYOSITIS; MUSCLES, DISEASES; MYOSITIS ID SKELETAL-MUSCLE; DERMATOMYOSITIS; POLYMYOSITIS; MYOSITIS; RHABDOMYOLYSIS; EXERCISE; DISEASE AB Magnetic resonance (MR) imaging is useful for demonstrating the soft-tissue and musculature changes seen in patients with idiopathic inflammatory myopathies (IIMs), These changes include edema within and around muscle, subcutaneous reticulation, muscle calcification, and fatty infiltration of muscle, Muscle edema is visible as areas of hyperintensity on short inversion time inversion recovery (STIR) images, Abnormal reticulation of the subcutaneous tissue can be due to subcutaneous edema or an infiltrating process; edema from inflammation appears as areas of low signal intensity on T1-weighted images and as areas of high signal intensity on STIR images. Intramuscular calcium deposition appears as hypointense areas with all pulse sequences, On T1-weighted images, fatty infiltration appears as areas of high signal intensity within muscles, Because of the improved visualization of muscle inflammation provided by STIR imaging and because MR imaging is noninvasive, it has become a useful modality for evaluating patients with IIMs. C1 NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892. NR 32 TC 83 Z9 85 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY PY 1995 VL 15 IS 3 BP 563 EP 574 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QZ072 UT WOS:A1995QZ07200007 PM 7624563 ER PT J AU BROWN, ML FINTOR, L AF BROWN, ML FINTOR, L TI US SCREENING MAMMOGRAPHY SERVICES WITH MOBILE UNITS - RESULTS FROM THE NATIONAL SURVEY OF MAMMOGRAPHY FACILITIES SO RADIOLOGY LA English DT Article DE BREAST NEOPLASMS, DIAGNOSIS; BREAST RADIOGRAPHY, QUALITY ASSURANCE; BREAST RADIOGRAPHY, UTILIZATION; MOBILE FACILITIES; RADIOLOGY AND RADIOLOGISTS, SOCIOECONOMIC ISSUES AB PURPOSE: To investigate elements of mobile facilities for mammography in the United States. MATERIALS AND METHODS: The prevalence and performance of mobile facilities for mammography in the United States were studied with regard to cost, price, quality assurance, and access. Data were acquired from the National Cancer Institute's National Survey bf Mammography Facilities, conducted in 1992. RESULTS: Of the 1,057 facilities surveyed, 2.4% were identified as mobile and accounted for 3% of mammography examinations performed. All mobile facilities reported accreditation by the American College of Radiology, and 92% were in Statistically Metropolitan Areas. Most were affiliated with community hospitals or private radiology practice and were more likely to be associated with lower fees, convenient operating hours, batch interpretation, and computerized reporting than were their stationary counterparts. CONCLUSION: Mobile mammography facilities compare favorably with stationary facilities. The use of these mobile units in the United States, however, has been limited. RP BROWN, ML (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,APPL RES BRANCH,EXECUT PLAZA N,RM 313,BETHESDA,MD 20892, USA. NR 16 TC 22 Z9 23 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1995 VL 195 IS 2 BP 529 EP 532 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QU717 UT WOS:A1995QU71700040 PM 7724778 ER PT J AU SARTOR, BM SARTOR, O FLANDERS, KC AF SARTOR, BM SARTOR, O FLANDERS, KC TI ANALOGOUS TAMOXIFEN AND ESTROGEN EFFECTS ON TRANSFORMING GROWTH-FACTOR-BETA-1 AND GROWTH-FACTOR-BETA-2 IN THE RAT UTERUS SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE ESTROGEN; TRANSFORMING GROWTH FACTOR-BETA (TGF-BETA); RAT UTERUS; TAMOXIFEN ID HUMAN-BREAST-CANCER; MESSENGER-RNA; CELL-LINES; EXPRESSION; LOCALIZATION; ANTIBODIES AB Estrogenic stimulation is a potent risk factor for the development of uterine cancer. More recently, analysis of patients in prospective breast cancer trials have established that tamoxifen also increases uterine cancer risk. In this report, uteri of oophorectomized rats were examined to ascertain the effects of estrogen and tamoxifen on the uterine induction of two isoforms of transforming growth factor-beta (TGF-beta). In contrast to studies of cells derived from breast epithelium, our studies reveal that both estrogen and tamoxifen increase immunoreactive TGF-beta. These changes were particularly pronounced in the endometrial stroma. Effects of progesterone also were examined and found to be distinct and relatively restricted to the glandular epithelium. These studies indicate that, in the uteri of oophorectomized rats, tamoxifen exerts estrogen-like effects on a peptide previously implicated in the control of cellular growth and differentiation. We hypothesize that induction of TGF-beta isoforms may be an important mediatior of both estrogen- and tamoxifen-induced proliferative disorders in the uterus. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 30 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 1995 VL 9 IS 3 BP 225 EP 231 DI 10.1016/0890-6238(95)00003-S PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA RB716 UT WOS:A1995RB71600002 PM 7579906 ER PT J AU CERRITELLI, SM CROUCH, RJ AF CERRITELLI, SM CROUCH, RJ TI THE NON-RNASE-H DOMAIN OF SACCHAROMYCES-CEREVISIAE RNASE H1 BINDS DOUBLE-STRANDED-RNA - MAGNESIUM MODULATES THE SWITCH BETWEEN DOUBLE-STRANDED-RNA BINDING AND RNASE-H ACTIVITY SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE DIVALENT CATIONS; MUTAGENESIS; NORTHWESTERN BLOT; PROTEIN CONFORMATION; RNA-BINDING MOTIF; YEAST ID COLI RIBONUCLEASE-H; ESCHERICHIA-COLI; PROTEIN-KINASE; YEAST; IDENTIFICATION; POLYMERASE; DAI; EXPRESSION; GENES; SITE AB Eukaryotic ribonucleases H of known sequence are composed of an RNase H domain similar in size and sequence to that of Escherichia coli RNase HI and additional domains of unknown function. The RNase H1 of Saccharomyces cerevisiae has such an RNase H domain at its C-terminus. Here we show that the N-terminal non-RNase H portion of the yeast RNase H1 binds tightly to double-stranded RNA (dsRNA) and RNA-DNA hybrids even in the absence of the RNase H domain. Two copies of a sequence with limited similarity to the dsRNA-binding motif are present in this N-terminus. When the first of these sequences is altered, the protein no longer binds tightly to dsRNA and exhibits an increase in RNase H activity. Unlike other dsRNA-binding proteins, increasing the Mg2+ concentration from 0.5 mM to 5 mM inhibits binding of RNase H1 to dsRNA; yet a protein missing the RNase H domain binds strongly to dsRNA even at the higher Mg2+ concentration. These results suggest that binding to dsRNA and RNase H activity are mutually exclusive, and the Mg2+ concentration is critical for switching between the activities. Changes in the Mg2+ concentration or proteolytic severing of the dsRNA-binding domain could alter the activity or location of the RNase H and may govern access of the enzyme to the substrate. Sequences similar to the dsRNA-binding motif are present in other eukaryotic RNases H and the transactivating protein of cauliflower mosaic virus, suggesting that these proteins may also bind to dsRNA. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 35 TC 35 Z9 35 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 1995 VL 1 IS 3 BP 246 EP 259 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX401 UT WOS:A1995RX40100003 PM 7489497 ER PT J AU ALVAREZSALAS, LM LOPEZBAYGHEN, E AF ALVAREZSALAS, LM LOPEZBAYGHEN, E TI GENETIC-REGULATION OF HUMAN GENITAL PAPILLOMAVIRUS SO SALUD PUBLICA DE MEXICO LA Spanish DT Review DE PAPILLOMAVIRUS; ONCOGENES; GENE EXPRESSION REGULATION ID CERVICAL-CARCINOMA CELLS; TRANSCRIPTION FACTOR; BINDING-PROTEIN; DNA-REPLICATION; MUTATIONAL ANALYSIS; EPITHELIAL-CELLS; TYPE-18 ENHANCER; E6 PROTEINS; E2; EXPRESSION AB Human papillomavirus (HPV) specifically infect stratified epithelial cells, causing benign and malignant neoplasia. Several elements directing this virus' genetic expression are present in a non-coding region called LCR. HPV infection starts in the basal cells of stratified epithelia, where a particular combination of cellular factors interacting with the LCR starts the transcription of the viral E6 and E7 oncogenes. The Ed and E7 genes alter the cell cycle because they interact and inactivate tumor suppressor proteins: E6 binds and degrades protein p53 and E7 associates with p105(RB). E1 and E2 are the next synthesized proteins. E2 blocks the early transcription and permits E1 specific binding to the viral origin of replication located within the LCR, initiating the viral genome replication. Following the course of viral infection, the E2-induced E6 and E7 down-regulation releases p53 and p105(RB) proteins, and the differentiation process can continue. Then, a putative late promoter can activate the capsid genes L1 and L2. At this step, mature virions can be detected in the upper layers of the epithelium. Disruption in E2 gene transcription is usually associated to genital malignant neoplasia. In the absence of E2, E6 and E7 remain constitutively expressed, sustaining the immortality of the infected cell and blocking the epithelial differentiation program. C1 IPN,CTR INVEST & ESTUDIOS AVANZADOS,DEPT GENET & BIOL MOLEC,MEXICO CITY 07300,DF,MEXICO. NCI,BIOL LAB,BETHESDA,MD 20892. NR 48 TC 1 Z9 1 U1 0 U2 0 PU INST NACIONAL SALUD PUBLICA PI CUERNAVACA PA AV UNIVERSIDAD 655, COL SANTA MARIA AHUACATITLAN, CUERNAVACA 62508, MORELOS, MEXICO SN 0036-3634 J9 SALUD PUBLICA MEXICO JI Salud Publica Mexico PD MAY-JUN PY 1995 VL 37 IS 3 BP 240 EP 247 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RT683 UT WOS:A1995RT68300010 ER PT J AU KAJIMURA, N KATO, M OKUMA, T SEKIMOTO, M WATANABE, T TAKAHASHI, K AF KAJIMURA, N KATO, M OKUMA, T SEKIMOTO, M WATANABE, T TAKAHASHI, K TI A QUANTITATIVE SLEEP-EEG STUDY ON THE EFFECTS OF BENZODIAZEPINE AND ZOPICLONE IN SCHIZOPHRENIC-PATIENTS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE POLYSOMNOGRAM; PERIOD-AMPLITUDE ANALYSIS; BENZODIAZEPINE; ZOPICLONE; DELTA WAVE; (SCHIZOPHRENIA) ID ELECTROENCEPHALOGRAPHIC SLEEP; NEUROLEPTIC TREATMENT; DELTA ACTIVITY; CYCLOPYRROLONES; FLURAZEPAM; SURICLONE; SPINDLES AB Polysomnographic examinations (PSG) were performed on 6 male schizophrenic outpatients who were being treated with benzodiazepine (BZD) hypnotics in combination with neuroleptics and 6 healthy male volunteers. In schizophrenic subjects, zopiclone (ZPC), 15mg/day, was substituted for the BZD hypnotics, and PSGs were recorded again during ZPC therapy. Ah-night sleep stage scoring was carried out by visual analysis, and computerized period-amplitude analysis of sleep EEG was also performed. The schizophrenics showed marked reduction in the amount of slow-wave sleep (SWS) and in the number of delta half-waves during all-night sleep, especially those with higher amplitude, as compared to the normals. The number of delta half-waves in the patients was markedly reduced during the first sleep cycle. The average amplitude of delta half-waves during all-night sleep in the schizophrenics was significantly lower than that in the normals. The half-wave count of total delta waves in the schizophrenics was higher during treatment with ZPC than with BZDs, although no significant differences were observed in the amount of SWS between the two treatments. Soundness of sleep in the subjective sleep assessment was better evaluated during treatment with ZPC than BZDs. These results suggest that reduction of SWS in schizophrenia may be attributable mainly to the decrease in the number of delta waves with higher amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RP KAJIMURA, N (reprint author), NATL CTR HOSP MENTAL NERVOUS & MUSCULAR DISORDERS,NATL CTR NEUROL & PSYCHIAT,TOKYO,JAPAN. NR 34 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1995 VL 15 IS 3 BP 303 EP 312 DI 10.1016/0920-9964(94)00054-C PG 10 WC Psychiatry SC Psychiatry GA QX564 UT WOS:A1995QX56400010 PM 7632629 ER PT J AU OGNIBENE, FP AF OGNIBENE, FP TI NONSPECIFIC AND LYMPHOCYTIC INTERSTITIAL PNEUMONITIS IN HIV-INFECTED INDIVIDUALS SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; PRIMARY PULMONARY-HYPERTENSION; PNEUMOCYSTIS-CARINII; DISEASE; AIDS; CHILDREN; VIRUS; INFANTS RP OGNIBENE, FP (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,10 CTR DR,MSC-1662,BETHESDA,MD 20892, USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PD MAY PY 1995 VL 16 IS 3 BP 227 EP 230 DI 10.1055/s-2007-1009832 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RC334 UT WOS:A1995RC33400008 ER PT J AU MILLER, H ARAL, S AF MILLER, H ARAL, S TI UNITING RESEARCH COMMUNITIES TO IMPROVE STD RESEARCH - AN INTRODUCTION FROM THE CDC AND NIH SO SEXUALLY TRANSMITTED DISEASES LA English DT Editorial Material C1 CTR DIS CONTROL & PREVENT,NATL CTR PREVENT SERV,DIV STD HIV PREVENT,ATLANTA,GA 30341. RP MILLER, H (reprint author), NIAID,STD BRANCH,SOLAR BLDG,ROOM 3A26,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY-JUN PY 1995 VL 22 IS 3 BP 162 EP 163 DI 10.1097/00007435-199505000-00006 PG 2 WC Infectious Diseases SC Infectious Diseases GA QY967 UT WOS:A1995QY96700006 PM 7652659 ER PT J AU HAN, L HOFMANN, T CHIANG, Y ANDERSON, WF AF HAN, L HOFMANN, T CHIANG, Y ANDERSON, WF TI CHIMERIC ENVELOPE GLYCOPROTEINS CONSTRUCTED BETWEEN AMPHOTROPIC AND XENOTROPIC MURINE LEUKEMIA RETROVIRUSES SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID LONG TERMINAL REPEAT; HOST RANGE; GENE DETERMINE; ENV GENE; VIRUS; SEQUENCES; PROTEINS; REGION; RECOMBINATION AB A set of chimeric envelope proteins between amphotropic and xenotropic murine leukemia retroviruses (MuLV), two closely related members in the MuLV family, were constructed The purpose was to examine the regions that could be successfully enchanged between these two similar viral envelope proteins. The data indicate that fully active chimeras can be built when the junction is either at the EcoRI site (amino acid 169) 42 amino acids N-terminal to the polyproline hinge of gp70 (named CH4) or at the ScaI site (aa 593) in the membrane spanning portion of p15E (CH1). However, a chimera at the AflII site (aa 125, CH5) and two in the C-terminal end of gp70 (aa 418, CH2; aa 326, CH3) were inactive. These results, taken together with other data from our laboratory and others, suggest that the entire gp70/p15E structure is sensitive to alterations and that even envelope proteins that are very similar have only a limited ability to exchange sequences. C1 NIH,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. RP HAN, L (reprint author), GENET THERAPY INC,19 FIRSTFIELD RD,GAITHERSBURG,MD 20878, USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAY PY 1995 VL 21 IS 3 BP 205 EP 214 DI 10.1007/BF02254771 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TD750 UT WOS:A1995TD75000005 PM 7482034 ER PT J AU YOUNG, JB WEINER, DH YUSUF, S PRATT, CM KOSTIS, JB WEISS, MB SCHROEDER, E GUILLOTE, M AF YOUNG, JB WEINER, DH YUSUF, S PRATT, CM KOSTIS, JB WEISS, MB SCHROEDER, E GUILLOTE, M TI PATTERNS OF MEDICATION USE IN PATIENTS WITH HEART-FAILURE - A REPORT FROM THE REGISTRY OF STUDIES OF LEFT-VENTRICULAR DYSFUNCTION (SOLVD) SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID CALCIUM-CHANNEL BLOCKERS; MYOCARDIAL-INFARCTION; EJECTION FRACTION; CLINICAL-TRIALS; MORTALITY; THERAPY; INHIBITORS; ENALAPRIL; DIGOXIN; DRUGS AB To determine patterns of medication use based on clinical variables in patients with heart failure, we analyzed data from 5,999 patients participating in the Registry of Studies of Left Ventricular Dysfunction (SOLVD). The Registry comprised a broad spectrum of patients with heart failure, including some with predominantly diastolic dysfunction, Drug use was determined in a population cross-sectional manner at the time of identification (74% hospitalized), The median number of drugs per patient was four, with diuretics taken by 62%, digitalis by 45%, angiotensin-converting enzyme inhibitors (ACE-I) by 32%, calcium channel blockers by 36%, antiarrhythmics by 22%, and beta-blockers by 18%. Only 18% were on the combination of-ACE-I, diuretic, and digitalis, Stratification for diagnosis, heart failure symptoms, and ejection fractions demonstrated that triple-drug therapy (digitalis, diuretic, and ACE-I) was common only in those with ejection fractions less than .20 and several signs or symptoms of heart failure, Older patients were taking diuretics frequently (73% of patients older than 70 years of age), and our European center used fewer drugs overall, while prescribing digitalis about half as frequently as North American clinics. These data serve as the baseline for analysis of evolving therapeutic practice in patients with heart failure, C1 BAYLOR COLL MED, HOUSTON, TX 77030 USA. NHLBI, BETHESDA, MD 20892 USA. NEW YORK MED COLL, VALHALLA, NY 10595 USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. UNIV MED & DENT NEW JERSEY, NEW BRUNSWICK, NJ USA. UNIV LOUVAIN, BRUSSELS, BELGIUM. UNIV N CAROLINA, CHAPEL HILL, NC USA. NR 34 TC 45 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD MAY PY 1995 VL 88 IS 5 BP 514 EP 523 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QX244 UT WOS:A1995QX24400002 PM 7732439 ER PT J AU KEHRL, JH AF KEHRL, JH TI HEMATOPOIETIC LINEAGE COMMITMENT - ROLE OF TRANSCRIPTION FACTORS SO STEM CELLS LA English DT Review DE HEMATOPOIESIS; MYELOPOIESIS; LYMPHOPOIESIS; TRANSCRIPTION; LINEAGE; DIFFERENTIATION ID EMBRYONIC STEM-CELLS; ACTIVATED T-CELLS; IMMUNOGLOBULIN GENE-TRANSCRIPTION; CCAAT DISPLACEMENT PROTEIN; PU.1 REGULATES EXPRESSION; LEUCINE ZIPPER PROTEIN; ACUTE MYELOID-LEUKEMIA; DNA-BINDING PROTEINS; VIRUS ENHANCER CORE; ETS-RELATED PROTEIN AB This review focuses on the roles of transcription factors in hematopoietic lineage commitment. A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types. Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis, Finally, the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid, myeloid and lymphoid cell types is summarized. RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,B CELL MOLEC IMMUNOL SECT,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 169 TC 43 Z9 43 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 1995 VL 13 IS 3 BP 223 EP 241 PG 19 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA QX563 UT WOS:A1995QX56300003 PM 7613490 ER PT J AU HASHIMOTO, K SCHEFFEL, U LONDON, ED AF HASHIMOTO, K SCHEFFEL, U LONDON, ED TI IN-VIVO LABELING OF SIGMA-RECEPTORS IN MOUSE-BRAIN WITH [H-3] 4-PHENYL-1-(4-PHENYLBUTYL)PIPERIDINE SO SYNAPSE LA English DT Article DE BRAIN IMAGING; RECEPTOR BINDING; POSITRON EMISSION TOMOGRAPHY; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY ID BINDING-SITES; ANTIPSYCHOTIC DRUG; AFFINITY; INVIVO; LIGAND; HALOPERIDOL; PET AB 4-Phenyl-1-(4-phenylbutyl)piperidine (4-PPBP) is a very potent ligand for sigma (Sigma) receptors. The present study was undertaken to evaluate [H-3]4-PPBP as a radioligand for in vivo labeling of cerebral sigma receptors. After intravenous administration of [H-3]4-PPBP to mice, there is high uptake of radioactivity in the brain. The regional distribution of radioactivity in the brain 2 h after intravenous injection of [H-3]4-PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum greater than or equal to prefrontal cortex greater than or equal to parietal cortex > hypothalamus > olfactory tubercle greater than or equal to thalamus > hippocampus > striatum). Pretreatment with haloperidol(2 mg/ kg) significantly decreases the radioactivity measured in the brain 30-120 min after injection of [H-3]4-PPBP. Pretreatment with unlabeled 4-PPBP or ifenprodil also significantly decreases radioactivity in the brain 2 h after injection of [H-3]4-PPBP, in a dose-dependent manner. The in vivo binding of [H-3]4-PPBP in the brain also is significantly inhibited by SL 82.0715, BMY 14802, 1,3-di-o-tolylguanidine (DTG), and (+)-enantiomers of pentazocine, SKF 10,047, and 3-PPP, but not by the corresponding (-)-enantiomers, consistent with stereoselectivity of inhibition obtained in in vitro binding studies. In contrast, pretreatment with dizocilpine and spiperone does not inhibit in vivo binding of[H-3]4-PPBP. The results indicate that [H-3]4-PPBP would be a suitable radioligand for in vivo labeling of a receptors in brain. (C) 1995 Wiley-Liss, Inc. C1 NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD. JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. FU NINDS NIH HHS [NS 15080] NR 27 TC 18 Z9 19 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 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 1995 VL 20 IS 1 BP 85 EP 90 DI 10.1002/syn.890200112 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QV993 UT WOS:A1995QV99300011 PM 7624833 ER PT J AU WINKLER, JD HONG, BC KIM, S LEWIN, NE BLUMBERG, PM AF WINKLER, JD HONG, BC KIM, S LEWIN, NE BLUMBERG, PM TI ON THE PROTEIN-KINASE-C PHARMACOPHORE - SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 4-HYDROXYLATED ANALOGS OF INGENOL SO SYNLETT LA English DT Note DE INGENOL; PROTEIN KINASE C; PHARMACOPHORE; STRUCTURE-ACTIVITY RELATIONSHIPS ID PHORBOL ESTER PHARMACOPHORE; TUMOR PROMOTERS; RECEPTOR; FAMILY AB The synthesis and preliminary biological evaluation of the first C-4 hydroxylated analog of ingenol are described. The activity of 4 demonstrates that the C-4 hydroxyl group is not a critical component of the pharmacophore for protein kinase C binding and activation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. RP WINKLER, JD (reprint author), UNIV PENN,DEPT CHEM,PHILADELPHIA,PA 19104, USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD MAY PY 1995 IS 5 SI SI BP 533 EP 535 PG 3 WC Chemistry, Organic SC Chemistry GA RD261 UT WOS:A1995RD26100020 ER PT J AU DIXON, D HEIDER, K ELWELL, MR AF DIXON, D HEIDER, K ELWELL, MR TI INCIDENCE OF NONNEOPLASTIC LESIONS IN HISTORICAL CONTROL MALE AND FEMALE FISCHER-344 RATS FROM 90-DAY TOXICITY STUDIES SO TOXICOLOGIC PATHOLOGY LA English DT Article DE HISTOPATHOLOGY; NATIONAL TOXICOLOGY PROGRAM; PRECHRONIC; RODENTS; SPONTANEOUS AB The incidence of all spontaneously occurring histologic lesions was determined for control Fischer-344 (F-344) rats from 90-day (13-wk) prechronic National Toxicology Program (NTP) toxicity studies. A total of 319 rats, represented by control groups of 10 males and 10 females each from dosed feed (n = 8), inhalation (n = 4), and gavage (n = 4) studies were included in the review. All protocol required tissues routinely collected for evaluation were reexamined for potential nonneoplastic and neoplastic lesions. Histopathologic findings in tissues included a spectrum of degenerative and inflammatory lesions. The most common lesions in male rats were nephropathy [145/160 (90.6%)] and cardiomyopathy [125/158 (79.1%)]. These changes were also present in the female rats, however, at much lower incidence rates [nephropathy = 30/157 (19.1%); cardiomyopathy = 36/158 (22.8%)]. Other less frequently occurring lesions included inflammation of the preputial [36/152 (23.7%)] and clitoral [34/155 (21.9%)] glands and inflammation of the liver consisting of either foci of mononuclear inflammatory cells [19/159 (11.9%) in males and 33/159 (20.8%) in females] or focal granulomatous inflammation [1/159 (0.6%) in males and 14/159 (8.8%) in females] Pancreatic acinar cell atrophy occurred in both males [11/160 (6.9%)] and females [8/159 (5.0%)]. A variety of other less common nonneoplastic lesions were identified in both sexes of rats. Also recorded in this review are histologic changes generally considered to be components of the normal morphology of a particular tissue or organ for the F-344 rat (i.e., extramedullary hematopoiesis and hemosiderin deposition in the spleen, renal mineralization, uterine dilation, etc.). These findings were included and discussed due to potential treatment effects that may result in an increase or decrease in these changes compared to controls. Neoplasms were not observed in rats from the prechronic studies evaluated. RP DIXON, D (reprint author), NIEHS,EXPTL CARCINOGENESIS PROGRAM,POB 12233,MDC2-09,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 26 Z9 27 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1995 VL 23 IS 3 BP 338 EP 348 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA RD372 UT WOS:A1995RD37200010 PM 7659956 ER PT J AU DIWAN, BA ANDERSON, LM WARD, JM HENNEMAN, JR RICE, JM AF DIWAN, BA ANDERSON, LM WARD, JM HENNEMAN, JR RICE, JM TI TRANSPLACENTAL CARCINOGENESIS BY CISPLATIN IN F344/NCR RATS - PROMOTION OF KIDNEY TUMORS BY POSTNATAL ADMINISTRATION OF SODIUM BARBITAL SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CIS-DIAMMINEDICHLOROPLATINUM; DNA-ADDUCTS; CELLS; MOUSE; CIS-PLATINUM(II)DIAMMINEDICHLORIDE; EMBRYOTOXICITY; CHEMOTHERAPY; INITIATION; CARCINOMA; PREGNANCY AB Transplacental carcinogenic effects of cis-dichlorodiammineplatinum (cis-DDP) in F344 rats were investigated. Pregnant F344 rats were given a single ip administration of either cis-DDP (5 mg/kg body wt; group 1) or saline only (group 2) on Day 18 of gestation, Offspring of groups 1 and 2 were randomly and equally divided into two subgroups: 1a, 1b and 2a, 2b, respectively, Beginning at 4 weeks of age, offspring in groups 1b and 2b received 500 ppm of sodium barbital (NaBB) in diet, while those in groups 1a and 2a received normal diet. The experiment was terminated at 79 weeks of age. A low incidence (2/19; 10.5%) of male offspring exposed to transplacental cis-DDP (group 1a) developed renal cell adenomas, Postnatal administration of NaBB significantly enhanced this incidence (10/22; p < 0.01) in cis-DDP-initiated offspring. Also, multiple kidney tumors were more common in group 1b than any other group and three animals in this group developed frank renal cell carcinomas, cis-DDP, administered transplacentally, was a complete carcinogen for rat liver as the incidence of hepatocellular adenomas was significantly higher in offspring exposed transplacentally to cis-DDP than in those exposed to saline (20/82 vs 3/75; p < 0.05). NaBB, a known promoter of hepatocellular carcinogenesis in adult rats initiated with N-nitrosodiethylamine, failed to promote liver carcinogenesis initiated by transplacental cis-DDP. Tumors of the central nervous system (3/82; gliomas) and peripheral nervous system (2/82; schwannomas) were found only in offspring exposed transplacentally to cis-DDP. Thus, cis-DDP, administered transplacentally, was a strong initiator of renal cell tumors and a complete carcinogen for multiple organs in rat offspring. (C) 1995 Academic Press, Inc. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP DIWAN, BA (reprint author), PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 46 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1995 VL 132 IS 1 BP 115 EP 121 DI 10.1006/taap.1995.1092 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QY789 UT WOS:A1995QY78900013 PM 7747274 ER PT J AU COOGAN, TP SHIRAISHI, N WAALKES, MP AF COOGAN, TP SHIRAISHI, N WAALKES, MP TI MINIMAL BASAL ACTIVITY AND LACK OF METAL-INDUCED ACTIVATION OF THE METALLOTHIONEIN GENE CORRELATES WITH LOBE-SPECIFIC SENSITIVITY TO THE CARCINOGENIC EFFECTS OF CADMIUM IN THE RAT PROSTATE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; SPECIAL EMPHASIS; TUMOR-INDUCTION; INJECTION SITE; I GENE; ZINC; CANCER; CELLS; LOCALIZATION AB Metallothionein (MT), a high-affinity metal-binding protein, is known to detoxicate cadmium and may play an important role in cadmium carcinogenesis. In the rat, the ventral lobe of the prostate is sensitive to cadmium carcinogenesis, while the dorsolateral lobe is refractory, The possibility exists that the basis of this lobe-specific sensitivity may lie in the expression of the MT gene. Thus, the expression of the MT gene in lobes of the rat prostate was studied and, for comparative purposes, the expression of the MT gene in the liver, a tissue with well-defined high activity, was also assessed. MT gene expression was determined using a cDNA probe specific for MT-I, oligonucleotide probes specific for MT-I and MT-II, and an assay for cadmium-binding protein capacity. Basal levels of MT-I mRNA and cadmium-binding protein were much less in the ventral prostate than in the liver or dorsolateral prostate. Cadmium, given at a dose known to induce tumors of the ventral prostate (2.5 mu mol/kg, sc), did not result in an increase in MT gene expression in the ventral prostate, as assessed by cadmium-binding protein levels or MT-I mRNA, over 72 hr. Small elevations of cadmium-binding protein capacity were detected at high doses of cadmium (25 and 40 mu mol/kg) in the ventral prostate but no corresponding increases in MT mRNA were seen, In sharp contrast, hepatic MT gene expression was highly activated throughout the dosage range. Dose-response analysis 24 hr after cadmium administration (0.25 to 40 mu mol/kg, sc) showed that MT-I and MT-II mRNA levels were increased in liver in a dose-dependent manner, while no evidence was found for MT gene activation in ventral prostate, In the dorsolateral prostate the high basal activity of the MT gene was shown, as assessed by MT-I and MT-II mRNA levels, which was not further elevated by cadmium treatments. Cadmium accumulation was much lower in the ventral prostate than in the liver. However, levels of cadmium that were sufficient to activate the hepatic MT gene had, in fact, reached the ventral prostate. Thus, the poor basal expression and lack of activation of the MT gene within the ventral lobe of the rat prostate may be the genetic basis to this tissue's sensitivity to the carcinogenic effects of cadmium. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 62 TC 22 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1995 VL 132 IS 1 BP 164 EP 173 DI 10.1006/taap.1995.1097 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QY789 UT WOS:A1995QY78900018 PM 7747280 ER PT J AU ROTHMAN, N AF ROTHMAN, N TI GENETIC SUSCEPTIBILITY BIOMARKERS IN STUDIES OF OCCUPATIONAL AND ENVIRONMENTAL CANCER - METHODOLOGIC ISSUES SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT International Symposium on Human Health and Environment: Mechanisms of Toxicity and Biomarkers to Assess Adverse Effects of Chemicals CY SEP 25-30, 1994 CL SALSOMAGGIORE TERME, ITALY SP Int Commiss Occupat Hlth, Sci Comm Occupat Toxicol, European Commiss Hlth & Safety Directorate, Public Hlth Unit, Univ Parma, WHO, Int Agcy Res Canc, Int Programme Chem Safety, ILO UNEP WHO, Off Occupat Hlth, Reg Off Europe, Assoc Univ Italiana Med Lavoro Bernardino Ramazzini DE CANCER EPIDEMIOLOGY; BIOMARKERS; STUDY DESIGN; ENZYME POLYMORPHISM ID MISCLASSIFICATION; CARCINOGENESIS AB When using biomarkers to assess genetic susceptibility for cancer risk, the following issues should be recognized: (i) exposure assessment should receive as much attention as marker measurement; (ii) it is critical to study cases with a wide range of exposure patterns; (iii) each approach to evaluating susceptibility has its own potential biases; (iv) it is important to demonstrate the biologic plausibility of gene-exposure interactions detected in epidemiologic studies. RP ROTHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EPN 418,BETHESDA,MD 20892, USA. NR 24 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI PUBL 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 MAY PY 1995 VL 77 IS 1-3 BP 221 EP 225 DI 10.1016/0378-4274(95)03298-3 PG 5 WC Toxicology SC Toxicology GA RE273 UT WOS:A1995RE27300035 PM 7618141 ER PT J AU LEE, JH KLEIN, HG AF LEE, JH KLEIN, HG TI THE EFFECT OF DONOR RED-CELL SEDIMENTATION-RATE ON EFFICIENCY OF GRANULOCYTE COLLECTION BY CENTRIFUGAL LEUKAPHERESIS SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSFUSION THERAPY; TRIAL; LEUKEMIA; EFFICACY; BLOOD AB Background: Granulocyte collection relies on the use of a red cell-sedimenting agent and is influenced by poorly defined intrinsic donor characteristics. The donor's baseline red cell (erythrocyte) sedimentation rate (ESR), a readily measurable intrinsic donor variable, may influence the effectiveness of red cell-sedimenting agents and affect the granulocyte yield. Study Design and Methods: The in vitro and in vivo effects of 6-percent hydroxyethyl starch on the donor ESR were prospectively studied in 67 granulocytapheresis procedures with a blood cell separator, and the findings were correlated with granulocyte collection efficiency (GCE). A relationship that predicts the GCE on the basis of the donor ESR was then derived and tested. Results: The 3.7-fold mean increase in the donor ESR measured after in vitro addition of hydroxyethyl starch approximated the 3.3-fold increase measured when it was administered to the donors. Higher baseline ESR correlated with larger in vitro and in vivo hydroxyethyl starch-induced increases in ESR and predicted more efficient cell collections and greater cell yields, Furthermore, both ESR and GCE, which varied significantly among donors, remained constant for a given donor undergoing repeat procedures. The results could be summarized by a simple predictive formula that relates the GCE (%) to the ESR (mm/hour): GCE = 1.3ESR + 45. The GCE and yield as predicted by the formula were accurate within 10 percent of the observed values in six subsequent procedures. Conclusion: In granulocyte harvests using a blood cell separator with hydroxyethyl starch as the sedimenting agent, 1) both ESR and GCE vary widely among donors yet may remain relatively constant for a given donor; 2) the baseline ESR correlates with hydroxyethyl starch-modified ESR and with GCE; and 3) it may be possible to predict GCE and yield from the donor's baseline ESR. RP LEE, JH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1995 VL 35 IS 5 BP 384 EP 388 DI 10.1046/j.1537-2995.1995.35595259147.x PG 5 WC Hematology SC Hematology GA QX938 UT WOS:A1995QX93800005 PM 7740608 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - AGAROSE-GEL ELECTROPHORESIS IN YOUR KITCHEN SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1995 VL 20 IS 5 BP 202 EP 203 DI 10.1016/S0968-0004(00)89008-8 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QY879 UT WOS:A1995QY87900011 PM 7610485 ER PT J AU ROTH, GS JOSEPH, JA MASON, RP AF ROTH, GS JOSEPH, JA MASON, RP TI MEMBRANE-ALTERATIONS AS CAUSES OF IMPAIRED SIGNAL-TRANSDUCTION IN ALZHEIMERS-DISEASE AND AGING SO TRENDS IN NEUROSCIENCES LA English DT Article ID AMYLOID PRECURSOR PROTEIN; AFFINITY AGONIST BINDING; CULTURED SKIN FIBROBLASTS; POSTMORTEM HUMAN-BRAIN; ADENYLATE-CYCLASE; MUSCARINIC RECEPTORS; TRANSGENIC MICE; CORTICAL MEMBRANES; PARKINSONS-DISEASE; SENESCENT RATS AB Changes in cell-membrane composition in normal aging and in Alzheimer's and other age-related diseases appear to result in impaired neurotransmitter-triggered signal transduction. The impaired signal transduction seems to be related to dysfunctions in the coupling of G proteins to their receptors and effecters. Direct demonstration of altered physiochemical properties of brain tissue of patients with Alzheimer's disease has been achieved by small-angle X-ray diffraction. In this disease, thinner membranes correlate with a 30% decrease in moles of cholesterol: phospholipid. Such changes can affect directly the coupling and uncoupling properties of G proteins, and can account for signal transduction deficits. These findings offer a complementary alternative to the beta-amyloid hypothesis, and an opportunity to consider new types of therapeutic interventions. C1 TUFTS UNIV, USDA ARS, CTR HUMAN NUTR, BOSTON, MA 02111 USA. ALLEGHENY SINGER RES INST, NEUROSCI RES CTR, PITTSBURGH, PA 15212 USA. RP NIA, JOHNS HOPKINS BAYVIEW MED CTR, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA. NR 57 TC 145 Z9 146 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 EI 1878-108X J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1995 VL 18 IS 5 BP 203 EP 206 DI 10.1016/0166-2236(95)93902-A PG 4 WC Neurosciences SC Neurosciences & Neurology GA QV657 UT WOS:A1995QV65700001 PM 7610488 ER PT J AU USDIN, TB EIDEN, LE BONNER, TI ERICKSON, JD AF USDIN, TB EIDEN, LE BONNER, TI ERICKSON, JD TI MOLECULAR-BIOLOGY OF THE VESICULAR ACH TRANSPORTER SO TRENDS IN NEUROSCIENCES LA English DT Review ID CHOLINE-ACETYLTRANSFERASE GENE; NEMATODE CAENORHABDITIS-ELEGANS; TORPEDO ELECTRIC ORGAN; NERVE GROWTH-FACTOR; SYNAPTIC VESICLES; MONOAMINE TRANSPORTER; VESAMICOL RECEPTOR; PROMOTER REGION; ACETYLCHOLINE TRANSPORTER; CHROMAFFIN GRANULES AB The cholinergic synapse has long been a model for biochemical studies of neurotransmission. The molecules that are responsible for synaptic transmission are being identified rapidly. The vesicular transporter for ACh, which is responsible for the concentration of ACh within synaptic vesicles, has been characterized recently, both at the molecular and functional level. Definitive identification of the cloned gene involved genetics of Caenorhabditis elegans, the specialized Torpedo electromotor system, and expression in mammalian tissue culture. Comparison of the vesicular transporter for ACh with the vesicular transporters for monoamines demonstrates a new gene family. Gene mapping has demonstrated a unique relationship between the genes for the vesicular ACh transporter and for choline acetyltransferase. RP USDIN, TB (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 71 TC 128 Z9 128 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1995 VL 18 IS 5 BP 218 EP 224 DI 10.1016/0166-2236(95)93906-E PG 7 WC Neurosciences SC Neurosciences & Neurology GA QV657 UT WOS:A1995QV65700006 PM 7610492 ER PT J AU CADEDDU, JA PEARSON, JD LEE, BR LANDIS, P PARTIN, AW EPSTEIN, JI CARTER, HB AF CADEDDU, JA PEARSON, JD LEE, BR LANDIS, P PARTIN, AW EPSTEIN, JI CARTER, HB TI RELATIONSHIP BETWEEN CHANGES IN PROSTATE-SPECIFIC ANTIGEN AND THE PERCENT OF PROSTATIC EPITHELIUM IN MEN WITH BENIGN PROSTATIC HYPERPLASIA SO UROLOGY LA English DT Article ID SMOOTH-MUSCLE; AREA DENSITY; DISEASE; AGE AB Objectives. Pretreatment knowledge of prostate gland histology would allow a more scientifically based selection of medical therapy for men with benign prostatic hyperplasia (BPH) and may increase the effectiveness of the pharmacologic agents available. Changes in prostate-specific antigen (PSA), or PSA velocity, may reflect prostatic epithelial growth in BPH. Our objective was to determine if PSA velocity prior to diagnosis correlated with the relative amount of epithelium in BPH tissue. Methods. We evaluated 39 men with BPH who had serial PSA determinations (mean, 5.4) on frozen sera from 2.3 to 25.1 years before diagnosis, and archival material from simple prostatectomy available for pathologic evaluation. We used an immunoenzymatic staining technique for PSA to bind prostatic epithelium selectively so that color differences in the stained tissue sections could be used to quantify stroma, epithelium, and glandular lumina. Results. The average percentage of epithelium (%E) was 12.4 and the average stroma-epithelial ratio (SER) was 6.6. The correlation of PSA velocity for the three visits nearest to prostatectomy (n = 32) versus %E and SER was significant (P = 0.003 for both). The PSA value nearest to prostatectomy (n = 39) was directly correlated with %E and SER (P = 0.0001 and P = 0.001, respectively). Conclusions. These data suggest that PSA and PSA velocity are directly related to the histologic makeup of the prostate in men with BPH. Thus, pretreatment evaluation of PSA could be useful as part of an evaluation to direct BPH therapy. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT PATHOL,BALTIMORE,MD 21287. NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD 21224. NR 21 TC 12 Z9 13 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1995 VL 45 IS 5 BP 795 EP 800 DI 10.1016/S0090-4295(99)80086-7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA QW467 UT WOS:A1995QW46700017 PM 7538241 ER PT J AU SCHILLER, CA MONTALI, RJ DOI, S GROLLMAN, EF AF SCHILLER, CA MONTALI, RJ DOI, S GROLLMAN, EF TI CLINICAL AND MORPHOLOGIC FINDINGS OF FAMILIAL GOITER IN BONGO ANTELOPE (TRAGELAPHUS-EURYCERUS) SO VETERINARY PATHOLOGY LA English DT Article DE BONGO ANTELOPE; DEFECTIVE THYROGLOBULIN SYNTHESIS; FAMILIAL; GOITER; TRAGELAPHUS EURYCERUS ID THYROGLOBULIN SYNTHESIS DEFECT; HEREDITARY CONGENITAL GOITER; AFRIKANDER CATTLE; IODOPROTEIN PATTERN; GOATS; DEFICIENCY AB Inherited defects of thyroglobulin synthesis resulting in congenital goiter are well described in certain breeds of domestic ungulates and in human beings. Goiter associated with synthesis of an abnormal thyroglobulin and the presence of thyroidal albumin was identified in five closely related bongo antelopes (Tragelaphus eurycerus). The goiter had an adult onset, and the affected bongos appeared to remain euthyroid with normal serum T3 and T4 values, normal serum cholesterol concentrations, and nonelevated concentrations of circulating thyroid stimulating hormone (TSH). Goitrous bongos had significant reproductive difficulties, including reduced cyclic activity and prolonged gestations, but were otherwise normal. Over the course of the disease, the thyroid glands greatly enlarged (up to 10 x 20 cm) and became polycystic. Microscopically, there was an admixture of giant colloid-filled follicles and follicles of normal size lined with variable follicular epithelium ranging from squamoid to mildly to moderately hyperplastic. The pathogenesis of goiter in the bongo may reflect a mixture of genetic predisposition coupled with environmental factors, including a period of exposure to a goitrogen. C1 SMITHSONIAN INST,NATL ZOOL PK,DEPT PATHOL,WASHINGTON,DC 20008. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 22 TC 7 Z9 7 U1 1 U2 2 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAY PY 1995 VL 32 IS 3 BP 242 EP 249 PG 8 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA QX461 UT WOS:A1995QX46100005 PM 7604491 ER PT J AU ROBERTS, BJ KNIGHTS, KM AF ROBERTS, BJ KNIGHTS, KM TI DIFFERENTIAL INDUCTION OF RAT HEPATIC-MICROSOMAL AND PEROXISOMAL LONG-CHAIN AND NAFENOPIN-COA LIGASES BY CLOFIBRIC ACID AND DI-(2-ETHYLHEXYL)PHTHALATE SO XENOBIOTICA LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; COENZYME-A THIOESTERS; PROTEIN KINASE-C; ACYL-COENZYME; HYPOLIPEMIC DRUGS; LIVER PEROXISOMES; PALMITOYL-COA; SYNTHETASE; CIPROFIBRATE; HEPATOCYTES AB 1. Activity of rat hepatic microsomal and peroxisomal long-chain (palmitoyl) and nafenopin-CoA ligases were studied following administration of either clofibric acid, di-(2-ethylhexyl)phthalate (DEHP) or phenobarbitone. 2. Clofibric acid significantly induced the peroxisomal palmitoyl and nafenopin-Coa ligases, whilst no induction of the equivalent enzymes was observed in the microsomal fraction. 3. DEHP induced only palmitoyl-CoA formation in peroxisomes, whilst all enzymes were refractory to phenobarbitone treatment. 4. The enzyme-specific patterns of induction both intra- and inter-organelle suggest that the palmitoyl and nafenopin-CoA ligases are under different regulatory control. 5. Modulation of both the rate and extent of nafenopin-and palmitoyl-CoA formation was bath agent and organelle specific. 6. This study highlights the difficulty in delineating the individual roles of both fatty acyl-CoAs and xenobiotic-CoAs in peroxisome proliferation. C1 FLINDERS UNIV S AUSTRALIA,FAC HLTH SCI,SCH MED,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. NIAAA,BETHESDA,MD 20892. NR 39 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1995 VL 25 IS 5 BP 469 EP 476 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RD249 UT WOS:A1995RD24900004 PM 7571720 ER PT J AU ERKINE, AM SZENTGYORGYI, C SIMMONS, SF GROSS, DS AF ERKINE, AM SZENTGYORGYI, C SIMMONS, SF GROSS, DS TI THE UPSTREAM SEQUENCES OF THE HSP82 AND HSC82 GENES OF SACCHAROMYCES-CEREVISIAE - REGULATORY ELEMENTS AND NUCLEOSOME POSITIONING MOTIFS SO YEAST LA English DT Article DE HEAT SHOCK; PROMOTER; NUCLEOSOME POSITIONING; SACCHAROMYCES CEREVISIAE ID DNA-BINDING PROTEIN; HEAT-SHOCK FACTOR; CHROMATIN STRUCTURE; CRYSTAL-STRUCTURE; YEAST; TRANSCRIPTION; REGION; FAMILY; SITE; CIS AB We present the upstream sequences of HSP82 and HSC82, two closely related, but differentially regulated, heat-shock genes of Saccharomyces cerevisiae. Several dozen potential regulatory elements are identified within each upstream region; interestingly, only a few are conserved between the two genes. These include a consensus heat-shock element, an upstream repressor element, and a consensus TATA element. A search for motifs known actively to position nucleosomes in vitro revealed that such sequences are three- to seven-fold enriched within each promoter; a comparable enrichment is seen near the 3' end of each transcription unit. Located similar to 1100 bp upstream of HSC82 is an open reading frame (ORF) of 255 amino acids; similar to 800 bp upstream of HSP82 is an ORF of 132 amino acids. The latter ORF contains several conserved ankyrin motifs and appears to be expressed under normal growth conditions. Finally, we show by clamped homogeneous electric field gel electrophoresis that the two genetic loci map to different chromosomes: HSP82 to chromosome XVI and HSC82 to chromosome XIII. The sequences have been deposited in the GenBank database under Accession Numbers U20323 and U20349. C1 LOUISIANA STATE UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,SHREVEPORT,LA 71130. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM45842] NR 31 TC 7 Z9 8 U1 0 U2 1 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 MAY PY 1995 VL 11 IS 6 BP 573 EP 580 DI 10.1002/yea.320110607 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA QZ655 UT WOS:A1995QZ65500006 PM 7645348 ER PT J AU BYSTRICKY, S SZU, SC GOTOH, MG KOVAC, P AF BYSTRICKY, S SZU, SC GOTOH, MG KOVAC, P TI CIRCULAR-DICHROISM OF THE O-SPECIFIC POLYSACCHARIDE OF VIBRIO-CHOLERAE-01 AND SOME RELATED DERIVATIVES SO CARBOHYDRATE RESEARCH LA English DT Article DE O-SPECIFIC POLYSACCHARIDE; VIBRIO CHOLERAE ID IMMUNOLOGICAL PROPERTIES; LIPOPOLYSACCHARIDE; ANTIGEN AB The O-specific polysaccharide (O-SP) of Vibrio cholerae 01 is a homopolymer of alpha-(1-->2)-linked 4-amino-4,6-dideoxy-D-mannopyranose whose amino group is acylated with 3-deoxy-L-glycero-tetronic acid [N-(3-deoxy-L-glycero-tetronyl)-alpha-D-perosamine]. The circular dichroism (CD) of the O-SP as well as of a number of N-acyl (formyl, acetyl, 4-hydroxybutyl, 3-deoxy-L- and D-glycero-tetronyl) derivatives of methyl alpha-glycosides of 4-amino-4,6-dideoxy-D-mannopyranose (methyl alpha-D-perosaminide) has been studied for solutions in water, acetonitrile and 1,1,1-trifluoroethanol. The strong solvent dependence of the sign and intensity of the CD observed for the monosaccharide amides bearing achiral acyl groups is explained by solvent-mediated change of the orientation of the amido group relative to the proximal hydroxyl group at C-3. A change in the population of the nonplanar conformers with a pyramidal arrangement of bonds at the amido nitrogen has also been considered. The effect of solvents upon the CD spectra of compounds bearing chiral N-acyl substituents is less pronounced than that of their counterparts bearing achiral N-acyl substituents. The sign of the CD for the O-SP was found negative in all solvents used. This result is in agreement with the negative sign of the CD of the n --> pi* electron transition observed, independent of the solvent, for the monosaccharide derivative containing the L-glycero-3-deoxytetronamido group, and the positive sign found for its D-glycero-counterpart. C1 NIDDK,MED CHEM LAB,CARBOHYDRATES SECT,BETHESDA,MD 20892. RP BYSTRICKY, S (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 23 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 30 PY 1995 VL 270 IS 2 BP 115 EP 122 DI 10.1016/0008-6215(95)00017-N PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA RE581 UT WOS:A1995RE58100001 PM 7585695 ER PT J AU HENNINGFIELD, JE BENOWITZ, NL AF HENNINGFIELD, JE BENOWITZ, NL TI CIGARETTES AND ADDICTION SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 UNIV CALIF SAN FRANCISCO,DIV CLIN PHARMACOL & EXPTL THERAPEUT,SAN FRANCISCO,CA 94941. RP HENNINGFIELD, JE (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 10 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 APR 29 PY 1995 VL 310 IS 6987 BP 1082 EP 1083 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QW618 UT WOS:A1995QW61800002 PM 7742663 ER PT J AU PICKWORTH, WB AF PICKWORTH, WB TI CAFFEINE DEPENDENCE SO LANCET LA English DT Editorial Material ID DISCRIMINATION RP PICKWORTH, WB (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD APR 29 PY 1995 VL 345 IS 8957 BP 1066 EP 1066 DI 10.1016/S0140-6736(95)90814-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QV411 UT WOS:A1995QV41100006 PM 7715336 ER PT J AU PTITSYN, OB BYCHKOVA, VE UVERSKY, VN AF PTITSYN, OB BYCHKOVA, VE UVERSKY, VN TI KINETIC AND EQUILIBRIUM FOLDING INTERMEDIATES SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID MOLTEN-GLOBULE STATE; ALPHA-LACTALBUMIN; STAPHYLOCOCCUS-AUREUS; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; PROTEIN MOLECULES; COMPACT STATE; MECHANISM; DENATURATION; TRANSITIONS AB Our recent experiments on the molten globule state and other protein folding intermediates lead to following conclusions: (i) the molten globule is separated by intramolecular first-order phase transitions from the native and unfolded states and therefore is a specific thermodynamic state of protein molecules; (ii) the novel equilibrium folding intermediate (the 'pre-molten globule' state) exists which can be similar to the 'burst' kinetic intermediate of protein folding; (iii) proteins denature and release their non-polar ligands at moderately low pH and moderately low dielectric constant, i.e. under conditions which may be related to those near membranes. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP PTITSYN, OB (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 47 TC 84 Z9 85 U1 1 U2 7 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD APR 29 PY 1995 VL 348 IS 1323 BP 35 EP 41 DI 10.1098/rstb.1995.0043 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA QY315 UT WOS:A1995QY31500006 PM 7770484 ER PT J AU SOKOLOVA, IA COWAN, KH SCHNEIDER, E AF SOKOLOVA, IA COWAN, KH SCHNEIDER, E TI CA2+/MG2+-DEPENDENT ENDONUCLEASE ACTIVATION IS AN EARLY EVENT IN VP-16-INDUCED APOPTOSIS OF HUMAN BREAST-CANCER MCF7 CELLS IN-VITRO SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE ENDONUCLEASE; APOPTOSIS; DNA FRAGMENTATION ID CALCIUM-DEPENDENT ENDONUCLEASE; DNA FRAGMENTATION; INTERNUCLEOSOMAL FRAGMENTATION; ANTICANCER DRUGS; DEATH; CLEAVAGE; DEOXYRIBONUCLEASE; DEGRADATION; THYMOCYTES; ETOPOSIDE AB Apoptosis is now recognized as one of the major processes regulating the size of cell populations. However, despite intensive investigations the biochemical and enzymological mechanisms involved in apoptosis remain unclear. In the present study we demonstrate activation of a Ca2+/Mg2+-dependent endonuclease during VP-16-induced apoptosis in MCF7 cells. Nuclease activation occurred prior to the appearance of internucleosomal DNA fragmentation, suggesting that this activation may be an early and possibly critical step in drug-induced apoptosis. Analysis of the internucleosomal DNA fragments showed that they contained phosphorylated 5'-ends, indicating that they were produced by a Ca2+/Mg2+-dependent endonuclease. RP SOKOLOVA, IA (reprint author), NCI,MED BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 35 TC 33 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 28 PY 1995 VL 1266 IS 2 BP 135 EP 142 DI 10.1016/0167-4889(94)00233-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QW567 UT WOS:A1995QW56700004 PM 7742378 ER PT J AU SZALLASI, A BLUMBERG, PM LUNDBERG, JM AF SZALLASI, A BLUMBERG, PM LUNDBERG, JM TI PROTEIN-INHIBITION OF [H-3] RESINIFERATOXIN BINDING TO VANILLOID (CAPSAICIN) RECEPTORS IN RAT SPINAL-CORD SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE VANILLOID RECEPTOR; VANILNOID, ENDOGENOUS; RESINIFERATOXIN BINDING; CAPSAICIN; PROTON; POSITIVE COOPERATIVITY; NONCOMPETITIVE INHIBITION; DESENSITIZATION ID GENE-RELATED PEPTIDE; H-3 RESINIFERATOXIN BINDING; ROOT GANGLION NEURONS; LOW PH; SENSORY NERVES; SENSITIVE AFFERENTS; EFFERENT FUNCTION; URINARY-BLADDER; SOLEUS MUSCLE; CAPSAZEPINE AB Protons and capsaicin activate overlapping subsets of sensory nerves by opening ion conductances of similar properties. We have used the [H-3]resiniferatoxin binding assay utilizing rat spinal cord membranes to elucidate the possible interaction of protons at the vanilloid (capsaicin) receptor. Using low pH (pH 6.0 and pH 5.0) buffers, a time-dependent gradual decrease was observed in specific resiniferatoxin binding. Protons inhibited resiniferatoxin binding with an IC50 of pH 5.3 +/- 0.1. In experiments in which the concentration of [H-3]resiniferatoxin was varied, protons reduced the B-max value by approximately 40% with a corresponding 2-fold decrease in affinity. No change however, was observed in binding cooperativity (the Hill coefficients were 1.7 +/- 0.1 and 1.6 +/- 0.2 in the presence of pH 7.4 and pH 5.0 buffers, respectively). These changes in binding parameters are consistent with a non-competitive or, alternatively, mixed inhibitory mechanism. The remaining resiniferatoxin binding sites bound capsaicin with an affinity (K-i = 5.0 +/- 1.0 mu M) very similar to that determined in the presence of a pH 7.4 buffer (K-i = 3.0 +/- 1.5 mu M). A cyclooxygenase inhibitor, indomethacin (up to 10 mu M), did not prevent the action of protons on resiniferatoxin binding; neither was it mimicked by prostanoids (prostaglandin I-2 and E(1), both at 100 mu M). We conclude that protons interact at vanilloid receptors in the rat spinal cord; this interaction is either non-competitive or mixed in nature, and probably is not related to prostanoid generation. Protons and/or putative proton-generated mediators might represent endogenous modulators of the vanilloid receptor. C1 NCI,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RP SZALLASI, A (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,S-17177 STOCKHOLM,SWEDEN. NR 38 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD APR 28 PY 1995 VL 289 IS 2 BP 181 EP 187 DI 10.1016/0922-4106(95)90093-4 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QW561 UT WOS:A1995QW56100002 PM 7621890 ER PT J AU STANIMIROVIC, DB NIKODIJEVIC, B NIKODIJEVICKEDEVA, D MCCARRON, RM SPATZ, M AF STANIMIROVIC, DB NIKODIJEVIC, B NIKODIJEVICKEDEVA, D MCCARRON, RM SPATZ, M TI SIGNAL-TRANSDUCTION AND CA2+ UPTAKE ACTIVATED BY ENDOTHELINS IN RAT-BRAIN ENDOTHELIAL-CELLS (VOL 288, PG 1, 1994) SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Correction, Addition DE CEREBRAL ENDOTHELIUM; ENDOTHELIN; CA(2+) UPTAKE; SIGNAL TRANSDUCTION C1 NINCDS,STROKE BRANCH,BETHESDA,MD 20892. NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD APR 28 PY 1995 VL 289 IS 2 BP 409 EP 409 DI 10.1016/0922-4106(95)90123-X PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QW561 UT WOS:A1995QW56100032 ER PT J AU HUNYADY, L BOR, M BALLA, T CATT, KJ AF HUNYADY, L BOR, M BALLA, T CATT, KJ TI CRITICAL ROLE OF A CONSERVED INTRAMEMBRANE TYROSINE RESIDUE IN ANGIOTENSIN-II RECEPTOR ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ADRENAL GLOMERULOSA CELLS; PROTEIN-COUPLED RECEPTORS; BETA-ADRENERGIC-RECEPTOR; MUTAGENESIS; SIGNAL; SEQUESTRATION; GENERATION; LIGAND; GS AB The rat type 1a (AT(1a)) angiotensin II (Ang II) receptor contains a highly conserved tyrosine residue in the fifth transmembrane region that is present in most G protein-coupled receptors. The role of this amino acid in AT(1) receptor activation was analyzed in a mutant receptor (Y215F) created by replacing Tyr(215) with phenylalanine, The mutant receptor was highly expressed in transfected COS-7 cells, and its binding affinity for the peptide antagonist [Sar(1),Ile(8)]Ang II was similar to that of the wild type receptor. Although the structural integrity of the peptide ligand binding domain was preserved in the Y215F mutant receptor, its affinity for the native agonist, Ang II, was significantly reduced. Also, whereas guanosine 5'-3-O-(thio)triphosphate markedly reduced Ang II binding to the wild type receptor, it had little effect on agonist binding to the mutant receptor. Agonist-induced internalization of the mutant receptor was also impaired, and its ability to mediate inositoI phosphate responses to Ang II stimulation was abolished. The concomitant decreases in receptor internalization and G protein-mediated signaling of the Y215F mutant receptor indicate that Tyr(215) has a critical role in AT(1) receptor activation. In view of its conservation among members of the seven transmembrane domain receptor superfamily, this residue is likely to be of general importance in signal transduction from G protein-coupled receptors. C1 SEMMELWEIS UNIV MED,SCH MED,DEPT PHYSIOL,H-1444 BUDAPEST,HUNGARY. RP HUNYADY, L (reprint author), NICHHD,ERRB,BLDG 49,RM 6A36,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 27 TC 58 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 28 PY 1995 VL 270 IS 17 BP 9702 EP 9705 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700004 PM 7730346 ER PT J AU JAJU, M BEARD, WA WILSON, SH AF JAJU, M BEARD, WA WILSON, SH TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE - 3'-AZIDODEOXYTHYMIDINE 5'-TRIPHOSPHATE INHIBITION INDICATES 2-STEP BINDING FOR TEMPLATE-PRIMER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEADY-STATE KINETICS; 3'-AZIDO-3'-DEOXYTHYMIDINE 5'-TRIPHOSPHATE; THYMIDINE 5'-TRIPHOSPHATE; MECHANISM; PROCESSIVITY; MUTANT; LENGTH; REGION; ACID AB Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) catalyzes DNA synthesis by an ordered sequential mechanism, After template-primer (T . P) binds to free enzyme, the deoxynucleoside triphosphate to be incorporated binds to the RT and T . P binary complex (RT(T . P)). After incorporation of the bound nucleotide, catalytic cycling is limited either by a conformational change (for processive synthesis) or release of the enzyme from the extended T . P (for single-nucleotide incorporation), To explore cycling through these alternate rate-limiting steps, we determined kinetic parameters for single-nucleotide incorporation by HXB2R HIV-1 RT with chain-terminating nucleotide substrates 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and dideoxythymidine triphosphate on a homopolymeric T . P system, poly(rA)-oligo(dT)(16). Inhibition of processive deoxythymidine monophosphate in corporation by these chain-terminating substrates was also examined Because AZTTP is a substrate, its K-m should be equivalent to K-i, and since K-m for AZTTP should be influenced by the dissociation rate constant for RT(T . P), we examined the effect of altering RT(T .) P dissociation on AZTTP kinetic parameters, The dissociation rate constant was modulated by making use of different T . P substrates, viral sources of RT, and a mutant RT altered at a residue that perturbs T . P binding, As expected from earlier work, the time course of AZTMP incorporation on poly(rA)-oligo(dT)(16) was biphasic, with a burst followed by a slower steady-state phase representing k(cat) (0.42 min(-1)) which was similar to the rate constant for RT(T . P) dissociation. Additionally, K-m for AZTTP (110 nM) was lower than its equilibrium dissociation constant (1200 nM). AZTTP inhibition (K-i,K-AZTTP) of processive dTMP incorporation and incorporation of a single nucleotide were similar, However, a simple correlation between the RT(T . P) dissociation rate constant and K-i,K-AZTTP was not observed, These results indicate that a simple ordered model for single-nucleotide incorporation is inadequate and that different forms of RT(T . P) exist which can limit catalysis, The results are discussed in the context of a two-step binding reaction for T . P where the binary RT(T . P) complex undergoes an isomerization before binding of the deoxynucleotide substrate. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77555. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 30 TC 25 Z9 25 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 APR 28 PY 1995 VL 270 IS 17 BP 9740 EP 9747 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700010 PM 7537269 ER PT J AU CHALOVICH, JM CHEN, YD DUDEK, R LUO, H AF CHALOVICH, JM CHEN, YD DUDEK, R LUO, H TI KINETICS OF BINDING OF CALDESMON TO ACTIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; ACTOMYOSIN ATPASE ACTIVITY; CHICKEN GIZZARD CALDESMON; MYOSIN SUBFRAGMENT-1; SKELETAL-MUSCLE; THIN-FILAMENTS; TROPOMYOSIN; INHIBITION; CALMODULIN; DOMAIN AB The time course of interaction of caldesmon with actin may be monitored by fluorescence changes that occur upon the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or to acrylodan actin. The concentration dependence of the observed rate of caldesmon-actin binding was analyzed to a first approximation as a single-step reaction using a Monte Carlo simulation. The derived association and dissociation rates were 10(7) M(-1) S-1 and 18.2 S-1, respectively. Smooth muscle tropomyosin enhances the binding of caldesmon to actin, and this was found to be due to a reduction in the rate of dissociation to 6.3 S-1. There is no evidence from this study for a different mechanism of binding in the presence of tropomyosin. The floor escence changes that occurred with the binding of 12(N-methhyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or actin-tropomyosin were reversed by the addition of myosin subfragment 1 as predicted by a competitive binding mechanism. C1 E CAROLINA UNIV,SCH MED,DEPT ANAT,GREENVILLE,NC 27858. NIDDK,PHYS CHEM LAB,BETHESDA,MD 20892. 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 [R01 AR035216, AR35216, AR40540] NR 32 TC 11 Z9 11 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 APR 28 PY 1995 VL 270 IS 17 BP 9911 EP 9916 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700034 PM 7730374 ER PT J AU GOODNIGHT, J MISCHAK, H KOLCH, W MUSHINSKI, JF AF GOODNIGHT, J MISCHAK, H KOLCH, W MUSHINSKI, JF TI IMMUNOCYTOCHEMICAL LOCALIZATION OF 8 PROTEIN-KINASE-C ISOZYMES OVEREXPRESSED IN NIH 3T3 FIBROBLASTS - ISOFORM-SPECIFIC ASSOCIATION WITH MICROFILAMENTS, GOLGI, ENDOPLASMIC-RETICULUM, AND NUCLEAR AND CELL-MEMBRANES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL ESTER RECEPTOR; CYTOSKELETAL REARRANGEMENT; TRANSMEMBRANE PROTEINS; SUBSTRATE-SPECIFICITY; EMBRYO FIBROBLASTS; PLASMA-MEMBRANE; ACTIN FILAMENT; BETA-II; FAMILY; EXPRESSION AB We have used immunocytochemical analyses to characterize the subcellular distribution of protein kinase C (PKC)-alpha; -beta I, -beta II, -gamma, -delta, -epsilon, -xi, and -eta in NIH 3T3 fibroblasts that overexpress these different PKC isozymes. Immunofluorescence studies and Western blotting with antibodies specific for individual isoforms revealed that before activation the majority of the PKCs are not membrane-bound and are diffusely distributed throughout the cytoplasm. In addition, a fraction of PKC-delta and -eta appears membrane-bound and concentrated in the Golgi apparatus, Activation of each isozyme's kinase activity (with the exception of PKC-xi) by treatment of these cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in isozyme specific alterations of cell morphology, as well as in a rapid, selective redistribution of the different PKC isozymes to distinct subcellular structures, Within minutes after 12-O-tetradecanoylphorbol-13-acetate treatment, PKC-alpha and -epsilon concentrate at cell margins. In addition, PKC-alpha accumulates in the endoplasmic reticulum, PKC-beta II associates with actin-rich microfilaments of the cytoskeleton, PKC-gamma accumulates in Golgi organelles, and PKC-epsilon associates with nuclear membranes. Our results demonstrate that each activated PKC isozyme specifically associates with a particular cellular structure, presumably containing the substrate for that isozyme. These findings support the hypothesis that PKC substrate specificity in vivo is mediated, at least in part, by the restricted subcellular locale for each PKC isozyme and its target protein. C1 NCI, GENET LAB, MOLEC GENET SECT, BETHESDA, MD 20892 USA. GSF MUNICH, FORSCHUNGSZENTRUM HAMATOL, INST CLIN MOLEC BIOL & TUMOR GENET, D-81377 MUNICH, GERMANY. RI Mischak, Harald/E-8685-2011 NR 62 TC 279 Z9 279 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 28 PY 1995 VL 270 IS 17 BP 9991 EP 10001 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700045 PM 7730383 ER PT J AU ENGLANDER, EW HOWARD, BH AF ENGLANDER, EW HOWARD, BH TI NUCLEOSOME POSITIONING BY HUMAN ALU ELEMENTS IN CHROMATIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-III; REPEATED DNA-SEQUENCES; TUMOR VIRUS PROMOTER; MAMMALIAN GENOMES; TRANSGENIC MICE; XENOPUS-LAEVIS; GLOBIN GENES; TRANSCRIPTION; FAMILY; ORGANIZATION AB Alu sequences are interspersed throughout the genomes of primate cells, occurring singly and in clusters around RNA polymerase II-transcribed genes, Because these repeat elements are capable of positioning nucleosomes in in vitro reconstitutes (Englander, E. W., Wolffe, A. P., and Howard, B. H. (1993) J. Biol. Chem. 268, 19565-19573), we investigated whether they also influence in vivo chromatin structure. When assayed collectively using consensus sequence probes and native chromatin as template, Alu family members were found to confer rotational positioning on nucleosomes or nucleosome-like particles. In particular, a 10-base pair pattern of DNase I nicking that spanned the RNA polymerase III box A promoter motif extended upstream to cover diverse 5'-flanking sequences, suggesting that Alu repeats may in fluence patterns of nucleosome formation over neighboring regions. Computational analysis of a set of naturally occurring Alu sequences indicated that nucleosome positioning information is intrinsic to these elements, Inasmuch as local chromatin organization influences gene expression, the capacity of Alu sequences to affect chromatin structure as demonstrated here may help to clarify some features of these elements. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NR 63 TC 80 Z9 80 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 28 PY 1995 VL 270 IS 17 BP 10091 EP 10096 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700058 PM 7730313 ER PT J AU DOBI, A DAMERON, CT HU, S HAMER, D WINGE, DR AF DOBI, A DAMERON, CT HU, S HAMER, D WINGE, DR TI DISTINCT REGIONS OF CU(I)-CENTER-DOT-ACE1 CONTACT 2 SPATIALLY-RESOLVED DNA MAJOR GROOVE SITES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ECO RI ENDONUCLEASE; CUP2 GENE-PRODUCT; YEAST METALLOTHIONEIN; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; SUPEROXIDE-DISMUTASE; BINDING PROTEIN; EXPRESSION; COPPER; ACE1 AB The interaction between the Cu(I). ACE1 (CuACE1) transcription factor and its DNA binding site in the yeast metallothionein gene was studied by systematically altering the DNA sequence through base substitution, modification, and deletions as well as by altering the protein structure through chemical modification. We show here that CuACE1 is comprised of two distinct domains that contact DNA through minor groove interactions located between two major groove interaction sites. The minor groove interactions are shown to be critical for formation of a stable CuACE1 . DNA complex, The NH2-terminal segment of ACEI is shown to contact the 5'-most distal major groove site. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV UTAH,HLTH SCI CTR,SALT LAKE CITY,UT 84132. NR 34 TC 30 Z9 30 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 APR 28 PY 1995 VL 270 IS 17 BP 10171 EP 10178 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700067 PM 7730320 ER PT J AU HSU, K CHANG, DY MARAIA, RJ AF HSU, K CHANG, DY MARAIA, RJ TI HUMAN SIGNAL RECOGNITION PARTICLE (SRP) ALU-ASSOCIATED PROTEIN ALSO BINDS ALU INTERSPERSED REPEAT SEQUENCE RNAS - CHARACTERIZATION OF HUMAN SRP9 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 7SL RNA; SECONDARY STRUCTURE; MESSENGER-RNA; REPETITIVE SEQUENCES; 7SL-RNA COMPONENT; CYTOPLASMIC RNAS; HUMAN GENOME; GENE; EXPRESSION; ELEMENTS AB Nearly 1 million interspersed Alu elements reside in the human genome. Alu retrotransposition is presumably mediated by full-length Alu transcripts synthesized by RNA polymerase III, while some polymerase III-synthesized Alu transcripts undergo 3'-processing and accumulate as small cytoplasmic (sc) RNAs of unknown function. Interspersed Alu sequences also reside in the untranslated regions of some mRNAs. The Alu sequence is related to a portion of the 7SL RNA component of signal recognition particle (SRP), This region of 7SL RNA together with 9- and 14-kDa polypeptides (SRP9/14) regulates translational elongation of ribosomes engaged by SRP. Here we characterize human (h) SRP9 and show that it, together with hSRP14 (SRP9/14), forms the activity previously identified as Alu RNA-binding protein (REP), The primate-specific C-terminal tail of hSRP14 does not appreciably affect binding to scAlu RNA. K-d values for three Alu-homologous scRNAs were determined using Alu REP (SRP9/14) purified from HeLa cells. The Alu region of 7SL, scAlu, and scB1 RNAs exhibited K-d values of 203 pM, 318 pM, and 1.8 nM, respectively, Finally, Alu REP can bind with high affinity to synthetic mRNAs that contain interspersed Alus in their untranslated regions. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,HHMI,BETHESDA,MD 20817. NR 63 TC 43 Z9 44 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 APR 28 PY 1995 VL 270 IS 17 BP 10179 EP 10186 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700068 PM 7730321 ER PT J AU SATO, T XIAO, DM LI, H HUANG, FL HUANG, KP AF SATO, T XIAO, DM LI, H HUANG, FL HUANG, KP TI STRUCTURE AND REGULATION OF THE GENE ENCODING THE NEURON-SPECIFIC PROTEIN-KINASE-C SUBSTRATE NEUROGRANIN (RC3 PROTEIN) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPSIN-I GENE; CALMODULIN-BINDING DOMAIN; TYROSINE-HYDROXYLASE GENE; TRANSCRIPTION FACTOR AP-2; INTESTINAL-PEPTIDE GENE; BRAIN-SPECIFIC GENE; CYCLIC-AMP; PHOSPHORYLATION SITE; 5'-FLANKING REGION; ENHANCER ACTIVITY AB A 13-kilobase pair genomic DNA encoding a 78-amino acid brain-specific calmodulin-binding protein kinase C (PKC) substrate, neurogranin (Ng/RC3; also known as RC3 or p17), has been sequenced, The Ng/RC3 gene is composed of four exons and three introns, with the protein-coding region located in the first and second exons. This gene was found to have multiple transcriptional start sites clustered within 20 base pairs (bp); it lacks the TATA, GC, and CCAAT boxes in the proximal up stream region of the start sites. The promoter activity was characterized by transfection of 293 cells with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene. A minimal construct containing bp +11 to +256 was nearly as active as that covering bp -1508 to +256, whereas a shorter one covering bp +40 to +256 had a greatly reduced activity. Between bp +11 and +40 lies a 12-nucleotide sequence (CCCCGCCCGACCC) containing overlapping binding sites for AP2 (CCGCCCACCC) and SP1 (CCCGCC); this region may be important for conferring the basal transcriptional activity of the Ng/BC3 gene. The expression of a Ng/RC3-luciferase fusion construct (-1508/+256) in transfected 293 cells was stimulated by phorbol 12-myristate 13-acetate (PMA), but not by cAMP, arachidonic acid, vitamin D, retinoic acid, or thyroxines T-3 and T-4. PMA caused a 2-4-fold stimulation of all the reporter gene constructs ranging from +11/+256 to -1508/+256. The stimulatory effects of PMA could be magnified by cotransfection with both Ca2+-dependent and -independent phorbol ester-binding PKC-alpha, -beta(I), -beta(II), -gamma, -delta, and -epsilon cDNAs, but not by non-phorbol ester-binding PHC-xi cDNA. The Ng/RC3 and PKC-gamma genes have a similar expression pattern in the brain during development. These two genes share at least four conserved sequence segments 1.5 kiIobase pair upstream from their transcriptional start sites and a gross similarity in that they possess several AT-rich segments within bp -550 to -950, A near homogeneous 20-kDa DNA-binding protein purified from rat brain was able to bind to these AT-rich regions of both Ng/RC3 and PKC-gamma genes with footprints containing ATTA, ATAA, and AATA sequences. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,METAB REGULAT SECT,BETHESDA,MD 20892. NR 62 TC 34 Z9 37 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 APR 28 PY 1995 VL 270 IS 17 BP 10314 EP 10322 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700086 PM 7730337 ER PT J AU WIRTH, PJ ROMANO, A AF WIRTH, PJ ROMANO, A TI STAINING METHODS IN GEL-ELECTROPHORESIS, INCLUDING THE USE OF MULTIPLE DETECTION METHODS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review ID SULFATE-POLYACRYLAMIDE GELS; POLYVINYLIDENE DIFLUORIDE MEMBRANES; FLUORESCAMINE-LABELED PROTEINS; CEREBROSPINAL-FLUID PROTEINS; SENSITIVE SILVER STAIN; COMBINED ALCIAN BLUE; BINDING PROTEINS; COOMASSIE BLUE; NITROCELLULOSE MEMBRANES; MOLECULAR-WEIGHT AB Polyacrylamide gel electrophoresis is a reliable and widely used technique for the separation, identification and characterization of proteins and protein mixtures. With the introduction of high resolution two-dimensional polyacrylamide gel electrophoresis in 1975 upward to 2000 individual polypeptides spots are easily separated on a single electrophoretic gel thereby necessitating the availability of highly sensitive protein detection methods. Although a plethora of protein-staining and -visualization protocols have been described utilizing both radioactive and non-radioactive reagents, many times the use of mono-dimensional detection procedures is insufficient to address the experimental questions asked. The present review highlights the utilization of combined protein-labeling and -staining methodologies in gel electrophoresis including selected applications in polyacrylamide gels and solid membrane matrixes. RP NCI, EXPTL CARCINOGENESIS LAB, BIOPOLYMER CHEM SECT, BLDG 37, ROOM 3C28, BETHESDA, MD 20892 USA. NR 163 TC 61 Z9 63 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 28 PY 1995 VL 698 IS 1-2 BP 123 EP 143 DI 10.1016/0021-9673(94)00879-E PG 21 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QX155 UT WOS:A1995QX15500008 PM 7539685 ER PT J AU KLEPARNIK, K GARNER, M BOCEK, P AF KLEPARNIK, K GARNER, M BOCEK, P TI INJECTION BIAS OF DNA FRAGMENTS IN CAPILLARY ELECTROPHORESIS WITH SIEVING SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article AB The relative amounts of DNA fragments in a mixture injected into the capillary by electromigration or hydrodynamically by pressure were compared. Even if the electrophoretic mobilities of DNA fragments with different sizes are the same in a free solution in the sample vial, the size bias is brought about by the different mobilities in a sieving medium and by the electroosmosis. The experiments were performed in capillaries filled with a solution of liquified;agarose, a replaceable sieving medium. The experimental results were compared with a theoretical model. C1 ACAD SCI CZECH REPUBL,INST ANALYT CHEM,CR-61142 BRNO,CZECH REPUBLIC. NIH,PHYS & THEORET BIOL LAB,BETHESDA,MD 20892. RI Bocek, Petr/G-6821-2014 NR 13 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 28 PY 1995 VL 698 IS 1-2 BP 375 EP 383 DI 10.1016/0021-9673(94)00845-Z PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QX155 UT WOS:A1995QX15500023 PM 7773369 ER PT J AU BERTHA, CM FLIPPENANDERSON, JL ROTHMAN, RB PORRECA, F DAVIS, P XU, H BECKETTS, K CHA, XY RICE, KC AF BERTHA, CM FLIPPENANDERSON, JL ROTHMAN, RB PORRECA, F DAVIS, P XU, H BECKETTS, K CHA, XY RICE, KC TI PROBES FOR NARCOTIC RECEPTOR-MEDIATED PHENOMENA .20. ALTERATION OF OPIOID RECEPTOR SUBTYPE SELECTIVITY OF THE 5-(3-HYDROXYPHENYL)MORPHANS BY APPLICATION OF THE MESSAGE-ADDRESS CONCEPT - PREPARATION OF DELTA-OPIOID RECEPTOR LIGANDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; INDUCED STIMULATION; BINDING-SITES; CLONING; ANTAGONIST; ANTINOCICEPTION; MODULATION; DEPENDENCE; TOLERANCE AB Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized containing additional aromatic moieties, as an application of the message-address concept targeted at producing delta-opioid receptor selective ligands. In vitro radioreceptor binding studies in rat brain revealed that both of the parent enantiomers, (-)- and (+)-1, had a high affinity for the mu-opioid receptor (21 nM), a slight affinity for kappa(1)-opioid receptors (similar to 800-900 nM), and less than 1000 nM affinity for the delta-opioid receptor (mu/delta IC50 ratio of (0.02 for both). A derivative of(-)-1 containing an indole moiety fused at the C6-C7 position of the phenylmorphan nucleus, (-)-11, displayed a > 180-fold increase in affinity for the delta-opioid receptor with an IC50 value of 6 nM. The parent compound (-)-1 had only 26% agonist activity at 30 mu M in the mouse vas deferens (delta) bioassay, whereas compound (-)-11 had an IC50 Of 393 nM in this preparation, indicating the importance of the indole moiety in imparting delta-opioid agonist activity to the phenylmorphan (-)-11. A structure-activity relationship (SAR) study of N-alkyl derivatives of the racemic nor 11 indicated similarities between the interaction of various derivatives with the mu- and delta- but not the kappa(1)-opioid receptor. As studies on the molecular basis of the interaction of opioid ligands with their respective receptors continue to gain momentum, the SAR data described herein for the synthetic phenylmorphans will prove useful for further studies. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. NR 55 TC 12 Z9 12 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 28 PY 1995 VL 38 IS 9 BP 1523 EP 1537 DI 10.1021/jm00009a013 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QV560 UT WOS:A1995QV56000013 PM 7739011 ER PT J AU BRINE, GA STARK, PA LIU, Y CARROLL, FI SINGH, P XU, H ROTHMAN, RB AF BRINE, GA STARK, PA LIU, Y CARROLL, FI SINGH, P XU, H ROTHMAN, RB TI ENANTIOMERS OF DIASTEREOMERIC CIS-N-[1-(2-HYDROXY-2-PHENYLETHYL)-3-METHYL-4-PIPERIDYL]-N-PHENYLPROPANA MIDES - SYNTHESIS, X-RAY-ANALYSIS, AND BIOLOGICAL-ACTIVITIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID OPIOID BINDING-SITES; RECEPTOR-BINDING; POTENT ANALGESICS; OPIATE RECEPTOR; ANTAGONIST; ANALOGS; (+/-)-CIS-N-<1-(2-HYDROXY-2-PHENYLETHYL)-3-METHYL-4-PIPERIDYL>-N-PHENYLP ROPANAM.; (+)-CIS-3-METHYLFENTANYL; OHMEFENTANYL; SELECTIVITY AB (+/-)-cis-N-[1-(2-Hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (1) is a mixture of four stereoisomers [(2S,3R,4S)-1a, (2R,3R,4S)-1b, (2R,3S,4R)-1c, and(2S,3S,4R)-1d], which together constitute two diastereoisomeric pairs of optical isomers. These four stereoisomers were prepared from optically active intermediates of known absolute configuration by procedures which had no effect on the configurations of the piperidine 3- and 4-carbons. The configuration of the phenylethyl 2-carbon in the final products was determined by X-ray analysis of (2S,3S,4R)-1d. A H-1 NMR comparison of the final products to ohmefentanyl established that the racemic pair previously known as ohmefentanyl was a mixture of (2S,3R,4S)-1a and (2R,3S,4R)-1c. The individual activities of 1a, 1b, 1c, and 1d were evaluated in a variety of binding and pharmacological assays. The binding data revealed that isomers 1b and 1c had the highest affinity and selectivity for the mu site labeled with [H-3]DAMGO. In contrast, the four isomers displaced [H-3]etorphine in the order 1a approximate to 1b > 1c approximate to 1d. Evaluation of the four isomers on the mouse vas deferens (MVD) preparation revealed a potency order of 1a > 1b > 1c > 1d with concentrations of 1a and 1b in the femtomolar range causing inhibition. Experiments using the antagonists naltrexone (mu), ICI 174864 (delta), and norbinaltorphimine (kappa) demonstrated that the effects of 1a were mediated largely by the mu receptor while both delta and kappa agonist effects contributed to the actions of 1b and 1c. Isomer 1d acted as a weak mu antagonist in the MVD preparation. The same potency order was observed in a mouse analgesic assay and a rhesus monkey single dose suppression study. From the latter study the potency of 1a was estimated to be 20 000-50 000 times that of morphine, making this isomer one of the most potent opiates known. In the rhesus monkey study, isomer 1d failed to substitute for morphine and seemed to exacerbate withdrawal at doses of 0.6, 3.0, and 6.0 mg/kg. On the basis of the mouse data, isomer 1a was 21 000 times more potent than 1d, whereas isomers 1b and 1c were similar in their opiate activity in vivo. Using the optical isomers of cis-3-methylfentanyl as reference compounds, we analyzed the effects on the pharmacological activities of introducing a phenylethyl 2-hydroxyl group into the molecule. From this analysis we drew the following conclusions regarding structure: (a) the (3R,4S)-piperidine stereochemistry found in the more potent cis-3-methylfentanyl isomer was required for potent opiate agonist activity; (b) the introduction of a phenylethyl 2-hydroxyl with the S configuration had an enormous impact on this activity as demonstrated by the extraordinary mu agonist properties of 1a and the weak mu agonist/antagonist properties of 1d; and (c) the introduction of a 2-hydroxyl with the R configuration had a much smaller impact on the opiate agonist activity. Finally, our findings demonstrated the importance of the combination of 2-hydroxyl and 3-methyl substituents to the pharmacological properties of the four isomers. C1 N CAROLINA STATE UNIV,DEPT CHEM,RALEIGH,NC 27695. NIDA,IRP,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. RP BRINE, GA (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIDA NIH HHS [DA06317] NR 39 TC 29 Z9 29 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 28 PY 1995 VL 38 IS 9 BP 1547 EP 1557 DI 10.1021/jm00009a015 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QV560 UT WOS:A1995QV56000015 PM 7739013 ER PT J AU FISCHER, D LIN, SL WOLFSON, HL NUSSINOV, R AF FISCHER, D LIN, SL WOLFSON, HL NUSSINOV, R TI A GEOMETRY-BASED SUITE OF MOLECULAR DOCKING PROCESSES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE MOLECULAR DOCKING; DOCKING OF BOUND AND UNBOUND COMPLEXES; PROTEIN PROTEIN DOCKING; PROTEIN DRUG DOCKING; MOLECULAR SURFACE MATCHING ID RECOGNITION; SIMULATION; PROTEINS AB We have developed a geometry-based suite of processes for molecular docking. The suite consists of a molecular surface representation, a docking algorithm, and a surface inter-penetration and contact filter. The surface representation is composed of a sparse set of critical points (with their associated normals) positioned at the face centers of the molecular surface, providing a concise yet representative set. The docking algorithm is based on the Geometric Hashing technique, which indexes the critical points with their normals in a transformation invariant fashion preserving the multi-element geometric constraints. The inter-penetration and surface contact filter features a three-layer scoring system, through which docked models with high contact area and low clashes are funneled. This suite of processes enables a pipelined operation of molecular docking with high efficacy. Accurate and fast docking has been achieved with a rich collection of complexes and unbound molecules, including protein-protein and protein-small molecule associations. An energy evaluation routine assesses the intermolecular interactions of the funneled models obtained from the docking of the bound molecules by pairwise van der Waals and Coulombic potentials. Applications of this routine demonstrate the goodness of the high scoring, geometrically docked conformations of the bound crystal complexes. C1 TEL AVIV UNIV,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. 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. FU NCI NIH HHS [I-CO-74102] NR 25 TC 144 Z9 147 U1 1 U2 5 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 28 PY 1995 VL 248 IS 2 BP 459 EP 477 DI 10.1006/jmbi.1995.0234 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV413 UT WOS:A1995QV41300022 PM 7739053 ER PT J AU DICKSTEIN, BM WOSIKOWSKI, K BATES, SE AF DICKSTEIN, BM WOSIKOWSKI, K BATES, SE TI INCREASED RESISTANCE TO CYTOTOXIC AGENTS IN ZR75B HUMAN BREAST-CANCER CELLS TRANSFECTED WITH EPIDERMAL GROWTH-FACTOR RECEPTOR SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE EPIDERMAL GROWTH FACTOR RECEPTOR; MULTIDRUG RESISTANCE; HUMAN BREAST CANCER CELLS ID EXPRESSION; KINASE; LINE AB Human breast cancer cells selected for multidrug resistance frequently overexpress ligands and receptors in the epidermal growth factor (EGF) receptor family. To determine whether this overexpression contributes to the drug resistant phenotype, EGF receptor transfected ZR75B human breast cancer cells were examined. Two EGF receptor overexpressing clones were evaluated: clone 11 with >1 x 10(6) sites, and clone 13 with 310 000 receptor sites/cell. These were compared with clone 2-neo, which was transfected with the neomycin gene only and contained 43 000 receptor sites/cell. The EGF receptor overexpressing clones and the neo transfected control clone displayed comparable growth rates. Cytotoxicity analyses were performed with doxorubicin, vinblastine, cisplatin and 5-fluorouracil to determine the sensitivity of the clones to antineoplastic drugs. The EGF receptor overexpressing clones were found to be 1.5-5.6 times more resistant to the four drugs tested. This increase in the IC50 conferred a selective advantage when grown in the presence of 2, 3 and 6 ng/ml doxorubicin. Clone 13 cells overtook a mixed population which began with clone 2-neo comprising 95% of the cells. Clone 2-neo remained the dominant clone in the absence of drug. Finally, after long-term selection of the clones with 6 ng/ml doxorubicin, clone 2-neo became fourfold more resistant than the unselected clone 2-neo, a level which was comparable to that found in the EGF receptor overexpressing clones 11 and 13. No additional increase in resistance was observed for these clones, suggesting that clone 2-neo had developed additional resistance mechanisms. These results support the hypothesis that the EGF receptor pathway is able to confer a selective advantage to cells during drug exposure and potentially participates in the multidrug resistant phenotype. C1 NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. NR 24 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 28 PY 1995 VL 110 IS 1-2 BP 205 EP 211 DI 10.1016/0303-7207(95)03535-F PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA QZ088 UT WOS:A1995QZ08800024 PM 7672450 ER PT J AU JIMENEZASENSIO, J GONZALEZ, P ZIGLER, JS GARLAND, DL AF JIMENEZASENSIO, J GONZALEZ, P ZIGLER, JS GARLAND, DL TI GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IS AN ENZYME-CRYSTALLIN IN DIURNAL GECKOS OF THE GENUS PHELSUMA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID STRUCTURAL PROTEINS; LENS CRYSTALLINS; EYE LENS; RECRUITMENT; TISSUES AB Lenses from diurnal geckos, Phelsuma barbouri, Phelsuma madagascariensis grandis and Phelsuma serraticauda contain a prominent 37 kDa polypeptide (pi-crystallin) that is not present in lenses from the nocturnal geckos, Gekko gekko, Hemidactylus garnoti, Tarentola annularis, and Uroplatus henkeli. This protein was partially purified from P. serraticauda and was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPD). The GAPDs, which constitute 14-24% of the lens soluble protein in the diurnal species, were highly active. The presence of this enzyme in the lenses of diurnal, but not nocturnal, geckos supports the hypothesis that the oxido-reductases found as enzyme-crystallins may function in providing protection against the increased oxidative stress to which diurnal species are exposed. These findings strongly support the concept that the recruitment of enzyme-crystallins is a selective response to changes in the visual environment. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NR 20 TC 16 Z9 16 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 26 PY 1995 VL 209 IS 3 BP 796 EP 802 DI 10.1006/bbrc.1995.1570 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV602 UT WOS:A1995QV60200003 PM 7733971 ER PT J AU KOLE, HK AKAMATSU, M YE, B YAN, XJ BARFORD, D ROLLER, PP BURKE, TR AF KOLE, HK AKAMATSU, M YE, B YAN, XJ BARFORD, D ROLLER, PP BURKE, TR TI PROTEIN-TYROSINE-PHOSPHATASE INHIBITION BY A PEPTIDE-CONTAINING THE PHOSPHOTYROSYL MIMETIC, L-O-MALONYLTYROSINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SOLID-PHASE SYNTHESIS; SIGNAL TRANSDUCTION; ACTIVATION; DEPHOSPHORYLATION; PHOSPHORYLATION; DERIVATIVES; STABILITY; ANALOGS AB Peptides containing phosphonate based non-hydrolyzable phosphotyrosyl (pTyr) mimetics previously have been shown to be competitive inhibitors of protein-tyrosine phosphatases (PTPs). These agents suffer from low cellular penetration which is partially attributable to ionization of the phosphonate group at physiological pH. We have developed the non-phosphorus containing pTyr mimetic, L-O-malonyltyrosine (L-OMT) and herein demonstrate using a PTP 1B enzyme assay that it is superior to phosphonomethyl phenylalanine (Pmp) as a pTyr mimetic when incorporated into the hexamer peptide Ac-D-A-D-E-X-L-amide (X = D,L-Pmp, IC50 = 200 mu M; X = L-OMT, IC50 = 10 mu M). Prodrug protection of L-OMT as its carboxylic acid diester could potentially increase cellular penetration, thereby making this a valuable reagent for cellular studies. (C) 1995 Academic Press, Inc. C1 NCI,DCT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,DIABET UNIT,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. UNIV OXFORD,MOLEC BIOPHYS LAB,OXFORD OX1 3QU,ENGLAND. RI Burke, Terrence/N-2601-2014 NR 36 TC 70 Z9 72 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 26 PY 1995 VL 209 IS 3 BP 817 EP 822 DI 10.1006/bbrc.1995.1573 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV602 UT WOS:A1995QV60200006 PM 7537500 ER PT J AU CHUANG, LF CHUANG, TK KILLAM, KF QUI, Q WANG, XR LIN, JJ KUNG, HF SHENG, W CHAO, C YU, L CHUANG, RY AF CHUANG, LF CHUANG, TK KILLAM, KF QUI, Q WANG, XR LIN, JJ KUNG, HF SHENG, W CHAO, C YU, L CHUANG, RY TI EXPRESSION OF KAPPA-OPIOID RECEPTORS IN HUMAN AND MONKEY LYMPHOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELLS; MORPHINE; ACTIVATION AB mRNA encoding the kappa opioid receptor gene sequence was identified and isolated from various human lymphocytic cells: CEM x174 (a hybrid of T and B origin) cells, Jurkat-T4 cells, human peripheral blood mononuclear cells (PBMC) and purified CD4+ cells. Analyzing the cDNA sequences of RNA transcripts spanning the putative second extracellular loop, which has reported dynorphin specificity, and the seventh transmembrane domain revealed a 100% and 95% homology in amino acid sequence to corresponding kappa opioid receptor sequences in human placenta and rat brain, respectively. Expression of a similar kappa opioid receptor sequence could be detected in normal monkey PBMC but not in monkey PBMC in which the CD4(+)/CD8(+) cell ratio (or CD4(+) cell number) was significantly reduced due to prolonged SIV infection. These findings suggest that human and monkey lymphocytes constitutively express kappa opioid receptor mRNA. (C) 1995 Academic Press, Inc. C1 UNIV CALIF DAVIS,DEPT MED PHARMACOL & TOXICOL,DAVIS,CA 95616. NCI,FREDERICK,MD 21701. MINNEAPOLIS MED RES FDN INC,MINNEAPOLIS,MN 55404. INDIANA UNIV,DEPT MOLEC & MED GENET,INDIANAPOLIS,IN 46202. FU NIDA NIH HHS [DA05901] NR 33 TC 66 Z9 69 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 26 PY 1995 VL 209 IS 3 BP 1003 EP 1010 DI 10.1006/bbrc.1995.1597 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV602 UT WOS:A1995QV60200030 PM 7733951 ER PT J AU HAHN, JA ZOLOPA, AR MOSS, AR TRACHTENBERG, AL AF HAHN, JA ZOLOPA, AR MOSS, AR TRACHTENBERG, AL TI TUBERCULOSIS TRANSMISSION IN METHADONE-MAINTENANCE PROGRAMS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NATL INST HLTH,ROCKVILLE,MD. RP HAHN, JA (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 26 PY 1995 VL 273 IS 16 BP 1260 EP 1260 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QU571 UT WOS:A1995QU57100026 PM 7715037 ER PT J AU SNELLER, MC AF SNELLER, MC TI WEGENERS GRANULOMATOSIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; HUMAN ENDOTHELIAL-CELLS; ANTICYTOPLASMIC AUTOANTIBODIES; TRIMETHOPRIM-SULFAMETHOXAZOLE; NEUTROPHILS; DIAGNOSIS; ANTIGEN; INFECTION; GLOMERULONEPHRITIS; MYELOPEROXIDASE RP SNELLER, MC (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM IIB-13,BETHESDA,MD 20892, USA. NR 42 TC 25 Z9 25 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 APR 26 PY 1995 VL 273 IS 16 BP 1288 EP 1291 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QU571 UT WOS:A1995QU57100033 PM 7715042 ER PT J AU XU, H RIZZO, LV CASPI, RR AF XU, H RIZZO, LV CASPI, RR TI IL-12 INDUCES GROWTH OF THE IL-4-DEPENDENT CT4S LINE AND HAS A SYNERGISTIC EFFECT ON IL-4-INDUCED CT4S PROLIFERATION SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE IL-4; IL-12; CT4S; IL-4 BIOASSAY ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA PRODUCTION; NATURAL-KILLER-CELLS; CD4+ T-CELLS; FACTOR INTERLEUKIN-12; IMMUNODEFICIENCY; INDUCTION; CYTOKINE; CLONING; MICE AB In the course of studies designed to explore the effect of interleukin 12 (IL-12) on the development of experimental autoimmune uveoretinitis (EAU), we observed that supernatants from IL-12-treated cultures of ocular antigen-specific lymphocytes induced proliferation of the interleukin 4 (IL-4)-dependent CT4S line. This result was surprising, as these supernatants were not expected to contain high levels of IL-4. We therefore explored the possibility that IL-12 itself, that remained in the supernatants, could induce proliferation of CT4S cells. In this series of experiments we demonstrate that CT4S cells proliferate to recombinant as well as to naturally produced IL-12, and that IL-4 and IL-12 synergize in supporting proliferation of CT4S cells. The proliferation induced by IL-12, as well as the synergistic effect with IL-4, can be reversed by neutralizing anti-IL-12 antibodies. Proliferation of CT4S can be abrogated completely by a combination of antibodies against IL-4 and IL-12. Our data have important implications for the use of CT4S as a specific bioassay for IL-4, since both IL-4 and IL-12 may be found together in at least some culture supernatants. Furthermore, our results suggest that the CT4S line (or a derivative selected from it) could be used as a bioassay for detection of IL-12 in combination with the specific antibodies. C1 NEI,IMMUNOL LAB,IMMUNOREGULAT SECT,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 NR 17 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 26 PY 1995 VL 181 IS 2 BP 245 EP 251 DI 10.1016/0022-1759(95)00008-X PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA QW509 UT WOS:A1995QW50900011 PM 7745253 ER PT J AU JI, XH VONROSENVINGE, EC JOHNSON, WW TOMAREV, SI PIATIGORSKY, J ARMSTRONG, RN GILLILAND, GL AF JI, XH VONROSENVINGE, EC JOHNSON, WW TOMAREV, SI PIATIGORSKY, J ARMSTRONG, RN GILLILAND, GL TI 3-DIMENSIONAL STRUCTURE, CATALYTIC PROPERTIES, AND EVOLUTION OF A SIGMA-CLASS GLUTATHIONE TRANSFERASE FROM SQUID, A PROGENITOR OF THE LENS S-CRYSTALLINS OF CEPHALOPODS SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; 3-DIMENSIONAL STRUCTURE; MACROMOLECULAR STRUCTURES; REFINEMENT; RESOLUTION; COMPLEX; ENZYMES; RECRUITMENT; MECHANISM; THETA AB The glutathione transferase from squid digestive gland is unique in its very high catalytic activity toward 1-chloro-2,4-dinitrobenzene and in its ancestral relationship to the genes encoding the S-crystallins of the lens of cephalopod eye. The three-dimensional structure of this glutathione transferase in complex with the product 1-(S-glutathionyl)-2,4-dinitrobenzene (GSDNB) has been solved by multiple isomorphous replacement techniques at a resolution of 2.4 Angstrom. Like the cytosolic enzymes from vertebrates, the squid protein is a dimer. The structure is similar in overall topology to the vertebrate enzymes but has a dimer interface that is unique when compared to all of the vertebrate and invertebrate structures thus far reported. The active site of the enzyme is very open, a fact that appears to correlate with the high turnover number (800 s(-1) at pH 6.5) toward 1-chloro-2,4-dinitrobenzene. Both k(cat) and k(cat)/K-m(CDNB) exhibit pH dependencies consistent with a pK(a) for the thiol of enzyme-bound GSH of 6.3. The enzyme is not very efficient at catalyzing the addition of GSH to enones and epoxides. This particular characteristic appears to be due to the lack of an electrophilic residue at position 106, which is often found in other GSH transferases. The F106Y mutant enzyme is much improved in catalyzing these reactions. Comparisons of the primary structure, gene structure, and three-dimensional structure with class alpha, mu, and pi enzymes support placing the squid protein in a separate enzyme class, sigma. The unique dimer interface suggests that the class sigma enzyme diverged from the ancestral precursor prior to the divergence of the precursor gene for the alpha, mu, and pi classes. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,SHADY GROVE,MD. NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM30910] NR 53 TC 204 Z9 207 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 1995 VL 34 IS 16 BP 5317 EP 5328 DI 10.1021/bi00016a003 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV314 UT WOS:A1995QV31400003 PM 7727393 ER PT J AU PATEL, PH JACOBOMOLINA, A DING, JP TANTILLO, C CLARK, AD RAAG, R NANNI, RG HUGHES, SH ARNOLD, E AF PATEL, PH JACOBOMOLINA, A DING, JP TANTILLO, C CLARK, AD RAAG, R NANNI, RG HUGHES, SH ARNOLD, E TI INSIGHTS INTO DNA POLYMERIZATION MECHANISMS FROM STRUCTURE AND FUNCTION-ANALYSIS OF HIV-1 REVERSE-TRANSCRIPTASE SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; POLYMERASE-I KLENOW; STEADY-STATE KINETICS; DOUBLE-STRANDED DNA; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; FIDELITY; RNA; TEMPLATE; FRAGMENT AB When the single-stranded RNA genome of HIV-1 is copied into double-stranded DNA, the viral enzyme reverse transcriptase (RT) catalyzes the addition of approximately 20 000 nucleotides; however, the precise mechanism of nucleotide addition is unknown. In this study, we attempt to integrate the genetic data and biochemical mechanism of DNA polymerization with the structure of HIV-1 RT complexed with a dsDNA template-primer. The first step of polymerization involves the physical association of a polymerase with its nucleic acid substrate. A comparison of the structures of HIV-1 RT in the presence and absence of DNA indicates that the tip of the p66 thumb moves approximately 30 Angstrom upon DNA binding. This conformational change permits numerous interactions between residues of alpha-helices H and I in the thumb subdomain and the DNA. Measurements of DNA binding affinity for nucleic acids with double-stranded DNAs that have an increasing number of bases in the template overhang and molecular modeling suggest that portions of beta 3 and beta 4 within the fingers subdomain bind single-stranded regions of the template. Measurements of nucleotide incorporation efficiency (k(cat)/K-m) show that the binding and incorporation of the next complementary nucleotide are not dependent on the length of the template overhang. Molecular modeling of an incoming nucleotide triphosphate (dTTP), based in part on the position of mercury atoms in a RT/DNA/Hg-UTP/Fab structure, suggests that portions of secondary structural elements alpha C-beta 6, alpha E, beta 11b, and beta 9-beta 10 determine the topology of the dNTP-binding site. These results also suggest that nucleotide incorporation is accompanied by a protein conformational change that positions the dNTP for nucleophilic attack. Nucleophilic attack by the oxygen atom of the 3'-OH group of the primer strand could be metal-mediated, and Asp185 may be directly involved in stabilizing the transition state. The translocation step may be characterized by rotational as well as translational motions of HIV-1 RT relative to the DNA double helix. Some of the energy required for translocation could be provided by dNTP hydrolysis and could be coupled with conformational changes within the nucleic acid. A structural comparison of HIV-1 RT, Klenow fragment, and T7 RNA polymerase identified regions within T7 RNA polymerase which are not present in the other two polymerases that might help this polymerase to remain bound with nucleic acids and contribute to the ability of the T7 RNA polymerase to polymerize processively. C1 RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-4600]; NIAID NIH HHS [AI26790, AI36144] NR 71 TC 164 Z9 165 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 1995 VL 34 IS 16 BP 5351 EP 5363 DI 10.1021/bi00016a006 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV314 UT WOS:A1995QV31400006 PM 7537090 ER PT J AU RAYMENT, I HOLDEN, HM SELLERS, JR FANANAPAZIR, L EPSTEIN, ND AF RAYMENT, I HOLDEN, HM SELLERS, JR FANANAPAZIR, L EPSTEIN, ND TI STRUCTURAL INTERPRETATION OF THE MUTATIONS IN THE BETA-CARDIAC MYOSIN THAT HAVE BEEN IMPLICATED IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEAVY-CHAIN GENE; MISSENSE MUTATION; MUSCLE-CONTRACTION; NUCLEOTIDE BINDING; ENERGY-TRANSFER; ACTIN FILAMENT; SUBFRAGMENT-1; IDENTIFICATION; SEQUENCE; FORCE AB In 10-30% of hypertrophic cardiomyopathy kindreds, the disease is caused by >29 missense mutations in the cardiac beta-myosin heavy chain (MYH7) gene. The amino acid sequence similarity between chicken skeletal muscle and human beta-cardiac myosin and the three-dimensional structure of the chicken skeletal muscle myosin head have provided the opportunity to examine the structural consequences of these naturally occurring mutations in human beta-cardiac myosin. This study demonstrates that the mutations are related to distinct structural and functional domains. Twenty-four are clustered around four specific locations in the myosin head that are (i) associated with the actin binding interface, (ii) around the nucleotide binding site, (iii) adjacent to the region that connects the two reactive cysteine residues, and (iv) in close proximity to the interface of the heavy chain with the essential light chain. The remaining five mutations are in the myosin rod. The locations of these mutations provide insight into the way they impair the functioning of this molecular motor and also into the mechanism of energy transduction. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NHLBI,INHERITED CARDIAC DIS SECT,BETHESDA,MD 20892. RP RAYMENT, I (reprint author), UNIV WISCONSIN,GRAD SCH,INST ENZYME RES,1710 UNIV AVE,MADISON,WI 53705, USA. FU NIAMS NIH HHS [AR35186] NR 52 TC 169 Z9 176 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 1995 VL 92 IS 9 BP 3864 EP 3868 DI 10.1073/pnas.92.9.3864 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000047 PM 7731997 ER PT J AU KOCISKO, DA PRIOLA, SA RAYMOND, GJ CHESEBRO, B LANSBURY, PT CAUGHEY, B AF KOCISKO, DA PRIOLA, SA RAYMOND, GJ CHESEBRO, B LANSBURY, PT CAUGHEY, B TI SPECIES-SPECIFICITY IN THE CELL-FREE CONVERSION OF PRION PROTEIN TO PROTEASE-RESISTANT FORMS - A MODEL FOR THE SCRAPIE SPECIES BARRIER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED-CELLS; MOUSE SCRAPIE; AGENT PROTEIN; PRP 27-30; HAMSTERS; FIBRILS; GENE; MICE; PHOSPHOLIPASE; TRANSMISSION AB Scrapie is a transmissible neurodegenerative disease that appears to result from an accumulation in the brain of an abnormal protease-resistant isoform of prion protein (PrP) called PrPsc. Conversion of the normal, protease-sensitive form of PrP (PrPc) to protease-resistant forms like PrPsc has been demonstrated in a cell-free reaction composed largely-of hamster PrPc and PrPsc, We now report studies of the species specificity of this cell-free reaction using mouse, hamster, and chimeric PrP molecules, Combinations of hamster PrPc with hamster PrPsc and mouse PrPc with mouse PrPsc resulted in the conversion of PrPc to protease-resistant forms, Protease-resistant PrP species were also generated in the nonhomologous reaction of hamster PrPc with mouse PrPsc, but little conversion was observed in the reciprocal reaction, Glycosylation of the PrPc precursors was not required for species specificity in the conversion reaction, The relative conversion efficiencies correlated with the relative transmissibilities of these strains of scrapie between mice and hamsters, Conversion experiments performed with chimeric mouse/hamster PrPc precursors indicated that differences between PrPc and PrPsc at residues 139, 155, and 170 affected the conversion efficiency and the size of the resultant protease-resistant PrP species. We conclude that there is species specificity in the cell-free interactions that lead to the conversion of PrPc to protease-resistant forms, This specificity may be the molecular basis for the barriers to interspecies transmission of scrapie and other transmissible spongiform encephalopathies in vivo. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 37 TC 297 Z9 308 U1 0 U2 11 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 APR 25 PY 1995 VL 92 IS 9 BP 3923 EP 3927 DI 10.1073/pnas.92.9.3923 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000059 PM 7732006 ER PT J AU WANG, MH IWAMA, A SKEEL, A SUDA, T LEONARD, EJ AF WANG, MH IWAMA, A SKEEL, A SUDA, T LEONARD, EJ TI THE MURINE STK GENE-PRODUCT, A TRANSMEMBRANE PROTEIN-TYROSINE KINASE, IS A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECEPTOR BINDING; HEMATOPOIETIC STEM CELL; PHOSPHORYLATION; TRANSFECTION; KRINGLE ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; EXPRESSION; HOMOLOGY; CLONING; FAMILY; MSP AB Macrophage stimulaling protein (MSP) was originally identified as an inducer of murine resident peritoneal macrophage responsiveness to chemoattractants. We recently showed that the product of RON, a protein tyrosine kinase cloned from a human keratinocyte library, is the receptor for MSP, Similarity of murine stk to RON led us to determine if the stk gene product is the murine receptor for MSP. Radiolabeled MSP could bind to NIH 3T3 cells transfected with murine stk cDNA (3T3/stk), Binding was saturable and was inhibited by unlabeled MSP but not by structurally related proteins, including hepatocyte growth factor and plasminogen, Specific binding to STK was demonstrated by cross-linking of I-125-labeled MSP to membrane proteins of 3T3/stk cells, which resulted in a protein complex with a molecular mass of 220 kDa, This radiolabeled complex comprised I-125-MSP and STK, since it could be immunoprecipitated by antibodies to the STK beta chain. Binding of MSP to stk cDNA-transfected cells induced tyrosine phosphorylation of the 150-kDa STK beta chain within 1 min and caused increased motile activity. These results establish the murine stk gene product as a specific transmembrane protein tyrosine kinase receptor for MSP, Inasmuch as the stk cDNA was cloned from a hematopoietic stem cell, our data suggest that in addition to macrophages and keratinocytes, a cell in the hematopoietic lineage may also be a target for MSP. C1 KUMAMOTO UNIV,SCH MED,INST MOLEC EMBRYOL & GENET,DEPT CELL DIFFERENTIAT,KUMAMOTO 860,JAPAN. RP WANG, MH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702, USA. RI Suda, Toshio/H-6761-2013 OI Suda, Toshio/0000-0001-7540-1771 NR 23 TC 69 Z9 69 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 APR 25 PY 1995 VL 92 IS 9 BP 3933 EP 3937 DI 10.1073/pnas.92.9.3933 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000061 PM 7732008 ER PT J AU MORASSO, MI MAHON, KA SARGENT, TD AF MORASSO, MI MAHON, KA SARGENT, TD TI A XENOPUS DISTAL-LESS GENE IN TRANSGENIC MICE - CONSERVED REGULATION IN DISTAL LIMB EPIDERMIS AND OTHER SITES OF EPITHELIAL-MESENCHYMAL INTERACTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HOMEODOMAIN; TOOTH PRIMORDIUM; INNER EAR; HAIR FOLLICLE; GENITAL TUBERCLE ID HOMEOBOX GENE; DEVELOPING FOREBRAIN; MOUSE EMBRYOS; RESTRICTED EXPRESSION; HOMEODOMAIN PROTEIN; INNER-EAR; DROSOPHILA; PATTERNS; ELEMENT AB In this paper, we show the conserved regulation of the homeodomain gene Distal-less-3 (Dlx-3) by analyzing the expression of a promoter from the Xenopus ortholog, Xdll-2, in transgenic mice. A 470-bp frog regulatory sequence confers appropriate expression on a lacZ reporter gene in the ectodermal component of structures derived from epithelial-mesenchymal interactions. Remarkably, this includes structures absent in Xenopus, such as the hair follicle and mammary gland, suggesting that conserved regulatory elements can be used to control the formation of structures peculiar to individual species. In addition, expression of Dlx-3 in developing limbs is highest at the most distal portion. This pattern is duplicated by the Xenopus promoter, indicating that this DNA may include sequences responsive to conserved proximodistal patterning signals in the vertebrate limb. C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 36 TC 69 Z9 70 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 APR 25 PY 1995 VL 92 IS 9 BP 3968 EP 3972 DI 10.1073/pnas.92.9.3968 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000068 PM 7732014 ER PT J AU ROTHMAN, N HAAS, R HAYES, RB LI, GL WIEMELS, J CAMPLEMAN, S QUINTANA, PJE XI, LJ DOSEMECI, M TITENKOHOLLAND, N MEYER, KB LU, W ZHANG, LP BECHTOLD, W WANG, YZ KOLACHANA, P YIN, SN BLOT, W SMITH, MT AF ROTHMAN, N HAAS, R HAYES, RB LI, GL WIEMELS, J CAMPLEMAN, S QUINTANA, PJE XI, LJ DOSEMECI, M TITENKOHOLLAND, N MEYER, KB LU, W ZHANG, LP BECHTOLD, W WANG, YZ KOLACHANA, P YIN, SN BLOT, W SMITH, MT TI BENZENE INDUCES GENE-DUPLICATING BUT NOT GENE-INACTIVATING MUTATIONS AT THE GLYCOPHORIN-A LOCUS IN EXPOSED HUMANS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SOMATIC CELL MUTATIONS; BIOMARKER ID SOMATIC MUTATIONS; HUMAN-LYMPHOCYTES; A LOCUS; ERYTHROCYTES; WORKERS; CHEMOTHERAPY; METABOLITES; FREQUENCY; TOXICITY; INVOLVE AB Occupational exposure to benzene is known to cause leukemia, but the mechanism remains unclear. Unlike most other carcinogens, benzene and its metabolites are weakly or nonmutagenic in most simple gene mutation assays. Benzene and its metabolites do, however, produce chromosomal damage in a variety of systems, Here, we have used the glycophorin A (GPA) gene loss mutation assay to evaluate the nature of DNA damage produced by benzene in 24 workers heavily exposed to benzene and 23 matched control individuals in Shanghai, China, The GPA assay identifies stem cell or precursor erythroid cell mutations expressed in peripheral erythrocytes of MN-heterozygous subjects, distinguishing the NN and NO mutant variants. A significant increase in the NN GPA variant cell frequency (V-f) was found in benzene-exposed workers as compared with unexposed control individuals (mean +/- SEM, 13.9 +/- 1.7 per million tells vs. 7.4 +/- 1.1 per million cells in control individuals; P = 0.0002). In contrast, no significant difference existed between the two groups for the NO V-f (9.1 +/- 0.9 vs. 8.8 +/- 1.8 per million cells; P = 0.21). Further, lifetime cumulative occupational exposure to benzene was associated with the NN V-f (P = 0.005) but not with the NO V-f (P = 0.31), suggesting that NN mutations occur in longer-lived bone marrow stem cells. NN variants result from loss of the GPA M allele and duplication of the N allele, presumably through recombination mechanisms, whereas NO variants arise from gene inactivation, presumably due to point mutations and deletions, Thus, these results suggest that benzene produces gene-duplicating mutations but does not produce gene-inactivating mutations at the GPA locus in bone marrow cells of humans exposed to high benzene levels. This finding is consistent with data on the genetic toxicology of benzene and its metabolites and adds further weight to the hypothesis that chromosome damage and mitotic recombination are important in benzene-induced leukemia. C1 CALIF DEPT TOX SUBST CONTROL,HAZARDOUS MAT LAB,BERKELEY,CA 94704. CHINESE ACAD PREVENT MED,BEIJING,PEOPLES R CHINA. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. UNIV BRITISH COLUMBIA,OCCUPAT HYG PROGRAM,VANCOUVER,BC,CANADA. SHANGHAI HYG & ANTI EPIDEM CTR,SHANGHAI,PEOPLES R CHINA. LOVELACE INHALAT TOXICOL RES INST,DEPT ENERGY,ALBUQUERQUE,NM 87185. RP ROTHMAN, N (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N 418,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [P30ES01896, P42ES04705] NR 39 TC 63 Z9 67 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 APR 25 PY 1995 VL 92 IS 9 BP 4069 EP 4073 DI 10.1073/pnas.92.9.4069 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000089 PM 7732033 ER PT J AU LAPPALAINEN, J DEAN, M CHARBONNEAU, L VIRKKUNEN, M LINNOILA, M GOLDMAN, D AF LAPPALAINEN, J DEAN, M CHARBONNEAU, L VIRKKUNEN, M LINNOILA, M GOLDMAN, D TI MAPPING OF THE SEROTONIN 5-HT1D-BETA AUTORECEPTOR GENE ON CHROMOSOME-6 AND DIRECT ANALYSIS FOR SEQUENCE VARIANTS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SEROTONIN; SSCP; ALCOHOLISM; CHROMOSOME 6 ID BINDING-SITES; RECEPTOR; ALCOHOLISM; SUBTYPE; MUTATIONS; 5-HT1B AB Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders, Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions, 5-HT1D beta is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release, Using an SSCP technique we screened for 5-HT1D beta, coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA, A common polymorphism was identified in the 5-HT1D beta gene with allele frequencies of 0.72 and 0.28, The SSCP variant was caused by a silent Gr to C substitution at nucleotide 861 of the coding region, This polymorphism could also be detected as a HincII RFLP of amplified DNA, DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6, Multipoint analysis placed the 5-HT1D beta receptor gene between markers D6S286 and D6S275, A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development, This region also contains the gene for North Carolina-type macular dystrophy. (C) 1995 Wiley-Liss, Inc. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,NEUROGENET LAB,ROCKVILLE,MD 20852. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROCKVILLE,MD 20852. NCI,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. HELSINKI UNIV,DEPT PSYCHIAT,HELSINKI,FINLAND. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 34 TC 74 Z9 76 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 24 PY 1995 VL 60 IS 2 BP 157 EP 161 DI 10.1002/ajmg.1320600214 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QT745 UT WOS:A1995QT74500013 PM 7485252 ER PT J AU OZAKI, N LAPPALAINEN, J DEAN, M VIRKKUNEN, M LINNOILA, M GOLDMAN, D AF OZAKI, N LAPPALAINEN, J DEAN, M VIRKKUNEN, M LINNOILA, M GOLDMAN, D TI MAPPING OF THE SEROTONIN 5-HT1D-ALPHA AUTORECEPTOR GENE (HTR1D) ON CHROMOSOME-1 USING A SILENT POLYMORPHISM IN THE CODING REGION SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE BRAIN 5-HT FUNCTION; PSYCHIATRIC DISORDERS; OBSESSIVE-COMPULSIVE DISORDER ID POINT MUTATIONS; RECEPTOR; ALCOHOLISM; DNA C1 NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD 20852. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. UNIV HELSINKI,DEPT PSYCHIAT,SF-00180 HELSINKI,FINLAND. RP OZAKI, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Dean, Michael/G-8172-2012; Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 14 TC 22 Z9 22 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 24 PY 1995 VL 60 IS 2 BP 162 EP 164 DI 10.1002/ajmg.1320600215 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA QT745 UT WOS:A1995QT74500014 PM 7485253 ER PT J AU MANOLIO, TA CUTLER, JA FURBERG, CD PSATY, BM WHELTON, PK APPLEGATE, WB AF MANOLIO, TA CUTLER, JA FURBERG, CD PSATY, BM WHELTON, PK APPLEGATE, WB TI TRENDS IN PHARMACOLOGICAL MANAGEMENT OF HYPERTENSION IN THE UNITED-STATES SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; ANTIHYPERTENSIVE THERAPY; PLASMA-LIPIDS; MYOCARDIAL-INFARCTION; HEART-DISEASE; TRIAL; MORBIDITY; MORTALITY; DIURETICS; LIPOPROTEINS AB Background: Two new classes of antihypertensive agents were introduced in the 1980s, but their effectiveness in preventing heart disease and stroke has not been demonstrated. Lack of evidence of their efficacy might reasonably be expected to discourage their widespread use in management of hypertension. Methods: Use of various classes of antihypertensive agents was estimated from published drug use information in an effort to estimate trends in antihypertensive drug use and evaluate the impact of these trends on costs of antihypertensive therapy in the United States. Results: Proportionate use of the five major antihypertensive drug classes shifted markedly between 1982 and 1993. Diuretics accounted for 56% of all hypertensive drug mentions in 1982 but only 27% in 1993, a relative decline of 52%. Use of beta-blockers and central agents also declined during this period. Proportionate use of calcium antagonists showed the greatest gains, increasing from 0.3% to 27%, while the use of angiotensin-converting enzyme inhibitors increased from 0.8% to 24%. Given the higher costs of the newer agents, and assuming an estimated total cost of antihypertensive medications in 1992 of $7 billion, approximately $3.1 billion would have been saved had 1982 prescribing practices remained in effect in 1992. Conclusion: Use of calcium antagonists and angiotensin-converting enzyme inhibitors in hypertension has increased dramatically in the past 10 years. Without convincing evidence of the advantages of these agents, it is difficult to explain the continued decline in the use of less expensive agents, such as diuretics and beta-blockers, which are the only antihypertensive agents proved to reduce stroke and coronary disease in hypertensive patients. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 301,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 56 TC 165 Z9 168 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD APR 24 PY 1995 VL 155 IS 8 BP 829 EP 837 DI 10.1001/archinte.155.8.829 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA QU594 UT WOS:A1995QU59400007 PM 7717791 ER PT J AU TAKAHASHI, S COOK, M JEHLE, J KENNEDY, C SOKOLOFF, L AF TAKAHASHI, S COOK, M JEHLE, J KENNEDY, C SOKOLOFF, L TI PRESERVATION OF AUTOREGULATORY CEREBRAL VASODILATOR RESPONSES TO HYPOTENSION AFTER INHIBITION OF NITRIC-OXIDE SYNTHESIS SO BRAIN RESEARCH LA English DT Article DE N-G-NITRO-L-ARGININE METHYL ESTER; NITROARGININE; LOCAL CEREBRAL BLOOD FLOW; [C-14] IODOANTIPYRINE; CEREBRAL BLOOD FLOW; BRAIN; AUTOREGULATION ID BLOOD-FLOW; AUTO-REGULATION; GLUCOSE-UTILIZATION; RELAXING FACTOR; RAT; SYNTHASE; ENDOTHELIUM; BRAIN; LOCALIZATION; NUCLEUS AB Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular autoregulatory vasodilator response to hypotension were studied in conscious rats. Cerebral blood flow (CBF) was determined with [C-14]iodoantipyrine in a saline-treated control group and in three groups following inhibition of NO synthase activity by twice daily intraperitoneal injections of 50 mg/kg of N-G-nitro-L-arginine methyl ester (L-NAME) for four days. In the saline-control group (n = 8) and in the L-NAME-treated Group (a)(n = 8) CBF was determined while systemic mean arterial blood pressure (MABP) remained at its resting level (means +/- S.D., 128 +/- 6 and 151 +/- 11 mmHg, respectively). In the other groups CBF was determined after MABP was reduced by blood withdrawal to 118 +/- 9 and 88 +/- 8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated MABP, global CBF was significantly lower in L-NAME-treated Group (a) than in the saline-controls (P < 0.005), indicating cerebral vasoconstriction resulting from inhibition of NO synthesis. Global CBF was not significantly reduced further in the two groups with hypotension. Local CBF in the hypotensive rats showed no significant reductions below values in L-NAME-treated control rats (Group (a)) in 31 of 32 brain structures; the only exception was in the auditory cortex of the severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral vasodilatation to compensate for reduced arterial blood pressure is maintained following inhibition of NO synthesis. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RI Takahashi, Shinichi/L-3454-2013 NR 38 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1995 VL 678 IS 1-2 BP 21 EP 28 DI 10.1016/0006-8993(95)00129-E PG 8 WC Neurosciences SC Neurosciences & Neurology GA QW662 UT WOS:A1995QW66200003 PM 7620890 ER PT J AU COLE, JL LEVENTHAL, L PASTERNAK, GW BOWEN, WD BODNAR, RJ AF COLE, JL LEVENTHAL, L PASTERNAK, GW BOWEN, WD BODNAR, RJ TI REDUCTIONS IN BODY-WEIGHT FOLLOWING CHRONIC CENTRAL OPIOID RECEPTOR SUBTYPE ANTAGONISTS DURING DEVELOPMENT OF DIETARY OBESITY IN RATS SO BRAIN RESEARCH LA English DT Article DE OPIOID; FEEDING; DIETARY OBESITY; MU RECEPTOR; DELTA RECEPTOR; KAPPA RECEPTOR; RAT ID FOOD-INTAKE; NOR-BINALTORPHIMINE; GASTROINTESTINAL TRANSIT; BETA-FUNALTREXAMINE; INGESTIVE BEHAVIOR; OPIATE RECEPTORS; WATER-INTAKE; NALTRINDOLE 5'-ISOTHIOCYANATE; DELTA-ANTINOCICEPTION; DECREASES DEPRIVATION AB Acute administration of long-acting general opioid antagonists reduces body weight and food intake in rats. In contrast, chronic administration of short-acting general opioid antagonists produces transient effects. The present study evaluated whether chronic central administration of selective long-acting antagonists of mu (beta-funaltrexamine, BFNA, 20 mu g), mu(1) (naloxonazine, 50 mu g), delta(1) ([D-Ala(2),Leu(5),Cys(6)]-enkephalin, DALCE, 40 mu g), delta(2) (naltrindole isothiocyanate, NTII, 20 mu g) or kappa (nor-binaltorphamine, NBNI, 20 mu g) opioid receptor subtypes altered weight and intake of rats exposed to a palatable diet of pellets, fat, milk and water, relative to pellet-fed and diet-fed controls. Diet-fed rats receiving chronic vehicle injections significantly increased weight (7-10%) and intake over the 11-day time course. Weight was significantly reduced over the time course in rats administered either BFNA (9%), naloxonazine (12%), DALCE (7%) or NTII (6%). Initial weight reductions failed to persist following chronic NBNI. All antagonists chronically reduced fat intake, but did not systematically alter total intake, pellet intake or milk intake relative to the pattern of weight loss. These data indicate that central mu, mu(1), delta(1), delta(2), and, to a lesser degree, kappa receptors mediate long-term opioid modulation of weight even in animals maintained on diets that ultimately result in dietary obesity. C1 CUNY QUEENS COLL,DEPT PSYCHOL,FLUSHING,NY 11367. CUNY QUEENS COLL,NEUROPSYCHOL DOCTORAL SUBPROGRAM,FLUSHING,NY 11367. CORNELL UNIV,COLL MED,DEPT NEUROL,NEW YORK,NY. CORNELL UNIV,COLL MED,MEM SLOAN KETTERING CANC CTR,GEORGE COTZIAS LAB NEUROONCOL,NEW YORK,NY. CORNELL UNIV,COLL MED,DEPT NEUROSCI & PHARMACOL,NEW YORK,NY. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. FU NIDA NIH HHS [DA07242, DA04194, DA02615] NR 63 TC 36 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1995 VL 678 IS 1-2 BP 168 EP 176 DI 10.1016/0006-8993(95)00181-O PG 9 WC Neurosciences SC Neurosciences & Neurology GA QW662 UT WOS:A1995QW66200019 PM 7620885 ER PT J AU KAPCALA, LP AGUILERA, G AF KAPCALA, LP AGUILERA, G TI MODULATION OF CORTICOTROPIN-RELEASING HORMONE-STIMULATED CYCLIC ADENOSINE-MONOPHOSPHATE PRODUCTION BY BRAIN-CELLS SO BRAIN RESEARCH LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; BRAIN CELL CULTURE; CRH RECEPTOR; EXTRAHYPOTHALAMIC; CAMP; ANTERIOR PITUITARY; MODULATION; CORTICOSTERONE; PROTEIN KINASE C; DEXAMETHASONE; VASOPRESSIN; GLUCOCORTICOID ID ADENYLATE-CYCLASE ACTIVITY; ANTERIOR-PITUITARY CELLS; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; TRANSIENT EXPRESSION; FACTOR RECEPTORS; PRIMARY CULTURE; BETA-ENDORPHIN; VASOPRESSIN; ONTOGENY AB Corticotropin-releasing hormone (CRH) is believed to have a role as an important brain neuroregulator acting through specific receptors coupled to adenylate cyclase in addition to its major role in regulating pituitary adrenocorticotropin synthesis and secretion. To study the potential modulatory effects of various regulators and the central effects of CRH, we studied the effects of phorbol ester myristate acetate (PMA), arginine vasopressin (AVP), corticosterone, dexamethasone, and progesterone on CRH stimulation of cyclic adenosine monophosphate (cAMP) production in extrahypothalamic forebrain cell cultures derived from day 17 gestation fetal rats. These cultures contain CRH receptors with similar characteristics as those in anterior pituitary and brain. CRH (10(-9)-10(-7) M) stimulated cAMP in a dose-dependent fashion and maximal stimulation was clearly seen at 10(-7) M CRH. Incubation of the cells with PMA (10(-7) M), a protein kinase C (PKC) agonist, had no effect on basal cAMP, but potentiated CRH-stimulated cAMP. AVP (10(-8), 10(-7) M) had no effect on basal nor CRH-stimulated cAMP accumulation. Corticosterone (10(-7), 10(-6) M) or dexamethasone (10(-9)-10(-7) M) pre-incubation for 18 h did not diminish basal cAMP levels nor inhibit CRH-induced stimulation of cAMP. However, corticosterone inhibited CRH-induced cAMP production in anterior pituitary cells. Neither did exposure to progesterone (2 x 10(-8) M) modulate basal cAMP, CRH-induced cAMP production nor the potentiation of CRH stimulation by PMA. The data demonstrate that CRH receptors in dissociated fetal extrahypothalamic forebrain cell cultures are coupled to an adenylyl cyclase/cAMP second messenger system similarly as shown in studies with anterior pituitary membranes. The interaction between CRH and other regulators is similar to that in anterior pituitary with regard to synergism by a PKC activator such as PMA, but differs in the lack of glucocorticoid inhibition or AVP potentiation of CRH-stimulated cAMP production. The ability of CRH to stimulate cAMP in fetal brain cells additionally suggests that coupling of the receptor to adenylyl cyclase occurs at an early stage of development. C1 NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BETHESDA,MD 20892. RP KAPCALA, LP (reprint author), UNIV MARYLAND,SCH MED & HOSP,DEPT MED,DIV ENDOCRINOL,BRESSLER RES BLDG,ROOM 8-017,BALTIMORE,MD 21201, USA. FU NINDS NIH HHS [NS-23317] NR 34 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1995 VL 678 IS 1-2 BP 207 EP 212 DI 10.1016/0006-8993(95)00184-R PG 6 WC Neurosciences SC Neurosciences & Neurology GA QW662 UT WOS:A1995QW66200023 PM 7620889 ER PT J AU FREO, U PIETRINI, P PIZZOLATO, G FUREYKURKJIAN, M MERICO, A RUGGERO, S DAM, M BATTISTIN, L AF FREO, U PIETRINI, P PIZZOLATO, G FUREYKURKJIAN, M MERICO, A RUGGERO, S DAM, M BATTISTIN, L TI DOSE-DEPENDENT EFFECTS OF BUSPIRONE ON BEHAVIOR AND CEREBRAL GLUCOSE-METABOLISM IN RATS SO BRAIN RESEARCH LA English DT Article DE BUSPIRONE; RCMRGLC; SEROTONIN 5-HT; DPAT; ANXIOLYTIC ID DISCRIMINATIVE STIMULUS PROPERTIES; RHYTHMICAL SLOW ACTIVITY; CONSCIOUS RAT; 5-HYDROXYTRYPTAMINE(1A) AGONISTS; INDUCED CATALEPSY; ANXIOLYTIC DRUGS; 5-HT1A AGONISTS; BRAIN; HIPPOCAMPUS; RECEPTORS AB In this study we compared the effects df the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)(1A) agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [C-14]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in Iimbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subytpe may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D-2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone. In summary, this study suggests that buspirone produces dual, dose-dependent rCMRglc effects: (i) at a low dose rCMRglc reductions in limbic areas and raphe nuclei, probably due to preferential activation of 5-HT1A receptors, and (ii) at higher doses widespread rCMRglc reductions along with a rCMRglc increase in the lateral habenula resulting from dopamine D-2 receptor blockade. C1 CLIN MALATTIE NERVOSE & MENTALI,I-35100 PADUA,ITALY. CLIN PSICHIAT,I-56100 PISA,ITALY. RP FREO, U (reprint author), NIH,NEUROSCI LAB,BLDG 10 ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 66 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1995 VL 677 IS 2 BP 213 EP 220 DI 10.1016/0006-8993(95)00140-L PG 8 WC Neurosciences SC Neurosciences & Neurology GA QV756 UT WOS:A1995QV75600004 PM 7552245 ER PT J AU HIRATA, H LADENHEIM, B ROTHMAN, RB EPSTEIN, C CADET, JL AF HIRATA, H LADENHEIM, B ROTHMAN, RB EPSTEIN, C CADET, JL TI METHAMPHETAMINE-INDUCED SEROTONIN NEUROTOXICITY IS MEDIATED BY SUPEROXIDE RADICALS SO BRAIN RESEARCH LA English DT Note DE METHAMPHETAMINE; TRANSGENIC MOUSE; FREE RADICAL; SEROTONIN UPTAKE SITE; SUPEROXIDE DISMUTASE ID RAT-BRAIN; 5-HYDROXYTRYPTAMINE; METHYLAMPHETAMINE; DOPAMINE AB Methamphetamine (METH) causes deleterious effects in brain monoaminergic systems. Evidence has accumulated to suggest that these effects may be mediated via the overproduction of the superoxide radicals. We have recently shown that METH-induced dopamine (DA) depletion is attenuated in copper-zinc superoxide dismutase (CuZnSOD) transgenic (Tg) mice. In the present study, we have used receptor autoradiographic studies of [I-125]RTI-55 labeled serotonin (5-HT) uptake sites to evaluate the effect of a two dosing schedule (5 mg/kg or 10 mg/kg X 4) of METH on striatal 5-HT uptake sites in nontransgenic (Non-Tg), heterozygous (Hetero) and homozygous (Home) SOD-Tg mice. The low dose caused no significant changes in striatal 5-HT uptake sites in any of the groups. The high dose caused marked decreases (-74%) in striatal 5-HT uptake sites in Non-Tg mice. In contrast, 5-HT uptake sites showed only a 31% decrease in homozygous SOD-Tg mice whereas heterozygous SOD-Tg mice showed 63% depletion. These results show that increased SOD activity can protect against METH-induced neurotoxicity in striatal serotonergic terminals. These data provide further evidence for a role of oxidative stress in the neurotoxic effects of METH. C1 NIDA,DIV INTRAMURAL RES,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. FU NIA NIH HHS [AG-08938] NR 13 TC 71 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1995 VL 677 IS 2 BP 345 EP 347 DI 10.1016/0006-8993(95)00218-F PG 3 WC Neurosciences SC Neurosciences & Neurology GA QV756 UT WOS:A1995QV75600022 PM 7552263 ER PT J AU KREISS, DS BERGSTROM, DA GONZALEZ, AM HUANG, KX SIBLEY, DR WALTERS, JR AF KREISS, DS BERGSTROM, DA GONZALEZ, AM HUANG, KX SIBLEY, DR WALTERS, JR TI DOPAMINE-RECEPTOR AGONIST POTENCIES FOR INHIBITION OF CELL FIRING CORRELATE WITH DOPAMINE D-3 RECEPTOR-BINDING AFFINITIES SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DOPAMINE D-2 RECEPTOR; DOPAMINE D-3 RECEPTOR; SUBSTANTIA NIGRA PARS COMPACTA; AUTORECEPTOR; SINGLE UNIT RECORDING; 7-OH-DPAT ((+/-)-7-HYDROXY-DIPROPYLAMINOTETRALIN) ID INSITU HYBRIDIZATION HISTOCHEMISTRY; MESSENGER-RNA; RAT-BRAIN; LOCALIZATION; NEURONS; APOMORPHINE; MODULATION; CLONING AB The potencies for in vivo inhibition of substantia nigra pars compacta dopamine single cell firing were determined for apomorphine, BHT 920, N-0923, (+/-)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), pramipexole, quinelorane, quinpirole, RU 24926, U-86170, and U-91356. Significant correlation was obtained between the potencies of these 11 highly efficacious dopamine receptor agonists and the in vitro binding affinities at dopamine D-3 receptors, but not at dopamine D-2L receptors. These results support a functional role for the dopamine D-3 receptor subtype in the autoreceptor-mediated regulation of dopamine cell activity, while a role for dopamine D, receptors awaits further analysis. In addition, the results demonstrate the limitations of using currently available dopamine receptor agonists to delineate relative in vivo roles for the dopamine D-2 and D-3 receptor subtypes. C1 NINCDS,EXPTL THERAPEUT BRANCH,NEUROPHYSIOL PHARMACOL SECT,BETHESDA,MD 20892. NINCDS,EXPTL THERAPEUT BRANCH,MOLEC NEUROPHARMACOL SECT,BETHESDA,MD 20892. NAT INST GEN MED SCI,BETHESDA,MD. NR 16 TC 77 Z9 78 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 24 PY 1995 VL 277 IS 2-3 BP 209 EP 214 DI 10.1016/0014-2999(95)00069-W PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QV760 UT WOS:A1995QV76000012 PM 7493610 ER PT J AU BERZETEIGURSKE, IP WHITE, A POLGAR, W DECOSTA, BR PASTERNAK, GW TOLL, L AF BERZETEIGURSKE, IP WHITE, A POLGAR, W DECOSTA, BR PASTERNAK, GW TOLL, L TI THE IN-VITRO PHARMACOLOGICAL CHARACTERIZATION OF NALOXONE BENZOYLHYDRAZONE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NALOXONE BENZOYLHYDRAZONE; ILEUM, GUINEA PIG; KAPPA-OPIOID RECEPTOR; RECEPTOR BINDING ID GUINEA-PIG BRAIN; KAPPA-OPIOID RECEPTOR; BINDING; LIGAND; OPIATE; ANTAGONIST; MULTIPLICITY; MORPHINE; AGONISTS; INVIVO AB On the basis of its in vivo activity and binding affinity, naloxone benzoylhydrazone has been characterized as a kappa(3)-opioid receptor agonist and a mu-opioid receptor antagonist. This paper continues its pharmacological characterization with the help of isolated tissue preparations. Naloxone benzoylhydrazone was found to have partial agonist activity in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. As an antagonist, naloxone benzoylhydrazone is similar to naloxone, with pA(2) values of 8.8, 7.8, and 7.8 for mu-, delta-, and kappa(1)-opioid receptors, respectively. Its agonist activity in the guinea pig ileum preparation was not influenced by beta-funaltrexamine treatment but was reversed by the selective kappa-opioid receptor antagonist nor-binaltorphimine and by the irreversible kappa(1)-opioid receptor blocker UPHIT (1S,2S)-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-( 1-pyrrolidinyl)-cyclohexyl] benzeneacetamide. The presence of kappa(3)-opioid receptors could not be demonstrated by [H-3]naloxone benzoylhydrazone binding in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. From these studies it is concluded that the partial agonist activity of naloxone benzoylhydrazone in this bioassay is probably due to the activation of the kappa(1)-opioid receptors. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL & PHARMACOL,NEW YORK,NY 10021. RP BERZETEIGURSKE, IP (reprint author), SRI INT,DEPT NEUROSCI,BLDG LA,ROOM 105,333 RAVENSWOOD AVE,MENLO PK,CA 94025, USA. FU NIDA NIH HHS [DA06241, DA06682]; PHS HHS [271-89-8159] NR 23 TC 20 Z9 20 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 APR 24 PY 1995 VL 277 IS 2-3 BP 257 EP 263 DI 10.1016/0014-2999(95)00088-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QV760 UT WOS:A1995QV76000019 PM 7493617 ER PT J AU ARORA, KK SAKAI, A CATT, KJ AF ARORA, KK SAKAI, A CATT, KJ TI STRUCTURE-FUNCTION-RELATIONSHIPS IN GONADOTROPIN-RELEASING-HORMONE RECEPTOR (GNRH-R) - MUTATIONS IN THE 2ND INTRACELLULAR (2I) LOOP AFFECT SIGNAL-TRANSDUCTION AND RECEPTOR INTERNALIZATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1450 EP A1450 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401212 ER PT J AU BAE, YS HWANG, SC RHEE, SG AF BAE, YS HWANG, SC RHEE, SG TI PURIFICATION OF BOVINE LUNG PROTEINS THAT ACTIVATE PLC-GAMMA-1 IN THE PRESENCE OF ARACHIDONIC-ACID SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL SIGNALING LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400741 ER PT J AU BECERRA, SP AF BECERRA, SP TI PEDF BEHAVES AS A NONINHIBITORY SERPIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1439 EP A1439 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401148 ER PT J AU BERLETT, BS YIM, MB CHOCK, PB STADTMAN, ER AF BERLETT, BS YIM, MB CHOCK, PB STADTMAN, ER TI PEROXYNITRITE-PROVOKED NITRATION OF TYROSINE RESIDUES IN GLUTAMINE-SYNTHETASE CAUSES CHANGES IN REGULATORY PROPERTIES SIMILAR TO THOSE OBTAINED BY ATP-DEPENDENT ADENYLYLATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1479 EP A1479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401376 ER PT J AU BOGUSKI, MS AF BOGUSKI, MS TI HOW TO MAKE DISCOVERIES IN MOLECULAR SEQUENCE DATABASES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1259 EP A1259 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400113 ER PT J AU BROYLES, RH BLAIR, FC STEWART, DR KURIEN, BT KYKER, KD HALASZ, H BERG, PE SCHECHTER, AN AF BROYLES, RH BLAIR, FC STEWART, DR KURIEN, BT KYKER, KD HALASZ, H BERG, PE SCHECHTER, AN TI A FERRITIN-LIKE PROTEIN BINDS A HIGHLY CONSERVED CAGTGC MOTIF IN THE HUMAN ADULT BETA-GLOBIN GENE PROMOTER AND CAN MEDIATE DNA LOOPING IN-VITRO SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73190. NATL INST HLTH,BETHESDA,MD 20892. RI Kurien, Biji/C-2392-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1328 EP A1328 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400509 ER PT J AU BRYANT, SD LAZARUS, LH GUERRINI, R SALVADORI, S AF BRYANT, SD LAZARUS, LH GUERRINI, R SALVADORI, S TI MONTE-CARLO ANALYSIS REVEALS A NEW STRUCTURAL MOTIF FOR ULTRASELECTIVE DELTA-OPIOIDMIMETIC DIPEPTIDE ANTAGONISTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1255 EP A1255 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400090 ER PT J AU BUCZKO, E KOH, Y MIYAGAWA, Y DUFAU, ML AF BUCZKO, E KOH, Y MIYAGAWA, Y DUFAU, ML TI HOMOLOGY MODEL OF RAT CYP17 CONSERVED DOMAIN BASED ON THE 3-ALPHA/20-BETA STEROID DEHYDROGENASE (STREPTOMYCES HYDROGENANS) C19 STEROID-BINDING CAVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,ERRB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1265 EP A1265 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400141 ER PT J AU CHAE, HZ KIM, HJ KIM, K RHEE, SG AF CHAE, HZ KIM, HJ KIM, K RHEE, SG TI THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE AND PEROXIREDOXIN FAMILY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL SIGNALING LAB,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1478 EP A1478 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401375 ER PT J AU CHAUTHAIWALE, J TAYLOR, S AMBUDKAR, I AF CHAUTHAIWALE, J TAYLOR, S AMBUDKAR, I TI KINETICS OF CA2+ POOL DEPLETION-ACTIVATED CA2+ ENTRY IN RAT PAROTID ACINAR-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,CIPCB,SECRETORY PHYSIOL SECT,BETHESDA,MD 20892. BAYLOR DENT SCH,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1382 EP A1382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400823 ER PT J AU CHAUTHAIWALE, V WARWAR, R WISTOW, G ZELENKA, P AF CHAUTHAIWALE, V WARWAR, R WISTOW, G ZELENKA, P TI REGULATION OF DUCK ALPHA-ENOLASE PROMOTER BY C-MYC SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1332 EP A1332 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400534 ER PT J AU CHO, J GHOLAMI, N OWENS, IS AF CHO, J GHOLAMI, N OWENS, IS TI DIVERSITY AND INDEPENDENT REGULATION AT THE NOVEL HUMAN UGT1 LOCUS ENCODING 12 UDP-GLUCURONOSYLTRANSFERASE ISOZYMES THROUGH DUPLICATION OF BOTH EXON-1 AND THE UPSTREAM REGULATORY REGION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20853. NR 0 TC 6 Z9 7 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1268 EP A1268 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400160 ER PT J AU CIOTTI, M OBARAY, R MARTIN, M OWENS, IS AF CIOTTI, M OBARAY, R MARTIN, M OWENS, IS TI IDENTIFICATION OF A 2-BASE MUTATION IN THE BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE GENE AT THE UGT1 GENE-COMPLEX LOCUS IN 2 UNRELATED CRIGLER-NAJJAR TYPE-1 PATIENTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90024. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1267 EP A1267 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400154 ER PT J AU COHN, JA FRIGUET, B TSAI, L SZWEDA, LI AF COHN, JA FRIGUET, B TSAI, L SZWEDA, LI TI FORMATION OF 4-HYDROXY-2-NONENAL CROSS-LINKED PROTEIN IN MITOCHONDRIA EXPOSED TO OXIDATIVE STRESS SO FASEB JOURNAL LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. INST PASTEUR,UNITE BIOCHIM CELLULAIRE,F-75724 PARIS,FRANCE. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1479 EP A1479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401380 ER PT J AU CRAWFORD, KW AF CRAWFORD, KW TI A NOVEL-APPROACH TO PREPARING AFFINITY CHROMATOGRAPHIC RESINS USING PHOSPHORYLATED LIGANDS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1385 EP A1385 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400842 ER PT J AU DAVIS, DA DORSEY, KB FALES, HM WINGFIELD, PT STAHL, SJ KAUFMAN, J LEVINE, RL AF DAVIS, DA DORSEY, KB FALES, HM WINGFIELD, PT STAHL, SJ KAUFMAN, J LEVINE, RL TI MIXED DISULFIDE FORMATION REVERSIBLY INHIBITS HIV-1 PROTEASE ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1439 EP A1439 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401152 ER PT J AU DING, L SUN, P COLEMAN, WG AF DING, L SUN, P COLEMAN, WG TI CRYSTALLIZATION OF ADP-L-GLYCERO-D-MANNOHEPTOSE-6-EPIMERASE FROM ESCHERICHIA-COLI K12 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1375 EP A1375 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400784 ER PT J AU DRISCOLL, WJ KOMATSU, K STROTT, CA AF DRISCOLL, WJ KOMATSU, K STROTT, CA TI IDENTIFICATION OF ACTIVE-SITE RESIDUES IN ESTROGEN SULFOTRANSFERASE BY MUTATIONAL ANALYSIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,STEROID REGULAT SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1296 EP A1296 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400329 ER PT J AU DUHE, RJ FARRAR, WL AF DUHE, RJ FARRAR, WL TI CHARACTERIZATION OF ACTIVE AND INACTIVE FORMS OF RAT JAK2 PROTEIN-TYROSINE KINASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1408 EP A1408 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400971 ER PT J AU DUNN, BM GUSTCHINA, A RESHETNIKOVA, L BHATT, D ZHANG, L WLODAWER, A AF DUNN, BM GUSTCHINA, A RESHETNIKOVA, L BHATT, D ZHANG, L WLODAWER, A TI STRUCTURE AND ENZYMOLOGY OF FIV AND HIV PRS - RELATION TO THE DEVELOPMENT OF AIDS DRUG-RESISTANCE SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV FLORIDA,DEPT BIOCHEM & MOLEC BIOL,GAINESVILLE,FL 32610. NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1266 EP A1266 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400150 ER PT J AU FISHER, A SHI, Y TANIUCHI, H AF FISHER, A SHI, Y TANIUCHI, H TI ON THE RESIDUES INVOLVED IN THE HYPOTHETICAL CORE DOMAIN-DOMAIN INTERACTION IN THE CYTOCHROME-C FOLDING SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1243 EP A1243 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400028 ER PT J AU GALAZKA, G BIRKEDALHANSEN, H ENGLER, JA AF GALAZKA, G BIRKEDALHANSEN, H ENGLER, JA TI MUTATIONS IN THE HUMAN PROSL-1 PROPEPTIDE - EFFECT ON ORGANOMERCURIAL ACTIVATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT BIOCHEM & MOLEC GENET,BIRMINGHAM,AL 35294. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401143 ER PT J AU GARCIA, MC KIM, HY AF GARCIA, MC KIM, HY TI RELEASE OF DOCOSAHEXAENOIC ACID (22/6N3) BY RAT C6 GLIOMA-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMBB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1309 EP A1309 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400401 ER PT J AU HU, ZZ ZHUANG, L BUZCKO, E DUFAU, ML AF HU, ZZ ZHUANG, L BUZCKO, E DUFAU, ML TI ROLES OF THE 3'-NONCODING REGION IN POSTTRANSCRIPTIONAL PROCESSES OF THE RAT LH RECEPTOR GENE-EXPRESSION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,ERRB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1276 EP A1276 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400209 ER PT J AU IBEANU, GC GHANAYEM, BI LINKO, P GOLDSTEIN, JA AF IBEANU, GC GHANAYEM, BI LINKO, P GOLDSTEIN, JA TI IDENTIFICATION OF STRUCTURAL DETERMINANTS OF S-MEPHENYTOIN 4'-HYDROXYLASE ACTIVITY USING CYP2C9/CYP2C19 CHIMERAS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1489 EP A1489 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401436 ER PT J AU JOE, YA WOLFF, EC PARK, MH AF JOE, YA WOLFF, EC PARK, MH TI ISOLATION AND CHARACTERIZATION OF CDNAS ENCODING HUMAN DEOXYHYPUSINE SYNTHASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1336 EP A1336 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400558 ER PT J AU KANG, KR WOLFF, EC PARK, MH FOLK, JE CHUNG, SI AF KANG, KR WOLFF, EC PARK, MH FOLK, JE CHUNG, SI TI IDENTIFICATION OF YHR068W IN SACCHAROMYCES-CEREVISIAE CHROMOSOME-VIII AS A GENE FOR DEOXYHYPUSINE SYNTHASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1425 EP A1425 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401068 ER PT J AU KASUYA, J GOKO, H KATO, K MANGANIELLO, VC FUJITAYAMAGUCHI, Y AF KASUYA, J GOKO, H KATO, K MANGANIELLO, VC FUJITAYAMAGUCHI, Y TI MULTIPLE TRANSCRIPTS FOR THE HUMAN CARDIAC TYPE CGMP-INHIBITED CYCLIC-AMP PHOSPHODIESTERASE (HCGIP2 TYPE-III PDE) SO FASEB JOURNAL LA English DT Meeting Abstract C1 BECKMAN RES INST,DUARTE,CA. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1263 EP A1263 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400132 ER PT J AU KIM, IY STADTMAN, TC AF KIM, IY STADTMAN, TC TI IMMUNOLOGICAL DETECTION OF SELENOPHOSPHATE SYNTHETASE IN BACTERIA AND RAT-TISSUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401133 ER PT J AU KIM, JM KIM, IH FIBACH, E RODGERS, GP CHOI, YC AF KIM, JM KIM, IH FIBACH, E RODGERS, GP CHOI, YC TI CHROMOSOMAL STRUCTURE OF HEMOGLOBINOPATHIES IN SOUTH-KOREA SO FASEB JOURNAL LA English DT Meeting Abstract C1 DONG A UNIV,LIFE SCI RES INST,PUSAN 602103,SOUTH KOREA. NIDDK,BIOL CHEM LAB,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1270 EP A1270 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400173 ER PT J AU KIM, SY CHUNG, SI STEINERT, PM AF KIM, SY CHUNG, SI STEINERT, PM TI THE PROCESSING OF THE TRANSGLUTAMINASE-I IN KERATINOCYTE INCREASE TOTAL SOLUBLE TRANSGLUTAMINASE ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD. NIDR,LDCO,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1485 EP A1485 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401413 ER PT J AU KLAUSNER, RD AF KLAUSNER, RD TI THE GENETICS AND BIOCHEMISTRY OF EUKARYOTIC IRON-METABOLISM SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1391 EP A1391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400871 ER PT J AU KONG, SK YIM, MB STADTMAN, ER CHOCK, PB AF KONG, SK YIM, MB STADTMAN, ER CHOCK, PB TI PEROXYNITRITE DISABLES THE TYROSINE PHOSPHORYLATION REGULATORY MECHANISM BY NITRATING THE TYROSINE RESIDUE - TYROSINE KINASE FAILS TO PHOSPHORYLATE NITRATED TYROSINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 7 Z9 7 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1303 EP A1303 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400366 ER PT J AU KROOG, GS SAINZ, E WORLAND, PJ AKESON, MA JENSEN, RT BATTEY, JF AF KROOG, GS SAINZ, E WORLAND, PJ AKESON, MA JENSEN, RT BATTEY, JF TI RAPID, AGONIST-INDUCED PHOSPHORYLATION OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR BY A KINASE DISTINCT FROM PROTEIN-KINASE-C SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DCT,DTP,BIOL CHEM LAB,BETHESDA,MD. NIDDK,DIGEST DIS BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1452 EP A1452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401224 ER PT J AU KROUTIL, LC AF KROUTIL, LC TI CONTRIBUTION OF EXONUCLEOLYTIC PROOFREADING TO FRAMESHIFT FIDELITY AT REPETITIVE TRACTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1324 EP A1324 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400486 ER PT J AU KUNDU, GC MUKHERJEE, AB AF KUNDU, GC MUKHERJEE, AB TI SUPPRESSION OF GROUP-I PHOSPHOLIPASE A(2)-INDUCED CELLULAR INVASION OF NIH 3T3 CELLS BY RECOMBINANT HUMAN UTEROGLOBIN VIA SPECIFIC, HIGH-AFFINITY BINDING-SITE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HGB,DEV GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1502 EP A1502 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401511 ER PT J AU KUNDU, GC MUKHERJEE, AB AF KUNDU, GC MUKHERJEE, AB TI SUPPRESSION OF GROUP-I PHOSPHOLIPASE A(2)-INDUCED CELLULAR INVASION OF NIH 3T3 CELLS BY RECOMBINANT HUMAN UTEROGLOBIN VIA SPECIFIC, HIGH-AFFINITY BINDING-SITE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HGB,DEV GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1500 EP A1500 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401502 ER PT J AU KYOSTIO, SRM WONDERLING, RS OWENS, RA AF KYOSTIO, SRM WONDERLING, RS OWENS, RA TI EVIDENCE FOR MULTIPLE MECHANISMS OF GENE REPRESSION OF THE ADENOASSOCIATED VIRUS (AAV) P-5 PROMOTER BY AAV REP SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1273 EP A1273 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400194 ER PT J AU LEE, GR KIM, SN HONG, SH PARK, SD CHOCHUNG, YS AF LEE, GR KIM, SN HONG, SH PARK, SD CHOCHUNG, YS TI AUTOPHOSPHORYLATION MUTANT OF TYPE-I REGULATORY SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE (PKA) INHIBITS CELL-GROWTH SO FASEB JOURNAL LA English DT Meeting Abstract C1 SEOUL NATL UNIV,SEOUL,SOUTH KOREA. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1303 EP A1303 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400369 ER PT J AU LEE, SB NOH, Y RHEE, SG AF LEE, SB NOH, Y RHEE, SG TI CHANGES OF NUCLEAR PHOSPHOLIPASE-C ISOZYMES DURING LIVER-REGENERATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL SIGNALING LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400744 ER PT J AU LEHEL, C PETROVICS, G OLAN, Z JAKAB, G SZALLASI, Z BLUMBERG, PM ANDERSON, WB AF LEHEL, C PETROVICS, G OLAN, Z JAKAB, G SZALLASI, Z BLUMBERG, PM ANDERSON, WB TI PROTEIN-KINASE-C-EPSILON IS LOCALIZED TO THE GOLGI - IDENTIFICATION OF PKC-EPSILON SUBCELLULAR-LOCALIZATION DOMAINS AND PROTEOLYTIC DEGRADATION SITES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1408 EP A1408 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400970 ER PT J AU LEWISCH, SA LEVINE, RL AF LEWISCH, SA LEVINE, RL TI IDENTIFICATION OF 2-OXO-HISTIDINE AS A PRODUCT OF PROTEIN OXIDATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1319 EP A1319 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400463 ER PT J AU LI, H PANAYIOTAKIS, A WANG, CD THOMPSON, D SETH, A AF LI, H PANAYIOTAKIS, A WANG, CD THOMPSON, D SETH, A TI IDENTIFICATION AND CHARACTERIZATION OF GENES DIFFERENTIALLY EXPRESSED IN NORMAL AND BREAST-CARCINOMA TISSUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1282 EP A1282 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400242 ER PT J AU LIU, SY STADTMAN, TC AF LIU, SY STADTMAN, TC TI ISOLATION AND CHARACTERIZATION OF SELENOPHOSPHATE SYNTHETASE MODIFIED BY REACTION WITH ATP SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401131 ER PT J AU LIYANAGE, MS LEE, CH BRISTOL, JA PARK, DJ RHEE, SG AF LIYANAGE, MS LEE, CH BRISTOL, JA PARK, DJ RHEE, SG TI ANALYSIS OF THE PLECKSTRIN HOMOLOGY DOMAIN IN PLC-BETA-3 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1412 EP A1412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400995 ER PT J AU MAHMOODIAN, F PETERKOFSKY, B AF MAHMOODIAN, F PETERKOFSKY, B TI REGULATION OF BONE ALKALINE-PHOSPHATASE DURING VITAMIN-C-DEFICIENCY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1424 EP A1424 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401064 ER PT J AU MINETTI, CA REMETA, DP LIANG, SM TAI, JY AF MINETTI, CA REMETA, DP LIANG, SM TAI, JY TI STRUCTURAL STABILITY OF RECOMBINANT PORINS FROM NEISSERIA-MENINGITIDIS AND HAEMOPHILUS-INFLUENZA SO FASEB JOURNAL LA English DT Meeting Abstract C1 N AMER VACCINE INC,BELTSVILLE,MD 20705. NHLBI,BETHESDA,MD 20892. RI Minetti, Conceicao/B-5077-2009 OI Minetti, Conceicao/0000-0002-9682-2898 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1465 EP A1465 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401296 ER PT J AU MINNICK, DT BELL, JB BEBENEK, K ECKERT, KA JOYCE, CM AF MINNICK, DT BELL, JB BEBENEK, K ECKERT, KA JOYCE, CM TI FIDELITY OF MUTANT DERIVATIVES OF KLENOW FRAGMENT DNA-POLYMERASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. YALE UNIV,DEPT MOLEC BIOPHYS & BIOCHEM,NEW HAVEN,CT 06520. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401163 ER PT J AU MOORE, RC OKA, T AF MOORE, RC OKA, T TI LIGAND-INDUCED ACTIVATION OF PROLACTIN RECEPTOR AND A CHIMERIC GROWTH-HORMONE RECEPTOR PROLACTIN RECEPTOR SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1414 EP A1414 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401006 ER PT J AU MURATA, T TAIRA, M MANGANIELLO, VC AF MURATA, T TAIRA, M MANGANIELLO, VC TI STRUCTURE-FUNCTION ANALYSIS OF RECOMBINANT TYPE-III CGMP-INHIBITED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE (PDE3) - USE OF N-TERMINAL REGION DELETION RECOMBINANTS TO STUDY PDE3 MEMBRANE-ASSOCIATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1262 EP A1262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400128 ER PT J AU NETTO, LES CHAE, HZ RHEE, SG STADTMAN, ER AF NETTO, LES CHAE, HZ RHEE, SG STADTMAN, ER TI TSA HAS 2 DIFFERENT ANTIOXIDANT MECHANISMS DEPENDING ON THE INITIAL CONCENTRATION OF HYDROGEN-PEROXIDE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401130 ER PT J AU NIELSEN, DA SCHUEBEL, KE RASKIN, JS JENKINS, GL GOLDMAN, D AF NIELSEN, DA SCHUEBEL, KE RASKIN, JS JENKINS, GL GOLDMAN, D TI TRYPTOPHAN-HYDROXYLASE GENE-EXPRESSION STUDIES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,LN,MOLEC GENET SECT,ROCKVILLE,MD 20852. RI Nielsen, David/B-4655-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1462 EP A1462 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401277 ER PT J AU OIN, KF KHANGULOV, S LIU, C HUANG, CY AF OIN, KF KHANGULOV, S LIU, C HUANG, CY TI ROLE OF FE ION IN CALCINEURIN STUDIED BY ERP AND ACTIVITY MEASUREMENTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1347 EP A1347 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400622 ER PT J AU OSAWA, Y NAKATSUKA, K NAKATSUKA, M AF OSAWA, Y NAKATSUKA, K NAKATSUKA, M TI INACTIVATION OF PENILE NITRIC-OXIDE SYNTHASE BY GUANABENZ, AN ANTIHYPERTENSIVE AGENT - POTENTIAL IMPLICATIONS IN DRUG-INDUCED IMPOTENCE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,MOLEC IMMUNOL LAB,MOLEC & CELLULAR TOXICOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1495 EP A1495 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401471 ER PT J AU PARALKAR, V WISTOW, G AF PARALKAR, V WISTOW, G TI MIF - AN ESSENTIAL INTERMEDIATE FOR GROWTH-FACTOR INDUCED MITOGENESIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,MOLEC & DEV BIOL LAB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1332 EP A1332 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400532 ER PT J AU PERFETTI, R MONTROSERAFIZADEH, C BERNIER, M AF PERFETTI, R MONTROSERAFIZADEH, C BERNIER, M TI CELLULAR EXPRESSION OF MUTANT INSULIN-RECEPTORS INTERFERES WITH THE INDUCTION OF ERCC-1 EXPRESSION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,DIABET UNIT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1401 EP A1401 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400931 ER PT J AU PETROVICS, G LEHEL, C OLAH, Z ANDERSON, WB AF PETROVICS, G LEHEL, C OLAH, Z ANDERSON, WB TI PROTEIN-KINASE C-MEDIATED GROWTH-INHIBITION OF NIH-3T3 CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1408 EP A1408 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400973 ER PT J AU PTITSYN, OB UVERSKY, VN AF PTITSYN, OB UVERSKY, VN TI PRE-MOLTEN GLOBULE - A NEW EQUILIBRIUM STATE OF PROTEIN MOLECULES SO FASEB JOURNAL LA English DT Meeting Abstract C1 INST PROT RES,PUSHCHINO 142292,RUSSIA. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1469 EP A1469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401321 ER PT J AU RAHN, T STENSONHOLST, L BELFRAGE, P MANGANIELLO, V DEGERMAN, E AF RAHN, T STENSONHOLST, L BELFRAGE, P MANGANIELLO, V DEGERMAN, E TI PARTIAL-PURIFICATION AND CHARACTERIZATION OF AN INSULIN-STIMULATED CGI-PDE KINASE IN RAT ADIPOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 LUND UNIV,DEPT MOLEC & CELL BIOL,MOLEC SIGNALLING SECT,LUND,SWEDEN. NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1262 EP A1262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400127 ER PT J AU RUBALTELLI, D CIOTTI, M RUBALTELLI, FF OWENS, IS AF RUBALTELLI, D CIOTTI, M RUBALTELLI, FF OWENS, IS TI 2 DIFFERENT MISSENSE MUTATIONS AT THE UGT1 GENE-COMPLEX LOCUS THAT GENERATE PH-SENSITIVE ACTIVITY OF THE MAJOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE IN CRIGLER-NAJJAR TYPE-II PATIENTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV PADUA,DIPARTIMENTO PEDIAT,I-35128 PADUA,ITALY. NR 0 TC 3 Z9 3 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1267 EP A1267 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400157 ER PT J AU SAKAI, T AMBUDKAR, IS AF SAKAI, T AMBUDKAR, IS TI INVOLVEMENT OF PROTEIN PHOSPHATASE IN THE STIMULATION OF INTERNAL CA2+ RELEASE-ACTIVATED CA2+ ENTRY MECHANISM IN RAT PAROTID-GLAND ACINAR-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1382 EP A1382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400822 ER PT J AU SELKIRK, JK HE, CY MERRICK, BA AF SELKIRK, JK HE, CY MERRICK, BA TI COMPARATIVE EXPRESSION OF P53 TUMOR-SUPPRESSOR PROTEIN ISOFORMS IN HUMAN AND MURINE CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1272 EP A1272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400185 ER PT J AU SHEN, FS YU, G FELSTED, RL AF SHEN, FS YU, G FELSTED, RL TI INTERACTION BETWEEN HIV-1 P55 AND F-ACTIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DCT,LBC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1279 EP A1279 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400223 ER PT J AU SHEN, L HUANG, FL AF SHEN, L HUANG, FL TI CELL CYCLE-DEPENDENT PHOSPHORYLATION OF HASBP28 BY CASEIN KINASE-II SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1301 EP A1301 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400354 ER PT J AU SILVERMAN, JA BROWN, PC HILL, BA AF SILVERMAN, JA BROWN, PC HILL, BA TI DNA-DAMAGING AGENTS REGULATE THE EXPRESSION OF THE RAT MDR1B GENE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1316 EP A1316 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400445 ER PT J AU SKOWYRA, D WICKNER, S AF SKOWYRA, D WICKNER, S TI GRPE FACILITATES THE UTILIZATION OF MG2+ BY DNAK ATPASE AND LOWERS THE AFFINITY OF DNAK FOR NUCLEOTIDES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1469 EP A1469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401319 ER PT J AU SKOWYRA, D WICKNER, S AF SKOWYRA, D WICKNER, S TI GRPE FACILITATES THE UTILIZATION OF MG2+ BY DNAK ATPASE AND LOWERS THE AFFINITY OF DNAK FOR NUCLEOTIDES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1247 EP A1247 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400049 ER PT J AU SUN, SJ ERICKSON, JW BURT, SK AF SUN, SJ ERICKSON, JW BURT, SK TI PROTEIN BACKBONE CONFORMATION PREFERENCE AND RESCUE BASED BACKBONE ENTROPY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1471 EP A1471 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401330 ER PT J AU SUNHOFFMAN, L AURIGEMMA, R RUSCETTI, S AF SUNHOFFMAN, L AURIGEMMA, R RUSCETTI, S TI REGIONS OF THE GATA-1 PROMOTER REQUIRED FOR TRANSACTION BY THE MOUSE RETROVIRUS ME26 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1281 EP A1281 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400240 ER PT J AU TABOR, CW TABOR, H AF TABOR, CW TABOR, H TI POLYAMINES - BIOSYNTHESIS AND FUNCTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1389 EP A1389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400863 ER PT J AU TSAI, SC ADAMIK, R MOSS, J VAUGHAN, M AF TSAI, SC ADAMIK, R MOSS, J VAUGHAN, M TI PURIFICATION AND CHARACTERIZATION OF A BREFELDIN-A - INSENSITIVE GUANINE NUCLEOTIDE-EXCHANGER PROTEIN (GEP) FOR ARFS-1 AND ARFS-3 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,PCCMB BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1475 EP A1475 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401353 ER PT J AU TSAIMORRIS, CH GENG, Y BUCZKO, E DUFAU, ML AF TSAIMORRIS, CH GENG, Y BUCZKO, E DUFAU, ML TI CHARACTERIZATION OF DIVERSE FUNCTIONAL ELEMENTS IN THE UPSTREAM SP1 DOMAIN OF THE RAT LUTEINIZING-HORMONE RECEPTOR GENE PROMOTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,ERRB,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1327 EP A1327 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400503 ER PT J AU UBAGAI, T LEI, KJ MUDD, HS CHOU, JY AF UBAGAI, T LEI, KJ MUDD, HS CHOU, JY TI MOLECULAR-GENETICS OF HEPATIC METHIONINE ADENOSYL-TRANSFERASE DEFICIENCY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1442 EP A1442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401168 ER PT J AU WOLFF, EC LEE, YB CHUNG, SI PARK, MH FOLK, JE AF WOLFF, EC LEE, YB CHUNG, SI PARK, MH FOLK, JE TI PURIFICATION AND PARTIAL CHARACTERIZATION OF DEOXYHYPUSINE SYNTHASE FROM RAT TESTIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1434 EP A1434 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401123 ER PT J AU WOLFFE, AP BOUVET, P DASSO, M DIMITROV, S HAYES, JJ NIGHTINGALE, K PRUSS, D URA, K AF WOLFFE, AP BOUVET, P DASSO, M DIMITROV, S HAYES, JJ NIGHTINGALE, K PRUSS, D URA, K TI HISTONE H1 AND THE NUCLEOSOME, ROLES IN NUCLEAR-STRUCTURE AND TRANSCRIPTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI dimitrov, stefan/M-7697-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1388 EP A1388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400858 ER PT J AU WU, AJ BAUM, BJ CHEN, ZJ AMBUDKAR, IS AF WU, AJ BAUM, BJ CHEN, ZJ AMBUDKAR, IS TI INTERFERON-GAMMA INDUCES DEPLETION OF INTRACELLULAR CA2+ STORES AND INHIBITS CELL-PROLIFERATION OF A HUMAN SALIVARY-GLAND CELL-LINE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,CIPCB,BETHESDA,MD 20892. NIDR,LOM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1382 EP A1382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400825 ER PT J AU WU, C TSUKIYAMA, T AF WU, C TSUKIYAMA, T TI TRANSCRIPTION FACTOR-MEDIATED NUCLEOSOME DISRUPTION AT A HEAT-SHOCK PROMOTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1388 EP A1388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400855 ER PT J AU XIE, TD TSONG, TY CHEN, YD MARSZALEK, P AF XIE, TD TSONG, TY CHEN, YD MARSZALEK, P TI PROPERTIES OF ELECTROCONFORMATIONAL COUPLING (ECC) - ACTIVATION OF NA,K-ATPASE BY ELECTRIC PULSES OF FLUCTUATING LIFETIME AND FLUCTUATING AMPLITUDE SO FASEB JOURNAL LA English DT Meeting Abstract C1 HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIDDKD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1339 EP A1339 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400573 ER PT J AU ZHAN, XV CROUCH, RJ AF ZHAN, XV CROUCH, RJ TI ANALYSIS OF CHIMERIC E-COLI-AKR MULV RNASE-H PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1249 EP A1249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400057 ER PT J AU ZHAN, XY CROUCH, RJ AF ZHAN, XY CROUCH, RJ TI THE ISOLATED ACTIVE AKR MULV RNASE-H DOMAIN RETAINS ACTIVITY BUT LOSES SPECIFICITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1396 EP A1396 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400901 ER PT J AU ZHUO, SQ KAUFMAN, S AF ZHUO, SQ KAUFMAN, S TI THE SOLE OF RETINOBLASTOMA PROTEIN IN TERMINAL DIFFERENTIATION OF MURINE ERYTHROLEUKEMIA-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1280 EP A1280 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400234 ER PT J AU ZOLKIEWSKA, A MOSS, J AF ZOLKIEWSKA, A MOSS, J TI PROCESSING OF ADP-RIBOSYLATED INTEGRIN ALPHA-7 IN SKELETAL-MUSCLE MYOTUBES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1504 EP A1504 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401521 ER PT J AU ZOLKIEWSKI, M NOSWORTHY, NJ GINSBURG, A AF ZOLKIEWSKI, M NOSWORTHY, NJ GINSBURG, A TI UREA INDUCED DISSOCIATION AND UNFOLDING OF DODECAMERIC GLUTAMINE-SYNTHETASE FROM ESCHERICHIA-COLI - CALORIMETRIC AND SPECTRAL STUDIES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1241 EP A1241 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400013 ER PT J AU GIVOL, I BOYER, PL HUGHES, SH AF GIVOL, I BOYER, PL HUGHES, SH TI ISOLATION AND CHARACTERIZATION OF THE CHICKEN C-SNO GENE SO GENE LA English DT Note DE CLONING; DNA SEQUENCING; TRANSCRIPTIONAL INITIATION; PROMOTER; HOMOLOGY ID SKI ONCOGENE; CDNA CLONES; SEQUENCE; TRANSCRIPTION; JUNCTION; PROTEIN; MUSCLE; EXONS; VIRUS AB We have cloned and analyzed the chicken c-sno (cellular ski novel) gene. The promoter region and all of the intron/exon boundaries have been sequenced. The gene is approx. 12-kb long and contains six exons, the first of which is noncoding. The amino-acid sequences encoded in this first coding exon of c-sno and c-ski are highly related; however, the remainder of these two genes appears to be unrelated. Although there is evidence that the transcripts of mammalian c-sno are alternatively spliced, there is no evidence that chicken c-sno is alternatively spliced. The promoter region has a high GS+C content and contains neither a TATAA nor a CAAT box. Potential binding sites for the transcription factors SP1, AP1 and AP2, are present upstream from the transcription start point. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 22 TC 10 Z9 10 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 APR 24 PY 1995 VL 156 IS 2 BP 271 EP 276 DI 10.1016/0378-1119(95)00066-F PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QW708 UT WOS:A1995QW70800017 PM 7758967 ER PT J AU LIANG, XA KINGSTON, DGI LIN, CM HAMEL, E AF LIANG, XA KINGSTON, DGI LIN, CM HAMEL, E TI SYNTHESIS AND BIOLOGICAL EVALUATION OF PACLITAXEL ANALOGS MODIFIED IN RING-C SO TETRAHEDRON LETTERS LA English DT Article ID MODIFIED TAXOLS; ANTITUMOR AGENTS; OXIDATION; CANCER; DRUG AB Both 7-deoxy-7 alpha-azidopaclitaxel (6) and 7-deoxy-Delta(6,7)-paclitaxel (4) can be prepared from paclitaxel-7-0-triflate (2b). Oxidation of 7-deoxy-Delta(6,7)-paclitaxel with dioxirane yields the epoxide 7, while oxidation with osmium tetroxide yields 6 alpha-hydroxy-7-epipaclitaxel (9), and acylation of this gives the 6 alpha-acyloxy-7-epipaclitaxel derivatives 11a-d. No compound was as effective at promoting tubulin assembly as paclitaxel, but most stabilized polymer as well as or better than paclitaxel. Compounds 4, 6, 7, 9, and 11d differed little from paclitaxel in their cytotoxicity for human Burkitt lymphoma CA46 cells. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. OI Kingston, David/0000-0001-8944-246X NR 23 TC 23 Z9 25 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD APR 24 PY 1995 VL 36 IS 17 BP 2901 EP 2904 DI 10.1016/0040-4039(95)00431-B PG 4 WC Chemistry, Organic SC Chemistry GA QV358 UT WOS:A1995QV35800003 ER PT J AU WALLQVIST, A ASTRAND, PO AF WALLQVIST, A ASTRAND, PO TI LIQUID DENSITIES AND STRUCTURAL-PROPERTIES OF MOLECULAR-MODELS OF WATER SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID EFFECTIVE PAIR POTENTIALS; CENTRAL-FORCE MODEL; DYNAMICS; SIMULATION; TEMPERATURE C1 LUND UNIV,S-22100 LUND,SWEDEN. RP WALLQVIST, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP INC,FREDERICK,MD 21702, USA. RI Astrand, Per-Olof/H-6879-2012 OI Astrand, Per-Olof/0000-0003-3384-7585 NR 42 TC 37 Z9 37 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 22 PY 1995 VL 102 IS 16 BP 6559 EP 6565 DI 10.1063/1.469370 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA QU333 UT WOS:A1995QU33300022 ER PT J AU KWAK, LW TAUB, DD DUFFEY, PL BENSINGER, WI BRYANT, EM REYNOLDS, CW LONGO, DL AF KWAK, LW TAUB, DD DUFFEY, PL BENSINGER, WI BRYANT, EM REYNOLDS, CW LONGO, DL TI TRANSFER OF MYELOMA IDIOTYPE-SPECIFIC IMMUNITY FROM AN ACTIVELY IMMUNIZED MARROW DONOR SO LANCET LA English DT Article ID BONE-MARROW; T-CELLS; TRANSPLANTATION; SURFACE AB The idiotype of myeloma immunoglobulin can be used as a unique tumour-specific antigen. We tested the hypothesis that tumour antigen-specific immunity can be transferred from bone-marrow-transplant donor to recipient. We immunised a healthy sibling donor with myeloma immunoglobulin from the plasma of the recipient, conjugated to an immunogenic carrier protein and emulsified in an adjuvant, before marrow transplantation. Detection of a lymphoproliferative response, a parallel response in the carrier protein, recovery of a recipient CD4+ T-cell line with unique specificity for myeloma idiotype, and demonstration by in-situ hybridisation that the cell line was of donor origin, proved that a myeloma idiotype-specific T-cell response was successfully transferred to the recipient. Donor immunisation with myeloma idiotype may represent a new strategy for enhancing the specific antitumour effect of allogeneic marrow grafts. C1 PROGRAM RESOURCES INC DYNCORP,CLIN IMMUNOL SERV,FREDERICK,MD. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP KWAK, LW (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 15 TC 217 Z9 222 U1 0 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD APR 22 PY 1995 VL 345 IS 8956 BP 1016 EP 1020 DI 10.1016/S0140-6736(95)90757-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA QU573 UT WOS:A1995QU57300009 PM 7723498 ER PT J AU MARCILLA, A RIVEROLEZCANO, OM AGARWAL, A ROBBINS, KC AF MARCILLA, A RIVEROLEZCANO, OM AGARWAL, A ROBBINS, KC TI IDENTIFICATION OF THE MAJOR TYROSINE KINASE SUBSTRATE IN SIGNALING COMPLEXES FORMED AFTER ENGAGEMENT OF FC-GAMMA RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYLATION; PROTEIN; CELLS; P72(SYK); ONCOGENE; CBL AB We have recently identified the protein product of the c-cbl proto oncogene as an SH3 binding protein expressed in macrophages. To investigate the possibility that p120(c-cbl) is involved in signaling pathways initiated by cell surface receptors for IgG (Fc gamma R), lysates of HL60 cells were examined for tyrosine phosphorylation of p120(c-cbl) upon Fc gamma R engagement. Our findings demonstrate that p120(c-cbl) is tyrosine-phosphorylated upon Fc gamma R engagement and that this molecule represents the major tyrosine kinase substrate in this signaling pathway. Protein complexes containing p120(c-cbl), p72(syk), and p56(lyn) were observed either in resting or activated cells. In vitro studies showed that the direct association between p120(c-cbl) and p56(lyn) was mediated by the SH3 domain of p56(lyn). C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI marcilla, antonio/F-9996-2010; Rivero-Lezcano, Octavio/J-9089-2015 OI marcilla, antonio/0000-0003-0004-0531; Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 23 TC 128 Z9 128 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 APR 21 PY 1995 VL 270 IS 16 BP 9115 EP 9120 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900013 PM 7721825 ER PT J AU BENBARUCH, A BENGALI, KM BIRAGYN, A JOHNSTON, JJ WANG, JM KIM, J CHUNTHARAPAI, A MICHIEL, DF OPPENHEIM, JJ KELVIN, DJ AF BENBARUCH, A BENGALI, KM BIRAGYN, A JOHNSTON, JJ WANG, JM KIM, J CHUNTHARAPAI, A MICHIEL, DF OPPENHEIM, JJ KELVIN, DJ TI INTERLEUKIN-8 RECEPTOR-BETA - THE ROLE OF THE CARBOXYL-TERMINUS IN SIGNAL-TRANSDUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN BETA-2-ADRENERGIC RECEPTOR; NEUTROPHIL-ACTIVATING PEPTIDE-2; GROWTH-STIMULATORY ACTIVITY; PROTEIN-COUPLED RECEPTORS; CHEMOTACTIC RECEPTOR; FUNCTIONAL EXPRESSION; AMINO TERMINUS; CLONING; LIGAND; IDENTIFICATION AB Two interleukin-8 (IL-8) receptors, alpha and beta, have been identified and cloned. Both receptors are thought to transduce signals by coupling to GTP-binding proteins. The aim of this study is to determine whether the carboxyl terminus (C') of IL-8 receptor beta (IL-8R beta) is involved in signaling in response to IL-8. We have constructed a number of IL-8R beta genes that encode truncated forms of the IL-8R beta. The deletions consisted of amino acids 349-355, 336-355, 325-355, and 317-355 (termed beta 2, beta 3, beta 4, and beta 5, respectively). 293 human embryonic kidney cells were transfected with the wild type IL-8R beta (beta 1) and with these mutants. Cells transfected with the mutated receptors expressed the receptors and bound IL-8 with the same high affinity as cells transfected with the wild type receptor. The capacity of the mutated receptors to convey functional signals was evaluated by comparing the chemotaxis index of cells expressing the C' truncated receptors to the index of cells expressing the wild type receptor. The results indicate that while cells expressing beta 1, beta 2, beta 3, and beta 4 were chemoattracted in response to IL-8, cells expressing beta 5 did not migrate in response to IL-8 stimulation. Therefore, the data suggest that amino acids 317-324 are involved in signaling by IL-8R beta. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NCI,BIOL RESPONSE MODIFIERS PROGRAM,PRECLIN EVALUAT LAB,FREDERICK,MD 21702. NCI,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. GENENTECH INC,S SAN FRANCISCO,CA 94080. RP BENBARUCH, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. NR 46 TC 72 Z9 72 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 APR 21 PY 1995 VL 270 IS 16 BP 9121 EP 9128 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900014 PM 7721826 ER PT J AU ZOLKIEWSKA, A MOSS, J AF ZOLKIEWSKA, A MOSS, J TI PROCESSING OF ADP-RIBOSYLATED INTEGRIN ALPHA-7 IN SKELETAL-MUSCLE MYOTUBES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELLS; PROTEINS; GLYCOHYDROLASE; RECEPTOR; SURFACE; ANCHOR AB Integrin alpha 7 is a major substrate in skeletal muscle cells for the cell surface, glycosylphosphatidylinositol-anchored, arginine-specific ADP-ribosyltransferase. Since ADP-ribosylarginine hydrolase, the enzyme responsible for cleavage of the ADP-ribosylarginine bond and a component with the transferase of a putative ADP-ribosylation cycle, is cytosolic, the processing of ADP-ribosylated integrin alpha 7 was investigated. Following incubation of differentiated mouse C2C12 myoblasts with [adenylate-P-32]NAD and analysis by SDS-polyacrylamide gel electrophoresis under reducing conditions, two [P-32]ADP-ribosylated forms of integrin alpha 7 were resolved, By pulse chase and purification of the radio labeled proteins on a laminin affinity column, it was demonstrated that a 105-kDa ADP-ribosylated form originated from a mono ADP-ribosylated 102-kDa form and represented integrin alpha 7 modified at more than one site, The additional site(s) of modification, utilized at higher NAD concentrations, were located in the 63-kDa N-terminal segment of integrin alpha 7. Both [P-32]ADP-ribosylated integrins were loosely associated with the cytoskeleton, bound to laminin affinity columns, and immunoprecipitated with antibodies to integrin beta 1. P-32 label was rapidly removed from [P-32]ADP-ribosylated integrin alpha 7 at either site of modification, a process inhibited by free ADP-ribose or p-nitrophenylthymidine-5'-monophosphate, an alternative substrate of 5'-nucleotide phosphodiesterase. The processed integrin alpha 7 was unavailable for subsequent ADP-ribosylation, although the amount of surface integrin alpha 7 remained constant, During the processing, no loss of label was observed from integrin alpha 7 radiolabeled with [C-14]NAD, containing C-14 in the nicotinamide proximal ribose, consistent with degradation of the ADP-ribose moiety by a cell surface 5'-nucleotide phosphodiesterase, Thus, cell surface ADP-ribosylation, in contrast to intracellular ADP-ribosylation, is not readily reversed by ADP-ribosylarginine hydrolase and seems to operate outside the postulated ADP-ribosylation cycle. RP ZOLKIEWSKA, A (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,BLDG 10,RM 5N307,10 CTR RD,MSC 1434,BETHESDA,MD 20892, USA. NR 29 TC 49 Z9 51 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 APR 21 PY 1995 VL 270 IS 16 BP 9227 EP 9233 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900029 PM 7721841 ER PT J AU COLOGNATOPYKE, H OREAR, JJ YAMADA, Y CARBONETTO, S CHENG, YS YURCHENCO, PD AF COLOGNATOPYKE, H OREAR, JJ YAMADA, Y CARBONETTO, S CHENG, YS YURCHENCO, PD TI MAPPING OF NETWORK-FORMING, HEPARIN-BINDING, AND ALPHA-1-BETA-1 INTEGRIN-RECOGNITION SITES WITHIN THE ALPHA-CHAIN SHORT ARM OF LAMININ-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEIN; MEDIATE CELL ATTACHMENT; NEURITE OUTGROWTH; GLOBULAR DOMAIN; CALCIUM-BINDING; LONG-ARM; MULTIDOMAIN PROTEIN; COLLAGEN RECEPTOR; NIDOGEN COMPLEX; B1 CHAIN AB Cell-interactive and architecture-forming functions are associated with the short arms of basement membrane laminin-1. To map and characterize these functions, we expressed recombinant mouse laminin-1 alpha-chain extending from the N terminus through one third of domain IIIb. This dumbbell-shaped glycoprotein (r alpha 1(VI-IVb)'), secreted by mammalian cells, was found to possess three activities. 1) Laminin polymerization was quantitatively inhibited by recombinant protein, supporting an alpha-chain role for a three-short arm interaction model of laminin self-assembly. 2) r alpha 1(VI IVb)' bound to heparin, and the activity was localized to a subfragment corresponding to domain VI by I-125-heparin blotting. 3) PC12 rat pheochromocytoma cells adhered to, and rapidly extended branching neurites on, r alpha 1(VI-IVb)', with adhesion inhibited by alpha 1 and beta 1 integrin chain-specific antibodies. The ability of anti-laminin antibody to block PC12 cell adhesion to laminin was selectively prevented by absorption with r alpha 1(VI-IVb)' or alpha-chain domain VI fragment. This active integrin-recognition site could furthermore be distinguished from a second cryptic alpha 1 beta 1-binding site exposed by heat treatment of fragment P1', a short arm fragment lacking globules. Thus, a polymer-forming, a heparin-binding, and the active alpha 1 beta 1 integrin-recognition site are all clustered at the end of the alpha-chain short arm, the latter two resident solely in domain VI. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PATHOL,PISCATAWAY,NJ 08854. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MICROBIOL & MOLEC GENET,PISCATAWAY,NJ 08854. NIDR,BETHESDA,MD 20892. MCGILL UNIV,CTR RES NEUROSCI,MONTREAL,PQ H3A 2B2,CANADA. FU NIDDK NIH HHS [R01 DK036425, R01-DK36425] NR 54 TC 101 Z9 101 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 1995 VL 270 IS 16 BP 9398 EP 9406 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900053 PM 7721864 ER PT J AU STANFORD, CM JACOBSON, PA EANES, ED LEMBKE, LA MIDURA, RJ AF STANFORD, CM JACOBSON, PA EANES, ED LEMBKE, LA MIDURA, RJ TI RAPIDLY FORMING APATITIC MINERAL IN AN OSTEOBLASTIC CELL-LINE (UMR-106-01 BSP) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOGENIC-SARCOMA CELLS; NODULES FORMED INVITRO; BONE SIALOPROTEIN BSP; PARATHYROID-HORMONE; BETA-GLYCEROPHOSPHATE; ALKALINE-PHOSPHATASE; BREFELDIN-A; INORGANIC PYROPHOSPHATE; X COLLAGEN; RAT AB This study evaluated a rapid biomineralization phenomenon exhibited by an osteoblastic cell line, UMR 106-01 BSP, when treated with either organic phosphates [beta-glycerophosphate (beta-GP), Ser-P, or Thr-P], inorganic phosphate (P-i), or calcium. In a dose-dependent manner, these agents (2-10 mM) stimulated confluent cultures to deposit mineral in the cell layer (ED(50) of similar to 4.6 mM for beta-GP (30 +/- 2 nmol Ca2+/mu g DNA) and similar to 3.8 mM (29 +/- 2 nmol Ca2+/mu g DNA) for P-i) with a plateau in mineral formation by 20 h (ET(50) approximate to 12-15 h). beta-GP or P-i treatment yielded mineral crystals having an x-ray diffraction pattern similar to normal human bone, Alizarin red-S histology demonstrated calcium mineral deposition in the extracellular matrix and what appeared to be intracellular paranuclear staining. Electron microscopy revealed small, needle-like crystals associated with fibrillar, extracellular matrix deposits and intracellular spherical structures. Mineral formation was inhibited by levamisole (ED(50) approximate to 250 mu M), pyrophosphate (ED(50) approximate to 1-10 mu M), actinomycin C-1 (500 ng/ml), cycloheximide (50 mu g/ml), or brefeldin A (1 mu g/ml). These results indicate that UMR 106-01 BSP cells form a bio apatitic mineralized matrix upon addition of supplemental phosphate. This process involves alkaline phosphatase activity, ongoing RNA and protein synthesis, as well as Golgi-mediated processing and secretion. C1 UNIV IOWA,COLL DENT,DOW INST DENT RES,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT ORTHOPAED SURG,IOWA CITY,IA 52242. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [2 SO7 RR05313-31]; NIAMS NIH HHS [AR-0705] NR 57 TC 307 Z9 309 U1 4 U2 31 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 APR 21 PY 1995 VL 270 IS 16 BP 9420 EP 9428 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900056 PM 7721867 ER PT J AU KLEIN, HG DUVERGER, N ALBERS, JJ MARCOVINA, S BREWER, HB SANTAMARINAFOJO, S AF KLEIN, HG DUVERGER, N ALBERS, JJ MARCOVINA, S BREWER, HB SANTAMARINAFOJO, S TI IN-VITRO EXPRESSION OF STRUCTURAL DEFECTS IN THE LECITHIN-CHOLESTEROL ACYLTRANSFERASE GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FISH EYE DISEASE; SITE-DIRECTED MUTAGENESIS; DIFFERENT ALLELIC MUTATIONS; HIGH-DENSITY-LIPOPROTEIN; AMINO-ACID EXCHANGE; LCAT DEFICIENCY; SECONDARY STRUCTURE; FAMILIAL LECITHIN; MOLECULAR DEFECT; ESTERIFICATION RATE AB Classic LCAT deficiency (CLD) and fish eye disease (FED) are two clinically distinct syndromes, associated with defects in the lecithin-cholesterol acyltransferase (LCAT) gene resulting in total (CLD) or partial (FED) enzyme deficiency. In order to investigate the underlying molecular mechanisms that lead to different phenotypic expression in CLD and FED, LCAT mutants associated with either CLD (LCAT(147), LCAT(156), and LCAT(228)) or FED (LCAT(10), LCAT(123), LCAT(158), LCAT(293), LCAT(300), and LCAT(347)) were expressed in vitro in human embryonic kidney 293 cells and characterized with respect to LCAT expression and enzyme activity, Evaluation of mutant LCAT gene transcription by Northern blot analysis demonstrated LCAT mRNA of normal size and concentration. Although all constructs gave rise to similar intracellular LCAT mass, the amount of enzyme present in the media for LCAT(147), LCAT(156),and LCAT(300) was reduced to less than 10% of normal, suggesting that these mutations disrupted LCAT secretion. Western blot analysis of cell culture media containing wild type or mutant LCAT demonstrated the presence of a single normal-sized band of 67 kDa. The ability of the different enzymes to esterify free cholesterol in high density lipoprotein-like proteoliposomes (alpha-LCAT-specific activity) was reduced to less than 5% of normal for CLD mutants LCAT(147) and LCAT(228) and FED mutants LCAT(10) LCAT(123), LCAT(293), and LCAT(347), whereas that of LCAT(156), LCAT(158), and LCAT(300) ranged from 45 to 110% LCAT of control. Although most FED mutant LCAT enzymes retained the ability to esterify free cholesterol present in alpha- and beta-lipoproteins of heat-inactivated plasma, esterification was undetectable in all CLD mutants (LCAT(147), LCAT(156), and LCAT(228)). In contrast, all mutant enzymes retained the ability to hydrolyze the water soluble, short-chained fatty acid substrate p-nitrophenol-butyrate, In summary, our studies establish the functional significance of nine LCAT gene defects associated with either FED or CLD. Characterization of the expressed LCAT mutants identified multiple, overlapping functional abnormalities that include defects in secretion and/or disruption of enzymic activity. All nine LCAT mutants retained the ability to hydrolyze the water-soluble PNPB substrate, indicating intact hydrolytic function, Based on these studies we propose that mutations in LCAT residues 147, 156, 228 (CLD) and 10, 123, 158, 293, 300, and 347 (FED) do not disrupt the functional domain mediating LCAT phospholipase activity, but alter structural domains involved in lipid binding or transesterification. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,NW LIPID RES CTR,DEPT MED,SEATTLE,WA 98103. FU NHLBI NIH HHS [HL 3-00H6] NR 44 TC 21 Z9 22 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 APR 21 PY 1995 VL 270 IS 16 BP 9443 EP 9447 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900059 PM 7721870 ER PT J AU MICHELOTTI, EF TOMONAGA, T KRUTZSCH, H LEVENS, D AF MICHELOTTI, EF TOMONAGA, T KRUTZSCH, H LEVENS, D TI CELLULAR NUCLEIC-ACID BINDING-PROTEIN REGULATES THE CT ELEMENT OF THE HUMAN C-MYC PROTOONCOGENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUCINE ZIPPER PROTEIN; CHROMATIN STRUCTURE; GROWTH-FACTOR; K-PROTEIN; GENE; EXPRESSION; TRANSCRIPTION; RIBONUCLEOPROTEIN; REGION; CELLS AB The CT element of the c-myc gene is required for promoter P1 usage and can drive expression of a heterologous promoter, Both double strand (Sp1) and single strand (hnRNP K) CT-binding proteins have been implicated as mediators of CT action, Although significant levels of CT activity persisted following Sp1 immunodepletion, EGTA totally abolished transactivation, thus implicating another metal requiring factor in CT element activity, As hnRNP K binds to one strand of the CT element, but has no metal requirement, the opposite (purine-rich strand) was examined as a target for a met al-dependent protein, A zinc-requiring purine strand binding activity was identified as cellular nucleic acid binding protein (CNBP), a protein previously implicated in the regulation of sterol responsive genes. Two forms of CNBP differed in their relative binding to the CT- or sterol-response elements, CNBP was shown to be a bona fide regulator of the CT element by cotransfection of a CNBP expression vector that stimulated expression of a CT-driven but not an AP1-dependent reporter. These data suggest that hnRNP K and CNBP bind to opposite strands and co-regulate the CT element. C1 NCI,DEPT PATHOL,PATHOL LAB,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 29 TC 188 Z9 188 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 1995 VL 270 IS 16 BP 9494 EP 9499 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900066 PM 7721877 ER PT J AU MALABARBA, MG KIRKEN, RA RUI, H KOETTNITZ, K KAWAMURA, M OSHEA, JJ KALTHOFF, FS FARRAR, WL AF MALABARBA, MG KIRKEN, RA RUI, H KOETTNITZ, K KAWAMURA, M OSHEA, JJ KALTHOFF, FS FARRAR, WL TI ACTIVATION OF JAR3, BUT NOT JAK1, IS CRITICAL TO INTERLEUKIN-4 (IL4) STIMULATED PROLIFERATION AND REQUIRES A MEMBRANE-PROXIMAL REGION OF IL4 RECEPTOR-ALPHA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA SIGNAL-TRANSDUCTION; NATURAL-KILLER-CELLS; TYROSINE KINASE; FUNCTIONAL COMPONENT; CHAIN; IL-2; LINE; IDENTIFICATION AB The tyrosine kinases JAK1 and JARS have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3 to a larger extent than JAK1, based upon three different evaluation criteria. These include a more vigorous tyrosine phosphorylation of JAK3 as measured by anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as determined by in vitro tyrosine kinase assays and a more manifest presence of JAK3 in activated IL4-receptor complexes. These observations suggest that IL4 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells, robust IL4-induced proliferation and JAK3 activation occurred without detectable involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a subordinate role in IL4 receptor signaling, and that in certain cells exclusive JARS activation may mediate IL4-induced cell growth. Moreover, mutational analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region was critical for JARS activation, while the I4R motif was not, which is compatible with a role of JARS upstream of the recruitment of the insulin receptor substrate-1/4PS signaling proteins by IL4 receptors. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. SANDOZ GMBH,RES INST,A-1235 VIENNA,AUSTRIA. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP MALABARBA, MG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 FU FIC NIH HHS [5FO5 TWO4300-02] NR 37 TC 55 Z9 56 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 APR 21 PY 1995 VL 270 IS 16 BP 9630 EP 9637 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900084 PM 7721895 ER PT J AU LIN, SL TSAI, CJ NUSSINOV, R AF LIN, SL TSAI, CJ NUSSINOV, R TI A STUDY OF 4-HELIX BUNDLES - INVESTIGATING PROTEIN-FOLDING VIA SIMILAR ARCHITECTURAL MOTIFS IN PROTEIN CORES AND IN SUBUNIT INTERFACES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE 4-HELIX BUNDLE; ARCHITECTURAL MOTIF; SUBUNIT INTERFACE; PROTEIN CORE; PROTEIN FOLDING ID CRYSTAL-STRUCTURE; 1.9-A RESOLUTION; DEHYDROGENASE; REFINEMENT; PACKING AB Four-helix bundles are identified and characterized in the subunit interfaces of protein multimers. We find that this motif occurs as often in the interfaces as in the protein monomers. Common and different characteristics demonstrated by the bundles in the two environments suggest the possible stabilization mechanisms of the bundles via cooperative helical twist, dipole alignment and interhelical connections. Nucleation of parallel helix pairs may be a favourable pathway before the pairs couple into bundles during folding. Certain properties found chaotic in the interface four-helix bundles indicate that either the subunit association is far from the global minimum conformation, or that the footprints of the folding pathway are recorded in these properties. C1 TEL AVIV UNIV,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES FACIL,PRI DYNACORP,MATH BIOL LAB,FREDERICK,MD 21702. RP LIN, SL (reprint author), NCI,FREDERICK CANC RES FACIL,MATH BIOL LAB,BLDG 469,RM 151,FREDERICK,MD 21702, USA. FU NCI NIH HHS [1-CO-74102] NR 27 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 21 PY 1995 VL 248 IS 1 BP 151 EP 161 DI 10.1006/jmbi.1995.0208 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU299 UT WOS:A1995QU29900011 PM 7731040 ER PT J AU YE, B BURKE, TR AF YE, B BURKE, TR TI A CONCISE SYNTHESIS OF THE DIFFERENTIATING ANTIBIOTIC L-AZATYROSINE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note ID SERINE; ACIDS C1 NCI,DCT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 14 TC 33 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 21 PY 1995 VL 60 IS 8 BP 2640 EP 2641 DI 10.1021/jo00113a056 PG 2 WC Chemistry, Organic SC Chemistry GA QV033 UT WOS:A1995QV03300056 ER PT J AU HEINRICHS, C MUNSON, PJ COUNTS, DR CUTLER, GB BARON, J AF HEINRICHS, C MUNSON, PJ COUNTS, DR CUTLER, GB BARON, J TI PATTERNS OF HUMAN GROWTH SO SCIENCE LA English DT Article ID LONGITUDINAL BONE-GROWTH; RAT C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,ANALYT BIOSTAT SECT,BETHESDA,MD 20892. RP HEINRICHS, C (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 14 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 21 PY 1995 VL 268 IS 5209 BP 442 EP 445 DI 10.1126/science.7716552 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QU572 UT WOS:A1995QU57200048 PM 7716552 ER PT J AU ANGERMANSTEWART, JA ELING, TE GLASGOW, WC AF ANGERMANSTEWART, JA ELING, TE GLASGOW, WC TI PROSTAGLANDIN-H SYNTHASE-2 IS INDUCED IN SYRIAN-HAMSTER EMBRYO CELLS IN RESPONSE TO BASIC FIBROBLAST GROWTH-FACTOR SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SWISS 3T3 CELLS; ARACHIDONIC-ACID METABOLISM; KINASE-C ACTIVATION; MITOGENIC RESPONSE; ENDOTHELIAL-CELLS; MESSENGER-RNA; SIGNAL TRANSDUCTION; INDUCIBLE CYCLOOXYGENASE; CELLULAR CYCLOOXYGENASE; LINOLEIC-ACID AB Metabolites of arachidonic acid and linoleic, acid can serve as regulators of the epidermal growth factor signal transduction system in Syrian hamster embryo (SHE) fibroblasts, We have now investigated the possible role of these lipids in modulating the signal transduction of basic fibroblast growth factor (bFGF), a potent mitogen to SHE fibroblasts, The addition of bFGF (0.1 to 1.0 ng/ml) to serum-deprived SHE cells stimulated a six- to sevenfold increase in the incorporation of thymidine into DNA. Structural analysis indicated that bFGF stimulated the metabolism of exogenous and endogenous arachidonic acid to primarily PGE(2), PGF(2 alpha), and PGD(2), with lesser amounts of uncharacterized prostaglandins observed. The metabolism of linoleic acid in SHE cells was not affected by bFGF. bFGF stimulated the expression of the inducible form of prostaglandin H synthase (PGHS-2) as determined by Northern analysis using murine PGHS-2 cDNA as the probe. PGHS-2 protein in the SHE cells was also increased by bFGF as determined by Western analysis using antibodies specific for PGHS-2. Levels of the constitutive (PGHS-1) enzyme and mRNA were not altered by bFGF. Preincubation of the cells with 1-2 mu M dexamethasone significantly inhibited bFGF-stimulated expression of PGHS-2 protein and mRNA. Dexamethasone potently inhibited bFGF induced mitogenesis in these cells. Pretreatment of SHE cells with indomethacin inhibited bFGF-dependent mitogenesis, sis well as endogenously produced PGE(2). The data suggests that regulation of PGHS-2 expression may be an element of the bFGF mitogenic signal transduction pathway. (C) 1995 Academic Press, Inc. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 58 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 20 PY 1995 VL 318 IS 2 BP 378 EP 386 DI 10.1006/abbi.1995.1243 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV624 UT WOS:A1995QV62400017 PM 7733666 ER PT J AU SAHAKIAN, JA SZWEDA, LI FRIGUET, B KITANI, K LEVINE, RL AF SAHAKIAN, JA SZWEDA, LI FRIGUET, B KITANI, K LEVINE, RL TI AGING OF THE LIVER - PROTEOLYSIS OF OXIDATIVELY MODIFIED GLUTAMINE-SYNTHETASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MIXED-FUNCTION OXIDATION; METAL-CATALYZED OXIDATION; AGE-RELATED-CHANGES; PROTEIN OXIDATION; ESCHERICHIA-COLI; CYSTEINE PROTEINASE; RATS; DEGRADATION; TURNOVER; ENZYMES AB During aging cells accumulate altered forms of proteins, notably oxidatively modified proteins. The multicatalytic protease selectively degrades oxidized proteins, suggesting that the age-related accumulation of oxidized proteins might be a consequence of decreased activity of this protease, The protease activity of liver homogenates was assayed with an improved fluorimetric method, using oxidatively modified glutamine synthetase as substrate, Application of this assay to extracts from liver of Fischer 344 rats from both Japan and the United States demonstrated a marked preference for the oxidized substrate, as expected. Extracts from animals ages 8 to 26 months maintain both total proteolytic activity and the ability to distinguish between native and oxidized substrates. Oxidatively modified hepatocyte extracts were also employed as substrate, and older animals again maintained proteolytic activity. The multicatalytic protease was purified from liver of young and old rats, and the specific activity of the preparations were comparable when assayed with oxidatively modified glutamine synthetase. We conclude that the intrinsic neutral or alkaline proteolytic activity of rat liver is maintained during aging, C1 UNIV TOKYO,FAC MED,RADIOISOTOPE RES INST,TOKYO 113,JAPAN. RP SAHAKIAN, JA (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 106,BETHESDA,MD 20892, USA. RI Levine, Rodney/D-9885-2011 NR 43 TC 44 Z9 46 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 20 PY 1995 VL 318 IS 2 BP 411 EP 417 DI 10.1006/abbi.1995.1248 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV624 UT WOS:A1995QV62400022 PM 7733671 ER PT J AU MISIK, V KIRSCHENBAUM, LJ RIESZ, P AF MISIK, V KIRSCHENBAUM, LJ RIESZ, P TI FREE-RADICAL PRODUCTION BY SONOLYSIS OF AQUEOUS MIXTURES OF N,N-DIMETHYLFORMAMIDE - AN EPR SPIN-TRAPPING STUDY SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID WATER MIXTURES; SONOCHEMISTRY; ULTRASOUND; PYROLYSIS; CAVITATION AB The 50-kHz sonochemistry of argon-saturated aqueous mixtures of N,N-dimethylformamide (DMF) was investigated by spin trapping with EPR detection, using 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) as the spin trap. Methyl radicals, produced by pyrolysis in the hot cavitation regions and (CH2N)-C-.(CH3)CHO radicals, formed by hydrogen abstraction from DMF, were spin trapped over a wide range of DMF concentrations (0.004-12.9 mol/L (100% DMF)). The thermal decomposition of the spin trap did not contribute to the observed radical yield. Sonochemical yields of both types of radical adducts increased with increasing DMF concentration in spite of the decreased production of H-. and (OH)-O-. radicals from the thermolysis of water. The increase of the radical yield is not due to the increased availability of the monomeric form of the spin trap at higher DMF concentrations but can be explained by an increased amount of DMF thermolysis in the hot cavitation region. This behavior is in contrast to that of aqueous mixtures of volatile solvents (solvents with vapor pressures higher than water), which show a maximum followed by a decrease of radical yields at higher mole fractions of the volatile component, due to the decrease of the effective gamma = C-p/C-v in the imploding cavitation bubbles. C1 NCI, RADIAT BIOL BRANCH, BETHESDA, MD 20892 USA. UNIV RHODE ISL, DEPT CHEM, KINGSTON, RI 02881 USA. NR 35 TC 24 Z9 24 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD APR 20 PY 1995 VL 99 IS 16 BP 5970 EP 5976 DI 10.1021/j100016a037 PG 7 WC Chemistry, Physical SC Chemistry GA QU828 UT WOS:A1995QU82800037 ER PT J AU REX, JH BENNETT, JE SUGAR, AM AF REX, JH BENNETT, JE SUGAR, AM TI THE TREATMENT OF CANDIDEMIA - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIAID,BETHESDA,MD 20892. BOSTON UNIV,MED CTR HOSP,BOSTON,MA 02118. RP REX, JH (reprint author), UNIV TEXAS,SCH MED,HOUSTON,TX 77030, USA. NR 5 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 APR 20 PY 1995 VL 332 IS 16 BP 1101 EP 1102 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QT187 UT WOS:A1995QT18700022 ER PT J AU KARLSSON, T ZHOU, SY LANDGREN, E LAVERGNE, C DIFIORE, PP ANAFI, M PAWSON, T CANTLEY, LC CLAESSONWELSH, L WELSH, M AF KARLSSON, T ZHOU, SY LANDGREN, E LAVERGNE, C DIFIORE, PP ANAFI, M PAWSON, T CANTLEY, LC CLAESSONWELSH, L WELSH, M TI MOLECULAR-INTERACTIONS OF THE SRC HOMOLOGY-2 DOMAIN PROTEIN SHB WITH PHOSPHOTYROSINE RESIDUES, TYROSINE KINASE RECEPTORS AND SRC HOMOLOGY-3 DOMAIN PROTEINS SO ONCOGENE LA English DT Article DE SRC HOMOLOGY 2 (SH2) DOMAIN; SRC HOMOLOGY 3 (SH3) DOMAIN; TYROSINE KINASE RECEPTORS; PROLINE-RICH MOTIFS; MITOGENIC SIGNAL TRANSDUCTION; ADAPTER SH2 DOMAIN PROTEIN ID GROWTH-FACTOR RECEPTOR; PDGF BETA-RECEPTOR; SIGNAL TRANSDUCTION; AUTOPHOSPHORYLATION SITES; POINT MUTATION; C-SRC; RAS; IDENTIFICATION; GRB2; ASSOCIATION AB The molecular interactions of the Src homology 2 (SH2) domain and the N-terminal proline-rich sequence motifs (pro-1 to pro-5) of the SH2 protein Shb with other components were presently characterised, Using a degenerate phosphopeptide library the preferred binding site for the Shb SH2 domain was determined to pTyr-Thr/Val/Ile-X-Leu at positions +1 to +3 relative the phosphotyrosine residue, Experiments with competing peptides and platelet-derived growth factor (PDGF) beta-receptor mutants with Y to F substitutions in autophosphorylation sites revealed multiple binding sites for the Shb SH2 domain in the receptor, The Shb SH2 domain also binds to in vitro phosphorylated fibroblast growth factor receptor-1 (FGFR-1) mainly through position Y776, The receptor experiments suggest that other residues besides the +1 to +3 positions may also be of significance for Shb binding, The pro-4/pro-5 motif of Shb binds in vitro particularly well to the Src, p85 alpha PI3-kinase and Eps8 SH3 domains expressed as GST fusion proteins, However, the GST-SH3 domain fusion proteins tested bind in vitro to peptides corresponding to the pro-1 to pro-5 motifs of Shb with low affinity and selectivity, suggesting that sequences outside the core proline motif may also be important for Shb-SH3 domain interactions, In vivo association between Shb-SH3 domain proteins v-Src and Eps8 was detected by coimmunoprecipitation. PDGF treatment did not affect the association between Eps8 and Shb. The data suggest that Shb is an adaptor protein linking SH3 domain proteins to tyrosine kinases or other tyrosine phosphorylated proteins. C1 UNIV UPPSALA,DEPT MED CELL BIOL,UPPSALA,SWEDEN. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV SIGNAL TRANSDUCT,BOSTON,MA. UPPSALA UNIV,LUDWIG INST CANC RES,UPPSALA,SWEDEN. HOP ROBERT DEBRE,INSERM,CJF 93-13,F-75019 PARIS,FRANCE. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO,ON M5G 1X5,CANADA. RI Di Fiore, Pier Paolo/K-2130-2012; Pawson, Tony/E-4578-2013; Cantley, Lewis/D-1800-2014 OI Di Fiore, Pier Paolo/0000-0002-2252-0950; Cantley, Lewis/0000-0002-1298-7653 NR 41 TC 53 Z9 56 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 20 PY 1995 VL 10 IS 8 BP 1475 EP 1483 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QU681 UT WOS:A1995QU68100002 PM 7537362 ER PT J AU LARMINAT, F BEECHAM, EJ LINK, CJ MAY, A BOHR, VA AF LARMINAT, F BEECHAM, EJ LINK, CJ MAY, A BOHR, VA TI DNA-REPAIR IN THE ENDOGENOUS AND EPISOMAL AMPLIFIED C-MYC ONCOGENE LOCI IN HUMAN TUMOR-CELLS SO ONCOGENE LA English DT Article DE DNA REPAIR; C-MYC ONCOGENE; DOUBLE-MINUTE CHROMOSOME ID COMPLEMENTATION GROUP-C; HOMOGENEOUSLY STAINING REGIONS; DIHYDROFOLATE-REDUCTASE GENE; HUMAN-COLON CARCINOMA; MATRIX ASSOCIATED DNA; ULTRAVIOLET-LIGHT; DOUBLE MINUTES; TRANSCRIPTION; AMPLIFICATION; FIBROBLASTS AB We have studied the repair of u.v.-induced cyclobutane pyrimidine diners (CPDs) in amplified c-myr: oncogene loci in human colon cancer cells to better understand the relationship between chromatin structure, transcription and DNA repair. To assess the variation in DNA repair in the same gene whether located in a chromosomal site or in a extra-chromosomal site, we have quantitated the efficiency of excision repair after u.v. exposure in the endogenous and episomal c-myc genes isolated from COLO320HSR and DM cells. In the HSR cells, c-myc is localized in a homogeneously staining region (HSR), and in the DM cells, the gene is localized in double minute chromosomes (DM). Our results indicate that the repair is less efficient in c-myc amplicons organized as double minute chromosomes than in the endogenous c-myc amplicons, The episomal gene is not repaired with the same efficiency as when it is intrachromosomal. This may reflect differences in chromatin structure. An advantage of this biological system is that the cells possess two different alleles of the c-myc gene, one that is active and another which is inactive. We have studied the relationship between DNA repair and transcriptional activity in the c-myc locus by measuring the efficiency of excision repair after u.v. exposure in the normal and rearranged alleles of the c-myc gene. Surprisingly, the c-myc gene is repaired with similar efficiency in the highly transcribed allele as in the poorly expressed allele. However, u.v. damage is selectively removed from the transcribed strand of the active c-myc allele, but DNA repair is not strand specific in the non-expressed c-myc allele. C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 36 TC 5 Z9 5 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 20 PY 1995 VL 10 IS 8 BP 1639 EP 1645 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QU681 UT WOS:A1995QU68100021 PM 7731719 ER PT J AU CHOI, KS KIM, SJ KIM, S AF CHOI, KS KIM, SJ KIM, S TI THE RETINOBLASTOMA GENE-PRODUCT NEGATIVELY REGULATES TRANSCRIPTIONAL ACTIVATION MEDIATED BY THE HUMAN CYTOMEGALOVIRUS IE2 PROTEIN SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; IMMEDIATE-EARLY PROTEINS; DNA-BINDING PROTEIN; EARLY REGION-2 GENE; C-FOS EXPRESSION; SUSCEPTIBILITY GENE; TRANS-ACTIVATION; EARLY PROMOTER; RB GENE AB The IE2 gene product of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell. It is a potent transcriptional activator of many viral and cellular promoters. We found that the retinoblastoma susceptibility gene product (Rb) dramatically suppressed this IE2 transactivation of various promoters. However, unlike another tumor suppressor protein, p53, Rb did not have any significant effect on basal levels of transcription, suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery. We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2. Our results suggest that Rb may regulate the life cycle of HCMV, which is endemic in the human population. Furthermore, these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis. (C) 1995 Academic Press, Inc. C1 SEOUL NATL UNIV,INST MOLEC BIOL & GENET,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,COLL NAT SCI,DEPT MICROBIOL,SEOUL 151742,SOUTH KOREA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 60 TC 31 Z9 31 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD APR 20 PY 1995 VL 208 IS 2 BP 450 EP 456 DI 10.1006/viro.1995.1175 PG 7 WC Virology SC Virology GA QZ400 UT WOS:A1995QZ40000005 PM 7747417 ER PT J AU CONNORS, M CROWE, JE FIRESTONE, CY MURPHY, BR COLLINS, PL AF CONNORS, M CROWE, JE FIRESTONE, CY MURPHY, BR COLLINS, PL TI A COLD-PASSAGED, ATTENUATED STRAIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS CONTAINS MUTATIONS IN THE F-GENES AND L-GENES SO VIROLOGY LA English DT Article ID NEUTRALIZING ANTIGENIC DOMAINS; COMPLETE NUCLEOTIDE-SEQUENCE; POLYMERASE L-GENE; G-PROTEIN; FUSION GLYCOPROTEINS; GENOMIC RNA; VACCINE; LIVE; RSV; IDENTIFICATION AB In previous studies, a mutant (cp-RSV) of the RSV A2 strain derived from 52 serial cold passages in bovine embryonic tissue culture was highly attenuated in seropositive adults and children but caused upper respiratory tract disease in seronegative infants. We investigated the generic basis for this attenuation phenotype by comparing the complete genomic RNA sequence of this virus with the published sequence of strain A2 as well as with that of its unattenuated wild-type parent (HEK-7) virus. RNA was extracted from virions grown in tissue culture, reverse transcribed, amplified by the polymerase chain reaction (PCR), cloned, and sequenced. Changes from the published A2 wild-type sequence were confirmed on independently derived cDNA clones and by direct sequencing of PCR fragments. The HEK-7 parent virus was then analyzed at these positions by direct sequencing of PCR fragments. Fifteen nucleotide differences between the published A2 wild-type virus and cp-RSV were found. None appeared to involve cis-acting RNA sequences. Of the 15 nucleotide differences, only 1 occurred outside a translational open reading frame (ORF), and 2 which did occur within ORFs were silent at the amino acid level. The remaining 12 nucleotide differences encoded amino acid changes. All 3 of the mutations which were silent at the amino acid level, and 8 of the 12 which resulted in amino acid differences, were also present in the HEK-7 parent virus and therefore were not changes acquired during the cold passages. Thus, the remaining 4 nucleotide differences and the attendant 4 amino acid changes are associated with the attenuation phenotype of the cp-RSV. Two of the changes occur in the F gene and two in the L gene. These results confirm the previously described RSV genomic sequence, provide the first sequence of a live attenuated RSV vaccine strain, provide the first sequence of an RSV strain which has been evaluated in chimpanzees and humans, and indicate that attenuation in humans of a pneumovirus can be associated with a relatively small number of nucleotide and amino acid changes. C1 NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 42 TC 40 Z9 52 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD APR 20 PY 1995 VL 208 IS 2 BP 478 EP 484 DI 10.1006/viro.1995.1178 PG 7 WC Virology SC Virology GA QZ400 UT WOS:A1995QZ40000008 PM 7747420 ER PT J AU KARASEV, AV BOYKO, VP GOWDA, S NIKOLAEVA, OV HILF, ME KOONIN, EV NIBLETT, CL CLINE, K GUMPF, DJ LEE, RF GARNSEY, SM LEWANDOWSKI, DJ DAWSON, WO AF KARASEV, AV BOYKO, VP GOWDA, S NIKOLAEVA, OV HILF, ME KOONIN, EV NIBLETT, CL CLINE, K GUMPF, DJ LEE, RF GARNSEY, SM LEWANDOWSKI, DJ DAWSON, WO TI COMPLETE SEQUENCE OF THE CITRUS TRISTEZA VIRUS-RNA GENOME SO VIROLOGY LA English DT Article ID BEET YELLOWS CLOSTEROVIRUS; DOUBLE-STRANDED RNAS; COAT PROTEIN GENE; PLANT-VIRUSES; TRANSLATION; CODE AB The sequence of the entire genome of citrus tristeza virus (CTV), Florida isolate T36, was completed. The 19,296-nt CTV genome encodes 12 open reading frames (ORFs) potentially coding for at least 17 protein products. The 5'-proximal ORF la starts at nucleotide 108 and encodes a large polyprotein with calculated MW of 349 kDa containing domains characteristic of (from 5' to 3') two papain-like proteases (P-PRO), a methyltransferase (MT), and a helicase (HEL). Alignment of the putative P-PRO sequences of CTV with the related proteases of beet yellows closterovirus (BYV) and potyviruses allowed the prediction of catalytic cysteine and histidine residues as well as two cleavage sites, namely Val-Gly/Gly for the 5' proximal P-PRO domain and Met-Gly/Gly for the 5' distal P-PRO domain. The autoproteolytic cleavage of the polyprotein at these sites would release two N-terminal leader proteins of 54 and 55 kDa, respectively, and a 240-kDa C-terminal fragment containing MT and HEL domains. The apparent duplication of the leader domain distinguishes CTV from BYV and accounts for most of the size increase in the ORF 1a product of CTV. The downstream ORF 1b encodes a 57-kDa putative RNA-dependent RNA polymerase (RdRp), which is probably expressed via a +1 ribosomal frameshift. Sequence analysis of the frameshift region suggests that this +1 frameshift probably occurs at a rare arginine codon CGG and that elements of the RNA secondary structure are unlikely to be involved in this process. The complete polyprotein resulting from this frameshift event has a calculated MW of 401 kDa and after cleavage of the two N-terminal leaders would yield a 292-kDa protein containing the MT, HEL, and RdRp domains. Phylogenetic analysis of the three replication-associated domains, MT, HEL, and RdRp, indicates that CTV and BYV form a separate closterovirus lineage within the alpha-like supergroup of positive-strand RNA viruses. Two gene blocks or modules can be easily identified in the CTV genome. The first includes the replicative MT, HEL, and RdRp genes and is conserved throughout the entire alpha-like superfamily. The second block consists of five ORFs, 3 to 7, conserved among closteroviruses, including genes for the CTV homolog of HSP70 proteins and a duplicate of the coat protein gene. The 3'-terminal ORFs 8 to 11 encode a putative RNA-binding protein (ORF 11), and three proteins with unknown functions; this gene array is poorly conserved among closteroviruses. The genomic double-stranded CTV RNA had an extra G at the 3' terminus of the minus strand and an extra U at the 3' terminus of the plus strand. (C) 1995 Academic Press, Inc. C1 UNIV FLORIDA,CTR CITRUS RES & EDUC,LAKE ALFRED,FL 33850. USDA ARS,HORT RES LAB,ORLANDO,FL 32803. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. UNIV FLORIDA,DEPT HORT SCI,GAINESVILLE,FL 32611. UNIV CALIF RIVERSIDE,DEPT PLANT PATHOL,RIVERSIDE,CA 92521. RI Cline, Kenneth/J-6238-2013 NR 48 TC 291 Z9 337 U1 1 U2 13 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD APR 20 PY 1995 VL 208 IS 2 BP 511 EP 520 DI 10.1006/viro.1995.1182 PG 10 WC Virology SC Virology GA QZ400 UT WOS:A1995QZ40000012 PM 7747424 ER PT J AU SARID, R GAZIT, A TRONICK, SR YANIV, A AF SARID, R GAZIT, A TRONICK, SR YANIV, A TI IDENTIFICATION OF SEQUENCES IN THE LONG TERMINAL REPEAT OF THE LYMPHOPROLIFERATIVE DISEASE VIRUS REQUIRED FOR EFFICIENT TRANSCRIPTION SO VIROLOGY LA English DT Note ID ROUS-SARCOMA VIRUS; NEGATIVE REGULATORY ELEMENT; INFECTIOUS-ANEMIA VIRUS; SERUM RESPONSE FACTOR; BINDING PROTEIN; C RETROVIRUS; DNA-BINDING; CHLORAMPHENICOL ACETYLTRANSFERASE; GENE-EXPRESSION; SIMIAN VIRUS-40 AB We analyzed the long terminal repeat (LTR) of the lymphoproliferative disease virus of turkeys for sequences that influence its promoter activity by using the chloramphenicol acety[transferase assay. A series of LTR deletion mutants and recombinants between LTR and simian virus 40 regulatory sequences were used for these studies. Through transfection experiments, we identified a negative regulatory element residing at the 5' end of the U3. The two imperfect direct repeats (DRs) located at nt -170 to -125 upstream of the RNA transcription site were identified as enhancer elements which could stimulate transcription of a heterologous promoter in an orientation independent manner. Specific interaction of nuclear factors with the DRs element was identified. The two DRs contain cArg motifs which are suggested to play a role in tissue specific expression of several cellular genes. (C) 1995 Academic Press, Inc. C1 TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN MICROBIOL, IL-69978 TEL AVIV, ISRAEL. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 55 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 20 PY 1995 VL 208 IS 2 BP 789 EP 794 DI 10.1006/viro.1995.1213 PG 6 WC Virology SC Virology GA QZ400 UT WOS:A1995QZ40000043 PM 7747452 ER PT J AU SAAH, AJ HOOVER, DR PENG, Y PHAIR, JP VISSCHER, B KINGSLEY, LA SCHRAGER, LK AF SAAH, AJ HOOVER, DR PENG, Y PHAIR, JP VISSCHER, B KINGSLEY, LA SCHRAGER, LK TI PREDICTORS FOR FAILURE OF PNEUMOCYSTIS-CARINII PNEUMONIA PROPHYLAXIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTICENTER AIDS COHORT; VIRUS HIV INFECTION; CULTURED LUNG-CELLS; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; CIGARETTE-SMOKING; SECONDARY PROPHYLAXIS; CONTROLLED TRIAL; HOMOSEXUAL MEN AB Objective.-To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis. Design.-Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200x10(9)/L (200/mu L). Main Outcome Measure.-Occurrence or recurrence of PCP. Results.-A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine-367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P=.19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050x10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P<.001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P=.01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure tie, a time-dependent risk ratio of 0.55; P=.03). Conclusions.-These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required. C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. NIAID,DIV AIDS,BETHESDA,MD 20892. RP SAAH, AJ (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,624 N BROADWAY,ROOM 896,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [UQI-AI-35039, UQI-AI-35042, UQI-AI-35043] NR 32 TC 78 Z9 78 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 APR 19 PY 1995 VL 273 IS 15 BP 1197 EP 1202 DI 10.1001/jama.273.15.1197 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QT100 UT WOS:A1995QT10000028 PM 7707627 ER PT J AU MOSCOW, JA JOHNSTON, PG COLE, D POPLACK, DG COWAN, KH AF MOSCOW, JA JOHNSTON, PG COLE, D POPLACK, DG COWAN, KH TI CHARACTERIZATION OF CROSS-RESISTANCE TO METHOTREXATE IN A HUMAN BREAST-CANCER CELL-LINE SELECTED FOR RESISTANCE TO MELPHALAN SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE METHOTREXATE; MELPHALAN; DRUG RESISTANCE; BREAST CANCER ID DIHYDROFOLATE-REDUCTASE; THYMIDYLATE SYNTHASE; TRANSPORT ROUTES; L1210 CELLS; WILD-TYPE; SENSITIVITY; BINDING; PHARMACOKINETICS; 5-FLUOROURACIL; POLYGLUTAMATES AB We have demonstrated previously decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan (MelR MCF-7). Cross-resistance studies of MelR MCF-7 cells revealed that this cell line was 6.7-fold cross-resistant to methotrexate, but only 2-fold resistant to trimetrexate. Methotrexate transport studies in MelR MCF-7 cells showed a 2-fold decrease in initial methotrexate uptake and a 2-fold decrease in the V-max for methotrexate uptake in the resistant cells. Methotrexate resistance in MelR MCF-7 cells was also associated with a decrease in non-effluxable methotrexate following incubation with radiolabeled drug for 24 hr. Characterization of intracellular methotrexate after accumulation for 24 hr demonstrated decreased levels of free methotrexate in MelR MCF-7 cells. Analysis of methotrexate polyglutamate formation in MelR MCF-7 cells indicated that the decrease in non-effluxable, non-protein-bound methotrexate was associated with a 3-fold decrease in higher order methotrexate polyglutamate formation. No difference was noted in folylpolyglutamate synthetase activity between the resistant and parental cell lines. Therefore, the observed decrease in methotrexate polyglutamate formation in MelR MCF-7 cells appeared to result from decreased availability of substrate. There was no evidence of any alteration in the amount of the catalytic activity of dihydrofolate reductase in MelR MCF-7 cells compared with parental MCF-7 (WT MCF-7) cells; moreover, the binding affinity of dihydrofolate reductase for methotrexate and the percentage of protein-bound methotrexate were similar in both cell lines. In addition, the total amounts of thymidylate synthase protein and thymidylate synthase catalytic activity in MelR MCF-7 cells were unchanged. Thus, acquired methotrexate resistance in MCF-7 cells selected for resistance to melphalan appears to result from down-regulation of methotrexate uptake. C1 NCI,NCI NAVY BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP MOSCOW, JA (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 34 TC 8 Z9 8 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 18 PY 1995 VL 49 IS 8 BP 1069 EP 1078 DI 10.1016/0006-2952(95)98503-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QV998 UT WOS:A1995QV99800007 PM 7748187 ER PT J AU MAZUMDER, A RAGHAVAN, K WEINSTEIN, J KOHN, KW POMMIER, Y AF MAZUMDER, A RAGHAVAN, K WEINSTEIN, J KOHN, KW POMMIER, Y TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE BY CURCUMIN SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE CURCUMIN; HUMAN IMMUNODEFICIENCY; VIRUS TYPE-1; INTEGRASE; INHIBITION; ANTIVIRAL; STRUCTURE-ACTIVITY ID HIV DNA; PROTEIN; INVITRO; CELLS AB Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1) integrase. Curcumin has an inhibitory concentration(50) (IC50) for strand transfer of 40 mu M. Inhibition of an integrase deletion mutant containing only amino acids 50-212 suggests that curcumin interacts with the integrase catalytic core. Two structural analogs, methyl cinnamate and chlorogenic acid, were inactive. Energy minimization studies suggest that the anti-integrase activity of curcumin could be due to an intramolecular stacking of two phenyl rings that brings the hydroxyl groups into close proximity. The present data suggest that HIV-1 integrase inhibition may contribute to the antiviral activity of curcumin. These observations suggest new strategies for antiviral drug development that could be based upon curcumin as a lead compound for the development of inhibitors of HIV-1 integrase. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 25 TC 213 Z9 227 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 18 PY 1995 VL 49 IS 8 BP 1165 EP 1170 DI 10.1016/0006-2952(95)98514-A PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QV998 UT WOS:A1995QV99800018 PM 7748198 ER PT J AU WINGFIELD, PT STAHL, SJ WILLIAMS, RW STEVEN, AC AF WINGFIELD, PT STAHL, SJ WILLIAMS, RW STEVEN, AC TI HEPATITIS CORE ANTIGEN PRODUCED IN ESCHERICHIA-COLI - SUBUNIT COMPOSITION, CONFORMATIONAL-ANALYSIS, AND IN-VITRO CAPSID ASSEMBLY SO BIOCHEMISTRY LA English DT Article ID B VIRUS CORE; PROTEIN SECONDARY STRUCTURE; CIRCULAR-DICHROISM; ELECTRON-MICROSCOPY; PARTICLES; DOMAIN; IMMUNOGENICITY; SEDIMENTATION; DISTRIBUTIONS; EXPRESSION AB The production and biochemical and physicochemical analysis are described of recombinant produced hepatitis B virus core antigen (HBcAg capsid) and the corresponding particle produced by a deletion mutant missing the C-terminal 39 residues (HBeAg). Conditions for producing HBeAg from HBcAg capsids by in vitro proteolysis are also described. The morphology and masses of these capsids were determined by scanning transmission electron microscopy. Both HBcAg and HBeAg capsids comprise two size classes that correspond to icosahedral lattices with triangulation numbers (T) of 3 and 4, containing 180 and 240 subunits per capsid, respectively: This dimorphism was confirmed by sedimentation equilibrium and sedimentation velocity measurements on a Beckman Optima XL-A analytical ultracentrifuge. More than 60% of HBcAg capsids were T = 4, whereas only 15-20% of HBeAg capsids were of this size class: the remainder, in each case, were T = 3. Circular dichroism and Raman spectroscopy were used to determine the overall secondary structures of HBcAg and HBeAg capsids. Both have high alpha-helical contents, implying that this capsid protein does not conform to the canonical beta-barrel motif seen for all plant and animal icosahedral viral capsids solved to date. We suggest that the C-terminal domain of HBcAg has a random coil conformation. In vitro dissociation of HBeAg capsids under relatively mild conditions yielded stable dimers. The reassociation of HBeAg dimers into capsids appears to be driven by hydrophobic processes at neutral pH. Capsid assembly is accompanied by little change in subunit conformation as judged by circular dichroism and fluorescence spectroscopy. The thermal stability of HBcAg capsids was compared calorimetrically with that of in vitro assembled HBeAg capsids. Both have melting temperatures >90 degrees C, implying that the C-terminal region makes Little difference to the thermal stability of HBcAg: nevertheless, we discuss its possible role in facilitating disassembly and the release of viral nucleic acid. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT BIOCHEM,BETHESDA,MD 20814. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP WINGFIELD, PT (reprint author), NIH,PROT EXPRESS LAB,OFF DIRECTORS,BLDG 6B,ROOM 1B130,BETHESDA,MD 20892, USA. NR 57 TC 146 Z9 150 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 18 PY 1995 VL 34 IS 15 BP 4919 EP 4932 DI 10.1021/bi00015a003 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU260 UT WOS:A1995QU26000003 PM 7711014 ER PT J AU GUO, JH WU, WX YUAN, ZY POST, K CROUCH, RJ LEVIN, JG AF GUO, JH WU, WX YUAN, ZY POST, K CROUCH, RJ LEVIN, JG TI DEFECTS IN PRIMER-TEMPLATE BINDING, PROCESSIVE DNA-SYNTHESIS, AND RNASE-H ACTIVITY ASSOCIATED WITH CHIMERIC REVERSE TRANSCRIPTASES HAVING THE MURINE LEUKEMIA-VIRUS POLYMERASE DOMAIN JOINED TO ESCHERICHIA-COLI RNASE-H SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 RIBONUCLEASE-H; POL GENE-PRODUCTS; LACKING RIBONUCLEASE; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; MUTATIONAL ANALYSIS; KINETIC-ANALYSIS; ENDONUCLEASE; EXPRESSION AB The RNase H domain of murine leukemia virus (MuLV) reverse transcriptase (RT) was replaced with Escherichia coli RNase H, and the effect on RNase H activity and processive DNA synthesis was studied, using RNA-DNA hybrids containing sequences from the MuLV polypurine tract (PPT). Two chimeric RTs, having the entire polymerase domain or all but the last 19 amino acids, were expressed. In both cases, these RTs made multiple cuts in PPT-containing substrates, whereas wild-type cleavages occurred primarily at sites consistent with the distance between the polymerase and RNase H active sites. Primer extension assays performed with the chimeric RTs, an RNase H-minus RT, and wild-type showed that the presence of a wild-type viral RNase H domain facilitates processive DNA synthesis. When wildtype RT was bound to primer-template, two retarded bands could be detected in band-shift assays. In the absence of primer extension, a high proportion of enzyme-bound primer-template was associated with the faster-migrating band, whereas with DNA synthesis, more of the bound radioactivity was in the supershifted complex. This suggests that the super-shifted complex contains the active form of RT. The mutant RTs were deficient in formation of this complex, but the chimeric RTs were somewhat less defective than the RNase H-minus mutant. Our results demonstrate that in the wild-type enzyme, the RNase H domain is required to stabilize the interaction between RT and primer-template. RP GUO, JH (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 71 TC 42 Z9 42 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 18 PY 1995 VL 34 IS 15 BP 5018 EP 5029 DI 10.1021/bi00015a013 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU260 UT WOS:A1995QU26000013 PM 7536033 ER PT J AU IWASAKI, M DARDEN, TA PEDERSEN, LG NEGISHI, M AF IWASAKI, M DARDEN, TA PEDERSEN, LG NEGISHI, M TI ALTERING THE REGIOSPECIFICITY OF ANDROSTENEDIONE HYDROXYLASE-ACTIVITY IN P450S-2A-4/5 BY A MUTATION OF THE RESIDUE AT POSITION-481 SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID; SUBSTRATE-SPECIFICITY; SPIN EQUILIBRIUM; MOUSE P450COH; PROTEINS; 15-ALPHA-HYDROXYLASE; 16-BETA-HYDROXYLASE; CYTOCHROME-P-450; DETERMINANT AB Mouse P450 2a-5 (coumarin 7-hydroxylase) acquires androstenedione (AD) hydroxylase activity by substituting Phe at position 209 with Asn. However, this mutant P450 2a-5 (F209N) and the corresponding mutant P450 2a-4 (L209N) exhibit different regiospecificites of androstenedione (AD) hydroxylase activity. While the former mutant catalyzes both AD 15 alpha- and 7 alpha-hydroxylase activities at similar rates, the latter mutant maintains the original high specificity of AD 15 alpha-hydroxylase activity. The AD hydroxylase activities in chimeric enzymes of the mutants L209N and F209N show that the regiospecificities are determined by the carboxy-terminal halves of the P450 molecules. Mutations at each of the four different residues within the carboxy-terminal halves indicate that the differences in regiospecificity are determined by the Val/Ala mutation at position 481. As the size of the hydrophobic amino acid at position 481 becomes larger (Ala < Val < Ile), the regiospecificities toward the C15 position of the AD molecule are dramatically increased. The regiospecificity is also increased by placing positively-charged Arg at position 481, although the remaining 15 alpha-hydroxylase activity in this mutant is considerably lower than the other P450s. The results indicate that the size of the residue at position 481 is a key factor in regulating the regiospecificity of AD hydroxylase activity in the P450s. Modeling AD in the substrate-heme pocket of bacterial P450 101A provided further support that residue 481 may reside near the steroid molecule so as to possibly affect the AD hydroxylase activity. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NIEHS,QUANTITAT & COMPUTAT BIOL LAB,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 32 TC 23 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 18 PY 1995 VL 34 IS 15 BP 5054 EP 5059 DI 10.1021/bi00015a016 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU260 UT WOS:A1995QU26000016 PM 7711025 ER PT J AU ALMOUZNI, G WOLFFE, AP AF ALMOUZNI, G WOLFFE, AP TI CONSTRAINTS ON TRANSCRIPTIONAL ACTIVATOR FUNCTION CONTRIBUTE TO TRANSCRIPTIONAL QUIESCENCE DURING EARLY XENOPUS EMBRYOGENESIS SO EMBO JOURNAL LA English DT Article DE MID-BLASTULA TRANSITION; QUIESCENCE; TRANSCRIPTION; XENOPUS ID RNA POLYMERASE-II; MAJOR DEVELOPMENTAL TRANSITION; TATA-BINDING PROTEIN; MIDBLASTULA TRANSITION; DNA-REPLICATION; HISTONE SYNTHESIS; CYTOMEGALO-VIRUS; CELL-CYCLE; INVITRO; CHROMATIN AB We have examined the cause of transcriptional quiescence prior to the mid-blastula transition (MBT) in Xenopus laevis. We have found distinct requirements for transcription of class II and class III genes. An artificial increase of the amount of DNA present within the embryo over that found at the MBT allows precocious transcription of tRNA genes, but not of the adenovirus E4 or human cytomegalovirus (CMV) promoters. Thus titration of an inhibitor by exogenous DNA determines class III but not class II gene activation. We demonstrate that the action of the inhibitor depends on the association of core histones with DNA. The addition of exogenous TBP, together with an increase in the amount of DNA within the embryo, allows significant basal transcription of class II genes prior to the MBT, whereas it does not increase transcription of tRNA genes. To examine the activation of transcription above basal levels, we used a defined minimal promoter containing five Gal4 binding sites and the activator Gal4-VP16. Precocious transcriptional activation is directed by Gal4-VP16 prior to the MBT, demonstrating that a functional transcriptional machinery exists at this early developmental stage. Furthermore, since this activation can occur in the absence of exogenous TBP or chromatin titration, a transcription factor that can penetrate chromatin is sufficient for recruitment of this machinery to a promoter. Our results support the hypothesis that the temporal regulation of transcription during early embryogenesis in Xenopus reflects not only a titration of inhibitors by DNA, but also a deficiency in the activity of transcriptional activators prior to the MBT. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 85 TC 65 Z9 65 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 APR 18 PY 1995 VL 14 IS 8 BP 1752 EP 1765 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QW905 UT WOS:A1995QW90500020 PM 7737126 ER PT J AU SHIRAKATA, M PATERSON, BM AF SHIRAKATA, M PATERSON, BM TI THE E12 INHIBITORY DOMAIN PREVENTS HOMODIMER FORMATION AND FACILITATES SELECTIVE HETERODIMERIZATION WITH THE MYOD FAMILY OF GENE REGULATORY FACTORS SO EMBO JOURNAL LA English DT Article DE BHLH TRANSCRIPTION FACTORS; E12 DIMERIZATION INHIBITORY DOMAIN; MRF-EL2 DIMERIZATION SPECIFICITY ID DNA-BINDING; LEUCINE ZIPPER; MYOGENIC CELLS; MUSCLE; PROTEIN; MYC; DIMERIZATION; MOTIF; SPECIFICITY; DISTINCT AB Although the ubiquitous helix-loop-helix (HLH) protein E12 does not homodimerize efficiently, the myogenic factor MyoD forms an avid DNA-binding heterodimer with E12 through the conserved HLH dimerization domain. However, the mechanism which ensures this selective dimerization is not understood at present. In our functional studies of various amino acid changes in the E12 HLH domain, we found that a single substitution in E12 helix 1 can abolish the effect of the E12 inhibitory domain and results in the efficient DNA binding of the E12 homodimer. Competition experiments revealed that the inhibitory domain, in fact, blocks the dimerization of E12 rather than DNA binding. MyoD contains two glutamic residues in helix 2 that are required for efficient dimerization with E12. More importantly, these residues were not essential for dimerization with E12 mutants in which the dimerization inhibitory domain had been relaxed, or for dimerization with E47 which does not contain the inhibitory domain owing to the use of an alternative exon. The positions of these glutamic residues are conserved among the four myogenic factors. Thus, members of the MyoD family of gene regulatory proteins can overcome the E12 dimerization inhibitory domain through a mechanism involving, in part, the negatively charged amino acid residues in helix 2. This result describes a novel mechanism facilitating the selective formation of the MyoD(MRF)-E12 heterodimer enhances that dimerization specificity and may apply to other members of the E-protein family. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 41 TC 20 Z9 21 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 APR 18 PY 1995 VL 14 IS 8 BP 1766 EP 1772 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QW905 UT WOS:A1995QW90500021 PM 7737127 ER PT J AU PANYUTIN, IG BISWAS, I HSIEH, P AF PANYUTIN, IG BISWAS, I HSIEH, P TI A PIVOTAL ROLE FOR THE STRUCTURE OF THE HOLLIDAY JUNCTION IN DNA BRANCH MIGRATION SO EMBO JOURNAL LA English DT Article DE BRANCH MIGRATION; HOLLIDAY JUNCTION; RECOMBINATION ID BACTERIOPHAGE-T7 ENDONUCLEASE-I; DIETHYL PYROCARBONATE; RESOLUTION; CRUCIFORM; CLEAVAGE; CATION; IONS AB Branch migration of a DNA Holliday junction is a key step in genetic recombination that affects the extent of transfer of genetic information between homologous DNA sequences. We previously observed that the rate of spontaneous branch migration is exceedingly sensitive to metal ions and postulated that. the structure of the cross-over point might be one critical determinant of the rate of branch migration. Other investigators have shown that in the presence of divalent metal ions like magnesium, the Holliday junction assumes a folded conformation in which base stacking is retained through the cross-over point. This base stacking is disrupted in the absence of magnesium. Here we measure the rate of branch migration as a function of Mg2+ concentration. The rate of branch migration increases dramatically at MgCl2 concentrations below 500 mu M, with the steepest acceleration occurring between 300 and 100 mu M MgCl2. This increase in the rate of branch migration coincides with the loss of base stacking in the four-way junction over this same interval of magnesium concentration, as measured by the susceptibility of junction residues to modification by osmium tetroxide and diethyl pyrocarbonate. We conclude that at physiological concentrations of intracellular Mg2+, base stacking in the Holliday junction constitutes one kinetic barrier to branch migration and that disruption of base stacking at the cross-over relieves this constraint. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 35 TC 73 Z9 74 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD APR 18 PY 1995 VL 14 IS 8 BP 1819 EP 1826 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QW905 UT WOS:A1995QW90500026 PM 7737132 ER PT J AU VANDENBRULE, FA BUICU, C BALDET, M SOBEL, ME COOPER, DNW MARSCHAL, P CASTRONOVO, V AF VANDENBRULE, FA BUICU, C BALDET, M SOBEL, ME COOPER, DNW MARSCHAL, P CASTRONOVO, V TI GALECTIN-1 MODULATES HUMAN-MELANOMA CELL-ADHESION TO LAMININ SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GALACTOSIDE-BINDING LECTIN; EXPRESSION; RECEPTOR; SECRETION; PROTEIN; PATHWAY; MUSCLE AB Galectins constitute a gene family of beta-galactoside-specific lectins that show high homology in their carbohydrate-binding site. They have been postulated to be involved in many biological events, but their specific functions are not yet well defined. Galectin-1 is a laminin binding protein that recognizes poly N-acetyllactosamine chains on this major basement membrane glycoprotein. In this study, we analyzed the possibility that galectin-1 could modulate interactions between human melanoma cells and laminin. We demonstrated that A375 and A2058 cell lines express galectin-1 both intracellularly and on the cell surface. in an in vitro assay, recombinant galectin-1 increased melanoma cell attachment to laminin in a dose-dependent manner. This effect was abolished by lactose. Anti-galectin-1 inhibited adhesion of melanoma cells to laminin in a However, neither galectin-1 nor anti-galectin-1 antibody affected melanoma cell spreading on laminin in vitro. These data indicate that galectin-1 might participate in melanoma cell adhesion to laminin and therefore could be a modulator of invasion and metastasis. (C) 1995 Academic Press, Inc. C1 NCI,PATHOL LAB,MOLEC PATHOL SECT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. RP VANDENBRULE, FA (reprint author), UNIV LIEGE,METASTASIS RES LAB,PATHOL B23,3RD FLOOR,B-4000 LIEGE 1,BELGIUM. FU NIAMS NIH HHS [1-R55-AR41459] NR 26 TC 101 Z9 102 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1995 VL 209 IS 2 BP 760 EP 767 DI 10.1006/bbrc.1995.1564 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QU100 UT WOS:A1995QU10000050 PM 7733948 ER PT J AU HEEMSKERK, FMJ SAAVEDRA, JM AF HEEMSKERK, FMJ SAAVEDRA, JM TI QUANTITATIVE AUTORADIOGRAPHY OF ANGIOTENSIN-II AT(2), RECEPTORS WITH [I-125] CGP 42112 SO BRAIN RESEARCH LA English DT Article DE ANGIOTENSIN II; AT(2) RECEPTOR; QUANTITATIVE AUTORADIOGRAPHY; CGP 42112; MEDIAL GENICULATE NUCLEUS; INFERIOR OLIVE; BRAIN DEVELOPMENT ID RAT-BRAIN; BIOCHEMICAL-CHARACTERIZATION; LIGAND-BINDING; SUBTYPES; EXPRESSION; DITHIOTHREITOL; HETEROGENEITY; ANTAGONISTS; SENSITIVITY; CGP-42112A AB Most radiolabeled ligands for angiotensin II (Ang II) receptors do not discriminate between the AT(1) and AT(2) receptor subtypes, which must be distinguished by displacement with selective AT(1) or AT(2) ligands. We compared [I-125]CGP 42112 with the non-selective agonist [I-125]Sar(1)Angiotensin II. We studied the inferior olive, medial geniculate nucleus and the adrenal medulla, areas rich in AT(2) receptors, using both ligands with quantitative autoradiography and membrane binding techniques. [I-125]CGP 42112 bound with high affinity (K-d = 0.07-0.3 nM, depending on the area studied). [I-125]CGP 42112 binding was selective for AT(2) receptors, as determined by lack of competition with the AT(1) ligand losartan, and competition by the AT(2) ligands PD 123177 and unlabeled CGP 42112 and the non-selective peptides Ang II and angiotensin III (Ang III). Using [I-125]CGP 42112 binding, we found the same order of potency: CGP 42112 > Ang II = Ang III > PD 123177 using both quantitative autoradiography or membrane binding methods. Our results demonstrate that [I-125]CGP 42112 is the most selective, highest affinity ligand available for AT(2) receptors. Because of these characteristics, and low non-specific binding, quantitative autoradiography with [I-125]CGp 42112 is the method of choice to selectively characterize AT(2) receptors, especially in tissues like the brain, with a highly heterogeneous distribution of receptor subtypes. RP HEEMSKERK, FMJ (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20982, USA. NR 32 TC 44 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 17 PY 1995 VL 677 IS 1 BP 29 EP 38 DI 10.1016/0006-8993(95)00092-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA QU285 UT WOS:A1995QU28500004 PM 7606467 ER PT J AU ZHANG, L KOKKONEN, G ROTH, GS AF ZHANG, L KOKKONEN, G ROTH, GS TI IDENTIFICATION OF NEURONAL PROGRAMMED CELL-DEATH IN-SITU IN THE STRIATUM OF NORMAL ADULT-RAT BRAIN AND ITS RELATIONSHIP TO NEURONAL DEATH DURING AGING SO BRAIN RESEARCH LA English DT Note DE PROGRAMMED CELL DEATH; STRIATUM; AGING ID NERVOUS-SYSTEM; ACID AB Apoptotic neurons have been identified in normal adult rat striatum by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling technique. This observation suggests that neuronal programmed cell death starts at an early stage of adult life and may contribute to the aging associated neuronal loss. In addition, the frequency of apoptotic cells was found to significantly increase in old rats, which implies that aging itself accelerates the process. RP ZHANG, L (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,GRC BLDG,RM 4E18,BALTIMORE,MD 21224, USA. NR 20 TC 43 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 17 PY 1995 VL 677 IS 1 BP 177 EP 179 DI 10.1016/0006-8993(95)00197-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA QU285 UT WOS:A1995QU28500022 PM 7606465 ER PT J AU MOULD, AP GARRATT, AN ASKARI, JA AKIYAMA, SK HUMPHRIES, MJ AF MOULD, AP GARRATT, AN ASKARI, JA AKIYAMA, SK HUMPHRIES, MJ TI IDENTIFICATION OF A NOVEL ANTI-INTEGRIN MONOCLONAL-ANTIBODY THAT RECOGNIZES A LIGAND-INDUCED BINDING-SITE EPITOPE ON THE BETA-1 SUBUNIT SO FEBS LETTERS LA English DT Article DE INTEGRIN; ACTIVATION; LIGAND BINDING; MONOCLONAL ANTIBODY; CONFORMATIONAL CHANGE ID HUMAN-PLASMA FIBRONECTIN; ENDOTHELIAL-CELLS; ADHESION; MATRIX; VLA; ALPHA-5-BETA-1; MODULATION; CONFORMERS; ATTACHMENT; FRAGMENTS AB Integrins are the major family of receptors involved in the adhesive interactions of cells with extracellular matrix macromolecules. Although it is known that integrins can exist in active or inactive states, the molecular mechanisms by which integrin activity is modulated are poorly understood, A novel anti-integrin monoclonal antibody, 12G10, that enhances alpha 5 beta 1-fibronectin interactions has been identified. 12G10 binds to the beta 1 subunit and appears to recognise a region of the subunit that contains the epitopes of several previously described activating or inhibitory monoclonal antibodies, However, unlike other activating anti-beta 1 antibodies, the binding of 12G10 to alpha 5 beta 1 is increased in the presence of ligands (fibronectin fragment or RGD peptide). This is the first report for the beta 1 integrin family of an antibody that recognises a Ligand-induced binding site, and further emphasises the functional importance of a specific region of the beta 1 subunit in regulating integrin-ligand interactions. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP MOULD, AP (reprint author), UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. RI Garratt, Alistair/D-9893-2013 OI Garratt, Alistair/0000-0001-9631-3041 FU Wellcome Trust NR 23 TC 108 Z9 110 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 1995 VL 363 IS 1-2 BP 118 EP 122 DI 10.1016/0014-5793(95)00301-O PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QU314 UT WOS:A1995QU31400028 PM 7537221 ER PT J AU LEVAVASSEUR, F BURBELO, PD CARIOU, S LIETARD, J YAMADA, Y CLEMENT, B AF LEVAVASSEUR, F BURBELO, PD CARIOU, S LIETARD, J YAMADA, Y CLEMENT, B TI NUCLEAR RECRUITMENT OF ALP145 SUBUNIT OF REPLICATION FACTOR-C IN THE EARLY G1-PHASE OF THE CELL-CYCLE IN FAZA-567 HEPATOMA-CELL LINE AND HEPATOCYTE PRIMARY CULTURES SO FEBS LETTERS LA English DT Article DE HEPATOCYTE; CELL CYCLE; REPLICATION FACTOR C; PROLIFERATING CELL NUCLEAR ANTIGEN ID DNA POLYMERASE-DELTA; ACCESSORY PROTEINS; ESCHERICHIA-COLI; RAT HEPATOCYTES; III HOLOENZYME; HELA-CELLS; ANTIGEN; ACTIVATOR-1; EXPRESSION; BACTERIOPHAGE-T4 AB Using a combination of immunoprecipitation and Western blotting with Faza 567 hepatoma cell extracts revealed that the large subunit of replication factor C (A1p145; mRFC140) was in a complex with proliferating cell nuclear antigen (PCNA). Western blotting showed that A1p145 was more abundant in nuclear extracts from butyrate-treated hepatoma cells which blocks the cells in the G1 phase of the cell cycle than from routinely cultured cells. Indirect immunoperoxidase analysis of G1 blocked Faza hepatoma cells localized A1p145 protein predominantly in the nucleoli. When hepatoma cells were stimulated to progress toward the S phase, A1p145 protein was then observed in both the cytoplasm and the nucleoplasm of these cells. Studies with early cultured normal hepatocytes which are progressing from G(0), towards G(1), also showed a nucleolus distribution for A1p145. This is the first demonstration in mammalian cells that the large subunit of replication factor C is associated with PCNA in the nucleus and that its distribution within cells changes during the cell cycle. C1 CHRU PONTCHAILLOU, INSERM, U49, UNITE RECH HEPATOL, F-35033 RENNES, FRANCE. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. RI Burbelo, Peter/B-1027-2009; Clement, Bruno/E-5546-2016 NR 32 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 1995 VL 363 IS 1-2 BP 132 EP 136 DI 10.1016/0014-5793(95)00305-S PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QU314 UT WOS:A1995QU31400031 PM 7729533 ER PT J AU WINSKY, L JACOBOWITZ, DM AF WINSKY, L JACOBOWITZ, DM TI EFFECTS OF UNILATERAL COCHLEA ABLATION ON THE DISTRIBUTION OF CALRETININ MESSENGER-RNA AND IMMUNOREACTIVITY IN THE GUINEA-PIG VENTRAL COCHLEAR NUCLEUS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE AUDITORY NERVE; AUDITORY PATHWAYS; CALCIUM-BINDING PROTEIN; CALBINDIN D-28K; SUPERIOR OLIVARY COMPLEX ID CALCIUM-BINDING PROTEIN; STEM AUDITORY NUCLEI; LATERAL GENICULATE-NUCLEUS; SENSORINEURAL HEARING-LOSS; AFFERENT INFLUENCES; IMMUNOHISTOCHEMICAL LOCALIZATION; DEHYDROGENASE ACTIVITY; RAPID CHANGES; RAT-BRAIN; INNER-EAR AB The predominantly neuronal, calcium-binding protein calretinin is highly expressed in the guinea pig auditory system. Within the ventral cochlear nucleus (VCN), calretinin-positive auditory nerve fibers terminate on many calretinin-containing bushy, octopus, and multipolar cells. The abundance of calretinin in the cochlear nucleus provides an ideal system for examining the effects of altered neuronal input on the expression of this calcium-binding protein. The present experiments examined the effects of unilateral cochlea ablation on calretinin immunoreactivity and mRNA levels in the VCN. Calretinin mRNA was labeled by in situ hybridization histochemistry using a radioactive oligonucleotide probe and was quantified by optical density measures on autoradiograms. Survival times of 1, 7, and 56 days postlesion were examined. The results revealed a consistent increase in calretinin mRNA in the rostral portion of the ipsilateral anterior VCN 1 day postlesion but no effect on calretinin mRNA in this region at 7 and 56 days postlesion. The intensity of immunohistochemical label was also increased at 1 and 7 days after surgery. In contrast, calretinin mRNA was not affected 1 day postlesion in the ipsilateral posterior VCN but was decreased at both 7 and 56 days postlesion. The decrease in calretinin mRNA in the posterior VCN at longer survival times was accompanied by decreased immunolabeling of fibers projecting from VCN cells to the superior olivary complex. These results suggest that calretinin gene expression is regulated in part by auditory nerve activity in some cochlear neurons but that additional factors related to the unique cellular milieu also control calretinin expression. (C) 1995 Wiley-Liss, Inc. RP WINSKY, L (reprint author), NIMH,BLDG 10,ROOM 3D-48,BETHESDA,MD 20892, USA. NR 50 TC 50 Z9 50 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 17 PY 1995 VL 354 IS 4 BP 564 EP 582 DI 10.1002/cne.903540407 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QP492 UT WOS:A1995QP49200006 PM 7608338 ER PT J AU RUSH, AJ LAUX, G GILES, DE JARRETT, RB WEISSENBURGER, J FELDMANKOFFLER, F STONE, L AF RUSH, AJ LAUX, G GILES, DE JARRETT, RB WEISSENBURGER, J FELDMANKOFFLER, F STONE, L TI CLINICAL CHARACTERISTICS OF OUTPATIENTS WITH CHRONIC MAJOR DEPRESSION SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE MAJOR DEPRESSION; CHRONIC DEPRESSION; CLINICAL CHARACTERISTIC; OUTPATIENT ID FOLLOW-UP; UNIPOLAR DEPRESSION; AFFECTIVE-DISORDERS; PROGNOSIS; RECOVERY; SUBTYPES; EPISODES; ILLNESS; HEALTH; LIFE AB A cross-sectional evaluation of 243 unipolar, nonpsychotic outpatients with major depression was conducted. All subjects were diagnosed by RDC with SADS-L structured interviews. Diagnoses included RDC primary/secondary, RDC endogenous/nonendogenous and Winokur's family-history subtypes. Symptom severity was assessed by the 17-item Hamilton Rating Scale for Depression. Chronic depression was defined as the current episode of major depression lasting at least 2 years, corresponding to DSM-III-R and -IV criteria. Patients with chronic depression (n = 64) were compared with those with nonchronic depression (n = 179). Chronicity was not related to gender, symptom severity, prior length of illness, age at onset of illness, RDC endogenaus/nonendogenous, RDC primary/secondary or Winokur's family-history subtypes. Those with chronic depression were older and had fewer major depressive episodes than the nonchronic group. That the chronic group had fewer total episodes of depression than the nonchronic group, but a similar age at onset, is consistent with the notion that patients in a current chronic episode have characteristically longer depressive episodes throughout the course of their illness. Those with chronic episodes may be subject to psychological, biological and/or sociocultural factors that preclude an earlier episode remission for these individuals. C1 UNIV TEXAS,SW MED CTR,MENTAL HLTH CLIN RES CTR,DALLAS,TX. UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. UNIV BONN,DEPT PSYCHIAT,W-5300 BONN,GERMANY. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA. WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA. TEL AVIV UNIV,SCH MED,IL-69978 TEL AVIV,ISRAEL. BEILINSON MED CTR,TEL AVIV,ISRAEL. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD. OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-38238, MH-35370, MH-41115] NR 52 TC 33 Z9 34 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect Disord. PD APR 16 PY 1995 VL 34 IS 1 BP 25 EP 32 DI 10.1016/0165-0327(94)00101-E PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QV752 UT WOS:A1995QV75200003 PM 7622736 ER PT J AU MAURER, MS SHEFRIN, EA FLEG, JL AF MAURER, MS SHEFRIN, EA FLEG, JL TI PREVALENCE AND PROGNOSTIC-SIGNIFICANCE OF EXERCISE-INDUCED SUPRAVENTRICULAR TACHYCARDIA IN APPARENTLY HEALTHY-VOLUNTEERS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONTRACTION-EXCITATION FEEDBACK; ARRHYTHMIAS AB The prevalence, characteristics, and prognostic significance of supraventricular tachycardia (SVT) occurring during maximal treadmill exercise testing were examined in 843 male and 540 female asymptomatic volunteers aged 20 to 94 years from the Baltimore Longitudinal Study of Aging who underwent exercise testing a mean of 2.3 times between 1977 and 1991, Exercise-induced SVT occurred during a) least 1 test in 51 men (6.0%) and 34 women (6.3%), p = NS for gender. The 85 subjects with exercise-induced SVT were significantly older than tile 1,298 free from this arrhythmia (66.0 +/- 13.5 vs 49.7 +/- 18.0 years, respectively, p < 0.001). The prevalence of SVT increased with age in men (p < 0.001) but not in women. Ninety-eight percent of the 141 discrete episodes of exercise-induced SVT were paroxysmal SVT, with heart rates varying from 105 to 290 beats/min (mean 186.3 +/- 43.3); only 16% were > 10 beats in duration and only 4% of subjects were symptomatic. Nearly half (44%) of SVT episodes occurred at peak effort. Coronary risk factors, echocardiographic left atrial size (3.3 +/- 6.7 vs 3.3 +/- 0.6 cm), and the prevalence of exercise-induced ischemic ST-segment depression (11% vs 13%) were similar in 85 subjects with SVT and 170 control subjects matched for age and sex, Although the incidence of cardiac events (angina pectoris, nonfatal myocardial infarction, cardiac syncope, and cardiac death) was not significantly different between subjects (6%) and control group (10%) over a mean follow-vp period of 5.7 +/- 3.9 years, 10% of subjects and 2% of controls subsequently developed atrial fibrillation or paroxysmal SVT, p < 0.05 by life-table analysis. Thus, exercise-induced SVT in apparently healthy volunteers is usually limited to short, asymptomatic runs occurring near peak exercise in predominantly older persons, is unassociated with standard coronary risk factors or exercise-induced myocardial ischemia, and does not portend increased cardiovascular mortality or coronary events, but does appear to predict a higher incidence of spontaneous supraventricular tachyarrhythmia over the next several years. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI & LONGITUDINAL STUDIES LAB,BALTIMORE,MD 21224. NR 18 TC 29 Z9 29 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1995 VL 75 IS 12 BP 788 EP 792 DI 10.1016/S0002-9149(99)80412-3 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QT062 UT WOS:A1995QT06200007 PM 7717280 ER PT J AU DOMANSKI, M ELLIS, S EAGLE, K AF DOMANSKI, M ELLIS, S EAGLE, K TI DOES PREOPERATIVE CORONARY REVASCULARIZATION BEFORE NONCARDIAC SURGERY REDUCE THE RISK OF CORONARY EVENTS IN PATIENTS WITH KNOWN CORONARY-ARTERY DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID MAJOR VASCULAR-SURGERY; NON-CARDIAC SURGERY C1 CLEVELAND CLIN,DIV CARDIOL,CLEVELAND,OH 44106. UNIV MICHIGAN,MED CTR,DIV CARDIOL,ANN ARBOR,MI 48109. RP DOMANSKI, M (reprint author), NHLBI,CLIN TRIALS GRP,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 14 Z9 14 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1995 VL 75 IS 12 BP 829 EP 831 DI 10.1016/S0002-9149(99)80422-6 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QT062 UT WOS:A1995QT06200017 PM 7717290 ER PT J AU COTCH, MF FAUCI, AS HOFFMAN, GS AF COTCH, MF FAUCI, AS HOFFMAN, GS TI HLA TYPING IN PATIENTS WITH WEGENER GRANULOMATOSIS SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RP COTCH, MF (reprint author), RES TRIANGLE INST,CTR MED ENVIRONM & ENERGY,ROCKVILLE,MD 20852, USA. FU Intramural NIH HHS [Z99 EY999999] NR 4 TC 15 Z9 15 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1995 VL 122 IS 8 BP 635 EP 635 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QR525 UT WOS:A1995QR52500029 PM 7887571 ER PT J AU BACHERE, E MIALHE, E NOEL, D BOULO, V MORVAN, A RODRIGUEZ, J AF BACHERE, E MIALHE, E NOEL, D BOULO, V MORVAN, A RODRIGUEZ, J TI KNOWLEDGE AND RESEARCH PROSPECTS IN MARINE MOLLUSK AND CRUSTACEAN IMMUNOLOGY SO AQUACULTURE LA English DT Article; Proceedings Paper CT 5th International Colloquium on Pathology in Marine Aquaculture (PAMAQ V) CY APR 02-04, 1992 CL MONTPELLIER, FRANCE DE IMMUNOLOGY; MOLLUSKS; CRUSTACEANS ID OYSTER CRASSOSTREA-VIRGINICA; HORSESHOE-CRAB HEMOCYTES; DIPTERAN PHORMIA-TERRANOVAE; BONAMIA-OSTREAE PROTOZOA; MUSSEL MYTILUS-EDULIS; IN-VITRO CULTURE; INSECT IMMUNITY; PERKINSUS-MARINUS; ANTIBACTERIAL PEPTIDES; ANTIMICROBIAL PEPTIDES AB In the context of infectious diseases in mollusc and shrimp aquaculture, research must be focused on diagnosis for zoosanitary controls but also on obtaining resistant animals. This last strategy depends heavily on the development of knowledge about marine invertebrate immunology. With the establishment of purification protocols for the main invertebrate pathogens, progress has been made in the study of host-pathogen interactions at cellular and molecular levels and in identifying immune effecters involved in the destruction of pathogens. Recent information on molluscs and crustaceans is presented, concerning both hemocyte studies and cellular defence functions and humoral effecters, with special reference to their application to selection of pathogen-resistant animals. With this aim, research prospects will essentially be devoted to the identification and characterization of immune genes, either specific or heterologous, which could be candidates for mollusc and shrimp genetic transformation. C1 NIAID, MALARIA RES LAB, BETHESDA, MD 20892 USA. ESPOL, CENAIM, GUAYAQUIL, ECUADOR. RP BACHERE, E (reprint author), UNIV MONTPELLIER 2, IFREMER,CNRS,UMR 9947,UM2,CP80, PL E BATAILLON, F-34095 MONTPELLIER, FRANCE. RI Noel, Daniele/E-5719-2016 NR 107 TC 109 Z9 126 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD APR 15 PY 1995 VL 132 IS 1-2 BP 17 EP 32 DI 10.1016/0044-8486(94)00389-6 PG 16 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA QV981 UT WOS:A1995QV98100002 ER PT J AU MIALHE, E BACHERE, E BOULO, V CADORET, JP AF MIALHE, E BACHERE, E BOULO, V CADORET, JP TI STRATEGY FOR RESEARCH AND INTERNATIONAL-COOPERATION IN MARINE INVERTEBRATE PATHOLOGY, IMMUNOLOGY AND GENETICS SO AQUACULTURE LA English DT Article; Proceedings Paper CT 5th International Colloquium on Pathology in Marine Aquaculture (PAMAQ V) CY APR 02-04, 1992 CL MONTPELLIER, FRANCE DE PATHOLOGY; IMMUNOLOGY; GENETICS; INVERTEBRATES ID HEMATOPOIETIC NECROSIS VIRUS; TRANSGENIC MICE; PENAEID SHRIMP; AEDES-AEGYPTI; DNA; PURIFICATION; EXPRESSION; TRANSFORMATION; RESISTANCE; MOSQUITO AB During the last 10 years, marine invertebrate pathology has moved from morphological description and microscopic diagnosis of pathogens to molecular characterization of these pathogens and probe-based diagnostics, Studies of host-pathogen interactions were undertaken to understand the immunity of molluscs and shrimps with a special new emphasis on immune gene characterization. Recently, genetic transformation has been considered for selecting resistant strains because of the numerous successes obtained with transgenic plants and vertebrates. The production of transgenic molluscs and shrimps, with genes or antisense sequences conferring resistance to specific pathogens, certainly constitutes a new priority for aquaculture. The quick development of research from pathology to immunology and genetics has been made possible partially by developing international cooperation to compensate for the limited manpower, on one hand inside the network of the pathologists, and on the other hand by removing barriers between topics. Regular meetings appear useful for regularly managing research in pathology-immunology-genetics of molluscs and shrimps, for analysing the strategy according to advances in similar fields related to other animal or plant groups, and for improving international cooperation between all scientists concerned from developing and developed countries. C1 UNIV MONTPELLIER 2,IFREMER,CNRS,F-34095 MONTPELLIER 05,FRANCE. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NR 53 TC 19 Z9 19 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD APR 15 PY 1995 VL 132 IS 1-2 BP 33 EP 41 DI 10.1016/0044-8486(94)00383-Y PG 9 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA QV981 UT WOS:A1995QV98100003 ER PT J AU TSUJI, K COPELAND, NG JENKINS, NA OBINATA, M AF TSUJI, K COPELAND, NG JENKINS, NA OBINATA, M TI MAMMALIAN ANTIOXIDANT PROTEIN COMPLEMENTS ALKYLHYDROPEROXIDE REDUCTASE (AHPC) MUTATION IN ESCHERICHIA-COLI SO BIOCHEMICAL JOURNAL LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; MURINE ERYTHROLEUKEMIA-CELLS; SALMONELLA-TYPHIMURIUM; GENE; CLONING; MOUSE; HOMOLOGY; IDENTIFICATION; CHROMOSOMES; SEQUENCE AB The MER5 [now called the Aop1 (antioxidant protein 1) gene] was cloned as a transiently expressed gene of murine erythro leukaemia (MEL) cell differentiation and its antisense expression inhibited differentiation of MEL cells. We found that the Aop1 gene shows significant nucleotide sequence similarity to the gene for the C22 subunit of Salmonella typhimurium alkyl hydroperoxide reductase, which is also found in other bacteria, suggesting it functions as an antioxidant protein. Expression of the Aop1 gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide. The human and mouse Aop1 genes are highly conserved, and they mapped to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian Aop1 homologues suggest that these genes consist of a family that is responsible for regulation of cellular proliferation, differentiation and antioxidant functions. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP TSUJI, K (reprint author), TOHOKU UNIV,INST DEV AGING & CANC,DEPT CELL BIOL,AOBA KU,SENDAI,MIYAGI 980,JAPAN. FU NCI NIH HHS [N01-CO-74101] NR 19 TC 55 Z9 57 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1995 VL 307 BP 377 EP 381 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RA063 UT WOS:A1995RA06300010 PM 7733872 ER PT J AU SMITH, JB YANG, ZJ LIN, PP ZAIDI, Z ABBASI, A RUSSELL, P AF SMITH, JB YANG, ZJ LIN, PP ZAIDI, Z ABBASI, A RUSSELL, P TI THE COMPLETE SEQUENCE OF HUMAN LENS GAMMA-S-CRYSTALLIN SO BIOCHEMICAL JOURNAL LA English DT Article AB The complete sequence of human gamma s-crystallin has been determined and confirmed using a combination of MS methods, peptide sequencing and cDNA sequencing. Regions 21-35 and 102-107, which were previously assumed to be the same as the bovine sequence, differ from the bovine sequence at residues 22, 28, 31 and 104. An additional six residues were also found to be different from the original sequence determined for Pakastani lenses. Whether these differences represent errors in the original sequence or two different sequences among human lens crystallins is not yet known. C1 UNIV KARACHI,HEJ RES INST CHEM,KARACHI 75270,PAKISTAN. NEI,BETHESDA,MD 20892. RP SMITH, JB (reprint author), PURDUE UNIV,DEPT MED CHEM,W LAFAYETTE,IN 47907, USA. RI Abbasi, Atiya/G-1242-2010 FU NEI NIH HHS [EY07609] NR 6 TC 15 Z9 16 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1995 VL 307 BP 407 EP 410 PN 2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RA063 UT WOS:A1995RA06300014 PM 7733876 ER PT J AU DEMITRACK, MA HEYES, MP ALTEMUS, M PIGOTT, TA GOLD, PW AF DEMITRACK, MA HEYES, MP ALTEMUS, M PIGOTT, TA GOLD, PW TI CEREBROSPINAL-FLUID LEVELS OF KYNURENINE PATHWAY METABOLITES IN PATIENTS WITH EATING DISORDERS - RELATION TO CLINICAL AND BIOCHEMICAL VARIABLE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE L-TRYPTOPHAN; QUINOLINIC ACID; KYNURENIC ACID; EATING DISORDERS ID CENTRAL NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; QUINOLINIC ACID; RAT-BRAIN; NEUROLOGICAL DISEASE; ANOREXIA-NERVOSA; NMDA; INDOLEAMINE-2,3-DIOXYGENASE; QUANTIFICATION; CHROMATOGRAPHY AB In brain, most L-tryptophan is metabolized to indoleamines, whereas in systemic tissues L-tryptophan is catabolized to kynurenine pathway metabolites. Among these latter compounds are: quinolinic acid, an N-methyl-D-aspartate receptor agonist; kynurenic acid, an antagonist of excitatory amino acid receptors that also reduces quinolinic acid-mediated neurotoxicity; and L-kynurenine, a possible convulsant, Because the metabolism of L-tryptophan through the kynurenine pathway is dependent upon adequate nutrition, we sought to determine whether the impaired nutrition characteristic of eating-disordered patients might be associated with specific disturbances in this metabolic pathway, Cerebrospinal fluid levels of L-tryptophan, quinolinic acid kynurenic acid, L-kynurenine, and 5-hydroxyindoleacetic acid were measured in medication-free female patients meeting DSM-III-R criteria for either anorexia nervosa (n = 10) or normal weight bulimia nervosa (n = 22), studied at varying stages of nutritional recovery, Eight healthy, normal-weight females served as a comparison group., Cerebrospinal fluid levels of kynurenic acid were significantly reduced in underweight anorectics, compared to normal females, but returned to normal values with restoration of normal body weight, Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa. Furthermore, in the eating-disordered patients, kynurenic acid levels in cerebrospinal fluid correlated positively with percent-of-population average body weight, Cerebrospinal fluid 5-hydroxyindoleacetic acid levels were reduced in underweight patients with anorexia nervosa, These results indicate that perturbations in kynurenine metabolism occur in patients with anorexia nervosa, possibly as a consequence of the nutritional compromise associated with the underweight phase of the illness C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP DEMITRACK, MA (reprint author), UNIV MICHIGAN,MED CTR,DEPT PSYCHIAT,MICHIGAN EATING DISORDERS PROGRAM,1500 E MED CTR DR,ANN ARBOR,MI 48109, USA. RI Demitrack, Mark/I-7697-2013 NR 37 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD APR 15 PY 1995 VL 37 IS 8 BP 512 EP 520 DI 10.1016/0006-3223(94)00173-Z PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QU283 UT WOS:A1995QU28300004 PM 7542489 ER PT J AU FOLI, BA SAVILLE, MW BASELER, MW YARCHOAN, R AF FOLI, BA SAVILLE, MW BASELER, MW YARCHOAN, R TI EFFECTS OF THE TH-1 AND TH-2 STIMULATORY CYTOKINES INTERLEUKIN-12 AND INTERLEUKIN-4 ON HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION SO BLOOD LA English DT Article ID BLOOD MONONUCLEAR-CELLS; RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; IMMUNE-RESPONSES; IFN-GAMMA; MURINE LEISHMANIASIS; INTERFERON-GAMMA; TH2 CELLS; INFECTION; IL-4 AB The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the development of Th-1-like (type-1) and Th-2-like (type-2) T-cell responses, respectively, and there is evidence that type-1/type-2 T helper imbalances are important in the pathogenesis of human immunodeficiency virus (HIV) disease. With this background, we examined the effects of these cytokines on HIV replication. Neither stimulated HIV replication in fresh peripheral blood mononuclear cells (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300 x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000 x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4(+) subset in stimulated cultures. IL-4 stimulated HIV replication in monocyte/macrophages. while IL-12 had little or no effect in these cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced cell death in prestimulated PBMC. Through killing of the CD4(+) T cells stimulated by these cytokines, this may result in inappropriate type-1/type-2 responses in HIV-infected patients and contribute to their Th-1 immunodeficiency. This is a US government work. There are no restrictions on its use. C1 NIH,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 70 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1995 VL 85 IS 8 BP 2114 EP 2123 PG 10 WC Hematology SC Hematology GA QU092 UT WOS:A1995QU09200017 ER PT J AU ZAHM, SH BLAIR, A CANTOR, KP FRAUMENI, JF AF ZAHM, SH BLAIR, A CANTOR, KP FRAUMENI, JF TI OTHER AMERICAN-STUDIES FAIL TO CONFIRM AN ASSOCIATION SO BRITISH MEDICAL JOURNAL LA English DT Letter ID NON-HODGKINS-LYMPHOMA; RISK C1 NCI,EPIDEMIOL & BIOSTAT PROGRAMME,ENVIRONM STUDIES SECT,ROCKVILLE,MD 20892. RP ZAHM, SH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAMME,OCCUPAT STUDIES SECT,EPN 418,ROCKVILLE,MD 20892, USA. NR 7 TC 10 Z9 10 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 APR 15 PY 1995 VL 310 IS 6985 BP 1009 EP 1010 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QT904 UT WOS:A1995QT90400070 PM 7728011 ER PT J AU FIGG, WD THIBAULT, A COOPER, MR REID, R HEADLEE, D DAWSON, N KOHLER, DR REED, E SARTOR, O AF FIGG, WD THIBAULT, A COOPER, MR REID, R HEADLEE, D DAWSON, N KOHLER, DR REED, E SARTOR, O TI A PHASE-I STUDY OF THE SOMATOSTATIN ANALOG SOMATULINE IN PATIENTS WITH METASTATIC HORMONE-REFRACTORY PROSTATE-CANCER SO CANCER LA English DT Article DE PROSTATE CANCER; SOMATULINE; SOMATOSTATIN; PHASE I; IGF-I; HORMONE-REFRACTORY; INSULIN-LIKE GROWTH FACTOR ID GROWTH-FACTOR; IGF-I; PROLACTIN; RADIOIMMUNOASSAY; SMS-201-995; SANDOSTATIN; OCTREOTIDE; RECEPTORS; NEOPLASMS; THERAPY AB Background. Somatuline, a somatostatin analogue, has proven to be effective in several animal models of prostate cancer. Preliminary clinical studies also have suggested antitumor activity in patients with prostate cancer. The authors conducted a dose-escalation trial of 25 patients with metastatic hormone-refractory prostate cancer. Methods. Dosages of 4, 7, 10, 13, 18, and 24 mg/day were administered by continuous intravenous infusion for at least 28 days. Results. Plasma levels of insulin-like growth factor-I (IGF-I), but not those of IGF-II, declined modestly during therapy. Toxicities included grade I diarrhea, bloating, infection, nausea, and flatus. The gastrointestinal side effects were typically self-limiting and occurred during the initial portion of treatment cycles. In addition, three patients experienced grade II catheter-related infections. No clinical response was noted by either radiographic or tumor marker criteria. The maximally tolerated dose of somatuline was not determined. Conclusion. A continuous intravenous infusion of 24 mg/day of somatuline is well tolerated and could be evaluated in other types of cancer or possibly in less advanced prostate cancer, but no clinical activity was noted at this dose in patients with advanced metastatic hormone-refractory prostate cancer. C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD. RP FIGG, WD (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A01,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 36 TC 40 Z9 40 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 APR 15 PY 1995 VL 75 IS 8 BP 2159 EP 2164 DI 10.1002/1097-0142(19950415)75:8<2159::AID-CNCR2820750820>3.0.CO;2-O PG 6 WC Oncology SC Oncology GA QR317 UT WOS:A1995QR31700019 PM 7535186 ER PT J AU TAKAHASHI, H FURUSATO, M ALLSBROOK, WC NISHII, H WAKUI, S BARRETT, JC BOYD, J AF TAKAHASHI, H FURUSATO, M ALLSBROOK, WC NISHII, H WAKUI, S BARRETT, JC BOYD, J TI PREVALENCE OF ANDROGEN RECEPTOR GENE-MUTATIONS IN LATENT PROSTATIC CARCINOMAS FROM JAPANESE MEN SO CANCER RESEARCH LA English DT Note ID CANCER; INSENSITIVITY AB The incidence rate of clinically apparent prostatic carcinoma is 8-fold higher in the United States than in Japan, while the prevalence of latent prostatic carcinoma, a presumed precursor to clinical carcinoma, is similar in the two countries. The purpose of this study was to investigate the hypothesis that this profound difference in incidence rates of clinical carcinoma reflects distinct profiles of molecular genetic alterations in the latent precursor lesions that occur in the two countries. A significant fraction of latent carcinomas from Japanese men were found to contain inactivating mutations of the androgen receptor gene, white no such mutations were found in latent carcinomas from American men. No mutations were found in clinical carcinomas from either country. These data offer a potential molecular genetic explanation that may partially account for the distinct prostatic carcinoma incidence rates in these two populations. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. JIKEI UNIV,SCH MED,DEPT PATHOL,TOKYO 105,JAPAN. MED COLL GEORGIA,DEPT PATHOL,AUGUSTA,GA 30912. NR 24 TC 69 Z9 72 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 APR 15 PY 1995 VL 55 IS 8 BP 1621 EP 1624 PG 4 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300005 PM 7712463 ER PT J AU FAN, SJ SMITH, ML RIVET, DJ DUBA, D ZHAN, QM KOHN, KW FORNACE, AJ OCONNOR, PM AF FAN, SJ SMITH, ML RIVET, DJ DUBA, D ZHAN, QM KOHN, KW FORNACE, AJ OCONNOR, PM TI DISRUPTION OF P53 FUNCTION SENSITIZES BREAST-CANCER MCF-7 CELLS TO CISPLATIN AND PENTOXIFYLLINE SO CANCER RESEARCH LA English DT Note ID TUMOR-SUPPRESSOR GENE; DNA-DAMAGE; CYCLE; LINES; CHECKPOINTS; MUTATIONS; AGENTS AB The possibility that appropriately designed chemotherapy could act selectively against p53-defective tumor cells was explored in MCF-7 human breast cancer cells. These cells were chosen because they have normal p53 function but are representative of a tumor cell type that does not readily undergo p53-dependent apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53 function was disrupted by transfection with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and MCF-7/mu-p53 cells was defective relative to control cells in that there were no increases in p53 or p21(Waf1/Cip1) protein levels and no G(1) arrest following exposure to ionizing radiation. Survival assays showed that p53 disruption sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired extensively by nucleotide excision, and in agreement with a defect in this process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells with disrupted p53 to defects in G(1) checkpoint control, nucleotide excision repair, or both. The G(2) checkpoint inhibitor pentoxifylline exhibited synergism with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control cells. Moreover, pentoxifylline inhibited G(2) checkpoint function to a greater extent in MCF-7/E6 than in the parental cells. These results suggested that, in the absence of p53 function, cancer cells are more vulnerable to G(2) checkpoint abrogators. Our results show that a combination of CDDP and pentoxifylline is capable of synergistic and preferential killing of p53-defective tumor cells that do not readily undergo apoptosis. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 43 TC 544 Z9 555 U1 0 U2 10 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 APR 15 PY 1995 VL 55 IS 8 BP 1649 EP 1654 PG 6 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300011 PM 7712469 ER PT J AU CLIFFORD, A MORGAN, D YUSPA, SH SOLER, AP GILMOUR, S AF CLIFFORD, A MORGAN, D YUSPA, SH SOLER, AP GILMOUR, S TI ROLE OF ORNITHINE DECARBOXYLASE IN EPIDERMAL TUMORIGENESIS SO CANCER RESEARCH LA English DT Article ID ACID RETINOIC ACID; MOUSE SKIN; ALPHA-DIFLUOROMETHYLORNITHINE; CELL-TRANSFORMATION; MESSENGER-RNA; POLYAMINE BIOSYNTHESIS; IRREVERSIBLE INHIBITOR; 5'-UNTRANSLATED REGION; GENE-EXPRESSION; TUMOR PROMOTION AB Ornithine decarboxylase (ODC) plays a key role in the biosynthesis of polyamines, which are necessary for cell growth and differentiation. ODC expression is very tightly controlled in all normal cells; however, regulation of its expression is altered in many tumor cells resulting in much higher basal levels of ODC in tumors. To investigate the potential role of ODC overexpression in epidermal tumorigenesis, we constructed a replication-defective retroviral vector to overexpress a truncated ODC protein in epidermal cells. Stable viral infection of mouse epidermal cells dramatically increases not only the basal ODC activity but also the basal putrescine and spermidine levels. In all infected epidermal cells with high polyamine levels, DNA synthesis is increased as measured by [H-3]thymidine incorporation into DNA as well as increased bromodeoxyuridine staining in the nuclei of ODC-infected epidermal cells. ODC viral infection of nontumorigenic BK-1 epidermal cells and primary cultures of mouse keratinocytes and fibroblasts from newborn mouse skin yields no tumors when injected s.c. into athymic nude mice or when transplanted as skin grafts onto nude mice. Epidermal cell lines SP-1 and 308 (which possess an activated ras(Ha) gene) are not tumorigenic when injected s.c. into nude mice. However, following infection with the ODC virus, they form tumors filled with keratin and papilloma-like projections of hyperplastic epidermal cells displaying dysplasia and many mitotic figures. These data indicate that ODC overexpression by itself is not sufficient to induce tumors in normal cells but that increased expression of ODC enhances tumor development in initiated premalignant epidermal cells. C1 LANKENAU MED RES CTR,WYNNEWOOD,PA 19096. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA55066] NR 56 TC 119 Z9 122 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 APR 15 PY 1995 VL 55 IS 8 BP 1680 EP 1686 PG 7 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300017 PM 7712475 ER PT J AU MCCABE, BJ IRVINE, KR NISHIMURA, MI YANG, JC SPIESS, PJ SHULMAN, EP ROSENBERG, SA RESTIFO, NP AF MCCABE, BJ IRVINE, KR NISHIMURA, MI YANG, JC SPIESS, PJ SHULMAN, EP ROSENBERG, SA RESTIFO, NP TI MINIMAL DETERMINANT EXPRESSED BY A RECOMBINANT VACCINIA VIRUS ELICITS THERAPEUTIC ANTITUMOR CYTOLYTIC T-LYMPHOCYTE RESPONSES SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; SYNTHETIC LIPOPEPTIDE VACCINE; AUTOLOGOUS TUMOR; ENDOGENOUS ANTIGENS; IMMUNE-RESPONSES; NECROSIS-FACTOR; HUMAN-MELANOMA; CELL EPITOPE; INVIVO; IDENTIFICATION AB Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by CD8+ T lymphocytes (T-CD8+). To explore the possibility of using a genetically encoded, minimally sized fragment of an intracellular antigen as an immunogen, we constructed a recombinant vaccinia virus encoding an 8-residue peptide derived from chicken ovalbumin that is known to associate with the mouse H-2K(b) molecule. Compared to standard methods of immunization, recombinant vaccinia virus expressing the minimal determinant as well as full length ovalbumin were the only approaches that elicited specific primary lytic responses in C57BL/6 mice against E.G7OVA, a transfectant of the murine thymoma EL4 containing the ovalbumin gene. Stimulating these effecters in vitro with OVA(257-264) peptide induced H-2K(b)-restricted T-CD8+ that not only lysed but also specifically secreted IFN-gamma in response to an antigen. Furthermore, when transferred adoptively, these anti-OVA(257-264) T-CD8+ cells significantly reduced the growth of established ovalbumin-transfected tumors in a pulmonary metastasis model system. Synthetic oligonucleotides encoding minimal antigenic determinants within expression constructs may be a useful approach for treatment of neoplastic disease, thus avoiding the potential hazards of immunizing with full-length cDNAs that are potentially oncogenic. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 55 TC 41 Z9 41 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 APR 15 PY 1995 VL 55 IS 8 BP 1741 EP 1747 PG 7 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300026 PM 7536130 ER PT J AU PAULES, RS LEVEDAKOU, EN WILSON, SJ INNES, CL RHODES, N TLSTY, TD GALLOWAY, DA DONEHOWER, LA TAINSKY, MA KAUFMANN, WK AF PAULES, RS LEVEDAKOU, EN WILSON, SJ INNES, CL RHODES, N TLSTY, TD GALLOWAY, DA DONEHOWER, LA TAINSKY, MA KAUFMANN, WK TI DEFECTIVE G(2) CHECKPOINT FUNCTION IN CELLS FROM INDIVIDUALS WITH FAMILIAL CANCER SYNDROMES SO CANCER RESEARCH LA English DT Article ID CHINESE-HAMSTER OVARY; WILD-TYPE P53; ATAXIA TELANGIECTASIA LYMPHOCYTES; P34CDC2 PROTEIN-KINASE; IONIZING-RADIATION; FISSION YEAST; CYCLIN-B; DNA DAMAGE; HELA-CELLS; SACCHAROMYCES-CEREVISIAE AB The early events in the G(2) checkpoint response to ionizing radiation (IR) were analyzed in diploid normal human fibroblasts (NHFs) and fibroblasts from patients with two heritable cancer syndromes. Exposure to gamma-radiation of asynchronously growing NHFs resulted in a rapid reduction in the number of cells in mitosis (G(2) delay) and was accompanied by a quantitatively similar reduction in the p34(CDC2)/cyclin B in vitro histone H1 kinase activity as compared with sham-treated controls. This G(2) delay was strong by 1 h following exposure to IR, maximal by 2 h, and was accompanied by an accumulation of tyrosine-phosphorylated p34(CDC2) molecules. In contrast, fibroblasts from individuals with ataxia telangiectasia displayed significantly less reduction of the mitotic index or histone H1 kinase activity after IR. Low passage fibroblasts from individuals with Li-Fraumeni syndrome having one wild-type and one mutated p53 allele were similar to NHFs in their immediate G(2) checkpoint response to IR, as were NHFs expressing the human papilloma virus type 16 E6 gene product (functionally inactivating p53) and low passage cells from p53-deficient mouse embryos. However, the p53-deficient fibroblasts were genomically unstable and became defective in their early G(2) checkpoint response to IR. Furthermore, immortal Li-Fraumeni syndrome fibroblasts lacking wild-type p53 displayed an attenuated G(2) checkpoint response. These results link the early events in G(2) checkpoint response to IR in NHFs with a rapid inhibition of p34(CDC2)/cyclin B protein kinase activity and demonstrate that while not required for this immediate G(2) delay, lack of p53 can lead to subsequent genetic alterations that result in defective G(2) checkpoint function. C1 UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. RP PAULES, RS (reprint author), NIEHS,GROWTH CONTROL & CANC GRP,MAIL DROP C1-09,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA42765, P01 CA042765] NR 85 TC 165 Z9 166 U1 2 U2 5 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 APR 15 PY 1995 VL 55 IS 8 BP 1763 EP 1773 PG 11 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300030 PM 7712486 ER PT J AU MATSUMOTO, K WADA, RK YAMASHIRO, JM KAPLAN, DR THIELE, CJ AF MATSUMOTO, K WADA, RK YAMASHIRO, JM KAPLAN, DR THIELE, CJ TI EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND P145(TRKB) AFFECTS SURVIVAL, DIFFERENTIATION, AND INVASIVENESS OF HUMAN NEUROBLASTOMA-CELLS SO CANCER RESEARCH LA English DT Article ID NERVE GROWTH-FACTOR; HUMAN NEURO-BLASTOMA; TRK PROTOONCOGENE PRODUCT; FACTOR RECEPTOR; PROTEIN-KINASE; TYROSINE KINASE; N-MYC; INHIBITION; GENE; NGF AB A large number of poor prognosis neuroblastoma (NB) tumors constitutively express brain-derived neurotrophic factor (BDNF) and variably express the gene for its tyrosine kinase (Trk) receptor TrkB. Good prognosis NB tumors typically express high levels of TrkA mRNA, which encodes the signal transducing receptor for nerve growth factor, p140(TrkA). These neurotrophins are necessary for neural cell survival and differentiation. This study evaluates the effects of activation of the BDNF-TrkB signal transduction pathway on the growth, survival, morphology, and invasive capacity of NB cells. We find that the addition of BDNF to SY5Y cells induced to express p145(TrkB) by retinoic acid treatment does not significantly affect cell proliferation yet will support cell survival. Activation of the BDNF-TrkB signal transduction pathway stimulates disaggregation of cells and extension of neuritic processes which can be blocked by a BDNF-neutralizing antibody. Treatment of cells with K252a, an inhibitor of Trk, reverses the cellular disaggregation. An evaluation of the effects of BDNF and nerve growth factor on the ability of NB cells to penetrate basement membrane proteins indicated that BDNF stimulated a 2-fold increase while nerve growth factor inhibited RA-SY5Y cell invasion. Thus, activation of the p145(TrkB) signal transduction pathway stimulates NB cell survival, disaggregation, and invasion; all characteristics of metastatic cells. Furthermore, these studies indicate that activation of different Trk signal transduction pathways in NB cells results in distinct differences in tumor cell biology and these may be relevant to the clinical course of the patients. C1 NCI,PEDIAT BRANCH,CELL & MOLEC BIOL SECT,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. GWYNNE HAZEN CHERRY MEM LABS,LOS ANGELES,CA 90024. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 46 TC 157 Z9 164 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1995 VL 55 IS 8 BP 1798 EP 1806 PG 9 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300035 PM 7712490 ER PT J AU GOULD, AL ROSSOUW, JE SANTANELLO, NC HEYSE, JF FURBERG, CD AF GOULD, AL ROSSOUW, JE SANTANELLO, NC HEYSE, JF FURBERG, CD TI CHOLESTEROL REDUCTION YIELDS CLINICAL BENEFIT - A NEW LOOK AT OLD DATA SO CIRCULATION LA English DT Article DE CHOLESTEROL; METAANALYSIS; MORTALITY ID CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; MIDDLE-AGED MEN; SECONDARY PREVENTION; LOWERING CHOLESTEROL; ARTERY DISEASE; MORTALITY; THERAPY; RISK; METAANALYSIS AB Background There has been a continuing debate about the overall benefit of cholesterol lowering. We performed a novel meta-analysis of all randomized trials of more than 2 years' duration (n=35 trials) to describe how coronary-heart-disease (CHD), non-CHD, and total mortality are related to cholesterol lowering and to type of intervention. Methods and Results The analytic approach was designed to separate the effects of cholesterol lowering itself from the other effects of the different types of intervention used. For every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% (P<.002) and total mortality by 10% (P<.03). Cholesterol lowering had no effect on non-CHD mortality. Certain types of intervention had specific effects independent of cholesterol lowering. Fibrates (clofibrates, 7 trials; gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P<.01) and total mortality by about 17% (P<.02). Hormones (estrogen, 2 trials; dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P<.04), non-CHD mortality by about 55% (P<.03), and total mortality by about 33% (P<.01). No specific effects independent of cholesterol lowering were found due to diet (n=11) or other interventions (resins, 5; niacin, 3; statins, 2; partial ileal bypass, 1). Conclusions The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality. C1 NIH,BETHESDA,MD. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. RP GOULD, AL (reprint author), MERCK & CO INC,RES LABS,BL3-2,W POINT,PA 19486, USA. NR 72 TC 204 Z9 209 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 1995 VL 91 IS 8 BP 2274 EP 2282 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QR285 UT WOS:A1995QR28500023 PM 7697857 ER PT J AU MERTA, A AKSAMIT, RR KASIR, J CANTONI, GL AF MERTA, A AKSAMIT, RR KASIR, J CANTONI, GL TI THE GENE AND PSEUDOGENES OF RAT S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE; GENE; PSEUDOGENES; SEQUENCE; INTERMEDIATE DISPERSED SEQUENCES ID AMINO-ACID SEQUENCE; ADENOSYLHOMOCYSTEINE HYDROLASE; DICTYOSTELIUM-DISCOIDEUM; CDNA SEQUENCE; DNA-SEQUENCE; CPG ISLANDS; PURIFICATION; MOUSE; LIVER; CELLS AB Two rat liver genomic DNA libraries constructed in lambda DASH and lambda Charon 4A were screened for sequences with similarity to S-adenosyl-L-homocysteine (AdoHcy) hydrolase cDNA. Of 36 clones purified, two contained the AdoHcy hydrolase gene sequence and 34 contained pseudogene sequences. The AdoHcy hydrolase gene, which has been sequenced in its entirety, spans approximately 15 kb and consists of 10 exons. Primer extension and S1 experiments show that transcription is initiated from two major initiation sites located at positions -63 and -62 from the starting codon and from several minor sites. The promoter region is located in a CpG island, sequence TATTTAAA is present 23 bases upstream from the transcription start site, and an inverted CCAAT box is located 285 bp upstream from the transcription start site. Other potential transcription-factor binding sites including SP1, AP-2, GRE and Oct-1 sites were identified in the 5'-flanking region. Several different processed pseudogenes were found and analyzed. C1 NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. NR 42 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD APR 15 PY 1995 VL 229 IS 2 BP 575 EP 582 DI 10.1111/j.1432-1033.1995.tb20500.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT651 UT WOS:A1995QT65100029 PM 7744082 ER PT J AU LOUIE, S CAI, J LAW, R LIN, G LUNARDIISKANDAR, Y JUNG, B MASOOD, R GILL, P AF LOUIE, S CAI, J LAW, R LIN, G LUNARDIISKANDAR, Y JUNG, B MASOOD, R GILL, P TI EFFECTS OF INTERLEUKIN-1 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST IN AIDS-KAPOSIS SARCOMA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE KAPOSIS SARCOMA; INTERLEUKIN-1; INTERLEUKIN-1 RECEPTOR ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; CELLS; CULTURE; EXPRESSION; CYTOKINES; MONOCYTES; INHIBITOR; ALPHA AB Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV-1 infection. HIV-1 may induce KS directly through viral protein(s) or indirectly through regulation of cytokines such as IL-1 and IL-6. We have shown that AIDS-KS spindle cells express IL-1 beta and that IL-1ra inhibits KS-spindle cell growth. IL-1ra had little effect on human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASM), and human foreskin fibroblast (NN41). These findings support an autocrine activity for IL-1. Furthermore, exogenous IL-1 can enhance AIDS-KS cell growth, and this effect is completely blocked by IL-1ra. As expected, IL-1ra also blocks IL-1 mediated upregulation of IL-6 and bFGF, both of which are autocrine growth factors for KS, IL-1ra is thus a potential candidate for the treatment of AIDS-associated KS. C1 UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH PHARM,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA51621-03]; NHLBI NIH HHS [HL48499-02] NR 18 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 15 PY 1995 VL 8 IS 5 BP 455 EP 460 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QR080 UT WOS:A1995QR08000004 PM 7697441 ER PT J AU MUNOZ, A KIRBY, AJ HE, YD MARGOLICK, JB VISSCHER, BR RINALDO, CR KASLOW, RA PHAIR, JP AF MUNOZ, A KIRBY, AJ HE, YD MARGOLICK, JB VISSCHER, BR RINALDO, CR KASLOW, RA PHAIR, JP TI LONG-TERM SURVIVORS WITH HIV-1 INFECTION - INCUBATION PERIOD AND LONGITUDINAL PATTERNS OF CD4(+) LYMPHOCYTES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE STUDY DESIGN; INCUBATION PERIOD; CD4(+) LYMPHOCYTES; STATISTICAL MODELS ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; HOMOSEXUAL MEN; T SUBSETS; PREDICTORS; TYPE-1 AB To characterize long-term survival with HIV-1, we need to estimate the proportion of seroconverters remaining free from clinical AIDS for long periods. We predict that similar to 13% of homosexual/bisexual men infected at a young age may remain so for >20 years. Since studies have not followed individuals for such periods, long-term survivors must be characterized using stability of immunologic markers. In a cohort of 1,809 seropositive men followed since 1984-85, 15% (187/1,214) of those with at least two consecutive visits early in the study showed no decline in CD4(+) cell count. From these, 67 men with long follow-up and no use of zidovudine were identified as cases to investigate correlates of protection against HIV-l-induced immunodepletion. Two matched control subgroups, one with moderate and one with rapid CD4(+) lymphocyte decline, produced 56 triplets of individuals to be contrasted. Analysis of data from early in the study on demographics, sexual behavior, and sexually transmitted diseases revealed no significant differences among the three groups. Men showing no decline in CD4(+) lymphocytes persistently showed a healthier profile with respect to onset of clinical AIDS, survival, and concomitant hematologic variables. Moderate decliners had rates of clinical AIDS and death significantly higher than those in the stable group but lower than the fast decliners. C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. NIAID,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP MUNOZ, A (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,HAMPTON HOUSE,RM 797,624 N BROADWAY,BALTIMORE,MD 21205, USA. FU PHS HHS [U01-A1-35041, U01-A1-35042, U01-A1-35039] NR 29 TC 95 Z9 99 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 15 PY 1995 VL 8 IS 5 BP 496 EP 505 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QR080 UT WOS:A1995QR08000010 PM 7697447 ER PT J AU BACON, KB FLORESROMO, L LIFE, PF TAUB, DD PREMACK, BA ARKINSTALL, SJ WELLS, TNC SCHALL, TJ POWER, CA AF BACON, KB FLORESROMO, L LIFE, PF TAUB, DD PREMACK, BA ARKINSTALL, SJ WELLS, TNC SCHALL, TJ POWER, CA TI IL-8-INDUCED SIGNAL-TRANSDUCTION IN T-LYMPHOCYTES INVOLVES RECEPTOR-MEDIATED ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; HUMAN INTERLEUKIN-8 RECEPTOR; CHEMOTACTIC ACTIVITY; MONOCLONAL-ANTIBODY; CELLS; MIGRATION; MIP-1-ALPHA; INHIBITION; EXPRESSION; HYDROLYSIS AB We have characterized the IL-8-induced signal transduction processes in T lymphocytes. A basal level of IL-8 receptor expression was shown on mixed PBL, as identified by using phycoerythrin (PE)-coupled IL-8, and this expression was increased following IL-2 stimulation. Scatchard analysis of T cells revealed competitive binding of IL-8 with a K-d of 0.55 nM, with approximately 1200 receptors per cell, on freshly isolated T cells. After 24 h in culture following purification, reverse transcriptase PCR (RT-PCR) analyses show the mRNA for only the type B IL-8R on these cultured T lymphocytes and the cell line MOLT-4. Stimulation of T lymphocytes or T cell clones with IL-8 led to generation of inositol trisphosphate and calcium flux. In addition, when T cells were prelabeled with [H-3]oleic acid, IL-8 caused a long lasting, time- and dose-related increase in [H-3] phosphatidylethanol (PtE), indicating activation of phospholipase D (PLD). By contrast, this IL-8-dependent PLD activity was undetectable in IL-8-stimulated neutrophils. PLD activation appeared to be downstream of protein kinase C, because several inhibitors abrogated the increase in [H-3]PtE, whereas guanosine-5'-O-(3-thiotriphosphate (GTP(gamma)S) and inositol trisphosphorothioate (IP3S3) both increased the generation of [H-3]PtE. Together, these results demonstrate that the IL-8RB receptor is sufficient to mediate phospholipase C (PLC) and PLD activation in T lymphocytes, but not in neutrophils, and indicate an important difference in receptor usage and signal transduction pathways between IL-8-stimulated lymphocytes and neutrophils. C1 GLAXO INST MOLEC BIOL SA,CH-1211 GENEVA,SWITZERLAND. STANFORD UNIV,DEPT MOLEC PHARMACOL,STANFORD,CA 94305. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP BACON, KB (reprint author), DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,901 CALIF AVE,PALO ALTO,CA 94304, USA. NR 35 TC 58 Z9 58 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 APR 15 PY 1995 VL 154 IS 8 BP 3654 EP 3666 PG 13 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000004 PM 7706709 ER PT J AU FISCHER, AC RUVOLO, PP BURT, R HORWITZ, LR BRIGHT, EC HESS, JM BESCHORNER, WE HESS, AD AF FISCHER, AC RUVOLO, PP BURT, R HORWITZ, LR BRIGHT, EC HESS, JM BESCHORNER, WE HESS, AD TI CHARACTERIZATION OF THE AUTOREACTIVE T-CELL REPERTOIRE IN CYCLOSPORINE-INDUCED SYNGENEIC GRAFT-VERSUS-HOST DISEASE - A HIGHLY CONSERVED REPERTOIRE MEDIATES AUTOAGGRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RAT RADIATION CHIMERA; TREATED RATS; CLONAL DELETION; LYMPHOCYTES-T; RECEPTOR; DETERMINANTS; REQUIREMENT; MECHANISMS; ANTIBODIES; SUBSETS AB Syngeneic graft-vs-host disease (GVHD) is a MHC class II-restricted T cell-mediated autoimmune syndrome that occurs following syngeneic bone marrow transplantation and the administration of cyclosporin (CsA). The present studies evaluated the V beta repertoire of T lymphocytes that mediate SGVHD. To facilitate analysis, SGVHD effector cells were adoptively transferred into thymectomized syngeneic recipients reconstituted with T cell-depleted bone marrow to provide an environment that allows for the selective clonal expansion of autoreactive T cells. Analysis of target tissues and PBL by reverse transcriptase PCR using oligonucleotide V beta-specific primers revealed a predominance of V beta 8.5(+) T cells and a minor population expressing V beta 10. The majority of infiltrating lymphocytes in target tissues was confirmed to be V beta 8.5(+) by in situ hybridization and by immunoperoxidase staining. A small population of V beta 10(+) cells could also be detected. Furthermore, SGVHD effector T splenocytes depleted of lymphocytes expressing either the TCR-alpha beta or the V beta 8.5 determinant could not adoptively transfer SGVHD. Depletion of T cells expressing the V beta 10 determinant delayed the onset of this autoaggression syndrome. Subset analysis of the autoreactive T cell compartment revealed that the V beta 8.5 determinant was expressed on both CD4(+) and CD8(+) lymphocytes whereas the V beta 10 determinant Was principally expressed on a minor population of CD4(+) autoreactive T cells. These data were confirmed by limiting dilution analysis. Additional studies examining the effect of CsA on thymic differentiation revealed that although V beta 8.5 is not normally clonally deleted, there was a pronounced shift in the expression of this determinant between CD4 and CD8 single positive thymocytes, suggesting that CsA may inhibit normal positive selection processes for MHC class I and class II reactive T cells. C1 JOHNS HOPKINS UNIV,CTR ONCOL,DEPT SURG,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,CTR ONCOL,BONE MARROW TRANSPLANT UNIT,BALTIMORE,MD 21287. NHLBI,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA15396]; PHS HHS [A13320, A124319] NR 33 TC 40 Z9 41 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 APR 15 PY 1995 VL 154 IS 8 BP 3713 EP 3725 PG 13 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000010 PM 7706714 ER PT J AU LUCAS, PJ BARE, CV GRESS, RE AF LUCAS, PJ BARE, CV GRESS, RE TI THE HUMAN ANTIMURINE XENOGENEIC CYTOTOXIC RESPONSE .2. ACTIVATED MURINE ANTIGEN-PRESENTING CELLS DIRECTLY STIMULATE HUMAN T-HELPER CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MOLECULES; CTLA-4 COUNTER-RECEPTOR; INTERLEUKIN-2 PRODUCTION; LYMPHOCYTES-T; PROLIFERATIVE RESPONSE; COSTIMULATORY MOLECULE; SPECIES SPECIFICITY; ADHESION MOLECULES; DISTINCT ROLES; CD28 AB Generation of a human T cell anti-murine xenogeneic response has previously been shown to be dependent on presentation of murine Ag by human APC. We have undertaken a series of experiments to better delineate the cellular defects that prevent effective production of IL-2 by human T cells upon direct exposure to murine stimulator populations. It was found that although resting human T cells cannot respond effectively to resting murine APC, they can respond to activated murine stimulator populations. Such APC activation could be mediated by murine granulocyte-macrophage-CSF or LPS that were associated with increased expression of B7-2 on the xenogeneic stimulating cell populations. Blocking studies with Ab provided further evidence that costimulation through CD28 played a critical role in the stimulation of human T cells by activated murine-stimulator cells in the production of IL-2, These results demonstrate the usefulness of this xenogeneic system in understanding human T cell-APC interactions and defining minimally sufficient T cell activation requirements. They further delineate the cellular level of deficient activation in the xenogeneic stimulation of human T cells by murine cell populations, and identify the potential importance of CD28/CTLA4 and its ligands in xenogeneic responses. These observations and concepts have implications for clinical efforts in xenografting. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 42 TC 12 Z9 12 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 APR 15 PY 1995 VL 154 IS 8 BP 3761 EP 3770 PG 10 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000015 PM 7706717 ER PT J AU KAWAKAMI, Y ELIYAHU, S JENNINGS, C SAKAGUCHI, K KANG, XQ SOUTHWOOD, S ROBBINS, PF SETTE, A APPELLA, E ROSENBERG, SA AF KAWAKAMI, Y ELIYAHU, S JENNINGS, C SAKAGUCHI, K KANG, XQ SOUTHWOOD, S ROBBINS, PF SETTE, A APPELLA, E ROSENBERG, SA TI RECOGNITION OF MULTIPLE EPITOPES IN THE HUMAN-MELANOMA ANTIGEN GP100 BY TUMOR-INFILTRATING T-LYMPHOCYTES ASSOCIATED WITH IN-VIVO TUMOR-REGRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL CLONES; MHC MOLECULES; IDENTIFICATION; IMMUNOTHERAPY; RESTRICTION; HLA-A2.1 AB Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag. Adoptive transfer of the four gp 100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one for TIL1143, and two for TIL1200) were recognized by CTL derived from different patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding affinity to HLA-A2.1. These gp100 epitopes may be responsible for mediating tumor rejection in vivo and thus may be useful for the development of immunotherapies for patients with melanoma. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. CYTEL CORP,DEPT IMMUNOL,SAN DIEGO,CA 92121. RP KAWAKAMI, Y (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 45 TC 472 Z9 482 U1 0 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1995 VL 154 IS 8 BP 3961 EP 3968 PG 8 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000036 PM 7706734 ER PT J AU WYNN, TA JANKOVIC, D HIENY, S ZIONCHECK, K JARDIEU, P CHEEVER, AW SHER, A AF WYNN, TA JANKOVIC, D HIENY, S ZIONCHECK, K JARDIEU, P CHEEVER, AW SHER, A TI IL-12 EXACERBATES RATHER THAN SUPPRESSES T-HELPER 2-DEPENDENT PATHOLOGY IN THE ABSENCE OF ENDOGENOUS IFN-GAMMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; MURINE SCHISTOSOMIASIS-MANSONI; LYMPHOCYTE MATURATION FACTOR; INVIVO MOLECULAR ANALYSIS; GRANULOMA-FORMATION; IMMUNE-RESPONSE; MESSENGER-RNA; INFECTED MICE; FACTOR INTERLEUKIN-12; CYTOKINE AB To assess the role of IFN-gamma in the in vivo regulation of Th subset? diferentiation by; IL-12, schistosome egg-induced Th2 responses and granuloma formation were studied in IFN-gamma knock-out (gamma KO) mice in which the absence of endogenous IFN-gamma is assured. Rather than suppressing pathology and eosinophilia as observed in wild-type animals, exogenous IL-12 in egg-injected gamma KO mice exacerbated Th2-dependent granuloma formation while failing to reduce peak tissue eosinophilia. Similarly, instead of inhibiting its production, IL-12 caused a dramatic increase in serum IgE levels in gamma KO animals after egg injection. Although the suppressive effects of IL-12 on Th2 responses were blocked in the absence of IFN-gamma, lymphocyte proliferation and IL-2 production were enhanced, a phenomenon which may underlie the observed exacerbation of egg-induced pathology. These findings formally establish that IL-12 inhibits Th2 development indirectly in vivo through the stimulation of IFN-gamma synthesis. In contrast, its promotion of Th1-associated responses seems to be at least partly a result of the direct action of the cytokine. C1 NIAID,PARASIT DIS LAB,HOST PARASITE RELAT SECT,BETHESDA,MD 20892. GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080. RP WYNN, TA (reprint author), NIAID,IMMUNOL & CELL BIOL SECT,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 44 TC 127 Z9 127 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 APR 15 PY 1995 VL 154 IS 8 BP 3999 EP 4009 PG 11 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000041 PM 7706739 ER PT J AU FUKUYAMA, R RAPOPORT, SI AF FUKUYAMA, R RAPOPORT, SI TI BRAIN-SPECIFIC EXPRESSION OF HUMAN MICROTUBULE-ASSOCIATED PROTEIN-1A (MAP1A) GENE AND ITS ASSIGNMENT TO HUMAN-CHROMOSOME-15 SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE MICROTUBULE-ASSOCIATED PROTEIN; MOLECULAR CLONING; GENE MAPPING; NORTHERN BLOT; BRAIN ID FAMILIAL ALZHEIMERS-DISEASE; ADULT-RAT BRAIN; MESSENGER-RNA; ANTIBODY; CLONING; LOCUS AB We isolated several cDNA fragments by immunoscreening a human cDNA library with our monoclonal antibody, BG5, that showed neuronal staining on human and rat brain sections, A 1,570 bp sequence of one cDNA fragment showed 75% homology to the rat microtubule-associated protein 1A (MAP1A) cDNA sequence. This rat MAP1A-like human cDNA was highly specific to the adult brain among human tissues tested, and was expressed in various brain regions including white matter, The size of the mRNA detected with Northern blot analysis in adult human brain equaled 10 kb. The gene of this cDNA was assigned to human chromosome 15 that has a syntenic region of mouse chromosome 2, where the mouse MAP1A gene has been assigned. These results indicate that this rat MAP1A-like cDNA is a portion of human MAP1A and is a conserved molecular species among humans and rodents, (C) 1995 Wiley-Liss, Inc.* RP FUKUYAMA, R (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892, USA. NR 23 TC 7 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 15 PY 1995 VL 40 IS 6 BP 820 EP 825 DI 10.1002/jnr.490400613 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QW015 UT WOS:A1995QW01500012 PM 7629894 ER PT J AU SACKS, DL KENNEY, RT KREUTZER, RD JAFFE, CL GUPTA, AK SHARMA, MC SINHA, SP NEVA, FA SARAN, R AF SACKS, DL KENNEY, RT KREUTZER, RD JAFFE, CL GUPTA, AK SHARMA, MC SINHA, SP NEVA, FA SARAN, R TI INDIAN KALA-AZAR CAUSED BY LEISHMANIA-TROPICA SO LANCET LA English DT Note ID OPERATION DESERT-STORM AB Kala-azar, or visceral leishmaniasis, in India is generally assumed to be a result of infection with Leishmania donovani. 15 parasite isolates collected over the past 10 years from patients with classical disease were typed by monoclonal antibodies, isoenzymes, and kDNA analysis. 4 were shown to be L tropica, a species historically associated with cutaneous disease and more recently a mild ''visceralising'' disease from the Desert Storm experience. The results confirm that L tropica is a co-endemic agent of visceral leishmaniasis in India, and may shed light on the rising frequency of therapeutic unresponsiveness to sodium antimony gluconate, which complicates treatment of this lethal disease. C1 YOUNGSTOWN STATE UNIV,DEPT BIOL,YOUNGSTOWN,OH. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT PARASITOL,JERUSALEM,ISRAEL. INDIAN COUNCIL MED RES,RAJENDRA MEM RES INST,PATNA,BIHAR,INDIA. RP SACKS, DL (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 7 TC 83 Z9 87 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD APR 15 PY 1995 VL 345 IS 8955 BP 959 EP 961 DI 10.1016/S0140-6736(95)90703-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA QT919 UT WOS:A1995QT91900013 PM 7715298 ER PT J AU BEREZHKOVSKII, AM WEISS, GH AF BEREZHKOVSKII, AM WEISS, GH TI SOME GENERALIZATIONS OF THE TRAPPING PROBLEM SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID DIFFUSION-CONTROLLED REACTIONS; NEAREST-NEIGHBOR DISTANCES; CORRELATED TRAPS; RANDOM-WALKS; KINETICS; NUMBER; DEATH AB We consider two effects on kinetics that have not generally been taken into account in analyses of classical trapping models for the reactions A + T --> T and A --> T --> 0: the effects due to correlations in the initial positions of the A's and those due to the state of mobility of each of the species, Our analysis is formulated in terms of three-dimensional Brownian motion. We give a heuristic treatment of the short-time regime based on statistical properties of the Wiener sausage. The effects of initially correlated positions are modelled in terms of a set of a multiplicity of A particles located at the origin. C1 NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NIDDKD, CHEM PHYS LAB, BETHESDA, MD 20892 USA. LY KARPOV PHYS CHEM RES INST, MOSCOW 103064, RUSSIA. NR 43 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD APR 15 PY 1995 VL 215 IS 1-2 BP 40 EP 50 DI 10.1016/0378-4371(95)00009-V PG 11 WC Physics, Multidisciplinary SC Physics GA QV083 UT WOS:A1995QV08300004 ER PT J AU DING, J DAS, K TANTILLO, C ZHANG, W CLARK, AD JESSEN, S LU, X HSIOU, Y JACOBOMOLINA, A ANDRIES, K PAUWELS, R MOEREELS, H KOYMANS, L JANSSEN, PAJ SMITH, RH KOEPKE, MK MICHEJDA, CJ HUGHES, SH ARNOLD, E AF DING, J DAS, K TANTILLO, C ZHANG, W CLARK, AD JESSEN, S LU, X HSIOU, Y JACOBOMOLINA, A ANDRIES, K PAUWELS, R MOEREELS, H KOYMANS, L JANSSEN, PAJ SMITH, RH KOEPKE, MK MICHEJDA, CJ HUGHES, SH ARNOLD, E TI STRUCTURE OF HIV-1 REVERSE-TRANSCRIPTASE IN A COMPLEX WITH THE NONNUCLEOSIDE INHIBITOR ALPHA-APA-R-95845 AT 2.8-ANGSTROM RESOLUTION SO STRUCTURE LA English DT Article DE AIDS; DRUG RESISTANCE; MECHANISM OF NONNUCLEOSIDE INHIBITION; POLYMERASE STRUCTURE; PROTEIN DRUG INTERACTIONS ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID SUBSTITUTIONS; RIBONUCLEASE-H DOMAIN; NONNUCLEOSIDE INHIBITORS; CRYSTAL-STRUCTURE; NUCLEOTIDE-SEQUENCE; TIBO DERIVATIVES; TYPE-1; RESISTANCE; REPLICATION AB Background: HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that copies the RNA genome of HIV-1 into DNA. It is a heterodimer composed of a 66 kDa (p66) and a 51 kDa (p51) subunit. HIV-1 RT is a crucial target for structure-based drug design, and potent inhibitors have been identified, whose efficacy,however, is limited by drug resistance. Results: The crystal structure of HIV-1 RT in complex with the non-nucleoside inhibitor alpha-anilinophenylacetamide (alpha-APA) R95845 has been determined at 2.8 Angstrom resolution. The inhibitor binds in a hydrophobic pocket near the polymerase active site. The pocket contains five aromatic amino acid residues and the interactions of the side chains of these residues with the aromatic rings of non-nucleoside inhibitors appear to be important for inhibitor binding. Most of the amino acid residues where mutations have been correlated with high levels of resistance to non-nucleoside inhibitors of HIV-1 RT are located close to alpha-APA. The overall fold of HIV-1 RT in complex with alpha-APA is similar to that found when in complex with nevirapine, another non-nucleoside inhibitor, but there are significant conformational changes relative to an HIV-1 RT/DNA/Fab complex. Conclusions: The non-nucleoside inhibitor-binding pocket has a flexible structure whose mobility may be required for effective polymerization, and may be part of a hinge that permits relative movements of two subdomains of the p66 subunit denoted the 'palm' and 'thumb'. An understanding of the structure of the inhibitor-binding pocket, of the interactions between HIV-1 RT and alpha-APA, and of the locations of mutations that confer resistance to inhibitors provides a basis for structure-based design of chemotherapeutic agents for the treatment of AIDS. C1 RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. TIBOTEC,INST ANTIVIRAL RES,B-2650 EDEGEM,BELGIUM. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. FU NCI NIH HHS [N0I CO-74101]; NIAID NIH HHS [AI 36144, AI 27690] NR 69 TC 215 Z9 222 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD APR 15 PY 1995 VL 3 IS 4 BP 365 EP 379 DI 10.1016/S0969-2126(01)00168-X PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QT741 UT WOS:A1995QT74100007 PM 7542140 ER PT J AU LIU, YS GOROSPE, M YANG, CL HOLBROOK, NJ AF LIU, YS GOROSPE, M YANG, CL HOLBROOK, NJ TI ROLE OF MITOGEN-ACTIVATED PROTEIN-KINASE PHOSPHATASE DURING THE CELLULAR-RESPONSE TO GENOTOXIC STRESS - INHIBITION OF C-JUN N-TERMINAL KINASE-ACTIVITY AND AP-1-DEPENDENT GENE ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID IMMEDIATE-EARLY GENE; TYROSINE-PHOSPHATASE; GROWTH; COMPLEX; AP-1; FOS; PRODUCT; 3CH134 AB Irradiation of mammalian cells with short wavelength ultraviolet light (UVC) evokes a cascade of phosphorylation events leading to altered gene expression. Both the classic mitogen-activated protein (MAP) kinases and the distantly related c-Jun N-terminal kinases (JNK) contribute to the response via phosphorylation of transcription factors including AP-1. These kinases are themselves regulated via reversible phosphorylation, and several recently identified specific MAP kinase phosphatases (MKP) have been implicated in down regulating MAP kinase-dependent gene expression in response to mitogens. Here, we provide evidence that MKP-1 plays a role in regulating transcriptional activation in response to UVC as well as another genotoxic agent, methyl methanesulfonate (MMS). We further demonstrate that JNK is a likely target for MKP-1. JNK is shown to be activated by UVC and MMS treatment, while MAP kinase activation occurs only with UVC. Like JNK activation, MKP-1 mRNA is induced by both treatments, and elevated MKP-1 expression coincides with a decline in JNK activity. Constitutive expression of MKP-1 in vivo inhibits JNK activity and reduces UVC- and MMS-induced activation of AP-1-dependent reporter genes. C1 NIA,GENE EXPRESS & AGING SECT,BALTIMORE,MD 21224. RI Liu, Yusen/E-3527-2011 NR 37 TC 253 Z9 255 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 1995 VL 270 IS 15 BP 8377 EP 8380 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800002 PM 7721728 ER PT J AU ZHANG, XL MATHEWS, CK AF ZHANG, XL MATHEWS, CK TI NATURAL DNA PRECURSOR POOL ASYMMETRY AND BASE SEQUENCE CONTEXT AS DETERMINANTS OF REPLICATION FIDELITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID POLYMERASES; GENOME AB Previous studies showed a complex relationship between nucleotide composition of a gene and the rate of the gene's evolutionary variation. We have investigated mechanisms by constructing M13 phagemids containing part of the Escherichia coli lacZ gene, in which an opal codon is flanked either by nine adenine . thymine base pairs on each side, or by nine guanine . cytosine pairs, or by its wild-type sequence context. Reversions or pseudoreversions within the opal codon yield a lacZ alpha-peptide that can undergo alpha-complementation and yield a blue plaque when plated with a chromogenic substrate. When these constructs were replicated in HeLa cell extracts, in the presence of equimolar deoxyribonucleoside triphosphate (dNTP) mixtures, reversion was near background levels in both the AT-rich and GC-rich contexts. By contrast, when the DNAs were replicated at dNTP concentrations approximating those in HeLa cell nuclei, increases over background were seen in all three contexts. Replication of the phagemids in vivo led to even higher mutation frequencies. Replication in the presence of dGMP, added to inhibit proofreading, caused extraordinarily high reversion frequencies in the GC-flanked opal codon. Apparently, dNTP concentrations approximating intracellular concentrations are mildly but significantly mutagenic, and pool asymmetries and base sequence context both contribute to the natural fidelity of DNA replication. C1 OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. NIEHS,RES TRIANGLE PK,NC 27709. NR 15 TC 18 Z9 18 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 APR 14 PY 1995 VL 270 IS 15 BP 8401 EP 8404 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800008 PM 7721732 ER PT J AU BERGANTINO, E DAINESE, P CEROVIC, Z SECHI, S BASSI, R AF BERGANTINO, E DAINESE, P CEROVIC, Z SECHI, S BASSI, R TI A POSTTRANSLATIONAL MODIFICATION OF THE PHOTOSYSTEM-II SUBUNIT CP29 PROTECTS MAIZE FROM COLD STRESS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHLOROPHYLL-A/B-PROTEINS; CHLOROPLAST PSBA GENE; CYTOCHROME-BF COMPLEX; THYLAKOID MEMBRANES; CHLAMYDOMONAS-REINHARDTII; LATERAL REDISTRIBUTION; ELECTRON-TRANSPORT; INVIVO DEGRADATION; STATE TRANSITIONS; BINDING PROTEINS AB The resistance of maize plants to cold stress has been associated with the appearance of a new chlorophyll a/b binding protein in the thylakoid membrane following chilling treatment in the light. The cold-induced protein has been isolated, characterized by amino acid sequencing, and pulse labeled with radioactive precursors, showing that it is the product of post-translational modification by phosphorylation of the minor chlorophyll a/b protein CP29 rather than the product of a cold-regulated gene or an unprocessed CP29 precursor. We show here that the CP29 kinase activity displays unique characteristics differing from previously described thylakoid kinases and is regulated by the redox state of a quinonic site. Finally, we show that maize plants unable to perform phosphorylation have enhanced sensitivity to cold-induced photoinhibition. C1 UNIV PADUA,DIPARTIMENTO BIOL,I-35121 PADUA,ITALY. CTR UNIV PARIS SUD,UTILISAT RAYONNEMENT ELECTROMAGNET LAB,F-91405 ORSAY,FRANCE. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV VERONA,FAC SCI MATEMAT FIS & NAT,I-37134 VERONA,ITALY. OI bassi, roberto/0000-0002-4140-8446 NR 47 TC 98 Z9 101 U1 0 U2 6 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 APR 14 PY 1995 VL 270 IS 15 BP 8474 EP 8481 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800019 PM 7721743 ER PT J AU WOLFF, EC LEE, YB CHUNG, SI FOLK, JE PARK, MH AF WOLFF, EC LEE, YB CHUNG, SI FOLK, JE PARK, MH TI DEOXYHYPUSINE SYNTHASE FROM RAT TESTIS - PURIFICATION AND CHARACTERIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INITIATION-FACTOR EIF-4D; POSTTRANSLATIONAL FORMATION; SACCHAROMYCES-CEREVISIAE; HYPUSINE FORMATION; PROTEIN; SPERMIDINE; POLYAMINES; CELLS; IDENTIFICATION; PROLIFERATION AB Deoxyhypusine synthase is the first enzyme involved in the post translational formation of hypusine, a unique amino acid that occurs at one position in a single cellular protein, eukaryotic translation initiation factor 5A (eIF-5A). This NAD-dependent enzyme catalyzes the formation of deoxyhypusine by transfer of the butylamine portion of spermidine to the epsilon-amino group of a specific lysine residue in the eIF-5A precursor. Its purification from rat testis was accomplished by ammonium sulfate fractionation and successive ion-exchange chromatographic steps, followed by chromatofocusing on a hydrophilic resin (Mono P). A pI of 4.7 was determined by isoelectric focusing, Amino acid sequences of five tryptic peptides of the pure enzyme did not correspond to any sequences in the protein data banks. The enzyme migrates as a single band ton SDS-polyacrylamide gel electrophoresis with an apparent monomer molecular mass of similar to 42,000 Da. Matrix-assisted laser desorption mass spectrometry gave a monomer mass of 40,800 Da. There is evidence, however, that the active enzyme exists as a tetramer of this subunit. Rabbit polyclonal antibodies to the 42-kDa protein precipitated deoxyhypusine synthase activity. The enzyme shows a strict specificity for NAD. Purified deoxyhypusine synthase catalyzes the overall synthesis of deoxyhypusine and, in the absence of the eIF-5A precursor, catalyzes the cleavage of spermidine. RP WOLFF, EC (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BLDG 30,RM 211,30 CONVENT DR,MSC 4330,BETHESDA,MD 20892, USA. NR 37 TC 44 Z9 46 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 APR 14 PY 1995 VL 270 IS 15 BP 8660 EP 8666 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800046 PM 7721768 ER PT J AU COOL, DR FENGER, M SNELL, CR LOH, YP AF COOL, DR FENGER, M SNELL, CR LOH, YP TI IDENTIFICATION OF THE SORTING SIGNAL MOTIF WITHIN PROOPIOMELANOCORTIN FOR THE REGULATED SECRETORY PATHWAY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; B SECRETOGRANIN-I; DISULFIDE BOND; PROTEIN; CELLS; PROOPIOMELANOCORTIN; PITUITARY; GRANULES; PEPTIDES; AGGREGATION AB The NH2-terminal region of pro-opiomelanocortin (POMC) is highly conserved across species, having two disulfide bridges that cause the formation of an amphipathic hairpin loop structure between the 2nd and 3rd cysteine residues (Cys(8) to Cys(20)). The role that the NH2-terminal region of pro-opiomelanocortin plays in acting as a molecular sorting signal for the regulated secretory pathway was investigated by using site-directed mutagenesis either to disrupt one or more of the disulfide bridges or to delete the amphipathic loop entirely. When POMC was expressed in Neuro-2a cells, ACTH immunoreactive material was localized in punctate secretory granules in the cell body and along the neurites, with heavy labeling at the tips. ACTH was secreted from these POMC-transfected cells in a regulated manner. Disruption of both disulfide bridges or the second disulfide bridge or removal of the amphipathic hairpin loop resulted in constitutive secretion of the mutant POMC from the cells and a lack of punctate secretory granule immunostaining within the cells. We have modeled the NH2-terminal POMC Cys(8) to Cys(20) domain and have identified it as an amphipathic loop containing four highly conserved hydrophobic and acidic amino acid residues (Asp(10)-Leu(11)-Glu(14)-Leu(18)). Thus the sorting signal for POMC to the regulated secretory pathway appears to be encoded by a specific conformational motif comprised of a 13-amino acid amphipathic loop structure stabilized by a disulfide bridge, located at the NH2 terminus of the molecule. C1 SANDOZ INST MED RES, LONDON WC1E 6BN, ENGLAND. RP COOL, DR (reprint author), NICHHD, DEV NEUROBIOL LAB, CELLULAR NEUROBIOL SECT, BLDG 49, RM 5A38, BETHESDA, MD 20892 USA. NR 38 TC 128 Z9 129 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 APR 14 PY 1995 VL 270 IS 15 BP 8723 EP 8729 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800055 PM 7721777 ER PT J AU LEE, CH MURAKAMI, T SIMONDS, WF AF LEE, CH MURAKAMI, T SIMONDS, WF TI IDENTIFICATION OF A DISCRETE REGION OF THE G-PROTEIN GAMMA-SUBUNIT CONFERRING SELECTIVITY IN BETA-GAMMA COMPLEX-FORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING REGULATORY PROTEINS; INFECTED INSECT CELLS; LIMITED PROTEOLYSIS; COILED-COIL; TRANSDUCIN; DIMERS; PURIFICATION; EXPRESSION; SEQUENCE; BRAIN AB The identification of multiple G protein beta and gamma subunit subtypes suggests a potential diversity of beta gamma heterodimers, which may contribute to the specificity of signal transduction between receptors and effecters. The assembly of beta and gamma subtypes is selective. For example, gamma(1) can assemble with beta(1) but not with beta(2), whereas gamma(2) assembles with both beta isoforms. To identify the structural features of the beta and gamma subunits governing selectivity in heterodimer assembly, a series of nonisoprenylated chimeras of gamma(1) and gamma 2 was constructed, and their interaction with beta(1) and beta(2) was assessed by their ability to direct beta expression to the cytosol in cotransfected COS cells. All of the gamma(1)/gamma(2) chimeras were capable of interacting with beta(1) as judged by the cotransfection assay. Chimeras containing gamma(2) sequence near the middle of the molecule between two conserved sequence motifs were capable of interacting as well with beta(2). Among 12 divergent residues in this region, it was found that replacement of three consecutive amino acids in gamma(1), Glu-Glu-Phe (residues 38-40), with the three corresponding amino acids of gamma(2), Ala-Asp-Leu (residues 35-37), conferred the ability to assemble with beta(2). The reciprocal chimera containing Glu-Glu-Phe in the context of gamma(2) failed to assemble with beta(2). The last residue of this triplet is occupied by a leucine in all known mammalian gamma subunits except gamma(1) and appears to be a key determinant of the ability of a gamma subunit to assemble with beta(2). This locus maps to a region of predicted alpha-helical structure in the gamma subunit, likely to represent a point of physical contact with the beta subunit. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. NR 52 TC 35 Z9 35 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 APR 14 PY 1995 VL 270 IS 15 BP 8779 EP 8784 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800062 PM 7721784 ER PT J AU OBIRI, NI DEBINSKI, W LEONARD, WJ PURI, RK AF OBIRI, NI DEBINSKI, W LEONARD, WJ PURI, RK TI RECEPTOR FOR INTERLEUKIN-13 - INTERACTION WITH INTERLEUKIN-4 BY A MECHANISM THAT DOES NOT INVOLVE THE COMMON GAMMA-CHAIN SHARED BY RECEPTORS FOR INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, INTERLEUKIN-9 AND INTERLEUKIN-15 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN B-CELLS; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; IGE SYNTHESIS; KILLER-CELLS; EXPRESSION; CYTOKINE; DIFFERENTIATION; PROLIFERATION; ACTIVATION AB Interleukin 13 (IL-13) shares many biological properties with IL-4, and although the receptor for IL-4 (IL-4R) has been characterized, the expression and structure of IL-13 receptor are unknown. We report here that human renal cell carcinoma (RCC) cells express large numbers of functional IL-13R. Human B lymphocytes and monocytes expressed a very small number of IL-13R, while resting or activated human T cells expressed little or no IL-13R, IL-4 did not compete for IL-13 binding, while IL-13 competed for IL-4 binding, even though IL-4R and IL-13R are structurally distinct on human RCC cells. IL-13 cross-linked with one major protein that is similar in size to the gamma(c) subunit of IL-2, -4, -7, -9, and -15 receptors but was not recognized by anti-gamma(c) or anti-IL-4R antibodies. IL-4, on the other hand, cross linked with two major proteins, the smaller of which appears to be similar in size to IL-13R and gamma(c), but (like the IL-13R) it did not react with anti-gamma(c) antibody. Although as shown in this study and in previous studies, gamma(c) is a functional component of IL-4R in lymphoid cells, it does not appear to be associated with IL-4R on RCC cells. Even in the absence of common gamma chain IL-4 and IL-13 were able to up-regulate intracellular adhesion molecule-1 antigen on RCC cells. These data suggest that the interaction of IL-13 with IL-4R does not involve gamma(c) and IL-13R itself may be a novel subunit of the IL-4R. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 31 TC 229 Z9 234 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 1995 VL 270 IS 15 BP 8797 EP 8804 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800064 PM 7721786 ER PT J AU FONSECA, MI BUTTON, DC BROWN, RD AF FONSECA, MI BUTTON, DC BROWN, RD TI AGONIST REGULATION OF ALPHA(1B)-ADRENERGIC RECEPTOR SUBCELLULAR-DISTRIBUTION AND FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; SMOOTH-MUSCLE CELLS; DDT1 MF-2 CELLS; ALPHA-1-ADRENERGIC RECEPTOR; MOLECULAR-CLONING; INTRACELLULAR CA-2+; DESENSITIZATION; SUBTYPES; CDNA; EXPRESSION AB We have monitored agonist-induced alpha(1B)-adrenergic receptor (alpha(1B)AR) redistribution by immunocytochemical procedures in concert with functional measurements of agonist-elicited [H-3]inositol phosphate (InsP) production in human embryonal kidney 293 cells stably expressing alpha(1B)AR cDNA (HEK293/alpha(1B)). Anti-peptide antibodies directed against the carboxyl-terminal decapeptide of the alpha(1B)AR were prepared and shown to react specifically with alpha(1B)AR on immunoblots and in situ in HEK293/alpha(1B) transfectants. Treatment of HEK293/alpha(1B) cells with norepinephrine (10 mu M) results in a rapid (5-15 min) and striking internalization of cell surface receptor as visualized by confocal immunofluorescence microscopy. Receptor redistribution is sustained in the presence of agonist, rapidly reversed upon agonist removal, and prevented by the alpha(1) antagonist prazosin. Receptor internalizes to endosomes, as shown by colocalization with transferrin receptor, an endosomal marker. Activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (50 nM) causes receptor endocytosis similar to agonist; agonist-induced internalization is blocked by the PKC inhibitor staurosporine (0.5 mu M). In parallel experiments, agonist-induced [H-3]InsP production is abolished by phorbol 12-myristate 13-acetate but potentiated by staurosporine. Inhibition of receptor internalization with hypertonic sucrose attenuates agonist-induced [H-3]InsP formation; this effect is reversed by concomitant inhibition of PKC with staurosporine. These results suggest that PKC-dependent phosphorylation occurring as a consequence of alpha(1)AR stimulation induces receptor desensitization and internalization. Internalized receptor is reactivated and continuously recycled to the cell surface during agonist exposure. C1 UNIV ILLINOIS,DEPT PHARMACOL MC 868,CHICAGO,IL 60612. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 41470] NR 50 TC 87 Z9 89 U1 2 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 APR 14 PY 1995 VL 270 IS 15 BP 8902 EP 8909 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800077 PM 7721798 ER PT J AU BURKE, TR BARCHI, JJ GEORGE, C WOLF, G SHOELSON, SE YAN, XJ AF BURKE, TR BARCHI, JJ GEORGE, C WOLF, G SHOELSON, SE YAN, XJ TI CONFORMATIONALLY CONSTRAINED PHOSPHOTYROSYL MIMETICS DESIGNED AS MONOMERIC SRC HOMOLOGY-2 DOMAIN INHIBITORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHORYLATED PEPTIDES; SH2 DOMAIN; BINDING; RECOGNITION; P56(LCK); TARGETS; KINASE AB Inhibitors of specific src homology 2 (SH2) domain binding interactions could potentially afford new therapeutic approaches toward a variety of diseases, including several cancers. To date SH2 domain inhibitors have been confined to small phosphotyrosyl (pTyr)-containing peptides that appear to bind along the surface of SH2 domains with specific recognition features protruding into the protein. Among these protrusions is the pTyr residue itself, which is inserted into a well-formed binding pocket. In the present study monomeric pTyr mimetics were prepared having key aspects of their structure constrained to conformations of the bound pTyr residue observed in the previously reported X-ray structure of a pTyr-peptide bound to the Lck SH2 domain. The resulting constrained pTyr mimetics were examined for inhibitory potency ih six SH2 domain constructs: Lck, Src, Grb2, and the C-terminal SH2 domains of PLC gamma (PLC gamma-C) and the p85 subunit of PI-3 kinase (p85-C), as well as the N-terminal SH2 domain of SH PTP2. Although inhibition constants were in the millimolar range, it was observed that capping pTyr as its N-alpha-acetyl carboxamide [(L)-1] provided a roughly 2-3-fold increase in potency relative to free pTyr. Diastereomeric indanylglycine-based analogues (+/-)-3a,b were essentially inactive. Of note was methanobenzazocine (+/-)-2. While being racemic and a partial pTyr structure, this analogue retained full binding potency of the enantiomerically pure N-alpha-acetyl pTyr amide (L)-1. Modification and elaboration of 2 could potentially result in small molecule inhibitors having greater potency. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014; Burke, Terrence/N-2601-2014 NR 47 TC 62 Z9 62 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 14 PY 1995 VL 38 IS 8 BP 1386 EP 1396 DI 10.1021/jm00008a017 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QU380 UT WOS:A1995QU38000017 PM 7537333 ER PT J AU JONES, BCNM SILVERTON, JV SIMONS, C MEGATI, S NISHIMURA, H MAEDA, Y MITSUYA, H ZEMLICKA, J AF JONES, BCNM SILVERTON, JV SIMONS, C MEGATI, S NISHIMURA, H MAEDA, Y MITSUYA, H ZEMLICKA, J TI SYNTHESIS, ABSOLUTE-CONFIGURATION, AND ENANTIOSELECTIVITY OF ANTIRETROVIRAL EFFECT OF (R)-(-)-CYTALLENE AND (S)-(+)-CYTALLENE - LIPASE-CATALYZED ENANTIOSELECTIVE ACYLATIONS OF (+/-)-N-4-ACYLCYTALLENES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DERIVATIVES; PROTECTION; ANALOGS; INVITRO; ESTERS AB Enantioselectivity of acylations of (+/-)-cytallene (1b), (+/-)-N-4-acetylcytallene (11a), (+/-)-N-4-benzoylcytallene (11b), and (+/-)-N-4-(9-fluorenylmethoxycarbonyl)cytallene (11c) using vinyl butyrate or acetate catalyzed by lipases in organic solvents was investigated. Reactions with 1b, 11a, and adenallene (1a) did not display a high enantioselectivity but all resulted in a predominant acylation of the (-)-enantiomers. Application of the Lowe-Brewster rule led to a tentative assignment of the R-configuration to all acylated products. Studies of the time course of acylation of (+/-)-N-4-benzoylcytallene (11b) in chloroform, tetrahydrofuran (THF), tetrahydropyran (THP), tetrahydrothiophene (THT), and dioxane with lipase PS30 and/or AK showed that the reaction in THF catalyzed by lipase AK was the most promising for resolution of 11b. Indeed, a large-scale acylation afforded, after separation and deprotection of intermediates 3e and 10d, (+)- and (-)-cytallene (3c and 2b) in high yield and enantioselectivity. Acylation of 11c in THF led also to formation of 3c and 2b in high enantioselectivity. Single crystal X-ray diffraction established the S-configuration of (+)-cytallene (3c), thus confirming the assignment made on the basis of Lowe-Brewster rule. An improved large-scale synthesis of (+/-)-cytallene (1b) is also described. The R-enantiomer 2b inhibited the replication of a primary human immunodeficiency virus (HIV-1) isolate in phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBM) with IC50 0.4 and IC90 1.7 mu M. (+/-)-Cytallene (1b) exhibited IC50 0.8 and IC90 3.4 mu M. Both compounds completely suppressed replication of HIV-1 at 10 mu M with no detectable cytotoxicity. The S-enantiomer (3c) was inactive. C1 WAYNE STATE UNIV,SCH MED,MICHIGAN CANC FDN,DEPT CHEM,DEV THERAPEUT PROGRAM,DETROIT,MI 48201. NHLBI,BETHESDA,MD 20892. CHIRAL TECHNOL INC,EXTON,PA 19341. NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. RI Simons, Claire/N-5788-2014 OI Simons, Claire/0000-0002-9487-1100 FU NCI NIH HHS [CA32779] NR 33 TC 40 Z9 40 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 14 PY 1995 VL 38 IS 8 BP 1397 EP 1405 DI 10.1021/jm00008a018 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QU380 UT WOS:A1995QU38000018 PM 7731024 ER PT J AU KIM, MG ZHURKIN, VB JERNIGAN, RL CAMERINIOTERO, RD AF KIM, MG ZHURKIN, VB JERNIGAN, RL CAMERINIOTERO, RD TI PROBING THE STRUCTURE OF A PUTATIVE INTERMEDIATE IN HOMOLOGOUS RECOMBINATION - THE 3RD STRAND IN THE PARALLEL DNA TRIPLEX IS IN CONTACT WITH THE MAJOR GROOVE OF THE DUPLEX SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HOMOLOGOUS RECOMBINATION; RECA; TRIPLEX DNA; FOOTPRINTING; ISOSTERIC SUBSTITUTION ID COLI RECA PROTEIN; ESCHERICHIA-COLI; 3-STRANDED DNA; BINDING PROTEIN; GENETIC-RECOMBINATION; EXCHANGE PROTEINS; BRANCH MIGRATION; ATP HYDROLYSIS; REPLACING DA; HUMAN-CELLS AB A three-stranded DNA that is a putative intermediate of homologous recombination is a novel DNA tripler, R-form DNA. In R-form DNA the third strand includes both purines and pyrimidines and is parallel to the identical strand of the duplex. To test and refine our previously proposed R-form base triplets we have used two approaches: (1) dimethyl sulfate protection of R-form DNA; and (2) thermal dissociation of R-form DNAs in which the duplex strands were substituted in a strand-specific manner with either 7-deaza-guanine or 7-deaza-adenine. Together, the footprinting and isosteric substitution results demonstrate that the third strand in R-form DNA is in contact with the purines in the N-7 position in the major groove of the Watson-Crick duplex in three ((GC):G, (AT):A and (TA):T) out of the four possible triplets. Furthermore, these results suggest that the N-7 positions of the duplex play a significant role in stabilizing the DNA-DNA contacts during the homology recognition process. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NCI,MATH BIOL LAB,MOLEC STRUCT SECT,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 NR 52 TC 35 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 14 PY 1995 VL 247 IS 5 BP 874 EP 889 DI 10.1006/jmbi.1994.0187 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT129 UT WOS:A1995QT12900005 PM 7723038 ER PT J AU KONDO, H LANE, MA YONEZAWA, Y INGRAM, DK CUTLER, RG ROTH, GS AF KONDO, H LANE, MA YONEZAWA, Y INGRAM, DK CUTLER, RG ROTH, GS TI EFFECTS OF AGING AND DIETARY RESTRICTION ON ACTIVITY OF MONKEY SERUM IN PROMOTING FIBROBLAST MIGRATION SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE AGING; DIETARY RESTRICTION; MONKEY SERUM; FIBROBLAST MIGRATION; MIGRATION INHIBITION ID SKIN FIBROBLASTS; HUMAN-LUNG; GROWTH; AGES; PROLIFERATION; INHIBITION; INTERFERON; LONGEVITY; WOUNDS; YOUNG AB In order to determine whether serum modified cellular aging in vivo, we previously studied the effects of serum from various mammals of different ages on cell functions such as proliferation and migration, and reported that cell migration was more greatly inhibited by serum from old donors than cell proliferation [1]. Moreover, since dietary restriction has been reported to extend lifespan and slow the aging rate of some animals [2], we wondered whether sera from dietary restricted and control monkeys of various ages might exhibit reduced aging effects on cell migration. When serum from young adult (3-5 years old) monkeys was added to plain medium, the migration of human fetal skin fibroblasts was very strongly inhibited compared to FBS. Surprisingly, sera from adult (6-11 years old) and old (more than 18 years old) monkeys caused significantly less migration-inhibitory activity than serum from young adult monkeys although sera from adult and old monkeys were much more inhibitory to cell migration than FBS. Dietary restriction only caused marginal effects on serum migration-promoting activity in a few monkey groups. The inhibition of cell migration caused by monkey serum was not brought about by cytotoxic effects since monkey serum stimulated cell proliferation as well as fetal bovine serum. These results indicate that the effects of aging on monkey serum migration-promoting activity are much more pronounced than those of dietary restriction. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. RP KONDO, H (reprint author), TOKYO METROPOLITAN INST GERNOTOL,DEPT EXPTL BIOL,ITABASHI KU,35-2 SAKAE,TOKYO 173,JAPAN. NR 30 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD APR 14 PY 1995 VL 79 IS 2-3 BP 141 EP 150 DI 10.1016/0047-6374(94)01555-Z PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA QW309 UT WOS:A1995QW30900005 PM 7616765 ER PT J AU CLARKSON, RB NORBY, SW SMIRNOV, A BOYER, S VAHIDI, N NIMS, RW WINK, DA AF CLARKSON, RB NORBY, SW SMIRNOV, A BOYER, S VAHIDI, N NIMS, RW WINK, DA TI DIRECT MEASUREMENT OF THE ACCUMULATION AND MITOCHONDRIAL CONVERSION OF NITRIC-OXIDE WITHIN CHINESE-HAMSTER OVARY CELLS USING AN INTRACELLULAR ELECTRON-PARAMAGNETIC-RESONANCE TECHNIQUE SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE NITRIC OXIDE; FUSINITE; KINETICS; EPR; IN VIVO MEASUREMENT; CHO CELL; CELL METABOLISM; MITOCHONDRION ID NITROGEN-OXIDES; OXIDATION; KINETICS; RELEASE; NO; PEROXYNITRITE; AUTOXIDATION; INHIBITION; REDUCTION; INVIVO AB We have developed an electron paramagnetic resonance (EPR) method for the nondestructive detection and quantification of intracellular NO in real time. Based upon this technique, we have obtained evidence for the metabolism of this bioregulatory molecule by mitochondria. Line-broadening of the EPR signal of a coal derivative, fusinite, was calibrated as a function of NO concentration in aqueous solution. The methodology was validated using two compounds which release NO in a controlled and predictable manner with first-order rate constants k(1) = 5.0 . 10(-3) s(-1) and k(1) = 3.4 . 10(-4) s(-1) (35 degrees C). Fusinite was internalized in Chinese hamster ovary cells (CHO) by phagocytosis, after which the cells were allowed to consume the available O-2, producing an hypoxic environment. The NO released from one of the NO donors, added to the culture fluid at an initial concentration of 50 mu M, was directly measured in the intracellular environment as line-broadening of the fusinite EPR signal. The linewidth diminished with time, indicating that NO was being converted to a non-paramagnetic species by the cells with an apparent zero-order rate constant of 5 . 10(8) NO molecules cell(-1) min(-1) (20 degrees C). Addition of cyanide to the culture medium (5 mM final concentration) inhibited this disappearance of NO. NO also was converted in the presence of isolated mitochondria in the absence of oxygen. These observations suggest that under hypoxic conditions, there exists in CHO cells a metabolic pathway for the conversion of NO to diamagnetic species, which involves interactions with mitochondria. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. RP CLARKSON, RB (reprint author), UNIV ILLINOIS,ILLINOIS EPR RES CTR,URBANA,IL 61801, USA. RI Smirnov, Alex/Q-9818-2016 OI Smirnov, Alex/0000-0002-0037-2555 FU NCRR NIH HHS [RR01811]; NIGMS NIH HHS [GM42208] NR 34 TC 46 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD APR 13 PY 1995 VL 1243 IS 3 BP 496 EP 502 DI 10.1016/0304-4165(94)00181-V PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QT563 UT WOS:A1995QT56300030 PM 7727525 ER PT J AU WALLQVIST, A COVELL, DG AF WALLQVIST, A COVELL, DG TI COOPERATIVITY OF WATER-SOLUTE INTERACTIONS AT A HYDROPHILIC SURFACE SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; MONTE-CARLO SIMULATION; LIQUID WATER; AQUEOUS-SOLUTION; SOLVATION THERMODYNAMICS; HYDROPHOBIC INTERACTION; PROTEIN HYDRATION; BIO-POLYMERS; MEAN FORCE; WALLS AB We have measured the reversible work required to assemble different sets of weak model charges at a water/wall interface using molecular dynamics methods and free energy perturbation techniques. It is found that water is a strong mediator of like-charge repulsive forces due to the ability of water molecules to adopt low free energy configurations that maximize the water-ion interaction while minimizing the penalty of the concomitant water rearrangement. The cooperativity of this mechanism is enhanced at smaller charge separations, but is not associated with any strong preferential hydration structure. The presence of solvent-stabilized, like-charge-charge pairs embedded on a surfaces implies an additional mechanism by which water can stabilize biomolecular assemblies. RP WALLQVIST, A (reprint author), NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. NR 55 TC 3 Z9 3 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD APR 13 PY 1995 VL 99 IS 15 BP 5705 EP 5712 DI 10.1021/j100015a063 PG 8 WC Chemistry, Physical SC Chemistry GA QT465 UT WOS:A1995QT46500063 ER PT J AU HE, X SAINTJEANNET, JP WOODGETT, JR VARMUS, HE DAWID, IB AF HE, X SAINTJEANNET, JP WOODGETT, JR VARMUS, HE DAWID, IB TI GLYCOGEN-SYNTHASE KINASE-3 AND DORSOVENTRAL PATTERNING IN XENOPUS EMBRYOS SO NATURE LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; MESODERM INDUCTION; SPEMANN ORGANIZER; VENTRALIZING FACTOR; AXIAL MESODERM; BODY AXIS; EXPRESSION; DROSOPHILA; WINGLESS; XWNT-8 AB Glycogen synthase kinase 3 (GSK-3) is homologous to the product of the Drosophila gene shaggy (zeste-white 3), which is required for signalling by wingless during Drosophila development. To test whether GSK-3 is also involved in vertebrate pattern formation, its role was investigated during early Xenopus development. It was found that dominant-negative GSK-3 mutants induced dorsal differentiation, whereas wild-type GSK-3 induced ventralization. These results indicate that GSK-3 is required for ventral differentiation, and suggest that dorsal differentiation may involve the suppression of GSK-3 activity by a wingless/wnt-related signal. C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. RP HE, X (reprint author), NCI,VARMUS LAB,BLDG 49,ROOM 4A56,BETHESDA,MD 20892, USA. RI Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 NR 50 TC 415 Z9 418 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 13 PY 1995 VL 374 IS 6523 BP 617 EP 622 DI 10.1038/374617a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QT189 UT WOS:A1995QT18900051 PM 7715701 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI ANSWERS TO THE ANTIPHOSPHOLIPID-ANTIBODY SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MOLECULAR-WEIGHT HEPARIN; FETAL LOSS; PREVENTION RP LOCKSHIN, MD (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 12 TC 66 Z9 67 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 APR 13 PY 1995 VL 332 IS 15 BP 1025 EP 1027 DI 10.1056/NEJM199504133321510 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA QT737 UT WOS:A1995QT73700010 PM 7885409 ER PT J AU KOTTKE, TE TRAPP, MA FORES, MM KELLY, AW JUNG, SH NOVOTNY, PJ PANSER, LA AF KOTTKE, TE TRAPP, MA FORES, MM KELLY, AW JUNG, SH NOVOTNY, PJ PANSER, LA TI CANCER SCREENING BEHAVIORS AND ATTITUDES OF WOMEN IN SOUTHEASTERN MINNESOTA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OLDER WOMEN; MAMMOGRAPHY; PHYSICIANS; SMEAR AB Objectives.-To determine the rates at which women received screening Papanicolaou tests, clinical breast examinations, and mammography and to determine the extent to which these women might be expected to respond to screening recommendations from their physicians. Design.-Random-digit-dial telephone interviews conducted in January 1993. Setting.-Fifteen counties in southeastern Minnesota. Subjects.-A sample of 1019 women who completed the telephone interview. Main Outcome Measures.-Self-reported Papanicolaou test, clinical breast examination, acid mammography screening rates, with verification from medical records for a randomly selected subsample of 200 respondents who reported having had a test within 1 year of the interview. Results.-For women aged 18 years and older, 60% (95% confidence interval, +/-3.4%) reported having had a Papanicolaou test within the preceding year. For women 40 years of age and older, 57% (95% confidence interval, +/-3,5%) reported having had a clinical breast examination in the past year, and 46% (95% confidence interval, +/-3,6%) reported having had a screening mammogram within 1 year. The verified 1-year Papanicolaou test and mammogram rates were 35% and 33%, respectively. More than 90% of the respondents expressed a willingness to have these tests if their physicians were to advise them that the tests were indicated. However, 53% and 54% of the respondents, respectively, said that they either did not care or did not want their physicians to remind them when they were due for a Papanicolaou test or a mammogram. Conclusions.-Although self-reported screening rates in this population meet Healthy People 2000 goals, verified rates were significantly below target levels. A substantial proportion of women in this population remain ambivalent about participating in cancer detection programs. RP KOTTKE, TE (reprint author), MAYO CLIN & MAYO FDN,NCI,DESIGNATED MAYO COMPREHENS CANC CTR,HARWICK 6,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA 57825] NR 30 TC 61 Z9 62 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 12 PY 1995 VL 273 IS 14 BP 1099 EP 1105 DI 10.1001/jama.273.14.1099 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QR059 UT WOS:A1995QR05900028 PM 7707597 ER PT J AU CHEATHAM, TE MILLER, JL FOX, T DARDEN, TA KOLLMAN, PA AF CHEATHAM, TE MILLER, JL FOX, T DARDEN, TA KOLLMAN, PA TI MOLECULAR-DYNAMICS SIMULATIONS ON SOLVATED BIOMOLECULAR SYSTEMS - THE PARTICLE MESH EWALD METHOD LEADS TO STABLE TRAJECTORIES OF DNA, RNA, AND PROTEINS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID UBIQUITIN; PROTEASE C1 UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143. NIEHS,RES TRIANGLE PK,NC 27709. NR 23 TC 445 Z9 452 U1 3 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 12 PY 1995 VL 117 IS 14 BP 4193 EP 4194 DI 10.1021/ja00119a045 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA QT132 UT WOS:A1995QT13200045 ER PT J AU HERMAN, EH HASINOFF, BB ZHANG, J RALEY, LG ZHANG, TM FUKUDA, Y FERRANS, VJ AF HERMAN, EH HASINOFF, BB ZHANG, J RALEY, LG ZHANG, TM FUKUDA, Y FERRANS, VJ TI MORPHOLOGIC AND MORPHOMETRIC EVALUATION OF THE EFFECT OF ICRF-187 ON BLEOMYCIN-INDUCED PULMONARY TOXICITY SO TOXICOLOGY LA English DT Article DE BLEOMYCIN; BLEOMYCIN IRON COMPLEX; PULMONARY TOXICITY; ICRF-187, PROTECTIVE EFFECTS ID INDUCED LUNG FIBROSIS; DEFEROXAMINE INFUSION; CHELATING-AGENTS; MICE; DNA; (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; CARDIOTOXICITY; DEGRADATION; HYDROLYSIS; ADRIAMYCIN AB Morphologic and morphometric studies were made of the protective effects of ICRF-I87 against the pulmonary damage induced by bleomycin in male and female C57/BL6 mice, Sixty minutes prior to the subcutaneous administration of 15 mg/kg of bleomycin, animals received either saline or ICRF-187 (300 or 150 mg/kg) intraperitoneally, twice a week for 4 weeks, The lungs of animals treated with bleomycin alone showed inflammation, hyperplasia of type II epithelial cells, squamous cell metaplasia and fibrosis. The extent of fibrosis was quantified by means of a color videometric system and histologic sections of lung stained according to a modified Masson trichrome method. The severity of these alterations, particularly of fibrosis, was reduced in all groups of animals pretreated with ICRF-187. The fibrosis was reduced to a similar extent in female mice treated with the 300 mg/kg and the 150 mg/kg doses of ICRF-187, from 39.3% to 17.6% and 13.3%, respectively. ICRF-187 induced significantly different degrees of reduction in fibrosis in the 2 groups of male mice treated with the 150 mg/kg and the 300 mg/kg doses, from 30% to 19.7% and 12.2%, respectively. In vitro studies indicated that both ICRF-187 and its open-ring hydrolysis product (ADR-925) remove iron slowly from the bleomycin-iron complex, This observation provides a basis for the concept that ICRF-187 protects by chelating iron involved in the formation of the bleomycin-Fe3+ complex that generates reactive oxygen radicals capable of causing pulmonary damage. C1 UNIV MANITOBA,FAC PHARM,WINNIPEG,MB R3T 2N2,CANADA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIPPON MED COLL,DEPT PATHOL 1,TOKYO,JAPAN. RP HERMAN, EH (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,HFD-472 MOD 1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 44 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 12 PY 1995 VL 98 IS 1-3 BP 163 EP 175 DI 10.1016/0300-483X(94)02987-6 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QX943 UT WOS:A1995QX94300017 PM 7537925 ER PT J AU MAHANEY, JE FROEHLICH, JP THOMAS, DD AF MAHANEY, JE FROEHLICH, JP THOMAS, DD TI CONFORMATIONAL TRANSITIONS OF THE SARCOPLASMIC-RETICULUM CA-ATPASE STUDIED BY TIME-RESOLVED EPR AND QUENCHED-FLOW KINETICS SO BIOCHEMISTRY LA English DT Article ID CALCIUM ADENOSINE-TRIPHOSPHATASE; ELECTRON-PARAMAGNETIC RESONANCE; ADP-INSENSITIVE PHOSPHOENZYME; IODOACETAMIDE SPIN-LABEL; TRANSIENT-STATE KINETICS; ALKALI-METAL SALTS; ROTATIONAL-DYNAMICS; CAGED-ATP; STRUCTURAL-CHANGES; REACTION-MECHANISM AB We have used time-resolved electron paramagnetic resonance (EPR) and quenched-flow kinetics in order to investigate the dynamics of Ca-ATPase conformational changes involved in Ca2+ pumping in sarcoplasmic reticulum (SR) membranes at 2 degrees C. The Ca-ATPase was selectively labeled with an iodoacetamide spin label (IASL), which yields EPR spectra sensitive to enzyme conformational changes during ATP-induced enzymatic cycling. The addition of ATP, AMPPCP, CrATP, or ADP decreased the rotational mobility of a fraction of the probes, indicating a distinct protein conformational state corresponding to this probe population, while P-i under conditions producing ''backdoor'' phosphorylation produced no spectral change. Transient changes in the amplitude of the restricted component associated with the pre-steady state of Ca2+ pumping were detected with 10 ms time resolution after an [ATP] jump produced by laser flash photolysis of caged ATP in the EPR sample. The laser energy was adjusted to generate 100 mu M ATP from 1 mM caged ATP. At 0.1 M KCl, the EPR transient consisted of a brief initial lag phase, a monoexponential phase with a rate of 20 s(-1), and a decay back to the initial intensity after the ATP had been consumed. Raising [KCl] from 0.1 to 0.4 M slowed the rate of the exponential phase from 20 to 6 s(-1). Lowering the pH from 7 to 6, which increased the rate of caged ATP photolysis, eliminated the lag but did not change the apparent rate of the EPR signal rise. Parallel acid quenched-flow experiments conducted at 0.1 M KCl and 100 mu M ATP produced fast (50-58 s(-1)) and slow (20 s(-1)) phases of phosphoenzyme formation. Increasing [KCl] from 0.1 to 0.4 M decreased the rate of the slow phase of phosphorylation from 20 to 5 s(-1), without affecting the fast phase. The close correlation between the slow phase of phosphorylation and the exponential phase of the EPR signal suggests that the spin probe monitors a conformational event associated with phosphoenzyme formation in a population of catalytic sites with delayed kinetics. We propose that this constraint is imposed by conformational coupling between the catalytic subunits in a Ca-ATPase oligomer and that, consequently, the EPR signal reflects changes in quaternary protein structure as well as changes in secondary and tertiary structure associated with ATP-dependent phosphorylation. C1 UNIV MINNESOTA,SCH MED,DEPT BIOCHEM,MINNEAPOLIS,MN 55455. NIA,BALTIMORE CITY HOSP,CTR GERONTOL RES,BALTIMORE,MD 21224. RI Thomas, David/B-4257-2012 FU NIAMS NIH HHS [AR39754]; NIGMS NIH HHS [GM27906] NR 94 TC 29 Z9 29 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 11 PY 1995 VL 34 IS 14 BP 4864 EP 4879 DI 10.1021/bi00014a044 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT032 UT WOS:A1995QT03200044 PM 7718593 ER PT J AU LECCHI, P LE, HMT PANNELL, LK AF LECCHI, P LE, HMT PANNELL, LK TI 6-AZA-A-THIOTHYMINE - A MATRIX FOR MALDI SPECTRA OF OLIGONUCLEOTIDES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID LASER-DESORPTION IONIZATION; MASS-SPECTROMETRY; PROTEINS RP LECCHI, P (reprint author), NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892, USA. NR 9 TC 67 Z9 67 U1 1 U2 5 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 APR 11 PY 1995 VL 23 IS 7 BP 1276 EP 1277 DI 10.1093/nar/23.7.1276 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QW317 UT WOS:A1995QW31700029 PM 7739909 ER PT J AU JUNGWIRTH, C REBBERT, M OZATO, K DEGEN, HJ SCHULZ, U DAWID, IB AF JUNGWIRTH, C REBBERT, M OZATO, K DEGEN, HJ SCHULZ, U DAWID, IB TI CHICKEN INTERFERON CONSENSUS SEQUENCE-BINDING PROTEIN (ICSBP) AND INTERFERON REGULATORY FACTOR (IRF)-1 GENES REVEAL EVOLUTIONARY CONSERVATION IN THE IRF GENE FAMILY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIVIRAL ACTIVITY; DNA-BINDING PROTEIN; EVOLUTION; AVIAN ID TRANSCRIPTION FACTOR; RESPONSIVE ELEMENT; INDUCIBLE GENES; GAMMA; EXPRESSION; DOMAIN; IFN; MYB; MACROPHAGE; INHIBITORS AB Members of the IRF family mediate transcriptional responses to interferons (IFNs) and to virus infection. So far, proteins of this family have been studied only among mammalian species, Here we report the isolation of cDNA clones encoding two members of this family from chicken, interferon consensus sequence-binding protein (ICSBP) and IRF-1. The predicted chicken ICSBP and IRF-1 proteins show high levels of sequence similarity to their corresponding human and mouse counterparts. Sequence identities in the putative DNA-binding domains of chicken and human ICSBP and IRF-1 were 97% and 89%, respectively, whereas the C-terminal regions showed identities of 64% and 51%; sequence relationships with mouse ICSBP and IRF-1 are very similar. Chicken ICSBP was found to be expressed in several embryonic tissues, and both chicken IRF-1 and ICSBP were strongly induced in chicken fibroblasts by IFN treatment, supporting the involvement of these factors in IFN regulated gene expression. The presence of proteins homologous to mammalian IRF family members, together with earlier observations on the occurrence of functionally homologous IFN-responsive elements in chicken and mammalian genes, highlights the conservation of transcriptional mechanisms in the IFN system, a finding that contrasts with the extensive sequence and functional divergence of the IFNs. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. UNIV WURZBURG,INST VIROL & IMMUNOBIOL,D-97078 WURZBURG,GERMANY. UNIV FREIBURG,DEPT VIROL,D-79009 FREIBURG,GERMANY. RP JUNGWIRTH, C (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 37 TC 32 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3105 EP 3109 DI 10.1073/pnas.92.8.3105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800007 PM 7536924 ER PT J AU RICHARDSON, JH SODROSKI, JG WALDMANN, TA MARASCO, WA AF RICHARDSON, JH SODROSKI, JG WALDMANN, TA MARASCO, WA TI PHENOTYPIC KNOCKOUT OF THE HIGH-AFFINITY HUMAN INTERLEUKIN-2 RECEPTOR BY INTRACELLULAR SINGLE-CHAIN ANTIBODIES AGAINST THE ALPHA-SUBUNIT OF THE RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTI-TAC; ADULT T-CELL LEUKEMIA; GENE THERAPY ID T-CELL GROWTH; MONOCLONAL-ANTIBODY; IL-2 RECEPTOR; TAC ANTIGEN; EXPRESSION; PROTEINS; COMPLEX; TARGET; GENES AB The experimental manipulation of peptide growth hormones and their cellular receptors is central to understanding the pathways governing cellular signaling and growth control. Previous work has shown that intracellular antibodies targeted to the endoplasmic reticulum (ER) can be used to capture specific proteins as they enter the ER, preventing their transport to the cell surface. Here we have used this technology to inhibit the cell surface expression of the alpha subunit of the high-affinity interleukin 2 receptor (IL-2R alpha). A single chain variable-region fragment of the anti-Tac monoclonal antibody was constructed with a signal peptide and a C-terminal ER retention signal. Intracellular expression of the single-chain antibody was found to completely abrogate cell surface expression of IL-2R alpha in stimulated Jurkat T cells, IL-2R alpha was detectable within the Jurkat cells as an immature 40-kDa form that was sensitive to endoglycosidase H, consistent with its retention in a pre- or early Golgi compartment. A single-chain antibody lacking the ER retention signal was also able to inhibit cell surface expression of IL-2R alpha although the mechanism appeared to involve rapid degradation of the receptor chain within the ER. These intracellular antibodies will provide a valuable tool for examining the role of IL-2R alpha in T-cell activation, IL-2 signal transduction, and the deregulated growth of leukemic cells which overexpress IL-2R alpha. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. NCI,METAB BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [AI28785, P30 AI28691] NR 36 TC 88 Z9 89 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3137 EP 3141 DI 10.1073/pnas.92.8.3137 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800014 PM 7724529 ER PT J AU LEHNHERR, H YARMOLINSKY, MB AF LEHNHERR, H YARMOLINSKY, MB TI ADDICTION PROTEIN PHD OF PLASMID PROPHAGE P1 IS A SUBSTRATE OF THE CLPXP SERINE-PROTEASE OF ESCHERICHIA-COLI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BACTERIOPHAGE-P1; PLASMID STABILITY; POST-SEGREGATIONAL KILLING; ATP-DEPENDENT PROTEASE; HOMEOSTASIS ID ATP-DEPENDENT PROTEASE; STABLE MAINTENANCE; REGULATORY SUBUNIT; PROTEOLYSIS; SEQUENCE; SYSTEM; GENE; IDENTIFICATION; DEGRADATION; EXPRESSION AB Plasmid-encoded addiction genes augment the apparent stability of various low copy number bacterial plasmids by selectively killing plasmid-free (cured) segregants or their progeny. The addiction module of plasmid prophage P1 consists of a pair of genes called phd and doc. Phd serves to prevent host death when the prophage is retained and, should retention mechanisms fail, Doc causes death on curing. Doc acts as a cell toxin to which Phd is an antidote. In this study we show that host mutants with defects in either subunit of the ClpXP protease survive the loss of a plasmid that contains a P1 addiction module. The small antidote protein Phd is fully stable in these two mutant hosts, whereas it is labile in a wild-type host. We conclude that the role of ClpXP in the addiction mechanism of P1 is to degrade the Phd protein. This conclusion situates P1 among plasmids that elicit severe withdrawal symptoms and are able to do so because they encode both a cell toxin and an actively degraded macromolecule that blocks the synthesis or function of the toxin. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 32 TC 140 Z9 142 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3274 EP 3277 DI 10.1073/pnas.92.8.3274 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800042 PM 7724551 ER PT J AU FUKASAWA, K VANDEWOUDE, GF AF FUKASAWA, K VANDEWOUDE, GF TI MOS OVEREXPRESSION IN SWISS 3T3 CELLS INDUCES MEIOTIC-LIKE ALTERATIONS OF THE MITOTIC SPINDLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID XENOPUS-OOCYTES; MAP KINASE; SACCHAROMYCES-CEREVISIAE; ASTRAL MICROTUBULES; PROTO-ONCOGENE; MATURATION; PRODUCT; CYCLE; METAPHASE; HOMOLOG AB High levels of mos protooncogene product are expressed during oocyte meiotic maturation and Mos has been implicated in formation of the spindle and spindle pole. Here, we show that in Swiss 3T3 cells with 4N DNA content, high levels of Mos lead to the production of binucleated cells. The Swiss 3T3 cells in mitosis, before binucleation occurs, are anastral and the spindle poles are juxtaposed to the cell membrane. These phenotypes may be related to the meiotic process of attachment of the spindle pole to the oocyte membrane during polar body formation. The production of binucleated somatic cells could result from attachment of the altered mitotic spindle pole to the cell membrane that interferes with cytokinesis but not karyokinesis. This can explain at least one form of genetic instability that leads to altered DNA content in tumor cells. C1 NCI, FREDERICK CANC RES & DEV CTR, ADV BIOSCI LABS, BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-46000] NR 40 TC 25 Z9 25 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3430 EP 3434 DI 10.1073/pnas.92.8.3430 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800074 PM 7724579 ER PT J AU COOK, JC CHOCK, PB AF COOK, JC CHOCK, PB TI PHOSPHORYLATION OF UBIQUITIN-ACTIVATING ENZYME IN CULTURED-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-DEGRADATION; CONJUGATING ENZYMES; MECHANISM; INVITRO; SYSTEM AB Ubiquitin-activating enzyme, E1, is the first enzyme in the pathway leading: to formation of ubiquitin-protein conjugates. E1 exists as two isoforms in human cells which are separable by electrophoresis. These isoforms migrate with apparent molecular sizes of 110 kDa and 117 kDa in SDS/polyacrylamide gels. Immunoprecipitiation of E1 from lysates of HeLa cells metabolically labeled with [P-32]phosphate indicated the presence of a phosphorylated form of E1 which migrates at 117 kDa. Phospho amino acid analysis identified serine as the phosphorylated residue in E1. Phosphorylated E1 was also detected in normal and transformed cells from another human cell line. Phosphatase-catalyzed dephosphorylation of E1 in vitro did not eliminate the 117-kDa E1 isoform detected by Coomassie staining after SDS/polyacrylamide gel electrophoresis, thereby demonstrating that phosphorylation is not the sole structural feature differentiating the isoforms of E1. These observations suggest new hypotheses concerning mechanisms of metabolic regulation of the ubiquitin conjugation pathway. C1 NHLBI,BIOCHEM LAB,METAB REGULAT SECT,BETHESDA,MD 20892. NR 26 TC 16 Z9 16 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3454 EP 3457 DI 10.1073/pnas.92.8.3454 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800079 PM 7724583 ER PT J AU DROLET, M PHOENIX, P MENZEL, R MASSE, E LIU, LF CROUCH, RJ AF DROLET, M PHOENIX, P MENZEL, R MASSE, E LIU, LF CROUCH, RJ TI OVEREXPRESSION OF RNASE-H PARTIALLY COMPLEMENTS THE GROWTH DEFECT OF AN ESCHERICHIA-COLI DELTA-TOPA MUTANT - R-LOOP FORMATION IS A MAJOR PROBLEM IN THE ABSENCE OF DNA TOPOISOMERASE-I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GYRASE GENES; MUTATIONS; TRANSCRIPTION; RNH; RECOMBINATION; REPLICATION; TEMPLATE; INVIVO AB Previous biochemical studies have suggested a role for bacterial DNA topoisomerase (TOPO) I in the suppression of R-loop formation during transcription, In this report, we present several pieces of genetic evidence to support a model in which R-loop formation is dynamically regulated during transcription by activities of multiple DNA TOPOs and RNase H. In addition, our results suggest that events leading to the serious growth problems in the absence of DNA TOPO I are linked to R-loop formation. We show that the overexpression of RNase H, an enzyme that degrades the RNA moiety of an R loop, can partially compensate for the absence of DNA TOPO I. We also note that a defect in DNA gyrase can correct several phenotypes associated with a mutation in the rnhA gene, which encodes the major RNase H activity. In addition, we found that a combination of topA and rnhA mutations is lethal. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. RP DROLET, M (reprint author), UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,CP 6128 SUCCURSALE CTR VILLE,MONTREAL,PQ H3C 3J7,CANADA. NR 31 TC 127 Z9 128 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3526 EP 3530 DI 10.1073/pnas.92.8.3526 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800094 PM 7536935 ER PT J AU MA, YC KIM, HY AF MA, YC KIM, HY TI DEVELOPMENT OF THE ONLINE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY THERMOSPRAY MASS-SPECTROMETRY METHOD FOR THE ANALYSIS OF PHOSPHOLIPID MOLECULAR-SPECIES IN RAT-BRAIN SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID INOSITOL LIPIDS; RECOGNITION; MECHANISMS; RETINA AB An on-line thermospray liquid chromatography/mass spectrometry method was developed to rapidly analyze phosphoglyceride molecular species in biological fluid. After total lipid extraction, the extract was subjected to the analysis using on-line reversed-phase high-performance liquid chromatography (HPLC) and filament-on thermospray mass spectrometry. Using nonconventional HPLC conditions, partial separation of individual phospholipid class (phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine) and partial separation of molecular species within each class were achieved. In addition, good peak shape was maintained throughout the analysis. By monitoring characteristic fragment ions (diacylglycerol ions) formed in the filament-on thermospray process and according to the retention time, individual molecular species in each phospholipid class can be identified. Using this method, we observed significant differences in the molecular species composition of each phospholipid class in rat whole-brain lipid. Although nonlinear calibration curves were observed for all the diacylglycerol ions monitored, even in the presence of internal standard, semiquantitative and quantitative results still could be obtained for a mixture of phospholipids. (C) 1995 Academic Press, Inc. C1 NIAAA, LMBB, MASS SPECTROMETRY SECT, BETHESDA, MD 20892 USA. NR 29 TC 47 Z9 48 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 10 PY 1995 VL 226 IS 2 BP 293 EP 301 DI 10.1006/abio.1995.1228 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QR536 UT WOS:A1995QR53600016 PM 7793631 ER PT J AU NIETO, FJ ALONSO, J CHAMBLESS, LE ZHONG, M CERASO, M ROMM, FJ COOPER, L FOLSOM, AR SZKLO, M AF NIETO, FJ ALONSO, J CHAMBLESS, LE ZHONG, M CERASO, M ROMM, FJ COOPER, L FOLSOM, AR SZKLO, M TI POPULATION AWARENESS AND CONTROL OF HYPERTENSION AND HYPERCHOLESTEROLEMIA - THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MINNESOTA HEART SURVEY; CITY MINORITY POPULATION; SERUM TOTAL CHOLESTEROL; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; 2 NATIONAL SURVEYS; CARDIOVASCULAR-DISEASE; ANTIHYPERTENSIVE TREATMENT; STROKE MORTALITY; PREVALENCE AB Background: A national program for hypertension detection and control was implemented in the 1970s, whereas a similar program for control of hypercholesterolemia has been implemented in recent years. We studied the levels of awareness, treatment, and control of these conditions in US population samples during a 3-year period (1987 to 1989). Methods: The levels of awareness, treatment (by medication), and adequate control of hypertension (systolic blood pressure, greater than or equal to 140 mm Hg; diastolic blood pressure, greater than or equal to 90 mm Hg; or antihypertensive medication) and hypercholesterolemia (serum cholesterol level, greater than or equal to 6.21 mmol/L [greater than or equal to 240 mg/dL], or lipid-lowering medication) were studied among participants in the baseline examination of the Atherosclerosis Risk in Communities Study, including 15 739 individuals aged 45 to 64 years. Results: Eighty-four percent of the hypertensive subjects and 42% of the hypercholesterolemic subjects were aware of their conditions. Overall, 50% of the hypertensive subjects and only 4% of the hypercholesterolemic subjects had their conditions both treated and controlled. Rates of hypertension prevalence, awareness, and control remained stable during the 3-year study period. Hypercholesterolemia prevalence decreased from 30% in 1987 to 25% in 1989; its awareness increased from 31% to 50% during the same period. Hypertensive women were more likely than hypertensive men to be aware and treated, whereas hypercholesterolemia awareness was higher in men than in women. Hypertension awareness was highest in black women, but black hypertensive subjects were less likely than whites to be treated and to have their hypertension controlled. Black hypercholesterolemic subjects were less likely to be either aware or treated. Conclusions: After the recent implementation of the National Cholesterol Education Program, the levels of awareness, treatment, and control of hypercholesterolemia are improving at a high rate, although they are still substantially lower than those for hypertension. Further improvement is necessary, particularly among certain population groups, such as blacks. C1 UNIV AUTONOMA BARCELONA, INST MUNICIPAL INVEST MED, E-08193 BARCELONA, SPAIN. UNIV N CAROLINA, DEPT BIOSTAT, CHAPEL HILL, NC USA. MARYLAND MED SOC, BALTIMORE, MD USA. BOWMAN GRAY SCH MED, DEPT FAMILY & COMMUNITY MED, WINSTON SALEM, NC USA. NHLBI, BETHESDA, MD 20892 USA. UNIV MINNESOTA, DEPT EPIDEMIOL, MINNEAPOLIS, MN 55455 USA. RP NIETO, FJ (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. RI yu, yan/C-2322-2012; Alonso, Jordi/A-5514-2010 OI Alonso, Jordi/0000-0001-8627-9636 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 42 TC 133 Z9 134 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 1995 VL 155 IS 7 BP 677 EP 684 DI 10.1001/archinte.155.7.677 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA QQ380 UT WOS:A1995QQ38000003 PM 7695455 ER PT J AU GOLDBERG, RJ BURCHFIEL, CM BENFANTE, R CHIU, D REED, DM YANO, K AF GOLDBERG, RJ BURCHFIEL, CM BENFANTE, R CHIU, D REED, DM YANO, K TI LIFE-STYLE AND BIOLOGIC FACTORS ASSOCIATED WITH ATHEROSCLEROTIC DISEASE IN MIDDLE-AGED MEN - 20-YEAR FINDINGS FROM THE HONOLULU HEART PROGRAM SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID JAPANESE MEN; RISK-FACTORS; CARDIOVASCULAR-DISEASE; 10-YEAR INCIDENCE; FOLLOW-UP; CORONARY; MORTALITY; STROKE; HAWAII; ASCERTAINMENT AB Objectives: To examine the association between a variety of baseline lifestyle and biologic factors in a middle-aged cohort of Japanese-American men and the 20-year incidence rates of total atherosclerotic end points and each of the initial clinical manifestations of this disease, including fatal and nonfatal coronary heart disease, angina pectoris, thromboembolic strokes, and aortic aneurysms. Design: Prospective epidemiologic study. Population:Japanese-American men (N=2710) between the ages of SS and 64 years at the time of the initial clinical examination of the Honolulu Heart Program (1965 through 1968) free from evidence of coronary heart disease, cerebrovascular disease, cancer, or aortic aneurysms. Results: Among the men studied, 602 atherosclerotic events developed during the 23-year period of follow-up (1965 through 1988). After adjustment for each of the baseline characteristics examined, significant positive associations between quartile cutoffs of body mass index, systolic blood pressure, serum levels of cholesterol, triglycerides, glucose, and uric acid, as well as cigarette smoking, and the occurrence of any atherosclerotic end point were seen, while an inverse association with alcohol. consumption was observed. Characteristics associated with the development of other fatal and nonfatal clinical events in this cohort, including coronary heart disease, thromboembolic stroke, and aortic aneurysms are presented with accompanying relative and attributable risks. Conclusions: The results of this prospective epidemiologic study provide insights to the long-term predictive utility of the commonly accepted risk factors for coronary heart disease in relation to the different clinical manifestations of atherosclerosis in a middle-aged male cohort followed up for approximately 20 years. These results provide additional support for risk factor modification in middle-aged men and for the encouragement of positive long-term lifestyle changes, C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI 96817. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,EPIDEMIOL RES SECT,HONOLULU,HI. BUCK CTR RES AGING,NOVATO,CA. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NR 46 TC 65 Z9 68 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD APR 10 PY 1995 VL 155 IS 7 BP 686 EP 694 DI 10.1001/archinte.155.7.686 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA QQ380 UT WOS:A1995QQ38000004 PM 7695456 ER PT J AU IRIBARREN, C REED, DM WERGOWSKE, G BURCHFIEL, CM DWYER, JH AF IRIBARREN, C REED, DM WERGOWSKE, G BURCHFIEL, CM DWYER, JH TI SERUM-CHOLESTEROL LEVEL AND MORTALITY DUE TO SUICIDE AND TRAUMA IN THE HONOLULU HEART PROGRAM SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PLASMA-CHOLESTEROL; ALCOHOL-ABUSE; MEN; RISK; BEHAVIOR; CORONARY; DEATH; POPULATION; DEPRESSION; SEROTONIN AB Background: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. Methods: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. Results: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P=.02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk=0.89; 95% confidence interval, 0.70 to 1.13; P=.44). Heavy alcohol consumption (>1200 mt of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk=1.86; 95% confidence interval, 1.07 to 3.22; P=.02). Conclusions: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events. C1 UNIV SO CALIF, SCH MED, INST PREVENT RES, LOS ANGELES, CA 90033 USA. UNIV SO CALIF, SCH MED, ATHEROSCLEROSIS RES INST, DEPT MED, LOS ANGELES, CA 90033 USA. BUCK CTR RES AGING, NOVATO, CA USA. KUAKINI MED CTR, HONOLULU HEART PROGRAM, HONOLULU, HI USA. NHLBI, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HO1-HC-02901, N01-HV-02901] NR 38 TC 51 Z9 52 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 1995 VL 155 IS 7 BP 695 EP 700 DI 10.1001/archinte.155.7.695 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QQ380 UT WOS:A1995QQ38000005 PM 7695457 ER PT J AU BAR, I DEROUVROIT, CL ROYAUX, I KRIZMAN, DB DERNONCOURT, C RUELLE, D BECKERS, MC GOFFINET, AM AF BAR, I DEROUVROIT, CL ROYAUX, I KRIZMAN, DB DERNONCOURT, C RUELLE, D BECKERS, MC GOFFINET, AM TI A YAC CONTIG CONTAINING THE REELER LOCUS WITH PRELIMINARY CHARACTERIZATION OF CANDIDATE GENE FRAGMENTS SO GENOMICS LA English DT Article ID SEQUENCES; DNA; SELECTION; REGIONS; MICE AB The reeler mutation in the mouse maps to proximal chromosome 5 and defines a key gene involved in brain development and evolution. No gene product is known, and the locus is currently being characterized by positional cloning, YAC clones corresponding to the closest markers D5Mit61 and D5Mit72 have been isolated. Cloned extremities of the YAC inserts were used to construct a 1.1-Mb contig, a 700-kb fragment of which was shown to contain the reeler locus. The integrity of the contig was verified by physical mapping on genomic DNA. The classical allele of the reeler mutation was associated with a 150-kb deletion between D5Mit61 and D5Mit72, while no gross chromosomal anomaly was found in the Orleans allele. Candidate coding sequences were isolated to construct a preliminary transcriptional map of the reeler region. Cosmid clones mapping within the rl deletion revealed a large transcript of more than 11 kb, which was present in normal embryonic brain but barely detectable in homozygous rl(Orl)/rl(Orl) embryonic brain, suggesting strongly that it corresponds to the reeler transcript. (C) 1995 Academic Press, Inc. C1 FAC UNIV NOTRE DAME PAIX,SCH MED,DEPT PHYSIOL,B-5000 NAMUR,BELGIUM. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 30 TC 60 Z9 60 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 543 EP 549 DI 10.1016/0888-7543(95)80173-J PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800014 PM 7607678 ER PT J AU GRIGORIOU, M KASTRINAKI, MC MODI, WS THEODORAKIS, K MANKOO, B PACHNIS, V KARAGOGEOS, D AF GRIGORIOU, M KASTRINAKI, MC MODI, WS THEODORAKIS, K MANKOO, B PACHNIS, V KARAGOGEOS, D TI ISOLATION OF THE HUMAN MOX2 HOMEOBOX GENE AND LOCALIZATION TO CHROMOSOME 7P22.1-P21.3 SO GENOMICS LA English DT Article ID GREIG SYNDROME; CRANIOSYNOSTOSIS; FAMILY; MUTATION; SEQUENCE; LINKAGE; DEFINE AB We have isolated and characterized cDNA clones encoding a novel human homeobox gene, MOX2, the homologue of the murine mox-2 gene. The MOX2 protein contains all of the characteristic features of Mox-2 proteins of other vertebrate species, namely the homeobox, the polyhistidine stretch, and a number of potential serine/threonine phosphorylation sites. The homeodomain of MOX2 protein is identical to all other vertebrate species reported so far (rodents and amphibians). Outside the homeodomain, Mox-2 proteins share a high degree of identity, except for a few amino acid differences encountered between the human and the rodent polypeptides. A polyhistidine stretch of 12 amino acids in the N terminal region of the protein is also conserved among humans, rodents, and (only partly) amphibians. The chromosomal position of 7p22.1-p21.3. (C) 1995 Academic Press, Inc. C1 FDN RES & TECHNOL HELLAS, INST MOLEC BIOL & BIOTECHNOL, GR-71110 IRAKLION, GREECE. UNIV CRETE, DEPT BIOL, GR-71110 IRAKLION, GREECE. FREDERICK CANC RES & DEV CTR, BCDP DYNCORP PROGRAM RESOURCES INC, FREDERICK, MD USA. NATL INST MED RES, MRC, GENE STRUCT & EXPRESS LAB, LONDON NW7 1AA, ENGLAND. UNIV CRETE, SCH MED, DEPT BASIC SCI, GR-71110 IRAKLION, GREECE. NR 31 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 550 EP 555 DI 10.1016/0888-7543(95)80174-K PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800015 PM 7607679 ER PT J AU XU, WM KOZAK, CA DESNICK, RJ AF XU, WM KOZAK, CA DESNICK, RJ TI UROPORPHYRINOGEN-III SYNTHASE - MOLECULAR-CLONING, NUCLEOTIDE-SEQUENCE, EXPRESSION OF A MOUSE FULL-LENGTH CDNA, AND ITS LOCALIZATION ON MOUSE CHROMOSOME-7 SO GENOMICS LA English DT Article ID CONGENITAL ERYTHROPOIETIC PORPHYRIA; AMINOTRANSFERASE GENE-SEQUENCES; HUMAN-ERYTHROCYTES; BIOSYNTHESIS; MACROCYCLES; SUBSTRATE; MUTATIONS; RECEPTOR; PROOF; DNA AB Uroporphyrinogen-III synthase (URO-S; EC 4.2.1.75), the fourth enzyme in the heme biosynthetic pathway, is responsible for the conversion of hydroxymethylbilane to the cyclic tetrapyrrole, uroporphyrinogen III. The deficient activity of URO-S is the enzymatic defect in congenital erythropoietic porphyria (CEP), an autosomal recessive disorder. For the generation of a mouse model of CEP, the human URO-S cDNA was used to screen 2 X 10(6) recombinants from a mouse adult liver cDNA library. Ten positive clones were isolated, and dideoxy sequencing of the entire 1.6-kb insert of clone pmUROS-1 revealed 5' and 3' untranslated sequences of 144 and 623 bp, respectively, and an open reading frame of 798 bp encoding a 265-amino-acid polypeptide with a predicted molecular mass of 28,501 Da. The mouse and human coding sequences had 80.5 and 77.8% nucleotide and amino acid identity, respectively. The authenticity of the mouse cDNA was established by expression of the active monomeric enzyme in Escherichia coli. In addition, the analysis of two multilocus genetic crosses localized the mouse gene on chromosome 7, consistent with the mapping of the human gene to a position of conserved synteny on chromosome 10. The isolation, expression, and chromosomal mapping of this full-length cDNA should facilitate studies of the structure and organization of the mouse genomic sequence and the development of a mouse model of CEP for characterization of the disease pathogenesis and evaluation of gene therapy. (C) 1995 Academic Press, Inc. C1 CUNY MT SINAI SCH MED,DEPT HUMAN GENET,NEW YORK,NY 10029. NIAID,BETHESDA,MD 20892. FU NCRR NIH HHS [5 M01 RR00071]; NICHD NIH HHS [5 P30 HD28822]; NIDDK NIH HHS [5 R01 DK26824] NR 38 TC 17 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 556 EP 562 DI 10.1016/0888-7543(95)80175-L PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800016 PM 7607680 ER PT J AU HAJRA, A COLLINS, FS AF HAJRA, A COLLINS, FS TI STRUCTURE OF THE LEUKEMIA-ASSOCIATED HUMAN CBFB GENE SO GENOMICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTORS; MOLECULAR-CLONING; MESSENGER-RNAS; VIRUS ENHANCER; NUCLEAR FACTOR; AML1 GENE; RUNT; SEQUENCES; BINDING AB We have determined the structure of the human CBFB gene, which encodes the beta subunit of the heterodimeric transcription factor core binding factor (CBF). This gene becomes fused to the MYH11 gene encoding smooth muscle myosin heavy chain by an inversion of chromosome 16 that occurs in the M4Eo subtype of acute myeloid leukemia. The CBFB gene contains 6 exons and spans 50 kb. The gene is highly conserved in animal species as distant as Drosophila, and the exon boundaries are in locations identical to those of the murine Cbfb homologue. The CBPB promoter region has typical features of a housekeeping gene, including high G+C content, high frequency of CpG dinucleotides, and lack of canonical TATA and CCAAT boxes. This gene has a single transcriptional start site, 345 nucleotides upstream of the beginning of the coding region. The human and mouse CBFB promoters show conservation of several transcriptional regulatory sequence motifs, including binding sites for Sp1, Ets family members, and Myc, but do not contain any CBF binding sites. The 5' end of the human CBFB gene also contains a highly polymorphic, transcribed CGG repeat that is not present in the murine homologue. (C) 1995 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NR 42 TC 20 Z9 21 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 571 EP 579 DI 10.1016/0888-7543(95)80177-N PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800018 PM 7607682 ER PT J AU PAHL, P BERGER, R HART, I CHAE, HZ RHEE, SG PATTERSON, D AF PAHL, P BERGER, R HART, I CHAE, HZ RHEE, SG PATTERSON, D TI LOCALIZATION OF TDPX1, A HUMAN HOMOLOG OF THE YEAST THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE GENE (TPX), TO CHROMOSOME 13Q12 SO GENOMICS LA English DT Note ID AMYOTROPHIC-LATERAL-SCLEROSIS; ANTIOXIDANTS; METABOLISM; LIBRARY; CLONING; PROTEIN; DAMAGE; STRESS; CLONES AB Reactive oxygen species and free radicals that are produced during normal metabolism can potentially damage cellular macromolecules. Defenses against such damage include a number of antioxidant enzymes that specifically target the removal or dismutation of the reactive agent. We report here the isolation and regional mapping of a human gene, TDPX1, that encodes an enzyme homologous to a yeast thioredoxin-dependent peroxide reductase (thioredoxin peroxidase, TPX). The human TDPX1 coding sequence was determined from the product of a polymerase chain reaction (PCR) amplification of human cDNA. Eased on PCR analysis of DNA from a human/rodent somatic cell hybrid panel, the TDPX1 locus was assigned to chromosome 13. Further localization of the locus to 13q12 was accomplished by fluorescence in situ hybridization analysis, using as a probe DNA from a yeast artificial chromosome (YAC) that contains the TDPX1 gene. It was also determined by PCR analysis of various YACs that the TDPX1 locus is in the region of the dinucleotide repeat markers D13S289 and D13S290. This regional mapping localizes the TDPX1 gene to a genomic region recently shown to contain the breast cancer susceptibility gene BRCA2 and a gene associated with a form of muscular dystrophy. Oxygen radical metabolism has been hypothesized to be important for cancer, muscular dystrophy, and other disorders, so TDPX1 should be considered a candidate gene for these diseases. (C) 1995 Academic Press, Inc. C1 ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM BIOPHYS & GENET,DENVER,CO 80262. UNIV COLORADO,CTR CANC,DENVER,CO 80262. NHLBI,BETHESDA,MD 20892. FU NIA NIH HHS [AG00029]; NICHD NIH HHS [HD07197] NR 33 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 602 EP 606 DI 10.1016/0888-7543(95)80183-M PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800024 PM 7607688 ER PT J AU WIJMENGA, C SPECK, NA DRACOPOLI, NC HOFKER, MH LIU, P COLLINS, FS AF WIJMENGA, C SPECK, NA DRACOPOLI, NC HOFKER, MH LIU, P COLLINS, FS TI IDENTIFICATION OF A NEW MURINE RUNT DOMAIN-CONTAINING GENE, CBFA3, AND LOCALIZATION OF THE HUMAN HOMOLOG, CBFA3, TO CHROMOSOME 1P35-PTER SO GENOMICS LA English DT Note ID ACUTE MYELOID-LEUKEMIA; DROSOPHILA SEGMENTATION GENE; FUSION TRANSCRIPT; BINDING-PROTEIN; RECEPTOR-DELTA; NUCLEAR FACTOR; DNA-BINDING; ENHANCER; CORE; TRANSLOCATION AB Core binding factor (CBF) is a heterodimeric transcription factor composed of two distinct subunits. The monomeric beta subunit is ubiquitously expressed, whereas expression of the three alpha subunits isolated previously seems to be restricted mainly to hematopoietic tissues. To isolate additional alpha genes, degenerate oligonucleotides derived from the runt domain-a region shared by all alpha genes-were used for screening cDNA libraries. A 228-bp fragment was isolated from a mouse thymus cDNA library, which showed 82 and 76% DNA sequence identity to the previously isolated murine alpha genes, Cbfa1 and Cbfa2. This novel alpha gene was named Cbfa3. The corresponding sequence from the human homolog CBFA3 was obtained by cosmid cloning and sequencing of the appropriate restriction fragment. The corresponding regions of mouse Cbfa3 and human CBFA3 show 91% nucleotide identity and 100% protein identity. In situ hybridization and physical mapping of somatic cell hybrids localized CBFA3 to chromosome 1p35-pter. (C) 1995 Academic Press, Inc. C1 NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH. LEIDEN UNIV,MGC,DEPT HUMAN GENET,LEIDEN,NETHERLANDS. RI Liu, Paul/A-7976-2012; Wijmenga, Cisca/D-2173-2009; OI Liu, Paul/0000-0002-6779-025X; Wijmenga, Cisca/0000-0002-5635-1614 NR 31 TC 45 Z9 48 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 611 EP 614 DI 10.1016/0888-7543(95)80185-O PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800026 PM 7607690 ER PT J AU CHANG, MS HSU, RY MCNINCH, J COPELAND, NG JENKINS, NA AF CHANG, MS HSU, RY MCNINCH, J COPELAND, NG JENKINS, NA TI THE GENE FOR MURINE MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (THROMBOPOIETIN, THPO) IS LOCATED ON MOUSE CHROMOSOME-16 SO GENOMICS LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP CHANG, MS (reprint author), AMGEN INC,AMGEN CTR,DEPT DEV BIOL,14-1-B-219,THOUSAND OAKS,CA 91320, USA. FU NCI NIH HHS [N01-CO-74101] NR 5 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 10 PY 1995 VL 26 IS 3 BP 636 EP 637 DI 10.1016/0888-7543(95)80193-P PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QV658 UT WOS:A1995QV65800034 PM 7607698 ER PT J AU REDDEL, RR DESILVA, R DUNCAN, EL ROGAN, EM WHITAKER, NJ ZAHRA, DG KE, Y MCMENAMIN, MG GERWIN, BI HARRIS, CC AF REDDEL, RR DESILVA, R DUNCAN, EL ROGAN, EM WHITAKER, NJ ZAHRA, DG KE, Y MCMENAMIN, MG GERWIN, BI HARRIS, CC TI SV40-INDUCED IMMORTALIZATION AND RAS-TRANSFORMATION OF HUMAN BRONCHIAL EPITHELIAL-CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SV40 T-ANTIGEN; HUMAN UROEPITHELIAL CELLS; RETINOBLASTOMA SUSCEPTIBILITY GENE; HUMAN-DIPLOID FIBROBLASTS; NEOPLASTIC TRANSFORMATION; P53 MUTATIONS; VIRUS; PROTEIN; LINES; TRANSFECTION AB Non-tumorigenic SV40-immortalized human cells may be transformed to tumorigenicity by activated oncogenes, but the molecular genetics of this process are still poorly understood. We describe here 4 SV40-transformed bronchial epithelial (BE) cell lines that became immortalized after a period of crisis, and then transfection of 6 BE lines or sub-lines with an activated c-Ha-ras (EJ-ras) oncogene. pSV(2)neo-transfected cells did not form any tumors in athymic nude mice. Even though each of the EJ-ras-transfected lines was shown to be expressing the mutant ros gene, only one cell line, BEAS-2B, and 2 of its sub-lines were tumorigenic after transfection. We conclude that immortalization is not sufficient for BE cells to be transformed by the EJ-ras oncogene. Thus there ave at least 2 unknown genetic events in this in vitro model of carcinogenesis: escape from crisis (immortalization), and development of ability to cooperate with activated ras in tumorigenic transformation. We found no evidence that either immortalization or ability to complement ros is related to abnormalities of the SV40 T antigens, of p110(RB) Or Of p53. (C) 1995 Wiley-Liss, Inc. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP REDDEL, RR (reprint author), CHILDRENS MED RES INST,LOCKED BAG 23,WENTWORTHVILLE,NSW 2145,AUSTRALIA. OI Reddel, Roger/0000-0002-6302-6107 NR 32 TC 35 Z9 37 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 1995 VL 61 IS 2 BP 199 EP 205 PG 7 WC Oncology SC Oncology GA QQ321 UT WOS:A1995QQ32100009 PM 7705948 ER PT J AU GIAVAZZI, R DIBERARDINO, C GAROFALO, A MOTTA, T GOBBI, A SCANZIANI, E GIUDICI, G GALLI, M MAYO, JG BARBUI, T BIONDI, A RAMBALDI, A AF GIAVAZZI, R DIBERARDINO, C GAROFALO, A MOTTA, T GOBBI, A SCANZIANI, E GIUDICI, G GALLI, M MAYO, JG BARBUI, T BIONDI, A RAMBALDI, A TI ESTABLISHMENT OF HUMAN ACUTE MYELOGENOUS LEUKEMIA LINES SECRETING INTERLEUKIN-1-BETA IN SCID MICE SO INTERNATIONAL JOURNAL OF CANCER LA Rumanian DT Article ID ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; SEVERE COMBINED IMMUNODEFICIENCY; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; AUTOCRINE GROWTH-FACTOR; CLONOGENIC CELLS; GM-CSF; PROLIFERATION; DIFFERENTIATION AB A reproducible in vivo model of human acute myelogeneous leukemia (AML) was established in severe combined immunodeficient (SCID) mice. The AML-CL and AML-PS lines were originated from leukemic blasts purified respectively from the peripheral blood of a 27-year-old woman with previously untreated hyperleukocytotic AML and from the bone marrow of a 61-year-old man during the third leukemic relapse. The 2 lines were maintained and serially transplanted i.p. in SCID mice. AML-PS and AML-CL produced ascitogenous gross tumors after approximately 4 and 6 weeks, respectively, and all mice died within 6-8 weeks. Microscopic evaluation of different organs at autopsy showed massive involvement of bone marrow, liver and spleen, though with differences in the tumor burdens for the 2 lines (AML-CL > AML-PS). Flow cytometric analysis documented the spread of leukemic cells to bone marrow, peuipheral blood and spleen. AML-PS and AML-CL cells show an immunophenotypic profile (CD13(+), CD33(+)) and cytogenetic findings similar to freshly isolated blasts. Interleukin-1 beta (IL-1 beta) gene expression was observed by Northern blot analysis in leukemic cells from AML-CL and AML-PS SCID mice. After 24 hr of culture both lines released IL-1 beta in culture supernatants. High levels of circulating IL-1 beta were secreted in plasma of tumor-bearing mice. This AML-SCID murine model could contribute to an understanding of the mechanisms of AML growth in vivo and the possible role of the autocrine production of IL-1 beta in promoting cell growth. (C) 1995 Wiley-Liss, Inc. C1 OSPED RIUNITI BERGAMO,IST ANAT PATOL,I-24100 BERGAMO,ITALY. UNIV MILAN,OSPED SAN GERARDO,PEDIAT CLIN,MONZA,ITALY. NCI,FREDERICK CANC RES & DEV CTR,DTP,DCT,FREDERICK,MD. UNIV MILAN,IST ANAT PATOL VET & PATOL AVIARE,MILAN,ITALY. OSPED RIUNITI BERGAMO,DIV EMATOL,I-24100 BERGAMO,ITALY. RP GIAVAZZI, R (reprint author), MARIO NEGRI INST PHARMACOL RES,CANC METASTASIS TREATMENT LAB,VIA GAVAZZENI 11,I-24125 BERGAMO,ITALY. NR 27 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 1995 VL 61 IS 2 BP 280 EP 285 DI 10.1002/ijc.2910610223 PG 6 WC Oncology SC Oncology GA QQ321 UT WOS:A1995QQ32100022 PM 7705959 ER PT J AU DOWNING, JR LADANYI, M RAFFELD, M WEISS, LM MORRIS, SW AF DOWNING, JR LADANYI, M RAFFELD, M WEISS, LM MORRIS, SW TI LARGE-CELL ANAPLASTIC LYMPHOMA-SPECIFIC TRANSLOCATION IN HODGKINS-DISEASE SO LANCET LA English DT Letter C1 MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. CITY HOPE NATL MED CTR, DUARTE, CA 91010 USA. RP DOWNING, JR (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT PATHOL, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA-50341, CA-01429, CA-21765] NR 5 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 8 PY 1995 VL 345 IS 8954 BP 918 EP 919 DI 10.1016/S0140-6736(95)90030-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QR067 UT WOS:A1995QR06700029 PM 7755790 ER PT J AU LUCEY, DR SHEARER, GM AF LUCEY, DR SHEARER, GM TI LARGE-CELL ANAPLASTIC LYMPHOMA-SPECIFIC TRANSLOCATION IN HODGKINS-DISEASE SO LANCET LA English DT Letter RP LUCEY, DR (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD APR 8 PY 1995 VL 345 IS 8954 BP 919 EP 920 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QR067 UT WOS:A1995QR06700031 PM 7707822 ER PT J AU ROSENBERG, HF AF ROSENBERG, HF TI RECOMBINANT HUMAN EOSINOPHIL CATIONIC PROTEIN - RIBONUCLEASE-ACTIVITY IS NOT ESSENTIAL FOR CYTOTOXICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SCHISTOSOMA-MANSONI; GRANULE PROTEINS; HYPEREOSINOPHILIC SYNDROME; ENDOMYOCARDIAL DISEASE; COMPARATIVE TOXICITY; TRYPANOSOMA-CRUZI; MOLECULAR-CLONING; ESCHERICHIA-COLI; CATHEPSIN-G; NEUROTOXIN AB Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils that has anti-parasitic, antibacterial, and neurotoxic activities; ECP also has ribonuclease activity and structural homology to other mammalian ribonucleases. To determine the relationship between the ribonuclease activity and cytotoxicity of ECP, a method for producing recombinant ECP (rECP) in a prokaryotic expression system was devised. Periplasmic isolates from induced bacterial transfectants contained enzymatically active rECP; micromolar concentrations of rECP were shown to be toxic for Staphylococcus aureus (strain 502A). In contrast; recombinant eosinophil-derived neurotoxin, with 67% amino acid sequence identity to ECP, had little to no toxicity for S. aureus; these findings are analogous to those obtained with purified, granule-derived ECP and eosinophil-derived neurotoxin. Two single base pair mutations were introduced into the coding sequence of rECP (Lys(38) to Arg and His(128) to Asp) to convert ribonuclease active-site residues into non-functional counterparts. These mutations eliminated the ribonuclease activity of rECP but had no discernible effect on the antibacterial activity of this protein, demonstrating that ribonuclease activity and cytotoxicity are, in this case, independent functions of ECP. RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 147 Z9 156 U1 1 U2 3 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 APR 7 PY 1995 VL 270 IS 14 BP 7876 EP 7881 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600017 PM 7713881 ER PT J AU BANIK, U AHMED, SA MCPHIE, P MILES, EW AF BANIK, U AHMED, SA MCPHIE, P MILES, EW TI SUBUNIT ASSEMBLY IN THE TRYPTOPHAN SYNTHASE ALPHA(2)BETA(2) COMPLEX - STABILIZATION BY PYRIDOXAL-PHOSPHATE ALDIMINE INTERMEDIATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; BETA-SUBUNIT; ALPHA-2-BETA-2 COMPLEX; APO-BETA2 SUBUNIT; ALPHA-SUBUNIT; MECHANISM; BINDING; 5'-PHOSPHATE; FORMS AB This work is aimed at understanding subunit assembly in the tryptophan synthase alpha(2) beta(2) complex and the importance of the internal aldimine between pyridoxal phosphate and lysine 87 of the beta(2) subunit of tryptophan synthase for subunit association. We utilize a mutant form of the beta(2) subunit that is unable to form the internal aldimine because lysine 87 is replaced by threonine (K87T). The K87T alpha(2) beta(2) complex is inactive in reactions catalyzed by the beta(2) subunit but retains activity in the reaction catalyzed by the alpha subunit. We find that dialysis removes pyridoxal phosphate much more rapidly from the K87T beta(2) subunit and alpha(2) beta(2) complex than from the wild type counterparts. Activity measurements, gel filtration, and subunit interchange experiments show that the alpha subunit dissociates more readily from the K87T beta(2) subunit than from the wild type beta(2) subunit. The reaction of L-serine to form an external aldimine with pyridoxal phosphate at the active site of the K87T beta(2) subunit markedly increases the affinity for the alpha subunit and slows removal of pyridoxal phosphate by dialysis. me propose that the external aldimine between L-serine and pyridoxal phosphate bridges the N-domain and the C-domain in the K87T beta(2) subunit. This interdomain bridge may mimic the internal aldimine bond in the wild type beta(2) subunit and stabilize pyridoxal phosphate binding. The interdomain bridges formed by the internal aldimine with the wild type Pa subunit and by the external aldimine with L-serine in the K87T beta(2) subunit may further stabilize interaction with the iv subunit because the alpha/beta interaction site contains residues from both N- and C-domains of the beta(2) subunit. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 40 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 1995 VL 270 IS 14 BP 7944 EP 7949 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600027 PM 7713891 ER PT J AU MIDURA, RJ CALABRO, A YANAGISHITA, M HASCALL, VC AF MIDURA, RJ CALABRO, A YANAGISHITA, M HASCALL, VC TI NONREDUCING END STRUCTURES OF CHONDROITIN SULFATE CHAINS ON AGGRECAN ISOLATED FROM SWARM RAT CHONDROSARCOMA CULTURES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DERMATAN SULFATE; CARTILAGE PROTEOGLYCAN; EMBRYONIC CHICKEN; CORNEAL EXPLANTS; URONIC-ACID; BIOSYNTHESIS; OLIGOSACCHARIDES; CHROMATOGRAPHY AB Chondrocyte cultures derived from the Swarm rat chondrosarcoma were metabolically labeled with [S-35]sulfate or [6-H-3]GlcN. Radiolabeled aggrecan was purified from the cell layer and exhaustively digested with chondroitin ABC lyase. Digestion products were resolved into disaccharide and monosaccharide residues using Toyopearl HW40S chromatography. The separated saccharide pools were reduced with NaBH4 and applied onto a CarboPAC PA1 column to resolve all of the internal disaccharide alditols (unsaturated) from the nonreducing end disaccharide (saturated) and monosaccharide alditols. Mercuric acetate treatment was used prior to carbohydrate analysis to identify unambiguously the saturated from the unsaturated disaccharides. The chondroitin sulfate (CS) chains from these aggrecan preparations contained: (a) an internal disaccharide composition of unsulfated (3-4 per chain), 4-sulfated (similar to 32 per chain), 6-sulfated (similar to 1 per 14 chains), and 4,6-sulfated disaccharides (similar to 1 per 6 chains) and (b) a nonreducing terminal composition of 4-sulfated GalNAc (similar to 4 out of every 7 chains), 4,6-disulfated GalNAc (similar to 2 out of every 7 chains), and GlcUA adjacent to a 4-sulfated GalNAc residue (similar to 1 out of every 7 chains). Thus, the vast majority of these CS chains terminated with a sulfated GalNAc residue. The presence of 4,6-disulfated GalNAc at nonreducing termini is 60-fold more abundant than 4,6-disulfated GalNAc in interior disaccharides. This observation is consistent with the suggestion that disulfation of terminal GalNAc residues is involved in chain termination. C1 UNIV IOWA,DEPT ORTHOPAED SURG,IOWA CITY,IA 52242. NIDR,PROTEOGLYCAN CHEM SECT,BETHESDA,MD 20892. RP MIDURA, RJ (reprint author), CLEVELAND CLIN FDN,DEPT BIOMED ENGN,WB3,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 37 TC 41 Z9 41 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 1995 VL 270 IS 14 BP 8009 EP 8015 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600037 PM 7713901 ER PT J AU GILON, P BIRD, GSJ BIAN, XP YAKEL, JL PUTNEY, JW AF GILON, P BIRD, GSJ BIAN, XP YAKEL, JL PUTNEY, JW TI THE CA2+-MOBILIZING ACTIONS OF A JURKAT CELL EXTRACT ON MAMMALIAN-CELLS XENOPUS-LAEVIS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; INOSITOL TRISPHOSPHATE; INFLUX; THAPSIGARGIN; STORES; CA2+; OSCILLATIONS; INHIBITION; MESSENGER; PROTEIN AB Randriamampita and Tsien (Randriamampita, C., and Tsien, R. Y, (1993) Nature 364, 809-814) suggested that an acid-extracted fraction from a Jurkat cell line contains a messenger responsible for the coupling of calcium entry to the depletion of intracellular stores, i.e. capacitative calcium entry, We found that the extract, prepared as described by Randriamampita and Tsien, caused Ca2+ entry in 1321N1 astrocytoma cells which was not blocked by the D-myo-1,4,5-trisphosphate-receptor antagonist, heparin. In contrast to astrocytoma cells, when applied to mouse lacrimal acinar cells and rat hepatocytes the Jurkat extract always caused the release of intracellular Ca2+, followed by Ca2+ entry across the plasma membrane, This activity of the extract on lacrimal cells was blocked by either intracellular injection of heparin or extracellular atropine, Similarly prepared lacrimal cell extracts gave Ca2+ responses when applied to astrocytoma cells or lacrimal cells which were similar to Obese for Jurkat-derived extract, However, extracts from hepatocytes had no effect, In most Xenopus oocytes, the Jurkat extract had no effect, while in a few oocytes, the extract gave a [Ca2+](i) response similar to that seen in lacrimal cells, that is, release of Ca2+ followed by Ca2+ entry. We conclude that the actions of the Jurkat cell extract are not consistent with its containing the long sought messenger for capacitative calcium entry, It is Likely that this fraction contains a number of factors that mediate Ca2+ response in different cell types, possibly through receptor-mediated mechanisms. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709. NR 19 TC 39 Z9 39 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 APR 7 PY 1995 VL 270 IS 14 BP 8050 EP 8055 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600043 PM 7713906 ER PT J AU KROOG, GS SAINZ, E WORLAND, PJ AKESON, MA BENYA, RV JENSEN, RT BATTEY, JF AF KROOG, GS SAINZ, E WORLAND, PJ AKESON, MA BENYA, RV JENSEN, RT BATTEY, JF TI THE GASTRIN-RELEASING PEPTIDE RECEPTOR IS RAPIDLY PHOSPHORYLATED BY A KINASE OTHER THAN PROTEIN-KINASE-C AFTER EXPOSURE TO AGONIST SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; SWISS 3T3 CELLS; MUSCARINIC CHOLINERGIC RECEPTORS; LIGHT-DEPENDENT PHOSPHORYLATION; PHOTORECEPTOR MEMBRANES; INDUCED DESENSITIZATION; ADENYLATE-CYCLASE; BOMBESIN RECEPTOR; HOMOLOGOUS DESENSITIZATION; BETA-2-ADRENERGIC RECEPTOR AB Several guanine nucleotide-binding protein-coupled receptors are known to be rapidly phosphorylated after agonist exposure. In this study we show that the gastrin-releasing peptide receptor (GRP-R) is rapidly phosphorylated in response to agonist exposure. When [P-32]orthophosphate-labeled cells were exposed to bombesin, the receptor was maximally phosphorylated on serine and threonine residues within 1 min. Although addition of 12-O-tetradecanoylphorbol 13-acetate also resulted in phosphorylation of the GRP-R, elimination of protein kinase C activity using the inhibitor 7-hydroxystaurosporine did not prevent bombesin-induced GRP-R phosphorylation. We conclude that a kinase other than protein kinase C is principally responsible for the rapid, agonist-induced phosphorylation of the GRP-R. C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP KROOG, GS (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BLDG 37,RM 5D02,BETHESDA,MD 20892, USA. NR 53 TC 42 Z9 42 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 APR 7 PY 1995 VL 270 IS 14 BP 8217 EP 8224 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600067 PM 7713928 ER PT J AU BAZAR, L MEIGHEN, D HARRIS, V DUNCAN, R LEVENS, D AVIGAN, M AF BAZAR, L MEIGHEN, D HARRIS, V DUNCAN, R LEVENS, D AVIGAN, M TI TARGETED MELTING AND BINDING OF A DNA REGULATORY ELEMENT BY A TRANSACTIVATOR OF C-MYC SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUPERCOILED PM2 DNA; SINGLE-STRANDED-DNA; MUNG BEAN NUCLEASE; IONIC ENVIRONMENT; TRANSCRIPTION; PROTEIN; CELLS; GENE; SEQUENCES; PROMOTER AB A far upstream element (FUSE) of c-myc stimulates promoter activity when bound by a newly identified trans-acting protein, which is expressed in cycling cells. Since FUSE binding protein (FBP) binds only the noncoding strand (NCS) of its regulatory element in a sequence-specific manner, and not double-stranded (ds) DNA, formation of the protein . DNA complex in vivo first requires unwinding of the DNA helix. In this report, we show evidence that FBP forces strand separation of short stretches of linear dsDNA. Because FUSE is contained within a region of helical instability that is partially unwound in negatively supercoiled DNA, it is a target for more extensive duplex strand separation by FBP, which first exposes and then selectively binds its NCS cognate sequence. In contrast, other single-stranded DNA binding proteins (SSBs) do not demonstrate this FUSE targeting activity. The novel linkage of regional dsDNA melting with cis-element binding by a transcriptional activator has broad implications in the regulation of eukaryotic gene expression. C1 GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,DEPT MED,WASHINGTON,DC 20007. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Levens, David/C-9216-2009; Duncan, Robert/I-8168-2015 OI Levens, David/0000-0002-7616-922X; Duncan, Robert/0000-0001-8409-2501 FU NCI NIH HHS [CA54818] NR 33 TC 52 Z9 52 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 APR 7 PY 1995 VL 270 IS 14 BP 8241 EP 8248 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600070 PM 7713931 ER PT J AU LETOURNEUR, O SECHI, S WILLETTEBROWN, J ROBERTSON, MW KINET, JP AF LETOURNEUR, O SECHI, S WILLETTEBROWN, J ROBERTSON, MW KINET, JP TI GLYCOSYLATION OF HUMAN TRUNCATED FC-EPSILON-RI ALPHA-CHAIN IS NECESSARY FOR EFFICIENT FOLDING IN THE ENDOPLASMIC-RETICULUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY RECEPTOR; EPIDERMAL LANGERHANS CELLS; IMMUNOGLOBULIN-E; IGE RECEPTOR; TRANSFECTED CELLS; SUBUNIT; RAT; EXPRESSION; BINDING; PROTEIN AB The high affinity immunoglobulin E (IgE) receptor is an alpha beta gamma(2) tetrameric complex. The truncated extracellular segment (alpha t) of the heavily glycosylated alpha chain is sufficient for high affinity binding of IgE. Here we have expressed various alpha t mutants in eukaryotic and prokaryotic cells to analyze the role of glycosylation in the folding, stability, and secretion of alpha t. All seven N-linked glycosylation sites in alpha t are glycosylated and their mutations have an additive effect on the folding and secretion of alpha t. Mutation of the seven N-glycosylation sites (Delta 1-7 alpha t) induces misfolding and retention of alpha t in the endoplasmic reticulum. Similarly, tunicamycin treatment reduces substantially the folding efficiency of wild-type alpha t. In contrast, no difference in folding efficiency is detected between wild-type alpha t and Delta 1-7 alpha t expressed in Escherichia coli. In addition, maturation of N-linked oligosaccharides and addition of O-linked carbohydrates are not required for either the transport or the IgE-binding function of alpha t. Furthermore, complete enzymatic deglycosylation does not affect the stability and the IgE-binding capacity of alpha t. Therefore, glycosylation is not intrinsically necessary for proper folding of alpha t but is required for folding in the endoplasmic reticulum. Our data are compatible with the concept that specific interactions between N-linked oligosaccharides and the folding machinery of the endoplasmic reticulum are necessary for efficient folding of alpha t in eukaryotic cells. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. MRC,CTR PROT ENGN,CAMBRIDGE CB2 2QH,ENGLAND. NR 29 TC 88 Z9 91 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 1995 VL 270 IS 14 BP 8249 EP 8256 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600071 PM 7713932 ER PT J AU LI, WQ YU, JC SHIN, DY PIERCE, JH AF LI, WQ YU, JC SHIN, DY PIERCE, JH TI CHARACTERIZATION OF A PROTEIN-KINASE C-DELTA (PKC-DELTA) ATP BINDING MUTANT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOWN-REGULATION; SACCHAROMYCES-CEREVISIAE; SIGNAL TRANSDUCTION; DIFFERENTIATION; ALPHA; ACTIVATION; COMPLEX; CELLS; NPKC; CDNA AB To investigate the function of protein kinase C (PKC)-delta, we mutated its ATP binding site by converting the invariant lysine in the catalytic domain (amino acid 376) to an arginine, Expression vectors containing wild type and mutant PKC-delta cDNAs were generated either with or without an influenza virus hemagglutinin epitope tag. After expression in 32D cells by transfection, the PRC-delta ATP binding mutant (PKC-delta K376R) was not able to phosphorylate itself or the PKC-delta pseudosubstrate region derived substrate, indicating that PKC-delta R376R was an inactive enzyme, PKC activity was inhibited by 67% in 32D cells coexpressing both PKC-delta wild type (PKC-delta WT) and PKC-delta R376R when compared to 32D cells expressing only PKC-delta WT, Mixture of PKC-delta WT and PKC-delta K376R kinase sources in vitro also reduced the enzymatic activity of PKC-delta WT. These results suggest that PKC-delta K376R competes with PRC-delta WT and inhibits PKC-delta WT phosphorylation of its in vitro substrate. While PKC-delta WT overexpressed in 32D cells demonstrated 12-O-tetradecanoylphorbol-13-acetate (TPA)-dependent translocation from the cytosolic to the membrane fraction, PKC-delta K376R was exclusively localized in the membrane fraction even prior to TPA stimulation. Unlike PKC-delta WT which was phosphorylated on tyrosine residue(s) only after TPA treatment, PKC-delta K376R was constitutively phosphorylated on tyrosine residue(s). Although exposure of PKC-delta WT transfectants to TPA induced 32D monocytic differentiation, the 32D/PKC-delta K376R transfectants were resistant to TPA-induced differentiation. Thus, expression of active PRC-delta is required to mediate 32D monocytic differentiation in response to TPA stimulation. C1 NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 22 TC 84 Z9 85 U1 0 U2 4 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 APR 7 PY 1995 VL 270 IS 14 BP 8311 EP 8318 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600078 PM 7713939 ER PT J AU SUPKO, JG PHILLIPS, LR AF SUPKO, JG PHILLIPS, LR TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR GENISTEIN IN BIOLOGICAL-FLUIDS SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID TANDEM MASS-SPECTROMETRY; TYROSINE KINASE-ACTIVITY; SOY PROTEIN PREPARATIONS; CELL-CYCLE PROGRESSION; DNA STRAND BREAKAGE; CANCER CELLS; PHOSPHATIDYLINOSITOL TURNOVER; LEUKEMIA-CELLS; NIH-3T3 CELLS; JAPANESE MEN AB A specific, sensitive and technically convenient HPLC method for assaying genistein in biological fluids has been developed. The compound and 4-hydroxybenzophenone, added as an internal standard, were efficiently isolated from both plasma and urine by extraction with tert.-butyl methyl ether. Following evaporation of the organic solvent, the extract was reconstituted with methanol-0.05 M ammonium acetate buffer, pH 4.7 (30:70, v/v), and loaded onto a 4 mu m Nova-Pak C-8 column (15 cm x 3.9 mm I.D.). Chromatography was performed at ambient temperature using a mobile phase of acetonitrile-0.05 M ammonium formate buffer, pH 4.0 (27:73, v/v), at a flow-rate of 1.0 ml/min, with UV detection at 260 nm. Mean values of the t(R) for the drug and internal standard, determined from chromatograms of the 1 mu g/ml plasma standard during a 6 month period, were 8.27 +/- 0.55 and 11.92 +/- 0.71 min, respectively (S.D., n = 29). With a sample volume of 50 mu l, the lowest concentration of genistein included in the plasma standard curve, 0.020 mu g/ml, was quantified with a 10.7% R.S.D. over a 5 month period. Plasma standards having concentrations of 0.050 to 1.02 mu g/ml exhibited R.S.D. values ranging from 2.3 to 6.1%. The drug was quantified in urine with similar reproducibility. The sensitivity of the assay was adequate for characterizing the plasma pharmacokinetics of genistein in the mouse and dog. However, a 10-fold improvement in sensitivity was afforded by increasing the sample size to 250 mu l, without otherwise modifying the method. Thus, this procedure may prove suitable for determining plasma and urine levels of genistein in humans consuming dietary isoflavonoids in a much more convenient manner than permitted by existing methodology. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,FREDERICK,MD 21701. NR 46 TC 40 Z9 40 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD APR 7 PY 1995 VL 666 IS 1 BP 157 EP 167 DI 10.1016/0378-4347(94)00551-F PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QU357 UT WOS:A1995QU35700017 PM 7655614 ER PT J AU RAUSCHECKER, JP TIAN, B HAUSER, M AF RAUSCHECKER, JP TIAN, B HAUSER, M TI PROCESSING OF COMPLEX SOUNDS IN THE MACAQUE NONPRIMARY AUDITORY-CORTEX SO SCIENCE LA English DT Article ID RHESUS-MONKEY; VISUAL PROPERTIES; SQUIRREL-MONKEY; MACACA-MULATTA; NEURONS; VOCALIZATIONS; ORGANIZATION; RESPONSES; ANATOMY; SPEECH AB Neurons in the superior temporal gyrus of anesthetized rhesus monkeys were exposed to complex acoustic stimuli. Bandpassed noise bursts with defined center frequencies evoked responses that were greatly enhanced over those evoked by pure tons. This finding led to the discovery of at least one new cochleotopic area in the lateral belt of the nonprimary auditory cortex. The best center frequencies of neurons varied along a rostrocaudal axis, and the best bandwidths of the noise bursts varied along a mediolateral axis. When digitized monkey calls were used as stimuli, many neurons showed a preference for some calls over others. Manipulation of the calls' frequency structure and playback of separate components revealed different types of spectral integration. The lateral areas of the monkey auditory cortex appear to be part of a hierarchical sequence in which neurons prefer increasingly complex stimuli and may form an important stage in the preprocessing of communication sounds. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. HARVARD UNIV,DEPT ANTHROPOL,CAMBRIDGE,MA 02138. HARVARD UNIV,DEPT PSYCHOL,PROGRAM NEUROSCI,CAMBRIDGE,MA 02138. RI Rauschecker, Josef/A-4120-2013 NR 35 TC 574 Z9 577 U1 1 U2 10 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 1995 VL 268 IS 5207 BP 111 EP 114 DI 10.1126/science.7701330 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR454 UT WOS:A1995QR45400038 PM 7701330 ER PT J AU FISHER, RJ FIVASH, M AF FISHER, RJ FIVASH, M TI T-CELL RECEPTOR MHC CLASS-I PEPTIDE INTERACTIONS - AFFINITY, KINETICS, AND SPECIFICITY SO SCIENCE LA English DT Article ID LIGAND RP FISHER, RJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. OI Margulies, David/0000-0001-8530-7375 NR 7 TC 0 Z9 0 U1 1 U2 5 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 1995 VL 268 IS 5207 BP 115 EP 117 DI 10.1126/science.7701331 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR454 UT WOS:A1995QR45400040 PM 7701331 ER PT J AU CORR, M SLANETZ, AE BOYD, LF JELONEK, MT KHILKO, S ALRAMADI, BK KIM, YS MAHER, SE BOTHWELL, ALM MARGULIES, DH AF CORR, M SLANETZ, AE BOYD, LF JELONEK, MT KHILKO, S ALRAMADI, BK KIM, YS MAHER, SE BOTHWELL, ALM MARGULIES, DH TI T-CELL RECEPTOR MHC CLASS-I PEPTIDE INTERACTIONS - AFFINITY, KINETICS, AND SPECIFICITY - RESPONSE SO SCIENCE LA English DT Article C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06520. NIAID,BETHESDA,MD 20892. CHUNGNAM NATL UNIV,TAEJON,SOUTH KOREA. RP CORR, M (reprint author), UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093, USA. RI Margulies, David/H-7089-2013 NR 3 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 1995 VL 268 IS 5207 BP 117 EP 117 DI 10.1126/science.268.5207.117 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR454 UT WOS:A1995QR45400041 PM 17755235 ER PT J AU YU, JL NAGARAJAN, S LIU, J YOUNG, N MEDOF, ME AF YU, JL NAGARAJAN, S LIU, J YOUNG, N MEDOF, ME TI CLONING AND CHARACTERIZATION OF THE MOUSE PIG-A GENE SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Note DE PIG-A; GLCNAC-PI; GPI ANCHOR; PNH ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ANCHOR BIOSYNTHESIS; PHOSPHATIDYLINOSITOL; MUTANTS AB Currently there is no experimental animal model for studying paroxysmal nocturnal hemoglobinuria (PNH), an acquired hemolytic anemia linked to mutations of the PIG-A gene. In this study, we cloned and characterized the mouse PIG-A gene. Sequencing of mouse PIG-A cDNA showed that it encodes a 485 amino acid-long protein. Northern hybridizations identified a major mRNA transcript of 3.6 kb and PCR amplifications identified four smaller alternative splice products. Exon:intron junctional analyses of the mouse PIG-A genome showed 6 exons (1(greater than or equal to 60 bp), 2(780 bp), 3(133 bp) 4(133 bp), 5(207 bp), and 6(2276 bp)), the latter 5 of which encompass the coding region. Chromosomal mapping using C57BL/6J X M. Spretus backcross DNA localized the mouse PIG-A gene near the telomeric end of the mouse X chromosome. The isolation of the mouse PIG-A gene opens the possibility for the development of a mouse model of PNH. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NHLBI,HB,BETHESDA,MD 20892. FU NIDDK NIH HHS [P01DK38181]; PHS HHS [M23598] NR 19 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD APR 6 PY 1995 VL 1255 IS 3 BP 344 EP 350 DI 10.1016/0005-2760(95)00015-5 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QT594 UT WOS:A1995QT59400016 PM 7734452 ER PT J AU ERIKSSON, H RIDDERSTRALE, M DEGERMAN, E EKHOLM, D SMITH, CJ MANGANIELLO, VC BELFRAGE, P TORNQVIST, H AF ERIKSSON, H RIDDERSTRALE, M DEGERMAN, E EKHOLM, D SMITH, CJ MANGANIELLO, VC BELFRAGE, P TORNQVIST, H TI EVIDENCE FOR THE KEY ROLE OF THE ADIPOCYTE CGMP-INHIBITED CAMP-PHOSPHODIESTERASE IN THE ANTILIPOLYTIC ACTION OF INSULIN SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE ADIPOCYTE; CAMP-DEPENDENT PROTEIN KINASE; INHIBITOR; INSULIN; LIPOLYSIS; PHOSPHODIESTERASE ID DEPENDENT PROTEIN-KINASE; HORMONE-SENSITIVE LIPASE; CYCLIC-AMP PHOSPHODIESTERASE; RAT ADIPOSE-TISSUE; ISOLATED FAT-CELLS; ADENYLATE-CYCLASE; LIPOLYSIS; PHOSPHORYLATION; ATP; MONOPHOSPHATE AB Enhancement of cAMP degradation by increased cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) activity is thought to be an important component of the mechanism whereby insulin counteracts catecholamine-induced lipolysis in adipocytes. In this study the selective cGI-PDE inhibitor OPC3911 was used to evaluate this role of cGI-PDE activation in intact rat adipocytes with special reference to changes in cAMP levels measured as cAMP-dependent protein kinase (cAMP-PK) activity ratios. OPC3911 completely blocked (IC50 = 0.3 mu M) the maximal inhibitory effect of insulin on noradrenaline-induced lipolysis and the net dephosphorylation of hormone-sensitive lipase and other intracellular target proteins for insulin action, whereas insulin-induced lipogenesis was not changed. The effect of OPC3911 on cAMP-PK activity ratios at different levels of lipolysis achieved by noradrenaline stimulation revealed that the reduction of cAMP-PK caused by 1 nM insulin was completely blocked by 3 mu M OPC3911. The effect of OPC3911 was not due to an excessive increase in cellular cAMP resulting in 'supramaximal' lipolysis unresponsive to insulin. These data demonstrate that reduction in cAMP levels by the activation of cGI-PDE may be sufficient to account for the antilipolytic action of insulin. C1 LUND UNIV,DEPT PAEDIAT,S-22101 LUND,SWEDEN. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RP ERIKSSON, H (reprint author), LUND UNIV,DEPT MED & PHYSIOL CHEM,POB 94,S-22101 LUND,SWEDEN. RI Ridderstrale, Martin/F-7678-2012 NR 46 TC 90 Z9 91 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 6 PY 1995 VL 1266 IS 1 BP 101 EP 107 DI 10.1016/0167-4889(94)00237-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT136 UT WOS:A1995QT13600013 PM 7718614 ER PT J AU BARCHI, JJ RUSS, P JOHNSON, B OTAKA, A NOMIZU, M YAMADA, Y AF BARCHI, JJ RUSS, P JOHNSON, B OTAKA, A NOMIZU, M YAMADA, Y TI GLYCOSYLATION OF THE ACTIVE SEQUENCE SER-ILE-LYS-VAL-ALA-VAL FROM THE ALPHA-1 CHAIN OF LAMININ REDUCES TUMOR-CELL ATTACHMENT ACTIVITY SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID IKVAV SEQUENCE; A-CHAIN; CARBOHYDRATE; OLIGOSACCHARIDES; PEPTIDE AB N-terminal serine O-glycopeptides of SIKVAV-, a sequence located on the long arm of the alpha 1 chain of laminin, were synthesized to study the effect of glycosylation on the adhesive properties of this biologically relevant peptide. The data show that covalently linked carbohydrates decrease the cell-attachment activity in a structurally dependent manner. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP BARCHI, JJ (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014 NR 18 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 6 PY 1995 VL 5 IS 7 BP 711 EP 714 DI 10.1016/0960-894X(95)00100-8 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA QU442 UT WOS:A1995QU44200012 ER PT J AU JACOBSON, JA DANFORTH, DN COWAN, KH DANGELO, T STEINBERG, SM PIERCE, L LIPPMAN, ME LICHTER, AS GLATSTEIN, E OKUNIEFF, P AF JACOBSON, JA DANFORTH, DN COWAN, KH DANGELO, T STEINBERG, SM PIERCE, L LIPPMAN, ME LICHTER, AS GLATSTEIN, E OKUNIEFF, P TI 10-YEAR RESULTS OF A COMPARISON OF CONSERVATION WITH MASTECTOMY IN THE TREATMENT OF STAGE-I AND STAGE-II BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED TRIAL; RADIATION-THERAPY; RECURRENCE; SURGERY; IRRADIATION; LUMPECTOMY; CARCINOMA AB Background. Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer, We update the results of that trial after a median potential follow-up of 10.1 years. Methods. Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy, The 237 patients who actually underwent randomization have been followed for a median of 10.1 years, The primary points were overall survival and disease-free survival. Results. At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P=0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P=0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P=0.17) after recurrences successfully treated by mastectomy were censored from the analysis. Conclusions, In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CANC NURSING SERV,BETHESDA,MD 20892. UNIV MICHIGAN,MED CTR,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. GEORGETOWN UNIV HOSP,LOMBARDI CANC CTR,WASHINGTON,DC 20007. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DEPT RADIAT ONCOL,DALLAS,TX. RP JACOBSON, JA (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT ONCOL BRANCH,BLDG 10,RM B3-B69,BETHESDA,MD 20892, USA. NR 23 TC 532 Z9 543 U1 0 U2 3 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 APR 6 PY 1995 VL 332 IS 14 BP 907 EP 911 DI 10.1056/NEJM199504063321402 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA QP893 UT WOS:A1995QP89300002 PM 7877647 ER PT J AU KARKI, SB DINNOCENZO, JP JONES, JP KORZEKWA, KR AF KARKI, SB DINNOCENZO, JP JONES, JP KORZEKWA, KR TI MECHANISM OF OXIDATIVE AMINE DEALKYLATION OF SUBSTITUTED N,N-DIMETHYLANILINES BY CYTOCHROME-P-450 - APPLICATION OF ISOTOPE EFFECT PROFILES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTRON-TRANSFER REACTIONS; RADICAL-ION-PAIRS; C-C BOND; TRANSFER PHOTOCHEMISTRY; IRON(III) COMPLEXES; CATION RADICALS; NADH MODEL; CYCLOPROPYLAMINES; DEPROTONATION; INACTIVATION AB Isotope effect profiles were determined for the deprotonation of a series of para-substituted N-methyl-N(trideuteriomethyl)aniline cation radicals by pyridine and for hydrogen atom abstraction from the corresponding neutral amines by the tert-butoxyl radical. The profiles model reaction steps in two mechanisms commonly proposed for the oxidative dealkylation of amines by cytochrome P-450. Isotope effect profiles were also determined for the P-450 oxidation of the same set of N,N-bis(dideuteriomethyl)anilines by purified CYP2B1, expressed CYP2B1, phenobarbital-induced microsomal P-450, expressed CYP4B1, expressed CYP1A2, and purified CYP102 (BM3). The profiles for all of the P-450 oxidations were found to be experimentally indistinguishable from the hydrogen atom abstraction profile, and distinctly different from the deprotonation profile. This agreement provides strong evidence that the P-450 oxidatively dealkylates the amines by a hydrogen atom abstraction mechanism. Furthermore, the P-450 isotope effect profiles indicate that the reaction mechanism is conserved in both mammalian and bacterial enzymes. C1 UNIV ROCHESTER,DEPT CHEM,ROCHESTER,NY 14627. UNIV ROCHESTER,DEPT PHARMACOL,ROCHESTER,NY 14627. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 57 TC 122 Z9 124 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 5 PY 1995 VL 117 IS 13 BP 3657 EP 3657 DI 10.1021/ja00118a001 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA QR579 UT WOS:A1995QR57900001 ER PT J AU TAKIMOTO, CH AF TAKIMOTO, CH TI ENIGMA OF FLUOROURACIL AND LEVAMISOLE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SYNTHASE MESSENGER-RNA; COLORECTAL-CARCINOMA; THYMIDYLATE SYNTHASE; ADJUVANT THERAPY; COLON-CARCINOMA; 5-FLUOROURACIL; CANCER; TRANSLATION RP TAKIMOTO, CH (reprint author), NCI,BETHESDA NAVAL HOSP,MED ONCOL BRANCH,BLDG 8,RM 5101,BETHESDA,MD 20889, USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 5 PY 1995 VL 87 IS 7 BP 471 EP 473 DI 10.1093/jnci/87.7.471 PG 3 WC Oncology SC Oncology GA QP450 UT WOS:A1995QP45000001 PM 7707428 ER PT J AU TRAVIS, LB CURTIS, RE GLIMELIUS, B HOLOWAY, EJ VANLEEUWEN, FE LYNCH, CF HAGENBEEK, A STOVALL, M BANKS, PM ADAMI, J GOSPODAROWICZ, MK WACHOLDER, S INSKIP, PD TUCKER, MA BOICE, JD AF TRAVIS, LB CURTIS, RE GLIMELIUS, B HOLOWAY, EJ VANLEEUWEN, FE LYNCH, CF HAGENBEEK, A STOVALL, M BANKS, PM ADAMI, J GOSPODAROWICZ, MK WACHOLDER, S INSKIP, PD TUCKER, MA BOICE, JD TI BLADDER AND KIDNEY CANCER FOLLOWING CYCLOPHOSPHAMIDE THERAPY FOR NON-HODGKINS-LYMPHOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COMBINATION CHEMOTHERAPY; URINARY-BLADDER; 2ND CANCERS; CARCINOMA; VINCRISTINE; PREDNISONE; ADRIAMYCIN; SURVIVORS; MORTALITY; RISK AB Background: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect, The largest analysis to date included only seven cases of bladder cancer, No investigation has estimated the risk of kidney cancer, Purpose: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy, Methods: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy, Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects, Radiation dose to the target organ was estimated from individual radiotherapy records, Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality, Results: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose, Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent, Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004), Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy, Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed, Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer, Conclusions: Cyclophosphamide-related bladder cancer is dose dependent, For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up, At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients, Implications: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points, The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighed against the curative gains provided by cyclophosphamide, Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders. C1 UNIV UPPSALA HOSP,UPPSALA,SWEDEN. ONTARIO CANC TREATMENT & RES FDN,TORONTO,ON,CANADA. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. UNIV IOWA,IOWA CITY,IA. DR DANIEL DEN HOED CANC CTR,3008 AE ROTTERDAM,NETHERLANDS. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. PRINCESS MARGARET HOSP,TORONTO,ON M4X 1K9,CANADA. RP TRAVIS, LB (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 33 TC 193 Z9 194 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 5 PY 1995 VL 87 IS 7 BP 524 EP 530 DI 10.1093/jnci/87.7.524 PG 7 WC Oncology SC Oncology GA QP450 UT WOS:A1995QP45000014 PM 7707439 ER PT J AU LAUFMAN, LR JONES, JJ MORRICE, B HAN, CH HALK, D FISHER, B AF LAUFMAN, LR JONES, JJ MORRICE, B HAN, CH HALK, D FISHER, B TI CASE-REPORT OF A LETHAL CARDIAC TOXIC EFFECT FOLLOWING HIGH-DOSE CYCLOPHOSPHAMIDE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID THERAPY C1 NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. RP LAUFMAN, LR (reprint author), COLUMBUS COMMUNITY CLIN ONCOL PROGRAM,1151 S HIGH ST,COLUMBUS,OH 43206, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 5 PY 1995 VL 87 IS 7 BP 539 EP 540 DI 10.1093/jnci/87.7.539 PG 2 WC Oncology SC Oncology GA QP450 UT WOS:A1995QP45000021 PM 7707444 ER PT J AU LEE, YL HELMAN, L HOFFMAN, T LABORDA, J AF LEE, YL HELMAN, L HOFFMAN, T LABORDA, J TI DLK, PG2 AND PREF-1 MESSENGER-RNAS ENCODE SIMILAR PROTEINS BELONGING TO THE EGF-LIKE SUPERFAMILY - IDENTIFICATION OF POLYMORPHIC VARIANTS OF THIS RNA SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE TRANSMEMBRANE PROTEIN; PROTEIN POLYMORPHISM; EGF-LIKE SUPERFAMILY; CELL DIFFERENTIATION; NEUROENDOCRINE CELL ID NEURAL CREST DERIVATIVES; EPIDERMAL GROWTH-FACTOR; DROSOPHILA-NOTCH; HOMEOTIC GENE; MOUSE HOMOLOG; CELL-LINE; DIFFERENTIATION; SEQUENCE; GLUCOCORTICOIDS; MELANOGASTER AB dlk encodes a transmembrane protein member of the EGF-like family of homeotic proteins, dlk is expressed in the same type of neuroendocrine tissues and tumors as pG2, a gene cloned because of its differential expression in human pheochromocytomas versus neuroblastomas. Human dlk and pG2 cDNAs are around 98% similar in sequence, but the predicted proteins encoded by those genes are apparently unrelated. This fact suggested the existence of polymorphic variants of the same gene. We have sequenced again several pG2 and dlk clones in parallel. We identified a pG2 cDNA species corresponding to an alternatively spliced dlk mRNA, as well as several other variant forms of dlk mRNA. One of the pG2 clones resulted to be identical to human dlk and encode the same EGF-like protein. Pref-1, a cDNA. isolated from 3T3-L1 fibroblasts, encodes a putative protein possessing an extracellular EGF-like domain similar to dlk, but a different intracellular region. Analysis of sequence data from different clones obtained in our laboratory confirmed some of the differences between dlk and Pref-1. However, the putative difference in the intracellular regions of dlk and Pref-1 was due to sequence artifacts. These data suggest that dlk, pG2 and Pref-1 are variant products of the same gene. C1 US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD 20892. RI Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X NR 28 TC 49 Z9 53 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 4 PY 1995 VL 1261 IS 2 BP 223 EP 232 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ952 UT WOS:A1995QQ95200007 PM 7711066 ER PT J AU CVEKI, A MCDERMOTT, JB PIATIGORSKY, J AF CVEKI, A MCDERMOTT, JB PIATIGORSKY, J TI CDNA-ENCODING A CHICKEN PROTEIN (CRP1) WITH HOMOLOGY TO HNRNP TYPE A/B SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Note DE GENE CLONING; RNP PROTEIN FAMILY; (CHICKEN) ID RNA-BINDING PROTEIN; CLONING; FAMILY; DNA; BOX AB The sequence of a cDNA encoding a putative chicken RNA-binding protein is reported. The C-terminal portion of the predicted protein is similar to a family of nucleic acid binding proteins that includes murine CArG box-binding factor CBF-A, human hnRNP A/B, hepatitis B enhancer-binding protein E2BP, and AU-rich RNA-binding protein AUF1. These proteins all have two consecutive RNA recognition motifs. However, the N-terminal 72 amino acids of this deduced chicken protein show no relation to the N-terminal sequences of the other proteins. We call this protein chicken ribonucleoprotein, CRP1. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 12 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 4 PY 1995 VL 1261 IS 2 BP 290 EP 292 DI 10.1016/0167-4781(95)00021-8 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ952 UT WOS:A1995QQ95200017 PM 7711075 ER PT J AU OGUCHI, H PAN, YT KIMURA, S AF OGUCHI, H PAN, YT KIMURA, S TI THE COMPLETE NUCLEOTIDE-SEQUENCE OF THE MOUSE THYROID-SPECIFIC ENHANCER-BINDING PROTEIN (T/EBP) GENE - EXTENSIVE IDENTITY OF THE DEDUCED AMINO-ACID-SEQUENCE WITH THE HUMAN PROTEIN SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Note DE THYROID-SPECIFIC ENHANCER-BINDING PROTEIN (T/EBP); CDNA CLONING; GENE CLONING; GENE STRUCTURE; SEQUENCE COMPARISON ID THYROGLOBULIN PROMOTER; PEROXIDASE GENE; TTF-1; EXPRESSION AB A mouse thyroid-specific enhancer-binding protein (T/EBP) gene and its flanking regions have been cloned and completely sequenced. The gene consists of 2 exons and exhibits high similarity (83-97%) to the rat sequence throughout the coding region and including an intron and up to 1.3 kbp upstream to the ATG initiation codon. A cDNA clone encoding human T/EBP has been also isolated and sequenced. Comparison of the deduced amino acid sequence of T/EBP revealed an extensive identity of 98% between mouse and the human protein. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 15 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 4 PY 1995 VL 1261 IS 2 BP 304 EP 306 DI 10.1016/0167-4781(95)00033-D PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ952 UT WOS:A1995QQ95200021 PM 7711079 ER PT J AU GOLSKI, S OLDS, JL MISHKIN, M OLTON, DS ALKON, DL AF GOLSKI, S OLDS, JL MISHKIN, M OLTON, DS ALKON, DL TI PROTEIN-KINASE-C IN THE HIPPOCAMPUS IS ALTERED BY SPATIAL BUT NOT CUED DISCRIMINATIONS - A COMPONENT TASK-ANALYSIS SO BRAIN RESEARCH LA English DT Article DE HIPPOCAMPUS; PROTEIN KINASE C; SPATIAL DISCRIMINATION; RATS ID PHORBOL ESTER RECEPTOR; PLACE NAVIGATION; CAUDATE-NUCLEUS; SWIMMING POOL; RAT-BRAIN; MEMORY; LESIONS; TRANSLOCATION; LOCALIZATION; PERFORMANCE AB The exact role of the mammalian hippocampus in memory formation remains essentially as an unanswered question for cognitive neuroscience. Experiments with humans and with animals indicate that some types of mnemonic associative processes involve hippocampal function while others do not. Support for the spatial processing hypothesis of hippocampal function has stemmed from the impaired performance of rats with hippocampal lesions in tasks that require spatial discriminations, but not cued discriminations. Previous procedures, however, have confounded the interpretation of spatial versus cued discrimination learning with the number and kinds of irrelevant stimuli present in the discrimination. An empirical set of data describing a role of protein kinase C (PKC) in different mnemonic processes is similarly being developed. Recent work has implicated the activation of this serine-threonine kinase in a variety of learning paradigms, as well as long-term potentiation (LTP), a model system for synaptic plasticity which may subserve some types of learning. The present study employs the principles of component task analysis to examine the role of membrane-associated PKC (mPKC) in hippocampal-dependent memory when all factors other than the type of learning were equivalent. The results indicate that hippocampal mPKC is altered by performance in hippocampally-dependent spatial discriminations, but not hippocampally-independent cued discriminations and provide a general experimental procedure to relate neural changes to specific behavioral changes. C1 JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. NINCDS,ADAPT SYST LAB,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RI Olds, James/D-2867-2011 NR 44 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 3 PY 1995 VL 676 IS 1 BP 53 EP 62 DI 10.1016/0006-8993(95)00080-A PG 10 WC Neurosciences SC Neurosciences & Neurology GA QQ471 UT WOS:A1995QQ47100005 PM 7796178 ER PT J AU TRIESCHMANN, L ALFONSO, PJ CRIPPA, MP WOLFFE, AP BUSTIN, M AF TRIESCHMANN, L ALFONSO, PJ CRIPPA, MP WOLFFE, AP BUSTIN, M TI INCORPORATION OF CHROMOSOMAL-PROTEINS HMG-14/HMG-17 INTO NASCENT NUCLEOSOMES INDUCES AN EXTENDED CHROMATIN CONFORMATION AND ENHANCES THE UTILIZATION OF ACTIVE TRANSCRIPTION COMPLEXES SO EMBO JOURNAL LA English DT Article DE ACTIVE CHROMATIN; CHROMATIN ASSEMBLY; CHROMOSOMAL PROTEINS; TRANSCRIPTION; XENOPUS ID MOBILITY-GROUP PROTEIN-14; CHICKEN ERYTHROCYTE CHROMATIN; RNA POLYMERASE-III; BETA-GLOBIN GENE; REPLICATING DNA; HISTONE TAILS; INVITRO; HMG-17; BINDING; PHOSPHORYLATION AB The role of chromosomal proteins HMG-14 and HMG-17 in the generation of transcriptionally active chromatin was studied in a Xenopus laevis egg extract which supports complementary DNA strand synthesis and chromatin assembly. Chromosomal proteins HMG-14/HMG-17 enhanced transcription from a chromatin template carrying a 5S rRNA gene, but not from a DNA template. The transcriptional potential of chromatin was enhanced only when these proteins were incorporated into the template during, but not after, chromatin assembly. HMG-14 and HMG-17 stimulate transcription by increasing the activity, and not the number, of transcribed templates. They unfold the chromatin template without affecting the nucleosomal repeat or decreasing the content of histone B4. We suggest that HMG-14/HMG-17 enhance transcription by inducing an extended conformation in the chromatin fiber, perhaps due to interactions with histone tails in nucleosomes. By disrupting the higher order chromatin structure HMG-14/HMG-17 increase the accessibility of target sequences to components of the transcriptional apparatus. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RP TRIESCHMANN, L (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. RI crippa, massimo/J-6514-2016; Bustin, Michael/G-6155-2015 OI crippa, massimo/0000-0003-3214-9670; NR 63 TC 72 Z9 74 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 APR 3 PY 1995 VL 14 IS 7 BP 1478 EP 1489 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU574 UT WOS:A1995QU57400021 PM 7729423 ER PT J AU HAYNES, JI GOPALSRIVASTAVA, R FREDERIKSE, PH PIATIGORSKY, J AF HAYNES, JI GOPALSRIVASTAVA, R FREDERIKSE, PH PIATIGORSKY, J TI DIFFERENTIAL USE OF THE REGULATORY ELEMENTS OF THE ALPHA-B-CRYSTALLIN ENHANCER IN CULTURED MURINE LUNG (MLE), LENS (ALPHA-TN4-1) AND MUSCLE (C2C12) CELLS SO GENE LA English DT Article DE RECOMBINANT DNA; TRANSCRIPTION; ENHANCER; TRANSFECTION ID HEAT-SHOCK PROTEIN; EXPRESSION; GENE; IDENTIFICATION; INITIATION; EVOLUTION AB The mouse alpha B-crystallin-encoding gene (alpha B-cry) is highly expressed in the lens and expressed to lesser extents in other tissues. Here, we investigated alpha B-cry expression in mouse-lung-derived MLg cells, Two sizes of MLg alpha B-cry transcripts comigrated with alpha B-cry transcripts contained in total and poly(A)(+)RNA from mouse lung, with preference for the larger species in the MLE cells, Expression of both alpha B-cry promoter/cat reporter gene constructs and alpha B-cry enhancer (nt -427/-259)/herpes simplex virus (HSV) thymidine kinase promoter (ptk)/human growth hormone reporter gene (hGH) constructs was studied in transfected MLg cells and the results compared with those obtained from alpha TN4-1 lens and C2C12 muscle cells, The alpha B-cry enhancer increased activity of the endogenous and tk promoters approx. 2-fold in the MLg cells, in contrast to its 3-7-fold effect in alpha TN4-1 cells and 17-20-fold effect in C2C12 myotubes. Site-specific mutagenesis of the previously identified enhancer control elements, alpha BE-1 (nt -407 to -397), alpha BE-2 (-360 to -327) and MRF (-300 to -288), decreased enhancer strength in transfected MLg cells, DNase I footprinting showed that MLg nuclear proteins occupy only alpha BE-1 and alpha BE-2. Previous data have shown that lens cells use alpha BE-1, alpha BE-2 and alpha BE-3, while muscle cells use: in addition, the muscle regulatory factor-binding site (MRF), Thus, the present experiments correlate tissue-specific enhancer strength and the number of control elements utilized. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 22 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 3 PY 1995 VL 155 IS 2 BP 151 EP 158 DI 10.1016/0378-1119(95)00007-S PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QT085 UT WOS:A1995QT08500001 PM 7536694 ER PT J AU NICHOLS, RC RABEN, N BOERKOEL, CF PLOTZ, PH AF NICHOLS, RC RABEN, N BOERKOEL, CF PLOTZ, PH TI HUMAN ISOLEUCYL-TRANSFER-RNA SYNTHETASE - SEQUENCE OF THE CDNA, ALTERNATIVE MESSENGER-RNA SPLICING, AND THE CHARACTERISTICS OF AN UNUSUALLY LONG C-TERMINAL EXTENSION SO GENE LA English DT Note DE GENE CLONING; POLYMERASE CHAIN REACTION; AUTOANTIGEN; INTERFERON-STIMULATED RESPONSE ELEMENT; REPEAT MOTIF; HIGH-MOLECULAR-WEIGHT COMPLEX ID TRANSFER RNA-SYNTHETASE; AMINOACYL-TRANSFER RNA; COMPLEX; LIVER; AUTOANTIBODIES; RECOGNITION; TRANSLATION; MOTIFS; CELLS; FORMS AB The human isoleucyl-tRNA synthetase (IRS)-encoding cDNA, whose primary structure we report here, has an open reading frame (ORF) which encodes a protein of 1262 amino acids (aa) with strong homology to IRS from yeast (53.5%) and Tetrahymena (51.0%) and contains all the major consensus motifs of class-I hydrophobic amino-acyl-tRNA synthetases (aaRS; MRS, LRS, VRS, IRS), However, the human enzyme has an unusually long C-terminal extension composed, in part, of a twice-repeated motif which shows no homology to any reported protein. We also report the presence of a coiled-coil-like motif in the C-terminal half of the protein. The mRNA has an additional exon in the 5'-untranslated region (UTR) which is alternatively spliced, giving rise to two types of mRNA, both of which are expressed in several human tissues. The longer of the two transcripts contains predicted secondary structure in the 5'-UTR which may reduce the translational efficiency of this mRNA. Two possible regulatory elements in the 5'-UTR, an interferon-stimulated response element (ISRE)-like sequence and a short ORF, have been identified. Because human IRS has previously been shown to be the target of antibodies in autoimmune disease, we discuss the role of protein structural features in the development of an autoimmune response to IRS. RP NICHOLS, RC (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,ROOM 9N244,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 13 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 APR 3 PY 1995 VL 155 IS 2 BP 299 EP 304 DI 10.1016/0378-1119(94)00634-5 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QT085 UT WOS:A1995QT08500027 PM 7721108 ER PT J AU ANTONUCCI, JM SKRTIC, D EANES, ED AF ANTONUCCI, JM SKRTIC, D EANES, ED TI REMINERALIZING DENTAL COMPOSITES BASED ON AMORPHOUS CALCIUM-PHOSPHATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIST,DIV POLYMERS,GAITHERSBURG,MD 20899. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 6 EP MACR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP233 UT WOS:A1995QP23302028 ER PT J AU BURKE, TR YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP AF BURKE, TR YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP TI NON-PHOSPHORUS-CONTAINING PHOSPHOTYROSYL MIMETICS AMENABLE TO PRODRUG DERIVATIZATION AND THEIR USE IN SOLID-PHASE SYNTHESIS OF SH2 DOMAIN AND PHOSPHATASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA,GRC,LCP,DIABET UNIT,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 14 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203207 ER PT J AU SHARMA, R WANG, S LEWIN, N BLUMBERG, PM MARQUEZ, VE AF SHARMA, R WANG, S LEWIN, N BLUMBERG, PM MARQUEZ, VE TI 1,3-PROPANESULTONES AS TEMPLATES FOR THE CONSTRUCTION OF NOVEL PROTEIN-KINASE-C (PK-C) AGONISTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DTP,DCT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 23 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203216 ER PT J AU YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP BURKE, TR AF YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP BURKE, TR TI DESIGN AND SYNTHESIS OF NON PHOSPHORUS-CONTAINING PHOSPHOTYROSYL MIMETICS FOR THE SOLID-PHASE SYNTHESIS OF SH2 DOMAIN AND PHOSPHATASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA,GRC,LCP,DIABET UNIT,BALTIMORE,MD 21224. NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,DCT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 24 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203217 ER PT J AU BAL, W LUKSZO, J JEZOWSKABOJCZUK, M KASPRZAK, KS AF BAL, W LUKSZO, J JEZOWSKABOJCZUK, M KASPRZAK, KS TI STRUCTURAL AND MECHANISTIC STUDIES OF NI(II) INTERACTIONS WITH CH3CO-CYS-ALA-ILE-HIS-NH2, A PROSPECTIVE TRANSITION-METAL BINDING MOTIF OF HISTONE H3 RELEVANCE TO CARCINOGENESIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,COMPARAT CARCINOGENES LAB,FREDERICK,MD 21702. NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. UNIV WROCLAW,INST CHEM,PL-50137 WROCLAW,POLAND. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 29 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203222 ER PT J AU BROOKS, BR AF BROOKS, BR TI ADVANCED METHODS FOR MACROMOLECULAR SIMULATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 37 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23201798 ER PT J AU BRYANT, SH AF BRYANT, SH TI AN INTEGRATED DATABASE OF BIOLOGICAL SEQUENCES, SCIENTIFIC LITERATURE, AND 3-DIMENSIONAL STRUCTURE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 46 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23201445 ER PT J AU ACKERMAN, MJ AF ACKERMAN, MJ TI THE TOXICOLOGY AND ENVIRONMENTAL-HEALTH INFORMATION PROGRAM OF THE NATIONAL-LIBRARY-OF-MEDICINE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 52 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23201451 ER PT J AU BEHAR, MG AF BEHAR, MG TI SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY-TRANSFER (STTR) PROGRAMS AT NATIONAL-INSTITUTES-OF-HEALTH (NIH) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,DIV RES GRANTS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 83 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200364 ER PT J AU SHAH, JH IZENWASSER, S WITKIN, JM GETERDOUGLASS, B NEWMAN, AH AF SHAH, JH IZENWASSER, S WITKIN, JM GETERDOUGLASS, B NEWMAN, AH TI N-CINNAMYL(4'-N,N-DIMETHYLAMINO)BENZAZEPINE ANALOGS ARE POTENT AND SELECTIVE DOPAMINE-D1 RECEPTOR LIGANDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,PSYCHOBIOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 85 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203278 ER PT J AU SIDDIQI, SM BOYER, JL VANRHEE, AM HARDEN, TK JACOBSON, KA AF SIDDIQI, SM BOYER, JL VANRHEE, AM HARDEN, TK JACOBSON, KA TI STRUCTURE-ACTIVITY-RELATIONSHIPS FOR 2-SUBSTITUTED ADENOSINE 5'-MONOPHOSPHATES AS AGONISTS AT P2Y PURINOCEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT LAB,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 86 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203279 ER PT J AU KIM, HO JI, XD MELMAN, N STILES, GL JACOBSON, KA AF KIM, HO JI, XD MELMAN, N STILES, GL JACOBSON, KA TI SELECTIVE LIGANDS FOR RAT A3 ADENOSINE RECEPTORS - STRUCTURE-ACTIVITY-RELATIONSHIPS OF 1,3-DIALKYLXANTHINE 7-RIBOSIDE DERIVATIVES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKA,BIOORGAN CHEM,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED & PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 87 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203280 ER PT J AU KIM, HO JI, XD SIDDIQI, SM OLAH, ME STILES, GL JACOBSON, KA AF KIM, HO JI, XD SIDDIQI, SM OLAH, ME STILES, GL JACOBSON, KA TI 2-SUBSTITUTION OF N6-BENZYLADENOSINE-5'-URONAMIDES ENHANCES SELECTIVITY FOR RAT A3 RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED & PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 88 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203281 ER PT J AU GU, ZQ STURGESS, MA HESSON, DP ZHOU, LM AF GU, ZQ STURGESS, MA HESSON, DP ZHOU, LM TI STEREOSELECTIVE SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 4-ALKYLGLUTAMIC ACIDS AT NMDA, AMPA AND KAINATE RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SYMPHONY PHARMACEUT INC,DEPT MED CHEM,MALVERN,PA 19355. SYMPHONY PHARMACEUT INC,DEPT PHARMACOL,MALVERO,PA 19355. NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 89 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203282 ER PT J AU QASBA, PK BALAJI, PV RAO, VSR AF QASBA, PK BALAJI, PV RAO, VSR TI MOLECULAR-DYNAMICS SIMULATIONS OF OLIGOSACCHARIDES AND THEIR CONFORMATION IN LECTIN-CARBOHYDRATE COMPLEXES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCBDC,MATH BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 101 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200762 ER PT J AU PATTABIRAMAN, N GUSSIO, R B, CKHITE, RW ZAHAREVITZ, D ERICKSON, JW AF PATTABIRAMAN, N GUSSIO, R B, CKHITE, RW ZAHAREVITZ, D ERICKSON, JW TI MOLECULAR MODELING STUDIES OF A NOVEL CLASS OF REVERSE-TRANSCRIPTASE (RT) INHIBITORS - CALANOLIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,FREDERICK BIOMED SUPERCOMP CTR,PRI DYNCORP,FREDERICK,MD 21702. SO RES INST,FREDERICK RES CTR,VIROL RES GRP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 106 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203299 ER PT J AU GUSSIO, R PATTABIRAMAN, N ZAHAREVITZ, DW KELLOGG, GE BURT, SK ERICKSON, JW AF GUSSIO, R PATTABIRAMAN, N ZAHAREVITZ, DW KELLOGG, GE BURT, SK ERICKSON, JW TI MODELING AND CLASSIFICATION OF CHEMICALLY UNRELATED HIV-1 NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. VIRGINIA COMMONWEALTH UNIV,DEPT MED CHEM,RICHMOND,VA 23284. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 107 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203300 ER PT J AU RANDAD, RS LUBKOWSKA, L SILVA, A BHAT, TN GULNIK, S YU, B ERICKSON, JW AF RANDAD, RS LUBKOWSKA, L SILVA, A BHAT, TN GULNIK, S YU, B ERICKSON, JW TI ITERATIVE STRUCTURE-BASED DESIGN OF POTENT, SYMMETRY BASED HIV PROTEASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,JW STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 112 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203305 ER PT J AU KIM, HY WANG, TC MA, YC AF KIM, HY WANG, TC MA, YC TI CHARACTERIZATION OF POLYUNSATURATED PHOSPHOLIPID REMODELING IN MAMMALIAN-CELLS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 125 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200406 ER PT J AU BOYER, PL TANTILLO, C DING, JP FERRIS, AL CLARK, P ARNOLD, E HUGHES, SH AF BOYER, PL TANTILLO, C DING, JP FERRIS, AL CLARK, P ARNOLD, E HUGHES, SH TI MECHANISMS OF RESISTANCE OF HIV-1 RT TO NUCLEOSIDE AND NONNUCLEOSIDE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PRI,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 150 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203343 ER PT J AU HOLMAN, MR AF HOLMAN, MR TI CAPILLARY ELECTROPHORESIS OF BIOLOGICAL SAMPLES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,ECRDC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 188 EP CHED PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23201052 ER PT J AU BOURASSA, JL MITCHELL, JB WINK, DA DEGRAFF, W FORD, PC AF BOURASSA, JL MITCHELL, JB WINK, DA DEGRAFF, W FORD, PC TI PHOTOCHEMISTRY OF FE-S-NO CLUSTERS - ROUSSINS SALTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. NIH,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 355 EP INOR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23202954 ER PT J AU TORCHIA, DA YAMAZAKI, T NICHOLSON, LK GRZESIEK, S BAX, A STAHL, SJ WINGFIELD, PT KAUFMAN, JD CHANG, CH WEBER, PC DOMAILLE, PJ LAM, PYS AF TORCHIA, DA YAMAZAKI, T NICHOLSON, LK GRZESIEK, S BAX, A STAHL, SJ WINGFIELD, PT KAUFMAN, JD CHANG, CH WEBER, PC DOMAILLE, PJ LAM, PYS TI STRUCTURE, DYNAMICS AND INTERACTIONS OF HIV-1 PROTEASE-INHIBITOR COMPLEXES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 19 EP 19 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500044 ER PT J AU LODI, PJ GARRETT, DS KUSZEWSKI, J TSANG, MLS WEATHERBEE, JA GRONENBORN, AM CLORE, GM AF LODI, PJ GARRETT, DS KUSZEWSKI, J TSANG, MLS WEATHERBEE, JA GRONENBORN, AM CLORE, GM TI THE 3-DIMENSIONAL STRUCTURE OF THE CYTOKINE HMIP-1-BETA AND COMPARISON TO THE RELATED CYTOKINE IL-8 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 28 EP 28 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500076 ER PT J AU QIN, J CLORE, GM HUTH, J KENNEDY, WP GRONENBORN, AM AF QIN, J CLORE, GM HUTH, J KENNEDY, WP GRONENBORN, AM TI THE 3-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN THIOREDOXIN COMPLEXED WITH ITS TARGEG BINDING-SITE FROM NFKB SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 36 EP 36 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500105 ER PT J AU CLUBB, R HUTH, J OMICHINSKI, JG SAVILAHTI, H MIZUUCHI, K GRONENBORN, AM CLORE, GM AF CLUBB, R HUTH, J OMICHINSKI, JG SAVILAHTI, H MIZUUCHI, K GRONENBORN, AM CLORE, GM TI INVESTIGATIONS OF THE DNA-BINDING DOMAIN OF TRANSPOSASE - BACKBONE DYNAMICS AND MUTAGENESIS STUDIES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 56 EP 56 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500183 ER PT J AU OMICHINSKI, JG GRONENBORN, AM TRAINOR, C STAHL, S FELSENFELD, G CLORE, GM AF OMICHINSKI, JG GRONENBORN, AM TRAINOR, C STAHL, S FELSENFELD, G CLORE, GM TI DNA-BINDING AND HETERONUCLEAR NMR-STUDIES WITH SINGLE AND DOUBLE ZINC-FINGER PEPTIDES FROM GATA-1 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 62 EP 62 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500209 ER EF