FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Kennison, JA Vazquez, M Brizuela, BJ AF Kennison, JA Vazquez, M Brizuela, BJ BE Kukuruzinska, MA Tabak, LA TI Regulation of the Sex combs reduced gene in Drosophila SO SALIVARY GLAND BIOGENESIS AND FUNCTION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Salivary Gland Biogenesis and Function CY NOV 07-10, 1996 CL ARLIE, VA SP NIDR ID NUCLEOSOME REMODELING FACTOR; HOMEOTIC GENES; TRANSCRIPTIONAL ACTIVATION; MULTISUBUNIT COMPLEX; BINDING PROTEIN; FUSHI-TARAZU; BRAHMA GENE; DNA-BINDING; MELANOGASTER; YEAST AB The Sex combs reduced gene of the Antennapedia complex specifies the identities of the anterior thoracic and posterior head segments, including the primordium of the larval salivary gland. The Sex combs reduced transcription unit spans over 30 kb of genomic DNA, with another 40 kh of upstream cis-regulatory sequences. The pattern of Sexcombs reduced transcription is set in the early embryo by the segmentation genes and is then maintained by two competing sets of proteins, the Polycomb group and the trithorax group. One of the trithorax group genes required for activation, the brahma gene, encodes an evolutionarily conserved DNA-stimulated ATPase that is part of a large protein complex. This complex facilitates the action of sequence-specific, DNA-bindifig proteins in regulating target genes, possibly by altering chromatin structure. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Genet & Fisiol Mol, Cuernavaca 62250, Morelos, Mexico. Univ Calif Los Angeles, Dept Biol Chem, Howard Hughes Med Inst, Los Angeles, CA 90024 USA. RP Kennison, JA (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM jkl5o@nih.gov NR 63 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-136-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 842 BP 28 EP 35 DI 10.1111/j.1749-6632.1998.tb09628.x PG 8 WC Dentistry, Oral Surgery & Medicine; Substance Abuse; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Substance Abuse; Science & Technology - Other Topics GA BL11Q UT WOS:000074330900005 PM 9599290 ER PT S AU Lafrenie, RM Yamada, KM AF Lafrenie, RM Yamada, KM BE Kukuruzinska, MA Tabak, LA TI Integrins and matrix molecules in salivary gland cell adhesion, signaling, and gene expression SO SALIVARY GLAND BIOGENESIS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Salivary Gland Biogenesis and Function CY NOV 07-10, 1996 CL ARLIE, VIRGINIA SP NIDR ID EXTRACELLULAR-MATRIX; GROWTH-FACTOR; DIFFERENTIATION; PROTEIN; DECARBOXYLASE; TRANSDUCTION; ACTIVATION; PATHWAYS AB Integrins play crucial roles in embryonic and adult cell adhesion, migration, morphogenesis, growth, and differentiation in many cell systems, including human salivary gland cells, Integrins function by binding through their extracellular domain to a specific peptide recognition site in a ligand, and then transmitting information to the cytoplasm by nay of their cytoplasmic tails, By this transmembrane signaling process, integrins can mediate assembly of adhesion sites and organization of the actin-containing cytoskeleton by forming supermolecular complexes of cytoskeletal and signaling molecules. The specific steps in the assembly of these complexes as well as novel mechanisms for synergy between integrin and growth factor signaling pathways are still being determined. Integrin-mediated interactions also have major effects on gene expression, For example, integrin-mediated adhesion to fibronectin by the HSG salivary gland cell line significantly alters the pattern of proteins synthesized and genes expressed. In fact, at least five transcription factors are activated, and over 30 genes (many of them novel) are found to be induced by such integrin-mediated interactions by salivary eland cells. The roles of integrins, in collaborative interactions with growth factors and signaling pathways, and in the induction of novel genes during salivary gland development, should provide fruitful areas of research for many years. C1 NE Ontario Reg Canc Ctr, Sudbury, ON P3E 5J1, Canada. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Lafrenie, RM (reprint author), NE Ontario Reg Canc Ctr, 41 Ramsey Lake Rd, Sudbury, ON P3E 5J1, Canada. EM robert_lafrenie@cancercare.on.ca OI Yamada, Kenneth/0000-0003-1512-6805 NR 31 TC 24 Z9 24 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-135-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 842 BP 42 EP 48 DI 10.1111/j.1749-6632.1998.tb09630.x PG 7 WC Dentistry, Oral Surgery & Medicine; Substance Abuse; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Substance Abuse; Science & Technology - Other Topics GA BL11Q UT WOS:000074330900007 PM 9599292 ER PT S AU Fox, PC AF Fox, PC BE Kukuruzinska, MA Tabak, LA TI Acquired salivary dysfunction - Drugs and radiation SO SALIVARY GLAND BIOGENESIS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Salivary Gland Biogenesis and Function CY NOV 07-10, 1996 CL ARLIE, VIRGINIA SP NIDR ID INDUCED XEROSTOMIA; ORAL PILOCARPINE; X-IRRADIATION; NECK-CANCER; GLANDS; HEAD; SIALOCHEMISTRY; FLOW AB When considering the effects of drugs on salivary glands, a distinction should be drawn between the complaint of oral dryness (xerostomia), a symptom, and measurable secretory hypofunction, a sign. In general, the symptom of xerostomia is often not accompanied by objective reductions in salivary output, and xerostomia is not a reliable indicator of secretory hypofunction. Whereas therapeutic pharmaceutical side effects represent the most prominent cause of xerostomia, with over 500 drugs associated with this symptom, only a small number of drugs have been demonstrated to reduce salivary output substantially. There are examples in which drugs with a high prevalence of xerostomia complaints do not affect secretory function. The mechanisms responsible for this discrepancy between subjective and objective findings have not been fully identified. It is hypothesized that alterations in systemic or mucosal hydration may play a role. Of the drugs with true salivary hypofunctional actions, most have direct anticholinergic properties. In almost all cases, the salivary effects of pharmaceuticals are not permanent, and function returns to pretreatment levels when the medication is stopped. By contrast, the effects of irradiation on the salivary glands are permanent when exposures exceed 50 Gy. About 40,000 individuals per year receive irradiation that involves the salivary glands (by external beam or internal sources-radon implants and I-131) Tor treatment of cancers of the head and neck region. Although these radiation effects have been recognized as a significant clinical problem for more than SO Sears, the specific mechanisms responsible for radiation-induced salivary gland dysfunction are still not understood. With the exception of studies documenting the secretory functional deficits following head and neck irradiation, limited studies have been done in humans. The majority of experimental work has been done in rodents. A variety of mechanisms, including mitotic and interphase fell death, direct DNA damage or effects of secondary metabolites, damage to progenitor cells, or altered gene expression, have an been proposed to explain tire salivary epithelial cell death observed. Recent experimental studies with models of radiation-induced salivary damage in rats and a human salivary cell line suggest that the small percentage of surviving epithelial cells are capable of performing functions such as signal transduction and ion transport normally Apoptotic cell death following irradiation has not been a prominent feature in these model systems. The effects of head and neck radiation on the salivary glands and oral cavity continue to present multiple significant clinical problems both during and after radiotherapy. In recent Sears, there has been some progress in minimizing these effects through more careful shielding and pretreatment planning. Additionally, there are preliminary results from a clinical trial suggesting that the use of a secretagogue, pilocarpine HCl, given during the course of radiotherapy, may reduce the secretory hypofunctional effects. A multicenter trial is nom underway to test this hypothesis. There is still a real need to develop more effective treatments for this condition. C1 NIDR, Clin Invest Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Fox, PC (reprint author), NIDR, Clin Invest Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N-113,10 Ctr Dr MSC 1190, Bethesda, MD 20892 USA. NR 26 TC 72 Z9 74 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-135-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 842 BP 132 EP 137 DI 10.1111/j.1749-6632.1998.tb09641.x PG 6 WC Dentistry, Oral Surgery & Medicine; Substance Abuse; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Substance Abuse; Science & Technology - Other Topics GA BL11Q UT WOS:000074330900018 PM 9599303 ER PT S AU O'Connell, BC Lillibridge, CD Ambudkar, I Kruse, D AF O'Connell, BC Lillibridge, CD Ambudkar, I Kruse, D BE Kukuruzinska, MA Tabak, LA TI Somatic gene transfer to salivary glands SO SALIVARY GLAND BIOGENESIS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Salivary Gland Biogenesis and Function CY NOV 07-10, 1996 CL ARLIE, VIRGINIA SP NIDR ID IN-VIVO; RECOMBINANT ADENOVIRUSES; IMMUNE-RESPONSES; THERAPY; EXPRESSION; DELIVERY; VECTORS; MOUSE; CELLS; INDUCTION AB Recent developments in gene transfer technology have expanded the range of in vivo experimentation and provided new insights that might be applicable to the treatment of human diseases. Somatic gene transfer may complement conventional transgenic animal experiments by allowing for more restricted gene expression. Salivary glands of rats are readily transduced in vivo by adenovirus vectors. This model has been used to demonstrate the effects of transferring a water channel (aquaporin) gene to glands that have been damaged by radiation. Submandibular glands that receive the aquaporin vector increase the stimulated salivary flow close to normal levels. The possible role of E2F1 in promoting cell regeneration in vivo was also explored. A vector expressing E2F1 was capable of increasing DNA synthesis in rat salivary glands, though complete mitosis was not observed. Future generations of vectors must overcome current limitations of efficiency, immunogenicity, and transient expression. C1 NIDR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Oral Pathol Res Lab, Washington, DC 20422 USA. RP O'Connell, BC (reprint author), NIDR, Gene Therapy & Therapeut Branch, NIH, Bldg 10-1N113,10 Ctr Dr, Bethesda, MD 20892 USA. EM oconnell@yoda.nidr.nih.gov OI O'Connell, Brian/0000-0003-4529-7664 NR 44 TC 5 Z9 5 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-135-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 842 BP 171 EP 180 DI 10.1111/j.1749-6632.1998.tb09645.x PG 10 WC Dentistry, Oral Surgery & Medicine; Substance Abuse; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Substance Abuse; Science & Technology - Other Topics GA BL11Q UT WOS:000074330900022 PM 9599307 ER PT S AU Furth, PA Li, ML Hennighausen, L AF Furth, PA Li, ML Hennighausen, L BE Kukuruzinska, MA Tabak, LA TI Studying development of disease through temporally controlled gene expression in the salivary gland SO SALIVARY GLAND BIOGENESIS AND FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Salivary Gland Biogenesis and Function CY NOV 07-10, 1996 CL ARLIE, VIRGINIA SP NIDR ID SV40 T-ANTIGEN; TETRACYCLINE-RESPONSIVE PROMOTER; TRANSGENIC MICE; MAMMALIAN-CELLS; IN-VIVO; TUMORIGENESIS; PROGRESSION; APOPTOSIS; ONCOGENE; GROWTH AB Multistep tumorigenesis proceeds through activation of oncogenes and inactivation of tumor suppressor genes, Initiating oncoproteins induce secondary changes that maintain transformation in the absence of original stimuli. Time-dependent reversal of SV40 T antigen (TAg)-induced hyperplasia was studied using temporally controlled gene expression. Targeting TAg expression to the submandibular salivary gland of transgenic mice produces focal hyperplasias at age two weeks, which extend through large areas of the gland by four months. At twelve months, fibrosis and tumor foci accompany hyperplasia, Hyperplasia reverses when TAg expression is discontinued at four months but not at seven months. Secondary changes that maintain transformation appear to be rime dependent. The system can be used to identify genetic events resulting in phenotypic: reversal at four months and to expose factors preventing its occurrence at seven months. Expression of other proteins can be targeted to the salivary gland, and temporally controlled gene deletions can also be made using this system. C1 Inst Human Virol, Ctr Med Biotechnol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. Balimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Natl Inst Diabet & Digest Dis, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Furth, PA (reprint author), Inst Human Virol, Ctr Med Biotechnol, 725 W Lombard St,Room 545, Baltimore, MD 21201 USA. NR 32 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-135-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 842 BP 181 EP 187 DI 10.1111/j.1749-6632.1998.tb09646.x PG 7 WC Dentistry, Oral Surgery & Medicine; Substance Abuse; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Substance Abuse; Science & Technology - Other Topics GA BL11Q UT WOS:000074330900023 PM 9599308 ER PT J AU Milne, GWA Nicklaus, MC Wang, S AF Milne, GWA Nicklaus, MC Wang, S TI Pharmacophores in drug design and discovery SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE pharmacophores; drugs; inhibitors; molecular modeling; enzymes ID GENERATED CHEMICAL STRUCTURES; NATIONAL-CANCER-INSTITUTE; RAY CRYSTALLOGRAPHIC DATA; PROTEIN-KINASE-C; INFORMATION-SYSTEM; HIV-1 REPLICATION; INHIBITION; MOLECULES; CAMBRIDGE; BINDING AB Compounds containing a specific pharmacophore - the minimum structural features necessary for enzyme binding - can be retrieved from a database such as the National Cancer Institute repository by means of three-dimensional (3D) searching, which allows the retrieval of all compounds possessing a specified set of atoms with a given 3D geometry. The ways in which pharmacophores can be found and characterized and the details of the 3D searching methods are described. Elaboration of compounds found in such searches and their subsequent development as lead drugs is also discussed. C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Milne, GWA (reprint author), NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RI Nicklaus, Marc/N-4183-2014 NR 28 TC 26 Z9 26 U1 0 U2 3 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PY 1998 VL 9 IS 1-2 BP 23 EP + DI 10.1080/10629369808039147 PG 19 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 115RE UT WOS:000075678300002 PM 9517013 ER PT J AU Benton, D AF Benton, D TI Integrated access to genomic and other bioinformation: An essential ingredient of the drug discovery process SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE biological databases; information retrieval; heterogeneous databases; database federation ID PROTEIN-SEQUENCE DATABASE; DATA-BANK; TRANSCRIPTION FACTORS; RETRIEVAL-SYSTEM; DATA-BASE; CLASSIFICATION; GENES; SACCHAROMYCES; COLLECTION; FERMENTS AB Due to the high rate of data production and the need of researchers to have rapid access to new data, public databases have become the major medium through which genome mapping and sequencing data as well as macromolecular structural data are published. There are now more than 250 databases of biomolecular, structural, genetic, or phenotypic data, many of which are doubling in size annually. These databases, many of which were created and are maintained by experimentalists for their own research use, provide valuable collections of organized, validated data. However, the very number and diversity of databases now make efficient data resource discovery as important as effective data resource use. Existing autonomous biological databases contain related data which are more valuable when interconnected than when isolated. Political and scientific realities dictate that these databases will be built by different teams, in different locations, for different purposes, and using different data models and supporting DBMSs. As a consequence, connecting the related data they contain is not straightforward. Experience with existing biological databases indicates that it is possible to form useful queries across these databases, but that doing so usually requires expertise in the semantic structure of each source database. Advancing to the next level of integration among biological information resources poses significant technical and sociological challenges. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Benton, D (reprint author), SmithKline Beecham Pharmaceut, Adv Informat Technol Dept, Mail Stop UW2230,709 Swedeland Rd,POB 1539, King Of Prussia, PA 19406 USA. NR 95 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PY 1998 VL 8 IS 3-4 BP 121 EP 155 DI 10.1080/10629369808039138 PG 35 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 115RD UT WOS:000075678200001 PM 9522473 ER PT J AU Blair, A Stewart, PA Zaebst, DD Pottern, L Zey, JN Bloom, TF Miller, B Ward, E Lubin, J AF Blair, A Stewart, PA Zaebst, DD Pottern, L Zey, JN Bloom, TF Miller, B Ward, E Lubin, J TI Mortality of industrial workers exposed to acrylonitrile SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE cancer; cohort study; industrial workers; lung cancer; nested case-control study ID CANCER INCIDENCE; LUNG-CANCER; DIMETHYLFORMAMIDE; RISKS AB Objectives This study was designed to evaluate the relationship between occupational exposure to acrylonitrile and cancer mortality. Materials and methods Workers(18079 white men, 4293 white women, 2191 nonwhite men, and 897 nonwhite women) employed in acrylonitrile production or use in the 1950s through 1983 were followed through 1989 for vital status and cause of death. Exposure-response relationships were evaluated from quantitative estimates of historical exposures. Tobacco use was determined for a sample of workers to assess potential confounding. Mortality rates between the exposed and unexposed workers in the cohort were compared using the Poisson regression. Results Analyses by cumulative, average, peak, intensity, duration, and lagged exposure revealed no elevated risk of cancers of the stomach, brain, breast, prostate or lymphatic and hematopoietic systems. Mortality from lung cancer was elevated for the highest quintile of cumulative exposure. When the decile categories were used, the relative risk did not continue to increase at higher levels. Adjustment for cigarette use reduced the risk for lung cancer only slightly. Separate analyses for wage and salaried workers, long-term and short-term workers, fiber and nonfiber plants, and individual plants revealed no clear exposure-response patterns. Conclusions The results indicate that exposure to acrylonitrile at the levels studied is not associated with an increased relative risk for most cancers of a priori interest. The excess of lung cancer in the highest quintile of cumulative exposure may indicate carcinogenic activity at the highest levels of exposure, but analyses of exposure-response do not provide strong or consistent evidence for a causal association. C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Cent Missouri State Univ, Warrensburg, MO 64093 USA. NIOSH, Hlth Related Energy Res Branch, Cincinnati, OH 45226 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. NIOSH, Industrywide Studies Branch, Cincinnati, OH 45226 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Occupat Epidemiol Branch, Execut Pl N,Room 418, Bethesda, MD 20892 USA. NR 44 TC 55 Z9 56 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 PY 1998 VL 24 SU 2 BP 25 EP 41 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 106VG UT WOS:000075170700005 PM 9714511 ER PT J AU Stewart, PA Zaebst, D Zey, JN Herrick, R Dosemeci, M Hornung, R Bloom, T Pottern, L Miller, BA Blair, A AF Stewart, PA Zaebst, D Zey, JN Herrick, R Dosemeci, M Hornung, R Bloom, T Pottern, L Miller, BA Blair, A TI Exposure assessment for a study of workers exposed to acrylonitrile SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE cancer; occupation AB Procedures used to develop estimates of exposure to acrylonitrile for a cohort study (>25000 workers in 8 monomer, fiber, and resin companies from 1952 to 1953) are presented. Visits to the companies were made, interviews of workers were conducted historical records were made, and measurements were taken. On the basis of similar tasks, locations, other exposures, and a similar distribution of exposures to acrylonitrile, 3600 exposure groups were formed. Special procedures were used to reduce the misclassification of workers performing tasks that varied in lime but that were inadequately reflected in the job title. A software program organized and retained all exposure information on each exposure group. Quantitative estimates of acrylonitrile exposure were developed using a hierarchical approach in a software program that documented the derivation of each estimate and facilitated data review. Two of the estimation methods were evaluated in a comparison with measurement data. C1 NCI, Bethesda, MD 20892 USA. NIOSH, Cincinnati, OH 45226 USA. RP Stewart, PA (reprint author), NCI, EPN 418,6130 Execut Blvd MSC 7364, Bethesda, MD 20892 USA. NR 20 TC 19 Z9 19 U1 0 U2 3 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 PY 1998 VL 24 SU 2 BP 42 EP 53 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 106VG UT WOS:000075170700006 PM 9714512 ER PT J AU Shore, D AF Shore, D TI Recent developments in atypical antipsychotic medications SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material C1 NIMH, NIH, Rockville, MD 20857 USA. RP Shore, D (reprint author), NIMH, NIH, Rockville, MD 20857 USA. NR 3 TC 3 Z9 3 U1 1 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1998 VL 24 IS 1 BP 33 EP 33 PG 1 WC Psychiatry SC Psychiatry GA YX608 UT WOS:000072057700008 PM 9502544 ER PT J AU Weickert, CS Weinberger, DR AF Weickert, CS Weinberger, DR TI A candidate molecule approach to defining developmental pathology in schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Review DE puberty; hormone receptors; growth factors; myelination ID PRIMATE CEREBRAL-CORTEX; CENTRAL-NERVOUS-SYSTEM; MEDIAL TEMPORAL-LOBE; HUMAN-BRAIN; CORTICAL DEVELOPMENT; GROWTH-FACTOR; PREFRONTAL CORTEX; GENE-EXPRESSION; THYROID-HORMONE; NEURONAL GROWTH AB The evidence that schizophrenia may have its origins from early in life, possibly during prenatal brain development, is based primarily on a constellation of nonspecific anatomical findings and on the results of surveys of obstetrical complications and of childhood neurological and psychological adjustment. The developmental processes implicated by this evidence are uncertain, but speculation has centered around abnormalities of neuronal proliferation, migration, and connection formation. These developmental milestones are the results of complicated cellular processes involving molecular interactions between cells and between the extracellular and intracellular milieus. To understand how these abnormalities could relate to schizophrenia, it is necessary to characterize the molecular events that define the processes. In this article, we discuss the potential impact of a number of molecules that are important in the sequence of cellular events implicated in schizophrenia. In particular, we focus on molecular mechanisms related to cell proliferation, axonal outgrowth, cen migration, cell survival, synaptic regression, myelination, and developmental aspects of early adult life, These various candidate molecules regulate different aspects of cell growth and cell-cell interactions and are involved in the regulation of deoxyribonucleic acid (DNA) expression. Very few of these molecules have been studied in the schizophrenic brain. C1 NIMH, St Elizabeths Hosp, Ctr Neurosci, Intramural Res Program,Clin Brain Disorders Branc, Washington, DC 20032 USA. RP Weinberger, DR (reprint author), NIMH, NIH, Clin Brain Disorders Branch, IRP,Neurosci Ctr St Elizabeths, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. RI Shannon Weickert, Cynthia/G-3171-2011 NR 161 TC 39 Z9 39 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1998 VL 24 IS 2 BP 303 EP 316 PG 14 WC Psychiatry SC Psychiatry GA ZQ561 UT WOS:000073880400010 PM 9613627 ER PT J AU Shore, D Hsiao, JK Keith, SJ Regier, D AF Shore, D Hsiao, JK Keith, SJ Regier, D TI In Memoriam - Barbara Bruner SO SCHIZOPHRENIA BULLETIN LA English DT Biographical-Item C1 NIMH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1998 VL 24 IS 3 BP COVER2 EP COVER2 PG 1 WC Psychiatry SC Psychiatry GA 111JK UT WOS:000075433400001 ER PT J AU Torrey, EF Yolken, RH AF Torrey, EF Yolken, RH TI Is household crowding a risk factor for schizophrenia? SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 St Elizabeth Hosp, Ctr Neurosci, NIMH, Washington, DC 20032 USA. Johns Hopkins Univ, Med Ctr, Stanley Neurovirol Lab, Baltimore, MD 21218 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 12 EP 13 DI 10.1016/S0920-9964(97)88316-8 PG 2 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000020 ER PT J AU Kumra, S Wiggs, E Bedwell, J Asarnow, RF Rapoport, JL AF Kumra, S Wiggs, E Bedwell, J Asarnow, RF Rapoport, JL TI Comparison of neuropsychological deficits in childhood-onset schizophrenia and multidimensionally impaired syndrome SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, NIMH, Child Psychiat Branch, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 58 EP 58 DI 10.1016/S0920-9964(97)88438-1 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000143 ER PT J AU Bigelow, LB Torrey, EF AF Bigelow, LB Torrey, EF TI Post-mortem brain weight in schizophrenia and affective disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 85 EP 85 DI 10.1016/S0920-9964(97)88511-8 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000214 ER PT J AU Torrey, EF Yolken, RH Zito, M Heyes, M AF Torrey, EF Yolken, RH Zito, M Heyes, M TI Increased CSF and brain quinolinic acid in schizophrenia and bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, St Elizabeths Hosp, Ctr Neurosci, Washington, DC 20032 USA. Johns Hopkins Univ, Med Ctr, Stanley Neurovirol Lab, Baltimore, MD 21218 USA. NIMH, Clin Sci Lab, Rockville, MD 20857 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 91 EP 92 DI 10.1016/S0920-9964(97)88530-1 PG 2 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000234 ER PT J AU Freed, WJ Vawter, M AF Freed, WJ Vawter, M TI N-CAM abnormalities in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIDA, IRP, Baltimore, MD USA. NIMH, Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 101 EP 102 DI 10.1016/S0920-9964(97)88557-X PG 2 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000261 ER PT J AU Hamid, EH Hyde, TM Egan, MF Bachus, SE Kinkead, BL Nemeroff, CB Wolf, SS Herman, MM Kleinman, JE AF Hamid, EH Hyde, TM Egan, MF Bachus, SE Kinkead, BL Nemeroff, CB Wolf, SS Herman, MM Kleinman, JE TI Abnormalities in neurotensin gene expression levels in the hippocampus of schizophrenics SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Neurosci Ctr St Elizabeths, IRP, Washington, DC 20032 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 102 EP 103 DI 10.1016/S0920-9964(97)88560-X PG 2 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000264 ER PT J AU Kumra, S Krasnewich, D Rapoport, JL AF Kumra, S Krasnewich, D Rapoport, JL TI Association of sex chromosome anomalies with childhood-onset psychotic disorders SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 141 EP 141 DI 10.1016/S0920-9964(97)88660-4 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000363 ER PT J AU Kumra, S Jacobsen, LK Rapoport, JL AF Kumra, S Jacobsen, LK Rapoport, JL TI Childhood-onset schizophrenia: An open-label study of olanzapine in adolescents SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 149 EP 149 DI 10.1016/S0920-9964(97)88679-3 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000383 ER PT J AU Raedler, TJ Knable, MB Lafargue, T Pickar, D Weinberger, DR AF Raedler, TJ Knable, MB Lafargue, T Pickar, D Weinberger, DR TI Striatal dopamine D2 receptor occupancy in patients treated with olanzapine SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 166 EP 166 DI 10.1016/S0920-9964(97)88730-0 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000433 ER PT J AU Kumra, S Jacobsen, LK Rapoport, JL AF Kumra, S Jacobsen, LK Rapoport, JL TI The spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1998 VL 29 IS 1-2 BP 177 EP 177 DI 10.1016/S0920-9964(97)88757-9 PG 1 WC Psychiatry SC Psychiatry GA YV527 UT WOS:000071834000462 ER PT J AU Thorgeirsson, SS Teramoto, T Factor, VM AF Thorgeirsson, SS Teramoto, T Factor, VM TI Dysregulation of apoptosis in hepatocellular carcinoma SO SEMINARS IN LIVER DISEASE LA English DT Review DE apoptosis; TGF-beta; liver; carcinoma; proliferation ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 TGF-BETA-1; INSULIN-RECEPTOR SUBSTRATE-1; TUMOR-SUPPRESSOR GENE; IN-VIVO ALTERATIONS; HUMAN LUNG CANCERS; TGF-BETA; II RECEPTOR; LIVER CARCINOGENESIS; FETAL HEPATOCYTES AB The tightly controlled homeostatic mechanisms between cell growth and apoptosis that exist in normal liver tissue are disrupted during hepatocarcinogenesis. The TGF (transforming growth factor)-beta signaling system is a central component of the mechanisms by which cell growth and apoptosis are controlled in the liver. The recent delineation of the TGF-beta signaling pathway has provided a unique framework for analysis of the impact that disruption of individual components of this signaling pathway can have on apoptosis during hepatocarcinogenesis. Here we review recent data on involvement of the TGF-beta signaling pathway in the dysregulation of apoptosis frequently observed in hepatocellular carcinomas. The data indicate that disruption of the TGF-beta pathway at the pre-receptor receptor and post-receptor levels occurs in hepatocellular carcinomas and can cause dysregulation of apoptosis. Also, substantial evidence now exists that phosphatidylinositol-3-kinase (PI3K) may function as an important negative regulator of the TGF-beta 1-induced apoptosis in hepatocellular carcinomas. Taken together, the available evidence indicates that disruption of the TGF-beta 1-induced apoptosis as well as growth inhibition is an important and integral part of the multistage process of liver carcinogenesis. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37,Rm 3C28,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 68 TC 63 Z9 64 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PY 1998 VL 18 IS 2 BP 115 EP 122 DI 10.1055/s-2007-1007148 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 176BR UT WOS:000079131100003 PM 9606809 ER PT S AU Monaco, MCG Shin, J Major, EO AF Monaco, MCG Shin, J Major, EO BE Brown, F Lewis, AM TI JC virus infection in cells from lymphoid tissue SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM DE peripheral lymphocytes; B cells; JCV; T and V antigens ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN POLYOMAVIRUS; B-LYMPHOCYTES; BONE-MARROW; DNA; PATHOGENESIS; BRAIN AB Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease characterized by infection of oligodendrocytes by JC virus. The exact nature of the pathogenesis of PML is not known. The nature of the primary infection, the site of viral latency, and the route by which JCV enters the brain remain to be elucidated. Different laboratories have shown the presence of JCV in peripheral lymphocytes from immunosuppressed individuals, suggesting these cells as possible carriers of JCV to the brain. To examine this observation, we tested the susceptibility to JCV infection of cells from lymphoid organs, focusing our attention on CD34+ haematopoietic precursor cells and B lymphocytes. The results demonstrate that both these cell types are susceptible to JCV infection and, moreover, that JCV can infect only those cells that differentiate into lymphocytic lineage. C1 NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Monaco, MCG (reprint author), NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 15 TC 23 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 115 EP 122 PG 8 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300014 PM 9776232 ER PT S AU Pass, H Rizzo, P Donington, J Wu, P Carbone, M AF Pass, H Rizzo, P Donington, J Wu, P Carbone, M BE Brown, F Lewis, AM TI Further validation of SV40-like DNA in human pleural mesotheliomas SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM AB We have confirmed in a second set of patients having human pleural mesothelioma that DNA for regions of the amino terminus of SV40 Tag can be amplified by the polymerase chain reaction. Moreover, other regions, including the carboxy terminus for Tag, and the regulatory region of SV40, are present in these specimens. C1 NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. Loyola Univ, Dept Pathol, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Chicago, IL 60611 USA. RP Pass, H (reprint author), Harper Grace Hosp, Karmanos Canc Inst, 3990 John R,Suite 2102, Detroit, MI 48201 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 143 EP 145 PG 3 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300017 PM 9776235 ER PT S AU Fried, M Carbone, M Shah, K Tognon, M Lednicky, J Fanning, E de Villiers, EM Villarreal, L Oxman, M Butel, J Strickler, H Garcea, R Martin, R Procopio, A Goedert, J Weber, T Loe-Fisher, B Kyle, W Bergsagel, J Urnovitz, H Pass, H Weiss, R Gibbs, A Ratner, H AF Fried, M Carbone, M Shah, K Tognon, M Lednicky, J Fanning, E de Villiers, EM Villarreal, L Oxman, M Butel, J Strickler, H Garcea, R Martin, R Procopio, A Goedert, J Weber, T Loe-Fisher, B Kyle, W Bergsagel, J Urnovitz, H Pass, H Weiss, R Gibbs, A Ratner, H BE Brown, F Lewis, AM TI Issues related to the detection of SV40 DNA in human tissues - Panel-audience discussion I SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 Imperial Canc Res Fund, London WC2A 3PX, England. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, Baltimore, MD 21205 USA. Sch Med, Inst Histol, I-44100 Ferrara, Italy. Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. Div Tumourvirus, D-69120 Heidelberg, Germany. Univ Calif Irvine, Irvine, CA 92697 USA. Univ Calif San Diego, Med Ctr, Infect Dis Sect, La Jolla, CA 92161 USA. Baylor Univ, Div Mol Virol, Houston, TX 77030 USA. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Univ Colorado, Dept Pediat, Denver, CO 80262 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ G DAnnunzio, I-66013 Chieti, Italy. NCI, Rockville, MD 20852 USA. Marienkrankenhaus Hamburg, Neurol Klin, D-22087 Hamburg, Germany. Univ Colorado, Dept Pediat, Denver, CO 80262 USA. Amer Soc Microbiol, Hingham, MA 02043 USA. Scottish Rite Hosp, Atlanta, GA 30342 USA. Chron Illness Res Found, San Francisco, CA 94121 USA. Harper Grace Hosp, Ctr Inst, Detroit, MI 48201 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Llandough Hosp NHS Trust, Dept Histopathol, Penarth CF64 2XX, S Glam, Wales. Child & Family Quarterly, Oak Pk, IL 60603 USA. RP Fried, M (reprint author), Imperial Canc Res Fund, 44 Lincolns Inn Fields, London WC2A 3PX, England. NR 0 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 165 EP 180 PG 16 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300021 ER PT S AU Strickler, HD Goedert, JJ AF Strickler, HD Goedert, JJ BE Brown, F Lewis, AM TI Exposure to SV40-contaminated poliovirus vaccine and the risk of cancer - A review of the epidemiological evidence SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM ID HUMAN PLEURAL MESOTHELIOMA; HUMAN BRAIN-TUMORS; LARGE T-ANTIGEN; SIMIAN VIRUS-40; CHOROID-PLEXUS; DNA-SEQUENCES; SV40; CHILDHOOD C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, NIH, 6130 Execut Blvd,EPN 434, Rockville, MD 20852 USA. NR 26 TC 23 Z9 23 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 235 EP 244 PG 10 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300028 PM 9776245 ER PT S AU Levine, AS AF Levine, AS BE Brown, F Lewis, AM TI SV40 as a putative human commensal - Opening remarks SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Levine, AS (reprint author), NICHHD, NIH, Bldg 31,Rm 2A50, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 247 EP 249 PG 3 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300029 ER PT S AU Shah, K Levine, A Butel, J Urnovitz, H Pass, H Goedert, J Dorries, K Ozer, H Oxman, M Lednicky, J Minor, P Morris, A Strickler, H Carbone, M Fisher, BL Frisque, R Kyle, W Procopio, A Garcea, R Martin, R Weiss, R Chen, R Villareal, L Klein, G Tevethia, S Imperiale, M Rattner, H O'Neill, F AF Shah, K Levine, A Butel, J Urnovitz, H Pass, H Goedert, J Dorries, K Ozer, H Oxman, M Lednicky, J Minor, P Morris, A Strickler, H Carbone, M Fisher, BL Frisque, R Kyle, W Procopio, A Garcea, R Martin, R Weiss, R Chen, R Villareal, L Klein, G Tevethia, S Imperiale, M Rattner, H O'Neill, F BE Brown, F Lewis, AM TI SV40 as a putative human commensal - Opening remarks - Panel-audience discussion II SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, Baltimore, MD 21205 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Chron Illness Res Found, San Francisco, CA 94121 USA. Wayne State Univ, Harper Hosp, Ctr Inst, Detroit, MI 48201 USA. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Univ Wuerzburg, Inst Virol, D-97078 Wuerzburg, Germany. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Calif San Diego, Med Ctr, Infect Dis Sect 111 F, San Diego, CA 92161 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Nat Vacc Informat Ctr, Vienna, VA 22180 USA. Penn State Univ, University Pk, PA 16802 USA. Amer Soc Microbiol, Hingham, MA 02043 USA. Univ G DAnnunzio, I-66013 Chieti, Italy. Univ Colorado, Dept Pediat, Denver, CO 80262 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. CDC, Atlanta, GA 30333 USA. Univ Calif Irvine, Irvine, CA 92697 USA. Karolinska Inst, S-17177 Stockholm, Sweden. Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Child & Family Quarterly, Oak Pk, IL 60303 USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. US FDA, CBER, Rockville, MD 20852 USA. RP Shah, K (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 251 EP 269 PG 19 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300030 ER PT S AU Pass, HI Mew, DJY Carbone, M Donington, JS AF Pass, HI Mew, DJY Carbone, M Donington, JS BE Brown, F Lewis, AM TI The effect of an antisense expression plasmid to the IGF-1 receptor on hamster mesothelioma proliferation SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM DE ICF; receptor; mesothelioma; hamster; antisense ID GROWTH-FACTOR-I; CELL-LINES; T-ANTIGEN; TRANSFORMATION; TUMORS AB We have evaluated the effect of antisense IGF receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor(IGF-1 R) genes was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells were electroporated with inducible expression Vectors (under the transcriptional control of heat shock promotor HSP70) containing a cDNA fragment corresponding to bp 1-309 of IGF-1R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (p(2) < 0.02). At 34 degrees C, cell growth of A3 sense and B9 antisense transfected cells was not significantly different. The A3 sense clones resulted in greater numbers of tumours in vivo compared to the B9 antisense clone (p(2) = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma. C1 NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. NCI, Biostat Sect, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Thomas Jefferson Univ, Jefferson Med Coll, Jefferson Canc Inst, Philadelphia, PA 19107 USA. RP Pass, HI (reprint author), Wayne State Univ, Harper Hosp, Karmanos Canc Inst, 3990 John R,Suite 2102, Detroit, MI 48201 USA. FU NCEH CDC HHS [NIEHS 06658]; NIGMS NIH HHS [GM-33694] NR 26 TC 9 Z9 9 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 321 EP 328 PG 8 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300037 PM 9776253 ER PT S AU Procopio, A Goedert, J Cook, J Carbone, M Urnowitz, H Weiss, R Ozer, H Pipas, J Strickler, H Pass, H Fried, M Shah, K Lednicky, J Butel, J Lewis, A Dorries, K Oxman, M Fisher, BL O'Neill, F Ross, M AF Procopio, A Goedert, J Cook, J Carbone, M Urnowitz, H Weiss, R Ozer, H Pipas, J Strickler, H Pass, H Fried, M Shah, K Lednicky, J Butel, J Lewis, A Dorries, K Oxman, M Fisher, BL O'Neill, F Ross, M BE Brown, F Lewis, AM TI SV as an oncogenic virus and possible human pathogen - Panel-audience discussion III SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 Univ G DAnnunzio, I-66013 Chieti, Italy. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Chron Illness Res Found, San Francisco, CA 94121 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Wayne State Univ, Harper Hosp, Ctr Inst, Detroit, MI 48201 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, Baltimore, MD 21205 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. US FDA, CBER, Rockville, MD 20852 USA. Univ Wuerzburg, Inst Virol, D-97078 Wuerzburg, Germany. Univ Calif San Diego, Med Ctr, Infect Dis Sect 111 F, San Diego, CA 92161 USA. Nat Vacc Informat Ctr, Vienna, VA 22180 USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. US Geol Survey, Reston, VA 22092 USA. RP Procopio, A (reprint author), Univ G DAnnunzio, Via Vestini 31, I-66013 Chieti, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 369 EP 382 PG 14 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300042 ER PT S AU Cushman, SW Goodyear, LJ Pilch, PF Ralston, E Galbo, H Ploug, T Kristiansen, S Klip, A AF Cushman, SW Goodyear, LJ Pilch, PF Ralston, E Galbo, H Ploug, T Kristiansen, S Klip, A BE Richter, EA Kiens, B Galbo, H Saltin, B TI Molecular mechanisms involved in GLUT4 translocation in muscle during insulin and contraction stimulation SO SKELETAL MUSCLE METABOLISM IN EXERCISE AND DIABETES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Copenhagen-Muscle-Research-Centre Symposium on Regulation of Skeletal Muscle Metabolism - Focus on Glucose Transport, Exercise, and Diabetes CY OCT 23-26, 1997 CL COPENHAGEN, DENMARK SP Copenhagen Muscle Res Ctr ID ACTIVATED PROTEIN-KINASE; RAT SKELETAL-MUSCLE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RESPONSIVE GLUCOSE-TRANSPORTER; 3T3-L1 ADIPOCYTES; MAP KINASE; MAJOR PROTEIN; ADIPOSE-CELLS; S6 KINASE; GLUT4-CONTAINING VESICLES AB Studies in mammalian cells have established the existence of numerous intracellular signaling cascades that are critical intermediates in the regulation of various biological functions. Over the past few years considerable research has shown that many of these signaling proteins are expressed in skeletal muscle. However, the detailed mechanisms involved in the regulation of glucose transporter (GLUT4) translocation from intracellular compartments to the cell surface membrane in response to insulin and contractions in skeletal muscle are not well understood. In the present essay we report three different approaches to unravel the GLUT4 translocation mechanism: 1. specific pertubation of the insulin and/or contraction signaling pathways; 2. characterization of the protein composition of GLUT4-containing vesicles with the expectation that knowledge of the constituent proteins of the vesicles may help in understanding their trafficking; 3. degree of co-immunolocalization of the GLUT4 glucose transporters with other membrane marker proteins assessed by immunofluorescense and electron microscopy. C1 NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD USA. RP Kristiansen, S (reprint author), Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, DK-2100 Copenhagen, Denmark. FU NIAMS NIH HHS [AR42238] NR 74 TC 31 Z9 31 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45920-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 441 BP 63 EP 71 PG 9 WC Endocrinology & Metabolism; Medicine, Research & Experimental; Nutrition & Dietetics; Physiology SC Endocrinology & Metabolism; Research & Experimental Medicine; Nutrition & Dietetics; Physiology GA BL64K UT WOS:000076155700006 PM 9781314 ER PT J AU Whitney, CW Enright, PL Newman, AB Bonekat, W Foley, D Quan, SF AF Whitney, CW Enright, PL Newman, AB Bonekat, W Foley, D Quan, SF TI Correlates of daytime sleepiness in 4578 elderly persons: The cardiovascular health study SO SLEEP LA English DT Article DE daytime somnolence; sleep disorders; elderly; magnetic resonance imaging ID OLDER ADULTS; CIGARETTE-SMOKING; SCALE; DISTURBANCE; COMMUNITY; APNEA; RISK; POPULATION; PREVALENCE; COMPLAINTS AB To describe the prevalence of self-reported daytime sleepiness in older men and women and to describe their relationships with demographic factors, nocturnal complaints, health status, and cardiovascular diseases (CVD). Design: Cross-sectional survey and clinical exam. Setting: Participants in the Cardiovascular Health Study, 4578 adults aged 65 and older, recruited from a random sample of non-institutionalized Medicare enrollees in four U.S, communities. Measures: Daytime sleepiness measured by the Epworth Sleepiness Scale (ESS), magnetic resonance imaging of the brain (MRI), cognitive function tests, and standardized questionnaires for cardiopulmonary symptoms and diseases, depressive symptoms, social support, activities of daily living, physical activity, and current medications. Results: Approximately 20% of the participants reported that they were "usually sleepy in the daytime." Although elderly black men were less likely to report frequent awakenings than those in the other three race and gender groups, they had significantly higher mean ESS scores. The following were independently associated with higher ESS scores in gender-specific models: non-white race, depression, loud snoring, awakening with dyspnea or snorting, frequent nocturnal awakenings, medications used to treat congestive heart failure, non-use of sleeping pills, a sedentary lifestyle, and limitation of activities of daily living in both men and women; additional correlates included hip circumference and current smoking in men, and hayfever in women. The following were not independently associated with ESS in the models: age, education, use of wine or beer to aid sleep, use of tricyclic antidepressants, long-or short-acting benzodiazepines, asthma, angina, myocardial infarction, congestive heart failure itself, forced vital capacity, social support, cognitive function, or MRI evidence of global brain atrophy or white matter abnormality. Conclusions: Daytime sleepiness is common in the elderly, probably due to nocturnal disturbances such as frequent awakenings and snoring. The occasional use of sleeping pills for insomnia is associated with reduced daytime sleepiness in the elderly, while the use of medications for congestive heart failure is associated with daytime sleepiness. Surprisingly, anatomic abnormalities such as evidence of previous strokes and brain atrophy (as seen on brain MRI scans) were not associated with daytime sleepiness in these non-institutionalized elderly persons. C1 Univ Arizona, Hlth Sci Ctr, Resp Sci Ctr, Tucson, AZ 85724 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Allegheny Gen Hosp, Med Coll Penn & Hahnemann Univ, Dept Med, Pittsburgh, PA 15212 USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. NIA, Bethesda, MD 20892 USA. RP Enright, PL (reprint author), Univ Arizona, Hlth Sci Ctr, Resp Sci Ctr, Rm 2342,1501 N Campbell Ave, Tucson, AZ 85724 USA. EM lungguy@aol.com RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 52 TC 172 Z9 181 U1 1 U2 13 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 USA SN 0161-8105 J9 SLEEP JI Sleep PY 1998 VL 21 IS 1 BP 27 EP 36 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YV738 UT WOS:000071857800004 PM 9485530 ER PT J AU Puck, TT Johnson, R Webb, P Yohrling, G AF Puck, TT Johnson, R Webb, P Yohrling, G TI Mutation measurement in mammalian cells IV: Comparison of gamma-ray and chemical mutagenesis SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID HUMAN-LYMPHOCYTES; CHROMOSOMAL-ABERRATIONS; ALKYLATING-AGENTS; X-RAYS; CAFFEINE; IRRADIATION; G2; CANCER; DNA; APOPTOSIS AB The interaction of chemical mutagens with mammalian cells is much more complex than that of gamma-irradiation because of the different ways in which chemical agents react with cell and medium components. Nevertheless, the system previously described for analysis of mutagenesis by gamma-radiation appears applicable to chemical mutagenesis. The approach involves measurement of cell survival, use of caffeine to inhibit repair; analysis of mitotic index changes, and quantitation of microscopically visible structural changes in mitotic chromosomes. The behavior of a variety of chemical mutagens and nonmutagens in this system is described and compared with that of gamma-irradiation. The procedure is simple and the results reasonably quantitative though less so than those of gamma-irradiation. The procedure can be used for environmental monitoring, analysis of mutational events, and individual and epidemiological testing, Mutational events should be classified as primary or secondary depending on whether they represent initial genomic insult, or genomic changes resulting from primary mutation followed by structural changes due to metabolic actions, While caffeine has multiple effects on the mammalian genome, when used under the conditions specified here it appears to act principally as an inhibitor of mutation repair and so affords a measure of the role of repair in the action of different mutagens on cells in the G2 phase of the life cycle. C1 Eleanor Roosevelt Inst, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Ctr Canc, Denver, CO 80262 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Puck, TT (reprint author), Eleanor Roosevelt Inst, 1899 Gaylord St, Denver, CO 80206 USA. FU PHS HHS [C206/60845] NR 32 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD JAN PY 1998 VL 24 IS 1 BP 1 EP 11 DI 10.1007/BF02677491 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 119CN UT WOS:000075877900001 PM 9776977 ER PT J AU Winter, DB Sattar, N Gearhart, PJ AF Winter, DB Sattar, N Gearhart, PJ TI The role of promoter-intron interactions in directing hypermutation SO SOMATIC DIVERSIFICATION OF IMMUNE RESPONSES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID SOMATIC HYPERMUTATION; GERMINAL CENTER; IMMUNOGLOBULIN GENES; AFFINITY MATURATION; VARIABLE GENES; T-CELLS; TRANSGENES; MUTATION; REGION; KAPPA C1 NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Natl Inst Transplantat, Los Angeles, CA 90057 USA. RP Winter, DB (reprint author), NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Box 01,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 32 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 229 BP 1 EP 10 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA BK18V UT WOS:000071447300001 PM 9479843 ER PT J AU Pospisil, R Mage, RG AF Pospisil, R Mage, RG TI Rabbit appendix: A site of development and selection of the B cell repertoire SO SOMATIC DIVERSIFICATION OF IMMUNE RESPONSES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID HUMORAL IMMUNE-SYSTEM; GENE CONVERSION; SIGNAL-TRANSDUCTION; POSITIVE SELECTION; ANTIBODY DIVERSITY; REGION SEQUENCES; ALICIA RABBITS; VH; DIVERSIFICATION; EXPRESSION C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Pospisil, R (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. RI Pospisil, Richard/B-7467-2012 NR 42 TC 31 Z9 32 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 229 BP 59 EP 70 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA BK18V UT WOS:000071447300006 PM 9479848 ER PT B AU Rumsey, JM Eden, G AF Rumsey, JM Eden, G BE Shapiro, BK Accardo, PJ Capute, AJ TI Functional neuroimaging of developmental dyslexia - Regional cerebral blood flow in dyslexic men SO SPECIFIC READING DISABILITY: A VIEW OF THE SPECTRUM LA English DT Proceedings Paper CT 19th Annual Spectrum of Developmental Disabilities Course CY MAR 18-20, 1996 CL JOHNS HOPKINS MED INST, BALTIMORE, MD HO JOHNS HOPKINS MED INST C1 NIMH, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU YORK PRESS PI PARKTON PA 2712 MT CARMEL RD, PARKTON, MD 21120 USA BN 0-912752-45-9 PY 1998 BP 35 EP 62 PG 28 WC Education, Special; Psychology, Educational; Psychology, Developmental; Psychiatry; Psychology, Experimental SC Education & Educational Research; Psychology; Psychiatry GA BK67R UT WOS:000073040500003 ER PT J AU Tosato, G Teruya-Feldstein, J Setsuda, J Pike, SE Jones, KD Jaffe, ES AF Tosato, G Teruya-Feldstein, J Setsuda, J Pike, SE Jones, KD Jaffe, ES TI Post-transplant lymphoproliferative disease (PTLD): lymphokine production and PTLD SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; B-CELL LINES; TUMOR-NECROSIS-FACTOR; AUTOCRINE GROWTH-FACTOR; NF-KAPPA-B; HUMAN LYMPHOCYTES-B; INTERFERON-INDUCIBLE PROTEIN-10; INTERLEUKIN-1 (IL-1)-LIKE FACTOR; LATENT MEMBRANE-PROTEIN; INFECTIOUS-MONONUCLEOSIS C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, NIH Campus,Bldg 29A,Room 2D06,1401 Rockville Pike, Bethesda, MD 20892 USA. NR 175 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1998 VL 20 IS 3-4 BP 405 EP 423 DI 10.1007/s002810050044 PG 19 WC Immunology; Pathology SC Immunology; Pathology GA 147NC UT WOS:000077572700007 PM 9870254 ER PT J AU Candotti, F O'Shea, JJ Villa, A AF Candotti, F O'Shea, JJ Villa, A TI Severe combined immune deficiencies due to defects of the common gamma chain-JAK3 signaling pathway SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; LINKED COMBINED IMMUNODEFICIENCY; HEMATOPOIETIC PROGENITOR CELLS; IN-UTERO TRANSPLANTATION; MICE LACKING JAK3; IL-2 RECEPTOR; LYMPHOID DEVELOPMENT; BONE-MARROW; INTERLEUKIN-2 IL-2; T-CELLS C1 Univ Brescia, Dept Pediat, Spedali Civili, I-25123 Brescia, Italy. NIAMS, Lymphocyte Cell Biol Sect, ARB, NIH, Bethesda, MD USA. Natl Res Council, Inst Adv Biotechnol, Milan, Italy. RP Candotti, F (reprint author), Univ Brescia, Dept Pediat, Spedali Civili, I-25123 Brescia, Italy. OI Villa, Anna/0000-0003-4428-9013 NR 83 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1998 VL 19 IS 4 BP 401 EP 415 DI 10.1007/BF00792599 PG 15 WC Immunology; Pathology SC Immunology; Pathology GA ZP003 UT WOS:000073705600004 PM 9618765 ER PT J AU Candotti, F Blaese, RM AF Candotti, F Blaese, RM TI Gene therapy of primary immunodeficiencies SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; LEUKOCYTE ADHESION DEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; CLASS-II DEFICIENCY; BONE-MARROW CELLS; DEFECTIVE LYMPHOID DEVELOPMENT; PERIPHERAL-BLOOD LYMPHOCYTES; X-LINKED AGAMMAGLOBULINEMIA C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Univ Brescia, Dept Pediat, Brescia, Italy. RP Blaese, RM (reprint author), Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1998 VL 19 IS 4 BP 493 EP 508 DI 10.1007/BF00792604 PG 16 WC Immunology; Pathology SC Immunology; Pathology GA ZP003 UT WOS:000073705600009 PM 9618770 ER PT J AU Tian, ZG Woody, MA Sun, R Welniak, LA Raziuddin, A Funakoshi, S Tsarfaty, G Longo, DL Murphy, WJ AF Tian, ZG Woody, MA Sun, R Welniak, LA Raziuddin, A Funakoshi, S Tsarfaty, G Longo, DL Murphy, WJ TI Recombinant human growth hormone promotes hematopoietic reconstitution after syngeneic bone marrow transplantation in mice SO STEM CELLS LA English DT Article DE growth hormone; neuroendocrine; hematopoiesis; bone marrow transplantation ID SOMATOMEDIN-C; INTERLEUKIN-6; RECOVERY; INVIVO AB Recombinant human growth hormone (rhGH) was administered to mice after syngeneic bone marrow transplantation (BMT) to determine its effect on hematopoietic reconstitution. BALB/c mice were given 10 mu g intraperitoneal injections of rhGH every other day for a total of 10 injections following syngeneic BMT, Mice that received rhGH exhibited significant increases in total hematopoietic progenitor cell content (colony-forming unit-culture) in both bone marrow and spleen. Erythroid cell progenitor content (burst-forming unit-erythroid) was also significantly increased after rhGH treatment. Analysis of peripheral blood indicated that administration of rhGH resulted in significant increases in the rate of white blood cell and platelet recovery. Granulocyte marker 8C5(+) cells were also increased in the bone marrow and spleens of treated mice. Red blood cell, hematocrit, and hemoglobin levels were increased at all time points after rhGH treatment. No significant pathologic effects or weight gain were observed in mice receiving repeated injections of 10 mu g rhGH. Thus, rhGH administration after syngeneic BMT promoted multilineage hematopoietic reconstitution and may be of clinical use for accelerating hematopoiesis after autologous BMT. C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Frederick, MD 21702 USA. NIA, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Bldg 567,Room 210, Frederick, MD 21702 USA. RI Tian, Zhigang/J-3512-2013 NR 19 TC 50 Z9 53 U1 0 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 1998 VL 16 IS 3 BP 193 EP 199 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA ZN176 UT WOS:000073617500004 PM 9617894 ER PT J AU Rao, PN Cessac, JW Blye, RP Kim, HK AF Rao, PN Cessac, JW Blye, RP Kim, HK TI 11 beta-substituted 13 beta-ethyl gonane derivatives exhibit reversal of antiprogestational activity SO STEROIDS LA English DT Article DE synthesis; 13 beta-ethyl gonane derivatives; CDB-2914; progestin; antiprogestin ID PROGESTIN RECEPTORS; ANTAGONIST; STEROIDS; BINDING; COMFA AB The syntheses of three 17 alpha-acetoxy-13 beta-ethyl-11 beta-aryl-18,19-dinorpregna-4,9-diene-3,20 diones from levonorgestrel are described Despite their close structural similarity To the antiprogesterone CDB-2914, one of the compounds exhibits agonistic progestational activity, and the other two compounds are totally inactive. (C) 1998 by Elsevier Science Inc. C1 SW Fdn Biomed Res, Dept Organ Chem, San Antonio, TX 78245 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Rao, PN (reprint author), SW Fdn Biomed Res, Dept Organ Chem, POB 760549, San Antonio, TX 78245 USA. FU NICHD NIH HHS [N01-HD-1-3137] NR 27 TC 6 Z9 6 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD JAN PY 1998 VL 63 IS 1 BP 50 EP 57 DI 10.1016/S0039-128X(97)00119-0 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA YP724 UT WOS:000071308100008 PM 9437795 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR BE Yeung, MM Yeo, BL Bouman, CA TI Image query and indexing for digital x-rays SO STORAGE AND RETRIEVAL FOR IMAGE AND VIDEO DATABASES VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 7th Storage and Retrieval for Image and Video Databases Conference CY JAN 26-29, 1999 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers DE World Wide Web; biomedical; informatics; Internet; database; spine; digital image; morphometry; x-ray image; image query by content; NHANES; NLM; NCHS; NIAMS AB The Web-based Medical Information Retrieval System (WebMIRS) allows Internet access to databases containing 17,000 digitized x-ray spine images and associated text data from National Health and Nutrition Examination Surveys (NHANES). WebMIRS allows SQL query of the text, and viewing of the returned test records and images using a standard browser. We are now working (1) to determine utility of data directly derived from the images in our databases and (2) to investigate the feasibility of computer-assisted or automated indexing of the images to support image retrieval of images of interest to biomedical researchers in the field of osteoarthritis. To build an initial database based on image data, we are manually segmenting a subset of the vertebrae, using techniques from vertebral morphometry. From this, we will derive and add to the database vertebral features. This image-derived data will enhance the user's data access capability by enabling the creation of combined SQL/image-content queries. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3127-3 J9 P SOC PHOTO-OPT INS PY 1998 VL 3656 BP 12 EP 21 DI 10.1117/12.333839 PG 10 WC Computer Science, Software Engineering; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BM50P UT WOS:000078907700002 ER PT S AU Chrousos, GP AF Chrousos, GP BE Csermely, P TI Stressors, stress, and neuroendocrine integration of the adaptive response - The 1997 Hans Selye Memorial Lecture SO STRESS OF LIFE: FROM MOLECULES TO MAN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Stress of Life - Stress and Adaptation from Molecules to Man CY JUL 01-05, 1997 CL BUDAPEST, HUNGARY SP Hungarian Minist Environm Protect, Malev Hungarian Airlines, Hans Selye Fdn, Canada, Hungarian Natl Comm Technol Dev, Decade Brain Res Fdn, Hungarian Soc Expt & Clin Pharm, European Mol Biol Org, Biorex Co, Hungary, Operator Ltd, Hungary, Babolna Co, Hungarian Immunol Fdn, Assoc Cape Cod Inc, Kevi Farkas Ltd, Molnar Ltd, Hungarian Sci Res Fdn, Dicso Trapp Ltd, Vagabund Ltd ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; BIOCHEMICAL MANIFESTATIONS; CLINICAL IMPLICATIONS; SECRETION INVITRO; CUSHINGS-SYNDROME; MAJOR DEPRESSION; GENE-EXPRESSION; HYPERCORTISOLISM; INFLAMMATION C1 NIH, Pediat Endocrinol Sect, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Pediat Endocrinol Training Program, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NIH, Pediat Endocrinol Sect, Dev Endocrinol Branch, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 53 TC 385 Z9 401 U1 4 U2 38 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-116-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 851 BP 311 EP 335 DI 10.1111/j.1749-6632.1998.tb09006.x PG 25 WC Multidisciplinary Sciences; Neurosciences; Physiology SC Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BL26K UT WOS:000074934900039 PM 9668623 ER PT J AU Alkayed, NJ Harukuni, I Kimes, AS London, ED Traystman, RJ Hurn, PD AF Alkayed, NJ Harukuni, I Kimes, AS London, ED Traystman, RJ Hurn, PD TI Gender-linked brain injury in experimental stroke SO STROKE LA English DT Article DE cerebral blood flow; estrogens; stroke, experimental; gender; neuroprotection ID CEREBRAL BLOOD-FLOW; ESTROGEN-RECEPTORS; HORMONE REGULATION; ENDOTHELIAL-CELLS; ARTERY OCCLUSION; FOCAL ISCHEMIA; VESSEL WALL; RATS; DISEASE; WOMEN AB Background and Purpose-Premenopausal women are at lower risk than men for stroke, but the comparative vulnerability to tissue injury once a cerebrovascular incident occurs is unknown, We hypothesized that female rats sustain less brain damage than males during experimental focal ischemia and that the gender difference in ischemic outcome can be eliminated by ovariectomy, Methods-Age-matched male (M), intact female (F), and ovariectomized female (O; plasma estradiol: 4.1 +/- 1.6 pg/mL compared with 7.4 +/- 1.5 in F and 4.0 +/- 1.1 in M) rats from two different strains, normotensive Wistar and stroke-prone spontaneously hypertensive rats, were subjected to 2 hours of intraluminal middle cerebral artery occlusion, followed by 22 hours of reperfusion. Cerebral blood flow (CBF) was monitored throughout the ischemic period by laser-Doppler flowmetry. Infarction volume in the cerebral cortex (Cts) and caudoputamen (CP) was determined by 2,3,5-triphenyl-tetrazolium chloride staining. In a separate cohort of M, F, and O Wistar rats, absolute rates of regional CBF were measured at the end of the ischemic period by quantitative autoradiography using [C-14]iodoantipyrine. Results-F rats of either strain had a smaller infarct size in Ctx and CP and a higher laser-Doppler flow during ischemia compared with respective M and O rats. Mean end-ischemic CBF was higher-in F compared with M and O rats in CP, but not in Ctx. Cerebrocortical tissue volume with end-ischemic CBF <10 mL/100 g/min was smaller in F than M rats, but nor different from O rats. Conclusions-We conclude that endogenous estrogen improves stroke outcome during vascular occlusion by exerting both neuroprotective and flow-preserving effects. C1 Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. NIDA, Baltimore, MD USA. RP Hurn, PD (reprint author), Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, 600 N Wolfe St,Blalock 1404, Baltimore, MD 21287 USA. EM phurn@welchlink.welch.jhu.edu FU NINDS NIH HHS [NS20020, NS3368] NR 41 TC 484 Z9 498 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 BP 159 EP 165 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100030 PM 9445346 ER PT J AU Grady, PA AF Grady, PA TI Gender-linked brain injury in experimental stroke - Comment SO STROKE LA English DT Editorial Material C1 Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 BP 166 EP 166 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100031 ER PT J AU Dawson, DA Hallenbeck, JM Spatz, M AF Dawson, DA Hallenbeck, JM Spatz, M TI The endothelin antagonist RO61-1790 attenuates focal cerebral ischemic injury SO STROKE LA English DT Meeting Abstract C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 MA P124 BP 323 EP 323 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100265 ER PT J AU Frerichs, KU Hallenbeck, JM AF Frerichs, KU Hallenbeck, JM TI Mammalian hibernation induces state and species-specific tolerance to hypoxia and a glycemia in hippocampal slices SO STROKE LA English DT Meeting Abstract C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Div Neurosurg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 MA P144 BP 326 EP 326 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100285 ER PT J AU Ginis, I Neuhaus, IM Spatz, M Hallenbeck, JM AF Ginis, I Neuhaus, IM Spatz, M Hallenbeck, JM TI TNF alpha treated astrocytes protect neutrophils against hypoxia-induced motility SO STROKE LA English DT Meeting Abstract C1 NINDS, Stroke Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 MA P143 BP 326 EP 326 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100284 ER PT J AU Becker, KJ McCarron, RM Hallenbeck, JM AF Becker, KJ McCarron, RM Hallenbeck, JM TI Magnitude of fever predicts outcome after transient middle cerebral artery occlusion SO STROKE LA English DT Meeting Abstract C1 NIH, Stroke Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1998 VL 29 IS 1 MA P153 BP 328 EP 328 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YQ726 UT WOS:000071417100294 ER PT S AU Marler, JR Fieschi, C Higashida, R Boysen, G AF Marler, JR Fieschi, C Higashida, R Boysen, G BE Steiner, T Hacke, W Hanley, DF TI Thrombolytic therapy in acute ischemic stroke SO STROKE: EMERGENCY MANAGEMENT AND CRITICAL CARE SE UPDATE IN INTENSIVE CARE AND EMERGENCY MEDICINE LA English DT Proceedings Paper CT 1st Conference on Emergency Management and Critical Care of Stroke CY SEP, 1996 CL UNIV HEIDELBERG, HEIDELBERG, GERMANY HO UNIV HEIDELBERG C1 NINDS, Div Stroke & Trauma, Bethesda, MD 20892 USA. RP Marler, JR (reprint author), NINDS, Div Stroke & Trauma, Fed Bldg,Room 800,7550 Wisconsin Ave, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-6788 BN 3-540-61880-5 J9 UPD INT CAR PY 1998 VL 27 BP 75 EP 83 PG 9 WC Emergency Medicine SC Emergency Medicine GA BL18S UT WOS:000074632300008 ER PT B AU Cheatham, TE Kollman, PA AF Cheatham, TE Kollman, PA BE Sarma, RH Sarma, MH TI Molecular dynamics simulation of nucleic acids in solution: How sensitive are the results to small perturbations in the force field and environment? SO STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 1 LA English DT Proceedings Paper CT 10th Conversation in Biomolecular Stereodynamics Conference CY JUN 17-21, 1997 CL SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM, ALBANY, NY SP US NIH HO SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM AB A series of simulations of the DNA duplex d[CCAACGTTGG](2) in solution are described. In each case, the Cornell et al, nucleic acid force field is applied with a particle mesh Ewald treatment where subtle perturbations to the protocol, parameters or environment have been performed in order to test the sensitivity of the model. Except in cases where the sugar puckers are constrained or changes in torsional parameters which effect the sugar pucker equilibrium are made, the structures obtained are profoundly insensitive to the perturbations (as exemplified by simulations with reduced phosphate charges, no net-neutralizing salt, addition of 50 additional Na+ and Cl- ions leading to a salt concentration of 1M, modified water models, reduced pressure or modified base stacking interactions). Even in cases where fairly large perturbations are made, such as when the charges on the TIP3P water model are reduced by 10% which leads to water diffusion roughly five times what is expected experimentally, equivalent nanosecond average structures to those seen in simulations with the standard TIP3P or SPC/E water models are seen. Shifting the distribution of sugar puckers towards C3'-endo is shown to reduce the helical twist and generally shift the structure to be closer to A-DNA; however, a complete transition from B-DNA to A-DNA is not seen even when the pucker is constrained to C3'-endo. These observations suggest that improvements to the simulation protocol and parameters will likely have to come from a series of small and additive corrections. Despite the apparent insensitivity of the B-DNA model on a nanosecond time scale to small perturbations (which suggests the need for longer simulations), recent simulations suggest that these models can properly represent some effect of the environment in 1-10 nanosecond length simulations. C1 NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Kollman, PA (reprint author), NIH, Struct Biol Lab, Div Comp Res & Technol, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 20 Z9 22 U1 0 U2 1 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA BN 0-940030-76-4 PY 1998 BP 99 EP 116 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BL51F UT WOS:000075702000009 ER PT B AU Htun, H Walker, D Hager, GL AF Htun, H Walker, D Hager, GL BE Sarma, RH Sarma, MH TI Optical imaging approach to study protein-DNA interaction and nuclear organization in cultured living cells SO STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 1 LA English DT Proceedings Paper CT 10th Conversation in Biomolecular Stereodynamics Conference CY JUN 17-21, 1997 CL SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM, ALBANY, NY SP US NIH HO SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM AB Subcellular trafficking and localization of the glucocorticoid receptor (GR) has been followed with the green fluorescent protein (GFP)-GR chimeric protein. When expressed in mammalian tissue culture cells, GFP is present throughout the cellular Volume but is excluded from some vesicles in the cytoplasm and nucleoli in the nucleus. When fused to GR, green fluorescence becomes restricted to the cytoplasm and concentrates along fibrillar structures with no green fluorescence detected in the nucleus. Treatment with ligand leads to translocation to the nucleus with agonist ligand, such as dexamethasone, inducing accumulation of GFP-GR chimeric protein into nuclear foci. Accumulation into foci, in part, reflects targeting of GFP-GR to target genes, since the introduction of exogenous GR-binding sites leads to new patterns of accumulation. In the case of a cell line containing a large tandem array of the mouse mammary tumor virus long terminal repeat (MMTV LTR), the foci are not reserved leading to the appearance of a ribbon-like structure upon accumulation of GFP-GR on the GR-binding sites in the MMTV LTR tandem array. Mutational analysis of the GR DNA-binding domain reveals the importance of this domain for both the accumulation into nuclear foci as well as targeting to the GR-binding sites in the large tandem array. The use of GFP chimeric proteins and large tandem array of a define DNA sequence provides a unique opportunity to study DNA-protein interaction and the organization of the interphase nucleus in live cells. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Htun, H (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 14,Room B517,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA BN 0-940030-76-4 PY 1998 BP 157 EP 165 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BL51F UT WOS:000075702000014 ER PT B AU Norel, R Lin, SL Xu, D Wolfson, HJ Nussinov, R AF Norel, R Lin, SL Xu, D Wolfson, HJ Nussinov, R BE Sarma, RH Sarma, MH TI Molecular surface variability and induced conformational changes upon protein-protein association SO STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 2 LA English DT Proceedings Paper CT 10th Conversation in Biomolecular Stereodynamics Conference CY JUN 17-21, 1997 CL SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM, ALBANY, NY SP US NIH HO SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM AB Most docking approaches strive to obtain low root-mean-squared deviations in the predicted as compared to the observed, crystal docked configurations. However, in reality, even for the so-called rigid-body docking case, surface variability unquestionably occurs. Comparison of the crystal-bound versus crystal uncomplexed molecules suffices to gauge the extent of such a variability Furthermore, upon molecular binding, induced shifts of surface atoms, optimizing molecular interactions takes place. This work specifically addresses variability, and flexibility, of surface atoms in solution and upon binding. To investigate this, 'real-life' problem, we examine the displacements of atoms on the surfaces of proteins with respect to those observed in their interior. In particular, we analyze the patterns of displacements of atoms which are exposed to the solvent, and those which are on the surface in the uncomplexed protein molecules, and become buried in the interface upon complex formation. These studies, of the induced atomic shifts upon protein-protein associations, are carried out by comparisons of pairs of similar structures which have been crystallized both in the complexed and in the uncomplexed states. Such a study provides a range of the variability of surface atoms and of the induced conformational shifts of the surface atoms upon molecular interactions, useful for more realistic docking simulations. Here we present the results obtained in extensive protein-protein docking calculations using the obtained ranges. 26 bound cases, where the molecules have been crystallized when in a complexed form, and 19 unbound cases have been docked. The docked conformations have been clustered using liberal thresholds, in consideration of the range of surface variability we have observed. The RMSD's obtained are satisfactory, (with the RMS deviations between 0.5 Angstrom to 2.5 Angstrom, and between 1.2 Angstrom to 5.2 Angstrom for the bound and for the unbound cases, respectively) and the matching times (at most 48 CPU min on a PC) are acceptable. Clustering reduces the number of solutions, and improves considerably the ranking of the 'correct' ones. We further focus on the case of one family, the trypsins and their inhibitors, applying it specifically to their active site regions. As expected, appreciable additional improvement is obtained. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Math Biol Lab, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Frederick, MD 21702 USA. Tel Aviv Univ, Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Math Biol Lab, Bldg 469,Rm 151, Frederick, MD 21702 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA BN 0-940030-77-2 PY 1998 BP 33 EP 51 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BL51G UT WOS:000075727100002 ER PT B AU Nagaich, AK Balagurumoorthy, P Miller, WM Appella, E Zhurkin, VB Harrington, RE AF Nagaich, AK Balagurumoorthy, P Miller, WM Appella, E Zhurkin, VB Harrington, RE BE Sarma, RH Sarma, MH TI Interactions between the p53 DNA binding domain and the p21/Waf1/Cip1 DNA response element SO STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 2 LA English DT Proceedings Paper CT 10th Conversation in Biomolecular Stereodynamics Conference CY JUN 17-21, 1997 CL SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM, ALBANY, NY SP US NIH HO SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM AB A cocrystal structure of a minimal core p53 DNA binding domain peptide (p53DBD) complexed with a DNA response element has provided much useful information on the binding specificity of p53 by identifying specific protein-DNA contacts. However, many unanswered questions remain including the full size and conformation of the complex and the organization and orientation of p53 tetramers bound to the subcomponents of the DNA recognition site. To further understand the binding behavior of p53 with its response elements, we have studied complexes between the p53DBD peptide (amino acids 98-309) and the p21/Waf1/Cip1 binding site. These include cyclization studies, binding affinity and stoichiometry assays using ultracentrifugation, and high resolution chemical probes footprinting. The studies demonstrate that the p53DBD peptide binds this response element as a tetrapeptide and induces DNA bending. The biochemical methods footprint the peptides on the DNA and identify protein-DNA contacts at single nucleotide resolution. Chemical probes studies on the p53 recognition sequence used in the cocrystal structure verify the protein-DNA contacts observed in the cocrystal, but also suggest additional ones that evidently correspond to a second binding site in this sequence. Although the p53DBD peptide associates negligibly in free solution, the present studies show that the p53DBD peptides form a self-directed tetrapeptide complex with the p21/Waf1/Cip1 response element and provide the first direct experimental evidence that the four subunits bind to the major groove on the same face of the response element DNA. They also show that the most important contacts are between each monomeric peptide and the invariant guanosine nucleotides in the highly conserved C(A/T)\(T/A)G part of the consensus half sites. C1 Univ Nevada, Sch Med, Dept Biochem 330, Reno, NV 89557 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Harrington, RE (reprint author), Univ Nevada, Sch Med, Dept Biochem 330, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA BN 0-940030-77-2 PY 1998 BP 249 EP 274 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BL51G UT WOS:000075727100022 ER PT B AU Durell, SR Jernigan, RL Appella, E Nagaich, AK Harrington, RE Zhurkin, VB AF Durell, SR Jernigan, RL Appella, E Nagaich, AK Harrington, RE Zhurkin, VB BE Sarma, RH Sarma, MH TI DNA bending induced by tetrameric binding of the p53 tumor suppressor protein: Steric constraints on conformation SO STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 2 LA English DT Proceedings Paper CT 10th Conversation in Biomolecular Stereodynamics Conference CY JUN 17-21, 1997 CL SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM, ALBANY, NY SP US NIH HO SUNY ALBANY, DEPT CHEM, INST BIOMOLEC STEREODYNAM AB The p53 tumor suppressor protein binds cooperatively to the DNA response elements in solution as a tetramer, with the DNA assuming a bent conformation. This is in contrast to the approximately "straight" conformation of DNA observed in a co-crystal complex, where only one of the three p53 DNA binding domains (p53DBD) present in the asymmetric unit is specifically bound. To investigate the restraints imposed by the protein tetramer, we have developed a systematic computer procedure to exhaustively sample the relative orientations accessible to four bound p53DBD subunits. This involved the use of symmetry and a generalized set of coordinate parameters to reduce the degrees of freedom. Characterization of the allowed and restricted conformational space was based on energy calculations, DNA sequence-dependent "conformational mechanics" and high resolution footprinting of the tetrameric p53DBD-DNA complex in solution. Using the co-crystal monomeric p53DBD-DNA complex as a starting structure, it is found that steric clashes between both the parallel and antiparallel pairs of protein subunits in the tetramer prevent the DNA from assuming a straight B-like conformation. Rather, specific bent conformations of the DNA sufficiently separate the protein subunits to alleviate the clashes and form stabilized complexes (likely contributing to the observed cooperativity of multimeric p53 binding to DNA). A subset of these conformations is consistent with the known bending anisotropy and extreme flexibility of the CATG tetramer at the pentamer junctions in most of the p53 binding sites (including the intensively studied p21/waf1/cip1 promoter involved in cell-cycle regulation). 3D structural modeling provides additional insights into the spatial interrelationships between the protein and the DNA conformations in the full tetrameric complex. Within the constraints imposed by the protein subunits, the DNA can assume a range of conformations resulting from correlated changes of the bend, twist and slide at the pentamer junctions of the response elements. This explains the asymmetric interactions of the highly conserved Arg248 residues with only one strand in the DNA minor groove observed in the solution state, which differs from the symmetric two-strand interactions in the crystal structure. Based on these results, we describe how p53 might bind to DNA response elements packaged in nucleosomes. Furthermore, our modeling shows that upon tetrameric binding of p53 to bent DNA, a novel positively and negatively charged site is formed on the "external" interface of the p53DBD subunits. This may serve as a binding site for the proteins involved in regulation of the cell-cycle control genes. C1 NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Nevada, Sch Med, Dept Biochem 330, Reno, NV 89557 USA. RP Zhurkin, VB (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 0 TC 4 Z9 4 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA BN 0-940030-77-2 PY 1998 BP 277 EP 295 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BL51G UT WOS:000075727100023 ER PT J AU Harrison, LD Backenheimer, M AF Harrison, LD Backenheimer, M TI Editors' introduction: Evolving insights into the drug-crime nexus SO SUBSTANCE USE & MISUSE LA English DT Editorial Material C1 Univ Delaware, Ctr Drug & Alcohol Studies, Newark, DE 19711 USA. NIDA, Off Extramural Program Review, NIH, Bethesda, MD USA. RP Harrison, LD (reprint author), Univ Delaware, Ctr Drug & Alcohol Studies, Newark, DE 19711 USA. NR 46 TC 12 Z9 12 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1998 VL 33 IS 9 BP 1763 EP 1777 DI 10.3109/10826089809059321 PG 15 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 109EK UT WOS:000075308100001 PM 9718179 ER PT J AU Robertson, E Donnermeyer, JF AF Robertson, E Donnermeyer, JF TI Patterns of drug use among nonmetropolitan and rural adults SO SUBSTANCE USE & MISUSE LA English DT Article DE illegal drug use; adults; rural; nonmetropolitan ID PEER CLUSTER THEORY; SUBSTANCE-ABUSE; ADOLESCENT; ALCOHOL AB This article examines illegal drug use among adults living in nonmetropolitan and rural areas of the United States using data from the National Household Survey on Drug Abuse. Subjects were classified into three categories by residence: nonmetropolitan-urban, metropolitan-rural, and nonmetropolitan-rural. Respondents indicate about 10% of adults were current users of marijuana or other illegal drugs. Discriminant analysis was used to examine differences among groups of individuals classified as current users, past users, and nonusers. For both marijuana and other illegal drugs, the variables that accounted most for group differences were age, marital, status, employment status, occupation, and income. Only minor differences in drug use were exhibited across the three residential categories. It is recommended that future research on the rural and nonmetropolitan adult population incorporate both structural level measures of socioeconomic and demographic characteristics of localities, and individual level measures of peer influence, work stress, family factors, and psychosocial characteristics. C1 NIDA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. Ohio State Univ, Coll Food Agr & Environm Sci, Dept Human & Community Dev, Columbus, OH 43210 USA. RP Robertson, E (reprint author), NIDA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. NR 34 TC 8 Z9 8 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1998 VL 33 IS 10 BP 2109 EP 2129 DI 10.3109/10826089809069818 PG 21 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 117YG UT WOS:000075810000004 PM 9744844 ER PT J AU Leshner, AI AF Leshner, AI TI Comments on "the moral economies of homeless heroin addicts: Confronting ethnography, HIV risk, and everyday violence in San Francisco shooting encampments," by Phillippe Bourgois SO SUBSTANCE USE & MISUSE LA English DT Editorial Material ID INFECTION C1 NIDA, Rockville, MD 20857 USA. RP Leshner, AI (reprint author), NIDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1998 VL 33 IS 11 BP 2369 EP 2374 DI 10.3109/10826089809056265 PG 6 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 124FQ UT WOS:000076172100011 PM 9758021 ER PT J AU Needle, RH Coyle, S Cesari, H Trotter, R Clatts, M Koester, S Price, L McLellan, E Finlinson, A Bluthenthal, RN Pierce, T Johnson, J Jones, TS Williams, M AF Needle, RH Coyle, S Cesari, H Trotter, R Clatts, M Koester, S Price, L McLellan, E Finlinson, A Bluthenthal, RN Pierce, T Johnson, J Jones, TS Williams, M TI HIV risk behaviors associated with the injection process: Multiperson use of drug injection equipment and paraphernalia in injection drug user networks SO SUBSTANCE USE & MISUSE LA English DT Article DE HIV/AIDS; injection drug users; drug sharing; ethnography; injections networks ID NEEDLE EXCHANGE; AIDS-PREVENTION; INFECTION; SYRINGE; TRANSMISSION; PREVALENCE AB This study examines drug acquisition and multiperson use of paraphernalia, drugs, and needles/syringes. Ethnographers observed 54 injection episodes in which IDUs were linked by HIV risk behaviors, and developed a typology of higher-risk, lower-risk, and nonsharing-risk networks. Multiperson use of injection paraphernalia or drug solution occurred in most injection events (94%). Serial use of syringes/needles occurred infrequently (14%) relative to "backloading" (37%) and reuse of paraphernalia (cookers 84%, cotton 77%, water 77%). Higher-risk injection networks were characterized by larger size and pooling of resources for drugs. Prevention messages must include avoiding reuse of injection paraphernalia and transfer of drug solution. C1 NIDA, Community Res Branch, Dept Epidemiol & Prevent Res, Rockville, MD 20857 USA. No Arizona Univ, Flagstaff, AZ 86011 USA. Natl Dev & Res Inst, New York, NY USA. Univ Colorado, Denver, CO 80202 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mental Hlth & Mental Retardat Author, Harris Cty, TX USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Needle, RH (reprint author), NIDA, Community Res Branch, Dept Epidemiol & Prevent Res, 5600 Fishers Lane,Room 9A-42, Rockville, MD 20857 USA. EM rh28e@nih.gov RI McLellan-Lemal, Eleanor/J-9720-2012; OI Bluthenthal, Ricky/0000-0003-3491-1702; McLellan-Lemal, Eleanor/0000-0002-1884-9315 FU PHS HHS [271-90-8400] NR 51 TC 55 Z9 56 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1998 VL 33 IS 12 BP 2403 EP 2423 DI 10.3109/10826089809059332 PG 21 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 126FP UT WOS:000076282600002 PM 9781822 ER PT J AU Abbott, LJ AF Abbott, LJ TI The use of alcohol by lesbians: A review and research agenda SO SUBSTANCE USE & MISUSE LA English DT Review DE lesbian alcohol; "moderate drinkers"; "heavy drinkers" ID BREAST-CANCER; HETEROSEXUAL WOMEN; UNITED-STATES; DRUG-USE; CONSUMPTION; PREVALENCE; POPULATION; CIRRHOSIS; ABUSE; MEN AB This article reviews the literature on alcohol use by lesbians. Comparisons of data on lesbians and women from the general population show that lesbians tend to drink more than other women; that rates of drinking do not decline with age as is true for general population women; and that even when levels of drinking are equivalent between lesbians and general population women, lesbians report greater difficulties related to alcohol consumption. Differences in sampling techniques and differences in definitions of drinking among the papers made comparisons of results difficult. These issues are discussed and recommendations are made concerning standardization of data collection. C1 NIAAA, Bethesda, MD 20892 USA. RP Abbott, LJ (reprint author), NIAAA, 6000 Execut Blvd, Bethesda, MD 20892 USA. NR 39 TC 11 Z9 11 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1998 VL 33 IS 13 BP 2647 EP 2663 DI 10.3109/10826089809059343 PG 17 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 132RX UT WOS:000076644800004 PM 9818992 ER PT J AU Mayo, DJ AF Mayo, DJ TI Fibrin sheath formation and chemotherapy extravasation: a case report SO SUPPORTIVE CARE IN CANCER LA English DT Article; Proceedings Paper CT 9th International Symposium on Supportive Care in Cancer CY FEB 26-MAR 01, 1997 CL ST GALLEN, SWITZERLAND DE extravasation; fibrin sheath; persistent withdrawal occlusion; venous access device; urokinase ID CENTRAL VENOUS CATHETERS; THROMBOSIS; MANAGEMENT; ACCESS; COMPLICATIONS AB Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). PWO is a common problem encountered with VADs, Although PWO is often easily managed with small doses of thrombolytic therapy (e.g., urokinase), it could result in a more serious complication, such as chemotherapy extravasation. Careful assessment of all VADs is important to identify complications such as fibrin sheath formation, which can potentially lead to extravasation. To rule out fibrin sheath formation, catheter dye studies need to be obtained when fibrinolytic therapy has failed to restore catheter function. The purpose of this paper is to illustrate a retrospective case report demonstrating drug extravasation caused by the development of fibrin sheath formation. C1 NIH, Bethesda, MD 20892 USA. RP Mayo, DJ (reprint author), NIH, Bldg 10,Room 2C-390,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 7 Z9 9 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JAN PY 1998 VL 6 IS 1 BP 51 EP 56 PG 6 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA ZT651 UT WOS:000074109200010 PM 9458537 ER PT J AU Zhao, H Burke, TR AF Zhao, H Burke, TR TI Facile syntheses of (2R,3R)-(-)- and (2S,3S)-(+)-chicoric acids SO SYNTHETIC COMMUNICATIONS LA English DT Article ID INHIBITORS; INTEGRASE AB Practical and efficient syntheses of (2R, 3R)-(-)- and (2S, 3S)-(+)-chicoric acids are reported, which may be amenable to analogue preparation. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 5 TC 13 Z9 16 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 1998 VL 28 IS 4 BP 737 EP 740 DI 10.1080/00397919808005946 PG 4 WC Chemistry, Organic SC Chemistry GA YY374 UT WOS:000072140700019 ER PT S AU Biessmann, H Walter, MF Mason, JM AF Biessmann, H Walter, MF Mason, JM BE Chadwick, DJ Cardew, G TI Drosophila telomere elongation SO TELOMERES AND TELOMERASE SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Telomeres and Telomerase CY FEB 25-27, 1997 CL LONDON, ENGLAND ID BROKEN CHROMOSOME ENDS; HET-A RETROPOSONS; SACCHAROMYCES-CEREVISIAE; DNA-SEQUENCES; ATAXIA-TELANGIECTASIA; MELANOGASTER; ELEMENT; TRANSPOSON; PROTEIN; LENGTH AB Drosophila melanogaster has an unusual telomere elongation mechanism. Instead of short repeats that are synthesized by telomerase, long retrotransposons, HeT-A and TART, transpose to the ends of chromosomes. This mechanism generates tandem arrays of these elements at the chromosome ends, in which all elements are oriented with their oligo(A) rails towards the centromere. Structural features of HeT-A and TART elements may provide clues as to their transposition mechanism. Drosophila telomere length polymorphism is mainly due to terminal retrotransposon arrays that differ between chromosome rips and that change with time. In addition, stable terminal chromosome deletions can be generated that do not contain terminal HeT-A and TART arrays, suggesting that, unlike the equivalent terminal repeats in yeast and humans, the presence and length of terminal arrays in Drosophila may not be critical for cell cycle progression. C1 Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Biessmann, H (reprint author), Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. NR 43 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-97278-9 J9 CIBA F SYMP PY 1998 VL 211 BP 53 EP 67 PG 15 WC Biochemistry & Molecular Biology; Medicine, General & Internal SC Biochemistry & Molecular Biology; General & Internal Medicine GA BL63Y UT WOS:000076141700008 ER PT J AU Debiec-Rychter, M Tada, M Poirier, MC Wang, CY AF Debiec-Rychter, M Tada, M Poirier, MC Wang, CY TI DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives of 2-aminofluorene and 4-aminobiphenyl SO TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS LA English DT Article DE mammary epithelium; 2-aminofluorene; 4-aminobiphenyl; N-acetyltransferase; DNA adduct; rat; human ID REPAIR SYNTHESIS; CARCINOGENIC ARYLAMINES; METABOLIC-ACTIVATION; URINARY-BLADDER; GLAND; CELLS; PERSISTENCE; GENOTYPE; INVIVO AB Primary cultures of rat mammary epithelium and the human mammary cell line MCF-12 were incubated with 10 mu M N-formyl-, N-acetyl-, or N-propionyl-derivatives of N-hydroxy-2-aminofluorene (N-OH-AF) or N-formyl-, or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl (N-OH-ABP), in the medium with or without 100 mu M paraoxon, for 3 h. Carcinogen-DNA adducts in the nuclei were detected with an immunohistochemical method using polyclonal antibodies against N-(deoxyguano-8-yl)-2-aminofluorene and ABP-DNA adducts. The relative amounts of adducts per nucleus were determined by image analysis. After treatment, more than 90% of the cells that were attached on the coverslip were alive, as determined by the trypan blue exclusion. All carcinogens produced adducts in both human and rat cells. Adduct formation by the formyl, but not the acetyl or porpionyl, derivatives was inhibited up to 65% by paraoxon. These results demonstrate that both acetyl and propionyl derivatives are primarily activated by cytosolic acetyltransferases and the formyl derivatives may be equally activated by the acetyltransferases and microsomal carboxylesterases. Additionally, the results suggest that exposure to aromatic amines may be a risk factor for human breast cancer. (C) 1998 Wiley-Liss, Inc. C1 SUNY Hlth Sci Ctr, Dept Urol, Syracuse, NY 13210 USA. Aichi Canc Ctr, Res Inst, Biochem Lab, Nagoya, Aichi 464, Japan. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Wang, CY (reprint author), SUNY Hlth Sci Ctr, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. FU NCI NIH HHS [CA23386, CA23800] NR 20 TC 2 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-3211 J9 TERATOGEN CARCIN MUT JI Teratogenesis Carcinog. Mutagen. PY 1998 VL 18 IS 1 BP 35 EP 39 DI 10.1002/(SICI)1520-6866(1998)18:1<35::AID-TCM5>3.0.CO;2-F PG 5 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA ZJ785 UT WOS:000073252900005 PM 9586769 ER PT J AU Shaw, GM Todoroff, K Velie, EM Lammer, EJ AF Shaw, GM Todoroff, K Velie, EM Lammer, EJ TI Maternal illness, including fever, and medication use as risk factors for neural tube defects SO TERATOLOGY LA English DT Article ID BIRTH-DEFECTS; HYPERTHERMIA; POPULATION; PREGNANCY; EXPOSURE AB We investigated if selected maternal illnesses or medications used during the periconceptional period increased risk of having neural tube defect (NTD)-affected pregnancies. We used a population-based case-control study of fetuses and liveborn infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 538 (88% of eligible) NTD cases and 539 (88%) nonmalformed controls, usually within 5 months of delivery. A maternal fever or febrile illness episode in the first trimester was associated with an increased risk for having a NTD-affected pregnancy, odds ratio (OR) = 1.91 (95% confidence interval, 1.35-2.72) for fever and OR = 2.02 (1.20-3.43) for febrile illness. Risk estimates were not substantially altered after adjustment for maternal age, race/ethnicity, education, vitamin use, and body mass index. Other reported illnesses were generally not associated with risks of 1.5 or greater, or were too infrequent to adequately estimate risk. An OR of 1.5 or greater was observed for maternal use of guaifenesin, OR = 2.04 (0.79-5.28), and an OR of 0.5 or less was observed for maternal use of calcium-containing medicines, OR = 0.38 (0.14-1.03). Our findings are consistent with previous reports that suggested elevated NTD risks from maternal fever. We could not discriminate, however, whether the increased risks observed for maternal fever were indicative of a causal relation or due to reporting bias. Our findings suggest that many of the illnesses common to reproductive-aged women and the medications commonly used to treat them during pregnancy, except, perhaps, for those illnesses that are febrile-related, do not appear to substantially contribute to the occurrence of NTDs in the population. (C) 1998 Wiley-Liss, Inc. C1 March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Childrens Hosp, Dept Med Genet, Oakland, CA 94609 USA. RP Shaw, GM (reprint author), March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, 1900 Powell St,Suite 1050, Emeryville, CA 94608 USA. NR 26 TC 88 Z9 92 U1 2 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD JAN PY 1998 VL 57 IS 1 BP 1 EP 7 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA YZ180 UT WOS:000072228300001 PM 9516745 ER PT J AU Kauffman, RD Schmidt, PM Rall, WF Hoeg, JM AF Kauffman, RD Schmidt, PM Rall, WF Hoeg, JM TI Effect of 3- and 4-day FSH superovulation treatments on the in vivo development of vitrified rabbit morulae SO THERIOGENOLOGY LA English DT Meeting Abstract C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RI Rall, William/C-5104-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD JAN 1 PY 1998 VL 49 IS 1 BP 379 EP 379 DI 10.1016/S0093-691X(98)90732-4 PG 1 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA YT213 UT WOS:000071577200243 ER PT S AU Spring, KR Kovbasnjuk, ON Gibson, CC Bungay, PM AF Spring, KR Kovbasnjuk, ON Gibson, CC Bungay, PM BE Cogswell, CJ Conchello, JA Lerner, JM Lu, T Wilson, T Katzir, A TI Application of a novel 8x8 PMT-array detector to light microscopy SO THREE-DIMENSIONAL AND MULTIDIMENSIONAL MICROSCOPY: IMAGE ACQUISITION AND PROCESSING V, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on 3-Dimensional and Multidimensional Microscopy - Image Acquisition and Processing V CY JAN 27-29, 1998 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers, Int Biomed Opt Soc, Santa Barbara Instrument Grp, Kaiser Opt Syst Inc DE multi-anode photo-multiplier; photoactivation; caged fluorescent dye; diffusion; photon counting; pulsed UV laser AB A multi-anode photomultiplier tube (PMT) attached to a light microscope was used to measure the low-light-level signals from fluorescent dyes trapped in the extracellular spaces between living, cultured kidney epithelial cells. The detection assembly utilized photon counting of all 64 channels (maximum count rate 2 MHz) to record the fluorescence produced after the photoactivation of caged fluorophores of different molecular weight and charge. Photoactivation was accomplished by a brief (5ns, 0.5 mJ) pulse of light at 355 nm from a frequency-tripled Nd: YAG laser. Fluorescence of the uncaged fluorophores was excited by the output of an argon laser equipped with an acousto-optical tunable filter for control of wavelength and power. Diffusion coefficients for the fluorescent indicators in the extracellular spaces were calculated from the spatial and temporal decay of the fluorescence after uncaging of the dye in a small region (3 mu M diameter spot) of the 30-90 mu M-diameter microscope field. The system magnification was adjusted so that each 2.5-mm square PMT channel corresponded to a 12.5-mu m square region of the microscope field. The spatial decay of the fluorescence was obtained by sampling multiple adjacent PMT channels, while the temporal decay was determined from the PMT channel encompassing the uncaging site. C1 NIH, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NIH, 10-6N260, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2700-4 J9 P SOC PHOTO-OPT INS PY 1998 VL 3261 BP 17 EP 20 PG 4 WC Engineering, Biomedical; Microscopy; Optics; Spectroscopy SC Engineering; Microscopy; Optics; Spectroscopy GA BL26U UT WOS:000074939600003 ER PT S AU Meyer, RC Spangler, EL Kametani, H Ingram, DK AF Meyer, RC Spangler, EL Kametani, H Ingram, DK BE Harman, D Holliday, R Meydani, M TI Age-associated memory impairment - Assessing the role of nitric oxide SO TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Towards Prolongation of the Healthy Life Span - Practical Approaches to Intervention CY AUG 15-18, 1997 CL ADELAIDE, AUSTRALIA SP 7th Congress Int Assoc Biomed Gerontol ID D-ASPARTATE RECEPTOR; 14-UNIT T-MAZE; INDUCED LEARNING IMPAIRMENT; FREELY MOVING RATS; ALZHEIMERS-DISEASE; SYNTHASE ACTIVITY; CHOLINERGIC HYPOTHESIS; NMDA RECEPTORS; D-CYCLOSERINE; INHIBITION AB Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance ot F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors, We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors, No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release, Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats. C1 NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Fukuoka Prefectural Univ, Dept Psychol, Fukuoka, Japan. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, NIH, Johns Hopkins Bayview Campus,5600 Nathan Shock La, Baltimore, MD 21224 USA. EM doni@vax.grc.nia.nih.gov NR 62 TC 24 Z9 26 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-108-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 854 BP 307 EP 317 DI 10.1111/j.1749-6632.1998.tb09911.x PG 11 WC Geriatrics & Gerontology; Multidisciplinary Sciences SC Geriatrics & Gerontology; Science & Technology - Other Topics GA BM29P UT WOS:000078303400027 PM 9928439 ER PT J AU Shibata, MA Jorcyk, CL Liu, ML Yoshidome, K Gold, LG Green, JE AF Shibata, MA Jorcyk, CL Liu, ML Yoshidome, K Gold, LG Green, JE TI The C3(1)/SV40 T antigen transgenic mouse model of prostate and mammary cancer SO TOXICOLOGIC PATHOLOGY LA English DT Article ID STEROID-BINDING-PROTEIN; LARGE-TUMOR-ANTIGEN; INTRAEPITHELIAL NEOPLASIA; RETINOBLASTOMA GENE; MEDICAL PROGRESS; BREAST-CANCER; C-3 GENES; MICE; CARCINOMA C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629, Bethesda, MD 20892 USA. NR 35 TC 37 Z9 37 U1 0 U2 5 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 1998 VL 26 IS 1 BP 177 EP 182 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA YX683 UT WOS:000072066000021 PM 9502400 ER PT J AU Dragan, Y Klaunig, J Maronpot, R Goldsworthy, T AF Dragan, Y Klaunig, J Maronpot, R Goldsworthy, T TI Meeting overview - Mechanisms of susceptibility to mouse liver carcinogenesis SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material C1 Univ Wisconsin, Dept Oncol, Madison, WI 53706 USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Dragan, Y (reprint author), Univ Wisconsin, Dept Oncol, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 1998 VL 41 IS 1 BP 3 EP 7 PG 5 WC Toxicology SC Toxicology GA ZC636 UT WOS:000072601400001 ER PT J AU Melnick, RL Kohn, MC Dunnick, JK Leininger, JR AF Melnick, RL Kohn, MC Dunnick, JK Leininger, JR TI Regenerative hyperplasia is not required for liver tumor induction in female B6C3F(1) mice exposed to trihalomethanes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MALE F344 RATS; CELL-PROLIFERATION; DRINKING-WATER; CORN-OIL; HEPATIC MICROSOMES; AD-LIBITUM; CHLOROFORM; TOXICITY; GAVAGE; BROMODICHLOROMETHANE AB Chloroform (TCM), a water disinfection by-product, induced liver tumors in female mice when administered by gavage in corn oil but not when given in drinking water at comparable daily doses. Because short-term studies showed that the gavage doses also induced liver toxicity, it has been suggested that the liver tumor response occurs secondary to cytotoxicity and consequent regenerative hyperplasia induced by oxidative metabolism of TCM to the toxic dihalocarbonyl intermediate. This study compares dose-response relationships of gavage-administered chlorinated/ brominated trihalomethanes for hepatotoxicity, replicative DNA synthesis, and hepatocarcinogenicity in female B6C3F(1) mice. The liver tumor data were obtained from previously published studies. Because bromine is a better leaving group than chlorine, metabolism of bromodichloromethane (BDCM) should produce the same intermediates as would be formed from TCM. Hence, the toxicity and carcinogenicity of BDCM was expected to be qualitatively similar to that of TCM. Dose responses for liver weight, serum sorbitol dehydrogenase and alanine aminotransferase (ALT) activities, hepatocyte degeneration, and hepatocyte labeling index (LI, a measure of replicative DNA synthesis) in female mice were similar following 3 weeks of gavage administration (once per day, 5 days per week) with TCM, BDCM, or chlorodibromomethane (CDBM). Fits of composite data for these trihalomethanes to a Hill equation model revealed sigmoidal dose responses for ALT activity and hepatocyte LI and a nearly linear low-dose response for liver tumor incidence. For this family of chemicals, the mouse liver tumor response was not associated with an elevated hepatocyte LI at doses of approximately 1 mmol/kg or less. High incidences of liver tumors were observed,vith BDCM and CDBM at doses that had a marginal effect or no effect on the hepatocyte LI. Thus, the carcinogenic effects of trihalomethanes are not simply a consequence of cytotoxicity and regenerative hyperplasia. The possible contributions from other activation pathways, including GSH conjugation and reductive metabolism, need to be considered in assessments of the carcinogenicity of the trihalomethanes. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 39 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN PY 1998 VL 148 IS 1 BP 137 EP 147 DI 10.1006/taap.1997.8302 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YV620 UT WOS:000071845400017 PM 9465273 ER PT J AU Klein, HG Dodd, RY Dzik, WH Luban, NL Ness, PM Pisciotto, P Schiff, PD Snyder, EL AF Klein, HG Dodd, RY Dzik, WH Luban, NL Ness, PM Pisciotto, P Schiff, PD Snyder, EL TI Current status of solvent/detergent-treated frozen plasma SO TRANSFUSION LA English DT Editorial Material ID HEPATITIS-A VIRUS; POLYMERASE CHAIN-REACTION; FACTOR-VIII; HEMOPHILIACS; BLOOD; RISK; SEROCONVERSION; INACTIVATION; TRANSMISSION; PREVALENCE C1 Amer Assoc Blood Banks, Ad Hoc Comm Solvent Detergent Treated Plasma, Arlington, VA USA. RP Klein, HG (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. NR 27 TC 52 Z9 55 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1998 VL 38 IS 1 BP 102 EP 107 DI 10.1046/j.1537-2995.1998.38198141508.x PG 6 WC Hematology SC Hematology GA YX579 UT WOS:000072054700020 PM 9482404 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial RecJ exonuclease SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID MYCOPLASMA-PNEUMONIAE CYTADHERENCE; PHOSPHOLIPID SYNTHASES; ACCESSORY PROTEINS; ESCHERICHIA-COLI; GENE; PHOSPHORYLATION; IDENTIFICATION; METASTASIS; RESIDUES; DNA C1 Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. EM koonin@ncbi.nlm.nih.gov NR 24 TC 98 Z9 99 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 1998 VL 23 IS 1 BP 17 EP 19 DI 10.1016/S0968-0004(97)01162-6 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU457 UT WOS:000071719400005 PM 9478130 ER PT J AU Clore, GM Gronenborn, AM AF Clore, GM Gronenborn, AM TI Determining the structures of large proteins and protein complexes by NMR SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; TERMINAL SH3 DOMAIN; DNA-BINDING DOMAIN; RESOLUTION 3-DIMENSIONAL STRUCTURE; MULTIDIMENSIONAL NMR; HUMAN THIOREDOXIN; DIRECT REFINEMENT; OLIGOMERIZATION DOMAIN; CHEMICAL-SHIFTS; MIXED DISULFIDE AB Recent advances in multidimensional NMR methodology to obtain H-1, N-15 and C-13 resonance assignments, interproton-distance and torsion-angle restraints, and restraints that Characterize long-range order have, coupled with new methods of structure refinement, permitted solution structures of proteins in excess of 250 residues to be solved. These developments may permit the determination by NMR of the structures of macromolecules up to 50-60 kDa, thereby bringing into reach numerous systems of considerable biological interest, including a large variety of protein-protein and protein-nucleic-acid complexes. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 79 TC 185 Z9 188 U1 3 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JAN PY 1998 VL 16 IS 1 BP 22 EP 34 DI 10.1016/S0167-7799(97)01135-9 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YR665 UT WOS:000071518000006 PM 9470228 ER PT J AU Boguski, MS AF Boguski, MS TI Bioinformatics - a new era SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID SEQUENCE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Boguski, MS (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 26 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PY 1998 SU S BP 1 EP 3 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 135AA UT WOS:000076775700001 ER PT J AU Altschul, SF AF Altschul, SF TI Fundamentals of database searching SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID ACID SUBSTITUTION MATRICES; SEQUENCE DATABASES; AMINO; STATISTICS AB Aligning novel sequences with previously characterized genes or proteins provides important insights into their common attributes and evolutionary origins. The principles underlying the computational tools that can be used to evaluate sequence alignments are discussed. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 16 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PY 1998 SU S BP 7 EP 9 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 135AA UT WOS:000076775700003 ER PT J AU Brownstein, MJ Trent, JM Boguski, MS AF Brownstein, MJ Trent, JM Boguski, MS TI Functional genomics SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID HYBRIDIZATION AB DNA sequence data provided by genome projects have spawned the new field of functional genomics. This approach will yield exciting insights into the pathways to which specific genes belong and will provide clues to their roles in health and disease. C1 NIMH, Genet Sect, Natl Ctr Human Genome Res, NIH, Bethesda, MD 20892 USA. NIH, Canc Genet Branch, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Brownstein, MJ (reprint author), NIMH, Genet Sect, Natl Ctr Human Genome Res, NIH, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PY 1998 SU S BP 27 EP 29 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 135AA UT WOS:000076775700010 ER PT J AU Tessarollo, L Hempstead, BL AF Tessarollo, L Hempstead, BL TI Regulation of cardiac development by receptor tyrosine kinases SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; NEURAL CREST CELLS; C-MET RECEPTOR; HEART DEVELOPMENT; MICE LACKING; TARGETED DISRUPTION; EMBRYONIC LETHALITY; NEUREGULIN RECEPTOR; MESSENGER-RNAS; CHICKEN-EMBRYO AB The development of a functional heart depends on the coordinated growth, differentiation, migration, and apoptosis of cell populations of diverse embryological origins. These processes are regulated in part by soluble polypeptide growth factors that exert their effects via binding to cell surface receptors with intrinsic tyrosine kinase activity. In particular, members of this class of receptors and their ligands have been shown to regulate the development of distinctive regions of the heart, such as the mesodermally derived cardiac myocyte, the endocardium, and outflow tract and septa, which depend on cardiac neural crest. The hepatocyte growth factor receptor, c-met the fibroblast growth factor receptors; and the neuregulin receptors have be en shown to influence cardiomyocyte proliferation and/or differentiation. Receptors binding to vascular endothelial cell growth factor or angiopoietin have been implicated in the development of the endocardium. Finally, gene-targeting experiments in the mouse have demonstrated functional roles for neurotrophins and their cognate trk receptor tyrosine kinases in the development of outflow tract, septa, and valves that are structures derived from cardiac neural crest. (C) 1998 Elsevier Science Inc. C1 Cornell Univ, Coll Med, Dept Med, New York, NY 10021 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Neural Dev Grp, Frederick, MD USA. RP Hempstead, BL (reprint author), Cornell Univ, Coll Med, Dept Med, 1300 York Ave,Room C-606, New York, NY 10021 USA. NR 59 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 1998 VL 8 IS 1 BP 34 EP 40 DI 10.1016/S1050-1738(97)00119-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YY607 UT WOS:000072165200007 PM 21235910 ER PT J AU Lippincott-Schwartz, J Cole, N Presley, J AF Lippincott-Schwartz, J Cole, N Presley, J TI Unravelling Golgi membrane traffic with green fluorescent protein chimeras SO TRENDS IN CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; BREFELDIN-A; 3-DIMENSIONAL ARCHITECTURE; ELECTRON-MICROSCOPY; KDEL RECEPTOR; LIVING CELLS; APPARATUS; TRANSPORT; RETENTION; RETRIEVAL AB An important new tool for investigating how the Golgi receives cargo and maintains its integrity in the face of ongoing secretory traffic has emerged with the advent of green fluorescent protein (GFP) chimeras. GFP chimeras, which cull be visualized in the unperturbed environment of a living cell, are being used in a wine variety of applications to study Golgi dynamics. These include time-lapse imaging, double-label and photobleach experiments. These studies are helping to clarify the steps involved in the formation, translocation and fate of transport intermediates associated with the Golgi complex, including the roles of cytoskeletal elements. They are also providing insights into mechanisms of protein retention and localization within Golgi membranes. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 47 TC 61 Z9 62 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JAN PY 1998 VL 8 IS 1 BP 16 EP 20 DI 10.1016/S0962-8924(97)01199-9 PG 5 WC Cell Biology SC Cell Biology GA YT953 UT WOS:000071663100004 PM 9695802 ER PT J AU McEntyre, J AF McEntyre, J TI Linking up with Entrez SO TRENDS IN GENETICS LA English DT Article C1 NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. RP McEntyre, J (reprint author), NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. NR 3 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JAN PY 1998 VL 14 IS 1 BP 39 EP 40 DI 10.1016/S0168-9525(97)01325-5 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YQ769 UT WOS:000071421400012 PM 9448465 ER PT J AU Cecchini, S Ciatto, S Bonardi, R Mazzotta, A Pacini, P Muraca, MG Zappa, M AF Cecchini, S Ciatto, S Bonardi, R Mazzotta, A Pacini, P Muraca, MG Zappa, M TI Risk of endometrial cancer in breast cancer patients under long-term adjuvant treatment with tamoxifen SO TUMORI LA English DT Article DE breast cancer; cancer screening; endometrial cancer; endometrial cancer diagnosis; multiple cancer; tamoxifen ID UTERUS AB Aims: To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. Methods: A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. Results: A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and Decem ber 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screen-examinations. SIR was 4.0 (95% confidence interval, 1.3-9.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. Conclusions: This study adds evidence to the hypothesis that longterm tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach. C1 Ctr Studio & Prevenz Oncol, I-50131 Florence, Italy. Careggi Hosp, Dept Radiotherapy, Florence, Italy. Natl Canc Inst, Florence Branch, Genoa, Italy. RP Ciatto, S (reprint author), Ctr Studio & Prevenz Oncol, Viale A Volta 171, I-50131 Florence, Italy. EM MD0632@mclink.it NR 15 TC 6 Z9 8 U1 0 U2 1 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD JAN-FEB PY 1998 VL 84 IS 1 BP 21 EP 23 PG 3 WC Oncology SC Oncology GA ZV206 UT WOS:000074281000004 PM 9619708 ER PT J AU Thibault, A Figg, WD Bergan, RC Lush, RM Myers, CE Tompkins, A Reed, E Samid, D AF Thibault, A Figg, WD Bergan, RC Lush, RM Myers, CE Tompkins, A Reed, E Samid, D TI A phase II study of 5-aza-2 ' deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer SO TUMORI LA English DT Article DE angiogenesis; bFGF; chemotherapy; malignancy; tumor biology; tumor markers ID GROWTH-FACTORS; 5-AZA-2'-DEOXYCYTIDINE; ANTIGEN; CELLS AB Aims and Background: Decitabine (5-aza-2'-deoxycytidine) is an S-phase-specific pyrimidine analog with hypomethylation properties. In laboratory models of prostate cancer (PC-3 and DU-145), decitabine induces cellular differentiation and enhanced expression of genes involved in tumor suppression, immunogenicity, and programmed cell death, Methods: We conducted a phase lr study of decitabine in 14 men with progressive, metastatic prostate cancer recurrent after total androgen blockade and flutamide withdrawal. Decitabine was administered at a dose of 75 mg/m(2)/dose IV as a 1 hour infusion every 8 hours for three doses. Cycles of therapy were repeated every 5 to 8 weeks to allow for resolution of toxicity. Results: Two of 12 patients evaluable for response had stable disease with a time to progression of more than 10 weeks. This activity was seen in 2 of 3 African-American patients. Toxicity was similar to previously reported experience. No significant changes in urinary concentrations of the angiogenic factor bFGF, a potential biomarker of tumor activity, were identified over time in 7 unselected patients with progressive disease, Conclusions: We conclude that decitabine is a well tolerated regimen with modest clinical activity against hormone-independent prostate cancer. Further investigations in patients of African-American origin may be warranted. C1 NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Div Clin Sci, Med Branch, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 17 TC 100 Z9 104 U1 1 U2 1 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD JAN-FEB PY 1998 VL 84 IS 1 BP 87 EP 89 PG 3 WC Oncology SC Oncology GA ZV206 UT WOS:000074281000020 PM 9619724 ER PT J AU Lodmell, DL Ray, NB Ewalt, LC AF Lodmell, DL Ray, NB Ewalt, LC TI Gene gun particle-mediated vaccination with plasmid DNA confers protective immunity against rabies virus infection SO VACCINE LA English DT Article DE DNA rabies vaccine; gene gun ID ANTIBODY-RESPONSES; IMMUNIZATION; BOMBARDMENT; ELICITATION; EXPRESSION; VACCINES; MUSCLE; CELLS; MICE AB Accell(R) gene gun particle-mediated immunization with DNA encoding the glycoprotein gene of the challenge virus standard strain of rabies virus was evaluated for its ability to elicit protective levels of serum. anti-rabies virus neutralizing antibody. Strong primary and booster neutralizing antibody responses were detected in mice following immunization with 2 mu g of DNA coated on 2.6-mu m gold beads. Protective levels of antibody persisted for over 300 days. Mice challenged intraplantarly 315 days post-primary immunization (225 days post-booster vaccination) survived lethal rabies virus challenge. Our data demonstrate a potentially significant role for gene gun-based delivery of DNA in the field of rabies virus vaccination. (C) 1997 Published by Elsevier Science Ltd. All rights reserved. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Lodmell, DL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 18 TC 44 Z9 48 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN-FEB PY 1998 VL 16 IS 2-3 BP 115 EP 118 DI 10.1016/S0264-410X(97)88325-9 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YL616 UT WOS:000070974200001 PM 9607018 ER PT J AU Tozzi, AE degli Atti, MLC Wassilak, SGF Salmaso, S Panei, P Anemona, A Luzi, S Greco, D AF Tozzi, AE degli Atti, MLC Wassilak, SGF Salmaso, S Panei, P Anemona, A Luzi, S Greco, D TI Predictors of adverse events after the administration of acellular and whole-cell diphtheria-tetanus-pertussis vaccines SO VACCINE LA English DT Article DE pertussis; acellular vaccine; whole-cell vaccine; DT; safety ID CONTROLLED TRIAL; INJECTION SITE AB Recurrence of adverse events, the effect of sire of injection, and concurrent administration of oral polio vaccine (OPV) and hepatitis B vaccine (HBV) on reactogenicity were assessed in recipients of two acellular pertussis vaccines given in combination with diphtheria and tetanus toxoids (DTaP), one whole-cell DTP vaccine (DTPwc) and one DT vaccine during a double blind, randomized, controlled clinical trial. Local and systemic side reactions were more likely to recur after the administration of DTaP and DT compared with DTPwc, In all vaccine groups, injection in the buttock was associated with a lower rate of common adverse events compared with injection in the thigh, while simultaneous administration of OPV and/or HBV did not increase the risk of onset of side reactions. Published by Elsevier Science Ltd. C1 Ist Super Sanita, Epidemiol & Biostat Lab, Reparto Malattie Infett, I-00161 Rome, Italy. NIAID, NIH, Bethesda, MD 20892 USA. RP Tozzi, AE (reprint author), Ist Super Sanita, Epidemiol & Biostat Lab, Reparto Malattie Infett, Viale Regina Elena 299, I-00161 Rome, Italy. RI Tozzi, Alberto Eugenio/F-9494-2012 OI Tozzi, Alberto Eugenio/0000-0002-6884-984X FU NIAID NIH HHS [N01-AI-25138] NR 12 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN-FEB PY 1998 VL 16 IS 2-3 BP 320 EP 322 DI 10.1016/S0264-410X(97)00163-1 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YL616 UT WOS:000070974200032 PM 9607049 ER PT S AU Gainer, H AF Gainer, H BE Zingg, HH Bourque, CW Bichet, DG TI Cell-specific gene expression in oxytocin and vasopressin magnocellular neurons SO VASOPRESSIN AND OXYTOCIN: MOLECULAR, CELLULAR, AND CLINICAL ADVANCES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT World Congress on Neurohypophysial Hormones CY AUG 08-12, 1997 CL MONTREAL, CANADA SP Canadian Ctr Clin Res & Dev, Wyeth-Ayerst Res, Canada, Wyeth-Ayerst Res, USA, Ferring Pharmaceut, Merck Res Labs, Fujisawa Pharmaceut Co Ltd, Japan Tobacco Inc, Pharmaceut Div, Sanofi Res ID HYPOTHALAMIC SUPRAOPTIC NEURONS; SLICE-EXPLANT CULTURES; DORSAL-ROOT GANGLIA; ARGININE-VASOPRESSIN; TRANSGENIC MICE; ORGANOTYPIC CULTURES; NERVOUS-TISSUE; MESSENGER-RNA; LONG-TERM; RAT AB The oxytocin (OT) and vasopressin (VP) expressing magnocellular neurons in the hypothalamic-neurohypophysial system (HNS) have been the most studied of all the neuroendocrine cell-types. Despite this, our understanding of the mechanisms that underly the cell-specific expression of the peptide genes in these neurons has remained obscure. Part of the reason for this may be related to the close apposition of the OT and VP genes in the chromosomal locus, the genes being separated by as little as 3.5 kb in the mouse, and their interactions which are critical for cell-specific expression of the genes. Recent studies using intact rat OT and VP constructs in transgenic mice, and rat and mouse VP genes with CAT inserts in exon III as reporters in transgenic rats and mice, respectively, have suggested the presence of cell-specific enhancer elements in the 3' downstream (intergenic region, IGR) region of the VP gene. Evidence in favor of this view is presented from transgenic mouse studies on the expression of mouse OT- and VP-CAT gene constructs. Oxytocin and vasopressin phenotypes in the magnocellular neuronal population have traditionally been assessed by either immunocytochemical or in situ hybridization histochemical methods leading to the view that these genes are never coexpressed. However, more sensitive methods show that most OT cells also express some VP mRNA, and most VP cells contain some OT mRNA. A third phenotype containing equivalent levels of both OT and VP mRNA can also be found under some conditions, thereby complicating our analysis of cell-specificity. A continuing problem hindering studies of the regulation of OT and VP gene expression in neurons, is the absence of an appropriate cell line to examine these issues. We have found that stationary slice-explant cultures allow for excellent preservation of highly differentiated magnocellular neurons in long-term culture, and that these cultures can be used for physiological and pharmacological studies and analysis of gene expression. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Room 4D20, Bethesda, MD 20892 USA. NR 58 TC 25 Z9 25 U1 0 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45928-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 449 BP 15 EP 27 PG 13 WC Medicine, Research & Experimental; Neurosciences; Physiology SC Research & Experimental Medicine; Neurosciences & Neurology; Physiology GA BL97F UT WOS:000077323700002 PM 10026782 ER PT S AU Young, WS Shepard, E DeVries, AC Zimmer, A LaMarca, ME Ginns, EI Amico, J Nelson, RJ Hennighausen, L Wagner, KU AF Young, WS Shepard, E DeVries, AC Zimmer, A LaMarca, ME Ginns, EI Amico, J Nelson, RJ Hennighausen, L Wagner, KU BE Zingg, HH Bourque, CW Bichet, DG TI Targeted reduction of oxytocin expression provides insights into its physiological roles SO VASOPRESSIN AND OXYTOCIN: MOLECULAR, CELLULAR, AND CLINICAL ADVANCES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT World Congress on Neurohypophysial Hormones CY AUG 08-12, 1997 CL MONTREAL, CANADA SP Canadian Ctr Clin Res & Dev, Wyeth-Ayerst Res, Canada, Wyeth-Ayerst Res, USA, Ferring Pharmaceut, Merck Res Labs, Fujisawa Pharmaceut Co Ltd, Japan Tobacco Inc, Pharmaceut Div, Sanofi Res ID CORTICOTROPIN-RELEASING FACTOR; FACTOR MESSENGER-RNA; GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS; IMMUNOREACTIVE NEURONS; MATERNAL-BEHAVIOR; VASOPRESSIN; RAT; PARTURITION; ANTAGONISTS AB Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 hours without milk in their stomachs. OT injection into the dams or rescue with the rat OT gene restores the milk ejection in response to suckling. OT is also needed for post-partum alveolar proliferation. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. Furthermore, homozygous mutant mice show reduced aggression in some tests. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Young, WS (reprint author), 36 Convent Dr,MSC 4068, Bethesda, MD 20892 USA. EM scott@zippy.nimh.nih.gov RI Young, W Scott/A-9333-2009; Wagner, Kay-Uwe/B-6044-2009; Zimmer, Andreas/B-8357-2009; OI Young, W Scott/0000-0001-6614-5112; Nelson, Randy/0000-0002-8194-4016 FU NIMH NIH HHS [MH 57535] NR 53 TC 31 Z9 32 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45928-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 449 BP 231 EP 240 PG 10 WC Medicine, Research & Experimental; Neurosciences; Physiology SC Research & Experimental Medicine; Neurosciences & Neurology; Physiology GA BL97F UT WOS:000077323700030 PM 10026810 ER PT S AU Schoneberg, T Kostenis, E Liu, J Gudermann, T Wess, J AF Schoneberg, T Kostenis, E Liu, J Gudermann, T Wess, J BE Zingg, HH Bourque, CW Bichet, DG TI Molecular aspects of vasopressin receptor function SO VASOPRESSIN AND OXYTOCIN: MOLECULAR, CELLULAR, AND CLINICAL ADVANCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT World Congress on Neurohypophysial Hormones CY AUG 08-12, 1997 CL MONTREAL, CANADA SP Canadian Ctr Clin Res & Dev, Wyeth-Ayerst Res, Canada, Wyeth-Ayerst Res, USA, Ferring Pharmaceut, Merck Res Labs, Fujisawa Pharmaceut Co Ltd, Japan Tobacco Inc, Pharmaceut Div, Sanofi Res ID NEPHROGENIC DIABETES-INSIPIDUS; G-PROTEIN; MUSCARINIC RECEPTORS; GENE-MUTATIONS; ACTIVATION; RESCUE; IDENTIFICATION; COEXPRESSION; SPECIFICITY; SELECTIVITY AB The molecular mechanisms governing the G protein coupling selectivity of different members of the vasopressin receptor family were studied by using a combined molecular genetic/biochemical approach. While the V-1a and V-1b vasopressin receptors are selectively linked to G proteins of the G(q/11) class, the V-2 vasopressin receptor is preferentially coupled to G(s). Systematic functional analysis of V-1a/V-2 hybrid receptors showed that the second intracellular loop of the V-1a receptor is required and sufficient for efficient coupling to G(q/11), whereas the third intracellular loop of the V-2 receptor is required and sufficient for coupling to G(s). By using a strategy involving the coexpression of the wildtype V-1a receptor with chimeric G protein alpha(s)/alpha(q) subunits, two C-terminal alpha(q/11) residues were identified that are critical for proper receptor recognition. We previously demonstrated -in transiently transfected COS-7 cells- that selected mutant V-2 vasopressin receptors (all of which have been identified in X-linked nephrogenic diabetes insipidus patients) containing inactivating mutations in the C-terminal third of the receptor protein (including missense, frameshift, or nonsense mutations) can be functionally rescued by coexpression with a C-terminal V-2 receptor fragment (V2-tail) spanning the region where the various mutations occur. Co-immunoprecipitation experiments and a newly developed sandwich ELISA revealed that the V2-tail polypeptide directly interacts with the mutant V-2 receptors thus creating a functional receptor protein. To study the potential therapeutic usefulness of these findings, CHO cell lines stably expressing low levels of functionally inactive mutant V-2 vasopressin receptors (E242stop, Y280C, and W284stop) were created and infected with a recombinant adenovirus coding for the V2-tail polypeptide. Following adenovirus infection, arginine vasopressin (AVP) gained the ability to stimulate cAMP formation in all CHO cell clones studied. Adenovirus-mediated gene transfer also proved to be a highly efficient method to achieve expression of the V2-tail fragment las well as of the wild type V-2 vasopressin receptor) in MDCK renal tubular cells. We therefore speculate that the targeted expression of receptor fragments in vivo may represent a novel strategy in the treatment of human diseases caused by inactivating mutations in distinct G protein-coupled receptors. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Schoneberg, T (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 40 TC 18 Z9 19 U1 0 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45928-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 449 BP 347 EP 358 PG 12 WC Medicine, Research & Experimental; Neurosciences; Physiology SC Research & Experimental Medicine; Neurosciences & Neurology; Physiology GA BL97F UT WOS:000077323700044 PM 10026824 ER PT S AU Hahm, SH Eiden, LE AF Hahm, SH Eiden, LE BE Forssmann, WG Said, SI TI Cis-regulatory elements controlling basal and inducible VIP gene transcription SO VIP, PACAP, AND RELATED PEPTIDES: THIRD INTERNATIONAL SYMPOSIUM SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Symposium on VIP, PACAP, and Related Peptides CY SEP 17-20, 1997 CL FREIBURG, GERMANY SP Amylin Pharmaceut, San Diego, Bayer AG, Wuppertal, Boehringer Mannheim GmBh, Mannheim, Dr Falk Pharma Gmbh, Hannover, Hoechst Marion Roussel, Frankfurt, Hoechst Marion Roussel Inc, Cincinnati, Immunodiagnostik GmBh, Bensheim, Itoham Foods Inc, Ibaraki, Madaus AG, Koln, Neosystem, Strasbourg, Peninsula Labs Inc, Belmont, Perkin Elmer, Appl Biosyst GmBh, Wetterstadt, Schering AG, Berlin, Solvay Pharmaceut GmBh, Hannover, Tap Holdings Inc, Deerfield, Wherl Gmbh, Wolfenbuttel ID VASOACTIVE INTESTINAL POLYPEPTIDE; CYTOKINE RESPONSE ELEMENT; BOVINE CHROMAFFIN CELLS; PEPTIDE GENE; CYCLIC-AMP; ENKEPHALIN BIOSYNTHESIS; ELECTRICAL-ACTIVITY; NEUROPEPTIDE GENES; SIGNALING PATHWAYS; TRANSGENIC MICE AB The cis-acting elements of the VIP gene important for basal and stimulated transcription have been studied by transfection of VIP reporter gene constructs into distinct human neuroblastoma cell lines in which VIP transcription is constitutively high, or can be induced to high levels by protein kinase stimulation. The 5.2 kb flanking sequence of the VIP gene conferring correct basal and Inducible VIP gene expression onto a reporter gene In these cell lines was systematically deleted to define its minimal components. A 425-bp fragment (-4656 to -4251) fused to the proximal 1.55 kb of the VZP promoter-enhancer was absolutely required for cell-specific basal and inducible transcription. Four additional components of the VIP gene were required for full cell-specific expression driven by the 425 bp TSE (region A). Sequences from -155 to -137 (region B), -1.37 to -1.28 (region C), -1.28 to -.094 (region D), and the CRE-containing proximal 94 bp (region E) were deleted In various combinations to demonstrate the specific contributions of each region to correct basal and inducible VIP gene expression. Deletion of region B, or mutational inactivation of the CRE in region E, resulted in constructs with low transcriptional activity in VIP-expressing cell lines. Deletion of regions B and C together resulted In a gain of transcriptional activity, but without cell specificity. All five domains of the VIP gene were also required for cell-specific induction of VIP gene expression with phorbol ester. Gelshift analysis of putative regulatory sequences in regions A-D suggests that both ubiquitous and neuron-specific trans-acting proteins participate in VIP gene regulation. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bldg 36,Rm 3A-10, Bethesda, MD 20892 USA. EM eiden@codon.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 49 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-154-5; 1-57331-153-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 865 BP 10 EP 26 DI 10.1111/j.1749-6632.1998.tb11158.x PG 17 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Pharmacology & Pharmacy; Physiology GA BM29V UT WOS:000078306200002 PM 9927992 ER PT S AU Brenneman, DE Glazner, G Hill, JM Hauser, J Davidson, A Gozes, I AF Brenneman, DE Glazner, G Hill, JM Hauser, J Davidson, A Gozes, I BE Forssmann, WG Said, SI TI VIP neurotrophism in the central nervous system: Multiple effectors and identification of a femtomolar-acting neuroprotective peptide SO VIP, PACAP, AND RELATED PEPTIDES: THIRD INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on VIP, PACAP, and Related Peptides CY SEP 17-20, 1997 CL FREIBURG, GERMANY SP Amylin Pharmaceut, San Diego, Bayer AG, Wuppertal, Boehringer Mannheim GmBh, Mannheim, Dr Falk Pharma Gmbh, Hannover, Hoechst Marion Roussel, Frankfurt, Hoechst Marion Roussel Inc, Cincinnati, Immunodiagnostik GmBh, Bensheim, Itoham Foods Inc, Ibaraki, Madaus AG, Koln, Neosystem, Strasbourg, Peninsula Labs Inc, Belmont, Perkin Elmer, Appl Biosyst GmBh, Wetterstadt, Schering AG, Berlin, Solvay Pharmaceut GmBh, Hannover, Tap Holdings Inc, Deerfield, Wherl Gmbh, Wolfenbuttel ID VASOACTIVE-INTESTINAL-PEPTIDE; RAT CORTICAL ASTROCYTES; NEURONAL SURVIVAL; CELL-DEATH; CULTURES; DISEASE; BRAIN AB Vasoactive intestinal peptide has neurotrophic and growth-regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta-amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial-derived substances released by VIP, These substance include cytokines, protease nexin I, and ADNF, a novel neuro protective protein with structural similarities to heat-shock protein 60, Antiserum against ADNF produced neuronal cell death and an increase in apoptotic neurons in cell culture, A 14 amino acid peptide (ADNF-14) derived from ADNF has been discovered that mimics the survival-promoting action of the parent protein,These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease. C1 NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Brenneman, DE (reprint author), NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 24 TC 29 Z9 31 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-153-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 865 BP 207 EP 212 DI 10.1111/j.1749-6632.1998.tb11180.x PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Pharmacology & Pharmacy; Physiology GA BM29V UT WOS:000078306200024 PM 9928014 ER PT S AU Moody, TW Leyton, J Gozes, I Lang, L Eckelman, WC AF Moody, TW Leyton, J Gozes, I Lang, L Eckelman, WC BE Forssmann, WG Said, SI TI VIP and breast cancer SO VIP, PACAP, AND RELATED PEPTIDES: THIRD INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on VIP, PACAP, and Related Peptides CY SEP 17-20, 1997 CL FREIBURG, GERMANY SP Amylin Pharmaceut, San Diego, Bayer AG, Wuppertal, Boehringer Mannheim GmBh, Mannheim, Dr Falk Pharma Gmbh, Hannover, Hoechst Marion Roussel, Frankfurt, Hoechst Marion Roussel Inc, Cincinnati, Immunodiagnostik GmBh, Bensheim, Itoham Foods Inc, Ibaraki, Madaus AG, Koln, Neosystem, Strasbourg, Peninsula Labs Inc, Belmont, Perkin Elmer, Appl Biosyst GmBh, Wetterstadt, Schering AG, Berlin, Solvay Pharmaceut GmBh, Hannover, Tap Holdings Inc, Deerfield, Wherl Gmbh, Wolfenbuttel ID VASOACTIVE INTESTINAL POLYPEPTIDE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; MAP KINASE; RECEPTOR; PEPTIDE; PACAP; CELLS; LUNG AB VIP1 receptors are present in breast cancer cells, VIP elevates the cAMP and stimulates nuclear oncogene expression in MCF-7 cells, VIPhybrid is a VIP receptor antagonist that inhibits breast cancer proliferation, A VIP analog has been developed for imaging breast tumors. Therefore VIP1 receptors may be utilized for the early detection and treatment of breast cancer. C1 NCI, Med Branch, Rockville, MD 20850 USA. Tel Aviv Univ, Dept Chem Pathol, Tel Aviv, Israel. Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD USA. RP Moody, TW (reprint author), NCI, Med Branch, Bldg KWC,Rm 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 28 TC 23 Z9 23 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-153-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 865 BP 290 EP 296 DI 10.1111/j.1749-6632.1998.tb11189.x PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Pharmacology & Pharmacy; Physiology GA BM29V UT WOS:000078306200033 PM 9928023 ER PT S AU Schutz, B Schafer, MKH Eiden, LE Weihe, E AF Schutz, B Schafer, MKH Eiden, LE Weihe, E BE Forssmann, WG Said, SI TI VIP and NPY expression during differentiation of cholinergic and noradrenergic sympathetic neurons SO VIP, PACAP, AND RELATED PEPTIDES: THIRD INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on VIP, PACAP, and Related Peptides CY SEP 17-20, 1997 CL FREIBURG, GERMANY SP Amylin Pharmaceut, San Diego, Bayer AG, Wuppertal, Boehringer Mannheim GmBh, Mannheim, Dr Falk Pharma Gmbh, Hannover, Hoechst Marion Roussel, Frankfurt, Hoechst Marion Roussel Inc, Cincinnati, Immunodiagnostik GmBh, Bensheim, Itoham Foods Inc, Ibaraki, Madaus AG, Koln, Neosystem, Strasbourg, Peninsula Labs Inc, Belmont, Perkin Elmer, Appl Biosyst GmBh, Wetterstadt, Schering AG, Berlin, Solvay Pharmaceut GmBh, Hannover, Tap Holdings Inc, Deerfield, Wherl Gmbh, Wolfenbuttel ID TRANSPORTER; RAT C1 Univ Marburg, Inst Anat & Cell Biol, D-35033 Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Schutz, B (reprint author), Univ Marburg, Inst Anat & Cell Biol, Robert Koch Str 6, D-35033 Marburg, Germany. OI Eiden, Lee/0000-0001-7524-944X NR 7 TC 13 Z9 14 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-153-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 865 BP 537 EP 541 DI 10.1111/j.1749-6632.1998.tb11232.x PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Pharmacology & Pharmacy; Physiology GA BM29V UT WOS:000078306200076 PM 9928065 ER PT J AU Le, SY Liu, WM Maizel, JV AF Le, SY Liu, WM Maizel, JV TI Phylogenetic evidence for the improved RNA higher-order structure in internal ribosome entry sequences of HCV and pestiviruses SO VIRUS GENES LA English DT Article DE translational control; internal ribosome entry site; RNA structure; phylogenetic comparison; HCV and pestivirus ID HEPATITIS-C VIRUS; SECONDARY STRUCTURES; CULTURED-CELLS; TRANSLATION; INITIATION; PREDICTIONS; STABILITY; SITE; EFFICIENCY; PSEUDOKNOT AB The strong requirement for a small segment of the 5'-proximal coding sequence of hepatitis C virus (HCV) is one of the most remarkable features in the internal initiation of HCV mRNA translation. Phylogenetic analysis and RNA folding indicate a common RNA structure of the 5' untranslated region (UTR) of HCV and the animal pestiviruses, including HCV types 1-11, bovine viral diarrhea (BVDV), border disease virus (BDV) and hog cholera (HoCV), Although the common RNA structure shares similar features to that proposed for the internal ribosome entry sequence (IRES) of picornavirus, phylogenetic evidence suggests four new tertiary interactions between conserved terminal hairpin loops and between the terminal hairpin loop of F2b and the short coding sequence for HCV and pestiviruses, We suggest that the higher-order structures of IRES cis-acting elements for HCV and animal pestivirus are composed of stem-loop structures B-C, domains E-H, stem-loop structure J and four additional tertiary interactions. The common structure of IRES elements for these viruses forms a compact structure by these tertiary interactions and stem stacking. The active structural core is centered in the junction domain of E-H that is also conserved in all members of picornaviruses. Our model suggests that the requirement for a small segment of the 5' coding sequence is to form the distinct tertiary structure that facilitates the cis-acting function of the HCV IRES in the internal initiation of the translational control. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 34 TC 10 Z9 10 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1998 VL 17 IS 3 BP 279 EP 295 DI 10.1023/A:1008073905920 PG 17 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 159KG UT WOS:000078171000008 PM 9926403 ER PT J AU Le, SY Maizel, JV AF Le, SY Maizel, JV TI Evolution of a common structural core in the internal ribosome entry sites of picornavirus SO VIRUS GENES LA English DT Article DE internal ribosome entry site; initiation of translation; picornaviridae; phylogeny; evolution ID 5' NONTRANSLATED REGION; HEPATITIS-C VIRUS; TRANSLATION INVITRO; FUNCTIONAL-ANALYSIS; RNA; INITIATION; POLIOVIRUS; INVIVO AB The translational control involving internal ribosome binding occurs in poliovirus (PV), human rhinoviruses (HRV), encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), and hepatitis A virus (HAV). Internal ribosome binding utilizes cis-acting genetic elements of approximately 450 nucleotides (nt) termed the internal ribosome entry sites (IRES) found in these picornaviral 5'-untranslated region (5'UTR). Although these IRES elements are quite different in their primary sequence, a similar folding structure with a conserved 3' structural core exists in the IRES. Phylogenetic analysis and RNA folding of the 5' UTR of picornaviruses, including PV types 1-3, coxsackievirus types A and B, swine vesicular disease virus, echoviruses, enteroviruses (human and bovine), HRV, HAV, EMCV, mengovirus, Theiler's murine encephalomyelitis viruses, FMDV, and equine rhinoviruses, indicates that the predicted conserved structural core is indeed a general structural feature for all members of the picornavirus family. The evolution of a common structural core likely occurred by the gradual addition or deletion of structural domains and elements to preserve a similar tertiary structure that facilitates the utilization of the IRES in specific host-cell environments. C1 NCI, Div Canc Biol Diag & Ctr, Math Biol Lab, NIH, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Div Canc Biol Diag & Ctr, Math Biol Lab, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 17 TC 13 Z9 13 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1998 VL 16 IS 1 BP 25 EP 38 DI 10.1023/A:1007941524143 PG 14 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA ZC703 UT WOS:000072608100003 PM 9562889 ER PT J AU Maldarelli, F Xiang, CS Chamoun, G Zeichner, SL AF Maldarelli, F Xiang, CS Chamoun, G Zeichner, SL TI The expression of the essential nuclear splicing factor SC35 is altered by human immunodeficiency virus infection SO VIRUS RESEARCH LA English DT Article DE human immunodeficiency virus 1; SC35; splicing; gene expression ID POLYMERASE CHAIN-REACTION; REGULATORY PROTEIN ICP27; MESSENGER-RNA; HIV-1 REV; IN-VIVO; DIFFERENTIAL DISPLAY; TYPE-1 INFECTION; SITE SELECTION; SR PROTEINS; SEQUENCES AB In order to identify cellular genes differentially expressed during human immunodeficiency virus 1 (HIV-1) infection, we conducted a screen using differential display. The sequence of one of the clones, 0085, was identical to a sequence present in the RNA splicing factor SC35. Since splicing is an essential point of control during HIV gene expression, we carried out additional experiments to examine SC35 expression during HIV infection. RNA blots confirmed that SC35 RNA was induced following HIV infection; a 2-3-fold increase in expression of SC35 RNA was detected by day 2 of HIV infection. Fluorescence-activated cell-sorting revealed concomitant increases in SC35 protein and double staining studies demonstrated that increases in SC35 protein occurred specifically in the HIV-infected cells. Laser scanning confocal microscopy revealed SC35 was associated with 2 mu m 'nuclear speckles' in both infected and uninfected cells, suggesting that increases in SC35 accumulated in these nuclear structures and that HIV infection did not alter the intracellular distribution of SC35. These findings indicate that an essential splicing factor is induced after HN infection, suggesting that the consequences of HIV infection include alterations in relative levels of a splicing factor. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM zeichner@nih.gov NR 48 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JAN PY 1998 VL 53 IS 1 BP 39 EP 51 DI 10.1016/S0168-1702(97)00130-5 PG 13 WC Virology SC Virology GA ZK869 UT WOS:000073372000004 PM 9617768 ER PT J AU Connaughton, VP Dowling, JE AF Connaughton, VP Dowling, JE TI Comparative morphology of distal neurons in larval and adult zebrafish retinas SO VISION RESEARCH LA English DT Article DE morphology; retina; distal neurons; zebrafish; Danio rerio ID HORIZONTAL CELLS; BRACHYDANIO-RERIO; BIPOLAR CELLS; CARP RETINA; GOLDFISH; PHOTORECEPTORS; MODULATION AB Distal retinal cells from larval (7-10 days postfertilization) and adult zebrafish retinas were cultured in 70% L-15 medium for 4-5 d and comparable cell types identified, Four photoreceptor types were observed in adult retinal cultures, whereas only single cones were isolated from larval retinas, Horizontal cells in both larval and adult cultures were distinguished by their large size and stellate morphology and two subtypes, A and B, were recognized. Bipolar cells were readily identified in adult cultures, but rare in larval cultures. Two bipolar cell types, large and small, were distinguished, Measurements of the various cell types are provided. (C) 1997 Elsevier Science Ltd. C1 MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. UNIV TEXAS, SCH MED, DEPT NEUROBIOL & ANAT, HOUSTON, TX 77030 USA. HARVARD UNIV, DEPT MOL & CELLULAR BIOL, BIOL LABS, CAMBRIDGE, MA 02138 USA. RP NINCDS, NEUROPHYSIOL LAB,NIH,BLDG 36,RM 2C02, 36 CONVENT DR, MSC 4066, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EY 00811, EY 00824, EY 09133] NR 19 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD JAN PY 1998 VL 38 IS 1 BP 13 EP 18 DI 10.1016/S0042-6989(97)00146-6 PG 6 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA YH853 UT WOS:A1998YH85300002 PM 9474371 ER PT J AU Lands, WEM AF Lands, WEM TI Alcohol, calories, and appetite SO VITAMINS AND HORMONES - ADVANCES IN RESEARCH AND APPLICATIONS, VOL 54 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID RESEARCH CLINICS PREVALENCE; UNITED-STATES ADULTS; OXIDOREDUCTION INVIVO; HYDROGEN TRANSFER; NUTRIENT INTAKE; ENERGY-INTAKE; BODY-WEIGHT; FAT STORAGE; ETHANOL; LIVER C1 NIAAA, Div Basic Res, NIH, Bethesda, MD 20892 USA. RP Lands, WEM (reprint author), NIAAA, Div Basic Res, NIH, Bethesda, MD 20892 USA. NR 76 TC 6 Z9 6 U1 3 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 J9 VITAM HORM PY 1998 VL 54 BP 31 EP 49 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BK65V UT WOS:000072972900002 PM 9529972 ER PT J AU Fowler, DH Gress, RE AF Fowler, DH Gress, RE TI CD8(+) T cells of Tc2 phenotype mediate a GVL effect and prevent marrow rejection SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 25th Congress of the International-Society-of-Blood-Transfusion CY JUN 27-JUL 02, 1998 CL OSLO, NORWAY SP Int Soc Blood Transfus ID VERSUS-HOST DISEASE; NECROSIS-FACTOR-ALPHA; CHRONIC MYELOGENOUS LEUKEMIA; CYTOKINE DYSREGULATION; FUNCTIONAL-PROPERTIES; GRAFT-REJECTION; LYMPHOCYTES-T; VETO CELLS; TRANSPLANTATION; MICE AB Donor T cells mediate both beneficial and detrimental immune reactions in the setting of allogeneic BMT (alloBMT). T cells mediate the GVL effect and prevent marrow rejection, but also induce GVHD. In an attempt to favorably influence the balance of these allogeneic responses, we have evaluated the effect of donor CD4(+), Th1/Th2 and CD8(+), Tc1/Tc2 functional T cell subsets in murine marrow transplantation models. Our studies have identified the CD8(+) Tc2 population (which is a cytolytic effector secreting the type II cytokines IL-4, IL-5, and IL-10) as a subset capable of mediating the GVL effect and preventing marrow rejection with reduced GVHD. We have also shown that the Tc2 subset can be generated in humans. These studies indicate that administration of donor CD8(+) T cells of Tc2 phenotype represents a strategy for improving alloBMT outcome. C1 NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Dept Expt Transplantat & Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov NR 60 TC 11 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1998 VL 74 SU 2 BP 331 EP 340 PG 10 WC Hematology SC Hematology GA 106CZ UT WOS:000075113300048 PM 9704464 ER PT S AU Brigger, P Unser, M AF Brigger, P Unser, M BE Laine, AF Unser, MA Aldroubi, A TI Multi-scale B-spline snakes for general contour detection SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Wavelet Applications in Signal and Image Processing VI CY JUL 22-23, 1998 CL SAN DIEGO, CA SP SPIE Int Soc Opt Engn AB Traditional snakes suffer from slow convergence speed (many control points) and difficult to adjust weighting factors for internal energy terms. We propose an alternative formulation using cubic B-splines, where the knot spacing is variable and controlled by the user. A larger knot spacing allows to reduce the number of parameters, which increases optimization speeds. It also eliminates the need for internal energies, which improves user interactivity. The optimization procedure is embedded into a multi-resolution image representation, where the number of snake-points is adapted to the image grid spacing by correctly adjusting the spline knot spacing. Hence, the proposed method provides a multi-scale approach in both the image and parametric contour domain. Our technique provides fast optimization of the initial snake curve and leads to more stable algorithms in noisy imaging environments. Several biomedical examples of applications are included to illustrate the versatility of the method. C1 NIH, Bethesda, MD 20892 USA. RP Brigger, P (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2913-9 J9 P SOC PHOTO-OPT INS PY 1998 VL 3458 BP 92 EP 102 DI 10.1117/12.328127 PG 11 WC Engineering, Electrical & Electronic SC Engineering GA BL91U UT WOS:000077139100009 ER PT J AU Coyle, SL AF Coyle, SL TI Women's drug use and HIV risk: Findings from NIDA's Cooperative Agreement for Community-Based Outreach/Intervention Research Program SO WOMEN & HEALTH LA English DT Editorial Material ID BEHAVIORS; AIDS; INTERVENTION; OUTREACH; POPULATIONS; MODEL C1 NIDA, Community Res Branch, Lexington, KY 40583 USA. RP Coyle, SL (reprint author), NIDA, Community Res Branch, Lexington, KY 40583 USA. NR 24 TC 24 Z9 24 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 1998 VL 27 IS 1-2 BP 1 EP 18 DI 10.1300/J013v27n01_01 PG 18 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA ZU074 UT WOS:000074158600001 PM 9640631 ER PT J AU Stevens, SJ Tortu, S Coyle, SL AF Stevens, SJ Tortu, S Coyle, SL TI Women drug users and HIV prevention: Overview of findings and research needs SO WOMEN & HEALTH LA English DT Article ID AIDS C1 Univ Arizona, SW Inst Res Women, Tucson, AZ 85721 USA. Natl Dev & Res Inst Inc, New York, NY USA. NIDA, Community Res Branch, Washington, DC USA. RP Stevens, SJ (reprint author), Univ Arizona, SW Inst Res Women, Tucson, AZ 85721 USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 1998 VL 27 IS 1-2 BP 19 EP 23 DI 10.1300/J013v27n01_02 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA ZU074 UT WOS:000074158600002 PM 9640632 ER PT S AU Chapman, L AF Chapman, L CA DDHS Interagcy Working Grp Xenotransplantat BE Fishman, J Sachs, D Shaikh, R TI The Draft US Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation SO XENOTRANSPLANTATION: SCIENTIFIC FRONTIERS AND PUBLIC POLICY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Transplantation Biotechnology - A Workshop on International Issues Including the Use of Non-Human Cells, Tissues, and Organs CY MAR 18-20, 1998 CL NEW YORK, NEW YORK SP New York Acad Sci, Org Econ Cooperat & Dev C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. US FDA, Ctr Biol & Review, Bethesda, MD 20014 USA. NIAID, Bethesda, MD 20892 USA. NIH, Off Sci Policy, Bethesda, MD 20892 USA. Hlth Resources Serv Adm, Rockville, MD USA. US Dept HHS, Off Sci Policy, Off Assistant Secretary Planning & Evaluat, Washington, DC 20201 USA. RP Chapman, L (reprint author), CDC, MS G-19,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 1 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-186-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 862 BP 166 EP 170 PG 5 WC Health Care Sciences & Services; Medicine, Research & Experimental; Multidisciplinary Sciences; Transplantation SC Health Care Sciences & Services; Research & Experimental Medicine; Science & Technology - Other Topics; Transplantation GA BM29S UT WOS:000078305000021 ER PT J AU Garfinkel, DJ Curcio, MJ Smith, V AF Garfinkel, DJ Curcio, MJ Smith, V TI Ty mutagenesis SO YEAST GENE ANALYSIS SE METHODS IN MICROBIOLOGY LA English DT Review ID ARTIFICIAL CHROMOSOME LIBRARY; SACCHAROMYCES-CEREVISIAE; YEAST RETROTRANSPOSON; MOUSE GENOME; INTEGRATION; DNA; GENES; AMPLIFICATION; SELECTION; MUTATIONS C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program,Movable Genet Elements Sect, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. Genentech Inc, Dept Mol Biol, S San Francisco, CA 94080 USA. RP Garfinkel, DJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program,Movable Genet Elements Sect, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Frederick, MD 21702 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA J9 METHOD MICROBIOL PY 1998 VL 26 BP 101 EP 117 PG 17 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BK91G UT WOS:000073851500008 ER PT J AU Meyer-Lindenberg, A Gallhofer, B AF Meyer-Lindenberg, A Gallhofer, B TI Somatized depression as a subgroup of fibromyalgia syndrome SO ZEITSCHRIFT FUR RHEUMATOLOGIE LA English DT Article; Proceedings Paper CT International Fibromyalgia Conference CY OCT, 1997 CL BAD NAUHEIM, GERMANY DE fibromyalgia; somatized depression; somatoform disorders; clomipramine ID CONTROLLED TRIAL; PAIN AB An increase of depressive symptoms in fibromyalgia patients has been noted in a number of studies. The etiologic significance of this finding remains, however, controversial. We suggest that a subgroup of patients with this symptom combination may be pragmatically classified as suffering from somatized depression. Clinical indicators such as a family history of depressive disorders, circadian disturbances, pronounced loss of appetite or libido, and chronic psychosocial stressors should be assessed and, if present, prompt the initiation of psychiatric evaluation and treatment including pharmaco- and psychotherapeutic modalities. Other psychiatric diseases arising in the differential diagnosis of fibromyalgia are discussed. C1 NIMH, Unit PET, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Giessen, Zentrum Psychiat, D-35385 Giessen, Germany. RP Meyer-Lindenberg, A (reprint author), NIMH, Unit PET, Clin Brain Disorders Branch, Bldg 10,Room 4C101,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 12 TC 8 Z9 9 U1 1 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0340-1855 J9 Z RHEUMATOL JI Z. Rheumatol. PY 1998 VL 57 SU 2 BP 92 EP 93 PG 2 WC Rheumatology SC Rheumatology GA 154MH UT WOS:000077892600024 PM 10025092 ER PT J AU Kubota, T Aradhya, S Macha, M Smith, ACM Surh, LC Satish, J Verp, MS Johnson, A Christian, SL Ledbetter, DH AF Kubota, T Aradhya, S Macha, M Smith, ACM Surh, LC Satish, J Verp, MS Johnson, A Christian, SL Ledbetter, DH TI Analysis of parent-of-origin specific DNA methylation at SNRPN, and PW71 in tissues: Implication for prenatal diagnosis. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CHILDRENS HOSP EASTERN ONTARIO,OTTAWA,ON,CANADA. SINAI HOSP,BALTIMORE,MD 21215. UNIV CHICAGO,CHICAGO,IL 60637. NR 0 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 31 PY 1997 VL 73 IS 4 BP 1 EP 1 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YH954 UT WOS:A1997YH95400005 ER PT J AU Christian, SL Kubota, T Huang, B Lesser, J Sutcliffe, JS Ledbetter, DH AF Christian, SL Kubota, T Huang, B Lesser, J Sutcliffe, JS Ledbetter, DH TI Uniparental disomy 15: Improved molecular diagnosis and current clinical indications. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 31 PY 1997 VL 73 IS 4 BP 3 EP 3 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YH954 UT WOS:A1997YH95400007 ER PT J AU Steiner, H Fuchs, S Accili, D AF Steiner, H Fuchs, S Accili, D TI D-3 dopamine receptor-deficient mouse: Evidence for reduced anxiety SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE D-3 dopamine receptors; dopamine; knockout; open field; elevated plus maze; anxiety; anxiolytic ID ELEVATED PLUS-MAZE; ETHOPHARMACOLOGICAL ANALYSIS; AGONIST 7-OH-DPAT; MESSENGER-RNA; BEHAVIOR; MICE; RAT; SULPIRIDE; GENE; HYPERACTIVITY AB Mice without functional D-3 dopamine receptors were examined in two animal models for anxiety: the open-field test and the elevated pins-maze test. In the open field, D-3 receptor-deficient mice (D-3(-/-)) entered the center significantly more often than normal (D-3(+/+)) littermates, suggesting an anxiolytic-like effect of the D-3 receptor mutation. Consistent with this finding, D-3(-/-) mice entered open arms of the plus maze significantly more often and longer than D-3(+/+) littermates, but did not differ in closed-arm entries, an index of general activity. Heterozygous (D-3(+/-)) animals showed intermediate behavioral changes. We interpret these results as indicative of reduced anxiety in mice without D-3 receptors. Our findings thus suggest that D-3 dopamine receptors are involved in the regulation of anxiety. (C) 1998 Elsevier Science Inc. C1 NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 36 TC 96 Z9 98 U1 1 U2 1 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 DEC 31 PY 1997 VL 63 IS 1 BP 137 EP 141 DI 10.1016/S0031-9384(97)00430-7 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA YG527 UT WOS:A1997YG52700020 PM 9402626 ER PT J AU Chiou, TJ Zhang, J Ferrans, VJ Tzeng, WF AF Chiou, TJ Zhang, J Ferrans, VJ Tzeng, WF TI Cardiac and renal toxicity of menadione in rat SO TOXICOLOGY LA English DT Article DE menadione; apoptosis; cardiotoxicity; renal toxicity ID CELL-DEATH; ISOLATED HEPATOCYTES; LIPID-PEROXIDATION; MEDIATED TOXICITY; OXIDATIVE STRESS; GROWTH; GLUTATHIONE; HOMEOSTASIS; VITAMIN-K3; INHIBITION AB Menadione induced oxidative stress in cells. The acute and cumulative toxic effects of menadione were evaluated by intravenous injection of the drug in Wistar rats. For evaluation of acute toxicity, single bolus doses of 25, 50, 100 and 150 mg/kg menadione were used. For evaluation of cumulative toxicity, five doses of 100 and 150 mg/kg menadione were injected every other day. Histologic and ultrastructural examinations were made from tissues of kidney, heart, liver, lung, skeletal muscle of foreleg and smooth muscle of stomach. A dose-response relationship was observed in rats whether treated with single or five doses of menadione. Menadione at a dose of 25 mg/kg produced minimal granular degeneration in the tubular cells of the kidney. Menadione at a dose of 50 mg/kg produced minimal granular degeneration in the tubular cells of the kidney and mild pulmonary hemorrhage in the lung. Menadione at doses of 100 and 150 mg/kg produced lesions in the kidney, heart, liver and lung. The characteristic lesions in the kidney included tubular dilatation, formation of protein casts in the lumen of renal tubules, Ca2+ mineralization, vacuolization in proximal and distal tubules, granular degeneration in the cortex and necrosis. Apoptosis was very obvious in kidney from rats treated at 100 and 150 mg/kg menadione. Lesions found in the heart included inflammation, hemorrhage, vacuolization, edema and necrosis. Mitochondria were swollen. Hepatic changes included inflammation, degeneration, vacuolization and necrosis. The only lesion observed in lung was hemorrhage. At the same dose of menadione, structural damage was more severe in kidney than in other organs. The lesions produced by one dose of single injection of the drug were more severe than five doses of multiple injection of menadione in all observed tissues. We conclude that the acute toxicity of menadione is more severe than the cumulative toxicity of menadione. (C) 1997 Elsevier Science Ireland Ltd. C1 Fu Jen Univ, Dept Biol, Taipei, Taiwan. Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. Vet Gen Hosp, Dept Med, Sect Med Oncol, Taipei, Taiwan. NHLBI, Pathol Branch, NIH, Bethesda, MD 20892 USA. RP Tzeng, WF (reprint author), Fu Jen Univ, Dept Biol, Taipei, Taiwan. EM bio1005@fujens.fju.edu.tw NR 38 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 31 PY 1997 VL 124 IS 3 BP 193 EP 202 DI 10.1016/S0300-483X(97)00162-5 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YW588 UT WOS:000071951400004 PM 9482121 ER PT J AU Wynn, TA AF Wynn, TA TI The debate over the effector function of eosinophils in helminth infection: New evidence from studies on the regulation of vaccine immunity by IL-12 SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article; Proceedings Paper CT International Symposium on the Eosinophil in Allergic Inflammation and Parasitic and Infectious Diseases CY JUN 03-06, 1996 CL RIO JANEIRO, BRAZIL SP Acad Brasileira Ciencias, Astra Pharma, Canada, Conselho Nacl Desenvolvimento Cient & Tecnol, Financiadora Estudos & Projetos, Fundacao Coordenacao Aperfeicoamento Pessoal Nivel Super, Glaxo Wellcome, UK, Med Res Council, Canada, NHLI, Imperial Coll Sci Technol & Med OMS, OPAS, Univ Alberta, Pulmonary Res Grp, Canada, Schering Plough, US, Soc Brasileira Farmacol & Terapeut Exptl, Soc Brasileira Microscop Electr, Soc Brasileira Progresso Cienc, Brit Council DE eosinophil; helmint infection; interleukin-12; vaccine; Shistosoma mansoni ID SCHISTOSOMA-MANSONI; LISTERIA-MONOCYTOGENES; IRRADIATED CERCARIAE; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; NITRIC-OXIDE; MICE; INTERLEUKIN-12; PARASITE; INDUCTION AB The production of Th1-type cytokines is associated with strong cell-mediated immunity while Th2-type cytokines are typically involved in the generation of humoral immune responses. In mice vaccinated a single time (1X) with attenuated cercariae of Schistosoma mansoni, the immunity induced is highly dependent on CD4(+) T cells and IFN-gamma. In contrast mice vaccinated multiple times (3X) have decreased IFN-gamma expression, develop a more dominant Th2-type cytokine response as well as protective antibodies which can passively transfer immunity to naive recipients. Previously, we demonstrated the ability of lL-12 a potent IFN-gamma-inducing cytokine to enhance (1X) schistosome cell-mediated immunity when administered during the period of immunization. More recently, we asked what effects IL-12 would have on the development humoral-based immunity. While multiply-immunized/saline-treated mice demonstrated a 70-80% reduction in parasite burden, 3X/IL-12-vaccinated animals displayed an even more striking >90% reduction in challenge infection, with many mice in the later group demonstrating complete protection. Analysis of pulmonary cytokine mRNA responses demonstrated that control challenged mice elicited a dominant Th2-type response, 3X/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3X/IL-12-immunized animals displayed a dominant Th1-type response. The IL-12-treated group also showed a marked reduction in total serum IgE and tissue eosinophilia while SWAP-specific IgG2a and IgG2b Abs were elevated. Interestingly, animals vaccinated with IL-12 also showed a highly significant increase in total Ig titers specific for IrV-5, a known protective antigen. More importantly, 3X/IL-12 serum alone, when transferred to naive mice reduced worm burdens by over 60% while 3X/saline serum transferred significantly less protection. Nevertheless, animals vaccinated in the presence of lL-12 also develop macrophages with enhanced nitric oxide dependent killing activity against the parasites. Together these observations suggest that IL-12, initially described as an adjuvant for cell-mediated immunity may also be used as an adjuvant for promoting both humoral and cell-mediated protective responses. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@nih.gov RI Wynn, Thomas/C-2797-2011 NR 29 TC 9 Z9 9 U1 0 U2 3 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD DEC 30 PY 1997 VL 92 SU S BP 105 EP 108 DI 10.1590/S0074-02761997000800014 PG 4 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA YU762 UT WOS:000071754000014 PM 9698921 ER PT J AU Wolins, N Bosshart, H Kuster, H Bonifacino, JS AF Wolins, N Bosshart, H Kuster, H Bonifacino, JS TI Aggregation as a determinant of protein fate in post-Golgi compartments: Role of the luminal domain of furin in lysosomal targeting SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROPROTEIN PROCESSING ENZYME; INTEGRAL MEMBRANE-PROTEINS; PROHORMONE CONVERTASE PC2; ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; CELL-SURFACE; INVARIANT-CHAIN; INTRACELLULAR TRAFFICKING; ENDOPROTEOLYTIC CLEAVAGE; NETWORK LOCALIZATION AB The mammalian endopeptidase furin is a type 1 integral membrane protein that is predominantly localized to the TGN and is degraded in lysosomes with a t(1/2) = 2-4 h. Whereas the localization of furin to the TGN is largely mediated by sorting signals in the cytosolic tail of the protein, we show here that targeting of furin to lysosomes is a function of the luminal domain of the protein. Inhibition of lysosomal degradation results in the accumulation of high molecular weight aggregates of furin; aggregation is also dependent on the luminal domain of furin. Temperature and pharmacologic manipulations suggest that furin aggregation occurs in the TGN and thus precedes delivery to lysosomes. These findings are consistent with a model in which furin becomes progressively aggregated in the TGN, an event that leads to its transport to lysosomes. Our observations indicate that changes in the aggregation state of luminal domains can be potent determinants of biosynthetic targeting to lysosomes and suggest the possible existence of quality control mechanisms for disposal of aggregated proteins in compartments of the secretory pathway other than the endoplasmic reticulum. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHD, CBMB, NIH, Bldg 18T Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 70 TC 50 Z9 50 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 29 PY 1997 VL 139 IS 7 BP 1735 EP 1745 DI 10.1083/jcb.139.7.1735 PG 11 WC Cell Biology SC Cell Biology GA YP330 UT WOS:000071266100013 PM 9412468 ER PT J AU McCutcheon, M Wehner, N Wensky, A Kushner, M Doan, S Hsiao, L Calabresi, P Ha, T Tran, TV Tate, KM Winkelhake, J Spack, EG AF McCutcheon, M Wehner, N Wensky, A Kushner, M Doan, S Hsiao, L Calabresi, P Ha, T Tran, TV Tate, KM Winkelhake, J Spack, EG TI A sensitive ELISPOT assay to detect low-frequency human T lymphocytes SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ELISPOT; human; cytokine; autoantigen ID MESSENGER-RNA EXPRESSION; MULTIPLE-SCLEROSIS; MYASTHENIA-GRAVIS; INTERFERON-GAMMA; MONONUCLEAR-CELLS; OPTIC NEURITIS; PROTEIN; ACTIVATION; MEMBRANE; RECEPTOR AB We extended the sensitivity of the ELISPOT assay by including an antigen-driven proliferation step prior to a final restimulation with antigen and irradiated antigen presenting cells (APCs). This improved sensitivity made the modified ELISPOT assay better suited to the detection of rare or low frequency T lymphocytes than the standard ELISPOT assay or alternatives such as limiting dilution analysis or in situ hybridization. Use of ELISA-grade plastic or polyvinylidene difluoride (PVDF) plates for the detection of different cytokines improved the signal-to-noise ratio for counting cytokine spots, and use of video computer imaging software improved objective quantitation. Analysis of antigen-reactive peripheral blood mononuclear cells (PBMC) from multiple sclerosis (MS) patients using both the traditional and our modified ELISPOT assay demonstrate a > 10-fold increase in numbers of myelin basic protein (MBP)-responsive T cells detected (an average of less than 1 spot forming cell (SFC) per 2 X 10(5) PBMC with the standard assay compared to 19 SFC per 2 X 10(5) PBMC with the modified assay). In addition, the modified ELISPOT assay could be performed with frozen PBMC, which permitted greater flexibility in sample processing, multiple use of a single sample as an internal standard, and simultaneous analysis of samples collected at different time points. This modified ELISPOT assay has many applications, including analysis of cytokine profiles in rare T cell populations. identification of antigen-responsive individuals as PBMC donors for T lymphocyte cloning or for therapeutic intervention, and assessment of vaccine or therapeutic efficacy as a surrogate clinical marker. (C) 1997 Elsevier Science B.V. C1 Anergen Inc, Redwood City, CA 94063 USA. NINDS, Bethesda, MD 20892 USA. RP Spack, EG (reprint author), Anergen Inc, 301 Penobscot Dr, Redwood City, CA 94063 USA. NR 18 TC 120 Z9 126 U1 2 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 DEC 29 PY 1997 VL 210 IS 2 BP 149 EP 166 DI 10.1016/S0022-1759(97)00182-8 PG 18 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA ZA025 UT WOS:000072320600004 PM 9520298 ER PT J AU Sadoul, K Berger, A Niemann, H Weller, U Roche, PA Klip, A Trimble, WS Regazzi, R Catsicas, S Halban, PA AF Sadoul, K Berger, A Niemann, H Weller, U Roche, PA Klip, A Trimble, WS Regazzi, R Catsicas, S Halban, PA TI SNAP-23 is not cleaved by botulinum neurotoxin E and can replace SNAP-25 in the process of insulin secretion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; SYNAPTOSOMAL-ASSOCIATED PROTEIN; SYNAPTIC VESICLE DOCKING; CLOSTRIDIAL NEUROTOXINS; CHROMAFFIN CELLS; BINDING-PROTEIN; FUSION PROTEIN; SEROTYPE-A; SYNTAXIN; RELEASE AB The synaptosomal-associated protein of 25 kDa (SNAP-25) is expressed in neurons and endocrine cells. It has been shown to play an important role in the release mechanism of neurotransmitters and peptide hormones, including insulin. Thus, when insulin-secreting cells are permeabilized and treated with botulinum neurotoxin E (BoNT/E), SNAP-25 is hydrolyzed, and insulin secretion is inhibited. Recently SNAP-23, a more generally expressed isoform of SNAP-25, has been described. The functional role of SNAP-23 has not been investigated to date. It is now shown that SNAP-23 is resistant to cleavage by BoNT/E. It was therefore possible to test whether transfection of HIT (transformed pancreatic B-) cells with SNAP-23 reconstitutes insulin release from BoNT/E treated cells, in which SNAP-25 is inactivated by the toxin. The results show that SNAP-23 is able to replace SNAP-25 when it is overexpressed. While these results demonstrate that SNAP-23 is a functional homologue of SNAP-25, able to function in regulated exocytosis, they indicate that SNAP-23 may be inefficient in this process. This suggests that both isoforms may have their own specific binding partners and discrete, albeit mechanistically similar, functional roles within the cell. C1 Ctr Med Univ Geneva, Lab Rech Louis Jeantet, CH-1211 Geneva 4, Switzerland. Med Hsch Hannover, Inst Biochem, D-30623 Hannover, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. Inst Biol Cellulaire & Morphol, CH-1005 Lausanne, Switzerland. RP Sadoul, K (reprint author), Ctr Med Univ Geneva, Lab Rech Louis Jeantet, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. RI Sadoul, Karin/N-2649-2013 NR 44 TC 77 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 1997 VL 272 IS 52 BP 33023 EP 33027 DI 10.1074/jbc.272.52.33023 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN575 UT WOS:000071182900045 PM 9407084 ER PT J AU Backlund, PS AF Backlund, PS TI Post-translational processing of RhoA - Carboxyl methylation of the carboxyl-terminal prenylcysteine increases the half-life of RhoA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; FARNESYLCYSTEINE ANALOGS; ADENOSYLHOMOCYSTEINE HYDROLASE; SACCHAROMYCES-CEREVISIAE; SIGNAL TRANSDUCTION; MEMBRANE-BINDING; AMINO-ACIDS; STE14 GENE; A-FACTOR; METHYLTRANSFERASE AB RhoA and related GTP-binding proteins are modified post-translationally at their carboxyl terminus to form a prenylcysteine methyl ester. The synthesis and posttranslational modification of RhoA and Cdc42 were examined in the RAW264 macrophage cell line, and the effect of carboxyl methylation on protein turnover was determined. Cells were labeled with [S-35]cysteine, and RhoA or Cdc42 was immunoprecipitated with specific antibodies. Both RhoA and Cdc42 were methylated rapidly in control cells, with little accumulation of unmethylated protein. Carboxyl methylation of RhoA was inhibited by incubation of cells with a carbocyclic adenosine analog, 3-deazaaristeromycin, resulting in the accumulation of unmethylated RhoA. Under these conditions, Cdc42 methylation was inhibited only partially, When methylation was inhibited, the RhoA half-life decreased from 31 to 12 h, and the Cdc42 half-life decreased from 15 to 11 h. The increased degradation of unmethylated RhoA demonstrates a novel function for carboxyl-terminal prenylcysteine carboxyl methylation in protecting RhoA and related proteins from degradation. C1 NIMH, Lab Genet & Comparat Biochem, Bethesda, MD 20892 USA. RP Backlund, PS (reprint author), NICHD, LCMB, Bldg 10,Rm 10D-14,10 Ctr Dr MSC 1855, Bethesda, MD 20892 USA. NR 42 TC 65 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 1997 VL 272 IS 52 BP 33175 EP 33180 DI 10.1074/jbc.272.52.33175 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN575 UT WOS:000071182900066 PM 9407105 ER PT J AU Lorenzo, PS Bogi, K Acs, P Pettit, GR Blumberg, PM AF Lorenzo, PS Bogi, K Acs, P Pettit, GR Blumberg, PM TI The catalytic domain of protein kinase C delta confers protection from down-regulation induced by bryostatin 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESTER-INDUCED DIFFERENTIATION; PHORBOL-ESTER; TUMOR PROMOTERS; CELLS; ALPHA; DEGRADATION; INHIBITION; RECEPTOR; ISOZYMES; PROTEOLYSIS AB Bryostatin 1 (Bryo) has been shown to induce biphasic dose-response curves for down-regulating protein kinase C delta (PKC delta) as well as for protecting PKC delta from down-regulation induced by phorbol 12-myristate 13-acetate (PMA). To identify regions within PKC delta that confer these responses to Bryo, we utilized reciprocal PKC alpha and PKC delta chimeras (PKC alpha/delta and PKC delta/alpha) constructed by exchanging the regulatory and catalytic domains of these PKCs, These chimeras and wild-type PKC alpha/alpha and PKC delta/delta constructed in the same way were stably expressed in NIH 3T3 fibroblasts. Twenty-four h of treatment with Bryo induced a biphasic dose-response curve for down-regulating both wild-type PKC delta/delta and the PKC alpha/delta chimera. In contrast, Bryo led to a nearly complete down-regulation of both PKC alpha/alpha and PKC delta/alpha and also produced a faster mobility form of these species on SDS-polyacrylamide gel electrophoresis, The nature of both the regulatory and, to a lesser extent, the catalytic domains affected the potency of Bryo to down-regulate the chimeric PKC proteins as well as to protect PKC alpha/delta and PKC delta/delta from down-regulation. Bryo at high concentrations also inhibited the down-regulation of PKC delta/delta and PKC alpha/delta induced by 1 mu M PMA when co-applied, The portion of PKC protected by Bryo from down-regulation by either Bryo or PMA was localized in the particulate fraction of the cells. We conclude that the catalytic domain of PKC delta confers protection from down-regulation induced by Bryo or Bryo plus PMA, suggesting that this domain contains the isotype-specific determinants involved in the unique effect of Bryo on PKC delta. C1 NCI, MMTP, LCCTP, NIH, Bethesda, MD 20892 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. RP Blumberg, PM (reprint author), NCI, MMTP, LCCTP, NIH, Bldg 37,Rm 3A01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 41 TC 38 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 1997 VL 272 IS 52 BP 33338 EP 33343 DI 10.1074/jbc.272.52.33338 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN575 UT WOS:000071182900087 PM 9407126 ER PT J AU Srivastava, RAK Srivastava, N Averna, M Lin, RC Korach, KS Lubahn, DB Schonfeld, G AF Srivastava, RAK Srivastava, N Averna, M Lin, RC Korach, KS Lubahn, DB Schonfeld, G TI Estrogen up-regulates apolipoprotein E (ApoE) gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor alpha-mediated pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; B MESSENGER-RNA; A-I; INBRED STRAINS; PLASMA-LIPOPROTEINS; LDL-RECEPTOR; RAT-LIVER; INVIVO REGULATION; MICE; PROTEIN AB The antiatherogenic property of estrogens is mediated via at least two mechanisms: first by affecting plasma lipoprotein profiles, and second by affecting the components of the vessel wall. Raising plasma apolipoprotein E (apoE) in mice protects them against diet-induced atherosclerosis (Shimano, H., Yamada, N., Katsuki, M., Gotoda, T., Harada, K., Murase, T., Fukuzawa, C., Takaku, F., and Yazaka, Y. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1750-1754). It is possible that estrogen may be antiatherogenic at least in part by increasing plasma apoE levels. Therefore, we studied the regulation of apoE by estrogen. A survey of 15 inbred strains of mice showed that some mouse strains responded to injections or subcutaneously implanted pellets of estradiol by raising their apoB and apoE levels and some did not. We performed detailed studies in two "responder" strains, C57L and C57BL, and two "non-responder" strains, C3H and BALBc. Responders increased their plasma apoE levels 2.5-fold. Non-responders' levels were altered +/-10%. In the responders the distribution of apoE among the plasma lipoproteins shifted from high density lipoprotein toward the apoB-containing lipoprotein fractions. In nonresponders the shift was toward high density lipoprotein. Hepatic apoE mRNA levels and relative rates of apoE mRNA transcription were unchanged in all strains, suggesting that apoE regulation occurred at posttranscriptional loci. Therefore, we measured apoE synthesis in fresh liver slices and on isolated hepatic polysomes. Two-fold increases were noted but only in responders accompanied by selective 1.5-fold increases in polysomal apoE mRNA levels. Similar increases in apoE synthesis were also observed in castrated C57BL mice given either physiological or pharmacological replacement doses of estradiol, but not testosterone, suggesting that the effect of estradiol was specific on the distribution of apoE mRNA in the translationally active polysomal pool. Next, we examined whether the effects of estrogen on apoE translation were mediated by estrogen receptors (ER). ER-alpha knock-out mice and their wild-type littermates were administered estradiol. As expected, apoE levels and hepatic apoE synthesis increased more than 2-fold in the wildtype littermates, but only 20% increases in the plasma apoE and hepatic synthesis were observed in the ER knock-out mice. Hepatic apoE mRNA levels did not change in either the wild-type or the ER knock-out mice. Thus, estradiol up-regulates apoE gene expression by increasing levels of apoE mRNA in the polysomal translating pool. Furthermore, the increased polysomal recruitment of apoE mRNA is largely mediated by estrogen receptors. C1 Washington Univ, Sch Med, Dept Internal Med, Div Atherosclerosis Nutr & Lipid Res, St Louis, MO 63110 USA. Dept Vet Affairs, Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Univ Palermo, Palermo, Italy. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. RP Srivastava, RAK (reprint author), Washington Univ, Sch Med, Dept Internal Med, Div Atherosclerosis Nutr & Lipid Res, 660 S Euclid Ave,Box 8046, St Louis, MO 63110 USA. OI Korach, Kenneth/0000-0002-7765-418X; Averna, Maurizio/0000-0003-3558-9209 FU NHLBI NIH HHS [2RO1HL42460]; NIDDK NIH HHS [P60 DK20579] NR 51 TC 105 Z9 106 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 1997 VL 272 IS 52 BP 33360 EP 33366 DI 10.1074/jbc.272.52.33360 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN575 UT WOS:000071182900090 PM 9407129 ER PT J AU Galinis, DL McKee, TC Pannell, LK Cardellina, JH Boyd, MR AF Galinis, DL McKee, TC Pannell, LK Cardellina, JH Boyd, MR TI Lobatamides A and B, novel cytotoxic macrolides from the tunicate Aplidium lobatum SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Letter C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP McKee, TC (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. NR 8 TC 51 Z9 51 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 26 PY 1997 VL 62 IS 26 BP 8968 EP 8969 DI 10.1021/jo9716237 PG 2 WC Chemistry, Organic SC Chemistry GA YQ657 UT WOS:000071410200004 ER PT J AU Fukamauchi, F Wang, YJ Chuang, DM AF Fukamauchi, F Wang, YJ Chuang, DM TI Ethanol induces subtype-specific up-regulation of muscarinic acetylcholine receptor mRNA in neurohybrid cell lines SO LIFE SCIENCES LA English DT Article DE muscarinic acetylcholine receptor mRNA; ethanol; NG108-15; NCB-20 ID CEREBELLAR GRANULE CELLS; MESSENGER-RNA; BRAIN AB Effects of sub-chronic ethanol treatment on the mRNA levels of muscarinc acetylcholine receptor (mAChR) subtypes were studied in two neurohybrid cell lines, NG108-15 and NCB-20. The former expresses only m4-mAChRs, while the latter expresses m1- and m4-mAChRs. Exposure to 200 mM ethanol for 1 to 3 days induced a time-dependent increase in the levels of m4-mAChR mRNA in NG108-15 and NCB-20 cells. In contrast, the levels of m1-mAChR mRNA and mAChR-mediated phosphoinositide hydrolysis in NCB-20 cells were unchanged. The ethanol-induced up-regulation of m4-mAChR mRNA was associated with a parallel increase in the levels of mAChR binding sites assessed by using [H-3]quinuclidinyl benzilate. The mRNA up-regulation was closely correlated with a decrease in intracellular cyclic AMP concentration and the ethanol up-regulation was blocked by 8-bromo-cyclic AMP and forskolin, suggesting that m4-mAChR mRNA is under negative regulation by cyclic AMP. Thus, neurally-related cell lines are useful models for studying molecular mechanisms underlying ethanol-induced alteration of mAChR expression and function in the nervous system. C1 NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Med Sci, Chiyoda Ku, Tokyo 1010062, Japan. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bldg 10,Room 3N-212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD DEC 26 PY 1997 VL 62 IS 5 BP 389 EP 396 DI 10.1016/S0024-3205(97)01132-6 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA YN183 UT WOS:000071141400002 ER PT J AU Brown, P AF Brown, P TI Spongiform encephalopathies - B lymphocytes and neuroinvasion SO NATURE LA English DT Editorial Material RP Brown, P (reprint author), NINCDS,CNS STUDIES LAB,NIH,BETHESDA,MD 20892, USA. NR 0 TC 27 Z9 28 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 25 PY 1997 VL 390 IS 6661 BP 662 EP 663 DI 10.1038/37733 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YM508 UT WOS:A1997YM50800020 PM 9414158 ER PT J AU Ozaki, M Sasner, M Yano, R Lu, HS Buonanno, A AF Ozaki, M Sasner, M Yano, R Lu, HS Buonanno, A TI Neuregulin-beta induces expression of an NMDA-receptor subunit SO NATURE LA English DT Article ID NEU DIFFERENTIATION FACTOR; ACETYLCHOLINE-RECEPTOR; DEVELOPING CEREBELLUM; GENE-EXPRESSION; MESSENGER-RNAS; SINGLE-CHANNEL; GRANULE CELLS; MUSCLE; ERBB3; SYNAPSES AB Neuregulins (also known as ARLA, NDF, heregulin, GGF) are a family of widely expressed growth and differentiation factors. Neuregulins secreted from motor neurons accumulate at maturing neuromuscular junctions, where they stimulate transcription of genes encoding specific acetylcholine receptors. How these factors function at central synapses, however, is unknown. In the maturing cerebellum, neuregulins are concentrated in glutamatergic messy fibres that innervate granule cells in the internal granule-cell layer(1). We have analysed the effects of neuregulins on the expression of genes encoding NMDA (N-methyl-D-aspartate) receptors in the cerebellum, because receptor composition changes dramatically as expression of the receptor NR2C subunit is specifically induced in neurons in the internal granule-cell layer during synaptogenesis. Here we report that addition of a neuregulin-beta isoform to cultured cerebellar slices specifically increases the expression of NR2C messenger RNAs by at least 100-fold; effects are only minor with a neuregulin-alpha isoform. This stimulation of NR2C expression requires synaptic activity by NMDA receptors, as well as neuregulin-beta. Addition of the NMDA-receptor-channel blocker AP-5 prevents upregulation of the NR2C subunit by neuregulin, whereas an AMPA/kainate-receptor antagonist does not. Consistent with these effects of neuregulin, we find that granule cells express its receptors ErbB2 and ErbB4 before the NR2C subunit of the NMDA receptor. Our results indicate that neuregulins regulate the composition of neurotransmitter receptors in maturing synapses in the brain, in a manner analogous to the neuromuscular junction. C1 NIH,MOL NEUROBIOL UNIT,LDN,BETHESDA,MD 20892. RIKEN,FRONTIER RES PROGRAM,LAB CELLULAR INFORMAT PROC,WAKO,SAITAMA 35101,JAPAN. AMGEN INC,DEPT PROT STRUCT,THOUSAND OAKS,CA 91320. NR 30 TC 206 Z9 213 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 25 PY 1997 VL 390 IS 6661 BP 691 EP 694 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YM508 UT WOS:A1997YM50800033 PM 9414162 ER PT J AU McCann, UD Seiden, LS Rubin, LJ Ricaurte, GA AF McCann, UD Seiden, LS Rubin, LJ Ricaurte, GA TI Brain serotonin neurotoxicity and fenfluramine and dexfenfluramine - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP McCann, UD (reprint author), NIMH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 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 DEC 24 PY 1997 VL 278 IS 24 BP 2142 EP 2142 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YM043 UT WOS:000071022200023 ER PT J AU Xie, D Gulnik, S Collins, L Gustchina, E Suvorov, L Erickson, JW AF Xie, D Gulnik, S Collins, L Gustchina, E Suvorov, L Erickson, JW TI Dissection of the pH dependence of inhibitor binding energetics for an aspartic protease: Direct measurement of the protonation states of the catalytic aspartic acid residues SO BIOCHEMISTRY LA English DT Article ID ISOTHERMAL TITRATION CALORIMETRY; CRYSTAL-STRUCTURES; HIV-1 PROTEASE; ACTIVE-SITE; HUMAN RENIN; IONIZATION STATES; ANTIBODY-BINDING; CATHEPSIN-D; COMPLEX; MECHANISM AB The catalytic activity and inhibitor binding energetics of enzymes are often pi-I-dependent properties. Aspartic proteases comprise an important class of enzyme targets for structure-based drug design. We have performed a complete thermodynamic study of pepstatin binding to plasmepsin II, an aspartic proteinase found in Plasmodium falciparum, using isothermal titration calorimetry and circular dichroism. Thermodynamic parameters (Delta G, Delta H, Delta C-p, and Delta S) were measured as functions of both pH and temperature, In the pH range from 4.5 to 7.0, pepstatin binding is accompanied by proton transfer between the solvent and the complex. We used thermodynamic proton linkage theory to derive both the pH-independent binding energetics for pepstatin and the number and pK(a), values of ionizable residues whose pK(a) values change during ligand binding. These residues were identified as the two catalytic aspartates, with pK(a)s of 6.5 and 3.0, and His 164, with a pK(a) of 7.5, based on the three-dimensional structure of the pepstatin-plasmepsin IT complex. At pH 5.0, where the protease has optimum activity, the proton transfer process contributes almost 40% of the total binding free energy change and the total charge of the active-site aspartic acid residues is -1, These experimental results provide direct measurement for the protonation states of the catalytic aspartates in the presence of bound ligands. Comparison of the thermodynamic and structural data for pepstatin binding with human cathepsin D, a lysosomal aspartic protease that shares 35% sequence identity with plasmepsin IT, suggests that the energetic differences between these two proteins are due to a higher interdomain flexibility in plasmepsin II. C1 NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, SAIC Frederick, Frederick, MD 21702 USA. RP Xie, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, SAIC Frederick, Bldg 322,Rm 27C, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO-56000] NR 39 TC 58 Z9 58 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 23 PY 1997 VL 36 IS 51 BP 16166 EP 16172 DI 10.1021/bi971550l PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP644 UT WOS:000071299600016 PM 9405050 ER PT J AU Ford, HL Silver, DL Kachar, B Sellers, JR Zain, SB AF Ford, HL Silver, DL Kachar, B Sellers, JR Zain, SB TI Effect of Mts1 on the structure and activity of nonmuscle myosin II SO BIOCHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; CALCIUM-BINDING PROTEIN; LIGHT-CHAIN KINASE; HEAVY-CHAIN; CELL-LINE; EPITHELIAL-CELLS; CARCINOMA CELLS; S-100 PROTEIN; MESSENGER-RNA; GENE AB The mts1 gene codes for a 9 kDa protein belonging to the S100 subfamily of Ca2+-binding proteins and is known to play a role in metastasis. Its role in metastasis may be through cellular locomotion, as transfection of mts1 into mouse mammary adenocarcinoma cells increases cellular motility in modified Boyden chemotaxis chambers. The Mts1 protein interacts with nonmuscle myosin II in the presence of Ca2+ with an affinity of approximately 7.9 x 10(4) M-1 and an approximate stoichiometry of 3 mol of Mts1/mol of myosin heavy chain. No interaction was found with myosin I or myosin V. The binding site of Mts1 on myosin is in the rod region, particularly to the light meromyosin portion of the rod, To understand the mechanism by which Mts1 alters cellular motility, we examined its effect on myosin structure and activity. Cosedimentation analysis and electron microscopy suggest that Mts1 destabilizes myosin filaments, In the presence of Ca2+, Mts1 inhibits the actin-activated MgATPase activity of myosin in vitro. The data demonstrate an effect of Mts1 on both myosin structure and function, and suggest a route through which Mts1 affects motility as well as metastasis. C1 Univ Rochester, Dept Biochem, Rochester, NY 14642 USA. Univ Rochester, Ctr Canc, Rochester, NY 14642 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NIDCD, Lab Cellular Biol, Bethesda, MD 20892 USA. RP Ford, HL (reprint author), Dana Farber Canc Inst, Room D810B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA62376, P30CA11198] NR 67 TC 58 Z9 60 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 23 PY 1997 VL 36 IS 51 BP 16321 EP 16327 DI 10.1021/bi971182l PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP644 UT WOS:000071299600033 PM 9405067 ER PT J AU Tsuda, T Kusui, T Jensen, RT AF Tsuda, T Kusui, T Jensen, RT TI Neuromedin B receptor activation causes tyrosine phosphorylation of p125(FAK) by a phospholipase C independent mechanism which requires p21(rho) and integrity of the actin cytoskeleton SO BIOCHEMISTRY LA English DT Article ID SWISS 3T3 CELLS; GASTRIN-RELEASING PEPTIDE; FOCAL ADHESION KINASE; SMOOTH-MUSCLE CELLS; BOMBESIN-LIKE PEPTIDES; GROWTH-FACTORS; ADP-RIBOSYLTRANSFERASE; ANGIOTENSIN-II; DNA-SYNTHESIS; MONOCLONAL-ANTIBODIES AB Recent studies show that tyrosine phosphorylation by a number of neuropeptides may be an important intracellular pathway in mediating changes in cell function, particularly related to growth. Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action. In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides. NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALE 3T3 cells. NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP). The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells. TPA (1 mu M) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB. A23187 potentiated the effect of TPA. Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation. Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+](i), but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X. The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%. However, tyrphostin A25 did not inhibit NMB-stimulated increases in [H-3]inositol phosphates. Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN-and TPA-induced tyrosine phosphorylation of p125(FAK) completely. In contrast, colchicine, an agent which disrupts microtubules, had no effect. Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%. These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK). NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+](i) or PKC. The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK). The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK). These results suggest that similar to some other neuropeptides, activation of this pathway may be an important mechanism in mediating cellular changes by this receptor such as growth. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NR 92 TC 31 Z9 32 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 23 PY 1997 VL 36 IS 51 BP 16328 EP 16337 DI 10.1021/bi971448o PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP644 UT WOS:000071299600034 PM 9405068 ER PT J AU Ibba, M Bono, JL Rosa, PA Soll, D AF Ibba, M Bono, JL Rosa, PA Soll, D TI Archaeal-type lysyl-tRNA synthetase in the Lyme disease spirochete Borrelia burgdorferi SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSFER-RNA SYNTHETASE; ESCHERICHIA-COLI; GENE; SEQUENCE; RECOGNITION; EXPRESSION; EVOLUTION; PROTEIN; FAMILY; VECTOR AB Lysyl-tRNAs are essential for protein biosynthesis by ribosomal mRNA translation in all organisms. They are synthesized by lysyl-tRNA synthetases (EC 6.1.1.6), a group of enzymes composed of two unrelated families. In bacteria and eukarya, all known lysyl-tRNA synthetases are subclass IIc-type aminoacyl-tRNA synthetases, whereas some archaea have been shown to contain an unrelated class I-type lysyl-tRNA synthetase. Examination of the preliminary genomic sequence of the bacterial pathogen Borrelia burgdorferi, the causative agent of Lyme disease, indicated the presence of an open reading frame with over 55% similarity at the amino acid level to archaeal class I-type lysyl-tRNA synthetases. In contrast, no coding region with significant similarity to any class II-type lysyl-tRNA synthetase could be detected. Heterologous expression of this open reading frame in Escherichia coli led to the production of a protein with canonical lysyl-tRNA synthetase activity in vitro. Analysis of B. burgdorferi mRNA showed that the lysyl-tRNA synthetase-encoding gene is highly expressed, confirming that B. burgdorferi contains a functional class I-type lysyl-tRNA synthetase. The detection of an archaeal-type lysyl-tRNA synthetase in B. burgdorferi and other pathogenic spirochetes, but not to date elsewhere in bacteria or eukarya, indicates that the gene that encodes this enzyme has a common origin with its orthologue from the archaeal kingdom. This difference between the lysyl-tRNA synthetases of spirochetes and their hosts may be readily exploitable for the development of anti-spirochete therapeutics. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. RP Soll, D (reprint author), Yale Univ, Dept Mol Biophys & Biochem, POB 208114,266 Whitney Ave, New Haven, CT 06520 USA. EM soll@trna.chem.yale.edu NR 40 TC 85 Z9 86 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14383 EP 14388 DI 10.1073/pnas.94.26.14383 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800031 PM 9405621 ER PT J AU Chanturiya, A Chernomordik, LV Zimmerberg, J AF Chanturiya, A Chernomordik, LV Zimmerberg, J TI Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membrane fusion; membranes; exocytosis; viral fusion ID MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; PLANAR BILAYER; PHOSPHATIDYLETHANOLAMINE LIPOSOMES; CA2+-ACTIVATED SECRETION; ELECTRICAL BREAKDOWN; PHASE-TRANSITION; CELL-FUSION; VESICLES; HEMIFUSION AB For the act of membrane fusion, there are two competing, mutually exclusive molecular models that differ in the structure of the initial pore, the pathway for ionic continuity between formerly separated volumes. Because biological "fusion pores" can be as small as ionic channels or gap junctions, one model posits a proteinaceous initial fusion pore, Because biological fusion pore conductance varies widely, another model proposes a lipidic initial pore, We have found pore opening and flickering during the fusion of protein-free phospholipid vesicles with planar phospholipid bilayers, Fusion pore formation appears to follow the coalescence of contacting monolayers to create a zone of hemifusion where continuity between the two adherent membranes is lipidic, but not aqueous, Hypotonic stress, causing tension in the vesicle membrane, promotes complete fusion. Pores closed soon after opening (flickering), and the distribution of fusion pore conductance appears similar to the distribution of initial fusion pores in biological fusion, Because small flickering pores can form in the absence of protein, the existence of small pores in biological fusion cannot be an argument in support of models based on proteinaceous pores, Rather, these results support the model of a lipidic fusion pore developing within a hemifused contact site. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011 NR 43 TC 126 Z9 127 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14423 EP 14428 DI 10.1073/pnas.94.26.14423 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800038 PM 9405628 ER PT J AU Tagaya, Y Kurys, G Thies, TA Losi, JM Azimi, N Hanover, JA Bamford, RN Waldmann, TA AF Tagaya, Y Kurys, G Thies, TA Losi, JM Azimi, N Hanover, JA Bamford, RN Waldmann, TA TI Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE splice variant; posttranscriptional control ID ACTIVATED KILLER-CELLS; BETA-CHAIN; IL-2 RECEPTOR; GROWTH-FACTOR; PROLIFERATION; LYMPHOKINE; INDUCTION; CYTOKINE; CLONING AB Two isoforms of human interleukin 15 (IL-15) exist. One isoform has a shorter putative signal peptide (21 amino acids) and its transcript shows a tissue distribution pattern that is distinct from that of the alternative IL-15 isoform with a 48-aa signal peptide. The 21-aa signal isoform is preferentially expressed in tissues such as testis and thymus, Experiments using different combinations of signal peptides and mature proteins (IL-2, IL-15, and green fluorescent protein) showed that the short signal peptide regulates the fate of the mature protein by controlling the intracellular trafficking to nonendoplasmic reticulum sites, whereas the long signal peptide both regulates the rate of protein translation and functions as a secretory signal peptide. As a consequence, the IL-15 associated with the short signal peptide is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components, Such production of an intracellular lymphokine is not typical of other soluble interleukin systems, suggesting a biological function for IL-15 as an intracellular molecule. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Tagaya, Y (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 137 Z9 144 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14444 EP 14449 DI 10.1073/pnas.94.26.14444 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800042 PM 9405632 ER PT J AU Eckmann, L Rudolf, MT Ptasznik, A Schultz, C Jiang, T Wolfson, N Tsien, R Fierer, J Shears, SB Kagnoff, MF Traynor-Kaplan, AE AF Eckmann, L Rudolf, MT Ptasznik, A Schultz, C Jiang, T Wolfson, N Tsien, R Fierer, J Shears, SB Kagnoff, MF Traynor-Kaplan, AE TI D-myo-inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHLORIDE SECRETION; MAMMALIAN-CELLS; GROWTH-FACTOR; RAT-LIVER; CALCIUM; 3,4,5,6-TETRAKISPHOSPHATE; EXPRESSION; CHANNELS; BACTERIA; ENTRY AB Several inositol-containing compounds play key roles in receptor-mediated cell signaling events. Were, we describe a function for a specific inositol polyphosphate, D-myo-inositol 1,4,5,6-tetrakisphosphate [Ins(1,4,5,6)P-4], that is produced acutely in response to a receptor-independent process. Thus, infection of intestinal epithelial cells with the enteric pathogen Salmonella, but not with other invasive bacteria, induced a multifold increase in Ins(1,4,5,6)P-4 levels. To define a specific function of Ins(1,4,5,6)P-4, a membrane-permeant, hydrolyzable ester was used to deliver it to the intracellular compartment, where it antagonized epidermal growth factor (EGF)-induced inhibition of calcium-mediated chloride (Cl-) secretion (CaMCS) in intestinal epithelia. This EGF function is likely mediated through a phosphoinositide 3-kinase (PtdIns3K)-dependent mechanism because the EGF effects are abolished by wortmannin, and three different membrane-permeant esters of the PtdIns3K product phosphatidylinositol 3,4,5-trisphosphate mimicked the EGF effect on CaMCS. We further demonstrate that Ins(1,4,5,6)P-4 antagonized EGF signaling downstream of PtdIns3K because Ins(1,3,5,6)P-4 interfered with the PtdInsP(3) effect on CaMCS without affecting PtdIns3K activity. Thus, elevation of Ins(1,4,5,6)P-4 in Salmonella-infected epithelia may promote CI-flux by antagonizing EGF inhibition mediated through PtdIns3K and PtdInsP(3). C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Bremen, Inst Organ Chem, D-28359 Bremen, Germany. NIEHS, Signal Transduct Lab, Inositife Signaling Grp, Res Triangle Pk, NC 27709 USA. RP Traynor-Kaplan, AE (reprint author), Inolog Inc, 562 1st Ave S, Seattle, WA 98104 USA. OI Schultz, Carsten/0000-0002-5824-2171 NR 29 TC 73 Z9 75 U1 1 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 DEC 23 PY 1997 VL 94 IS 26 BP 14456 EP 14460 DI 10.1073/pnas.94.26.14456 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800044 PM 9405634 ER PT J AU Agostini, HT Yanagihara, R Davis, V Ryschkewitsch, CF Stoner, GL AF Agostini, HT Yanagihara, R Davis, V Ryschkewitsch, CF Stoner, GL TI Asian genotypes of JC virus in Native Americans and in a Pacific Island population: Markers of viral evolution and human migration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CEREBROSPINAL-FLUID; BRAIN; VARIANTS; URINE AB The human polyomavirus JC (JCV) causes the central nervous system demyelinating disease progressive multifocal leukoencephalopathy. Previously, we showed that 40% of Caucasians in the United States excrete JCV in the urine as detected by PCR, We have now studied 68 Navaho from New Mexico, 25 Flathead from Montana, and 29 Chamorro from Guam. By using PCR amplification of a fragment of the VP1 gene, JCV DNA was detected in the urine of 45 (66%) Navaho, 14 (56%) Flathead, and 20 (69%) Chamorro, Genotyping of viral DNAs in these cohorts by cycle sequencing showed predominantly type 2 (Asian), rather than type 1 (European), Type 1 is the major type in the United States and Hungary, Type 2 can be further subdivided into 2A, 2B, and 2C. Type 2A is found in China and Japan. Type 2B is a subtype related to the East Asian type, and is now found in Europe and the United States, The large majority (56-89%) of strains excreted by Native Americans and Pacific Islanders were the type 2A subtype, consistent with the origin of these strains in Asia, These findings indicate that JCV infection of Native Americans predates contact with Europeans, and likely predates migration of Amerind ancestors across the Bering land bridge around 12,000-30,000 years ago, If JCV had already differentiated into stable modern genotypes and subtypes prior to first settlement, the origin of JCV in humans may date from 50,000 to 100,000 years ago or more, We conclude that JCV may have coevolved with the human species, and that it provides a convenient marker for human migrations in both prehistoric and modern times. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Univ Hawaii Manoa, Pacific Biomed Res Ctr, Retroviral Res Lab, Honolulu, HI 96822 USA. Garden Wall Clin, St Ignatius, MT 59865 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-29, Bethesda, MD 20892 USA. NR 20 TC 128 Z9 132 U1 0 U2 9 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 DEC 23 PY 1997 VL 94 IS 26 BP 14542 EP 14546 DI 10.1073/pnas.94.26.14542 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800059 PM 9405649 ER PT J AU Puech, A Saint-Jore, B Funke, B Gilbert, DJ Sirotkin, H Copeland, NG Jenkins, NA Kucherlapati, R Morrow, B Skoultchi, AI AF Puech, A Saint-Jore, B Funke, B Gilbert, DJ Sirotkin, H Copeland, NG Jenkins, NA Kucherlapati, R Morrow, B Skoultchi, AI TI Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARDIO-FACIAL SYNDROME; CAT EYE SYNDROME; BALANCED TRANSLOCATION BREAKPOINT; EMBRYONIC STEM-CELLS; MOUSE GENOME; LINKAGE MAP; DIGEORGE-SYNDROME; LOCALIZATION; PROTEIN; LOCUS AB The region of human chromosome 22q11 is prone to rearrangements. The resulting chromosomal abnormalities are involved in Velo-cardio-facial and DiGeorge syndromes (VCFS and DGS) (deletions), "cat eye" syndrome (duplications), and certain types of tumors (translocations), As a prelude to the development of mouse models for VCFS/DGS by generating targeted deletions in the mouse genome, we examined the organization of genes from human chromosome 22q11 in the mouse, Using genetic linkage analysis and detailed physical mapping, we show that genes from a relatively small region of human 22q11 are distributed on three mouse chromosomes (MMU6, MMU10, and MMU16), Furthermore, although the region corresponding to about 2.5 megabases of the VCFS/DGS critical region is located on mouse chromosome 16, the relative organization of the region is quite different from that in humans, Our results show that the instability of the 22q11 region is not restricted to humans but may have been present throughout evolution, The results also underscore the importance of detailed comparative mapping of genes in mice and humans as a prerequisite for the development of mouse models of human diseases involving chromosomal rearrangements. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Skoultchi, AI (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI PUECH, Anne/A-7470-2013 FU NICHD NIH HHS [P01 HD34980-01] NR 60 TC 72 Z9 72 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14608 EP 14613 DI 10.1073/pnas.94.26.14608 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800070 PM 9405660 ER PT J AU Elmore, LW Hancock, AR Chang, SF Wang, XW Chang, S Callahan, CP Geller, DA Will, H Harris, CC AF Elmore, LW Hancock, AR Chang, SF Wang, XW Chang, S Callahan, CP Geller, DA Will, H Harris, CC TI Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tumor suppressor gene; hepatocarcinogenesis; programmed cell death; nitric oxide ID OXIDE SYNTHASE EXPRESSION; HEPATOCELLULAR-CARCINOMA; NITRIC-OXIDE; TRANSACTIVATION FUNCTION; DNA-BINDING; MUTATIONAL HOTSPOT; SURFACE-ANTIGEN; TRANSGENIC MICE; LIVER-CANCER; CELL-DEATH AB We have reported previously that the hepatitis B virus oncoprotein, HBx, can bind to the C terminus of p53 and inhibit several critical p53-mediated cellular processes, including DNA sequence-specific binding, transcriptional transactivation, and apoptosis. Recognizing the importance of p53-mediated apoptosis for maintaining homeostasis and preventing neoplastic transformation, here we further examine the physical interaction between HBx and p53 as well as the functional consequences of this association. In vitro binding studies indicate that the ayw and adr viral subtypes of HBx bind similar amounts of glutathione S-transferase-p53 with the distal C terminus of HBx (from residues 111 to 154) being critical for this interaction. Using a microinjection technique, we show that this same C-terminal region of HBx is necessary for sequestering p53 in the cytoplasm and abrogating p53-mediated apoptosis. The transcriptional transactivation domain of HBx also maps to its C terminus; however, a comparison of the ability of full-length and truncated HBx protein to abrogate p53-induced apoptosis versus transactivate simian virus 40- or human nitric oxide synthase-2 promoter-driven reporter constructs indicates that these two functional properties are distinct and thus may contribute to hepatocarcinogenesis differently. Collectively, our data indicate that the distal C-terminal domain of HBx, independent of its transactivation activity, complexes with p53 in the cytoplasm, partially preventing its nuclear entry and ability to induce apoptosis. These pathobiological effects of HBx may contribute to the early stages of hepatocellular carcinogenesis. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 58 TC 234 Z9 250 U1 1 U2 5 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 DEC 23 PY 1997 VL 94 IS 26 BP 14707 EP 14712 DI 10.1073/pnas.94.26.14707 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800087 PM 9405677 ER PT J AU Edinger, AL Mankowski, JL Doranz, BJ Margulies, BJ Lee, B Rucker, J Sharron, M Hoffman, TL Berson, JF Zink, MC Hirsch, VM Clements, JE Doms, RW AF Edinger, AL Mankowski, JL Doranz, BJ Margulies, BJ Lee, B Rucker, J Sharron, M Hoffman, TL Berson, JF Zink, MC Hirsch, VM Clements, JE Doms, RW TI CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MONONUCLEAR PHAGOCYTES; VACCINIA VIRUS; TYPE-1; HIV-1; AIDS; POLYMERASE; DEMENTIA; TROPISM; LINES AB Brain capillary endothelial cells (BCECs) are targets of CD4-independent infection by HIV-1 and simian immunodeficiency virus (SIV) strains in vitro and in vivo. Infection of BCECs may provide a portal of entry for the virus into the central nervous system and could disrupt blood-brain barrier function, contributing to the development of AIDS dementia. We found that rhesus macaque BCECs express chemokine receptors involved in HIV and SIV entry including CCR5, CCR3, CXCR4, and STRL33, but not CCR2b, GPR1, or GPR15. Infection of BCECs by the neurovirulent strain SIV/17E-Fr was completely inhibited by aminooxypentane regulation upon activation, normal T cell expression and secretion in the presence or absence of ligands, but not by eotaxin or antibodies to CD4. We found that the envelope (env) proteins from SIV/17E-Fr and several additional SIV strains mediated cell-cell fusion and virus infection with CD4-negative, CCR5-positive cells. In contrast, fusion with cells expressing the coreceptors STRL33, GPR1, and GPR15 was CD4-dependent. These results show that CCR5 can serve as a primary receptor for SIV in BCECs and suggest a possible CD4-independent mechanism for blood-brain barrier disruption and viral entry into the central nervous system. C1 Univ Penn, Dept Lab Med & Pathol, Philadelphia, PA 19104 USA. Johns Hopkins Sch Med, Div Comparat Med, Baltimore, MD 21205 USA. NIAID, NIH, Rockville, MD 20852 USA. RP Doms, RW (reprint author), Univ Penn, Dept Pathol, 806 Abramson,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. RI Lee, Benhur/A-8554-2016 OI Lee, Benhur/0000-0003-0760-1709 NR 36 TC 217 Z9 222 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 DEC 23 PY 1997 VL 94 IS 26 BP 14742 EP 14747 DI 10.1073/pnas.94.26.14742 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800093 PM 9405683 ER PT J AU Tessarollo, L Tsoulfas, P Donovan, MJ Palko, ME Blair-Flynn, J Hempstead, BL Parada, LF AF Tessarollo, L Tsoulfas, P Donovan, MJ Palko, ME Blair-Flynn, J Hempstead, BL Parada, LF TI Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DORSAL-ROOT-GANGLIA; TYROSINE KINASE RECEPTOR; SENSORY NEURONS; MESSENGER-RNAS; RAT TRKC; PROTEIN-KINASE; GROWTH-FACTOR; BDNF; EXPRESSION AB We have generated null mutant mice that lack expression of all isoforms encoded by the trkC locus. These mice display a behavioral phenotype characterized by a loss of proprioceptive neurons, Neuronal counts of sensory ganglia in the trkC mutant mice reveal less severe losses than those in NT-3 null mutant mice, strongly suggesting that NT-3, in vivo, may signal through receptors other than trkC. Mice lacking either NT-3 or all trkC receptor isoforms die in the early postnatal period. Histological examination of trkC-deficient mice reveals severe cardiac defects such as atrial and ventricular septal defects, and valvular defects including pulmonic stenosis, Formation of these structures during development is dependent on cardiac neural crest function, The similarities in cardiac defects observed in the trkC and NT-3 null mutant mice indicate that the trkC receptor mediates most NT-3 effects on the cardiac neural crest. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Neural Dev Grp, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Embryol Sect, Frederick, MD 21702 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Cornell Univ, Coll Med, Dept Med, New York, NY 10021 USA. RP Tessarollo, L (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Neural Dev Grp, POB B, Frederick, MD 21702 USA. RI Parada, luis/B-9400-2014 NR 58 TC 140 Z9 141 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14776 EP 14781 DI 10.1073/pnas.94.26.14776 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800099 PM 9405689 ER PT J AU Brustle, O Spiro, AC Karram, K Choudhary, K Okabe, S McKay, RDG AF Brustle, O Spiro, AC Karram, K Choudhary, K Okabe, S McKay, RDG TI In vitro-generated neural precursors participate in mammalian brain development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EMBRYONIC STEM-CELLS; IN-VITRO; CARCINOMA-CELLS; MOUSE EMBRYOS; NEURONS; DIFFERENTIATION; LINE; TERATOCARCINOMA; TRANSPLANTATION; MIGRATION AB During embryogenesis, pluripotent stem cells segregate into daughter lineages of progressively restricted developmental potential. In vitro, this process has been mimicked by the controlled differentiation of embryonic stem cells into neural precursors. To explore the developmental potential of these cell-culture-derived precursors in vivo, we have implanted them into the ventricles of embryonic rats. The transplanted cells formed intraventricular neuroepithelial structures and migrated in large numbers into the brain tissue. Embryonic-stem-cell-derived neurons, astrocytes, and oligodendrocytes incorporated into telencephalic, diencephalic, and mesencephalic regions and assumed phenotypes indistinguishable from neighboring host cells. These observations indicate that entirely in vitro-generated neural precursors are able to respond to environmental signals guiding cell migration and differentiation and have the potential to reconstitute neuronal and glial lineages in the central nervous system. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Brustle, O (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Room 5A29,36 Convent Dr, Bethesda, MD 20892 USA. NR 38 TC 228 Z9 239 U1 0 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 DEC 23 PY 1997 VL 94 IS 26 BP 14809 EP 14814 DI 10.1073/pnas.94.26.14809 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800105 PM 9405695 ER PT J AU Harper, JL Shin, YM Daly, JW AF Harper, JL Shin, YM Daly, JW TI Loperamide: A positive modulator for store-operated calcium channels? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thapsigargin; ATP; inositol trisphosphate; trifluoperazine; phorbol ester ID HUMAN ENDOTHELIAL-CELLS; CA2+ ENTRY; RAT; INHIBITION; BINDING; RELEASE; INFLUX; COLON AB The depletion of inositol trisphosphate-sensitive intracellular pools of calcium causes activation of store-operated calcium (SOC) channels. Loperamide at 10-30 mu M has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated. In HL-60 leukemic cells, the apparent positive modulatory effect of loperamide on SOC channels occurs when these channels have been activated after ATP, thapsigargin, or ionomycin-elicited depletion of calcium from intracellular storage sites. Loperamide has no effect when levels of intracellular calcium are elevated through a mechanism not involving SOC channels by using sphingosine. Loperamide caused augmentation of intracellular calcium levels after activation of SOC channels in NIH 3T3 fibroblasts, astrocytoma 1321N cells, smooth muscle DDT-MF2 cells, RBL-2H3 mast cells, and pituitary GH(4)C(1) cells. Only in astrocytoma cells did loperamide cause an elevation in intracellular calcium in the absence of activation of SOC channels. The augmentation of intracellular calcium elicited by loperamide in cultured cells was dependent on extracellular calcium and was somewhat resistant to agents (SKF 96365, miconazole, clotrimazole, nitrendipine, and trifluoperazine) that in the absence of loperamide effectively blocked SOC channels. It appears that loperamide augments influx of calcium through activated SOC channels. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8,Room 1A17, Bethesda, MD 20892 USA. RI Harper, Jacquie/A-8920-2014 NR 25 TC 24 Z9 24 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 1997 VL 94 IS 26 BP 14912 EP 14917 DI 10.1073/pnas.94.26.14912 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YN574 UT WOS:000071182800124 PM 9405713 ER PT J AU McEnery, MW Haase, H Vance, CL Dubel, SJ Morano, I Copeland, TD Choi, Y AF McEnery, MW Haase, H Vance, CL Dubel, SJ Morano, I Copeland, TD Choi, Y TI beta 1B subunit of voltage-dependent Ca2+ channels is predominant isoform expressed in human neuroblastoma cell line IMR32 SO FEBS LETTERS LA English DT Article DE calcium channel; beta subunit; differentiation; neuronal phenotype; neuroblastoma ID NERVE GROWTH-FACTOR; SENSITIVE CALCIUM-CHANNEL; SKELETAL-MUSCLE; FUNCTIONAL EXPRESSION; NEURITE OUTGROWTH; ALPHA-1 SUBUNIT; PC12 CELLS; BRAIN; RECEPTOR; CURRENTS AB Human neuroblastoma cells (IMR32) respond to treatment with either dibutyryl-cAMP or nerve factor by acquiring a neuronal phenotype which is accompanied by a marked increase in the density of neuronal (N-type) VDCC currents. Using IMR32 cells as a model for neuronal differentiation, we were interested in examining possible changes in the level of expression of the alpha 1B subunit of N-type calcium channels as well as beta subunit isoforms. Upon differentiation with dibutyryl-cAMP and 5-bromo-2-deoxyuridine for 16 days, ne observed a dramatic increase in alpha 1B protein which initiated between day 8 and 10. Day 10 evidenced maximal expression of alpha 1B protein, which was followed by an interval of relatively constant expression of alpha 1B (day 12 to day 16). Monitoring beta subunit expression using a pan specific anti-beta antibody (Ab CW20), we observed an increase in expression of a single 82 kDa beta subunit. The predominant 82 kDa beta subunit expressed throughout the course of differentiation was identified as the beta 1b isoform using a panel of beta subunit specific antibodies, Of significance, neither the beta 2 nor beta 3 isoforms were detected in full differentiated IMR32 cells, Contrary to a previous report on the absence of neurotypic expression of VDCC beta subunits in a second model for in vitro differentiation, NGF-treated rat pheochromocytoma cells (PC12 cells) [1], we report the regulated expression of the beta 1b protein in differentiated IMR32 cells suggesting a cell specific function for this beta subunit which parallels the acquisition of the neuronal phenotype. The restrictive expression of the beta 1b in IMR32 cells may reflect a cell-type specific function that extends beyond its role as an auxiliary subunit of VDCC complexes. (C) 1997 Federation of European Biochemical Societies. C1 Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP McEnery, MW (reprint author), Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM mwm4@po.cwru.edu NR 42 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 22 PY 1997 VL 420 IS 1 BP 74 EP 78 DI 10.1016/S0014-5793(97)01490-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YT250 UT WOS:000071580900016 PM 9450553 ER PT J AU Viswanathan, M Scalbert, E Delagrange, P Guardiola-Lemaitre, B Saavedra, JM AF Viswanathan, M Scalbert, E Delagrange, P Guardiola-Lemaitre, B Saavedra, JM TI Melatonin receptors mediate contraction of a rat cerebral artery SO NEUROREPORT LA English DT Article DE cerebral arteries; melatonin receptors; rat ID CAUDAL ARTERY; EXPRESSION; SYSTEM; BRAIN; YOUNG AB MELATONIN receptors are expressed in the cerebral arteries of the rat which form the circle of Willis. We report here that melatonin induces contraction of in vitro preparations of pressurized rat posterior communicating artery, in a concentration-dependent manner. This action of melatonin is inhibited by S-20928, a specific melatonin receptor antagonist. Our results demonstrate that the contractile action of melatonin is mediated by its receptors in the cerebral artery, and suggest a role for melatonin in the regulation of cerebral circulation. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. Inst Rech Int Servier, F-92415 Courbevoie, France. RP Viswanathan, M (reprint author), NIMH, Pharmacol Sect, Bldg 10,Room 2D-57,10 Ctr Dr,MSC 1514, Bethesda, MD 20892 USA. NR 14 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 22 PY 1997 VL 8 IS 18 BP 3847 EP 3849 DI 10.1097/00001756-199712220-00002 PG 3 WC Neurosciences SC Neurosciences & Neurology GA YN915 UT WOS:000071221500003 PM 9462453 ER PT J AU Schneider, TD AF Schneider, TD TI Information content of individual genetic sequences SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID DNA-BINDING SITES; ESCHERICHIA-COLI; REGULATORY PROTEINS; MOLECULAR MACHINES; NEURAL-NETWORK; SPLICE SITES; CONSENSUS SEQUENCES; NUCLEOTIDE-SEQUENCE; PROMOTER SEQUENCES; INITIATION SITES AB Related genetic sequences having a common function can be described by Shannon's information measure and depicted graphically by a sequence logo. Though useful for many purposes, sequence logos only show the average sequence conservation, and inferring the conservation for individual sequences is difficult. This limitation is overcome by the individual information (R-i) technique described here. The method begins by generating a weight matrix from the frequencies of each nucleotide or amino acid at each position of the aligned sequences. This matrix is then applied to the sequences themselves to determine the sequence conservation of each individual sequence. The matrix is unique because the average of these assignments is the total sequence conservation, and there is only one way to construct such a matrix. For binding sites on polynucleotides, the weight matrix has a natural cut-off that distinguishes functional sequences from other sequences. R-i values are on an absolute scale measured in bits of information so the conservation of different biological functions can be compared with one another. The matrix can be used to rank-order the sequences, to search for new sequences, to compare sequences to other quantitative data such as binding energy or distance between binding sites, to distinguish mutations from polymorphisms, to design sequences of a given strength, and to detect errors in databases. The Ri method has been used to identify previously undescribed but experimentally verified DNA binding sites. The individual information distribution was determined for E, coli ribosome binding sites, bacterial Fis binding sites, and human donor and acceptor splice junctions, among others. The distributions demonstrate clearly that the consensus sequence is highly unusual, and hence is a poor method to describe naturally occurring binding sites. C1 NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, POB B, Frederick, MD 21702 USA. EM toms@ncifcrf.gov OI Schneider, Thomas/0000-0002-9841-1531 NR 77 TC 202 Z9 205 U1 2 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD DEC 21 PY 1997 VL 189 IS 4 BP 427 EP 441 DI 10.1006/jtbi.1997.0540 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA YU770 UT WOS:000071752400008 PM 9446751 ER PT J AU Maestri, NE Beaty, TH Hetmanski, J Smith, EA McIntosh, I Wyszynski, DF Liang, KY Duffy, DL VanderKolk, C AF Maestri, NE Beaty, TH Hetmanski, J Smith, EA McIntosh, I Wyszynski, DF Liang, KY Duffy, DL VanderKolk, C TI Application of transmission disequilibrium tests to nonsyndromic oral clefts: Including candidate genes and environmental exposures in the models SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE linkage; birth defects; TGFA; TGFB3; smoking ID GROWTH-FACTOR-ALPHA; TRANSMISSION/DISEQUILIBRIUM TEST; MAJOR LOCUS; NO EVIDENCE; PALATE; LIP; LINKAGE; ASSOCIATION; TDT; INHERITANCE AB Extensive epidemiological and genetic studies of the cause of oral clefts have demonstrated strong familial aggregation but have failed to yield definitive evidence of any single genetic mechanism. We used the transmission/disequilibrium test (TDT) to investigate the relationship between oral clefts and markers associated with five candidate genes by utilizing 160 parent-offspring trios, Conditional logistic regression models extended the TDT to include covariates as effect modifiers, thus permitting tests for gene-environment interactions, For four of these candidates [transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), retinoic acid receptor (RARA), and the proto-oncogene BCL3], we detected modestly elevated odds ratios for the transmission of one marker allele to cleft probands when all the trios were analyzed together, These odds ratios increased when information on type of cleft, race, family history, or maternal smoking were incorporated as effect modifiers, We detected significant interaction between maternal smoking and the transmission of alleles for markers near TGFA and TGFB3; excess transmission of allele 3 at BCL3 was most significant among cleft lip probands; and the odds ratios for transmission of alleles at D19S178 and THRA1 were significant when ethnic group was included in the model, We suggest that utilizing an analytical strategy that allows for stratification of data and incorporating environmental effects into a single analysis may be more effective for detecting genes of small effect. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,CTR GENET MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD. QUEENSLAND INST MED RES,EPIDEMIOL & POPULAT HLTH UNIT,BRISBANE,QLD 4006,AUSTRALIA. RI Liang, Kung-Yee/F-8299-2011; Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X FU NIDCR NIH HHS [R01-DE10293] NR 41 TC 107 Z9 114 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 19 PY 1997 VL 73 IS 3 BP 337 EP 344 DI 10.1002/(SICI)1096-8628(19971219)73:3<337::AID-AJMG21>3.0.CO;2-J PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YH577 UT WOS:A1997YH57700021 PM 9415696 ER PT J AU Nawashiro, H Martin, D Hallenbeck, JM AF Nawashiro, H Martin, D Hallenbeck, JM TI Neuroprotective effects of TNF binding protein in focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE tumor necrosis factor; TNF binding protein; brain infarction; mouse; DNA fragmentation ID TUMOR-NECROSIS-FACTOR; MANGANESE-SUPEROXIDE-DISMUTASE; FACTOR-ALPHA; ARTERY OCCLUSION; INFARCT VOLUME; BRAIN; RATS; EXPRESSION; LIPOPOLYSACCHARIDE; MECHANISM AB The effect of tumor necrosis factor binding protein (TFNbp) was studied in mice subjected to a permanent middle cerebral artery occlusion (MCAO). TNFbp is a dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp), and binds and inhibits TNF-alpha. TNFbp produced a significant reduction in the cortical infarct volume (22.6 +/- 3.5 mm(3) immediately after MCAO; 25.2 +/- 2.4 mm(3) 1 h after MCAO) compared with vehicle-treated animals (30.3 +/- 3.7 mm(3) immediately post MCAO; 31 +/- 3.7 mm(3) 1 h after MCAO (mean +/- S.D.) when administered intracranially up to 60 min post-occlusion. The neuroprotective effect of TNFbp was sustained in mice for 2 weeks after MCAO. DNA fragmentation at the margin of the cortical infarcts was dramatically reduced in mice treated with TNFbp whereas all control animals showed consistent and obvious DNA fragmentation 2 weeks after MCAO. TNFbp could have therapeutic value for the treatment of ischemic stroke if the problem of delivery to brain can be overcome. (C) 1997 Elsevier Science B.V. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Amgen Inc, Dept Pharmacol, Boulder, CO USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4A03,36 Covent Dr MSC 4128, Bethesda, MD 20892 USA. NR 23 TC 104 Z9 109 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 19 PY 1997 VL 778 IS 2 BP 265 EP 271 DI 10.1016/S0006-8993(97)00981-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YP262 UT WOS:000071259300002 PM 9459543 ER PT J AU Bengel, D Johren, O Andrews, AM Heils, A Mossner, R Sanvitto, GL Saavedra, JM Lesch, KP Murphy, DL AF Bengel, D Johren, O Andrews, AM Heils, A Mossner, R Sanvitto, GL Saavedra, JM Lesch, KP Murphy, DL TI Cellular localization and expression of the serotonin transporter in mouse brain SO BRAIN RESEARCH LA English DT Article DE serotonin transporter; raphe nuclei; gene expression; In situ hybridization; [I-125]RTI-55 binding; mice ID ANTIDEPRESSANT BINDING-SITES; DORSAL RAPHE NUCLEUS; MESSENGER-RNA; RAT-BRAIN; H-3 PAROXETINE; NEUROTRANSMITTER TRANSPORTERS; QUANTITATIVE AUTORADIOGRAPHY; MICE; RECEPTORS; CLONING AB The high-affinity serotonin (5-HT) transporter (5-HTT) plays an important role in the removal of extracellular serotonin, thereby modulating and terminating the action of this neurotransmitter at various pre-and post-synaptic serotonergic receptors and heteroreceptors. In order to characterize the anatomical distribution of the 5-HTT in mouse brain, in situ hybridization histochemistry using ?S-35-labeled riboprobes was performed. These results were compared with 5-HTT binding site distribution as evaluated by [I-125]RTI-55 autoradiography. High levels of 5-HTT mRNA were detected in all brain stem raphe nuclei, with variations in labeling among the various subnuclei. Those bl ain arena known; to possess serotonergic cell bodies stained intensely for both 5-HTT mRNA and 5-HTT binding sites. In contrast to previous findings in rat brain, the highest densities of 5-HTT sites were found in areas outside the raphe complex, particularly in the substantia nigra, globus pallidus, and superior colliculi. (C) 1997 Elsevier Science B.V. C1 NIMH, Clin Sci Lab, Sect Clin Neuropharmacol, NIH,Clin Ctr, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Pharmacol Sect, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. RP Bengel, D (reprint author), NIMH, Clin Sci Lab, Sect Clin Neuropharmacol, NIH,Clin Ctr, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. RI Johren, Olaf/G-6967-2011; Andrews, Anne/B-4442-2011; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X NR 49 TC 43 Z9 43 U1 2 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 DEC 19 PY 1997 VL 778 IS 2 BP 338 EP 345 DI 10.1016/S0006-8993(97)01080-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YP262 UT WOS:000071259300010 PM 9459551 ER PT J AU Shi, CS Kehrl, JH AF Shi, CS Kehrl, JH TI Activation of stress-activated protein kinase c-Jun N-terminal kinase, but not NF-kappa B, by the tumor necrosis factor (TNF) receptor 1 through a TNF receptor-associated factor 2- and germinal center kinase related-dependent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMAIN; PHOSPHORYLATION; IDENTIFICATION; APOPTOSIS; CASCADE; DEATH; LIGHT; ERK AB A key step by which tumor necrosis factor (TNF) signals the activation of nuclear factor-kappa B (NF-kappa B) and the stress-activated protein kinase (SAPK, also called c-Jun N-terminal kinase or JNK) is the recruitment to the TNF receptor of TNF receptor-associated factor 2 (TRAF2). However, the subsequent steps in TRAF2-induced SAPK and NF-kappa B activation remain unresolved. Here we report the identification of a TNF-responsive serine/threonine protein kinase termed GCK related (GCKR) that likely signals via mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase kinase 1 (MEKK1) to activate the SAPK pathway. TNF, TRAF2, and ultraviolet (UV) light, which in part uses the TNF receptor signaling pathway, all increased GCKR activity. A TRAF2 mutant, which inhibits both TRAF2-induced NF-kappa B and SAPK activation, blocked TNF-induced GCKR activation. Finally, interference with GCKR expression impeded TRAF2- and TNF-induced SAPK activation but not that of NF-kappa B. This suggests a divergence in the TNF signaling pathway that leads to SAPK and NF-kappa B activation, which is located downstream of TRAF2 but upstream of GCKR. C1 NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, Bldg 10,Rm 11B-13,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. NR 34 TC 93 Z9 95 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32102 EP 32107 DI 10.1074/jbc.272.51.32102 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000026 PM 9405407 ER PT J AU Caterina, NCM Windsor, LJ Yermovsky, AE Bodden, MK Taylor, KB Birkedal-Hansen, H Engler, JA AF Caterina, NCM Windsor, LJ Yermovsky, AE Bodden, MK Taylor, KB Birkedal-Hansen, H Engler, JA TI Replacement of conserved cysteines in human tissue inhibitor of metalloproteinases-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASES; HUMAN-FIBROBLASTS; PLASMID DNA; COLLAGENASE INHIBITORS; DIRECTED MUTAGENESIS; TERMINAL DOMAIN; EXPRESSION; TIMP; GELATINASE; GROWTH AB Tissue inhibitor of metalloproteinases-l (TIMP-1) is resistant to extremes of temperature and pH, This is thought to be due in part to the presence of six sulfhydryl bridges presumed to maintain the structural integrity of the molecule, As part of a study looking at structure-function relationships, a number of the conserved cysteine residues in TIMP-1 were targeted for replacement: with serine, Single and double replacements of these conserved cysteines, as well as replacements around these cysteines, were expressed using a vaccinia virus system and analyzed for functional and structural competence, Analysis by circular dichroism indicated that these mutants maintained secondary structures similar to those of mild-type TIMP-1. Trypsin susceptibility experiments indicated that the tertiary structure of the mutants had not been drastically changed, Analysis of functional competence demonstrated that there were significant changes in some of these mutants, Assays using collagen fibrils or gelatin as substrates indicated that the double mutant C1S/C70S, but not C3S/C99S, had lost inhibitory activity against human fibroblast-type collagenase (FIB-CL) and at high concentrations only had slight activity against M-r 72,000 gelatinase (M-r 72,000 gelatinase). Kinetic analysis of TIMP-1 inhibition of FIB-CL cleavage of a peptide substrate indicated that mutants C1S/C70S, C3S/C99S, and CEEC --> CQQC retained their ability to inhibit FIB-CL in a manner similar to wild-type TIMP-1, while mutants C1S and C70S showed little inhibitory activity, The mutants C99S and C137S could also inhibit FIB-CL cleavage of the peptide substrate, The results indicated that the degree of inhibition by the TIMP-1 mutants varied somewhat depending on the choice of substrates, interestingly replacing both cysteines from a disulfide bond in the wild-type molecule resulted in a more competent inhibitor than either of the single site "parent" mutations, Taken together, these experiments indicate that TIMP-1 can be rendered inactive by the loss of a single cysteine. C1 Univ Alabama, Dept Biochem & Mol Genet, Sch Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Dent, Dept Oral Biol, Birmingham, AL 35294 USA. Univ Alabama, Sch Dent, Dept Restorat Dent, Birmingham, AL 35294 USA. Univ Alabama, Oral Biol Res Ctr, Birmingham, AL 35294 USA. NIDR, NIH, Bethesda, MD 20892 USA. RP Engler, JA (reprint author), Univ Alabama, Dept Biochem & Mol Genet, Sch Med, Birmingham, AL 35294 USA. FU NIDCR NIH HHS [DE08228, DE00283, DE10631] NR 46 TC 24 Z9 26 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32141 EP 32149 DI 10.1074/jbc.272.51.32141 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000032 PM 9405413 ER PT J AU Nomizu, M Kuratomi, Y Song, SY Ponce, ML Hoffman, MP Powell, SK Miyoshi, K Otaka, A Kleinman, HK Yamada, Y AF Nomizu, M Kuratomi, Y Song, SY Ponce, ML Hoffman, MP Powell, SK Miyoshi, K Otaka, A Kleinman, HK Yamada, Y TI Identification of cell binding sequences in mouse laminin gamma 1 chain by systematic peptide screening SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OUTGROWTH-PROMOTING DOMAIN; CAPILLARY-LIKE STRUCTURES; TERMINAL GLOBULAR DOMAIN; HUMAN-ENDOTHELIAL CELLS; AMINO-ACID-SEQUENCE; EGF-LIKE MOTIF; NEURITE OUTGROWTH; B2 CHAIN; SYNTHETIC PEPTIDES; BASEMENT-MEMBRANE AB Laminin-1, a major component of basement membranes, consists of three different chains designated alpha 1, beta 1, and gamma 1 and has diverse biological functions. We have identified cell binding sites on the mouse laminin gamma 1 chain, using systematic screening of 165 overlapping synthetic peptides covering the entire chain. We identified 12 cell binding sequences using HT-1080 human fibrosarcoma and B16-F10 mouse melanoma cells in two independent assays employing peptide-conjugated Sepharose beads and peptide-coated dishes. Four peptides (C-16, C-28, C-64, and C-68) located on the globular domains of the gamma 1 chain were the most active and showed dose-dependent cell attachment. Cell attachment to C-68 was inhibited by EDTA and by anti-alpha(2) beta(1) integrin antibodies. Cell attachment to C-16 and C-64 was partially inhibited by EDTA but was not inhibited by anti-integrin antibodies. EDTA and anti-integrin antibodies did not affect cell attachment to C-28. The four peptides were tested in adhesion and differentiation assays with endothelial, neuronal, and human salivary gland cells. C-16 was the most active for all of the cells, whereas the other three peptides showed cell type specificity in their activities. The active core sequences of C-16, C-28, C-64, and C-68 are YVRL, IRVTLN, TTVKYIFR, and SIKIRGTY, respectively. These sequences are highly conserved among the different species and in the laminin gamma 2 chain. These results suggest that the specific sequences on the laminin gamma 1 chain are biologically active and interact with distinct cell surface receptors. C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Fac Pharmaceut Sci, Sakyo Ku, Kyoto 606, Japan. RP Yamada, Y (reprint author), NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg30,Rm 405, Bethesda, MD 20892 USA. NR 46 TC 88 Z9 89 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32198 EP 32205 DI 10.1074/jbc.272.51.32198 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000040 PM 9405421 ER PT J AU Liu, C Shen, K Liu, ZY Noguchi, CT AF Liu, C Shen, K Liu, ZY Noguchi, CT TI Regulated human erythropoietin receptor expression in mouse brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL-CELLS; GENE-EXPRESSION; TRANSGENIC MICE; MESSENGER-RNA; ERYTHROID-CELLS; NERVOUS-SYSTEM; TRANSCRIPTION; DIFFERENTIATION; PROLIFERATION; HEMATOPOIESIS AB Erythropoietin (Epo) is known for its role in erythropoiesis and acts by binding to its receptor (EpoR) on the surface of erythroid progenitors, EpoR activity follows the site of hematopoiesis from the embryonic yolk sac to the fetal liver and then the adult spleen and bone marrow, Expression of EpoR has also been observed in selected cells of non-hematopoietic origin, such as the embryonic mouse brain during mid-gestation, at levels comparable to adult bone marrow, EpoR transcripts in brain decrease during development falling by birth to less than 1-3% of the level in hematopoietic tissue, We have now recapitulated this pattern of expression using a human EpoR transgene consisting of an 80-kb human EpoR genomic fragment. The highest level of expression was observed in the embryonic yolk sac and fetal liver, analogous to the endogenous gene, in addition to ex- pression in adult spleen and bone marrow, Although activity of this transgene in brain is initially lower than the endogenous gene, it does exhibit the down-regulation observed for the endogenous gene in adult brain, The expression pattern of hybrid transgenes of an hEpoR promoter fused to beta-galactosidase in 9.5-day embryos suggested that the hEpoR promoter region between -1778 and -150 bp 5' of the transcription start site is necessary to direct EpoR expression in the neural tube, EpoR expression in the neural tube may be the origin of the EpoR transcripts detected in brain during development, These data demonstrate that both the mouse and human EpoR genes contain regulatory elements to direct significant levels of expression in a developmentally controlled manner in brain and suggest that in addition to its function during erythropoiesis, EpoR may play a role in the development of selected non-hematopoietic tissue. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 42 TC 102 Z9 107 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32395 EP 32400 DI 10.1074/jbc.272.51.32395 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000067 PM 9405448 ER PT J AU Bortner, CD Hughes, FM Cidlowski, JA AF Bortner, CD Hughes, FM Cidlowski, JA TI A primary role for K+ and Na+ efflux in the activation of apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; VOLUME; FAS; THYMOCYTES AB Cell shrinkage is a major characteristic of apoptosis, but the mechanism and role of this process in cell death are poorly understood. The primary factor that controls volume regulation in all cells is ions, and thus we have examined the movement of ions at the single cell level in lymphocytes during apoptosis, Activation of the death program with several stimuli that act through independent pathways to stimulate apoptosis results in a synchronous shift of cells from a normal cell size to a shrunken cell size. Only the shrunken cells exhibit DNA fragmentation and an approximate 4-fold elevation of caspase-3-like activity. Analysis of K+ and Na+ ion content of individual cells by flow cytometry revealed that the intracellular ionic strength of apoptotic cells decreased substantially from their non-shrunken counterparts. Additionally, we show apoptosis is enhanced under conditions where the intracellular K+ concentration is diminished and that apoptosis is inhibited when K+ efflux is prevented. These data show that the efflux of ions, primarily potassium, plays a necessary and perhaps a pivotal role in the cell death program. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 414 Z9 424 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32436 EP 32442 DI 10.1074/jbc.272.51.32436 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000072 PM 9405453 ER PT J AU Okazaki, H Zhang, J Hamawy, MM Siraganian, RP AF Okazaki, H Zhang, J Hamawy, MM Siraganian, RP TI Activation of protein-tyrosine kinase Pyk2 is downstream of Syk in Fc epsilon RI signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; LEUKEMIA RBL-2H3 CELLS; FOCAL ADHESION KINASE; TUMOR MAST-CELLS; IMMUNOGLOBULIN-E; CROSS-LINKING; PHOSPHOLIPASE C-GAMMA-1; HISTAMINE-RELEASE; PHOSPHORYLATION; TRANSDUCTION AB Aggregation of the Fc epsilon RI, a member of the immune receptor family, induces the activation of protein-tyrosine kinases and results in tyrosine phosphorylation of proteins that are involved in downstream signaling pathways. Here we report that Pyk2, another member of the focal adhesion kinase family, was present in the RBL-2H3 mast cell line and was rapidly tyrosine-phosphorylated and activated after Fc epsilon RI aggregation. Tyrosine phosphorylation of Pyk2 was also induced by the calcium ionophore A23187, by phorbol myristate acetate, or by stimulation of G-protein-coupled receptors. Adherence of cells to fibronectin dramatically enhanced the induced tyrosine phosphorylation of Pyk2. Although Src family kinases are activated by Fc epsilon RI stimulation and tyrosine-phosphorylate the receptor subunits, the activation and tyrosine phosphorylation of Pyk2 were downstream of Syk. In contrast, tyrosine phosphorylation of Pyk2 by stimulation of G-protein-coupled receptors was independent of Syk. Therefore, the Fc epsilon RI-induced tyrosine phosphorylation of Pyk2 is downstream of Syk and may play a role in cell secretion. C1 NIDR, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Okazaki, H (reprint author), NIDR, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bldg 10,Rm 1N106, Bethesda, MD 20892 USA. NR 49 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32443 EP 32447 DI 10.1074/jbc.272.51.32443 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000073 PM 9405454 ER PT J AU Iwata, T Minucci, S McGowan, M Carper, D AF Iwata, T Minucci, S McGowan, M Carper, D TI Identification of a novel cis-element required for the constitutive activity and osmotic response of the rat aldose reductase promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE; TRANSCRIPTION; INVIVO; CELLS; EXPRESSION; PROTEIN; STRESS AB A new and essential cis-element AEE (aldose reductase enhancer element), necessary for the constitutive activity and the osmotic stress response of rat aldose reductase transcription in a rat liver cell line, has been identified. In transient transfection assays, an increase in promoter activity, up to 3.8-fold, was observed with osmotic stress (600 mosm/kg H2O) using a luciferase reporter gene construct containing aldose reductase promoter sequence from -1,094 base pair (bp) to +23 bp. A deletion between -1,071 and -895 bp reduced the constitutive activity and abolished the osmotic response of the promoter. Exonuclease III mediated in vivo DNA footprinting and dimethyl sulfate in vivo footprinting revealed DNA protection of a 32-bp region and two guanosines (G) within this region protected from methylation, respectively. Electrophoretic gel mobility shift assays using whole liver cell extracts showed protein binding, under both normal and stressed conditions. Deletion of the sequence between the two guanosines protected by in vivo dimethyl sulfate DNA footprinting (GAAGAGTG) in a luciferase construct (-1,094 bp to +23 bp) abolished the constitutive promoter activity. One copy of AEE fused to the thymidine kinase promoter gave a maximum constitutive activity of 7.7-fold and a maximum osmotic response activity of 6.7-fold. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Carper, D (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, 9000 Rockville Pike,Bldg 6,Rm 232, Bethesda, MD 20892 USA. RI Minucci, Saverio/J-9669-2012 NR 23 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32500 EP 32506 DI 10.1074/jbc.272.51.32500 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000080 PM 9405461 ER PT J AU Joe, YA Wolff, EC Lee, YB Park, MH AF Joe, YA Wolff, EC Lee, YB Park, MH TI Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis - The role of Lys(329) in human deoxyhypusine synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; FUNCTIONAL EXPRESSION; HYPUSINE DEPLETION; MOLECULAR-CLONING; CELL VIABILITY; INHIBITION; GENE; INITIATION; CDNA; IDENTIFICATION AB Deoxyhypusine synthase catalyzes the first step in the post-translational synthesis of hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A. We recently reported biochemical evidence for a covalent enzyme-substrate intermediate involving a specific lysine residue (Lys(329)) in human deoxyhypusine synthase (Wolff, E. C., Polk, J. E., and Park, M. H. (1997) J. Biol. Chem. 272, 15865-15871), In an effort to evaluate the role of this enzyme-substrate intermediate in catalysis, we carried out site-directed mutagenesis (Lys to Arg and/or Ala) of the conserved lysine residues in human deoxyhypusine synthase. A drastic reduction in enzyme intermediate formation and enzymatic activities was observed with mutant proteins with substitution at Lys(287) but, not with those with mutations at residues 141, 156, 205, 212, 226, 251, or 338. Lys to Ala or Lys to Arg substitution at Lys(329) totally abolished covalent enzyme-substrate intermediate formation and deoxyhypusine synthesis activity, indicating that Lys(329) is the unique site for the enzyme intermediate and that it is absolutely required for deoxyhypusine synthesis in the eukaryotic translation initiation factor 5A precursor. The K329A mutant showed spermidine cleavage activity (similar to 6% of the wild type enzyme) suggesting that in contrast to deoxyhypusine synthesis, spermidine cleavage can occur without enzyme intermediate formation. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Park, MH (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Rm 211, Bethesda, MD 20892 USA. NR 27 TC 14 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 1997 VL 272 IS 51 BP 32679 EP 32685 DI 10.1074/jbc.272.51.32679 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YM852 UT WOS:000071108000105 PM 9405486 ER PT J AU Janini, GM Issaq, HJ Muschik, GM AF Janini, GM Issaq, HJ Muschik, GM TI Electrokinetic chromatography without electroosmotic flow SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE reviews; electrokinetic chromatography, reversed-flow; pseudo-stationary phases; enantiomer separation; positional isomers; partition coefficients; coated columns; hydrophobic solutes; cyclodextrins ID CAPILLARY ZONE ELECTROPHORESIS; OPEN-TUBULAR CAPILLARIES; HOST-GUEST COMPLEXATION; ETHER-BETA-CYCLODEXTRIN; CHIRAL SEPARATIONS; MICELLAR SOLUTIONS; LIQUID-CHROMATOGRAPHY; ENANTIOMERIC SEPARATION; PARTITION-COEFFICIENT; ANIONIC CYCLODEXTRINS AB This review summarizes the various aspects of conducting electrokinetic chromatography in coated columns with suppressed electroosmotic flow. The specific features of the technique will be presented and the potential applications explored. The equations of migration, resolution and zone spreading for neutral solutes will be presented, compared, and contrasted with those of conventional electrokinetic chromatography in bare-silica columns. The principle of separation is the same in electrokinetic chromatography with or without electroosmotic flow; however, there are many significant differences that will be highlighted. Published by Elsevier Science B.V. C1 NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 66 TC 35 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 19 PY 1997 VL 792 IS 1-2 BP 125 EP 141 DI 10.1016/S0021-9673(97)00882-0 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YT286 UT WOS:000071584900012 PM 9463907 ER PT J AU Kaplan, B Yakar, S Balta, Y Pras, M Martin, B AF Kaplan, B Yakar, S Balta, Y Pras, M Martin, B TI Isolation and purification of two major serum amyloid A isotypes SAA1 and SAA2 from the acute phase plasma of mice SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE serum amyloid A isotypes; high-density-lipoprotein apoproteins ID A GENE FAMILY; PROTEIN SAA; MOUSE; EXPRESSION; CHROMATOGRAPHY; HETEROGENEITY; DEPOSITION; SEQUENCES; CLEAVAGE; ISOFORMS AB A new procedure was developed fur isolation of two major serum amyloid A (SAA) isotypes SAA1 and SAA2 from acute-phase plasma of mice. The procedure included preparation of high-density lipoproteins (HDLs) and their separation by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The SAA proteins (M-r 12 000) were electroeluted and afterwards purified from SDS by gel permeation chromatography on a Fractogel TSK-40F column in aqueous 50% acetonitrile-0.1% TFA. Finally, the SAA proteins free from SDS were fractionated by high-performance liquid chromatography on a Vydac 214TP54 column (250X4.6 mm I.D., particle size 5 mu m), yielding two major fractions with k=5.2 and k=5.5. The N- and C-terminal sequence analyses and mass spectrometry demonstrated the purity of these two major fractions and their identity with apo SAA1 (k=5.2) and apo SAA2 (k=5.5). The developed procedure is applicable to small amounts of pooled murine plasma (6-7 ml) and could be readily modified from small to large scale preparations. (C) 1997 Elsevier Science B.V. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NIH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Kaplan, B (reprint author), Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NR 32 TC 11 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 19 PY 1997 VL 704 IS 1-2 BP 69 EP 76 DI 10.1016/S0378-4347(97)00462-3 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YQ889 UT WOS:000071434600009 PM 9518179 ER PT J AU Roth, T Morningstar, ML Boyer, PL Hughes, SH Buckheit, RW Michejda, CJ AF Roth, T Morningstar, ML Boyer, PL Hughes, SH Buckheit, RW Michejda, CJ TI Synthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-aryl-substituted benzimidazoles SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; 1H,3H-THIAZOLO<3,4-A>BENZIMIDAZOLES; THIAZOLOBENZIMIDAZOLE; RESISTANCE; AGENTS AB The development of new nonnucleoside inhibitors of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) active against the drug-induced mutations in RT continues to be a very important goal of AIDS research. We used a known inhibitor of HIV-1 RT, 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TZB), as the lead structure for drug design with the objective of making more potent inhibitors against both wild-type (WT) and variant RTs. A series of structurally related 1,2-substituted benzimidazoles was synthesized and evaluated for their ability to inhibit in vitro polymerization by HIV-1 WT RT. A structure- activity study was carried out for the series of compounds to determine the optimum groups; for substitution of the benzimidazole ring at the N1 and C2 positions. The best inhibitor, 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimidazole (35), has an IC50 = 200 nM against HIV-1 WT RT in an in vitro enzyme assay. Cytoprotection assays utilizing HIV-infected MT-4 cells revealed that 35 had strong antiviral activity (EC50 = 440 nM) against wild-type virus while retaining broad activity;against many clinically observed HIV-1 strains resistant to nonnucleoside inhibitors. Overall, the activity of 35 against wild-type and resistant strains with amino acid substitution in RT is 4-fold or greater than that of TZB and is comparable to that of other nonnucleoside inhibitors currently undergoing clinical trials, most of which do not have the capacity to inhibit the variant forms of the enzyme. C1 NCI, Mol Aspects Drug Design Sect, ABL Basic Res & Dev Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Gene Express Eukaryotes Sect, ABL Basic Res & Dev Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Frederick Res Ctr, So Res Inst, Frederick, MD 21701 USA. RP Michejda, CJ (reprint author), NCI, Mol Aspects Drug Design Sect, ABL Basic Res & Dev Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 25 TC 266 Z9 272 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 19 PY 1997 VL 40 IS 26 BP 4199 EP 4207 DI 10.1021/jm970096g PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YQ059 UT WOS:000071343300003 PM 9435891 ER PT J AU Agoston, GE Wu, JH Izenwasser, S George, C Katz, J Kline, RH Newman, AH AF Agoston, GE Wu, JH Izenwasser, S George, C Katz, J Kline, RH Newman, AH TI Novel N-substituted 3 alpha-[bis(4 '-fluorophenyl)methoxy]tropane analogues: Selective ligands for the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; UPTAKE INHIBITORS; SEROTONIN UPTAKE; RAT-BRAIN; COCAINE; BINDING; POTENT; NORADRENALINE; SITES; DRUGS AB A series of N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues has been prepared that function as dopamine uptake inhibitors. The N-methylated analogue of this series had a significantly higher affinity for the dopamine transporter than the parent compound, N-methyl-3 alpha-(diphenylmethoxy)tropane (benztropine, Cogentin). Yet like the parent compound, it retained high affinity for muscarinic receptors. A series of N-substituted compounds were prepared from nor-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane via acylation followed by hydride reduction of the amide or by direct alkylation. All compounds containing a basic tropane nitrogen displaced [H-3]WIN 35,428 at the dopamine transporter (K-i range = 8.5-634 nM) and blocked dopamine uptake (IC50 range = 10-371 nM) in rat caudate putamen, whereas ligands with a nonbasic nitrogen were virtually inactive. None of the compounds demonstrated high binding affinity at norepinephrine or serotonin transporters. Importantly, a separation of binding affinities for the dopamine transporter versus muscarinic m(i) receptors was achieved by substitution of the N-methyl group with other N-alkyl or arylalkyl substituents (eg. n-butyl, allyl, benzyl, 3-phenylpropyl, etc.). Additionally, the most potent and selective analogue in this series at the dopamine transporter, N-(4 "-phenyl-n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane analogue failed to substitute for cocaine in rats trained to discriminate cocaine from saline. Potentially, new leads toward the development of a pharmacotherapeutic for cocaine abuse and other disorders affecting the dopamine transporter may be discovered. C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Newman, AH (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA09045] NR 28 TC 81 Z9 82 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 19 PY 1997 VL 40 IS 26 BP 4329 EP 4339 DI 10.1021/jm970525a PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YQ059 UT WOS:000071343300014 PM 9435902 ER PT J AU Husbands, SM Izenwasser, S Loeloff, RJ Katz, JL Bowen, WD Vilner, BJ Newman, AH AF Husbands, SM Izenwasser, S Loeloff, RJ Katz, JL Bowen, WD Vilner, BJ Newman, AH TI Isothiocyanate derivatives of 9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]-carbazole (rimcazole): Irreversible ligands for the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT CAUDATE-PUTAMEN; SIGMA-RECEPTORS; H-3 (+)-PENTAZOCINE; COCAINE; BINDING; POTENT; GBR-12909 AB Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [H-3]WIN 35,428 in tissue that had been preincubated with the Ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in B-max was accompanied by a concentration-related decrease in K-D values. This shift in K-D to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [H-3]WIN 35,428 site on the dopamine transporter. These Ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment. C1 NIDA, Psychobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA. NIDDK, Med Chem Lab, Bethesda, MD 20892 USA. RP NIDA, Psychobiol Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011; Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159; Husbands, Stephen/0000-0002-9928-6322 NR 24 TC 23 Z9 24 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD DEC 19 PY 1997 VL 40 IS 26 BP 4340 EP 4346 DI 10.1021/jm9705519 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YQ059 UT WOS:000071343300015 PM 9435903 ER PT J AU Lomenzo, SA Izenwasser, S Katz, JL Terry, PD Zhu, NJ Klein, CL Trudell, ML AF Lomenzo, SA Izenwasser, S Katz, JL Terry, PD Zhu, NJ Klein, CL Trudell, ML TI Synthesis, structure, dopamine transporter affinity, and dopamine uptake inhibition of 6-alkyl-3-benzyl-2-[(methoxycarbonyl)methyl]tropane derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECEPTOR; LIGAND-BINDING; ANALOGS; (+)-FERRUGININE; DISCOVERY; ALKALOIDS; TROPANES; POTENT; SITES; ESTER AB A series of 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter(DAT). The in vitro affinity (K-i) for the DAT of the 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues was determined by inhibition of [H-3]WIN 35,428 in rat-caudate putamen tissue. The inhibition of dopamine uptake (IC50) was also measured for selected compounds which demonstrated moderate affinity for the dopamine transporter. The unsubstituted enantiopure analogues (-)-190 (K-i = 33 nM) and surprisingly (+)-20a (K-i = 60 nM) were found to be almost equipotent with the high-affinity binding components of cocaine and WIN 35,065-2 and exhibited slightly more potent dopamine uptake inhibition than both cocaine and WIN 35,065-2. In general, substitution at the 6-position of racemic 19a and 200 with alkyl groups was found to result in decreased activity relative to increased chain length of the substituent. The 3 beta-benzyl-2 beta-[(methoxycarbonyl)methyl]-6 beta-methyltropane (21b; K-i = 57 nM) was the only 6-alkyl derivative to exhibit moderately potent activity. The 6 beta-isomer 21b was 4-fold more potent than the 6 alpha-isomer 19b (K-i = 211 nM) and was nearly equipotent with (-)-19a and (+)-20a as well as with cocaine and WIN 35,065-2. The results of this study further demonstrate the steric constraints associated with the C(6)-C(7) methylene bridge of the tropane ring system for molecular recognition of cocaine analogues at the cocaine binding site(s) on the DAT. C1 Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. NIDA, Div Intramural Res, Baltimore, MD 21224 USA. Xavier Univ, Dept Chem, New Orleans, LA 70125 USA. RP Trudell, ML (reprint author), Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. EM mltcm@uno.edu RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [R29 DA08055, F31 DA05742] NR 44 TC 28 Z9 28 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 19 PY 1997 VL 40 IS 26 BP 4406 EP 4414 DI 10.1021/jm970549h PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YQ059 UT WOS:000071343300022 PM 9435910 ER PT J AU Aeschbach, D Matthews, JR Postolache, TT Jackson, MA Giesen, HA Wehr, TA AF Aeschbach, D Matthews, JR Postolache, TT Jackson, MA Giesen, HA Wehr, TA TI Dynamics of the human EEG during prolonged wakefulness: evidence for frequency-specific circadian and homeostatic influences SO NEUROSCIENCE LETTERS LA English DT Article DE electroencephalogram; spectral analysis; circadian rhythm; homeostatic process; constant routine protocol; evening wake-maintenance; sleepiness; body temperature ID WAKING EEG; SLEEP; PACEMAKER; TIME AB The electroencephalogram (EEG) of nine healthy individuals was recorded at half-hourly intervals during similar to 40 h of sustained wakefulness in a constant routine protocol. EEG power density in the 0.75-9.0 Hz range exhibited a global increasing trend, and a local trough in the evening, centered similar to 6 h prior to the temperature minimum. The former could be attributed to a wake-dependent influence, and the latter to a circadian influence. Power density in the 9.25-12.0 Hz band showed a circadian modulation, the trough coinciding with the minimum of the endogenous rhythm of body temperature, whereas a wake-dependent influence was not evident. Power density in the 12.25-25.0 Hz range exhibited a wake-dependent increase, whereas a circadian modulation was absent. It is concluded that the circadian pacemaker and the wake-dependent (i.e. homeostatic) process affect the waking EEG in a frequency-specific manner. (C) 1997 Elsevier Science Ireland Ltd. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RP Aeschbach, D (reprint author), NIMH, Clin Psychobiol Branch, Bldg 10,Rm 3s-231,10 Ctr Dr MSC 1390, Bethesda, MD 20892 USA. NR 20 TC 94 Z9 94 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 19 PY 1997 VL 239 IS 2-3 BP 121 EP 124 DI 10.1016/S0304-3940(97)00904-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA YT263 UT WOS:000071582200017 PM 9469671 ER PT J AU Abbracchio, MP Rainaldi, G Giammarioli, AM Ceruti, S Brambilla, R Cattabeni, F Barbieri, D Franceschi, C Jacobson, KA Malorni, W AF Abbracchio, MP Rainaldi, G Giammarioli, AM Ceruti, S Brambilla, R Cattabeni, F Barbieri, D Franceschi, C Jacobson, KA Malorni, W TI The A(3) adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bcl-x(L): Studies in human astroglioma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BCL-X; APOPTOSIS; EXPRESSION; N-6-BENZYLADENOSINE-5'-URONAMIDES; INDUCTION; AGONISTS; RAT; BAX AB The pathophysiological role of the adenosine As receptor in the central nervous system is largely unknown. We have investigated the effects of the selective A(3) receptor agonist 2-chloro-N-6-(3-iodobenzyl)-adenosine, Cl-IB-MECA, in cells of the astroglial lineage (human astrocytoma ADF cells). A marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions, was found following exposure of cells to low (nM) concentrations of Cl-IB-MECA. These "trophic" effects were accompanied by induction of the expression of Rho, a small GTP-binding protein, which was virtually absent in control cells, and by changes of the intracellular distribution of the antiapoptotic protein Bcl-x(L), that, in agonist-exposed cells, became specifically associated to cell protrusions. This is the first demonstration that the intracellular organization of Bcl-x(L) can be modulated by the activation of a G-protein coupled membrane receptor, such as the A(3) adenosine receptor. Moreover, modulation of the astrocytic cytoskeleton by adenosine may have intriguing implications in both nervous system development and in the response of the brain to trauma and ischemia. (C) 1997 Academic Press. C1 Univ Milan, Inst Pharmacol Sci, Milan, Italy. Ist Super Sanita, Dept Ultrastruct, I-00161 Rome, Italy. Dept Biomed Sci, Sect Gen Pathol, Modena, Italy. INRCA, Dept Gerontol, Ancona, Italy. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Abbracchio, MP (reprint author), Univ Milan, Inst Pharmacol Sci, Milan, Italy. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Malorni, Walter/G-5874-2016; Rainaldi, Gabriella/K-1315-2012 OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Rainaldi, Gabriella/0000-0001-7213-6853 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NIMH NIH HHS [1MH30003] NR 28 TC 72 Z9 72 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 18 PY 1997 VL 241 IS 2 BP 297 EP 304 DI 10.1006/bbrc.1997.7705 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ049 UT WOS:000071342300015 PM 9425266 ER PT J AU Owman, C Lolait, SJ Santen, S Olde, B AF Owman, C Lolait, SJ Santen, S Olde, B TI Molecular cloning and tissue distribution of cDNA encoding a novel chemoattractant-like receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXPRESSION; AIDS; HIV AB With the application of a homology screening strategy, including PCR amplification and southern blot hybridization, a novel cDNA was cloned from rat liver and anterior pituitary libraries. It was found to encode a 371-amino acid protein which has the characteristics of a heptahelix receptor and shows structural identity to members of the chemoattractant receptor family. A primary receptor message of 3.5 kb size was identified by northern blot hybridization. This RNA species showed high expression in heart and lung, while expression was lower in small intestines, colon, kidney, liver, uterus, and in brain. Another-larger RNA species of 6.3 kb appeared in heart and lung. In situ hybridization histochemistry performed on tissue from liver and kidney revealed a mainly vascular distribution of the receptor message. (C) 1997 Academic Press. C1 Univ Lund, Wallenberg Neurosci Ctr, Dept Physiol & Neurosci, Mol Neurobiol Sect, S-22362 Lund, Sweden. NIMH, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Owman, C (reprint author), Univ Lund, Wallenberg Neurosci Ctr, Dept Physiol & Neurosci, Mol Neurobiol Sect, S-22362 Lund, Sweden. NR 22 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 18 PY 1997 VL 241 IS 2 BP 390 EP 394 DI 10.1006/bbrc.1997.7822 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ049 UT WOS:000071342300030 PM 9425281 ER PT J AU Haynes, JI Gopal-Srivastava, R Piatigorsky, J AF Haynes, JI Gopal-Srivastava, R Piatigorsky, J TI alpha B-crystallin TATA sequence mutations: Lens-preference for the proximal TATA box and the distal TATA-like sequence in transgenic mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE crystallin; TATA box; promoter; heat shock; transgenic mouse; lens ID HEAT-SHOCK PROTEIN; RNA-POLYMERASE-II; A-CRYSTALLIN; GENE-EXPRESSION; MAMMALIAN-CELLS; PROMOTER; INITIATOR; TISSUES; TRANSCRIPTION; SPECIFICITY AB The mouse alpha B-crystallin promoter is active in lens (preferentially), heart and skeletal muscle, and contains a proximal (-28/-22) and distal (-76/-69) TATA sequence. The present investigation explores by site-specific mutagenesis of alpha B-crystallin promoter-chloramphenicol acetyltransferase (cat) reporter,bene constructs the function of these two potential TATA boxes in transfected lens cells and transgenic mice. Unexpectedly, mutagenesis of either or both TATA sequences had no effect on promoter activity in transfected lens cells. By contrast, in transgenic mice mutagenesis of the proximal, distal or both TATA sequences preferentially reduced promoter activity in the lens, with minimal effect in the heart or muscle. 5' RACE analysis of lens and muscle RNA of transgenic mice showed that elimination of the proximal TATA box led to transcription initiation at position -48. This upstream initiation site was apparently not due to the utilization of the distal TATA sequence, since the transgene carrying mutations in both TATA sequences also initiated at position -48. The preferential function of the distal TATA sequence in the lens is probably due to the binding of a transcription factor unrelated to transcription initiation, while the preferential lens function of the proximal TATA box appears to involve transcription initiation. (C) 1997 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP NEI, Mol & Dev Biol Lab, NIH, 6 Ctr Dr,MSC 2730,Bldg 6,Room 201, Bethesda, MD 20892 USA. NR 47 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 18 PY 1997 VL 241 IS 2 BP 407 EP 413 DI 10.1006/bbrc.1997.7833 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ049 UT WOS:000071342300033 PM 9425284 ER PT J AU Topol, IA Tawa, GJ Burt, SK Rashin, AA AF Topol, IA Tawa, GJ Burt, SK Rashin, AA TI Calculation of absolute and relative acidities of substituted imidazoles in aqueous solvent SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID DENSITY-FUNCTIONAL THEORY; BOUNDARY-ELEMENT METHOD; PROTON AFFINITIES; GAS-PHASE; SOLVATION ENERGIES; GAUSSIAN-2 THEORY; HYDRATION; WATER; MODEL; MOLECULES AB We calculate free energy changes of ionization reactions in aqueous solvent using a self-consistent reaction field method. In the calculations all species are treated as quantum mechanical solutes coupled to a solvent dielectric continuum. We show for a series of substituted imidazole compounds that both absolute and relative pK(a) values for the deprotonation of nitrogen on the imidazole ring can be obtained with an average absolute deviation of 0.8 units from experiment. This degree of accuracy is possible only if the solutes are treated at the correlated level using either G2 type or density functional theory. Inconsistencies in published experimental free energies of hydration that might undermine the reliability of the calculated absolute pK(a) values are discussed. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. BioChemComp Inc, Teaneck, NJ 07666 USA. RP Tawa, GJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick Biomed Supercomp Ctr, POB B, Frederick, MD 21702 USA. NR 67 TC 130 Z9 130 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD DEC 18 PY 1997 VL 101 IS 51 BP 10075 EP 10081 DI 10.1021/jp9723168 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA YP423 UT WOS:000071275300031 ER PT J AU Langer, RD Pierce, JJ OHanlan, KA Johnson, SR Espeland, MA Trabal, JF Barnabei, VM Merino, MJ Scully, RE AF Langer, RD Pierce, JJ OHanlan, KA Johnson, SR Espeland, MA Trabal, JF Barnabei, VM Merino, MJ Scully, RE TI Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ASYMPTOMATIC POSTMENOPAUSAL WOMEN; PREOPERATIVE ASSESSMENT; MYOMETRIAL INVASION; THICKNESS; SONOGRAPHY; CANCER; ADENOCARCINOMA; CARCINOMA AB Background Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial disease. However, its usefulness in screening for asymptomatic disease in postmenopausal women before or during treatment with estrogen or estrogen-progesterone replacement is not known. Methods We compared the sensitivity and specificity of transvaginal ultrasonography and endometrial biopsy for the detection of endometrial disease in 448 postmenopausal women who received estrogen alone, cyclic or continuous estrogen-progesterone, or placebo for three years. Results Concurrent ultrasonographic and biopsy results were available for 577 examinations in the 448 women, 99 percent of whom were undergoing routine annual follow-up. Endometrial thickness was less than 5 mm in 45 percent of the examinations, 5 to 10 mm in 41 percent, more than 10 mm in 12 percent, and not measured in 2 percent, and it was higher in the women receiving estrogen alone than in the other groups. Biopsy detected 11 cases of serious disease: 1 case of adenocarcinoma, 2 cases of atypical simple hyperplasia, and 8 cases of complex hyperplasia. Biopsy also detected simple hyperplasia in 20 cases. At a threshold value of 5 mm for endometrial thickness. transvaginal ultrasonography had a positive predictive value of 9 percent for detecting any abnormality, with 90 percent sensitivity, 48 percent specificity, and a negative predictive value of 99 percent. With this threshold, a biopsy would be indicated in more than half the women, only 4 percent of whom had serious disease. Conclusions Transvaginal ultrasonography has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease in asymptomatic postmenopausal women. (C) 1997, Massachusetts Medical Society. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. STANFORD UNIV,DEPT OBSTET & GYNECOL,PALO ALTO,CA 94304. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. UNIV TEXAS,HLTH SCI CTR,DEPT OBSTET & GYNECOL,SAN ANTONIO,TX 78284. GEORGE WASHINGTON UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20037. NATL CANC INST,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Langer, RD (reprint author), UNIV CALIF SAN DIEGO,DEPT FAMILY & PREVENT MED,9500 GILMAN DR,MC 0978,LA JOLLA,CA 92093, USA. OI Barnabei, Vanessa/0000-0002-9650-0143; O'Hanlan, Katherine/0000-0002-7577-4188 FU NHLBI NIH HHS [U01-HL40185, U01-HL40154, U01-HL40195] NR 25 TC 135 Z9 140 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 DEC 18 PY 1997 VL 337 IS 25 BP 1792 EP 1798 DI 10.1056/NEJM199712183372502 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YL855 UT WOS:A1997YL85500002 PM 9400035 ER PT J AU Patterson, BH KrebsSmith, SM Subar, AF AF Patterson, BH KrebsSmith, SM Subar, AF TI Correction and revision of conclusions - Dietary trends in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Patterson, BH (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 5 Z9 5 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 1997 VL 337 IS 25 BP 1846 EP 1846 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YL855 UT WOS:A1997YL85500013 PM 9411260 ER PT J AU Ferguson, JH Hall, WH AF Ferguson, JH Hall, WH TI Prepublication of NIH Consensus Conferences on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Ferguson, JH (reprint author), NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 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 DEC 17 PY 1997 VL 278 IS 23 BP 2063 EP 2064 DI 10.1001/jama.278.23.2063 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YK987 UT WOS:A1997YK98700024 PM 9403414 ER PT J AU Harlan, WL AF Harlan, WL TI Clinical trial investigators talk about getting the data. (vol 277, pg 1833, 1997) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Correction, Addition RP Harlan, WL (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 17 PY 1997 VL 278 IS 23 BP 2064 EP 2064 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YK987 UT WOS:A1997YK98700026 ER PT J AU Bollinger, RC Brookmeyer, RS Mehendale, SM Paranjape, RS Shepherd, ME Gadkari, DA Quinn, TC AF Bollinger, RC Brookmeyer, RS Mehendale, SM Paranjape, RS Shepherd, ME Gadkari, DA Quinn, TC TI Risk factors and clinical preservation of acute primary HIV infection in India SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDEMIC; VIREMIA AB Context.-Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias. Objectives.-To apply a method based on measurement of prevalent HIV-1 p24 antigenemia for identification of risk factors for newly acquired HIV infection and to describe the signs and symptoms of acute HIV infection. Design and Setting.-Nested case-control study in Pune, India. Participants.-HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996. Outcome Measures.-Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection. Results.-Of 3874 HIV antibody-negative persons tested, 58 (1.5%) were p24 antigen positive at initial presentation to the clinics. Unprotected sexual contact with a commercial sex worker (CSW) was reported by 39 (77%) of the 51 p24 antigenemic men, compared with 131 (51%) of 255 control men (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.2-9.6; P=.02). The presence of an active genital ulcer at the time of screening was found in 46 (79%) of the 58 p24 antigenemic men and women, compared with 137 (47%) of the 290 control subjects (AOR, 4.2; 95% CI, 2.0-9.0; P<.001). Signs and symptoms independently associated with p24 antigenemia in HIV antibody-seronegative persons included fever, which was reported by 28 (48%) of the 58 p24 antigenemic subjects, but only 52 (18%) of the 290 control subjects (AOR, 4.7; 95% CI, 2.4-9.0; P<.001). Joint pain was reported by 10% of subjects recently HIV infected, compared with 2% of the control subjects (AOR, 6.5; 95% CI, 1.7-24.8; P=.006), Night sweats were reported by 9% of the p24 antigenemic, but only 1% of the control subjects (AOR, 9.1; 95% CI, 1.7-47.6; P=.009), Overall, fever, joint pain, and/or night sweats were reported in 27 (47%) of the 58 subjects with recent HIV infection. Conclusions.-This systematic case-control study of p24 antigen screening in HIV-seronegative patients attending STD clinics in India identified unprotected sex with a CSW and a genital ulcer as independent risk factors associated with newly acquired HIV infection. In addition, p24 antigen positivity identified recent fever, night sweats, and arthralgias as symptoms that may be predictive of recent HIV infection, In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV INFECT DIS,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. NATL AIDS RES INST,PUNE,MAHARASHTRA,INDIA. NIAID,NIH,BETHESDA,MD 20892. FU FIC NIH HHS [D43TW0000]; NIAID NIH HHS [AI 33879-02] NR 15 TC 84 Z9 85 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 DEC 17 PY 1997 VL 278 IS 23 BP 2085 EP 2089 DI 10.1001/jama.278.23.2085 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YK987 UT WOS:A1997YK98700038 PM 9403423 ER PT J AU Gangakhedkar, RR Bentley, ME Divekar, AD Gadkari, D Mehendale, SM Shepherd, ME Bollinger, RC Quinn, TC AF Gangakhedkar, RR Bentley, ME Divekar, AD Gadkari, D Mehendale, SM Shepherd, ME Bollinger, RC Quinn, TC TI Spread of HIV infection in married monogamous women in India SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; IMMUNODEFICIENCY-VIRUS TYPE-1; EPIDEMIC; CLINICS AB Context.-A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses al risk for spread of infection to other populations. Objective.-To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs. Methods.-Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed. Main Outcome Measure.-Prevalence and risk determinants of HIV infection. Results.-Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (P<.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs. Conclusions.-Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NATL AIDS RES INST,PUNE,MAHARASHTRA,INDIA. NIAID,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RI Quinn, Thomas/A-2494-2010 FU FIC NIH HHS [D43-TW0000]; NCRR NIH HHS [RR-00722]; NIAID NIH HHS [AI-33879] NR 15 TC 191 Z9 193 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 DEC 17 PY 1997 VL 278 IS 23 BP 2090 EP 2092 DI 10.1001/jama.278.23.2090 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YK987 UT WOS:A1997YK98700039 PM 9403424 ER PT J AU Cinciripini, PM Hecht, SS Henningfield, JE Manley, MW Kramer, BS AF Cinciripini, PM Hecht, SS Henningfield, JE Manley, MW Kramer, BS TI Tobacco addiction: Implications for treatment and cancer prevention SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID SMOKING CESSATION; CIGARETTE-SMOKING; MAJOR DEPRESSION; NICOTINE PATCH; UNITED-STATES; MUTAGEN SENSITIVITY; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK; PHENETHYL ISOTHIOCYANATE; WITHDRAWAL SYMPTOMS; AFRICAN-AMERICANS AB The American Society of Clinical Oncology and the National Cancer Institute convened a symposium in June 1996 on tobacco addiction, Additional support for the symposium was provided by the American Medical Women's Association and the American Society of Preventive Oncology, The goals of this conference were to describe the burden and public health consequences of tobacco addiction, to describe the state of science for the treatment of nicotine dependence, and to explore new strategies to increase quit rates and to prevent the uptake of tobacco use, This article summarizes and integrates the meeting presentations on tobacco addiction and includes the topics of smoking prevalence; psychobiologic aspects of nicotine dependence; and implications for disease, treatment, and prevention, Comments on regulatory approaches and national strategies for reducing dependence are also summarized in presentations by Dr, David Kessler, former Food and Drug Administration Commissioner, and Dr. C. Everett Koop, former U.S. Surgeon General. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Behav Sci, Houston, TX 77302 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Pinney Associates, Baltimore, MD USA. NCI, Canc Control Res Program, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Cinciripini, PM (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Behav Sci, Box 243,1515 Holcombe Blvd, Houston, TX 77302 USA. RI Cinciripini, Paul/I-5773-2012; OI Cinciripini, Paul/0000-0003-2877-9928; Hecht, Stephen/0000-0001-7228-1356 NR 162 TC 44 Z9 52 U1 5 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 17 PY 1997 VL 89 IS 24 BP 1852 EP 1867 DI 10.1093/jnci/89.24.1852 PG 16 WC Oncology SC Oncology GA YM070 UT WOS:000071024900010 PM 9414173 ER PT J AU Perlman, JH Colson, AO Jain, R Czyzewski, B Cohen, LA Osman, R Gershengorn, MC AF Perlman, JH Colson, AO Jain, R Czyzewski, B Cohen, LA Osman, R Gershengorn, MC TI Role of the extracellular loops of the thyrotropin-releasing hormone receptor: Evidence for an initial interaction with thyrotropin-releasing hormone SO BIOCHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; TRH RECEPTOR; BINDING POCKET; LIGAND-BINDING; REFINED MODEL; CHORIOGONADOTROPIN; MINIMIZATION; SELECTIVITY; COMPLEX; ENERGY AB Thyrotropin-releasing hormone (TRH), like most small ligands, appears to bind within the seven transmembrane-spanning helices (TMs) of its G protein-coupled receptor (TRH-R), A role for the extracellular loops (ECLs) of TRH-R has not been established, We substituted residues in the ECLs of TRH-R and show that Tyr-181 is important for high-affinity binding because its substitution leads to a 3700-fold lowering of the estimated affinity compared to wild-type TRH-R. Using TRH analogues, we provide evidence that there is a specific interaction between Tyr-181 in ECL-2 and the pyroGlu moiety of TRH, It was previously suggested that the pyroGlu of TRH may interact with Asn-110 in TM-3 and with Asn-289 in ECL-3; N110A and N289A TRH-Rs exhibit similar apparent affinities that are only 20-30-fold lower than wild-type TRH-R, To better understand these findings, we analyzed a computer-generated model which predicts that the ECLs form an entry channel into the TRH-R TM bundle, that Tyr-181 projects into this channel and that the pyroGlu of TRH cannot simultaneously interact with residues in the TMs and ECLs. Kinetic analysis showed that the association rate of [N-tau-methyl-His]TRH with N289A TRH-R is slower than with wild-type TRH-R and largely accounts for the lower apparent affinity; the association rate with N110A TRH-R is similar to that of wild-type TRH-R. These data are consistent with the idea that there are initial interactions between TRH and the residues of a putative entry channel of TRH-R. We suggest that a role of the EC Ls in all G protein-coupled receptors for small ligands maybe to initially contact the ligand and allow entry into a TM binding pocket. C1 Cornell Univ, Coll Med, Dept Med, Div Mol Med, New York, NY 10021 USA. CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Perlman, JH (reprint author), Cornell Univ, Coll Med, Dept Med, Div Mol Med, 1300 York Ave,Room A328, New York, NY 10021 USA. FU NIDDK NIH HHS [DK 02101, DK 09647, DK 43036] NR 32 TC 43 Z9 44 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 16 PY 1997 VL 36 IS 50 BP 15670 EP 15676 DI 10.1021/bi9713310 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN267 UT WOS:000071149800013 PM 9398295 ER PT J AU Rigby, AC Baleja, JD Li, LP Pedersen, LG Furie, BC Furie, B AF Rigby, AC Baleja, JD Li, LP Pedersen, LG Furie, BC Furie, B TI Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus SO BIOCHEMISTRY LA English DT Article ID 2-DIMENSIONAL NMR-SPECTROSCOPY; PHOSPHOLIPID-BINDING SITE; BLOOD-COAGULATION; MEMBRANE-BINDING; FACTOR-IX; CONFORMATIONAL TRANSITIONS; PROTHROMBIN FRAGMENT-1; GLA DOMAIN; ION; RESIDUES AB Conantokin G is a gamma-carboxyglutamic acid- (Gla-) containing conotoxin isolated from the venom of the marine cone snail Conus geographus. This 17-residue polypeptide, which contains five gamma-carboxyglutamic acid residues, is a N-methyl-D-aspartate- (NMDA-) type glutamate receptor antagonist. To investigate the role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, we determined the three-dimensional structure of the conantokin G/Ca2+ complex by two-dimensional H-1 NMR spectroscopy and compared it to the high-resolution structure of conantokin G in the absence of metal ions [Rigby et al. (1997) Biochemistry 36, 6906]. Complete resonance assignments were made by two dimensional 1H NMR spectroscopy at pH 5.6 in the presence of saturating amounts of Ca2+. Distance geometry and simulated annealing methods were used to derive 23 convergent structures from a set of 302 interproton distance restraints and two torsion angle measurements. A high-resolution structure, with the backbone root mean square deviation to the geometric average of the 23 structures of 0.6 +/- 0.1 Angstrom, contains a linear alpha-helix from Gla 3 to Lys 15. Gla residues 3, 7, 10, and 14 are aligned in a linear array on one face of the helix. A genetic algorithm was applied to determine the calcium positions in conantokin G, and the conantokin G/Ca2+ complex refined by molecular simulation. Upon binding of Ca2+ to gamma-carboxyglutamic acid, conantokin G undergoes a conformational transition from a distorted curvilinear 3(10) helix to a linear alpha-helix. Occupancy of the metal binding sites, defined by gamma-carboxyglutamic acids, results in formation of a calcium-carboxylate network that linearizes the helix and exposes the hydrophobic amino acids on the opposite face of the helix. C1 Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Tufts Univ, Sch Med, New England Med Ctr, Div Hematol Oncol,Ctr Hemostasis & Thrombosis Res, Boston, MA 02111 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL18834, HL38216, HL42443] NR 37 TC 47 Z9 49 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 16 PY 1997 VL 36 IS 50 BP 15677 EP 15684 DI 10.1021/bi9718550 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN267 UT WOS:000071149800014 PM 9398296 ER PT J AU Forsberg, EC Lam, LT Yang, XJ Nakatani, Y Bresnick, EH AF Forsberg, EC Lam, LT Yang, XJ Nakatani, Y Bresnick, EH TI Human histone acetyltransferase GCN5 exists in a stable macromolecular complex lacking the adapter ADA2 SO BIOCHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR NF-E2; YEAST PUTATIVE ADAPTERS; CHROMATIN STRUCTURE; MULTISUBUNIT COMPLEX; PROMOTER ACTIVATION; NUCLEOSOMAL DNA; TRANSGENIC MICE; GENE-PRODUCTS AB Acetylation of core histones is an important regulatory step in transcriptional activation from chromatin templates. The yeast transcriptional coactivator protein GCN5 was recently shown to be a nuclear histone acetyltransferase (HAT). Genetic and biochemical studies in yeast suggest that GCN5 functions with the adapter proteins ADA1, ADA2, ADA3, and ADAS in a heteromeric complex. We have established conditions for chromatographic fractionation of HATs and ADA2 from human K562 erythroleukemia cells. Gel-filtration chromatography revealed two populations of GCN5 with Stokes' radii of 67 and 33 Angstrom, consistent with a large macromolecular complex and a monomer. respectively. The GCN5-related HAT, PCAF, was resolved as a stable complex with a Stokes' radius of 74 Angstrom. The HAT complexes were resistant to 0.3 M NaCl and DNase I. ADA2 was characterized by a Stokes' radius of 35 Angstrom, consistent with a monomer. Thus, in contrast to the stable GCN5-adapter complex in yeast, human GCN5 and ADA2 are not stably associated with each other. The implications of this result are discussed vis-a-vis the mechanism of recruitment of GCN5 to regulatory regions of genes. C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Bresnick, EH (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, 387 Med Sci Bldg,1300 Univ Ave, Madison, WI 53706 USA. FU NIDDK NIH HHS [DK50107] NR 49 TC 16 Z9 17 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 DEC 16 PY 1997 VL 36 IS 50 BP 15918 EP 15924 DI 10.1021/bi971664x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN267 UT WOS:000071149800043 PM 9398325 ER PT J AU Nebigil, CG AF Nebigil, CG TI Suppression of phospholipase C beta, gamma, and delta families alters cell growth and phosphatidylinositol 4,5-bisphosphate levels SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ALPHA-SUBUNITS; DNA-SYNTHESIS; RECEPTOR; ACTIVATION; MITOGENESIS; HYDROLYSIS; ISOZYMES; SIGNAL; GQ AB Phosphatidylinositol-specific phospholipase C (PLC) activity reflects a summation of the activities of three families, beta, gamma, and delta, each of which is regulated differently. In order to understand the contribution of each family to cell proliferation signaling, expression of each family was suppressed by use of an inducible expression vector for antisense PLC sequences in a single cell line, FTO-2B rat hepatocytes. Activation of second messengers of PLC [diacylglycerol (DAG) and inositol 1,4,5-tris-(phosphate) (IP3)] was dramatically reduced, providing a strategy for probing the consequences of PLC deficiency on cell function. Importantly, while one PLC family was suppressed, the other PLCs actively responded to specific stimuli, suggesting parallel and independent signaling pathways for each PLC family in FTO-2B cells. Selective suppression of each PLC family altered cell growth markedly and differentially. The rank order for suppression of cell growth by loss of a PLC family was gamma > delta > beta. Exploration of down-stream growth regulators revealed that loss of beta and gamma, but not delta, families was associated with markedly reduced basal ms and protein kinase C activity. Moreover, suppression of each of the three PLC families caused remarkably reduced basal and stimulated MAP kinase activities. Interestingly, cellular levels of PIP2 were increased and dramatically correlated with growth inhibition rate in the clones with suppressed PLC activity, suggesting that PIP2 itself can serve as a second messenger of cell growth regulation. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Nebigil, CG (reprint author), Inst Genet & Biol Mol & Cellulaire, 1 Laurent Fries,BP 163, F-67404 Illkirch Graffenstaden, France. NR 51 TC 27 Z9 28 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 DEC 16 PY 1997 VL 36 IS 50 BP 15949 EP 15958 DI 10.1021/bi971721m PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN267 UT WOS:000071149800047 PM 9398329 ER PT J AU Ha, SB Melman, N Jacobson, KA Nair, V AF Ha, SB Melman, N Jacobson, KA Nair, V TI New base-altered adenosine analogues: Synthesis and affinity at adenosine A(1) and A(2A) receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PURINE NUCLEOSIDES; BRAIN; ADENOSINE-A1-RECEPTOR; AGONISTS AB N-6-Substituted adenosine analogues containing cyclic hydrazines or chiral hydroxy (ar)alkyl groups, designed to interact with the S2 and S3 receptor subregions, have been synthesized and their binding to the adenosine A(1) and A(2A) receptors have been investigated. Examples of both types of compounds were found to exhibit highly selective binding (K-i in low nM range) to the rat A(1) receptor. (C) 1997 Elsevier Science Ltd. C1 Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Nair, V (reprint author), Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 22 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 16 PY 1997 VL 7 IS 24 BP 3085 EP 3090 DI 10.1016/S0960-894X(97)10177-9 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA YN348 UT WOS:000071158900003 PM 25147430 ER PT J AU Hwang, DM Dempsey, AA Wang, RX Rezvani, M Barrans, JD Dai, KS Wang, HY Ma, H Cukerman, E Liu, YQ Gu, JR Zhang, JH Tsui, SKW Waye, MMY Fung, KP Lee, CY Liew, CC AF Hwang, DM Dempsey, AA Wang, RX Rezvani, M Barrans, JD Dai, KS Wang, HY Ma, H Cukerman, E Liu, YQ Gu, JR Zhang, JH Tsui, SKW Waye, MMY Fung, KP Lee, CY Liew, CC TI A genome-based resource for molecular cardiovascular medicine - Toward a compendium of cardiovascular genes SO CIRCULATION LA English DT Article DE cardiomyopathy; cardiovascular diseases; cDNA library; expressed sequence tags; heart failure; human genome project; hypertrophy ID EXPRESSED SEQUENCE TAGS; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; HEART CDNA LIBRARY; CARDIAC TROPONIN-T; PRESSURE-OVERLOAD; CHROMOSOMAL LOCALIZATION; NATRIURETIC-PEPTIDE; POSITIONAL CLONING; ALPHA-TROPOMYOSIN; HUMAN BRAIN AB Background Large-scale partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of discovering novel genes and characterizing transcription patterns in different tissues. To catalogue the identities and expression levels of genes in the cardiovascular system, we initialed large-scale sequencing and analysis of human cardiac cDNA libraries. Methods and Results Using automated DNA sequencing, we generated 43 285 ESTs from human heart cDNA libraries. An additional 41 619 ESTs were retrieved from public databases, for a total of 84 904 ESTs representing more than 26 million nucleotides of raw cDNA sequence data from 13 independent cardiovascular system-based cDNA libraries. Of these, 55% marched to known genes in the Genbank/EMBL/DDBJ databases, 33% matched only to other ESTs, and 12% did not match to any known sequences (designated cardiovascular system-based ESTs, or CVbESTs). ESTs that matched to known genes were classified according to function, allowing for detection of differences in general transcription patterns between various tissues and developmental stages of the cardiovascular system. In silico Northern analysis of known gene matches identified widely expressed cardiovascular genes as well as genes putatively exhibiting greater tissue specificity or developmental stage specificity. More detailed analysis identified 48 genes potentially overexpressed in cardiac hypertrophy, at least 10 of which were previously documented as differentially expressed. Computer-based chromosomal localizations of 1048 cardiac ESTs ware performed to further assist in the search for disease-related genes. Conclusions These data represent the most extensive compilation of cardiovascular gene expression information to date. They further demonstrate the untapped potential of genome research for investigating questions related to cardiovascular biology and represent a first-generation genome-based resource for molecular cardiovascular medicine. C1 UNIV TORONTO,TORONTO HOSP,CARDIOVASC RES CTR,CARDIAC GENE UNIT,DEPT LAB MED,TORONTO,ON,CANADA. UNIV TORONTO,TORONTO HOSP,CARDIOVASC RES CTR,CARDIAC GENE UNIT,DEPT PATHOBIOL,TORONTO,ON,CANADA. UNIV TORONTO,TORONTO HOSP,CARDIOVASC RES CTR,CARDIAC GENE UNIT,DEPT MED,TORONTO,ON,CANADA. CHINA NATL CTR BIOTECHNOL DEV,STC,BEIJING,PEOPLES R CHINA. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. CHINESE UNIV HONG KONG,DEPT BIOCHEM,SHATIN,HONG KONG. RI Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tsui, Stephen Kwok-Wing/E-4385-2015 OI Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tsui, Stephen Kwok-Wing/0000-0003-0686-4259 NR 68 TC 152 Z9 165 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 16 PY 1997 VL 96 IS 12 BP 4146 EP 4203 PG 58 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YL375 UT WOS:A1997YL37500010 PM 9416882 ER PT J AU Hwang, SJ Ballantyne, CM Sharrett, AR Smith, LC Davis, CE Gotto, AM Boerwinkle, E AF Hwang, SJ Ballantyne, CM Sharrett, AR Smith, LC Davis, CE Gotto, AM Boerwinkle, E TI Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases - The atherosclerosis risk in communities (ARIC) study SO CIRCULATION LA English DT Article DE atherosclerosis; coronary heart disease; adhesion molecules ID ACUTE MYOCARDIAL-INFARCTION; CULTURED ENDOTHELIAL-CELLS; ARTERY DISEASE; COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS; MONONUCLEAR-CELLS; SOLUBLE FORMS; KAPPA-B; EXPRESSION; PATHOGENESIS AB Background Recruitment of circulating leukocytes at sites of atherosclerosis is mediated through a family of adhesion molecules. The function of circulating forms of these adhesion molecules remains unknown, but their levels may serve as molecular markers of subclinical coronary heart disease (CHD). Methods and Results To determine the ability of circulating vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intercellular adhesion molecule-1 (ICAM-1) to serve as molecular markers of atherosclerosis and predictors of incident CHD, we studied 204 patients with incident CHD, 272 patients with carotid artery atherosclerosis (CAA), and 316 control subjects from the large, biracial Atherosclerosis Risk In Communities (ARIC) study. Levels of VCAM-1 were not significantly different among the patients with incident CHD, those with CAA, and control subjects. Higher levels of E-selectin and ICAM-1 were observed for the patients with CHD (means [ng/mL]: E-selectin, 38.4; ICAM-1, 288.7) and those with CAA (E-selectin, 41.5; ICAM-1, 283.6) compared with the control subjects (E-selectin, 32.8; ICAM-1, 244.2), but the distributions were not notably different between the patients with CHD and CAA. Results of logistic regression analyses indicated that the relationship of ICAM-1 and E-selectin with CHD and CAA was independent of other known CHD risk factors and was most pronounced in the highest quartile. The odds of CHD and CAA were 5.53 (95% CI, 2.51-12.21) and 2.64 (95% CI, 1.40-5.01), respectively, for those with levels of ICAM-1 in the highest quartile compared with those in the lowest quartile. Odds of CAA were 2.03 (95% CI, 1.14-3.62) for those with levels of E-selectin in the highest quartile compared with those in the lowest quartile. Conclusions These data indicate that plasma levels of ICAM-1 and E-selectin may serve as molecular markers for atherosclerosis and the development of CHD. C1 UNIV TEXAS,HLTH SCI CTR,CTR HUMAN GENET,HOUSTON,TX 77225. UNIV TEXAS,HLTH SCI CTR,INST MOL MED,HOUSTON,TX 77225. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. RI Ballantyne, Christie/A-6599-2008 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 61 TC 907 Z9 965 U1 5 U2 24 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 16 PY 1997 VL 96 IS 12 BP 4219 EP 4225 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YL375 UT WOS:A1997YL37500013 PM 9416885 ER PT J AU Dalakas, MC AF Dalakas, MC TI Meningitis and skin reaction after intravenous immune globulin therapy - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID IMMUNOGLOBULIN C1 NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NIH, Bethesda, MD 20892 USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1997 VL 127 IS 12 BP 1130 EP 1130 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YL262 UT WOS:000070936600019 ER PT J AU Mori, T Itoh, S Ohgiya, S Ishizaki, K Kamataki, T AF Mori, T Itoh, S Ohgiya, S Ishizaki, K Kamataki, T TI Regulation of CYP1A and CYP3A mRNAs by ascorbic acid in guinea pigs SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; CYP3A; CYP1A; ascorbic acid; guinea pig ID LIVER MICROSOMAL CYTOCHROME-P-450; HUMAN-FETAL LIVERS; METABOLIC-ACTIVATION; DRUG-METABOLISM; RAT-LIVER; MOLECULAR-CLONING; DEFICIENCY; SEQUENCES; FORMS; PURIFICATION AB In previous studies, we found that the ascorbic acid (AsA) deficiency caused changes in the amounts of the various forms of cytochrome P450 (P450) in liver microsomes from guinea pigs in a form-specific manner, Thus, the aim of this study was to clarify whether the changes seen in the protein contents of the various forms of P450 were associated with the levels of the expression of their mRNAs, Prior to determining the mRNA level, we isolated four cDNA clones, encoding CYP1A2, CYP3A14, CYP3A15,and CYP3A17, from guinea pig liver cDNA libraries to use them as probes in further experiments. The amino acid sequence of the guinea pig CYP1A2 showed identity ranging from 73 to 77% with those of other mammalian P450s. The amino acid sequences among guinea pig CYP3As had about 94% identities with each other. The AsA deficiency apparently decreased the expression of mRNA for CYP1A1 and CYP1A2. These results were in agreement with the decrease in the content of CYP1A1 and CYP1A2 proteins, The amount of P450 protein(s) immunochemically cross-reactive with antibodies to human CYP3A4 was likely unaffected while that of human CYP3A7 tended to be decreased by the AsA deficiency. If suggested that the expression of each CYP3A isozyme was regulated differently by Ask In fact, the level of mRNA for CYP3A14 was unaffected by the AsA deficiency, while those for CYP3A15 and CYP3A17 were significantly decreased by the AsA deficiency, clearly indicating that the expression of each isozyme within the CYP3A subfamily is differently regulated by AsA, These results support the idea that the transcription of P450 is regulated by AsA in guinea pigs. (C) 1997 Academic Press. C1 Hokkaido Univ, Fac Pharmaceut Sci, Div Drug Metab, Sapporo, Hokkaido 060, Japan. Hokkaido Natl Ind Res Inst, Biosci Chem Div, Sapporo, Hokkaido 062, Japan. RP Mori, T (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment,Dev Therapeut Program, Diagnosis & Ctr,Lab Drug Res & Dev, Bldg 1052,room 105, Frederick, MD 21702 USA. NR 54 TC 17 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 15 PY 1997 VL 348 IS 2 BP 268 EP 277 DI 10.1006/abbi.1997.0409 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YP215 UT WOS:000071254100006 PM 9434738 ER PT J AU Jonsson, EG Mirsky, AF Johannesson, T Wahlstrom, J Bieliauskas, LA van Kammen, DP Sedvall, GC AF Jonsson, EG Mirsky, AF Johannesson, T Wahlstrom, J Bieliauskas, LA van Kammen, DP Sedvall, GC TI No cytogenetical abnormalities in a set of schizophrenic quadruplets SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID GENAIN QUADRUPLETS; TRIPLETS; FAMILY C1 Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, SE-17176 Stockholm, Sweden. NIMH, Sect Clin & Expt Neuropsychol, Bethesda, MD 20892 USA. East Hosp, Dept Clin Genet, Gothenburg, Sweden. VA Med Ctr, Psychol Serv, Ann Arbor, MI USA. Univ Michigan, Hosp Med, Dept Psychiat, Neuropsychol Program, Ann Arbor, MI 48109 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Jonsson, EG (reprint author), Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, SE-17176 Stockholm, Sweden. NR 16 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1997 VL 42 IS 12 BP 1186 EP 1187 DI 10.1016/S0006-3223(97)00393-4 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YM224 UT WOS:000071042200016 PM 9426891 ER PT J AU Sato, T Selleri, C Young, NS Maciejewski, JP AF Sato, T Selleri, C Young, NS Maciejewski, JP TI Inhibition of interferon regulatory factor-1 expression results in predominance of cell growth stimulatory effects of interferon-gamma due to phosphorylation of Stat1 and Stat3 SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW; GENE-EXPRESSION; FACTOR-ALPHA; FACTOR-I; TRANSCRIPTIONAL INDUCTION; APLASTIC-ANEMIA; T-LYMPHOCYTES; IFN-GAMMA AB Interferon-gamma (IFN-gamma) is a potent inhibitor of hematopoiesis in vitro and has been implicated in the pathophysiology of human bone marrow failure syndromes. IFN-gamma both inhibits cell cycling and induces expression of the Fas-receptor, resulting in subsequent apoptosis of hematopoietic progenitor cells. IFN regulatory factor-1 (IRF-1) mediates some of these suppressive effects by activation of downstream inducible genes, such as double-stranded RNA-activatable protein kinase and inducible nitric oxide synthase. However, under certain experimental conditions, IFN-gamma appears to stimulate proliferation of hematopoietic cells. Based on the hypothesis that IFN-gamma-receptor triggering may activate diverse signaling cascades, we designed experiments to determine which intracellular mechanisms (in addition to the IRF-1 transduction pathway) influence the biologic effects of IFN-gamma. Using antisense technique, we inhibited the IRF-1-mediated pathway in KG1a cells stimulated with IFN-gamma. In contrast to the suppressive effects of IFN-gamma observed in control cells, untreated and IFN-gamma-treated KG1a cells that were transduced with retroviral vectors expressing IRF-1 antisense mRNA showed enhanced proliferation. The increased growth rate was associated with decreased levels of IRF-1 mRNA and protein but unchanged levels of IRF-2. We inferred that IFN-gamma could also activate a stimulatory transduction pathway that, under specific conditions, may control the cellular response to this cytokine. The family of Stat proteins is involved in signal transduction of hematopoietic growth factors. We showed that, in KG-la cells, IFN-gamma also induced phosphorylation of Stat1 and Stat3, whereas p42 MAP kinase was phosphorylated regardless of the presence of IFN-gamma. Using electrophoresis mobility shift assays, IFN-gamma enhanced Stat1-Stat1 homodimer and Stat1-Stat3 heterodimer formation, suggesting that, in addition to inhibitory signals mediated by IRF-1, IFN-gamma may activate proliferative signals by phosphorylation of Stat1 and Stat3 proteins. The observations made in experiments with KG-la cells were confirmed in primary hematopoietic cells. After inhibition of the IRF-1 pathway by transduction of an antisense IRF-1 retrovirus into human CD34(+) cells, IFN-gamma produced an aberrant stimulatory effect on hematopoietic colony formation. Conversely, in control vector-transduced CD34(+) cells, the typical inhibitory response to IFN-gamma was seen. Our results indicate that inhibitory cytokines such as IFN-gamma may exhibit diverse biologic effects depending on the intracellular balance of transcriptional regulators, in turn influenced by the activation and differentiation status of the target cells. (C) 1997 by The American Society of Hematology. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 53 TC 54 Z9 56 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1997 VL 90 IS 12 BP 4749 EP 4758 PG 10 WC Hematology SC Hematology GA YJ908 UT WOS:A1997YJ90800011 PM 9389691 ER PT J AU Yen, T Harrison, CA Devery, JM Leong, S Iismaa, SE Yoshimura, T Geczy, CL AF Yen, T Harrison, CA Devery, JM Leong, S Iismaa, SE Yoshimura, T Geczy, CL TI Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; MONOCYTIC DIFFERENTIATION; FACTOR EXPRESSION; GENE-EXPRESSION; MESSENGER-RNA; IN-VITRO; BINDING; ACTIVATION; MRP14 AB Microvascular endothelial cells (EC) have multiple functions in inflammatory responses, including the production of chemoattractants that enhance leukocyte transmigration into tissues. Chemotactic protein, 10 kD (CP-10), is an S100 protein with potent chemotactic activity for myeloid cells in vitro and in vivo and is expressed in neutrophils and lipopolysaccharide (LPS)-activated macrophages. We show here that CP-10 is induced in murine endothelioma cell lines (bEnd-3. sEnd-1. and tEnd-1) after activation with LPS and interteukin-1 (IL-1) but not tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma). Induction was not mediated by endogenous release of IL-1 or TNF alpha and was not directly upregulated by phorbol myristate acetate, calcium ionophore, or vitamin D3. EC were exquisitely sensitive to IL-1 activation (3.4 U/mL) and CP-10 mRNA induction with IL-1 occurred earlier (8 hours) than with LPS (12 hours). Furthermore, some microvessels and capillaries in delayed-type hypersensitivity lesions expressed cytoplasmic CP-10. Responses to LPS and not II-1 in vitro were regulated by the degree of cell confluence and by TNF alpha costimulation. The related MRP14 mRNA had a different induction pattern. Monomeric and homodimeric CP-10 upregulated by activation was predominantly cell-associated. EC-derived CP-10 may contribute to amplification of inflammatory processes by enhancing leukocyte shape changes and transmigration in the microcirculation. (C) 1997 by The American Society of Hematology. C1 ST VINCENTS HOSP,VICTOR CHANG CARDIAC RES INST,SYDNEY,NSW 2010,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. RP Yen, T (reprint author), UNIV NEW S WALES,SCH PATHOL,FAC MED,KENSINGTON,NSW 2052,AUSTRALIA. RI Iismaa, Siiri/A-9924-2008; Iismaa, Siiri/C-9300-2013 OI Iismaa, Siiri/0000-0003-2409-7356 NR 46 TC 69 Z9 73 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1997 VL 90 IS 12 BP 4812 EP 4821 PG 10 WC Hematology SC Hematology GA YJ908 UT WOS:A1997YJ90800018 PM 9389698 ER PT J AU Mori, N Kashanchi, F Prager, D AF Mori, N Kashanchi, F Prager, D TI Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53 SO BLOOD LA English DT Article ID TUMOR-SUPPRESSOR GENE; HTLV-I; FREQUENT MUTATIONS; TRANSFORMED-CELLS; PROVIRUS GENOME; INFECTED-CELLS; TAX PROTEINS; EXPRESSION; ACTIVATION; ANTIGEN AB Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-l-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-l-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1 alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax. a T-cell line stably expressing Tax, and MT-2, a HTLVI-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL. (C) 1997 by The American Society of Hematology. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90024. NCI,MOL VIROL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [R01-DK46484] NR 58 TC 16 Z9 16 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 DEC 15 PY 1997 VL 90 IS 12 BP 4924 EP 4932 PG 9 WC Hematology SC Hematology GA YJ908 UT WOS:A1997YJ90800030 PM 9389710 ER PT J AU Sabatino, DE Do, BKQ Pyle, LC Seidel, NE Girard, LJ Spratt, SK Orlic, D Bodine, DM AF Sabatino, DE Do, BKQ Pyle, LC Seidel, NE Girard, LJ Spratt, SK Orlic, D Bodine, DM TI Amphotropic or Gibbon ape leukemia virus (GaLV) retrovirus binding and transduction correlates with the level of receptor mRNA in human hematopoietic cell lines SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE HL60 cells; PMA; Interleukin-1 alpha; gene expression ID HUMAN ADENOSINE-DEAMINASE; MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; LONG-TERM HEMATOPOIESIS; STEM-CELLS; PERIPHERAL-BLOOD; HL-60 CELLS; AUTOLOGOUS TRANSPLANTATION; ONCOGENE EXPRESSION; RETINOIC ACID AB The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1), We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor, We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2), In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines, PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector, The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1 alpha. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status. C1 Natl Human Genome Res Inst, Lab Gene Transfer, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Somatix Therapy Corp, Alameda, CA USA. RP Bodine, DM (reprint author), Natl Human Genome Res Inst, Lab Gene Transfer, Hematopoiesis Sect, NIH, 49 Convent Dr,Bldg 49,Rm 3A14 MSC 4442, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov NR 48 TC 41 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 EI 1096-0961 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD DEC 15 PY 1997 VL 23 IS 23 BP 422 EP 433 DI 10.1006/bcmd.1997.0161 PG 12 WC Hematology SC Hematology GA YM549 UT WOS:000071075900001 PM 9454686 ER PT J AU Kohn, EC AF Kohn, EC TI Angiogenesis in ovarian carcinoma - A formidable biomarker SO CANCER LA English DT Editorial Material ID TUMOR ANGIOGENESIS; BREAST-CARCINOMA; GROWTH-FACTOR; RECEPTORS RP Kohn, EC (reprint author), NCI,PATHOL LAB,10 CTR DR,MSC 1500,ROOM 2A33,BETHESDA,MD 20892, USA. NR 14 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1997 VL 80 IS 12 BP 2219 EP 2221 DI 10.1002/(SICI)1097-0142(19971215)80:12<2219::AID-CNCR1>3.0.CO;2-P PG 3 WC Oncology SC Oncology GA YK934 UT WOS:A1997YK93400001 PM 9404697 ER PT J AU Larson, SM El-Shirbiny, AM Divgi, CR Sgouros, G Finn, RD Tschmelitsch, J Picon, A Whitlow, M Schlom, J Zhang, JJ Cohen, AM AF Larson, SM El-Shirbiny, AM Divgi, CR Sgouros, G Finn, RD Tschmelitsch, J Picon, A Whitlow, M Schlom, J Zhang, JJ Cohen, AM TI Single chain antigen binding protein (sFv CC49) - First human studies in colorectal carcinoma metastatic to liver SO CANCER LA English DT Article; Proceedings Paper CT 6th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 10-12, 1996 CL PRINCETON, NJ SP NIH NCI, Ctr Molec Med & Immunol, Garden State Canc Ctr DE sFv CC49; colorectal carcinoma; metastatic; liver; intravenous injection ID MONOCLONAL-ANTIBODIES; FV; BIODISTRIBUTION; MELANOMA AB BACKGROUND. An sFv fragment of the anti-TAG-72 monoclonal antibody CC49 has been developed and has shown promise in improved targeting to colorectal carcinoma in animal studies. In this study the authors report their initial experience in human patients after intravenous injection. METHODS. Five patients with colorectal carcinoma metastatic to the liver were studied prior to surgery. High performance liquid chromatography showed a low level of aggregation (< 10% complex formation), before and after radiolabeling with iodogen. Prior to radiolabeling, (123)I was brought to the dry form, phosphate buffer added and titrated to a pH of 7, with diluted hydrochloric acid. (123)I was injected in doses of 26, 12, 27, 25 and 1 millicurie, respectively, and labeled to a 5-mg fragment. Single photon emission computed tomography and whole body imaging were performed at 4-6 hours, and 24 hours, respectively, after injection. RESULTS. The agent was rapidly cleared from the blood with biphasic clearance T-1/2 of 30 minutes and 10.5 hours, respectively Distribution from whole body imaging confirmed rapid equilibration with extracellular fluid, and clearance T-1/2 from the body was comparable to the slower component of blood clearance. The spleen was visualized in all patients, and the testes were imaged in 67% of male patients. Renal excretion was noted with early uptake and clearance from the renal parenchyma except in one patient in whom renal parenchyma retention was intense. Although image quality was suboptimal, tumor was visualized in all five patients in both primary and metastatic lesions. At surgery, (16-24 hours postinjection), the tumor retained significant concentrations of the radiotracer, with metastatic tumor/normal liver ratios of approximately 1:5-3:1. No patient had any associated symptom or change in biochemical and hematopoietic status. CONCLUSIONS. This study showed that sFv is safe, tissue equilibration and clearance is rapid, and early, same-day imaging of the primary and metastatic tumors is feasible in patients colorectal carcinoma. Further studies are warranted to define a more optimal mass of sFv CC49 dose for tumor targeting. (C) 1997 American Cancer Society. C1 Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Enzon Inc, Piscataway, NJ USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Univ Innsbruck, A-6020 Innsbruck, Austria. RP Larson, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [2PO1CA33049-12A1, NCI-CM-97609] NR 14 TC 44 Z9 48 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 1997 VL 80 IS 12 SU S BP 2458 EP 2468 PG 11 WC Oncology SC Oncology GA YM158 UT WOS:000071035600017 PM 9406696 ER PT J AU Katayose, Y Kim, M Rakkar, ANS Li, ZW Cowan, KH Seth, P AF Katayose, Y Kim, M Rakkar, ANS Li, ZW Cowan, KH Seth, P TI Promoting apoptosis: A novel activity associated with the cyclin-dependent kinase inhibitor p27 SO CANCER RESEARCH LA English DT Article ID MICE LACKING; CELL-CYCLE; P27(KIP1); GROWTH; HYPERPLASIA AB p27(Kip1), a cyclin-dependent kinase inhibitor, is recognized as a negative regulator of the cell cycle. In this paper, we report that overexpression of p27(Kip1) triggers apoptosis in several different human cancer cell lines. Using a recombinant adenoviral vector that expresses p27(Kip1) (Adp27), we found that overexpression of p27(Kip1) in MDA-MB-231 breast cancer cells induces apoptosis that was seen by a number of different techniques, including flow cytometry and in situ terminal deoxgnucleotidyl transferase-mediated nick end labeling, flow cytometric assay for sub-G(1) population, and 4',6-diamindino-2-phenylindole staining. Cleavage of poly(ADP-ribose) polymerase and degradation of cyclin B1, events that are known to be associated with apoptosis, were also observed following overexpression of p27(Kip1). This is the first report indicating a role for p27(Kip1) in induction of apoptosis. C1 NCI, Med Breast Canc Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Seth, P (reprint author), NCI, Med Breast Canc Sect, Med Branch, Div Clin Sci,NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. RI Unno, Michiaki/A-8633-2010 OI Unno, Michiaki/0000-0002-2145-6416 NR 20 TC 293 Z9 317 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5441 EP 5445 PG 5 WC Oncology SC Oncology GA YL378 UT WOS:000070948600002 PM 9407946 ER PT J AU Zhuang, ZP Ezzat, SZ Vortmeyer, AO Weil, R Oldfield, EH Park, WS Pack, S Huang, S Agarwal, SK Guru, SC Manickam, P Debelenko, LV Kester, MB Olufemi, SE Heppner, C Crabtree, JS Burns, AL Spiegel, AM Marx, SJ Chandrasekharappa, SC Collins, FS Emmert-Buck, MR Liotta, LA Asa, SL Lubensky, IA AF Zhuang, ZP Ezzat, SZ Vortmeyer, AO Weil, R Oldfield, EH Park, WS Pack, S Huang, S Agarwal, SK Guru, SC Manickam, P Debelenko, LV Kester, MB Olufemi, SE Heppner, C Crabtree, JS Burns, AL Spiegel, AM Marx, SJ Chandrasekharappa, SC Collins, FS Emmert-Buck, MR Liotta, LA Asa, SL Lubensky, IA TI Mutations of the MEN1 tumor suppressor gene in pituitary tumors SO CANCER RESEARCH LA English DT Article ID RAS MUTATIONS; RETINOBLASTOMA GENE; ADENOMAS; HETEROZYGOSITY; METHYLATION; CARCINOMA; PROTEIN; ORIGIN; LOCUS AB Although pituitary adenomas are monoclonal proliferations, somatic mutations involving genes that govern cell proliferation or hormone production have been difficult to identify, The genetic etiology of most pituitary tumors, therefore, remains unknown. Pituitary adenomas can develop sporadically or as a part of multiple endocrine neoplasia type 1 (MEN1), Recently, the gene responsible for MEN1 was cloned, To elucidate the potential etiological role of the MEN1 gene in pituitary tumorigenesis, 39 sporadic pituitary adenomas from 38 patients and 1 pituitary adenoma from a familial MEN1 patient were examined for MEN1 gene mutations and allelic deletions, Four of 39 sporadic pituitary adenomas showed a deletion of one copy of the MEN1 gene, and a specific MEN1 gene mutation in the remaining gene copy was detected in 2 of these tumors, The corresponding germ-line sequence was normal in all sporadic cases, A specific MEN1 mutation was detected in a pituitary adenoma and corresponding germ-line DNA in a patient with familial MEN1. An allelic deletion of the remaining copy of the MEN1 gene was also found in the patient's tumor. Genetic alterations of the MEN1 gene represent a candidate pathogenetic mechanism of pituitary tumorigenesis, The data suggest that somatic MEN1 gene mutations and deletions play a causative role in the development of a subgroup of sporadic pituitary adenomas. C1 NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Lab Gene Transfer, NIH, Bethesda, MD 20892 USA. Univ Toronto, Wellesley Hosp, Dept Med, Toronto, ON M4Y 1Y3, Canada. Univ Toronto, Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada. RP Lubensky, IA (reprint author), NCI, Lab Pathol, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 32 TC 188 Z9 192 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5446 EP 5451 PG 6 WC Oncology SC Oncology GA YL378 UT WOS:000070948600003 PM 9407947 ER PT J AU Wattenberg, LW Wiedmann, TS Estensen, RD Zimmerman, CL Steele, VE Kelloff, GJ AF Wattenberg, LW Wiedmann, TS Estensen, RD Zimmerman, CL Steele, VE Kelloff, GJ TI Chemoprevention of pulmonary carcinogenesis by aerosolized budesonide in female A/J mice SO CANCER RESEARCH LA English DT Article ID INHALED GLUCOCORTICOIDS; LUNG; DEXAMETHASONE; INHIBITION; MYOINOSITOL; THERAPY; ASTHMA AB This investigation is part of a continuing effort to develop effective chemoprevention for carcinogenesis of the lung, The present study explores the use of aerosol administrations for this purpose, The agent selected for initial study was the synthetic glucocorticoid budesonide, This selection was based on previous work in which budesonide added to the diet was found to inhibit pulmonary adenoma formation in female A/J mice, However, high dose levels were required, i.e., of the order of 300 mu g/kg, of body weight [L. W. Wattenberg and R. D. Estensen, Carcinogenesis (Lond.), 18: 2015-2017, 1997]. For aerosol administration of budesonide, a nose-only technique has been developed that entails nebulization of the compound dissolved in ethanol and subsequent stripping off of the solvent (less than 3 mu l ethanol/liter of air remaining at the site of inhalation), The budesonide particles produced by the apparatus had a mass median aerodynamic diameter of less than 1 mu m. An experiment has been tarried out in which the inhibitory effects of aerosolized budesonide, given for I min sis times a week, were studied, Concentrations of budesonide of 26, 81, and 148 mu g/liter of air (calculated doses of 23, 72, and 126 mu g/kg of body weight) mere used, The aerosols were started 1 week after three oral administrations of benzo(a)pyrene (2 mg/20 g of body weight) to female A/J mice, All three doses of budesonide resulted in more than 80% inhibition of pulmonary tumor formation compared to the aerosol control and 90% or greater compared to mice not exposed to aerosol, The difference in inhibition is due to the aerosol procedure itself, which produces a reduction in tumor formation, A decrease in splenic weight (evidence of a systemic effect) occurred at all doses of budesonide, To the best of our knowledge, this is the first published effort at the use of aerosol administration to prevent neoplasia of the respiratory tract, The results of the present study show that administration of a potential chemopreventive agent by aerosol at a low dose can inhibit the occurrence of pulmonary carcinogenesis in female A/J mice. C1 Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Grad Studies Pharmaceut, Coll Pharm, Minneapolis, MN 55455 USA. NCI, Bethesda, MD 20892 USA. RP Wattenberg, LW (reprint author), Univ Minnesota, Dept Lab Med & Pathol, 6-133 Jackson Hall,321 Church St SE, Minneapolis, MN 55455 USA. FU NCI NIH HHS [N01-CN-55177] NR 24 TC 107 Z9 107 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5489 EP 5492 PG 4 WC Oncology SC Oncology GA YL378 UT WOS:000070948600012 PM 9407956 ER PT J AU Lavigne, JA Helzlsouer, KJ Huang, HY Strickland, PT Bell, DA Selmin, O Watson, MA Hoffman, S Comstock, GW Yager, JD AF Lavigne, JA Helzlsouer, KJ Huang, HY Strickland, PT Bell, DA Selmin, O Watson, MA Hoffman, S Comstock, GW Yager, JD TI An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer SO CANCER RESEARCH LA English DT Article ID ESTROGEN-INDUCED CARCINOGENESIS; HAMSTER-KIDNEY; GLUTATHIONE TRANSFERASES; LIPID-PEROXIDATION; REACTIVE OXYGEN; ESTRADIOL; DNA; 4-HYDROXYLATION; POLYMORPHISM; EXPRESSION AB Mounting evidence suggests that catechol metabolites of estradiol may contribute to the development of estrogen-induced cancers, O-Methylation, catalyzed by catechol-O-methyltransferase (COMT), inactivates catechol estrogens, COMT is polymorphic in the human population, with 25% of Caucasians being homozygous for a low activity allele of the enzyme (COMTLL). We hypothesized that tom activity COMT may be a risk factor for human breast cancer and designed a PCR-based RFLP assay to determine COMT genotype in a cohort of 112 matched, nested case-control samples, In the total study population, the odds ratios for the association of breast cancer risk with COMTHL and COMTLL genotypes were 1.30 [confidence interval (CI), 0.66-2.58] and 1.45 (CI, 0.69-3.07), respectively, Postmenopausal COMTLL women had a greater than 2-fold increased risk of developing breast cancer [odds ratio (OR), 2.18; CI, 0.93-5.11]. The association of COMTLL with the development of postmenopausal breast cancer was stronger and statistically significant in those women with a body mass index >24.47 kg/m(2) (OR, 3.58; CI, 1.07-11.98), When COMTLL was combined with either glutathione S-transferase (GST) M1 null or with GSTP1 Ile-105-Val/Val-105-Val (intermediate/low activity, respectively) genotypes, the risk for developing postmenopausal breast canter was also significantly increased, Our findings suggest that the allele encoding low activity COMT may be an important contributor to the postmenopausal development of breast cancer in certain women. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Environm & Occupat Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIEHS, Genet Risk Grp, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Yager, JD (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Room 7032,615 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [R01 CA62988, R03 CA70655]; NIEHS NIH HHS [T32 ES07141] NR 29 TC 219 Z9 224 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5493 EP 5497 PG 5 WC Oncology SC Oncology GA YL378 UT WOS:000070948600013 PM 9407957 ER PT J AU Bottinger, EP Jakubczak, JL Haines, DC Bagnall, K Wakefield, LM AF Bottinger, EP Jakubczak, JL Haines, DC Bagnall, K Wakefield, LM TI Transgenic mice overexpressing a dominant-negative mutant type II transforming growth factor beta receptor show enhanced tumorigenesis in the mammary gland and lung in response to the carcinogen 7,12-dimethylbenz-[alpha]-anthracene SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR ACTIVITY; TGF-BETA; CANCER-CELLS; GROWTH-FACTOR-BETA-1 TRANSGENE; EPITHELIAL-CELLS; EXPRESSION; GENE; TGF-BETA-1; INHIBITION; P53 AB To test the hypothesis that the transforming grow th factor-beta (TGF-beta) system has tumor suppressor activity in the mammary gland, we have generated transgenic mice overexpressing a dominant-negative mutant form of the type II TGF-beta receptor, under the control of the mouse mammary tumor virus-long terminal repeat, High-level expression of the transgene was observed in the mammary and salivary glands, with lower expression in the lung, spleen, and testis, Older nulliparous transgenic mice (9-17 months) showed a marked increase in the incidence and degree of lobulo-alveolar side-branching in the mammary glands when compared to wild-type littermates (24.8% of glands examined histologically versus 14.4%; P = 0.004), suggesting a role for endogenous TGF-beta s in regulating development or maintenance of mammary alveoli, Spontaneous tumorigenesis was unchanged in the transgenic mice, However, following initiation with the carcinogen 7,12-dimethylbenz[a]anthracene, the transgenic group showed a significant increase in the incidence and multiplicity of mammary tumors when compared with wild-type littermates (40% incidence in transgenic mice versus 22% for wild-type, with 4 of 25 transgenics developing multiple mammary tumors versus 0 of 27 wild-type; P = 0.03), An early increase in the incidence of lung tumors was also observed in transgenic mice, but no difference between genotype groups was seen in the incidence of tumors in tissues in which the transgene is not expressed, The data show that the endogenous TGF-beta system has tumor suppressor activity in the mammary gland and lung. C1 NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wakefield, LM (reprint author), NCI, Chemoprevent Lab, Bldg 41,Room 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 48 TC 153 Z9 164 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5564 EP 5570 PG 7 WC Oncology SC Oncology GA YL378 UT WOS:000070948600024 PM 9407968 ER PT J AU Sausville, EA AF Sausville, EA TI The tyrphostin AG17 induces apoptosis and inhibition of cdk2 activity in a lymphoma cell line that overexpresses bcl-2 SO CANCER RESEARCH LA English DT Letter C1 NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1997 VL 57 IS 24 BP 5610 EP 5610 PG 1 WC Oncology SC Oncology GA YL378 UT WOS:000070948600031 PM 9407975 ER PT J AU Abrams, SI Khleif, SN Bergmann-Leitner, ES Kantor, JA Chung, Y Hamilton, JM Schlom, J AF Abrams, SI Khleif, SN Bergmann-Leitner, ES Kantor, JA Chung, Y Hamilton, JM Schlom, J TI Generation of stable CD4(+) and CD8(+) T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations SO CELLULAR IMMUNOLOGY LA English DT Article ID PANCREATIC-CARCINOMA PATIENTS; P21 RAS; CLASS-I; OVERLAPPING EPITOPES; LYMPHOCYTES-T; GENE FAMILY; RESPONSES; INDUCTION; CANCER; IDENTIFICATION AB Previous studies have identified and characterized both murine in vivo and human in vitro T cell responses reflecting specific mutations in the ras protooncogenes at codon 12, 13, or 61. In an attempt to determine whether peptide epitopes reflecting point mutations in the ras oncogenes are immunogenic in humans for the production of CD4(+) and/or CD8(+) T cell responses, a phase I clinical trial was initiated in metastatic carcinoma patients whose primary tumors harbor mutations in the K-ras proto oncogenes at codon 12. The peptides used here as immunogens, which were administered in Deter adjuvant, spanned the ras sequence 5-17 and reflected the amino acid substitution of glycine (Gly) at position 12 to aspartic acid (Asp), cysteine (Cys), or valine (Val). Three of eight evaluable patients have demonstrated peptide-specific cell-mediated immunity, as determined by the production of T cell lines resulting from the vaccination. First, an antigen (Ag)-specific, major histocompatibility complex (MHC) class II (DP)-restricted CD4(+) T cell line was established in vitro from postvaccination lymphocytes of a non-small cell lung carcinoma patient whose primary tumor contained a Cys12 mutation when cultured on the immunizing peptide. Moreover, CD4(+) proliferation was inducible against the corresponding mutant K-ras protein, suggesting productive T cell receptor recognition of exogenously processed Ag. Second, an Ag-specific, MHC class I (HLA-A2)-restricted CD8(+) cytotoxic T lymphocyte (CTL) line was established in vitro from postvaccination lymphocytes of a colon carcinoma patient whose primary tumor contained an Asp12 mutation. To that end, a 10-mer peptide, nested within the 13-mer immunizing peptide, was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo primed CD8(+) CTL precursors. Third, both Ag-specific, MHC class II (DQ)restricted CD4(+) and MHC class I-restricted (HLA-A2) CD8(+) T cell lines were generated from a single patient with duodenal carcinoma whose primary tumor contained a Val12 mutation when cultured on the immunizing 13-mer peptide or a nested 10-mer peptide [i.e., ras5-14(Val12)], respectively. Evidence is thus provided that vaccination with mutant ras oncogene peptides in adjuvant may induce specific anti-ras cellular immune responses, with no detectable cross-reactivity toward normal proto ras sequences. Moreover, we have identified for the first time human HLA-A2-restricted, CD8(+) CTL epitopes reflecting specific point mutations in the K-ras oncogenes at codon 12 which, in concert with the activation of the CD4(+) T cell response, may have important implications for both active and passive immunotherapies in selected cancer patients. (C) 1997 Academic Press. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Rm 8B07,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 40 TC 52 Z9 53 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 1997 VL 182 IS 2 BP 137 EP 151 DI 10.1006/cimm.1997.1224 PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA ZC945 UT WOS:000072634900007 PM 9514698 ER PT J AU Gopinath, R Nutman, TB AF Gopinath, R Nutman, TB TI Identification of eosinophils in lysed whole blood using side scatter and CD16 negativity SO CYTOMETRY LA English DT Article DE CD16 negativity; eosinophils; gate; side scatter; whole blood ID GAMMA-RIII CD16; FLOW-CYTOMETRY; EXPRESSION; NEUTROPHILS AB The identification of eosinophils in lysed whole blood by flow cytometry can be problematic, since these cells overlap significantly with the neutrophil cluster on forward scatter versus side scatter plots of whole blood samples. Current methods can be time-consuming when running multiple samples or may compromise yield in the interests of greater accuracy. The use of eosinophil purification techniques prior to FAGS analysis or sorting as a way of ensuring purity may have unpredictable effects on eosinophil activation, leading to questionable data interpretation. Here we describe a simple, single-step method for definition of eosinophils utilizing their high side scatter and CD16 fluorescence negativity to differentiate them from neutrophils. The purity of the neutrophil and eosinophil populations sorted with this gate is close to 100% regardless of the peripheral blood eosinophil count, while the population obtained by sorting on a plot of FSC/SSC was a mixture of eosinophils and neutrophils. We suggest this method as a simple, reproducible, and accurate way of defining eosinophils by flow cytometry for analysis or sorting. (C) 1997 Wiley-Liss, Inc. C1 NIAID, NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Gopinath, R (reprint author), NIAID, NIH, Helminth Immunol Sect, Parasit Dis Lab, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 9 TC 27 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1997 VL 30 IS 6 BP 313 EP 316 PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YN962 UT WOS:000071226300006 PM 9440823 ER PT J AU Fleisher, TA Marti, G AF Fleisher, TA Marti, G TI No wash step required - Authors' response SO CYTOMETRY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1997 VL 30 IS 6 BP 324 EP 325 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YN962 UT WOS:000071226300009 ER PT J AU Rausa, F Samadani, U Ye, HG Lim, L Fletcher, CF Jenkins, NA Copeland, NG Costa, RH AF Rausa, F Samadani, U Ye, HG Lim, L Fletcher, CF Jenkins, NA Copeland, NG Costa, RH TI The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3 beta in the developing murine liver and pancreas SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-3-BETA; SURFACTANT PROTEIN-B; FORK-HEAD; MOUSE EMBRYO; DEFINITIVE ENDODERM; INSULIN GENE; LINKAGE MAP; BETA-CELLS; EXPRESSION; TISSUE AB Murine hepatocyte nuclear factor-3 beta (HNF-3 beta) protein is a member of a large family of developmentally regulated transcription factors that share homology in the winged helix/fork head DNA binding domain and that participate in embryonic pattern formation. HNF-3 beta also mediates cell-specific transcription of genes important for the function of hepatocytes, intestinal and bronchiolar epithelial, and pancreatic acinar cells. We have previously identified a liver-enriched transcription factor, HNF-6, which is required for HNF-3 beta promoter activity and also recognizes the regulatory region of numerous hepatocyte-specific genes. In this study we used the yeast one-hybrid system to isolate the HNF-6 cDNA, which encodes a cut-homeodomain-containing transcription factor that binds with the same specificity as the liver HNF-6 protein. Cotransfection assays demonstrate that HNF-6 activates expression of a reporter gene driven by the HNF-6 binding site from either the HNF-3 beta or transthyretin (TTR) promoter regions. We used interspecific backcross analysis to determine that murine Hnf6 gene is located in the middle of mouse chromosome 9. In situ hybridization studies of staged specific embryos demonstrate that HNF-6 and its potential target gene, HNF-3 beta, are coexpressed in the pancreatic and hepatic diverticulum. More detailed analysis of HNF-6 and HNF-3 beta's developmental expression patterns provides evidence of colocalization in hepatocytes, intestinal epithelial, and in the pancreatic ductal epithelial and exocrine acinar cells. The expression patterns of these two transcription factors do not overlap in other endoderm-derived tissues or the neurotube. We also found that HNF-6 is also abundantly expressed in the dorsal root ganglia, the marginal layer, and the midbrain. At day 18 of gestation and in the adult pancreas, HNF-6 and HNF-3 beta transcripts colocalize in the exocrine acinar cells, but their expression patterns diverge in other pancreatic epithelium. HNF-6, but not HNF-3 beta, expression continues in the pancreatic ductal epithelium, whereas only HNF-3 beta becomes restricted to the endocrine cells of the islets of Langerhans. We discuss these expression patterns with respect to specification of hepatocytes and differentiation of the endocrine and exocrine pancreas. (C) 1997 Academic Press. C1 Univ Illinois, Coll Med, Dept Biochem & Mol Biol MC 536, Chicago, IL 60612 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Costa, RH (reprint author), Univ Illinois, Coll Med, Dept Biochem & Mol Biol MC 536, 1819 W Polk St, Chicago, IL 60612 USA. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [R01 GM43241-08] NR 63 TC 144 Z9 145 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 1997 VL 192 IS 2 BP 228 EP 246 DI 10.1006/dbio.1997.8744 PG 19 WC Developmental Biology SC Developmental Biology GA YR140 UT WOS:000071464100003 PM 9441664 ER PT J AU Glasgow, E Karavanov, AA Dawid, IB AF Glasgow, E Karavanov, AA Dawid, IB TI Neuronal and neuroendocrine expression of lim3, a LIM class homeobox gene, is altered in mutant zebrafish with axial signaling defects SO DEVELOPMENTAL BIOLOGY LA English DT Article DE pituitary; pineal; spinal cord; development; transcription factors ID CENTRAL-NERVOUS-SYSTEM; FLOOR PLATE CELLS; EMBRYONIC ZEBRAFISH; SPINAL-CORD; CHROMOSOMAL LOCALIZATION; BRACHYDANIO-RERIO; AXONAL OUTGROWTH; MOTOR-NEURONS; GROWTH CONE; BRAIN AB LIM class homeobox genes code for a family of transcriptional regulators that encode important determinants of cell lineage and cell type specificity. The lim3 gene from the zebrafish, Danio rerio, is highly conserved in sequence and expression pattern compared to its homologs in other vertebrates. In this paper we report immunocytochemical analysis of Lim3 protein expression in the pituitary, pineal, hindbrain, and spinal cord of the embryo, revealing an asymmetrical, lateral and late program of pituitary development in zebrafish, distinct from the pattern in other vertebrates. We studied Lim3 expression in no rail, floating head, and cyclops mutant embryos, all of which have midline defects, with special reference to spinal cord differentiation where Lim3 marks mostly motoneurons. cyclops embryos showed essentially normal Lim3 expression in the hindbrain and spinal cord despite the absence of the floor plate, while no rail mutant embryos, which lack a differentiated notochord, displayed an excess of Lim3-expressing cells in a generally normal pattern. In contrast, Lim3-positive cells largely disappeared from the posterior spinal cord in floating head mutants, except in patches that correlated with remnants of apparent floor plate cells. These results support the view that either notochord or floor plate signaling can specify Lim3-positive motoneurons in the spinal cord. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Room 413, Bethesda, MD 20892 USA. OI Glasgow, Eric/0000-0001-7729-3954 NR 69 TC 69 Z9 70 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 1997 VL 192 IS 2 BP 405 EP 419 DI 10.1006/dbio.1997.8761 PG 15 WC Developmental Biology SC Developmental Biology GA YR140 UT WOS:000071464100016 PM 9441677 ER PT J AU Sparenborg, S Vocci, F Zukin, S AF Sparenborg, S Vocci, F Zukin, S TI Peripheral cocaine-blocking agents: new medications for cocaine dependence - An introduction to immunological and enzymatic approaches to treating cocaine dependence reported by Fox, Gorelick and Cohen in the immediately succeeding articles (see pages 153-174) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE enzyme; vaccine; butyrylcholinesterase; catalytic antibodies; medical treatment C1 Natl Inst Drug Abuse, Medicat Dev Div, NIH, Rockville, MD 20857 USA. Natl Inst Drug Abuse, Div Clin & Serv Res, NIH, Rockville, MD 20857 USA. RP Sparenborg, S (reprint author), Natl Inst Drug Abuse, Medicat Dev Div, NIH, Room 11A-55,5600 Fishers Lane, Rockville, MD 20857 USA. NR 3 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 15 PY 1997 VL 48 IS 3 BP 149 EP 151 DI 10.1016/S0376-8716(97)00072-0 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YM892 UT WOS:000071112200002 PM 9449012 ER PT J AU Gorelick, DA AF Gorelick, DA TI Enhancing cocaine metabolism with butyrylcholinesterase as a treatment strategy SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 27th Annual Medical-Scientific Conference of the American-Society-of-Addiction-Medicine CY APR, 1996 CL ATLANTA, GA SP Amer Soc Addict Med DE cocaine; butyrylcholinesterase; pharmacokinetics; metabolites ID ATYPICAL PLASMA CHOLINESTERASE; PRETREATMENT DRUGS; TOXICITY; RATS; PROTECTION; HYDROLYSIS; LIVER; MICE; ACETYLCHOLINESTERASE; PSEUDOCHOLINESTERASE AB Existing pharmacodynamic approaches to cocaine abuse treatment have not been widely successful. An alternative, pharmacokinetic, approach is to enhance cocaine metabolism by administration of butyrylcholinesterase (BChE), a major cocaine-metabolizing enzyme in primates. Initial studies in rodents suggest that BChE pretreatment can substantially reduce the acute physiological and behavioral effects of cocaine, at enzyme doses that themselves have no behavioral or toxic effects. A single enzyme injection may increase plasma BChE activity for several days, suggesting that exogenous administration may be practical. BChE treatment may also produce a favorable pattern of cocaine metabolites. Further research is needed to evaluate the long-term effects of BChE administration. (C) 1997 Elsevier Science Ireland Ltd. C1 NIDA, NIH, Div Intramural Res, Treatment Branch, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, NIH, Div Intramural Res, Treatment Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 60 TC 98 Z9 98 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 15 PY 1997 VL 48 IS 3 BP 159 EP 165 DI 10.1016/S0376-8716(97)00119-1 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YM892 UT WOS:000071112200004 PM 9449014 ER PT J AU Cohen, PJ AF Cohen, PJ TI Immunization for prevention and treatment of cocaine abuse: legal and ethical implications SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 27th Annual Medical-Scientific Conference of the American-Society-of-Addiction-Medicine CY APR, 1996 CL ATLANTA, GEORGIA SP Amer Soc Addict Med DE cocaine vaccine; addiction therapy; stigmatization and discrimination; privacy and confidentiality; law and ethics ID COMPULSORY TREATMENT; ADDICTION; INTOXICATION; MECHANISMS; FRAGMENTS; PRIVACY AB A cocaine vaccine, currently under investigation by several laboratories, would be an innovative and exciting means of treating and preventing cocaine addiction. However, an approved vaccine will raise at least two major areas of concern. (1) Loss of privacy: cocaine antibodies might be used as a marker to identify, penalize, and stigmatize vaccinated individuals. (2) Selection for vaccination: should immunization be voluntary or compelled; should immunization be restricted to addicts, to those at risk of addiction, or should it be universal; should immunization be used in children? I propose to analogize cocaine addiction to an infectious disease which poses a major public health problem. This approach can provide an ethical and legal foundation on which we may begin to formulate a societal approach to the use of the cocaine vaccine. (C) 1997 Elsevier Science Ireland Ltd. C1 Natl Inst Drug Abuse, Medicat Dev Div, NIH, Rockville, MD USA. RP Cohen, PJ (reprint author), Natl Inst Drug Abuse, Medicat Dev Div, NIH, Rockville, MD USA. NR 29 TC 15 Z9 15 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 15 PY 1997 VL 48 IS 3 BP 167 EP 174 DI 10.1016/S0376-8716(97)00075-6 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YM892 UT WOS:000071112200005 PM 9449015 ER PT J AU Gadbut, AP Wu, LY Tang, DJ Papageorge, A Watson, JA Galper, JB AF Gadbut, AP Wu, LY Tang, DJ Papageorge, A Watson, JA Galper, JB TI Induction of the cholesterol metabolic pathway regulates the farnesylation of RAS in embryonic chick heart cells: a new role for Ras in regulating the expression of muscarinic receptors and G proteins SO EMBO JOURNAL LA English DT Article DE cholesterol; farnesylation; G protein; heart cells; Ras ID LOW-DENSITY LIPOPROTEINS; NEURONAL DIFFERENTIATION; ATRIAL CELLS; PC12 CELLS; KINASE-C; FARNESYLTRANSFERASE; GENE; PHOSPHORYLATION; RESPONSIVENESS; ISOPRENYLATION AB We propose a novel mechanism for the regulation of the processing of Ras and demonstrate a new function for Ras in regulating the expression of cardiac autonomic receptors and their associated G proteins, We have demonstrated previously that induction of endogenous cholesterol synthesis in cultured cardiac myocytes resulted in a coordinated increase in expression of muscarinic receptors, the G protein alpha-subunit, G-alpha(i2), and the inward rectifying K+ channel, GIRK1, These changes in gene expression were associated with a marked increase in the response of heart cells to parasympathetic stimulation, In this study, we demonstrate that the induction of the cholesterol metabolic pathway regulates Ras processing and that Ras regulates expression of G-alpha(i2), We show that in primary cultured myocytes most of the RAS is localized to the cytoplasm in an unfarnesylated form, Induction of the cholesterol metabolic pathway results in increased farnesylation and membrane association of RAS, Studies of Ras mutants expressed in cultured heart cells demonstrate that activation of Ras by induction of the cholesterol metabolic pathway results in increased expression of G-alpha(i2) mRNA, Hence farnesylation of Ras is a regulatable process that plays a novel role in the control of second messenger pathways. C1 Harvard Univ, Sch Med, Dept Med, Cardiovasc Div,Brigham & Womens Hosp, Boston, MA 02215 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Galper, JB (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiovasc Div,Brigham & Womens Hosp, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL36014, R01 HL036014, HL08463] NR 47 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1997 VL 16 IS 24 BP 7250 EP 7260 DI 10.1093/emboj/16.24.7250 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YP611 UT WOS:000071295500004 PM 9405354 ER PT J AU Fazioli, F Resnati, M Sidenius, N Higashimoto, Y Appella, E Blasi, F AF Fazioli, F Resnati, M Sidenius, N Higashimoto, Y Appella, E Blasi, F TI A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity SO EMBO JOURNAL LA English DT Article DE chemotaxis; G protein; pertussis toxin; receptor; urokinase-type plasminogen activator ID PLASMINOGEN-ACTIVATOR RECEPTOR; LIGAND-BINDING DOMAIN; CELL-SURFACE RECEPTOR; BREAST-CANCER; T-LYMPHOCYTES; INDUCTION; MICE; EXPRESSION; MONOCYTES; CLONING AB The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR/CD87) in cell migration and invasion is well substantiated, Recently, uPA has been shown to be essential in cell migration, since uPA(-/-) mice are greatly impaired in inflammatory cell recruitment, We have shown previously that the uPA-induced chemotaxis requires interaction with and modification of uPAR/CD87, which is the true chemoattracting molecule acting through an unidentified cell surface component which mediates this cell surface chemokine activity, By expressing and testing several uPAR/CD87 variants, we have located and functionally characterized a potent uPAR/CD87 epitope that mimics the effects of the uPA-uPAR interaction, The chemotactic activity lies in the region linking domains 1 and 2, the only protease-sensitive region of uPAR/CD87, efficiently cleaved by uPA at physiological concentrations. Synthetic peptides carrying this epitope promote chemotaxis and activate p56/p59(hck) tyrosine kinase. Both chemotaxis and kinase activation are pertussis toxin sensitive, involving a G(i/o) protein in the pathway. C1 San Raffaele Sci Inst, DIBIT, Dept Biochem & Biotechnol, I-20132 Milan, Italy. Univ Milan, Dept Genet & Microbial Biol, I-20133 Milan, Italy. NIH, Cell Biol Lab, NCI, Bethesda, MD 20892 USA. RP Blasi, F (reprint author), San Raffaele Sci Inst, DIBIT, Dept Biochem & Biotechnol, Via Olgettina 60, I-20132 Milan, Italy. RI Sidenius, Nicolai/M-9643-2015 OI Sidenius, Nicolai/0000-0002-7825-7629 NR 40 TC 195 Z9 200 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1997 VL 16 IS 24 BP 7279 EP 7286 DI 10.1093/emboj/16.24.7279 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YP611 UT WOS:000071295500007 PM 9405357 ER PT J AU Wei, SQ Mizuuchi, K Craigie, R AF Wei, SQ Mizuuchi, K Craigie, R TI A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration SO EMBO JOURNAL LA English DT Article DE DNA transposition; footprinting; PCR; pre-integration complexes; retrovirus ID IMMUNODEFICIENCY-VIRUS INTEGRATION; HIV-1 INTEGRASE; CONCERTED INTEGRATION; CATALYTIC DOMAIN; ESCHERICHIA-COLI; BINDING DOMAIN; IN-VITRO; POL GENE; PROTEIN; INVITRO AB We have probed the nucleoprotein organization of Moloney murine leukemia virus (MLV) pre-integration complexes using a novel footprinting technique that utilizes a simplified in vitro phage Mu transposition system, We find that several hundred base pairs at each end of the viral DNA are organized in a large nucleoprotein complex, which we call the intasome, This structure is not-formed when pre-integration complexes are made by infecting cells with integrase-minus virus, demonstrating a requirement for integrase. In contrast, footprinting of internal regions of the viral DNA did not reveal significant differences between pre-integration complexes with and without integrase. Treatment with high salt disrupts the intasome in parallel with loss of intermolecular integration activity. We show that a cellular factor is required for reconstitution of the intasome. Finally, we demonstrate that DNA-protein interactions involving extensive regions at the ends of the viral DNA are functionally important for retroviral DNA integration activity, Current in vitro integration systems utilizing purified integrase lack the full fidelity of the in vivo reaction, Our results indicate that both host factors and long viral DNA substrates may be required to reconstitute an in vitro system with all the hallmarks of DNA integration in vivo. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 46 TC 73 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1997 VL 16 IS 24 BP 7511 EP 7520 DI 10.1093/emboj/16.24.7511 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YP611 UT WOS:000071295500029 PM 9405379 ER PT J AU Schumacher, S Clubb, RT Cai, ML Mizuuchi, K Clore, GM Gronenborn, AM AF Schumacher, S Clubb, RT Cai, ML Mizuuchi, K Clore, GM Gronenborn, AM TI Solution structure of the Mu end DNA-binding I beta subdomain of phage Mu transposase: modular DNA recognition by two tethered domains SO EMBO JOURNAL LA English DT Article DE I beta domain; MuA transposase; NMR; protein-DNA interaction; solution structure ID PROTEIN-STRUCTURE DETERMINATION; NUCLEAR-MAGNETIC-RESONANCE; CRYSTAL-STRUCTURE; BACTERIOPHAGE-MU; STRAND TRANSFER; DIRECT REFINEMENT; CATALYTIC DOMAIN; CHEMICAL-SHIFTS; B-PROTEIN; C-ALPHA AB The phage Mu transposase (MuA) binds to the ends of the Mu genome during the assembly of higher order nucleoprotein complexes, me investigate the structure and function of the MuA end-binding domain (I beta gamma), The three-dimensional solution structure of the I beta subdomain (residues 77-174) has been determined using multidimensional NMR spectroscopy, It comprises five alpha-helices, including a helix-turn-helix (HTH) DNA-binding moth formed by helices 3 and 4, and can be subdivided into two interacting structural elements, The structure has an elongated disc-like appearance from which protrudes the recognition helix of the HTH moth, The topology of helices 2-4 is very similar to that of helices 1-3 of the previously determined solution structure of the MuA I gamma subdomain and to that of the homeodomain family of HTH DNA-binding proteins, We show that each of the two subdomains binds to one half of the 22 bp recognition sequence, I beta to the more conserved Mu end distal half (beta subsite) and I gamma to the Mu end proximal half (gamma subsite) of the consensus Mu end-binding site, The complete I beta gamma domain binds the recognition sequence with a 100-to 1000-fold higher affinity than the two subdomains independently, indicating a cooperative effect, Our results show that the Mu end DNA-binding domain of MuA has a modular organization, with each module acting on a specific Dart of the 22 bp binding site. Based on the present binding data and the structures of the I beta and I gamma subdomains, a model for the interaction of the complete I beta gamma domain with DNA is proposed. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM clore@vger.niddk.nih.gov; gronenborn@vger.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 62 TC 40 Z9 42 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1997 VL 16 IS 24 BP 7532 EP 7541 DI 10.1093/emboj/16.24.7532 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YP611 UT WOS:000071295500031 PM 9405381 ER PT J AU Khochbin, S Wolffe, AP AF Khochbin, S Wolffe, AP TI The origin and utility of histone deacetylases SO FEBS LETTERS LA English DT Article DE histone deacetylase; functional specificity; RPD3 family ID REPRESSION; COMPLEXES; PROTEIN; RPD3 AB A large region of two distinct yeast histone deacetylases, RPD3 and HDA1, is highly homologous to several prokaryotic enzymes that catalyze reactions involving various acetylated substrates, Proteins sharing this homology domain are found also in many higher eukaryotes and they all appear to be related to the RPD3 family of histone deacetylases. In each member of the family, the 'prokaryotic homology' domain covers almost two thirds of the protein, with the remaining portion containing the most divergent sequences. These sequences are located at the C-terminal region allowing for a clear definition of variants, Since the involvement of deacetylase members in different distinct regulatory complexes is now well established, the above observation suggests that the C-terminal domain may confer specificity to different members of the family, The RPD3 histone deacetylases thus appear as members of a family with a large conserved domain involved in enzymatic activity targeted to a short C-terminal domain, which probably confers functional specificity. The potential for deacetylases to be involved in multiple regulatory pathways provides an attractive counterpoint to the role of multiple histone acetyltransferases as coactivators. (C) 1997 Federation of European Biochemical Societies. C1 Fac Med, Inst Albert Bonniot, Lab Biol Mol Cycle Cellulaire, INSERM,U309, F-38706 La Tronche, France. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Khochbin, S (reprint author), Fac Med, Inst Albert Bonniot, Lab Biol Mol Cycle Cellulaire, INSERM,U309, Domaine Merci, F-38706 La Tronche, France. RI Khochbin, Saadi/M-8090-2013 NR 20 TC 36 Z9 36 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 15 PY 1997 VL 419 IS 2-3 BP 157 EP 160 DI 10.1016/S0014-5793(97)01423-3 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YM709 UT WOS:000071092900002 PM 9428625 ER PT J AU Kashuba, VI Gizatullin, RZ Protopopov, AI Allikmets, R Korolev, S Li, J Boldog, F Tory, K Zabarovska, V Marcsek, Z Sumegi, J Klein, G Zabarovsky, ER Kisselev, L AF Kashuba, VI Gizatullin, RZ Protopopov, AI Allikmets, R Korolev, S Li, J Boldog, F Tory, K Zabarovska, V Marcsek, Z Sumegi, J Klein, G Zabarovsky, ER Kisselev, L TI NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors SO FEBS LETTERS LA English DT Article DE gene mapping; cancer related gene; NotI linking clone; NotI jumping clone; (human chromosome 3) ID UBIQUITIN-SPECIFIC PROTEASE; ENTIRE LONG ARM; HUMAN GENOME; TRANSFERRIN RECEPTOR; LINKING CLONES; CPG ISLANDS; HUMAN-CHROMOSOME-3; CONSTRUCTION; MAP; HYBRIDIZATION AB By applying the 'recognition mask' strategy to 300 mammalian sequences containing NotI sites we demonstrated that 5' ends of genes are highly enriched in NotI sites, A NotI linking clone NL2-252 (D3S1678) containing transferrin receptor (TFRC) gene was used as an initial point for chromosomal jumping, One of the jumping clones, J21-045 traverses 210 kbp and links NL2-252 to NL26 (D3S1632), a NotI linking clone containing highly polymorphic sequences, The TFRC gene was mapped to 3q29, close to the telomeric marker D3S2344, by linkage analysis, a panel of hybrid cell lines, GeneBridge 4 panel and FISH, Clone NLM-007 (D3S4302) was found to contain ras-homologous gene RAB7, By FISH and a panel of hybrid cell lines this gene was mapped to 3q21, This region is of particular interest due to frequent rearrangements in different types of leukemia, Clone L2-081 (D3S4283) containing new member of ubiquitin-specific proteases (HAUSP gene) was localized in 3p21 inspiring further investigation of involvement of this gene in development of lung and renal carcinomas. (C) 1997 Federation of European Biochemical Societies. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 117984, Russia. Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine. Russian Acad Sci, Inst Cytol & Genet, Siberain Branch, Novosibirsk 630090, Russia. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Semmelweis Univ Med, Sch Med, Dept Mol Genet, H-1082 Budapest, Hungary. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Kisselev, L (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Vavilov Str 32, Moscow 117984, Russia. RI Zabarovsky, Eugene/A-6645-2010 NR 39 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 15 PY 1997 VL 419 IS 2-3 BP 181 EP 185 DI 10.1016/S0014-5793(97)01449-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YM709 UT WOS:000071092900007 PM 9428630 ER PT J AU Siliciano, JD Canman, CE Taya, Y Sakaguchi, K Appella, E Kastan, MB AF Siliciano, JD Canman, CE Taya, Y Sakaguchi, K Appella, E Kastan, MB TI DNA damage induces phosphorylation of the amino terminus of p53 SO GENES & DEVELOPMENT LA English DT Article DE p53; phosphorylation; ATM; genotoxic stress ID CYCLE CHECKPOINT PATHWAY; TUMOR-SUPPRESSOR PROTEIN; ATAXIA-TELANGIECTASIA; IN-VIVO; CELLULAR-RESPONSE; BINDING FUNCTION; GROWTH-FACTOR; KINASE-C; TRANSACTIVATION; ACTIVATION AB Data are presented demonstrating that DNA damage leads to specific post-translational modifications of p53 protein. Using two-dimensional peptide mapping of in vivo radiolabeled p53 tryptic phosphopeptides, recombinant truncated p53 protein, and synthetic p53 tryptic peptides, a unique p53 phosphopeptide was identified after exposure of ML-1 cells to ionizing irradiation. This peptide represents the first 24 amino acids of p53 and contains three phosphorylated serine residues. A specific p53 phosphopeptide antibody identified serine-15 as one of the two serines in p53 that becomes phosphorylated following DNA damage induced by either ionizing irradiation (IR) or ultraviolet (UV) irradiation in multiple cell types. IR-induced phosphorylation of p53 does not affect the kinetics of p53 binding to or dissociating from DNA as assessed by electrophoretic mobility-shift assays. However, p53 phosphorylation induced by DNA damage correlates with enhanced transcription of downstream p53 target genes. Low levels of phosphoserine-15 p53 are detectable within 6 hr after IR in AT cells, whereas lymphoblasts from normal individuals exhibit this modification within 1 hr. In contrast, phosphorylation of p53 on serine-15 is similar in normal and AT cells after UV irradiation. Our results indicate that p53 is phosphorylated in response to DNA damage, that this de novo phosphorylation may be involved in the subsequent induction and activation of p53, and that although ATM affects the kinetics of p53 phosphorylation after IR, it is not absolutely required for phosphorylation of p53 on serine-15. C1 Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 104, Japan. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Siliciano, JD (reprint author), Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA71387, R01 CA071387]; NIEHS NIH HHS [R01 ES005777, ES05777, R37 ES005777] NR 56 TC 627 Z9 633 U1 1 U2 15 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 1997 VL 11 IS 24 BP 3471 EP 3481 DI 10.1101/gad.11.24.3471 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YN804 UT WOS:000071209500017 PM 9407038 ER PT J AU Franzoso, G Carlson, L Xing, LP Poljak, L Shores, EW Brown, KD Leonardi, A Tran, T Boyce, BF Siebenlist, U AF Franzoso, G Carlson, L Xing, LP Poljak, L Shores, EW Brown, KD Leonardi, A Tran, T Boyce, BF Siebenlist, U TI Requirement for NF-kappa B in osteoclast and B-cell development SO GENES & DEVELOPMENT LA English DT Article DE NF-kappa B; knockout mice; osteopetrosis; B cell; development; osteoclasts ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; C-REL PROTOONCOGENE; MICE LACKING; TARGETED DISRUPTION; ONCOPROTEIN BCL-3; DENDRITIC CELLS; DEFICIENT MICE; MULTIORGAN INFLAMMATION; MONOCLONAL-ANTIBODIES AB NF-kappa B is a family of related, dimeric transcription factors that are readily activated in cells by signals associated with stress or pathogens. These factors are critical to host defense, as demonstrated previously with mice deficient in individual subunits of NF-kappa B. We have generated mice deficient in both the p50 and p52 subunits of NF-kappa B to reveal critical functions that may be shared by these two highly homologous proteins. We now demonstrate that unlike the respective single knockout mice, the p50/p52 double knockout mice fail to generate mature osteoclasts and B cells, apparently because of defects that track with these lineages in adoptive transfer experiments. Furthermore, these mice present markedly impaired thymic and splenic architectures and impaired macrophage functions. The blocks in osteoclast and B-cell maturation were unexpected. Lack of mature osteoclasts caused severe osteopetrosis, a family of diseases characterized by impaired osteoclastic bone resorption. These findings no iv establish critical roles for NF-kappa B in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-43510, R01 AR043510] NR 83 TC 666 Z9 688 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 1997 VL 11 IS 24 BP 3482 EP 3496 DI 10.1101/gad.11.24.3482 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YN804 UT WOS:000071209500018 PM 9407039 ER PT J AU Robertson, NG Skvorak, AB Yin, Y Weremowicz, S Johnson, KR Kovatch, KA Battey, JF Bieber, FR Morton, CC AF Robertson, NG Skvorak, AB Yin, Y Weremowicz, S Johnson, KR Kovatch, KA Battey, JF Bieber, FR Morton, CC TI Mapping and characterization of a novel cochlear gene in human and in mouse: A positional candidate gene for a deafness disorder, DFNA9 SO GENOMICS LA English DT Article ID SENSORINEURAL HEARING-LOSS; CARTILAGE MATRIX PROTEIN; HUMAN VONWILLEBRAND-FACTOR; TEMPORAL BONE FINDINGS; VON WILLEBRAND FACTOR; A-LIKE DOMAINS; EXTRACELLULAR-MATRIX; VII COLLAGEN; CDNA CLONING; CHAIN AB Previously we identified a partial human cDNA for a novel cochlear transcript, hCoch-5B2 (HGMW-approved symbol D14S564E), using subtractive hybridization techniques. Herein we report isolation and characterization of both human and mouse (D12H14S564E) cDNAs for Coch-5B2. Full-length Coch-5B2 deduced amino acid sequences reveal a very high degree of conservation in the coding region (89% nucleotide and 94% amino acid identity) and a potential signal peptide and two regions of extensive homology to the collagen-binding type A domains of von Willebrand factor, also present in other secreted proteins, including extracellular matrix components. High levels of hCoch-5B2 expression are seen only in human fetal inner ear structures, cochlea, and vestibule, among a large panel of human fetal and adult tissues. Coch-5B2 expression in the mouse is more widespread than in the human, with message detected in mouse adult spleen, cerebrum, cerebellum/medulla, and thymus. In both species very low level expression is detected in total eye. More specifically, mouse retina shows a higher level of mCoch-BB2 message than sclera and choroid. We have mapped hCoch-5B2 to human 14q11.2-q13 by somatic cell hybrid analysis and FISH and, more precisely, using radiation, hybrids to a region of markers linked to DFNA9, a nonsyndromic autosomal dominant sensorineural hearing loss with vestibular defects. Furthermore, we detect hCoch-5B2 on three overlapping YACs, two of which also contain one of the markers linked to DFNA9. mCoch-5B2 was genetically mapped in the mouse to chromosome 12, in a region of homologous synteny with human 14q11.2-q13, which contains the asp1 (audiogenic seizure prone) locus in the mouse. (C) 1997 Academic Press. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NIDCD NIH HHS [T32 DC00038, DC00871]; NIGMS NIH HHS [GM46697] NR 55 TC 97 Z9 104 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1997 VL 46 IS 3 BP 345 EP 354 DI 10.1006/geno.1997.5067 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YR074 UT WOS:000071455600004 PM 9441737 ER PT J AU Bergstein, I Eisenberg, LM Bhalerao, J Jenkins, NA Copeland, NG Osborne, MP Bowcock, AM Brown, AMC AF Bergstein, I Eisenberg, LM Bhalerao, J Jenkins, NA Copeland, NG Osborne, MP Bowcock, AM Brown, AMC TI Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is closely linked to WNT3 on human chromosome 17q121 SO GENOMICS LA English DT Article ID MAMMARY EPITHELIAL-CELLS; MOLECULAR-CLONING; PATTERN-FORMATION; MOUSE DEVELOPMENT; HUMAN GENOME; EXPRESSION; FAMILY; BREAST; DROSOPHILA; PROTEIN AB The Wnt gene family consists of at least 15 structurally related genes that encode secreted extracellular signaling factors. Wnt proteins function in a range of critical developmental processes in both vertebrates and invertebrates and are implicated in regulation of cell growth and differentiation in certain adult mammalian tissues, including the mammary gland. We have isolated a number of WNT sequences from human genomic DNA, two of which, designated WNT14 and WNT15, represent novel members of the Wnt gene family. We also isolated WNT sequences from human mammary cDNA and present evidence that WNT13 is expressed in human breast tissue, in addition to those previously described. WNT14 and WNT15 appear to have originated from an ancestral branch of the Wnt gene family that also includes the Wnt9 sequences found in jawless and cartilaginous fishes. A Wnt14 cDNA was also isolated from chicken and a partial Wnt15 sequence from mouse. We show that human WNT14 maps to chromosome 1 and that WNT15 maps distal to BRCA1 on chromosome 17q21, where it lies within 125 kb of another WNT family member, WNT3. (C) 1997 Academic Press. C1 Cornell Univ, Coll Med, Strang Cornell Canc Res Lab, New York, NY 10021 USA. Cornell Univ, Coll Med, Dept Cell Biol & Anat, New York, NY 10021 USA. Cornell Univ, Coll Med, Dept Surg, New York, NY 10021 USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX 75235 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL,Basic Res Program, Frederick, MD 21702 USA. RP Brown, AMC (reprint author), Cornell Univ, Coll Med, Strang Cornell Canc Res Lab, New York, NY 10021 USA. FU NCI NIH HHS [CA47207, CA60650, R01 CA047207] NR 52 TC 36 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1997 VL 46 IS 3 BP 450 EP 458 DI 10.1006/geno.1997.5041 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YR074 UT WOS:000071455600016 PM 9441749 ER PT J AU Darby, K Eyre, HJ Lapsys, N Copeland, NG Gilbert, DJ Couzens, M Antonova, O Sutherland, GR Jenkins, NA Herzog, H AF Darby, K Eyre, HJ Lapsys, N Copeland, NG Gilbert, DJ Couzens, M Antonova, O Sutherland, GR Jenkins, NA Herzog, H TI Assignment of the Y-4 receptor gene (PPYR1) to human chromosome 10q11.2 and mouse chromosome 14 SO GENOMICS LA English DT Article ID PANCREATIC-POLYPEPTIDE; NEUROPEPTIDE-Y; FUNCTIONAL EXPRESSION; PEPTIDE YY; CLONING; ORGANIZATION; FAMILY AB The human and mouse genes for the neuropeptide Y-4 receptor have been isolated, sequenced, and shown to contain no introns within the coding region of the gene. Nonisotopic in situ hybridization and interspecific mouse backcross mapping have localized the genes to human chromosome 10q11.2 and mouse chromosome 14. Five nucleotide variants, which do not alter the protein sequence, have been identified within the coding region of the human receptor gene. The human Y-4 subtype is most closely related to the Y-1-receptor subtype (42%), suggesting that it evolved from an ancestral Y-1-like receptor via an RNA-mediated transpositional event. (C) 1997 Academic Press. C1 St Vincents Hosp, Garvan Inst Med Res, Neurobiol Program, Sydney, NSW 2010, Australia. Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Ctr Med Genet, Adelaide, SA 5006, Australia. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Herzog, H (reprint author), St Vincents Hosp, Garvan Inst Med Res, Neurobiol Program, 384 Victoria St, Sydney, NSW 2010, Australia. RI Sutherland, Grant/D-2606-2012 NR 12 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1997 VL 46 IS 3 BP 513 EP 515 DI 10.1006/geno.1997.5071 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YR074 UT WOS:000071455600028 PM 9441761 ER PT J AU Leonard, JC Drwinga, HL Kim, CH Toji, LH Bender, PK Mulivor, RA Beck, JC AF Leonard, JC Drwinga, HL Kim, CH Toji, LH Bender, PK Mulivor, RA Beck, JC TI Regional mapping panels for chromosomes 3, 4, 5, 11, 15, 17, 18, and X SO GENOMICS LA English DT Article ID SOMATIC-CELL HYBRIDS; HUNTINGTON DISEASE GENE; SHORT ARM; TRANSLOCATION BREAKPOINTS; GENITOURINARY DYSPLASIA; INTERNATIONAL WORKSHOP; DELETION MAP; MARKERS; LOCALIZATION; ASSIGNMENT AB The NIGMS Human Genetic Mutant Cell Repository collects and distributes well-characterized human/rodent somatic cell hybrid regional mapping panels for human chromosomes 3, 4, 5, 11, 15, 17, 18, and X. Each regional mapping panel consists of 4 to 11 hybrids that divide the chromosome into 5 to 11 intervals. These panels have been extensively characterized by the submitters and the NIGMS Repository. (C) 1997 Academic Press. C1 Coriell Inst Med Res, Coriell Cell Repositories, NIGMS Human Genet Mutant Cell Repository, Camden, NJ 08103 USA. RP Beck, JC (reprint author), Coriell Inst Med Res, Coriell Cell Repositories, NIGMS Human Genet Mutant Cell Repository, Camden, NJ 08103 USA. FU NIGMS NIH HHS [N01-GM4-2102] NR 45 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1997 VL 46 IS 3 BP 530 EP 534 DI 10.1006/geno.1997.5047 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YR074 UT WOS:000071455600034 PM 9441767 ER PT J AU Su, Y Shi, YF Stolow, MA Shi, YB AF Su, Y Shi, YF Stolow, MA Shi, YB TI Thyroid hormone induces apoptosis in primary cell cultures of tadpole intestine: Cell type specificity and effects of extracellular matrix SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BINDING PROTEIN GENE; AMPHIBIAN METAMORPHOSIS; XENOPUS-LAEVIS; CONNECTIVE-TISSUE; RECEPTOR SUPERFAMILY; MOLECULAR MECHANISMS; SIGNAL-TRANSDUCTION; DEATH; EXPRESSION AB Thyroid hormone (T-3 or 3,5,3'-triiodothyronine) plays a causative role during amphibian metamorphosis. To investigate how T-3 induces some cells to die and others to proliferate and differentiate during this process, we have chosen the model system of intestinal remodeling, which involves apoptotic degeneration of larval epithelial cells and proliferation and differentiation of other cells, such as the fibroblasts and adult epithelial cells, to form the adult intestine. We have established in vitro culture conditions for intestinal epithelial cells and fibroblasts. With this system, we show that T-3 can enhance the proliferation of both cell types, However, T-3 also concurrently induces larval epithelial apoptosis, which can be inhibited by the extracellular matrix (ECM), Our studies with known inhibitors of mammalian cell death reveal both similarities and differences between amphibian and mammalian cell death. These, together with gene expression analysis, reveal that T-3 appears to simultaneously induce different pathways that lead to specific gene regulation, proliferation, and apoptotic degeneration of the epithelial cells, Thus, our data provide an important molecular and cellular basis for the differential responses of different cell types to the endogenous T-3 during metamorphosis and support a role of ECM during frog metamorphosis. C1 NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. RP Shi, YB (reprint author), NICHHD, Mol Embryol Lab, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 73 TC 47 Z9 47 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 15 PY 1997 VL 139 IS 6 BP 1533 EP 1543 DI 10.1083/jcb.139.6.1533 PG 11 WC Cell Biology SC Cell Biology GA YN243 UT WOS:000071147400016 PM 9396758 ER PT J AU Licinio, J Wong, ML AF Licinio, J Wong, ML TI Pathways and mechanisms for cytokine signaling of the central nervous system SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; MESSENGER-RNA; RAT-BRAIN; GENE-EXPRESSION; LOCALIZATION; ALPHA; MOUSE C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46, Bethesda, MD 20892 USA. RI Wong, Ma-Li/D-7903-2011; OI Licinio, Julio/0000-0001-6905-5884 NR 31 TC 159 Z9 162 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 15 PY 1997 VL 100 IS 12 BP 2941 EP 2947 DI 10.1172/JCI119846 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YN260 UT WOS:000071149100004 PM 9399938 ER PT J AU Fine, AE Ashton, FT Bhopale, VM Schad, GA AF Fine, AE Ashton, FT Bhopale, VM Schad, GA TI Sensory neuroanatomy of a skin-penetrating nematode parasite Strongyloides stercoralis .2. Labial and cephalic neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Caenorhabditis elegans; dendrite; mechanoreceptor; three-dimensional reconstructions; ultrastructure ID CAENORHABDITIS-ELEGANS; MECHANOSENSATION; MICROTUBULES; MICROSCOPY; RECEPTOR; TOUCH AB Host recognition, contact, and skin-penetration by Strongyloides stercoralis infective larvae are crucially import ant behavioral functions mediating transition from free-living to parasitic Life. The sensilla of the worm's anterior tip presumably play an important role in these processes, Besides the main chemosensilla, the amphids, which are of central importance, the larva has 16 putative mechanosensilla. There are six inner labial sensilla: two dorsal, two ventral, and two lateral. The two dorsal and ventral pairs are each innervated by two neurons, whereas each lateral sensillum is singly innervated. The six outer labial and four cephalic sensilla are all singly innervated. All of these have the characteristics of mechanoreceptors: they are closed to the external environment, and closely associated with the overlying cuticle. Distally, their dendritic processes contain granular material and associated microtubules. With two exceptions, the relevant neuronal cell bodies Lie in lateral ganglia adjacent to the nerve ring, their positions remarkably similar to those of their homologues in the free-living nematode, Caenorhabditis elegans. Cell bodies of two neuronal pairs, one of two dorsal inner labial neurons and one of two ventral inner labial neurons per side, are however, found far anterior to the remaining cell bodies. All labial and cephalic sensilla are apparently mechanoreceptors, complementing the well-developed chemosensilla. Presumably infective larvae require touch and stretch receptors, not only to initiate skin penetration by finding irregularities as points of access, but also to bore through tissue to reach their ultimate enteral destination. (C) 1997 Wiley-liss, Inc. C1 UNIV PENN,SCH VET MED,DEPT PATHOBIOL,PHILADELPHIA,PA 19104. UNIV PENN,NIH,IVEM IMAGE PROC RESOURCE,PHILADELPHIA,PA 19104. FU NCRR NIH HHS [RR 02483]; PHS HHS [R01 A1 22662] NR 29 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 15 PY 1997 VL 389 IS 2 BP 212 EP 223 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA YJ297 UT WOS:A1997YJ29700002 PM 9416917 ER PT J AU Prussin, C Foster, B AF Prussin, C Foster, B TI TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROMPTLY PRODUCE INTERLEUKIN-4; IMMUNOGLOBULIN-E PRODUCTION; CLASS-I MOLECULES; BETA-CHAIN; INTERFERON-GAMMA; THYMIC SELECTION; ALPHA-CHAIN; RECEPTOR; LYMPHOCYTES; EXPRESSION AB Murine NK1 natural T (NT) cells are a population of alpha beta T cells that express NK cell receptors and an invariant TCR rearrangement. These cells rapidly produce large amounts of IL-4 upon activation and have been suggested to promote Th2 differentiation. We sought to determine whether a human NK1 T cell analogue could be detected in PBMC, and if so, characterize the TCR usage, cytokine expression, and surface phenotype of this subset. Using flow cytometry, we have demonstrated a distinct population of V alpha 24(+), V beta 11(+), CD56(+) T cells consistent with NT cells. Upon sequencing these cells expressed an invariant V alpha 24-J alpha Q TCR rearrangement, verifying their identity as a human NK1 T cell analogue. NT cells demonstrated increased frequencies of both IFN-gamma and IL-4 production. Strikingly, 30 to 45% of CD4(+) NT cells expressed IL-4, a sixfold greater frequency than that seen in mainstream CD4(+) alpha beta T cells. Contrary to the pattern seen with mainstream T cells, virtually all IL-4-producing NT cells coexpressed IFN-gamma, indicating that this subset of NT cells has a unique Th0 phenotype. These data establish that V alpha 24(+) NT cells are a potent source of IL-4 and as such, may play a role in Th2 priming in human immune responses. This work demonstrates that human NT cells can be phenotypically identified and functionally studied in the blood of healthy or diseased subjects. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM calman@nih.gov OI Prussin, Calman/0000-0002-3917-3326 NR 48 TC 128 Z9 132 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1997 VL 159 IS 12 BP 5862 EP 5870 PG 9 WC Immunology SC Immunology GA YW264 UT WOS:000071914900015 PM 9550382 ER PT J AU Levine, BL Bernstein, WB Connors, M Craighead, N Lindsten, T Thompson, CB June, CH AF Levine, BL Bernstein, WB Connors, M Craighead, N Lindsten, T Thompson, CB June, CH TI Effects of CD28 costimulation on long-term proliferation of CD4(+) T cells in the absence of exogenous feeder cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; IN-VIVO; AUTOCRINE GROWTH; CLONAL EXPANSION; HIV-1 INFECTION; ACTIVATION; CTLA-4; INTERLEUKIN-2; EXPRESSION AB In this report, conditions for prolonged in vitro proliferation of polyclonal adult CD4(+) T cells via stimulation with immobilized anti-CD3 plus anti-CD28 have been established. CD4(+) cells maintained exponential growth for more than 60 days during which a total 10(9)- to 10(11)-fold expansion occurred. Cell cultures exhibited cyclical changes in cell volume, indicating that, in terms of proliferative rate, cells do not have to rest before restimulation. Indeed, electronic cell size analysis was the most reliable method to determine when to restimulate with additional immobilized mAb. The initial similar to 10(5)-fold expansion was autocrine, occurring in the absence of exogenous cytokines or feeder cells. Addition of recombinant human IL-2 after the initial autocrine expansion resulted in continued exponential proliferation. Phorbol ester plus ionomycin also induced long-term growth when combined with anti-CD28 stimulation. Analysis of the T cell repertoire after prolonged expansion revealed a diverse repertoire as assessed by anti-TCR V beta Abs or a PCR-based assay. Cytokines produced were consistent with maintenance of both Th1 and Th2 phenotypes; however, the mode of CD3 and CD28 stimulation could influence the cytokine secretion pattern. When anti-CD3 and anti-CD28 were immobilized on the same surface, ELISAs on culture supernatants revealed a pattern consistent with Th1 secretion. Northern analysis revealed that cytokine gene expression remained inducible. Spontaneous growth or cell transformation was not observed in more than 100 experiments. Together, these observations may have implications for gene therapy and adoptive immunotherapy. Furthermore, these culture conditions establish a model to study the finite lifespan of mature T lymphocytes. C1 USN, Med Res Inst, Immune Cell Biol Program, Bethesda, MD 20889 USA. Univ Chicago, Gwen Knapp Ctr, Chicago, IL 60637 USA. Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. NIAID, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Div Retrovirol, Rockville, MD 20850 USA. Henry M Jackson Fdn Advancement Mil Med, US Mil HIV Res Program, Bethesda, MD 20889 USA. RP Levine, BL (reprint author), USN, Med Res Inst, Immune Cell Biol Program, Mail Stop 061,8901 Wisconsin Ave, Bethesda, MD 20889 USA. RI Levine, Bruce/D-1688-2009 NR 59 TC 233 Z9 237 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1997 VL 159 IS 12 BP 5921 EP 5930 PG 10 WC Immunology SC Immunology GA YW264 UT WOS:000071914900022 PM 9550389 ER PT J AU Wofsy, C Torigoe, C Kent, UM Metzger, H Goldstein, B AF Wofsy, C Torigoe, C Kent, UM Metzger, H Goldstein, B TI Exploiting the difference between intrinsic and extrinsic kinases: Implications for regulation of signaling by immunoreceptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE KINASE; ACTIVATION MOTIF ITAM; FC-EPSILON-RI; IMMUNOGLOBULIN-E; MAST-CELLS; TRANSFECTED CELLS; BINDING; PHOSPHORYLATION AB When receptors must interact with an extrinsic kinase to initiate signaling, the kinase can play a regulatory role that is not available to intrinsic receptor kinases. Whether control is exercised at this level depends critically on the amount of kinase available to the receptors and on the potential for redistribution of the kinase during signaling. This study demonstrates that the high affinity receptor for IgE (Fc epsilon RI) on rat basophilic leukemia cells is regulated by its initiating kinase. We present a mathematical model that allows for the reversible recruitment of extrinsic kinases to phosphorylated immunoreceptor tyrosine-based activation motifs. By comparing model predictions to experimental time courses of phosphorylation, we infer that Lyn is limiting, that redistribution occurs after receptors are aggregated, and that the redistribution makes the relationship between tyrosine phosphorylation and receptor aggregation nonlinear. C1 Univ Calif Los Alamos Natl Lab, Div Theoret, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA. Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Goldstein, B (reprint author), Univ Calif Los Alamos Natl Lab, Div Theoret, Theoret Biol & Biophys Grp, T-10,MS K710, Los Alamos, NM 87545 USA. EM bxg@lanl.gov FU NIGMS NIH HHS [GM35556] NR 38 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1997 VL 159 IS 12 BP 5984 EP 5992 PG 9 WC Immunology SC Immunology GA YW264 UT WOS:000071914900029 PM 9550396 ER PT J AU Maurer, JA Wray, S AF Maurer, JA Wray, S TI Luteinizing hormone-releasing hormone (LHRH) neurons maintained in hypothalamic slice explant cultures exhibit a rapid LHRH mRNA turnover rate SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DRB; gene expression; GnRH; mRNA stability; organotypic; preoptic area ID MESSENGER-RIBONUCLEIC-ACID; GNRH GENE-EXPRESSION; VASOACTIVE INTESTINAL POLYPEPTIDE; ANTERIOR-PITUITARY GLAND; DAY-NIGHT VARIATION; PUSH-PULL CANNULAE; SUPRACHIASMATIC NUCLEUS; TYROSINE-HYDROXYLASE; PHORBOL ESTER; 3'-UNTRANSLATED REGION AB Evidence indicates that neuropeptide gene expression is tightly coupled to biosynthesis and secretion. Moreover, rhythmic gene expression often accompanies rhythmic secretion. Luteinizing hormone-releasing hormone (LHRH) neurosecretion, which regulates gonadal function, is pulsatile, with interpulse intervals of similar to 1 hr and pulse decays of <30 min in rats. As a basis for a rapid fall in peptide secretion, we hypothesize that LHRH mRNA levels rapidly decay. To address this hypothesis, we examined LHRH mRNA turnover in primary postnatal LHRH neurons maintained in long-term hypothalamic/preoptic area slice explant cultures, using in situ hybridization histochemistry (ISHH). Relative LHRH mRNA content per cell was quantitated by single-cell analysis after transcription inhibition with 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) or actinomycin D. Cultures were maintained in serum-free medium with tetrodotoxin to suppress spontaneous electrical activity and hence assess only intrinsic cellular activity. A plot of LHRH mRNA level per cell versus DRB treatment time showed a rapid initial decay of LHRH mRNA (t1/2, 5-13 min), followed by a slower decay rate (t1/2, 329-344 hr). LHRH cell number after drug treatment as determined by immunocytochemistry did not change. Comparison of mammalian LHRH mRNA 3'-untranslated regions showed two conserved regions. These data indicate that, in primary LHRH neurons, LHRH mRNA has an intrinsically high rate of turnover and a mRNA stabilization component. Foremost, decay of LHRH mRNA, the fastest reported for a neuropeptide to date, corresponds to the decay of LHRH peptide pulses. C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. OI wray, susan/0000-0001-7670-3915 NR 94 TC 30 Z9 30 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 1997 VL 17 IS 24 BP 9481 EP 9491 PG 11 WC Neurosciences SC Neurosciences & Neurology GA YK822 UT WOS:A1997YK82200010 PM 9391004 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Inhibition of ATP-activated current by zinc in dorsal root ganglion neurones of bullfrog SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RAT SYMPATHETIC NEURONS; SENSORY NEURONS; MAMMALIAN NEURONS; SYNAPTIC TRANSMISSION; CULTURED NEURONS; CHANNELS; RECEPTOR; PURINOCEPTORS; NODOSE; ANTAGONISTS AB 1. The effect of Zn2+ on ATP-activated current was studied in bullfrog dorsal root ganglion (DRG) neurones using the whole-cell patch-clamp technique. 2. Zn2+ (2-800 mu M) inhibited current activated by submaximal concentrations of ATP. The Zn2+ concentration that produced 50 % inhibition (IC50) of current activated by 2.5 mu M ATP was 61 +/- 9.8 mu M. When ATP concentrations were adjusted to account for chelation of Zn2+ the IC50 of Zn2+ was 86 +/- 18 mu M. 3. The inhibitory action of Zn2+ on ATP-gated channels did not appear to be due to a decrease in the concentration of one or more species of ATP. 4. Zn2+ inhibition of ATP-activated current was independent of membrane potential between -80 and +40 mV, and did not involve a shift in the reversal potential of the current. 5. Zn2+ (100 mu M) shifted the ATP concentration-response curve to the right in a parallel manner, increasing the EC50 for ATP from 2.5 +/- 0.5 mu M to 5.5 +/- 0.4 mu M. 6. Zn2+ decreased the time constant of deactivation of ATP-gated ion channels without affecting the time constant of activation or desensitization. 7. Dithiothreitol (DTT) reversed Zn2+ inhibition of ATP-activated current. 8. 2-Methylthio ATP, alpha,beta-methylene ATP and ADP activated current with EC50 values of 2.4 +/- 0.3, 50 +/- + 5.8 and 303.1 +/- 53.9 mu M, respectively. Adenosine, AMP or beta,gamma-methylene ATP did not evoke detectable current. 9. Reactive Blue 2 and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited ATP-activated current. 10. The results suggest that Zn2+ can inhibit P2X purinoceptor function by decreasing the affinity of the binding site for ATP. These observations provide the first evidence for this action of Zn2+ on a neurotransmitter-gated ion channel. Furthermore, the receptor-channel in these neurones appears to be a novel member of the P2X purinoceptor class. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Rockville, MD 20852 USA. RP Li, CY (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, 12501 Washington Ave, Rockville, MD 20852 USA. NR 40 TC 38 Z9 40 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 1997 VL 505 IS 3 BP 641 EP 653 DI 10.1111/j.1469-7793.1997.641ba.x PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP190 UT WOS:000071251600009 PM 9457642 ER PT J AU Song, LS Stern, MD Lakatta, EG Cheng, HP AF Song, LS Stern, MD Lakatta, EG Cheng, HP TI Partial depletion of sarcoplasmic reticulum calcium does not prevent calcium sparks in rat ventricular myocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CA2+ SPARKS; CARDIAC MYOCYTES; INDUCED RELEASE; HEART-MUSCLE; CONTRACTION; CELLS; CHANNEL; CALSEQUESTRIN; INACTIVATION; ACTIVATION AB 1. The exact nature of calcium sparks in the heart remains highly controversial. We sought to determine whether calcium sparks arise from a single or multiple calcium release channels/ryanodine receptors in the sarcoplasmic reticulum (SR). If their genesis involves a calcium-coupled recruitment of multiple channels, calcium sparks might be abolished by a modest depletion of SR calcium (because of the decrease in unitary calcium flux and hence a decrease in the gain of local calcium-induced calcium release). If, on the other extreme, calcium sparks are produced despite severe SR depletion, the single-channel origin will be preferred. 2. Spontaneous calcium sparks were studied in rat ventricular myocytes using confocal microscopy and the fluorescent calcium probe fluo-3. a computer algorithm was developed to count and measure objectively calcium sparks in linescan images. 3. Thapsigargin (25-150 nM) depleted caffeine-releasable SR calcium by up to 64%, in a dose- and time-dependent manner, without altering the resting cytosolic calcium level. During SR depletion, calcium sparks were robustly observed, albeit at reduced frequency (greater than or equal to 30% of control) and amplitude (greater than or equal to 60 % of control). 4. Due to the reduced detectability of small sparks against noise background, the observed data would overestimate reduction in spark frequency but underestimate amplitude reduction. After correction for this detection bias, we found that the spark frequency was independent of SR load, whereas the amplitude was proportional to load. 5. We conclude that, although spark amplitude depends on SR filling status, the frequency of spark generation is independent of SR calcium load, and therefore independent of the local calcium release rate. This implies that sparks are single-channel events, or collective events that are well above threshold for local regeneration. Additionally, our results suggest that intraluminal SR calcium, at normal or low loads, does not play a major role in the regulation of on-gating of the ryanodine receptor. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 29 TC 59 Z9 63 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 1997 VL 505 IS 3 BP 665 EP 675 DI 10.1111/j.1469-7793.1997.665ba.x PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP190 UT WOS:000071251600011 PM 9457644 ER PT J AU Wallace, WC Akar, CA Lyons, WE AF Wallace, WC Akar, CA Lyons, WE TI Amyloid precursor protein potentiates the neurotrophic activity of NGF SO MOLECULAR BRAIN RESEARCH LA English DT Article DE amyloid precursor protein; neurotrophic activity; nerve growth factor; growth factor potentiation ID NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; ALZHEIMERS-DISEASE; NUCLEUS BASALIS; SECRETED FORMS; CELL-SURFACE; RAT-BRAIN; PC12 CELLS; BETA; NEURONS AB Cortical amyloid precursor protein (APP) is induced and secreted in response to subcortical lesions of cholinergic innervation. To understand the physiological role of the induced APP, we have characterized its neurotrophic activity on PC12 cells. Highly purified human APP(751) (50-1000 pM) induced outgrowth of neurites. The neurotrophic activity was inhibited by an antibody that was directed to the C-terminal portion of the secreted APP but not by an antibody directed to the KPI domain. The neurotrophic activity of APP was independent of the TrkA NGF receptor because neither phospholipase C-gamma(1) nor TrkA exhibited tyrosine phosphorylations with APP treatment. Furthermore, APP stimulated neurite outgrowth from PC12 cells lacking TrkA receptors. At lower concentrations (10-50 pM), APP synergistically potentiated the neurotrophic effects of NGF when added with NGF or before NGF as a priming pretreatment. These results implicate APP, a rapidly induced protein in the injured cortex, as a potentiating agent that may render compromised neurons more responsive to low levels of NGF or other neurotrophins. (C) 1997 Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Mol & Cellular Biol Lab, Baltimore, MD 21224 USA. RP Wallace, WC (reprint author), NIA, Gerontol Res Ctr, Mol & Cellular Biol Lab, 4940 Eastern Ave,Bayview Campus, Baltimore, MD 21224 USA. NR 36 TC 35 Z9 36 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 DEC 15 PY 1997 VL 52 IS 2 BP 201 EP 212 DI 10.1016/S0169-328X(97)00258-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YU567 UT WOS:000071730800004 ER PT J AU Wallace, WC Akar, CA Lyons, WE Kole, HK Egan, JM Wolozin, B AF Wallace, WC Akar, CA Lyons, WE Kole, HK Egan, JM Wolozin, B TI Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity SO MOLECULAR BRAIN RESEARCH LA English DT Article DE amyloid precursor protein; neurotrophic activity; nerve growth factor; insulin receptor substrate-1; tyrosine phosphorylation; growth factor potentiation ID NERVE GROWTH-FACTOR; ISCHEMIC BRAIN INJURY; NEURO-BLASTOMA CELLS; FACTOR-I; SECRETED FORMS; BINDING-SITES; PC12 CELLS; RAT-BRAIN; PHOSPHATIDYLINOSITOL 3-KINASE; GLIAL-CELLS AB Picomolar concentrations of purified amyloid precursor protein (APP) potentiate the neurotrophic activity of suboptimal concentrations of NGF on PC12 cells. To understand the molecular basis for this potentiation, we have characterized the signal transduction pathway used by APP for its neurotrophic activity, APP stimulated the tyrosine phosphorylation of a number of proteins including insulin receptor levels and inhibition of APP stimulated neurite outgrowth. Phosphotidylinositol 3-kinase became associated with IRS-1 and activated upon APP stimulation. Extracellular signal-regulated kinase (ERK 1 and ERK 2) phosphorylation was detected by both immunoblot analysis and immunocytochemistry using antibodies directed to their phosphorylated (and hence, activated) form. There was also an elevation of ERK kinase activity. The potentiation of NGF activity was reflected in a correspondingly synergistic elevation of tyrosine phosphorylated ERK. The pattern of signal transduction targets indicates that APP potentiated the neurotrophic effects of NGF via the activation of the IRS-1 signaling pathway. (C) 1997 Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Clin Physiol Lab, Baltimore, MD 21224 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Wallace, WC (reprint author), NIA, Gerontol Res Ctr, Cellular & Mol Biol Lab, 4940 Eastern Ave,Johns Hopkins Bayview Campus, Baltimore, MD 21224 USA. NR 42 TC 28 Z9 37 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 DEC 15 PY 1997 VL 52 IS 2 BP 213 EP 227 DI 10.1016/S0169-328X(97)00259-3 PG 15 WC Neurosciences SC Neurosciences & Neurology GA YU567 UT WOS:000071730800005 ER PT J AU Hengen, PN Bartram, SL Stewart, LE Schneider, TD AF Hengen, PN Bartram, SL Stewart, LE Schneider, TD TI Information analysis of Fis binding sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI FIS; INVERSION STIMULATION FIS; RIBOSOMAL-RNA OPERONS; RRNB P1 PROMOTER; DNA INVERSION; RECOMBINATIONAL ENHANCER; PROTEIN FIS; UPSTREAM ACTIVATION; GEL-ELECTROPHORESIS; MOLECULAR MACHINES AB Originally discovered in the bacteriophage Mu DNA inversion system gin, Fis (Factor for Inversion Stimulation) regulates many genetic systems, To determine the base frequency conservation required for Fis to locate its binding sites, we collected a set of 60 experimentally defined wild-type Fis DNA binding sequences, The sequence logo for Fis binding sites showed the significance and likely kinds of base contacts, and these are consistent with available experimental data, Scanning with an information theory based weight matrix within fis, nrd, tgt/sec and gin revealed Fis sites not previously identified, but for which there are published footprinting and biochemical data, DNA mobility shift experiments showed that a site predicted to be 11 bases from the proximal Salmonella typhimurium hin site and a site predicted to be 7 bases from the proximal P1 cin site are bound by Fis in vitro. Two predicted sites separated by 11 bp found within the nrd promoter region, and one in the tgt/sec promoter, were also confirmed by gel shift analysis, A sequence in aldB previously reported to be a Fis site, for which information theory predicts no site, did not shift, These results demonstrate that information analysis is useful for predicting Fis DNA binding. C1 NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Frederick, MD 21702 USA. Middletown High Sch, Middletown, MD 21769 USA. RP Schneider, TD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, POB B,Bldg 469,Room 144, Frederick, MD 21702 USA. EM toms@nciferf.gov OI Schneider, Thomas/0000-0002-9841-1531 NR 84 TC 77 Z9 77 U1 0 U2 1 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 DEC 15 PY 1997 VL 25 IS 24 BP 4994 EP 5002 DI 10.1093/nar/25.24.4994 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YR469 UT WOS:000071498400020 PM 9396807 ER PT J AU Chen, TT AF Chen, TT TI Optimal three-stage designs for phase II cancer clinical tribes SO STATISTICS IN MEDICINE LA English DT Article ID MULTIPLE TESTING PROCEDURE; TRIALS; PROBABILITY; GUIDELINES; DRUG AB The objective of a phase II cancer clinical trial is to screen a treatment that can produce a similar or better response rate compared to the current treatment results. This screening is usually carried out in two stages as proposed by Simon. For ineffective treatment, the trial should terminate at the first stage. Ensign et al. extended two-stage optimal designs to three stages; however, they restricted the rejection region in the first stage to be zero response, and the sample size to at least 5. This paper extends Simon's two-stage to a three-stage design without these restrictions, and provides tables for both optimal and minimax designs. One can use the three-stage design to reduce the expected sample size when the treatment is not promising a priori and when the accrual rate is slow. The average reduction in size from a two-stage to three-stage design is 10 per cent. (C) 1997 by John Wiley & Sons, Ltd. RP Chen, TT (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 17 TC 79 Z9 80 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 1997 VL 16 IS 23 BP 2701 EP 2711 DI 10.1002/(SICI)1097-0258(19971215)16:23<2701::AID-SIM704>3.0.CO;2-1 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA YG633 UT WOS:A1997YG63300005 PM 9421870 ER PT J AU Troendle, JF Blair, RC Rumsey, D Moke, P AF Troendle, JF Blair, RC Rumsey, D Moke, P TI Parametric and non-parametric tests for the overall comparison of several treatments to a control when treatment is expected to increase variability SO STATISTICS IN MEDICINE LA English DT Article ID RESPOND; ANOVA AB We consider the problem of making an overall comparison of several treatments to a control where experimental units are randomly assigned to either the 'control' group which receives no treatment or to one of k - 1 'treatment' groups. We assume that the effect of the treatments is, if anything, a location shift possibly accompanied by an increase in scale relative to that of the control group. The ANOVA F test loses considerable power in such circumstances. A modification of the ANOVA F test has been proposed which uses the variance estimate from the controls in place of the usual pooled variance estimate. However, this modification has shortcomings when k exceeds two and the variances of the treatment groups are not inflated. We develop a combination procedure to avoid the pitfalls of the modified and usual F tests. We then propose parametric and non-parametric implementations of a likelihood ratio test that more efficiently incorporates the assumptions of this problem, yielding a test with a high power profile over a large range of normal alternatives. We use simulations to compare the power of the competing tests against several alternatives for normal and non-normal data. (C) 1997 by John Wiley & Sons, Ltd. C1 UNIV S FLORIDA,COLL PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,TAMPA,FL 33620. UNIV S FLORIDA,COLL PUBL HLTH,DEPT COMMUNITY & FAMILY HLTH,TAMPA,FL 33620. KANSAS STATE UNIV,DEPT STAT,MANHATTAN,KS 66506. RP Troendle, JF (reprint author), NICHHD,BIOMETRY BRANCH,DESPR,BLD 6100,RM 7B13,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY09435-01] NR 10 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 1997 VL 16 IS 23 BP 2729 EP 2739 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA YG633 UT WOS:A1997YG63300007 PM 9421872 ER PT J AU Dimitrov, DS AF Dimitrov, DS TI How do viruses enter cells? The HIV coreceptors teach us a lesson of complexity SO CELL LA English DT Editorial Material ID INFLUENZA HEMAGGLUTININ; ENVELOPE GLYCOPROTEIN; HUMAN RHINOVIRUS-14; MEMBRANE-FUSION; RECEPTOR; INFECTION; RESOLUTION; DOMAIN; COFACTOR; ANTIBODY RP Dimitrov, DS (reprint author), NCI,LAB EXPT & COMPUTAT BIOL,DBS,FCRDC,BLDG 469,ROOM 216,MILLER DR,FREDERICK,MD 21702, USA. NR 52 TC 96 Z9 97 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 12 PY 1997 VL 91 IS 6 BP 721 EP 730 DI 10.1016/S0092-8674(00)80460-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YL439 UT WOS:A1997YL43900003 PM 9413981 ER PT J AU Shakarian, AM Ellis, SL Mallinson, DJ Olafson, RW Dwyer, DM AF Shakarian, AM Ellis, SL Mallinson, DJ Olafson, RW Dwyer, DM TI Two tandemly arrayed genes encode the (histidine) secretory acid phosphatases of Leishmania donavani (vol 196, pg 127, 1997) SO GENE LA English DT Correction C1 NIAID, Cell Biol Sect, Lab Parasit Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA. Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 2Y2, Canada. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Lab Parasit Dis, Div Intramural Res,NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 1997 VL 203 IS 2 BP 251 EP 251 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YM161 UT WOS:000071035900020 ER PT J AU Katagiri, Y Hirata, Y Milbrandt, J Guroff, G AF Katagiri, Y Hirata, Y Milbrandt, J Guroff, G TI Differential regulation of the transcriptional activity of the orphan nuclear receptor NGFI-B by membrane depolarization and nerve growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING DOMAIN; INDUCIBLE MEMBER; GENE; PHOSPHORYLATION; SUPERFAMILY; ACTIVATION; EXPRESSION; KINASE; NUR77; PROTEIN AB The immediate-early gene NGFI-B (also called nur77) encodes an orphan nuclear receptor that activates transcription through a unique response element (NBRE), NGFI-B is rapidly induced and modified via phosphorylation by a variety of stimuli that induce cells to differentiate or to proliferate, We have shown that the in vitro phosphorylation of Ser(350) located within the ''A-box,'' a motif necessary for DNA binding by NGFI-B, results in a decrease in the binding of NGFI-B to its response element (Hirata, Y., Kiuchi, K., Chen, H.-C., Milbrandt, J., and Guroff, G, (1993) J, Biol. Chem. 268, 24808-24812). We show here that nerve growth factor (NGF)-induced changes in the in vivo phosphorylation of Ser(350) accompany transcriptional deactivation of NGFI-B in PC12 cells, that membrane depolarization and NGF treatment cause differential phosphorylation of NGFI-B, and that the transcriptional activation caused by exogenous expression of NGFI-B or membrane depolarization can be inhibited by NGF treatment, In addition, the mutation of Ser(350) to Ala abolished the inhibitory effect of NGF on the transcriptional activation of NGFI-B in PC12 cells, These data could provide new insights into the regulation of transcriptional activity required for some neurons to switch from activity-dependent survival to neurotrophin-dependent survival during development. C1 NICHHD,NIH,GROWTH FACTORS SECT,BETHESDA,MD 20892. RIKEN,BIOMIMET CONTROL RES CTR,MORIYAMA KU,NAGOYA,AICHI 463,JAPAN. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. NR 25 TC 67 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 1997 VL 272 IS 50 BP 31278 EP 31284 DI 10.1074/jbc.272.50.31278 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL419 UT WOS:A1997YL41900013 PM 9395454 ER PT J AU Shao, RG Cao, CX Pommier, Y AF Shao, RG Cao, CX Pommier, Y TI Activation of PKC alpha downstream from caspases during apoptosis induced by 7-hydroxystaurosporine or the topoisomerase inhibitors, camptothecin and etoposide, in human myeloid leukemia HL60 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; DNA FRAGMENTATION; HL-60 CELLS; THYMOCYTE APOPTOSIS; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY; ICE-LIKE; IN-VIVO; INDUCTION; UCN-01 AB We previously demonstrated that the anticancer agent and protein kinase C (PKC) inhibitor 7-hydroxy-staurosporine (UCN-01) induces apoptosis independently of p53 and protein synthesis in HL60 cells, We now report the associated changes of PKC isoforms, PKC alpha, beta I, beta II, delta, and zeta activities were measured after immunoprecipitation of cytosols from UCN-01-treated HL60 cells. UCN-01 had no effect on PKC zeta and inhibited kinase activity of PKC beta I, beta II, and delta. PKC alpha activity was initially inhibited at 1 h, and subsequently increased as cells underwent apoptosis 3 h after the beginning of UCN-01 treatment, Camptothecin (CPT) and etoposide (VP-16) also markedly enhanced PKC alpha activity during apoptosis in HL60 cells. However, CPT did not affect PKC beta I, beta II and zeta, and activated PKC delta, PKC alpha activation was not due to increased protein levels or proteolytic cleavage but was associated with PKC alpha autophosphorylation in vitro and increased phosphorylation in vivo, We also found that not only PKC delta but also PKC beta I was proteolytically activated in HL60 cells during apoptosis. The PKC alpha activation and hyperphosphorylation were abrogated by N-benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoro-methylketone (z-VAD-fmk) under conditions that abrogated apoptosis, z-VAD-fmk also prevented PKC delta and beta I proteolytic activation, Together these findings suggest that caspases regulate PKC activity during apoptosis in HL60 cells, At least two modes of activation were observed: hyperphosphorylation for PKC alpha and proteolytic activation for PKC delta and beta I. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 36 TC 63 Z9 68 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 DEC 12 PY 1997 VL 272 IS 50 BP 31321 EP 31325 DI 10.1074/jbc.272.50.31321 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL419 UT WOS:A1997YL41900019 PM 9395460 ER PT J AU Ray, K Fan, GF Goldsmith, PK Spiegel, AM AF Ray, K Fan, GF Goldsmith, PK Spiegel, AM TI The carboxyl terminus of the human calcium receptor - Requirements for cell-surface expression and signal transduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSING RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MUTATIONS; RAT; PROTEINS AB The G-protein-coupled calcium receptor plays a key role in extracellular calcium homeostasis. To examine the role of the membrane-spanning domains and the similar to 200-residue cytoplasmic carboxyl terminus of the calcium receptor-in cell-surface expression and signal transduction, we transfected HEK-293 cells with a series of truncation and carboxyl-terminal missense mutants and analyzed expression by immunoblotting, glycosidase digestion, intact cell immunoassay, and extracellular calcium-stimulated phosphoinositide hydrolysis assay. Two truncation mutants terminating at residues 706 and 802 within the second and third intracellular loops, respectively, were not properly glycosylated, failed to reach the cell-surface, and showed no calcium response, indicating that mutant receptors with the full extracellular domain but only three or five transmembrane domains are improperly folded and/or processed. Truncation mutants terminating at residues 888 and 903 within the carboxyl terminus were equivalent to the wild type in all assays, whereas mutants truncated at residues 865 and 874 showed no response to calcium, despite only similar to 25% reduction in cell-surface expression. Mutants with a full-length carboxyl terminus but with residues between positions 874 and 888 replaced with alanines showed either no (Ala(875), Ala(876), and Ala(879)) or significantly reduced (Ala(881)-Ala(883)) calcium response at levels of cell-surface expression equivalent to those of the wild-type receptor. These results indicate that deletion of the majority of the carboxyl terminus is compatible with normal processing, cell-surface expression, and signal transduction of the receptor. The truncation and alanine substitution mutants identify a small region between residues 874 and 888 critical for normal signal transduction by the receptor. C1 NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 22 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 DEC 12 PY 1997 VL 272 IS 50 BP 31355 EP 31361 DI 10.1074/jbc.272.50.31355 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL419 UT WOS:A1997YL41900024 PM 9395465 ER PT J AU Zhang, WY Gaynor, PM Kruth, HS AF Zhang, WY Gaynor, PM Kruth, HS TI Aggregated low density lipoprotein induces and enters surface-connected compartments of human monocyte-macrophages - Uptake occurs independently of the low density lipoprotein receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE PERITONEAL-MACROPHAGES; FOAM-CELL-FORMATION; CULTURED-CELLS; CHOLESTEROL; LDL; PHAGOCYTOSIS; METABOLISM; OXIDATION; MECHANISM; DEGRADATION AB Aggregation of low density lipoprotein (LDL) stimulates its uptake by macrophages. We have now shown by electron microscopic and chemical experiments that aggregated LDL (produced by vortexing (VxLDL) or treatment with phospholipase C) induced and became sequestered in large amounts within surface-connected compartments (SCC) of human monocyte-derived macrophages. This occurred through a process different from phagocytosis, Formation of SCC and accumulation of aggregated LDL in SCC are cell-mediated processes that were temperature-dependent (10 x greater cell as association at 37 degrees C than at 4 degrees C) and blocked by cytochalasin D but not by nocodazole, Because of the surface connections of SCC, trypsin could release aggregated EDL from SCC, Degradation of I-125-VxLDL through the SCC pathway showed delayed and a lower rate of degradation (10-55%) compared with nonaggregated I-125-acetylated LDL that did not enter SCC. However, similar to I-125-acetylated LDL degradation, I-125-VxLDL degradation occurred through a chloroquine-sensitive pathway. Uptake of VxLDL into SCC was not mediated by the LDL receptor, Methylation of LDL prevents its binding to the LDL receptor, However, methylated LDL still entered SCC after it was aggregated by vortexing, On the other hand, degradation of I-125-VxLDL was substantially decreased by methylation of LDL and by cholesterol enrichment of macrophages, which decreases macrophage LDL receptor expression, The results suggest that whereas uptake of aggregated LDL into SCC occurs independently of the LDL receptor, movement of aggregated LDL from SCC to lysosomes may depend in part on LDL receptor function. Sequestration into SCC is a novel endocytosis pathway for uptake of aggregated LDL that allows the macrophage to store large amounts of this lipoprotein before it is further processed. C1 NHLBI,SECT EXPT ATHEROSCLEROSIS,NIH,BETHESDA,MD 20892. NR 34 TC 50 Z9 50 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 DEC 12 PY 1997 VL 272 IS 50 BP 31700 EP 31706 DI 10.1074/jbc.272.50.31700 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL419 UT WOS:A1997YL41900071 PM 9395512 ER PT J AU Chiron, MF Fryling, CM FitzGerald, D AF Chiron, MF Fryling, CM FitzGerald, D TI Furin-mediated cleavage of Pseudomonas exotoxin-derived chimeric toxins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; RECEPTOR-RELATED PROTEIN; DIPHTHERIA-TOXIN; CYTOPLASMIC DOMAIN; CELL-SURFACE; MOUSE FURIN; ACTIVATION; LOCALIZATION; EXPRESSION; SEQUENCE AB Pseudomonas exotoxin (PE) requires proteolytic cleavage to generate a 37-kDa C-terminal fragment that translocates to the cytosol and ADP-ribosylates elongation factor 2. Cleavage within cells is mediated by furin, occurs between arginine 279 and glycine 280, and requires an arginine at both P1 and P4 residues. To study the proteolytic processing of PE-derived chimeric toxins, TGF alpha-PE38 (transforming growth factor fused to the domains II and III of PE) and a mutant form, TGF alpha-PE38gly279, were each produced in Escherichia coli, When assessed on various epidermal growth factor (EGF) receptor-positive cell lines, TGF alpha-PE38 was 100-500-fold more toxic than TGF alpha-PE38gly279. In contrast to PE, where cleavage by furin is only evident at pH 5.5, furin cleaved TGF alpha-PE38 over a broad pH range, while TGF alpha-PE38gly279 was resistant to cleavage, TGF alpha-PE38 was poorly toxic for furin-deficient LoVo cells, unless it was first pretreated in vitro with furin, Furin treatment produced a nicked protein that was 30-fold more toxic than its unnicked counterpart. Using the single chain immunotoxin HB21scFv-PE40 as a substrate, furin-mediated processing of an antibody-based immunotoxin was also evaluated, HB21scFv-PE40, which targets cells expressing the transferrin receptor, was cleaved in a similar fashion to that of TGF alpha-PE38 and nicked HB21scFv-PE40 exhibited increased toxicity for LoVo cells, In short-term experiments, the rate of reduction in protein synthesis by furin-nicked immunotoxins was increased compared with unnicked protein, indicating that cleavage by furin can be a rate-limiting step, We conclude that furin-mediated cleavage of PE-derived immunotoxins is important for their cytotoxic activity. C1 NCI,BIOTHERAPY SECT,MOL BIOL LAB,DBS,NIH,BETHESDA,MD 20892. NR 34 TC 29 Z9 29 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 DEC 12 PY 1997 VL 272 IS 50 BP 31707 EP 31711 DI 10.1074/jbc.272.50.31707 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL419 UT WOS:A1997YL41900072 PM 9395513 ER PT J AU Oka, H Iwaya, M Harada, K Murata, H Suzuki, M Ikai, Y Hayakawa, J Ito, Y AF Oka, H Iwaya, M Harada, K Murata, H Suzuki, M Ikai, Y Hayakawa, J Ito, Y TI Effect of foaming power and foam stability on continuous concentration with foam counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; foaming power; foam stability; gardenia yellow; bacitracin; peptides; dyes; triterpenoids; saponins; xanthenes; microcystins AB In order to facilitate the application of the foam counter-current chromatography (CCC) technique to various natural products, we have introduced two parameters, i.e., "foaming power" and "foam stability", which reliably indicate applicability of the sample to foam CCC. In each test, the sample was delivered into a graduated cylinder with a ground stopper followed by vigorous shaking. The foaming power was expressed by the volume ratio of the resulting foam to the remaining solution, and the foam stability by the duration of the foam. A set of data obtained from various samples including bacitracin, gardenia yellow, phloxine B, rose bengale and senega methanol extract revealed a significant correlation between these parameters and the degree of foam enrichment by foam CCC. The overall results indicated that a sample with the following properties may be effectively enriched by foam CCC: the foaming power is greater than 1.0 and the foam stability is over 250 min. We applied these experimental results to the enrichment of microcystins in a cyanobacteria bloom sample extract using foam CCC. (C) 1997 Elsevier Science B.V. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 462, Japan. Meijo Univ, Fac Pharm, Tempa Ku, Nagoya, Aichi 468, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 462, Japan. NR 4 TC 6 Z9 7 U1 3 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 DEC 12 PY 1997 VL 791 IS 1-2 BP 53 EP 63 DI 10.1016/S0021-9673(97)00825-X PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YT285 UT WOS:000071584800005 ER PT J AU Postnikov, YV Herrera, JE Hock, R Scheer, U Bustin, M AF Postnikov, YV Herrera, JE Hock, R Scheer, U Bustin, M TI Clusters of nucleosomes containing chromosomal protein HMG-17 in chromatin SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE chromatin; nucleosome; high mobility group proteins; immunoprecipitation; immunofluorescence ID HIGHER-ORDER STRUCTURE; MOBILITY GROUP PROTEIN-14; TRANSCRIPTION INITIATION; ARCHITECTURAL ELEMENTS; BINDING DOMAIN; MODULATION; CORES; CONFORMATION; ORIENTATION; ELONGATION AB Chromosomal proteins HMG-14 and HMG-17 are nucleosome binding proteins which can function as architectural elements to alter the structure of the chromatin fiber and enhance transcription from chromatin templates. Here we study the spatial organization of these HMG proteins in the nucleus and the distribution of nucleosomes containing HMG-17 in the chromatin fiber. By confocal immunofluorescence microscopy we find tl-rat HMG-14/17 proteins are clustered into foci containing either HMG-14 or HMG-17. These results suggest that HMG-14/17 proteins segregate into distinct nuclear domains. Indeed, immunofractionation of defined length oligonucleosomes, with affinity pure antibodies to HMG-17, indicates that oligonucleosomes containing HMG-17 are devoid of HMG-14. Quantitative analysis indicates that in cellular chromatin nucleosomes containing HMG-17 are clustered. The average size of the cluster is six contiguous HMG-17-containing nucleosomes. The nucleosomes in this cluster contain either two or zero molecules of HMG-17 and a complete set of four core histones. We suggest that HMG-14/17 proteins modify the nucleosomal organization of the 30 nm chromatin fiber, to unfold the higher order chromatin structure and facilitate access to the underlying DNA sequence. Clustering of architectural elements, such as HMG proteins and linker histone subtypes into distinct domains, may lead to structural and functional heterogeneity along the chromatin fiber. (C) 1997 Academic Press Limited. C1 NCI, Prot Sect, LMC, DBS,NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Cell & Dev Biol, D-8700 Wurzburg, Germany. RP Bustin, M (reprint author), NCI, Prot Sect, LMC, DBS,NIH, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 55 TC 46 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 12 PY 1997 VL 274 IS 4 BP 454 EP 465 DI 10.1006/jmbi.1997.1391 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP198 UT WOS:000071252400003 PM 9417927 ER PT J AU Schmidt, BF Snyder, EJ Carroll, RM Farnsworth, DW Michejda, CJ Smith, RH AF Schmidt, BF Snyder, EJ Carroll, RM Farnsworth, DW Michejda, CJ Smith, RH TI Triazinines: Synthesis and proteolytic decomposition of a new class of cyclic triazenes SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID 1,3-DIALKYLTRIAZENES; TRIALKYLTRIAZENES; IMIDAZOTETRAZINES AB The reaction of 1-azido-3-chloropropane with various Grignard reagents and subsequent treatment with anhydrous isopropylamine results in the formation of the corresponding azimine. If the initial magnesium-triazene complex is first hydrolyzed with Dowex resin and then concentrated, the resultant linear triazene begins self-catalyzed cyclization to form the six-membered-ring triazenes as the major product, with HCl as the byproduct. Addition of an amine, at reduced temperature, allows for the neutralization of the byproduct, HCl, which would otherwise react with the linear triazene and the cyclic six-membered-ring triazene to form hydrolysis products. We have assigned the trivial name of triazinines to this new class of cyclic triazenes. The hydrolytic decomposition of these compounds in mixed acetonitrile-aqueous buffers predominantly forms 3-(alkylamino)-1-propanol and lesser amounts of the rearranged alcohol 1-(alkylamino)-2-propanol and N-alkyl-2-propenamine. The rate of hydrolysis of 1-alkyltriazinines is approximately equal to that of the analogous 1,3,3-trialkyltriazenes, about three times slower than that of the analogous 1-alkyltriazolines, and varies in the order ethyl > butyl > 3,3-diethoxypropyl > benzyl, As was true for other triazenes, the mechanism of the decomposition was found to be specific acid-catalyzed (Al), involving rapid reversible protonation followed by rate-limiting formation of a 3-(alkylamino)propyldiazonium ion. The slopes of the log k(obs) versus pH plots were near -1.0. The solvent deuterium isotope effect, k(H2O)/k(D2O), was in all cases <1.0 and ranges from 0.82 for 1-benzyltriazinine to 0.89 for 1-ethyltriazinine. The activation parameters of the proteolytic decomposition of a series, 1-ethyltriazinine, 1-ethyltriazoline, 1,3,3-triethyltriazene, and 1-ethyl-3-methyltriazene, had similar values for Delta H-double dagger (+9 --> 12 kcal/mol) and Delta S-double dagger (+7 --> 15 eu), respectively. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. NR 21 TC 8 Z9 8 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 12 PY 1997 VL 62 IS 25 BP 8660 EP 8665 DI 10.1021/jo970721p PG 6 WC Chemistry, Organic SC Chemistry GA YL206 UT WOS:A1997YL20600016 ER PT J AU Bishop, JB Witt, KL Sloane, RA AF Bishop, JB Witt, KL Sloane, RA TI Genetic toxicities of human teratogens SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review ID SISTER-CHROMATID EXCHANGES; NATIONAL-TOXICOLOGY-PROGRAM; HAMSTER OVARY CELLS; MOUSE LYMPHOMA CELL; POLYCYCLIC AROMATIC-HYDROCARBONS; DOMINANT-LETHAL MUTATIONS; SALMONELLA-MICROSOME TEST; TUMOR-NECROSIS-FACTOR; BONE-MARROW CELLS; GROWTH-FACTOR-I AB Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family, Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase, Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-10% to exposure to a known teratogenic agent or maternal factor [D.A. Beckman, R.L, Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol, 24 (1984) 483-500; K. Nelson, L.B. Holmes, Malformations due to presumed spontaneous mutations in newborn infants, N. Engl. J. Med. 320 (1989) 19-23.]. Together, these percentages account for only 30-40%, leaving the etiology of more than half of all human birth defects unexplained. It has been speculated that environmental factors account for no more than one-tenth of all congenital anomalies [D.A. Beekman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 383-500], Furthermore, since 'there is no evidence in humans that the exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring' [J.F. Crow, C. Denniston, Mutation in human populations, Adv. Human Genet. 14 (1985) 59121; J.M. Friedman, J.E. Polifka, Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS), The John Hopkins University Press, Baltimore, 1994], the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention, Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular methods are developed for assessing processes associated with teratogenesis, especially those with a genetic or an epigenetic basis, additional environmental factors may be identified. These are especially important because they are potentially preventable. This paper examines the relationships between chemicals identified as human teratogens (agents that cause birth defects) and their mutagenic activity as evaluated in one or more of the established short-term bioassays currently used to measure such damage. Those agents lacking mutagenic activity but with published evidence that they may otherwise alter the expressions or regulate interactions of the genetic material, i.e. exhibit epigenetic activity, have likewise been identified. The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Toxicology Program (NTP). (C) 1997 Elsevier Science B.V. C1 NIEHS, Toxicol Lab, Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. Oak Ridge Inst Sci Educ, Oak Ridge, TN USA. RP Bishop, JB (reprint author), NIEHS, Toxicol Lab, Reprod Toxicol Grp, POB 12233 A2-10, Res Triangle Pk, NC 27709 USA. NR 301 TC 34 Z9 38 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 12 PY 1997 VL 396 IS 1-2 SI SI BP 9 EP 43 DI 10.1016/S0027-5107(97)00173-5 PG 35 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YN777 UT WOS:000071205500002 PM 9434858 ER PT J AU Studitsky, VM Kassavetis, GA Geiduschek, EP Felsenfeld, G AF Studitsky, VM Kassavetis, GA Geiduschek, EP Felsenfeld, G TI Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase SO SCIENCE LA English DT Article ID CHAIN ELONGATION; INITIATION; TEMPLATES; DNA; CHROMATIN; COMPLEXES; INVITRO AB Nucleosomes, the nucleohistone subunits of chromatin, are present on transcribed eukaryotic genes but do not prevent transcription. It is shown here that the large yeast RNA polymerase III transcribes through a single nucleosome. This takes place through a direct internal nucleosome transfer in which histones never leave the DNA template, During this process, the polymerase pauses with a pronounced periodicity of 10 to 11 base pairs, which is consistent with restricted rotation in the DNA loop formed during transfer. Transcription through nucleosomes by the eukaryotic enzyme and by much smaller prokaryotic RNA polymerases thus shares many features, reflecting an important property of nucleosomes. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR MOL GENET,LA JOLLA,CA 92093. RI Studitsky, Vasily/A-9382-2014 NR 25 TC 144 Z9 145 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 12 PY 1997 VL 278 IS 5345 BP 1960 EP 1963 DI 10.1126/science.278.5345.1960 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YL002 UT WOS:A1997YL00200039 PM 9395401 ER PT J AU Wang, XT Gorospe, M Huang, Y Holbrook, NJ AF Wang, XT Gorospe, M Huang, Y Holbrook, NJ TI p27(Kip1) overexpression causes apoptotic death of mammalian cells SO ONCOGENE LA English DT Article DE apoptosis; cdk inhibitor; cell growth; Bcl-2 ID DEPENDENT KINASE INHIBITOR; ANTICANCER AGENTS; CARCINOMA CELLS; CDK INHIBITORS; MICE LACKING; CYCLE ARREST; G(1) ARREST; GROWTH; P21; DIFFERENTIATION AB p27(Kip1), a member of the Cip/Kip family of cyclin-dependent kinase (cdk) inhibitors, has been Implicated in mediating G1 arrest in response to a variety of growth inhibitory signals, Its importance in regulating cell growth is emphasized by the fact that mice lacking p27(Kip1) are abnormally large and display hyperplasia of multiple tissues, However, these mice retain the ability to undergo G1 arrest in response to growth inhibitory signals, suggesting that p27(Kip1) may serve other functions important for controlling tissue growth, In the present study, we utilized an adenoviral vector-based expression system to examine the consequences of p27(Kip1) overexpression in the human carcinoma cell lines A549, HeLa and RKO, in human melanoma SK-MEL-110 cells, in human lung fibroblasts IMR90 and in the rat fibroblast line Rat1, We demonstrate that overexpression of p27(Kip1) leads to apoptotic cell death in all cell types, and further show that ectopic expression of Bcl-2 can protect HeLa cells from apoptosis mediated by p27(Kip1) overexpression, To our knowledge, this is the first study demonstrating that p27(Kip1) can induce apoptosis, Our findings provide new insight into the possible functions of this growth regulatory protein, and support the potential utility of gene therapeutic approaches aimed at elevating p27(Kip1) expression for treatment of human cancers. C1 NIA,GENE EXPRESS & AGING SECT,BIOL CHEM LAB,NIH,BALTIMORE,MD 21224. NR 31 TC 171 Z9 185 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 11 PY 1997 VL 15 IS 24 BP 2991 EP 2997 DI 10.1038/sj.onc.1201450 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YK377 UT WOS:A1997YK37700012 PM 9416843 ER PT J AU Galetsky, SA Tsvetnov, VV Land, CE Afanasieva, TA Petrovichev, NN Gurtsevitch, VE Tokunaga, M AF Galetsky, SA Tsvetnov, VV Land, CE Afanasieva, TA Petrovichev, NN Gurtsevitch, VE Tokunaga, M TI Epstein-Barr-virus-associated gastric cancer in Russia SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CARCINOMA; EXPRESSION; INFECTION; CELLS AB The present investigation was carried out to estimate the prevalence of EBV-associated cases among gastric carcinoma (GC) patients of Russia and the Republics of the former Soviet Union (FSU). With this aim, formalin-fixed paraffin-embedded blocks from 206 gastric carcinomas obtained from patients of the Cancer Research Center, Moscow, were investigated by EBV-encoded RNA-1 (EBER-1) in situ hybridization applied to paraffin sections. As a result, 18 GC cases (8.7%) revealed uniform EBER-1 expression restricted to the carcinoma cells. Hybridized signals not detected in nonneoplastic gastric epithelium. EBV involvement was significantly more frequent among males, especially in tumors of less differentiated types (moderately differentiated tubular adenocarcinomas and poorly differentiated solid adenocarcinomas) and located in the upper stomach (cardia and middle). Most EBV-positive GCs were characterized by strong lymphoid-compartment involvement. Our findings concerning the distribution of EBV-positive GCs by sex, site and hystological type ave similar to those in Japan, however, EBV-positive rate of GC cases in Russia is higher than in Japan and lower than in USA. (C) 1997 Wiley-Liss, Inc. C1 RUSSIAN ACAD MED SCI,CANC RES CTR,INST CARCINOGENESIS,MOSCOW 115478,RUSSIA. NCI,RADIAT EPIDEMIOL BRANCH,EPN 408,BETHESDA,MD 20892. KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. OI Gurtsevitch, V.E./0000-0003-1840-4364 NR 22 TC 40 Z9 43 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 DEC 10 PY 1997 VL 73 IS 6 BP 786 EP 789 PG 4 WC Oncology SC Oncology GA YJ834 UT WOS:A1997YJ83400002 PM 9399652 ER PT J AU Fleisher, TA Tomar, RH AF Fleisher, TA Tomar, RH TI Introduction to diagnostic laboratory immunology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LEUKOCYTES AB Assays performed in the diagnostic immunology laboratory support the diagnosis and management of a wide spectrum of clinical conditions. This chapter reviews immunologic principles as they apply to diagnostic laboratory assays. Most of the determinations are based on well-established principles of antigen-antibody reactions. Some of the specific areas discussed include flow cytometric analyses, critical in the care of patients with hematologic malignancies, with the acquired immunodeficiency syndrome, or undergoing transplantation, and protein electrophoretic assays to identify the presence of monoclonal gammopathies. We also discuss the use of molecular techniques in the diagnosis of hematologic malignancies and primary immunodeficiencies, characterization of the major histocompatibility complex, and enumeration of viral burden. C1 UNIV WISCONSIN HOSP & CLIN,DEPT PATHOL & LAB MED,CLIN SCI CTR E5483,MADISON,WI 53792. RP Fleisher, TA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,SERV IMMUNOL,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2C410,BETHESDA,MD 20892, USA. NR 62 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 1997 VL 278 IS 22 BP 1823 EP 1834 DI 10.1001/jama.278.22.1823 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA YK155 UT WOS:A1997YK15500004 PM 9396643 ER PT J AU Puck, JM AF Puck, JM TI Primary immunodeficiency diseases SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLASS-II DEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; X-LINKED AGAMMAGLOBULINEMIA; COMBINED IMMUNE-DEFICIENCY; WISKOTT-ALDRICH SYNDROME; HYPER-IGM SYNDROME; LYMPHOPROLIFERATIVE SYNDROME; TYROSINE KINASE; GENE; MUTATIONS AB Primary immunodeficiencies are rare, but important for 3 reasons. First, a high index of suspicion and prompt diagnosis can lead to lifesaving treatment or significant improvement in quality of life. Second, appreciation of the genetic nature of a host defense defect makes possible family counseling and carrier and prenatal diagnosis. Finally, the large and growing list of human genetic defects in immune pathways provides an important tool for understanding human immunoregulation. Many inherited immunodeficiency diseases have had their genetic cause proven with the discovery of their disease genes within the past 5 years. These diseases provide a framework into which additional diseases and disease gene discoveries can be added as the rapid progress in molecular immunology and genetics continues. RP Puck, JM (reprint author), NATL HUMAN GENOME RES INST,IMMUNOL DIS SECT,LAB GENE TRANSFER,NIH,BLDG 49,ROOM 3A14,BETHESDA,MD 20892, USA. NR 59 TC 19 Z9 20 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 1997 VL 278 IS 22 BP 1835 EP 1841 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YK155 UT WOS:A1997YK15500005 PM 9396644 ER PT J AU Liu, Y Ruoho, AE Rao, VD Hurley, JH AF Liu, Y Ruoho, AE Rao, VD Hurley, JH TI Catalytic mechanism of the adenylyl and guanylyl cyclases: Modeling and mutational analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STEREOCHEMICAL COURSE; PROTEIN STRUCTURES; MOLECULAR-CLONING; BOVINE LUNG; DOMAINS; ENZYME; PARAMETERS; REFINEMENT; FORSKOLIN; SEQUENCE AB The adenylyl and guanylyl cyclases catslyze the formation of 3 ',5 ' cyclic adenosine or guanosine monophosphate from the corresponding nucleoside 5 '-triphosphate. The guanylyl cyclases, the mammalian adenylyl cyclases, and their microbial homologues function as pairs of homologous catalytic domains. The crystal structure of the rat type II adenylyl cyclase C-2 catalytic domain was used to model by homology a mammalian adenylyl cyclase C-1-C-2 domain pair, a homodimeric soluble cyclase of dictyostelium discoideum, a heterodimeric soluble guanylyl cyclase, and a homodimeric membrane guanyly cyclase. Mg(2+)ATP or Mg(2+)GTP were docked into the active sites based on known stereochemical constraints on their conformation. The models are consistent with the activities of seven active-site mutants. Asp-310 and Glu-432 of type 1 adenylyl cyclase coordinate a Mg(2+)ion. The D310S and D310A mutants have lO-fold reduced V-max and altered [Mg2+] dependence. The NTP purine moieties bind in mostly hydrophobic pockets. Specificity is conferred by a Lys and an Asp in adenylyl cyclase, and a Glu, an Arg, and a Cys in guanyly cyclase. The models predict that an Asp from one domain is a general base in the reaction, and that the transition state is stabilized by a conserved Asn-Arg pair on the other domain. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. FU NIGMS NIH HHS [R01 GM033138, GM33138] NR 53 TC 187 Z9 196 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13414 EP 13419 DI 10.1073/pnas.94.25.13414 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500012 PM 9391039 ER PT J AU Johnen, G Kaufman, S AF Johnen, G Kaufman, S TI Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYDROXYLASE-STIMULATING PROTEIN; AMINO-ACID HYDROXYLASES; RNA-BINDING DOMAIN; PHENYLALANINE-HYDROXYLASE; 4A-CARBINOLAMINE DEHYDRATASE; CRYSTAL-STRUCTURE; 4A-HYDROXYTETRAHYDROPTERIN DEHYDRATASE; PTERIN-4A-CARBINOLAMINE DEHYDRATASE; HOMEODOMAIN PROTEINS; RAT-LIVER AB The relationship between the enzymatic and the transcriptional activity of the bifunctional protein pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear factor 1 (DCoH) has been elucidated by site-directed mutagenesis. DCoH dimers harbor a binding site for hepatocyte nuclear factor 1 (HNF1), two active centers that bind pterins, and a saddle-shaped surface that resembles nucleic acid binding domains. Two domains of the protein have been selectively targeted to determine if a change in one activity affects the other. No strong correlation has been found, supporting the idea that carbinolamine dehydratase activity is not required for HNF1 binding in vitro or transcriptional coactivation in vivo. Double mutations in the active center, however, influence the in vivo transcriptional activity but not HNF1 binding. This finding suggests that some active center residues also are used during transcription, possibly for binding of another (macro)molecule. Several mutations in the saddle led to a surprising increase in transcription, therefore linking this domain to transcriptional regulation as well. The transcriptional function of DCoH therefore is composed of two parts, HNF1 binding and another contributing effect that involves the active site and, indirectly, the saddle. C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NR 42 TC 20 Z9 20 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13469 EP 13474 DI 10.1073/pnas.94.25.13469 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500022 PM 9391049 ER PT J AU Seok, YJ Sun, JZ Kaback, HR Peterkofsky, A AF Seok, YJ Sun, JZ Kaback, HR Peterkofsky, A TI Topology of allosteric regulation of lactose permease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; SUBSTRATE-BINDING SITE; LAC CARRIER PROTEIN; ESCHERICHIA-COLI; ENZYME IIA; PHOSPHOENOLPYRUVATE; MUTAGENESIS; COMPONENT; COMPLEX; MUTANTS AB Sugar transport by some permeases in Escherichia coli is allosterically regulated by the phosphorylation state of the intracellular regulatory protein, enzyme IIA(glc) of the phosphoenolpyruvate:sugar phosphotransferase system. A sensitive radiochemical assay for the interaction of enzyme IIA(glc) with membrane-associated lactose permease was used to characterize the binding reaction. The binding is stimulated by transportable substrates such as lactose, melibiose, and raffinose, but not by sugars that are not transported (maltose and sucrose). Treatment of lactose permease with N-ethylmaleimide, which blocks ligand binding and transport by alkylating Cys-148, also blocks enzyme IIA(glc) binding. Preincubation with the substrate analog beta-D-galactopyranosyl 1-thio-beta-D-galactapyranoside protects both lactose transport and enzyme IIA(glc) binding against inhibition by ethylmaleimide. A collection of lactose permease replacement mutants at Cys-148 showed, with the exception of C148V, a good correlation of relative transport activity and enzyme IIA(glc) binding. The nature of the interaction of enzyme IIA(glc) with the cytoplasmic face of lactose permease was explored. The N- and C-termini, as well as five hydrophilic loops in the permease, are exposed on the cytoplasmic surface of the membrane and it has been proposed that the central cytoplasmic loop of lactose permease is the major determinant for interaction with enzyme IIA(glc). Lactose permease mutants with polyhistidine insertions in cytoplasmic loops IV/V and VI/VII and periplasmic loop VII/VIII retain transport activity and therefore substrate binding, but do not bind enzyme IIA(glc), indicating that these regions of lactose permease may be involved in recognition of enzyme IIA(glc). Taken together, these results suggest that interaction of lactose permease with substrate promotes a conformational change that brings several cytoplasmic loops into an arrangement optimal for interaction with the regulatory protein, enzyme IIA(glc). A topological map of the proposed interaction is presented. C1 NHLBI,LAB BIOCHEM GENET,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,DEPT PHYSIOL & MICROBIOL & MOL GENET,INST MOL BIOL,LOS ANGELES,CA 90024. NR 30 TC 20 Z9 20 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 DEC 9 PY 1997 VL 94 IS 25 BP 13515 EP 13519 DI 10.1073/pnas.94.25.13515 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500030 PM 9391057 ER PT J AU Kays, WT Piatigorsky, J AF Kays, WT Piatigorsky, J TI Aldehyde dehydrogenase class 3 expression: Identification of a cornea-preferred gene promoter in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR SOLUBLE-PROTEIN; BOVINE CORNEA; DEVELOPMENTAL REGULATION; ALCOHOL-DEHYDROGENASE; CRYSTALLIN GENE; BINDING PROTEIN; RAT; TRANSCRIPTION; SEQUENCE; ELEMENTS AB Aldehyde dehydrogenase class 3 (ALDH3) constitutes 20-40% of the total water-soluble proteins in the mammalian cornea. Here, we show by Northern blot analysis that ALDH3 expression in the mouse is al least 500-fold higher in the cornea than in any other tissue examined, with very love levels of expression detected in the stomach, urinary bladder, ocular lens, and lung. Histochemical localization reveals that this exceptional level of expression in the mouse cornea occurs in the anterior epithelial cells end that little ALDH3 Is present in the keratocytes or corneal endothelial cells. A 13-kbp mouse ALDH3 promoter fragment containing >22 kbp of the 5' flanking sequence, the 40-bp untranslated first exon, and 29 bp of intron 1 directed cat reporter gene expression to tissues that express the endogenous ALDH3 gene, except that transgene promoter activity was higher in the stomach and bladder than in the cornea. Bg contrast, when driven by a 4.4.kbp mouse ALDH3 promoter fragment [1,050-bp 5' flanking region, exon 1, intron 1 (3.4 kbp), and 7 bp or exon 2] expression of the cat reporter gene was confined to the corneal epithelial cells, except for very low levels in the liver, effectively reproducing the corneal expression pattern of the endogenous ALDH3 gene, These results indicate that tissue-specific expression of ALDH3 is determined by positive and negative elements in the 5' flanking region of the gene and suggests putative silencers located in intron 1. We demonstrate regulatory sequences capable of directing cornea-specific gene expression, affording the opportunity for genetic engineering in this transparent tissue. C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 50 TC 45 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13594 EP 13599 DI 10.1073/pnas.94.25.13594 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500044 PM 9391071 ER PT J AU SaintJeannet, JP He, X Varmus, HE Dawid, IB AF SaintJeannet, JP He, X Varmus, HE Dawid, IB TI Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID XENOPUS-LAEVIS EMBRYOS; PROTO-ONCOGENE INT-1; SPEMANN ORGANIZER; SONIC-HEDGEHOG; MOUSE EMBRYO; EXPRESSION; INDUCTION; NOGGIN; GENE; DIFFERENTIATION AB Members of the Wnt family of signaling molecules are expressed differentially along the dorsal-ventral axis of the developing neural tube. Thus me asked whether Wnt factors are involved in patterning of the nervous system along this axis. We show that Wnt-1 and Wnt-3a, both of which are expressed in the dorsal portion of the neural tube, could synergize with the neural inducers noggin and chordin in Xenopus animal explants to generate the most dorsal neural structure, the neural crest, as determined by the expression of Krox-20, AP-2, and slug. Overexpression of Wnt-1 or Wnt-3a in the neuroectoderm of whole embryos led to a dramatic increase of slug and Krox-20-expressing cells, but the hindbrain expression of Krox-20 remained unaffected. Enlargement in the neural crest population could occur even when cell proliferation was inhibited. Wnt-5A and Wnt-8, neither of which is expressed in the dorsal neuroectoderm, failed to induce neural crest markers. Overexpression of glycogen synthase kinase 3, known to antagonize Wnt signaling, blocked the neural-crest-inducing activity of Wnt-3a in animal explants and inhibited neural crest formation in whole embryos. We suggest that Wnt-1 and Wnt-3a have a role in patterning the neural tube along its dorsoventral axis and function in the differentiation of the neural crest. C1 NICHHD,GENET MOL LAB,BETHESDA,MD 20892. NCI,VARMUS LAB,NIH,BETHESDA,MD 20892. NR 51 TC 202 Z9 207 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13713 EP 13718 DI 10.1073/pnas.94.25.13713 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500064 PM 9391091 ER PT J AU Wang, YH Russo, TA Kwon, O Chanock, S Rumsey, SC Levine, M AF Wang, YH Russo, TA Kwon, O Chanock, S Rumsey, SC Levine, M TI Ascorbate recycling in human neutrophils: Induction by bacteria SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; H+ SYMPORT PROTEIN; DEHYDROASCORBIC ACID; VITAMIN-C; ESCHERICHIA-COLI; TRANSPORT; EXPRESSION; GALACTOSE; ACCUMULATION; PROTECTION AB Ascorbate (vitamin C) recycling occurs when extracellular ascorbate is oxidized, transported as dehydroascorbic acid, and reduced intracellularly to ascorbate. We investigated microorganism Induction of ascorbate recycling in human neutrophils and in microorganisms themselves. Ascorbate recycling was determined by measuring intracellular ascorbate accumulation. Ascorbate recycling in neutrophils was induced by both Gram-positive and Gram-negative pathogenic bacteria, and the fungal pathogen Candida albicans. Induction of recycling resulted in as high as a 30-fold increase in intracellular ascorbate compared with neutrophils not exposed to microorganisms, Recycling occurred at physiologic concentrations of extracellular ascorbate within 20 min, occurred over a 100-fold range of effector/target ratios, and depended on oxidation of extracellular ascorbate to dehydroascorbic acid. Ascorbate recycling did not occur in bacteria nor in C. albicans, Ascorbate did not enter microorganisms, and dehydroascorbic acid entry was less than could be accounted for by diffusion. Because microorganism recycling reduced dehydroascorbic acid to ascorbate, ascorbate recycling was absent because or negligible entry of the substrate dehydroascorbic acid. Because ascorbate recycling occurs in human neutrophils but: not in microorganisms, it mag represent a eukaryotic defense mechanism against oxidants with possible clinical implications. C1 NIDDKD, MOL & CLIN NUTR SECT, NIH, BETHESDA, MD 20892 USA. SUNY BUFFALO, DEPT MED, BUFFALO, NY 14215 USA. SUNY BUFFALO, DEPT MICROBIOL, BUFFALO, NY 14215 USA. SUNY BUFFALO, CTR MICROBIAL PATHOGENESIS, BUFFALO, NY 14215 USA. NCI, PEDIAT ONCOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 35 TC 65 Z9 66 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13816 EP 13819 DI 10.1073/pnas.94.25.13816 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500083 PM 9391110 ER PT J AU Zhou, YJ Hanson, EP Chen, YQ Magnuson, K Chen, M Swann, PG Wange, RL Changelian, PS OShea, JJ AF Zhou, YJ Hanson, EP Chen, YQ Magnuson, K Chen, M Swann, PG Wange, RL Changelian, PS OShea, JJ TI Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR-BETA-CHAIN; GAMMA SIGNAL-TRANSDUCTION; MICE LACKING JAK3; IL-2 RECEPTOR; LYMPHOID DEVELOPMENT; CRYSTAL-STRUCTURE; INSULIN-RECEPTOR; GENE-EXPRESSION; JANUS KINASE; SRC FAMILY AB Cytokines are critically important for the growth and development of a variety of cells, Janus kinases (JAKs) associate with cytokine receptors and are essential for transmitting downstream cytokine signals. However, the regulation of the enzymatic activity of the JAKs is not well understood. Here, we investigated the role of tyrosine pbosphorylation of JAK3 in regulating its kinase activity by analyzing mutations of tyrosine residues within the putative activation loop of the kinase domain. Specifically, tyrosine residues 980 and 981 of JAK3 were mutated to phenylalanine individually or doubly. We found that JAK3 is autophosphorylated on multiple sites including Y980 and Y981. Compared with the activity of wild-type (WT) JAK3, mutant Y980F demonstrated markedly decreased kinase activity, and optimal phosphorylation of JAK3 on other sites was dependent on Y980 phosphorylation. The mutant Y980F also exhibited reduced phosphorylation of its substrates, gamma c and STAT5A. In contrast, mutant Y981F had greatly increased kinase activity, whereas the double mutant, YY980/9S1FF, had intermediate activity. These results indicate that Y980 positively regulates JAK3 kinase activity whereas Y981 negatively regulates JAK3 kinase activity. These observations in JAK3 are similar to the findings in the kinase that is closely related to the JAK family, ZAP-70; mutations of tyrosine residues within the putative activation loop of ZAP-70 also have opposing actions, Thus, it will be important to determine whether this feature of regulation is unique to JAK3 or if it is also a feature of other JAKs. Given the importance of JAKs and particularly JAK3, it will be critical to fully dissect the positive and negative regulatory function of these and other tyrosine residues in the control of kinase activity and hence cytokine signaling. C1 NIAMSD,SIGNAL TRANSDUCT SECT,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. PFIZER INC,CENT RES,DEPT IMMUNOL,GROTON,CT 06340. RP Zhou, YJ (reprint author), NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892, USA. NR 48 TC 86 Z9 87 U1 2 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 DEC 9 PY 1997 VL 94 IS 25 BP 13850 EP 13855 DI 10.1073/pnas.94.25.13850 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500089 PM 9391116 ER PT J AU Zhong, GM Sousa, CRE Germain, RN AF Zhong, GM Sousa, CRE Germain, RN TI Production, specificity, and functionality of monoclonal antibodies to specific peptide-major histocompatibility complex class II complexes formed by processing of exogenous protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MHC CLASS-II; CELL ANTIGEN RECEPTOR; T-CELL; INVARIANT-CHAIN; MOLECULES; EXPRESSION; TRANSPORT; COMPARTMENTS; SELF; DETERMINANTS AB Several unanswered questions in T cell immunobiology relating to intracellular processing or in vivo antigen presentation could be approached if convenient, specific, and sensitive reagents were available for detecting the peptide-major histocompatibility complex (MHC) class I or class II ligands recognized by alpha beta T cell receptors. For this reason, we have developed a method using homogeneously loaded peptide-MHC class II complexes to generate and select specific mAb reactive with these structures using hen egg lysozyme (HEL) and I-A(k) as a model system. mAbs specific for either HEL-(46-61)-A(k) or HEL-(116-129)-A(k) have been isolated. They cross-react with a small subset of I-A(k) molecules loaded with serf peptides but can nonetheless be used for flow cytometry, immunoprecipitation, Western blotting, and intracellular immunofluorescence to detect specific HEL peptide-MHC class II complexes formed by either peptide exposure or natural processing of native HEL. An example of the utility of these reagents is provided herein by using one of the anti-HEL-(46-61)-A(k) specific mAbs to visualize intracellular compartments where I-A(k) is loaded with HEL-derived peptides early after antigen administration. Other uses, especially for in vivo tracking of specific ligand bearing antigen presenting cells, are discussed. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 122 Z9 122 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13856 EP 13861 DI 10.1073/pnas.94.25.13856 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500090 PM 9391117 ER PT J AU Takemoto, S Mulloy, JC Cereseto, A Migone, TS Patel, BKR Matsuoka, M Yamaguchi, K Takatsuki, K Kamihara, S White, JD Leonard, WJ Waldmann, T Franchini, G AF Takemoto, S Mulloy, JC Cereseto, A Migone, TS Patel, BKR Matsuoka, M Yamaguchi, K Takatsuki, K Kamihara, S White, JD Leonard, WJ Waldmann, T Franchini, G TI Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEUKEMIA-LYMPHOMA VIRUS; MICE LACKING JAK3; GROWTH-FACTOR; BLOOD-CELLS; INTERLEUKIN-4; LYMPHOCYTES; EXPRESSION; PATHWAYS; CYTOKINE; RECEPTOR AB Human T cell leukemia/lymphotropic virus type I (HTLV-I) induces adult T cell leukemia/lymphoma (ATLL). The mechanism of HTLV-I oncogenesis in T cells remains partly elusive. In vitro, HTLV-I induces ligand-independent transformation of human CD4(+) T cells, an event that correlates with acquisition of constitutive phosphorylation of Janus kinases (JAK) and signal transducers and activators of transcription (STAT) proteins. However, it is unclear whether the in vitro model of HTLV-I transformation has relevance to viral leukemogenesis in vivo. Here we tested the status of JAK/STAT phosphorylation and DNA-binding activity of STAT proteins in cell extracts of uncultured leukemic cells from 12 patients with ATLL by either DNA-binding assays, using DNA oligonucleotides specific for STAT-I and STAT-3, STAT-5 and STAT-6 or, more directly, by immunoprecipitation and immunoblotting with anti-phosphotyrosine antibody for JAK and STAT proteins. Leukemic cells from 8 of 12 patients studied displayed constitutive DNA-binding activity of one or more STAT proteins, and the constitutive activation of the JAK/STAT pathway was found to persist over time in the 2 patients followed longitudinally. Furthermore, an association between JAK3 and STAT-I, STAT-3, and STAT-5 activation and cell-cycle progression was demonstrated by both propidium iodide staining and bromodeoxyuridine incorporation in cells of four patients tested. These results imply that JAK/STAT activation is associated with replication of leukemic cells and that therapeutic approaches aimed at JAK/STAT inhibition may be considered to halt neoplastic growth. C1 NCI,MOL & CELLULAR BIOL LAB,DIV CLIN SCI,BETHESDA,MD 20892. NCI,METAB BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892. KUMAMOTO UNIV,SCH MED,DEPT INTERNAL MED 2,KUMAMOTO 860,JAPAN. NAGASAKI UNIV,SCH MED,DEPT LAB MED,NAGASAKI,JAPAN. RP Takemoto, S (reprint author), NCI,BASIC RES LAB,DIV BASIC SCI,37 CONVENT DR,BLDG 37,ROOM 6A11,BETHESDA,MD 20892, USA. OI Takemoto, Shigeki/0000-0003-4130-074X; Matsuoka, Masao/0000-0002-0473-754X NR 43 TC 195 Z9 199 U1 4 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13897 EP 13902 DI 10.1073/pnas.94.25.13897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500097 PM 9391124 ER PT J AU Forns, X Bukh, J Purcell, RH Emerson, SU AF Forns, X Bukh, J Purcell, RH Emerson, SU TI How Escherichia coli can bias the results of molecular cloning: Preferential selection of defective genomes of hepatitis C virus during the cloning procedure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RIBOSOME-BINDING SITE; MESSENGER-RNA; TRANSLATION-INITIATION; HYPERVARIABLE REGION; INTERFERON TREATMENT; GENETIC DRIFT; SEQUENCES; INFECTION; E2/NS1; POPULATIONS AB Cloned PCR products containing hepatitis C virus (HCV) genomic fragments have been used for analyses of HCV genomic heterogeneity and protein expression. These studies assume that the clones derived are representative of the entire virus population and that subsets are not inadvertently selected. The aim of the present study was to express HCV structural proteins. However, we found that there was a strong cloning selection for defective genomes and that most clones generated initially mere incapable of expressing the HCV proteins. The HCV structural region (C-E1-E2-p7) was directly amplified by long reverse transcription-PCR from the plasma of an HCV-infected patient or from a control plasmid containing a viable full-length cDNA of HCV derived from the same patient but cloned in a different vector. The PCR products were cloned into a mammalian expression vector, amplified in Escherichia coli, and tested for their ability to produce HCV structural proteins. Twenty randomly picked clones derived from the HCV-infected patient all contained nucleotide mutations leading to absence or truncation of the expected HCV products. Of 25 clones derived from the control plasmid, only 8% were fully functional for polyprotein synthesis. The insertion of extra nucleotides in the region just upstream of the start codon of the HCV insert led to a statistically significant increase in the number of fully functional clones derived from the patient (42%) and from the control plasmid (72-92%). Nonrandom selection of clones during the cloning procedure has enormous implications for the study of viral heterogeneity, because it can produce a false spectrum of genomic diversity. It can also be an impediment to the construction of infectious viral clones. C1 NIAID,HEPATITIS VIRUSES SECT,LID,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 43 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 DEC 9 PY 1997 VL 94 IS 25 BP 13909 EP 13914 DI 10.1073/pnas.94.25.13909 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500099 PM 9391126 ER PT J AU DebBurman, SK Raymond, GJ Caughey, B Lindquist, S AF DebBurman, SK Raymond, GJ Caughey, B Lindquist, S TI Chaperone-supervised conversion of prion protein to its protease-resistant form SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transmissible spongiform; encephalopathy; aggregation; GroEL; Hsp104 ID SCRAPIE-ASSOCIATED FORM; CELL-FREE CONVERSION; HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONES; PRP; PROPAGATION; COMPLEX; BINDING; STRESS; HSP104 AB Transmissible spongiform encephalopathies (TSEs) are lethal, infectious disorders of the mammalian nervous system. A TSE hallmark is the conversion of the cellular protein PrPC to disease-associated PrPSc (named for scrapie, the first known TSE). PrPC is protease-sensitive, monorneric, detergent soluble, and primarily alpha-helical; PrPSc is protease-resistant, polymerized, detergent insoluble, and rich in beta-sheet. The ''protein-only'' hypothesis posits that PrPSc is the infectious TSE agent that directly converts host-encoded PrPC to fresh PrPSc, harming neurons and creating new agents of infection. To gain insight on the conformational transitions of PrP, we tested the ability of several protein chaperones, which supervise the conformational transitions of proteins in diverse wags, to affect conversion of PrPC to its protease-resistant state, None affected conversion in the absence of pre-existing PrPSc, In its presence, only two, GroEL and Hsp104 (heat shock protein 104), significantly affected conversion, Both promoted it, but the reaction characteristics of conversions sith the two chaperones were distinct, In contrast, chemical chaperones inhibited conversion. Our findings provide new mechanistic insights into nature of PrP conversions, and provide a new set of tools for studying the process underlying TSE pathogenesis. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOL GENET & CELL BIOL,CHICAGO,IL 60637. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,NIH,HAMILTON,MT 59840. NR 44 TC 199 Z9 203 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13938 EP 13943 DI 10.1073/pnas.94.25.13938 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500104 PM 9391131 ER PT J AU Karron, RA Buonagurio, DA Georgiu, AF Whitehead, SS Adamus, JE ClementsMann, ML Harris, DO Randolph, VB Udem, SA Murphy, BR Sidhu, MS AF Karron, RA Buonagurio, DA Georgiu, AF Whitehead, SS Adamus, JE ClementsMann, ML Harris, DO Randolph, VB Udem, SA Murphy, BR Sidhu, MS TI Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro: Clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZA-A VIRUS; PULMONARY HISTOPATHOLOGY; NUCLEOTIDE-SEQUENCE; TYPE-3 PIV3; VACCINE; CHILDREN; GENE; GLYCOPROTEIN; IMMUNIZATION; INFECTIONS AB A live, cold-passaged (cp) candidate vaccine virus, designated respiratory syncytial virus (RSV) B1 cp-52/ 2B5 (cp-52), replicated efficiently in Vero cells, but was found to be overattenuated for RSV-seronegative infants and children. Sequence analysis of reverse-transcription-PCR; amplified fragments of this mutant revealed a large deletion spanning most of the coding sequences for the small hydrophobic (SH) and attachment (G) proteins. Northern blot analysis of cp-52 detected multiple unique read-through mRNAs containing SH and G sequences, consistent with a deletion mutation spanning the SH:G gene junction. Immunological studies confirmed that an intact G glycoprotein was not produced by the cp-52 virus. Nonetheless, cp-52 was infectious and replicated to high titer in tissue culture despite the absence of the viral surface SH and G glycoproteins. Thus, our characterization of this negative-strand RNA virus identified a novel replication-competent deletion mutant lacking two of its three surface glycoproteins. The requirement of SH and G for efficient replication in vivo suggests that selective deletion of one or both of these RSV genes mag provide an alternative or additive strategy for developing an optimally attenuated vaccine candidate. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. WYETH LEDERLE VACCINES & PEDIAT,PEARL RIVER,NY 10965. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. RP Karron, RA (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,DEPT INT HLTH,HAMPTON HOUSE 117,BALTIMORE,MD 21205, USA. OI adamus, jean/0000-0002-0621-7214 FU NIAID NIH HHS [AI-15095] NR 28 TC 265 Z9 284 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 13961 EP 13966 DI 10.1073/pnas.94.25.13961 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500108 PM 9391135 ER PT J AU Brooks, PJ Kleopoulos, SP Funabashi, T Mobbs, CV Pfaff, DW AF Brooks, PJ Kleopoulos, SP Funabashi, T Mobbs, CV Pfaff, DW TI Widespread expression and estrogen regulation of PPEIA-3' nuclear RNA in the rat brain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcription termination; RNA processing; intron; vestibular complex; cerebellar nuclei ID SMALL NUCLEOLAR RNAS; MESSENGER-RNA; INSITU HYBRIDIZATION; HETERONUCLEAR RNA; GENE; TRANSCRIPTION; LOCALIZATION; ELONGATION AB We previously identified a novel nuclear RNA species derived from the preproenkephalin (PPE) gene. This transcript, which we have named PPEIA-3' RNA, hybridizes with probes directed at a region of PPE intron A downstream of an alternative germ-cell transcription start site, but does not contain PPE protein coding sequences. We now report that estrogen treatment of ovariectomized rats increases the expression of conventional PPE heteronuclear RNA, and also induces the expression of PPEIA-3' RNA, apparently in separate cell populations within the ventromedial nucleus of the hypothalamus. Further, we show that cells expressing PPEIA-3' are found in several neuronal groups in the rat forebrain and brainstem, with a distinct topographical distribution. High densities of PPEIA3' containing cells are found in the reticular thalamic nucleus, the basal forebrain, the vestibular complex, the deep cerebellar nuclei, and the trapezoid body, a pattern that parallels the distribution of atypical nuclear RNAs described by other groups. These results suggest that this diverse neuronal population shares a common set of nuclear factors responsible for the expression and retention of this atypical RNA transcript. The implication of these results for cell-specific gene transcription and regulation in the brain and the possible relationship of PPEIA-3' RNA and other atypical nuclear RNAs is discussed. C1 MT SINAI SCH MED,FISHBERG CTR NEUROBIOL,NEW YORK,NY 10128. MT SINAI SCH MED,BRONX VET AFFAIRS MED CTR,NEW YORK,NY 10128. YOKOHAMA CITY UNIV,SCH MED,DEPT PHYSIOL,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,NEW YORK,NY 10021. RP Brooks, PJ (reprint author), NIAAA,MOL NEUROBIOL SECT,NEUROGENET LAB,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 32 TC 2 Z9 2 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 DEC 9 PY 1997 VL 94 IS 25 BP 14037 EP 14041 DI 10.1073/pnas.94.25.14037 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500121 PM 9391148 ER PT J AU Simerly, RB Zee, MC Pendleton, JW Lubahn, DB Korach, KS AF Simerly, RB Zee, MC Pendleton, JW Lubahn, DB Korach, KS TI Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anteroventral periventricular nucleus; hypothalamus; sexual dimorphism; knockout mice; gonadotropin secretion ID ANTEROVENTRAL PERIVENTRICULAR NUCLEUS; TYROSINE-HYDROXYLASE EXPRESSION; TARGETED DISRUPTION; NERVOUS-SYSTEM; MESSENGER-RNA; FEMALE RAT; CYCLIC-AMP; BRAIN; GENE; ANDROGEN AB Although it has been known for some time that estrogen exerts a profound influence on brain development a definitive demonstration of the role of the classical estrogen receptor (ER alpha) in sexual differentiation has remained elusive. In the present study we used a sexually dimorphic population of dopaminergic neurons in the anteroventral periventricular nucleus of the hypothalamus (AVPV) to test the dependence of sexual differentiation on a functional ER alpha by comparing the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the AVPV of wild-type (WT) mice with that of mice in which the ER alpha had been disrupted by homologous recombination (ERKO alpha). Only a few ER alpha-immunoreactive neurons were detected In the AVPV of ERKO alpha mice, and the number of TH-immunoreactive neurons was three times that of WT mice, suggesting that disruption of the ER alpha gene feminized the number of TH-immunoreactive neurons. In contrast, the AVPV contains the same number of TH-immunoreactive neurons in testicular feminized male mice as in WT males, indicating that sexual differentiation of this population of neurons is not dependent on an intact androgen receptor. The number of TH-immunoreactive neurons in the AVPV of female ERKO alpha mice remained higher than that of WT males, but TH staining appeared to be lower than that of WT females. Thus, the sexual differentiation of dopamine neurons in the AVPV appears to be receptor specific and dependent on the perinatal steroid environment. C1 OREGON HLTH SCI UNIV, PROGRAM NEUROSCI, PORTLAND, OR 97201 USA. OREGON HLTH SCI UNIV, DEPT DEV & CELL BIOL, PORTLAND, OR 97201 USA. UNIV MISSOURI, SCH MED, DEPT HUMAN GENET, COLUMBIA, MO 65211 USA. NIEHS, RECEPTOR BIOL SECT, RES TRIANGLE PK, NC 27709 USA. RP Simerly, RB (reprint author), OREGON REG PRIMATE RES CTR, DIV NEUROSCI, 505 NW 185TH AVE, BEAVERTON, OR 97006 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NCRR NIH HHS [K01 RR000163, P51 RR000163, RR00163]; NICHD NIH HHS [P30 HD018185, HD18185, U54 HD018185]; NIMH NIH HHS [MH49236] NR 50 TC 139 Z9 142 U1 0 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 DEC 9 PY 1997 VL 94 IS 25 BP 14077 EP 14082 DI 10.1073/pnas.94.25.14077 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500128 PM 9391155 ER PT J AU Colombo, PJ Wetsel, WC Gallagher, M AF Colombo, PJ Wetsel, WC Gallagher, M TI Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; PKC-GAMMA; MAINTENANCE; ACTIVATION; RECEPTORS; DEFICITS; BRAIN; MICE; IMMUNOREACTIVITY; PHOSPHORYLATION AB Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta(2) and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual B-month-old (n = 13) and 24-month-old (n = 27) male Long-Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKC gamma in the particulate fraction and of PKC beta(2) in the soluble fraction. Aged rats had increased hippocampal PKCy gamma con centrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKC gamma concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKC gamma in a comparison structure, the neostriatum, or for PKC alpha in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKC gamma and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation. C1 NIEHS,LAB SIGNAL TRANSDUCT,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,DURHAM,NC 27710. RP Colombo, PJ (reprint author), JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218, USA. FU NIA NIH HHS [K23 AG000973, P01-AG00973]; NIMH NIH HHS [F32-MH11337, F32 MH011337, K05-MH01149] NR 37 TC 116 Z9 117 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 1997 VL 94 IS 25 BP 14195 EP 14199 DI 10.1073/pnas.94.25.14195 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YK825 UT WOS:A1997YK82500149 PM 9391176 ER PT J AU Billi, AM Matteucci, A Faenza, I Manzoli, L Rubbini, S Gilmour, RS Rhee, SG Cocco, L AF Billi, AM Matteucci, A Faenza, I Manzoli, L Rubbini, S Gilmour, RS Rhee, SG Cocco, L TI Control of expression of PLC beta(1) by LAC repressor system: Relationship between nuclear PLC beta(1) overexpression and growth factor stimulation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SWISS 3T3 CELLS; PHOSPHOLIPASE-C; FRIEND-CELLS; LOCALIZATION; CYCLE; BETA; DNA AB Swiss 3T3 cells have a nuclear phosphoinositide signalling system which is under the control of insulin like growth factor I (IGF-I) and acts separately from that at the plasma membrane. By using the Lac repressor system we were able both to obtain the inducible overexpression of phospholipase C beta(1) (PLC beta(1)) and to determine its subcellular localisation and partitioning. Moreover, by comparing the level of expression at the nucleus and the percentage of cells actively incorporating bromodeoxyuridine (BrdU) in S phase it has strengthened the issue of the importance of this PLC in the onset of DNA synthesis mediated by IGF-I. In addition, this system appears to be a very powerful tool for further analysis of the downstream events following the activation of nuclear PLC beta(1). (C) 1997 Academic Press. C1 Univ Bologna, Inst Human Anat, I-40126 Bologna, Italy. CNR, Citomorphol Inst, I-40136 Bologna, Italy. Ist Ortoped Rizzoli, Lab Cell Biol & Electron Microscopy, I-40136 Bologna, Italy. Univ Auckland, Sch Med, Dept Mol Med, Auckland, New Zealand. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. RP Cocco, L (reprint author), Univ Bologna, Inst Human Anat, Via Irnerio 48, I-40126 Bologna, Italy. NR 16 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 8 PY 1997 VL 241 IS 1 BP 122 EP 126 DI 10.1006/bbrc.1997.7778 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YN258 UT WOS:000071148900021 PM 9405244 ER PT J AU Tierney, JF Stewart, LA Parmar, MKB Fletcher, CDM Jones, G Mosseri, V Patel, M deElvira, MCR Souhami, RL Sylvester, R Tursz, T Alvegard, TA Sigurdsson, H Antman, K Bacchi, M Baker, LH Benjamin, RS Brady, MF Bramwell, V Bui, BN Edmonson, JH Leyvraz, S Omura, GA Rouesse, J Ryan, L vanOosterom, AT Yang, JC AF Tierney, JF Stewart, LA Parmar, MKB Fletcher, CDM Jones, G Mosseri, V Patel, M deElvira, MCR Souhami, RL Sylvester, R Tursz, T Alvegard, TA Sigurdsson, H Antman, K Bacchi, M Baker, LH Benjamin, RS Brady, MF Bramwell, V Bui, BN Edmonson, JH Leyvraz, S Omura, GA Rouesse, J Ryan, L vanOosterom, AT Yang, JC TI Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data SO LANCET LA English DT Article ID RANDOMIZED TRIAL; ONCOLOGY-GROUP; UTERINE SARCOMAS; ACTINOMYCIN-D; ADRIAMYCIN; DOXORUBICIN; CYCLOPHOSPHAMIDE; COMBINATION; EXTREMITIES; RECURRENCE AB Background Individually, randomised trials have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma. Methods A quantitative meta-analysis of updated data from individual patients from all available randomised trials was carried out to assess whether adjuvant chemotherapy improves overall survival, recurrence-free survival, and local and distant recurrence-free intervals (RFI) and whether chemotherapy is differentially effective in patients defined by age, sex, disease status at randomisation, disease site, histology, grade, tumour size, extent of resection, and use of radiotherapy. Findings 1568 patients from 14 trials of doxorubicin-based adjuvant chemotherapy were included (median follow-up 9.4 years). Hazard ratios of 0.73 (95% CI 0.56-0.94, p=0.016) for local RFI, 0.70 (0.57-0.85, p=0.0003) for distant RFI, and 0.75 (0.64-0.87, p=0.0001) for overall recurrence-free survival, correspond to absolute benefits from adjuvant chemotherapy of 6% (95% CI 1-10), 10% (5-15), and 10% (5-15), respectively, at 10 years. For overall survival, the hazard ratio of 0.89 (0.76-1.03) was not significant (p=0.12), but represents an absolute benefit of 4% (1-9) at 10 years. These results were not affected by prespecified changes in the groups of patients analysed. There was no consistent evidence that the relative effect of adjuvant chemotherapy differed for any subgroup of patients for any endpoint. However, the best evidence of an effect of adjuvant chemotherapy for survival was seen in patients with sarcomas of the extremities. Interpretation The meta-analysis provides evidence that adjuvant doxorubicin-based chemotherapy significantly improves the time to local and distant recurrence and overall recurrence-free survival. There is a trend towards improved overall survival. C1 UNIV LUND HOSP, JUBILEUM INST, LUND, SWEDEN. COLUMBIA UNIV, COLUMBIA PRESBYTERIAN MED CTR, NEW YORK, NY 10032 USA. MASSACHUSETTS GEN HOSP, DANA FARBER CANC INST, BOSTON, MA 02114 USA. SIAK COORDINATING CTR, BERN, SWITZERLAND. UNIV MICHIGAN, CTR COMPREHENS CANC, ANN ARBOR, MI 48109 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. ROSWELL PK CANC INST, STAT OFF, GYNECOL ONCOL GRP, BUFFALO, NY USA. CHRISTIE HOSP, MANCHESTER, LANCS, ENGLAND. INST BERGONIE, BORDEAUX, FRANCE. MAYO CLIN, ROCHESTER, MN USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. IST ORTOPED RIZZOLI, BOLOGNA, ITALY. HAMILTON REG CANC CTR, HAMILTON, ON L8V 1C3, CANADA. UNIV LAUSANNE HOSP, LAUSANNE, SWITZERLAND. SWISS GRP CLIN CANC RES, BERN, SWITZERLAND. INST CURIE, DEPT BIOSTAT, PARIS, FRANCE. UNIV ALABAMA, BIRMINGHAM, AL USA. CTR RENE HUGUENIN, ST CLOUD, FRANCE. UCL, EUROPEAN GRP BLOOD & MARROW TRANSPLANTAT, LONDON, ENGLAND. DANA FARBER CANC INST, STAT OFF, EASTERN COOPERAT ONCOL GRP, BOSTON, MA 02115 USA. UCL, SCH MED, DEPT ONCOL, LONDON W1N 8AA, ENGLAND. EORTC DATA CTR, METAANAL UNIT, BRUSSELS, BELGIUM. INST GUSTAVE ROUSSY, VILLEJUIF, FRANCE. UNIV ZIEKENHUIZEN, DEPT ONCOL, LOUVAIN, BELGIUM. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NR 38 TC 450 Z9 469 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD DEC 6 PY 1997 VL 350 IS 9092 BP 1647 EP 1654 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YK211 UT WOS:A1997YK21100008 ER PT J AU Daly, S Mills, JL Molloy, AM Conley, M Lee, YJ Kirke, PN Weir, DG Scott, JM AF Daly, S Mills, JL Molloy, AM Conley, M Lee, YJ Kirke, PN Weir, DG Scott, JM TI Minimum effective dose of folic acid for food fortification to prevent neural-tube defects SO LANCET LA English DT Article ID SUPPLEMENTATION AB Background Although a daily supplement of 400 mu g folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 mu g. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 mu g/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. Methods We screened 323 women. 172 with red-cell folate between 150 mu g/L and 400 mu g/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 mu g, 200 mu g, or 400 mu g daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. Findings There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 mu g/L (95% CI 43-120) and 375 mu g/L (354-444) in the 100 mu g/day group, 130 mu g/L (108-184) and 475 mu g/L (432-503) in the 200 mu g/day group, and 200 mu g/L (125-312) and 571 mu g/L(481-654) in the 400 mu g/day group. Interpretation A fortification programme that delivered 400 mu g folio acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 mu g daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 mu g daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD. C1 COOMBE WOMENS HOSP,RCSI DEPT,DUBLIN,IRELAND. NICHHD,EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NICHHD,BRANCH STAT,NIH,BETHESDA,MD 20892. TRINITY COLL DUBLIN,DEPT CLIN MED,DUBLIN,IRELAND. TRINITY COLL DUBLIN,DEPT BIOCHEM,DUBLIN,IRELAND. HLTH RES BOARD,DUBLIN,IRELAND. NR 16 TC 171 Z9 180 U1 0 U2 14 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 6 PY 1997 VL 350 IS 9092 BP 1666 EP 1669 DI 10.1016/S0140-6736(97)07247-4 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YK211 UT WOS:A1997YK21100011 PM 9400511 ER PT J AU Robbins, JB Schneerson, R Gotschlich, EC AF Robbins, JB Schneerson, R Gotschlich, EC TI Meningococcal vaccine in sub-Saharan Africa - Reply SO LANCET LA English DT Letter ID DURATION; AGE RP Robbins, JB (reprint author), NIH,DEPT HLTH & HUMAN SERV,BLDG 10,BETHESDA,MD 20892, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 6 PY 1997 VL 350 IS 9092 BP 1709 EP 1710 DI 10.1016/S0140-6736(05)64317-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YK211 UT WOS:A1997YK21100062 ER PT J AU Benkirane, M Jin, DY Chun, RF Koup, RA Jeang, KT AF Benkirane, M Jin, DY Chun, RF Koup, RA Jeang, KT TI Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5 Delta 32 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-LINE; RECEPTOR; ENTRY; GENE; LESTR/FUSIN; MIP-1-ALPHA; INDIVIDUALS; PROGRESSION; REPLICATION; MIP-1-BETA AB Human chemokine receptor 5 (CCRB) functions as a co-receptor for Human immunodeficiency virus (HIV-1) infection, CCR5 is a seven-transmembrane cell surface receptor, Recently, a naturally occurring mutation of CCRB, ccr5 Delta 32, has been described, A small number of Caucasians are homozygously ccr5 Delta 32/ccr5 Delta 32, while a larger number of individuals are heterozygously CCR5/ccr5 Delta 32. The ccr5 Delta 32/ccr5 Delta 32 genotype has been linked to a phenotype that is "highly" protected from HIV-1 infection, On the other hand, several studies have shown that the CCR5/ccr5 Delta 32 genotype confers "relative" protection from AIDS with onset of disease being delayed by 2-4 years, Although it is known that peripheral blood lymphocytes from heterozygous individuals (CCR5/ccr5 Delta 32) support ex vivo HTV-1 replication at a reduced level compared with CCR5/CCR5 cells, the molecular basis for this observation is unknown, Here we report on events that post-translationally modify CCRB, We show that CCR5 progresses through the endoplasmic reticulum prior to appearing on the cell surface, Mature CCRB can be post-translationally modified by phosphorylation and/or co-translationally by multimerization, By contrast, mutant ccr5 Delta 32, although retaining the capacity for multimerization, was incapable of being phosphorylated. ccr5 Delta 32 heterocomplexes with CCR5, and this interaction retains CCR5 in the endoplasmic reticulum resulting in reduced cell surface expression, Thus, co-expression in cells of ccr5 Delta 32 with CCR5 produces a trans-inhibition by the former of ability by the latter to support HIV-1 infection, Taken together, our findings suggest CCR5/ccr5 Delta 32 heterodimerization as a molecular explanation for the delayed onset of AIDS in CCR5/ccr5 Delta 32 individuals. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis, Dallas, TX 75235 USA. Ctr Rech Biochim Macromol, CNRS, ERS 0155, Montpellier, France. RP Benkirane, M (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008; Chun, Rene/A-9415-2010 OI Chun, Rene/0000-0002-0190-0807 FU NIAID NIH HHS [AI35522, AI42397] NR 27 TC 274 Z9 279 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 30603 EP 30606 DI 10.1074/jbc.272.49.30603 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800004 PM 9388191 ER PT J AU Zhang, P Liu, B Kang, SW Seo, MS Rhee, SG Obeid, LM AF Zhang, P Liu, B Kang, SW Seo, MS Rhee, SG Obeid, LM TI Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bcl-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; SACCHAROMYCES-CEREVISIAE; CELL-DEATH; FACTOR ADF; GENE; INDUCTION; REDUCTASE; CANCER; YEAST; LOCALIZATION AB Thioredoxin peroxidase (TPx) is a member of a newly discovered family of proteins that are conserved from yeast to mammals and to which natural killer enhancing factor belongs. These proteins are antioxidants that function as peroxidases only when coupled to a sulfhydryl reducing system, The physiological function of TPx in cells is not yet known, Here we demonstrate that when the human TPx II, a member of this family, is stably overexpressed in Molt-4 leukemia cells, it protects from apoptosis induced by serum deprivation, ceramide, or etoposide. TPx II, like Bcl-2, is able to inhibit release of cytochrome c from mitochondria to cytosol, and it inhibits lipid peroxidation in cells, TPx II, unlike Bcl-2, could prevent hydrogen peroxide accumulation in cells, suggesting that it functions upstream of Bcl-2 in the protection from apoptosis and may be implicated as an endogenous regulator of apoptosis. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Vet Affairs Geriatr Res Educ & Clin Ctr, Durham, NC 27710 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Obeid, LM (reprint author), Duke Univ, Med Ctr, Dept Med, Box3345, Durham, NC 27710 USA. OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [1R29-AG-12467] NR 41 TC 301 Z9 305 U1 3 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 30615 EP 30618 DI 10.1074/jbc.272.49.30615 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800007 PM 9388194 ER PT J AU Toretsky, JA Kalebic, T Blakesley, V LeRoith, D Helman, LJ AF Toretsky, JA Kalebic, T Blakesley, V LeRoith, D Helman, LJ TI The insulin-like growth factor-I receptor is required for EWS/FLI-1 transformation of fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUND-CELL TUMORS; DNA-BINDING; TRANSCRIPTIONAL ACTIVATOR; T(1122) TRANSLOCATION; CHIMERIC TRANSCRIPTS; EWING SARCOMA; GENE; PROTEIN; FUSION; PHOSPHATASE AB Ewing's family of tumors is characterized by a well described reciprocal translocation, t(11;22)(q24;q12), which produces a fusion protein (EWS/FLI-1) that transforms mouse fibroblasts. The EWS/FLI-1 fusion protein has been shown to act as a potent chimeric transcription factor. Overexpression of insulin like growth factor-I receptor (IGF-IR) has been implicated in many tumor models as playing a role in cell growth and tumorigenesis. In addition, blockade of the IGF-IR inhibits the growth of Ewing's family of tumors cells. Therefore, we first studied whether the presence of the IGF-IR is required for transformation by the EWS/FLI-1 fusion protein. To perform this study, we used two previously described fibroblast cell lines, R- and W, derived from an IGF-IR knockout mouse and a wild-type littermate, respectively. Neither W nor R-cells without the fusion protein formed soft agar colonies. However, W clones expressing the fusion message (WF cells) formed soft agar colonies, whereas R-clones expressing the fusion message (R-F cells) did not form soft agar colonies. Because the IGF-IR is required for EWS/FLI-1 transformation, we chose to investigate whether altered signaling occurs from the IGF-IR when the EWS/FLI-1 fusion is present. WF cells demonstrated a greater degree of ligand-stimulated insulin receptor substrate-1 phosphorylation when compared with W cells, suggesting that expression of the EWS/FLI-1 fusion protein alters the IGF-IR signaling pathway. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Toretsky, JA (reprint author), Univ Maryland, Dept Pediat Hematol Oncol, 22 S Greene St,Rm N5E16, Baltimore, MD 21201 USA. EM jt@helix.nih.gov NR 40 TC 151 Z9 157 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 30822 EP 30827 DI 10.1074/jbc.272.49.30822 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800038 PM 9388225 ER PT J AU Jin, DY Chae, HZ Rhee, SG Jeang, KT AF Jin, DY Chae, HZ Rhee, SG Jeang, KT TI Regulatory role for a novel human thioredoxin peroxidase in NF-kappa B activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; THIOL-SPECIFIC ANTIOXIDANT; ALKYL HYDROPEROXIDE REDUCTASE; LONG TERMINAL REPEAT; TRANSCRIPTION FACTOR; REDOX REGULATION; BINDING-PROTEIN; CLONING; CELLS; GENE AB Reduction-oxidation (redox) plays a critical role in NF-kappa B activation. Diverse stimuli appear to utilize reactive oxygen species (e.g. hydrogen peroxide) as common effecters for activating NF-kappa B. Antioxidants govern intracellular redox status, and many such molecules can reduce H2O2.,, However, functionally, it does appear that different antioxidants are variously selective for redox regulation of certain transcription factors such as NF-kappa B, For NF-kappa B, thioredoxin has been described to be a more potent antioxidant than either glutathione or N-acetylcysteine. Thioredoxin peroxidase is the immediate enzyme that links reduction of H2O2, to thioredoxin. Several putative human thioredoxin peroxidases have been identified using recursive sequence searches/ alignments with yeast or prokaryotic enzymes. None has been characterized in detail for intracellular function(s), Here, we describe a new human thioredoxin peroxidase, antioxidant enzyme AOE372, identified by virtue of its protein-protein interaction with the product of a proliferation association gene, pag, which is also a thiol specific antioxidant, In human cells, AOE372 defines a redox pathway that specifically regulates NF-kappa B activity via a modulation of I kappa B-alpha phosphorylation in the cytoplasm, We show that AOE372 activity is regulated through either home-or heterodimerization with other thiol peroxidases, implicating subunit assortment as a mechanism for regulating antioxidant specificities, AOE372 function suggests thioredoxin peroxidase as an immediate regulator of H2O2-mediated activation of NF-kappa B. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 54 TC 313 Z9 325 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 30952 EP 30961 DI 10.1074/jbc.272.49.30952 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800055 PM 9388242 ER PT J AU Lee, FJS Huang, CF Yu, WL Buu, LM Lin, CY Huang, MC Moss, J Vaughan, M AF Lee, FJS Huang, CF Yu, WL Buu, LM Lin, CY Huang, MC Moss, J Vaughan, M TI Characterization of an ADP-ribosylation factor-like 1 protein in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; PHOSPHOLIPASE-D ACTIVITY; CHOLERA-TOXIN; GOLGI MEMBRANES; NUCLEOTIDE-BINDING; ARF PROTEINS; FACTOR-I; SELECTIVE AMPLIFICATION; DROSOPHILA-MELANOGASTER; ENDOPLASMIC-RETICULUM AB ADP-ribosylation factors (ARFs) are highly conserved similar to 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are believed to participate in vesicular transport in both exocytic and endocytic pathways. Several ARF-like proteins (ARLs) have been cloned from Drosophila, rat, and human; however, the biological functions of ARLs are unknown. We have identified a yeast gene (ARL1) encoding a protein that is structurally related (>60% identical) to human, rat, and Drosophila ARL1. Biochemical analyses of purified recombinant yeast ARL1 (yARL1) protein revealed properties similar to those ARF and ARL1 proteins, including the ability to bind and hydrolyze GTP. Like other ARLs, recombinant yARL1 protein did not stimulate cholera toxin-catalyzed auto-ADP-ribosylation. yARL1 was not recognized by antibodies against mammalian ARLs or yeast ARFs. Anti-yARL1 antibodies did not cross-react with yeast ARFs, but did react with human ARLs. On subcellular fractionation, yARL1, similar to yARF1, was localized to the soluble fraction. The amino terminus of yARL1, like that of ARF, was myristoylated. Unlike Drosophila Arl1, yeast ARL1 was not essential for cell viability. Like rat ARL1, yARL1 might be associated in part with the Golgi complex. However, yARL1 was not required for endoplasmic reticulum-to-Golgi protein transport, and it may offer an opportunity to define an ARL function in another kind of vesicular trafficking, such as the regulated secretory pathway. C1 Natl Taiwan Univ, Sch Med, Inst Mol Med, Taipei 10764, Taiwan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Lee, FJS (reprint author), Natl Taiwan Univ, Sch Med, Inst Mol Med, 7 Chung Shan S Rd, Taipei 10764, Taiwan. OI LEE, FANG-JEN/0000-0002-2167-2426; HUANG, MIN-CHUAN/0000-0002-0704-3447 NR 78 TC 60 Z9 63 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 30998 EP 31005 DI 10.1074/jbc.272.49.30998 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800061 PM 9388248 ER PT J AU Sagawa, K Kimura, T Swieter, M Siraganian, RP AF Sagawa, K Kimura, T Swieter, M Siraganian, RP TI The protein-tyrosine phosphatase SHP-2 associates with tyrosine-phosphorylated adhesion molecule PECAM-1 (CD31) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; GROWTH-FACTOR RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; FC-GAMMA-RIIB; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; SH2 DOMAINS; MONOCLONAL-ANTIBODIES; MAST-CELL; IN-VIVO AB Aggregation of many cell-surface receptors results in tyrosine phosphorylation of numerous proteins. We previously observed the tyrosine phosphorylation of the platelet/endothelial cell adhesion molecule, PECAM-1 (CD31), after Fc epsilon RI stimulation in rat basophilic leukemia RBL-2H3 cells. Here we found that PECAM-1 was also transiently tyrosine-phosphoryated after adherence of these cells to fibronectin, Similarly aggregation of the T cell receptor on Jurkat cells also induced this tyrosine phosphorylation, The protein-tyrosine phosphatase SHP-2 is a widely expressed cytosolic enzyme with two Src homology 2 (SH2) domains. SHP-2, but not the related protein-tyrosine phosphatase SHP-1, associated with PECAM-1. This association of the two proteins correlated with the extent of the tyrosine phosphorylation of PECAM-1. A fusion protein containing the two SH2 domains of SHP-2 precipitated PECAM-1 from cell lysates and also directly bound to phosphorylated PECAM-1, In immune precipitate phosphatase assays, there was tyrosine dephosphorylation of PECAM-1, Therefore, integrin and immune receptor activation results in tyrosine phosphorylation of PECAM-1 and the binding of the protein-tyrosine phosphatase SHP-2, which could regulate receptor-mediated signaling in cells. C1 NIDR, Receptors & Signal Transduct Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Siraganian, RP (reprint author), NIDR, Receptors & Signal Transduct Sect, OIIB, NIH, Bldg 10,Rm 1N106, Bethesda, MD 20892 USA. EM rs53x@nih.gov NR 66 TC 91 Z9 91 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 31086 EP 31091 DI 10.1074/jbc.272.49.31086 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800073 PM 9388260 ER PT J AU Ueda, A Ishigatsubo, Y Okubo, T Yoshimura, T AF Ueda, A Ishigatsubo, Y Okubo, T Yoshimura, T TI Transcriptional regulation of the human monocyte chemoattractant protein-1 gene - Cooperation of two NF-kappa B sites and NF-kappa B/Rel subunit specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IDIOPATHIC PULMONARY FIBROSIS; GROWTH-FACTOR INDUCTION; TUMOR-NECROSIS-FACTOR; IFN-BETA GENE; MESSENGER-RNA; P65 SUBUNIT; ATHEROSCLEROTIC LESIONS; VIRUS INDUCTION; E-SELECTIN; CELL-LINE AB Human monocyte chemoattractant protein-1 (human MCP-1) mRNA accumulated in THP-1 cells 2 h after lipopolysaccharide (LPS) stimulation, DNase I footprinting revealed that LPS stimulation induced protein binding to the two closely located NF-kappa B sites, A1 and A2, By electrophoretic gel mobility shift assay and supershift assay, the binding of (p65)(2), c-Rel/p65, p50/p65, and p50/c-Rel to the A2 oligonucleotide probe was detected after LPS stimulation, In contrast, 12-o-tetradecanoylphorbol 13-acetate did not induce a significant amount of MCP-1 mRNA in THP-1 cells 2 h after stimulation, and only p50/p65 bound to the A2 probe, trans Activity of each NF-kappa B/Rel dimer was investigated by transfecting P19 cells with p65, p50, and/or c-Rel expression vectors, and a luciferase construct containing the enhancer region of the human MCP-1 gene, Expression of recombinant p65 or p65 and c-Rel resulted in elevated luciferase activities, indicating that (p65)(2) and c-Rel/p65 had trans-activity, The binding of (p65)(2) and/or c-Rel/p65 to the A2 probe was also detected from 12-o-tetradecanoylphorbol 13-acetate-stimulated HeLa, HOS, and A172 cells in which expression of MCP-1 mRNA was elevated. Finally, the role of the Al site was investigated, Both (p65)(2) and c-Rel/p65 bound to the Al probe by electrophoretic mobility shift assay and a mutation in the A1 or A2 site resulted in a loss of the enhancer activity, These results suggest that the binding of (p65)(2) and c-Rel/p65 to the A1 and A2 sites of this gene is important for the tissue-and stimulus-specific transcription of the human MCP-1 gene. C1 NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunobiol Lab, Frederick, MD 21702 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. RP Yoshimura, T (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunobiol Lab, Bldg 560,Rm 12-71, Frederick, MD 21702 USA. EM yoshimur@ncifcrf.gov NR 53 TC 249 Z9 252 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1997 VL 272 IS 49 BP 31092 EP 31099 DI 10.1074/jbc.272.49.31092 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT745 UT WOS:000071640800074 PM 9388261 ER PT J AU Chikuma, T Kishii, M Taguchi, K Yajima, R Kato, T Loh, YP Ishii, Y Tanaka, A AF Chikuma, T Kishii, M Taguchi, K Yajima, R Kato, T Loh, YP Ishii, Y Tanaka, A TI High-performance liquid chromatographic colorimetric assay for glycine carboxypeptidase activity SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE glycine carboxypeptidase; enzymes ID ALPHA-AMIDATING MONOOXYGENASE; PURIFICATION; PRECURSOR; PITUITARY AB A rapid and sensitive assay method for the determination of glycine carboxypeptidase activity has been reported. This method is based on the monitoring of the absorption at 460 nm of 4-dimethylaminoazobenzene-4'-sulfonyl-G-L-Phe, enzymatically formed from the substrate 4-dimethylaminoazobenzene-4'-sulfonyl-Gly-L-Phe-Gly, after separation by high-performance liquid chromatography (HPLC) using a TSK gel ODS-80TM reversed-phase column by isocratic elution. This method is sensitive enough to measure 4-dimethylaminoazobenzene-4'-sulfonyl-Gly-L-Phe at concentrations as low as 1 pmol and yield highly reproducible results and requires less than 7.5 min per sample for separation and quantitation. The pH optimum for glycine carboxypeptidase activity was 4.8 to 5.4. The K-m and V-max values were respectively 21.1 mu mol and 3.73 pmol/mu g/h with the use of enzyme extract obtained from bovine pituitary: Glycine carboxypeptidase activity was strongly inhibited by Ag+, Cu2+ and p-chloromercuriphenylsulfonic acid. Among the organs examined in a mouse, the highest specific activity of the enzyme was found in testis. The sensitivity and selectivity of this method will aid in efforts to examine the physiological role of this peptidase. (C) 1997 Elsevier Science B.V. C1 Showa Coll Pharmaceut Sci, Dept Pharmaceut Analyt Chem, Tokyo 194, Japan. Showa Coll Pharmaceut Sci, Dept Pharmacotherapeut, Tokyo 194, Japan. Dainabot Co, Ctr Res & Dev, Chiba 271, Japan. Yokohama City Univ, Lab Mol Recognit, Grad Sch Integrated Sci, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Chikuma, T (reprint author), Showa Coll Pharmaceut Sci, Dept Pharmaceut Analyt Chem, 3-3165 Higashi Tamagawagakuen, Tokyo 194, Japan. NR 16 TC 1 Z9 1 U1 0 U2 0 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 PD DEC 5 PY 1997 VL 703 IS 1-2 BP 45 EP 51 DI 10.1016/S0378-4347(97)00413-1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YP858 UT WOS:000071322900006 PM 9448061 ER PT J AU Shelby, MD Tice, RR Witt, KL AF Shelby, MD Tice, RR Witt, KL TI 17-beta-estradiol fails to induce micronuclei in the bone marrow cells of rodents SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE cytogenetics; hormone; estrogen ID IN-VIVO; GENOTOXICITY; ESTROGEN C1 NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst, Res Triangle Pk, NC 27709 USA. Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. RP Shelby, MD (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD DEC 5 PY 1997 VL 395 IS 1 BP 89 EP 90 DI 10.1016/S1383-5718(97)00148-4 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YQ676 UT WOS:000071412100009 PM 9465917 ER PT J AU Spearing, MK Post, RM Leverich, GS Brandt, D Nolen, W AF Spearing, MK Post, RM Leverich, GS Brandt, D Nolen, W TI Modification of the Clinical Global Impressions (CGI) scale for use in bipolar illness (BP): the CGI-BP SO PSYCHIATRY RESEARCH LA English DT Article DE methodology; global ratings; mental disorder; manic-depressive illness ID AFFECTIVE-DISORDERS; PATTERN-ANALYSIS; DOUBLE-BLIND; FLUOXETINE; PREDICTORS; EFFICACY; CARBAMAZEPINE; RELIABILITY; DEPRESSION; DEMENTIA AB The Clinical Global Impressions Scale (CGI) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder. Criticisms of the original CGI were addressed by correcting inconsistencies in scaling, identifying time frames for comparison, clarifying definitions of illness severity and change, and separating out assessment of treatment side effects from illness improvement during treatment. A Detailed User's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version (CGI-BP) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania, depression, and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis. Interrater reliability of the scale was demonstrated in preliminary analyses. Thus, the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder. (C) 1997 Elsevier Science Ireland Ltd. C1 NIMH, BPB, NIH, Bethesda, MD 20892 USA. Stanley Fdn Bipolar Network, Bethesda, MD 20814 USA. HC Rumke Grp, NL-3500 AB Utrecht, Netherlands. RP Post, RM (reprint author), NIMH, BPB, NIH, Bldg 10,Room 3N212, Bethesda, MD 20892 USA. RI Nolen, Willem/E-9006-2014 NR 29 TC 586 Z9 596 U1 3 U2 11 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 5 PY 1997 VL 73 IS 3 BP 159 EP 171 DI 10.1016/S0165-1781(97)00123-6 PG 13 WC Psychiatry SC Psychiatry GA YT930 UT WOS:000071660800004 PM 9481807 ER PT J AU Guo, SW Zheng, CJ Li, CC AF Guo, SW Zheng, CJ Li, CC TI ''Gene war of the century''? SO SCIENCE LA English DT Letter C1 UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55454. NIDOCD,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15261. RP Guo, SW (reprint author), UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55454, USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 5 PY 1997 VL 278 IS 5344 BP 1693 EP 1694 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ901 UT WOS:A1997YJ90100003 PM 9411783 ER PT J AU Sheng, HZ Moriyama, K Yamashita, T Li, H Potter, SS Mahon, KA Westphal, H AF Sheng, HZ Moriyama, K Yamashita, T Li, H Potter, SS Mahon, KA Westphal, H TI Multistep control of pituitary organogenesis SO SCIENCE LA English DT Article ID HOMEOBOX GENE LHX3; HOMEODOMAIN FACTOR; PIT-1; LIM; EXPRESSION AB Lhx3 and Lhx4 (Gsh4), two closely related LIM homeobox genes, determine formation of the pituitary gland in mice. Rathke's pouch is formed in two steps-first as a rudiment and later as a definitive pouch. Lhx3 and Lhx4 have redundant control over formation of the definitive pouch. Lhx3 controls a subsequent step of pituitary fate commitment. Thereafter, Lhx3 and Lhx4 together regulate proliferation and differentiation of pituitary-specific cell lineages. Thus, Lhx3 and Lhx4 dictate pituitary organ identity by controlling developmental decisions at multiple stages of organogenesis. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ANAT,IZUMO,SHIMANE 693,JAPAN. ACAD SINICA,INST MOL BIOL,TAIPEI 11529,TAIWAN. UNIV CINCINNATI,COLL MED,CHILDRENS HOSP RES FDN,CINCINNATI,OH 45229. UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CINCINNATI,OH 45229. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 18 TC 264 Z9 264 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 5 PY 1997 VL 278 IS 5344 BP 1809 EP 1812 DI 10.1126/science.278.5344.1809 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ901 UT WOS:A1997YJ90100052 PM 9388186 ER PT J AU Rick, SW Berne, BJ AF Rick, SW Berne, BJ TI Free energy of the hydrophobic interaction from molecular dynamics simulations: The effects of solute and solvent polarizability SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID EFFECTIVE PAIR POTENTIALS; CHARGE FORCE-FIELDS; COMPUTER-SIMULATION; LIQUID WATER; METHANE DIMER; HYDRATION; TEMPERATURE; CONSTANT; EQUALIZATION; ASSOCIATION AB Molecular dynamics simulations are used to calculate the free energy of methane association in water, using the polarizable fluctuating charge model that treats the charges on atomic sites as dynamical variables. Compared with previous studies using nonpolarizable potentials, the inclusion of polarizability leads only ro small differences in the methane pair potential of mean force. This is in contradistinction to two previous studies using other polarizable models, which do not agree with the nonpolarizable results or with each other. The potential of mean force is calculated at three different temperatures (283, 298, and 313 K) from which the temperature dependence and also the entropic part of the free energy is examined. It is found that the tendency for methane molecules to aggregate increases with increasing temperature and that aggregation is stablized by entropy. C1 COLUMBIA UNIV, DEPT CHEM, NEW YORK, NY 10027 USA. COLUMBIA UNIV, CTR BIOMOL SIMULAT, NEW YORK, NY 10027 USA. NCI, FREDERICK BIOMED SUPERCOMP CTR, SAIC FREDERICK, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 57 TC 92 Z9 93 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 4 PY 1997 VL 101 IS 49 BP 10488 EP 10493 DI 10.1021/jp971579z PG 6 WC Chemistry, Physical SC Chemistry GA YK291 UT WOS:A1997YK29100046 ER PT J AU Bose, S Mukhopadyay, AK Dracheva, S Hendler, RW AF Bose, S Mukhopadyay, AK Dracheva, S Hendler, RW TI Role of salt in reconstituting photocycle behavior in triton-damaged purple membranes by addition of native lipids SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SURFACE-CHARGE DENSITY; BACTERIORHODOPSIN PHOTOCYCLE; BINDING-SITES; CATION-BINDING; CA2+ BINDING; SCHIFF-BASE; PH; DEPROTONATION; POTENTIALS; TRANSITION AB We demonstrated recently that damage to the normal bacteriorhodopsin (BR) photocycle caused by brief exposure to dilute Triton X-LOO, which removes lipids from the membrane, can be repaired by adding back an extract of purple membrane (PM) lipids (Dracheva; et al. FEES Lett. 1996, 386, 209). It was shown that reconstitution with lipids required the presence of a high concentration of NaCl (similar to 0.5 M for half-maximal reconstitution). This paper shows that reconstitution can be achieved with divalent and trivalent cations at much lower concentrations than were required for NaCl (i.e. similar to 7.5 mM for Ca2+ and similar to 0.15 mM for La3+ for half-maximal reconstitution), indicating that negative surface charges must be neutralized to allow the added lipids to reach and be incorporated at the proper locus. We also report here that reconstitution in the absence of added salt can be accomplished by protons alone with an apparent pK near 5. The role of salt involves both charge-screening and specific binding. It was found that, contrary to the prediction of the Gouy-Chapmann equation, the pK(app) for reconstitution rises with increasing salt concentration. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 28 TC 7 Z9 7 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 4 PY 1997 VL 101 IS 49 BP 10584 EP 10587 DI 10.1021/jp972260h PG 4 WC Chemistry, Physical SC Chemistry GA YK291 UT WOS:A1997YK29100058 ER PT J AU Hess, RA Bunick, D Lee, KH Bahr, J Taylor, JA Korach, KS Lubahn, DB AF Hess, RA Bunick, D Lee, KH Bahr, J Taylor, JA Korach, KS Lubahn, DB TI A role for oestrogens in the male reproductive system SO NATURE LA English DT Article ID ESTROGEN-RECEPTOR GENE; DUCTULI-EFFERENTES; SPERM COUNTS; EPIDIDYMIS; TESTIS; MOUSE; RAT; DISRUPTION; SECRETION; ESTRADIOL AB Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However,both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml(-1) in rete testis fluids(1,2), which is higher than serum oestradiol in the female(3). It is well known that male reproductive tissues express oestrogen receptors(4-7), but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts(8,9). C1 UNIV ILLINOIS,DEPT ANIM SCI,URBANA,IL 61801. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65211. NIEHS,RES TRIANGLE PK,NC 27709. RP Hess, RA (reprint author), UNIV ILLINOIS,DEPT VET BIOSCI,2001 S LINCOLN AVE,URBANA,IL 61802, USA. OI Korach, Kenneth/0000-0002-7765-418X FU FIC NIH HHS [F06 TW002317] NR 31 TC 605 Z9 630 U1 4 U2 36 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 4 PY 1997 VL 390 IS 6659 BP 509 EP 512 DI 10.1038/37352 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ865 UT WOS:A1997YJ86500051 PM 9393999 ER PT J AU Busettini, C Masson, GS Miles, FA AF Busettini, C Masson, GS Miles, FA TI Radial optic flow induces vergence eye movements with ultra-short latencies SO NATURE LA English DT Article ID OCULAR-FOLLOWING RESPONSES; SUPERIOR TEMPORAL AREA; MACAQUE MONKEY; EXPANSION CONTRACTION; ROTATION CELLS; SELF-MOTION; DORSAL PART; MST NEURONS; DEPENDENCE; DIRECTION AB An observer moving forwards through the environment experiences a radial pattern of image motion on each retina, Such patterns of optic now are a potential source of information about the observer's rate of progress(1), direction of heading(2) and time to reach objects that lie ahead(3). As the viewing distance changes there must be changes in the vergence angle between the two eyes so that both foveas remain aligned on the object of interest in the scene ahead. Here we show that radial optic flow can elicit appropriately directed (horizontal) vergence eye movements with ultra-short latencies (roughly 80 ms) in human subjects. Centrifugal flow, signalling forwards motion, increases the vergence angle, whereas centripetal now decreases the vergence angle. These vergence eye movements are still evident when the observer's view of the flow pattern is restricted to the temporal hemifield of one eye, indicating that these responses do not result from anisotropies in motion processing but from a mechanism that senses the radial pattern of now. We hypothesize that flow-induced vergence is but one of a family of rapid ocular reflexes, mediated by the medial superior temporal cortex, compensating for translational disturbance of the observer. C1 NEI, SENSORIMOTOR RES LAB, NIH, BETHESDA, MD 20892 USA. RI MASSON, Guillaume/G-4615-2012 NR 30 TC 60 Z9 61 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 4 PY 1997 VL 390 IS 6659 BP 512 EP 515 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ865 UT WOS:A1997YJ86500052 PM 9394000 ER PT J AU Matsuda, T Sasaki, M Kato, H Yamada, H Cohen, M Barrett, JC Oshimura, M Wake, N AF Matsuda, T Sasaki, M Kato, H Yamada, H Cohen, M Barrett, JC Oshimura, M Wake, N TI Human chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma SO ONCOGENE LA English DT Article DE tumor suppressor gene; choriocarcinoma; chromosome 7; homozygous deletion ID HUMAN ENDOGENOUS RETROVIRUS; PRIMARY BREAST-CANCER; CARCINOMA CELL-LINE; HYDATIDIFORM MOLE; SQUAMOUS-CELL; MESSENGER-RNAS; TUMORIGENIC EXPRESSION; PANCREATIC-CARCINOMA; HOMOZYGOUS DELETIONS; FREQUENT LOSS AB Choriocarcinoma developed from a complete hydatidiform mole has an unique genetic feature that involves monoallelic contribution from the paternal genome, To the chromosome carrying putative tumor gene(s), microcell-hybrids were isolated following fusion of choriocarcinoma cells with microcells from mouse A9 cells containing a single human chromosome (1, 2, 6, 7, 9 or 11), Microcell-hybrids with the introduction of chromosome 7 were suppressed or modulated for tumorigenicity and exhibited altered in vitro growth properties, Introduction of chromosomes 1, 2, 6, 9 or 11 had no effect, Tumorigenic revertants isolated from microcell-hybrids with the introduced chromosome 7 contains reduced numbers of chromosome 7, These findings suggest that chromosome 7 contains a putative tumor suppressor gene(s) for choriocarcinoma, Alterations in tumorigenic phenotypes seen in microcell-hybrids were not associated with the presence of either ERV3 or H-plk locus located on the introduced chromosome 7, indicating the putative tumor suppressor gene(s) is outside of ERV3 and H-plk gene loci, Furthermore, we obtained evidence to define a critical region on chromosome 7 (7p12-7q11.23) that was frequently lost in surgically removed choriocarcinoma tissues and cell lines, Using a panel of microsatellite markers, biallelic deletions were observed, which strongly suggests the presence of a tumor suppressor gene(s) within this critical region. C1 KYUSHU UNIV,MED INST BIOREGULAT,DEPT REPROD PHYSIOL & ENDOCRINOL,BEPPU,OITA 874,JAPAN. TOTTORI UNIV,FAC MED,SCH LIFE SCI,DEPT MOL & CELL GENET,YONAGO,TOTTORI 683,JAPAN. ABBOTT LABS,DEPT CORP MOL BIOL,ABBOTT PK,IL 60064. NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. NR 59 TC 28 Z9 28 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 4 PY 1997 VL 15 IS 23 BP 2773 EP 2781 DI 10.1038/sj.onc.1201461 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YJ803 UT WOS:A1997YJ80300003 PM 9419968 ER PT J AU Bowen, R Glicklich, A Khan, M Rasmussen, S Wadden, T Bilstad, J Graham, D Green, L Lumpkin, M ONeill, R Sobel, S Hubbard, VS Yanovski, S Sopko, G AF Bowen, R Glicklich, A Khan, M Rasmussen, S Wadden, T Bilstad, J Graham, D Green, L Lumpkin, M ONeill, R Sobel, S Hubbard, VS Yanovski, S Sopko, G TI Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services interim public health recommendations, November 1997 (Reprinted from MMWR, vol 46, pg 1061-1066, 1997) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID DOPPLER C1 NIH,BETHESDA,MD 20892. CDC,DIV ADULT & COMMUNITY HLTH,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. CDC,DIV DIABET TRANSLAT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. CDC,DIV NUTR & PHYS ACT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. CDC,DIV ORAL HLTH,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. RP Bowen, R (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 9 TC 20 Z9 20 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 3 PY 1997 VL 278 IS 21 BP 1729 EP 1731 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YH987 UT WOS:A1997YH98700010 ER PT J AU Kaplan, JE Jaffe, HW Masur, H Holmes, KK AF Kaplan, JE Jaffe, HW Masur, H Holmes, KK TI Preventing opportunistic infections in HIV-infected injection drug users - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. RP Kaplan, JE (reprint author), CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333, USA. NR 6 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 DEC 3 PY 1997 VL 278 IS 21 BP 1743 EP 1744 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YH987 UT WOS:A1997YH98700024 ER PT J AU Lenfant, C AF Lenfant, C TI JNC guidelines - Is the message getting through? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Lenfant, C (reprint author), NHLBI,31 CTR DR,MSC 2486,BLDG 31,ROOM 5A52,BETHESDA,MD 20892, USA. NR 6 TC 13 Z9 13 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 DEC 3 PY 1997 VL 278 IS 21 BP 1778 EP 1779 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YH987 UT WOS:A1997YH98700035 PM 9388157 ER PT J AU Gordis, E AF Gordis, E TI Alcohol problems and public health policy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Gordis, E (reprint author), NIAAA,OFF DIRECTOR,MSC7003,SUITE 400,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 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 DEC 3 PY 1997 VL 278 IS 21 BP 1781 EP 1782 DI 10.1001/jama.278.21.1781 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YH987 UT WOS:A1997YH98700037 PM 9388159 ER PT J AU Cole, JW Hendler, RW Smith, PD Fredrickson, HA Pohida, TJ Friauf, WS AF Cole, JW Hendler, RW Smith, PD Fredrickson, HA Pohida, TJ Friauf, WS TI A high speed optical multichannel analyzer SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE optical multichannel analyzer; reaction mechanism; cytochrome oxidase; bacteriorhodopsin ID BACTERIORHODOPSIN AB An optical multichannel analyzer capable of recording spectra at sampling rates up to 100 kHz is described. The instrument, designed to gather data on the kinetic reaction mechanisms of biological preparations such as cytochrome oxidase and bacteriorhodopsin, features a massively parallel approach in which each photosensing element of the detector array has a dedicated amplifier, integrator, analog to digital converter, and sample buffer. The design has 92 such elements divided in two separate arrays, each of which sits at the focal plane of a 1/4 m Ebert spectrometer. The spectrometers may be tuned to cover independent, 130 nm wide, regions of the spectrum from 350 nm to 900 nm with a dispersion of 2.8 nm per clement. Each detection channel has 12-bit resolution with an electronic dark count of 1 count and may be sampled 1024 times during a single experiment with dynamically variable sampling intervals from 10 mu s to several seconds. Time averaging of up to thousands of consecutive laser-initiated kinetic cycles allows analyses of spectral changes <0.001 optical density units. A personal computer with custom software provides a number of features: entry of experiment parameters; transfer of data from temporary buffers to permanent files; real time display; multiple spectrum averaging; and control and synchronization of associated system hardware. Optical fibers or lenses provide coupling from a parabolic reflector Xenon are monitoring light source, through the sample chamber, to the entry slit of the monochromator. The instrument has been used for extensive studies on the rapid kinetics and definition of reaction sequences of the energy transducing enzymes cytochrome oxidase and bacteriorhodopsin. Some results from these studies are discussed. (C) 1997 Elsevier Science B.V. C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Cole, JW (reprint author), 9400 Wooden Bridge Rd, Potomac, MD 20854 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD DEC 3 PY 1997 VL 35 IS 3 BP 161 EP 174 DI 10.1016/S0165-022X(97)00037-7 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ202 UT WOS:000071360600003 PM 9470095 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Capillary electrophoresis of DNA fragments in 9 to 20% uncrosslinked polyacrylamide gels: unique separating capacity hypothetically related to maintenance of random-coil DNA conformation independently of gel concentration SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE uncrosslinked polyacrylamide; capillary electrophoresis; DNA fragments; separating capacity; DNA conformation ID INDUCED FLUORESCENCE DETECTION; LINEAR POLYACRYLAMIDE; MOBILITY DATA; OLIGONUCLEOTIDES; PRODUCTS AB DNA fragments (0.1 to 2 kb) were separated by capillary electrophoresis (CE) in 9 to 20% uncrosslinked polyacrylamide gels with a resolving power ranging from 3 to 0.1 million theoretical plates/meter across that DNA size range. The unique feature of electrophoresis in 18 to 20% uncrosslinked polyacryalmide is that it provides a method capable of resolving charge isomeric species of DNA fragments (0.4 to 2 kb), confirming a previous report by Heiger et al. [Heiger DN, Cohen AS, Karger BL. J Chromatogr 516 (1990) 33-48]. A similarly unique resolving capacity of uncrosslinked polyacrylamide gels for DNA previously reported is that for heteroduplex DNA [Pulyaeva H, Zakharov SF, Garner MM, Chrambach A. Electrophoresis 15 (1994) 1095-1100] matched by crosslinked gels only in the presence of denaturants [Peeters AV, Kotze MJ. PCR Methods Appl 4 (1994) 188-190; Ganguly A, Rock MJ, Prockop DJ. Proc Natl Acad Sci USA 90 (1993) 10 325-10 329], A clue as to the cause of that unique resolving capacity of uncrosslinked polyacrylamide is provided by the finding in the present study of a single, gel concentration independent K-R [retardation coefficient, d(log mobility)/d(gel concentration)] for the DNA fragments, which contrasts with the decrease of K-R with gel concentration observed for crosslinked polyacrylamide across a wide concentration range [Orban L, Chrambach A. Electrophoresis 12 (1991) 241-246; Tietz D, Chrambach A. Electrophoresis 14 (1993) 185-190]. Since the decrease of K-R with gel concentration correlates with a decrease in equivalent molecular radius [Tietz D, Chrambach A. Electrophoresis 14 (1993) 185-190], it has been interpreted as being due to the transition from a random-coiled to a stretched DNA conformation upon passage through gels of increasing concentration. Since in uncrosslinked gels the decrease of K-R does not occur, it is correspondingly assumed that the random-coil conformation of DNA is maintained in those gels in the investigated concentration range up to 20%. The maintenance of random-coil conformation would tend to enhance the resolving capacity of uncrosslinked polyacrylamide because size separation between DNA species is based on K-R differences that are maximal in that conformation [Tietz D, Chrambach A. Electrophoresis 14 (1993) 185-190]. The effect of denaturants in allowing for resolution of heteroduplex DNA in crosslinked gels [Peeters AV, Kotze MJ. PCR Methods Appl 4 (1994) 188-190; Ganguly A, Rock MJ, Prockop DJ, Proc Natl Acad Sci USA 90 (1993) 10 325-10 329] supports that hypothesis of the enhanced resolving power of electrophoresis in gels that maintain random-coiled DNA within the gel concentration range used. (C) 1997 Elsevier Science B.V. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 21 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD DEC 3 PY 1997 VL 35 IS 3 BP 175 EP 184 DI 10.1016/S0165-022X(97)00040-7 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ202 UT WOS:000071360600004 PM 9470096 ER PT J AU RodriguezBigas, MA Boland, CR Hamilton, SR Henson, DE Jass, JR Khan, PM Lynch, H Perucho, M Smyrk, T Sobin, L Srivastava, S AF RodriguezBigas, MA Boland, CR Hamilton, SR Henson, DE Jass, JR Khan, PM Lynch, H Perucho, M Smyrk, T Sobin, L Srivastava, S TI A National Cancer Institute workshop on hereditary nonpolyposis colorectal cancer syndrome: Meeting highlights and Bethesda guidelines SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MICROSATELLITE INSTABILITY; GENOMIC INSTABILITY; FAMILIES; MEMBERS; HISTORY; HNPCC; GENES; RISK C1 NCI,NIH,BETHESDA,MD 20892. ROSWELL PK CANC INST,BUFFALO,NY 14263. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. UNIV QUEENSLAND,SCH MED,BRISBANE,QLD,AUSTRALIA. LEIDEN UNIV,NL-2300 RA LEIDEN,NETHERLANDS. CREIGHTON UNIV,OMAHA,NE 68178. BURNHAM INST,LA JOLLA,CA 92037. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NR 25 TC 687 Z9 718 U1 1 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 3 PY 1997 VL 89 IS 23 BP 1758 EP 1762 DI 10.1093/jnci/89.23.1758 PG 5 WC Oncology SC Oncology GA YH759 UT WOS:A1997YH75900008 PM 9392616 ER PT J AU Tucker, MA Murray, N Shaw, EG Ettinger, DS Mabry, M Huber, MH Feld, R Shepherd, FA Johnson, DH Grant, SC Aisner, J Johnson, BE AF Tucker, MA Murray, N Shaw, EG Ettinger, DS Mabry, M Huber, MH Feld, R Shepherd, FA Johnson, DH Grant, SC Aisner, J Johnson, BE TI Second primary cancers related to smoking and treatment of small-cell lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; 2ND PRIMARY MALIGNANCIES; LONG-TERM SURVIVAL; HODGKINS-DISEASE; BREAST-CANCER; RISK; CHEMOTHERAPY; CARCINOMA; MORTALITY; TUMORS AB Background: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung, The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small, We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. Methods: Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated, Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths, The actuarial risk of second cancers was estimated by the Kaplan-Meier method, Results: Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold, Second lung cancer risk mas increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21), Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. Implications: Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention. C1 NCI,GENET EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. MAYO CLIN,ROCHESTER,MN. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. RHONE POULENC RORER,NORRISTOWN,PA. PRINCESS MARGARET HOSP,TORONTO,ON M4X 1K9,CANADA. TORONTO HOSP,TORONTO,ON,CANADA. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. INST CANC RES,NEW BRUNSWICK,NJ. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. RI Johnson, David/A-7437-2009; Tucker, Margaret/B-4297-2015 NR 28 TC 115 Z9 116 U1 1 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 DEC 3 PY 1997 VL 89 IS 23 BP 1782 EP 1788 DI 10.1093/jnci/89.23.1782 PG 7 WC Oncology SC Oncology GA YH759 UT WOS:A1997YH75900011 PM 9392619 ER PT J AU Tarone, RE Chu, KC AF Tarone, RE Chu, KC TI Recent trends in US breast cancer incidence, survival, and mortality rates - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BIRTH COHORT PATTERNS; UNITED-STATES; PHYSICAL-ACTIVITY C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NCI,OFF SPECIAL POPULAT RES,BETHESDA,MD 20892. NR 14 TC 4 Z9 4 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 3 PY 1997 VL 89 IS 23 BP 1811 EP 1812 PG 2 WC Oncology SC Oncology GA YH759 UT WOS:A1997YH75900016 ER PT J AU Butzow, JJ Garland, C VanLee, L Eichhorn, GL AF Butzow, JJ Garland, C VanLee, L Eichhorn, GL TI Specificity of an Escherichia coli RNA polymerase-associated NTPase SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE INCORPORATION; ACTIVE-SITE; PURIFICATION; DNA; TRANSCRIPTION; FIDELITY; ELONGATION; MECHANISM; ATPASE; ERRORS AB Standard preparations of Escherichia coli RNA polymerase harbor a 70 kDa protein with NTPase (beta-gamma cleavage) activity that is not a recognized polymerase subunit. The NTPase activity of this component, before and after separation from the polymerase, is strongly dependent on the presence of DNA; single-stranded polydeoxynucleotides are more effective than double-stranded. ATP and GTP are cleaved, the latter much less readily. The NTPase as I; occurs with the polymerase displays cleavage preference for NTPs that are not complementary to the DNA, a fact that has led to proposals for involvement of the NTPase in transcriptional error prevention [Volloch, V. Z., Rits, L. & Tumerman, L. (1979) Nucleic Acids Res, 6, 1535-1546; Libby, R. T., Nelson, J. LI, Calvo, J. M., & Gallant, J. A. (1989) EMBO J. 8, 3253-3158]. We find, however, that the lesser cleavage in the presence of complementary DNA results from competition for the NTP between the processes of incorporation by the polymerase and of cleavage by the NTPase, operating on the same substrate pool. The greater cleavage with noncomplementary DNA occurs because of the lack of incorporation by the polymerase, which then dots not compete with the NTPase for the substrate pool. Thus, these findings indicate that the cleavage preference of the NTPase for noncomplementary NTPs is not part of a mechanism for error prevention during transcription. RP Butzow, JJ (reprint author), NIA,GERONTOL RES CTR,NIH,BAYVIEW CAMPUS,BALTIMORE,MD 21224, USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 2 PY 1997 VL 36 IS 48 BP 14794 EP 14798 DI 10.1021/bi970191r PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YJ709 UT WOS:A1997YJ70900022 PM 9398200 ER PT J AU Agoston, GE Vaughan, R Lever, JR Izenwasser, S Terry, PD Newman, AH AF Agoston, GE Vaughan, R Lever, JR Izenwasser, S Terry, PD Newman, AH TI A novel photoaffinity label for the dopamine transporter based on N-substituted 3 alpha-[bis(4 '-fluorophenyl)methoxy]tropane SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID LIGAND-BINDING DOMAINS; UPTAKE INHIBITORS; COCAINE RECEPTOR; ANALOGS; RADIOSYNTHESIS; POTENT AB A novel photoaffinity label for the dopamine transporter (DAT) based on N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane has been synthesized in five steps and has been characterized. Preliminary binding studies indicated this ligand bound irreversibly to the dopamine transporter. Preparation of the I-125 analog and its photoactivation in the presence of membrane bound DAT demonstrated it covalently binds to the DAT. Published by Elsevier Science Ltd. C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Newman, AH (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Izenwasser, Sari/G-9193-2012 NR 13 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 2 PY 1997 VL 7 IS 23 BP 3027 EP 3032 DI 10.1016/S0960-894X(97)10139-1 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA YM283 UT WOS:000071048100021 ER PT J AU Libby, P Egan, D Skarlatos, S AF Libby, P Egan, D Skarlatos, S TI Roles of infectious agents in atherosclerosis and restenosis - An assessment of the evidence and need for future research SO CIRCULATION LA English DT Article DE endothelium; leukocytes; muscle, smooth; risk factors; viruses ID HERPES-SIMPLEX VIRUS; TUMOR-NECROSIS-FACTOR; CORONARY-ARTERY DISEASE; SMOOTH-MUSCLE CELLS; CHLAMYDIA-PNEUMONIAE INFECTION; INTERLEUKIN-1 GENE-EXPRESSION; ACUTE MYOCARDIAL-INFARCTION; VASCULAR ENDOTHELIAL-CELLS; CYTOMEGALOVIRUS-INFECTION; RISK FACTOR C1 NHLBI,NIH,BETHESDA,MD 20892. RP Libby, P (reprint author), HARVARD UNIV,DEPT MED,DIV CARDIOVASC,BRIGHAM & WOMENS HOSP,SCH MED,221 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 91 TC 392 Z9 408 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 2 PY 1997 VL 96 IS 11 BP 4095 EP 4103 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YG872 UT WOS:A1997YG87200038 PM 9403635 ER PT J AU Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK DiClemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A AF Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK DiClemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A TI Project MATCH secondary a priori hypotheses SO ADDICTION LA English DT Article ID INTERACTIONAL THERAPIES; COPING SKILLS; ALCOHOLICS; SCALE; RELIABILITY; DRINKING; SEVERITY AB Aims. (1) To assess the benefits of matching alcohol dependent clients to three treatments, based upon a priori hypotheses involving II client attributes; (2) to discuss the implications of these findings and of matching hypotheses previously reported from Project MATCH. Setting and participants. (1) Clients receiving outpatient therapy (N = 952; 72% male); (2) clients receiving aftercare therapy following inpatient or day hospital treatment (N= 774; 80% male). Intervention. Clients were randomly assigned to one of three 12-week, manual-guided, individual treatments: Cognitive Behavioral Coping Skills Therapy (CBT), Motivational Enhancement Therapy (MET) or Twelve-Step Facilitation Therapy (TSF). Design. Two parallel but independent randomized clinical trials were conducted, one with outpatients, one with aftercare clients. Participants were monitored over 15 months including a I-year post-treatment period. Individual differences in response to treatment were modeled as a latent growth process and evaluated for 17 contrasts specified a priori. Outcome measures were percentage of days abstinent and drinks per drinking day. Findings. Two a priori contrasts demonstrated significant post-treatment attribute by treatment interactions: (1) outpatients high in anger and treated in MET had better post-treatment drinking than in GBT; (2) aftercare clients high in alcohol dependence had better post-treatment outcomes in TSF; low dependence clients did better in CBT. Other matching effects varied over time, while still other interactions were opposite that predicted. Conclusions. (I) Anger and dependence should be considered when assigning clients to these three treatments; (2) considered together with the results of the primary hypotheses, matching effects contrasting these psychotherapies are not robust. Possible explanations include: (a) among the client variables and treatments tested, matching may not be an important factor in determining client outcomes; (b) design issues limited the robustness of effects; and (c) a more fully specified theory of matching is necessary to account for the complexity of the results. C1 NIAAA, Sci Commun Branch, Bethesda, MD 20892 USA. RP Allen, J (reprint author), NIAAA, Sci Commun Branch, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 51 TC 170 Z9 171 U1 1 U2 4 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1997 VL 92 IS 12 BP 1671 EP 1698 PG 28 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YL562 UT WOS:000070968600010 ER PT J AU Dawson, D AF Dawson, D TI Women and alcohol: contemporary and historical perspectives SO ADDICTION LA English DT Book Review C1 NIAAA, Rockville, MD 20852 USA. RP Dawson, D (reprint author), NIAAA, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1997 VL 92 IS 12 BP 1792 EP 1793 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YL562 UT WOS:000070968600023 ER PT J AU Sprott, R AF Sprott, R TI Grant application process in USA SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article C1 NIA, Biol Aging Program, NIH, Bethesda, MD 20892 USA. RP Sprott, R (reprint author), NIA, Biol Aging Program, NIH, Bldg 31, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD DEC PY 1997 VL 9 IS 6 BP 445 EP 446 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZA202 UT WOS:000072339200020 PM 9553635 ER PT J AU Rebok, GW Rasmusson, DX Bylsma, FW Brandt, J AF Rebok, GW Rasmusson, DX Bylsma, FW Brandt, J TI Memory improvement tapes: How effective for elderly adults? SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article ID MINI-MENTAL-STATE; CONTROL BELIEFS; TASKS; AGE AB The effectiveness of two commercially available audiocassette memory improvement programs was evaluated in a sample of 32 healthy, community-living elderly adults. Participants were given a set of either SyberVision's Neuropsychology of Memory Power tapes (Bornstein, 1989) or Nightingale-Conant's Mega Memory tapes (Trudeau, 1992), and a portable cassette player, and instructed to complete the programs within 10 weeks. All participants received a comprehensive battery of memory tests prior to and immediately following the memory improvement programs. Participants completing the memory improvement programs showed no greater gains in memory test performance than no-treatment control participants, but did report greater confidence in their memory abilities. Participants completing the Mega Memory program thought they were less likely to develop Alzheimer's disease after having completed it compared with participants in the other two conditions. Participants reported finding both tape programs acceptable and potentially useful for improving memory; those who completed the Memory Power program reported somewhat greater satisfaction than those completing the Mega Memory program. The claims about rapid, dramatic memory improvement with use of these products were not substantiated in this group of elderly adults and appear to be grossly exaggerated. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Johns Hopkins Res Ctr Fairhaven, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. RP Brandt, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Johns Hopkins Res Ctr Fairhaven, 600 N Wolfe St,Meyer 218, Baltimore, MD 21287 USA. OI Brandt, Jason/0000-0001-7381-6244 NR 29 TC 12 Z9 12 U1 2 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD DEC PY 1997 VL 4 IS 4 BP 304 EP 311 DI 10.1080/13825589708256655 PG 8 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA ZH625 UT WOS:000073130300006 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Screening, recruiting and predicting retention of participants in the NIMH Multisite HIV Prevention Trial SO AIDS LA English DT Article ID FOLLOW-UP; CLINICAL RESEARCH; ATTRITION; RECOMMENDATIONS; INTERVENTION; DIFFICULTY; DEPRESSION; TRACKING; PANEL; RISK C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 33 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S13 EP S19 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000002 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Methodological overview of the NIMH Multisite HIV Prevention Trial for populations at risk for HIV SO AIDS LA English DT Article ID AIDS-PREVENTION; CLINICAL-TRIALS; INTERVENTIONS; ADOLESCENTS; BEHAVIORS C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 19 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S1 EP S11 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000001 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Demographic and behavioral predictors of sexual risk in the NIMH Multisite HIV Prevention Trial SO AIDS LA English DT Article ID COCAINE USE; AIDS; HETEROSEXUALS; HISPANICS; PARTNERS; DRINKING; ADULTS; BLACK C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 25 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S21 EP S27 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000003 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Conceptual basis and procedures for the intervention in a multisite HIV prevention trial SO AIDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SELF-EFFICACY; UNITED-STATES; CONDOM-USE; SAFER SEX; BEHAVIORAL-CHANGE; AIDS RISK; EDUCATION; GENDER; WOMEN C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 49 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S29 EP S35 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000004 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Endpoints and other measures in the NIMH Multisite HIV Prevention Trial: rationale and psychometric properties SO AIDS LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; RISK-FACTORS; HETEROSEXUAL COUPLES; HOMOSEXUAL MEN; RELIABILITY; HISTORIES; TRANSMISSION; AGREEMENT; PARTNER C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 29 TC 1 Z9 1 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S37 EP S47 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000005 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Quality control and quality assurance in HIV prevention research: model from a multisite HIV prevention trial SO AIDS LA English DT Article ID PSYCHOTHERAPY; DEPRESSION C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S49 EP S53 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000006 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Collecting sexually transmitted disease clinic chart data in multisite studies SO AIDS LA English DT Article C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S59 EP S63 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000008 ER PT J AU Fishbein, M Coutinho, R AF Fishbein, M Coutinho, R CA NIMH Multisite HIV Prevention Trial TI Definition of adverse reactions in clinical trials of a behavioral intervention SO AIDS LA English DT Article C1 NIMH, Rockville, MD 20857 USA. RP Fishbein, M (reprint author), NIMH, Rockville, MD 20857 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1997 VL 11 SU 2 BP S55 EP S57 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YW329 UT WOS:000071923000007 ER PT J AU Helm, BA Spivey, AC Padlan, EA AF Helm, BA Spivey, AC Padlan, EA TI Peptide blocking of IgE/receptor interaction: possibilities and pitfalls SO ALLERGY LA English DT Review ID HIGH-AFFINITY RECEPTOR; FC-EPSILON-RI; HUMAN-IMMUNOGLOBULIN-E; STRUCTURE-BASED DESIGN; HUMAN IGE; ALPHA-SUBUNIT; BINDING-SITE; COMBINATORIAL TECHNOLOGIES; CYCLIC-PEPTIDES; PROTEIN HORMONE C1 Univ Sheffield, Krebs Inst Biomolec Res, Dept Mol Biol & Biotechnol, Sheffield S10 2UH, S Yorkshire, England. Univ Sheffield, Krebs Inst Biomolec Res, Dept Chem, Sheffield S10 2UH, S Yorkshire, England. NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Helm, BA (reprint author), Univ Sheffield, Krebs Inst Biomolec Res, Dept Mol Biol & Biotechnol, Sheffield S10 2UH, S Yorkshire, England. NR 101 TC 30 Z9 30 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD DEC PY 1997 VL 52 IS 12 BP 1155 EP 1169 DI 10.1111/j.1398-9995.1997.tb02518.x PG 15 WC Allergy; Immunology SC Allergy; Immunology GA YN315 UT WOS:000071154600001 PM 9450133 ER PT J AU Stone, PH Chaitman, BR Forman, S Andrews, TC Bittner, V Bourassa, MG Davies, RF Deanfield, JE Frishman, W Goldberg, AD MacCallum, G Ouyang, P Pepine, CJ Pratt, CM Sharaf, B Steingart, R Knatterud, GL Sopko, G Conti, CR AF Stone, PH Chaitman, BR Forman, S Andrews, TC Bittner, V Bourassa, MG Davies, RF Deanfield, JE Frishman, W Goldberg, AD MacCallum, G Ouyang, P Pepine, CJ Pratt, CM Sharaf, B Steingart, R Knatterud, GL Sopko, G Conti, CR TI Prognostic significance of myocardial ischemia detected by ambulatory electrocardiography, exercise treadmill testing, and electrocardiogram at rest to predict cardiac events by one year (The Asymptomatic Cardiac Ischemia Pilot [ACIP] Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; STABLE ANGINA; SILENT ISCHEMIA; DAILY-LIFE; INFARCTION; NIFEDIPINE; DILTIAZEM; EPISODES; ATENOLOL; THERAPY AB Myocardial ischemia identified by ambulatory electrocardiography (AECG), exercising treadmill testing, (ETT), or 12-lead electrocardiogram at rest is associated with an adverse prognosis, but the effect of improving these ischemic manifestations by treatment on outcome is unknown. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was a National Heart, lung, and Blood institute funded study to determine the feasibility of conducting a large-scale prognosis study and to assess the effect of 3 treatment strategies (angina-guided strategy, AECG ischemia-guided strategy, and revascularization strategy) in reducing the manifestations of ischemia as indicated by AECG and ETT. The study cohort for this database study consisted of 496 randomized patients who performed the AECG, ETT, and 12-lead electrocardiogram at rest at both the qualifying and week 12 visits. The effect of modifying ischemia by treatment on the incidence of cardiac events (death, myocardial infarction, coronary revascularization procedure, or hospitalization for an ischemic event) at 1 year was examined. In the 2 medical treatment groups (n = 328) there was an association between the number of ambulatory electrocardiographic ischemic episodes at the qualifying visit and combined cardiac events at 1 year (p = 0.003). In the AECG ischemia-guided patients there was a trend associating greater reduction in the number of ambulatory electrocardiographic ischemia episodes with a reduced incidence of combined cardiac events (r = -0.15, p = 0.06). In the revascularization strategy patients this association was absent. In the medical treatment patients the exercise duration on the baseline ETT was inversely associated with an adverse prognosis (p = 0.02). The medical treatment strategies only slightly improved the exercise time and the exercise duration remained of prognostic significance. In the revascularization group strategy patients this association was absent. Thus, myocardial ischemia detected by AECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically. (C) 1997 by Excerpta Medica, Inc. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV ALABAMA,BIRMINGHAM,AL. MONTEFIORE HOSP & MED CTR,ALBERT EINSTEIN COLL MED HOSP,BRONX,NY 10461. HENRY FORD HOSP,DETROIT,MI 48202. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. UNIV FLORIDA,GAINESVILLE,FL. BAYLOR COLL MED,HOUSTON,TX 77030. RHODE ISL HOSP,PROVIDENCE,RI. WINTHROP UNIV HOSP,MINEOLA HOSP,MINEOLA,NY. NHLBI,BETHESDA,MD 20892. MONTREAL HEART INST,RES CTR,MONTREAL,PQ H1T 1C8,CANADA. UNIV OTTAWA,INST HEART,OTTAWA,ON,CANADA. ST BARTHOLOMEWS HOSP,LONDON,ENGLAND. RP Stone, PH (reprint author), MARYLAND MED RES INST,ACIP CLIN COORDINATING CTR,BALTIMORE,MD 21210, USA. RI Deanfield, John/C-5178-2008; OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HV-90-07, HV-90-08, HV91-05] NR 26 TC 34 Z9 36 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1997 VL 80 IS 11 BP 1395 EP 1401 DI 10.1016/S0002-9149(97)00706-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YJ524 UT WOS:A1997YJ52400001 PM 9399710 ER PT J AU Laurienzo, JM Cannon, RO Quyyumi, A Dilsizian, V Panza, JA AF Laurienzo, JM Cannon, RO Quyyumi, A Dilsizian, V Panza, JA TI Improved specificity of transesophageal dobutamine stress echocardiography compared to standard tests for evaluation of coronary artery disease in women presenting with chest pain SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL PERFUSION SCINTIGRAPHY; DIPYRIDAMOLE-ECHOCARDIOGRAPHY; EXERCISE-ELECTROCARDIOGRAPHY; ARTERIOGRAPHY; THALLIUM; ACCURACY AB The detection of coronary artery disease (CAD) by noninvasive methods has been hindered in women by the high rate of false-positive results, To determine the feasibility and accuracy of transesophageal dobutamine stress echocardiography for identification of CAD in women, we studied 84 patients (age 51 +/- 11 years) who underwent symptom-limited exercise treadmill testing, exercise thallium-201 scintigraphy, and coronary angiography for evaluation of anginal chest pain. OF the 84 patients, 62 had normal coronary arteries or nonsignificant coronary lesions, and 22 had significant stenosis of greater than or equal to 1 major coronary artery. During treadmill exercise, repolarization changes were observed in 16 of 21 patients with CAD and in 19 of 60 patients with normal coronary arteries. With thallium scintigraphy, a reversible defect was observed in 19 of 22 patients with CAD and in 12 of 60 patients with normal coronary arteries. Regional wall motion abnormalities during dobutamine infusion developed in 18 of 22 patients with CAD and in none of the 62 patients with normal coronary arteries, All 3 tests had similar sensitivity for detection of CAD (76% for exercise treadmill test, 86% for thallium scintigraphy, and 82% for transesophageal dobutamine stress echocardiography). However, transesophageal dobutamine stress echocardiography had significantly higher specificity than the other 2 tests (100% vs 68% for exercise treadmill test and 80% for thallium scintigraphy; p = 0.0001). Thus, transesophageal dobutamine stress echocardiography is accurate for evaluation of CAD among women presenting with chest pain; its use should be considered when more conventional tests are equivocal or technically suboptimal. (C) 1997 by Excerpta Medica, Inc. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 30 TC 14 Z9 14 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1997 VL 80 IS 11 BP 1402 EP 1407 DI 10.1016/S0002-9149(97)00702-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YJ524 UT WOS:A1997YJ52400002 PM 9399711 ER PT J AU Koh, KK Bui, MN Mincemoyer, R Cannon, RO AF Koh, KK Bui, MN Mincemoyer, R Cannon, RO TI Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; E-SELECTIN; HUMAN ATHEROSCLEROSIS; CIRCULATING ICAM-1; CULTURED HUMAN; HEART-DISEASE; EXPRESSION; VCAM-1; SERUM C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. INHA UNIV,DEPT INTERNAL MED,SUNGNAM SI,SOUTH KOREA. NR 20 TC 77 Z9 79 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1997 VL 80 IS 11 BP 1505 EP 1507 DI 10.1016/S0002-9149(97)00732-7 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YJ524 UT WOS:A1997YJ52400028 PM 9399737 ER PT J AU Warnecke, RB Sudman, S Johnson, TP ORourke, D Davis, AM Jobe, JB AF Warnecke, RB Sudman, S Johnson, TP ORourke, D Davis, AM Jobe, JB TI Cognitive aspects of recalling and reporting health-related events: Papanicolaou smears, clinical breast examinations, and mammograms SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE mammography; Papanicolaou smear; questionnaires; retrospective studies ID BEHAVIORAL FREQUENCY QUESTIONS; MEDICAL RECORD; PAP SMEAR; SELF-REPORTS; CANCER; CARE; ACCURACY; AGREEMENT; MEMORY AB This paper reports an examination of cognitive processes used by 178 women aged 50 years and older in retrieving information about the frequency with which they received Papanicolaou smears, mammograms, and clinical breast examinations, Women were selected from a health maintenance organization in which they had been enrolled for at least 51/2 years, The literature suggested that reporting of regular events such as these kinds of tests is likely to be based on schemas, which is an estimation technique in which events are reported in a format with generic content, Thus, if the procedure is believed to occur annually, the respondent will report receiving five tests in 5 years, The study attempted to evaluate whether use of episodic recall, in which respondents are forced to report individual events, would be more accurate than reports based on estimation using a schema format, The results indicated that most of the errors occurred in Papanicolaou smear reporting, which is consistent with the literature, and that the fewest errors occurred with mammograms. Regardless of the questionnaire format, respondents persisted in using schemas based on the date of annual physical examination, Most reporting errors occurred because the interval between examinations was estimated incorrectly. C1 UNIV ILLINOIS, COLL COMMERCE, URBANA, IL 61801 USA. RUSH, ANCHOR HLTH MAINTENANCE ORG, CHICAGO, IL USA. NIA, DEPT HLTH & HUMAN SERV, NIH, BETHESDA, MD 20892 USA. RP Warnecke, RB (reprint author), UNIV ILLINOIS, SURVEY RES LAB,COLL URBAN PLANNING & PUBL AFFAIRS, 910 W VAN BUREN,SUITE 500, MC 336, CHICAGO, IL 60607 USA. FU PHS HHS [200-91-7035] NR 48 TC 74 Z9 74 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1997 VL 146 IS 11 BP 982 EP 992 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YJ904 UT WOS:A1997YJ90400013 PM 9400341 ER PT J AU Goedert, JJ Erdman, DD Konkle, BA Torok, TJ Lederman, MM Kleinert, D Mandalaki, T Kessler, CM Anderson, LJ Luban, NLC AF Goedert, JJ Erdman, DD Konkle, BA Torok, TJ Lederman, MM Kleinert, D Mandalaki, T Kessler, CM Anderson, LJ Luban, NLC TI Parvovirus B19 quiescence during the course of human immunodeficiency virus infection in persons with hemophilia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE parvovirus B19; human immunodeficiency virus; AIDS; hemophilia; polymerase chain reaction; prospective cohort study ID PCR AMPLIFICATION; AIDS; HIV; DNA AB To detect and characterize parvovirus B19 infection during the course of progressive immune deficiency from human immunodeficiency virus (HIV), ten subjects enrolled in the Multicenter Hemophilia Cohort Study were followed for 6.4 to 15 years from HIV seroconversion through extreme immune deficiency. Four to five sera or plasma samples from each subject, collected at predetermined CD4(+) lymphocyte levels, were tested for immunoglobulin G (IgG) and M (IgM) B19 antibodies and DNA, All 42 samples were positive for B19 IgG antibodies, and three were weakly positive for IgM antibodies, Only one sample, collected coincident with HIV seroconversion, was unequivocally positive for B19 DNA, No persistent hematologic adverse effects of B19 infection were observed, Thus, although B19 IgG antibodies are highly prevalent among HIV-infected persons with hemophilia or related disorders, B19 viremia and its hematologic consequences were not detected, even with severe depletion of CD4(+) lymphocytes. if primary B19 infection occurs after immune deficiency, however, the consequences may be more adverse. (C) 1997 Wiley-Liss, Inc. C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. CTR DIS CONTROL & PREVENT,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA. THOMAS JEFFERSON UNIV,CARDEZA FDN HEMOPHILIA CTR,PHILADELPHIA,PA. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. UNIV ATHENS,LAIKON HOSP,ATHENS,GREECE. GEORGE WASHINGTON UNIV HOSP,WASHINGTON,DC. CHILDRENS HOSP NATL MED CTR,WASHINGTON,DC. FU NCI NIH HHS [N01-CP-33002, N01-CP-33060] NR 16 TC 6 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 1997 VL 56 IS 4 BP 248 EP 251 PG 4 WC Hematology SC Hematology GA YJ514 UT WOS:A1997YJ51400009 PM 9395187 ER PT J AU Carrington, M Kissner, T Gerrard, B Ivanov, S O'Brien, SJ Dean, M AF Carrington, M Kissner, T Gerrard, B Ivanov, S O'Brien, SJ Dean, M TI Novel alleles of the chemokine-receptor gene CCR5 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HIV-1 INFECTION; FUNCTIONAL EXPRESSION; DISEASE PROGRESSION; MIP-1-ALPHA; INDIVIDUALS; MIP-1-BETA; RESISTANCE; PHENOTYPE; COFACTOR; CLONING AB The CCR5 gene encodes a cell-surface chemokine-receptor molecule that serves as a coreceptor for macrophage-tropic strains of HIV-1. Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding/signaling or HIV-1 infection of cells that normally express CCR5 protein. Indeed, homozygotes for a 32-bp deletion allele of CCR5 (CCR5-Delta 32), which causes a frameshift at amino acid 185, are relatively resistant to HIV-1 infection. Here we report the identification of 16 additional mutations in the coding region of the CCR5 gene, all but 3 of which are codon altering or "nonsynonymous." Most mutations were rare (found only once or twice in the sample); five were detected exclusively among African Americans, whereas eight were observed only in Caucasians. The mutations included 11 codon-altering nonsynonymous variants, one trinucleotide deletion, one chain-termination mutant, and three synonymous mutations. The high predominance of codon-altering alleles among CCR5 mutants (14/17 [81%], including CCR5-Delta 32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures. C1 Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Carrington, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 28 TC 117 Z9 119 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1997 VL 61 IS 6 BP 1261 EP 1267 DI 10.1086/301645 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YT019 UT WOS:000071555900008 PM 9399903 ER PT J AU DeVoto, E Fiore, BJ Millikan, R Anderson, HA Sheldon, L Sonzogni, WC Longnecker, MP AF DeVoto, E Fiore, BJ Millikan, R Anderson, HA Sheldon, L Sonzogni, WC Longnecker, MP TI Correlations among human blood levels of specific PCB congeners and implications for epidemiologic studies SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE polychlorinated biphenyls; environmental exposure; epidemiology; dietary exposure ID POLYCHLORINATED-BIPHENYLS; HUMAN-MILK; EXPOSURE; DIOXINS; WOMEN AB Specific congeners of PCBs may differ with respect to their human health risks. For epidemiologic studies, however, measuring levels of specific congeners-as compared with estimating the concentration of total PCBs present, may be of limited value if levels of specific congeners are highly correlated. We examined the correlations among levels of specific congeners in three groups: controls from a case-control study of breast cancer in North Carolina and two groups from Wisconsin with exposure to fish from contaminated waters. Levels of specific congener were, in general, highly correlated (Pearson r > 0.80). However, the level of congener 180, a heptachlorobiphenyl, tended to be less correlated with levels of lower-chlorinated biphenyls. Among the implications of these findings are that measurement of a select group of congeners may yield essentially the same information as measurement of a large panel, and may be more cost efficient. (C) 1997 Wiley-Liss, Inc. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. DEPT HLTH & FAMILY SERV,DIV HLTH,BUR PUBL HLTH,MADISON,WI. RES TRIANGLE INST,ANALYT & CHEM SCI UNIT,RES TRIANGLE PK,NC 27709. UNIV WISCONSIN,HYG LAB,MADISON,WI. OI Longnecker, Matthew/0000-0001-6073-5322 FU NIEHS NIH HHS [R01-ES07 128] NR 22 TC 51 Z9 51 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1997 VL 32 IS 6 BP 606 EP 613 DI 10.1002/(SICI)1097-0274(199712)32:6<606::AID-AJIM6>3.0.CO;2-N PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YE138 UT WOS:A1997YE13800006 PM 9358917 ER PT J AU Sata, F Araki, S Sakai, T Nakata, A Yamashita, K Morita, Y Tanigawa, T Miki, A AF Sata, F Araki, S Sakai, T Nakata, A Yamashita, K Morita, Y Tanigawa, T Miki, A TI Immunological effects of CaEDTA injection: Observations in two lead workers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE lead; calcium disodium ethylenediamine tetraacetate (CaEDTA); immunoglobulin; lymphocyte; immune system ID CELLULAR IMMUNE FUNCTION; CYTO-TOXICITY; EXPOSURE; IMMUNOGLOBULIN; LYMPHOCYTES; PLASMA; CELLS AB To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) injection on human immune system in relation to exposure to lend, we administered CaEDTA by intravenous injection for 1 hr three times (three consecutive days) a week to two male lead workers. They had been engaged in recycling lend for 31 and 22 years, aged 61 and 53 years (workers 1 and 2), respectively Before the treatment of CaEDTA, their blood lend concentrations (PbB) were 81 and 68 mu g/dl, respectively, The administration of CaEDTA had been carried out to worker 1 for 10 weeks and to worker 2 for 6 weeks. A significant decrease in PbB between before and after three-times CaEDTA injection was found in both workers. Significant increases in IgG, IgA, IgM, CD8+, and CD57+ cells were found in worker I,A significant increase in IgD was found in worker 2. During the study period IgG in worker 1 and CD4+ cells in worker 2 were gradually increasing. There was significant negative correlation between IgG and PbB in worker 1. It is suggested that the immunological function such ns antibody formation in lend workers might be improved by CaEDTA injection. (C) 1997 Wiley-Liss, Inc. C1 UNIV TOKYO,FAC MED,DEPT PUBL HLTH,BUNKYO KU,TOKYO 113,JAPAN. UNIV TOKYO,GRAD SCH MED,DEPT MENTAL HLTH,TOKYO,JAPAN. NCI,NIH,BETHESDA,MD 20892. TOKYO LABOR ACCIDENT HOSP,CTR OCCUPAT MED,TOKYO,JAPAN. NATL INST IND HLTH,KAWASAKI,KANAGAWA,JAPAN. UNIV TSUKUBA,INST COMMUNITY MED,TSUKUBA,IBARAKI 305,JAPAN. RI Nakata, Akinori/A-2399-2008 NR 26 TC 2 Z9 2 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1997 VL 32 IS 6 BP 674 EP 680 DI 10.1002/(SICI)1097-0274(199712)32:6<674::AID-AJIM15>3.0.CO;2-Z PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YE138 UT WOS:A1997YE13800015 PM 9358926 ER PT J AU Pham, PT Lew, SQ Balow, JE AF Pham, PT Lew, SQ Balow, JE TI Sickle cell nephropathy during the postpartum period in a patient with SLE SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article ID RISK-FACTORS; DISEASE; GLOMERULOPATHY; MORTALITY; ANEMIA C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,DIV RENAL DIS & HYPERTENS,WASHINGTON,DC 20037. NIH,KIDNEY DIS SECT,BETHESDA,MD 20892. NR 21 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1997 VL 30 IS 6 BP 879 EP 883 DI 10.1016/S0272-6386(97)90099-8 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YK714 UT WOS:A1997YK71400025 PM 9398137 ER PT J AU Xiao, GH Jin, F KleinSzanto, AJP Goodrow, TL Linehan, MW Yeung, RS AF Xiao, GH Jin, F KleinSzanto, AJP Goodrow, TL Linehan, MW Yeung, RS TI The FHIT gene product is highly expressed in the cytoplasm of renal tubular epithelium and is down-regulated in kidney cancers SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR; CELL CARCINOMAS; 3P14.2; HEAD AB Loss of heterozygosity and homozygous deletion of the 3p14.2 region in human cancers implies the existence of a tumor suppressor gene. One such candidate is the fragile histidine triad (FHIT) gene. To investigate the role of FHIT gene product in tumorigenesis, we generated specific polyclonal antibodies to the human protein and studied its expression in normal and tumor tissues. Immunoblot analysis revealed highly variable expression of pFhit in normal adult human tissues. The highest steady-state level of pFhit was found in kidney and brain, whereas breast, intestine, and skeletal muscle expressed only trace amounts, Within the kidney, the pattern of pFhit immunoreactivity was confined to the tubular epithelium and absent in the glomeruli, Immunofluorescence analysis and biochemical fractionation have sublocalized pFhit to the cytosolic compartment, Compared with normal kidney, pFhit was found to be down-regulated in a subset of primary renal cell carcinoma. Two of 12 renal cell carcinoma cell lines that are known not to contain VHL mutations showed complete loss of pFhit expression. This is supported by the appearance of aberrant reverse transcription-polymerase chain reaction products and loss of the normal-size fragment. Our results are consistent with a potential role of pFhit loss or dysfunction in human renal cell carcinoma independent of VHL involvement. C1 FOX CHASE CANC CTR,DIV MED SCI,PHILADELPHIA,PA 19111. NIH,DIV UROL ONCOL,BETHESDA,MD 20892. RI Klein-Szanto, Andres/E-6218-2010 FU NCI NIH HHS [CA06927, CA61889] NR 15 TC 31 Z9 38 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1997 VL 151 IS 6 BP 1541 EP 1547 PG 7 WC Pathology SC Pathology GA YK712 UT WOS:A1997YK71200007 PM 9403704 ER PT J AU Riminucci, M Fisher, LW Shenker, A Spiegel, AM Bianco, P Robey, PG AF Riminucci, M Fisher, LW Shenker, A Spiegel, AM Bianco, P Robey, PG TI Fibrous dysplasia of bone in the McCune-Albright syndrome - Abnormalities in bone formation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID STIMULATORY G-PROTEIN; ACTIVATING MUTATIONS; ALKALINE-PHOSPHATASE; SIALOPROTEIN BSP; ALPHA-SUBUNIT; CELLS-INVITRO; EXPRESSION; TISSUES; LOCALIZATION; OSTEOPONTIN AB In addition to cafe-au-lait pigmentation patterns and hyperendocrinopathies, fibrous dysplasia of bone is a major finding in the McCune-Albright syndrome, Activating missense mutations of the Gs alpha gene leading to overactivity of adenylyl cyclase have been identified in patients with McCune-Albright syndrome, but the mechanism leading to the specific development of fibrous dysplasia in bone has not been elucidated, By means of specific peptide antisera and reverse transcriptase polymerase chain reaction in situ hybridization, we show that expression of Gs alpha and its mRNA is critically up-regulated during maturation of precursor osteogenic cells to normal osteoblast cells and that this pattern of expression is retained in fibrous dysplasia, A functional characterization of fibrous dysplastic tissues revealed that the fibrotic areas consist, in fact, of an excess of cells with phenotypic features of pre-osteogenic cells, whereas the lesional bone formed de novo within fibrotic areas represents the biosynthetic output of mature but abnormal osteoblasts. These cells are noted for peculiar changes in cell shape and interaction with matrix, which were mimicked in vitro by the effects of excess exogenous cAMP on human osteogenic cells, Osteoblasts involved with the de novo deposition of lesional bone in fibrous dysplasia produce a bone matrix enriched in certain anti-adhesion molecules (versican and osteonectin), and poor in the pro-adhesive molecules osteopontin and bone sialoprotein, which is in contrast to the high levels of these two proteins found in normal de novo bone, Our data indicate the need to reinterpret fibrous dysplasia of bone as a disease of cells in the osteogenic Lineage, related to the effects of excess cAMP on bone cell function. They further suggest that a critical, physiological, maturation-related regulation of Gs alpha levels makes cells in the osteogenic lineage a natural target for the effects of mutations Ln the Gs alpha gene and may provide a clue as to why bone itself is affected in this somatic, mutation-dependent disease. C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DEPT EXPT MED,I-00185 ROME,ITALY. UNIV AQUILA,DEPT EXPT MED,DIV PATHOL,I-67100 LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.0519] NR 35 TC 131 Z9 134 U1 1 U2 2 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 DEC PY 1997 VL 151 IS 6 BP 1587 EP 1600 PG 14 WC Pathology SC Pathology GA YK712 UT WOS:A1997YK71200013 PM 9403710 ER PT J AU Henske, EP Wessner, LL Golden, J Scheithauer, BW Vortmeyer, AO Zhuang, ZP KleinSzanto, AJP Kwiatkowski, DJ Yeung, RS AF Henske, EP Wessner, LL Golden, J Scheithauer, BW Vortmeyer, AO Zhuang, ZP KleinSzanto, AJP Kwiatkowski, DJ Yeung, RS TI Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUBEROUS-SCLEROSIS-2 TSC2 GENE; NERVOUS-SYSTEM LESIONS; EKER RAT MODEL; GROWTH SUPPRESSOR; ALLELIC LOSS; HETEROZYGOSITY; HAMARTOMAS; PROTEIN; REGION; HYDROCEPHALUS AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and tumors of skin, brain, heart, and kidney, In this study, we focused on two of the most frequent tumors in TSC patients, renal angiomyolipomas and subependymal giant cell astrocytomas (SEGAs), Two questions were addressed. First, is loss of tuberin, the product of the TSC2 gene, seen in both renal and central nervous system tumors from TSC patients? Second, when loss of tuberin occurs, does it affect each of the cell types seen in these tumors? We used a loss of heterozygosity approach to identify tumors from TSC2 patients, We found loss of tuberin immunostaining in the spindle and epithelioid cells but not in the giant cells of six TSC2 SEGAs, We also found loss of tuberin immunostaining in all three cell types (smooth muscle, fat, and vessels) of six TSC2 angiomyolipomas. Chromosome 16p13 loss of heterozygosity occurred in both spindle and epithelioid cells of a SEGA and in smooth muscle and fat but not the vessels of two angiomyolipomas, These results support a two-hit tumor suppressor model for the pathogenesis of SEGAs and angiomyolipomas. The vascular elements of angiomyolipomas and the giant cells of SEGAs may be reactive rather than neoplastic. C1 FOX CHASE CANC CTR, DEPT PATHOL, PHILADELPHIA, PA 19111 USA. FOX CHASE CANC CTR, DEPT SURG ONCOL, PHILADELPHIA, PA 19111 USA. CHILDRENS HOSP PHILADELPHIA, DEPT NEUROPATHOL, PHILADELPHIA, PA 19104 USA. MAYO CLIN, DEPT PATHOL, ROCHESTER, MN USA. NCI, DEPT PATHOL, BETHESDA, MD 20892 USA. BRIGHAM & WOMENS HOSP, DIV EXPT MED, BOSTON, MA 02115 USA. RP Henske, EP (reprint author), FOX CHASE CANC CTR, DEPT MED ONCOL, 7701 BURHOLME AVE, PHILADELPHIA, PA 19111 USA. RI Klein-Szanto, Andres/E-6218-2010 FU NCI NIH HHS [CA61889] NR 43 TC 103 Z9 107 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1997 VL 151 IS 6 BP 1639 EP 1647 PG 9 WC Pathology SC Pathology GA YK712 UT WOS:A1997YK71200017 PM 9403714 ER PT J AU Lietard, J Musso, O Theret, N LHelgoualch, A Campion, JP Yamada, Y Clement, B AF Lietard, J Musso, O Theret, N LHelgoualch, A Campion, JP Yamada, Y Clement, B TI Sp1-mediated transactivation of LamC1 promoter and coordinated expression of laminin-gamma 1 and Sp1 in human hepatocellular carcinomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRANSCRIPTION FACTOR SP1; ADULT-RAT HEPATOCYTES; C-MYC PROMOTER; DIFFERENTIAL EXPRESSION; BINDING PROTEINS; RIBONUCLEIC-ACID; RECEPTOR LBP-32; LAMININ CHAINS; HEPATOMA-CELLS; COLLAGEN GENE AB The laminin-gamma 1 chain is present in most basement membranes and is involved in various physiological and pathological processes, including carcinogenesis in the liver. We have investigated the role of the transcription factor Sp1 in the activation of the LamC1 gene, which encodes laminin-gamma 1, both in hepatocytes and in human hepatocellular carcinomas. DNAse I hypersensitive sites were mapped in the murine LamC1 promoter using early hepatocyte primary cultures in which LamC1 becomes activated, Three hypersensitive sites were found in enhancer-like elements that contain GC-rich regions. Gel-shift analyses showed that specific complexes were resolved using GC-containing oligonucleotides and Faza 567 hepatoma cells, which constitutively express laminin-gamma 1 at a high level. Increased GC-binding activity was observed using nuclear extracts from early hepatocyte cultures versus normal liver. Sp1 overexpression in normal hepatocytes transfected with an Sp1 expression vector induced a marked increased of laminin-gamma 1 mRNA content and co-transfection of promoter fragments in Drosophila melanogaster SL2 cells demonstrated that Spl transactivates LamC1. In human hepatocellular carcinomas, Sp1 and laminin-gamma 1 mRNA were simultaneously expressed at high levels, and gel-shift experiments demonstrated a higher GC-binding activity to Sp1 compared with control Livers. In situ hybridization indicated that cells exhibiting a high content of laminin-gamma 1 mRNA were also strongly positive for Sp1 mRNA, including both cancer cells at the invasion front and stromal cells. These results show that Sp1 is involved in the activation of LamC1 that occurs in human hepatocellular carcinomas. C1 UNIV RENNES 1,FAC MED & PHARM,INSERM,U456,DETOXICAT & TISSUE REPAIR UNIT,F-35043 RENNES,FRANCE. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. RI Theret, Nathalie/I-2871-2015; Clement, Bruno/E-5546-2016 NR 53 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1997 VL 151 IS 6 BP 1663 EP 1672 PG 10 WC Pathology SC Pathology GA YK712 UT WOS:A1997YK71200020 PM 9403717 ER PT J AU Sallinen, SL Sallinen, P Haapasalo, H Kononen, J Karhu, R Helen, P Isola, J AF Sallinen, SL Sallinen, P Haapasalo, H Kononen, J Karhu, R Helen, P Isola, J TI Accumulation of genetic changes is associated with poor prognosis in grade II astrocytomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SEQUENCE COPY NUMBER; SOLID TUMORS; GLIOMA; SURVIVAL; SAMPLES; ADULTS AB Unexpectedly aggressive clinical course of some grade II astrocytomas is a diagnostic dilemma for routine histopathology. Because increasing tumor malignancy is a consequence of progressive accumulation of chromosomal alterations, we investigated whether aggressive behavior of grade II astrocytomas could be predicted by the number and type of gross chromosomal aberrations. We used comparative genomic hybridization to analyze 11 grade II astrocytomas with typical (good, n = 7) or poor (n = 4) prognosis. The results were also compared with a reference material of 13 grade III-IV astrocytomas and nine established cell lines. We found a median of two aberrations (range 0 to 4) in tumors with good prognosis and of 15.5 changes (range 8 to 28) in tumors with poor prognosis. Chromosomal gains were present in both groups, whereas chromosomal losses were frequent in tumors with poor prognosis (median 9.5, range 3 to 14) but rare in tumors with good prognosis (range 0 to 2). All chromosomal gains were also found in the high-grade astrocytoma group and the majority of them in cell lines. Chromosomal losses in grade II astrocytomas with poor prognosis were very similar to those in grade III-IV astrocytomas and cell lines. We conclude that an early accumulation of genetic changes in grade II astrocytomas is closely associated with poor patient prognosis, suggesting diagnostic use for comparative genomic hybridization in characterization of grade n astrocytomas. C1 UNIV TAMPERE,TAMPERE UNIV HOSP,DEPT PATHOL,FIN-33101 TAMPERE,FINLAND. UNIV TAMPERE,TAMPERE UNIV HOSP,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 27 TC 35 Z9 36 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 DEC PY 1997 VL 151 IS 6 BP 1799 EP 1807 PG 9 WC Pathology SC Pathology GA YK712 UT WOS:A1997YK71200034 PM 9403731 ER PT J AU Meehan, S Wu, AJ Kang, EC Sakai, T Ambudkar, IS AF Meehan, S Wu, AJ Kang, EC Sakai, T Ambudkar, IS TI Interferon-gamma induces a decrease in the intracellular calcium pump in a human salivary gland cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE sarco(endo)plasmic reticulum calcium adenosinetriphosphatase protein; intracellular calcium ion store; salivary cell line; cell proliferation ID SJOGRENS-SYNDROME; ACINAR-CELLS; EXPRESSION; PROTEIN; GROWTH; PROLIFERATION; ACTIVATION; ENTRY AB Interferon-gamma (IFN-gamma) +/- tumor necrosis factor-alpha (TNF-alpha) induces antiproliferation and intracellular Ca2+ store depletion in a human submandibular ductal cell line (HSG), which can be reversed on cytokine removal [A. J. Wu, G. C. Chen, B. J. Baum, and I. S. Ambudkar. Am. J. Physiol. 270 (Cell Physiol. 39): C514-C521, 1996]. Here we have examined a possible mechanism for the IFN-gamma-induced intracellular Ca2+ store depletion. There was a time-dependent decrease in thapsigargin-dependent internal Ca2+ release after exposure of the cells to the cytokines. The intracellular Ca2+ pump [sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)] protein in lysates and membranes of cells treated with IFN-gamma +/- TNF-alpha, but not with TNF-alpha alone, showed a similar time-dependent decrease (examined using a SERCA2 antibody). Removal of the cytokines, which resulted in recovery of cell growth and refill of internal Ca2+ stores, also increased the level of SERCA protein. The decrease in SERCA is not a result of decreased cell proliferation, since thapsigargin, 2,5-di-(t-butyl)-1,4-hydroquinone, or serum-free growth conditions induced antiproliferative effects on HSG cells without any corresponding decrease in SERCA. We suggest that the IFN-gamma-induced decrease in the level of SERCA accounts for the depleted state of internal Ca2+ stores in cytokine-treated HSG cells. These data suggest a novel mechanism for the inhibition of HSG cell growth by IFN-gamma. C1 NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Rm 1N-113,Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1997 VL 273 IS 6 BP C2030 EP C2036 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YM837 UT WOS:000071106400030 ER PT J AU Cohen, DM Bergman, RN AF Cohen, DM Bergman, RN TI Improved estimation of anaplerosis in heart using C-13 NMR SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Krebs cycle; citric acid cycle; tricarboxylic acid cycle; nuclear magnetic resonance spectroscopy; pyruvate; metabolism; isotopomer analysis; malate-aspartate shuttle ID TRICARBOXYLIC-ACID-CYCLE; PERFUSED RAT-HEART; POSITIONAL ISOTOPOMERS; PYRUVATE CARBOXYLATION; SUBSTRATE SELECTION; METABOLIC FLUX; WORKING HEART; AMINO-ACIDS; IN-VIVO; COMPARTMENTATION AB Anaplerotic enzymes, such as pyruvate carboxylase or malic enzyme, catalyze reactions that fill up the pools of the citric acid cycle (CAC), thereby increasing the total mass of CAC intermediates. Relative anaplerosis (y) denotes the ratio of anaplerotic flux to the flux catalyzed by citrate synthase. We examine conventional methods [C. R. Malloy, A. D. Sherry, and F. M. H. Jeffrey J. Biol. Chem. 263:6964-6971, 1988; C. R. Malloy; A. D. Sherry, and F. M. H. Jeffrey, Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H987-H995, 1990] of measurement of y using C-13-labeled precursors and analysis of [C-13]glutamate labeling by nuclear magnetic resonance (NMR) spectroscopy. Through mathematical analysis and computer simulation, we show that isotropic enrichment of the pool of pyruvate that is substrate for anaplerosis will severely decrease the accuracy of estimates of y made with conventional methods no matter how small the mass of the pool of pyruvate. Suppose that the recycling parameter R denotes the fraction of molecules of pyruvate that contain carbons derived from intermediates of the CAC. Each means of estimation of relative anaplerosis in the peer-reviewed literature assumes that R = 0, although this assumption has not been confirmed by experiment. We show that conventional formulas, using either fractional enrichments of carbons or isotopomer analysis, actually estimate at most y.(1 - R) instead of y during administration of [2-C-13]acetate and unlabeled pyruvate. Using a new formula for estimation of y, we recalculate values of y from the literature and find them similar to 50% too low. We assume that all anaplerosis is via pyruvate and that the difference in isotopic enrichment between cytosolic and mitochondrial malate is negligible. C1 Univ So Calif, Metab Res Unit, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Cohen, DM (reprint author), NIH, Cerebral Metab Lab, Bldg 36,Rm 1A-07, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG-00093]; NIADDK NIH HHS [AM-27619] NR 34 TC 14 Z9 14 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 DEC PY 1997 VL 273 IS 6 BP E1228 EP E1242 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA YM202 UT WOS:000071040000024 PM 9435540 ER PT J AU van Zijl, PCM Davis, D Eleff, SM Moonen, CTW Parker, RJ Strong, JM AF van Zijl, PCM Davis, D Eleff, SM Moonen, CTW Parker, RJ Strong, JM TI Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article; Proceedings Paper CT Joint Meeting of the Society-of-Magnetic-Resonance / European-Society-for-Magnetic-Resonance-in-Medicine-and-Biology CY 1995 CL NICE, FRANCE SP Soc Magnet Resonance, European Soc Magnet Resonance Med & Biol DE [C-13]glucose utilization; brain; Michaelis-Menten kinetics; cat; nuclear magnetic resonance spectroscopy ID C-13 NMR-SPECTROSCOPY; BLOOD-BRAIN-BARRIER; RAT-BRAIN; LUMPED CONSTANT; INVIVO; PHOSPHORYLATION; DEOXYGLUCOSE; GLUTAMATE; H-1-NMR; GLIOMA AB A new in vivo nuclear magnetic resonance (NMR) spectroscopy method is introduced that dynamically measures cerebral utilization of magnetically labeled [1-C-13]glucose from the change in total brain glucose signals on infusion, Kinetic equations are derived using a four-compartment model incorporating glucose transport and phosphorylation. Brain extract data show that the glucose B-phosphate concentration is negligible relative to glucose, simplifying the kinetics to three compartments and allowing direct determination of the glucose-utilization half-life time [t(1/2) = 1n2/(k(2) + k(3))] from the time dependence of the NMR signal. Results on isofluorane (n = 5)- and halothane (n = 7)- anesthetized cats give a hyperglycemic t(1/2) = 5.10 +/- 0.11 min(-1) (SE). Using Michaelis-Menten kinetics and an assumed half-saturation constant K-t = 5 +/- 1 mM, we determined a maximal transport, rate T-max = 0.83 +/- 0.19 mu mol.g(-1).min(-1), a cerebral metabolic rate of glucose CMRGlc = 0.22 +/- 0.03 mu mol.g(-1).min(-1), and a normoglycemic cerebral influx rate CIRGlc = 0.37 +/- 0.05 mu mol.g(-1).min(-1). Possible extension of this approach to positron emission tomography and proton NMR is discussed. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care, Baltimore, MD 21205 USA. NIH, In Vivo Nucl Magnet Resonance Res Ctr, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off Res Resources, Div Clin Pharmacol, Rockville, MD 20850 USA. Univ Victor Segalen 2, Unite Mixte Rech Resonance Magnet Syst Biol 5536, CNRS, F-33076 Bordeaux, France. RP van Zijl, PCM (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, 217 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI van Zijl, Peter/B-8680-2008 FU NINDS NIH HHS [NS-31490] NR 31 TC 22 Z9 22 U1 0 U2 2 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 DEC PY 1997 VL 273 IS 6 BP E1216 EP E1227 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA YM202 UT WOS:000071040000023 PM 9435539 ER PT J AU Yasuma, Y McCarron, RM Spatz, M Hallenbeck, JM AF Yasuma, Y McCarron, RM Spatz, M Hallenbeck, JM TI Effects of plasma from hibernating ground squirrels on monocyte-endothelial cell adhesive interactions SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE adhesion; endothelial cells; hibernation; intercellular adhesion molecule-1; stroke ID CEREBRAL-ARTERY OCCLUSION; POLYMORPHONUCLEAR LEUKOCYTES; REPERFUSION INJURY; AIR-EMBOLISM; BLOOD-FLOW; ISCHEMIA; BRAIN; RAT; TISSUE; INDUCTION AB Adhesion and subsequent penetration of leukocytes into central nervous system ischemic tissue proceeds via a coordinated inflammatory mechanism involving adhesion molecules at the blood-endothelium interface. Mammalian hibernation is a state of natural tolerance to severely reduced blood flow-oxygen delivery (i.e., ischemia). Hibernating thirteen-lined ground squirrels were investigated in an attempt to identify factors responsible for regulating this tolerance. Since leukocytopenia is closely associated with entrance into hibernation, the role of leukocyte adhesion to endothelium in this phenomenon was examined. Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelium and regulates interactions with circulating leukocytes that may result in margination or extravasation. ICAM-1 expression by rat cerebral microvascular endothelial cells (EC) cultured with plasma from hibernating (HP) or nonhibernating (NHP) thirteen-lined ground squirrels was dose dependently increased by HP and, to a lesser extent, by NHP. Treatment of EC with HP coincidentally induced significantly greater increases in monocyte adhesion to EC (37.2%) than were observed with NHP (23.9%). Study of the effects of HP and NHP on monocyte adhesion to EC may identify mechanisms responsible for ischemic tolerance in hibernators and could lead to the development of novel therapeutic approaches to the treatment of stroke. C1 NINDS, Stroke Branch, Bethesda, MD 20892 USA. RP McCarron, RM (reprint author), NINDS, Stroke Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 47 TC 20 Z9 20 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1997 VL 273 IS 6 BP R1861 EP R1869 PG 9 WC Physiology SC Physiology GA YP018 UT WOS:000071233000004 PM 9435638 ER PT J AU Burg, MB Peters, EM AF Burg, MB Peters, EM TI Urea and methylamines have similar effects on aldose reductase activity SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glycerophosphorylcholine; betaine; sorbitol; taurine; inositol; counteracting organic osmolytes ID MEDULLARY ORGANIC OSMOLYTES; ELASMOBRANCH FISHES; PROTEIN; INHIBITION; CELLS; NACL; PH AB The concentration of urea in renal medullary cells is sufficiently high to inhibit activity of many enzymes, yet the cells survive and function. The generally accepted explanation is the counteracting osmolytes hypothesis, which holds that methylamines, such as glycerophosphorylcholine (GPC) and glycine betaine (betaine), found in the renal medulla stabilize biological macromolecules and oppose the effects of urea. The present study tests this hypothesis by determining the effects of urea and methylamines, singly and in combination, on the activity of aldose reductase, an enzyme that is important in renal medullas for catalyzing production of sorbitol from glucose. In apparent contradiction to the counteracting osmolytes hypothesis, urea (1.0 M) and three different methylamines (trimethylamine N-oxide, betaine, and GPC; 0.5 M) all have similar and partially additive inhibitory effects. They all decrease substantially both the Michaelis constant (K(m)) and the maximum velocity (V(max)). Also, a high concentration (0.5 M) of other organic osmolytes that are abundant in the renal medulla, namely inositol, sorbitol, or taurine, has a similar but lesser effect. KCl(0.3 M) causes a small increase in activity We discuss the significance of these findings with regard to function of aldose reductase in the renal medulla and the counteracting osmolytes hypothesis. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 9,Rm 1N105, Bethesda, MD 20892 USA. NR 26 TC 24 Z9 24 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 1997 VL 273 IS 6 BP F1048 EP F1053 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YM642 UT WOS:000071085200024 ER PT J AU Jacobsen, LK Giedd, JN Berquin, PC Krain, AL Hamburger, SD Kumra, S Rapoport, JL AF Jacobsen, LK Giedd, JN Berquin, PC Krain, AL Hamburger, SD Kumra, S Rapoport, JL TI Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BASAL GANGLIA; RAT-BRAIN; CHILDREN; HALOPERIDOL; TOMOGRAPHY; METABOLISM; HYPOPLASIA; DIAGNOSIS; DISORDERS; CORTEX AB Objective: Studies have suggested that the maldeveloped neural circuitry producing schizophrenic symptoms may include the cerebellum. The authors found further support for this hypothesis by examining cerebellar morphology in severely ill children and adolescents with childhood-onset schizophrenia. Method: Anatomic brain scans were acquired with a 1.5-T magnetic resonance imaging scanner for 24 patients (mean age = 14.1 years, SD = 2.2) with onset of schizophrenia by age 12 (mean age at onset = 10.0 years, SD = 1.9) and 52 healthy children. Volumes of the vermis, inferior posterior lobe, fourth ventricle, and total cerebellum and the midsagittal area of the vermis were measured manually. Results: After adjustment for total cerebral volume, the volume of the vermis and the midsagittal area and volume of the inferior posterior lobe remained significantly smaller in the schizophrenic patients. There was no group difference in total cerebellar or fourth ventricle volume. Conclusions: These findings are consistent with observations of small vermal size in adult schizophrenia and provide further support for abnormal cerebellar Junction in childhood-and adult-onset schizophrenia. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,RM 6N240,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Roy, Amy/J-7613-2013; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 67 TC 95 Z9 96 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 DEC PY 1997 VL 154 IS 12 BP 1663 EP 1669 PG 7 WC Psychiatry SC Psychiatry GA YJ482 UT WOS:A1997YJ48200006 PM 9396943 ER PT J AU Bloch, M Schmidt, PJ Rubinow, DR AF Bloch, M Schmidt, PJ Rubinow, DR TI Premenstrual syndrome: Evidence for symptom stability across cycles SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID EPISODES; COMPLAINTS; DISORDER AB Objective: This study assessed cycle to cycle symptom stability in women with premenstrual syndrome (PMS). Method: Symptom ratings obtained prospectively over three or more symptomatic cycles from 16 women with PMS were analyzed. Measures of symptom severity and change were used to generate a coefficient of variation and an intraclass correlation coefficient (ICC) for each one of 14 symptoms across all cycles. In addition, symptoms were divided into three clusters, and the stability of the rank order of severity of symptoms within clusters and the correlation between symptom clusters were also calculated. Results: In the 65 cycles studied, mood symptoms were the most prevalent. Mood symptoms-anxiety, irritability, and mood lability-had the lowest coefficients of variation but also the lowest ICCs of all symptoms. Within their respective symptom clusters, both physical and mood symptoms showed remarkable stability across cycles of their rank order of severity, but only the mood symptom cluster was highly correlated with functional impairment. Conclusions: Three mood symptoms-anxiety, irritability, and mood lability-were the most stable symptoms in this group of women with PMS. Mood and not somatic symptoms accounted for most of the functional impairment in this group of women. It is concluded that PMS is a stable syndrome that may best be viewed as part of the spectrum of recurrent mood disorders. C1 NIMH,BEHAV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 14 TC 65 Z9 67 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1997 VL 154 IS 12 BP 1741 EP 1746 PG 6 WC Psychiatry SC Psychiatry GA YJ482 UT WOS:A1997YJ48200018 PM 9396955 ER PT J AU George, MS Wassermann, EM Kimbrell, TA Little, JT Williams, WE Danielson, AL Greenberg, BD Hallett, M Post, RM AF George, MS Wassermann, EM Kimbrell, TA Little, JT Williams, WE Danielson, AL Greenberg, BD Hallett, M Post, RM TI Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: A placebo-controlled crossover trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NY SP Amer Psychiat Assoc ID SIMPLE REACTION-TIME; MAJOR DEPRESSION; MOTOR CORTEX; INDUCTION; DISORDERS; ERRORS AB Objective: Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design. Method: Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment. Results: Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted. Conclusions: These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT RADIOL,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC. RP George, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,RM 3N212,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 365 Z9 372 U1 3 U2 10 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 DEC PY 1997 VL 154 IS 12 BP 1752 EP 1756 PG 5 WC Psychiatry SC Psychiatry GA YJ482 UT WOS:A1997YJ48200021 PM 9396958 ER PT J AU Constantino, JN Morris, JA Murphy, DL AF Constantino, JN Morris, JA Murphy, DL TI CSF 5-HIAA and family history of antisocial personality disorder in newborns SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEROTONIN AB Objective: The relationship between genetic liability for antisocial behavior and CSF 5-hydroxyindoleacetic acid (5-HIAA) in newborns was explored. Method: The authors assayed S-HIAA in ''leftover'' CSF from 193 neurologically normal newborns and obtained family psychiatric histories of the newborns' first-and second-degree relatives. Results: Levels of S-HIAA were significantly lower In the infants with family histories of antisocial personality disorder than in the newborns without such family histories, Conclusions: These findings support the possibility that serotonin mediates one component of genetic liability to antisocial outcome, but the magnitude of that component may be less than what has been inferred from previously published reports. C1 WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Constantino, JN (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,4940 CHILDRENS PL,ST LOUIS,MO 63110, USA. FU NIMH NIH HHS [MH-56317] NR 6 TC 29 Z9 31 U1 4 U2 7 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 DEC PY 1997 VL 154 IS 12 BP 1771 EP 1773 PG 3 WC Psychiatry SC Psychiatry GA YJ482 UT WOS:A1997YJ48200027 PM 9396964 ER PT J AU Read, JS Troendle, JF Klebanoff, MA AF Read, JS Troendle, JF Klebanoff, MA TI Cause-of-death categories - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 NICHD, CRMC, PAMA, NIH, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHD, CRMC, PAMA, NIH, 6100 Execut Blvd,Room 4B11F, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1997 VL 87 IS 12 BP 2055 EP 2055 DI 10.2105/AJPH.87.12.2055 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YP420 UT WOS:000071275000037 ER PT J AU Kari, F Hatch, G Slade, R Crissman, K Simeonova, PP Luster, M AF Kari, F Hatch, G Slade, R Crissman, K Simeonova, PP Luster, M TI Dietary restriction mitigates ozone-induced lung inflammation in rats: A role for endogenous antioxidants SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID FOOD RESTRICTION; BRONCHOALVEOLAR LAVAGE; ASCORBIC-ACID; GUINEA-PIGS; TRANSPORT; ENZYMES; LIVER; ACCUMULATION; EXPRESSION; SUBSTANCES AB Studies were undertaken to determine whether dietary restriction protects against acute pulmonary oxidant challenge, Male F344 rats were ed NIH-31 diet either ad libitum or at restricted levels equal to 75% that of ad libitum intake. After 3 wk of dietary adaptation, animals were exposed by inhalation to 2.0 ppm ozone (O-3) for 2 h or chamber air and evaluated for cellular and biochemical indices of pulmonary toxicity. Compared to air controls, bronchoalveolar lavage fluid (BALF) from O-3 exposed ad libitum fed rats contained increased protein (145 versus 380 mu g/ml), PMN infiltration (0 versus 11%) and fibronectin (45 versus 607 U/ml). Diet restriction abrogated these indicators of pulmonary inflammation induced by ozone. Binding of O-18(3) to BALF protein and cells was significantly decreased in diet restricted rats while BALF ascorbate and glutathione levels, bill not alpha-tocopherol or urate, were elevated compared to an libitum fed rats. Taken together, these results indicate that dietary restriction affords protection against O-3-induced oxidant toxicity. Protection is mediated partially by increases in ascorbate in the fluid bathing the lung surface, thereby providing an antioxidant sink which minimizes the ability of O-3 to reach biological targets. C1 NIOSH, Hlth Effects Res Lab, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. US EPA, Hlth Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Environm Immunol & Neurobiol Sect, Res Triangle Pk, NC 27709 USA. RP Luster, M (reprint author), NIOSH, Hlth Effects Res Lab, Toxicol & Mol Biol Branch, 1095 Willowdale Rd,Mailstop 3014, Morgantown, WV 26505 USA. NR 37 TC 28 Z9 28 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 1997 VL 17 IS 6 BP 740 EP 747 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA YL873 UT WOS:000071002400010 PM 9409561 ER PT J AU Li, J Wirtz, RA McCutchan, TF AF Li, J Wirtz, RA McCutchan, TF TI Analysis of malaria parasite RNA from decade-old Giemsa-stained blood smears and dried mosquitoes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM; RIBOSOMAL-RNA AB We have analyzed RNA isolated from recently prepared and historically preserved slides containing smears of Plasmodium-infected blood. We found that slides preserved as long as 20 years can yield RNA that is a suitable template for polymerase chain reaction (PCR) amplification. Mosquitoes that have been stored for years under ambient temperature can also be used as an RNA source. The RNA amplification from slide-derived material is shown to be dependent upon the addition of reverse transcriptase and the resultant products are specific to the developmental state of the parasite. Amplification of ribosomal RNA with primers conserved for Plasmodium and hybridization with species-specific probes provide a general, unbiased method for species determination. Messenger RNA transcripts from slides also appear to serve as templates. The procedure may add complementary information to that derived from microscopic examination of Giemsa-stained blood smears including species identification, variant antigen identification and drug resistance status. C1 NIAID, Parasit Dis Lab, Growth & Dev Sect, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Div Communicable Dis & Immunol, Washington, DC 20307 USA. RP McCutchan, TF (reprint author), NIAID, Parasit Dis Lab, Growth & Dev Sect, Bldg 4,Room B1-28,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 16 Z9 17 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 1997 VL 57 IS 6 BP 727 EP 731 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA YQ731 UT WOS:000071417600020 PM 9430536 ER PT J AU Kim, IH Rodgers, GP AF Kim, IH Rodgers, GP TI In vivo footprinting using N-ethyl,N-nitrosourea: Improved resolution of the DNA-protein interactions in the human gamma-globin gene promoter region SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID FETAL HEMOGLOBIN PRODUCTION; SICKLE-CELL-ANEMIA; POLYMERASE CHAIN-REACTION; STAGE SELECTOR ELEMENT; IN-VIVO; TRANSCRIPTION FACTORS; BINDING; HYDROXYUREA; INVIVO; METHYLATION AB N-Ethyl, N-nitrosourea (ENU) was used as a probing agent in conjunction with a modified ligation-mediated polymerase chain reaction in a new in vivo footprinting procedure, In the present work, we examined the promoter region of the human gamma-globin gene under both uninduced and hemin-induced conditions in K562 cells. In the course of comparing this method with the standard dimethyl sulfate (DMS) in vivo method and previously reported results, we were able to verify our new method. However, discrepancies between these methods were observed at the stage selector element, -50 region, of gamma-globin promoter. Our in vivo footprinting result showed DNA-protein interaction at this region under the hemin-induced condition which was not revealed by the conventional DMS in vivo footprinting method. This approach, using ENU-modified in vivo footprinting, is now being applied to clarify the mechanism of cytotoxic drug-induced fetal hemoglobin augmentation. C1 NIDDK,MOL HEMATOL SECT,BIOL CHEM LAB,BETHESDA,MD 20892. RP Kim, IH (reprint author), DONG A UNIV,COLL MED,DEPT BIOCHEM,PUSAN 602103,SOUTH KOREA. NR 41 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 1997 VL 254 IS 1 BP 1 EP 8 DI 10.1006/abio.1997.2403 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YK715 UT WOS:A1997YK71500001 PM 9398338 ER PT J AU Tifft, CJ Proia, RL AF Tifft, CJ Proia, RL TI The beta-hexosaminidase deficiency disorders: Development of a clinical paradigm in the mouse SO ANNALS OF MEDICINE LA English DT Article; Proceedings Paper CT International Ulla Hjelt Symposium on Gene Therapy of Single-Gene Disorders CY JUN 07-10, 1997 CL TUUSULA, FINLAND SP Fdn Pediat Res DE animal models; G(M2) gangliosidosis; lysosomal storage diseases; mucopolysaccharidosis; Sandhoff disease; Tay-Sachs disease ID TAY-SACHS-DISEASE; TARGETED DISRUPTION; HEXA GENE; MICE; NEUROPATHOLOGY; GANGLIOSIDOSIS AB Tay-Sachs disease and Sandhoff disease are severe neurodegenerative disorders caused by a deficiency of beta-hexosaminidase A and resultant accumulation of its substrate, G(M2) ganglioside, in neuronal lysosomes. The three clinical forms of the disorders (infantile, juvenile and adult) are of varying severity and onset, and have been correlated with the amount of residual G(M2) ganglioside-degrading activity present in patients' cells. Through targeted disruption of the murine beta-hexosaminidase genes in embryonic stem cells, we have developed a set of mice that vary in their G(M2) ganglioside-degrading capacity and exhibit many of the clinical features of the human diseases, These mice are valuable for the study of pathogenic mechanisms and for devising novel therapeutic strategies in these disorders. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. RP Proia, RL (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,MSC 1810,Room 9D-20,10 Ctr Dr, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 16 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PD DEC PY 1997 VL 29 IS 6 BP 557 EP 561 DI 10.3109/07853899709007482 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZG926 UT WOS:000073053900014 PM 9562524 ER PT J AU Pass, HI Temeck, BK Kranda, K Thomas, G Russo, A Smith, P Friauf, W Steinberg, SM AF Pass, HI Temeck, BK Kranda, K Thomas, G Russo, A Smith, P Friauf, W Steinberg, SM TI Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 20-23, 1997 CL CHICAGO, IL SP Soc Surg Oncol DE mesothelioma; photodynamic therapy; immunochemotherapy; Phase III ID DIFFUSE AB Background: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease, This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (I) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence or survival. Methods: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT, The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology. Results: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT), There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT: 21; no PDT, 17; stage IV PDT, 0: no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. Conclusions: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM. C1 NCI,THORAC ONCOL SECT,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,NIH,BETHESDA,MD. NCI,RADIAT BIOL SECT,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,NIH,BETHESDA,MD. NCI,BIOSTAT & DATA MANAGEMENT SECT,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,NIH,BETHESDA,MD. NR 15 TC 101 Z9 102 U1 0 U2 1 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 DEC PY 1997 VL 4 IS 8 BP 628 EP 633 DI 10.1007/BF02303746 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA YL103 UT WOS:A1997YL10300005 PM 9416409 ER PT J AU Kunkel, MW Kirkpatrick, DL Johnson, JI Powis, G AF Kunkel, MW Kirkpatrick, DL Johnson, JI Powis, G TI Cell line-directed screening assay for inhibitors of thioredoxin reductase signaling as potential anti-cancer drugs SO ANTI-CANCER DRUG DESIGN LA English DT Article DE cancer; COMPARE; screening; thioredoxin; thioredoxin reductase ID LEUKEMIA-DERIVED FACTOR; AUTOCRINE GROWTH-FACTOR; SECRETION; PURIFICATION; FEASIBILITY; ACTIVATION; EXPRESSION; PATTERNS; HOMOLOG; PANEL AB We have used a cell line-directed screening approach (CDSA) to identify novel inhibitors of the thioredoxin reductase signaling pathway which contributes to the transformed phenotype of some human tumors. Two 2-imidazolyl disulfide compounds, previously identified as inhibitors of thioredoxin reductase, were screened for growth inhibitory activity in the National Cancer Institute (NCI) human cancer cell line panel. The COMPARE pattern recognition algorithm was used to identify similar compounds from >60 000 compounds in the NCI investigational drug database. Of 47 nondiscreet compounds tested in a thioredoxin reductase/thioredoxin insulin reduction assay, 37 (77%) were inhibitors with IC(50)s less than or equal to 10 mu g/ml and 15 of those (32%) had IC(50)s less than or equal to 1 mu g/ml. These compounds were all as selective or more selective for thioredoxin reductase than for glutathione reductase, while three compounds were inhibitors of thioredoxin. In comparison to CDSA, the number of compounds with IC(50)s less than or equal to 1 mu g/ml identified by screening of 52 compounds from the database whose growth inhibiting activity was unrelated to the activity of the disulfide compounds was only 2%. Screening of 221 randomly selected natural products gave only 3% of compounds with IC(50)s less than or equal to 1 mu g/ml. Thus, the CDSA using data from the NCI cancer cell panel and known inhibitors of the selected target as seed compounds can greatly increase hit rates, compared with random screening, for identifying novel inhibitors of a target, in this case thioredoxin signaling. C1 Univ Arizona, Arizona Canc Ctr, Hlth Sci Ctr, Tucson, AZ 85724 USA. Univ Regina, Dept Chem, Regina, SK S4S 0A2, Canada. NCI, Div Canc Treatment, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Powis, G (reprint author), Univ Arizona, Arizona Canc Ctr, Hlth Sci Ctr, 1515 N Campbell Ave, Tucson, AZ 85724 USA. FU NCI NIH HHS [CA48725, CA52995, CA42286] NR 33 TC 51 Z9 52 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD DEC PY 1997 VL 12 IS 8 BP 659 EP 670 PG 12 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA YT163 UT WOS:000071571300005 PM 9448705 ER PT J AU Piscitelli, SC Figg, WD Hahn, B Kelly, G Thomas, S Walker, RE AF Piscitelli, SC Figg, WD Hahn, B Kelly, G Thomas, S Walker, RE TI Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NECROSIS-FACTOR-ALPHA; PLASMA; TYPE-1 AB The pharmacokinetics of thalidomide in nine human immunodeficiency virus-infected patients were studied. Single doses of thalidomide were well absorbed, with mean peak concentrations (+/- standard deviations) of 1.17 +/- 0.21 and 3.47 +/- 1.14 mu g/ml in the 100- and 300-mg dosing groups, respectively, and the mean elimination half-life was approximately 6 h. Adverse effects were mild, with drowsiness being reported for seven of nine patients. C1 NCI,CLIN PHARMACOKINET SECT,NIH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. CELGENE CORP,WARREN,NJ. RP Piscitelli, SC (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM 1N257,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 21 TC 39 Z9 41 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 DEC PY 1997 VL 41 IS 12 BP 2797 EP 2799 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YK234 UT WOS:A1997YK23400040 PM 9420064 ER PT J AU Karamychev, VN Panyutin, IG Reed, MW Neumann, RD AF Karamychev, VN Panyutin, IG Reed, MW Neumann, RD TI Effect of radionuclide linker structure on DNA cleavage by I-125-labeled oligonucleotides SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID OLIGODEOXYNUCLEOTIDES; RADIOTOXICITY; BINDING AB We studied the yield and distribution of DNA strand breaks produced by decay of I-125 introduced into triplex-forming and duplex-forming oligodeoxyribonucleotide (ODNs) through linkers of various lengths. ODNs were prepared with I-125 attached at the 5'-end with a long linker or to an internal nucleotide position with a short linker, The I-125-ODNs were hybridized to either a single-stranded target to form duplexes or to a double-stranded target to form triplexes, After decay accumulation, the duplex and tripler samples were assayed for strand breaks in a sequencing gel, The yield of strand breaks per decay was 0.34 for duplex with the 5'-modified ODN and 0.66 for duplex with internally modified ODN, The tripler samples with internal I-125 have different yields of DNA breaks in the pyrimidine and purine strands, 0.16 and 0.37, respectively, The yield of DNA breaks in the pyrimidine strand of the tripler with the 5'-modified ODN is 0.46, The majority of breaks are located within 5 nucleotides from the decay site, The yield of strand cleavage per decay of I-125 was nearly two-fold lower with the described linkers in comparison with the results obtained when I-125 is directly attached to the C-5 position of cytosine, Nevertheless, the rapid iodination procedure reported here combined with the possibility of multiple incorporations of I-125 On the linkers makes such I-125-ODNs promising agents for sequence-specific cleavage of DNA. C1 NIH, NMD, CC, Dept Nucl Med,Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Novosibirsk Bioorgan Chem Inst, Novosibirsk 630090, Russia. Epoch Pharmaceut Inc, Bothell, WA 98021 USA. RP Neumann, RD (reprint author), NIH, NMD, CC, Dept Nucl Med,Warren G Magnuson Clin Ctr, 10 Ctr Dr,Msc 1180, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD DEC PY 1997 VL 7 IS 6 BP 549 EP 557 DI 10.1089/oli.1.1997.7.549 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA YP193 UT WOS:000071251900003 PM 9450912 ER PT J AU Yusa, K Kavlick, MF Kosalaraksa, P Mitsuya, H AF Yusa, K Kavlick, MF Kosalaraksa, P Mitsuya, H TI HIV-1 acquires resistance to two classes of antiviral drugs through homologous recombination SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1; resistance; antiviral drugs; homologous recombination ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; SIMULTANEOUS ZIDOVUDINE; DIDANOSINE THERAPY; CUBIC MILLIMETER; INFECTED ADULTS; INHIBITORS; MUTATIONS; AZT AB Genetic recombination contributes to the genomic heterogeneity of human immunodeficiency virus type 1 (HIV-1). In the present study, we demonstrate that HIV-1 readily develops resistance to two classes of anti-HIV-1 drugs through in vitro genetic recombination involving large segments of the viral genome. Co-transfection of COS-7 cells with an HIV-1 plasmid (pSUM13) carrying five mutations in the reverse transcriptase (RT)-encoding region (A62V, V75I, F77L, F116Y, Q151M), conferring resistance to multiple dideoxynucleoside analogs (ddNs), and another HIV-1 plasmid (pSUM431) carrying five mutations in the protease-encoding region (V32I, L33F, K45I, I84V, L89M), conferring resistance to protease inhibitors such as KNI-272, readily produced HIV-1 carrying both sets of mutations when propagated in MT-2 cells in the presence of azidothymidine (AZT) and KNI-272. The resultant HIV-1 variant was highly resistant to both ddNs and KNI-272. Co-infection of MT-2 cells with HIV-1(SUM13) carrying the RT mutations and HIV-1(SUM431) carrying the mutations in the protease also generated HIV-1 with both sets of mutations when cultured with AZT and KNI-272. We also report here that the problematic artifactual recombination occurring during genetic analyses of heterogeneous nucleic acid sequences using polymerase chain reaction can be successfully obviated. (C) 1997 Elsevier Science B.V. C1 NCI, Expt Retrovirol Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, Div Clin Sci, NIH, Bldg 10,Room 5A11, Bethesda, MD 20892 USA. EM hmitsuya@helix.nih.gov NR 38 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 1997 VL 36 IS 3 BP 179 EP 189 DI 10.1016/S0166-3542(97)00053-3 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA YR457 UT WOS:000071497200004 PM 9477118 ER PT J AU Rumsey, JM Donohue, BC Brady, DR Nace, K Giedd, JN Andreason, P AF Rumsey, JM Donohue, BC Brady, DR Nace, K Giedd, JN Andreason, P TI A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL ASYMMETRY; LANGUAGE IMPAIRMENT; BRAIN MORPHOLOGY; MRI; HANDEDNESS; DISORDERS; CHILDREN; CORTEX; SCHIZOPHRENIA; DISABILITIES AB Background: Imaging studies have suggested anomalous anatomical asymmetries in language-related regions of the temporal and parietal lobes in individuals with developmental dyslexia. Autopsy studies have reported unusual symmetry of the planum temporale (PT) in patients with dyslexia. Methodological limitations characterize much of this literature, however. Objective: To examine the size and asymmetry of the PT and its extension into the parietal lobe (planum parietale [PP]) in men with well-characterized, persistent dyslexia by using magnetic resonance imaging and 3-dimensional surface rendering techniques. Methods: The brains of 16 right-handed dyslexic men aged 18 to 40)rears and 14 matched control subjects were studied with magnetic resonance imaging. Most of these subjects were previously studied with positron emission tomography, which demonstrated functional abnormalities in temporal and parietal brain regions in the dyslexic group. The area of the PT was determined with the aid of 3-dimensional surface-rendering techniques. The size of the PP was estimated by measuring the length of the posterior ascending ramus on 3 parasagittal slices. Results: Approximately 70% to 80% of both groups showed equivalent leftward (left>right) asymmetries of the PT; approximately 50% to 60% showed equivalent rightward (right>left) asymmetries of the PP. These asymmetries showed equivalent moderate inverse correlations with each other in both groups. Conclusions: These results challenge the notion that anomalous asymmetry of the PT is strongly associated with developmental dyslexia. Given the heterogeneity of the dyslexic population, some subgroup of dyslexic individuals tie, those with developmental language disorders) may show unusual symmetry or reversed asymmetry in this region. However, anomalous asymmetry of the planum did not contribute to functional abnormalities demonstrated in these patients by positron emission tomography. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. US FDA, DIV NEUROPHARMACOL DRUG PROD, ROCKVILLE, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. 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 55 TC 99 Z9 99 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1997 VL 54 IS 12 BP 1481 EP 1489 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA YJ960 UT WOS:A1997YJ96000006 PM 9400357 ER PT J AU Lewis, RA CarrHolden, LM Doyle, K Fainstein, V Gardner, N Gross, R OrengoNania, S Patel, V Samo, TC Shigley, JW Shawver, L Spencer, SS Weinert, M Martin, DF Gibbs, D Jernigan, J Dunn, JP Bartlett, J Becker, R Jabs, DA Johnson, DA LaSalvia, S Leslie, J Maenza, J Miller, T Neisser, LG Semba, RD Tucker, P Barron, B Jarrott, C Peyman, G Swenie, D Heinemann, MH Janis, R Polsky, B Sepkowitz, K Friedman, AH Ginsburg, R Severin, C Teich, S Wallach, F Rescigno, R PaezBoham, R Buroff, E Kloser, P Wanner, M Friedberg, DN Addessi, A Chachoua, A Dieterich, D Hill, J Hutt, R Kaul, A Ligh, J LorenzoLatkany, M Pei, M Powers, T Weinberg, DV Jampol, EM Lyon, AT Munana, A Murphy, R Palella, F Richine, L Strugala, Z Valadez, G Holland, GN Carlson, ME Chafey, SA Hardy, WD Johiro, AK MacArthurChang, LJ Martin, MA Moe, AA Strong, CA Tufail, A Ugalat, PS Weisz, JM Freeman, WR ArevaloColina, JF Clark, T Jarman, CL Meixner, L Meng, TC Spector, S Taskintuna, I Torriani, FJ ODonnell, J Alfred, P Ballesteros, F Clay, D Coleman, R Gordon, K Gumbley, D Hoffman, J Irvine, A Jacobson, M Larson, M Macalalag, L Narahara, M Payne, M Seiff, S Wilson, S Woodring, H Davis, J Blenke, A Madera, I Mendez, P Murray, T vanderHorst, C Kylstra, J Wohl, D Ziman, K Pavan, PR Grizzard, WS Bergen, GA Cohen, SM Craig, JA Dehler, RL Elbert, E Fox, RW Hammer, ME Hernandez, LS Herrera, S Holt, D Kemp, S Larkin, JA Ledford, DK Lockey, RF Menosky, MM Millard, S Nadler, JP Nelson, RP Norris, D Ormerod, LD Pautler, SE Poblete, SJ Rodriguez, D Rosenbach, KP Seekins, DW Toney, JR Dodge, JM Klemstine, JL Schuerholtz, TA Stevens, M Meinert, CL AmendLibercci, D Coleson, L Collins, KL Collison, BJ Dawson, C Dodge, J Donithan, M Ewing, C Fink, N Gerczak, C Harle, J Holbrook, JT Huffman, R Isaacson, MR Gilpin, AMK Lane, M Levine, CR Martin, B Meinert, J Min, N Nowakowski, DJ Owens, RM Oziemkowska, MJ Piantadosi, B Saah, A Smith, M Tonascia, J VanNatta, ML Davis, MD Armstrong, J Brickbauer, J Brothers, R Chop, M Hubbard, L Hurlburt, D Kastorff, L Neider, M Onofrey, J Stoppenbach, V VanderhoofYoung, M Walls, M Hughes, R Kurinij, N Mowery, RL Alston, B Foulkes, M Nadler, PI Wood, DL Bladet, M Wu, N Clark, T Feinberg, J Freeman, W Holbrook, J McArthurChang, L Duncan, WR Kessler, H Lambert, AG Powderly, W Schnittman, S Spector, S Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, JP Smith, H Whitley, R Cheng, B Frost, K Marco, M AF Lewis, RA CarrHolden, LM Doyle, K Fainstein, V Gardner, N Gross, R OrengoNania, S Patel, V Samo, TC Shigley, JW Shawver, L Spencer, SS Weinert, M Martin, DF Gibbs, D Jernigan, J Dunn, JP Bartlett, J Becker, R Jabs, DA Johnson, DA LaSalvia, S Leslie, J Maenza, J Miller, T Neisser, LG Semba, RD Tucker, P Barron, B Jarrott, C Peyman, G Swenie, D Heinemann, MH Janis, R Polsky, B Sepkowitz, K Friedman, AH Ginsburg, R Severin, C Teich, S Wallach, F Rescigno, R PaezBoham, R Buroff, E Kloser, P Wanner, M Friedberg, DN Addessi, A Chachoua, A Dieterich, D Hill, J Hutt, R Kaul, A Ligh, J LorenzoLatkany, M Pei, M Powers, T Weinberg, DV Jampol, EM Lyon, AT Munana, A Murphy, R Palella, F Richine, L Strugala, Z Valadez, G Holland, GN Carlson, ME Chafey, SA Hardy, WD Johiro, AK MacArthurChang, LJ Martin, MA Moe, AA Strong, CA Tufail, A Ugalat, PS Weisz, JM Freeman, WR ArevaloColina, JF Clark, T Jarman, CL Meixner, L Meng, TC Spector, S Taskintuna, I Torriani, FJ ODonnell, J Alfred, P Ballesteros, F Clay, D Coleman, R Gordon, K Gumbley, D Hoffman, J Irvine, A Jacobson, M Larson, M Macalalag, L Narahara, M Payne, M Seiff, S Wilson, S Woodring, H Davis, J Blenke, A Madera, I Mendez, P Murray, T vanderHorst, C Kylstra, J Wohl, D Ziman, K Pavan, PR Grizzard, WS Bergen, GA Cohen, SM Craig, JA Dehler, RL Elbert, E Fox, RW Hammer, ME Hernandez, LS Herrera, S Holt, D Kemp, S Larkin, JA Ledford, DK Lockey, RF Menosky, MM Millard, S Nadler, JP Nelson, RP Norris, D Ormerod, LD Pautler, SE Poblete, SJ Rodriguez, D Rosenbach, KP Seekins, DW Toney, JR Dodge, JM Klemstine, JL Schuerholtz, TA Stevens, M Meinert, CL AmendLibercci, D Coleson, L Collins, KL Collison, BJ Dawson, C Dodge, J Donithan, M Ewing, C Fink, N Gerczak, C Harle, J Holbrook, JT Huffman, R Isaacson, MR Gilpin, AMK Lane, M Levine, CR Martin, B Meinert, J Min, N Nowakowski, DJ Owens, RM Oziemkowska, MJ Piantadosi, B Saah, A Smith, M Tonascia, J VanNatta, ML Davis, MD Armstrong, J Brickbauer, J Brothers, R Chop, M Hubbard, L Hurlburt, D Kastorff, L Neider, M Onofrey, J Stoppenbach, V VanderhoofYoung, M Walls, M Hughes, R Kurinij, N Mowery, RL Alston, B Foulkes, M Nadler, PI Wood, DL Bladet, M Wu, N Clark, T Feinberg, J Freeman, W Holbrook, J McArthurChang, L Duncan, WR Kessler, H Lambert, AG Powderly, W Schnittman, S Spector, S Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, JP Smith, H Whitley, R Cheng, B Frost, K Marco, M TI MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency in syndrome - The monoclonal antibody cytomegalovirus retinitis trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NATURAL-HISTORY; VIRUS; GANCICLOVIR; AIDS; QUESTIONNAIRE; DISEASE; MODELS AB Objective: To evaluate the the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. Methods: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician. Results: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year, placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis. Conclusions: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,SOCA CHAIRMANS OFF,BALTIMORE,MD 21205. BAYLOR COLL MED,CULLEN EYE INST,HOUSTON,TX 77030. EMORY UNIV CLIN,ATLANTA,GA 30322. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. MT SINAI SCH MED,NEW YORK,NY. NEW JERSEY MED SCH,NEWARK,NJ. NYU MED CTR,NEW YORK,NY 10016. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MIAMI,SCH MED,MIAMI,FL. UNIV N CAROLINA,CHAPEL HILL,NC 27515. UNIV S FLORIDA,TAMPA,FL 33620. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,COORDINATING CTR,BALTIMORE,MD 21218. UNIV WISCONSIN,FUNDUS PHOTOGRAPH READING CTR,MADISON,WI. MCKESSON BIOSERV CORP,DRUG DISTRIBUT CTR,ROCKVILLE,MD. NEI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. PROT DESIGN LABS,MT VIEW,CA. NR 39 TC 30 Z9 30 U1 0 U2 4 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 DEC PY 1997 VL 115 IS 12 BP 1528 EP 1536 PG 9 WC Ophthalmology SC Ophthalmology GA YK251 UT WOS:A1997YK25100005 ER PT J AU Beck, RW Trobe, JD Moke, PS Brodsky, MC Buckley, EG Chrousos, GA Goodwin, JA Guy, JR Katz, B Kaufman, DI Keltner, JL Kupersmith, MJ Miller, NR OrengoNania, S Savino, PJ Shults, WT Smith, CH Thompson, HS Wall, M AF Beck, RW Trobe, JD Moke, PS Brodsky, MC Buckley, EG Chrousos, GA Goodwin, JA Guy, JR Katz, B Kaufman, DI Keltner, JL Kupersmith, MJ Miller, NR OrengoNania, S Savino, PJ Shults, WT Smith, CH Thompson, HS Wall, M TI Visual function 5 years after optic neuritis experience of the Optic Neuritis Treatment Trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; FOLLOW-UP; CORTICOSTEROIDS; PROGNOSIS; RECOVERY; EYE AB Objective: To assess the 5-year visual course, including the incidence of recurrent optic neuritis, in 454 patients enrolled in the Optic Neuritis Treatment Trial. Methods: Five-year follow-up vision testing, which included measures of visual acuity, contrast sensitivity, visual field, and color vision, was completed for 397 (87%) of the 454 patients. Results: Visual function test results in the eyes that experienced optic neuritis at study enrollment (affected eyes) were normal or only slightly abnormal after 5 years in most patients; the results did not significantly differ by treatment group (P=.37 for visual acuity). The visual acuity in the affected eyes was 20/25 or better in 87%, 20/25 to 20/40 in 7%, 20/50 to 20/190 in 3%, and 20/200 or worse in 3%. The recurrence of optic neuritis in either eye occurred in 28% of the patients and was more frequent in patients with multiple sclerosis (P=.001) and in patients without multiple sclerosis who were in the prednisone treatment group (P=.004). Most eyes with a recurrence retained normal or almost normal visual function. Conclusions: Most patients retained good to excellent vision in the 5 years following an attack of optic neuritis, even if the optic neuritis recurred. Recurrences were more frequent in patients with multiple sclerosis and in those treated with oral prednisone alone. The completion of the 5-year follow-up by the Optic Neuritis Treatment Trial cohort has nor altered our management recommendations based on the results we reported earlier. C1 UNIV ARKANSAS,LITTLE ROCK,AR 72204. BAYLOR COLL MED,HOUSTON,TX 77030. CALIF PACIFIC MED CTR,SAN FRANCISCO,CA. DUKE UNIV,DURHAM,NC. UNIV FLORIDA,GAINESVILLE,FL. GEORGETOWN UNIV,WASHINGTON,DC. UNIV ILLINOIS,CHICAGO,IL. UNIV IOWA,IOWA CITY,IA. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV MICHIGAN,ANN ARBOR,MI 48109. MICHIGAN STATE UNIV,E LANSING,MI 48824. NYU,NEW YORK,NY. DEVERS EYE INST,PORTLAND,OR. SWEDISH MED CTR,SEATTLE,WA. UNIV CALIF DAVIS,DAVIS,CA. NEI,BETHESDA,MD 20892. RP Beck, RW (reprint author), JAEB CTR HLTH RES,3010 E 138TH AVE,SUITE 9,TAMPA,FL 33613, USA. NR 25 TC 68 Z9 72 U1 0 U2 2 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 DEC PY 1997 VL 115 IS 12 BP 1545 EP 1552 PG 8 WC Ophthalmology SC Ophthalmology GA YK251 UT WOS:A1997YK25100007 ER PT J AU Chan, CC Matteson, DM Li, Q Whitcup, SM Nussenblatt, RB AF Chan, CC Matteson, DM Li, Q Whitcup, SM Nussenblatt, RB TI Apoptosis in patients with posterior uveitis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FAS-LIGAND; SYMPATHETIC OPHTHALMIA; SYSTEMIC AUTOIMMUNITY; CHORIORETINAL BIOPSY; DEATH FACTOR; DISEASE; EXPRESSION; CELLS; GLD; NECROSIS AB Background: Apoptosis plays a part in the pathogenesis of autoimmune diseases. Objective: To investigate the expression of apoptotic markers in the eyes of patients with uveitis. Methods: With the use of immunohistochemical and in situ apoptotic detection techniques, apoptotic molecules (Fas or Fas ligand [FasL]) and nuclear DNA fragmentation were examined in 8 enucleated eyes with Behcet's disease (1), sarcoidosis (1), subretinal fibrosis and uveitis (1), sympathetic ophthalmia (4), and the Vogt-Koyanagi-Harada syndrome (1); in 5 chorioretinal biopsy specimens with acute retinal necrosis (2), multifocal choroiditis (1), sarcoidosis (1), and subretinal fibrosis and uveitis (1); and in 3 normal control eyes. Results: Fas and FasL were constitutively expressed in the normal human retina, but they were expressed much less in the choroid. Increased expression of Fas and FasL was found in the retina, chorioretinal scar, and choroidal granulomas in uveitic eyes. However, Fas and FasL expression was absent in the biopsy specimens with acute retinal necrosis, and little Fas or FasL was noted on infiltrating lymphocytes. DNA fragmentation was also identified in eyes with chorioretinal scar and gliosis. Conclusions: Apoptosis occurs in uveitic eyes and may play a regulatory role in limiting ocular inflammation. In uveitic eyes, a dysregulation of the Fas-FasL apoptotic pathway may lead to gliosis and fibrosis. C1 NEI,CLIN BRANCH,NIH,BETHESDA,MD 20892. RP Chan, CC (reprint author), NEI,IMMUNOL LAB,NIH,10 CTR DR,MSC 1857,BLDG 10,ROOM 10N103,BETHESDA,MD 20892, USA. NR 40 TC 40 Z9 48 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 DEC PY 1997 VL 115 IS 12 BP 1559 EP 1567 PG 9 WC Ophthalmology SC Ophthalmology GA YK251 UT WOS:A1997YK25100009 PM 9400790 ER PT J AU Henson, DE Oberman, AA Hutter, RVP AF Henson, DE Oberman, AA Hutter, RVP TI Breast examination protocol: Why the nipple? Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 NCI, Early Detect Branch, NIH, Bethesda, MD 20892 USA. RP Henson, DE (reprint author), NCI, Early Detect Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1997 VL 121 IS 12 BP 1238 EP 1238 PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YP012 UT WOS:000071232400004 ER PT J AU Henson, DE AF Henson, DE TI On practice guidelines and outcomes SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID AUTOPSY PATHOLOGY; PRACTICE PROTOCOL; CHECKLISTS; CARCINOMA C1 NCI, Early Detect Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Henson, DE (reprint author), NCI, Early Detect Branch, Div Canc Prevent & Control, EPN Bldg,Room 330,6130 Execut Blvd,MSC 7346, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1997 VL 121 IS 12 BP 1239 EP 1240 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YP012 UT WOS:000071232400005 PM 9431311 ER PT J AU Compton, CC Henson, DE Hutter, RVP Sobin, LH Bowman, HE AF Compton, CC Henson, DE Hutter, RVP Sobin, LH Bowman, HE CA Canc Comm Coll Amer Pathol TI Updated protocol for the examination of specimens removed from patients with colorectal carcinoma - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID LARGE BOWEL-CANCER; TUMOR STUDY-GROUP; SURGICAL PATHOLOGY; RECTAL-CANCER; ENDOSCOPIC POLYPECTOMY; MULTIVARIATE-ANALYSIS; INVASIVE-CARCINOMA; PROGNOSTIC-SIGNIFICANCE; MALIGNANT POLYPS; COLONIC POLYPS AB The Cancer Committee of the College of American Pathologists has updated and expanded their protocol for the pathologic examination and reporting of specimens from patients with colorectal carcinoma, which was originally developed in 1989. The updated protocol incorporates all basic pathology data of diagnostic and prognostic significance appropriate for the treatment of patients with colorectal carcinoma. The purpose of the protocol is to serve as a basis for the development of checklists, as an outline for full narrative reporting, as a basis for research protocols, or as a guide for other types of synoptic or reporting formats. The protocol is stratified to accommodate the surgical procedures usually employed for colorectal carcinomas, including incisional endoscopic biopsy, polypectomy, local excision (transanal disc excision), and colon/colorectal resection (eg, segmental resection, total colectomy, abdominoperoneal resection). Explanatory notes detailing specific procedures and rationales for documentation of specific pathologic data are included in the protocol. The protocol uses the recently revised TNM staging system for colorectal carcinoma defined by the American Joint Committee on Cancer and the international Union Against Cancer. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Early Detect Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. St Barnabas Med Ctr, Dept Pathol, Livingston, NJ USA. Armed Forces Inst Pathol, Div Gastrointestinal Pathol, Washington, DC 20306 USA. Michigan State Univ, Coll Human Med, Dept Pathol, E Lansing, MI 48824 USA. RP Bowman, HE (reprint author), Coll Amer Pathol, 325 Waukegen Rd, Northfield, IL 60093 USA. NR 71 TC 21 Z9 21 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1997 VL 121 IS 12 BP 1247 EP 1254 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YP012 UT WOS:000071232400007 PM 9431313 ER PT J AU Yesalis, CE Barsukiewicz, CK Kopstein, AN Bahrke, MS AF Yesalis, CE Barsukiewicz, CK Kopstein, AN Bahrke, MS TI Trends in anabolic-androgenic steroid use among adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HIGH-SCHOOL-STUDENTS; UNITED-STATES; PREVALENCE; PREVENTION; INTERVENTION; PROGRAM; ABUSE AB Objective: To examine the trends in anabolic steroid use among adolescents in the United States between 1988 and 1996. Design: Computerized and manual literature searches were performed, and the resultant local, state, and national cross-sectional surveys of illicit anabolic steroid use by adolescents were reviewed. Trends in steroid use were evaluated using state and national studies administered in multiple periods. Various sampling procedures were employed, and all surveys used anonymous questionnaires. The national studies used for this analysis included the Monitoring the Future (MTF) study, the national com ponent of the Youth Risk and Behavior Surveillance System, and the National Household Survey on Drug Abuse. Setting: Most of the surveys described were self-administered in school classrooms. The National Household Survey on Drug Abuse was administered in the respondent's home. Participants: Most survey respondents were junior high and high school male and female students aged 12 to 18 years. Results: Individual state studies (i.e, a single point in time) provide evidence of continued steroid use throughout the United States despite educational and legal interventions. The findings of multiyear state-level studies show a decrease in lifetime steroid use rates between 1988 and 1994 for male and female adolescents, although no tests of statistical significance were conducted. At the national level, a significant decline (P<.01) in lifetime steroid use has taken place from 1989 to 1996 for male and female students (MTF data). However, since 1991, lifetime steroid use by male students, as measured by 2 of the 3 national surveys, has been generally stable. The third survey, MTF, shows a significant decrease (P<.05) in use from 1991 to 1996. Likewise, from 1991-1996 use of anabolic steroids during the past year (MTF data) was stable for 10th and 12th grade males; use among eighth grade males decreased significantly (P<.01). Since 1991, data from the 3 national surveys indicate an increase in lifetime anabolic steroid use among adolescent females, although only 1 of these increases is statistically significant. Furthermore, past year use of steroids (MTF data) increased for females in the 8th (P<.05), 10th (P<.05), and 12th (ns) grades. Conclusions: A long-term comparison of anabolic steroid use (from 1989-1996) indicates that use among adolescent males and females has decreased significantly (P<.05). However, for females the low point in lifetime steroid use was reached in 1991, with subsequent significant (P<.05) increases in use being reported in several national data sets. For adolescent males, after declining sharply between 1989 and 1991, steroid use has generally been stable since 1991. Moreover, based on the 1995 estimates of high school students and Youth Risk and Behavior Surveillance System data, approximately 375000 adolescent males and 175000 adolescent females in public and private schools in the United States used anabolic steroids at least once in their lives. These results suggest that prevention, intervention, and regulatory efforts to reduce steroid use at the local, state, and national levels should be reassessed, especially those efforts that focus on adolescent female steroid use. C1 PENN STATE UNIV, DEPT KINESIOL, UNIVERSITY PK, PA 16802 USA. NIDA, DIV EPIDEMIOL & PREVENT RES, ROCKVILLE, MD USA. HUMAN KINET PUBLISHERS INC, CHAMPAIGN, IL USA. RP Yesalis, CE (reprint author), PENN STATE UNIV, DEPT HLTH POLICY & ADM, 115 HENDERSON BLDG, UNIVERSITY PK, PA 16802 USA. NR 72 TC 88 Z9 90 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 EI 1538-3628 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 1997 VL 151 IS 12 BP 1197 EP 1206 PG 10 WC Pediatrics SC Pediatrics GA YL183 UT WOS:A1997YL18300005 PM 9412594 ER PT J AU Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Edwards, BK Huttunen, JK AF Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Edwards, BK Huttunen, JK TI Effect of alpha-tocopherol (vitamin E) and beta-carotene supplementation on the incidence of intermittent claudication in male smokers SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE intermittent claudication; prevention; vitamin E; alpha-tocopherol; antioxidants ID LOW-DENSITY-LIPOPROTEIN; PERIPHERAL ARTERIAL-DISEASE; CARDIOVASCULAR-DISEASE; OXIDATIVE MODIFICATION; CIGARETTE-SMOKING; CONTROLLED TRIAL; IN-VITRO; ANTIOXIDANT; LDL; SUSCEPTIBILITY AB We examined the primary preventive effect of vitamin E (alpha-tocopherol) and beta-carotene supplementation on intermittent claudication. The subjects-participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study-were male smokers aged 50 to 69 years who were randomly assigned to receive 50 mg of alpha-tocopherol daily, 20 mg of beta-carotene daily, both, or placebo. At baseline, there were 26289 men with no history or symptoms of intermittent claudication. The Rose questionnaire on intermittent claudication was administered annually to discover incident cases. We observed 2704 cases of first occurrence of typical intermittent claudication during a median follow-up time of 4.0 years. Compared with placebo, the adjusted relative risk for typical intermittent claudication among those who received alpha-tocopherol those who received alpha-tocopherol and beta-carotene, 1.02 (0.91-1.13); and among those who received beta-carotene only, 1.02 (0.92-1.14). When we compared the alpha-tocopherol-supple mented subjects with those who received no alpha-tocopherol, the adjusted relative risk for typical intermittent claudication was 1.05 (0.98-1.14), and for beta-carotene-supplemented subjects compared with those who did not receive beta-carotene, the relative risk was 0.96 (0.89-1.04). In conclusion, no primary preventive effect on intermittent claudication was observed among middle-aged male smokers who were supplemented with alpha-tocopherol, beta-carotene, or both. C1 Natl Publ Hlth Inst, Dept Nutr, ATBC Study, SF-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), Natl Publ Hlth Inst, Dept Nutr, ATBC Study, Mannerheimintie 166, SF-00300 Helsinki, Finland. EM markareetta.tornwall@ktl.fi RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N0I-CN-45165] NR 36 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 1997 VL 17 IS 12 BP 3475 EP 3480 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YZ025 UT WOS:000072212600015 PM 9437195 ER PT J AU Correia, LCL Atalar, E Kelemen, MD Ocali, O Hutchins, GM Fleg, JL Gerstenblith, G Zerhouni, EA Lima, JAC AF Correia, LCL Atalar, E Kelemen, MD Ocali, O Hutchins, GM Fleg, JL Gerstenblith, G Zerhouni, EA Lima, JAC TI Intravascular magnetic resonance imaging of aortic atherosclerotic plaque composition SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE intravascular magnetic resonance imaging; atherosclerotic plaque; human aorta ID CORONARY-ARTERY DISEASE; HUMAN-HEART; ANGIOGRAPHY; MRI; CALCIFICATION; COIL; ANGIOPLASTY; MECHANISMS; MORPHOLOGY; LUMEN AB Magnetic resonance imaging (MRI) may be an excellent tool to define atherosclerotic plaque composition, but surface MRI (SMRI) suffers from a low signal-to-noise ratio and low resolution of arterial images. Intravascular MRI (IVMRI) represents a potential solution for acquiring high-quality in vivo images of atherosclerotic plaques. Isolated segments of 11 thoracic human aortas obtained at autopsy were imaged by IVMRI using an intravascular receiver catheter coil designed and built at our institution. Images obtained by IVMRI were compared with corresponding images obtained by SMRI and with histopathological aortic cross sections. The intensity of intimal thickness and plaque components was graded by IVMRI and histopathology using a score of 1 for mild 2 for moderate, and 3 for severe intensity. IVMRI had an agreement of 75% with histopathology in fibrous cap grading (37.5% expected, kappa=0.60, P<0.001) and of 74% in necrotic core grading (39% expected, kappa=0.57, P<0.001). Intraplaque calcification was correctly graded by IVMRI in six of the eight plaques in which histopathology recognized calcium. The analysis of intimal thickness showed 80% agreement between IVMRI and histopathology (52% expected, kappa=0.59, P<0.001). IVMRI image features were similar to those of SMRI. In addition, NMRI accurately determined atherosclerotic plaque size in comparison with histopathology and SMRI (slope=1.25 cm(2), r=0.99, P<0.001 for luminal area by IVMRI vs histopathology; slope=0.97 cm(2), r=0.996, P<0.001 for luminal area by IVMRI vs SMRI). IVMRI has the potential to provide important prognostic information in patients with atherosclerosis because of its ability to accurately assess both plaque composition and size. C1 Johns Hopkins Sch Med, Dept Med, Div Cardiol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Radiol, Div Diagnost Imaging, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. RP Lima, JAC (reprint author), Johns Hopkins Hosp, Div Cardiol, Blalock 569,600 N Wolfe St, Baltimore, MD 21287 USA. RI Atalar, Ergin/D-3184-2012 OI Atalar, Ergin/0000-0002-6874-6103 FU NHLBI NIH HHS [R01-HL-43722] NR 31 TC 61 Z9 62 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 1997 VL 17 IS 12 BP 3626 EP 3632 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YZ025 UT WOS:000072212600034 PM 9437214 ER PT J AU Brady, RO AF Brady, RO TI Gaucher's disease: past, present and future SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article DE glucocerebroside; glucocerebrosidase; sphingolipid; genetic counselling; enzyme replacement therapy; gene therapy ID ENZYME REPLACEMENT THERAPY; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; PLACENTAL BETA-GLUCOCEREBROSIDASE; MEDIATED GENE-TRANSFER; PURIFIED GLUCOCEREBROSIDASE; DEFICIENCY; CELLS; EXPRESSION; RESPONSES; EFFICACY AB A patient with what is now known as Gaucher's disease was first described by P. C. E. Gaucher in 1882. Fifty years later, Aghion reported that patients with this condition accumulated a sphingoglycolipid called glucocerebroside. Considerably more time was required for the demonstration by Brady and co-workers in 1964 that Gaucher's disease was due to reduced activity of a beta-glucosidase called glucocerebrosidase. This information provided the basis for the development of reliable diagnostic tests, detection of most of the carriers of this disorder and the prenatal diagnosis of this condition. Evidence was presented in 1990 and 1991 indicating the highly beneficial effects of enzyme replacement therapy in patients with Gaucher's disease. Gene therapy for Gaucher's disease was initiated in 1995. While little indication of success was obtained in this inaugural attempt, it is expected that improvements in this technology will provide a permanent cure for patients with this disorder. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20852 USA. RP Brady, RO (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D04,10 Ctr Dr MSC 1260, Bethesda, MD 20852 USA. NR 62 TC 41 Z9 44 U1 1 U2 5 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD DEC PY 1997 VL 10 IS 4 BP 621 EP 634 DI 10.1016/S0950-3536(97)80031-5 PG 14 WC Hematology SC Hematology GA YT771 UT WOS:000071643400002 PM 9497855 ER PT J AU Erikson, A Bembi, B Schiffmann, R AF Erikson, A Bembi, B Schiffmann, R TI Neuronopathic forms of Gaucher's disease SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article DE brain; child; glucosylceramidase; administration; glucosyceramide; enzymes therapeutic use; treatment outcome; Gaucher's disease; therapy; mutation; bone marrow transplantation ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC-CELLS; PARTIAL SPLENECTOMY; ENZYME DEFICIENCY; NORRBOTTNIAN TYPE; THERAPY; GLUCOCEREBROSIDASE; INFANTILE; GENE; GENOTYPE AB Neuronopathic Gaucher patients may have a wide variety of clinical manifestations and natural history, and can present with a range of degrees of severity of systemic disease and neurological deficit. The brain pathology of these patients has been well described, but the mechanism by which glucocerebrosidase deficiency leads to neuronal dysfunction is not yet understood. The almost 20 different mutations of the glucocerebrosidase gene that have been described in Type 2 and 3 Gaucher patients poorly predict the phenotype of individual patients. Enzyme replacement therapy (ERT), often at high doses, has been shown to reverse most of the systemic manifestations of this disease, but can rarely reverse the neurological deficits. Therefore, other forms of treatment, such as gene therapy or a more efficient and direct enzyme delivery to neurons, are being devised. C1 Umea Univ, Dept Paediat, S-90185 Umea, Sweden. Ist Ricovero & Cura & Carattere Sci Burlo Garofol, I-34137 Trieste, Italy. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Erikson, A (reprint author), Umea Univ, Dept Paediat, S-90185 Umea, Sweden. NR 46 TC 50 Z9 50 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD DEC PY 1997 VL 10 IS 4 BP 711 EP 723 DI 10.1016/S0950-3536(97)80035-2 PG 13 WC Hematology SC Hematology GA YT771 UT WOS:000071643400006 PM 9497859 ER PT J AU Sidransky, E Ginns, EI AF Sidransky, E Ginns, EI TI Gaucher's disease: the best laid schemes of mice and men SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article DE Gaucher's disease; glucocerebrosidase; murine; knockout models; epidermal; metaxin ID BETA-GLUCOCEREBROSIDASE DEFICIENCY; HYDROPS-FETALIS; CONGENITAL ICHTHYOSIS; TARGETED DISRUPTION; UNIQUE GENOTYPE; MOUSE MODEL; FUSION GENE; TYPE-2; PSEUDOGENE; ABNORMALITIES AB The creation of animal models of Gaucher's disease, the inherited deficiency of the enzyme glucocerebrosidase, has led to new clinical insights and to a new appreciation of the complexity of the glucocerebrosidase gene locus. Murine embryonic stem cells with targeted modifications in the glucocerebrosidase gene were used to generate mouse models of Gaucher's disease, the first having a null glucocerebrosidase allele, The resulting knockout mice have no glucocerebrosidase activity and die within 12 hours of birth. Ultrastructural studies of liver, spleen, brain and bone marrow demonstrate the characteristic storage material seen in Gaucher patients. In the nervous system, storage of lipid increased in a rostral-caudal distribution. Analysis of skin from the knockout mice revealed histological, ultrastructural and biochemical abnormalities, The null allele Gaucher mice are analogous to neonates with Type 2 Gaucher's disease who present with hydrops foetalis and/or congenital ichthyosis. Moreover, the epidermal changes seen in Type 2 mice are also found in Type 2 patients and may provide a means to presymptomatically discriminate Type 2 from Type 1 and 3 Gaucher's disease. Another targeted modification in the murine glucocerebrosidase gene locus led to the discovery of a contiguous gene, metaxin, Closer analysis of the glucocerebrosidase gene locus, including sequencing of 75 kb of genomic DNA, reveals that this is a gene-rich region coding for seven genes and two pseudogenes. Further study of these closely arrayed genes may contribute to our understanding of the clinical variation encountered among patients with Gaucher's disease. C1 NIMH, Clin Genet Unit, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Genet Unit, Clin Neurosci Branch, NIH, Bldg 49,Room B1EE16,49 Convent Dr MSC 4405, Bethesda, MD 20892 USA. NR 60 TC 8 Z9 8 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD DEC PY 1997 VL 10 IS 4 BP 725 EP 737 DI 10.1016/S0950-3536(97)80036-4 PG 13 WC Hematology SC Hematology GA YT771 UT WOS:000071643400007 PM 9497860 ER PT J AU Niederehe, G AF Niederehe, G TI Future directions for clinical research in mental health and aging SO BEHAVIOR THERAPY LA English DT Article RP Niederehe, G (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,ROOM 18-101,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD WIN PY 1997 VL 28 IS 1 BP 101 EP 108 DI 10.1016/S0005-7894(97)80036-6 PG 8 WC Psychology, Clinical SC Psychology GA XM639 UT WOS:A1997XM63900007 ER PT J AU Panlilio, LV Schindler, CW AF Panlilio, LV Schindler, CW TI Conditioned locomotor-activating and reinforcing effects of discrete stimuli paired with intraperitoneal cocaine SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cocaine; conditioned drug effects; conditioned reinforcement; incentive-motivation; locomotor activity; rat; sensitization ID SELECTIVE ASSOCIATIONS; MESOLIMBIC DOPAMINE; SENSITIZATION; AMPHETAMINE; RATS; ATTENTION AB Studies of conditioned locomotor activity typically use an entire environmental context as the conditioned stimulus. To determine whether conditioned locomotion can be elicited by specific, discrete stimuli similar to those used in traditional studies of classical conditioning, rats were injected intraperitoneally (i.p.) with saline before 30 min sessions in a locomotor activity chamber. Interspersed (one to two times a week) with these baseline sessions, the rats were injected with cocaine (20 mg/kg) and placed in the chamber with a tone or flashing light present. Although baseline levels of activity remained stable, locomotion increased (sensitized) over six drug-stimulus pairings. Conditioned locomotor activity was elicited when the stimuli were then presented in the absence of cocaine. When a cocaine challenge was administered, locomotor activity was higher in the presence of the conditioned stimuli than in their absence, indicating that conditioning contributed to sensitization. These conditioned effects did not occur in control groups in which cocaine was not associated with the stimulus. To determine whether reinforcing properties had been conditioned to the stimuli, the rats were then tested in an operant chamber where responding in one nose-poke hole produced a 2 s conditioned-stimulus presentation. Rats that had received stimulus-drug pairings responded at a higher rate in this hole than in another, inactive hole. Locomotor activity can thus be conditioned to discrete stimuli, and the reinforcing properties conditioned to these stimuli can transfer to other environments. In this respect, the drug-conditioning effects seen in rodents appear to be analogous to the conditioned responses observed when human drug abusers are presented with discrete, drug-related stimuli. C1 NIDA, Preclin Pharmacol Lab, Behav Pharmacol & Genet Sect, NIH,Div Intramural Res, Baltimore, MD 21244 USA. RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Lab, Behav Pharmacol & Genet Sect, NIH,Div Intramural Res, POB 5180, Baltimore, MD 21244 USA. NR 34 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD DEC PY 1997 VL 8 IS 8 BP 691 EP 698 DI 10.1097/00008877-199712000-00003 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA YQ196 UT WOS:000071359400003 PM 9832954 ER PT J AU Sorbara, LR DaviesHill, TM KoehlerStec, EM Vannucci, SJ Horne, MK Simpson, IA AF Sorbara, LR DaviesHill, TM KoehlerStec, EM Vannucci, SJ Horne, MK Simpson, IA TI Thrombin-induced translocation of GLUT3 glucose transporters in human platelets SO BIOCHEMICAL JOURNAL LA English DT Article ID RAT ADIPOSE-CELLS; ENERGY-METABOLISM; EXPRESSION; BRAIN; INSULIN; PROTEINS; NEURONS; ISOFORM; STAUROSPORINE; PHOTOLABEL AB Platelets derive most of their energy from anaerobic glycolysis; during activation this requirement rises approx. 3-fold. To accommodate the high glucose flux, platelets express extremely high concentrations (155+/-18 pmol/mg of membrane protein) of the most active glucose transporter isoform, GLUT3. Thrombin, a potent platelet activator, was found to stimulate 2-deoxyglucose transport activity 3-5-fold within 10 min at 25 degrees C, with a half-time of 1-2 min. To determine the mechanism underlying the increase in glucose transport activity, an impermeant photolabel, [2-H-3]2N-4-(1-azi-2,2,2-trifluoethyl)benzoy1-1,3,-bis-(D-mannose-4-ylozy)-2-propylamine, was used to covalently bind glucose transporters accessible to the extracellular milieu. In response to thrombin, the level of transporter labelling increased 2.7-fold with a half-time of 1-2 min. This suggests a translocation of GLUT3 transporters from an intracellular site to the plasma membrane in a manner analogous to that seen for the translocation of GLUT4 in insulin-stimulated rat adipose cells. To investigate whether a similar signalling pathway was involved in both systems, platelets and adipose cells were exposed to staurosporin and wortmannin, two inhibitors of GLUT4 translocation in adipose cells. Thrombin stimulation of glucose transport activity in platelets was more sensitive to staurosporin inhibition than was insulin-stimulated transport activity in adipose cells, but it was totally insensitive to wortmannin. This indicates that the GLUT3 translocation in platelets is mediated by a protein kinase C not by a phosphatidylinositol 3-kinase mechanism. In support of this contention, the phorbol ester PMA, which specifically activates protein kinase C, fully stimulated glucose transport activity in platelets and was equally sensitive to inhibition by staurosporin. This study provides a cellular mechanism by which platelets enhance their capacity to import glucose to fulfil the increased energy demands associated with activation. C1 NIDDK,NIH,EDMNS,DB,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PEDIAT,HERSHEY,PA 17033. CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 38 TC 24 Z9 25 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1997 VL 328 BP 511 EP 516 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL009 UT WOS:A1997YL00900025 PM 9371709 ER PT J AU Rota, C Barr, DP Martin, MV Guengerich, FP Tomasi, A Mason, RP AF Rota, C Barr, DP Martin, MV Guengerich, FP Tomasi, A Mason, RP TI Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide SO BIOCHEMICAL JOURNAL LA English DT Article ID UNSATURATED FATTY-ACIDS; O-O BOND; CUMENE HYDROPEROXIDE; LIPID-PEROXIDATION; SOYBEAN LIPOXYGENASE-1; MEDIATED INACTIVATION; REDUCTIVE CLEAVAGE; HYDROGEN-PEROXIDE; ALKOXYL RADICALS; AQUEOUS-SOLUTION AB The ESR spin-trapping technique was employed to investigate the reaction of rabbit cytochrome P-450 1A2 (P450) with linoleic acid hydroperoxide. This system was compared with chemical systems where FeSO4 or FeCl3 was used in place of P450. The spin trap 5,5'-dimethyl-1-pyrroline N-oxide (DMPO) Was employed to detect and identify radical species. The DMPO adducts of hydroxyl, O-2(-.), peroxyl, methyl and acyl radicals were detected in the P450 system. The reaction did not require NADPH-cytochrome P-450 reductase or NADPH. The same DMPO-radical adducts were detected in the FeSO4 system. Only DMPO-(OH)-O-. radical adduct and carbon-centred radical adducts were detected in the FeCl3 system. Peroxyl radical production was completely O-2-dependent. We propose that polyunsaturated fatty acids are initially reduced to form alkoxyl radicals, which then undergo intramolecular rearrangement to form epoxyalkyl radicals. Each epoxyalkyl radical reacts with O-2, forming a peroxyl radical. Subsequent unimolecular decomposition of this peroxyl radical eliminates O-2(-.) radical. C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CTR MOL TOXICOL,NASHVILLE,TN 37232. RP Rota, C (reprint author), UNIV MODENA,DEPT BIOMED SCI,VIA CAMPI 276,I-41100 MODENA,ITALY. OI Tomasi, Aldo/0000-0002-1356-3430 NR 56 TC 50 Z9 51 U1 1 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1997 VL 328 BP 565 EP 571 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL009 UT WOS:A1997YL00900032 PM 9371716 ER PT J AU Barry, CE AF Barry, CE TI New horizons in the treatment of tuberculosis SO BIOCHEMICAL PHARMACOLOGY LA English DT Editorial Material DE tuberculosis; drug resistance; isoniazid; pyrazinamide; ethambutol; methyltransferase ID MYCOBACTERIAL CELL-WALL; PYRAZINOIC ACID-ESTERS; VITRO ANTIMYCOBACTERIAL ACTIVITY; OXIDATIVE-STRESS-RESPONSE; CATALASE-PEROXIDASE GENE; ISONIAZID RESISTANCE; MYCOLIC ACIDS; RIFAMPICIN-RESISTANCE; ARABINAN BIOSYNTHESIS; TUBERCLE BACILLUS AB The development of new chemotherapy for the treatment of tuberculosis has three major objectives: first, the development of faster-acting drugs to shorten the duration of treatment; second, the development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies; and, third, the development of chemotherapeutics that specifically target dormant bacilli to treat the one-third of the world's population latently infected with tubercle bacilli. Strategies based upon optimizing the inhibition of known targets require an extensive knowledge of the detailed mechanism of action of current antimycobacterial agents. For many agents such as isoniazid, ethambutol, rifampin, and pyrazinamide such knowledge is now available. Strategies based upon the identification of novel targets will necessitate the identification of biochemical pathways specific to mycobacteria and related organisms. Many unique metabolic processes occur during the biosynthesis of mycobacterial cell wall components, and some attractive new targets have emerged. The development of targets specific to latency will require a detailed picture of the metabolism and biochemical pathways occurring in dormant bacilli. Recent evidence suggests that anaerobic metabolic pathways may operate in dormant bacilli, and the enzymes involved in such pathways may also provide significant new targets for intervention. The combination of the mycobacterial genome sequence that is anticipated to become available this year with an improved understanding of the unique metabolic processes that define mycobacteria asa genus offers the greatest hope for the elimination of one of mankind's oldest enemies. (C) 1997 Elsevier Science Inc. RP Barry, CE (reprint author), NIAID,ROCKY MT LABS,TB RES UNIT,INTRACELLULAR PARASITES LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-15] NR 84 TC 59 Z9 61 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 DEC 1 PY 1997 VL 54 IS 11 BP 1165 EP 1172 DI 10.1016/S0006-2952(97)00163-9 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF867 UT WOS:A1997YF86700001 PM 9416967 ER PT J AU Nelson, TJ Alkon, DL AF Nelson, TJ Alkon, DL TI Biochemistry of molluscan learning and memory SO BIOESSAYS LA English DT Review ID PROTEIN-KINASE-C; LONG-TERM SENSITIZATION; ELEMENT-BINDING PROTEIN; INTRACELLULAR CALCIUM; SYNAPTIC PLASTICITY; NERVOUS-SYSTEM; K+ CHANNELS; APLYSIA; FACILITATION; HERMISSENDA AB Studies of learning in marine invertebrates have yielded new information, implicating protein kinase C and calmodulin-dependent protein kinase as critical components in pathways for learning and memory that are shared with higher vertebrates. Recent advances correlating in vitro biochemical and biophysical measurements with in vivo learning have begun to elaborate the roles in memory storage for these two kinases, their substrates, and signaling proteins such as calexcitin and calmodulin. Other studies have implicated transcription factors associated with kinases such as the cyclic AMP response element binding protein (CREB), These experiments have resulted in a greater understanding of the role of second messengers, principally calcium and cyclic AMP (cAMP), as vehicles for transforming memory-specific effects occurring at the membrane into permanent DNA-mediated cellular and structural changes. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Nelson, TJ (reprint author), NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. NR 69 TC 6 Z9 6 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD DEC PY 1997 VL 19 IS 12 BP 1045 EP 1053 DI 10.1002/bies.950191203 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA YM278 UT WOS:000071047600002 ER PT J AU George, DT Lindquist, T Ragan, PW Alim, T Eckardt, MJ Linnoila, M AF George, DT Lindquist, T Ragan, PW Alim, T Eckardt, MJ Linnoila, M TI Effect of alcoholism on the incidence of lactate-induced panic attacks SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; alcohol withdrawal; panic; comorbidity; lactate; adenosine triphosphate-gated K+ channels ID SENSITIVE K+ CHANNELS; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; SODIUM LACTATE; BINDING-SITES; AGORAPHOBIA; DEPRESSION; DEPENDENCE; SULFONYLUREAS; LOCALIZATION AB Background: Chronic alcohol use is associated with higher than expected rates of panic disorder, Methods: To study the relationship between alcoholism and panic disorder, we administered the panicogenic agent, sodium lactate, to 26 alcoholics with either panic disorder or frequent panic attacks (ALCPAN), 20 nonalcoholics with panic disorder (PAN), 14 alcoholics without a history of panic attacks, and 14 healthy volunteers. Results: PAN were significantly more likely to have a lactate-induced panic attack (65%) than ALCPAN (23%). ALCPAN who had the onset of panic attacks prior to alcoholism also had a reduced frequency of lactate-induced panic attacks (26.7%) compared to PAN, Conclusions: There is a reduced incidence of lactate-induced panic attacks in ALCPAN. This reduction does not appear to be explained by the relative onset of panic attacks to alcoholism. The role of excessive alcohol consumption in the decreased frequency of lactate-induced panic attacks seen in ALCPAN needs further study. Published 1997 Society of Biological Psychiatry. C1 ST ELIZABETH ACUTE PSYCHIAT HOSP,WASHINGTON,DC. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RP George, DT (reprint author), NIAAA,CLIN STUDIES LAB,DICBR,ROOM 6S-240,10 CTR DR MSC-1610,BETHESDA,MD 20892, USA. NR 36 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 1997 VL 42 IS 11 BP 992 EP 999 DI 10.1016/S0006-3223(97)00008-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YF328 UT WOS:A1997YF32800004 PM 9386850 ER PT J AU Nam, J AF Nam, J TI Establishing equivalence of two treatments and sample size requirements in matched-pairs design SO BIOMETRICS LA English DT Article DE efficiency of matching; equivalence tests; individually matched pairs; type I error probability; sample size ID NULL HYPOTHESIS; CLINICAL-TRIALS; MCNEMARS TEST; DISTRIBUTIONS; STATISTICS; CRITERIA; POWER AB Statistical methods for testing the null hypothesis of a nonzero difference between two treatments and the sample size determination for matched-pairs studies are investigated. A Wald-type test proposed by Lu and Bean (1995, Statistics in Medicine 14, 1831-1839) is anticonservative, i.e., its false positive error rate is greater than specified. Score method and normal deviate based on a restricted maximum likelihood estimation are presented. These two test statistics are shown to be algebraically equal. Their actual type I error probabilities are satisfactorily close to a nominal level. Numerical examinations demonstrate that the sample size formulas using these alternative methods are reasonable while that by Lu and Bean is not. The efficiency of matching in equivalence studies is positively related to intercorrelation or the kappa coefficient of agreements. We recommend the score or hit methods to establish equivalence of two treatments for individually matched samples. C1 NCI, Biostat Branch, Rockville, MD 20892 USA. RP Nam, J (reprint author), NCI, Biostat Branch, Execut Plaza N,Room 403,6130 Execut Blvd,MSC 7368, Rockville, MD 20892 USA. NR 24 TC 75 Z9 77 U1 3 U2 9 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1997 VL 53 IS 4 BP 1422 EP 1430 DI 10.2307/2533508 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA YN246 UT WOS:000071147700020 PM 9423257 ER PT J AU Carroll, RJ Freedman, L Pee, D AF Carroll, RJ Freedman, L Pee, D TI Design aspects of calibration studies in nutrition, with analysis of missing data in linear measurement error SO BIOMETRICS LA English DT Article DE errors-in-variables; estimating equations; linear regression; maximum likelihood; measurement error; method of moments; missing data; model robustness; nutrition; sampling designs; semiparametrics; stratified sampling; weighting ID WOMENS HEALTH TRIAL; BREAST-CANCER; MODELS; DIET; COHORT; FAT AB Motivated by an example in nutritional epidemiology; we investigate some design and analysis aspects of linear measurement error models with missing surrogate data, The specific problem investigated consists of an initial large sample in which the response (a food frequency questionnaire, FFQ) is observed and then a smaller calibration study in which replicates of the error prone predictor are observed (food records or recalls, FR). The difference between our analysis and most of the measurement error model literature is that, in our study, the selection into the calibration study can depend on the value of the response. Rationale for this type of design is given. Two major problems are investigated. In the design of a calibration study, one has the option of larger sample sizes and fea er replicates or smaller sample sizes and more replicates. Somewhat surprisingly. neither strategy is uniformly preferable in cases of practical interest. The answers depend on the instrument used (recalls or records) and the parameters of interest. The second problem investigated is one of analysis. In the usual linear model with no missing data, method of moments; estimates and normal-theory maximum likelihood estimates are approximately equivalent, with the former method in most use because it can be calculated easily and explicitly. Both estimates are valid without any distributional assumptions. In contrast, in the missing data problem under consideration, only the moments estimate is distribution-free, but the maximum likelihood estimate has at least 50% greater precision in practical situations when normality obtains. Implications for the design of nutritional calibration studies are discussed. C1 Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, DCPC, Biometry Branch, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. RP Carroll, RJ (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. FU NCI NIH HHS [CA-57030] NR 27 TC 18 Z9 21 U1 0 U2 7 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1997 VL 53 IS 4 BP 1440 EP 1457 DI 10.2307/2533510 PG 18 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA YN246 UT WOS:000071147700022 PM 9423259 ER PT J AU Shi, Q Verdier-Pinard, P Brossi, A Hamel, E Lee, KH AF Shi, Q Verdier-Pinard, P Brossi, A Hamel, E Lee, KH TI Antitumor agents - CLXXV. Anti-tubulin action of (+)-thiocolchicine prepared by partial synthesis SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE colchicine; thiocolchicine; enantiomer; antitumor; antitubulin ID THIOCOLCHICINE; COLCHICINOIDS; ANALOGS; RING AB (+)-Thiocolchicine (2b) was prepared from (+/-)-colchicine (1) in a five-step reaction sequence that included chromatographic separation of appropriate camphanylated diastereomers. Acid hydrolysis of the (+)-diastereomer, followed by acetylation, yielded the desired product 2b. (+)-Thiocolchicine has 15-fold lower inhibitory activity against tubulin polymerization than (-)-thiocolchicine, and is 29-fold less potent for inhibiting growth of human Burkitt lymphoma cells. The enantiomer 2a, prepared from the (-)-camphanylated diastereomer, had potent activity in all assays comparable to that of (-)-thiocolchicine prepared by other methods. These results support the hypothesis that the proper configuration of colchicine-related compounds is an important requirement for their anti-tubulin action. (C) 1997 Elsevier Science Ltd. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI,Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment Diagnosis & Ctr, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. OI Verdier-Pinard, Pascal/0000-0002-6149-6578 FU NCI NIH HHS [CA 17625, CA 54508] NR 15 TC 15 Z9 16 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC PY 1997 VL 5 IS 12 BP 2277 EP 2282 DI 10.1016/S0968-0896(97)00171-5 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA YQ970 UT WOS:000071443500018 PM 9459025 ER PT J AU Iwasa, KH AF Iwasa, KH TI Current noise spectrum and capacitance due to the membrane motor of the outer hair cell: Theory SO BIOPHYSICAL JOURNAL LA English DT Article ID GUINEA-PIG COCHLEA; MOTILITY; CHARGE AB The voltage-dependent motility of the outer hair cell is based on a membrane motor densely distributed in the lateral membrane. The gating charge of the membrane motor is manifested as a belt-shaped membrane potential dependence of the membrane capacitance. In this paper it is shown that movements of the gating charge should produce a high-pass current noise described by an inverse Lorentzian similar to the one shown by Kolb and Lauger for ion carriers. The frequency dependence of the voltage-dependent capacitance is also derived. These derivations are based on membrane motor models with two or three states. These two models lead to similar predictions on the capacitance and current noise. It is expected that the examination of the spectral properties of these quantities would be a useful means of determining the relaxation time for conformational transitions of the membrane motor. RP Iwasa, KH (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS, BIOPHYS SECT,CELL BIOL LAB,NIH,BLDG 9, RM 1E120, BETHESDA, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 27 TC 15 Z9 15 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 DEC PY 1997 VL 73 IS 6 BP 2965 EP 2971 PG 7 WC Biophysics SC Biophysics GA YJ673 UT WOS:A1997YJ67300011 PM 9414211 ER PT J AU Driscoll, SL Hawkins, ME Balis, FM Pfleiderer, W Laws, WR AF Driscoll, SL Hawkins, ME Balis, FM Pfleiderer, W Laws, WR TI Fluorescence properties of a new guanosine analog incorporated into small oligonucleotides SO BIOPHYSICAL JOURNAL LA English DT Article ID DYNAMICS; DNA; PROTEINS AB The fluorescence properties of 3-methyl-isoxanthopterin (3-MI) incorporated into different oligonucleotides have been determined. This highly fluorescent guanosine analog has its absorption and fluorescence spectra well resolved from those of the normal nucleotides and the aromatic amino acids. The small shifts observed in absorption and fluorescence emission spectra upon incorporation of 3-MI into these oligonucleotides are consistent with a general solvent effect and do not suggest any contribution from the position of the probe from the 5' end, the sequence of nucleotides immediately 5' or 3' to the probe, or the single-or double-stranded nature of the oligomer. However, steady-state and time-resolved fluorescence studies indicate that the presence of a purine immediately 5' or 3' to the probe results in some dynamic but mostly static quenching in the single-stranded oligomer. Furthermore, a 3' purine is more effective than a 5' purine, and an adenine appears to be more effective than a guanine for these static quenching interactions. Formation of the double-stranded oligomer leads to an additional loss of quantum yield, which can also be ascribed primarily to static quenching. These results show that this new class of spectrally enhanced fluorescent purine analogs will be able to provide useful information concerning the perturbation of nucleic acid structures. C1 CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV KONSTANZ,FAK CHEM,D-78464 CONSTANCE,GERMANY. RI Kieweg, Sarah/A-7007-2009 FU NIGMS NIH HHS [GM39750] NR 26 TC 49 Z9 50 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1997 VL 73 IS 6 BP 3277 EP 3286 PG 10 WC Biophysics SC Biophysics GA YJ673 UT WOS:A1997YJ67300038 PM 9414238 ER PT J AU Konig, S Fales, HM AF Konig, S Fales, HM TI Gradient-based automated protein folding SO BIOTECHNIQUES LA English DT Article C1 NHLBI,NIH,LBC CLIN CTR,BETHESDA,MD 20892. RI Konig, Simone/B-6504-2008 OI Konig, Simone/0000-0003-0672-7246 NR 0 TC 0 Z9 0 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 DEC PY 1997 VL 23 IS 6 BP 1010 EP & PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK461 UT WOS:A1997YK46100010 PM 9421627 ER PT J AU Chakrabarti, S Sisler, JR Moss, B AF Chakrabarti, S Sisler, JR Moss, B TI Compact, synthetic, vaccinia virus early/late promoter for protein expression SO BIOTECHNIQUES LA English DT Article ID GENE; SELECTION; VECTOR; RECOMBINANTS; POXVIRUSES; CLONING AB Vaccinia virus, a member of the poxvirus family, is widely used as a mammalian cell expression vector. Vaccinia virus replicates in the cytoplasm and has its own transcriptional system, making it necessary to use viral promoters. Here, we describe the design, construction and use of a 40-bp synthetic, vaccinia virus promoter with largely overlapping early and late regulatory elements. Convenient plasmid transfer vectors are depicted for expression of one or two genes under control of strong early/late promoters and allowing for thymidine kinase (TK) or antibiotic selection of recombinant viruses. C1 NIAID,NIH,BETHESDA,MD 20892. NR 17 TC 253 Z9 259 U1 1 U2 4 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1997 VL 23 IS 6 BP 1094 EP 1097 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK461 UT WOS:A1997YK46100026 PM 9421642 ER PT J AU Veiby, OP Borge, OJ Martensson, A Beck, EX Schade, AE Grzegorzewski, K Lyman, SD Martensson, IL Jacobsen, SEW AF Veiby, OP Borge, OJ Martensson, A Beck, EX Schade, AE Grzegorzewski, K Lyman, SD Martensson, IL Jacobsen, SEW TI Bidirectional effect of interleukin-10 on early murine B-cell development: Stimulation of flt3-ligand plus interleukin-7-dependent generation of CD19(-) ProB cells from uncommitted bone marrow progenitor cells and growth inhibition of CD19(+) ProB cells SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PRE-B; C-KIT; LYMPHOCYTES-B; FLT3 LIGAND; MAST-CELL; IN-VITRO; IL-10; MOUSE; DIFFERENTIATION AB B-cell commitment and early development from multipotent hematopoietic progenitor cells has until recently been considered to be dependent on direct interaction with stromal cells. We recently showed that the flt3 ligand (FL) has a unique ability to interact with interleukin-7 (IL-7) to directly and selectively promote B-cell development from murine bone marrow progenitor cells with a combined myeloid and lymphoid potential. Here we report that whereas IL-10 alone has no ability to stimulate growth of primitive (Lin(-)Sca-1(+)c-kit(+)) bone marrow progenitor cells, it potently enhances FL + IL-7-induced proliferation (sevenfold). This enhanced proliferation results from recruitment of progenitors unresponsive to FL + IL-7 alone, as well as from increased growth of individual clones, resulting in a 7,000-fold cellular expansion over 12 days. Single cell cultures and delayed addition studies suggested that the stimulatory effect of IL-10 was directly mediated on the progenitor cells. The cells generated in response to FL + IL-7 + IL-10 appeared to be almost exclusively proB cells, as shown by their expression of B220, CD24, CD43, and lack of expression of cp, myeloid, erythroid, and T-cell surface antigens. Although IL-10 also enhanced kit ligand (KL) + IL-7-induced proliferation of Lin(-)Sca-1(+)c-kit(+). C1 UNIV LUND HOSP,DEPT INTERNAL MED,STEM CELL LAB,S-22185 LUND,SWEDEN. LUND UNIV,DEPT CELL & MOL BIOL,IMMUNOL GRP,LUND,SWEDEN. HIPPLE CANC RES CTR,DAYTON,OH. PROGENITOR INC,COLUMBUS,OH. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. NR 48 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1997 VL 90 IS 11 BP 4321 EP 4331 PG 11 WC Hematology SC Hematology GA YH762 UT WOS:A1997YH76200010 PM 9373243 ER PT J AU Beilmann, M Odenthal, M Jung, W VandeWoude, GF Dienes, HP Schirmacher, P AF Beilmann, M Odenthal, M Jung, W VandeWoude, GF Dienes, HP Schirmacher, P TI Neoexpression of the c-met hepatocyte growth factor scatter factor receptor gene in activated monocytes SO BLOOD LA English DT Article ID LEUKEMIA-CELL-LINE; HEMATOPOIETIC PROGENITOR CELLS; FACTOR HEPATOPOIETIN-A; MYELOGENOUS LEUKEMIA; PARTIAL-HEPATECTOMY; LIVER-REGENERATION; EPITHELIAL-CELLS; TYROSINE KINASE; MESSENGER-RNA; DNA-SYNTHESIS AB Hepatocyte growth factor-scatter factor (HGF-SF) mediates mito-, moto-, and morphogenic effects through the MET receptor, a membrane bound tyrosine kinase. HGF-SF/MET signaling is mitogenic for a large number of epithelial and endothelial cells and activates organ regeneration. HGF-SF transcripts have been detected in various myeloid cell lines. Therefore, the potential role of HGF-SF/MET signaling for circulating cells of the immune system, especially under conditions of inflammation, was evaluated. Several B-lymphoid and myeloid cell lines were found to express HGF-SF or c-met transcripts, while activity of both genes was mutually exclusive with the exception of low level coexpression in two B-cell lines, HGF-SF transcripts were present in low quantities in freshly isolated peripheral blood mononuclear cells (PBMNCs). In contrast, c-met expression was not detected in freshly isolated cells from peripheral blood, but was induced in monocytes by activation of monocytic or T-cell function. HGF-SF incubation led to an increased c-fos steady state transcript level in myeloblastic K562 cells and moderately promoted cell viability of freshly isolated preactivated monocytes, c-met expression is thus established in activated monocytes, in particular under conditions resembling inflammation, making these cells accessible to functional effects of HGF-SF. (C) 1997 by The American Society of Hematology. C1 UNIV HOSP,INST PATHOL,D-55101 MAINZ,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. NR 59 TC 64 Z9 64 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 DEC 1 PY 1997 VL 90 IS 11 BP 4450 EP 4458 PG 9 WC Hematology SC Hematology GA YH762 UT WOS:A1997YH76200022 PM 9373255 ER PT J AU Weichold, FF Jiang, YZ Dunn, DE Bloom, M Malkovska, V Hensel, NF Barrett, AJ AF Weichold, FF Jiang, YZ Dunn, DE Bloom, M Malkovska, V Hensel, NF Barrett, AJ TI Regulation of a graft-versus-leukemia effect by major histocompatibility complex class II molecules on leukemia cells: HLA-DR1 expression renders K562 cell tumors resistant to adoptively transferred lymphocytes in severe combined immunodeficiency mice nonobese diabetic mice SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; CYTOTOXIC T-CELLS; HOST DISEASE; SCID MICE; RELAPSE; DEPLETION; APOPTOSIS AB To understand the role of key molecules in determining the strength and nature of allogeneic T-cell response to leukemia, We transfected HLA-DR1 into the major histocompatibility complex (MMC)-deficient, natural killer (NK)-cell sensitive K562 leukemia cell line. Untransfected K562 cells stimulated NK proliferation in vitro and formed subcutaneous tumors in severe combined immunodeficiency/non-obese diabetic (SCID/NOD) mice. Tumor growth was inhibited by adoptive intravenous transfer of fresh unprimed peripheral blood mononuclear cells (PBMC). In contrast, HLA-DR1 transfected cells stimulated CD4(+) T cells, but not NK-cell proliferation in vitro and formed tumors resistant to fresh PBMC in SCID/NOD mice, Tumors not expressing MHC were infiltrated with CD16(+)CD56(+) lymphocytes whereas nonregressing HLA-DR1 expressing tumors showed only a scanty infiltration with both T-cell and NK-cell subsets. The results indicate that MHC class II expression by leukemia cells can determine the effector cell type that it engages. In vivo MHC class II expression rendered K562 cell tumors resistant to NK-cell mediated antitumor reactivity. (C) 1997 by The American Society of Hematology. C1 NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,INST CANC,WASHINGTON,DC 20010. NR 28 TC 8 Z9 8 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 DEC 1 PY 1997 VL 90 IS 11 BP 4553 EP 4558 PG 6 WC Hematology SC Hematology GA YH762 UT WOS:A1997YH76200033 PM 9373266 ER PT J AU Ungerleider, LG AF Ungerleider, LG TI Cortical mechanisms for memory: Automatic versus voluntary processes SO BRAIN AND COGNITION LA English DT Article C1 NIMH, Rockville, MD 20857 USA. RP Ungerleider, LG (reprint author), NIMH, Rockville, MD 20857 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD DEC PY 1997 VL 35 IS 3 BP 301 EP 302 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA YU863 UT WOS:000071763600013 ER PT J AU Harbluk, JL Weingartner, HJ AF Harbluk, JL Weingartner, HJ TI Memory distortions in detoxified alcoholics SO BRAIN AND COGNITION LA English DT Article ID FALSE AB Both detoxified alcoholics and matched controls demonstrated false recall and recognition in a task previously shown to elicit memory distortions. The important results concerning memory distortions in detoxified alcoholics come from three specific findings in the recall data. Controls clearly recalled a greater proportion of targets than critical lures, while this difference was only marginally significant for alcoholics. Alcoholics also produced the critical lures earlier in their recall than controls. Finally, alcoholics produced more extralist intrusions than critical lures while the opposite was observed for the controls. These results suggest that the nature of the memory distortions differs for these two groups of subjects. The memory distortions exhibited by the alcoholics are consistent with a deficit in monitoring the source of information in memory. C1 NIH, Bethesda, MD 20892 USA. RP Harbluk, JL (reprint author), NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD DEC PY 1997 VL 35 IS 3 BP 328 EP 330 PG 3 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA YU863 UT WOS:000071763600022 ER PT J AU Marks, AR Cermak, LS AF Marks, AR Cermak, LS TI Impaired short-term memory and intact temporal memory in amnesic patients SO BRAIN AND COGNITION LA English DT Article AB The continual-distractor paradigm was used to investigate the recency effect in amnesic patients. Amnesics' recall displayed normal recency effects in lists ranging from 18 to 60 sec long. In contrast, overall recall was impaired compared to normals in all lists and across all positions, including the final position. These findings dissociate the recency effect from overall levels of recall. Performance by the controls suggests that the amnesic patients performed worse overall due to an inability to benefit from rehearsal. Current theorizing about the recency effect suggests that amnesics' normal recency effect may be evidence of an ability to encode and retrieve temporally-associated information. C1 NIH, Bethesda, MD 20892 USA. RP Marks, AR (reprint author), NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD DEC PY 1997 VL 35 IS 3 BP 423 EP 426 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA YU863 UT WOS:000071763600056 ER PT J AU Drugan, RC Basile, AS Ha, JH Healy, D Ferland, RJ AF Drugan, RC Basile, AS Ha, JH Healy, D Ferland, RJ TI Analysis of the importance of controllable versus uncontrollable stress on subsequent behavioral and physiological functioning SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE coping; triadic design; rat; learned helplessness; behavioral depression ID LEARNED HELPLESSNESS; COPING BEHAVIOR; INDUCED ANALGESIA; RATS; ESCAPE AB Original observations of the effects of stress exposure on behavioral, physiological and pathological indices were documented in the mid 1960s [J.B. Overmier, Interference with avoidance behavior: failure to avoid traumatic shock, J. Exp. Psychol. 78 (1968) 340-343 [12]; J.B. Overmier, M.E.P. Seligman, Effects of inescapable shock upon subsequent escape and avoidance learning, J. Comp. Physiol. Psychol. 63 (1967) 28-33 [13]; M.E.P. Seligman, S.F. Maier, Failure to escape traumatic shock, J. Exp. Psychol. 74 (1967) 1-9 [15]; J.M. Weiss, Effects of coping responses on stress, J. Comp. Physiol. Psychol. 65 (1968) 251-260 [18]]. Studies employing the triadic design (e.g. escapable stress, yoked-inescapable stress and no stress) indicated that the deficits following stress exposure were not caused by stress per se, rather the uncontrollability of the stress was the critical determinant. In this paradigm, the first group (escape) receives exposure to an environmental event that it can "control" by performing a behavioral response. Stress control or coping behavior includes the ability to alter the onset, duration, intensity or pattern of an aversive experience [S.F. Maier, M.E.P. Seligman, Learned helplessness: theory and evidence, J. Exp. Psychol.: Gen. 105 (1976) 3-46 [10]]. The second group is "yoked" to its escape partner and receives the identical physical stressor as its escape counterpart, but there is no behavioral response that the yoked subject can make to alter the outcome. The third group (naive) receives no stress exposure and is either restrained in the experimental apparatus or remains in the home cage until subsequent testing. Researchers using this triadic design should be aware of the concerns of certain investigators [R.M. Church, Systematic effect of random error in the yoked control design, Psychol. Bull. 62 (1964) 122-131 [3]; E.A. Wasserman, Response bias in the yoked control procedure, Behav. Brain Sci. 11 (1988) 477-478 [17]] who have raised important issues about the validity of the yoked control design because of the possibility of systematic biases. For example, individual differences in stress reactivity may result in random error in the yoked control group. This point will be addressed further in Section 5. This procedure allows the investigator to analyze the contributions of the importance of psychological dynamics of stress on a variety of dependent measures including: behavioral,pharmacological, neurochemical and immunological indices. (C) 1997 Elsevier Science B.V. C1 Univ New Hampshire, Dept Psychol, Durham, NH 03824 USA. NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med, Dept Neurosci, Rochester, NY 14642 USA. RP Drugan, RC (reprint author), Univ New Hampshire, Dept Psychol, Conant Hall,10 Lib Way, Durham, NH 03824 USA. RI Ferland, Russell/E-3500-2010; OI Ferland, Russell/0000-0002-8044-2479 FU NIMH NIH HHS [MH 45475] NR 22 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD DEC 1 PY 1997 VL 2 IS 1 BP 69 EP 74 DI 10.1016/S1385-299X(97)00031-7 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YP372 UT WOS:000071270300011 PM 9438074 ER PT J AU Parascandola, M AF Parascandola, M TI Brute science: Dilemmas of animal experimentation SO BRITISH JOURNAL FOR THE PHILOSOPHY OF SCIENCE LA English DT Book Review C1 NIH, Hist Off, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NIH, Hist Off, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0882 J9 BRIT J PHILOS SCI JI Br. J. Philos. Sci. PD DEC PY 1997 VL 48 IS 4 BP 621 EP 624 DI 10.1093/bjps/48.4.621 PG 4 WC History & Philosophy Of Science SC History & Philosophy of Science GA YM846 UT WOS:000071107400015 ER PT J AU Brown, NJ Ali, S Reed, MWR Wiltrout, R Rees, RC AF Brown, NJ Ali, S Reed, MWR Wiltrout, R Rees, RC TI Trafficking of activated lymphocytes into the RENCA tumour microcirculation in vivo in mice SO BRITISH JOURNAL OF CANCER LA English DT Article DE leucocyte/lymphocyte trafficking; tumour microcirculation; RENCA tumour; immunotherapy ID RENAL-CELL CARCINOMA; KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; BLOOD-VESSELS; IN-VIVO; MELANOMA; LABELS; IMMUNOTHERAPY; MIGRATION AB The aim of the study was to establish a model of tumour microcirculation in vivo using the murine renal cell carcinoma cell line (RENCA) implanted into the mouse cremaster muscle, and subsequently to investigate the trafficking of syngeneic lymphocyte subpopulations into both the RENCA tumour and the surrounding normal cremaster muscle microcirculation. We have demonstrated that RENCA tumour cells, at a dose of 1.5 x 10(5) per 30 mu l injected into the cremaster muscle, reproducibly produced a vascularized tumour suitable for in vivo microscopy at 10-14 days. Injection of fluorescently labelled effector cells (1 x 10(6)) including naive splenocytes, T-cell enriched populations and ex vivo interleukin 2 (IL-2)-activated splenocytes all migrated to and flowed through both the tumour and the normal microcirculation, with negligible adhesion. However, we observed the selective recruitment, localization and arrest of IL-2-activated splenocytes (P < 0.05) into the tumour microcirculation, and the subsequent extravasation of cells into the tumour intestitium in some instances. This did not occur with the other effector cells. We also observed the absence of leucocyte rolling in the tumour microcirculation, suggesting an impairment in adhesion molecule expression on the tumour endothelium. We have therefore established the potential of this model for defining further effector cell-tumour-endothelium interactions. C1 Univ Sheffield, Royal Hallamshire Hosp, Dept Surg & Anaesthet Sci, Sheffield S10 2JF, S Yorkshire, England. Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield S10 2RX, S Yorkshire, England. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. NCI, Biol Response Modifiers Programme, Frederick, MD 21701 USA. RP Brown, NJ (reprint author), Univ Sheffield, Royal Hallamshire Hosp, Dept Surg & Anaesthet Sci, Floor K,Glossop Rd, Sheffield S10 2JF, S Yorkshire, England. OI Brown, Nicola/0000-0002-2100-1905 NR 27 TC 8 Z9 8 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1997 VL 76 IS 12 BP 1572 EP 1578 DI 10.1038/bjc.1997.599 PG 7 WC Oncology SC Oncology GA YM286 UT WOS:000071048400008 PM 9413944 ER PT J AU Selleri, C Sato, T Raiola, AM Rotoli, B Young, NS Maciejewski, JP AF Selleri, C Sato, T Raiola, AM Rotoli, B Young, NS Maciejewski, JP TI Induction of nitric oxide synthase is involved in the mechanism of Fas-mediated apoptosis in haemopoietic cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE iNOS; Fas-R; CML; NO; apoptosis ID NECROSIS-FACTOR-ALPHA; INTERFERON REGULATORY FACTOR-1; L-ARGININE; IN-VITRO; HEMATOPOIETIC INHIBITION; INSULIN-SECRETION; DNA-DAMAGE; TNF-ALPHA; GAMMA; EXPRESSION AB Induction of nitric oxide synthase (iNOS) and production of the toxic metabolite nitric oxide (NO) is one of the interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) regulated effector mechanisms that can lead to apoptosis of haemopoietic progenitor cells. Fas-receptor (Fas-R) expression can be stimulated by IFN-gamma and TNF-alpha. Transactivation of iNOS, and possibly Fas-R promoters, by interferon regulatory factor-1 expressed in response to IFN-gamma may be a part of the iNOS transduction pathway We investigated whether the effects of Fas-R triggering in haemopoietic cells were mediated by NO. On Western blotting, we observed that Fas-receptor agonist, monoclonal antibody CH11, enhanced expression of iNOS, As shown by the reverse transcription polymerase chain reaction, CH11 also induced iNOS mRNA expression in purified CD34(+) cells. To determine whether NO was involved in Fas-mediated apoptosis we inhibited iNOS-catalysed production of NO using anti-sense (AS) oligodeoxynucleotides (ODN) directed against iNOS mRNA. After culture of haemopoietic cells in the presence of AS-ODN, iNOS expression decreased and was no longer enhanced by Fas, This effect was associated with the prevention of Fas-mediated apoptosis, as determined by a DNA fragmentation and terminal deoxynucleotidyl transferase staining, In colony assays, specific AS-oligonucleotides prevented PAS-mediated inhibition of colony formation by total bone marrow and CD34(+) progenitor cells, Our data suggest that the inhibitory effects of Fas, including induction of apoptosis, are mediated by effector mechanisms that may be similar to those described for IFN-gamma and TNF-alpha. C1 UNIV NEVADA,DEPT INTERNAL MED,SCH MED,RENO,NV 89557. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. UNIV NAPLES FEDERICO II,SCH MED,DIV HAEMATOL,NAPLES,ITALY. NR 45 TC 36 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1997 VL 99 IS 3 BP 481 EP 489 DI 10.1046/j.1365-2141.1996.4323240.x PG 9 WC Hematology SC Hematology GA YK462 UT WOS:A1997YK46200002 PM 9401054 ER PT J AU Molldrem, JJ Caples, M Mavroudis, D Plante, M Young, NS Barrett, AJ AF Molldrem, JJ Caples, M Mavroudis, D Plante, M Young, NS Barrett, AJ TI Antithymocyte globulin for patients with myelodysplastic syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplastic syndrome; myeloid leukaemia; refractory anaemia; treatment; immunosuppression ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; APLASTIC-ANEMIA; PROGNOSTIC FACTORS; SCORING SYSTEM; BONE-MARROW; PHASE I/II; CLASSIFICATION; CHILDHOOD; INVITRO AB Twenty-five transfusion-dependent myelodysplastic syndrome (MDS) patients (with < 20% blasts) were treated in a phase II study with antithymocyte globulin (ATG) at 40 mg/kg/d for four doses and then followed with blood counts every 2 weeks and clinic visits every 3 months, for a median of 14 months (range 1-38 months), 11 (44%) patients responded and became transfusion-independent after ATG, including three complete responses, six partial responses, and two minimal responses. Responses were observed in 9/14 patients (64%) with refractory anaemia (RA) and 2/6 patients (33%) with refractory anaemia with excess blasts (RAEB). Median response duration was 10 months (range 3-38 months). The Kaplan-Meier estimate of overall survival was 84% at 38 months, with one early death due to pneumonia and two deaths from disease progression to leukaemia, Side-effects consisted mainly of mild serum sickness in all patients. A single course of ATG restored haemopoiesis in some patients with MDS and was well tolerated. C1 NHLBI,CLIN HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 35 TC 199 Z9 204 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1997 VL 99 IS 3 BP 699 EP 705 DI 10.1046/j.1365-2141.1997.4423249.x PG 7 WC Hematology SC Hematology GA YK462 UT WOS:A1997YK46200035 PM 9401087 ER PT J AU Knable, MB Egan, MF Heinz, A Gorey, J Lee, KS Coppola, R Weinberger, DR AF Knable, MB Egan, MF Heinz, A Gorey, J Lee, KS Coppola, R Weinberger, DR TI Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia - [I-123]-iodobenzamide SPECT study SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PARKINSONS-DISEASE; BASAL GANGLIA; TOMOGRAPHY; DEPRESSION; ALZHEIMERS; RECEPTORS; BINDING AB Background Previous in vivo studies of schizophrenia with dopamine D-2 receptor radioligands have yielded contradictory results. No prior study has used multiple scans to examine within-subject clinical change. Method Twenty-one patients were studied with [I-123]-iodobenzamide single photon emission computed tomography about two weeks after neuroleptic withdrawal. Thirteen of the 21 completed a second scan about four weeks after neuroleptic withdrawal. Sixteen controls were scanned for comparison. Results There was no significant difference between groups in [I-125]-iodobenzamide uptake at either scanning session. No significant correlations with demographic variables (age, illness duration, drug-free period), or clinical ratings (positive and negative symptoms, movement disorder) were observed at either scanning session. There was a significant correlation between change in [I-123]-iodobenzamide uptake and change in negative symptom ratings for the subjects who underwent two scans (r = 0.72, P < 0.05). Conclusions Worsening of negative symptoms may be associated with increased availability of striatal D-2 receptors, perhaps because of decreased concentrations of endogenous dopamine. C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH, Washington, DC 20032 USA. RP Knable, MB (reprint author), NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. NR 14 TC 42 Z9 42 U1 0 U2 0 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 DEC PY 1997 VL 171 BP 574 EP 577 DI 10.1192/bjp.171.6.574 PG 4 WC Psychiatry SC Psychiatry GA YL117 UT WOS:000070921600017 PM 9519100 ER PT J AU Bonkovsky, FO AF Bonkovsky, FO TI Minority minors and moral research medicine SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article RP Bonkovsky, FO (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 1997 VL 6 IS 1 BP 39 EP 47 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA WT922 UT WOS:A1997WT92200005 PM 9111960 ER PT J AU MacKay, C AF MacKay, C TI Planned parenthood SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Editorial Material RP MacKay, C (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 1997 VL 6 IS 1 BP 100 EP 100 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA WT922 UT WOS:A1997WT92200014 ER PT J AU Green, RM Fibison, WJ Hughes, MR AF Green, RM Fibison, WJ Hughes, MR TI Planned parenthood - Case commentary SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article ID PRENATAL-DIAGNOSIS C1 DARTMOUTH COLL,INST ETH,HANOVER,NH 03755. NATL INST NURSING RES,NIH,BETHESDA,MD. GEORGETOWN UNIV,MED CTR,INST MOL & HUMAN GENET,WASHINGTON,DC 20007. RP Green, RM (reprint author), NATL HUMAN GENOME RES INST,OFF GENOME ETH,NIH,BETHESDA,MD, USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 1997 VL 6 IS 1 BP 101 EP 105 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA WT922 UT WOS:A1997WT92200015 ER PT J AU Roth, MJ Liu, SF Dawsey, SM Zhou, B Copeland, C Wang, GQ Solomon, D Baker, SG Griffen, CA Taylor, PR AF Roth, MJ Liu, SF Dawsey, SM Zhou, B Copeland, C Wang, GQ Solomon, D Baker, SG Griffen, CA Taylor, PR TI Cytologic detection of esophageal squamous cell carcinoma and precursor lesions using balloon and sponge samplers in asymptomatic adults in Linxian, China SO CANCER LA English DT Article; Proceedings Paper CT 1996 Digestive Disease Week Meeting CY MAY 19-22, 1996 CL SAN FRANCISCO, CA SP Amer Gastroenterol Assoc DE cytology; esophageal neoplasms; precursor lesions; early detection; China ID CANCER; POPULATION; RISK AB BACKGROUND. The principal reason for the poor prognosis of esophageal carcinoma is that most tumors are asymptomatic and go undetected until they are unresectable. Previous studies have shown that cytologic screening of asymptomatic high risk individuals can detect curable esophageal carcinomas and precursor lesions, but the sensitivity of such screening is not well documented. The current study evaluated the sensitivity and specificity of currently available balloon and sponge cytologic samplers for detecting biopsy-proven squamous dysplasia and carcinoma in asymptomatic individuals from a high risk population in Linxian, China. METHODS. Asymptomatic adults were examined with both balloon and sponge samplers, in random order, followed by endoscopy with mucosal iodine staining and biopsy of all unstained lesions. The cytology slides were interpreted using the criteria of the Bethesda System. The balloon and sponge cytologic diagnoses (test) were compared with the biopsy diagnosis (truth) in each patient to estimate the sensitivity and specificity of each sampler. RESULTS. Of the 439 patients with adequate biopsies, 123 (28%) had histologic squamous dysplasia and 16 (4%) had an invasive squamous carcinoma. The sensitivities/specificities of the balloon and sponge were 44%/99% and 18%/100%, respectively, for detecting biopsy-proven squamous cell carcinoma, and 47%/81% and 24%/92%, respectively, for identifying squamous dysplasia or carcinoma. CONCLUSIONS. In this study, the balloon sampler was more sensitive than the sponge sampler for detecting esophageal squamous disease, but both techniques were less than optimal. Improved samplers and/or cytologic criteria should increase the sensitivities observed in this baseline study. (C) 1997 American Cancer Society. C1 CHINESE ACAD MED SCI,INST CANC,DEPT CYTOL,BEIJING 100021,PEOPLES R CHINA. NCI,CYTOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. CHINESE ACAD SCI,DEPT ENDOSCOPY,BEIJING,PEOPLES R CHINA. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Roth, MJ (reprint author), NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CN-45586] NR 41 TC 45 Z9 50 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1997 VL 80 IS 11 BP 2047 EP 2059 DI 10.1002/(SICI)1097-0142(19971201)80:11<2047::AID-CNCR3>3.0.CO;2-U PG 13 WC Oncology SC Oncology GA YG868 UT WOS:A1997YG86800003 PM 9392326 ER PT J AU Bartlett, DL Ma, G Alexander, HR Libutti, SK Fraker, DL AF Bartlett, DL Ma, G Alexander, HR Libutti, SK Fraker, DL TI Isolated limb reperfusion with tumor necrosis factor and melphalan in patients with extremity melanoma after failure of isolated limb perfusion with chemotherapeutics SO CANCER LA English DT Article; Proceedings Paper CT 49th Annual Society-of-Surgical-Oncology National Meeting CY MAR 21-24, 1996 CL ATLANTA, GA SP Soc Surg Oncol DE medical oncology; melanoma; in transit; metastases; limb perfusion; tumor necrosis factor; melphalan; hyperthermia ID MALIGNANT-MELANOMA; RECURRENT MELANOMA; INTERFERON-GAMMA; DOSE-ESCALATION; CISPLATIN; TOXICITY; PHARMACOKINETICS; ALPHA AB BACKGROUND, This retrospective study evaluated the benefit of using tumor necrosis factor (TNF) and melphalan administered via an isolated limb perfusion (ILP) in a series of patients with metastatic melanoma who failed initial ILP with chemotherapeutics. METHODS. Seventeen patients with extremity melanoma who underwent prior ILP with conventional chemotherapeutics (10 with melphalan; 4 with platinum; 2 with platinum, dacarbazine, thiotepa, actinomycin D, and nitrogen mustard; and 1 with thiotepa, actinomycin D, and nitrogen mustard) and had local recurrences were treated with a 90-minute isolated hyperthermic limb reperfusion with melphalan (10 mg/L limb volume) plus TNF (2-6 mg). Five prior ILPs were adjuvant and 12 were therapeutic. RESULTS. Reperfusion was associated with an overall 94% response rate and a 65% complete response (CR) rate. Of the patients who failed an initial ILP with melphalan alone the overall response rate was 90% after the reperfusion with TNF and melphalan. In patients who failed an initial ILP with agents other than melphalan the CR rate was 100% after ILP with TNF and melphalan. TNF/melphalan isolated limb reperfusion was found to be more effective in terms of CR after initial ILP regimens that did not utilize melphalan (100% CR after nonmelphalan ILP vs. 50% CR after melphalan ILP [P = 0.04]). Regional toxicity was comprised of mild skin blistering and peeling in 47% of patients. One patient developed Grade 3 (based on National Cancer Institute Common Toxicity Criteria) skin necrosis, and one developed Grade 5 muscle and nerve toxicity, requiring an amputation. CONCLUSIONS. Isolated limb reperfusion with TNF and melphalan can be performed safely with response rates similar to those of other trials of single perfusions. Repeat ILP using TNF and melphalan in patients with melanoma who have failed prior ILP with chemotherapeutics is justified. The utility of TNF (vs. melphalan alone) will be defined in ongoing Phase III trials. (C) 1997 American Cancer Society. C1 HOSP UNIV PENN,DEPT SURG,PHILADELPHIA,PA 19104. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 27 TC 52 Z9 52 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1997 VL 80 IS 11 BP 2084 EP 2090 DI 10.1002/(SICI)1097-0142(19971201)80:11<2084::AID-CNCR7>3.0.CO;2-X PG 7 WC Oncology SC Oncology GA YG868 UT WOS:A1997YG86800007 PM 9392330 ER PT J AU Woo, ES Monks, A Watkins, SC Wang, AS Lazo, JS AF Woo, ES Monks, A Watkins, SC Wang, AS Lazo, JS TI Diversity of metallothionein content and subcellular localization in the National Cancer Institute tumor panel SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE tumor cells; immunofluorescence; chemotherapy; metals ID ANTICANCER DRUG SCREEN; CELL-LINES; IMMUNOHISTOCHEMICAL LOCALIZATION; TRANSGENIC MICE; RAT-LIVER; RESISTANCE; EXPRESSION; PROTECTS; CADMIUM; DNA AB Metallothioneins (MTs) are major thiol-containing intracellular proteins that bind metals, are induced by stress, and have been implicated in resistance to drugs and heavy metals. Pur pose: To examine the hypothesis that the protective functionality of MT may be dictated by its subcellular localization. Methods: We analyzed the basal MT content in 53 adherent cell lines of the National Cancer Institute (NCI) tumor panel and quantified the nuclear/cytoplasmic distribution of MT using confocal laser scanning microscopy and a recently described immunofluorescence-based algorithm. Results: Among these cell types we found a 400-fold range in the basal MT levels and a tenfold range in the ratio of the nuclear to cytoplasmic MT immunostaining that was independent of basal MT content. Total MT levels and nuclear/cytoplasmic distribution were independent of total glutathione content, suggesting autonomous regulation of these protective protein and nonprotein thiol pools. Approximately 50% (29/53) of the cell lines had a greater nuclear than cytoplasmic MT density and were defined as having a karyophilic phenotype. Tissue specificity of MT localization was seen with breast cancer cell lines, which were cytoplasmophilic, whereas prostate-derived cells were karyophilic. Among the 25000 unrestricted compounds in the NCI database, we detected a correlation between total basal MT levels and resistance to CdCl2, four Pt- and two Cu-containing compounds. High nuclear/cytoplasmic MT values correlated with resistance to six Cu-, six Pb-, and one Zn-containing compounds. Conclusions: These results demonstrated significant diversity in MT content and subcellular localization in human tumor cells. Moreover, both basal MT levels and subcellular distribution appeared to be determinants of cellular responsiveness to metal-containing compounds. C1 UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,DEPT CELL BIOL & PHYSIOL,PITTSBURGH,PA 15261. UNIV PITTSBURGH,INST CANC,EXPT THERAPEUT PROGRAM,PITTSBURGH,PA 15261. NCI,FREDERICK CANC RES FACIL,SAIC FREDERICK,FREDERICK,MD 21701. FU NCI NIH HHS [CA62781, CA61299] NR 34 TC 36 Z9 36 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 1997 VL 41 IS 1 BP 61 EP 68 DI 10.1007/s002800050708 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA YK938 UT WOS:A1997YK93800009 PM 9443615 ER PT J AU Amar, S Glozman, A Chung, D Adler, V Ronai, Z Friedman, FK Robinson, R BrandtRauf, P Yamaizumi, Z Pincus, MR AF Amar, S Glozman, A Chung, D Adler, V Ronai, Z Friedman, FK Robinson, R BrandtRauf, P Yamaizumi, Z Pincus, MR TI Selective inhibition of oncogenic ras-p21 in vivo by agents that block its interaction with jun-N-kinase (JNK) and jun proteins. Implications for the design of selective chemotherapeutic agents SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE selective inhibition; oncogenic ras-p21; jun-N-kinase; jun proteins ID ENCODED P21 PROTEIN; OOCYTE MATURATION; XENOPUS OOCYTES; BINDING DOMAIN; GROWTH-FACTOR; RAS PROTEINS; WILD-TYPE; ACTIVATION; TRANSFORMATION; P21(RAS) AB We have obtained evidence that oncogenic and activated normal ras-p21 proteins utilize overlapping but distinct signal transduction pathways. Recently, we found that ras-p21 binds to both jun and its kinase, jun kinase (JNK). We now present evidence that suggests that oncogenic but not normal activated p21 depends strongly on early activation of JNK/jun. This early activation most likely involves direct interaction between oncogenic p21 and JNK/jun because p21 peptides that blocked the binding of p21 to JNK and jun strongly inhibited oncogenic p21-induced oocyte maturation while they did not inhibit insulin-activated normal cellular p21-induced maturation. Very similar results were also obtained for a newly characterized specific inhibitor of JNK which blocked oncogenic but not normal activated p21-induced oocyte maturation. We also found that both jun and JNK strongly enhanced oncogenic p21-induced oocyte maturation while they inhibited insulin-activated normal p21-induced oocyte maturation. These results suggest that the peptides and JNK inhibitor may be useful agents in selectively blocking the effects of oncogenic but not normal p21 in cells. C1 VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY 11203. LONG ISL UNIV,DEPT CHEM,BROOKLYN,NY. LONG ISL UNIV,DEPT BIOL,BROOKLYN,NY. AMER HLTH FDN,MOL CARCINOGENESIS DIV,VALHALLA,NY 10595. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10032. NATL CANC CTR,RES INST,TOKYO 104,JAPAN. RI Friedman, Fred/D-4208-2016; OI RONAI, ZEEV/0000-0002-3859-0400 FU NCI NIH HHS [CA 42500] NR 33 TC 26 Z9 26 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 1997 VL 41 IS 1 BP 79 EP 85 DI 10.1007/s002800050711 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA YK938 UT WOS:A1997YK93800012 PM 9443618 ER PT J AU Rothman, N Talaska, G Hayes, RB Bhatnagar, VK Bell, DA Lakshmi, VM Kashyap, SK Dosemeci, M Kashyap, R Hsu, FF Jaeger, M Hirvonen, A Parikh, DJ Davis, BB Zenser, TV AF Rothman, N Talaska, G Hayes, RB Bhatnagar, VK Bell, DA Lakshmi, VM Kashyap, SK Dosemeci, M Kashyap, R Hsu, FF Jaeger, M Hirvonen, A Parikh, DJ Davis, BB Zenser, TV TI Acidic urine pH is associated with elevated levels of free urinary benzidine and N-acetylbenzidine and urothelial cell DNA adducts in exposed workers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BLADDER-CANCER; HYDROXY METABOLITES; GLUCURONIDATION; LIVER; DOG; 4-AMINOBIPHENYL; CARCINOGEN; RAT; MUTAGENICITY; ARYLAMINES AB We evaluated the influence of urine pH on the proportion of urinary benzidine (BZ) and N-acetylbenzidine present in the free, unconjugated state and on exfoliated urothelial cell DNA adduct levels in 32 workers exposed to BZ in India, Postworkshift urine pH was inversely correlated with the proportions of BZ (r = -0.78; P < 0.0001) and N-acetylbenzidine (r = -0.67; P < 0.0001) present as free compounds, Furthermore, the average of each subject's pre-and postworkshift urine pH was negatively associated with the predominant urothelial DNA adduct (P = 0.0037, adjusted for urinary BZ and metabolites), which has been shown to cochromatograph with a N-(3'-phosphodeoxyguanosin-8-yl)-N'acetylbenzidine adduct standard, Controlling for internal dose, individuals,vith urine pH <6 had 10-fold higher DNA adduct levels compared to subjects with urine pH greater than or equal to 7. As reported previously, polymorphisms in NAT1, NAT2, and GSTM1 had no impact on DNA adduct levels, This is the first study to demonstrate that urine pH has a strong influence on the presence of free urinary aromatic amine compounds and on urothelial cell DNA adduct levels in exposed humans, Because there is evidence that acidic urine has a similar influence on aromatic amines derived from cigarette smoke, urine pH, which is influenced by diet, may be an important susceptibility factor for bladder cancer caused by tobacco in the general population. C1 Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Inst Occupat Hlth, Ahmedabad 380016, Gujarat, India. St Louis Univ, Sch Med, St Louis, MO 63125 USA. Vet Affairs Med Ctr, St Louis, MO 63125 USA. RP Rothman, N (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, EPN 418, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR-00954]; NIADDK NIH HHS [AM-20579]; NIEHS NIH HHS [1-P30-ES06096-01] NR 22 TC 43 Z9 43 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1997 VL 6 IS 12 BP 1039 EP 1042 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YP217 UT WOS:000071254300010 PM 9419400 ER PT J AU Palli, D Caporaso, NE Shiao, YH Saieva, C Amorosi, A Masala, G Rice, JM Fraumeni, JF AF Palli, D Caporaso, NE Shiao, YH Saieva, C Amorosi, A Masala, G Rice, JM Fraumeni, JF TI Diet, Helicobacter pylori, and p53 mutations in gastric cancer: A molecular epidemiology study in Italy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TUMOR-SUPPRESSOR GENE; STOMACH-CANCER; FREQUENT LOSS; REDUCED RISK; CELL-LINES; HETEROZYGOSITY; CARCINOMA; NUTRIENTS; HISTORY; AREAS AB A series of 105 gastric cancer (GC) cases with paraffin-embedded specimens interviewed in a previous population-based case-control study conducted in a highrisk area around Florence, Italy, was examined for the presence of p53 mutations, Overall, 33 of 105 cases had a mutation (p53(+)) identified by single-strand conformational polymorphism and confirmed by sequencing (Y-H, Shiao ed at, submitted for publication), p53(+) cases had a more traditional dietary pattern (i.e., corn meal mush, meat soup, and other homemade dishes) and reported less frequent consumption of raw vegetables (particularly lettuce and raw carrots), A positive association with a high nitrite intake and a negative association with raw vegetables and diffuse type histology persisted in a multivariate analysis, In addition, p53(+) cases tended to be located in the upper portion of the stomach and to be associated with advanced age and blood group A, No relation was found between the presence of p53 mutations and histologically defined Helicobacter pylori infection, smoking history, family history of gastric cancer, education, and social class. Of the 33 p53(+) cases, 19 had G:C-->A:T transitions at CpG sites, These tumors tended to occur in females and in association with H. pylori infection but not other risk factors, The remaining 14 cases with a p53 mutation had mainly transversions but also two deletions and two transitions at non-CpG sites, These tumors showed a strong positive association with a traditional dietary pattern and with the estimated intake of selected nutrients (nitrite, protein, and fat, particularly from animal sources), The findings of this ease-case analysis suggest that p53 mutations at non-CpG sites are related to exposure to alkylating compounds from diet, whereas p53 mutations at CpG sites might be related to H. pylori infection. C1 Ctr Studio & Prevenz Oncol, Epidemiol Unit, Analyt Epidemiol Unit, AO Careggi, I-50131 Florence, Italy. NCI, Comparat Carcinogenesis Lab, Bethesda, MD 20892 USA. CSPO, IST Genoa, Satellite Epidemiol Unit, Florence, Italy. Univ Florence, Dept Pathol, I-50121 Florence, Italy. RP Palli, D (reprint author), Ctr Studio & Prevenz Oncol, Epidemiol Unit, Analyt Epidemiol Unit, AO Careggi, Viale A Volta 171, I-50131 Florence, Italy. OI saieva, calogero/0000-0002-0117-1608; PALLI, Domenico/0000-0002-5558-2437; Masala, Giovanna/0000-0002-5758-9069 NR 31 TC 36 Z9 37 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1997 VL 6 IS 12 BP 1065 EP 1069 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YP217 UT WOS:000071254300014 PM 9419404 ER PT J AU Chen, VW Fenoglio-Preiser, CM Wu, XC Coates, RJ Reynolds, P Wickerham, DL Andrews, P Hunter, C Stemmermann, G Jackson, JS Edwards, BK AF Chen, VW Fenoglio-Preiser, CM Wu, XC Coates, RJ Reynolds, P Wickerham, DL Andrews, P Hunter, C Stemmermann, G Jackson, JS Edwards, BK CA Natl Canc Inst Black White Canc Surv TI Aggressiveness of colon carcinoma in blacks and whites SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; RACIAL-DIFFERENCES; SURVIVAL; INSTABILITY; RACE AB Black patients with colon cancer in the Black/White Cancer Survival Study were found to have a poorer survival than white patients. More advanced-stage disease at diagnosis was the primary determinant, accounting for 60% of the excess mortality. After adjusting for stage, factors such as poverty, other socioeconomic conditions, and treatment did not further explain the remaining survival deficit. This study examined the aggressiveness of colon tumors in blacks and whites to explore its role in the racial survival differences. Tumor characteristics of 703 cases of newly diagnosed invasive colon adenocarcinoma were centrally evaluated by a gastrointestinal pathologist, blinded in regard to the age, race, and sex of the patients. Blacks were less likely to have poorly differentiated (grade 3) tumors [odds ratio (OR), 0.44; 95% confidence interval, 0.22-0.88] and lymphoid reaction (OR, 0.49; 95% confidence interval, 0.26-0.90) when compared with whites. These black/white (B/W) differences remained statistically significant after adjusting for age, sex, metropolitan area, summary stage, socioeconomic status, body mass index, and health care access and utilization. Tn addition, blacks were less likely to have high-grade (grade 3) nuclear atypia, mitotic activity, and tubule formation, although these ORs did not reach a statistical significance level of 0.05. Similar B/W differences were observed for patients with advanced disease but not with early stage. Comparison by anatomical subsite showed that blacks had statistically significantly better differentiated tumors for cancers of the proximal and transverse colon but not for the distal. No racial differences were found for blood vessel and lymphatic invasion, necrosis, fibrosis, and mucinous type of histology. The findings, therefore, are the opposite of those hypothesized. After adjusting for stage, more aggressive tumor characteristics do not explain the adverse survival differential in blacks. This suggests that there may be racial differences in environmental exposure, and that the intensity and mode of delivery of carcinogen insult as web as host susceptibility may differ by race and anatomical subsite. Future studies should explore the B/W differences in tumor biology using molecular markers that precede the conventional histological parameters evaluated here. C1 Louisiana State Univ, Med Ctr, Dept Pathol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Univ Cincinnati, Med Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Calif State Dept Hlth Serv, Emeryville, CA 94608 USA. Allegheny Univ, Pittsburgh, PA USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Chen, VW (reprint author), Louisiana State Univ, Med Ctr, Dept Pathol, Box P5-1,1901 Periddo St, New Orleans, LA 70112 USA. FU NCI NIH HHS [N01-CN-45176, N01-CN-45174, N01-CN-45175] NR 27 TC 82 Z9 83 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1997 VL 6 IS 12 BP 1087 EP 1093 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YP217 UT WOS:000071254300018 PM 9419408 ER PT J AU Fisher, RI Rosenberg, SA Sznol, M Parkinson, DR Fyfe, G AF Fisher, RI Rosenberg, SA Sznol, M Parkinson, DR Fyfe, G TI High dose aldesleukin in renal cell carcinoma: Long term survival update SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT Conference on Interleukin-2 in Metastatic Melanoma - Establishing a Role CY JUL 10-13, 1997 CL SAN FRANCISCO, CALIFORNIA DE immunotherapy; interleukin-2; renal cell carcinoma ID ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2 THERAPY; CONTINUOUS INFUSION INTERLEUKIN-2; PHASE-II TRIAL; CANCER; BOLUS AB PURPOSE This article updates response duration and survival data for patients with metastatic renal cell carcinoma receiving high-dose recombinant interleukin-2 (rIL-2). PATIENTS AND METHODS Two hundred fifty-five assessable renal cell carcinoma patients were entered into seven phase II clinical trials, They were administered 600,000 or 720,000 IU/kg rIL-2 by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximal support, A second identical cycle of treatment a as scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients, All data have been updated as of June 1996 with report forms completed by the clinical investigators. RESULTS Objective overall responses have now been achieved in 37 of 255 patients (15%) with 17 complete (7%) and 20 (8%) responses, Median response duration for all objective responders is 54 months with a range of 3 to 107+ months, Median response duration for all complete responses has nor been reached, with a range of 7 to 107+ months, Median response duration for all partial responses is 20 months, with a range of 3 to 97+ months, Median survival for all 255 patients was 16.3 months, and 10% to 20% of patients were estimated to be alive 5 to 10 years following treatment, CONCLUSION Treatment with high-dose rIL-2 is extremely effective for a subset of patients with metastatic renal cell carcinoma. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. NCI, Bethesda, MD 20892 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Fisher, RI (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, 2160 S 1St Ave,Room 255, Maywood, IL 60153 USA. NR 10 TC 58 Z9 58 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD DEC PY 1997 VL 3 SU 1 BP S70 EP S72 PG 3 WC Oncology SC Oncology GA YV783 UT WOS:000071862900014 PM 9457398 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Keynote address: Perspectives on the use of interleukin-2 in cancer treatment SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT Conference on Interleukin-2 in Metastatic Melanoma - Establishing a Role CY JUL 10-13, 1997 CL SAN FRANCISCO, CALIFORNIA ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; AUTOLOGOUS TUMOR; IMMUNOTHERAPY; IDENTIFICATION; PEPTIDES; CLONING C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Div Clin Sci, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD DEC PY 1997 VL 3 SU 1 BP S2 EP S6 PG 5 WC Oncology SC Oncology GA YV783 UT WOS:000071862900001 PM 9457385 ER PT J AU Yang, JC Rosenberg, SA AF Yang, JC Rosenberg, SA TI An ongoing prospective randomized comparison of interleukin-2 regimens for the treatment of metastatic renal cell cancer SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT Conference on Interleukin-2 in Metastatic Melanoma - Establishing a Role CY JUL 10-13, 1997 CL SAN FRANCISCO, CALIFORNIA DE cytokine; immunotherapy; interleukin-2; randomized clinical trial; renal cell carcinoma ID DOSE RECOMBINANT INTERLEUKIN-2; PHASE-II; CARCINOMA; INVIVO; TRIAL AB PURPOSE This article compares the pharmarokinetics, toxicity, and clinical efficacy of high-dose intravenous, low-dose intravenous, and intermediate-dose subcutaneous recombinant interleukin-2 (rIL-2) regimens in patients with measurable metastatic renal cell carcinoma. PATIENTS AND METHODS This trial began as a mio-arm randomized study comparing two bolus intravenous rIL-2 regimens. High-dose (720,000 IU/kg) and low-dose (72,000 IU/kg) rIL-2 were administered every 8 hours for up to 15 consecutive doses. Later, a third arm of outpatient subcutaneous rIL-2 (week 1: 250,000 IU/kg/day for 5 of 7 days; weeks 2-6: 125,000 IU/kg/day for 5 of 7 da;ra) was added, and only concurrently randomized patients were compared. A sample of patients underwent pharmacokinetic studies of serum IL-2 levels following their first dose. Accrual to this study is ongoing and results are preliminary. RESULTS In the two-arm comparison of high-dose versus low-dose intravenous rIL-2, 116 and 112 patients have been randomized, respectively, and the median follow-up is 52 months. Low-dose rIL-2 induced significantly less hypotension, thrombocytopenia, malaise, pulmonary toxicity, and neurotoxicity than high-dose rIL-2. The initial overall response rate (partial plus complete responses) was 19% with high-dose rIL-2 and 10% with low-dose rIL-2. Responses to high-dose rIL-2 tended to be more durable. With 54 to 56 patients randomized per arm in the three-arm comparison, the high-dose intravenous, low-close intravenous, and subcutaneous outpatient rIL-2 regimens have produced response rates of 16%, 4%, and 11%, respectively. Subcutaneous rIL-2 therapy was frequently associated with grade 3 or 4 toxicity (similar to low-dose intravenous rIL-2 therapy). Survival data remain incomplete with median follow-up in the three-arm trial at 27 months. DISCUSSION The optimal IL-2 regimen for treating metastatic renal cell carcinoma is not known. Alternative regimens with much less acute toxicity than high-dose IL-2 can cause regression of renal cell carcinoma, but duration of therapy, chronicity of symptoms, and quality-of-life issues may be important in properly evaluating the tolerability of different regimens. Because the main benefit of IL-2 therapy is not its initial response rate but its induction of durable, complete responses, further accrual and follow-up will be necessary to compare properly the impact of these regimens on patient survival. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), Room 2B-37,Bldg 10,9000 Rockville Piki, Bethesda, MD 20892 USA. NR 11 TC 62 Z9 61 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD DEC PY 1997 VL 3 SU 1 BP S79 EP S84 PG 6 WC Oncology SC Oncology GA YV783 UT WOS:000071862900016 PM 9457400 ER PT J AU Cole, DJ Wilson, MC Rivoltini, L Custer, M Nishimura, MI AF Cole, DJ Wilson, MC Rivoltini, L Custer, M Nishimura, MI TI T-cell receptor repertoire in matched MART-1 peptide-stimulated peripheral blood lymphocytes and tumor-infiltrating lymphocytes SO CANCER RESEARCH LA English DT Article ID HUMAN-MELANOMA; GENE SEGMENT; IN-VIVO; ANTIGEN; IMMUNOTHERAPY; RECOGNITION; CLONES; IDENTIFICATION; USAGE; CTL AB Characterization of tumor-associated antigens (TAAs) recognized by CTLs makes the consideration of therapeutic strategies based on peptide stimulation of peripheral blood lymphocytes (PBLs) feasible, Several such approaches are adoptive transfer of peptide-stimulated PBLs, ex vivo peptide stimulation of dendritic cells, and direct vaccination with TAA-derived peptides, A critical component of any of these peptide-based strategies is the requirement that the patient's PBLs are able to react productively against the presented TAA. The purpose of this study, through the study of T-cell receptor (TCR) usage, was to evaluate the T-cell response in matched MART-1((27-35)) peptide-stimulated PBLs and tumor-infiltrating lymphocytes (TTLs), MART-1((27-35)) reactive PBL and TIL cultures were generated from three patients by in vitro stimulation with an immunodominant peptide of MART-1 MART-1((27-35))). All cultures had a human leukocyte antigen A2-restricted, MART-1((27-35))-specific CTL response, The TCR usage of each was assessed by the DNA sequence analysis of 50 TCR beta clones obtained by rapid amplification of cDNA ends per culture, TCR analysis suggests a TCR repertoire that differed from patient to patient (8-16 sulbfamilies were used) and a predominant usage of a different variable beta chain (BV) by each of these MART-reactive T cells, These predominant BV rearrangements were derived from multiple clonotypes because different variable, diversity, and junctional regions were observed. However, a similar pattern of expansion was present for both PBLs and TILs; the relative usage of each prevailing BV was more marked in TILs (36, 50, and 75% of TILs versus 26, 20, and 24% of PBLs, respectively), a broader TCR repertoire was used by PBLs (P > 0.05), and similar TCR subfamily usage was noted when TIL and PDL cultures from the same patient were compared (8 of 11, 7 of 9, and 7 of 8 for patients 1, 2, and 3, respectively). Furthermore, the exact same clonotypes derived from predominant TCR subfamilies in the PBLs and TILs were present in each patient, suggesting peptide-stimulated expansion in both biological compartments, These studies suggest that there will not be a limited and predictable TCR subfamily response to a specific TAA, although reproducible patterns of PBL and TIL expansion are present from patient to patient, Additionally, identical T-cell clonotypes having the same potential fur antigen-driven expansion were present in a patient's PBLs and TILs, As such, our data support the conceptualization of approaches using adoptive transfer or vaccination based on TAA-derived peptide stimulation of PBLs. C1 MED UNIV S CAROLINA,HOLLINGS CANC CTR,CHARLESTON,SC 29425. NATL TUMOR INST MILAN,I-20133 MILAN,ITALY. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. RP Cole, DJ (reprint author), MED UNIV S CAROLINA,DEPT SURG,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. OI Rivoltini, Licia/0000-0002-2409-6225 NR 46 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1997 VL 57 IS 23 BP 5320 EP 5327 PG 8 WC Oncology SC Oncology GA YH980 UT WOS:A1997YH98000023 PM 9393756 ER PT J AU Jiang, BH Agani, F Passaniti, A Semenza, GL AF Jiang, BH Agani, F Passaniti, A Semenza, GL TI V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: Involvement of HIF-1 in tumor progression SO CANCER RESEARCH LA English DT Article ID LACTATE-DEHYDROGENASE-A; FACTOR MESSENGER-RNA; ROUS-SARCOMA VIRUS; C6 GLIOMA-CELLS; POSTTRANSCRIPTIONAL REGULATION; PHOSPHOGLYCERATE KINASE-1; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; IN-VIVO; ANGIOGENESIS AB Adaptation to hypoxia represents an important aspect of tumor progression, Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates essential homeostatic responses to cellular and systemic hypoxia by activating transcription of multiple genes including those encoding glycolytic enzymes and vascular endothelial growth factor (VFGF). In this report, we demonstrate that whereas C-SXC expression is not required for expression of KIF-I or transcriptional activation of genes encoding VEGF and enolase 1 (ENO1). cells expressing the v-Src oncogene have increased expression of HiF-1, VEGF, and ENO1 under both hypoxic and nonhypoxic conditions, Expression of V-SRC was associated with increased transcription of reporter genes containing cis-acting hypoxia-response elements from the VEGF and ENO1 genes, and this transcriptional activation required an intact RIF-I binding site. When three rat hepatoma subclones that differed with respect to the level of NIF-I expression were injected into nude mice, tumor growth correlated with HIF-1 expression, suggesting that HIF-1 mag be generally involved in tumor progression, These studies link an oncogene to the induction of HIF-1 expression, thus providing a mechanism for hypoxic adaptation by tumor cells. C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,DEPT MED,BALTIMORE,MD 21205. NIA,NIH,BALTIMORE,MD 21224. FU NHLBI NIH HHS [R01-HL55338]; NIDDK NIH HHS [R01-DK39869] NR 71 TC 418 Z9 431 U1 1 U2 13 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 DEC 1 PY 1997 VL 57 IS 23 BP 5328 EP 5335 PG 8 WC Oncology SC Oncology GA YH980 UT WOS:A1997YH98000024 PM 9393757 ER PT J AU Koochekpour, S Jeffers, M Rulong, S Taylor, G Klineberg, E Hudson, EA Resau, JH Woude, GFV AF Koochekpour, S Jeffers, M Rulong, S Taylor, G Klineberg, E Hudson, EA Resau, JH Woude, GFV TI Met and hepatocyte growth factor scatter factor expression in human gliomas SO CANCER RESEARCH LA English DT Article ID C-MET; CELLS; RECEPTOR; TUMORIGENICITY; MORPHOGENESIS; PROLIFERATION; CONCOMITANT; METASTASIS; INDUCTION; MOTILITY AB Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas, HGF/SF and Met also are expressed in vitro in glioblastoma multiforme cell lines as well as in normal human astrocyte (NHA) cells, Moreover, HGF/SF stimulates tyrosine phosphorylation of Met in both glioma cell lines and NHA cells, but only the glioma cell lines proliferate and become motile and invasive in response to HGF/SF, whereas the NHA cells are nonresponsive, These results implicate autocrine/paracrine Met-HGF/SF signaling in glioma tumorigenesis and suggest that HGF/SF signaling through Met is negatively regulated in NHA cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 30 TC 235 Z9 239 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 DEC 1 PY 1997 VL 57 IS 23 BP 5391 EP 5398 PG 8 WC Oncology SC Oncology GA YH980 UT WOS:A1997YH98000032 PM 9393765 ER PT J AU Smith, ML Fornace, AJ AF Smith, ML Fornace, AJ TI p53-null cells are more sensitive to ultraviolet light only in the presence of caffeine. SO CANCER RESEARCH LA English DT Letter ID LI-FRAUMENI SYNDROME; DNA-REPAIR; EXCISION-REPAIR; P53; MUTAGENESIS; MUTATIONS; RADIATION; APOPTOSIS; AGENTS; GENE RP Smith, ML (reprint author), NCI,DIV BASIC SCI,NIH,BLDG 37,ROOM 5D02,BETHESDA,MD 20892, USA. NR 19 TC 3 Z9 3 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 DEC 1 PY 1997 VL 57 IS 23 BP 5434 EP 5435 PG 2 WC Oncology SC Oncology GA YH980 UT WOS:A1997YH98000039 PM 9393772 ER PT J AU Batta, G Liptak, A Schneerson, R Pozsgay, V AF Batta, G Liptak, A Schneerson, R Pozsgay, V TI Conformational stabilization of the altruronic acid residue in the O-specific polysaccharide of Shigella sonnei Plesiomonas shigelloides SO CARBOHYDRATE RESEARCH LA English DT Article DE altruronic acid; NMR spectroscopy; Plesiomonas shigelloides; Polysaccharide conformation; Shigella sonnei; O-specific polysaccharide ID MULTIPLE-QUANTUM COHERENCE; HIGH-RESOLUTION; SPECTROSCOPY; NMR; LIPOPOLYSACCHARIDE; INFECTIONS; TYPE-1 AB Complete assignments for the H-1- and the C-13-NMR spectra of the O-specific polysaccharide of S. sonnei/Plesiomonas shigelloides are reported. Evidence is presented that in this polysaccharide both pyranose residues exist preferentially in the C-4(1) chair conformation and that the polysaccharide exists in the zwitterion form. (C) 1998 Elsevier Science Ltd. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Antibiot Res Grp, H-4010 Debrecen, Hungary. Hungarian Acad Sci, Res Grp Carbohydrates, H-4010 Debrecen, Hungary. Lajos Kossuth Univ, Inst Biochem, H-4010 Debrecen, Hungary. RP Pozsgay, V (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RI Batta, Gyula/H-4567-2011 OI Batta, Gyula/0000-0002-0442-1828 NR 25 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC PY 1997 VL 305 IS 1 BP 93 EP 99 DI 10.1016/S0008-6215(97)00197-3 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA ZA091 UT WOS:000072328000009 PM 9534229 ER PT J AU Newbold, RR Jefferson, WN Padilla-Burgos, E Bullock, BC AF Newbold, RR Jefferson, WN Padilla-Burgos, E Bullock, BC TI Uterine carcinoma in mice treated neonatally with Tamoxifen SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER; GENITAL-TRACT; ESTROGEN-RECEPTOR; GUINEA-PIG; DIETHYLSTILBESTROL; ANTIESTROGENS; PREVENTION; EXPOSURE; UTERUS; ADENOCARCINOMA AB The induction of preneoplastic and neoplastic lesions by the widely used antiestrogen Tamoxifen was studied in female mice, Outbred CD-1 mice were treated with Tamoxifen (1, 2, 5, 10, 25 or 50 mu g/pup/day) for the first 5 days after birth, At 14-17 months, reproductive tract tissues were examined for pathological changes, In the ovary, corpora lutea were lacking while cysts were quite common in Tamoxifen-exposed mice at all doses; cystadenomas mere seen in two mice, Structural malformations and epithelial hyperplasia of the oviduct were seen in 100% of the treated mice, Malformations of the uterus, cervix, and vagina were also seen, Excessive vaginal keratinization was not a common feature although vaginal adenosis was observed more often after Tamoxifen treatment than previously reported after similar treatment with diethylstilbestrol (DES), The most striking histological features, however were seen in the uterus, One hundred percent of the Tamoxifen-treated mice at all doses exhibited uterine hypoplasia with focal areas of basal cell hyperplasia in the lining endometrium. Progressive cellular atypias were seen in the lining endometrium ranging from atypical hyperplasia to uterine adenocarcinoma; the highest incidence of uterine adenocarcinoma was 7/14 (50%) observed in the Tamoxifen 10 mu g/pup/day dose group, No similar tumors were observed in corresponding control mice, The induction of atypical uterine hyperplasia and adenocarcinoma combined with other abnormalities observed in genital tract structure following neonatal treatment with Tamoxifen suggests the developing reproductive tract is exquisitely sensitive to perturbation by compounds with hormonal activity, These studies provide the basis for future investigation into the mechanisms of Tamoxifen's carcinogenic effects in experimental animals, and to the risk benefit analysis for the prophylactic use of Tamoxifen in healthy women who are at risk of developing breast cancer. C1 NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Comparat Med, Winston Salem, NC 27103 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 41 TC 66 Z9 67 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1997 VL 18 IS 12 BP 2293 EP 2298 DI 10.1093/carcin/18.12.2293 PG 6 WC Oncology SC Oncology GA YQ808 UT WOS:000071425200001 PM 9450472 ER PT J AU Khan, QA Vousden, KH Dipple, A AF Khan, QA Vousden, KH Dipple, A TI Cellular response to DNA damage from a potent carcinogen involves stabilization of p53 without induction of p21(waf1/cip1) SO CARCINOGENESIS LA English DT Article ID BENZOPYRENE DIOL EPOXIDE; FEMALE CD RATS; FJORD REGION; MAMMARY CARCINOGENICITY; ADDUCTS; PROTEIN; CELLS; BENZOPHENANTHRENE; DIBENZOPYRENE; BENZOCHRYSENE AB The effect of a potent mammary carcinogen, anti benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide, on the progress of human mammary carcinoma MCF-7 cells through the cell cycle was investigated, While these cells, which express wild-type p53, were arrested in G1 after treatment with actinomycin D (a positive control), treatment with the mammary carcinogen did not cause G1 arrest but instead delayed the cells in the DNA synthesis phase, In concert with the absence of a GI arrest, it was found that though both chemical treatments led to increased levels of p53, only the p53 induced by actinomycin D was transcriptionally active and increased the levels of the cyclin dependent kinase inhibitor, p21(waf1/cip1). Since treatment of the cells with the mammary carcinogen did not abrogate the G1 arrest induced by actinomycin D, the lack of p21(waf1/cip1) and of G1 arrest, resulting from treatment with the mammary carcinogen alone, was not due to some general inhibition of transcription or translation, An analogous difference between these two chemicals was demonstrated also in other human cell systems, The stealth-like property of the mammary carcinogen that allows it to damage DNA without turning on the cells' 'guardian of the genome' defense mechanism presumably increases the likelihood of malignant change because DNA replication continues on a damaged template, It is suggested that this stealth characteristic may be a major contributor to the high carcinogenic potency of this mammary carcinogen and possibly to that of other highly potent carcinogens. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Virol & Carcinogenesis Lab, Frederick, MD 21702 USA. RP Dipple, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 44 TC 45 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1997 VL 18 IS 12 BP 2313 EP 2318 DI 10.1093/carcin/18.12.2313 PG 6 WC Oncology SC Oncology GA YQ808 UT WOS:000071425200004 PM 9450475 ER PT J AU Sung, V Venkateshan, CN Williamson, L Ward, R Espey, MG Gibbs, CJ Moffett, JR Namboodiri, MAA AF Sung, V Venkateshan, CN Williamson, L Ward, R Espey, MG Gibbs, CJ Moffett, JR Namboodiri, MAA TI Immuno-electron microscopy reveals that the excitotoxin quinolinate is associated with the plasma membrane in human peripheral blood monocytes/macrophages SO CELL AND TISSUE RESEARCH LA English DT Article DE quinolinic acid; interferon-gamma; kynurenine; electron microscopy; immunocytochemistry; excitotoxicity; human ID ACID; RAT; CAVEOLAE; CELLS; LOCALIZATION; DISPOSITION; MACROPHAGES; ANTIBODIES; SYSTEM AB Quinolinate (QUIN), a tryptophan-derived excitotoxin, was localized ultrastructurally in human peripheral blood monocytes/macrophages (M empty set) by immune-electron microscopy. A combined carbodiimide/glutaraldehyde/paraformaldehyde-based fixation procedure was developed for optimal retention of QUIN in the cell as well as minimal loss of ultrastructure; a silver-enhanced colloidal gold detection system was used for electron-microscopic analysis. Gold particles representing QUIN immunoreactivity were associated with the inner side of the plasma membrane in normal M empty set. The number of gold particles increased significantly when QUIN levels were elevated by treatment with its precursor kynurenine, but location of the gold particles remained essentially the same under this condition. Treatment with interferon-gamma increased the number of Golgi bodies, vacuoles and pseudopodia, reflecting the activated state of the cell. Significantly increased numbers of gold particles representing QUIN were detectable in approximately the same location as in the case of kynurenine treatment. Combined treatment with kynurenine and interferon-gamma maximally increased the number of gold particles at the periphery of the cell. The pseudopodia were intensely stained with gold particles, while they were not detectable in the inner part of the cytoplasm or in any other organelle even under this activated condition. The significance of the specific location of QUIN revealed in the present study and its relation to the release and subsequent actions of QUIN are discussed. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Namboodiri, MAA (reprint author), Georgetown Univ, Dept Biol, Reiss Bldg,Room 402,37th & O St NW, Washington, DC 20057 USA. NR 22 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD DEC PY 1997 VL 290 IS 3 BP 633 EP 639 DI 10.1007/s004410050969 PG 7 WC Cell Biology SC Cell Biology GA YM010 UT WOS:000071018400015 PM 9369539 ER PT J AU Clerici, M Sarin, A Henkart, PA Shearer, GM AF Clerici, M Sarin, A Henkart, PA Shearer, GM TI Apoptotic cell death and cytokine dysregulation in human immunodeficiency virus infection: pivotal factors in disease progression SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE apoptosis; programmed cell death; HIV; AIDS; immunology; cytokines; T lymphocytes ID HUMAN MEDULLARY THYMOCYTES; TUMOR-NECROSIS-FACTOR; CD8(+) T-CELLS; HIV-1 INFECTION; FAS ANTIGEN; IMMUNE-SYSTEM; AIDS; LYMPHOCYTES; ACTIVATION; INDIVIDUALS AB The progressive loss of CD4 T lymphocyte is patognomonic of Human Immunodeficiency Virus (HIV) infection and results in immunodeficiency and the appearance of acquired immunodeficiency syndrome (AIDS)-defining pathologies. Although a percentage of CD4 T lymphocytes is destroyed directly by HIV infection, a much higher proportion of lymphocytes remains uninfected and therefore must be destroyed by mechanisms not directly involving viral infection. One such mechanism is apoptotic T cell death (ATCD). ATCD in HIV infection has been shown to be: 1) secondary to cross-linking of CD4 by viral proteins; 2) mediated by both APO-1/Fas and lymphotoxin (LT); and 3) differentially modulated by type 1 and type 2 cytokines. We will briefly analyze the experimental evidences suggesting that ATCD contributes significantly to the immunopathogenesis of HIV/AIDS via depletion of CD4(+) T cells. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MILAN,CATTEDRA IMMUNOL,PADIGLIONE LITA,OSPED L SACCO,I-20154 MILAN,ITALY. NR 80 TC 10 Z9 10 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD DEC PY 1997 VL 4 IS 8 BP 699 EP 706 DI 10.1038/sj.cdd.4400314 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YJ306 UT WOS:A1997YJ30600007 PM 16465282 ER PT J AU Clerici, M Shearer, GM AF Clerici, M Shearer, GM TI Apoptotic T cell death in HIV/AIDS SO CELL DEATH AND DIFFERENTIATION LA English DT Editorial Material C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Clerici, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,I-20122 MILAN,ITALY. NR 3 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD DEC PY 1997 VL 4 IS 8 BP 834 EP 834 DI 10.1038/sj.cdd.4400333 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YJ306 UT WOS:A1997YJ30600021 PM 16465296 ER PT J AU De Santis, ML Kannan, S Smith, GH Seno, M Bianco, C Kim, N Martinez-Lacaci, I Wallace-Jones, B Salomon, DS AF De Santis, ML Kannan, S Smith, GH Seno, M Bianco, C Kim, N Martinez-Lacaci, I Wallace-Jones, B Salomon, DS TI Cripto-1 inhibits beta-casein expression in mammary epithelial cells through a p21(ras) and phosphatidylinositol 3 '-kinase dependent pathway SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; GENE-EXPRESSION; TGF-ALPHA; EXTRACELLULAR-MATRIX; TRANSGENIC MICE; FACTOR RECEPTOR; BREAST-CANCER; DIFFERENTIATION; GLAND; ACTIVATION AB Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor family that does not directly activate any of the known erbB type 1 tyrosine kinase receptors. Also, CR-1 stimulates the growth of HC-11 mouse mammary epithelial cells. We found that prior treatment of HC-11 cells with exogenous DB-1 induced a competency response to the lactogenic hormones dexamethasone, insulin, and prolactin (DIP) with respect to the induction of the milk protein beta-casein. In contrast, simultaneous treatment of mouse HC-11 cells with CR-1 in the presence of DIP inhibited beta-casein expression. The inhibitory effects of CR-1 on p-casein expression in response to DIP were not unique to this mouse mammary epithelial cell line, because beta-casein and whey acidic protein expression in primary mouse mammary explant cultures established from midpregnant mice were also differentially inhibited by several epidermal growth factor-related peptides including CR-1. The mitogenic and differentiation effects of CR-1 are mediated by the binding of CR-1 to a cell surface receptor that is known to activate the ras/raf/mitogen-activated protein kinase (MAPK)/MAPK kinase pathway. The inhibitory response of CR-1 in HC-11 cells on beta-casein expression after treatment with DIP can be attenuated by B581, a peptidomimetic farnesyltransferase inhibitor that blocks p21(ras) farnesylation and activation, and by the phosphatidylinositol 3'-kinase (PI3k) inhibitor LY 294002 but not by PD 98059, a MAPK kinase inhibitor that blocks MAPK activation. These data suggest that the ability of CR-1 to block lactogenic hormone-induced expression of beta-casein is mediated through a p21(ras)-dependent, P13k-mediated pathway. This is further substantiated by the observation that CR-1 is able to stimulate the tyrosine phosphorylation of the p85 PI3k regulatory subunit and to increase the activity of PI3k in HC-11 cells. C1 NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. Okayama Univ, Dept Bioengn Sci, Okayama 700, Japan. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, NIH, Bldg 10,Room 5B39, Bethesda, MD 20892 USA. RI SENO, Masaharu /B-2092-2011 OI SENO, Masaharu /0000-0001-8547-6259 FU NCI NIH HHS [CA-45708] NR 41 TC 38 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1997 VL 8 IS 12 BP 1257 EP 1266 PG 10 WC Cell Biology SC Cell Biology GA YM335 UT WOS:000071053300003 PM 9419414 ER PT J AU Krimer, LS Hyde, TM Herman, MM Saunders, RC AF Krimer, LS Hyde, TM Herman, MM Saunders, RC TI The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans SO CEREBRAL CORTEX LA English DT Article ID RHESUS-MONKEY; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; HIPPOCAMPAL-FORMATION; DENTATE GYRUS; HUMAN-BRAIN; NEURONS; SCHIZOPHRENIA; PROJECTIONS; PATHOLOGY AB The entorhinal cortex (ERC) has been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and other disorders affecting cognitive functions. While powerful anatomical and histochemical methods (immunohistochemistry, in situ hybridization, etc.) may he applied (although with limitations) to postmortem human brain, each analysis should utilize a cytoarchitectonic approach to provide appropriate comparisons within the subdivisions of the ERC. Accordingly, we describe here the normal cyto-and myeloarchitecture of the human ERC as a prerequisite far the accompanying study of this region in schizophrenia. Our parcellation of this cortex differs from previous treatments in three ways. First, we adopted specific criteria of inclusion to define each subdivision of the region. Although distinctive ERC features are most prominent in the intermediate portion of this region, at least one of these features was considered the minimum necessary criterion to include adjacent tissue in the entorhinal area. Second, we used morphometric measurements (neuronal size and density as well as subdivisional volume and laminar thickness) to support our qualitative evaluation. Third, we have applied to the human ERC the conventional cytoarchitectonic nomenclature of the entorhinal cortex used previously in studies of non human primates. This allows a more accurate extrapolation of the available numerous experimental anatomical, physiological and psychological data on this region to the human. As in the monkey, the five main subareas were recognized in the human (prorhinal, lateral, intermediate, sulcal and medial) but three required further subdivision (intermediate, sulcal and medial). The morphometric results obtained suggested a progression of the human entorhinal cortex from the peripheral to the central subareas, with the intermediate subarea (28I) as the most complete entorhinal subdivision. Compared with non human primates, the human ERC not only retains the basic periallocortical organization but also demonstrates further evolution. Taken together with available experimental data on the connectivity of this brain region, these results provide an anatomical basis for evaluating the ERC in human behavior. C1 ST ELIZABETH HOSP, CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,IRP,NIMH, NIH, WASHINGTON, DC 20032 USA. NR 49 TC 40 Z9 41 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 1997 VL 7 IS 8 BP 722 EP 731 DI 10.1093/cercor/7.8.722 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YF085 UT WOS:A1997YF08500003 PM 9408036 ER PT J AU Krimer, LS Herman, MM Saunders, RC Boyd, JC Hyde, TM Carter, JM Kleinman, JE Weinberger, DR AF Krimer, LS Herman, MM Saunders, RC Boyd, JC Hyde, TM Carter, JM Kleinman, JE Weinberger, DR TI A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia SO CEREBRAL CORTEX LA English DT Article ID PARAHIPPOCAMPAL GYRUS; PATHOLOGY; HIPPOCAMPUS; NEURONS; POSTMORTEM; BRAINS; MONKEY; NUMBER; CELLS; SIZE AB The entorhinal cortex (ERC) has been implicated in schizophrenia by a number of studies. There is anatomical observation of neuronal heterotopias in the rostral ERC, which is consistent with a hypothesis of neurodevelopmental abnormalities in this disease. In view of the significant cytoarchitectonic variation of the ERC throughout its rostro-caudal extent, we performed a detailed subareal analysis of the rostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortem schizophrenic brains and 14 matched controls (mean ages of 48 and 47 respectively). This systematic evaluation included both a qualitative microscopic analysis of morphogenetic anomalies that would be consistent with neurodevelopmental pathology and quantitative measurements of total neuronal number, average neuronal density, laminar volume and laminar depth from the cortical surface in cytoarchitectonically matched subareas of schizophrenic and control brains. Parcellation of the entire ERC on the basis of cytoarchitectonic criteria identified five distinct regions, similar to those described in the macaque, except that in the human brain three of the regions were further divisible into two or three subareas, yielding nine distinct cellular compartments. Five rostral areas, prorhinal (Pr), lateral (28L), intermediate rostral and caudal (28Ir and 28Ic), and sulcal (28S), comprise the ERCr. Gross and microscopic examination of these subdivisions throughout the ERCr failed to reveal laminar disorganization in any of the schizophrenic brains. The brains also did not differ significantly with respect to total neuronal number, total volume and neuronal density per laminar and subareal subdivision, or laminar thickness per entorhinal subarea. However, neuronal number and density were reduced by 12-18% in Pr and 28L, suggesting that mild quantitative abnormalities may exist in the ERCr and might possibly be revealed in a larger sample of schizophrenic brains. We have failed to confirm previous reports of laminar disorganization in the ERCr in brains of patients with schizophrenia; to the extent that this region is implicated in schizophrenia, the structural changes are likely to consist of more subtle cellular disturbances. C1 ST ELIZABETHS, CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,IRP,NIMH, NIH, WASHINGTON, DC 20032 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT PATHOL, CHARLOTTESVILLE, VA 22908 USA. OFF CHIEF MED EXAMINER, WASHINGTON, DC 20032 USA. NR 34 TC 70 Z9 70 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 1997 VL 7 IS 8 BP 732 EP 739 DI 10.1093/cercor/7.8.732 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YF085 UT WOS:A1997YF08500004 PM 9408037 ER PT J AU Bertolino, A Saunders, RC Mattay, VS Bachevalier, J Frank, JA Weinberger, DR AF Bertolino, A Saunders, RC Mattay, VS Bachevalier, J Frank, JA Weinberger, DR TI Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: A proton magnetic resonance spectroscopic imaging study SO CEREBRAL CORTEX LA English DT Article ID DELAYED-ALTERNATION; CEREBRAL-CORTEX; MACACA-MULATTA; LOBE LESIONS; IN-VIVO; SCHIZOPHRENIC-PATIENTS; HIPPOCAMPAL-FORMATION; NEURAL MECHANISMS; WORKING-MEMORY; FRONTAL LOBES AB Focal brain damage occurring early in development can have widespread repercussions throughout the developing brain. In living adult rhesus monkeys, we studied the long-term effects of early mesial temporo-limbic (MTL) lesions on prefrontal cortex (PFC) neurons using proton magnetic resonance spectroscopic imaging (H-1-MRSI), an in vivo neurochemical assay technique for measuring signals from metabolites such as N-acetyl-aspartate (NAA, a neuronal marker), choline-containing compounds (CHO) and creatine + phosphocreatine (CRE). Six monkeys (NL) had undergone surgical ablation of MTL structures within 3 weeks of birth, six monkeys received the same lesion at similar to 5 years of age and six monkeys were normal controls. We found significant bilateral reductions of NAA relative signals exclusively in the PFC of the NL group in comparison with either of the other groups. Our results indicate that neonatal MTL damage specifically affects PFC neurons of adult monkeys as indicated by a reduction of NAA. The basis of this effect involves developmental processes as implicated by two arguments: analogous damage during adulthood does not have the same effect; NAA in the healthy brain increases during development. This finding may have implications for understanding developmental aspects of prefrontal-temporolimbic connectivity, and the reduction of NAA levels observed in prefrontal cortex of patients with schizophrenia. C1 ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAMS,NIH,WASHINGTON,DC 20032. UNIV TEXAS,DEPT NEUROBIOL & ANAT,HOUSTON,TX. NIH,LAB DIAGNOST RADIOL RES,OD,BETHESDA,MD. RI Bertolino, Alessandro/O-6352-2016 OI Bertolino, Alessandro/0000-0002-1251-1380 NR 93 TC 85 Z9 85 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 1997 VL 7 IS 8 BP 740 EP 748 DI 10.1093/cercor/7.8.740 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YF085 UT WOS:A1997YF08500005 PM 9408038 ER PT J AU Reszka, KJ Matuszak, Z Chignell, CF AF Reszka, KJ Matuszak, Z Chignell, CF TI Lactoperoxidase-catalyzed oxidation of the anticancer agent mitoxantrone by nitrogen dioxide (NO2 center dot) radicals SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NITRIC-OXIDE; ANTIMICROBIAL ACTIVITY; NUCLEIC-ACIDS; AMETANTRONE; PEROXIDASE; OXYGEN; DNA; MYELOPEROXIDASE; INHIBITION; ACTIVATION AB Mitoxantrone[1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl] amino]-9,10-anthracene-dione, MXH2] is a novel anticancer agent frequently employed in the chemotherapy of leukemia and breast cancer. Earlier studies have shown that metabolic oxidation to reactive 1,4-quinone or/and 5,8-diiminequinone intermediates may be an important mechanism of activation of this agent, pertinent to its cytotoxic action in vivo. Here we report that in the presence of nitrite ions (NO2-), MXH2 undergoes oxidation by the mammalian enzyme lactoperoxidase (LPO) and hydrogen peroxide and that the process proceeds at a rate that is proportional to NO(2)(-)concentration. In contrast, when MXH2 was exposed to LPO/H2O2 in the absence of nitrite, oxidation of the drug was either completely absent or markedly inhibited. These experiments were carried out using concentrated solutions of MXH2 (similar to 100 mu M) at near neutral pH where dimers of the drug predominate. We propose that oxidation of MXH2 is mediated by an LPO/H2O2 metabolite of NO2-; most likely the .NO2 radical. Because in mitoxantrone therapy the drug is administered intravenously, it is directly exposed to nitrogen oxides and other free radicals produced by blood components. It is therefore possible that the ability of mitoxantrone to react with the nitrogen dioxide radical may be relevant to the biological action of the drug in vivo. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Reszka, KJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 24 Z9 24 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 1997 VL 10 IS 12 BP 1325 EP 1330 DI 10.1021/tx970039q PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA YN489 UT WOS:000071173700004 PM 9437521 ER PT J AU Tockman, MS Mulshine, JL Piantadosi, S Erozan, YS Gupta, PK Ruckdeschel, JC Taylor, PR Zhukov, T Zhou, WH Qiao, YL Yao, SX AF Tockman, MS Mulshine, JL Piantadosi, S Erozan, YS Gupta, PK Ruckdeschel, JC Taylor, PR Zhukov, T Zhou, WH Qiao, YL Yao, SX CA Lung Canc Early Detection Work Grp Investigato Yunnan Tin Corp Investigators TI Prospective detection of preclinical lung cancer: Results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; SQUAMOUS-CELL CARCINOMA; 2ND PRIMARY TUMORS; MONOCLONAL-ANTIBODIES; PROTEINS; TRANSLOCATION; LIPOSARCOMA; BINDING; TLS/FUS; CHOP AB The United States lung cancer epidemic has not yet been controlled by present prevention and treatment strategies. Overexpression of a M-r 31,000 protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, had shown promise as a marker of lung cancer. In a pilot study of archived preneoplastic sputum specimens, hnRNP A2/B1 overexpression more accurately detected preclinical lung cancer than standard cytomorphology. In separate, ongoing prospective studies, sputum is collected annually from stage I resected non-small cell lung cancer patients at high risk of developing a second primary lung cancer and Yunnan tin miners at high risk of primary lung cancer. After the first year of follow-up, preclinical detection of lung cancer by routine cytology was compared with hnRNP A2/B1 overexpression as measured by quantitative densitometry of immunostained slides. Up-regulation of hnRNP A2/B1 in sputum specimens accurately predicted the outcome in 32 of 40 primary lung cancer and control patients within 12 months, whereas cytological change suggestive of lung cancer was found in only 1 patient. In the primary lung cancer study, overexpressed hnRNP A2/B1 accurately predicted the outcome in 69 of 94 primary lung cancer and control miners, whereas only 10 with primary lung cancer were diagnosed cytologically. These two prospective studies accurately predicted that 67 and 69% of those with hnRNP A2/B1 upregulation in their sputum would develop lung cancer in the first year of follow-up, compared with background lung cancer risks of 2.2 and 0.9% (35- and 76-fold increase, respectively). Using sputum cells to monitor hnRNP A2/B1 expression may greatly improve the accuracy of preclinical lung cancer detection. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NCI, Cell & Canc Biol Dept, Med Branch, Div Clin Sci, Rockville, MD USA. NCI, Div Canc Prevent & Control, Canc Prevent Studies Branch, Rockville, MD USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Yunnan Tin Corp, Lab Protect Inst, Gejiu City, Peoples R China. RP Tockman, MS (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU NCI NIH HHS [1P50 CA58184-01, CNZ-5420-00, ECOG E5593] NR 58 TC 134 Z9 142 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1997 VL 3 IS 12 BP 2237 EP 2246 PN 1 PG 10 WC Oncology SC Oncology GA YM012 UT WOS:000071018600008 PM 9815620 ER PT J AU Marshall, JL Wellstein, A Rae, J DeLap, RJ Phipps, K Hanfelt, J Yunmbam, MK Sun, JX Duchin, KL Hawkins, MJ AF Marshall, JL Wellstein, A Rae, J DeLap, RJ Phipps, K Hanfelt, J Yunmbam, MK Sun, JX Duchin, KL Hawkins, MJ TI Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID FIBROBLAST GROWTH-FACTOR; COMPETITIVE-BINDING ASSAY; HUMAN-ENDOTHELIAL CELLS; SULFATED POLYSACCHARIDES; PRENEOPLASTIC LESIONS; INTERSTITIAL CYSTITIS; TUMOR ANGIOGENESIS; FACTOR FAMILY; HEPARIN; PENTOSANPOLYSULFATE AB Tumor angiogenesis is critically important to tumor growth and metastasis. We have shown that pentosan polysulfate (PPS) is an effective inhibitor of heparin-binding growth factors in vitro and can effectively inhibit the establishment and growth of tumors in nude mice. Following completion of our Phase I trial of s.c. administered PPS, we performed a Phase I trial of p.o. administered PPS in patients with advanced cancer to determine the maximum tolerated dose (MTD) and toxicity profile and to search for any evidence for biological activity in vivo. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m(2). Patients were monitored at least every 2 weeks with physical exams and weekly with hematological, chemistry, stool hemoccult, and coagulation blood studies, and serum and urine samples for PPS and basic fibroblastic growth factor (bFGF) levels were also taken. The PPS dose was escalated in an attempt to reach the MTD. Eight additional patients were enrolled at the highest dose to further characterize the toxicity profile and biological in vivo effects of PPS. A total of 21 patients were enrolled in the three cohorts of doses 180 (n = 4), 270 (n = 3), and 400 (n = 14) mg/m(2). The most severe toxicities seen were grade 3 proctitis and grade 4 diarrhea; however, 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels. There were no objective responses, although three patients had prolonged stabilization of previously progressing disease. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration. Serum and urine bFGF levels failed to show a consistent, interpretable pattern; however the data suggested an inverse relationship between PPS and bFGF levels in vivo. A MTD could not be determined using the daily t.i.d. dosing schedule due to the development of grade 3/4 GI toxicity (proctitis) at all dose levels studied. PPS, administered p.o. at doses of 400 mg/m(2) t.i.d., did not cause significant systemic toxicity, but most patients developed moderate-to-severe GI toxicity within 1-2 months. The cause of the GI toxicity was unclear, but it was readily reversible upon cessation of the agent. The suggestion of an inverse relationship between PPS and bFGF supports further study of PPS as an antiangiogenic agent. The tested doses and schedule cannot be recommended for further study. Subsequent murine experiments showed PPS to be more effective as an anticancer agent when it is given intermittently. We propose a study of PPS given on a weekly schedule in further clinical trials. C1 Georgetown Univ Hosp, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Baker Norton Pharmaceut Inc, Miami, FL USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20854 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Marshall, JL (reprint author), Georgetown Univ Hosp, Vincent T Lombardi Canc Res Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA. OI Wellstein, Anton/0000-0002-0570-4950 FU NCI NIH HHS [5 UO1 CA62500] NR 46 TC 36 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1997 VL 3 IS 12 BP 2347 EP 2354 PN 1 PG 8 WC Oncology SC Oncology GA YM012 UT WOS:000071018600021 PM 9815633 ER PT J AU Wosikowski, K Schuurhuis, D Kops, GJPL Saceda, M Bates, SE AF Wosikowski, K Schuurhuis, D Kops, GJPL Saceda, M Bates, SE TI Altered gene expression in drug-resistant human breast cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROGNOSTIC-SIGNIFICANCE; ADRIAMYCIN-RESISTANT; SIGNAL-TRANSDUCTION; TOPOISOMERASE-II; CARCINOMA CELLS; MCF-7 CELLS; PROTEIN; INVITRO; LINE AB It is increasingly recognized that drug-resistant cells undergo transitions not directly linked to "classical" drug resistance, We examined the expression of growth factors, growth factor receptors, and the estrogen receptor in 17 drug-resistant and 2 revertant human breast cancer sublines to provide an understanding of the phenotypic changes that occur and how these changes could affect the biology of the cell, These sublines were derived from five parental human breast cancer cell lines (MCF-7, ZR75B, T47D, MDA-MB-231, and MDA-MB-453). The expression of estrogen receptor was absent or decreased in 6 of the 15 resistant MCF-7. ZR75B, and T47D sublines, Increases of as much as 49-fold compared to parental levels were observed in transforming growth factor alpha, epidermal growth factor receptor, c-erbB2, and/or c-erbB3 mRNA expression in 14 of the 17 resistant sublines, Altered amphiregulin and insulin-like growth factor-I receptor expression was observed in nine and four drug-resistant sublines, respectively, No major alterations were observed in epidermal growth factor and c-erbB4 expression, Few alterations were observed in two sublines derived from estrogen receptor-negative cells, Higher levels of phosphotyrosine residues were detected in a subset of the resistant sublines, indicating an increased tyrosine kinase activity in these cells, Interestingly, decreased growth rates were observed in all of the sublines, despite up-regulated growth factor-related gene expression, Taken together, these data suggest that loss of estrogen receptor, increased expression of growth factor pathway genes, and decreased growth rate regularly occur in drug-resistant breast cancer cells. Although we do not know whether the altered expression of growth factor pathway genes is linked as a cause or a consequence of the reduced growth rate, it is well established that decreased growth rate confers drug resistance, These phenotypic changes in drug-resistant human breast cancer cells could serve to initiate, support, or extend the drug resistance. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20982 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Bates, SE (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20982 USA. RI Saceda, Miguel/A-1581-2008 NR 58 TC 61 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1997 VL 3 IS 12 BP 2405 EP 2414 PN 1 PG 10 WC Oncology SC Oncology GA YM012 UT WOS:000071018600029 PM 9815641 ER PT J AU Tsang, KY Zhu, MZ Nieroda, CA Correale, P Zaremba, S Hamilton, JM Cole, D Lam, C Schlom, J AF Tsang, KY Zhu, MZ Nieroda, CA Correale, P Zaremba, S Hamilton, JM Cole, D Lam, C Schlom, J TI Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN REGRESSIVE MELANOMA; RECOMBINANT VACCINIA-CEA; ANTITUMOR-ACTIVITY; MULTIPLE EPITOPES; IN-VITRO; PEPTIDE; RECOGNITION; GENE; VIRUS AB CTL lines have now been generated against defined peptides of a range of human tumor-associated antigens (TAAs), One of the potential uses of these epitope-specific CTLs is in adoptive transfer immunotherapy. This is a modality, however, that will require long-term in vitro culture of CTLs, To date, little has been reported concerning the phenotypic stability of human epitope-specific CTLs as a consequence of long-term in vitro propagation via peptide stimulation, We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA), This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells, The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner, V beta T-cell receptor gene usage was also analyzed, These studies thus present a rationale for the use of longterm cultured epitope-specific human CTLs, directed against a human TAA for potential adoptive transfer immunotherapy protocols. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Navy Med Oncol Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 8B07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Correale, Pierpaolo/K-1640-2016 OI Correale, Pierpaolo/0000-0003-2154-6734 NR 53 TC 60 Z9 61 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1997 VL 3 IS 12 BP 2439 EP 2449 PN 1 PG 11 WC Oncology SC Oncology GA YM012 UT WOS:000071018600033 PM 9815645 ER PT J AU Oppenheim, JJ Murphy, WJ Chertov, O Schirrmacher, V Wang, JM AF Oppenheim, JJ Murphy, WJ Chertov, O Schirrmacher, V Wang, JM TI Prospects for cytokine and chemokine biotherapy SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Foundations of Clinical Cancer Research - Perspective for the 21st-Century CY MAR 14-15, 1997 CL HOUSTON, TEXAS ID ANTITUMOR IMMUNITY; CARCINOMA-CELLS; BETA RECEPTOR; IN-VIVO; TUMOR; EXPRESSION; INDUCTION; MELANOMA; GROWTH; INTERLEUKIN-1-ALPHA AB Cytokines with immunostimulating effects have the capacity to induce tumor immunity in animal models, whereas some cytokines interfere with tumor growth based on their angiostatic effects, Despite these capabilities, cytokines, such as IFN-alpha, IFN-gamma, tumor necrosis factor, interleukin (IL)-1, and IL-2, have had limited clinical efficacy and many undesirable side effects, In preclinical models, cytokines can even promote tumor growth and increase metastatic spread, Although chemokines have had limited clinical evaluation, studies of animal models show that they can also have tumor-suppressive or tumor-enhancing effects, In mice, chemokines, such as IP-10, RANTES, and TCA3, have resulted in tumor regression and immunity to subsequent tumor challenge, Those chemokines that are angiostatic (e.g., PF4, IP-10, and MIC) can also induce tumor regression by reducing the tumor blood supply, Conversely, IL-8, which is angiogenic, can promote tumor growth, Our studies show that nasopharyngeal cell line cells (FADU) show a chemotactic as well as a proliferative response to MCP-1, In addition, a variant murine T cell lymphoma cell line Esb-MP, unlike the parental variant Esb, was selectively chemoattracted by murine MCP-1/JE, When injected s.c. into mice, the Esb MP variant metastasized to the kidney with much higher frequency than the Esb variant, Both cultured kidneys from normal mice and a mesangial cell line constitutively produced chemoattractants that acted on Esb-MP but not Esb parental cells, Purification to homogeneity of these chemoattractants led to the identification of RANTES and JE, These results demonstrate that some chemokines may promote tumor growth and organ-specific metastatic spread of those tumors that have adapted and become responsive to chemokines. Finally, tumors appear to use numerous adaptive mechanisms to subvert and suppress the immune system, More effective therapy with cytokines and chemokines will require better characterization of the means by which tumors develop resistance to cytokines and overcome the immune system. Only then can we develop appropriate therapeutic approaches to antagonize cancer-induced immunosuppression. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Appl Int Corp Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. German Canc Inst, D-69120 Heidelberg, Germany. RP Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. NR 36 TC 36 Z9 37 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1997 VL 3 IS 12 BP 2682 EP 2686 PN 2 PG 5 WC Oncology SC Oncology GA YN137 UT WOS:000071136800024 PM 10068274 ER PT J AU Welsh, JA Castren, K Vahakangas, KH AF Welsh, JA Castren, K Vahakangas, KH TI Single-strand conformation polymorphism analysis to detect p53 mutations: characterization and development of controls SO CLINICAL CHEMISTRY LA English DT Article ID CARCINOMA CELL-LINES; POINT MUTATIONS; GEL-ELECTROPHORESIS; SSCP ANALYSIS; LUNG-CANCER; BREAST-CANCER; HUMAN TUMORS; PCR-SSCP; GENE; DNA AB Single-strand conformation polymorphism (SSCP) analysis is widely used to prescreen mutations in p53 gene. However, standardization of SSCP to detect p53 mutations has rarely been pursued so far. We have developed complete conditions for a temperature-controlled nonradioactive SSCP for mutation detection in amplified p53 exons 4-8, where mutations frequently occur in human tumors. Easily obtainable and clearly distinguishable positive controls were developed by replacing the regular 5' primers in amplification with primers that include one to three mutated sites. Careful purification of the amplified products by gel electrophoresis appeared to be essential. The efficiency of the method was studied by using previously sequenced samples with p53 mutations and the various positive controls. The use of two temperatures (exon 4: 4 degrees C and 15 degrees C; other exons: 4 degrees C and 20 degrees C) in combination with other optimized conditions resulted in 98% efficiency in mutation detection, which was considered sufficient for routine screening. C1 Univ Oulu, Dept Pharmacol & Toxicol, FIN-90220 Oulu, Finland. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Vahakangas, KH (reprint author), Univ Oulu, Dept Pharmacol & Toxicol, FIN-90220 Oulu, Finland. NR 32 TC 25 Z9 28 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 1997 VL 43 IS 12 BP 2251 EP 2255 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YN107 UT WOS:000071133800005 PM 9439440 ER PT J AU Rich, KC Brambilla, D Pitt, J Moye, J Cooper, E Hillyer, G Mendez, H Fowler, MG Landay, A AF Rich, KC Brambilla, D Pitt, J Moye, J Cooper, E Hillyer, G Mendez, H Fowler, MG Landay, A TI Lymphocyte phenotyping in infants: Maturation of lymphocyte subpopulations and the effects of HIV infection SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ZIDOVUDINE TREATMENT; CELL ACTIVATION; T-CELLS; PROGNOSTIC VALUE; CLINICAL-TRIALS; FLOW-CYTOMETRY; AIDS PATIENTS; CHILDREN; SUBSETS AB Changes in the distribution of lymphocyte subpopulations in infants with perinatally acquired HIV infection are confounded by the rapid changes that are the result of normal maturation of the immune system. We describe the changes in seven lymphocyte phenotypes (CD3+CD4+, CD3+CD8+, CD8+HLA-DR+, CD8+CD38+, CD8+CD57+, CD3-CD16+56+, and CD19+) over the first 2 years of life in 390 HIV-1 exposed but uninfected and 98 HIV-1-infected infants enrolled in the Women and Infants Transmission Study. The greatest changes in uninfected infants were declines in the CD3+CD4+ lymphocytes and increases in CD8+HLA-DR+ and CD19+ lymphocytes. All phenotypes were affected by HIV infection but the greatest change's were declines in the CD3+CD4+ subset and increases in the CD3+CD8+ and CD8+HLA-DR+ subsets. Thus, this study provides reference data for the maturational changes in lymphocyte phenotypes in HIV-exposed but uninfected infants and describes the overall changes that occur with perinatally acquired HIV infection. (C) 1997 Academic Press. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. COLUMBIA UNIV,COLL MED,NEW YORK,NY. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD. BOSTON CITY HOSP,BOSTON,MA 02118. UNIV PUERTO RICO,SCH MED,SAN JUAN,PR 00936. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. NIAID,DIV AIDS,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP Rich, KC (reprint author), UNIV ILLINOIS,DEPT PEDIAT,840 S WOOD ST,MC 856,CHICAGO,IL 60612, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-34856, AI-34842, AI-34858] NR 37 TC 20 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD DEC PY 1997 VL 85 IS 3 BP 273 EP 281 DI 10.1006/clin.1997.4439 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA YH967 UT WOS:A1997YH96700006 PM 9400627 ER PT J AU Green, SB AF Green, SB TI The advantages of community-randomized trials for evaluating lifestyle modification SO CONTROLLED CLINICAL TRIALS LA English DT Article; Proceedings Paper CT 8th International Symposium on Long-Term Clinical Trials CY SEP 28-29, 1995 CL TORONTO, CANADA DE intervention studies; random allocation; randomized controlled trials; smoking cessation; statistics ID VITAMIN-A SUPPLEMENTATION; INTERVENTION TRIALS; CLINICAL-TRIALS; RURAL TANZANIA; DESIGN; IMPACT; CLUSTER; UNIT AB Observational studies may provide suggestive evidence for the results of behavior change and lifestyle modification, but they do not replace randomized trials for comparing interventions. To obtain a valid comparison of competing intervention strategies, randomized trials of adequate size are the recommended approach. Randomization avoids bias, achieves balance (on average) of both known and unknown predictive factors between intervention and comparison groups, and provides the basis of statistical tests. The value of randomization is as relevant when investigating community interventions as it is for studies that are directed at individuals, Randomization by group is less efficient statistically than randomization by individual, but there are reasons why randomization by group (such as community) may be chosen, including feasibility of delivery of the intervention, political and administrative considerations, avoiding contamination between individuals allocated to competing interventions, and the very nature of the intervention. One example is the Community Intervention Trial for Smoking Cessation (COMMIT), which involved 11 matched pairs of communities and randomized within these pairs to active community-level intervention versus comparison. For analysis of results, community-level permutation tests (and corresponding test-based confidence intervals) can be designed based on the randomization distribution. The advantages of this approach are that it is robust, and the unit of randomization is the unit of analysis, yet it can incorporate individual-level covariates. Such covariates can play a role in imputation for missing values, adjustment for imbalances,and separate analyses in demographic subsets (with appropriate tests for interaction). A community-randomized trial can investigate a multichannel community-based approach to lifestyle modification, thus providing generalizability coupled with, a rigorous evaluation of the intervention. Published by Elsevier Science Inc. 1997. RP Green, SB (reprint author), NCI,EXECUT PLAZA N,SUITE 344,6130 EXECUT BLVD,MSC 735,BETHESDA,MD 20892, USA. NR 21 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1997 VL 18 IS 6 BP 506 EP 513 DI 10.1016/S0197-2456(97)00013-5 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA YH968 UT WOS:A1997YH96800006 PM 9408714 ER PT J AU Slonim, AD Patel, KM Ruttimann, UE Pollack, MM AF Slonim, AD Patel, KM Ruttimann, UE Pollack, MM TI Cardiopulmonary resuscitation in pediatric intensive care units SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Pediatric Academic Societies CY MAY 02-06, 1997 CL WASHINGTON, DC DE cardiopulmonary resuscitation; cardiac arrest; pediatric; pediatric intensive care unit; outcomes; effectiveness; Pediatric Risk of Mortality III scores; severity of illness ID MORTALITY; CHILDREN; ARREST; SCORE; RISK AB Objective: To determine the effectiveness of cardiopulmonary rescucitation (CPR) in the pediatric intensive care unit (ICU). Design: A nonconcurrent cohort study of consecutive admissions, Setting: Thirty-two pediatric ICUs, Patients: Consecutive admissions to 32 pediatric ICUs, interventions: None, Measurements and Main Results: Pediatric ICU patients were followed for the occurrence of a cardiopulmonary arrest (external cardiac massage for at least 2 mins), Patients who were in a state of continuous cardiopulmonary arrest on admission, or who never achieved stable vital signs, were excluded from the study, A total of 205 patients, from a sample of 11,165 (1.8%) pediatric admissions, experienced a cardiopulmonary arrest. Overall, 28 (13.7%) patients survived to hospital discharge, Neither mean ages nor age distribution affected survival, Only two diagnostic categories, traumatic illness, and other etiologies, were associated with survival. None of the patients fitting this category survived (p=.0028), The durations of CPR for survivors and nonsurvivors were 22.5 +/- 10.1 and 24.8 +/- 1.9 mins, respectively (p=.015), For CPR durations of <15 mins, 15 to 30 mins, and >30 mins, the survival rates were 18.6%, 12.2%, and 5.6%, respectively (linear trend p=.022), Thirty-five (17.1%) patients had a cardiopulmonary arrest before pediatric ICU admission and another arrest in the pediatric ICU. Only two (5.7%) of these 35 patients survived to discharge. Pediatric ICU survival decreased as the number of pediatric ICU arrests increased. Patients with one arrest (n = 155), two arrests (n = 29), and more than three arrests (n = 21) experienced survival rates of 14%, 14%, and 9.5%, respectively, Severity of illness, as measured by the Pediatric Risk of Mortality III score, was a significant predictor of survival (p<.001). Conclusions: Pediatric ICU cardiac arrest is an uncommon event, When it does occur, prehospital CPR, duration of resuscitation, traumatic etiology, and severity of illness are important factors associated with survival. C1 CHILDRENS NATL MED CTR,DEPT CRIT CARE MED,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. NIH,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,WASHINGTON,DC. CHILDRENS RES INST,CTR HLTH SERV & CLIN RES,WASHINGTON,DC. FU PHS HHS [MCH-110584] NR 26 TC 109 Z9 110 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 1997 VL 25 IS 12 BP 1951 EP 1955 DI 10.1097/00003246-199712000-00008 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA YK746 UT WOS:A1997YK74600008 PM 9403741 ER PT J AU Aman, NJ Leonard, WJ AF Aman, NJ Leonard, WJ TI Cytokine signaling: Cytokine-inducible signaling inhibitors SO CURRENT BIOLOGY LA English DT Article AB Seven members of a family of cytokine-inducible proteins have been identified, a number of which have been shown to act as negative regulators of cytokine action, All of these proteins contain a central Src homology 2 domain, as well as conserved motifs in their carboxy-terminal regions. RP Aman, NJ (reprint author), NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20893, USA. NR 7 TC 0 Z9 0 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 DEC 1 PY 1997 VL 7 IS 12 BP R784 EP R788 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YL440 UT WOS:A1997YL44000018 ER PT J AU Wolffe, AP AF Wolffe, AP TI Transcription control: Repressed repeats express themselves SO CURRENT BIOLOGY LA English DT Article ID GENE; DROSOPHILA AB Multi copy transgenes are poorly expressed in plants, Drosophila and mammals; this repression is relieved by reducing copy number, leading to chromatin remodeling and transcriptional activation, Host defense mechanisms monitor repeated sequences in the genome, modulating their chromatin packaging and functional capabilities. RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 10 TC 10 Z9 12 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 DEC 1 PY 1997 VL 7 IS 12 BP R796 EP R798 DI 10.1016/S0960-9822(06)00408-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YL440 UT WOS:A1997YL44000021 PM 9382833 ER PT J AU Verma, MJ Lloyd, A Rager, H Strieter, R Kunkel, S Taub, D Wakefield, D AF Verma, MJ Lloyd, A Rager, H Strieter, R Kunkel, S Taub, D Wakefield, D TI Chemokines in acute anterior uveitis SO CURRENT EYE RESEARCH LA English DT Article DE aqueous humor; chemokines; inflammation; uveitis ID ENDOTOXIN-INDUCED UVEITIS; TUMOR-NECROSIS-FACTOR; AQUEOUS-HUMOR; CHEMOTACTIC CYTOKINES; RHEUMATOID-ARTHRITIS; EXPRESSION; INTERLEUKIN-6; RANTES; RAT; CHEMOATTRACTANT AB Purpose. The aim of this study was to define the expression of chemoattractant cytokines (chemokines) in human aqueous humor, obtained from patients with idiopathic acute anterior uveitis (AU). The chemokines assayed included macrophage inflammatory proteins-1 alpha and -1 beta (MLP-1 alpha and -1 beta), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interferon-inducible protein-10 (IP-10), and regulated on activation, normal T-expressed and secreted (RANTES). Methods. We studied fifteen patients (7 females) with idiopathic acute AU, at various stages of disease activity, and two control subjects undergoing elective cataract extraction, Aqueous humor was collected under aseptic conditions, after obtaining informed consent. Chemokine concentrations were measured using specific ELISA. Correlation was sought between chemokine concentrations and disease activity, evaluated by slit lamp biomicroscopy and graded using a standardized scale of disease severity. Results. IL-8 was detected (35.9 +/- 13.6, mean +/- SE) in thrre of seven subjectes in active, untreated stages of AU (clinical score 2-4), and it was undetectable in subjects sampled in the quiescent phase of the disease. IP-10 had a mean concentration of 40.6 ng/ml +/- 20.9 in the active group (N = 7), declining to 0.8 ng/ml +/- 0.3 in the samples from patients with inactive disease (N = 7, P = 0.001). Similarly, substantial expression of MCP-1 was noted, with a maximum concentration of 145 ng/ml, in acute (active) AU (N = 6), (26.7 +/- 19.7), falling to undetectable levels in those with inactive disease, and in control subjects (P = 0.001). MIP-1 beta (N = 7), (3.3 +/- 1.5, P = 0.001) and RANTES (N = 7, 8.8 +/- 4.2) levels were significantly increased in acute disease (P = 0.001) and related to the activity of the disease, although the concentrations were not as high as MCP-1, IP-10 and IL-8. IF-10, RANTES and MIP-1 beta were detected at low concentrations in the aqueous humor of the control subjects. Conclusions. This is the first study of chemokine concentrations in the aqueous humor of patients with acute anterior uveitis. The concentration of chemokines: IL-8, IP-IO, MCP-1, RANTES and MIP-1 beta were significantly increased during the active stages of AU, and correlated with the clinical severity of the disease. These chemoattractant cytokines probably play a critical role in leucocyte recruitment in acute AU. C1 UNIV NEW S WALES,SCH PATHOL,INFLAMMAT RES UNIT,LAB OCULAR IMMUNOL,SYDNEY,NSW 2052,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,SAIC,CYTOKINE TESTING LAB,FREDERICK,MD. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. NR 39 TC 92 Z9 96 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD DEC PY 1997 VL 16 IS 12 BP 1202 EP 1208 DI 10.1076/ceyr.16.12.1202.5034 PG 7 WC Ophthalmology SC Ophthalmology GA YK169 UT WOS:A1997YK16900004 PM 9426952 ER PT J AU Koonin, EV Galperin, MY AF Koonin, EV Galperin, MY TI Prokaryotic genomes: the emerging paradigm of genome-based microbiology SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID ESCHERICHIA-COLI; HAEMOPHILUS-INFLUENZAE; BACTERIAL GENOMES; SEQUENCE; EVOLUTION; LIFE; PROTEINS; GENES AB Comparative analysis of the complete sequences of seven bacterial and three archaeal genomes leads to the first generalizations of emerging genome-based microbiology. Protein sequences are, generally, highly conserved, with similar to 70% of the gene products in bacteria and archaea containing ancient conserved regions. In contrast, there is little conservation of genome organization, except far a few essential operons. The most striking conclusions derived by comparison of multiple genomes from phylogenetically distant species are that the number of universally conserved gene families is very small and that multiple events of horizontal gene transfer and genome fusion are major forces in evolution. (C) Current Biology Ltd ISSN 0959-437X. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM Koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 52 TC 105 Z9 106 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1997 VL 7 IS 6 BP 757 EP 763 DI 10.1016/S0959-437X(97)80037-8 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA YU605 UT WOS:000071734800003 PM 9468784 ER PT J AU Wang, J Lenardo, MJ AF Wang, J Lenardo, MJ TI Molecules involved in cell death and peripheral tolerance SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INTERLEUKIN-1-BETA CONVERTING-ENZYME; DOMAIN-CONTAINING RECEPTOR; FACTOR-INDUCED APOPTOSIS; LPR MICE; LYMPHOPROLIFERATIVE SYNDROME; ICE/CED-3 PROTEASE; FAS/APO-1 CD95; FAS LIGAND AB Apoptosis is important far maintaining peripheral lymphocyte homeostasis and for minimizing the accumulation of autoreactive lymphocytes. Disruption of apoptotic pathways has been linked to lymphadenopathy, breakdown of peripheral tolerance and the development of autoimmune diseases. Major progress has been made during the past year in understanding the critical roles of a variety of signaling molecules, especially a group of cysteine proteases, for the execution of apoptosis. These proteases appear to be the primary effector molecules responsible for carrying out lymphocyte apoptosis and may be critical for peripheral immunological tolerance. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, J (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11D09,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 91 TC 33 Z9 33 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1997 VL 9 IS 6 BP 818 EP 825 DI 10.1016/S0952-7915(97)80184-7 PG 8 WC Immunology SC Immunology GA YW017 UT WOS:000071887300009 PM 9492984 ER PT J AU Groll, AH Walsh, TJ AF Groll, AH Walsh, TJ TI Potential new antifungal agents SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID LIPOSOME-ENCAPSULATED NYSTATIN; IN-VITRO; CANDIDA-ALBICANS; SYNERGISTIC ACTION; ORAL TRIAZOLE; BENANOMICIN-A; NIKKOMYCIN-X; VIVO; ANTIBIOTICS; PRADIMICIN AB The increasing incidence of both mucosal and invasive fungal infections has led to the development of several new systemic antifungal agents. Potent and broad spectrum, third generation triazoles, echinocandins and pneumocandins, fungicidal inhibitors of 1,3-beta glucan synthase, and a liposomal formulation of nystatin have recently entered early clinical trials. Other promising agents with novel targets currently under investigation include the pradimicin family of antibiotics, nikkomycin Z, and perhaps, antimicrobial peptides. Immunomodulation by recombinant cytokines has been extensively studied in the laboratory, and effective antifungal vaccines are on the horizon. In conjuction with currently available agents, including the lipid formulations of amphotericin B, this expanded antifungal armamentarium holds promise to meet the evolving challenges of both invasive and mucosal fungal infections. C1 NCI,IMMUNOCOMPROMISED HOST SECT,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. NR 124 TC 27 Z9 27 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 1997 VL 10 IS 6 BP 449 EP 458 DI 10.1097/00001432-199712000-00007 PG 10 WC Infectious Diseases SC Infectious Diseases GA YH380 UT WOS:A1997YH38000007 ER PT J AU Fowler, MG AF Fowler, MG TI Update: transmission of HIV-1 from mother to child SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; VERTICAL TRANSMISSION; TO-CHILD; ZIDOVUDINE TREATMENT; BREAST-MILK; VIRAL LOAD; TYPE-1; RISK; INFANT; DNA AB Mother-to-child transmission near the time of birth is the primary route of HIV-1 infection among infants and young children. Throughout the world, 1000 babies a day become infected with HIV, and cumulative global estimates are that 3 million children have been infected since the HIV pandemic began. Although major advances have been made in reducing mother-to-child transmission of HIV-1 in the USA and Europe through the use of an intensive regimen of zidovudine, many research questions remain unresolved. These include (1) viral and host characteristics which hinder or facilitate perinatal HIV transmission (i.e. the role played by viral load, the placenta and obstetric risk factors); (2) the proportion of transmission occurring in utero, intrapartum or during the breast feeding period; and (3) the mode of action of the successful zidovudine regimen. Studies published within the past year have shed light on several of these research topics. In 1996-1997 a number of important studies were published which support a general correlation between maternal viral load and infant HIV infection. The most recent studies do not, however, support the theory that there is a threshold below which transmission cannot occur, and also indicate that zidovudine, given according to the US Public Health Service guidelines, can significantly reduce the risk of transmission across all levels of maternal viral load. Analyses of viral load data from the successful clinical trial with zidovudine (AIDS Clinical Trial Group 076) suggest that its primary action is not by reducing the viral load, and raise the possibility that administering antiretroviral prophylaxis to the infant at the time of highest exposure may be another reason for the reduction in transmission. Obstetric risk factors for mother-to-child HIV transmission have been evaluated in several large cohort studies. A duration of membrane rupture of more than 4 h, and procedures such as amniocentesis, preterm labor, and the presence of sexually transmitted diseases during pregnancy were found to be significant risk factors. Still unresolved is the potential protective effect of cesarean section in reducing the risk of transmission. Likewise, the role played by the placenta in preventing or facilitating perinatal transmission is not well understood, and requires further research. This year did see the publication of consistent findings from diverse geopraphical regions regarding the probable timing of perinatal HIV transmission. On the basis of the timing of the first infant positive polymerase chain reaction or culture, most transmission would appear to occur around the intrapartum or very late prenatal period, and only approximately 12-14% is related to breast feeding. These advances should help focus and refine future research efforts to reduce mother-to-child HIV transmission worldwide. RP Fowler, MG (reprint author), NIAID,EFFICACY TRIALS BRANCH,DIV AIDS,NIH,ROOM 2A09,SOLAR BLDG,6003 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 33 TC 1 Z9 1 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 1997 VL 10 IS 6 BP 496 EP 501 DI 10.1097/00001432-199712000-00016 PG 6 WC Infectious Diseases SC Infectious Diseases GA YH380 UT WOS:A1997YH38000016 ER PT J AU Miles, FA AF Miles, FA TI Visual stabilization of the eyes in primates SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID OCULAR-FOLLOWING RESPONSES; HUMAN OPTOKINETIC NYSTAGMUS; DORSOLATERAL PONTINE NUCLEUS; VIEWING DISTANCE; CHEMICAL LESIONS; NEURAL ACTIVITY; ALERT MONKEY; MOTION; LATENCY; DEPENDENCE AB Observers moving through a textured three-dimensional world experience potentially confusing patterns of optic flow. Recent experiments on monkeys and humans have revealed the existence of rapid, yet cortically mediated, reflex eye movements that automatically single out images in the plane of fixation for stabilization and ignore images that are nearer or further. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Room 2A50,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. EM fam@lsr.nei.nih.gov NR 39 TC 24 Z9 24 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD DEC PY 1997 VL 7 IS 6 BP 867 EP 871 DI 10.1016/S0959-4388(97)80148-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA YU905 UT WOS:000071768200014 PM 9464972 ER PT J AU Pilotte, NS AF Pilotte, NS TI Neurochemistry of cocaine withdrawal SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID DOPAMINE TRANSPORTER BINDING; RAT NUCLEUS-ACCUMBENS; RECEPTOR MUTANT MICE; IMMEDIATE-EARLY GENE; BEHAVIORAL SENSITIZATION; NEUROTENSIN BINDING; STRIATUM; BRAIN; EXPRESSION; DYNORPHIN AB Neural circuits comprised of dopamine-containing and dopamine-receptive neurons are altered functionally after the repeated intermittent administration of cocaine and its withdrawal. The characterization of these neuroadaptive changes at various times after repeated exposure to cocaine is important because they may relate to addictive or withdrawal states associated with cocaine abuse. They also may suggest targets leading to the development of medications to treat one or more aspects of cocaine dependence. (C) Rapid Science Publishers. C1 NIDA, Div Basic Res, Rockville, MD 20857 USA. RP Pilotte, NS (reprint author), NIDA, Div Basic Res, 5600 Fishers Lane,Rm 10A-19, Rockville, MD 20857 USA. NR 36 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 1997 VL 10 IS 6 BP 534 EP 538 DI 10.1097/00019052-199712000-00017 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YQ035 UT WOS:000071340900017 PM 9425570 ER PT J AU Fowler, MG AF Fowler, MG TI Update: Transmission of HIV-1 from mother to child SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VERTICAL TRANSMISSION; TO-CHILD; ZIDOVUDINE TREATMENT; BREAST-MILK; VIRAL LOAD; TYPE-1; RISK; INFANT; DNA AB Mother-to-child transmission near the time of birth is the primary route of HIV-1 infection among infants and young children. Throughout the world, 1000 babies a day become infected with HIV, and cumulative global estimates are that 3 million children have been infected since the HIV pandemic began. Although major advances have been made in reducing mother-to-child transmission of HIV-1 in the USA and Europe through the use of an intensive regimen of zidovudine, many research questions remain unresolved. These include (1) viral and host characteristics which hinder or facilitate perinatal HIV transmission (i.e. the role played by viral load, the placenta and obstetric risk factors); (2) the proportion of transmission occurring in utero, intrapartum or during the breast feeding period; and (3) the mode of action of the successful zidovudine regimen. Studies published within the past year have shed light on several of these research topics. In 1996-1997 a number of important studies were published which support a general correlation between maternal viral load and infant HIV infection. The most recent studies do not, however, support the theory that there is a threshold below which transmission cannot occur, and also indicate that zidovudine, given according to the US Public Health Service guidelines, can significantly reduce the risk of transmission across all levels of maternal viral load. Analyses of viral load data from the successful clinical trial with zidovudine (AIDS Clinical Trial Group 076) suggest that its primary action is not by reducing the viral load, and raise the possibility that administering antiretroviral prophylaxis to the infant at the time of highest exposure may be another reason for the reduction in transmission. Obstetric risk factors for mother-to-child HIV transmission have been evaluated in several large cohort studies. A duration of membrane rupture of more than 4 h, and procedures such as amniocentesis, preterm labor, and the presence of sexually transmitted diseases during pregnancy were found to be significant risk factors. Still unresolved is the potential protective effect of cesarean section in reducing the risk of transmission. Likewise, the role played by the placenta in preventing or facilitating perinatal transmission is not well understood, and requires further research. This year did see the publication of consistent findings from diverse geographical regions regarding the probable timing of perinatal HIV transmission. On the basis of the timing of the first infant positive polymerase chain reaction or culture, most transmission would appear to occur around the intrapartum or very late prenatal period, and only approximately 12-14% is related to breast feeding. These advances should help focus and refine future research efforts to reduce mother-to-child HIV transmission worldwide. RP Fowler, MG (reprint author), NIAID,EFFICACY TRIALS BRANCH,DIV AIDS,NIH,ROOM 2A09,SOLAR BLDG,6003 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 33 TC 19 Z9 19 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD DEC PY 1997 VL 9 IS 6 BP 343 EP 348 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YK137 UT WOS:A1997YK13700001 PM 9425574 ER PT J AU Liang, LF Soyal, SM Dean, J AF Liang, LF Soyal, SM Dean, J TI FIG alpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes SO DEVELOPMENT LA English DT Article DE FIG alpha; basic helix-loop-helix transcription factor; zona pellucida; oocyte-specific gene expression; mouse ID HELIX-LOOP-HELIX; OOCYTE-SPECIFIC EXPRESSION; SPERM RECEPTOR; MOUSE OOCYTES; DNA-BINDING; DEVELOPMENTAL REGULATION; SEX DETERMINATION; INSULIN GENE; DROSOPHILA; PROTEINS AB The mouse zona pellucida is composed of three glycoproteins, ZP1, ZP2 and ZP3, encoded by single-copy genes whose expression is temporally and spatially restricted to oocytes. All three proteins are required for the formation of the extracellular zona matrix and female mice with a single disrupted zona gene lack a zona and are infertile. An E-box (CANNTG), located approximately 200 bp upstream of the transcription start sites of Zp1, Zp2 and Zp3, forms a protein-DNA complex present in oocytes and, to a much lesser extent, in testes. It has been previously shown that the integrity of this E-box in Zp2 and Zp3 promoters is required for expression of luciferase reporter genes microinjected into growing oocytes, The presence of the ubiquitous transcription factor E12 in the complex was used to identify a novel basic helix-loop-helix protein, FIG alpha (Factor In the Germline alpha) whose expression was limited to oocytes within the ovary. The ability of FIG alpha to transactivate reporter genes coupled to each of the three mouse zona promoters in heterologous 10T1/2 embryonic fibroblasts suggests a role in coordinating the expression of the three zona pellucida genes during oogenesis. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 51 TC 176 Z9 189 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1997 VL 124 IS 24 BP 4939 EP 4947 PG 9 WC Developmental Biology SC Developmental Biology GA YP435 UT WOS:000071276500003 PM 9362457 ER PT J AU Ishizuya-Oka, A Ueda, S Damjanovski, S Li, Q Liang, VCT Shi, YB AF Ishizuya-Oka, A Ueda, S Damjanovski, S Li, Q Liang, VCT Shi, YB TI Anteroposterior gradient of epithelial transformation during amphibian intestinal remodeling: Immunohistochemical detection of intestinal fatty acid-binding protein SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; THYROID-HORMONE; XENOPUS-LAEVIS; TRANSGENIC MICE; CONNECTIVE-TISSUE; DIGESTIVE-TRACT; GENE-EXPRESSION; METAMORPHOSIS; DIFFERENTIATION; PATTERNS AB To determine whether the remodeling of the well-organized intestinal epithelium during amphibian metamorphosis is regionally regulated along the anteroposterior axis of the intestine, we raised a polyclonal antibody against the Xenopus laevis intestinal fatty acid-binding protein (IFABP), which is known to be specifically expressed in intestinal absorptive cells, and examined immunohistochemically the differentiation, proliferation, and apoptosis of the epithelial cells throughout X. laevis small intestine. During pre- and prometamorphosis, IFABP-immunoreactive (ir) epithelial cells were localized only in the anterior half of the larval intestine. At the beginning of metamorphic climax, apoptotic cells detected by nick end-labeling (TUNEL) suddenly increased in number in the entire larval epithelium, concurrently with the appearance of adult epithelial primordia. Subsequently, the adult primordia in the anterior part of the intestine developed more rapidly by active cell proliferation than those in the posterior part, and replaced the larval epithelial cells earlier than those in the posterior part. IFABP-ir cells in the adult epithelium were first detectable at the tips of newly formed folds in the proximal part of the intestine. Thereafter, IFABP expression gradually progressed both in the anteroposterior direction and in the crest-trough direction of the folds. These results suggest that developmental processes of the adult epithelium in the X. laevis intestine are regionally regulated along the anteroposterior axis of the intestine, which is maintained throughout metamorphosis, and along the trough-crest axis of the epithelial folds, which is newly established during metamorphosis. Furthermore, the regional differences in IFABP expression along the anteroposterior axis of the intestine were reproduced in organ cultures in vitro. In addition, IFABP expression was first down-regulated and then reactivated in vitro when the anterior part, but not the posterior part, of the larval intestine was treated With thyroid hormone (TH) for extended periods. Therefore, it seems that, in addition to TH, an endogenous factor(s) localized in the intestine itself with an anteroposterior gradient participates in the development of the adult epithelium during amphibian metamorphosis. (C) 1997 Academic Press. C1 Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 32102, Japan. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Ishizuya-Oka, A (reprint author), Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 32102, Japan. RI Damjanovski, Sashko/N-8728-2015 NR 42 TC 54 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 1997 VL 192 IS 1 BP 149 EP 161 DI 10.1006/dbio.1997.8749 PG 13 WC Developmental Biology SC Developmental Biology GA YN254 UT WOS:000071148500012 PM 9405104 ER PT J AU Ault, KT Xu, RH Kung, HF Jamrich, M AF Ault, KT Xu, RH Kung, HF Jamrich, M TI The homeobox gene PV.1 mediates specification of the prospective neural ectoderm in Xenopus embryos SO DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; SPEMANN ORGANIZER; VENTRAL MESODERM; INDUCTION; RECEPTOR; SIGNALS; BMP-4; EXPRESSION; LAEVIS; NOGGIN AB Bone morphogenetic protein 4 (BMP4), a member of the TGF beta superfamily, has been implicated in the dorsoventral specification of both mesoderm and ectoderm. High levels of BMP4 signaling appear to specify ventral lineages, while lower levels are causally associated with the development of dorsal lineages. We have previously identified a homeobox-containing transcription factor (PV.1) which is a likely mediator of the ventralizing effects of BMP4 in the mesoderm. Here we provide evidence that PV.1 also functions downstream of BMP4 in the patterning of ectoderm, specifying epidermal and suppressing neural gene expression. PV.1 is expressed in the prospective neuroectoderm at the time of ectodermal fate determination. BMP4 and xSmad1 (a downstream effector of BMP4) induce PV.1 in uncommitted ectoderm and the dominant negative form of the BMP4 receptor (DN-BR) blocks PV.1 expression. In animal pole explants PV.1 counteracts the neuralizing effects of chordin and the DN-BR and restores them to their original epidermal fate. To address the physiological significance of these observations we employed an animal cap transplantation system and demonstrated that overexpression of PV.1 in the prospective neuroectoderm specifically blocks neurogenesis in intact embryos. Thus, PV.1 plays an important role in the ventralization of both mesoderm and ectoderm. We have previously shown that PV.1 is also preferentially expressed in the ventral endoderm, suggesting that this transcription factor may be involved in the ventralization of all three germ layers. C1 US FDA, Dev Biol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20852 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20952 USA. SAIC, Frederick, MD 21702 USA. NCI, Lab Biochem Physiol, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Ault, KT (reprint author), US FDA, Dev Biol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20852 USA. NR 41 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 1997 VL 192 IS 1 BP 162 EP 171 DI 10.1006/dbio.1997.8737 PG 10 WC Developmental Biology SC Developmental Biology GA YN254 UT WOS:000071148500013 PM 9405105 ER PT J AU Wherrett, DK Singer, SM McDevitt, HO AF Wherrett, DK Singer, SM McDevitt, HO TI Reduction in diabetes incidence in an I-A(g7) transgenic nonobese diabetic mouse line SO DIABETES LA English DT Article ID A BETA-CHAIN; MICE; MELLITUS; PREVENTION; INSULITIS; UNIQUE; GENE AB Susceptibility to IDDM is strongly associated with major histocompatibility complex (MHC) class II genotypes. Nonobese diabetic (NOD) mice develop a similar autoimmune diabetes and have a unique MHC class II I-A allele that is required for the development of diabetes. A number of groups have shown that the introduction of resistant MHC class II alleles as transgenes into the NOD mouse protects from diabetes. mie made control transgenic NOD mice, expressing their own I-A beta(g7) molecule as a transgene. One of two lines of these mice showed a reduced incidence of diabetes, without any change in T-cell proliferative response to a number of diabetes autoantigens or any change in insulitis severity. This line developed a subtle decrease in the percentage of splenic B-cells that progressed with age. This defect was not associated with any other phenotypic abnormalities. Our findings suggest that assessment of splenic B-cell number is necessary in interpretation of the effects of MHC class II transgenes on the development of diabetes in the NOD mouse. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. HOSP SICK CHILDREN,DIV ENDOCRINOL,TORONTO,ON M5G 1X8,CANADA. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 18 TC 16 Z9 16 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1997 VL 46 IS 12 BP 1970 EP 1974 DI 10.2337/diabetes.46.12.1970 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH805 UT WOS:A1997YH80500008 PM 9392482 ER PT J AU Jaffa, AA Vio, C Velarde, V LeRoith, D Mayfield, RK AF Jaffa, AA Vio, C Velarde, V LeRoith, D Mayfield, RK TI Induction of renal kallikrein and renin gene expression by insulin and IGF-I in the diabetic rat SO DIABETES LA English DT Article; Proceedings Paper CT American-Diabetes-Association Annual Meeting and Scientific Sessions CY JUN 11-14, 1994 CL NEW ORLEANS, LA SP Amer Diabet Assoc ID GROWTH-FACTOR-I; ANGIOTENSIN SYSTEM; BINDING-PROTEINS; MESSENGER-RNA; MELLITUS; KIDNEY; PRORENIN; PLASMA; HYPERFILTRATION; GLOMERULOPATHY AB The renal kallikrein-kinin system and the renin-angiotensin system are implicated in the pathogenesis of diabetic nephropathy. We have shown that renal kallikrein and renin gene expression are altered by diabetes. To investigate the cellular mechanisms responsible for these changes, we examined the effects of acute insulin and insulin-like growth factor I (IGF-I) treatment on renal kallikrein-kinin and renin-angiotensin system components. Three weeks after induc tion of diabetes, we measured renal kallikrein and renin mRNA levels, renal kallikrein and renal renin activity, and plasma renin activity in control and diabetic rats and diabetic rats treated with insulin or IGF-I for 2 or 5 h. In diabetic rats, kallikrein and renin mRNA levels were reduced >50% compared with control rats. Renal tissue kallikrein levels and plasma renin activity were decreased, whereas renal renin content was unchanged. Insulin increased kallikrein and renin mRNA levels after 2 h. IGF-I, at a dosage that stimulated kallikrein mRNA levels in control rats, had no effect on renal kallikrein and renin content or mRNA levels in diabetic rats. However, infusion of a fivefold higher IGF-I dosage resulted in a two-to threefold increase in kallikrein and renin mRNA levels in 2 h. These data suggest that 1) diabetes suppresses kallikrein and renin gene expression, and these abnormalities are reversed by insulin or IGF-I; and 2) the diabetic state produces resistance to IGF-I induction of kallikrein and renin gene expression. These changes in regulated synthesis of kallikrein and renin in the kidney may underlie renal vascular changes that develop in diabetes. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,DEPT MED,CHARLESTON,SC. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,DEPT PHARMACOL,CHARLESTON,SC. CATHOLIC UNIV,DEPT PHYSIOL,SANTIAGO,CHILE. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. OI Vio, Carlos/0000-0003-1850-5958 FU NIDDK NIH HHS [DK-46543] NR 32 TC 18 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1997 VL 46 IS 12 BP 2049 EP 2056 DI 10.2337/diabetes.46.12.2049 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH805 UT WOS:A1997YH80500021 PM 9392495 ER PT J AU Harris, MI Eastman, RC Cowie, CC Flegal, KM Eberhardt, MS AF Harris, MI Eastman, RC Cowie, CC Flegal, KM Eberhardt, MS TI Comparison of diabetes diagnostic categories in the US population according to 1997 American Diabetes Association and 1980-1985 World Health Organization diagnostic criteria SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INSULIN; MELLITUS AB OBJECTIVE - To compare the 1997 American Diabetes Association (ADA) and the 1980-1985 World Health Organization (WHO) diagnostic criteria in categorization of the diabetes diagnostic status of adults in the U.S. RESEARCH DESIGN AND METHODS - Analyses are based on a probability sample of the U.S. population age 40-74 years in the 1988-1994 Third National Health and Nutrition Examination Sun ey (NHANES III). People with diabetes diagnosed before the survey were identified by questionnaire. For 2,844 people without diagnosed diabetes, fasting plasma glucose was obtained after an overnight 9 to <24-h fast, HbA(1c) was measured, and a 2-h oral glucose tolerance test was administered. RESULTS - Prevalence of diagnosed diabetes in this age-group is 7.9%. Prevalence of undiagnosed diabetes is 4.4% by ADA criteria and 6.4% by WHO criteria. The net change of -2.0% occurs because 1.0% are classified as having undiagnosed diabetes by ADA criteria but have impaired or normal glucose tolerance by WHO criteria, and 3.0% are classified as having impaired lasting glucose or normal fasting glucose by ADA criteria but have undiagnosed diabe res by WHO criteria. Prevalence of impaired fasting glucose is 10.1% (ADA), compared with 15.6% for impaired glucose tolerance (WHO). For those with undiagnosed diabetes by ADA criteria, 62.1% are above the normal range for HbA(1c) compared with 47.1% by WHO criteria. Mean HbA(1c) is 7.07% for undiagnosed diabetes by ADA criteria and 6.58% by WHO criteria. CONCLUSIONS - The number of people with undiagnosed diabetes by ADX criteria is lower than that by WHO criteria. However, those individuals classified by ADA criteria are more hyperglycemic, with higher HbA(1c) values and a greater proportion of values above the normal range. This fact, together with the simplicity of obtaining a fasting plasma glucose value, may result in the detection of a greater proportion of people with undiagnosed diabetes in clinical practice using the new ADA diagnostic criteria. C1 NIDDKD,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 18 TC 225 Z9 229 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 1997 VL 20 IS 12 BP 1859 EP 1862 DI 10.2337/diacare.20.12.1859 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH359 UT WOS:A1997YH35900011 PM 9405907 ER PT J AU Sato, S McCutchen, C Graham, B Freeman, A von Albertini-Carletti, I Alling, DW AF Sato, S McCutchen, C Graham, B Freeman, A von Albertini-Carletti, I Alling, DW TI Relationship between muscle tone changes, sawtooth waves and rapid eye movements during sleep SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE sawtooth wave; REM; muscle tone reduction AB 'Sawtoothed' waves occur during rapid eye movement (REM) sleep, but their source as well as their function is not known. We studied the onset of sawtooth waves (STW) in relation to the onset of muscle tone reduction (MTR) and to REM during 20 polysomnographic recordings in 11 normal volunteers. Seventy-seven (85%) of a total of 91 REM sleep cycles were used for further analysis, because within a 1000 s interval they showed a relatively stereotyped sequence of events: a generalized body movement, followed by MTR, then the appearance of STW, and ending with the first REM. The first STW often occurred during the electrographic stage II period prior to the beginning of the REM, by which time muscle tone was either already at or close to the tone level of the REM sleep period in all subjects. The overall mean onset time of MTR was 267 s (range 89-660 s), STW was 378 s (range 169-779), and REM was 448 s (range 265-849); their differences were highly significant (F = 27.1, df 2,20, P < 0.001). Our data suggest that a predictable sequence of muscle tone reduction, then STW, and then REM, precedes the generally accepted onset of the REM sleep period, and may have implications for the redesignation of physiologic REM sleep onset. (C) 1997 Elsevier Science Ireland Ltd. C1 NINDS, EEG Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Off Director, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NINDS, EEG Sect, Bethesda, MD 20892 USA. EM sato@helix.nih.gov NR 11 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1997 VL 103 IS 6 BP 627 EP 632 DI 10.1016/S0013-4694(97)00072-2 PG 6 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA YU332 UT WOS:000071706700006 PM 9546490 ER PT J AU Chen, R Gerloff, C Classen, J Wassermann, EM Hallett, M Cohen, LG AF Chen, R Gerloff, C Classen, J Wassermann, EM Hallett, M Cohen, LG TI Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; safety; seizure ID PREFRONTAL CORTEX; MOTOR CORTEX; HIPPOCAMPUS; DEPRESSION; GENERATION; INDUCTION; MOOD AB Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was Likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided. Published by Elsevier Science Ireland Ltd. C1 NINCDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINCDS, Human Cort Physiol Unit, NIH, Bldg 10,Room SN226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 26 TC 133 Z9 139 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1997 VL 105 IS 6 BP 415 EP 421 DI 10.1016/S0924-980X(97)00036-2 PG 7 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YP987 UT WOS:000071336000001 PM 9448642 ER PT J AU Ziemann, U Tergau, F Bruns, D Baudewig, J Paulus, W AF Ziemann, U Tergau, F Bruns, D Baudewig, J Paulus, W TI Changes in human motor cortex excitability induced by dopaminergic and anti-dopaminergic drugs SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE paired transcranial magnetic stimulation; motor cortex; intracortical inhibition and facilitation; dopamine receptor agonists; neuroleptics ID TRANSCRANIAL MAGNETIC STIMULATION; PARKINSONS-DISEASE; BASAL GANGLIA; CORTICOCORTICAL INHIBITION; CORTICAL EXCITABILITY; MOVEMENT-DISORDERS; GENERALIZED EPILEPSY; GLOBUS-PALLIDUS; CEREBRAL-CORTEX; NEURONS AB Transcranial magnetic stimulation was used to probe the acute effect of a single oral dose of various dopaminergic (levodopa, selegiline, bromocriptine) and antidopaminergic drugs (sulpiride, haloperidol) on motor cortex excitability in healthy volunteers. Motor threshold, intracortical inhibition and intracortical facilitation were tested in the abductor digiti minimi muscle. The latter two parameters were studied in a conditioning-test paired stimulus paradigm. The principal findings were an increase in intracortical inhibition by bromocriptine, and, conversely, a decrease in intracortical inhibition and an increase in intracortical facilitation by haloperidol. Effects peaked at delays consistent with the pharmacokinetics of the two drugs and were fully reversible. In conclusion, dopamine receptor agonists and antagonists can be considered inverse modulators of motor cortex excitability: the former enhance inhibition while the latter reduce it. The relation of the present findings to current models of motor excitability abnormalities in movement disorders will be discussed. (C) 1997 Elsevier Science Ireland Ltd. C1 Univ Gottingen, Dept Clin Neurophysiol, D-37075 Gottingen, Germany. RP Ziemann, U (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N242,10 Ctr Dr, Bethesda, MD 20982 USA. RI Baudewig, Juergen/F-4468-2010; Paulus, Walter/A-3544-2009 OI Paulus, Walter/0000-0001-5549-8377 NR 56 TC 170 Z9 172 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1997 VL 105 IS 6 BP 430 EP 437 DI 10.1016/S0924-980X(97)00050-7 PG 8 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YP987 UT WOS:000071336000003 PM 9448644 ER PT J AU Floeter, MK Kohn, AF AF Floeter, MK Kohn, AF TI H-reflexes of different sizes exhibit differential sensitivity to low frequency depression SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE postactivation depression; presynaptic inhibition; human ID POST-ACTIVATION DEPRESSION; GROUP-IA SYNAPSES; CAT; MOTONEURONS; FLUCTUATIONS; POTENTIALS; PATHWAY AB The amplitude of the H-reflex declines when activated repetitively. The magnitude of decline is greater when the amplitude of the H-reflex is small. To explore whether pre-or postsynaptic factors contribute to the differences observed in H-reflexes of different sizes, changes in the amplitude of H-reflexes of different sizes were measured during a train of stimulation in IO normal subjects. Amplitudes of different sizes were obtained using differing stimulus intensities or during superimposed contraction, two manipulations which differently affect the number of active afferents and the excitation of the motoneuron pool. Small amplitude H-reflexes depressed to a lower plateau than larger H-reflexes and superimposed contraction did not alleviate the depression during each train. Nearly all the decline in larger amplitude H-reflexes occurred in a component that was in common with smaller amplitude H-reflexes. This suggests that the depressibility of the earliest activated units is greater than later activated units in H-reflexes and that the magnitude of decline is affected by prior activity as well as size. (C) 1997 Elsevier Science ireland Ltd. C1 NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. RP NINDS, EMG Sect, NIH, 10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA. RI Kohn, Andre/N-4982-2016 OI Kohn, Andre/0000-0002-9770-3348 NR 25 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1997 VL 105 IS 6 BP 470 EP 475 PG 6 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YP987 UT WOS:000071336000008 PM 9448649 ER PT J AU Lemkin, PF AF Lemkin, PF TI The 2DWG meta-database of two-dimensional electrophoretic gel images on the Internet SO ELECTROPHORESIS LA English DT Article DE World Wide Web; Internet; two-dimensional polyacrylamide gel electrophoresis; databases; meta-database; proteins; genetics; image analysis ID LIVER PROTEIN MAP; SWISS-2DPAGE DATABASE; UPDATE 1993; PLASMA AB The 2DWG meta-database is a searchable database of two-dimensional (2-D) electrophoretic gel images found on the Internet. A meta-database contains information about locating data in other databases - but not that data itself. This database was constructed because of a need for an enriched set of World Wide Web (WWW) locations (URLs) of 2-D gel images on the Internet. These gel images are used in conjunction with the National Cancer Institute (NCI) Flicker Server to manipulate and visually compare 2-D gel images across the Internet. User's gels may also be compared with those in the database. The 2DWG is organized as a spreadsheet table with each gel image being represented by a row sorted by tissue type. Data for each gel includes tissue type, species, cell-line, image URL, database URL, gel protocol, organization URL, image properties, map URL if it exists, etc. The 2DWG may be searched to find relevant subsets of gels. Searching is done using the dbEngine - a WWW database search engine which accesses selected rows of gels from the full 2DWG table. The 2DWG meta-database is accessible on the WWW at http://www-lecb.ncifcrf.gov/2dwgDB/ and the NCI Flicker server at http://wwwlecb.ncifcrf.gov/flicker/. C1 NCI, Frederick Canc Res & Dev Ctr, Image Proc Sect, LECB,NIH, Frederick, MD 21702 USA. RP Lemkin, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Image Proc Sect, LECB,NIH, Bld 469 Room 150, Frederick, MD 21702 USA. EM lemkin@ncifcrf.gov NR 35 TC 26 Z9 26 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1997 VL 18 IS 15 BP 2759 EP 2773 DI 10.1002/elps.1150181510 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YW557 UT WOS:000071948300009 PM 9504808 ER PT J AU Greenberg, ME Bronson, S Lock, M Neumann, M Pavlakis, GN Skowronski, J AF Greenberg, ME Bronson, S Lock, M Neumann, M Pavlakis, GN Skowronski, J TI Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation SO EMBO JOURNAL LA English DT Article DE adaptor complex; CD4; endocytosis; HIV; Nef ID IMMUNODEFICIENCY-VIRUS TYPE-1; GREEN-FLUORESCENT PROTEIN; LONG-TERM SURVIVOR; CELL-SURFACE CD4; T-CELLS; CYTOPLASMIC DOMAIN; BINDING SURFACE; SH3 DOMAIN; EXPRESSION; ACTIVATION AB The nef gene of human and simian immunodeficiency viruses is critical for AIDS pathogenesis. Its function in vivo is unknown, but in vitro natural isolates of Nef down-regulate expression of the cell surface CD4 molecule, a component of the T cell antigen receptor and the viral receptor, by accelerating its endocytosis, We have used chimeric proteins comprised of the natural HIV-1 NA7 Nef fused to a strongly fluorescing mutant of green fluorescent protein (GFP) to correlate Nef function with intracellular localization in human CD4-positive Jurkat T cells, The NA7-GFP fusion protein co-localizes with components of the clathrin coat, including clathrin and the beta-subunit of the AP-2 adaptor protein complex, at discrete locations that are consistent with the normal cellular distribution of clathrin coats at the plasma membrane, The NA7-GFP protein is also found in the perinuclear region of the cell, which is likely to reflect the Golgi apparatus, Evidence from a CD4-negative fibroblast cell line indicates that co-localization of NA7-GFP with components of the clathrin coat does not require expression of the CD4 molecule, Analysis of a large panel of chimeric molecules containing mutant Nef moieties demonstrated that the N-terminal membrane targeting signal cooperates with additional element(s) in the disordered loops in the Nef molecule to co-localize the Nef protein with AP-2 adaptor complexes at the cell margin. This localization of NA7-GFP correlates with, but is not sufficient for, down-regulation of surface CD4 and at least one additional function of Nef is required, In T cells co-expressing CD4 and NA7-GFP, CD4 at the cell surface is redistributed into a discrete pattern that co-localizes with that of NA7-GFP, Our observations place NA7-GFP in physical proximity to AP-2-containing clathrin coat at the plasma membrane and imply that Nef interacts, either directly or indirectly, with a component of the AP-2-containing coat at this location, This evidence supports a model whereby Nef recruits CD4 to the endocytic machinery via AP-2-containing clathrin coats at the plasma membrane. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Skowronski, J (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. FU PHS HHS [IA-35394] NR 51 TC 182 Z9 183 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1997 VL 16 IS 23 BP 6964 EP 6976 DI 10.1093/emboj/16.23.6964 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YM353 UT WOS:000071055100008 PM 9384576 ER PT J AU Wong, JM Li, Q Levi, BZ Shi, YB Wolffe, AP AF Wong, JM Li, Q Levi, BZ Shi, YB Wolffe, AP TI Structural and functional features of a specific nucleosome containing a recognition element for the thyroid hormone receptor SO EMBO JOURNAL LA English DT Article DE chromatin structure; linker histones; nuclear receptors; nucleosome positioning; transcriptional regulation ID RIBOSOMAL-RNA GENE; GLUCOCORTICOID RESPONSE ELEMENT; TRANSCRIPTION FACTOR ACCESS; TUMOR VIRUS PROMOTER; LINKER HISTONES; POSITIONED NUCLEOSOMES; GLOBULAR DOMAIN; CORE HISTONES; BINDING-SITE; IN-VIVO AB The Xenopus thyroid hormone receptor beta A (TR beta A) gene contains an important thyroid hormone response element (TRE) that is assembled into a positioned nucleosome. We determine the translational position of the nucleosome containing the TRE and the rotational positioning of the double helix with respect to the histone surface. Histone H1 is incorporated into the nucleosome leading to an asymmetric protection to micrococcal nuclease cleavage of linker DNA relative to the nucleosome core. Histone H1 association is without significant consequence for the binding of the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR/RXR) to nucleosomal DNA in vitro, or for the regulation of TR beta A gene transcription following microinjection into the oocyte nucleus. Small alterations of 3 and 6 bp in the translational positioning of the TRE in chromatin are also without effect on the transcriptional activity of the TR beta A gene, whereas a small change in the rotational position of the TRE (3 bp) relative to the histone surface significantly reduces the binding of TR/RXR to the nucleosome and decreases transcriptional activation directed by TR/RXR. Our results indicate that the specific architecture of the nucleosome containing the TRE may have regulatory significance for expression of the TR beta A gene. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 80 TC 69 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1997 VL 16 IS 23 BP 7130 EP 7145 DI 10.1093/emboj/16.23.7130 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YM353 UT WOS:000071055100022 PM 9384590 ER PT J AU Bocchinfuso, WP Korach, KS AF Bocchinfuso, WP Korach, KS TI Biological impact of a disrupted estrogen receptor gene on estrogen-related cancer SO ENDOCRINE-RELATED CANCER LA English DT Review ID MOUSE MAMMARY-GLAND; EPIDERMAL GROWTH-FACTOR; LIGAND-BINDING DOMAIN; HUMAN BREAST-CANCER; TRANSGENIC MICE; TYROSINE KINASE; CYCLIN D1; TRANSCRIPTIONAL ACTIVATION; DUCTAL MORPHOGENESIS; TARGETED DISRUPTION C1 NIEHS, RECEPTOR BIOL SECT, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 126 TC 2 Z9 2 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD WIN PY 1997 VL 4 IS 4 BP 387 EP 406 PG 20 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA YJ857 UT WOS:A1997YJ85700001 ER PT J AU RabadanDiehl, C Makara, G Kiss, A Lolait, S Zelena, D Ochedalski, T Aguilera, G AF RabadanDiehl, C Makara, G Kiss, A Lolait, S Zelena, D Ochedalski, T Aguilera, G TI Regulation of pituitary V1b vasopressin receptor messenger ribonucleic acid by adrenalectomy and glucocorticoid administration SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; MEDIAN-EMINENCE; STIMULATED ADRENOCORTICOTROPIN; ARGININE-VASOPRESSIN; PARAVENTRICULAR NUCLEUS; CHRONIC STRESS; PORTAL PLASMA; SECRETION; RAT; OXYTOCIN AB Regulation of the number of pituitary vasopressin (VP) receptors plays an important role in controlling pituitary responsiveness during alterations of the hypothalamic pituitary adrenal axis. The mechanisms regulating these VP receptors were studied by analysis of the effects of adrenalectomy and glucocorticoid administration on V1b receptor (V1b-R) messenger RNA (mRNA) by Northern blot and by in situ hybridization in the rat. Adrenalectomy transiently decreased V1b-R mRNA levels by 18 h (77% and 62% for the 3.7-kb and 3.2-kb bands in the Northern blots, and 50% by in situ hybridization), returning to basal levels after 6 days. The decrease in V1b-R mRNA after 18 h adrenalectomy was fully prevented by dexamethasone (100 mu g sc) but not by elimination of hypothalamic CRH and VP by paraventricular nucleus lesions or median eminence deafferentation. In sham-operated rats, dexamethasone increased receptor mRNA by 50% after 6 days. In contrast to Sprague-Dawley rats, in Brattleboro rats (di/di), which lack hypothalamic VP, adrenalectomy caused a sustained decrease in V1b-R mRNA levels (<50% of controls by 6 days). The data show that pituitary V1b-R mRNA is positively regulated by glucocorticoids and that the recovery of V1b-R mRNA levels after prolonged adrenalectomy is probably mediated by VP. In addition, the data suggest that the down-regulation of VP binding after long-term adrenalectomy is due to posttranscriptional events rather than to changes in V1b-R mRNA. C1 NICHHD,SECT ENDOCRINE PHYSIOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,INST EXPT MED,H-1450 BUDAPEST,HUNGARY. NIMH,LAB MOL & CELLULAR REGULAT,NIH,BETHESDA,MD 20892. RI Makara, Gabor/H-8397-2013 OI Makara, Gabor/0000-0001-9220-0373 NR 41 TC 32 Z9 32 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 DEC PY 1997 VL 138 IS 12 BP 5189 EP 5194 DI 10.1210/en.138.12.5189 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH190 UT WOS:A1997YH19000016 PM 9389500 ER PT J AU Lin, KH Zhu, XG Hsu, HC Chen, SL Shieh, HY Chen, ST McPhie, P Cheng, SY AF Lin, KH Zhu, XG Hsu, HC Chen, SL Shieh, HY Chen, ST McPhie, P Cheng, SY TI Dominant negative activity of mutant thyroid hormone alpha 1 receptors from patients with hepatocellular carcinoma SO ENDOCRINOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; NUCLEAR RECEPTORS; RESPONSE ELEMENT; CO-REPRESSOR; RESISTANCE; DNA; BETA; IDENTIFICATION; DETERMINANTS; MODULATION AB Complementary DNAs for two mutant thyroid hormone (yl receptors (TR alpha 1) were isolated from hepatocellular carcinomas of two patients. Sequence analyses of the complementary DNAs showed a single Val(390)Ala and double Pro(398)Ser/Glu(350)Lys mutations in mutants H and L, respectively. We characterized their hormone-binding, DNA-binding, and dominant negative activities. Mutants H and L did not bind the hormone T-3,. Their DNA-binding activities were analyzed using three types of thyroid hormone response elements (TREs) in which the half-site binding motifs are arranged in an everted repeat (Lys), an inverted repeat (Pal), or a direct repeat separated by four nucleotides (DR4). Compared with wild-type TR alpha 1 (w-TR alpha 1), which bound these TREs with different homodimer/monomer ratios, binding of mutant L to the three TREs as homodimers was reduced by similar to 90%. However, binding of mutant H to these TREs was more complex. Although it bound normally to DR4 as homodimers, its binding to Lys as homodimers was reduced by similar to 80%. Surprisingly, its binding to Pal was markedly enhanced compared with w-TR alpha 1. The binding of these two mutants to the three TREs as heterodimers with retinoid X receptors (RXR alpha and -beta) was not significantly affected. Consistent with the lack of T-3-binding activity, both mutants had lost their trans-activation capacity. Mutants H and L exhibited dominant negative activity, but differed in their TRE dependency. The dominant negative potency of mutant H was in the rank order of Pal > DR4 > Lys, whereas no TRE dependency was observed for mutant L. The present study indicates that mutations of the TR alpha gene do occur in patients and that these novel TR alpha 1 mutants provide a valuable tool to further understand the molecular basis of the dominant negative action of mutant TRs. C1 NCI,MOL BIOL LAB,CTR GENE REGULAT,BETHESDA,MD 20892. BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NIDDK,BETHESDA,MD 20892. RP Lin, KH (reprint author), CHANG GUNG COLL MED & TECHNOL,DEPT BIOCHEM,TAYUAN,TAIWAN. NR 38 TC 39 Z9 40 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1997 VL 138 IS 12 BP 5308 EP 5315 DI 10.1210/en.138.12.5308 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH190 UT WOS:A1997YH19000031 PM 9389515 ER PT J AU Heinrichs, C Colli, M Yanovski, JA Laue, L Gerstl, NA Kramer, AD Uyeda, JA Baron, J AF Heinrichs, C Colli, M Yanovski, JA Laue, L Gerstl, NA Kramer, AD Uyeda, JA Baron, J TI Effects of fasting on the growth plate: Systemic and local mechanisms SO ENDOCRINOLOGY LA English DT Article ID HORMONE-BINDING-PROTEIN; MESSENGER-RIBONUCLEIC-ACID; LONGITUDINAL BONE-GROWTH; FACTOR-I GENE; IGF-I; NUTRITIONAL REGULATION; REFED RATS; RNA LEVELS; INSULIN; RECEPTOR AB Inadequate caloric intake inhibits longitudinal bone growth. This study was designed to investigate the mechanisms responsible for this suppression of growth plate function, focusing on the roles of systemic and local insulin-like growth factor 1 (IGF-1). Five week-old male rabbits were fasted for 48 h. Fasting significantly decreased proximal tibial growth velocity and growth plate width (both proliferative and hypertrophic zones). During the fast, systemic IGF-1 production was down-regulated. Serum IGF-1 levels and hepatic IGF-1 messenger RNA (mRNA) levels decreased despite increased GH levels. Serum levels of GH binding protein (a circulating fragment of the GH receptor) and hepatic GH receptor mRNA levels were not significantly changed. In contrast, the local, growth plate IGF-1 system appeared to be up-regulated. Growth plate GH receptor mRNA and IGF-1 mRNA levels were both increased during fasting. We conclude that, in the rabbit, fasting induces a rapid depletion of growth plate chondrocytes and inhibition of longitudinal bone growth. These effects appear to be mediated by systemic endocrine mechanisms; circulating IGF-1 levels are diminished because of hepatic resistance to GH. In contrast, the local, paracrine IGF-1 system in growth plate does not appear to contribute to the growth inhibition but instead appears to be up-regulated by fasting. C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 39 TC 41 Z9 41 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1997 VL 138 IS 12 BP 5359 EP 5365 DI 10.1210/en.138.12.5359 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH190 UT WOS:A1997YH19000037 PM 9389521 ER PT J AU Tarasova, N Spannagel, AW Green, GM Gomez, G Reed, JT Thompson, JC Hellmich, MR Reeve, JR Liddle, RA Greeley, GH AF Tarasova, N Spannagel, AW Green, GM Gomez, G Reed, JT Thompson, JC Hellmich, MR Reeve, JR Liddle, RA Greeley, GH TI Distribution and localization of a novel cholecystokinin-releasing factor in the rat gastrointestinal tract SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC-ENZYME SECRETION; TRYPSIN-INHIBITOR; FEEDBACK-REGULATION; PEPTIDE; PLASMA; RADIOIMMUNOASSAY; PURIFICATION; SUPPRESSION; JUICE; GUT AB The purpose of this study was to examine the distribution and localization of an intestinal cholecystokinin (CCK)-releasing factor, called luminal CCK-releasing factor (LCRF), in the gastrointestinal tract and pancreas of the rat. RIA analysis indicates that LCRF immunoreactivity is found throughout the gut including the pancreas, stomach, duodenum, jejunum, ileum, and colon with the highest levels in the small intestine. Immunohistochemistry analysis shows LCRF immunoreactivity Staining in intestinal villi, Brunner's glands of the duodenum, the duodenal myenteric plexus, gastric pits, pancreatic ductules, and pancreatic islets. These results indicate potential sources for secretagogue-stimulated release of luminal LCRF and support the hypothesis that LCRF is secreted into the intestinal lumen to stimulate CCK release from mucosal CCK cells. C1 UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. VET ADM W LOS ANGELES,CTR ULCER RES & EDUC,LOS ANGELES,CA 90073. VET ADM W LOS ANGELES,DIGEST DIS RES CTR,LOS ANGELES,CA 90073. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. FU NIDDK NIH HHS [DK-37482, DK-37842, DK-15241] NR 23 TC 17 Z9 17 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1997 VL 138 IS 12 BP 5550 EP 5554 DI 10.1210/en.138.12.5550 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH190 UT WOS:A1997YH19000060 PM 9389543 ER PT J AU Martinez, A Elsasser, TH MuroCacho, C Moody, TW Miller, MJ Macri, CJ Cuttitta, F AF Martinez, A Elsasser, TH MuroCacho, C Moody, TW Miller, MJ Macri, CJ Cuttitta, F TI Expression of adrenomedullin and its receptor in normal and malignant human skin: A potential pluripotent role in the integument SO ENDOCRINOLOGY LA English DT Article ID PEPTIDE; CELLS AB Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including growth regulation and antimicrobial activity. We have determined by immunohistochemistry and in situ. hybridization that AM and its receptor are present in all the epithelial cells of the normal skin, including keratinocytes of the epidermis and hair follicles, as well as cells of the glands and secretory ducts. We also have detected AM in the sweat, by RIA. In addition, AM and its receptor were found in skin tumors of different histologies. The presence of AM and its receptor in normal and neoplastic skin was confirmed by RT-PCR and Western blot analysis performed on cell extracts from human skin cell lines. Radiolabeled AM bound to specific sites in cultured cells with a K-d of 9 nM. This binding was blocked by the addition of cold AM but not by related peptides such as AM 22-52, pro-AM 20 N-terminal peptide, calcitonin gene-related peptide, calcitonin gene-related peptide 8-37, or amylin. Finally, exposure to synthetic AM resulted in an increase of thymidine intake by skin cells. These results implicate AM as a potential player in skin defense against infectious microorganisms and as a possible autocrine growth factor in normal skin physiology and tumor development. C1 USDA ARS,BELTSVILLE,MD 20705. H LEE MOFFITT CANC CTR,DEPT PATHOL,TAMPA,FL 33612. UNIFORMED SERV UNIV HLTH SCI,DEPT OBSTET & GYNECOL,BETHESDA,MD 20814. RP Martinez, A (reprint author), NCI,CELL & CANC BIOL DEPT,DIV CLIN SCI,MED BRANCH,NIH,9610 MED CTR DR,ROOM 300,ROCKVILLE,MD 20850, USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 25 TC 88 Z9 91 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1997 VL 138 IS 12 BP 5597 EP 5604 DI 10.1210/en.138.12.5597 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YH190 UT WOS:A1997YH19000065 PM 9389548 ER PT J AU Doppman, JL AF Doppman, JL TI Problems in endocrinologic imaging SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID PERSISTENT PRIMARY HYPERPARATHYROIDISM; PARATHYROID ADENOMA; CUSHINGS-SYNDROME; CHEMICAL-SHIFT; ADRENAL MASSES; MANAGEMENT; CT; HYPERALDOSTERONISM; LOCALIZATION; DISTINCTION AB Imaging, particularly cross-sectional computer-assisted techniques such as CT and MR imaging, has become so refined and even breathtaking that the display of anatomy is beguiling endocrinologists into an unhealthy reliance on visual data. The demonstration of a focal abnormality in an endocrine gland tells us nothing about its function. Overreliance on such displays of anatomy leads to problems in diagnosis and treatment. This article points out some instances in which imaging is deceptive. RP Doppman, JL (reprint author), NIH,DEPT DIAGNOST RADIOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 1C660,10 CTR DR MSC 1182,BETHESDA,MD 20892, USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 1997 VL 26 IS 4 BP 973 EP & DI 10.1016/S0889-8529(05)70290-5 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YK828 UT WOS:A1997YK82800015 PM 9429868 ER PT J AU Levin, ED Schmechel, DE Burkholder, JM Glasgow, HB Deamer-Melia, NJ Moser, VC Harry, GJ AF Levin, ED Schmechel, DE Burkholder, JM Glasgow, HB Deamer-Melia, NJ Moser, VC Harry, GJ TI Persisting learning deficits in rats after exposure to Pfiesteria piscicida SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 1997 CL CINCINNATI, OHIO SP Soc Toxicol DE dinoflagellates; learning; memory; persisting; Pfiesteria; radial-arm maze; toxic ID RADIAL-ARM MAZE; FUNCTIONAL OBSERVATIONAL BATTERY; TOXIC ESTUARINE DINOFLAGELLATE; REPEATED ACQUISITION AB Pfiesteria piscicida and other toxic Pfiesteria-like dinoflagellates have been implicated as a cause of fish kill in North Carolina estuaries and elsewhere. Accidental exposure of humans to P. piscicida has been reported to cause a complex syndrome including cognitive impairment. The current project was conducted to experimental assess the possibility of cognitive effects of P. piscicida exposure in rats. Samples of water from Aquaria in which P. piscicida zoospores were killing fish frozen, a procedure that has been found to induce encystment. Thawed samples were injected into albino Sprague-Dawley rats. A significant learning impairment was documented in rats administered samples P. piscicida that were recently frozen. Prolonged storage of Pfiesteria samples diminished the effect. No effect was seen in the recall of a previously learned task, but when the rats were called upon to learn a new task, the Pfiesteria-treated animals showed a significant learning deficit. This effect persisted up to at least 10 weeks after a single injection of Pfiesteria. The Pfiesteria-induced learning deficit did not seem associated with any obvious debilitation or health impairment of the exposed rats. Deficits in habitation of arousal and rearing behavior were detected using a functional observational battery. No Pfiesteria-induced effects on blood count and white cell differential or in a standard pathological screening of brain, liver, lung, kidney, and spleen tissue were seen at 2 months after exposure. These studies document a persistent learning impairment in rats after exposure to the dinoflagellate P. piscicida in otherwise physically well-appearing rats. This effect may partially model the symptoms of cognitive impairments that humans have shown after Pfiesteria exposure. C1 Duke Univ, Med Ctr, Dept Psychiat, Neurobehav Res Lab, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Neurobiol & Med, Durham, NC 27710 USA. Vet Adm Med Ctr, Durham, NC 27705 USA. N Carolina State Univ, Dept Bot, Raleigh, NC 27695 USA. US EPA, Div Neurotoxicol, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Levin, ED (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Neurobehav Res Lab, 341 Bell Bldg,Box 3412, Durham, NC 27710 USA. NR 19 TC 42 Z9 42 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1997 VL 105 IS 12 BP 1320 EP 1325 DI 10.1289/ehp.971051320 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZE681 UT WOS:000072819500015 PM 9405328 ER PT J AU Gulson, BL Mahaffey, KR Jameson, CW Vidal, M Law, AJ Mizon, KJ Smith, AJM Korsch, MJ AF Gulson, BL Mahaffey, KR Jameson, CW Vidal, M Law, AJ Mizon, KJ Smith, AJM Korsch, MJ TI Dietary lead intakes for mother/child pairs and relevance to pharmacokinetic models SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE child; diet; lead isotopes; models; mother ID BLOOD LEAD; PRESCHOOL-CHILDREN; NUTRITIONAL FACTORS; NATIONAL-HEALTH; HUMAN SKELETON; UNITED-STATES; METABOLISM; ABSORPTION; BONE; FOOD AB Blood and environmental samples, including a quarterly G-day duplicate diet, for nine mother/child pairs from Eastern Europe have been monitored for 12 to > 24 months with high precision stable lead isotope analysis to evaluate the changes that occur when the subjects moved from one environment. (Eastern Europe) to another with different stable lead isotopes (Australia). The children were between 6 and 11 years of age and the mothers were between 29 and 37 pars of age. These data were compared with an Australian control mother/child pair, aged 31 and 6 years, respectively. A rationale for undertaking this study of mother/child pairs was to evaluate if there were differences in the patterns and clearance rates of lead from blood in children compared with their mothers. Blood lead concentrations ranged from 2.1 to 3.9 mu g/dl in the children and between 1.8 and 4.5 mu g/dl in the mothers, but the mean of differences between each mother and her child did not differ significantly from zero, Duplicate diets contained from 2.4 to 31.8 mu g Pb/kg diet; the mean +/- standard deviation was 5.5 +/- 2.1 mu g Pb/kg and total daily dietary intakes ranged from 1.6 to 21.3 mu g/day. Mean daily dietary intakes relative to body weight showed that the intake fur children was approximately double that for the mothers (0.218 vs, 0.113 mu g Pb/kg body weight/day), The correlations between blood lead concentration and mean daily dietary intake either relative to body weight or total dietary intake did not reach statistical significance (p>0.05), Estimation of the lead coming from skeletal (endogenous) sources relative to the contribution from environmental (exogenous) sources ranges from 8 to 70% for the mothers and 12 to 66% for the children. The difference between mothers and children is not statistically significant (p = 0.28). The children do not appear to achieve the Australian lead isotopic profile at a faster rate than their mothers, These data provide evidence that the absorption or uptake of lead from dietary sources is similar in adult females and children of the age in this study. In spire of lower bone lead and faster bone remodeling and recycling in children compared with adult females, we see no differences between the mothers and their children in overall contribution of tissue lead to blood lead, Results from this study suggest that fractional absorption of ingested lead by children 6-11 years of age is comparable with absorption patterns observed among adult females in the 29-37-year-old age range. Because pharmacokinetic models apply a 40-50% absorption even for a 7-year-old children, further investigations on fractional absorption of ingested lead Ly young children are warranted. Further investigations are especially needed in younger children than those who were subjects in the current study, particularly children in the 1-3-year-old age range. In addition, the effect of nutritional status and patterns of food intake on children's lead absorption require investigation, particularly given the increased prevalence of marginal nutritional status among low-income populations that are at increased risk of elevated elevated blood lead levels. C1 Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. CSIRO, Div Explorat & Min, N Ryde, NSW 2113, Australia. US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Macquarie Univ, CSIRO, Div Math & Informat Sci, Sydney, NSW 2109, Australia. RP Gulson, BL (reprint author), Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. FU NIEHS NIH HHS [N01-ES-05292] NR 42 TC 40 Z9 43 U1 1 U2 5 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1997 VL 105 IS 12 BP 1334 EP 1342 DI 10.2307/3433753 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZE681 UT WOS:000072819500017 PM 9405326 ER PT J AU Grassman, J AF Grassman, J TI Acquired risk factors and susceptibility to environmental toxicants SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 3rd Annual NHEERL Symposium on Susceptibility and Risk Assessment CY SEP 24-27, 1996 CL DURHAM, NORTH CAROLINA SP NHEERL DE susceptibility; risk factors; acquired factors; constitutive factors ID LIVER-CANCER RISK; REPUBLIC-OF-CHINA; BETA-CAROTENE; ASTHMA MORTALITY; CHILDHOOD ASTHMA; HEPATOCELLULAR-CARCINOMA; CARDIOVASCULAR-DISEASE; AFLATOXIN EXPOSURE; MATERNAL SMOKING; ALPHA-TOCOPHEROL AB Susceptibility to illness after exposure to environmental toxicants is determined by the interaction of numerous factors involving both constitutive and acquired traits. Constitutive susceptibility (risk) factors are the intrinsic traits determined by developmental stage, gender, and genetic makeup. Within a population, changes in constitutive risk factors tend to occur slowly, through aging, alterations in the birth or death rate, or by migration in or out of the population. Often overlooked is the effect of acquired susceptibility factors on susceptibility to environmental toxicants. Acquired susceptibility factors, which are related to the effects of living conditions, psychosocial factors, diet, behavior and access to medical care, may modify the effect of constitutive factors. Three examples demonstrate the interaction of acquired susceptibility factors with exposure and constitutive factors. The increased prevalence of asthma in children is suspected of having a strong environmental component but the underlying acquired susceptibility factors, if any, are difficult to identify because of the multifactorial nature of asthma and the use of surrogate risk factors such as parent's education. beta-Carotene is a dietary component which may modify acquired susceptibility. While numerous observational studies find that dietary beta-carotene reduces the risk of lung cancer in cigarette smokers, intervention studies do not support this role. Hepatitis B is an example of an infectious agent functioning as an acquired susceptibility factor. Hepatitis B synergistically increases the risk of hepatocellular carcinoma when accompanied by exposure to aflatoxin, a relationship that may be modified by constitutive risk factors, such as epoxide hydrolase capabilities. Acquired risk factors have the potential to greatly influence risk and their impact should be included in future studies of the health effects of environmental toxicants. (C) 1997 Elsevier Science B.V. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Grassman, J (reprint author), NIEHS, PO 12233,MC C4-05, Res Triangle Pk, NC 27709 USA. EM grass-man@niehs.nih.gov NR 53 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD DEC PY 1997 VL 4 IS 3-4 BP 209 EP 217 DI 10.1016/S1382-6689(97)10013-8 PG 9 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA YV460 UT WOS:000071826600004 PM 21781823 ER PT J AU Bennett, LM Wiseman, RW AF Bennett, LM Wiseman, RW TI Mouse models for breast cancer susceptibility SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 3rd Annual NHEERL Symposium on Susceptibility and Risk Assessment CY SEP 24-27, 1996 CL DURHAM, NORTH CAROLINA SP NHEERL DE breast cancer; gene targeting; p53; BRCA1; BRCA2; ATM ID TUMOR-SUPPRESSOR GENE; ATAXIA-TELANGIECTASIA; BRCA1 MUTATIONS; DEFICIENT MICE; P53; FAMILIES; IDENTIFICATION; TUMORIGENESIS; CARRIERS; RISKS AB Breast cancer is the most common form of malignancy in American women. Apart from age, a strong family history of breast cancer confers the highest known risk for neoplastic development by the various etiologic factors identified to date. Four genes have been identified (p53, BRCA1, BRCA5 ATM) that appear to confer substantial predispositions to human breast cancer. Gene targeting techniques have been used to create mice with specific defects in these genes. This review describes the status of these mice as models for breast cancer susceptibility and suggests future research directions which may increase our understanding of breast carcinogenesis. (C) 1997 Elsevier Science B.V. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Bennett, LM (reprint author), NIEHS, Mol Carcinogenesis Lab, Mail Drop C4-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 39 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD DEC PY 1997 VL 4 IS 3-4 BP 283 EP 288 DI 10.1016/S1382-6689(97)10024-2 PG 6 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA YV460 UT WOS:000071826600015 PM 21781834 ER PT J AU Jonsson, EG Goldman, D Spurlock, G Gustavsson, JF Nielsen, DA Linnoila, M Owen, MJ Sedvall, GC AF Jonsson, EG Goldman, D Spurlock, G Gustavsson, JF Nielsen, DA Linnoila, M Owen, MJ Sedvall, GC TI Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE tryptophan hydroxylase gene; catechol-O-methyltransferase gene; monoamine ID CEREBROSPINAL-FLUID; PREMENSTRUAL-SYNDROME; PHARMACOGENETICS; CHROMOSOME-22; FLUOXETINE; STEROIDS; RAT AB Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated possible relationships between DNA polymorphisms in the tryptophan hydroxylase (TPH) and catechol-O-methyltransferase (COMT) genes and CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = = 66). Lower CSF 5-HIAA levels were found in men with the TPH U allele (p = 0.005), but not in women. A similar but less significant pattern was observed for CSF HVA. No relationship was found between the TPH polymorphism and CSF MHPG. COMT genotypes did not relate significantly to MM concentrations. The results suggest that TPH genotypes participate differentially in the regulation of serotonin turnover rate under presumed steady state in the central nervous system of men. Due to the uncertain functional relevance of the DNA polymorphism investigated and the many calculations performed, the results should be interpreted with caution until replicated. C1 Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. NIAAA, Neurogenet Lab, Div Intramural Clin & Biol Res, Rockville, MD 20892 USA. Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. NIAAA, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. RP Jonsson, EG (reprint author), Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. RI Nielsen, David/B-4655-2009; turton, miranda/F-4682-2011; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU PHS HHS [44814] NR 35 TC 94 Z9 97 U1 0 U2 4 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD DEC PY 1997 VL 247 IS 6 BP 297 EP 302 DI 10.1007/BF02922258 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YP451 UT WOS:000071278100002 PM 9477008 ER PT J AU Repo, E Virkkunen, M Rawlings, R Linnoila, M AF Repo, E Virkkunen, M Rawlings, R Linnoila, M TI Suicidal behavior among Finnish fire setters SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE fire setting; suicide attempt; slashing ID VIOLENT OFFENDERS; FAMILY HISTORY; PERSONALITY-DISORDER; CEREBROSPINAL-FLUID; ALCOHOLISM; ARSONISTS; RISK; FIRESETTERS; RECIDIVISM; 5-HIAA AB Histories of serious suicide attempts and slashing were investigated among Finnish fire setters. Medical and criminal records of 304 fire setters were examined to compare those who had attempted suicide with those who had not, and those who had slashed themselves with those who had not using biological, diagnostic, and demographic variables. Major mood disorders, father's alcoholism, and suicidal motive of fire setting (self-immolation) were significantly associated with suicide attempts. Paternal violent alcoholism, father's criminality, and suicidal motive of fire setting were significantly associated with slashing. Among fire setters, non-lethal slashing is a predictor of serious suicidality. Associations between psychiatric diagnoses, family history, and suicidality among fire setters are similar to those reported for suicidal patients with mood and substance abuse diagnoses. Therefore, studying fire setters, who exhibit an extremely high incidence of suicidal behavior, is an effective way to elucidate psychobiology of suicidal behaviors. C1 Univ Helsinki, Cent Hosp, Dept Forens Psychiat, FIN-00180 Helsinki, Finland. NIAAA, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. RP Repo, E (reprint author), Univ Helsinki, Cent Hosp, Dept Forens Psychiat, FIN-00180 Helsinki, Finland. NR 39 TC 7 Z9 7 U1 0 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD DEC PY 1997 VL 247 IS 6 BP 303 EP 307 DI 10.1007/BF02922259 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YP451 UT WOS:000071278100003 PM 9477009 ER PT J AU Rai, SS Wolff, J AF Rai, SS Wolff, J TI Vinblastine-induced formation of tubulin polymers is electrostatically regulated and nucleated SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE vinblastine; polymerization; oligoanion; light scattering; critical concentration ID MICROTUBULE-ASSOCIATED PROTEINS; CALF BRAIN TUBULIN; BETA-TUBULIN; FLUORESCENT INDICATOR; INDUCED AGGREGATION; SELF-ASSOCIATION; VINCA ALKALOIDS; BINDING; MAGNESIUM; INVITRO AB Vinblastine promotes tubulin polymerization as measured by turbidity at 400 nm. Unlike microtubule assembly, this mode of polymerization does not require GTP and, in fact, GTP inhibits polymerization, as do other G nucleotides in the potency order: GtetraP greater than or equal to GTP > GDP > GMP > no nucleotide. Inhibition is not nucleoside-specific as ATP, ADP, and CTP also inhibit, and inorganic oligophosphates are as inhibitory as nucleotides in the order tetraphosphate approximate to triphosphate > pyrophosphate much greater than phosphate. Inhi bition of polymerization is a rough function of the number of anionic charges and can be mimicked by suramin or tartrate. It is not due to sequestration of magnesium or to debinding of vinblastine. The anion-induced decrease in turbidity generation is reflected in the amount of tubulin that is pelletable, but even in the absence of turbidity significant pelletable tubulin persists which can be assessed by 90 degrees light scattering. Formation of this polymer is less sensitive to anions. Shearing of GTP-inhibited and vinblastine-induced samples promotes turbidity and addition of seeds made from vinblastine polymers leads to rapid increases in turbidity in a concentration-dependent manner. Adjustment of the vinblastine concentration permits the demonstration of a latent period for polymerization that can be shortened by polymer seeds. Vinblastine induced polymerization shows a critical concentration, and, in the presence of GTP, two distinct critical concentrations can be identified. We conclude that charge-charge interactions play a significant role in the formation of vinblastine-induced polymers, and that their formation is a two-step process resembling a nucleation/elongation mechanism. C1 NIDDK,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 37 TC 10 Z9 10 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 DEC 1 PY 1997 VL 250 IS 2 BP 425 EP 431 DI 10.1111/j.1432-1033.1997.0425a.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK840 UT WOS:A1997YK84000027 PM 9428694 ER PT J AU Sathyamoorthy, N Wang, TTY AF Sathyamoorthy, N Wang, TTY TI Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE MCF-7 cells; daidzein; equol; pS2 expression; oestrogen receptor binding; cellular growth ID ESTROGEN-RECEPTOR; MENSTRUAL-CYCLE; GENISTEIN; PHYTOESTROGENS; INVITRO; WOMEN; LIGNANS; GROWTH; ENTEROLACTONE; STIMULATION AB The in vitro effects of two closely related phyto-oestrogens daidzein and equol on the oestrogen receptor positive human breast cancer cells MCF-7 were examined. There is differential metabolism of daidzein in humans, and the conversion of daidzein to equol by intestinal microbes occurs only in 30% of the population. The differential potency of these two compounds is thus of considerable importance since it may be likely that the relative risk of hormone-dependent cancers may be higher in 'non-responders'. In the present study, we compared the ability of both these compounds to induce mRNA expression of the oestrogen-responsive pS2 gene, to compete with oestradiol for binding to the oestrogen receptor (ER) and to affect cellular proliferation. Our studies demonstrate that equol is a 100-fold more potent than daidzein in stimulating an oestrogenic response. Equol was also more effective than daidzein in competing with H-3-oestradiol for binding to the ER. These results suggest that equol has a higher affinity for the ER. Both compounds stimulated the growth of MCF-7 cells in a concentration-dependent manner (10(-8)-10(-5) M). Although equol exhibits oestrogenic activity, exposure of MCF-7 cells to equol simultaneously with oestradiol was effective in reducing pS2 mRNA expression. This was not observed with daidzein. However, long-term exposure of MCF-7 cells to both daidzein and equol resulted in the downregulation of ER mRNA expression. (C) 1997 Elsevier Science Ltd. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Nutrit & Mol Regulat, Frederick, MD 21702 USA. RP Sathyamoorthy, N (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Nutrit & Mol Regulat, POB B, Frederick, MD 21702 USA. NR 33 TC 134 Z9 145 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1997 VL 33 IS 14 BP 2384 EP 2389 DI 10.1016/S0959-8049(97)00303-1 PG 6 WC Oncology SC Oncology GA YR888 UT WOS:000071541500033 PM 9616286 ER PT J AU Srinivasan, S Seaman, M Nemoto, Y Daniell, L Suchy, SF Emr, S DeCamilli, P Nussbaum, R AF Srinivasan, S Seaman, M Nemoto, Y Daniell, L Suchy, SF Emr, S DeCamilli, P Nussbaum, R TI Disruption of three phosphatidylinositol-polyphosphate 5-phosphotose genes from Saccharomyces cerevisiae results in pleiotropic abnormalities of vacuole morphology, cell shape, and osmohomeostasis SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE vacuole; phosphatidylinositol-phosphate; phosphatidylinositol-phosphate 5-phosphatase; synaptojanin; oculocerebrorenal syndrome ID PHOSPHOLIPID TRANSFER PROTEIN; ENDOSOME-LIKE COMPARTMENT; ACTIN CYTOSKELETON; YEAST GOLGI; INTERNALIZATION STEP; MULTIPLE ALIGNMENT; VESICLE FORMATION; INOSITOL; ENDOCYTOSIS; MUTANT AB As a result of the genome sequencing project in Saccharomyces cerevisiae, three open reading frames were found in the yeast genome that contain sequences with strong homology to all the domains conserved among the four mammalian phosphatidylinositol-phosphate 5-phosphatases: inpp5bp, ocrl1p, synaptojanin, and ship. In addition, all three yeast gene products shared with synaptojanin regions of homology to the SAC1 gene of yeast. Disruption of each of these genes singly and in pairs produced mutant strains that were viable but demonstrated variable phenotypes of abnormal vacuolar and plasma membrane morphology as well as increased sensitivity to osmotic stress. Total phosphatidylinositol-(4,5)-bisphosphate 5-phosphatase activity was reduced to varying degrees in each of the strains. No defect in carboxypeptidase Y sorting was seen in a processing and targeting assay. Abnormal actin cytoskeleton morphology was present in some of the strains carrying mutations in two of the genes. C1 NIH,LGDR,NHGRI,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,HOWARD HUGHES MED INST,SAN DIEGO,CA 92103. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT CELL BIOL,NEW HAVEN,CT 06510. FU NCI NIH HHS [CA46128, CA58689]; NIGMS NIH HHS [GM32703] NR 59 TC 82 Z9 83 U1 0 U2 7 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD DEC PY 1997 VL 74 IS 4 BP 350 EP 360 PG 11 WC Cell Biology SC Cell Biology GA YK843 UT WOS:A1997YK84300008 PM 9438131 ER PT J AU Pantaleo, G Soudeyns, H Demarest, JF Vaccarezza, M Graziosi, C Paolucci, S Daucher, M Cohen, OJ Denis, F Biddison, WE Sekaly, RP Fauci, AS AF Pantaleo, G Soudeyns, H Demarest, JF Vaccarezza, M Graziosi, C Paolucci, S Daucher, M Cohen, OJ Denis, F Biddison, WE Sekaly, RP Fauci, AS TI Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human immunodeficiency virus; AIDS; cytotoxic T cell; T cell receptor; lymph node ID PRIMARY HIV-1 INFECTION; PRIMARY IMMUNE-RESPONSE; VARIABLE REGION GENES; V-BETA REPERTOIRE; VACCINIA VIRUS; ANTIGEN PRESENTATION; EXPRESSION VECTOR; TYPE-1 INFECTION; CELL RECOGNITION; CHAIN AB Down-regulation of the initial burst of viremia during primary human immuno-deficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8(+) cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective downregulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection. C1 CHU Vaudois, Div Infect Dis, Dept Med, Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Pantaleo, G (reprint author), CHU Vaudois, Div Infect Dis, Dept Med, Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland. EM Giuseppe.Pantaleo@chuv.hospvd.ch RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 51 TC 38 Z9 38 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1997 VL 27 IS 12 BP 3166 EP 3173 DI 10.1002/eji.1830271213 PG 8 WC Immunology SC Immunology GA YQ647 UT WOS:000071409200012 PM 9464802 ER PT J AU Behar, TN Dugich-Djordjevic, MM Li, YX Ma, W Somogyi, R Wen, X Brown, E Scott, C McKay, RDG Barker, JL AF Behar, TN Dugich-Djordjevic, MM Li, YX Ma, W Somogyi, R Wen, X Brown, E Scott, C McKay, RDG Barker, JL TI Neurotrophins stimulate chemotaxis of embryonic cortical neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; cortex; migration; rat; TrkB ID TYROSINE PROTEIN-KINASE; NERVE GROWTH-FACTOR; CELL-MIGRATION; CEREBRAL-CORTEX; MESSENGER-RNAS; SPINAL-CORD; RECEPTOR; TRKB; EXPRESSION; CALCIUM AB During mammalian cortical development, neuronal precursors proliferate within ventricular regions then migrate to their target destinations in the cortical plate, where they organize into layers. In the rat, most cortical neuronal migration occurs during the final week of gestation (Bayer et al., 1991; Jacobson, 1991). At this time (E15-E21), reverse transcriptase-polymerase chain reaction demonstrated that cortical homogenates contain mRNA encoding brain derived neurotrophic factor (BDNF) and the catalytic form of its high-affinity receptor, TrkB. Immunocytochemistry and in situ hybridization of sections revealed that the catalytic TrkB receptors predominantly localize to regions containing migratory cells. Many TrkB+ cells exhibited the classic morphology of migrating neurons, suggesting that TrkB ligands play a role in cortical neuronal migration. We analysed whether TrkB ligands influence the motility of embryonic cortical cells (from E15-E21) using a quantitative in vitro chemotaxis assay. High-affinity TrkB ligands (BDNF and NT4/5) stimulated chemotaxis (directed migration) of embryonic neurons at concentrations ranging from 1 to 100 ng/ml. NT-3, a low-affinity TrkB ligand, only stimulated significant migration at high concentrations (greater than or equal to 100 ng/ml). Peak migration to BDNF was observed at gestational day 18 (E18). BDNF-induced chemotaxis was blocked by either tyrosine kinase inhibitor, K252a, or the Ca2+-chelator, BAPTA-AM, suggesting that BDNF-induces motility via autophosphorylation of TrkB receptor proteins and involves Ca2+-dependent mechanisms. BDNF-stimulation of increased cytosolic Ca2+ was confirmed with optical recordings of E18 cortical cells loaded with Ca2+ indicator dye. Thus, signal transduction through the TrkB receptor complex directs neuronal migration, suggesting that, in vivo, BDNF exerts chemotropic effects that are critical to morphogenesis of the cortex. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Behar, TN (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C02,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. NR 37 TC 68 Z9 70 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 1997 VL 9 IS 12 BP 2561 EP 2570 DI 10.1111/j.1460-9568.1997.tb01685.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZB439 UT WOS:000072461400007 PM 9517461 ER PT J AU Johnson, TP Jobe, JB ORourke, D Sudman, S Warnecke, RB Chavez, N ChapaResendez, G Golden, P AF Johnson, TP Jobe, JB ORourke, D Sudman, S Warnecke, RB Chavez, N ChapaResendez, G Golden, P TI Dimensions of self-identification among multiracial and multiethnic respondents in survey interviews SO EVALUATION REVIEW LA English DT Article ID ETHNIC-IDENTITY; QUESTIONNAIRES AB This article reports findings from a laboratory study designed to investigate self-identification among 69 multiracial and multiethnic women. Respondent reactions to two current questionnaire formats for collecting racial information and a third version that includes a multiracial response option were examined. Findings suggest that respondents' racial identification varies considerably across question formats and that persons of mixed heritage prefer a racial identification question that provides them, at a minimum with the opportunity to acknowledge their multiracial background. In addition, many respondents also expressed the desire to identify each of the specific groups that constitute their racial/ethnic background. C1 NIA,ADULT PSYCHOL DEV BRANCH,NIH,BETHESDA,MD 20892. RP Johnson, TP (reprint author), UNIV ILLINOIS,SURVEY RES LAB,CHICAGO,IL 60680, USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD DEC PY 1997 VL 21 IS 6 BP 671 EP 687 DI 10.1177/0193841X9702100602 PG 17 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA YK048 UT WOS:A1997YK04800002 ER PT J AU Whelan, PJ Pearson, KG AF Whelan, PJ Pearson, KG TI Comparison of the effects of stimulating extensor group I afferents on cycle period during walking in conscious and decerebrate cats SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE walking; group I afferent; reflex; cat ID LOW SPINAL CAT; INTERLIMB COORDINATION; FICTIVE LOCOMOTION; HINDLIMB; PHASE; VERTEBRATES; RESPONSES; PATHWAY; MUSCLE; REFLEX AB Previous studies have reported that stimulation of group I afferents from extensor muscles prolongs stance duration during walking in decerebrate cats. The main objective of this investigation was to determine whether this phenomenon occurs during walking in conscious cats. In conscious cats without lesions of the central nervous system (CNS), stimulation of group I afferents in the lateral gastrocnemius/soleus (LGS) nerve during stance prolonged extensor burst duration and increased the cycle period in five of seven animals. The mean increases in cycle period were modest, ranging from 6 to 22%. In five of six animals that walked both quadrupedally and bipedally at the same rate, the effects on cycle period were stronger during bipedal stepping (18% mean increase in cycle period compared with 9%). The stimulated nerves were transected and the experimental procedure was usually delayed in the conscious animals for 2-3 days following implantation of the stimulating electrodes. To assess whether chronic axotomy of the LGS nerve was a factor in the decreased effectiveness, four of the cats with chronic nerve section were decerebrated and their LGS nerves were stimulated after the animals began to spontaneously walk on a motorized treadmill. In all four of these animals, the effects of stimulating the chronically cut LGS nerve on the step cycle period became stronger following decerebration. However, these effects were not as strong as those produced when an acutely sectioned LGS nerve was stimulated. During both quadrupedal and bipedal walking, stimulation of the LGS nerve increased the amplitude of the medial gastrocnemius (MG) electromyogram. The augmented activity of the MG muscle contributed to an increased extension of the ankle during stimulated steps. C1 Univ Alberta, Dept Physiol, Edmonton, AB T6G 2H7, Canada. RP Pearson, KG (reprint author), NINDS, NIH, Lab Neurol Control, Bldg 49,49 Convent Dr,Room 3A50, Bethesda, MD 20892 USA. NR 33 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD DEC PY 1997 VL 117 IS 3 BP 444 EP 452 DI 10.1007/s002210050239 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YL926 UT WOS:000071008900011 PM 9438712 ER PT J AU Lobanoff, MC Kozhich, AT Mullet, DI Gerber, N Gery, I Chan, CC Whitcup, SM AF Lobanoff, MC Kozhich, AT Mullet, DI Gerber, N Gery, I Chan, CC Whitcup, SM TI Effect of gallium nitrate on experimental autoimmune uveitis SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE gallium nitrate; uveitis; experimental autoimmune uveitis; autoimmunity; eye; inflammation; animal model; retina; choroid; lymphocyte ID RATS; UVEORETINITIS; LYMPHOCYTE; INHIBITION; ANTIGEN AB Gallium nitrate (GN) has been shown to inhibit T cell-mediated inflammatory disease. The purpose of our study was to test the effect of gallium nitrate (GN) on experimental autoimmune uveitis (EAU). Experimental autoimmune uveitis was induced in male Lewis rats immunized with retinal S-antigen. Rats received subcutaneous injections of GN or saline one day prior to immunization and 1, 4, 7, 10, 13, 16, and 19 days after immunization. Ocular inflammation was graded clinically and histologically by masked observers, and in vitro assays of cell-mediated and humoral immunity were performed. GN significantly inhibited the development of EAU graded clinically (P = 0.001) and histologically (P = 0.002). Treatment with GN also resulted in a small (30-41%) decrease in the lymphocyte responses to retinal S-Antigen and a small (12-37 %) reduction in antibody production to S-antigen. These data show that GN suppresses the development of EAU, and inhibits both lymphocyte proliferative responses to antigen and antibody production. (C) 1997 Academic Press Limited. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD USA. Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA. RP Whitcup, SM (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10 Rm 10N 202, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 1997 VL 65 IS 6 BP 797 EP 801 DI 10.1006/exer.1997.0395 PG 5 WC Ophthalmology SC Ophthalmology GA YN549 UT WOS:000071179700008 PM 9441703 ER PT J AU Cheng, HR Almstrom, S Gimenez-Llort, L Chang, R Ogren, SO Hoffer, B Olson, L AF Cheng, HR Almstrom, S Gimenez-Llort, L Chang, R Ogren, SO Hoffer, B Olson, L TI Gait analysis of adult paraplegic rats after spinal cord repair SO EXPERIMENTAL NEUROLOGY LA English DT Article DE spinal cord; acidic fibroblast growth factor; peripheral serve graft; hindlimbs; stepping; fibrin glue; regeneration ID LOCOMOTOR FUNCTION; BRAIN-STEM; INJURY; RECOVERY; NEURONS; PROJECTIONS; REGENERATION; CAT AB This study presents a novel detailed method of analysis of rat gait and uses this method to demonstrate recovery of forward locomotion patterns in adult rats made paraplegic by surgical spinal cord transection slid subjected to a novel strategy for spinal cord repair, Six normal rats were compared to five animals in which the cord was transected at T8-T9, and a 5-mm segment of the spinal cord removed, and to seven animals in which, following spinal cord transection and removal of a spinal cord segment, multiple intercostal peripheral nerve bridges were implanted, rerouting pathways from white to gray matter in both directions. The implanted area was filled with fibrin glue containing acidic fibroblast growth factor Details of the repair strategy have been published (H. Cheng, Y. Cao, and L. Olson, 1996, Science 273: 510-513), Gait analysis was carried out 3 and 4 months after surgery and once in the normal animals, Animals were allowed to walk across a runway with a transparent floor. Each test consisted of five trials, and each trial was videorecorded from underneath. Using frame-by-frame play-back, individual footprints were then recorded regarding location and order of limb use, as well as step quality (degree of weight bearing, etc.). These data allowed measuring runway transit time, five different measures of step numbers, all possible temporal patterns of limb use, stride length, and base of support. Transected controls remained paralyzed in the hindlimbs with only occasional reflex hindlimb movements without weight bearing. Animals subjected to the full repair procedure were significantly faster than the controls, used their hindlimbs for 25-30% of the movements, and regained several of the specific limb recruitment patterns used by normal rats. Taken together the gait analysis data demonstrate remarkable recovery of coordinated gait in the repaired animals, which was significantly better than controls for all relevant parameters, while at the same time clearly inferior to normal rats for most of the examined parameters. We conclude that normal rats use a multitude of interchangeable step sequence patterns, and that our spinal cord repair strategy leads to recovery of some of these patterns following complete spinal cord transection, These data suggest functionally relevant neuronal communication across the lesion. (C) 1997 Academic Press. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Vet Gen Hosp Taipei, Inst Neurol, Dept Neurosurg, Taipei, Taiwan. Natl Yang Ming Univ, Div Surg, Taipei 112, Taiwan. NIDA, NIH, Baltimore, MD 20892 USA. RP Cheng, HR (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. NR 48 TC 81 Z9 82 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1997 VL 148 IS 2 BP 544 EP 557 DI 10.1006/exnr.1997.6708 PG 14 WC Neurosciences SC Neurosciences & Neurology GA YQ127 UT WOS:000071351200015 PM 9417831 ER PT J AU Fryer, RH Kaplan, DR Kromer, LF AF Fryer, RH Kaplan, DR Kromer, LF TI Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro SO EXPERIMENTAL NEUROLOGY LA English DT Article DE NGF; NT-3; NT-4/5; regeneration; trophic factor ID NERVE GROWTH-FACTOR; RETINAL GANGLION-CELLS; CHOLINERGIC AXONAL REGENERATION; TYROSINE KINASE RECEPTOR; MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTOR; ADULT-RAT; PERIPHERAL-NERVE; FACTOR PROMOTES; SCIATIC-NERVE AB The function of truncated trkB receptors during nervous system plasticity and regeneration is currently unknown. The extensive nonneuronal localization of truncated trkB-T1 receptors, coupled with their up-regulation by CNS glial cells in response to injury, has led to the speculation that these receptors may sequester BDNF and NT-4/5 to reduce their local availability and, thus, limit axonal sprouting, Conversely, trkB-T1 receptors could bind and present neurotrophins to injured axons and facilitate their regeneration in a manor analogous to that proposed for p75(NTR) receptors on Schwann cells, To address this issue, we used an in vitro coculture paradigm in which wild-type 3T3 NIH fibroblasts or two differ ent 3T3 cell clones stably expressing trkB-T1 receptors served as monolayer substrates upon which to evaluate the effect of trkB-T1 receptors on nonneuronal cells to influence neurotrophin (NGF, BDNF, NT-3, and NT-4/5)-induced neurite outgrowth from retinoic acid (RA)-treated SY5Y neuroblastoma cells. In these experiments, BDNF and NT-4/5 produce a strong phosphorylation of trk receptors on the RA-SY5Y cells and induce differentiation of the SY5Y cells (as measured by the development of neurofilament-positive neuritic processes), This ability of the trkB ligands to stimulate neurite outgrowth is dose dependent since increasing concentrations of BDNF (5, 25, and 100 ng/ml) result in an increased percentage of SY5Y cells developing neurites and in progressively longer neurites from SY5Y cells on the control 3T3 monolayers, In these experiments, BDNF and NT-4/5 induce the strongest neurite outgrowth, followed by NT-3 and then NGF. When trkB-T1 receptors are present on the 3T3 cell substratum bath BDNF- and NT-4/5-induced neurite extension from the SY5Y cells are strongly inhibited. In contrast, NGF-induced neurite growth is unaffected and NT-3-associated growth is somewhat reduced. These results suggest that the inhibitory effect of the trkB-T1 receptors on the nonneuronal cell substrates is selective for neurite outgrowth that is mediated via the trkB-kinase receptors on the neuroblastoma cells. This ability of trkB-T1 receptors on the nonneuronal substratum to inhibit BDNF-induced neurite outgrowth can be overcome by the addition of high concentrations of BDNF (1 mu g/ml). Binding assays using I-125-BDNF suggest that this inhibitory effect could be mediated via binding and internalization of BDNF by the trkB-T1 receptors on the 3T3 cells. These results provide strong support for the hypothesis that the up-regulation of trkB-T1 receptors on astrocytes following CNS lesions enhances the sequestration of the trkB ligands, BDNF and NT-4/5, at the site of reactive gliosis and, thus, contributes to the inhibition of CNS axonal regeneration from neurons expressing trkB-kinase receptors by removing their ligands from the extracellular environment. (C) 1997 Academic Press. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NCI, Eukaryot Signal Transduct Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Fryer, RH (reprint author), Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. FU NINDS NIH HHS [NS31445] NR 64 TC 98 Z9 101 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1997 VL 148 IS 2 BP 616 EP 627 DI 10.1006/exnr.1997.6699 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YQ127 UT WOS:000071351200021 PM 9417837 ER PT J AU Glowa, JR LeSage, M Stafford, D Vocci, F AF Glowa, JR LeSage, M Stafford, D Vocci, F TI Novel pharmacotherapies for cocaine abuse - 1995 to present SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE animal models; cocaine; drug abuse; pharmacology; self-administration ID PROGRESSIVE-RATIO SCHEDULE; D2 DOPAMINE ANTAGONIST; DELTA-OPIOID RECEPTORS; RHESUS-MONKEYS; INTRAVENOUS COCAINE; RADIOLIGAND-BINDING; CARBAMAZEPINE TREATMENT; BRAIN MEMBRANES; BEHAVIOR; IBOGAINE AB A new area in pharmaceutical development addresses the possibility that drug abuse can be treated with a medication. The advent of two successful treatments for drug abuse, nicotine patches and methadone, together with a growing cocaine abuse problem have sparked recent interest in developing a pharmacotherapy for cocaine abuse. Behavioural methods have been developed to the point where active compounds are likely to be identified, and a few potential agents have been found. Specific neurochemical effects of exposure to cocaine have suggested a number of additional targets, some of which have prompted the development of new ligands. Of those, drugs targeted at serotonergic, dopaminergic, GABAergic, opioid, and excitatory amino acid receptors have received the most attention. This article reviews recent advances in the development and testing of such agents, as well as patent applications (since 1995) for medications to treat drug abuse. C1 NIDA,MED DEV DIV,NIH,ROCKVILLE,MD 20827. RP Glowa, JR (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL & THERAPEUT,SHREVEPORT,LA 71130, USA. NR 64 TC 3 Z9 3 U1 1 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON, ENGLAND N6 5QJ SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD DEC PY 1997 VL 7 IS 12 BP 1459 EP 1476 DI 10.1517/13543776.7.12.1459 PG 18 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YJ965 UT WOS:A1997YJ96500005 ER PT J AU Bishop, JB Morris, RW Seely, JC Hughes, LA Cain, KT Generoso, WM AF Bishop, JB Morris, RW Seely, JC Hughes, LA Cain, KT Generoso, WM TI Alterations in the reproductive patterns of female mice exposed to xenobiotics SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article DE reproductive toxicology; female mice; litter size; fertility; oocytes; follicles; ovarian histology ID MOUSE AB Chemicals, by virtue of their varied interactions with biological molecules, are expected to differ in the way they may alter female reproduction. Reproductive toxicity may reflect effects either on the female germ cells or on various maternal processes such as ovulation, implantation, pregnancy, and parturition. In either case, the ultimate manifestation of chemical toxicity on female reproduction is a decrease in the number of normal young born. Very little information is available on the effects of chemicals that are nonhormonal in nature on the long-term ability of treated females to produce offspring. This report presents the results of long-term female total reproductive capacity (TRC) tests on 29 chemicals, including pharmaceuticals, pesticides, and alkylating and industrial agents. For each chemical, the minimum test involved an evaluation of the maximum tolerated dose administered as a single intraperitoneal injection. Females were single-pair mated with an untreated male for most of the female's reproductive life span (a minimum of 347 days posttreatment) and scored for the number of live births produced during this period. Confirmatory dominant lethal experiments or histological examinations for numbers of small follicles were carried out when mutagenic effects or cytotoxicity, respectively, were suspected as the basis for reduced fertility. Of the 29 chemicals studied, 17 had reproductive effects which may be grouped into one of three classes: (1) those that reduced the total number of young and litters per female, (2) those that reduced the total number of young but not of litters, and (3) those that had no significant effect on the total number of young produced but reduced the size of the first and/or second litters. The TRC provides a capacity for detecting a range of toxic insults upon female reproduction. Many of the chemicals were indeed shown to affect the reproductive performance of females through mutagenic and/or cytotoxic effects on follicles. In some cases, however, no causative mechanism could be identified for the observed reduction in reproductive performance. Nevertheless, with this report the number of chemicals tested by this TRC procedure has been quadrupled and the categories of chemicals tested have been substantially broadened. (C) 1997 Society of Toxicology. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Analyt Sci Inc, Durham, NC USA. PATHCO Inc, Res Triangle Pk, NC 27709 USA. Oak Ridge Natl Lab, Oak Ridge, TN 37830 USA. RP Bishop, JB (reprint author), NIEHS, POB 12233,B3-05, Res Triangle Pk, NC 27709 USA. EM bishop@niehs.nih.gov FU NIEHS NIH HHS [N01-ES-45379-03, N01-ES-65401, Y01-ES-20085] NR 21 TC 12 Z9 12 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD DEC PY 1997 VL 40 IS 2 BP 191 EP 204 DI 10.1006/faat.1997.2379 PG 14 WC Toxicology SC Toxicology GA YT071 UT WOS:000071561100004 PM 9441715 ER PT J AU Schmassmann, A Stettler, C Poulsom, R Tarasova, N Hirschi, C Flogerzi, B Matsumoto, K Nakamura, T Halter, F AF Schmassmann, A Stettler, C Poulsom, R Tarasova, N Hirschi, C Flogerzi, B Matsumoto, K Nakamura, T Halter, F TI Roles of hepatocyte growth factor and its receptor Met during gastric ulcer healing in rats SO GASTROENTEROLOGY LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; SCATTER FACTOR; MESSENGER-RNA; PRIMARY CULTURE; INCREASED EXPRESSION; GENE-EXPRESSION; DOWN-REGULATION; RENAL INJURY; WOUND REPAIR; LIVER AB Background & Aims: It is unclear which growth factors are primarily responsible for stimulating gastric ulcer healing. The roles of hepatocyte growth factor (HGF) and Met/HGF receptor during gastric ulcer healing were studied in rats. Methods: HGF and Met/HGF receptor were located and quantified by in situ hybridization and immunohistochemistry during experimental gastric ulcer healing. The in vivo effects of exogenous recombinant human HGF on cell proliferation and ulcer healing were assessed and compared with those of placebo and omeprazole treatment. Results: Compared with intact oxyntic mucosa, messenger RNA (mRNA) of HGF and met was substantially greater in the ulcerated region on days 3 and 15. HGF mRNA was located in stromal cells between the regenerative glands and in the arterial vessels of submucosal tissue, whereas met mRNA was located in the epithelial cells of the regenerative glands. After cryoinjury, immunoreactivity for the Met/HGF receptor was absent on day 3, reappeared on day 8, and was overexpressed on day 15. Exogenous recombinant human HGF had no effect on the ulcer healing parameters over days 3-8, but it did increase epithelial cell proliferation in the ulcer margin over days 8-15. Conclusions: These data suggest that HGF mediates specific tissue interactions between mesenchyme and epithelia during gastric ulcer healing. C1 IMPERIAL CANC RES FUND, HISTOPATHOL UNIT, LONDON, ENGLAND. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD USA. OSAKA UNIV, SCH MED, DIV BIOCHEM, BIOMED RES CTR, SUITA, OSAKA 565, JAPAN. RP Schmassmann, A (reprint author), UNIV HOSP BERN, INSERM, GASTROINTESTINAL UNIT, CH-3010 BERN, SWITZERLAND. NR 63 TC 69 Z9 70 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1997 VL 113 IS 6 BP 1858 EP 1872 DI 10.1016/S0016-5085(97)70005-2 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YH829 UT WOS:A1997YH82900010 PM 9394725 ER PT J AU Felzmann, T Ramsey, WJ Blaese, RM AF Felzmann, T Ramsey, WJ Blaese, RM TI Characterization of the antitumor immune response generated by treatment of murine tumors with recombinant adenoviruses expressing HSVtk, IL-2, IL-6 or B7-1 SO GENE THERAPY LA English DT Article DE gene therapy; adenovirus; herpes simplex virus thymidine kinase; costimulation; cytokine ID EXPERIMENTAL BRAIN-TUMORS; INTRATHECAL GENE-THERAPY; IN-VIVO; COLON-CARCINOMA; MELANOMA-CELLS; COSTIMULATION; INVIVO; CANCER; REGRESSION; METASTASES AB In a cancer gene therapy model recombinant adenoviruses expressing the herpes simplex virus thymidine kinase (HSVtk) gene were injected into tumors in situ, either alone or in combination with adenoviruses (Avs) engineered to express IL-2, IL-6 or the costimulatory molecule. B7-1, HSVtk phosphorylates the prodrug ganciclovir, thus converting it into an antimetabolite which kills not only HSVtk expressing cells, but also by the 'bystander effect, neighboring untransduced tumor cells. The tumors regressed in 80% of mice upon AvTK/ganciclovir treatment; combinations with AvIL-2, AvIL-6, or AvB7-1 did not improve these results. Cured mice were protected from further challenge with wild-type tumor but not from challenges with an unrelated syngeneic tumor cell line. Since cytotoxic T lymphocyte responses in this tumor model were weak, we analyzed cytokine secretion from spleen cells of treated animals. The best correlate of antitumor immunity in this model was enhanced secretion of GM-CSF, while secretion of IL-2, IL-6 and IFN gamma was also frequently increased but not as consistently. The enhanced IFN gamma secretion associated with unchanged IL-4 secretion suggests that AvTK treatment results in a predominantly Th1-mediated antitumor immune response. C1 NHGRI,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD. NR 35 TC 35 Z9 35 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 1997 VL 4 IS 12 BP 1322 EP 1329 DI 10.1038/sj.gt.3300533 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YK547 UT WOS:A1997YK54700007 PM 9472556 ER PT J AU Sonoda, G Palazzo, J duManoir, S Godwin, AK Feder, M Yakushiji, M Testa, JR AF Sonoda, G Palazzo, J duManoir, S Godwin, AK Feder, M Yakushiji, M Testa, JR TI Comparative genomic hybridization detects frequent overrepresentation of chromosomal material from 3q26, 8q24, and 20q13 in human ovarian carcinomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID COPY NUMBER; GENE AMPLIFICATION; DNA-SEQUENCES; BREAST-CANCER; BRCA1 GENE; LOW-GRADE; TUMORS; HETEROZYGOSITY; LOSSES; ABERRATIONS AB We used comparative genomic hybridization (CGH) to identify recurrent chromosomal imbalances in tumor DNA from 25 malignant ovarian carcinomas and two ovarian tumors of low malignant potential (LMP). Many of the carcinoma specimens displayed numerous imbalances. The most common sites of copy number increases, in order of frequency, were 8q24.1, 20q13.2-qter, 3q26.3-qter, 1q32, 20p, 9p21-pter, and 12p. DNA amplification was identified in 12 carcinomas (48%). The most frequent sites of amplification were 8q24.1-24.2, 3q26.3, and 20q13.2-qter. Other recurrent; sites of amplification included 7q36, 17q25, and 19q13.1-13.2. The most frequent sites of copy number decreases were 5q21, 9q, 17p, 17q12-21, 4q26-31, 16q, and 22q. Underrepresentation of 17p was observed in six of 16 stage III/IV tumors, but in none of seven stage I/II tumors, suggesting that this change may be a late event associated with the transition of ovarian carcinomas to a more metastatic disease. Overrepresentation of 3q26.3-qter, 5p14-pter, 8q24.1, 9p21-pter, 20p, and 20q13.2-qter and underrepresentation of 4q26-31 and 17q12-21 also tended to be more common in advanced-stage tumors. All ten grade 3 rumors had copy number increases involving 8q24.1, compared to only three of nine grade 2 tumors. Overrepresentation of 3q26.3-qter and 20q13.2-qter was also observed at a higher frequency in high-grade tumors. One of the two LMP tumors displayed chromosomal alterations, which consisted of overrepresentation of 5p and 9p only. Taken collectively, these findings and data from other CGH studies of ovarian cancers define a set of small chromosome segments that are consistently over- or underrepresented and, thus, highlight sites of putative oncogenes and tumor suppressor genes chat contribute to the pathogenesis of these highly malignant neoplasms. (C) 1997 Wiley-Liss, Inc. C1 FOX CHASE CANC CTR,SECT MOL CYTOGENET,DEPT MED ONCOL,PHILADELPHIA,PA 19111. THOMAS JEFFERSON UNIV,SCH MED,KIMMEL CANC CTR,DEPT PATHOL,PHILADELPHIA,PA 19107. NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD. KURUME UNIV,SCH MED,DEPT OBSTET & GYNECOL,FUKUOKA,JAPAN. FU NCI NIH HHS [CA-06927] NR 52 TC 174 Z9 175 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1997 VL 20 IS 4 BP 320 EP 328 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YJ557 UT WOS:A1997YJ55700002 PM 9408747 ER PT J AU Barlund, M Tirkkonen, M Forozan, F Tanner, MM Kallioniemi, O Kallioniemi, A AF Barlund, M Tirkkonen, M Forozan, F Tanner, MM Kallioniemi, O Kallioniemi, A TI Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DERMATOFIBROSARCOMA PROTUBERANS; DNA-SEQUENCES; CHROMOSOME-17; LOSSES; CARCINOMAS; GAINS; IDENTIFICATION; PATTERNS; TUMORS AB Studies by comparative genomic hybridization (CGH) have defined a chromosomal site at 17q22-q24 that is often overrepresented in breast cancer, neuroblastoma, and several other tumor types. Due to the limited resolution and dynamic range of CGH, it remains unclear whether this gain reflects high-level amplification of small subregion(s) or low-level gain of most of the distal 17q. We used 32 physically mapped 17q probes to construct more accurate copy number profiles for 14 breast cancer cell lines by interphase fluorescence in situ hybridization (FISH). Six cell lines (43%) showed an increased copy number of the 17q22-q24 region by CGH, and seven (50%) by FISH. FISH copy number profiles had a substantially higher dynamic range than did CGH profiles. FISH revealed two independent, highly amplified regions (A and B) at 17q23, separated by about 5 Mb of non-amplified DNA, These regions were distinctly telomeric from the ERBB2 gene locus. However, region A was often co-amplified with ERBB2, whereas B was amplified in cell lines that showed no ERBB2 amplification. We conclude that distal 17q gains recently discovered in breast cancer by CGH are due to high-level amplifications of two different regions at 17q23. This chromosomal region has previously been reported to undergo allelic loss and therefore was thought to harbor a tumor suppressor gene. The present FISH data provide support for the presence, and a starting point for the positional isolation, of 17q23 genes whose upregulation by amplification may play a role in the progression of breast cancer and many other tumor types. (C) 1997 Wiley-Liss, Inc. C1 NIH,CANC GENET LAB,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV TAMPERE,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. TAMPERE UNIV HOSP,TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 22 TC 81 Z9 81 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1997 VL 20 IS 4 BP 372 EP 376 DI 10.1002/(SICI)1098-2264(199712)20:4<372::AID-GCC8>3.0.CO;2-Z PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YJ557 UT WOS:A1997YJ55700008 PM 9408753 ER PT J AU Mahlamaki, EH Hoglund, M Gorunova, L Karhu, R Dawiskiba, S AndrenSandberg, A Kallioniemi, OP Johansson, B AF Mahlamaki, EH Hoglund, M Gorunova, L Karhu, R Dawiskiba, S AndrenSandberg, A Kallioniemi, OP Johansson, B TI Comparative genomic hybridization reveals frequent gains of 20q, 8q, 11q, 12q, and 17q, and losses of 18q, 9p, and 15q in pancreatic cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID 3P14.2 FRAGILE SITE; C-KI-RAS; CHROMOSOME-ABNORMALITIES; DNA-SEQUENCES; BREAST-CANCER; ADENOCARCINOMA; GENE; CARCINOMAS; TUMORS; AMPLIFICATION AB Comparative genomic hybridization (CCH) was used to screen for genomic imbalances in 24 exocrine pancreatic carcinomas, including 11 low-passage cell lines (4-8 subcultures) and 13 uncultured samples. Aberrations were found in all cell lines and in seven of the 13 biopsies. The most frequent changes in the cell lines were gains of 20q (91%), 11q (64%), 17q (64%), 19q (64%), 8q, 12p, 14q, and 20p (55%), and losses of 18q (100%), 9p (91%), 15q (73%), 21q (64%), 3p (55%), and 13q (55%). High-level gains (tumor to normal ratio over 1.5) were detected at 3q, 6p, 7q, 8q, 12p, 19q, and 20q. Among the tumor biopsies, overrepresentations of 7p and 8q were most common (31%), followed by 5p, 5q, 11p, 11q, 12p, and 18q (23%), whereas the most frequent losses involved 18p and 18q (31%) and 6q and 17p (23%). The genetic changes in nine samples obtained from metastatic lesions did not differ significantly from those in 15 primary carcinomas. Most of the gains and losses detected in this CGH study correspond well to those identified in previous cytogenetic and molecular genetic investigations of pancreatic carcinomas. However, frequent gain of 12p and loss of 15q have not been previously reported. Molecular genetic analyses Of these chromosome arms are warranted, and may lead to the discovery of novel genes important in pancreatic carcinogenesis. (C) 1997 Wiley-Liss, Inc. C1 UNIV LUND HOSP,DEPT CLIN GENET,S-22185 LUND,SWEDEN. UNIV LUND HOSP,DEPT PATHOL & CYTOL,S-22185 LUND,SWEDEN. UNIV LUND HOSP,DEPT SURG,S-22185 LUND,SWEDEN. NIH,NATL HUMAN GENOME RES INST,CANC GENET LAB,BETHESDA,MD. UNIV TAMPERE,INST MED TECHNOL,FIN-33101 TAMPERE,FINLAND. TAMPERE UNIV HOSP,CANC GENET LAB,TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 44 TC 112 Z9 112 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1997 VL 20 IS 4 BP 383 EP 391 DI 10.1002/(SICI)1098-2264(199712)20:4<383::AID-GCC10>3.0.CO;2-O PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YJ557 UT WOS:A1997YJ55700010 PM 9408755 ER PT J AU McDonald, JP Levine, AS Woodgate, R AF McDonald, JP Levine, AS Woodgate, R TI The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism SO GENETICS LA English DT Article ID INTACT YEAST-CELLS; RECA PROTEIN; MUTAGENESIS PROTEINS; BINDING SEQUENCE; STRANDED-DNA; UV; POLYMERASE; MUTATIONS; TRANSFORMATION; PURIFICATION AB Damage-inducible mutagenesis in prokaryotes is largely dependent upon the activity of the UmuD'C-like proteins. Since many DNA repair processes are structurally and/or functionally conserved between prokaryotes and eukaryotes, we investigated the role of RAD30, a previously uncharacterized Saccharomyces cerevisiae DNA repair gene related to the Escherichia coli dinB, umuC and S. cerevisiae REV1 genes, in UV resistance and UV-induced mutagenesis. Similar to its prokaryotic homologues, RAD30 was found to be damage inducible. Like many S. cerevisiae genes involved in error-prone DNA repair, epistasis analysis clearly places RAD30 in the XAD6 group and rad30 mutants display moderate UV sensitivity reminiscent of rev mutants. However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of the RAD6 epistasis group. These findings suggest that RAD30 participates in a novel error-free repair pathway dependent on RAD6 and RAD18, but independent of REV1, REV3 REV7 and RAD5. C1 NICHHD,NIH,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. NR 56 TC 256 Z9 261 U1 1 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1997 VL 147 IS 4 BP 1557 EP 1568 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA YK654 UT WOS:A1997YK65400007 PM 9409821 ER PT J AU Aseev, MV Shawi, A Dean, M Baranov, VS AF Aseev, MV Shawi, A Dean, M Baranov, VS TI Population frequencies of the CKR5 mutant allele of the chemokine receptor gene responsible for HIV infection SO GENETIKA LA Russian DT Article ID HUNTINGTONS-DISEASE; MUTATIONS; MODEL AB Recently, it was shown that a 32-bp deletion in the CKR5 macrophage chemokine receptor gene produced resistance to HIV infection. Frequencies of the CKR5 mutant allele in Russians, Tatars, Uzbeks, Kazakhs, Azrbaijanians, Uigurts, Tuvinians, and Georgians estimated by means of the PCR technique were equal to 0.13, 0.12, 0.85, 0.06, 0.05, 0.04, 0.03, and 0.00, respectively. While the theoretically expected frequency of deletion homozygotes in Russians and Tatars was 1.7%, none of such homozygotes were detected among the 90 persons examined. The data suggested that about 25% of the population in northwestern Russia is highly resistant to HIV infection. C1 Russian Acad Med Sci, Ott Inst Obstet & Gynecol, St Petersburg 199034, Russia. NIH, Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Aseev, MV (reprint author), Russian Acad Med Sci, Ott Inst Obstet & Gynecol, St Petersburg 199034, Russia. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 11 TC 6 Z9 7 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0016-6758 J9 GENETIKA+ JI Genetika PD DEC PY 1997 VL 33 IS 12 BP 1724 EP 1726 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA YT092 UT WOS:000071563200016 PM 9493032 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: The Washington University Genome Sequencing Center's Web site SO GENOME RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD DEC PY 1997 VL 7 IS 12 BP 1118 EP 1121 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YP300 UT WOS:000071263100003 PM 9414317 ER PT J AU Reddy, PH Stockburger, E Gillevet, P Tagle, DA AF Reddy, PH Stockburger, E Gillevet, P Tagle, DA TI Mapping and characterization of novel (CAG)(n) repeat cDNAs from adult human brain derived by the oligo capture method SO GENOMICS LA English DT Article DE trinucleotide repeats; CAG expansion; EST; neurodegeneration; brain expression ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; FAMILIAL PARKINSONS-DISEASE; DOMINANT CEREBELLAR ATAXIAS; SEVERE BIPOLAR DISORDER; HAW-RIVER-SYNDROME; TRINUCLEOTIDE REPEATS; CAG REPEAT; MYOTONIC-DYSTROPHY; TRIPLET REPEAT; SUSCEPTIBILITY LOCUS AB The expansion of a (CAG)(n) trinucleotide repeat has been associated with at least eight neurological disorders in which the repeats code for polyglutamine in the protein. To identify additional genes that possess (CAG)(n) repeats, single-stranded cDNA clones derived from adult human brain were screened using biotinylated oligonucleotide (CAG)(8), and the hybridizing complexes were isolated with strepavidin-coated paramagnetic beads. A total of 119 cDNA clones were isolated and initially characterized by end sequencing. BLAST homology searches were used to reduce redundancies with overlapping clones and to eliminate those that show sequence identity with previously published cDNAs with triplet repeats. Only cDNA clones with more than five CAG repeats were pursued for analysis. A total of 19 novel cDNAs were further characterized by determining chromosomal assignments using the Stanford G3 and Genebridge radiation-reduced hybrid mapping panels. Transcript sizes and tissue expression patterns were determined by Northern blot analysis. Two of 19 clones showed specific or high expression in brain. These cDNAs are ideal candidate genes for other neurodegenerative disorders, such as spinocerebellar ataxia types 5 and 7, and may also be implicated in psychiatric diseases such as bipolar affected disorder and schizophrenia. (C) 1997 Academic Press. C1 NHGRI,GENET & MOL BIOL BRANCH,NIH,BETHESDA,MD 20892. GEORGE MASON UNIV,INST BIOSCI BIOINFORMAT & BIOTECHNOL,MANASSAS,VA 22030. NR 61 TC 12 Z9 13 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 1 PY 1997 VL 46 IS 2 BP 174 EP 182 DI 10.1006/geno.1997.5044 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YL016 UT WOS:A1997YL01600002 PM 9417904 ER PT J AU Perry, CL Sellers, DE Johnson, C Pedersen, S Bachman, KJ Parcel, GS Stone, EJ Luepker, RV Wu, M Nader, PR Cook, K AF Perry, CL Sellers, DE Johnson, C Pedersen, S Bachman, KJ Parcel, GS Stone, EJ Luepker, RV Wu, M Nader, PR Cook, K TI The child and adolescent trial for cardiovascular health (CATCH): Intervention, implementation, and feasability for elementary schools in the United States SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID PHYSICAL-ACTIVITY; RISK-FACTORS; PROMOTION; EDUCATION; DIET; OUTCOMES; BEHAVIOR; DISEASE; ISSUES AB The Child and Adolescent Trial for Cardiovascular Health (CATCH) was the largest school-based field trial ever sponsored by the National Institutes of Health. The trial demonstrated positive changes in the school food service and physical education program, as well as in students' cardiovascular health behaviors. Because the CATCH intervention programs were implemented in 56 schools (in four states) that were typical of schools throughout the United States, their reception by schools and degree of implementation provide evidence about their feasibility for schools nationally. Extensive process evaluation data were collected from students, teachers, school food service personnel, and physical education specialists throughout the three school years of the CATCH intervention. Four of the CATCH programs-school food service, physical education, classroom curricula, and home programs-were assessed over the three school years. The process data provide information on participation, dose, fidelity, and compatibility of the CATCH programs in the intervention schools for these programs. High levels of participation, dose, fidelity, and compatibility were observed for the four programs during the 3 school years. CATCH emerges as a model of a feasible multilevel health promotion program to improve eating and exercise behaviors for elementary schools in the United States. C1 EDUC DEV CTR,NEWTON,MA. TULANE UNIV,DEPT COMMUNITY HLTH SCI,NEW ORLEANS,LA 70118. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV CALIF SAN DIEGO,DEPT PEDIAT,DIV COMMUNITY PEDIAT,SAN DIEGO,CA 92103. UNIV TEXAS,HLTH SCI CTR,CTR HLTH PROMOT RES & DEV,HOUSTON,TX. NHLBI,BETHESDA,MD 20892. RP Perry, CL (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55455, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39906, U01-HL-39927] NR 34 TC 59 Z9 59 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD DEC PY 1997 VL 24 IS 6 BP 716 EP 735 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YH062 UT WOS:A1997YH06200006 PM 9408786 ER PT J AU Pawlosky, RJ Flynn, BM Salem, N AF Pawlosky, RJ Flynn, BM Salem, N TI The effects of low dietary levels of polyunsaturates on alcohol-induced liver disease in rhesus monkeys SO HEPATOLOGY LA English DT Article ID HIGH-FAT DIET; LIPID-PEROXIDATION; RAT-LIVER; ETHANOL; ACID; PATHOGENESIS; FIBROGENESIS; NUTRITION; CIRRHOSIS; FIBROSIS AB Rhesus monkeys that were maintained on a diet containing low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the total caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg(-1) d(-1)) over a period of 3 years, In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes. The amount of alcohol consumed correlated positively with plasma lipid peroxidation products, 4-hydroxynonenal (4-HNE) and 8-isoprostane F-2 alpha, and negatively with 20:4n6 and 22:6n3 levels, These findings imply that alcoholics who also have a marginal intake of essential fatty acids and antioxidants in their diets may be at an increased risk of developing liver disease. C1 NCI,DIR,BETHESDA,MD 20892. RP Pawlosky, RJ (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,12420 PARKLAWN DR,ROOM 158,ROCKVILLE,MD 20852, USA. NR 37 TC 24 Z9 24 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1997 VL 26 IS 6 BP 1386 EP 1392 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YK772 UT WOS:A1997YK77200003 PM 9397975 ER PT J AU Factor, VM Jensen, MR Thorgeirsson, SS AF Factor, VM Jensen, MR Thorgeirsson, SS TI Coexpression of c-myc and transforming growth factor alfa in the liver promotes early replicative senescence and diminishes regenerative capacity after partial hepatectomy in transgenic mice SO HEPATOLOGY LA English DT Article ID UNSCHEDULED DNA-SYNTHESIS; FACTOR-ALPHA; CELL-CYCLE; MOLECULAR MECHANISMS; SIGNAL-TRANSDUCTION; DIETARY RESTRICTION; HEPATOCYTE GROWTH; MESSENGER-RNA; MAMMARY-GLAND; FACTOR-BETA AB We have recently shown that overexpression of c-myc and transforming growth factor alpha (TGF-alpha) in the liver of double-transgenic mice results in severe DNA damage, aberrant hepatic growth, and development of tumors at a much younger age than that observed in c-myc single-transgenic mice. We now report that double-transgenic TGF-alpha/c-myc hepatocytes rapidly lose their ability to proliferate upon mitogenic stimulation following partial hepatectomy (PH). At 4 weeks of age, the overall rate of bromodeoxyuridine (BrdU) incorporation following PH was comparable in c-myc and TGF-alpha/c-myc livers and exceeded that seen in wild-type (WT) mice, However, by 10 weeks of age, c-myc single-transgenic hepatocytes showed proliferative advantages over the WT cells, whereas TGF-alpha/c-myc double-transgenic hepatocytes had a decreased capacity to proliferate upon mitogenic stimulation. This decreased proliferative response was accompanied by a reduction in the total fraction of proliferating hepatocytes, as well as by a decline in the induction of cyclin A, cyclin B, and cdc2 gene expression, These data show that constitutive coexpression of c-myc and TGF-alpha accelerates age-related loss in the regenerative potential following PH, and suggest that early replicative senescence of differentiated hepatocytes may have a role in providing a selective growth advantage to initiated cell populations in this model. C1 NCI,EXPT CARCINOGENESIS LAB,DBS,NIH,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 77 TC 33 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1997 VL 26 IS 6 BP 1434 EP 1443 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YK772 UT WOS:A1997YK77200011 PM 9397983 ER PT J AU Iimuro, Y Gallucci, RM Luster, MI Kono, H Thurman, RG AF Iimuro, Y Gallucci, RM Luster, MI Kono, H Thurman, RG TI Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat SO HEPATOLOGY LA English DT Article ID ALCOHOLIC LIVER-DISEASE; FACTOR-ALPHA; INTERFERON-GAMMA; KUPFFER CELLS; INJURY; INTERLEUKIN-1; ACTIVATION; INFUSION; HEPATOTOXICITY; NEUTROPHILS AB Tumor necrosis factor (TNF) alpha, a pivotal cytokine involved in inflammation, is produced primarily by Kupffer cells in the liver, It has been shown that inactivation of Kupffer cells prevents alcohol-induced liver injury; therefore, the purpose of this study was to determine if neutralizing anti-TNF-alpha antibody is also effective, Male Wistar mts were exposed to ethanol (11 to 12 g.kg(-1).d(-1)) continuously for up to 4 weeks via intragastric feeding using an enteral feeding model, Before ethanol exposure, polyclonal anti-mouse TNF-alpha rabbit serum was injected (2.0 mg/kg intravenously), There were no significant differences in body weight, mean ethanol concentration, or cyclic patterns of ethanol in urine when ethanol-and ethanol plus antibody-treated groups were compared, Expression of TNF-alpha and macrophage inflammatory protein 2 (MIP-2) messenger RNA (mRNA), determined using reverse transcription-polymerase chain reaction, was three-to fourfold higher in livers of ethanol-treated rats than in those of rats fed an ethanol-free, high-fat control diet. In addition, MIP-2 levels were also elevated when detected by Northern blot analysis. Anti-TNF-alpha antibody did not affect expression of mRNA for interleukin (IL) 1 alpha, IL-6, transforming growth factor beta(1), or TNF-alpha, However, MIP-2. mRNA expression, which is regulated by TNF-alpha, was decreased significantly by anti-TNF-alpha antibody treatment, Serum aspartate transaminase levels were elevated in ethanol-treated rats to 136 +/- 12 IU/L after 4 weeks but only reached 90 +/- 5 IU/L (P < .05) in rats treated with anti-TNF-alpha antibody. The hepatic inflammation and necrosis observed in ethanol-fed rats were attenuated significantly by antibody treatment, and steatosis was not, These results support the hypothesis that TNF-alpha plays an important role in inflammation and necrosis in alcohol-induced liver injury and that treatment with anti-TNF-alpha antibody may be therapeutically useful in this disease. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. NIEHS,IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. FU NIAAA NIH HHS [AA-09516, AA-03624] NR 53 TC 373 Z9 376 U1 2 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1997 VL 26 IS 6 BP 1530 EP 1537 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YK772 UT WOS:A1997YK77200022 PM 9397994 ER PT J AU Tacke, M Schmolke, S Schlueter, V Sauleda, S Esteban, JI Tanaka, E Kiyosawa, K Alter, HJ Schmitt, U Hess, G OfenlochHaehnle, B Engel, AM AF Tacke, M Schmolke, S Schlueter, V Sauleda, S Esteban, JI Tanaka, E Kiyosawa, K Alter, HJ Schmitt, U Hess, G OfenlochHaehnle, B Engel, AM TI Humoral immune response to the E2 protein of hepatitis G virus is associated with long-term recovery from infection and reveals a high frequency of hepatitis G virus exposure among healthy blood donors SO HEPATOLOGY LA English DT Article ID A-E HEPATITIS; C VIRUS; MOLECULAR-CLONING; HCV INFECTION; GLYCOPROTEIN; ENVELOPE; MARKER; ORGANIZATION; MAINTENANCE; SEQUENCE AB The second envelope protein (E2) of the hepatitis G virus (HGV) was expressed in Chinese hamster ovary (CHO) cells and showed a molecular weight of approximately 60 to 70 kd, with 15 to 25 kd of the size contributed by N-linked glycosylation. An enzyme-linked immunosorbent assay (ELISA) using HGV-E2 was developed to test for antibodies to this protein (anti-E2) in human sera. High sensitivity was achieved by developing monoclonal antibodies (mAbs) to HGV-EZ, which were used as capture antibodies in the ELISA. Our studies revealed that 16% of healthy Spanish blood donors were exposed to HGV, indicating that additional routes of viral transmission besides parenteral exposure might exist. An even higher prevalence of exposure to HGV (52%-73%) was found in several groups at risk of parenteral exposure to infectious agents, i.e., intravenous drug users, transfusion history, hemophiliacs, and hepatitis C virus (HCV)-positive patients. Most anti-E2-positive patients were HGV-RNA-negative and vice versa, indicating an !inverse correlation of these two viral markers. A panel of 16 posttransfusion patients followed for up to 16 years revealed that patients who develop an anti-E2 response become HGV-RNA-negative, while patients who do not develop anti-E2 are persistently infected. Immunity to HGV seems to be long-lasting, because circulating antibody to E2 could still be detected 14 years after seroconversion. Sequence comparisons showed that E2 is highly conserved among isolates collected worldwide, indicating that immune escape variants are not common in HGV infections. This reflects on a molecular level why HGV infections usually are cleared spontaneously by the host. However, possible mechanisms of HGV persistence, as found in some patients, remain to be elucidated. C1 UNIV BARCELONA,HOSP GEN VALLE HEBRON,LIVER UNIT,BARCELONA,SPAIN. SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,MATSUMOTO,NAGANO 390,JAPAN. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP Tacke, M (reprint author), BOEHRINGER MANNHEIM GMBH,R&D INFECT DIS,NONNENWALD 2,D-82372 PENZBERG,GERMANY. NR 28 TC 92 Z9 95 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1997 VL 26 IS 6 BP 1626 EP 1633 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YK772 UT WOS:A1997YK77200036 PM 9398008 ER PT J AU Issaragrisil, S Kaufman, D Shapiro, S Leaverton, P Young, NS AF Issaragrisil, S Kaufman, D Shapiro, S Leaverton, P Young, NS TI Predicting the risk of tumor recurrence following transplantation for hepatocellular carcinoma - Reply SO HEPATOLOGY LA English DT Letter C1 BOSTON UNIV,SCH MED,SLOANE EPIDEMIOL UNIT,BOSTON,MA 02118. UNIV S FLORIDA,SCH PUBL HLTH,TAMPA,FL. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP Issaragrisil, S (reprint author), MAHIDOL UNIV,SIRIRAJ HOSP,DEPT MED,DIV HEMATOL,BANGKOK 10700,THAILAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1997 VL 26 IS 6 BP 1689 EP 1689 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YK772 UT WOS:A1997YK77200052 ER PT J AU Aida, K Tawata, M Negishi, M Onaya, T AF Aida, K Tawata, M Negishi, M Onaya, T TI Mouse glycine N-methyltransferase is sexually dimorphic and regulated by growth hormone SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT Satellite Symposium on the Role of Adhesion Molecules in Diabetes Mellitus, of the 32nd Annual Meeting of the EASD CY SEP 01, 1996 CL VIENNA, AUSTRIA SP European Assoc Study Diabet DE growth hormone; mouse glycine N-methyltransferase; sexual; dimorphism ID FOLATE-BINDING-PROTEIN; LIVER; RAT; METABOLISM; SEQUENCE; ENZYMES; GENES; MICE AB The secretion pattern of putuitary growth hormone (GH) in rodents is sexually dimorphic and regulates the expression of some hepatic genes. We report cloning of mouse glycine N-methyltransferase (GNMT) cDNA. The mouse GNMT mRNA is expressed at much lower levels in male than in female livers. Hypophysectomy in male mice resulted in as a high level of the expression as in female mice. Treatment with GH of hypophysectomized male mice twice a day for 5 days decreased the expression. These results indicate that the sex difference of the mouse GNMT expression is regulated by GH secretion patterns. C1 Yamanashi Med Univ, Dept Internal Med 3, Tamaho, Yamanashi 40938, Japan. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Yamanashi Med Univ, Dept Internal Med 3, Tamaho, Yamanashi 40938, Japan. NR 24 TC 28 Z9 29 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 1997 VL 29 IS 12 BP 646 EP 649 DI 10.1055/s-2007-978982 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YT137 UT WOS:000071568300013 PM 9497905 ER PT J AU Kang, S Rosenberg, M Ko, VD Biesecker, LG AF Kang, S Rosenberg, M Ko, VD Biesecker, LG TI Gene structure and allelic expression assay of the human GLI3 gene SO HUMAN GENETICS LA English DT Article ID GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; PALLISTER-HALL SYNDROME; EXTRA-TOES XT; MUTATION ADD; LINKAGE; REGION; CONTIG AB The GLI3 gene encodes a putative zinc finger transcription factor that is important in early vertebrate development. Haploinsufficiency of this gene has been associated with the Greig cephalopolysyndactyly syndrome and truncation mutations cause Pallister-Hail syndrome. in the course of studies to determine the etiology of Pallister-Hall syndrome, we required knowledge of the fine structure of GLI3 to perform detailed genetic and physical mapping and mutation screening of this gene. The coding region of GLI3 is composed of 14 exons, including a large exon of more than 2500 bp. In addition, the gene contains two intragenic dinucleotide repeats, and four single-base pair polymorphisms in the coding region. We have used these coding region polymorphisms to design an allele-specific expression study that will be useful for studying patients with Greig cephalopolysyndactyly syndrome. Ln addition, GLI3 should be considered a candidate gene for related developmental anomalies of humans, Such hypotheses will be more readily addressed with the availability of the fine structure of the gene and the allele-expression assay. C1 NIH, NATL HUMAN GENOME RES INST, LAB GENET DIS RES, BETHESDA, MD 20892 USA. NR 23 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1997 VL 101 IS 2 BP 154 EP 157 DI 10.1007/s004390050605 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YJ560 UT WOS:A1997YJ56000007 PM 9402960 ER PT J AU Schrock, E Veldman, T Padilla-Nash, H Ning, Y Spurbeck, J Jalal, S Shaffer, LG Papenhausen, P Kozma, C Phelan, MC Kjeldsen, E Schonberg, SA O'Brien, P Biesecker, L du Manoir, S Ried, T AF Schrock, E Veldman, T Padilla-Nash, H Ning, Y Spurbeck, J Jalal, S Shaffer, LG Papenhausen, P Kozma, C Phelan, MC Kjeldsen, E Schonberg, SA O'Brien, P Biesecker, L du Manoir, S Ried, T TI Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities SO HUMAN GENETICS LA English DT Article ID INSITU SUPPRESSION HYBRIDIZATION; FLUORESCENCE; LEUKEMIA; CELLS AB Karyotype analysis by chromosome banding is the standard method for identifying numerical and structural chromosomal aberrations in pre-and postnatal cytogenetics laboratories. However, the chromosomal origins of markers, subtle translocations, or complex chromosomal rearrangements are often difficult to identify with certainty. We have developed a novel karyotyping technique, termed spectral karyotyping (SKY), which is based on the simultaneous hybridization of 24 chromosome-specific painting probes labeled with different fluorochromes or fluorochrome combinations. The measurement of defined emission spectra by means of interferometer-based spectral imaging allows for the definitive discernment of all human chromosomes in different colors, Here, we report the comprehensive karyotype analysis of 16 samples from different cytogenetic laboratories by merging conventional cytogenetic methodology and spectral karyotyping. This approach could become a powerful tool for the cytogeneticists, because it results in a considerable improvement of karyotype analysis by identifying chromosomal aberrations not previously detected by G-banding alone. Advantages, limitations, and future directions of spectral karyotyping are discussed. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Cytogenet Lab, Rochester, MN USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Labcorp, Res Triangle Pk, NC USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. Amer Med Labs, Chantilly, VA USA. Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. RP Schrock, E (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, 49 Convent Dr,Room 4C36, Bethesda, MD 20892 USA. NR 27 TC 118 Z9 120 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1997 VL 101 IS 3 BP 255 EP 262 DI 10.1007/s004390050626 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YM703 UT WOS:000071092000001 PM 9439652 ER PT J AU Silver, K Mitchell, BD Walston, J Sorkin, JD Stern, MP Roth, J Shuldiner, AR AF Silver, K Mitchell, BD Walston, J Sorkin, JD Stern, MP Roth, J Shuldiner, AR TI TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans SO HUMAN GENETICS LA English DT Article ID DEPENDENT DIABETES-MELLITUS; JAPANESE NIDDM PATIENTS; BETA(3)-ADRENERGIC RECEPTOR; GENETIC-VARIATION; INSULIN-RESISTANCE; MUTATION; WEIGHT; POLYMORPHISM; ASSOCIATION; PHENOTYPES AB The beta 3-adrenergic receptor (beta 3AR) is expressed in visceral fat and is a regulator of resting metabolic rare, thermogenesis, and lipolysis. We genotyped 61 unrelated Mexican Americans for a variant in the beta 3AR gene (codon 64 TGG(Trp)-->CGG(Arg); TRP64ARG). The allele frequency was 0.13. The TRP64ARG variant was significantly associated with an earlier age of onset of noninsulin-dependent diabetes mellitus (41.3 +/- 4.6 years vs 55.6 +/- 2.6 years; P < 0.02) and in non-diabetics, with elevated 2-h insulin levels during an oral glucose tolerance test (810 +/- 120 pmol/l vs 384 +/- 6 pmol/l; P < 0.005). Non-diabetic subjects with the variant allele tended to have higher body mass indices (BMI), waist-to-hip ratios, and diastolic blood pressures. The study group was expanded to include 421 related subjects from 31 families in the San Antonio Family Diabetes Study. Using a measured genotype analysis approach to estimate genotype-specific means for each trait, those who were homozygous for the TRP64ARG variant had significantly higher 2-h insulin levels (P = 0.036) and trends towards higher BMI compared to the other two genotypes. We detected no associations of these traits in the TRP64ARG heterozygotes in the larger group. We conclude that the TRP64ARG beta 3AR variant is a susceptibility gene for several features of the insulin resistance syndrome in Mexican Americans. Since its effects are modest, study design (e.g., subject selection, genetic background, and statistical analyses) may influence which traits are associated with this variant and whether or not the effect is detectable in heterozygotes. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NIA, NIH, Baltimore, MD 21224 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Silver, K (reprint author), Univ Maryland, Sch Med, 725 W Lombard St,Room S-415, Baltimore, MD 21201 USA. FU NIA NIH HHS [5T32AG00120]; NIDDK NIH HHS [1F32DK09340-01, R01DK49692-03] NR 38 TC 37 Z9 39 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1997 VL 101 IS 3 BP 306 EP 311 DI 10.1007/s004390050633 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YM703 UT WOS:000071092000008 PM 9439659 ER PT J AU Debelenko, LV Brambilla, E Agarwal, SK Swalwell, JI Kester, MB Lubensky, IA Zhuang, ZP Guru, SC Manickam, P Olufemi, SE Chandrasekharappa, SC Crabtree, JS Kim, YS Heppner, C Burns, AL Spiegel, AM Marx, SJ Liotta, LA Collins, FS Travis, WD EmmertBuck, MR AF Debelenko, LV Brambilla, E Agarwal, SK Swalwell, JI Kester, MB Lubensky, IA Zhuang, ZP Guru, SC Manickam, P Olufemi, SE Chandrasekharappa, SC Crabtree, JS Kim, YS Heppner, C Burns, AL Spiegel, AM Marx, SJ Liotta, LA Collins, FS Travis, WD EmmertBuck, MR TI Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung SO HUMAN MOLECULAR GENETICS LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; NEUROENDOCRINE TUMORS; RETINOBLASTOMA GENE; PARATHYROID TUMORS; P53 GENE; CHROMOSOME-11; EXPRESSION; CANCER; HETEROZYGOSITY; PROTEIN AB Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation, The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors. C1 NATL CANC INST, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIDDK, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NATL HUMAN GENOME RES INST, LAB GENE TRANSFER, NIH, BETHESDA, MD 20892 USA. UNIV GRENOBLE, CTR HOSP REG,INSERM 9701,GRP RECH CANC BRONCH CJF, LAB PATHOL CELLULAIRE, F-38043 GRENOBLE 09, FRANCE. ARMED FORCES INST PATHOL, DEPT PULM & MEDIASTINAL PATHOL, WASHINGTON, DC 20306 USA. RI Brambilla, Elisabeth/L-8796-2013; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 38 TC 172 Z9 175 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1997 VL 6 IS 13 BP 2285 EP 2290 DI 10.1093/hmg/6.13.2285 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA YJ829 UT WOS:A1997YJ82900014 PM 9361035 ER PT J AU Baird, DD Wilcox, AJ Weinberg, CR Kamel, F McConnaughey, DR Musey, PI Collins, DC AF Baird, DD Wilcox, AJ Weinberg, CR Kamel, F McConnaughey, DR Musey, PI Collins, DC TI Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women SO HUMAN REPRODUCTION LA English DT Article DE fertility; oestrogen; progesterone; unassisted conception ID LUTEAL-PHASE DEFECT; URINARY ESTROGEN; PROGESTERONE METABOLITES; ENDOMETRIAL RECEPTIVITY; PREGNANCY; IMPLANTATION; ESTRADIOL; OVULATION; RADIOIMMUNOASSAY; INTERCOURSE AB We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women, Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant, They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non-conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Stat & Biomath Branch, Res Triangle Pk, NC 27709 USA. Westat Corp, Res Triangle Pk, NC 27709 USA. Clark Atlanta Univ, Dept Biol, Atlanta, GA 30314 USA. Vet Adm Med Ctr, Decatur, GA 30329 USA. Emory Univ, Sch Med, Decatur, GA 30329 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Kamel, Freya/0000-0001-5052-6615; Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 37 TC 55 Z9 56 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 1997 VL 12 IS 12 BP 2607 EP 2613 DI 10.1093/humrep/12.12.2607 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZD605 UT WOS:000072703300009 PM 9455822 ER PT J AU Evans, GA Farrar, WL AF Evans, GA Farrar, WL TI Purification of the renaturable protein kinase PK55 by preparative isoelectric focusing and high performance electrophoretic chromatography and the generation of PK55 monoclonal antibodies by in vitro B cell stimulation SO HYBRIDOMA LA English DT Article ID RECEPTOR; ACTIVATION; GROWTH; CYCLE; CDC2 AB The analysis of T-cell activation and proliferation previously identified a renaturable protein kinase activity of 55-60 kDa (PK55) that was associated with growth arrest in T cells and other differentiated immune cell types. For further studies of this protein a rapid purification procedure was developed using preparative isoelectric focusing (IEF) and High Performance Electrophoretic Chromatography (HPEC). Near homogeneous purification of PK55 was attained using this two-step approach. Purified PK55 was used for the production of monoclonal antibodies via in vitro antigen presentation to murine splenocytes. The result of this approach yielded a single hybridoma (3B1) with high reactivity toward PK55 by ELISA. Monoclonal antibody 3B1 recognized denatured PK55 on ELISA as well as immunoblot but failed to react with the native protein. Analysis of 3B1 immunoblots of untreated or 72-h PHA-cultured T cells shows reactivity with a single 55-60 kDa (PK55) protein in untreated cells and additional reactivity to a 45 kDa protein as well as PK55 in PHA treated cells. Further analysis using monoclonal 3B1 reveals that PK55 activity is regulated by a mechanism that is distinct from changes in PK55 expression. C1 NCI, Cytokine Mol Mech Sect, Lab Mol Immunoregulat, Frederick Canc Res & Dev Ctr,IRSP, Frederick, MD 21702 USA. RP NCI, Cytokine Mol Mech Sect, Lab Mol Immunoregulat, Frederick Canc Res & Dev Ctr,IRSP, Frederick, MD 21702 USA. NR 15 TC 2 Z9 2 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1554-0014 EI 1557-8348 J9 HYBRIDOMA JI Hybridoma PD DEC PY 1997 VL 16 IS 6 BP 497 EP 502 DI 10.1089/hyb.1997.16.497 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YQ105 UT WOS:000071349000001 PM 9455701 ER PT J AU Sieckmann, DG Martin, E Guelde, G Longo, DL Kenny, JJ AF Sieckmann, DG Martin, E Guelde, G Longo, DL Kenny, JJ TI Anti-idiotype monoclonal antibodies specific for the MOPC167 anti-phosphocholine transgene-encoded antibody SO HYBRIDOMA LA English DT Article ID SOMATIC MUTATION; PHOSPHORYLCHOLINE ANTIBODIES; CELL-LINE; B-CELLS; IMMUNOGLOBULIN; DIVERSITY; BINDING; HEAVY; MICE; STIMULATION AB Four rat X mouse hybridomas secreting monoclonal anti-idiotypic (anti-Id) antibodies (MAb) specific for the transgene-encoded antibody of the 207-4 transgenic mouse line, which carries the V(H)1/V(K)24 gene segments of the IgA, phosphocholine-(PC) specific MOPC167 myeloma, were developed from a fusion of Ag8-X63.653 mouse cells with spleen cells from a rat immunized with MOPC167 and HPCM27 anti-PC antibodies. The anti-Id MAb were shown by ELISA to be specific for PC-binding proteins of V(H)1/V(K)24 and L chains of various isotypes. They did not bind V(H)1/V(K)22, V(H)1/V(K)8, or V(H)1/V(K)1 PC-binding proteins or other IgA or IgM myeloma proteins. Analysis by flow cytometry demonstrated that these MAb bind to the transgene-encoded membrane immunoglobulin (sIgM) as expressed on >95% of the B220 positive 207-4 spleen cells. All four MAb were able to inhibit the binding of MOPC167 to PC conjugated to bovine serum albumin. Differences in fine .pecificity of binding were demonstrated by differential staining of spleen cells of the 216-7 mu kappa Delta Mem MOPC167 transgenic mice. In these mice endogenous H chains associate with the transgene encoded L chain to form MOPC167 crossreactive idiotopes. Two of the MAb, 28-4-3 and 28-6-20, stained significant numbers of cells, while MAb 28-5-15 did not bind to 216-7 cells. Three of the MAb, 28-5-15, 28-6-20, and 28-4-3, when conjugated to Sepharose beads, were able to induce DNA synthesis in cultures of 207-4 transgenic spleen cells. None of the MAb were able to induce an antibody response in vivo. These MAb should prove useful in staining PC-transgenic B cells for flow cytometry studies and in defining early cellular events in the activation of idiotype positive B cells by anti-Id antibodies. C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20889 USA. USN, Med Res Inst, Bethesda, MD 20889 USA. RP Kenny, JJ (reprint author), NIA, NIH, Gerontol Res Ctr, Rm 4C19,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD DEC PY 1997 VL 16 IS 6 BP 503 EP 511 DI 10.1089/hyb.1997.16.503 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YQ105 UT WOS:000071349000002 PM 9455702 ER PT J AU Kenny, JJ AF Kenny, JJ TI 28-2-7, 28-4-3, and 28-6-20 anti-M167 idiotype or anti-V(K)24 SO HYBRIDOMA LA English DT Article C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kenny, JJ (reprint author), NIA, Gerontol Res Ctr, NIH, Rm 4C19,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD DEC PY 1997 VL 16 IS 6 BP 571 EP 571 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YQ105 UT WOS:000071349000019 ER PT J AU Kenny, JJ AF Kenny, JJ TI 28-5-15 anti-M167 idiotype or anti-V(H)1/V(k)24 SO HYBRIDOMA LA English DT Article C1 NIA, Gerontol Res Ctr, NIA, Baltimore, MD 21224 USA. RP Kenny, JJ (reprint author), NIA, Gerontol Res Ctr, NIA, Rm 4C19,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD DEC PY 1997 VL 16 IS 6 BP 572 EP 572 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YQ105 UT WOS:000071349000020 ER PT J AU Brooks, WW Bing, OHL Conrad, CH O'Neill, L Crow, MT Lakatta, EG Dostal, DE Baker, KM Boluyt, MO AF Brooks, WW Bing, OHL Conrad, CH O'Neill, L Crow, MT Lakatta, EG Dostal, DE Baker, KM Boluyt, MO TI Captopril modifies gene expression in hypertrophied and failing hearts of aged spontaneously hypertensive rats SO HYPERTENSION LA English DT Article DE angiotensin-converting enzyme inhibition; transforming growth factor-beta(1); myosin heavy chain; myocardial hypertrophy and failure ID ANGIOTENSIN-CONVERTING ENZYME; LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; MESSENGER-RNA; INTRACELLULAR CALCIUM; CARDIAC-HYPERTROPHY; AORTIC-STENOSIS; FAILURE; INHIBITION; TRANSITION AB The spontaneously hypertensive rat (SHR) exhibits a transition from stable compensated left ventricular (LV) hypertrophy to heart failure (HF) at a mean age of 21 months that is characterized by a decrease in alpha-myosin heavy chain (alpha-MHC) gene expression and increases in the expression of the atrial natriuretic factor (ANF), pro-alpha(1)(III) collagen, and transforming growth factor beta(1) (TGF-beta(1)) genes. We tested the hypotheses that angiotensin-converting enzyme inhibition (ACEI) in SHR would prevent and reverse HF-associated changes in gene expression when administered prior to and after the onset of HF, respectively. We also investigated the effect of ACEI on circulating and cardiac components of the renin-angiotensin system. ACEI (captopril 2 g/L in the drinking water) was initiated at 12, 18, and 21 months of age in SHR without HF and in SHR with HF. Results were compared with those of age-matched normortensive Wistar-Kyoto (WKY) rats, and to untreated SHR with and without evidence of HF. ACEI initiated prior to failure prevented the changes in alpha-MHC, ANF, pro-alpha(1)(III) collagen, and TGF-beta(1) gene expression that are associated with the transition to HF. ACEI initiated after the onset of HF lowered levels of TGF-beta(1) mRNA by 50% (P<.05) and elevated levels of alpha-MHC mRNA two- to threefold (P<.05). Circulating levels of renin and angiotensin I were elevated four-to sixfold by ACEI, but surprisingly, plasma levels of angiotensin II were not reduced. ACEI increased LV renin mRNA levels in WKY and SHR by two- to threefold but did not influence LV levels of angiotensinogen mRNA. The results suggest that the anti-HF benefits of ACEI in SHR may be mediated, at least in part, by effects on the expression of specific genes, including those encoding alpha-MHC, ANF, TGF-beta(1), pro-alpha(1)(III) collagen, and renin-angiotensin system components. C1 Dept Vet Affairs Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Brooks, WW (reprint author), Boston VA Med Ctr, Res Serv 151, 150 S Huntington Ave, Boston, MA 02130 USA. FU NHLBI NIH HHS [HL-44883] NR 53 TC 34 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 1997 VL 30 IS 6 BP 1362 EP 1368 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YN209 UT WOS:000071144000010 PM 9403554 ER PT J AU Sastry, S Carson, RE AF Sastry, S Carson, RE TI Multimodality Bayesian algorithm for image reconstruction in positron emission tomography: A tissue composition model SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE image reconstruction; maximum a posteriori estimation; positron emission tomography; tissue composition model ID EM ALGORITHM; GIBBS PRIORS; MAXIMUM; INFORMATION; MRI; DISTRIBUTIONS; QUANTITATION; REGISTRATION; RESTORATION; BRAIN AB The use of anatomical information to improve the quality of reconstructed images in positron emission tomography (PET) has been extensively studied, A common strategy has been to include spatial smoothing within boundaries defined from the anatomical data, We present an alternative method for the incorporation of anatomical information into PET image reconstruction, in which we use segmented magnetic resonance (MR) images to assign tissue composition to PET image pixels. We model the image as a sum of activities for each tissue type, weighted by the assigned tissue composition, The reconstruction is performed as a maximum a posteriori (MAP) estimation of the activities of each tissue type, Two prior functions, defined for tissue-type activities, are considered, The algorithm is tested in realistic simulations employing a full physical model of the PET scanner. C1 NIH, Positron Emiss Tomog Dept, Ctr Clin, Phys Sci Lab,Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, Positron Emiss Tomog Dept, Ctr Clin, Phys Sci Lab,Div Comp Res & Technol, Bethesda, MD 20892 USA. EM richard-e-carson@nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 33 TC 45 Z9 45 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 1997 VL 16 IS 6 BP 750 EP 761 DI 10.1109/42.650872 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZB313 UT WOS:000072458500006 PM 9533576 ER PT J AU Daube-Witherspoon, ME Carson, RE AF Daube-Witherspoon, ME Carson, RE TI Investigation of angular smoothing of PET data SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) CY NOV 05-09, 1996 CL ANAHEIM, CALIFORNIA SP Inst Elect & Electr Engineers ID POSITRON EMISSION TOMOGRAPHY; ATTENUATION CORRECTION; TRANSMISSION; SCANS AB Radial filtering of emission and transmission data is routinely performed in PET during reconstruction in order to reduce image noise. Angular smoothing is not typically done, due to the introduction of a non-uniform resolution loss. The goal of this paper was to assess the effects of angular smoothing on noise and resolution. Angular smoothing was incorporated into the reconstruction process on the Scanditronix PC2048-15B brain PET scanner. In-plane spatial resolution and noise reduction were measured for different amounts of radial and angular smoothing. For radial positions away from the center of the scanner, noise reduction and degraded tangential resolution with negligible loss of radial resolution were seen. Near the center, no resolution loss was observed, but there was also no reduction in noise even for large amounts of angular filtering. These results can be understood by recognizing that angular filtering is equivalent to a weighted sum of rotated images. We conclude that angular smoothing is not optimal due to its anisotropic noise reduction and resolution degradation properties. C1 NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Daube-Witherspoon, ME (reprint author), NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bldg 10-1C497, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 10 TC 8 Z9 8 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD DEC PY 1997 VL 44 IS 6 BP 2494 EP 2499 DI 10.1109/23.656458 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA YM433 UT WOS:000071063000018 ER PT J AU Hodes, RJ AF Hodes, RJ TI Aging and the immune system SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material C1 NCI, Natl Inst Aging & Expt, Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NCI, Natl Inst Aging & Expt, Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 16 TC 60 Z9 60 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1997 VL 160 BP 5 EP 8 DI 10.1111/j.1600-065X.1997.tb01022.x PG 4 WC Immunology SC Immunology GA YQ130 UT WOS:000071351500001 PM 9476660 ER PT J AU Weng, NP Palmer, LD Levine, BL Lane, HC June, CH Hodes, RJ AF Weng, NP Palmer, LD Levine, BL Lane, HC June, CH Hodes, RJ TI Tales of tails: Regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation, and aging SO IMMUNOLOGICAL REVIEWS LA English DT Review ID IMMORTAL CELL-LINES; CENTER B-CELLS; T-CELLS; HEMATOPOIETIC-CELLS; HUMAN FIBROBLASTS; SOMATIC MUTATION; MEMORY-B; INFECTION; DNA; AGE AB Telomerase activity and the regulation of telomere length are factors which have been implicated in the control of cellular replication. These variables have been examined during human lymphocyte development, differentiation, activation, and aging. It was found that telomere length of peripheral blood CD4(+) T cells decreases with age as well as with differentiation from naive to memory cells in vivo, and decreases with cell division in vitro. These results provide evidence that telomere length correlates with lymphocyte replicative history and residual replicative potential. In contrast, telomere length appears to increase during tonsil B-cell differentiation and germinal center (GC) formation in vivo. It was also found that telomerase activity is highly regulated during T-cell development and B-cell differentiation in vivo, with high levels of telomerase activity expressed in thymocytes and GC B cells, and low levels of telomerase activity in resting mature peripheral blood lymphocytes. Finally, resting lymphocytes retain the ability to upregulate telomerase activity upon activation, and this capacity does not appear to decline with age. Although the precise role of telomerase in lymphocyte function remains to be elucidated, telomerase may contribute to protection from telomere shortening in T and B lymphocytes, and may thus play a critical role in lymphocyte development, differentiation and activation. The future study of telomerase and its regulation of telomere length may enhance our understanding of how the replicative lifespan is regulated in lymphocytes. C1 NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US Mil HIV Res Program, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, RM 4C16 Box 21,4940 Eastern Ave, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov RI Levine, Bruce/D-1688-2009 NR 88 TC 149 Z9 155 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1997 VL 160 BP 43 EP 54 DI 10.1111/j.1600-065X.1997.tb01026.x PG 12 WC Immunology SC Immunology GA YQ130 UT WOS:000071351500005 PM 9476664 ER PT J AU Mackall, CL Gress, RE AF Mackall, CL Gress, RE TI Thymic aging and T-cell regeneration SO IMMUNOLOGICAL REVIEWS LA English DT Review ID BONE-MARROW TRANSPLANTATION; OLD MICE; INTENSIVE CHEMOTHERAPY; MITOTIC RESPONSIVENESS; RHEUMATOID-ARTHRITIS; EPITHELIAL-CELLS; LYMPHOCYTES-T; AGE; DIFFERENTIATION; GONADECTOMY AB Studies of T-cell regeneration using animal models have consistently shown the importance of the thymus for T-cell regeneration. In humans, recent studies have shown that declines in thymic T-cell regenerative capacity begins relatively early in life, resulting in a limited capacity for T-cell regeneration by young adulthood. As a result, adult humans who experience profound T-cell depletion regenerate T cells primarily via relatively inefficient thymic-independent pathways, resulting in prolonged CD4 depletion, CD4(+) and CD8(+) subset alterations, limited TCR repertoire diversity and a propensity for activation induced cell death. These limitations in T-cell regeneration have significant clinical implications in the setting of HIV infection and bone marrow transplantation and may also contribute to immunologic abnormalities associated with normal aging. While the mechanisms responsible for thymic aging are not well understood, current evidence suggests that changes within the thymus itself are primary, while age-related changes in marrow T-cell progenitors and inhibitory factors within the extrathymic host milieu contribute to a lesser extent. The development of therapies which can reverse thymic aging are critical for improving outcome in clinical settings of T-cell depletion, and could potentially improve immunologic function in normal aged hosts. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol & Med Branch, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr MSC 1928, Bethesda, MD 20892 USA. NR 69 TC 183 Z9 186 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1997 VL 160 BP 91 EP 102 DI 10.1111/j.1600-065X.1997.tb01030.x PG 12 WC Immunology SC Immunology GA YQ130 UT WOS:000071351500009 PM 9476668 ER PT J AU Vliagoftis, H Metcalfe, DD AF Vliagoftis, H Metcalfe, DD TI Characterization of adhesive interactions between mast cells and laminin isoforms: evidence of a principal role for alpha 6 integrin SO IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; A-CHAIN; FIBRONECTIN; ATTACHMENT; EXPRESSION; RECEPTOR; BINDING; PHOSPHORYLATION; IDENTIFICATION; ALPHA-5-BETA-1 AB Mast cells are known to adhere to laminin, although there is limited information on the characteristics of this event. To further examine this adhesive interaction, we thus determined the adherence of murine mast cell lines and primary bone marrow cultured mast cells (BMCMC) to murine laminin (mLN), human placental laminin-1 (hLN), merosin (laminin-2) and various laminin fragments, concentrating on activating stimuli, the involvement of integrins, and the effect on mast cell activation. Murine mast cells were found to adhere to both mLN and hLN and to merosin, not only following exposure to phorbol 12-myristate 13-acetate (PMA), but also after Fc epsilon RI aggregation or addition of stem cell factor (SCF). Adhesion to laminin was partially inhibited by soluble E8 and PA22-2, both fragments of laminin that promote mast-cell adhesion when bound on surfaces. Mast-cell Lines and BMCMC consistently expressed high levels of alpha 6 integrin. Antibody to alpha 6 blocked spontaneous and inhibited activated mast-cell adhesion to hLN, and inhibited mast-cell adhesion to mLN and its fragment E8. Mast-cell adhesion to both laminin isoforms increased Fc epsilon RI-mediated mast-cell secretion. These observations demonstrate that mast-cell attachment to laminin is promoted by physiological stimuli, is mediated principally by alpha 6 integrin, and results in enhanced cell activation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Vliagoftis, H (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. RI Vliagoftis, Harissios/C-6480-2013 NR 32 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1997 VL 92 IS 4 BP 553 EP 560 DI 10.1046/j.1365-2567.1997.00368.x PG 8 WC Immunology SC Immunology GA YL823 UT WOS:000070997400018 PM 9497498 ER PT J AU Shaw, S Turni, L Katz, K AF Shaw, S Turni, L Katz, K TI Protein reviews on the Web controlling flood of biological information SO IMMUNOLOGY TODAY LA English DT Article RP Shaw, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 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 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD DEC PY 1997 VL 18 IS 12 BP 557 EP 558 DI 10.1016/S0167-5699(97)01177-8 PG 2 WC Immunology SC Immunology GA YL038 UT WOS:A1997YL03800001 ER PT J AU Solomon, SD AF Solomon, SD TI Psychosocial treatment of posttraumatic stress disorder SO IN SESSION-PSYCHOTHERAPY IN PRACTICE LA English DT Article DE posttraumatic stress disorder (PTSD); traumatic stress; treatment; psychotherapy; psychosocial treatment AB A review of the psychosocial treatment research literature indicates that several forms of therapy appear to be useful in reducing the symptoms of posttraumatic stress disorder (PTSD). Strongest support is found for the treatments that combine cognitive and behavioral techniques. Hypnosis, psychodynamic, anxiety management and group therapies may also produce short-term symptom reduction. Still unknown is whether any approach produces lasting effects. Imaginal exposure to trauma memories and hypnosis are techniques most likely to affect the intrusive symptoms of PTSD, whereas cognitive and psychodynamic approaches may better address the numbing and avoidance symptom cluster: Treatment should be tailored to tbe severity and type of presenting PTSD symptoms, to the type of trauma experience, and to the many likely comorbid diagnoses and adjustment problems. (C) 1997 John Wiley & Sons, Inc. C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Solomon, SD (reprint author), NIH, Off Behav & Social Sci Res, Fed Bldg,Room 8C-16,7550 Wisconsin Ave, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 6 U1 4 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1077-2413 J9 IN SESSION-PSYCHOTH JI In Session-Psychother. Pract. PD WIN PY 1997 VL 3 IS 4 BP 27 EP 41 PG 15 WC Psychology, Clinical SC Psychology GA YN949 UT WOS:000071225000004 ER PT J AU Petter, R Chang, YC KwonChung, KJ AF Petter, R Chang, YC KwonChung, KJ TI A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASE; INTACT YEAST-CELLS; GLUCOSE REPRESSION; SUCROSE UTILIZATION; CARBON METABOLISM; TRANSFORMATION; EXPRESSION; DISRUPTION; VIRULENCE; CLONING AB The SNF1 gene of Saccharomyces cerevisiae (ScSNF1) is essential for the derepression of catabolic repression. We report here the isolation and characterization of an SNF1 homolog from Candida albicans (CaSNF1) which is apparently essential for the viability of this organism. The putative amino acid sequence of CaSNF1 has 68% identity with that of ScSNF1 and can restore the S. cerevisiae snf1 Delta mutant's ability to utilize sucrose. Disruption of one of the CaSNF1 alleles resulted in morphological changes and decreased growth rates but did not modify the carbon source utilization pattern. Repetitive unsuccessful attempts to generate a snf1/snf1 homozygote by disruption of the second allele, using various vectors and approaches, suggest the lethal nature of this mutation. Integration into the second allele was possible only when a full-length functional SNF1 sequence was reassembled, further supporting this hypothesis and indicating that the indispensability of Snf1p prevented the isolation of snf1/snf1 mutants. The mutant bearing two disrupted SNF1 alleles and the SNF1 functional sequence maintained its ability to utilize sucrose and produced stellate colonies with extensive hyphal growth on agar media. It was demonstrated that in a mouse model, the virulences of this mutant and the wild-type strain are similar, suggesting that hyphal growth in vitro is not an indicator for higher virulence. C1 NIAID, MIL MICROBIOL SECT, LCI, NIH, BETHESDA, MD 20892 USA. NR 40 TC 29 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1997 VL 65 IS 12 BP 4909 EP 4917 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YJ227 UT WOS:A1997YJ22700003 PM 9393775 ER PT J AU vanPutten, JPM Hayes, SF Duensing, TD AF vanPutten, JPM Hayes, SF Duensing, TD TI Natural proteoglycan receptor analogs determine the dynamics of Opa adhesin-mediated gonococcal infection of Chang epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID NEISSERIA-GONORRHOEAE; SALMONELLA-TYPHIMURIUM; PHASE VARIATION; PROTEIN-II; OPACITY PROTEINS; HEPARAN-SULFATE; INVASION; POLYSACCHARIDES; MENINGITIDIS; CYTOSKELETON AB Many bacterial pathogens possess a complex machinery for the induction and/or secretion of factors that promote their uptake by mammalian cells. We searched for the molecular basis of the 60- to 90-min lag time in the interaction of Neisseria gonorrhoeae carrying the heparin-binding Opa adhesin with Chang epithelial cells. Infection assays in the presence of chloramphenicol demonstrated that the Opa-mediated gonococcal infection of Chang cells required bacterial protein synthesis when the microorganisms were derived from GC agar but not when grown in liquid media. Further analysis indicated that contact with agar ingredients rather than the growth state of the microorganisms determined the infection dynamics. DEAE chromatography of GC agar extracts and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses and testing of collected fractions in infection assays identified negatively charged high-molecular-weight polysaccharides in the agar as inhibitors of the cellular infection. Electron microscopy showed that agar-grown gonococci were surrounded by a coat of alcian blue-positive material, probably representing accreted polysaccharides. Similar antiphagocytic material was isolated from bovine serum, indicating that in biological fluids gonococci producing the heparin-binding Opa adhesin may become covered with externally derived polysaccharides as well. Binding assays with gonococci and epithelial proteoglycan receptors revealed that polysaccharides derived from agar or serum compete with the proteoglycans for binding of the heparin-binding Opa adhesin and thus act as receptor analogs. Growth of gonococci in a polysaccharide-free environment resulted in optimal proteoglycan receptor binding and rapid bacterial entry into Chang cells. The recognition that gonococci with certain phenotypes can recruit surface polysaccharides that determine in vitro infection dynamics adds a different dimension to the well-recognized biological significance of genetic variation for this pathogen. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,NIH,HAMILTON,MT 59840. RP vanPutten, JPM (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. OI van Putten, Jos/0000-0002-4126-8172 NR 47 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1997 VL 65 IS 12 BP 5028 EP 5034 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YJ227 UT WOS:A1997YJ22700020 PM 9393792 ER PT J AU Cisar, JO Sandberg, AL Reddy, GP Abeygunawardana, C Bush, CA AF Cisar, JO Sandberg, AL Reddy, GP Abeygunawardana, C Bush, CA TI Structural and antigenic types of cell wall polysaccharides from viridans group streptococci with receptors for oral actinomyces and streptococcal lectins SO INFECTION AND IMMUNITY LA English DT Article ID SANGUIS ATCC 10557; VISCOSUS T14V; SURFACE POLYSACCHARIDE; NAESLUNDII WVU45; MITIS J22; COAGGREGATION; BINDING; BACTERIA; STREPTOCOCCUS-SANGUIS-34; GLYCOSPHINGOLIPIDS AB Lectin-mediated interactions between oral viridans group streptococci and actinomyces may play an important role in microbial colonization of the tooth surface. The presence of two host-like motifs, either GalNAc beta 1-->3Gal (Gn) or Gal beta 1-->3GalNAc (G), in the cell wall polysaccharides of five streptococcal strains accounts for the lactose-sensitive coaggregations of these bacteria with Actinomyces naeslundii. Three streptococcal strains which have Gn-containing polysaccharides also participate in GalNAc-sensitive coaggregations with strains of Streptococcus gordonii and S. sanguis, Each Gn-or G-containing polysaccharide is composed of a distinct phosphodiester-linked hexa-or heptasaccharide repeating unit. The occurrence of these polysaccharides on 19 additional viridans group streptococcal strains that participate in lactose-sensitive coaggregations with actinomyces was examined, Negatively charged polysaccharides that reacted with Bauhinia purpurea agglutinin, a Gal and GalNAc binding plant lectin, were isolated from 17 strains by anion exchange column chromatography of mutanolysin-cell wall digests. Results from nuclear magnetic resonance and immunodiffusion identified each of 16 polysaccharides as a known Gn-or G-containing structural type and one polysaccharide as a new but closely related Gn-containing type. Unlike the reactions of lectins, the cross-reactions of most rabbit antisera with these polysaccharides were correlated with structural features other than the host-like motifs. Gn-containing polysaccharides occurred primarily on the strains of S. sanguis and S. oralis while G-containing polysaccharides were more common among the strains of S. gordonii and S. mitis examined. The findings strongly support the hypothesis that lectin-mediated recognition of these streptococci by other oral bacteria depends on a family of antigenically diverse Gn-and G-containing cell wall polysaccharides, the occurrence of which may differ between streptococcal species. C1 UNIV MARYLAND BALTIMORE CTY,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. RP Cisar, JO (reprint author), NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BLDG 30,ROOM 302,BETHESDA,MD 20892, USA. NR 45 TC 54 Z9 56 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1997 VL 65 IS 12 BP 5035 EP 5041 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YJ227 UT WOS:A1997YJ22700021 PM 9393793 ER PT J AU Takahashi, Y Sandberg, AL Ruhl, S Muller, J Cisar, JO AF Takahashi, Y Sandberg, AL Ruhl, S Muller, J Cisar, JO TI A specific cell surface antigen of Streptococcus gordonii is associated with bacterial hemagglutination and adhesion to alpha 2-3-linked sialic acid-containing receptors SO INFECTION AND IMMUNITY LA English DT Article ID SALIVA-COATED HYDROXYAPATITE; ACTINOMYCES-VISCOSUS T14V; MONOCLONAL-ANTIBODIES; MEDIATED AGGREGATION; BINDING PROTEIN; SANGUIS C5; GLYCOPROTEIN; FIMBRIAE; CLONING; ACTINOMYCES-VISCOSUS-T14V AB A Ca2+-independent Lectin activity for alpha 2-3-linked sialic acid-containing receptors is associated with Streptococcus gordonii DL1 (Challis) but not with a spontaneous mutant, strain D102, that specifically Larks hemagglutinating activity, Comparison of crossed-immunoelectrophoresis patterns of parent and mutant sonicated cell extracts identified a unique antigen (Hs antigen) in the parent cell extract that was purified by DEAE Sephacel column chromatography and by a wheat germ agglutinin (WGA) lectin affinity column. The purified antigen formed a single are in crossed immunoelectrophoresis with anti-DL1 serum and migrated as a diffuse band above the 200-kDa marker in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Immunoelectron microscopy with specific anti-Ils antibody revealed labeling of structures in the fibrillar layer of strain DL1 and no labeling of fibrillar structures on strain D102, Rabbit anti-DL1 serum and anti-Hs Fab inhibited the hemagglutinating activity of strain DL1, and the inhibition was specifically neutralized by purified Hs antigen, Anti-Hs Fab did not inhibit the hemagglutinating activities of several heterologous S. gordonii strains; however, these bacteria were agglutinated by anti-as immunoglobulin G and also by WGA. In contrast, two S. gordonii strains that lacked hemagglutinating activity did not react with anti-as antibody or with WGA, These findings associate the sialic acid-binding lectin activity of S. gordonii DL1 with a specific fibrillar antigen, which is composed of protein and WGA reactive carbohydrate, and indicate that crossreactive antigens occur on other strains of this species that possess hemagglutinating activity. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROC,ROCKVILLE,MD 20852. NR 48 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1997 VL 65 IS 12 BP 5042 EP 5051 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YJ227 UT WOS:A1997YJ22700022 PM 9393794 ER PT J AU Sunderland, T Lasser, RA Levin, R Dukoff, RA AF Sunderland, T Lasser, RA Levin, R Dukoff, RA TI Depression in the elderly: biologic considerations SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Lundbeck Symposium on Affective Disorders and Other Emotional Disturbances in the Elderly, at the 6th World Congress of Biological Psychiatry CY JUN 26, 1997 CL NICE, FRANCE DE geriatric depression; biologic markers; late-onset depression; apolipoprotein E ID ALZHEIMERS-DISEASE; LATE-ONSET; GERIATRIC DEPRESSION; COGNITIVE IMPAIRMENT; MAJOR DEPRESSION; SENILE DEMENTIA; RISK-FACTORS; AGE; ANTIDEPRESSANTS; ALLELE AB Although support for the biologic basis and effective somatic therapy of geriatric depression is increasing, both patients and clinicians are reluctant to identify and treat the symptoms associated with late-life depression, a broad-based problem in the geriatric population. There is much clinical and biologic overlap between depression and other organic brain disorders such as dementia, with evidence that late-onset depression may sometimes be a prodrome for other organic disorders. These and other issues surrounding geriatric depression are reviewed with a focus on future research questions. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Bldg 10,Room 3N-228,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD DEC PY 1997 VL 12 SU 7 BP S15 EP S18 DI 10.1097/00004850-199712007-00003 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YW327 UT WOS:000071922800003 PM 9476135 ER PT J AU Wessels, H Lamb, ME Hwang, CP Broberg, AG AF Wessels, H Lamb, ME Hwang, CP Broberg, AG TI Personality development between 1 and 8 years of age in Swedish children with varying child care experiences SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID SOCIAL-DEVELOPMENT; PRESCHOOLERS; QUALITY; DETERMINANTS; TEMPERAMENT; COMPETENCE; INFANCY; FAMILY AB In this longitudinal study, 122 Swedish children were followed from an initial assessment at 16 months until they were 8.5 years of age. Parental ratings of field independence, ego-resilience, and ego-control were obtained using the California Child Q-set when the children averaged 28, 40, 80, and 101 months of age. These assessments of personality were then examined in the context of contrasting child care experiences. There was virtually no difference between the developmental trajectories of the children in home care and in centre-based day care. In contrast, ego-undercontrol decreased less, whereas ego-resilience and field independence increased less, in children who attended family day care than in the children in either centre care or exclusive parental care. The quality of home and out-of-home care, as well as socioeconomic status and family background, did not moderate or qualify these effects of the type of care experienced. The results are discussed in relation to previous work on the effects of early out-of-home care on child development. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20814 USA. Gothenburg Univ, S-41124 Gothenburg, Sweden. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. NR 42 TC 6 Z9 6 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD DEC PY 1997 VL 21 IS 4 BP 771 EP 794 PG 24 WC Psychology, Developmental SC Psychology GA YR920 UT WOS:000071545100008 ER PT J AU Wolffe, AP AF Wolffe, AP TI Histone H1 SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE nucleosome; chromatin; transcriptional control; translational control; developmental control ID CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; LINKER HISTONES; BINDING-SITE; NUCLEOSOME; CHROMATIN; DNA; H-1 AB Linker histones of which histone H1 is a representative are a diverse family of architectural proteins within the eukaryotic nucleus. These proteins have a variety of structures, but invariably contain a region enriched in lysine, serine, alanine and proline. All metazoan histone His also include a structured domain that binds to DNA through a helix-turn-helix motif. By binding to the linker DNA flanking the nucleosome core they contribute to the assembly of higher-order chromatin structures. Surprisingly, the use of "knockout" technology to eliminate histone H1 in isolated cells and Xenopus does not prevent the assembly of chromosomes or nuclei, however specific genes are activated or repressed indicative of targeted regulatory functions. A dual role for histone H1 in chromatin structure and gene regulation might contribute to epigenetic phenomena in,which heritable states of gene activity are maintained through mechanisms independent of gene sequence. This may have important implications for biotechnological and medical research. (C) 1997 Elsevier Science Ltd. All rights reserved. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 13 TC 55 Z9 56 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD DEC PY 1997 VL 29 IS 12 BP 1463 EP 1466 DI 10.1016/S1357-2725(97)00026-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG429 UT WOS:000073001300012 PM 9570139 ER PT J AU Tomarev, SI AF Tomarev, SI TI Pax-6, Eyes absent, and Prox 1 in eye development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE eye; evolution; Pax-6; Prox 1; Eya 2; prospero; eyeless; eyes absent ID DROSOPHILA VISUAL-SYSTEM; HOMEOBOX GENE PROX-1; TRANSCRIPTION FACTOR; SINE OCULIS; ASYMMETRIC SEGREGATION; CUBITUS-INTERRUPTUS; PROSPERO GENE; EYELESS GENE; NEURAL PLATE; CELL FATES AB Eyes in different systematic groups including arthropods, molluscs and vertebrates probably have a common evolutionary origin. As a consequence of this, related genes are used for regulation of the early steps of eye development in different organisms. In this review, I briefly summarize data on three gene families which might be essential for eye development across species: Pax-6/eyeless, Eya/eyes absent and Prox/prospero with emphasis on our contribution here. Mechanisms of eye formation and the generation of different types of eyes in the course of evolution are discussed. RP Tomarev, SI (reprint author), NEI,MOL & DEV BIOL LAB,BLDG 6,ROOM 203,6 CTR DR,MSC 2720,BETHESDA,MD 20892, USA. NR 78 TC 23 Z9 23 U1 0 U2 1 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD DEC PY 1997 VL 41 IS 6 BP 835 EP 842 PG 8 WC Developmental Biology SC Developmental Biology GA YK963 UT WOS:A1997YK96300012 PM 9449459 ER PT J AU Weed, DL AF Weed, DL TI On the use of causal criteria SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE causal inference; epidemiology; ethics; methods; philosophy of science; theory ID EPIDEMIOLOGY; CANCER; BIAS AB Background. Two recent accounts of the use of causal criteria make opposite claims: that criteria should be used more often to avoid bias in assessments of weak associations and, in direct contrast, that criteria are scientifically invalid. Methods. A recent review of the current practice of causal inference in epidemiology, as well as some more theoretical concerns, reveals errors in the two claims. Results. In practice, epidemiologists often use the criteria of consistency, strength, dose-response, and biological plausibility, but not often temporality, when judging weak associations. These criteria are used for causal assessments as well as for making public health recommendations. In theory, causal criteria can be used to either refute or predict causal effects. Conclusion. Research on causal inference methodology should be encouraged, including research on underlying theory, methodology, and additional systematic descriptions of how causal inference is practised. Specific research questions include: to what extent can consensus be achieved on definitions and accompanying rules of inference for criteria, the relationship of meta-analysis to the criterion of consistency, and the interrelationships of criteria such as consistency, strength of association, and biological plausibility. C1 NCI, Prevent Oncol Branch, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), NCI, Prevent Oncol Branch, EPS T-41,6130 Execut Blvd,MSC 7105, Bethesda, MD 20892 USA. NR 30 TC 48 Z9 50 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1997 VL 26 IS 6 BP 1137 EP 1141 DI 10.1093/ije/26.6.1137 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YP308 UT WOS:000071263900001 PM 9447391 ER PT J AU Johnson, ES Shorter, C Rider, B Jiles, R AF Johnson, ES Shorter, C Rider, B Jiles, R TI Mortality from cancer and other diseases in poultry slaughtering/processing plants SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE avian leukosis/sarcoma viruses; reticuloendotheliosis virus; Marek's disease virus; chickens; turkeys ID MEAT INDUSTRY; MULTIPLE-MYELOMA; RETICULOENDOTHELIOSIS VIRUSES; ONCOGENIC RETROVIRUSES; FARM PRACTICES; LUNG-CANCER; LEUKEMIA; HUMANS; WORKERS; HERPESVIRUS AB Background. Healthy chickens or turkeys and their eggs destined for human consumption are commonly infected with viruses which cause cancer in these animals. Some of the viruses can infect and transform human cells in vitro, and human sera show serological evidence of infection with these viruses. It is not known whether the viruses cause cancer in humans. Methods. We conducted a mortality study of a subcohort of 2639 workers in poultry slaughtering plants who have one of the highest human exposures to these viruses, and 6081 unexposed workers from non-meat companies (controls). All were members of a local meatcutters' union in Baltimore. Results. Statistically significant increased risks were observed for cancer of the oesophagus, liver cancer, tumours of the haemopoietic lymphatic system, and motor vehicle accidents, in the group of poultry workers as a whole or in particular race/ sex subgroups. The results for other causes of death showed consistently elevated risks in most race/sex subgroups, but these were not statistically significant. Conclusion. The cohort is young, and because the number of deaths is small, the results though suggestive of increased risks for some causes, are inconclusive. However they indicate that this cohort is of interest, and that further follow-up might reveal a much clearer and consistent picture. C1 Tulane Univ, Med Ctr, Sch Publ Hlth & Trop Med, Dept Biostat & Epidemiol, New Orleans, LA 70112 USA. NIEHS, Sect Environm & Mol Epidemiol, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Johnson, ES (reprint author), Tulane Univ, Med Ctr, Sch Publ Hlth & Trop Med, Dept Biostat & Epidemiol, SL18,1430 Tulane Ave, New Orleans, LA 70112 USA. FU NCI NIH HHS [R01 CA 30410] NR 44 TC 26 Z9 26 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1997 VL 26 IS 6 BP 1142 EP 1150 DI 10.1093/ije/26.6.1142 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YP308 UT WOS:000071263900002 PM 9447392 ER EF