FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU HOFF, R
   BARKER, LF
AF HOFF, R
   BARKER, LF
TI TRIAL OBJECTIVES AND END-POINTS FOR MEASURING THE EFFICACY OF HIV
   VACCINES
SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY
LA English
DT Article
DE HUMAN IMMUNODEFICIENCY VIRUS VACCINES; TRIAL OBJECTIVES; END POINTS;
   EFFICACY
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS VACCINES; HEPATITIS-B; VACCINATION;
   PROGRESS; CHALLENGES; PREVENTION; DISEASE
AB In order to prove the efficacy of human immunodeficiency virus (HIV) vaccines, it will be necessary to do large-scale trials in populations at high risk of acquiring HIV infection. The choice of objectives and end points and their measurement will be key to the design of efficacy trials. To address these issues, the National Institute of Allergy and Infectious Diseases convened several workshops and discussions at national meetings. These discussions have concluded that many factors will contribute to the selection of practical primary objectives and end points for efficacy trials of HIV vaccines. For initial trials the objective of preventing the establishment of chronic infection is a reasonable choice, given the current state of knowledge. However, given the complexities of HIV and the acquired immunodeficiency syndrome, it will be important to collect data and evaluate other potential objectives and end points as well.
RP HOFF, R (reprint author), NIAID,DIV AIDS,VACCINE & PREVENT RES PROGRAM,SOLAR BLDG,RM 2A12,BETHESDA,MD 20892, USA.
NR 29
TC 14
Z9 14
U1 0
U2 0
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 1056-2044
J9 INFECT AGENT DIS
JI Infect. Agents Dis.-Rev. Issues Comment.
PD JUN
PY 1995
VL 4
IS 2
BP 95
EP 101
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA QZ195
UT WOS:A1995QZ19500004
PM 7613732
ER

PT J
AU BAKACS, T
   LEE, J
   MORENO, MB
   ZACHARCHUK, CM
   COLE, MS
   TSO, JY
   PAIK, CH
   WARD, JM
   SEGAL, DM
AF BAKACS, T
   LEE, J
   MORENO, MB
   ZACHARCHUK, CM
   COLE, MS
   TSO, JY
   PAIK, CH
   WARD, JM
   SEGAL, DM
TI A BISPECIFIC ANTIBODY PROLONGS SURVIVAL IN MICE BEARING LUNG METASTASES
   OF SYNGENEIC MAMMARY ADENOCARCINOMA
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE BLOOD; CANCER; CD3; CLEARANCE; MODEL; MOUSE; SURVIVAL; THERAPY
ID COLON-CARCINOMA MODEL; HUMAN OVARIAN-CARCINOMA; HUMAN LYMPHOCYTES-T;
   B-CELL LYMPHOMA; MONOCLONAL-ANTIBODIES; TUMOR NEUTRALIZATION; X
   ANTI-CD3; BIODISTRIBUTION; ACTIVATION; XENOGRAFTS
AB In the present study we tested whether T cells retargeted with a bispecific antibody (bsAb) could block the growth of lung metastases of syngeneic mammary adenocarcinoma in immunocompetent mice. BALB/c mice were injected i.v. with tumor and i.p. with a genetically engineered bispecific F(ab')(2) [bs(Fab')(2)] having specificity for murine CD3 epsilon chain and for the gp52 mouse mammary tumor viral glycoprotein, which is expressed on the tumor cells. The bs(Fab')(2) was physically stable in blood and serum, was removed from the body with a half-time of 12-15 h, and accumulated in lymphoid tissue where it bound to T cells. We show that treatment of tumor bearing mice with the bs(fab')(2) significantly prolonged their survival relative to untreated controls. Two other genetically engineered bs(fab')(2)s having specificity for murine CD3 epsilon chain and irrelevant antigens did not inhibit tumor growth. In addition, survival was not affected by bsAb therapy using a variant tumor cell line that expressed low levels of the gp52 target antigen. Inhibition of tumor growth was even more evident by histologic analysis. Treatment with the relevant bs(fab')(2) resulted in a marked reduction of tumor burden in lung sections taken on days 7, 9 and 11. This is the first report demonstrating that a bsAb can inhibit the growth of syngeneic solid tumor metastases in mice without addition of T cell activators.
C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892.
   NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892.
   NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892.
   PROT DESIGN LABS INC,MT VIEW,CA 94043.
   NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702.
NR 37
TC 8
Z9 8
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 JUN
PY 1995
VL 7
IS 6
BP 947
EP 955
DI 10.1093/intimm/7.6.947
PG 9
WC Immunology
SC Immunology
GA RF403
UT WOS:A1995RF40300007
PM 7577803
ER

PT J
AU FEAGANS, LV
   FENDT, K
   FARRAN, DC
AF FEAGANS, LV
   FENDT, K
   FARRAN, DC
TI THE EFFECTS OF DAY-CARE INTERVENTION ON TEACHERS RATINGS OF THE
   ELEMENTARY-SCHOOL DISCOURSE SKILLS IN DISADVANTAGED-CHILDREN
SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT
LA English
DT Article
ID ACHIEVEMENT; GRADE; INFANTS
AB The aim of this study was to assess whether a day care intervention programme for children from impoverished backgrounds could affect teacher's ratings of their language use in the classroom in early elementary school.  There were 32 experimental children (who had received a day care intervention programme) and 36 control children in the initial study.  At school entry, a comparison child from the same classroom was selected for each of the experimental and control children.  The children were followed for three years in school.  Besides collecting IQ and achievement data, teachers were asked to fill out the Adaptive Language Inventory (ALI) which measured children's use of language in narrative and discourse situations in the classroom.  The results indicated that although the comparison group was rated more highly than the experimental and the control group, the experimental group was rated more favourably than the control group over all three years on three of the four major scales of the ALI.  There was no indication of a decrease in the size of effects by year 3.  Regression analyses generally indicated that the ALI was moderately related to verbal IQ and highly related to reading recognition and comprehension concurrently and over three years.  The results suggest that an early intervention programme can be effective in changing and maintaining teachers' perceptions of the narrative and discourse skills of children through early elementary school.  In addition, the study suggests that these narrative and discourse skills may be important for reading and other verbal abilities.
C1 NICHHD,ROCKVILLE,MD.
   UNIV N CAROLINA,GREENSBORO,NC 27412.
RP FEAGANS, LV (reprint author), PENN STATE UNIV,DEPT HUMAN DEV & FAMILY STUDIES,S-110 HENDERSON BLDG,UNIVERSITY PK,PA 16802, USA.
NR 39
TC 14
Z9 14
U1 0
U2 1
PU LAWRENCE ERLBAUM ASSOC LTD
PI HOVE
PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA
SN 0165-0254
J9 INT J BEHAV DEV
JI Int. J. Behav. Dev.
PD JUN
PY 1995
VL 18
IS 2
BP 243
EP 261
PG 19
WC Psychology, Developmental
SC Psychology
GA RC606
UT WOS:A1995RC60600004
ER

PT J
AU BRENNEMAN, DE
   HILL, JM
   GLAZNER, GW
   GOZES, I
   PHILLIPS, TW
AF BRENNEMAN, DE
   HILL, JM
   GLAZNER, GW
   GOZES, I
   PHILLIPS, TW
TI INTERLEUKIN-1-ALPHA AND VASOACTIVE-INTESTINAL-PEPTIDE - ENIGMATIC
   REGULATION OF NEURONAL SURVIVAL
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Article
DE INTERLEUKIN-1-ALPHA; NEURONAL SURVIVAL; VIP-IL-1 RELATIONSHIP
ID CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD CULTURES; RECEPTOR ANTAGONIST;
   ELECTRICAL-ACTIVITY; NEUROTROPHIC ACTION; MESSENGER-RNA; HUMAN BRAIN;
   RAT; INVOLVEMENT; CELLS
AB A neurotrophic role for interleukin-1 alpha (IL-1 alpha) was investigated in dissociated spinal cord-dorsal root ganglion cultures. Three observations suggested a survival-promoting action for IL-1 alpha in nine-day-old cultures: (1) neutralizing antiserum to murine IL-1 alpha decreased neuronal survival; (2) treatment with IL-1 alpha in electrically blocked cultures increased neuronal survival; and (3) antiserum to the type I IL-1 receptor decreased neuronal survival. Treatment with VIP prevented neuronal cell death associated with the antiserum to IL-1 alpha. In contrast, treatment of one-month-old cultures with IL-1 alpha produced neuronal cell death and neutralizing antiserum to the IL-1 receptor had no effect on neuronal survival in these cultures. These experiments suggested that an IL-1 like substance was necessary for neuronal survival during a specific stage in development and that a relationship between VIP and IL-1 alpha might account in part for the neurotrophic properties of VIP.
   To test if VIP might be a secretagogue for IL-1, a neuron-free model system was utilized: astroglial cultures derived from cerebral cortex. VIP treatment produced a concentration-dependent (EC50:50 pM) increase in the amount of IL-1 alpha in the medium and a decrease in cellular IL-1 alpha. Interleukin-1 beta (IL-1 beta) was also increased (EC 50: 1 nM) in the medium by VIP but without depleting IL-1 beta in the cytosol. Semi-quantitative measurements of the IL-1 alpha mRNA after VIP treatment indicated a significant but transient decrease. These data indicate that VIP produced an increase in the secretion of IL-1 alpha while depleting IL-1 alpha mRNA.
C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL.
   WASHINGTON UNIV,CTR MED,DEPT MED,IMMUNOCHEM LAB,WASHINGTON,DC.
RP BRENNEMAN, DE (reprint author), NICHHD,LDN,SDMP,BLDG 49,ROOM 5A38,BETHESDA,MD 20892, USA.
NR 49
TC 74
Z9 75
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0736-5748
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD JUN-JUL
PY 1995
VL 13
IS 3-4
BP 187
EP 200
DI 10.1016/0736-5748(95)00014-8
PG 14
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA RG088
UT WOS:A1995RG08800007
PM 7572275
ER

PT J
AU STEINDORF, K
   LUBIN, J
   WICHMANN, HE
   BECHER, H
AF STEINDORF, K
   LUBIN, J
   WICHMANN, HE
   BECHER, H
TI LUNG-CANCER DEATHS ATTRIBUTABLE TO INDOOR RADON EXPOSURE IN WEST-GERMANY
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
ID URANIUM MINERS; UNITED-STATES; RISK
AB Background. There is substantial epidemiological and experimental evidence that exposure to radon at levels found in underground mines can cause lung cancer. Although radon levels measured in homes are normally substantially lower, there is concern about the presence of a known lung carcinogen in a residential setting.
   Methods. Using national survey data on radon concentrations in homes in the former West Germany, the proportion and absolute numbers of lung cancer deaths attributable to radon are estimated. As lung cancer risk models derived directly from residential radon studies are not yet available, the risk model developed recently by Lubin et al. from a joint analysis of 11 underground miners' studies is applied. For an estimate of the impact of smoking on radon-attributable lung cancers, three different approaches are used and compared.
   Results. Our analysis shows that after adjusting for dosimetry differences between mines and homes about 7% of all lung cancer deaths in the western part of Germany may be due to residential radon. This corresponds to a total of about 2000 deaths (95% Cl:500-8200), 400 in females and 1600 in males. Adjusting for the intermediate relationship for smoking and radon, the attributable risk is estimated to be about 4-7% for smokers and 14-22% in non-smokers.
   Conclusions. Our analysis basically confirms the results of former calculations with regard to the total number of lung cancer deaths attributable to radon in West Germany. However, we show that the standard practice that applies the same model to smokers and non-smokers may result in biased estimates for these groups.
C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892.
   GSF MUNICH,ENVIRONM & HLTH RES CTR,INST EPIDEMIOL,NEUHERBERG,GERMANY.
RP STEINDORF, K (reprint author), GERMAN CANC RES CTR,DIV EPIDEMIOL 0345,POB 101949,D-69009 HEIDELBERG,GERMANY.
NR 30
TC 20
Z9 25
U1 0
U2 3
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD JUN
PY 1995
VL 24
IS 3
BP 485
EP 492
DI 10.1093/ije/24.3.485
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA RF212
UT WOS:A1995RF21200002
PM 7672886
ER

PT J
AU DUYN, JH
   FRANK, JA
   RAMSEY, NR
   MATTAY, VS
   SEXTON, RH
   TALLENT, KA
   WEINBERGER, DR
   MOONEN, CTW
   VANGELDEREN, P
AF DUYN, JH
   FRANK, JA
   RAMSEY, NR
   MATTAY, VS
   SEXTON, RH
   TALLENT, KA
   WEINBERGER, DR
   MOONEN, CTW
   VANGELDEREN, P
TI EFFECTS OF LARGE VESSELS IN FUNCTIONAL MAGNETIC-RESONANCE-IMAGING AT 1.5
   T
SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
LA English
DT Article
ID HUMAN VISUAL-CORTEX; SENSORY STIMULATION; BRAIN; CONTRAST; OXYGENATION;
   SIGNAL; ACTIVATION; EPI
AB To further investigate the effects of large vessels on the activation maps generated with functional magnetic resonance imaging at 1.5 T, we studied activation of the human visual and motor cortex using a multitude of dedicated FLASH and echo-planar imaging (EPI) scanning techniques. Both slice and volume scans were performed to assess relative contributions of T-2* effects, in-flow, and phase-shift effects, specifically within and around the larger vessels (around 1 mm in diameter). The contrast mechanism in single-slice FLASH studies appeared to be predominantly sensitive to in-flow and phase effects of the blood water within these larger vessels, and their relative contributions were dependent on experimental parameters and vascular geometry. The contrast mechanism in gradient echo EPI studies was governed predominantly by T-2* effects in tissue water (and to a lesser extent cerebrospinal fluid) surrounding the larger vessels. (C) 1995 John Wiley & Sons, Inc.
C1 NIMH, CLIN BRAIN DISORDERS BRANCH, BETHESDA, MD 20892 USA.
   NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, INVIVO NMR RES CTR, BETHESDA, MD 20892 USA.
RP NIH, DIAGNOST RADIOL RES LAB, OD OIR, BLDG 10, ROOM B1N-256, BETHESDA, MD 20892 USA.
RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016
OI Moonen, Chrit/0000-0001-5593-3121
NR 15
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-9457
EI 1098-1098
J9 INT J IMAG SYST TECH
JI Int. J. Imaging Syst. Technol.
PD SUM-FAL
PY 1995
VL 6
IS 2-3
BP 245
EP 252
DI 10.1002/ima.1850060216
PG 8
WC Engineering, Electrical & Electronic; Optics; Imaging Science &
   Photographic Technology
SC Engineering; Optics; Imaging Science & Photographic Technology
GA TG991
UT WOS:A1995TG99100015
ER

PT J
AU PEEHL, DM
   WONG, ST
   RHIM, JS
AF PEEHL, DM
   WONG, ST
   RHIM, JS
TI ALTERED GROWTH-REGULATION OF PROSTATIC EPITHELIAL-CELLS BY HUMAN
   PAPILLOMAVIRUS-INDUCED TRANSFORMATION
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE PROSTATE; PAPILLOMAVIRUS; SIMIAN VIRUS-40; TRANSFORMATION
ID SERUM-FREE GROWTH; HUMAN KERATINOCYTES; CLONAL GROWTH; NEOPLASTIC
   TRANSFORMATION; PITUITARY EXTRACT; PRIMARY CULTURES; CARCINOMA CELLS;
   RETINOIC ACID; TYPE-16; IMMORTALIZATION
AB Six lines of human papillomavirus (HPV)-transformed prostatic epithelial cells, clonally-derived from transfection of three different parental cell strains, were analyzed for their ability to respond to stimulatory and inhibitory factors known to regulate prostatic cell growth. The cell lines were tested in a serum-free medium that was developed specifically for analysis of low-density growth of prostatic cells in order to mitigate any effects of autocrine factors. This medium has been used previously to characterize the growth regulatory pathways of primary cultures of prostatic epithelial cells derived from normal, benign prostatic hyperplasia (BPH), or adenocarcinoma tissues, as well as an SV40-transformed cell line (pRNS-1-1) that was derived from the same parental cell strain as four of the HPV-transformed lines used in the present study. The responses of the HPV-transformed cell lines to three essential mitogens in the medium - epidermal growth factor (EGF), bovine pituitary extract (BPE) and insulin-like growth factor (IGF) - were similar to those of primary cultures and pRNS-1-1, except that two of the HPV-transformed cell lines were IGF-independent for growth. The presence or absence of cholera toxin (CT), which acts synergistically with peptide growth factors, only mildly affected the proliferation of HPV-transformed cells, which is also true for primary cultures and pRNS-1-1. However, while hydrocortisone (HC) also has only minimal effect on the growth of primary cultures and pRNS-1-1, four of the HPV-transformed lines were very dependent on HC for growth. With regard to growth-inhibitory factors, all of the cell lines (HPV- or SV40- transformed) were insensitive to tumor necrosis factor-alpha (TNFalpha), which is a common feature of transformed cells. However, the cell lines remained sensitive to the growth-inhibitory properties of retinoic acid (RA) and transforming growth factor-beta (TGF(beta)). The HPV-transformed cell lines were also inhibited by 1,25(OH)(2) vitamin D-3 [1,25(OH)(2)D-3], although pRNS-1-1 cells were not. Perhaps the most unexpected finding in our study was the apparent loss of responsiveness of all of the transformed lines to fibroblast growth factor (FGF). Alterations in FGF pathways have been described for prostatic cancer cell lines and changes in expression of FGF or receptors may be involved in prostatic carcinogenesis. Our study demonstrates that the availability of primary cultures, SV40- and HPV- transformed cell lines and a well-defined culture system will provide an opportunity to characterize the processes involved in malignant transformation of prostatic cells.
C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702.
RP PEEHL, DM (reprint author), STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305, USA.
NR 44
TC 8
Z9 8
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 JUN
PY 1995
VL 6
IS 6
BP 1177
EP 1184
PG 8
WC Oncology
SC Oncology
GA QZ597
UT WOS:A1995QZ59700005
PM 21556655
ER

PT J
AU MUANZA, DN
   EULER, KL
   WILLIAMS, L
   NEWMAN, DJ
AF MUANZA, DN
   EULER, KL
   WILLIAMS, L
   NEWMAN, DJ
TI SCREENING FOR ANTITUMOR AND ANTI-HIV ACTIVITIES OF 9 MEDICINAL-PLANTS
   FROM ZAIRE
SO INTERNATIONAL JOURNAL OF PHARMACOGNOSY
LA English
DT Article
DE BIOLOGICAL ACTIVITY; ANTITUMOR; ANTI-HIV; MEDICINAL PLANTS; ZAIRE
AB The evaluation of anticancer and anti-HIV activities of extracts from nine medicinal plants collected in Zaire was carried out against the National Cancel Institute (NCI) panel of human tumor cell lines provided for the preliminary screening of natural products The methanol extracts from the root bark of Hymenocardia acida, the stem bark of Mangifera indica and the leaves of Sida rhombifolia, exhibited cytotoxic activity, against the 60 human cell lines tested. Of these, the methanol extract from M. indica produced an interesting pattern of differential cellular sensitivity against the MDA-MB-231, MDA-MB-435, and MDA-N human breast cancer cell lines. In the AIDS-antiviral screen, the methanol extract from Jatropha curcas was found to produce a moderate cytoprotective effect against HIV in cultured human lymphoblastoid CEM-SS cells.
C1 UNIV HOUSTON,COLL PHARM,DEPT PHARMACOL & PHARMACEUT SCI,HOUSTON,TX 77204.
   NCI,FREDERICK CANC RES & DEV CTR,NAT PROD BRANCH,FREDERICK,MD 21702.
NR 11
TC 47
Z9 52
U1 1
U2 7
PU SWETS ZEITLINGER BV
PI LISSE
PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS
SN 0925-1618
J9 INT J PHARMACOGN
JI Int. J. Pharmacogn.
PD JUN
PY 1995
VL 33
IS 2
BP 98
EP 106
PG 9
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA TF518
UT WOS:A1995TF51800002
ER

PT J
AU TEIGEN, PM
AF TEIGEN, PM
TI THE WINNING OF ANIMAL HEALTH - 100 YEARS OF VETERINARY-MEDICINE -
   STALHEIM,OHV
SO ISIS
LA English
DT Book Review
RP TEIGEN, PM (reprint author), NATL LIB MED,DIV HIST MED,BETHESDA,MD 20209, USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 0021-1753
J9 ISIS
JI Isis
PD JUN
PY 1995
VL 86
IS 2
BP 345
EP 345
DI 10.1086/357214
PG 1
WC History & Philosophy Of Science
SC History & Philosophy of Science
GA RP895
UT WOS:A1995RP89500073
ER

PT J
AU PALMER, MH
AF PALMER, MH
TI NURSES KNOWLEDGE AND BELIEFS ABOUT CONTINENCE INTERVENTIONS IN
   LONG-TERM-CARE
SO JOURNAL OF ADVANCED NURSING
LA English
DT Article
ID NURSING-HOME RESIDENTS; URINARY-INCONTINENCE; MANAGEMENT; QUALITY
AB Incontinence in nursing homes is a prevalent condition requiring a programmatic approach due to its diverse aetiology. Awareness of antecedent factors, such as knowledge and beliefs about incontinence and its treatment by the individuals responsible for establishing and maintaining a continence programme, is important prior to implementation. A questionnaire was administered to licensed nurses who attended a workshop on urinary incontinence in nursing homes. One purpose of the questionnaire was to elicit information about beliefs regarding the effects of continence programmes on residents and staff and potential staff reaction to implementation of a continence programme in their facility. Responses by licensed practical nurses (LPNs) were compared to the responses of registered nurses (RNs). Attribution for causes of incontinence differed between LPNs and RNs. There were no significant differences in the report of current routine nursing care which included scheduled toileting, changing clothing when necessary, and use of adult briefs and underpads. Most nurses anticipated a favourable reaction by the staff to the implementation of a continence programme. However, at least 20% responded that the nursing staff would be apathetic or resistant to a programme. Administrative support was infrequently chosen as the most important factor in the implementation of a programme. The implications of these findings to continence programmes that are integrated into the organization and provide comprehensive services, including preventive interventions, are discussed.
C1 NATL INST NURSING RES,CLIN THERAPEUT LAB,BALTIMORE,MD.
NR 26
TC 30
Z9 30
U1 1
U2 2
PU BLACKWELL SCIENCE LTD
PI OXFORD
PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL
SN 0309-2402
J9 J ADV NURS
JI J. Adv. Nurs.
PD JUN
PY 1995
VL 21
IS 6
BP 1065
EP 1072
DI 10.1046/j.1365-2648.1995.21061065.x
PG 8
WC Nursing
SC Nursing
GA RA019
UT WOS:A1995RA01900006
PM 7665769
ER

PT J
AU WANG, AC
   GRZESIEK, S
   TSCHUDIN, R
   LODI, PJ
   BAX, A
AF WANG, AC
   GRZESIEK, S
   TSCHUDIN, R
   LODI, PJ
   BAX, A
TI SEQUENTIAL BACKBONE ASSIGNMENT OF ISOTOPICALLY ENRICHED PROTEINS IN D2O
   BY DEUTERIUM-DECOUPLED HA(CA)N AND HA(CACO)N
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE DEUTERIUM; TRIPLE RESONANCE; ISOTOPE LABELING; SEQUENTIAL ASSIGNMENT;
   UBIQUITIN
ID TRIPLE-RESONANCE NMR; HUMAN UBIQUITIN; POLARIZATION TRANSFER; LARGER
   PROTEINS; SPECTROSCOPY; SPECTRA; ENHANCEMENT; C-13; RESOLUTION; H-1-NMR
AB It is demonstrated that sequential resonance assignment of the backbone H-1(alpha) and N-15 resonances of proteins can be obtained without recourse to the backbone amide protons, an approach which should be useful for assignment of regions with rapidly exchanging backbone amide protons and for proteins rich in proline residues. The method relies on the combined use of two 2D experiments, HA(CA)N and HA(CACO)N or their 3D analogs, which correlate H-1(alpha) with the intraresidue N-15 and with the N-15 resonance of the next residue. The experiments are preferably conducted in D2O, where very high resolution in the N-15 dimension can be achieved by using ?a decoupling. The approach is demonstrated for a sample of human ubiquitin, uniformly enriched in C-13 and N-15. Complete backbone and C-13(beta)/H-1(beta) resonance assignments are presented.
RP WANG, AC (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA.
NR 28
TC 87
Z9 88
U1 1
U2 5
PU ESCOM SCI PUBL BV
PI LEIDEN
PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JUN
PY 1995
VL 5
IS 4
BP 376
EP 382
PG 7
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA RJ884
UT WOS:A1995RJ88400008
PM 7647557
ER

PT J
AU NAUSS, JL
   REID, RH
   SADEGHNASSERI, S
AF NAUSS, JL
   REID, RH
   SADEGHNASSERI, S
TI ACCURACY OF A STRUCTURAL HOMOLOGY MODEL FOR A CLASS-II
   HISTOCOMPATIBILITY PROTEIN, HLA-DR1 - COMPARISON TO THE
   CRYSTAL-STRUCTURE
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Article
ID T-CELL EPITOPE; PEPTIDE ANTIGENS; 3-DIMENSIONAL STRUCTURE; MHC; BINDING;
   MOLECULES; RECOGNITION; COMPLEX; POLYMORPHISM; HLA-B27
AB Structural homology modeling is used to test the accuracy by which a Class I major histocompatibility complex (MHC) could be used to model a Class II MHC. The crystal structure of HLA-aw68 served as a reference molecule to model HLA-DR1. The resulting model was compared to the recently released crystal structure by Brown et al. (Nature, Vol. 364, p. 33-39 (1993)). The overall tertiary structure motif(two alpha-helices and a beta-sheet forming a peptide binding cleft) was maintained. However, significant deviations in the secondary structure elements were found between the model and the DR1 crystal structure. These deviations were consistent with the differences between Class I and Class II crystal structures. In regions where the model and DR1 crystal structures are most similar, side chain orientations are also similar. Specific peptide-MHC interactions are discussed and compared with the crystal structure results.
C1 WALTER REED ARMY INST RES,DEPT GASTROENTEROL,DIV MED,WASHINGTON,DC 20307.
   ORAVAX INC,CAMBRIDGE,ENGLAND.
   NIAID,LI,BETHESDA,MD 20892.
OI Sadegh-Nasseri, Scheherazade/0000-0002-8127-1720
NR 32
TC 4
Z9 4
U1 0
U2 1
PU ADENINE PRESS INC
PI GUILDERLAND
PA PO BOX 355/340, GUILDERLAND, NY 12084
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 1995
VL 12
IS 6
BP 1213
EP 1233
PG 21
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA RF744
UT WOS:A1995RF74400005
PM 7669268
ER

PT J
AU FITZGERALD, DJ
   FRYLING, CM
   ZDANOVSKY, A
   SAELINGER, CB
   KOUNNAS, M
   WINKLES, JA
   STRICKLAND, D
   LEPPLA, S
AF FITZGERALD, DJ
   FRYLING, CM
   ZDANOVSKY, A
   SAELINGER, CB
   KOUNNAS, M
   WINKLES, JA
   STRICKLAND, D
   LEPPLA, S
TI PSEUDOMONAS EXOTOXIN-MEDIATED SELECTION YIELDS CELLS WITH ALTERED
   EXPRESSION OF LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ALPHA-2-MACROGLOBULIN RECEPTOR; PLASMINOGEN-ACTIVATOR; ADP-RIBOSYLATION;
   DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; CHIMERIC TOXINS; COMPLEXES; CYTOSOL;
   MUTANTS; BINDS
AB The alpha(2)-macroglobulin (alpha(2)M) receptor/low-density lipoprotein receptor-related protein (LRP) is important for the clearance of proteases, protease-inhibitor complexes, and various ligands associated with lipid metabolism. While the regulation of receptor function is poorly understood, the addition of high concentrations of the 39-kD receptor-associated protein (RAP) to cells inhibits the binding and/or uptake of many of these ligands. Previously, we (Kounnas, M. Z., J. Henkin, W. S. Argraves, D. K. Strickland. 1992. J. Biol. Chem. 267:12420-12423) showed that Pseudomonas exotoxin (PE) could bind immobilized LRP. Also, the addition of RAP blocked toxin-mediated cell killing. These findings suggested that PE might use LRP to gain entry into toxin-sensitive cells. Here we report on a strategy to select PE-resistant lines of Chinese hamster ovary cells that express altered amounts of LRP. An important part of this strategy is to screen PE-resistant clones for those that retain sensitivity to both diphtheria toxin and to a fusion protein composed of lethal factor (from anthrax toxin) fused to the adenosine diphosphate-ribosylating domain of PE. Two lines, with obvious changes in their expression of LRP, were characterized in detail. The 14-2-1 line had significant amounts of LRP, but in contrast to wild-type cells, little or no receptor was displayed on the cell surface. Instead, receptor protein was found primarily within cells, much of it apparently in an unprocessed state. The 14-2-1 line showed no uptake of chymotrypsin-alpha(2)M and was 10-fold resistant to PE compared with wild-type cells. A second line, 13-5-1, had no detectable LRP mRNA or protein, did not internalize alpha(2)M-chymotrypsin, and exhibited a 100-fold resistance to PE. Resistance to PE appeared to be due to receptor-specific defects, since these mutant lines showed no resistance to a PE chimeric toxin that was internalized via the transferrin receptor. The results of this investigation confirm that LRP mediates the internalization of PE.
C1 UNIV CINCINNATI,DEPT MOLEC GENET,CINCINNATI,OH 45267.
   AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855.
   NIH,INST DENT,BETHESDA,MD 20892.
RP FITZGERALD, DJ (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37 4B-03,BETHESDA,MD 20892, USA.
FU NHLBI NIH HHS [HL50787, HL39727]; NIGMS NIH HHS [GM42581]
NR 41
TC 96
Z9 96
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 JUN
PY 1995
VL 129
IS 6
BP 1533
EP 1541
DI 10.1083/jcb.129.6.1533
PG 9
WC Cell Biology
SC Cell Biology
GA RD458
UT WOS:A1995RD45800008
PM 7790352
ER

PT J
AU KOBAYASHI, T
   VIEIRA, WD
   POTTERF, B
   SAKAI, C
   IMOKAWA, G
   HEARING, VJ
AF KOBAYASHI, T
   VIEIRA, WD
   POTTERF, B
   SAKAI, C
   IMOKAWA, G
   HEARING, VJ
TI MODULATION OF MELANOGENIC PROTEIN EXPRESSION DURING THE SWITCH FROM
   EUMELANOGENESIS TO PHEOMELANOGENESIS
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE TYROSINASE; TRP; SILVER PROTEIN; MELANIN; PIGMENTATION
ID HAIR FOLLICULAR MELANOCYTES; TYROSINASE-RELATED PROTEIN; MAMMALIAN
   TYROSINASE; DOPACHROME OXIDOREDUCTASE; MELANIN BIOSYNTHESIS; MURINE
   MELANOCYTES; AGOUTI GENE; MOUSE; MICE; LOCUS
AB Mammalian melanocytes can produce two basic types of melanin, eumelanin and pheomelanin, within discrete organelles termed melanosomes. The physiological signals that regulate this switch are extrinsic to the melanocyte, and include alpha-melanocyte stimulating hormone and the agouti protein. Tyrosinase, encoded at the albino locus, is the enzyme essential for the synthesis of both types of melanin, but other tyrosinase-related proteins (e.g. TRP1 encoded at the brown locus and TRP2 encoded at the slaty locus) regulate eumelanogenesis catalytically at steps distal to tyrosinase (as 5,6-dihydroxyindole-2-carboxylic acid oxidase and DOPAchrome tautomerase, respectively). The silver protein is another melanosomal protein, and although it has some limited homology to the tyrosinase-related proteins, it does not have any known enzymatic function and probably serves as a structural matrix protein. The role of each of those melanosomal proteins in pheomelanogenesis, however, is still unclear. In this study, we have compared the expression and catalytic functions of those proteins in pheomelanic and eumelanic hair bulb melanocytes. There was no detectable expression of TRP1 or TRP2, or either of their enzymatic activities, in hair bulbs of lethal yellow (Ay/a) newborn mice, and tyrosinase activity was present at a reduced level compared to that found in hair bulbs of black (a/a) newborn mice. Similar results were observed in regenerating hair bulbs of adult lethal yellow mice and in hair bulbs of 5- to 7-day-old agouti mice (A/A), an age where pheomelanin is produced predominantly, Expression of the silver protein was similarly not observed in hair bulbs of the pheomelanic mice. These results support the hypothesis that TRP1 and TRP2 may have only eumelanogenesis-specific functions and further suggest that the silver protein has a structural and/or unknown catalytic function that is similarly eumelanogenesis-specific. Expression of TRP1, TRP2 and/or the silver protein is not required for the switch to pheomelanogenesis, since their functions are specifically down-regulated by the action of the agouti protein, the physiological regulator of the switch to produce pheomelanin.
C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892.
   KAO CORP,INST FUNDAMENTAL RES,HAGA,TOCHIGI 32134,JAPAN.
NR 57
TC 127
Z9 131
U1 0
U2 4
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS,
   ENGLAND CB4 4DL
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUN
PY 1995
VL 108
BP 2301
EP 2309
PN 6
PG 9
WC Cell Biology
SC Cell Biology
GA RF828
UT WOS:A1995RF82800019
PM 7673350
ER

PT J
AU KING, KL
   CIDLOWSKI, JA
AF KING, KL
   CIDLOWSKI, JA
TI CELL-CYCLE AND APOPTOSIS - COMMON PATHWAYS TO LIFE AND DEATH
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE MITOSIS; MITOTIC CATASTROPHE; APOPTOSIS; CELL CYCLE COMPONENTS; CDC2
ID WILD-TYPE P53; C-MYC; INHIBITION; INDUCTION; MAINTAINS; PROTEIN
AB Programmed cell death, or apoptosis, is a highly regulated process used to eliminate unwanted or damaged cells from multicellular organisms. The morphology of cells undergoing apoptosis is similar to cells undergoing both normal mitosis and an aberrant form of mitosis called mitotic catastrophe. During each of these processes, cells release substrate attachments, lose cell volume, condense their chromatin, and disassemble the nuclear lamina. The morphological similarities among cells undergoing these processes suggest that the underlying biochemical changes also may be related. The susceptibility of cells to apoptosis frequently depends on the differentiation state of the cell. Additionally, cell cycle checkpoints appear to link the cell cycle to apoptosis. Deregulation of the cell cycle components has been shown to induce mitotic catastrophe and also may be involved in triggering apoptosis. Some apoptotic cells express abnormal levels of cell cycle proteins and often contain active Cdc2, the primary kinase active during mitosis. Although cell cycle components may not be involved in all forms of apoptosis, in many instances cell proliferation and cell death may share common pathways. (C) 1995 Wiley-Liss, Inc.*
C1 NIEHS,INTEGRAT BIOL LAB,RES TRIANGLE PK,NC 27709.
FU NIDDK NIH HHS [DK 32078]
NR 33
TC 311
Z9 327
U1 0
U2 7
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 JUN
PY 1995
VL 58
IS 2
BP 175
EP 180
DI 10.1002/jcb.240580206
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA RD134
UT WOS:A1995RD13400005
PM 7673325
ER

PT J
AU RINAUDO, JA
   VACCHIANO, E
   ZELENKA, PS
AF RINAUDO, JA
   VACCHIANO, E
   ZELENKA, PS
TI EFFECTS OF C-JUN AND A NEGATIVE DOMINANT MUTATION OF C-JUN ON
   DIFFERENTIATION AND GENE-EXPRESSION IN LENS EPITHELIAL-CELLS
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE PROTOONCOGENES; PROLIFERATION; CRYSTALLINS; AP-1; RETROVIRUS VECTORS
ID A-CRYSTALLIN GENE; TISSUE-SPECIFIC EXPRESSION; EMBRYONAL
   CARCINOMA-CELLS; CHICKEN LENS; MESSENGER-RNA; ENHANCER ELEMENT;
   CHAIN-REACTION; FOS PROTEINS; DNA-BINDING; TRANSCRIPTION
AB We have used a retroviral vector (RCAS) to overexpress wild-type chicken c-Jun or a deletion mutant of chicken c-Jun (Jun Delta 7) lacking the DNA binding region to investigate the possible role of c-Jun in lens epithelial cell proliferation and differentiation. Both constructs were efficiently expressed in primary cultures of embryonic chicken lens epithelial cells. Overexpression of c-Jun increased the rate of cell proliferation and greatly delayed the appearance of ''lentoid bodies,'' structures which contain differentiated cells expressing fiber cell markers. Excess c-jun expression also significantly decreased the level of beta(A3/A1)-crystallin mRNA, without affecting alpha A-crystallin mRNA. In contrast, the mutated protein, Jun Delta 7, had no effect on proliferation or differentiation but markedly increased the level of alpha A-crystal tin mRNA in proliferating cell cultures. These results suggest that c-Jun or Jun-related proteins may be negative regulators of alpha A- and B-A3/A1-crystallin genes in proliferating lens cells. (C) 1995 Wiley-Liss, Inc.*
RP RINAUDO, JA (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 214,BETHESDA,MD 20892, USA.
NR 47
TC 11
Z9 11
U1 0
U2 1
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JUN
PY 1995
VL 58
IS 2
BP 237
EP 247
DI 10.1002/jcb.240580212
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA RD134
UT WOS:A1995RD13400011
PM 7673330
ER

PT J
AU TARULLO, LB
   RICHARDSON, DT
   RADKEYARROW, M
   MARTINEZ, PE
AF TARULLO, LB
   RICHARDSON, DT
   RADKEYARROW, M
   MARTINEZ, PE
TI MULTIPLE SOURCES IN CHILD DIAGNOSIS - PARENT-CHILD CONCORDANCE IN
   AFFECTIVELY ILL AND WELL FAMILIES
SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY
LA English
DT Article
ID STRUCTURED PSYCHIATRIC INTERVIEW; MATERNAL DEPRESSION; FATHERS
   PERCEPTIONS; ASSESSMENT SCHEDULE; AGREEMENT; SYMPTOMS; MOTHERS;
   BEHAVIOR; VALIDITY; ADOLESCENTS
AB Examined parent-child and mother-father agreement on child disruptive, mood, and anxiety disorders as assessed by structured psychiatric interview.  As part of a large longitudinal project on affectively ill and well families, assessments were conducted for two siblings (ages 8 to 11 and 12 to 16).  The findings underscore the importance of taking into account age and sex of child, parental affective illness, and sex of parent in comparing child assessments from multiple sources.  For example, both mother-child and mother-father agreement were higher in the preadolescent than in the adolescent group.  Whereas preadolescent children in all maternal diagnostic groups reported presence of problems at similar rates, control mothers were far less likely to report child problems than either unipolar or bipolar mothers.  Fathers, whose psychiatric statuses were known, were used as criterion raters to test the possibility of distorted reporting by depressed mothers.  There was greater mother-child and mother-father agreement in families with an affectively ill mother and well father than in families with both parents well.  Thus, maternal depression, although an important variable in mother report, should not be assumed to be a distorting factor.
RP TARULLO, LB (reprint author), NIMH,BLDG 15-K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 44
TC 45
Z9 45
U1 0
U2 2
PU LAWRENCE ERLBAUM ASSOC INC
PI MAHWAH
PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262
SN 0047-228X
J9 J CLIN CHILD PSYCHOL
JI J. Clin. Child Psychol.
PD JUN
PY 1995
VL 24
IS 2
BP 173
EP 183
DI 10.1207/s15374424jccp2402_5
PG 11
WC Psychology, Clinical; Psychology, Developmental
SC Psychology
GA QW372
UT WOS:A1995QW37200006
ER

PT J
AU COUNTS, DR
   CUTLER, GB
AF COUNTS, DR
   CUTLER, GB
TI GROWTH-HORMONE INSENSITIVITY SYNDROME DUE TO POINT DELETION AND
   FRAME-SHIFT IN THE GROWTH-HORMONE RECEPTOR
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Note
ID LARON-TYPE DWARFISM
AB By direct amplification and sequencing of genomic DNA by the polymerase chain reaction, we have identified a unique 2-base deletion in the growth hormone receptor gene of a patient with extreme short stature and growth hormone insensitivity (Laron) syndrome. We found a deletion of bases 118 - 119 in exon 4, which corresponds to the extracellular domain of the growth hormone receptor. Since this mutation encodes a frameshift in the amino acid sequence and a stop codon relatively early in the translation of the growth hormone receptor, we conclude that this deletion caused the growth hormone insensitivity in this patient.
C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA.
RP COUNTS, DR (reprint author), UNIV MARYLAND, DEPT PEDIAT,DIV PEDIAT ENDOCRINOL,22 S GREENE ST, ROOM N5E13, BOX 264, BALTIMORE, MD 21201 USA.
NR 10
TC 7
Z9 7
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 JUN
PY 1995
VL 80
IS 6
BP 1978
EP 1981
DI 10.1210/jc.80.6.1978
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA RC751
UT WOS:A1995RC75100039
PM 7775649
ER

PT J
AU BAMBERGER, CM
   BAMBERGER, AM
   DECASTRO, M
   CHROUSOS, GP
AF BAMBERGER, CM
   BAMBERGER, AM
   DECASTRO, M
   CHROUSOS, GP
TI GLUCOCORTICOID RECEPTOR-BETA, A POTENTIAL ENDOGENOUS INHIBITOR OF
   GLUCOCORTICOID ACTION IN HUMANS
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE GLUCOCORTICOIDS; GLUCOCORTICOID RECEPTORS; REPORTER GENES;
   POLYACRYLAMIDE GEL ELECTROPHORESIS; POLYMERASE CHAIN REACTION
ID STEROID-HORMONE RECEPTORS; THYROID-HORMONE; DNA-BINDING; RESISTANCE;
   PROTEINS; VARIANT; GENES; TRANSCRIPTION; EXPRESSION; MEDIATE
AB Alternative splicing of the human glucocorticoid receptor (hGR) pre-mRNA generates two highly homologous isoforms, termed hGR alpha and hGR beta. hGR alpha is a ligand-activated transcription factor which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element (GRE) DNA sequences, In contrast, hGR beta does not bind glucocorticoids and is transcriptionally inactive, We demonstrate here that hGR beta is able to inhibit the effects of hormone-activated hGR alpha on a glucocorticoid-responsive reporter gene in a concentration-dependent manner. [H-3]-Dexamethasone binding studies indicate that hGR beta does not alter the affinity of hGR alpha for its hormonal ligand, The presence of hGR beta in nuclear extracts and its ability to bind to a radiolabeled GRE oligonucleotide suggest that its inhibitory effect may be due to competition for GRE target sites, Reverse transcription-PCR analysis shows expression of hGR beta mRNA in multiple human tissues, These results indicate that hGR beta may be a physiologically and pathophysiologically relevant endogenous inhibitor of glucocorticoid action, which may participate in defining the sensitivity of target tissues to glucocorticoids, They also underline the importance of distinguishing between the two receptor isoforms in all future studies of hGR function and the need to revisit old data,
C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892.
   NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892.
RI Castro, Margaret/A-4918-2009
NR 41
TC 437
Z9 479
U1 0
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 222 E 70TH STREET, NEW YORK, NY 10021
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 1995
VL 95
IS 6
BP 2435
EP 2441
DI 10.1172/JCI117943
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA RB212
UT WOS:A1995RB21200006
PM 7769088
ER

PT J
AU GORDON, CT
   COTELINGAM, GM
   STAGER, S
   LUDLOW, CL
   HAMBURGER, SD
   RAPOPORT, JL
AF GORDON, CT
   COTELINGAM, GM
   STAGER, S
   LUDLOW, CL
   HAMBURGER, SD
   RAPOPORT, JL
TI A DOUBLE-BLIND COMPARISON OF CLOMIPRAMINE AND DESIPRAMINE IN THE
   TREATMENT OF DEVELOPMENTAL STUTTERING
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT DISORDER; TOURETTE
   SYNDROME
AB Background:  Clomipramine, a serotonin reuptake blocker that has been shown to be effective in treating obsessive-compulsive disorder and other unwanted repetitive, ritualized behaviors, was hypothesized to be superior to desipramine, a tricyclic antidepressant with selective noradrenergic effects, for developmental stuttering.
   Method:  Seventeen psychiatrically normal subjects, aged 14-61 years, with developmental stuttering completed a 10-week double-blind crossover trial of clomipramine and desipramine after a 2-week single-blind placebo phase.
   Results:  Clomipramine was superior to desipramine (two-tailed, p < .05) for 5 of 10 self-report ratings including stuttering severity on two scales, degree of preoccupation with stuttering and resistance to stuttering on a visual analog scale, and ''expectancy'' of stuttering on the Perceptions of Stuttering Inventory.
   Conclusion:  Clomipramine may be clinically useful for some patients with developmental stuttering.  Biological links between developmental stuttering and other repetitive motor patterns that are selectively responsive to serotonergic agents should be explored.
C1 NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892.
   NATL INST DEAFNESS & OTHER COMMUN DISORDERS,BETHESDA,MD.
OI Stager, Sheila/0000-0002-4294-2114; Ludlow, Christy/0000-0002-2015-6171
NR 16
TC 16
Z9 16
U1 0
U2 2
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUN
PY 1995
VL 56
IS 6
BP 238
EP 242
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA RD447
UT WOS:A1995RD44700003
PM 7775365
ER

PT J
AU ASCHELE, C
   GUGLIELMI, A
   MORI, A
   TIXI, L
   BOLLI, E
   CIFERRI, E
   FAZIO, S
   MUNICINO, O
   SOBRERO, A
AF ASCHELE, C
   GUGLIELMI, A
   MORI, A
   TIXI, L
   BOLLI, E
   CIFERRI, E
   FAZIO, S
   MUNICINO, O
   SOBRERO, A
TI THE 2 SIDES OF 5-FLUOROURACIL - BOLUS AND CONTINUOUS-INFUSION
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
C1 NATL CANC INST,DEPT MED ONCOL,GENOA,ITALY.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU APSIT ASSOC PROM STUD IMMUNOL TUMOR
PI ROME
PA VIALE REGINA ELENA 291, 00161 ROME, ITALY
SN 0392-9078
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD JUN
PY 1995
VL 14
IS 2
SU S
BP 53
EP 59
PG 7
WC Oncology
SC Oncology
GA RJ516
UT WOS:A1995RJ51600008
ER

PT J
AU KARUPIAH, G
   HARRIS, N
AF KARUPIAH, G
   HARRIS, N
TI INHIBITION OF VIRAL REPLICATION BY NITRIC-OXIDE AND ITS REVERSAL BY
   FERROUS SULFATE AND TRICARBOXYLIC-ACID CYCLE METABOLITES
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ACTIVATED MACROPHAGES; INTERFERON-GAMMA; MURINE MACROPHAGES;
   RIBONUCLEOTIDE REDUCTASE; NEOPLASTIC-CELLS; TUMOR-CELLS; L-ARGININE;
   INFECTION; MICE; SYNTHASE
AB IFN-gamma-induced nitric oxide (NO) in the murine macrophage-derived cell line RAW 264.7 was previously shown to inhibit replication of the poxviruses ectromelia and vaccinia (VV) and HSV-1. In the current study we demonstrate that murine macrophages activated as a consequence of VV infection express inducible nitric oxide synthase. These activated macrophages were resistant to infection with VV and efficiently blocked the replication of VV and HSV-1 in infected bystander cells of epithelial and fibroblast origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and reversible by the NOS inhibitor N-pi-monomethyl-L-arginine. NO-mediated inhibition of VV replication was studied by treatment of virus-infected human 293 cells with the NO donor S-nitroso-N-acetyl-penicillamine. Using a W-specific DNA probe, antibodies specific for temporally expressed viral proteins, and transmission electron microscopy, we have shown that NO inhibited viral late gene protein synthesis, DNA replication, and virus particle formation, but not expression of the early proteins that were analyzed. Putative enzymatic targets of NO were identified by reversing the NO-mediated inhibition of VV replication in the 293 cells with exogenous ferrous sulfate and L-cysteine. Reversal of inhibition may derive from the capacity of these reagents to protect or regenerate nonheme iron or thiol groups, respectively, which are essential for the catalytic activities of enzymes susceptible to inactivation by NO.
C1 NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA.
RI Karupiah, Gunasegaran/J-4707-2013
NR 40
TC 88
Z9 88
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUN 1
PY 1995
VL 181
IS 6
BP 2171
EP 2179
DI 10.1084/jem.181.6.2171
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA RA605
UT WOS:A1995RA60500025
PM 7539042
ER

PT J
AU MUSZYNSKI, KW
   RUSCETTI, FW
   HEIDECKER, G
   RAPP, U
   TROPPMAIR, J
   GOOYA, JM
   KELLER, JR
AF MUSZYNSKI, KW
   RUSCETTI, FW
   HEIDECKER, G
   RAPP, U
   TROPPMAIR, J
   GOOYA, JM
   KELLER, JR
TI RAF-1 PROTEIN IS REQUIRED FOR GROWTH FACTOR-INDUCED PROLIFERATION OF
   HEMATOPOIETIC-CELLS
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; IL-6 SIGNAL TRANSDUCER; KINASE-ACTIVITY; MAP
   KINASE; PROGENITOR CELLS; FACTOR RECEPTOR; BONE-MARROW; GM-CSF; C-RAF;
   V-RAF
AB Raf-1 is a 74-kD serine/threonine kinase located in the cell cytoplasm that is activated by phosphorylation in cells stimulated with a variety of mitogens and growth factors, including hematopoietic growth factors. Using c-raf antisense oligonucleotides to block Raf-1 expression, we have established that Raf-1 is required for hematopoietic growth factor-induced proliferation of murine cell lines stimulated by growth factors whose receptors are members of several different structural classes: (a) the hematopoietin receptor family, including interleukin (IL)-2, IL-3, IL-4, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor (GM-CSF), and erythropoietin; (b) the tyrosine kinase receptor class, including Steel factor and CSF-1; and (c) IL-6, leukemia inhibitory factor, and oncostatin M, whose receptors include the gp130 receptor subunit. Although results of previous experiments had suggested that IL-4 does not phosphorylate or activate the Raf-1 kinase, c-raf antisense oligonucleotides inhibited IL-4-induced proliferation of both myeloid and T cell lines, and IL-4 activated Raf-1 kinase activity in an IL-4-dependent myeloid cell line. In colony assays, c-raf antisense oligonucleotides completely inhibited colony formation of unseparated normal murine bone marrow cells stimulated with either IL-3 or CSF-1 and partially inhibited cells stimulated with GM-CSF. In addition, c-raf antisense oligonucleotides completely inhibited both IL-3- and GM-CSF-induced colony formation of CD34(+) purified human progenitors stimulated with these same growth factors. Thus, Raf-1 is required for growth factor-induced proliferation of leukemic murine progenitor cell lines and normal murine and human bone marrow-derived progenitor cells regardless of the growth factor used to stimulate cell growth.
C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702.
RP MUSZYNSKI, KW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA.
NR 52
TC 52
Z9 52
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 JUN 1
PY 1995
VL 181
IS 6
BP 2189
EP 2199
DI 10.1084/jem.181.6.2189
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA RA605
UT WOS:A1995RA60500027
PM 7539043
ER

PT J
AU KIRK, KL
AF KIRK, KL
TI CHEMISTRY AND PHARMACOLOGY OF RING-FLUORINATED CATECHOLAMINES
SO JOURNAL OF FLUORINE CHEMISTRY
LA English
DT Article; Proceedings Paper
CT International Conference on Fluorine Chemistry 94 Kyoto
CY JUL 27-30, 1994
CL KYOTO, JAPAN
SP Japan Soc Promot Sci, 155th Comm Fluorine Chem, Chem Soc Japan, Electrochem Soc Japan, Pharm Soc Japan, Soc Synth Organ Chem
DE RING FLUORINATED CATECHOLAMINES; CHEMICAL NEUROTRANSMITTERS; AGONISTS;
   PHARMACOLOGICAL AGENTS; SYNTHESIS; PRODRUGS
ID ADRENERGIC ACTIVITIES; AFFINITY; SUBSTITUTION; SPECIFICITY; IONIZATION;
   RECEPTORS; AGONISTS; AMINES
AB Naturally-occurring catecholamines have important and diverse physiological roles, including serving as chemical neurotransmitters. The responses of catecholamines functioning as adrenergic agonists can be profoundly altered by ring fluorination, depending on the site of fluorination and the nature of the agonist. Such ring-fluorinated catecholamines serve as selective pharmacological agents, and can be used to probe enzyme and receptor mechanisms. Studies to understand the molecular mechanism by which fluorine alters ligand-agonist binding have included the synthesis of several new fluorinated agonist analogues, and now have been extended to probing selective interactions with cloned receptors. New catecholamino-acids have been synthesized that are designed to be prodrugs for selective in vivo response.
RP KIRK, KL (reprint author), NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA.
NR 32
TC 18
Z9 18
U1 0
U2 2
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0022-1139
J9 J FLUORINE CHEM
JI J. Fluor. Chem.
PD JUN
PY 1995
VL 72
IS 2
BP 261
EP 266
DI 10.1016/0022-1139(94)00417-E
PG 6
WC Chemistry, Inorganic & Nuclear; Chemistry, Organic
SC Chemistry
GA RD582
UT WOS:A1995RD58200017
ER

PT J
AU PARKER, JC
   DUNHAM, PB
   MINTON, AP
AF PARKER, JC
   DUNHAM, PB
   MINTON, AP
TI EFFECTS OF IONIC-STRENGTH ON THE REGULATION OF NA/H EXCHANGE AND K-CL
   COTRANSPORT IN DOG RED-BLOOD-CELLS
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID SEDIMENTATION EQUILIBRIUM; CONCENTRATED-SOLUTIONS; COORDINATED
   REGULATION; VOLUME; TRANSPORT; ACTIVATION; PROTEINS; CONSEQUENCES;
   METABOLISM; HEMOGLOBIN
AB Dog red cell membranes contain two distinct volume-sensitive transporters: swelling-activated K-CI cotransport and shrinkage-activated Na/H exchange. Cells were prepared with intracellular salt concentration and weight percentage of cell water (%cw) varied independently by transient permeabilization of the cell membrane to cations. The dependence of transporter-mediated Na and K influxes upon %cw and upon extracellular salt concentration (c(ext)) was measured in cells so prepared. It was found that the critical value of %cw at which transporters are activated, called the set point, is similar for the two transporters, and that the set points for the two transporters decrease similarly with increasing extracellular salt concentration. These findings suggest a common mechanism of regulation of these two transporters.
   Cellular Na, K, and Cl concentrations were measured as functions of %cw and c(ext). Using these data together with data from the literature for other solute concentrations, empirical expressions were developed to describe the dependence of the intracellular concentrations of all significant small molecule electrolytes, and therefore the intracellular ionic strength, upon %cw and c(ext).
   A mechanistic model for the dependence of the set point of an individual transporter upon intracellular ionic strength is proposed. According to this model, the set point represents a critical extent of association between the transporter and a postulated soluble regulatory protein, called regulator. Model functions are presented for the calculation of the thermodynamic activity of regulator, and hence extent of regulator-transporter association, as a function of total intracellular protein concentration (or %cw) and ionic strength. The experimentally observed dependence of set point %cw on c(ext) are simulated using these functions and the empirical expressions described above, together with reasonable but not uniquely determined values of model parameters.
C1 SYRACUSE UNIV,DEPT BIOL,BIOL RES LAB,SYRACUSE,NY 13244.
   UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599.
   NIDDK,BIOCHEM PHARMACOL LAB,PHYS BIOCHEM SECT,BETHESDA,MD 20892.
FU NIDDK NIH HHS [DK-33640, DK-11356]
NR 37
TC 31
Z9 32
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 222 E 70TH STREET, NEW YORK, NY 10021
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUN
PY 1995
VL 105
IS 6
BP 677
EP 699
DI 10.1085/jgp.105.6.677
PG 23
WC Physiology
SC Physiology
GA RH078
UT WOS:A1995RH07800001
PM 7561739
ER

PT J
AU LAU, JYN
   SALLIE, R
   FANG, JWS
   YARBOUGH, PO
   REYES, GR
   PORTMANN, BC
   MIELIVERGANI, G
   WILLIAMS, R
AF LAU, JYN
   SALLIE, R
   FANG, JWS
   YARBOUGH, PO
   REYES, GR
   PORTMANN, BC
   MIELIVERGANI, G
   WILLIAMS, R
TI DETECTION OF HEPATITIS-E VIRUS GENOME AND GENE-PRODUCTS IN 2 PATIENTS
   WITH FULMINANT HEPATITIS-E
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE DETECTION; FULMINANT HEPATITIS; HEPATITIS E VIRUS; HEPATITIS E VIRUS
   ANTIGENS; HEPATITIS E VIRUS RNA; PATHOGENESIS
ID NON-B HEPATITIS; LIVER-TISSUE; NON-A; EPITOPES
AB Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards hepatitis E virus ORF1) and immunohistochemistry (against hepatitis E virus ORF2 and ORF3) were applied to detect hepatitis E virus genome and gene product in the liver tissue of two patients with fulminant hepatitis E seropositive for hepatitis E virus RNA, Both hepatitis E virus RNA and hepatitis E virus antigens were detected exclusively in the cytoplasm of hepatocytes and not detected in other cell types, In both patients, more than 50% of the hepatocytes were positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of which showed degenerative changes, This is consistent with the histological appearance of marked loss of hepatocytes with acinar collapse, Interestingly, denaturation of the RNA before in situ hybridization was found to enhance hepatitis E virus RNA detection, We conclude that: (1) hepatitis E virus RNA and hepatitis E virus antigens can be demonstrated in the liver in hepatitis E virus-related fulminant hepatitic failure, (2) hepatitis E virus is hepatocyte-tropic within the liver, (3) cytoplasmic localization of hepatitis E virus RNA and hepatitis E virus antigens is consistent with cytoplasmic replication, and (4) the presence of degenerative changes in hepatitis E virus positive cells, together with the histological appearance of hepatocyte loss in the absence of significant inflammatory infiltrate, suggests that hepatitis E virus-related fulminant hepatitic failure is mediated by a cytopathic mechanism.
C1 NIDDK,LIVER UNIT,BETHESDA,MD.
   BIOTECH RESOURCES INC,SAN ANTONIO,TX.
   UNIV LONDON KINGS COLL,SCH MED & DENT,INST LIVER STUDIES,LONDON WC2R 2LS,ENGLAND.
   UNIV LONDON KINGS COLL,SCH MED & DENT,DEPT CHILD HLTH,LONDON WC2R 2LS,ENGLAND.
RP LAU, JYN (reprint author), UNIV FLORIDA,DEPT MED,DIV GASTROENTEROL HEPATOL & NUTR,HEPATOBILIARY DIS SECT,POB 100214 JHMHC,GAINESVILLE,FL 32610, USA.
NR 17
TC 19
Z9 20
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 JUN
PY 1995
VL 22
IS 6
BP 605
EP 610
DI 10.1016/0168-8278(95)80215-0
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA RL115
UT WOS:A1995RL11500001
PM 7560853
ER

PT J
AU CHANOCK, SJ
   PIZZO, PA
AF CHANOCK, SJ
   PIZZO, PA
TI INFECTION PREVENTION STRATEGIES FOR CHILDREN WITH CANCER AND AIDS -
   CONTRASTING DILEMMAS
SO JOURNAL OF HOSPITAL INFECTION
LA English
DT Article; Proceedings Paper
CT 3rd International Conference of the Hospital-Infection-Society
CY SEP 04-08, 1994
CL LONDON, ENGLAND
SP Hosp Infect Soc
DE HIV; NEUTROPENIA; IMMUNODEFICIENCY; HOST DEFENSE; CANCER
ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; PROPHYLACTIC
   TRIMETHOPRIM-SULFAMETHOXAZOLE; ACUTE NONLYMPHOCYTIC LEUKEMIA;
   BONE-MARROW TRANSPLANTATION; ANTI-MICROBIAL MODULATION; INTENSIVE-CARE
   UNITS; BACTERIAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; CONTROLLED
   TRIAL
AB Infectious complications represent significant challenges for children with cancer and those infected with HIV. Although both have similarities in the disease- and treatment-related alterations in host defences, there are significant differences that can have an impact on the approach to treatment and prevention of the dominant infectious complications. An important difference is that children with cancer readily recover from neutropenia. Thus, the immune deficits are interspersed with intervals of immunological recovery. On the other hand, children with HIV infection do not appreciably recover from the progressive, immunological changes associated with the underlying HIV infection. The loss of cellular and humoral immunity is generally not reversible, and thus the risk of infection only increases over time. Bacteria constitute the predominant pathogen for paediatric cancer patients but invasive mycoses, viruses and parasitic infections are emerging as important pathogens. In paediatric cancer patients, strategies have been directed at altering or suppressing the endogenous colonization patterns of pathogenic bacteria. The success of this approach has been limited and at the expense of selecting for antibiotic-resistant bacterial infections. Children with HIV infection are at risk of developing a wide spectrum of pathogens. Strategies for infection prevention in the HIV setting have been directed at specific organisms, generally using more specific antimicrobial agents and with greater success.
RP CHANOCK, SJ (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA.
NR 68
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX
SN 0195-6701
J9 J HOSP INFECT
JI J. Hosp. Infect.
PD JUN
PY 1995
VL 30
SU S
BP 197
EP 208
DI 10.1016/0195-6701(95)90020-9
PG 12
WC Infectious Diseases
SC Infectious Diseases
GA RH518
UT WOS:A1995RH51800021
PM 7560951
ER

PT J
AU KENNY, JJ
   STALL, AM
   FISCHER, RT
   DERBY, E
   YANG, MCW
   TUCKER, PW
   LONGO, DL
AF KENNY, JJ
   STALL, AM
   FISCHER, RT
   DERBY, E
   YANG, MCW
   TUCKER, PW
   LONGO, DL
TI IG-GAMMA-2B TRANSGENES PROMOTE B-CELL DEVELOPMENT BUT ALTERNATE
   DEVELOPMENTAL PATHWAYS APPEAR TO FUNCTION IN DIFFERENT TRANSGENIC LINES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HEAVY-CHAIN GENE; MONOCLONAL-ANTIBODIES; ALLELIC EXCLUSION;
   IMMUNOGLOBULIN GENES; TARGETED DISRUPTION; MEMBRANE EXON; MU-GENES;
   MICE; EXPRESSION; MOUSE
AB Analysis of B cell development in three strains of gamma 2b transgenic mice shows that the gamma 2b H chain can replace the mu H chain in promoting B cell differentiation, The 348C line produces 90% gamma 2b-only B cells and 10% B cells, which co-express gamma 2b and endogenous sIgM and sIgD. These IgG2b(+) B cells develop into mature, recirculating CD23(+) B cells. The 343-1 and gamma 2b-T15 transgenic mice produce sIgM(high):sIgD(low):CD23(-) B cells that generally co-express the gamma 2b transgene-encoded H chain. Such B cells are either developmentally arrested immature B cells or arise from B-1 (CD5) progenitors. The gamma 2b-T15 mice can produce gamma 2b-only CD23(+) B cells following inactivation of the endogenous mu locus, whereas 343-1 mice fail to develop B cells. Thus, gamma 2b H chains: 1) can act alone to promote the development of mature B cells, 2) synergize with mu H chains for allelic exclusion, and 3) vary in their influence on B cell development in different transgenic mouse strains.
C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702.
   COLUMBIA UNIV,COLL PHYS & SURG,DEPT MICROBIOL & IMMUNOL,NEW YORK,NY 10032.
   UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235.
RP KENNY, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA.
FU NIAID NIH HHS [AI-18016]
NR 41
TC 20
Z9 20
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 1995
VL 154
IS 11
BP 5694
EP 5705
PG 12
WC Immunology
SC Immunology
GA RB197
UT WOS:A1995RB19700010
PM 7751621
ER

PT J
AU SARIN, A
   NAKAJIMA, H
   HENKART, PA
AF SARIN, A
   NAKAJIMA, H
   HENKART, PA
TI A PROTEASE-DEPENDENT TCR-INDUCED DEATH PATHWAY IN MATURE LYMPHOCYTES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN MEDULLARY THYMOCYTES; PROGRAMMED CELL-DEATH; PERIPHERAL T-CELLS;
   DNA FRAGMENTATION; CYTO-TOXICITY; GENE CED-3; APOPTOSIS; ANTIGEN;
   INTERLEUKIN-2; INVOLVEMENT
AB Several cysteine and serine protease inhibitors previously shown to block TCR-induced death of 2B4 T hybridoma cells were tested for their ability to block various T lymphocyte apoptotic death systems. TCR-induced death of both peripheral CD4(+) and CD8(+) T cell blasts was inhibited similarly to the hybridoma, but cell death in these cells induced by anti-Fas, gamma-irradiation, etoposide, or extracellular ATP was not blocked. For T cell lines, cell death induced by CTL or by IL-2 withdrawal was also not inhibited. TCR-induced death oi immature CD4(-)8(+) thymocytes triggered by culture on immobilized anti-CD3 was not blocked by these protease inhibitors, whereas similar death induced in the resting CD4(+)8(-) thymocyte subset under these conditions was inhibited similarly to the T cell blasts. TCR-induced proliferation of the latter subset was modest in the absence of oxogeneous IL-2, but was enhanced two- to fourfold by the protease inhibitors. These results show that a protease-dependent death pathway can be triggered by the TCR in mature T cells; similar protease-dependent steps are not common to the TCR-triggered activation pathway or other apoptotic death pathways in these cells.
C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892.
NR 34
TC 38
Z9 38
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 1995
VL 154
IS 11
BP 5806
EP 5812
PG 7
WC Immunology
SC Immunology
GA RB197
UT WOS:A1995RB19700021
PM 7751630
ER

PT J
AU ROBBINS, PF
   ELGAMIL, M
   LI, YF
   TOPALIAN, SL
   RIVOLTINI, L
   SAKAGUCHI, K
   APPELLA, E
   KAWAKAMI, Y
   ROSENBERG, SA
AF ROBBINS, PF
   ELGAMIL, M
   LI, YF
   TOPALIAN, SL
   RIVOLTINI, L
   SAKAGUCHI, K
   APPELLA, E
   KAWAKAMI, Y
   ROSENBERG, SA
TI CLONING OF A NEW GENE ENCODING AN ANTIGEN RECOGNIZED BY
   MELANOMA-SPECIFIC HLA-A24-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CYTOLYTIC T-LYMPHOCYTES; METASTATIC MELANOMA; IMMUNOTHERAPY; RELEASE
AB The role of tumor-specific T cells in mediating the regression of metastatic melanoma has been suggested by the clinical response of patients to treatment with tumor-infiltrating lymphocytes (TIL). A number of Ags recognized by class I-restricted melanoma-specific T cells have recently been isolated, raising the hope that this will lead to the development of improved therapies. In this study, we report the cloning of a tumor Ag recognized by T cells from melanoma patient 888. Previously, we reported that TIL 888, grown from the tumor of this patient, recognized tyrosinase in an HLA-A24-restricted fashion. This line, when infused into the autologous patient, resulted in complete regression of multiple metastases. Three years later, a second TIL line, TIL 1290, was isolated from a recurrent pelvic tumor. Infusion of a mixture of TIL 888 and TIL 1290 cell lines into the patient resulted in complete regression of a residual abdominal mass and the patient remains disease-free 2 yr later. The TIL 1290 cell line, which recognized melanoma in an HLA-A24-restricted manner, failed to recognize tyrosinase. TIL 1290 was then used to screen an 888 melanoma cDNA library, and an Ag was isolated that did not correspond to any found in sequence databases. This gene, termed p15, was found to be expressed in a variety of normal tissues, and a peptide epitope recognized by TIL 1290 was found to represent the product of an nonmutated gene. Screening of additional cDNA pools resulted in the isolation of a second clone which stimulated TIL 1290. This clone also appeared to represent a transcript of the p15 gene, indicating that this gene may encode the predominant Ag recognized by TIL 1290.
C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892.
RP ROBBINS, PF (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,10 CTR DR MSC 1502,BETHESDA,MD 20892, USA.
RI Kawakami, Yutaka /E-7429-2013; 
OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini,
   Licia/0000-0002-2409-6225
NR 27
TC 129
Z9 131
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 1995
VL 154
IS 11
BP 5944
EP 5950
PG 7
WC Immunology
SC Immunology
GA RB197
UT WOS:A1995RB19700036
PM 7751637
ER

PT J
AU UDHAYAKUMAR, V
   ANYONA, D
   KARIUKI, S
   SHI, YP
   BLOLAND, PB
   BRANCH, OH
   WEISS, W
   NAHLEN, BL
   KASLOW, DC
   LAL, AA
AF UDHAYAKUMAR, V
   ANYONA, D
   KARIUKI, S
   SHI, YP
   BLOLAND, PB
   BRANCH, OH
   WEISS, W
   NAHLEN, BL
   KASLOW, DC
   LAL, AA
TI IDENTIFICATION OF T-CELL AND B-CELL EPITOPES RECOGNIZED BY HUMANS IN THE
   C-TERMINAL 42-KDA DOMAIN OF THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE
   PROTEIN (MSP)-1
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INHIBIT PARASITE GROWTH; AOTUS MONKEYS; CIRCUMSPOROZOITE PROTEIN;
   ANTIGEN GENE; BLOOD STAGES; MALARIA; ANTIBODIES; RECOMBINANT;
   IMMUNIZATION; IMMUNITY
AB The 42-kDa, C-terminal region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a putative malaria vaccine candidate Ag. Nine synthetic peptides corresponding to predicted T cell sites of MSP-1 in blocks 15 and 16 and eight overlapping peptides representing the conserved block 17 were used to identify naturally immunogenic epitopes. These peptides were tested for their ability to induce proliferation of PBMC from residents in western Kenya, where malaria transmission is holoendemic. Six peptides (PL145, PL146, PL147, PL148, PL149, and PL150) from blocks 15 and 16 induced a positive proliferative response in >30% of the individuals tested, and three peptides (PL151, PL152, and PL153) induced a proliferative response in <25% of the donors. Among these peptides, PL146 was from the highly conserved region, PL150 was from a polymorphic region, and all other peptides were from a dimorphic region of blocks 15 and 16. In block 17, only three peptides, PL99, PL100, and PL103, induced proliferation in 30 to 37% of the volunteers. The rest of the peptides induced a proliferative response in approximately 13 to 25% of the donors. The plasma from these donors widely reacted with different allelic forms of 19-kDa recombinant proteins representing block 17 and recognized at least two linear B epitopes, PL104 and PL97. In summary, this study revealed that a majority of immunodominant T and B epitopes are localized in the conserved or dimorphic regions that are nonpolymorphic in the 42-kDa protein of MSP-1. This study suggests that incorporation of T epitopes from the dimorphic blocks 15 and 16 in a vaccine construct may be useful to ensure Ag-specific memory responses.
C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV PARASIT DIS,ATLANTA,GA 30341.
   KENYA GOVT MED RES CTR,VECTOR BIOL & CONTROL RES CTR,KISSIAN,KENYA.
   NIAID,MALARIA RES LAB,BETHESDA,MD 20892.
RP UDHAYAKUMAR, V (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,IMMUNOL BRANCH,MAIL STOP F-12,4770 BUFORD HWY,ATLANTA,GA 30341, USA.
NR 28
TC 96
Z9 96
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 1995
VL 154
IS 11
BP 6022
EP 6030
PG 9
WC Immunology
SC Immunology
GA RB197
UT WOS:A1995RB19700045
PM 7538540
ER

PT J
AU PELFREY, CM
   TRANQUILL, LR
   BOEHME, SA
   MCFARLAND, HF
   LENARDO, MJ
AF PELFREY, CM
   TRANQUILL, LR
   BOEHME, SA
   MCFARLAND, HF
   LENARDO, MJ
TI 2 MECHANISMS OF ANTIGEN-SPECIFIC APOPTOSIS OF MYELIN BASIC-PROTEIN
   (MBP)-SPECIFIC T-LYMPHOCYTES DERIVED FROM MULTIPLE-SCLEROSIS PATIENTS
   AND NORMAL INDIVIDUALS
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CELL-DEATH; DNA FRAGMENTATION; FAS; METHYLPREDNISOLONE; ACTIVATION;
   EXPRESSION; RESISTANCE; INTERLEUKIN-2; RESTRICTION; THYMOCYTES
AB Several stimuli induce mature T cells to undergo apoptosis or programmed cell death (PCD) including specific Ag. We have demonstrated previously that Ag induces the death of encephalitogenic T cells in vitro and deletion in vivo, leading to amelioration of autoimmune encephalomyelitis. We have now examined whether activated, myelin basic protein (MBP)-specific human T cells may be eliminated by Ag-induced PCD. We demonstrate that activated MBP-specific T cell lines (TCL) undergo the classic nuclear morphologic changes and DNA fragmentation characteristic of apoptosis when given a TCR challenge. We found evidence that two mechanisms led to apoptosis: a propriocidal mechanism that was highly Ag-specific and dependent on the dose of exogenously added rlL-2, and a cytolytic mechanism in which MBP-specific TCL lysed B cell targets and engaged in considerable ''fratricidal'' cytolysis of other MBP-specific T cells. These two pathways leading to MBP-specific apoptotic death could be distinguished by their glucocorticoid sensitivity. Glucocorticoid treatment significantly blocked MBP-induced propriocidal apoptosis but had no effect on T cell cytolysis of B cell targets. Although it has been proposed that autoimmune disease could result from the failure of normal deletional mechanisms, this preliminary survey of MBP-reactive mature TCL from multiple sclerosis patients revealed that such cells are highly susceptible to TCR-induced PCD and comparable with TCL from normal subjects. Thus, therapeutic strategies based on Ag-induced PCD of T lymphocytes may be feasible in man.
C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892.
   NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892.
OI Pelfrey, Clara/0000-0002-6108-7555
NR 55
TC 50
Z9 50
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 1995
VL 154
IS 11
BP 6191
EP 6202
PG 12
WC Immunology
SC Immunology
GA RB197
UT WOS:A1995RB19700063
PM 7538545
ER

PT J
AU ROBBINS, JB
   SCHNEERSON, R
   SZU, SC
AF ROBBINS, JB
   SCHNEERSON, R
   SZU, SC
TI PERSPECTIVE - HYPOTHESIS - SERUM IGG ANTIBODY IS SUFFICIENT TO CONFER
   PROTECTION AGAINST INFECTIOUS-DISEASES BY INACTIVATING THE INOCULUM
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Review
ID INFLUENZAE TYPE-B; POLYSACCHARIDE IMMUNE GLOBULIN; VI-CAPSULAR
   POLYSACCHARIDE; O-SPECIFIC POLYSACCHARIDE; HIGH-RISK INFANTS;
   ESCHERICHIA-COLI; GROUP-A; BORDETELLA-PERTUSSIS; VACCINE DEVELOPMENT;
   CONJUGATE VACCINE
AB The theory proposed is that a critical level of specific serum IgG is sufficient to confer protection against infectious diseases by inactivating the inoculum of the pathogen. This theory relies heavily on evaluation of licensed vaccines and includes the following: Measurement of serum antibodies only reliably predicts the efficacy of vaccines, according to regulatory agencies. Serum IgG antibodies alone account for the protection conferred by passive immunization, ''Herd'' immunity conferred by vaccines on viral and bacterial diseases is best explained by serum antibodies that inactivate the inoculum on mucosal surfaces, thus reducing the pathogen's transmission. Once the disease is manifest, serum antibodies induced by active immunization will neither relieve symptoms nor eliminate the pathogen; specific IgG must be present when the host encounters the pathogen in order to confer protective immunity. Information about the initial pathogen-host contact is vital, whereas knowledge of the symptomatology of the disease may not be essential for vaccine development.
RP ROBBINS, JB (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 6,ROOM 145,BETHESDA,MD 20892, USA.
NR 171
TC 248
Z9 258
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 JUN
PY 1995
VL 171
IS 6
BP 1387
EP 1398
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA RB298
UT WOS:A1995RB29800001
PM 7769272
ER

PT J
AU PLUDA, JM
   COOLEY, TP
   MONTANER, JSG
   SHAY, LE
   REINHALTER, NE
   WARTHAN, SN
   RUEDY, J
   HIRST, HM
   VICARY, CA
   QUINN, JB
   YUEN, GJ
   WAINBERG, MA
   RUBIN, M
   YARCHOAN, R
AF PLUDA, JM
   COOLEY, TP
   MONTANER, JSG
   SHAY, LE
   REINHALTER, NE
   WARTHAN, SN
   RUEDY, J
   HIRST, HM
   VICARY, CA
   QUINN, JB
   YUEN, GJ
   WAINBERG, MA
   RUBIN, M
   YARCHOAN, R
TI A PHASE I/II STUDY OF 2'-DEOXY-3'-THIACYTIDINE (LAMIVUDINE) IN PATIENTS
   WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID AIDS-RELATED COMPLEX; TYPE-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL
   RESISTANCE; CONTROLLED TRIAL; ZIDOVUDINE AZT; I TRIAL;
   2',3'-DIDEOXYINOSINE DDI; REPLICATION INVITRO; MITOCHONDRIAL-DNA;
   HTLV-III/LAV
AB In a phase I/II trial assessing the toxicity, pharmacokinetics, and activity of the (-) enantiomer of 2'-deoxy-3'-thiacytidine (3TC, lamivudine), 97 patients with AIDS or advanced human immunodeficiency virus (HIV) disease were administered 3TC at 0.5-20.0 mg/kg/day. The cohort's median entry CD4 cell count was 128/mm(3) (range, 7-357). A toxic dose was not reached, although some patients reported mild headache, insomnia, and abdominal symptoms, and there was a general downward trend in neutrophil counts at the highest doses. Although subjective and difficult to interpret, increases in energy and appetite were noted, particularly in patients receiving greater than or equal to 8.0 mg/kg/day. Immunologic and virologic parameters showed evidence of at least transient anti-HIV activity at those higher doses. Although further studies of 3TC as monotherapy are needed, its favorable toxicity profile, evidence of at least transient clinical activity, and results of in vitro resistance experiments support further clinical testing in combination therapy.
C1 NCI,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD.
   BOSTON CITY HOSP,DEPT MED,HEMATOL SECT,BOSTON,MA.
   BOSTON CITY HOSP,DEPT MED,ONCOL SECT,BOSTON,MA.
   BOSTON CITY HOSP,DEPT MED,CLIN AIDS PROGRAM,BOSTON,MA.
   BOSTON UNIV,SCH MED,BOSTON,MA 02118.
   UNIV BRITISH COLUMBIA,ST PAULS HOSP,AIDS RES PROGRAM,VANCOUVER,BC,CANADA.
   UNIV BRITISH COLUMBIA,ST PAULS HOSP,INFECT DIS CLIN,VANCOUVER,BC,CANADA.
   SIR MORTIMER B DAVIS JEWISH HOSP,MONTREAL,PQ,CANADA.
   GLAXO RES INST,RES TRIANGLE PK,NC.
NR 49
TC 85
Z9 85
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN
PY 1995
VL 171
IS 6
BP 1438
EP 1447
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA RB298
UT WOS:A1995RB29800007
PM 7769277
ER

PT J
AU KROHN, MA
   HILLIER, SL
   NUGENT, RP
   COTCH, MF
   CAREY, JC
   GIBBS, RS
   ESCHENBACH, DA
AF KROHN, MA
   HILLIER, SL
   NUGENT, RP
   COTCH, MF
   CAREY, JC
   GIBBS, RS
   ESCHENBACH, DA
TI THE GENITAL FLORA OF WOMEN WITH INTRAAMNIOTIC INFECTION
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID INTRA-AMNIOTIC INFECTION; BACTERIAL VAGINOSIS; CHLAMYDIA-TRACHOMATIS;
   MONOCLONAL-ANTIBODIES; PREMATURE RUPTURE; RISK-FACTORS; GRAM STAIN;
   MEMBRANES; FLUID; ENDOMETRITIS
AB The relationship of genital flora assessed at the end of the second trimester of pregnancy and intraamniotic infection diagnosed by clinical signs and symptoms during labor was evaluated. Women were enrolled at 23-26 weeks of gestation and followed through delivery in the multicenter Vaginal Infections and Prematurity Study (1984-1989). Among the cohort of 11,989 followed through delivery, 286 (2.4%) developed intraamniotic infection. The recovery of Gardnerella vaginalis (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.4-2.4), heavy growth of Bacteroides species (RR = 1.5; 95% CI = 1.1-2.1), and isolation of Mycoplasma hominis (RR = 1.7; 95% CI = 1.3-2.1) from the vagina at the end of the second trimester of pregnancy were associated with an increased risk of intraamniotic infection. Bacterial vaginosis was also associated with intraamniotic infection (RR = 1.5; 95% CI = 1.1-2.2). These findings extend prior studies by showing that prenatal cultures for microorganisms associated with bacterial vaginosis predicted an increased risk of intraamniotic infection.
C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195.
   UNIV WASHINGTON,DEPT OBSTET & GYNECOL,SEATTLE,WA 98195.
   NICHHD,BETHESDA,MD 20892.
   RES TRIANGLE INST,ROCKVILLE,MD.
   UNIV OKLAHOMA,DEPT OBSTET & GYNECOL,OKLAHOMA CITY,OK 73190.
   UNIV COLORADO,HLTH SCI CTR,DEPT OBSTET & GYNECOL,DENVER,CO 80262.
OI Cotch, Mary Frances/0000-0002-2046-4350
FU Intramural NIH HHS [Z99 EY999999]; NICHD NIH HHS [HD-3-2834, HD-3-2832,
   HD-3-2833]
NR 27
TC 81
Z9 81
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN
PY 1995
VL 171
IS 6
BP 1475
EP 1480
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA RB298
UT WOS:A1995RB29800012
PM 7769281
ER

PT J
AU DEZUBE, BJ
   LEDERMAN, MM
   SPRITZLER, JG
   CHAPMAN, B
   KORVICK, JA
   FLEXNER, C
   DANDO, S
   MATTIACCI, MR
   AHLERS, CM
   ZHANG, L
   NOVICK, WJ
   KASDAN, P
   FAHEY, JL
   PARDEE, AB
   CRUMPACKER, CS
AF DEZUBE, BJ
   LEDERMAN, MM
   SPRITZLER, JG
   CHAPMAN, B
   KORVICK, JA
   FLEXNER, C
   DANDO, S
   MATTIACCI, MR
   AHLERS, CM
   ZHANG, L
   NOVICK, WJ
   KASDAN, P
   FAHEY, JL
   PARDEE, AB
   CRUMPACKER, CS
TI HIGH-DOSE PENTOXIFYLLINE IN PATIENTS WITH AIDS - INHIBITION OF
   TUMOR-NECROSIS-FACTOR PRODUCTION
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Note
ID BLOOD MONONUCLEAR-CELLS; REPLICATION; EXPRESSION; DECREASES
AB Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting syndrome. Pentoxifylline decreases TNF production. In cell culture, pentoxifylline decreases HIV replication and gene expression, Since an AIDS Clinical Trial Group study suggested that pentoxifylline (400 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral blood mononuclear cells (PBMC), a second cohort received 800 mg thrice daily for 8 weeks, During treatment, the median decrease in TNF production by PBMC cultured with 0.1 mu g/mL lipopolysaccharide (LPS) was 40%. The median change in TNF mRNA was a 34% decrease, Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zidovudine pharmacokinetics. The most common toxicity was gastrointestinal. Pentoxifylline at dosages of less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA levels and LPS-induced TNF production.
C1 BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215.
   HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA.
   HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA.
   CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH.
   JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD.
   NIAID,DIV AIDS,BETHESDA,MD.
   AIDS CLIN TRIALS GRP,OPERAT OFF,ROCKVILLE,MD.
   HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD,SOMERVILLE,NJ.
   UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA.
RP DEZUBE, BJ (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,330 BROOKLINE AVE,DANA 601,BOSTON,MA 02215, USA.
FU NIAID NIH HHS [AI-95030, AI-27668, AI-62534]
NR 14
TC 49
Z9 49
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN
PY 1995
VL 171
IS 6
BP 1628
EP 1632
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA RB298
UT WOS:A1995RB29800037
PM 7769305
ER

PT J
AU CLEMENS, J
   ALBERT, MJ
   RAO, M
   QADRI, F
   HUDA, S
   KAY, B
   VANLOON, FPL
   SACK, D
   PRADHAN, BA
   SACK, RB
AF CLEMENS, J
   ALBERT, MJ
   RAO, M
   QADRI, F
   HUDA, S
   KAY, B
   VANLOON, FPL
   SACK, D
   PRADHAN, BA
   SACK, RB
TI IMPACT OF INFECTION BY HELICOBACTER-PYLORI ON THE RISK AND SEVERITY OF
   ENDEMIC CHOLERA
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Note
ID CAMPYLOBACTER-PYLORI; FIELD TRIAL; FOLLOW-UP; BANGLADESH; GASTRITIS;
   VACCINES
AB To evaluate the relationship between Helicobacter pylori infection and the subsequent risk and severity of endemic Vit,rio cholerae O1 diarrhea among rural Bangladeshis, 285 children and adults with cholera (cases) and 881 contemporaneously selected community controls were studied. Cases and controls were contrasted for H, pylori infection, as manifested by serum IgG anti-H. pylori antibodies, Although the overall risk of cholera was not significantly increased among H. pylori-infected subjects, the risk of cholera of life-threatening severity was signifi::cantly elevated (relative risk [RR] = 1.61; 95% confidence interval [CI] = 1.07-2.42), A significant increase in the risk of severe cholera was seen in subjects who lacked natural serum vibriocidal antibodies (RR = 2.88; 95% CI = 1.28-6.48) but not in those with such antibodies. Thus, H. pylori infection was associated with a significant increase in the risk of life-threatening cholera, but only among persons lacking natural vibriocidal immunity.
C1 INT CTR DIARRHOEAL DIS RES,DHAKA,BANGLADESH.
   UNIV MARYLAND,CTR BIOTECHNOL,BALTIMORE,MD.
   JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD.
   CTR DIS CONTROL & PREVENT,ATLANTA,GA.
RP CLEMENS, J (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,6100 EXECUT BLVD,ROOM 7B03,ROCKVILLE,MD 20852, USA.
NR 15
TC 54
Z9 54
U1 2
U2 3
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 JUN
PY 1995
VL 171
IS 6
BP 1653
EP 1656
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA RB298
UT WOS:A1995RB29800044
PM 7769312
ER

PT J
AU KRAEMER, KH
AF KRAEMER, KH
TI ARE PEOPLE WHO GET SKIN-CANCER DIFFERENT
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
RP KRAEMER, KH (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA.
FU Intramural NIH HHS [Z01 BC004517-31]
NR 7
TC 1
Z9 1
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 JUN
PY 1995
VL 104
IS 6
BP 887
EP 888
DI 10.1111/1523-1747.ep12606156
PG 2
WC Dermatology
SC Dermatology
GA RC142
UT WOS:A1995RC14200003
PM 7769254
ER

PT J
AU SATO, C
   TSUBOI, R
   SHI, CM
   RUBIN, JS
   OGAWA, H
AF SATO, C
   TSUBOI, R
   SHI, CM
   RUBIN, JS
   OGAWA, H
TI COMPARATIVE-STUDY OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND
   KERATINOCYTE GROWTH-FACTOR EFFECTS ON HUMAN KERATINOCYTES
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID EPITHELIAL-CELLS; MET PROTOONCOGENE; MELANOMA-CELLS; DNA-SYNTHESIS;
   EXPRESSION; MIGRATION; RECEPTOR; MOTILITY; PROLIFERATION; MITOGEN
AB Hepatocyte growth factor/scatter factor (HGF/SF) and keratinocyte growth factor (KGF, also designated FGF-7) are paracrine growth factors secreted by mesenchymal cells and active on a variety of epithelial cell types. In this study, the biologic responses of keratinocytes to these paracrine growth factors were compared. Stimulation of mitogenesis, migration, plasminogen activator (PA) activity, and fibronectin production were examined using human foreskin keratinocytes cultured in serum-free MCDB 153 medium. Although the two factors stimulated a similar level of proliferation when cells were maintained for 5 d in 1.8 mM Ca(++), the peak effect of KGF, observed at 10 ng/ml, was approximately threefold higher than that of HGF/SF when cells were in medium containing 0.15 mM Ca(++). Both agents promoted the migration of cells in few-calcium medium (0.08 mM Ca(++)). However, the magnitude of the response was approximately twofold greater for HGF/SF at 10 ng/ml than KGF at the same concentration. None of the matrix proteins such as type I collagen, type IV collagen, laminin, or fibronectin either stimulated or suppressed HGF/SF- or KGF-stimulated keratinocyte migration. Both factors stimulated PA activity of the cell extracts, especially urokinase-type, with similar potencies. Promoted PA activity was maximal with the addition of 10 ng/ml of either factor. Neither factor increased the production of fibronectin under conditions in which transforming growth factor-beta 1 was active. These results indicate that HGF/SF and KGF, both recognized as paracrine growth factors, elicit distinctive patterns of response by keratinocytes, implying that they have different roles in epidermal physiology.
C1 JUNTENDO UNIV, SCH MED, DEPT DERMATOL, BUNKYO KU, TOKYO 113, JAPAN.
   NATL CANC INST, MOLEC & CELLULAR BIOL LAB, BETHESDA, MD USA.
NR 48
TC 69
Z9 70
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 1995
VL 104
IS 6
BP 958
EP 963
DI 10.1111/1523-1747.ep12606221
PG 6
WC Dermatology
SC Dermatology
GA RC142
UT WOS:A1995RC14200016
PM 7769266
ER

PT J
AU YANCEY, KB
AF YANCEY, KB
TI ADHESION MOLECULES .2. INTERACTIONS OF KERATINOCYTES WITH EPIDERMAL
   BASEMENT-MEMBRANE
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID BULLOUS PEMPHIGOID ANTIGEN; JUNCTIONAL EPIDERMOLYSIS-BULLOSA;
   GESTATIONIS AUTOANTIBODIES RECOGNIZE; HERPES-GESTATIONIS; CELL-ADHESION;
   CHROMOSOMAL ASSIGNMENT; CDNA CLONING; PROTEIN; LAMININ; 230-KD
RP YANCEY, KB (reprint author), NCI, DERMATOL BRANCH, BLDG 10, ROOM 12N238, BETHESDA, MD 20892 USA.
NR 72
TC 47
Z9 47
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 JUN
PY 1995
VL 104
IS 6
BP 1008
EP 1014
DI 10.1111/1523-1747.ep12606244
PG 7
WC Dermatology
SC Dermatology
GA RC142
UT WOS:A1995RC14200025
PM 7769251
ER

PT J
AU VARMUS, HE
AF VARMUS, HE
TI THE JIM INTERVIEW - VARMUS,HAROLD,E., MD - DIRECTOR,
   NATIONAL-INSTITUTES-OF-HEALTH
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Editorial Material
AB On November 19, 1993, the Senate approved the nomination of Harold E. Varmus, MD, as Director of the National Institutes of Health (NIH). Varmus, who received the 1989 Nobel prize in Medicine, brought unquestioned credentials as a scientist to the NIH. Despite his limited background as an administrator, Varmus has received high marks from most observers for improving the morale of NIH staffers and implementing streamlined procedures in the grant review process.
   His tenure has not been free of controversy, however, Many clinical researchers have long felt there is a bias in NIH study sections against patient-oriented research, A recent study sponsored by the Division of Research Grants confirmed the lower success rate of patient-oriented research proposals, but the outcome of these findings remains unclear Faced with mounting political pressure for a balanced budget, and the resultant reduction of funding to many branches of government, Varmus has been a strong voice for non-targeted investigator initiated research.
   Interviewed in his office in Building One on the NIH campus in Bethesda, Maryland Varmus discussed the state of patient oriented research, the evolving role of the NIH in supporting science, and just where the money to pay for it should be found.
RP VARMUS, HE (reprint author), NIH,BLDG 1,BETHESDA,MD 20892, USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086
SN 1081-5589
J9 J INVEST MED
JI J. Investig. Med.
PD JUN
PY 1995
VL 43
IS 3
BP 220
EP 226
PG 7
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA RE173
UT WOS:A1995RE17300002
PM 7614067
ER

PT J
AU LEVINE, SJ
AF LEVINE, SJ
TI BRONCHIAL EPITHELIAL CELL-CYTOKINE INTERACTIONS IN AIRWAY INFLAMMATION
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA;
   INTERLEUKIN-8 GENE-EXPRESSION; RESPIRATORY SYNCYTIAL VIRUS;
   CYSTIC-FIBROSIS; T-CELLS; GM-CSF; EOSINOPHIL CHEMOTAXIS;
   HISTAMINE-RELEASE
RP LEVINE, SJ (reprint author), NIH, WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED, BLDG 10,ROOM 7D43, 10 CTR DR MSC 1662, BETHESDA, MD 20892 USA.
NR 98
TC 143
Z9 145
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD JUN
PY 1995
VL 43
IS 3
BP 241
EP 249
PG 9
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA RE173
UT WOS:A1995RE17300005
PM 7614070
ER

PT J
AU ORTALDO, JR
   WILTROUT, TA
   SAYERS, TJ
   YAGITA, H
   WINKLERPICKETT, RT
AF ORTALDO, JR
   WILTROUT, TA
   SAYERS, TJ
   YAGITA, H
   WINKLERPICKETT, RT
TI CHARACTERIZATION OF A NON-GRANULE ASSOCIATED PORE-FORMING PROTEIN IN
   AGRANULAR LYMPHOCYTES
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE LYMPHOCYTES; MEMBRANE; NK CELLS; PERFORIN
ID NATURAL-KILLER-CELLS; PURIFIED CYTOPLASMIC GRANULES; RAT LGL TUMORS; NK;
   CYTOTOXICITY; ACTIVATION; EXPRESSION; RESPONSES; ANTIBODY; SIGNALS
AB Recently, two populations of small lymphocytes (SL) have exhibited non-major histocompatibility complex (MHC) restricted lysis, Recent studies by numerous laboratories have demonstrated that resting T cells triggered through CD3 and CD28 costimulations can result in immediate, non-MHC restricted killing, Our recent studies with CD3(-), CD56(+) SL demonstrated that although these cells contained no cytoplasmic granules detected with electron microscopy, they mediated potent NK and ADCC activity, In the present study, we have used a Western blotting technique that allows for the detection and quantitation of total cellular levels of pore-forming protein (PEP), We have found that freshly isolated peripheral non-granulated lymphocytes (both CD3(+) and CD3(-)) contain PFP. In addition, CD3(-), CD56(+) SL contain levels of PFP similar to those of the highly granular CD3(-) LGL. In search of non-ganule PFP, we exploited the rat NK (RNK) cell lines as a source of other potential cytotoxic factors, A membrane associated PFP, based on Western blotting, was isolated from rat RNK cells, Unlike PFP isolated from granules, this PFP was active after culture in Ca2+-containing medium. However, the lytic activity isolated from the non-granule PFP of RNK cells was inhibited by monoclonal antibodies to PFP, Collectively, these studies indicate that PFP is present in small agranular lymphocytes (both NK and T cells) and that it is not stored in large cytoplasmic granules, The implication of our results for the acquisition and activation of lytic ability in NK and T cells will be discussed.
C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
   JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN.
RP ORTALDO, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DCT,BRMP,EXPTL IMMUNOL LAB,BLDG 560,RM 31-93,FREDERICK,MD 21701, USA.
RI Sayers, Thomas/G-4859-2015
NR 27
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 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD JUN
PY 1995
VL 57
IS 6
BP 897
EP 903
PG 7
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA RE360
UT WOS:A1995RE36000014
PM 7790773
ER

PT J
AU SCHWARTZ, GN
   KESSLER, SW
   SZABO, JM
   BURRELL, LM
   FRANCIS, ML
AF SCHWARTZ, GN
   KESSLER, SW
   SZABO, JM
   BURRELL, LM
   FRANCIS, ML
TI NEGATIVE REGULATORS MAY MEDIATE SOME OF THE INHIBITORY EFFECTS OF
   HIV-1-INFECTED STROMAL CELL-LAYERS ON ERYTHROPOIESIS AND MYELOPOIESIS IN
   HUMAN BONE-MARROW LONG-TERM CULTURES
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE COLONY FORMING UNITS FOR GRANULOCYTES MACROPHAGES (CFU-GM); BURST
   FORMING UNITS ERYTHROID (BFU-E); BONE MARROW LONG-TERM CULTURES (LTC);
   HIV-1(ADA); INTERFERON-ALPHA (IFN-ALPHA); TUMOR NECROSIS FACTOR ALPHA
   (TNF-ALPHA); INTERLEUKIN-4 (IL-4); TRANSFORMING GROWTH FACTOR BETA
   (TGF-BETA)
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC PROGENITOR CELLS;
   RECOMBINANT INTERFERON-ALPHA; TUMOR-NECROSIS-FACTOR; HIV-1-INFECTED
   SUBJECTS; MONOCYTES MACROPHAGES; INVITRO GROWTH; REPLICATION;
   PROLIFERATION; INTERLEUKIN-4
AB This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells, Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1(ADA), a monocytotropic strain of HIV-1, A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1(ADA) demonstrated that there was a productive infection, Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from noninfected CD34(+) cells, In contrast, when noninfected CD34(+) cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (CFU-GM) were detected in HN-infected LTC than in noninfected LTC, One week after the addition of CD34(+) cells, the number of CFU-GM in HIV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC, In those six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the number in noninfected LTC, The number of BFU-E in HIV-1-infected LTC was only 46 +/- 5% of the number in noninfected LTC (n = 5), There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM, Neutralizing antibody to tumor necrosis factor alpha (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC, The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferona-alpha. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-CM was approximately 2-fold greater after incubation of HIV-infected LTC with anti-interleukin-4 (IL-4), The effect of anti-TNF-alpha was variable, and anti-transforming growth factor-beta had no effect on the number of CFU GM in HIV-infected LTC, After 2 weeks, the number of CFU-GM in HN-infected LTC incubated with anti-IL-4 and anti-TNF-alpha was 2- to 4-fold greater than in untreated HIV-infected LTC, Antibody treatment did not promote an increase in the number of CFU CM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection. These results demonstrate that some cells in the stromal cell layers of LTC were targets for HIV-1(ADA), and that HIV-infected stromal cell layers suppressed or delayed the production of both CFU-GM and BFU-E. These results also suggest that hematopoietic suppression in HIV-infected LTC may be mediated by growth-in-hibitory cytokines that are different for erythropoiesis and myelopoiesis.
C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD.
   WALTER REED ARMY MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20307.
   WALTER REED ARMY MED CTR,DEPT CELLULAR IMMUNOL,WASHINGTON,DC 20307.
RP SCHWARTZ, GN (reprint author), NCI,MED BRANCH,TRANPLANTAT THERAPY SECT,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA.
NR 53
TC 15
Z9 15
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD JUN
PY 1995
VL 57
IS 6
BP 948
EP 955
PG 8
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA RE360
UT WOS:A1995RE36000021
PM 7540643
ER

PT J
AU BLANCHETTEMACKIE, EJ
   DWYER, NK
   BARBER, T
   COXEY, RA
   TAKEDA, T
   RONDINONE, CM
   THEODORAKIS, JL
   GREENBERG, AS
   LONDOS, C
AF BLANCHETTEMACKIE, EJ
   DWYER, NK
   BARBER, T
   COXEY, RA
   TAKEDA, T
   RONDINONE, CM
   THEODORAKIS, JL
   GREENBERG, AS
   LONDOS, C
TI PERILIPIN IS LOCATED ON THE SURFACE-LAYER OF INTRACELLULAR LIPID
   DROPLETS IN ADIPOCYTES
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE TRIACYLGLYCEROL; ENDOPLASMIC RETICULUM; LIPID DROPLET SURFACE LAYER;
   PEROXISOMES; MAMMARY GLAND; FREEZE-FRACTURE; CONFOCAL MICROSCOPY
ID RAT-LIVER PEROXISOMES; ENDOPLASMIC-RETICULUM; ADIPOSE CONVERSION;
   GENE-EXPRESSION; BIOSYNTHESIS; BIOGENESIS; GLOBULES; CELLS;
   LOCALIZATION; LIPOPROTEIN
AB Immunocytochemistry was used to determine the intracellular location of perilipins in adipocytes and the occurrence of these proteins in tissues involved in triacylglycerol metabolism. Confocal microscopy and 3-dimensional analysis of 3T3-L1 adipocytes showed that perilipin immunofluorescence, present on the surfaces of all sized lipid droplets, appeared unevenly dispersed on the surfaces of many large lipid droplets. Electron microscopy revealed that immunogold staining for perilipin was located directly on the surface layer apposed to and surrounding the core triacylglycerol of intracellular lipid droplets of adipocytes in culture or from white and brown adipose tissue. Freeze-fracture electron microscopy indicated that the hydrophobic face of this surface monolayer contained particles identical in size and distribution to intramembranous particles (IMPs), which are unique structural features of the hydrophobic faces of bilayered membranes. Also, freeze-fracture replicas revealed areas of continuity between the surface layer of lipid droplets and the membrane leaflets of endoplasmic reticulum, suggesting that the droplet monolayer surface is an area of endoplasmic reticulum membrane leaflet modified by its unique content of perilipin. Microperoxisomes, identified by immunostaining for catalase, were found closely associated with lipid droplets, but external to and not in contact with the lipid droplet surface layer. Vimentin, identified by immunofluorescence, was present around the periphery of most lipid droplets in 3T3-L1 cells during early stages of adipocyte development but, in contrast to perilipins, vimentin was not around the periphery of many large lipid droplets in mature cells. Although perilipin was at the surface of lipid droplets in adipocytes of lactating mammary gland, none was found to be associated with the milk lipid droplets in alveolar epithelial cells, nor was the protein found on the surfaces of lipid droplets in hepatocytes. Studies in mammary gland show that perilipin immunostaining will be a valuable tool for the identification of tissue adipocytes severely depleted of their triacylglycerol stores and thus without their characteristic spherical shape. Perilipin's singular location on the surface monolayer of intracellular lipid droplets supports an intimate role for the protein in the triacylglycerol metabolic functions of adipocytes.
C1 NIDDKD,CELLULAR & DEV BIOL LAB,MEMBRANE REGULAT SECT,BETHESDA,MD 20892.
RP BLANCHETTEMACKIE, EJ (reprint author), NIDDKD,CELL BIOCHEM & BIOL LAB,LIPID CELL BIOL SECT,BETHESDA,MD 20892, USA.
NR 45
TC 298
Z9 304
U1 2
U2 18
PU LIPID RESEARCH INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD JUN
PY 1995
VL 36
IS 6
BP 1211
EP 1226
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RG151
UT WOS:A1995RG15100006
PM 7665999
ER

PT J
AU ALTIERI, AS
   BYRD, RA
AF ALTIERI, AS
   BYRD, RA
TI RANDOMIZATION APPROACH TO WATER SUPPRESSION IN MULTIDIMENSIONAL NMR
   USING PULSED-FIELD GRADIENTS
SO JOURNAL OF MAGNETIC RESONANCE SERIES B
LA English
DT Note
ID SOLVENT-SATURATION-TRANSFER; TAILORED EXCITATION; AQUEOUS-SOLUTIONS;
   H-1-NMR SPECTRA; PROTON NMR; SPECTROSCOPY; PROTEINS; RESOLUTION; INVIVO;
   PHASE
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702.
RI Byrd, R. Andrew/F-8042-2015
OI Byrd, R. Andrew/0000-0003-3625-4232
FU NCI NIH HHS [N01-CO-74101]
NR 29
TC 28
Z9 28
U1 0
U2 6
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 1064-1866
J9 J MAGN RESON SER B
JI J. Magn. Reson. Ser. B
PD JUN
PY 1995
VL 107
IS 3
BP 260
EP 266
DI 10.1006/jmrb.1995.1086
PG 7
WC Physics, Atomic, Molecular & Chemical
SC Physics
GA RD118
UT WOS:A1995RD11800007
PM 7788099
ER

PT J
AU KUSZEWSKI, J
   GRONENBORN, AM
   CLORE, GM
AF KUSZEWSKI, J
   GRONENBORN, AM
   CLORE, GM
TI THE IMPACT OF DIRECT REFINEMENT AGAINST PROTON CHEMICAL-SHIFTS ON
   PROTEIN-STRUCTURE DETERMINATION BY NMR
SO JOURNAL OF MAGNETIC RESONANCE SERIES B
LA English
DT Note
ID SECONDARY STRUCTURE; DYNAMICS
RP KUSZEWSKI, J (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA.
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
NR 26
TC 108
Z9 108
U1 0
U2 7
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 1064-1866
J9 J MAGN RESON SER B
JI J. Magn. Reson. Ser. B
PD JUN
PY 1995
VL 107
IS 3
BP 293
EP 297
DI 10.1006/jmrb.1995.1093
PG 5
WC Physics, Atomic, Molecular & Chemical
SC Physics
GA RD118
UT WOS:A1995RD11800014
PM 7788102
ER

PT J
AU MCNELLIS, D
AF MCNELLIS, D
TI A VIEW FROM BETHESDA - NIH-CONSENSUS-DEVELOPMENT-CONFERENCE ON THE
   EFFECT OF CORTICOSTEROIDS FOR FETAL MATURATION ON PERINATAL OUTCOMES
SO JOURNAL OF MATERNAL-FETAL INVESTIGATION
LA English
DT Editorial Material
RP MCNELLIS, D (reprint author), NICHHD,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0939-6322
J9 J MATERN-FETAL INVES
JI J. Matern.-Fetal Invest.
PD SUM
PY 1995
VL 5
IS 3
BP 122
EP 123
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA RR614
UT WOS:A1995RR61400002
ER

PT J
AU PHILLIPS, CD
   HUBBARD, RL
   DUNTEMAN, G
   FOUNTAIN, DL
   CZECHOWICZ, D
   COOPER, JR
AF PHILLIPS, CD
   HUBBARD, RL
   DUNTEMAN, G
   FOUNTAIN, DL
   CZECHOWICZ, D
   COOPER, JR
TI MEASURING PROGRAM PERFORMANCE IN METHADONE TREATMENT USING IN-TREATMENT
   OUTCOMES - AN ILLUSTRATION
SO JOURNAL OF MENTAL HEALTH ADMINISTRATION
LA English
DT Article
ID QUALITY
AB Quality measurement and quality assurance in substance abuse treatment have, over the past few years, become a major policy issue.  In addition, there is interest in the degree to which client outcomes can play a role in measuring treatment program performance.  This article discusses the movement toward outcome-based performance measurement in substance abuse treatment.  Examples of the products that such a performance measurement system might produce are provided.  Why outcomes must be case-mix adjusted is discussed.  In addition, using data from 18 methadone programs and more than 2,000 methadone clients from the Treatment Outcome Prospective Study, an illustration of case-mix-adjusted performance measurement is provided.
C1 VHI,FAIRFAX,VA.
   NIDA,DIV CLIN & SERV RES,LEXINGTON,KY 40583.
RP PHILLIPS, CD (reprint author), RES TRIANGLE INST,SUBSTANCE ABUSE TREATMENT RES PROGRAM,POB 12194,RES TRIANGLE PK,NC 27709, USA.
FU PHS HHS [271-89-8532]
NR 15
TC 7
Z9 7
U1 0
U2 1
PU SAGE PUBL INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320
SN 0092-8623
J9 J MENT HEALTH ADMIN
JI J. Ment. Health Adm.
PD SUM
PY 1995
VL 22
IS 3
BP 214
EP 225
DI 10.1007/BF02521117
PG 12
WC Health Policy & Services
SC Health Care Sciences & Services
GA RL617
UT WOS:A1995RL61700002
PM 10172390
ER

PT J
AU MATHIOPOULOS, KD
   LANZARO, GC
AF MATHIOPOULOS, KD
   LANZARO, GC
TI DISTRIBUTION OF GENETIC DIVERSITY IN RELATION TO CHROMOSOMAL INVERSIONS
   IN THE MALARIA MOSQUITO ANOPHELES-GAMBIAE
SO JOURNAL OF MOLECULAR EVOLUTION
LA English
DT Article
DE NUCLEOTIDE DIVERSITY; INVERSION EVOLUTION; LINKED GENE COMPLEX;
   HITCHHIKING; SELECTIVE SWEEP
ID DROSOPHILA; COMPLEX; DNA
AB The epidemiology of malaria in Africa is complicated by the fact that its principal vector, the mosquito Anopheles gambiae, constitutes a complex of six sibling species. Each species is characterized by a unique array of paracentric inversions, as deduced by karyotypic analysis. In addition, most of the species carry a number of polymorphic inversions. In order to develop an understanding of the evolutionary histories of different parts of the genome, we compared the genetic variation of areas inside and outside inversions in two distinct inversion karyotypes of A. gambiae. Thirty-five cDNA clones were mapped on the five arms of the A. gambiae chromosomes with divisional probes. Sixteen of these clones, localized both inside and outside inversions of chromosome 2, were used as probes in order to determine the nucleotide diversity of different parts of the genome in the two inversion karyotypes. We observed that the sequence diversity inside the inversion is more than threefold lower than in areas outside the inversion and that the degree of divergence increases gradually at loci at increasing distance from the inversion. To interpret the data we present a selectionist and a stochastic model, both of which point to a relatively recent origin of the studied inversion and may suggest differences between the evolutionary history of inversions in Anopheles and Drosophila species.
C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892.
OI Mathiopoulos, Kostas/0000-0002-2875-5697
NR 22
TC 13
Z9 13
U1 1
U2 3
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0022-2844
J9 J MOL EVOL
JI J. Mol. Evol.
PD JUN
PY 1995
VL 40
IS 6
BP 578
EP 584
DI 10.1007/BF00160504
PG 7
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
GA QZ905
UT WOS:A1995QZ90500005
PM 7643407
ER

PT J
AU HOEHE, MR
   OTTERUD, B
   HSIEH, WT
   MARTINEZ, MM
   STAUFFER, D
   HOLIK, J
   BERRETTINI, WH
   BYERLEY, WF
   GERSHON, ES
   LALOUEL, JM
   LEPPERT, M
AF HOEHE, MR
   OTTERUD, B
   HSIEH, WT
   MARTINEZ, MM
   STAUFFER, D
   HOLIK, J
   BERRETTINI, WH
   BYERLEY, WF
   GERSHON, ES
   LALOUEL, JM
   LEPPERT, M
TI GENETIC-MAPPING OF ADRENERGIC-RECEPTOR GENES IN HUMANS
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE ADRENERGIC RECEPTORS; HUMAN GENETICS; RESTRICTION FRAGMENT LENGTH
   POLYMORPHISM; CHROMOSOME MAPPING; LINKAGE; GENETICS
ID HUMAN BETA-2-ADRENERGIC RECEPTOR; ALPHA-2-ADRENERGIC RECEPTOR; GENOMIC
   ORGANIZATION; INVERSE REGULATION; MOLECULAR-CLONING; DNA POLYMORPHISM;
   HUMAN-BRAIN; RAT-BRAIN; EXPRESSION; CDNA
AB We have genetically mapped the genes encoding four human adrenergic receptors (ARs) of subtypes alpha(1)C, alpha(2)A, alpha(2) beta, and beta(1), which are prototypic G protein coupled receptors that mediate the physiological effects of neurotransmitters, hormones, and drugs. We placed these genes onto the Cooperative Human Linkage Center (CHLC) and Genethon framework maps, within confidence intervals with greater than 1000:1 odds. With multipoint analysis the alpha(1)C gene (locus ADRA1C) mapped to the interval between NEFL and D8S283; alpha(2)C4, the gene encoding the alpha(2)C AR (locus ADRA2C), mapped to the interval between D4S126 and D4S62; and the alpha(2)-C10 (alpha(2)A AR)/beta(1) haplotype (loci ADRA2A/ADRB1) mapped to the interval between D10S259 and D10S187. A fifth AR gene, beta(2), yielded significant LOD scores with markers on the long arm of chromosome 5; however, this locus (ADRB2) could not be mapped to any specific interval with odds of greater than 1000:1. The two AR genes that are completely linked, alpha(2)-C10 and beta(1), were oriented on their shared 225-kb genomic fragment relative to the direction of transcription, with beta(1) being 5' to alpha(2)-C10. The positioning of these genes on high-density framework maps allows them to be tested as candidates in a spectrum of diseases that might involve AR dysfunction.
C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892.
   UNIV UTAH,SCH MED,DEPT GENET,SALT LAKE CITY,UT 84112.
   INSERM,U155,F-75016 PARIS,FRANCE.
   UNIV UTAH,SCH MED,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112.
   UNIV UTAH,SCH MED,DEPT PSYCHIAT,SALT LAKE CITY,UT 84112.
   THOMAS JEFFERSON UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107.
RP HOEHE, MR (reprint author), MAX DELBRUCK CTR MOLEC MED,ROBERT ROSSLE STR 10,D-13122 BERLIN,GERMANY.
RI Martinez, Maria/B-3111-2013
OI Martinez, Maria/0000-0003-2180-4537
NR 59
TC 19
Z9 20
U1 0
U2 2
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0946-2716
J9 J MOL MED-JMM
JI J. Molec. Med.-JMM
PD JUN
PY 1995
VL 73
IS 6
BP 299
EP 306
PG 8
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA RF826
UT WOS:A1995RF82600004
PM 7583452
ER

PT J
AU MCKEE, TC
   CARDELLINA, JH
   DREYER, GB
   BOYD, MR
AF MCKEE, TC
   CARDELLINA, JH
   DREYER, GB
   BOYD, MR
TI THE PSEUDOCALANOLIDES - STRUCTURE REVISION OF CALANOLIDE-C AND
   CALANOLIDE-D
SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA
LA English
DT Note
ID MOSHER METHOD
AB Nmr spectra of synthetic structures corresponding to those initially reported for natural compounds calanolide C[1] and calanolide D[2] showed some subtle differences from those of the natural products. Further analysis has resulted in revision of the structures of the natural compounds, now renamed pseudocalanolides C[3] and D[4]. The absolute stereochemistry of pseudocalanolide C was established as [6S,7S,8R] using the modified Mosher's method.
C1 NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702.
NR 8
TC 15
Z9 16
U1 0
U2 0
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 JUN
PY 1995
VL 58
IS 6
BP 916
EP 920
DI 10.1021/np50120a015
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA RL762
UT WOS:A1995RL76200015
PM 7545738
ER

PT J
AU PETTIT, GR
   TAN, R
   ICHIHARA, Y
   WILLIAMS, MD
   DOUBEK, DL
   TACKETT, LP
   SCHMIDT, JM
   CERNY, RL
   BOYD, MR
   HOOPER, JNA
AF PETTIT, GR
   TAN, R
   ICHIHARA, Y
   WILLIAMS, MD
   DOUBEK, DL
   TACKETT, LP
   SCHMIDT, JM
   CERNY, RL
   BOYD, MR
   HOOPER, JNA
TI ANTINEOPLASTIC AGENTS .325. ISOLATION AND STRUCTURE OF THE HUMAN CANCER
   CELL-GROWTH INHIBITORY CYCLIC OCTAPEPTIDES PHAKELLISTATIN-10 AND
   PHAKELLISTATIN-11 FROM PHAKELLIA SP
SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA
LA English
DT Note
ID PEPTIDES; PHASE
AB The two new marine sponge (Phakellia sp., western Pacific Ocean) constituents, phakellistatin 10 [1] and 11 [2], were found to be cyclic octapeptides that significantly inhibited growth of the murine P-388 lymphocytic leukemia (ED(50) values of 2.1 and 0.20 mu g/ml, respectively) and human cancer cell lines. The structures were established based on results of extensive tandem ms/ms and high-field (500-MHz) 2D H-1- and C-13-nmr analyses. All of the amino acid units (except Trp, not determined) were found to correspond to the (S)-configuration.
C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287.
   UNIV NEBRASKA,MIDWEST CTR MASS SPECT,DEPT CHEM,LINCOLN,NE 68588.
   NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702.
RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA.
FU NCI NIH HHS [CA44344-01A1-06]
NR 18
TC 47
Z9 49
U1 0
U2 1
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 JUN
PY 1995
VL 58
IS 6
BP 961
EP 965
DI 10.1021/np50120a025
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA RL762
UT WOS:A1995RL76200025
PM 7673945
ER

PT J
AU TANIWAKI, T
   BECERRA, SP
   CHADER, GJ
   SCHWARTZ, JP
AF TANIWAKI, T
   BECERRA, SP
   CHADER, GJ
   SCHWARTZ, JP
TI PIGMENT EPITHELIUM-DERIVED FACTOR IS A SURVIVAL FACTOR FOR CEREBELLAR
   GRANULE CELLS IN CULTURE
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE NEUROTROPHINS; CEREBELLAR GRANULE CELLS; CNS DEVELOPMENT; SERPIN;
   NEURITE EXTENSION; MITOSIS
ID NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; NEUROTROPHIC FACTOR;
   INTERPHOTORECEPTOR MATRIX; TRANSMITTER SYSTEMS; NEURONS; GLUTAMATE;
   BRAIN; RAT; PROTEIN
AB Pigment epithelium-derived factor (PEDF), purified from human fetal retinal pigment epithelium cell culture medium, was shown to potentiate the differentiation of human Y-79 retinoblastoma cells. To investigate potential neurotrophic effects of PEDF on neurons other than those of retinal derivation, we used cultures of cerebellar granule cells. The number of cerebellar granule cells was significantly larger in the presence of PEDF, as demonstrated by an assay for viable cells that uses 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt, conversion, by cell count, and by immunocytochemistry. The effect of PEDF showed a dose-response relationship, with a larger effect in chemically defined medium than in serum-containing medium [ED(50) = 30 ng/ml (0.70 nM) in chemically defined medium and 100 ng/ml (2.3 nM) in serum-containing medium]. PEDF had no effect on incorporation of bromodeoxyuridine (cell proliferation) or on neurofilament content (neurite outgrowth) measured by an enzyme-linked immunoadsorbent assay. These results demonstrate that PEDF has a neurotrophic survival effect on cerebellar granule cells in culture and suggest the possibility that it may affect other CNS neurons as well.
C1 NEI, RETINAL CELL & MOLEC BIOL LAB, BETHESDA, MD 20892 USA.
RP TANIWAKI, T (reprint author), NINCDS, CLIN NEUROSCI BRANCH, BLDG 9, ROOM 1W115, BETHESDA, MD 20892 USA.
NR 49
TC 117
Z9 124
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 1995
VL 64
IS 6
BP 2509
EP 2517
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA QZ252
UT WOS:A1995QZ25200015
PM 7760030
ER

PT J
AU BASILE, AS
   SAITO, K
   LI, Y
   HEYES, MP
AF BASILE, AS
   SAITO, K
   LI, Y
   HEYES, MP
TI THE RELATIONSHIP BETWEEN PLASMA AND BRAIN QUINOLINIC ACID LEVELS AND THE
   SEVERITY OF HEPATIC-ENCEPHALOPATHY IN ANIMAL-MODELS OF FULMINANT
   HEPATIC-FAILURE
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE QUINOLINIC ACID; HEPATIC ENCEPHALOPATHY; RAT; RABBIT; BRAIN; PLASMA
ID BENZODIAZEPINE RECEPTOR LIGANDS; ACUTE LIVER-FAILURE; AMINO-ACID; RABBIT
   MODEL; CEREBROSPINAL-FLUID; L-TRYPTOPHAN; RAT-BRAIN; BLOOD;
   CHROMATOGRAPHY; PATHOGENESIS
AB Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three- to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations similar to 10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic L-tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized bloodbrain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor.
C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892.
RP BASILE, AS (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA.
NR 32
TC 15
Z9 16
U1 2
U2 3
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 1995
VL 64
IS 6
BP 2607
EP 2614
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA QZ252
UT WOS:A1995QZ25200027
PM 7760040
ER

PT J
AU KELLY, JF
   JOSEPH, JA
   DENISOVA, NA
   ERAT, S
   MASON, RP
   ROTH, GS
AF KELLY, JF
   JOSEPH, JA
   DENISOVA, NA
   ERAT, S
   MASON, RP
   ROTH, GS
TI DISSOCIATION OF STRIATAL GTPASE AND DOPAMINE RELEASE RESPONSES TO
   MUSCARINIC CHOLINERGIC AGONISTS IN F344 RATS - INFLUENCE OF AGE AND
   DIETARY MANIPULATION
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE DIET; MEMBRANE; AGING; LIPIDS; CHOLINERGIC RECEPTORS; DOMAINS
ID FATTY-ACID COMPOSITION; PHOSPHOLIPID TURNOVER; BRAIN MEMBRANES;
   CHOLESTEROL; RECEPTORS; METABOLISM; DOMAINS; INVIVO; MYELIN; STIMULATION
AB There is evidence that dietary lipids and age both influence neuronal membrane composition and receptor G protein-linked signal transduction, but very little information is available on the interaction between these two factors. To investigate this, we obtained striata from 2, 12, and 22-month-old male F344 rats who were fed either a high-cholesterol, high-saturated fat or low-fat diet for 1 month. The striata were assayed for muscarinic agonist-stimulated low-K-m GTPase activity using 10(-3) M carbachol and 10(-5) M oxotremorine and for KCI-evoked dopamine release enhancement by 10(-5) M oxotremorine. Membrane cholesterol and phospholipid content and phospholipid class composition were also determined. Mature animals showed significant but divergent changes in GTPase activity and dopamine release for high-cholesterol and low-fat diets: GTPase activity decreased, whereas dopamine release increased in these groups. Alterations in GTPase activity but not in dopamine release were inversely correlated with the cholesterol/phospholipid molar ratio. Old control animals showed reductions in both GTPase activity and oxotremorine-enhanced dopamine release compared with young animals. Whereas none of the experimental diets affected GTPase activity in old animals, the low-fat diet produced a marked decrease in dopamine release. In contrast to mature and old groups, young rats showed no significant change in either GTPase or dopamine release, suggesting a relative ''resistance'' to such dietary lipid modulation. The observed dissociation in GTPase and dopamine release responses to diet may reflect differing effects of these diets on discrete membrane lipid domains that preferentially influence different signal transduction components. The substantial age-related differences in striatal membrane response to dietary lipid modulation may represent the effects of underlying age differences in membrane lipid metabolism, structure, and/or dynamics, Our findings support the work of other groups that have shown that brain membranes are susceptible to modification by exogenous lipids. They also suggest the need for a more systematic examination of the influence of age on the response to other types of dietary lipid changes.
C1 TUFTS UNIV,USDA,AGING RES CTR,BOSTON,MA 02111.
   MED COLL PENN,NEUROSCI RES CTR,PITTSBURGH,PA.
RP KELLY, JF (reprint author), NIA,JOHNS HOPKINS BAYVIEW MED CTR,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224, USA.
NR 60
TC 24
Z9 24
U1 0
U2 0
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 1995
VL 64
IS 6
BP 2755
EP 2764
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA QZ252
UT WOS:A1995QZ25200045
PM 7760056
ER

PT J
AU GOLDSTEIN, DS
   HAHN, SH
   HOLMES, C
   TIFFT, C
   HARVEYWHITE, J
   MILSTIEN, S
   KAUFMAN, S
AF GOLDSTEIN, DS
   HAHN, SH
   HOLMES, C
   TIFFT, C
   HARVEYWHITE, J
   MILSTIEN, S
   KAUFMAN, S
TI MONOAMINERGIC EFFECTS OF FOLINIC ACID, L-DOPA, AND 5-HYDROXYTRYPTOPHAN
   IN DIHYDROPTERIDINE REDUCTASE DEFICIENCY
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Note
DE DIHYDROPTERIDINE REDUCTASE; TETRAHYDROBIOPTERIN; PHENYLKETONURIA;
   CATECHOLS; DOPA; NOREPINEPHRINE; DOPAMINE; SEROTONIN;
   DIHYDROXYPHENYLACETIC ACID; DIHYDROXYPHENYLGLYCOL; HOMOVANILLIC ACID;
   5-HYDROXYINDOLEACETIC ACID; 5-HYDROXYTRYPTOPHAN
ID HYPERPHENYLALANINEMIA; DIAGNOSIS; PTERINS; PLASMA; ENZYME; ASSAY
AB Plasma and CSF concentrations of endogenous L-DOPA, catecholamines, and metabolites of monoamines were assayed in a patient with atypical phenylketonuria due to absent dihydropteridine reductase (DHPR), before and during treatment with folinic acid, Sinemet, and 5-hydroxytryptophan The patient had low but detectable levels of L-DOPA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) in plasma and low but detectable levels of these compounds and of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF, with approximately normal plasma and CSF levels of norepinephrine [noradrenaline (NA)]. Folinic acid treatment approximately doubled plasma levels of L-DOPA, NA, DOPAC, and DHPG, compared with values during dietary phenylalanine restriction alone. Detection of L-DOPA, catecholamines, and monoamine metabolites in this patient indicates that monoamine synthesis in humans does not absolutely require DHPR. The results are consistent with the existence of an alternative biochemical pathway, with folinic acid treatment augmenting activity along this pathway. Low plasma levels of L-DOPA, DOPAC, and DHPG may reflect decreased catecholamine synthesis and turnover in sympathetic nerves, with compensatory increases in exocytotic release normalizing plasma NA levels. Key Words: Dihydropteridine reductase-Tetrahydrobiopterin-Phenylketonuria--Catechols- DOPA-Norepinephrine-Dopamine-Serotonin-Dihydroxyphenylacetic acid-Dihydroxyphenylglycol--Homovanillic acid-5-Hydroxyindoleacetic acid--5-Hydroxytryptophan.
C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892.
   NIMH,NEUROCHEM LAB,BETHESDA,MD 20892.
   CHILDRENS NATL MED CTR,WASHINGTON,DC 20010.
RP GOLDSTEIN, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,RM 6N252,BETHESDA,MD 20892, USA.
NR 11
TC 12
Z9 12
U1 0
U2 1
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 1995
VL 64
IS 6
BP 2810
EP 2813
PG 4
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA QZ252
UT WOS:A1995QZ25200051
PM 7760062
ER

PT J
AU MAIER, WE
   BROWN, HW
   TILSON, HA
   LUSTER, MI
   HARRY, GJ
AF MAIER, WE
   BROWN, HW
   TILSON, HA
   LUSTER, MI
   HARRY, GJ
TI TRIMETHYLTIN INCREASES INTERLEUKIN(IL)1-ALPHA, IL-6 AND
   TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA LEVELS IN RAT HIPPOCAMPUS
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE CYTOKINES; HIPPOCAMPUS; TRIMETHYLTIN; GLIAL FIBRILLARY ACIDIC PROTEIN
ID CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-1-BETA MESSENGER-RNA; FIBRILLARY
   ACIDIC PROTEIN; MULTIPLE-SCLEROSIS BRAIN; EXPRESSION; ASTROCYTES;
   INVOLVEMENT; INDUCTION; PROLIFERATION; IL-1-BETA
AB Within the central nervous system (CNS), cytokines are thought to have active roles in pathophysiological changes seen in various neurological diseases and trauma. The present study was undertaken to examine the early response of pro-inflammatory cytokines following exposure to a specific neurotoxicant (trimethyltin; TMT). mRNA levels for interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor (TNF) alpha were measured in the hippocampus of adult male Long-Evans hooded rats following an acute injection of trimethyltin hydroxide (8 mg TMT/kg body weight). At various times following exposure (6 h to 8 days), hippocampal tissues were excised and relative changes in cytokine mRNA levels were assessed by reverse transcription and polymerase chain reaction. lL-1 alpha, IL-6 and TNF alpha mRNA levels in the hippocampus increased within 6 h and remained elevated for 8 days. Quantitative analysis of mRNA transcripts revealed a two-fold increase in both IL-6 and TNF alpha within 6 h and a continued elevation of TNF alpha to 9-fold by 12 h. Within 96 h, glial fibrillary acidic protein (GFAP) mRNA levels were elevated in the hippocampus. Histological examination showed sparse individual neuronal necrosis at this time in both the pyramidal and granule cell regions with no increase in astrocyte GFAP immunoreactivity. However, an early, 24 h, response of microglial cells was indicated by increased lectin binding. This morphological profile progressed over time to a profound neuronal loss in the CA3-4 granule cell layer and marked astrocyte hypertrophy. The onset of pro-inflammatory cytokine mRNA expression appears to be temporally associated with histological evidence of elevated microglia in the hippocampus. It is proposed that microglia and pro-inflammatory cytokines play a modulatory role in the early stages of TMT-induced neurotoxicity.
C1 NIEHS, ENVIRONM IMMUNOL & NEUROBIOL SECT, RES TRIANGLE PK, NC 27709 USA.
   UNIV N CAROLINA, CURRICULUM TOXICOL, CHAPEL HILL, NC USA.
   US EPA, HLTH EFFECTS RES LAB, DIV NEUROTOXICOL, RES TRIANGLE PK, NC 27711 USA.
FU NIEHS NIH HHS [T32ES07126]
NR 44
TC 57
Z9 57
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
EI 1872-8421
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD JUN
PY 1995
VL 59
IS 1-2
BP 65
EP 75
DI 10.1016/0165-5728(95)00026-X
PG 11
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA RE736
UT WOS:A1995RE73600008
PM 7797621
ER

PT J
AU MUNOZ, DP
   WURTZ, RH
AF MUNOZ, DP
   WURTZ, RH
TI SACCADE-RELATED ACTIVITY IN MONKEY SUPERIOR COLLICULUS .1.
   CHARACTERISTICS OF BURST AND BUILDUP CELLS
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID ORIENTING GAZE SHIFTS; ALERT RHESUS-MONKEY; HEAD-FREE CAT;
   EYE-MOVEMENTS; TECTORETICULOSPINAL SYSTEM; EFFERENT NEURONS; BEHAVING
   MONKEY; SINGLE UNITS; PRIMATE; STIMULATION
AB 1. In the monkey superior colliculus (SC), the activity of most saccade-related neurons studied so far consists of a burst of activity in a population of cells at one place on the SC movement map. In contrast, recent experiments in the cat have described saccade-related activity as a slow increase in discharge before saccades followed by a hill of activity moving across the SC map. In order to explore this striking difference in the distribution of activity across the SC, we recorded from all saccade-related neurons that we encountered in microelectrode penetrations through the monkey SC and placed them in categories according to their activity during the generation of saccades.
   2. When we considered the activity preceding the onset of the saccade, we could divide the cells into two categories. Cells with burst activity had a high-frequency discharge just before saccade onset but little activity between the signal to make a saccade and saccade onset. About two thirds of the saccade-related cells had only a burst of activity. Cells with a buildup of activity began to discharge at a low frequency after the signal to make a saccade and the discharge continued until generation of the saccade. About one third of the saccade-related cells studied had a buildup of activity, and about three fourths of these cells also gave a burst of activity with the saccade in addition to the slow buildup of activity.
   3. The buildup of activity seemed to be more closely related to preparation to make a saccade than to the generation of the saccade. The buildup developed even in cases when no saccade occurred.
   4. The falling phase of the discharge of these saccade-related cells stopped with the end of the saccade (a clipped discharge), shortly after the end of the saccade (partially clipped), or long after the end of the saccade (unclipped).
   5. Some cells had closed movement fields in which saccades that were substantially smaller or larger than the optimal amplitude were not associated with increased activity. Other cells tended to have open-ended movement fields without any peripheral border; they were active for all saccades of optimal direction whose amplitudes were equal to or greater than a given amplitude. We found both types of movement fields at all movement field eccentricities studied within the SC.
   6. The activity of cells with open-ended movement fields did not result from the smear of the visual target as it swept across the retina during a saccade because the discharge of the cell was still present when saccades were made in the dark to remembered rather than visual targets. The activity of these cells was also not due to the occurrence of corrective saccades because the activity was visible whether or not there was one.
   7. In penetrations through the intermediate layers of the SC, we usually found cells with a burst of activity and those with closed movement fields to Lie more dorsally than those with a buildup of activity and open-ended movement fields.
   8. We also compared the activity of the saccade-related cells with the activity of fixation cells located in the rostral pole of the SC. We found transition between saccade-related cells with open-ended movement fields and fixation cells. Cells within this transition zone were tonically active during fixation but also discharged during small contraversive saccades. These fixation cells were encountered deeper in the intermediate layers, at the same level as the cells with open-ended movement fields and buildup of activity. We propose that fixation cells form a rostral extension of the layer of cells with a buildup of activity.
   9. We conclude that these characteristics of the saccade-related cells overlap sufficiently to allow us to place the cells into two groups. Burst cells have a high-frequency burst occurring immediately before saccades and no buildup of activity; the majority have clipped activity at the end of the saccade and usually have closed movement fields. In contrast, buildup cells show activity beginning with the signal to make a saccade that continues until the generation of the saccade; the majority have partially clipped activity at the end of the saccade and have open-ended movement fields. Because we encountered the cells with burst activity and closed movement fields more dorsally than we did cells with buildup activity and open-ended movement fields, we hypothesize further that the burst and buildup cells can be regarded as separate functional sublayers with the burst layer on top and the buildup layer below. The buildup cells are similar to the saccade-related cells in the cat SC, but the burst cells may be an added feature of the primate SC.
C1 QUEENS UNIV,DEPT PHYSIOL,MRC,SENSORY MOTOR PHYSIOL GRP,KINGSTON,ON K7L 3N6,CANADA.
RP MUNOZ, DP (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA.
NR 52
TC 405
Z9 406
U1 3
U2 14
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUN
PY 1995
VL 73
IS 6
BP 2313
EP 2333
PG 21
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA RD793
UT WOS:A1995RD79300016
PM 7666141
ER

PT J
AU MUNOZ, DP
   WURTZ, RH
AF MUNOZ, DP
   WURTZ, RH
TI SACCADE-RELATED ACTIVITY IN MONKEY SUPERIOR COLLICULUS .2. SPREAD OF
   ACTIVITY DURING SACCADES
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID ORIENTING GAZE SHIFTS; HEAD-FREE CAT; PARIETAL ASSOCIATION CORTEX;
   INHIBITORY BURST NEURONS; SUPPLEMENTARY EYE FIELD; ALERT
   SQUIRREL-MONKEY; NEURAL NETWORK MODEL; TECTORETICULOSPINAL SYSTEM;
   FUNCTIONAL-PROPERTIES; EXPRESS SACCADES
AB 1. In the companion paper we described two classes of cells in the monkey superior colliculus (SC) that were related to saccade generation, buildup cells and burst cells, which fell into two functional sublayers within the intermediate layers of the SC. Fixation cells in the rostral SC were deemed to be part of the buildup cell layer. The buildup cells had several characteristics in common with cells in the cat described as having a ''hill of activity'' moving across the SC, but the burst cells had no such characteristics. In this paper we further investigate whether there is evidence for such a moving hill of activity in the monkey by analyzing the spatial and temporal activity of cells across the SC during the generation of visually guided saccades.
   2. We recorded the activity of single cells while the monkey made saccades of different amplitudes (0.5-60 degrees). We recorded cells from locations extending from the rostral to caudal SC in order to sample cells whose optimal amplitudes ranged from small to large saccades. This allowed us to see any shift of activity across the SC before, during, and after saccades. It also allowed us to determine the fraction of the SC that was active during the successive phases of saccade generation.
   3. During active visual fixation, the fixation cells in the rostral pole of the buildup layer showed an increased discharge rate. From the population reconstruction, we estimate that the zone of active cells spanned the most rostral 0.72 mm in each SC. Assuming the SC is 5 mm in length, similar to 15% of the cells lying along the horizontal meridian in the buildup layer would be active during fixation.
   4. At least 100 ms before the initiation of a saccade, long-lead activity began to appear in the buildup layer at the site on the SC motor map related to the next saccade. Fixation activity in the rostral poles simultaneously began to diminish, but the cells in the burst layer remained relatively silent.
   5. Approximately 25 ms before saccade onset, the fixation cells ceased firing and both burst and buildup cells began to burst. The active zone in the burst layer was estimated to be similar to 1.4 mm diam, occupying roughly 28% of the SC along a line sunning from the rostral pole through the center of the initially active zone. The size of this active area among the burst cells was independent of saccade amplitude. The size of the initially active zone in the buildup layer was larger than in the burst layer and was dependent on saccade amplitude; it was larger for larger saccades.
   6. During the saccade, all cells in the buildup layer lying rostral to the initially active zone became active, and their peak discharge occurred later in the saccade as the cells were located more rostrally. Cells lying caudal to the initially active buildup cells were not activated. During the saccade, activity in the burst cell layer collapsed, but there was no shift in the locus of this activity in the SC.
   7. We interpret the sequential activation of the buildup cells during a saccade as a spread of activity rostrally across the buildup layer of the SC. We saw no evidence for a spread of activity in the burst layer.
   8. These experiments allow us to propose the following sequence of activity among the SC cells during generation of a saccade. During fixation, activity is confined to the fixation cells in the rostral SC, and we hypothesize that these cells suppress saccades via inhibitory connections directly onto the saccade cells in the caudal SC and excitatory connections onto the omnipause neurons in the pens. The buildup cells show the earliest activity preceding a saccade, and we suggest that this activity is related to preparation to make a saccade, including selection of target amplitude and direction. The burst cells are active just before saccade onset and could provide input to the pens for the amplitude and direction of the saccade. The pause in activity of the fixation cells is critical for the timing of the saccade. We think that the rostral spread of activity in the buildup cells, and the sharp reduction in burst cell discharge, are consistent with a feedback signal to the SC from the pens. We conclude that these changes in the spatiotemporal distribution of activity in the monkey SC are critical for controlling when a saccade occurs, its amplitude and direction, and its trajectory.
C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892.
   QUEENS UNIV,DEPT PHYSIOL,MRC,SENSORY MOTOR PHYSIOL GRP,KINGSTON,ON K7L 3N6,CANADA.
NR 55
TC 207
Z9 209
U1 3
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUN
PY 1995
VL 73
IS 6
BP 2334
EP 2348
PG 15
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA RD793
UT WOS:A1995RD79300017
PM 7666142
ER

PT J
AU VANNELLI, GB
   ENSOLI, F
   ZONEFRATI, R
   KUBOTA, YH
   ARCANGELI, A
   BECCHETTI, A
   CAMICI, G
   BARNI, T
   THIELE, CJ
   BALBONI, GC
AF VANNELLI, GB
   ENSOLI, F
   ZONEFRATI, R
   KUBOTA, YH
   ARCANGELI, A
   BECCHETTI, A
   CAMICI, G
   BARNI, T
   THIELE, CJ
   BALBONI, GC
TI NEUROBLAST LONG-TERM CELL-CULTURES FROM HUMAN FETAL OLFACTORY EPITHELIUM
   RESPOND TO ODORS
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE PRIMARY CULTURES; NEUROBLASTS; STEM CELLS; OLFACTORY NEUROGENESIS;
   ODORANTS; CAMP
ID NEUROFILAMENT TRIPLET PROTEINS; SENSITIVE ADENYLATE-CYCLASE;
   NEURON-SPECIFIC ENOLASE; INTERMEDIATE FILAMENTS; ADHESION MOLECULES;
   MARKER PROTEIN; RECEPTOR NEURONS; SENSORY NEURONS; NERVOUS-SYSTEM; GATED
   CHANNEL
AB Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine, In addition, patch-clamp experiments reveal that these cells are electrically excitable, Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro, The results suggest that these cells originate from the ''stem cell'' compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation.
C1 UNIV FLORENCE,MED CLIN 3,I-50134 FLORENCE,ITALY.
   UNIV FLORENCE,INST GEN PATHOL,I-50134 FLORENCE,ITALY.
   UNIV FLORENCE,INST BIOCHEM,I-50134 FLORENCE,ITALY.
   UNIV MILAN,DEPT GEN PHYSIOL & BIOCHEM,MILAN,ITALY.
   UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720.
   NCI,CELLULAR & MOLEC BIOL SECT,BETHESDA,MD.
RP VANNELLI, GB (reprint author), UNIV FLORENCE,DEPT HUMAN ANAT & HISTOL,VIALE MORGAGNI 85,I-50134 FLORENCE,ITALY.
OI BARNI, Tullio/0000-0002-9044-4929
NR 78
TC 46
Z9 46
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN
PY 1995
VL 15
IS 6
BP 4382
EP 4394
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA RD299
UT WOS:A1995RD29900021
PM 7790915
ER

PT J
AU LIEBERMAN, DM
   LASKE, DW
   MORRISON, PF
   BANKIEWICZ, KS
   OLDFIELD, EH
AF LIEBERMAN, DM
   LASKE, DW
   MORRISON, PF
   BANKIEWICZ, KS
   OLDFIELD, EH
TI CONVECTION-ENHANCED DISTRIBUTION OF LARGE MOLECULES IN GRAY-MATTER
   DURING INTERSTITIAL DRUG INFUSION
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE INTERSTITIAL INFUSION; DRUG DELIVERY; BULK FLOW; AUTORADIOGRAPHY; RAT;
   RHESUS MONKEY
ID BLOOD-BRAIN-BARRIER; RAT-BRAIN; TISSUE; PERFUSION; FLUID;
   MACROMOLECULES; MICROINFUSION; CHEMOTHERAPY; ANTEROGRADE; DIFFUSION
AB Many novel experimental therapeutic agents, such as neurotrophic factors, enzymes, biological modifiers, and genetic vectors, do not readily cross the blood-brain barrier. An effective strategy to deliver these compounds to the central nervous system is required for their application in vivo. Under normal physiological conditions, brain interstitial fluid moves by both bulk flow (convection) and diffusion. It has recently been shown that interstitial infusion into the white matter can be used to increase bulk flow, produce interstitial convection, and efficiently and homogeneously deliver drugs to large regions of brain without significant functional or structural damage. In theory, even more uniform distribution is likely in gray matter.
   In the current study, four experiments were performed to examine if convection-enhanced delivery could be used to achieve regional distribution of large molecules in gray matter. First, the volume and consistency of anatomical distribution of 20 mu l of phaseolus valgaris-leukoagglutinin (PHA-L; molecular weight (MW) 126 kD) after continuous high-flow microinfusion into the striatum of five rats over 200 minutes were determined using immunocytochemistry and quantified with image analysis. Second, the concentration profile of C-14 albumin (MW 69 kD) infused under identical conditions was determined in four hemispheres using quantitative autoradiography. Third, the volume of distribution after convection-enhanced infusion of 250 or 500 mu l biotinylated dextran (b-dextran, MW 10 kD), delivered over 310 minutes into the caudate and putamen of a rhesus monkey from one (250 mu I) or two (500 mu l) cannulas, was determined using immunocytochemistry and quantified with image analysis. Finally, the ability to target all dopaminergic neurons of the nigrostriatal tract via perfusion of the striatum with subsequent retrograde transport was assessed in three experiments by immunohistochemical analysis of the mesencephalon following a 300-minute infusion of 27 mu l horseradish peroxidase-labeled wheat germ agglutinin (WGA-HRP) into the striatum.
   Convection-enhanced delivery reproducibly distributed the large-compound PHA-L throughout the rat striatum (the percent volume of the striatum perfused, V-s, was 86% +/- 5%; mean +/- standard deviation) and produced a homogeneous tissue concentration in the perfused region (concentration of C-14-albumin relative to infusate concentration 30% +/- 5%). In the monkey, the infusion widely distributed b-dextran within the striatum using one cannula (caudate and putamen V-s = 76% and 76%) or two cannulas (V-s = 90% and 71%). Perfusion of the rat striatum with WGA-HRP effectively targeted neurons throughout the pars compacta of the substantia nigra via their efferent connections in the nigrostriatal pathway.
   Convection-enhanced infusion into gray matter distributes large molecules extensively at a relatively homogeneous concentration. This technique for effective acute delivery of large molecules into the gray matter has several advantages over diffusion alone and has a wide spectrum of potential applications in laboratory and clinical neuroscience.
C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892.
   NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892.
RI Kipke, Daryl/A-2167-2009
NR 31
TC 247
Z9 252
U1 2
U2 11
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 JUN
PY 1995
VL 82
IS 6
BP 1021
EP 1029
DI 10.3171/jns.1995.82.6.1021
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA QZ904
UT WOS:A1995QZ90400017
PM 7539062
ER

PT J
AU LEHKY, TJ
   JACOBSON, S
AF LEHKY, TJ
   JACOBSON, S
TI INDUCTION OF HLA CLASS-II IN HTLV-I INFECTED NEURONAL CELL-LINES
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE HTLV-I; HUMAN NEURONAL CELL LINES; HLA CLASS II
ID TROPICAL SPASTIC PARAPARESIS; VIRUS TYPE-I; CENTRAL-NERVOUS-SYSTEM;
   PERIPHERAL-BLOOD LYMPHOCYTES; MHC CLASS-II; SPINAL-CORD; NEUROLOGICAL
   DISEASE; ANTIGEN EXPRESSION; TRANS-ACTIVATION; ASTROGLIAL CELLS
AB Human T-lymphotropic virus-I (HTLV-I) has been etiologically linked with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurologic disease. The characteristic pathological finding in HAM/TSP is marked mononuclear infiltration of the CNS with destruction of the long tracts of the spinal cord. An increased expression of HLA surface antigens and cytokines in the CNS is associated with this inflammatory response. Furthermore, there is evidence for the presence of HTLV-I in HAM/TSP CNS specimens using in situ hybridization and polymerase chain reaction techniques. The relationship between HTLV-I infection of CNS cells and the observed upregulation of surface antigens in the CNS is not well understood. It has been previously demonstrated that HTLV-I infection of neuroblastoma cells leads to induction of HLA surface antigens. As an extension of these studies, HFGC and HCN-1a, neuronal cell lines of nontumorigenic origin, were infected with HTLV-I and the effect on HLA upregulation was studied. Infection of the neuronal cells was demonstrated by the presence of HTLV-I gp46 surface antigen on CD4 negative cells and by the in situ presence of HTLV-I RNA in neurofilament positive cells. Concurrent to HTLV-I infection, HLA class II surface antigen was observed on neurofilament positive cells. Upregulation of HLA class II was not observed in neuronal cells grown in the presence of interferon-gamma or tissue necrosis factor-alpha.
RP LEHKY, TJ (reprint author), NIH,NEUROIMMUNOL BRANCH,BLDG 10-RM 5B16,BETHESDA,MD 20892, USA.
NR 52
TC 3
Z9 3
U1 0
U2 0
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 1995
VL 1
IS 2
BP 145
EP 156
DI 10.3109/13550289509113961
PG 12
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA TG502
UT WOS:A1995TG50200003
PM 9222353
ER

PT J
AU ECKELMAN, WC
AF ECKELMAN, WC
TI DESIGNING A MOLECULAR PROBE FOR MUSCARINIC ACETYLCHOLINE-RECEPTOR
   (MACHR) IMAGING
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article; Proceedings Paper
CT Workshop on Molecular Nuclear Medicine
CY JAN 23-24, 1992
CL WASHINGTON, DC
SP US DOE, Med Applicat & Biophys Res Div, Off Hlth & Environm Res
ID RAT-BRAIN; BINDING; INVIVO
AB Radiolabeled molecular probes have demonstrated the potential for in vivo quantification of cell surface receptor concentration as a function of disease. Molecular biology has been instrumental in the design of these probes for in vivo studies, as exemplified by a molecular probe for muscarinic acetylcholine (mACh) receptor imaging. On a technical level, molecular biology has led to a better understanding of the selectivity of a radiolabeled probe in vitro, On a physiologic level, a combination of molecular biology and nuclear medicine provides an opportunity to validate in vivo what has been learned about receptors in vitro.
RP ECKELMAN, WC (reprint author), NCI,CTR CLIN,DEPT PET,BLDG 10,RM 1C450,BETHESDA,MD 20892, USA.
NR 19
TC 4
Z9 4
U1 0
U2 0
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD JUN
PY 1995
VL 36
IS 6
SU S
BP S5
EP S7
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA RD907
UT WOS:A1995RD90700003
PM 7769465
ER

PT J
AU LANE, MA
   REZNICK, AZ
   TILMONT, EM
   LANIR, A
   BALL, SS
   READ, V
   INGRAM, DK
   CUTLER, RG
   ROTH, GS
AF LANE, MA
   REZNICK, AZ
   TILMONT, EM
   LANIR, A
   BALL, SS
   READ, V
   INGRAM, DK
   CUTLER, RG
   ROTH, GS
TI AGING AND FOOD RESTRICTION ALTER SOME INDEXES OF BONE METABOLISM IN MALE
   RHESUS-MONKEYS (MACACA-MULATTA)
SO JOURNAL OF NUTRITION
LA English
DT Article
DE DIETARY RESTRICTION; BONE METABOLISM; MACACA MULATTA; AGING; DUAL ENERGY
   X-RAY ABSORPTIOMETRY
ID DIETARY RESTRICTION; ALKALINE-PHOSPHATASE; AGE; RATS; INTERLEUKIN-6;
   DENSITY; SEX; HYPERPARATHYROIDISM; TESTOSTERONE; MODULATION
AB Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long-term (>6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise
C1 TECHNION ISRAEL INST TECHNOL,FAC MED,DEPT MORPHOL SCI,IL-31086 HAIFA,ISRAEL.
   UNIV MISSISSIPPI,SCH MED,DEPT PATHOL,JACKSON,MS 39216.
RP LANE, MA (reprint author), NIA,HOPKINS BAYVIEW MED CTR,GERONTOL RES CTR,NATHAN SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224, USA.
NR 33
TC 52
Z9 52
U1 0
U2 1
PU AMER INST NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD JUN
PY 1995
VL 125
IS 6
BP 1600
EP 1610
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA RC958
UT WOS:A1995RC95800024
PM 7782913
ER

PT J
AU CHAN, CC
   MARTIN, DF
   XU, DS
   ROBERGE, FG
AF CHAN, CC
   MARTIN, DF
   XU, DS
   ROBERGE, FG
TI SIDE-EFFECTS OF RAPAMYCIN IN THE RAT
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
AB The side effects of Rapamycin was evaluated by histopathological examination of the heart, kidneys, and eyes of treated Lewis rats. Rapamycin was administered during 14 days by continuous intravenous infusions at doses of 0.5, 1.0, and 1.5 mg/kg/day. Focal myocardial infarction was observed in three of five rats with Rapamycin given at 1.5 mg/kg/day and two of 22 rats with 1.0 mg/kg/day. There were no sign of myocardial toxicity at a Rapamycin dose of 0.5 mg/kg/day. The retina of one eye of a rat treated at a dose of 1.5 mg/kg/day had a small area of focal ischemic necrosis. The kidneys were normal at all doses.
RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 0
TC 10
Z9 10
U1 0
U2 2
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538
SN 1080-7683
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD SUM
PY 1995
VL 11
IS 2
BP 177
EP 181
DI 10.1089/jop.1995.11.177
PG 5
WC Ophthalmology; Pharmacology & Pharmacy
SC Ophthalmology; Pharmacology & Pharmacy
GA RJ957
UT WOS:A1995RJ95700009
PM 8564638
ER

PT J
AU HUSSON, RN
   LAN, Y
   KOJIMA, E
   VENZON, D
   MITSUYA, H
   MCINTOSH, K
AF HUSSON, RN
   LAN, Y
   KOJIMA, E
   VENZON, D
   MITSUYA, H
   MCINTOSH, K
TI VERTICAL TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 -
   AUTOLOGOUS NEUTRALIZING ANTIBODY, VIRUS LOAD, AND VIRUS PHENOTYPE
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PERINATAL HIV-1 TRANSMISSION; TO-CHILD TRANSMISSION; MATERNAL
   ANTIBODIES; PROGNOSTIC VALUE; INFECTION; MOTHER; GP120; RISK; INFANT;
   PEPTIDES
AB Objective: To evaluate immunologic and virologic correlates of vertical transmission of human immunodeficiency virus type 1 (HIV-1).
   Design: Case-control study.
   Patients: Women who were prospectively enrolled in a natural history study of HIV-1 infection in women and infants. Sixteen HIV-1-infected women whose infants became infected were matched by CD4(+) cell percentage and use of zidovudine during pregnancy with women whose infants did not become infected.
   Measurements: Maternal autologous neutralizing antibody, virus load determined by RNA-polymerase chain reaction (RNA-PCR), and virus phenotype.
   Results: Most women in both groups had low titers of autologous neutralizing antibody, and no difference in neutralizing titers was observed (range, <4 to 181 in both groups), The HIV-1 copy number in maternal plasma was not significantly different in the two groups but was inversely correlated with maternal CD4(+) cell percentage (p <0.005). Five women in the transmitting group and four in the nontransmitting group had syncytium-inducing (SI) phenotype virus. Two infected infants had SI phenotype virus. The SI phenotype virus was associated with a greater HIV-1 copy number in maternal plasma (p <0.05) and an increase in the mortality rate for the infants (p <0.01).
   Conclusions: In women matched for CD4(+) cell percentage, low titers of autologous neutralizing antibody, high virus load, and SI phenotype virus were not associated with an increased risk of transmission of HIV-1 to their infants.
C1 NCI, MED BRANCH, EXPTL RETROVIROL SECT, BETHESDA, MD 20892 USA.
   NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA.
RP HUSSON, RN (reprint author), HARVARD UNIV, CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DIV INFECT DIS, 300 LONGWOOD AVE, BOSTON, MA 02115 USA.
RI Venzon, David/B-3078-2008
FU NIAID NIH HHS [N01 AI-82507]
NR 40
TC 50
Z9 51
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 1995
VL 126
IS 6
BP 865
EP 871
DI 10.1016/S0022-3476(95)70198-2
PG 7
WC Pediatrics
SC Pediatrics
GA RC754
UT WOS:A1995RC75400002
PM 7776085
ER

PT J
AU TOMAR, SL
   SWANGO, PA
   KLEINMAN, DV
   BURT, BA
AF TOMAR, SL
   SWANGO, PA
   KLEINMAN, DV
   BURT, BA
TI LOSS OF PERIODONTAL ATTACHMENT IN HIV-SEROPOSITIVE MILITARY PERSONNEL
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE PERIODONTAL ATTACHMENT; HIV INFECTION COMPLICATIONS; IMMUNE SYSTEM
   DEFICIENCY
ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; AIDS; INFECTION; DISEASE;
   SMOKING; COHORT; RISK
AB THE CROSS-SECTIONAL RELATIONSHIP between severe loss of periodontal attachment (LPA) and worsening immune status due to HIV infection was evaluated in 474 HIV-infected subjects (416 men, 58 women) aged 18 to 49 years who had been classified at stages 1 through 6 of the Waiter Reed Army Institute of Research (WR) Staging Classification System. LPA was measured at four sites per tooth using a manual probe; severe LPA was defined as greater than or equal to 1 site/subject exhibiting greater than or equal to 5 mm LPA. Severe LPA was found in 94 (20%) of the subjects. Modeling with multiple logistic regression analysis revealed that WR stage and peripheral CD4+ lymphocyte cell counts were not significant independent predictors of severe LPA. Severe LPA was more common in subjects at WR stage 5 or 6 who exhibited oral candidiasis (OC), a marker of immune system damage, than in persons at those WR stages without OC (odds ratio = 7.85; 95% confidence interval (CI) = 1.94-31.81). After the analysis controlled for WR stage, younger subjects receiving AZT had greater odds of severe LPA than same-age subjects not taking the drug (e.g., odds ratio for subjects aged 30 years = 2.59; 95% CI = 1.22, 5.49). Other significant predictors in the model included male sex; retired military status; cigarette smoking; and presence of cratered, ulcerated, or necrotic interdental papillae. HIV-associated immune deficiency may be associated with localized severe LPA, but this may be an indirect association due to medication use, opportunistic infection, or other factors not captured by the WR staging system or peripheral CD4+ cell counts. Comparison with the estimated prevalence of HIV-associated periodontitis (HIV-P) in this population suggests that infected persons may experience severe LPA that does not necessarily have the clinical presentation of HIV-P.
C1 NIDR,BETHESDA,MD 20892.
   UNIV MICHIGAN,SCH PUBL HLTH,PROGRAM DENT PUBL HLTH,ANN ARBOR,MI 48109.
FU NIDCR NIH HHS [T32 DE 07157]
NR 25
TC 34
Z9 35
U1 0
U2 0
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 JUN
PY 1995
VL 66
IS 6
BP 421
EP 428
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA RH251
UT WOS:A1995RH25100001
PM 7562330
ER

PT J
AU NOWJACKRAYMER, RE
   SELWITZ, RH
   KINGMAN, A
   DRISCOLL, WS
AF NOWJACKRAYMER, RE
   SELWITZ, RH
   KINGMAN, A
   DRISCOLL, WS
TI THE PREVALENCE OF DENTAL FLUOROSIS IN A SCHOOL-BASED PROGRAM OF FLUORIDE
   MOUTHRINSING, FLUORIDE TABLETS, AND BOTH PROCEDURES COMBINED
SO JOURNAL OF PUBLIC HEALTH DENTISTRY
LA English
DT Article
DE CARIES PREVENTION; FLUORIDE TABLETS; FLUORIDE MOUTHRINSES; FLUOROSIS;
   PUBLIC HEALTH DENTISTRY
ID CARIES; WATER; EXPOSURE; ENAMEL; CHILDREN; AREAS
AB Objectives: The objective of the study was to describe and compare the prevalence and severity of dental fluorosis in children who participated in an eight-year clinical trial of the effectiveness of school-based fluoride procedures according to three treatment regimens and age of regimen initiation. Methods: At baseline in 1981, 1,640 kindergarten and first grade children residing in a fluoride-deficient community (Springfield, OH) were assigned randomly to a group that (I) rinsed once a week with a 0.2 percent neutral NaF solution; (2) chewed, rinsed, and swallowed daily a neutral 2.2 mg NaF tablet; or (3) carried out both procedures. DMFS examinations were conducted at baseline and after two, five, and eight years of treatment. As a follow-up in 1992, fluorosis examinations using Dean's index were conducted on 448 remaining subjects. Results: Overall, the prevalence of fluorosis was 4.4 percent with 20 children classified as having some definitive level of the condition. No statistically significant differences existed in the,prevalence or severity of fluorosis: (1) among the preventive regimens; (2) among children who began the regimens at ages 5, 6, or 7; or (3) by eruptive status of teeth. Conclusion: These results reiterate the safety of school-based fluoride mouthrinse, fluoride tablet, or combined regimens in communities with fluoride-deficient water supplies.
RP NOWJACKRAYMER, RE (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,NATCHER BLDG,ROOM 3AN-38B,45 CTR DR,MSC 6401,BETHESDA,MD 20892, USA.
NR 34
TC 6
Z9 7
U1 1
U2 2
PU AAPHD NATIONAL OFFICE
PI RICHMOND
PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235
SN 0022-4006
J9 J PUBLIC HEALTH DENT
JI J. Public Health Dent.
PD SUM
PY 1995
VL 55
IS 3
BP 165
EP 170
DI 10.1111/j.1752-7325.1995.tb02361.x
PG 6
WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
   Health
SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
   Health
GA RM097
UT WOS:A1995RM09700008
PM 7562730
ER

PT J
AU STAGER, SV
   LUDLOW, CL
   GORDON, CT
   COTELINGAM, M
   RAPOPORT, JL
AF STAGER, SV
   LUDLOW, CL
   GORDON, CT
   COTELINGAM, M
   RAPOPORT, JL
TI FLUENCY CHANGES IN PERSONS WHO STUTTER FOLLOWING A DOUBLE-BLIND TRIAL OF
   CLOMIPRAMINE AND DESIPRAMINE
SO JOURNAL OF SPEECH AND HEARING RESEARCH
LA English
DT Article
DE CLOMIPRAMINE; DESIPRAMINE; STUTTERING; SEROTONIN; NORADRENALINE
ID OBSESSIVE-COMPULSIVE DISORDER; PANIC DISORDER; ACOUSTIC LRT; STUTTERERS;
   NONSTUTTERERS; HALOPERIDOL; FLUVOXAMINE; SEROTONIN; PLACEBO
AB This study compared fluency changes in adult developmental stuttering speakers treated with two tricyclic antidepressants, clomipramine and desipramine.  Clomipramine is primarily a serotonergic reuptake inhibitor, and desipramine, primarily a noradrenergic reuptake inhibitor.  Sixteen subjects who stuttered participated in a single-blind placebo, double-blind active drug crossover study lasting 12 weeks.  Speech rate and percent fluency did not significantly improve in placebo compared to baseline.  Speech rate significantly increased while repeating, reading or constructing sentences, and during a telephone conversation, but no significant changes in percent fluency were found under clomipramine compared to placebo.  Speech rate during a telephone conversation and percent fluency while speaking in front of an audience of four to seven listeners significantly increased under clomipramine compared to desipramine.  No significant improvements in percent fluency or speech rate were found for any speaking task under desipramine compared to placebo.  Twelve of 16 subjects reported improved fluency compared to baseline using clomipramine, whereas 6 reported improvement using desipramine.  Because more evidence of improvement was found under clomipramine compared to desipramine, fluency improvement may be related to clomipramine's greater selectivity for serotonergic reuptake inhibition.
C1 NIMH,CHILD PSYCHOL BRANCH,BETHESDA,MD 20892.
RP STAGER, SV (reprint author), NIDOCD,VOICE & SPEECH SECT,BLDG 10,ROOM 5D38,10 CTR DR,MSC 1416,BETHESDA,MD 20892, USA.
OI Stager, Sheila/0000-0002-4294-2114; Ludlow, Christy/0000-0002-2015-6171
NR 50
TC 14
Z9 15
U1 1
U2 3
PU AMER SPEECH-LANG-HEARING ASSN
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE RD, ROCKVILLE, MD 20852-3279
SN 0022-4685
J9 J SPEECH HEAR RES
JI J. Speech Hear. Res.
PD JUN
PY 1995
VL 38
IS 3
BP 516
EP 525
PG 10
WC Language & Linguistics; Rehabilitation
SC Linguistics; Rehabilitation
GA RC954
UT WOS:A1995RC95400001
PM 7674643
ER

PT J
AU EVANSSTORMS, RB
   CIDLOWSKI, JA
AF EVANSSTORMS, RB
   CIDLOWSKI, JA
TI REGULATION OF APOPTOSIS BY STEROID-HORMONES
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article; Proceedings Paper
CT IX International Congress on Hormonal Steroids
CY SEP 24-29, 1994
CL DALLAS, TX
ID PROGRAMMED CELL-DEATH; INTERNUCLEOSOMAL DNA FRAGMENTATION;
   DEXAMETHASONE-INDUCED APOPTOSIS; GENE-EXPRESSION; DEPENDENT
   ENDONUCLEASE; IMMATURE THYMOCYTES; RAT THYMOCYTES; C-MYC; GLUCOCORTICOID
   INHIBITION; REGRESSING LIVER
AB Steroid hormones play major roles in regulation of growth, development, homeostasis, and cell death. Together with other hormones and growth factors, steroids regulate both the function and cellular composition of organs throughout the body. In this article we will discuss the mechanisms of steroid hormone regulated apoptosis. Emphasis will be placed on the effect of glucocorticoids on lymphoid cells.
RP EVANSSTORMS, RB (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA.
FU NCI NIH HHS [CA 65049]; NIDDK NIH HHS [DK 32460]
NR 75
TC 75
Z9 75
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid. Biochem. Mol. Biol.
PD JUN
PY 1995
VL 53
IS 1-6
BP 1
EP 8
DI 10.1016/0960-0760(95)00034-W
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA RL314
UT WOS:A1995RL31400001
PM 7626441
ER

PT J
AU DUFAU, ML
   TSAIMORRIS, CH
   HU, ZZ
   BUCZKO, E
AF DUFAU, ML
   TSAIMORRIS, CH
   HU, ZZ
   BUCZKO, E
TI STRUCTURE AND REGULATION OF THE LUTEINIZING-HORMONE RECEPTOR GENE
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article; Proceedings Paper
CT IX International Congress on Hormonal Steroids
CY SEP 24-29, 1994
CL DALLAS, TX
ID LUTROPIN-CHORIOGONADOTROPIN RECEPTOR; TRANSCRIPTION; INITIATOR; CLONING;
   DOMAIN; CDNA
AB Studies of the mechanisms controlling the expression of the rat luteinizing hormone receptor gene were pursued by characterization of the gene structure and identification of regulatory protein binding domains in the 5'-non-coding region of the gene and of 3' non-coding functional domains responsible for generation of the major mRNA forms. The coding region of the rat LHR gene contains 10 introns and 11 exons, of which the first 10 exons comprise the hormone binding extracellular domain and exon 11, the seven transmembrane/G protein coupling module. Several alternative spliced variants of the LHR were identified that conform to deletions of complete and/or partial exons. Within the 6.2 kb of the 3'-non-coding region, two functional LBR pA domains (H1) and (H2) produce two sets of major mRNA transcripts, each coding for both holoreceptor and the form B splice variant. The H1 pA domain is unique to LHR and may represent a recombinant insertion domain. The functional efficiency of each pA domain is related to the specific pA signals, distal downstream elements, and tissue-specific factors. A TATA-less promoter region is present within the 173 bp 5' flanking region of the gene, with Initiator (Inr) elements at transcriptional start sites. Transcription is dependent on the binding of the Sp1 protein at two Sp1 domains that each contribute equally to transcript initiation. Promoter activity is regulated by at least three additional DNA domains, R (-1266 to -1307 bp), C-box (-42 to -73 bp) and M1 (-24 to -42 bp) that bind multiple trans-factors in a tissue-specific manner. Basal promoter activity is enhanced by a functional M1 domain in LHR-expressing mouse Leydig tumor cells (MLTC) but not in nonexpressing CHO cells. C-box binding factors either inhibit promoter activity or block inhibition through overlapping but not identical DNA binding domains that carry AP-2 and NF-1 elements. Removal of the AP-2 element within the C-box results in MLTC-specific transcriptional activation that may involve an MTLC M1/C-box interaction. In addition, competition for C-box factors by an upstream regulatory element (R) that is only inhibitory in CHO cells, indicates that both C-box binding factors compete for this upstream (R) domain in a tissue-specific manner. Competition between the inhibitory and neutral DNA binding factors within both upstream (R) and promoter domains (C-box) could provide a mechanism for the control of LH receptor gene expression in gonadal cells. These studies have revealed a complex pattern of transcriptional regulation that may reflect targets for signal-regulated changes in LH receptor gene expression.
RP DUFAU, ML (reprint author), NIH,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892, USA.
NR 19
TC 20
Z9 23
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid. Biochem. Mol. Biol.
PD JUN
PY 1995
VL 53
IS 1-6
BP 283
EP 291
DI 10.1016/0960-0760(95)00115-G
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA RL314
UT WOS:A1995RL31400042
PM 7626469
ER

PT J
AU NOTTELMANN, ED
   JENSEN, PS
AF NOTTELMANN, ED
   JENSEN, PS
TI BIPOLAR AFFECTIVE-DISORDER IN CHILDREN AND ADOLESCENTS
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
RP NOTTELMANN, ED (reprint author), NIMH,DIV CLIN & TREATMENT RES,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROCKVILLE,MD 20857, USA.
OI Jensen, Peter/0000-0003-2387-0650
NR 5
TC 16
Z9 17
U1 0
U2 1
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 1995
VL 34
IS 6
BP 705
EP 708
PG 4
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA QZ536
UT WOS:A1995QZ53600009
PM 7608042
ER

PT J
AU KANT, AK
   SCHATZKIN, A
   ZIEGLER, RG
AF KANT, AK
   SCHATZKIN, A
   ZIEGLER, RG
TI DIETARY DIVERSITY AND SUBSEQUENT CAUSE-SPECIFIC MORTALITY IN THE
   NHANES-I EPIDEMIOLOGIC FOLLOW-UP-STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
LA English
DT Article
DE DIETARY VARIETY; DIET QUALITY; MORTALITY; CARDIOVASCULAR DISEASE;
   CANCER; NHEFS; NHANES I
ID UNITED-STATES POPULATION; NUTRITION; VARIETY; MEN
AB Objectives: Human diets tend to be complex mixtures of foods and nutrients. Therefore, we examined the relation of a measure of overall diet quality (independent of intake of individual foods or nutrients) with mortality from cardiovascular disease (CVD), cancer, and non-CVD, non-cancer (other) causes.
   Methods: We used data from the NHANES I Epidemiologic follow-up study (n = 10,337; median follow-up time = 14 years; age 25-74 years at baseline), and included 988 CVD, 571 cancer, and 910 other cases. The 24-hour dietary recalls obtained at baseline were scored for quality using a dietary diversity score (DDS). The DDS (range 0-5) counts the number of major food groups-dairy, meat, grain, fruit, and vegetable consumed daily.
   Results: Age-adjusted risk of mortality from all three causes (except cancer in women) was inversely related with DDS in both men and women. Adjustment for multiple covariates attenuated the relative risk estimates slightly for CVD and cancer mortality, but markedly for other mortality.
   Conclusions: The results are suggestive of an increased risk of CVD and cancer mortality associated with diets characterized by omission of several major food groups.
C1 NCI,BETHESDA,MD 20892.
RP KANT, AK (reprint author), CUNY QUEENS COLL,FLUSHING,NY 11367, USA.
NR 22
TC 107
Z9 108
U1 2
U2 7
PU AMER COLL NUTRITION
PI NEW YORK
PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003
SN 0731-5724
J9 J AM COLL NUTR
JI J. Am. Coll. Nutr.
PD JUN
PY 1995
VL 14
IS 3
BP 233
EP 238
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA RB237
UT WOS:A1995RB23700007
PM 8586771
ER

PT J
AU GRECO, AV
   TATARANNI, PA
   MINGRONE, G
   DEGAETANO, A
   MANTO, A
   COTRONEO, P
   GHIRLANDA, G
AF GRECO, AV
   TATARANNI, PA
   MINGRONE, G
   DEGAETANO, A
   MANTO, A
   COTRONEO, P
   GHIRLANDA, G
TI DAILY ENERGY-METABOLISM IN PATIENTS WITH TYPE-1 DIABETES-MELLITUS
SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
LA English
DT Article
DE TYPE 1 DIABETES; ENERGY EXPENDITURE; INDIRECT CALORIMETRY; RESPIRATION
   CHAMBER
ID INDIRECT CALORIMETRY; DIET COMPOSITION; FAT OXIDATION; OBESE WOMEN;
   EXPENDITURE; CARBOHYDRATE; GLUCOSE; THERMOGENESIS; EXERCISE; BALANCE
AB Objective: We evaluated the daily energy balance and main substrate utilization in Type 1 insulin dependent diabetic patients and healthy volunteers.
   Methods: Ten patients with Type 1 diabetes mellitus and eight healthy volunteers were studied. Diabetic patients were well controlled under intensive insulin treatment (0.6 UI/kg body weight, HbA(1c) = 5.5 +/- 0.7%). During the 30 hours each subject spent in the respiration chamber VO2, VCO2, respiratory quotient, daily energy intake, 24-hour, day-time, night-time and basal energy expenditure as well as energy expenditure during exercise tar 40% maximal exercise capacity), main substrate oxidation (carbohydrates, lipids and proteins) and overall diet-induced thermogenesis, were measured. The results were corrected for 24-hour urinary nitrogen loss.
   Results: Diet-induced thermogenesis, expressed as percent of energy intake, was found to be significantly lower in diabetic patients than in control subjects (6.69 +/- 1.29% vs 11.8 +/- 4.71% of energy intake, p < 0.05). A negative correlation was found between diet-induced thermogenesis and daily average glycemia for diabetic patients (r = -0.65, p < 0.01). Energy expenditure during exercise, calculated in terms of net work efficiency, was not different between the two groups.
   Conclusions: In conclusion, since diet-induced thermogenesis is highly correlated with the theoretical cost of glucose storage and since no difference was found in carbohydrate oxidation, glucose storage in diabetic patients is probably reduced when hyperglycemia occurs. Diabetic patients in good metabolic control are able to perform mild exercise with a work efficiency very similar to that of control subjects.
C1 NIDDK, CLIN DIABET & NUTR SECT, PHOENIX, AZ USA.
   UNIV CATTOLICA SACRO CUORE, DEPT GEN SURG, NATL RES CTR, I-00168 ROME, ITALY.
RP GRECO, AV (reprint author), UNIV CATTOLICA SACRO CUORE, DEPT INTERNAL MED, LGO A GEMELLI 8, I-00168 ROME, ITALY.
NR 26
TC 8
Z9 8
U1 0
U2 4
PU AMER COLL NUTRITION
PI NEW YORK
PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003
SN 0731-5724
J9 J AM COLL NUTR
JI J. Am. Coll. Nutr.
PD JUN
PY 1995
VL 14
IS 3
BP 286
EP 291
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA RB237
UT WOS:A1995RB23700015
PM 8586779
ER

PT J
AU WATSON, MR
   BROWN, LJ
AF WATSON, MR
   BROWN, LJ
TI THE ORAL HEALTH OF UNITED-STATES HISPANICS - EVALUATING THEIR NEEDS AND
   THEIR USE OF DENTAL SERVICES
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
ID TOTAL TOOTH LOSS; MEXICAN-AMERICANS; PERIODONTAL-DISEASE; SOUTHWESTERN
   HHANES; CARE; ACCESS; ACCULTURATION; PREVALENCE; CARIES; ADULTS
AB Data from the 1985-1986 National Survey of Oral Health in U.S. Adults and Seniors showed that the oral health of Hispanic American adults and seniors was comparable to that of black adults and seniors.  White adults and seniors had better oral health than their minority counterparts for all measures observed and were better able to afford dental care.
C1 BALTIMORE VET AFFAIRS MED CTR,BALTIMORE,MD.
   NIDR,DIV EPIDEMIOL,BETHESDA,MD 20892.
   NIDR,ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892.
RP WATSON, MR (reprint author), UNIV MARYLAND,SCH DENT,666 W BALTIMORE ST,BALTIMORE,MD 21201, USA.
NR 22
TC 17
Z9 17
U1 0
U2 0
PU AMER DENTAL ASSN
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611
SN 0002-8177
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD JUN
PY 1995
VL 126
IS 6
BP 789
EP 795
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA RC144
UT WOS:A1995RC14400016
PM 7797736
ER

PT J
AU SNYDER, MP
   MONTGOMERY, D
   OBARZANEK, E
   NICKLAS, T
AF SNYDER, MP
   MONTGOMERY, D
   OBARZANEK, E
   NICKLAS, T
TI TAKING THE FAT OUT OF SCHOOL LUNCH PROGRAMS - REPLY
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Letter
C1 UNIV TEXAS,AUSTIN,TX 78712.
   NHLBI,BETHESDA,MD 20892.
   TULANE UNIV,NEW ORLEANS,LA 70118.
RP SNYDER, MP (reprint author), UNIV MINNESOTA,MINNEAPOLIS,MN 55455, USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER DIETETIC ASSN
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD JUN
PY 1995
VL 95
IS 6
BP 644
EP 646
DI 10.1016/S0002-8223(95)00174-3
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA RB309
UT WOS:A1995RB30900003
ER

PT J
AU SIMPSON, JT
   TOROK, DS
   MARKEY, SP
AF SIMPSON, JT
   TOROK, DS
   MARKEY, SP
TI PENTAFLUOROBENZYL CHLOROFORMATE DERIVATIZATION FOR ENHANCEMENT OF
   DETECTION OF AMINO-ACIDS OR ALCOHOLS BY ELECTRON-CAPTURE NEGATIVE-ION
   CHEMICAL-IONIZATION MASS-SPECTROMETRY
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Note
AB Pentafluorobenzyl chloroformate (PFB-chloroformate) has been utilized as a derivatization reagent to impart electron affinity and provide structurally relevant fragmentation in electron capture negative ion chemical ionization mass spectrometry (ECNICI-MS). Phenylalanine (Phe) and decanol were used as model analytes. The conditions used for their derivatization and the chromatographic and mass spectrometric properties of the derivatives are reported. Phenylalanine in aqueous solution was derivatized in one step by using PFB-chloroformate and a mixture of water, ethanol, and pyridine. The phenylalanine N-pentafluorobenzyl-oxycarbonyl ethyl ester (N-PFBC-Phe-OEt) exhibited good gas chromatographic properties and in ECNICI-MS, a dominant [M - 181](-) fragment carries most of the ion current. Selected ion monitoring experiments on N-PFBC-Phe-OEt resulted in the facile detection of 400 fmol of material. Decanol was derivatized by using anhydrous conditions, and the resultant pentafluorobenzyl carbonate also exhibited a predominant [M - 181](-) ion in ECNICI-MS. Initial results indicate that the ECNICI-MS molar response of the decyl pentafluorobenzyl carbonate derivative is six-fold that of the decyl pentafluorobenzoate.
C1 NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892.
NR 11
TC 24
Z9 24
U1 1
U2 10
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD JUN
PY 1995
VL 6
IS 6
BP 525
EP 528
DI 10.1016/1044-0305(95)00231-2
PG 4
WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA RC723
UT WOS:A1995RC72300010
PM 24214307
ER

PT J
AU KLAHR, S
   BREYER, JA
   BECK, GJ
   DENNIS, VW
   HARTMAN, JA
   ROTH, D
   STEINMAN, TI
   WANG, SR
   YAMAMOTO, ME
AF KLAHR, S
   BREYER, JA
   BECK, GJ
   DENNIS, VW
   HARTMAN, JA
   ROTH, D
   STEINMAN, TI
   WANG, SR
   YAMAMOTO, ME
TI DIETARY-PROTEIN RESTRICTION, BLOOD-PRESSURE CONTROL, AND THE PROGRESSION
   OF POLYCYSTIC KIDNEY-DISEASE
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
DE KETO ACID AMINO ACID SUPPLEMENT; GLOMERULAR DISEASE; GFR; CLINICAL
   TRIALS
ID RENAL-FAILURE; CONVERTING ENZYME; HYPERTENSION; PROGNOSIS;
   MANIFESTATIONS; MANAGEMENT; INHIBITION; TRIAL
AB In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m(2), neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m(2), assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.
C1 NIDDKD,BETHESDA,MD 20892.
NR 47
TC 129
Z9 131
U1 0
U2 4
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUN
PY 1995
VL 5
IS 12
BP 2037
EP 2047
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA RC959
UT WOS:A1995RC95900012
PM 7579052
ER

PT J
AU YANAGAWA, T
   FUJII, Y
AF YANAGAWA, T
   FUJII, Y
TI PROJECTION-METHOD MANTEL-HAENSZEL ESTIMATOR FOR K-2XJ TABLES
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE CASE-CONTROL STUDY; DUALLY CONSISTENT; EPIDEMIOLOGY; ODDS RATIO
   ESTIMATION; SPARSE DATA
AB A projection method is introduced to generalize the Mantel-Haenszel estimator for estimating the common odds ratios in K2 x J (J > 2) tables. The method provides estimators in an explicit form and needs no iterative computation. It is shown that the generalized Mantel-Haenszel estimator proposed by Greenland, and Yanagawa and Fujii is obtained by this method as a special case. Furthermore, selecting appropriate weight, it is shown that the method leads to an estimator that is asymptotically equivalent to the generalized Mantel-Haenszel estimator proposed by Liang. A dually consistent estimator of the variance of the estimator is proposed. The characteristics of these estimators have been evaluated by Monte Carlo means.
C1 MIYAZAKI UNIV,FAC EDUC,DEPT MATH,MIYAZAKI 88921,JAPAN.
   NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709.
RP YANAGAWA, T (reprint author), KYUSHU UNIV,DEPT MATH,FUKUOKA 812,JAPAN.
NR 18
TC 6
Z9 6
U1 0
U2 1
PU AMER STATIST ASSN
PI ALEXANDRIA
PA 1429 DUKE ST, ALEXANDRIA, VA 22314
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 1995
VL 90
IS 430
BP 649
EP 656
PG 8
WC Statistics & Probability
SC Mathematics
GA RA104
UT WOS:A1995RA10400032
ER

PT J
AU LEGLER, JM
   LEFKOPOULOU, M
   RYAN, LM
AF LEGLER, JM
   LEFKOPOULOU, M
   RYAN, LM
TI EFFICIENCY AND POWER OF TESTS FOR MULTIPLE BINARY OUTCOMES
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE GENERALIZED ESTIMATING EQUATIONS; MULTIPLE BINARY END-POINTS; PITMAN
   ASYMPTOTIC RELATIVE EFFICIENCIES; SCORE TESTS
ID LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; CLINICAL-TRIALS;
   BIRTH-DEFECTS; ENDPOINTS; MALFORMATIONS; ASSOCIATIONS; DESIGN
AB Global tests provide a useful tool for comparing two or more groups with respect to multiple correlated outcomes. We adapt and compare the performance of tests that have been suggested for use with multiple continuous outcomes to the case of multiple binary outcomes. Comparisons and guidelines are based on asymptotic relative efficiencies (ARE's) and simulations. These results are illustrated using an application from teratology. We extend the work of Lefkopoulou and Ryan to include general M-group comparisons alternatives where group effects may differ for each outcome. A concise form for this general class of score tests is derived. To compute the ARE's for this class of tests, we devise a useful characterization of the alternative space based on multivariate polar coordinates. Our findings indicate that the common outcome effect tests are efficient for a remarkably large range of circumstances. A simple formula applies to compute the maximum number of unaffected outcomes that can be included in a set of outcomes for which the common outcome effect tests remain more efficient than those derived under multidimensional alternatives. For comparison, other global tests are also considered in the simulations: two tests based on resampling( maximal and minimal z tests), a rank-sum test, a generalized least squares test, and a test based on collapsing multiple endpoints to a single binary outcome. Besides the common outcome effect tests, the resampling tests and the rank-sum test are found to perform very well for the cases under consideration.
C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115.
RP LEGLER, JM (reprint author), NICHHD,BETHESDA,MD 20892, USA.
RI Ryan, Louise/A-4562-2009
OI Ryan, Louise/0000-0001-5957-2490
NR 30
TC 32
Z9 32
U1 0
U2 3
PU AMER STATIST ASSN
PI ALEXANDRIA
PA 1429 DUKE ST, ALEXANDRIA, VA 22314
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 1995
VL 90
IS 430
BP 680
EP 693
PG 14
WC Statistics & Probability
SC Mathematics
GA RA104
UT WOS:A1995RA10400035
ER

PT J
AU STRIKER, GE
AF STRIKER, GE
TI KUH NOTES - UROLOGY RESEARCH INCENTIVES FOR THE BASIC SCIENTIST AND
   PHYSICIAN
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
DE GOVERNMENT AGENCIES; EDUCATION, MEDICAL
RP STRIKER, GE (reprint author), NIDDKD,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 1995
VL 153
IS 6
BP 1951
EP 1951
DI 10.1016/S0022-5347(01)67367-1
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA QX369
UT WOS:A1995QX36900067
PM 7752366
ER

PT J
AU WALTHER, MM
   GNARRA, JR
   ELWOOD, L
   XU, HJ
   FLORENCE, C
   ANGLARD, P
   HU, SX
   KING, C
   TRAHAN, E
   HURLEY, K
   SENS, D
   VENZON, D
   LIU, S
   JAFFE, GS
   BENEDICT, WF
   LINEHAN, WM
AF WALTHER, MM
   GNARRA, JR
   ELWOOD, L
   XU, HJ
   FLORENCE, C
   ANGLARD, P
   HU, SX
   KING, C
   TRAHAN, E
   HURLEY, K
   SENS, D
   VENZON, D
   LIU, S
   JAFFE, GS
   BENEDICT, WF
   LINEHAN, WM
TI LOSS OF HETEROZYGOSITY OCCURS CENTROMERIC TO RB WITHOUT ASSOCIATED
   ABNORMALITIES IN THE RETINOBLASTOMA GENE IN TUMORS FROM PATIENTS WITH
   METASTATIC RENAL-CELL CARCINOMA
SO JOURNAL OF UROLOGY
LA English
DT Article
DE RETINOBLASTOMA; GENE EXPRESSION; CARCINOMA, RENAL CELL
ID VONHIPPEL-LINDAU DISEASE; SUSCEPTIBILITY GENE; LUNG-CANCER; ALTERED
   EXPRESSION; SUPPRESSOR GENE; BLADDER-CANCER; OSTEO-SARCOMA; PROTEIN;
   INACTIVATION; IDENTIFICATION
AB Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RE) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic, renal cell carcinoma.
   Three of fifteen (20%) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RE gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32%) informative cell lines had LOH centromeric to the RE gene at the D13S1 locus, No LOH (0 of 7) was seen telomeric to the RE gene at the D13S2 locus. None of the 28 cell lines examined had decreased RE mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and unphosphorylated forms of RE protein of expected molecular weight in all 41 cell lines (33 primary and 8 metastatic) examined. Twenty-nine primary cell lines and 6 metastatic cell lines all demonstrated normal immunohistochemical staining. Loss of RE immunohistochemical staining in paraffin-embedded tissue was detected in none of the primary tumors (0 of 30) or metastatic tumors (0 of 12). The absence of abnormalities of RE expression detected in these renal cell carcinomas suggests that abnormalities of the RB gene are not central to malignant transformation or progression in this tumor type; however, another tumor suppressor gene centromeric to the RB locus may be important in renal cell carcinogenesis.
C1 NCI,DCT,COP,DATA MANAGEMENT SECT,PATHOL BRANCH,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892.
   MED UNIV S CAROLINA,DEPT PATHOL,CHARLESTON,SC 29425.
   BAYLOR COLL MED,CTR BIOTECHNOL,THE WOODLANDS,TX.
RP WALTHER, MM (reprint author), NCI,DCT,COP,BIOSTAT SECT,PATHOL BRANCH,SURG BRANCH,UROL ONCOL SECT,BLDG 10,ROOM 2B43,BETHESDA,MD 20892, USA.
RI Venzon, David/B-3078-2008
FU NCI NIH HHS [CA-54672]
NR 50
TC 20
Z9 20
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 JUN
PY 1995
VL 153
IS 6
BP 2050
EP 2054
DI 10.1016/S0022-5347(01)67400-7
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA QX369
UT WOS:A1995QX36900100
PM 7752392
ER

PT J
AU GOLDING, B
   INMAN, J
   HIGHET, P
   BLACKBURN, R
   MANISCHEWITZ, J
   BLYVEIS, N
   ANGUS, RD
   GOLDING, H
AF GOLDING, B
   INMAN, J
   HIGHET, P
   BLACKBURN, R
   MANISCHEWITZ, J
   BLYVEIS, N
   ANGUS, RD
   GOLDING, H
TI BRUCELLA-ABORTUS CONJUGATED WITH A GP120 OR V3 LOOP PEPTIDE DERIVED FROM
   HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 INDUCES NEUTRALIZING ANTI-HIV
   ANTIBODIES, AND THE V3 B-ABORTUS CONJUGATE IS EFFECTIVE EVEN AFTER
   CD4(+) T-CELL DEPLETION
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INDEPENDENT TYPE-1; IFN-GAMMA; RESPONSES; VACCINES; KINETICS; PROTEINS;
   CARRIER; INVITRO
AB Human immunodeficiency virus type 1 (HIV-1) infection is associated with loss of function and numbers of CD4(+) T-helper cells, In order to bypass the requirement for CD4(+) cells in antibody responses, we have utilized heat-inactivated Brucella abortus as a carrier, In this study we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 of 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF2 to B. abortus [gp120(SF2)-B, abortus]. Our results showed that specific antibody responses, dominated by immunoglobulin G2a in BALB/c mice, were induced by these conjugates, Sera from the immunized mice bound native gp120 expressed on the surfaces of cells infected with a recombinant vaccinia virus gp160 vector (VPE16), Sera from mice immunized with gp120(SF2)-B, abortus inhibited binding of soluble CD4 to gp120, whereas sera from mice immunized with V3-B, abortus were ineffective, Sera from mice immunized with either conjugate were capable of blocking syncytium formation between CD4(+) CEM cells and H9 cells chronically infected dth the homologous virus, Sera from mice immunized with gp120(SF2)-B. abortus were more potent than sera from mice immunized with V3-B. abortus in inhibiting syncytia from heterologous HIV-1 laboratory strains, Importantly, in primary and secondary responses, V3-B. abortus evoked anti-HN MN antibodies in mice depleted of CD4(+) cells, and sera from these mice were able to inhibit syncytia, These findings indicate that B, abortus can provide carrier function for peptides and proteins from HIV-1 and suggest that they could be used for immunization of individuals with compromised CD4(+) T-cell function.
C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,RETROVIRUS RES LAB,BETHESDA,MD 20892.
   NIAID,BETHESDA,MD 20892.
   USDA,ANIM & PLANT HLTH INSPECT SERV,VET SERV,NATL VET SERV LABS,AMES,IA 50010.
RP GOLDING, B (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,8800 ROCKVILLE PK,BETHESDA,MD 20892, USA.
NR 26
TC 23
Z9 23
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 JUN
PY 1995
VL 69
IS 6
BP 3299
EP 3307
PG 9
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100007
PM 7745677
ER

PT J
AU NUSSBAUM, O
   BRODER, CC
   MOSS, B
   STERN, LBL
   ROZENBLATT, S
   BERGER, EA
AF NUSSBAUM, O
   BRODER, CC
   MOSS, B
   STERN, LBL
   ROZENBLATT, S
   BERGER, EA
TI FUNCTIONAL AND STRUCTURAL INTERACTIONS BETWEEN MEASLES-VIRUS
   HEMAGGLUTININ AND CD46
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CANINE-DISTEMPER VIRUS; MEMBRANE COFACTOR PROTEIN; BACTERIOPHAGE-T7
   RNA-POLYMERASE; VACCINIA VIRUS; MONOCLONAL-ANTIBODIES; FUSION PROTEIN;
   EXPRESSION SYSTEM; GLYCOPROTEINS; PURIFICATION; RECEPTOR
AB We analyzed the roles of the individual measles virus (MV) surface glycoproteins in mediating functional and structural interactions with human CD46, the primary MV receptor. On one cell population, recombinant vaccinia virus vectors were used to produce the MV hemagglutinin (II) and fusion (F) glycoproteins. As fusion partner cells, various cell types were examined, without or with human CD46 (endogenous or recombinant vaccinia virus encoded), Fusion between the two cell populations was monitored by a quantitative reporter gene activation assay and by syncytium formation, MV glycoproteins promoted fusion with primate cells but not with nonprimate cells; recombinant CD46 rendered nonprimate cells competent for MV glycoprotein-mediated fusion, Markedly different fusion specificity was observed for another morbillivirus, canine distemper virus (CDV): recombinant CDV glycoproteins promoted fusion with primate and nonprimate cells independently of CD46. Fusion by the recombinant MV and CDV glycoproteins required coexpression of H plus F in either homologous or heterologous combinations. To assess the role of H versus F in determining the CD46 dependence of MV fusion, we examined the fusion specificities of cells producing heterologous glycoprotein combinations, The specificity of H-MV plus F-CDV paralleled that observed for the homologous MV glycoproteins: fusion occurred with primate cells but not with nonprimate cells unless they produced recombinant CD46. By contrast, the specificity of H-CDV plus F-MV paralleled that for the homologous CDV glycoproteins: fusion occurred with either primate or nonprimate cells with no dependence on CD46. Thus, for both MV and CDV; fusion specificity was determined by H. In particular, the results demonstrate a functional interaction between H-MV and CD46, Flow cytometry and antibody coprecipitation studies provided a structural correlate to this functional interation: CD46 formed a molecular complex with H-MV but not with F-MV or with either CDV glycoprotein. These results highlight the critical role of the H glycoprotein in determining MV spectificity for CD46-positive cells.
C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892.
   TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT MOLEC MICROBIOL & BIOTECHNOL,IL-69978 TEL AVIV,ISRAEL.
NR 63
TC 53
Z9 53
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 JUN
PY 1995
VL 69
IS 6
BP 3341
EP 3349
PG 9
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100012
PM 7745681
ER

PT J
AU WONDERLING, RS
   KYOSTIO, SRM
   OWENS, RA
AF WONDERLING, RS
   KYOSTIO, SRM
   OWENS, RA
TI A MALTOSE-BINDING PROTEIN ADENOASSOCIATED VIRUS REP68 FUSION PROTEIN HAS
   DNA-RNA HELICASE AND ATPASE ACTIVITIES
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INHIBITS CELLULAR-TRANSFORMATION; INVITRO RESOLUTION; TERMINAL REPEAT;
   GENE-PRODUCT; REPLICATION; TYPE-2; IDENTIFICATION; EXPRESSION; GENOME;
   REP78
AB The adeno-associated virus type 2 (AAV) Rep68 protein produced in Escherichia coli as a fusion protein with maltose-binding protein (MBP-Rep68 Delta) has previously been shown to possess DNA-DNA helicase activity, as does the purified wild-type Rep68. In the present study, we demonstrate that MBP-Rep68 Delta also catalyzes the unwinding of a DNA-RNA hybrid, MBP-Rep68 Delta-mediated DNA-RNA helicase activity required ATP hydrolysis and the presence of Mg2+ ions and was inhibited by high ionic strength. The efficiency of the DNA-RNA helicase activity of MBP-Rep68 Delta was comparable to its DNA-DNA helicase activity. However, MBP-Rep68 Delta lacked the ability to unwind a blunt-ended DNA-RNA substrate and RNA-RNA duplexes. We have also demonstrated that MBP-Rep68 Delta has ATPase activity which is enhanced by the presence of single-stranded DNA but not by RNA. The MBP-Rep68 Delta NTP mutant protein, which has a lysine-to-histidine substitution at amino acid 340 in the putative nucleoside triphosphate-binding site of Rep68, not only lacks DNA-RNA helicase and ATPase activities but also inhibits the helicase activity of MBP-Rep68 Delta DNA-RNA helicase activity of Rep proteins might play a pivotal role in the regulation of AAV gene expression by AAV Rep proteins.
C1 NIDDK,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892.
NR 47
TC 58
Z9 58
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 JUN
PY 1995
VL 69
IS 6
BP 3542
EP 3548
PG 7
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100034
PM 7538173
ER

PT J
AU LUSSO, P
   COCCHI, F
   BALOTTA, C
   MARKHAM, PD
   LOUIE, A
   FARCI, P
   PAL, R
   GALLO, RC
   REITZ, MS
AF LUSSO, P
   COCCHI, F
   BALOTTA, C
   MARKHAM, PD
   LOUIE, A
   FARCI, P
   PAL, R
   GALLO, RC
   REITZ, MS
TI GROWTH OF MACROPHAGE-TROPIC AND PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS
   TYPE-1 (HIV-1) ISOLATES IN A UNIQUE CD4(+) T-CELL CLONE (PM1) - FAILURE
   TO DOWN-REGULATE CD4 AND TO INTERFERE WITH CELL-LINE-TROPIC HIV-1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENVELOPE V3 LOOP; HTLV-III LAV; SOLUBLE CD4; MONONUCLEAR PHAGOCYTES;
   NEUTRALIZING EPITOPE; GENOMIC DIVERSITY; MICROGLIAL CELLS; VIRAL
   ENVELOPE; HOST RANGE; INFECTION
AB Human immunodeficiency virus type 1 (HIV-1) isolates derived directly from clinical samples are usually unable to grow in cytokine-independent continuous cell lines, thus hindering the study of their biological features and their sensitivity to humoral and cellular protective immunity. To overcome these limitations, we have derived from the Hut78 T-cell line a CD4(+) clone (PM1) characterized by a unique susceptibility to a wide range of HIV-1 isolates, including primary and biologically pure macrophage (M phi)-tropic isolates (e.g., HIV-1(BaL), which are unable to infect other human T- or promonocytic cell lines, Both primary and M phi-tropic HIV-1 establish persistent infection in PM1, with sustained levels of virus replication for prolonged periods, Experiments with chimeric viruses containing envelope fragments of HIV-1(BaL) inserted into the genetic framework of HXB2, a molecular clone derived from the cell-line-tropic isolate HIV-1(IIIB), showed the third hypervariable domain (V3) of gp 120 to be a critical determinant of the cell line tropism of HIV-1. Nevertheless, the V3 loop of HIV-(BaL), was not sufficient to confer on the chimeras a bona fide M phi tropism. The biological characteristics of HIV-1(BaL) and of a primary isolate (HIV-1(573)) were investigated by using the PM1 clone. Infection of PM1 by HIV-1(BaL) was critically dependent on the CD4 receptor, as shown by competition experiments with an anti-CD4 monoclonal antibody (OKT4a) or with soluble CD4. However, the amount of soluble CD4 required for inhibition of HIV-1(BaL) was approximately 100-fold higher than for HIV-1(IIIB), suggesting that the affinity of HIV-1(BaL) for CD4 is significantly lower, Infection of PM1 with either HIV-1(BaL) or HIV-1(573) failed to induce downregulation of surface CD4 expression and syncytium formation. Analogous results were obtained with a chimeric virus (HXB2[BaLPvuII-BamHI]) encompassing a large portion of gp120 and gp41 of HIV-1(BaL) indicating that the env genes contain critical determinants for CD4 downregulation and syncytium formation. Consistent with the lack of CD4 downregulation, persistent infection of PM1 by HIV-1(BaL) or HIV-1(573) failed to interfere with HIV-1(IIIB) superinfection, as revealed by the expression of a type-specific V3 loop epitope (M77) and by the induction of extensive syncytium formation. This lack of interference suggests that a direct viral interaction may occur in vivo between biologically diverse HIV-1 strains. The PM1 clone represents a reproducible and efficient cellular system for the in vitro propagation of primary and M phi-tropic isolates of HIV-1 and may therefore provide a precious tool for studies aimed at developing broadly active vaccines against HIV-1.
C1 ADV BIOSCI LABS,DEPT CELL BIOL,KENSINGTON,MD 20895.
   UNIV CAGLIARI,DEPT INTERNAL MED,I-09100 CAGLIARI,ITALY.
RP LUSSO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,37 CONVENT DR,BETHESDA,MD 20892, USA.
NR 49
TC 212
Z9 213
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 JUN
PY 1995
VL 69
IS 6
BP 3712
EP 3720
PG 9
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100053
PM 7745720
ER

PT J
AU NAZAROV, V
   WOLFF, L
AF NAZAROV, V
   WOLFF, L
TI NOVEL INTEGRATION SITES AT THE DISTAL 3' END OF THE C-MYB LOCUS IN
   RETROVIRUS-INDUCED PROMONOCYTIC LEUKEMIAS
SO JOURNAL OF VIROLOGY
LA English
DT Note
ID NUCLEOTIDE-SEQUENCE; PROVIRAL INTEGRATION; MYELOID TUMORS; BALB/C MICE;
   ACTIVATION; ONCOGENE; VIRUS; GENE; PROTOONCOGENE; ORGANIZATION
AB In BALB/c nu/nu and sublethally irradiated DBA/2 mice, promonocytic leukemia was induced by intravenous inoculation of Friend murine leukemia virus (F-MuLV) strain C57 in conjunction with intraperitoneal injection of pristane. These tumors appear to be identical morphologically to previously reported ones induced by other MuLVs, such as Moloney, amphotropic 4070A, and F-MuLV FB29, which most commonly have provirus integrations in the 5' end of the c-myb locus. Interestingly, 2 of the 16 F-MuLV-induced tumors had viruses integrated in the distal 3' end of c-myb. To determine the precise locations of these integrations, it was necessary to clone sequences encoding the 3' c-myb exons and to prepare a physical map of this region. Exons 10 to 15 were positioned on the map, and it was found that the proviruses in the aforementioned tumors were located within narrow region in the beginning of the large (greater than 11 kb) intron 14. The predicted protein product encoded by the affected alleles is truncated by 38 amino acids. This represents a novel virus integration site which is most likely associated with oncogenic activation, of the c-myb gene during leukemogenesis.
C1 NCI, GENET LAB, BETHESDA, MD 20892 USA.
NR 25
TC 24
Z9 24
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 JUN
PY 1995
VL 69
IS 6
BP 3885
EP 3888
PG 4
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100076
PM 7745739
ER

PT J
AU GALLINELLA, G
   ANDERSON, SM
   YOUNG, NS
   BROWN, KE
AF GALLINELLA, G
   ANDERSON, SM
   YOUNG, NS
   BROWN, KE
TI HUMAN PARVOVIRUS B19 CAN INFECT CYNOMOLGUS MONKEY MARROW-CELLS IN
   TISSUE-CULTURE
SO JOURNAL OF VIROLOGY
LA English
DT Note
AB The human pathogenic parvovirus B19 cannot be grown in standard tissue culture but propagates in human bone marrow, where it is cytotoxic to erythroid progenitor cells. We now show that parvovirus B19 can replicate in cynomolgus bone marrow. Cynomolgus monkeys may be a suitable animal model for pathogenesis studies of parvovirus B19.
C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892.
NR 10
TC 11
Z9 11
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 JUN
PY 1995
VL 69
IS 6
BP 3897
EP 3899
PG 3
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100079
PM 7745742
ER

PT J
AU FREED, EO
   ENGLUND, G
   MARTIN, MA
AF FREED, EO
   ENGLUND, G
   MARTIN, MA
TI ROLE OF THE BASIC DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MATRIX
   IN MACROPHAGE INFECTION
SO JOURNAL OF VIROLOGY
LA English
DT Note
ID MONONUCLEAR PHAGOCYTES; CELL-TYPES; PROTEIN; HIV-1; GAG; MYRISTOYLATION;
   REPLICATION; REGION; MORPHOGENESIS; REQUIREMENT
AB The matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein contains a highly basic region near its amino terminus. It has been proposed that this basic domain, in conjunction with the HIV-1 accessory protein Vpr, is responsible for the localization of the HIV-1 preintegration complex to the nucleus in nondividing cells. It has also been postulated that the matrix basic domain assists in the targeting of the HIV-1 Gag precursor pr55(Gag) to the plasma membrane during virus assembly. To evaluate the role of this highly basic sequence during infection of primary human monocyte-derived macrophages, single- and double-amino-acid-substitution mutations were introduced, and the effects on virus particle production, Gag protein processing, envelope glycoprotein incorporation into virus particles, and virus infectivity in the CEM(12D-7) T-cell line, peripheral blood mononuclear cells, and primary human monocyte-derived macrophages were analyzed. Although modest effects on virus particle production were observed with some of the mutants, none abolished infectivity in primary human monocyte-derived macrophages. In contrast with previously reported studies involving some of the same matrix basic domain mutants, infectivity in monocyte-derived macrophages was retained even when combined with a vpr mutation.
RP FREED, EO (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 307,BETHESDA,MD 20892, USA.
NR 52
TC 209
Z9 211
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 JUN
PY 1995
VL 69
IS 6
BP 3949
EP 3954
PG 6
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100090
PM 7745752
ER

PT J
AU BREITBURD, F
   KIRNBAUER, R
   HUBBERT, NL
   NONNENMACHER, B
   TRINDINHDESMARQUET, C
   ORTH, G
   SCHILLER, JT
   LOWY, DR
AF BREITBURD, F
   KIRNBAUER, R
   HUBBERT, NL
   NONNENMACHER, B
   TRINDINHDESMARQUET, C
   ORTH, G
   SCHILLER, JT
   LOWY, DR
TI IMMUNIZATION WITH VIRUS-LIKE PARTICLES FROM COTTONTAIL RABBIT
   PAPILLOMAVIRUS (CRPV) CAN PROTECT AGAINST EXPERIMENTAL CRPV INFECTION
SO JOURNAL OF VIROLOGY
LA English
DT Note
ID STRUCTURAL POLYPEPTIDES; CERVICAL-CANCER; BOVINE; L1; VACCINATION;
   PROGRESSION; REGRESSION; PROSPECTS; CARCINOMA; VACCINES
AB We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 x 10(10) and 2 x 10(11) particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection, Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection.
C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892.
   INST PASTEUR,INSERM,U190,UNITE PAPILLOMAVIRUS,F-75724 PARIS,FRANCE.
   UNIV VIENNA,DEPT DERMATOL,DIV IMMUNODERMATOL & INFECT SKIN DIS,A-1090 VIENNA,AUSTRIA.
NR 34
TC 409
Z9 426
U1 0
U2 8
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 JUN
PY 1995
VL 69
IS 6
BP 3959
EP 3963
PG 5
WC Virology
SC Virology
GA QX931
UT WOS:A1995QX93100092
PM 7745754
ER

PT J
AU MYERS, BD
   NELSON, RG
   TAN, M
   BECK, GJ
   BENNETT, PH
   KNOWLER, WC
   BLOUCH, K
   MITCH, WE
AF MYERS, BD
   NELSON, RG
   TAN, M
   BECK, GJ
   BENNETT, PH
   KNOWLER, WC
   BLOUCH, K
   MITCH, WE
TI PROGRESSION OF OVERT NEPHROPATHY IN NON-INSULIN-DEPENDENT DIABETES
SO KIDNEY INTERNATIONAL
LA English
DT Article
ID GLOMERULAR SIZE-SELECTIVITY; CONVERTING ENZYME-INHIBITION; PIMA-INDIANS;
   RENAL-DISEASE; CHARGE SELECTIVITY; BASEMENT-MEMBRANE; NEPHROTIC HUMANS;
   FILTRATION RATE; MELLITUS; KIDNEY
AB The detection of overt albuminuria (> 300 mg/g creatinine) in the absence of azotemia was used to diagnose early nephropathy in 34 Pima Indians with NIDDM of 16 +/- 1 years duration. Differential solute clearances were performed serially to define the course of the glomerular injury over 48 months. At baseline, the GFR (107 +/- 5 ml/min), filtration fraction and sieving coefficients of relatively permeant dextrans (< 52 Angstrom) were all depressed below corresponding values in 20 normoalbuminuric Pima Indians with a similar duration of NIDDM. Over the ensuing 48 months the GFR (-34%) and filtration fraction (-13%) in the nephropathic patients declined further. The sieving coefficients of large, nearly impermeant dextrans (> 56 Angstrom radius) increased selectively and fractional clearances of albumin and IgG increased correspondingly by > 10-fold. Analysis of the findings with pore theory revealed: (1) a progressive decline in pore density and the ultrafiltration coefficient (K-f); and (2) broadening of glomerular pore-size distribution that resulted in greater prominence of large pores (> 70 Angstrom radius). We conclude that increasing loss of intrinsic ultrafiltration capacity is the predominant cause of the early and progressive decline in GFR that follows the development of nephropathy in NIDDM. We speculate that progressive impairment of barrier size-selectivity contributes to but does not fully account for the increasingly heavy proteinuria that is observed early in the course of this disorder.
C1 CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ.
   CLEVELAND CLIN FDN,CLEVELAND,OH.
   NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ.
   EMORY UNIV,SCH MED,DIV RENAL,ATLANTA,GA 30322.
RI Nelson, Robert/B-1470-2012
FU NIDDK NIH HHS [N01-DK-6-2285, N01-DK-7-2291]
NR 54
TC 53
Z9 54
U1 0
U2 0
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 JUN
PY 1995
VL 47
IS 6
BP 1781
EP 1789
DI 10.1038/ki.1995.246
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA QZ868
UT WOS:A1995QZ86800036
PM 7543961
ER

PT J
AU HE, CJ
   YANG, CW
   PETEN, EP
   LIU, ZH
   PATEL, A
   STRIKER, LJ
   STRIKER, GE
AF HE, CJ
   YANG, CW
   PETEN, EP
   LIU, ZH
   PATEL, A
   STRIKER, LJ
   STRIKER, GE
TI COLLAGEN AND COLLAGENASE MESSENGER-RNAS IN NORMAL AND SCLEROTIC
   GLOMERULI - PREDICTORS OF PROGRESSION AND RESPONSE TO THERAPY
SO KIDNEY INTERNATIONAL
LA English
DT Article
ID GROWTH-HORMONE; MESSENGER-RNA; DIABETES-MELLITUS; GLOMERULOSCLEROSIS;
   MICE; MOUSE; CELL
AB Progressive glomerulosclerosis is associated with decreasing kidney function, eventuating in end-stage renal failure. There are multiple components of the extracellular matrix, and the exact composition in various renal diseases is not known. Thus, we examined some of the major components of the extracellular matrix (ECM) in murine and human glomerular diseases. We studied matrix synthesis and degradation at the level of gene expression and ECM composition in the intact glomerulus. To determine whether the composition of sclerosis was similar among diseases, we examined a normal mouse strain and compared it with strains which spontaneously developed glomerulosclerosis. The baseline levels of matrix components varied between different mouse strains, and this level correlated with their propensity to develop glomerulosclerosis. In addition, when glomerulosclerosis was induced, the baseline ECM mRNA level predicted the subsequent outcome. We studied mice transgenic for bovine growth hormone, since they develop progressive glomerulosclerosis. Treatment with heparin substantially decreased the lesions without changes in type IV collagen mRNAs. However, there was an up-regulation of both the mRNA and enzyme activity for the 92 kD matrix metalloproteinase. In contrast, when these mice were treated with either angiotensin converting enzyme inhibitors or angiotensin II (Ang II) receptor antagonists, the glomerulosclerosis was accentuated histologically and the ECM synthetic and degradative mRNAs were elevated. These data suggest that the mRNA levels reflect response to therapy. We examined glomeruli from human nephrectomy specimens and found an increase in the mRNA levels for both the synthetic and degradative components of the ECM in those specimens with glomerulosclerosis. Preliminary examination of glomeruli isolated from renal biopsies reveals homogeneity in the alpha 2/alpha 3IV ratio among diabetics, but not among those with IgA nephropathy. These data suggest that modifications in ECM gene regulation may serve as predictors of progression.
C1 NIDDK,RENAL CELL BIOL SECT,METAB DIS BRANCH,BETHESDA,MD 20892.
NR 13
TC 10
Z9 10
U1 0
U2 0
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 JUN
PY 1995
VL 47
SU 49
BP S39
EP S43
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA RC598
UT WOS:A1995RC59800010
PM 7674591
ER

PT J
AU YANG, CW
   VLASSARA, H
   STRIKER, GE
   STRIKER, LJ
AF YANG, CW
   VLASSARA, H
   STRIKER, GE
   STRIKER, LJ
TI ADMINISTRATION OF AGES IN-VIVO INDUCES GENES IMPLICATED IN DIABETIC
   GLOMERULOSCLEROSIS
SO KIDNEY INTERNATIONAL
LA English
DT Article
ID GLYCOSYLATION END-PRODUCTS; EXTRACELLULAR-MATRIX; MODIFIED PROTEINS;
   MESANGIAL CELLS; TRANSGENIC MICE; MESSENGER-RNA; GROWTH-FACTOR;
   AMINOGUANIDINE; NEPHROPATHY; TISSUE
AB Administration of advanced glycosylation end products (AGEs), prepared on mouse albumin, to normal young adult mice, resulted in an increase in mean glomerular volume and up-regulation of laminin B1 and alpha 1 type IV collagen mRNAs measured by competitive PCR in single microdissected glomeruli. Both glomerular hypertrophy and overexpression of genes coding for extracellular matrix were abrogated when aminoguanidine, an inhibitor of AGE cross-linking, was added to the AGEs injections, suggesting that the glomerular response to AGEs was specific. The effects of AGEs administration in vivo are comparable to those occuring in the early stage of diabetic nephropathy, suggesting a participation of AGEs in these events.
C1 NIDDK,BETHESDA,MD 20892.
NR 24
TC 8
Z9 8
U1 0
U2 0
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 JUN
PY 1995
VL 47
SU 49
BP S55
EP S58
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA RC598
UT WOS:A1995RC59800014
ER

PT J
AU BERNSTEIN, EF
   FISHER, LW
   LI, KH
   LEBARON, RG
   TAN, EML
   UITTO, J
AF BERNSTEIN, EF
   FISHER, LW
   LI, KH
   LEBARON, RG
   TAN, EML
   UITTO, J
TI DIFFERENTIAL EXPRESSION OF THE VERSICAN AND DECORIN GENES IN PHOTOAGED
   AND SUN-PROTECTED SKIN - COMPARISON BY IMMUNOHISTOCHEMICAL AND NORTHERN
   ANALYSES
SO LABORATORY INVESTIGATION
LA English
DT Article
DE CUTANEOUS AGING; SOLAR ELASTOSIS; ULTRAVIOLET LIGHT
ID MESSENGER-RNA LEVELS; SMALL PROTEOGLYCAN-I; GROWTH FACTOR-BETA;
   FIBROBLAST PROTEOGLYCAN; ULTRAVIOLET-RADIATION; EXTRACELLULAR-MATRIX;
   DERMAL FIBROBLASTS; COLLAGEN FORMATION; ELASTIC FIBERS; DAMAGED SKIN
AB BACKGROUND: Chronic sun exposure induces numerous changes in exposed skin; the most striking histopathologic change is the massive accumulation of material with the staining characteristics of elastin, termed solar elastosis, in the superficial dermis. Previous studies have identified elastic fibers within areas of solar elastosis, as well as a decrease in collagen content. Recently, the large chondroitin sulfate (CS) proteoglycan, versican, has been identified in the dermis in association with elastic fibers, and the smaller CS proteoglycan, decorin, has been shown to codistribute with collagen fibers. Thus, changes in expression of these CS proteoglycans might be expected in photoaging and may help to explain the clinical alterations of chronically sun-exposed skin.
   EXPERIMENTAL LESION: Immunohistochemical staining and confocal laser scanning microscopy for versican and decorin was performed on paired tissue samples from photoaged and non-sun-exposed skin taken from the same individuals. To investigate versican and decorin mRNA expression, Northern analysis was performed on paired fibroblast cultures derived from tissue explants of photoaged and non-sun-exposed skin.
   RESULTS: Immunohistochemical staining and confocal laser scanning microscopy revealed a massive accumulation of versican localized to the abnormally large fibers comprising solar elastosis in the superficial and mid-dermis of photoaged specimens. Decorin staining was greatly decreased within the area of solar elastosis. Similarly, changes in mRNA were measured from fibroblast cultures, with a significant increase in versican mRNA in cultures derived from photoaged skin, whereas decorin mRNA levels were significantly decreased in photoaged skin.
   CONCLUSIONS: This study provides further evidence for the close association of versican with elastic fibers and decorin with collagen fibers, even in the situation of abnormal fiber deposition occurring in photodamaged skin. In addition, changes in versican and decorin immunostaining are accompanied by similar alterations in gene expression.
C1 JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA.
   JEFFERSON MED COLL,DEPT PATHOL & CELL BIOL,PHILADELPHIA,PA.
   THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107.
   NIDR,BONE RES BRANCH,BETHESDA,MD 20892.
   DEPT CELL BIOL,LA JOLLA,CA.
RP BERNSTEIN, EF (reprint author), JEFFERSON MED COLL,DEPT DERMATOL,233 S 10TH ST,ROOM 450,BLUEMLE LIFE SCI BLDG,PHILADELPHIA,PA 19107, USA.
RI LeBaron, Richard/K-4722-2013
OI LeBaron, Richard/0000-0002-7770-305X
FU NIAMS NIH HHS [R01-AR28450, T32-AR7561]
NR 45
TC 77
Z9 78
U1 0
U2 5
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD JUN
PY 1995
VL 72
IS 6
BP 662
EP 669
PG 8
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA RD422
UT WOS:A1995RD42200006
PM 7783424
ER

PT J
AU TAKEYA, M
   YAMASHIRO, S
   YOSHIMURA, T
   TAKAHASHI, K
AF TAKEYA, M
   YAMASHIRO, S
   YOSHIMURA, T
   TAKAHASHI, K
TI IMMUNOPHENOTYPIC AND IMMUNOELECTRON MICROSCOPIC CHARACTERIZATION OF
   MAJOR CONSTITUENT CELLS IN MALIGNANT FIBROUS HISTIOCYTOMA USING HUMAN
   CELL-LINES AND THEIR TRANSPLANTED TUMORS IN IMMUNODEFICIENT MICE
SO LABORATORY INVESTIGATION
LA English
DT Article
DE MONOCYTE CHEMOATTRACTANT PROTEIN-1; NORTHERN BLOT HYBRIDIZATION
ID COLONY-STIMULATING FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1;
   SOFT-TISSUE TUMORS; MONOCLONAL-ANTIBODY; MACROPHAGE; DIFFERENTIATION;
   ORIGIN; PROLIFERATION; EXPRESSION; ANTIGENS
AB BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life. Its histogenesis, however, is still a matter of debate because of its various cellular components.
   EXPERIMENTAL DESIGN: To elucidate the nature of tumor cells of MFH, six human MFH cell lines were compared immunohistochemically and immunoelectron microscopically with fibrosarcoma and fibroblast cell lines. lit vitro differentiation of tumor cells was evaluated after the treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, macrophage CSF, and granulocyte-macrophage CSF. Heterotransplantation of MFH tumor cells into nude mice and severe combined immunodeficient mice was performed to examine whether the tumor cells differentiate toward histiocytes or not. Gene expression of monocyte chemoattractant protein-1 in cultured tumor cells and transplanted tumors was also evaluated.
   RESULTS: All MFH cell lines examined were positive for collagen type I and prolyl hydroxylase. They failed to react with most anti-myeloid mAb such as CD11c, CD14, CD15, CD33, CD35, CD45, anti-HLA-DR, and PM-2K. Several Ab, including CD13, CD32, CD68, CD71, and HAM56, were reactive with MFH cells. However, all of these Ab were also reactive with fibrosarcoma and/or fibroblastic cell. lines. These data indicate that MFH cell lines possess immunophenotypic characteristics very similar to those of fibrosarcoma and fibroblastic cell lines. In vitro treatment of tumor cells with TPA, IL-3, macrophage CSF, granulocyte-macrophage CSF, or their combination did not change their immunophenotypic characteristics and did not induce differentiation toward histiocytes (macrophages). Transplantation of tumor cells into nude mice and severe combined immunodeficient mice produced tumors similar in histology to human MFH. Tumor cells in the transplanted tumors revealed the same immunophenotypic characterization that they did in vitro. No in vivo differentiation of tumor cells toward histiocytes was observed. Immunohistochemical staining with anti-mouse macrophage mAb revealed marked infiltration of macrophages of mouse origin. Quantitative immunoelectron microscopy disclosed that these cells coincided with histiocyte-like cells. Gene expression of monocyte chemoattractant protein-1 was detected in all MFH cell lines as well as in transplanted tumors.
   CONCLUSIONS: The histiocyte-like cells in malignant fibrous histiocytoma are not a neoplastic component but rather infiltrated macrophages attracted by tumor-derived monocyte chemoattractant(s), and the tumor cells belong to a fibroblastic lineage differentiated from mesenchymal cells.
C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701.
RP TAKEYA, M (reprint author), KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,2-2-1 HONJO,KUMAMOTO 860,JAPAN.
NR 45
TC 31
Z9 32
U1 0
U2 1
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD JUN
PY 1995
VL 72
IS 6
BP 679
EP 688
PG 10
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA RD422
UT WOS:A1995RD42200008
PM 7783426
ER

PT J
AU LAPIS, K
   SAROSI, I
   BOCSI, J
   THORGEIRSSON, UP
AF LAPIS, K
   SAROSI, I
   BOCSI, J
   THORGEIRSSON, UP
TI CYTOKERATIN PATTERNS OF LIVER CARCINOMAS INDUCED BY DIETHYLNITROSAMINE
   IN MONKEYS
SO LABORATORY INVESTIGATION
LA English
DT Article
DE HEPATOCELLULAR CARCINOMAS; DEN-INDUCED LIVER CANCER;
   HEPATOCARCINOGENESIS IN MONKEYS; DEN-INDUCED HEPATOCARCINOGENESIS;
   IMMUNOCYTOCHEMISTRY IN LIVER CANCER; LUNG METASTASIS OF LIVER CANCER
ID INTERMEDIATE FILAMENT PROTEINS; HEPATOCELLULAR-CARCINOMA;
   MONOCLONAL-ANTIBODIES; OVAL CELLS; DIFFERENTIAL-DIAGNOSIS; RAT-LIVER;
   DUCTULAR PROLIFERATION; KERATIN POLYPEPTIDES; BILE-DUCTS; STEM-CELL
AB BACKGROUND: Although the general conception is that hepatocyte- and bile duct-specific cytokeratin (CK) patterns are maintained throughout the neoplastic process, there is an increasing number of reports showing deviation from the rule. CK patterns have been found to be similar across species barriers, so it could be expected that studying the CK patterns of experimentally induced liver tumors may contribute to the elucidation of these controversies.
   EXPERIMENTAL DESIGN: A CK immunohistochemical study was carried out on histologic sections from hepatocellular carcinomas (HCCs) and preneoplastic lesions from 118 monkeys chronically dosed with diethylnitrosamine (DEN), using mAbs to CK 8, CK 18, CR 7, and CK 19.
   RESULTS: Normal monkey hepatocytes differed from human hepatocytes by displaying CK 19 in addition to the CK 8/CK 18 pairs, whereas the CK pattern of bile duct epithelial cells was identical in monkey and human liver. In association with DEN-induced hepatocarcinogenesis, heterogeneity was observed in the CK expression, both in the HCCs and nontumorous parts of the livers. The majority of the HCC cases displayed one of the three CKs normally present in monkey hepatocytes, whereas positive expression of all three CKs (CK 8, CK 18, CK 19) and negative CK 7 was preserved in only 19.5% of the HCC cases. A so-called mixed staining pattern (negative and positive CK staining within the same tumor) was observed in approximately one-fourth of the cases. There was no correlation between the preservation of the hepatocyte-specific CK pattern and the degree of differentiation, tumor grade, or DNA ploidy of the HCCs. In approximately 10% of the primary tumors, CK 7 was expressed in the entire parenchymal cell compartment of the HCC nodules, whereas it was present in a mixed staining pattern in more than half of the cases. In lung metastases, CK 7 was less common, only expressed in approximately one-fourth of the cases. Alterations in the CK patterns were observed in the nonneoplastic hepatocytes of the tumor-bearing monkeys. These included mixed staining patterns in which the CKs appeared as positive and negative regenerating nodules side-by-side. As was observed in the HCCs, CK 7 was more commonly expressed in the nonneoplastic parenchyma in the form of mixed staining pattern than the other three CKs. Moreover, CK 7-negative HCCs occurred more frequently in CK 7-negative livers than in positive livers. Proliferation of CK 7- and CK 19-positive bile ductules and bile ductular-like (oval) cells was frequently associated with the DEN-induced liver injury and hepatocarcinogenesis.
   CONCLUSIONS: This is the first report on CK expression in monkey liver. The findings show that the hepatocyte specific pattern is not always preserved during DEN-induced hepatocarcinogenesis and may therefore not be useful in differentiating between HCCs and cholangiocarcinomas.
C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892.
RP LAPIS, K (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPTL CANC RES 1,ULLOI UT 26,H-1085 BUDAPEST,HUNGARY.
NR 73
TC 7
Z9 7
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD JUN
PY 1995
VL 72
IS 6
BP 748
EP 759
PG 12
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA RD422
UT WOS:A1995RD42200016
PM 7540236
ER

PT J
AU DUBREZ, L
   GOLDWASSER, F
   GENNE, P
   POMMIER, Y
   SOLARY, E
AF DUBREZ, L
   GOLDWASSER, F
   GENNE, P
   POMMIER, Y
   SOLARY, E
TI THE ROLE OF CELL-CYCLE REGULATION AND APOPTOSIS TRIGGERING IN
   DETERMINING THE SENSITIVITY OF LEUKEMIC-CELLS TO TOPOISOMERASE-I AND
   TOPOISOMERASE-II INHIBITORS
SO LEUKEMIA
LA English
DT Article
DE TOPOISOMERASE; APOPTOSIS; CELL CYCLE; LEUKEMIC CELLS; DRUG RESISTANCE
ID ACUTE MYELOGENOUS LEUKEMIA; DNA STRAND BREAKS; MULTIDRUG-RESISTANCE;
   HL-60 CELLS; CYTO-TOXICITY; DIFFERENTIAL INDUCTION; CATALYTIC ACTIVITY;
   P-GLYCOPROTEIN; MESSENGER-RNA; C-MYC
AB Topoisomerase (topo) inhibitors induce enzyme-linked DNA breaks. Resulting DNA damage can lead to cell cycle arrest and/or cell death by apoptosis. The sensitivity of five human leukemic cell lines to topo I (camptothecin or CPT) and topo II (etoposide or VP-16) inhibitors varied widely (100-fold for CPT and 30-fold for VP-16). Three cell lines were more sensitive (BV173, HL60, U937) and two cell lines were resistant (K562, KCL22) to both drugs. None of these cell lines were selected for drug resistance and overexpressed mdr1 gene. Their sensitivity was not related to their doubling time nor to cell cycle repartition. The initial DNA damage (cleavable complexes) induced by topo I and II inhibitors was measured as DNA-protein crosslinks (DPC) using alkaline elution. Neither DPC level induced by 30-min treatment with CPT or VP-16 nor the levels of topo 1, topo II alpha and topo II beta mRNA were related to sensitivity. Electron microscopy and DNA fragmentation measured by filter elution and agarose gel electrophoresis demonstrated that apoptosis was induced by both drugs in the five cell lines. The kinetics of DNA fragmentation was related to cell sensitivity. At drug concentrations higher than IC50, DNA fragmentation increased very rapidly in the three sensitive, compared with the two resistant, cell lines. Continuous exposure to both drugs induced cell cycle arrest in either G2 or S phase that was related both to cell sensitivity and drug concentration. Comparison between cell lines indicated that the ability of cells to arrest cell cycle in G2 or S phase was related to their drug sensitivity and increased with cell resistance. In a given cell line, cell cycle progression was observed to be progressively inhibited by increasing drug concentrations. Treatment of synchronized cells demonstrated that highly cytotoxic drug concentration induced a complete inhibition of cell cycle progression. Altogether, these data suggest that the ability of leukemic cell lines to regulate cell cycle progression and to trigger apoptosis is more indicative of their sensitivity to topoisomerase poisons than cleavable complexes induced by these drugs.
C1 FAC MED DIJON,ONCOHEMATOL & PHARMACOL LAB,F-21033 DIJON,FRANCE.
   NATL CANC INST,MOLEC PHARMACOL LAB,BETHESDA,MD.
RI Dubrez, Laurence/I-4971-2016
OI Dubrez, Laurence/0000-0002-7030-2181
NR 67
TC 124
Z9 126
U1 1
U2 3
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 1995
VL 9
IS 6
BP 1013
EP 1024
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA RH786
UT WOS:A1995RH78600015
PM 7596166
ER

PT J
AU JOHNSON, BE
   KELLEY, MJ
AF JOHNSON, BE
   KELLEY, MJ
TI BIOLOGY OF SMALL-CELL LUNG-CANCER
SO LUNG CANCER
LA English
DT Article; Proceedings Paper
CT Educational Symposium on Current Perspectives in the Treatment of Small
   Cell Lung Cancer, at the VII World Congress on Lung Cancer
CY JUN   26, 1994
CL COLORADO SPRINGS, CO
DE SMALL CELL LUNG CANCER, BIOLOGY; LUNG CANCER, GENE ABNORMALITIES; LUNG
   CANCER, GROWTH FACTOR PRODUCTION
ID GASTRIN-RELEASING PEPTIDE; RETINOBLASTOMA SUSCEPTIBILITY GENE; BRONCHIAL
   EPITHELIAL-CELLS; CHROMOSOMAL REGION 3P21; TUMOR-SUPPRESSOR GENE;
   HOMOZYGOUS DELETION; CARCINOMA CELLS; NEUROMEDIN-B; SHORT ARM; RB GENE
AB The bombesin-like peptides can function as autocrine growth factors in lung cancer and candidate tumor suppressor genes on chromosomes 3 and 9 play important roles in lung cancer. Bombesin-like peptides can function as mitogens for normal bronchial epithelial cells and lung cancer cell lines. The monoclonal antibody directed against gastrin releasing peptide and bombesin, 2All, can inhibit the growth of small cell lung cancer in vitro and in vivo and intravenous administration has induced a clinical remission in a patient with relapsed small cell lung cancer. The loss of a portion of one of the two short arms of chromosome 3 (3p) is identified in nearly 100% of tumor cell lines and tumors from patients with small cell lung cancer. Introduction of chromosome 3 into tumor cell lines suppresses their tumorigenicity in athymic nude mice, one of the characteristics of the cancer phenotype. Both copies of the candidate tumor suppressor gene on chromosome 9, CDKN2, are deleted in approximately one-fourth of lung cancer cell lines examined and the protein product of CDKN2 p16 is undetectable in one-third of the lung cancer cell lines studied. The CDKN2 gene is inactivated more commonly in non-small cell lung cancer than small cell lung cancer while the retinoblastoma gene is inactivated more commonly in small cell lung cancer than non-small cell lung cancer. It appears that a single defect in this cell cycle pathway is necessary for unregulated growth in lung cancer and current evidence suggests these defects differ between small cell and non-small cell lung cancer.
RP JOHNSON, BE (reprint author), NATL NAVAL MED CTR, NCI,NAVY MED ONCOL BRANCH,LUNG CANC BIOL SECT, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA.
NR 88
TC 7
Z9 7
U1 0
U2 16
PU ELSEVIER SCI PUBL IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0169-5002
J9 LUNG CANCER-J IASLC
JI Lung Cancer
PD JUN
PY 1995
VL 12
SU 3
BP S5
EP S16
DI 10.1016/S0169-5002(10)80014-5
PG 12
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA RL745
UT WOS:A1995RL74500002
PM 7551956
ER

PT J
AU SUMMERS, RM
   HEDLUND, LW
   COFER, GP
   GOTTSMAN, MB
   MANIBO, JF
   JOHNSON, GA
AF SUMMERS, RM
   HEDLUND, LW
   COFER, GP
   GOTTSMAN, MB
   MANIBO, JF
   JOHNSON, GA
TI MR MICROSCOPY OF THE RAT CAROTID-ARTERY AFTER BALLOON INJURY BY USING AN
   IMPLANTED IMAGING COIL
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE IN VIVO MR MICROSCOPY; IMPLANTED RF COILS; CAROTID ARTERY; ANGIOPLASTY
ID PROLIFERATION; NMR
AB Neointimal hyperplasia after angioplasty was followed in vivo in rats by using MR microscopy and surgically implanted RF imaging coils. By using an inductively coupled pick-up coil, the arteries were imaged 4 days before and 3, 7, and 14 days after angioplasty with a 3DFT spin echo sequence. Eight of 10 angioplastied rats showed moderate to severe stensois based MR measures of lumen diameter reduction from baseline images, There was a good correlation between total wall thickness between MR and hematoxylin and eosin (HandE)-stained sections obtained on the fast day. Arteries in the intact and sham groups remained unchanged from baseline measurements. Because this imaging technique examines the artery under in vivo conditions of arterial pressure and flow, it promises to be a useful tool far evaluating pharmacological and mechanical methods of reducing the incidence of vascular stenosis.
C1 DUKE UNIV,MED CTR,DUMC 3302,CTR INVIVO MICROSCOPY,DURHAM,NC 27710.
   NIH,DEPT RADIOL,BETHESDA,MD.
OI Hedlund, Laurence/0000-0001-5275-0397; Johnson,
   G.Allan/0000-0002-7606-5447
FU PHS HHS [P41 05959-04]
NR 12
TC 29
Z9 30
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0740-3194
J9 MAGNET RESON MED
JI Magn.Reson.Med.
PD JUN
PY 1995
VL 33
IS 6
BP 785
EP 789
DI 10.1002/mrm.1910330607
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA RA064
UT WOS:A1995RA06400006
PM 7651114
ER

PT J
AU BIESECKER, LG
   LAXOVA, R
AF BIESECKER, LG
   LAXOVA, R
TI MANAGEMENT OF FETAL HYDRONEPHROSIS
SO MAYO CLINIC PROCEEDINGS
LA English
DT Letter
C1 UNIV WISCONSIN HOSP,MADISON,WI.
RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU MAYO CLINIC PROCEEDINGS
PI ROCHESTER
PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905
SN 0025-6196
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD JUN
PY 1995
VL 70
IS 6
BP 603
EP 603
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA RB091
UT WOS:A1995RB09100020
PM 7776727
ER

PT J
AU GOORIN, A
   STROTHER, D
   POPLACK, D
   LETVAK, LA
   GEORGE, M
   LINK, M
AF GOORIN, A
   STROTHER, D
   POPLACK, D
   LETVAK, LA
   GEORGE, M
   LINK, M
TI SAFETY AND EFFICACY OF L-LEUCOVORIN RESCUE FOLLOWING HIGH-DOSE
   METHOTREXATE FOR OSTEOSARCOMA
SO MEDICAL AND PEDIATRIC ONCOLOGY
LA English
DT Article
DE OSTEOSARCOMA; L-LEUCOVORIN RESCUE; D, L-LEUCOVORIN; METHOTREXATE
ID ADJUVANT CHEMOTHERAPY; OSTEO-SARCOMA; CITROVORUM-FACTOR;
   5-FORMYLTETRAHYDROFOLATE; TRIAL
AB High-dose methotrexate with leucovorin rescue (HDMTX-LCV) is an important component of regimens used in the treatment of osteosarcoma. As of this writing the commercially available form of leucovorin is a racemic mixture of d- and l-diastereoisomers; the l-isomer is the active component. This study describes the efficacy and safety of l-leucovorin in HDMTX-LCV regimens. Fifteen patients with osteosarcoma who were enrolled into or treated according to Pediatric Oncology Group protocols 8759 and 8651 received l-leucovorin (7.5 mg every 6 hours) in place of d,l-leucovorin following high-dose methotrexate. Safely data were collected for 1 week after each course until any toxicities resolved. The mean number of l-leucovorin doses per course was 16.2 and the mean total dose per course was 126 mg. Adverse experiences were generally mild or moderate and occurred in 54 (60%) of 90 courses of l-leucovorin therapy. One l-leucovorin patient, who had inadequate methotrexate rescue, developed severe typhlitis. There were no instances of severe, acute methotrexate toxicity. Myelosuppression was seen but, in general, was not severe. These results support the conclusion that l-leucovorin effectively rescues patients from the toxicity of high-dose methotrexate. (C) 1995 Wiley-Liss, Inc.
C1 MED COLL WISCONSIN,MILWAUKEE,WI 53226.
   HARVARD UNIV,SCH MED,BOSTON,MA.
   NCI,BETHESDA,MD 20892.
   STANFORD UNIV,SCH MED,STANFORD,CA 94305.
   AMER CYANAMID CO,LEDERLE LABS,CLIN DEV,PEARL RIVER,NY 10965.
NR 26
TC 12
Z9 12
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 0098-1532
J9 MED PEDIATR ONCOL
JI Med. Pediatr. Oncol.
PD JUN
PY 1995
VL 24
IS 6
BP 362
EP 367
DI 10.1002/mpo.2950240605
PG 6
WC Oncology; Pediatrics
SC Oncology; Pediatrics
GA QZ329
UT WOS:A1995QZ32900004
PM 7715542
ER

PT J
AU ORY, MG
AF ORY, MG
TI AGING, HEALTH, AND CULTURE - THE CONTRIBUTION OF MEDICAL ANTHROPOLOGY
SO MEDICAL ANTHROPOLOGY QUARTERLY
LA English
DT Note
RP ORY, MG (reprint author), NIA,BSR,GATEWAY BLDG,SUITE 533,7201 WISCONSIN AVE,MSC 920,BETHESDA,MD 20814, USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER ANTHROPOLOGICAL ASSOC
PI ARLINGTON
PA 4350 NORTH FAIRFAX DRIVE SUITE 640, ARLINGTON, VA 22203
SN 0745-5194
J9 MED ANTHROPOL Q
JI Med. Anthropol. Q.
PD JUN
PY 1995
VL 9
IS 2
BP 281
EP 283
DI 10.1525/maq.1995.9.2.02a00100
PG 3
WC Anthropology; Public, Environmental & Occupational Health; Social
   Sciences, Biomedical
SC Anthropology; Public, Environmental & Occupational Health; Biomedical
   Social Sciences
GA RC487
UT WOS:A1995RC48700010
PM 7671119
ER

PT J
AU SWINBURN, BA
   GIANCHANDANI, R
   SAAD, MF
   LILLIOJA, S
AF SWINBURN, BA
   GIANCHANDANI, R
   SAAD, MF
   LILLIOJA, S
TI IN-VIVO BETA-CELL FUNCTION AT THE TRANSITION TO EARLY
   NON-INSULIN-DEPENDENT DIABETES-MELLITUS
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; PIMA-INDIANS; SECRETORY CAPACITY;
   RESISTANCE; RELEASE; INVIVO; HYPERGLYCEMIA; MECHANISM; DISPOSAL; OBESITY
AB Impaired insulin secretion occurs at some stage in the development of non-insulin dependent diabetes mellitus (NIDDM), possibly during impaired glucose tolerance (IGT) or early NIDDM. To assess insulin secretion at these critical stages, we measured the first-phase insulin response (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal glucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7.8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and insulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although as a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired insulin secretion. The first-phase response to glucose was markedly reduced in absolute terms (P < .001), but all secretion indices were impaired relative to the degree of insulin resistance (P = .05 to P < .0001). These results suggest that in Pima Indians, impairment of insulin secretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, seems intact, although a subtle defect in the first-phase insulin response to glucose could not be ruled out in this study. Glucose sensing for first-phase secretion may be one of the early secretory defects in the progression of glucose intolerance and seems to be critical at the transition from IGT to early NIDDM. Copyright (C) 1995 by W.B. Saunders Company
C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016.
RI Lillioja, Stephen/A-8185-2012; 
OI Lillioja, Stephen/0000-0001-5333-5240
NR 44
TC 16
Z9 20
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 1995
VL 44
IS 6
BP 757
EP 764
DI 10.1016/0026-0495(95)90189-2
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA RB863
UT WOS:A1995RB86300013
PM 7783660
ER

PT J
AU SANDERSON, KE
   HESSEL, A
   RUDD, KE
AF SANDERSON, KE
   HESSEL, A
   RUDD, KE
TI GENETIC-MAP OF SALMONELLA-TYPHIMURIUM, EDITION-VIII
SO MICROBIOLOGICAL REVIEWS
LA English
DT Review
ID ESCHERICHIA-COLI K-12; OUTER-MEMBRANE PROTEIN; AMINO-ACID-SEQUENCE;
   FLAGELLAR BASAL BODY; BACTERIAL PHOSPHOTRANSFERASE SYSTEM; ALKYL
   HYDROPEROXIDE REDUCTASE; ALTERNATIVE SIGMA-FACTOR; DNA POLYMERASE-III;
   MONONUCLEOTIDE TRANSPORT-SYSTEM; RESTRICTION-MODIFICATION SYSTEM
AB We present edition VIII of the genetic map of Salmonella typhimurium LT2. We list a total of 1,159 genes, 1,080 of which have been located on the circular chromosome and 29 of which are on pSLT, the 90-kb plasmid usually found in LT2 lines. The remaining 50 genes are not yet mapped. The coordinate system used in this edition is neither minutes of transfer time in conjugation crosses nor units representing ''phage lengths'' of DNA of the transducing phage P22, as used in earlier editions, but centisomes and kilobases based on physical analysis of the lengths of DNA segments between genes. Some of these lengths have been determined by digestion of DNA by rare-cutting endonucleases and separation of fragments by pulsed-field gel electrophoresis. Other lengths have been determined by analysis of DNA sequences in GenBank. We have constructed StySeq1, which incorporates all Salmonella DNA sequence data known to us. StySeq1 comprises over 548 kb of nonredundant chromosomal genomic sequences, representing 11.4% of the chromosome which is estimated to be just over 4,800 kb in length. Most of these sequences were assigned locations on the chromosome, in some cases by analogy with mapped Escherichia coli sequences.
C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894.
RP SANDERSON, KE (reprint author), UNIV CALGARY,DEPT BIOL SCI,CTR SALMONELLA GENET STOCK,2500 UNIV DR 1 NW,CALGARY,AB T2N 1N4,CANADA.
FU NIAID NIH HHS [R01 AI34829]
NR 773
TC 108
Z9 108
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171
SN 0146-0749
J9 MICROBIOL REV
JI Microbiol. Rev.
PD JUN
PY 1995
VL 59
IS 2
BP 241
EP 303
PG 63
WC Microbiology
SC Microbiology
GA RB443
UT WOS:A1995RB44300004
PM 7603411
ER

PT J
AU VUGMAN, I
   HAND, AR
AF VUGMAN, I
   HAND, AR
TI QUANTITATIVE IMMUNOCYTOCHEMICAL STUDY OF SECRETORY PROTEIN EXPRESSION IN
   PAROTID-GLANDS OF RATS CHRONICALLY TREATED WITH ISOPROTERENOL
SO MICROSCOPY RESEARCH AND TECHNIQUE
LA English
DT Article
DE ACINAR CELLS; DUCT CELLS; DIFFERENTIATION; IMMUNOGOLD; AMYLASE;
   PROLINE-RICH PROTEINS
ID PROLINE-RICH PROTEIN; PANCREATIC ACINAR-CELLS; DUCT CELLS;
   SUBMANDIBULAR-GLAND; SALIVARY PROTEINS; REGULATORY SUBUNITS; MULTIGENE
   FAMILIES; MESSENGER-RNAS; DIABETIC RATS; LIQUID DIET
AB Chronic treatment of mice and rats with isoproterenol (IPR) causes marked hypertrophy and hyperplasia of the salivary glands, and alters the expression of several secretory proteins. We used quantitative postembedding immunogold labeling to study the cellular responses in the rat parotid gland during daily (up to 10 days) injections of IPR and during recovery (up to 14 days) after cessation of IPR treatment. Labeling densities of acinar cell secretory granules with antibodies to amylase and protein SMG-B1 (cross-reactive with the rat homologue of Parotid Secretory Protein, PSP) fell to 10% of control levels after 8-10 IPR injections, then increased during recovery, paralleling previous biochemical determinations of changes in protein and mRNA levels. With antibodies to proline-rich proteins (PRP), labeling densities initially fell, then subsequently showed considerable variability, but never exceeded control levels. These results contrast with biochemical determinations showing a marked induction of PRP synthesis, and may have both immunological and structural explanations.
   Occasional intercalated duct cells located close to the acini underwent differentiation toward an acinar-like phenotype as a result of IPR treatment. After 1-2 IPR injections, the secretory granules of these cells labeled with antibodies to amylase and PRP. Subsequently, the granules appeared electron-lucent and were increased in size and number. These observations support earlier work, suggesting that intercalated duct cells may differentiate into other gland cell types. (C) 1995 Wiley-Liss, Inc.
C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA.
NR 60
TC 25
Z9 27
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-910X
EI 1097-0029
J9 MICROSC RES TECHNIQ
JI Microsc. Res. Tech.
PD JUN 1
PY 1995
VL 31
IS 2
BP 106
EP 117
DI 10.1002/jemt.1070310203
PG 12
WC Anatomy & Morphology; Biology; Microscopy
SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics;
   Microscopy
GA QY953
UT WOS:A1995QY95300002
PM 7544654
ER

PT J
AU RISCO, C
   DASILVA, PP
AF RISCO, C
   DASILVA, PP
TI CELLULAR FUNCTIONS DURING ACTIVATION AND DAMAGE BY PATHOGENS -
   IMMUNOGOLD STUDIES OF THE INTERACTION OF BACTERIAL-ENDOTOXINS WITH
   TARGET-CELLS
SO MICROSCOPY RESEARCH AND TECHNIQUE
LA English
DT Review
DE IMMUNOCYTOCHEMISTRY; LIPOPOLYSACCHARIDE; PNEUMOCYTE; MACROPHAGE;
   MICROTUBULES
ID ESCHERICHIA-COLI LIPOPOLYSACCHARIDE; NECROSIS-FACTOR-ALPHA;
   GRAM-NEGATIVE SEPSIS; II CELLS; BINDING-PROTEIN; HUMAN-MONOCYTES; RAT
   LUNG; LIPID-A; SUBCELLULAR-DISTRIBUTION; PERITONEAL-MACROPHAGES
AB Bacterial endotoxins (lipopolysaccharides or LPS) are active components of Gram-negative bacteria that act on numerous cellular functions through the processes of cell activation and damage. The molecular mechanisms involved in the ''endotoxic phenomenon'' are not defined yet, although extensive studies have been carried out. Immunogold and electron microscopy (EM) have contributed to identify the primary target cells of endotoxins and the subcellular systems that receive the direct action of these bacterial agents. Here, we review our studies on immunogold detection of endotoxins in cellular and subcellular systems. The analysis of the interaction between endotoxins and cells was focussed on the following aspects: (1) morphological characteristics of the LPS aqueous suspensions used in experimental work; (2) binding of endotoxins to the plasma membrane of type II pneumocytes and alveolar macrophages (two of their cellular targets), and influence of the state of aggregation of the LPS; (3) movement and distribution of endotoxins inside the cell, from the plasma membrane to the nucleoplasm; and (4) interaction of LPS with microtubules and its effects on the integrity of the microtubular network. These approaches provide information at the molecular level as well as data for the establishment of physiological models of endotoxicity. (C) 1995 Wiley-Liss, Inc.*
C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
   NCI,MATH BIOL LAB,STRUCT BIOL SECT,FREDERICK,MD 21702.
NR 116
TC 23
Z9 24
U1 0
U2 3
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 1059-910X
J9 MICROSC RES TECHNIQ
JI Microsc. Res. Tech.
PD JUN 1
PY 1995
VL 31
IS 2
BP 141
EP 158
DI 10.1002/jemt.1070310206
PG 18
WC Anatomy & Morphology; Biology; Microscopy
SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics;
   Microscopy
GA QY953
UT WOS:A1995QY95300005
PM 7655088
ER

PT J
AU RULONG, S
   ZHOU, RP
   TSARFATY, I
   HUGHES, S
   VANDEWOUDE, G
   DASILVA, PP
AF RULONG, S
   ZHOU, RP
   TSARFATY, I
   HUGHES, S
   VANDEWOUDE, G
   DASILVA, PP
TI IMMUNOGOLD LABELING OF ONCOGENIC AND TUMOR-RELATED PROTEINS
SO MICROSCOPY RESEARCH AND TECHNIQUE
LA English
DT Article
DE IMMUNOGOLD; ELECTRON MICROSCOPY (EM); ONCOGENE; MOS; MET; SKI; MUD;
   MUCIN; IMMUNOCYTOCHEMISTRY
ID HEPATOCYTE GROWTH-FACTOR; MOLONEY SARCOMA-VIRUS; C-SKI ONCOGENE;
   XENOPUS-OOCYTES; SCATTER FACTOR; MET PROTOONCOGENE; MAP KINASE;
   SUBCELLULAR-LOCALIZATION; MEIOTIC MATURATION; PLASMA-MEMBRANE
AB Immunogold labeling electron microscopy technique has been used to study the ultrastructural localization of oncogenic proteins: Mos, Met, Ski, and the tumor-associated protein, Muc1, as well as their relationship with other tumor-related proteins. By pre- and postembedding immunogold labeling electron microscopy techniques, we showed that the Mos protein pp39(mos) colocalized with microtubule bundles, suggesting that microtubulin or microtubule-associated protein(s) may be the substrate of Mos. Met protein was labeled at the microvilli of the lumen that are formed in cultured T47D cells, implying its potential involvement in lumen formation. Ski localization experiments revealed a unique globular structure ''Ski body'' that is present inside the nucleus of interphase chicken embryo fibroblast infected with Ski cDNA FB29 and FB2-29. Ski bodies were also found scattered in the cytoplasm of metaphase FB29 and FB2-29 Ski expressing chicken embryo fibroblasts. In T47D cells, tumor-associated protein Muc1 was associated with both the plasma membrane and the membranes of secretory vesicles in the cytoplasm. In MUC1 infected NIH3T3 cells, however, labeling showed that in addition to the plasma membrane and the membranes of secretory vesicles, some Mud gold spheres were seen inside the secretory vesicles, suggesting that the subcellular localization of the protein may vary in different cell types. (C) 1995 Wiley-Liss, Inc.
C1 NCI,FREDERICK CANC RES & DEV CTR,STUCT BIOL SECT,DCBDC INTRAMURAL RES PROGRAM,FREDERICK,MD 21702.
RP RULONG, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BLDG 538,RM 124,FREDERICK,MD 21702, USA.
NR 90
TC 4
Z9 4
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 1059-910X
J9 MICROSC RES TECHNIQ
JI Microsc. Res. Tech.
PD JUN 1
PY 1995
VL 31
IS 2
BP 159
EP 173
DI 10.1002/jemt.1070310207
PG 15
WC Anatomy & Morphology; Biology; Microscopy
SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics;
   Microscopy
GA QY953
UT WOS:A1995QY95300006
PM 7655089
ER

PT J
AU BORKOWSKI, P
   ROBINSON, MJ
   KUSIAK, JW
   BORKOWSKI, A
   BRATHWAITE, C
   MERGNER, WJ
AF BORKOWSKI, P
   ROBINSON, MJ
   KUSIAK, JW
   BORKOWSKI, A
   BRATHWAITE, C
   MERGNER, WJ
TI STUDIES ON TGF-BETA-1 GENE-EXPRESSION IN THE INTIMA OF THE HUMAN AORTA
   IN REGIONS WITH HIGH AND LOW PROBABILITY OF DEVELOPING ATHEROSCLEROTIC
   LESIONS
SO MODERN PATHOLOGY
LA English
DT Article
DE ATHEROSCLEROSIS; HUMAN; AORTA; TRANSFORMING GROWTH FACTOR BETA-1;
   MESSENGER-RNA; IN SITU HYBRIDIZATION; COMPUTERIZED MORPHOMETRY
ID TRANSFORMING GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; FACTOR-AA-HOMODIMER;
   FACTOR-BETA; PROLIFERATION; INHIBITION; PATHOGENESIS
AB Certain regions of the human aorta are at greater risk for early and more severe atherosclerotic lesions development than others. Cornhill and coworkers (Cornhill FJ ct al.: Arteriosclerosis 5:415, 1985) created maps for the probability of developing atherosclerosis defining the high-probability region (HPR) in the dorsal descending thoracic aorta and the low-probability region (LPR) in the ventral descending thoracic aorta. Our study examines the hypothesis that transforming growth factor beta-1 (TGF-beta 1), a well-known suppressor of growth and function in many human cell lines, is one of the inhibitors of human atherogenesis. The present experiment analyzes the expression of mRNA for TGF-beta 1 in both the HPR and the LPR of aortas from young (age 17 to 25 y) males of black (n = 8) and white (n = 7) race. The level of TGF-beta 1 gene expression was assessed in the aortic intima in both the HPR and the LPR, using National Institutes of Health Image 1.47, an Apple Macintosh application capable of digital image processing, analysis, and morphometric measurement. There was significantly lower (P = 0.002, alpha = 0.05) TGF-beta 1 gene expression in the HPR than in the LPR in the 22- to 25-y age group. There was no significant difference in the 17- to 21-y age group and between the HPR and the LPR in the entire study group. We conclude that the decreased intimal TGF-1 gene expression suggests areas of lowered inhibitory activity for growth of human atherosclerotic plaques and therefore may have a direct relationship with the increased development of raised lesions in the HPR of the human aorta.
C1 MT SINAI MED CTR,DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140.
   UNIV MARYLAND,MED SYST,DEPT PATHOL,BALTIMORE,MD 21201.
   NIA,BALTIMORE,MD 21224.
NR 28
TC 23
Z9 23
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUN
PY 1995
VL 8
IS 5
BP 478
EP 482
PG 5
WC Pathology
SC Pathology
GA RD360
UT WOS:A1995RD36000005
PM 7675764
ER

PT J
AU LUJAN, HD
   MOWATT, MR
   CHEN, GZ
   NASH, TE
AF LUJAN, HD
   MOWATT, MR
   CHEN, GZ
   NASH, TE
TI ISOPRENYLATION OF PROTEINS IN THE PROTOZOAN GIARDIA-LAMBLIA
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE FARNESYLATION; GERANYLGERANYLATION; MEVALONATE PATHWAY; RAS PROTEIN;
   CHOLESTEROL SYNTHESIS
ID SELECTIVE-INHIBITION; SCHISTOSOMA-MANSONI; MEVALONATE PATHWAY; SERUM;
   BILE
AB We report the ability of Giardia lamblia to modify several of its cellular proteins by isoprenylation. Trophozoites cultured in the presence of [H-3]mevalonate synthesized radiolabeled proteins of approx. 50 and 21-26 kDa. Chemical analysis indicated that farnesyl and geranylgeranyl isoprenoids comprised the majority of the radiolabel covalently associated with trophozoite proteins. In addition, antibodies to human p21(ras) immunoprecipitated mevalonate-labelled species of approx. 21 kDa. Inhibitors of several enzymatic steps of the mevalonate pathway dramatically affected Giardia metabolism. Protein isoprenylation and cell growth were blocked by compactin and mevinolin, competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme in isoprenoid biosynthesis. In the presence of these inhibitors, Giardia growth was restored by the addition of mevalonate to the culture medium. In contrast, cell growth was blocked irreversibly by inhibitors of subsequent steps in the protein isoprenylation pathway. Trophozoite growth inhibition by limonene, perillic acid, perillyl alcohol and N-acetyl-S-farnesyl-L-cysteine was not reversed after the addition of mevalonate, dolichol, ubiquinone or cholesterol to the medium. These observations constitute the first description of protein isoprenylation in any protozoan and indicate that this post-translational modification is an important step in the regulation of the growth of this primitive eukaryote.
C1 MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48823.
RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA.
NR 43
TC 36
Z9 39
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD JUN
PY 1995
VL 72
IS 1-2
BP 121
EP 127
DI 10.1016/0166-6851(94)00070-4
PG 7
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA RV618
UT WOS:A1995RV61800012
PM 8538683
ER

PT J
AU WATERS, AP
   WHITE, W
   MCCUTCHAN, TF
AF WATERS, AP
   WHITE, W
   MCCUTCHAN, TF
TI THE STRUCTURE OF THE LARGE SUBUNIT RIBOSOMAL-RNA EXPRESSED IN BLOOD
   STAGES OF PLASMODIUM-FALCIPARUM
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE PLASMODIUM FALCIPARUM; MALARIA; LARGE SUBUNIT RIBOSOMAL RNA; INTERNAL
   TRANSCRIBED SPACER; DRUG RESISTANCE
ID RIBOSOMAL-RNA GENES; INTERNAL TRANSCRIBED SPACER-2;
   SACCHAROMYCES-CEREVISIAE; DNA; SEQUENCES; PARASITE; BERGHEI;
   IDENTIFICATION; RESISTANCE; PROTEINS
AB Here we present the sequence of the large subunit (LSU) rRNA expressed in blood-stage forms (and therefore A-type) of the malaria parasite, Plasmodium falciparum, from two different isolates. We determined the genomic sequence of a rRNA unit of the CAMP parasite strain from within the internal transcribed spacer 1 (ITS1) through the 5.8S rRNA gene, the ITS2 and the entire large subunit rRNA gene. We have also determined the corresponding sequence of the gene of the FVO strain by sequencing cDNA clones derived from blood-stage asexual parasites. Differences between the two were due to scattered point mutations in expansion segments of the mature rRNA regions. In addition to the point mutations, the rRNA genes from the two strains could be distinguished by the presence of a more complex polymorphism near the 3' end of the molecule. The most complex polymorphic form was localized on a single chromosome and found in only a subset of geographically distinct isolates. The sequences of the 5.8S rRNA unit and the LSU rRNA unit reported here can be logically assembled into a complete secondary structure which conforms to the standard structure conserved in all eukaryotic ribosomes. The construction of a model of secondary structure for the LSU rRNA has allowed the identification of phylogenetically conserved sequences involved in drug interaction with the ribosome, as well as those sequences involved in tertiary interactions within the rRNA itself.
C1 NIH,PARASIT DIS LAB,GROWTH & DEV SECT,BETHESDA,MD 20892.
   LEIDEN UNIV,PARASITOL LAB,LEIDEN,NETHERLANDS.
RI Waters, Andy/C-9377-2009
OI Waters, Andy/0000-0001-8900-2982
NR 33
TC 17
Z9 18
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD JUN
PY 1995
VL 72
IS 1-2
BP 227
EP 237
DI 10.1016/0166-6851(94)00077-Z
PG 11
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA RV618
UT WOS:A1995RV61800021
PM 8538692
ER

PT J
AU BARKSDALE, SK
   BAKER, CC
AF BARKSDALE, SK
   BAKER, CC
TI THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV PROTEIN AND THE
   REV-RESPONSIVE ELEMENT COUNTERACT THE EFFECT OF AN INHIBITORY 5'
   SPLICE-SITE IN A 3' UNTRANSLATED REGION
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID VIRAL MESSENGER-RNA; BOVINE PAPILLOMAVIRUS; GENE-PRODUCT; PREMESSENGER
   RNAS; CYTOPLASMIC RNA; U1A PROTEIN; EXPRESSION; POLYADENYLATION;
   SEQUENCES; TARGET
AB A 5' splice site located in a 3' untranslated region (3'UTR) has been shown previously to inhibit gene expression, Natural examples of inhibitory 5' splice sites have been identified in the late 3'UTRs of papillomaviruses and are thought to inhibit viral late gene expression at early stages of the viral life cycle. In this study, we demonstrate that the interaction of the human immunodeficiency virus type 1 Rev protein with the Rev-responsive element (RRE) overcomes the inhibitory effects of a 5' splice site located within a 3'UTR, This was studied by using both a bovine papillomavirus type 1 L1 cDNA expression vector and a chloramphenicol acetyltransferase expression vector containing a 5' splice site in the 3'UTR, In both systems, coexpression of Rev enhanced cytoplasmic expression from vectors containing the RRE even when the RRE and the inhibitory 5' splice site were separated by up to 1,000 nucleotides, In addition, multiple copies of a 5' splice site in a 3'UTR were shown to act synergistically, and this effect could also be moderated by the interaction of Rev and the RRE, These studies provide additional evidence that at least one mechanism of Rev action is through interactions,vith the splicing machinery. We have previously shown that base pairing between the U1 small nuclear RNA and a 3'UTR 5' splice site is required for inhibition of gene expression, However, experiments by J. Kjems and P. A. Sharp (J. Virol, 67:4769-4776, 1993) have suggested that Rev acts on spliceosome assembly at a stage after binding of the U1 small nuclear ribonucleoprotein to the 5' splice site, This finding suggests that binding of additional small nuclear ribonucleoproteins, as well as other splicing factors, may be necessary for the inhibitory action of a 3'UTR 5' splice site. These data also suggest that expression of the papillomavirus late genes in terminally differentiated keratinocytes can be regulated by a viral or cellular Rev-like activity.
C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892.
NR 63
TC 31
Z9 31
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 JUN
PY 1995
VL 15
IS 6
BP 2962
EP 2971
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500007
PM 7760794
ER

PT J
AU LEE, SST
   PINEAU, T
   DRAGO, J
   LEE, EJ
   OWENS, JW
   KROETZ, DL
   FERNANDEZSALGUERO, PM
   WESTPHAL, H
   GONZALEZ, FJ
AF LEE, SST
   PINEAU, T
   DRAGO, J
   LEE, EJ
   OWENS, JW
   KROETZ, DL
   FERNANDEZSALGUERO, PM
   WESTPHAL, H
   GONZALEZ, FJ
TI TARGETED DISRUPTION OF THE ALPHA-ISOFORM OF THE PEROXISOME
   PROLIFERATOR-ACTIVATED RECEPTOR GENE IN MICE RESULTS IN ABOLISHMENT OF
   THE PLEIOTROPIC EFFECTS OF PEROXISOME PROLIFERATORS
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ACYL-COA OXIDASE; ACID-BINDING-PROTEIN; BETA-OXIDATION PATHWAY; RAT
   HYDRATASE-DEHYDROGENASE; HIGH-FAT DIETS; OMEGA-HYDROXYLASE; CLOFIBRIC
   ACID; 3-KETOACYL-COA THIOLASE; BIFUNCTIONAL ENZYME; HEPATIC PEROXISOMES
AB To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted the ligand-binding domain of the or isoform of mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for the mutation lack expression of mPPAR alpha protein and yet are viable and fertile and exhibit no detectable gross phenotypic defects, Remarkably, these animals do not display the peroxisome proliferator pleiotropic response when challenged with the classical peroxisome proliferators, clofibrate and Wy-14,643, Following exposure to these chemicals, hepatomegaly, peroxisome proliferation, and transcriptional activation of target genes were not observed. These results clearly demonstrate that mPPAR alpha is the major isoform required for mediating the pleiotropic response resulting from the actions of peroxisome proliferators. mPPAR alpha-deficient animals should prove useful to further investigate the role of this receptor in hepatocarcinogenesis, fatty acid metabolism, and cell cycle regulation.
C1 NICHHD,BETHESDA,MD 20892.
   NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,LAB SCI SECT,BETHESDA,MD 20892.
RP LEE, SST (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA.
NR 75
TC 1226
Z9 1243
U1 1
U2 13
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 JUN
PY 1995
VL 15
IS 6
BP 3012
EP 3022
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500012
PM 7539101
ER

PT J
AU REINHOLD, W
   EMENS, L
   ITKES, A
   BLAKE, M
   ICHINOSE, I
   ZAJAC-KAYE, M
AF REINHOLD, W
   EMENS, L
   ITKES, A
   BLAKE, M
   ICHINOSE, I
   ZAJAC-KAYE, M
TI THE MYC INTRON-BINDING POLYPEPTIDE ASSOCIATES WITH RFX1 IN-VIVO AND
   BINDS TO THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II PROMOTER REGION,
   TO THE HEPATITIS-B VIRUS ENHANCER, AND TO REGULATORY REGIONS OF SEVERAL
   DISTINCT VIRAL GENES
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID DR-ALPHA GENE; NUCLEAR PROTEINS; 1ST INTRON; SEQUENCES; CELLS; SITE;
   TRANSCRIPTION; INITIATION; EXPRESSION; DOMAIN
AB We demonstrated that MIF-1, identified initially as a binding activity that associated with the intron I element of the c-myc gene, consists of two polypeptides, the myc intron-binding peptide (MIBP1) and the major histocompatibility class II promoter-binding protein, RFX1. Using a polyclonal antiserum directed against either oligonucleotide affinity-purified MIBP1 or a peptide derived from RFX1, we showed that MIBP1 and RFX1 are distinct molecules that associate in vivo and are both present in DNA-protein complexes at the c-myc (MIF-1) and major histocompatibility complex class II (RFX1) binding sites. We have also found that MIBP1 and RFX1 bind to a regulatory site (termed EP) required for enhancer activity of hepatitis B virus. In addition, we have identified MIF-1-like sequences within regulatory regions of several other viral genes and have shown that MIBP1 binds to these sites in cytomegalovirus, Epstein-Barr virus, and polyomavirus. We have also demonstrated that the MIF-1 and EP elements can function as silencers in the hepatocarcinoma HepG2 and the cervical carcinoma HeLa cell lines. These findings indicate that MIBP1 and EP/RFX1 can associate in vivo and may regulate the expression of several distinct cellular and viral genes.
C1 NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BIOL CHEM LAB, BETHESDA, MD 20892 USA.
NR 38
TC 39
Z9 42
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 1995
VL 15
IS 6
BP 3041
EP 3048
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500015
PM 7760800
ER

PT J
AU UMLAUF, SW
   BEVERLY, B
   LANTZ, O
   SCHWARTZ, RH
AF UMLAUF, SW
   BEVERLY, B
   LANTZ, O
   SCHWARTZ, RH
TI REGULATION OF INTERLEUKIN-2 GENE-EXPRESSION BY CD28 COSTIMULATION IN
   MOUSE T-CELL CLONES - BOTH NUCLEAR AND CYTOPLASMIC RNAS ARE REGULATED
   WITH COMPLEX KINETICS
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID LYMPHOKINE MESSENGER-RNA; ACCESSORY MOLECULE CD28; CTLA-4
   COUNTER-RECEPTOR; LYMPHOCYTES-T; ANTIGEN PRESENTATION; ACTIVATION
   PATHWAY; IL-2 GENE; STIMULATION; INDUCTION; SIGNALS
AB T-cell receptor (TCR) signalling is required to induce expression of the interleukin 2 (IL-2) gene in mouse T cells. Additional costimulation through CD28 augments IL-2 production by 30- to 100-fold. Using IL-2 RNA accumulation and transcription reporter assays, we have addressed potential mechanisms of CD28 regulation at various time points of stimulation. The kinetic regulation of IL-2 mRNA by TCR and CD28 signals is complex: (i) at the earliest detectable time point, CD28 signalling causes a 20-fold increase compared with TCR signalling alone; (ii) both groups rapidly accumulate mRNA for the first 4 h; (iii) IL-2 mRNA then disappears from cells stimulated through the TCR alone but plateaus or increases slightly in cells costimulated through CD28; and (iv) after 8 h, the mRNA disappears in cultures with the anti-CD28 antibody. Transcription reporter assays did not show a specific effect of CD28 signalling on IL-2 enhancer driven transcription. This was true for either a 353- or a 1.9-kb enhancer, over a broad range of kinetics and TCR occupancy, and with several TCR signal mimics. The early component of CD28 costimulation is nuclear, however, since the initial enhancement of mRNA is also found in unspliced IL-2 RNA. Between 2 and 6 h, there is a marked difference in the rates of decay of IL-2 mRNA in the presence and absence of the CD28 signalling. Rapid decay of IL-2 mRNA commences after 8 h even in the presence of CD28 signals, although the decay occurs at a rate slower than that seen after 4 h of anti-TCR stimulation alone. This complexity suggests the existence of two interesting molecular mechanisms by which CD28 costimulates lymphokine gene expression.
C1 NIH,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892.
   ANERGEN INC,REDWOOD CITY,CA 94063.
RI Lantz, Olivier/J-4960-2012
OI Lantz, Olivier/0000-0003-3161-7719
NR 40
TC 82
Z9 82
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 1995
VL 15
IS 6
BP 3197
EP 3205
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500032
PM 7539104
ER

PT J
AU LEVIN, HL
AF LEVIN, HL
TI A NOVEL MECHANISM OF SELF-PRIMED REVERSE TRANSCRIPTION DEFINES A NEW
   FAMILY OF RETROELEMENTS
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; CELL-FREE SYNTHESIS; RNA-LINKED MSDNA; FISSION
   YEAST; TY1 TRANSPOSITION; SCHIZOSACCHAROMYCES-POMBE; ELEMENT
   TRANSPOSITION; DNA-SYNTHESIS; RETROTRANSPOSITION
AB Retroviruses and long terminal repeat (LTR)-containing retrotransposons initiate reverse transcription by using a specific tRNA primer that anneals to the primer-binding site of the retroelement transcript. Sequences from a large number of retroviruses and LTR-containing retrotransposons had indicated that the role of tRNAs in priming reverse transcription is universal among these LTR-containing retroelements. Data presented here strongly support the surprising conclusion that Tf1, a highly active LTR-containing retrotransposon isolated from Schizosaccharomyces pombe, undergoes a novel self-priming process that requires hybridization between the primer-binding site and the first II bases of the Tf1 transcript. Single-base mutations in these regions block transposition and reverse transcription, while compensatory mutations that reestablish complementarity rescue both defects. In addition, the sequence of the minus-strand RNA primer of reverse transcription was consistent with its being derived from the 5' end of the Tf1 transcript, Evidence that this mechanism defines a new family of retroelements is presented.
RP NICHHD, MOLEC GENET LAB, BETHESDA, MD 20892 USA.
NR 29
TC 64
Z9 66
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 1995
VL 15
IS 6
BP 3310
EP 3317
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500044
PM 7760826
ER

PT J
AU QUELLE, FW
   SHIMODA, K
   THIERFELDER, W
   FISCHER, C
   KIM, A
   RUBEN, SM
   CLEVELAND, JL
   PIERCE, JH
   KEEGAN, AD
   NELMS, K
   PAUL, WE
   IHLE, JN
AF QUELLE, FW
   SHIMODA, K
   THIERFELDER, W
   FISCHER, C
   KIM, A
   RUBEN, SM
   CLEVELAND, JL
   PIERCE, JH
   KEEGAN, AD
   NELMS, K
   PAUL, WE
   IHLE, JN
TI CLONING OF MURINE STAT6 AND HUMAN STAT6, STAT PROTEINS THAT ARE
   TYROSINE-PHOSPHORYLATED IN RESPONSES TO IL-4 AND IL-3 BUT ARE NOT
   REQUIRED FOR MITOGENESIS
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RECEPTOR GAMMA-CHAIN; SIGNAL-TRANSDUCTION; ERYTHROPOIETIN RECEPTOR;
   INTERLEUKIN-4 RECEPTOR; HEMATOPOIETIC-CELLS; IDENTIFICATION; LEUKEMIA;
   LINE
AB By searching a database of expressed sequences, we identified a member of the signal transducers and activators of transcription (Stat) family of proteins, Human and murine full-length cDNA clones were obtained and sequenced, The sequence of the human cDNA was identical to the recently published sequence for interleukin-4 (IL-4)-Stat (J. Hou, U. Schindler, W. J. Henzel, T. C. Ho, M. Brasseur, and S. L. McKnight, Science 265:1701-1706, 1994), while the murine Stat6 amino acid and nucleotide sequences were 83 and 84% identical to the human sequences, respectively. Using Stat6-specific antiserum, we demonstrated that Stat6 is rapidly tyrosine phosphorylated following stimulation of appropriate cell lines with IL-4 or IL-3 but is not detectably phosphorylated following stimulation with IL-2, IL-12, or erythropoietin. In contrast, IL-2, IL-3, and erythropoietin induce the tyrosine phosphorylation of Stat5 while IL-12 uniquely induces the tyrosine phosphorylation of Stat4. Inducible tyrosine phosphorylation of Stat6 requires the membrane-distal region of the IL-4 receptor or chain, This region of the receptor is not required for cell growth, demonstrating that Stat6 tyrosine phosphorylation does not contribute to mitogenesis.
C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA.
   HUMAN GENOME SCI INC, ROCKVILLE, MD 20850 USA.
   NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA.
   NIAID, BETHESDA, MD 20892 USA.
   UNIV TENNESSEE, SCH MED, DEPT BIOCHEM, MEMPHIS, TN 38163 USA.
FU NCI NIH HHS [P30 CA21765]; NHLBI NIH HHS [P01 HL53749]; NIDDK NIH HHS
   [R01 DK44158]
NR 59
TC 277
Z9 284
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 1995
VL 15
IS 6
BP 3336
EP 3343
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500047
PM 7760829
ER

PT J
AU MICHAUD, NR
   FABIAN, JR
   MATHES, KD
   MORRISON, DK
AF MICHAUD, NR
   FABIAN, JR
   MATHES, KD
   MORRISON, DK
TI 14-3-3 IS NOT ESSENTIAL FOR RAF-1 FUNCTION - IDENTIFICATION OF RAF-1
   PROTEINS THAT ARE BIOLOGICALLY ACTIVATED IN A 14-3-3-INDEPENDENT AND
   RAS-INDEPENDENT MANNER
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SIGNAL TRANSDUCTION; MAP KINASE; PHOSPHORYLATION; DOWNSTREAM; C-RAF-1;
   FAMILY; REQUIREMENT; DEFINITION; P21(RAS); REGION
AB Recent reports have demonstrated the in vivo association of Raf-1 with members of the 14-3-3 protein family. To address the significance of the Raf-1-14-3-3 interaction, we investigated the enzymatic activity and biological function of Raf-1 in the presence and absence of associated 14-3-3. The interaction between these two molecules was disrupted in vivo and in vitro with a combination of molecular and biochemical techniques. Biochemical studies demonstrated that the enzymatic activities of Raf-1 were equivalent in the presence and absence of 14-3-3. Furthermore, mixing of purified Raf-1 and 14-3-3 in vitro was not sufficient to activate Raf-1, With a molecular approach, Cys-165 and Cys-168 as well as Ser-259 were identified as residues of Raf-1 required for the interaction with 14-3-3, Cys-165 and Cys-168 are located within the conserved cysteine-rich region of the CR1 domain, and Ser-259 is a conserved site of serine phosphorylation found within the CR2 domain. Mutation of either Cys-165 and Cys-168 or Ser-259 prevented the stable interaction of Raf-1 with 14-3-3 in vivo, Consistent with the model in which a site of serine phosphorylation is involved in the Raf-1-14-3-3 interaction, dephosphorylated Raf-l was unable to associate with 14-3-3 in vitro. Phosphorylation may represent a general mechanism mediating 14-3-3 binding, because dephosphorylation of the Bcr kinase (known to interact with 14-3-3) also eliminated its association with 14-3-3, Finally, mutant Raf-1 proteins unable to stably interact with 14-3-3 exhibited enhanced enzymatic activity in human 293 cells and Xenopus oocytes and were biologically activated, as demonstrated by their ability to induce meiotic maturation of Xenopus oocytes, However, in contrast to wild-type Raf-1, activation of these mutants was independent of Ras, Our results therefore indicate that interaction with 14-3-3 is not essential for Raf-1 function.
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC MECHANISMS CARCINOGENESIS LAB,FREDERICK,MD 21702.
FU NCI NIH HHS [N01-CO-46000]
NR 50
TC 179
Z9 180
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 JUN
PY 1995
VL 15
IS 6
BP 3390
EP 3397
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ325
UT WOS:A1995QZ32500053
PM 7760835
ER

PT J
AU SHENG, HZ
   LIN, PX
   NELSON, PG
AF SHENG, HZ
   LIN, PX
   NELSON, PG
TI COMBINATORIAL EXPRESSION OF IMMEDIATE-EARLY GENES IN SINGLE NEURONS
SO MOLECULAR BRAIN RESEARCH
LA English
DT Article
DE PCR; SINGLE CELL; IEG/DRG NEURON
ID CALCIUM CHANNELS; C-FOS; COMPLEXES; ACTIVATION; CELLS
AB To address the question how relatively small numbers of immediate early gene (IEG) could specifically couple a wide range of stimulus-response cascades, we examined the possibility that IEG could be expressed heterogeneously in individual neurons. Analysis of multiple IEG in single neurons revealed that many individual DRG neurons express several IEGs. The combinatorial expression of IEGs by individual DRG displays substantial heterogeneity. Analysis of mRNA species encoding AP-1 composition in single cells also revealed coordinated change of mRNAs coding for AP-1 factors after membrane depolarization. Our results indicate that differential expression of IEG in individual cells, and the possible interaction among them may represent a mechanism by which the specificity in stimulation-response coupling may be achieved by IEGs.
RP SHENG, HZ (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 6B,ROOM 2B-211,BETHESDA,MD 20892, USA.
NR 24
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-328X
J9 MOL BRAIN RES
JI Mol. Brain Res.
PD JUN
PY 1995
VL 30
IS 2
BP 196
EP 202
DI 10.1016/0169-328X(94)00291-L
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA RA068
UT WOS:A1995RA06800002
ER

PT J
AU DONOVAN, DM
   VANDENBERGH, DJ
   PERRY, MP
   BIRD, GS
   INGERSOLL, R
   NANTHAKUMAR, E
   UHL, GR
AF DONOVAN, DM
   VANDENBERGH, DJ
   PERRY, MP
   BIRD, GS
   INGERSOLL, R
   NANTHAKUMAR, E
   UHL, GR
TI HUMAN AND MOUSE DOPAMINE TRANSPORTER GENES - CONSERVATION OF 5'-FLANKING
   SEQUENCE ELEMENTS AND GENE STRUCTURES
SO MOLECULAR BRAIN RESEARCH
LA English
DT Article
DE TRANSPORTER; PROMOTER; GENE; PARKINSONS DISEASE; COCAINE
ID NEURON-SPECIFIC EXPRESSION; NEUROTRANSMITTER TRANSPORTERS;
   TYROSINE-HYDROXYLASE; CLONING; COCAINE; DNA; TRANSCRIPTION; DISPLAYS;
   PROTEIN; REGION
AB Synaptic reaccumulation of the neurotransmitter dopamine is mediated by the dopamine transporter (DAT), a member of the family of twelve transmembrane domain, sodium- and chloride-dependent neurotransmitter transporters. Several DAT features, including its exclusive expression in dopaminergic neurons, implication in cocaine action, and prominent role in the mechanisms of Parkinsonism-inducing neurotoxins, make understanding of the DAT gene of interest. Isolation and characterization of the human and mouse DAT genes has allowed elucidation of similarities between each and other members of this transporter gene family. Sequences 5' to transcriptional start sites contain G-C rich, TATA-less, CAAT-less regions with striking conservation between human and mouse gene flanking regions. These studies suggest sequence elements that are candidates to contribute to the dopamine transporter's dopaminergic cell-specific expression.
C1 MOLEC NEUROBIOL BRANCH, BALTIMORE, MD 21224 USA.
   NIDA, ADDICT RES CTR, DIV INTRAMURAL RES, OFF DIRECTOR, BALTIMORE, MD 21224 USA.
   GENET CORE FACIL, BALTIMORE, MD 21205 USA.
   JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA.
   JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA.
NR 45
TC 51
Z9 54
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-328X
J9 MOL BRAIN RES
JI Mol. Brain Res.
PD JUN
PY 1995
VL 30
IS 2
BP 327
EP 335
DI 10.1016/0169-328X(95)00018-N
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA RA068
UT WOS:A1995RA06800015
ER

PT J
AU UEDA, M
   KAWAMURA, H
   SUTTER, C
   GLICK, A
   YUSPA, SH
   STRICKLAND, JE
AF UEDA, M
   KAWAMURA, H
   SUTTER, C
   GLICK, A
   YUSPA, SH
   STRICKLAND, JE
TI ANALYSIS OF V-HA-RAS AND V-FOS ONCOGENE TRANSDUCTION INTO A MOUSE
   EPIDERMAL-CELL LINE WITH INITIATED PHENOTYPE IN CULTURE BUT NORMAL SKIN
   PHENOTYPE IN-VIVO
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE SKIN GRAFTING; HA-RAS; FOS; KERATINOCYTE; TERMINAL DIFFERENTIATION
ID TERMINAL DIFFERENTIATION; ABERRANT EXPRESSION; TUMOR PROGRESSION;
   KERATIN K13; CARCINOGENESIS; MARKERS; PAPILLOMAS; INVITRO; GRAFTS; GENE
AB Cell line SCR722 was derived from adult SENCAR mouse epidermal cells initiated in culture by treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine and selection for foci proliferating in medium with calcium levels that induce terminal differentiation in normal cells. Expansion of one of these foci and two additional cell clonings produced cell line SCR722, which was near-tetraploid and formed normal skin when grafted to athymic nude mouse hosts. However, unlike normal keratinocytes, SCR722 cells fail to suppress papilloma formation when grafted along with papilloma cell line SP-l. For optimum growth in culture, SCR722 cells required fibroblast-conditioned medium and 0.5 mM Ca2+. SCR722 cells had a wild-type c-Ha-ras gene but had lost their requirement for conditioned medium in culture and produced dysplastic papillomas in grafts when transduced with the v-Ha-ras gene. SCR722 cells stably expressing the v-fos gene produced normal epidermis in grafts, but when these cells were transduced with the v-Ha-ras gene, they produced carcinomas. Clones with greater expression of the transfected v-fos gene had a more invasive phenotype in vivo. These results indicate that carcinogen treatment of epithelial cells can result in an altered but nontumorigenic phenotype that may be at risk for becoming a more advanced neoplastic state with additional genetic alterations. (C) 1995 Wiley-Liss, Inc.*
C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892.
NR 36
TC 1
Z9 1
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD JUN
PY 1995
VL 13
IS 2
BP 96
EP 103
DI 10.1002/mc.2940130206
PG 8
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA RG633
UT WOS:A1995RG63300005
PM 7605585
ER

PT J
AU MCKNIGHT, RA
   SPENCER, M
   DITTMER, J
   BRADY, JN
   WALL, RJ
   HENNIGHAUSEN, L
AF MCKNIGHT, RA
   SPENCER, M
   DITTMER, J
   BRADY, JN
   WALL, RJ
   HENNIGHAUSEN, L
TI AN ETS SITE IN THE WHEY ACIDIC PROTEIN GENE PROMOTER MEDIATES
   TRANSCRIPTIONAL ACTIVATION IN THE MAMMARY-GLAND OF PREGNANT MICE BUT IS
   DISPENSABLE DURING LACTATION
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID TRANSGENIC MICE; BINDING-SITES; EXPRESSION; HORMONE; DNA; ELEMENTS;
   REGION; CELLS; MOTIF
AB The whey acidic protein (WAR) gene is specifically expressed in mammary tissue, and its transcription is,induced several thousand-fold during pregnancy and remains high throughout lactation. A purine-rich sequence (PRS) located around -110 of the WAP gene promoter is conserved between mice, rats, and rabbits, suggesting that it features a regulatory element. This PRS contains an invariant GGAA/T core motif characteristic of the binding site for Ets transcription factors. Electromobility shift assays demonstrate that Ets1 binds specifically to the PRS. Experiments in transgenic mice further demonstrate that this PRS/Ets site plays a critical role in the activation of WAP transgenes during pregnancy, but that its presence is not required for high expression throughout lactation. Transgenes with an intact PRS/Ets site are expressed at high levels at day 13 of pregnancy, with little further increase during late pregnancy and lactation. In contrast, WAP transgenes with a mutation in the PRS/Ets site, which abrogates the binding of Ets1, are not expressed at midpregnancy, but their transcriptional activity is not affected during lactation. These results demonstrate that Ets-signaling pathways can function as stage-specific transcriptional activators of milk protein genes in the developing mammary gland. In addition, this work extends earlier findings that gene activation during pregnancy and lactation is mediated, in part, by different mechanisms.
C1 NIDDKD, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA.
   USDA ARS, BELTSVILLE, MD 20725 USA.
   NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA.
RI Dittmer, Juergen/G-1160-2011
NR 36
TC 20
Z9 21
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 JUN
PY 1995
VL 9
IS 6
BP 717
EP 724
DI 10.1210/me.9.6.717
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA RB545
UT WOS:A1995RB54500007
PM 8592517
ER

PT J
AU MILLER, CE
   HUPPI, K
   SIWARSKI, D
   KARPAS, A
   NEWMAN, A
   MAINHART, C
   GLAUDEMANS, CPJ
AF MILLER, CE
   HUPPI, K
   SIWARSKI, D
   KARPAS, A
   NEWMAN, A
   MAINHART, C
   GLAUDEMANS, CPJ
TI A MURINE ANTIBODY TO SHIGELLA-DYSENTERIAE TYPE-1 EMPLOYS V-GENES THAT
   CONTAIN A REARRANGED CODON FOR THE LAMBDA-LIGHT-CHAIN
SO MOLECULAR IMMUNOLOGY
LA English
DT Note
ID INFECTIONS
AB The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707 E9) has been cloned, and sequenced. Binding patterns with fragments of the bacterial polysaccharide antigen had already been studied in detail. The VH sequence utilizes the VH441 gene, first identified amongst beta-(1,6)galactan-binding antibodies, while the VL is closely related to the V lambda 1 gene. We found that the VL(3707) (E9) gene employed a VL-J combinatorial joining leading to a rare Trp-->Leu substitution at position L96.
C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892.
   NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892.
   NIH,US FDA,CTR BIOL RES & REVIEW,BETHESDA,MD 20892.
NR 13
TC 3
Z9 4
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD JUN
PY 1995
VL 32
IS 9
BP 679
EP 682
DI 10.1016/0161-5890(95)00072-M
PG 4
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA RM056
UT WOS:A1995RM05600009
PM 7643860
ER

PT J
AU DANESI, R
   FIGG, WD
   REED, E
   MYERS, CE
AF DANESI, R
   FIGG, WD
   REED, E
   MYERS, CE
TI PACLITAXEL (TAXOL) INHIBITS PROTEIN ISOPRENYLATION AND INDUCES APOPTOSIS
   IN PC-3 HUMAN PROSTATE-CANCER CELLS
SO MOLECULAR PHARMACOLOGY
LA English
DT Note
ID D-LIMONENE; GROWTH; PROLIFERATION; LOVASTATIN; DEATH; ASSAY
AB Paclitaxel was examined for its effects on cell survival, internucleosomal DNA fragmentation, and protein isoprenylation in the human prostate cancer cell line PC-3. Treatment of cells with paclitaxel at 5-60 nM for 24 hr resulted in a dose-dependent inhibition of cell viability (IC50, 31.2 nM), which was partially prevented by supplementing the cell culture medium with two nonsterol polyisoprenyl compounds, farnesyl-pyrophosphate (-PP) and geranylgeranyl-PP (3 mu M each). Furthermore, agarose gel electrophoresis of DNA extracted from cells treated with paclitaxel (15-60 nM) for 24 hr showed DNA laddering with production of fragments of 180-base pair multiples, indicating the occurrence of apoptotic cell death. Internucleosomal DNA fragmentation by paclitaxel was also detected by a photometric enzyme immunoassay using antihistone antibodies; if culture medium was supplemented with farnesyl-PP and geranylgeranyl-PP (3 mu M each), a reduction in mono- and oligoucleosome production was observed. The post-translational incorporation of metabolites of (RS)-[5-H-3]mevalonolactone (100 mu Ci/ml) into prenylated proteins of PC-3 cells was inhibited by paclitaxel at 30 and 60 nM. In addition, the immunoprecipitation of p21ras and p21rap-1 proteins from PC-3 cells exposed to paclitaxel (30 and 60 nM) and labeled with (RS)-[5-H-3]mevalonolactone showed a substantial inhibition of the incorporation of farnesyl and geranylgeranyl prenoid groups, respectively, into the aforementioned proteins. These results indicate that the inhibition of protein isoprenylation is a novel component of the complex biochemical effects of the drug and plays an important role in the mechanism of paclitaxel cytotoxicity in PC-3 cells.
C1 UNIV VIRGINIA,DIV HEMATOL ONCOL,CHARLOTTESVILLE,VA 22908.
   NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892.
RI Figg Sr, William/M-2411-2016
NR 30
TC 61
Z9 61
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 JUN
PY 1995
VL 47
IS 6
BP 1106
EP 1111
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RG100
UT WOS:A1995RG10000004
PM 7603448
ER

PT J
AU BENCHEKROUN, MN
   PARKER, R
   DABHOLKAR, M
   REED, E
   SINHA, BK
AF BENCHEKROUN, MN
   PARKER, R
   DABHOLKAR, M
   REED, E
   SINHA, BK
TI EFFECTS OF INTERLEUKIN-1-ALPHA ON DNA-REPAIR IN HUMAN OVARIAN-CARCINOMA
   (NIH-OVCAR-3) CELLS - IMPLICATIONS IN THE MECHANISM OF SENSITIZATION OF
   CIS-DIAMMINEDICHLOROPLATINUM(II)
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID HUMAN-MELANOMA CELLS; SYNERGISTIC ANTITUMOR-ACTIVITY; MURINE
   LEUKEMIA-L1210 CELLS; LINE NIH-OVCAR-3; CISPLATIN CHEMOTHERAPY;
   CROSS-LINKING; CYTO-TOXICITY; RESISTANCE; PLATINUM; ETOPOSIDE
AB The cytokine interleukin-1 alpha (IL-1 alpha) showed a cytostatic effect on human ovarian carcinoma cells and significantly enhanced the antiproliferative activity of cis-diamminedichloroplatinum(II) (cisplatin) toward the NIH:OVCAR-3 tumor cell line in culture. The factor of sensitization was 15-20-fold. The maximum levels of sensitization were observed both with simultaneous exposure to cisplatin and IL-1 alpha and with 24-hr pretreatment with IL-1 alpha. Synergy between these agents was diminished when cells were pretreated with an IL-1 alpha-specific receptor antagonist, indicating that synergistic interaction was receptor mediated. Using atomic absorption spectroscopy, we evaluated the cellular accumulation of cisplatin and the DNA platination; the results showed that IL-1 alpha increased cellular accumulation of cisplatin and DNA platination. Cisplatin did not affect IL-1 alpha accumulation in NIH:OVCAR-3 cells. Further studies showed that IL-1 alpha reduced the removal of platinum from DNA. These results strongly suggest that IL-1 alpha inhibits DNA repair, and this decrease in DNA repair may explain, in part, the strong synergistic interaction between IL-1 alpha and cisplatin in NIH:OVCAR-3 cells.
C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892.
NR 44
TC 11
Z9 11
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 JUN
PY 1995
VL 47
IS 6
BP 1255
EP 1260
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RG100
UT WOS:A1995RG10000024
PM 7603468
ER

PT J
AU HILL, A
   JUGOVIC, P
   YORK, I
   RUSS, G
   BENNINK, J
   YEWDELL, J
   PLOEGH, H
   JOHNSON, D
AF HILL, A
   JUGOVIC, P
   YORK, I
   RUSS, G
   BENNINK, J
   YEWDELL, J
   PLOEGH, H
   JOHNSON, D
TI HERPES-SIMPLEX VIRUS TURNS OFF THE TAP TO EVADE HOST IMMUNITY
SO NATURE
LA English
DT Article
ID PEPTIDE TRANSLOCATION; ENDOPLASMIC-RETICULUM; TRANSPORTER; CHAINS;
   CONSTRUCTION; EXPRESSION; MOLECULES; VARIANTS; HEAVY
AB MANY viruses have evolved mechanisms to avoid detection by the host immune system, Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells(1). The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum(1,2), and the heavy chain and beta(2)-microglubulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides(1). We show here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.
C1 MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON L8N 325,CANADA.
   NIAID,VIRAL DIS LAB,BETHESDA,MD 20892.
RP HILL, A (reprint author), MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139, USA.
RI yewdell, jyewdell@nih.gov/A-1702-2012; 
OI York, Ian/0000-0002-3478-3344
NR 29
TC 670
Z9 676
U1 8
U2 32
PU MACMILLAN MAGAZINES LTD
PI LONDON
PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 1
PY 1995
VL 375
IS 6530
BP 411
EP 415
DI 10.1038/375411a0
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RB101
UT WOS:A1995RB10100055
PM 7760935
ER

PT J
AU HENGGE, UR
   CHAN, EF
   FOSTER, RA
   WALKER, PS
   VOGEL, JC
AF HENGGE, UR
   CHAN, EF
   FOSTER, RA
   WALKER, PS
   VOGEL, JC
TI CYTOKINE GENE-EXPRESSION IN EPIDERMIS WITH BIOLOGICAL EFFECTS FOLLOWING
   INJECTION OF NAKED DNA
SO NATURE GENETICS
LA English
DT Article
ID ATTRACTANT ACTIVATION PROTEIN-1; BETA-GALACTOSIDASE; IMMUNE-RESPONSES;
   MOUSE MUSCLE; PLASMID DNA; KERATINOCYTES; CELLS; THERAPY; MICE; VACCINES
AB The epidermis is readily accessible for genetic manipulation and is easily monitored. Using pig skin because it is very similar to human skin morphologically, we have developed a method to transiently express biologically active factors in epidermis. Following direct injection of naked plasmid DNA into skin, DNA is taken up and transiently expressed at high levels by epidermal keratinocytes. Injection of interleukin-8 plasmid DNA into skin results in the appropriate biological response of neutrophil recruitment, demonstrating functional utility. In addition to this model's therapeutic uses, the biological effects of structural gene products on the epidermis could also be studied in vivo.
C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892.
NR 34
TC 204
Z9 206
U1 0
U2 2
PU NATURE PUBLISHING CO
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 1995
VL 10
IS 2
BP 161
EP 166
DI 10.1038/ng0695-161
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA RA857
UT WOS:A1995RA85700012
PM 7545056
ER

PT J
AU WANG, XW
   YEH, H
   SCHAEFFER, L
   ROY, R
   MONCOLLIN, V
   EGLY, JM
   WANG, Z
   FRIEDBERG, EC
   EVANS, MK
   TAFFE, BG
   BOHR, VA
   WEEDA, G
   HOEIJMAKERS, JHJ
   FORRESTER, K
   HARRIS, CC
AF WANG, XW
   YEH, H
   SCHAEFFER, L
   ROY, R
   MONCOLLIN, V
   EGLY, JM
   WANG, Z
   FRIEDBERG, EC
   EVANS, MK
   TAFFE, BG
   BOHR, VA
   WEEDA, G
   HOEIJMAKERS, JHJ
   FORRESTER, K
   HARRIS, CC
TI P53 MODULATION OF TFIIH-ASSOCIATED NUCLEOTIDE EXCISION-REPAIR ACTIVITY
SO NATURE GENETICS
LA English
DT Article
ID WILD-TYPE P53; COMPLEMENTATION GROUP-D; XERODERMA-PIGMENTOSUM;
   DNA-REPAIR; GENE AMPLIFICATION; COCKAYNE SYNDROME; PROTEIN; REPLICATION;
   HELICASE; TRANSCRIPTION
AB p53 has pleiotropic functions including control of genomic plasticity and integrity. Here we report that p53 can bind to several transcription factor IIH-associated factors, including transcription-repair factors, XPD (Rad3) and XPB, as well as CSB involved in strand-specific DNA repair, via its C-terminal domain. We also found that wild-type, but not Arg273His mutant p53 inhibits XPD (Rad3) and XPB DNA helicase activities. Moreover, repair of UV-induced dimers is slower in Li-Fraumeni syndrome cells (heterozygote p53 mutant) than in normal human cells. Our findings indicate that p53 may play a direct role in modulating nucleotide excision repair pathways.
C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892.
   FAC MED STRASBOURG,INSERM,U184,CNRS,UPR 6520,F-67085 STRASBOURG,FRANCE.
   UNIV TEXAS,SW MED CTR,DEPT PATHOL,MOLEC PATHOL LAB,DALLAS,TX 75235.
   NIA,MOLEC GENET LAB,BALTIMORE,MD 21224.
   ERASMUS UNIV ROTTERDAM,CTR MED GENET,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS.
RI Wang, Xin/B-6162-2009
NR 61
TC 481
Z9 487
U1 0
U2 8
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 JUN
PY 1995
VL 10
IS 2
BP 188
EP 195
DI 10.1038/ng0695-188
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA RA857
UT WOS:A1995RA85700016
PM 7663514
ER

PT J
AU ROSENBERG, HF
   DYER, KD
   TIFFANY, HL
   GONZALEZ, M
AF ROSENBERG, HF
   DYER, KD
   TIFFANY, HL
   GONZALEZ, M
TI RAPID EVOLUTION OF A UNIQUE FAMILY OF PRIMATE RIBONUCLEASE GENES
SO NATURE GENETICS
LA English
DT Article
ID EOSINOPHIL CATIONIC PROTEIN; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING;
   NEUROTOXIN; CDNA; NUCLEOTIDE; HOMOLOGY
AB We have traced the rapid molecular evolution of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), two host defense proteins that are members of the mammalian ribonuclease gene family. The EDN/ECP gene pair arose from a recent duplication event that occurred after the divergence of New World and Old World monkeys. Since duplication, the genes encoding EDN and ECP have accumulated nonsilent mutations at rates exceeding those of all other functional coding sequences studied in primates, while retaining both the structural and catalytic components required for ribonuclease activity. These results suggest that both EDN and ECP may be responding to unusual evolutionary constraints, which has prompted a reexamination of their physiologic function.
C1 GEORGE WASHINGTON UNIV,GRAD PROGRAM GENET,WASHINGTON,DC 20052.
RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 34
TC 114
Z9 124
U1 0
U2 4
PU NATURE PUBLISHING CO
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 1995
VL 10
IS 2
BP 219
EP 223
DI 10.1038/ng0695-219
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA RA857
UT WOS:A1995RA85700021
PM 7663519
ER

PT J
AU POLYMEROPOULOS, MH
   DELUNA, RIO
   IDE, SE
   TORRES, R
   RUBENSTEIN, J
   FRANCOMANO, CA
AF POLYMEROPOULOS, MH
   DELUNA, RIO
   IDE, SE
   TORRES, R
   RUBENSTEIN, J
   FRANCOMANO, CA
TI THE GENE FOR PYCNODYSOSTOSIS MAPS TO HUMAN-CHROMOSOME 1CEN-Q21
SO NATURE GENETICS
LA English
DT Note
C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892.
   HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,MEXICO CITY,DF,MEXICO.
RP POLYMEROPOULOS, MH (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892, USA.
NR 11
TC 37
Z9 38
U1 0
U2 0
PU NATURE PUBLISHING CO
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 1995
VL 10
IS 2
BP 238
EP 239
DI 10.1038/ng0695-238
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA RA857
UT WOS:A1995RA85700025
PM 7663522
ER

PT J
AU MCDOWELL, GA
   GAHL, WA
   STEPHENSON, LA
   SCHNEIDER, JA
   WEISSENBACH, J
   POLYMEROPOULOS, MH
   TOWN, MM
   VANTHOFF, W
   FARRALL, M
   MATHEW, CG
AF MCDOWELL, GA
   GAHL, WA
   STEPHENSON, LA
   SCHNEIDER, JA
   WEISSENBACH, J
   POLYMEROPOULOS, MH
   TOWN, MM
   VANTHOFF, W
   FARRALL, M
   MATHEW, CG
TI LINKAGE OF THE GENE FOR CYSTINOSIS TO MARKERS ON THE SHORT ARM OF
   CHROMOSOME-17
SO NATURE GENETICS
LA English
DT Note
ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE; CHILDREN
C1 INST CHILD HLTH,LONDON WC1N 1EH,ENGLAND.
   WELLCOME TRUST CTR HUMAN GENET,NUFFIELD ORTHOPAED CTR,OXFORD OX3 7LD,ENGLAND.
   NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892.
   UNIV CALIF SAN DIEGO,SCH MED,DEPT PEDIAT,LA JOLLA,CA 92093.
   GENETHON,HUMAN GENOME RES CTR,F-91002 EVRY,FRANCE.
   NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892.
RP MCDOWELL, GA (reprint author), UNITED MED & DENT SCH,GUYS HOSP,DIV MED & MOLEC GENET,LONDON SE1 9RT,ENGLAND.
OI Beckmann, Jacques S /0000-0002-9741-1900
NR 14
TC 57
Z9 58
U1 0
U2 0
PU NATURE PUBLISHING CO
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 1995
VL 10
IS 2
BP 246
EP 248
DI 10.1038/ng0695-246
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA RA857
UT WOS:A1995RA85700028
ER

PT J
AU SPIEGEL, AM
AF SPIEGEL, AM
TI G-PROTEIN GENE KNOCKOUT HITS THE GUT
SO NATURE MEDICINE
LA English
DT Editorial Material
ID MUTATIONS
RP SPIEGEL, AM (reprint author), NIDDKD,BETHESDA,MD 20892, USA.
NR 17
TC 7
Z9 7
U1 0
U2 0
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 JUN
PY 1995
VL 1
IS 6
BP 522
EP 524
DI 10.1038/nm0695-522
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA RN101
UT WOS:A1995RN10100032
PM 7585115
ER

PT J
AU NESTEROVA, M
   CHOCHUNG, YS
AF NESTEROVA, M
   CHOCHUNG, YS
TI A SINGLE-INJECTION PROTEIN-KINASE A-DIRECTED ANTISENSE TREATMENT TO
   INHIBIT TUMOR-GROWTH
SO NATURE MEDICINE
LA English
DT Article
ID I REGULATORY SUBUNIT; HL-60 LEUKEMIA-CELLS; AMINO-ACID SEQUENCE;
   RI-ALPHA-SUBUNIT; CATALYTIC SUBUNIT; MOLECULAR-CLONING; HUMAN TESTIS;
   MESSENGER-RNA; CANCER-CELLS; CAMP
AB Expression of the RI(alpha) subunit of cAMP-dependent protein kinase type I is enhanced in human cancer cell lines, in primary tumours, in cells after transformation and in cells upon stimulation of growth. We have investigated the effect of sequence-specific inhibition of RI(alpha) gene expression on in vivo tumour growth. We report that single injection RI(alpha) antisense treatment results in a reduction in RI(alpha) expression and inhibition of tumour growth. Tumour cells behaved like untransformed cells by making less protein kinase type I. The RI(alpha) antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to halt neoplastic growth in vivo.
C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892.
NR 31
TC 129
Z9 131
U1 1
U2 3
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 JUN
PY 1995
VL 1
IS 6
BP 528
EP 533
DI 10.1038/nm0695-528
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA RN101
UT WOS:A1995RN10100035
PM 7585118
ER

PT J
AU WLODAWER, A
   GUSTCHINA, A
   RESHETNIKOVA, L
   LUBKOWSKI, J
   ZDANOV, A
   HUI, KY
   ANGLETON, EL
   FARMERIE, WG
   GOODENOW, MM
   BHATT, D
   ZHANG, L
   DUNN, BM
AF WLODAWER, A
   GUSTCHINA, A
   RESHETNIKOVA, L
   LUBKOWSKI, J
   ZDANOV, A
   HUI, KY
   ANGLETON, EL
   FARMERIE, WG
   GOODENOW, MM
   BHATT, D
   ZHANG, L
   DUNN, BM
TI STRUCTURE OF AN INHIBITOR COMPLEX OF THE PROTEINASE FROM FELINE
   IMMUNODEFICIENCY VIRUS
SO NATURE STRUCTURAL BIOLOGY
LA English
DT Article
ID SYNTHETIC HIV-1 PROTEASE; CRYSTAL-STRUCTURE; TYPE-2 PROTEASE;
   IDENTIFICATION; RESOLUTION; REFINEMENT; SEQUENCE; SITES
AB The crystal structure of a recombinant form of the proteinase encoded by the feline immunodeficiency virus (FIV PR) has been solved at 2 Angstrom resolution and refined to an R-factor of 0.148. The refined structure includes a peptidomimetic, statine-based inhibitor, LP-149, which is an even more potent inhibitor of HIV PR. Kinetic parameters were obtained for the cleavage of five substrates by FIV PR, and inhibition constants were measured for four inhibitors. The structure of FIV PR resembles other related retroviral enzymes although few inhibitors of HIV PR are capable of inhibiting FIV PR. The structure of FIV PR will enhance our knowledge of this class of enzymes, and will direct testing of new proteinase inhibitors in a feline animal model.
C1 VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA.
   ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285.
   UNIV FLORIDA,DEPT BIOCHEM & MOLEC BIOL,GAINESVILLE,FL 32610.
   UNIV FLORIDA,DEPT PATHOL & EXPTL MED,GAINESVILLE,FL 32610.
RP WLODAWER, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702, USA.
NR 34
TC 58
Z9 59
U1 0
U2 0
PU NATURE PUBLISHING CO
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
SN 1072-8368
J9 NAT STRUCT BIOL
JI Nat. Struct. Biol.
PD JUN
PY 1995
VL 2
IS 6
BP 480
EP 488
DI 10.1038/nsb0695-480
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA RF668
UT WOS:A1995RF66800012
PM 7664111
ER

PT J
AU Loev, SJ
   Margolis, RL
   Young, WS
   Li, SH
   Schilling, G
   Ashworth, RG
   Ross, CA
AF Loev, SJ
   Margolis, RL
   Young, WS
   Li, SH
   Schilling, G
   Ashworth, RG
   Ross, CA
TI Cloning and expression of the rat atrophin-I (DRPLA disease gene)
   homologue
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE dentato-rubral and pallidoluysian atrophy; expansion mutation;
   glutamine; Huntington's disease; trinucleotide repeat; neurodegeneration
ID MOUSE ANDROGEN RECEPTOR; MOLECULAR-CLONING; MESSENGER-RNAS; PROTEIN;
   REPEAT
AB Dentatorubral pallidoluysian atrophy (DRPLA) is a rare, progressive, fatal neuropsychiatric disorder similar to Huntington's disease, caused by an expansion of a CAG trinucleotide repeat encoding glutamine. We have cloned the cDNA of the rat homologue of this gene. The cDNA contains a 3549 base pair open reading frame that is 88.2% identical to the human cDNA, with a predicted amino acid sequence that is 93.6% identical to the human sequence. The consecutive glutamine repeat is only five residues in length (normal. range in human: 7-35 glutamines) and is followed by a polymorphic region of alternating glutamine and proline residues (QQQQQPQPQPQPQQ) The sequence also includes a polymorphic proline repeat, a serine repeat, and a region of alternating acidic and basic residues. Northern analysis and in situ hybridization indicate that the gene is widely expressed as a 4.5 kb mRNA, with a neuronal distribution in the brain. The widespread expression of this gene is consistent with the possibility that DRPLA, like other glutamine repeat diseases, is a result of an abnormality at the protein level.
C1 JOHNS HOPKINS UNIV,SCH MED,MOLEC NEUROBIOL LAB,BALTIMORE,MD.
   JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD.
   JOHNS HOPKINS UNIV,SCH MED,DEPT MED GENET,BALTIMORE,MD.
   JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH MED,PROGRAM CELLULAR & MOLEC MED,BALTIMORE,MD 21205.
   NIMH,CELL BIOL LAB,BETHESDA,MD 20892.
RI Young, W Scott/A-9333-2009; Ross, Christopher/H-8395-2013
OI Young, W Scott/0000-0001-6614-5112; 
FU NIMH NIH HHS [MH50763, NIMHMH 15330-15]; NINDS NIH HHS [NS34172]
NR 48
TC 11
Z9 13
U1 0
U2 0
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JUN
PY 1995
VL 2
IS 3
BP 129
EP 138
DI 10.1006/nbdi.1995.0014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA UD913
UT WOS:A1995UD91300001
PM 9173996
ER

PT J
AU MORENS, DM
   GRANDINETTI, A
   REED, D
   WHITE, LR
   ROSS, GW
AF MORENS, DM
   GRANDINETTI, A
   REED, D
   WHITE, LR
   ROSS, GW
TI CIGARETTE-SMOKING AND PROTECTION FROM PARKINSONS-DISEASE - FALSE
   ASSOCIATION OR ETIOLOGIC CLUE
SO NEUROLOGY
LA English
DT Review
ID ENVIRONMENTAL RISK-FACTORS; DIAGNOSED ALZHEIMERS-DISEASE; MONOAMINE
   OXIDASE-B; ALCOHOL-CONSUMPTION; OLFACTORY FUNCTION; YOUNG-ONSET;
   NICOTINE; DOPAMINE; DEMENTIA; HYPOTHESIS
AB We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.
C1 UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822.
   EAST WEST CTR,HONOLULU,HI 96848.
   BUCK CTR RES AGING,NOVATA,CA.
   NIA,BETHESDA,MD 20892.
   NIA,HONOLULU ASIA AGING STUDY,HONOLULU,HI.
   US DEPT VET AFFAIRS,HONOLULU,HI.
RP MORENS, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH SCI,BIOMED D103,1960 E W RD,HONOLULU,HI 96822, USA.
FU NINDS NIH HHS [R01 NS 30371]
NR 107
TC 279
Z9 287
U1 0
U2 7
PU LITTLE BROWN CO
PI BOSTON
PA 34 BEACON STREET, BOSTON, MA 02108-1493
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN
PY 1995
VL 45
IS 6
BP 1041
EP 1051
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA RC993
UT WOS:A1995RC99300002
PM 7783862
ER

PT J
AU JOHANNES, CB
   LINET, MS
   STEWART, WF
   CELENTANO, DD
   LIPTON, RB
   SZKLO, M
AF JOHANNES, CB
   LINET, MS
   STEWART, WF
   CELENTANO, DD
   LIPTON, RB
   SZKLO, M
TI RELATIONSHIP OF HEADACHE TO PHASE OF THE MENSTRUAL-CYCLE AMONG
   YOUNG-WOMEN - A DAILY DIARY STUDY
SO NEUROLOGY
LA English
DT Article
ID LONGITUDINAL DATA-ANALYSIS; PERCUTANEOUS ESTRADIOL; MIGRAINE; AURA; AGE;
   PROGESTERONE; PREVALENCE; SCALE; MOOD
AB We investigated the relationship between headache occurrence and phase of the menstrual cycle in a 4-month daily diary study of 74 women, 22 to 29 years old, residing in Washington County, Maryland, We selected subjects from women reporting a history of migraine symptoms and at least two migraine headache attacks per month in a 1986 to 1987 population-based survey, Data collection was from March 1987 through April 1988. By using detailed headache symptom information collected daily, we classified headaches into four categories: migraine with aura, migraine without aura, tension-type, and all other headaches. Odds ratios were separately estimated for the individual headache types and all types combined during each of three phases of the menstrual cycle, Risk of migraine without aura was significantly elevated during the first 3 days of menstruation (odds ratio, 1.66; 95% confidence interval, 1.21 to 2.26), but headache risk was not significantly increased during the 2 days immediately preceding onset of menstruation or on the estimated day of ovulation (day 14 before the onset of menstruation). Participants reported headaches on 28% of the study days overall, suggesting that onset of menstruation is an independent but not exclusive precipitating factor for headache attacks among young adult women with migraine. Our data show that onset of menstruation only accounts for a small proportion of migraine attacks among young women with frequent episodes of migraine.
C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD.
   NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,BETHESDA,MD 20892.
   JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21205.
   ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10467.
   ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL,BRONX,NY 10467.
   ALBERT EINSTEIN COLL MED,DEPT SOCIAL MED,BRONX,NY 10467.
RP JOHANNES, CB (reprint author), NEW ENGLAND RES INST INC,9 GALEN ST,WATERTOWN,MA 02172, USA.
FU NINDS NIH HHS [NS 19381]
NR 40
TC 125
Z9 126
U1 0
U2 3
PU LITTLE BROWN CO
PI BOSTON
PA 34 BEACON STREET, BOSTON, MA 02108-1493
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN
PY 1995
VL 45
IS 6
BP 1076
EP 1082
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA RC993
UT WOS:A1995RC99300006
PM 7783866
ER

PT J
AU STONE, LA
   SMITH, ME
   ALBERT, PS
   BASH, CN
   MALONI, H
   FRANK, JA
   MCFARLAND, HF
AF STONE, LA
   SMITH, ME
   ALBERT, PS
   BASH, CN
   MALONI, H
   FRANK, JA
   MCFARLAND, HF
TI BLOOD-BRAIN-BARRIER DISRUPTION ON CONTRAST-ENHANCED MRI IN PATIENTS WITH
   MILD RELAPSING-REMITTING MULTIPLE-SCLEROSIS - RELATIONSHIP TO COURSE,
   GENDER, AND AGE
SO NEUROLOGY
LA English
DT Article
ID MAGNETIC-RESONANCE; DISEASE-ACTIVITY
AB MRI has provided insight into the pathophysiology and course of MS, particularly through the use of a paramagnetic contrast agent that allows visualization of blood-brain barrier (BBB) breakdown. Neither the overall frequency of BBB breakdown in MS patients nor the characteristics associated with BBB breakdown in MS are known. We studied 68 relapsing-remitting RIS (RRMS) patients with three monthly MRIs to examine these questions. Seventy-eight percent of the RRMS patients studied had evidence of BBB breakdown on at least one MRI. While there was a great deal of variability among patients in terms of mean enhancing lesion frequency, BBB breakdown was associated with younger age at onset of disease, measured by age at first symptom or age at diagnosis, and more severe disease as measured by Expanded Disability Status Scale scores equal to or greater than 4.0. We found no relationship between BBB breakdown and duration of disease or gender. We conclude that BBB breakdown is a relatively common phenomenon in RRMS patients and may be most commonly found in patients with more aggressive disease and younger onset. These findings have implications for clinical trials that use MRI as an outcome measure.
C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892.
   NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892.
RP STONE, LA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BLDG 10,RM 5B16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 16
TC 94
Z9 95
U1 0
U2 5
PU LITTLE BROWN CO
PI BOSTON
PA 34 BEACON STREET, BOSTON, MA 02108-1493
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN
PY 1995
VL 45
IS 6
BP 1122
EP 1126
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA RC993
UT WOS:A1995RC99300015
PM 7783875
ER

PT J
AU HYDE, TM
   STACEY, ME
   COPPOLA, R
   HANDEL, SF
   RICKLER, KC
   WEINBERGER, DR
AF HYDE, TM
   STACEY, ME
   COPPOLA, R
   HANDEL, SF
   RICKLER, KC
   WEINBERGER, DR
TI CEREBRAL MORPHOMETRIC ABNORMALITIES IN TOURETTES-SYNDROME - A
   QUANTITATIVE MRI STUDY OF MONOZYGOTIC TWINS
SO NEUROLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; MIDBRAIN INVOLVEMENT; BASAL GANGLIA;
   FOLLOW-UP; CHILDREN; VOLUMES
AB Although the pathologic substrate of Tourette's syndrome (TS) is unknown, studies have implicated subtle changes in the basal ganglia. To further investigate structural basal ganglia pathology in TS, we performed morphometric analyses of MRIs of 10 monozygotic twin pairs discordant for severity of TS but concordant for the presence of tic disorders (mean age, 16.3 years; range, 9 to 31 years). Right caudate volume was slightly but significantly reduced in the relatively more severely affected twins as a group compared with the less affected twins (mean difference = 6%, p < 0.01). Most of this difference was attributable to volume reduction in the anterior right caudate (p < 0.02), which was smaller in the more severely affected twin in nine of 10 twin sets. The mean volume of the left lateral ventricle was 16% smaller in the more severely affected twins than in the less severely affected twins (p < 0.01). The normal asymmetry of the lateral ventricles (left greater than right) was not present in the more severely affected twins, who had a trend toward a larger right lateral ventricle. Moreover, the difference within a pair in the degree of loss of the normal ventricular asymmetry correlated with the difference within a pair in the severity of the tic disorder (r = 0.75, p < 0.02). There were no other basal ganglia, ventricular volumetric, or asymmetry abnormalities. These findings partially replicate other MRI studies and suggest that subtle structural abnormalities in the CNS, particularly in the caudate, may play a role in the pathophysiology of TS. Because monozygotic twins are genetically identical, these structural abnormalities must reflect adverse environmental events.
RP HYDE, TM (reprint author), NIMH,ST ELIZABETHS HOSP,NEUROSCI RES CTR,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA.
NR 34
TC 141
Z9 144
U1 0
U2 1
PU LITTLE BROWN CO
PI BOSTON
PA 34 BEACON STREET, BOSTON, MA 02108-1493
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN
PY 1995
VL 45
IS 6
BP 1176
EP 1182
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA RC993
UT WOS:A1995RC99300025
PM 7783885
ER

PT J
AU WONG, PC
   PARDO, CA
   BORCHELT, DR
   LEE, MK
   COPELAND, NG
   JENKINS, NA
   SISODIA, SS
   CLEVELAND, DW
   PRICE, DL
AF WONG, PC
   PARDO, CA
   BORCHELT, DR
   LEE, MK
   COPELAND, NG
   JENKINS, NA
   SISODIA, SS
   CLEVELAND, DW
   PRICE, DL
TI AN ADVERSE PROPERTY OF A FAMILIAL ALS-LINKED SOD1 MUTATION CAUSES
   MOTOR-NEURON DISEASE CHARACTERIZED BY VACUOLAR DEGENERATION OF
   MITOCHONDRIA
SO NEURON
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN-SUPEROXIDE-DISMUTASE; TRANSGENIC
   MICE; OXIDATIVE DAMAGE; MODEL; GENE
AB Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease. At lower levels of mutant accumulation, pathology is restricted to lower motor neurons, whereas higher levels cause more severe abnormalities and affect a variety of other neuronal populations. The most obvious cellular abnormality is the presence in axons and dendrites of membrane-bounded vacuoles, which appear to be derived from degenerating mitochondria. Since multiple lines of mice expressing wild-type human SOD1 at similar and higher levels do not show disease, the disease in mice expressing the G37R mutant SOD1 must arise from the acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity.
C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205.
   NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21701.
   UNIV CALIF SAN DIEGO,LUDWIG INST CANC RES,DEPT MED,LA JOLLA,CA 92093.
   UNIV CALIF SAN DIEGO,LUDWIG INST CANC RES,RES DEPT,LA JOLLA,CA 92093.
RP WONG, PC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205, USA.
RI Lee, Michael/D-9491-2013
OI Lee, Michael/0000-0001-5865-9682
FU NCI NIH HHS [N01 CO 4600]; NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS
   20471]
NR 43
TC 1047
Z9 1059
U1 6
U2 46
PU CELL PRESS
PI CAMBRIDGE
PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138
SN 0896-6273
J9 NEURON
JI Neuron
PD JUN
PY 1995
VL 14
IS 6
BP 1105
EP 1116
DI 10.1016/0896-6273(95)90259-7
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA RF987
UT WOS:A1995RF98700003
PM 7605627
ER

PT J
AU KEEFE, KA
   GERFEN, CR
AF KEEFE, KA
   GERFEN, CR
TI D1-D2 DOPAMINE-RECEPTOR SYNERGY IN STRIATUM - EFFECTS OF INTRASTRIATAL
   INFUSIONS OF DOPAMINE AGONISTS AND ANTAGONISTS ON IMMEDIATE-EARLY
   GENE-EXPRESSION
SO NEUROSCIENCE
LA English
DT Article
ID C-FOS EXPRESSION; TERM SYNAPTIC DEPRESSION; HEMI-PARKINSONIAN RAT;
   SUBSTANTIA-NIGRA; STRIATOPALLIDAL NEURONS; D1; ENKEPHALIN; STIMULATION;
   DYNORPHIN; ACTIVATION
AB Manipulations of D1- or D2-dopamine receptors have differential and selective effects on the striatonigral and striatopallidal output pathways of the striatum, respectively. However, combined stimulation of these receptors produces synergistic responses. To examine the locus of this interaction in vivo, we infused D1- or D2-receptor agents into the striatum of freely moving, dopamine-depleted rats given systemic injections of the D1 agonist SKF 38393 and the D2 agonist quinpirole. Expression of the immediate early genes zif268 and c-fos, as determined by in situ hybridization histochemistry, was used as a measure of changes in the function of striatal neurons. Systemic administration of SKF 38393 produced a dose-dependent increase in the expression of immediate early genes in the dopamine-depleted striatum. Quinpirole, on the other hand, decreased the basal expression of zif268 in both the lesioned and intact striatum. However, combined administration of quinpirole with SKF 38393 significantly enhanced immediate early gene expression in the dopamine-depleted striatum relative to that seen with SKF 38393 alone. Intrastriatal infusion of SKF 38393 produced a concentration-dependent increase in immediate early gene expression in the striatum. Furthermore, intrastriatal application of the D1-receptor antagonist SCH 23390 blocked the induction of immediate early genes by SKF 38393 given systemically either alone or with quinpirole. The induction of immediate early genes by co-administration of SKF 38393 and quinpirole was also significantly attenuated by intrastriatal administration of the D2-receptor antagonist eticlopride.
   These data show that D1-D2 synergy is operative in the dopamine-depleted striatum, is reflected in increases in the expression of the immediate early genes zif268 and c-fos, and is a consequence of activation of both D1 and D2 receptors within the striatum rather than in extrastriatal sites. The data further suggest that the enhanced induction of immediate early genes in the dopamine-depleted striatum of rats receiving SKF 38393 with quinpirole reflects a D2-mediated potentiation of a D1-dependent process.
C1 NIMH,SYST NEUROSCI LAB,NEUROANAT SECT,BETHESDA,MD 20892.
NR 44
TC 108
Z9 110
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUN
PY 1995
VL 66
IS 4
BP 903
EP 913
DI 10.1016/0306-4522(95)00024-D
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA RA258
UT WOS:A1995RA25800012
PM 7651617
ER

PT J
AU HUANG, Y
   SAVORY, J
   HERMAN, MM
   NICHOLSON, JR
   REYES, MR
   BOYD, JC
   WILLS, MR
AF HUANG, Y
   SAVORY, J
   HERMAN, MM
   NICHOLSON, JR
   REYES, MR
   BOYD, JC
   WILLS, MR
TI QUANTITATIVE-EVALUATION OF AL MALTOLATE-INDUCED NEURODEGENERATION WITH
   SUBSEQUENT AL REMOVAL BY DESFERRIOXAMINE TREATMENT
SO NEUROTOXICOLOGY
LA English
DT Article
DE ALUMINUM REMOVAL; DESFERRIOXAMINE; INTRACISTERNAL AL; QUANTITATION
ID ALZHEIMERS-DISEASE; ALUMINUM MALTOL; RABBITS
AB The intracisternal administration of aluminum maltolate to New Zealand white rabbits produces a reproducible neurofibrillary degeneration which is significantly reversed by desferrioxamine treatment. Quantitative analysis of brain and spinal cord tissue demonstrates that the aluminum deposition is higher close to the injection site than at locations further removed from the point of administration. Most importantly, treatment with desferrioxamine removes most of the aluminum from the brain and spinal cord, even from the sites of highest concentration. The ability to manipulate this system in the formation and degradation of NFD and in removal of aluminum may shed light on mechanisms of NFD formation and have implications for therapeutic advances in the treatment of certain human neurodegenerative diseases. (C) 1995 Intox Press, Inc.
C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908.
   UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908.
   NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032.
NR 8
TC 11
Z9 11
U1 1
U2 2
PU INTOX PRESS INC
PI LITTLE ROCK
PA PO BOX 24865, LITTLE ROCK, AR 72221
SN 0161-813X
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD SUM
PY 1995
VL 16
IS 2
BP 291
EP 296
PG 6
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA RF398
UT WOS:A1995RF39800009
PM 7566688
ER

PT J
AU HICKEY, CA
   CLIVER, SP
   MCNEAL, SF
   HOFFMAN, HJ
   GOLDENBERG, RL
AF HICKEY, CA
   CLIVER, SP
   MCNEAL, SF
   HOFFMAN, HJ
   GOLDENBERG, RL
TI PRENATAL WEIGHT-GAIN PATTERNS AND SPONTANEOUS PRETERM BIRTH AMONG
   NONOBESE BLACK-AND-WHITE WOMEN
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID GROWTH-RETARDATION; GESTATIONAL-AGE; FETAL GROWTH; RISK-FACTORS;
   DELIVERY; PREGNANCY
AB Objective: To examine the relationship between prenatal weight gain and spontaneous preterm delivery, using the Institute of Medicine (IOM) guidelines.
   Methods: Nonobese low-income black (677 subjects) and white (338) women were grouped by ethnicity and prepregnancy body mass index (BMI) as low (less than 19.8) or normal (19.8-26.0). The relationship of total gain (first trimester) and weekly rate of gain (second and third trimester) to spontaneous preterm delivery was determined while controlling for sociodemographic and reproductive variables as well as for time between last weight observation and delivery.
   Results: For all women combined, the mean (+/- standard deviation) weight gain during the first trimester was 2.48 +/- 3.36 kg, and the mean rate of gain during the second and third trimesters was 0.49 +/- 0.21 and 0.45 +/- 0.28 kg/week, respectively. Low first- or second-trimester weight gain was not associated with increased adjusted odds ratios (OR) for spontaneous preterm delivery. Third-trimester rates of gain below the lower limit of the IOM-recommended range (less than 0.38 kg/week with low BMI, less than 0.37 kg/week with normal BMI) were associated with increased preterm delivery among all women (OR 2.46, 95% confidence interval [CI] 1.53-3.92), all black women (OR 1.98, 95% CI 1.16-3.41), and all white women (OR 4.05, 95% CI 1.41-11.66).
   Conclusion: These observations suggest that a low third-trimester rate of weight gain, defined using IOM guidelines, is associated with an increased risk of spontaneous preterm delivery among nonobese black and white women.
C1 UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,CTR OBSTET RES,BIRMINGHAM,AL 35294.
   NIDOCD,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD.
RP HICKEY, CA (reprint author), UNIV ALABAMA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BIRMINGHAM,AL 35294, USA.
FU NICHD NIH HHS [1-HD-4-2811]; PHS HHS [282-92-0055, MCJ-9040]
NR 24
TC 50
Z9 53
U1 1
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 JUN
PY 1995
VL 85
IS 6
BP 909
EP 914
DI 10.1016/0029-7844(95)00067-2
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA QZ918
UT WOS:A1995QZ91800001
PM 7770259
ER

PT J
AU FORRESTER, K
   LUPOLD, SE
   OTT, VL
   CHAY, CH
   BAND, V
   WANG, XW
   HARRIS, CC
AF FORRESTER, K
   LUPOLD, SE
   OTT, VL
   CHAY, CH
   BAND, V
   WANG, XW
   HARRIS, CC
TI EFFECTS OF P53 MUTANTS ON WILD-TYPE P53-MEDIATED TRANSACTIVATION ARE
   CELL-TYPE DEPENDENT
SO ONCOGENE
LA English
DT Article
DE P53; P53 MUTANTS; TRANSACTIVATION; CELL TYPE SPECIFICITY
ID TRANSCRIPTIONAL ACTIVITY; GENE AMPLIFICATION; PROTEIN COMPLEXES; RAS
   MUTATIONS; CYCLE CONTROL; BINDING-SITE; DNA-DAMAGE; LINES; CANCER;
   EXPRESSION
AB The spectrum of p53 mutations differs among human cancer types. We have hypothesized that the p53 mutational spectrum observed in particular tumor types reflects the functional ability of different p53 mutants to modulate wild-type (WT) p53-dependent gene transcription. Missense p53 mutants representing several mutational hotspot codons were cotransfected with WT p53 and analysed for their effects on p53-dependent transactivation of a reporter construct containing a specific p53 binding sequence (PG(13)-CAT) in human tumor cell lines lacking endogenous p53. Our results show that the ability of p53 mutants to inhibit WT p53-mediated transactivation is cell type dependent. In cell lines derived from a lung adenocarcinoma and mesothelioma, the transactivation function of WT p53 was strongly inhibited by all p53 mutants examined. However, in cell lines derived from a prostate carcinoma and an osteosarcoma, the mutants examined generally had only minimal dominant negative effects. In cell lines derived from a hepatocellular carcinoma and an ovarian carcinoma, two mutants (248(trp) and 273(his)) enhanced WT p53 mediated-transactivation of the reporter construct. Additional mutants retained the ability to inhibit WT p53-mediated transactivation in these cell lines. In addition, in a series of four breast tumor cell lines, the p53 mutants examined had similar effects on WT p53 transactivation ability including enhanced transactivation activity in the 273(his) cotransfectants. The p53 mutants were incapable of transactivating the PG(13)-CAT reporter in the absence of WT p53 expression. Therefore, the dominant negative effects of p53 mutants on WT p53 function may vary depending on the particular cell type. In addition, mutants with stronger inhibitory capabilities may confer a selective advantage during the tumorigenic process.
C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892.
   TUFTS UNIV NEW ENGLAND MED CTR,DEPT RADIOL ONCOL & BIOCHEM,BOSTON,MA 02111.
RI Wang, Xin/B-6162-2009
NR 69
TC 103
Z9 103
U1 0
U2 1
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 1
PY 1995
VL 10
IS 11
BP 2103
EP 2111
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA RB703
UT WOS:A1995RB70300005
PM 7784055
ER

PT J
AU SU, LC
   MUKHERJEE, AB
   MUKHERJEE, BB
AF SU, LC
   MUKHERJEE, AB
   MUKHERJEE, BB
TI EXPRESSION OF ANTISENSE OSTEOPONTIN RNA INHIBITS TUMOR PROMOTER-INDUCED
   NEOPLASTIC TRANSFORMATION OF MOUSE JB6 EPIDERMAL-CELLS
SO ONCOGENE
LA English
DT Article
DE OSTEOPONTIN; ANTISENSE OPN; TUMOR PROMOTION
ID RAT-KIDNEY CELLS; SECRETED PHOSPHOPROTEIN; BONE SIALOPROTEIN;
   MESSENGER-RNA; PHYSIOLOGICAL-PROPERTIES; NONPHOSPHORYLATED FORMS;
   BINDING-PROPERTIES; MAMMALIAN-CELLS; PROTEINS; TUMORIGENICITY
AB Elevated expression of osteopontin (OPN), a secreted adhesive phosphoglycoprotein, is frequently associated with many transformed cell lines of epithelial and stromal origin. Moreover, several clonal lines of preneoplastic JB6 cells derived from Balb/c mouse epidermal cultures (Colburn et al., 1978, 1979), upon treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), become irreversibly oncogenic and concomitantly synthesize OPN at elevated levels (Smith and Denhardt, 1989). In the present study we sought to determine whether OPN expression facilitates transformation of such preneoplastic (initiated) cells. We transfected TPA-promotable JB6 c141.5a cells with an expression vector containing mouse OPN cDNA in antisense orientation under transcriptional control of dexamethasone-inducible MMTV-LTR promoter. Four stably transfected clones, which expressed drastically reduced levels of OPN in the presence of both dexamethasone and TPA, were characterized. We found that (a) more than 20 copies of OPN antisense cDNA were stably incorporated into the genome of cells from two of these clones that were examined by Southern blot analysis; (b) dexamethasone-induced expression of antisense OPN RNA prevented augmented OPN expression at both mRNA and protein levels following TPA treatment; and (c) cells from all four clones failed to form colonies in soft agar medium containing both dexamethasone and TPA. Taken together, these data demonstrate that inhibition of elevated OPN expression blocks TPA-induced anchorage-independent growth of JB6 c141.5a cells, suggesting the possibility that OPN overproduction is causally related to transformation of preneoplastic cells.
C1 MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3A 1B1,CANADA.
   MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3A 1B1,CANADA.
   NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892.
NR 39
TC 42
Z9 42
U1 0
U2 0
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 1
PY 1995
VL 10
IS 11
BP 2163
EP 2169
PG 7
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA RB703
UT WOS:A1995RB70300011
PM 7784060
ER

PT J
AU KUZMIN, I
   DUH, FM
   LATIF, F
   GEIL, L
   ZBAR, B
   LERMAN, MI
AF KUZMIN, I
   DUH, FM
   LATIF, F
   GEIL, L
   ZBAR, B
   LERMAN, MI
TI IDENTIFICATION OF THE PROMOTER OF THE HUMAN VON HIPPEL-LINDAU DISEASE
   TUMOR-SUPPRESSOR GENE
SO ONCOGENE
LA English
DT Article
DE VON HIPPEL-LINDAU DISEASE; PROMOTER; TUMOR SUPPRESSOR
ID HUMAN RETINOBLASTOMA GENE; TRANSCRIPTION FACTOR; SMALL REGION;
   CHROMOSOME-3; CARCINOMA; NRF-1; LOCUS; DNA
AB The von Hippel-Lindau (VHL) disease gene is a novel multiple tumor suppressor gene which plays a causal role in the origin of some common cancers including clear cell renal carcinomas and hemangioblastomas of the central nervous system. Here we report the identification of transcription start sites and the promoter of the human VHL gene. The promoter sequence does not contain TATA and CCAAT boxes. Transcription is initiated around a putative SP1 binding site about 60 bp upstream from the first AUG codon in the VHL mRNA. Several putative transcription factor binding sites, notably for nuclear respiratory factor 1 and PAX, were found upstream of the transcription start sites, Promoter-luciferase expression constructs demonstrate, that the promoter is functional when transfected into 293 cells (transformed primary human embryonal kidney cells) and UMRC 6 renal carcinoma cells. Activity is dependent on correct orientation of the promoter. A minimal promoter region of 106 bp was delineated, A set of VHL minigenes, containing the 5' flanking VHL genomic region, was constructed and transfected into UMRC 6 cells. In these cells the level of transcription from the minigenes driven by VHL promoter was comparable with endogenous VHL expression.
C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
RP KUZMIN, I (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702, USA.
NR 43
TC 64
Z9 66
U1 5
U2 14
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 1
PY 1995
VL 10
IS 11
BP 2185
EP 2194
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA RB703
UT WOS:A1995RB70300014
PM 7784063
ER

PT J
AU BIESECKER, LG
   GIANNOLA, DM
   EMERSON, SG
AF BIESECKER, LG
   GIANNOLA, DM
   EMERSON, SG
TI IDENTIFICATION OF ALTERNATIVE EXONS, INCLUDING A NOVEL EXON, IN THE
   TYROSINE KINASE RECEPTOR GENE ETK2/TYRO3 THAT EXPLAIN DIFFERENCES IN 5'
   CDNA SEQUENCES
SO ONCOGENE
LA English
DT Note
DE RECEPTOR; PROTEIN TYROSINE KINASE; BRAIN
ID CELLS
AB Protein tyrosine kinase transmembrane receptors trigger signal transduction cascades upon ligand binding, resulting in cellular proliferation, differentiation, differentiation inhibition or apoptosis depending upon the cell target. The ETK2/TYRO3 receptor is a tyrosine kinase expressed in embryonic stem cells, brain and testis that has recently been cloned by several groups. Analysis of cDNA clones isolated from several tissues shows 2 isoforms of the Etk2/tyro3 gene product that result from usage of alternative exons near the 5' end of the gene. In addition, our data suggest that a third alternative exon is positioned between these two alternative exons. This novel exon encodes yet another isoform that predicts a unique amino-terminal protein sequence, The alternative exons (exons 2A, 2B and 2C), predict three isoforms with different initiation codons, signal sequences and lengths. The existence of these multiple isoforms may be important for protein processing, translocation, or function.
C1 UNIV PENN,DEPT INTERNAL MED,DIV HEMATOL & ONCOL,PHILADELPHIA,PA 19104.
RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892, USA.
FU NCRR NIH HHS [M01RR00042]; NICHD NIH HHS [HD28820]; NIDDK NIH HHS
   [DK08414]
NR 17
TC 13
Z9 14
U1 0
U2 0
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 1
PY 1995
VL 10
IS 11
BP 2239
EP 2242
PG 4
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA RB703
UT WOS:A1995RB70300020
PM 7784069
ER

PT J
AU VELASCO, JA
   RAMSAMOOJ, P
   THRAVES, PJ
   EVA, A
   DRITSCHILO, A
   NOTARIO, V
AF VELASCO, JA
   RAMSAMOOJ, P
   THRAVES, PJ
   EVA, A
   DRITSCHILO, A
   NOTARIO, V
TI COREGULATED EXPRESSION OF DBL AND POLY(ADP-RIBOSE) POLYMERASE IN
   EWINGS-SARCOMA CELLS AND DBL-TRANSFORMED NIH3T3 FIBROBLASTS
SO ONCOGENE
LA English
DT Note
DE EWINGS SARCOMA; GENE EXPRESSION; DBL ONCOGENE; POLY(ADP-RIBOSE)
   POLYMERASE; NIH3T3 FIBROBLASTS
ID PROTO-ONCOGENE; DNA; PROTOONCOGENE; CLONING; PRODUCT; ORIGIN; CDNA; GENE
AB Poly(ADP-ribose) polymerase (PADPRP) is a ubiquitous enzyme constitutively expressed at low levels in the majority of eukaryotic cells, including most mammalian tumors and tumor-derived cell lines. Overexpression of PADPRP following the introduction of cDNA recombinant constructs into various cell types results in cell death. An exception to this effect are Ewing's sarcoma (ES) cells, which have been shown to contain elevated steady-state levels of PADPRP mRNA and high constitutive levels of protein and polymerase activity. In fact, this excess of PADPRP has been suggested to participate in the intrinsic radiosensitivity of Ewing's sarcomas, a highly malignant childhood bone tumor frequently curable with radiotherapy. It appears that ES cells might possess a hitherto unknown mechanism(s) by which PADPRP overexpression is controlled and made compatible with cell survival and proliferation.
   In order to investigate the contribution of other genetic alterations to PADPRP regulation in ES cells, we analysed the expression levels of PADPRP and of other genes, such as oncogenes and tumor suppressor genes, which may enhance the proliferative potential of ES cells. We have detected a positive correlation between the expression levels of the DNA-repair enzyme poly(ADP-ribose) polymerase and the dbl proto-oncogene in Ewing's sarcoma cells. The co-regulated expression of these genes has been established in NIH3T3 cells transformed by the human dbl oncogene or by overexpression of the dbl proto-oncogene. In both instances, the increase in dbl expression resulted in elevated levels of PADPRP mRNA and polymerase activity. The dbl oncogene was more efficient than the proto-oncogene in upregulating PADPRP expression. The inability of other oncogenes to upregulate PADPRP upon transformation of NIH3T3 cells demonstrated the specificity of the dbl in the process. Transfection of dbl-transformed NIH3T3 cells with retroviral PADPRP vectors resulted in the establishment of clones with PADPRP levels higher than those detectable in untransformed NIH3T3 cells transfected with the same retroviral constructs. These results suggest that dbl plays a role in the mechanism by which mammalian cells autoregulate their endogenous levels of PADPRP. Post-translational modification of the dbl or proto-dbl proteins by cytoplasmic PADPRP does not participate in the mechanism(s) underlying the observed PADPRP/dbl co-regulation.
C1 GEORGETOWN UNIV,MED CTR,DEPT RADIAT MED,WASHINGTON,DC 20007.
   NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892.
RI Eva, Alessandra/J-8268-2016
OI Eva, Alessandra/0000-0003-2949-078X
FU NCI NIH HHS [R01-CA58986]
NR 25
TC 6
Z9 6
U1 0
U2 0
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 1
PY 1995
VL 10
IS 11
BP 2253
EP 2258
PG 6
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA RB703
UT WOS:A1995RB70300023
PM 7784072
ER

PT J
AU PANKAYATSELVAN, R
   GUZIEC, FS
   GOPALAN, AS
   RAGHAVACHARI, R
   GUZIEC, LJ
   WEI, DC
   FELSTED, RL
   GLOVER, CJ
AF PANKAYATSELVAN, R
   GUZIEC, FS
   GOPALAN, AS
   RAGHAVACHARI, R
   GUZIEC, LJ
   WEI, DC
   FELSTED, RL
   GLOVER, CJ
TI THE PREPARATION OF SOME ANALOGS OF MYRISTOYL COA
SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
LA English
DT Article
ID PROTEIN N-MYRISTOYLTRANSFERASE; ENZYME-CATALYZED REACTION;
   PALMITOYL-COENZYME-A; (METHYLENECYCLOPROPYL)ACETYL-COA; DEHYDROGENASE;
   INACTIVATION; INHIBITORS
C1 NCI,BIOL CHEM LAB,BETHESDA,MD 20892.
RP PANKAYATSELVAN, R (reprint author), NEW MEXICO STATE UNIV,DEPT CHEM,LAS CRUCES,NM 88003, USA.
NR 18
TC 2
Z9 2
U1 1
U2 1
PU ORGANIC PREP PROCEDURES INC
PI NEWTON HIGHLANDS
PA PO BOX 9, NEWTON HIGHLANDS, MA 02161
SN 0030-4948
J9 ORG PREP PROCED INT
JI Org. Prep. Proced. Int.
PD JUN
PY 1995
VL 27
IS 3
BP 347
EP 354
PG 8
WC Chemistry, Organic
SC Chemistry
GA RE546
UT WOS:A1995RE54600004
ER

PT J
AU KRIZMAN, DB
   HOFMANN, TA
   DESILVA, U
   GREEN, ED
   MELTZER, PS
   TRENT, JM
AF KRIZMAN, DB
   HOFMANN, TA
   DESILVA, U
   GREEN, ED
   MELTZER, PS
   TRENT, JM
TI IDENTIFICATION OF 3'-TERMINAL EXONS FROM YEAST ARTIFICIAL CHROMOSOMES
SO PCR-METHODS AND APPLICATIONS
LA English
DT Article
ID FIELD GEL-ELECTROPHORESIS; TRANSCRIBED SEQUENCES; DNA; SELECTION;
   INSERTS; LIBRARY
AB We report an extension of 3'-terminal exon trapping technology to the identification of transcribed sequences from yeast artificial chromesomes (YACs). A 350-kb YAC containing mouse genomic DNA was gel-purfied and used as the target DNA for the 3'-terminal exon trapping strategy. A novel direct ligation/transfection approach was employed to Increase the efficiency of trapping 3'-terminal exons from recombinant vector-derived chimeric mRNA. The resulting RT-PCR product war then used to generate a plasmid library. Randomly chosen individual subclones from this library were sequenced, and the results Indicate that 86% met sequence criteria characteristic of 3'-terminal exons, whereas 14% were background from identified sources. PCR mapping efforts suggest eight putative last exons present within this YAC, whereas RT-PCR studies demonstrate that three reside within valid expressed sequences.
C1 WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110.
RP KRIZMAN, DB (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892, USA.
FU NHGRI NIH HHS [P50-HG00201]
NR 18
TC 2
Z9 2
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS
PI PLAINVIEW
PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724
SN 1054-9803
J9 PCR METH APPL
JI PCR-Methods Appl.
PD JUN
PY 1995
VL 4
IS 6
BP 322
EP 326
PG 5
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA RM630
UT WOS:A1995RM63000002
PM 7580924
ER

PT J
AU CONNOR, EM
   MOFENSON, LM
AF CONNOR, EM
   MOFENSON, LM
TI ZIDOVUDINE FOR THE REDUCTION OF PERINATAL HUMAN-IMMUNODEFICIENCY-VIRUS
   TRANSMISSION - PEDIATRIC AIDS CLINICAL-TRIALS GROUP PROTOCOL-076 -
   RESULTS AND TREATMENT RECOMMENDATIONS
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE ZIDOVUDINE; HUMAN IMMUNODEFICIENCY VIRUS; PERINATAL TRANSMISSION
ID INFECTION; WOMEN; CARE
C1 NICHHD, CTR RES MOTHERS & CHILDRENS, PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH, BETHESDA, MD USA.
OI Mofenson, Lynne/0000-0002-2818-9808
NR 24
TC 38
Z9 39
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JUN
PY 1995
VL 14
IS 6
BP 536
EP 541
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA RC781
UT WOS:A1995RC78100012
PM 7667060
ER

PT J
AU GOLDIN, E
   BLANCHETTEMACKIE, EJ
   DWYER, NK
   PENTCHEV, PG
   BRADY, RO
AF GOLDIN, E
   BLANCHETTEMACKIE, EJ
   DWYER, NK
   PENTCHEV, PG
   BRADY, RO
TI CULTURED SKIN FIBROBLASTS DERIVED FROM PATIENTS WITH MUCOLIPIDOSIS-4 ARE
   AUTOFLUORESCENT
SO PEDIATRIC RESEARCH
LA English
DT Article
AB Mucolipidosis 4 (ML4) is an autosomal recessive disorder with both lipid and mucopolysaccharide storage. The disease is characterized by severe visual impairment and psychomotor retardation. In our effort to find a phenotypic marker for ML4 fibroblasts, living cells were stained with fluorescent compounds. The staining pattern in cells was complicated by auto-fluorescence. A careful study revealed that auto-fluorescence by itself was a sufficient marker for viable ML4 fibroblasts. ML4 cells in cultures obtained from four unrelated patients contain auto-fluorescent material. Auto-fluorescence was noted over a wide range of excitation wavelengths from similar to 365 to similar to 546 nn. The most intense fluorescence was observed in the lower wavelength range. Cultured fibroblasts from normal individuals or obligate ML4 heterozygotes did not fluoresce under adequately controlled culture conditions. High passage number or inadequate feeding caused a small proportion of fibroblasts obtained from normal individuals to auto-fluoresce. The auto-fluorescent material co-localized with phase-dense inclusion bodies, shown to be lysosomes by staining with LAMP-ab. These findings imply that fluorescence may relate to the specific compound(s) stored in the lysosomes. In a comparative study, neuronal ceroid lipofuscinosis fibroblasts were also fluorescent. Fibroblasts from other diseases such as Gaucher disease and glycogenosis type 2 did not show any fluorescence. These findings are currently used in our functional cloning strategy for determining the gene involved in ML4.
C1 NIDDKD,BETHESDA,MD 20892.
RP GOLDIN, E (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,ROOM 3D-04,BETHESDA,MD 20892, USA.
NR 13
TC 35
Z9 35
U1 0
U2 1
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD JUN
PY 1995
VL 37
IS 6
BP 687
EP 692
DI 10.1203/00006450-199506000-00003
PG 6
WC Pediatrics
SC Pediatrics
GA QZ552
UT WOS:A1995QZ55200003
PM 7651750
ER

PT J
AU ONO, S
   HATANAKA, T
   HOTTA, H
   TSUTSUI, M
   SATOH, T
   GONZALEZ, FJ
AF ONO, S
   HATANAKA, T
   HOTTA, H
   TSUTSUI, M
   SATOH, T
   GONZALEZ, FJ
TI CHLORZOXAZONE IS METABOLIZED BY HUMAN CYP1A2 AS WELL AS BY HUMAN CYP2E1
SO PHARMACOGENETICS
LA English
DT Article
DE CHLORZOXAZONE; CYTOCHROME P450; METABOLISM; ANILINE
ID HUMAN-LIVER; CYTOCHROME-P-450 ENZYMES; VACCINIA VIRUS; CDNA;
   HYDROXYLATION; EXPRESSION; SEQUENCE; IDENTIFICATION; TOLBUTAMIDE;
   DEMETHYLASE
AB Chlorzoxazone, a muscle-relaxing drug, is metabolized by carbon-hydroxylation at position 6, Chlorzoxazone has been suggested as an in vivo probe for CYP2E1, We studied the specificity of such a substrate using vaccinia virus expressed human P450 forms and the effect of inhibitors for chlorzoxazone metabolism by human liver microsomes, The 6-hydroxylation of chlorzoxazone was mediated by CYP1A2 as well as by CYP2E1, The K-m value of CYP1A2 and CYP2E1 for the reaction was 5.69 mu M and 232 mu M, respectively. However, the V-max value of CYP2E1 for the reaction was approximately 8.5-fold higher than that of CYP1A2. The CYP1A inhibitor, alpha-naphthoflavone, as well as the CYP2E1 inhibitor, diethyldithiocarbamate, decreased chlorzoxazone 6-hydroxylation at a low substrate concentration by human liver microsomes, Our results raise questions about the suitability of chlorzoxazone as an in vivo probe for hepatic CYP2E1 activity. In human liver microsomal samples, the K-m = 40 mu M was different from either the K-m of CYP1A2 or CYP2E1, We think that this discrepancy is due to the co-expression of similar levels of CYP1A2 and CYP2E1 in human liver, Furthermore, it is suggested that the role of CYP2E1 in 6-hydroxychlorzoxazone formation at the physiological chlorzoxazone concentration of 30-60 mu M is almost the same when compared to that of CYP1A2.
C1 CHIBA UNIV,FAC PHARMACEUT SCI,BIOCHEM PHARMACOL & BIOTOXICOL LAB,CHIBA 260,JAPAN.
   NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892.
RP ONO, S (reprint author), AMERSHAM KK,CENT LAB RES & DEV,2802-1 HIRATSUKA,SHIROI,CHIBA 27014,JAPAN.
NR 34
TC 108
Z9 109
U1 0
U2 6
PU CHAPMAN HALL LTD
PI LONDON
PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN
SN 0960-314X
J9 PHARMACOGENETICS
JI Pharmacogenetics
PD JUN
PY 1995
VL 5
IS 3
BP 143
EP 150
DI 10.1097/00008571-199506000-00002
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
   & Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
   & Pharmacy
GA RF435
UT WOS:A1995RF43500002
PM 7550365
ER

PT J
AU POPIK, P
   LAYER, RT
   SKOLNICK, P
AF POPIK, P
   LAYER, RT
   SKOLNICK, P
TI 100 YEARS OF IBOGAINE - NEUROCHEMICAL AND PHARMACOLOGICAL ACTIONS OF A
   PUTATIVE ANTI-ADDICTIVE DRUG
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID NALOXONE-PRECIPITATED WITHDRAWAL; NMDA RECEPTOR ANTAGONISTS;
   DIHYDROPYRIDINE BINDING-SITES; INDUCED LOCOMOTOR STIMULATION;
   MORPHINE-DEPENDENT MICE; EXCITATORY AMINO-ACIDS; INVIVO MICRODIALYSIS;
   PARASAGITTAL ZONES; OPIATE-WITHDRAWAL; DOPAMINE RELEASE
RP POPIK, P (reprint author), NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA.
RI Popik, Piotr/R-5383-2016
OI Popik, Piotr/0000-0003-0722-1263
NR 216
TC 111
Z9 111
U1 1
U2 9
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD JUN
PY 1995
VL 47
IS 2
BP 235
EP 253
PG 19
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RG231
UT WOS:A1995RG23100002
PM 7568327
ER

PT J
AU PENNYPACKER, KR
AF PENNYPACKER, KR
TI PHARMACOLOGICAL REGULATION OF TRANSCRIPTION FACTOR-BINDING
SO PHARMACOLOGY
LA English
DT Review
DE GENE REGULATION; DNA-BINDING ACTIVITY; PHOSPHORYLATION DEPHOSPHORYLATION
ID NF-KAPPA-B; ACTIVATED T-CELLS; PROTEIN-KINASE-C; JUN DNA-BINDING;
   GLYCOGEN-SYNTHASE KINASE-3; CAMP-RESPONSE-ELEMENT; LOOP-HELIX PROTEINS;
   GROWTH-HORMONE GENE; GLUCOCORTICOID RECEPTOR; NUCLEAR FACTOR
AB Organisms respond to extracellular stimuli by changing the expression of genes. Stimulation of the cell often induces a cascade of intracellular events that leads to activation of transcription factor DNA-binding complexes which modulate the transcription rate. Many cellular processes including development of the organism are dependent on these proteins to maintain proper levels of mRNA. A diversity of mechanisms has evolved to coordinate transcription factor binding to the specific DNA element which affects mRNA synthesis. Precise regulatory processes are present at the level of transcription, translation and posttranslation. Often, posttranslational processes alter affinities of factors to DNA-binding sites. In this review, the molecular controls of transcription factor binding to DNA will be examined, with specific examples of the pharmacologic regulation of transcription factor binding to DNA.
C1 NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709.
RI Pennypacker, Keith/I-5092-2012
NR 125
TC 8
Z9 8
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0031-7012
J9 PHARMACOLOGY
JI Pharmacology
PD JUN
PY 1995
VL 51
IS 1
BP 1
EP 12
DI 10.1159/000139311
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RF444
UT WOS:A1995RF44400001
PM 7568339
ER

PT J
AU COLOMBO, G
   AGABIO, R
   LOBINA, C
   REALI, R
   ZOCCHI, A
   FADDA, F
   GESSA, GL
AF COLOMBO, G
   AGABIO, R
   LOBINA, C
   REALI, R
   ZOCCHI, A
   FADDA, F
   GESSA, GL
TI SARDINIAN ALCOHOL-PREFERRING RATS - A GENETIC ANIMAL-MODEL OF ANXIETY
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE ALCOHOL-PREFERRING SP RATS; ALCOHOL-NONPREFERRING SNP RATS; VOLUNTARY
   ETHANOL INTAKE; ANXIETY; ELEVATED PLUS MAZE
ID ELEVATED PLUS-MAZE; ETHANOL; TESTS; BEHAVIOR; DRUGS; MOUSE
AB The present study was designed to assess the anxiety profile of the selectively bred alcohol-preferring sP and alcohol-nonpreferring sNP rats. Rats were offered either water (ethanol-naive rats) or a free choice of 10% (v/v) ethanol and water (ethanol-experienced rats) for 14 consecutive days prior to the test. Spontaneous exploration of an elevated plus maze was used as a behavioral measure of anxiety. Ethanol-naive sP rats spent less time in and made fewer entries into the open arms of the maze than ethanol-naive sNP rats. These results suggest a higher innate degree of anxiety in sP than in sNP rats. Moreover, time spent in and number of entries into the open arms of the maze were higher in ethanol-experienced than in ethanol-naive sP rats. This finding suggests that ethanol consumed voluntarily produces anxiolytic effects in sP rats. The results of the present study are discussed in terms of (a) anxiety as a genetic trait related to ethanol-preference in sP rats and (b) self-medication of anxiety as a possible factor promoting voluntary ethanol consumption in sP rats.
C1 UNIV CAGLIARI,INST HUMAN PHYSIOL,I-09124 CAGLIARI,ITALY.
   NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
RP COLOMBO, G (reprint author), UNIV CAGLIARI,BERNARD B BRODIE DEPT NEUROSCI,VIA PORCELL 4,I-09124 CAGLIARI,ITALY.
NR 25
TC 139
Z9 141
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD JUN
PY 1995
VL 57
IS 6
BP 1181
EP 1185
DI 10.1016/0031-9384(94)00382-F
PG 5
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA QY764
UT WOS:A1995QY76400025
PM 7652041
ER

PT J
AU PROTA, G
   LAMOREUX, ML
   MULLER, J
   KOBAYASHI, T
   NAPOLITANO, A
   VINCENSI, MR
   SAKAI, C
   HEARING, VJ
AF PROTA, G
   LAMOREUX, ML
   MULLER, J
   KOBAYASHI, T
   NAPOLITANO, A
   VINCENSI, MR
   SAKAI, C
   HEARING, VJ
TI COMPARATIVE-ANALYSIS OF MELANINS AND MELANOSOMES PRODUCED BY VARIOUS
   COAT COLOR MUTANTS
SO PIGMENT CELL RESEARCH
LA English
DT Article
DE PIGMENTATION; MELANIN; MELANOSOMES; MELANOGENESIS
ID TYROSINASE-RELATED PROTEIN; DOPACHROME CONVERSION; YELLOW MICE; AGOUTI
   GENE; MOUSE; LOCUS; HAIR; MELANOGENESIS; PIGMENTATION; EXPRESSION
AB Pigmentation in the skin, hair, and eyes of animals is influenced by a number of genes that modulate the activity of melanocytes, the intervention of enzymatic controls at different stages of the melanogenic process, and the physico-chemical properties of the final pigment. The results of combined phenotypic, ultrastructural, biochemical, and chemical analyses of hairs of a variety of defined genotypes on a common genetic background performed in this study are consistent with the view that pigmentation of dark to black hairs results from the incorporation of eumelanin pigments whereas that of yellow hairs results from the incorporation of eu- and pheomelanins. It is also clear that relatively minor differences in melanin content can have dramatic effects on visible hair color. A good correlation was found for expression of (and enzyme activities associated with) TRP1 and TRP2 with eumelanin synthesis and eumelanosome production.
C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892.
   UNIV NAPLES,DEPT ORGAN & BIOL CHEM,I-80134 NAPLES,ITALY.
   TEXAS A&M UNIV,TEXAS VET MED CTR,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843.
   US FDA,DIV VIROL,BETHESDA,MD 20892.
RI Napolitano, Alessandra /E-9761-2011
NR 51
TC 60
Z9 61
U1 1
U2 3
PU MUNKSGAARD INT PUBL LTD
PI COPENHAGEN
PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK
SN 0893-5785
J9 PIGM CELL RES
JI Pigm. Cell. Res.
PD JUN
PY 1995
VL 8
IS 3
BP 153
EP 163
DI 10.1111/j.1600-0749.1995.tb00657.x
PG 11
WC Cell Biology; Dermatology
SC Cell Biology; Dermatology
GA RM035
UT WOS:A1995RM03500006
PM 7567792
ER

PT J
AU SWANSON, DA
   TAYMAN, J
AF SWANSON, DA
   TAYMAN, J
TI BETWEEN A ROCK AND A HARD PLACE - THE EVALUATION OF DEMOGRAPHIC
   FORECASTS
SO POPULATION RESEARCH AND POLICY REVIEW
LA English
DT Article; Proceedings Paper
CT 14th International Symposium on Forecasting
CY JUN 12-15, 1994
CL STOCKHOLM, SWEDEN
SP Int Inst Forecasters
DE COGNITIVE DISSONANCE; PROPORTIONATE-REDUCTION-IN-ERROR; UTILITY
ID POPULATION PROJECTIONS; ACCURACY; BIAS
AB Forecasting, in general, has been described as an unavoidable yet impossible task. This irony, which comprises the 'rock' and the 'hard place' in the title, creates a high level of cognitive dissonance, which, in turn, generates stress for those both making and using forecasts that have non-trivial impacts. Why? Because the forecasted numbers that are invariably accorded a high degree of precision inexorably reveal their inevitable imprecision when the numbers forming the actuality finally take place and the numbers comprising the forecast's errors are precisely measured. The current state of the art in demography for dealing with the 'rock' and the 'hard place' is a less-than-successful strategy because it is based on an acceptance of accuracy as the primary evaluation criterion, which is the source of cognitive dissonance. One way to reduce cognitive dissonance is to change the relationship of the very cognitive elements creating it. We argue that forecast evaluations currently focused on accuracy and based on measures like RMSE and MAPE be refocused to include utility and propose for this purpose the 'Proportionate Reduction in Error' (PRE) measure. We illustrate our proposal with examples and discuss its advantages. We conclude that including PRE as an evaluation criterion can reduce stress by reducing cognitive dissonance without, at the same time, either trivializing the evaluation process or substantively altering how forecasts are done and presented.
C1 UNIV ARKANSAS MED SCI HOSP,NIMH,CTR RURAL MENTAL HEALTHCARE RES,LITTLE ROCK,AR 72205.
   SAN DIEGO ASSOC GOVT,SAN DIEGO,CA.
RP SWANSON, DA (reprint author), UNIV ARKANSAS,ARKANSAS INST ECON ADVANCEMENT,2801 S UNIV AVE,LITTLE ROCK,AR 72204, USA.
NR 49
TC 13
Z9 14
U1 0
U2 0
PU KLUWER ACADEMIC PUBL
PI DORDRECHT
PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
SN 0167-5923
J9 POPUL RES POLICY REV
JI Popul. Res. Policy Rev.
PD JUN
PY 1995
VL 14
IS 2
BP 233
EP 249
DI 10.1007/BF01074460
PG 17
WC Demography
SC Demography
GA RP550
UT WOS:A1995RP55000005
ER

PT J
AU ALDROUBI, A
AF ALDROUBI, A
TI PORTRAITS OF FRAMES
SO PROCEEDINGS OF THE AMERICAN MATHEMATICAL SOCIETY
LA English
DT Article
DE FRAMES; FRAME-PRESERVING MAPPINGS; AFFINE FRAMES; MULTIRESOLUTION;
   WAVELETS
ID WAVELET TRANSFORMS; MULTIRESOLUTION
AB We introduce two methods for generating frames of a Hilbert space H. The first method uses bounded operators on H. The other method uses bounded linear operators on it to generate frames of H. We characterize all the mappings that transform frames into other frames. We also show how to construct all frames of a given Hilbert space H, starting from any given one. We illustrate the results by giving some examples from multiresolution and wavelet theory.
C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NTTT,BETHESDA,MD 20894.
RI Aldroubi, Akram/J-7186-2012
NR 17
TC 56
Z9 59
U1 0
U2 3
PU AMER MATHEMATICAL SOC
PI PROVIDENCE
PA 201 CHARLES ST, PROVIDENCE, RI 02940-2213
SN 0002-9939
J9 P AM MATH SOC
JI Proc. Amer. Math. Soc.
PD JUN
PY 1995
VL 123
IS 6
BP 1661
EP 1668
DI 10.2307/2160974
PG 8
WC Mathematics, Applied; Mathematics
SC Mathematics
GA QZ345
UT WOS:A1995QZ34500005
ER

PT J
AU CAO, J
   FALES, HM
   SCHAFFNER, CP
AF CAO, J
   FALES, HM
   SCHAFFNER, CP
TI CELLULAR STEROL ACCUMULATION STIMULATED BY CHOLESTEROL
   5-BETA,6-BETA-EPOXIDE IN J774 MACROPHAGES
SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVELY MODIFIED LDL; SMOOTH-MUSCLE CELLS;
   ENDOTHELIAL-CELLS; ATHEROSCLEROTIC LESIONS; LIPID-PEROXIDATION;
   IDENTIFICATION; ESTERIFICATION; DEGRADATION; RECEPTOR
AB A significant accumulation of cellular free cholesterol and steryl esters is observed in 5774 macrophages when cells are exposed to low-density lipoproteins (LDL) containing cholesterol 5 beta,6 beta-epoxide. This cellular sterol accumulation is mainly due to the formation of esterified cholesterol and desmosterol. Cellular steryl esters increased to 39.4 and 22.4 mu g/mg cell protein with 0.8 mu M of cholesterol 5 beta,6 beta-epoxide and 3,5-cholestadien-7-one, respectively, whereas hardly detectable levels were observed with the absence of oxysterols. The total cellular sterols increased 45% above the value of control with cholesterol 5 beta,6 beta-epoxide. The uptake of [H-3] cholesteryl oleate-LDL was also enhanced by cholesterol 5 beta,6 beta-epoxide. The rapid displacement of desmosterol with cholesterol was observed when cells were treated with cholesterol 5 beta,6 beta-epoxide or 3,5-cholestadien-7-one in the presence of LDL. Cholesterol 5 beta,6 beta-epoxide became associated with LDL in the culture conditions, and its uptake into 5774 cells and the cytotoxicity were reduced significantly by the association with LDL. The comparison of selected oxysterols for their ability to stimulate cellular sterol accumulation indicated that cholesterol 5 beta,6 beta-epoxide is the most potent. Cholesterol esterification was enhanced significantly by cholesterol 5 beta,6 beta-epoxide whereas cholesterol 5 alpha,6 alpha-epoxide and 3,5-cholestadien-7-one produced a modest response. In contrast, although cholestantriol, the metabolic hydrolysis product of cholesterol epoxides, also associated with LDL, it showed no stimulating effect on both cellular sterol content and sterol esterification. These results indicate that some oxysterols, such as cholesterol 5 beta,6 beta-epoxide and possibly 3,5-cholestadien-7-one, stimulate cellular sterol accumulation in J774 macrophages and may play an important role in atherogenesis.
C1 RUTGERS STATE UNIV, WAKSMAN INST, PISCATAWAY, NJ 08855 USA.
   NHLBI, BETHESDA, MD 20892 USA.
FU NCI NIH HHS [CA-46785]
NR 43
TC 13
Z9 13
U1 0
U2 1
PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE
PI CAMBRIDGE
PA 238 MAIN ST, CAMBRIDGE, MA 02142
SN 0037-9727
J9 P SOC EXP BIOL MED
JI Proc. Soc. Exp. Biol. Med.
PD JUN
PY 1995
VL 209
IS 2
BP 195
EP 204
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA RA757
UT WOS:A1995RA75700015
PM 7770472
ER

PT J
AU MUSHEGIAN, AR
   KOONIN, EV
AF MUSHEGIAN, AR
   KOONIN, EV
TI A PUTATIVE FAD-BINDING DOMAIN IN A DISTINCT GROUP OF OXIDASES INCLUDING
   A PROTEIN INVOLVED IN PLANT DEVELOPMENT
SO PROTEIN SCIENCE
LA English
DT Article
DE ARABIDOPSIS GROWTH; FAD-DEPENDENT OXIDASES; SCANNING DATABASES WITH
   ALIGNMENT BLOCKS
AB Using methods for database screening with individual protein sequences and alignment blocks, a conserved domain is delineated in a group of proteins including several FAD-dependent oxidases. Two motifs within this domain resemble phosphate-binding loops and may be directly involved in FAD binding. These motifs can be readily distinguished from previously described nucleotide-binding sites using a method for database screening with position-dependent weight matrices derived from alignment blocks. Unexpectedly, this group of known and predicted FAD-dependent oxidases includes the product of the DIMINUTO gene, which is involved in Arabidopsis development, and its homologues from man and Mycobacterium leprae.
C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894.
RP MUSHEGIAN, AR (reprint author), UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195, USA.
OI Mushegian, Arcady/0000-0002-6809-9225
NR 14
TC 41
Z9 44
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD JUN
PY 1995
VL 4
IS 6
BP 1243
EP 1244
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RF135
UT WOS:A1995RF13500023
PM 7549889
ER

PT J
AU KEHOE, EJ
   SCHREURS, BG
   MACRAE, M
   GORMEZANO, I
AF KEHOE, EJ
   SCHREURS, BG
   MACRAE, M
   GORMEZANO, I
TI EFFECTS OF MODULATING TONE FREQUENCY, INTENSITY, AND DURATION ON THE
   CLASSICALLY-CONDITIONED RABBIT NICTITATING-MEMBRANE RESPONSE
SO PSYCHOBIOLOGY
LA English
DT Article
ID CS-US INTERVALS; ORYCTOLAGUS-CUNICULUS; HIPPOCAMPAL-LESIONS; PONTINE
   NUCLEI; ACQUISITION; STIMULI; EYE; COMPOUND; SYSTEM; CORTEX
AB Theories of conditioning commonly assume that the conditioned stimulus (CS) activates a cascade of internal stimuli that govern the conditioned response (CR) on a moment-by-moment basis. As a means of manipulating the internal stimuli, in the present experiments we conducted delay conditioning using a tone CS of constant intensity and frequency. However, the subjects were tested with tones during which the frequency (Experiment 1) or intensity (Experiment 2) either increased or decreased in a continuous fashion over an 800-msec period. The experiments revealed that the test stimuli dramatically accelerated the recruitment of the CR. That is, both the initiation and peak of the CR occurred several hundred milliseconds earlier than that seen with the constant tone. CR likelihood and CR amplitude showed modest reductions. A third experiment entailed test manipulations of tone duration, which yielded only small changes in the CR's time course. The results are discussed with respect to real-time mechanisms of classical conditioning and their neural substrates in the encoding of pure tones.
C1 NIH,BETHESDA,MD 20892.
   UNIV IOWA,IOWA CITY,IA.
RP KEHOE, EJ (reprint author), UNIV NEW S WALES,SCH PSYCHOL,SYDNEY,NSW 2052,AUSTRALIA.
OI Schreurs, Bernard/0000-0002-5776-0807
NR 61
TC 5
Z9 5
U1 0
U2 1
PU PSYCHONOMIC SOC INC
PI AUSTIN
PA 1710 FORTVIEW RD, AUSTIN, TX 78704
SN 0889-6313
J9 PSYCHOBIOLOGY
JI Psychobiology
PD JUN
PY 1995
VL 23
IS 2
BP 103
EP 115
PG 13
WC Psychology; Psychology, Multidisciplinary
SC Psychology
GA RF138
UT WOS:A1995RF13800002
ER

PT J
AU LAMB, ME
   STERNBERG, KJ
   ESPLIN, PW
AF LAMB, ME
   STERNBERG, KJ
   ESPLIN, PW
TI MAKING CHILDREN INTO COMPETENT WITNESSES - REACTIONS TO THE AMICUS BRIEF
   IN-RE MICHAELS
SO PSYCHOLOGY PUBLIC POLICY AND LAW
LA English
DT Article
ID MEMORY; SUGGESTIBILITY
AB In their amicus brief, M. Bruck and S. J. Ceci (1993/1995) highlight the many ways in which children's competence and informativeness can be undercut by incompetent investigative procedures and interview techniques. In this article, the authors discuss ways in which skilled interviewers, with realistic goals regarding the amount and quality of information that can be obtained from young informants, can instead enhance the quality of children's accounts. The discussion of these issues is informed by a review of the scholarly literatures on children's memory, communicative styles and skills, and suggestibility, as well as by field research on the usefulness of different interview strategies.
RP LAMB, ME (reprint author), NICHHD, SOCIAL & EMOT DEV SECT, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA.
NR 57
TC 34
Z9 34
U1 0
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1076-8971
J9 PSYCHOL PUBLIC POL L
JI Psychol. Public Policy Law
PD JUN
PY 1995
VL 1
IS 2
BP 438
EP 449
DI 10.1037/1076-8971.1.2.438
PG 12
WC Health Policy & Services; Law; Psychology, Multidisciplinary
SC Health Care Sciences & Services; Government & Law; Psychology
GA RZ610
UT WOS:A1995RZ61000011
ER

PT J
AU STATHIS, M
   SCHEFFEL, U
   LEVER, SZ
   BOJA, JW
   CARROLL, FI
   KUHAR, MJ
AF STATHIS, M
   SCHEFFEL, U
   LEVER, SZ
   BOJA, JW
   CARROLL, FI
   KUHAR, MJ
TI RATE OF BINDING OF VARIOUS INHIBITORS AT THE DOPAMINE TRANSPORTER
   IN-VIVO
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE DOPAMINE TRANSPORTER; COCAINE ANALOGS; MOUSE STRIATUM
ID AGONIST-INDUCED DESENSITIZATION; RELATIVE ABUSE LIABILITY; I-123
   BETA-CIT; COCAINE RECEPTORS; SQUIRREL-MONKEYS; SEROTONIN TRANSPORTERS;
   LIQUID-CHROMATOGRAPHY; REUPTAKE INHIBITORS; NONHUMAN-PRIMATES; H-3
   WIN-35,428
AB The rate of entry of drugs into brain is thought to be a factor in their abuse liability In this investigation, we have examined the rate of entry and binding at dopamine transporters in mouse striatum for a variety of dopamine transporter inhibitors. The method utilized was based on measuring the displacement of H-3-WIN 35,428 from striatal dopamine transporter sites in vivo at different times. Eleven cocaine analogs (RTI-31, RTI-32, RTI-51, RTI-55, RTI-113, RTI-114, RTI-117, RTI-120, RTI-121, WIN 35,065-2, and WIN 35,428) as well as other dopamine uptake site blockers (bupropion, nomifensine, and methylphenidate) were compared with (-)cocaine for their rates of displacement of H-3-WIN 35,428 binding in vivo. The drugs that displayed the fastest occupancy rates were bupropion, (-) cocaine, nomifensine, and methylphenidate. RTI-51, RTI-121, RTI-114, RTI-117, RTI-120, RTI-32, RTI-55, and RTI-113, showed intermediate rates, whereas RTI-31, WIN 35,065-2, and WIN 35,428 exhibited the slowest rates of displacement. While many of the cocaine analogs have proven to be behaviorally and pharmacologically more potent than (-) cocaine, their rates of entry and binding site occupancy were slower than that for (-) cocaine. Earliest times of transporter occupancy by the different drugs were correlated (although weakly) with their degree of lipophilicity (r = 0.59; P < 0.02). Kinetic effects and metabolism of the compounds could complicate the interpretations of these data. There was no obvious correlation between rate of occupancy in this animal model and abuse liability in humans, which is consistent with the notion that other factors are critical as well.
C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224.
   JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,DIV RADIAT HLTH,BALTIMORE,MD 21205.
   RES TRIANGLE INST,RES TRIANGLE PK,NC 27709.
NR 64
TC 64
Z9 64
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 JUN
PY 1995
VL 119
IS 4
BP 376
EP 384
DI 10.1007/BF02245852
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA RG451
UT WOS:A1995RG45100004
PM 7480516
ER

PT J
AU GESELOWITZ, DA
   MCMANAWAY, ME
   HOFER, KG
   NEUMANN, RD
AF GESELOWITZ, DA
   MCMANAWAY, ME
   HOFER, KG
   NEUMANN, RD
TI THE CYTOTOXICITY OF DECAYS OF TRITIUM AND I-125 INCORPORATED IN DNA OF
   MAMMALIAN-CELLS - IMPLICATIONS FOR THE LOW-LET DOSIMETRY OF INCORPORATED
   NUCLIDES
SO RADIATION RESEARCH
LA English
DT Article
ID INDUCED DIVISION DELAY; I-125; RADIOTOXICITY; INACTIVATION
AB To quantify the toxicity of low-LET radiation from incorporated radionuclides, we have determined the toxicity of decays of [H-3]dThd pulse-incorporated into CHO cells in early S phase, with the cells frozen for decay accumulation at 30, 120 or 360 min after the pulse. D-37 values of 1500, 2000 and 2100 decays were found by colony formation assay, corresponding to average nuclear doses of 4.6 and 2.7 Gy at the 30- and 360-min times. As D-37 for external irradiation (Co-60, 2.2 Gy/min) under these conditions is approximately 18 Gy, these results confirm the inadequacy of the dosimetry used for external irradiation to predict the biological effects of the low-LET radiation from incorporated radionuclides. We also determined the toxicity of (125)IdU administered as above, and have confirmed the previously reported finding that D-37 falls dramatically from 165 decays at 30 min to 40 decays at 360 min. Using the data for tritium to estimate the effect of the dose of I-125 low-LET radiation, we conclude that even at 30 min, most of the toxicity of the I-125 decays is due to the high-LET portion of the I-125 electron spectrum, not the low-LET portion as reported previously. (C) 1995 by Radiation Research Society
C1 FLORIDA STATE UNIV,INST MOLEC BIOPHYS,TALLAHASSEE,FL 32306.
RP GESELOWITZ, DA (reprint author), NIH,CTR CLIN,DEPT NUCL MED,BLDG 10,ROOM 1C401,10 CTR DR MSC 1180,BETHESDA,MD 20892, USA.
NR 15
TC 10
Z9 10
U1 0
U2 1
PU RADIATION RESEARCH SOC
PI OAK BROOK
PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD JUN
PY 1995
VL 142
IS 3
BP 321
EP 326
DI 10.2307/3579141
PG 6
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
   Nuclear Medicine & Medical Imaging
GA RB500
UT WOS:A1995RB50000010
PM 7761582
ER

PT J
AU DEMERS, PA
   BOFFETTA, P
   KOGEVINAS, M
   BLAIR, A
   MILLER, BA
   ROBINSON, CF
   ROSCOE, RJ
   WINTER, PD
   COLIN, D
   MATOS, E
   VAINIO, H
AF DEMERS, PA
   BOFFETTA, P
   KOGEVINAS, M
   BLAIR, A
   MILLER, BA
   ROBINSON, CF
   ROSCOE, RJ
   WINTER, PD
   COLIN, D
   MATOS, E
   VAINIO, H
TI POOLED REANALYSIS OF CANCER MORTALITY AMONG 5 COHORTS OF WORKERS IN
   WOOD-RELATED INDUSTRIES
SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH
LA English
DT Article
DE WOOD DUST; MULTIPLE MYELOMA; NASAL CANCER; NASOPHARYNGEAL CANCER;
   OCCUPATIONAL DISEASES
ID HIGH-WYCOMBE AREA; MULTIPLE-MYELOMA; DUST EXPOSURE; FURNITURE;
   MISCLASSIFICATION; EPIDEMIOLOGY; FORMALDEHYDE; MAKERS; RISK
AB Objectives To provide more information regarding the risk of cancer associated with wood dust, a pooled reanalysis of data from five cohort studies was performed.
   Methods The combined cohort consisted of 28 704 persons from five studies: British furniture workers, members of the union representing furniture workers in the United States, two cohorts of plywood workers, and one of wood model makers, among whom 7665 deaths occurred. Pooled analyses were carried out for all of the cohorts combined, the two furniture worker cohorts combined, and the two plywood workers cohorts combined.
   Results Significant excesses of nasal [observed 11, standardized mortality ratio (SMR) 3.1, 95% confidence interval (95% CI) 1.6-5.6] and nasopharyngeal (observed 9, SMR 2.4, 95% CI 1.1-4.5) cancer were observed. That for nasal cancer appeared to be associated with exposure to wood dust but was based solely on cases from the British furniture worker cohort, while that of nasopharyngeal cancer was observed for furniture and plywood workers and was associated with both high and low probability of wood dust exposure. Some support for an excess risk of multiple myeloma was also observed but was less clearly associated with wood dust exposure. No excesses of lung, larynx, stomach, or colon cancer were found to be associated with any surrogate indicators of wood dust exposure.
   Conclusions Workers exposed to wood dust may have an excess risk of nasopharyngeal cancer and multiple myeloma in addition to sinonasal cancer. The limitations of this study would tend to obscure relationships, rather than create false positive findings.
C1 INT AGCY RES CANC,F-69372 LYON,FRANCE.
   INST MUNICIPAL INVEST MED,BARCELONA,SPAIN.
   NCI,BETHESDA,MD 20892.
   NIOSH,CINCINNATI,OH 45226.
   MRC,LONDON,ENGLAND.
   INST ONCOL ANGEL H ROFFO,BUENOS AIRES,DF,ARGENTINA.
   INST OCCUPAT HLTH,HELSINKI,FINLAND.
RP DEMERS, PA (reprint author), UNIV BRITISH COLUMBIA,OCCUPAT HYG PROGRAMME,2206 EAST MALL,3RD FLOOR,VANCOUVER,BC V6T 1Z3,CANADA.
RI Kogevinas, Manolis/C-3918-2017
NR 40
TC 70
Z9 70
U1 1
U2 5
PU SCAND J WORK ENV HEALTH
PI HELSINKI
PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND
SN 0355-3140
J9 SCAND J WORK ENV HEA
JI Scand. J. Work Environ. Health
PD JUN
PY 1995
VL 21
IS 3
BP 179
EP 190
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA RJ198
UT WOS:A1995RJ19800003
PM 7481605
ER

PT J
AU REED, E
   KOHN, EC
   SAROSY, G
   DABHOLKAR, M
   DAVIS, P
   JACOB, J
   MAHER, M
AF REED, E
   KOHN, EC
   SAROSY, G
   DABHOLKAR, M
   DAVIS, P
   JACOB, J
   MAHER, M
TI PACLITAXEL, CISPLATIN, AND CYCLOPHOSPHAMIDE IN HUMAN OVARIAN-CANCER -
   MOLECULAR RATIONALE AND EARLY CLINICAL-RESULTS
SO SEMINARS IN ONCOLOGY
LA English
DT Article; Proceedings Paper
CT Fox-Chase-Cancer-Center Paclitaxel Investigators Workshop on the
   Emerging Role of Paclitaxel in Cancer Chemotherapy
CY FEB 23-27, 1994
CL BOCA RATON, FL
SP Fox Chase Canc Ctr, Bristol Myers Squibb Co
ID DOSE INTENSITY ANALYSIS; CHEMOTHERAPY REGIMENS; TAXOL; CELLS; RADIATION;
   CARCINOMA; ABSENCE
RP REED, E (reprint author), NCI,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,BLDG 10, ROOM 12N226,BETHESDA,MD 20892, USA.
NR 26
TC 44
Z9 44
U1 1
U2 2
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 1995
VL 22
IS 3
SU 6
BP 90
EP 96
PG 7
WC Oncology
SC Oncology
GA RG875
UT WOS:A1995RG87500018
PM 7541159
ER

PT J
AU YOUNG, HA
AF YOUNG, HA
TI REGULATION OF INTERFERON-GAMMA GENE-TRANSCRIPTION
SO SEMINARS IN VIROLOGY
LA English
DT Article
DE INTERFERON-GAMMA; TRANSCRIPTION; METHYLATION DNA
ID LARGE GRANULAR LYMPHOCYTES; HUMAN T-CELLS; IFN-GAMMA; INTERLEUKIN-2;
   INDUCTION; EXPRESSION; ACTIVATION; PROMOTER; LINE; LIPOPOLYSACCHARIDE
AB Interferon-gamma, a type II interferon, is an important immunoregulatory molecule whose initial biological properties were first reported in 1965. Although the effects of IFN gamma in vitro and in vive and at the molecular level have been widely investigated, the transcriptional control of this single copy gene has not been as extensively studied. In this review I will attempt to summarize what is known about the role of DNA binding proteins and genomic DNA regulatory regions in the regulation of transcription of the IFN gamma gene. Current data suggests that transcriptional regulation involves DNA methylation and the interaction of multiple different DNA binding proteins with both promoter and intronic enhancer and suppressor elements.
RP YOUNG, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA.
NR 46
TC 7
Z9 7
U1 0
U2 0
PU ACADEMIC PRESS (LONDON) LTD
PI LONDON
PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX
SN 1044-5773
J9 SEMIN VIROL
JI Semin. Virol.
PD JUN
PY 1995
VL 6
IS 3
BP 175
EP 179
DI 10.1006/smvy.1995.0022
PG 5
WC Virology
SC Virology
GA RN111
UT WOS:A1995RN11100005
ER

PT J
AU CLORE, GM
   GRONENBORN, AM
AF CLORE, GM
   GRONENBORN, AM
TI 3-DIMENSIONAL AND 4-DIMENSIONAL HETERONUCLEAR NMR
SO SPECTROSCOPY
LA English
DT Article
ID MAGNETIC-RESONANCE SPECTROSCOPY; 3-DIMENSIONAL SOLUTION STRUCTURE;
   PROTEIN-STRUCTURE DETERMINATION; PULSED-FIELD GRADIENTS; SIDE-CHAIN
   RESONANCES; LARGER PROTEINS; C-13/N-15-ENRICHED PROTEINS; HUMAN
   INTERLEUKIN-4; HIGH-RESOLUTION; C-13-LABELED PROTEINS
C1 NIH,CHEM PHYS LAB,BETHESDA,MD 20892.
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
NR 53
TC 0
Z9 0
U1 0
U2 0
PU ADVANSTAR COMMUNICATIONS
PI DULUTH
PA 131 W FIRST ST, DULUTH, MN 55802
SN 0887-6703
J9 SPECTROSCOPY
JI Spectroscopy
PD JUN
PY 1995
VL 10
IS 5
BP 32
EP 38
PG 7
WC Spectroscopy
SC Spectroscopy
GA RF257
UT WOS:A1995RF25700006
ER

PT J
AU FRAKER, DL
AF FRAKER, DL
TI RADIATION EXPOSURE AND OTHER FACTORS THAT PREDISPOSE TO HUMAN THYROID
   NEOPLASIA
SO SURGICAL CLINICS OF NORTH AMERICA
LA English
DT Article
ID RETROSPECTIVE COHORT; CANCER; DISEASE; CARCINOMA; FALLOUT; THERAPY;
   TUMORS; WOMEN; I-131
AB Radiation exposure is the only known etiologic factor clearly associated with an increased risk of thyroid cancer. External beam radiation treatment for medical therapy, acute gamma ray exposure from environmental sources (nuclear weapons, nuclear power plant accidents), and ingestion of short-lived radioactive iodine isotopes are the primary sources of radiation exposure, which increases the risk of benign and malignant thyroid neoplasia. Relative risk is directly proportional to the exposure dose and is inversely proportional to the age at exposure.
RP FRAKER, DL (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA.
NR 20
TC 16
Z9 17
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0039-6109
J9 SURG CLIN N AM
JI Surg. Clin.-North Am.
PD JUN
PY 1995
VL 75
IS 3
BP 365
EP 375
PG 11
WC Surgery
SC Surgery
GA QY635
UT WOS:A1995QY63500003
PM 7747246
ER

PT J
AU LIPSKA, BK
   CHRAPUSTA, SJ
   EGAN, MF
   WEINBERGER, DR
AF LIPSKA, BK
   CHRAPUSTA, SJ
   EGAN, MF
   WEINBERGER, DR
TI NEONATAL EXCITOTOXIC VENTRAL HIPPOCAMPAL DAMAGE ALTERS DOPAMINE RESPONSE
   TO MILD REPEATED STRESS AND TO CHRONIC HALOPERIDOL
SO SYNAPSE
LA English
DT Article
DE HIPPOCAMPUS; NEONATAL LESION; IBOTENIC ACID; STRESS; HALOPERIDOL;
   3-METHOXYTYRAMINE; DOPAMINE RELEASE
ID NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; ANTEROGRADE TRANSPORT; MESOLIMBIC
   SYSTEM; FRONTAL-CORTEX; RAT; RELEASE; STRIATUM; NEURONS; INVIVO
AB The effects of neonatal excitotoxic ventral hippocampus (VH) lesions on dopamine release in response to repeated stress (saline injections) and to chronic haloperidol treatment were investigated in Sprague-Dawley rats infused with ibotenic acid or vehicle into the VH on day 7 of postnatal life (PD7). Beginning on PD35, lesioned and sham-operated rats were injected i.p. with saline (INJ) once daily for 3 weeks or were not treated (NO INJ). Another cohort of rats was given haloperidol (HAL, 0.4 mg/kg, i.p.) or vehicle beginning on PD35 and thereafter once daily for 3 weeks. 3-Methoxytyramine (3-MT) was measured by combined gas chromatography/mass spectrometry in the frontal cortex (FC), nucleus accumbens (NAcc), and striatum (STR) at PD56 following MAO inhibition with pargyline. At baseline (NO INJ), 3-MT was reduced in STR of lesioned rats. Repeated saline injections resulted in a further 3-MT reduction in STR, FC, and NAcc of lesioned animals, but had no effect in sham rats. Chronic HAL, compared with vehicle, suppressed locomotor activity, and increased 3-MT accumulation in the FC, NAcc, and STR in sham and lesioned rats. This increase was enhanced in the FC of lesioned rats. These data show that mild repeated stress attenuates dopamine release in FC, NAcc, and STR of lesioned rats, while chronic HAL augments it in FC of lesioned animals versus controls. We conclude that the neonatal excitotoxic lesion of VH alters the functioning of midbrain dopamine systems during environmental and pharmacological challenge. (C) 1995 Wiley-Liss, Inc.*
RP LIPSKA, BK (reprint author), NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA.
RI Lipska, Barbara/E-4569-2017
NR 35
TC 69
Z9 70
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD JUN
PY 1995
VL 20
IS 2
BP 125
EP 130
DI 10.1002/syn.890200205
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA RA485
UT WOS:A1995RA48500004
PM 7570341
ER

PT J
AU RAIFE, TJ
   DEMETROULIS, EM
   RHIM, JS
   LENTZ, SR
AF RAIFE, TJ
   DEMETROULIS, EM
   RHIM, JS
   LENTZ, SR
TI REGULATION OF KERATINOCYTE THROMBOMODULIN BY RETINOIC ACID
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242.
   UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242.
   NCI,MOLEC ONCOL LAB,BETHESDA,MD 20892.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU F K SCHATTAUER VERLAG GMBH
PI STUTTGART
PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUN
PY 1995
VL 73
IS 6
BP 947
EP 947
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA RP385
UT WOS:A1995RP38500188
ER

PT J
AU VERKLEII, M
   SAELMAN, E
   GRALNICK, HR
   VONZANTEN, H
   IJSSELDIJK, M
   NIEUWENHUIS, HK
   SIXMA, JJ
AF VERKLEII, M
   SAELMAN, E
   GRALNICK, HR
   VONZANTEN, H
   IJSSELDIJK, M
   NIEUWENHUIS, HK
   SIXMA, JJ
TI GLYCOPROTEIN-IA/IIA HAS A ROLE IN PLATELET-ADHESION TO SURFACES FOR
   WHICH IT IS NOT THE RECEPTOR
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 UNIV UTRECHT HOSP,DEPT HEMATOL,3511 GV UTRECHT,NETHERLANDS.
   NIH,CTR CLIN,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU F K SCHATTAUER VERLAG GMBH
PI STUTTGART
PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUN
PY 1995
VL 73
IS 6
BP 1202
EP 1202
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA RP385
UT WOS:A1995RP38501155
ER

PT J
AU FANELLI, A
   BERLIN, WK
   GROLLMAN, EF
AF FANELLI, A
   BERLIN, WK
   GROLLMAN, EF
TI INHIBITION OF IODIDE TRANSPORT IN RAT-THYROID CELLS USING N-SUBSTITUTED
   ANTHRANILIC ACID-DERIVATIVES
SO THYROID
LA English
DT Article
ID CHLORIDE CHANNELS; MEMBRANE-VESICLES; THYROTROPIN; PH
AB The purpose of this study was to test the effects of chloride channel blockers on iodide uptake in thyroid cells, in the hope of eventually using these blockers to identify and isolate a putative iodide transporter, The chloride channel blockers used in this report are derivatives of N-substituted anthranilic acid and were synthesized using published procedures, For these studies FRTL-5 cells, a line of continuous-growing rat thyroid cells, were used as a model system to study effects on iodide transport. In these cells, there are at least two ways for transmembrane iodide movements, a sodium-dependent influx step and a proposed channel that normally mediates iodide efflux, Two derivatives studied decreased iodide accumulation in FRTL-5 cells, but were found also to lower intracellular pH and ATP levels, To simplify interpretation of the effect of the drugs on iodide transport, we extended the studies using plasma membrane vesicles made from pig thyroid, Iodide entry in these vesicles depended on a sodium gradient and was independent of ATP levels, Iodide transport in plasma membrane vesicles and FRTL-5 cells was measured at 30 sec when the uptake was nearly linear and therefore likely to reflect iodide entry, The uptake was measured using three concentrations of iodide and three of drug. Kinetic analysis of the data described a competitive inhibition by the drugs with a K-i of approximately 250 mu M. In summary, N-substituted anthranilic acid derivatives reversibly inhibit iodide entry in FRTL-5 cells and pig plasma membrane vesicles, Because of their ease of synthesis and modification, these derivatives are potentially useful probes for isolation of the NaI symporter in thyroid.
C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892.
NR 23
TC 4
Z9 4
U1 0
U2 0
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUN
PY 1995
VL 5
IS 3
BP 223
EP 230
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA RL220
UT WOS:A1995RL22000012
PM 7580272
ER

PT J
AU SEWALL, CH
   FLAGLER, N
   VANDENHEUVEL, JP
   CLARK, GC
   TRITSCHER, AM
   MARONPOT, RM
   LUCIER, GW
AF SEWALL, CH
   FLAGLER, N
   VANDENHEUVEL, JP
   CLARK, GC
   TRITSCHER, AM
   MARONPOT, RM
   LUCIER, GW
TI ALTERATIONS IN THYROID-FUNCTION IN FEMALE SPRAGUE-DAWLEY RATS FOLLOWING
   CHRONIC TREATMENT WITH 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
ID MICROSOMAL-ENZYME-INDUCTION; DOSE-RESPONSE RELATIONSHIPS; HORMONE
   LEVELS; CANCER MORTALITY; THYROXINE; DIOXINS; TCDD; CARCINOGENESIS;
   METABOLISM; RECEPTOR
AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multisite carcinogen. Although the hepatocarcinogenic actions of TCDD have received the most attention, it has been demonstrated in several rodent carcinogenicity bioassays that TCDD causes a dose-related increase in thyroid follicular cell adenomas and carcinomas. The purpose of the present experiment was to investigate the dose-response relationship for thyroid function alterations in female Sprague-Dawley rats following chronic treatment with TCDD. TCDD was administered via oral gavage biweekly for 30 weeks at average daily equivalent doses of 0.1-125 ng/kg/day, thereby more than encompassing the dose range historically used in previous TCDD rodent bioassays. The endpoints examined include serum levels of thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH). In addition, the induction of the dioxin-responsive genes UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P450 1A1 (CYP1A1) in liver were measured using reverse-transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous hypotheses, TCDD appears to alter thyroid function via a secondary mechanism, namely increased excretion of T4-glucuronide resulting from TCDD induction of UGT1. The observed follicular cell hyperplasia and hypertrophy are consistent with the observed elevated TSH levels and may represent the early stages in the progression of thyroid carcinogenesis. Therefore, TCDD induces alterations in thyroid hormone function, probably as a result of chronic perturbations of liver-pituitary-thyroid axis. (C) 1995 Academic Press, Inc.
C1 UNIV N CAROLINA, CURRICULUM TOXICOL, CHAPEL HILL, NC 27514 USA.
   PURDUE UNIV, DEPT PHARMACOL, LAFAYETTE, IN 47907 USA.
RP NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA.
NR 48
TC 59
Z9 60
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUN
PY 1995
VL 132
IS 2
BP 237
EP 244
DI 10.1006/taap.1995.1104
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA RC275
UT WOS:A1995RC27500007
PM 7540335
ER

PT J
AU SEWALL, CH
   CLARK, GC
   LUCIER, GW
AF SEWALL, CH
   CLARK, GC
   LUCIER, GW
TI TCDD REDUCES RAT HEPATIC EPIDERMAL GROWTH-FACTOR RECEPTOR - COMPARISON
   OF BINDING, IMMUNODETECTION, AND AUTOPHOSPHORYLATION
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
ID EPITHELIAL-CELL DIFFERENTIATION; RETROVIRUS-LIKE SEQUENCES;
   2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; GLUCOCORTICOID RECEPTOR;
   CANCER MORTALITY; DIOXIN RECEPTOR; PLASMA-MEMBRANE; C57BL/6J MICE; EGF
   RECEPTOR; AH LOCUS
AB Administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent tumor promoter, to rats resulted in a dose-dependent decrease in hepatic plasma membrane epidermal growth factor receptor (EGFR). The present study is the first to quantify and compare alterations in hepatic EGFR levels in female Sprague-Dawley rats 7 days after a single oral gavage dose of TCDD (0, 1, 5, 25, and 50 mu g/kg) using three different techniques: (I)equilibrium receptor binding, (2) EGF induced receptor autophosphorylation, and (3) Western blot detection with a rabbit anti-rat EGFR polyclonal antibody. All three methods similarly demonstrated that the level of hepatic EGFR is significantly decreased at a dose of TCDD as low as 1 mu g/kg. We shelved that the immunoblot technique is a sensitive and quantitative alternative to radioligand binding assays. It is concluded that TCDD decreased total EGFR protein and maximum binding capacity without altering ligand binding affinity (K-d). The results demonstrated that ligand-induced autophosphorylation capacity and basal phosphotyrosine residues of plasma membrane EGFR were both decreased parallel with the decrease in EGFR protein, suggesting no TCDD-related alteration in the inherent functional ability of the receptor to undergo activation. Furthermore, it was found that the dose-response curve for EGFR protein level determined by Western blot analysis was similar for both male and female Sprague-Dawley rats. (C) 1995 Academic Press, Inc.
C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC.
RP SEWALL, CH (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA.
NR 73
TC 35
Z9 35
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 JUN
PY 1995
VL 132
IS 2
BP 263
EP 272
DI 10.1006/taap.1995.1107
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA RC275
UT WOS:A1995RC27500010
PM 7785053
ER

PT J
AU DRAGNEV, KH
   NIMS, RW
   FOX, SD
   LINDAHL, R
   LUBET, RA
AF DRAGNEV, KH
   NIMS, RW
   FOX, SD
   LINDAHL, R
   LUBET, RA
TI RELATIVE POTENCIES OF INDUCTION OF HEPATIC DRUG-METABOLIZING ENZYME
   GENES BY INDIVIDUAL PCB CONGENERS
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS PCBS; XENOBIOTIC RESPONSE ELEMENT; ALDEHYDE
   DEHYDROGENASE; MESSENGER-RNA; AH RECEPTOR; INDUCIBLE EXPRESSION;
   NUCLEOTIDE-SEQUENCE; DIETARY EXPOSURE; RISK ASSESSMENT; MOUSE-LIVER
AB The induction of a variety of drug-metabolizing enzymes by polychlorinated biphenyl (PCB) congeners that elicit a 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD)-type hepatic pleiotropic response, including 2,3,3',4,4'-pentachlorobiphenyl (BZ 105), 2,3',4,4',5-pentachlorobiphenyl (BZ 118), 2,3,3',4,4',5-hexachlorobiphenyl (BZ 156), and 3,3',4,4',5,5'-hexachlorobiphenyl (BZ 169) was examined. Following dietary exposure to the individual congeners for 5 days, livers were removed and catalytic assays for cytochrome P450 (CYP) isozymes 1A1 and 1A2 were performed. Additionally, total cellular RNA coding for hepatic drug-metabolizing genes (CYP 1A1, CYP 1A2, microsomal epoxide hydrolase, glutathione S-transferase [GST] Ya/Yc, and the TCDD-inducible isozyme of aldehyde dehydrogenase [ALDH] was quantified. 3-Methylcholanthrene (MC), TCDD, or BZ 156 (32 ppm) caused nearly maximal induction of the CYP 1A proteins but lower induction of the other genes. When the dose-response curves for induction of various drug-metabolizing genes (CYP1A1 and 1A2, microsomal epoxide hydrolase, the GST Ya/Yc subfamily and ALDH) were examined, a spectrum of ED50s (half-maximal inductions) was observed. While CYP 1A2 exhibited an ED50 of 1.7 ppm, the induction of ALDH was shifted far to the right (ED50 > 11 ppm). Thus, different genes in a single tissue may display different dose-response characteristics. The potency (extent of induction of CYP 1A1 activity resulting from a given dietary dose) was BZ 169 much greater than BZ 156 > BZ 118 > BZ 105. In contrast, the potencies of the four congeners for CYP 1A1 induction were nearly equivalent when related to hepatic PCB burden, apparently due to the preferential accumulation in the liver of BZs 169 and 156 following low-level administration in the diet. (C) 1995 Academic Press, Inc.
C1 NCI,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTHESIS & ANAL LAB,FREDERICK,MD 21702.
   UNIV S DAKOTA,SCH MED,DEPT BIOCHEM & MOLEC BIOL,VERMILLION,SD 57069.
NR 51
TC 18
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 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUN
PY 1995
VL 132
IS 2
BP 334
EP 342
DI 10.1006/taap.1995.1115
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA RC275
UT WOS:A1995RC27500018
PM 7785061
ER

PT J
AU CABLE, RG
   THAL, SE
   FINK, A
   CALHOUN, L
   PETZ, LD
   CROWLEY, JP
   MOR, V
   GOODNOUGH, LT
   HULL, A
   WHITSETT, CF
   SULLIVAN, C
   SIMPSON, MB
   SILVER, S
   KRUSKALL, MS
   BRENNAN, R
   SMITH, JE
   BAILEY, GD
   GOTTSCHALL, JL
   SIMPSON, DE
   JETER, EK
   FLEMING, GA
   SCHWARTZ, KA
   BRIDGHAM, R
   BULL, RW
   BRIDGHAM, RG
   ROSSI, EC
   KENNEDY, MS
   PEARSOL, JA
   SPENCE, RK
   DAVIDSON, R
   JOHNSTON, MFM
   STEHLING, L
   DRACKER, RA
   EISENSTAEDT, RS
   GLANZ, K
   COTTER, SM
   FELDMAN, R
   TOY, PTCY
   ROSINSKI, E
   GREENWALT, TJ
   AMBRUSO, DR
   HOUSE, E
   HOWE, K
   THAL, S
   STRAUSS, RG
   MITCHELL, S
   SZYMANSKI, IO
   ANDERSON, SM
   LENES, BA
   JASON, H
   MAHAN, JM
   WARKENTIN, PI
   MANNING, BA
   LEACH, M
   SIMON, TL
   SMITH, K
   ODONNELL, MJ
   COLLINS, ML
   STRITTER, FT
   JEFFRIES, LC
   DISERENS, D
   GIGER, U
   VELEZ, R
   PATTEN, ED
   PETRUSA, ER
   WESTPHAL, RG
   MCPHERSON, B
   MINTZ, PD
   SHORT, JG
   FANG, WL
   PRICE, TH
   WOODSON, RD
   STONE, HL
   MEYERS, KM
   MINER, D
   LUSHER, JM
   GALLAGHER, R
   SNYDER, EL
   FARACLAS, W
   HARDING, F
   ROTH, C
AF CABLE, RG
   THAL, SE
   FINK, A
   CALHOUN, L
   PETZ, LD
   CROWLEY, JP
   MOR, V
   GOODNOUGH, LT
   HULL, A
   WHITSETT, CF
   SULLIVAN, C
   SIMPSON, MB
   SILVER, S
   KRUSKALL, MS
   BRENNAN, R
   SMITH, JE
   BAILEY, GD
   GOTTSCHALL, JL
   SIMPSON, DE
   JETER, EK
   FLEMING, GA
   SCHWARTZ, KA
   BRIDGHAM, R
   BULL, RW
   BRIDGHAM, RG
   ROSSI, EC
   KENNEDY, MS
   PEARSOL, JA
   SPENCE, RK
   DAVIDSON, R
   JOHNSTON, MFM
   STEHLING, L
   DRACKER, RA
   EISENSTAEDT, RS
   GLANZ, K
   COTTER, SM
   FELDMAN, R
   TOY, PTCY
   ROSINSKI, E
   GREENWALT, TJ
   AMBRUSO, DR
   HOUSE, E
   HOWE, K
   THAL, S
   STRAUSS, RG
   MITCHELL, S
   SZYMANSKI, IO
   ANDERSON, SM
   LENES, BA
   JASON, H
   MAHAN, JM
   WARKENTIN, PI
   MANNING, BA
   LEACH, M
   SIMON, TL
   SMITH, K
   ODONNELL, MJ
   COLLINS, ML
   STRITTER, FT
   JEFFRIES, LC
   DISERENS, D
   GIGER, U
   VELEZ, R
   PATTEN, ED
   PETRUSA, ER
   WESTPHAL, RG
   MCPHERSON, B
   MINTZ, PD
   SHORT, JG
   FANG, WL
   PRICE, TH
   WOODSON, RD
   STONE, HL
   MEYERS, KM
   MINER, D
   LUSHER, JM
   GALLAGHER, R
   SNYDER, EL
   FARACLAS, W
   HARDING, F
   ROTH, C
TI A COMPREHENSIVE TRANSFUSION MEDICINE CURRICULUM FOR MEDICAL-STUDENTS
SO TRANSFUSION
LA English
DT Article
AB Background: The Transfusion Medicine Academic Awards (TMAA) program, sponsored by the National Heart, Lung, and Blood Institute,has provided grants to medical schools to help them develop comprehensive curricula in transfusion medicine. In 1989, the TMAA Group published a set of comprehensive curricular goals for teaching transfusion medicine. The medical student portion of this curriculum has now been revised to reflect new developments in transfusion medicine and recent trends in medical school education.
   Study Design and Methods: Two medical schools independently revised the 1989 curriculum for their students. Because significant similarities were noted between curricula of the two:institutions, the two revisions were combined and submitted to all TMAA institutions for comment. As a result, a revised medical school curriculum was developed and approved by the TMAA Group.
   Results: The revised curriculum consists of 28 objectives in six major areas of transfusion medicine. It is presented in its entirety in this article.
   Conclusion: The TMAA transfusion medicine curriculum should provide to medical schools a valuable resource for evaluating their teaching of transfusion medicine and should provide to medical school deans and curriculum committees an authoritative source of transfusion medicine expertise.
C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT PATHOL & LAB MED,DIV TRANSFUS MED,LOS ANGELES,CA 90024.
   BROWN UNIV,PROVIDENCE,RI.
   CASE WESTERN RESERVE UNIV,CLEVELAND,OH.
   EMORY UNIV,ATLANTA,GA.
   GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052.
   HARVARD UNIV,SCH MED,BOSTON,MA.
   MED COLL WISCONSIN,MILWAUKEE,WI.
   MED UNIV S CAROLINA,CHARLESTON,SC.
   MICHIGAN STATE UNIV,SCH MED,E LANSING,MI.
   MICHIGAN STATE UNIV,SCH VET,E LANSING,MI.
   NORTHWESTERN UNIV,EVANSTON,IL 60208.
   OHIO STATE UNIV,COLUMBUS,OH.
   ROBERT WOOD JOHNSON MED SCH,CAMDEN,NJ.
   ST LOUIS UNIV,ST LOUIS,MO 63103.
   SUNY SYRACUSE,SYRACUSE,NY.
   TEMPLE UNIV,PHILADELPHIA,PA.
   TUFTS UNIV,SCH VET MED,MEDFORD,MA.
   UNIV CALIF LOS ANGELES,LOS ANGELES,CA.
   UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143.
   UNIV CINCINNATI,CINCINNATI,OH.
   UNIV COLORADO,BOULDER,CO 80309.
   UNIV CONNECTICUT,STORRS,CT 06269.
   UNIV IOWA,IOWA CITY,IA 52242.
   UNIV MASSACHUSETTS,AMHERST,MA 01003.
   UNIV MIAMI,MIAMI,FL 33152.
   UNIV MISSISSIPPI,UNIVERSITY,MS 38677.
   UNIV NEBRASKA,LINCOLN,NE 68583.
   UNIV NEW MEXICO,ALBUQUERQUE,NM 87131.
   UNIV N CAROLINA,CHAPEL HILL,NC.
   UNIV PENN,SCH MED,PHILADELPHIA,PA 19104.
   UNIV PENN,SCH VET,PHILADELPHIA,PA 19104.
   UNIV PUERTO RICO,RIO PIEDRAS,PR.
   UNIV TEXAS,AUSTIN,TX.
   UNIV VERMONT,BURLINGTON,VT 05405.
   UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903.
   UNIV WASHINGTON,SEATTLE,WA.
   UNIV WISCONSIN,MADISON,WI 53706.
   WASHINGTON STATE UNIV,COLL VET MED,PULLMAN,WA.
   WAYNE STATE UNIV,DETROIT,MI 48202.
   YALE UNIV,NEW HAVEN,CT 06520.
   NHLBI,TMAA PROGRAM,BETHESDA,MD.
RP CABLE, RG (reprint author), UNIV CONNECTICUT,SCH MED,DEPT MED,DIV HEMATOL ONCOL,MC 1315,263 FARMINGTON AVE,FARMINGTON,CT 06030, USA.
OI Hull, Alan/0000-0001-8951-358X
NR 4
TC 24
Z9 25
U1 0
U2 1
PU AMER ASSOC BLOOD BANKS
PI BETHESDA
PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 1995
VL 35
IS 6
BP 465
EP 469
DI 10.1046/j.1537-2995.1995.35695288763.x
PG 5
WC Hematology
SC Hematology
GA RB832
UT WOS:A1995RB83200003
PM 7770895
ER

PT J
AU GOULD, SA
   KRUSKALL, MS
   STEHLING, LC
   TOY, PTCY
   MCCURDY, PR
   NEMO, GJ
   ROGUS, SD
   FINK, B
AF GOULD, SA
   KRUSKALL, MS
   STEHLING, LC
   TOY, PTCY
   MCCURDY, PR
   NEMO, GJ
   ROGUS, SD
   FINK, B
TI AUTOLOGOUS TRANSFUSION - CURRENT TRENDS AND RESEARCH ISSUES
SO TRANSFUSION
LA English
DT Editorial Material
ID ELECTIVE CARDIAC-SURGERY; PLATELET-RICH PLASMA; ORTHOTOPIC
   LIVER-TRANSPLANTATION; INTRAOPERATIVE AUTO-TRANSFUSION; SHED MEDIASTINAL
   BLOOD; MYOCARDIAL REVASCULARIZATION; PREOPERATIVE COLLECTION;
   ERYTHROPOIETIN THERAPY; KNEE REPLACEMENT; UNITED-STATES
C1 NHLBI,OFF PREVENT EDUC & CONTROL,BETHESDA,MD 20892.
NR 74
TC 16
Z9 16
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 JUN
PY 1995
VL 35
IS 6
BP 525
EP 531
PG 7
WC Hematology
SC Hematology
GA RB832
UT WOS:A1995RB83200015
ER

PT J
AU LANDSMAN, D
   WOLFFE, AP
AF LANDSMAN, D
   WOLFFE, AP
TI COMMON SEQUENCE AND STRUCTURAL FEATURES IN THE HEAT-SHOCK FACTOR AND ETS
   FAMILIES OF DNA-BINDING DOMAINS
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Note
ID TOOL
RP LANDSMAN, D (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA.
RI Landsman, David/C-5923-2009; 
OI Landsman, David/0000-0002-9819-6675
NR 13
TC 12
Z9 12
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 JUN
PY 1995
VL 20
IS 6
BP 225
EP 226
DI 10.1016/S0968-0004(00)89021-0
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RD117
UT WOS:A1995RD11700004
PM 7631419
ER

PT J
AU HENGEN, PN
AF HENGEN, PN
TI METHODS AND REAGENTS - ELECTROTRANSFORMATION OF ESCHERICHIA-COLI WITH
   PLASMID DNA
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Note
ID HIGH-EFFICIENCY TRANSFORMATION; ELECTROPORATION
AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some reasons for switching to electroporation to transform bacteria with plasmid DNA. For details on how to partake in the newsgroup, see the accompanying box.
RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701, USA.
NR 6
TC 3
Z9 4
U1 1
U2 3
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 JUN
PY 1995
VL 20
IS 6
BP 248
EP 249
DI 10.1016/S0968-0004(00)89028-3
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RD117
UT WOS:A1995RD11700010
PM 7631423
ER

PT J
AU KLAR, AJS
AF KLAR, AJS
TI OPINIONS ON LEFT-RIGHT AXIS FORMATION - REPLY
SO TRENDS IN GENETICS
LA English
DT Letter
ID EMBRYO; CELLS
RP KLAR, AJS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DEV GENET SECT,POB B,FREDERICK,MD 21702, USA.
NR 9
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD JUN
PY 1995
VL 11
IS 6
BP 214
EP 215
DI 10.1016/S0168-9525(00)89050-2
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA RB495
UT WOS:A1995RB49500007
ER

PT J
AU CROWE, JE
   BUI, PT
   SIBER, GR
   ELKINS, WR
   CHANOCK, RM
   MURPHY, BR
AF CROWE, JE
   BUI, PT
   SIBER, GR
   ELKINS, WR
   CHANOCK, RM
   MURPHY, BR
TI COLD PASSAGED, TEMPERATURE-SENSITIVE MUTANTS OF HUMAN RESPIRATORY
   SYNCYTIAL VIRUS (RSV) ARE HIGHLY ATTENUATED, IMMUNOGENIC, AND PROTECTIVE
   IN SERONEGATIVE CHIMPANZEES, EVEN WHEN RSV ANTIBODIES ARE INFUSED
   SHORTLY BEFORE IMMUNIZATION
SO VACCINE
LA English
DT Article
DE RESPIRATORY SYNCYTIAL VIRUS; PASSIVE ANTIBODY TRANSFER VACCINES;
   ATTENUATED; CHIMPANZEE
ID F-GLYCOPROTEIN; COTTON RATS; INFECTION; PURIFICATION; VACCINES; AGE
AB A cold-passaged (cp) temperature-sensitive (ts) RSV mutant, designated RSV cpts-530, which possesses host-range mutations acquired during 52 passages at low temperature in bovine tissue culture and one or more ts mutations induced by chemical mutagenesis (shut-off temperature 39 degrees C) was found previously to be tenfold restricted in its replication in mice as compared to wild-type virus and stable genetically in nude mice. In the current study, we introduced additional attenuating mutations, such as small-plaque (sp) or ts mutations, into cpts-530 by chemical mutagenesis with 5-fluorouracil, with the intent of obtaining derivatives of cpts-530 that were move attenuated in mice or chimpanzees and that were more stable genetically following replication in vivo. Fourteen mutants of RSV cpts-530 which had acquired an additional ts mutation were identified and found to be more restricted in replication in BALB/c mice than the cpts-530 parental strain. One mutant, designated cpts-530/1009 (shut-off temperature 36 degrees C), was 30 times more restricted in replication in the nasal turbinates of mice and threefold more restricted in the nasopharynx of seronegative chimpanzees than its cpts-530 parent. Like its parent, this mutant was highly restricted (30 000-fold) in replication in the lower respiratory tract of chimpanzees even following direct intratracheal inoculation. The cpts-530 and cpts-530/1009 mutants exhibited a high level of stability of the ts phenotype during replication in chimpanzees.
   The immunogenicity and protective efficacy of the cpts-530/1009 mutant and that of two other previously described candidate live attenuated RSV vaccines were compared in seronegative chimpanzees, some of whom were pretreated with RSV immune globulin by the intravenous route to simulate the condition of the very young infant who possesses passively acquired maternal antibodies. The three candidate vaccine strains were immunogenic and induced significant resistance to RSV challenge in both groups of chimpanzees. Interestingly, the chimpanzees infused with RSV antibodies prior to immunization were primed more effectively for an unusually high serum neutralizing antibody response to infection with challenge virus than chimpanzees which did Mot receive such antibodies. This high level booster response occurred despite marked restriction of replication of the challenge virus. Thus, the cpts-530/1009 virus and related mutants exhibit many desirable characteristics which make them promising vaccine candidates.
C1 MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA 02130.
RP CROWE, JE (reprint author), NIAID,RESP VIRUSES SECT,INFECT DIS LAB,BETHESDA,MD 20892, USA.
RI Crowe, James/B-5549-2009
OI Crowe, James/0000-0002-0049-1079
NR 18
TC 77
Z9 79
U1 0
U2 2
PU BUTTERWORTH-HEINEMANN LTD
PI OXFORD
PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUN
PY 1995
VL 13
IS 9
BP 847
EP 855
DI 10.1016/0264-410X(94)00074-W
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA RL566
UT WOS:A1995RL56600011
PM 7483808
ER

PT J
AU REMADI, S
   ISMAIL, A
   TAWIL, A
   MACGEE, W
AF REMADI, S
   ISMAIL, A
   TAWIL, A
   MACGEE, W
TI OVARIAN SERTOLIFORM ENDOMETRIOID CARCINOMA
SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
LA English
DT Note
DE OVARY; ENDOMETRIOID CARCINOMA; SERTOLI CELL TUMOR
ID CORD-STROMAL TUMORS
AB Sertoliform endometrioid carcinoma (SEC) is a rare ovarian neoplasm occurring almost exclusively in post-menopausal patients. We studied a 71-year-old patient who underwent a total hysterectomy with bilateral salpingo-oophorectomy for a right ovarian mass measuring 25 cm in its maximal dimension. Histology revealed an SEC, featuring foci of typical endometrioid carcinoma and areas of clear cell differentiation. This particular type of ovarian neoplasm, already described in 21 reported cases in the literature, must be distinguished from Sertoli cell tumours and Sertoli-Leydig cell tumours which are encountered at a younger age. We discuss the elements of the differential diagnosis and insist upon the value of anti-epithelial membrane antigen in identifying an SEC.
C1 NATL INST HLTH,BETHESDA,MD.
RP REMADI, S (reprint author), HOP CANTONAL UNIV GENEVA,INST CLIN PATHOL,1 RUE MICHEL SERVET,CH-1211 GENEVA,SWITZERLAND.
NR 8
TC 9
Z9 10
U1 0
U2 0
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch. Int. J. Pathol.
PD JUN
PY 1995
VL 426
IS 5
BP 533
EP 536
PG 4
WC Pathology
SC Pathology
GA RL401
UT WOS:A1995RL40100016
PM 7633665
ER

PT J
AU CIMINALE, V
   DAGOSTINO, DM
   ZOTTI, L
   FRANCHINI, G
   FELBER, BK
   CHIECOBIANCHI, L
AF CIMINALE, V
   DAGOSTINO, DM
   ZOTTI, L
   FRANCHINI, G
   FELBER, BK
   CHIECOBIANCHI, L
TI EXPRESSION AND CHARACTERIZATION OF PROTEINS PRODUCED BY MESSENGER-RNAS
   SPLICED INTO THE X-REGION OF THE HUMAN T-CELL LEUKEMIA LYMPHOTROPIC
   VIRUS TYPE-II
SO VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; OPEN READING
   FRAME; PX MESSENGER-RNA; HTLV-II; GENE-EXPRESSION; REV PROTEIN;
   IDENTIFICATION; TRANSFORMATION; INVIVO
AB In previous studies we showed that human T-cell leukemia/lymphotropic virus type I (HTLV-I) may produce novel proteins encoded in the X region. To investigate a possible correlation between expression of viral genes and different biologic properties of HTLV-I and HTLV-II, we analyzed expression of HTLV-II in the chronically infected cell line MoT. Reverse transcription-polymerase chain reaction analyses revealed that the virus produces several mRNAs singly or doubly spliced into the X region. Corresponding cDNAs were cloned and transfected into a HeLa cell line; resulting proteins were designated according to their sizes and coding open reading frames (ORFs). p10(xI) and p11(xV) were produced by a dicistronic doubly spliced mRNA. p10(xI) was generated by translation of the first exon of rex linked to the x-I ORF; p11(xV) was translated from the tax initiation codon linked to the x-V ORF. Two singly spliced polycistronic mRNAs produced p28(xII), coded by the x-ll ORF, and several isoforms generated by initiation within the x-lll ORF. Studies of the proteins' subcellular localization revealed that they exhibited distinct targeting patterns. Comparison of these proteins with their HTLV-I counterparts indicated intriguing differences between these two viruses, suggesting that further study of the X region products may aid in defining genetic determinants of pathogenicity. (C) 1995 Academic Press, Inc.
C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892.
   NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD.
RP CIMINALE, V (reprint author), UNIV PADUA,IST ONCOL,VIA GATTAMELATA 64,I-35128 PADUA,ITALY.
FU NCI NIH HHS [N01-CO-4600, 1F 32CA60403-01]
NR 58
TC 54
Z9 55
U1 0
U2 0
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 1
PY 1995
VL 209
IS 2
BP 445
EP 456
DI 10.1006/viro.1995.1277
PG 12
WC Virology
SC Virology
GA RC351
UT WOS:A1995RC35100019
PM 7539968
ER

PT J
AU FONG, SE
   PALLANSCH, LA
   MIKOVITS, JA
   LACKMANSMITH, CS
   RUSCETTI, FW
   GONDA, MA
AF FONG, SE
   PALLANSCH, LA
   MIKOVITS, JA
   LACKMANSMITH, CS
   RUSCETTI, FW
   GONDA, MA
TI CIS-ACTING REGULATORY ELEMENTS IN THE BOVINE IMMUNODEFICIENCY VIRUS LONG
   TERMINAL REPEAT
SO VIROLOGY
LA English
DT Article
ID INFECTIOUS-ANEMIA VIRUS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; TAT
   GENE; NUCLEOTIDE-SEQUENCE; FUNCTIONAL DOMAINS; CELLULAR PROTEIN;
   TRANS-ACTIVATION; VISNA VIRUS; HIV-1 LTR
AB Functional cis-acting regulatory elements in the bovine immunodeficiency virus (BIV) long terminal repeat (LTR) were identified by deletion mapping and nuclear protein gel shift analysis using three BIV-infectible cell lines, Cf2Th, BLAC-20, and EREp. Deletion mapping studies indicated that putative NF-kappa B, GRE, AP-4, AP-1, CAAT, and ATF/CRE transcription factor elements positively contribute to LTR-directed gene expression in each cell line both in the presence and absence of the viral transactivator Tat Spl and overlapping AP-3 and retroviral core enhancer elements had variable effects on LTR-directed gene expression depending on cell type and presence or absence of Tat. In addition, a sequence spanning the LTR U5 region and the untranslated viral leader was strongly repressive in all cell lines. Tat transactivated the LTR 25-fold over basal levels in a TAR-dependent manner in Cf2Th cells. In contrast, Tat transactivated the LTR only 2.5-fold over basal levels in EREp and BLAC-20 cells in a TAR-independent manner. Probes for putative NF-kappa B, GRE, Spl, AP-4, AP-1, overlapping AP-3 and retroviral core enhancer, and juxtaposed CAAT and ATF-CRE elements specifically bound nuclear proteins from these three cell lines and HeLa cells, with the stoichiometry of binding being cell-type dependent. Probes for AP-4, AP-1, and juxtaposed CAAT and ATF/CRE elements exhibited greater protein binding with extracts from virally infected cells than with extracts from uninfected cells, suggesting that viral infection can modulate nuclear factor binding. The present studies indicate that several transcription factor elements in the BIV LTR have functional roles and that cell type can strongly determine the role they play in gene expression.
C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702.
NR 62
TC 10
Z9 10
U1 0
U2 0
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 1
PY 1995
VL 209
IS 2
BP 604
EP 614
DI 10.1006/viro.1995.1292
PG 11
WC Virology
SC Virology
GA RC351
UT WOS:A1995RC35100034
PM 7778292
ER

PT J
AU LAPPE, M
   RAUSCHECKER, JP
AF LAPPE, M
   RAUSCHECKER, JP
TI AN ILLUSORY TRANSFORMATION IN A MODEL OF OPTIC FLOW PROCESSING
SO VISION RESEARCH
LA English
DT Article
DE OPTIC FLOW; ILLUSION; EGOMOTION; MODELING
ID SUPRASYLVIAN VISUAL-CORTEX; RESPONSE SELECTIVITY; GUIDED NAVIGATION;
   NEURAL NETWORK; MACAQUE MONKEY; FIELD STIMULI; EYE-MOVEMENTS; IMAGE
   MOTION; MST NEURONS; SELF-MOTION
AB We present results from computer simulations of a biologically plausible model of heading detection in the visual motion pathway of higher mammals. These simulations are closely related to a recently discovered visual illusion in optic flow processing in humans. The model reproduces the results described for humans and suggests a possible explanation, namely that humans interpret the illusory stimuli in terms of egomotion. It provides further indication that the visual system makes use of visual information to cope with eye movement effects in dealing with optic flaw.
C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892.
RP LAPPE, M (reprint author), RUHR UNIV BOCHUM,DEPT ZOOL & NEUROBIOL,BOCHUM,GERMANY.
RI Rauschecker, Josef/A-4120-2013
NR 47
TC 25
Z9 25
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD JUN
PY 1995
VL 35
IS 11
BP 1619
EP 1631
DI 10.1016/0042-6989(94)00220-G
PG 13
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA QZ396
UT WOS:A1995QZ39600010
PM 7667919
ER

PT J
AU VARRICCHIO, CG
AF VARRICCHIO, CG
TI ISSUES TO CONSIDER WHEN PLANNING CANCER CONTROL INTERVENTIONS FOR WOMEN
SO WOMENS HEALTH ISSUES
LA English
DT Article; Proceedings Paper
CT Vision Conference - Womens Health in the Pacific Basin
CY SEP, 1994
CL MANOA, HI
ID PERSPECTIVE
AB This paper addresses the topic of cancer control for women in the Pacific Basin. Cancer control is defined and a brief overview of the incidence of breast, cervical, and uterine cancers and overall cancer rates for women in various Pacific Basin countries, compared with the incidence for these groups in Hawaii and in Los Angeles County, is presented. This information provides a frame of reference for discussion of issues related to cancer prevention, early detection/screening efforts, and symptom control in culturally diverse groups.
RP VARRICCHIO, CG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA.
NR 24
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 1049-3867
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD SUM
PY 1995
VL 5
IS 2
BP 64
EP 72
DI 10.1016/1049-3867(95)00026-Z
PG 9
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA RZ809
UT WOS:A1995RZ80900004
PM 7613110
ER

PT J
AU BEEBE, LE
   FORNWALD, LW
   RIGGS, CW
   ANDERSON, LM
AF BEEBE, LE
   FORNWALD, LW
   RIGGS, CW
   ANDERSON, LM
TI SUPPRESSION OF PULMONARY P4502B AND INDUCTION OF HEPATIC, INTESTINAL AND
   KIDNEY P4501A-1 AND P4501A-2 IN THE AH-RESPONSIVE AND NONRESPONSIVE
   MOUSE BY AROCLOR-1254
SO XENOBIOTICA
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS; LIVER-TUMORS; LUNG; RAT; CYTOCHROME-P-450;
   DEALKYLATION; P-450; IIB1
AB 1. Investigations in our laboratory have demonstrated a rapid suppression of the P4502b isoform in mouse lung, concomitant with significant induction of this enzyme in liver from these same animals. The current study was designed to determine whether the suppression by polychlorinated biphenyls of pulmonary P4502b required the presence of a functional Ah receptor, and additionally to delineate the time course of the induction responses to Aroclor 1254 in the liver, kidney, and intestine of the AH-responsive and non-responsive mouse.
   2. P450s were quantified by specific enzyme assay and immunoblot in liver (1a-1, 1a-2, 2b), lung (1a-1, 1a-2), kidney (1a-1, 1a-2, 2b) and small intestine (1a-1, 2b) of C57 and DBA animals at varying times (48 h-12 weeks) following a single intraperitoneal dose of Aroclor 1254 (250 mg/kg).
   3. The suppression of constitutive P4502b in the lung by Aroclor was observed in both strains, but was more prominent over a longer time course in the non-responsive animals. P4502b enzyme activity was increased in the liver and intestine of both strains of mouse; however, there was a significantly greater response to Aroclor in the C57 animals. These data indicate that the AH receptor does not participate in the suppression of pulmonary P4502b, and suggests that the regulation of inducible P4502b in liver and intestine is quantitatively different between these two strains of mouse.
   4. P4501a was predictably induced in all tissues examined from the C57 animal, but was largely unaffected by PCBs in the DBA strain. P4501a-2, which is also regulated by the Ah receptor, was highly induced in the liver of the responsive strain, and also increased approximately two-fold in the liver of the non-responsive animals. Kidney P1501a-2 was also modestly increased by Aroclor, only in the responsive mouse.
C1 FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702.
RP BEEBE, LE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA.
NR 21
TC 3
Z9 3
U1 2
U2 2
PU TAYLOR & FRANCIS LTD LONDON
PI LONDON
PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD JUN
PY 1995
VL 25
IS 6
BP 541
EP 551
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA RL164
UT WOS:A1995RL16400001
PM 7483655
ER

PT J
AU COPPOLA, R
   MYSLOBODSKY, M
   WEINBERGER, DR
AF COPPOLA, R
   MYSLOBODSKY, M
   WEINBERGER, DR
TI MIDLINE ABNORMALITIES AND PSYCHOPATHOLOGY - HOW RELIABLE IS THE
   MIDSAGITTAL MAGNETIC-RESONANCE WINDOW INTO THE BRAIN
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE MAGNETIC RESONANCE IMAGING; MIDSAGITTAL CUT; FRONTAL LOBE ATROPHY;
   CORPUS CALLOSUM; VERMAL ATROPHY
ID HUMAN CORPUS-CALLOSUM; POSTERIOR-FOSSA STRUCTURES; SEX-RELATED
   DIFFERENCES; NORMAL INDIVIDUALS; 4TH VENTRICLE; IMAGING MRI;
   SCHIZOPHRENIA; AUTISM; MORPHOLOGY; THICKNESS
AB The argument is made that mensuration of midsagittal magnetic resonance (MR) images is plagued with methodological errors due to confusion of the midsagittal MR image and the mesial brain surface. Several examples are given to demonstrate the effects of slice thickness and orientation on the size and shape of mesial structures. The benefits of examining contiguous slices and the necessity of consulting coronal and transaxial cuts in mensuration efforts of midsagittal cuts are emphasized.
C1 TEL AVIV UNIV,PSYCHOBIOL RES UNIT,IL-69978 RAMAT AVIV,ISRAEL.
RP COPPOLA, R (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA.
NR 40
TC 10
Z9 10
U1 1
U2 1
PU ELSEVIER SCI PUBL IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD MAY 31
PY 1995
VL 61
IS 1
BP 33
EP 42
DI 10.1016/0925-4927(95)02522-Y
PG 10
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA RF466
UT WOS:A1995RF46600004
PM 7568567
ER

PT J
AU RUTTIMANN, UE
   ANDREASON, PJ
   RIO, D
AF RUTTIMANN, UE
   ANDREASON, PJ
   RIO, D
TI HEAD MOTION DURING POSITRON EMISSION TOMOGRAPHY - IS IT SIGNIFICANT
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE FUNCTIONAL IMAGING; PET METHODOLOGY; FACE MASK RESTRAINT; CEREBRAL
   GLUCOSE UTILIZATION
ID BRAIN
AB High sensitivity for detecting local brain function differences from subsequent PET-images acquired at different cerebral stimulation states requires interscan head motion to be minimized. This motion was measured by an optical lever system during scanning (130 min) of 15 subjects in a dual-dose injection study. Despite motion restriction by a face-mask restraint system, rotations in the sagittal and coronal planes (up to 4.1 degrees and 2.4 degrees, respectively) significantly influenced the measured means and variances of local metabolic differences between states. Hence, adjustments for head movement by retrospective, digital slice realignment or, better, real-time corrections are important.
RP RUTTIMANN, UE (reprint author), NIAAA,CLIN STUDIES LAB,10 CTR DR MSC 1256,BETHESDA,MD 20892, USA.
NR 13
TC 22
Z9 22
U1 1
U2 1
PU ELSEVIER SCI PUBL IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD MAY 31
PY 1995
VL 61
IS 1
BP 43
EP 51
DI 10.1016/0925-4927(95)02565-F
PG 9
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA RF466
UT WOS:A1995RF46600005
PM 7568568
ER

PT J
AU JONES, JP
   SHOU, MG
   KORZEKWA, KR
AF JONES, JP
   SHOU, MG
   KORZEKWA, KR
TI STEREOSPECIFIC ACTIVATION OF THE PROCARCINOGEN BENZO[ALPHA]PYRENE - A
   PROBE FOR THE ACTIVE-SITES OF THE CYTOCHROME-P450 SUPERFAMILY
SO BIOCHEMISTRY
LA English
DT Article
ID AROMATIC-HYDROCARBONS; EPOXIDE HYDROLASE; CRYSTAL-STRUCTURE;
   DIOL-EPOXIDES; AMINO-ACID; METABOLISM; HYDROXYLATION; EXPRESSION
AB It has been established previously that the stereochemistry of epoxidation of the procarcinogen benzo[a]pyrene determines the potency of the ultimate carcinogen. Herein we report that seven human P450s, five rodent P450s, and two bacterial P450s all convert B[a]P to the most potent carcinogenic stereoisomer. This is in contrast to most P450-catalyzed reactions, for which the various P450 enzymes often differ in both regioselectivity and stereoselectivity. This is likely due to the large size of the substrate molecule and its constraints in the active sites. Smaller substrates that can rotate more freely in the active site may be expected to have greater variations in binding orientations and therefore greater differences in stereoselectivities. Molecular mechanics is used to determine the specific amino acids responsible for the stereochemical outcome. Molecular dynamics is then used to strengthen the hypothesis that a single helical region, one that is likely to be conserved in all P450s, plays a primary role in determining the stereoselectivity of the reaction.
C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892.
   UNIV PITTSBURGH,MED CTR,CTR CLIN PHARMACOL,PITTSBURGH,PA 15217.
RP JONES, JP (reprint author), UNIV ROCHESTER,DEPT PHARMACOL,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA.
FU NIEHS NIH HHS [ES06062]
NR 26
TC 25
Z9 25
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA PO BOX 57136, WASHINGTON, DC 20037-0136
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 30
PY 1995
VL 34
IS 21
BP 6956
EP 6961
DI 10.1021/bi00021a007
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RA976
UT WOS:A1995RA97600007
PM 7766605
ER

PT J
AU SACKETT, DL
AF SACKETT, DL
TI VINCA SITE AGENTS INDUCE STRUCTURAL-CHANGES IN TUBULIN DIFFERENT FROM
   AND ANTAGONISTIC TO CHANGES INDUCED BY COLCHICINE SITE AGENTS
SO BIOCHEMISTRY
LA English
DT Article
ID CALF BRAIN TUBULIN; NATURAL-PRODUCTS; BETA-TUBULIN; MAYTANSINE-BINDING;
   VINBLASTINE; RHIZOXIN; MICROTUBULE; PROTEIN; PODOPHYLLOTOXIN; ALKALOIDS
AB Vinca site agents are antimicrotubule compounds that bind to the same site on tubulin as do the vinca alkaloids. These include agents that induce the formation of nonmicrotubule oligomers of tubulin (vinblastine and vincristine) and agents that do not (maytansine and rhizoxin). All of these quench the fluorescence of tubulin upon binding. Quenching preferentially affects the red side of tubulin emission, Likely affecting more than one solvent-exposed tryptophan. Similar quenching is observed upon binding to either tubulin or tubulin-colchicine. None of these agents induces the local unfolding of the amphipathic helix in the carboxyl terminal region of beta-tubulin that colchicine and other colchicine site ligands do. Ah four vinca site agents inhibit this unfolding in tubulin-colchicine complexes without displacing colchicine. Both groups of vinca site agents enhance the chymotryptic cleavage of beta-tubulin after Tyr-281. Both groups of vinca site agents increase the beta-tubulin specificity of photolabeling with colchicine, and both groups inhibit colchicine-stimulated GTP hydrolysis. All of these effects common to both groups of vinca site agents are interpreted as due to vinca site occupancy alone. The vinca alkaloids differ from maytansine and rhizoxin by causing a large enhancement of chymotryptic cleavage of beta and a large inhibition of typtic cleavage of alpha, after Arg-339. These effects are interpreted as due to vinca induced oligomerization of tubulin. It is argued that the common binding site for the vinca site agents is located on beta-tubulin, close to the helix that is disrupted by colchicine.
RP SACKETT, DL (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 2A23,BETHESDA,MD 20892, USA.
NR 47
TC 41
Z9 44
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 MAY 30
PY 1995
VL 34
IS 21
BP 7010
EP 7019
DI 10.1021/bi00021a012
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RA976
UT WOS:A1995RA97600012
PM 7766610
ER

PT J
AU HOWARD, FB
   MILES, HT
   ROSS, PD
AF HOWARD, FB
   MILES, HT
   ROSS, PD
TI THE POLY(DT)CENTER-DOT-2POLY(DA) TRIPLE-HELIX
SO BIOCHEMISTRY
LA English
DT Article
ID DNA; EQUILIBRIA; ACIDS
AB A new homopolynucleotide triple helix, (dT)(n) . 2(dA)(n), detected by circular dichroism mixing curves, is the product of an endothermic reaction of (dA)(n) .(dT)(n) with (dA)(n) at moderate temperatures and high salt concentrations ([NaCl] greater than or equal to 2.6 M): (dA)(n) .(dT)(n) + (dA)(n) reversible arrow (dT)(n) . 2(dA)(n). At higher temperatures (dT)(n) . 2(dA)(n) forms from the (dA)(n) .(dT)(n) duplex alone: 3[(dA)(n) .(dT)(n)] reversible arrow (dT)(n) . 2(dA)(n) + (dA)(n) . 2(dT)(n). Upon further heating, (dT)(n) . 2(dA)(n) is converted to the triplex (dA)(n) . 2(dT)(n): 2[(dT)(n) . 2(dA)(n)] reversible arrow (dA)(n) . 2(dT)(n) + 3(dA)(n). (dT)(n) . 2(dA)(n) forms owing to a favorable entropy change; Delta H-m is unfavorable, ranging from 1 to 2.5 kcal mol(-1), depending upon [NaCl]. The formation reaction is associated with a negative change in heat capacity. (dT)(n) . 2(dA)(n) is an extremely weak complex with a free energy of stabilization, Delta G(o) less than or equal to 100 cal mol(-1). T-m values of ultraviolet, circular dichroism, and differential scanning calorimetry transition curves for the formation of (dT)(n) . 2(dA)(n) decrease with increasing [NaCl], reflecting, in part, the net uptake of cations. The values of (dT(m)/d ln a+)(Delta H-m/RT(m)2) can be accounted for in terms of the charge spacing and cylindrical dimensions of the polynucleotides. The ionic strength dependence of this quantity is consistent with interaction of anions with (dA(n)). High concentrations of the anions Cl-, Br-, and ClO4- decrease the stability of (dT)(n) . 2(dA)(n) according to the lyotropic series. The highly polarizable anion, ClO4-, entirely prevents the formation of (dT)(n) . 2(dA)(n). Phase diagrams of the (dA)(n),(dT)(n) system in solutions of NaCl, NaBr, and NaClO4 are presented. A bonding scheme for (dT)(n) . 2(dA)(n) is proposed, and implications of this work for Py . Pu . Pu triple helices are discussed.
RP HOWARD, FB (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA.
NR 27
TC 24
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 MAY 30
PY 1995
VL 34
IS 21
BP 7135
EP 7144
DI 10.1021/bi00021a027
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RA976
UT WOS:A1995RA97600027
PM 7766624
ER

PT J
AU TANIZAWA, A
   KOHN, KW
   KOHLHAGEN, G
   LETEURTRE, F
   POMMIER, Y
AF TANIZAWA, A
   KOHN, KW
   KOHLHAGEN, G
   LETEURTRE, F
   POMMIER, Y
TI DIFFERENTIAL STABILIZATION OF EUKARYOTIC DNA TOPOISOMERASE-I CLEAVABLE
   COMPLEXES BY CAMPTOTHECIN DERIVATIVES
SO BIOCHEMISTRY
LA English
DT Article
ID CARCINOMA HT-29 CELLS; ANTITUMOR-ACTIVITY; WHEAT-GERM; SV40 DNA;
   RELIGATION REACTIONS; REPLICATION FORKS; MAMMALIAN-CELLS; STRAND BREAKS;
   CYTO-TOXICITY; INDUCTION
AB Camptothecins belong to a group of anticancer agents with a specific mechanism of action: stabilization and trapping of eukaryotic DNA topoisomerase I (top1) cleavable complexes. Two water-soluble camptothecin derivatives are in clinical trial, and their anticancer activity appears promising: topotecan and CPT-11. The latter is hydrolyzed to its active metabolite, SN-38. We have previously reported that SN-38 is among the most cytotoxic camptothecin derivatives and that the cleavable complexes induced by SN-38 are more stable than those induced by CPT in human colon carcinoma cells [Tanizawa et al. (1994) J. Natl. Cancer Inst. 86, 836-842]. Top1 inhibition was further investigated by determining the salt-induced religation rates of top1-cleavable complexes in fragments from the top1 cDNA. Religation depended on both the local DNA base sequence and the drug structure. Cleavable complexes induced by SN-38 and 10,11-methylenedioxycamptothecin were markedly more stable (less rapidly reversible) than those induced by CPT, topotecan, and 9-aminocamptothecin. The stability of 10-hydroxycamptothecin-induced cleavable complexes was intermediate to those of CPT and SN-38, indicating that both the 10-hydroxy and the 7-ethyl group of SN-38 probably interact with the drug binding site of top1-cleavable complexes. A DNA oligonucleotide containing a single top1 cleavage site was also used to compare the camptothecin derivatives. The salt stability of drug-induced cleavable complexes in the top1 oligonucleotide was correlated with the drug potencies to induce top1 cleavage. Cell killing requires that trapped cleavable complexes be converted to DNA damage as a result of replication fork collision. Therefore, the persistence of cleavable complexes may have important implications for anticancer drug efficacy.
C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892.
NR 51
TC 110
Z9 112
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA PO BOX 57136, WASHINGTON, DC 20037-0136
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 30
PY 1995
VL 34
IS 21
BP 7200
EP 7206
DI 10.1021/bi00021a035
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RA976
UT WOS:A1995RA97600035
PM 7766631
ER

PT J
AU JIANG, XC
   BRUCE, C
   COCKE, T
   WANG, S
   BOGUSKI, M
   TALL, AR
AF JIANG, XC
   BRUCE, C
   COCKE, T
   WANG, S
   BOGUSKI, M
   TALL, AR
TI POINT MUTAGENESIS OF POSITIVELY CHARGED AMINO-ACIDS OF CHOLESTERYL ESTER
   TRANSFER PROTEIN - CONSERVED RESIDUES WITHIN THE LIPID TRANSFER
   LIPOPOLYSACCHARIDE-BINDING PROTEIN GENE FAMILY ESSENTIAL FOR FUNCTION
SO BIOCHEMISTRY
LA English
DT Article
ID NEUTRALIZING MONOCLONAL-ANTIBODY; PERMEABILITY-INCREASING PROTEIN;
   SCANNING MUTAGENESIS; PLASMA-LIPOPROTEINS; EXPRESSION; CLONING; EPITOPE;
   REGION; CDNA
AB The cholesteryl ester transfer protein (CETP) binds to plasma lipoproteins and transfers neutral lipids between them. Previous studies showed that Lipoprotein binding involves ionic interactions between CETP and lipoproteins, with increased binding of CETP to lipoproteins carrying increased negative charge. In order to understand the molecular determinants of Lipoprotein binding in CETP, site-directed mutagenesis was carried out on positively charged amino acids within and outside regions of conserved sequence in the putative family of lipid transfer/lipopolysaccharide (LPS) binding proteins (LT/LBP). Within the conserved regions, two mutant proteins, K233A and R259D, were well secreted by the transfected cells but showed markedly reduced cholesteryl ester transfer activity. Separating the bound from free CETP by gel filtration after incubation with HDL, HDL binding by K233A was found to be impaired, suggesting that the binding deficiency of the mutant may be responsible for decreased transfer activity. Kinetic analysis showed a marked increase in the apparent K-m but no change in V-max, consistent with a lipoprotein binding defect. Thus, within CETP, K233 and R259 play an essential role in cholesteryl ester transfer activity probably by mediating binding of CETP to lipoproteins. Sequence alignment of CETP, phospholipid transfer protein, LPS binding protein, and bactericidal permeability-inducing protein showed that K223 and R259 were strictly conserved as positively charged amino acids, suggesting a common function within the LT/LBP gene family.
C1 COLUMBIA UNIV,DEPT MED,DIV MOLEC MED,NEW YORK,NY 10032.
   NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894.
FU NHLBI NIH HHS [HL22682]
NR 34
TC 30
Z9 30
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 MAY 30
PY 1995
VL 34
IS 21
BP 7258
EP 7263
DI 10.1021/bi00021a042
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RA976
UT WOS:A1995RA97600042
PM 7766637
ER

PT J
AU JUBERT, AH
   CASTRO, EA
   OTTAVIANELLI, E
   CACHAU, R
AF JUBERT, AH
   CASTRO, EA
   OTTAVIANELLI, E
   CACHAU, R
TI THEORETICAL-STUDY OF THE PHOTOCHEMICAL DECOMPOSITION OF CF3COF
SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE
LA English
DT Article; Proceedings Paper
CT VIIth Brazilian Symposium of Theoretical Chemistry
CY NOV 21-24, 1993
CL CAXAMBU, BRAZIL
ID SURFACE CROSSINGS
AB The molecular structure and the potential energy surface of the low lying states of CF3 COF are examined using the ah initio method. The C-F bond cleavage reaction, involving a carbon atom double bonded to an oxygen atom (carrying an n lone pair) and a fluorine atom cr to it, is also studied. The state correlation diagrams for this reaction are calculated. The main features of these diagrams and their relevance to the reaction mechanism studies are discussed.
C1 UNIV NACL SALTA,FAC CIENCIAS EXACTAS,DEPT QUIM,RA-4400 SALTA,ARGENTINA.
   NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM LAB,FREDERICK,MD 21702.
RP JUBERT, AH (reprint author), NATL UNIV LA PLATA,FAC CIENCIAS EXACTAS,DEPT QUIM,QUINOR,CALLE 47 & 115,CC 962,RA-1900 LA PLATA,ARGENTINA.
NR 11
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-1280
J9 THEOCHEM-J MOL STRUC
JI Theochem-J. Mol. Struct.
PD MAY 30
PY 1995
VL 335
BP 97
EP 105
PG 9
WC Chemistry, Physical
SC Chemistry
GA RE187
UT WOS:A1995RE18700014
ER

PT J
AU LUO, YQ
   HIRASHIMA, N
   LI, YH
   ALKON, DL
   SUNDERLAND, T
   ETCHEBERRIGARAY, R
   WOLOZIN, B
AF LUO, YQ
   HIRASHIMA, N
   LI, YH
   ALKON, DL
   SUNDERLAND, T
   ETCHEBERRIGARAY, R
   WOLOZIN, B
TI PHYSIOLOGICAL LEVELS OF BETA-AMYLOID INCREASE TYROSINE PHOSPHORYLATION
   AND CYTOSOLIC CALCIUM
SO BRAIN RESEARCH
LA English
DT Article
DE AMYLOID PRECURSOR PROTEIN; MATRIX PROTEIN; SIGNAL TRANSDUCTION; PC-12
   CELL; OLFACTORY NEUROBLAST; ALZHEIMERS DISEASE; NGF
ID NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; BILAYER-MEMBRANES;
   CELL-ADHESION; PROTEIN; RECEPTOR; PRECURSOR; PEPTIDE; NEURONS;
   NEUROTOXICITY
AB The a beta peptide is a neurotoxic peptide that accumulates in the brains of Alzheimer patients, but is also present in body fluids at subnanomolar levels. The potential effects of these low levels of a beta are unclear. We now show that one such action is to increase tyrosine phosphorylation in PC12 cells and olfactory neuroblasts. Application of a beta(25-35) or a beta(1-40) induces a dose-dependent increase in the tyrosine phosphorylation in both whole cells and in vitro. The increase in tyrosine phosphorylation is both rapid and sensitive, being stimulated by picomolar doses of a beta and occurring within 1 min of application. Calcium imaging experiments provide further support for the role of tyrosine phosphorylation in the action of a beta. While a beta does not alter calcium metabolism under basal conditions, the addition of a beta induces a rapid increase in cytoplasmic calcium in olfactory neuroblasts that have been treated with the tyrosine phosphatase inhibitor, sodium orthovanadate or in PC12 cells treated with nerve growth factor. These responses could be blocked by the tyrosine kinase inhibitor, herbimycin. These calcium responses displayed an obligate requirement for the presence of matrix proteins. The identification of a rapid, sensitive assay for the action of a beta may facilitate investigations of its mechanism of action.
C1 NIMH,GERIATR PSYCHIAT SERV,BETHESDA,MD 20892.
   NINCDS,ADAPT SYST LAB,BETHESDA,MD 20892.
NR 33
TC 49
Z9 51
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 MAY 29
PY 1995
VL 681
IS 1-2
BP 65
EP 74
DI 10.1016/0006-8993(95)00282-U
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA RD895
UT WOS:A1995RD89500008
PM 7552293
ER

PT J
AU HAVER, E
   LICHTSTEIN, D
   MUNSON, PJ
AF HAVER, E
   LICHTSTEIN, D
   MUNSON, PJ
TI MULTIPLE TYPES OF BINDING-SITES FOR ATRIAL-NATRIURETIC-PEPTIDE IN RAT
   OLFACTORY-BULB MEMBRANES AND SYNAPTOSOMES
SO BRAIN RESEARCH
LA English
DT Article
DE ATRIAL NATRIURETIC PEPTIDE; OLFACTORY BULB; SYNAPTOSOME; RECEPTOR
ID COMPUTERIZED OPTIMIZATION; EXPERIMENTAL-DESIGN; BRAIN SYNAPTOSOMES;
   CROSS-LINKING; ESTIMATING KD; RECEPTORS; LIGAND; PURIFICATION; RELEASE;
   TISSUES
AB The binding of atrial natriuretic peptide (ANP) to rat olfactory bulb membranes and synaptosomes was examined. [I-125]ANP (rat, 99-126) bound specifically to a single class of binding site on olfactory bulb membrane preparation with dissociation constant (K-d) of 106 pM and maximum binding capacity (B-max) of 13.6 fmol/mg protein. Comparable results were obtained when the binding was characterized using displacement and kinetic experiments. The ring deleted analog of ANP, C-ANP (rat, 4-23) displaced [I-125]ANP only minimally from its binding site in the membrane preparation. Saturation, displacement and blocking experiments on [I-125]ANP binding to rat olfactory bulb synaptosomes revealed the presence of two distinct binding sites. Simultaneous analysis of homogeneous and heterogeneous displacement curves and blocking experiments revealed the quantitative characteristics of these receptors to be: K-d1 = 44 pM, B-max1 = 42 fmol/mg protein and K-d2 = 1050 pM, B-max2 = 173 fmol/mg protein, for the high and low affinity binding sites, respectively. Kinetic experiments further confirmed the differences between the receptors present in the membranes and the synaptosomes preparations. The demonstration of multiple ANP binding sites in olfactory bulb synaptosomes but not membrane preparations raises the possibility of a particular function of ANP in nerve terminals.
C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT PHYSIOL,IL-91120 JERUSALEM,ISRAEL.
   NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,ANALYT BIOL SECT,BETHESDA,MD 20892.
NR 42
TC 3
Z9 3
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 MAY 29
PY 1995
VL 681
IS 1-2
BP 75
EP 83
DI 10.1016/0006-8993(95)00287-Z
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA RD895
UT WOS:A1995RD89500009
PM 7552294
ER

PT J
AU NOMIZU, M
   WEEKS, BS
   WESTON, CA
   KIM, WH
   KLEINMAN, HK
   YAMADA, Y
AF NOMIZU, M
   WEEKS, BS
   WESTON, CA
   KIM, WH
   KLEINMAN, HK
   YAMADA, Y
TI STRUCTURE-ACTIVITY STUDY OF A LAMININ ALPHA-1 CHAIN ACTIVE PEPTIDE
   SEGMENT ILE-LYS-VAL-ALA-VAL (IKVAV)
SO FEBS LETTERS
LA English
DT Article
DE LAMININ; IKVAV; SYNTHETIC PEPTIDE; D-AMINO ACID; CELL ATTACHMENT;
   NEURITE OUTGROWTH
ID AMINO-ACID-SEQUENCE; A-CHAIN; SYNTHETIC PEPTIDE; NEURITE OUTGROWTH;
   CELL-ADHESION; GLOBULAR DOMAIN; IDENTIFICATION; BINDING; SITE; PROTEIN
AB The IKVAV sequence, one of the most potent active sites of laminin-1, has been shown to promote cell adhesion, neurite outgrowth, and tumor growth, Here we have determined the structural requirements of the IKVAV sequence for cell attachment and neurite outgrowth using various 12-mer synthetic peptide analogs, All-L- and all-D-IKVAV peptides showed cell attachment and neurite outgrowth activities, In contrast, all-L- and all-D-reverse-sequence peptides were not active, Some of the analogs, in which the lysine and isoleucine residues of the IKVAV peptide were substituted with different amino acids, promoted cell attachment, but none of the analog peptides showed neurite outgrowth activity comparable to that of the IKVAV peptide, These results suggest that the lysine and isoleucine residues are critical for the biological functions of the IKVAV peptide.
C1 HAMILTON COLL,DEPT BIOL,CLINTON,NY 13323.
RP NOMIZU, M (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 427,BETHESDA,MD 20892, USA.
RI Kim, Wooho/G-3703-2011
NR 29
TC 55
Z9 55
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD MAY 29
PY 1995
VL 365
IS 2-3
BP 227
EP 231
DI 10.1016/0014-5793(95)00475-O
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA RB216
UT WOS:A1995RB21600028
PM 7781784
ER

PT J
AU MANDEL, JS
   MCLAUGHLIN, JK
   SCHLEHOFER, B
   MELLEMGAARD, A
   HELMERT, U
   LINDBLAD, P
   MCCREDIE, M
   ADAMI, HO
AF MANDEL, JS
   MCLAUGHLIN, JK
   SCHLEHOFER, B
   MELLEMGAARD, A
   HELMERT, U
   LINDBLAD, P
   MCCREDIE, M
   ADAMI, HO
TI INTERNATIONAL RENAL-CELL CANCER STUDY .4. OCCUPATION
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
ID RETROSPECTIVE COHORT MORTALITY; RISK-FACTORS; UNITED-STATES; WORKERS;
   CARCINOMA; ASBESTOS; CADMIUM; DEATH; CONSUMPTION; ASSOCIATION
AB The relationship between renal-cell cancer (RCC) and occupation was investigated in an international multicenter population-based case-control study. Study centers in Australia, Denmark, Germany, Sweden and the United States interviewed 1732 incident RCC cases and 2309 controls. Significant associations were found with employment in the blast-furnace or the coke-oven industry [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7], the iron and steel industry (RR, 1.6; 95% CI, 1.2-2.2) and exposure to asbestos(RR, 1.4; 95% CI, 1.1-1.8), cadmium (RR, 2.0; 95% CI, 1.0-3.9), dry-cleaning solvents (RR, 1.4; 95% CI, 1.1-1.7), gasoline (RR, 1.6; 95% CI, 1.2-2.0) and other petroleum produces(RR, 1.6; 95% CI, 1.3-2.1). Asbestos, petroleum products and dry-cleaning solvents appear to merit further investigation, in view of the relationship between risk and duration of employment or exposure and after adjustment for confounding. There was a negative association between RCC and education, but it was not consistent across all centers. Overall, the results of our multicenter case-control study suggest that occupation may be more important in the etiology of RCC than indicated by earlier studies. (C) 1995 Wiley-Liss, Inc.
C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892.
   GERMAN CANC RES CTR,DIV EPIDEMIOL,W-6900 HEIDELBERG,GERMANY.
   DANISH CANC SOC,DANISH CANC REGISTRY,COPENHAGEN,DENMARK.
   BREMEN INST PREVENT & SOCIAL MED,BREMEN,GERMANY.
   UNIV UPPSALA HOSP,UPPSALA,SWEDEN.
   NSW CANC COUNCIL,CANC EPIDEMIOL RES UNIT,SYDNEY,NSW,AUSTRALIA.
   UPPSALA UNIV,UPPSALA,SWEDEN.
RP MANDEL, JS (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT MED,420 DELAWARE ST SE,BOX 807 UMHC,MINNEAPOLIS,MN 55455, USA.
NR 38
TC 128
Z9 131
U1 2
U2 4
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 29
PY 1995
VL 61
IS 5
BP 601
EP 605
DI 10.1002/ijc.2910610503
PG 5
WC Oncology
SC Oncology
GA RB283
UT WOS:A1995RB28300002
PM 7768630
ER

PT J
AU ROBERTS, BJ
   SHOAF, SE
   SONG, BJ
AF ROBERTS, BJ
   SHOAF, SE
   SONG, BJ
TI RAPID CHANGES IN CYTOCHROME P4502E1 (CYP2E1) ACTIVITY AND OTHER P450
   ISOZYMES FOLLOWING ETHANOL WITHDRAWAL IN RATS
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE ETHANOL; WITHDRAWAL; CYP1A; CYP2E1; CYP2B1; CYP3A
ID PARA-NITROPHENOL HYDROXYLATION; ASSAY CONDITIONS; HIGH-FAT; LIVER;
   ENZYMES; DEGRADATION; MECHANISMS; INDUCTION; ALCOHOL; GENE
AB This study describes the effects of chronic ethanol (ETOH) treatment and withdrawal on the rat hepatic mixed-function mono-oxygenase system. Male Sprague-Dawley rats (150-200 g, 10 per group) were administered ETCH as part of the Lieber-deCarli liquid diet for 3 weeks. Ethanol was removed, and the animals were euthanized at 0, 24, 48, 72 and 168 hr post-withdrawal. Microsomes were prepared, and ethanol-inducible cytochrome P4502E1 (CYP2E1) activity was measured using the enzyme markers N-nitrosodimethylamine demethylase (NDMAd), p-nitrophenol hydroxylase (PNPH) and aniline hydroxylase (AH). Activities were found to be induced significantly after chronic ETOH feeding using all three assays (NDMAd, 5-fold; PNPH, 3.5-fold; AH, 9-fold). Upon ETOH withdrawal, all three activities dropped markedly, with NDMAd and PNPH at control values at 24 hr and all subsequent time points. AH activity remained 3-fold higher than controls at 24, 48 and 72 hr. Western blot analyses showed that immunoreactive CYP2E1 returned to control at 24 hr, consonant with NDMAd and PNPH activities. The prolonged induction of AH activity following ETOH withdrawal indicates that it is not a specific marker of CYP2E1-catalyzed reactions. Collectively, these data are suggestive of a rapid mechanism of CYP2E1 degradation in the rat liver. Of the other parameters investigated in this study, total cytochrome P450 content was increased 2.5-fold after ETOH feeding, with levels dropping markedly 24 hr post-withdrawal. NADPH-dependent cytochrome c reductase activity was unchanged throughout the course of the study. CYP1A1, CYP2B1 and CYP3A activities were assessed by the substrate probes ethoxyresorufin O-dealkylase (EROD), pentoxyresorufin O-dealkylase (PROD) and erythromycin N-demethylase (ERNd). EROD and PROD were induced significantly by ETCH administration (2-fold) at 0 hr, with EROD remaining elevated over controls 24 hr post-withdrawal. Quantitative western blot analysis of CYP1A1 and CYP2B1 revealed a pattern of immunostaining generally consistent with but less variable than levels predicted by the respective substrate markers. Both proteins were induced significantly by chronic ethanol administration (CYP1A1, 1.9-fold; CYP2B1, 4-fold). Induction of these P450 isoforms persisted for several days following withdrawal. In contrast, immunoreactive CYP1A2 was found to decrease significantly (by 30-40%) during ethanol withdrawal (24, 48, 72, 168 hr). ERNd activity was induced significantly by chronic ETOH feeding (2.5-fold) and remained so for 24 hr into the withdrawal period (2-fold). Immunoreactive CYP3A1 was also induced significantly following ETOH administration (0 hr) and 24 hr following withdrawal. Collectively, the data presented suggest that chronic ethanol feeding induces in vivo at least four distinct P450 isoforms: CYP2E1, CYP1A1, CYP2B1 and CYP3A1. Ethanol withdrawal resulted in a 30-40% loss of CYP1A2. CYP1A1, CYP2B1 and CYP3A1 were elevated during ethanol withdrawal, unlike CYP2E1, a protein that undergoes rapid degradation following tho removal of ethanol. Such findings are consistent with several distinct mechanisms of P450 isoform induction/degradation by ethanol.
C1 NIAAA,DICBR,NEUROGENET LAB,BETHESDA,MD 20892.
RP ROBERTS, BJ (reprint author), NIAAA,DICBR,CLIN STUDIES LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 3C103,BETHESDA,MD 20892, USA.
NR 42
TC 72
Z9 74
U1 1
U2 6
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 MAY 26
PY 1995
VL 49
IS 11
BP 1665
EP 1673
DI 10.1016/0006-2952(95)00098-K
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RB853
UT WOS:A1995RB85300016
PM 7786308
ER

PT J
AU PENNYPACKER, KR
   HUDSON, PM
   HONG, JS
   MCMILLIAN, MK
AF PENNYPACKER, KR
   HUDSON, PM
   HONG, JS
   MCMILLIAN, MK
TI DNA-BINDING ACTIVITY OF CREB TRANSCRIPTION FACTORS DURING ONTOGENY OF
   THE CENTRAL-NERVOUS-SYSTEM
SO DEVELOPMENTAL BRAIN RESEARCH
LA English
DT Article
DE CAMP RESPONSIVE ELEMENT; BRAIN; GENE REGULATION; AP-1 ELEMENT;
   FOS-RELATED ANTIGEN
ID CAMP-RESPONSE-ELEMENT; PROTEIN KINASE-A; ATF CDNA CLONES; CYCLIC-AMP;
   C-FOS; GENE-TRANSCRIPTION; MONOCYTIC DIFFERENTIATION; RAT STRIATUM;
   JUN-B; AP-1
AB During the early postnatal period, the rat brain contains high basal levels of AP-1 DNA binding activity which declines to the low levels found in the adult by the third postnatal week. Although the individual transcription factors that comprise this AP-1 DNA binding complex had not been identified, we discovered that these proteins were immunoreactive to the cAMP responsive element binding protein (CREB) and also recognized the CRE element. The 45 kDa CREB-immunoreactive protein was detected at high levels only during the first postnatal week. CRE and AP-1 DNA binding activities were studied in the olfactory bulb, striatum, hindbrain, hippocampus, hypothalamus and cerebellum. In general, the DNA binding activity correlated with the stage of maturation of the particular brain region. However, basal AP-1 DNA binding in the olfactory bulb from adults remained slightly elevated relative to other brain regions. Interestingly, the DNA binding complex in the olfactory bulb began to include fos-related antigen as well as CREB by the third postnatal week. The fra-containing complex only recognizes the AP-1 element, while the CREB complex can bind to either CRE or AP-1 sequences. Thus, there is crosstalk between the signal transduction systems that activate CREB and AP-1 transcription factors. This elevated CREB DNA binding activity may be a sensitive index for studying the development of the brain and could be involved in modulating the genomic program in differentiating cells.
C1 NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709.
RI Pennypacker, Keith/I-5092-2012
NR 49
TC 19
Z9 19
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-3806
J9 DEV BRAIN RES
JI Dev. Brain Res.
PD MAY 26
PY 1995
VL 86
IS 1-2
BP 242
EP 249
DI 10.1016/0165-3806(95)00033-A
PG 8
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA RC418
UT WOS:A1995RC41800024
ER

PT J
AU MOSS, J
   VAUGHAN, M
AF MOSS, J
   VAUGHAN, M
TI STRUCTURE AND FUNCTION OF ARF PROTEINS - ACTIVATORS OF CHOLERA-TOXIN AND
   CRITICAL COMPONENTS OF INTRACELLULAR VESICULAR TRANSPORT PROCESSES
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; BREFELDIN-A;
   GUANINE-NUCLEOTIDE; GOLGI MEMBRANES; VESICLES; CELLS; COATOMER;
   EXCHANGE; FUSION
RP MOSS, J (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892, USA.
NR 54
TC 251
Z9 255
U1 2
U2 7
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 MAY 26
PY 1995
VL 270
IS 21
BP 12327
EP 12330
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ711
UT WOS:A1995QZ71100001
PM 7759471
ER

PT J
AU CIPPITELLI, M
   SICA, A
   VIGGIANO, V
   YE, JP
   GHOSH, P
   BIRRER, MJ
   YOUNG, HA
AF CIPPITELLI, M
   SICA, A
   VIGGIANO, V
   YE, JP
   GHOSH, P
   BIRRER, MJ
   YOUNG, HA
TI NEGATIVE TRANSCRIPTIONAL REGULATION OF THE INTERFERON-GAMMA PROMOTER BY
   GLUCOCORTICOIDS AND DOMINANT-NEGATIVE MUTANTS OF C-JUN
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACTIVATED T-CELLS; DNA-BINDING; GENE-EXPRESSION; NUCLEAR FACTOR;
   LYMPHOCYTE-T; HUMAN INTERLEUKIN-2; SIGNALING PATHWAY; MAMMALIAN-CELLS;
   FAMILY MEMBERS; TATA BOX
AB Interferon-gamma (IFN-gamma) is an immunoregulatory cytokine expressed in large granular lymphocytes and T cells. However, the molecular mechanisms underlying IFN-gamma gene transcription have not been fully defined. Here, we analyze the mechanisms responsible for the inhibition of IFN-gamma promoter activity by the glucocorticoid hormone dexamethasone. Cotransfection assays performed in Jurkat T cells demonstrated that the activity of the initial 108 base pairs of the IFN-gamma promoter was down-regulated in the presence of dexamethasone. Furthermore, utilizing electrophoretic mobility shift analysis, we identified activator protein 1 AP-1-cAMP response element binding protein-activating transcription factor (CREB-ATF) binding elements situated in positions of the IFN-gamma promoter previously identified as essential for promoter activity. Moreover, dominant negative mutants of the c-Jun proto-oncogene were able to mimic the same down-regulatory effect exerted by dexamethasone, and mutations that abolished the binding of the AP-1 . CREB-ATF factors were able to block the glucocorticoid effect.
   These results suggest a model involving the inhibition of IFN-gamma AP-1 CREB-ATF DNA binding complexes as one of the mechanisms involved in the negative regulatory action of glucocorticoids on IFN-gamma gene expression and support the relevance of AP-1 . CREB-ATF binding factors during the transcriptional activation of the IFN-gamma promoter in T cells.
C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
   NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850.
OI CIPPITELLI, Marco/0000-0002-9620-538X
NR 65
TC 110
Z9 111
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 MAY 26
PY 1995
VL 270
IS 21
BP 12548
EP 12556
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ711
UT WOS:A1995QZ71100036
PM 7759501
ER

PT J
AU YOO, SH
AF YOO, SH
TI PH-INDUCED AND CA2+-INDUCED CONFORMATIONAL CHANGE AND AGGREGATION OF
   CHROMOGRANIN-B - COMPARISON WITH CHROMOGRANIN-A AND IMPLICATION IN
   SECRETORY VESICLE BIOGENESIS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHROMAFFIN GRANULES; SECRETOGRANIN-I; PROTEIN; BINDING; SEQUENCE; CA-2+;
   PHEOCHROMOCYTOMA; WIDESPREAD; ENDOCRINE; MEMBRANE
AB Chromogranins A and B have been known to undergo pH- and Ca2+-dependent aggregation, and this property is considered essential for the proper sorting of the vesicular matrix proteins. In the present study, purified native chromogranin B (CGB) from bovine adrenal medulla was used to study the pH- and Ca2+-dependent conformational changes and aggregation property. Similar to chromogranin A (CGA), which had been shown to undergo pH- and Ca2+-dependent conformational changes and to be composed of 60-65% random coil with 25-40% alpha-helicity, chromogranin B was also shown to consist of 65-70% random coil, 15-25% alpha-helix, and 10-15% beta-sheet structures. The high percentage of random coil suggests that CGB behaves hydrodynamically as an asymmetric molecule, thus explaining its anomalous migration on SDS-polyacrylamide gels. Further, CGB eluted from a gel filtration column in the volume indicative of a globular protein with molecular weight of similar to 200,000 at both the intravesicular pH of 5.5 and a near physiological pH of 7.5. Considering that dimeric CGA eluted from a gel filtration column in the position suggestive of a 300-kDa protein, this result indicated that CGB exists in a monomeric state at both pH levels. Like CGA, which exhibited greater aggregation at pH 5.5 than at pH 7.5 upon Ca2+ binding, CGB also aggregated much more readily at pH 5.5 than at pH 7.5. However, there was a marked difference in the aggregation properties of CGA and CGB with regard to their sensitivity to Ca2+: CGB was at least 2 orders of magnitude more sensitive to Ca2+ than CGA. This suggested that, in spite of the low concentration of CGB (approximately one-tenth that of CGA) in bovine adrenal chromaffin cells, CGB would start to aggregate well ahead of CGA in the trans-Golgi network. In view of the proposed importance of the pH- and Ca2+-induced chromogranin aggregation in vesicle biogenesis, the extreme sensitivity of CGB aggregation to Ca2+ appears to underline the potential importance of CGB aggregation in the early stages of vesicle biogenesis.
RP YOO, SH (reprint author), NIDCD, NEUROCHEM LAB, 5 RES COURT, 2A37, BETHESDA, MD 20892 USA.
NR 29
TC 40
Z9 40
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 MAY 26
PY 1995
VL 270
IS 21
BP 12578
EP 12583
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ711
UT WOS:A1995QZ71100040
PM 7759505
ER

PT J
AU WELCH, RW
   WANG, YH
   CROSSMAN, A
   PARK, JB
   KIRK, KL
   LEVINE, M
AF WELCH, RW
   WANG, YH
   CROSSMAN, A
   PARK, JB
   KIRK, KL
   LEVINE, M
TI ACCUMULATION OF VITAMIN-C (ASCORBATE) AND ITS OXIDIZED METABOLITE
   DEHYDROASCORBIC ACID OCCURS BY SEPARATE MECHANISMS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COULOMETRIC ELECTROCHEMICAL DETECTION; ADRENOMEDULLARY CHROMAFFIN CELLS;
   HUMAN-NEUTROPHILS; INSITU KINETICS; TRANSPORT; FIBROBLASTS; GLUCOSE;
   REDUCTASE; DISULFIDE; AFFINITY
AB It is unknown whether ascorbate alone (vitamin C), its oxidized metabolite dehydroascorbic acid alone, or both species are transported into human cells. This problem was addressed using specific assays for each compound, freshly synthesized pure dehydroascorbic acid, the specially synthesized analog 6-chloroascorbate, and a new assay for 6-chloroascorbate. Ascorbate and dehydroascorbic acid were transported and accumulated distinctly; neither competed with the other, Ascorbate was accumulated as ascorbate by sodium-dependent carrier-mediated active transport, Dehydroascorbic acid transport and accumulation as ascorbate was at least 10-fold faster than ascorbate transport and was sodium-independent. Once transported, dehydroascorbic acid was immediately reduced intracellularly to ascorbate. The analog 6-chloroascorbate had no effect on dehydroascorbic acid transport but was a competitive inhibitor of ascorbate transport. The K-i for 6-chloroascorbate (2.9-4.4 mu M) was similar to the K-m for ascorbate transport (9.8-12.6 mu M) 6-Chloroascorbate was itself transported and accumulated in fibroblasts by a sodium-dependent transporter. These data provide new information that ascorbate and dehydroascorbic acid are transported into human neutrophils and fibroblasts by two distinct mechanisms and that the compound available for intracellular utilization is ascorbate.
C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892.
   NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892.
NR 37
TC 151
Z9 155
U1 1
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 MAY 26
PY 1995
VL 270
IS 21
BP 12584
EP 12592
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ711
UT WOS:A1995QZ71100041
PM 7759506
ER

PT J
AU BARR, DP
   MASON, RP
AF BARR, DP
   MASON, RP
TI MECHANISM OF RADICAL PRODUCTION FROM THE REACTION OF CYTOCHROME-C WITH
   ORGANIC HYDROPEROXIDES - AN ESR SPIN-TRAPPING INVESTIGATION
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIPID-PEROXIDATION; OXIDATION; RESONANCE; PEROXYL; ALKOXYL; PROTEINS;
   CATALASE; HEMATIN; HEART
AB The mechanism for the reaction of cytochrome c with t-butyl hydroperoxide and cumene hydroperoxide was investigated, ESR spin trapping studies using 5,5-dimethyl-1-pyrroline N-oxide were performed to demonstrate the presence of hydroperoxide-derived peroxyl, alkoxyl, and methyl radicals. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide concentrations was used to determine the relative contributions of each radical adduct to each composite ESR spectrum, From these analyses, it was concluded that the alkoxyl radical of the hydroperoxide was the initial radical produced, presumably by homolytic scission of the O-O bond by ferric cytochrome c. This was in contrast to a previous ESR study that proposed a heterolytic peroxidase-type mechanism for the reaction of cytochrome c with organic hydroperoxides, Methyl radicals were produced from the beta-scission of the alkoxyl radical, The peroxyl radicals are shown to be secondary products formed from the reaction of oxygen with the methyl radical to produce the methyl peroxyl radical, In separate experiments, visible absorption spectroscopy revealed that the heme center was destroyed during the reaction, Both the heme destruction and production of radical adducts were inhibited by cyanide, presumably due to the formation of a cyanoheme complex.
RP BARR, DP (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA.
NR 35
TC 82
Z9 83
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 26
PY 1995
VL 270
IS 21
BP 12709
EP 12716
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ711
UT WOS:A1995QZ71100060
PM 7759524
ER

PT J
AU MURPHY, WJ
   RUI, H
   LONGO, DL
AF MURPHY, WJ
   RUI, H
   LONGO, DL
TI EFFECTS OF GROWTH-HORMONE AND PROLACTIN IMMUNE DEVELOPMENT AND FUNCTION
SO LIFE SCIENCES
LA English
DT Review
DE LYMPHOCYTE FUNCTION; NEUROENDOCRINE IMMUNE INTERACTIONS; IMMUNOGLOBULIN
ID LYMPHOCYTE-T PROLIFERATION; THYMIC EPITHELIAL-CELLS; FACTOR-I; DWARF
   MOUSE; TYROSINE KINASE; NEUROENDOCRINE HORMONES; IMMUNOLOGICAL CAPACITY;
   EXTRACELLULAR DOMAIN; IMMUNODEFICIENT MICE; BODY-COMPOSITION
AB Growth hormone and prolactin are neuroendocrine hormones that exert numerous effects on immune system function and development. Several fundamental questions are addressed in this review. Do neuroendocrine hormones affect specific immune cell types? What is the physiological significance of these effects? Can these effects be exploited clinically? While it is clear that there are indeed significant interactions between the neuroendocrine and immune systems, there ate relatively few examples with demonstrated physiological significance. Present studies indicate that growth hormone and prolactin may exert markedly different effects on immune cell types depending on their stage in differentiation. Recent emphasis has also been focussed on the use of these hormones or their antagonists clinically in the treatment of AIDS, cancer, and autoimmune disease states due to their pleiotropic effects and low toxicity after systemic administration. However, we do not yet have a clear picture of how the influence of neuroendocrine hormones may be used to favorably alter pathophysiologic processes affecting immune function and development.
C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702.
RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA.
NR 93
TC 76
Z9 85
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD MAY 26
PY 1995
VL 57
IS 1
BP 1
EP 14
DI 10.1016/0024-3205(95)00237-Z
PG 14
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA RA962
UT WOS:A1995RA96200001
PM 7596216
ER

PT J
AU EATON, WA
   HOFRICHTER, J
AF EATON, WA
   HOFRICHTER, J
TI THE BIOPHYSICS OF SICKLE-CELL HYDROXYUREA THERAPY
SO SCIENCE
LA English
DT Editorial Material
ID HEMOGLOBIN-S; DEOXYHEMOGLOBIN-S; CRYSTAL-STRUCTURE; GELATION;
   POLYMERIZATION; RESOLUTION; MECHANISM; KINETICS; DISEASE; FIBERS
RP EATON, WA (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA.
NR 25
TC 83
Z9 86
U1 1
U2 9
PU AMER ASSOC ADVAN SCIENCE
PI WASHINGTON
PA 1333 H ST NW, WASHINGTON, DC 20005
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 26
PY 1995
VL 268
IS 5214
BP 1142
EP 1143
DI 10.1126/science.7539154
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RA604
UT WOS:A1995RA60400026
PM 7539154
ER

PT J
AU WILCOX, AJ
   BAIRD, DD
   WEINBERG, CR
   HORNSBY, PP
   HERBST, AL
AF WILCOX, AJ
   BAIRD, DD
   WEINBERG, CR
   HORNSBY, PP
   HERBST, AL
TI FERTILITY IN MEN EXPOSED PRENATALLY TO DIETHYLSTILBESTROL
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GENITAL-TRACT; REPRODUCTIVE-TRACT; INUTERO; PREGNANCY; WOMEN;
   ADENOCARCINOMA; ASSOCIATION; UTERO; MICE
AB Background. Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men, However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol.
   Methods. In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility.
   Results. Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent), Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed). Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group. Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P=0.05). Men with genital malformations were nonetheless as fertile as other men. The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a woman, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner. Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido,
   Conclusions. High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero.
C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709.
   UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA.
   UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637.
RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA.
OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653
NR 28
TC 176
Z9 181
U1 1
U2 6
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 MAY 25
PY 1995
VL 332
IS 21
BP 1411
EP 1416
DI 10.1056/NEJM199505253322104
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA QY941
UT WOS:A1995QY94100004
PM 7723797
ER

PT J
AU REITMAN, M
   LEE, E
   WESTPHAL, H
AF REITMAN, M
   LEE, E
   WESTPHAL, H
TI FUNCTION OF THE UPSTREAM HYPERSENSITIVE SITES OF THE CHICKEN BETA-GLOBIN
   GENE-CLUSTER IN MICE
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID LOCUS ACTIVATION REGION; HUMAN ERYTHROID-CELLS; HUMAN GAMMA-GLOBIN;
   DEVELOPMENTAL REGULATION; TRANSGENIC MICE; EXPRESSION; CHROMATIN;
   DOMAIN; TRANSCRIPTION; INACTIVATION
AB We have shown previously that the chicken beta(A)-globin gene, with its 3' enhancer, is expressed in a copy number-dependent manner in transgenic mice. The expression level was low but increased similar to 6-fold upon inclusion of 11 kb of upstream DNA containing four DNase I hypersensitive sites. To study the effect of the individual upstream hypersensitive sites on transgene expression, we produced lines of mice in which the individual upstream sites were linked to the beta(A) gene and enhancer. RNA levels were measured in blood from adult animals. With each of these four constructs, the level of transgene RNA per DNA copy varied over a >20-fold range. These data suggest that addition of a hypersensitive site to the beta(A)-globin/enhancer region abrogates its position independent expression. The average beta(A)-globin expression per copy in the lines carrying an upstream site was comparable with that in lines without an upstream site. Thus, no single upstream hypersensitive site accounts for the higher level of beta(A)-globin expression seen in mice containing the complete upstream region. We had shown previously that control of the chicken beta-globin cluster is distributed between at least two regions, the beta(A)/epsilon enhancer and the upstream region. Our current results suggest that the control mediated by the upstream DNA is itself distributed and is not due to a single hypersensitive site.
C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892.
RP REITMAN, M (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA.
RI Reitman, Marc/B-4448-2013
OI Reitman, Marc/0000-0002-0426-9475
NR 41
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 25
PY 1995
VL 23
IS 10
BP 1790
EP 1794
DI 10.1093/nar/23.10.1790
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RC712
UT WOS:A1995RC71200021
PM 7784184
ER

PT J
AU SZEKELY, Z
AF SZEKELY, Z
TI A NEW APPROACH FOR AN HIV DOCKING-INHIBITOR DRUG DESIGNED ON THE BASIS
   OF THE DUAL RECOGNITION BINDING HYPOTHESIS BETWEEN THE CD4 RECEPTOR AND
   THE ENVELOPE GLYCOPROTEIN OF THE HIV
SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE
LA English
DT Article
DE CD4; DRUG DESIGN; GP120; HIV; HIV DOCKING-INHIBITOR; STRUCTURAL
   HYPOTHESIS
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GALACTOSYL CERAMIDE; CRYSTAL-STRUCTURE;
   ATOMIC-STRUCTURE; CELL-LINES; GP120; DELINEATION; DOMAINS; FRAGMENT;
   REGION
AB A structural hypothesis is presented in this paper for dual binding sites between the gp120 of HIV and the T-cell. One of the binding sites involved electrostatic attraction between positively charged sites (Lys(35), Lys(46) and Arg(59)) of the CD4 and the negatively charged sites (Asp(368), Glu(370) and Asp(457)) Of the gp120. It is suggested that the benzene ring of Phe(43) also acts as a lock at this site. The other site involves the galactose ending of one of the oligosaccharide antennas of the CD4 that docks close to one of the S-S linkages (perhaps at Cys(296)-S-S-Cys(331)) Of the gp120. It is suggested that the activated free OH at C4 position of the galactose acts as a nucleophile to break this strategically located S-S linkage. Such a structural alteration leads to a dramatic conformational change that may in fact trigger the fusion process. On the basis of this structural hypothesis a general glycopeptide structure is proposed that could act as a ''bivalent'' docking-inhibitor drug.
C1 UNIV TORONTO,DEPT CHEM,TORONTO,ON M5S 1A1,CANADA.
   ALBERT SZENT GYORGYI MED UNIV,DEPT MED CHEM,H-6720 SZEGED,HUNGARY.
RP SZEKELY, Z (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MSL,MOLEC ASPECTS DRUG DESIGN S,FREDERICK,MD 21702, USA.
NR 34
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-1280
J9 THEOCHEM-J MOL STRUC
JI Theochem-J. Mol. Struct.
PD MAY 25
PY 1995
VL 334
IS 2-3
BP 93
EP 100
PG 8
WC Chemistry, Physical
SC Chemistry
GA RD939
UT WOS:A1995RD93900001
ER

PT J
AU NEGRINI, C
   RIVOLTA, MN
   KALINEC, F
   KACHAR, B
AF NEGRINI, C
   RIVOLTA, MN
   KALINEC, F
   KACHAR, B
TI CLONING OF AN ORGAN OF CORTI ANION-EXCHANGER-2 ISOFORM WITH A TRUNCATED
   C-TERMINAL DOMAIN
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Note
DE ANION EXCHANGER; ALTERNATIVE SPLICING; AE2; (ORGAN OF CORTI)
ID PRE-MESSENGER RNA; CL-/HCO3 EXCHANGER; GENE-EXPRESSION; CDNA;
   ORGANIZATION; CELLS; SITE; AE3
AB We have isolated a cDNA clone from a guinea pig organ of Corti library encoding a new isoform of the Anion Exchanger 2 (AE2) protein, This cDNA clone shows an 83 bp deletion in the region that encodes the membrane domain of AE2. Analysis of the overlapping regions of genomic and cDNA clones indicates that the missing portion does not correspond exactly to a constitutive exon. The alternate splicing process that generates this transcript involves internal donor and acceptor sites which introduces a shift in the open reading frame. The resulting polypeptide has a conserved cytoplasmic N-terminal domain but the membrane C-terminal domain has only two of the fourteen membrane spanning regions. An affinity-purified antipeptide antibody to the novel C-terminus detects an 89 kDa polypeptide which agrees with the molecular mass predicted from the cDNA.
C1 NIDCD,CELLULAR BIOL LAB,ROCKVILLE,MD 20850.
   NIDCD,MOLEC GENET LAB,ROCKVILLE,MD 20850.
NR 17
TC 11
Z9 11
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD MAY 24
PY 1995
VL 1236
IS 1
BP 207
EP 211
DI 10.1016/0005-2736(95)00081-D
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA RC982
UT WOS:A1995RC98200027
PM 7794951
ER

PT J
AU ACRI, JB
   WONG, G
   WITKIN, JM
AF ACRI, JB
   WONG, G
   WITKIN, JM
TI STEREOSPECIFIC TRANSDUCTION OF BEHAVIORAL-EFFECTS VIA
   DIAZEPAM-INSENSITIVE GABA(A) RECEPTORS
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE BENZODIAZEPINE; GABA(A) RECEPTOR, DIAZEPAM-INSENSITIVE; DRUG
   DISCRIMINATION; BRETAZENIL; FLUMAZENIL; (RECEPTOR PARTIAL AGONIST); RO
   19-0528; GABA (GAMMA-AMINOBUTYRIC ACID); (PIGEON)
ID DISCRIMINATIVE STIMULUS PROPERTIES; AMINOBUTYRIC ACID(A) RECEPTOR;
   BENZODIAZEPINE RECEPTORS; RO 15-1788; ALCOHOL ANTAGONIST; H-3
   RO-15-4513; BINDING-SITES; RAT-BRAIN; LOCALIZATION; MIDAZOLAM
AB Previous studies reported a positive correlation between ligand affinities at diazepam-insensitive GABA(A) receptors and substitution for the discriminative stimulus effects of the benzodiazepine receptor antagonist, flumazenil, in pigeons. In the present experiments, bretazenil and Ro 14-5974 (ethyl-(S)-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]-pyrrolo-[2,1-c][1,4] benzodiazepine-1-carboxylate) partially substituted for, and blocked the discriminative stimulus effects of midazolam, congruent with their actions at diazepam-sensitive GABA, receptors in vitro. In addition, bretazenil and Ro 14-5974, but not their R-enantiomers, had high affinity for diazepam-insensitive receptors and fully substituted for the discriminative stimulus effects of flumazenil. The R-enantiomers of these compounds had low affinity (K-i > 1 mu M) for diazepam-sensitive and diazepam-insensitive receptors, and did not share discriminative stimulus effects with flumazenil or midazolam. Ro 19-0528 (7-chloro-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one), a structurally related compound with full agonist actions at diazepam-sensitive GABA(A) receptors, had high diazepam-insensitive receptor affinity (K-i = 96 nM) and partially substituted for the discriminative stimulus effects of flumazenil. These results are consistent with stereospecific mediation of the discriminative stimulus effects of flumazenil through high affinity binding to diazepam-insensitive receptors in pigeons.
C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892.
RP ACRI, JB (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA.
NR 39
TC 16
Z9 16
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 MAY 24
PY 1995
VL 278
IS 3
BP 213
EP 223
DI 10.1016/0014-2999(95)00128-8
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RC027
UT WOS:A1995RC02700004
PM 7589157
ER

PT J
AU BOWEN, WD
   BERTHA, CM
   VILNER, BJ
   RICE, KC
AF BOWEN, WD
   BERTHA, CM
   VILNER, BJ
   RICE, KC
TI CB-64D AND CB-184 - LIGANDS WITH HIGH SIGMA(2) RECEPTOR AFFINITY AND
   SUBTYPE SELECTIVITY
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Note
DE SIGMA RECEPTOR; (SUBTYPE SELECTIVITY); PHENYLMORPHAN; OPIOID
ID BINDING-SITES; CELLS
AB Four members of a novel class of sigma (a) ligands were investigated for a subtype selectivity. (-)-1S,5S- and (+)-1R,5R-(E)-8-Benzylidene-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-64L and CB-64D, respectively) exhibited sigma(1) K-i=10.5 nM and 3063 nM; sigma(2) K-i=154 nM and 16.5 nM, respectively. The corresponding 3,4-dichloro derivatives, (-)-1S,5S- and (+)-1R,5R-(E)-8-(3,4-dichiorobenzylidene)-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-182 and CB-184, respectively) were also examined. CB-182 ((-)-isomer) showed sigma(1) and sigma(2) K-i=27.3 nM and 35.5 nM, respectively, whereas CB-184 ((+)-isomer) exhibited sigma(1) and sigma(2) K-i=7436 nM and 13.4 nM, respectively. Thus, the two a subtypes showed opposite enantioselectivity for these compounds, with(-)>(+) at sigma(1) and(+)>(-) at sigma(2). Importantly, CB-64D and CB-184 showed high sigma(2) affinity and, respectively, 185-fold and 554-fold selectivity for sigma(2) receptors over sigma(1). While high sigma(2) selectivity relative to sigma(1) was achieved with these compounds, they both exhibited high affinity at mu (mu) opioid receptors (K-i=37.6 nM and 4.5 nM, respectively). Despite this, CB-64D and CB-184 will be useful tools for further characterization of sigma(2) receptors.
RP BOWEN, WD (reprint author), NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BLDG 8,RM B1-23,8 CTR DR MSC 0815,BETHESDA,MD 20892, USA.
NR 12
TC 43
Z9 46
U1 0
U2 3
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 MAY 24
PY 1995
VL 278
IS 3
BP 257
EP 260
DI 10.1016/0014-2999(95)00176-L
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RC027
UT WOS:A1995RC02700011
PM 7589164
ER

PT J
AU NEMUKHIN, AV
   TOPOL, IA
   WEINHOLD, F
AF NEMUKHIN, AV
   TOPOL, IA
   WEINHOLD, F
TI STRUCTURE OF MAGNESIUM CLUSTER GRIGNARD-REAGENTS
SO INORGANIC CHEMISTRY
LA English
DT Article
ID DENSITY-FUNCTIONAL METHOD; ABINITIO; ENERGY; ATOM; MOLECULES; BOND; MG-2
AB Structures of the magnesium Grignard complexes CH3MgF, CH3MgMgF, CH3MgF(Mg), and CH3MgF(Mg-2) have been studied by ab initio methods of quantum chemistry, including self-consistent-field, many-body perturbation theory, and density functional theory techniques, Electronic distributions have been analyzed by means of natural bond orbital analysis. It has been found that magnesium atoms can be attached to the Grignard reagent CH3MgF, leading to a dimagnesium complex CH3MgF(Mg) and the trimagnesium species CH3MgF(Mg-2). The energy of the CH3MgF(Mg) complex is found to be lower than that of the previously known CH3MgMgF compound.
C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702.
   UNIV WISCONSIN,DEPT CHEM,MADISON,WI 53706.
   MOSCOW MV LOMONOSOV STATE UNIV,DEPT CHEM,MOSCOW 119899,RUSSIA.
RI Nemukhin, Alexander/P-9662-2015; 
OI Weinhold, Frank/0000-0002-9580-054X
NR 26
TC 36
Z9 36
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA PO BOX 57136, WASHINGTON, DC 20037-0136
SN 0020-1669
J9 INORG CHEM
JI Inorg. Chem.
PD MAY 24
PY 1995
VL 34
IS 11
BP 2980
EP 2983
DI 10.1021/ic00115a027
PG 4
WC Chemistry, Inorganic & Nuclear
SC Chemistry
GA RA186
UT WOS:A1995RA18600027
ER

PT J
AU EVERHART, J
   WRIGHT, D
AF EVERHART, J
   WRIGHT, D
TI DIABETES-MELLITUS AS A RISK FACTOR FOR PANCREATIC-CANCER - A
   METAANALYSIS
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID IMPAIRED GLUCOSE-TOLERANCE; PAST MEDICAL HISTORY; BEVERAGE CONSUMPTION;
   PLASMA-GLUCOSE; MORTALITY; METABOLISM; CARCINOMA; ALCOHOL; INSULIN;
   COFFEE
AB Objective.-To evaluate diabetes mellitus as a risk factor for pancreatic cancer with the consideration that diabetes may also be a consequence of pancreatic cancer.
   Data Sources.-Pertinent studies of diabetes mellitus and pancreatic cancer published between 1975 and 1994 were identified from a MEDLINE search and from citations in articles and books.
   Study Selection.-Twenty of a total of 30 case-control and cohort studies met the two inclusion criteria: cases with a duration of diabetes of at feast 1 year prior to either pancreatic cancer diagnosis or death and the ability to calculate an appropriate relative risk (RR) estimate and variance.
   Data Extraction and Synthesis.-The pooled RR and 95% confidence interval (CI) of pancreatic cancer for diabetics relative to nondiabetics was 2.1 (1.6 to 2.8). There was a tendency for a higher RR for the nine cohort studies (RR, 2.6; 95% CI, 1.6 to 4.1) than for the II case-control studies (RR, 1.8; 95% CI, 1.1 to 2.7). Requiring diabetes duration of at least 5 years resulted in an RR of 2.0 (95% CI, 1.2 to 3.2).
   Conclusion.-Pancreatic cancer occurs with increased frequency among persons with long-standing diabetes.
C1 WESTAT CORP, ROCKVILLE, MD USA.
RP EVERHART, J (reprint author), NIDDKD, DIV DIGEST DIS & NUTR, NATCHER BLDG, ROOM 6AN-12J, 45 CTR DR MSC 6600, BETHESDA, MD 20892 USA.
NR 50
TC 422
Z9 439
U1 4
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 24
PY 1995
VL 273
IS 20
BP 1605
EP 1609
DI 10.1001/jama.273.20.1605
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA QY541
UT WOS:A1995QY54100028
PM 7745774
ER

PT J
AU COOPER, JR
AF COOPER, JR
TI INCLUDING NARCOTIC ADDICTION TREATMENT IN AN OFFICE-BASED PRACTICE
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID METHADONE-MAINTENANCE
RP COOPER, JR (reprint author), NIDA,DIV CLIN SERV & RES,5600 FISHERS LN,ROCKVILLE,MD 20857, USA.
NR 12
TC 25
Z9 26
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 MAY 24
PY 1995
VL 273
IS 20
BP 1619
EP 1620
DI 10.1001/jama.273.20.1619
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA QY541
UT WOS:A1995QY54100031
PM 7745777
ER

PT J
AU CHATFIELD, DC
   BROOKS, BR
AF CHATFIELD, DC
   BROOKS, BR
TI HIV-1 PROTEASE CLEAVAGE MECHANISM ELUCIDATED WITH MOLECULAR-DYNAMICS
   SIMULATION
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HUMAN IMMUNODEFICIENCY VIRUS-1; STATE-ANALOG INHIBITOR; ASPARTIC
   PROTEINASES; CHEMICAL MECHANISM; RHIZOPUS-CHINENSIS; 2.5-A RESOLUTION;
   TYPE-1 PROTEASE; BINDING; SITE; CHYMOTRYPSIN
AB The cleavage mechanism of HIV-1 protease is investigated with molecular dynamics simulation of substrate-, inhibitor-, and gem-diol intermediate-bound protease. Initial structures are based on X-ray crystallographic coordinates for the protease bound to the inhibitor JG-365.(1,2) The conformation space explored by atoms near the active site on the 100 ps time scale at 300 K is analyzed for structures likely to initiate reaction. Conformations suitable for reaction initiation are generated for both general acid-general base and direct nucleophilic attack mechanisms. The simulations suggest that (1) both types of mechanism are plausible; (2) the catalytic Asp of monomer B is protonated when reaction begins; (3) if the mechanism is general acid-general base, the catalytic Asp of monomer A is protonated when the second reaction step is initiated; (4) the carbonyl oxygen is more likely than the scissile nitrogen to be protonated in the early stages of reaction; (5) water 301(1) stabilizes productive conformations of reactants and intermediates, but it does not participate directly in reaction; and (6) a lytic water, if present, has very little mobility.
RP CHATFIELD, DC (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892, USA.
NR 59
TC 47
Z9 47
U1 0
U2 2
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 MAY 24
PY 1995
VL 117
IS 20
BP 5561
EP 5572
DI 10.1021/ja00125a018
PG 12
WC Chemistry, Multidisciplinary
SC Chemistry
GA QZ713
UT WOS:A1995QZ71300018
ER

PT J
AU KOWLESSUR, D
   YANG, XJ
   KAUFMAN, S
AF KOWLESSUR, D
   YANG, XJ
   KAUFMAN, S
TI FURTHER-STUDIES OF THE ROLE OF SER-16 IN THE REGULATION OF THE ACTIVITY
   OF PHENYLALANINE-HYDROXYLASE
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID RAT-LIVER; ACTIVATION; PHOSPHORYLATION; STIMULATION; PURIFICATION; SITE
AB It was previously proposed that the activation of rat liver phenylalanine hydroxylase (EC 1.14.16.1) by cAMP-dependent protein kinase-mediated phosphorylation of Ser-16 is due to the introduction of the negatively charged phosphate group, To explore the validity of this proposal, we have applied site-directed mutagenesis to specifically replace Ser-16 with negatively charged amino acids, glutamic and aspartic; with polar uncharged amino acids, asparagine and glutamine; with the positively charged amino acid lysine; and with the nonpolar hydrophobic amino acid alanine, The wild-type and mutant enzymes were purified to homogeneity, and the importance of Ser-16 in the activation of phenylalanine hydroxylase was examined by comparing the state of activation of the phosphorylated form of the wild-type hydroxylase with that of the mutants, The kinetic studies carried out on the wild-type phosphorylated hydroxylase showed that all the activation could be accounted for by an increase in V-max with no change in K-m for either phenylalanine or the pterin cofactor, Replacement of Ser-16 with a negatively charged residue, glutamate of aspartate, resulted in the activation of the hydroxylase by 2- to 4-fold, whereas replacement with glutamine, asparagine, lysine, or alanine resulted in a much more modest increase. Further, lysolecithin was found to stimulate the phosphorylated hydroxylase and the mutant enzymes S16E and S16D by a factor of 6-7, In contrast, the mutants S16Q, S16N, and S16A all showed the same magnitude of activation as the wild-type with lysolecithin, Therefore, this study demonstrates that activation of the enzyme by phosphorylation of Ser-16 by cAMP-dependent protein kinase is due to the introduction of negative charge(s) and strongly suggests the involvement of electrostatic interaction between the regulatory and catalytic domains of the hydroxylase.
RP KOWLESSUR, D (reprint author), NIMH,NEUROCHEM LAB,ROOM 3D30,BLDG 36,BETHESDA,MD 20892, USA.
NR 26
TC 25
Z9 25
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 23
PY 1995
VL 92
IS 11
BP 4743
EP 4747
DI 10.1073/pnas.92.11.4743
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RA150
UT WOS:A1995RA15000006
PM 7761394
ER

PT J
AU ALBINI, A
   BARILLARI, G
   BENELLI, R
   GALLO, RC
   ENSOLI, B
AF ALBINI, A
   BARILLARI, G
   BENELLI, R
   GALLO, RC
   ENSOLI, B
TI ANGIOGENIC PROPERTIES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE AIDS; KAPOSI SARCOMA; ANGIOGENESIS; VASCULAR CELL INVASION;
   MORPHOGENESIS
ID HUMAN-ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; CAPILLARY-LIKE
   STRUCTURES; FIBROBLAST GROWTH-FACTOR; KAPOSIS-SARCOMA-CELLS; LONG-TERM
   CULTURE; GENE-EXPRESSION; BASEMENT-MEMBRANE; TRANSGENIC MICE; IV
   COLLAGENASE
AB Extracellular human immunodeficiency virus type 1 (HIV-1) Tat protein promotes growth of spindle cells derived from AIDS-associated Kaposi sarcoma (AIDS-KS), an angioproliferative disease very frequent in HIV-1-infected individuals. Normal vascular cells, progenitors of AIDS-KS cells, proliferate in response to Tat after exposure to inflammatory cytokines, whose levels are augmented in HIV-l-infected individuals and in KS lesions. Here we show that Tat also promotes AIDS-KS and normal vascular cells to migrate and to degrade the basement membrane and stimulates endothelial cell morphogenesis on a matrix substrate. These effects are obtained at picomolar concentrations of exogenous Tat and are promoted by the treatment of the cells with the same inflammatory cytokines stimulating expression of the receptors for Tat, the integrins alpha(5) beta(1) and alpha(v) beta(3). Thus, under specific circumstances, Tat has angiogenic properties. As Tat and its receptors are present in AIDS-KS lesions, these data may explain some of the mechanisms by which Tat can induce angiogenesis and cooperate in the development of AIDS-KS.
C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892.
   IST NAZL RIC CANC,I-16132 GENOA,ITALY.
RI Ensoli, Barbara/J-9169-2016
OI Ensoli, Barbara/0000-0002-0545-8737
NR 45
TC 185
Z9 186
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 23
PY 1995
VL 92
IS 11
BP 4838
EP 4842
DI 10.1073/pnas.92.11.4838
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RA150
UT WOS:A1995RA15000025
PM 7539135
ER

PT J
AU HACKSTADT, T
   SCIDMORE, MA
   ROCKEY, DD
AF HACKSTADT, T
   SCIDMORE, MA
   ROCKEY, DD
TI LIPID-METABOLISM IN CHLAMYDIA TRACHOMATIS-INFECTED CELLS - DIRECTED
   TRAFFICKING OF GOLGI-DERIVED SPHINGOLIPIDS TO THE CHLAMYDIAL INCLUSION
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID COXIELLA-BURNETII; BREFELDIN-A; HOST-CELLS; APPARATUS; MEMBRANE;
   PSITTACI; SPHINGOMYELIN; PARASITISM; PROTEIN; FUSION
AB Chlamydia trachomatis undergoes its entire life cycle within an uncharacterized intracellular vesicle that does not fuse with lysosomes, We used a fluorescent Golgi-specific probe, {N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]}aminocaproylsphingosine (C-6-NBD-Cer), in conjunction with conventional fluorescence or confocal microscopy to identify interactions between the Golgi apparatus and the chlamydial inclusion, We observed not only a close physical association between the Golgi apparatus and the chlamydial inclusion but the eventual presence of a metabolite of this fluorescent probe associated with the chlamydiae themselves, Sphingomyelin, endogenously synthesized from C-6-NBD-Cer, was specifically transported to the inclusion and incorporated into the cell wall of the intracellular chlamydiae, Incorporation of the fluorescent sphingolipid by chlamydiae was inhibited by brefeldin A. Chlamydiae therefore occupy a vesicle distal to the Golgi apparatus that receives anterograde vesicular traffic from the Golgi normally bound for the plasma membrane, Collectively, the data suggest that the chlamydial inclusion may represent a unique compartment within the trans-Golgi network.
RP HACKSTADT, T (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HOST PARASITE INTERACT SECT,HAMILTON,MT 59840, USA.
NR 28
TC 238
Z9 240
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 23
PY 1995
VL 92
IS 11
BP 4877
EP 4881
DI 10.1073/pnas.92.11.4877
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RA150
UT WOS:A1995RA15000033
PM 7761416
ER

PT J
AU PINEAU, T
   FERNANDEZSALGUERO, P
   LEE, SST
   MCPHAIL, T
   WARD, JM
   GONZALEZ, FJ
AF PINEAU, T
   FERNANDEZSALGUERO, P
   LEE, SST
   MCPHAIL, T
   WARD, JM
   GONZALEZ, FJ
TI NEONATAL LETHALITY ASSOCIATED WITH RESPIRATORY-DISTRESS IN MICE LACKING
   CYTOCHROME-P450 1A2
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID STEM-CELLS; GENE; SUPERFAMILY; DISRUPTION; ACTIVATION; SEQUENCES;
   EVOLUTION; OXIDATION
AB Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals. This protein is primarily involved in oxidative metabolism of xenobiotics and is capable of metabolically activating numerous procarcinogens including aflatoxin B1, arylamines, heterocyclic amine food mutagens, and polycylic aromatic hydrocarbons. Expression of CYP1A2 is induced after exposure to certain aromatic hydrocarbons (i.e., 2,3,7,8-tetrachlorodibenzo-p-dioxin). Direct evidence for a role of CYP1A2 in any physiological or developmental pathway has not been documented. We now demonstrate that mice homozygous for a targeted mutation in the Cyp1a-2 gene are nonviable. Lethality occurs shortly after birth with symptoms of severe respiratory distress. Mutant neonates display impaired respiratory function associated with histological signs of lung immaturity, lack of air in alveoli at birth, and changes in expression of surfactant apoprotein in alveolar type II cells. The penetrance of the phenotype is not complete (19 mutants survived to adulthood out of 599 mice). Surviving animals, although lacking expression of CYP1A2, appear to be normal and are able to reproduce. These findings establish that CYP1A2 is critical for neonatal survival by influencing the physiology of respiration in neonates, thus offering etiological insights for neonatal respiratory distress syndrome.
C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892.
   NIMH,MOLEC GENET UNIT,BETHESDA,MD 20892.
   NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702.
OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027
NR 32
TC 79
Z9 80
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 23
PY 1995
VL 92
IS 11
BP 5134
EP 5138
DI 10.1073/pnas.92.11.5134
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RA150
UT WOS:A1995RA15000086
PM 7761462
ER

PT J
AU MOFENSON, LM
   RODRIGUEZ, EM
   HERSHOW, R
   FOX, HE
   LANDESMAN, S
   TUOMALA, R
   DIAZ, C
   DANIELS, E
   BRAMBILLA, D
AF MOFENSON, LM
   RODRIGUEZ, EM
   HERSHOW, R
   FOX, HE
   LANDESMAN, S
   TUOMALA, R
   DIAZ, C
   DANIELS, E
   BRAMBILLA, D
TI MYCOBACTERIUM-TUBERCULOSIS INFECTION IN PREGNANT AND NONPREGNANT WOMEN
   INFECTED WITH HIV IN THE WOMEN AND INFANTS TRANSMISSION STUDY
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTRAVENOUS-DRUG-USERS; SKIN-TEST; RISK;
   HEPATITIS; ANERGY; DEATHS
AB Background: Prevalence of Mycobacterium tuberculosis (TB) infection and anergy were evaluated in a cohort of pregnant and nonpregnant women infected with the human immunodeficiency virus who were enrolled in a prospective natural history study (the Women and Infants Transmission Study) conducted in New York, NY; Boston and Worcester, Mass; Chicago, ill, and San Juan, Puerto Rico.
   Methods: One hundred eighty-three women (65 pregnant, 118 nonpregnant) were evaluated for TB. The TB history and risk factors were assessed by interview and medical record review. Intradermal skin testing with tuberculin, mumps, and tetanus antigens and CD4(+) lymphocyte count were performed.
   Results: Overall prevalence of TB infection or disease by documented medical history and/or a tuberculin skin test induration of 5 mm or more was 14% (26 of 183). History of TB infection or disease was documented in 11% of the women who were interviewed. Tuberculin and anergy skin test results were evaluable for 124 women; 6% (seven of 124) had tuberculin skin test induration of 5 mm or more, including 11% (five of 46) of the pregnant women who were tested. Induration between 2 and 5 mm was observed in four more women, three of whom were pregnant. Anergy was observed in 42% (52 of 124); prevalence of anergy was higher in nonpregnant women (38 [49%] of 78) than in pregnant women (14 [30%] of 46). While anergy was more common in women with a CD4(+) cell count of 0.5 X 10(9)/L or less, 27% of those with a CD4(+) cell count of more than 0.5 X 10(9)/L were also anergic.
   Conclusion: These data support current Public Health Service recommendations for tuberculin skin testing in persons infected with the human immunodeficiency virus, and emphasize that evaluation should include pregnant as well as nonpregnant women. The prevalence of anergy does not appear increased in pregnancy in women infected with the human immunodeficiency virus. Health care providers should include tuberculin and anergy skin testing as part of the standard prenatal care for women infected with the human immunodeficiency virus.
C1 NIH,ROCKVILLE,MD.
   UNIV ILLINOIS,SCH PUBL HLTH,COLL MED,CHICAGO,IL.
   COLUMBIA UNIV,COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032.
   SUNY HLTH SCI CTR,BROOKLYN,NY 11203.
   BRIGHAM & WOMENS HOSP,BOSTON,MA 02115.
   UNIV PUERTO RICO,SAN JUAN,PR 00936.
   HLTH RESOURCES & SERV ADM,ROCKVILLE,MD.
   NEW ENGLAND RES INST,WATERTOWN,MA 02172.
OI Mofenson, Lynne/0000-0002-2818-9808
NR 31
TC 23
Z9 24
U1 0
U2 3
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 MAY 22
PY 1995
VL 155
IS 10
BP 1066
EP 1072
DI 10.1001/archinte.155.10.1066
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA QY911
UT WOS:A1995QY91100009
PM 7748050
ER

PT J
AU PEARCE, R
   GALDZICKI, Z
   RAPOPORT, SI
AF PEARCE, R
   GALDZICKI, Z
   RAPOPORT, SI
TI DECREASED SENSITIVITY TO NERVE GROWTH-FACTOR OF DORSAL-ROOT GANGLION
   NEURONS CULTURED FROM MOUSE TRISOMY-16, A MODEL OF DOWNS-SYNDROME
SO BRAIN RESEARCH
LA English
DT Article
DE NEURONAL ADHESION; DOWNS SYNDROME; DORSAL ROOT GANGLION; NERVE GROWTH
   FACTOR; MURINE TRISOMY 16
ID SENSORY NEURONS; NEUROTROPHIC FACTOR; NEURITE OUTGROWTH; EXPRESSION;
   RECEPTORS; ADHESION; FETUS; BRAIN; CELLS; NGF
AB The effect of NGF was studied on the adhesion of mouse dorsal root ganglion (DRG) neurons to a laminin-coated surface and on their subsequent survival in primary culture. DRG neurons were obtained both from normal diploid mice and trisomy 16 mice. The latter are considered a model of human trisomy 21, Down's syndrome. Whereas both diploid and trisomy DRG neurons depended on NGF for adhesion, the sensitivity of trisomy 16 neurons to NGF was significantly reduced (P < 0.05). This suggests that excess expression of genes on mouse chromosome 16 alters NGF-regulated adhesion to laminin. Survival of neurons that had attached to laminin in culture did not appear dependent on NGF for either diploid or trisomy 16 neurons.
RP PEARCE, R (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892, USA.
NR 40
TC 8
Z9 8
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 MAY 22
PY 1995
VL 680
IS 1-2
BP 108
EP 116
DI 10.1016/0006-8993(95)00251-K
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA RA270
UT WOS:A1995RA27000013
PM 7663966
ER

PT J
AU GU, ML
   RAPPAPORT, J
   LEPPLA, SH
AF GU, ML
   RAPPAPORT, J
   LEPPLA, SH
TI FURIN IS IMPORTANT BUT NOT ESSENTIAL FOR THE PROTEOLYTIC MATURATION OF
   GP160 OF HIV-1
SO FEBS LETTERS
LA English
DT Article
DE FURIN; HIV ENVELOPE; FURIN-DEFICIENT CHO
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PSEUDOMONAS EXOTOXIN-A; ENDOPROTEOLYTIC
   CLEAVAGE; ENVELOPE GLYCOPROTEIN; T4 MOLECULE; MOUSE FURIN; ACTIVATION;
   RETROVIRUS; INHIBITION; EXPRESSION
AB The envelope glycoproteins of HIV are required for viral infectivity. Proteolgsis of the Precursor envelope glycoprotein gp160 results in the formation of gp120 acid gp41. Cleavage occurs after the sequence Arg-Glu-Lys-Arg. This sequence is expected to be a substrate for the cellular protease furin. We examined whether furin is responsible for cleavage of gp160 by using a furin-deficient CHO cell line and the same cell line transfected with furin cDNA. Data obtained from viral transmission assays suggested that furin increased viral infectivity but was not essential for the maturation of gp160, implying that other proprotein processing enzymes also recognize this putative furin cleavage site.
C1 NATL INST HLTH,NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892.
   NATL INST HLTH,NIDR,ORAL MED LAB,BETHESDA,MD 20892.
NR 32
TC 30
Z9 30
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD MAY 22
PY 1995
VL 365
IS 1
BP 95
EP 97
DI 10.1016/0014-5793(95)00447-H
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA RA824
UT WOS:A1995RA82400022
PM 7774724
ER

PT J
AU SMOLEN, P
AF SMOLEN, P
TI A MODEL FOR GLYCOLYTIC OSCILLATIONS BASED ON SKELETAL-MUSCLE
   PHOSPHOFRUCTOKINASE KINETICS
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
ID PURINE NUCLEOTIDE CYCLE; FRUCTOSE 2,6-BISPHOSPHATE; CONTROL FEATURES;
   EXTRACTS; GLUCOSE; ISLETS; MODULATION; CITRATE; CA2+; ATP
AB Existing models for glycolytic oscillations are not based on detailed experimental kinetics of the glycolytic ,enzymes. Here; a model is constructed to fit the kinetics of skeletal muscle phosphofructokinase with respect to variations in AMP, ATP, fructose-6-P, and fructose 1,6-P-2 levels. A Monod-Wyman-Changeux model for a tetrameric enzyme is considered. However, it is found that the kinetic data fit considerably better with an assumption of identical, independent subunits. With parameters that fit these data and with a previous model for the rest of glycolysis, product activation of phosphofructokinase leads to oscillations of glycolytic intermediates and [ATP] resembling those observed experimentally in muscle extracts. The period is several minutes. The model can also produce oscillations at neutral pH and with [ATP] representative of an intact cell. Under both conditions the mean concentrations and oscillations vary with the rate of glucose phosphorylation in a plausible manner only if some amount of glucose-6-phosphatase or glucose-6-P dehydrogenase activity is assumed or if hexokinase is inhibited by glucose-6-P. Also, the model can be reduced to two variables for ease of analysis and the oscillation mechanism thereby illustrated.
C1 NIDDK,MATH RES BRANCH,BETHESDA,MD 20892.
NR 51
TC 43
Z9 44
U1 0
U2 2
PU ACADEMIC PRESS (LONDON) LTD
PI LONDON
PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX
SN 0022-5193
J9 J THEOR BIOL
JI J. Theor. Biol.
PD MAY 21
PY 1995
VL 174
IS 2
BP 137
EP 148
DI 10.1006/jtbi.1995.0087
PG 12
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology
GA RB674
UT WOS:A1995RB67400003
PM 7643610
ER

PT J
AU LEE, SP
   CENSULLO, ML
   KIM, HG
   KNUTSON, JR
   HAN, MK
AF LEE, SP
   CENSULLO, ML
   KIM, HG
   KNUTSON, JR
   HAN, MK
TI CHARACTERIZATION OF ENDONUCLEOLYTIC ACTIVITY OF HIV-1 INTEGRASE USING A
   FLUOROGENIC SUBSTRATE
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESONANCE ENERGY-TRANSFER; DNA
   INTEGRATION; VIRAL-DNA; RETROVIRUS INTEGRATION; ESCHERICHIA-COLI;
   PROTEIN INVITRO; NUCLEOTIDES; DISTANCES; CLEAVAGE
AB Retroviruses require viral DNA to be synthesized by reverse transcription in the cytoplasm followed by integration of the resulting viral DNA into the host chromosome in the nucleus, Reverse transcription and integration, essential steps in the Life cycle of retroviruses, are possible targets in the development of antiviral reagents. One attractive target is the integrase protein, a product of the retroviral pol gene which is solely responsible for the retroviral integration process through cutting and joining reactions. When screening for massive numbers of antiviral agents, a rapid and precise assay is ideal. We report the application of fluorescence resonance energy transfer (FRET) with fluorescein and eosin as the energy transfer pair to characterize HIV-IN-mediated DNA cleavage reactions. Past concerns with applications of FRET to DNA were due to interactions of the fluorophore with the DNA, resulting in quenched fluorescence. However, in this study these concerns have been resolved with the use of a nucleotide analog with a 12-carbon linker arm, 5-amino (12)-2'-deoxyuridine beta-cyanoethyl phosphoramidite, Steady-state fluorescence studies show that cleavage of the fluorogenic substrate by integrase results in enhancement of quenched donor fluorescence intensity, The fluorescence assay was confirmed by autoradiographic analysis of the cleavage reaction with radiolabeled fluorogenic substrate. This fluorescence assay will facilitate both detailed kinetic studies and the rapid screening of novel integrase inhibitors. (C) 1995 Academic Press, Inc.
C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007.
   NHLBI,BETHESDA,MD 20892.
NR 38
TC 25
Z9 25
U1 2
U2 6
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD MAY 20
PY 1995
VL 227
IS 2
BP 295
EP 301
DI 10.1006/abio.1995.1284
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA RC014
UT WOS:A1995RC01400006
PM 7573950
ER

PT J
AU POLYMEROPOULOS, MH
   POUSH, J
   RUBENSTEIN, JR
   FRANCOMANO, CA
AF POLYMEROPOULOS, MH
   POUSH, J
   RUBENSTEIN, JR
   FRANCOMANO, CA
TI LOCALIZATION OF THE GENE (SYM1) FOR PROXIMAL SYMPHALANGISM TO
   HUMAN-CHROMOSOME 17Q21-Q22
SO GENOMICS
LA English
DT Article
ID LINKAGE
AB Proximal symphalangism, or Cushing symphalangism (MIM: 185800), is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints. Conductive deafness and reduced flexibility of the ankles have also been observed in affected individuals. We have used polymorphic markers throughout the genome to perform genetic linkage analysis in subsequent generations of the family originally described by Harvey Cushing. We have established linkage for this disorder to markers on chromosome 17 (17q21-q22), with Z(max) = 6.98 at theta = 0.05 with marker D17S790. (C) 1995 Academic Press, Inc.
C1 JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21287 USA.
RP POLYMEROPOULOS, MH (reprint author), NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA.
NR 15
TC 30
Z9 33
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 20
PY 1995
VL 27
IS 2
BP 225
EP 229
DI 10.1006/geno.1995.1035
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700001
PM 7557985
ER

PT J
AU LAPPALAINEN, J
   ZHANG, L
   DEAN, M
   OZ, M
   OZAKI, N
   YU, DH
   VIRKKUNEN, M
   WEIGHT, F
   LINNOILA, M
   GOLDMAN, D
AF LAPPALAINEN, J
   ZHANG, L
   DEAN, M
   OZ, M
   OZAKI, N
   YU, DH
   VIRKKUNEN, M
   WEIGHT, F
   LINNOILA, M
   GOLDMAN, D
TI IDENTIFICATION, EXPRESSION, AND PHARMACOLOGY OF A CYS(23)-SER(23)
   SUBSTITUTION IN THE HUMAN 5-HT2C RECEPTOR GENE (HTR2C)
SO GENOMICS
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; CEREBROSPINAL-FLUID;
   META-CHLOROPHENYLPIPERAZINE; SEROTONIN FUNCTION; POINT MUTATIONS; PANIC
   DISORDER; MOUSE 5-HT1C; PERSONALITY; SUICIDE; SUBTYPE
AB The function of brain serotonin-2C (5-HT2C) receptors, including behavioral and neurochemical responses to 5-HT2C agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, we identified a Cys(23)-Ser(23) substitution (designated 5-HT2Ccys and 5-HT2Cser) in the first hydrophobic region of the human 5-HT2C receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respect to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT2C receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT2Ccys and 5-HT2Cser receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT2Ccys and 5-HT2Cser receptor proteins may not differ in their responses to serotonin under baseline physiological conditions. (C) 1995 Academic Press, Inc.
C1 NIAAA,DICBR,CLIN STUDIES LAB,ROCKVILLE,MD 20852.
   NIAAA,DICBR,MOLEC & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852.
   NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD.
   HELSINKI UNIV,DEPT PSYCHIAT,HELSINKI,FINLAND.
RP LAPPALAINEN, J (reprint author), NIAAA,DICBR,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA.
RI Oz, Murat/E-2148-2012; 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 43
TC 178
Z9 181
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 20
PY 1995
VL 27
IS 2
BP 274
EP 279
DI 10.1006/geno.1995.1042
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700008
PM 7557992
ER

PT J
AU ADOLPH, KW
   LONG, GL
   WINFIELD, S
   GINNS, EI
   BORNSTEIN, P
AF ADOLPH, KW
   LONG, GL
   WINFIELD, S
   GINNS, EI
   BORNSTEIN, P
TI STRUCTURE AND ORGANIZATION OF THE HUMAN THROMBOSPONDIN-3 GENE (THBS3)
SO GENOMICS
LA English
DT Article
ID MOUSE; EXPRESSION; MEMBER; FAMILY; 2ND; TRANSCRIPTS; PROMOTER; SEQUENCE;
   PROTEINS; INTRON
AB The promoter/5' flank sequence, cDNA sequence, and exon/intron structures of the human thrombospondin 3 (THBS3) gene have been determined. THBS3 cDNA clones were obtained by PCR amplification of human fetal lung cDNA using THBS3-specific primers. Analysis of cDNA and genomic sequences showed the THBS3 gene to be composed of 23 exons, 1 more than the number of exons in the previously characterized mouse TSP3 gene. The additional exon results from the division of mouse exon F into exons F1 and F2. The cDNA encodes a polypeptide of 956 amino acids that is highly acidic, with a clustering of acidic side chains in the third quarter of the polypeptide. This region corresponds to seven type III (Ca2+-binding) repeats, a feature shared with other thrombospondins. In addition to these type III repeats, four type II (EGF-like) repeats and NH2- and COOH-terminal domains are present in thrombospondin 3. The THBS3 and mouse TSP3 genes differ in intron sizes, but exon sequences and sizes and positions of insertion of introns are conserved to a high degree. The structural organization of the THBS3 gene is of interest because of its close proximity to that of metaxin, with which it shares a common promoter sequence, and to the gene encoding glucocerebrosidase, a deficiency in which causes Gaucher disease. (C) 1995 Academic Press, Inc.
C1 UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA 98195.
   NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892.
FU NIDCR NIH HHS [DE-08229]
NR 33
TC 21
Z9 22
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 MAY 20
PY 1995
VL 27
IS 2
BP 329
EP 336
DI 10.1006/geno.1995.1050
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700016
PM 7558000
ER

PT J
AU SHASTRY, BS
   HEJTMANCIK, JF
   PLAGER, DA
   HARTZER, MK
   TRESE, MT
AF SHASTRY, BS
   HEJTMANCIK, JF
   PLAGER, DA
   HARTZER, MK
   TRESE, MT
TI LINKAGE AND CANDIDATE GENE ANALYSIS OF X-LINKED FAMILIAL EXUDATIVE
   VITREORETINOPATHY
SO GENOMICS
LA English
DT Note
ID NORRIE DISEASE; MUTATIONS; IDENTIFICATION; POLYMORPHISMS; DISORDERS;
   REGION
AB Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Z(max) = 2.1, theta(max) = 0) and DXS228 (Z(max) = 0.5, theta(max) = 0.11), and this was further confirmed by multipoint analysis with these same markers (Z(max) = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient. (C) 1995 Academic Press, Inc.
C1 INDIANA UNIV,DEPT OPHTHALMOL,INDIANAPOLIS,IN 46202.
   NEI,BETHESDA,MD 20892.
   WILLIAM BEAUMONT HOSP,DEPT OPHTHALMOL,ROYAL OAK,MI 48073.
RP SHASTRY, BS (reprint author), OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48309, USA.
FU NEI NIH HHS [EY 05230]
NR 21
TC 39
Z9 41
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 20
PY 1995
VL 27
IS 2
BP 341
EP 344
DI 10.1006/geno.1995.1052
PG 4
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700018
PM 7558002
ER

PT J
AU MOCK, BA
   CONNELLY, MA
   MCBRIDE, OW
   KOZAK, CA
   MARCU, KB
AF MOCK, BA
   CONNELLY, MA
   MCBRIDE, OW
   KOZAK, CA
   MARCU, KB
TI CHUK, A CONSERVED HELIX-LOOP-HELIX UBIQUITOUS KINASE, MAPS TO
   HUMAN-CHROMOSOME-10 AND MOUSE CHROMOSOME-19
SO GENOMICS
LA English
DT Note
ID GENE; COMMITTEE; NEOPLASIA; P450IIE1
AB Helix-loop-helix proteins contain stretches of DNA that encode two amphipathic alpha-helices joined by a loop structure and are involved in protein dimerization and transcriptional regulation essential to a variety of cellular processes. CHUK, a newly described conserved helix-loop-helix ubiquitous kinase, was mapped by somatic cell hybrid analyses to human Chr 10q24-q25. Chuk and a related sequence, Chuk-rs1, were mapped to mouse chromosomes 19 and 16, respectively, by a combination of somatic cell hybrid, recombinant inbred, and backcross analyses. (C) 1995 Academic Press, Inc.
C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892.
   SUNY STONY BROOK,DEPT PATHOL,STONY BROOK,NY 11794.
   SUNY STONY BROOK,DEPT BIOCHEM & CELL BIOL,STONY BROOK,NY 11794.
RP MOCK, BA (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA.
FU NCI NIH HHS [N01-CB-21075, CA 36246]
NR 17
TC 19
Z9 21
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 20
PY 1995
VL 27
IS 2
BP 348
EP 351
DI 10.1006/geno.1995.1054
PG 4
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700020
PM 7558004
ER

PT J
AU SANGO, K
   JOHNSON, ON
   KOZAK, CA
   PROIA, RL
AF SANGO, K
   JOHNSON, ON
   KOZAK, CA
   PROIA, RL
TI BETA-1,4-N-ACETYLGALACTOSAMINYLTRANSFERASE INVOLVED IN GANGLIOSIDE
   SYNTHESIS - CDNA SEQUENCE, EXPRESSION, AND CHROMOSOME MAPPING OF THE
   MOUSE GENE
SO GENOMICS
LA English
DT Note
ID CLONING; GM2
AB beta-1,4-N-Acetylgalactosaminyltransferase (EC 2.4.1.92; GalNAc-T) is a glycosyltransferase involved in the synthesis of gangliosides G(M2) and G(D2) as well as glycolipid G(A2). We have isolated and sequenced the mouse GalNAc-T cDNA, studied GalNAc-T mRNA expression in adult tissues and in embryos, and determined the chromosomal location of the GalNAc-T gene, Ggm2. In comparison with the human cDNA, the mouse sequence was 83 and 87% identical at the nucleic acid and amino acid levels, respectively. The GalNAc-T transcript was most abundantly expressed in brain, liver, lung, spleen, and testis among the eight adult tissues examined. Relatively high levels of expression were seen early in mouse development (7-day embryos) compared to later times (11, 15, and 17 days). The Ggm2 gene was mapped to a distal position on mouse chromosome 10 that is homologous to a portion of human chromosome 12. (C) 1995 Academic Press, Inc.
C1 NIDDKD,GENET & BIOCHEM BRANCH,BIOCHEM GENET SECT,BETHESDA,MD 20892.
   NIAID,BETHESDA,MD 20892.
RI Proia, Richard/A-7908-2012
NR 13
TC 16
Z9 17
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 MAY 20
PY 1995
VL 27
IS 2
BP 362
EP 365
DI 10.1006/geno.1995.1058
PG 4
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA RD687
UT WOS:A1995RD68700024
PM 7558008
ER

PT J
AU BENBARUCH, A
   MICHIEL, DF
   OPPENHEIM, JJ
AF BENBARUCH, A
   MICHIEL, DF
   OPPENHEIM, JJ
TI SIGNALS AND RECEPTORS INVOLVED IN RECRUITMENT OF INFLAMMATORY CELLS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID TUMOR-NECROSIS-FACTOR; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; NEUTROPHIL
   CHEMOTACTIC FACTOR; HOST DEFENSE CYTOKINES; NF-KAPPA-B; INTERLEUKIN-8
   GENE; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL-4-PHOSPHATE KINASE; TYROSINE
   PHOSPHORYLATION; COOPERATIVE INTERACTION
C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702.
RP BENBARUCH, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA.
NR 77
TC 336
Z9 338
U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 19
PY 1995
VL 270
IS 20
BP 11703
EP 11706
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600001
PM 7744810
ER

PT J
AU KANNO, T
   BROWN, K
   SIEBENLIST, U
AF KANNO, T
   BROWN, K
   SIEBENLIST, U
TI EVIDENCE IN SUPPORT OF A ROLE FOR HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX
   IN ACTIVATING NF-KAPPA-B VIA STIMULATION OF SIGNALING PATHWAYS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Note
ID HTLV-I; P50
AB The human T-cell leukemia virus type I Tax protein activates NF-kappa B transcription factors from preformed cytoplasmic pools, including those pools that are retained by the I kappa B-alpha inhibitory protein. Degradation of I kappa B-alpha is enhanced by Tax, resulting in the liberation of some NF-kappa B, which then translocates into the nucleus. Here we have investigated the mechanism by which Tax causes degradation of I kappa B-alpha. Two I kappa B-alpha mutants defective in extracellular signal induced degradation of I kappa B-alpha also blocked Tax-mediated kappa B-dependent transactivation when cotransfected into Jurkat T cells. Cotransfected wild-type I kappa B-alpha or an irrelevant mutant did not significantly effect transactivation induced by Tax. The signal-defective I kappa B-alpha proteins are mutated at either of two closely spaced serines in the N terminus of the protein (Ser(32) and Ser(36)). In wild-type I kappa B-alpha one or both of these serines are inducibly phosphorylated with extracellular stimuli, and such phosphorylation appears necessary for subsequent degradation and thus activation of NF-kappa B. These results suggest that Tax triggers I kappa B-alpha degradation and thus NF-kappa B activation by a mechanism that converges with that induced by extracellular stimulation such as phorbol 12-myristate 13-acetate/ionomycin or tumor necrosis factor alpha. A role for Tax in activating signal transduction pathways upstream of I kappa B-alpha is implied.
C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892.
NR 15
TC 49
Z9 49
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 MAY 19
PY 1995
VL 270
IS 20
BP 11745
EP 11748
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600012
PM 7744820
ER

PT J
AU AMIN, N
   PETERKOFSKY, A
AF AMIN, N
   PETERKOFSKY, A
TI A DUAL MECHANISM FOR REGULATING CAMP LEVELS IN ESCHERICHIA-COLI
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SENSITIVE ADENYLATE CYCLASE; PHOSPHODIESTERASE; PHOSPHATE
AB In Escherichia coli, inorganic orthophosphate regulates cAMP levels by acting at two separate loci. First, adenylyl cyclase activity measured in permeabilized cells of E. coli is substantially stimulated by physiological concentrations of inorganic phosphate. This stimulation does not require the presence of cAMP phosphodiesterase activity. Second, measurements of cAMP phosphodiesterase activity in permeabilized cells show a dose dependent inhibition of that activity by inorganic orthophosphate. A model is proposed in which inorganic orthophosphate serves as a multifaceted regulator of cAMP levels by both stimulating synthesis and inhibiting degradation of the nucleotide.
C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892.
NR 15
TC 16
Z9 17
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 MAY 19
PY 1995
VL 270
IS 20
BP 11803
EP 11805
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600023
PM 7744829
ER

PT J
AU LEI, KJ
   PAN, CJ
   LIU, JL
   SHELLY, LL
   CHOU, JY
AF LEI, KJ
   PAN, CJ
   LIU, JL
   SHELLY, LL
   CHOU, JY
TI STRUCTURE-FUNCTION ANALYSIS OF HUMAN GLUCOSE-6-PHOSPHATASE, THE
   ENZYME-DEFICIENT IN GLYCOGEN-STORAGE-DISEASE TYPE 1A
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MICROSOMAL GLUCOSE-6-PHOSPHATASE; 6-PHOSPHOFRUCTO-2-KINASE
   FRUCTOSE-2,6-BISPHOSPHATASE; ALKALINE-PHOSPHATASE; PROTEINS; SYSTEM;
   MUTAGENESIS; MUTATIONS; MECHANISM; CATALYSIS; GENE
AB Glucose-6-phosphatase (G6Pase) is the enzyme deficient in glycogen storage disease type 1a, an autosomal recessive disorder. We have previously identified six mutations in the G6Pase gene of glycogen storage disease type 1a patients and demonstrated that these mutations abolished or greatly reduced enzymatic activity of G6Pase, a hydrophobic protein of 357 amino acids. Of these, four mutations (R83C, R295C, G222R, and Q347X) are missense and one (Q347X) generates a truncated G6Pase of 346 residues. To further understand the roles and structural requirements of amino acids 83, 222, 295, and those at the carboxyl terminus in G6Pase catalysis, we characterized mutant G6Pases generated by near-saturation mutagenesis of the aforementioned amino acids. Substitution of Arg-83 with amino acids of diverse structures including Lys, a conservative change, yielded mutant G6Pase with no enzymatic activity. On the other hand, substitution of Arg-295 with Lys (R295K) retained high activity, and R295N, R295S, and R295Q exhibited moderate activity. All other substitutions of Arg-295 had no G6Pase activity, suggesting that the role of Arg-295 is to stabilize the protein either by salt bridge or hydrogen-bond formation. Substitution of Gly-222, however, remained functional unless a basic (Arg or Lys), acidic (Asp), or large polar (Gin) residue was introduced, consistent with the hydrophobic requirement of codon 222, which is predicted to be in the fourth membrane-spanning domain. It is possible that Arg-83 is involved in stabilizing the enzyme (His)-phosphate intermediate formed during G6Pase catalysis. There exist 9 conserved His residues in human G6Pase. His-9, His-119, His-252, and His-353 reside on the same side of the endoplasmic reticulum membrane as Arg-83. Whereas H119A mutant G6Pase had no enzymatic activity, H9A, H252A, and H353A mutant G6Pases retained significant activity. Substitution of His-119 with amino acids of diverse structures also yielded mutant G6Pase with no activity, suggesting that His-119 is the phosphate acceptor in G6Pase catalysis. We also present data demonstrating that the carboxyl-terminal 8 residues in human G6Pase are not essential for G6Pase catalysis.
C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892.
NR 25
TC 60
Z9 62
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 MAY 19
PY 1995
VL 270
IS 20
BP 11882
EP 11886
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600034
PM 7744838
ER

PT J
AU DONKERSLOOT, JA
   THOMPSON, J
AF DONKERSLOOT, JA
   THOMPSON, J
TI CLONING, EXPRESSION, SEQUENCE-ANALYSIS, AND SITE-DIRECTED MUTAGENESIS OF
   THE TN5306-ENCODED N-5-(CARBOXYETHYL)ORNITHINE SYNTHASE FROM
   LACTOCOCCUS-LACTIS K1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COMPLETE NUCLEOTIDE-SEQUENCE; BACTERIOPHAGE-T7 DNA-POLYMERASE;
   GLUTAMATE-DEHYDROGENASE GENE; LACTATE-DEHYDROGENASE; ESCHERICHIA-COLI;
   PLASMID DNA; STREPTOCOCCUS-LACTIS; CONJUGATIVE TRANSPOSON;
   BACILLUS-SUBTILIS; BINDING SITES
AB The gene (ceo) encoding N-5-(carboxyethyl) ornithine synthase (EC 1.5.1.24) has been isolated from the sucrose-nisin transposon Tn5306 of Lactococcus lactis K1, sequenced, and expressed at high level in Escherichia coli. The cloned enzyme has allowed the synthesis of the novel N-omega-carboxypropyl amino acids N-5-(1-carboxypropyl)-L-ornithine and N-6-(1-carboxypropyl)-L-lysine. Comparison of the deduced amino acid sequence of N-5-(1-carboxyethyl)-L-ornithine synthase (M(r) = 35,323) to the functionally analogous octopine and nopaline synthases from crown gall tumors showed surprisingly little similarity. However, N-5-(1-carboxyethyl)-L-ornithine synthase and yeast saccharopine dehydrogenase exhibit homology at their N and C termini, which suggests that these two proteins constitute a distinct branch of the amino acid dehydrogenase superfamily. A centrally located 9-amino acid segment (GSGNVAQGA) in N-5-(1-carboxyethyl)-L-ornithine synthase is virtually identical with a sequence present in the beta alpha beta-fold of the nucleotide binding domain of several microbial NADPH-dependent glutamate dehydrogenases. A much longer sequence of similar to 80 residues has significant similarity to alanine dehydrogenase. Substitution of arginine 15 of N-5-(1-carboxyethyl)-L-ornithine synthase by lysine resulted in loss of enzyme activity.
RP NIDR, MICROBIAL ECOL LAB, BLDG 30, RM 316, 30 CONVENT DR MSC 4350, BETHESDA, MD 20892 USA.
NR 74
TC 14
Z9 15
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 MAY 19
PY 1995
VL 270
IS 20
BP 12226
EP 12234
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600078
PM 7744873
ER

PT J
AU VAISMAN, BL
   KLEIN, HG
   ROUIS, M
   BERARD, AM
   KINDT, MR
   TALLEY, GD
   MEYN, SM
   HOYT, RF
   MARCOVINA, SM
   ALBERS, JJ
   HOEG, JM
   BREWER, HB
   SANTAMARINAFOJO, S
AF VAISMAN, BL
   KLEIN, HG
   ROUIS, M
   BERARD, AM
   KINDT, MR
   TALLEY, GD
   MEYN, SM
   HOYT, RF
   MARCOVINA, SM
   ALBERS, JJ
   HOEG, JM
   BREWER, HB
   SANTAMARINAFOJO, S
TI OVEREXPRESSION OF HUMAN LECITHIN-CHOLESTEROL ACYLTRANSFERASE LEADS TO
   HYPERALPHALIPOPROTEINEMIA IN TRANSGENIC MICE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEINS; APOLIPOPROTEIN-A-I; HEPATIC LIPASE
   DEFICIENCY; ESTER TRANSFER PROTEIN; GENE; PLASMA; RECEPTOR; SEQUENCE;
   LIVER; ATHEROGENESIS
AB Lecithin cholesterol acyltransferase (LCAT) is a key enzyme which catalyzes the esterification of free cholesterol present in plasma lipoproteins. In order to evaluate the role of LCAT in HDL metabolism, a 6.2-kilobase (kb) fragment consisting of 0.851 and 1.134 kb of the 5'- and 3'-flanking regions, as well as the entire human LCAT gene, was utilized to develop transgenic mice. Three different transgenic mouse lines overexpressing human LCAT at plasma levels 11-, 14-, and 109-fold higher than non-transgenic mice were established, Northern blot hybridization analysis demonstrated that the injected 6.2-kb fragment contained the necessary DNA sequences to direct tissue specific expression of the human LCAT gene in mouse liver. Compared to age- and sex-matched controls, total cholesterol and HDL cholesterol levels were increased in all 3 transgenic mice lines by 124-218 and 123-194%, respectively, while plasma triglyceride concentrations remained similar to that of control animals. Fast protein liquid chromatography analysis of transgenic mouse plasma revealed marked increases in high density lipo-sportin (HDL)-cholesteryl ester and phospholipid as well as the formation of larger size HDL. Thus, the majority of the increase in transgenic plasma cholesterol concentrations was due to accumulation of cholesteryl ester in HDL consistent with enhanced esterification of free cholesterol in mouse HDL by human LCAT. Plasma concentrations of apoA-I, apoA-II, and apoE were increased in high expressor homozygote mice who also demonstrated an accumulation of an apoE-rich HDL(1). Like the mouse enzyme, human LCAT was found to be primarily associated with mouse HDL. Our studies demonstrate a high correlation between plasma LCAT activity and total as well as HDL cholesterol levels establishing that in mice LCAT modulates plasma HDL concentrations. Overexpression of LCAT in mice leads to HDL elevation as well as increased heterogeneity of the HDL lipoprotein particles, indicating that high levels of plasma LCAT activity may be associated with hyperalphalipoproteinemia and enhanced reverse cholesterol transport.
C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892.
   NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892.
   UNIV WASHINGTON,SCH MED,DEPT MED,NW LIPID RES CTR,SEATTLE,WA 98103.
RI Rouis, Mustapha/E-4993-2016
FU NHLBI NIH HHS [HL30086]
NR 47
TC 97
Z9 97
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 MAY 19
PY 1995
VL 270
IS 20
BP 12269
EP 12275
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600084
PM 7744879
ER

PT J
AU HAMAWY, MM
   MINOGUCHI, K
   SWAIM, WD
   MERGENHAGEN, SE
   SIRAGANIAN, RP
AF HAMAWY, MM
   MINOGUCHI, K
   SWAIM, WD
   MERGENHAGEN, SE
   SIRAGANIAN, RP
TI A 77-KDA PROTEIN ASSOCIATES WITH PP125(FAK) IN MAST-CELLS AND BECOMES
   TYROSINE-PHOSPHORYLATED BY HIGH-AFFINITY IGE RECEPTOR AGGREGATION
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LEUKEMIA RBL-2H3 CELLS; FOCAL ADHESION KINASE; IMMUNOGLOBULIN-E;
   HISTAMINE-RELEASE; FIBRONECTIN; ADHERENCE; PP125FAK; IDENTIFICATION;
   STIMULATION; ACTIVATION
AB The focal adhesion kinase, pp125(FAK), is a novel nonreceptor protein tyrosine kinase expressed in different cells including mast cells. Here we report that a 77-kDa protein associates with pp125(FAK) in the mast cell analog, rat basophilic leukemia (RBL-2H3) cells. When pp125(FAK) immunoprecipitates were subjected to an in vitro kinase assay, there was prominent phosphorylation on tyrosine of pp125(FAK) and of a 77-kDa protein. By V8 protease digestion mapping and by immunoblotting with two different anti-pp125(FAK) antibodies, the 77-kDa protein was distinct from pp125(FAK). This Fak Associated Protein or FAP was detected in RBL-2H3 cells but not in fibroblasts. The aggregation of the high affinity IgE receptor, Fc epsilon RI, induced the in vivo tyrosine phosphorylation of FAP. However, there was a marked decrease in the in vitro phosphorylation of FAP in the immunoprecipitates from Fc epsilon RI aggregated cells. Both of these Fc epsilon RI-mediated effects were enhanced by cell adhesion. There was strong association of FAP with non-tyrosine-phosphorylated pp125(FAK). Thus this interaction does not appear to be mediated by the Src homology 2 domain. Together the data indicate that FAP associates with pp125(FAK) and suggest that FAP may play a role in Fc epsilon RI signaling.
RP HAMAWY, MM (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA.
NR 47
TC 19
Z9 19
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 MAY 19
PY 1995
VL 270
IS 20
BP 12305
EP 12309
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QY736
UT WOS:A1995QY73600088
PM 7744883
ER

PT J
AU MA, Y
   ITO, Y
AF MA, Y
   ITO, Y
TI SEPARATION OF PEPTIDE DERIVATIVES BY PH-ZONE-REFINING COUNTERCURRENT
   CHROMATOGRAPHY
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article; Proceedings Paper
CT 1994 International Symposium on Preparative Chromatography
CY JUN 01-05, 1994
CL WASHINGTON, DC
SP WASHINGTON CHROMATOG DISCUSS GRP
AB pH-Zone-refining counter-current chromatography was applied to the preparative separation of oligopeptide derivatives containing up to three amino acids. Both acidic benzyloxycarbonyl peptides and basic peptides-beta-naphthylamide were successfully separated with two-phase solvent systems composed of methyl tert.-butyl ether, l-butanol, acetonitrile and water using a set of suitable retainer and eluent reagents for each group. The preparative ability of the method was demonstrated in the separation of multigram quantities of analyte with a standard separation column with a total capacity of 325 mi. The effects of important factors such as polarity of the two-phase solvent system, concentrations of the eluent base and the retainer acid were discussed.
C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892.
NR 19
TC 32
Z9 32
U1 0
U2 9
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 MAY 19
PY 1995
VL 702
IS 1-2
BP 197
EP 206
DI 10.1016/0021-9673(94)00852-Z
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA RA849
UT WOS:A1995RA84900017
PM 7599739
ER

PT J
AU KNIGHT, M
   FAGARASAN, MO
   TAKAHASHI, K
   GEBLAOUI, AZ
   MA, Y
   ITO, Y
AF KNIGHT, M
   FAGARASAN, MO
   TAKAHASHI, K
   GEBLAOUI, AZ
   MA, Y
   ITO, Y
TI SEPARATION AND PURIFICATION OF PEPTIDES BY HIGH-SPEED COUNTERCURRENT
   CHROMATOGRAPHY
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article; Proceedings Paper
CT 1994 International Symposium on Preparative Chromatography
CY JUN 01-05, 1994
CL WASHINGTON, DC
SP WASHINGTON CHROMATOG DISCUSS GRP
ID PHASE
AB Preparative separations of peptides have been accomplished using high-speed counter-current chromatography. This has been made possible by the use of a particular solvent system that does not exhibit solvent carryover at high speed flow and centrifugation conditions. The solvent system composed of tert.-butyl methyl ether, rt-butanol, acetonitrile and aqueous trifluoroacetic acid which can be adjusted in volume ratios and percent acid is employed in two instruments for counter-current chromatography. The cross-axis coil planet centrifuge was used for separation of various dipeptides. Superior resolution was obtained with the multi-layer coil planet centrifuge in the separation of six dipeptides and in the preparative purification of two synthetic peptides.
C1 PEPTIDE TECHNOL CORP,GAITHERSBURG,MD 20877.
   NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892.
OI Knight, Martha/0000-0003-4863-8858
NR 6
TC 13
Z9 14
U1 0
U2 8
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 MAY 19
PY 1995
VL 702
IS 1-2
BP 207
EP 214
DI 10.1016/0021-9673(94)01158-B
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA RA849
UT WOS:A1995RA84900018
PM 7599740
ER

PT J
AU JOHN, CS
   BOWEN, WD
   VARMA, VM
   MCAFEE, JG
   MOODY, TW
AF JOHN, CS
   BOWEN, WD
   VARMA, VM
   MCAFEE, JG
   MOODY, TW
TI SIGMA-RECEPTORS ARE EXPRESSED IN HUMAN NONSMALL CELL LUNG-CARCINOMA
SO LIFE SCIENCES
LA English
DT Article
DE SIGMA RECEPTORS; RADIOIODINATED BENZAMIDE; NONSMALL CELL LUNG CANCER
ID MALIGNANT-MELANOMA; BINDING; LIGAND; GROWTH; CANCER
AB N-(2-piperidinoethyl)4-iodobenzamide), IPAB, was used to characterize sigma receptors in non-small cell lung cancer (NSCLC) cell lines. (125)IPAB bound with high affinity to large cell carcinoma (NCI-H1299), adenocarcinoma (NCI-H838), and lung carcinoid (NCI-H727) cell lines. Specific IPAB binding was inhibited with high affinity by haloperidol (Ki 0.6 nM), IPAB (Ki = 14 nM) and 1,3-ditolyl guanidine (DTG) (Ki = 40 nM). Relative to other receptor ligands, IPAB was not readily internalized at 37 degrees C. IPAB had little effect on the growth of NSCLC cells. Scintigraphic imaging studies using (131)IPAB in nude mice bearing NCI-H838 xenografts visualized the tumor at 24 or 30 hours after injection. These results suggest that sigma receptors which are present on NSCLC cells may be used as external markers for imaging tumors in vivo.
C1 NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892.
   NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850.
RP JOHN, CS (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,661 ROSS HALL,2300 1 ST NW,WASHINGTON,DC 20037, USA.
FU NCI NIH HHS [CA58496]
NR 18
TC 42
Z9 44
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD MAY 19
PY 1995
VL 56
IS 26
BP 2385
EP 2392
DI 10.1016/0024-3205(95)00232-U
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA QZ865
UT WOS:A1995QZ86500010
PM 7791525
ER

PT J
AU DIMITROV, DS
   MARTIN, MA
AF DIMITROV, DS
   MARTIN, MA
TI HIV RESULTS IN THE FRAME
SO NATURE
LA English
DT Letter
ID VIRUS TYPE-1 INFECTION; KINETICS; PLASMA
C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892.
RP DIMITROV, DS (reprint author), NCI,MATH BIOL LAB,BLDG 10,BETHESDA,MD 20892, USA.
NR 9
TC 43
Z9 43
U1 0
U2 0
PU MACMILLAN MAGAZINES LTD
PI LONDON
PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF
SN 0028-0836
J9 NATURE
JI Nature
PD MAY 18
PY 1995
VL 375
IS 6528
BP 194
EP 195
DI 10.1038/375194b0
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QY881
UT WOS:A1995QY88100038
PM 7746314
ER

PT J
AU CHARACHE, S
   TERRIN, ML
   MOORE, RD
   DOVER, GJ
   BARTON, FB
   ECKERT, SV
   MCMAHON, RP
   BONDS, DR
   ORRINGER, E
   JONES, S
   STRAYHORN, D
   ROSSE, W
   PHILLIPS, G
   PEACE, D
   JOHNSONTELFAIR, A
   MILNER, P
   KUTLAR, A
   TRACY, A
   BALLAS, SK
   ALLEN, GE
   MOSHANG, J
   SCOTT, B
   STEINBERG, M
   ANDERSON, A
   SABAHI, V
   PEGELOW, C
   TEMPLE, D
   CASE, E
   HARRELL, R
   CHILDERIE, S
   EMBURY, S
   SCHMIDT, B
   DAVIES, D
   KOSHY, M
   TALISCHYZAHED, N
   DORN, L
   PENDARVIS, G
   MCGEE, M
   TELFER, M
   DAVIS, A
   CASTRO, O
   FINKE, H
   PERLIN, E
   SITEMAN, J
   GASCON, P
   DIPAOLO, P
   GARGIULO, S
   ECKMAN, J
   BAILEY, JH
   PLATT, A
   WALLER, L
   RAMIREZ, G
   KNORS, V
   HERNANDEZ, S
   RODRIGUEZ, EM
   WILKES, E
   VICHINSKY, E
   CLASTER, S
   EARLES, A
   KLEMAN, K
   MCLAUGHLIN, K
   SWERDLOW, P
   SMITH, W
   MADDOX, B
   USRY, L
   BRENNER, A
   WILLIAMS, K
   OBRIEN, R
   GENTHER, K
   SHURIN, S
   BERMAN, B
   CHIARUCCI, K
   KEVERLINE, L
   OLIVIERI, N
   SHAW, D
   LEWIS, N
   BRIDGES, K
   TYNAN, B
   WINOGRAD, C
   BELLEVUE, R
   DOSIK, H
   SHEIKHAI, M
   RYANS, P
   SOUFFRANT, H
   PRCHAL, J
   BRADDOCK, J
   MCARDLE, T
   CARLOS, T
   SCHMOTZER, A
   GARDNER, D
   MOORE, R
   DOVER, G
   BERGNER, M
   EWART, C
   ECKERT, S
   LENT, C
   ULRICH, J
   FISHPAW, L
   TIRADO, G
   GIBSON, J
   MOELLER, T
   NAGEL, T
   TERRIN, M
   HANDY, C
   HARRIS, D
   CANNER, M
   DEPKIN, J
   MEINERT, N
   CARROLL, M
   GIRO, R
   KARABELAS, S
   KELLY, C
   HEYMAN, M
   BEILINSON, P
   DRUSKIN, M
   ELLIS, P
   FLOOD, WA
   KRAVITZ, S
   LANZKRON, S
   LORICA, V
   MOLITERNO, A
   NAHUM, A
   NESBITT, JA
   ROSENTHAL, L
   SHARFMAN, W
   STREIFF, M
   WACHSMAN, M
   BRAY, P
   VANDANG, C
   CASELLA, J
   MCGUIRE, M
   PATRICK, L
   SCHAAD, H
   STEINER, C
   JOHNSON, C
   BANK, A
   CUTTER, G
   DAVIS, CE
   HUNTLEY, O
   LESSIN, L
   PLATT, O
   GRAYSECUNDY, M
   BONDS, D
   REID, C
   GELLER, H
   WACLAWIW, M
AF CHARACHE, S
   TERRIN, ML
   MOORE, RD
   DOVER, GJ
   BARTON, FB
   ECKERT, SV
   MCMAHON, RP
   BONDS, DR
   ORRINGER, E
   JONES, S
   STRAYHORN, D
   ROSSE, W
   PHILLIPS, G
   PEACE, D
   JOHNSONTELFAIR, A
   MILNER, P
   KUTLAR, A
   TRACY, A
   BALLAS, SK
   ALLEN, GE
   MOSHANG, J
   SCOTT, B
   STEINBERG, M
   ANDERSON, A
   SABAHI, V
   PEGELOW, C
   TEMPLE, D
   CASE, E
   HARRELL, R
   CHILDERIE, S
   EMBURY, S
   SCHMIDT, B
   DAVIES, D
   KOSHY, M
   TALISCHYZAHED, N
   DORN, L
   PENDARVIS, G
   MCGEE, M
   TELFER, M
   DAVIS, A
   CASTRO, O
   FINKE, H
   PERLIN, E
   SITEMAN, J
   GASCON, P
   DIPAOLO, P
   GARGIULO, S
   ECKMAN, J
   BAILEY, JH
   PLATT, A
   WALLER, L
   RAMIREZ, G
   KNORS, V
   HERNANDEZ, S
   RODRIGUEZ, EM
   WILKES, E
   VICHINSKY, E
   CLASTER, S
   EARLES, A
   KLEMAN, K
   MCLAUGHLIN, K
   SWERDLOW, P
   SMITH, W
   MADDOX, B
   USRY, L
   BRENNER, A
   WILLIAMS, K
   OBRIEN, R
   GENTHER, K
   SHURIN, S
   BERMAN, B
   CHIARUCCI, K
   KEVERLINE, L
   OLIVIERI, N
   SHAW, D
   LEWIS, N
   BRIDGES, K
   TYNAN, B
   WINOGRAD, C
   BELLEVUE, R
   DOSIK, H
   SHEIKHAI, M
   RYANS, P
   SOUFFRANT, H
   PRCHAL, J
   BRADDOCK, J
   MCARDLE, T
   CARLOS, T
   SCHMOTZER, A
   GARDNER, D
   MOORE, R
   DOVER, G
   BERGNER, M
   EWART, C
   ECKERT, S
   LENT, C
   ULRICH, J
   FISHPAW, L
   TIRADO, G
   GIBSON, J
   MOELLER, T
   NAGEL, T
   TERRIN, M
   HANDY, C
   HARRIS, D
   CANNER, M
   DEPKIN, J
   MEINERT, N
   CARROLL, M
   GIRO, R
   KARABELAS, S
   KELLY, C
   HEYMAN, M
   BEILINSON, P
   DRUSKIN, M
   ELLIS, P
   FLOOD, WA
   KRAVITZ, S
   LANZKRON, S
   LORICA, V
   MOLITERNO, A
   NAHUM, A
   NESBITT, JA
   ROSENTHAL, L
   SHARFMAN, W
   STREIFF, M
   WACHSMAN, M
   BRAY, P
   VANDANG, C
   CASELLA, J
   MCGUIRE, M
   PATRICK, L
   SCHAAD, H
   STEINER, C
   JOHNSON, C
   BANK, A
   CUTTER, G
   DAVIS, CE
   HUNTLEY, O
   LESSIN, L
   PLATT, O
   GRAYSECUNDY, M
   BONDS, D
   REID, C
   GELLER, H
   WACLAWIW, M
TI EFFECT OF HYDROXYUREA ON THE FREQUENCY OF PAINFUL CRISES IN
   SICKLE-CELL-ANEMIA
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID FETAL HEMOGLOBIN; KINETICS; BABOONS; DISEASE
AB Background. In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises.
   Methods. In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months.
   Results. Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P<0.001). The median times to the first crisis (3.0 vs. 1.5 months, P=0.01) and the second crisis (8.8 vs. 4.6 months, P<0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs, 51, P<0.001), and fewer underwent transfusions (48 vs. 73, P=0.001). At the end of the study, the doses of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day. Treatment with hydroxyurea did not cause any important adverse effects.
   Conclusions. Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year, Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored, The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain.
C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD.
   MARYLAND MED RES INST,BALTIMORE,MD 21287.
   NHLBI,BETHESDA,MD 20892.
   UNIV N CAROLINA,CHAPEL HILL,NC.
   DUKE UNIV,DURHAM,NC.
   MED COLL GEORGIA,AUGUSTA,GA 30912.
   THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107.
   UNIV MISSISSIPPI,JACKSON,MS 39216.
   UNIV MIAMI,MIAMI,FL 33152.
   SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110.
   UNIV ILLINOIS,CHICAGO,IL.
   MICHAEL REESE HOSP & MED CTR,CHICAGO,IL 60616.
   HOWARD UNIV,WASHINGTON,DC 20059.
   UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103.
   EMORY UNIV,ATLANTA,GA 30322.
   ST LUKES ROOSEVELT HOSP,NEW YORK,NY.
   CHILDRENS HOSP OAKLAND,OAKLAND,CA.
   VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA.
   CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106.
   HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA.
   BRIGHAM & WOMENS HOSP,BOSTON,MA 02115.
   INTERFAITH MED CTR,BROOKLYN,NY.
   UNIV ALABAMA,BIRMINGHAM,AL.
   UNIV PITTSBURGH,PITTSBURGH,PA.
RI McMahon, Robert/C-5462-2009
FU NCRR NIH HHS [RR 00046]; NHLBI NIH HHS [UO1-HL45692, UO1-HL45696]
NR 37
TC 1180
Z9 1200
U1 9
U2 39
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 MAY 18
PY 1995
VL 332
IS 20
BP 1317
EP 1322
DI 10.1056/NEJM199505183322001
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA QX857
UT WOS:A1995QX85700001
PM 7715639
ER

PT J
AU CHROUSOS, GP
AF CHROUSOS, GP
TI SEMINARS IN MEDICINE OF THE BETH-ISRAEL-HOSPITAL, BOSTON - THE
   HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE-MEDIATED INFLAMMATION
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID CORTICOTROPIN-RELEASING HORMONE; TUMOR-NECROSIS-FACTOR; SUSCEPTIBLE
   LEWIS RATS; CENTRAL NERVOUS-SYSTEM; RHEUMATOID-ARTHRITIS; MESSENGER-RNA;
   STIMULATED ADRENOCORTICOTROPIN; ARGININE-VASOPRESSIN; SUBSTANCE-P;
   T-CELLS
RP CHROUSOS, GP (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA.
NR 133
TC 1563
Z9 1606
U1 4
U2 32
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 MAY 18
PY 1995
VL 332
IS 20
BP 1351
EP 1362
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA QX857
UT WOS:A1995QX85700008
PM 7715646
ER

PT J
AU SCHECHTER, AN
   RODGERS, GP
AF SCHECHTER, AN
   RODGERS, GP
TI SICKLE-CELL-ANEMIA - BASIC RESEARCH REACHES THE CLINIC
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID HEMOGLOBIN; AUGMENTATION; HYDROXYUREA; DISEASE
RP SCHECHTER, AN (reprint author), NIDDKD,BETHESDA,MD 20892, USA.
OI Schechter, Alan N/0000-0002-5235-9408
NR 13
TC 27
Z9 28
U1 0
U2 1
PU MASS MEDICAL SOC
PI BOSTON
PA 10 SHATTUCK, BOSTON, MA 02115
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 18
PY 1995
VL 332
IS 20
BP 1372
EP 1374
DI 10.1056/NEJM199505183322010
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA QX857
UT WOS:A1995QX85700010
PM 7536300
ER

PT J
AU LORENZI, MV
   LONG, JE
   MIKI, T
   AARONSON, SA
AF LORENZI, MV
   LONG, JE
   MIKI, T
   AARONSON, SA
TI EXPRESSION CLONING, DEVELOPMENTAL EXPRESSION AND CHROMOSOMAL
   LOCALIZATION OF FIBROBLAST GROWTH FACTOR-VIII
SO ONCOGENE
LA English
DT Note
DE GROWTH FACTORS; FGF-8; AIGF; EXPRESSION CLONING
ID CDNA CLONING; FACTOR-I; FAMILY; GENE; PROTEIN; TRANSFORMATION;
   RECEPTORS; SEQUENCE; MEMBER; CELLS
AB A mouse testis cDNA library in lambda pCEV27 eukaryotic expression vector was transfected in NIH3T3 fibroblasts and several transformed foci were identified. A plasmid with high-titered focus forming activity was rescued from one of these transformants. Structural analysis of this cDNA predicted a protein identical to androgen induced growth factor (AIGF), recently identified as the eighth member of the fibroblast growth factor (FGF) family, A 1.6 kiIobasepair transcript of the FGF-8 gene was detected in testis but not in other adult tissues analysed. During development, expression of FGF-8 was restricted to embryonic days 9 through 13 suggesting that the growth factor plays a role during a discrete stage of mouse embryogenesis, An exon-containing genomic clone of human FGF-8 was isolated and structural comparisons indicated that the gene structure of this region is highly conserved among the FGF genes. Using a panel of human-rodent somatic cell hybrids, the FGF-8 gene was localized to human chromosome 10.
C1 MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029.
   NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892.
NR 29
TC 42
Z9 43
U1 0
U2 0
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAY 18
PY 1995
VL 10
IS 10
BP 2051
EP 2055
PG 5
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA QZ926
UT WOS:A1995QZ92600019
PM 7761105
ER

PT J
AU COPUR, S
   AIBA, K
   DRAKE, JC
   ALLEGRA, CJ
   CHU, E
AF COPUR, S
   AIBA, K
   DRAKE, JC
   ALLEGRA, CJ
   CHU, E
TI THYMIDYLATE SYNTHASE GENE AMPLIFICATION IN HUMAN COLON-CANCER CELL-LINES
   RESISTANT TO 5-FLUOROURACIL
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE THYMIDYLATE SYNTHASE; GENE AMPLIFICATION; 5-FU RESISTANCE
ID HUMAN-BREAST; DNA; 5-FLUORO-2'-DEOXYURIDINE; METHOTREXATE; SYNTHETASE;
   CARCINOMA; RNA; 5-FLUORODEOXYURIDINE; ADENOCARCINOMAS; MECHANISMS
AB A series of 5-fluorouracil (5-FU)-resistant human colon H630 cancer cell lines were established by continuous exposure of cells to 5-FU. The concentration of 5-FU required to inhibit cell proliferation by 50% (IC50) in the parent colon line (H630) was 5.5 mu M. The 5-FU IC50 values for the resistant H630-R1, H630-R10, and H630-R cell lines were 11-, 29-, and 27-fold higher than that for the parent H630 cell line. Using both the radioenzymatic 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) binding and catalytic assays for measurement of thymidylate synthase (TS) enzyme activity, there was significantly increased TS activity in resistant H630-R1 (13- and 23-fold), H630-R10 (37- and 40-fold), and H630-R (24- and 34-fold) lines, for binding and catalytic assays, respectively, compared with the parent H630 line. The level of TS protein, as determined by western immunoblot analysis, was increased markedly in resistant H630-R1 (23-fold), H630-R10 (33-fold), and H630-R (26-fold) cells. Northern analysis revealed elevations in TS mRNA levels in H630-R1 (18-fold), H630-R10 (39-fold), and H630-R (36-fold) cells relative to parent H630 cells. Although no major rearrangements of the TS gene were noted by Southern analysis, there was significant amplification of the TS gene in 5-FU-resistant cells, which was confirmed by DNA slot blot analysis. These studies demonstrate that continuous exposure of human colon cancer cells to 5-FU leads to TS gene amplification and overexpression of TS protein with resultant development of fluoropyrimidine resistance.
C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889.
   JAPANESE FDN CANC RES,CTR CANC CHEMO,TOKYO,JAPAN.
NR 44
TC 142
Z9 146
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD MAY 17
PY 1995
VL 49
IS 10
BP 1419
EP 1426
DI 10.1016/0006-2952(95)00067-A
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA RA124
UT WOS:A1995RA12400011
PM 7763285
ER

PT J
AU GUPTA, M
   FUJIMORI, A
   POMMIER, Y
AF GUPTA, M
   FUJIMORI, A
   POMMIER, Y
TI EUKARYOTIC DNA TOPOISOMERASES-I
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
LA English
DT Review
DE DNA TOPOISOMERASE; CANCER CHEMOTHERAPY; CAMPTOTHECIN; RECOMBINATION
ID SIMIAN VIRUS-40 DNA; ACTIVE-SITE TYROSINE; SINGLE-STRANDED-DNA;
   PROTEIN-KINASE-C; P-GLYCOPROTEIN EXPRESSION; NICKING-CLOSING ENZYME;
   HAMSTER OVARY CELLS; RNA POLYMERASE-II; HEAT-SHOCK GENES;
   ESCHERICHIA-COLI
C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892.
NR 182
TC 266
Z9 274
U1 2
U2 4
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 MAY 17
PY 1995
VL 1262
IS 1
BP 1
EP 14
DI 10.1016/0167-4781(95)00029-G
PG 14
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA RA119
UT WOS:A1995RA11900001
PM 7772596
ER

PT J
AU GRZESIEK, S
   KUBONIWA, H
   HINCK, AP
   BAX, A
AF GRZESIEK, S
   KUBONIWA, H
   HINCK, AP
   BAX, A
TI MULTIPLE-QUANTUM LINE NARROWING FOR MEASUREMENT OF H-ALPHA-H-BETA
   J-COUPLINGS IN ISOTOPICALLY ENRICHED PROTEINS
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PULSED-FIELD GRADIENTS; NMR-SPECTROSCOPY; CONSTANTS; SPECTRA; PHASE;
   C-13; H-1; RESONANCE; FILTERS; N-15
AB Uniform C-13 enrichment of proteins is commonly used for NMR studies of proteins that are not amenable to conventional homonuclear 2D NMR spectroscopy. In such studies, the one-bond H-1-C-13 dipolar interaction is usually the dominant source of H-1 line broadening. H-1-C-13 zero- and double-quantum coherences are, to first order, not affected by this dipolar relaxation mechanism. The relatively long relaxation time of such H-1(alpha)-C-13(alpha) multiple-quantum coherences is exploited for measurement of H-alpha-H-beta J couplings in a sample of uniformly C-13-enriched calcium-free calmodulin (16.7 kD) and a sample of TGF-beta 1 (25 kDa). J(H-alpha-H-beta) provides information on the stereospecific resonance assignment for residues with nonequivalent H-beta methylene protons and on the chi(1) torsion angles.
C1 NIDR,STRUCT MOLEC BIOL UNIT,BETHESDA,MD 20892.
RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA.
NR 25
TC 125
Z9 125
U1 0
U2 4
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 MAY 17
PY 1995
VL 117
IS 19
BP 5312
EP 5315
DI 10.1021/ja00124a014
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA QY885
UT WOS:A1995QY88500014
ER

PT J
AU BOICE, JD
   TRAVIS, LB
AF BOICE, JD
   TRAVIS, LB
TI BODY WARS - EFFECT OF FRIENDLY FIRE (CANCER-THERAPY)
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID HODGKINS-DISEASE; MALIGNANCIES; LEUKEMIA; TUMORS; RISK
C1 NCI,DIV CANC ETIOL,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892.
NR 17
TC 8
Z9 8
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 MAY 17
PY 1995
VL 87
IS 10
BP 705
EP 706
DI 10.1093/jnci/87.10.705
PG 2
WC Oncology
SC Oncology
GA QX759
UT WOS:A1995QX75900002
PM 7563142
ER

PT J
AU KELLEY, MJ
   NAKAGAWA, K
   STEINBERG, SM
   MULSHINE, JL
   KAMB, A
   JOHNSON, BE
AF KELLEY, MJ
   NAKAGAWA, K
   STEINBERG, SM
   MULSHINE, JL
   KAMB, A
   JOHNSON, BE
TI DIFFERENTIAL INACTIVATION OF CDKN2 AND RB PROTEIN IN NON-SMALL-CELL AND
   SMALL-CELL LUNG-CANCER CELL-LINES
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID RETINOBLASTOMA SUSCEPTIBILITY GENE; P53 GENE; HOMOZYGOUS DELETIONS; RAS
   MUTATIONS; EXPRESSION; CARCINOMA; GROWTH; ABNORMALITIES; IDENTIFICATION;
   CHROMOSOME-3
AB Background: The CDKN2 gene encodes the human cyclin-dependent kinase 4 inhibitor. This inhibitor protein is believed to be a tumor suppressor that plays an essential role in cell cycle regulation. One half of all cancer cell lines and one fourth of lung cancer cell lines examined to date contain homozygous deletions (i.e., both alleles lost) of CDKN2. However, the relative frequency of homozygous CDKN2 deletions in non-small-cell lung cancers (NSCLC) and in small-cell lung cancers (SCLC) has not been determined. Inactivation or loss of another tumor suppressor encoded by the retinoblastoma gene (the Rb protein) is more common in SCLC than in NSCLC. Purpose: We measured the frequency of homozygous CDKN2 deletions in 77 NSCLC and in 93 SCLC tumor cell lines. In addition, possible associations were explored between CDKN2 gene loss, the presence or absence of Rb protein, and the clinical status of lung cancer patients. Methods: DNA was isolated from each tumor cell line and from the primary tumor and normal tissue of one NSCLC patient. Sequences corresponding to exons 1 and 2 of the CDKN2 gene were amplified by use of the polymerase chain reaction, and the resulting amplification products were analyzed by agarose gel electrophoresis and DNA blotting. Genomic DNA blotting was also used to evaluate CDKN2 gene deletions. The frequency of homozygous CDKN2 loss and the presence or absence of functional Rb protein (reported previously) in the cell lines were compared. Results: Homozygous deletion of CDKN2 was detected in 18 (23%) of 77 cell lines established from patients with NSCLC, compared with one (1%) of 93 cell lines established from patients with SCLC (P<.001). No CDKN2 gene loss was observed in the normal tissue of an NSCLC patient whose tumor cell line showed homozygous deletion of the gene; however, the primary tumor from this patient had evidence of CDKN2 loss. Homozygous CDKN2 deletion was detected in 13 (28%) of 46 tumor cell lines from patients with stage III or stage IV NSCLC, compared with zero of 10 tumor cell lines from patients with stage I or stage II NSCLC. Coincident loss of CDKN2 genes and functional Rb protein was rarely observed (in two of 135 cell lines). Conclusion: The frequency of homozygous CDKN2 gene deletion in NSCLC cell lines is greater than that observed for any other known, or candidate, tumor suppressor gene. Implication: Further study of the role of CDKN2 gene alteration in the pathogenesis of NSCLC is needed.
C1 NCI, DIV CANC TREATMENT, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA.
RP KELLEY, MJ (reprint author), NATL NAVAL MED CTR, NCI,NAVY MED ONCOL BRANCH,DIV CANC TREATMENT, BLDG 8, RM 5105, BETHESDA, MD 20889 USA.
OI Kelley, Michael/0000-0001-9523-6080
NR 47
TC 86
Z9 89
U1 0
U2 1
PU NATL CANCER INSTITUTE
PI BETHESDA
PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY 17
PY 1995
VL 87
IS 10
BP 756
EP 761
DI 10.1093/jnci/87.10.756
PG 6
WC Oncology
SC Oncology
GA QX759
UT WOS:A1995QX75900016
PM 7563154
ER

PT J
AU BHAT, MK
   MCPHIE, P
   CHENG, SY
AF BHAT, MK
   MCPHIE, P
   CHENG, SY
TI INTERACTION OF THYROID-HORMONE NUCLEAR RECEPTOR WITH ANTIBODY -
   CHARACTERIZATION OF THE THYROID-HORMONE BINDING-SITE
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; SECONDARY STRUCTURE; DOMAIN
AB To understand the structural basis in the hormone-dependent transcriptional regulation of human pi thyroid hormone receptor (h-TR beta 1), we characterized the region which interacted with the thyroid hormone, 3,3',5-triiodo-L-thyronine (T-3). Using the hormone binding domain of h-TR beta 1 (K-206-D-461) as an immunogen, we screened for monoclonal antibodies which inhibited the binding of T-3 to h-TR beta 1. mAb C3, which recognized native h-TR beta 1, was obtained. Analyses of the binding data indicate that binding of T-3 to h-TR beta 1 was competitively inhibited by mAb C3. Using a series of truncated mutants of h-TR beta 1 and synthetic peptides, we mapped the binding site of mAb C3 to the region of E(248)-V-256. Thus, part of T-3 binding site in h-TR beta 1 is in this nine-amino acid segment, which was shown by circular dichroism spectroscopy to be a random coil. Based on the proposed model of the hormone binding domain as an alpha/beta barrel, E(248)-V-256 contains part of Loop 1 which is on the same side of the DNA binding domain. These results raise the possibility that Loop 1 could be in direct contact with the nearby DNA binding domain to affect the interaction of DNA binding domain with the T-3 target genes. (C) 1995 Academic Press, Inc.
C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD.
   NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892.
NR 19
TC 12
Z9 12
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 MAY 16
PY 1995
VL 210
IS 2
BP 464
EP 471
DI 10.1006/bbrc.1995.1683
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA QX870
UT WOS:A1995QX87000032
PM 7538760
ER

PT J
AU NAKHAI, B
   NIELSEN, DA
   LINNOILA, M
   GOLDMAN, D
AF NAKHAI, B
   NIELSEN, DA
   LINNOILA, M
   GOLDMAN, D
TI 2 NATURALLY-OCCURRING AMINO-ACID SUBSTITUTIONS IN THE HUMAN 5-HT1A
   RECEPTOR - GLYCINE-22 TO SERINE-22 AND ISOLEUCINE-28 TO VALINE-28
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
ID GENE; HIPPOCAMPUS; EXPRESSION; SEROTONIN; CELLS; 5-HYDROXYTRYPTAMINE;
   NEURONS; RATS
AB The human 5-HT1A receptor was screened for naturally occurring mutations. The PCR product of the 5-HT1A receptor gene was digested with several restriction enzymes and evaluated by single-strand conformational polymorphism (SSCP) analysis. Comparison of the SSCP electrophoretic pattern with a restriction map of the 5-HT1A receptor allowed localization of the polymorphic sites facilitating their identification by sequence analysis. Two polymorphisms were identified in the human 5-HT1A receptor gene that altered amino acid composition. The polymorphisms encode amino acid substitutions in the 5-HT1A receptor of a glycine to serine at amino acid 22 and an isoleucine to valine at amino acid 28, respectively. Both polymorphisms alter the extracellular amino terminal domain of the 5-HT1A receptor. The polymorphic 5-HT1A alleles have been found in American and Finnish Caucasians and in native American Indians. This is the first report of a polymorphism in the human 5-HT1A receptor gene that alters the structure of the 5-HT1A receptor protein composition. (C) 1995 Academic Press, Inc.
RP NAKHAI, B (reprint author), NIAAA,NEUROGENET LAB,MOLEC GENET SECT,ROCKVILLE,MD 20852, USA.
RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
NR 20
TC 38
Z9 40
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAY 16
PY 1995
VL 210
IS 2
BP 530
EP 536
DI 10.1006/bbrc.1995.1692
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA QX870
UT WOS:A1995QX87000041
PM 7755630
ER

PT J
AU OHANLON, TP
   RABEN, N
   MILLER, FW
AF OHANLON, TP
   RABEN, N
   MILLER, FW
TI A NOVEL GENE ORIENTED IN A HEAD-TO-HEAD CONFIGURATION WITH THE HUMAN
   HISTIDYL-TRANSFER-RNA SYNTHETASE (HRS) GENE ENCODES AN MESSENGER-RNA
   THAT PREDICTS A POLYPEPTIDE HOMOLOGOUS TO HRS
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
ID TRANSFER-RNA-SYNTHETASE; BIDIRECTIONAL PROMOTER; EVOLUTIONARY
   RELATIONSHIPS; MESSENGER-RNA; RESTRICTION; ALPHA-1(IV); EXPRESSION; SITE
AB The human histidyl-tRNA synthetase (HRS) gene encodes an enzyme that catalyzes the esterification of histidine to its cognate tRNA as an early step in protein biosynthesis. Previous reports have described a bidirectional promoter element which coordinates the transcription of both HRS and an unknown mRNA whose gene is oriented in a head-to-head configuration with HRS. We have isolated and characterized a human genomic DNA clone that encodes portions of these oppositely transcribed mRNAs and a putatively full-length cDNA clone (HO3) corresponding to the gene mapping immediately 5' of HRS. The largest open reading frame within HO3 (1518 bp) shares approximately 75% nucleotide sequence identity with human HRS (1527 bp) and predicts a polypeptide with extensive amino acid sequence homology with the HRS protein (72%). Moreover, amino acid sequence motifs characteristic of class II aminoacyl-tRNA synthetases are conserved within HO3. Despite their similarity, HRS and HO3 have divergent amino-terminal domains which correspond to the first two exons of each gene. RNA blot analysis revealed that HRS (2.0 kb) and HO3 (2.5 kb) exhibit distinct patterns of steady-state mRNA expression among multiple human tissues. (C) 1995 Academic Press, Inc.
C1 NIAMSD,BETHESDA,MD 20892.
RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA.
NR 25
TC 26
Z9 28
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAY 16
PY 1995
VL 210
IS 2
BP 556
EP 566
DI 10.1006/bbrc.1995.1696
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA QX870
UT WOS:A1995QX87000045
PM 7755634
ER

PT J
AU GIUSTI, RM
   IWAMOTO, K
   HATCH, EE
AF GIUSTI, RM
   IWAMOTO, K
   HATCH, EE
TI DIETHYLSTILBESTROL REVISITED - A REVIEW OF THE LONG-TERM HEALTH-EFFECTS
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID CLEAR-CELL ADENOCARCINOMA; WOMEN EXPOSED INUTERO; GENITAL-TRACT CHANGES;
   FOLLOW-UP; TESTICULAR CANCER; RISK-FACTORS; YOUNG-WOMEN; BREAST-CANCER;
   STILBESTROL THERAPY; VAGINAL ADENOSIS
AB Purpose: To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed in utero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren).
   Data Sources: English-language articles were identified through MEDLINE and CANCERLIT searches and through review of the bibliographies of identified articles.
   Study Selection: All human studies relevant to longterm health effects of exposure to DES were reviewed.
   Data Extraction: Descriptive data on existing DES cohorts were extracted from early publications. Risk estimates for health effects were extracted from published reports.
   Data Synthesis: An estimated 5 to 10 million Americans received DES during pregnancy or were exposed to the drug in utero. Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, <2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10 000. The association between DES exposure and testicular cancer in DES sons remains controversial. Exposure to DES has also been linked to reproductive tract abnormalities in DES sons and daughters that consist of immune system disorders and psychosexual effects. No evidence for transgenerational effects currently exists. Recommendations for screening persons exposed to DES are reviewed.
   Conclusions: Further research is needed to define long-term health effects related to DES exposure. Such research would provide a basis for counseling persons exposed to DES and would further understanding of environmental and pharmacologic compounds similar to DES.
RP GIUSTI, RM (reprint author), NCI,DIV CANC TREATMENT,OFF DIRECTOR,BLDG 31,ROOM 3A44,BETHESDA,MD 20892, USA.
NR 112
TC 248
Z9 259
U1 5
U2 20
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 15
PY 1995
VL 122
IS 10
BP 778
EP 788
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA QX147
UT WOS:A1995QX14700008
PM 7717601
ER

PT J
AU KIM, YO
   OH, IU
   PARK, HS
   JENG, JJ
   SONG, BJ
   HUH, TL
AF KIM, YO
   OH, IU
   PARK, HS
   JENG, JJ
   SONG, BJ
   HUH, TL
TI CHARACTERIZATION OF A CDNA CLONE FOR HUMAN NAD(+)-SPECIFIC ISOCITRATE
   DEHYDROGENASE ALPHA-SUBUNIT AND STRUCTURAL COMPARISON WITH ITS
   ISOENZYMES FROM DIFFERENT SPECIES
SO BIOCHEMICAL JOURNAL
LA English
DT Article
ID PIG-HEART; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; BINDING PROTEINS;
   CALCIUM-IONS; PHOSPHORYLATION; EXPRESSION; SEQUENCES; NAD; RAT
AB A 0.6 kb cDNA fragment encoding the human NAD(+)-specific isocitrate dehydrogenase alpha-subunit (H-IDH alpha) was amplified by PCR using oligonucleotide primers synthesized on the basis of pig tryptic peptide sequences [Huang and Colman (1990) Biochemistry 29, 8266-8273]. With the amplified cDNA as a probe, cDNA clones for IDH alpha were isolated from a human heart lambda gt11 cDNA library, The deduced protein sequence of the largest cDNA clone (2628 bp) rendered a precursor protein of 366 amino acids (39 591 Dal and a mature protein of 339 amino acids (36640 Dal. The deduced H-IDH alpha protein sequence is highly similar to the partial peptide sequences of the pig enzyme, It is 55, 43 and 44% identical with yeast NAD(+)-specific IDH2, yeast NAD(+)-specific IDH1 and monkey NAD(+)-specific IDH gamma-subunit (IDH gamma) respectively. However, it has less similarity (about 3.0%) to NADP(+)-specific IDH from Escherichia coli and bovine mitochondria. These results indicate that the structure of IDH alpha closely resembles that of IDH2, the catalytic subunit of the yeast enzyme, Structural analysis of the deduced H-IDH alpha protein revealed that the amino acids responsible for the binding of isocitrate, Mg2+ and NAD are highly conserved, It also has two conserved motifs for the binding sites of ATP and ADP, but a canonical Ca2+-binding motif was not recognized. Unusual penta- (ATTTA) and tri-(TAA or ATT) nucleotides which are respectively believed to interact with RNA-binding proteins and be near the endonuclease cleavage sites were frequently recognized in its 3' untranslated region, indicating the possibility of an additional method of regulation of this enzyme. Northern-blot analysis suggests that one mRNA transcript (2.8 kb) exists in cultured HeLa cells. Genomic DNA Southern-blot analysis indicates that the IDH alpha gene is not closely related to that of the other IDH isoenzymes, and IDH alpha appears to be encoded by a single gene.
C1 KYUNGPOOK NATL UNIV,COLL NAT SCI,DEPT GENET ENGN,TAEGU 702701,SOUTH KOREA.
   HYOSUNG WOMENS UNIV,DEPT PLANT BREEDING & GENET,KYUNGPOOK 713702,SOUTH KOREA.
   NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852.
NR 44
TC 28
Z9 30
U1 2
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 MAY 15
PY 1995
VL 308
BP 63
EP 68
PN 1
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ913
UT WOS:A1995QZ91300009
PM 7755589
ER

PT J
AU GARCIABORREGUERO, D
   JACOBSEN, FM
   MURPHY, DL
   JOSEPHVANDERPOOL, JR
   CHIARA, A
   ROSENTHAL, NE
AF GARCIABORREGUERO, D
   JACOBSEN, FM
   MURPHY, DL
   JOSEPHVANDERPOOL, JR
   CHIARA, A
   ROSENTHAL, NE
TI HORMONAL RESPONSES TO THE ADMINISTRATION OF M-CHLOROPHENYLPIPERAZINE IN
   PATIENTS WITH SEASONAL AFFECTIVE-DISORDER AND CONTROLS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE SEASONAL AFFECTIVE DISORDER (SAD), M-CHLOROPHENYLPIPERAZINE (M-CPP)
   SEROTONIN, LIGHT THERAPY, PROLACTIN, CORTISOL
ID AGONIST META-CHLOROPHENYLPIPERAZINE; SEROTONIN AGONIST; NEURO-ENDOCRINE;
   CIRCANNUAL RHYTHMS; HEALTHY-SUBJECTS; LIGHT THERAPY; PROLACTIN; RAT;
   5-HYDROXYTRYPTOPHAN; NEUROENDOCRINE
AB We report on the plasma cortisol and prolactin responses to the serotonergic agonist m-CPP (0.1 mg/kg) in 10 patients with winter seasonal affective disorder (SAD) and 10 controls during the winter, in both untreated and bright light-treated conditions; and on 8 other SAD patients and 8 other controls during the summer, Following m-CPP infusion, untreated patients had exaggerated prolactin (p < .05) and cortisol (p < .05) responses compared to controls. Light treatment significantly reduced responses of both hormones to m-CPP (prolactin: p < .01; cortisol: p < .01), When untreated winter subjects and summer subjects were compared, cortisol, bur not prolactin responses to m-CPP were found to be higher in patients than in controls during the winter, and lower in patients than in controls during the summer (diagnosis by season: p < .05), These results are consistent with those of our previous report on the behavioral responses to m-CPP in the same patients and suggest an abnormality in serotonergic function in untreated SAD patients in winter, which is normalized following treatment with light therapy and naturally during the summer.
C1 NIMH,CLIN PSYCHOBIOL BRANCH,CLIN SCI LAB,BETHESDA,MD 20892.
NR 61
TC 34
Z9 35
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 15
PY 1995
VL 37
IS 10
BP 740
EP 749
DI 10.1016/0006-3223(94)00208-K
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QW650
UT WOS:A1995QW65000007
PM 7640329
ER

PT J
AU OTSUKI, T
   YANO, T
   CLARK, HM
   BASTARD, C
   KERCKAERT, JP
   JAFFE, ES
   RAFFELD, M
AF OTSUKI, T
   YANO, T
   CLARK, HM
   BASTARD, C
   KERCKAERT, JP
   JAFFE, ES
   RAFFELD, M
TI ANALYSIS OF LAZ3 (BCL-6) STATUS IN B-CELL NON-HODGKINS-LYMPHOMAS -
   RESULTS OF REARRANGEMENT AND GENE-EXPRESSION STUDIES AND A MUTATIONAL
   ANALYSIS OF CODING REGION SEQUENCES
SO BLOOD
LA English
DT Article
ID HUMAN FOLLICULAR LYMPHOMA; FINGER ENCODING GENE; BAND 3Q27;
   TRANSLOCATIONS; CLONING; ONCOGENE; LOCUS
AB The LAZ3 gene encodes a novel zinc-finger protein that shares homology with several Drosophila transcription factors. This gene was identified by its disruption in translocations involving chromosome 3q27 in diffuse large-cell lymphomas. To assess the frequency and role of this gene's involvement in lymphomagenesis and tumor progression, we examined a series of 170 cases of non-Hodgkin's lymphomas of B-cell lineage for LAZ3 gene rearrangement, expression, and mutation. The cases included 35 de novo diffuse aggressive lymphomas (DAL; 19 large-cell, 4 mixed-cell, and 12 large-cell immunoblastic), 52 transformed aggressive lymphomas derived from follicular lymphomas (TFL), 42 indolent follicular lymphomas (FL), 14 mantle cell lymphomas (MCL), and 27 small noncleaved cell lymphomas (SNCL). LAZ3 rearrangements were found in 10 DAL (28.6%), 9 TFL (17.3%), and 6 FL (14.3%), but not in any of the SNCL or MCL. LAZ3 rearrangement was not exclusive of bcl-2 rearrangement. Most rearrangement breakpoints mapped to a 10-kb BamHI-Xba I fragment located 5' to the LAZ3 coding sequence, consistent with previously reported breakpoint locations. Northern analysis of both rearranged and nonrearranged B-cell lymphoma cases showed similar levels of a transcript of approximately 3.8 kb, indicating that LAZ3 is broadly expressed in B-cell tumors and is not confined to rearranged cases. To investigate whether mutation of the LAZ3 gene might contribute to a potential role for this gene in lymphomagenesis, we screened the coding sequences of 13 rearranged cases, 6 nonrearranged cases, and 13 hematopoietic tumor cell lines. Although three probable polymorphisms were identified, mutations were detected in only 2 rearranged cases. Only 1 of these resulted in an amino acid substitution. Two cell lines (SU-DHL4 and Molt-4) also contained mutations; only one resulted in an amino acid substitution. We conclude (1) that LAZ3 rearrangements occur in a significant fraction of de novo DAL as well as in a smaller subset of indolent and transformed follicular lymphomas; (2) that LAZ3 message is expressed in both rearranged and nonrearranged B-cell lymphomas; and (3) that mutation of the LAZ3 gene does not contribute to its putative oncogenic role in most 3q27 translocated B-cell lymphomas. (C) 1995 by The American Society of Hematology.
C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892.
   CTR REG TRANSFUS SANGUINE,DEPT CYTOGENET,BOIS GUILLAUME,FRANCE.
   INST RECH CANC,INSERM,U124,LILLE,FRANCE.
NR 30
TC 111
Z9 112
U1 0
U2 1
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0006-4971
J9 BLOOD
JI Blood
PD MAY 15
PY 1995
VL 85
IS 10
BP 2877
EP 2884
PG 8
WC Hematology
SC Hematology
GA QX866
UT WOS:A1995QX86600032
PM 7742550
ER

PT J
AU FIBACH, E
   KOLLIA, P
   SCHECHTER, AN
   NOGUCHI, CT
   RODGERS, GP
AF FIBACH, E
   KOLLIA, P
   SCHECHTER, AN
   NOGUCHI, CT
   RODGERS, GP
TI HEMIN-INDUCED ACCELERATION OF HEMOGLOBIN PRODUCTION IN IMMATURE CULTURED
   ERYTHROID-CELLS - PREFERENTIAL ENHANCEMENT OF FETAL HEMOGLOBIN
SO BLOOD
LA English
DT Article
ID FRIEND-ERYTHROLEUKEMIA CELLS; GAMMA-GLOBIN SYNTHESIS; BETA-THALASSEMIA;
   TRANSFERRIN RECEPTOR; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; FERRITIN
   CONTENT; LIQUID CULTURE; COLONY GROWTH; MESSENGER-RNA
AB The effects of heme, when added as the ferric chloride salt, hemin, on human erythroid cells grown in a two-phase liquid culture system were studied. When added together with erythropoietin, on initiation of the second phase of the culture, hemin greatly accelerated hemoglobin (Hb) accumulation in these cells. The effect was greater during their early stages of maturation, suggesting that heme availability is then a rate-limiting step for Hb synthesis. Hemin increased preferentially the production of fetal Hb (HbF) compared with adult Hb; this was associated with a selective twofold elevation in gamma-mRNA levels. Using succinylacetone, a potent inhibitor of heme synthesis, we showed that exogenously supplied hemin could be incorporated into the de novo formed Hb. Therefore, the mechanism of hemin action may be severalfold, including effects on globin gene transcription and posttranslational events, eg, supplying the prosthetic group for Hb assembly. Hemin increased HbF of cells derived from patients with sickle cell anemia and beta-thalassemia as well as that of cells from normal donors. Moreover, when added in combination with other HbF-augmenting agents such as the cytotoxic drug, hydroxyurea, a synergistic effect was obtained, with considerably less cytotoxicity than with hydroxyurea alone. These results have clinical potential in light of the ameliorating effect that increased HbF has in patients with genetic diseases of the beta-globin chain and raise the possibility of combined treatment with hemin and other drugs now being used to treat these diseases. (C) 1995 by The American Society of Hematology.
C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL.
RP FIBACH, E (reprint author), NIDDK,BIOL CHEM LAB,BLDG 10,ROOM 9N-312,10 CTR DR,MSC 1822,BETHESDA,MD 20892, USA.
OI Schechter, Alan N/0000-0002-5235-9408
NR 59
TC 52
Z9 52
U1 0
U2 1
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0006-4971
J9 BLOOD
JI Blood
PD MAY 15
PY 1995
VL 85
IS 10
BP 2967
EP 2974
PG 8
WC Hematology
SC Hematology
GA QX866
UT WOS:A1995QX86600042
PM 7537986
ER

PT J
AU ICHIKAWA, H
   DEGUCHI, T
   NAKAGO, T
   JACOBOWITZ, DM
   SUGIMOTO, T
AF ICHIKAWA, H
   DEGUCHI, T
   NAKAGO, T
   JACOBOWITZ, DM
   SUGIMOTO, T
TI PARVALBUMIN-IMMUNOREACTIVE AND CALRETININ-IMMUNOREACTIVE TRIGEMINAL
   NEURONS INNERVATING THE RAT MOLAR TOOTH-PULP
SO BRAIN RESEARCH
LA English
DT Article
DE PARVALBUMIN; CALRETININ; TRIGEMINAL GANGLION; TOOTH PULP; RAT
ID GENE-RELATED PEPTIDE; CARBONIC-ANHYDRASE ACTIVITY; DORSAL-ROOT GANGLIA;
   VASOACTIVE INTESTINAL POLYPEPTIDE; PRIMARY SENSORY NEURONS; P-LIKE
   IMMUNOREACTIVITY; CENTRAL NERVOUS-SYSTEM; SUBSTANCE-P;
   IMMUNOHISTOCHEMICAL LOCALIZATION; HORSERADISH-PEROXIDASE
AB Calcium-binding proteins and neuropeptides were examined in trigeminal neuronal cell bodies retrogradely labeled with Fast blue (FB) from the maxillary molar tooth pulp of the rat. FB-labeled cells were located in the maxillary division of the trigeminal ganglion. similar to 30 and 50% of the labeled cells were immunoreactive for parvalbumin and calcitonin gene-related peptide (CGRP), respectively. The coexpression of these substances was observed in 9.5% of FB-labeled cells. On the other hand, 2.4% of FB-labeled cells exhibited calretinin-immunoreactivity (CR-ir) and 20% tachykinin (TK)-ir. The coexpression of CR and TK was observed in 1.9% of FB-labeled cells, i.e., most of CR-ir FB-labeled neurons coexpressed TK-ir. An immuno-EM method revealed that all parvalbumin-ir nerve fibers in the root pulp were myelinated and that CGRP-ir nerve fibers were both myelinated (15%) and unmyelinated (85%). The present study indicated that primary nociceptors innervating the rat molar tooth pulp contained parvalbumin and CR and coexpressed these calcium-binding proteins and neuropeptides. It was suggested that peripheral axons of parvalbumin-ir tooth pulp primary neurons are all myelinated. Most peripheral CR-ir axons are probably unmyelinated because TK-ir myelinated axons have never been demonstrated in any peripheral organ.
C1 OKAYAMA UNIV,SCH DENT,DEPT ORTHODONT,OKAYAMA 700,JAPAN.
   NIMH,CLIN SCI LAB,BETHESDA,MD 20892.
RP ICHIKAWA, H (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN.
NR 41
TC 39
Z9 40
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 MAY 15
PY 1995
VL 679
IS 2
BP 205
EP 211
DI 10.1016/0006-8993(95)00234-H
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA QZ290
UT WOS:A1995QZ29000003
PM 7633881
ER

PT J
AU TABAR, L
   FAGERBERG, G
   CHEN, HH
   DUFFY, SW
   SMART, CR
   GAD, A
   SMITH, RA
AF TABAR, L
   FAGERBERG, G
   CHEN, HH
   DUFFY, SW
   SMART, CR
   GAD, A
   SMITH, RA
TI EFFICACY OF BREAST-CANCER SCREENING BY AGE - NEW RESULTS FROM THE
   SWEDISH 2-COUNTY TRIAL
SO CANCER
LA English
DT Article
DE BREAST CANCER; BREAST SCREENING; AGE-SPECIFIC EFFECTS; SOJOURN TIME;
   INTERSCREENING INTERVAL
ID DEATH RATES; WOMEN; MAMMOGRAPHY; MORTALITY; DIAGNOSIS; SURVIVAL; MODELS
AB Background. Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women. Various possible reasons have been suggested for this, but none firmly is established.
   Methods. The Swedish Two-County Study is a randomized trial of breast cancer screening of women aged 40-74 years, comprising with 133,065 women with a 13-year follow-up of 2467 cancers. The Breast Cancer Detection Demonstration Project (BCDDP) is a nonrandomized screening program in the United States, with a 14-year follow-up of 3778 cancers in women aged 40-74 years. The Swedish results by age were updated. The lesser effect of screening at ages 40-49 years was investigated in terms of sojourn time (the duration of the preclinical but detectable phase) size, lymph node status, and histologic type of the tumors diagnosed in the Swedish Study and their subsequent effect on survival using survival data from both studies.
   Results. In the Swedish Trial, a 30% reduction in mortality associated with the invitation to screening of women aged 40-74 years was maintained after 13-years of follow-up. The reduction was 34% for women aged 50-74 years and 13% for women aged 40-49 years. Results indicated that the reduced effect on mortality far women aged 40-49 years was due to a differential effect of screening on the prognostic factors of tumor size, lymph node status, and histologic type. The mean sojourn times in the age groups 40-49 years, 50-59 years, 60-69 years, and 70-74 years were 1.7, 3.3, 3.8, and 2.6 years, respectively.
   Conclusions, These results suggest that much, although not all, of the smaller effect of screening on mortality in women aged 40-49 years is due to faster progression of a substantial proportion of tumors in this age group and the rapid increase in incidence during this decade of life. It is concluded that the interval between screenings should be shortened to achieve a greater benefit in this age group. It is estimated that a 19% reduction in mortality would result from an annual screening regime.
C1 LINKOPING UNIV HOSP,DEPT RADIOL,LINKOPING,SWEDEN.
   UNIV CAMBRIDGE,DEPT COMMUNITY MED,CAMBRIDGE,ENGLAND.
   MRC,BIOSTAT UNIT,CAMBRIDGE,ENGLAND.
   NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892.
   CENT HOSP FALUN,DEPT PATHOL,S-79182 FALUN,SWEDEN.
   AMER CANC SOC INC,ATLANTA,GA.
RP TABAR, L (reprint author), CENT HOSP FALUN,DEPT MAMMOG,S-79182 FALUN,SWEDEN.
OI Chen, Hsiu-Hsi/0000-0002-5799-6705
NR 28
TC 383
Z9 387
U1 2
U2 17
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 MAY 15
PY 1995
VL 75
IS 10
BP 2507
EP 2517
DI 10.1002/1097-0142(19950515)75:10<2507::AID-CNCR2820751017>3.0.CO;2-H
PG 11
WC Oncology
SC Oncology
GA QX652
UT WOS:A1995QX65200016
PM 7736395
ER

PT J
AU GOLDWASSER, F
   BAE, I
   VALENTI, M
   TORRES, K
   POMMIER, Y
AF GOLDWASSER, F
   BAE, I
   VALENTI, M
   TORRES, K
   POMMIER, Y
TI TOPOISOMERASE I-RELATED PARAMETERS AND CAMPTOTHECIN ACTIVITY IN THE
   COLON-CARCINOMA CELL-LINES FROM THE NATIONAL-CANCER-INSTITUTE ANTICANCER
   SCREEN
SO CANCER RESEARCH
LA English
DT Article
ID HAMSTER DC3F CELLS; DNA TOPOISOMERASE; CATALYTIC ACTIVITY; STRAND
   BREAKS; L1210 CELLS; PHASE-I; INHIBITOR; CLONING; CDNA;
   POLY(ADP-RIBOSYLATION)
AB Camptothecin (CPT) derivatives are a new family of anticancer agents which are selective inhibitors of DNA topoisomerase I (top1) and have entered clinical trials with promising results. The cellular determinants for CPT activity were studied in the seven cell lines of the National Cancer Institute anticancer screen. These cell lines exhibit natural differences in sensitivity to CPT and can be divided into three groups, according to their increasing resistance: colo205, SW620, HCT116<HT29, HCC2998<HCT15, and KM12. The differential sensitivity range was approximately 17-fold between KM12 and colo205 cells. CPT uptake varied only by less than a factor of three among the cell lines. Top1 mRNA, measured by Northern blotting analysis, and top1 protein levels, measured by Western blotting, varied by 2-fold or less among the cell Lines and were correlated neither with the CPT cytotoxicity nor the levels of cleavable complexes measured by alkaline elution in the various cell lines. An overall log-linear correlation was observed between CPT-induced top1-cleavable complexes and growth inhibition, indicating the importance of cleavable complex formation rather than top1 levels for cell killing in this panel of cell lines. Also, some cell lines displayed marked growth inhibition differences with minimal differences in cleavable complexes and S-phase fraction, suggesting that parameters downstream from the cleavable complexes are also critical for CPT cytotoxicity.
C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL DTP LAB,DNA TOPOL SECT,BETHESDA,MD 20892.
NR 51
TC 146
Z9 148
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 MAY 15
PY 1995
VL 55
IS 10
BP 2116
EP 2121
PG 6
WC Oncology
SC Oncology
GA QX367
UT WOS:A1995QX36700023
PM 7743511
ER

PT J
AU BORNER, MM
   MYERS, CE
   SARTOR, O
   SEI, Y
   TOKO, T
   TREPEL, JB
   SCHNEIDER, E
AF BORNER, MM
   MYERS, CE
   SARTOR, O
   SEI, Y
   TOKO, T
   TREPEL, JB
   SCHNEIDER, E
TI DRUG-INDUCED APOPTOSIS IS NOT NECESSARILY DEPENDENT ON
   MACROMOLECULAR-SYNTHESIS OR PROLIFERATION IN THE P53-NEGATIVE HUMAN
   PROSTATE-CANCER CELL-LINE PC-3
SO CANCER RESEARCH
LA English
DT Article
ID DNA STRAND BREAKS; ANTICANCER DRUGS; CHEMOTHERAPEUTIC-AGENTS;
   PROTEIN-SYNTHESIS; TOPOISOMERASE-II; C-MYC; THYMOCYTE APOPTOSIS;
   THYMINELESS DEATH; ANDROGEN ABLATION; RAT PROSTATE
AB The propensity of a cell to undergo apoptosis has been proposed to be a determinant for chemotherapy sensitivity that is not directly dependent on specific drug-target interactions. Androgen-independent prostate cancer is typically refractory to cytotoxic drugs, and we tested whether this is due to a loss of the ability to undergo apoptosis. Exposure of the hormone-insensitive and p53-negative human prostate carcinoma cell line PC-3 to 22 mu M cisplatin, 1 mu M camptothecin, 10 mu M tenoposide, 135 nM vincristine, or 10 mu M lovastatin for 72 h caused cell death, internucleosomal DNA fragmentation, and morphological changes typical for apoptosis. One mu M cycloheximide prevented anticancer drug-induced apoptosis, whereas high concentration (1 mM) of cycloheximide alone induced apoptosis, indicating that protein synthesis was not needed for these cells to undergo apoptosis. Since cycloheximide affected DNA synthesis and proliferation of PC-3 cells, we tested whether the DNA polymerase inhibitor aphidicolin could also suppress drug-induced apoptosis. In contrast to cycloheximide, aphidicolin inhibited only vincristine-induced apoptosis. Cycloheximide prevented drug-induced changes in cell cycle distribution except for vincristine, while aphidicolin led to an accumulation of cells at the G(1)-S border independent of the drug used. These data indicate that macromolecular synthesis, active cell cycling, and p53 expression are not required for apoptosis to proceed in this system.
C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892.
   NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892.
   NCI,MED BRANCH,BETHESDA,MD 20892.
RI Borner, Markus/B-7583-2011
NR 68
TC 115
Z9 117
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 MAY 15
PY 1995
VL 55
IS 10
BP 2122
EP 2128
PG 7
WC Oncology
SC Oncology
GA QX367
UT WOS:A1995QX36700024
PM 7743512
ER

PT J
AU BECKNER, ME
   KRUTZSCH, HC
   STRACKE, ML
   WILLIAMS, ST
   GALLARDO, JA
   LIOTTA, LA
AF BECKNER, ME
   KRUTZSCH, HC
   STRACKE, ML
   WILLIAMS, ST
   GALLARDO, JA
   LIOTTA, LA
TI IDENTIFICATION OF A NEW IMMUNOGLOBULIN SUPERFAMILY PROTEIN EXPRESSED IN
   BLOOD-VESSELS WITH A HEPARIN-BINDING CONSENSUS SEQUENCE
SO CANCER RESEARCH
LA English
DT Article
ID CELL-ADHESION MOLECULE; SACCHAROMYCES-CEREVISIAE; MONOCLONAL-ANTIBODIES;
   MESSENGER-RNAS; BETA-SUBUNIT; N-CAM; GENE; ACID; ANTIGEN; CLONING
AB A novel immunoglobulin-type protein expressed in blood vessels has been identified. The cDNA for AAMP (angio-associated, migratory cell protein) was first isolated from a human melanoma cell line during a search for motility-associated cell surface proteins. Upon analysis of the tissue distribution of AAMP, it was found to be expressed strongly in endothelial cells, cytotrophoblasts, and poorly differentiated colon adenocarcinoma cells found in lymphatics. The sequence of AAMP predicts a protein (M(r) 49,000) with distant identity (25%) to known proteins. It contains immunoglobulin-like domains [one with multiple homologies to deleted in colon carcinoma (DCC) protein], the WD40 repeat motif, and a heparin-binding consensus sequence. A 1.6-kilobase mRNA transcript of AAMP is detected in tissue culture cell lines and tissues. Affinity-purified polyclonal antibodies, anti-recombinant AAMP, and anti-peptide 189 (AAMP derived) recognize a M(r) 52,000 protein in human tissue and cellular extracts. The protein size is in keeping with the mRNA and predicted sequence. The AAMP-derived peptide, P189, contains a heparin-binding domain (dissociation constant, 14 pmol) and mediates heparin-sensitive cell adhesion. The shared expression of AAMP in endothelial cells, trophoblasts, and tumor cells implies a common function in migrating cells.
RP BECKNER, ME (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2A-33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 61
TC 24
Z9 25
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAY 15
PY 1995
VL 55
IS 10
BP 2140
EP 2149
PG 10
WC Oncology
SC Oncology
GA QX367
UT WOS:A1995QX36700027
PM 7743515
ER

PT J
AU LENFANT, C
AF LENFANT, C
TI THE APPROPRIATIONS HEARINGS - DELIVERING OUR MESSAGE
SO CIRCULATION
LA English
DT Editorial Material
RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 15
PY 1995
VL 91
IS 10
BP 2501
EP 2501
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QX587
UT WOS:A1995QX58700001
PM 7743606
ER

PT J
AU AGUIRRE, FV
   YOUNIS, LT
   CHAITMAN, BR
   ROSS, AM
   MCMAHON, RP
   KERN, MJ
   BERGER, PB
   SOPKO, G
   ROGERS, WJ
   SHAW, L
   KNATTERUD, G
   BRAUNWALD, E
AF AGUIRRE, FV
   YOUNIS, LT
   CHAITMAN, BR
   ROSS, AM
   MCMAHON, RP
   KERN, MJ
   BERGER, PB
   SOPKO, G
   ROGERS, WJ
   SHAW, L
   KNATTERUD, G
   BRAUNWALD, E
TI EARLY AND 1-YEAR CLINICAL OUTCOME OF PATIENTS EVOLVING NON-Q-WAVE VERSUS
   Q-WAVE MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS - RESULTS FROM THE
   TIMI-II STUDY
SO CIRCULATION
LA English
DT Article
DE MYOCARDIAL INFARCTION; THROMBOLYSIS; NON-QW INFARCTS; CLINICAL TRIALS
ID NATURAL-HISTORY; ANGIOGRAPHY; PREDICTORS; SURVIVORS; EVOLUTION; THERAPY;
   DEATH; TERM
AB Background There are few data comparing clinical outcome and potential indications for routine post-myocardial infarction cardiac catheterization and revascularization of patients who sustain a non-Q-wave versus Q-wave infarct after thrombolytic therapy.
   Methods and Results A secondary analysis of 2634 patients enrolled in the TIMI II trial with a first myocardial infarction was performed to determine 6-week and 1-year cardiac event rates and identify clinical and angiographic differences between the 1867 patients (70.9%) who evolved a Q-wave infarct and the 767 patients (29.1%) who sustained a non-Q-wave infarct after treatment with intravenous thrombolytic therapy. Male sex (85.3% versus 75.6%; P<.001) and anterior wall infarcts (53.8% versus 43.7%; P<.001) were more frequent in the Q-wave versus the non-Q-wave group. During recombinant tissue-type plasminogen activator (rTPA) infusion, a greater percentage of non-Q-wave patients (37.3% versus 23.5%; P=.001) had normalization of initial ST-segment elevation. Infarct-related artery patency (TIMI flow grade 2 or 3) (P=.02), complete infarct-related artery reperfusion (TIMI 3 flow grade) (P<.001), and the percentage of patients with a predischarge resting left ventricular ejection fraction >55% (P<.001) were greater in the non-Q-wave group. New congestive heart failure during hospitalization developed more frequently in Q-wave patients (18.9% versus 11.6%; P<.001). After 42 days, the occurrences of reinfarction (P=.76), death (P=.76), and combined death or reinfarction (P=.43) were similar in patients assigned to the invasive or conservative postlytic management strategy, regardless of infarct type. One-year mortality was 3.4% versus 4.4% for non-Q-wave versus Q-wave infarct type, respectively (P=.25).
   Conclusions Angiographic and clinical differences were observed between patients who present with initial ST-segment elevation and evolve early non-Q-wave versus Q-wave myocardial infarcts after treatment with rTPA, heparin, and aspirin. Early mortality and adverse clinical cardiac events in these patients are not significantly different after a conservative compared with an invasive treatment strategy, regardless of whether the infarct type is non-Q wave or Q wave.
C1 ST LOUIS UNIV,HLTH SCI CTR,ST LOUIS,MO 63103.
   MAYO CLIN,ROCHESTER,MN.
   UNIV ALABAMA,BIRMINGHAM,AL.
   GEORGE WASHINGTON UNIV,WASHINGTON,DC.
   NHLBI,BETHESDA,MD 20892.
   DUKE UNIV,DURHAM,NC.
   HARVARD UNIV,SCH MED,BOSTON,MA.
RP AGUIRRE, FV (reprint author), MARYLAND MED RES INST INC,TIMI COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA.
RI McMahon, Robert/C-5462-2009
NR 30
TC 74
Z9 74
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 MAY 15
PY 1995
VL 91
IS 10
BP 2541
EP 2548
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QX587
UT WOS:A1995QX58700010
PM 7743615
ER

PT J
AU CURB, JD
   RODRIGUEZ, BL
   BURCHFIEL, CM
   ABBOTT, RD
   CHIU, D
   YANO, K
AF CURB, JD
   RODRIGUEZ, BL
   BURCHFIEL, CM
   ABBOTT, RD
   CHIU, D
   YANO, K
TI SUDDEN-DEATH, IMPAIRED GLUCOSE-TOLERANCE, AND DIABETES IN
   JAPANESE-AMERICAN MEN
SO CIRCULATION
LA English
DT Article
DE DEATH, SUDDEN; GLUCOSE; DIABETES MELLITUS
ID CORONARY HEART-DISEASE; CARDIAC DEATH; MELLITUS; RISK
AB Background Diabetes and glucose intolerance have been shown to increase the risk of cardiovascular mortality in a number of different populations. Most studies have been based on short follow-up periods, and few have had sufficient numbers to allow researchers to look at sudden death as an outcome.
   Methods and Results The relation of sudden death, defined as unexpected death occurring within either 1 or 24 hours of first symptoms, to glucose intolerance measured by a nonfasting 1-hour postload measurement made in 1965 or history of diabetes was examined by use of 23 years of follow-up on the 8006 participants enrolled in the Honolulu Heart Program. After adjustment for baseline body mass index, hypertension, cholesterol, triglycerides, smoking, alcohol consumption, and left ventricular hypertrophy or strain, the relative risks for sudden death within 24 hours in individuals with high-normal (151 to 224 mg/dL), asymptomatic high glucose values (greater than or equal to 225 mg/dL), and diabetes compared with those with lower glucose values (<151 mg/dL) were 1.59, 2.22, and 2.76, respectively. All these relative risks were statistically significant (P less than or equal to.05). Trends for sudden death in 1 hour were similar. Among men with sudden death <1 hour after onset of symptoms, the strength of the association between diabetes and sudden death was stronger among those classified as having died of unknown causes who thus were more likely to have died of an arrhythmia than among those classified as having died of coronary heart disease.
   Conclusions The relations seen in these analyses indicate that individuals with glucose intolerance or diagnosed diabetes are at increased risk for sudden death.
C1 UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,DIV CLIN EPIDEMIOL,MANOA,HI.
   UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,DIV GERIATR MED,HONOLULU,HI 96817.
   UNIV HAWAII MANOA,DEPT FAMILY PRACTICE & COMMUNITY HLTH,HONOLULU,HI 96817.
   NHLBI,HONOLULU,HI.
   KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI.
   UNIV VIRGINIA,SCH MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908.
FU NHLBI NIH HHS [N01-HC-05102]
NR 20
TC 103
Z9 105
U1 1
U2 2
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 15
PY 1995
VL 91
IS 10
BP 2591
EP 2595
PG 5
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QX587
UT WOS:A1995QX58700016
PM 7743621
ER

PT J
AU VANPUTTEN, JPM
   PAUL, SM
AF VANPUTTEN, JPM
   PAUL, SM
TI BINDING OF SYNDECAN-LIKE CELL-SURFACE PROTEOGLYCAN RECEPTORS IS REQUIRED
   FOR NEISSERIA-GONORRHOEAE ENTRY INTO HUMAN MUCOSAL CELLS
SO EMBO JOURNAL
LA English
DT Article
DE HEPARAN SULFATE; MICROBIAL INVASION; NEISSERIA GONORRHOEAE; OPACITY
   PROTEIN; SYNDECAN
ID MAMMARY EPITHELIAL-CELLS; HEPARAN-SULFATE PROTEOGLYCANS;
   MAMMALIAN-CELLS; GROWTH-FACTOR; BORDETELLA-PERTUSSIS;
   HELICOBACTER-PYLORI; CHONDROITIN SULFATE; EUKARYOTIC CELLS; BACTERIAL
   ENTRY; PHASE VARIATION
AB Bacterial invasion of human mucosal cells is considered to be a primary event in the pathogenesis of a gonococcal infection, Here we report that cell surface heparan sulfate proteoglycans may play a role in the establishment of an infection, by functioning as receptors for the invasion-promoting gonococcal opacity protein adhesin, Chemical modification and enzymatic removal of proteoglycan receptors from cultured epithelial cells abolished opacity protein-associated gonococcal invasion, and mutant cell lines defective in proteoglycan synthesis were poor substrates for gonococcal attachment. The addition of purified receptor and receptor analogues totally blocked gonococcal entry into the cells, Heparin-affinity chromatography and receptor binding assays using recombinant bacteria producing defined opacity proteins and reconstituted receptor or purified receptor fragments as probes, identified one particular member of the opacity protein family (MS11-Opa(30)) as the primary ligand for this novel class of receptors for bacteria, Heparan sulfate proteoglycans with gonococcal binding activity were purified from various cell types derived from target tissues of gonococcal infection, including ME-180 endocervical cells and primary cultures of human corneal epithelium. The physico-chemical properties of the receptor indicate that it may belong to the syndecan proteoglycan family.
C1 MAX PLANCK INST BIOL,INFEKT BIOL ABT,D-72076 TUBINGEN,GERMANY.
RP VANPUTTEN, JPM (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA.
OI van Putten, Jos/0000-0002-4126-8172
NR 74
TC 182
Z9 183
U1 0
U2 6
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 MAY 15
PY 1995
VL 14
IS 10
BP 2144
EP 2154
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ862
UT WOS:A1995QZ86200002
PM 7774572
ER

PT J
AU SEPERACK, PK
   MERCER, JA
   STROBEL, MC
   COPELAND, NG
   JENKINS, NA
AF SEPERACK, PK
   MERCER, JA
   STROBEL, MC
   COPELAND, NG
   JENKINS, NA
TI RETROVIRAL SEQUENCES LOCATED WITHIN AN INTRON OF THE DILUTE GENE ALTER
   DILUTE EXPRESSION IN A TISSUE-SPECIFIC MANNER
SO EMBO JOURNAL
LA English
DT Article
DE DILUTE; MYOSIN HEAVY CHAIN; RETROVIRAL INSERTIONAL MUTAGENESIS; SOLO
   LTRS; TISSUE-SPECIFIC SPLICING
ID COAT-COLOR MUTATION; BRAIN MYOSIN-V; UNCONVENTIONAL MYOSIN; VIRUS-DNA;
   MOUSE; LOCUS; MICE; INSERTION; TRANSCRIPTION; ALLELES
AB The murine dilute coat color locus encodes an unconventional myosin heavy chain that is thought to be required for the elaboration or maintenance of dendrites or organelle transport in melanocytes and neurons. In previous studies we showed that the d mutation carried by many inbred strains of mice (now referred to as dilute viral, d(v)), is caused by the integration of an ecotropic murine leukemia virus (Emv-3) into the dilute gene and that phenotypic revertants of d(v) (termed d(+)) result from viral excision; a solo viral long terminal repeat (LTR) is all that remains in revertant DNA. In the studies described here we show that Emv-3 sequences are located within an intron of the dilute gene in a region of the C-terminal tail that is differentially spliced. We also show that these Emv-3 sequences result in the production of shortened and abnormally spliced dilute transcripts and that the level of this effect varies among tissues. This tissue-specific effect on dilute expression likely accounts for the absence of neurological abnormalities observed in d(v) mice. Surprisingly, we also found that the solo viral LTR present in revertant d(+) DNA produces a tissue-specific effect on dilute expression, although this effect is less dramatic than with the full-length provirus and produces no obvious mutant phenotype, These findings have important implications for understanding the effects of viral sequences on mammalian gene expression.
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702.
   UNIV TEXAS,SW MED CTR,DEPT PHYSIOL,DALLAS,TX 75235.
   INST ARTHRIT & AUTOIMMUN,W HAVEN,CT 06516.
FU NINDS NIH HHS [R01 NS30848]
NR 35
TC 104
Z9 105
U1 0
U2 2
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0261-4189
J9 EMBO J
JI Embo J.
PD MAY 15
PY 1995
VL 14
IS 10
BP 2326
EP 2332
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QZ862
UT WOS:A1995QZ86200021
PM 7774591
ER

PT J
AU HENKART, PA
AF HENKART, PA
TI APOPTOSIS - O DEATH, WHERE IS THY STING
SO JOURNAL OF IMMUNOLOGY
LA English
DT Note
ID PROGRAMMED CELL-DEATH; AURINTRICARBOXYLIC ACID; POLY(ADP-RIBOSE)
   POLYMERASE; CAENORHABDITIS-ELEGANS; SYMPATHETIC NEURONS; DNA
   FRAGMENTATION; CYTO-TOXICITY; GENE CED-3; PC12 CELLS; ENDONUCLEASE
RP HENKART, PA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA.
NR 52
TC 24
Z9 25
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 15
PY 1995
VL 154
IS 10
BP 4905
EP 4908
PG 4
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100001
PM 7730603
ER

PT J
AU FRANCIS, ML
   OKAZAKI, I
   MOSS, J
   KUROSKY, A
   PECANHA, LMT
   MOND, JJ
AF FRANCIS, ML
   OKAZAKI, I
   MOSS, J
   KUROSKY, A
   PECANHA, LMT
   MOND, JJ
TI CAMP-INDEPENDENT EFFECTS OF CHOLERA-TOXIN ON B-CELL ACTIVATION .3.
   CHOLERA-TOXIN A SUBUNIT-MEDIATED ADP-RIBOSYLATION ACTS SYNERGISTICALLY
   WITH IONOMYCIN OR IL-4 TO INDUCE B-CELL PROLIFERATION
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; GTP-BINDING PROTEIN; CYCLIC-AMP; TYROSINE
   PHOSPHORYLATION; LYMPHOCYTES-B; SURFACE-IMMUNOGLOBULIN;
   MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; ADENYLATE CYCLASE;
   PHOSPHOLIPASE-C
AB To investigate whether ADP-ribosylation of proteins by cholera toxin could influence B cell activation, B cells were incubated with the A subunit of cholera toxin. Ionomycin acted synergistically to induce B cell proliferation with the A subunit of cholera toxin but not with cAMP-enhancing agents or with the B subunit of cholera toxin, suggesting that the synergistic effect of the A subunit was mediated via ADP-ribosylation and not via cAMP elevations or ganglioside G(M1)f binding. Indeed, inhibitors of ADP-ribosylation blocked the synergistic effect. Unlike anti-Ig, B cell proliferation stimulated by LPS or by the combination of the A subunit and ionomycin was observed in protein kinase C (PKC)-depleted B cells. However, neither the A subunit nor ionomycin enhanced B cell proliferation stimulated by low dose LPS, suggesting that the A subunit plus ionomycin stimulated an activation pathway distinct from the LPS-stimulated pathway. Additionally, unlike LPS, the A subunit plus ionomycin did not stimulate B cells in vitro to secrete Ig. IL-4 acted synergistically with the A subunit to induce B cell proliferation to the same extent as it did with anti-Ig; unlike the anti-Ig plus IL-4 synergy, however, the A subunit plus IL-4-mediated synergy persisted in PKC-depleted B cells. Taken together, our data suggest that cholera toxin A subunit-catalyzed ADP-ribosylation modifies a non-Gs protein involved in the activation of B cells, either through a novel pathway or at a point distal to the activation of PKC along the anti-Ig-stimulated pathway.
C1 NHLBI,PULM & CRIT CARE MED BRANCH,BETHESDA,MD 20892.
   UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814.
   UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77550.
RP FRANCIS, ML (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,RHEUMATOL SECT,MED CTR BLVD,WINSTON SALEM,NC 27157, USA.
FU NIAID NIH HHS [R01-AI24273, R01 AI27465]; NINDS NIH HHS [R01 NS29261]
NR 53
TC 14
Z9 14
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 15
PY 1995
VL 154
IS 10
BP 4956
EP 4964
PG 9
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100007
PM 7730606
ER

PT J
AU GIESE, T
   DAVIDSON, WF
AF GIESE, T
   DAVIDSON, WF
TI IN CD8(+) T-CELL-DEFICIENT LPR/LPR MICE, CD4(+)B220(+) AND CD4(+)B220(-)
   T-CELLS REPLACE B220(+) DOUBLE-NEGATIVE T-CELLS AS THE PREDOMINANT
   POPULATIONS IN ENLARGED LYMPH-NODES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MRL/MP-LPR/LPR MICE; LUPUS-PRONE MICE; LPR-LPR MICE;
   MONOCLONAL-ANTIBODY; RECEPTOR REPERTOIRE; AUTOIMMUNE-DISEASE; DENDRITIC
   CELLS; CYCLE ANALYSIS; FAS ANTIGEN; THYMOCYTES
AB Mice homozygous for lpr or gld develop autoimmunity and progressive lymphoproliferative disease characterized by the accumulation of two unusual populations of B220(+) TCR-alpha beta(+) T cells, a predominant CD4(-)CD8(-) double-negative (DN) subset and a minor CD4(dull+) subset. B220(+) DN T cells appear to be derived from negatively selected thymocytes, but their immediate precursors have not been identified conclusively, and their relationship to CD4(+)B220(+) T cells is unclear. Our previous studies of lpr and gld mice treated chronically with anti-CD8 mAb provided evidence that the majority of B220(+) DN T cells are unrelated to CD4(+)B220(+) T cells and may be descended from peripheral thymus-derived CD8(+) T cells. To investigate the contributions of MHC class I-selected thymus-derived T cells to the production of B220(+) DN T cells and to the accumulation of CD4(+) T cell subsets, we studied C3H-lpr and -gld mice rendered deficient in CD8(+) T cells by the introduction of disrupted beta(2)-microglobulin (beta(2)-m) genes. These CD8(+) T cell-deficient mice developed massively enlarged lymph nodes, in which CD4(+)B220(+) T cells and CD4(+) T cells replaced B220(+) DN T cells as the dominant T cell subsets. As a population, the CD4(+)B220(+) T cells were depleted of autoreactive populations specific for endogenous retroviral superantigens and were enriched for V beta 8.3(+) T cells. The deficiency of CD8(+) T cells in beta(2)-m(-/-)-lpr mice had no effects on the accumulation of primed CD4(+) T cells or autoreactive B cells. The selective reduction in B220(+) DN T cells and corresponding accumulation of CD4(+)B220(+) T cells in beta(2)-m(-/-)-lpr mice provide strong evidence that 1) the majority of B220(+) DN T cells are unrelated to CD4(+) T cells and their development and/or accumulation is dependent on MHC class I expression; and 2) CD4(+)B220(+) T cells are a remarkably similar, but separate, lineage of cells that develop independently of thymus-derived CD8(+) T cells and class I MHC expression.
C1 NCI,GENET LAB,BETHESDA,MD 20892.
NR 59
TC 47
Z9 47
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 15
PY 1995
VL 154
IS 10
BP 4986
EP 4995
PG 10
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100010
PM 7537297
ER

PT J
AU BRONTE, V
   TSUNG, K
   RAO, JB
   CHEN, PW
   WANG, M
   ROSENBERG, SA
   RESTIFO, NP
AF BRONTE, V
   TSUNG, K
   RAO, JB
   CHEN, PW
   WANG, M
   ROSENBERG, SA
   RESTIFO, NP
TI IL-2 ENHANCES THE FUNCTION OF RECOMBINANT POXVIRUS-BASED VACCINES IN THE
   TREATMENT OF ESTABLISHED PULMONARY METASTASES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; TUMOR-CELLS; FOWLPOX VIRUS; HUMAN
   INTERLEUKIN-2; EXPRESSION VECTOR; MAMMALIAN-CELLS; IMMUNE-RESPONSE;
   CLASS-I; GENE; ANTIGEN
AB Neoplastic cells are generally poor immunogens. Transfection of the murine tumor CT-26 with beta-galactosidase (beta-gal), a protein from Escherichia coli, did not alter its growth rate in vivo, or its lethality, and did not elicit a measurable anti-beta-gal immune response. Immunization with beta-gal-expressing recombinant vaccinia viruses (rVV) elicited specific anti-beta-gal cytolytic T lymphocytes, but rVV-beta-gal was only marginally therapeutic when given to tumor-bearing mice. With the aim of expanding the immune response against beta-gal, used here as a model tumor Ag, we gave mice exogenous IL-2 starting 12 h after the poxvirus. The therapeutic effectiveness of the combination of poxvirus and IL-2 was far greater than either of these treatments alone. When the cDNA for IL-2 was inserted into the viral genome of the rVV construct to make a double recombinant (drVV), antitumor activity was further augmented. One mechanism of action may be the enhanced activation or expansion of cytotoxic T cells, because a marked increase in primary cytotoxic responses against vaccinia determinants was observed. interestingly, other cytokines (mGM-CSF, mTNF-alpha, and mIFN-gamma) inserted into the rVV genome did not modify the efficacy of the rVV constructs. The increase in specific CTL responses against beta-gal by drVV expressing the tumor-associated Ags (TAA) and IL-2 was more pronounced in mice bearing the lacZ-transduced tumor than in those bearing the parental cell line, suggesting that the TAA presented by growing tumor cells can either pre-activate or otherwise amplify the immune response induced by the rVV. Unfortunately, in several long-term surviving mice, tumor recurred that no longer expressed beta-gal. These results indicate that treatment of disseminated tumors by using recombinant viruses expressing TAA can be enhanced by IL-2 provided exogenously, or encoded within the recombinant virus.
C1 NCI,SURG BRANCH,BETHESDA,MD 20892.
   WASHINGTON UNIV,BIOL THERAPY LAB,ST LOUIS,MO 63110.
   NIH,HLTH RES SCHOLAR PROGRAM,HOWARD HUGHES MED INST,BETHESDA,MD 20814.
RI Restifo, Nicholas/A-5713-2008; 
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]
NR 52
TC 99
Z9 99
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 15
PY 1995
VL 154
IS 10
BP 5282
EP 5292
PG 11
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100041
PM 7730632
ER

PT J
AU HIRASAWA, N
   SANTINI, F
   BEAVEN, MA
AF HIRASAWA, N
   SANTINI, F
   BEAVEN, MA
TI ACTIVATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CYTOSOLIC
   PHOSPHOLIPASE A(2) PATHWAY IN A RAT MAST-CELL LINE - INDICATIONS OF
   DIFFERENT PATHWAYS FOR RELEASE OF ARACHIDONIC-ACID AND SECRETORY
   GRANULES
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID BASOPHILIC LEUKEMIA-CELLS; RBL-2H3 CELLS; TYROSINE PHOSPHORYLATION;
   SIGNAL-TRANSDUCTION; MAP KINASE; STIMULATION; ANTIGEN; EXOCYTOSIS;
   INHIBITORS; RECEPTORS
AB The role of mitogen-activated protein (MAP) kinase in the release of arachidonic acid was examined in a mutated mast cell (RBL-2H3(ml)) line that expressed both native Fc epsilon R1 and the G protein-coupled muscarinic mi receptor. Stimulation of these cells with Ag, carbachol, Ca2+-ionophore, or thapsigargin resulted in the phosphorylation of Raf1, MEK1, p42(mapk) MAp kinase, and the recently cloned cytosolic phospholipase A(2) (PLA(2)) and increased activities of both MAP kinase and PLA(2), as well as release of arachidonic acid. Because this cascade of reactions was inhibited by guanosine 5'-(2-thiodiphosphate), it appeared to be dependent on a GTP-binding protein(s). These reactions, however, were not dependent on protein kinase C; the cascade was totally resistant to the actions of a selective protein kinase C inhibitor, Ro31-7549, whereas release of the secretory granule marker, hexosaminidase, was blocked by this agent. Differences between the stimulatory pathways for release of arachidonic acid and hexosaminidase were evident also from the effects of the kinase inhibitor, quercetin. The above cascade of reactions, including release of arachidonic acid, was inhibited by 50% with similar to 5 ELM quercetin, whereas secretion was inhibited only at higher concentrations of inhibitor. Moreover, inhibition of the activation of MAP kinase and release of arachidonic acid were closely correlated. This and previous findings suggested that release of arachidonic acid was attributable to the regulation of cytosolic PLA(2) by MAP kinase (for activation of PLA(2)) and Ca2+ for association of PLA(2) with the membrane), whereas release of hexosaminidase was regulated primarily by Ca2+ and protein kinase C.
C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892.
NR 58
TC 164
Z9 165
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 15
PY 1995
VL 154
IS 10
BP 5391
EP 5402
PG 12
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100053
PM 7730640
ER

PT J
AU MATSUKAWA, A
   YOSHIMURA, T
   MAEDA, T
   OHKAWARA, S
   TAKAGI, K
   YOSHINAGA, M
AF MATSUKAWA, A
   YOSHIMURA, T
   MAEDA, T
   OHKAWARA, S
   TAKAGI, K
   YOSHINAGA, M
TI NEUTROPHIL ACCUMULATION AND ACTIVATION BY HOMOLOGOUS IL-8 IN RABBITS -
   IL-8 INDUCES DESTRUCTION OF CARTILAGE AND PRODUCTION OF IL-1 AND IL-1
   RECEPTOR ANTAGONIST IN-VIVO
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; CHEMOTACTIC FACTOR; POLYMORPHONUCLEAR LEUKOCYTES;
   MOLECULAR-CLONING; PROTEIN-1 NAP-1; CDNA CLONING; IN-VIVO;
   INTERLEUKIN-8; EXPRESSION; CELLS
AB Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10 mu g of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1 beta and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1 beta and IL-1Ra positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1 beta and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1 beta and IL-1 Ra.
C1 KUMAMOTO UNIV,SCH MED,DEPT ORTHOPED,KUMAMOTO 860,JAPAN.
   NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702.
RP MATSUKAWA, A (reprint author), KUMAMOTO UNIV,SCH MED,DEPT PATHOL,2-2-1 HONJO,KUMAMOTO 860,JAPAN.
NR 50
TC 71
Z9 76
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 15
PY 1995
VL 154
IS 10
BP 5418
EP 5425
PG 8
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100056
PM 7730643
ER

PT J
AU MUROCACHO, CA
   PANTALEO, G
   FAUCI, AS
AF MUROCACHO, CA
   PANTALEO, G
   FAUCI, AS
TI ANALYSIS OF APOPTOSIS IN LYMPH-NODES OF HIV-INFECTED PERSONS - INTENSITY
   OF APOPTOSIS CORRELATES WITH THE GENERAL STATE OF ACTIVATION OF THE
   LYMPHOID-TISSUE AND NOT WITH STAGE OF DISEASE OR VIRAL BURDEN
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROGRAMMED CELL-DEATH; HUMAN-IMMUNODEFICIENCY-VIRUS; MATURE T-CELLS;
   LYMPHOCYTES-T; AIDS PATHOGENESIS; IMMUNE-SYSTEM; EXPRESSION; MECHANISM;
   RECEPTOR; ANTIGEN
AB The occurrence of in vivo apoptosis was investigated in lymph node sections obtained from HIV-infected persons at different stages of disease. The degree of apoptosis in lymph nodes from HIV-infected individuals was compared with that observed in lymph nodes obtained from HIV-negative individuals. Apoptosis was readily detected in lymph nodes obtained from both HIV-negative and HIV-positive persons; however, the degree of apoptosis in lymph nodes obtained from HIV-positive persons was three to four times higher than that observed in the lymph nodes obtained from HIV-negative persons. In contrast to HIV-negative lymph nodes in which apoptosis was confined largely to germinal centers, in HIV-positive lymph nodes all functional compartments of the lymph node (i.e., cortex, paracortex, and sinuses) were extensively involved by this phenomenon. Furthermore, a significant correlation was observed between intensity of apoptosis and degree of activation of the lymphoid tissue associated with HIV infection. In contrast, intensity of apoptosis correlated neither with the clinical stage of HIV disease nor with the viral burden in the lymph node. Finally, apoptosis was not restricted only to CD4(+) T cells; both B cells and CD8(+) T cells were found to undergo apoptosis. Taken together, these results indicate that the increased intensity of the apoptotic phenomenon in HIV infection is caused by the general state of immune activation, and is independent of the progression of HIV disease and of the levels of viral load.
C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892.
RI Pantaleo, Giuseppe/K-6163-2016
NR 72
TC 299
Z9 305
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 15
PY 1995
VL 154
IS 10
BP 5555
EP 5566
PG 12
WC Immunology
SC Immunology
GA QW901
UT WOS:A1995QW90100070
PM 7730654
ER

PT J
AU OWENS, IS
AF OWENS, IS
TI THE LEADERS OF SCIENCE - THE READERS OF THE SCIENTIST
SO SCIENTIST
LA English
DT Editorial Material
RP OWENS, IS (reprint author), NICHHD,HUMAN GENET BRANCH,GENET DISORDERS DRUG METAB SECT,BETHESDA,MD 20892, USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SCIENTIST INC
PI PHILADELPHIA
PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104
SN 0890-3670
J9 SCIENTIST
JI Scientist
PD MAY 15
PY 1995
VL 9
IS 10
BP 8
EP 8
PG 1
WC Information Science & Library Science; Multidisciplinary Sciences
SC Information Science & Library Science; Science & Technology - Other
   Topics
GA QY335
UT WOS:A1995QY33500007
ER

PT J
AU WLODAWER, A
AF WLODAWER, A
TI PROTEASOME - A COMPLEX PROTEASE WITH A NEW FOLD AND A DISTINCT MECHANISM
SO STRUCTURE
LA English
DT Review
ID THERMOPLASMA-ACIDOPHILUM
AB The structure of the proteasome from Thermoplasma acidophilum introduces threonine proteases as a fifth class of proteolytic enzymes, and offers insights into the catalytic activity of this complicated piece of molecular machinery with its 14 active sites.
RP WLODAWER, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702, USA.
FU NCI NIH HHS [N01-CO-46000]
NR 15
TC 12
Z9 12
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 MAY 15
PY 1995
VL 3
IS 5
BP 417
EP 420
DI 10.1016/S0969-2126(01)00172-1
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA RA483
UT WOS:A1995RA48300001
PM 7663937
ER

PT J
AU PALIOGIANNI, F
   BOUMPAS, DT
AF PALIOGIANNI, F
   BOUMPAS, DT
TI GLUCOCORTICOIDS REGULATE CALCINEURIN-DEPENDENT TRANSACTIVATING PATHWAYS
   FOR INTERLEUKIN-2 GENE-TRANSCRIPTION IN HUMAN T-LYMPHOCYTES
SO TRANSPLANTATION
LA English
DT Article
ID 3' UNTRANSLATED REGION; NUCLEAR FACTOR; CYCLOSPORINE-A; MESSENGER-RNA;
   DNA-BINDING; C-JUN; NF-AT; RECEPTOR; CELLS; EXPRESSION
AB Glucocorticoids (GC) inhibit IL-2 gene transcription by interfering with the binding of the nuclear factor activator protein-1 on the IL-2 promoter. Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is an essential component of the T cell antigen receptor signal transduction pathway leading to IL-2 gene transcription. Therefore, we have asked whether this phosphatase may also be regulated by GC. Jurkat T cells were cotransfected with plasmids containing the intact IL-2 promoter or its NF-AT and Oct-1 motifs, and a deletion mutant (Delta CaM-AI) of calcineurin known to have Ca2+-independent constitutive phosphatase activity. Cotransfection of IL-2 promoter with Delta CaM-AI allowed the activation of IL-2 promoter in the presence of phorbol ester alone. Under these conditions dexamethasone (Dex; 10(-6) M) inhibited IL-2 promoter activation by 50-60%. The inhibitory effect of Dex was specific, as demonstrated by experiments using an unrelated promoter (simian virus 40) and estradiol. Furthermore, it was completely reversed in the presence of excess amounts of the glucocorticoid antagonist RU 486, which suggests that it is mediated through the glucocorticoid receptor, Overexpression of calcineurin via Delta CaM-AI in Jurkat cells decreased their apparent sensitivity to Dex (similar to 5-fold increase in IC50). Similar results were obtained with the NF-AT and Oct-1 constructs, which are also known to be activated by calcineurin. Thus, in addition to their known inhibitory effects on activator protein-1, GC also inhibit calcineurin-dependent pathways for T cell activation.
RP PALIOGIANNI, F (reprint author), NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BLDG 10,ROOM 3N112,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 35
TC 29
Z9 29
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAY 15
PY 1995
VL 59
IS 9
BP 1333
EP 1339
DI 10.1097/00007890-199505000-00019
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA QY984
UT WOS:A1995QY98400019
PM 7762070
ER

PT J
AU FINCH, PW
   LENGEL, C
   CHEDID, M
AF FINCH, PW
   LENGEL, C
   CHEDID, M
TI CLONING AND CHARACTERIZATION OF THE PROMOTER REGION OF THE HUMAN
   KERATINOCYTE GROWTH-FACTOR GENE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID REGULATORY REGIONS; FACTOR RECEPTORS; OVALBUMIN GENE; EXPRESSION;
   SEQUENCE; IDENTIFICATION; TRANSCRIPTION; PROTEIN; FAMILY; INTERLEUKIN-6
AB Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family of related proteins, is expressed by stromal fibroblasts and acts on epithelial cells in a paracrine fashion. To understand the mechanisms responsible for regulating normal KGF expression and how these might be altered in disease, the 5'-flanking region of this gene was cloned. The presence of two KGF transcription initiation sites was suggested by ribonuclease protection assay and confirmed by primer extension analysis. Examination of the genomic DNA sequence revealed the presence of the putative promoter sequences TATTTA and CCAAT, located 31 and 50 base pairs upstream, respectively, from the first of the two mRNA start points, and putative initiator sequences surrounding each transcription start site, Transient transfection into murine NIH/3T3 fibroblasts demonstrated that the region required for basal level KGF promoter activity was located between bases -225 and +190. Inclusion of sequences between -1503 and -775 markedly reduced promoter activation, indicating the presence of negative regulatory element(s) in this region. A similar pattern of promoter activation was detected in human fibroblasts and in murine C2C12 myoblasts. In contrast, no chloramphenicol acetyltransferase activity was observed in macrophages and epithelial and lymphoid cells transfected with the same constructs. Northern blot analysis revealed a strong correlation between KGF RNA expression and promoter activation in all cells tested. Activation of the KGF promoter could be induced by the proinflammatory cytokines interleukin 1 and interleukin 6 and by the adenylate cyclase activator forskolin. Taken together, these results indicate the existence of cis-acting element(s) responsible for selective activation of the KGF promoter only in cells that express KGF mRNA and may provide a mechanistic basis for KGF gene expression during inflammation.
C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892.
   BROWN UNIV,RHODE ISL HOSP,DEPT CLIN NEUROSCI,PROVIDENCE,RI 02903.
NR 50
TC 37
Z9 39
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 MAY 12
PY 1995
VL 270
IS 19
BP 11230
EP 11237
DI 10.1074/jbc.270.19.11230
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX865
UT WOS:A1995QX86500033
PM 7744756
ER

PT J
AU GIULIANI, C
   SAJI, M
   NAPOLITANO, G
   PALMER, LA
   TANIGUCHI, SI
   SHONG, M
   SINGER, DS
   KOHN, LD
AF GIULIANI, C
   SAJI, M
   NAPOLITANO, G
   PALMER, LA
   TANIGUCHI, SI
   SHONG, M
   SINGER, DS
   KOHN, LD
TI HORMONAL MODULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I
   GENE-EXPRESSION INVOLVES AN ENHANCER A-BINDING COMPLEX CONSISTING OF
   FRA-2 AND THE P50 SUBUNIT OF NF-KAPPA-B
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RAT THYROTROPIN RECEPTOR; AUTOIMMUNE THYROID-DISEASE; HLA-DR EXPRESSION;
   TRANSCRIPTION FACTORS; DNA-BINDING; C-JUN; GLUCOCORTICOID RECEPTOR;
   EPITHELIAL-CELLS; FRTL-5 CELLS; INTERFERON
AB Hydrocortisone decreases major histocompatibility complex (MHC) class I gene expression in rat thyroid cells and counteracts increases induced by interferons. Using FRTL-5 cells transfected with class I promoter-reporter gene chimeras, we show that hydrocortisone action is transcriptional and mediated by an element located between 180 and 170 base pairs upstream of the start of transcription. Gel shift assays reveal that hydrocortisone causes the decrease of a specific protein-DNA complex; this same complex, referred to as Mod-1, is increased by interferon. Oligonucleotide competition assays reveal that the Mod-1 complex is associated with enhancer A of the class I gene, -180 to -170 base pairs (5'-GGGGAGTCCCC-3'), immediately upstream of the interferon response element. Antibodies to fra-2, a fos family member, and to the p50, but not the p65, subunit of NF-kappa B supershift the Mod-1 complex. We suggest that hydrocortisone decreases MHC class I gene expression by reducing the formation of Mod-1, which contains both p50 and fra-2; interferon reverses the hydrocortisone effect and increases Mod-1 formation. These observations are relevant to the molecular basis of hydrocortisone therapy in autoimmune thyroid disease and to the actions of interferon to exacerbate or induce autoimmune disease.
C1 NIDDK,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892.
   NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892.
RI Saji, Motoyasu/E-4007-2011
NR 57
TC 38
Z9 38
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 MAY 12
PY 1995
VL 270
IS 19
BP 11453
EP 11462
DI 10.1074/jbc.270.19.11453
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX865
UT WOS:A1995QX86500062
PM 7744783
ER

PT J
AU HESSELGESSER, J
   CHITNIS, CE
   MILLER, LH
   YANSURA, DG
   SIMMONS, LC
   FAIRBROTHER, WJ
   KOTTS, C
   WIRTH, C
   GILLECECASTRO, BL
   HORUK, R
AF HESSELGESSER, J
   CHITNIS, CE
   MILLER, LH
   YANSURA, DG
   SIMMONS, LC
   FAIRBROTHER, WJ
   KOTTS, C
   WIRTH, C
   GILLECECASTRO, BL
   HORUK, R
TI A MUTANT OF MELANOMA GROWTH-STIMULATING ACTIVITY DOES NOT ACTIVATE
   NEUTROPHILS BUT BLOCKS ERYTHROCYTE INVASION BY MALARIA
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RECEPTOR-BINDING; INTERLEUKIN-8 RECEPTORS; 3-DIMENSIONAL STRUCTURE;
   SCANNING MUTAGENESIS; CHEMOKINE RECEPTOR; PLASMODIUM-VIVAX; CYTOKINE
   FAMILY; DETERMINANTS; RESOLUTION; PARASITE
AB Alanine scanning mutagenesis of the charged amino acids of melanoma growth stimulating activity (MGSA) was used to identify specific residues that are involved in binding to the human erythrocyte Duffy antigen/chemokine receptor (DARC) and to the type B interleukin-8 receptor (IL-8RB) on neutrophils, Receptor binding and biological studies with the alanine scan mutants of MGSA demonstrate that MGSA binds to DARC and the IL-8RB through distinct binding regions, One of the MGSA mutants, E6A, binds to human erythrocytes and is able to inhibit malaria invasion as efficiently as wild type MGSA but has a severely reduced ability to bind to or signal through the IL-8RB, Mutant chemokines like E6A could prove to be useful therapeutically for the design of receptor blocking drugs that inhibit erythrocyte invasion by Plasmodium vivax malaria.
C1 GENENTECH INC,S SAN FRANCISCO,CA 94080.
   NIH,MALARIA RES LAB,BETHESDA,MD 20205.
NR 29
TC 49
Z9 49
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 MAY 12
PY 1995
VL 270
IS 19
BP 11472
EP 11476
DI 10.1074/jbc.270.19.11472
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX865
UT WOS:A1995QX86500064
PM 7744785
ER

PT J
AU BURGESS, EM
   RUELL, JA
   ZALKOW, LH
   HAUGWITZ, RD
AF BURGESS, EM
   RUELL, JA
   ZALKOW, LH
   HAUGWITZ, RD
TI MOLECULAR SIMILARITY FROM ATOMIC ELECTROSTATIC MULTIPOLE COMPARISONS -
   APPLICATION TO ANTI-HIV DRUGS
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID SHAPE
AB A procedure is presented for the rapid calculation of the similarity between a pair of molecules based on atomic electrostatic multipole comparison. The multipoles are derived from semiempirical SCF wave functions, and the results obtained compare favorably with ab initio results. The method is illustrated by correlating the similarity and anti-HIV-1 activity of a series of azo compounds. Some generalizations are presented on the structure-activity relationships which are based on the atomic multipole distribution in the azo compounds.
C1 NCI,DRUG SYNTH & CHEM BRANCH,ROCKVILLE,MD 20852.
RP BURGESS, EM (reprint author), GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332, USA.
FU NCI NIH HHS [N01-CM-17550]
NR 30
TC 8
Z9 8
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 MAY 12
PY 1995
VL 38
IS 10
BP 1635
EP 1640
DI 10.1021/jm00010a007
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA QY144
UT WOS:A1995QY14400007
PM 7752188
ER

PT J
AU ZHANG, PW
   ZHANG, WJ
   LIU, RY
   HARRIS, B
   SKOLNICK, P
   COOK, JM
AF ZHANG, PW
   ZHANG, WJ
   LIU, RY
   HARRIS, B
   SKOLNICK, P
   COOK, JM
TI SYNTHESIS OF NOVEL IMIDAZOBENZODIAZEPINES AS PROBES OF THE PHARMACOPHORE
   FOR DIAZEPAM-INSENSITIVE GABA(A) RECEPTORS
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID BENZODIAZEPINE RECEPTORS; HIGH AFFINITIES; BINDING-SITES; LIGANDS;
   DIRECTIONALITY; EXPRESSION; ANTAGONIST; FEATURES; PROTEINS
AB The syntheses of a series of novel imidazobenzodiazepines and their affinities for diazepam sensitive (DS) and diazepam insensitive (DI) GABA(A) receptors are described. Imidazobenzodiazepines belong to one of the very few chemical families which exhibit high to moderate potency for DI GABA(A) receptors. Although imidazobenzodiazepines such as Ro 15-4513, 20, are the most potent DI GABA(A) receptor ligands described to date, their selectivity for DI versus DS GABA(A) receptors is only marginal. Previous structure-activity relationship (SAR) studies of imidazobenzodiazepines have indicated that the 3- and 8-positions are critical for high-affinity binding to DI GABA(A) receptors (J. Med. Chem. 1993, 36, 479-490. J. Med. Chem. 1993, 36, 1001-1006. J. Med. Chem. 1993, 36, 1820-1830). In order to determine why the ester function is critical to high affinity at the DI site, we have synthesized several derivatives which have substituents other than an ester at the C(3) position including 3-alkyl-, 3-alkylketo-, 3-alkyl ether, and 3-dialkylamino-substituted imidazobenzodiazepines. The SAR analysis of these compounds when combined with that of several pyrazoloquinolinones indicates that interactions at H1 and L1 as well as interactions at H2 anti to the imidazole N(2) and at a lipophilic pocket (labeled LDi) about the 3-position are required in order for imidazobenzodiazepines to exhibit selectivity and high affinity for DI GABA(A) receptors. Furthermore, the imidazobenzo diazepines substituted with an electron-donating group (alkoxy function) at position 8 revealed that the change of the substituent at C(8) from an electron-withdrawing to a donating function did not substantially alter either ligand affinity or selectivity for DI GABA(A) receptors. Thus; a pharmacophore is proposed for DI GABA(A) receptor ligands, which is characterized by the requirement of a lipophilic pocket LDi about the C(3) position of imidazobenzodiazepines. Using this model, two pyrazoloquinolinone derivatives were designed and synthesized. Their affinities and selectivities for DI GABA(A) receptors are consistent with those predicted by the DI GABA(A) receptor pharmacophore. In addition, examination of the in vitro binding data of 3-alkyl ether analogs confirms that the anti conformation of the ester group at the C(3) position of imidazobenzodiazepines (Ro15-4513, 20 series) is preferred at both DI and DS GABA(A) receptors. This constitutes the first evidence (other than molecular modeling) to support the auxiliary involvement of H2 at the DI site and is important with regard to the synthesis of other DI GABA(A) receptor selective ligands in the future. Comparison of the included volume developed here for the DI site vs the included volume for the DS site clearly demonstrates that the DI site is a smaller (subsite) binding cleft than the DS site and is clearly devoid of most of lipophilic area L3 (Figure 6b).
C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53201.
   NIDDK,NEUROSCI LAB,BETHESDA,MD 20892.
NR 35
TC 41
Z9 42
U1 0
U2 3
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 MAY 12
PY 1995
VL 38
IS 10
BP 1679
EP 1688
DI 10.1021/jm00010a013
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA QY144
UT WOS:A1995QY14400013
PM 7752192
ER

PT J
AU KIESEWETTER, DO
   SILVERTON, JV
   ECKELMAN, WC
AF KIESEWETTER, DO
   SILVERTON, JV
   ECKELMAN, WC
TI SYNTHESES AND BIOLOGICAL PROPERTIES OF CHIRAL FLUOROALKYL QUINUCLIDINYL
   BENZILATES
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; POSITRON EMISSION TOMOGRAPHY;
   POTENTIAL RADIOPHARMACEUTICALS; 3-QUINUCLIDINYL BENZILATE;
   COMPUTED-TOMOGRAPHY; BABOON BRAIN; INVIVO; BINDING; INVITRO; HEART
AB Previously, (R)-quinuclidinyl (R)-4-iodobenzilate ((R,R)-IQNB), a muscarinic receptor antagonist, has been labeled with I-123 and I-125 for use in in vitro and in vivo studies in animals and humans. We have prepared fluoroalkyl analogs of QNB, which are amenable to labeling with F-18, for potential imaging applications with positron emission tomography. The enantiomers of (fluoroalkyl)benzilic acids were prepared via an enantioselective Grignard addition reaction. Subsequent coupling of the enantiomeric (fluoroalkyl)benzilic acid with a selected enantiomer of quinuclidinol provides fluorinated analogs of QNB with known stereochemistry at each of the stereogenic centers. These compounds exhibit different affinities for the muscarinic receptor tissue subtypes in vitro. (R,R)-4-(Fluoromethyl)-QNB, (R,R)-IQNB, and (R,R)-4-(fluoroethyl)-QNB exhibit selectivity for the M1 subtype, and (R,S)-4-(fluoromethyl)-QNB exhibits selectivity for the M2 subtype.
C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892.
RP KIESEWETTER, DO (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT POSIT EMISS TOMOG,BLDG 10,RM 1C401,10 CTR DR,MSC 1180,BETHESDA,MD 20892, USA.
NR 41
TC 30
Z9 31
U1 0
U2 3
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 MAY 12
PY 1995
VL 38
IS 10
BP 1711
EP 1719
DI 10.1021/jm00010a016
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA QY144
UT WOS:A1995QY14400016
PM 7752195
ER

PT J
AU JACOBSON, KA
   SIDDIQI, SM
   OLAH, ME
   JI, XD
   MELMAN, N
   BELLAMKONDA, K
   MESHULAM, Y
   STILES, GL
   KIM, HO
AF JACOBSON, KA
   SIDDIQI, SM
   OLAH, ME
   JI, XD
   MELMAN, N
   BELLAMKONDA, K
   MESHULAM, Y
   STILES, GL
   KIM, HO
TI STRUCTURE-ACTIVITY-RELATIONSHIPS OF 9-ALKYLADENINE AND RIBOSE-MODIFIED
   ADENOSINE DERIVATIVES AT RAT A(3) ADENOSINE RECEPTORS
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MOLECULAR-CLONING; ANTAGONISTS; NUCLEOSIDE; EXPRESSION; ACTIVATION;
   AGONISTS; ANALOGS; CYCLASE; BRAIN
AB 9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.
C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710.
   DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710.
RP JACOBSON, KA (reprint author), NIDDK,MOLEC RECOGNIT SECT,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-17,BETHESDA,MD 20892, USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20]; NHLBI NIH HHS
   [R01HL35134]
NR 43
TC 61
Z9 62
U1 0
U2 3
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 MAY 12
PY 1995
VL 38
IS 10
BP 1720
EP 1735
DI 10.1021/jm00010a017
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA QY144
UT WOS:A1995QY14400017
PM 7752196
ER

PT J
AU CLERGET, M
   JIN, DJ
   WEISBERG, RA
AF CLERGET, M
   JIN, DJ
   WEISBERG, RA
TI A ZINC-BINDING REGION IN THE BETA' SUBUNIT OF RNA-POLYMERASE IS INVOLVED
   IN ANTITERMINATION OF EARLY TRANSCRIPTION OF PHAGE HK022
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE GENES; BACTERIAL; PHAGE LAMBDA; TRANSCRIPTION ELONGATION; TRANSCRIPTION
   TERMINATION
ID N-GENE-PRODUCT; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; TERMINATION
   EFFICIENCY; ELONGATION-FACTOR; NUN PROTEIN; MUTATIONS; REQUIREMENT;
   CLEAVAGE; IDENTIFICATION
AB Antitermination of early transcription in phage HK022 requires no virus-encoded proteins and thus differs from antitermination by other lambdoid phages. It does require cis-acting phage sequences, which may be analogous to the lambdoid nut sites. To identify host proteins involved in antitermination, we isolated 14 Escherichia coli mutants that are specifically blocked in HK022 growth. The mutations are located in the rpoC gene, which encodes the beta' subunit of RNA polymerase. Each mutation alters one of three amino acid residues located within a cluster of four completely conserved cysteine residues that are believed to bind zinc. We examined the effect of one mutation on HK022 antitermination in vivo. rpoCY75N greatly reduced readthrough of a strong rho-independent transcription terminator placed downstream of the HK022 P-L promoter and nutL analog, but did not decrease promoter activity Purified enzyme had a similar effect on P-L-directed transcription in vitro: wild-type but not mutant polymerase read through a strong rho-independent terminator located immediately downstream of the nutL analog with high efficiency We suggest that interaction of the putative zinc-binding domain of the RNA polymerase beta' subunit with the HK022 antitermination sites suppresses transcription termination, and that this interaction can occur in the absence of other proteins.
C1 NICHHD,GENET MOLEC LAB,MICROBIAL GENET SECT,BETHESDA,MD 20892.
   NCI,MOLEC BIOL LAB,BETHESDA,MD 20892.
NR 53
TC 32
Z9 32
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 MAY 12
PY 1995
VL 248
IS 4
BP 768
EP 780
DI 10.1006/jmbi.1995.0259
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX872
UT WOS:A1995QX87200006
PM 7752239
ER

PT J
AU BENDELAC, A
   LANTZ, O
   QUIMBY, ME
   YEWDELL, JW
   BENNINK, JR
   BRUTKIEWICZ, RR
AF BENDELAC, A
   LANTZ, O
   QUIMBY, ME
   YEWDELL, JW
   BENNINK, JR
   BRUTKIEWICZ, RR
TI CD1 RECOGNITION BY MOUSE NK1(+) T-LYMPHOCYTES
SO SCIENCE
LA English
DT Article
ID ALPHA-BETA+ THYMOCYTES; LYMPHOKINE SECRETION; ANTIGEN; EXPRESSION;
   CELLS; THYMUS; CD4+; EPITHELIUM; SELECTION; MOLECULES
AB Rare major histocompatibility complex (MHC) class I-like CD1-specific T cells have been isolated from human blood, but it has not been determined whether these clones are part of a defined subset of CD1-specific T cells selected during T cell development, or whether their recognition of CD1 is a fortuitous cross-reaction. In mice, an entire subset of alpha beta thymocytes with a unique phenotype was found to be CD1-specific. This particular subset, and its human counterpart, provide evidence that CD1 has a general role in selecting and interacting with specialized alpha beta T cells.
C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892.
   PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544.
   NIAID,VIRAL DIS LAB,BETHESDA,MD 20892.
RP BENDELAC, A (reprint author), PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544, USA.
RI yewdell, jyewdell@nih.gov/A-1702-2012; Lantz, Olivier/J-4960-2012
OI Lantz, Olivier/0000-0003-3161-7719
NR 42
TC 733
Z9 745
U1 2
U2 4
PU AMER ASSOC ADVAN SCIENCE
PI WASHINGTON
PA 1333 H ST NW, WASHINGTON, DC 20005
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 12
PY 1995
VL 268
IS 5212
BP 863
EP 865
DI 10.1126/science.7538697
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX850
UT WOS:A1995QX85000035
PM 7538697
ER

PT J
AU DONG, JT
   LAMB, PW
   RINKERSCHAEFFER, CW
   VUKANOVIC, J
   ICHIKAWA, T
   ISAACS, JT
   BARRETT, JC
AF DONG, JT
   LAMB, PW
   RINKERSCHAEFFER, CW
   VUKANOVIC, J
   ICHIKAWA, T
   ISAACS, JT
   BARRETT, JC
TI KAI1, A METASTASIS SUPPRESSOR GENE FOR PROSTATE-CANCER ON
   HUMAN-CHROMOSOME 11P11.2
SO SCIENCE
LA English
DT Article
ID TRANSMEMBRANE PROTEINS; SYNCYTIUM FORMATION; TUMOR PROGRESSION;
   MOLECULAR-CLONING; INCLUDING CD9; CELL-FUSION; ANTIGEN; FAMILY;
   IDENTIFICATION; ANTIBODY
AB A gene from human chromosome 11p11.2 was isolated and was shown to suppress metastasis when introduced into rat AT6.1 prostate cancer cells. Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors. KAI1 specifies a protein of 267 amino acids, with four hydrophobic and presumably transmembrane domains and one large extracellular hydrophilic domain with three potential N-glycosylation sites. KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins. Decreased expression of this gene may be involved in the malignant progression of prostate and other cancers.
C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709.
   JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231.
   CHIBA UNIV,SCH MED,DEPT UROL,CHIBA 260,JAPAN.
FU NCI NIH HHS [CA 58236]
NR 35
TC 643
Z9 757
U1 0
U2 9
PU AMER ASSOC ADVAN SCIENCE
PI WASHINGTON
PA 1333 H ST NW, WASHINGTON, DC 20005
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 12
PY 1995
VL 268
IS 5212
BP 884
EP 886
DI 10.1126/science.7754374
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX850
UT WOS:A1995QX85000041
PM 7754374
ER

PT J
AU TRACY, TS
   ROSENBLUTH, BW
   WRIGHTON, SA
   GONZALEZ, FJ
   KORZEKWA, KR
AF TRACY, TS
   ROSENBLUTH, BW
   WRIGHTON, SA
   GONZALEZ, FJ
   KORZEKWA, KR
TI ROLE OF CYTOCHROME-P450 2C9 AND AN ALLELIC VARIANT IN THE
   4'-HYDROXYLATION OF (R)-FLURBIPROFEN AND (S)-FLURBIPROFEN
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE FLURBIPROFEN; CYTOCHROME P450; HUMAN LIVER MICROSOMES; VACCINIA VIRUS;
   CDNA EXPRESSION; ENANTIOMERS
ID FLURBIPROFEN; PHARMACOKINETICS; HYDROXYLATION; INVITRO; CYP2C
AB Flurbiprofen is a chiral non-steroidal anti-inflammatory drug used in the treatment of pain or inflammation. The primary routes of biotransformation for (R)- and (S)-flurbiprofen are oxidation (presumably cytochrome P450) and conjugation. To date, the specific cytochrome P450 (P450) involved in the oxidative metabolism of this compound (specifically 4'-hydroxylation) has not been elucidated. Experiments were conducted to characterize the kinetic parameters (K-m and V-max) for the 4'-hydroxylation of (R)- and (S)-flurbiprofen in human liver microsomes, to determine if enantiomeric interactions occur when both enantiomers are present, and to identify the specific P450 form(s) involved in this reaction. In human liver microsomes, the K-m and V-max (mean +/- SD) for (R)-4'-hydroxy-flurbiprofen formation were 3.1 +/- 0.8 mu M and 305 +/- 168 pmol . min(-1). mg protein)(-1), respectively. In comparison, the K-m and V-max (mean +/- SD) for (S)-4'-hydroxy-flurbiprofen formation were 1.9 +/- 0.4 mu M and 343 +/- 196 pmol . min(-1). mg protein(-1), respectively. Enantiomeric interaction studies revealed a decrease in K-m and V-max for both enantiomers and an apparent loss of stereoselectivity. Racemic-warfarin, tolbutamide, alpha-naphthoflavone and erythromycin were studied as potential inhibitors of this process. The estimated K-i values for the inhibition of (R)- and (S)-4'-hydroxy-flurbiprofen formation by racemic-warfarin were 2.2 and 4.7 mu M. This reaction was also inhibited by tolbutamide. In contrast, erythromycin and alpha-naphthoflavone had no appreciable effect on 4'-hydroxy-flurbiprofen formation. cDNA expression of individual forms was used to determine which P450 was involved in 4'-hydroxy-flurbiprofen formation. P450 2C9 and an allelic variant (R144C) readily catalyzed the formation of 4'-hydroxy-flurbiprofen. P450 1A2 was also active albeit with a turnover rate 1/140th that of P450 2C9R144C (P450s 2C8, 2E1 and 3A4 were not active toward either enantiomer). The results of these studies indicate that the enantiomers of flurbiprofen may exhibit stereoselectivity with respect to enzyme affinity but have roughly equal maximum formation velocities. Additionally; these two enantiomers may compete for the enzyme resulting in lower maximum velocities for both enantiomers. Finally, of those P450 forms examined, only P450 2C9 and an allelic variant catalyzed the 4'-hydroxylation of both (R)- and (S)-flurbiprofen.
C1 ELI LILLY & CO,DEPT DRUG METAB & DISPOSIT,INDIANAPOLIS,IN 46285.
   NCI,BETHESDA,MD 20892.
RP TRACY, TS (reprint author), W VIRGINIA UNIV,SCH PHARM,DEPT BASIC PHARMACEUT SCI,HSN POB 9530,MORGANTOWN,WV 26506, USA.
FU NIDDK NIH HHS [N01-DK-6-2274]
NR 23
TC 88
Z9 89
U1 0
U2 6
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 MAY 11
PY 1995
VL 49
IS 9
BP 1269
EP 1275
DI 10.1016/0006-2952(95)00048-5
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA QZ298
UT WOS:A1995QZ29800012
PM 7763308
ER

PT J
AU LETEURTRE, F
   SACKETT, DL
   MADALENGOITIA, J
   KOHLHAGEN, G
   MACDONALD, T
   HAMEL, E
   PAULL, KD
   POMMIER, Y
AF LETEURTRE, F
   SACKETT, DL
   MADALENGOITIA, J
   KOHLHAGEN, G
   MACDONALD, T
   HAMEL, E
   PAULL, KD
   POMMIER, Y
TI AZATOXIN DERIVATIVES WITH POTENT AND SELECTIVE ACTION ON
   TOPOISOMERASE-II
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE TOPOISOMERASE II; TUBULIN; PODOPHYLLOTOXIN; AZATOXIN
ID ANTITUMOR AGENTS; TUBULIN POLYMERIZATION; ANILINO DERIVATIVES; KB CELLS;
   DNA; INHIBITORS; 4'-O-DEMETHYLEPIPODOPHYLLOTOXIN; PODOPHYLLOTOXIN;
   CYTOTOXICITY; CONGENERS
AB Azatoxin was rationally designed as a DNA topoisomerase II (top2) inhibitor [Leteurtre et al., Cancer Res 52: 4478-4483, 1992] and was also found to inhibit tubulin polymerization. Its cytotoxicity is due to action on tubulin at lower concentrations and on top2 at higher concentrations. At intermediate concentrations, the combination of the two mechanisms appears antagonistic [Solary et al., Biochem Pharmacol 45: 2449-2456, 1993]. The aim of this study was to design azatoxin derivatives that would act only on tubulin or on top2. Selective targeting of top2 or tubulin was tested using top2-mediated DNA cleavage assays, and tubulin polymerization and tubulin proteolysis assays, as well as COMPARE analyses of cytotoxicity assays in the National Cancer Institute in vitro Drug Screening Program. Selective inhibitors of top2 and tubulin polymerization have been obtained. Top2 inhibition, abolished by methylation at position 4', was enhanced by the addition of a bulky group at position 11. Bulky substitution at position 11 determined different patterns of top2 cleavage sites and suppressed the action on tubulin. Selective inhibition of tubulin was obtained with 4'-methylazatoxin that was found to bind to the colchicine site. These results are consistent with those obtained in the podophyllotoxin family to which azatoxin is structurally related. Some azatoxin derivatives are under consideration for further preclinical development.
C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892.
   NCI,DCT,DTP,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892.
   UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA.
NR 25
TC 41
Z9 42
U1 0
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 MAY 11
PY 1995
VL 49
IS 9
BP 1283
EP 1290
DI 10.1016/0006-2952(95)00047-4
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA QZ298
UT WOS:A1995QZ29800014
PM 7763310
ER

PT J
AU BRINKMANN, U
   CHOWDHURY, PS
   ROSCOE, DM
   PASTAN, I
AF BRINKMANN, U
   CHOWDHURY, PS
   ROSCOE, DM
   PASTAN, I
TI PHAGE DISPLAY OF DISULFIDE-STABILIZED FV FRAGMENTS
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE FV, DISULFIDE-STABILIZED; ANTI-TAC(FV); M13
ID SINGLE-CHAIN FV; RECOMBINANT IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN;
   ANTIBODY; LIBRARIES; PROTEINS; STRATEGY; SYSTEM
AB Phage display of single-chain Fvs (scFvs) is a powerful tool to enrich and isolate specific antibody fragments from large pools (libraries) of Fv coding genes. However, many scFvs and scFv fusion proteins are unstable, not only as soluble proteins but also on the surface of phage. This limits and biases the recovery of specific Fv phage from display libraries to relatively stable scFvs. Also, the peptide linker in scFvs can diminish antigen binding of scFvs and scFv-fusion proteins. Disulfide-stabilized Fvs (dsFv) which have the V-H-V-L heterodimer stabilized by an interchain disulfide bond connecting framework regions in V-H and V-L rather than a peptide linker are more stable than scFvs and in some instances show better binding. To analyze whether these advantages can be utilized in a phage display system and to prove the feasibility of dsFv display, we constructed phage for dsFv display of the anti-Tac antibody and a dsFv-phage library. We find that dsFv phage can specifically bind antigen although the titer of dsFv phage in supernatants appears to be reduced compared to scFv phage. But this reduction in titer does not hamper the isolation of dsFv phages from large pools (libraries) as demonstrated by 'panning' of anti-Tac scFv and dsFv phages on living leukemia cells in suspension. In addition, dsFv phage are more stable than scFv phage. Therefore, display of dsFvs on phage is a useful alternative and addition to scFv-phage display.
C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892.
NR 29
TC 30
Z9 33
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAY 11
PY 1995
VL 182
IS 1
BP 41
EP 50
DI 10.1016/0022-1759(95)00016-4
PG 10
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA QZ735
UT WOS:A1995QZ73500005
PM 7769243
ER

PT J
AU CRAMER, DW
   HARTGE, P
   NASCA, PC
   WHITTEMORE, AS
AF CRAMER, DW
   HARTGE, P
   NASCA, PC
   WHITTEMORE, AS
TI RISE OF OVARIAN-CANCER AFTER TREATMENT FOR INFERTILITY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NCI,ROCKVILLE,MD.
   UNIV MASSACHUSETTS,AMHERST,MA 01003.
   STANFORD UNIV,SCH MED,STANFORD,CA 94305.
RP CRAMER, DW (reprint author), BRIGHAM & WOMENS HOSP,75 FRANCIS ST,BOSTON,MA 02115, USA.
NR 2
TC 1
Z9 1
U1 0
U2 0
PU MASS MEDICAL SOC
PI BOSTON
PA 10 SHATTUCK, BOSTON, MA 02115
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 11
PY 1995
VL 332
IS 19
BP 1302
EP 1302
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW600
UT WOS:A1995QW60000016
ER

PT J
AU BAXEVANIS, AD
   LANDSMAN, D
AF BAXEVANIS, AD
   LANDSMAN, D
TI THE HMG-1 BOX PROTEIN FAMILY - CLASSIFICATION AND
   FUNCTIONAL-RELATIONSHIPS
SO NUCLEIC ACIDS RESEARCH
LA English
DT Review
ID MOBILITY-GROUP BOX; NONHISTONE CHROMOSOMAL PROTEIN; DNA-BINDING PROTEIN;
   TESTIS-DETERMINING GENE; TRANSCRIPTION FACTOR HUBF; SEX-DETERMINING
   REGION; AMINO-ACID-SEQUENCE; MATING-TYPE GENES; NUCLEOTIDE-SEQUENCE;
   CDNA CLONES
AB The abundant and highly-conserved nucleoproteins comprising the high mobility group-1/-2 (HMG-1/-2) family contains two homologous basic domains of about 75 amino acids, These basic domains, termed HMG-1 boxes, are highly structured and facilitate HMG-DNA interactions, Many proteins that regulate various cellular functions involving DNA binding and whose target DNA sequences share common structural characteristics have been identified as having an HMG-1 box; these proteins include the RNA polymerase I transcription factor UBF, the mammalian testis-determining factor SRY and the mitochondrial transcription factors ABF2 and mtTF1, among others, The sequences of 121 HMG-1 boxes have been compiled and aligned in accordance with thermodynamic results from homology model building (threading) experiments, basing the alignment on structure rather than by using traditional sequence homology methods. The classification of a representative subset of these proteins was then determined using standard least-squares distance methods, The proteins segregate into two groups, the first consisting of HMG-1/-2 proteins and the second consisting of proteins containing the HMG-1 box but which are not canonical HMG proteins, The proteins in the second group further segregate based on their function, their ability to bind specific sequences of DNA, or their ability to recognize discrete non-B-DNA structures, The HMG-1 box provides an excellent example of how a specific protein motif, with slight alteration, can be used to recognize DNA in a variety of functional contexts.
C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894.
RI Landsman, David/C-5923-2009; 
OI Landsman, David/0000-0002-9819-6675
NR 116
TC 167
Z9 173
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 11
PY 1995
VL 23
IS 9
BP 1604
EP 1613
DI 10.1093/nar/23.9.1604
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ477
UT WOS:A1995QZ47700024
PM 7784217
ER

PT J
AU BISANT, D
   MAIZEL, J
AF BISANT, D
   MAIZEL, J
TI IDENTIFICATION OF RIBOSOME BINDING-SITES IN ESCHERICHIA-COLI USING
   NEURAL-NETWORK MODELS
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN SECONDARY STRUCTURE; TRANSLATIONAL INITIATION SITES;
   MESSENGER-RNA; SEQUENCE; PREDICTION; GENE; EFFICIENCY; PROMOTERS;
   BACTERIOPHAGE; MUTATIONS
AB This study investigated the use of neural networks in the identification of Escherichia coli ribosome binding sites. The recognition of these sites based on primary sequence data is difficult due to the multiple determinants that define them. Additionally, secondary structure plays a significant role in the determination of the site and this information is difficult to include in the models. Efforts to solve this problem have so far yielded poor results. A new compilation of E.coli ribosome binding sites was generated for this study. Feedforward backpropagation networks were applied to their identification. Perceptrons were also applied, since they have been the previous best method since 1982. Evaluation of performance for all the neural networks and perceptrons was determined by ROC analysis. The neural network provided significant improvement in the recognition of these sites when compared with the previous best method, finding less than half the number of false positives when both models were adjusted to find an equal number of actual sites. The best neural network used an input window of 101 nucleotides and a single hidden layer of 9 units. Both the neural network and the perceptron trained on the new compilation performed better than the original perceptron published by Stormo et al. in 1982.
C1 NCI, FREDERICK CANC RES FACIL, FREDERICK, MD 21701 USA.
RP BISANT, D (reprint author), STANFORD UNIV, NEUROSCI PROGRAM 151 B, STANFORD, CA 94305 USA.
NR 50
TC 13
Z9 14
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 11
PY 1995
VL 23
IS 9
BP 1632
EP 1639
DI 10.1093/nar/23.9.1632
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ477
UT WOS:A1995QZ47700028
PM 7784221
ER

PT J
AU RAO, CN
   GOMEZ, DE
   WOODLEY, DT
   THORGEIRSSON, UP
AF RAO, CN
   GOMEZ, DE
   WOODLEY, DT
   THORGEIRSSON, UP
TI PARTIAL CHARACTERIZATION OF NOVEL SERINE PROTEINASE-INHIBITORS FROM
   HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
ID PLASMINOGEN-ACTIVATOR INHIBITOR; CAPILLARY-LIKE STRUCTURES; HUMAN
   SARCOMA-CELLS; EXTRACELLULAR-MATRIX; PROTEASE NEXIN; PURIFICATION;
   UROKINASE; TYPE-1; INVITRO; METALLOPROTEINASES
AB Serine proteinase inhibitors play major roles in physiological and pathophysiological processes such as angiogenesis, intravascular fibrinolysis, wound healing, and tumor invasion, and metastasis. Here, we report that human umbilical vein endothelial cells (HUVEC) synthesize three inhibitors (33,000, 31,000, and 27,000 Ha) which inhibit degradation of gelatin or casein by trypsin, elastase, plasmin, and alpha-chymotrypsin, The 33- and 31-kDa inhibitors were constitutively found in the cell lysate and extracellular matrix, but not in the conditioned medium of HUVEC, Following treatment with phorbol 12-myristate-13-acetate (PMA), all the three inhibitors were expressed in the CM and increased activity was found in cell lysates and extracellular matrix, The inhibitors were not detected in PMA-treated cells in the presence of cycloheximide or actinomycin D, The inhibitors specifically bound to trypsin and were recovered from trypsin affinity column as smaller-sized inhibitors without loss of antitrypsin activity, Polyclonal antibodies to inter-alpha-trypsin inhibitor did not cross-react with the 33-, 31-, and 27-kDa inhibitors, These results suggest that HUVEC synthesize and secrete novel 33-, 31-, and 27-kDa serine proteinase inhibitors. (C) 1995 Academic Press, Inc.
C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892.
RP RAO, CN (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT DERMATOL,303 E CHICAGO AVE,TARRY BLDG 4-714,CHICAGO,IL 60611, USA.
OI Gomez, Daniel E/0000-0002-8629-0787
NR 53
TC 37
Z9 37
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 MAY 10
PY 1995
VL 319
IS 1
BP 55
EP 62
DI 10.1006/abbi.1995.1266
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA QY750
UT WOS:A1995QY75000006
PM 7539605
ER

PT J
AU BROWN, DJ
   VANBENEDEN, RJ
   CLARK, GC
AF BROWN, DJ
   VANBENEDEN, RJ
   CLARK, GC
TI IDENTIFICATION OF 2 BINDING-PROTEINS FOR HALOGENATED
   AROMATIC-HYDROCARBONS IN THE HARD-SHELL CLAM, MERCENARIA-MERCENARIA
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE HALOGENATED AROMATIC HYDROCARBONS; MARINE; INVERTEBRATE; PHOTOAFFINITY
   LABEL; RECEPTOR; ARYL HYDROCARBON; TCDD; DIOXIN;
   TETRACHLORODIBENZO-P-DIOXIN
ID AH-RECEPTOR; RAINBOW-TROUT; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN;
   HERBICIDES; DIOXINS
AB Earlier studies have reported an unusually high incidence of gonadal tumors in marine bivalves in areas of potentially high exposure to herbicides including 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Some herbicides can be contaminated by halogenated aromatic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Most of the effects of planar halogenated aromatic compounds, including carcinogenic effects in vertebrates, appear to be mediated through binding to the aryl hydrocarbon receptor. The current study investigated whether halogenated aromatic hydrocarbon-binding proteins are present in the marine bivalve, Mercenaria mercenaria. We used the TCDD photoaffinity analog 2-azido-3-[I-125]-iodo-7,8-dibromodibenzo-p-dioxin to detect the presence of two proteins (28 and 39 kDa) in cytosols prepared from M. mercenaria that specifically bound this ligand. Expression of these proteins is tissue-dependent with the highest concentrations being observed in gill and gonadal tissue. Gonadal tissue also exhibited gender-specific expression with female clams exhibiting higher levels of the 39-kDa protein. Gender and tissue-specific expression are consistent with the hypothesis that these proteins might be involved in the carcinogenic response observed in clams exposed to herbicides. (C) 1995 Academic Press, Inc.
C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709.
   DUKE UNIV,DEPT CELL BIOL,DURHAM,NC 27710.
   UNIV MAINE,DEPT ZOOL,ORONO,ME 04469.
FU NCRR NIH HHS [R01 RR08774]
NR 26
TC 20
Z9 20
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 MAY 10
PY 1995
VL 319
IS 1
BP 217
EP 224
DI 10.1006/abbi.1995.1285
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA QY750
UT WOS:A1995QY75000025
PM 7771787
ER

PT J
AU GORDIS, E
   DUFOUR, MC
   WARREN, KR
   JACKSON, RJ
   FLOYD, RL
   HUNGERFORD, DW
AF GORDIS, E
   DUFOUR, MC
   WARREN, KR
   JACKSON, RJ
   FLOYD, RL
   HUNGERFORD, DW
TI SHOULD PHYSICIANS COUNSEL PATIENTS TO DRINK ALCOHOL
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341.
RP GORDIS, E (reprint author), NIAAA,BETHESDA,MD, USA.
NR 7
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 10
PY 1995
VL 273
IS 18
BP 1415
EP 1415
DI 10.1001/jama.273.18.1415
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW279
UT WOS:A1995QW27900011
PM 7723148
ER

PT J
AU LANDS, WEM
AF LANDS, WEM
TI ALCOHOL-CONSUMPTION AND TISSUE-TYPE PLASMINOGEN-ACTIVATOR
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
RP LANDS, WEM (reprint author), NIAAA,BETHESDA,MD, USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 10
PY 1995
VL 273
IS 18
BP 1416
EP 1416
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW279
UT WOS:A1995QW27900013
PM 7794364
ER

PT J
AU PSATY, BM
   KOEPSELL, TD
   YANEZ, ND
   SMITH, NL
   MANOLIO, TA
   HECKBERT, SR
   BORHANI, NO
   GARDIN, JM
   GOTTDIENER, JS
   RUTAN, GH
   SISCOVICK, DS
   FURBERG, CD
AF PSATY, BM
   KOEPSELL, TD
   YANEZ, ND
   SMITH, NL
   MANOLIO, TA
   HECKBERT, SR
   BORHANI, NO
   GARDIN, JM
   GOTTDIENER, JS
   RUTAN, GH
   SISCOVICK, DS
   FURBERG, CD
TI TEMPORAL PATTERNS OF ANTIHYPERTENSIVE MEDICATION USE AMONG OLDER ADULTS,
   1989 THROUGH 1992 - AN EFFECT OF THE MAJOR CLINICAL-TRIALS ON
   CLINICAL-PRACTICE
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CARDIOVASCULAR HEALTH; HIP FRACTURE; HYPERTENSION; DISEASE; RISK
AB Objective.-To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults.
   Design.-In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3.
   Results.-Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P=.04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P<.05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P=.03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P=.01) between period 1 (+6.7%) and period 3 (+2.8%).
   Conclusions.-Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.
C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98101.
   UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98101.
   UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98101.
   UNIV WASHINGTON,CTR CARDIOVASC HLTH STUDY COORDINATING,SEATTLE,WA 98101.
   NHLBI,BETHESDA,MD 20892.
   UNIV CALIF IRVINE,DIV CARDIOL,IRVINE,CA 92717.
   GEORGETOWN UNIV HOSP,DIV CARDIOL,WASHINGTON,DC 20007.
   VET ADM MED CTR,MEMPHIS,TN 38104.
   WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103.
RP PSATY, BM (reprint author), UNIV WASHINGTON,DEPT MED,CARDIOVASC HLTH RES UNIT,1730 MINOR AVE,SUITE 1360,SEATTLE,WA 98101, USA.
FU NHLBI NIH HHS [N01-HC-85080, H01-HC-85081, N01-HC-85079]
NR 23
TC 63
Z9 65
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 MAY 10
PY 1995
VL 273
IS 18
BP 1436
EP 1438
DI 10.1001/jama.273.18.1436
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW279
UT WOS:A1995QW27900031
PM 7723157
ER

PT J
AU GARG, R
   YUSUF, S
AF GARG, R
   YUSUF, S
TI OVERVIEW OF RANDOMIZED TRIALS OF ANGIOTENSIN-CONVERTING
   ENZYME-INHIBITORS ON MORTALITY AND MORBIDITY IN PATIENTS WITH
   HEART-FAILURE
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; LONG-TERM; EXERCISE PERFORMANCE;
   ENALAPRIL; LISINOPRIL; TOLERANCE; THERAPY
AB Objective.-To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure.
   Data Sources and Study Selection.-Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms.
   Data Extraction.-Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial, Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm.
   Data Synthesis.-The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88; P<.001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74; P<.001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant.
   Conclusions.-Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients.
C1 MCMASTER UNIV,HAMILTON GEN HOSP,DIV CARDIOL,HAMILTON,ON,CANADA.
RP GARG, R (reprint author), NHLBI,CLIN TRIALS BRANCH,FED BLDG,ROOM 5C10,BETHESDA,MD 20892, USA.
RI Jennings, Garry/B-3914-2009
NR 55
TC 1175
Z9 1214
U1 9
U2 38
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 MAY 10
PY 1995
VL 273
IS 18
BP 1450
EP 1456
DI 10.1001/jama.273.18.1450
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW279
UT WOS:A1995QW27900034
PM 7654275
ER

PT J
AU POLIS, MA
   MASUR, H
AF POLIS, MA
   MASUR, H
TI PROMISING NEW TREATMENTS FOR CYTOMEGALOVIRUS RETINITIS
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTRAVITREAL GANCICLOVIR; AIDS
   PATIENTS; FOSCARNET; EFFICACY; THERAPY
C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892.
RP POLIS, MA (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11C103,BETHESDA,MD 20892, USA.
OI Polis, Michael/0000-0002-9151-2268
NR 24
TC 19
Z9 19
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 MAY 10
PY 1995
VL 273
IS 18
BP 1457
EP 1459
DI 10.1001/jama.273.18.1457
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW279
UT WOS:A1995QW27900035
PM 7723160
ER

PT J
AU KOST, RG
   KUPINSKY, H
   STRAUS, SE
AF KOST, RG
   KUPINSKY, H
   STRAUS, SE
TI VARICELLA-ZOSTER VIRUS GENE-63 - TRANSCRIPT MAPPING AND REGULATORY
   ACTIVITY
SO VIROLOGY
LA English
DT Note
ID MESSENGER-RNA; DNA; EXPRESSION; CELLS; GENOME; PROMOTERS; SEQUENCE;
   PROTEIN; LATENCY; SITE
AB The varicella-zoster virus (VZV) putative immediate-early (IE) protein encoded by ORF63 is the homolog of HSV-1 ICP-22. To further characterize ORF63 and its function, Northern analysis, primer extension, and S1 nuclease assays were used to map its transcripts, and transient transfection assays were performed with constructs containing ORF63 or its promoter region. Two transcripts were identified: a 0.9-kb transcript spans ORF63 alone, and a 1.8-kb transcript reads through ORF64. Two prominent transcription start sites were identified at -88 and -157 relative to the ORF63 ATG, and two potential TATA elements were identified. In transient transfection assays, the 63 promoter was weakly activated by VN ORF4 and ORF62 under their homologous promoters, was more strongly activated by ORF62 under the control of a constitutive CMV promoter, and was synergistically activated by ORFs 4 and 62 together. ORF63, driven by its own or by a heterologous SV40 promoter, exerted minimal effects on diverse VN putative IE and early promoters, showed no clear evidence of autoregulation, and did not directly inhibit the ORF62 promoter as had been reported previously. ORF63's behavior in transient assays suggests that it plays only a limited regulatory role in modulating VZV gene expression.
RP KOST, RG (reprint author), NIAID,LCI,MED VIROL SECT,BLDG 10,ROOM 11N228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 32
TC 49
Z9 51
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 0042-6822
J9 VIROLOGY
JI Virology
PD MAY 10
PY 1995
VL 209
IS 1
BP 218
EP 224
DI 10.1006/viro.1995.1246
PG 7
WC Virology
SC Virology
GA QY819
UT WOS:A1995QY81900023
PM 7747473
ER

PT J
AU HOSHINO, Y
   SAIF, LJ
   KANG, SY
   SERENO, MM
   CHEN, WK
   KAPIKIAN, AZ
AF HOSHINO, Y
   SAIF, LJ
   KANG, SY
   SERENO, MM
   CHEN, WK
   KAPIKIAN, AZ
TI IDENTIFICATION OF GROUP-A ROTAVIRUS GENES ASSOCIATED WITH VIRULENCE OF A
   PORCINE ROTAVIRUS AND HOST-RANGE RESTRICTION OF A HUMAN ROTAVIRUS IN THE
   GNOTOBIOTIC PIGLET MODEL
SO VIROLOGY
LA English
DT Note
ID GUANYLYLTRANSFERASE ACTIVITY; REASSORTANT ROTAVIRUSES; NEUTRALIZATION;
   VP3; BOVINE; STRAIN; SPECIFICITIES; VOLUNTEERS; INFECTION; CHILDREN
AB Rotaviruses are the leading cause of severe diarrhea in infants and young children worldwide. Thus, the development of an effective rotavirus vaccine is a major public health goal. This study was performed to identify the gene or genes responsible for rotavirus virulence or host range restriction and attenuation in a natural host. Such knowledge could have an important bearing on the selection of candidate live vaccine strains. We addressed this issue by analyzing the response of gnotobiotic piglets to orally administered porcine x human rotavirus reassortants. It was possible to determine (i) which porcine rotavirus genes were required for the induction of diarrhea, and (ii) which human rotavirus genes are associated with the host range restriction because the parental porcine rotavirus (SB-1A strain) caused diarrhea in piglets, whereas the parental human rotavirus (DS-I strain) was attenuated in piglets. Substitution of the 3rd (VP3) or 4th (VP4) or 9th (VP7) or 10th (NS28 (NSP4)) gene of the avirulent human strain for the corresponding gene of porcine rotavirus that was virulent for gnotobiotic piglets yielded viral reassortants that failed to induce diarrhea. Further analysis indicated that reassortants which possessed only one, two, or three of these porcine rotavirus genes on a background of human rotavirus genes also failed to induce diarrhea. However, diarrhea was induced when all four of these porcine rotavirus genes were included in a reassortant in which the remaining seven genes were derived from the human rotavirus. These observations suggest that it may be possible to attenuate wild-type human rotavirus strains that are virulent for humans by selective genetic reassortment with an animal rotavirus strain that is attenuated for humans. (C) 1995 Academic Press, Inc.
C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,WOOSTER,OH 44691.
RP HOSHINO, Y (reprint author), NIAID,INFECT DIS LAB,EPIDEMIOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 37
TC 119
Z9 126
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 0042-6822
J9 VIROLOGY
JI Virology
PD MAY 10
PY 1995
VL 209
IS 1
BP 274
EP 280
DI 10.1006/viro.1995.1255
PG 7
WC Virology
SC Virology
GA QY819
UT WOS:A1995QY81900032
PM 7747480
ER

PT J
AU MORIUCHI, H
   MORIUCHI, M
   DEAN, H
   CHEUNG, AK
   COHEN, JI
AF MORIUCHI, H
   MORIUCHI, M
   DEAN, H
   CHEUNG, AK
   COHEN, JI
TI PSEUDORABIES VIRUS EPO IS FUNCTIONALLY HOMOLOGOUS TO VARICELLA-ZOSTER
   VIRUS ORF61 PROTEIN AND HERPES-SIMPLEX VIRUS TYPE-1 ICPO
SO VIROLOGY
LA English
DT Note
ID OPEN READING FRAME; IMMEDIATE-EARLY PROTEIN; COMPLETE DNA-SEQUENCE;
   EARLY GENE; PROMOTERS; RECOMBINANT; EXPRESSION; DELETION; MUTANTS; CELLS
AB Pseudorabies virus (PRV) early protein 0 (EP0) is the homolog of varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein and herpes simplex virus type 1 (HSV-1) ICP0. A PRV EP0 deletion mutant grows poorly in cell culture, suggesting that EP0 plays a critical role in the viral replicative cycle, In this study, we have shown that the growth defect of an EP0 deletion mutant was complemented in Vero cells expressing VZV ORF61 protein or HSV-1 ICP0. In transient expression assays PRV EP0, like VZV ORF61 protein and HSV-1 ICP0, transactivates a variety of promoters from PRV, VZV, HSV, and unrelated viruses. These data indicate that PRV EP0 is functionally homologous to VZV ORF61 protein and HSV-1 ICP0. (C) 1995 Academic Press, Inc.
C1 USDA,NATL ANIM DIS CTR,VIROL SWINE RES UNIT,AMES,IA 50010.
RP MORIUCHI, H (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 30
TC 19
Z9 20
U1 0
U2 0
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAY 10
PY 1995
VL 209
IS 1
BP 281
EP 283
DI 10.1006/viro.1995.1256
PG 3
WC Virology
SC Virology
GA QY819
UT WOS:A1995QY81900033
PM 7747481
ER

PT J
AU CHANG, EY
   MAO, SY
   METZGER, H
   HOLOWKA, D
   BAIRD, B
AF CHANG, EY
   MAO, SY
   METZGER, H
   HOLOWKA, D
   BAIRD, B
TI EFFECTS OF SUBUNIT MUTATION ON THE ROTATIONAL-DYNAMICS OF FC-EPSILON-RI,
   THE HIGH-AFFINITY RECEPTOR FOR IGE, IN TRANSFECTED CELLS
SO BIOCHEMISTRY
LA English
DT Article
ID EPIDERMAL LANGERHANS CELLS; BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E;
   MAST-CELLS; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION;
   MONOCLONAL-ANTIBODIES; CYTOPLASMIC DOMAINS; HISTAMINE-RELEASE;
   GAMMA-RIII
AB Erythrosin-labeled immunoglobulin E (IgE) and time-resolved phosphorescence anisotropy were used to monitor the rotational dynamics of transfected wild-type (alpha beta gamma(2)) and four mutant Fc epsilon RI receptors in the monomeric and dimeric state on P815 cells. Erythrosin-IgE bound to Fc epsilon RI on cells transfected with either beta or gamma subunits with truncated COOH-terminal cytoplasmic segments exhibit faster rotational motion than when bound to Fc epsilon RI on cells transfected with wild-type subunits. Deletion of the NH2-terminal cytoplasmic segment of the beta subunit or the COOH-tenninal cytoplasmic segment of the alpha subunit does not cause any significant change in the anisotropy decay. Dimers of IgE-receptor complexes formed with anti-IgE monoclonal antibody B1E3 exhibit substantially slower anisotropy decays for all the receptor constructs used, including a receptor construct that only contains the ectodomain of the alpha subunit anchored to Chinese hamster ovary (CHO) cell membranes through a lipid tail. This loss of rotational motion of dimeric IgE-Fc epsilon RI complexes may be due to nonspecific entanglement or to specific interactions involving IgE or the extracellular portion of alpha. The results suggest that the beta and gamma subunits of the tetrameric alpha beta gamma(2) receptor participate in interactions with other membrane components even in the absence of receptor aggregation. The loss of such interactions may be related to the functional impairments previously determined for these mutants.
C1 CORNELL UNIV, DEPT CHEM, ITHACA, NY 14853 USA.
   NIAMS, ARTHRIT & RHEUMAT BRANCH, CHEM IMMUNOL SECT, BETHESDA, MD 20892 USA.
FU NIAID NIH HHS [AI18306, AI22449]
NR 47
TC 2
Z9 2
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 9
PY 1995
VL 34
IS 18
BP 6093
EP 6099
DI 10.1021/bi00018a012
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX567
UT WOS:A1995QX56700012
PM 7742313
ER

PT J
AU ZHUO, SQ
   FAN, SJ
   HUANG, S
   KAUFMAN, S
AF ZHUO, SQ
   FAN, SJ
   HUANG, S
   KAUFMAN, S
TI STUDY OF THE ROLE OF RETINOBLASTOMA PROTEIN IN TERMINAL DIFFERENTIATION
   OF MURINE ERYTHROLEUKEMIA-CELLS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID GENE-PRODUCT; TRANSCRIPTION FACTOR; CYCLE PROGRESSION; BINDING;
   EXPRESSION; KINASE; PHASE; G1; DEPHOSPHORYLATION; PHOSPHORYLATION
AB Hexamethylenebisacetamide-induced terminal differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells can be inhibited by okadaic acid, an inhibitor of type 1 and type 2A protein phosphatases. The inhibition is shown to be correlated with prevention of dephosphorylation of retinoblastoma protein (pRB) in cells and bypass of G(1) prolongation in the cell cycle, These results suggest that pRB-mediated G(1) prolongation is necessary for MEL cells to commit to terminal differentiation. However, further experiments demonstrate that the simple cell cycle exit is not sufficient for commitment to terminal differentiation, Induction of dephosphorylation of pRB and subsequent G(1) prolongation by forskolin does not lead MEL cells to differentiate, Additional PRE has been expressed in MEL cells by transfection with a neo-resistant plasmid containing RE cDNA under the control of a cytomegalovirus promoter. Exogenously expressed pRB is hyperphosphorylated in logarithmically growing MEL cells without any noticeable change in growth rate between the transfected cell line and the parental cell line. This result suggests that pRB in MEL cells is regulated by protein kinases and protein phosphatases and not by transcription.
C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892.
   LA JOLLA CANC RES FDN,CANC RES CTR,LA JOLLA,CA 92093.
RP ZHUO, SQ (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA.
FU NCI NIH HHS [CA57496]
NR 36
TC 23
Z9 24
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 MAY 9
PY 1995
VL 92
IS 10
BP 4234
EP 4238
DI 10.1073/pnas.92.10.4234
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600031
PM 7753788
ER

PT J
AU FLOWERS, KM
   KIMBALL, SR
   FELDHOFF, RC
   HINNEBUSCH, AG
   JEFFERSON, LS
AF FLOWERS, KM
   KIMBALL, SR
   FELDHOFF, RC
   HINNEBUSCH, AG
   JEFFERSON, LS
TI MOLECULAR-CLONING AND CHARACTERIZATION OF CDNA-ENCODING THE
   ALPHA-SUBUNIT OF THE RAT PROTEIN-SYNTHESIS INITIATION-FACTOR EIF-2B
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID GUANINE-NUCLEOTIDE-EXCHANGE; POLYPEPTIDE-CHAIN INITIATION; AMINO-ACID
   AVAILABILITY; FACTOR-II; TRANSLATIONAL CONTROL;
   SACCHAROMYCES-CEREVISIAE; GCN4 EXPRESSION; GTP-BINDING; PHOSPHORYLATION;
   YEAST
AB Eukaryotic initiation factor 2B (eIF-2B) is an essential component of the pathway of peptide-chain initiation in mammalian cells, yet little is known about its molecular structure and regulation, To investigate the structure, regulation, and interactions of the individual subunits of eIF-2B, we have begun to clone, characterize, and express the corresponding cDNAs, We report here the cloning and characterization of a 1510-bp cDNA encoding the alpha subunit of eIF-2B from a rat brain cDNA library, The cDNA contains an open reading frame of 918 bp encoding a polypeptide of 305 aa with a predicted molecular mass of 33.7 kDa, This cDNA recognizes a single RNA species approximate to 1.6 kb in length on Northern blots of RNA from rat liver, The predicted amino acid sequence contains regions identical to the sequences of peptides derived from bovine liver eIF-2B alpha subunit, Expression of this cDNA in vitro yields a peptide which comigrates with natural eIF-2B alpha in SDS/polyacrylamide gels, The predicted amino acid sequence exhibits 42% identity to that deduced for the Saccharomyces cerevisiae GCN3 protein, the smallest subunit of yeast eIF-2B. In addition, expression of the rat cDNA in yeast functionally complements a gcn3 deletion for the inability to induce histidine biosynthetic genes under the control of GCN4. These results strongly support the hypothesis that mammalian eIF-2 alpha and GCN3 are homologues, Southern blots indicate that the eIF-2B alpha cDNA also recognizes genomic DNA fragments from several other species, suggesting significant homology between the rat eIF-2B alpha gene and that from other species.
C1 UNIV LOUISVILLE,SCH MED,DEPT BIOCHEM,LOUISVILLE,KY 40292.
   NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892.
RP FLOWERS, KM (reprint author), PENN STATE UNIV,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,POB 850,HERSHEY,PA 17033, USA.
FU NIDDK NIH HHS [DK13499, DK15658]
NR 34
TC 10
Z9 11
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 MAY 9
PY 1995
VL 92
IS 10
BP 4274
EP 4278
DI 10.1073/pnas.92.10.4274
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600039
PM 7753796
ER

PT J
AU XU, LC
   KARLSSON, S
   BYRNE, ER
   KLUEPFELSTAHL, S
   KESSLER, SW
   AGRICOLA, BA
   SELLERS, S
   KIRBY, M
   DUNBAR, CE
   BRADY, RO
   NIENHUIS, AW
   DONAHUE, RE
AF XU, LC
   KARLSSON, S
   BYRNE, ER
   KLUEPFELSTAHL, S
   KESSLER, SW
   AGRICOLA, BA
   SELLERS, S
   KIRBY, M
   DUNBAR, CE
   BRADY, RO
   NIENHUIS, AW
   DONAHUE, RE
TI LONG-TERM IN-VIVO EXPRESSION OF THE HUMAN GLUCOCEREBROSIDASE GENE IN
   NONHUMAN-PRIMATES AFTER CD34(+) HEMATOPOIETIC-CELL TRANSDUCTION WITH
   CELL-FREE RETROVIRAL VECTOR PREPARATIONS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID BONE-MARROW TRANSPLANTATION; GAUCHER DISEASE; STEM-CELLS; PROGENITOR
   CELLS; REPLACEMENT THERAPY; ADENOSINE-DEAMINASE; RECONSTITUTED MICE;
   HOST RANGES; INTERLEUKIN-3; MACROPHAGES
AB Successful gene transfer into stem cells would provide a potentially useful therapeutic modality for treatment of inherited and acquired disorders affecting hematopoietic tissues. Coculture of primate bone marrow cells with retroviral producer cells, autologous stroma, or an engineered stromal cell line expressing human stem cell factor has resulted in a low efficiency of gene transfer as reflected by the presence of 0.1-5% of genetically modified cells in the blood of reconstituted animals. Our experiments in a nonhuman primate model were designed to explore various transduction protocols that did not involve coculture in an effort to define clinically useful conditions and to enhance transduction efficiency of repopulating cells. We report the presence of genetically modified cells at levels ranging from 0.1% (granulocytes) to 14% (B lymphocytes) more than 1 year following reconstitution of myeloablated animals with CD34(+) immunoselected cells transduced in suspension culture with cytokines for 4 days with a retrovirus containing the glucocerebrosidase gene. A period of prestimulation for 7 days in the presence of autologous stroma separated from the CD34(+) cells by a porous membrane did not appear to enhance transduction efficiency. Infusion of transduced CD34(+) cells into animals without myeloablation resulted in only transient appearance of genetically modified cells in peripheral blood. Our results document that retroviral transduction of primate repopulating cells can be achieved without coculture with stroma or producer cells and that the proportion of genetically modified cells may be highest in the B-lymphoid lineage under the given transduction conditions.
C1 NHLBI, HEMATOL BRANCH, ROCKVILLE, MD 20850 USA.
   NINCDS, DEV & METAB NEUROL BRANCH, BETHESDA, MD 20892 USA.
   NATL NAVAL MED CTR, IMMUNE CELL BIOL PROGRAM, BETHESDA, MD 20889 USA.
NR 35
TC 64
Z9 64
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4372
EP 4376
DI 10.1073/pnas.92.10.4372
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600059
PM 7538667
ER

PT J
AU SUZUKI, H
   ROMANOSPICA, V
   PAPAS, TS
   BHAT, NK
AF SUZUKI, H
   ROMANOSPICA, V
   PAPAS, TS
   BHAT, NK
TI ETS1 SUPPRESSES TUMORIGENICITY OF HUMAN COLON-CANCER CELLS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE TRANSCRIPTION FACTOR
ID SEQUENCE-SPECIFIC BINDING; LONG TERMINAL REPEAT; DNA-BINDING; C-ETS;
   TRANSCRIPTIONAL ACTIVATION; MONOCLONAL-ANTIBODY; GENE FAMILY; PROTEIN;
   EXPRESSION; DOMAIN
AB We have ectopically expressed transcription factor ETS1 in two different highly tumorigenic human colon cancer cell lines, DLD-1 and HCT116, that do not express endogenous ETS1 protein and have obtained several independent clones. The expression of wild-type ETS1 protein in these colon cancer cells reverses the transformed phenotype and tumorigenicity in a dose-dependent manner. By contrast, expression in DLD-1 cells of a variant form of ETS1, lacking transcriptional activity, did not alter the tumorigenic properties of the cells, suggesting that the reduction in tumorigenicity in these clones was specific for the wild-type ETS1 gene products. Since these colon cancer cells have multiple genetic alterations, the system described in this paper could be a good model to study-the Suppression of tumorigenicity at a transcriptional level, which could lead to the design and development of novel drugs for cancer treatment.
C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702.
   MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOLEC & STRUCT BIOL,CHARLESTON,SC 29425.
   PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702.
NR 38
TC 37
Z9 38
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4442
EP 4446
DI 10.1073/pnas.92.10.4442
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600073
PM 7753825
ER

PT J
AU BORNSTEIN, P
   MCKINNEY, CE
   LAMARCA, ME
   WINFIELD, S
   SHINGU, T
   DEVARAYALU, S
   VOS, HL
   GINNS, EI
AF BORNSTEIN, P
   MCKINNEY, CE
   LAMARCA, ME
   WINFIELD, S
   SHINGU, T
   DEVARAYALU, S
   VOS, HL
   GINNS, EI
TI METAXIN, A GENE CONTIGUOUS TO BOTH THROMBOSPONDIN-3 AND
   GLUCOCEREBROSIDASE, IS REQUIRED FOR EMBRYONIC-DEVELOPMENT IN THE MOUSE -
   IMPLICATIONS FOR GAUCHER-DISEASE
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE HOMOLOGOUS RECOMBINATION; GENE TARGETING; EMBRYONIC STEM CELLS
ID MESSENGER-RNA; ANTISENSE; TRANSCRIPTION; DISRUPTION; PROMOTER; MURINE;
   LOCUS; EXPRESSION; MUTATIONS; ELEMENTS
AB We have identified a murine gene, metaxin, that spans the 6-kb interval separating the glucocerebrosidase gene (GC) from the thrombospondin 3 gene on chromosome 3E3-F1. Metaxin and GC are transcribed convergently; their major polyadenylylation sites are only 431 bp apart. On the other hand, metaxin and the thrombospondin 3 gene are transcribed divergently and share a common promoter sequence. The cDNA for metaxin encodes a 317-aa protein, without either a signal sequence or consensus for N-linked glycosylation. Metaxin protein is expressed ubiquitously in tissues of the young adult mouse, but no close homologues have been found in the DNA or protein data bases. A targeted mutation (A --> G in exon 9) was introduced into GC by homologous recombination in embryonic stem cells to establish a mouse model for a mild form of Gaucher disease. A phosphoglycerate kinase-neomycin gene cassette was also inserted into the 3'-flanking region of GC as a selectable marker, at a site later identified as the terminal exon of metaxin. Mice homozygous for the combined mutations die early in gestation. Since the same amino acid mutation in humans is associated with mild type 1 Gaucher disease, we suggest that metaxin protein is likely to be essential for embryonic development in mice, Clearly, the contiguous gene organization at this locus limits targeting strategies for the production of murine models of Gaucher disease.
C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892.
   NETHERLANDS CANC INST,DEPT TUMOR BIOL,1066 CX AMSTERDAM,NETHERLANDS.
RP BORNSTEIN, P (reprint author), UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA 98195, USA.
FU NIDCR NIH HHS [DE 08229]
NR 32
TC 48
Z9 49
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4547
EP 4551
DI 10.1073/pnas.92.10.4547
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600094
PM 7753840
ER

PT J
AU GOOD, PJ
AF GOOD, PJ
TI A CONSERVED FAMILY OF ELAV-LIKE GENES IN VERTEBRATES
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID RNA-BINDING PROTEINS; DROSOPHILA-MELANOGASTER; NERVOUS-SYSTEM;
   XENOPUS-LAEVIS; MESSENGER-RNA; LOCUS ELAV; EXPRESSION; NEURONS; ANTIGEN;
   IDENTIFICATION
AB A large family of genes encodes proteins with RNA recognition motifs that are presumed to bind RNA and to function in posttranscriptional regulation. Neural-specific members of this family include elav, a gene required for correct differentiation and maintenance of neurons in Drosophila melanogaster, and a related gene, HuD, which is expressed in human neuronal cells. I have identified genes related to elav and HuD in Xenopus laevis, zebrafish, and mouse that define a family of four closely related vertebrate elav-like genes (elrA, elrB, elrC, and elrD) in fish, frogs, and mammals. In addition to protein sequence conservation, a segment of the 3'-untranslated sequence of elrD is also conserved, implying a functional role in elrD expression. In adult frogs, elrC and elrD are exclusively expressed in the brain, whereas elrB is expressed in brain, testis, and ovary, During Xenopus development, elrC and elrD RNAs are detected by late gastrula and late neurula stages, respectively, whereas a nervous system-specific elrB RNA species is expressed by early tadpole stage. Additional elrB transcripts are detected in the ovary and early embryo, demonstrating a maternal supply of mRNA and possibly of protein These expression patterns suggest a role for different elav-like genes in early development and neuronal differentiation. Surprisingly, elrA is expressed in all adult tissues tested and at all times during development. Thus, the widely expressed elrA is expected to have a related function in ail cells.
C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892.
NR 41
TC 234
Z9 240
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4557
EP 4561
DI 10.1073/pnas.92.10.4557
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600096
PM 7753842
ER

PT J
AU KWAK, HS
   YIM, HS
   CHOCK, PB
   YIM, MB
AF KWAK, HS
   YIM, HS
   CHOCK, PB
   YIM, MB
TI ENDOGENOUS INTRACELLULAR GLUTATHIONYL RADICALS ARE GENERATED IN
   NEUROBLASTOMA-CELLS UNDER HYDROGEN-PEROXIDE OXIDATIVE STRESS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE FREE RADICAL; SPIN TRAPPING; ELECTRON PARAMAGNETIC RESONANCE;
   GLUTATHIONE; N-ACETYL-L-CYSTEINE
ID NF-KAPPA-B; HUMAN-IMMUNODEFICIENCY-VIRUS; ELECTRON-SPIN-RESONANCE; ZINC
   SUPEROXIDE-DISMUTASE; TRANSCRIPTION FACTOR; OXYGEN; ACTIVATION;
   RADIOLYSIS; BINDING; AGENTS
AB We report the detection of endogenous intracellular glutathionyl (GS(.)) radicals in the intact neuroblastoma cell line NCB-20 under oxidative stress. Spin-trapping and electron paramagnetic resonance (EPR) spectroscopic methods were used for monitoring the radicals. The cells incubated with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) were challenged with H2O2 generated by the enzymic reaction of glucose/glucose oxidase. These cells exhibit the EPR spectrum of the GS(.) radical adduct of DMPO (DMPO-(.)SG) without exogenous reduced glutathione (GSH). The identity of this radical adduct was confirmed by observing hyperfine coupling constants identical to previously reported values in in vitro studies, which utilized known enzymic reactions, such as horseradish peroxidase and Cu/Zn superoxide dismutase, with GSH and H2O2 as substrates. The formation of the GS(.) radicals required viable cells and continuous biosynthesis of GSH. No significant effect on the resonance amplitude by the addition of a membrane-impermeable paramagnetic broadening agent indicated that these radicals were located inside the intact cell. N-Acetyl-L-cysteine (NAC)-treated cells produced NAC derived free radicals (NAC(.)) in place of GS(.) radicals, The time course studies showed that DMPO-(.)SG formation exhibited a large increase in its concentration after a lag period, whereas DMPO-NAGC(.) formation from NAG-treated cells did not show this sudden increase. These results were discussed in terms of the limit of antioxidant enzyme defenses in cells and the potential role of the GS(.) radical burst in activation of the transcription nuclear factor NF-kappa B in response to oxidative stress.
C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892.
NR 39
TC 33
Z9 33
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4582
EP 4586
DI 10.1073/pnas.92.10.4582
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600101
PM 7753847
ER

PT J
AU ORLIC, D
   ANDERSON, S
   BIESECKER, LG
   SORRENTINO, BP
   BODINE, DM
AF ORLIC, D
   ANDERSON, S
   BIESECKER, LG
   SORRENTINO, BP
   BODINE, DM
TI PLURIPOTENT HEMATOPOIETIC STEM-CELLS CONTAIN HIGH-LEVELS OF
   MESSENGER-RNA FOR C-KIT, GATA-2, P45 NF-E2, AND C-MYB AND LOW-LEVELS OR
   NO MESSENGER-RNA FOR C-FMS AND THE RECEPTORS FOR
   GRANULOCYTE-COLONY-STIMULATING FACTOR AND INTERLEUKIN-5 AND
   INTERLEUKIN-7
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE GROWTH FACTOR RECEPTORS; TRANSCRIPTION FACTORS; GENE EXPRESSION
ID ERYTHROID TRANSCRIPTION FACTOR; MEDIATED GENE-TRANSFER; ERYTHROPOIETIN
   RECEPTOR; GROWTH-FACTOR; EXPRESSION; DIFFERENTIATION; PROTEIN; MICE;
   PURIFICATION; COMMITMENT
AB Pluripotent hematopoietic stem cells (PHSCs) were highly enriched from mouse bone marrow by counterflow centrifugal elutriation, lineage subtraction, and fluorescence-activated cell sorting based on high c-kit receptor expression (C-kit(BR)). We used reverse transcriptase polymerase chain reaction to assay the C-kit(BR) subset and the subsets expressing low (C-kit(DULL)) and no (c-kit(NEG)) c-kit receptor for expression of mRNA encoding hematopoietic growth factor receptors and transcription factors. The c-kit(BR) cells had approximate to 3.5-fold more c-kit mRNA than unfractionated bone marrow cells, The C-kit(DULL) cells had 47-58% of the c-kit mRNA found in C-kit(BR) cells and the C-kit(NEG) cells had 4-9% of the c-kit mRNA present in C-kit(BR) cells, By comparing mRNA levels in C-kit(BR) cells (enriched for PHSCs) with those of unfractionated bone marrow, we demonstrated that C-Kit(BR) cells contained low or undetectable levels of mRNA for c-fms, granulocyte colony-stimulating factor receptor, interleukin 5 receptor (IL-5R), and IL-7R These same cells had moderate levels of mRNA for erythropoietin receptor, IL-3R subunits IL-3R alpha (SUT-1), AIC-2A, and AIC-2B, IL-6R and its partner gp-130, and the transcription factor GATA-1 and high levels of mRNA for transcription factors GATA-2 p45 NF-E2, and c-myb. We conclude from these Endings that PHSCs are programed to interact with stem cell factor, IL-3, and IL-6 but not with granulocyte or macrophage colony-stimulating factor, These findings also indicate that GATA-2, p45 NE-E2, and c-myb activities may be involved in PNSC maintenance or proliferation.
C1 NIH, NATL CTR HUMAN GENOME RES, GENET DIS RES LAB, BETHESDA, MD 20892 USA.
   NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA.
   ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA.
   ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA.
RP ORLIC, D (reprint author), NIH, NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB, HEMATOPOIESIS SECT,BLDG 49, ROOM 3W16, BETHESDA, MD 20892 USA.
NR 40
TC 132
Z9 133
U1 3
U2 4
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 MAY 9
PY 1995
VL 92
IS 10
BP 4601
EP 4605
DI 10.1073/pnas.92.10.4601
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600105
PM 7538677
ER

PT J
AU TAKAHASHI, S
   DRISCOLL, BF
   LAW, MJ
   SOKOLOFF, L
AF TAKAHASHI, S
   DRISCOLL, BF
   LAW, MJ
   SOKOLOFF, L
TI ROLE OF SODIUM AND POTASSIUM-IONS IN REGULATION OF GLUCOSE-METABOLISM IN
   CULTURED ASTROGLIA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE [C-14] DEOXYGLUCOSE; NA+,K+-ATPASE; GLUTAMATE; ASTROCYTE
ID RAT-BRAIN; ENERGY-METABOLISM; ELECTRICAL-STIMULATION; GLUTAMATE
   TRANSPORTER; DEOXYGLUCOSE UPTAKE; EXTRACELLULAR K+; ATPASE ACTIVITY;
   CELLULAR-LEVEL; ASTROCYTES; EXPRESSION
AB Effects of increasing extracellular K+ or intracellular Na+ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined, Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [C-14]deoxyglucose ([C-14]dGlc), and 5.4, 28, or 56 mM KCI for 10, 15, or 30 min, and then for 5 min in [C-14]dGlc-free buffer to allow efflux of unmetabolized [C-14]dGlc. Cells were then digested and assayed for labeled products, which were shown to consist of 96-98% [C-14] deoxyglucose 6-phosphate. Increased K+ concentrations significantly raised [C-14]deoxyglucose 6-phosphate accumulation in both neuronal and mixed neuronal-astroglial cultures at 15 and 30 min but did not raise it in astroglial cultures, Veratridine (75 mu M), which opens voltage-dependent Na+ channels, significantly raised rates of [C-14]dGlc phosphorylation in astroglial cultures (+20%), and these elevations were blocked by either 1 mM ouabain, a specific inhibitor of Na+, K+-ATPase (EC 3.6.1.37), or 10 mu M tetrodotoxin, which blocks Na+ channels, The carboxylic sodium ionophore, monensin (10 mu M), more than doubled [C-14]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 mu M) also stimulated [C-14]dGlc phosphorylation in astroglia-not through N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor mechanisms but via a Na+-dependent glutamate-uptake system, These results indicate that increased uptake of Na+ can stimulate energy metabolism in astroglial cells.
C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892.
RI Takahashi, Shinichi/L-3454-2013
NR 49
TC 135
Z9 136
U1 1
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4616
EP 4620
DI 10.1073/pnas.92.10.4616
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600108
PM 7753851
ER

PT J
AU RICHARDSON, J
   CVEKL, A
   WISTOW, G
AF RICHARDSON, J
   CVEKL, A
   WISTOW, G
TI PAX-6 IS ESSENTIAL FOR LENS-SPECIFIC EXPRESSION OF ZETA-CRYSTALLIN
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID HOMEOBOX-CONTAINING GENE; GUINEA-PIG; MUTATIONS; CELLS
AB Pax-6 is essential for normal eye development and has been implicated as a ''master gene'' for lens formation in embryogenesis. Guinea pig zeta-crystallin, a taxon-specific enzyme crystallin, achieves high expression specifically in lens through use of an alternative promoter. Here we show that Pax-6 binds a site in this promoter, which is essential for lens-specific expression. Lens and lens-derived cells exhibit a tissue-specific pattern of alternative splicing of Pax-6 transcripts and Pax-6 is expressed in adult lenses and cells that support zeta-crystallin expression. These results suggest that zeta-crystallin is a natural target gene for Pax-6 and that this Pax family member has a direct role in the continuing expression of tissue-specific genes.
C1 NEI,MOLEC & DEV BIOL LAB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892.
   NEI,MOLEC & DEV BIOL LAB,MOLEC GENET SECT,BETHESDA,MD 20892.
RI Cvekl, Ales/B-2427-2013
NR 35
TC 110
Z9 110
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4676
EP 4680
DI 10.1073/pnas.92.10.4676
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600120
PM 7753863
ER

PT J
AU CVEKL, A
   SAX, CM
   LI, X
   MCDERMOTT, JB
   PIATIGORSKY, J
AF CVEKL, A
   SAX, CM
   LI, X
   MCDERMOTT, JB
   PIATIGORSKY, J
TI PAX-6 AND LENS-SPECIFIC TRANSCRIPTION OF THE CHICKEN DELTA-1-CRYSTALLIN
   GENE
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID DELTA-CRYSTALLIN GENES; HOMEOBOX-CONTAINING GENE; ARGININOSUCCINATE
   LYASE; TRANSGENIC MICE; NONLENS TISSUES; MESSENGER-RNA; BINDING-SITE;
   EXPRESSION; PROTEINS; ENHANCER
AB The abundance of S-crystallin in the chicken eye lens provides an advantageous marker for tissue-specific gene expression during cellular differentiation. The lens-specific expression of the delta 1-crystallin gene is governed by an enhancer in the third intron, which binds a positive (delta EF2) and negative (delta EF1) factor in its core region. Here we show by DNase I footprinting, electrophoretic mobility-shift assays, and cotransfection experiments with the delta 1-promoter/enhancer fused to the chloramphenicol acetyltransferase reporter gene that the delta 1-crystallin enhancer has two adjacent functional Pax-6 binding sites. We also demonstrate by DNase I footprinting that the delta EF1 site can bind the transcription factor USF, raising the possibility that USF may cooperate with Pax-6 in activation of the chicken delta 1- and alpha A-crystallin genes, These data, coupled with our recent demonstration that Pax-6 activates the alpha A-crystallin gene, suggest that Pax-6 may have been used extensively throughout evolution to recruit and express crystallin genes in the lens.
C1 NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA.
RI Cvekl, Ales/B-2427-2013
NR 58
TC 85
Z9 87
U1 0
U2 2
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 MAY 9
PY 1995
VL 92
IS 10
BP 4681
EP 4685
DI 10.1073/pnas.92.10.4681
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600121
PM 7753864
ER

PT J
AU PERANTONI, AO
   DOVE, LF
   KARAVANOVA, I
AF PERANTONI, AO
   DOVE, LF
   KARAVANOVA, I
TI BASIC FIBROBLAST GROWTH-FACTOR CAN MEDIATE THE EARLY INDUCTIVE EVENTS IN
   RENAL DEVELOPMENT
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE FGF2; C-MET; KIDNEY; WT1
ID EMBRYONIC KIDNEY; METANEPHROGENIC MESENCHYME; BOVINE KIDNEY;
   CELL-SURFACE; HEPARIN; EXPRESSION; RECEPTOR; BINDING; APOPTOSIS;
   SYNDECAN
AB The earliest characterized events during induction of tubulogenesis in renal anlage include the condensation or compaction of metanephrogenic mesenchyme with the concurrent upregulation of WT1, the gene encoding the Wilms tumor transcriptional activator/suppressor. We report that basic fibroblast growth factor (FGF2) can mimic the early effects of an inductor tissue by promoting the condensation of mesenchyme and inhibiting the tissue degeneration associated with the absence of an inductor tissue. By in situ hybridization, FGF2 was also found to mediate the transcriptional activation of WT1 and of the hepatocyte growth factor receptor gene, c-met. Although FGF2 can induce these early events of renal tubulogenesis, it cannot promote the epithelial conversion associated with tubule formation in metanephrogenic mesenchyme. For this, an undefined factor(s) from pituitary extract in combination with FGF2 can cause tubule formation in uninduced mesenchyme. These findings support the concept that induction in kidney is a multiphasic process that is mediated by more than a single comprehensive inductive factor and that soluble molecules can mimic these inductive activities in isolated uninduced metanephrogenic mesenchyme.
RP PERANTONI, AO (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA.
NR 44
TC 136
Z9 137
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 MAY 9
PY 1995
VL 92
IS 10
BP 4696
EP 4700
DI 10.1073/pnas.92.10.4696
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600124
PM 7753867
ER

PT J
AU KWAN, SP
   HAGEMANN, TL
   RADTKE, BE
   BLAESE, RM
   ROSEN, FS
AF KWAN, SP
   HAGEMANN, TL
   RADTKE, BE
   BLAESE, RM
   ROSEN, FS
TI IDENTIFICATION OF MUTATIONS IN THE WISKOTT-ALDRICH SYNDROME GENE AND
   CHARACTERIZATION OF A POLYMORPHIC DINUCLEOTIDE REPEAT AT DXS6940,
   ADJACENT TO THE DISEASE GENE
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID RNA SPLICE JUNCTIONS; HUMAN X-CHROMOSOME; HUMAN DNA; LOCALIZATION;
   SEQUENCES; CARRIER; LYMPHOCYTES; LIBRARIES; LINKAGE; MARKERS
AB The Wiskott-Aldrich syndrome (WAS) is an X-chromosome-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The disease gene has been localized to the proximal short arm of the X chromosome and recently isolated through positional cloning. The function of the encoded protein remains undetermined. In this study we have characterized mutations in 12 unrelated patients to confirm the identity of the disease gene. We have also revised the coding sequence and genomic structure for the WAS gene. To analyze further the transmittance of the disease gene, we have characterized a polymorphic microsatellite at the DXS6940 locus within 30 kb of the gene and demonstrate the inheritance of the affected alleles in families with a history of WAS.
C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892.
   HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115.
RP KWAN, SP (reprint author), RUSH UNIV,SCH MED,DEPT IMMUNOL,CHICAGO,IL 60612, USA.
FU NCRR NIH HHS [RR02172]; NIAID NIH HHS [AI31587, AI31541]
NR 35
TC 92
Z9 96
U1 1
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 9
PY 1995
VL 92
IS 10
BP 4706
EP 4710
DI 10.1073/pnas.92.10.4706
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QX876
UT WOS:A1995QX87600126
PM 7753869
ER

PT J
AU DOLIN, R
   AMATO, DA
   FISCHL, MA
   PETTINELLI, C
   BELTANGADY, M
   LIOU, SH
   BROWN, MJ
   CROSS, AP
   HIRSCH, MS
   HARDY, WD
   MILDVAN, D
   BLAIR, DC
   POWDERLY, WG
   PARA, MF
   FIFE, KH
   STEIGBIGEL, RT
   SMALDONE, L
   CRUMPACKER, CS
   COOLEY, T
   MITSUYASO, RT
   JOHN, R
   SANDERS, C
   REITMAN, D
   HEWITT, R
   REICHMAN, RC
   GELB, LD
   MCGUIRE, ML
   JONES, M
   NEIDIG, JL
   ZWICKL, B
   HARTMAN, PB
   ROARKE, ME
   BURK, RA
   FUHRER, J
   SOMOGYI, KA
   SEPKOWITZ, K
   TELZAK, EE
   MCAULIFFE, VJ
   VALENTINE, FT
   VASQUEZ, M
   MERIGAN, TC
   KATZENSTEIN, D
   FESSELL, J
   HAVLIR, DV
   RICHMAN, DD
   SPECTOR, SA
   KAHN, JO
   JOHNSON, L
   COLEMAN, R
   HO, M
   MCMAHON, D
   PAZIN, G
   ANTONISKIS, D
   MCNAMARA, B
   DIAMOND, D
   COLLIER, AC
   PARADISE, MA
   WALD, A
   DEPAOLISJONES, A
   HENRY, K
   WASKIN, HA
   HYSLOP, NE
   MUSHATT, DM
   ZACHARY, JA
   SOEIRO, R
   HARRIS, C
   ZINGMAN, B
   GIORDANO, MF
   SLEDZ, S
   MURRAY, HW
   CAREY, JT
   DAVIS, TL
   BAGBY, B
   KESSLER, HA
   MURPHY, RL
   HIRSCHTICK, RE
   CHEESEMAN, SH
   LAI, KK
   FAIRCHILD, PG
   EHMANN, WC
   ZURLO, JJ
   MILLARD, R
   TROIANI, L
   HEGGEN, AA
   VANDERHORST, CM
   MCKINLEY, GF
   GRIECO, MH
   KOLATCH, BR
   GOLDSMITH, JC
   GOMPERTS, ED
   WOODS, LM
   GRUE, L
   MAYJO, K
   BECKER, RL
   JAYAWEERA, DT
   ROLFE, L
   COLE, J
   JERMANO, J
AF DOLIN, R
   AMATO, DA
   FISCHL, MA
   PETTINELLI, C
   BELTANGADY, M
   LIOU, SH
   BROWN, MJ
   CROSS, AP
   HIRSCH, MS
   HARDY, WD
   MILDVAN, D
   BLAIR, DC
   POWDERLY, WG
   PARA, MF
   FIFE, KH
   STEIGBIGEL, RT
   SMALDONE, L
   CRUMPACKER, CS
   COOLEY, T
   MITSUYASO, RT
   JOHN, R
   SANDERS, C
   REITMAN, D
   HEWITT, R
   REICHMAN, RC
   GELB, LD
   MCGUIRE, ML
   JONES, M
   NEIDIG, JL
   ZWICKL, B
   HARTMAN, PB
   ROARKE, ME
   BURK, RA
   FUHRER, J
   SOMOGYI, KA
   SEPKOWITZ, K
   TELZAK, EE
   MCAULIFFE, VJ
   VALENTINE, FT
   VASQUEZ, M
   MERIGAN, TC
   KATZENSTEIN, D
   FESSELL, J
   HAVLIR, DV
   RICHMAN, DD
   SPECTOR, SA
   KAHN, JO
   JOHNSON, L
   COLEMAN, R
   HO, M
   MCMAHON, D
   PAZIN, G
   ANTONISKIS, D
   MCNAMARA, B
   DIAMOND, D
   COLLIER, AC
   PARADISE, MA
   WALD, A
   DEPAOLISJONES, A
   HENRY, K
   WASKIN, HA
   HYSLOP, NE
   MUSHATT, DM
   ZACHARY, JA
   SOEIRO, R
   HARRIS, C
   ZINGMAN, B
   GIORDANO, MF
   SLEDZ, S
   MURRAY, HW
   CAREY, JT
   DAVIS, TL
   BAGBY, B
   KESSLER, HA
   MURPHY, RL
   HIRSCHTICK, RE
   CHEESEMAN, SH
   LAI, KK
   FAIRCHILD, PG
   EHMANN, WC
   ZURLO, JJ
   MILLARD, R
   TROIANI, L
   HEGGEN, AA
   VANDERHORST, CM
   MCKINLEY, GF
   GRIECO, MH
   KOLATCH, BR
   GOLDSMITH, JC
   GOMPERTS, ED
   WOODS, LM
   GRUE, L
   MAYJO, K
   BECKER, RL
   JAYAWEERA, DT
   ROLFE, L
   COLE, J
   JERMANO, J
TI ZIDOVUDINE COMPARED WITH DIDANOSINE IN PATIENTS WITH ADVANCED HIV TYPE-1
   INFECTION AND LITTLE OR NO PREVIOUS EXPERIENCE WITH ZIDOVUDINE
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED
   TRIAL; PHASE-I TRIAL; DOUBLE-BLIND; 2',3'-DIDEOXYINOSINE DDI;
   AZIDOTHYMIDINE AZT; TOXICITY; DISEASE; EFFICACY
AB Background: We conducted a trial to compare treatment with zidovudine or didanosine in patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had received little or no previous therapy with zidovudine.
   Methods: Six hundred seventeen patients with acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex (CD4 cell count, less than or equal to 0.03x10(9)/L [300/mu L]), or asymptomatic HIV (CD4 cell count, less than or equal to 0.20x10(9)/L) received zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a randomized, double-blind allocation, with cross-over to alternative medication after development of an end point or serious toxic effect. To be eligible, patients must have received either no or up to 16 weeks of zidovudine therapy before entry into the study. Primary end points were development of a new AIDS-defining event or death. Secondary clinical end points were new or recurrent AIDS-defining events, or death, and survival.
   Results: In the study as a whole, there were no differences in the relative risks (RRs) of the development of end points between treatment groups. However, there was a strong interaction between the relative efficacies of zidovudine and didanosine and previous experience with zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine was more effective than 750 mg/d of didanosine (RR, 1.43; 90% confidence interval [CI], 1.02 to 2.00), with a similar trend for zidovudine compared with 500 mg/d of didanosine (RR, 1.21;90% CI, 0.86 to 1.71). However, among 118 patients with more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500 mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to 0.86); there was a similar trend for increased effectiveness of 750 mg/d of didanosine compared with zidovudine (RR, 0.61;90% CI, 0.36 to 1.03). Among 119 patients who had some but no more than 8 weeks of previous zidovudine therapy, there were no significant differences among the treatment arms. Similar findings were noted in the analysis of the two secondary clinical end points. No significant differences were found in efficacy between the groups receiving 500 and 750 mg/d of didanosine. The major toxic effect associated with zidovudine was hematopoietic (granulocytopenia) and that associated with didanosine was pancreatitis (dosage, 750 mg/d).
   Conclusions: In patients with advanced HIV disease, zidovudine appears to be more effective than didanosine as initial therapy; however, some patients with advanced HIV disease may benefit from a change to didanosine therapy after as little as 8 to 16 weeks of therapy with zidovudine.
C1 UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642.
   HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115.
   UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL.
   NIAID,DIV AIDS,BETHESDA,MD 20892.
   BRISTOL MYERS SQUIBB PHARMACEUT RES INST,WALLINGFORD,CT.
   HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA.
   UNIV CALIF LOS ANGELES,CTR CARE,DEPT MED,LOS ANGELES,CA.
   BETH ISRAEL MED CTR,DIV INFECT DIS,NEW YORK,NY 10003.
   SUNY SYRACUSE,DEPT MED,SYRACUSE,NY.
   UNIV WASHINGTON,DIV INFECT DIS,ST LOUIS,MO.
   OHIO STATE UNIV,COLL MED,DEPT INTERNAL MED,COLUMBUS,OH 43210.
   INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN.
   SUNY STONY BROOK,DIV INFECT DIS,STONY BROOK,NY 11794.
RI Wald, Anna/B-6272-2012
OI Wald, Anna/0000-0003-3486-6438
NR 30
TC 56
Z9 56
U1 1
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 MAY 8
PY 1995
VL 155
IS 9
BP 961
EP 974
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW172
UT WOS:A1995QW17200010
PM 7726705
ER

PT J
AU YURDAYDIN, C
   WALSH, TJ
   ENGLER, HD
   HA, JH
   LI, Y
   JONES, EA
   BASILE, AS
AF YURDAYDIN, C
   WALSH, TJ
   ENGLER, HD
   HA, JH
   LI, Y
   JONES, EA
   BASILE, AS
TI GUT BACTERIA PROVIDE PRECURSORS OF BENZODIAZEPINE RECEPTOR LIGANDS IN A
   RAT MODEL OF HEPATIC-ENCEPHALOPATHY
SO BRAIN RESEARCH
LA English
DT Article
DE BENZODIAZEPINE RECEPTOR; HEPATIC ENCEPHALOPATHY; ANTIBIOTIC;
   ACINETOBACTER; RAT; BRAIN
ID ACINETOBACTER-CALCOACETICUS; RABBIT MODEL; PATHOGENESIS; FLUMAZENIL;
   RELEASE; COMPLEX; FAILURE
AB Benzodiazepine receptor (BZR) ligands are elevated in animals and humans with fulminant hepatic failure (FHF) and contribute to the pathogenesis of the associated hepatic encephalopathy (HE). As gut factors are proposed to play a role in the pathogenesis of HE, we investigated gut flora as a source of BZR ligands. Rats received daily oral neomycin, vancomycin and metronidazole (AB +) or saline (AB -) before and concurrent with the induction of FHF with thioacetamide. BZR ligands were extracted from brain and plasma and quantified using radiometric techniques. Plasma BZR ligand concentrations in AB(+) and AB(-) rats with HE were higher than AB(+) and AB(-) control rats. Brain BZR ligand concentrations increased in AB(+) and AB(-) rats with HE. Stool cultures from antibiotic treated rats with HE indicated the presence of multidrug resistant Acinetobacter lwoffii. Although no significant concentrations of BZR ligands were detected in culture media inoculated with A. lwoffii, administering A. lwoffii to normal rats significantly elevated BZR ligand levels in brain, but not plasma. Thus, antibiotic treatment of rats is associated with the growth of a resistant strain of bacterium which produces an inactive BZR ligand precursor. BZR ligands may be synthesized from these precursors in the brain and efficiently cleared by a normal liver following brain-to-plasma transfer. Impairment of this clearance process in FHF facilitates their accumulation, enabling agonist BZR ligands to contribute to the pathogenesis of HE by further enhancing GABAergic neurotransmission.
C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892.
   NIDDK,LIVER DIS SECT,BETHESDA,MD 20892.
   NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD.
   CTR CLIN,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD.
NR 27
TC 46
Z9 48
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 MAY 8
PY 1995
VL 679
IS 1
BP 42
EP 48
DI 10.1016/0006-8993(95)00241-H
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA QY395
UT WOS:A1995QY39500006
PM 7648264
ER

PT J
AU WAKABAYASHI, S
   FREED, LM
   CHANG, M
   RAPOPORT, SI
AF WAKABAYASHI, S
   FREED, LM
   CHANG, M
   RAPOPORT, SI
TI IN-VIVO IMAGING OF BRAIN INCORPORATION OF FATTY-ACIDS AND OF
   2-DEOXY-D-GLUCOSE DEMONSTRATES FUNCTIONAL AND STRUCTURAL NEUROPLASTIC
   EFFECTS OF CHRONIC UNILATERAL VISUAL DEPRIVATION IN RATS
SO BRAIN RESEARCH
LA English
DT Article
DE BRAIN; ARACHIDONATE; DOCOSAHEXAENOATE; PALMITATE; DEOXYGLUCOSE;
   QUANTITATIVE AUTORADIOGRAPHY; VISUAL SYSTEM; ORBITAL ENUCLEATION; RAT;
   FATTY ACID; LIPID; PHOSPHOLIPID; GLUCOSE; VISION; NEUROPLASTICITY;
   FUNCTIONAL ACTIVITY
ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL PALMITATE INCORPORATION; PLASMA C-14
   PALMITATE; CHOLINERGIC STIMULATION; UNANESTHETIZED RATS;
   GLUCOSE-UTILIZATION; ORBITAL ENUCLEATION; METABOLIC-ACTIVITY;
   ARACHIDONIC-ACID; EYE REMOVAL
AB Regional cerebral 'incorporation coefficients' k * of each of 3 labeled long-chain fatty acids - [9,10-H-3]palmitate ([H-3]PA), [1-C-14]arachidonate ([C-14]AA) and [1-C-14]docosahexaenoate ([C-14]DHA) - were measured using quantitative autoradiography in 11 bilateral brain visual areas of 3.5-month-old awake, hooded, Long-Evans rats, and were compared with regional cerebral metabolic rates for glucose (rCMR(glc)). The rats, which had undergone unilateral orbital enucleation at 15 days of age, were studied either in the dark with eyelids of the intact eye sutured, or when stimulated in a light box with the intact eye open. rCMR(glc) did not differ between homologous contralateral and ipsilateral visual areas in the dark or during stimulation, but was elevated bilaterally by 25% or more in many visual areas during stimulation compared with dark. Contralateral compared with ipsilateral k * was lower for each fatty acid tracer in superficial gray of the superior colliculus (in dark and during stimulation) and dorsal nucleus of lateral geniculate body (during stimulation). In the dark, k * for [H-3]PA was correlated significantly with rCMR(glc) for the 22 visual areas studied, whereas during stimulation k * for [C-14]AA was correlated with rCMR(glc). These results suggest that central neuroplastic changes following chronic unilateral enucleation are accompanied by reduced incorporation of [H-3]PA, [C-14]AA and [C-14]DHA into contralateral brain areas that normally receive crossed retinofugal fibers, and by symmetry of rCMR(glc) in the dark but increased bilateral symmetrical responsiveness of rCMR(glc) to visual stimulation of the intact eye.
C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892.
NR 66
TC 14
Z9 14
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 MAY 8
PY 1995
VL 679
IS 1
BP 110
EP 122
DI 10.1016/0006-8993(95)00069-3
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA QY395
UT WOS:A1995QY39500013
PM 7648253
ER

PT J
AU CORCORAN, ML
   KIBBEY, MC
   KLEINMAN, HK
   WAHL, LM
AF CORCORAN, ML
   KIBBEY, MC
   KLEINMAN, HK
   WAHL, LM
TI LAMININ SIKVAV PEPTIDE INDUCTION OF MONOCYTE-MACROPHAGE PROSTAGLANDIN
   E(2) AND MATRIX METALLOPROTEINASES
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Note
ID IV COLLAGENASE; BASEMENT-MEMBRANE; TUMOR-GROWTH; A-CHAIN; INHIBITION;
   ACTIVATION; RECEPTOR; INVIVO; CELLS
AB The laminin-derived synthetic peptide containing the SIKVAV (Ser-Ile-Lys-Val-Ala-Val) amino acid sequence has been previously shown to regulate tumor invasion, metastasis, and angiogenesis. Here, we demonstate that this peptide also modulates human monocyte responses. Moreover, the monocytic responses elicited by this peptide are influenced by the culture conditions. When elutriated monocytes were cultured on SIKVAV substrate or in suspension with this peptide, the synthesis of prostaglandin E(2), interstitial collagenase, and gelatinase B was induced and was further enhanced in the presence of concanavalin A (ConA). However, when monocytes were adhered before adding soluble SIKVAV, the peptide alone failed to induce the production of prostaglandin E(2) or matrix metalloproteinases. If adherent monocytes were exposed to SIKVAV in the presence of ConA, this peptide enhanced the ConA induced production of these mediators. In contrast to SIKVAV, the intact laminin molecule failed to influence these monocyte responses. This is the first demonstration that a laminin derived peptide is capable of inducing or enhancing monocyte inflammatory responses that may influence a number of biological activities such as wound healing or excessive connective tissue destruction associated with chronic inflammation.
C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892.
   NIDR,DEV BIOL LAB,CELL BIOL SECT,BETHESDA,MD 20892.
NR 24
TC 51
Z9 51
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 5
PY 1995
VL 270
IS 18
BP 10365
EP 10368
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100002
PM 7737965
ER

PT J
AU MARKS, MS
   GERMAIN, RN
   BONIFACINO, JS
AF MARKS, MS
   GERMAIN, RN
   BONIFACINO, JS
TI TRANSIENT AGGREGATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II
   CHAINS DURING ASSEMBLY IN NORMAL SPLEEN-CELLS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HLA-DR MOLECULES; INVARIANT CHAIN; ENDOPLASMIC-RETICULUM;
   INTRACELLULAR-TRANSPORT; BINDING-PROTEIN; PEPTIDE BINDING; MICE LACKING;
   ASSOCIATION; EXPRESSION; ANTIGENS
AB Many cell surface proteins exist as complexes of multiple subunits. It is well established that most such complexes are assembled within the endoplasmic reticulum (ER). However, the mechanistic details of the assembly process are largely unknown. We show here that alpha and beta subunits of major histocompatibility complex class II antigens in spleen cells of normal mice pass through a transiently aggregated phase in the ER prior to assembly with the invariant chain (Ii). Aggregates form immediately after synthesis and disappear concomitantly with assembly of mature alpha beta Ii complexes. In spleen cells lacking Ii, aggregates fail to be efficiently dissociated over time, implicating subunit assembly as a requirement for disaggregation. Two ER chaperones, BiP and calnexin, bind to newly synthesized class II MHC chains but do not contribute appreciably to the large size of the aggregates. Our observations suggest that some subunits of multisubunit complexes pass through a transient, dynamic high molecular weight aggregate phase during the physiological process of assembly. The results further suggest a novel role for Ii in promoting stable dissociation of preformed aggregates containing alpha and beta subunits rather than in preventing their formation.
C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892.
   NIAID,IMMUNOL LAB,BETHESDA,MD 20892.
OI Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan
   S./0000-0002-5673-6370
NR 51
TC 39
Z9 40
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 MAY 5
PY 1995
VL 270
IS 18
BP 10475
EP 10481
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100020
PM 7737982
ER

PT J
AU SHEARS, SB
   ALI, N
   CRAXTON, A
   BEMBENEK, ME
AF SHEARS, SB
   ALI, N
   CRAXTON, A
   BEMBENEK, ME
TI SYNTHESIS AND METABOLISM OF BIS-DIPHOSPHOINOSITOL TETRAKISPHOSPHATE
   IN-VITRO AND IN-VIVO
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELLS; 3-PHOSPHATASE; PURIFICATION; TURNOVER
AB The pathway of synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate (PP-InsP(4)-PP) was elucidated by high performance liquid chromatography using newly available H-3- and P-32-labeled substrates. Metabolites were also identified by using two purified phosphatases in a structurally diagnostic manner: tobacco ''pyrophosphatase'' (Shinshi, Ii,, Miwa, M., Kato, K., Noguchi, M. Matsushima, T., and Sugimura, T. (1976) Biochemistry 15, 2185-2190) and rat hepatic multiple inositol polyphosphate phosphatase (MIPP; Craxton, A., All, N., and Shears, S. B. (1995) Biochem. J. 305, 491-498). The demonstration that diphosphoinositol polyphosphates were hydrolyzed by MIPP provides new information on its substrate specificity, although MIPP did not metabolize significant amounts of these polyphosphates in either rat liver homogenates or intact AR4-2J cells. In liver homogenates, inositol hexakisphosphate (InsP(6)) was phosphorylated first to a diphosphoinositol pentakisphosphate (PP-InsP(5)) and then to PP-InsP(4)-PP. These kinase reactions were reversed by phosphatases, establishing two coupled substrate cycles. The two dephosphorylations were probably performed by distinct phosphatases that were distinguished by their separate positional specificities, and their different sensitivities to inhibition by F- (IC50 values of 0.03 mM and 1.4 mM against PP-InsP(5) and PP-InsP(5)-PP, respectively). In [H-3]inositol-labeled AR4-2J cells, the steady-state levels of PP-[H-3]InsP(5) and PP-[H-3]InsP(4)-PP were, respectively, 2-3 and 0.6% of the level of [H-3]InsP(6). The ongoing turnover of these polyphosphates was revealed by treatment of cells with 0.8 mM NaF for 40 min, which reduced levels of [H-3]InsP(6) by 50%, increased the levels of PP-[H-3]InsP(5) 16-fold, and increased levels of PP-[H-3]InsP(4)-PP 5-fold. A large increase in levels of PP-[H-3]InsP(5) also occurred in cells treated with 10 mM NaF, but then no significant change to levels of PP-[H-3]InsP(4)-PP were observed; there may be important differences in the control of the turnover of these two compounds.
C1 DUPONT CO INC,DEPT MED PROD,NEN,BOSTON,MA 02118.
RP SHEARS, SB (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709, USA.
NR 19
TC 54
Z9 57
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 MAY 5
PY 1995
VL 270
IS 18
BP 10489
EP 10497
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100022
PM 7737983
ER

PT J
AU CHU, SC
   WU, HP
   BANKS, TC
   EISSA, NT
   MOSS, J
AF CHU, SC
   WU, HP
   BANKS, TC
   EISSA, NT
   MOSS, J
TI STRUCTURAL DIVERSITY IN THE 5'-UNTRANSLATED REGION OF
   CYTOKINE-STIMULATED HUMAN INDUCIBLE NITRIC-OXIDE SYNTHASE MESSENGER-RNA
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CONDUCTANCE REGULATOR GENE; MESSENGER-RNA TRANSCRIPTS; 5' UNTRANSLATED
   REGION; TRANSLATIONAL CONTROL; CYSTIC-FIBROSIS; CODING SEQUENCES;
   EXPRESSION; MODEL; GCN4; INDIVIDUALS
AB Inducible nitric oxide synthase, the critical enzyme responsible for the enhanced synthesis of nitric oxide in inflammatory states, is widely expressed in mammalian cells. To evaluate potential regulatory roles of the 5'-untranslated region (UTR) in the human inducible nitric oxide synthase gene, the transcription initiation sites and structure of the 5'-UTR of human inducible nitric oxide synthase were examined. Freshly isolated human alveolar macrophages, bronchial epithelial cells, and several types of cultured cells were evaluated following stimulation with cytokines (i.e. interferon-gamma, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6). The mRNA was analyzed by reverse transcription-polymerase chain reaction, Northern analysis, and 5'-rapid amplification of cDNA ends. Despite the presence of a TATA box in the promoter region, multiple transcription initiation sites were observed, some extending several hundred base pairs upstream from the main TATA-directed initiation site. Alternative splicing in the 5'-UTR of human inducible nitric oxide synthase mRNA resulted in further diversity. The TATA-independent inducible nitric oxide synthase mRNA transcripts were up-regulated by cytokines. The long and complex 5'-UTRs contain eight partially overlapping open reading frames upstream of the putative inducible nitric oxide synthase ATG, which may have an important role in translational regulation of human inducible nitric oxide synthase mRNA.
RP CHU, SC (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,BLDG 10,RM 6D03,10 CTR DR MSC 1590,BETHESDA,MD 20892, USA.
NR 39
TC 61
Z9 62
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 MAY 5
PY 1995
VL 270
IS 18
BP 10625
EP 10630
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100042
PM 7537735
ER

PT J
AU SAITOH, H
   DASSO, M
AF SAITOH, H
   DASSO, M
TI THE RCC1 PROTEIN INTERACTS WITH RAN, RANBP1, HSC70, AND A 340-KDA
   PROTEIN IN XENOPUS EXTRACTS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA-REPLICATION; CHROMOSOME CONDENSATION; KARYOPHILIC PROTEINS;
   CELL-CYCLE; REGULATOR; CLEAVAGE; NUCLEUS; MITOSIS
AB RCC1 is an abundant, highly conserved, chromatin-associated protein whose function is necessary for the preservation of a properly ordered cell cycle, RCC1 is also necessary for numerous nuclear processes, including nuclear transport and RNA metabolism; and it functions enzymatically as a guanine nucleotide exchange factor for a small, ras related GTPase called Ran. Studies in several organisms suggest that RCC1 may be part of a large complex containing multiple proteins. There is also evidence that RCC1 associates with chromatin through other proteins and that the binding of the complex to chromatin varies within the cell cycle. In order to characterize this putative complex, we have identified a number of other proteins as candidate compo nents of the complex by their association with a GST-RCC1 fusion protein. Three of these proteins have previously been identified (Ran, RanBP1, and hsc70). The fourth protein is novel and has a molecular mass of 340 kDa. In this report, we discuss a preliminary characterization of the interactions between these proteins.
C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892.
OI Dasso, Mary/0000-0002-5410-1371
NR 26
TC 27
Z9 28
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 MAY 5
PY 1995
VL 270
IS 18
BP 10658
EP 10663
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100046
PM 7738003
ER

PT J
AU KAZANIETZ, MG
   LEWIN, NE
   BRUNS, JD
   BLUMBERG, PM
AF KAZANIETZ, MG
   LEWIN, NE
   BRUNS, JD
   BLUMBERG, PM
TI CHARACTERIZATION OF THE CYSTEINE-RICH REGION OF THE
   CAENORHABDITIS-ELEGANS PROTEIN UNC-13 AS A HIGH-AFFINITY PHORBOL ESTER
   RECEPTOR - ANALYSIS OF LIGAND-BINDING INTERACTIONS, LIPID COFACTOR
   REQUIREMENTS, AND INHIBITOR SENSITIVITY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; KINASE-C ISOZYMES; REGULATORY DOMAIN;
   MOUSE-BRAIN; GENE; CALCIUM; DIACYLGLYCEROL; EXPRESSION; CHIMAERIN;
   CYTOSOL
AB The Caenorhabditis elegans Unc-13 protein is a novel member of the phorbol ester receptor family having a single cysteine-rich region with high homology to those present in protein kinase C (PKC) isozymes and the chimaerins, We expressed the cysteine-rich region of Unc-13 in Escherichia coli and quantitatively analyzed its interactions with phorbol esters and related analogs, its phospholipid requirements, and its inhibitor sensitivity, [H-3]Phorbol 12,13-dibutyrate [H-3]PDBu bound with high affinity to the cysteine-rich region of Unc-13 (K-d = 1.3 +/- 0.2 nM). This affinity is similar to that of other single cysteine-rich regions from PKC isozymes as well as n-chimaerin, As also described for PKC isozymes and n-chimaerin, Unc-13 bound diacylglycerol with an affinity about 2 orders of magnitude weaker than [H-3]PDBu. Structure activity analysis revealed significant but modest differences between recombinant cysteine-rich regions of Unc-13 and PKC delta. In addition, Unc-13 required slightly higher concentrations of phospholipid for reconstitution of [H-3]PDBu binding. Calphostin C, a compound described as a selective inhibitor of PKC, was also able to inhibit [H-3]PDBu binding to Unc-13, suggesting that this inhibitor is not able to distinguish between different classes of phorbol ester receptors, In conclusion, although our results revealed some differences in ligand and lipid cofactor sensitivities, Unc-13 represents a high affinity cellular target for the phorbol esters as well as for the lipid second messenger diacylglycerol, at least in C. elegans, The use of phorbol esters or some ''specific'' antagonists of PKC does not distinguish between cellular pathways involving different PKC isozymes or novel phorbol ester receptors such as n-chimaerin or Unc-13.
C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892.
NR 37
TC 76
Z9 79
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 MAY 5
PY 1995
VL 270
IS 18
BP 10777
EP 10783
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100061
PM 7537738
ER

PT J
AU HIRASAWA, N
   SCHARENBERG, A
   YAMAMURA, H
   BEAVEN, MA
   KINET, JP
AF HIRASAWA, N
   SCHARENBERG, A
   YAMAMURA, H
   BEAVEN, MA
   KINET, JP
TI A REQUIREMENT FOR SYK IN THE ACTIVATION OF THE MICROTUBULE-ASSOCIATED
   PROTEIN-KINASE PHOSPHOLIPASE-A(2) PATHWAY BY FC-EPSILON-R1 IS NOT SHARED
   BY A G-PROTEIN-COUPLED RECEPTOR
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BASOPHILIC LEUKEMIA-CELLS; TUMOR MAST-CELLS; TYROSINE PHOSPHORYLATION;
   RBL-2H3 CELLS; ANTIGEN RECEPTOR; HIGH-AFFINITY; SIGNAL TRANSDUCTION;
   HISTAMINE-RELEASE; IMMUNOGLOBULIN-E; 2H3 CELLS
AB Stimulation of the mast cell line, RBL-2H3, with antigen via the tetrameric (alpha beta gamma(2)) immunoglobulin E receptor (Fc epsilon R1) leads to the activation of cytosolic phospholipase A(2) and the release of arachidonic acid. This pathway is dependent on the activation of the mitogen-activated protein (MAP) kinase, In this paper, we show that the MAP kinase/cytosolic phospholipase A(2) pathway is linked to Fc epsilon R1 via the cytosolic tyrosine kinase, Syk, and that the GDP/GTP exchange factor, Vav, might be one candidate for accomplishing this link, Cross-linking of transmembrane chimeras containing the Fc epsilon R1 gamma motif, which is known to activate Syk, results in the tyrosine phosphorylation of Vav, activation of MAP kinase, and release of arachidonic acid. Cross-linking of chimeras containing the Fc epsilon R1 beta motif does not cause these events, Furthermore, stimulation of these events by antigen is enhanced by transient overexpression of a wild-type form of Syk and blocked by overexpression of a dominant negative form of Syk, By contrast, stimulation via the transfected, G protein-coupled, muscarinic mi receptor is not influenced by either form of Syk and does not result in tyrosine phosphorylation of Vav, These data establish unequivocally that the two types of receptor are independently linked to the MAP kinase/ cytosolic phospholipase A(2) pathway and demonstrate the existence of the Fc epsilon R1-Syk-MAP kinase pathway.
C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892.
   NIAID,MOLEC ALLERGY & IMMUNOL SECT,BETHESDA,MD 20892.
   FUKUI MED SCH,DEPT BIOCHEM,FUKUI 91011,JAPAN.
NR 50
TC 141
Z9 141
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 MAY 5
PY 1995
VL 270
IS 18
BP 10960
EP 10967
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW601
UT WOS:A1995QW60100086
PM 7537741
ER

PT J
AU PARTILLA, JS
   YOU, J
   ROTHMAN, RB
AF PARTILLA, JS
   YOU, J
   ROTHMAN, RB
TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC RESOLUTION OF SYNTHETIC OPIATE
   AND ANTI-OPIATE PEPTIDES FROM HUMAN PLASMA
SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS
LA English
DT Article
ID BETA-ENDORPHIN; RAT; NEUROPEPTIDES; DYNORPHIN
AB An assay system using reversed-phase high-performance liquid chromatographic (HPLC) resolution of synthetic anti-opioid peptides (AOPs) and opioid peptides (OPs) was developed. Samples were diluted with trifluoroacetic acid, loaded onto Sep-Pak C-18 cartridges, eluted, dried, and redissolved in ethanol-acetic acid-water. Retention-time consistency was established, and high levels of synthetic AOP and OP recovery, generally higher than 80%, were achieved. In a single HPLC run synthetic enkephalins, dynorphins, and beta-endorphins were separated even when extracted from human plasma using a volatile mobile phase which yielded fractions totally compatible with quantitation by radioimmunossay. Combining the resolution of HPLC with the sensitivity of radioimmunoassay (RIA) may facilitate simultaneous measurement of numerous neuropeptides in body fluids such as plasma and cerebrospinal fluid.
C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224.
NR 9
TC 5
Z9 6
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 MAY 5
PY 1995
VL 667
IS 1
BP 49
EP 56
DI 10.1016/0378-4347(94)00594-U
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA QY358
UT WOS:A1995QY35800003
PM 7663685
ER

PT J
AU TSAI, YF
   CHEN, TJ
   PI, WP
   TAI, MY
   HUANG, RL
   CHIUEH, CC
   PENG, MT
AF TSAI, YF
   CHEN, TJ
   PI, WP
   TAI, MY
   HUANG, RL
   CHIUEH, CC
   PENG, MT
TI EFFECTS OF FETAL BRAIN GRAFTING ON ADULT BEHAVIORAL MASCULINIZATION AND
   DEFEMINIZATION IN NEONATALLY ANDROGENIZED FEMALE RATS
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE MOUNT; LORDOSIS; FETAL BRAIN GRAFTING; ANDROGEN-STERILIZED RAT; PREOPTIC
   AREA; VENTROMEDIAL HYPOTHALAMUS
ID MEDIAL PREOPTIC AREA; SEXUAL-BEHAVIOR; MOUNTING BEHAVIOR; INDUCE
   RECOVERY; LESIONED RATS; AGED RATS; IMPAIRMENTS; RESTORATION
AB Treatment of neonatal female rats with androgen results not only in decreased female sexual behavior but also in enhanced male sexual behavior examined in adulthood. The effects of grafting fetal preoptic area (POA) neurons into the POA, and fetal hypothalamic (HPT) neurons into the ventromedial hypothalamus (VMH), were tested in neonatally androgen-sterilized rats (ASR). The rats were injected subcutaneously with 80 mu g testosterone propionate within the 24 hours after birth to see if sexual behavior could be normalized by fetal brain grafts. In repeated tests on ASR grafted with fetal HPT into the VMH, the lordotic response was seen to increase to the level seen in non-ASR controls, while the increase in mounting behavior in ASR was suppressed following grafting of fetal POA or cerebral cortex into the POA. These results suggest that there are dysfunctions of POA and VMH in ASR, and that the dysfunctions revealed by sexual behavior can be overcome by fetal POA or HPT grafting.
C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892.
RP TSAI, YF (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT PHYSIOL,1 JEN AI RD,1ST SECT,TAIPEI 10018,TAIWAN.
NR 24
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCI PUBL IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAY 5
PY 1995
VL 190
IS 2
BP 97
EP 100
DI 10.1016/0304-3940(95)11510-4
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA QY447
UT WOS:A1995QY44700007
PM 7644131
ER

PT J
AU FERNANDEZSALGUERO, P
   PINEAU, T
   HILBERT, DM
   MCPHAIL, T
   LEE, SST
   KIMURA, S
   NEBERT, DW
   RUDIKOFF, S
   WARD, JM
   GONZALEZ, FJ
AF FERNANDEZSALGUERO, P
   PINEAU, T
   HILBERT, DM
   MCPHAIL, T
   LEE, SST
   KIMURA, S
   NEBERT, DW
   RUDIKOFF, S
   WARD, JM
   GONZALEZ, FJ
TI IMMUNE-SYSTEM IMPAIRMENT AND HEPATIC-FIBROSIS IN MICE LACKING THE
   DIOXIN-BINDING AH RECEPTOR
SO SCIENCE
LA English
DT Article
ID TRANSCRIPTIONAL ACTIVATION; GENETIC-DIFFERENCES;
   2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; EXPRESSION; CLONING; CANCER;
   TOXICITY; LOCUS; CDNA
AB The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr(-/-)) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr(-/-) mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr(-/-) mice were reduced in size by 50 percent and showed bile duct fibrosis. Ahr(-/-) mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds, Thus, the AHR plays an important role in the development of the liver and the immune system.
C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892.
   NCI,GENET LAB,BETHESDA,MD 20892.
   NIMH,MOLEC GENET UNIT,BETHESDA,MD 20892.
   UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267.
   NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702.
OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027
FU NIEHS NIH HHS [P30 ES06096, R01 ES06811]
NR 34
TC 704
Z9 717
U1 4
U2 15
PU AMER ASSOC ADVAN SCIENCE
PI WASHINGTON
PA 1333 H ST NW, WASHINGTON, DC 20005
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 5
PY 1995
VL 268
IS 5211
BP 722
EP 726
DI 10.1126/science.7732381
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QW603
UT WOS:A1995QW60300050
PM 7732381
ER

PT J
AU CARDELLINA, JH
   BOKESCH, HR
   MCKEE, TC
   BOYD, MR
AF CARDELLINA, JH
   BOKESCH, HR
   MCKEE, TC
   BOYD, MR
TI RESOLUTION AND COMPARATIVE ANTI-HIV EVALUATION OF THE ENANTIOMERS OF
   CALANOLIDE-A AND CALANOLIDE-B
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
AB Methods for the chiral resolution of (+)-calanolide A and (-)-calanolide A from synthetic (+/-)-calanolide A, and of (+)-calanolide B and (-)-calanolide B (costatolide) from a scalemic mixture isolated from C. lanigerium, have been developed. Calanolide A was originally isolated as the pure (+) enantiomer from C. lanigerum, but now is also shown to occur as a scalemic mixture in latex of C. teysmannii. Interestingly, (+)-calanolide A and (-)-calanolide B are potent HIV-1 inhibitors, while (-)-calanolide A and (+)-calanolide B are inactive against the virus.
C1 NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702.
NR 9
TC 45
Z9 46
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAY 4
PY 1995
VL 5
IS 9
BP 1011
EP 1014
DI 10.1016/0960-894X(95)00158-P
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA QY929
UT WOS:A1995QY92900020
ER

PT J
AU SALESIOTIS, AN
   WANG, CK
   WANG, CD
   BURGER, A
   LI, H
   SETH, A
AF SALESIOTIS, AN
   WANG, CK
   WANG, CD
   BURGER, A
   LI, H
   SETH, A
TI IDENTIFICATION OF NOVEL GENES FROM STOMACH-CANCER CELL-LINES BY
   DIFFERENTIAL DISPLAY
SO CANCER LETTERS
LA English
DT Article
DE GASTRIC CANCER; TUMOR MARKERS; METASTATIC; RNA EXPRESSION
ID POLYMERASE CHAIN-REACTION; GASTRIC-CANCER; MITOCHONDRIA; SENSITIVITY;
   MUTATIONS; TUMORS
AB Gastric cancer is a leading cause of cancer death in many parts of the world. None of the tumor markers available to date provide for a reliable screening/diagnostic test. By using differential display technology on gastric cancer nonmetastatic (RFI) and metastatic (RF48) cell lines, we have isolated six novel cDNA clones. Five of them have not been previously identified. However, one of them appears to be the human homolog of the bovine oligomycin sensitivity conferral protein (oscp). Northern blot analysis showed that this clone is expressed at a much higher level in the metastatic (RF48) than the nonmetastatic (RF1) cancer cell line from the same patient. High level expression of the same gene is also observed in the breast cancer cell lines BT20 and T47D. The other five novel clones isolated showed either low or no expression in the RF1 and RF48 gastric cell lines, but variable levels of expression were detectable in breast cancers cell lines and normal tissues.
C1 TAIPEI MUNICIPAL JEN AI HOSP,DEPT PATHOL,TAIPEI,TAIWAN.
   NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702.
   NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702.
NR 29
TC 22
Z9 22
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 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD MAY 4
PY 1995
VL 91
IS 1
BP 47
EP 54
DI 10.1016/0304-3835(95)03717-B
PG 8
WC Oncology
SC Oncology
GA QY140
UT WOS:A1995QY14000007
PM 7750094
ER

PT J
AU ALVAREZSALAS, LM
   VELAZQUEZ, A
   LOPEZBAYGHEN, E
   WOODWORTH, CD
   GARRIDO, E
   GARIGLIO, P
   DIPAOLO, JA
AF ALVAREZSALAS, LM
   VELAZQUEZ, A
   LOPEZBAYGHEN, E
   WOODWORTH, CD
   GARRIDO, E
   GARIGLIO, P
   DIPAOLO, JA
TI TRANSCRIPTIONAL REPRESSION IN NORMAL HUMAN KERATINOCYTES BY WILD-TYPE
   AND MUTANT P53
SO CANCER LETTERS
LA English
DT Article
DE P53 MUTATION; EPITHELIAL CELLS; TATA BOX; HUMAN PAPILLOMAVIRUS
ID HUMAN PAPILLOMAVIRUS TYPE-16; CARCINOMA CELL-LINES; TATA-BINDING
   PROTEIN; TUMOR-CELLS; GENE AMPLIFICATION; E6 PROTEINS; EXPRESSION;
   PROMOTERS; GROWTH; DNA
AB Wild-type p53 is a nuclear phosphoprotein that inhibits cell proliferation and represses transcriptionally most TATA box-containing promoters in transformed or tumor-derived cell lines. This study demonstrates that p53 alters transcription of the long control region (LCR) of human papillomavirus type 18 (HPV-18), Wild-type and mutant p53 143(Val to Ala) repressed the HPV-18 LCR promoter in normal human keratinocytes, the natural host cell for HPV infections. Repression by wild-type p53 was also observed in C-33A cells and in an HPV-16-immortalized cell line with an inducible wild-type p53, However, when C-33A cells were cotransfected with the HPV-18 LCR and mutant 143(Val to Ala), repression did not occur. Mutant p53 135(Cys to Ser) did not induce repression in either normal human keratinocytes or in the C-33A line; although like 143(Val to Ala), it is thought to affect the DNA binding activity of the wild-type protein. The ability of mutant p53 143(Val to Ala) to inactivate the HPV early promoter in normal cells (by approximately 60% reduction) suggests that this mutant may be able to associate with wild-type p53 and interact with TATA box-binding proteins, Therefore, these results demonstrate that the transcriptional activities of p53 mutants may be dependent upon the cell type assayed and the form of its endogenous p53, Furthermore, normal human keratinocytes represent an alternative model for determining the activities of p53 mutants.
C1 INST POLITECN NACL,CTR INVEST & ESTUDIOS AVANZADOS,DEPT GENET & BIOL MOLEC,MEXICO CITY 07000,DF,MEXICO.
RP ALVAREZSALAS, LM (reprint author), NCI,BIOL LAB,BLDG 37,ROOM 2A19,BETHESDA,MD 20892, USA.
OI Lopez-Bayghen, Esther/0000-0002-2849-7587
NR 46
TC 5
Z9 5
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 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD MAY 4
PY 1995
VL 91
IS 1
BP 85
EP 92
DI 10.1016/0304-3835(95)03721-8
PG 8
WC Oncology
SC Oncology
GA QY140
UT WOS:A1995QY14000012
PM 7750099
ER

PT J
AU LONDON, ED
   SCHEFFEL, U
   KIMES, AS
   KELLAR, KJ
AF LONDON, ED
   SCHEFFEL, U
   KIMES, AS
   KELLAR, KJ
TI IN-VIVO LABELING OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN BRAIN WITH
   [H-3] EPIBATIDINE
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Note
DE NICOTINIC ACETYLCHOLINE RECEPTOR; BRAIN IMAGING; ALZHEIMERS DISEASE
ID BINDING
AB In vivo imaging of nicotinic acetylcholine receptors in brain has been hampered by lack of an adequate radioligand. In the present study, [H-3]epibatidine was administered to mice intravenously, and its time-course in brain regions and sensitivity to blockade by nicotinic drugs were studied. The distribution of radioligand accumulation in brain, and the pharmacological characteristics of binding indicate that radiolabeled forms of epibatidine would be exceptionally promising ligands for the study of nicotinic acetylcholine receptors in vivo.
C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205.
   UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201.
   GEORGETOWN UNIV,SCH MED,WASHINGTON,DC.
RP LONDON, ED (reprint author), NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA.
NR 7
TC 38
Z9 38
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD MAY 4
PY 1995
VL 278
IS 1
BP R1
EP R2
DI 10.1016/0014-2999(95)00178-N
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA QX800
UT WOS:A1995QX80000014
PM 7664806
ER

PT J
AU CARAGLIA, M
   LEARDI, A
   CORRADINO, S
   CIARDIELLO, F
   BUDILLON, A
   GUARRASI, R
   BIANCO, AR
   TAGLIAFERRI, P
AF CARAGLIA, M
   LEARDI, A
   CORRADINO, S
   CIARDIELLO, F
   BUDILLON, A
   GUARRASI, R
   BIANCO, AR
   TAGLIAFERRI, P
TI ALPHA-INTERFERON POTENTIATES EPIDERMAL GROWTH-FACTOR RECEPTOR-MEDIATED
   EFFECTS ON HUMAN EPIDERMOID CARCINOMA KB CELLS
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
ID TRANSCRIPTION FACTOR; BINDING; ANTIBODIES; CANCER; BETA
AB The molecular mechanisms underlying the growth inhibition of human tumor cells induced by recombinant interferon-alpha (IFN alpha) are mostly unknown. It has been proposed that this effect could be related to down-regulation and/or impaired function of peptide growth factor receptors (PGF-Rs) in tumor cells exposed to IFN alpha. However, we have previously described that IFN alpha-induced growth inhibition of human epidermoid carcinoma cells is paralleled by up-regulation of epidermal growth factor receptor (EGF-R). Here we report that an increase in EGF-R synthesis is detectable after 3 hr of exposure to cytostatic concentration of IFN alpha in epidermoid KB tumor cells. In these experimental conditions IFN alpha does not depress and even potentiates EGF-R function. IFN alpha-treated KB cells retain sensitivity to the cytotoxic activity of the anti-EGF-R 225 monoclonal antibody (MAb), which acts through receptor blockade, and are sensitized to the growth-promoting effect of EGF. EGF-induced tyrosine (tyr) phosphorylation both of total cellular protein extracts and of the immunoprecipitated EGF-R is increased in IFN alpha-treated cells. We conclude that a cross-talk between IFN alpha and EGF occurs in KB cells since IFN alpha, at cytostatic concentration, potentiates the effects mediated by the EGF-R. (C) 1995 Wiley-Liss, Inc.
C1 UNIV NAPLES FEDERICO II,CATTEDRA ONCOL MED,DIPARTIMENTO ENDOCRINOL & ONCOL MOLEC & CLIN,I-80131 NAPLES,ITALY.
   NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892.
RI Caraglia, Michele/N-5670-2015; 
OI Caraglia, Michele/0000-0003-2408-6091; Ciardiello,
   Fortunato/0000-0002-3369-4841; Budillon, Alfredo/0000-0002-6330-6053
NR 21
TC 39
Z9 39
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 4
PY 1995
VL 61
IS 3
BP 342
EP 347
DI 10.1002/ijc.2910610312
PG 6
WC Oncology
SC Oncology
GA QV833
UT WOS:A1995QV83300011
PM 7729946
ER

PT J
AU SUN, Y
   HILDESHEIM, A
   LI, H
   LANIER, AP
   CAO, Y
   YAO, KT
   YANG, CS
   COLBURN, NH
AF SUN, Y
   HILDESHEIM, A
   LI, H
   LANIER, AP
   CAO, Y
   YAO, KT
   YANG, CS
   COLBURN, NH
TI THE VON HIPPEL-LINDAU (VHL) DISEASE TUMOR-SUPPRESSOR GENE IS NOT MUTATED
   IN NASOPHARYNGEAL CARCINOMAS
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Letter
ID P53; PCR
C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702.
   NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892.
   FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD.
   ALASKA AREA NATIVE HLTH SERV,INDIAN HLTH SERV,PUBL HLTH SERV,ANCHORAGE,AK.
   HUNAN MED UNIV,HUNAN CANC INST,HUNAN,PEOPLES R CHINA.
   NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI,TAIWAN.
NR 19
TC 11
Z9 13
U1 0
U2 3
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 4
PY 1995
VL 61
IS 3
BP 437
EP 438
DI 10.1002/ijc.2910610327
PG 2
WC Oncology
SC Oncology
GA QV833
UT WOS:A1995QV83300026
PM 7729959
ER

PT J
AU LUNARDIISKANDAR, Y
   BRYANT, JL
   ZEMAN, RA
   LAM, VH
   SAMANIEGO, F
   BESNIER, JM
   HERMANS, P
   THIERRY, AR
   GILL, P
   GALLO, RC
AF LUNARDIISKANDAR, Y
   BRYANT, JL
   ZEMAN, RA
   LAM, VH
   SAMANIEGO, F
   BESNIER, JM
   HERMANS, P
   THIERRY, AR
   GILL, P
   GALLO, RC
TI TUMORIGENESIS AND METASTASIS OF NEOPLASTIC KAPOSIS-SARCOMA CELL-LINE IN
   IMMUNODEFICIENT MICE BLOCKED BY A HUMAN-PREGNANCY HORMONE
SO NATURE
LA English
DT Article
ID HUMAN CHORIONIC-GONADOTROPIN; LONG-TERM CULTURE; GROWTH-FACTOR;
   EXPRESSION; MECHANISMS; AUTOCRINE; PARACRINE; INVITRO; DEATH; HTLV
AB KAPOSI's sarcoma (KS) occurs more often in men than in women and HIV-1-associated KS has a high occurrence in homosexual men (over 30%). Most cultures of KS tumours yield cells with properties of hyperplastic (not malignant) endothelial cells under the control of several cytokines(1-7). The role of HIV-1 may be in promoting high levels of some cytokines and providing stimulation to angiogenesis by the HIV-1 Tat protein(8), which synergizes with basic fibroblast growth factor in promoting these effects(9), Here,ve describe an immortalized AIDS-KS cell line (KS Y-1) and show that these cells produce malignant metastatic tumours in nude mice and are killed in vitro and in vivo (apparently by apoptosis) by a pregnancy hormone, the beta-chain of human chorionic gonadotropin. Similarly, chorionic gonadotropin kills KS SLK, cells from another neoplastic cell line (established from a non-HIV-associated KS)(10), as well as the hyperplastic KS cells from clinical specimens grown in short-term culture, but does not kill normal endothelial cells, These results provide evidence that KS can evolve into a malignancy and have implications for the hormonal treatment of this tumour.
C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892.
   NIDR,ANIM CARE UNIT,BETHESDA,MD 20892.
   GYNECOL & OBSTET MED CTR,F-75017 PARIS,FRANCE.
   FREE UNIV BRUSSELS,HOP ST PIERRE,DEPT MALAD INFECT,B-1000 BRUSSELS,BELGIUM.
   UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033.
RI thierry, alain/F-9492-2014
NR 26
TC 198
Z9 202
U1 0
U2 1
PU MACMILLAN MAGAZINES LTD
PI LONDON
PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF
SN 0028-0836
J9 NATURE
JI Nature
PD MAY 4
PY 1995
VL 375
IS 6526
BP 64
EP 68
DI 10.1038/375064a0
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA QW604
UT WOS:A1995QW60400056
PM 7723844
ER

PT J
AU ALIMANDI, M
   ROMANO, A
   CURIA, MC
   MURARO, R
   FEDI, P
   AARONSON, SA
   DIFIORE, PP
   KRAUS, MH
AF ALIMANDI, M
   ROMANO, A
   CURIA, MC
   MURARO, R
   FEDI, P
   AARONSON, SA
   DIFIORE, PP
   KRAUS, MH
TI COOPERATIVE SIGNALING OF ERBB3 AND ERBB2 IN NEOPLASTIC TRANSFORMATION
   AND HUMAN MAMMARY CARCINOMAS
SO ONCOGENE
LA English
DT Article
DE ERBB RECEPTOR FAMILY; ONCOGENES; TYROSINE PHOSPHORYLATION;
   HETERODIMERIZATION; PI3-KINASE
ID TYROSINE KINASE-ACTIVITY; HUMAN-BREAST-CARCINOMA; FACTOR RECEPTOR
   FAMILY; HER-2 NEU ONCOGENE; EGF RECEPTOR; PROTO-ONCOGENE; C-ERBB-2
   ONCOGENE; POINT MUTATION; BETA-ACTIN; CELLS
AB In the present study we demonstrate that erbB-3 and erbB-2 cooperate in neoplastic transformation. Under conditions in which neither gene alone induced transformation, they readily transformed NIH3T3 cells if coexpressed. Furthermore, at high expression levels of ErbB2 which cause transformation, ErbB3 enhanced focus formation by one order of magnitude. Synergy required an intact ErbB2 extracellular domain and tyrosine kinase activity. Cooperation between ErbB3 and ErbB2 involved heterodimerization and increased tyrosine phosphorylation of ErbB3. Signaling by the heterodimer resulted in increased PI 3-kinase recruitment as web as quantitative and qualitative differences in substrate phosphorylation. Evidence for signaling by an active ErbB3-ErbB2 heterodimer in four mammary tumor cell lines indicated relevance of this mechanism for human neoplasia. Our detection of the NDF/heregulin transcript in NIH3T3 cells implicates an autocrine loop involving this ligand in signaling by the ErbB3-ErbB2 heterodimer in the model system, whereas heregalin-independent mechanisms likely exist for cooperative signaling by ErbB3 and ErhB2 chronically activated in some human mammary carcinomas.
C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA.
   NCI, EXPTL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA.
   UNIV G DANNUNZIO, IST PATOL UMANA & MED SOCIALE, I-66013 CHIETI, ITALY.
   MT SINAI MED CTR, DERALD H RUTTENBERG CANC CTR, NEW YORK, NY 10029 USA.
RI Di Fiore, Pier Paolo/K-2130-2012
OI Di Fiore, Pier Paolo/0000-0002-2252-0950
NR 51
TC 450
Z9 455
U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAY 4
PY 1995
VL 10
IS 9
BP 1813
EP 1821
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA QX469
UT WOS:A1995QX46900014
PM 7538656
ER

PT J
AU HARRIS, T
   HAVLIK, R
   ETTINGER, WH
AF HARRIS, T
   HAVLIK, R
   ETTINGER, WH
TI CHOLESTEROL AND CORONARY HEART-DISEASE RISK IN ELDERLY PATIENTS
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID OLDER
C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC.
RP HARRIS, T (reprint author), NIA,BETHESDA,MD 20892, USA.
NR 6
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 3
PY 1995
VL 273
IS 17
BP 1329
EP 1329
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA QV307
UT WOS:A1995QV30700005
PM 7715051
ER

PT J
AU PROVINCE, MA
   HADLEY, EC
   HORNBROOK, MC
   LIPSITZ, LA
   MULROW, CD
   ORY, MG
   SATTIN, RW
   TINETTI, ME
   WOLF, SL
AF PROVINCE, MA
   HADLEY, EC
   HORNBROOK, MC
   LIPSITZ, LA
   MULROW, CD
   ORY, MG
   SATTIN, RW
   TINETTI, ME
   WOLF, SL
TI THE EFFECTS OF EXERCISE ON FALLS IN ELDERLY PATIENTS - A PREPLANNED
   METAANALYSIS OF THE FICSIT TRIALS
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID FUNCTIONAL STATUS; OLDER PERSONS; RISK-FACTORS; POPULATION; FRAILTY;
   PREDICTORS; COMMUNITY; INJURIES; BALANCE; PEOPLE
AB Objective.-To determine if short-term exercise reduces falls and fall-related injuries in the elderly.
   Design.-A preplanned meta-analysis of the seven Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT)-independent, randomized, controlled clinical trials that assessed intervention efficacy in reducing falls and frailty in elderly patients. All included an exercise component for 10 to 36 weeks. Fall and injury follow-up was obtained for up to 2 to 4 years.
   Setting.-Two nursing home and five community-dwelling (three health maintenance organizations) sites. Six were group and center based; one was conducted at home.
   Participants.-Numbers of participants ranged from 100 to 1323 per study. Subjects were mostly ambulatory and cognitively intact, with minimum ages of 60 to 75 years, although some studies required additional deficits, such as functionally dependent in two or more activities of daily living, balance deficits or lower extremity weakness, or high risk of falling.
   Interventions.-Exercise components varied across studies in character, duration, frequency, and intensity. Training was performed in one area or more of endurance, flexibility, balance platform, Tai Chi (dynamic balance), and resistance. Several treatment arms included additional nonexercise components, such as behavioral components, medication changes, education, functional activity, or nutritional supplements.
   Main Outcome Measures.-Time to each fall (fall-related injury) by self-report and/or medical records.
   Results.-Using the Andersen-Gill extension of the Cox model that allows multiple fall outcomes per patient, the adjusted fall incidence ratio for treatment arms including general exercise was 0.90 (95% confidence limits [CL], 0.81, 0.99) and for those including balance was 0.83 (95% CL, 0.70, 0.98). No exercise component was significant for injurious falls, but power was low to detect this outcome.
   Conclusions.-Treatments including exercise for elderly adults reduce the risk of falls.
C1 NIA,BETHESDA,MD 20892.
   KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR.
   HARVARD UNIV,BETH ISRAEL HOSP,HEBREW REHABIL CTR AGED,BOSTON,MA 02215.
   AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX.
   CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341.
   YALE UNIV,SCH MED,PROGRAM AGING,NEW HAVEN,CT.
   EMORY UNIV,SCH MED,DEPT REHABIL MED,ATLANTA,GA.
RP PROVINCE, MA (reprint author), WASHINGTON UNIV,SCH MED,DIV BIOSTAT,BOX 8067,600 S EUCLID ST,ST LOUIS,MO 63110, USA.
RI Wolf, Steven/F-6588-2010; 
OI Wolf, Steven/0000-0002-9446-8995; Miller, J Philip/0000-0003-4568-6846
NR 44
TC 643
Z9 658
U1 28
U2 82
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 MAY 3
PY 1995
VL 273
IS 17
BP 1341
EP 1347
DI 10.1001/jama.273.17.1341
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA QV307
UT WOS:A1995QV30700018
PM 7715058
ER

PT J
AU FLEG, JL
   SHAPIRO, EP
   OCONNOR, F
   TAUBE, J
   GOLDBERG, AP
   LAKATTA, EG
AF FLEG, JL
   SHAPIRO, EP
   OCONNOR, F
   TAUBE, J
   GOLDBERG, AP
   LAKATTA, EG
TI LEFT-VENTRICULAR DIASTOLIC FILLING PERFORMANCE IN OLDER MALE-ATHLETES
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ECHOCARDIOGRAPHIC MEASUREMENTS; HEART-RATE; EXERCISE; AGE; HYPERTROPHY;
   CONTRACTION; POPULATION; INDEXES; PRELOAD; HUMANS
AB Objective.-To determine whether older men who have undergone intensive endurance training over many years demonstrate less age-associated impairment of early diastolic left ventricular (LV) filling performance than their sedentary peers.
   Design.-Cross-sectional prospective study.
   Setting.-Community-dwelling research volunteers.
   Participants.-Sixteen older competitive male endurance athletes aged 52 through 76 years and 17 young (40 years) and 23 older (52 through 76 years) sedentary control subjects from the Baltimore Longitudinal Study of Aging.
   Intervention.-All subjects underwent resting Doppler echocardiography and determination of maximal aerobic capacity (Vo(2)max) during graded treadmill exercise. Doppler echocardiographic studies were interpreted without knowledge of the subject's age or exercise habits.
   Main Outcome Measures.-Doppler-derived measures of LV diastolic filling performance: peak early (E) filling velocity, peak late (A) filling velocity, ratio of peak E to peak A velocities (E/A), and atrial filling fraction.
   Results.-Older athletes demonstrated higher Vo(2)max (47+/-6 mL/kg per minute [mean+/-SD]) than either the young controls (41 +/-7 mL/kg per minute) or older controls (30+/-7 mL/kg per minute) (P<.05) as evidence of their superior conditioning status. However, peak E diastolic LV filling velocity was higher in young controls (79+/-17 cm/s) than in older athletes (56+/-15 cm/s) or older controls 68+/-18 cm/s) (P<.001). This age difference persisted after normalizing peak E velocity for mitral stroke volume. Peak EIA ratio and atrial filling fraction were also similar in older athletes (1.2+/-0.5 and 0.41+/-0.1, respectively) and older controls (1.1+/-0.4 and 0.41+/-0.1, respectively), and differed significantly from corresponding values of 1.7+/-0.4 and 0.33+/-0.1 in young controls (P<.001 and P<.05, respectively), By multiple regression analysis, age but not treadmill Vo(2)max was a significant predictor of peak E velocity, peak A velocity, peak E/A ratio, and atrial filling fraction.
   Conclusion.-Older men with a long history of intensive endurance training demonstrate impaired early diastolic LV filling similar to that of their sedentary peers. Thus, impairment of early diastolic filling appears to be intrinsic to normative aging and not secondary to the reduction in aerobic capacity that accompanies the aging process.
C1 JOHNS HOPKINS UNIV,BAYVIEW MED CTR,DIV CARDIOL,BALTIMORE,MD.
   UNIV MARYLAND,SCH MED,DIV GERONTOL,BALTIMORE,MD.
RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA.
FU NIA NIH HHS [R01-AG-07660, AG-04402]
NR 36
TC 67
Z9 67
U1 1
U2 4
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 MAY 3
PY 1995
VL 273
IS 17
BP 1371
EP 1375
DI 10.1001/jama.273.17.1371
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA QV307
UT WOS:A1995QV30700023
PM 7715063
ER

PT J
AU HADLEY, EC
AF HADLEY, EC
TI THE SCIENCE OF THE ART OF GERIATRIC-MEDICINE
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ELDERLY PATIENTS; OLDER ADULTS; PHYSICAL-ACTIVITY; HEALTH-STATUS;
   FICSIT; EXERCISE; FRAILTY; FALLS; COMMUNITY; STRENGTH
RP HADLEY, EC (reprint author), NIA,GERIATR PROGRAM,GATEWAY BLDG,SUITE 3E327,BETHESDA,MD 20892, USA.
NR 40
TC 7
Z9 7
U1 16
U2 16
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 MAY 3
PY 1995
VL 273
IS 17
BP 1381
EP 1383
DI 10.1001/jama.273.17.1381
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA QV307
UT WOS:A1995QV30700025
PM 7715065
ER

PT J
AU YORK, DM
   YANG, WT
   LEE, H
   DARDEN, T
   PEDERSEN, LG
AF YORK, DM
   YANG, WT
   LEE, H
   DARDEN, T
   PEDERSEN, LG
TI TOWARD THE ACCURATE MODELING OF DNA - THE IMPORTANCE OF LONG-RANGE
   ELECTROSTATICS
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Note
ID MOLECULAR-DYNAMICS; B-DNA; FORCE-FIELD; NUCLEIC-ACIDS; SIMULATIONS;
   D(CGCGAATTCGCG)2; DODECAMER; EWALD; WATER
C1 N CAROLINA SUPERCOMP CTR,RES TRIANGLE PK,NC 27709.
   NIEHS,RES TRIANGLE PK,NC 27709.
   UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599.
RP YORK, DM (reprint author), DUKE UNIV,DEPT CHEM,DURHAM,NC 27706, USA.
RI Yang, Weitao/C-1109-2008; Pedersen, Lee/E-3405-2013
OI Pedersen, Lee/0000-0003-1262-9861
NR 21
TC 161
Z9 163
U1 0
U2 10
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 MAY 3
PY 1995
VL 117
IS 17
BP 5001
EP 5002
DI 10.1021/ja00122a034
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA QW140
UT WOS:A1995QW14000034
ER

PT J
AU SIMON, R
AF SIMON, R
TI DISCOVERING THE TRUTH ABOUT TAMOXIFEN - PROBLEMS OF MULTIPLICITY IN
   STATISTICAL EVALUATION OF BIOMEDICAL DATA
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CLINICAL-TRIALS
C1 NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,BETHESDA,MD.
RP SIMON, R (reprint author), NIH,EXECUT PLAZA N,RM 739,ROCKVILLE,MD 20852, USA.
NR 8
TC 8
Z9 8
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 MAY 3
PY 1995
VL 87
IS 9
BP 627
EP 629
DI 10.1093/jnci/87.9.627
PG 3
WC Oncology
SC Oncology
GA QV014
UT WOS:A1995QV01400002
PM 7752263
ER

PT J
AU HAYES, RB
AF HAYES, RB
TI ARE DIETARY-FAT AND VASECTOMY RISK-FACTORS FOR PROSTATE-CANCER
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID UNITED-STATES MEN; RETROSPECTIVE COHORT; BETA-CAROTENE; PREVENTION;
   CONSUMPTION; NUTRITION; DISEASE; BLACKS; WHITES
RP HAYES, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC ETIOL,BETHESDA,MD 20895, USA.
NR 51
TC 6
Z9 6
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 MAY 3
PY 1995
VL 87
IS 9
BP 629
EP 631
DI 10.1093/jnci/87.9.629
PG 3
WC Oncology
SC Oncology
GA QV014
UT WOS:A1995QV01400003
PM 7752264
ER

PT J
AU VARMUS, HE
AF VARMUS, HE
TI AN OVERVIEW OF THE FY-1996 BUDGET FOR THE NATIONAL-INSTITUTES-OF-HEALTH
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
RP VARMUS, HE (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HANLEY & BELFUS INC
PI PHILADELPHIA
PA 210 S 13TH ST, PHILADELPHIA, PA 19107
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD MAY
PY 1995
VL 70
IS 5
BP 385
EP 387
DI 10.1097/00001888-199505000-00014
PG 3
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA QZ280
UT WOS:A1995QZ28000019
PM 7748383
ER

PT J
AU BOERI, E
   ABECASIS, C
   VARNIER, OE
   FRANCHINI, G
AF BOERI, E
   ABECASIS, C
   VARNIER, OE
   FRANCHINI, G
TI ANALYSIS OF HTLV-I ENV GENE SEQUENCE FROM AN ITALIAN POLYTRANSFUSED
   PATIENT - EVIDENCE FOR A ZAIRIAN HTLV-I IN SICILY
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Note
ID VIRUS TYPE-I; COMPLETE NUCLEOTIDE-SEQUENCE; TROPICAL SPASTIC
   PARAPARESIS; CELL LEUKEMIA-VIRUS; ISOLATE; ORIGIN
C1 UNIV GENOA,IST ONCOL CLIN & SPERIMENTALE,CTR BIOTECHNOL AVANZATE,VIROL BIOMOLEC LAB,I-16132 GENOA,ITALY.
   NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892.
RP BOERI, E (reprint author), UNIV MILAN,OSPED SAN RAFFAELE,CTR S LUIGI,VIROL LAB,VIA STAMIRA ANCONA 20,I-20127 MILAN,ITALY.
NR 11
TC 5
Z9 5
U1 0
U2 0
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 1995
VL 11
IS 5
BP 649
EP 651
DI 10.1089/aid.1995.11.649
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA RA347
UT WOS:A1995RA34700015
PM 7576922
ER

PT J
AU FIGUEROA, JB
   BREEN, N
AF FIGUEROA, JB
   BREEN, N
TI SIGNIFICANCE OF UNDERCLASS RESIDENCE ON THE STAGE OF BREAST OR
   CERVICAL-CANCER DIAGNOSIS
SO AMERICAN ECONOMIC REVIEW
LA English
DT Article; Proceedings Paper
CT 107th Annual Meeting of the American-Economic-Association
CY JAN 05-08, 1995
CL WASHINGTON, DC
SP Amer Econ Assoc
ID HEALTH
C1 NCI,DIV CANC BIOL,APPL RES BRANCH,BETHESDA,MD 20892.
RP FIGUEROA, JB (reprint author), FORDHAM UNIV,DEPT SOCIAL SCI,113 W 60TH ST,NEW YORK,NY 10023, USA.
NR 13
TC 16
Z9 16
U1 0
U2 1
PU AMER ECON ASSN
PI NASHVILLE
PA 2014 BROADWAY SUITE 305, NASHVILLE, TN 37203
SN 0002-8282
J9 AM ECON REV
JI Am. Econ. Rev.
PD MAY
PY 1995
VL 85
IS 2
BP 112
EP 116
PG 5
WC Economics
SC Business & Economics
GA RB651
UT WOS:A1995RB65100024
PM 10160521
ER

PT J
AU TATARANNI, PA
   LARSON, DE
   SNITKER, S
   RAVUSSIN, E
AF TATARANNI, PA
   LARSON, DE
   SNITKER, S
   RAVUSSIN, E
TI THERMAL EFFECT OF FOOD IN HUMANS - METHODS AND RESULTS FROM USE OF A
   RESPIRATORY CHAMBER
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE ENERGY EXPENDITURE; THERMOGENESIS; OBESITY; PREDICTORS OF WEIGHT GAIN
ID DIET-INDUCED THERMOGENESIS; MEAL-INDUCED THERMOGENESIS; GLUCOSE-INDUCED
   THERMOGENESIS; SYMPATHETIC NERVOUS-SYSTEM; ENERGY-EXPENDITURE; OBESE
   SUBJECTS; INDIRECT CALORIMETRY; METABOLIC-RATE; BODY-WEIGHT; INSULIN
AB During the past two decades, many investigators have measured the thermic effect of food (TEF) in humans and have speculated on its role in the development of obesity. In this study we compared different ways of computing TEF from daily energy expenditure measurements in a respiratory chamber, evaluated the determinants of TEF, and more importantly assessed for the first time the relation between TEF and change in body weight. In 471 subjects, TEF was 1697 +/- 857 kJ/d (($) over bar x +/- SD), ie, 18 +/- 9% of energy intake. In 114 subjects studied more than once, intraindividual TEF variability was very high (CV = 48%). TEF correlated positively with the level of spontaneous physical activity (SPA) and negatively with fasting plasma glucose and insulin concentrations. TEF correlated inversely with age (males only) and body weight, percent body fat, and waist-to-hip ratio (females only). The level of SPA and fasting plasma glucose concentration were the only significant determinants of TEF, explaining 15% of its variance. In 137 subjects in whom body weight was measured greater than or equal to 6 mo after TEF measurement (mean follow-up duration of 2.9 +/- 1.7 y), a low TEF was not predictive of body weight gain. We conclude that, despite the low reproducibility of TEF from use of a respiratory chamber, data in a large number of subjects suggest that TEF is increased by higher SPAs and that insulin resistance is associated with a low TEF. More important, longitudinal data indicate that the variability in TEF is not associated with changes in body weight.
RP TATARANNI, PA (reprint author), NIDDK,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016, USA.
NR 42
TC 66
Z9 66
U1 0
U2 2
PU AMER SOC CLIN NUTRITION INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAY
PY 1995
VL 61
IS 5
BP 1013
EP 1019
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA QV695
UT WOS:A1995QV69500001
PM 7733021
ER

PT J
AU CHAN, JKC
   BANKS, PM
   CLEARY, ML
   DELSOL, G
   DEWOLFPEETERS, C
   FALINI, B
   GATTER, KC
   GROGAN, TM
   HARRIS, NL
   ISAACSON, PG
   JAFFE, ES
   KNOWLES, DM
   MASON, DY
   MULLERHERMELINK, HK
   PILERI, SA
   PIRIS, MA
   RALFKIAER, E
   STEIN, H
   WARNKE, RA
AF CHAN, JKC
   BANKS, PM
   CLEARY, ML
   DELSOL, G
   DEWOLFPEETERS, C
   FALINI, B
   GATTER, KC
   GROGAN, TM
   HARRIS, NL
   ISAACSON, PG
   JAFFE, ES
   KNOWLES, DM
   MASON, DY
   MULLERHERMELINK, HK
   PILERI, SA
   PIRIS, MA
   RALFKIAER, E
   STEIN, H
   WARNKE, RA
TI A REVISED EUROPEAN-AMERICAN CLASSIFICATION OF LYMPHOID NEOPLASMS
   PROPOSED BY THE INTERNATIONAL LYMPHOMA STUDY-GROUP - A SUMMARY VERSION
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
C1 UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA.
   STANFORD UNIV, SCH MED, DEPT PATHOL, STANFORD, CA 94305 USA.
   UNIV TOULOUSE 3, FAC MED PURPAN, DEPT PATHOL, F-31062 TOULOUSE, FRANCE.
   CATHOLIC UNIV LEUVEN, DEPT PATHOL, B-3000 LOUVAIN, BELGIUM.
   UNIV PERUGIA, INST HEMATOL, DEPT PATHOL, I-06100 PERUGIA, ITALY.
   UNIV OXFORD, JOHN RADCLIFFE HOSP, DEPT PATHOL, OXFORD OX3 9DU, ENGLAND.
   UNIV ARIZONA, SCH MED, DEPT PATHOL, TUCSON, AZ 85721 USA.
   HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA.
   NCI, DEPT PATHOL, BETHESDA, MD 20892 USA.
   CORNELL UNIV, MED CTR, NEW YORK HOSP, DEPT PATHOL, NEW YORK, NY 10021 USA.
   UNIV WURZBURG, DEPT PATHOL, W-8700 WURZBURG, GERMANY.
   UNIV BOLOGNA, DEPT PATHOL, BOLOGNA, ITALY.
   HOSP VIRGEN SALUD, DEPT PATHOL, TOLEDO, SPAIN.
   UNIV COPENHAGEN, DEPT PATHOL, HERLEV, DENMARK.
   FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT PATHOL, W-1000 BERLIN, GERMANY.
   UCL HOSP, DEPT PATHOL, LONDON, ENGLAND.
   MIDDLESEX HOSP, DEPT PATHOL, LONDON, ENGLAND.
RP CHAN, JKC (reprint author), QUEEN ELIZABETH HOSP, DEPT PATHOL, WYLIE RD, KOWLOON, HONG KONG.
OI Piris, Miguel A/0000-0001-5839-3634
NR 15
TC 94
Z9 98
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD MAY
PY 1995
VL 103
IS 5
BP 543
EP 560
PG 18
WC Pathology
SC Pathology
GA QX171
UT WOS:A1995QX17100003
PM 7741099
ER

PT J
AU DAGOSTINO, RB
   BELANGER, AJ
   KANNEL, WB
   HIGGINS, M
AF DAGOSTINO, RB
   BELANGER, AJ
   KANNEL, WB
   HIGGINS, M
TI ROLE OF SMOKING IN THE U-SHAPED RELATION OF CHOLESTEROL TO MORTALITY IN
   MEN - THE FRAMINGHAM-STUDY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE EPIDEMIOLOGIC METHODS; CHOLESTEROL; SMOKING
ID FACTOR INTERVENTION TRIAL; SERUM-CHOLESTEROL; BLOOD CHOLESTEROL; CANCER
   MORTALITY; FOLLOW-UP; RISK; HEALTH; LEVEL
AB Elevated mortality has been reported at extremes of the serum total cholesterol distribution, with increased coronary mortality reported at high total cholesterol levels and increased cancer and non-cardiovascular/non-cancer mortality at low total cholesterol levels, The authors used data collected on 1,959 males aged 35-69 years from the fourth Framingham Study examination to analyze the relations between total serum cholesterol levels and 409 coronary deaths, 325 cancer deaths, and 534 other deaths for a 32-year follow-up. Age- and risk factor-adjusted Cox regressions were computed, Nonlinear (U-shaped) relations were investigated with the use of quadratic regression and with dummy variables using the 160-199 mg/dl group as the comparison group, Subset analyses investigated the relation in smokers and men who drank greater than or equal to 14 alcoholic drinks per week, All analyses were repeated removing those with existing cardiovascular disease and cancer and those who died during the first 5 years of follow-up, A significant U-shaped relation with all-cause mortality was noted, as were an inverse relation to cancer mortality and a monotonic increasing relation with coronary disease mortality, In subset analyses, the association of low serum cholesterol (<160 mg/dl) with cancer mortality was observed in men who smoked cigarettes, Compared with the 160-199 mg/dl group, the relative risk was 3.72 (p = 0.0001, 95% confidence interval 1.91-7.25). Studies of the relation of low total serum cholesterol levels, cigarette smoking, and cancer are needed.
C1 BOSTON UNIV,SCH MED,EVANS MEM RES FDN,DEPT MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118.
   NHLBI,BETHESDA,MD 20892.
RP DAGOSTINO, RB (reprint author), BOSTON UNIV,DEPT MATH,111 CUMMINGTON ST,BOSTON,MA 02215, USA.
FU NHLBI NIH HHS [N01-HV-92922, N01-HV-52971, R01-HL-40423-5]
NR 26
TC 33
Z9 34
U1 0
U2 0
PU AMER J EPIDEMIOLOGY
PI BALTIMORE
PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAY 1
PY 1995
VL 141
IS 9
BP 822
EP 827
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QV027
UT WOS:A1995QV02700004
PM 7717358
ER

PT J
AU SUBAR, AF
   HEIMENDINGER, J
   PATTERSON, BH
   KREBSSMITH, SM
   PIVONKA, E
   KESSLER, R
AF SUBAR, AF
   HEIMENDINGER, J
   PATTERSON, BH
   KREBSSMITH, SM
   PIVONKA, E
   KESSLER, R
TI FRUIT AND VEGETABLE INTAKE IN THE UNITED-STATES - THE BASE-LINE SURVEY
   OF THE 5 A DAY FOR BETTER HEALTH-PROGRAM
SO AMERICAN JOURNAL OF HEALTH PROMOTION
LA English
DT Article
ID NHANES-II SURVEY; AMERICAN DIET; QUESTIONNAIRE; MACRONUTRIENTS; RECORDS;
   CANCER; ENERGY
AB Purpose.  The purpose of the Five A Day Baseline Survey was to assess fruit and vegetable intake and associated factors among US adults.
   Design.  Questionnaires querying frequency of intake of 33 fruits and vegetables, as well as demographics, attitudes, and knowledge related to fruits and vegetables were administered by telephone.
   Setting.  The study was a nationally representative random digit dial survey conducted by telephone in the summer of 1991; response rate was 42.8%.
   Subjects.  Respondents were 2811 US adults (including an oversample of African-Americans and Hispanics).
   Measures.  Mean and median self-reported intakes of fruits and vegetables were calculated.  Estimated servings per week were adjusted on the basis of responses to summary questions regarding overall fruit and vegetable intakes.
   Results.  Median intake of fruits and vegetables was 3.4 servings per day.  Linear regressions (accounting for no more than 10% of the variation) showed that education, income, and smoking status were predictors of fruit and vegetable intake and that intake increased with education, income, and nonsmoking status.  Women had higher intakes than men at all ages; these differences between men and women increased with age.  Fruit and vegetable intakes increased with age for whites and Hispanics, but not for African-Americans.
   Conclusions.  Fruit and vegetable intake among adults in the United States is lower than the recommended minimum of five daily servings.  These data will be useful in targeting campaign efforts and in assessing progress of the Five A Day for Better Health Program.
C1 UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI 48109.
RP SUBAR, AF (reprint author), NCI,DIV CANC PREVENT & CONTROL,5 DAY BETTER HLTH PROGRAM,BETHESDA,MD 20892, USA.
NR 21
TC 203
Z9 206
U1 1
U2 5
PU MOSBY-YEAR BOOK INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318
SN 0890-1171
J9 AM J HEALTH PROMOT
JI Am. J. Health Promot.
PD MAY-JUN
PY 1995
VL 9
IS 5
BP 352
EP 360
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QX581
UT WOS:A1995QX58100010
PM 10150767
ER

PT J
AU CHOU, YHW
   POLLAK, MR
   BRANDI, ML
   TOSS, G
   ARNQVIST, H
   ATKINSON, AB
   PAPAPOULOS, SE
   MARX, S
   BROWN, EM
   SEIDMAN, JG
   SEIDMAN, CE
AF CHOU, YHW
   POLLAK, MR
   BRANDI, ML
   TOSS, G
   ARNQVIST, H
   ATKINSON, AB
   PAPAPOULOS, SE
   MARX, S
   BROWN, EM
   SEIDMAN, JG
   SEIDMAN, CE
TI MUTATIONS IN THE HUMAN CA2+-SENSING-RECEPTOR GENE THAT CAUSE FAMILIAL
   HYPOCALCIURIC HYPERCALCEMIA
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SEVERE PRIMARY HYPERPARATHYROIDISM; RECEPTOR; KINDREDS
AB We report five novel mutations in the human Ca2+-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation ((228)Arg-->Gln, (139)Thr-->Met, (144)Gly-->Glu, (63)Arg-->Met, and (67)Arg-->Cys) that encodes a nonconservative amino acid alteration, These mutations are each predicted to be in the Ca2+-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca2+-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca2+-sensing-receptor gene can cause FHH.
C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115.
   HARVARD UNIV,HOWARD HUGHES MED INST,BOSTON,MA 02115.
   BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115.
   BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115.
   BRIGHAM & WOMENS HOSP,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115.
   CHANG GUNG MEM HOSP,LIVER RES UNIT,TAYUAN,TAIWAN.
   UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,FLORENCE,ITALY.
   LINKOPING UNIV,DEPT INTERNAL MED,LINKOPING,SWEDEN.
   ROYAL VICTORIA HOSP,SIR GEORGE E CLARK METAB UNIT,BELFAST,ANTRIM,NORTH IRELAND.
   UNIV LEIDEN HOSP,DEPT ENDOCRINOL & METAB DIS,LEIDEN,NETHERLANDS.
   NIDDKD,METAB DIS BRANCH,BETHESDA,MD.
FU NIDDK NIH HHS [DK02138, DK44588, DK46422]
NR 23
TC 98
Z9 100
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAY
PY 1995
VL 56
IS 5
BP 1075
EP 1079
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA QU586
UT WOS:A1995QU58600008
PM 7726161
ER

PT J
AU CHOW, WH
   MCLAUGHLIN, JK
   MALKER, HSR
   LINET, MS
   WEINER, JA
   STONE, BJ
AF CHOW, WH
   MCLAUGHLIN, JK
   MALKER, HSR
   LINET, MS
   WEINER, JA
   STONE, BJ
TI ESOPHAGEAL CANCER AND OCCUPATION IN A COHORT OF SWEDISH MEN
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE OCCUPATIONAL RISKS; ESOPHAGEAL CANCER; REGISTRY LINKAGE STUDY; SWEDEN
ID BRITISH RUBBER INDUSTRY; DEATH CERTIFICATES; MORTALITY; WORKERS;
   FARMERS; DANISH; SWEDEN; RISKS
AB Using the Cancer Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of esophageal cancer incidence by industry and occupation for men in Sweden. A general reduction in esophageal cancer incidence was found among agricultural and professional workers, whereas excess incidence was found among business, sales, and some craftsmen and production jobs. Elevated incidence was associated with several specific industries, including the food (SIR = 1.3, p < 0.05), beverage and tobacco (SIR = 1.8, p < 0.05) industries, vulcanizing shops within the rubber industry (SIR = 4.7, p < 0.01), and certain automotive building industries. Incidence also was increased among brewery workers (SIR = 4.2, p < 0.01) and butchers (SIR = 2.1, p < 0.01), and among individuals with certain service jobs, particularly waiters in the hotel and restaurant industry (SIR = 3.1, p < 0.01). Some of the occupational associations may be explained by lifestyle factors such as alcohol drinking and smoking, whereas others are specific and tend to support those of earlier investigations. This study adds to the evidence of a small but possibly important role of occupation in esophageal cancer etiology. (C) 1995 Wiley-Liss, Inc.*
C1 NCI, PROGRAM EPIDEMIOL, BETHESDA, MD 20892 USA.
   NCI, BIOSTAT PROGRAMS, BETHESDA, MD 20892 USA.
   NATL BOARD OCCUPAT SAFETY & HLTH, SOLNA, SWEDEN.
RP CHOW, WH (reprint author), NCI, DIV CANC ETIOL, 6130 EXECUTIVE BLVD, EPN 415, BETHESDA, MD 20892 USA.
NR 34
TC 13
Z9 13
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
EI 1097-0274
J9 AM J IND MED
JI Am. J. Ind. Med.
PD MAY
PY 1995
VL 27
IS 5
BP 749
EP 757
DI 10.1002/ajim.4700270509
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QU239
UT WOS:A1995QU23900008
PM 7611309
ER

PT J
AU BENVENGA, S
AF BENVENGA, S
TI MORE ON HDL SUBFRACTIONS
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Letter
ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; THYROXINE; BINDING
RP BENVENGA, S (reprint author), NIDDK,GENET & BIOCHEM BRANCH,ENDOCRINOL SECT,BETHESDA,MD, USA.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU CAHNERS PUBL CO
PI NEW YORK
PA 249 WEST 17 STREET, NEW YORK, NY 10011
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD MAY
PY 1995
VL 98
IS 5
BP 514
EP 515
DI 10.1016/S0002-9343(99)80357-X
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA QW864
UT WOS:A1995QW86400019
PM 7733135
ER

PT J
AU BERRY, SM
   PUDER, KS
   BOTTOMS, SF
   UCKELE, JE
   ROMERO, R
   COTTON, DB
AF BERRY, SM
   PUDER, KS
   BOTTOMS, SF
   UCKELE, JE
   ROMERO, R
   COTTON, DB
TI COMPARISON OF INTRAUTERINE HEMATOLOGIC AND BIOCHEMICAL VALUES BETWEEN
   TWIN PAIRS WITH AND WITHOUT STUCK TWIN SYNDROME
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE STUCK TWIN SYNDROME; FETOFETAL TRANSFUSION SYNDROME; CORDOCENTESIS
ID TRANSFUSION SYNDROME; THERAPEUTIC AMNIOCENTESIS; ULTRASOUND; GESTATION;
   CRITERIA
AB OBJECTIVE: Our purpose was to compare hematologic and biochemical values in cordocentesis specimens from twin pairs with and without stuck twin syndrome.
   STUDY DESIGN: Cordocentesis was performed on 38 twin pairs. Assignment to the stuck twin syndrome group (n = 8) was based on ultrasonographic findings of discordant size and amniotic fluid volume, concordant gender, and a single placenta. A receiver-operator characteristic curve was constructed with the use of intertwin hemoglobin differences. For the stuck twin syndrome group regression analysis of gestational age and intertwin hemoglobin difference was done.
   RESULTS: We found significant Co = 0.03) intertwin differences in hemoglobin between the stuck twin syndrome group (mean 5.35 gm/dl, range 0.5 to 15.4 gm/dl) and the comparison group (mean 0.10 gm/dl, range 0.0 to 2.4 gm/dl). A nearly significant relationship between gestational age and intertwin hemoglobin difference was noted in the stuck twin syndrome group. When the hemoglobin difference was >2.4 gm/dl, all cases had stuck twin syndrome (sensitivity = 50%, specificity = 100%, positive predictive value = 100%, negative predictive value = 91%). In the stuck twin syndrome group there was a trend toward larger intertwin differences in albumin and total protein. Intertwin blood gas values between the groups did not differ, but the average Po-2 was lower when the smaller twins of the two groups were compared.
   CONCLUSION: An intertwin difference in hemoglobin >2.4 gm/dl is consistent with stuck twin syndrome. Large intertwin hemoglobin differences and imbalances in albumin and total protein may be seen in stuck twin syndrome.
C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892.
RP BERRY, SM (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA.
NR 18
TC 28
Z9 29
U1 0
U2 0
PU MOSBY-YEAR BOOK INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 1995
VL 172
IS 5
BP 1403
EP 1410
DI 10.1016/0002-9378(95)90469-7
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA QZ874
UT WOS:A1995QZ87400006
PM 7755045
ER

PT J
AU KLEBANOFF, MA
   REGAN, JA
   RAO, AV
   NUGENT, RP
   BLACKWELDER, WC
   ESCHENBACH, DA
   PASTOREK, JG
   WILLIAMS, S
   GIBBS, RS
   CAREY, JC
AF KLEBANOFF, MA
   REGAN, JA
   RAO, AV
   NUGENT, RP
   BLACKWELDER, WC
   ESCHENBACH, DA
   PASTOREK, JG
   WILLIAMS, S
   GIBBS, RS
   CAREY, JC
TI OUTCOME OF THE VAGINAL INFECTIONS AND PREMATURITY STUDY - RESULTS OF A
   CLINICAL-TRIAL OF ERYTHROMYCIN AMONG PREGNANT-WOMEN COLONIZED WITH
   GROUP-B STREPTOCOCCI
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE GROUP B STREPTOCOCCUS; STREPTOCOCCUS AGALACTIAE; LOW BIRTH WEIGHT;
   PRETERM BIRTH; CLINICAL TRIAL
ID SELECTIVE INTRAPARTUM CHEMOPROPHYLAXIS; PLACEBO-CONTROLLED TRIAL;
   CHLAMYDIA-TRACHOMATIS; MEMBRANES; DELIVERY; RUPTURE; DISEASE
AB OBJECTIVE: Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth.
   STUDY DESIGN: in a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy.
   RESULTS: Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance.
   CONCLUSIONS: In this study of pregnant women colonized with group B streptococci Treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.
C1 NIAID, BETHESDA, MD USA.
   COLUMBIA UNIV, DEPT PEDIAT, NEW YORK, NY USA.
   RES TRIANGLE INST, RES TRIANGLE PK, NC 27709 USA.
   UNIV WASHINGTON, DEPT OBSTET & GYNECOL, SEATTLE, WA USA.
   LOUISIANA STATE UNIV, DEPT OBSTET & GYNECOL, NEW ORLEANS, LA 70112 USA.
   UNIV TEXAS, DEPT OBSTET & GYNECOL, SAN ANTONIO, TX USA.
   UNIV OKLAHOMA, DEPT OBSTET & GYNECOL, OKLAHOMA CITY, OK 73190 USA.
RP KLEBANOFF, MA (reprint author), NICHHD, 6100 BLDG, ROOM 7B03, BETHESDA, MD 20892 USA.
FU NIAID NIH HHS [AI-4-2532]; NICHD NIH HHS [HD-3-2832, HD-3-2836]
NR 23
TC 49
Z9 49
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 1995
VL 172
IS 5
BP 1540
EP 1545
DI 10.1016/0002-9378(95)90493-X
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA QZ874
UT WOS:A1995QZ87400030
PM 7755068
ER

PT J
AU SIBAI, BM
   CARITIS, SN
   THOM, E
   SHAW, K
   MCNELLIS, D
AF SIBAI, BM
   CARITIS, SN
   THOM, E
   SHAW, K
   MCNELLIS, D
TI LOW-DOSE ASPIRIN IN NULLIPAROUS WOMEN - SAFETY OF CONTINUOUS EPIDURAL
   BLOCK AND CORRELATION BETWEEN BLEEDING-TIME AND MATERNAL-NEONATAL
   BLEEDING COMPLICATIONS
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE LOW-DOSE ASPIRIN; PREGNANCY; EPIDURAL; BLEEDING TIME
ID FETAL GROWTH-RETARDATION; REGIONAL ANESTHESIA; PREGNANT-WOMEN;
   PREECLAMPSIA; PREVENTION; THROMBOCYTOPENIA; THROMBOXANE
AB OBJECTIVE: Our purpose was to determine the frequency and safety of the use of epidural anesthesia and the correlation between bleeding time and maternal-neonatal bleeding complications in a group of pregnant women who participated in a multicenter trial of low-dose aspirin in pregnancy.
   STUDY DESIGN: Data regarding type of anesthesia used for labor and delivery were available in 1629 nulliparous women who were randomly assigned at 13 to 27 weeks to receive 60 mg/day aspirin or a placebo. A total of 891 (55%) received epidural anesthesia, and the remaining 738 did not.
   RESULTS: Among the 891 women known to have received epidural anesthesia, 451 were assigned to low-dose aspirin and 440 to placebo. There was no instance of bleeding related to epidural use. In addition, there were no differences in maternal and neonatal complications between those receiving or not receiving epidural anesthesia. Within the group receiving epidural anesthesia there were no differences in bleeding complications between those assigned to aspirin on placebo. One of the five centers also obtained bleeding times in 303 women (149 received aspirin and 154 received placebo). The mean +/- SD bleeding time in women assigned to low-dose aspirin was significantly higher than in women assigned to placebo (6.99 +/- 2.95 minutes vs 5.99 +/- 2.43 minutes, p = 0.004). In addition, the frequency of women having a bleeding time > 10 minutes was higher in the aspirin group (14.1% vs 5.2%, p = 0.01). Interestingly, women who received an epidural anesthetic had a lower bleeding time than those not receiving an epidural (p = 0.003), irrespective of the treatment used.
   CONCLUSIONS: In women assigned to low-dose aspirin there were no adverse effects related to epidural anesthesia. In spite of an increased bleeding time in a subset of pregnant women assigned to low-dose aspirin, maternal-neonatal bleeding complications were not increased.
C1 UNIV TENNESSEE,DEPT OBSTET & GYNECOL,MEMPHIS,TN.
   NICHHD,BETHESDA,MD.
OI caritis, steve/0000-0002-2169-0712
FU NICHD NIH HHS [HD 21366, HD 21410, HD 21434]
NR 22
TC 29
Z9 30
U1 0
U2 1
PU MOSBY-YEAR BOOK INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 1995
VL 172
IS 5
BP 1553
EP 1557
DI 10.1016/0002-9378(95)90495-6
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA QZ874
UT WOS:A1995QZ87400032
PM 7755070
ER

PT J
AU HOLLAND, GN
   LEVINSON, RD
   JACOBSON, MA
   CAUSEY, D
   DAVIS, R
   FEINBERG, JE
   HARDY, WD
   HEINEMANN, MH
   KUPPERMANN, BD
   MILLS, J
   ODONNELL, JJ
   POLSKY, B
AF HOLLAND, GN
   LEVINSON, RD
   JACOBSON, MA
   CAUSEY, D
   DAVIS, R
   FEINBERG, JE
   HARDY, WD
   HEINEMANN, MH
   KUPPERMANN, BD
   MILLS, J
   ODONNELL, JJ
   POLSKY, B
TI DOSE-RELATED DIFFERENCE IN PROGRESSION RATES OF CYTOMEGALOVIRUS
   RETINOPATHY DURING FOSCARNET MAINTENANCE THERAPY
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ACQUIRED IMMUNODEFICIENCY SYNDROME; INTRAVENOUS FOSCARNET; VIRUS
   RETINITIS; AIDS
AB PURPOSE: A previous dose ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs.
   METHODS: Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS 90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow up photographs and pre established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups.
   RESULTS: The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 mu m/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 mu m/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 mu m/day; P = .031).
   CONCLUSION: Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.
C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA.
   UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA.
   SAN FRANCISCO GEN HOSP,MED SERV,SAN FRANCISCO,CA 94110.
   UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033.
   HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115.
   NIAID,BETHESDA,MD 20892.
   UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024.
   MEM SLOAN KETTERING CANC CTR,OPHTHALMOL SERV,NEW YORK,NY 10021.
   CORNELL UNIV,COLL MED,NEW YORK,NY.
   UNIV CALIF LOS ANGELES,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90024.
   SAN FRANCISCO GEN HOSP,OPHTHALMOL SERV,SAN FRANCISCO,CA 94110.
   MEM SLOAN KETTERING CANC CTR,INFECT DIS SERV,NEW YORK,NY 10021.
RP HOLLAND, GN (reprint author), UNIV CALIF LOS ANGELES,JULES STEIN EYE INST,CTR OCULAR INFLAMMATORY DIS,100 STEIN PLAZA,LOS ANGELES,CA 90024, USA.
FU NIAID NIH HHS [AI27660-07]
NR 9
TC 17
Z9 17
U1 0
U2 0
PU OPHTHALMIC PUBL CO
PI CHICAGO
PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAY
PY 1995
VL 119
IS 5
BP 576
EP 586
PG 11
WC Ophthalmology
SC Ophthalmology
GA QW578
UT WOS:A1995QW57800004
PM 7733183
ER

PT J
AU MELHEM, MF
   LAW, JC
   ELASHMAWY, L
   JOHNSON, JT
   LANDRENEAU, RJ
   SRIVASTAVA, S
   WHITESIDE, TL
AF MELHEM, MF
   LAW, JC
   ELASHMAWY, L
   JOHNSON, JT
   LANDRENEAU, RJ
   SRIVASTAVA, S
   WHITESIDE, TL
TI ASSESSMENT OF SENSITIVITY AND SPECIFICITY OF IMMUNOHISTOCHEMICAL
   STAINING OF P53 IN LUNG AND HEAD AND NECK CANCERS
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMAS; T-ANTIGEN; PROTEIN;
   MUTATIONS; EXPRESSION; ONCOGENE; FORMS; COMPLEX; CYCLE
AB Thirty-two primary carcinomas of the lung and 17 carcinomas of the head and neck (HN) were systematically analyzed for p53 mutations in the highly conserved regions of the gene (exons 5-8). Frozen sections of the same tumors were stained immunohistochemically to assess the sensitivity and specificity of p53 expression as determined by the presence or absence of the protein. On the basis of histology, the lung tumors studied were divided into adenocarcinomas (AC; n = 15), squamous-cell carcinomas (SCC; n = 12), and large-cell carcinomas (LCC; n = 5). All the NN cancers were SCC. Mutations in the p53 gene were detected by direct sequencing of amplified polymerase chain reaction products in six AC of the lungs (40%), three SCC of the lungs (25%), and one LCC (20%), with an overall mutation frequency of 31%. Nine AC (60%) of the lungs, five SCC (42%), and four LCC (80%) were p53-positive by immunohistochemistry. Among HN cancers, p53 mutations were detected in seven tumors (41%). Nine HN tumors (53%) were positive for p53 Negative staining, despite the presence of p53 mutations, was confined to nonsense mutations with truncated p53 and to single-base mutations not causing any change in the amino acid Although immunohistochemical staining for mutated p53 is sensitive and single to perform as a screening method it is not as specific for evaluation of p53 mutations in lung and HN cancers.
C1 UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA.
   UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HUMAN GENET,PITTSBURGH,PA 15261.
   PITTSBURGH CANC INST,PITTSBURGH,PA 15213.
   UNIV PITTSBURGH,MED CTR,DEPT PATHOL,PITTSBURGH,PA.
   UNIV PITTSBURGH,MED CTR,DEPT OTOLARYNGOL,PITTSBURGH,PA.
   UNIV PITTSBURGH,MED CTR,DEPT SURG,PITTSBURGH,PA.
   NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892.
RP MELHEM, MF (reprint author), VET ADM MED CTR,DEPT PATHOL & LAB MED,UNIV DR C,PITTSBURGH,PA 15240, USA.
FU NCI NIH HHS [N01 CN15393]
NR 42
TC 50
Z9 53
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BALTIMORE
PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAY
PY 1995
VL 146
IS 5
BP 1170
EP 1177
PG 8
WC Pathology
SC Pathology
GA QX871
UT WOS:A1995QX87100017
PM 7747811
ER

PT J
AU SHERER, DM
   HULBERT, WC
AF SHERER, DM
   HULBERT, WC
TI PRENATAL SONOGRAPHIC DIAGNOSIS AND SUBSEQUENT CONSERVATIVE
   SURGICAL-MANAGEMENT OF BILATERAL URETEROCELES
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE URETEROCELES; DUPLICATED URINARY COLLECTING SYSTEMS; SONOGRAPHY
AB Prenatal sonographic diagnosis of ureteroceles usually involves clearly duplicated urinary collecting systems associated with ectopic ureters draining the upper renal moieties. We present an unusual case in which an initial sonographic examination was consistent with bilateral orthotopic ureteroceles in association with bilateral single renal systems. The possibility of single systems raised perinatal considerations unique to this anomaly. Repeat prenatal sonography was suggestive of duplex systems and subsequently confirmed as such by neonatal ultrasound and voiding cystourethrogram. At the age of 1 month, the infant underwent bilateral ipsilateral ureteroureterostomy with conservation of the bilateral dilated upper renal moieties. We discuss the possible pathophysiology underlying the different conflicting sonographic findings and address current management of such lesions.
RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATOL RES BRANCH,WASHINGTON,DC 20007, USA.
NR 0
TC 7
Z9 7
U1 0
U2 0
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 381 PARK AVE SOUTH, NEW YORK, NY 10016
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAY
PY 1995
VL 12
IS 3
BP 174
EP 177
DI 10.1055/s-2007-994445
PG 4
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA QY134
UT WOS:A1995QY13400006
PM 7612089
ER

PT J
AU FUHRER, MJ
AF FUHRER, MJ
TI CONFERENCE REPORT - AN AGENDA FOR MEDICAL REHABILITATION OUTCOMES
   RESEARCH
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Editorial Material
DE OUTCOMES; MEDICAL REHABILITATION; TREATMENT EFFECTIVENESS;
   COST-EFFECTIVENESS
AB On August 29 to 31, 1994, a conference was conducted to develop recommendations for needed initiatives in medical rehabilitation outcomes research.  Organized by the National Center for Medical Rehabilitation Research and cosponsored with the Agency for Health Care Policy and Research, the conference was entitled ''An Agenda for Medical Rehabilitation Outcome Research.''  The resulting recommendations are presented in four areas:  philosophic issues; strategy and design issues; measurement of disability and handicap; and measurement of quality-of-life and of health status.
RP FUHRER, MJ (reprint author), NICHHD,NATL CTR MED REHABIL RES,6100 EXECUT BLDG,ROOM 2A03,BETHESDA,MD 20892, USA.
NR 3
TC 25
Z9 25
U1 0
U2 1
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD MAY-JUN
PY 1995
VL 74
IS 3
BP 243
EP 248
DI 10.1097/00002060-199505000-00013
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA RE372
UT WOS:A1995RE37200013
PM 7779339
ER

PT J
AU LANE, MA
   BALL, SS
   INGRAM, DK
   CUTLER, RG
   ENGEL, J
   READ, V
   ROTH, GS
AF LANE, MA
   BALL, SS
   INGRAM, DK
   CUTLER, RG
   ENGEL, J
   READ, V
   ROTH, GS
TI DIET RESTRICTION IN RHESUS-MONKEYS LOWERS FASTING AND GLUCOSE-STIMULATED
   GLUCOREGULATORY END-POINTS
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE MACACA MULATTA; AGING; CALORIC RESTRICTION; GLUCOSE METABOLISM;
   GLYCATION; DUAL-ENERGY X-RAY ABSORPTIOMETRY
ID AGING PROCESS; INSULIN; RATS; AGE
AB Male rhesus monkeys (Macaca mulatta) of different age groups representing the species life span were fed ad libitum or a 30% reduced calorie diet over a 7-yr period. During the first 2-3 yr of this longitudinal study, glucose and insulin levels were not altered by diet restriction (DR). However, reductions in fasting blood glucose became apparent in DR animals after 3-4 yr. At the end of the 6th yr of study, glycated hemoglobin was measured, and intravenous glucose tolerance tests (IVGTTs) were conducted. Maximum glucose levels reached during IVGTTs increased with age but were lower in DR animals compared with controls. Several measures of the insulin response (baseline, maximum, and integrated areas under curve) increased with age and were lower in DR monkeys. With the exception of glycated hemoglobin, which was not different in monkeys subjected to DR, these findings confirm previous studies in rodents demonstrating that DR alters glucose metabolism and may be related to the antiaging action of this intervention.
C1 NIH, NATL CTR RES RESOURCES, CTR ANIM, PRIMATE UNIT, POOLESVILLE, MD 20837 USA.
   UNIV MISSISSIPPI, SCH MED, DEPT PATHOL, JACKSON, MS 39216 USA.
RP LANE, MA (reprint author), NIA, HOPKINS BAYVIEW MED CTR, NATHAN SHOCK LABS, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA.
NR 32
TC 67
Z9 68
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD MAY
PY 1995
VL 268
IS 5
BP E941
EP E948
PG 8
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA QW584
UT WOS:A1995QW58400020
PM 7762649
ER

PT J
AU GU, ZF
   CORLETO, VD
   MANTEY, SA
   COY, DH
   MATON, PN
   JENSEN, RT
AF GU, ZF
   CORLETO, VD
   MANTEY, SA
   COY, DH
   MATON, PN
   JENSEN, RT
TI SOMATOSTATIN RECEPTOR SUBTYPE 3 MEDIATES THE INHIBITORY-ACTION OF
   SOMATOSTATIN ON GASTRIC SMOOTH-MUSCLE CELLS
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE GASTRIC SMOOTH MUSCLE; G PROTEIN-LINKED RECEPTOR; MUSCLE RELAXATION;
   LIGAND DEGRADATION
ID PITUITARY TUMOR-CELLS; BINDING-SITES; CEREBRAL-CORTEX; RAT; MEMBRANES;
   PEPTIDE; PROTEIN; ENDOPEPTIDASE-24.11; SOLUBILIZATION; RELAXATION
AB Previous functional studies show that somatostatin (SS) interacts with specific receptors to inhibit relaxation in gastric smooth muscle cells. There are no ligand binding studies, and it is unknown which of the five subtypes of SS receptors mediates the action. Dispersed gastric smooth muscle cells from guinea pig bound both (125)-labeled SS-14 and I-125-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (where Nal indicates N-naphthylalanine) (cyclo-SS-8), a synthetic peptidase-resistant octapeptide SS analogue. SS-28 and SS-14, cyclo-SS-8, and SS analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol [SMS-(201-995) (octreotide)] inhibited I-125-cyclo-SS-8 binding with relative potencies of SS-28 = cyclo-SS-8 = SMS-(201-995) (octreotide), and the binding was not affected by the addition of protease inhibitors. SS-14 caused inhibition only in the presence of protease inhibitors. Ligand analysis demonstrated a two-binding-site model. Analysis of the relationship between biological function and binding suggested the high-affinity sites mediated the relaxant action of SS. 5'-Guanylylimidodiphosphate [Gpp(NH)p?] inhibited binding by reducing the affinity of the high-affinity site. Six SS-8 analogues that distinguish SS subtypes showed that I-125-SS-14 bound to somatostatin receptor subtype 3 (SSTR(3)). The results demonstrated that gastric smooth muscle cells possess distinct receptors for SS of the SSTR(3) subtype. Occupation of these sites inhibits relaxation in gastric smooth muscle cells. Modulation between the high- and low-affinity binding states of SSTR(3) is at least partially mediated by activation of guanine nucleotide regulatory proteins.
C1 NIDDKD, DIGEST DIS BRANCH, BETHESDA, MD 20892 USA.
   TULANE UNIV, MED CTR, DEPT MED, PEPTIDE RES LABS, NEW ORLEANS, LA 70112 USA.
NR 39
TC 26
Z9 26
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD MAY
PY 1995
VL 268
IS 5
BP G739
EP G748
PG 10
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA QW835
UT WOS:A1995QW83500003
PM 7762657
ER

PT J
AU HIRUMA, H
   NOGUCHI, CT
   UYESAKA, N
   SCHECHTER, AN
   RODGERS, GP
AF HIRUMA, H
   NOGUCHI, CT
   UYESAKA, N
   SCHECHTER, AN
   RODGERS, GP
TI CONTRIBUTIONS OF SICKLE HEMOGLOBIN POLYMER AND SICKLE-CELL MEMBRANES TO
   IMPAIRED FILTERABILITY
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE RHEOLOGY; PATHOPHYSIOLOGY; THERAPY; BLOOD FLOW; MICROVASCULAR PATHOLOGY
ID RED-BLOOD-CELLS; OXYGEN-TENSION; VISCOELASTIC BEHAVIOR;
   DEOXYHEMOGLOBIN-S; ERYTHROCYTES; DISEASE; DEFORMABILITY; HETEROGENEITY;
   DENSITY; ANEMIA
AB Sickle cell anemia is a disease of abnormal theology caused by acute and reversible, as well as chronic and irreversible, changes in the properties and deformability of sickle erythrocytes. Deformability is determined by several factors, including intracellular sickle hemoglobin polymerization, the abnormal membrane properties of sickle cells, and the abnormal theological properties of the soluble concentrated hemoglobin solution within dense sickle red blood cells. In this study, we used a 5-mu m pore nickel mesh filter to evaluate quantitatively the effects of these factors on the filterability of erythrocytes containing sickle hemoglobin. We used sickle trait and sickle/beta(+)-thalassemia cells, because they have minimal membrane abnormalities or density heterogeneity, to investigate the effects of polymer formation on theological properties. We found that filterability of these cells is sensitive to small amounts of intracellular polymer and that impaired filtration is linearly related to oxygen-dependent polymer formation, up to a polymer fraction of 0.3. By increasing the proportion of dense cells in populations of normal cells or cells from individuals with sickle syndromes and equilibrating these cells with gas ligands, we estimate that polymerization, even at 95% saturation, contributes twice as much to impaired filterability of sickle erythrocytes as the abnormal membranes in homozygous sickle cell disease. At lower saturation values, the effects of polymer are even greater. The viscosity of the concentrated hemoglobin in dense cells had the smallest effect, over physiologically relevant saturation values. These results emphasize the importance of sickle hemoglobin polymerization in the pathogenesis of sickle cell disease and should help define its pathophysiology and responses to therapy in quantitative terms.
C1 NIDDKD, BIOL CHEM LAB, BETHESDA, MD 20892 USA.
   NIPPON MED COLL, DEPT PHYSIOL, TOKYO 113, JAPAN.
NR 33
TC 23
Z9 24
U1 1
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD MAY
PY 1995
VL 268
IS 5
BP H2003
EP H2008
PG 6
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
   Disease
SC Cardiovascular System & Cardiology; Physiology
GA QW850
UT WOS:A1995QW85000028
ER

PT J
AU GEORGE, DT
   LINDQUIST, T
   NUTT, DJ
   RAGAN, PW
   ALIM, T
   MCFARLANE, V
   LEVISS, J
   ECKARDT, MJ
   LINNOILA, M
AF GEORGE, DT
   LINDQUIST, T
   NUTT, DJ
   RAGAN, PW
   ALIM, T
   MCFARLANE, V
   LEVISS, J
   ECKARDT, MJ
   LINNOILA, M
TI EFFECT OF CHLORIDE OR GLUCOSE ON THE INCIDENCE OF LACTATE-INDUCED PANIC
   ATTACKS
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ISOPROTERENOL ANXIETY-STATES; SENSITIVE K+ CHANNELS; NORADRENERGIC
   FUNCTION; BINDING-SITES; DISORDER; HYPOGLYCEMIA; INFUSIONS;
   SULFONYLUREAS; LOCALIZATION; BRAIN
AB Objective: This study was designed to test. the hypothesis that the addition of chloride to a lactate infusion would reduce the frequency of panic attacks. Method: The subjects included 14 healthy volunteers and 20 patients meeting the DSM-IV criteria for panic disorder. All subjects received an infusion of lactate dissolved in 0.9% sodium chloride and an infusion of lactate dissolved in 5% dextrose in water on separate days in a random-order, double-blind procedure. Blood pressure, heart rate, and panic symptoms were measured at 3-minute intervals during the infusions. The occurrence organic attacks was ascertained through the subjects' reports of losing control, panicking, or ''going crazy'' and the presence of at least four Research Diagnostic Criteria symptoms of a panic attack. Results: Fifteen (75%) of the patients with panic disorder reported a panic attack during one of the infusions or both; no healthy volunteers had a panic attack. The patients with panic disorder were significantly more likely to have a panic attack during the lactate/sodium chloride infusion than during the infusion of lactate/5% dextrose in water. The number of panic attack symptoms reported at 3-minute intervals did not differ between the two types of infusion. Conclusions: The coadministration of glucose resulted in a reduced sensitivity to the panicogenic effects of lactate. The hypothesis that adding chloride to the infusion would reduce the frequency of lactate-induced panic attacks was not supported.
C1 NIAAA,OFF SCI DIRECTOR,BETHESDA,MD 20892.
   VET ADM MED CTR,NATL INST DRUG ABUSE RES UNIT,WASHINGTON,DC 20422.
RP GEORGE, DT (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3B19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 41
TC 7
Z9 7
U1 3
U2 3
PU AMER PSYCHIATRIC ASSOCIATION
PI WASHINGTON
PA 1400 K ST NW, WASHINGTON, DC 20005
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD MAY
PY 1995
VL 152
IS 5
BP 692
EP 697
PG 6
WC Psychiatry
SC Psychiatry
GA QV324
UT WOS:A1995QV32400007
PM 7726308
ER

PT J
AU ASHERY, RS
   CARLSON, RG
   FALCK, RS
   SIEGAL, HA
   WANG, JC
AF ASHERY, RS
   CARLSON, RG
   FALCK, RS
   SIEGAL, HA
   WANG, JC
TI FEMALE CONDOM USE AMONG INJECTION DRUG-USING AND CRACK COCAINE-USING
   WOMEN
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Letter
ID PREVENTION; AIDS
C1 WRIGHT STATE UNIV,SCH MED,DEPT COMMUNITY HLTH,DAYTON,OH 45401.
   NATL INST DRUG ABUSE,COMMUNITY RES BRANCH,ROCKVILLE,MD.
FU NIDA NIH HHS [UO1 DAO7305]
NR 10
TC 15
Z9 15
U1 0
U2 0
PU AMER PUBLIC HEALTH ASSN INC
PI WASHINGTON
PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAY
PY 1995
VL 85
IS 5
BP 736
EP 737
DI 10.2105/AJPH.85.5.736
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QW839
UT WOS:A1995QW83900032
PM 7733445
ER

PT J
AU BUSSE, W
   BANKSSCHLEGEL, SP
   LARSEN, GL
AF BUSSE, W
   BANKSSCHLEGEL, SP
   LARSEN, GL
TI CHILDHOOD-ONSET VERSUS ADULT-ONSET ASTHMA
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
ID NORMAL INFANTS; BRONCHIAL HYPERRESPONSIVENESS; INHALANT ALLERGENS;
   AIRWAY REACTIVITY; RISK-FACTORS; CHILDREN; RESPONSIVENESS; DISEASE; IGE;
   ANTIBODIES
C1 NHLBI,DIV LUNG DIS,AIRWAY BIOL & DIS PROGRAM,BETHESDA,MD 20892.
   UNIV WISCONSIN,DEPT MED,DIV CLIN IMMUNOL & ALLERGY,MADISON,WI.
   UNIV COLORADO,SCH MED,NATL JEWISH CTR IMMUNOL & RESP MED,PEDIAT PULM MED SECT,DENVER,CO.
NR 41
TC 53
Z9 53
U1 0
U2 0
PU AMER LUNG ASSOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAY
PY 1995
VL 151
IS 5
BP 1635
EP 1639
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA QX804
UT WOS:A1995QX80400055
PM 7735626
ER

PT J
AU SHARP, DS
   CHYOU, PH
   CURB, JD
AF SHARP, DS
   CHYOU, PH
   CURB, JD
TI FISH CONSUMPTION MAY LIMIT THE DAMAGE OF SMOKING ON THE LUNG
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Letter
C1 HONOLULU HEART PROGRAM,HONOLULU,HI.
RP SHARP, DS (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA.
NR 4
TC 3
Z9 3
U1 0
U2 0
PU AMER LUNG ASSOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAY
PY 1995
VL 151
IS 5
BP 1688
EP 1689
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA QX804
UT WOS:A1995QX80400068
ER

PT J
AU PROSCHAN, MA
   FOLLMANN, DA
AF PROSCHAN, MA
   FOLLMANN, DA
TI MULTIPLE COMPARISONS WITH CONTROL IN A SINGLE EXPERIMENT VERSUS SEPARATE
   EXPERIMENTS - WHY DO WE FEEL DIFFERENTLY
SO AMERICAN STATISTICIAN
LA English
DT Article
DE ASSOCIATION; DISPERSION ORDERING; DUNNETTS PROCEDURE; FAMILYWISE ERROR
   RATE; MIXTURE DISTRIBUTIONS; MULTIPLE COMPARISONS; POWER
AB We contrast comparisons of several treatments to control in a single experiment versus separate experiments in terms of Type I error rate and power. It is shown that if no Dunnett correction is applied in the single experiment case with relatively few treatments, the distribution of the number of Type I errors is not that different from what it would be in separate experiments with the same number of subjects in each treatment. The difference becomes more pronounced with a larger number of treatments. Extreme outcomes (either very few or very many rejections) are more likely when comparisons are made in a single experiment. When the total number of subjects is the same in a single versus separate experiments, power is generally higher in a single experiment even if a Dunnett adjustment is made.
RP PROSCHAN, MA (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA.
NR 9
TC 13
Z9 13
U1 2
U2 4
PU AMER STATIST ASSN
PI ALEXANDRIA
PA 1429 DUKE ST, ALEXANDRIA, VA 22314
SN 0003-1305
J9 AM STAT
JI Am. Stat.
PD MAY
PY 1995
VL 49
IS 2
BP 144
EP 149
DI 10.2307/2684628
PG 6
WC Statistics & Probability
SC Mathematics
GA RN994
UT WOS:A1995RN99400004
ER

PT J
AU CAHNMANN, HJ
AF CAHNMANN, HJ
TI A FAST PHOTOISOMERIZATION METHOD FOR THE PREPARATION OF TRITIUM-LABELED
   9-CIS-RETINOIC ACID OF HIGH SPECIFIC ACTIVITY
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
ID 9-CIS RETINOIC ACID; X-RECEPTOR
AB A method is described by which tritium-labeled all-trans retinoic acid of high specific activity (up to similar to 51 Ci/mmol corresponding to 85% of theoretical) is converted photolytically within a fraction of a second to a mixture of retinoic acid stereoisomers. One of these isomers, 9-cis-retinoic acid, was obtained in high radiochemical purity by reverse-phase HPLC of the stereoisomer mixture. This fast photolysis was obtained by using a high-pressure 100-W mercury lamp operated at 86 +/- 2 W. A copper sulfate solution was used as a light filter to eliminate short-wave ultraviolet radiation as well as much of the infrared radiation. The geometry of the experimental set-up allowed a maximal amount of the light output of the lamp to reach the retinoic acid solution. Reverse-phase HPLC of the photolytically generated retinoic acid stereoisomer mixture provided pure 9-cis-retinoic acid in 4.5% yield after irradiation for 0.6 s. A steady-state equilibrium of retinoic acid stereoisomers was reached when the irradiation time was extended to a total of 4-6 s (10-11% yield of 9-cis retinoic acid). (C) 1995 Academic Press, Inc.
RP CAHNMANN, HJ (reprint author), NIDDK,GENET & BIOCHEM BRANCH,BLDG 10,ROOM 8N315,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 13
TC 5
Z9 5
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 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD MAY 1
PY 1995
VL 227
IS 1
BP 49
EP 53
DI 10.1006/abio.1995.1251
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA QW181
UT WOS:A1995QW18100007
PM 7668391
ER

PT J
AU PHILLIPS, L
   HANSON, R
   BENNET, PH
AF PHILLIPS, L
   HANSON, R
   BENNET, PH
TI STABILITY OF PLASMA-GLUCOSE DURING STORAGE
SO ANNALS OF CLINICAL BIOCHEMISTRY
LA English
DT Letter
RP PHILLIPS, L (reprint author), NIDDKD,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA.
NR 1
TC 1
Z9 1
U1 0
U2 1
PU ROYAL SOC MEDICINE SERVICES LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE
SN 0004-5632
J9 ANN CLIN BIOCHEM
JI Ann. Clin. Biochem.
PD MAY
PY 1995
VL 32
BP 337
EP 337
PN 3
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA QX859
UT WOS:A1995QX85900015
PM 7632043
ER

PT J
AU PLOTZ, PH
   RIDER, LG
   TARGOFF, IN
   RABEN, N
   OHANLON, TP
   MILLER, FW
AF PLOTZ, PH
   RIDER, LG
   TARGOFF, IN
   RABEN, N
   OHANLON, TP
   MILLER, FW
TI MYOSITIS - IMMUNOLOGICAL CONTRIBUTIONS TO UNDERSTANDING CAUSE,
   PATHOGENESIS, AND THERAPY
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Discussion
ID TRANSFER-RNA-SYNTHETASE; IDIOPATHIC INFLAMMATORY MYOPATHIES;
   INCLUSION-BODY MYOSITIS; T-CELL RECEPTOR; INTERSTITIAL LUNG-DISEASE;
   ANTIGEN PM-SCL; D REGION GENES; POLYMYOSITIS-DERMATOMYOSITIS; CONTROLLED
   TRIAL; AUTOANTIBODIES
AB The myositis syndromes, the most common forms of which are polymyositis and dermatomyositis, are defined by idiopathic chronic inflammation in skeletal muscle. Although initially described more than a century ago, these diseases are so rare and heterogeneous that we have only a limited understanding of their causes and treatment. Recently, autoimmune responses to nuclear and cytoplasmic autoantigens that are unique to patients with myositis, the myositis-specific autoantibodies, have proved clinically useful in helping predict signs and symptoms of myositis, immunogenetics, responses to therapy, and prognosis. We summarize this new information on the variety and nature of these autoantibodies, their target epitopes, and their possible use in identifying causes, pathogenetic mechanisms, and better therapies for these increasingly recognized disorders.
RP PLOTZ, PH (reprint author), NIH,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA.
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
NR 88
TC 116
Z9 119
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 1
PY 1995
VL 122
IS 9
BP 715
EP 724
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA QV151
UT WOS:A1995QV15100010
PM 7702234
ER

PT J
AU STONE, LA
   FRANK, JA
   ALBERT, PS
   BASH, C
   SMITH, ME
   MALONI, H
   MCFARLAND, HF
AF STONE, LA
   FRANK, JA
   ALBERT, PS
   BASH, C
   SMITH, ME
   MALONI, H
   MCFARLAND, HF
TI THE EFFECT OF INTERFERON-BETA ON BLOOD-BRAIN-BARRIER DISRUPTIONS
   DEMONSTRATED BY CONTRAST-ENHANCED MAGNETIC-RESONANCE-IMAGING IN
   RELAPSING-REMITTING MULTIPLE-SCLEROSIS
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID LESIONS
AB Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.
C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892.
   NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892.
   NIH,OFF DIRECTOR,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892.
NR 22
TC 241
Z9 245
U1 1
U2 3
PU LITTLE BROWN CO
PI BOSTON
PA 34 BEACON STREET, BOSTON, MA 02108-1493
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAY
PY 1995
VL 37
IS 5
BP 611
EP 619
DI 10.1002/ana.410370511
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA RF069
UT WOS:A1995RF06900010
PM 7755356
ER

PT J
AU PASS, HW
   TEMECK, BK
   KRANDA, K
   STEINBERG, SM
   PASS, HI
AF PASS, HW
   TEMECK, BK
   KRANDA, K
   STEINBERG, SM
   PASS, HI
TI A PHASE-II TRIAL INVESTIGATING PRIMARY IMMUNOCHEMOTHERAPY FOR MALIGNANT
   PLEURAL MESOTHELIOMA AND THE FEASIBILITY OF ADJUVANT IMMUNOCHEMOTHERAPY
   AFTER MAXIMAL CYTOREDUCTION
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 47th Annual Cancer Symposium of the Society-of-Surgical-Oncology
CY MAR 17-20, 1994
CL HOUSTON, TX
SP Soc Surg Oncol
DE MESOTHELIOMA; CISPLATINUM; TAMOXIFEN; INTERFERON; SURGERY
ID CLONOGENIC-ASSAY; CELL-LINE; INTERFERON; CHEMOTHERAPY; AUGMENTATION;
   COMBINATION; CISPLATINUM; XENOGRAFTS; TAMOXIFEN; ALPHA-2
AB Background: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m(2) four times weekly), interferon-alpha (5 mU/m(2) s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination.
   Methods: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery.
   Results: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2), Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival.
   Conclusions: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted.
C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892.
   NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892.
NR 25
TC 36
Z9 37
U1 0
U2 0
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD MAY
PY 1995
VL 2
IS 3
BP 214
EP 220
DI 10.1007/BF02307026
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA QZ071
UT WOS:A1995QZ07100006
PM 7641017
ER

PT J
AU GRUBBS, CJ
   STEELE, VE
   CASEBOLT, T
   JULIANA, MM
   ETO, I
   WHITAKER, LM
   DRAGNEV, KH
   KELLOFF, GJ
   LUBET, RL
AF GRUBBS, CJ
   STEELE, VE
   CASEBOLT, T
   JULIANA, MM
   ETO, I
   WHITAKER, LM
   DRAGNEV, KH
   KELLOFF, GJ
   LUBET, RL
TI CHEMOPREVENTION OF CHEMICALLY-INDUCED MAMMARY CARCINOGENESIS BY
   INDOLE-3-CARBINOL
SO ANTICANCER RESEARCH
LA English
DT Article
DE DIMETHYLBENZANTHRACENE (DMBA); METHYLNITROSOUREA (MNU); MAMMARY GLAND;
   CANCER; CHEMOPREVENTION; INDOLE-3-CARBINOL
ID RAT; INHIBITION; METABOLISM; LIVER; MICE;
   2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; BIOTRANSFORMATION; ENHANCEMENT;
   PREVENTION; ESTRADIOL
AB Indole-3-carbinol, a component of cruciferous vegetables, was evaluated for it efficacy in the prevention of chemically-induced mammary tumors using three different protocols. Because this compound was unstable, it was administered by gavage rather than in the diet. A preliminary dose range study revealed that dose levels of 100 and 50 mg/day, 5x/week, were not toxic to female Sprague-Dawley rats. Initial studies in the DMBA model showed that administering indole-3-carbinol during the initiation and promotion phases were highly effective chemopreventive methods (91-96% reduction in cancer multiplicity). Subsequent studies showed that the administration of indole-3-carbinol only during the initiation phase (7 days prior to until 7 days post DMBA) was also highly effective as a chemopreventive agent. Determination of enzyme levels in the livers of animals treated long-term with indole-3-carbinol showed high levels of induction of various phase I and phase II drug metabolizing enzymes. Finally, indole-3-carbinol when administered both prior to and after MNU (a direct acting carcinogen) caused a significant decrease (65%) in mammary tumor multiplicity. These results support previous studies that indole-3-carbinol can prevent mammary carcinogenesis by direct and indirect acting carcinogens. Therefore, indole-3-carbinol might be a good candidate for chemoprevention of breast cancer in women.
C1 NCI,CHEMOPREVENT INVEST STUDIES BRANCH,BETHESDA,MD 20892.
   CANADA CANC SOC,DIV PEI,CHARLOTTETOWN,PE,CANADA.
   UNIV FLORIDA,DEPT RESOURCES ANIM,GAINESVILLE,FL 32605.
   NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702.
RP GRUBBS, CJ (reprint author), UNIV ALABAMA,DEPT NUTR SCI,1675 UNIV BLVD,318 WEBB BLDG,BIRMINGHAM,AL 35294, USA.
FU NCI NIH HHS [N01-CN-95156-03, CA28103, N01-CN-95156-04]
NR 35
TC 211
Z9 213
U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22,
   ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD MAY-JUN
PY 1995
VL 15
IS 3
BP 709
EP 716
PG 8
WC Oncology
SC Oncology
GA RP348
UT WOS:A1995RP34800011
PM 7645947
ER

PT J
AU ELIOT, HE
   BORNER, MM
   SINHA, BK
AF ELIOT, HE
   BORNER, MM
   SINHA, BK
TI DIFFERENTIAL ONCOGENE EXPRESSION AND SUSCEPTIBILITY TO APOPTOSIS IN THE
   HUMAN LEUKEMIA HL-60 CELL-LINES - IMPLICATIONS FOR ETOPOSIDE RESISTANCE
SO ANTICANCER RESEARCH
LA English
DT Article
DE ONCOGENE EXPRESSION; APOPTOSIS; HUMAN LEUKEMIA HL-60 CELL LINE;
   ETOPOSIDE RESISTANCE
ID C-JUN PROTOONCOGENE; DNA STRAND BREAKS; MULTIDRUG-RESISTANCE;
   P-GLYCOPROTEIN; TUMOR-CELLS; BCL-2; GENE; DAMAGE; DRUG; CAMPTOTHECIN
AB Mechanisms of etoposide (VP-16) resistance have been evaluated in a human promyelocytic leukemia HL60 cell line. HL60 resistant (HL60/AR) cells were selected for resistance with adriamycin and were 250-fold resistant to VP-16. We have found that while a significantly higher (10 to 15-fold more) dose of VP-16 was required to induce similar amounts of SDS-KCI-precipitable DNA-protein complex formation in the resistant cell line, there was no difference in the repair of VP-16-induced DNA damage indicating that differential DNA repair was not involved in VP-16 resistance in HL60 cells. VP-16 treatment significantly inhibited c-myc expression and induced c-jun and c-fos expressions in sensitive cells. In contrast, VP-16 had no effect on c-myc, c-jun or c-fos expressions in resistant cells. The level of bcl2 oncogene was similar in both cell lines; however; treatment with VP-16 resulted in a time-and dose-dependent degradation of the genomic DNA into oligo-sized DNA only in the sensitive cells, indicating that differential expressions of oncogenes (c-myc, c-jun, and c-fos) and susceptibility to apoptosis may play important roles in the sensitivity and resistance to VP-16 in HL60 cells.
C1 NCI,CLIN PHARMACOL BRANCH,MOLEC & BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892.
RI Borner, Markus/B-7583-2011
NR 32
TC 17
Z9 17
U1 1
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22,
   ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD MAY-JUN
PY 1995
VL 15
IS 3
BP 729
EP 733
PG 5
WC Oncology
SC Oncology
GA RP348
UT WOS:A1995RP34800014
PM 7645949
ER

PT J
AU ROSELLI, M
   HITCHCOCK, CL
   MOLINOLO, A
   MILENIC, DE
   COLCHER, D
   MARTIN, EW
   HINKLE, GH
   SCHLOM, J
AF ROSELLI, M
   HITCHCOCK, CL
   MOLINOLO, A
   MILENIC, DE
   COLCHER, D
   MARTIN, EW
   HINKLE, GH
   SCHLOM, J
TI AUTORADIOGRAPHIC EVALUATION OF RADIOLABELED MONOCLONAL-ANTIBODY B72.3
   DISTRIBUTION IN TUMOR AND LYMPH-NODES OF ADENOCARCINOMA PATIENTS
SO ANTICANCER RESEARCH
LA English
DT Article
DE B72.3; AUTORADIOGRAPHY; ADENOCARCINOMA; RADIOIMMUNOGUIDED SURGERY; LYMPH
   NODES
ID COLORECTAL-CANCER; HUMAN-COLON; GLYCOPROTEIN TAG-72; CARCINOEMBRYONIC
   ANTIGEN; CARCINOMA; RADIOIMMUNODETECTION; RADIOIMMUNOTHERAPY;
   IMMUNOSCINTIGRAPHY; COMPLEMENTATION; LOCALIZATION
AB Monoclonal antibody B72.3 recognizes a pancarcinoma antigen termed TAG-72 and is the MAb in ''OncoScint CR/OV''. Patients undergoing surgical resection of primary or metastatic colorectal or breast carcinoma or pseudomyxoma peritonei were injected i.v. with I-125-labeled MAb B72.3. Autoradiography identified the tissue distribution of the injected radiolabeled MAb B72.3. Immunohistochemical straining identified the corresponding spatial distribution of the target antigen, TAG-72. The labeling pattern seen using autoradiography closely matched the pattern that was observed using immunohistochemical techniques. This was especially notable in the mucin-containing compartments of the different tumors. The I-125-B72.3 was also found associated with the neoplastic cells, demonstrating a good penetration and specificity of the radiopharmaceutical through the tumor masses. The regional lymph nodes examined were the only tissues in which autoradiography and immunoperoxidase gave different results. In these specimens, the presence of TAG-72 antigen in the parafollicular area, as shown by immunoperoxidase, contrasted with the silver grain deposition, due to the I-125-B72.3, in germinal centers. These findings suggest differences in the clearance pathways of the TAG-72 antigen and B72.3 MAb.
C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892.
   OHIO STATE UNIV,DEPT PATHOL,COLUMBUS,OH 43210.
   ARTHUR G JAMES CANC HOSP & RES INST,COLUMBUS,OH.
   OHIO STATE UNIV,DEPT SURG,COLUMBUS,OH 43210.
   OHIO STATE UNIV,DEPT NUCL PHARM,COLUMBUS,OH 43210.
RI Martin Jr, Edward/E-3604-2011
NR 38
TC 11
Z9 11
U1 1
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22,
   ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD MAY-JUN
PY 1995
VL 15
IS 3
BP 975
EP 984
PG 10
WC Oncology
SC Oncology
GA RP348
UT WOS:A1995RP34800056
PM 7645989
ER

PT J
AU WALSH, TJ
   GARRETT, K
   FEUERSTEIN, E
   GIRTON, M
   ALLENDE, M
   BACHER, J
   FRANCESCONI, A
   SCHAUFELE, R
   PIZZO, PA
AF WALSH, TJ
   GARRETT, K
   FEUERSTEIN, E
   GIRTON, M
   ALLENDE, M
   BACHER, J
   FRANCESCONI, A
   SCHAUFELE, R
   PIZZO, PA
TI THERAPEUTIC MONITORING OF EXPERIMENTAL INVASIVE PULMONARY ASPERGILLOSIS
   BY ULTRAFAST COMPUTERIZED-TOMOGRAPHY, A NOVEL, NONINVASIVE METHOD FOR
   MEASURING RESPONSES TO ANTIFUNGAL THERAPY
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID AMPHOTERICIN-B; FUNGAL-INFECTIONS; ACUTE-LEUKEMIA; CHEST CT;
   GRANULOCYTOPENIA; DIAGNOSIS; DISEASE
AB Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (UFCT) in persistently granulocytopenic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compared with those measured by conventional chest radiography, histopathological resolution of lesions, and microbiological clearance of Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously, Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continued to progress in untreated controls, whereas lesions in treated rabbits initially increased and then decreased in response to antifungal therapy in a dosage-dependent manner (P less than or equal to 0.05 to P less than or equal to 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiological clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions due to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the groups compared). These findings establish a correlation among UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of organism-mediated tissue injury.
C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892.
   NATL CTR RES RESOURCES,SURG BRANCH,VET RESOURCES PROGRAM,BETHESDA,MD.
RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA.
NR 35
TC 48
Z9 49
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAY
PY 1995
VL 39
IS 5
BP 1065
EP 1069
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA QW019
UT WOS:A1995QW01900008
PM 7625790
ER

PT J
AU GARDELLA, RS
   DELGIUDICE, RA
AF GARDELLA, RS
   DELGIUDICE, RA
TI GROWTH OF MYCOPLASMA-HYORHINIS CULTIVAR-ALPHA ON SEMISYNTHETIC MEDIUM
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID CULTURES
AB Serial passage of Mycoplasma hyorhinis cultivar alpha (formerly noncultivable strains) has been accomplished in modified CMRL-1066 medium with fetal bovine serum. In modified CMRL-1066 liquid medium, cultivar alpha strains grow at a similar rate and to equivalent titers when compared with BTS-7, the type strain of the species. Further experiments with BTS-7 demonstrate that the extent of growth obtained in the semidefined medium was comparable to growth in conventional mycoplasma medium. M. hyorhinis strains, including cultivar alpha strains, grow in serial passage when fetal bovine serum is replaced with bovine serum albumin, palmitic acid, and cholesterol. The results of these studies show that M. hyorhinis cultivar alpha strains are not nutritionally more fastidious than other mycoplasmas but that they are noncultivable on standard mycoplasma media because they are sensitive to high levels of inhibition activity by medium components.
C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,MYCOPLASMA LAB,FREDERICK,MD 21702.
NR 13
TC 6
Z9 7
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171
SN 0099-2240
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD MAY
PY 1995
VL 61
IS 5
BP 1976
EP 1979
PG 4
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA QW184
UT WOS:A1995QW18400047
PM 7646032
ER

PT J
AU LEWIS, EN
   LEVIN, IW
AF LEWIS, EN
   LEVIN, IW
TI REAL-TIME, MIDINFRARED SPECTROSCOPIC IMAGING MICROSCOPY USING
   INDIUM-ANTIMONIDE FOCAL-PLANE ARRAY DETECTION
SO APPLIED SPECTROSCOPY
LA English
DT Note
DE MIDINFRARED SPECTROSCOPY AND MICROSCOPY; CHEMICAL AND BIOLOGICAL
   IMAGING; REAL TIME IMAGING; FOCAL PLANE ARRAY DETECTION; INDIUM
   ANTIMONIDE
AB A different approach toward mid-infrared spectroscopic imaging microscopy is introduced in which instrumentation is designed about an InSb multichannel, focal-plane array detector and a variable-bandpass dielectric filter. The system may be configured for either macroscopic or microscopic applications, and high-fidelity, chemically specific images may be acquired in real time. With the dielectric filter used in this assembly, continuous tuning is provided for the infrared 4000-2320 cm(-1) spectral region with spectral resolutions of approximately 35-18 cm(-1) at the extremes of this wavelength interval. The functioning of the imaging microscope is demonstrated with samples including polystyrene microspheres, preparations of lipids and an amino acid embedded in KBr disks, and a tissue sample derived from a coronal slice of a monkey cerebellum.
RP LEWIS, EN (reprint author), NIDDKD,PHYS CHEM LAB,BETHESDA,MD 20892, USA.
NR 10
TC 49
Z9 49
U1 0
U2 3
PU SOC APPLIED SPECTROSCOPY
PI FREDERICK
PA PO BOX 1438, FREDERICK, MD 21701
SN 0003-7028
J9 APPL SPECTROSC
JI Appl. Spectrosc.
PD MAY
PY 1995
VL 49
IS 5
BP 672
EP 678
DI 10.1366/0003702953964066
PG 7
WC Instruments & Instrumentation; Spectroscopy
SC Instruments & Instrumentation; Spectroscopy
GA QZ569
UT WOS:A1995QZ56900020
ER

PT J
AU KURZHALS, G
   STOLZ, W
   MACIEJEWSKI, W
   KARPATI, S
   MEURER, M
   BREIT, R
AF KURZHALS, G
   STOLZ, W
   MACIEJEWSKI, W
   KARPATI, S
   MEURER, M
   BREIT, R
TI LOCALIZED CICATRICIAL PEMPHIGOID OF THE BRUNSTING-PERRY TYPE WITH
   TRANSITION INTO DISSEMINATED CICATRICIAL PEMPHIGOID - REPORT OF A CASE
   PROVED BY PREEMBEDDING IMMUNOGOLD ELECTRON-MICROSCOPY
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; CUTANEOUS BASEMENT-MEMBRANE;
   IMMUNOELECTRON MICROSCOPY; ANTIGEN; IMMUNOFLUORESCENT; PROTEIN; IGG;
   AUTOANTIBODIES; DISEASES; INVIVO
AB Background: In 1979, Provost described two patients with the clinical features of disseminated cicatricial pemphigoid for the first time. Until now, only four additional cases of disseminated cicatricial pemphigoid have been described. Existence of diagnosis of disseminated cicatricial pemphigoid has been discussed controversially because in four cases investigated by electron microscopy the blister formation was found below the lamina densa, which is indicative of an epidermolysis bullosa acquisita.
   Observation: A 78-year-old woman is presented with a generalized eruption of blisters leaving behind scars that developed after a 7-year-long history of mild circumscribed recurrent blisters and scarring eruptions that had been diagnosed previously as Brunsting-Perry type of cicatricial pemphigoid. Immunofluorescence antigen mapping disclosed the blister formation above the lamina densa. Electron and immunoelectron microscopy using a preembedding immunogold technique revealed blister formation and antibody binding within the lamina lucida, predominantly below the subbasal dense plate.
   Conclusions: The clinical features of disseminated blistering followed by scarring, the immunofluorescence antigen mapping, and the electron and immunoelectron microscopic findings in our case for the first time clearly prove the existence of a disseminated cicatricial pemphigoid.
C1 CITY HOSP,DEPT DERMATOL & ALLERGOL,MUNICH,GERMANY.
   UNIV MUNICH,DEPT DERMATOL,W-8000 MUNICH,GERMANY.
   NCI,DERMATOL BRANCH,BETHESDA,MD 20892.
NR 58
TC 16
Z9 16
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAY
PY 1995
VL 131
IS 5
BP 580
EP 585
DI 10.1001/archderm.131.5.580
PG 6
WC Dermatology
SC Dermatology
GA QX868
UT WOS:A1995QX86800010
PM 7741546
ER

PT J
AU BORRADORI, L
   CALDWELL, JB
   BRIGGAMAN, RA
   BURR, CE
   GAMMON, WR
   JAMES, WD
   YANCEY, KB
AF BORRADORI, L
   CALDWELL, JB
   BRIGGAMAN, RA
   BURR, CE
   GAMMON, WR
   JAMES, WD
   YANCEY, KB
TI PASSIVE TRANSFER OF AUTOANTIBODIES FROM A PATIENT WITH MUTILATING
   EPIDERMOLYSIS-BULLOSA ACQUISITA INDUCES SPECIFIC ALTERATIONS IN THE SKIN
   OF NEONATAL MICE
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID CUTANEOUS BASEMENT-MEMBRANE; VII COLLAGEN; IMMUNE-COMPLEXES;
   CYCLOSPORINE; COMPONENT; ANTIGEN; IMMUNOFLUORESCENCE; IDENTIFICATION;
   COMPLEMENT; GENE
AB Background: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease.
   Observations: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride-separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice.
   Conclusions: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.
C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892.
   WALTER REED ARMY MED CTR,DERMATOL SERV,WASHINGTON,DC 20307.
   UNIV N CAROLINA,DEPT DERMATOL,CHAPEL HILL,NC 27514.
   UNIFORMED SERV UNIV HLTH SCI,CTR AUDIOVISUAL,BETHESDA,MD 20814.
NR 29
TC 35
Z9 36
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAY
PY 1995
VL 131
IS 5
BP 590
EP 595
DI 10.1001/archderm.131.5.590
PG 6
WC Dermatology
SC Dermatology
GA QX868
UT WOS:A1995QX86800012
PM 7741548
ER

PT J
AU WINOKUR, G
   CORYELL, W
   KELLER, M
   ENDICOTT, J
   LEON, A
AF WINOKUR, G
   CORYELL, W
   KELLER, M
   ENDICOTT, J
   LEON, A
TI A FAMILY STUDY OF MANIC-DEPRESSIVE (BIPOLAR-I) DISEASE - IS IT A
   DISTINCT ILLNESS SEPARABLE FROM PRIMARY UNIPOLAR DEPRESSION
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID AFFECTIVE-DISORDERS; RELATIVES; DIAGNOSIS; SCHIZOPHRENIA; RELIABILITY
AB Objective: To determine whether bipolar I illness is autonomous or part of a multifactorial continuum with unipolar depression. In this study, we compare familial bipolar I illness and depression among three groups: probands with bipolar I disorder; probands with primary unipolar disorder; and controls. We also examine a continuum of severity between psychotic and nonpsychotic patients with bipolar I disorder. Considerable data suggest that bipolar I illness is distinct from unipolar illness as regards epidemiology, familial psychiatric illness, course, response to treatment, and biologic findings.
   Method: Probands were separated into bipolar I and primary unipolar depressive groups. Personally interviewed family members of these patients were compared on variables of bipolar illness or schizoaffective mania and unipolar or schizoaffective depression. A personally examined control group was compared with the relatives of the two proband groups. Similar analyses were performed using data obtained by a systematic family history method. For the same familial variables, psychotic and nonpsychotic manic probands were compared.
   Result: Familial mania is more frequent in families of patients with bipolar disease than in controls or in families of patients with primary unipolar disorder. The latter mio groups did not differ in amount of mania. Unipolar depressive illness or schizoaffective depression was higher in families of probands with bipolar and unipolar disorder than in controls. Probands with bipolar disease separated into those who had psychotic symptoms (including schizoaffective mania) and no psychotic symptoms did not differ from each other in risk for familial mania or depression.
   Conclusions: Bipolar I illness is a separate illness from primary unipolar illness because of an increase in familial mania. Patients with primary unipolar disease and controls show the same amount of familial mania. Lack of an increase in familial illness according to the severity of bipolar disease is against an affective continuum.
C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD 20892.
FU NIMH NIH HHS [R01 MH025478]
NR 26
TC 71
Z9 72
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD MAY
PY 1995
VL 52
IS 5
BP 367
EP 373
PG 7
WC Psychiatry
SC Psychiatry
GA QX404
UT WOS:A1995QX40400004
PM 7726717
ER

PT J
AU CHAN, CC
   ROBERGE, FG
   WHITCUP, SM
   NUSSENBLATT, RB
AF CHAN, CC
   ROBERGE, FG
   WHITCUP, SM
   NUSSENBLATT, RB
TI 32 CASES OF SYMPATHETIC OPHTHALMIA - A RETROSPECTIVE STUDY AT THE
   NATIONAL-EYE-INSTITUTE, BETHESDA, MD, FROM 1982 TO 1992
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ELECTRON-MICROSCOPY; UVEITIS; PROTEIN
AB Objective: To examine the relationship between visual outcome and the clinical management of patients with sympathetic ophthalmia.
   Methods: Thirty-two patients with sympathetic ophthalmia who were seen at the National Eye Institute, Bethesda, Md, between 1982 and 1992, were retrospectively reviewed.
   Results: There were equal numbers of males and females. Sympathetic ophthalmia occurred after trauma in 23 patients and surgery in nine patients. Sixteen of the 32 patients had a final visual acuity of 20/40 or better; 10 patients had a visual acuity worse than 20/200. Good visual outcome was associated with early and aggressive treatment with corticosteroids, sometimes in combination with other immunosuppressive agents. Poor visual acuity was associated with glaucoma, chorioretinal scars in the macula, and persistent uncontrolled inflammation.
   Conclusion: Prompt and aggressive use of antiinflammatory therapy can improve the visual outcome of patients with sympathetic ophthalmia.
C1 NEI,CLIN 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 25
TC 55
Z9 58
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAY
PY 1995
VL 113
IS 5
BP 597
EP 600
PG 4
WC Ophthalmology
SC Ophthalmology
GA QY407
UT WOS:A1995QY40700021
PM 7748129
ER

PT J
AU LIVINGSTON, RA
   HUTTON, N
   HALSEY, NA
   KLINE, RL
   JOYNER, M
   QUINN, TC
AF LIVINGSTON, RA
   HUTTON, N
   HALSEY, NA
   KLINE, RL
   JOYNER, M
   QUINN, TC
TI HUMAN-IMMUNODEFICIENCY-VIRUS SPECIFIC IGA IN INFANTS BORN TO
   HUMAN-IMMUNODEFICIENCY-VIRUS SEROPOSITIVE WOMEN
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID PERINATAL HIV-INFECTION; EARLY DIAGNOSIS; P24 ANTIGEN; ANTIBODIES;
   MOTHERS; UTILITY; TYPE-1; ASSAY
AB Objective: To determine the sensitivity and specificity of human immunodeficiency virus (HIV)-specific IgA for vertically transmitted HIV infection, particularly during the first month of life.
   Design/Setting/Patients: Prospective cohort study of 140 infants born to HIV-seropositive women in a large urban teaching hospital and of 248 older infants and children referred for diagnosis and treatment of HIV infection.
   Main Outcome Measures: The HIV-specific IgA immunoblot results were compared with the infection status of patients as determined by Centers for Disease Control and Prevention (Atlanta, Ga) criteria or by sequential early diagnostic assays for HIV. Sensitivity, specificity, and predictive values were calculated for each age range.
   Results: Among infants studied from birth, the rate of vertical transmission of HIV was 21.6% (25/116). The sensitivity of HIV-specific IgA for the first month of life was 8.0% (2/25), and the specificity was 90.1% (82/91). Sensitivity increased progressively during the first year of life, and the negative predictive value was 94.6% by 6 to 8 months of age. The positive predictive value of this assay was 18.2% for neonates but was 96% to 100% after the first month of life.
   Conclusions: False-positive test results for HIV-specific IgA occurred with diminishing frequency during the first 4 weeks of life, and the frequency of detectable HIV-specific IgA was similar among the HIV-infected and uninfected groups at this age. Beyond 1 month of age, detection of HIV-specific IgA is highly specific and is a useful serum-based assay for early diagnosis of HIV infection. These results suggest that maternal-fetal transfusion is common and support the hypothesis that the majority of maternal-fetal transmission of HIV occurs around the time of parturition.
C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205.
   JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD.
   NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892.
FU NCRR NIH HHS [RR-00052]; NIAID NIH HHS [UO1-AI27565, R01-AI32468]
NR 28
TC 10
Z9 11
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD MAY
PY 1995
VL 149
IS 5
BP 503
EP 507
PG 5
WC Pediatrics
SC Pediatrics
GA QW848
UT WOS:A1995QW84800004
PM 7735402
ER

PT J
AU SNELLER, MC
   HOFFMAN, GS
   TALARWILLIAMS, C
   KERR, GS
   HALLAHAN, CW
   FAUCI, AS
AF SNELLER, MC
   HOFFMAN, GS
   TALARWILLIAMS, C
   KERR, GS
   HALLAHAN, CW
   FAUCI, AS
TI AN ANALYSIS OF 42 WEGENERS GRANULOMATOSIS PATIENTS TREATED WITH
   METHOTREXATE AND PREDNISONE
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID LOW-DOSE METHOTREXATE; PNEUMOCYSTIS-CARINII PNEUMONIA;
   RHEUMATOID-ARTHRITIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; THERAPY;
   PANCYTOPENIA; TRIAL
AB Objective. To determine the efficacy of low-dose methotrexate (MTX) plus prednisone in the treatment of Wegener's granulomatosis (WG).
   Methods. An open-label study of weekly low-dose MTX plus prednisone for the treatment of WG was performed. Forty-two patients who did not have immediately life-threatening disease were enrolled into the study. Outcome was determined by clinical characteristics and pathologic, laboratory, and radiographic findings.
   Results. Weekly administration of MTX and prednisone resulted in remission of disease in 30 of the 42 patients (71%). The median time to remission was 4.2 months, The estimated median time to relapse for all patients in whom remission was achieved was 29 months. Eight patients who had relapses were treated with a second course of MTX plus prednisone, and a second remission was induced in 6 of the 8 (75%).
   Conclusion. Weekly low-dose MTX was shown in this study to be an acceptable alternative form of therapy for selected patients with WG who do not have immediately life-threatening disease or who have developed serious cyclophosphamide-associated toxicity.
RP SNELLER, MC (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA.
NR 25
TC 211
Z9 215
U1 0
U2 0
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD MAY
PY 1995
VL 38
IS 5
BP 608
EP 613
DI 10.1002/art.1780380505
PG 6
WC Rheumatology
SC Rheumatology
GA QX392
UT WOS:A1995QX39200004
PM 7748215
ER

PT J
AU BARRON, KS
   REVEILLE, JD
   CARRINGTON, M
   MANN, DL
   ROBINSON, MA
AF BARRON, KS
   REVEILLE, JD
   CARRINGTON, M
   MANN, DL
   ROBINSON, MA
TI SUSCEPTIBILITY TO REITERS-SYNDROME IS ASSOCIATED WITH ALLELES OF TAP
   GENES
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY COMPLEX; DEPENDENT
   DIABETES-MELLITUS; PROTEASOME-RELATED GENE; MHC-LINKED TRANSPORTER;
   ANTIGEN PRESENTATION; POLYMORPHISM; HAPLOTYPES; POLYMERASE; MOLECULE
AB Objective, Although HLA-B27 is strongly associated with susceptibility to Reiter's syndrome (RS), recent data suggest that an additional modifying or susceptibility gene(s) acts in concert with HLA-B27 to contribute to disease pathogenesis. The recently described TAP genes (transporters associated with antigen processing) are potential candidates because they are polymorphic and their function is to transport antigenic peptides to be loaded in HLA class I molecules,
   Methods. TAP1 and TAP2 alleles were determined for 34 patients with RS (28 HLA-B27 positive, 6 HLA-B27 negative), and their frequencies were compared with those observed for 52 HLA-B27 positive and 80 random disease-free control subjects,
   Results. The allele frequency of TAP1C was greater in patients with RS (8 of 62, 13%) than in random controls (5 of 160, 3%) (P = 0.009), The frequency of TAP2A was greater in RS patients (51 of 66, 77%) than in random controls (88 of 160, 55%) (P = 0.002); likewise, the frequency was greater in HLA-B27 positive RS patients (41 of 54, 76%) than in HLA-B27 positive disease-free controls (49 of 94, 52%) (P = 0.004). Furthermore, the TAP2A allele was present in all RS patients (100%), whereas TAP2A was present in 79% (63 of 80) of the random controls (P = 0.003),
   Conclusion. The association observed between TAP alleles and RS is independent of the presence of HLA-B27, and despite the physical proximity of TAP and HLA class II genes, linkage disequilibrium does not account for the observed associations between TAP and RS, Thus, TAP genes are genetically separated but functionally linked to class I genes, and both contribute to susceptibility to RS.
C1 UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX.
   PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD.
   NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD.
RP BARRON, KS (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK II FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA.
NR 37
TC 43
Z9 44
U1 0
U2 2
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD MAY
PY 1995
VL 38
IS 5
BP 684
EP 689
DI 10.1002/art.1780380517
PG 6
WC Rheumatology
SC Rheumatology
GA QX392
UT WOS:A1995QX39200016
PM 7748224
ER

PT J
AU CHERNY, SS
   FULKER, DW
   HU, S
   PATTATUCCI, AML
   PATTERSON, C
   HAMER, DH
AF CHERNY, SS
   FULKER, DW
   HU, S
   PATTATUCCI, AML
   PATTERSON, C
   HAMER, DH
TI MULTIPOINT INTERVAL MAPPING OF A QUANTITATIVE TRAIT LOCUS FOR SEXUAL
   ORIENTATION USING SELECTED SIB PAIRS
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
C1 UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80309.
   NCI,BIOCHEM LAB,BETHESDA,MD 20892.
RI Cherny, Stacey/B-3315-2008
OI Cherny, Stacey/0000-0002-0269-3352
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PLENUM PUBL CORP
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD MAY
PY 1995
VL 25
IS 3
BP 259
EP 260
PG 2
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA QY385
UT WOS:A1995QY38500032
ER

PT J
AU LIN, N
   EISEN, S
   SCHERRER, J
   GOLDBERG, J
   FABSITZ, R
   TRUE, W
   LYONS, M
AF LIN, N
   EISEN, S
   SCHERRER, J
   GOLDBERG, J
   FABSITZ, R
   TRUE, W
   LYONS, M
TI THE ASSOCIATION BETWEEN MODERATE ALCOHOL-CONSUMPTION AND SYMPTOMS OF
   DEPRESSION - A STUDY OF 475 IDENTICAL, MIDDLE-AGED, MALE TWIN PAIRS
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
C1 WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110.
   VET ADM MED CTR,ST LOUIS,MO 63106.
   ST LOUIS UNIV,SCH PUBL HLTH,ST LOUIS,MO 63108.
   UNIV ILLINOIS,SCH PUBL HLTH,CHICAGO,IL 60680.
   EDWARD HINES VET ADM MED CTR,HINES,IL 60141.
   NHLBI,BETHESDA,MD 20892.
   BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215.
   VET ADM MED CTR,BROCKTON,MA 02401.
RI Lyons, Michael/B-6119-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PLENUM PUBL CORP
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD MAY
PY 1995
VL 25
IS 3
BP 274
EP 275
PG 2
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA QY385
UT WOS:A1995QY38500092
ER

PT J
AU HOHMANN, AA
AF HOHMANN, AA
TI CAN HEALTH-SERVICES RESEARCH HAVE A ROLE IN MANAGED CARE
SO BEHAVIORAL HEALTHCARE TOMORROW
LA English
DT Article
RP HOHMANN, AA (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,SERV RES BRANCH,ROCKVILLE,MD 20857, USA.
NR 4
TC 3
Z9 3
U1 0
U2 0
PU CENTRALINK
PI TIBURON
PA 1110 MAR WEST ST STE E, TIBURON, CA 94920-1879
SN 1063-8490
J9 BEHAV HEALTHC TOM
JI Behav. Healthcare Tomorrow
PD MAY-JUN
PY 1995
VL 4
IS 3
BP 40
EP &
PG 0
WC Psychology, Clinical; Health Policy & Services
SC Psychology; Health Care Sciences & Services
GA RC312
UT WOS:A1995RC31200006
PM 10143417
ER

PT J
AU DAS, PC
   DEY, CD
   SRIDHAR, R
   BISWAS, SK
   DAS, KP
   DASGUPTA, S
AF DAS, PC
   DEY, CD
   SRIDHAR, R
   BISWAS, SK
   DAS, KP
   DASGUPTA, S
TI CONTRACEPTIVE STEROIDS ALTER AMINO-ACID NEUROTRANSMITTER LEVELS IN THE
   RAT-BRAIN
SO BIOCHEMICAL ARCHIVES
LA English
DT Article
ID PITUITARY GONADOTROPIN-SECRETION; OVARIECTOMIZED RATS;
   HORMONE-SECRETION; INDUCED LH; NEURONS; PROGESTERONE; ESTROGEN; SURGE;
   GLUTAMATE; RELEASE
AB Administration of contraceptive steroid ovral(R) to female rats altered the concentration of glycine in midbrain-thalamus-subthalamus and hypothalamus; aspartate in hypothalamus and striatum-hippocampus; and glutamate in cerebellum, hypothalamus, striatum-hippocampus and midbrain-thalamus-subthalamus. Simultaneous alteration of Delta(5)-3 beta-hydroxysteroid dehydrogenase activity in the ovary and adrenal of the rat was also observed after ovral(R) administration. This may indicate the involvement of amino acid neurotransmitters of the central nervous system in modulation of gonadotrophin release to inhibit ovulation.
C1 UNIV CALCUTTA,COLL SCI & TECHNOL,DEPT PHYSIOL,CALCUTTA 700009,W BENGAL,INDIA.
   HOWARD UNIV,CTR CANC,DEPT RADIAT THERAPY,WASHINGTON,DC 20060.
RP DAS, PC (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU MBR PRESS INC
PI KENYON
PA PO BOX P, KENYON, MN 55946-000P
SN 0749-5331
J9 BIOCHEM ARCH
JI Biochem. Arch.
PD MAY
PY 1995
VL 11
IS 2
BP 79
EP 85
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QZ896
UT WOS:A1995QZ89600005
ER

PT J
AU KEON, CA
   TUSCHIYA, N
   KASHIWAYA, Y
   SATO, K
   CLARKE, K
   RADDA, GK
   VEECH, RL
AF KEON, CA
   TUSCHIYA, N
   KASHIWAYA, Y
   SATO, K
   CLARKE, K
   RADDA, GK
   VEECH, RL
TI SUBSTRATE DEPENDENCE OF THE MITOCHONDRIAL ENERGY STATUS IN THE ISOLATED
   WORKING RAT-HEART
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article; Proceedings Paper
CT 653rd Meeting of the Biochemical-Society-of-London
CY SEP 13-16, 1994
CL UNIV SUSSEX, BRIGHTON, ENGLAND
SP Biochem Soc London
HO UNIV SUSSEX
C1 NIAAA,MET LAB,ROCKVILLE,MD.
RP KEON, CA (reprint author), UNIV OXFORD,DEPT BIOCHEM,OXFORD,ENGLAND.
NR 3
TC 2
Z9 2
U1 0
U2 1
PU PORTLAND PRESS
PI LONDON
PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ
SN 0300-5127
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD MAY
PY 1995
VL 23
IS 2
BP S307
EP S307
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA RE085
UT WOS:A1995RE08500200
PM 7672336
ER

PT J
AU MAO, Y
   ZANG, L
   SHI, XL
AF MAO, Y
   ZANG, L
   SHI, XL
TI SINGLET OXYGEN GENERATION IN THE SUPEROXIDE REACTION
SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL
LA English
DT Article
ID HYDROGEN-PEROXIDE; HYDROXYL RADICALS; DNA; MECHANISM; COMPLEX; ION
AB ESR spin trapping was utilized to study the singlet oxygen (O-1(2)) generation in the reaction of superoxide (O-2) with H2O2. The spin trap used was 2,2,6,6-tetramethyl-4-piperdone. Incubation of xanthine, xanthine oxidase and H2O2 generated O-1(2) spin adduct signal. Omission of xanthine, xanthine oxidase or H2O2 caused a sharp decrease in O-1(2) generation. O-1(2) scavenger, sodium azide, inhibited O-1(2) generation while (OH)-O-. scavenger, ethanol, only slightly decreased the sig?al intensity. Potassium superoxide (KO2) decomposition generated O-1(2). Catalase and sodium azide inhibited O-1(2) generation and H2O2 enhanced it. The results demonstrate that O-2 is capable of generating O-1(2) upon reaction with H2O2.
C1 NIH,NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892.
   MONTANA STATE UNIV,DEPT CHEM,BOZEMAN,MT 59717.
RI Shi, Xianglin/B-8588-2012
NR 15
TC 28
Z9 28
U1 1
U2 5
PU ACADEMIC PRESS AUST
PI MARRICKVILLE
PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA
SN 1039-9712
J9 BIOCHEM MOL BIOL INT
JI Biochem. Mol. Biol. Int.
PD MAY
PY 1995
VL 36
IS 1
BP 227
EP 232
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA TB489
UT WOS:A1995TB48900026
PM 7663419
ER

PT J
AU JACOBSON, KA
   FISCHER, B
   JI, XD
AF JACOBSON, KA
   FISCHER, B
   JI, XD
TI CLEAVABLE TRIFUNCTIONAL APPROACH TO RECEPTOR AFFINITY LABELING -
   CHEMICAL REGENERATION OF BINDING TO A(1)-ADENOSINE RECEPTORS
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID ADENOSINE RECEPTORS; IRREVERSIBLE INHIBITORS; A1-ADENOSINE; ANTAGONIST;
   PROTEINS; LIGANDS; REAGENT; DESIGN; A1
AB A general approach for reversible affinity labeling of receptors has been developed. The objective is to carry out a series of chemical modifications resulting in a covalently-modified, yet functionally-regenerated, receptor protein that also may contain a reporter group. The ligand recognition site of Al-adenosine receptors in bovine brain membranes was probed to demonstrate the feasibility of this approach. Use of disulfide or ester linkages, intended for cleavage by exposure of the labeled receptor to either reducing reagents or hydroxylamine, respectively, was considered. Binding of the antagonist radioligand [H-3]CPX was preserved following incubation of the native receptor with 3 M hydroxylamine, while binding was inhibited by the reducing reagent dithiothreitol (DTT) with an IC50 of 0.29 M. Hydroxylamine displaced specific agonist ([H-3]PIA) binding in a noncovalent manner. Specific affinity labels containing reactive isothiocyanate groups were synthesized from XCC (8-[4-[(carboxymethyl)-oxy]-phenyl]-1,3-dipropylxanthine) and shown to bind irreversibly to A(1)-receptors. The ligands were structurally similar to previously reported xanthine inhibitors (e.g., DITC-XAC: (1989) J. Med. Chem. 32, 1043) except that either a disulfide linkage or an ester linkage was incorporated in the chain between the pharmacophore and the isothiocyanate-substituted ring. These groups were intended for chemical cleavage by thiols or hydroxylamine, respectively. Radioligand binding to A(1)-receptors was inhibited by these reactive xanthines in a manner that was not reversed by repeated washing. Hydroxylamine or DTT restored a significant fraction of the binding of [H-3]CPX in A(1)-receptors inhibited by the appropriate cleavable xanthine isothiocyanate derivative.
RP NIDDK, BIOORGAN CHEM LAB, MOLEC RECOGNIT SECT, BLDG 8A, RM B1A-17, BETHESDA, MD 20892 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z01 DK031115-24, Z01 DK031117-20, Z99 DK999999]
NR 24
TC 22
Z9 22
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD MAY-JUN
PY 1995
VL 6
IS 3
BP 255
EP 263
DI 10.1021/bc00033a004
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA RA630
UT WOS:A1995RA63000004
PM 7632796
ER

PT J
AU IVANOV, B
   GRZESIK, W
   ROBEY, FA
AF IVANOV, B
   GRZESIK, W
   ROBEY, FA
TI SYNTHESIS AND USE OF A NEW BROMOACETYL-DERIVATIZED HETEROTRIFUNCTIONAL
   AMINO-ACID FOR CONJUGATION OF CYCLIC RGD-CONTAINING PEPTIDES DERIVED
   FROM HUMAN BONE SIALOPROTEIN
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID NEISSERIA-MENINGITIDIS; AUTOMATED SYNTHESIS; PROTEIN; SEQUENCE;
   ADHESION; POLYMERS
AB A new amino acid derivative, N-alpha-(tert-butyloxycarbonyl)-N-beta-(bromoacetyl)diaminopropionic acid (BBDap), has been synthesized as a reagent for introducing side-chain bromoacetyl groups into any position of a peptide sequence during solid-phase peptide synthesis. By using minor modifications to the protocol of the automated peptide synthesizer and a two-step in situ neutralization procedure, the syntheses of (bromoacetyl)diaminopropionic acid (BDap) in Arg-Gly-Asp-containing peptides from human bone. sialoprotein were optimized and completed. Following HPLC purification, the BDap-derivatized peptides were cyclized or/and conjugated to carrier protein or to glass cover slips. In addition, a new procedure for site-specific conjugation of cyclic peptides to protein carriers or to glass was developed. The cell attachment activity of the peptide derivatives and conjugates was tested in cell adhesion assays with human osteoblasts, and the specificity of the binding was confirmed by competition with linear and/or cyclic forms of GRGDS. The results show that conjugates containing the linear and cyclic derivatives of the peptide EPRGDNYR supported cell attachment and spreading in a dose-dependent manner when the peptides were immobilized as described. Cell attachment to the intact bone sialoprotein and to conjugates containing the linear peptides was abolished by competition with linear and cyclic RGD-containing peptides, whereas the attachment to conjugates containing the cyclic peptide was inhibited only partially, and the cell spreading was preserved even in the presence of RGD-peptides.
C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892.
RP IVANOV, B (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,PEPTIDE & IMMUNOCHEM UNIT,BETHESDA,MD 20892, USA.
NR 25
TC 23
Z9 25
U1 2
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA PO BOX 57136, WASHINGTON, DC 20037-0136
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD MAY-JUN
PY 1995
VL 6
IS 3
BP 269
EP 277
DI 10.1021/bc00033a006
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA RA630
UT WOS:A1995RA63000006
PM 7632798
ER

PT J
AU BAHRO, M
   CANTILLON, M
   RIEMANN, D
   BERGER, M
   STADTMULLER, G
   LIS, S
   KRIEGER, S
AF BAHRO, M
   CANTILLON, M
   RIEMANN, D
   BERGER, M
   STADTMULLER, G
   LIS, S
   KRIEGER, S
TI P300 IN THE DIFFERENTIATION OF ALZHEIMERS-DISEASE AND DEPRESSION
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892.
   UNIV FREIBURG,PSYCHIAT CLIN,FREIBURG,GERMANY.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 1
PY 1995
VL 37
IS 9
BP 596
EP 597
DI 10.1016/0006-3223(95)94426-W
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700017
ER

PT J
AU CALLAHAN, AM
   FRYE, MA
   MARANGELL, LB
   GEORGE, MS
   KETTER, TA
   KIMBRELL, TA
   LHERROU, T
   PAZZAGLIA, PJ
   POST, RM
AF CALLAHAN, AM
   FRYE, MA
   MARANGELL, LB
   GEORGE, MS
   KETTER, TA
   KIMBRELL, TA
   LHERROU, T
   PAZZAGLIA, PJ
   POST, RM
TI DIFFERENTIAL MOOD AND ENDOCRINE EFFECTS OF INTRAVENOUS VS INTRATHECAL
   TRH
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 609
EP 609
DI 10.1016/0006-3223(95)94474-B
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700065
ER

PT J
AU FRYE, MA
   MATHE, AA
   GEORGE, MS
   PAZZAGLIA, PJ
   JERRELS, S
   POST, RM
AF FRYE, MA
   MATHE, AA
   GEORGE, MS
   PAZZAGLIA, PJ
   JERRELS, S
   POST, RM
TI CSF NEUROPEPTIDE-Y IN MOOD DISORDERS AND TREATMENT WITH CARBAMAZEPINE
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
   KAROLINSKA INST,DEPT CLIN NEUROSCI,STOCKHOLM,SWEDEN.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 609
EP 610
DI 10.1016/0006-3223(95)94475-C
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700066
ER

PT J
AU GEORGE, MS
   MATHE, AA
   FRYE, MA
   DAVIS, CL
   PAZZAGLIA, PJ
   RUBINOW, DL
   JERRELS, S
   POST, RM
AF GEORGE, MS
   MATHE, AA
   FRYE, MA
   DAVIS, CL
   PAZZAGLIA, PJ
   RUBINOW, DL
   JERRELS, S
   POST, RM
TI CSF CGRP CORRELATES WITH NEUROPEPTIDES IN CONTROLS BUT NOT
   AFFECTIVE-ILLNESS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
   KAROLINSKA INST,STOCKHOLM,SWEDEN.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 610
EP 610
DI 10.1016/0006-3223(95)94476-D
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700067
ER

PT J
AU KIMBRELL, TA
   GEORGE, MS
   PAREKH, PI
   KETTER, TA
   HERSCOVITCH, P
   POST, RM
AF KIMBRELL, TA
   GEORGE, MS
   PAREKH, PI
   KETTER, TA
   HERSCOVITCH, P
   POST, RM
TI REGIONAL BRAIN ACTIVITY DURING SELF-INDUCED ANGER AND ANXIETY
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,DIRP,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
   NIH,CTR CLIN,DEPT PET,BETHESDA,MD 20892.
NR 0
TC 3
Z9 3
U1 1
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 MAY 1
PY 1995
VL 37
IS 9
BP 617
EP 618
DI 10.1016/0006-3223(95)94504-P
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700095
ER

PT J
AU BEAULIEU, S
   ROCHFORD, J
   ROUSSE, I
   GLOWA, J
   BARDEN, N
AF BEAULIEU, S
   ROCHFORD, J
   ROUSSE, I
   GLOWA, J
   BARDEN, N
TI ANTIDEPRESSANT AND GLUCOCORTICOID RECEPTOR MODULATION OF STARTLE AND
   ANXIETY RESPONSES
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
   NIDDK,BETHESDA,MD 20892.
   MCGILL UNIV,MONTREAL,PQ,CANADA.
   UNIV LAVAL,QUEBEC CITY,PQ,CANADA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 622
EP 622
DI 10.1016/0006-3223(95)94518-2
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700109
ER

PT J
AU ALAGHBANDRAD, J
   MCKENNA, K
   GORDON, CT
AF ALAGHBANDRAD, J
   MCKENNA, K
   GORDON, CT
TI CHILDHOOD-ONSET SCHIZOPHRENIA - THE SEVERITY OF PREMORBID COURSE
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 625
EP 625
DI 10.1016/0006-3223(95)94527-4
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700118
ER

PT J
AU JACOBSEN, LK
   HONG, W
   HOMMER, DW
   CASTELLANOS, FX
   FRAZIER, JA
   GIEDD, JN
   GORDON, CT
   KARP, BI
   MCKENNA, K
   RAPOPORT, JL
AF JACOBSEN, LK
   HONG, W
   HOMMER, DW
   CASTELLANOS, FX
   FRAZIER, JA
   GIEDD, JN
   GORDON, CT
   KARP, BI
   MCKENNA, K
   RAPOPORT, JL
TI SMOOTH-PURSUIT EYE-MOVEMENTS IN CHILDHOOD-ONSET SCHIZOPHRENIA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892.
   NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892.
   NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD.
   NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892.
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 625
EP 625
DI 10.1016/0006-3223(95)94528-5
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700119
ER

PT J
AU ELKASHEF, A
   DOUDET, D
   COHEN, R
   WYATT, R
AF ELKASHEF, A
   DOUDET, D
   COHEN, R
   WYATT, R
TI 18F-DOPA PET STUDY OF THE PRESYNAPTIC DOPAMINE FUNCTION IN SCHIZOPHRENIA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,ST ELIZABETHS HOSP,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032.
   UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA.
   NIMH,CEREBRAL METAB LAB,ROCKVILLE,MD.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 626
EP 626
DI 10.1016/0006-3223(95)94532-2
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700123
ER

PT J
AU CASTELLANOS, FX
   ELIA, J
   KRUESI, MJP
   MARSH, WL
   POTTER, WZ
   RITCHIE, GF
   GULOTTA, CS
   RAPOPORT, JL
AF CASTELLANOS, FX
   ELIA, J
   KRUESI, MJP
   MARSH, WL
   POTTER, WZ
   RITCHIE, GF
   GULOTTA, CS
   RAPOPORT, JL
TI CSF HOMOVANILLIC-ACID PREDICTS BEHAVIORAL-RESPONSE TO STIMULANTS IN 47
   ADHD BOYS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892.
   MED COLL PENN,PHILADELPHIA,PA 19129.
   UNIV ILLINOIS,CHICAGO,IL.
   NIMH,CLIN PHARMACOL SECT,BETHESDA,MD 20892.
   VIRGINIA POLYTECH INST & STATE UNIV,BLACKSBURG,VA 24061.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 644
EP 644
DI 10.1016/0006-3223(95)94595-N
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700186
ER

PT J
AU ANDREASON, P
   UMHAU, J
   WILLIAMS, W
   MOMENAN, R
   KERICH, M
   RIO, D
   BROWN, GL
   HOMMER, D
   LINNOILA, M
AF ANDREASON, P
   UMHAU, J
   WILLIAMS, W
   MOMENAN, R
   KERICH, M
   RIO, D
   BROWN, GL
   HOMMER, D
   LINNOILA, M
TI CINGULATE AND RIGHT TEMPORAL GLUCOSE METABOLIC RATES CORRELATE WITH
   IMPULSIVE AGGRESSION IN CLOSED-HEAD INJURY PATIENTS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 645
EP 645
DI 10.1016/0006-3223(95)94599-R
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700190
ER

PT J
AU CANTILLON, M
   JOHNSON, D
   WEINGARTNER, H
   SLATER, S
   BAHRO, M
   LITTLE, J
   SUNDERLAND, T
AF CANTILLON, M
   JOHNSON, D
   WEINGARTNER, H
   SLATER, S
   BAHRO, M
   LITTLE, J
   SUNDERLAND, T
TI THEOPHYLLINE EFFECTS ON OLDER NORMAL VOLUNTEERS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,LCS,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 647
EP 647
DI 10.1016/0006-3223(95)94608-Y
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700199
ER

PT J
AU HITRI, A
   WYATT, RJ
AF HITRI, A
   WYATT, RJ
TI DOPAMINE TRANSPORTER CHANGES IN SCHIZOPHRENIA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 DVA MED CTR,WASHINGTON,DC 20422.
   GEORGETOWN UNIV,SCH MED,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20422.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 653
EP 653
DI 10.1016/0006-3223(95)94626-8
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700217
ER

PT J
AU MATHE, AA
   GEORGE, MS
   FRYE, MA
   POST, RM
AF MATHE, AA
   GEORGE, MS
   FRYE, MA
   POST, RM
TI ELEVATED CONCENTRATIONS OF CSF CGRP MIGHT BE A TRAIT MARKER FOR
   AFFECTIVE-ILLNESS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 KAROLINSKA INST,DEPT CLIN NEUROSCI,STOCKHOLM,SWEDEN.
   NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 654
EP 654
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700222
ER

PT J
AU BAUMANN, MH
   CHAR, GU
   GOODMAN, C
   AYESTAS, M
   ROTHMAN, RB
AF BAUMANN, MH
   CHAR, GU
   GOODMAN, C
   AYESTAS, M
   ROTHMAN, RB
TI EVIDENCE THAT GBR-12909 ATTENUATES DOPAMINERGIC ACTIONS OF COCAINE BY
   BINDING TO DOPAMINE TRANSPORTER SITES IN RAT-BRAIN
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIDA,IRP,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 656
EP 656
DI 10.1016/0006-3223(95)94637-C
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700228
ER

PT J
AU GIEDD, JN
   CASTELLANOS, FX
   RAJAPAKSE, JC
   KAYSEN, D
   VAITUZIS, AC
   VAUSS, YC
   HAMBURGER, SD
   RAPOPORT, JL
AF GIEDD, JN
   CASTELLANOS, FX
   RAJAPAKSE, JC
   KAYSEN, D
   VAITUZIS, AC
   VAUSS, YC
   HAMBURGER, SD
   RAPOPORT, JL
TI CEREBRAL MRI OF HUMAN BRAIN-DEVELOPMENT - AGES 4-18
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892.
RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd,
   Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460;
   Giedd, Jay/0000-0003-2002-8978
NR 0
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE PUBL CO INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 657
EP 657
DI 10.1016/0006-3223(95)94641-9
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700232
ER

PT J
AU HIGLEY, JD
   MEHLMAN, PT
   TAUB, DM
   LINDELL, SG
   SUOMI, SJ
   LINNOILA, M
AF HIGLEY, JD
   MEHLMAN, PT
   TAUB, DM
   LINDELL, SG
   SUOMI, SJ
   LINNOILA, M
TI EXCESSIVE MORTALITY IN FREE-RANGING MALE PRIMATES WITH LOW CSF 5-HIAA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892.
   NICHHD,BETHESDA,MD 20892.
   LABS,YEMASSEE,SC 29945.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 659
EP 659
DI 10.1016/0006-3223(95)94647-F
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700238
ER

PT J
AU SU, T
   TUSKAN, J
   TSAO, L
   PICKAR, D
AF SU, T
   TUSKAN, J
   TSAO, L
   PICKAR, D
TI AGGRESSION IN THE TREATMENT OF INPATIENTS WITH SCHIZOPHRENIA, USING THE
   OVERT AGGRESSION SCALE
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892.
NR 0
TC 0
Z9 0
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 MAY 1
PY 1995
VL 37
IS 9
BP 668
EP 668
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700271
ER

PT J
AU BACHUS, SE
   HYDE, TM
   HERMAN, MM
   KLEINMAN, JE
AF BACHUS, SE
   HYDE, TM
   HERMAN, MM
   KLEINMAN, JE
TI LIMBIC CORTICAL SEROTONIN 1A RECEPTOR MESSENGER-RNA IN SCHIZOPHRENIA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
C1 ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiat.
PD MAY 1
PY 1995
VL 37
IS 9
BP 682
EP 683
DI 10.1016/0006-3223(95)94732-C
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA QX037
UT WOS:A1995QX03700323
ER

PT J
AU FROLOV, VA
   BYCHENKO, AB
   DUNINABARKOVSKYA, AY
   CHIZMADZHEV, YA
   ZIMMERBERG, J
AF FROLOV, VA
   BYCHENKO, AB
   DUNINABARKOVSKYA, AY
   CHIZMADZHEV, YA
   ZIMMERBERG, J
TI FUSION PARTNERS FOR NIH 3T3 HAB2 FIBROBLASTS EXPRESSING HEMAGGLUTININ
SO BIOLOGICHESKIE MEMBRANY
LA Russian
DT Article
ID CELL-FUSION; INFLUENZA-VIRUS; GANGLIOSIDES; PROTEIN; EVENTS
AB In an attempt to work out an experimental system for studying the mechanisms of fusion induced by influenza-virus fusion protein hemagglutinin (HA), several cell lines (PLC/PRF/5, BHK-21, MDCK, VERO) were tested for their ability to fuse with NIH 3T3 HA2b cells that constitutively express HA. Using fluorescent microscopy to follow the dye spread from the labelled cells to the unlabelled ones under conditions that were to activate HA (proteolytic cleavage of inactive MA) and to trigger fusion (pH drop), we have shown that only PLC PRF and BHK-21 cells fused with HA2b cells at a rate comparable with that obtained for RBC. New fusion systems, BHK/HA2b and PLC/HA2b, provide important advantages for further investigations of fusion mechanisms at a single-cell level, as both partners are easily and equally accessible for the manipulations required for high-resolution whole-cell patch-clamp measurements. PLC/HA2b system seems to be more promissing because of clear morphological differences between the partners. The mechanism of fusion tolerance displayed by other cells remians to be explained.
C1 RUSSIAN ACAD MED SCI,DI IVANOVSKII VIROL INST,MOSCOW,RUSSIA.
   MOSCOW MV LOMONOSOV STATE UNIV,AN BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW,RUSSIA.
   NIH,BETHESDA,MD 20892.
RP FROLOV, VA (reprint author), RUSSIAN ACAD SCI,AN FRUMKIN ELECTROCHEM INST,MOSCOW,RUSSIA.
RI Chizmadzhev, Yuri/L-1984-2013
NR 13
TC 1
Z9 2
U1 0
U2 0
PU MEZHDUNARODNAYA KNIGA
PI MOSCOW
PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA
SN 0233-4755
J9 BIOL MEMBRANY
JI Biol. Membr.
PD MAY-JUN
PY 1995
VL 12
IS 3
BP 288
EP 293
PG 6
WC Cell Biology
SC Cell Biology
GA RJ182
UT WOS:A1995RJ18200007
ER

PT J
AU MALINCHIK, S
   YU, LC
AF MALINCHIK, S
   YU, LC
TI ANALYSIS OF EQUATORIAL X-RAY-DIFFRACTION PATTERNS FROM MUSCLE-FIBERS -
   FACTORS THAT AFFECT THE INTENSITIES
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID FROG SKELETAL-MUSCLE; MYOSIN HEADS; ACTIVATION; LATTICE
AB Previously we have shown that cross-bridge attachment to actin and the radial position of the myosin heads surrounding the thick filament backbone affect the equatorial x-ray diffraction intensities in different ways (Yu, 1989). In the present study, other factors frequently encountered experimentally are analyzed by a simple model of the filament lattice. It is shown that the ordering/disordering of filaments, lattice spacing changes, the azimuthal redistributions of cross-bridges, and variations in the ordered/disordered population of cross-bridges surrounding the thick filaments can distinctly affect the equatorial intensities. Consideration of Fourier transforms of individual components of the unit cell can provide qualitative explanations for the equatorial intensity changes. Criteria are suggested that can be used to distinguish the influence of some factors from others.
RP MALINCHIK, S (reprint author), NIAMS,PHYS BIOL LAB,BLDG 6,RM 425,BETHESDA,MD 20892, USA.
NR 29
TC 21
Z9 21
U1 0
U2 0
PU BIOPHYSICAL SOCIETY
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD MAY
PY 1995
VL 68
IS 5
BP 2023
EP 2031
PG 9
WC Biophysics
SC Biophysics
GA RH658
UT WOS:A1995RH65800041
PM 7612844
ER

PT J
AU REYNOLDS, LJ
   KEMPNER, ES
   HUGHES, LL
   DENNIS, EA
AF REYNOLDS, LJ
   KEMPNER, ES
   HUGHES, LL
   DENNIS, EA
TI INACTIVATION OF SECRETORY PHOSPHOLIPASE A(2) BY IONIZING-RADIATION
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID NAJA-NAJA-NAJA; COBRA VENOM PHOSPHOLIPASE-A2; SARCOPLASMIC-RETICULUM;
   MOLECULAR-WEIGHT; SKELETAL-MUSCLE; OLIGOMERIC STRUCTURE;
   SELF-ASSOCIATION; ENERGY-TRANSFER; PUMP PROTEIN; TARGET SIZE
AB The extracellular phospholipase A(2)s (PLA(2)) from cobra venom, rattlesnake venom, and porcine pancreas were analyzed by radiation inactivation to determine their functional aggregation states. The analysis was performed in the presence of the protein transferrin at two different concentrations of PLA(2): 5 mu g/ml and 2500 mu g/ml. The small size of these proteins necessitated the use of high radiation dosages. The catalytic activity of all samples decreased as a single exponential as a function of radiation dosage, to >97% inactivation. Target size analysis of these curves yielded sizes corresponding to dimers for all three PLA(2)s, indicating that all three enzymes exist as dimers or larger aggregates under the conditions studied. An analysis of the amount of intact protein remaining by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that the loss of protein also followed a dimeric size for all three PLA(2)s. The loss of protein as a dimer indicates that transfer of radiation energy is occurring between polypeptides.
C1 UNIV CALIF SAN DIEGO, DEPT CHEM, LA JOLLA, CA 92093 USA.
   NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA.
OI Dennis, Edward A/0000-0003-3738-3140
FU NIGMS NIH HHS [GM-20501]
NR 53
TC 8
Z9 8
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAY
PY 1995
VL 68
IS 5
BP 2108
EP 2114
PG 7
WC Biophysics
SC Biophysics
GA RH658
UT WOS:A1995RH65800051
PM 7612854
ER

PT J
AU CALVERT, RJ
   WEGHORST, CM
   BUZARD, GS
AF CALVERT, RJ
   WEGHORST, CM
   BUZARD, GS
TI PCR AMPLIFICATION OF SILVER-STAINED SSCP BANDS FROM COLD SSCP GELS
SO BIOTECHNIQUES
LA English
DT Note
ID CONFORMATION POLYMORPHISM ANALYSIS; NONISOTOPIC SSCP; MUTATIONS; DNA;
   GENE
C1 NCI,FREDERICK,MD 21701.
   NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702.
RP CALVERT, RJ (reprint author), US FDA,MODI LAB,HFS-452,8301 MUIRKIRK RD,LAUREL,MD 20708, USA.
NR 14
TC 10
Z9 11
U1 0
U2 0
PU EATON PUBLISHING CO
PI NATICK
PA 154 E. CENTRAL ST, NATICK, MA 01760
SN 0736-6205
J9 BIOTECHNIQUES
JI Biotechniques
PD MAY
PY 1995
VL 18
IS 5
BP 782
EP &
PG 0
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QX422
UT WOS:A1995QX42200014
PM 7619478
ER

PT J
AU LIU, PP
   HAJRA, A
   WIJMENGA, C
   COLLINS, FS
AF LIU, PP
   HAJRA, A
   WIJMENGA, C
   COLLINS, FS
TI MOLECULAR PATHOGENESIS OF THE CHROMOSOME-16 INVERSION IN THE M4EO
   SUBTYPE OF ACUTE MYELOID-LEUKEMIA
SO BLOOD
LA English
DT Review
ID ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA;
   BONE-MARROW EOSINOPHILIA; MYOSIN HEAVY-CHAIN; METALLOTHIONEIN
   GENE-CLUSTER; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA;
   REPETITIVE DNA-SEQUENCES; HERITABLE FRAGILE SITES; CELL RECEPTOR-GAMMA
RP LIU, PP (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BLDG 49,ROOM 3A18,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
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 111
TC 176
Z9 179
U1 0
U2 2
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0006-4971
J9 BLOOD
JI Blood
PD MAY 1
PY 1995
VL 85
IS 9
BP 2289
EP 2302
PG 14
WC Hematology
SC Hematology
GA QW602
UT WOS:A1995QW60200001
PM 7727763
ER

PT J
AU RAGNI, MV
   LOFARO, ML
   DEGRUTTOLA, V
   VANDERHORST, C
   EYSTER, ME
   KESSLER, CM
   GJERSET, GF
   HO, M
   PARENTI, DM
   DAFNI, U
   RASHEED, S
   KORVICK, JA
   MERIGAN, TC
   FISCUS, S
   GUPTA, P
   KATZMAN, M
   SHAFER, R
   MEYER, WS
   COOMBS, RW
   LANDRY, BS
   KASDAN, P
   NERHOOD, L
   STOWELL, R
   KAZIAL, K
   BROWNSTEIN, A
   KRAMER, AS
   WASSERMAN, S
   BLOODGOOD, K
   MCMAHON, D
   SUPERDOCK, B
   ISRAELSKI, DM
   CAIN, P
   CARFAGNA, E
   QUINLAN, C
   HAWLEY, P
   LELACHEUR, SF
   MUENCH, L
   COLLIER, AC
   CHENG, L
   LI, XY
   MORSE, G
AF RAGNI, MV
   LOFARO, ML
   DEGRUTTOLA, V
   VANDERHORST, C
   EYSTER, ME
   KESSLER, CM
   GJERSET, GF
   HO, M
   PARENTI, DM
   DAFNI, U
   RASHEED, S
   KORVICK, JA
   MERIGAN, TC
   FISCUS, S
   GUPTA, P
   KATZMAN, M
   SHAFER, R
   MEYER, WS
   COOMBS, RW
   LANDRY, BS
   KASDAN, P
   NERHOOD, L
   STOWELL, R
   KAZIAL, K
   BROWNSTEIN, A
   KRAMER, AS
   WASSERMAN, S
   BLOODGOOD, K
   MCMAHON, D
   SUPERDOCK, B
   ISRAELSKI, DM
   CAIN, P
   CARFAGNA, E
   QUINLAN, C
   HAWLEY, P
   LELACHEUR, SF
   MUENCH, L
   COLLIER, AC
   CHENG, L
   LI, XY
   MORSE, G
TI RANDOMIZED STUDY OF DIDANOSINE MONOTHERAPY AND COMBINATION THERAPY WITH
   ZIDOVUDINE IN HEMOPHILIC AND NONHEMOPHILIC SUBJECTS WITH ASYMPTOMATIC
   HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION
SO BLOOD
LA English
DT Article
ID AIDS-RELATED COMPLEX; HIV-1 REVERSE-TRANSCRIPTASE; FACTOR-VIII; PHASE-I;
   INTERMITTENT REGIMENS; BLOOD-TRANSFUSIONS; CUBIC MILLIMETER; CONTROLLED
   TRIAL; AZT; 2',3'-DIDEOXYINOSINE
AB To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm(3) stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddl 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm(3) and 42/mm(3), than arms B and C, 105/mm(3) and 114/mm(3), respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients. (C) 1995 by The American Society of Hematology.
C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115.
   UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC.
   PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033.
   GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC.
   UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103.
   NIAID,AIDS PROGRAM,BETHESDA,MD 20892.
   STANFORD UNIV,SCH MED,CTR AIDS RES,STANFORD,CA 94305.
RP RAGNI, MV (reprint author), UNIV PITTSBURGH,SCH MED,HEMOPHILIA CTR WESTERN PENN,DEPT MED,812 5TH AVE,PITTSBURGH,PA 15219, USA.
FU NIAID NIH HHS [AI-82678, AI 25868, AI-95030]
NR 41
TC 21
Z9 21
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0006-4971
J9 BLOOD
JI Blood
PD MAY 1
PY 1995
VL 85
IS 9
BP 2337
EP 2346
PG 10
WC Hematology
SC Hematology
GA QW602
UT WOS:A1995QW60200007
PM 7727768
ER

PT J
AU BECKWITH, M
   RUSCETTI, FW
   SING, GK
   URBA, WJ
   LONGO, DL
AF BECKWITH, M
   RUSCETTI, FW
   SING, GK
   URBA, WJ
   LONGO, DL
TI ANTI-IGM INDUCES TRANSFORMING GROWTH-FACTOR-BETA SENSITIVITY IN A HUMAN
   B-LYMPHOMA CELL-LINE - INHIBITION OF GROWTH IS ASSOCIATED WITH A
   DOWN-REGULATION OF MUTANT P53
SO BLOOD
LA English
DT Article
ID WILD-TYPE P53; GASTRIC-CARCINOMA CELLS; MYELOID LEUKEMIC-CELLS;
   TGF-BETA; RETINOBLASTOMA PROTEIN; EPITHELIAL-CELLS; LYMPHOCYTES-B; G1
   PHASE; APOPTOSIS; DEATH
AB We wished to examine the role of transforming growth factor-beta (TGF-beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-lg antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G(1) of the cell cycle, we examined the ability of TGF-beta to modulate two tumor suppressor proteins known to be critical regulators of the G(1)/S transition, Rb and p53, Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti-Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53, We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled. (C) 1995 by The American Society of Hematology.
C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702.
   ROYAL BRISBANE HOSP FDN,CLIN RES CTR,BRISBANE,QLD,AUSTRALIA.
   PROVIDENCE MED CTR,EARLE A CHILES RES INST,PORTLAND,OR.
RP BECKWITH, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702, USA.
NR 52
TC 22
Z9 23
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 0006-4971
J9 BLOOD
JI Blood
PD MAY 1
PY 1995
VL 85
IS 9
BP 2461
EP 2470
PG 10
WC Hematology
SC Hematology
GA QW602
UT WOS:A1995QW60200021
PM 7727777
ER

PT J
AU SCHREIBER, JL
   BREIER, A
   PICKAR, D
AF SCHREIBER, JL
   BREIER, A
   PICKAR, D
TI EXPRESSED EMOTION - TRAIT OR STATE
SO BRITISH JOURNAL OF PSYCHIATRY
LA English
DT Article
ID FAMILY
AB Background, This exploratory study addresses the question of whether expressed emotion (EE) is a response characteristic of the parent (trait) or a parental response to specific circumstances or persons (state).
   Method. Seventeen parents participated in two audiotaped interviews, using modified versions of the Camberwell Family Interview. One interview concerned the child with chronic schizophrenia and the other a well sibling. Subsequent ratings of the EE variables of critical comments (CC), emotional overinvolvement (EOI) and warmth were completed and compared.
   Results. EE response patterns directed towards patients, as compared with towards siblings, were significantly different on two measures: EOI (P=0.01) and warmth (P=0.02). The parents showed significantly more emotional overinvolvement with the child with schizophrenia and significantly more warmth towards the well child.
   Conclusions. These data suggest that the EE variables of EOI and warmth are related to the state of child, and the lack of a significant difference in CC suggests that this is a parental trait.
RP SCHREIBER, JL (reprint author), NIMH,LCSW,10-4N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 9
TC 31
Z9 31
U1 1
U2 1
PU ROYAL COLLEGE OF PSYCHIATRISTS
PI LONDON
PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X
   8PG
SN 0007-1250
J9 BRIT J PSYCHIAT
JI Br. J. Psychiatry
PD MAY
PY 1995
VL 166
BP 647
EP 649
DI 10.1192/bjp.166.5.647
PG 3
WC Psychiatry
SC Psychiatry
GA QY332
UT WOS:A1995QY33200013
PM 7620751
ER

PT J
AU BERTRAM, R
   BUTTE, MJ
   KIEMEL, T
   SHERMAN, A
AF BERTRAM, R
   BUTTE, MJ
   KIEMEL, T
   SHERMAN, A
TI TOPOLOGICAL AND PHENOMENOLOGICAL CLASSIFICATION OF BURSTING OSCILLATIONS
SO BULLETIN OF MATHEMATICAL BIOLOGY
LA English
DT Article
ID PANCREATIC BETA-CELL; MODEL; NEURON; BIFURCATION; MECHANISMS; EQUATIONS;
   CURRENTS; DYNAMICS
AB We describe a classification scheme for bursting oscillations which encompasses many of those found in the literature on bursting in excitable media. This is an extension of the scheme of Rinzel (in Mathematical Topics in Population Biology, Springer, Berlin, 1987), put in the context of a sequence of horizontal cuts through a two-parameter bifurcation diagram. We use this to describe the phenomenological character of different types of bursting, addressing the issue of how well the bursting can be characterized given the limited amount of information often available in experimental settings.
C1 BROWN UNIV,PROVIDENCE,RI 02912.
   UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742.
RP BERTRAM, R (reprint author), NIDDK,MATH RES BRANCH,BSA BLDG,SUITE 350,BETHESDA,MD 20814, USA.
OI Butte, Manish/0000-0002-4490-5595
FU NIMH NIH HHS [MH-44809]; NINDS NIH HHS [NS-16803]
NR 41
TC 183
Z9 187
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0092-8240
J9 B MATH BIOL
JI Bull. Math. Biol.
PD MAY
PY 1995
VL 57
IS 3
BP 413
EP 439
DI 10.1016/S0092-8240(05)81776-8
PG 27
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology
GA QM415
UT WOS:A1995QM41500003
PM 7728115
ER

PT J
AU THORP, BH
   EKMAN, S
   JAKOWLEW, SB
   GODDARD, C
AF THORP, BH
   EKMAN, S
   JAKOWLEW, SB
   GODDARD, C
TI PORCINE OSTEOCHONDROSIS - DEFICIENCIES IN TRANSFORMING
   GROWTH-FACTOR-BETA AND INSULIN-LIKE GROWTH-FACTOR-I
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE CHONDROCYTE DIFFERENTIATION; CARTILAGE TGF-BETA; IGF-I OSTEOCHONDROSIS;
   PIG
ID EPIPHYSEAL CARTILAGE COMPLEX; MATRIX PROTEINS; IMMUNOHISTOCHEMICAL
   LOCALIZATION; TIBIAL DYSCHONDROPLASIA; PLATE CHONDROCYTES; BONE-CELLS;
   HORMONE; EXPRESSION; EMBRYO; CHICK
AB Osteochondrosis and dyschondroplasia are common multifocal disturbances of endochondral ossification in many species of domestic animals, and are characterized by the retention of avascular cartilage. These cartilage disorders are characterized by a failure of chondrocyte differentiation, matrix mineralisation and its replacement by bone. Rabbit polyclonal antibodies to transforming growth factor-beta (TGF-beta) and to insulin-like growth factor-I (IGF-I) were used to detect the two growth factors in normal and osteochondrotic porcine epiphyses. In the normal pig epiphyses IGF-I and TGF-beta were present in the chondrocytes of the epiphyseal hyaline cartilage and IGF-I was readily localised to the hypertrophic chondrocytes in the growth cartilage adjacent to the epiphyseal ossification centre. Both growth factors were found to be deficient in chondrocytes at sites of osteochondrosis. Both these growth factors are thought to be involved in the cascade of events associated with chondrocyte function during endochondral ossification. Deficiencies in TGF-beta and IGF-I demonstrated in porcine osteochondrosis and previously shown in avian dyschondroplasia suggest further similarities in the pathogenesis of these conditions
C1 SWEDISH UNIV AGR SCI,FAC VET MED,DEPT PATHOL,S-75007 UPPSALA,SWEDEN.
   NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850.
RP THORP, BH (reprint author), ROSLIN INST EDINBURGH,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND.
NR 37
TC 14
Z9 16
U1 1
U2 1
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0171-967X
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD MAY
PY 1995
VL 56
IS 5
BP 376
EP 381
DI 10.1007/BF00301606
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QT993
UT WOS:A1995QT99300009
PM 7621345
ER

PT J
AU JOHNSTONE, PAS
   DEGRAFF, WG
   MITCHELL, JB
AF JOHNSTONE, PAS
   DEGRAFF, WG
   MITCHELL, JB
TI PROTECTION FROM RADIATION-INDUCED CHROMOSOMAL-ABERRATIONS BY THE
   NITROXIDE TEMPOL
SO CANCER
LA English
DT Article
DE RADIOPROTECTION; NITROXIDE; TEMPOL; CHROMOSOMAL ABERRATION; CYTOGENETICS
ID INDUCED CELL DEATH; TOPICAL APPLICATION; INDUCED ALOPECIA; DAMAGE;
   LYMPHOCYTES; SURVIVAL
AB Background. The nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable, free radical that exhibits protection from ionizing radiation damage and from oxidative stress mediated through exposure of cells to superoxide or hydrogen peroxide. Radiation protection has been observed in both in vivo and in vitro models. To understand the mechanism of Tempol-mediated radioprotection better, the production of radiation-induced chromosome aberrations was evaluated. This study analyzed Tempol-mediated radioprotection of human peripheral blood lymphocytes (PBLs).
   Methods. Peripheral blood lymphocytes were exposed to control (OmM), 10 mM (Tp10), and 50 mM (Tp50) concentrations of Tempol for 20 minutes before irradiation with 0, 150, 300, and 450 cGy. One quarter mi whole blood was cultured in F12 medium and phytohemagglutinin at 37 degrees C for 49, 54, 59, and 64 hours. Colcemide was added to each sample for the last 5 hours before harvest. Cells were harvested, treated with hypotonic solution, and fixed before dropping on cold clean slides. Mitotic indices and frequency of dicentric, ring, and triradial chromosomal aberrations were determined at 1000X magnification for each treatment group at each collection point.
   Results. Treatment of cells with Tempol alone did not induce the chromosomal aberration frequency above that for unirradiated controls. Radiation dose response curves for total chromosome aberration production revealed radioprotection for Tempol treatment for both 10 and 50 mM exposures. Tempol protection factors (assessed at 0.2 aberrations/cell level) for Tp 10 and Tp 50 were 2.2 and 2.8, respectively.
   Conclusions. Tempol protects against radiation-induced chromosome aberrations in human PBLs. This finding is consistent with and lends support to previous studies in which Tempol was reported to enhance cell survival and reduce radiation-induced DNA double strand breaks
C1 NCI,DIV CANC TREATMENT,RADIAT BIOL BRANCH,BETHESDA,MD 20892.
   USN,MED CTR,DIV RADIAT ONCOL,SAN DIEGO,CA 92152.
NR 19
TC 23
Z9 24
U1 0
U2 3
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0008-543X
J9 CANCER
JI Cancer
PD MAY 1
PY 1995
VL 75
IS 9
BP 2323
EP 2327
DI 10.1002/1097-0142(19950501)75:9<2323::AID-CNCR2820750922>3.0.CO;2-2
PG 5
WC Oncology
SC Oncology
GA QU339
UT WOS:A1995QU33900021
PM 7712443
ER

PT J
AU BRINTON, LA
   POTISCHMAN, NA
   SWANSON, CA
   SCHOENBERG, JB
   COATES, RJ
   GAMMON, MD
   MALONE, KE
   STANFORD, JL
   DALING, JR
AF BRINTON, LA
   POTISCHMAN, NA
   SWANSON, CA
   SCHOENBERG, JB
   COATES, RJ
   GAMMON, MD
   MALONE, KE
   STANFORD, JL
   DALING, JR
TI BREAST-FEEDING AND BREAST-CANCER RISK
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE BREAST CANCER; BREAST FEEDING; UNITED STATES; WOMEN
ID CHINESE-WOMEN; UNITED-STATES; YOUNG-WOMEN; LACTATION; ASSOCIATION;
   PREGNANCY; POPULATION; AGE; 1ST
AB A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI] = 0.7-1.0), This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR = 0.67, CI = 0.4-1.1 for an average period per child of 72 or more weeks), Women who began to breastfeed at a young age (< 22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited Use of medications to stop breast milk was unrelated to risk (RR = 1.04), The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks), Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.
C1 NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ.
   EMORY UNIV,ROLLINS SCH PUBL HLTH,ATLANTA,GA.
   COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY.
   UNIV WASHINGTON,FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98195.
RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA.
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
NR 29
TC 52
Z9 55
U1 1
U2 2
PU RAPID SCIENCE PUBLISHERS
PI LONDON
PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 1995
VL 6
IS 3
BP 199
EP 208
DI 10.1007/BF00051791
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA QX940
UT WOS:A1995QX94000002
PM 7612799
ER

PT J
AU ALAVANJA, MCR
   BROWNSON, RC
   BENICHOU, J
   SWANSON, C
   BOICE, JD
AF ALAVANJA, MCR
   BROWNSON, RC
   BENICHOU, J
   SWANSON, C
   BOICE, JD
TI ATTRIBUTABLE RISK OF LUNG-CANCER IN LIFETIME NONSMOKERS AND LONG-TERM
   EX-SMOKERS (MISSOURI, UNITED-STATES)
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE FEMALES; LUNG CANCER; RADON; SATURATED FAT; TOBACCO SMOKING; UNITED
   STATES
ID WOMEN; SMOKING
AB A population-based, case-control study of incident lung cancer among women in Missouri (United States) who were lifetime nonsmokers and long-term ex-smokers was conducted between 1986 and 1992. The study included 618 lung cancer cases and 1,402 population-based, age matched controls. Information on lung-cancer risk factors was obtained by interviewing cases, next-of-kin of cases (36 percent and 64 percent of the cases, respectively) and controls. Year-long radon measurements also were sought in every dwelling occupied for the previous five to 30 years. Population attributable risks (PAR) for specific risk factors were computed for all subjects, for lifetime nonsmokers, for long-term ex-smokers, by histologic cell type (i.e., adenocarcinoma cf nonadenocarcinoma) and for direct interviews with case (for living cases) and for next-of-kin interviews (for dead cases or cases too ill to complete an interview). The mean age at lung cancer diagnosis was 71 years, and nearly 50 percent of the lung cancers were histologically confirmed adenocarcinomas. Almost 40 percent of all lung cancers among lifetime nonsmokers and almost 50 percent of lung cancers among all subjects could be explained by the risk factors under study. Dietary intake of saturated fat and nonmalignant lung disease were the two leading identified risk factors for lung cancer among the lifetime nonsmokers, followed by environmental tobacco smoke, and occupational exposures to known carcinogens. A small nonsignificant risk was found for study subjects exposed to median domestic radon concentration of 4 pCi/l (25-year time-weight average). Since only a small fraction of the population is exposed at this level, it is estimated that the PAR for domestic radon was less than two percent in Missouri. The risk for saturated fat intake was similar for lifetime nonsmokers, ex-smokers, adenocarcinoma cases, and nonadenocarcinoma cases; however, the increased risk was much more pronounced for next-of-kin interviews (PAR = 31 percent) than for interviews with the study subjects (PAR = nine percent). A similar pattern of PAR was identified among ex-smokers but, in this group, the lingering effect of a history of smoking was also very important. Along with saturated fat intake (PAR = 20 percent), the combined effect of previous active and passive smoking even after 15 years of cessation of active smoking was responsible for more lung cancer than any other risk factor under study (PAR = 59 percent).
C1 ST LOUIS UNIV,SCH PUBL HLTH,DEPT COMMUNITY HLTH,ST LOUIS,MO.
RP ALAVANJA, MCR (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN-543,6130 EXECUT BLVD,BETHESDA,MD 20892, USA.
NR 29
TC 21
Z9 21
U1 2
U2 3
PU RAPID SCIENCE PUBLISHERS
PI LONDON
PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 1995
VL 6
IS 3
BP 209
EP 216
DI 10.1007/BF00051792
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA QX940
UT WOS:A1995QX94000003
PM 7612800
ER

PT J
AU BRAUN, MM
   HELZLSOUER, KJ
   HOLLIS, BW
   COMSTOCK, GW
AF BRAUN, MM
   HELZLSOUER, KJ
   HOLLIS, BW
   COMSTOCK, GW
TI PROSTATE-CANCER AND PREDIAGNOSTIC LEVELS OF SERUM VITAMIN-D METABOLITES
   (MARYLAND, UNITED-STATES)
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE CANCER; PROSTATE; VITAMIN D; UNITED STATES
AB An hypothesis has been forwarded linking prostate cancer to low serum levels of vitamin D metabolites. We sought to test this hypothesis using sera obtained in a large, prospective cohort study. A serum bank in Washington County, Maryland (United States) has stored sera obtained from 20,305 county residents during a blood collection campaign undertaken in August through November 1974, We studied sera obtained from 61 residents who were diagnosed with prostate cancer during the period 1980 through 1992. Each prostate cancer case was matched to two controls on age (+/-1yr) and race. Controls had donated blood in the same blood-collection campaign and had not been diagnosed with prostate cancer through 1992. Serum levels of vitamin D metabolites did not differ significantly between cases and controls. Mean 25-hydroxyvitamin D (25-D) levels were 34.3 ng/ml and 33.2 ng/ml, and mean 1,25-dihydroxyvitamin D (1,25-D) levels were 41.0 pg/ml and 40.1 pg/ml, in cases and controls, respectively. No statistically significant trends or differences between cases and controls were found in an analysis by quintile of serum level. We also did not observe the association of vitamin D metabolites with prostate cancer to be strongest among older men with more severe disease, as previously has been reported In summary, although our study's power was limited, our findings provide little support for the hypothesis that vitamin D metabolite levels are associated strongly with subsequent risk for prostate cancer.
C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD.
RP BRAUN, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 443,BETHESDA,MD 20892, USA.
NR 15
TC 138
Z9 138
U1 0
U2 4
PU RAPID SCIENCE PUBLISHERS
PI LONDON
PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 1995
VL 6
IS 3
BP 235
EP 239
DI 10.1007/BF00051795
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA QX940
UT WOS:A1995QX94000006
PM 7612803
ER

PT J
AU SHRAYER, D
   BOGAARS, H
   HEARING, VJ
   MAIZEL, A
   WANEBO, H
AF SHRAYER, D
   BOGAARS, H
   HEARING, VJ
   MAIZEL, A
   WANEBO, H
TI FURTHER CHARACTERIZATION OF A CLINICALLY RELEVANT MODEL OF MELANOMA
   METASTASIS AND AN EFFECTIVE VACCINE
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE MELANOMA; POLYVALENT ANTIGEN; MONOCLONAL ANTIBODY; POLYCLONAL ANTIBODY;
   INTERLEUKIN-2; IMMUNIZATION
ID FORMALINIZED EXTRACELLULAR ANTIGENS; TUMOR-INFILTRATING LYMPHOCYTES;
   MURINE MELANOMA; NUDE-MICE; PULMONARY METASTASES; CELL-LINE; T-CELLS;
   B16; EXPRESSION; GROWTH
AB A major problem in evaluating the effectiveness of tumor cell vaccination and other biological therapies is the variability of experimental models. In this study we have further developed and characterized a model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination: stage I - growth of the primary (local) tumor, stage II - dissemination to regional lymph nodes, and stage III - metastasis to distant organs (lungs). C57BL/6 mice were challenged subcutaneously with B16 F10 murine melanoma cells in the midtail, and within 3 weeks 100% of the mice had local tumors growing in their tails. By 5-7 weeks after challenge, most of the mice had developed metastases to the inguinal lymph nodes and subsequently had metastatic colonies in the lungs and in the bone marrow. Preimmunization of mice with a formalinized extracellular antigen vaccine, derived from B16 F10 melanoma cells, provided partial inhibition of the growth of the primary melanoma tumors, as well as reducing the number of metastases to the regional (inguinal) lymph nodes and lungs along with concomitantly increasing survival time. This model for melanoma metastasis provides a reasonable and reproducible test system for the study of anti-melanoma immunity and the different cellular and humoral mechanisms involved.
C1 BROWN UNIV,ROGER WILLIAMS CANC CTR,DEPT SURG,PROVIDENCE,RI 02908.
   NCI,CELL BIOL LAB,BETHESDA,MD 20892.
RP SHRAYER, D (reprint author), BROWN UNIV,ROGER WILLIAMS CANC CTR,DEPT PATHOL,825 CHALKSTONE AVE,PROVIDENCE,RI 02908, USA.
FU NCI NIH HHS [R37 CA45148, R30 CA13943]
NR 39
TC 12
Z9 12
U1 0
U2 1
PU SPRINGER VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAY
PY 1995
VL 40
IS 5
BP 277
EP 282
DI 10.1007/BF01519626
PG 6
WC Oncology; Immunology
SC Oncology; Immunology
GA RF806
UT WOS:A1995RF80600001
PM 7600558
ER

PT J
AU ALMOUSTAFA, AE
   TSAO, MS
   BATTEY, JF
   VIALLET, J
AF ALMOUSTAFA, AE
   TSAO, MS
   BATTEY, JF
   VIALLET, J
TI EXPRESSION OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR CONFERS A
   GROWTH-RESPONSE TO BOMBESIN IN IMMORTALIZED HUMAN BRONCHIAL
   EPITHELIAL-CELLS
SO CANCER RESEARCH
LA English
DT Note
ID LUNG-CARCINOMA CELLS
AB We have introduced a human gastrin-releasing peptide receptor expression vector into an immortalized human bronchial epithelial cell normally unresponsive to the ligand bombesin, Successfully transfected cells express specific binding sites at a density similar to that found at the surface of human lung cancer cells and show an elevation of intracellular calcium concentration in response to bombesin, We found that cellular strains expressing the receptor showed a growth stimulation in response to bombesin in proportion to cell surface receptor density, We conclude that expression of bombesin receptors contributes to the growth potential of human bronchial epithelial cells.
C1 MONTREAL GEN HOSP,RES INST,DEPT ONCOL,MONTREAL,PQ H3G 1A4,CANADA.
   MONTREAL GEN HOSP,RES INST,DEPT MED,MONTREAL,PQ H3G 1A4,CANADA.
   MONTREAL GEN HOSP,RES INST,DEPT PATHOL,MONTREAL,PQ H3G 1A4,CANADA.
   MCGILL UNIV,MONTREAL,PQ H3G 1A4,CANADA.
   NIH,BIOL CHEM LAB,BETHESDA,MD 20892.
NR 17
TC 5
Z9 5
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 MAY 1
PY 1995
VL 55
IS 9
BP 1853
EP 1855
PG 3
WC Oncology
SC Oncology
GA QV015
UT WOS:A1995QV01500012
PM 7728752
ER

PT J
AU KOHN, EC
   LIOTTA, LA
AF KOHN, EC
   LIOTTA, LA
TI MOLECULAR INSIGHTS INTO CANCER INVASION - STRATEGIES FOR PREVENTION AND
   INTERVENTION
SO CANCER RESEARCH
LA English
DT Article
ID TUMOR-CELL INVASION; HUMAN AMNIOTIC MEMBRANE; IV COLLAGENASE; TISSUE
   INHIBITOR; GENE-EXPRESSION; TYROSINE PHOSPHORYLATION; INOSITOL
   PHOSPHATES; CARCINOMA-CELLS; BREAST-CANCER; METASTASIS
AB The diagnosis and treatment of solid tumors usually begins at a late stage when most patients already have occult or overt metastasis. Many years of cancer progression precede diagnosis of most solid tumors. Novel noncytotoxic therapeutics may be specially suited for administration during this interval. An important window of intervention can be defined as the period during which transition from a hyperproliferative state to acquisition of the capacity for invasion and metastasis occurs. Investigation of the molecular basis of invasion is uncovering strategies for delaying progression of preinvasive carcinoma and treatment of primary tumors and established metastasis, Although tumor cell invasion might not be rate limiting for the growth of metastasis, anti-invasive agents can block tumor angiogenesis and thereby indirectly block metastasis growth. Two classes of molecular anti-invasion targets exist: (a) cell surface and extracellular proteins, which mediate sensing, adhesion, and proteolysis; and (b) signal transduction pathways, which regulate invasion, angiogenesis, and proliferation. Both categories of targets yield treatment approaches that are now being tested in the clinic. Metalloproteinase inhibitors, such as BB94, are based on the recognition that metalloproteinases play a necessary role in invasion and angiogenesis, The orally active signal transduction inhibitor carboxyamidotriazole modulates non-voltage-gated calcium influx-regulated signal pathways and reversibly inhibits tumor invasion, growth, and angiogenesis. Blockade of invasion, angiogenesis, or cellular signal pathways is likely to generate a cytostatic, rather than a cytotoxic effect. Cytostatic therapy constitutes an alternative paradigm for clinical translation that may complement conventional cytotoxic therapy. For patients with newly diagnosed solid tumors, long-term cytostatic therapy could potentially create a state of metastasis dormancy or delay the time to overt relapse following cytotoxic agent-induced remission, Clinical toxicity and pharmacology using oral cytostatic agents in phase I trials and in adjuvant settings will provide an important foundation for the translation of this approach to the preinvasive carcinoma period.
RP KOHN, EC (reprint author), NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892, USA.
NR 92
TC 441
Z9 468
U1 1
U2 8
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 MAY 1
PY 1995
VL 55
IS 9
BP 1856
EP 1862
PG 7
WC Oncology
SC Oncology
GA QV015
UT WOS:A1995QV01500013
PM 7728753
ER

PT J
AU DLUGOSZ, AA
   CHENG, C
   WILLIAMS, EK
   DARWICHE, N
   DEMPSEY, PJ
   MANN, B
   DUNN, AR
   COFFEY, RJ
   YUSPA, SH
AF DLUGOSZ, AA
   CHENG, C
   WILLIAMS, EK
   DARWICHE, N
   DEMPSEY, PJ
   MANN, B
   DUNN, AR
   COFFEY, RJ
   YUSPA, SH
TI AUTOCRINE TRANSFORMING GROWTH-FACTOR-ALPHA IS DISPENSIBLE FOR
   V-RAS(HA)-INDUCED EPIDERMAL NEOPLASIA - POTENTIAL INVOLVEMENT OF
   ALTERNATE EPIDERMAL GROWTH-FACTOR RECEPTOR LIGANDS
SO CANCER RESEARCH
LA English
DT Article
ID CARCINOMA CELL-LINE; TGF-ALPHA; TRANSGENIC MICE; MESSENGER-RNA; MOUSE
   SKIN; PSORIATIC EPIDERMIS; HUMAN KERATINOCYTES; HUMAN COLON; HA-RAS;
   DIFFERENTIATION
AB Autocrine epidermal growth factor receptor activation by transforming growth factor alpha (TGF alpha) has been implicated in growth stimulation during epithelial neoplasia. Using keratinocytes isolated from mice with genetic defects in TGF alpha expression, me tested whether TGF alpha is required for transformation by the v-ras(Ha) oncogene, Introduction of v-ras(Ha) into primary epidermal cultures using a retroviral vector stimulated growth of both control (TGF alpha +/+, BALB/c) and TGF alpha-deficient (TGF alpha -/-, wa-l) keratinocytes, Moreover, v-ras(Ha) elicited characteristic changes in marker expression (keratin 1 was suppressed; keratin 8 was induced), previously shown to be associated with epidermal growth factor (EGF) receptor activation, in both TGF alpha +/+ and TGF alpha -/- keratinocytes. v-ras(Ha) markedly increased secreted (>10-fold) and cell-associated (2-3-fold) TGF alpha levels in keratinocytes from TGF alpha +/+ and BALB/c mice, but not TGF alpha -/- or wa-l mice, Based on Northern blot analysis, v-ras(Ha) induced striking up regulation of transcripts encoding the additional EGF family members amphiregulin, heparin-binding EGF-like growth factor, and betacellulin in cultured keratinocytes from all four mouse strains, Interestingly, in addition to the normal 4.5-kilobase TGF alpha transcript, loa-l keratinocytes expressed two additional TGF alpha transcripts, 4.7 and 5.2 kilobases long, All three transcripts were up-regulated in response to v-ras(Ha), as well as exogenous TGF alpha or keratinocyte growth factor treatment, and were also detected in RNA isolated from wa-l brain and skin, In vivo, v-ras(Ha) keratinocytes from control as well as TGF alpha-deficient mice produced squamous tumors when grafted onto nude mice, and these lesions expressed high levels of amphiregulin, heparin-binding EGF-like growth factor, and betacellulin mRNA, regardless of their TGF alpha status. These findings indicate that TGF alpha is not essential for epidermal neoplasia induced by the v-ras(Ha) oncogene and suggest that another EGF family member(s) may contribute to autocrine growth stimulation of ras-transformed keratinocytes.
C1 VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232.
   VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232.
   ROYAL MELBOURNE HOSP,LUDWIG INST CANC RES,PARKVILLE,VIC 3050,AUSTRALIA.
RP DLUGOSZ, AA (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37 RM 3B08,BETHESDA,MD 20892, USA.
OI Darwiche, Nadine/0000-0002-1862-5426
FU NCI NIH HHS [CA46413]
NR 71
TC 57
Z9 57
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAY 1
PY 1995
VL 55
IS 9
BP 1883
EP 1893
PG 11
WC Oncology
SC Oncology
GA QV015
UT WOS:A1995QV01500017
PM 7728756
ER

PT J
AU APLAN, PD
   JOHNSON, BE
   RUSSELL, E
   CHERVINSKY, DS
   KIRSCH, IR
AF APLAN, PD
   JOHNSON, BE
   RUSSELL, E
   CHERVINSKY, DS
   KIRSCH, IR
TI CLONING AND CHARACTERIZATION OF TCTA, A GENE LOCATED AT THE SITE OF A
   T(1-3) TRANSLOCATION
SO CANCER RESEARCH
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL LUNG-CANCER; LOOP-HELIX PROTEIN;
   RETINOBLASTOMA GENE; CHROMOSOMAL REGIONS; SCL GENE; CARCINOMA;
   HETEROZYGOSITY; GROWTH; 3P
AB We have cloned and characterized a novel gene at the site of a t(1;3)(p34;p21) translocation breakpoint in T-cell acute lymphoblastic leukemia. A cDNA for this gene, for which we propose the designation TCTA (T-cell leukemia translocation-associated gene), has been cloned. TCTA mRNA is expressed ubiquitously in normal tissues, with the highest levels of expression seen in the kidney. The TCTA gene is conserved throughout evolution in organisms ranging from Drosophila to humans. A short open reading frame encodes a predicted M(r) 12,000 protein without strong homology to any previously reported proteins. Of note, genomic Southern blots demonstrated a reduced TCTA signal in three of four small cell lung cancer cell lines tested, suggesting loss of one of the two copies of the gene.
C1 ROSWELL PK CANC INST,DEPT MOLEC MED,BUFFALO,NY 14263.
   CHILDRENS HOSP BUFFALO,DIV HEMATOL ONCOL,BUFFALO,NY.
   NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889.
RP APLAN, PD (reprint author), ROSWELL PK CANC INST,DEPT PEDIAT,ELM & CARLTON ST,BUFFALO,NY 14263, USA.
RI Aplan, Peter/K-9064-2016
NR 35
TC 25
Z9 26
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 MAY 1
PY 1995
VL 55
IS 9
BP 1917
EP 1921
PG 5
WC Oncology
SC Oncology
GA QV015
UT WOS:A1995QV01500021
PM 7728759
ER

PT J
AU RONG, S
   DONEHOWER, LA
   HANSEN, MF
   STRONG, L
   TAINSKY, M
   JEFFERS, M
   RESAU, JH
   HUDSON, E
   TSARFATY, I
   VANDEWOUDE, GF
AF RONG, S
   DONEHOWER, LA
   HANSEN, MF
   STRONG, L
   TAINSKY, M
   JEFFERS, M
   RESAU, JH
   HUDSON, E
   TSARFATY, I
   VANDEWOUDE, GF
TI MET PROTOONCOGENE PRODUCT IS OVEREXPRESSED IN TUMORS OF P53-DEFICIENT
   MICE AND TUMORS OF LI-FRAUMENI PATIENTS
SO CANCER RESEARCH
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; P53; PROTOONCOGENE;
   EXPRESSION; FIBROBLASTS; RECEPTOR; CANCER; GENE; IMMORTALIZATION
AB Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression, Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702.
   BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030.
   UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030.
   UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL PEDIAT,HOUSTON,TX 77030.
   UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030.
FU NCI NIH HHS [CA53318, CA54897, N01-CO-46000]
NR 33
TC 58
Z9 58
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAY 1
PY 1995
VL 55
IS 9
BP 1963
EP 1970
PG 8
WC Oncology
SC Oncology
GA QV015
UT WOS:A1995QV01500029
PM 7728766
ER

PT J
AU GUINEE, DG
   TRAVIS, WD
   TRIVERS, GE
   DEBENEDETTI, VMG
   CAWLEY, H
   WELSH, JA
   BENNETT, WP
   JETT, J
   COLBY, TV
   TAZELAAR, H
   ABBONDANZO, SL
   PAIROLERO, P
   TRASTEK, V
   CAPORASO, NE
   LIOTTA, LA
   HARRIS, CC
AF GUINEE, DG
   TRAVIS, WD
   TRIVERS, GE
   DEBENEDETTI, VMG
   CAWLEY, H
   WELSH, JA
   BENNETT, WP
   JETT, J
   COLBY, TV
   TAZELAAR, H
   ABBONDANZO, SL
   PAIROLERO, P
   TRASTEK, V
   CAPORASO, NE
   LIOTTA, LA
   HARRIS, CC
TI GENDER COMPARISONS IN HUMAN LUNG-CANCER - ANALYSIS OF P53 MUTATIONS,
   ANTI-P53 SERUM ANTIBODIES AND C-ERBB-2 EXPRESSION
SO CARCINOGENESIS
LA English
DT Note
ID TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMA; DIPLOID HUMAN
   FIBROBLASTS; HUMAN-BREAST-CANCER; PROTEIN EXPRESSION; CIGARETTE-SMOKING;
   IMMUNE-RESPONSE; SEX-DIFFERENCES; POOR-PROGNOSIS; HPRT GENE
AB Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of p53 mutations, immunohistochemistry, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C-->T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos, c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for p53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in five of nine patients who had serum antibodies recognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypotheses regarding; gender differences in lung cancer susceptibility.
C1 NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892.
   NIH,PATHOL LAB,BETHESDA,MD 20892.
   ARMED FORCES INST PATHOL,WASHINGTON,DC 20306.
   MAYO CLIN,ROCHESTER,MN 55905.
   NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892.
NR 91
TC 116
Z9 116
U1 0
U2 0
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAY
PY 1995
VL 16
IS 5
BP 993
EP 1002
DI 10.1093/carcin/16.5.993
PG 10
WC Oncology
SC Oncology
GA QZ456
UT WOS:A1995QZ45600003
PM 7767998
ER

PT J
AU MASSEY, TE
   DEVEREUX, TR
   MARONPOT, RR
   FOLEY, JF
   ANDERSON, MW
AF MASSEY, TE
   DEVEREUX, TR
   MARONPOT, RR
   FOLEY, JF
   ANDERSON, MW
TI HIGH-FREQUENCY OF K-RAS MUTATIONS IN SPONTANEOUS AND VINYL
   CARBAMATE-INDUCED LUNG-TUMORS OF RELATIVELY RESISTANT B6CF1
   (C57BL/6JXBALB/CJ) MICE
SO CARCINOGENESIS
LA English
DT Article
ID ETHYL CARBAMATE; MOUSE LUNG; SUSCEPTIBILITY; DNA; POLYMORPHISMS;
   METABOLITE; ONCOGENES; URETHANE; EPOXIDE
AB The murine K-ras proto-oncogene is hypothesized to be a pulmonary adenoma susceptibility gene, This postulate is supported by the previous demonstration of a preference for mutation of the K-ras allele from the susceptible parent in lung tumors of A/JxC3H F1 mice, We have examined K-ras activation in control and vinyl carbamate (VC) (single dose 0.03 mu mol/g i.p.) treated B6CF1 mice, the progeny of resistant C57BL/6J and intermediately sensitive BALB/cJ parents, Thirty-four of 37 tumors from VC-treated mice and 17 of 23 from controls contained activating K-ras mutations. The spectra of mutations in codons 12 and 61 of K-ras were similar for the two groups, except that 7 tumors from VC-treated mice had A --> T transversions in the second base of codon 61; none were observed in tumors from saline-treated animals, PCR-based genotyping of first exon K-ras mutations revealed that the vast majority (15 of 18) of the mutations were in the BALB/cJ allele, Furthermore, the three tumors with mutated C57BL/6J K-ras were among the smallest tumors analyzed, These results are consistent with previous findings in other mouse hybrids showing parental bias for K-ras mutations and suggest that mutation of the allele of the susceptible parent may provide a growth advantage to the tumor.
C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709.
NR 21
TC 40
Z9 40
U1 0
U2 1
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAY
PY 1995
VL 16
IS 5
BP 1065
EP 1069
DI 10.1093/carcin/16.5.1065
PG 5
WC Oncology
SC Oncology
GA QZ456
UT WOS:A1995QZ45600013
PM 7767966
ER

PT J
AU KANG, DH
   ROTHMAN, N
   POIRIER, MC
   GREENBERG, A
   HSU, CH
   SCHWARTZ, BS
   BASER, ME
   GROOPMAN, JD
   WESTON, A
   STRICKLAND, PT
AF KANG, DH
   ROTHMAN, N
   POIRIER, MC
   GREENBERG, A
   HSU, CH
   SCHWARTZ, BS
   BASER, ME
   GROOPMAN, JD
   WESTON, A
   STRICKLAND, PT
TI INTERINDIVIDUAL DIFFERENCES IN THE CONCENTRATION OF
   1-HYDROXYPYRENE-GLUCURONIDE IN URINE AND POLYCYCLIC AROMATIC
   HYDROCARBON-DNA ADDUCTS IN PERIPHERAL WHITE BLOOD-CELLS AFTER
   CHARBROILED BEEF CONSUMPTION
SO CARCINOGENESIS
LA English
DT Article
ID COKE-OVEN WORKERS; HUMAN ENVIRONMENTAL EXPOSURE; BENZO<A>PYRENE DIOL
   EPOXIDE; FOUNDRY WORKERS; METABOLITES; LYMPHOCYTES; ENZYMES;
   BENZO(A)PYRENE; CARCINOGENESIS; ANTIBODIES
AB Biological markers of internal dose and macromolecular dose from PAHs provide a potential means of assessing environmental exposure to PAHs through inhalation, ingestion and percutaneous absorption, In this study we examined the time course and interindividual variation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretion in urine and PAH-DNA adduct formation in peripheral white blood cells (WBCs) after charbroiled (CB) beef consumption, As a marker of internal dose, 1-OHP-gluc was measured in human urine using immunoaffinity chromatography and synchronous fluorescence spectroscopy, PAH-DNA adducts were measured in WBCs by enzyme-linked immunosorbent assay (ELISA) in order to assess macromolecular dose, Ten healthy non-smoking males consumed identical amounts of CB beef on five consecutive days, Multiple blood and urine samples were collected before, during, and after the feeding period, The morning after the first day of CB beef consumption, individual urinary concentrations of 1-OHP-gluc increased 10- to 80-fold (range: 2.0-16.6 pmol/ml urine) above pre-feed baseline concentrations (0.23 +/- 0.11 pmol/ml) in the 10 subjects, 1-OHP-gluc concentration decreased to near baseline levels by 24-72 h after CB beef consumption ended, In contrast, PAH-DNA adducts in WBCs increased markedly in only four of 10 subjects during or after CB beef consumption, Significant interindividual variation was observed for both urinary 1-OHP-gluc concentration (P < 0.001 by Kruskal-Wallis) and PAH-DNA adduct levels (P < 0.005) during the feeding period, The mean urinary 1-OHP-gluc concentration for each subject during and immediately after (days 2-8) the feeding period was significantly correlated with their mean PAH-DNA adduct level in WBCs during the same time period (Spearman r = 0.79, P < 0.01), Evidence of segregation of the subjects into separate response groups based on level of urinary 1-OHP-gluc was observed, suggesting that discrete determinants may regulate the absorption, metabolism and/or excretion of ingested pyrene.
C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205.
   NCI,DIV CANC ETIOL,BETHESDA,MD 20892.
   RUTGERS STATE UNIV,DEPT ENVIRONM SCI,NEW BRUNSWICK,NJ 08903.
   MT SINAI SCH MED,DEPT COMMUNITY MED,NEW YORK,NY.
RP KANG, DH (reprint author), NIOSH,HAZARD EVALUAT & TECH ASSISTANCE BRANCH,CINCINNATI,OH 45226, USA.
RI Kang, Dae Hee/E-8631-2012
FU NIEHS NIH HHS [P01-ES06052, P30-ES03819]
NR 48
TC 115
Z9 116
U1 0
U2 9
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAY
PY 1995
VL 16
IS 5
BP 1079
EP 1085
DI 10.1093/carcin/16.5.1079
PG 7
WC Oncology
SC Oncology
GA QZ456
UT WOS:A1995QZ45600015
PM 7767968
ER

PT J
AU LINK, CJ
   EVANS, MK
   COOK, JA
   MULDOON, R
   STEVNSNER, T
   BOHR, VA
AF LINK, CJ
   EVANS, MK
   COOK, JA
   MULDOON, R
   STEVNSNER, T
   BOHR, VA
TI CAFFEINE INHIBITS GENE-SPECIFIC REPAIR OF UV-INDUCED DNA-DAMAGE IN
   HAMSTER-CELLS AND IN HUMAN XERODERMA-PIGMENTOSUM GROUP-C CELLS
SO CARCINOGENESIS
LA English
DT Article
ID COMPLEMENTATION GROUP-C; IRRADIATED HELA-CELLS; TOPOISOMERASES;
   ENHANCEMENT; AGENTS; DOMAIN; CYCLE
AB We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.
C1 NCI,DIV CANC TREATMENT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892.
   MOLEC PHARMACOL LAB,BETHESDA,MD 20892.
   NIA,GERONTOL RES CTR,MOLEC GENET LAB,BALTIMORE,MD 21224.
NR 33
TC 30
Z9 30
U1 0
U2 1
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAY
PY 1995
VL 16
IS 5
BP 1149
EP 1155
DI 10.1093/carcin/16.5.1149
PG 7
WC Oncology
SC Oncology
GA QZ456
UT WOS:A1995QZ45600025
PM 7767978
ER

PT J
AU RUBIN, JS
   BOTTARO, DP
   CHEDID, M
   MIKI, T
   RON, D
   CHEON, HG
   TAYLOR, WG
   FORTNEY, E
   SAKATA, H
   FINCH, PW
   LAROCHELLE, WJ
AF RUBIN, JS
   BOTTARO, DP
   CHEDID, M
   MIKI, T
   RON, D
   CHEON, HG
   TAYLOR, WG
   FORTNEY, E
   SAKATA, H
   FINCH, PW
   LAROCHELLE, WJ
TI KERATINOCYTE GROWTH-FACTOR
SO CELL BIOLOGY INTERNATIONAL
LA English
DT Review
ID FACTOR RECEPTOR GENES; MESENCHYMAL EPITHELIAL INTERACTIONS;
   LIGAND-BINDING SPECIFICITY; HIGH-AFFINITY RECEPTOR; FIBROBLAST GROWTH;
   FACTOR FAMILY; EXPRESSION; CELLS; CLONING; HEPARIN
AB Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex sterorid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis.
C1 TECHNION ISRAEL INST TECHNOL,IL-32000 HAIFA,ISRAEL.
   CUNY MT SINAI SCH MED,RUTTENBERG CANC CTR,NEW YORK,NY 10029.
RP RUBIN, JS (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892, USA.
RI Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
NR 75
TC 228
Z9 233
U1 0
U2 3
PU ACADEMIC PRESS (LONDON) LTD
PI LONDON
PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX
SN 1065-6995
J9 CELL BIOL INT
JI Cell Biol. Int.
PD MAY
PY 1995
VL 19
IS 5
BP 399
EP 411
DI 10.1006/cbir.1995.1085
PG 13
WC Cell Biology
SC Cell Biology
GA RH848
UT WOS:A1995RH84800006
PM 7640656
ER

PT J
AU AVIS, I
   MATHIAS, A
   UNSWORTH, EJ
   MILLER, MJ
   CUTTITTA, F
   MULSHINE, JL
   JAKOWLEW, SB
AF AVIS, I
   MATHIAS, A
   UNSWORTH, EJ
   MILLER, MJ
   CUTTITTA, F
   MULSHINE, JL
   JAKOWLEW, SB
TI ANALYSIS OF SMALL-CELL LUNG-CANCER CELL-GROWTH INHIBITION BY
   13-CIS-RETINOIC ACID - IMPORTANCE OF BIOAVAILABILITY
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Article
ID CHICK LIMB BUD; RETINOL-BINDING PROTEIN; VITAMIN-A; RECEPTOR-BETA;
   DIFFERENTIAL EXPRESSION; NUCLEAR RECEPTORS; IDENTIFICATION; METABOLISM;
   PREVENTION; CARCINOMA
AB 13-cis-Retinoic acid can mediate differentiation of transformed cells and slow the proliferation of malignant cells, suggesting its use as a potential intervention tool. Specific cDNA probes for retinoic acid receptors demonstrated the expression of mRNAs for the different retinoic acid receptor isoforms in small cell lung cancer cell lines. Addition of 13-cis-retinoic acid to small cell lung cancer cells cultured using serum-free, hormonally defined medium resulted in a 5-8-fold increase in the level of the retinoic acid receptor-beta mRNAs; in medium containing serum, the increase in expression of the retinoic acid receptor-beta mRNAs was less pronounced, usually no more than 2-fold. Using an in vitro proliferation assay, addition of 13-cis-retinoic acid resulted in a significant dose-dependent, growth-inhibitory effect on the small cell lung cancer cell lines tested using serum-free conditions. These inhibitory effects decreased when cells were cultured in medium containing serum or serum components. Molecular size exclusion chromatography and native gel electrophoresis showed that the causative serum component eluted and migrated with serum albumin. Preincubating serum with triglycerides restored the inhibitory effects of 13-cis-retinoic acid demonstrated in serum-free systems. These data suggest that 13-cis-retinoic acid preferentially binds to serum albumin, restricting its inhibitory effects on epithelial cell receptors. Blocking retinoic acid-albumin interactions with a fatty acid source may improve the bioavailability of 13-cis-retinoic acid and significantly enhance the inhibitory effect in vivo.
C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850.
NR 62
TC 36
Z9 36
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD MAY
PY 1995
VL 6
IS 5
BP 485
EP 492
PG 8
WC Cell Biology
SC Cell Biology
GA QX811
UT WOS:A1995QX81100001
PM 7647031
ER

PT J
AU SMITH, GH
   GALLAHAN, D
   DIELLA, F
   JHAPPAN, C
   MERLINO, G
   CALLAHAN, R
AF SMITH, GH
   GALLAHAN, D
   DIELLA, F
   JHAPPAN, C
   MERLINO, G
   CALLAHAN, R
TI CONSTITUTIVE EXPRESSION OF A TRUNCATED INT3 GENE IN MOUSE MAMMARY
   EPITHELIUM IMPAIRS DIFFERENTIATION AND FUNCTIONAL-DEVELOPMENT
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Article
ID CELL-CYCLE CONTROL; TUMOR VIRUS; CONTROL PROTEINS; NOTCH-GENE; GLAND;
   REGION; LIN-12; TUMORIGENESIS; ACTIVATION; HOMOLOGY
AB INT3 is interrupted by retroviral DNA insertion in approximately 18% of primary Czech mouse mammary tumors induced by mouse mammary tumor virus. One consequence of these insertions is the production of a 2.4-kilobase, tumor-specific RNA transcript encoding the entire intracellular domain of the Int3 protein which is initiated from the 3' long terminal repeat promoter of the inserted viral genome. Female mice (FVB-3) transgenic for a genomic fragment comprised of this truncated region of INT3 express the 2.4-kilobase truncated INT3 transcript and exhibit focal mammary tumors at 100% penetrance. INT3 is a member of a family of genes, highly conserved through evolution and characterized by Drosophila melanogaster Notch and Caenorhabditis elegans lin-12, the function of which relates to cell fate determination. Upon transfection into the appropriate hosts, expression vectors of truncated Notch and lin-12, representing their respective cytoplasmic domains, have been demonstrated to effect their complete gene function with respect to cell fate determination. This suggests that the extracellular portion of these proteins function only to regulate activity. Reciprocal transplantation of transgenic FVB-3 and normal mammary tissue to the epithelium-divested fat pads of the respective donor females demonstrates that FVB-3 mammary epithelium is unable to grow and/or to functionally differentiate. However, normal epithelium grows and fully differentiates in transgenic FVB-3 fat pads, indicating that the dysfunction of FVB-3 mammary glands is due to a deficiency inherent in their epithelium. Electron microscopy reveals that transgenic INT3 epithelial cells do not form intercellular junctional complexes in the developing subadult mammary gland. The hormonal stimulation of pregnancy overcomes the deficiency for ductal growth so apparent in the virgin gland such that pregnant FVB-3 glands produce complete ductal systems. Nevertheless, during pregnancy, FVB-3 mammary cells fail to form secretory lobules and to produce milk. Examination of INT3 expression by immunocytochemistry and reverse transcriptase-PCR show that INT3 is expressed constitutively in mammary stroma and epithelia at all stages of postpubertal mammary evolution. These results indicate that deregulated expression of a truncated Int3 in mammary epithelial cells limits their capacity to perform the cell fate decisions required for morphogenesis and functional differentiation.
C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892.
RP SMITH, GH (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA.
NR 38
TC 82
Z9 85
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD MAY
PY 1995
VL 6
IS 5
BP 563
EP 577
PG 15
WC Cell Biology
SC Cell Biology
GA QX811
UT WOS:A1995QX81100010
PM 7544153
ER

PT J
AU MONTANO, X
   JIMENEZ, A
AF MONTANO, X
   JIMENEZ, A
TI INTRACELLULAR EXPRESSION OF THE MONOCLONAL ANTI-RAS ANTIBODY Y13-259
   BLOCKS THE TRANSFORMING ACTIVITY OF RAS ONCOGENES
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Article
ID NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; HEAVY-CHAIN; SENSE RNA; PROTEIN;
   CELLS; GENE; IMMUNOGLOBULIN; SECRETION; EPITOPE
AB Microinjection of the anti-ras antibody Mab Y13-259 modifies ras function and can induce temporary reversion of the transformed phenotype in mutant ras-transformed cells. Intracellular production of neutralizing antibodies represents an approach to investigate the regulation of gene function. The genes coding for the heavy and light chains of Mab Y13-259 were isolated from a cDNA library. NIH3T3 cells transfected with heavy and light chain expression vectors produced functional anti-ras antibody. The production of functional antibody did not require glycosylation.
   To ensure that the antibody entered the cytoplasm and not the secretory pathway, the hydrophobic leader sequences of both chains were removed and replaced with synthetic initiator sequences. The modified heavy chain gene was cloned under the control of the murine sarcoma virus long terminal repeat, and the light chain gene under the control of the mouse mammary tumor virus long terminal repeat, which allows the induction of light chain expression in the presence of dexamethasone. When both heavy and light chain genes were expressed in cells with activated ras (morphologically transformed) in the presence of dexamethasone, we observed phenotypic reversion to characteristics of nontransformed cells. These experiments show that intracellular expression of antibodies can also be used as an alternative to analyze biological functions of a given protein.
C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543.
   NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701.
NR 40
TC 17
Z9 19
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD MAY
PY 1995
VL 6
IS 5
BP 597
EP 605
PG 9
WC Cell Biology
SC Cell Biology
GA QX811
UT WOS:A1995QX81100013
PM 7647040
ER

PT J
AU WEI, LN
   LEE, CH
   CHINPAISAL, C
   COPELAND, NG
   GILBERT, DJ
   JENKINS, NA
   HSU, YC
AF WEI, LN
   LEE, CH
   CHINPAISAL, C
   COPELAND, NG
   GILBERT, DJ
   JENKINS, NA
   HSU, YC
TI STUDIES OF CLONING, CHROMOSOMAL MAPPING, AND EMBRYONIC EXPRESSION OF THE
   MOUSE RAB GERANYLGERANYL TRANSFERASE BETA-SUBUNIT
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Article
ID STEM-CELLS; DIFFERENTIATION
AB The mouse Rab geranylgeranyl transferase beta subunit has been cloned from a mouse E8.5 embryonic cDNA library. Sequence comparison reveals 97.4% sequence identity at the amino acid level to the rat clone isolated from an adult rat brain cDNA library. This gene, given a gene symbol of Rabggtb, is mapped in the distal region of mouse chromosome 3. It is ubiquitously expressed in adult animals but displays an interesting pattern of expression during a specific time of embryonic development. The expression of this gene can be detected in the whole embryos during early embryonic stages and is specifically concentrated in the developing brain, heart, and liver between gestation stages of E11.5 and E13.5. In addition, the expression of this gene is induced by retinoic acid in a mouse embryonal carcinoma cell line, P19.
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702.
   JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218.
RP WEI, LN (reprint author), UNIV MINNESOTA,DEPT PHARMACOL,3-249 MILLARD HALL,435 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA.
FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD20347]; NIDDK NIH HHS
   [DK46866-01]
NR 20
TC 6
Z9 7
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD MAY
PY 1995
VL 6
IS 5
BP 607
EP 614
PG 8
WC Cell Biology
SC Cell Biology
GA QX811
UT WOS:A1995QX81100014
PM 7544156
ER

PT J
AU PUTNAM, FW
   HELMERS, K
   HOROWITZ, LA
AF PUTNAM, FW
   HELMERS, K
   HOROWITZ, LA
TI HYPNOTIZABILITY AND DISSOCIATIVITY IN SEXUALLY ABUSED GIRLS
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE SEXUAL ABUSE; DISSOCIATION; HYPNOSIS
ID POSTTRAUMATIC-STRESS-DISORDER; MULTIPLE PERSONALITY-DISORDER; CHILDHOOD;
   PSYCHOPATHOLOGY; EXPERIENCES; VALIDITY; CHILDREN; SCALE
AB Research on the relation between hypnotizability and clinical dissociation has led to contradictory findings.  Measures of hypnotizability and dissociation are only weakly correlated in general population samples, but studies of posttraumatic stress and dissociative disorders patients have found elevated levels of clinical dissociation and hypnotizability respectively.  This study assesses the relationships among hypnotizability, clinical dissociation and traumatic antecedents in 54 sexually abused girls, ages 6-15 years, and 51 matched controls.  Hypnotizability was assessed on initial evaluation and again in matched subsamples at one year using the Stanford Hypnotic Clinical Scale for Children.  Clinical dissociation was assessed using the Child Dissociative Checklist.  Abuse variables were extracted from Child Protective Services reports.  There were no significant differences in hypnotizability between abuse and control subjects.  There were significant differences in clinical dissociation initially and on 1-year retest.  Hypnotizability and clinical dissociation were only weakly correlated (r(105) = .118, p = NS).  However, in the abuse group, highly hypnotizable subjects were significantly more dissociative.  Higher levels of clinical dissociation were associated with abuse by multiple perpetrators and co-presence of physical abuse independent of the sexual abuse.  A small subgroup of ''double dissociative'' subjects, high in both hypnotizability and dissociativity, was identified.  Double dissociation was associated with multiple perpetrators and earlier onset of sexual abuse.
C1 UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089.
RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 37
TC 32
Z9 32
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abus. Negl.
PD MAY
PY 1995
VL 19
IS 5
BP 645
EP 655
DI 10.1016/0145-2134(95)00022-Z
PG 11
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA QW202
UT WOS:A1995QW20200011
PM 7664143
ER

PT J
AU HOUSEAL, TW
   COOK, JA
   MODI, WS
   HALE, DW
AF HOUSEAL, TW
   COOK, JA
   MODI, WS
   HALE, DW
TI IDENTIFICATION OF HIGHLY CONSERVED LOCI BY GENOME PAINTING
SO CHROMOSOME RESEARCH
LA English
DT Article
DE FLUORESCENCE IN SITU HYBRIDIZATION; GENOMIC DNA; MOLECULAR EVOLUTION;
   REPETITIVE DNA; RODENT
ID INSITU SUPPRESSION HYBRIDIZATION; MOUSE SATELLITE DNA; CHROMOSOMAL
   LOCALIZATION; MICROTUS-CHROTORRHINUS; NUCLEOTIDE-SEQUENCE; PARENTAL
   GENOMES; GUINEA-PIG; EVOLUTION; HYBRID; AMPLIFICATION
AB Fluorescence in situ hybridization was used to identify patterns of DNA similarity among the genomes of several rodent taxa. Total genomic or Cot-1 DNAs were used as hybridization probes against metaphase preparations across different taxonomic levels, including three species of Microtus (suborder Sciurognathi), Mus musculus (suborder Sciurognathi) and Ctenomys steinbachi (suborder Hystricognathi). The hybridization patterns of Mus or Peromyscos (sciurognath) DNA to Mus metaphases, which were consistent with what is known of the satellite sequences in these species, demonstrated the efficacy of this approach for molecular cytogenetics and evolutionary biology. Additional hybridizations to chromosomes of Ctenomys or Microtus identified loci consisting of highly conserved DNA sequences. This approach has proved useful in investigating genome homologies across divergent rodent lineages. Chromosome microdissection can be used to characterize these regions further.
C1 UNIV ALASKA FAIRBANKS,FAIRBANKS,AK 99775.
   NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702.
   YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520.
RP HOUSEAL, TW (reprint author), INTEGRATED GENET INC,1 MT RD,FRAMINGHAM,MA 01701, USA.
OI Cook, Joseph/0000-0003-3985-0670
NR 39
TC 6
Z9 6
U1 0
U2 3
PU RAPID SCIENCE PUBLISHERS
PI LONDON
PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH
SN 0967-3849
J9 CHROMOSOME RES
JI Chromosome Res.
PD MAY
PY 1995
VL 3
IS 3
BP 175
EP 181
DI 10.1007/BF00710711
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA QR612
UT WOS:A1995QR61200005
PM 7780661
ER

PT J
AU CLARKE, K
   VEECH, RL
AF CLARKE, K
   VEECH, RL
TI METABOLIC COMPLEXITIES IN CARDIAC IMAGING
SO CIRCULATION
LA English
DT Editorial Material
DE IMAGING; EDITORIALS; METABOLISM
ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; GLUCOSE-6-PHOSPHATASE
   ACTIVITY; REPERFUSED MYOCARDIUM; LUMPED CONSTANT; BRAIN; HEART; INSULIN;
   RAT; SKELETAL
C1 NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852.
   UNIV OXFORD,DEPT BIOCHEM,OXFORD OX1 3QU,ENGLAND.
NR 29
TC 7
Z9 7
U1 0
U2 0
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 1
PY 1995
VL 91
IS 9
BP 2299
EP 2301
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QV251
UT WOS:A1995QV25100002
PM 7729013
ER

PT J
AU CARACCIOLO, EA
   DAVIS, KB
   SOPKO, G
   KAISER, GC
   CORLEY, SD
   SCHAFF, H
   TAYLOR, HA
   CHAITMAN, BR
AF CARACCIOLO, EA
   DAVIS, KB
   SOPKO, G
   KAISER, GC
   CORLEY, SD
   SCHAFF, H
   TAYLOR, HA
   CHAITMAN, BR
TI COMPARISON OF SURGICAL AND MEDICAL GROUP SURVIVAL IN PATIENTS WITH LEFT
   MAIN CORONARY-ARTERY DISEASE - LONG-TERM CASS EXPERIENCE
SO CIRCULATION
LA English
DT Article
DE CORONARY DISEASE; BYPASS; SURGERY
ID CONGESTIVE-HEART-FAILURE; SEVERE ANGINA-PECTORIS; 10-YEAR FOLLOW-UP;
   BYPASS-SURGERY; ANGIOGRAPHIC PREDICTORS; MYOCARDIAL-INFARCTION;
   OPERATIVE MORTALITY; TREATED PATIENTS; STENOSIS; REGISTRY
AB Background Observational and randomized studies designed to compare surgical and medical therapies in patients with left main coronary artery disease (LMCD) have shown that coronary artery bypass graft (CABG) surgery prolongs life in most patients with LMCD. The present report of 1484 patients with LMCD in the Coronary Artery Surgery Study (CASS) Registry extends the originally published 5-year surgical and medical group survival analysis to more than 16 years of follow-up and permits analysis of LMCD patient subgroups.
   Methods and Results The CASS Registry contains 1484 patients with greater than or equal to 50% left main coronary artery stenosis initially treated with either surgical or nonsurgical therapy. The 15-year cumulative survival estimates were 37% for the 1153 patients in the surgical group compared with 27% for the 331 patients in the medical group. Median survival in the surgical group was 13.3 years (12.8 to 13.8 years, 95% confidence limits) compared with only 6.6 years (5.4 to 7.9 years) in the medical group (difference, 6.7 years; P<.0001). Median survival was also significantly longer in the surgical group stratified by age, sex, anginal class, left ventricular (LV) function, coronary anatomy, and the extent of LMCD. However, CABG surgery did not significantly prolong median survival in patient subgroups with (1) Left main coronary stenosis of 50% to 59%; (2) normal LV systolic function; (3) normal or mildly abnormal LV systolic function and a right coronary artery stenosis greater than or equal to 70%; and (4) a nonstenotic (less than or equal to 70%) right coronary artery. The 15-year cumulative survival for patients with normal LV systolic function in the surgical and medical groups was 42% and 51%, respectively. Median survival was 14.7 years in the surgical group and >15 years in the medical group (P=NS). In patients with normal LV systolic function and a right coronary artery stenosis greater than or equal to 70%, the 15-year cumulative survival rates were also similar in the surgical and medical groups (40% and 48%, respectively). Median survival was 14.3 years in the surgical group and 14.2 years in the medical group (P=NS). The 15-year cumulative survival estimates for all subgroups were affected by convergence of the surgical and medical survival group curves owing to a disproportionate increase in the late surgical group mortality. Overall, 25% of patients in the medical group ultimately underwent CABG surgery. Lf all medical group patients had survived long enough, about 47% would be estimated to have had surgery by 15 years.
   Conclusions This report, which extends follow-up of more than 16 years in CASS Registry patients with LMCD, shows that CABG surgery prolongs life in most clinical acid angiographic subgroups. However, median survival was not prolonged by CABG surgery in patients with normal LV systolic function, even if a significant right coronary artery stenosis (greater than or equal to 70%) also was present. These results extend our understanding of the natural history of LMCD and permit a more accurate estimate of long-term surgical and medical group survival.
C1 UNIV WASHINGTON,CASS COORDINATING CTR,SEATTLE,WA 98105.
   ST LOUIS UNIV,HLTH SCI CTR,ST LOUIS,MO.
   NHLBI,BETHESDA,MD 20892.
   MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905.
   UNIV ALABAMA,MED CTR,BIRMINGHAM,AL 35294.
OI Schaff, Hartzell/0000-0003-0994-027X
NR 64
TC 202
Z9 218
U1 1
U2 3
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 1
PY 1995
VL 91
IS 9
BP 2325
EP 2334
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QV251
UT WOS:A1995QV25100008
PM 7729018
ER

PT J
AU CARACCIOLO, EA
   DAVIS, KB
   SOPKO, G
   KAISER, GC
   CORLEY, SD
   SCHAFF, H
   TAYLOR, HA
   CHAITMAN, BR
AF CARACCIOLO, EA
   DAVIS, KB
   SOPKO, G
   KAISER, GC
   CORLEY, SD
   SCHAFF, H
   TAYLOR, HA
   CHAITMAN, BR
TI COMPARISON OF SURGICAL AND MEDICAL GROUP SURVIVAL IN PATIENTS WITH LEFT
   MAIN EQUIVALENT CORONARY-ARTERY DISEASE - LONG-TERM CASS EXPERIENCE
SO CIRCULATION
LA English
DT Article
DE CORONARY DISEASE; BYPASS; SURGERY
ID CONGESTIVE-HEART-FAILURE; SEVERE ANGINA-PECTORIS; BYPASS-SURGERY;
   MYOCARDIAL-INFARCTION; TREATED PATIENTS; ANGIOGRAPHIC PREDICTORS;
   OPERATIVE MORTALITY; NATURAL-HISTORY; EXERCISE TEST; FOLLOW-UP
AB Background Combined severe proximal left anterior descending and proximal left circumflex coronary artery disease, or left main equivalent (LMEQ) disease, defines a prognostic high-risk angiographic subset of patients with chronic ischemic heart disease. While numerous observational and randomized clinical trials showed prolonged survival in surgically compared with medically treated patients with left main coronary artery disease, relatively few observational studies compared surgical and medical therapies in patients with LMEQ disease. The present report of 912 patients with LMEQ disease in the Coronary Artery Surgery Study (CASS) Registry extends the originally published 5-year surgical and medical group survival analysis to more than 16 years of follow-up and permits analysis of LMEQ patient subgroups.
   Methods and Results The CASS Registry contains 912 patients with LMEQ disease, defined as combined stenoses of greater than or equal to 70% in the proximal left anterior descending coronary artery before the first septal perforator and proximal circumflex coronary artery before the first obtuse marginal branch, initially treated with either surgical or nonsurgical therapy. The 15-year cumulative survival estimates were 44% for the 630 patients in the surgical group and 31% for the 282 patients in the medical group. Median survival in the surgical group was 13.1 years (12.7 to 14.1 years, 95% confidence limits) compared with only 6.2 years (4.8 to 7.9 years) in the medical group (difference, 6.9 years; P<.0001). Median survival was also significantly longer in the surgical group stratified by age, sex, anginal class, left ventricular (LV) function, and coronary anatomy. However, coronary artery bypass graft (CABG) surgery did not significantly prolong median survival in patient subgroups with (1) normal LV systolic function, even if a significant right coronary artery stenosis (greater than or equal to 70%) also was present, and (2) mildly abnormal (LV score, 6 to 10) LV systolic function. The 15-year cumulative survival in patients with normal LV systolic function in the surgical and medical groups was 63% and 54%, respectively. Median survival was >15 years in both the surgical and medical groups (P=NS). In patients with normal LV systolic function and right coronary artery stenosis greater than or equal to 70%, the 15-year cumulative survival was also similar in the surgical and medical groups (63% and 53%, respectively). Median survival was >15 years in both the surgical and medical groups (P=NS). The 15-year cumulative survival estimates in all subgroups were affected by convergence of the surgical and medical group survival curves caused by a disproportionate increase in late surgical group mortality. Overall, 26% of patients in the medical group ultimately underwent CABG surgery. If all medical group patients had survived long enough, about 65% would be estimated to have had surgery by 15 years. When the CASS Registry patients with LMEQ disease who participated in the randomized trial or who were randomizable were analyzed, CABG surgery did not prolong the 15-year cumulative survival estimates compared with nonsurgical therapy for randomized (71% versus 67%, respectively) and for randomizable patients (62% versus 92%, respectively) with an LV ejection fraction greater than or equal to 50%.
   Conclusions This report, which extends follow-up of more than 16 years in CASS Registry patients with LMEQ disease, shows that CABG surgery prolongs life in most clinical and angiographic subgroups. However, median survival was not prolonged by CABG surgery in patients with normal LV systolic function, even if a significant right coronary artery stenosis (greater than or equal to 70%) also was present or in patients with an LV ejection fraction greater than or equal to 50% who participated in the CASS randomized trial or who were randomizable. These results extend our understanding of the natural history of LMEQ disease and permit a more accurate estimate of long-term surgical and medical group survival. These long-term results should allow clinicians to make more informed decisions about the best choice of treatment available for patients with similar clinical and angiographic features.
C1 UNIV WASHINGTON,CASS COORDINATING CTR,SEATTLE,WA 98105.
   ST LOUIS UNIV,HLTH SCI CTR,ST LOUIS,MO.
   NHLBI,BETHESDA,MD 20892.
   MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905.
   UNIV ALABAMA,MED CTR,BIRMINGHAM,AL 35294.
OI Schaff, Hartzell/0000-0003-0994-027X
NR 67
TC 122
Z9 133
U1 0
U2 0
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 1
PY 1995
VL 91
IS 9
BP 2335
EP 2344
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QV251
UT WOS:A1995QV25100009
PM 7729019
ER

PT J
AU SCHULICK, AH
   NEWMAN, KD
   VIRMANI, R
   DICHEK, DA
AF SCHULICK, AH
   NEWMAN, KD
   VIRMANI, R
   DICHEK, DA
TI IN-VIVO GENE-TRANSFER INTO INJURED CAROTID ARTERIES - OPTIMIZATION AND
   EVALUATION OF ACUTE TOXICITY
SO CIRCULATION
LA English
DT Article
DE GENES; CAROTID ARTERIES; MUSCLE, SMOOTH; VIRUSES
ID THERAPY; VECTORS; CELLS
AB Background Adenoviral vectors are very attractive agents for use in in vivo arterial gene transfer. In a previous study, we demonstrated high-efficiency adenovirus-mediated gene transfer into medial smooth muscle cells of balloon-injured rat carotid arteries. We now further characterize this system by investigating the reproducibility of recombinant gene expression, the presence of acute adenovirus-associated toxicity in the vessel wall, and the optimal virus concentration for transduction.
   Methods and Results Balloon-injured rat carotid arteries were incubated with (1) an adenovirus expressing a P-galactosidase gene (Av1LacZ4), (2) a related adenovirus without the recombinant gene (Add1312), or (3) control solutions. Recombinant gene expression was determined 3 days after gene transfer by measurement of beta-galactosidase activity in vessel extracts and by counting of smooth muscle cells in microscopic sections that were histochemically stained to detect recombinant beta-galactosidase activity. Adenovirus-associated toxicity was assessed in microscopic cross sections by counting of total smooth muscle cell nuclei in the media (to identify cell loss) and characterization of medial cellular infiltrates with histochemical stains for specific inflammatory cells (neutrophils, lymphocytes, macrophages, and monocytes). Maximum recombinant gene expression after incubation with Av1LacZ4 was produced by virus concentrations ranging from 2x10(10) to 5x10(10) plaque-forming units (pfu)/mL. Surprisingly, use of a higher concentration of Av1LacZ4 virus (1x10(11) pfu/ml) resulted in loss of recombinant gene expression. In addition, infusion of either Av1LacZ4 or Add1312 at 1x10(11) pfu/mL resulted in statistically significant decreases in medial smooth muscle cell number (53% decrease, P<0.01 for Av1LacZ4; 39% decrease, P<.05 for Addl312) compared with vessels infused with control solution. This decrease in smooth muscle cell number was not present after the infusion of virus at lower concentrations. The number of neutrophils in vessel cross sections was significantly increased (fivefold; P<.05) after infusion of Av1LacZ4 at 1X10(11) pfu/ml compared with vessels infused with control solution. Lymphocytes, macrophages, and monocytes were present only in low numbers in all vessel cross sections and were not increased consequent to adenovirus infusion.
   Conclusions This model of focal in vivo adenovirus-mediated gene transfer into the media of injured arteries is highly reproducible and allows high-level recombinant gene expression over a fairly narrow range of virus concentrations. Acute adenovirus-associated tissue toxicity, as demonstrated by medial smooth muscle cell loss and neutrophilic infiltrates, places an upper limit on virus concentration and associated recombinant gene expression and suggests the presence of a ''window'' of virus concentration in which either therapeutic or biological effects of recombinant genes can be studied in the absence of associated acute toxicity.
C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892.
   ARMED FORCES INST PATHOL,DIV CARDIOVASC PATHOL,WASHINGTON,DC 20306.
NR 28
TC 104
Z9 106
U1 0
U2 0
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAY 1
PY 1995
VL 91
IS 9
BP 2407
EP 2414
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA QV251
UT WOS:A1995QV25100018
PM 7729028
ER

PT J
AU SCHACHTNER, SK
   ROME, JJ
   HOYT, RF
   NEWMAN, KD
   VIRMANI, R
   DICHEK, DA
AF SCHACHTNER, SK
   ROME, JJ
   HOYT, RF
   NEWMAN, KD
   VIRMANI, R
   DICHEK, DA
TI IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER VIA THE PULMONARY-ARTERY OF
   RATS
SO CIRCULATION RESEARCH
LA English
DT Article
DE PULMONARY ARTERY; PULMONARY HYPERTENSION; GENE TRANSFER; GENE THERAPY;
   ADENOVIRUS
ID CONGENITAL HEART-DEFECTS; ELASTOLYTIC ACTIVITY; CYSTIC-FIBROSIS;
   HYPERTENSION; EXPRESSION; LUNG; ENDOTHELIN-1; DISEASE; INVIVO;
   PATHOGENESIS
AB Gene transfer into the pulmonary vasculature has the potential to be a powerful technique for both investigation of pulmonary pathophysiology and development of genetic therapies for pulmonary vascular disease. To evaluate the potential for in vivo pulmonary arterial gene transfer, we infused adenoviral vectors into the left pulmonary artery of Sprague-Dawley and cotton rats. Access to the left pulmonary artery was obtained by a percutaneous transcatheter approach or through thoracotomy and pulmonary arteriotomy. With the thoracotomy approach, both pulmonary arterial inflow and pulmonary venous outflow were occluded during vector infusion and throughout a subsequent 20-minute dwell period. The success of gene transfer was assessed by staining for evidence of recombinant gene expression in lungs excised at lime points ranging from 48 to 72 hours after virus infusion. With the thoracotomy technique, pulmonary gene transfer was successful in 15% of surviving Sprague-Dawley rats and 30% of surviving cotton rats. Percutaneous catheter-based pulmonary gene transfer was not successful. In rats with pulmonary gene transfer, 1% to 8% of total left lung cells expressed the recombinant gene. Recombinant gene expression was found in endothelial cells (0.2% to 18% of total transduced cells), smooth muscle cells (0% to 3%), macrophages (1% to 7%), airway epithelial cells (2% to 50%), and alveolar epithelial cells (38% to 94%). Investigation of the low rate of successful gene transfer in individual animals suggested that insufficient physical contact between the virions and pulmonary cells was the most likely cause. In vivo gene transfer into the rat pulmonary vasculature can be accomplished with adenovirus vectors. The overall efficiency is low, however, and pulmonary arterial infusion of the vectors results in gene transfer primarily into nonvascular cells.
C1 ARMED FORCES INST PATHOL,CARDIOVASC SECT,WASHINGTON,DC 20306.
   NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892.
   NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892.
   CHILDRENS NATL MED CTR,DEPT CARDIOL,WASHINGTON,DC 20010.
   CHILDRENS NATL MED CTR,DEPT SURG,WASHINGTON,DC 20010.
NR 49
TC 43
Z9 43
U1 0
U2 0
PU AMER HEART ASSOC
PI DALLAS
PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD MAY
PY 1995
VL 76
IS 5
BP 701
EP 709
PG 9
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
   Disease
SC Cardiovascular System & Cardiology; Hematology
GA QU898
UT WOS:A1995QU89800002
PM 7728986
ER

PT J
AU CERRUTI, C
   SHENG, P
   LADENHEIM, B
   EPSTEIN, CJ
   CADET, JL
AF CERRUTI, C
   SHENG, P
   LADENHEIM, B
   EPSTEIN, CJ
   CADET, JL
TI INVOLVEMENT OF OXIDATIVE AND L-ARGININE-NO PATHWAYS IN THE NEUROTOXICITY
   OF DRUGS OF ABUSE IN-VITRO
SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
LA English
DT Article; Proceedings Paper
CT IUPHAR 1994 Satellite Symposium on In Vitro Neurotoxicology
CY JUL, 1994
CL VAL MORIN, CANADA
DE METHAMPHETAMINE; METHYLENEDIOXYMETAMPHETAMINE; NITRIC OXIDE SYNTHASE;
   OXIDATIVE STRESS; PRIMARY CULTURES; SUPEROXIDE DISMUTASE-TRANSGENIC MICE
AB 1. Inhibitors of nitric oxide (NO) formation or ADP-ribosylation attenuate methamphetamine (METH)- and methylenedioxymetamphetamine (MDMA)-induced neurotoxicity on dopaminergic and serotonergic cells in primary cultures.
   2. They also prevent METH-induced reactive gliosis in dopaminergic cultures.
   3. Overexpression of superoxide dismutase (SOD) in cells obtained from SOD-transgenic mice also attenuates drug-induced toxicity.
   4. These data indicate a role for oxygen-based and NO free radicals in the mechanisms of cell death associated with drugs of abuse in vitro.
C1 NIDA,DIV INTRAMURAL RES,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224.
   UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA.
NR 4
TC 26
Z9 27
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL AUSTR
PI CARLTON
PA 54 UNIVERSITY ST, P O BOX 378, CARLTON 3053, AUSTRALIA
SN 0305-1870
J9 CLIN EXP PHARMACOL P
JI Clin. Exp. Pharmacol. Physiol.
PD MAY
PY 1995
VL 22
IS 5
BP 381
EP 382
DI 10.1111/j.1440-1681.1995.tb02025.x
PG 2
WC Pharmacology & Pharmacy; Physiology
SC Pharmacology & Pharmacy; Physiology
GA RA297
UT WOS:A1995RA29700018
PM 7554438
ER

PT J
AU Merajver, SD
   Frank, TS
   Xu, JZ
   Pham, TM
   Calzone, KA
   BennettBaker, P
   Chamberlain, J
   Boyd, J
   Garber, JE
   Collins, FS
   Weber, BL
AF Merajver, SD
   Frank, TS
   Xu, JZ
   Pham, TM
   Calzone, KA
   BennettBaker, P
   Chamberlain, J
   Boyd, J
   Garber, JE
   Collins, FS
   Weber, BL
TI Germline BRCA1 mutations and loss of the wild-type allele in tumors from
   families with early onset breast and ovarian cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENETIC-ANALYSIS; CHROMOSOME-17Q21; LINKAGE; REGION
AB The BRCA1 gene on human chromosome 17q21 is responsible for an autosomal dominant syndrome of inherited early onset breast/ovarian cancer, It is estimated that women harboring a germline BRCA1 mutation incur an 85% lifetime risk of breast cancer and a greatly elevated risk of ovarian cancer. The BRCA1 gene has recently been isolated and mutations have been found in the germline of affected individuals in linked families. Previous studies of loss of heterozygosity (LOH) in breast tumors have been carried out on sporadic tumors derived from individuals without known linkage to BRCA1 and on tumors from linked families, Loss of large regions of chromosome 17 has been observed, but these LOH events could not be unequivocally ascribed to BRCA1.
   We have studied 28 breast and 6 ovarian tumors from families with strong evidence for linkage between breast cancer and genetic markers flanking BRCA1. These tumors were examined for LOH using genetic markers flanking and within BRCA1, including THRA1, D17S856, EDH17B1, EDH17B2, and D17S183, Forty-six percent (16/34) of tumors exhibit LOH which includes BRCA1, In 8 of 16 tumors the parental origin of the deleted allele could be determined by evaluation of haplotypes of associated family members; in 100% of these cases, the wild-type allele was lost. In some of these families germline mutations in BRCA1 have been determined; analyses of tumors with LOH at BRCA1 have revealed that only the disease-related allele of BRCA1 was present. These data strongly support the hypothesis that BRCA1 is a tumor suppressor gene.
C1 DANA FARBER CANC INST,BOSTON,MA 02115.
   NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892.
   UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104.
   UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104.
   UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104.
   UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109.
   UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109.
   UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109.
RP Merajver, SD (reprint author), UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,5510 MSRB I,ANN ARBOR,MI 48109, USA.
FU NCI NIH HHS [R01 CA57601-01]; NCRR NIH HHS [3MO1RR00042-34S1]; NHGRI NIH
   HHS [P30 HG00209]
NR 23
TC 68
Z9 71
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W.,
   PHILADELPHIA, PA 19106
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY
PY 1995
VL 1
IS 5
BP 539
EP 544
PG 6
WC Oncology
SC Oncology
GA TL080
UT WOS:A1995TL08000009
PM 9816013
ER

PT J
AU SPOONER, KM
   LANE, HC
   MASUR, H
AF SPOONER, KM
   LANE, HC
   MASUR, H
TI ANTIRETROVIRAL THERAPY - REFERENCE GUIDE TO MAJOR CLINICAL-TRIALS IN
   PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Note
ID AIDS-RELATED COMPLEX; COMBINATION THERAPY; ZIDOVUDINE THERAPY; CUBIC
   MILLIMETER; HIV-1 INFECTION; DOUBLE-BLIND; DIDEOXYCYTIDINE; DIDANOSINE;
   EFFICACY; SAFETY
C1 NIAID,BETHESDA,MD 20892.
   CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD.
NR 25
TC 2
Z9 2
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY
PY 1995
VL 20
IS 5
BP 1145
EP 1151
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA QY771
UT WOS:A1995QY77100009
PM 7619990
ER

PT J
AU ABRAMSON, MA
   DIETZE, R
   FRUCHT, DM
   SCHWANTZ, R
   KENNEY, RT
AF ABRAMSON, MA
   DIETZE, R
   FRUCHT, DM
   SCHWANTZ, R
   KENNEY, RT
TI COMPARISON OF NEW AND OLD-WORLD LEISHMANINS IN AN ENDEMIC REGION OF
   BRAZIL
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID AMERICAN CUTANEOUS LEISHMANIASIS; MONTENEGRO SKIN-TEST; VISCERAL
   LEISHMANIASIS; KALA-AZAR; MEDITERRANEAN LEISHMANIASIS; IMMUNE-RESPONSE;
   EPIDEMIOLOGY; INFECTION; ANTIGENS; COLOMBIA
AB The control of leishmaniasis depends on a knowledge of the magnitude of the disease and of exposure to it, Delayed-type hypersensitivity testing can detect prior exposure to the parasite, but there is little agreement regarding the choice of an antigen for such testing, New and Old World leishmanins were tested in a study of patients with confirmed prior cutaneous leishmaniasis (CL), patients with confirmed prior American visceral leishmaniasis (AVL), and controls from areas in Espirito Santo, Brazil, where leishmaniasis is not endemic, Biobras antigen (a suspended mixture of Leishmania braziliensis guyanensis, Leishmania mexicana amazonensis, and Leishmania mexicana promastigotes) detected 100% of prior CL infections and thus was superior to the Old World antigen, Leishmania major, which detected only 19% of these infections (P <.00001), Soluble New World antigens of Leishmania chagasi evoked a response in 96% of cases of prior AVL, whereas the Old World counterpart, Leishmania infantum, evoked a response in 71% of cases (P <.042), Testing of family members of patients with prior AVL showed greater utility of the New World leishmanins and suggested subclinical exposure of a large number of healthy people in the hyperendemic region, New World skin-test antigens should be used in future epidemiological studies in the Americas to more accurately determine the extent of exposure.
C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892.
   UNIV FED ESPIRITO SANTO,VITORIA,BRAZIL.
   DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710.
NR 51
TC 13
Z9 14
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY
PY 1995
VL 20
IS 5
BP 1292
EP 1297
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA QY771
UT WOS:A1995QY77100032
PM 7620013
ER

PT J
AU EISENHOFER, G
   FRIBERG, P
   PACAK, K
   GOLDSTEIN, DS
   MURPHY, DL
   TSIGOS, C
   QUYYUMI, AA
   BRUNNER, HG
   LENDERS, JWM
AF EISENHOFER, G
   FRIBERG, P
   PACAK, K
   GOLDSTEIN, DS
   MURPHY, DL
   TSIGOS, C
   QUYYUMI, AA
   BRUNNER, HG
   LENDERS, JWM
TI PLASMA METADRENALINES - DO THEY PROVIDE USEFUL INFORMATION ABOUT
   SYMPATHOADRENAL FUNCTION AND CATECHOLAMINE METABOLISM
SO CLINICAL SCIENCE
LA English
DT Article
DE ADRENAL GLANDS; ADRENALECTOMY; ADRENALINE; CATECHOL-O-METHYLTRANSFERASE;
   DIHYDROXYPHENYLGLYCOL; HEART FAILURE; HYPERTENSION; METADRENALINE;
   MONOAMINE OXIDASE; NORADRENALINE; NORMETADRENALINE; NORRIE DISEASE;
   PHEOCHROMOCYTOMA; SYMPATHETIC NERVOUS SYSTEM
ID MONOAMINE-OXIDASE; CONJUGATED NORMETANEPHRINE; ELECTROCHEMICAL
   DETECTION; LIQUID-CHROMATOGRAPHY; HYPERTENSIVE PATIENTS; GENE;
   NOREPINEPHRINE; DELETION; EPINEPHRINE; TONE
AB 1. The clinical utility of plasma metadrenalines for examination of sympatho-adrenal function and catecholamine metabolism was assessed from plasma measurements of these metabolites in a number of clinical conditions (hypertension, cardiac failure, bilateral adrenalectomy and X-chromosomal deletions of the gene for monoamine oxidase), and before and during activation of sympathetic outflow or infusions of noradrenaline and adrenaline.
   2. Plasma concentrations of normetadrenaline were less than 25% of those of noradrenaline, concentrations of metadrenaline and adrenaline were similar and those of sulphate-conjugated metadrenalines were 20- to 30-fold higher than free metradrenalines. Hypertensive patients had elevated plasma concentrations of adrenaline, noradrenaline and conjugated but not free metradrenalines. Cardiac failure patients had 2- to 4-fold increases in plasma noradrenaline and free and conjugated normetadrenaline. Adrenalectomy resulted in undetectable plasma concentrations of adrenaline, 91-97% decreases in free and conjugated metadrenaline and a 40% decrease in normetadrenaline relative to noradrenaline. Patients with X-chromosomal deletions of the gene for monoamine oxidase had 6- and 16-fold increases in plasma free and conjugated normetadrenaline and 2- and 4-fold increases in free and conjugated metadrenaline.
   3. Infusion of catecholamines increased plasma concentrations of free metadrenalines by less than 6% of increases in precursor amines, indicating that most plasma normetadrenaline (84%) and metadrenaline (90%) is derived from metabolism of catecholamines before their entry into the circulation. Considerable O-methylation of catecholamines within the adrenals explains why sympatho-adrenal activation resulted in smaller proportional increases in plasma metadrenalines than catecholamines.
   4. Plasma metadrenalines provide supplementary information about sympatho-adrenal activity to that provided by catecholamines, but are more useful for examination of the extraneuronal inactivation of catecholamines, particularly detection of neurochemical phenotypes in genetic disorders of catecholamine metabolism. Significant formation of metadrenalines within chromaffin tissue explains why measurements of plasma metadrenalines provide an extraordinarily sensitive method for diagnosis of phaeochromocytoma.
C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892.
   NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892.
   NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892.
   UNIV GOTEBORG,DEPT CLIN PHYSIOL,GOTHENBURG,SWEDEN.
   ST RADBOUD HOSP,DEPT INTERNAL MED,NIJMEGEN,NETHERLANDS.
RP EISENHOFER, G (reprint author), NINCDS,CLIN NEUROSCI BRANCH,ROOM 5N214,BLDG 10,10 CTR DR MSC 1424,BETHESDA,MD 20892, USA.
RI Brunner, Han/C-9928-2013; Lenders, J.W.M./L-4487-2015
NR 35
TC 78
Z9 79
U1 1
U2 2
PU PORTLAND PRESS
PI LONDON
PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ
SN 0143-5221
J9 CLIN SCI
JI Clin. Sci.
PD MAY
PY 1995
VL 88
IS 5
BP 533
EP 542
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA RA290
UT WOS:A1995RA29000005
PM 7614812
ER

PT J
AU HISSA, R
   JOHN, MT
   PILO, B
   VISWANATHAN, M
   GEORGE, JC
AF HISSA, R
   JOHN, MT
   PILO, B
   VISWANATHAN, M
   GEORGE, JC
TI NORADRENALINE-INDUCED HYPOTHERMIA IS SUPPRESSED IN THE VAGOTOMIZED
   COLD-EXPOSED PIGEON
SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY
LA English
DT Article
DE BILATERAL VAGOTOMY; HYPOTHERMIA; NORADRENALINE; PIGEON
ID ADRENAL-GLAND; CARDIORESPIRATORY RESPONSES; SHIVERING THERMOGENESIS;
   INHIBITORY INNERVATION; CIRCULATING LEVELS; VAGAL INNERVATION; HYPOXIA;
   CATECHOLAMINES
AB Vagotomized (VX) pigeons studied 2 days after surgery exhibited a significant decrease in cloacal temperature (T-b) and respiratory rate (R(f)), and an increase in heart rate (H-f) and metabolic rate (M) at the thermoneutral zone, when compared with sham-operated (SVX) pigeons. The effect of intravenous noradrenaline (NA) on T-b, R(f), H-f and M was examined in SVX and VX-pigeons at 15 degrees C. Following NA administration, the T-b and R(f) in the SVX-birds dropped from the preinjection level, but in VX-pigeons, they were not significantly altered. In SVX-pigeons, a total suppression of shivering was apparent following NA-injection, while in the majority of VX-pigeons, shivering was only slightly affected or even increased. The H-f in both SVX- and VX-birds increased following NA-injection. The responses to reserpine were qualitatively similar to NA, although much slower. There were no differences between SVX- and VX-birds with regard to T-b, M and R(f) following acetylcholine (ACh) and eserine (Ese) injection, H-f increased after ACh + Ese administration in SVX-pigeons, but in VX-birds, it decreased after an initial surge. Shivering was suppressed for 18-20 min in SVX-birds and 30-50 min in VX-birds. It is suggested that the lack of the hypothermic effect of NA in VX-birds is due to the maintenance of oxygen uptake with unimpaired capacity for shivering.
C1 UNIV GUELPH,DEPT ZOOL,GUELPH,ON N1G 2W1,CANADA.
   UNIV GUELPH,DEPT ZOOL,GUELPH,ON N1G 2W1,CANADA.
   NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892.
RP HISSA, R (reprint author), UNIV OULU,DEPT ZOOL,SF-90570 OULU,FINLAND.
NR 40
TC 3
Z9 3
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0300-9629
J9 COMP BIOCHEM PHYS A
JI Comp. Biochem. Physiol. A-Physiol.
PD MAY
PY 1995
VL 111
IS 1
BP 89
EP 97
DI 10.1016/0300-9629(95)98524-K
PG 9
WC Biochemistry & Molecular Biology; Physiology; Zoology
SC Biochemistry & Molecular Biology; Physiology; Zoology
GA QW035
UT WOS:A1995QW03500010
PM 7735913
ER

PT J
AU WOLFFE, AP
AF WOLFFE, AP
TI CENTROMERIC CHROMATIN - HISTONE DEVIANTS
SO CURRENT BIOLOGY
LA English
DT Note
ID PROTEIN CENP-A; SATELLITE DNA; NUCLEOSOME
AB Highly variant histones are targeted to specialized chromatin domains, such as the centromere where they have an essential role in the segregation of sister chromatids mitosis.
RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA.
NR 14
TC 16
Z9 17
U1 0
U2 0
PU CURRENT BIOLOGY LTD
PI LONDON
PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD MAY 1
PY 1995
VL 5
IS 5
BP 452
EP 454
DI 10.1016/S0960-9822(95)00088-1
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QX049
UT WOS:A1995QX04900002
PM 7583085
ER

PT J
AU ROTH, DB
   LINDAHL, T
   GELLERT, M
AF ROTH, DB
   LINDAHL, T
   GELLERT, M
TI REPAIR AND RECOMBINATION - HOW TO MAKE ENDS MEET
SO CURRENT BIOLOGY
LA English
DT Note
ID STRAND BREAK-REPAIR; V(D)J RECOMBINATION; SCID MUTATION; DNA;
   DEFICIENCY; MUTANTS
AB The repair of double-stranded breaks in DNA and the recombination of antibody gene V(D)J segments share a common pathway involving the Ku protein, which binds DNA ends, and its associated protein kinase.
C1 IMPERIAL CANC RES FUND,CLARE HALL LABS,S MIMMS EN6 3LD,HERTS,ENGLAND.
   NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892.
RP ROTH, DB (reprint author), BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030, USA.
NR 25
TC 109
Z9 109
U1 0
U2 1
PU CURRENT BIOLOGY LTD
PI LONDON
PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD MAY 1
PY 1995
VL 5
IS 5
BP 496
EP 499
DI 10.1016/S0960-9822(95)00101-1
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QX049
UT WOS:A1995QX04900015
PM 7583098
ER

PT J
AU KREITMAN, RJ
   PURI, RK
   MCPHIE, P
   PASTAN, I
AF KREITMAN, RJ
   PURI, RK
   MCPHIE, P
   PASTAN, I
TI CIRCULARLY PERMUTED INTERLEUKIN-4 RETAINS PROLIFERATIVE AND
   BINDING-ACTIVITY
SO CYTOKINE
LA English
DT Article
DE CYTOKINE; GROWTH FACTOR; MUTEIN
ID MAGNETIC-RESONANCE SPECTROSCOPY; 3-DIMENSIONAL SOLUTION STRUCTURE;
   RECOMBINANT HUMAN INTERLEUKIN-4; RECEPTOR GAMMA-CHAIN; SECONDARY
   STRUCTURE; CARCINOMA-CELLS; EXPRESSION; PROTEINS; VARIANTS; LYMPHOCYTES
AB In human interleukin 4(IL-4), the carboxyl and amino termini of the 129 amino acid hormone are close to each other and this region is believed to be important for binding to the IL-4 receptor (IL-4r). We constructed plasmids encoding circularly permuted IL-4 mutants with the peptide Gly-Gly-Asn-Gly-Gly (GGNGG) joining the carboxyl to the amino terminus and with new amino and carboxyl termini elsewhere. Mutant IL-4(38-37) is composed of IL-4 residues 38-129, GGNGG and 1-37. Mutant IL-4(105-104) is composed of IL-4 residues 105-129, GGNGG and 1-104. IL-4(38-37) and IL-4(105-104) were purified from E. coli to near homogeneity and retained 50-100% of the binding and proliferative activity of IL-4, and in addition retained the ability to upregulate CD23 on Burkitt's lymphoma cells. Circular dichroism studies indicated that the tertiary structures of both IL-4(38-37) and IL-4(105-104) were retained, with the former molecule most similar to native IL-4. We conclude that while both native termini of IL-4 may be near its binding site, neither is required to be free for optimum activity.
C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892.
   NIH,US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892.
   NIDDKD,DIV INTRAMURAL RES,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892.
NR 44
TC 17
Z9 17
U1 0
U2 1
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD MAY
PY 1995
VL 7
IS 4
BP 311
EP 318
DI 10.1006/cyto.1995.0039
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA RB161
UT WOS:A1995RB16100002
PM 8589260
ER

PT J
AU CHREST, FJ
   BUCHHOLZ, MA
   KIM, YH
   KWON, TK
   NORDIN, AA
AF CHREST, FJ
   BUCHHOLZ, MA
   KIM, YH
   KWON, TK
   NORDIN, AA
TI ANTI-CD3-INDUCED APOPTOSIS IN T-CELLS FROM YOUNG AND OLD MICE
SO CYTOMETRY
LA English
DT Article
DE APOPTOSIS; AGING; T-CELL ACTIVATION; T-CELL SUBSETS; MEMORY T-CELLS;
   FLOW CYTOMETRY
ID DNA STRAND BREAKS; FLOW-CYTOMETRY; LYMPHOCYTES-T; MURINE THYMOCYTES;
   CD4+8+ THYMOCYTES; ELDERLY HUMANS; AGED MICE; ACTIVATION; EXPRESSION;
   RECEPTOR
AB Light scatter measurements using now cytometry indicated that T cells from young and old mice undergo apoptosis following activation with immobilized anti-CD3. The percentage of cells in apoptosis after 20 h activation was significantly greater (p < .001) in cultures containing cells from older animals, The mean percentages of apoptotic T cells from young and old mice after 20 h activation were 19.3% and 33.0%, respectively. The proportion of viable cells after 20 h activation was significantly higher (p <.003) in the young (mean = 78.4%) than in the old animals (mean = 65.8%), Simultaneous measurements of Light scatter and fluorescence indicated that apoptotic T cells contained both the CD4(+) and the CD8(+) T-cell phenotypes. The frequency of apoptotic CD8(+) T cells was elevated (p <.007) in older animals, where the mean percentage was 15.1%, compared to 5.3% in the young. The most dramatic difference between young and old (P <.0008) was seen in the percentages of viable CD4(+) T cells after 20 h activation. The mean viable CD4(+) T-cell percentage was 33.7% in the young and 21.4% in the old, CD4(+) cells expressing high levels of CD45RB (CD45RB(hi)) after activation for 20 h possessed light scatter and bright fluorescence properties characteristic of viable cells, whereas CD4(+)/CD45RB(lo) density cells could be identified as apoptotic based on their decreased CD4 fluorescence and scatter characteristics. CD4(+) cells from young animals were predominantly CD45RB(hi), whereas CD4(+) cells from the old had greater levels of CD454RB(lo) cells.
   In addition to light scatter changes, measurement of DNA content after 40 h activation revealed the presence of a sub-G, DNA apoptotic peak and a viable cell cycle distribution. After 40 h of activation, there was an increase in the percentage of apoptotic cells in both young and old mice, with the greatest increase seen in the cells from older animals. Further evidence supporting the process of apoptosis in 40 h-activated cells was confirmed by the appearance of DNA strand breaks detected by in situ nick translation. (C) 1995 Wiley-Liss, Inc.
RP CHREST, FJ (reprint author), NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA.
NR 38
TC 41
Z9 41
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 0196-4763
J9 CYTOMETRY
JI Cytometry
PD MAY 1
PY 1995
VL 20
IS 1
BP 33
EP 42
DI 10.1002/cyto.990200107
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QV464
UT WOS:A1995QV46400006
PM 7600898
ER

PT J
AU WERSTO, RP
   STETLERSTEVENSON, M
AF WERSTO, RP
   STETLERSTEVENSON, M
TI DEBRIS COMPENSATION OF DNA HISTOGRAMS AND ITS EFFECT ON S-PHASE ANALYSIS
SO CYTOMETRY
LA English
DT Article
DE S-PHASE; DEBRIS SUBTRACTION; DNA HISTOGRAM
ID NEGATIVE BREAST-CANCER; PARAFFIN-EMBEDDED BREAST; FLOW CYTOMETRIC
   ANALYSIS; SOLID TUMORS; FRACTION; VARIABILITY; CARCINOMAS;
   DISTRIBUTIONS; SURVIVAL; SAMPLES
AB Debris compensation is an important variable affecting S-phase fraction (SPF) analysis in now cytometric DNA histograms. The SPF was estimated in fresh frozen breast carcinomas using the following four debris subtraction algorithms: modeling debris as an exponential curve (EXP); the incorporation of nuclei cut a single time into the exponential moel (EXP-SC); the random cutting of nuclei into multiple pieces of varying sizes (MC); and a combination of both nuclear cutting models (SC-MG). Comparison of SPF estimates indicated that the various debris subtraction models yielded differences in SPF, with SPF values obtained using the exponential model having considerable variation compared to SPF estimates from histograms where debris was modeled by algorithms based on nuclear slicing and fragmentation. However, SPF estimates could be affected by initial placement of the nuclear debris boundaries, the coefficient of variation of the G(0/1) peak, and the relative amount of debris. Using the ratio of the height of the G(0/1) peak to the height of the debris between the chicken red blood cells (CRBC) and G(0/1) peaks as an objective measurement of nuclear debris, debris compensation was necessary in diploid DNA histograms where this ratio was as low as 1.5%. Taken in the context of SPF prognostic cutoff levels, variation in debris models and boundaries can change the classification of cases with borderline SPF levels into the poor prognostic high SPF categories, thereby making the comparison of SPF values derived from different studies difficult. (C) 1995 Wiley-Liss, Inc.
C1 NCI,PATHOL LAB,BETHESDA,MD 20892.
NR 44
TC 20
Z9 20
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012
SN 0196-4763
J9 CYTOMETRY
JI Cytometry
PD MAY 1
PY 1995
VL 20
IS 1
BP 43
EP 52
DI 10.1002/cyto.990200108
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA QV464
UT WOS:A1995QV46400007
PM 7600899
ER

PT J
AU GAO, CY
   BASSNETT, S
   ZELENKA, PS
AF GAO, CY
   BASSNETT, S
   ZELENKA, PS
TI CYCLIC-B, P34(CDC2), AND H1-KINASE ACTIVITY IN TERMINALLY
   DIFFERENTIATING LENS FIBER CELLS
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID POLYMERASE CHAIN-REACTION; EMBRYONIC CHICKEN LENS; PROTEIN-KINASE; CDC2
   KINASE; TYROSINE PHOSPHORYLATION; MESSENGER-RNA; M-PHASE; EXPRESSION;
   DNA; IDENTIFICATION
AB Terminal differentiation of lens fiber cells is marked by chromatin condensation, abrupt dissolution of the nuclear lamina, vesicularization of the nuclear membrane, and complete degradation of the nucleus and other organelles. Since these events resemble the chromosomal condensation and nuclear envelope breakdown associated with mitosis, we investigated whether a similar biochemical mechanism might be involved by testing for the presence of cyclin B/p34(cdc2) complexes and p34(cdc2)-associated histone kinase activity in differentiating lens fiber cells. A coupled reverse transcription/polymerase chain reaction using RNA from E7, E15, or E20 embryonic chicken lens fibers amplified a cyclin B product of the expected size, whose identity was confirmed by sequencing. In situ hybridization showed that cyclin B mRNA was present in nucleated lens fiber cells at E19. Immunoblotting of proteins isolated from E6 or E15 lens fibers by p13-agarose affinity chromatography with anti-cyclin B antibody detected the 45-kDa cyclin B protein, while immunoblotting with anti-PSTAIRE antibody detected a single, 34-kDa band, identified as p34(cdc2). Th, p13-affinity purified fraction from E6 or E15 lens fibers showed histone H1 kinase activity in vitro. Immunocytochemistry of E6 lenses with anti-chicken cyclin B antiserum showed positive staining in the nuclei of postmitotic annular pad and fiber cells. These results demonstrate that cyclinB/p34(cdc2) complexes and p34(cdc2)-associated histone kinase activity are present in postmitotic, differentiating lens fiber cells and support the possibility that phosphorylation of specific nuclear substrates by p34(cdc2) may play a role in the denucleation of lens fiber cells. (C) 1995 Academic Press, Inc.
C1 UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814.
RP GAO, CY (reprint author), NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA.
FU NEI NIH HHS [EY09852]
NR 54
TC 31
Z9 35
U1 0
U2 0
PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
PI SAN DIEGO
PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAY
PY 1995
VL 169
IS 1
BP 185
EP 194
DI 10.1006/dbio.1995.1136
PG 10
WC Developmental Biology
SC Developmental Biology
GA QY794
UT WOS:A1995QY79400016
PM 7750637
ER

PT J
AU ZAHNWAXLER, C
AF ZAHNWAXLER, C
TI PARENTAL DEPRESSION AND DISTRESS - IMPLICATIONS FOR DEVELOPMENT IN
   INFANCY, CHILDHOOD, AND ADOLESCENCE - INTRODUCTION TO SPECIAL SECTION
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Editorial Material
RP ZAHNWAXLER, C (reprint author), NIMH,DEV PSYCHOL LAB,BLDG 15-K,BETHESDA,MD 20892, USA.
NR 0
TC 14
Z9 14
U1 0
U2 1
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 1995
VL 31
IS 3
BP 347
EP 348
PG 2
WC Psychology, Developmental
SC Psychology
GA QX191
UT WOS:A1995QX19100001
ER

PT J
AU TARULLO, LB
   DEMULDER, EK
   RONSAVILLE, DS
   BROWN, E
   RADKEYARROW, M
AF TARULLO, LB
   DEMULDER, EK
   RONSAVILLE, DS
   BROWN, E
   RADKEYARROW, M
TI MATERNAL DEPRESSION AND MATERNAL TREATMENT OF SIBLINGS AS PREDICTORS OF
   CHILD PSYCHOPATHOLOGY
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
ID PARENTAL DEPRESSION; FAMILY; RELIABILITY; PERCEPTIONS; ADJUSTMENT;
   MOTHERS; RISK
AB Maternal treatment of sibling pairs with affectively ill and well mothers was examined longitudinally in relation to child psychiatric status. Mothers and children in 77 families (34 unipolar, 16 bipolar, and 27 control mothers) were observed in interaction across early, middle, and late childhood and early adolescence. Interaction was assessed on dimensions of maternal engagement and critical-irritable behavior. The study examined the relative contributions of maternal depression, the quality of maternal treatment, and differential treatment of siblings to each child's psychiatric status. By maternal report, older siblings' symptoms were predicted by maternal bipolar or unipolar illness; younger siblings' symptoms were predicted by lower maternal engagement and higher maternal critical-irritable behavior in early childhood, in addition to maternal affective illness. For the younger sibling, persistent patterns of maternal treatment were also related to both maternal and child reports of problems.
RP TARULLO, LB (reprint author), NIMH,BLDG 15-K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA.
NR 43
TC 22
Z9 22
U1 3
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 1995
VL 31
IS 3
BP 395
EP 405
DI 10.1037/0012-1649.31.3.395
PG 11
WC Psychology, Developmental
SC Psychology
GA QX191
UT WOS:A1995QX19100007
ER

PT J
AU KNOWLER, WC
   NARAYAN, KMV
   HANSON, RL
   NELSON, RG
   BENNETT, PH
   TUOMILEHTO, J
   SCHERSTEN, B
   PETTITT, DJ
AF KNOWLER, WC
   NARAYAN, KMV
   HANSON, RL
   NELSON, RG
   BENNETT, PH
   TUOMILEHTO, J
   SCHERSTEN, B
   PETTITT, DJ
TI PREVENTING NON-INSULIN-DEPENDENT DIABETES
SO DIABETES
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; TERM WEIGHT CONTROL; 10-YEAR FOLLOW-UP;
   PIMA-INDIANS; RISK-FACTORS; MELLITUS; DIET; DISEASE; TYPE-2;
   CLASSIFICATION
AB Many risk factors for non-insulin-dependent diabetes mellitus (NIDDM), such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Furthermore, some of the metabolic abnormalities, such as insulin resistance and impaired glucose tolerance, that predict diabetes can be improved by behavior modification and drug treatment. Thus, at feast to some extent, NIDDM may be preventable. Several small clinical trials have addressed the hypothesis that NIDDM can be prevented by dietary modification, physical activity, or drug treatments. Some studies suggest a preventive effect, but the conclusions are limited by considerations of sample size, randomization, or intensity of the interventions. Consequently, the hypothesis that NIDDM is preventable requires further testing.
C1 NIDDKD,PHOENIX,AZ 85016.
   NATL INST PUBL HLTH,HELSINKI,FINLAND.
   LUND UNIV,LUND,SWEDEN.
RI Nelson, Robert/B-1470-2012; Narayan, K.M. Venkat /J-9819-2012; Hanson,
   Robert/O-3238-2015
OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson,
   Robert/0000-0002-4252-7068
NR 57
TC 106
Z9 108
U1 1
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1660 DUKE ST, ALEXANDRIA, VA 22314
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAY
PY 1995
VL 44
IS 5
BP 483
EP 488
DI 10.2337/diabetes.44.5.483
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QZ820
UT WOS:A1995QZ82000001
PM 7729603
ER

PT J
AU LEE, ET
   HOWARD, BV
   SAVAGE, PJ
   COWAN, LD
   FABSITZ, RR
   OOPIK, AJ
   YEH, JL
   GO, O
   ROBBINS, DC
   WELTY, TK
AF LEE, ET
   HOWARD, BV
   SAVAGE, PJ
   COWAN, LD
   FABSITZ, RR
   OOPIK, AJ
   YEH, JL
   GO, O
   ROBBINS, DC
   WELTY, TK
TI DIABETES AND IMPAIRED GLUCOSE-TOLERANCE IN 3 AMERICAN-INDIAN POPULATIONS
   AGED 45-74 YEARS - THE STRONG HEART-STUDY
SO DIABETES CARE
LA English
DT Article
ID PIMA-INDIANS; MELLITUS; PREVALENCE; COMMUNITY; MORTALITY; HEALTH;
   TRIBES; DEATH
AB OBJECTIVE- To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors. age, obesity, family history of diabetes, and amount of Indian ancestry.
   RESEARCH DESIGN AND METHODS- This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio.
   RESULTS- A total of 4,549 eligible participants were examined, and diabetes status was determined for 4,304 (1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status.
   CONCLUSIONS- Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs should be expanded to include those with IGT to improve glycemic control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.
C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT BIOSTAT & EPIDEMIOL,OKLAHOMA CITY,OK 73190.
   MEDLANT RES INST,WASHINGTON,DC.
   NHLBI,BETHESDA,MD 20892.
   ABERDEEN AREA INDIAN HLTH SERV,AURORA,CO.
   ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD.
   FITZSIMONS ARMY MED CTR,AURORA,CO 80045.
RP LEE, ET (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,COLL PUBL HLTH,CTR EPIDEMIOL RES,POB 26901,OKLAHOMA CITY,OK 73190, USA.
FU NHLBI NIH HHS [UO1 HL-41654, UO1 HL-41642, UO1 HL-41652]
NR 34
TC 127
Z9 128
U1 1
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1660 DUKE ST, ALEXANDRIA, VA 22314
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAY
PY 1995
VL 18
IS 5
BP 599
EP 610
DI 10.2337/diacare.18.5.599
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QW299
UT WOS:A1995QW29900001
PM 8585996
ER

PT J
AU CHEW, EY
   MILLS, JL
   METZGER, BE
   REMALEY, NA
   JOVANOVICPETERSON, L
   KNOPP, RH
   CONLEY, M
   RAND, L
   SIMPSON, JL
   HOLMES, LB
   AARONS, JH
AF CHEW, EY
   MILLS, JL
   METZGER, BE
   REMALEY, NA
   JOVANOVICPETERSON, L
   KNOPP, RH
   CONLEY, M
   RAND, L
   SIMPSON, JL
   HOLMES, LB
   AARONS, JH
TI METABOLIC CONTROL AND PROGRESSION OF RETINOPATHY - THE DIABETES IN
   EARLY-PREGNANCY STUDY
SO DIABETES CARE
LA English
DT Article
ID INFANTS; MOTHERS; MALFORMATIONS; HEMOGLOBIN; MELLITUS; OSLO
AB OBJECTIVE- To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy.
   RESEARCH DESIGN AND METHODS- We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the Ist trimester and monthly thereafter.
   RESULTS- In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin greater than or equal to 6 SD above the control mean Versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039).
   CONCLUSIONS- The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy, Excellent metabolic control before conception may be required to avoid this increase in risk, Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.
C1 NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892.
   NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611.
   SANSUM MED RES FDN,SANTA BARBARA,CA 93105.
   UNIV WASHINGTON,NW LIPID RES CLIN,SEATTLE,WA.
   MED EYE ASSOCIATES,NORWOOD,MA.
   BAYLOR COLL MED,HOUSTON,TX 77030.
   BRIGHAM & WOMENS HOSP,BOSTON,MA 02115.
   MAGEE WOMENS HOSP,PITTSBURGH,PA 15213.
RP CHEW, EY (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA.
FU Intramural NIH HHS [Z99 EY999999]; NCRR NIH HHS [RR-00037-28, RR-48];
   PHS HHS [R0047]
NR 26
TC 141
Z9 143
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1660 DUKE ST, ALEXANDRIA, VA 22314
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAY
PY 1995
VL 18
IS 5
BP 631
EP 637
DI 10.2337/diacare.18.5.631
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QW299
UT WOS:A1995QW29900005
PM 8586000
ER

PT J
AU UDALOVA, IA
   TURETSKAYA, RL
   KUPRASH, DV
   NEDOSPASOV, SA
AF UDALOVA, IA
   TURETSKAYA, RL
   KUPRASH, DV
   NEDOSPASOV, SA
TI 2 LEVELS OF TRANSCRIPTIONAL ACTIVATION OF HUMAN TNF GENE IN MACROPHAGES
   - ROLE OF NF-KAPPA-B/REL PROTEINS IN LPS INDUCTION
SO DOKLADY AKADEMII NAUK
LA Russian
DT Article
ID NECROSIS-FACTOR-ALPHA; HUMAN-MONOCYTES; LIPOPOLYSACCHARIDE; EXPRESSION;
   ENHANCERS; PROMOTER; CELLS
C1 NCI,FREDERICK,MD 21701.
RP UDALOVA, IA (reprint author), VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA.
RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash,
   Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016
OI Kuprash, Dmitry/0000-0002-1488-4148; 
NR 15
TC 5
Z9 5
U1 0
U2 0
PU MEZHDUNARODNAYA KNIGA
PI MOSCOW
PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA
SN 0869-5652
J9 DOKL AKAD NAUK+
JI Dokl. Akad. Nauk
PD MAY
PY 1995
VL 342
IS 3
BP 413
EP 417
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA RJ281
UT WOS:A1995RJ28100033
PM 7655369
ER

PT J
AU DOMANSKI, MJ
   COLLERAN, JA
   CUNNION, RE
   NANDA, NC
AF DOMANSKI, MJ
   COLLERAN, JA
   CUNNION, RE
   NANDA, NC
TI CORRELATION OF ECHOCARDIOGRAPHIC FRACTIONAL AREA CHANGE WITH
   RADIONUCLIDE LEFT-VENTRICULAR EJECTION FRACTION
SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED
   TECHNIQUES
LA English
DT Article
DE CARDIAC IMAGING; ECHOCARDIOGRAPHY; SYSTOLIC FUNCTION; RADIONUCLIDE
   VENTRICULOGRAPHY
AB Fractional area change of the left ventricle during systole, measured in the parasternal short-axis view, is an easily calculated index of systolic function. We assessed the correlation of echocardiographic left ventricular fractional area change with radionuclide ventriculography derived Left ventricular ejection fraction. Forty patients who had both echocardiography and radionuclide ventriculography were studied. Nonuniformity of left ventricular function was present in 38%. For the group as a whole the correlation. coefficient for fractional area change and ejection fraction was 0.82 (P < 0.001). For patients with uniform systolic function the correlation coefficient was 0.79 (P < 0.001). For those with regional differences, the correlation coefficient was 0.72 (P < 0.005). We conclude that echocardiographically derived fractional area change, measured in the parasternal short-axis view, is an excellent measure of left ventricular function even in patients with heterogeneity of regional function.
RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BLDG 10,BETHESDA,MD 20892, USA.
NR 0
TC 3
Z9 4
U1 0
U2 0
PU FUTURA PUBL CO
PI ARMONK
PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418
SN 0742-2822
J9 ECHOCARDIOGR-J CARD
JI Echocardiogr.-J. Cardiovasc. Ultrasound Allied Techn.
PD MAY
PY 1995
VL 12
IS 3
BP 221
EP 227
DI 10.1111/j.1540-8175.1995.tb00542.x
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA QW997
UT WOS:A1995QW99700001
ER

PT J
AU CHRAMBACH, A
   YARMOLA, E
   ZAKHAROV, SF
   GARNER, MM
AF CHRAMBACH, A
   YARMOLA, E
   ZAKHAROV, SF
   GARNER, MM
TI COMMERCIAL AUTOMATED GEL-ELECTROPHORESIS APPARATUS - APPLICATION TO DNA,
   BAND DISPERSION, NONLINEAR FERGUSON CURVES, AND ISOLATION
SO ELECTROPHORESIS
LA English
DT Article; Proceedings Paper
CT International Meeting on Electrophoresis Forum 94
CY OCT 24-26, 1994
CL MUNICH, GERMANY
SP German Electrophoresis Sco
DE GEL ELECTROPHORESIS; AUTOMATION; DISPERSION; PREPARATIVENESS
ID POLYMER MEDIA; BUFFER SYSTEM; MOBILITY DATA; AGAROSE; POLYACRYLAMIDE;
   GRADIENT; PROTEINS
AB Recently available commercial automated gel electrophoresis apparatus with intermittent scanning of fluorescently labeled gel patterns (the HPGE-1000 apparatus of LabIntelligence, Menlo Park CA) was tested with regard to (i) its applicability to DNA in its native conformation, (ii) its ability to recognize the correct number of components, (iii) its capability to evaluate the width and shape of bands detected during electrophoresis, (iv) its ability to yield nonlinear Ferguson plots in a labor-saving fashion, and (v) its preparative potential. Ethidium homodimer (EtD) DNA (bp) ratios were systematically varied and the mobility of DNA fragments labeled at each ratio was measured in order to find a ratio which provided an unaltered mobility and presumably therefore an unaltered conformation of the fragment. That ratio was found to be 1/40 EtD/DNA (bp) or less. With such weak labeling of DNA, a representative fragment of 527 bp length requires a minimum load of 200 ng and a 2 mu g load for a full-scale peak height. Using the baseline automatically selected by the software of the apparatus, the band areas of the 17 components of a DNA digest were consistently evaluated by the software, as evidenced by the proportionality between DNA length and area. The areas of the separated bands of DNA fragments of 1857 and 121 bp length were found to be constant with time of electrophoresis. The dispersion coefficient was found to decrease with agarose concentration in electrophoresis at 1 V/cm; however, at higher field strength, the band width of the 1857 bp fragment was surprisingly found to increase with gel concentration, presumably due to stretching. Electrophoretic band dispersion was not found to be due to diffusion since zone spreading in the absence of the electric field under otherwise identical conditions does not proceed measurably: For the discontinuous buffer system of Wiltfang et al. (Electrophoresis 1993, 12, 352-366) the resolving power, in terms of theoretical plate equivalents, was approximately threefold higher compared to that in the Tris-borate-EDTA (TEE) buffer under otherwise identical conditions. Two electrophoretic runs of the apparatus with different gel concentrations in its eight channels suffice to define nonlinear Ferguson curves, provided that the free mobility is measured by capillary electrophoresis. The commercial automated apparatus excels as a preparative device by allowing one to monitor the qualitative and quantitative success of electroelution.
RP CHRAMBACH, A (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C215,BETHESDA,MD 20892, USA.
NR 26
TC 4
Z9 4
U1 1
U2 2
PU VCH PUBLISHERS INC
PI DEERFIELD BEACH
PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788
SN 0173-0835
J9 ELECTROPHORESIS
JI Electrophoresis
PD MAY
PY 1995
VL 16
IS 5
BP 713
EP 718
DI 10.1002/elps.11501601115
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA RE073
UT WOS:A1995RE07300006
PM 7588549
ER

PT J
AU YANOVSKI, JA
AF YANOVSKI, JA
TI THE DEXAMETHASONE-SUPPRESSED CORTICOTROPIN-RELEASING HORMONE TEST IN THE
   DIFFERENTIAL-DIAGNOSIS OF HYPERCORTISOLISM
SO ENDOCRINOLOGIST
LA English
DT Article
ID PITUITARY-ADRENAL-FUNCTION; CUSHINGS-SYNDROME; STIMULATION TEST;
   CORTISOL; DISEASE; ADRENOCORTICOTROPIN; METABOLISM; SECRETION;
   DEPRESSION; LOPERAMIDE
AB It is often difficult to distinguish patients with mild Cushing's syndrome from obese patients with pseudo-Cushing states who also have increased cortisol production. Several tests are described as useful in determining which patients have Cushing's syndrome, but none have high sensitivity and specificity for the diagnosis of Cushing's syndrome. This paper reviews a new test developed at the NIH, the dexamethasone-suppressed CRH test, which appears to be quite useful in making the difficult discrimination between mild Cushing's disease and pseudo-Cushing states. A single cortisol value measured after 2 days of low-dose dexamethasone suppression and 15 minutes after CRH stimulation was 100% specific and sensitive for the diagnosis of Cushing's syndrome. Limitations of the test, and suggestions for its interpretation, are discussed.
RP YANOVSKI, JA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA.
OI Yanovski, Jack/0000-0001-8542-1637
NR 46
TC 5
Z9 5
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 1051-2144
J9 ENDOCRINOLOGIST
JI Endocrinologist
PD MAY
PY 1995
VL 5
IS 3
BP 169
EP 175
DI 10.1097/00019616-199505000-00003
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QZ179
UT WOS:A1995QZ17900003
ER

PT J
AU LANDAU, D
   CHIN, E
   BONDY, C
   DOMENE, H
   ROBERTS, CT
   GRONBAEK, H
   FLYVBJERG, A
   LEROITH, D
AF LANDAU, D
   CHIN, E
   BONDY, C
   DOMENE, H
   ROBERTS, CT
   GRONBAEK, H
   FLYVBJERG, A
   LEROITH, D
TI EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN THE
   RAT-KIDNEY - EFFECTS OF LONG-TERM DIABETES
SO ENDOCRINOLOGY
LA English
DT Article
ID RECEPTOR GENE-EXPRESSION; FACTOR-I; RENAL HYPERTROPHY; IGF-I;
   GLOMERULAR-FILTRATION; ALBUMIN EXCRETION; MESSENGER-RNA; SECRETION;
   HORMONE; SIZE
AB Recent studies have shown that the renal synthesis of insulin-like growth factor binding proteins (IGFBPs) is altered in insulin-deficient diabetes mellitus, suggesting that these changes may be implicated in the alterations in renal function and morphology that accompany diabetes. To investigate the time course and the precise cellular distribution of changes in IGFBP expression, we used quantitative in situ hybridization to analyze renal IGF-I and IGFBP-1 to -5 messenger RNA (mRNA)localization and levels from 2 days to 6 months after the onset of streptozotocin-induced diabetes. There was an immediate sharp decline in IGF-I mRNA levels in the outer medulla that persisted for up to 3 months and a much smaller reduction in IGF-I mRNA levels in the medullary thick ascending limbs (MTALs). In nondiabetic animals, IGFBP-1 mRNA is most abundant in the MTALs. Immediately after the induction of diabetes, however, there was a greater than a-fold increase in cortical IGFBP-1 mRNA and a 75% decrease in IGFBP-1 mRNA in MTALs. These changes persisted for up to 6 months in the diabetic animals. In contrast, IGFBP-5 mRNA levels were increased in the outer medulla and decreased in the cortex of diabetic kidneys. No significant changes in renal IGFBP-2 mRNA level or distribution were noted, and changes in IGFBP-3 and -4 mRNA levels were subtle. In summary, streptozotocin-induced diabetes is associated with very prominent and complex alterations in renal IGF system gene expression, including robust increases in cortical IGFBP-1 and profound decreases in cortical IGFBP-5 mRNA and medullary IGF-I mRNA levels. The divergent changes in IGFBP-1 and -5 mRNA levels in cortex vs. outer medulla indicate that regulation of IGFBP mRNA levels is quite complex.
C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892.
   NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892.
   AARHUS KOMMUNE HOSP,INST EXPTL CLIN RES,DK-8000 AARHUS C,DENMARK.
   CHILDRENS HOSP NATL CTR,DEPT NEPHROL,WASHINGTON,DC 20010.
OI Gronbaek, Henning/0000-0001-8998-7910; Roberts,
   Charles/0000-0003-1756-5772
NR 40
TC 76
Z9 77
U1 0
U2 0
PU ENDOCRINE SOC
PI BETHESDA
PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 1995
VL 136
IS 5
BP 1835
EP 1842
DI 10.1210/en.136.5.1835
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QU628
UT WOS:A1995QU62800004
PM 7536658
ER

PT J
AU SRIVASTAVA, RK
   GU, Y
   ZILBERSTEIN, M
   OU, JS
   MAYO, KE
   CHOU, JY
   GIBORI, G
AF SRIVASTAVA, RK
   GU, Y
   ZILBERSTEIN, M
   OU, JS
   MAYO, KE
   CHOU, JY
   GIBORI, G
TI DEVELOPMENT AND CHARACTERIZATION OF A SIMIAN-VIRUS 40-TRANSFORMED,
   TEMPERATURE-SENSITIVE RAT ANTIMESOMETRIAL DECIDUAL CELL-LINE
SO ENDOCRINOLOGY
LA English
DT Article
ID MESSENGER-RIBONUCLEIC-ACID; PSEUDOPREGNANT RAT; GRANULOSA-CELLS;
   BINDING-PROTEIN; BETA-SUBUNIT; ACTIVIN; INHIBIN; ESTABLISHMENT;
   FOLLISTATIN; LUTEOTROPIN
AB The rat decidual tissue is formed by two cell populations, which express different genes and play diverse roles in pregnancy. Cells that decidualize in the antimesometrial region secrete several hormones and serve as a true endocrine gland. Isolation and maintenance of these decidual cells in primary culture is difficult. The goal of these experiments was to develop a cell line to serve as a model to study the expression and regulation of various genes specific to the antimesometrial decidual cells. Decidualization was induced in pseudopregnant rats. The antimesometrial decidua was dissected out, and cells were enzymatically dissociated and were cultured for 18 h at 37 C in RPMI-1640 medium containing 10% fetal bovine serum. Cells were washed repeatedly and then infected with a temperature-sensitive mutant of the simian virus. Transformed cells were maintained at the permissive temperature (33 C) until colonies were identified and harvested. Whereas primary cells in culture did not divide, the cloned decidual cell lines demonstrated transformed features; they multiplied at 33 C and formed multilayers. At the nonpermissive temperature (39 C), cell replication decreased, and after 4 days of culture the cells lost their transformed phenotype and continued to grow as a monolayer similar to primary cells. Cells under these conditions also assumed morphological characteristics similar to antimesometrial cells: polynucleated, large, and having cytoplasm filled with lipid droplets. Interestingly, cells cultured at 39 C that were shifted back to 33 C resumed rapid growth. To determine whether these cells also express messenger RNAs (mRNAs) found in normal antimesometrial decidual cells, the presence of activin beta(A) mRNA was investigated by Northern analysis and reverse transcription polymerase chain reaction. A single 6.8-kilobase activin beta(A) transcript was expressed abundantly at both 33 and 39 C, indicating that even when cells are rapidly dividing they express activin beta(A). Activin beta(B) mRNA was also expressed in these cells, although in lower abundance, as were two binding proteins for activin, activin receptor II and follistatin. The activin beta(A) and beta(B) genes were responsive to cAMP stimulation in these cells. Since the hallmark of the antimesometrial decidual cells is the secretion of PRL-related hormones, the expression of decidual PRL-related protein and PRL-like protein B was examined. Northern analysis revealed a major 1.2-kilobase transcript of PRL-Like protein B expressed equally at both temperatures. However, decidual PRL-related protein mRNA was not detected in this cell Line, and expression of this gene was not induced with progesterone treatment, despite the fact that these cells express the progesterone receptor mRNA at the nonpermissive temperature.
   In summary, a temperature-sensitive cell-line was successfully established from the endocrine cells of the rat decidua, and these cells express many of the genes encoding hormones and receptors inherent to this defined decidual cell population.
C1 UNIV ILLINOIS, DEPT PHYSIOL & BIOPHYS, CHICAGO, IL 60612 USA.
   NORTHWESTERN UNIV, DEPT BIOCHEM MOLEC BIOL & CELL BIOL, EVANSTON, IL 60208 USA.
   NICHHD, HUMAN GENET BRANCH, BETHESDA, MD 20892 USA.
FU NHLBI NIH HHS [T32 HL-07692]; NICHD NIH HHS [HD-12356, HD-27491]
NR 37
TC 22
Z9 22
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 1995
VL 136
IS 5
BP 1913
EP 1919
DI 10.1210/en.136.5.1913
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QU628
UT WOS:A1995QU62800015
PM 7720638
ER

PT J
AU LIPOSITS, Z
   REID, JJ
   NEGROVILAR, A
   MERCHENTHALER, I
AF LIPOSITS, Z
   REID, JJ
   NEGROVILAR, A
   MERCHENTHALER, I
TI SEXUAL DIMORPHISM IN COPACKAGING OF LUTEINIZING-HORMONE-RELEASING
   HORMONE AND GALANIN INTO NEUROSECRETORY VESICLES OF HYPOPHYSIOTROPHIC
   NEURONS - ESTROGEN DEPENDENCY
SO ENDOCRINOLOGY
LA English
DT Article
ID RAT ANTERIOR-PITUITARY; LH-RH NEURONS; MEDIAN-EMINENCE; HYPOTHALAMIC
   NEURONS; INSITU HYBRIDIZATION; PREOPTIC AREA; GENE-EXPRESSION;
   LOCALIZATION; BRAIN; VASOPRESSIN
AB Hypophysiotrophic neurons projecting to hypophyseal portal vessels in the median eminence of the hypothalamus maintain the operation of the master gland, the pituitary, by secreting releasing and release-inhibiting hormones into the bloodstream. LHRH, synthesized in neurons of the rat prosencephalon, is one of the key substances that governs the anterior pituitary-gonadal axis. Recently, it has been shown that the peptide galanin (GAL) is coproduced in a subpopulation of LHRH neurons and is a potent modulator of central processes regulating reproduction. A better understanding of the secretory mechanisms involved in pulsatile hormone release from LHRH axons of the median eminence requires exploration of the organelle domain that displays the cosynthesized peptides in terminal boutons. This study shows that LHRH- and GAL-immunoreactive axons overlap heavily in the lateral part of the median eminence. Double fluorescent labeling revealed colocalization of the peptides at the level of single axon terminals. By means of dual colloidal gold immunolabeling, LHRH and GAL were detected in the same secretory vesicles at the ultrastructural level. The incidence of colocalizing vesicles was high in the female (45%) and low in the male (3%) rat. Ovariectomy resulted in a dramatic decline in the number of LHRH/GAL-coexpressing vesicles (23%), which was reversed (55%) by the administration of estradiol. The observations indicate a sex-related difference in the packaging of LHRH and GAL and suggest that the events are estrogen dependent. Furthermore, the simultaneous release of GAL and LHRH from the colocalizing vesicles provides a mechanism that might ensure the potentiating effect of GAL on LHRH by synchronizing events at the receptor sites in the anterior pituitary.
C1 NIEHS,FUNCT MORPHOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709.
   NIEHS,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709.
NR 49
TC 39
Z9 41
U1 0
U2 2
PU ENDOCRINE SOC
PI BETHESDA
PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 1995
VL 136
IS 5
BP 1987
EP 1992
DI 10.1210/en.136.5.1987
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QU628
UT WOS:A1995QU62800025
PM 7536660
ER

PT J
AU FABBRI, A
   CIOCCA, DR
   CIAMPANI, T
   WANG, J
   DUFAU, ML
AF FABBRI, A
   CIOCCA, DR
   CIAMPANI, T
   WANG, J
   DUFAU, ML
TI GROWTH HORMONE-RELEASING HORMONE IN TESTICULAR INTERSTITIAL AND
   GERM-CELLS - POTENTIAL PARACRINE MODULATION OF
   FOLLICLE-STIMULATING-HORMONE ACTION ON SERTOLI-CELL FUNCTION
SO ENDOCRINOLOGY
LA English
DT Article
ID RAT LEYDIG-CELLS; INTERMEDIATE ROLE; CYCLIC-AMP; LOCALIZATION;
   GONADOTROPIN; CULTURES; PROTEIN; TESTIS
AB GH-releasing hormone (GHRH) is present in the interstitial and germ cells of the rat testis. In previous studies we found that GHRH is secreted from rat adult Leydig cells, in which it stimulates basal and LH-induced cAMP formation and steroidogenesis. In other studies cAMP production in Sertoli cells was found to be stimulated by GHRH. In the present report, we describe a potential paracrine action of GHRH in the Sertoli cell, with stimulation of cAMP formation in cultured adult and pubertal Sertoli cells. GHRH increased FSH-stimulated cAMP production in adult and pubertal cultures in a time-dependent manner. GHRH stimulation of basal and FSH-induced extracellular cAMP formation was more prominent in pubertal than in adult cultures. Immunocytochemical studies demonstrated the presence of GHRH-like immunoreactivity in rat interstitial cells from day 4 to adult life and in the acrosomal region of early and intermediate spermatids at stages III-VI of the seminiferous epithelium cycle. Immunoreactive GHRH was not observed in late spermatids and mature sperm or in Sertoli cells at any age. These results indicate that GHRH acts synergistically with FSH to promote cAMP production in Sertoli cells in culture. Testicular GHRH of Leydig and germ cell origin may be an important paracrine regulator of Sertoli cell function. Alternatively, GHRH present in germ cells may exert stage-specific intracrine functions.
C1 NICHHD,ENDOCRINOL REPROD RES BRANCH,BETHESDA,MD 20892.
   NICHHD,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892.
   LAB REPROD & LACTANCIA,MENDOZA,ARGENTINA.
NR 26
TC 21
Z9 21
U1 0
U2 0
PU ENDOCRINE SOC
PI BETHESDA
PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 1995
VL 136
IS 5
BP 2303
EP 2308
DI 10.1210/en.136.5.2303
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QU628
UT WOS:A1995QU62800066
PM 7720679
ER

PT J
AU GRAY, K
   EITZMAN, B
   RASZMANN, K
   STEED, T
   GEBOFF, A
   MCLACHLAN, J
   BIDWELL, M
AF GRAY, K
   EITZMAN, B
   RASZMANN, K
   STEED, T
   GEBOFF, A
   MCLACHLAN, J
   BIDWELL, M
TI COORDINATE REGULATION BY DIETHYLSTILBESTROL OF THE PLATELET-DERIVED
   GROWTH FACTOR-A (PDGF-A) AND FACTOR-B CHAINS AND THE PDGF RECEPTOR
   ALPHA-SUBUNIT AND BETA-SUBUNIT IN THE MOUSE UTERUS AND VAGINA -
   POTENTIAL MEDIATORS OF ESTROGEN ACTION
SO ENDOCRINOLOGY
LA English
DT Article
ID MESSENGER RIBONUCLEIC-ACID; SMOOTH-MUSCLE CELLS; RAT UTERUS;
   GENE-EXPRESSION; INSULIN-LIKE; TGF-BETA; DEVELOPMENTAL EXPRESSION;
   REPRODUCTIVE-TRACT; PORCINE UTERUS; FACTOR-I
AB The effects of estrogen on the reproductive tract involve cell proliferation, migration, and differentiation, which need to be well coordinated. Polypeptide growth factors are believed to play a vital role in a number of these cellular processes. Among the growth factors now documented to be associated with estrogen action are epidermal growth factor, transforming growth factor-alpha (TGF alpha), transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and insulin-like growth factor-I (IGF-I). Platelet-derived growth factors (PDGFs) are also potent mitogens, which consist of two peptide chains, denoted A and B, that dimerize to isoforms (PDGF-AA, -AB, and -BB) which differ in their functional properties, secretory behavior, receptor binding, and physiological effects. To study the role of the PDGF-A and -B chains and the PDGF receptor subunits, alpha and beta, during estrogen action in the mouse reproductive tract, time-dependent changes in the expression of these genes were examined by Northern and in situ RNA. analyses and by immunohistochemistry after a single treatment of immature CD-1 (17- to 19-day-old) mice with the synthetic estrogen, diethylstilbestrol (DES). Our results demonstrate estrogen modulation of the expression of messenger RNA (mRNA) and protein for the PDGF ligands and receptors in both the uterus and vagina of the mouse. Northern and in situ RNA analyses demonstrate time-dependent estrogen induction of the mRNA levels for these genes in both tissues within 3 h after treatment. However, distinctive mRNA expression profiles for the PDGF ligand and receptor genes are exhibited by the uterus and vagina in response to DES, especially in that the induction of transcripts for PDGF-A and both receptor subunits is more transient in the vagina than in the uterus. Steroid specificity studies demonstrate predominant estrogen-specific regulation of mRNA induction for these genes. Analysis of cell-specific RNA expression by in situ hybridization reveals prominent induction of transcripts for the PDGF chains and receptor subunits in the uterine and vaginal epithelium after estrogen treatment, although enhanced expression of mRNA is also noted in the stroma, particularly for the PDGF receptor subunit genes. Cellular localization of the PDGF ligand and receptor protein molecules by immunohistochemistry detected significant immunostaining for all of these proteins in both the uterus and vagina of control animals. After DES treatment, the uterus exhibits a significant decrease in the level of PDGF ligand and receptor proteins immunostained within 6 h, whereas less dramatic effects are observed in the vagina. Affinity labeling of PDGF alpha-receptor with [I-125]PDGF-AA establishes the presence of functional PDGF ct-receptor in the uterus and vagina. Estrogen treatment is found to reduce the amount of PDGF alpha-receptor that can be covalently labeled in both tissues, especially in the uterus. This reduction in affinity labeling of the PDGF receptor is in agreement with the finding of decreased immunostaining for the PDGF receptors in these tissues and supports estrogen modulation of PDGF receptors in the reproductive tract. The induction of the PDGF ligand and receptor genes by estrogen is a relatively early event, occurring many hours before the initiation of DNA synthesis in the uterine and vaginal epithelium, which implicates the PDGF signal transduction pathway in estrogen-mediated growth.
   Based on the coexpression of the potent PDGF mitogens and their receptors in the mouse reproductive tract, our findings demonstrate the presence in vivo of another powerful autocrine or paracrine loop that is regulated by estrogen, which probably plays an important role in estrogen action by coordinating growth and differentiation. Collectively, these data and other in vivo studies have now shown that estrogen regulates multiple peptide growth factors in the reproductive tract, which suggest that estrogen stimulation of DNA synthesis may be controlled by potent competence (PDGF and PDGF receptors) and progression (TGF alpha, epidermal growth factor, IGF-I, IGF-II, and their receptors) factors interacting by autocrine/paracrine mechanisms to insure a synchronized integrated tissue growth response.
C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709.
NR 73
TC 43
Z9 43
U1 0
U2 0
PU ENDOCRINE SOC
PI BETHESDA
PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 1995
VL 136
IS 5
BP 2325
EP 2340
DI 10.1210/en.136.5.2325
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA QU628
UT WOS:A1995QU62800070
PM 7720681
ER

PT J
AU RHODES, N
   PAULES, RS
   ROBERTS, JD
AF RHODES, N
   PAULES, RS
   ROBERTS, JD
TI MOLECULAR MECHANISMS OF ENVIRONMENTAL CARCINOGENESIS
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 NIEHS,ENVIRONM CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709.
   NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU NATL INST ENVIRON HEALTH SCI
PI RES TRIANGLE PK
PA PO BOX 12233, RES TRIANGLE PK, NC 27709
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 1995
VL 103
IS 5
BP 504
EP 506
DI 10.2307/3432590
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA RW440
UT WOS:A1995RW44000025
PM 7656881
ER

PT J
AU BARRON, MG
   ALBRO, PW
   HAYTON, WL
AF BARRON, MG
   ALBRO, PW
   HAYTON, WL
TI BIOTRANSFORMATION OF DI(2-ETHYLHEXYL)PHTHALATE BY RAINBOW-TROUT
SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
LA English
DT Note
DE PHTHALATE; TROUT; BIOTRANSFORMATION; P450; GLUCURONIDATION
ID DI-2-ETHYLHEXYL PHTHALATE; TEMPERATURE-DEPENDENCE; SALMO-GAIRDNERI;
   METABOLISM; PHARMACOKINETICS; FISH
AB The biotransformation of di (2-ethylhexyl)phthalate (DEHP) was studied in rainbow trout (Oncorhynchus mykiss) following intravascular administration. Methyl-esterified metabolites were identified using rodent-derived standards and nonlinear gradient elution HPLC; metabolites were confirmed by gas chromatography. Similarities between the biotransformation of DEHP by rainbow trout and mammalian species included (a) mono-ethylhexyl phthalate (MEHP) appeared to be the obligatory first step in DEHP metabolism; (b) the phthalate ring was not oxidized; (c) phthalic acid was a minor metabolite; and (d) several metabolites contained multiple oxidations of the 2-ethylhexyl moiety of MEHP. No metabolites unique to rainbow trout were identified. However, fewer oxidized metabolites were identified in rainbow trout than in mammalian species, possibly due to limited mitochondrial metabolism of MEHP in rainbow trout. The amount of biliary MEHP glucuronide after intravascular administration of DEHP was substantially less than reported in rainbow trout exposed to DEHP via the water. Results confirmed that DEHP metabolism in rainbow trout proceeds by initial rapid formation of MEHP, followed by excretion or extensive oxidation by microsomal P450.
C1 NIEHS,RES TRIANGLE PK,NC 27709.
   OHIO STATE UNIV,COLL PHARM,COLUMBUS,OH 43210.
RP BARRON, MG (reprint author), HAGLER BAILLY INC,RCG,PO DRAWER O,BOULDER,CO 80306, USA.
NR 21
TC 20
Z9 21
U1 7
U2 19
PU SETAC PRESS
PI PENSACOLA
PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370
SN 0730-7268
J9 ENVIRON TOXICOL CHEM
JI Environ. Toxicol. Chem.
PD MAY
PY 1995
VL 14
IS 5
BP 873
EP 876
DI 10.1897/1552-8618(1995)14[873:BODBRT]2.0.CO;2
PG 4
WC Environmental Sciences; Toxicology
SC Environmental Sciences & Ecology; Toxicology
GA QV456
UT WOS:A1995QV45600019
ER

PT J
AU STURGEON, SR
   SCHAIRER, C
   BRINTON, LA
   PEARSON, T
   HOOVER, RN
AF STURGEON, SR
   SCHAIRER, C
   BRINTON, LA
   PEARSON, T
   HOOVER, RN
TI EVIDENCE OF A HEALTHY ESTROGEN USER SURVIVOR EFFECT
SO EPIDEMIOLOGY
LA English
DT Article
DE MENOPAUSAL ESTROGENS; MORTALITY; SELECTION BIAS; COHORT STUDY
AB We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study. We found a lower all-cause mortality rate among women who took estrogens [rate ratio (RR) = 0.7; 95% confidence interval (CI) = 0.7-0.8], particularly current users (RR = 0.3; 95% CI = 0.2-0.4), than among women who never took them. Additional analyses, however, revealed that women who had recently stopped taking estrogens had a higher all-cause mortality rate than women who had never taken them (RR = 1.4; 95% CI = 1.2-1.7). Women who had recently stopped taking estrogens also had higher mortality rates from circulatory disease (RR = 1.3; 95% CI = 1.0-1.8) and cancer (RR = 1.6; 95% CI = 1.2-2.2) than women who never took them. The most likely explanation for these results is that women stop taking estrogens when they develop symptoms of serious illness. As a consequence of this ''healthy estrogen user survivor effect,'' nonexperimental studies are susceptible to overestimating the benefits of menopausal estrogen use, particularly current use, on mortality.
RP STURGEON, SR (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,6130 EXECUT BLVD,ROOM 443,BETHESDA,MD 20892, USA.
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
NR 0
TC 121
Z9 123
U1 0
U2 5
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 1995
VL 6
IS 3
BP 227
EP 231
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QU354
UT WOS:A1995QU35400006
PM 7619927
ER

PT J
AU WEINBERG, CR
AF WEINBERG, CR
TI SHOULD WE ADJUST FOR PREGNANCY HISTORY WHEN THE EXPOSURE EFFECT IS
   TRANSIENT
SO EPIDEMIOLOGY
LA English
DT Letter
RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA.
NR 0
TC 7
Z9 7
U1 0
U2 1
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 1995
VL 6
IS 3
BP 335
EP 336
DI 10.1097/00001648-199505000-00028
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QU354
UT WOS:A1995QU35400028
PM 7619949
ER

PT J
AU WEINBERG, CR
AF WEINBERG, CR
TI SHOULD WE ADJUST FOR PREGNANCY HISTORY WHEN THE EXPOSURE EFFECT IS
   TRANSIENT - RESPONSE
SO EPIDEMIOLOGY
LA English
DT Letter
RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILLIAMS & WILKINS
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 1995
VL 6
IS 3
BP 337
EP 337
DI 10.1097/00001648-199505000-00030
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA QU354
UT WOS:A1995QU35400030
ER

PT J
AU HERMANN, BP
   GOLD, J
   PUSAKULICH, R
   WYLER, AR
   RANDOLPH, C
   RANKIN, G
   HOY, W
AF HERMANN, BP
   GOLD, J
   PUSAKULICH, R
   WYLER, AR
   RANDOLPH, C
   RANKIN, G
   HOY, W
TI WECHSLER ADULT INTELLIGENCE SCALE-REVISED IN THE EVALUATION OF ANTERIOR
   TEMPORAL LOBECTOMY CANDIDATES
SO EPILEPSIA
LA English
DT Article
DE EPILEPSY SURGERY; ANTERIOR TEMPORAL LOBECTOMY; NEUROPSYCHOLOGY; WAIS-R;
   INTELLIGENCE
ID COGNITIVE-INTELLECTUAL PERFORMANCE; MAJOR MOTOR EPILEPSY;
   NEUROPSYCHOLOGICAL PERFORMANCE; SEIZURE FREQUENCY; LATE ONSET; CHILDREN
AB We wished to (a) determine the ability of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to discriminate between patients with epilepsy of left or right temporal lobe (LTLE, RTLE) origin and (b) examine the ability of Kaufman's (1990) WAIS-R short forms to estimate actual Full-Scale IQ (FSIQ). We administered the WAIS-R to 215 nonretarded, left hemisphere dominant patients with invasively verified epilepsy of unilateral TL origin without lesions demonstrated by magnetic resonance imaging (MRI) (excluding mesial temporal sclerosis, MTS). LTLE (n = 106) and RTLE (n = 109) groups were compared on the WAIS-R subtests and summary IQ scores, Verbal-Performance IQ (VIQ-PIQ) discrepancies of various magnitudes, and Verbal Comprehension (VC) and Perceptual Organization (PO) scores derived by factor analysis. The LTLE group scored significantly lower on the Vocabulary subtest, and none of the other indexes reliably distinguished LTLE from RTLE patients. The Kaufman 2, 3, and 4 subtest short forms were significant predictors of FSIQ, with the 4 subtest short form having the highest correlation and lowest error of estimate.
C1 UNIV TENNESSEE,BAPTIST MEM HOSP,CTR EPI CARE,MEMPHIS,TN.
   UNIV TENNESSEE,DEPT PSYCHIAT,MEMPHIS,TN.
   UNIV TENNESSEE,DEPT NEUROSURG,MEMPHIS,TN.
   VET ADM MED CTR,MEMPHIS,TN 38104.
   NIMH,WASHINGTON,DC.
   SWEDISH MED CTR,CTR EPILEPSY,SEATTLE,WA.
NR 50
TC 26
Z9 26
U1 1
U2 2
PU LIPPINCOTT-RAVEN PUBL
PI PHILADELPHIA
PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD MAY
PY 1995
VL 36
IS 5
BP 480
EP 487
DI 10.1111/j.1528-1157.1995.tb00490.x
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA QU939
UT WOS:A1995QU93900009
PM 7614926
ER

PT J
AU SHRAGER, RI
   HENDLER, RW
   BOSE, S
AF SHRAGER, RI
   HENDLER, RW
   BOSE, S
TI THE ABILITY OF ACTINIC LIGHT TO MODIFY THE BACTERIORHODOPSIN PHOTOCYCLE
   - HETEROGENEITY AND/OR PHOTOCOOPERATIVITY
SO EUROPEAN JOURNAL OF BIOCHEMISTRY
LA English
DT Review
DE BACTERIORHODOPSIN; LIGHT INTENSITY; PHOTOCYCLE REGULATION; MATHEMATICAL
   MODELS; KINETICS; M-INTERMEDIATES
ID PURPLE MEMBRANE; HALOBACTERIUM-HALOBIUM; PARALLEL PHOTOCYCLES; RESONANCE
   RAMAN; PROTEIN; FORMS; PH
AB The focus of this paper is on the established observation that the bacteriorhodopsin (BR) photocycle responds to the level of actinic light by altering the proportions of two forms of the M intermediate. The first form of M, called M-fast or M(F), decays to the O intermediate. In contrast, the second form of M, called M-slow or M(S), decays directly to the ground state, and its decay rate is slower than that of M(F). Any proposed scheme for the BR photocycle must account for this light-dependent phenomenon. Several papers have attempted to explain the observation on the basis of photocooperativity, or on the basis of heterogeneous populations. In this paper, we test previously proposed cooperative models with experimental data, and find those models to be inadequate. We show that two new models, one purely cooperative, the other purely heterogeneous, can both fit the data, hence such modelling will not resolve the mechanism. Taking into account the demonstration of heterogeneity, the trimer structure of BR, and certain experimental evidence in favor of cooperativity, it appears likely that both heterogeneity and cooperativity are involved in the adaptation of the BR photocycle to different levels of actinic light.
C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892.
   NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892.
NR 22
TC 27
Z9 27
U1 0
U2 2
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 MAY 1
PY 1995
VL 229
IS 3
BP 589
EP 595
DI 10.1111/j.1432-1033.1995.tb20502.x
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA QW630
UT WOS:A1995QW63000001
PM 7758451
ER

PT J
AU EMMONS, KM
   THOMPSON, B
   FENG, Z
   HEBERT, JR
   HEIMENDINGER, J
   LINNAN, L
AF EMMONS, KM
   THOMPSON, B
   FENG, Z
   HEBERT, JR
   HEIMENDINGER, J
   LINNAN, L
TI DIETARY-INTAKE AND EXPOSURE TO ENVIRONMENTAL TOBACCO-SMOKE IN A WORKSITE
   POPULATION
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE DIET; ENVIRONMENTAL TOBACCO SMOKE; NUTRITION WORKSITES
ID LUNG-CANCER; ALPHA-TOCOPHEROL; PASSIVE SMOKING; BETA-CAROTENE;
   VITAMIN-A; RISK; NONSMOKERS
AB Objectives: Nonsmokers who live with smokers have poorer dietary habits than those who live in nonsmoking households. This relationship may be due to shared lifestyle patterns by spouses and family members. However, in order to fully understand the nature of this relationship, it is also important to examine the association between diet and exposure to environmental tobacco smoke (ETS) at the workplace. Further, blue collar workers' patterns of exposure to ETS both at work and at home have not been studied. The goal of this study is to examine the dietary intake of manufacturing workers as it relates to exposure to ETS at work and at home.
   Methods: The Working Well Trial surveyed 10 833 nonsmokers about a variety of health behaviors, including smoking, dietary behaviors, and ETS exposure.
   Results. Nonsmokers who had ETS exposure in their household had significantly lower intake of all target micronutrients, compared to those without household exposure. Exposure to ETS at the workplace was associated with lower intakes of vitamin C and fruits and vegetables, but not the other micronutrients examined.
   Conclusions: Exposure to ETS was associated with poorer dietary habits. Household exposure was a stronger predictor of intake than was workplace exposure. Because of the antagonistic effects of many components of a healthful diet in relation to the harmful effects of tobacco smoke, these findings have relevance larger than either ETS exposure or diet considered singly.
C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98101.
   UNIV MASSACHUSETTS,SCH MED,WORCESTER,MA 01655.
   NCI,ROCKVILLE,MD 20852.
   MIRIAM HOSP,PROVIDENCE,RI 02906.
RP EMMONS, KM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV COMMUNITY BASED RES,44 BINNEY ST,BOSTON,MA 02115, USA.
FU NCI NIH HHS [U01CA51686, U01CA5A51671, U01 CA51687]
NR 38
TC 24
Z9 26
U1 1
U2 2
PU STOCKTON PRESS
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
SN 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD MAY
PY 1995
VL 49
IS 5
BP 336
EP 345
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA QY954
UT WOS:A1995QY95400004
PM 7664719
ER

PT J
AU OFFENHAUSER, N
   BOHMMATTHAEI, R
   TSOULFAS, P
   PARADA, L
   MEYER, M
AF OFFENHAUSER, N
   BOHMMATTHAEI, R
   TSOULFAS, P
   PARADA, L
   MEYER, M
TI DEVELOPMENTAL REGULATION OF FULL-LENGTH TRKC IN THE RAT SCIATIC-NERVE
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE NEUROTROPHIN; SCHWANN CELL; TRKB; TRUNCATED RECEPTOR; TYROSINE KINASE
ID GROWTH-FACTOR RECEPTOR; DORSAL-ROOT GANGLIA; NEURAL CREST CELLS;
   NEUROTROPHIC FACTOR; TYROSINE KINASE; MESSENGER-RNA; SENSORY NEURONS;
   FACTOR FAMILY; DIFFERENTIAL RESPONSE; MOLECULAR-CLONING
AB In order to gain insight into potential roles of neurotrophins in Schwann cell biology, the expression of neurotrophin receptors of the trk gene family was investigated in rat sciatic nerve development, This analysis revealed differential regulation of truncated and full-length receptors, TrkA was undetectable even when analysed with a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method. TrkB was present at the mRNA as well as protein level only in its truncated form. Surprisingly, multiple isoforms of trkC, including full-length forms, were detected in early postnatal nerve. Specific antibodies detected truncated and full-length trkC proteins in Western blotting, and RT-PCR revealed the presence of two full-length isoforms, one of them containing the 14 amino acid kinase insert. In situ hybridisation localized the expression of trkC to a subpopulation of Schwann cells. TrkC receptors are expressed already in nerves from day-16 embryos. In contrast to early postnatal stages, full-length trkC receptors are no longer expressed in adult nerves, which, however, maintain expression of truncated trkC transcripts. The presence of trkC kinases in peripheral nerve suggests a role for neurotrophin-3, the only known trkC ligand, in peripheral nerve development.
C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD.
   UNIV TEXAS,SW MED CTR,CTR DEV BIOL,DALLAS,TX 75235.
RP OFFENHAUSER, N (reprint author), MAX PLANCK INST PSYCHIAT,KLOPFERSPITZ 18A,D-82152 MARTINSRIED,GERMANY.
OI Offenhauser, Nina/0000-0002-3316-3047; Tsoulfas,
   Pantelis/0000-0003-1974-6366
NR 55
TC 43
Z9 43
U1 0
U2 0
PU OXFORD UNIV PRESS UNITED KINGDOM
PI OXFORD
PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAY 1
PY 1995
VL 7
IS 5
BP 917
EP 925
DI 10.1111/j.1460-9568.1995.tb01079.x
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA QY001
UT WOS:A1995QY00100010
PM 7613627
ER

PT J
AU SURMACZ, E
   SELL, C
   SWANTEK, J
   KATO, H
   ROBERTS, CT
   LEROITH, D
   BASERGA, R
AF SURMACZ, E
   SELL, C
   SWANTEK, J
   KATO, H
   ROBERTS, CT
   LEROITH, D
   BASERGA, R
TI DISSOCIATION OF MITOGENESIS AND TRANSFORMING ACTIVITY BY C-TERMINAL
   TRUNCATION OF THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
ID TYROSINE KINASE-ACTIVITY; SIGNAL TRANSDUCTION; DOMAIN;
   AUTOPHOSPHORYLATION; SH2; EXPRESSION; RESISTANCE; SEQUENCE; ANTIGEN;
   LACKING
AB We have investigated the mitogenic and transforming ability of an IGF-I receptor with a 108-amino-acid C-terminal truncation in R(-) cells, which are 3T3-like cells derived from mouse embryos in which the IGF-I receptor genes have been disrupted by targeted homologous recombination, R(-) cells stably transfected with expression plasmids encoding either a wild-type or a truncated human IGF-I receptor were capable of growing in serum-free medium supplemented solely with IGF-I, This response was observed over a wide range of receptor levels, R(-) cells overexpressing the wild-type IGF-I receptor also formed colonies in soft agar, and colony formation was augmented by coexpression of the SV40 large T antigen, However, all the examined clones of R(-) cells expressing the truncated IGF-I receptor exhibited a dramatically impaired ability to grow in soft agar, even in the presence of the T antigen, The inability to form colonies in soft agar was not due to a quantitative impairment of signal transduction, because: (1) SV40-transformed cells with a physiological level of the wild-type IGF-I receptor did not respond to IGF-I with cell proliferation, but grew in soft agar; (2) R(-) cells stably transfected with both a truncated receptor and T antigen, on the contrary, responded with mitogenesis to IGF-I but could not form colonies in soft agar; (3) some clones with the truncated receptor expressed levels of receptor roughly 100-fold the level of wild-type cells; and (4) several parameters of IGF-I receptor signal transduction were not impaired in cells stably transfected with a truncated receptor, Furthermore, overexpression of an activated ras in cells with the truncated IGF-IR did not restore their ability to proliferate under anchorage-independent conditions. We conclude that the last 108 amino acids of the IGF-I receptor are not essential for a mitogenic response to IGF-I, but are required for transformation (as assessed by the ability to grow in soft agar), indicating that these two functions can be dissociated at an intramolecular level. Moreover, although ras (activated) certainly plays a role in transformation, the transforming activity of the IGF-IR also requires signaling elements that are ras-independent. (C) 1995 Academic Press, Inc.
C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892.
RP SURMACZ, E (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,BLSB 624,233 S 10TH ST,PHILADELPHIA,PA 19107, USA.
OI Roberts, Charles/0000-0003-1756-5772
FU NCI NIH HHS [CA 53484, 5-T32-CA09678]; NIGMS NIH HHS [GM 33694]
NR 46
TC 73
Z9 73
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 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD MAY
PY 1995
VL 218
IS 1
BP 370
EP 380
DI 10.1006/excr.1995.1168
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA QW998
UT WOS:A1995QW99800045
PM 7737373
ER

PT J
AU ROTH, GS
AF ROTH, GS
TI CHANGES IN TISSUE RESPONSIVENESS TO HORMONES AND NEUROTRANSMITTERS
   DURING AGING
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article; Proceedings Paper
CT Symposium on the Neurobiology and Neuroendocrinology of Aging
CY JUL 24-28, 1994
CL BREGENZ, AUSTRIA
SP SO ILLINOIS UNIV CARBONDALE, PRESIDENTS OFF, SO ILLINOIS UNIV CARBONDALE, GRAD SCH, SO ILLINOIS UNIV SCH MED, SPRINGFIELD, ILLINOIS, USA & LAND VORARLBERG, AUSTRIA
DE AGING; HORMONES; NEUROTRANSMITTERS; TISSUE RESPONSE
ID MESSENGER-RNA; EGF RECEPTOR; RAT; STRIATUM; RECOVERY; BLOCKADE; PROTEIN;
   NEURONS
AB Responsiveness to many hormones and neurotransmitters by target tissues is altered during aging. Three model systems that are representative of these changes are reviewed. These are (1) striatal dopaminergic regulation of motor function, (2) IP3 and calcium-mediated electrolyte and neurosecretion by the alpha(1)-adrenergic and muscarinic cholinergic systems in parotid and corpus striatum, and (3) beta adrenergic and epidermal growth factor (EGF) stimulated DNA synthesis in hepatocytes.
RP ROTH, GS (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,BALTIMORE,MD 21224, USA.
NR 30
TC 34
Z9 35
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB
SN 0531-5565
J9 EXP GERONTOL
JI Exp. Gerontol.
PD MAY-AUG
PY 1995
VL 30
IS 3-4
BP 361
EP 368
DI 10.1016/0531-5565(94)00029-3
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA RA381
UT WOS:A1995RA38100014
PM 7556514
ER

PT J
AU SOMA, T
   DUNBAR, CE
AF SOMA, T
   DUNBAR, CE
TI IN-VIVO MODELS FOR STUDYING THE ROLE OF AUTOCRINE OR PARACRINE
   GROWTH-FACTORS IN HEMATOLOGIC MALIGNANCIES
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Review
ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; ACUTE
   MYELOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; TRANSGENIC MICE;
   CASTLEMANS DISEASE; MULTIPLE-MYELOMA; GENE-TRANSFER; INTERLEUKIN-6;
   EXPRESSION
C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892.
NR 50
TC 6
Z9 6
U1 0
U2 0
PU CARDEN JENNINGS PUBL COLTD
PI CHARLOTTESVILLE
PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD MAY
PY 1995
VL 23
IS 5
BP 385
EP 388
PG 4
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA QW623
UT WOS:A1995QW62300001
PM 7720810
ER

PT J
AU EBERHARD, ML
   DICKERSON, JW
   TSANG, VCW
   WALKER, EM
   OTTESEN, EA
   CHANDRASHEKAR, R
   WEIL, GJ
   TRPIS, M
   STROBERT, E
   CONSTANTINIDIS, I
   SWENSON, RB
AF EBERHARD, ML
   DICKERSON, JW
   TSANG, VCW
   WALKER, EM
   OTTESEN, EA
   CHANDRASHEKAR, R
   WEIL, GJ
   TRPIS, M
   STROBERT, E
   CONSTANTINIDIS, I
   SWENSON, RB
TI ONCHOCERCA-VOLVULUS - PARASITOLOGICAL AND SEROLOGIC RESPONSES IN
   EXPERIMENTALLY INFECTED CHIMPANZEES AND MANGABEY MONKEYS
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE ONCHOCERCA VOLVULUS; NEMATODE; EXPERIMENTAL INFECTION; PRIMATES; PAN
   TROGLODYTES; CERCOCEBUS ATYS; ANTIBODY RESPONSES; MICROFILADERMIA
ID GUATEMALAN HUMAN ONCHOCERCIASIS; ANTIGENS; NODULES
AB Six chimpanzees (Pan troglodytes) and six mangabey monkeys (Cercocebus atys) were inoculated with Onchocerca volvulus third-stage larvae (L3) of West African origin. Two chimpanzees each received 200, 300, or 400 L3, while three mangabeys each received either 50 or 250 L3. All six chimpanzees became microfilaria positive between 11 and 25 months postinoculation (PI), while two of the six mangabeys were skin-snip positive at 24 and 37 months PI, respectively. All chimpanzees developed antibodies to two native antigens of 14 and 22 kDa and to the recombinant antigens OV16, OC3.6, and OC9.3. Marked antibody responses were observed in the mangabey monkeys, and in general, the responses were similar to those observed in the chimpanzees. However, in the mangabeys, these responses did not generally manifest themselves until later in the infection. The results of this study suggest that in chimpanzees, the smallest inoculum used, 200 L3, was sufficient to initiate consistent infections that had parasitologic and immunologic parameters equivalent to animals inoculated with larger numbers of larvae. Similarly, inoculation of mangabey monkeys with small numbers of larvae appeared to be as likely to establish infection and induce immunologic responses as did inoculation of larger numbers of larvae. Microfilaria-positive chimpanzees and mangabey monkeys were examined by three conventional imaging techniques (X ray, ultrasound, and magnetic resonance imaging (MRI)), but no adult worms or nodules could be identified in any animal. The detection of antibodies directed against both native and recombinant antigens suggests that certain of these responses might be useful for detecting early (prepatent) infections well before microfilariae appear in the skin and they might also be useful in detecting occult infections. The characterization of these responses in nonhuman primates provides a less complex system for interpreting the similar responses seen in humans living in onchocerciasis-endemic areas.
C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892.
   WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110.
   WASHINGTON UNIV,SCH MED,DEPT BIOL MOLEC,ST LOUIS,MO 63110.
   JOHNS HOPKINS MED INST,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205.
   EMORY UNIV,YERKES REG PRIMATE RES CTR,DEPT VET SCI,ATLANTA,GA 30333.
   EMORY UNIV,FREDERIK PHILIPS MAGNET RESONANCE RES CTR,DEPT RADIOL,ATLANTA,GA 30333.
RP EBERHARD, ML (reprint author), CTR DIS CONTROL & PREVENT,DIV PARASIT DIS F13,ATLANTA,GA 30333, USA.
FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [AI 22488]
NR 14
TC 12
Z9 12
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 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD MAY
PY 1995
VL 80
IS 3
BP 454
EP 462
DI 10.1006/expr.1995.1057
PG 9
WC Parasitology
SC Parasitology
GA QX230
UT WOS:A1995QX23000010
PM 7729480
ER

PT J
AU FELDER, CC
AF FELDER, CC
TI MUSCARINIC ACETYLCHOLINE-RECEPTORS - SIGNAL-TRANSDUCTION THROUGH
   MULTIPLE EFFECTORS
SO FASEB JOURNAL
LA English
DT Review
DE ADENYLATE CYCLASE; CALCIUM; PHOSPHOLIPASE A2; PHOSPHOLIPASE C; G-PROTEIN
ID PROTEIN-KINASE-C; ARACHIDONIC-ACID RELEASE; SITE-DIRECTED MUTAGENESIS;
   PHOSPHOLIPASE-D ACTIVITY; PHOSPHOINOSITIDE TURNOVER; ADENYLATE-CYCLASE;
   INTRACELLULAR CALCIUM; PAROTID-GLAND; CA2+ INFLUX; PHOSPHATIDYLINOSITOL
   4,5-BISPHOSPHATE
AB Muscarinic receptors regulate a number of important basic physiologic functions including heart rate and motor and sensory control as well as more complex behaviors including arousal, memory, and learning, Loss of muscarinic receptor number or function has been implicated in the etiology of several neurological disorders including Alzheimer's dementia, Down's syndrone, and Parkinson's disease. Muscarinic receptors transduce their signals by coupling with G-proteins, which then modulate the activity of a number of effector enzymes and ion channels, Five subtypes of muscarinic receptors (m1-m5) have been identified by molecular cloning and much has been learned about their distribution, pharmacology, and structure, Less is known about the molecular mechanisms of receptor-effector coupling and the biological role of each receptor subtype, The ectopic expression of genes encoding a single muscarinic receptor subtype in mammalian cell lines has provided an important model system in which to investigate receptor subtype-specific pharmacology and signal transduction. Expression models have revealed that single muscarinic receptor m1, m3, or m5 subtypes can activate multiple signaling effecters simultaneously including phospholipases A2, C, and D, as well as tyrosine kinase and a novel class of voltage-insensitive calcium channels, The m2 or m4 receptors have been shown to augment phospholipase A2 in addition to their established role as inhibitory receptors acting through the attenuation of adenylate cyclase, In addition to allowing investigations of the regulatory mechanisms of muscarinic receptors, expression models provide an excellent tool to investigate receptor-subtype specific physiology and pharmacology.
RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A-15,BETHESDA,MD 20892, USA.
NR 97
TC 372
Z9 390
U1 4
U2 26
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 MAY
PY 1995
VL 9
IS 8
BP 619
EP 625
PG 7
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA RC106
UT WOS:A1995RC10600007
PM 7768353
ER

PT J
AU SATO, K
   KASHIWAYA, Y
   KEON, CA
   TSUCHIYA, N
   KING, MT
   RADDA, GK
   CHANCE, B
   CLARKE, K
   VEECH, RL
AF SATO, K
   KASHIWAYA, Y
   KEON, CA
   TSUCHIYA, N
   KING, MT
   RADDA, GK
   CHANCE, B
   CLARKE, K
   VEECH, RL
TI INSULIN, KETONE-BODIES, AND MITOCHONDRIAL ENERGY TRANSDUCTION
SO FASEB JOURNAL
LA English
DT Article
DE TRICARBOXYLIC ACID CYCLE INTERMEDIATES; MITOCHONDRIAL REDOX STATES;
   DELTA-PH; E(MITO/CYTO), DELTA-G(ATP)
ID PHOSPHATE-TRANSPORT; TISSUES; RESPIRATION; METABOLISM; MECHANISM;
   MEMBRANE; KINETICS; PLASMA; CELLS
AB Addition of insulin or a physiological ratio of ketone bodies to buffer with 10 mM glucose increased efficiency (hydraulic work/energy from O-2 consumed) of working rat heart by 25%, and the two in combination increased efficiency by 36%. These additions increased the content of acetyl CoA by 9- to 18-fold, increased the contents of metabolites of the first third of the tricarboxylic acid (TCA) cycle 2- to 5-fold, and decreased succinate, oxaloacetate, and aspartate 2- to 3-fold. Succinyl CoA, fumarate, and malate were essentially unchanged. The changes in content of TCA metabolites resulted from a reduction of the free mitochondrial NAD couple by 2- to 10-fold and oxidation of the mitochondrial coenzyme Q couple by 2- to 4-fold. Cytosolic pH, measured using P-31-NMR spectra, was invariant at about 7.0. The total intracellular bicarbonate indicated an increase in mitochondrial pH from 7.1 with glucose to 7.2, 7.5, and 7.4 with insulin, ketones, and the combination, respectively. The decrease in Eh(7) of the mitochondrial NAD couple, Eh(NAD+/NADH)(7), from -280 to -300 mV and the increase in Eh(7) of the coenzyme Q couple, Eh(Q/QH2)(7), from -4 to +12 mV was equivalent to an increase from -53 kJ to -60 kJ/2 mol e in the reaction catalyzed by the mitochondrial NADH dehydrogenase multienzyme complex (EC 1.6.5.3). The increase in the redox energy of the mitochondrial cofactor couples paralleled the increase in the free energy of cytosolic ATP hydrolysis, Delta G(ATP). The potential of the mitochondrial relative to the cytosolic phases, E(mito/cyto), calculated from Delta G(ATP) and Delta pH on the assumption of a 4 H+ transfer for each ATP synthesized, was -143 mV during perfusion with glucose or glucose plus insulin, and decreased to -120 mV on addition of ketones. Viewed in this light, the moderate ketosis characteristic of prolonged fasting or type II diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.
C1 NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852.
   UNIV OXFORD,DEPT BIOCHEM,OXFORD OX1 3QU,ENGLAND.
   UNIV PENN,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104.
NR 51
TC 164
Z9 165
U1 2
U2 12
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 MAY
PY 1995
VL 9
IS 8
BP 651
EP 658
PG 8
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA RC106
UT WOS:A1995RC10600011
PM 7768357
ER

PT J
AU OBRIEN, JS
   CARSON, GS
   SEO, HC
   HIRAIWA, M
   WEILER, S
   TOMICH, JM
   BARRANGER, JA
   KAHN, M
   AZUMA, N
   KISHIMOTO, Y
AF OBRIEN, JS
   CARSON, GS
   SEO, HC
   HIRAIWA, M
   WEILER, S
   TOMICH, JM
   BARRANGER, JA
   KAHN, M
   AZUMA, N
   KISHIMOTO, Y
TI IDENTIFICATION OF THE NEUROTROPHIC FACTOR SEQUENCE OF PROSAPOSIN
SO FASEB JOURNAL
LA English
DT Article
DE NEURITE OUTGROWTH; RECEPTOR; SAPOSIN PEPTIDE
ID SPHINGOLIPID ACTIVATOR PROTEINS; SAPOSIN PROTEINS; GAUCHER DISEASE;
   SERTOLI CELLS; GANGLIOSIDES; DEFICIENCY; PRECURSOR; PATIENT
AB Prosaposin, recently identified as a neurotrophic factor (1), is the precursor of saposins A, B, C, and D. The neurotrophic activity of prosaposin resides in the saposin C domain. We have pinpointed the active sequence to a linear 12-mer located in the NH2-terminal sequence of saposin C (LIDNNKTEKEIL). Nanomolar concentrations of a 22-mer peptide encompassing this region stimulated neurite outgrowth and choline acetyltransferase activity, and prevented cell death in neuroblastoma cells. In primary cerebellar granule cells, the 22-mer also stimulated neurite outgrowth. Studies of the neuroblastoma line NS20Y using a radiolabeled 18-mer from the neurotrophic region identified a high-affinity (K-d = 70 pM) binding site indicative of receptor-ligand interaction. The 22-mer stimulated protein phosphorylation of several proteins, some of which were tyrosine-phosphorylated after brief exposure similar to saposin C. Circular dichroism studies demonstrated that the 22-mer was converted from a random to a helical structure by addition of ganglioside GM(1). The results are consistent with receptor-ligand binding by the peptide initiating a signal transduction cascade and resulting in neuronal differentiation.
C1 NHLBI,BETHESDA,MD 20892.
   KANSAS STATE UNIV AGR & APPL SCI,DEPT BIOCHEM,MANHATTAN,KS 66506.
   UNIV PITTSBURGH,DEPT HUMAN GENET,GENET MOLEC LAB,PITTSBURGH,PA 15261.
   UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT PATHOBIOL,SEATTLE,WA 98195.
RP OBRIEN, JS (reprint author), UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,DEPT NEUROSCI,LA JOLLA,CA 92093, USA.
FU NIDDK NIH HHS [DK43709]; NINDS NIH HHS [NS13559, NS08682]
NR 27
TC 104
Z9 105
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 MAY
PY 1995
VL 9
IS 8
BP 681
EP 685
PG 5
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA RC106
UT WOS:A1995RC10600015
PM 7768361
ER

PT J
AU EMMERTBUCK, MR
   EMONARD, HP
   CORCORAN, ML
   KRUTZSCH, HC
   FOIDART, JM
   STETLERSTEVENSON, WG
AF EMMERTBUCK, MR
   EMONARD, HP
   CORCORAN, ML
   KRUTZSCH, HC
   FOIDART, JM
   STETLERSTEVENSON, WG
TI CELL-SURFACE BINDING OF TIMP-2 AND PRO-MMP-2/TIMP-2 COMPLEX
SO FEBS LETTERS
LA English
DT Article
DE METALLOPROTEINASE; TUMOR CELL; INVASION; ACTIVATION; TISSUE INHIBITOR;
   TIMP-2
ID HUMAN 72-KDA GELATINASE; TISSUE INHIBITOR; IV COLLAGENASE; MATRIX
   METALLOPROTEINASES; MESSENGER-RNAS; EXPRESSION; IDENTIFICATION; MEMBER;
   FAMILY; SITE
AB Tissue inhibitor of metalloproteinases (TIMP-2) is a low molecular weight proteinase inhibitor capable of inhibiting activated matrix metalloproteinases (MMPs). TIMP-2 is found both free and in a 1:1 stoichiometric complex with the pro-enzyme form of MMP-2 (pro-MMP-2/TIMP-2 complex). We have measured the binding of recombinant TIMP-2 to intact HT-1080 and MCF-7 cells, HT-1080 cells in suspension bound I-125-labeled rTIMP-2 with a K-d of 2.5 nM and 30,000 sites/cell. Monolayers of MCF-7 cells were similarly found to bind [I-125]rTIMP-2 with a K-d of 1.6 nM and 25,000 sites/cell. Specific binding of MMP-2 alone to HT-1080 cells was not observed; however, pro-MMP-2/TIMP-2 complex was capable of binding to the surface of HT-1080 cells in a TIMP-2-dependent manner. Binding of rTIMP-2 was not competed by the presence of TIMP-1. These results suggest that rTIMP-2 alone binds directly to the cell surface of HT-1080 and MCF-7 cell lines, and TIMP-2 is capable of localizing MMP-2 to the surface of HT-1080 cells via interaction with a specific binding site.
C1 NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,BETHESDA,MD 20892.
   UNIV LIEGE,BIOL LAB,LIEGE,BELGIUM.
RI Stetler-Stevenson, William/H-6956-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808
NR 26
TC 90
Z9 90
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD MAY 1
PY 1995
VL 364
IS 1
BP 28
EP 32
DI 10.1016/0014-5793(95)00345-A
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA QW545
UT WOS:A1995QW54500007
PM 7750537
ER

EF