FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Andersen, RN Ganeshkumar, N Kolenbrander, PE AF Andersen, RN Ganeshkumar, N Kolenbrander, PE TI Helicobacter pylori adheres selectively to Fusobacterium spp. SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Helicobacter-Fusobacterium coaggregation; helicobacter oral sequestration ID POLYMERASE CHAIN-REACTION; DENTAL PLAQUE; DUODENAL-ULCER; GASTRIC-CANCER; ORAL BACTERIA; COAGGREGATION; INFECTION; CAMPYLOBACTER; SALIVA; PCR AB Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Kolenbrander, PE (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr MSC 4350, Bethesda, MD 20892 USA. NR 42 TC 30 Z9 32 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1998 VL 13 IS 1 BP 51 EP 54 DI 10.1111/j.1399-302X.1998.tb00751.x PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA YU189 UT WOS:000071691200009 PM 9573823 ER PT J AU Benoliel, R Sharav, Y AF Benoliel, R Sharav, Y TI SUNCT syndrome - Case report and literature review SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Review ID NEURALGIFORM HEADACHE ATTACKS; CHRONIC PAROXYSMAL HEMICRANIA; CONJUNCTIVAL INJECTION; TRIGEMINAL NEURALGIA; PAIN; ACTIVATION; CAT AB The case of a woman with short neuralgiform paroxysmal pain of 2 years duration is described. Pain attacks were always accompanied by ipsilateral lacrimation and conjunctival injection. Standard anti-neuralgic therapy, amitriptyline and indomethacin, failed to eliminate or reduce pain. At the end of a 30-month active period the patient seemed to have gone into remission. We believe this to be a case of short-lasting. unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) the first reported in the dental literature and the 24th in the general medical literature. The differential diagnosis of the case and relevant literature are discussed. C1 Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dep Oral Diag Oral Med & Oral Radiol, Orofacial Pain Clin, IL-91010 Jerusalem, Israel. RP Benoliel, R (reprint author), NIDR, BDS, NIH, Bldg 49,Room 1WW25, Bethesda, MD 20892 USA. NR 41 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD FEB PY 1998 VL 85 IS 2 BP 158 EP 161 DI 10.1016/S1079-2104(98)90419-X PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YX101 UT WOS:000072006500009 PM 9503449 ER PT J AU Robbins, PF AF Robbins, PF TI Antigens recognized by melanoma-reactive T cells and the development of cancer immunotherapy SO PATHOLOGIE BIOLOGIE LA English DT Article; Proceedings Paper CT 2nd Joseph R Coulter Symposium on Immuno-Intervention in Cancer CY APR 01-02, 1997 CL MARSEILLE, FRANCE DE T lymphocytes; antigens; cancer immunotherapy ID LYMPHOCYTES C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Robbins, PF (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2842,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD FEB PY 1998 VL 46 IS 2 BP 138 EP 139 PG 2 WC Pathology SC Pathology GA ZD414 UT WOS:000072682800027 ER PT J AU Ward, JM Konishi, N Ohshima, M Lamb, PW Jorcyk, CL Barrett, JC AF Ward, JM Konishi, N Ohshima, M Lamb, PW Jorcyk, CL Barrett, JC TI Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines SO PATHOLOGY INTERNATIONAL LA English DT Article DE benign prostatic hyperplasia; immunohistochemistry; KAl1; prostate; prostatic intraepithelial neoplasia ID METASTASIS SUPPRESSOR GENE; SYNCYTIUM FORMATION; CANCER; ANTIBODIES; PROTEIN; MEMBER; ANTIGEN; FAMILY; CD82 AB Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by immunohistochemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. in human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. in some cases, pretreatment with trypsin enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining revels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmic localization of the protein in cells. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Nara Med Univ, Kashihara, Nara 634, Japan. Nissei Hosp, Osaka, Japan. RP Ward, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Fairview 201,POB B, Frederick, MD 21702 USA. NR 13 TC 13 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD FEB PY 1998 VL 48 IS 2 BP 87 EP 92 DI 10.1111/j.1440-1827.1998.tb03876.x PG 6 WC Pathology SC Pathology GA ZM229 UT WOS:000073517600001 PM 9589471 ER PT J AU Yasumi, K Guo, RJ Hanai, H Arai, H Kaneko, E Konno, H Takenoshita, S Hagiwara, K Sugimura, H AF Yasumi, K Guo, RJ Hanai, H Arai, H Kaneko, E Konno, H Takenoshita, S Hagiwara, K Sugimura, H TI Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype SO PATHOLOGY INTERNATIONAL LA English DT Article DE malignant lymphoma; maltoma; stomach; transforming growth factor beta type II receptor ID GENOMIC STRUCTURE; GENE; EXPRESSION; CANCERS AB A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the Clinical characteristics of the patient in this study are intriguing. C1 Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 43131, Japan. Hamamatsu Univ Sch Med, Dept Med 1, Hamamatsu, Shizuoka 43131, Japan. Hamamatsu Univ Sch Med, Dept Surg 2, Hamamatsu, Shizuoka 43131, Japan. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Sugimura, H (reprint author), Hamamatsu Univ Sch Med, Dept Pathol 1, 3600 Handa Cho, Hamamatsu, Shizuoka 43131, Japan. EM hsugimur@hama-med.ac.jp NR 17 TC 8 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD FEB PY 1998 VL 48 IS 2 BP 134 EP 137 DI 10.1111/j.1440-1827.1998.tb03882.x PG 4 WC Pathology SC Pathology GA ZM229 UT WOS:000073517600007 PM 9589477 ER PT J AU Kline, MW Van Dyke, RB Lindsey, JC Gwynne, M Culnane, M McKinney, RE Nichols, S Mitchell, WG Yogev, R Hutcheon, N AF Kline, MW Van Dyke, RB Lindsey, JC Gwynne, M Culnane, M McKinney, RE Nichols, S Mitchell, WG Yogev, R Hutcheon, N CA AIDS Clin Trials Grp 240 Team TI A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection SO PEDIATRICS LA English DT Article DE stavudine; zidovudine; HIV infection; infant or child ID ORAL ZIDOVUDINE; THERAPY; INVITRO; GROWTH; DIDANOSINE; TOLERANCE; SAFETY; POTENT; AIDS AB Objectives. To compare the safety and tolerance of stavudine (d4T) versus zidovudine (ZDV, AZT) in symptomatic human immunodeficiency virus-infected children 3 months to 6 years of age. Methods. In an initially double-blind trial, 212 evaluable human immunodeficiency virus-infected children who had received no more than 6 weeks of previous antiretroviral therapy were randomized to receive either d4T (1 mg/kg orally every 12 hours, maximum 40 mg orally every 12 hours) or zidovudine (180 mg/m(2) orally every 6 hours, maximum 200 mg orally every 6 hours). The study was unblinded after a median follow-up period of 6.3 months; median follow-up at study closure was 17.3 months. Tolerance, safety, disease progression, and immunologic responses were evaluated. Results. The patient population was young (median age, 1.2 years; range, 0.3 to 6.4 years), with a median baseline CD4+ lymphocyte count of 965 cells/mu L (range, 18 to 4238 cells/mu L). Neutropenia <400/mu L occurred significantly more commonly among zidovudine recipients (1-year event rates of 20% both up to the time of unblinding and throughout the entire study) than among children receiving d4T (1-year event rates of 5% up to the time of unblinding and 6% throughout the entire study). In exploratory activity analyses using all data collected until study closure, children treated with d4T showed consistently greater positive changes from baseline in weight-for-age-and-gender z scores. As expected in this population of young children, median absolute CD4+ lymphocyte counts decreased in both treatment groups. Smaller changes from baseline were noted among d4T recipients. Conclusions. In children between the ages of 3 months and 6 years, d4T and zidovudine are largely comparable in terms of safety and tolerance. Neutropenia occurs significantly less commonly among children treated with d4T. There was evidence that weight gain and absolute CD4+ lymphocyte counts were better maintained in children receiving d4T. C1 Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Pediat ACTG Operat Ctr, Rockville, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, San Diego, CA 92103 USA. Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. Northwestern Univ, Sch Med, Chicago, IL USA. St Josephs Hosp & Med Ctr, Dept Pediat, Newark, NJ USA. RP Kline, MW (reprint author), Baylor Coll Med, Dept Pediat, 1 Baylor Plaza, Houston, TX 77030 USA. NR 24 TC 34 Z9 34 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1998 VL 101 IS 2 BP 214 EP 220 DI 10.1542/peds.101.2.214 PG 7 WC Pediatrics SC Pediatrics GA YU816 UT WOS:000071758100005 PM 9445494 ER PT J AU Gergen, PJ Fowler, JA Maurer, KR Davis, WW Overpeck, MD AF Gergen, PJ Fowler, JA Maurer, KR Davis, WW Overpeck, MD TI The burden of environmental tobacco smoke exposure on the respiratory health of children 2 months through 5 years of age in the United States: Third National Health and Nutrition Examination Survey, 1988 to 1994 SO PEDIATRICS LA English DT Article DE environmental tobacco smoke (ETS); asthma; wheeze; chronic bronchitis; children; attributable risk ID PASSIVE-SMOKING; CHILDHOOD ASTHMA; MATERNAL SMOKING; PARENTAL SMOKING; URINARY COTININE; 1ST YEAR; ILLNESS; INFANTS; FAMILY; LIFE AB Objective. To measure the effect of environmental tobacco smoke (ETS) on respiratory health in a national sample of young children. Methods. The study evaluated children 2 months through 5 years of age participating in the Third National Health and Nutrition Examination Survey, 1988 to 1994. The group was a representative sample of the US population (N = 7680). A parental report of household smoking or maternal smoking during pregnancy ascertained ETS exposure, Respiratory outcomes were based on parental report of wheezing, cough, upper respiratory infection, or pneumonia in the last 12 months and chronic bronchitis or physician-diagnosed asthma at any time. Logistic regression was used to adjust for age, sex, race/ethnicity, birth weight, day care, family history of allergy, breastfeeding, education level of head of household, and household size. Results. Approximately 38% of children were presently exposed to ETS in the home, whereas 23.8% were exposed by maternal smoking during pregnancy. ETS exposure increased chronic bronchitis and three or more episodes of wheezing among children 2 months to 2 years old and asthma among children 2 months to 5 years old. For household exposure, a consistent effect was seen only at greater than or equal to 20 cigarettes smoked per day. Adjusted odds ratios for increased risk (95% confidence interval) for household exposures greater than or equal to 20 cigarettes smoked per day vs none smoked) and maternal prenatal exposure (prenatal smoking vs no smoking), respectively, for children 2 months to 2 years old were chronic bronchitis, 2.5 (1.6, 4.1); 2.2, (1.6, 3); three or more episodes of wheezing, 2.7 (1.7, 4.2), 2.1 (1.5, 2.9); and for children 2 months to 5 years old were asthma, 2.1 (1.4, 3.2); 1.8 (1.3, 2.6). Reported use within the past month of prescription medications for asthma (beta-agonists or inhaled steroids) was not different between those with asthma reporting ETS exposure and those reporting no exposure; percent of patients with asthma reporting use of medication by household exposure was 0, 25.7%; 1 to 19 cigarettes smoked per day, 32.9%; and greater than or equal to 20 cigarettes smoked per day, 23.1%; percent of patients with asthma reporting use of medication by maternal smoking during pregnancy was no, 28.9%; yes, 22.7%. Among children 2 months to 2 years of age exposed to ETS, 40% to 60% of the cases of asthma, chronic bronchitis, and three or more episodes of wheezing were attributable to ETS exposure, For diagnosed asthma among children 2 months through 5 years old, there were 133 800 to 161 600 excess cases. Among exposed children 2 months through 2 years of age, there were 61 000 to 79 200 excess cases of chronic bronchitis and 126 700 to 172 000 excess cases of three or more episodes of wheezing. Conclusions. ETS exposure is common among children in the United States. The reported prevalence of asthma, wheezing, and chronic bronchitis was increased with ETS exposures. No statistically significant increase in the prevalence of upper respiratory infection, pneumonia, or cough was associated with ETS exposure. ETS exposure has little effect on the respiratory health of children between 3 and 5 years of age, with the exception of asthma. ETS appears to increase the prevalence of asthma rather than the severity as measured by medication use. These findings reinforce the need to reduce the exposure of young children to ETS. C1 CPCR, Agcy Hlth Care Policy & Res, Rockville, MD 20852 USA. Klemm Anal Grp Inc, Hyattsville, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Care Stat, Hyattsville, MD USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Gergen, PJ (reprint author), CPCR, Agcy Hlth Care Policy & Res, Room 502,2101 E Jefferson St, Rockville, MD 20852 USA. NR 37 TC 154 Z9 158 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1998 VL 101 IS 2 BP art. no. EP e8 DI 10.1542/peds.101.2.e8 PG 6 WC Pediatrics SC Pediatrics GA YU816 UT WOS:000071758100026 PM 9445518 ER PT J AU Sneed, CD McCrae, RR Funder, DC AF Sneed, CD McCrae, RR Funder, DC TI Lay conceptions of the five-factor model and its indicators SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article ID 5-FACTOR MODEL; PERSONALITY AB The five-factor model (FFM) of personality is implicit in lay conceptions of personality; this research sought to examine laypersons' explicit grasp Of the model. In one study, undergraduates (N = 233) were given definitions of the five factors and asked to identify adjectives known to be associated with each. In a second study, the rated diagnosticity of behaviors in three contexts was compared with their actual correlation with self-reported and acquaintance-rated personality factors. In the final study, undergraduates (N = 76) grouped 30 adjectives into clusters of traits. Results suggest that most laypersons can easily grasp the nature of the factors and their behavioral manifestations and can spontaneously recognize their grouping when provided with clear exemplars. C1 Univ Calif Los Angeles, Sch Publ Hlth, Ctr Hlth Sci, Los Angeles, CA 90095 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif Riverside, Riverside, CA 92521 USA. RP Sneed, CD (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Ctr Hlth Sci, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 30 TC 29 Z9 29 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD FEB PY 1998 VL 24 IS 2 BP 115 EP 126 DI 10.1177/0146167298242001 PG 12 WC Psychology, Social SC Psychology GA YU788 UT WOS:000071754500001 ER PT J AU He, XJ Kuijpers, GAJ Goping, G Kulakusky, JA Zheng, CY Delporte, C Tse, CM Redman, RS Donowitz, M Pollard, HB Baum, BJ AF He, XJ Kuijpers, GAJ Goping, G Kulakusky, JA Zheng, CY Delporte, C Tse, CM Redman, RS Donowitz, M Pollard, HB Baum, BJ TI A polarized salivary cell monolayer useful for studying transepithelial fluid movement in vitro SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE salivary gland; epithelial cell; polarity; protein targeting; aquaporin-1; facilitated fluid movement ID EPITHELIAL-CELLS; RAT; GLAND; LINE AB There are no reported, convenient in vitro models for studying polarized functions in salivary epithelial cells. Accordingly, we examined three often-used salivary cell lines for their ability to form a polarized monolayer on permeable, collagen-coated polycarbonate filters. Only the SMIE line, derived from rat submandibular gland, had this ability. The SMIE cell monolayer exhibited junctional complexes, with a tight-junction-associated protein, ZO-1, localized to cell-cell contact areas. The Na+/K+-ATPase alpha(1)-subunit was detected predominantly in the basolateral membranes, while the Na+/H+ exchanger isoform 2 appeared primarily in the apical membranes. Using adenovirus-mediated cDNA transfer, SMIE cells were shown to be capable of routing marker proteins (beta-galactosidase +/- nuclear targeting signal, alpha(1)-antitrypsin, aquaporin-1) to appropriate locations. Furthermore, this salivary cell monolayer provided a convenient tool for studying aquaporin-1-mediated, osmotically directed, transepithelial fluid movement in vitro. Thus, SMIE cells appear to be a useful experimental model with which to study some polarized functions in a salivary epithelial cell line. C1 NIDR, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Div Gastroenterol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA. Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC 20422 USA. RP Baum, BJ (reprint author), NIDR, Gene Therapy & Therapeut Branch, 10 Ctr Dr,MSC 1190,Bldg 10,Rm 1N113, Bethesda, MD 20892 USA. NR 28 TC 33 Z9 34 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD FEB PY 1998 VL 435 IS 3 BP 375 EP 381 DI 10.1007/s004240050526 PG 7 WC Physiology SC Physiology GA YT856 UT WOS:000071651900008 PM 9426293 ER PT J AU Long, RM AF Long, RM TI News from the National Institute of General Medical Sciences (NIGMS) SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material C1 NIGMS, Div Pharmacol Physiol & Biol Chem, PPBC, Pharmacol & Physiol Sci PPS Branch,NIH, Bethesda, MD 20892 USA. RP Long, RM (reprint author), NIGMS, Div Pharmacol Physiol & Biol Chem, PPBC, Pharmacol & Physiol Sci PPS Branch,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD FEB PY 1998 VL 15 IS 2 BP 165 EP 166 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZA124 UT WOS:000072331300001 ER PT J AU Hughes, NC Janezic, SA McQueen, KL Jewett, MAS Castranio, T Bell, DA Grant, DM AF Hughes, NC Janezic, SA McQueen, KL Jewett, MAS Castranio, T Bell, DA Grant, DM TI Identification and characterization of variant alleles of human acetyltransferase NAT1 with defective function using p-aminosalicylate as an in-vivo and in-vitro probe SO PHARMACOGENETICS LA English DT Article DE acetyltransferase; allelic variants; NAT1; pharmacogenetics ID ARYLAMINE N-ACETYLTRANSFERASE; HUMAN LIVER; ACETYLATION PHARMACOGENETICS; MOLECULAR-GENETICS; ESCHERICHIA-COLI; EXPRESSION; PHENOTYPE; POLYMORPHISM; MECHANISM; GENOTYPE AB Although several variant alleles at the human NAT1 gene locus have been reported, their relationship to phenotypic variations in NAT1 function remains unclear. We have used in-vivo and in-vitro phenotyping tests, along with PCR-based cloning and heterologous expression, to investigate the extent of variation in NAT1 function and to characterize novel allelic variants at the NAT1 gene locus. The NAT1-selective substrate p-aminosalicylic acid (PAS) was used as a probe for NAT1 function. In-vivo PAS acetylation rates were estimated by determining the ratio of PAS to N-acetylated PAS (AcPAS) in urine and plasma following the oral ingestion of Nemasol Sodium(R). Excluding outliers, a 65-fold variation in the urinary AcPAS:PAS ratio was observed (n = 144), while a 5.6-fold variation in the plasma AcPAS: PAS ratio was seen in a subset (n = 19) of this sample. Urinary and plasma ratios correlated moderately (r = 0.74, p < 0.0005). One individual (case 244) had a marked impairment of PAS N-acetylation, with 10-fold lower urinary and plasma AcPAS: PAS ratios compared with other subjects. Biochemical investigations in whole blood lysates from case 244 suggested a NAT1 kinetic defect, with a 20-fold increased apparent K-m for PAS and a 90-fold decreased V-max for AcPAS formation. We subcloned, sequenced and expressed the protein-coding regions of the NAT1 alleles from case 244 and from seven other selected probands. Sequence analysis revealed the presence of two new variant alleles, designated as NAT1*14 and NAT1*15, in case 244, as well as one variant, NAT1*11, which has been observed in previous investigations. NAT1*14 contained a missense mutation (G(560)-->A) that is predicted to change a single amino acid (Arg(187)-->Gln), as well as two 3' non-coding region mutations (T-1088-->A and C-1095-->A) that have previously been observed in the NAT1*10 allelic variant. NAT1*15 had a single nonsense mutation (C-559-->T; Arg(187)-->stop) and, thus, encodes a truncated protein. The activity of recombinant NAT1*14 mirrored the defective enzyme function in whole blood lysates from case 244, while NAT1 15 was completely inactive. Expressed NAT1 11, on the other hand, had identical activity to the wild type NAT1 4 allele, suggesting that the coding region mutations in this variant are functionally silent. The frequencies of NAT1*11, NAT1*14 and NAT1*15 were 0.021, 0.028 and 0.014 (n = 288 alleles), respectively, suggesting that they are relatively rare in sample. (C) 1998 Chapman & Hall Ltd. C1 Hosp Sick Children, Div Clin Pharmacol & Toxicol, Res Inst, Toronto, ON M5G 1X8, Canada. Toronto Hosp, Div Urol, Toronto, ON M5T 2S8, Canada. NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Grant, DM (reprint author), Hosp Sick Children, Div Clin Pharmacol & Toxicol, Res Inst, Toronto, ON M5G 1X8, Canada. NR 36 TC 96 Z9 98 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1998 VL 8 IS 1 BP 55 EP 66 DI 10.1097/00008571-199802000-00008 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YY775 UT WOS:000072183800008 PM 9511182 ER PT J AU Yamamoto, Y Tasaki, T Nakamura, A Iwata, H Kazusaka, A Gonzalez, FJ Fujita, S AF Yamamoto, Y Tasaki, T Nakamura, A Iwata, H Kazusaka, A Gonzalez, FJ Fujita, S TI Molecular basis of the Dark Agouti rat drug oxidation polymorphism: Importance of CYP2D1 and CYP2D2 SO PHARMACOGENETICS LA English DT Article DE bunitrolol; CYP2D; cytochrome P450; polymorphism; poor metabolizer ID DEBRISOQUINE 4-HYDROXYLASE ACTIVITY; LIVER-MICROSOMES; BUNITROLOL 4-HYDROXYLATION; ANTIPEPTIDE ANTIBODIES; GENETIC-POLYMORPHISM; CATALYTIC PROPERTIES; PURIFICATION; CYTOCHROME-P-450; METABOLISM; SUBFAMILY AB The Dark Agouti rat has been proposed as a model for the human debrisoquine 4-hydroxylase polymorphism. Earlier studies suggested that the poor metabolizer phenotype in the Dark Agouti rat is caused by the absence of the expression of CYP2D1 mRNA. Although CYP2D1 is the major enzyme catalyzing debrisoquine 4-hydroxylation, other reports have indicated the involvement of a CYP2D, purified from rat hepatic microsomes and presumed to be CYP2D2, which also exhibits this activity. The levels of CYP2D1 and CYP2D2 mRNAs were markedly lower in Dark Agouti as compared to Sprague Dawley rats. Using a baculovirus expression system, recombinant CYP2D1 and CYP2D2 from Spodoptera frugiperda insect cells were examined and were found to both forms catalize debrisoquine 4-hydroxylase activity. These results suggest that reduced debrisoquine 4-hydroxylase activity in the Dark Agouti rat is caused by the low level expression not only of CYP2D1, but also of CYP2D2. Interestingly, bunitrolol 4-hydroxylation was catalyzed by recombinant CYP2D2, while CYP2D1 was inactive toward this substrate. Thus, the low bunitrolol 4-hydroxylation in Dark Agouti rats was caused by the low level of CYP2D2 expression in this rat strain. (C) 1998 Chapman & Hall Ltd. C1 Hokkaido Univ, Grad Sch Vet Med, Toxicol Lab, Sapporo, Hokkaido 060, Japan. NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Fujita, S (reprint author), Hokkaido Univ, Grad Sch Vet Med, Toxicol Lab, Sapporo, Hokkaido 060, Japan. RI Iwata, Hisato/A-5478-2013 OI Iwata, Hisato/0000-0002-6867-0532 NR 37 TC 44 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1998 VL 8 IS 1 BP 73 EP 82 DI 10.1097/00008571-199802000-00010 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YY775 UT WOS:000072183800010 PM 9511184 ER PT J AU Tella, SR Goldberg, SR AF Tella, SR Goldberg, SR TI Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE behavior; blood pressure; cardiovascular; cocaine; dopamine; monoamine uptake; inhibition; sodium channel blockade ID CONSCIOUS SQUIRREL-MONKEYS; D2 DOPAMINE ANTAGONISTS; CENTRAL-NERVOUS-SYSTEM; INTRAVENOUS COCAINE; NONHUMAN-PRIMATES; BINDING-SITES; CARDIOVASCULAR-RESPONSES; RATS; HUMANS; DRUGS AB Intravenous (IV) cocaine (0.03-3 mg/kg) produced dose-dependent, rapid, and brief increases in blood pressure (BP) in conscious rats pretreated with the dopamine receptor antagonist, SCH 23390, Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, beta CIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced this rapid presser response, whereas structurally unrelated uptake inhibitors with diverse monoamine transporter selectivities (BTCP, indatraline, GBR 12935, mazindol, nomifensine, and zimeldine) either did not produce a rapid presser response or produced only a small presser response. At nonconvulsant doses, the sodium channel blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and tetracaine produced a small presser response or no increase in BP. In rats implanted with telemetric devices, cocaine and its analog, CFT, produced a biphasic pharmacological response that consisted of an initial brief and abrupt behavioral arousal associated with a rapid; large increase in BP followed by prolonged, parallel increases in BP and locomotor activity. Pretreatment with SCH 23390 prevented the prolonged but not the initial rapid and brief presser and activity responses to both cocaine and CFT. administration. The present data suggest that the inhibition of dopamine, norepinephrine, or serotonin transporter functions, either alone or in combination, does not mediate the rapid presser response to cocaine. The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid presser response to cocaine. Finally, the present results confirm previous findings that dopaminergic mechanisms mediate the prolonged increases in BP and locomotor activity produced by cocaine. (C) 1998 Elsevier Science Inc. C1 Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. NIDA, Behav Pharmacol & Genet Sect, Preclin Pharmacol Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Tella, SR (reprint author), Georgetown Univ, Sch Med, Dept Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NIDA NIH HHS [DA08830] NR 58 TC 19 Z9 19 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1998 VL 59 IS 2 BP 305 EP 312 DI 10.1016/S0091-3057(97)00448-6 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA YU254 UT WOS:000071697700007 PM 9476974 ER PT J AU Helsley, S Filipink, RA Bowen, WD Rabin, RA Winter, JC AF Helsley, S Filipink, RA Bowen, WD Rabin, RA Winter, JC TI The effects of sigma, PCP, and opiate receptor ligands in rats trained with ibogaine as a discriminative stimulus SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ibogaine; drug discrimination; radioligand binding; sigma receptors; NMDA antagonists; opiate receptors ID ANTI-ADDICTIVE DRUG; NMDA-RECEPTOR; RADIOLIGAND-BINDING; PRIMARY METABOLITE; MK-801 BINDING; H-3 DOPAMINE; MORPHINE; AFFINITY; SITE; CONGENERS AB Although the mechanism of action of ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains un known, receptor binding studies suggest that ibogaine produces its effects via interactions with multiple receptor types. In addition to serotonergic receptors, which have been studied previously with respect to ibogaine, likely candidates include opiate, ate, sigma (sigma), and phencyclidine (PCP) binding sites. In an attempt to determine which of these receptor interactions are involved in the in vivo effects of ibogaine, ligands for sigma, PCP, and opiate receptors were assessed for their ability to substitute for or to antagonize the ibogaine-induced discriminative stimulus (10 mg/kg IF, 60 min presession) in Fischer-344 rats. Inter mediate levels of generalization were observed with the subtype nonselective sigma ligands 3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] (69.0%) and 1,3-di(2-tolyl)guanidine (DTG) (73.5%) but not with the sigma(1)-selective agents (+)-N-allylnormetazocine [(+)-SKF 10,047] and (+)-pentazocine. These findings, along with observations that ibogaine has appreciable affinity for sigma(2) receptors, suggest that these receptors may be involved in the ibogaine discriminative stimulus. With regard to opiate receptors, neither morphine, the prototypic mu agonist, nor kappa selective agonists (bremazocine,and U-50488) substituted for ibogaine. However, intermediate levels of generalization were observed with the mixed action opiates (-)-SKF 10,047 (78.9%), (+/-)-pentazocine (73.9%), nalorphine (70.4%), and diprenorphine (75.0%) indicating a potential role for opiate receptors in the ibogaine stimulus. Partial substitution was also observed with naltrexone (55.6%) but not with naloxone or the selective kappa antagonist nor-binaltorphimine (nor-BNI). These agents were largely ineffective as antagonists of the ibogaine cue, although naloxone produced a moderate but statistically significant antagonism (69.8%). In addition, naloxone produced complete antagonism of the ibogaine-appropriate responding elicited by both (-)-SKF 10,047 (19.7%) and nalorphine (25.8%), whereas the ibogaine appropriate responding produced by diprenorphine was only partially antagonized (44.4%). The latter observations taken together with the finding that both nalorphine (>100 mu M) and diprenorphine (30 mu M) have extremely low affinity for sigma(2)-receptors, suggest that the ibogaine-appropriate responding produced by these agents is not mediated by sigma(2) receptors. These findings imply that opiate effects may be involved in the ibogaine stimulus. In contrast to sigma(2) and opiate receptors, ibogaine's reported interactions with NMDA receptors do not appear to be involved in its discriminative stimulus, as neither PCP nor MK-801 produced a significant level of ibogaine appropriate responding. Thus, the present study offers evidence that unlike NMDA receptors,both sigma(2) and opiate receptors may be involved in the ibogaine discriminative stimulus. (C) 1998 Elsevier Science Inc. C1 SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Helsley, S (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, 102 Farber Hall, Buffalo, NY 14214 USA. FU NIDA NIH HHS [DA 05735, DA 03385] NR 62 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1998 VL 59 IS 2 BP 495 EP 503 DI 10.1016/S0091-3057(97)00454-1 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA YU254 UT WOS:000071697700033 PM 9477000 ER PT J AU Romero, R Dombrowski, M Sokol, RJ AF Romero, R Dombrowski, M Sokol, RJ TI Obituary: Sidney F. Bottoms, MD, 1950-1996 SO PRENATAL AND NEONATAL MEDICINE LA English DT Biographical-Item C1 Wayne State Univ, Hutzel Hosp, NICHHD, Perinatol Res Branch, Detroit, MI 48202 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Wayne State Univ, Hutzel Hosp, Sch Med, Detroit, MI 48202 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHHD, Perinatol Res Branch, Detroit, MI 48202 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1359-8635 J9 PRENAT NEONAT MED JI Prenat. Neonatal Med. PD FEB PY 1998 VL 3 IS 1 BP 2 EP 2 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA ZW380 UT WOS:000074405200002 ER PT J AU Klebanoff, MA AF Klebanoff, MA TI Conceptualizing categories of preterm birth SO PRENATAL AND NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Preterm Birth - Etiology, Mechanisms and Prevention CY OCT 26-28, 1997 CL CHARLESTON, SOUTH CAROLINA DE preterm; premature rupture of membranes (PROM); hypertension; fetal growth restriction ID SPONTANEOUS PREMATURE DELIVERY; GROWTH-RETARDATION C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Klebanoff, MA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg Room 7B03, Bethesda, MD 20892 USA. NR 16 TC 19 Z9 20 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1359-8635 J9 PRENAT NEONAT MED JI Prenat. Neonatal Med. PD FEB PY 1998 VL 3 IS 1 BP 13 EP 15 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA ZW380 UT WOS:000074405200005 ER PT J AU Krasnegor, NA Fifer, W Maulik, D McNellis, D Romero, R Smotherman, W AF Krasnegor, NA Fifer, W Maulik, D McNellis, D Romero, R Smotherman, W TI Fetal behavioral development: a transdisciplinary perspective for assessing fetal well-being and predicting outcome SO PRENATAL AND NEONATAL MEDICINE LA English DT Editorial Material C1 NICHHD, Human Learning & Behav Branch, Bethesda, MD 20892 USA. New York State Psychiat Inst, Dept Psychiat & Pediat, New York, NY USA. Winthrop Univ Hosp, Dept Obstet & Gynecol, Mineola, NY 11501 USA. NICHD, Pregnancy & Perinatol Branch, Bethesda, MD USA. NICHD, Hutzel Hosp, Dept Obstet & Gynaecol, Perinatol Res Branch, Detroit, MI USA. SUNY Binghamton, Dept Psychol, Ctr Dev Psychobiol, Binghamton, NY USA. RP Krasnegor, NA (reprint author), NICHHD, Human Learning & Behav Branch, 6100 Execut Blvd,Room 4B05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 2 TC 12 Z9 12 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1359-8635 J9 PRENAT NEONAT MED JI Prenat. Neonatal Med. PD FEB PY 1998 VL 3 IS 1 BP 185 EP 188 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA ZW380 UT WOS:000074405200044 ER PT J AU Ghidini, A Spong, CY Grier, RE Walker, CN Pezzullo, JC AF Ghidini, A Spong, CY Grier, RE Walker, CN Pezzullo, JC TI Is maternal serum triple screening a better predictor of Down syndrome in female than in male fetuses? SO PRENATAL DIAGNOSIS LA English DT Article DE prenatal diagnosis; trisomy 21; fetal gender ID ALPHA-FETOPROTEIN; FETAL SEX; RATIO AB Among euploid gestations, female fetuses have been reported to have significantly lower maternal serum alpha-fetoprotein (MSAFP) and higher human chorionic gonadotropin (hCG) levels than male fetuses. Since in maternal serum triple screening, low MSAFP and high hCG MOM independently confer greater risk of a Down syndrome fetus, we investigated the hypothesis that maternal serum triple screening is more efficacious at detecting female than male Down syndrome fetuses. A database containing all karyotypes from amniocentesis performed between August 1994 and August 1996 was accessed. All trisomy 21 cases were identified. The male-to-female ratio among trisomy 21 fetuses detected at amniocentesis after abnormal maternal serum triple screening was compared with that among trisomy 21 fetuses detected at amniocentesis for advanced maternal age (AMA), which served as the control group. Statistical analysis utilized chi-square, Fisher's exact test, and Student's t-test. A P value of less than 0.05 was considered statistically significant. Forty-nine trisomy 21 fetuses were detected in the women who underwent amniocentesis because of abnormal triple screening and 311 were detected in the control group. The proportion of male fetuses among the triple screening group was not significantly different from that of the AMA group (55 per cent vs. 57 per cent; P=0.9). Our study had a power of 80 per cent to detect a difference of 25 per cent in the male-to-female ratio (alpha=0.05, beta=0.20). The reported differences in MSAFP and hCG levels between male and female euploid fetuses do not appear to affect the sex ratio among Down syndrome fetuses detected because of an abnormal maternal serum triple screening. (C) 1998 John Wiley & Sons, Ltd. C1 Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Biostat & Biomath, Washington, DC 20007 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD USA. Genzyme Genet, Santa Fe, NM USA. RP Ghidini, A (reprint author), Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, 3800 Reservoir Rd NW,3PHC, Washington, DC 20007 USA. NR 9 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD FEB PY 1998 VL 18 IS 2 BP 123 EP 126 DI 10.1002/(SICI)1097-0223(199802)18:2<123::AID-PD221>3.0.CO;2-6 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA YZ237 UT WOS:000072234000004 PM 9516012 ER PT J AU Robinson, RA Burgess, WH Emerson, SU Leibowitz, RS Sosnovtseva, SA Tsarev, S Purcell, RH AF Robinson, RA Burgess, WH Emerson, SU Leibowitz, RS Sosnovtseva, SA Tsarev, S Purcell, RH TI Structural characterization of recombinant hepatitis E virus ORF2 proteins in baculovirus-infected insect cells SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID TRANSMITTED NON-A; NON-B HEPATITIS; CYNOMOLGUS MONKEYS; MOLECULAR-CLONING; PROTOTYPE STRAIN; SEQUENCE; HEV; PURIFICATION; ISOLATE; GENOME AB The hepatitis E virus (HEV) capsid antigen has been proposed as a candidate subunit vaccine for the prevention of hepatitis E. The full-length HEV ORF2 protein product is predicted to contain 660 amino acids and to weigh 72,000 daltons. Expression of the HEV ORF2 capsid gene from recombinant baculoviruses in insect cells produced multiple immunoreactive proteins ranging in size from 30 to 100 kDa. The most abundant HEV proteins had molecular weights of 72, 63, 56, and 53 kDa. Temporal expression kinetics of these viral polypeptides indicated that the 72- and 63-kDa polypeptides were produced abundantly within the initial 36 h. postinfection but were replaced by 56- and 53-kDa polypeptides in the cell and medium, respectively, by 48 h postinfection. The 53-kDa protein was secreted as early as 24 h. postinfection, and accumulation in the medium peaked by 72 h postinfection. Purification of the 53-, 56-, and 63-kDa viral polypeptides was accomplished by anion-exchange and subsequent gel filtration chromatography. Sequence analysis of the 53-, 56-, and 63-kDa HEV polypeptides indicated that the amino terminus was amino acid residue 112 of the predicted full-length protein product. The results of carboxy terminal amino acid sequencing indicated that the carboxy terminus of the 53-, 56-, and 63-kDa HEV proteins was located at amino acid residues 578, 607, and 660, respectively. The molecular masses of the 53- and 56-kDa HEV polypeptides were 53,872 and 56,144 as determined by mass spectroscopy. (C) 1998 Academic Press. C1 Dyncorp, Mol Virol Lab, Rockville, MD 20850 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD 20855 USA. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Virus Dis, Washington, DC 20307 USA. RP Robinson, RA (reprint author), Dyncorp, Mol Virol Lab, 1 Taft Court, Rockville, MD 20850 USA. FU NIAID NIH HHS [N01-AI-35154, N01-AI-05069] NR 22 TC 83 Z9 88 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 1998 VL 12 IS 1 BP 75 EP 84 DI 10.1006/prep.1997.0817 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YY157 UT WOS:000072119000011 PM 9473460 ER PT J AU Clardy, JA Booth, BM Smith, LG Nordquist, CR Smith, GR AF Clardy, JA Booth, BM Smith, LG Nordquist, CR Smith, GR TI Implementing a statewide outcomes management system for consumers of public mental health services SO PSYCHIATRIC SERVICES LA English DT Article ID CARE REFORM; QUALITY; DEPRESSION; CHALLENGE; AGENCIES; COSTS AB The authors describe the development and implementation of an outcomes management system designed to measure outcomes and processes of care for public mental health consumers in Arkansas. The public-academic project was implemented in 1995 and is based on the Shewhart-Deming model of continuous duality improvement. All 15 community mental health centers (CMHCs) in the state participate in the project, which prospectively measures longitudinal outcomes of care for the tracer conditions of major depression and schizophrenia. Multiperspective measurement tools are used to measure patients' psychiatric status and general health status at periodic intervals; information is gathered on functioning, symptoms, severity of illness, social factors, demographic characteristics, and quality of life. A problem encountered during implementation was the relatively low rate of referral of patients with the tracer conditions for monitoring. Voluntary rather than mandatory participation in the outcomes management system by the CMHCs as well as clinicians' misperceptions about the system's purpose and concerns about confidentiality may have partly accounted for the low rate. C1 Univ Arkansas Med Sci, NIMH, Ctr Mental Healthcare Res, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, NIMH, Dept Psychiat, Little Rock, AR 72205 USA. RP Clardy, JA (reprint author), Univ Arkansas Med Sci, NIMH, Ctr Mental Healthcare Res, 4301 W Markham St,Slot 589, Little Rock, AR 72205 USA. NR 39 TC 18 Z9 18 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1998 VL 49 IS 2 BP 191 EP 195 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA YV307 UT WOS:000071810100007 PM 9575003 ER PT J AU Pinals, DA Malhotra, AK Breier, A Pickar, D AF Pinals, DA Malhotra, AK Breier, A Pickar, D TI Informed consent in schizophrenia research SO PSYCHIATRIC SERVICES LA English DT Letter C1 N Coast Behav Healthcare Syst, Northfield, OH USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Pinals, DA (reprint author), N Coast Behav Healthcare Syst, Northfield, OH USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1998 VL 49 IS 2 BP 244 EP 244 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA YV307 UT WOS:000071810100020 PM 9575016 ER PT J AU Hawkins, WE Latkin, C Hawkins, MJ Chowdury, D AF Hawkins, WE Latkin, C Hawkins, MJ Chowdury, D TI Depressive symptoms and HIV-risk behavior in inner-city users of drug injections SO PSYCHOLOGICAL REPORTS LA English DT Article AB The association of HIV risk-taking behavior with frequency of depressive symptoms varied by specific risk behavior and amount of harm reduction of behavior of men and women (N = 642), 80% of whom were African-American. C1 Catholic Univ Amer, Natl Council Sch Social Serv, Natl Catholic Sch Social Serv, Washington, DC 20001 USA. NIDA, Lexington, KY 40583 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Portland State Univ, Portland, OR 97207 USA. RP Hawkins, MJ (reprint author), Catholic Univ Amer, Natl Council Sch Social Serv, Natl Catholic Sch Social Serv, Shahan Hall, Washington, DC 20001 USA. NR 5 TC 14 Z9 14 U1 0 U2 0 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 USA SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD FEB PY 1998 VL 82 IS 1 BP 137 EP 138 DI 10.2466/PR0.82.1.137-138 PG 2 WC Psychology, Multidisciplinary SC Psychology GA YZ189 UT WOS:000072229200029 PM 9520544 ER PT J AU Pickworth, WB Fant, RV AF Pickworth, WB Fant, RV TI Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 6th Nicotine Round Table Satellite Meeting CY NOV 15, 1996 CL WASHINGTON, D.C. SP Amer Soc Addict Med Nicotine Dependence DE ACTH; cortisol; prolactin; nicotine; cocaine; opiate; ethanol; withdrawal ID CIGARETTE-SMOKING; SYNAPTIC TRANSMISSION; ALCOHOL-WITHDRAWAL; COCAINE WITHDRAWAL; BETA-ENDORPHIN; FREE CORTISOL; NEUROENDOCRINE; PROLACTIN; SMOKERS; RESPONSES AB The focus of this manuscript is on the effects of smoking and tobacco withdrawal on the hypothalamic-pituitary axis (HPA). A variety of studies have shown that nicotine administered intravenously or through intense cigarette smoking can induce changes in hormones associated with the HPA. Administration of, and abrupt cessation from, other drugs of abuse has also been shown to affect levels of these hormones. Additionally, many of the symptoms of stress and tobacco withdrawal overlap suggesting that the hormonal changes seen during periods of stress may be observed during tobacco abstinence. These findings led to a study of the effects of tobacco withdrawal on plasma ACTH, cortisol, and prolactin levels. The results indicated tobacco cessation caused small and transient effects on plasma hormone levels which were not significantly influenced by nicotine replacement and were not related to other signs of withdrawal. Published by Elsevier Science Ltd. C1 NIDA, Clin Pharmacol Branch, Addict Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Pickworth, WB (reprint author), NIDA, Clin Pharmacol Branch, Addict Res Ctr, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. NR 55 TC 44 Z9 45 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD FEB PY 1998 VL 23 IS 2 BP 131 EP 141 DI 10.1016/S0306-4530(97)00075-9 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA ZN571 UT WOS:000073659200004 PM 9621394 ER PT J AU Meyer, RC Knox, J Purwin, DA Spangler, EL Ingram, DK AF Meyer, RC Knox, J Purwin, DA Spangler, EL Ingram, DK TI Combined stimulation of the glycine and polyamine sites of the NMDA receptor attenuates NMDA blockade induced learning deficits of rats in a 14-unit T-maze SO PSYCHOPHARMACOLOGY LA English DT Article DE glutamate; D-cycloserine; spermine; memory; neurotransmitter; calcium; Alzheimer's disease ID FEAR-POTENTIATED STARTLE; D-ASPARTATE RECEPTOR; D-CYCLOSERINE; CHOLINERGIC HYPOTHESIS; COGNITIVE ENHANCEMENT; MEMORY DEFICITS; AGED RATS; LONG-TERM; ANTAGONIST; PERFORMANCE AB The present study examined the effects of multi-site activation of the glycine and polyamine sites of the NMDA receptor on memory formation in rats learning a 14-unit T-maze task. The competitive NMDA receptor antagonist, (+/-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 9 mg/kg), was used to impair learning. The objectives were twofold: (I) to investigate the effects of independent stimulation of the strychnine-insensitive glycine site or the polyamine site; (2) to investigate the effects of simultaneous activation of these two sites. Male, Fischer-344 rats were pretrained to a criterion of 13 out of 15 shock avoidances in a straight runway, and 24 h later were trained in a 14-unit T-maze that also required shock avoidance. Prior to maze training, rats received intraperitoneal(IP) injections of saline, saline plus CPP, CPP plus the glycine agonist, D-cycloserine (DCS, 30 or 40 mg/kg), CPP plus the polyamine agonist, spermine (SPM, 2.5 or 5 mg/kg), or CPP plus a combination of DCS (7.5 mg/kg) and SPM (0.625 mg/kg). Individual administration of either DCS or SPM attenuated the CPP-induced maze learning impairment in a dose-dependent manner. However, the combined treatment with both DCS and SPM completely reversed the learning deficit at doses five-fold less than either drug given alone. These findings provide additional evidence that the glycine and polyamine modulatory sites of the NMDA receptor are involved in memory formation. Furthermore. the potent synergistic effect resulting from combined activation of the glycine and polyamine sites would suggest a stronger interaction between these two sites than previously considered, and might provide new therapeutic approaches for enhancing glutamatergic function. C1 NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Johns Hopkins Bayview Campus,5600 Nathon Shock Dr, Baltimore, MD 21224 USA. NR 46 TC 30 Z9 30 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1998 VL 135 IS 3 BP 290 EP 295 DI 10.1007/s002130050512 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YV524 UT WOS:000071833700010 PM 9498733 ER PT J AU Premkumar, A Walworth, CM Vogel, S Daryanani, KD Venzon, DJ Kovacs, JA Feuerstein, IM AF Premkumar, A Walworth, CM Vogel, S Daryanani, KD Venzon, DJ Kovacs, JA Feuerstein, IM TI Prospective sonographic evaluation of interleukin-2-induced changes in the gallbladder SO RADIOLOGY LA English DT Article DE gallbladder, US; gallbladder, wall thickening; lymphokines ID HUMAN-IMMUNODEFICIENCY-VIRUS; KILLER-CELL THERAPY; ACUTE CHOLECYSTITIS; INFECTION; CANCER; WALL; ULTRASOUND; TOXICITY AB PURPOSE: To describe the changes in the gallbladder induced by interleukin-2 (IL-2) therapy and to correlate the findings with the clinical course. MATERIALS AND METHODS: Twenty-five men with human immunodeficiency virus (HIV) infection were examined prospectively with right upper quadrant ultrasonography (US) before and after receiving IL-2 therapy. Four patients also underwent US after a second course of IL-2. The gallbladder was evaluated for wall thickening, echotexture, and intramural and pericholecystic fluid. Correlation was made between the clinical signs and symptoms, IL-2 dose, CD4 cell count, and the US appearance of the gallbladder. RESULTS: There was significant correlation between symptoms of right upper quadrant pain during IL-2 therapy and US abnormalities of the gallbladder, including an increase in wall thickening (P = .012) and the development of intramural (P = .015) and pericholecystic (P = .006) fluid. More severe abnormalities were seen with higher IL-2 doses. All symptoms resolved with cessation of IL-2 therapy. In patients who underwent repeat US, the gallbladder reverted to a normal appearance. No correlation was found between the CD4 cell count and the development of symptoms or the US appearance of the gallbladder. CONCLUSION: IL-2-induced changes resolve rapidly with cessation of therapy, and no surgical intervention is needed. These changes can be avoided or reduced by decreasing the IL-2 dose during subsequent cycles. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment Diag & Ctr, NIH, Bethesda, MD 20892 USA. RP Premkumar, A (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 20 TC 3 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1998 VL 206 IS 2 BP 393 EP 396 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YT644 UT WOS:000071627700016 PM 9457191 ER PT J AU Zeiger, E Stokes, WS AF Zeiger, E Stokes, WS TI Validating new toxicology tests for regulatory acceptance SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article AB Before a new or revised toxicology test is considered acceptable for safety evaluation of new substances, the test users and the industrial and regulatory decision makers must feel comfortable with it, and the decisions it supports. Comfort with, and the acceptance of, a new test comes after knowing that it has been validated for its proposed use. The validation process is designed to determine the operational characteristics of a test, that is, its reliability and relevance, in addition to its strengths and limitations. The reliability of a test is measured by its reproducibility. Its relevance is judged by its mechanistic relationship to the health effects of concern, and its ability to predict or identify those effects. The U.S. government has recently formed the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to work with federal agencies and test developers to coordinate the evaluation and adoption of new test methods. The ICCVAM will provide guidance to agencies and other stakeholders on criteria and processes for development, validation, and acceptance of tests; coordinate technical reviews of proposed new tests of interagency interest; facilitate information sharing among agencies; and serve as an interagency resource and communications link with parties outside of the federal government on matters of test method validation. (C) 1998 Academic Press. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Zeiger, E (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1998 VL 27 IS 1 BP 32 EP 37 DI 10.1006/rtph.1997.1178 PN 1 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA ZT330 UT WOS:000074074000005 PM 9629594 ER PT J AU Murrell, JA Portier, CJ Morris, RW AF Murrell, JA Portier, CJ Morris, RW TI Characterizing dose-response I: Critical assessment of the benchmark dose concept SO RISK ANALYSIS LA English DT Article DE benchmark dose; dose-response; risk-assessment; NOAEL; noncancer endpoints ID ADVERSE EFFECT LEVELS; RISK ASSESSMENT; DEVELOPMENTAL TOXICITY; RATS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; RECEPTOR; MICE AB We present a critical assessment of the benchmark dose (BMD) method introduced by Crump((1)) as an alternative method for setting a characteristic dose level for toxicant risk assessment. The no-observed-adverse-effect-level (NOAEL) method has been criticized because it does not use all of the data and because the characteristic dose level obtained depends on the dose levels and the statistical precision (sample sizes) of the study design. Defining the BMD in terms of a confidence bound on a point estimate results in a characteristic dose that also varies with the statistical precision and still depends on the study dose levels.((2)), Indiscriminate choice of benchmark response level may result in a BMD that reflects little about the dose-response behavior available from using all of the data. Another concern is that the definition of the BMD for the quantal response case is different for the continuous response case. Specifically, defining the BMD for continuous data using a ratio of increased effect divided by the background response results in an arbitrary dependence on the natural background for the endpoint being studied, making comparison among endpoints less meaningful and standards more arbitrary. We define a modified benchmark dose as a point estimate using the ratio of increased effect divided by the full adverse response range which enables consistent placement of the benchmark response level and provides a BMD with a more consistent relationship to the dose-response curve shape. C1 Analyt Sci Inc, Durham, NC USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Analyt Sci Inc, Durham, NC USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 42 TC 38 Z9 38 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 EI 1539-6924 J9 RISK ANAL JI Risk Anal. PD FEB PY 1998 VL 18 IS 1 BP 13 EP 26 DI 10.1111/j.1539-6924.1998.tb00911.x PG 14 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA ZB065 UT WOS:000072431500005 PM 9523441 ER PT J AU Welp, EA Weiderpass, E Boffetta, P Vainio, H Vasama-Neuvonen, K Petralia, S Partanen, TJ AF Welp, EA Weiderpass, E Boffetta, P Vainio, H Vasama-Neuvonen, K Petralia, S Partanen, TJ TI Environmental risk factors of breast cancer SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Review DE halogenated hydrocarbons; mutations; occupation; pesticides; postmenopausal women; solvents; xenoestrogens ID DRY-CLEANING WORKERS; ORGANOCHLORINE COMPOUNDS; UNITED-STATES; MORTALITY; FEMALE; HYPOTHESIS; RESIDUES; LAUNDRY; COHORT; BLACK AB Breast cancer is women's most ubiquitous cancer. The role of dietary factors is controversial, but there is limited evidence for such occupational risk factors as employment in the pharmaceutical industry and as a beautician. Ionizing radiation probably increases the risk. Exposure to chlorinated hydrocarbon pesticides, chlorinated solvents, and polychlorinated biphenyls may be risk factors, although the evidence is insufficient. Data on low-frequency electromagnetic fields are inconclusive. Tobacco smoking may be a risk factor, but the effect may depend on N-acetyltransferase 2 genetic polymorphisms. There are yet unidentified determinants, probably environmental, that may act via estrogenic activity or through other mechanisms. The etiology may vary according to the joint estrogen and progesterone receptor status of the tumor. P53 mutation frequency varies considerably in breast cancer populations, which may reflect variation in exogenous exposures. Epidemiology research on breast cancer needs to consider subtypes of the disease, lifetime exposure assessment, host susceptibility, and adjustment for reproductive and menstrual history. C1 Karolinska Inst, Dept Med Epidemiol, S-17177 Stockholm, Sweden. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. Finnish Inst Occupat Hlth, Helsingor, Denmark. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Rockville, MD USA. RP Weiderpass, E (reprint author), Karolinska Inst, Dept Med Epidemiol, POB 281, S-17177 Stockholm, Sweden. EM Elisabete.Weiderpass@MEP.KI.SE RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 NR 46 TC 30 Z9 31 U1 0 U2 3 PU SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 EI 1795-990X J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD FEB PY 1998 VL 24 IS 1 BP 3 EP 7 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZE002 UT WOS:000072747100002 PM 9562394 ER PT J AU Brocke, S Hausmann, S Steinman, L Wucherpfennig, KW AF Brocke, S Hausmann, S Steinman, L Wucherpfennig, KW TI Microbial peptides and superantigens in the pathogenesis of autoimmune diseases of the central nervous system SO SEMINARS IN IMMUNOLOGY LA English DT Review DE microbial peptide antigens; superantigens; autoimmune disease ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; STAPHYLOCOCCAL-ENTEROTOXIN-B; T-CELL RECEPTOR; MULTIPLE-SCLEROSIS PATIENTS; MEDIATED DEMYELINATING DISEASES; MAMMARY-TUMOR VIRUS; HEAT-SHOCK-PROTEIN; MOLECULAR MIMICRY; BACTERIAL SUPERANTIGEN AB The mechanisms by which microbial peptide antigens and superantigens might initiate and perpetuate autoimmune responses against antigens of the central nervous system are discussed. A model will be proposed that includes the initial activation of naive T lymphocytes through T cell receptor-mediated recognition of microbial antigens presented by MHC class II molecules. This event might be followed by re-activation of autoreactive T cells by bacterial and viral superantigens. Bath mechanisms could lead to acute and relapsing autoimmune disease. C1 NINDS, Neurol Dis Sect, NIB, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Beckman Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Brocke, S (reprint author), NINDS, Neurol Dis Sect, NIB, NIH, 10 Ctr Dr,Bldg 10,Room 5B16, Bethesda, MD 20892 USA. NR 108 TC 28 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD FEB PY 1998 VL 10 IS 1 BP 57 EP 67 DI 10.1006/smim.1997.0105 PG 11 WC Immunology SC Immunology GA 131NE UT WOS:000076581500007 PM 9529656 ER PT J AU Borden, EC Parkinson, D AF Borden, EC Parkinson, D TI A perspective on the clinical effectiveness and tolerance of interferon-alpha SO SEMINARS IN ONCOLOGY LA English DT Review ID PITUITARY-ADRENAL AXIS; CANCER-PATIENTS; INTERFERON-ALPHA-2-INDUCED STIMULATION; LYMPHOBLASTOID INTERFERON; THERAPY; HYPOTHYROIDISM; SECRETION; TOXICITY; MELANOMA; CORTISOL C1 Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. RP Borden, EC (reprint author), Univ Maryland, Ctr Canc, 22 S Green St, Baltimore, MD 21201 USA. NR 16 TC 56 Z9 57 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 SU 1 BP 3 EP 8 PG 6 WC Oncology SC Oncology GA YY633 UT WOS:000072167900002 PM 9482534 ER PT J AU LIcinio, J Kling, MA Hauser, P AF LIcinio, J Kling, MA Hauser, P TI Cytokines and brain function: Relevance to interferon-alpha-induced mood and cognitive changes SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-1-BETA CONVERTING-ENZYME; MESSENGER-RNA EXPRESSION; CORTICOTROPIN-RELEASING HORMONE; PROGRAMMED CELL-DEATH; RECOMBINANT INTERLEUKIN-2; RAT-BRAIN; CYSTEINE PROTEASE; MICROGLIAL CELLS C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. VA Med Ctr, Baltimore, MD USA. RP LIcinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10,Room 2D46,10 Ctr Dr MSC 1284, Bethesda, MD 20892 USA. RI Kling, Mitchel/F-4152-2010; Licinio, Julio/L-4244-2013 OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884 NR 97 TC 88 Z9 89 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 SU 1 BP 30 EP 38 PG 9 WC Oncology SC Oncology GA YY633 UT WOS:000072167900006 PM 9482538 ER PT J AU Zwiebel, JA Cheson, BD AF Zwiebel, JA Cheson, BD TI Chronic lymphocytic leukemia: Staging and prognostic factors SO SEMINARS IN ONCOLOGY LA English DT Review ID MULTIVARIATE SURVIVAL ANALYSIS; B-CELL LEUKEMIAS; INTERCELLULAR-ADHESION MOLECULE-1; MULTIDRUG-RESISTANCE PHENOTYPE; CHRONIC LYMPHATIC-LEUKEMIA; CHRONIC LYMPHOID LEUKEMIA; SERUM CIRCULATING LEVELS; S-TRANSFERASE ACTIVITY; BONE-MARROW HISTOLOGY; IN-SITU HYBRIDIZATION C1 NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NR 168 TC 122 Z9 128 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 BP 42 EP 59 PG 18 WC Oncology SC Oncology GA YX207 UT WOS:000072017100010 PM 9482526 ER PT J AU Dalakas, MC Mock, V Hawkins, MJ AF Dalakas, MC Mock, V Hawkins, MJ TI Fatigue: Definitions, mechanisms, and paradigms for study SO SEMINARS IN ONCOLOGY LA English DT Review ID RESECTED CUTANEOUS MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; PLACEBO-CONTROLLED TRIAL; CANCER-PATIENTS; POSTPOLIO SYNDROME; HEALTHY-INDIVIDUALS; SPINAL-CORDS; DOUBLE-BLIND; POLIOMYELITIS; INTERVENTION C1 Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Med, Washington, DC 20007 USA. Johns Hopkins Univ, Baltimore, MD USA. NINDS, Bethesda, MD 20892 USA. RP Hawkins, MJ (reprint author), Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Med, 3800 Reservoir Rd, Washington, DC 20007 USA. NR 39 TC 35 Z9 36 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 SU 1 BP 48 EP 53 PG 6 WC Oncology SC Oncology GA YY633 UT WOS:000072167900008 PM 9482540 ER PT J AU Byrd, JC Rai, KR Sausville, EA Grever, MR AF Byrd, JC Rai, KR Sausville, EA Grever, MR TI Old and new therapies in chronic lymphocytic leukemia: Now is the time for a reassessment of therapeutic goals SO SEMINARS IN ONCOLOGY LA English DT Review ID BREAST-CARCINOMA CELLS; PREVIOUSLY TREATED PATIENTS; MONOCLONAL-ANTIBODY; PHASE-I; FLUDARABINE MONOPHOSPHATE; GROWTH-INHIBITION; PURINE ANALOGS; CLINICAL-TRIAL; CYCLE ARREST; CHLORAMBUCIL C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Uniformed Serv Univ, Washington, DC USA. Long Isl Jewish Med Ctr, Div Hematol Oncol, New Hyde Park, NY 11042 USA. NCI, Dev Therapeut Program, Div Canc Treatment, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Div Hematol Malignancies, Baltimore, MD 21205 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Ward 78, Washington, DC 20307 USA. NR 93 TC 43 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 BP 65 EP 74 PG 10 WC Oncology SC Oncology GA YX207 UT WOS:000072017100012 PM 9482528 ER PT J AU Howell, MR Quinn, TC Brathwaite, W Gaydos, CA AF Howell, MR Quinn, TC Brathwaite, W Gaydos, CA TI Women for Chlamydia trachomatis in family planning clinics - The cost-effectiveness of DNA amplification assays SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; PELVIC INFLAMMATORY DISEASE; LOW-PREVALENCE POPULATION; GEN-PROBE PACE-2; ENDOCERVICAL SPECIMENS; NEISSERIA-GONORRHOEAE; ENZYME-IMMUNOASSAY; URINE SPECIMENS; CELL-CULTURE; AMPLICOR-PCR AB Background: Highly sensitive and specific DNA amplification assays are available for use on cervical and urine specimens, These new tests have the potential to identify more chlamydial infections than the commonly used enzyme immunoassay and DNA probe tests, yet they are more expensive, This study sought to assess the cost effectiveness of cell culture, enzyme immunoassay (EIA), DNA probe (Pace 2), polymerase chain reaction (PCR) of cervical and urine specimens, and ligase chain reaction (LCR) of cervical and urine specimens as screening tools for Chlamydia trachomatis in asymptomatic women younger than 30 years of age attending family planning clinics. Study Design: Program costs; medical cost savings of prevented sequelae in women, male sex partners, and infant; and number of prevented cases of pelvic inflammatory disease (PID), neonatal infections, and male sex partner urethritis and epididymitis were modeled in a decision analysis conducted from a health care system perspective. Results are expressed for a cohort of 18,000 women. Results: If no screening for C. trachomatis were conducted in Maryland, 497 cases of PID would develop, costing $2.2 million in future medical costs, Use of EIA to detect chlamydial infection would prevent 240 cases of PID and save $887,000 over no screening, Alternatively, use of DNA amplification assays on urine specimens would prevent up to an additional 66 cases and save $287,100 over EIA, Use of LCR on cervical specimens would prevent at least 13 additional cases of PLD over the urine-based assays, but would cost $3,005 for each additional case prevented, In women receiving routine pelvic examinations, LCR of cervical specimens would prevent the most disease and provide the highest cost savings, In women not receiving routine pelvic examinations, use of LCR on cervical specimens would prevent the most disease but would cost approximately $28,000 per additional case of PID prevented over DNA amplification of urine. Conclusions: Compared with ELA screening, the strategy with the lowest program costs, a screening strategy that combines use of DNA amplification on cervical specimens in women receiving pelvic examinations, and DNA amplification of urine in women with no medical indications necessitating a pelvic examination, prevents the most cases of PID and provides the highest cost savings, With enhanced sensitivity over the other diagnostic assays and with the use of noninvasive specimen collection, DNA amplification assays should be implemented as cost-effective components of a screening program for C. trachomatis. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Baltimore City Hlth Dept, Baltimore, MD USA. RP Howell, MR (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 43 TC 102 Z9 106 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD FEB PY 1998 VL 25 IS 2 BP 108 EP 117 DI 10.1097/00007435-199802000-00008 PG 10 WC Infectious Diseases SC Infectious Diseases GA YV528 UT WOS:000071834100008 PM 9518379 ER PT J AU Bertram, R Sherman, A AF Bertram, R Sherman, A TI Population dynamics of synaptic release sites SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE multiple scale analysis; stochastic system; neurotransmitter release model ID SQUID GIANT SYNAPSE; TRANSMITTER RELEASE; CALCIUM HYPOTHESIS; ION CHANNELS; TIME COURSE; HAIR-CELLS; CA2+; FACILITATION; NEUROTRANSMITTER; ACETYLCHOLINE AB We describe a mathematical model of synaptic transmitter release that is based on the finding that transmitter release sites and Ca2+ ion channels are colocalized in the presynaptic terminal. Because Ca2+ channels open and close stochastically, the release model is inherently stochastic. We develop a simple method for representing the collective effect of a population of sites and channels by constructing a system of ordinary differential equations for the mean release. A multiple scale analysis of this system reveals several features of transmitter release and fast facilitation, where release is enhanced if preceded by a conditioning impulse. These include an inverse relation between facilitation and Ca2+ cooperativity, a step-like frequency dependence of facilitation, and a release time course that is invariant to changes in the magnitude of release that occurs as the model synapse facilitates or when the external Ca2+ concentration is changed. The model is sufficiently simple to be used in conjunction with models of neuronal electrical activity and with neural network models. C1 Penn State Univ, Div Sci, Erie, PA 16563 USA. NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Bertram, R (reprint author), Penn State Univ, Div Sci, Stn Rd, Erie, PA 16563 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD FEB PY 1998 VL 58 IS 1 BP 142 EP 169 PG 28 WC Mathematics, Applied SC Mathematics GA YW498 UT WOS:000071941800008 ER PT J AU Kuller, LH Shemanski, L Manolio, T Haan, M Fried, L Bryan, N Burke, GL Tracy, R Bhadelia, R AF Kuller, LH Shemanski, L Manolio, T Haan, M Fried, L Bryan, N Burke, GL Tracy, R Bhadelia, R TI Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study SO STROKE LA English DT Article DE apolipoproteins; dementia; magnetic resonance imaging; stroke; vascular disease ID APOLIPOPROTEIN-E ALLELES; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; EPSILON-4 ALLELE; ELDERLY PEOPLE; RISK-FACTORS; EDUCATION; IMPAIRMENT; STROKE; ASSOCIATION AB Background and Purpose-We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. Methods-The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. Results-The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores, The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). Conclusions-These results demonstrate that vascular changes on MRI, measures of brain atrophy, AgoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. CHS Coordinating Ctr, Seattle, WA USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ Vermont, Colchester, VT USA. Tufts Univ, New England Med Ctr, CHS Ultrasound Lab, Boston, MA 02111 USA. RP Kuller, LH (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM kuller+@pitt.edu FU NHLBI NIH HHS [N01-HC-85081, N01-HC-85079, N01-HC-85080] NR 70 TC 225 Z9 225 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1998 VL 29 IS 2 BP 388 EP 398 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YW406 UT WOS:000071932100009 PM 9472879 ER PT J AU Lu, YF Xu, H Liu-Chen, LY Chen, CG Partilla, JS Brine, GA Carroll, FI Rice, KC Lai, J Porreca, F Sadee, W Rothman, RB AF Lu, YF Xu, H Liu-Chen, LY Chen, CG Partilla, JS Brine, GA Carroll, FI Rice, KC Lai, J Porreca, F Sadee, W Rothman, RB TI Opioid peptide receptor studies. 7. The methylfentanyl congener RTI-4614-4 and its four enantiomers bind to different domains of the rat mu opioid receptor SO SYNAPSE LA English DT Article DE (+)-3-methylfentanyl; preceptor; RTI-4614-4 ID SITE-DIRECTED MUTAGENESIS; MEDIATED PHENOMENA; OPIATE RECEPTOR; SINGLE RESIDUE; AGONIST; SELECTIVITY; AFFINITY; (+)-CIS-3-METHYLFENTANYL; LIGAND; BRAIN AB Mutational analysis of opioid receptors supports the hypothesis that dissimilar receptor domains contribute to the binding affinity of different ligands. To determine whether enantiomeric ligands can serve to distinguish between different binding pockets (which focuses the analysis on asymmetric structural factors while avoiding confounding changes in physiochemical characteristics), we analyzed the binding of the 3-methylfentanyl congeners RTI-4614-4 [(+/-)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]- N-phenylpropanamide HCl)], its four stereoisomers [(2S,3R,4S)-1a, (2R,3R,4S)-1b, (2R,3S,4R)-1c, and (2S,3S,4R)-1d], and other mu agonists with cloned rat mu opioid receptors stably expressed in HEK-293 cells and mu/kappa receptor chimeras. Chimera III (Kaminoacids 1-141/mu(aminoacids 151-398)), chimera IV (mu(aminoacids 1-150)/ kappa(aminoacids 142-380)), and chimera XII (kappa(aminoacids 1-262)/mu(aminoacids 269-398)) bound [I-125]IOXY (6 beta-iodo-3,14-dihydoxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan) with high affinities. The Ki values of 1a, 1b, 1c, and 1d at the wild-type mu receptor were 0.55 nM, 0.66 nM, 124 nM, and 59.2 nM, respectively. When the region from the N terminal to the start of the transmembrane helix 3 (TMH3) of the mu receptor was substituted by that of the kappa receptor (chimera III), the Ki value of 1b was increased (relative to the mu receptor) 590-fold compared to a 73-fold increase for 1a, When this portion of the kappa receptor was replaced by that of the mu receptor (chimera IV), the loss of affinity was not as great: 11.7-fold for 1a and 58.5-fold for 1b. Replacement of the middle of the third intracellular loop and third extracellular loop (e3) of the kappa receptor with that of the mu receptor (chimera XII) lowered (relative to their Ki values at the kappa receptor) the Ki values of [D-Ala(2),D-Leu(5)] enkephalin and [D-Ala(2)-MePhe(4),Gly-ol(5)]enkephalin to a much greater extent than the Ki values of the isomers. The kappa/chimera XlI shift was greater for isomers 1c and 1d than for 1b and 1a. Viewed collectively, these data suggest that the region from the N terminal to the start of the TMH3 of the mu opioid receptor determines the binding affinity of RTI-4614-4 and its isomers and that the e3 loop also plays a major role in determining the binding affinity of mu agonist peptides. These data also show that the stereoisomers of RTI-4614-4 probably bind to different domains of the mu receptor and suggest that manipulation of stereochemistry may be a useful tool for designing domain-specific ligands. (C) 1998 Wiley-Liss, Inc. C1 NIDA, Clin Psychopharmacol Sect, Div Interamural Res, NIH, Baltimore, MD 21224 USA. Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. Univ Calif San Francisco, Dept Pharm, San Francisco, CA 94143 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Div Interamural Res, NIH, POB 5180,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 41 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 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1998 VL 28 IS 2 BP 117 EP 124 DI 10.1002/(SICI)1098-2396(199802)28:2<117::AID-SYN2>3.0.CO;2-E PG 8 WC Neurosciences SC Neurosciences & Neurology GA YP320 UT WOS:000071265100002 PM 9450512 ER PT J AU Chhabra, RS Herbert, RA Roycroft, JH Chou, B Miller, RA Renne, RA AF Chhabra, RS Herbert, RA Roycroft, JH Chou, B Miller, RA Renne, RA TI Carcinogenesis studies of tetrahydrofuran vapors in rats and mice SO TOXICOLOGICAL SCIENCES LA English DT Article ID CHEMICALS; TOXICITY AB Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for carcinogenesis studies by the National Toxicology Program (NTP) because of its potential for widespread occupational exposure in humans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F(1) mice were exposed to 0, 200, 600, or 1800 ppm THF by inhalation, 6 h per day, 5 days per week, for 105 weeks. Survival and mean body weights of male and female rats exposed to THF were comparable to that of the controls. No clinical findings or nonneoplastic lesions related to THF exposure were observed in male or female rats. The incidences of renal tubule epithelial adenoma or carcinoma (combined) in exposed male rats occurred with a positive trend, and in males exposed to 600 and 1800 ppm exceeded the historical range for controls in 2-year NTP inhalation studies. There were no other neoplastic lesions related to THF exposure observed in male or female rats. After week 36, the survival of male mice exposed to 1800 ppm was significantly lower than that of the controls. Mean body weights of male and female mice exposed to THF were similar to those of the controls throughout the study. Male mice exposed to 1800 ppm were observed in a state of narcosis during and up to 1 h after the exposure periods. Nonneoplastic lesions related to THF exposure were not observed in male or female mice. The neoplastic lesions related to THF exposure were seen in female mice only. In female mice exposed to 1800 ppm, the incidences of hepatocellular neoplasms were significantly greater than those in the controls. In conclusion, there was some evidence of carcinogenic activity of THF in male F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of carcinogenic activity in female B6C3F(1) mice based on increased incidences of hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic in female rats or male mice exposed at 200, 600, or 1800 ppm. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Pacific NW Lab, Richland, WA 99352 USA. RP Chhabra, RS (reprint author), Natl Inst Environm Hlth Sci, POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 16 Z9 16 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 1998 VL 41 IS 2 BP 183 EP 188 DI 10.1093/toxsci/41.2.183 PG 6 WC Toxicology SC Toxicology GA ZM361 UT WOS:000073530800006 PM 9520354 ER PT J AU Wharton, CM Grafman, J AF Wharton, CM Grafman, J TI Deductive reasoning and the brain SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID SELECTION TASK; MENTAL REPRESENTATION; DAMAGE; INFORMATION; SENTENCES; RELEVANCE; THINKING; EXPLAINS; MODELS; RULES AB Although relatively few in number, cognitive neuroscience studies of reasoning have two general implications for cognitive theories of deduction. First, an important distinction among these theories is whether they focus on the effect of personally relevant content on the processes and representations underlying deductive reasoning. Evidence is reviewed indicating that there is a neuroanatomical basis for both content-independent and content-dependent theories of deduction. Clinical and neuroimaging studies appear to show that content-independent reasoning is mediated by the left hemisphere, whereas content-dependent reasoning is mediated by regions in the right hemisphere and the bilateral ventromedial frontal cortex. In normal subjects, reasoning is likely to be based on contributions from both hemispheres. Second, clinical evidence indicates that the visuospatial processes used in deductive reasoning are mediated by the posterior areas of the left hemisphere, and that verbal and visuospatial reasoning representations overlap at the neuroanatomical level. This finding weighs against the claims of mental-model theory that deduction involves a significant nonverbal component. Further investigation, particularly with contemporary neuroimaging methods, is needed to test these preliminary conclusions. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Wharton, CM (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. EM jgr@box-j.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 42 TC 36 Z9 37 U1 3 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD FEB PY 1998 VL 2 IS 2 BP 54 EP 59 DI 10.1016/S1364-6613(98)01122-X PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 171NT UT WOS:000078870700004 PM 21227066 ER PT J AU Strausberg, RL AF Strausberg, RL TI Genetics in profile SO TRENDS IN GENETICS LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Strausberg, RL (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 1998 VL 14 IS 2 BP 50 EP 51 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YZ417 UT WOS:000072252300004 PM 9520596 ER PT J AU Bryant, SD Salvadori, S Cooper, PS Lazarus, LH AF Bryant, SD Salvadori, S Cooper, PS Lazarus, LH TI New delta-opioid antagonists as pharmacological probes SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID RECEPTOR ANTAGONIST; SINGLE-RESIDUE; TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID; MORPHINE-TOLERANCE; HIGH-AFFINITY; BINDING; POTENT; PEPTIDE; MU; SELECTIVITY C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. RP Bryant, SD (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 63 TC 44 Z9 46 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD FEB PY 1998 VL 19 IS 2 BP 42 EP 46 DI 10.1016/S0165-6147(97)01156-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZD503 UT WOS:000072692500002 PM 9550939 ER PT J AU Zhang, QY Clausen, PA Yatsula, BA Calothy, G Blair, DG AF Zhang, QY Clausen, PA Yatsula, BA Calothy, G Blair, DG TI Mutation of polyadenylation signals generates murine retroviruses that produce fused virus-cell RNA transcripts at high frequency SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; REVERSE TRANSCRIPTION; LEUKEMIA-VIRUS; SEQUENCE; DNA; TRANSDUCTION; REPLICATION; MODEL AB Retroviruses act as insertional mutagens and can also capture cellular sequences through a mechanism which initially requires the generation of RNA transcripts which fail to cleave and polyadenylate correctly. The correct termination of retroviral transcripts at the 3' LTR R/U5 junction is primarily dependent on the canonical AAUAAA polyadenylation signal, so we have analyzed the effect of mutating the polyadenylation signal sequences on the properties of a selectable murine retroviral vector. Mutation of consensus polyadenylation signal sequences in the 5' and/or 3' proviral LTRs demonstrated that a UA to CC change generated larger sized virus-specific RNA, consistent with loss of normal polyadenylation. Cell clones infected with viruses generated by proviral constructs containing this mutation in the 5' LTR express either normal-length or elongated viral RNA. Fused transcripts contained the mutant polyadenylation signal, while sequence analysis was consistent with the hypothesis that premature 5' to 3' primer strand transfer was responsible for the high frequency (80%) of wild-type polyadenylation. Cells infected by viruses from constructs mutated in both 5' and 3' proviral LTRs expressed poly(A)(+) viral RNA between 0.3 and 3 kb larger than normal virus in 100% of infected clones, and sequence analysis of clones derived from either infected rodent or human cells confirmed that these transcripts contained both viral and adjacent cellular sequences. While mutant virus exhibits no increased ability to alter cell phenotypes, the read-through transcripts contain both unique and repetitive cell-derived sequences and can easily be recovered using PCR techniques, suggesting that these viruses may serve as effective tools for rapidly cloning cellular sequences and generating random genomic markers for gene mapping. (C) 1998 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Basic Res Lab, Frederick, MD 21702 USA. Inst Curie, CNRS, UMR 146, F-91405 Orsay, France. RP Blair, DG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Basic Res Lab, POB B, Frederick, MD 21702 USA. NR 31 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1998 VL 241 IS 1 BP 80 EP 93 DI 10.1006/viro.1997.8947 PG 14 WC Virology SC Virology GA YV548 UT WOS:000071836100008 PM 9454719 ER PT J AU Rafnar, B Tobin, GJ Nagashima, K Gonda, MA Gunnarsson, E Andresson, OS Georgsson, G Torsteinsdottir, S AF Rafnar, B Tobin, GJ Nagashima, K Gonda, MA Gunnarsson, E Andresson, OS Georgsson, G Torsteinsdottir, S TI Immune response to recombinant visna virus Gag and Env precursor proteins synthesized in insect cells SO VIRUS RESEARCH LA English DT Article DE visna virus; visna virus gag-recombinant; visna virus env-recombinant; baculovirus expression system; visna virus recombinant protein immunization ID ARTHRITIS-ENCEPHALITIS VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN; OLIGOMERIC STRUCTURE; NUCLEOTIDE-SEQUENCE; ANTIBODY-RESPONSE; OVINE LENTIVIRUS; SYSTEM LESIONS; BACULOVIRUS AB Two different recombinant visna virus (VV) gag-baculoviruses were constructed for the expression of precursor VV Gag in insect cells, Both recombinant Gag viruses expressed proteins migrating on SDS-PAGE at the predicted rate for VV Gag precursor, Pr50(gag). However, differences were seen in the morphology of the virus-like particles produced. Monoclonal antibody directed against the VV Gag capsid protein (p25) and sera from sheep infected with ovine lentiviruses reacted to both 50-kDa proteins. A recombinant VV env-baculovirus was constructed, substituting sequences encoding the signal peptide of VV Env with the murine IFN-gamma analogue. Sera from ovine lentivirus infected sheep reacted in immunoblots with two proteins of approximately 100 and 200 kDa found in the plasma membrane of insect cells infected with env-recombinant virus. Sheep immunized with either the recombinant Gag or the Env proteins developed high antibody titers to VV in ELISA. The serum of sheep and ascitic fluid of mice immunized with the recombinant Gag reacted with native Pr50(gag) and the processed Gag proteins in immunoblots, whereas serum of the recombinant Env immunized sheep reacted with VV gp135 and a putative oligomer of gp135. The immunized sheep responded specifically to visna virus by lymphocyte proliferation in vitro. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Iceland, Inst Expt Pathol, IS-112 Reykjavik, Iceland. NCI, Lab Cell & Mol Struct, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Genova Inc, Philadelphia, PA 19101 USA. RP Rafnar, B (reprint author), Univ Iceland, Inst Expt Pathol, IS-112 Reykjavik, Iceland. NR 54 TC 12 Z9 12 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 FEB PY 1998 VL 53 IS 2 BP 107 EP 120 DI 10.1016/S0168-1702(97)00141-X PG 14 WC Virology SC Virology GA ZK870 UT WOS:000073372100001 PM 9620203 ER PT J AU Qiao, GB Han, CL Jiang, RC Sun, CS Wang, Y Wang, YJ AF Qiao, GB Han, CL Jiang, RC Sun, CS Wang, Y Wang, YJ TI Overexpression of P53 and its risk factors in esophageal cancer in urban areas of Xi'an SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GENE; MUTATIONS; FREQUENT AB AIM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi'an and to determine the association between overexpression of P53 and these risk factors. METHODS Ali cases (89) and controls (97) were permanent residents in urban areas of Xi'an, all cases of primary EC had been histologically confirmed, controls were inpatients with non-cancer and nonsmoking-related disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method. RESULTS The smoking and familial history of cancer were significantly associated with EC in Xi'an inhabitants The laboratory assay indicated that P53 positive slain in EC was 50.0% (34/65) and 6.1%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer. CONCLUSION Smoking and familial cancer history were important risk factors for EC, and the alteration of P53 gene may be due to smoking and inheritance factors. C1 Guangzhou Gen Hosp Guangzhou Mil Command, Dept Thorac & Cardiovasc Surg, PLA, Guangzhou 510010, Peoples R China. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Fourth Mil Med Univ, Dept Epidemiol, Xian 710032, Peoples R China. RP Qiao, GB (reprint author), Guangzhou Gen Hosp Guangzhou Mil Command, Dept Thorac & Cardiovasc Surg, PLA, Guangzhou 510010, Peoples R China. NR 13 TC 16 Z9 16 U1 0 U2 0 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD FEB PY 1998 VL 4 IS 1 BP 57 EP 60 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 127AD UT WOS:000076326800021 ER PT J AU Choyke, PL AF Choyke, PL TI From needles to numbers: can noninvasive imaging distinguish benign and malignant adrenal lesions? SO WORLD JOURNAL OF UROLOGY LA English DT Article ID CHEMICAL-SHIFT; ONCOLOGIC PATIENTS; ENHANCED MR; MASSES; CT; BIOPSY; DISTINCTION; ASPIRATION; ADENOMAS; GLAND AB Adrenal masses are a relatively common finding on computed tomography (CT) and magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or clinical follow-up were the only methods of distinguishing benign adenomas from malignancies. On the basis of their higher lipid content, adenomas have characteristic appearances on CT and MRI that can be used to separate them from non-lipid-containing lesions such as metastases. CT densitometry with or without contrast media and chemical shift MRI (CSI) are two examples of techniques with adequate sensitivity (50-90%) and excellent specificity (> 95%) for adrenal adenomas. While the need for invasive tissue sampling is reduced because of these techniques, it is eliminated because lesions not meeting the criteria for adenomas are not always malignant. However, CT densitometry and CSI are likely to reduce significantly the need for histology sampling of incidentally discovered adrenal masses due to the high specificity of these new techniques. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Ctr Clin, Bldg 10,Room 1C660,10 Med Ctr Dr, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 30 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD FEB PY 1998 VL 16 IS 1 BP 29 EP 34 DI 10.1007/s003450050022 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA YY912 UT WOS:000072200400007 PM 9542012 ER PT J AU Hall, FS Huang, S Fong, GF Pert, A AF Hall, FS Huang, S Fong, GF Pert, A TI The effects of social isolation on the forced swim test in Fawn hooded and Wistar rats SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE isolation-rearing; forced swim test; Fawn hooded rats; stress ID SEROTONERGIC FUNCTION; BEHAVIORAL DESPAIR; RESPONSES; CHLOROPHENYLPIPERAZINE; HYPERACTIVITY; IMMOBILITY; DEPRESSION; PREFERENCE AB Although the forced swim test (FST) has long been used as a preclinical screen of antidepressant efficacy, locomotor stimulants are known to produce confounding effects using the traditional dependent measure in this test: immobility. It has recently been suggested that measurement of struggling behavior may be a better index of antidepressant activity. The present experiments examined behavior in the forced swim test in two potential animal models of depression: the Fawn hooded rat, and the isolation-reared rat. No evidence was found to support these assertions, indeed immobility was decreased in Fawn hooded compared to Wistar rats, however this appeared to be caused by increased struggling behavior in Fawn hooded socials and increased swimming in Fawn hooded isolates. Although these differential results are highly suggestive of different underlying causes of decreased immobility in Fawn hooded rats depending on rearing conditions, the data suggests that the underlying psychological functions assumed to be represented by behavior assessed in this paradigm may not be adequately discriminated. (C) 1998 Elsevier Science B.V. C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Hall, FS (reprint author), NIAAA, Clin Studies Lab, 10-3C207,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 18 TC 37 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 31 PY 1998 VL 79 IS 1 BP 47 EP 51 DI 10.1016/S0165-0270(97)00155-6 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZC976 UT WOS:000072638100007 PM 9531459 ER PT J AU Linde, K Jonas, WB AF Linde, K Jonas, WB TI Meta-analysis of homeopathy trials - Reply SO LANCET LA English DT Letter C1 Tech Univ Munich, Munchener Modell Ctr Complementary Med Res, D-80801 Munich, Germany. Natl Inst Hlth, Off Alternat Med, Bethesda, MD USA. RP Linde, K (reprint author), Tech Univ Munich, Munchener Modell Ctr Complementary Med Res, D-80801 Munich, Germany. NR 4 TC 3 Z9 3 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 31 PY 1998 VL 351 IS 9099 BP 367 EP 368 DI 10.1016/S0140-6736(05)78307-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YV794 UT WOS:000071864000052 ER PT J AU Hsing, AW Gao, YT Devesa, SS Jin, F Fraumeni, JF AF Hsing, AW Gao, YT Devesa, SS Jin, F Fraumeni, JF TI Rising incidence of biliary tract cancers in Shanghai, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GALLBLADDER CANCER; GALLSTONES; TRENDS; RISK AB Cancers of the biliary tract, including cancers of the gallbladder, extra-hepatic bile ducts, and ampulla of Vater, are relatively uncommon malignancies. From 1972 to 1994, biliary tract cancer was the most rapidly rising malignancy in Shanghai, China, with a 119% increase in men and 124% in women. The increase in incidence was seen for all 3 subsites, both sexes, and all age groups. Future studies are needed to identify reasons for the large increases in these rates. (C) 1998 Wiley-Liss, Inc.(dagger) C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPN 443,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 15 TC 52 Z9 63 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 30 PY 1998 VL 75 IS 3 BP 368 EP 370 DI 10.1002/(SICI)1097-0215(19980130)75:3<368::AID-IJC7>3.0.CO;2-0 PG 3 WC Oncology SC Oncology GA YU408 UT WOS:000071714100007 PM 9455795 ER PT J AU Wang, J Yang, WK Yang, YL Wei, SJ Yang, DM Whang-Peng, J Chen, YM Ting, KL Ting, CC AF Wang, J Yang, WK Yang, YL Wei, SJ Yang, DM Whang-Peng, J Chen, YM Ting, KL Ting, CC TI Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; LASTING ANTITUMOR IMMUNITY; CELLS; POTENT; SUPPRESSION; MELANOMA; INVIVO AB The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined, Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh), The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity, However, the proliferation of the NG-MGh cells was increased 2- to 10-fold, There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells, Mixing the splenocytes from the NG-MGh tumor beavers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s), Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site. (C) 1998 Wiley-Liss, Inc.dagger C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. Vet Gen Hosp, Cooperat Canc Clin Res Lab, Natl Hlth Res Inst, Taipei, Taiwan. Acad Sinica, Taipei 115, Taiwan. RP Ting, CC (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 10,Room 4B17, Bethesda, MD 20892 USA. NR 21 TC 7 Z9 7 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 30 PY 1998 VL 75 IS 3 BP 459 EP 466 PG 8 WC Oncology SC Oncology GA YU408 UT WOS:000071714100021 PM 9455809 ER PT J AU Lopez-Ilasaca, M Gutkind, JS Wetzker, R AF Lopez-Ilasaca, M Gutkind, JS Wetzker, R TI Phosphoinositide 3-kinase gamma is a mediator of G beta gamma-dependent Jun kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SIGNALING PATHWAY; SUBUNITS; CDC42; RAS AB Jun kinases (JNK) are involved in the stress response of mammalian cells, Stimulation of JNK can be induced by stress factors and by agonists of tyrosine kinase and G protein coupled receptors, G protein-dependent receptors stimulate JNK via G beta gamma subunits of heterotrimeric G proteins, but the subsequent signaling reaction has been undefined. Here we demonstrate JNK activation in COS-7 cells by G beta gamma-stimulated phosphoinositide S-kinase gamma (PI3K gamma). Signal transduction from PI3K gamma to JNK can be suppressed by dominant negative mutants of Ras, Rac, and the protein kinase PAK. These results identify PI3K gamma as a mediator of G beta gamma-dependent regulation of JNK activity. C1 Univ Jena, Fac Med, Max Planck Res Unit Mol Cell Biol, D-07747 Jena, Germany. NIH, Mol Signaling Unit, Cellular Dev & Oncol Lab, NIDR, Bethesda, MD 20892 USA. RP Wetzker, R (reprint author), Univ Jena, Fac Med, Max Planck Res Unit Mol Cell Biol, Drackendorfer Str 1, D-07747 Jena, Germany. EM i5rewe@rz.uni-jena.de RI Gutkind, J. Silvio/A-1053-2009 NR 16 TC 85 Z9 85 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 JAN 30 PY 1998 VL 273 IS 5 BP 2505 EP 2508 DI 10.1074/jbc.273.5.2505 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600005 PM 9446550 ER PT J AU Song, Y Withers, DA Hakomori, S AF Song, Y Withers, DA Hakomori, S TI Globoside-dependent adhesion of human embryonal carcinoma cells, based on carbohydrate-carbohydrate interaction, initiates signal transduction and induces enhanced activity of transcription factors AP1 and CREB SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID-INDUCED DIFFERENTIATION; HUMAN TERATOCARCINOMA CELLS; NF-KAPPA-B; MONOCLONAL-ANTIBODY; PREIMPLANTATION EMBRYOS; MOUSE EMBRYOS; GLYCOSPHINGOLIPIDS; EXPRESSION; ANTIGEN; PROTEIN AB Undifferentiated human embryonal carcinoma cells are characterized by high expression of lactoneotetraosylceramide (nLc(4)), globoside (Gb4), and extended globe-series glycosphingolipids (GSLs) termed "stage-specific embryonic antigens 3 and 4" (SSEA-3 and -4), Expression of these GSLs declines in association with a decline of homotypic adhesion during the differentiation process, Therefore, these GSLs may play an essential role in adhesion among these cells, As an example, human embryonal carcinoma 2102 cells display strong adhesion to plates coated with Gb4 ("Gb4-dependent cell adhesion"), This adhesion, which simulates homotypic 2102 cell aggregation, is based on interaction between Gb4 and nLc(4), or between Gb4 and GalGb4 (IV(3)GalGb4; the major SSEA-3 epitope), as indicated by the following observations: (i) adhesion of 2102 cells or GSL-liposomes to GSL-coated plates in various combinations; (ii) inhibition of Gb4-dependent 2102 cell adhesion by preincubation of cells with anti-SSEA-3 or anti-nLc(4) antibodies, or by pretreatment of Gb4-coated plates with aqueous micellar solution of nLc(4) or GalGb4; (iii) decline of the cell adhesion in association with retinoic acid-induced differentiation, whereby SSEA-3 and nLc(4) levels are reduced, Since cell adhesion is an essential prerequisite for induction of differentiation, as observed at each step of embryogenesis, expression of seven transcription fac tors following adhesion of 2102 cells to Gb4-coated plates, and to detergent-insoluble substrate adhesion matrix prepared from 2102 cells, were studied, In both types of adhesion, a strong enhancement of AP1 and CREB site binding activity was observed during the early stage (15-60 min following initial adhesion), Although 2102 cells showed strong adhesion to Gg3-coated plates, based on interaction between Gg3 and Gb4, adhesion of the cells to Gg3 did not cause changes of AP1 and CREB activity, No other transcription factors showed changes induced by Gg3- or Gb4-dependent adhesion. C1 Pacific NW Res Fdn, Seattle, WA 98122 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Song, Y (reprint author), NIDDK, Lab Cell Biochem, NIH, MSC 0850,Bldg 8,Rm 402, Bethesda, MD 20892 USA. RI Auzanneau, France-Isabelle/E-9153-2010 FU NCI NIH HHS [CA42505] NR 56 TC 49 Z9 49 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 JAN 30 PY 1998 VL 273 IS 5 BP 2517 EP 2525 DI 10.1074/jbc.273.5.2517 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600007 PM 9446552 ER PT J AU Vitale, N Moss, J Vaughan, M AF Vitale, N Moss, J Vaughan, M TI Molecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEIN; BINDING-PROTEIN; CHOLERA-TOXIN; CRYSTAL-STRUCTURE; PHOSPHOLIPASE-D; ACID PHOSPHOLIPIDS; CHROMAFFIN CELLS; GOLGI MEMBRANES; ALPHA-SUBUNIT; FACTOR-I AB ADP-ribosylation factors (ARFs) are similar to 20-kDa guanine nucleotide-binding proteins recognized as critical components in intracellular vesicular transport and phospholipase D activation, Both guanine nucleotide-exchange proteins and GTPase-activating proteins (GAPs) for ARFs have been cloned recently. A zinc finger motif near the amino terminus of the ARF1 GAP was required for stimulation of GTP hydrolysis. ARD1 is an ARF family member that differs from other ARFs by the presence of a 46-kDa amino-terminal extension, We had reported that the ARF domain of ARD1 binds specifically GDP and GTP and that the amino-terminal extension acts as a GAP for the ARF domain of ARD1 but not for ARF proteins, The GAP domain of ARD1, synthesized in Escherichia coli, stimulated hydrolysis of GTP bound to the ARF domain of ARD1, Using ARD1 truncations, it appears that amino acids 101-190 are critical for GAP activity, whereas residues 190-333 are involved in physical interaction between the two domains of ARD1 and are required for GTP hydrolysis. The GAP function of the amino-terminal extension of ARD1 required two arginines, an intact zinc finger motif, and a group of residues which resembles a sequence present in Rho/Pac GAPs, Interaction between the two domains of ARD1 required two negatively charged residues (Asp(427) and Glu(428)) located in the effector region of the ARF domain and two basic amino acids (Arg(249) and Lys(250)) found in the amino-terminal extension, The GAP domain of ARD1 thus is similar to ARF GAPs but differs from other GAPs in its covalent association with the GTP-binding domain. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vitale, N (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Room 5N-307,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. EM vitalen@fido.nhlbi.nih.gov RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 55 TC 23 Z9 25 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 JAN 30 PY 1998 VL 273 IS 5 BP 2553 EP 2560 DI 10.1074/jbc.273.5.2553 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600011 PM 9446556 ER PT J AU Wang, J Villeneuve, S Zhang, J Lei, PS Miller, CE Lafaye, P Nato, F Szu, SSC Karpas, A Bystricky, S Robbins, JB Kovac, P Fournier, JM Glaudemans, CPJ AF Wang, J Villeneuve, S Zhang, J Lei, PS Miller, CE Lafaye, P Nato, F Szu, SSC Karpas, A Bystricky, S Robbins, JB Kovac, P Fournier, JM Glaudemans, CPJ TI On the antigenic determinants of the lipopolysaccharides of Vibrio cholerae O : 1, serotypes Ogawa and Inaba SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHYL ALPHA-GLYCOSIDE; MONOSACCHARIDE REPEATING UNIT; O-POLYSACCHARIDE; STRUCTURAL-ANALYSIS; IMMUNOGLOBULIN-A; CORE REGION; O139; ANTIBODIES; BINDING; O/1 AB Monoclonal, murine IgG(1)s S-20-4, A-20-6, and IgA 2D6, directed against Vibrio cholerae O:1 Ogawa-lipopolysaccharide exhibited the same fine specificities and similar affinities for the synthetic methyl a glycosides of the (oligo)saccharide fragments mimicking the Ogawa O-polysaccharide (O-PS). They did not react with the corresponding synthetic fragments of Inaba O-PS. IgG(1)s S-20-4 and A-20-6 have absolute affinity constants for synthetic Ogawa mono-to hexasaccharides of from similar to 10(5) to similar to 10(6) M-1. For IgG(1)s S-20-4, A-20-6, and IgA 2D6, the nonreducing terminal residue of Ogawa O-PS is the dominant determinant, accounting for similar to 90% of the maximal binding energy shown by these antibodies. finding studies of derivatives of the Ogawa monosaccharide and IgGs S-20-4 and A-20-6 revealed that the C-2 O-methyl group fits into a somewhat flexible antibody cavity and that hydrogen bonds involving the oxygen and, respectively, the OH at the 2- and 3-position of the sugar moiety as well as the 2'-position in the amide side chain are required. Monoclonal IgA ZAC-3 and IgG(3) I-24-2 are specific for V. cholerae O:1 serotypes Ogawa/lnaba-LPS.(1) The former did not show binding with members of either series of the synthetic ligands related to the O-antigens of the Ogawa or Inaba serotypes, in agreement with its reported specificity for the lipid/core region (1). Inhibition studies revealed that the binding of purified IgG, I-24-2 to Ogawa-LPS might be mediated by a region in the junction of the OPS to the lipid-core region of the LPS. cDNA cloning and analysis of the anti-Ogawa antibodies S-20-4, A-20-6, and 2D6 revealed a very high degree of homology among the heavy chains. Among the light chains, no such homology between S-20-4 and A-20-6 on the one hand, and 2D6 on the other hand, exists. For the anti-Inaba/Ogawa antibodies I-24-2 and ZAC-3, their heavy chains are completely different, with some homology among the light chains. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. Ctr Natl Reference Vibr & Cholera, Unite Cholera & Bivr, F-75724 Paris, France. Inst Pasteur, Hybridolab, F-75724 Paris 15, France. RP Glaudemans, CPJ (reprint author), NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. EM glau@helix.nih.gov NR 35 TC 54 Z9 54 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 JAN 30 PY 1998 VL 273 IS 5 BP 2777 EP 2783 DI 10.1074/jbc.273.5.2777 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600040 PM 9446585 ER PT J AU Sakatsume, M Stancato, LF David, M Silvennoinen, O Saharinen, P Pierce, J Larner, AC Finbloom, DS AF Sakatsume, M Stancato, LF David, M Silvennoinen, O Saharinen, P Pierce, J Larner, AC Finbloom, DS TI Interferon gamma activation of Raf-1 is Jak1-dependent and p21(ras)-independent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASE; SERINE THREONINE KINASE; PROTEIN-TYROSINE KINASE; GENE-EXPRESSION; HUMAN-MONOCYTES; CELL-LINES; RECEPTOR; PHOSPHORYLATION; RAS; BINDING AB Signal transduction through the interferon gamma (IFN gamma) receptor involves the formation of a ligand-dependent multimolecular association of receptor chains (alpha and beta), Janus tyrosine kinases (Jak1 and Jak2), and the transcription factor (signal transducers and activators of transcription 1 alpha (STAT1 alpha)) in addition to activation of mitogen-activated protein kinases (MAPK), Interactions between components of the Jak/STAT cascade and the p21(ras)/Raf-1/MAPK cascade are unexplored, Treatment of HeLa cells with IFN gamma resulted in the rapid and transient activation of Raf-1 and MAPK. Parallel activation of cells resulted in essentially no enhancement of p21(ras) activation despite marked enhancement after treatment with epidermal growth factor, In HeLa (E1C3) and fibrosarcoma (U4A) cell lines, both of which are deficient in Jak1 kinase, Raf-1 activation by IFN gamma was absent. Reconstitution of Raf-1 activity was observed only with kinase active Jak1 in both cell lines. In COS cells, transient expression of wild type or kinase-inactive Jak1 coimmunoprecipitated with Raf-1, but activation of Raf-1 activity was only observed in cells expressing kinase-active Jak1. These observations suggest that a kinase-active Jak1 is required for IFN gamma activation of Raf-1 that is p21(ras)-independent. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. RP Finbloom, DS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-505,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Finbloom@A1.cbef.fda.gov RI Saharinen, Pipsa/C-9601-2016 OI Saharinen, Pipsa/0000-0003-2652-0584 NR 41 TC 67 Z9 69 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 JAN 30 PY 1998 VL 273 IS 5 BP 3021 EP 3026 DI 10.1074/jbc.273.5.3021 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600071 PM 9446616 ER PT J AU De Angelis, J Gastel, J Klein, DC Cole, PA AF De Angelis, J Gastel, J Klein, DC Cole, PA TI Kinetic analysis of the catalytic mechanism of serotonin N-acetyltransferase (EC 2.3.1.87) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACETYL-ENZYME INTERMEDIATE; PINEAL-GLAND; ESCHERICHIA-COLI; COENZYME-A; EXPRESSION; RHYTHM; SITE; RAT AB Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT, EC 2.3.1.87) is the penultimate enzyme in melatonin biosynthesis. This enzyme is of special biological interest because large changes in its activity drive the large night/day rhythm in circulating melatonin in vertebrates, In this study the kinetic mechanism of AANAT action was studied using bacterially expressed glutathione S-transferase (GST)-AANAT fusion protein, The enzymologic behavior of GST-AANAT and cleaved AANAT was essentially identical, Two-substrate kinetic analysis generated an intersecting line pattern characteristic of a ternary complex mechanism, The dead end inhibitor analog desulfo-CoA was competitive versus acetyl-CoA and noncompetitive versus tryptamine. Tryptophol was not an alternative substrate but was a dead end competitive inhibitor versus tryptamine and an uncompetitive inhibitor versus acetyl-CoA, indicative of an ordered binding mechanism requiring binding of acetyl-CoA first, N-Acetyl-tryptamine, a reaction product, was a noncompetitive inhibitor versus tryptamine and uncompetitive with respect to acetyl-CoA, Taken together these results support an ordered BiBi ternary complex (sequential) kinetic mechanism for AANAT and provide a framework for inhibitor design. C1 Rockefeller Univ, Bioorgan Chem Lab, New York, NY 10021 USA. NICHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Cole, PA (reprint author), Rockefeller Univ, Bioorgan Chem Lab, 1230 York Ave, New York, NY 10021 USA. NR 32 TC 92 Z9 92 U1 0 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 JAN 30 PY 1998 VL 273 IS 5 BP 3045 EP 3050 DI 10.1074/jbc.273.5.3045 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600075 PM 9446620 ER PT J AU Gee, P Sommers, CH Melick, AS Gidrol, XM Todd, MD Burris, RB Nelson, ME Klemm, RC Zeiger, E AF Gee, P Sommers, CH Melick, AS Gidrol, XM Todd, MD Burris, RB Nelson, ME Klemm, RC Zeiger, E TI Comparison of responses of base-specific Salmonella tester strains with the traditional strains for identifying mutagens, the results of a validation study SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella mutagenicity test; validation study; fluctuation test; high throughput screening; Ames II ID MOUSE MUTATION ASSAY; FLUCTUATION TEST; ESCHERICHIA-COLI; AMES-TEST; CHEMICALS; TYPHIMURIUM; CARCINOGENICITY; REPRODUCIBILITY; ACETONITRILES; MIXTURES AB The ability of a TA7000 series of Salmonella his(-) mutant tester strains to detect mutagens as classified by the traditional tester strains (TA100, TA98, TA1535, TA1537, TA97, TA102 and TA104) was evaluated using 30 coded chemicals, 5 of which were duplicates with different code numbers. The TA7000 series of tester strains were TA7001, TA7002, TA7003, TA7004, TA7005 and TA7006, each of which reverts by a specific base substitution. In addition, each chemical was tested in a mixture of the base-specific strains (the Mix), plus the traditional strains, TA98 and TA1537. A liquid version of the Salmonella mutagenicity assay was performed in microtiter plates to allow partial automation for increased throughput. The results were compared to those in the National Toxicology Program (NTP) database, which were obtained from the traditional strains in the preincubation assay. In the two strains common to both protocols, TA98 and TA1537, the agreement was 80% and 85%, respectively. When compared to the NTP results for TA100, the Mix gave a 72% concordance, while the addition of the frameshift tester strain, TA98, increased the agreement to 76%. The overall agreement on positive or negative classifications of mutagenicity was 88% for the 25 chemicals tested. There were three notable exceptions to the overall agreement. Benzaldehyde was detected as a mutagen in TA7005 in contrast to its classification as a non-mutagen in the NTP database. This does not necessarily contradict the NTP results because the base-specific strains may respond to different mutagens. Two weak mutagens in the NTP database, 1-chloro-2-propanol and isobutyl nitrite, were not detected as mutagens in the base-specific new strains in the liquid protocol. While there are a number of major differences in the two assays, it was concluded that the results from each procedure are comparable. (C) 1998 Elsevier Science B.V. C1 Xenometrix Inc, Boulder, CO 80301 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Gee, P (reprint author), Xenometrix Inc, 2425 N 55th St, Boulder, CO 80301 USA. NR 47 TC 44 Z9 45 U1 4 U2 13 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 JAN 30 PY 1998 VL 412 IS 2 BP 115 EP 130 DI 10.1016/S1383-5718(97)00172-1 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZD067 UT WOS:000072647900002 PM 9539966 ER PT J AU Smith, CS Wyatt, RJ Masserano, JM AF Smith, CS Wyatt, RJ Masserano, JM TI Nitric oxide induces cell death in a catecholaminergic cell line derived from the central nervous system SO NEUROSCIENCE LETTERS LA English DT Article DE nitric oxide; dopamine; cell death; mitochondria; sodium nitroprusside; rhodamine-123 ID METHYL-D-ASPARTATE; DOPAMINE UPTAKE; H-3 DOPAMINE; PEROXYNITRITE; NEUROTOXICITY; SUPEROXIDE; INHIBITION; APOPTOSIS; CULTURES; SLICES AB The nitric oxide (NO) donors, sodium nitroprusside (SNP), 1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2- diolate] (DETA NONOate), and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) produce a dose-dependent increase in cell death in a catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death is associated with a decrease in mitochondrial membrane potential. Dopamine also induced cell death of CATH.a cells and this was potentiated by concentrations of SNP which alone did not produce cell death. Hemoglobin, a scavenger of NO radicals, blocked SNP-and SNAP-induced cell death. Catalase and superoxide dismutase, enzymes that metabolize H2O2 and superoxide, respectively, did not inhibit SNP- or SNAP-induced cell death. These data indicate that NC) donors produce cell death in CATH.a cells through a mechanism related to the production of NO and the loss of the mitochondrial membrane potential but unrelated to the production of H2O2. (C) 1998 Published by Elsevier Science Ireland Ltd. C1 NIMH, Neurosci Ctr St Elizabeths, Neuropsychiat Branch, Washington, DC 20032 USA. RP Masserano, JM (reprint author), NIMH, Neurosci Ctr St Elizabeths, Neuropsychiat Branch, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. NR 20 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 30 PY 1998 VL 241 IS 2-3 BP 71 EP 74 DI 10.1016/S0304-3940(97)00961-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YX668 UT WOS:000072064500001 PM 9507923 ER PT J AU Sei, Y Fossom, L Goping, G Skolnick, P Basile, AS AF Sei, Y Fossom, L Goping, G Skolnick, P Basile, AS TI Quinolinic acid protects rat cerebellar granule cells from glutamate-induced apoptosis SO NEUROSCIENCE LETTERS LA English DT Article DE apoptosis; cell death; glutamate; granule neuron; neurotoxicity; quinolinic acid ID D-ASPARTATE PROMOTES; NMDA RECEPTORS; LR WHITE; CULTURE; NEURONS; DEATH; NEUROTOXICITY; ACTIVATION; SURVIVAL; EXPOSURE AB The effects of quinolinic acid (QUIN) on glutamate-induced excitotoxicity were examined in primary cultures of rat cerebellar granule neurons. Exposing these neurons to QUIN (less than or equal to 2.5 mM) in the presence of glucose and Mg2+ had no effect on their viability. Although pretreating neurons with QUIN (10 mu M) for 6 h did not reduce necrotic death induced by glutamate exposure in the absence of glucose and Mg2+, QUIN pretreatment significantly suppressed glutamate-induced apoptosis by 68% (as indicated by DNA fragmentation) in cultures containing glucose and Mg2+. Furthermore, the M-methyl-D-aspartate (NMDA) receptor antagonist AP-5 reversed QUIN-induced neuroprotection, while the non-NMDA antagonist CNQX had no effect. This study demonstrates that pathophysiologically relevant concentrations of QUIN can protect neurons from apoptosis mediated via the NMDA receptor. (C) 1998 Elsevier Science Ireland Ltd. C1 Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA. NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Sei, Y (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM Ysei@mx3.usuhs.mil NR 24 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 30 PY 1998 VL 241 IS 2-3 BP 180 EP 184 DI 10.1016/S0304-3940(97)00980-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA YX668 UT WOS:000072064500028 PM 9507950 ER PT J AU Karon, JM Khare, M Rosenberg, PS AF Karon, JM Khare, M Rosenberg, PS TI The current status of methods for estimating the prevalence of human immunodeficiency virus in the United States of America SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Centers-for-Disease-Control Workshop on AIDS Case Projections and HIV Seroprevalence and Incidence Estimates CY FEB, 1995 CL ATLANTA, GEORGIA SP Ctr Dis Control ID HIV-INFECTION; AIDS EPIDEMIC; DRUG-USERS; TRENDS; DISEASE; SEROPREVALENCE; RATES; WOMEN; BACKCALCULATION; PROJECTIONS AB The prevalence of human immunodeficiency virus (HIV) infection can be estimated by two distinct methods, One method, back-calculation, is a complex statistical procedure that estimates the HIV epidemic curve. The second method is based on data from population-based surveys, which provide estimates of the proportion of persons infected with HIV within subgroups, and on the known or estimated population totals for these subgroups. Estimates from these methods are subject to substantial uncertainty and bias, both of which are difficult to quantify. We review recent use of these procedures to estimate HIV prevalence in the United States of America, We also summarize new data on the uncertainty and the bias in these estimates. Reliable estimates of HIV prevalence can be made only by synthesizing estimates from several procedures and by a comprehensive evaluation of relevant data. Future estimates of HIV prevalence will require modifications of these methods or the development of new methods, (C) 1998 John Wiley & Sons, Ltd. C1 Ctr Dis Control & Prevent, Div HIV AIDS Prevent Surveillance & Epidemiol E48, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Div Hlth Examinat Stat, Natl Ctr Hlth Stat, Hyattsville, MD USA. NCI, Epidemiol & Biostat Program, Epidemiol Methods Sect, Rockville, MD USA. RP Karon, JM (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent Surveillance & Epidemiol E48, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. NR 45 TC 14 Z9 15 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1998 VL 17 IS 2 BP 127 EP 142 DI 10.1002/(SICI)1097-0258(19980130)17:2<127::AID-SIM756>3.0.CO;2-R PG 16 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 YW314 UT WOS:000071921500002 PM 9483724 ER PT J AU Rosenberg, PS Goedert, JJ AF Rosenberg, PS Goedert, JJ TI Estimating the cumulative incidence of HIV infection among persons with haemophilia in the United States of America SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Centers-for-Disease-Control Workshop on AIDS Case Projections and HIV Seroprevalence and Incidence Estimates CY FEB, 1995 CL ATLANTA, GEORGIA SP Ctr Dis Control ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS; PREVALENCE; MORTALITY; EPIDEMIC AB We used complementary approaches to estimate the cumulative incidence of infection with the human immunodeficiency virus (HIV) among persons with haemophilia in the United States of America. One approach, ratio estimation, divided the cumulative number of haemophiliacs diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States by the corresponding cumulative proportion with AIDS among HIV-positive subjects in the Multicenter Hemophilia Cohort Study (MHCS). The other approach, back-calculation, reconstructed past HIV incidence from national surveillance of AIDS using essentially non-parametric estimates of the hazard functions for AIDS and for pre-AIDS death. We derived confidence intervals that fully incorporated uncertainty about the hazard functions. Results from the two approaches were consistent. Around 9200 haemophiliacs became infected during the course of the epidemic. Of them, around 7000 were living with HIV or AIDS as of 31 December 1992 and at least 5630 as of 31 December 1995. Credible calculations for this group must account for those who die before AIDS and for the significantly longer incubation times in those infected as children or adolescents. The consistency of back-calculation and cohort data in haemophiliacs supports the use of back-calculation to estimate prevalence in other populations. (C) 1998 John Wiley & Sons, Ltd. C1 NCI, Rockville, MD 20852 USA. RP Rosenberg, PS (reprint author), NCI, 6130 Execut Blvd,EPN-403, Rockville, MD 20852 USA. NR 22 TC 7 Z9 7 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1998 VL 17 IS 2 BP 155 EP 168 DI 10.1002/(SICI)1097-0258(19980130)17:2<155::AID-SIM758>3.0.CO;2-O PG 14 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 YW314 UT WOS:000071921500004 PM 9483726 ER PT J AU Parascandola, M AF Parascandola, M TI The progress of experiment - Science and therapeutic reform in the United-States, 1900-1990 SO TLS-THE TIMES LITERARY SUPPLEMENT LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TIMES SUPPLEMENTS LIMITED PI MARKET HARBOROUGH PA TOWER HOUSE, SOVEREIGN PARK, MARKET HARBOROUGH LE87 4JJ, ENGLAND SN 0307-661X J9 TLS-TIMES LIT SUPPL JI TLS-Times Lit. Suppl. PD JAN 30 PY 1998 IS 4948 BP 9 EP 9 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA YV084 UT WOS:000071788000009 ER PT J AU Parascandola, M AF Parascandola, M TI Hazards of the job - From industrial disease to environmental health science SO TLS-THE TIMES LITERARY SUPPLEMENT LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TIMES SUPPLEMENTS LIMITED PI MARKET HARBOROUGH PA TOWER HOUSE, SOVEREIGN PARK, MARKET HARBOROUGH LE87 4JJ, ENGLAND SN 0307-661X J9 TLS-TIMES LIT SUPPL JI TLS-Times Lit. Suppl. PD JAN 30 PY 1998 IS 4948 BP 9 EP 9 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA YV084 UT WOS:000071788000008 ER PT J AU Gottlieb, JP Kusunoki, M Goldberg, ME AF Gottlieb, JP Kusunoki, M Goldberg, ME TI The representation of visual salience in monkey parietal cortex SO NATURE LA English DT Article ID LATERAL INTRAPARIETAL AREA; EYE-MOVEMENTS; MACAQUE; FIELD; ORGANIZATION AB When natural scenes are viewed, a multitude of objects that are stable in their environments are brought in and out of view by eye movements. The posterior parietal cortex is crucial for the analysis of space, visual attention and movement(1). Neurons in one of its subdivisions, the lateral intraparietal area (LIP), have visual responses to stimuli appearing abruptly at particular retinal locations (their receptive fields)(2). We have rested the responses of LIP neurons to stimuli that entered their receptive field by saccades. Neurons had little or no response to stimuli brought into their receptive field by saccades, unless the stimuli were behaviourally significant. We established behavioural significance in two ways: either by making a stable stimulus task-relevant, or by taking advantage of the attentional attraction of an abruptly appearing stimulus. Our results show that under ordinary circumstances the entire visual world is only weakly represented in LIP. The visual representation in LIP is sparse, with only the most salient or behaviourally relevant objects being strongly represented. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. RP Goldberg, ME (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 670 Z9 678 U1 1 U2 28 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 29 PY 1998 VL 391 IS 6666 BP 481 EP 484 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YU290 UT WOS:000071701800049 PM 9461214 ER PT J AU Puck, JM Willard, HF AF Puck, JM Willard, HF TI X inactivation in females with X-linked disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP Puck, JM (reprint author), NIH, Bethesda, MD 20892 USA. NR 11 TC 128 Z9 130 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 1998 VL 338 IS 5 BP 325 EP 328 DI 10.1056/NEJM199801293380611 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YT963 UT WOS:000071665200011 PM 9445416 ER PT J AU Ioannidis, JPA AF Ioannidis, JPA TI Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; CLINICAL-TRIALS; CUBIC MILLIMETER; HIV-INFECTION; DOUBLE-BLIND; BIAS; METAANALYSIS; AIDS; ZIDOVUDINE; DISEASE AB Context.-Medical evidence may be biased over time if completion and publication of randomized efficacy trials are delayed when results are not statistically significant. Objective.-To evaluate whether the time to completion and the time to publication of randomized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials. Design.-Prospective cohort of randomized efficacy trials conducted by 2 trialist groups from 1986 to 1996. Setting.-Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health. Patients.-A total of 109 efficacy trials (total enrollment, 43 708 patients). Main Outcome Measures.-Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer-reviewed publication assessed with survival analysis. Results.-The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm (6.5 vs 4.3 years, respectively; P<.001; hazard ratio for time to publication for positive vs negative trials, 3.7; 95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable to differences in the time from completion to publication (median, 3.0 vs 1.7 years for negative vs positive trials; P<.001). On average, trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5 years; P=.045), but long-protracted trials often had low event rates and failed to reach statistical significance, while trials that were terminated early had significant results. Positive trials were submitted for publication significantly more rapidly after completion than were negative trials (median, 1.0 vs 1.6 years; P=.001) and were published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04). Conclusion.-Among randomized efficacy trials, there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up. C1 NIAID, HIV Res Branch, Therapeut Res Program, Div Aids,NIH, Bethesda, MD 20892 USA. RP Ioannidis, JPA (reprint author), NIAID, HIV Res Branch, Therapeut Res Program, Div Aids,NIH, Solar Bldg 2C31,6003 Execut Blvd, Bethesda, MD 20892 USA. EM ji24m@nih.gov RI Ioannidis, John/G-9836-2011 NR 30 TC 329 Z9 332 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 28 PY 1998 VL 279 IS 4 BP 281 EP 286 DI 10.1001/jama.279.4.281 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YT472 UT WOS:000071607000034 PM 9450711 ER PT J AU Strickler, HD Rosenberg, PS Devesa, SS Hertel, J Fraumeni, JF Goedert, JJ AF Strickler, HD Rosenberg, PS Devesa, SS Hertel, J Fraumeni, JF Goedert, JJ TI Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN BRAIN-TUMORS; CHOROID-PLEXUS; DNA-SEQUENCES; SV40 AB Context.-Poliovirus vaccine contaminated with live simian virus 40 (SV40), a polyomavirus that is tumorigenic in rodents, was used extensively in the United States between 1955 and 1963, Simian virus 40 DNA has recently been detected in several rare human tumors, including ependymomas, osteosarcomas. mesotheliomas. Objective.-To determine the risk of ependymoma, osteosarcoma, and mesothelioma among Americans who as children received SV40-contaminated poliovirus vaccine. Design.-Retrospective cohort study using data from the Surveillance, Epidemiology, and End Results program (1973-1993) and the Connecticut Tumor Registry (1950-1969), as well as national mortality statistics (1947-1973). Setting.-United States. Participants.-Birth cohorts that were likely to have received SV40-contaminated poliovirus vaccine as infants, born 1956 through 1962 (60 811 730 person-years of observation); as children, born 1947 through 1952 (46 430 953 person-years); or that were unexposed, born 1964 through 1969 (44 959 979 peron-years). Main Outcome Measures.-Relative risk (RR) of each cancer among exposed compared with unexposed birth cohorts. Results.-Age-specific cancer rates were generally low and were not significantly elevated in birth cohorts exposed to SV40-contaminated vaccine, Specifically, compared with the unexposed, the relative risk of ependymoma was not increased in the cohorts exposed as infants (RR, 1.06; 95% confidence interval [CI], 0.69-1.63), or as children (RR, 0.98; 95% CI, 0.57-1.69) nor did the exposed have an increased risk of all brain cancers. Osteosarcoma incidence also showed no relation to exposure as infants (RR, 0.87; 95% CI, 0.71-1.06) or children (RR, 0.85; 95% CI, 0.59-1.22). Last, mesotheliomas were not significantly associated with exposure, although the cohorts studied have not. yet reached the age at which these tumors tend to occur. Conclusions.-After more than 30 years of follow-up, exposure to SV40-contaminated poliovirus vaccine was not associated with significantly increased rates of ependymomas and other brain cancers, osteosarcomas, or mesotheliomas in the United States. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Informat Management Syst, Rockville, MD USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6130 Execut Blvd,EPN Room 434, Rockville, MD 20852 USA. NR 21 TC 120 Z9 123 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 28 PY 1998 VL 279 IS 4 BP 292 EP 295 DI 10.1001/jama.279.4.292 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YT472 UT WOS:000071607000036 PM 9450713 ER PT J AU O'Brien, TR Goedert, JJ AF O'Brien, TR Goedert, JJ TI Chemokine receptors and genetic variability - Another leap in HIV research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INFECTION; AIDS; IDENTIFICATION; MIP-1-ALPHA; INDIVIDUALS; PROGRESSION; MIP-1-BETA; CORECEPTOR; RESISTANCE; COFACTOR C1 NCI, Viral Epidemiol Branch, US Publ Hlth Serv, US Dept HHS, N Bethesda, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, US Publ Hlth Serv, US Dept HHS, N Bethesda, MD 20852 USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, US Publ Hlth Serv, US Dept HHS, EPN 434,6130 Execut Blvd, N Bethesda, MD 20852 USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 28 PY 1998 VL 279 IS 4 BP 317 EP 318 DI 10.1001/jama.279.4.317 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YT472 UT WOS:000071607000041 PM 9450718 ER PT J AU Bahar, I Wallqvist, A Covell, DG Jernigan, RL AF Bahar, I Wallqvist, A Covell, DG Jernigan, RL TI Correlation between native-state hydrogen exchange and cooperative residue fluctuations from a simple model SO BIOCHEMISTRY LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; NUCLEAR MAGNETIC-RESONANCE; FRENCH BEAN PLASTOCYANIN; AMIDE-PROTON-EXCHANGE; COLI RIBONUCLEASE HI; CYTOCHROME-C; STAPHYLOCOCCAL NUCLEASE; CIRCULAR-DICHROISM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI AB Recently, we developed a simple analytical model based on local residue packing densities and the distribution of tertiary contacts for describing the conformational fluctuations of proteins in their folded state. This so-called Gaussian network model (GNM) is applied here to the interpretation of experimental hydrogen exchange (HX) behavior of proteins in their native state or under weakly denaturing conditions. Calculations are performed for five proteins: bovine pancreatic trypsin inhibitor, cytochrome c, plastocyanin, staphylococcal nuclease, and ribonuclease H. The results are significant in two respects, First, a good agreement is reached between calculated fluctuations and experimental measurements of HX despite the simplicity of the model and within computational times 2 or 3 orders of magnitude faster than earlier, more complex simulations. Second, the success of a theory, based on the coupled conformational fluctuations of residues near the native state, to satisfactorily describe the native-state HX behavior indicates the significant contribution of local, but cooperative, fluctuations to protein conformational dynamics. The correlation between the HX data and the unfolding kinetics of individual residues further suggests that local conformational susceptibilities as revealed by the GNM approach may have implications relevant to the global dynamics of proteins. C1 NCI, Div Basic Sci, Mol Struct Sect, Lab Expt & Computat Biol,Div Basic Sci,NIH, Bethesda, MD 20892 USA. Bogazici Univ, Polymer Res Ctr, TR-80815 Istanbul, Turkey. Bogazici Univ, Dept Chem Engn, TR-80815 Istanbul, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Istanbul, Turkey. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Jernigan, RL (reprint author), NCI, Div Basic Sci, Mol Struct Sect, Lab Expt & Computat Biol,Div Basic Sci,NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 65 TC 131 Z9 134 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 27 PY 1998 VL 37 IS 4 BP 1067 EP 1075 DI 10.1021/bi9720641 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV442 UT WOS:000071824600013 PM 9454598 ER PT J AU Hu, QH Corda, S Zweier, JL Capogrossi, MC Ziegelstein, RC AF Hu, QH Corda, S Zweier, JL Capogrossi, MC Ziegelstein, RC TI Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells SO CIRCULATION LA English DT Article DE calcium; endothelium; free radicals ID SARCOPLASMIC-RETICULUM; HYPOXIA-REOXYGENATION; LIPID-PEROXIDATION; CYTOSOLIC CALCIUM; THIOL OXIDATION; MONOLAYERS; HISTAMINE; DAMAGE; STORE; POOL AB Background-Because the vascular endothelium is exposed to oxidant stress resulting from ischemia/reperfusion and from the products of polymorphonuclear leukocytes or monocytes, studies were performed to examine the effect of hydrogen peroxide (1 mu mol/L to 10 mmol/L) on endothelial Ca2+ signaling, Methods and Results-At low concentrations (1 to 10 mu mol/L), hydrogen peroxide did not affect intracellular Ca2+ concentration in subconfluent, indo 1-loaded human aortic endothelial monolayers, At a concentration of 100 mu mol/L hydrogen peroxide, intracellular free Ca2+ gradually increased from 125.3 +/- 6.8 to 286.3 +/- 19.9 nmol/L over 4.2 +/- 0.9 minutes before repetitive Ca2+ oscillations were observed, consisting of an initial large, transient spike of approximate to 1 mu mol/L followed by several spikes of decreasing amplitudes at a frequency of 0.7 +/- 0.1 min(-1) over 12.0 +/- 1.1 minutes, After these oscillations, intracellular Ca2+ reached a plateau of 543.4 +/- 64.0 nmol/L, which was maintained above baseline levels for > 5 minutes and then partially reversible on washout of hydrogen peroxide in most monolayers, Intracellular Ca2+ oscillations were typically observed when monolayers were exposed to 100 to 500 mu mol/L hydrogen peroxide. Higher concentrations of hydrogen peroxide (1 and 10 mmol/L) increased intracellular Ca2+ but only rarely (2 of 6 monolayers at 1 mmol/L) or never (at 10 mmol/L) stimulated intracellular Ca2+ oscillations. Removal of Ca2+ from the buffer either before hydrogen peroxide stimulation or during an established response did not block intracellular Ca2+ oscillations in response to 100 mu mol/L hydrogen peroxide, but prior depletion of an intracellular Ca2+ store with either caffeine, histamine, or thapsigargin abolished Ca2+ oscillations. Conclusions-Hydrogen peroxide induces concentration-dependent intracellular Ca2+ oscillations in human endothelial cells, which results from release of an endoplasmic reticulum Ca2+ store. Because oxidant production appears to occur In the micromolar range in the postischemic/anoxic endothelium and is associated with impaired endothelium-dependent relaxation, the effects of micromolar concentrations of hydrogen peroxide on endothelial Ca2+ signaling described in the present study maybe important in the pathogenesis of postischemic endothelial dysfunction. C1 Johns Hopkins Univ, Dept Med, Div Cardiol, Johns Hopkins Bayview Med Ctr,Sch Med, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Ist Dermopat Immacolata, Lab Patol Vasc, Rome, Italy. RP Ziegelstein, RC (reprint author), Johns Hopkins Univ, Dept Med, Div Cardiol, Johns Hopkins Bayview Med Ctr,Sch Med, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM rziegels@welchlink.welch.jhu.edu FU NHLBI NIH HHS [HL-52315, HL-03102] NR 42 TC 83 Z9 85 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 1998 VL 97 IS 3 BP 268 EP 275 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YT817 UT WOS:000071648000011 PM 9462529 ER PT J AU Reinlib, L AF Reinlib, L TI Priorities in heart failure research - Response SO CIRCULATION LA English DT Letter C1 NHLBI, Div Heart & Vasc Dis, Heart Res Program, Bethesda, MD 20892 USA. RP Reinlib, L (reprint author), NHLBI, Div Heart & Vasc Dis, Heart Res Program, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 1998 VL 97 IS 3 BP 296 EP 296 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YT817 UT WOS:000071648000025 ER PT J AU Furumura, M Solano, F Matsunaga, N Sakai, C Spritz, RA Hearing, VJ AF Furumura, M Solano, F Matsunaga, N Sakai, C Spritz, RA Hearing, VJ TI Metal ligand-binding specificities of the tyrosinase-related proteins SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DOPACHROME TAUTOMERASE; BINUCLEAR COPPER; ENZYME; MELANOCYTES; ZINC; IDENTIFICATION; HYDROXYLASE; HEMOCYANIN; MELANOMA; OXIDASE AB The production of pigment in mammalian melanocytes requires the interaction of at least 3 melanogenic enzymes, which regulate the type and amount of melanins produced. All 3 known enzymes belong to the TRP gene family and share many common structural features, including two metal binding domains thought to be important to their catalytic functions. This study used radiolabeled metal ligand binding with autoradiography as well as reconstitution protocols to analyze the binding of metal cations to these enzymes. The results demonstrate that all 3 enzymes are capable of binding divalent metal cations; copper is bound to tyrosinase but not to TRP1 or TRP2, TRP2 requires zinc as its metal ligand, and small amounts of iron bound to TRP2; TRP1 did not bind copper, zinc or iron. Clearly, the specific binding of different metals by the TRPs is responsible for their distinct catalytic functions in melanogenesis. (C) 1998 Academic Press. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Murcia, Fac Med, Dept Biochem, Murcia, Spain. Univ Wisconsin, Dept Med Genet & Pediat, Genet Lab, Madison, WI 53706 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37 Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Solano, Francisco/G-5001-2013 OI Solano, Francisco/0000-0001-9612-761X NR 35 TC 39 Z9 42 U1 2 U2 6 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 JAN 26 PY 1998 VL 242 IS 3 BP 579 EP 585 DI 10.1006/bbrc.1997.8007 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YV444 UT WOS:000071824800022 PM 9464259 ER PT J AU Douglas, AJ Meeren, HKM Johnstone, LE Pfaff, DW Russell, JA Brooks, PJ AF Douglas, AJ Meeren, HKM Johnstone, LE Pfaff, DW Russell, JA Brooks, PJ TI Stimulation of expression of the oxytocin gene in rat supraoptic neurons at parturition SO BRAIN RESEARCH LA English DT Article DE oxytocin mRNA; oxytocin hnRNA; pregnancy; lactation ID MESSENGER-RIBONUCLEIC-ACID; C-FOS; VASOPRESSIN GENE; LACTATING RATS; INSITU HYBRIDIZATION; PREGNANT RATS; RNA; TRANSCRIPTION; INDUCTION; SECRETION AB We measured expression of the oxytocin gene in the supraoptic nucleus (SON) during pregnancy, parturition and lactation to examine its relationship to states of accumulation or depletion of oxytocin stores and to conditions of strong excitation of oxytocin neurons. The primary transcript (heterogeneous nuclear RNA, hnRNA) of the oxytocin gene was measured using a H-3-cDNA probe against intron 1 for in situ hybridisation. Autoradiographs of the SON showed the hnRNA as discrete clumps of silver grains within the nucleus of each neuron. The number of cells expressing oxytocin hnRNA did not change during pregnancy but increased during parturition; 10-day lactating animals showed similar increases. Oxytocin mRNA was also measured by in situ hybridisation using a H-3- or S-35-labelled oligonucleotide probe against exon C: hybridisation was seen over the cytoplasm of supraoptic neurons, but no differences were measured between virgin, mid-pregnant, preparturient, parturient or 2-day lactating rats. The data suggest that enhanced oxytocin gene transcription is not necessary to increase oxytocin stores in pregnancy. However, acute stimulation of magnocellular oxytocin neurons at parturition, which strongly increases neuron activity and secretion, results in a rapid increase in the number of cells expressing oxytocin hnRNA, and increased expression is sustained in lactation. (C) 1998 Elsevier Science B.V. C1 Univ Edinburgh, Sch Med, Dept Physiol, Edinburgh EH8 9AG, Midlothian, Scotland. Univ Nijmegen, Dept Comparat & Physiol Psychol, NL-6500 HE Nijmegen, Netherlands. Rockefeller Univ, Dept Neurobiol & Behav, New York, NY 10021 USA. NIAAA, Rockville, MD 20852 USA. RP Douglas, AJ (reprint author), Univ Edinburgh, Sch Med, Dept Physiol, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland. EM alison.j.douglas@ed.ac.uk NR 49 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 26 PY 1998 VL 782 IS 1-2 BP 167 EP 174 DI 10.1016/S0006-8993(97)01275-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZB553 UT WOS:000072484100018 PM 9519260 ER PT J AU Nowak, G Legutko, B Skolnick, P Popik, P AF Nowak, G Legutko, B Skolnick, P Popik, P TI Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE citalopram, chronic; fluoxetine, chronic; NMDA receptor; adaptation; cortex ID H-3 CGP-39653; RAT-BRAIN; ASPARTATE; DEPRESSION; IMIPRAMINE; COMPLEX AB Glycine displaces [H-3]CGP-39653 ([H-3]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) binding to the glutamate recognition site with both high and low affinity. We reported previously that chronic treatment with antidepressants reduced the proportion of high to low affinity sites, or, even eliminated the high affinity sites in case of citalopram. Here, we compared the effects of citalopram with another serotonin specific reuptake inhibitor, fluoxetine on this measure. Chronic administration of citalopram or fluoxetine eliminated high affinity glycine-displaceable [H-3]CGP-39653 binding to the mouse cortex in 78 and 56% of animals, respectively, indicating that selective serotonin reuptake inhibitors produce qualitatively similar adaptive changes at NMDA receptors, that differ from other antidepressants in this neurochemical measure. (C) 1998 Elsevier Science B.V. C1 Polish Acad Sci, Inst Pharmacol, PL-31343 Krakow, Poland. NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Nowak, G (reprint author), Polish Acad Sci, Inst Pharmacol, Smetna 12, PL-31343 Krakow, Poland. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 11 TC 57 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 26 PY 1998 VL 342 IS 2-3 BP 367 EP 370 DI 10.1016/S0014-2999(97)01589-6 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZB288 UT WOS:000072456000033 PM 9548410 ER PT J AU Munoz-Barroso, I Durell, S Sakaguchi, K Appella, E Blumenthal, R AF Munoz-Barroso, I Durell, S Sakaguchi, K Appella, E Blumenthal, R TI Dilation of the human immunodeficiency virus-1 envelope glycoprotein fusion pore revealed by the inhibitory action of a synthetic peptide from gp41 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INDUCED CELL-FUSION; INFLUENZA HEMAGGLUTININ; MEMBRANE-FUSION; VIRAL FUSION; TRANSMEMBRANE GLYCOPROTEIN; INITIAL-STAGES; TYPE-1; PROTEIN; KINETICS; RECEPTOR AB We have monitored fusion between cell pairs consisting of a single human immunodeficiency virus-1 (HIV-1) envelope glycoprotein-expressing cell and a CD4(+) target cell, which had been labeled with both a fluorescent lipid in the membrane and a fluorescent solute in the cytosol, We developed a new three-color assay to keep track of the cell into which fluorescent lipids and/or solutes are redistributed. Lipid and solute redistribution occur as a result of opening a lipid-permissive fusion pore and a solute-permissive fusion pore (FPS), respectively, A synthetic peptide (DP178) corresponding to residues 643-678 of the HIV-1(LAI) gp120-gp41 sequence (Wild, C.T., D.C. Shugars, T.K. Greenwell, C.B. McDanal, and T.J. Matthews, 1994. Proc. Natl. Acad. Sci. USA. 91:12676-12680) completely inhibited FPS at 50 ng/ml, whereas at that concentration there was 20-30% fusion activity measured by the lipid redistribution, The differences detected in lipid mixing versus contents mixing are maintained up to 6 h of coculture of gp120-41-expressing cells with target cells, indicating that DP178 can "clamp" the fusion complex in the lipid mixing intermediate for very long time periods, A peptide from the NH2-terminal of gp41, DP107, inhibited HIV-1(LAI) gp120-gp41-mediated cell fusion at higher concentrations, but with no differences between lipid and aqueous dye redistribution at the different inhibitor concentrations, The inhibition of solute redistribution by DP178 was complete when the peptide was added to the fusion reaction mixture during the first 15 min of coculture, We have analyzed the inhibition data in terms of a fusion pore dilation model that incorporates the recently determined high resolution structure of the gp41 core. C1 NIH, Lab Expt & Computat Biol, Frederick, MD USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Blumenthal, R (reprint author), Miller Dr,POB B,Bldg 469,Room 213, Frederick, MD 21702 USA. NR 48 TC 243 Z9 244 U1 2 U2 9 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 JAN 26 PY 1998 VL 140 IS 2 BP 315 EP 323 DI 10.1083/jcb.140.2.315 PG 9 WC Cell Biology SC Cell Biology GA YV186 UT WOS:000071798000007 PM 9442107 ER PT J AU Kyriakides, TR Zhu, YH Smith, LT Bain, SD Yang, ZT Lin, MT Danielson, KG Iozzo, RV LaMarca, M McKinney, CE Ginns, EI Bornstein, P AF Kyriakides, TR Zhu, YH Smith, LT Bain, SD Yang, ZT Lin, MT Danielson, KG Iozzo, RV LaMarca, M McKinney, CE Ginns, EI Bornstein, P TI Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EHLERS-DANLOS SYNDROME; V COLLAGEN; EXTRACELLULAR COMPARTMENTS; PLATELET-ADHESION; ENDOTHELIAL-CELLS; BINDING; GENE; EXPRESSION; FIBRIL; ANGIOGENESIS AB Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2-/- mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration. C1 Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Zymogenet Inc, Seattle, WA 98105 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Bornstein, P (reprint author), Univ Washington, Dept Biochem, Box 357350, Seattle, WA 98195 USA. OI Iozzo, Renato/0000-0002-5908-5112 FU NHLBI NIH HHS [P01 HL018645, P01 HL18645]; NIAMS NIH HHS [AR21557, P01 AR021557]; NIDCR NIH HHS [DE08229] NR 58 TC 310 Z9 321 U1 0 U2 3 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 JAN 26 PY 1998 VL 140 IS 2 BP 419 EP 430 DI 10.1083/jcb.140.2.419 PG 12 WC Cell Biology SC Cell Biology GA YV186 UT WOS:000071798000017 PM 9442117 ER PT J AU Miller, M Baca, M Rao, JKM Kent, SBH AF Miller, M Baca, M Rao, JKM Kent, SBH TI Probing the structural basis of the catalytic activity of HIV-1 PR through total chemical protein synthesis SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE HIV-1 proteinase; structural engineering; chemical protein synthesis; catalytic mechanism; structure-based drug design ID ASPARTIC PROTEINASES; RETROVIRAL PROTEASES; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; INHIBITOR; RESOLUTION; MECHANISM; PEPTIDES; BINDING; PENICILLOPEPSIN AB Historically, total chemical synthesis had been used to prepare native proteinase from the human immunodeficiency virus (HIV-1 PR) for structural studies by X-ray crystallography. More recently, several functionally-relevant analogues of HIV-I PR have also been obtained by total chemical synthesis. The results of structural and biochemical studies of the backbone engineered analogues put in question the established belief of the importance of an internal, tetrahedrally coordinated water molecule (water 301)in mediating catalytically important flap-substrate interaction. An enzyme analogue in which the peptide bond between residues Gly(51) and Gly(52) was replaced by a thioester moiety displayed normal enzymatic activity, while the crystal structure of its complex with the inhibitor MVT101 (solved at 2.5 Angstrom resolution as mirror image, D-enantiomer) did not show the presence of water 301. The enzyme analogue in which the ability to donate hydrogen bonds to substrate was deleted (by substitution of Ile(50)-N(H)- by a sulfur atom) in both flaps was 2500-fold less active. By contrast, the covalent dimer form of the enzyme with the Gly(49)-Ile(50) peptide bond -N(H)- atom specifically replaced by an -O- atom in one flap only retained normal enzymatic activity. The combined data from these studies strongly indicate that flap-substrate hydrogen bonds from only one flap are sufficient for full enzymatic activity of the HIV-1 PR, and raise the possibility that the retroviral enzyme may make use of only one flap in catalysis. This result may have profound implications for drug design targeted at HIV-1 PR. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res Facil & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, Frederick, MD 21702 USA. Scripps Res Inst, La Jolla, CA 92037 USA. RP Miller, M (reprint author), NCI, Frederick Canc Res Facil & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 NR 41 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 137 EP 152 DI 10.1016/S0166-1280(96)05022-1 PG 16 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800013 ER PT J AU Ma, W Zhang, L Xing, G Hu, Z Iwasa, KH Clay, JR AF Ma, W Zhang, L Xing, G Hu, Z Iwasa, KH Clay, JR TI Prenatal expression of inwardly rectifying potassium channel mRNA (Kir4.1) in rat brain SO NEUROREPORT LA English DT Article DE embryonic brain; in situ hybridization; inward rectifier; Northern blots ID K+ CHANNEL; MESSENGER-RNAS; CELLS; CLONING; FAMILY AB THE levels and cellular localization of the mRNA encoding the inwardly rectifying potassium ion channel Kir4.1 were investigated in the embryonic rat brain by Northern blots and in situ hybridization. This transcript was absent at embryonic day 13 (E13), whereas it was clearly present in E14-15 preparations, principally in the neuroepithelium of the cerebral cortex, thalamus, and hypothalamus. At later embryonic stages (E17-20), Kir4.1 mRNA levels increased and expanded to the mantle zone, such as the cortical plate, hippocampus, thalamus, and hypothalamus. The early appearance of Kir4.1 mRNA in various brain regions suggests an involvement of the channel in cell proliferation, migration and differentiation in the rat CNS. C1 Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Div Biotechnol, Rockville, MD 20850 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Communicat Disorders, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Clay, JR (reprint author), Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bldg 36,Rm 2C02, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 20 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 26 PY 1998 VL 9 IS 2 BP 223 EP 227 DI 10.1097/00001756-199801260-00009 PG 5 WC Neurosciences SC Neurosciences & Neurology GA YV807 UT WOS:000071865300009 PM 9507959 ER PT J AU Topol, IA Casas-Finet, JR Gussio, R Burt, SK Erickson, JW AF Topol, IA Casas-Finet, JR Gussio, R Burt, SK Erickson, JW TI A quantum-mechanical study of metal binding sites in zinc finger structures SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE zinc fingers; antiviral therapy; metal binding sites; density functional theory; retroviral zinc fingers ID DENSITY FUNCTIONAL CALCULATIONS; TRANSCRIPTION FACTOR-IIIA; MURINE LEUKEMIA-VIRUS; DNA-BINDING; NUCLEOCAPSID PROTEIN; CARBONIC-ANHYDRASE; GLUCOCORTICOID RECEPTOR; DOMAINS; ABINITIO; ENZYMES AB Density functional theory (DFT) methods were used to calculate geometric and electronic properties for the metal binding sites belonging to three distinct zinc finger families, as well as for that of a binuclear M(2)Cys(6) 6 sequence. DFT-derived structural parameters such as bond distances and angles for Zn-II and Cd-II binding sites were in agreement with experimental values obtained from EXAFS, X-ray crystallography, and multidimensional NMR spectroscopy for related systems. Calculations of the electronic properties of these peptides indicate that the chelating residues alone are responsible for the majority of the free energy of metal binding, with only a small contribution attributable to neighboring residues. Our calculations also predict that the binding affinity for a given metal ion increases with the number of thiolate ligands, and is consistent with experimental observations of the relative metal ion affinities for peptides from different zinc finger families. For all zinc finger families, calculated ionization potentials for Cd-II-bound peptides were larger than those for the Zn-II-bound species, leading to the prediction of faster redox reaction rates for the latter. We discuss the implications of these results for the structure and function of zinc fingers, as well as for the design of compounds affecting their chemical integrity. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, Frederick Biomed Supercomp Ctr,SAIC Frederick, Frederick, MD 21702 USA. RP Topol, IA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, Frederick Biomed Supercomp Ctr,SAIC Frederick, Frederick, MD 21702 USA. NR 62 TC 21 Z9 21 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 13 EP 28 DI 10.1016/S0166-1280(96)04874-9 PG 16 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800003 ER PT J AU Smith, RH Michejda, CJ Hughes, SH Arnold, E Janssen, PAJ Smith, MBK AF Smith, RH Michejda, CJ Hughes, SH Arnold, E Janssen, PAJ Smith, MBK TI Structure and mechanism of action of nonnucleoside inhibitors of HIV-1 reverse transcriptase: strategies to combat drug resistance SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE HIV-1 reverse transcriptase; nonnucleoside inhibitors; molecular modeling ID PI-PI-INTERACTIONS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; PROTEASE; ENERGY; DNA AB In the past few years, drug research has focused on three HIV-1 enzymes, reverse transcriptase (RT), protease, and integrase. In the case of RT, a number of potent inhibitors have been discovered. These can be classified into two distinct groups, nucleoside analogs and nonnucleoside inhibitors; however, mutations in RT have allowed the virus to develop resistance to all of the known drugs. In order to better understand the interactions between amino acid residues in the protein and nonnucleoside inhibitors, a computer model of the nonnucleoside inhibitor binding pocket of RT has been developed, using a subset of amino acid residues surrounding the pocket. The results of molecular mechanics minimizations of three RT/nonnucleoside inhibitor complexes showed that the resultant total energies of complexation (binding energies) correlated with EC50 values if and only if the calculations were carried out using coordinates from the cognate complex while allowing for adjustments of the protein relative to the inhibitor. If a model was constructed using only the crystal data of one particular RT/inhibitor complex (RT/8-Cl TIBO), the calculations did not correctly order the other inhibitors, The difficulty in devising such a "generic" model nonnucleoside binding site in HIV-1 RT is likely due to the inherent flexibility of the enzyme. A comparison of the structure(s) of HIV-1 RT in complexes with different nonnucleoside inhibitors shows that the enzyme readily adapts to the shape of each inhibitor upon complexation. In contrast to the side-chain residues of HIV protease, the amino acid residues surrounding the binding pocket in RT adopt geometries that are unique to each bound inhibitor, adopting positions that make tight van der Waals contacts. Accompanying these changes at the site where the inhibitor binds are alterations in the geometry of the nearby polymerase active site. These changes can be conveniently monitored by measuring the increase in the distance between residue G231 in the RT primer grip region and aspartyl residues (D110, D185, and D186) in the polymerase active site. The magnitude of the change in this distance correlates inversely with inhibitor EC50, suggesting a possible mechanism of action of the drugs. Calculations using a site where various amino acids residues were changed to simulate mutations in RT that induce resistance to the nonnucleoside inhibitors revealed that a combination of less favorable inhibitor-protein interactions and slight geometry changes in the polymerase active site are responsible for the decreased effectiveness of the inhibitors against mutant RTs. The modeling results are discussed with regard to both the mechanism of inhibition as well as application of these insights to strategies for the design of better nonnucleoside inhibitors. Published by Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Western Maryland Coll, Dept Chem, Westminster, MD 21157 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Janssen Res Fdn, Ctr Mol Design, B-2350 Vosselaar, Belgium. RP Smith, RH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 16 TC 10 Z9 10 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 67 EP 77 DI 10.1016/S0166-1280(97)00071-7 PG 11 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800007 ER PT J AU Chatfield, DC Eurenius, KP Brooks, BR AF Chatfield, DC Eurenius, KP Brooks, BR TI HIV-1 protease cleavage mechanism: A theoretical investigation based on classical MD simulation and reaction path calculations using a hybrid QM/MM potential SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE computer simulation; enzyme catalysis; HIV-protease; molecular dynamics; QM/MM potential ID HUMAN IMMUNODEFICIENCY VIRUS-1; MOLECULAR-DYNAMICS SIMULATION; STATE-ANALOG INHIBITOR; BINDING FREE-ENERGIES; ASPARTIC PROTEINASES; ACTIVE-SITE; COMBINED QUANTUM; ENZYME PHOSPHOLIPASE-A2; AQUEOUS-SOLUTION; CHEMICAL MECHANISM AB The cleavage mechanism of HIV-1 protease (HIV-PR) is investigated with classical molecular dynamics (MD) simulation and with methods incorporating a hybrid quantum mechanical and molecular mechanical (QM/MM) potential function. An Xray structure of an HIV-PR/inhibitor complex was used to generate model HIV-PR/substrate and HIV-PR/intermediate complexes. Analysis of the feasibility of reaction is based on three hypothetical reaction mechanisms and a variety of possible starting conditions. The classical MD simulations were analyzed for conformations consistent with reaction initiation, as reported previously. It was concluded that Asp125 is the general acid in the first reaction step and transfers a proton to the carbonyl oxygen. Simulations suggest that water 301 stabilizes productive reactant and intermediate conformations but does not participate directly in the reaction. A lytic water, when present, is held very tightly in a position propitious for nucleophilic attack at the scissile carbon. For mechanisms consistent with the classical simulations, reaction barriers were calculated using a QM/MM potential. The QM/MM potential and a restrained energy minimization method for calculating reaction paths and barriers are described. Preliminary results identify reasonable barrier heights and transition state conformations and predict that the first reaction step follows a predominantly stepwise rather than concerted pathway. (C) 1998 Elsevier Science B.V. C1 Florida Int Univ, Dept Chem, Miami, FL 33199 USA. NIH, Div Comp Res & Technol, Struct Biol Lab, Bethesda, MD 20892 USA. RP Chatfield, DC (reprint author), Florida Int Univ, Dept Chem, Univ Pk, Miami, FL 33199 USA. NR 81 TC 38 Z9 38 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 79 EP 92 DI 10.1016/S0166-1280(96)04875-0 PG 14 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800008 ER PT J AU Covell, DG Jernigan, RL Wallqvist, A AF Covell, DG Jernigan, RL Wallqvist, A TI Structural analysis of inhibitor binding to HIV-1 protease: identification of a common binding motif SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE HIV-1 protease; inhibitor binding; mutations; cross-resistance ID HUMAN IMMUNODEFICIENCY VIRUS-1; CRYSTAL-STRUCTURES; TYPE-1 VARIANTS; ACTIVE-SITE; ENERGY; PROTEINS; COMPLEX; DESIGN; RECOGNITION; RESISTANCE AB Analysis of coordinates from ten crystal structures of HIV-I protease-inhibitor complexes (HIV-I-Pr) reveals that the energetically important contacts formed in these complexes involve a rather limited number of atoms from only a few highly mutable residues. This common binding motif relies primarily on hydrogen bonds to position each inhibitor between the catalytic and the flap residues of HIV-1 protease, together with a set of hydrophobic interactions that flank the lengthwise edges of these inhibitors. Nine of thirteen known drug resistant HIV-1 protease mutations are located directly within this motif. These striking similarities in the details of inhibitor binding suggest that escape mutants arising from treatment with any one of these HIV-1 protease inhibitors will likely confer cross-resistance to other inhibitors utilizing the same binding pattern. It is suggested that the stability of the natural substrate, in contrast to the more rigid synthetic inhibitors, facilitates its adaptation to bind, for catalysis. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Math Biol Lab, Bethesda, MD 20892 USA. RP Covell, DG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RI Jernigan, Robert/A-5421-2012; OI wallqvist, anders/0000-0002-9775-7469 NR 42 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 93 EP 100 DI 10.1016/S0166-1280(97)00122-X PG 8 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800009 ER PT J AU Pramodh, V Pattabiraman, N Le, SY Maizel, JV AF Pramodh, V Pattabiraman, N Le, SY Maizel, JV TI A molecular modeling study of antibiotics-RNA interactions: application to HIV-1 Rev response element SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE molecular modeling; antibiotics-RNA interaction; HIV-1 Rev response element ID VIRUS TYPE-III; BINDING-ELEMENT; MESSENGER-RNA; FORCE-FIELD; BASE-PAIRS; RECOGNITION; PEPTIDE; PROTEIN; SITE AB HIV-1 Rev protein interaction with the Response Element (RRE) RNA is important for the regulation and gene expression in HIV-1. Molecules that inhibit this interaction are potential anti-HIV drugs, Some aminoglycoside antibiotics, such as neomycin B and tobramycin, have been found to inhibit the binding of Rev to RRE by specifically binding to the high-affinity binding site of RRE. In this paper, we present a three-dimensional model for these antibiotics-RRE complexes, From our modeling studies, we found these antibiotics to have restricted conformations both in the bound and unbound state, In the restricted conformations four of the amino groups point to one side of the antibiotic molecule such that they can form salt bridges with the phosphate groups of U45, G47 and G48 in the case of tobramycin and with the phosphate groups of A44, G47 and G48 in the case of neomycin B, In addition, some of the amino and hydroxyl groups in the antibiotics interact favorably with N7 and/or O6 atoms of GGG (nt 46-48). In the antibiotics-RNA complexes, the two non-Watson-Crick base pairs are formed as observed in the case of Rev and the 17mer peptide from Rev when bound to RRE, These models are consistent with the known footprinting data and also the inhibitory data for these antibiotics against the binding of Rev to RRE, These models could be used to develop a pharmacophore to search for compounds in the chemical databases that can inhibit the binding of Rev to RRE. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Indian Inst Technol, Dept Chem, Bombay 400076, Maharashtra, India. NCI, Div Basic Sci, Math Biol Lab, Frederick, MD 21702 USA. RP Pattabiraman, N (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, Sci Applicat Int Corp, POB B, Frederick, MD 21702 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 125 EP 136 DI 10.1016/S0166-1280(96)05021-X PG 12 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800012 ER PT J AU Sze'kely, Z Fabian, P Torday, LL Michejda, CJ Aszalos, A AF Sze'kely, Z Fabian, P Torday, LL Michejda, CJ Aszalos, A TI Binding between the CD4 receptor and polysulfonated azo-dyes. An exploratory theoretical study on action-mechanism SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE HIV entry; CD4; gp120; antiviral drug; docking ID IMMUNODEFICIENCY-VIRUS; SURAMIN; CELLS AB The antiviral mechanism of action of the polysulfonated ate-dyes is discussed in this paper. Crucial to the antiviral activity of these dyes is the inhibition of the HIV entry into the host cell, This is a result of the covering strategic areas of the CD4 viral receptor surface. A consistent, mainly electrostatic, interaction model has been established to explain the mode of inhibition activity of Direct Red 79 and Direct Yellow 50, The basis of the model is a dynamic distance matrix of the most important positively charged amino acid side chains within the CD4, which might serve as an electrostatic docking site for the negatively charged sulfonate groups of the ate-dyes. Beside the intrinsic value of interpreting the biological effect, this model might serve as a useful tool for a rational drug design. Published by Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Albert Szent Gyorgyi Med Univ, Dept Med Chem, H-6701 Szeged, Hungary. Agr Biotechnol Ctr, Inst Biochem, H-2101 Godollo, Hungary. Albert Szent Gyorgyi Med Univ, Dept Pharmacol, H-6701 Szeged, Hungary. US FDA, Ctr Drug Evaluat & Res, Div Res & Testing, Washington, DC 20204 USA. RP Sze'kely, Z (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Torday, Laszlo/J-7899-2012 OI Torday, Laszlo/0000-0002-2911-5499 NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 153 EP 159 DI 10.1016/S0166-1280(97)00363-1 PG 7 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800014 ER PT J AU Grether, J Hirtz, D McNellis, D Nelson, K Rouse, DJ AF Grether, J Hirtz, D McNellis, D Nelson, K Rouse, DJ TI Tocolytic magnesium sulphate and paediatric mortality SO LANCET LA English DT Letter ID CEREBRAL-PALSY; RISK C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NICHHD, Bethesda, MD 20892 USA. CA State Dept Hlth, Calif Birth Defects Monitoring Program, Emeryville, CA USA. RP Nelson, K (reprint author), NINDS, Neuroepidemiol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 5 TC 13 Z9 13 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 24 PY 1998 VL 351 IS 9098 BP 292 EP 292 DI 10.1016/S0140-6736(05)78239-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YU294 UT WOS:000071702200055 PM 9457123 ER PT J AU Gutkind, JS AF Gutkind, JS TI The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID BETA-GAMMA-SUBUNITS; MAP KINASE; TYROSINE-KINASE; GROWTH-FACTOR; SIGNALING PATHWAY; LYSOPHOSPHATIDIC ACID; DEPENDENT ACTIVATION; ALPHA-SUBUNIT; CELL-GROWTH; PHOSPHORYLATION C1 NIDR, Oral & Pharyngeal Canc Branch, Cell Growth Control Sect, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, Cell Growth Control Sect, NIH, Bldg 30,Rm 212,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 73 TC 624 Z9 635 U1 2 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 JAN 23 PY 1998 VL 273 IS 4 BP 1839 EP 1842 DI 10.1074/jbc.273.4.1839 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200001 PM 9442012 ER PT J AU Demaurex, N Furuya, W D'Souza, S Bonifacino, JS Grinstein, S AF Demaurex, N Furuya, W D'Souza, S Bonifacino, JS Grinstein, S TI Mechanism of acidification of the trans-Golgi network (TGN) - In situ measurements of pH using retrieval of TGN38 and furin from the cell surface SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VACUOLAR H+-ATPASE; CYTOPLASMIC DOMAIN; INTRACELLULAR PH; CA2+/H+ EXCHANGE; CYSTIC-FIBROSIS; LIVING CELLS; BREFELDIN-A; LOCALIZATION; MEMBRANE; SEQUENCE AB Sorting of secretory cargo and retrieval of components of the biosynthetic pathway occur at the trans-Golgi network (TGN), The pH within the TGN is thought to be an important determinant of these functions, However, studies of the magnitude and regulation of the pH of the TGN have been hampered by the lack of appropriate detection methods, This report describes a noninvasive strategy to measure the luminal pH of the TGN in intact cells, We took advantage of endogenous cellular mechanisms for the specific retrieval of TGN resident proteins, such as TGN38 and furin, that transit briefly to the plasma membrane, Cells were transfected with chimeric constructs that contained the internalization and retrieval signals of TGN resident proteins, and a luminal (extracellular) epitope (CD25), Like TGN38 and furin, the chimeras were shown by fluorescence microscopy to accumulate within the TGN, During their transient exposure at the cell surface, the chimeras were labeled with extracellular anti-CD25 antibodies conjugated with a pH-sensitive fluorophore. Subsequent endocytosis and retrograde transport resulted in preferential labeling of the TGN with the pH-sensitive probe, Continuous, quantitative measurements of the pH of the TGN were obtained by ratio fluorescence imaging, The resting pH, calibrated using either ionophores or the "null point" technique, averaged 5.95 in Chinese hamster ovary cells and 5.91 in HeLa cells, The acidification was dissipated upon addition of concanamycin, a selective blocker of vacuolar-type ATPases, The counterion conductance was found to be much greater than the rate of H+ pumping at the steady state, suggesting that the acidification is not limited by an electrogenic potential, Both Cl- and K+ were found to contribute to the overall counterion permeability of the TGN, No evidence was found for the presence of active Na+/H+ or Ca2+/H+ exchangers on the TGN membrane, In conclusion, selective retrieval of recombinant proteins can be exploited to target ion-sensitive fluorescent probes to specific organelles, The technique provides real-time, noninvasive, and quantitative determinations of the pH, allowing the study of pH regulation within the TGN in intact cells, The acidic pH of the TGN reflects active H+ pumping into an organelle with a low intrinsic H+ permeability and a high conductance to monovalent ions. C1 Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. Univ Geneva, Med Ctr, Dept Physiol, CH-1211 Geneva, Switzerland. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. RP Grinstein, S (reprint author), Hosp Sick Children, Div Cell Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM sga@sickkids.on.ca OI Bonifacino, Juan S./0000-0002-5673-6370 NR 37 TC 138 Z9 143 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 JAN 23 PY 1998 VL 273 IS 4 BP 2044 EP 2051 DI 10.1074/jbc.273.4.2044 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200031 PM 9442042 ER PT J AU Bayewitch, ML Avidor-Reiss, T Levy, R Pfeuffer, T Nevo, I Simonds, WF Vogel, Z AF Bayewitch, ML Avidor-Reiss, T Levy, R Pfeuffer, T Nevo, I Simonds, WF Vogel, Z TI Differential modulation of adenylyl cyclases I and II by various G(beta) subunits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; G-PROTEINS; CELLS; EXPRESSION; BRAIN; RESPONSIVENESS; PURIFICATION; ACTIVATION; DIVERSITY; CLONING AB The accepted dogma concerning the regulation of adenylyl cyclase (AC) activity by G(beta gamma) dimers states that the various isoforms of AC respond differently to the presence of free G(beta gamma) It has been demonstrated that AC I activity is inhibited and AC II activity is stimulated by G(beta gamma) subunits, This result does not address the possible G differences in modulation that may exist among the different G(beta gamma) heterodimers, Six isoforms of G(beta) and 12 isoforms of G(gamma) have been cloned to date, We have established a cell transfection system in which G(beta) and G(gamma) cDNAs were cotransfected with either AC isoform I or II and the activity of these isoforms was determined, We found that while AC I activity was inhibited by both G(beta 1/gamma 2) and G(beta 5/gamma 2) combinations, AC II responded differentially and was stimulated by G(beta 1/gamma 2). This finding demonstrates differential modulatory activity by different combinations of G(beta gamma) on the same AC isoform and demonstrates another level of complexity within the AC signaling system. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. Univ Dusseldorf, Dept Physiol Chem 2, D-40225 Dusseldorf, Germany. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM bnvogel@weizmann.weizmann.ac.il FU NIDA NIH HHS [DA-06265] NR 33 TC 70 Z9 70 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 1998 VL 273 IS 4 BP 2273 EP 2276 DI 10.1074/jbc.273.4.2273 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200060 PM 9442071 ER PT J AU Leong, GM Wang, KS Marton, MJ Blanco, JCG Wang, IM Rolfes, RJ Ozato, K Segars, JH AF Leong, GM Wang, KS Marton, MJ Blanco, JCG Wang, IM Rolfes, RJ Ozato, K Segars, JH TI Interaction between the retinoid X receptor and transcription factor IIB is ligand-dependent in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-HORMONE RECEPTOR; PROLIFERATOR-ACTIVATED RECEPTOR; TATA-BINDING PROTEIN; RNA-POLYMERASE-II; FACTOR-TFIIB; NUCLEAR RECEPTOR; BASAL TRANSCRIPTION; ACID RECEPTORS; RXR-ALPHA; PREINITIATION COMPLEX AB The retinoid X receptor (RXR) influences gene activation through heterodimeric and homodimeric association with DNA and associates with TATA binding protein, TAF110, and cAMP response element-binding protein-binding protein; yet the molecular mechanisms responsible for gene activation by RXRs remain incompletely defined. Since the general transcription factor IIB (TFIIB) is a common target of sequence-specific transcriptional activators, we suspected that RXR might regulate target genes via an interaction with TFIIB. Coimmunoprecipitation, far Western analysis, and glutathione S-transferase binding studies indicated that murine RXR beta (mRXR beta) was capable of binding to human TFIIB in vitro. Functional analysis with a dual-hybrid yeast system and cotransfection assays revealed the interaction of mRXR beta with TFIIB to be ligand-dependent in vivo. Truncation experiments mapped the essential binding regions to the carboxyl region of mRXR beta (amino acids (aa) 254-389) and two regions in the carboxyl region of TFIIB (aa 178-201 and aa 238-271). Furthermore, the Delta 390-410 mRXR beta mutant bound to TFIIB in vitro but was not active in the dual-hybrid yeast system, suggesting that the extreme carboxyl region of RXR was required for in vivo interaction with TFIIB. These data indicate that interaction of mRXR beta with TFIIB is specific, direct, and ligand-dependent in vivo and suggest that gene activation by RXR involves TFIIB. C1 NICHHD, Unit Mol Mechanisms Reprod, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Segars, JH (reprint author), Uniformed Serv Univ Hlth Sci, OSD, Bldg A,Rm 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NICHD NIH HHS [Z01-HD00636] NR 89 TC 13 Z9 13 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 JAN 23 PY 1998 VL 273 IS 4 BP 2296 EP 2305 DI 10.1074/jbc.273.4.2296 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200063 PM 9442074 ER PT J AU Louis, JM Martin, RG Clore, GM Gronenborn, AM AF Louis, JM Martin, RG Clore, GM Gronenborn, AM TI Preparation of uniformly isotope-labeled DNA oligonucleotides for NMR spectroscopy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 4-DIMENSIONAL HETERONUCLEAR NMR; PROTEIN NMR; RNA; C-13; ENHANCEMENT; OLIGOMERS; DODECAMER; LARGER AB Two methods for the large scale preparation of uniformly isotope-labeled DNA for NMR studies have been developed, The first method comprises the growth of a suitable plasmid harboring multiple copies of the desired oligonucleotide in a medium based on N-15 and C-13 nutrients. The second method uses a polymerase chain reaction (PCR)-based approach with N-15-and/or C-13-labeled deoxynucleoside triphosphates. The novelty of our PCR strategy over existing ones is that the primer and template are the identical molecule, resulting in an exponential growth in the length of the double strand that contains tandem repeats of the target DNA sequence. This novel PCR approach, which we have termed ESRA for endonuclease-sensitive repeat amplification, is easy to use, results in high fields, and can be accomplished at low costs, The utility of both methods is demonstrated for the preparation of a double-stranded 21-mer uniformly labeled with N-15 and a double-stranded 17-mer DNA uniformly labeled with N-15 and C-13. 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, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 32 TC 50 Z9 50 U1 0 U2 5 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 JAN 23 PY 1998 VL 273 IS 4 BP 2374 EP 2378 DI 10.1074/jbc.273.4.2374 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200073 PM 9442084 ER PT J AU Chestkov, VV Radko, SP Cho, MS Chrambach, A Vogel, SS AF Chestkov, VV Radko, SP Cho, MS Chrambach, A Vogel, SS TI Reconstitution of calcium-triggered membrane fusion using "reserve" granules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEA-URCHIN EGGS; MEDIATING CELL-ADHESION; EXTRACELLULAR-MATRIX; PLASMA-MEMBRANE; BIOLOGICAL-MEMBRANES; REGULATED SECRETION; VESICLE EXOCYTOSIS; YOLK PLATELETS; PROTEINS; ATP AB Calcium-gated secretion of proteins involves the transfer of "reserve" granules, exocytotic vesicles that are cytoplasmic and, hence, plasma membrane-naive, from the cell interior to the surface membrane where they dock prior to fusion. Docking and subsequent priming steps are thought to require cytoplasmic factors. These steps are believed to induce fusion competence. We have tested this hypothesis by isolating reserve granules from sea urchin eggs and determining under which conditions these granules will fuse, We find that isolated reserve granules, lacking soluble cofactors, support calcium-dependent membrane fusion in vitro, Preincubation with adenosine 5'-3-O-(thio)triphosphate and guanosine 5'-3-O-(thio)triphosphate did not prevent fusion, Thus, isolated reserve granules have all the necessary components required for calcium-gated fusion prior to docking. C1 Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. NINDS, Synapt Mechanisms Sect, NIH, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Russian Acad Med Sci, Ctr Genet Med, Moscow, Russia. RP Vogel, SS (reprint author), Med Coll Georgia, Inst Mol Med & Genet, 1120 15th St CB 2803, Augusta, GA 30912 USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 60 TC 20 Z9 20 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 JAN 23 PY 1998 VL 273 IS 4 BP 2445 EP 2451 DI 10.1074/jbc.273.4.2445 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200084 PM 9442095 ER PT J AU Argade, AB Haugwitz, RD Devraj, R Kozlowski, J Fanwick, PE Cushman, M AF Argade, AB Haugwitz, RD Devraj, R Kozlowski, J Fanwick, PE Cushman, M TI Highly efficient diastereoselective Michael addition of various thiols to (+)-brefeldin A SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BREFELDIN-A; CELLS AB The Michael addition of thiols to brefeldin A occurs with high diastereoselectivity, affording ratios of major to minor diastereomers of at least 30:1. On the basis of the X-ray structure of a crystalline dibenzoyl derivative, the major diastereomers are assigned the 3R configuration, while the minor diastereomers have the 3S configuration. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NCI, Dev Therapeut Program, Div Canc Biol Diag & Ctr, NIH, Rockville, MD 20852 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NR 13 TC 17 Z9 17 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 23 PY 1998 VL 63 IS 2 BP 273 EP 278 DI 10.1021/jo971292y PG 6 WC Chemistry, Organic SC Chemistry GA YV188 UT WOS:000071798200013 ER PT J AU Zhang, RX Ruda, MA Qiao, JT AF Zhang, RX Ruda, MA Qiao, JT TI Pre-emptive intrathecal Mk-801, a non-competitive N-methyl-D-aspartate receptor antagonist, inhibits the up-regulation of spinal dynorphin mRNA and hyperalgesia in a rat model of chronic inflammation SO NEUROSCIENCE LETTERS LA English DT Article DE Mk-801; N-methyl-D-aspartate receptor; hyperalgesia; dynorphin mRNA; complete Freund's adjuvant; spinal cord; rats ID UNILATERAL INFLAMMATION; THERMAL NOCICEPTION; EXPRESSION; NEURONS; HYBRIDIZATION; GLUTAMATE; GENE; ACID AB The effects of N-methyl-D-aspartate(NMDA) receptor antagonist, Mk-801, on the expression of spinal dynorphin (DYN) mRNA and the hyperalgesia induced by peripheral inflammation were studied by Northern analysis and behavioral test. Following an unilateral injection of complete Freund's adjuvant (CFA) into the rat hindpaw, there appeared a significant hyperalgesia of inflamed hindpaw and up-regulation of ipsilateral spinal DYN mRNA; while the pre-emptive and continuous intrathecal administration of Mk-801 (10 mu g/mu l per h) could significantly suppress both the hyperalgesia and the up-regulation of spinal DYN mRNA induced by peripheral inflammation. The results suggest that NMDA receptor activation may contribute to the development and maintenance of the thermal hyperalgesia that is associated with the up-regulation of DYN expression in spinal dorsal horn. (C) 1998 Elsevier Science Ireland Ltd. C1 Shanxi Med Univ, Dept Neurobiol, Taiyuan 030001, Shanxi, Peoples R China. NIDR, Neurobiol & Anesthesiol Branch, NIH, Bethesda, MD 20892 USA. RP Qiao, JT (reprint author), Shanxi Med Univ, Dept Neurobiol, Taiyuan 030001, Shanxi, Peoples R China. NR 21 TC 19 Z9 21 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 23 PY 1998 VL 241 IS 1 BP 57 EP 60 DI 10.1016/S0304-3940(97)00969-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YV379 UT WOS:000071816900015 PM 9502215 ER PT J AU Schmidt, PJ Nieman, LK Danaceau, MA Adams, LF Rubinow, DR AF Schmidt, PJ Nieman, LK Danaceau, MA Adams, LF Rubinow, DR TI Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TENSION SYNDROME; DIAGNOSTIC-CRITERIA; DEPOT LEUPROLIDE; HORMONE AGONIST; PROGESTERONE; MANAGEMENT; BUSERELIN; SYMPTOMS; ESTROGEN; SCALES AB Background The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. Methods We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. Results The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. Conclusions In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes. (C) 1998, Massachusetts Medical Society. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bldg 10,Rm 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 29 TC 349 Z9 358 U1 3 U2 15 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 1998 VL 338 IS 4 BP 209 EP 216 DI 10.1056/NEJM199801223380401 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YT358 UT WOS:000071594100001 PM 9435325 ER PT J AU Rampalli, AM Gao, CY Chauthaiwale, VM Zelenka, PS AF Rampalli, AM Gao, CY Chauthaiwale, VM Zelenka, PS TI pRb and p107 regulate E2F activity during lens fiber cell differentiation SO ONCOGENE LA English DT Article DE differentiation; cell cycle; tumor suppressors; lens; E2F; transcription factors ID TRANSCRIPTION FACTOR E2F; B-MYB TRANSCRIPTION; RETINOBLASTOMA PROTEIN; CYCLE REGULATION; IN-VIVO; TRANSGENIC MICE; FACTOR DRTF1/E2F; GENE FAMILY; MOUSE LENS; EXPRESSION AB During growth arrest and differentiation, activity of the E2F family of transcription factors is inhibited by interactions with pRb and the related proteins, p107 and p130. To determine which members of the E2F and pRb families may contribute to growth arrest as lens epithelial cells differentiate into fiber cells, we examined the expression of individual E2F species and characterized the E2F protein complexes formed in rat lens epithelia and fibers. RT/PCR detected all five known members of the E2F family in lens epithelial cells, but only E2F-1, E2F-3, and E2F-5 in fiber cells. Proteins extracted from lens epithelia of newborn rats formed at least two specific complexes with an E2F consensus oligonucleotide. Proteins from lens fiber cells formed three specific complexes, one of which comigrated with an epithelial cell complex. Incubation of epithelial and fiber cell extracts with an antibody specific for p107 demonstrated that two fiber cell complexes and one epithelial cell complex contained p107. Although the remaining fiber cell complex did not react with antibodies to pRb or p130 in this assay, a strong reaction with pRb antibody was observed when the electromobility shifted complexes were subsequently immunoblotted (shift/Western assay). Immunocytochemistry confirmed that pRb protein is present in the nuclei of both epithelial cells and fiber cells. Immunoblotting of whole cell extracts with pRb antibody showed multiple, phosphorylated forms of pRb in the epithelial cells, but predominantly hypophosphorylated pRb in the fiber cells. None of the complexes formed with E2F were recognized exclusively by the p130 antibody, although the previously identified p107 complexes reacted weakly. The absence of p130/E2F complexes was correlated with the presence of multiple ubiquitinated forms of p130, especially in the fiber cells. Thus, although p130/E2F complexes are implicated in the terminal differentiation of many cell types, in differentiating lens fiber cells pRb and p107 seem to be the primary regulators of E2F activity. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 73 TC 31 Z9 31 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 22 PY 1998 VL 16 IS 3 BP 399 EP 408 DI 10.1038/sj.onc.1201546 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YT262 UT WOS:000071582100012 PM 9467965 ER PT J AU Wallqvist, A Covell, DG Thirumalai, D AF Wallqvist, A Covell, DG Thirumalai, D TI Hydrophobic interactions in aqueous urea solutions with implications for the mechanism of protein denaturation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS; WATER; SOLVATION; SIMULATIONS C1 Univ Maryland, Inst Phys Sci & Technol, Dept Chem & Biochem, College Pk, MD 20742 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Dept Chem & Biochem, College Pk, MD 20742 USA. OI wallqvist, anders/0000-0002-9775-7469 NR 20 TC 212 Z9 217 U1 2 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 21 PY 1998 VL 120 IS 2 BP 427 EP 428 DI 10.1021/ja972053v PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA YT612 UT WOS:000071624500026 ER PT J AU Chow, WH Blot, WJ Vaughn, TL Risch, HA Gammon, MD Stanford, JL Dubrow, R Schoenberg, JB Mayne, ST Farrow, DC Ahsan, H West, AB Rotterdam, H Niwa, S Fraumeni, JF AF Chow, WH Blot, WJ Vaughn, TL Risch, HA Gammon, MD Stanford, JL Dubrow, R Schoenberg, JB Mayne, ST Farrow, DC Ahsan, H West, AB Rotterdam, H Niwa, S Fraumeni, JF TI Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article AB Background: Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma, We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington, Methods: Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, ses, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index: (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. Results: The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. Conclusions: Increasing prevalence of obesity in the United States population have contributed to the upward may trends in esophageal and gastric cardia adenocarcinomas. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Int Epidemiol Inst, Rockville, MD USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA. New Jersey Dept Hlth & Senior Serv, Appl Canc Epidemiol Program, Trenton, NJ USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Westat Inc, Rockville, MD USA. RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA57923, CA57949, CA57983] NR 27 TC 399 Z9 411 U1 1 U2 3 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 JAN 21 PY 1998 VL 90 IS 2 BP 150 EP 155 DI 10.1093/jnci/90.2.150 PG 6 WC Oncology SC Oncology GA V2653 UT WOS:000165537400015 PM 9450576 ER PT J AU McLaughlin, JK Nyren, O Blot, WJ Yin, L Josefsson, S Fraumeni, JF Adami, HO AF McLaughlin, JK Nyren, O Blot, WJ Yin, L Josefsson, S Fraumeni, JF Adami, HO TI Cancer risk among women with cosmetic breast implants: a population-based cohort study in Sweden SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article C1 Int Epidemiol Inst, Rockville, MD 20850 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP McLaughlin, JK (reprint author), Int Epidemiol Inst, 1550 Res Blvd, Rockville, MD 20850 USA. NR 21 TC 41 Z9 41 U1 0 U2 2 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 JAN 21 PY 1998 VL 90 IS 2 BP 156 EP 158 DI 10.1093/jnci/90.2.156 PG 3 WC Oncology SC Oncology GA V2653 UT WOS:000165537400016 PM 9450577 ER PT J AU Suryanarayana, K Wiltrout, TA Vasquez, GM Hirsch, VM Lifson, JD AF Suryanarayana, K Wiltrout, TA Vasquez, GM Hirsch, VM Lifson, JD TI Plasma SIV RNA viral load determination by real-time quantification of product generation in reverse transcriptase-polymerase chain reaction SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-1 INFECTION; RHESUS-MONKEYS; PCR; MACAQUES; QUANTITATION; IMMUNIZATION; VACCINE; DNA AB Internally controlled RT-PCR methods (QC-RT-PCR) for quantification of SIV RNA are effective, but are relatively cumbersome, expensive, and time and labor intensive, For greater throughput and efficiency, we have developed a method for quantification of plasma SIV RNA levels by real-time RT-PCR using the Applied Biosystems Prism 7700 sequence detection system, This assay format allows real-time kinetic analysis of PCR product generation, providing a broad linear dynamic range and ensuring that quantification is based on analysis during the exponential phase of amplification, regardless of the input template copy number, Simultaneous amplification and analysis eliminates any requirement for handling amplified products, increasing throughput and eliminating a potential source of assay contamination, The assay we have developed for quantification of SIV RNA has a nominal threshold sensitivity of 300 copy Eq/ml of plasma, although as little as 10 copy Eq/reaction of SIV RNA template can be detected, The linear dynamic range is in excess of 5 logs, Interassay reproducibility averages 25% (coefficient of variation), based on studies of extraction and analysis of replicate aliquots of the same plasma specimens, The combination of sensitivity, precision, and broad dynamic range allows reliable quantification of viral load even during dynamic phases of SIV infection, such as through the onset and resolution of primary infection, or during treatment with antiretroviral agents, The primer-probe combinations we have developed allow quantification of SIV isolates most commonly used for experimental studies, Availability of this assay should greatly facilitate studies of basic pathogenesis and evaluation of therapeutic and prophylactic approaches in the SIV-infected macaque. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Retroviral Pathogenesis, AIDS Vaccine Program,SAIC Frederick, Frederick, MD 21702 USA. NIAID, Infect Dis Lab, Twinbrook Facil 2, Rockville, MD 20852 USA. RP Lifson, JD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Retroviral Pathogenesis, AIDS Vaccine Program,SAIC Frederick, Bldg 535,Room 509, Frederick, MD 21702 USA. NR 27 TC 188 Z9 189 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1998 VL 14 IS 2 BP 183 EP 189 DI 10.1089/aid.1998.14.183 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YT559 UT WOS:000071619200011 PM 9462929 ER PT J AU Singh, SB Beard, WA Hingerty, BE Wilson, SH Broyde, S AF Singh, SB Beard, WA Hingerty, BE Wilson, SH Broyde, S TI Interactions between DNA polymerase beta and the major covalent adduct of the carcinogen (+)-anti-benzo[a]pyrene diol epoxide with DNA at a primer-template junction SO BIOCHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; ESCHERICHIA-COLI PLASMID; SOLUTION CONFORMATION; OPTICAL ENANTIOMERS; NUCLEAR EXTRACT; BENZOPYRENE; PROTEINS; SITE; 7,8-DIOL-9,10-EPOXIDES; MUTAGENESIS AB A molecular dynamics simulation has been carried out with DNA polymerase beta (beta pol) complexed with a DNA primer-template. The templating guanine at the polymerase active site was covalently modified by the carcinogenic metabolite of benzo[a]pyrene, (+)-anti-benzo[a]pyrene diol epoxide, to form the major (+)-trans-anti-benzo[a]pyrene diol epoxide covalent adduct. Thus, the benzo[a]pyrenyl moiety (BP) is situated in the single-stranded template at the junction between double-and single-stranded DNA. The starting structure was based on the X-ray crystal structure of the rat beta pol primer-template and ddCTP complex [Pelletier, H., Sawaya, M. R., Kumar, A., Wilson, S. H., and Kraut, J. (1994) Science 264, 1891-1903]. During the simulation, the BP and its attached templating guanine rearrange to form a structure in which the BP is closer to parallel with the adjacent base pair. In addition, the templating attached Led guanine is displaced toward the major groove side and access to its Watson-Crick edge is partly obstructed. This structure is stabilized, in part, by new hydrogen bonds between the BP and beta pol Asn(279) and Arg(283). These residues are within hydrogen bonding distance to the incoming ddCTP and templating guanine, respectively, in the crystal structure of the beta pol ternary complex. Site-directed mutagenesis has confirmed their role in dNTP binding, discrimination, and catalytic efficiency [Beard, W. A., Osheroff, W. P., Prasad, ii., Sawaya, M. R., Jaju, M., Wood, T. G., Kraut, J., Kunkel, T. A., and Wilson, S. H. (1996) J. Biol. Chem. 271, 12141-12144]. The predominant biological effect of the BP is DNA polymerase blockage. Consistent with this biological effect, the computed structure suggests the possibility that the BP's main deleterious impact on DNA synthesis might result at least in part from its specific interactions with key polymerase side chains. Moreover, relatively modest movement of BP and its attached guanine, with some concomitant enzyme motion, is necessary to relieve the obstruction and permit the observed rare incorporation of a dATP opposite the guanine lesion. C1 NYU, Dept Biol, New York, NY 10003 USA. Merck & Co Inc, Merck Sharp & Dohme Res Labs, Rahway, NJ 07065 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. RP Broyde, S (reprint author), NYU, Dept Biol, New York, NY 10003 USA. FU NCI NIH HHS [CA-28038]; NCRR NIH HHS [RR-06458] NR 49 TC 15 Z9 15 U1 0 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 JAN 20 PY 1998 VL 37 IS 3 BP 878 EP 884 DI 10.1021/bi9720639 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU546 UT WOS:000071728700012 PM 9454577 ER PT J AU Cushman, M Casimiro-Garcia, A Williamson, K Rice, WG AF Cushman, M Casimiro-Garcia, A Williamson, K Rice, WG TI Synthesis of a non-nucleoside reverse transcriptase inhibitor in the alkenyldiarylmethane (ADAM) series with optimized potency and therapeutic index SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID VIRUS TYPE-1 HIV-1; BIOLOGICAL EVALUATION; SELECTIVE-INHIBITION; DERIVATIVES; NNRTIS; INFECTIONS; RESISTANCE AB A novel alkenyldiarylmethane (ADAM) analog has been synthesized with enhanced potency as an anti-HIV agent. The new compound (ADAM II) inhibits the cytopathic effect of HIV-1(RF) in CEM-SS cells with an EC50 of 13 nM, while it shows cytotoxicity with a CC50 of 31.6 mu M, providing a therapeutic index of 2430. ADAM II is a non-nucleoside reverse transcriptase inhibitor, displaying an IC50 of 0.3 mu M with poly(rC) oligo(dG) as the template/primer. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Lab Antiviral Drug Mechanisms, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. FU NIAID NIH HHS [N01-AI-36624] NR 17 TC 22 Z9 22 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 JAN 20 PY 1998 VL 8 IS 2 BP 195 EP 198 DI 10.1016/S0960-894X(97)10214-1 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA YU146 UT WOS:000071686900016 PM 9871653 ER PT J AU Jones, TL Chong, LD Kim, J Xu, RH Kung, HF Daar, IO AF Jones, TL Chong, LD Kim, J Xu, RH Kung, HF Daar, IO TI Loss of cell adhesion in Xenopus laevis embryos mediated by the cytoplasmic domain of XLerk, an erythropoietin-producing hepatocellular ligand SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR TYROSINE KINASES; IN-VITRO; MESODERM INDUCTION; COMMISSURAL AXONS; EPH RECEPTORS; GROWTH-FACTOR; EXPRESSION; FAMILY; GUIDANCE; SYSTEM AB The erythropoietin-producing hepatocellular (Eph) family of ligands and receptors has been implicated in the control of axon guidance and the segmental restriction of cells during embryonic development. In this report, we show that ectopic expression of XLerk, a Xenopus homologue of the murine Lerk-2 (ephrin-B1) transmembrane ligand, causes dissociation of Xenopus embryonic blastomeres by the mid-blastula transition. Moreover, a mutant that lacks the extracellular receptor binding domain can induce this phenotype. The carboxyl-terminal 19 amino acids of the cytoplasmic domain of XLerk are necessary but not sufficient to induce cellular dissociation. Basic fibroblast growth factor, but not activin, can rescue both the loss of cell adhesion and mesoderm induction in ectodermal explants expressing XLerk. Collectively, these results show that the cytoplasmic domain of XLerk has a signaling function that is important for cell adhesion, and fibroblast growth factor signaling modulates this function. C1 NCI, Lab Leukocyte Biol, Frederick Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Biochem Physiol, Frederick Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Daar, IO (reprint author), NCI, Lab Leukocyte Biol, Frederick Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Bldg 567,Room 228, Frederick, MD 21702 USA. EM daar@ncifcrf.gov RI Xu, Ren-He/M-3125-2016; OI Daar, Ira/0000-0003-2657-526X NR 50 TC 68 Z9 68 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 JAN 20 PY 1998 VL 95 IS 2 BP 576 EP 581 DI 10.1073/pnas.95.2.576 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YT462 UT WOS:000071606000027 PM 9435234 ER PT J AU Chowdhury, PS Viner, JL Beers, R Pastan, I AF Chowdhury, PS Viner, JL Beers, R Pastan, I TI Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer treatment; ovarian cancer; mesothelioma ID PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; OVARIAN CANCERS; FRAGMENTS; STABILIZATION; PROTEINS; THERAPY AB Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas, and several other types of human cancers, Because among normal tissues, mesothelin is present only on mesothelial cells, it represents a good target for antibody-mediated delivery of cytotoxic agents. In the present study mice were immunized with an eukaryotic expression vector coding for mesothelin. When high serum antibody titers were obtained, a phage display library was made from the splenic mRNA of these mice, After three rounds of panning on recombinant mesothelin, a single-chain Fv (scFv)-displaying phage was selected that bound specifically to recombinant mesothelin and mesothelin-positive cells. The scFv was used to construct an immunotoxin by genetically fusing it with a truncated mutant of Pseudomonas exotoxin A, The purified immunotoxin binds mesothelin with high affinity (Kd 11 nm), is stable for over 40 hr at 37 degrees C and is very cytotoxic to cells expressing mesothelin, It also produces regressions of tumors expressing mesothelin. This combination of selective cytotoxicity, high activity, and stability makes the immunotoxin a good candidate for development as a therapeutic agent, This work also shows that DNA immunization can be used to isolate and clone antibodies against epitopes present on human proteins in their native conformation. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 27 TC 131 Z9 136 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 JAN 20 PY 1998 VL 95 IS 2 BP 669 EP 674 DI 10.1073/pnas.95.2.669 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YT462 UT WOS:000071606000043 PM 9435250 ER PT J AU Fernandez, MP Copeland, NG Gilbert, DJ Jenkins, NA Morgan, RO AF Fernandez, MP Copeland, NG Gilbert, DJ Jenkins, NA Morgan, RO TI Mouse annexin III cDNA, genetic mapping and evolution SO GENE LA English DT Article DE chromosomal localization; gene duplication; genetic linkage map; molecular evolution; molecular sequence data; nucleotide substitution rates ID PHOSPHOLIPID-BINDING-PROTEINS; INOSITOL 1,2-CYCLIC PHOSPHATE; CHROMOSOMAL LOCALIZATION; HUMAN NEUTROPHILS; ANX3 GENE; KINASE-C; SEQUENCE; EXPRESSION; ALIGNMENT; CALCIUM AB Mouse annexin III cDNA was characterized from I.M.A.G.E. Consortium (LLNL) expressed sequence tag clones by molecular sequencing, chromosomal mapping and systematic analysis. cDNA sequences extended the known 5' and 3' untranslated regions and confirmed the location of intron 7 with respect to the human gene. The Anx3 locus mapped to the middle of mouse chromosome 5 between Areg and Fgf5. Protein-coding regions were compared with homologous annexins to establish subfamily identity, structural conservation and divergence pattern. Annexin III exhibited low functional constraint against structural change and weak phylogenetic association with known annexins. The rapid, constant divergence of human and rodent annexins III from each other and from other annexin subfamilies was used to estimate gene separation times. Phylogenetic, phenetic and structural data suggested a possible direct or indirect separation of annexin III from XI approximately 317 million years ago. (C) 1998 Elsevier Science B.V. C1 Univ Oviedo, Fac Med, Dept Biochem & Mol Biol, E-33006 Oviedo, Spain. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Univ Oviedo, Fac Med, Dept Biochem & Mol Biol, E-33006 Oviedo, Spain. EM mpff@dwarf1.quimica.uniovi.es OI Fernandez-Fernandez, Maria Pilar/0000-0001-6552-409X NR 35 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD JAN 19 PY 1998 VL 207 IS 1 BP 43 EP 51 DI 10.1016/S0378-1119(97)00602-1 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA YY459 UT WOS:000072148700006 PM 9511742 ER PT J AU Valente, P Fassina, G Melchiori, A Masiello, L Cilli, M Vacca, A Onisto, M Santi, L Stetler-Stevenson, WG Albini, A AF Valente, P Fassina, G Melchiori, A Masiello, L Cilli, M Vacca, A Onisto, M Santi, L Stetler-Stevenson, WG Albini, A TI TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-TISSUE INHIBITOR; IV COLLAGENASE; INTEGRIN ALPHA-V-BETA-3; IN-VIVO; METALLOPROTEINASES; METASTASIS; SURFACE; GROWTH; PROLIFERATION; ACTIVATION AB The matrix metalloproteinase (MMP) inhibitor TIMP-2 has a high specificity for gelatinase A/MMP-2. An imbalance between gelatinase A and TIMP-2 in favor of enzymatic activity is linked to the degradation of the extracellular matrix (ECM) associated with several physiologic and pathologic events, including angiogenesis, invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors, We transfected B16F10 murine melanoma cells, a highly invasive and metastatic cell line, with an expression vector harboring a cDNA encoding for human TIMP-2. The clones obtained were isolated and examined for TIMP-2 over-expression and changes in tumor cell phenotype. The amount of recombinant TIMP-2 produced correlated with a reduction in invasion, In an in vivo angiogenesis assay, TIMP-2-transfected clones showed reduced levels of blood vessel formation, and in vitro conditioned media from TIMP-2 transfectants showed diminished induction of endothelial cell migration and invasion. TIMP-2 over-expression limited tumor growth in vivo and neoangiogenesis when cells were injected subcutaneously in mice in the presence of Matrigel. However, TIMP-2 over-expressing clones were found to be more resistant to apoptosis than parental and control melanoma cells, while necrosis was increased. Our data confirm the role of TIMP-2 in the down-regulation of metastasis and angiogenesis but indicate a possible involvement in tumor cell survival. (C) 1998 Wiley-Liss, Inc. C1 Ist Nazl Ric Canc, CBA, I-16132 Genoa, Italy. Adv Biotechnol Ctr, Genoa, Italy. Univ Bari, Sch Med, Dept Biomed Sci & Human Oncol, Bari, Italy. Univ Padua, Inst Histol & Embryol, Padua, Italy. CNR, Ctr Studio Neurofisiol Cerebrale, Genoa, Italy. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Albini, A (reprint author), Ist Nazl Ric Canc, CBA, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 32 TC 214 Z9 224 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 19 PY 1998 VL 75 IS 2 BP 246 EP 253 DI 10.1002/(SICI)1097-0215(19980119)75:2<246::AID-IJC13>3.0.CO;2-B PG 8 WC Oncology SC Oncology GA YU948 UT WOS:000071772700013 PM 9462715 ER PT J AU Tsutsui, T Tamura, Y Yagi, E Hasegawa, K Takahashi, M Maizumi, N Yamaguchi, F Barrett, JC AF Tsutsui, T Tamura, Y Yagi, E Hasegawa, K Takahashi, M Maizumi, N Yamaguchi, F Barrett, JC TI Bisphenol-A induces cellular transformation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NEOPLASTIC TRANSFORMATION; CHROMOSOMAL-ABERRATIONS; DIETHYLSTILBESTROL; INDUCTION; MECHANISM; BINDING; TESTS AB Bisphenol-A (BP-A) is a major component of epoxy, polycarbonate and other resins. For an assessment of in vitro carcinogenicity and related activity of BP-A, the abilities of this compound to induce cellular transformation and genetic effects were examined simultaneously using the Syrian hamster embryo (SHE) cell model. Cellular growth was reduced by continuous treatment with BP-A at doses greater than or equal to 100 mu M. However, colony-forming efficiencies were not decreased significantly following treatment with up to 200 mu M BP-A for 48 hr. Morphological transformation of SHE cells was induced by treatment of cells with BP-A at 50 to 200 mu M for 48 hr. BP-A exhibited transforming activity at doses greater than or equal to 50 mu M but was less active than the benzo[a]pyrene used as a positive control. Over the dose range that resulted in cellular transformation, treatment of SHE cells with BP-A failed to induce gene mutations at the Na+/K+ ATPase locus or the hprt locus. No statistically significant numbers of chromosomal aberrations were detected in SHE cells treated with BP-A. However, treatment of cells with BP-A induced numerical chromosomal changes in the near diploid range at doses that induced cellular transformation. P-32-Postlabeling analysis revealed that exposure of cells to BP-A also elicited DNA adduct formation in a dose-dependent fashion. Our results indicate that BP-A has cell-transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity. (C) 1998 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ, Dept Pharmacol, Tokyo, Japan. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, MD C2-15, Res Triangle Pk, NC 27709 USA. NR 30 TC 80 Z9 85 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 19 PY 1998 VL 75 IS 2 BP 290 EP 294 DI 10.1002/(SICI)1097-0215(19980119)75:2<290::AID-IJC19>3.0.CO;2-H PG 5 WC Oncology SC Oncology GA YU948 UT WOS:000071772700019 PM 9462721 ER PT J AU Franzoso, G Carlson, L Poljak, L Shores, EW Epstein, S Leonardi, A Grinberg, A Tran, T Scharton-Kersten, T Anver, M Love, P Brown, K Siebenlist, U AF Franzoso, G Carlson, L Poljak, L Shores, EW Epstein, S Leonardi, A Grinberg, A Tran, T Scharton-Kersten, T Anver, M Love, P Brown, K Siebenlist, U TI Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; CANDIDATE PROTOONCOGENE BCL-3; DNA-BINDING; ONCOPROTEIN BCL-3; IMMUNE-RESPONSE; P50 HOMODIMERS; LYMPHOID MALIGNANCIES; TARGETED DISRUPTION; DENDRITIC CELLS; PRECURSOR P105 AB p52 is a subunit of nuclear factor (NF)-kappa B transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the I kappa B family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further su that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Franzoso, G (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 62 TC 307 Z9 320 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 19 PY 1998 VL 187 IS 2 BP 147 EP 159 DI 10.1084/jem.187.2.147 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YU549 UT WOS:000071729000002 PM 9432973 ER PT J AU Caumont, AS Galas, MC Vitale, N Aunis, D Bader, MF AF Caumont, AS Galas, MC Vitale, N Aunis, D Bader, MF TI Regulated exocytosis in chromaffin cells - Translocation of ARF6 stlmulates a plasma membrane-associated phospholipase D SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; PHOSPHATIDIC-ACID; G-PROTEINS; CATECHOLAMINE SECRETION; SYNTHETIC PEPTIDE; BINDING PROTEINS; CHOLERA-TOXIN; BREFELDIN-A; PC12 CELLS; ACTIVATION AB The ADP-ribosylation factor (ARF) GTP-binding proteins have been implicated in a wide range of vesicle transport and fusion steps along the secretory pathway. In chromaffin cells, ARF6 is specifically associated with the membrane of secretory chromaffin granules, Since ARF6 is an established regulator of phospholipase D (PLD), we have examined the intracellular distribution of ARF6 and PLD activity in resting and stimulated chromaffin cells. We found that stimulation of intact chromaffin cells or direct elevation of cytosolic calcium in permeabilized cells triggered the rapid translocation of ARF6 from secretory granules to the plasma membrane and the concomitant activation of PLD in the plasma membrane. To probe the existence of an ARF6-dependent PLD in chromaffin cells, we measured the PLD activity in purified plasma membranes. PLD could be activated by a nonhydrolyzable analogue of GTP and by recombinant myristoylated ARF6 and inhibited by specific anti-ARF6 antibodies, Furthermore, a synthetic myristoylated peptide corresponding to the N-terminal domain of ARF6 inhibited both PLD activity and catecholamine secretion in calcium-stimulated chromaffin cells. The possibility that ARF6 participates in the exocytotic reaction by controlling a plasma membrane-bound PLD and thereby generating fusogenic lipids at the exocytotic sites is discussed. C1 INSERM, U338, F-67084 Strasbourg, France. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20814 USA. RP Bader, MF (reprint author), INSERM, U338, 5 Rue Blaise Pascal, F-67084 Strasbourg, France. EM bader@neurochem.u-strasbg.fr RI Vitale, nicolas/G-5967-2014; Dietz-Bader, Marie-France/O-2098-2016 OI Vitale, nicolas/0000-0002-4752-4907; NR 52 TC 131 Z9 132 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 JAN 16 PY 1998 VL 273 IS 3 BP 1373 EP 1379 DI 10.1074/jbc.273.3.1373 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ670 UT WOS:000071411500018 PM 9430671 ER PT J AU Kim, J Lin, JJ Xu, RH Kung, HF AF Kim, J Lin, JJ Xu, RH Kung, HF TI Mesoderm induction by heterodimeric AP-1 (c-Jun and c-Fos) and its involvement in mesoderm formation through the embryonic fibroblast growth factor Xbra autocatalytic loop during the early development of Xenopus embryos SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE; NULL MUTATION; REQUIRES FGF; EXPRESSION; ACTIVIN; ACTIVATION; DORSAL; SPECIFICATION; GASTRULATION; SIGNALS AB We have previously demonstrated the involvement of AP-1/Jun in fibroblast growth factor (FGF) signaling by loss-of-function assay (Dong, Z., Xu, R.-H., Kim, J., Zhan, S.-N., Ma, W.-Y., Colburn, N. H., and Kung, H. (1996) J. Biol, Chem. 271, 9942-9946), Further investigations by gain-of-function are reported in this study, AP-1 transactivation activity was increased by the treatment of animal cap explants with FGF, Ectopic overexpression of two components of AP-1 (c-jun and c-fos together, but not alone) produced posteriorized embryos and induced mesoderm formation in animal cap explants, indicating that both AP-1 heterodimers are required for mesoderm induction, Since Ras/AP-1 functions downstream of FGF signaling, we then tested the involvement of Ras/AP-1 in mesoderm maintenance mediated by embryonic FGF/ Xbra using dominant-negative mutants, Mesoderm maintenance mediated by embryonic FGF/Xbra was blocked by dominant-negative mutants of Ras/AP-1, and AP-1 enhanced the expression of Xbra, Further studies demonstrated the inhibition of Ras/AP-1-mediated mesoderm formation by dominant-negative mutants of the FGF receptor and Xbra, These results indicate that Ras/ AP-1 and FGF/Xbra signals are involved in the mesoderm maintenance machinery and mesoderm formation through the synergistic action of the diversified signal pathways derived from the FGF/Xbra autocatalytic loop. C1 NCI, Lab Biochem Physiol, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res & Support Program, Frederick, MD 21702 USA. RP Kung, HF (reprint author), NCI, Lab Biochem Physiol, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. EM Kungh@mail.ncifcrf.gov RI Xu, Ren-He/M-3125-2016 NR 45 TC 14 Z9 17 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 JAN 16 PY 1998 VL 273 IS 3 BP 1542 EP 1550 DI 10.1074/jbc.273.3.1542 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ670 UT WOS:000071411500041 PM 9430694 ER PT J AU Park, MH Joe, YA Kang, KR AF Park, MH Joe, YA Kang, KR TI Deoxyhypusine synthase activity is essential for cell viability in the yeast Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC INITIATION FACTOR-5A; PROTEIN-SYNTHESIS; HYPUSINE MODIFICATION; SHUTTLE VECTORS; AEROBIC GROWTH; FACTOR EIF-5A; RAT TESTIS; HELA-CELLS; PURIFICATION; GENE AB Deoxyhypusine synthase catalyzes the first step in the posttranslational synthesis of an unusual amino acid, hypusine (N-epsilon-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic translation initiation factor 5A (eIF 5A) precursor protein, The null mutation in the single copy gene, gamma DHS, encoding deoxyhypusine synthase results in the loss of viability in the yeast Saccharomyces cerevisiae. Upon depletion of deoxyhypusine synthase, and consequently of eIF-5A, cessation of growth was accompanied by a marked enlargement of cells, suggesting a defect in cell cycle progression or in cell division. Two residues of the yeast enzyme, Lys(308) and Lys(350), corresponding to Lys(287) and Lys(329), respectively, known to be critical for the activity of the human enzyme, were targeted for site-directed mutagenesis, The chromosomal gamma dhs null mutation was complemented by the plasmid-borne gamma DHS wild-type gene, but not by mutated genes encoding inactive proteins, including that with Lys(350) --> Arg substitution or with substitutions at both Lys(308) and Lys(350). The mutated gene gamma dhs(K308R) encoding a protein with diminished activities (<1% of wild type) could support growth but only to a very limited extent, These findings provide strong evidence that the hypusine modification is indeed essential for the survival of S. cerevisiae and imply a vital function for eIF-5A in all eukaryotes. 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. EM mpark@yoda.nidr.nih.gov NR 43 TC 89 Z9 98 U1 0 U2 5 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 JAN 16 PY 1998 VL 273 IS 3 BP 1677 EP 1683 DI 10.1074/jbc.273.3.1677 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ670 UT WOS:000071411500059 PM 9430712 ER PT J AU Wlodawer, A Davies, D Petsko, G Rossmann, M Olson, A Sussman, JL AF Wlodawer, A Davies, D Petsko, G Rossmann, M Olson, A Sussman, JL TI Immediate release of crystallographic data: A proposal SO SCIENCE LA English DT Letter C1 NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIDDKD, Sect Mol Struct, NIH, Bethesda, MD 20892 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Brookhaven Natl Lab, Prot Data Bank, Upton, NY 11973 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Wlodawer, A (reprint author), NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 16 PY 1998 VL 279 IS 5349 BP 306 EP 307 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YT158 UT WOS:000071570800008 PM 9454319 ER PT J AU Winkler, C Modi, W Smith, MW Nelson, GW Wu, XY Carrington, M Dean, M Honjo, T Tashiro, K Yabe, D Buchbinder, S Vittinghoff, E Goedert, JJ O'Brien, TR Jacobson, LP Detels, R Donfield, S Willoughby, A Gomperts, E Vlahov, D Phair, J O'Brien, SJ AF Winkler, C Modi, W Smith, MW Nelson, GW Wu, XY Carrington, M Dean, M Honjo, T Tashiro, K Yabe, D Buchbinder, S Vittinghoff, E Goedert, JJ O'Brien, TR Jacobson, LP Detels, R Donfield, S Willoughby, A Gomperts, E Vlahov, D Phair, J O'Brien, SJ CA ALIVE Study Hemophilia Growth Dev Study Multicenter AIDS Cohort Study Multicenter Hemophilia Cohort Study San Francisco City Cohort TI Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; TYPE-1 INFECTION; PROGRESSION; RECEPTORS; RESISTANCE; INDIVIDUALS; COFACTOR; DISEASE; ENTRY AB Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. Kyoto Univ, Dept Med Chem, Kyoto 606, Japan. Kyoto Univ, Ctr Mol Biol & Genet, Kyoto 606, Japan. Dept Publ Hlth, AIDS Off, San Francisco, CA 94102 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, CAMACS, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Rho Inc, Chapel Hill, NC 27514 USA. NICHHD, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Northwestern Univ, Sch Med, Comprehens AIDS Ctr, Chicago, IL 60611 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. RI Smith, Michael/B-5341-2012; Dean, Michael/G-8172-2012; Honjo, Tasuku/N-4470-2016; OI Dean, Michael/0000-0003-2234-0631; Yabe, Daisuke/0000-0002-5334-7687 NR 62 TC 571 Z9 596 U1 3 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 16 PY 1998 VL 279 IS 5349 BP 389 EP 393 DI 10.1126/science.279.5349.389 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YT158 UT WOS:000071570800048 PM 9430590 ER PT J AU Kohler, DR Montello, MJ Green, L Huntley, C High, JL Fallavollita, A Goldspiel, BR AF Kohler, DR Montello, MJ Green, L Huntley, C High, JL Fallavollita, A Goldspiel, BR TI Standardizing the expression and nomenclature of cancer treatment regimens SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE American Society of Health-System Pharmacists; antineoplastic agents; dosage schedules; errors, medication; forms; labeling; medication orders; neoplasms; nomenclature; organizations; pharmacists, institutional; protocols; standards ID CHEMOTHERAPY; ERRORS AB Guidelines for describing cancer chemotherapy regimens in all aspects of drug development, including treatment protocols, order forms, and product labels, are proposed. To complement the approaches to reducing medication errors that have been recommended by ASHP and others, pharmacists at the National Institutes of Health and the National Cancer Institute, with the input of oncology pharmacists from diverse areas of practice, developed guidelines for expressing chemotherapy dosage schedules and treatment regimens. The guidelines present standards that are broadly applicable and can be adopted by other institutions. Clear and unambiguous expression of all medication orders and consistency of treatment descriptions are suggested. Written treatment plans and orders should contain enough information to allow health care providers from diverse disciplines to compare them with published treatment descriptions and investigational protocols and must therefore include planned dosages and schedules expressed in patient-specific units. In general, drug dosages should be expressed as the amount of drug administered from a single container. When ordering drugs that are part of complex or combination-drug regimens, prescribers should write as many of the orders at one time as is possible, so that continuity might be preserved. Standard rules are proposed for describing chemotherapy regimens. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NCI, Protocol & Informat Off, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. Amgen Inc, Profess Serv, Thousand Oaks, CA 91320 USA. NCI, Drug Management & Authorizat Sect, Pharmaceut Management Branch, CTEP,DCTD,NIH, Bethesda, MD 20892 USA. RP Kohler, DR (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bldg 10,Room IN-257,10 Ctr Dr,MSC-1196, Bethesda, MD 20892 USA. NR 11 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 15 PY 1998 VL 55 IS 2 BP 137 EP 144 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YV742 UT WOS:000071858200011 PM 9465977 ER PT J AU Papanicolaou, DA Wilder, RL Manolagas, SC Chrousos, GP AF Papanicolaou, DA Wilder, RL Manolagas, SC Chrousos, GP TI The pathophysiologic roles of interleukin-6 in human disease SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PITUITARY-ADRENAL AXIS; C-REACTIVE PROTEIN; SYSTEMIC LUPUS-ERYTHEMATOSUS; SOLUBLE IL-6 RECEPTOR; ACUTE-PHASE PROTEINS; ANTI-INTERLEUKIN-6 MONOCLONAL-ANTIBODY; CORTICOTROPIN-RELEASING HORMONE; STIMULATORY FACTOR-II; NF-KAPPA-B; RHEUMATOID-ARTHRITIS AB Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Dept Internal Med, Div Endocrinol Metab, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Internal Med, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. RP Papanicolaou, DA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 116 TC 758 Z9 804 U1 0 U2 21 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 JAN 15 PY 1998 VL 128 IS 2 BP 127 EP 137 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA YR200 UT WOS:000071470800008 PM 9441573 ER PT J AU Hausser, H Schonherr, E Muller, M Liszio, C Bin, Z Fisher, LW Kresse, H AF Hausser, H Schonherr, E Muller, M Liszio, C Bin, Z Fisher, LW Kresse, H TI Receptor-mediated endocytosis of decorin: Involvement of leucine-rich repeat structures SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE biglycan; endocytosis receptor; core protein; clearance; proteoglycan ID DERMATAN SULFATE PROTEOGLYCAN; COLLAGEN FIBRILLOGENESIS; I COLLAGEN; PROTEIN; EXPRESSION; INTERFERENCE; FIBROBLASTS; FIBRONECTIN; INHIBITOR; ADHESION AB Decorin, a small dermatan sulfate proteoglycan, is characterized by a core protein with central leucine-rich repeat structures and a single glycosaminoglycan chain. It is catabolized by receptor-mediated uptake and subsequent intralysosomal degradation. In the present study, the localization of the receptor binding site(s) along the core protein was investigated. Various recombinant decorin fragments were consistently able to inhibit the endocytosis of wild-type decorin. The most potent inhibitory peptides were those which encompassed the central Leu125-Val230 region, i.e., the fifth to eighth leucine-rich repeat, or at least a part of it. The peptide Leu125-Val230 bound directly to the 51-kDa endocytosis receptor, and Fab fragments of antibodies against this peptide inhibited the endocytosis of decorin in a dose-dependent manner. Decorin constructs expressed in human 293 cells and comprising the full-length coding region or lacking sequences N- and/or C-terminally of the Leu125-Val230 region were all endocytosed with similar clearance rates. These data suggest that the N- and C-terminal domains of the core protein are not required for endocytosis. The receptor binding site is rather represented by contiguous leucine-rich repeat structures of the central part of the core protein. This conclusion is supported by competition experiments with biglycan, a structurally related small proteoglycan. (C) 1998 Academic Press. C1 Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster, Germany. NIDR, NIH, Bethesda, MD 20892 USA. RP Hausser, H (reprint author), Univ Munster, Inst Physiol Chem & Pathobiochem, Waldeyerstr 15, D-48149 Munster, Germany. NR 38 TC 32 Z9 32 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 JAN 15 PY 1998 VL 349 IS 2 BP 363 EP 370 DI 10.1006/abbi.1997.0471 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YT028 UT WOS:000071556800020 PM 9448726 ER PT J AU Zaher, H Yang, TJ Gelboin, HV FernandezSalguero, P Gonzalez, FJ AF Zaher, H Yang, TJ Gelboin, HV FernandezSalguero, P Gonzalez, FJ TI Effect of phenobarbital on hepatic CYP1A1 and CYP1A2 in the Ahr-Null mouse SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Ahr-null mouse; CYP1A1; CYP1A2; phenobarbital; regulation ID MESSENGER-RNA; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; RAT HEPATOCYTES; INDUCTION; RECEPTOR; CYTOCHROME-P450; LIVER; MICE; METABOLISM AB Studies have suggested that phenobarbital (PB) induces members of the CYP1A subfamily by both transcriptional and post-transcriptional mechanisms. Using the Ahr-/- mice, we examined the induction of CYP1A1 and CYP1A2 by PB. CYP1A2 mRNA and protein were induced by PB in the null mice, suggesting that CYP1A2 is regulated by PB by a mechanism independent of the aryl hydrocarbon receptor (AHR). In contrast, the regulation oi CYP1A1 is highly dependent on the AHR. (C) 1998 Elsevier Science Inc. C1 NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Zaher, H (reprint author), NCI,LAB METAB,NIH,BLDG 37,ROOM 3E-24,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 25 TC 26 Z9 26 U1 0 U2 0 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 JAN 15 PY 1998 VL 55 IS 2 BP 235 EP 238 DI 10.1016/S0006-2952(97)00476-0 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YK015 UT WOS:A1998YK01500016 PM 9448747 ER PT J AU van den Bree, MBM Johnson, EO Neale, MC Svikis, DS McGue, M Pickens, RW AF van den Bree, MBM Johnson, EO Neale, MC Svikis, DS McGue, M Pickens, RW TI Genetic analysis of diagnostic systems of alcoholism in males SO BIOLOGICAL PSYCHIATRY LA English DT Article DE diagnostic systems of alcoholism; genetic influences; environmental influences; male subjects; treatment sample; threshold modeling ID II ALCOHOLISM; INDICATORS; MEN; INHERITANCE; INDIVIDUALS; SEVERITY; ADOPTION; TRAITS; ABUSE; TWIN AB Background: Research into genes involved in alcoholism could benefit from use of diagnostic systems most sensitive to detecting generic influences. In this study, heritable influences were estimated in a single twin sample with commonly used criteria for alcoholism. Methods: Male twin probands ascertained through alcohol and drug abuse treatment programs and their same-sex cotwins (54 monozygotic and 65 dizygotic pairs) were diagnosed independently by DSM-III (alcohol dependence and alcohol abuse and/or dependence), Feighner (probable and definite alcoholism), and Cloninger (type I and type 2 alcoholism) systems. Using univariate structural equation modeling, heritability was estimated for each diagnostic system. Results: The highest heritability estimates were obtained for Feighner probable alcoholism (h(2) = .63), Cloninger type 2 alcoholism (h(2) = .54), and DSM-III alcohol dependence (h(2) = .52). Conclusions: Certain diagnostic systems appear to have greater sensitivity for detecting genetic influence and may therefore be more appropriate for use in molecular genetic studies attempting to find genes for alcoholism. Published 1998 Society of Biological Psychiatry. C1 NIDA, Addict Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Richmond, VA 23298 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP van den Bree, MBM (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. RI Neale, Michael/B-1418-2008; turton, miranda/F-4682-2011 NR 39 TC 31 Z9 31 U1 1 U2 3 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 JAN 15 PY 1998 VL 43 IS 2 BP 139 EP 145 DI 10.1016/S0006-3223(97)00225-4 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YX910 UT WOS:000072093000007 PM 9474446 ER PT J AU Parker, BW Kaur, G Nieves-Neira, W Taimi, M Kohlhagen, G Shimizu, T Losiewicz, MD Pommier, Y Sausville, EA Senderowicz, AM AF Parker, BW Kaur, G Nieves-Neira, W Taimi, M Kohlhagen, G Shimizu, T Losiewicz, MD Pommier, Y Sausville, EA Senderowicz, AM TI Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol SO BLOOD LA English DT Article ID DNA TOPOISOMERASE-I; CYCLIN-DEPENDENT KINASES; BREAST-CARCINOMA CELLS; HL-60 CELLS; EARLY EVENTS; G(1) ARREST; DEATH; INHIBITION; ACTIVATION; GROWTH AB Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4:120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bar protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority. (C) 1998 by The American Society of Hematology. C1 NCI, DTP Clin Trials Unit, Med Branch,Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Biol Chem Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), NCI, DTP Clin Trials Unit, Med Branch,Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Bldg 10,Room 6N113, Bethesda, MD 20892 USA. NR 43 TC 188 Z9 190 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1998 VL 91 IS 2 BP 458 EP 465 PG 8 WC Hematology SC Hematology GA YQ799 UT WOS:000071424400010 PM 9427698 ER PT J AU Nacheva, EP Grace, CD Bittner, M Ledbetter, DH Jenkins, RB Green, AR AF Nacheva, EP Grace, CD Bittner, M Ledbetter, DH Jenkins, RB Green, AR TI Comparative genomic hybridization: A comparison with molecular and cytogenetic analysis SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID SEQUENCE COPY NUMBER; GLIOMA CELL-LINES; MYELOPROLIFERATIVE DISORDERS; MYELODYSPLASTIC SYNDROMES; QUANTITATIVE-ANALYSIS; IMAGE-ANALYSIS; 20Q DELETIONS; DNA-SEQUENCES; SOLID TUMORS; LOSSES AB Comparative genomic hybridization (CGH) is a powerful technique for detecting copy number changes throughout the genome. We describe the development of a versatile image analysis program for CGH studies. Several methods for the production of metaphases which give optimum hybridization signals have also been assessed. CGH analysis was performed on DNA samples from several different and clinically relevant specimens: amniotic fluid cells trisomic for a single chromosome, lymphoblastoid cell lines with abnormalities involving single chromosome bands, malignant cell lines and biopsy material from primary ovarian carcinomas. The results were compared with those derived from G-banding, chromosome painting, and molecular genetic techniques. Our data demonstrate that CGH was able to detect a wide range of quantitative genetic alterations including duplication or deletion of single chromosome bands. CGH analysis also indicated the presence of genetic abnormalities that were not detected by/other cytogenetic or molecular approaches. Moreover, our CGH methodology allowed the ready comparison of CGH results from different tumors, a process which greatly facilitated identification of shared genetic changes. (C) Elsevier Science Inc., 1998. C1 Addenbrookes NHS Trust Hosp, Dept Haematol, Cambridge, England. Digital Sci Ltd, Cambridge, England. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. RP Nacheva, EP (reprint author), Univ Cambridge, Ctr Mrc, Dept Haematol, Hills Rd, Cambridge CB2 2QH, England. NR 28 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN 15 PY 1998 VL 100 IS 2 BP 93 EP 105 DI 10.1016/S0165-4608(97)00021-6 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YN102 UT WOS:000071133300001 PM 9428351 ER PT J AU Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Takeda, K Ferrans, VJ AF Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Takeda, K Ferrans, VJ TI Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity SO CANCER RESEARCH LA English DT Article AB The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulative doses of doxorubicin (7 mg/kg) that induced only minimal histological alterations in myocytes. Concentrations of cTnT were further elevated, coincident with reduced immunohistochemical staining, in SHRs given 10-12 mg/kg doxorubicin. Thus, monitoring serum levels of cTnT can detect doxorubicin-induced myocyte damage in SHR and may prove useful for the noninvasive evaluation of this toxicity in humans. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Laurel, MD 20708 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Div Pediat Cardiol, Rochester, NY 14642 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20852 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 80 Z9 83 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 JAN 15 PY 1998 VL 58 IS 2 BP 195 EP 197 PG 3 WC Oncology SC Oncology GA YR421 UT WOS:000071493600003 PM 9443390 ER PT J AU Shen, DW Pastan, I Gottesman, MM AF Shen, DW Pastan, I Gottesman, MM TI Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins SO CANCER RESEARCH LA English DT Article ID HUMAN TUMOR-CELLS; OVARIAN-CARCINOMA CELLS; NATURAL PRODUCT DRUGS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; KB CELLS; LUNG-CANCER; ACQUIRED-RESISTANCE; GENE-EXPRESSION; ARSENITE AB Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as sodium arsenite, sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, (3)[H]MTX, As-73(3+), and As-73(5+) was found in both cisplatin-resistant cell lines. Anal ysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of M-r 230,000 and M-r 48,000 for As-73(3+) and M-r 190,000 for As-73(5+) were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at M-r 36,000 that binds to As-73(3+) was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B22,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 64 TC 82 Z9 83 U1 1 U2 2 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 JAN 15 PY 1998 VL 58 IS 2 BP 268 EP 275 PG 8 WC Oncology SC Oncology GA YR421 UT WOS:000071493600017 PM 9443404 ER PT J AU Ambs, S Merriam, WG Bennett, WP Felley-Bosco, E Ogunfusika, MO Oser, SM Klein, S Shields, PG Billiar, TR Harris, CC AF Ambs, S Merriam, WG Bennett, WP Felley-Bosco, E Ogunfusika, MO Oser, SM Klein, S Shields, PG Billiar, TR Harris, CC TI Frequent nitric oxide synthase-2 expression in human colon adenomas: Implication for tumor angiogenesis and colon cancer progression SO CANCER RESEARCH LA English DT Article ID HUMAN COLORECTAL-CANCER; DNA-DAMAGE; IN-VIVO; MESSENGER-RNA; P53; CELLS; PEROXYNITRITE; INHIBITION; NITRATE; PROTEIN AB An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors, This observation suggests a pathobiological role of tumor-associated NO production, Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression, Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues), Only low levels were found in the surrounding normal tissue, NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung, NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01), Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein hands at M-r 125,000-M-r 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody, However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation, Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ. C1 Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37 Room 2C05,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM Curtis-Harris@nih.gov RI Shields, Peter/I-1644-2012; Felley-Bosco, Emanuela/E-7484-2017 OI Felley-Bosco, Emanuela/0000-0002-3408-0294 NR 71 TC 373 Z9 397 U1 0 U2 6 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 JAN 15 PY 1998 VL 58 IS 2 BP 334 EP 341 PG 8 WC Oncology SC Oncology GA YR421 UT WOS:000071493600027 PM 9443414 ER PT J AU Saitoh, H Sparrow, DB Shiomi, T Pu, RT Nishimoto, T Mohun, TJ Dasso, M AF Saitoh, H Sparrow, DB Shiomi, T Pu, RT Nishimoto, T Mohun, TJ Dasso, M TI Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2 SO CURRENT BIOLOGY LA English DT Article ID UBIQUITIN AB The yeast UBC9 gene encodes a protein with homology to the E2 ubiquitin-conjugating enzymes that mediate the attachment of ubiquitin to substrate proteins [1], Depletion of Ubc9p arrests cells in G2 or early M phase and stabilizes B-type cyclins [1]. p18(Ubc9), the Xenopus homolog of Ubc9p, associates specifically with p88(RanGAP1) and p340(RanBP2) [2]. Ran-binding protein 2 (p340(RanBP2)) is a nuclear pore protein [3,4], and p88(RanGAP1) is a modified form of RanGAP1, a GTPase-activating protein for the small GTPase Ran [2]. It has recently been shown that mammalian RanGAP1 can be conjugated with SUMO-1, a small ubiquitin-related modifier [5-7], and that SUMO-1 conjugation promotes RanGAP1's interaction with RanBP2 [2,5,6]. Here we show that p18(Ubc9) acts as an E2-like enzyme for SUMO-1 conjugation, but not for ubiquitin conjugation. This suggests that the SUMO-1 conjugation pathway is biochemically similar to the ubiquitin conjugation pathway but uses a distinct set of enzymes and regulatory mechanisms. We also show that p18(Ubc9) interacts specifically with the internal repeat domain of RanBP2, which is a substrate for SUMO-1 conjugation in Xenopus egg extracts. C1 NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Dev Biol, London NW7 1AA, England. Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 812, Japan. RP Dasso, M (reprint author), NICHD, Mol Embryol Lab, NIH, Bldg 18,Room 106, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov RI Sparrow, Duncan/B-3994-2008; OI Sparrow, Duncan/0000-0002-1141-6613; Dasso, Mary/0000-0002-5410-1371 NR 11 TC 149 Z9 151 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 15 PY 1998 VL 8 IS 2 BP 121 EP 124 DI 10.1016/S0960-9822(98)70044-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR236 UT WOS:000071474600022 PM 9427648 ER PT J AU Loh, YP AF Loh, YP TI Protein secretion: Puzzling receptors SO CURRENT BIOLOGY LA English DT Letter C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49, Bethesda, MD 20892 USA. NR 5 TC 7 Z9 7 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 15 PY 1998 VL 8 IS 2 BP R41 EP R41 DI 10.1016/S0960-9822(98)70029-6 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR236 UT WOS:000071474600006 PM 9427651 ER PT J AU Wikstrom, L Johansson, C Salto, C Barlow, C Barros, AC Baas, F Forrest, D Thoren, P Vennstrom, B AF Wikstrom, L Johansson, C Salto, C Barlow, C Barros, AC Baas, F Forrest, D Thoren, P Vennstrom, B TI Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1 SO EMBO JOURNAL LA English DT Article DE bradycardia; hypothermia; thyroid hormone ID MESSENGER-RNA; RESISTANCE; BETA; PROTEIN; GENE; THERMOGENESIS; DELETION; TISSUE AB Thyroid hormone, acting through several nuclear hormone receptors, plays important roles in thermogenesis, lipogenesis and maturation of the neonatal brain, The receptor specificity for mediating these effects is largely unknown, and to determine this we developed mice lacking the thyroid hormone receptor TR alpha 1, The mice have an average heart rate 20% lower than that of control animals, both under normal conditions and after thyroid hormone stimulation, Electrocardiograms show that the mice also have prolonged QRS-and QT(end)-durations. The mice have a body temperature 0.5 degrees C lower than normal and exhibit a mild hypothyroidism, whereas their overall behavior and reproduction are normal. The results identify specific and important roles for TR alpha 1 in regulation of tightly controlled physiological functions, such as cardiac pacemaking, ventricular repolarisation and control of body temperature. C1 Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. Karolinska Inst, Dept Physiol, S-17177 Stockholm, Sweden. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. NIH, Lab Genet Dis Res, Bethesda, MD 20892 USA. RP Vennstrom, B (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. EM bjorn.vennstrom@cmb.ki.se RI Baas, Frank/F-9574-2010 OI Baas, Frank/0000-0003-3912-5428 NR 28 TC 304 Z9 309 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 15 PY 1998 VL 17 IS 2 BP 455 EP 461 DI 10.1093/emboj/17.2.455 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YV120 UT WOS:000071791400013 PM 9430637 ER PT J AU Wong, JM Patterton, D Imhof, A Guschin, D Shi, YB Wolffe, AP AF Wong, JM Patterton, D Imhof, A Guschin, D Shi, YB Wolffe, AP TI Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylase SO EMBO JOURNAL LA English DT Review DE chromatin disruption; histone acetylation; nuclear receptor; transcription factor acetylation; transcriptional control ID ACTIVATION FUNCTION AF-2; YEAST ALPHA-2 REPRESSOR; RETINOIC ACID RECEPTOR; TUMOR VIRUS PROMOTER; XENOPUS-LAEVIS; SACCHAROMYCES-CEREVISIAE; NUCLEAR RECEPTORS; NUCLEOSOMAL DNA; PHO5 PROMOTER; IN-VIVO AB Histone deacetylase and chromatin assembly contribute to the control of transcription of the Xenopus TR beta A gene promoter by the heterodimer of Xenopus thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR), Addition of the histone deacetylase inhibitor Trichostatin A (TSA) relieves repression of transcription due to chromatin assembly following microinjection of templates into Xenopus oocyte nuclei, and eliminates regulation of transcription by TR-RXR. Expression of Xenopus RPD3p, the catalytic subunit of histone deacetylase, represses the TR beta A promoter, but only after efficient assembly of the template into nucleosomes, In contrast, the unliganded TR-RXR represses templates only partially assembled into nucleosomes; addition of TSA also relieves this transcriptional repression, This result indicates the distinct requirements for chromatin assembly in mediating transcriptional repression by the deacetylase alone, compared with those needed in the presence of unliganded TR-RXR. In addition, whereas hormone-bound TR-RXR targets chromatin disruption as assayed through changes in minichromosome topology and loss of a regular nucleosomal ladder on micrococcal nuclease digestion, addition of TSA relieves transcriptional repression but does not disrupt chromatin, Thus, TR-RXR can facilitate transcriptional repression in the absence of hormone through mechanisms in addition to recruitment of deacetylase, and disrupts chromatin structure through mechanisms in addition to the inhibition or release of deacetylase. C1 NICHHD, Mol Biol Sect, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Mol Morphogenesis, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Biol Sect, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov NR 116 TC 130 Z9 132 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 JAN 15 PY 1998 VL 17 IS 2 BP 520 EP 534 DI 10.1093/emboj/17.2.520 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YV120 UT WOS:000071791400019 PM 9430643 ER PT J AU Ramsden, DA Gellert, M AF Ramsden, DA Gellert, M TI Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks SO EMBO JOURNAL LA English DT Article DE DNA repair; DNA-PK; Ku70; Ku86; V(D)J recombination ID V(D)J RECOMBINATION; MUTANTS; MECHANISMS; ANTIGEN; KINASE; CELLS; PK AB Ku protein binds to DNA ends and is a cofactor for the DNA-dependent protein kinase, Both of these components are involved in DNA double-strand break repair, but it has not been clear if they function indirectly, by sensing DNA damage and activating other factors, or if they are more directly involved in the processing and rejoining of DNA breaks, We demonstrate that intermolecular ligation of DNA fragments is highly dependent on Ku under conditions designed to mimic those existing in the cell. This effect of Ku is specific to eukaryotic DNA ligases, Ku protein, therefore, has an activity consistent with a direct role in rejoining DNA breaks and independent of DNA-dependent protein kinase. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 241, Bethesda, MD 20892 USA. NR 37 TC 220 Z9 225 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 15 PY 1998 VL 17 IS 2 BP 609 EP 614 DI 10.1093/emboj/17.2.609 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YV120 UT WOS:000071791400027 PM 9430651 ER PT J AU Kambadur, R Koizumi, K Stivers, C Nagle, J Poole, SJ Odenwald, WF AF Kambadur, R Koizumi, K Stivers, C Nagle, J Poole, SJ Odenwald, WF TI Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS SO GENES & DEVELOPMENT LA English DT Article DE castor; hunchback; zinc finger proteins; CNS POU gene regulation ID CENTRAL-NERVOUS-SYSTEM; CELL FATE SPECIFICATION; TRANSCRIPTION FACTOR; CEREBRAL-CORTEX; DOMAIN PROTEIN; FINGER PROTEIN; NEUROBLAST LINEAGES; CRYSTAL-STRUCTURE; DNA COMPLEX; MITI-MERE AB POU transcription factors participate in cell-identity decisions during nervous system development, yet little is known about the regulatory networks controlling their expression, We report all known Drosophila POU genes require castor (cas) for correct CNS expression. drifter and I-POU depend on cas for full expression, whereas pdm-1 and pdm-2 are negatively regulated. cas encodes a zinc finger protein that shares DNA-binding specificity with another pdm repressor: the gap segmentation gene regulator Hunchback (Hb). Our studies reveal that the embryonic CNS contains sequentially generated neuroblast sublineages that can be distinguished by their expression of either Hb, Pdm-1, or Cas. Hb and Cas may directly silence pdm expression in early and late developing sublineages, given that pdm-1 cis-regulatory DNA contains greater than or equal to 32 Hb/Cas-binding sites and its enhancer(s) are ectopically activated in cas(-) neuroblasts. In addition, the targeted misexpression of Cas in all neuroblast lineages reduces Pdm-1 expression without altering Hb expression. By ensuring correct POU gene expression boundaries, hb and cas maintain temporal subdivisions in the cell-identity circuitry controlling CNS development. C1 NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, DNA Sequencing Facil, NIH, Bethesda, MD 20892 USA. Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. RP Odenwald, WF (reprint author), NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 70 TC 159 Z9 160 U1 1 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 JAN 15 PY 1998 VL 12 IS 2 BP 246 EP 260 DI 10.1101/gad.12.2.246 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YX945 UT WOS:000072096400010 PM 9436984 ER PT J AU Rossi, DL Hardiman, G Copeland, NG Gilbert, DJ Jenkins, N Zlotnik, A Bazan, JF AF Rossi, DL Hardiman, G Copeland, NG Gilbert, DJ Jenkins, N Zlotnik, A Bazan, JF TI Cloning and characterization of a new type of mouse chemokine SO GENOMICS LA English DT Article ID ALZHEIMERS-DISEASE; ADHESION MOLECULES; BETA-CHEMOKINES; EXPRESSION; PROTEOGLYCANS; FAMILY; LOCALIZATION; LYMPHOTACTIN; ALIGNMENT; CYTOKINES AB We report here the identification and characterization of the mouse homologue of a human CX3C chemokine described by F. Bazan et al. (1997, Nature 385, 640-644). Termed fractalkine, this molecule constitutes a fourth or delta chemokine structural type that displays a novel CX3C sequence fingerprint. Distinct from the alpha, beta, or gamma chemokine families, the polypeptide chain of CX3C predicts a 373-amino-acid type I transmembrane glycoprotein with the chemokine domain resting on top of an extended mucin-like stalk. Comparison of the mouse and human protein chains shows a high degree of conservation in all the globular segments with the exception of the stalk portion. The striking identity of an amino acid stretch encompassing a putative juxtamembrane cleavage site suggests the evolutionary conservation of both membrane-bound and processed CX3C forms. Northern analysis reveals the presence of mouse CX3C mRNA in heart, brain, lung, kidney, skeletal muscle, and testis tissues. The mouse CX3C gene was further localized to the central region of chromosome 8 by interspecific backcross mapping; a related locus was detected on chromosome 11. The novel location of this gene from other chemokine gene clusters adds to the notion that CX3C is a fundamentally new class of chemokine. (C) 1998 Academic Press. C1 DNAX Res Inst Mol & Cellular Biol Inc, Dept Biol Mol, Palo Alto, CA 94304 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunobiol, Palo Alto, CA 94304 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Bazan, JF (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, Dept Biol Mol, Palo Alto, CA 94304 USA. RI Bazan, J. Fernando/B-4562-2010; Zlotnik, Albert/C-3791-2011 NR 34 TC 56 Z9 59 U1 0 U2 3 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 JAN 15 PY 1998 VL 47 IS 2 BP 163 EP 170 DI 10.1006/geno.1997.5058 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YW034 UT WOS:000071889000002 PM 9479488 ER PT J AU Yoshikawa, T Sanders, AR Esterling, LE Detera-Wadleigh, SD AF Yoshikawa, T Sanders, AR Esterling, LE Detera-Wadleigh, SD TI Multiple transcriptional variants and RNA editing in C18orf1, a novel gene with LDLRA and transmembrane domains on 18p11.2 SO GENOMICS LA English DT Article ID DENSITY LIPOPROTEIN RECEPTOR; LIGAND-BINDING DOMAIN; MESSENGER-RNA; SEQUENCES; PROTEIN; DNA; POLYADENYLATION; EXPRESSION; ELEMENTS; REGION AB C18orf1 is a novel brain-expressed transcript, mapping to 18p11.2. Upon further characterization, we found multiple and differentially expressed transcriptional variants. Cl8orf1 alpha 1, an 8.5-kb transcript, was predicted to code for a 306-amino-acid protein and a 7.1-kb 3'-untranslated region (UTR). This variant was encoded by at least six exons. Alternative transcripts included alpha 2, identical to alpha 1 but missing 18 residues, and N-terminal-truncated variants termed beta 1 and beta 2. A motif search suggested the presence of a transmembrane domain in both alpha and beta and a low-density lipoprotein receptor class A (LDLRA) domain in the alpha-specific N-terminal. In LDLR, LDLRA has been shown to be involved in binding Ca2+ and LDL, raising the possibility that C18orf1 might bind Ca2+ and an unknown ligand. We also present evidence of RNA editing in the 5'-UTR of beta 2, the first demonstration 5'-UTR. C1 NIMH, Clin Neurogenet Branch, Unit Gene Mapping & Express, NIH, Bethesda, MD 20892 USA. RP Detera-Wadleigh, SD (reprint author), NIMH, Clin Neurogenet Branch, Unit Gene Mapping & Express, NIH, Bldg 10,Room 3N218, Bethesda, MD 20892 USA. NR 34 TC 13 Z9 14 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 JAN 15 PY 1998 VL 47 IS 2 BP 246 EP 257 DI 10.1006/geno.1997.5118 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YW034 UT WOS:000071889000011 PM 9479497 ER PT J AU Lee, CGL Gottesman, MM AF Lee, CGL Gottesman, MM TI HIV-1 protease inhibitors and the MDR1 multidrug transporter SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID P-GLYCOPROTEIN; RESISTANCE; BLOOD C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lee, CGL (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 13 TC 55 Z9 55 U1 0 U2 2 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 JAN 15 PY 1998 VL 101 IS 2 BP 287 EP 288 DI 10.1172/JCI2575 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YT986 UT WOS:000071668000001 PM 9435298 ER PT J AU Zheng, LX Trageser, CL Willerford, DM Lenardo, MJ AF Zheng, LX Trageser, CL Willerford, DM Lenardo, MJ TI T cell growth cytokines cause the superinduction of molecules mediating antigen-induced T lymphocyte death SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED APOPTOSIS; ANERGY INDUCTION; ACTIVATION; FAS; INTERLEUKIN-2; MICE; DELETION; CD95; TNF AB TCR stimulation of T lymphocytes that are activated and cycling in the presence of IL-2 leads to programmed cell death. We now show that this effect is at least partly attributable to the ability of IL-2 to dramatically increase the expression of mRNAs encoding ligands and receptors that mediate apoptosis. We also found that cyclosporin was not able,to fully inhibit the TCR induction of death molecule mRNAs or TCR-induced apoptosis, although it could completely turn off IL-2 expression. The effect of growth cytokines was further explored in T cells derived from mice bearing a homozygous deficiency of the IL-2R alpha-chain. We found that IL-2R alpha(-/-) cells were resistant to death if IL-2 was used to induce apoptosis susceptibility, but that large amounts of other T cell growth cytokines, such as IL-4 and IL-7, could induce cell cycle progression and promote TCR-induced apoptosis. However, our findings suggest that autoimmunity and lymphoproliferation in IL-2Ra(-/-) mice can result from the loss of IL-2-stimulated feedback apoptosis and that other growth cytokines are not produced at levels sufficient to compensate for this deficit. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM Lenardo@nih.gov FU NIAID NIH HHS [AI01173, AI41051] NR 40 TC 105 Z9 109 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 JAN 15 PY 1998 VL 160 IS 2 BP 763 EP 769 PG 7 WC Immunology SC Immunology GA YW267 UT WOS:000071915200030 PM 9551911 ER PT J AU Hesselgesser, J Liang, M Hoxie, J Greenberg, M Brass, LF Orsini, MJ Taub, D Horuk, R AF Hesselgesser, J Liang, M Hoxie, J Greenberg, M Brass, LF Orsini, MJ Taub, D Horuk, R TI Identification and characterization of the CXCR4 chemokine receptor in human T cell lines: Ligand binding, biological activity, and HIV-1 infectivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE CHEMOATTRACTANT; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; SIGNAL; ENTRY; SDF-1; INTERLEUKIN-8; LESTR/FUSIN; DERIVATIVES AB The CXCR4 chemokine receptor has been shown to respond to the C-X-C chemokine stromal-derived factor (SDF-1) and has recently been shown to be an important coreceptor for HIV-I infection. In the present paper we have tested a number of human T lymphocyte cell lines, including Jurkat, HUT78, GEM, and Sup-T1 far the presence of CXCR4 receptors. We found that these T cell lines bind SDF-1 alpha and SDF-1 beta with high affinity. The CXCR4 Ab 12G5 inhibited both SDF-1 binding and HIV-1(LAI)-mediated fusion of GEM. Scatchard analysis revealed the presence of approximately 150,000 SDF-1 alpha-binding sites per cell with a K-d between 5 and 10 nM. Cross-competition experiments using unlabeled SDF-1 alpha and SDF-1 beta revealed that both chemokines are equally capable of displacing their radiolabeled counterparts. Internalization studies with [125]I-SDF-1 alpha revealed that jurkat cells internalized greater than 90% of the ligand by 2 h at 37 degrees C. SDF-1 a was also chemotactic for Jurkat cells and caused an increase in the rate of extracellular acidification that was half-maximal at 18 nM SDF-1 alpha: and could be inhibited by pretreatment with the SDF-1 proteins, pertussis toxin, or the Ab 12G5. Finally, SDF-1 alpha also caused an increase in the cytosolic Ca2+ concentration in Sup-T1 cells that was abolished by preincubating the cells with pertussis toxin or PMA and inhibited by the Ab 12G5. This molecular characterization of CXCR4 receptors should prove useful in clarifying receptor interaction with SDF-1 proteins and with HIV-1: glycoprotein, with the ultimate aim of targeting the viral interaction for therapeutic intervention. C1 Berlex BioSci, Dept Immunol, Richmond, CA 94804 USA. Berlex BioSci, Dept Med Chem, Richmond, CA 94804 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Med Pathol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. RP Horuk, R (reprint author), Berlex BioSci, Dept Immunol, 15049 San Pablo Ave, Richmond, CA 94804 USA. EM Horuk@crl.com FU NHLBI NIH HHS [HL40387] NR 37 TC 123 Z9 126 U1 2 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1998 VL 160 IS 2 BP 877 EP 883 PG 7 WC Immunology SC Immunology GA YW267 UT WOS:000071915200043 PM 9551924 ER PT J AU Wang, RF Johnston, SL Southwood, S Sette, A Rosenberg, SA AF Wang, RF Johnston, SL Southwood, S Sette, A Rosenberg, SA TI Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; CLASS-I; CANCER ANTIGENS; GENE; IMMUNOTHERAPY; HLA; IDENTIFICATION; MOLECULES AB Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated Ags presented by MHC class I molecules, The infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Two T cell epitopes derived from tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be recognized by HLA-A31 restricted TIL586 and its T cell clones, In this study we tested the hypothesis that these two peptides can be recognized by CTL from non-HLA-A31 patients with melanoma, It was found that both peptides were capable of binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype, Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting that a single TCR can recognize peptide/A31 and peptide/A33 complexes, However, peptide titration experiments showed that the affinity of TCR receptor to peptide/A33 could be higher than that to the peptide/A31, These studies have important implications for the development of peptide-based cancer vaccines. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Cytel Corp, San Diego, CA 92121 USA. RP Wang, RF (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM rongfu@pop.nci.nih.gov FU PHS HHS [N01-A1-45241] NR 36 TC 88 Z9 90 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 JAN 15 PY 1998 VL 160 IS 2 BP 890 EP 897 PG 8 WC Immunology SC Immunology GA YW267 UT WOS:000071915200045 PM 9551926 ER PT J AU Guignard, F Combadiere, C Tiffany, HL Murphy, PM AF Guignard, F Combadiere, C Tiffany, HL Murphy, PM TI Gene organization and promoter function for CC chemokine receptor 5 (CCR5) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIV-1 INFECTION; MOLECULAR-CLONING; EXPRESSION; INTERLEUKIN-8; MIP-1-ALPHA; RANTES; MIP-1-BETA; CELLS; INDIVIDUALS; ENTRY AB CC chemokine receptor 5 (CCR5) functions physiologically as a receptor for the leukocyte chemoattractants macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and RANTES, and functions pathologically as a key cell entry coreceptor for HIV-1?. The factors that regulate CCR5 expression may be useful therapeutic targets for HIV-I infection. To identify nuclear regulatory factors, we have located and functionally characterized the CCR5 gene promoter. The gene consists of two exons separated by a 1.9-kb intron. Exon I contains 43 bp of the 5'-untranslated region; exon 2 contains Il bp of the 5'-untranslated region and the complete open reading frame. primer extension analysis identified two adjacent transcriptional start points (tsp) that map to the first 2 bp found in the longest known CCR5 cDNA sequence. A TATA box is present 31 bp upstream from the first tsp. CCR5 mRNA was detected constitutively in both primary human myeloid and lymphoid cells by Northern blot hybridization. Consistent with this, transcription of a chloramphenicol acetyltransferase reporter gene was constitutively activated in both transiently transfected myeloid and lymphoid cell lines by the 80-bp gene fragment located immediately upstream of the tsp. Deletion analysis located a strong silencer element between nucleotides -244 and -80, and a strong enhancer element between -486 and -244. These results suggest that the gene region between -486 and -1 may regulate the expression of CCR5 in monocyte/macrophages and T lymphocytes. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 46 TC 43 Z9 44 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 JAN 15 PY 1998 VL 160 IS 2 BP 985 EP 992 PG 8 WC Immunology SC Immunology GA YW267 UT WOS:000071915200057 PM 9551938 ER PT J AU Malinda, KM Sidhu, GS Banaudha, KK Gaddipati, JP Maheshwari, RK Goldstein, AL Kleinman, HK AF Malinda, KM Sidhu, GS Banaudha, KK Gaddipati, JP Maheshwari, RK Goldstein, AL Kleinman, HK TI Thymosin alpha(1) stimulates endothelial cell migration, angiogenesis, and wound healing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC HEPATITIS-B; IN-VIVO; BASEMENT-MEMBRANE; INTERFERON; LAMININ; MODULATION; EXPRESSION; GROWTH AB In wound healing, lymphoid cells release soluble factors that attract fibroblasts and macrophages, initiating repair, endothelial cell migration, angiogenesis, and matrix production. We analyzed the effect of thymosin a alpha(1) (T alpha(1)) On endothelial cell migration, angiogenesis, and wound healing. T alpha(1), a 28 amino acid peptide initially isolated from the thymus, enhanced the morphologic differentiation of endothelial cells and was a potent chemoattractant for endothelial cells and monocytes in vitro. In vivo, T alpha(1), stimulated angiogenesis in a subcutaneous model. When given either topically or i.p., it accelerated wound healing in a punch model, demonstrating that T alpha(1) promotes angiogenesis and wound healing. C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Ctr Combat Casualty & Life Sustainment Res, Bethesda, MD 20814 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Kleinman, HK (reprint author), NIDR, CDBRB, NIH, 30 Convent Dr,MSC 4370,Bldg 30,Room 433, Bethesda, MD 20892 USA. NR 28 TC 34 Z9 41 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1998 VL 160 IS 2 BP 1001 EP 1006 PG 6 WC Immunology SC Immunology GA YW267 UT WOS:000071915200059 PM 9551940 ER PT J AU Camaioni, E Boyer, JL Mohanram, A Harden, TK Jacobson, KA AF Camaioni, E Boyer, JL Mohanram, A Harden, TK Jacobson, KA TI Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y(1) receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MODIFIED ADENOSINE-ANALOGS; PHOSPHOLIPASE-C; P-2Y-PURINOCEPTOR AGONISTS; PURINERGIC RECEPTOR; PURINOCEPTORS; IDENTIFICATION; NUCLEOSIDES; NUCLEOTIDES AB Adenosine 3',5'- and 2',5'-bisphosphates previously were demonstrated to act as competitive antagonists at the P2Y(1) receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329). 2'- and 3'-Deoxyadenosine bisphosphate analogues containing various structural modifications at the 2- and B-positions of the adenine ring, on the ribose moiety, and on the phosphate groups have been synthesized with the goal of developing more potent and selective P2Y(1) antagonists. Single-step phosphorylation reactions of adenosine nucleoside precursors were carried out. The activity of each analogue at P2Y(1) receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-MeSATP (antagonist effect). Both 2'- and 3'-deoxy modifications were well tolerated. The N-6-methyl modification both enhanced antagonistic potency (IC50 330 nM) of 2'-deoxyadenosine 3',5'-bisphosphate by 17-fold and eliminated residual agonist properties observed with the lead compounds. The N-6-ethyl modification provided intermediate potency as an antagonist, while the N-6-propyl group completely abolished both agonist and antagonist properties. 2-Methylthio and 2-chloro analogues were partial agonists of intermediate potency. A 2'-methoxy group provided intermediate potency as an antagonist while enhancing agonist activity. An N-1-methyl analogue was a weak antagonist with no agonist activity. An 8-bromo substitution and replacement of the N-6-amino group with methylthio, chloro, or hydroxy groups greatly reduced the ability to interact with P2Y(1) receptors. Benzoylation or dimethylation of the N-6-amino group also abolished or greatly diminished the antagonist activity. In summary, our results further define the structure-activity of adenosine bisphosphates as P2Y(1) receptor antagonists and have led to the identification of the most potent antagonist reported to date for this receptor. C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, LBC, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Camaioni, Emidio/0000-0002-8529-0849 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NHLBI NIH HHS [HL54889]; NIGMS NIH HHS [GM38213] NR 26 TC 114 Z9 117 U1 0 U2 1 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 JAN 15 PY 1998 VL 41 IS 2 BP 183 EP 190 DI 10.1021/jm970433l PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YR858 UT WOS:000071538200006 PM 9457242 ER PT J AU Keverline-Frantz, KI Boja, JW Kuhar, MJ Abraham, P Burgess, JP Lewin, AH Carroll, FI AF Keverline-Frantz, KI Boja, JW Kuhar, MJ Abraham, P Burgess, JP Lewin, AH Carroll, FI TI Synthesis and ligand binding of tropane ring analogues of paroxetine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACID METHYL-ESTERS; DOPAMINE TRANSPORTER; COCAINE ANALOGS; HIGH-AFFINITY; NOREPINEPHRINE TRANSPORTERS; MOLECULAR MECHANISMS; SELECTIVE COMPOUNDS; UPTAKE INHIBITORS; SEROTONIN UPTAKE; AMPHETAMINE AB (3S,4R)-4-(4-Fluorophenyl)-3-[[3,4-(methylenedioxy)phenoxy]methyl] piperidine [(3S,9R)-3, paroxetine] is a selective serotonin reuptake inhibitor (SSRI) used as an antidepressant in humans. In previous studies, we reported that certain (1R)-3 beta-(substituted phenyl)nortropane-2 beta-carboxylic acid methyl esters (2a) exhibited high affinity and reasonable selectivity for the serotonin transporter (5-HTT). The major structural differences between 2a and (3S,4R)-3 are that 2a possesses a different absolute stereochemistry and has an ethylene bridge not present in 3. In addition, 2a possesses a carbomethoxy substituent adjacent to the aryl ring, whereas (3S,4R)-3 contains a [3,4-(methylenedioxy)phenoxy]methyl group. In this study, we present the synthesis and biological evaluations of six of the possible eight isomers of 3-(4-fluorophenyl)-2-[[3,4-(methylenedioxy)phenoxy]methyl]propane (4). The data for inhibition of [H-3]paroxetine binding show that (1R)-2 beta,3 alpha-4c, which has the same stereochemistry as paroxetine, has the highest affinity at the 5-HTT. Strikingly, the most potent compounds for inhibition of [H-3]WIN-35,428 binding were not the (1R)-2 beta,3 beta-isomers but rather (1R)-2 beta,3 alpha-4c and (1S)-2 beta,3 alpha-4f. Conformational analyses show that these isomers exist in a flattened boat conformation with pseudoequatorial substituents. Thus, the binding data show that this conformation is recognized by the DAT-associated binding site and also suggest that this conformation of paroxetine is recognized by the 5-HTT-associated binding site. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Addict Res Ctr, Neurosci Branch, Baltimore, MD 21224 USA. RP Carroll, FI (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIDA NIH HHS [DA05477] NR 43 TC 19 Z9 19 U1 0 U2 1 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 JAN 15 PY 1998 VL 41 IS 2 BP 247 EP 257 DI 10.1021/jm970669p PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YR858 UT WOS:000071538200011 PM 9457247 ER PT J AU Sawada, H Nishii, K Suzuki, T Hasegawa, K Hata, T Nagatsu, I Kreitman, RJ Pastan, I Nagatsu, T Kobayashi, K AF Sawada, H Nishii, K Suzuki, T Hasegawa, K Hata, T Nagatsu, I Kreitman, RJ Pastan, I Nagatsu, T Kobayashi, K TI Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE catecholamine metabolism; sympathetic nervous system; dopamine beta-hydroxylase; recombinant immunotoxin; cell targeting ID DOPAMINE-BETA-HYDROXYLASE; MOUSE FETAL DEVELOPMENT; INTERLEUKIN-2 RECEPTOR; PSEUDOMONAS EXOTOXIN; ORTHOSTATIC HYPOTENSION; COMPLETE REGRESSION; CHAIN IMMUNOTOXIN; GENE-EXPRESSION; HUMAN CARCINOMA; RATS AB Autonomic neuropathy in several neurodegenerative disorders results from disturbance in physiological functions of different cell types in the central anti peripheral nervous systems, For a clearer understanding of the etiology and pathogenesis of the autonomic disorders it is necessary to create animal models in which degeneration of the causative neuronal types can be induced, Immunotoxin-mediated cell targeting (IMCT) is a novel transgenic mouse technology for eliminating selective cell types with the cytotoxic activity of a recombinant immunotoxin anti-Tac(Fv)-PE40. In this study we conditionally disrupted peripheral catecholaminergic cells with IMCT to generate a mouse model developing autonomic failure based on primary defects of the sympathetic nervous system. Transgenic mice expressing human interleukin-2 receptor alpha subunit under the control of the dopamine beta-hydroxylase gene promoter were intravenously treated with a proper dose of anti-Tac(Fv)-PE40. The immunotoxin induced a selective loss of the target cells in peripheral tissues of the transgenic mice and an impairment of catecholamine metabolism in the tissues, Targeting of the peripheral catecholaminergic cells resulted in severe and progressive phenotypic abnormalities mainly characterized by cardiac dysfunction, hypoactivity, and hypothermia, which explain development of autonomic neuropathy. Our IMCT strategy is useful for elucidating the involvement of different neuronal types and their interactions in the development and symptom of autonomic disorders. (C) 1998 Wiley-Liss, Inc. C1 Nara Inst Sci & Technol, Res & Educ Ctr Genet Informat, Nara 63001, Japan. Fujita Hlth Univ, Sch Med, Div Smooth Muscle Res, Aichi, Japan. Fujita Hlth Univ, Sch Med, Inst Comprehens Med Sci, Aichi, Japan. Fujita Hlth Univ, Sch Med, Dept Anat, Aichi, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kobayashi, K (reprint author), Nara Inst Sci & Technol, Res & Educ Ctr Genet Informat, 8916-5 Takayama, Nara 63001, Japan. EM kobayasi@gtc.aist-nara.nc.jp NR 41 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN 15 PY 1998 VL 51 IS 2 BP 162 EP 173 DI 10.1002/(SICI)1097-4547(19980115)51:2<162::AID-JNR5>3.3.CO;2-G PG 12 WC Neurosciences SC Neurosciences & Neurology GA YR490 UT WOS:000071500500005 PM 9469570 ER PT J AU Berger, EA Doms, RW Fenyo, EM Korber, BTM Littman, DR Moore, JP Sattentau, QJ Schuitemaker, H Sodroski, J Weiss, RA AF Berger, EA Doms, RW Fenyo, EM Korber, BTM Littman, DR Moore, JP Sattentau, QJ Schuitemaker, H Sodroski, J Weiss, RA TI A new classification for HIV-1 SO NATURE LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; INFECTION; INDIVIDUALS; RESISTANCE; PHENOTYPE C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Karolinska Inst, Microbiol & Tumorbiol Ctr, EC Concerted Act HIV Variat, S-17177 Stockholm, Sweden. Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. NYU, Med Ctr, Howard Hughes Med Inst, New York, NY 10016 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Ctr Immunol Marseille Luminy, F-13288 Marseille, France. Netherlands Red Cross, Blood Transfus Serv, Cent Lab, Dept Clin Viroimmunol, Amsterdam, Netherlands. Univ Amsterdam, Expt & Clin Immunol Lab, Amsterdam, Netherlands. Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 236, Bethesda, MD 20892 USA. NR 10 TC 617 Z9 635 U1 3 U2 18 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 15 PY 1998 VL 391 IS 6664 BP 240 EP 240 DI 10.1038/34571 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YR328 UT WOS:000071484400033 PM 9440686 ER PT J AU Ohtaka-Maruyama, C Wang, XY Ge, H Chepelinsky, AB AF Ohtaka-Maruyama, C Wang, XY Ge, H Chepelinsky, AB TI Overlapping Sp1 and AP2 binding sites in a promoter element of the lens-specific MIP gene SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR AP-2; MAJOR INTRINSIC PROTEIN; CHICKEN DELTA-1-CRYSTALLIN GENE; A-CRYSTALLIN GENE; EXPRESSION; ACTIVATION; MOUSE; FAMILY; SEQUENCE; EMBRYOGENESIS AB The MIP gene, the founder of the MIP family of channel proteins, is specifically expressed in fiber cells of the ocular lens and expression is regulated temporally and spatially during development. We previously found that a DNA fragment containing 253 bp of 5'-flanking sequence and 42 bp of exon 1 of the human MIP gene contains regulatory elements responsible for lens-specific expression of the MIP gene, In this report we have analyzed the function of overlapping Spl and AP2 binding sites present in the MIP promoter, Using DNase I footprinting analysis we found that purified Spl and AP2 transcription factors interact with several domains of the human MIP promoter sequence -253/+42, Furthermore, addition of purified Spl to Drosophila nuclear extracts activates in vitro transcription from the MIP promoter -253/+42, This promoter activity is competed by oligonucleotides containing domains foot-printed with Spl, Using promoter-reporter gene (CAT) constructs we found that the sequence -39/-70 contains a cis regulatory element essential for promoter activity in transient assays in lens cells, EMSA analysis showed that lens nuclear extracts contain factors that bind to the MIP 5'-flanking sequence containing overlapping Spl and AP2 binding domains at positions -37/-65. Supershift experiments with lens nuclear extracts indicated that Sp3 is also able to interact with this regulatory element, suggesting that Spl and Sp3 may be involved in regulation of transcription of the MIP gene in the lens. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chepelinsky, AB (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ohtaka-Maruyama, chiaki/G-6943-2013 NR 61 TC 25 Z9 25 U1 0 U2 2 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 JAN 15 PY 1998 VL 26 IS 2 BP 407 EP 414 DI 10.1093/nar/26.2.407 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV005 UT WOS:000071779000003 PM 9421492 ER PT J AU Lavrik, OI Nasheuer, HP Weisshart, K Wold, MS Prasad, R Beard, WA Wilson, SH Favre, A AF Lavrik, OI Nasheuer, HP Weisshart, K Wold, MS Prasad, R Beard, WA Wilson, SH Favre, A TI Subunits of human replication protein A are crosslinked by photoreactive primers synthesized by DNA polymerases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; SIMIAN VIRUS-40 DNA; HIV-1 REVERSE-TRANSCRIPTASE; ALPHA-PRIMASE; FUNCTIONAL-CHARACTERIZATION; BINDING-PROTEIN; MULTIPLE STAGES; SV40 ORIGIN; IN-VITRO; FACTOR-A AB Human replication protein A (huRPA) is a multisubunit protein which is involved in DNA replication, repair and recombination processes, It exists as a stable heterotrimer consisting of p70, p32 and p14 subunits, To understand the contribution of huRPA subunits to DNA binding we applied the photoaffinity labeling technique, The photoreactive oligonucleotide was synthesized in situ by DNA polymerases, 5-[N-(2-nitro-5-azidobenzoyl)-trans-3-aminopropenyl-1]deoxyuridine-5'-triphosphate (NABdUTP) was used as substrate for elongation of a radiolabeled primer template either by human DNA polymerase alpha primase (pol alpha), human DNA polymerase beta (pol beta) or Klenow fragment of Escherichia coli DNA polymerase I (KF). The polymerase was incubated with NABdUTP and radiolabeled primer-template in the presence or absence of huRPA, The reaction mixtures were then irradiated with monochromatic UV light (315 nm) and the crosslinked products were separated by SDS-PAGE. The results clearly demonstrate crosslinking of the huRPA p70 and p32 subunits with DNA, The p70 subunit appears to bind to the single-stranded part of the DNA duplex, the p32 subunit locates near the 3'-end of the primer, while the p14 subunit locates relatively far from the 3'-end of the primer. This approach opens new possibilities for analysis of huRPA loading on DNA in the course of DNA replication and DNA repair. C1 Inst Jacques Monod, CNRS, F-75251 Paris 05, France. Russian Acad Sci, Inst Bioorgan Chem, Novosibirsk 630090, Russia. Inst Mol Biotechnol Jena, D-07708 Jena, Germany. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Lavrik, OI (reprint author), Inst Jacques Monod, CNRS, 2 Pl Jussieu, F-75251 Paris 05, France. RI Nasheuer, Heinz/B-9025-2008; Wold, Marc/F-5806-2010; Lavrik, Olga /G-4641-2013 NR 46 TC 51 Z9 54 U1 0 U2 0 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 JAN 15 PY 1998 VL 26 IS 2 BP 602 EP 607 DI 10.1093/nar/26.2.602 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV005 UT WOS:000071779000033 PM 9421522 ER PT J AU Anson, RM Croteau, DL Stierum, RH Filburn, C Parsell, R Bohr, VA AF Anson, RM Croteau, DL Stierum, RH Filburn, C Parsell, R Bohr, VA TI Homogenous repair of singlet oxygen-induced DNA damage in differentially transcribed regions and strands of human mitochondrial DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HAMSTER OVARY CELLS; OXIDATIVE DAMAGE; MAMMALIAN MITOCHONDRIA; SUBSTRATE-SPECIFICITY; RINR-38 CELLS; GLYCOSYLASE; SITES; RAT; NUCLEAR; 8-OXOGUANINE AB Photoactivated methylene blue was used to damage purified DNA and the mitochondrial DNA (mtDNA) of human fibroblasts in culture. The primary product of this reaction is the DNA lesion 7-hydro-8-oxo-deoxyguanosine (8-oxo-dG). The DNA damage was quantitated using Escherichia coli formamido-pyrimidine DNA glycosylase (Fpg) in a gene-specific damage and repair assay, Assay conditions were refined to give incision at ail enzyme-sensitive sites with minimal non-specific cutting, Cultured fibroblasts were exposed to photoactivated methylene blue under conditions that would produce an average of three oxidative lesions per double-stranded mitochondrial genome. Within 9 h, 47% of this damage had been removed by the cells, This removal was due to repair rather than to replication, cell loss or degradation sf damaged genomes, The rate of repair was measured in both DNA strands of the frequently transcribed ribosomal region of the mitochondrial genome and in both strands of the non-ribosomal region, Fpg-sensitive alkali-resistant oxidative base damage was efficiently removed from human mtDNA with no differences in the rate of repair between strands or between two different regions of the genome that differ substantially with regard to transcriptional activity. C1 NIA, Genet Mol Lab, Baltimore, MD 21224 USA. NIA, Biol Chem Lab, Baltimore, MD 21224 USA. Johns Hopkins Hosp, Dept Biol, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Dept Pharmacol & Mol Sci, Baltimore, MD 21287 USA. RP Bohr, VA (reprint author), NIA, Genet Mol Lab, Baltimore, MD 21224 USA. NR 42 TC 62 Z9 64 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 JAN 15 PY 1998 VL 26 IS 2 BP 662 EP 668 DI 10.1093/nar/26.2.662 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV005 UT WOS:000071779000042 PM 9421531 ER PT J AU Craig, C Kim, M Ohri, E Wersto, R Katayose, D Li, ZW Choi, YH Mudahar, B Srivastava, S Seth, P Cowan, K AF Craig, C Kim, M Ohri, E Wersto, R Katayose, D Li, ZW Choi, YH Mudahar, B Srivastava, S Seth, P Cowan, K TI Effects of adenovirus-mediated p16(INK4A) expression on cell cycle arrest are determined by endogenous p16 and Rb status in human cancer cells SO ONCOGENE LA English DT Article DE adenovirus; gene therapy; breast cancer; p16; cyclin dependent kinase inhibitors ID DEPENDENT KINASE INHIBITOR; RETINOBLASTOMA SUSCEPTIBILITY GENE; TUMOR-SUPPRESSOR GENE; CDK INHIBITORS; POTENTIAL MEDIATOR; GROWTH SUPPRESSION; PRODUCT PRB; PROTEIN; P21; PHOSPHORYLATION AB We constructed an adenoviral vector containing human p16 cDNA in order to evaluate the cytotoxic effects of exogenous p16 expression on cancer cell proliferation and to explore the potential use of p16 in cancer gene therapy, Following infection of human breast (MCF-7, MDA-MB-231, and BT549), osteosarcoma (U-2 OS and Saos-2), cervical (C33a), and lung cancer (H358) cell lines with the recombinant adenovirus Adp16, high levels of p16 expression were observed in all cell lines. Cancer cell lines which were mutant or null for p16 but wild-type for the retinoblastoma gene product (pRb) (MCF-7, MDA-MB-231, BT549 and U-2 OS) were 7-22-fold more sensitive to the cytotoxic effects of Adp16 than to a control virus, In contrast, cancer cell lines which were wild-type for p16 but mutant or null for pRb (Saos-2, C33a and H358) were 3.0.CO;2-R PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YP872 UT WOS:000071324500020 PM 9450890 ER PT J AU Hampel, H Sunderland, T Kotter, HU Schneider, C Teipel, SJ Padberg, F Dukoff, R Levy, J Moller, HJ AF Hampel, H Sunderland, T Kotter, HU Schneider, C Teipel, SJ Padberg, F Dukoff, R Levy, J Moller, HJ TI Decreased soluble interleukin-6 receptor in cerebrospinal fluid of patients with Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; cerebrospinal fluid; interleukin-6; soluble interleukin-6 receptor; family history; ELISA ID GROWTH-FACTORS; IL-6; CELLS; EXPRESSION; ASTROCYTES; CYTOKINES; CULTURES AB The function of the cytokine interleukin-6 (IL-6) is augmented by soluble IL-6 receptors (sIL-6R). We investigated cerebrospinal fluid sIL-6R concentrations in patients with Alzheimer's disease (AD) compared to age-matched healthy subjects and individuals with at least one first degree relative with AD. We found a statistically significant decrease in sIL-6R levels in the AD group compared to controls. Complete analysis of the IL-6R complex seems crucial to better understand the impact of IL-6 in AD pathophysiology. (C) 1998 Elsevier Science B.V. C1 Univ Munich, Sch Med, Dept Psychiat, Geriatr Psychiat Branch, D-80336 Munich, Germany. NIMH, NIH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Hampel, H (reprint author), Univ Munich, Sch Med, Dept Psychiat, Geriatr Psychiat Branch, Nussbaumstr 7, D-80336 Munich, Germany. EM ham-pel@psy.med.uni.muenchen.de NR 23 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 12 PY 1998 VL 780 IS 2 BP 356 EP 359 DI 10.1016/S0006-8993(97)01355-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YZ503 UT WOS:000072260600021 PM 9507194 ER PT J AU Harris, BD Moody, EJ Skolnick, P AF Harris, BD Moody, EJ Skolnick, P TI Stereoselective actions of halothane at GABA(A) receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE anesthetic, inhalational; GABA(A) receptor complex; halothane; stereoselectivity; flunitrazepam; GABA (gamma-aminobutyric acid) ID VOLATILE ANESTHETICS; OPTICAL ISOMERS; ISOFLURANE; BINDING; STEREOSPECIFICITY; STEREOISOMERS; INHIBITION; ENFLURANE; CHANNELS; COMPLEX AB Isoflurane anesthesia exhibits stereoselectivity, and a corresponding stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) receptors in vitro. The objective of the present study was to determine if the positive modulatory actions of halothane at GABA(A) receptors exhibited a similar stereoselectivity. Both (R)- and (S)-halothane ((+)- nd (-)- isomers, respectively) enhanced [H-3]flunitrazepam binding to brain membranes in a concentration dependent manner without a significant difference in either potency (EC50) or efficacy (E-max). While both (R)- and (S)-halothane enhanced [H-3]muscimol binding, the potency of the (+)-isomer was slightly greater than the corresponding(-)-isomer (0.91 +/- 0.17 versus 1.45 +/- 0.04% atmospheres, respectively(P < 0.02)). Thus, subtle structural differences between inhalational anesthetics can have a significant impact on the degree of stereoselectivity at the receptor level and may provide insights for the development of more specific drugs. (C) 1998 Published by Elsevier Science B.V. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Crit Care Med, Washington, DC 20010 USA. Johns Hopkins Hosp, Div Cardiac, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. Eli Lilly & Co, Lilly Res Lab, Neurosci Discovery, Indianapolis, IN 46285 USA. RP Harris, BD (reprint author), NIDDK, Neurosci Lab, NIH, Bldg 8A,Room 115, Bethesda, MD 20892 USA. NR 18 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 12 PY 1998 VL 341 IS 2-3 BP 349 EP 352 DI 10.1016/S0014-2999(97)01488-X PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA323 UT WOS:000072352000032 PM 9543259 ER PT J AU Heimbecher, S Lee, YC Tabibi, SE Yalkowsky, SH AF Heimbecher, S Lee, YC Tabibi, SE Yalkowsky, SH TI Mechanism of dansylation of the polyamine pentaazapentacosane center dot 5 HCl SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE pentaazapentacosane pentahydrochloride; polyamines; dansylation; dansyl chloride AB Dansylation of the pentaamine pentaazapentacosane .5 HCl (PAPC) produces only the perdansyl product. This occurs even under conditions of pH and dansyl chloride concentration most likely to produce partially dansylated products. This result is explained by a mechanism whereby only completely unionized amine molecules will dansylate. The proposed mechanism is supported by the dansylation versus pH profile of PAPC versus that of a reference monoamine (piperidine . HCl). After 4 h at room temperature and pH 9.5, 100% of piperidine is dansylated while under the same conditions only 10% of PAPC is derivatized. A pH greater than 10.5 is required to completely dansylate PAPC. This difference is significantly greater than would be predicted from the pK(a) values but it is consistent with the proposed mechanism. (C) 1998 Elsevier Science B.V. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, NIH, Pharmaceut Resources Branch, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JAN 12 PY 1998 VL 160 IS 1 BP 21 EP 29 DI 10.1016/S0378-5173(97)00315-3 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YW786 UT WOS:000071973900003 ER PT J AU Cole, NB Ellenberg, J Song, J DiEuliis, D Lippincott-Schwartz, J AF Cole, NB Ellenberg, J Song, J DiEuliis, D Lippincott-Schwartz, J TI Retrograde transport of Golgi-localized proteins to the ER SO JOURNAL OF CELL BIOLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; INTERMEDIATE COMPARTMENT PROTEIN; ATP-COUPLED TRANSPORT; CHAIN BINDING-PROTEIN; HUMAN KDEL RECEPTOR; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; MEMBRANE-PROTEIN; BREFELDIN-A; MOLECULAR-CLONING AB The ER is uniquely enriched in chaperones and folding enzymes that facilitate folding and unfolding reactions and ensure that only correctly folded and assembled proteins leave this compartment. Here we address the extent to which proteins that leave the ER and localize to distal sites in the secretory pathway are able to return to the ER folding environment during their lifetime, Retrieval of proteins back to the ER was studied using an assay based on the capacity of the ER to retain misfolded proteins. The lumenal domain of the temperature-sensitive viral glycoprotein VSVGtsO45 was fused to Golgi or plasma membrane targeting domains. At the nonpermissive temperature, newly synthesized fusion proteins misfolded and were retained in the ER, indicating the VSVGtsO45 ectodomain was sufficient for their retention within the ER. At the permissive temperature, the fusion proteins were correctly delivered to the Golgi complex or plasma membrane, indicating the lumenal epitope of VSVGtsO45 also did not interfere with proper targeting of these molecules, Strikingly, Golgi-localized fusion proteins, but not VSVGtsO45 itself, were found to redistribute back to the ER upon a shift to the nonpermissive temperature, where they misfolded and were retained. This occurred over a time period of 15 min-2 h depending on the chimera, and did not require new protein synthesis. Significantly, recycling did not appear to be induced by misfolding of the chimeras within the Golgi complex. This suggested these proteins normally cycle between the Golgi and ER, and while passing through the ER at 40 degrees C become misfolded and retained. The attachment of the thermosensitive VSVGtsO45 lumenal domain to proteins promises to be a useful tool for studying the molecular mechanisms and specificity of retrograde traffic to the ER. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 76 TC 133 Z9 135 U1 0 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 JAN 12 PY 1998 VL 140 IS 1 BP 1 EP 15 DI 10.1083/jcb.140.1.1 PG 15 WC Cell Biology SC Cell Biology GA YR491 UT WOS:000071500600001 PM 9425149 ER PT J AU Kwon, TK Buchholz, MA Jun, DY Kim, YH Nordin, AA AF Kwon, TK Buchholz, MA Jun, DY Kim, YH Nordin, AA TI The differential catalytic activity of alternatively spliced cdk2 alpha and cdk2 beta in the G(1)/S transition and early S phase SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; RETINOBLASTOMA PROTEIN; MAMMALIAN-CELLS; CDK2; INHIBITORS; BINDING; ROLES AB Progression through the G(1)/S transition of the cell cycle is regulated by cyclin E/cdk2 and cyclin A/cdk2 complexes, We demonstrate that there are two forms of murine cdk2, (cdk2 alpha and beta), Cdk2 alpha consist of 298 amino acids, while cdk2 beta contains a 48-amino-acid insert between Met (196) and Val (197) of cdk2 alpha, Cdk2 beta results from differential splicing of the primary RNA transcript of the cdk2 gene. Although human cdk2 genomic DNA contained the sequence of the insert for the beta form, cdk2 beta was not detected by either Western blot or RT-PCR in human T-cells or several other human cell lines, Cdk2 beta expression in murine cells was similar to that of the phosphorylated, catalytically active form of cdk2 alpha. Cdk2 alpha and cdk2 beta have very similar binding activity to cyclin E and to the cdk inhibitor p27(KipI), The alternatively spliced cdk2 beta possesses catalytic activity in vivo and in vitro, The differential catalytic activity of these two forms of cdk2, suggests that cdk2 alpha and cdk2 beta may perform different functions at or near the G(1)/S transition and early S phase. (C) 1998 Academic Press. C1 NIA, Gerontol Res Ctr, Immunol Lab, NIH, Baltimore, MD 21224 USA. Kyungpook Natl Univ, Coll Nat Sci, Dept Microbiol, Taegu 702701, South Korea. RP Nordin, AA (reprint author), NIA, Gerontol Res Ctr, Immunol Lab, NIH, 4940 Eastern Ave,Box 21, Baltimore, MD 21224 USA. NR 21 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1998 VL 238 IS 1 BP 128 EP 135 DI 10.1006/excr.1997.3816 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YV190 UT WOS:000071798400015 PM 9457065 ER PT J AU Danen, EHJ Marcinkiewicz, C Cornelissen, IMHA van Kraats, AA Pachter, JA Ruiter, DJ Niewiarowski, S van Muijen, GNP AF Danen, EHJ Marcinkiewicz, C Cornelissen, IMHA van Kraats, AA Pachter, JA Ruiter, DJ Niewiarowski, S van Muijen, GNP TI The disintegrin eristostatin interferes with integrin alpha 4 beta 1 function and with experimental metastasis of human melanoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID INDUCED BINDING-SITE; FIBRONECTIN-RECEPTOR; VITRONECTIN-RECEPTOR; TUMOR PROGRESSION; NUDE-MICE; ALPHA-V-BETA-3 INTEGRINS; MONOCLONAL-ANTIBODY; MALIGNANT-MELANOMA; ENDOTHELIAL-CELLS; RGD LOOP AB Peptides containing the integrin recognition sequence, RGD, call inhibit experimental metastasis of mouse melanoma cells, but the. integrin(s) affected in these experiments is unknown, Besides "classical" RGD-binding integrins such as alpha 5 beta 1 and alpha v beta 3, RGD has been reported to bind alpha 4 beta 1, and mAbs to alpha 4 beta 1 can inhibit melanoma metastasis, We investigated the mode of action of the disintegrin eristostatin, an RGD-containing peptide isolated from snake venom, in a human melanoma experimental metastasis model, Lung colonization following i.v. injection of MV3 cells in nude mice was strongly inhibited by eristostatin. MV3 cells bound FITC-eristostatin and adhered to aristostatin-coated wells, This adhesion was partially inhibited by a GRGDSP peptide and by alpha 4 mAb. finding of FITC-eristostatin to Jurkat cells and adhesion of Jurkat (but not K562) cells to eristostatin-coated wells further suggested that eristostatin binds alpha 4 beta 1, even though, again, alpha 4 mAb only partially inhibited adhesion, Expression of alpha 4 beta 1 was enhanced in metastatic melanoma cells compared to normal melanocytes and nonmetastatic melanoma cells, Finally, eristostatin inhibited adhesion of both MV3 and CHO alpha 4 cells to the alpha 4 beta 1-ligand VCAM-1, while adhesion to other ligands via other integrins was not affected, These findings demonstrate that inhibition of melanoma cell metastasis by RGD-containing peptides such as eristostatin, may be due to interference with alpha 4 beta 1-VCAM binding, in addition to inhibition of the classical RGD-binding integrins. (C) 1998 Academic Press. C1 Univ Nijmegen Hosp, Dept Pathol, Nijmegen, Netherlands. Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19122 USA. Temple Univ, Sch Med, Sol Sherry Thrombosis Ctr, Philadelphia, PA 19122 USA. Schering Plough Corp, Res Inst, Dept Tumor Biol, Kenilworth, NJ 07033 USA. RP Danen, EHJ (reprint author), NIDR, CDBRB, NIH, Bldg 30,Room 408, Bethesda, MD 20892 USA. EM edanen@yoda.nidr.nih.gov FU NHLBI NIH HHS [HL45486]; NIDCR NIH HHS [DE 11844] NR 69 TC 45 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1998 VL 238 IS 1 BP 188 EP 196 DI 10.1006/excr.1997.3821 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YV190 UT WOS:000071798400021 PM 9457071 ER PT J AU Gray, RH Wawer, MJ Serwadda, D Sewankambo, N Li, CJ Wabwire-Mangen, F Paxton, L Kiwanuka, N Kigozi, G Konde-Lule, J Quinn, TC Gaydos, CA McNairn, D AF Gray, RH Wawer, MJ Serwadda, D Sewankambo, N Li, CJ Wabwire-Mangen, F Paxton, L Kiwanuka, N Kigozi, G Konde-Lule, J Quinn, TC Gaydos, CA McNairn, D TI Population-based study of fertility in women with HIV-1 infection in Uganda SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIGASE CHAIN-REACTION; PREGNANCY; MORTALITY; DISTRICT; DISEASE; COHORT; IMPACT; RATES; URINE AB Background To assess the effects of HIV-1 and other sexually transmitted infections on pregnancy, we undertook cross-sectional and prospective-studies of a rural population in Rakai district, Uganda. Methods 4813 sexually active women aged 15-49 years were surveyed to find out the prevalence of pregnancy by interview and selective urinary human chorionic gonadotropin tests. The incidence of recognised conception and frequency of pregnancy loss were assessed by follow-up. Samples were taken to test for HIV-1 infection, syphilis, and other sexually transmitted diseases. Findings At time of survey, 757 (21.4%) of 3544 women without HIV-1 infection or syphilis were pregnant, compared with 46 (14.6%) of 316 HIV-1-negative women with active syphilis, 117 (14.2%) of 823 HIV-1-positive women with no concurrent syphilis, and 11 (8.5%) of 130 women with both syphilis and HIV-1 infection. The multivariate adjusted odds ratio of pregnancy in HIV-1-infected women was 0.45 (95% CI 0.35-0.57); the odds of pregnancy were low both in HIV-1-infected women without symptoms (0.49 [0.39-0.62]) and in women with symptoms of HIV-1-associated disease (0.23 [0.11-0.48]). In women with concurrent HIV-1 infection and syphilis the odds ratio was 0.28 (0.14-0.55). The incidence rate of recognised pregnancy during the prospective followup study was lower in HIV-1-positive than in HIV-1-negative women (23.5 vs 30.1 per 100 woman-years; adjusted risk ratio 0.73 [0.57-0.93]). Rates of pregnancy loss were higher among HIV-1-infected than uninfected women (18.5 vs 12.2%; odds ratio 1.50 [1.01-2.27]). The prevalence of HIV-1 infection was significantly lower in pregnant than in non-pregnant women (13.9 vs 21.3%). Interpretation Pregnancy prevalence is greatly reduced in HIV-1-infected women, owing to lower rates of conception and increased rates of pregnancy loss. HIV-1 surveillance confined to pregnant women underestimates the magnitude of the HIV-1 epidemic in the general population. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat Dynam, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Columbia Univ, Sch Publ Hlth, Ctr Populat & Family Hlth, New York, NY USA. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Makerere Univ, Dept Med, Kampala, Uganda. Rakai Project, Entebbe, Uganda. NIAID, Bethesda, MD 20892 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat Dynam, Room 4030,615 N Wolfe St, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X FU NIAID NIH HHS [R01 AI34826-03]; NICHD NIH HHS [5P30HD06268] NR 33 TC 195 Z9 197 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 10 PY 1998 VL 351 IS 9096 BP 98 EP 103 DI 10.1016/S0140-6736(97)09381-1 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YT341 UT WOS:000071591900011 PM 9439494 ER PT J AU Lau, J Ioannidis, JPA Schmid, CH AF Lau, J Ioannidis, JPA Schmid, CH TI Summing up evidence: one answer is not always enough SO LANCET LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; INTRAVENOUS-MAGNESIUM; METAANALYSIS; RISK; HETEROGENEITY; QUALITY; EXAMPLE; BENEFIT AB Are meta-analyses the brave new world, or are the critics of such combined analyses right to say that the biases inherent in clinical trials make them uncombinable? Negative trials are often unreported, and hence can be missed by meta-analysts. And how much heterogeneity between trials is acceptable? A recent major criticism is that large randomised trials do not always agree with a prior meta-analysis. Neither individual trials nor meta-analyses, reporting as they do on population effects, tell how to treat the individual patient. Here we take a more rounded approach to meta-analyses, arguing that their strengths outweigh their weaknesses, although the latter must not be brushed aside. C1 Tufts Univ, New England Med Ctr Hosp, Sch Med, Div Clin Care Res, Boston, MA 02111 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Lau, J (reprint author), Tufts Univ, New England Med Ctr Hosp, Sch Med, Div Clin Care Res, Box 63,750 Washington St, Boston, MA 02111 USA. EM joseph.lau@es.nemc.org RI Ioannidis, John/G-9836-2011; OI Schmid, Christopher/0000-0002-0855-5313 NR 49 TC 410 Z9 424 U1 0 U2 9 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 10 PY 1998 VL 351 IS 9096 BP 123 EP 127 DI 10.1016/S0140-6736(97)08468-7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YT341 UT WOS:000071591900043 PM 9439507 ER PT J AU Zhang, WG Sloan-Lancaster, J Kitchen, J Trible, RP Samelson, LE AF Zhang, WG Sloan-Lancaster, J Kitchen, J Trible, RP Samelson, LE TI LAT: The ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation SO CELL LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; ADAPTER PROTEIN; SH2 DOMAINS; GRB2; PHOSPHORYLATION; SLP-76; PHOSPHOPROTEIN; ASSOCIATION AB Despite extensive study, several of the major components involved in T cell receptor-mediated signaling remain unidentified. Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma 1, and the p85 subunit of phosphoinositide 3-kinase. Deduced amino acid sequence identifies a novel integral membrane protein containing multiple potential tyrosine phosphorylation sites. We show that this protein is phosphorylated by ZAP-70/Syk protein tyrosine kinases leading to recruitment of multiple signaling molecules. Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells. C1 NICHHD, Sect Lymphocyte Signalling, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, WG (reprint author), NICHHD, Sect Lymphocyte Signalling, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 33 TC 915 Z9 938 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 9 PY 1998 VL 92 IS 1 BP 83 EP 92 DI 10.1016/S0092-8674(00)80901-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR227 UT WOS:000071473700010 PM 9489702 ER PT J AU Camp, BW Broman, SH Nichols, PL Leff, M AF Camp, BW Broman, SH Nichols, PL Leff, M TI Maternal and neonatal risk factors for mental retardation: defining the 'at-risk' child SO EARLY HUMAN DEVELOPMENT LA English DT Article DE "at risk"; prediction; neo-natal conditions ID BIRTH-WEIGHT INFANTS; SCHOOL PERFORMANCE; CEREBRAL-PALSY; INTELLIGENCE; ASSOCIATION; SURVIVAL AB Objective: To determine how mental retardation at age seven is related to certain maternal, perinatal, and neonatal characteristics. Method: A sample of 35704 children followed from the prenatal period to age 7 years in the Collaborative Perinatal Project provided data on nine maternal and pregnancy characteristics and 12 neonatal factors. Results: Low socioeconomic status of the family (SES) accounted for 44-50% of mental retardation and a low level of maternal education accounted for 20%. Other prenatal factors with significantly elevated relative risks, (P < 0.05) were maternal IQ score less than 70, weight gain in pregnancy less than 10 pounds and multiple birth. Maternal anemia in pregnancy accounted for 14% of mental retardation in blacks, and, urinary tract infections accounted for 6% of mental retardation in whites. Significant elevations in relative risk were found for major genetic and post-infection syndromes, CNS malformations, cerebral palsy, seizures, abnormal movements or tone, and low birth weight. Relative risk was also significantly increased with low 1 minute APGAR, primary apnea, and head circumference and length more than 2 SD below average but only in the low SES black subgroup, Conclusion: Early developmental events can be ranked on the basis of the strength of their association with mental retardation and such rankings can be used as a guide for defining risk status in early infancy. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Colorado, Hlth Sci Ctr, Dept Pediat, Sch Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80262 USA. NINDS, Bethesda, MD 20892 USA. Colorado State Dept Hlth, Denver, CO USA. RP Camp, BW (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pediat, Sch Med, Campus Box C-224,4200 E 9th Ave, Denver, CO 80262 USA. NR 54 TC 38 Z9 38 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JAN 9 PY 1998 VL 50 IS 2 BP 159 EP 173 DI 10.1016/S0378-3732(97)00034-9 PG 15 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA YU346 UT WOS:000071707900003 PM 9483389 ER PT J AU Malloy, MH Berendes, H AF Malloy, MH Berendes, H TI Does breast-feeding influence intelligence quotients at 9 and 10 years of age? SO EARLY HUMAN DEVELOPMENT LA English DT Article DE breast-feeding; intelligence; IQ; soy formulas ID COGNITIVE-DEVELOPMENT; CHILD-DEVELOPMENT; ATOPIC DISEASE; FORMULA; LIFE; MILK AB The effect of breast-feeding on intellectual development remains controversial. We explored this relationship in a high socioeconomic population in which breast feeding was supplemented with soy containing formulas at some time during the first year of life. As part of the 1988 National Institute of Child Health and Human Development school-based survey of two metropolitan Washington, D.C. counties to identify children in the 1978 to 1979 birth cohort who had been exposed to the chloride deficient formulas Neo-Mull-Soy and Cho-Free during infancy, information on breast-feeding was also obtained on children exposed to the chloride-deficient formulas and a group of control children exposed to other soy formulas. Because no differences in intellectual development were observed between the two groups, they were combined and the effect of breast-feeding on intellectual development at 9 and 10 years was assessed. There were 176 infants that received no breast-feeding and 342 who were breast-fed. The median duration of breast feeding was 124 days (interquartile range, 42-248 days). There were no differences in birth weight, gender or race between the infants who were breast-fed and those who were not. The mean Weschler Intelligence Scale-Revised Full Scale IQ was 122 among those breast-fed compared to 118 among those that were not (P = 0.0008). However, following adjustment by Linear regression for maternal education, paternal education and annual income the adjusted mean full scale IQ was 111 among the breast-fed and 110 among the non-breast-fed (P = 0.23). Further analyses limited to those exclusively breast-fed for the first 60 days failed to demonstrate any significant relationship between breast-feeding and IQ. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHHD, Bethesda, MD 20892 USA. RP Malloy, MH (reprint author), Univ Texas, Med Branch, Galveston, TX 77550 USA. NR 21 TC 36 Z9 38 U1 1 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JAN 9 PY 1998 VL 50 IS 2 BP 209 EP 217 DI 10.1016/S0378-3732(97)00044-1 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA YU346 UT WOS:000071707900007 PM 9483393 ER PT J AU Vaughan, M AF Vaughan, M TI Signaling by heterotrimeric G proteins minireview series SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Editorial Material ID BETA-ADRENERGIC-RECEPTOR; ADENYLATE-CYCLASE; ACTIVATION; CELL C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 15 TC 17 Z9 17 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 JAN 9 PY 1998 VL 273 IS 2 BP 667 EP 668 DI 10.1074/jbc.273.2.667 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400001 PM 9422712 ER PT J AU Biade, S Sobol, RW Wilson, SH Matsumoto, Y AF Biade, S Sobol, RW Wilson, SH Matsumoto, Y TI Impairment of proliferating cell nuclear antigen-dependent apurinic/apyrimidinic site repair on linear DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; POLYMERASE-BETA; V(D)J RECOMBINATION; ESCHERICHIA-COLI; PCNA; COMPLEMENTATION; REQUIREMENT; RESIDUES; INVITRO; PROTEIN AB Repair of apurinic/apyrimidinic (AP) sites by mammalian cell extracts was compared using circular and linear DNA substrates. Extracts prepared from DNA polymerase beta (pol beta)-proficient mouse fibroblasts repaired AP sites on both circular and linear DNA. However, extracts from the isogenic pol beta-knockout cells repaired AP sites on circular DNA but not efficiently on linear DNA. The circularity-dependent repair by the pol beta-knockout cell extract was completely inhibited by antiproliferating cell nuclear antigen (PCNA) antibody but fully restored by addition of purified PCNA. Pretreatment of the linear DNA with AP endonuclease did not improve repair, indicating that impairment of AP site repair on linear DNA by pol beta-knockout cell extracts is not due to inefficiency of damage incision but rather to deficiency at the subsequent steps. These results indicate that AP sites can be repaired on circular DNA by the PCNA-dependent pathway in addition to the pol beta-dependent pathway and that the PCNA-dependent repair mechanism is poorly functional on linear DNA in vitro. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Matsumoto, Y (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU NCI NIH HHS [CA63154, CA 06927] NR 27 TC 161 Z9 162 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 JAN 9 PY 1998 VL 273 IS 2 BP 898 EP 902 DI 10.1074/jbc.273.2.898 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400036 PM 9422747 ER PT J AU Al-Shami, A Mahanna, W Naccache, PH AF Al-Shami, A Mahanna, W Naccache, PH TI Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils - Selective activation of Jak2, Stat3, and Stat5B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR GM-CSF; PROTEIN-TYROSINE KINASE; PHOSPHATIDIC-ACID; PHOSPHOLIPASE-D; BETA(C) CHAIN; DNA-BINDING; RECEPTOR; PHOSPHORYLATION; INTERLEUKIN-3; INVOLVEMENT AB Granulocyte-macrophage colony stimulating factor (GM-CSF) regulates many of the biological functions of human neutrophils, This includes the stimulation of protein synthesis and the tyrosine phosphorylation of various proteins among which is JAK2. The present study was aimed at characterizing in detail the pattern of activation by GM-CSF of the JAK/STAT pathway in human neutrophils. The results obtained show that the stimulation of human neutrophils by GM-CSF specifically led to tyrosine phosphorylation of JAK2 and had no effect on JAK1, JAK3, or TYK2, Furthermore, GM-CSF induced the tyrosine phosphorylation of STAT3 and STAT5 but not of STAT1, STAT2, STAT4, or STAT6. Tyrosine phosphorylation of STAT3 was transient reaching its maximum at 15 min. STAT5 presented a different pattern of tyrosine phosphorylation. The anti-STAT5 antibodies identified two proteins at 94 and 92 kDa. The 94-kDa STAT5 was constitutively tyrosine phosphorylated and showed no change upon GM-CSF stimulation. On the other hand, the 92-kDa STAT5 was tyrosine phosphorylated within 1 min of GM-CSF treatment and this was maintained for at least 30 min. By the use of specific antibodies, it was determined that only STAT5B, and not STAT5A, was tyrosine phosphorylated in GM-CSF-treated neutrophils. Furthermore, GM-CSF treatment induced an increase in the ability of STAT3 and STAT5B, but not STAT5A, to bind DNA probes. The specificity of the pattern of activation of the JAK/STAT pathway suggests that it may be directly linked to the modulation of the functions of mature nondividing, human neutrophils by GM-CSF. C1 CHUL, Ctr Rech, Ctr Rech Rhumatol & Immunol, St Foy, PQ G1V 4G2, Canada. Univ Laval, Fac Med, Dept Med, St Foy, PQ G1V 4G2, Canada. NIAID, Immunogenet Lab, NIH, Bethesda, MD 20852 USA. RP Naccache, PH (reprint author), CHUL, Ctr Rech, Ctr Rech Rhumatol & Immunol, 2705 Blvd Laurier, St Foy, PQ G1V 4G2, Canada. EM paul.naccache@crchul.ulaval.ca RI Al-Shami, Amin/D-3889-2009 NR 42 TC 88 Z9 88 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 JAN 9 PY 1998 VL 273 IS 2 BP 1058 EP 1063 DI 10.1074/jbc.273.2.1058 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400058 PM 9422769 ER PT J AU Bai, G Norton, DD Prenger, MS Kusiak, JW AF Bai, G Norton, DD Prenger, MS Kusiak, JW TI Single-stranded DNA-binding proteins and neuron-restrictive silencer factor participate in cell-specific transcriptional control of the NMDAR1 gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SUBUNIT GENE; RECEPTOR; PROMOTER; IDENTIFICATION; EXPRESSION; ELEMENT; REGION; CLONING; REPRESSOR AB Our previous studies revealed that a proximal region of the N-methyl-D-aspartate receptor I (NMDAR1) promoter is important for cell-type-specific expression. We have now explored the contributions of several regulatory elements to this specificity, Deletion of the neuron restrictive silencer element partially relieved the suppression of promoter activity in C6 glioma and HeLa cells. An overlapping G(C/G)G/tandem Sp1-containing region crucial for both basal and nerve growth factor (NGF)-regulated promoter activity specifically bound nuclear proteins on its purine-rich sense strand. A faster migrating complex, single-stranded binding protein complex 1 (SBPC1), was highly enriched in HeLa cells, whereas a slower migrating complex, SBPC2, was enriched in PC12 cells. A high ratio of 2/1 complex correlated with a high level of promoter activity. NGF treatment of PC12 cells reduced SBPC1 but increased SBPC2. Competition experiments showed that the SBPC1 binding required a dG(4) sequence and the SBPC2 needed a core of TG(3)A plus a 5'-flanking sequence. Single-stranded DNA encompassing TG(3)A and/or dG(4) specifically suppressed cotransfected NMDAR1 promoter activity. UV cross-linking studies indicated that a 31.5-kDa protein mainly formed SBPC1, whereas SBPC1 contained several larger proteins, Our results suggest that neuron-restrictive silencer factor and single-stranded DNA-binding proteins may both play a role in cell-type specificity of the NMDAR1 gene, and the latter may also be involved in basal and NGF-regulated activity. C1 NIA, Mol Neurobiol Unit, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Bai, G (reprint author), Brigham & Womens Hosp, CNS Res Inst, LMRC, Rm LM111,221 Longwood Ave, Boston, MA 02115 USA. EM gbai@rics.bhw.harvard.edu NR 42 TC 49 Z9 49 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 JAN 9 PY 1998 VL 273 IS 2 BP 1086 EP 1091 DI 10.1074/jbc.273.2.1086 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400062 PM 9422773 ER PT J AU Putney, JW AF Putney, JW TI Calcium signaling: Up, down, up, down ... What's the point? SO SCIENCE LA English DT Article ID DEPENDENT PROTEIN-KINASE; CALMODULIN; AUTOPHOSPHORYLATION; OSCILLATIONS C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 11 TC 80 Z9 80 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 9 PY 1998 VL 279 IS 5348 BP 191 EP 192 DI 10.1126/science.279.5348.191 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ636 UT WOS:000071408100030 PM 9446226 ER PT J AU Gannon, PJ Holloway, RL Broadfield, DC Braun, AR AF Gannon, PJ Holloway, RL Broadfield, DC Braun, AR TI Asymmetry of chimpanzee planum temporale: Humanlike pattern of Wernicke's brain language area homolog SO SCIENCE LA English DT Article ID CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; RHESUS-MONKEYS; ASSOCIATIONS; HYPOTHESIS; PATHOLOGY; PROGRAM; ORGANIZATION; REGION AB The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (Pan troglodytes). The left planum temperate was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago. C1 CUNY Mt Sinai Sch Med, Dept Otolaryngol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. Columbia Univ, Dept Anthropol, New York, NY 10027 USA. CUNY, Dept Anthropol, New York, NY 10036 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Gannon, PJ (reprint author), CUNY Mt Sinai Sch Med, Dept Otolaryngol, Box 1189,5th Ave & 100th St, New York, NY 10029 USA. EM P_Gannon@smtplink.mssm.edu NR 50 TC 277 Z9 280 U1 3 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 9 PY 1998 VL 279 IS 5348 BP 220 EP 222 DI 10.1126/science.279.5348.220 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ636 UT WOS:000071408100040 PM 9422693 ER PT J AU Hakim, AA Petrovitch, H Burchfiel, CM Ross, GW Rodriguez, BL White, LR Yano, K Curb, JD Abbott, RD AF Hakim, AA Petrovitch, H Burchfiel, CM Ross, GW Rodriguez, BL White, LR Yano, K Curb, JD Abbott, RD TI Effects of walking on mortality among nonsmoking retired men SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; MIDDLE-AGED MEN; PHYSICAL-ACTIVITY; JAPANESE MEN; PROGRAM; RISK; DIETARY; STROKE; HAWAII; WEIGHT AB Background The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis. Methods We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up. Results During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P = 0.01). Conclusions Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate, Encouraging elderly people to walk may benefit their health. (C) 1998, Massachusetts Medical Society. C1 Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA 22908 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96817 USA. NHLBI, Honolulu Epidemiol Res Sect, Epidemiol & Biometry Program, Honolulu, HI USA. Dept Vet Affairs, Honolulu, HI USA. NIA, Honolulu, HI USA. RP Abbott, RD (reprint author), Univ Virginia, Sch Med, Div Biostat, Box 600, Charlottesville, VA 22908 USA. FU NCRR NIH HHS [P20 RR/AI 11091]; NHLBI NIH HHS [N01-HC-05102] NR 21 TC 319 Z9 323 U1 0 U2 9 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 1998 VL 338 IS 2 BP 94 EP 99 DI 10.1056/NEJM199801083380204 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YQ039 UT WOS:000071341300004 PM 9420340 ER PT J AU Wang, QJ Acs, P Goodnight, JA Blumberg, PM Mischak, H Mushinski, JF AF Wang, QJ Acs, P Goodnight, JA Blumberg, PM Mischak, H Mushinski, JF TI The catalytic domain of PKC-epsilon, in reciprocal PKC-delta and -epsilon chimeras, is responsible for conferring tumorgenicity to NIH3T3 cells, whereas both regulatory and catalytic domains of PKC-epsilon contribute to in vitro transformation SO ONCOGENE LA English DT Article DE chimeric PKC; PKC-epsilon; PKC-delta; transformation; tumorgenicity; NIH3T3 ID PROTEIN-KINASE-C; FIBROBLASTS; NUCLEAR; ISOFORM; RAS AB Protein kinase C-epsilon (PKC-epsilon) has been shown to increase growth and cause malignant transformation when overexpressed in NIH3T3 cells, whereas PKC-delta reduced fibroblast growth, Two reciprocal chimeric proteins (PKC-epsilon delta and PKC-delta epsilon were constructed by exchanging the regulatory and catalytic domains of PKC-delta and -epsilon and were stably overexpressed in NIH3T3 cells, Fibroblasts that overexpressed either chimera showed maximum cell density and morphology that were intermediate between cells overexpressing PKC-delta and those that overexpressed PKC-epsilon, Moreover, all lines that expressed chimeras were capable of anchorage-independent growth in the presence of TPA, which indicated that both the regulatory and catalytic domains of PKC-epsilon could independently induce NIH3T3 transformation, although the combination of both domains, as found in PKC-epsilon, was the most active form, In contrast, the translocation pattern and ability to induce tumors in nude mice was attributable to the catalytic domains exclusively, In particular, cells that expressed PKC-delta epsilon retained PKC-epsilon's full potency of tumorgenicity when injected into nude mice, In sum, our findings not only reinforce the concept that only certain PKC isozymes contribute to carcinogenesis but also show that different domains of PKCs mediate the physiologically distinguishable events of transformation and tumorgenesis. C1 NCI, Genet Lab, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Mushinski, JF (reprint author), NCI, Genet Lab, Bethesda, MD 20892 USA. RI Mischak, Harald/E-8685-2011; Wang, Qiming/B-6064-2012 NR 15 TC 18 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 8 PY 1998 VL 16 IS 1 BP 53 EP 60 DI 10.1038/sj.onc.1201507 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YP056 UT WOS:000071236800006 PM 9467942 ER PT J AU Blackshear, PE Goldsworthy, SM Foley, JF McAllister, KA Bennett, LM Collins, NK Bunch, DO Brown, P Wiseman, RW Davis, BJ AF Blackshear, PE Goldsworthy, SM Foley, JF McAllister, KA Bennett, LM Collins, NK Bunch, DO Brown, P Wiseman, RW Davis, BJ TI Brca1 and Brca2 expression patterns in mitotic and meiotic cells of mice. SO ONCOGENE LA English DT Article DE Brca1; Brca2; mitosis; meiosis ID BREAST-CANCER; SPERMATOGENIC CELLS; EPITHELIAL-CELLS; MESSENGER-RNA; GENE; DIFFERENTIATION; SUSCEPTIBILITY; TISSUES AB The mouse homologues of the breast cancer susceptibility genes, Brca1 and Brca2, are expressed in a cell cycle-dependent fashion in vitro and appear to be regulated by similar or overlapping pathways, Therefore, we compared the non isotopic in situ hybridization expression patterns of Brca1 and Brca2 mRNA in vivo in mitotic and meiotic cells during mouse embryogenesis, mammary gland development, and in adult tissues including testes, ovaries, and hormonally altered ovaries, Brca1 and Brca2 are expressed concordantly in proliferating cells of embryos, and the mammary gland undergoing morphogenesis and in most adult tissues, The expression pattern of Brca1 and Brca2 correlates with the localization of proliferating cell nuclear antigen, an indicator of proliferative activity, In the ovary, Brca1 and Brca2 exhibited a comparable hormone-independent pattern of expression in oocytes, granulosa cells and thecal cells of developing follicles, In the testes, Brca1 and Brca2 were expressed in mitotic spermatogonia and early meiotic prophase spermatocytes, Northern analyses of prepubertal mouse testes revealed that the time course of Brca2 expression was delayed in spermatogonia relative to Brca1. Thus, while Brca1 and Brca2 share concordant cell-specific patterns of expression in most proliferating tissues, these observations suggest that they may have distinct roles during meiosis. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Pathol Associates Int, Durham, NC 27713 USA. RP Blackshear, PE (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 70 Z9 71 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 8 PY 1998 VL 16 IS 1 BP 61 EP 68 DI 10.1038/sj.onc.1201506 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YP056 UT WOS:000071236800007 PM 9467943 ER PT J AU Albert, CM Hennekens, CH O'Donnell, CJ Ajani, UA Carey, VJ Willett, WC Ruskin, JN Manson, JE AF Albert, CM Hennekens, CH O'Donnell, CJ Ajani, UA Carey, VJ Willett, WC Ruskin, JN Manson, JE TI Fish consumption and risk of sudden cardiac death SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; POLYUNSATURATED FATTY-ACIDS; VENTRICULAR-FIBRILLATION; MYOCARDIAL-INFARCTION; MORTALITY; OMEGA-3-FATTY-ACIDS; REPRODUCIBILITY; POPULATION; PHYSICIANS AB Context.-Dietary fish intake has been associated with a reduced risk of fatal cardiac end points, but not with nonfatal end points. Dietary fish intake may have a selective benefit on fatal arrhythmias and therefore sudden cardiac death. Objective.-To investigate prospectively the association between fish consumption and the risk of sudden cardiac death. Design.-Prospective cohort study. Setting.-The US Physicians' Health Study. Patients.-A total of 20 551 US male physicians 40 to 84 years of age and free of myocardial infarction, cerebrovascular disease, and cancer at baseline who completed an abbreviated, semiquantitative food frequency questionnaire on fish consumption and were then followed up to 11 years. Main Outcome Measure.-Incidence of sudden cardiac death (death within 1 hour of symptom onset) as ascertained by hospital records and reports of next of kin. Results.-There were 133 sudden deaths over the course of the study. After controlling for age, randomized aspirin and beta carotene assignment, and coronary risk factors, dietary fish intake was associated with a reduced risk of sudden death, with an apparent threshold effect at a consumption level of 1 fish meal per week (P for trend=.03). For men who consumed fish at least once per week, the multivariate relative risk of sudden death was 0.48 (95% confidence interval, 0.24-0.96; P=.04) compared with men who consumed fish less than monthly. Estimated dietary n-3 fatty acid intake from seafood also was associated with a reduced risk of sudden death but without a significant trend across increasing categories of intake. Neither dietary fish consumption nor n-3 fatty acid intake was associated with a reduced risk of total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality. However, fish consumption was associated with a significantly reduced risk of total mortality. Conclusion.-These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-34944, CA-40360]; NHLBI NIH HHS [HL-26490] NR 41 TC 592 Z9 607 U1 2 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 1998 VL 279 IS 1 BP 23 EP 28 DI 10.1001/jama.279.1.23 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100030 PM 9424039 ER PT J AU Wood, D Halfon, N Donald-Sherbourne, C Mazel, RM Schuster, M Hamlin, JS Pereyra, M Camp, P Grabowsky, M Duan, NH AF Wood, D Halfon, N Donald-Sherbourne, C Mazel, RM Schuster, M Hamlin, JS Pereyra, M Camp, P Grabowsky, M Duan, NH TI Increasing immunization rates among inner-city, African American children - A randomized trial of case management SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RISK-FACTORS; DELAYED IMMUNIZATION; COVERAGE AB Context.-Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested. Objective.-To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families. Design.-Randomized controlled trial with follow-up through 1 year of life. Setting.-Low-income areas of inner-city Los Angeles, Calif. Patients.-A representative sample of 419 African American infants and their families. Interventions.-In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed. Main Outcome Measures.-Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention. Results.-A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12 022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits. Conclusions.-A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed. C1 Shriners Hosp, Dept Pediat, Tampa, FL 33631 USA. Rand Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. NIH, Vaccine & Prevent Res Branch, Div Aids, Bethesda, MD USA. RP Wood, D (reprint author), Shriners Hosp, Dept Pediat, POB 31356, Tampa, FL 33631 USA. FU PHS HHS [200-91-0942] NR 32 TC 71 Z9 71 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 1998 VL 279 IS 1 BP 29 EP 34 DI 10.1001/jama.279.1.29 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100031 PM 9424040 ER PT J AU Takayama, S Sieber, SM Adamson, RH Thorgeirsson, UP Dalgard, DW Arnold, LL Cano, M Eklund, S Cohen, SM AF Takayama, S Sieber, SM Adamson, RH Thorgeirsson, UP Dalgard, DW Arnold, LL Cano, M Eklund, S Cohen, SM TI Long-term feeding of sodium saccharin to nonhuman primates: Implications for urinary tract cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Cancer-Research CY APR 20-24, 1996 CL WASHINGTON, D.C. SP Amer Assoc Canc Res ID SCANNING ELECTRON-MICROSCOPY; ARTIFICIAL SWEETENERS; BLADDER-CANCER; MALE-RAT; CARCINOGENESIS; PROTEINS AB Background: It was observed in the early 1970s that saccharin produced bladder cancer in rats, However, it has been unclear whether sodium saccharin when consumed by humans poses a substantial carcinogenic hazard, Numerous epidemiologic studies have not shown any evidence of increased urothelial proliferation associated with ingestion of sodium saccharin, Purpose: Our purpose was to determine the effects of long-term feeding of sodium saccharin to three species of nonhuman primates, Methods: Twenty monkeys of three species (six African green, seven rhesus, six cynomolgus, and one hybrid [of rhesus male and cynomolgus female parentage]) were treated with sodium saccharin (25 mg in the diet/kg body weight daily for 5 days a week) beginning within 24 hours after birth and continuing for up to 24 years, Sixteen monkeys (seven rhesus and nine cynomolgus) served as controls, During their last 2 years of life, urine was collected from selected treated and control animals and evaluated for various urinary chemistries and for the presence of calculi, microcrystalluria, and precipitate, Urinary bladders were examined by light microscopy and by scanning electron microscopy, Results: Sodium saccharin treatment had no effect on the urine or urothelium in any of these monkeys, There was no evidence of increased urothelial cell proliferation, and there was no evidence of formation of solid material in the urine, Conclusion: Although the dose of sodium saccharin administered to these monkeys was only five to 10 times the allowable daily intake for humans, the results provide additional evidence that sodium saccharin is without a carcinogenic effect on the primate urinary tract. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Covance Labs Inc, Vienna, VA USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Eppley Inst, Omaha, NE 68198 USA. RP Thorgeirsson, UP (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Rm 2D-02, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA36727, CA32513] NR 33 TC 29 Z9 31 U1 1 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 JAN 7 PY 1998 VL 90 IS 1 BP 19 EP 25 DI 10.1093/jnci/90.1.19 PG 7 WC Oncology SC Oncology GA YX072 UT WOS:000072003600008 PM 9428778 ER PT J AU Bradlow, HL Davis, D Pearson, C Ragovin, C Sekely, L Sieber, SM Soto, A AF Bradlow, HL Davis, D Pearson, C Ragovin, C Sekely, L Sieber, SM Soto, A TI Workshop on hormones, hormone metabolism, the environment, and breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Strang Cornell Res Lab, New York, NY USA. World Resources Inst, Washington, DC 20006 USA. Natl Womens Hlth Network, Washington, DC USA. Massachusetts Breast Canc Coalit, Weston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Sieber, SM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 JAN 7 PY 1998 VL 90 IS 1 BP 67 EP 67 DI 10.1093/jnci/90.1.67 PG 1 WC Oncology SC Oncology GA YX072 UT WOS:000072003600016 PM 9428786 ER PT J AU Puri, A Hug, P Munoz-Barroso, I Blumenthal, R AF Puri, A Hug, P Munoz-Barroso, I Blumenthal, R TI Human erythrocyte glycolipids promote HIV-1 envelope glycoprotein-mediated fusion of CD4(+) cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SEMLIKI FOREST VIRUS; MEMBRANE-FUSION; CD4-DEPENDENT FUSION; RESISTANT FACTORS; PLASMA-MEMBRANE; RECEPTOR; ENTRY; OLIGOSACCHARIDES; INFECTION AB We examined the role of target membrane glycolipids in CD4-mediated HIV-1 fusion by altering the glycolipid levels in CD4(+) cells. CD4(+) human cells exhibited 50% reduction in extent of fusion with gp120-gp41 expressing cells (TF228) when grown in the presence of a glycolipid synthesis inhibitor PPMP. We added erythrocyte glycolipids (GL) to fusion-incompetent CD4(+) non-human cells by influenza-hemagglutinin-mediated fusion between GL-containing liposomes and target cells. Human erythrocyte GL (HuGL)-modified CD4(+) non-human cells became susceptible to fusion with TF228 cells. Transfer of bovine erythrocyte glycolipids (BoGL) to CD4(+) non-human cells under similar conditions did not complement HIV-1 fusion, Furthermore, addition of HuGL, but not BoGL, to PPMP-inhibited cells rescued fusion to the original levels. Our observations demonstrate that human erythrocyte glycolipids promote CD4-mediated HIV-1 fusion and certain glycolipid(s) from human erythrocytes may serve as alternative and/or additional cofactors in HIV-1 entry. (C) 1998 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Sect Membrane Struct & Funct, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Sect Membrane Struct & Funct, POB B,Bldg 469,Room 213,Miller Dr, Frederick, MD 21702 USA. NR 26 TC 28 Z9 28 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 JAN 6 PY 1998 VL 242 IS 1 BP 219 EP 225 DI 10.1006/bbrc.1997.7941 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YR970 UT WOS:000071550600040 PM 9439639 ER PT J AU Cho, JJ Vliagoftis, H Rumsaeng, V Metcalfe, DD Oh, CK AF Cho, JJ Vliagoftis, H Rumsaeng, V Metcalfe, DD Oh, CK TI Identification and categorization of inducible mast cell genes in a subtraction library SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA; CDNA LIBRARY; T-CELLS; ACTIVATION; IGE; EOSINOPHILS; FIBROBLASTS; EXPRESSION; LINE AB Mast cells play an important role in allergic inflammation by releasing inducible proinflammatory cytokines. While many inducible genes have been identified, we hypothesized that a significant number remain to be identified. We thus constructed an activation-specific mast cell subtraction library to establish a profile of induced genes in mast cells following allergic simulation. To date, we have sequenced 150 cDNA clones. Among them, we have isolated 22 known genes whose expression has not been reported in mast cells, and an additional 26 cDNA clones which do not have significant homology to known genes in the Genbank database. We next selected 10 cDNA clones with strong signals by differential plaque hybridization. Of these cDNA clones, five genes were induced in mast cells upon Fc epsilon RI-mediated stimulation. They are cofilin, annexinVI, interferon (IFN)-beta, serglycin, and a novel inducible mast cell (IMC) gene, IMC-415. Characterization and relevant studies of this novel gene and other inducible known genes in mast cells will provide insight into the functions of mast cells in mammalian biology. (C) 1998 Academic Press. C1 Univ Calif Los Angeles, Harbor Med Ctr, Dept Pediat, Div Allergy & Immunol, Torrance, CA 90502 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Oh, CK (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Dept Pediat, Div Allergy & Immunol, Torrance, CA 90502 USA. RI Vliagoftis, Harissios/C-6480-2013 NR 21 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 6 PY 1998 VL 242 IS 1 BP 226 EP 230 DI 10.1006/bbrc.1997.7644 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YR970 UT WOS:000071550600041 PM 9439640 ER PT J AU Duhe, RJ Evans, GA Erwin, RA Kirken, RA Cox, GW Farrar, WL AF Duhe, RJ Evans, GA Erwin, RA Kirken, RA Cox, GW Farrar, WL TI Nitric oxide and thiol redox regulation of Janus kinase activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-TYROSINE KINASE; NF-KAPPA-B; 3-DIMENSIONAL SOLUTION STRUCTURE; HUMAN-IMMUNODEFICIENCY-VIRUS; SIGNAL-TRANSDUCTION PATHWAY; LEUKEMIA-DERIVED FACTOR; T-CELL PROLIFERATION; HUMAN INTERLEUKIN-3; SECONDARY STRUCTURE; LYMPHOCYTE-PROLIFERATION AB The activation of Janus kinases (JAKs) is crucial for propagation of the proliferative response initiated by many cytokines. The proliferation of various cell lines, particularly those of hematopoietic origin, is also modulated by mediators of oxidative stress such as nitric oxide and thiol redox reagents. Herein we demonstrate that nitric oxide and other thiol oxidants can inhibit the autokinase activity of rat JAK2 in vitro, presumably through oxidation of crucial dithiols to disulfides within JAK2. The reduced form of JAK2 is the most active form, and the oxidized JAK2 form is inactive. Nitric oxide pretreatment of quiescent Ba/F3 cells also inhibits the interleukin 3-triggered in vivo activation of JAK2, a phenomenon that correlates with inhibited proliferation. Furthermore, we observed that the autokinase activity of JAK3 responds in a similar fashion to thiol redox reagents irt vitro and to nitric oxide donors in vivo. We suggest that the thiol redox regulation of JAKs may partially explain the generally immunosuppressive effects of nitric oxide and of other thiol oxidants. C1 Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. NCI, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Duhe, RJ (reprint author), Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NR 77 TC 113 Z9 117 U1 1 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 JAN 6 PY 1998 VL 95 IS 1 BP 126 EP 131 DI 10.1073/pnas.95.1.126 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500028 PM 9419340 ER PT J AU Martinez-Balbas, MA Tsukiyama, T Gdula, D Wu, C AF Martinez-Balbas, MA Tsukiyama, T Gdula, D Wu, C TI Drosophila NURF-55, a WD repeat protein involved in histone metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEOSOME REMODELING FACTOR; NEGATIVE REGULATOR; CHROMATIN; FAMILY; TRANSCRIPTION; EMBRYOS; YEAST; ACETYLTRANSFERASE; ACETYLATION; COMPLEX AB The Drosophila nucleosome remodeling factor (NURF) is a protein complex of four distinct subunits that assists transcription factor-mediated chromatin remodeling. One NURF subunit, ISWI, is related to the transcriptional regulators Drosophila brahma and yeast SW12/SNF2. We have determined peptide sequences and isolated cDNA clones for a second NURF component (the 55-kDa subunit). Immunological studies show that p55 is an integral subunit of NURF and is generally associated with polytene chromosomes. The predicted sequence of p55 reveals a WD repeat protein that is identical with the 55-kDa subunit of the Drosophila chromatin assembly factor (CAF-1). Given that WD repeat proteins related to p55 are associated with histone deacetylase and histone acetyltransferase, our findings suggest that p55 and its homologs may function as a common platform for the assembly of protein complexes involved in chromatin metabolism. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 5E-26, Bethesda, MD 20892 USA. OI Martinez-Balbas, Marian/0000-0003-0173-0964 NR 32 TC 132 Z9 134 U1 2 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 JAN 6 PY 1998 VL 95 IS 1 BP 132 EP 137 DI 10.1073/pnas.95.1.132 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500029 PM 9419341 ER PT J AU Huang, CS Ma, WY Young, MR Colburn, N Dong, ZG AF Huang, CS Ma, WY Young, MR Colburn, N Dong, ZG TI Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROMOTER-INDUCED TRANSFORMATION; C-JUN; EPIDERMAL-CELLS; NEOPLASTIC TRANSFORMATION; TUMOR PROMOTERS; PHORBOL ESTERS; EXPRESSION; GROWTH; CARCINOGENESIS; REQUIREMENT AB The JB6 mouse epidermal cell system, which includes tumor promotion-sensitive (P+) and tumor promotion-resistant (P-) cells, is a well-established and extensively used cell culture model for studying the mechanism of late-stage tumor promotion, Tumor promoters, such as 12-O-tetradecanoylphorbol 13-acetate (TPA) or epidermal growth factor (EGF), induce high levels of activator protein 1 (AP-1) activity and large, tumorigenic, anchorage-independent colonies in soft agar at a high frequency in JB6 P+ cells, but not in JB6 P- cells, We report here a molecular explanation for the defect in the AP-1 activation and promotion-resistant phenotype of P- cells, We demonstrate that the lack of AP-1 activation and cell transformation responses to TPA and EGF in P- cells appears attributable to the low level of mitogen-activated protein kinase (MAPK) (extracellular signal-regulated protein kinase, Erk) in these cells, TPA and EGF induce transactivation of AP-1 activity in pf cells but not in P- cells, Nonphosphorylated forms and TPA- or EGF-induced phosphorylated forms of Erks (Erk1 and Erk2) in P- cells were much lower than those in P+ cells. Stable transfection of wild-type MAPK (Erk2) into P- cells restored its response to TPA and EGF for both AP-1 activation and cell transformation, These results suggest that the shortage of MAPK (Erk1 and Erk2) appears to be an important contributor to the tumor promotion-resistant phenotype in JB6 cells. C1 Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NCI, Gene Regulat Sect, Biochem Physiol Lab, Frederick Canc Res Facil, Frederick, MD 21702 USA. RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, 801 16Th Ave NE, Austin, MN 55912 USA. FU NCI NIH HHS [CA74916] NR 40 TC 178 Z9 183 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 JAN 6 PY 1998 VL 95 IS 1 BP 156 EP 161 DI 10.1073/pnas.95.1.156 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500033 PM 9419345 ER PT J AU Patel, BKR Pierce, JH LaRochelle, WJ AF Patel, BKR Pierce, JH LaRochelle, WJ TI Regulation of interleukin 4-mediated signaling by naturally occurring dominant negative and attenuated forms of human Stat6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STIMULATORY FACTOR-I; JAK-3 JANUS KINASE; DNA-BINDING; TYROSINE PHOSPHORYLATION; RECEPTOR EXPRESSION; HEMATOPOIETIC-CELLS; COMMON ELEMENTS; IL-4 RECEPTOR; MYELOID CELLS; GROWTH-FACTOR AB Interleukin (IL)-4-mediated nuclear signaling by Stat6 has been implicated in lymphoid cell proliferation and the transcriptional activation of genes encoding major histocompatability complex (MHC) class II molecules and Fc receptors, To investigate IL-4-mediated transcriptional events, we cloned two naturally occurring human Stat6 iso forms, Stat6b and Stat6c, that encoded an NH2-terminal truncation or an SH2 domain deletion, respectively, Stat6 variant mRNAs were differentially expressed in many human tissues, To elucidate the biologic role of each isoform, we examined the consequences of overexpression in IL-4-responsive FDC-P2 cells, Stat6 and Stat6b (to a lesser extent) enhanced DNA synthesis, up-regulated endogenous MHC class II and Fc gamma receptors, and became tyrosine phosphorylated in response to IL-4 stimulation, In contrast, Stat6c, which lacks functionally critical SH2 domain residues, unexpectedly inhibited IL-4-mediated mitogenesis and cell surface antigen expression and was not tyrosine phosphorylated, Although Stat6c only modestly diminished endogenous Stat6 tyrosine phosphorylation, it abolished endogenous Stat6 Fc gamma RI and I epsilon DNA binding activity and Fc gamma RI-luciferase reporter transcriptional activation, Our results indicate that the molecular mechanism of inhibition by Stat6c was due to suppression of endogenous Stat6 dimer formation. Thus, Stat6b and Stat6c are naturally occurring attenuated and dominant negative Stat6 variants, respectively, that affect IL-4-mediated biologic responses through differential transcriptional regulation. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP LaRochelle, WJ (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 1E24, Bethesda, MD 20892 USA. NR 37 TC 45 Z9 45 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 JAN 6 PY 1998 VL 95 IS 1 BP 172 EP 177 DI 10.1073/pnas.95.1.172 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500036 PM 9419348 ER PT J AU Amoroso, SR Huang, NH Roberts, AB Potter, M Letterio, JJ AF Amoroso, SR Huang, NH Roberts, AB Potter, M Letterio, JJ TI Consistent loss of functional transforming growth factor beta receptor expression in murine plasmacytomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERLEUKIN-6 TRANSGENIC MICE; TGF-BETA; II RECEPTOR; CANCER CELLS; CARCINOMA-CELLS; LYMPHOCYTES-B; PLASMA-CELLS; GENE; APOPTOSIS; LYMPHOMA AB Murine plasmacytomas are tumors of Ig-secreting plasma cells that can be induced in genetically susceptible BALB/c mice. The deregulation of the c-myc protooncogene is a critical oncogenic event in the development of plasmacytomas (Pers) although it is not sufficient for their malignant transformation. We have demonstrated that PCTs produce active transforming growth factor beta (TGF-beta) in vitro. Because TGF-beta is a potent negative regulator of the proliferation and differentiation of B lymphocytes, we examined its role in plasmacytomagenesis by comparing responsiveness to TGF-beta of nonneoplastic plasma cells and PCTs. The nontransformed plasma cells that accumulate in interleukin 6 transgenic mice undergo accelerated apoptosis upon treatment with TGF-beta, but the 15 PCTs studied, including primary and transplanted tumors as well as established cell lines, were refractory to TGF-beta-mediated growth inhibition and apoptosis, Although PCTs lack functional TGF-beta receptors as demonstrated by chemical crosslinking to radiolabeled TGF-beta 1, they nonetheless contain mRNA and protein for both type I and II TGF-beta receptors, suggesting a potential defect in receptor trafficking or processing. The results clearly show the consistent inactivation of TGF-beta receptors in plasmacytoma cells, demonstrating for the first time that interruption of a tumor suppressor pathway contributes to plasmacytomagenesis. C1 NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Cell & Mol Biol Program, College Pk, MD 20742 USA. RP Letterio, JJ (reprint author), NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. NR 46 TC 39 Z9 42 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 JAN 6 PY 1998 VL 95 IS 1 BP 189 EP 194 DI 10.1073/pnas.95.1.189 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500039 PM 9419351 ER PT J AU Roger, AJ Svard, SG Tovar, J Clark, CG Smith, MW Gillin, FD Sogin, ML AF Roger, AJ Svard, SG Tovar, J Clark, CG Smith, MW Gillin, FD Sogin, ML TI A mitochondrial-like chaperonin 60 gene in Giardia lamblia: Evidence that diplomonads once harbored an endosymbiont related to the progenitor of mitochondria SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEAT-SHOCK; ORIGIN; PROTEIN; EVOLUTION; DUODENALIS; PROTOZOA; TREE; LIFE; RNA AB Diplomonads, parabasalids, as represented by trichomonads, and microsporidia are three protist lineages lacking mitochondria that branch earlier than all other eukaryotes in small subunit rRNA and elongation factor phylogenies, The absence of mitochondria and plastids in these organisms suggested that they diverged before the origin of these organelles, However, recent discoveries of mitochondrial-like heat shock protein 70 and/or chaperonin 60 (cpn60) genes in trichomonads and microsporidia imply that the ancestors of these two groups once harbored mitochondria or their endosymbiotic progenitors, In this report, we describe a mitochondrial-like cpn60 homolog from the diplomonad parasite Giardia lamblia. Northern and Western blots reveal that the expression of cpn60 is independent of cellular stress and, except during excystation, occurs throughout the G. lamblia life cycle, Phylogenetic analyses position the G. lamblia cpn60 in a clade that includes mitochondrial and hydrogenosomal cpn60 proteins, The most parsimonious interpretation of these data is that the cpn60 gene was transferred from the endosymbiotic ancestors of mitochondria to the nucleus early in eukaryotic evolution, before the divergence of the diplomonads and trichomonads from other extant eukaryotic lineages, A more complicated explanation requires that these genes originated from distinct alpha-proteobacterial endosymbioses that formed transiently within these protist lineages. C1 Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. Univ Calif San Diego, Med Ctr, Dept Pathol, San Diego, CA 92103 USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Sogin, ML (reprint author), Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. EM sogin@evo15.mbl.edu RI Clark, C Graham/H-3683-2011; Smith, Michael/B-5341-2012 OI Clark, C Graham/0000-0002-0521-0977; FU NIAID NIH HHS [AI24285]; NIDDK NIH HHS [P01 DK035108, DK35108]; NIGMS NIH HHS [GM53835]; Wellcome Trust NR 49 TC 226 Z9 234 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 JAN 6 PY 1998 VL 95 IS 1 BP 229 EP 234 DI 10.1073/pnas.95.1.229 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500046 PM 9419358 ER PT J AU Muller, S Margolin, DH Nara, PL Alvord, WG Kohler, H AF Muller, S Margolin, DH Nara, PL Alvord, WG Kohler, H TI Stimulation of HIV-1-neutralizing antibodies in simian HIV-IIIB-infected macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; rhesus macaque; virus neutralization ID ANTI-GP120 ANTIBODIES; IMMUNE-RESPONSE; SPECIFICITY; INDIVIDUALS; AIDS AB Previously we have discovered a public idiotope, designated 1F7, that is expressed on antibodies against HIV type 1 (HIV-1) in human and nonhuman primates, To test the potential of mouse monoclonal antibody (mAb) 1F7 as a therapeutic anti-clonotypic antibody in HIV-1-infected patients, we used the simian HIV-IIIB macaque infection model, which mimics several immunological and pathological characteristics of HIV-1 infection in humans, Four healthy simian HIV-infected rhesus monkeys (Macaca mulatta) expressing the 1F7 marker on anti-gp120 antibodies were selected for this study, Three monkeys of this group were immunized several times with the murine mAb 1F7 i.v., and one monkey received as control an isotype-matched antibody, TEPC183, No serious side effect or allergic reaction was encountered, Blood collected before and during the immunization and over several months afterward were analyzed for neutralizing antibodies, Significant increases in breadth and potency of HIV-1-neutralizing antibody titers to one or more virus strains were detected in all three of the 1F7-immunized monkeys, but not in the control monkey immunized with TEPC183, These results show that an antibody, recognizing a public idiotope associated with anti-HIV-1 antibodies can function in chronically infected primates as an anti-clonotypic immunogen to boost antibodies that neutralize homologous and heterologous virus strains, This study represents a first step toward the preclinical evaluation of 1F7 as a therapeutic AIDS vaccine. C1 Immpheron Inc, Lexington, KY 40509 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NCI, Frederick, MD 21702 USA. Univ Kentucky, Lexington, KY 40536 USA. RP Muller, S (reprint author), Immpheron Inc, 5235 Athens Boonesboro Rd, Lexington, KY 40509 USA. EM Immpheron@aol.com FU NIAID NIH HHS [AI-07387, T32 AI007387] NR 23 TC 17 Z9 18 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 JAN 6 PY 1998 VL 95 IS 1 BP 276 EP 281 DI 10.1073/pnas.95.1.276 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500054 PM 9419366 ER PT J AU Vasmatzis, G Essand, M Brinkmann, U Lee, B Pastan, I AF Vasmatzis, G Essand, M Brinkmann, U Lee, B Pastan, I TI Discovery of three genes specifically expressed in human prostate by expressed sequence tag database analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article AB A procedure is described to discover genes that are specifically expressed in human prostate, The procedure involves searching the expressed sequence tag (EST) database for genes that have many related EST sequences from human prostate cDNA libraries but none or few from nonprostate human libraries, The selected candidate EST clones were tested by RNA dot blots to examine tissue specificity and by Northern blots to examine the transcript size of the corresponding mRNA. The computer analysis identified 15 promising genes that were previously unidentified. When seven of these were examined in an RNA hybridization experiment, three were found to be prostate specific, The genes identified could be useful in the targeted therapy of prostate cancer. The procedure can easily be applied to discover genes specifically expressed in other organs or tumors. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 6 TC 130 Z9 138 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 JAN 6 PY 1998 VL 95 IS 1 BP 300 EP 304 DI 10.1073/pnas.95.1.300 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500058 PM 9419370 ER PT J AU Wen, XL Fuhrman, S Michaels, GS Carr, DB Smith, S Barker, JL Somogyi, R AF Wen, XL Fuhrman, S Michaels, GS Carr, DB Smith, S Barker, JL Somogyi, R TI Large-scale temporal gene expression mapping of central nervous system development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA AB We used reverse transcription-coupled PCR to produce a high-resolution temporal map of fluctuations in mRNA expression of 112 genes during rat central nervous system development, focusing on the cervical spinal cord, The data provide a temporal gene expression "fingerprint" of spinal cord development based on major families of inter- and intracellular signaling genes, By using distance matrices for the pair-wise comparison of these 112 temporal gene expression patterns as the basis for a cluster analysis, we found five basic "waves" of expression that characterize distinct phases of development, The results suggest functional relationships among the genes fluctuating in parallel. We found that genes belonging to distinct functional classes and gene families clearly map to particular expression profiles, The concepts and data analysis discussed herein may be useful in objectively identifying coherent patterns and sequences of events in the complex genetic signaling network of development. Functional genomics approaches such as this may have applications in the elucidation of complex developmental and degenerative disorders. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. George Mason Univ, Inst Computat Sci & Informat, Fairfax, VA 22030 USA. RP Somogyi, R (reprint author), NINDS, Neurophysiol Lab, NIH, 36 2C02, Bethesda, MD 20892 USA. EM rolands@helix.nih.gov NR 21 TC 409 Z9 425 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 JAN 6 PY 1998 VL 95 IS 1 BP 334 EP 339 DI 10.1073/pnas.95.1.334 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500064 PM 9419376 ER PT J AU vandeWalle, M Shiloach, J AF vandeWalle, M Shiloach, J TI Proposed mechanism of acetate accumulation in two recombinant Escherichia coli strains during high density fermentation SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE acetate; E-coli; metabolic flux ID FED-BATCH FERMENTATIONS; PROTEIN-PRODUCTION; METABOLIC FLUXES; BRANCH POINT; GROWTH-RATE; EXCRETION; CULTURES AB The productivity of Escherichia coli as a producer of recombinant proteins is affected by its metabolic properties, especially by acetate production. Two commercially used E. coli strains, BL21 (lambda DE3) and JM109, differ significantly in their acetate production during batch fermentation at high initial glucose concentrations. E. coli BL21 grows to an optical density (OD, 600 nm) of 100 and produces no more than 2 g/L acetate, while E. coli JM109 grows to an OD (600 nm) of 80 and produces up to 14 g/L acetate. Even in fed-batch fermentation, when glucose concentration is maintained between 0.5 and 1.0 g/L, JM109 accumulates 4 times more acetate than BL21. To investigate the difference between the two strains, metabolites and enzymes involved in carbon utilization and acetate production were analyzed (isocitrate, ATP, phosphoenolpyruvate, pyruvate, isocitrate lyase, and isocitrate dehydrogenase). The results showed that during batch fermentation isocitrate lyase activity and isocitrate concentration were higher in BL21 than in JM109, while pyruvate concentration was higher in JM109. The activation of the glyoxylate shunt pathway at high glucose concentrations is suggested as a possible explanation for the lower acetate accumulation in E. coli BL21. Metabolic flux analysis of the batch cultures supports the activity of the glyoxylate shunt in E. coli BL21. (C) 1998 John Wiley & Sons, Inc. C1 NIDDK, BIOTECHNOL UNIT, LCDB, NIH, BETHESDA, MD 20892 USA. NR 30 TC 66 Z9 67 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 EI 1097-0290 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JAN 5 PY 1998 VL 57 IS 1 BP 71 EP 78 DI 10.1002/(SICI)1097-0290(19980105)57:1<71::AID-BIT9>3.0.CO;2-S PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YH990 UT WOS:A1998YH99000009 PM 10099180 ER PT J AU Giannakakou, P Villalba, L Li, H Poruchynsky, M Fojo, T AF Giannakakou, P Villalba, L Li, H Poruchynsky, M Fojo, T TI Combinations of paclitaxel and vinblastine and their effects on tubulin polymerization and cellular cytotoxicity: Characterization of a synergistic schedule SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TAXOL; PROTEINS; AGENTS; LINES AB Paclitaxel (PTX) and vinblastine (VBL) represent 2 classes of drugs that target tubulin but have separate binding properties and opposing mechanisms of action. To evaluate the potential use of these agents together in a chemotherapeutic regimen, we investigated their effects on the dynamics of tubulin polymerization and cellular cytotoxicity, when administered singly or in combination. In human epidermoid carcinoma KB cells and MCF-7 breast carcinoma cells, we observed a time-and dose dependent effect on cytoskeletal dynamics for both PTX and VBL. Tubulin polymerization induced by PTX was stable for more than 24 hr. When PTX treatment was followed by VBL, a time-and dose-dependent reversal of tubulin polymerization was observed. In contrast, rapid tubulin polymerization occurred when VBL was followed by PTX. When both agents were added simultaneously, a diminution of PTX-induced tubulin polymerization was observed with increasing doses of VBL; a maximum reduction was achieved when equal concentrations were used. Examination of the tubulin pattern by immunofluorescence in MCF-7 breast cancer cells confirmed and extended our findings. Bundle formation followed treatment with PTX. Addition of increasing concentrations of VBL prevented bundling; however, the normal cytoskeletal architecture was not restored. Cytotoxicity studies carried out using the median dose effect principles and the combination index analysis showed synergism when VBL and PTX were administered sequentially and antagonism for simultaneous administration. Our results demonstrate changes in tubulin dynamics following drug treatment and provide a rationale for combined PTX/VBL therapy after careful evaluation of the schedule of administration. (C) 1998 Wiley-Liss, Inc. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Giannakakou, Paraskevi/0000-0001-7378-262X NR 21 TC 45 Z9 48 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 5 PY 1998 VL 75 IS 1 BP 57 EP 63 DI 10.1002/(SICI)1097-0215(19980105)75:1<57::AID-IJC10>3.0.CO;2-A PG 7 WC Oncology SC Oncology GA YP060 UT WOS:000071237200010 PM 9426691 ER PT J AU Yoshiji, H Harris, SR Raso, E Gomez, DE Lindsay, CK Shibuya, M Sinha, CC Thorgeirsson, UP AF Yoshiji, H Harris, SR Raso, E Gomez, DE Lindsay, CK Shibuya, M Sinha, CC Thorgeirsson, UP TI Mammary carcinoma cells over-expressing tissue inhibitor of metalloproteinases-1 show enhanced vascular endothelial growth factor expression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; HUMAN BREAST-CANCER; TUMOR ANGIOGENESIS; TIMP-1; RECEPTOR; METASTASIS; INVASION; RNA AB The tissue inhibitor of metalloproteinases-1 (TIMP-1) has at least 2 independent functions, i.e., regulation of matrix metalloproteinases and erythroid-potentiating activity. We investigated the effects of TIMP-1 over-expression on tumor growth, using cloned lines derived from a TIMP-1-transfected rat breast carcinoma cell line. The in vitro growth rate of the TIMP-1-transfected clones was indistinguishable from that of the control. In contrast, the highest TIMP-1-producing clone (159.0 ng/ml), designated as T-H, formed 4.6-fold larger s.c. tumors than did the control after 14 days. Tumors derived from an intermediate TIMP-1-producing clone (45.4 ng/ml), designated as T-M, were 1.9-fold larger than the control. TIMP-1 over-expression was associated with increased vascular endothelial growth factor OIEGF) expression, vascularization and proliferative activity of the s.c. tumors. Similar to the rat breast carcinoma cells, transfection of TIMP-1 cDNA into the human breast carcinoma cell line MCF-7 resulted in up-regulation of VEGF, with a linear relationship between TIMP-1 and VEGF production in 9 cell clones examined. There was, however, no change in VEGF expression when the rat and human breast carcinoma cell lines were exposed to exogenous recombinant TIMP-1. Our findings suggest that over-expression of TIMP-1 confers growth advantage on breast carcinoma cells in vivo and that up-regulation of VEGF expression may play an important role in this TIMP-1 mediated, growth-stimulating effect. (C) 1998 Wiley-Liss, Inc. C1 NCI, Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Univ Tokyo, Inst Med Sci, Dept Genet, Tokyo, Japan. RP Thorgeirsson, UP (reprint author), NCI, Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci,NIH, Bldg 37,Room 2D02, Bethesda, MD 20892 USA. OI Raso, Erzsebet/0000-0002-4589-5771; Gomez, Daniel E/0000-0002-8629-0787 NR 30 TC 97 Z9 104 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 5 PY 1998 VL 75 IS 1 BP 81 EP 87 DI 10.1002/(SICI)1097-0215(19980105)75:1<81::AID-IJC13>3.3.CO;2-J PG 7 WC Oncology SC Oncology GA YP060 UT WOS:000071237200013 PM 9426694 ER PT J AU Mulberg, AE Weyler, RT Altschuler, SM Hyde, TM AF Mulberg, AE Weyler, RT Altschuler, SM Hyde, TM TI Cystic fibrosis transmembrane conductance regulator expression in human hypothalamus SO NEUROREPORT LA English DT Article DE cystic fibrosis transmembrane conductance regulator (CFTR); fertility; gonadotropin-releasing hormone (GnRH); human anterior hypothalamus; nonisotopic in situ hybridization (NISH) ID INCREASED ENERGY-EXPENDITURE; AREA POSTREMA; SOLITARY TRACT; NUCLEUS; MUTATIONS; BALANCE; WATER; CFTR AB WE have previously characterized the expression of the cystic fibrosis transmembrane conductance regulator protein (CFTR) gene, mRNA and protein in rat brain with reverse transcriptase (RT)-PCR amplification, in situ hybridization and immunocytochemistry. We now report that the CFTR mRNA is expressed in the human anterior hypothalamus, an area involved in regulation of appetite, resting energy expenditure and sexual differentiation. Expression of CFTR in neurons localized to this region may elucidate the pathogenesis of other nonpulmonary manifestations of cystic fibrosis which commonly are observed in children with CF, including congenital absence of the vas deferens. Neuron-specific expression of CFTR in brain may be involved in the regulation of homeostatic functions including reproductive function and fertility through effects on neurosecretion, i.e. GnRH release. Dysregulation of normal neuropeptide vesicle trafficking by mutant CFTR in brain my lead to alteration in physiological function. C1 Univ Penn, Dept Paediat, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA. NIMH, Clin Brain Disorders Branch, Neurosci Res Ctr, Washington, DC USA. RP Mulberg, AE (reprint author), Univ Penn, Dept Paediat, Div Gastroenterol & Nutr, 34th St & Civic Ctr Blvd Abramson 416B, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK02077] NR 23 TC 38 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 5 PY 1998 VL 9 IS 1 BP 141 EP 144 DI 10.1097/00001756-199801050-00028 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YR471 UT WOS:000071498600030 PM 9592064 ER PT J AU Patel, N Spangler, EL Greig, NH Yu, QS Ingram, DK Meyer, RC AF Patel, N Spangler, EL Greig, NH Yu, QS Ingram, DK Meyer, RC TI Phenserine, a novel acetylcholinesterase inhibitor, attenuates impaired learning of rats in a 14-unit T-maze induced by blockade of the N-methyl-D-aspartate receptor SO NEUROREPORT LA English DT Article DE acetylcholine; aging; Alzheimer's disease; glutamate; memory; neurotransmitter ID ALZHEIMERS-DISEASE; D-CYCLOSERINE; CHOLINESTERASE INHIBITOR; HEPTYL-PHYSOSTIGMINE; CHOLINERGIC SYSTEM; LONG-TERM; AGED RATS; MEMORY; PERFORMANCE; GLUTAMATE AB THE present study evaluated the interaction of the glutamatergic and acetylcholinergic systems in memory formation, with an overall emphasis on developing multi-system approaches for treating age-related cognitive decline and Alzheimer's disease. Specifically, we used a 14-unit T-maze to investigate whether phenserine (PHEN), a long-acting acetylcholinesterase inhibitor, could overcome a learning deficit in rats induced by the NMDA receptor antagonist, 3-(+/-) 2-carboxypiperzin-4-yl) propyl phosphonic acid (CPP). Prior to drug treatment, 3-month-old male Fischer-344 rats were trained to criterion (13 of 15 shock avoidances) in a straight runway. Twenty-four hours later, rats were given i.p. injections of saline (SAL), CPP (9 mg/kg) + SAL or CPP + PHEN (0.25, 0.5 or 0.75 mg/kg) and received 15 massed training trials in a 14-unit T-maze. CPP significantly increased the number of errors made in the maze relative to controls, and phenserine significantly reduced the number of errors made relative to rats receiving CPP only, with the lowest dose being the most effective. These results provide further support of phenserine's potent, cognitive-enhancing properties, and suggest that combined modulation of glutamatergic and acetylcholinergic systems may be of potential benefit in developing new pharmacotherapies for Alzheimer's disease and age-related cognitive decline. C1 Johns Hopkins Univ, NIA, Gerontol Res Ctr, Nathan W Shock Labs,Mol Physiol & Genet Sect,NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), Johns Hopkins Univ, NIA, Gerontol Res Ctr, Nathan W Shock Labs,Mol Physiol & Genet Sect,NIH, Bayview Campus,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 32 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 5 PY 1998 VL 9 IS 1 BP 171 EP 176 DI 10.1097/00001756-199801050-00035 PG 6 WC Neurosciences SC Neurosciences & Neurology GA YR471 UT WOS:000071498600037 PM 9592071 ER PT J AU Karupiah, G Sacks, TE Klinman, DM Fredrickson, TN Hartley, JW Chen, JH Morse, HC AF Karupiah, G Sacks, TE Klinman, DM Fredrickson, TN Hartley, JW Chen, JH Morse, HC TI Murine cytomegalovirus infection-induced polyclonal B cell activation is independent of CD4(+) T cells and CD40 SO VIROLOGY LA English DT Article ID VIRUS INFECTION; LYMPHOCYTES-T; MESSENGER-RNA; IMMUNE; MICE; ANTIBODIES; EXPRESSION; RESPONSES; AUTOANTIBODIES; PATHOGENESIS AB The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First, flow cytometric analysis revealed that surface expression of CD45R, IgM, and Ig kappa by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG(2a). Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4(+) T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced following infection with MCMV, but only IL-6 and IFN-gamma proteins were detectable by ELISA. In addition, the numbers of cells producing IL-B and IFN-gamma were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the absence of IFN-gamma, surface expression and serum levels of IgG(2a) were reduced while IgG(1) expression was increased. (C) 1998 Academic Press. C1 NIAID, LIP, NIH, Bethesda, MD 20892 USA. NCI, Registry Expt Canc, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Virol, Bethesda, MD USA. Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, Canberra, ACT 2601, Australia. RP Morse, HC (reprint author), NIAID, LIP, NIH, Bldg 7,Room 304,7 Ctr Dr,MSC 0760, Bethesda, MD 20892 USA. RI Karupiah, Gunasegaran/J-4707-2013; OI Morse, Herbert/0000-0002-9331-3705 NR 44 TC 30 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 1998 VL 240 IS 1 BP 12 EP 26 DI 10.1006/viro.1997.8900 PG 15 WC Virology SC Virology GA YR928 UT WOS:000071545900002 PM 9448685 ER PT J AU Ingram, DK Spangler, EL Meyer, RC London, ED AF Ingram, DK Spangler, EL Meyer, RC London, ED TI Learning in a 14-unit T-maze is impaired in rats following systemic treatment with N-w-nitro-L-arginine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE nitric oxide (NO) synthase; memory; glutamate; sodium nitroprusside; blood pressure ID LONG-TERM POTENTIATION; OXIDE SYNTHASE INHIBITOR; CENTRAL-NERVOUS-SYSTEM; MEMORY; HIPPOCAMPUS; BRAIN; NITROARGININE; LOCALIZATION; PERFORMANCE; GLUTAMATE AB We examined whether inhibition of nitric oxide synthase (NO synthase) impairs learning in male Fischer-344 rats (9 mo) in a shock-motivated 14-unit T-maze. Rats were pretrained in one-way active avoidance of foot shock to a criterion of 13/15 avoidances in a straight runway. The next day, rats received intraperitoneal (i.p.) injections of 0.9% NaCl as controls or N-w-nitro-L-arginine (N-Arg: 3.0, 4.5, or 6.0 mg/kg) to inhibit NO synthase 30 min before maze training. During 15 trials, rats were required ro negotiate each of 5 segments within 10 s to avoid footshock. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, shock frequency and duration. N-Arg treatment impaired performance on all variables in a dose-dependent manner. Specifically, only the 6 mg/kg N-Arg dose significantly increased errors compared to controls over the last 10 trials but not the first 5 trials. Controls and rats treated with 3 or 4.5 mg/kg N-Arg were retested in the maze 7-10 days following training. with half receiving N-Arg (6 mg/kg i.p.) 30 min in advance. In this retention test, maze performance was not significantly affected; thus, these results indicated that NO synthase inhibition primarily impaired acquisition without impacting upon noncognitive aspects of performance. This conclusion was further reinforced by the demonstration that 6 mg/kg N-Arg did not significantly affect sensorimotor performance in a rotarod task. When rats were treated with sodium nitroprusside, an NO donor, at 1 min, but not 30 min, prior to training, the N-Arg induced impairment (6 or 8 mg/kg i.p.) in maze learning was significantly attenuated. (C) 1998 Elsevier Science B.V. C1 NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 2 PY 1998 VL 341 IS 1 BP 1 EP 9 DI 10.1016/S0014-2999(97)01426-X PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YU560 UT WOS:000071730100001 PM 9489849 ER PT J AU Ingram, DK Spangler, EL Kametani, H Meyer, RC London, ED AF Ingram, DK Spangler, EL Kametani, H Meyer, RC London, ED TI Intracerebroventricular injection of N-omega-nitro-L-arginine in rats impairs learning in a 14-unit T-maze SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE nitric oxide (NO) synthase; sodium nitroprusside; blood pressure; memory; glutamate ID OXIDE SYNTHASE INHIBITOR; MEMORY FORMATION; TREATED RATS; CHICK AB We investigated whether intracerebroventricular (i.c,v.) infusion of the nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (N-Arg), impairs learning in male Sprague-Dawley rats (2-3 months old) in a 14-unit T-maze. Rats were pretrained in one-way active avoidance to a criterion of 13/15 avoidances of foot shock in a straight runway. The next day, rats received i.c.v, injections of either artificial cerebrospinal fluid (aCSF) as controls or N-Arg (12 mu g Or 15 mu g) 30 min before training in the 14-unit T-maze. The learning contingency was to negotiate each of 5 segments within 10 s to avoid footshock during 15 trials. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, and shock frequency and duration, Compared to controls, the number of the last 10 trials was higher in rats receiving 15 mu g N-Arg and over the last 5 trials for those given 12 mu g. Runtime, shock frequency and duration were increased in both N-Arg groups, The N Arg-induced(15 mu g i,c,v.) impairment could be attenuated when the nitric oxide donor, sodium nitroprusside (1 mg/kg), was administered intraperitoneally min prior to maze learning. In a retention test, rats were treated with either aCSF or 15 mu g N-Arg i.c.v. 30 min before being retested in the maze 7-10 d following acquisition training. Under these conditions, maze performance was not significantly affected, These results confirmed previous findings that inhibition of nitric oxide synthase impairs acquisition bur nor retention. Moreover: the N-Arg-induced learning impairment does not appear to be related to noncognitive aspects of performance. (C) 1998 Elsevier Science B.V. C1 NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 2 PY 1998 VL 341 IS 1 BP 11 EP 16 DI 10.1016/S0014-2999(97)01427-1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YU560 UT WOS:000071730100002 PM 9489850 ER PT J AU Meyer, RC Spangler, EL Patel, N London, ED Ingram, DK AF Meyer, RC Spangler, EL Patel, N London, ED Ingram, DK TI Impaired learning in rats in a 14-unit T-maze by 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, is attenuated by the nitric oxide donor, molsidomine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE glutamate; NMDA (N-methyl-D-aspartate); blood pressure; neurotransmitter; memory; Ca2+ ID LONG-TERM POTENTIATION; L-ARGININE; 7-NITRO INDAZOLE; METHYL-ESTER; L-NAME; MEMORY; MICE; HIPPOCAMPUS; STRATEGIES AB In previous experiments, it was demonstrated that systemic or central administration of the nitric oxide synthase (NO synthase) inhibitor, N-G-nitro-L-arginine (N-Arg), produced dose-dependent learning impairments in rats in a 14-unit T-maze; and that sodium nitroprusside, a NO donor, could attenuate the impairment. Since N-Arg is not specific for neuronal NO synthase and produces hypertension, it is possible that effects on the cardiovasculature may have contributed to the impaired maze performance. In the present experiment, we have investigated the maze performance of 3-4 months old male Fischer-344 rats following treatment with 7-nitroindazole, a NO synthase inhibitor that is selective for neuronal NO synthase and does not produce hypertension. In addition, we examined the effects of the NO donor, molsidomine, which is much longer acting than sodium nitroprusside. Rats were pretrained to avoid footshock in a straight runway and received training in a 14-unit T-maze 24 h later. In an initial dose-response study: rats received intraperitoneal (i.p.) injections of either 7-nitroindazole (25, 50, or 65 mg/kg) or peanut oil 30 min prior to maze training. 7-nitroindazole produced significant, dose-dependent maze acquisition deficits, with 65 mg/kg producing the greatest learning impairment. This dose of 7-nitroindazole had no significant effect on systolic blood pressure. Following the dose-response study, rats were given i.p. injections of either 7-nitroindazole (70 mg/kg) plus saline, 7-nitroindazole (70 mg/kg) plus the NO donor, molsidomine (2 or 4 mg/kg), or peanut oil plus saline as controls. Both doses of molsidomine significantly attenuated the learning deficit induced by 7-nitroindazole relative to controls. These findings represent the first evidence that impaired learning produced by inhibition of neuronal NO synthase can be overcome by systemic administration of a NO donor. (C) 1998 Elsevier Science B.V. C1 NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 34 TC 59 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 2 PY 1998 VL 341 IS 1 BP 17 EP 22 DI 10.1016/S0014-2999(97)01428-3 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YU560 UT WOS:000071730100003 PM 9489851 ER PT J AU Li, SL Termini, J Hayward, A Siddle, K Zick, Y Koval, A LeRoith, D Fujita-Yamaguchi, Y AF Li, SL Termini, J Hayward, A Siddle, K Zick, Y Koval, A LeRoith, D Fujita-Yamaguchi, Y TI The carboxyl-terminal domain of insulin-like growth factor-I receptor interacts with the insulin receptor and activates its protein tyrosine kinase SO FEBS LETTERS LA English DT Article DE insulin-like growth factor-I receptor; insulin receptor; protein tyrosine kinase; carboxyl-terminal domain; BIAcore; domain interaction ID BETA-SUBUNIT DOMAIN; HYBRID RECEPTORS; C-TERMINUS; PHOSPHORYLATION; BINDING; AUTOPHOSPHORYLATION; TRUNCATION; MECHANISM; DELETION; CELLS AB Receptors for insulin and insulin-like growth factor-I (IR and IGFIR) consisting of the alpha(2) beta(2) structure are protein tyrosine kinases (PTKs), Carboxyl-terminal (CT) domains of their beta subunits are structurally diverse while the PTK domains share the highest homology., Interactions between CT and PTK domains of IR and IGFIR were studied by means of PTK activity, fluorescence energy transfer or surface plasmon resonance using BIAcore. We present evidence that IGFIR CT directly interacts with both IGFIR and IR, Although binding to both receptors, stimulation of PTK activity only occurs with IR but not IGFIR, (C) 1998 Federation of European Biochemical Societies. C1 City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA. Univ Cambridge, Dept Clin Biochem, Cambridge, England. Weizmann Inst Sci, Dept Chem Immunol, IL-76100 Rehovot, Israel. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Fujita-Yamaguchi, Y (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, 1450 E Duarte Rd, Duarte, CA 91010 USA. FU NCI NIH HHS [CA33572]; NIDDK NIH HHS [DK34427] NR 30 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 2 PY 1998 VL 421 IS 1 BP 45 EP 49 DI 10.1016/S0014-5793(97)01523-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YU239 UT WOS:000071696200011 PM 9462837 ER PT J AU Nakahara, H Mueller, SC Nomizu, M Yamada, Y Yeh, YY Chen, WT AF Nakahara, H Mueller, SC Nomizu, M Yamada, Y Yeh, YY Chen, WT TI Activation of beta 1 integrin signaling stimulates tyrosine phosphorylation of p190(RhoGAP) and membrane-protrusive activities at invadopodia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX; CELL-ADHESION; TRANSFORMED-CELLS; IN-VITRO; PROTEINS; PEPTIDES; INVASION; KINASE; SITES; P190 AB The ligation of available alpha 6 beta 1 integrin in adherent LOX melanoma cells by laminin G peptides and integrin stimulatory antibodies induced cell invasiveness, independent of adhesion activity of integrins that were prebound to extracellular matrix (Nakahara, H, Nomizu, M., Akiyama, S. K,, Yamada, Y., Yeh, Y., and Chen, W,-T, (1996) J. Biol. Chem. 271, 27221-27224). Here, we show that this induced invasion involves an increase in tyrosine phosphorylation of a 190-kDa GTPase-activating protein for Rho family members (p190(RhoGAP); p190) and membrane-protrusive activities at invadopodia, This tyrosine phosphorylation does not occur when the adherent cells are treated with non-activating antibody against pi integrin, control laminin peptides, or tyrosine kinase inhibitors genistein and herbimycin A, Although p190 and F-actin co-distribute in all cell cortex extensions, tyrosine-phosphorylated proteins including p190 appear to associate with F-actin specifically in invadopodia. In addition, the localized matrix degradation and membrane-protrusive activities were blocked by treatment of LOX cells with tyrosine kinase inhibitors as well as microinjection of antibodies directed against p190 but not by non-perturbing antibodies or control buffers, We suggest that activation of the alpha 6 beta 1 integrin signaling regulates the tyrosine phosphorylation state of p190 which in turn connects downstream signaling pathways through Rho family GTPases to actin cytoskeleton in invadopodia, thus promoting membrane-protrusive and degradative activities necessary for cell invasion. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WT (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, TRB E415,3970 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA-61273, R01 CA-39077]; NHLBI NIH HHS [HL-33711] NR 32 TC 137 Z9 139 U1 1 U2 5 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 JAN 2 PY 1998 VL 273 IS 1 BP 9 EP 12 DI 10.1074/jbc.273.1.9 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600003 PM 9417037 ER PT J AU Choi, SG Yi, Y Kim, YS Kato, M Chang, J Chung, HW Hahm, KB Yang, HK Rhee, HH Bang, YJ Kim, SJ AF Choi, SG Yi, Y Kim, YS Kato, M Chang, J Chung, HW Hahm, KB Yang, HK Rhee, HH Bang, YJ Kim, SJ TI A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; MICROSATELLITE INSTABILITY; MOLECULAR-CLONING; DOMAIN PROTEIN; CANCER CELLS; GENE; FAMILY; PROMOTER; MEMBER; ELEMENTS AB A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system, The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain, Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter, A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay, Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region, Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Canc Res Ctr, Seoul, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Rm B1106, Bethesda, MD 20892 USA. RI Yang, Han-Kwang/J-2767-2012; Bang, Yung Jue/J-2759-2012 NR 33 TC 99 Z9 101 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 JAN 2 PY 1998 VL 273 IS 1 BP 110 EP 117 DI 10.1074/jbc.273.1.110 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600020 PM 9417054 ER PT J AU Horuk, R Hesselgesser, J Zhou, YQ Faulds, D Halks-Miller, M Harvey, S Taub, D Samson, M Parmentier, M Rucker, J Doranz, BJ Doms, RW AF Horuk, R Hesselgesser, J Zhou, YQ Faulds, D Halks-Miller, M Harvey, S Taub, D Samson, M Parmentier, M Rucker, J Doranz, BJ Doms, RW TI The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; T-LYMPHOCYTES; RECEPTOR; GENE; CELLS; INDIVIDUALS; PROGRESSION; EXPRESSION; CORECEPTOR; RESISTANCE AB Using a chemokine receptor model based on known receptor sequences, we identified several members of the seven transmembrane domain G-protein superfamily as potential chemokine receptors, The orphan receptor ChemR1, which has recently been shown to be a receptor for the CC chemokine I-309, scored very high in our model, We have confirmed that I-309, but not a number of other chemokines, can induce a transient Ca2+ flux in cells expressing CCR8, In addition, the human erythroleukemic cell line K562 responded chemotactically in a dose-responsive manner to this chemokine, Since several chemokine receptors have been shown to be required as coreceptors for HIV-1 infection, we asked whether human immunodeficiency virus type 1 (HIV-1) could efficiently utilize CCR8, Here we show that the CCR8 receptor can serve as a coreceptor for diverse T-cell tropic, dual-tropic, and macrophage-tropic HIV-1 strains and that I-309 was a potent inhibitor of HIV-1 envelope-mediated cell-cell fusion and virus infection, Furthermore, we show by flow cytometry and immunohistochemistry that antibodies generated against the CCR8 receptor amino-terminal peptide cross-reacted with U-87 MG cells stably expressing CCR8, THP-1 cells, HL-60 cells, and human monocytes, a target cell for HIV-1 infectivity in vivo. C1 Berlex Biosci, Dept Immunol, Richmond, CA 94804 USA. Berlex Biosci, Dept Pharmacol, Richmond, CA 94804 USA. Berlex Biosci, Dept Cell Biol, Richmond, CA 94804 USA. NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Free Univ Brussels, IRIBHN, B-1070 Brussels, Belgium. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Horuk, R (reprint author), Berlex Biosci, Dept Immunol, 15049 San Pablo Ave, Richmond, CA 94804 USA. RI Samson, Michel/F-8356-2013 FU NIAID NIH HHS [AI-40880, AI-38225] NR 38 TC 139 Z9 141 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 JAN 2 PY 1998 VL 273 IS 1 BP 386 EP 391 DI 10.1074/jbc.273.1.386 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600059 PM 9417093 ER PT J AU Jones, PLS Korte, T Blumenthal, R AF Jones, PLS Korte, T Blumenthal, R TI Conformational changes in cell surface HIV-1 envelope glycoproteins are triggered by cooperation between cell surface CD4 and co-receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUSION; BINDING; ENTRY; GP120; HEMAGGLUTININ; MEMBRANES; COFACTOR; KINETICS; PROTEINS; LINES AB We have continuously measured CD4-induced conformational changes of cell surface expressed human immunodeficiency virus type-1 envelope glycoprotein gp120-gp41 irt situ using 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid, a fluorescent probe that binds to hydrophobic groups. CD4-expressing human T cell lines induced significant and rapid conformational changes (<1 min delay) in gp120-gp41 from T cell-tropic strains, and little conformational changes in gp120-gp41 from macrophage-tropic strains, with equivalent levels of envelope expression. Conversely, CD4-expressing human macrophages induced significant and rapid conformational changes in gp120-gp41 from macrophage-tropic strains, and little conformational changes in gp120-gp41 from T cell-tropic strains. Thus, the conformational changes undergone by gp120-gp41, which lead to membrane fusion, are highly cooperative and require both receptor and co-receptor. We used a dye transfer assay to show that neither membrane lipid fusion or fusion pore formation can occur with host cells having different tropism from the envelope. C1 NCI, Frederick Canc Res & Dev Ctr, Sect Membrane Struct & Funct, Lab Expt & Computat Biol,Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sect Membrane Struct & Funct, Lab Expt & Computat Biol,Div Basic Sci,NIH, Bldg 469,Rm 213,POB B,Miller Dr, Frederick, MD 21702 USA. NR 31 TC 166 Z9 170 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 JAN 2 PY 1998 VL 273 IS 1 BP 404 EP 409 DI 10.1074/jbc.273.1.404 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600062 PM 9417096 ER PT J AU Dana, R Leto, TL Malech, HL Levy, R AF Dana, R Leto, TL Malech, HL Levy, R TI Essential requirement of cytosolic phospholipase A(2) for activation of the phagocyte NADPH oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LEUKEMIA CELL-LINE; HUMAN NEUTROPHILS; ARACHIDONIC-ACID; PROTEIN-KINASE; HL-60 CELLS; CYTOPLASMIC PHOSPHOLIPASE-A(2); SUPEROXIDE GENERATION; RESPIRATORY BURST; EXPRESSION AB Arachidonic acid (AA) can trigger activation of the phagocyte NADPH oxidase in a cell-free assay. However, a role for AA in activation of the oxidase in intact cells has not been established, nor has the AA generating enzyme critical to this process been identified, The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A(2) (cPLA(2)) antisense mRNA and stable clones were selected that lack detectable cPLA(2). cPLA(2)-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid or 1,25-dihydroxyvitamin D-3, indicating that cPLA(2) is not involved in the differentiation process. Neither cPLA(2) nor stimulated [H-3]AA release were detectable in differentiated cPLA(2)-deficient PLB-985 cells, demonstrating that cPLA(2) is the major type of PLA(2) activated in phagocytic-like cells. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA(2)-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but the addition of exogenous AA fully restores oxidase activity. This establishes an essential requirement of cPLA(2)-generated AA for activation of phagocyte NADPH oxidase. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Infect Dis Lab, Dept Clin Biochem, IL-84105 Beer Sheva, Israel. Soroka Med Ctr, IL-84105 Beer Sheva, Israel. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Levy, R (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Infect Dis Lab, Dept Clin Biochem, IL-84105 Beer Sheva, Israel. NR 44 TC 164 Z9 169 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 JAN 2 PY 1998 VL 273 IS 1 BP 441 EP 445 DI 10.1074/jbc.273.1.441 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600067 PM 9417101 ER PT J AU Lai, WS Thompson, MJ Blackshear, PJ AF Lai, WS Thompson, MJ Blackshear, PJ TI Characteristics of the intron involvement in the mitogen-induced expression of Zfp-36 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE-C; FINGER TRANSCRIPTION FACTOR; RECEPTOR GENE-EXPRESSION; BOX-BINDING PROTEINS; DNA-BINDING; SYNERGISTIC ACTIVATION; NUCLEAR-PROTEIN; MAMMALIAN-CELLS; SV40 ENHANCER AB Zfp-36, the gene encoding the putative zinc finger protein tristetraprolin (TTP), is rapidly induced in fibro blasts by a variety of growth factors. Recent gene knockout experiments have shown that TTP-deficient mice developed arthritis, cachexia, and autoimmunity, all apparently mediated by an excess of tumor necrosis factor cu, We recently showed that full serum inducibility of Zfp-36 requires elements in the promoter; in addition, removal of the single intron strikingly inhibited serum-induced TTP expression, We show here that replacement of the intron with unrelated sequences, or removal of 95% of the intron but retention of the splice sites, each resulted in the maintenance of approximately 45 and 19%, respectively, of full serum-induced expression. In addition, deletion of intron sequences base pairs 601-655 decreased the serum-induced expression of TTP by 65%. Sequence base pairs 618-626 bound specifically to the transcription factor Spl; mutation of this binding motif decreased TTP expression by 70%, suggesting that Spl binding to this motif contributes to serum induction of Zfp-36. We conclude that full serum-induced expression of Zfp-36 depends on the activation of conventional promoter elements as well as elements in the single intron, and that the presence per se of the intron in its natural location also contributes significantly to the regulated expression of this gene. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst Labs, Sect Diabet & Metab,Div Endocrinol Metab & Nutr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, MD-A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIDDK NIH HHS [T32-DK-07012, K11-DK02227-02] NR 62 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 1998 VL 273 IS 1 BP 506 EP 517 DI 10.1074/jbc.273.1.506 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600075 PM 9417109 ER PT J AU Hilliard, JJ Maurizi, MR Simon, LD AF Hilliard, JJ Maurizi, MR Simon, LD TI Isolation and characterization of the phage T4 PinA protein inhibitor of the ATP-dependent Lon protease of Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLP PROTEASE; BACTERIOPHAGE-T4 GENE; LAMBDA-N; ION GENE; LA; DEGRADATION; PROTEOLYSIS; COMPONENT; SEQUENCE; QUANTITATION AB The bacteriophage T4 PinA protein, expression of which leads to inhibition of protein degradation in Escherichia coli cells, has been purified from cells carrying multiple copies of the pinA gene. PinA is a heat-stable protein with a subunit M-r of 18,800 and an isoelectric point of 4.6, Under nondenaturing conditions on a gel filtration column, PinA migrated in two peaks corresponding to a dimer and a tetramer, Purified Pink inhibited ATP-dependent protein degradation by Lon protease in vitro; it did not inhibit the activity of other E. coli ATP-dependent proteases, ClpAP or ClpYQ, Furthermore, PinA did not inhibit ATP-independent proteolysis in E. coli cell extracts, PinA binds with high affinity to Lon protease (K-d similar to 10 nM for dimer binding), and a complex with similar to 1 dimer of PinA per tetramer of Lon protease could be isolated by gel filtration, Lon activity was partially restored upon dilution of the PinA-Lon complex to subnanomolar concentrations, indicating that inhibition was reversible and that PinA did not covalently modify Lon protease, PinA was not cleaved by Lon protease, and heating the Lon-PinA complex at 65 degrees C denatured Lon protease and released active Pink The properties of PinA in vitro suggest that PinA inhibits protein degradation in vivo by forming a tight, reversible complex with Lon protease. C1 Rutgers State Univ, Waksman Inst, Piscataway, NJ 08855 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Simon, LD (reprint author), Rutgers State Univ, Waksman Inst, Piscataway, NJ 08855 USA. NR 41 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 1998 VL 273 IS 1 BP 518 EP 523 DI 10.1074/jbc.273.1.518 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600076 PM 9417110 ER PT J AU Hilliard, JJ Simon, LD Van Melderen, L Maurizi, MR AF Hilliard, JJ Simon, LD Van Melderen, L Maurizi, MR TI PinA inhibits ATP hydrolysis and energy-dependent protein degradation by Lon protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SUBSTRATES ACTIVATE; LA; PURIFICATION; PROTEOLYSIS; PEPTIDES; BINDING; GENE AB The bacteriophage T4 PinA protein inhibited degradation of [H-3]alpha-methyl casein by purified Lon protease from Escherichia coli, but inhibition was noncompetitive with respect to casein, PinA did not inhibit cleavage of the fluorogenic peptide, N-glutaryl-alanylalanylphenylalanyl-3-methoxynaphthylamide and, moreover, did not block the ability of protein substrates, such as casein, to activate cleavage of fluorogenic peptides by Lon, Thus, PinA does not block the proteolytic active site or the allosteric protein-binding site on Lon, Inhibition of basal ATPase activity was variable (50-90%), whereas inhibition of protein-activated ATPase activity was usually 80-95%, Inhibition was noncompetitive with respect to ATP, PinA did not block activation of peptide cleavage by nonhydrolyzable analogs of ATP, These data suggest that PinA does not bind at the ATPase active site of Lon and does not interfere with nucleotide binding to the enzyme, PinA inhibited cleavage of the 72-amino acid protein, CcdA, degradation of which requires ATP hydrolysis, but did not inhibit cleavage of the carboxyl-terminal 41-amino acid fragment of CcdA, degradation of which does not require ATP hydrolysis, PinA thus appears to interact at a novel regulatory or enzymatic site involved in the coupling between ATP hydrolysis and proteolysis, possibly blocking the protein unfolding or remodeling step essential for degradation of high molecular weight protein substrates by Lon. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Waksman Inst, Piscataway, NJ 08855 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1B07, Bethesda, MD 20892 USA. NR 20 TC 16 Z9 17 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 JAN 2 PY 1998 VL 273 IS 1 BP 524 EP 527 DI 10.1074/jbc.273.1.524 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600077 PM 9417111 ER PT J AU Butscher, WG Powers, C Olive, M Vinson, C Gardner, K AF Butscher, WG Powers, C Olive, M Vinson, C Gardner, K TI Coordinate transactivation of the interleukin-2 CD28 response element by c-Rel and ATF-1/CREB2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL ACTIVATION; NF-KAPPA-B; ACCESSORY MOLECULE CD28; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; PROTEIN-KINASE; MULTIORGAN INFLAMMATION; SIGNAL-TRANSDUCTION; GENE-TRANSCRIPTION; LYMPHOCYTES-T AB The interleukin-a CD28 response element (CD28RE) acts as a composite enhancer, in conjunction with a 3'-12-O-tetradecanoylphorbol-13-acetate response element (TRE)-like element, to confer CD28 receptor-dependent inducibility to the interleukin-2 promoter in T-cells, When inserted as a single copy upstream of a basal promoter, this composite enhancer, termed the CD28RE-TRE, is both highly active and CD28-inducible in transactivation assays, A multicomponent nuclear protein complex that binds the CD28RE-TRE was isolated by DNA affinity chromatography from nuclear extracts of mitogen- and CD28 receptor-costimulated hu. man T-cells. Immunological and biochemical analyses of this complex reveal the presence of c-Rel, ATF-1, and CREB2 as major DNA-binding components, Coexpression of c-Rel in combination with ATF-1, CREB2, or ATF-1/CREB2 leads to synergistic transactivation of a CD28RE-TRE reporter plasmid in quiescent Jurkat T-cells, Furthermore, CD28-dependent transactivation of the CD28RE-TRE is specifically inhibited by cAMP response element-binding protein (CREB) dominant-negative expression vectors, Moreover, mutant promoter constructs in which the internal 5'-CD28RE and 3'-TRE-like sequences have been topologically positioned 180 degrees out of phase with one another show loss of mitogen-and CD28-dependent inducibility. Finally, the addition of the CREB binding transcriptional coactivator p300 leads to a dramatic CREB-dependent increase in both mitogen-and CD28-mediated transactivation of the CD28RE-TRE. These findings demonstrate that full physiological responsiveness to CD28 receptor stimulation in T-cells is dependent on topologically linked sequences within the CD28RE-TRE composite enhancer and provide strong support of a direct role for the CREB family of transcription factors and p300/CREB-binding protein coactivator proteins in cytokine gene induction during T-cell activation. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Gardner, K (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2N212, Bethesda, MD 20892 USA. RI Powers, Ciaran/E-3890-2011 NR 65 TC 79 Z9 83 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 JAN 2 PY 1998 VL 273 IS 1 BP 552 EP 560 DI 10.1074/jbc.273.1.552 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600081 PM 9417115 ER PT J AU Cawley, NX Olsen, V Zhang, CF Chen, HC Tan, M Loh, YP AF Cawley, NX Olsen, V Zhang, CF Chen, HC Tan, M Loh, YP TI Activation and processing of non-anchored yapsin 1 (Yap3p) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST ASPARTIC PROTEASE-3; SACCHAROMYCES-CEREVISIAE; PROTEINASE-A; SUBSTRATE-SPECIFICITY; PROCATHEPSIN-D; ALPHA-FACTOR; IN-VIVO; GENE; MATURATION; SECRETION AB A C-terminally truncated form of yapsin 1 (yeast aspartic protease 3), the first member of the novel subclass of aspartic proteases with specificity for basic residues (designated the Yapsins), was overexpressed and purified to apparent homogeneity, yielding similar to 1 mu g of yapsin 1/g of wet yeast, N-terminal amino acid analysis of the purified protein confirmed that the propeptide was absent and that the mature enzyme began at Ala(68). The mature enzyme was shown to be composed of approximately equimolar amounts of two subunits, designated alpha and beta, that were associated to each other by a disulfide bond. C-terminally truncated proyapsin 1 was also expressed in the baculovirus/Sf9 insect cell expression system and secreted as a zymogen that could be activated upon incubation at an acidic pH with an optimum at similar to 4.0, When expressed without its pro-region, it was localized intracellularly and lacked activity, indicating that the pro-region was required for the correct folding of the enzyme, The activation of proyapsin 1 in vitro exhibited linear kinetics and generated an intermediate form of yapsin 1 or pseudo-yapsin 1. C1 NICHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Cawley, NX (reprint author), NICHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A38, Bethesda, MD 20892 USA. NR 43 TC 25 Z9 26 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 JAN 2 PY 1998 VL 273 IS 1 BP 584 EP 591 DI 10.1074/jbc.273.1.584 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600085 PM 9417119 ER PT J AU Paolini, M Pozzetti, L Sapone, A Cantelli-Forti, G AF Paolini, M Pozzetti, L Sapone, A Cantelli-Forti, G TI Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases SO LIFE SCIENCES LA English DT Article DE licorice; hepatic microsomes; CYP 3A; testosterone hydroxylase; enzymatic induction ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HEALTHY-VOLUNTEERS; INDUCTION; PROTEINS; ACID; RAT; SEX AB This study is aimed to investigate the effect of the prolonged intake of conspicuous amounts of licorice (LE), or its natural constituent glycyrrhizin (G) on murine liver CYP-catalyzed drug metabolism. For this purpose the modulation of the regio-and stereo-selective hydroxylation of testosterone, together with the use of highly specific substrates as probes for different CYP isoforms such as ethoxyresorufin (CYP1A1), methoxyresorufin (1A2), pentoxyresorufin (2B1), p-nitrophenol (2E1) and aminopyrine (3A), were investigated. Daily doses of licorice root extract (3,138 or 6,276 mg/kg b.w. per os), or G (240 or 480 mg/kg b.w. per os), were administered to different groups of Swiss Albino CD1 mice of both sexes for 1, 4 or 10 consecutive days. While a single LE or G dose was unable to affect the multienzymatic CYP-system, using both schedules of repeated treatment, either LE or G were able to significantly induce hepatic CYP3A-and, to a lesser extent, 2B1-and 1A2-dependent microsomal monooxygenase activities, as well as 6 beta-(mainly associated to CYP3A), 2 alpha-, 6 alpha-(CYP2A1, 2B1), 7 alpha-, 16 alpha-(CYP2B9) and 16 beta-testosterone hydroxylase (TH) activities in male and female mice. Data on CYP3A modulation, the major isoform present in human liver, was confirmed by using Western immunoblotting with anti-CYP3A1/2 rabbit polyclonal antibodies raised against purified rat CYP3A. Northern blotting analysis using CYP3A cDNA biotinylated probe showed that the expression of such isozyme is regulated at the mRNA level. These results suggest that the induction of cytochrome P450-dependent activities by the prolonged intake of high LE or G doses, may result in accelerated metabolism of coadministered drugs with important implications for their disposition. The adverse effects associated with CYP changes such as toxicity/cotoxicity and comutagenicity may also have clinical consequences. C1 Univ Bologna, Dept Pharmacol, Biochem Toxicol Unit, I-40126 Bologna, Italy. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77550 USA. RP Paolini, M (reprint author), Univ Bologna, Dept Pharmacol, Biochem Toxicol Unit, Via Imerio 48, I-40126 Bologna, Italy. EM paolini@biocfarm.unibo.it RI Sapone, Andrea/E-6704-2013; OI Sapone, Andrea/0000-0001-8496-6977; paolini, moreno/0000-0002-2338-8859 NR 39 TC 44 Z9 66 U1 0 U2 1 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 JAN 2 PY 1998 VL 62 IS 6 BP 571 EP 582 DI 10.1016/S0024-3205(97)01154-5 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA YQ296 UT WOS:000071371100011 PM 9464470 ER PT J AU Chesebro, B AF Chesebro, B TI Prion diseases - BSE and prions: Uncertainties about the agent SO SCIENCE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; TRANSGENIC MICE; NEURODEGENERATION; PROTEIN C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 14 TC 140 Z9 145 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 2 PY 1998 VL 279 IS 5347 BP 42 EP 43 DI 10.1126/science.279.5347.42 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YP866 UT WOS:000071323900032 PM 9441410 ER PT J AU Braun, AR Balkin, TJ Wesensten, NJ Gwadry, F Carson, RE Varga, M Baldwin, P Belenky, G Herscovitch, P AF Braun, AR Balkin, TJ Wesensten, NJ Gwadry, F Carson, RE Varga, M Baldwin, P Belenky, G Herscovitch, P TI Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep SO SCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN BRAIN; REM-SLEEP; CORTEX; IMAGERY; WAVES; PET AB Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the ventral processing stream, and an unexpected attenuation of activity in the primary visual cortex; increases in regional cerebral blood flow in extrastriate areas were significantly correlated with decreases in the striate cortex. Extrastriate activity was also associated with concomitant activation of limbic and paralimbic regions, but with a marked reduction of activity in frontal association areas including lateral orbital and dorsolateral prefrontal cortices. This pattern suggests a model for brain mechanisms subserving REM sleep where visual association cortices and their paralimbic projections may operate as a closed system dissociated from the regions at either end of the visual hierarchy that mediate interactions with the external world. C1 NIDOCD, Voice Speech & Language Branch, Language Sect, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Neurobiol & Behav, Div Neuropsychiat, Washington, DC 20307 USA. NIH, Ctr Clin, PET Imaging Sect, Bethesda, MD 20892 USA. RP Braun, AR (reprint author), NIDOCD, Voice Speech & Language Branch, Language Sect, NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 39 TC 272 Z9 278 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 2 PY 1998 VL 279 IS 5347 BP 91 EP 95 DI 10.1126/science.279.5347.91 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YP866 UT WOS:000071323900047 PM 9417032 ER PT J AU Shisler, JL Senkevich, TG Berry, MJ Moss, B AF Shisler, JL Senkevich, TG Berry, MJ Moss, B TI Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus SO SCIENCE LA English DT Article ID MOLLUSCUM CONTAGIOSUM VIRUS; VACCINIA VIRUS; SELENOCYSTEINE INCORPORATION; GENE-EXPRESSION; MAMMALIAN-CELLS; SEQUENCE; EUKARYOTES; APOPTOSIS; BIOLOGY; ELEMENT AB Selenium, an essential trace element, is a component of prokaryotic and eukaryotic antioxidant proteins, A candidate selenoprotein homologous to glutathione peroxidase was deduced from the sequence of molluscum contagiosum, a poxvirus that causes persistent skin neoplasms in children and acquired immunodeficiency syndrome (AIDS) patients. Selenium was incorporated into this protein during biosynthesis, and a characteristic stem-loop structure near the end of the messenger RNA was required for alternative selenocysteine decoding of a potential UGA stop codon within the open reading frame. The selenoprotein protected human keratinocytes against cytotoxic effects of ultraviolet irradiation and hydrogen peroxide, providing a mechanism for a virus to defend itself against environmental stress. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Inst Med, Boston, MA 02115 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK47320] NR 30 TC 105 Z9 108 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 2 PY 1998 VL 279 IS 5347 BP 102 EP 105 DI 10.1126/science.279.5347.102 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YP866 UT WOS:000071323900050 PM 9417017 ER PT B AU Caspi, RR Sun, B Sun, SH Rizzo, LV Chan, CC Wiggert, B AF Caspi, RR Sun, B Sun, SH Rizzo, LV Chan, CC Wiggert, B BE Talwar, GP Nath, I Ganguly, NK Rao, KVS TI Experimental autoimmune uveitis is associated with conversion from an early Th0-like response to a Th1-like response in susceptible, but not in resistant mice SO 10TH INTERNATIONAL CONGRESS ON IMMUNOLOGY, VOLS 1 AND 2 LA English DT Proceedings Paper CT 10th International Congress of Immunology CY NOV 01-06, 1998 CL NEW DELHI, INDIA AB Susceptible strains of rodents immunized for induction of experimental autoimmune uveitis (EAU) with the uveitogenic protein IRBP exhibit a dominant type 1 response at the time of disease expression. Here we use EAU-susceptible B10.A and EAU- resistant BALB/c mice to analyze evolution the cytokine and antibody responses to IRBP during the development of EAU. Both strains exhibited an IgG1-dominated antibody response on day 7, which converted by day 14 to an IgG2a-dominated response in B10.A. but remained IgG1 dominated in BALB/c. Antigen-specific production of type 1 cytokines increased from day 7 to day 14 in B10.A, whereas production of type 2 cytokines decreased. BALB/c showed the opposite pattern. with a decrease in type 1 and an increase in type 2 cytokines. All B10.A mice developed EAU by day 14, whereas BALB/c mice remained disease-free even on day 21. Thus, both susceptible and resistant mice initially exhibit a type 0 response to IRBP. Susceptibility to EAU is associated with conversion to a type 1 response, whereas resistance is associated with an increased polarization towards a type 1 response, whereas resistance is associated with an increased polarization towards a type 2 response. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-1101-1 PY 1998 BP 291 EP 299 PG 9 WC Immunology SC Immunology GA BM18S UT WOS:000077938500049 ER PT B AU Fauci, AS AF Fauci, AS BE Girard, M Dodet, B TI Host factors in the pathogenesis of HIV disease SO 11E COLLOQUE DES CENT GARDES: RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 11th Cent Gardes Symposium CY OCT 27-29, 1997 CL MARNES COQUETTE, FRANCE C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 31,Room 7A-03,31 Ctr DR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-022-6 PY 1998 BP 227 EP 232 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BK85G UT WOS:000073664200031 ER PT B AU Lifson, JD Nowak, MA Lloyd, AL Hirsch, VM AF Lifson, JD Nowak, MA Lloyd, AL Hirsch, VM BE Girard, M Dodet, B TI Clues to primate lentiviral pathogenesis from the study of SIV viral dynamics SO 11E COLLOQUE DES CENT GARDES: RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 11th Cent Gardes Symposium CY OCT 27-29, 1997 CL MARNES COQUETTE, FRANCE C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Lab Retroviral Pathogenesis,AIDS Vaccine Program, Frederick, MD 21702 USA. RP Lifson, JD (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Lab Retroviral Pathogenesis,AIDS Vaccine Program, POB B, Frederick, MD 21702 USA. RI Lloyd, Alun/H-4944-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-022-6 PY 1998 BP 245 EP 252 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BK85G UT WOS:000073664200033 ER PT B AU Chun, TW Stuyver, L Fauci, AS AF Chun, TW Stuyver, L Fauci, AS BE Girard, M Dodet, B TI Replication-competent HIV-1 persists in latently infected resting CD4(+) T cells during highly active antiretroviral therapy SO 11E COLLOQUE DES CENT GARDES: RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 11th Cent Gardes Symposium CY OCT 27-29, 1997 CL MARNES COQUETTE, FRANCE C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A32,10 Ctr Dr,MSC 1576, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-022-6 PY 1998 BP 309 EP 314 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BK85G UT WOS:000073664200044 ER PT B AU Hauser, SE Browne, AC Thoma, GR McCray, AT AF Hauser, SE Browne, AC Thoma, GR McCray, AT GP IEEE TI Lexicon assistance reduces manual verification of OCR output SO 11TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 11th IEEE Symposium on Computer-Based Medical Systems CY JUN 12-14, 1998 CL LUBBOCK, TX SP IEEE Comp Soc, IEEE Comp Soc Tech Comm Computat Med, IEEE S Plains Sect-Reg V, Int Soc Optical Engn (SPIE), TX Tech Univ Health Sci Ctr, Dept Radiol AB An OCR system chosen for its high recognition rate and low percent of false positives also assigns low confidence values to many characters that are actually correct. Human operators must verify all words containing low confidence characters. We describe the creation of a lexicon optimized for automatically selectively resetting confidence values to high, thus reducing operator verification time. Two word lists, OCR Correct and OCR Incorrect, were extracted from files already processed and verified and became the standard for comparing candidate lexicons. A lexicon was selected from several candidate word lists maintained by the National Library of Medicine (NLM). In operation for about six months, lexicon assisted verification has been reducing the number of words requiring operator verification by over 50%. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Hauser, SE (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-8186-8563-8 PY 1998 BP 90 EP 95 DI 10.1109/CBMS.1998.701267 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BL28S UT WOS:000074993900016 ER PT B AU Thoma, GR AF Thoma, GR GP IEEE TI Automating data entry for biomedical databases SO 11TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 11th IEEE Symposium on Computer-Based Medical Systems CY JUN 12-14, 1998 CL LUBBOCK, TX SP IEEE Comp Soc, IEEE Comp Soc Tech Comm Computat Med, IEEE S Plains Sect-Reg V, Int Soc Optical Engn (SPIE), TX Tech Univ Health Sci Ctr, Dept Radiol AB Data entry from paper-based literature, e.g., medical journals, into databases has traditionally been manual and labor-intensive. As the journal sets grow in number and the number of entries correspondingly increase, the traditional approach has proven to be burdensome. More automated approaches relying on scanning, optical character recognition (OCR), image segmentation, biomedical lexicons and image processing have to be introduced. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Thoma, GR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-8186-8563-8 PY 1998 BP 200 EP 201 DI 10.1109/CBMS.1998.701348 PG 2 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BL28S UT WOS:000074993900033 ER PT B AU Long, LR Thoma, GR Goh, GH Neve, L AF Long, LR Thoma, GR Goh, GH Neve, L GP IEEE TI Multimedia biomedical database tools for digital x-rays SO 11TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 11th IEEE Symposium on Computer-Based Medical Systems CY JUN 12-14, 1998 CL LUBBOCK, TX SP IEEE Comp Soc, IEEE Comp Soc Tech Comm Computat Med, IEEE S Plains Sect-Reg V, Int Soc Optical Engn (SPIE), TX Tech Univ Health Sci Ctr, Dept Radiol AB In this paper we describe two projects at the Lister Hill National Center for Biomedical Communications of the the National Library of Medicine. The first project is a digital atlas for the interpretation of osteoarthritic conditions in the cervical and lumbar spines, using methodology developed by the National Institute of Arthritis and Musculoskeletal aid Skin Diseases (NIAMS). The goal of the the atlas project is to provide a standard digital reference tool for interpretation of this class of x-ray images, and a computer-based tool for medical education in radiology and rheumatology. The second project is a system for dissemination of,national health survey data, including both text and digitized images, in a platform-independent manner using the World Wide Web. The goal of this second project, called WebMIRS, is to provide wide access to important sets of national health survey data to the epidemiological community, to rheumatologist and radiologist researchers interested in the image data, and to medical educators. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-8186-8563-8 PY 1998 BP 202 EP 207 DI 10.1109/CBMS.1998.701349 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BL28S UT WOS:000074993900034 ER PT B AU Percy, C Ries, L AF Percy, C Ries, L BE Moraes, M Brentani, R Bevilacqua, R TI Incidence and mortality from HIV disease and cancer in young men in the United States, 1987-1994 SO 17TH INTERNATIONAL CANCER CONGRESS, VOL 1 AND 2 LA English DT Proceedings Paper CT 17th International Cancer Congress of the International-Union-Against-Cancer CY AUG 24-28, 1998 CL RIO JANEIRO, BRAZIL SP Int Union Against Canc, FAF, INCA C1 Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Percy, C (reprint author), Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0824-X PY 1998 BP 377 EP 380 PG 4 WC Oncology; Medicine, General & Internal; Pathology SC Oncology; General & Internal Medicine; Pathology GA BL70X UT WOS:000076408700069 ER PT B AU Cheson, BC AF Cheson, BC BE Moraes, M Brentani, R Bevilacqua, R TI Current approaches to therapy for indolent non-Hodgkin's lymphomas SO 17TH INTERNATIONAL CANCER CONGRESS, VOL 1 AND 2 LA English DT Proceedings Paper CT 17th International Cancer Congress of the International-Union-Against-Cancer CY AUG 24-28, 1998 CL RIO JANEIRO, BRAZIL SP Int Union Against Canc, FAF, INCA C1 Natl Canc Inst, Bethesda, MD 20892 USA. RP Cheson, BC (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0824-X PY 1998 BP 1357 EP 1362 PG 6 WC Oncology; Medicine, General & Internal; Pathology SC Oncology; General & Internal Medicine; Pathology GA BL70X UT WOS:000076408700259 ER PT B AU Riddell, C Barker, WC Bacharach, SL AF Riddell, C Barker, WC Bacharach, SL BE Nalcioglu, O TI Limited sinogram completion for transmission SPECT imaging SO 1997 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1 & 2 LA English DT Proceedings Paper CT 1997 IEEE Nuclear Science Symposium and Medical Imaging Conference CY NOV 09-15, 1997 CL ALBUQUERQUE, NM SP IEEE AB Truncation artifacts can occur in simultaneous emission transmission SPECT imaging even with parallel geometry, especially when the acquisition geometry is optimized for emission at the expense of the transmission data. We hypothesized that the addition of only a few projections sampling the truncated area after a bed/camera shift could permit a significant improvement in image quality with only a small increase in imaging time. Because in parallel geometry, such a shift results in column shifts of the sinogram at each angle, it is straightforward to merge any additional projection into the original sinogram, thereby partially completing it. The resulting data still require the use of an iterative reconstruction algorithm. Improvements due to partial completion are studied in the case of a 90 degree dual-headed camera: Results on simulated and true data show that only 4 completed projections can lead to a better recovery of the truncated area than does the a priori knowledge of the body contour. C1 NIH, Bethesda, MD 20892 USA. RP Riddell, C (reprint author), NIH, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-4259-3 PY 1998 BP 1131 EP 1134 PG 4 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Radiology, Nuclear Medicine & Medical Imaging SC Instruments & Instrumentation; Nuclear Science & Technology; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BL13T UT WOS:000074401900245 ER PT S AU Ritter, T Shung, KK Geng, X Wang, H Shrout, TR AF Ritter, T Shung, KK Geng, X Wang, H Shrout, TR BE Schneider, SC Levy, M McAvoy, BR TI 30 MHz medical imaging arrays incorporating 2-2 composites SO 1998 IEEE ULTRASONICS SYMPOSIUM - PROCEEDINGS, VOLS 1 AND 2 SE Ultrasonics Symposium LA English DT Proceedings Paper CT 1998 IEEE Ultrasonics Symposium CY OCT 05-08, 1998 CL SENDAI, JAPAN SP IEEE, Ultrason Ferroelect & Frequency Control Soc AB Methods for fabricating and modeling high frequency 2-2 composites and arrays are presented. The composites are suitable for arrays and small aperture single element devices. Coupling coefficients above 0.65 and lateral mode frequencies near 60 MHz have been achieved. Two prototype 4 element 30 MHz linear arrays were designed and built using this composite. Backing and matching layers were fabricated and characterized while coaxial cable was used to electrically tune each element and broaden bandwidth. The measured properties of passive and active components were used to analyze the design in a time-domain finite element analysis program. Agreement between experiment and theory was excellent. C1 Penn State Univ, NIH, Bioengn Program, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Ritter, T (reprint author), Penn State Univ, NIH, Bioengn Program, Resource Ctr Med Ultrason Transducer Technol, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-4095-7 J9 ULTRASON PY 1998 BP 1851 EP 1855 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BM87A UT WOS:000079968900413 ER PT B AU Ostuni, JL Hsu, L Frank, JA AF Ostuni, JL Hsu, L Frank, JA GP IEEE IEEE TI COCGV: A method for multi-modality 3D volume registration SO 1998 INTERNATIONAL CONFERENCE ON IMAGE PROCESSING - PROCEEDINGS, VOL 2 LA English DT Proceedings Paper CT IEEE International Conference on Image Processing CY OCT 04-07, 1998 CL CHICAGO, IL SP IEEE, Signal Proc Soc AB Even with the barge quantity of registration algorithms available, there is still a significant number of potential users who are not able to grasp the technical aspects of a particular algorithm in order to use it to its full potential. Thus, in most non-ideal cases, registrations are either non-optimal or worse, unsuccessful. The COCGV algorithm is an attempt to provide an easily understandable algorithm which is accurate, fast, automatic and robust. It allows registration of volumes created using many different types of modalities and permits the user to conceptually understand how the registration is working and to visually see how the registration is progressing. C1 NIH, Lab Diagnost Radiol, Bethesda, MD 20892 USA. RP Ostuni, JL (reprint author), NIH, Lab Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-8186-8821-1 PY 1998 BP 25 EP 28 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BL76C UT WOS:000076643100006 ER PT S AU Eden, M Thevenaz, P AF Eden, M Thevenaz, P BE Wenger, E Dimitrov, LI TI History of a stochastic growth model SO 6TH INTERNATIONAL WORKSHOP ON DIGITAL IMAGE PROCESSING AND COMPUTER GRAPHICS (DIP-97): APPLICATIONS IN HUMANITIES AND NATURAL SCIENCES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 6th International Workshop on Digital Image Processing and Computer Graphics (DIP-97) - Applications in Humanities and Natural Sciences CY OCT 20-22, 1997 CL VIENNA, AUSTRIA SP Austrian Acad Sci, Inst Informat Proc, Vienna, Russian Acad Sci, Inst Informat Transmiss Problems, Moscow DE stochastic algorithms; discrete growth processes; information-lossless image coding; Eden model AB One of the earliest models of stochastic growth was originally developed for simulating the appearance of various biological patterns; in particular, bacterial colonies. Although it received little attention from biologists, some twenty years later it was adopted by crystallographers, solid state researchers, other physicists and chemists. Because of the model's flexibility it is being used by them after modifications appropriate to the application, in order to simulate their physical study objects under a variety of conditions. Only within the last few years has there been any interest in using this and similar digital models to represent the possible products of biological processes. It is also worth noting that aside from its relevance to probabilistically influenced pattern formation, the model has possible use in image processing for image compression and as an information-lossless way to code, regions, contours, or line segments. C1 NIH, Off Res Serv, Bethesda, MD 20892 USA. RP Eden, M (reprint author), NIH, Off Res Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2793-4 J9 P SOC PHOTO-OPT INS PY 1998 VL 3346 BP 43 EP 54 DI 10.1117/12.301386 PG 12 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Engineering, Electrical & Electronic; Optics SC Computer Science; Engineering; Optics GA BK61J UT WOS:000072737300004 ER PT J AU Kuroda, M Bhattacharjee, H Rosen, BP AF Kuroda, M Bhattacharjee, H Rosen, BP TI Arsenical pumps in prokaryotes and eukaryotes SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID OXYANION-TRANSLOCATING ATPASE; ESCHERICHIA-COLI; RESISTANCE OPERON; ARSA ATPASE; LEISHMANIA-TARENTOLAE; ARSENATE RESISTANCE; MEMBRANE-VESICLES; ANION PUMP; TRANSPORT; SEQUENCE C1 Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Vancouver, BC V5Z 1L3, Canada. RP Kuroda, M (reprint author), Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. NR 30 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 82 EP 97 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200007 PM 9711548 ER PT J AU Allikmets, R Dean, M AF Allikmets, R Dean, M TI Cloning of novel ABC transporter genes SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID EXPRESSED-SEQUENCE-TAGS; MULTIDRUG-RESISTANCE; CYSTIC-FIBROSIS; ANTIGEN PRESENTATION; ESCHERICHIA-COLI; P-GLYCOPROTEIN; ATP; DATABASE; YEAST; IDENTIFICATION C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. RP Allikmets, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 42 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 116 EP 130 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200009 PM 9711550 ER PT J AU Gottesman, MM Cardarelli, C Goldenberg, S Licht, T Pastan, I AF Gottesman, MM Cardarelli, C Goldenberg, S Licht, T Pastan, I TI Selection and maintenance of multidrug-resistant cells SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID GENE; EXPRESSION; TRANSPORTER; DNA C1 NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 11 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 248 EP 258 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200017 PM 9711558 ER PT J AU Dey, S Ramachandra, M Pastan, I Gottesman, MM Ambudkar, SV AF Dey, S Ramachandra, M Pastan, I Gottesman, MM Ambudkar, SV TI Photoaffinity labeling of human P-glycoprotein: Effect of modulator interaction and ATP hydrolysis on substrate binding SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID MULTIDRUG TRANSPORTER; DRUG-BINDING; RESISTANCE; ANTIBODIES; SITES; CELLS; RECONSTITUTION; PURIFICATION; BACULOVIRUS; EXPRESSION C1 NCI, Div Basic Sci, Cell Biol Labs, NIH, Bethesda, MD 20892 USA. RP Dey, S (reprint author), NCI, Div Basic Sci, Cell Biol Labs, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 20 TC 27 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 318 EP 328 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200023 PM 9711564 ER PT J AU Hrycyna, CA Ramachandra, M Pastan, I Gottesman, MM AF Hrycyna, CA Ramachandra, M Pastan, I Gottesman, MM TI Functional expression of human P-glycoprotein from plasmids using vaccinia virus bacteriophage T7 RNA polymerase system SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; CELLS; ATPASE; YEAST C1 NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hrycyna, CA (reprint author), NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 25 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 456 EP 473 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200033 PM 9711574 ER PT J AU Ambudkar, SV Lelong, IH Zhang, JP Cardarelli, C AF Ambudkar, SV Lelong, IH Zhang, JP Cardarelli, C TI Purification and reconstitution of human P-glycoprotein SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID MULTIDRUG-RESISTANCE; STREPTOCOCCUS-LACTIS; ANION-EXCHANGE; GENE; PROTEINS; CELLS; PHOSPHATE; TRANSPORT; PHOSPHORYLATION; ANTIBODIES C1 NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 36 TC 33 Z9 34 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 492 EP 504 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200036 PM 9711577 ER PT J AU Ambudkar, SV AF Ambudkar, SV TI Drug-stimulatable ATPase activity in crude membranes of human MDR1-transfected mammalian cells SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; MONOCLONAL-ANTIBODIES; PROTEINS; GENE; PHOSPHORYLATION; TRANSPORTER; HYDROLYSIS; EXPRESSION C1 NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 23 TC 105 Z9 107 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 504 EP 514 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200037 PM 9711578 ER PT J AU Sugimoto, Y Gottesman, MM Pastan, I Tsuruo, T AF Sugimoto, Y Gottesman, MM Pastan, I Tsuruo, T TI Construction of MDR1 vectors for gene therapy SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID MULTIDRUG-RESISTANCE GENE; RIBOSOME ENTRY SITE; P-GLYCOPROTEIN; RETROVIRUS VECTOR; CELLS; EXPRESSION; COEXPRESSION; CANCER; ALLOWS C1 Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Toshima Ku, Tokyo 170, Japan. Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 113, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Sugimoto, Y (reprint author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Toshima Ku, Tokyo 170, Japan. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 523 EP 537 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200039 PM 9711580 ER PT J AU Licht, T Gottesman, MM Pastan, I AF Licht, T Gottesman, MM Pastan, I TI Retroviral transfer of multidrug transporter to murine hematopoietic stem cells SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID BONE-MARROW CELLS; HUMAN MDR1 GENE; RESISTANCE GENE; TRANSGENIC MICE; P-GLYCOPROTEIN; PROGENITOR CELLS; EXPRESSION; CANCER; MOUSE; CHEMOTHERAPY C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Licht, T (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 546 EP 557 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200041 PM 9711582 ER PT J AU Lee, CGL Pastan, I Gottesman, MM AF Lee, CGL Pastan, I Gottesman, MM TI Retroviral transfer of human MDR1 gene into human T lymphocytes SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID APE LEUKEMIA-VIRUS; PACKAGING CELLS; EXPRESSION; VECTORS; TRANSDUCTION; VEHICLES; LINES; DNA C1 NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lee, CGL (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 557 EP 572 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200042 PM 9711583 ER PT J AU Evans, GL AF Evans, GL TI Construction and analysis of multidrug resistance transgenic mice SO ABC TRANSPORTERS: BIOCHEMICAL, CELLULAR, AND MOLECULAR ASPECTS SE METHODS IN ENZYMOLOGY LA English DT Review ID IN-SITU HYBRIDIZATION; HUMAN MDR1 GENE; P-GLYCOPROTEIN; BONE-MARROW; MONOCLONAL-ANTIBODIES; DRUG-RESISTANCE; CELLS; EXPRESSION; CHEMOTHERAPY; TRANSPORTER C1 Natl Ctr Human Genome Res, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. RP Evans, GL (reprint author), Natl Ctr Human Genome Res, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 292 BP 572 EP 594 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL46A UT WOS:000075571200043 PM 9711584 ER PT J AU Gonzalez, M Frank, EG McDonald, JP Levine, AS Woodgate, R AF Gonzalez, M Frank, EG McDonald, JP Levine, AS Woodgate, R TI Structural insights into the regulation of SOS mutagenesis SO ACTA BIOCHIMICA POLONICA LA English DT Article; Proceedings Paper CT Conference on Mechanisms of DNA Repair and Mutagenesis in Honor of the 100th Anniversary of the Discovery of Polonium and Radium CY OCT, 1997 CL WARSAW, POLAND DE Escherichia coli; Salmonella typhimurium; UmuD; UmuD '; ClpX; ClpP; Lon; proteolysis ID BACTERIOPHAGE-MU REPRESSOR; ESCHERICHIA-COLI; SERINE-PROTEASE; CLP PROTEASE; RECA; CLEAVAGE; UMUD; PLASMID; PROTEOLYSIS; MUTATIONS AB The Escherichia coli Umu proteins are best characterized by their role in damage inducible mutagenesis. Recently, we discovered that the intracellular levels of the UmuD and UmuC proteins are kept to a minimum by the Lon serine protease. Studies with the Salmonella typhimurium UmuD protein (which is 73% homologous with its E. coli counterpart) revealed that it too is degraded by Lon, suggesting that both UmuD proteins share conserved structural motifs. In contrast, E. coli UmuD' is removed from the cell by the ClpXP serine protease, but only when it is in a heterodimer complex with UmuD. We have generated deletion mutants of UmuD' and have coexpressed the mutant proteins with UmuD1 (a non-cleavable UmuD protein). By assaying the sensitivity of the mutant UmuD'-UmuD1 complex to ClpXP, we have been able to map regions of UmuD' that appear essential for efficient UmuD'-UmuD heterodimer formation. Previous experiments have suggested that the in vivo posttranslational processing of UmuD to UmuD' is inefficient. We have, however, discovered that limited cleavage occurs in an undamaged cell, but that these small amounts of UmuD' are rapidly degraded by ClpXP, thus giving rise to the appearance of inefficient cleavage. The ClpXP protease therefore plays dual roles in regulating SOS mutagenesis: it keeps the basal levels of UmuD' to a minimum in undamaged cells but it also acts in damaged cells to reduce the elevated levels of mutagenically active UmuD' protein, thereby returning the cell to a resting non-mutable state. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHD, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov NR 24 TC 10 Z9 10 U1 0 U2 1 PU ACTA BIOCHIMICA POLONICA PI WARSAW PA PASTEURA 3, 02-093 WARSAW, POLAND SN 0001-527X EI 1734-154X J9 ACTA BIOCHIM POL JI Acta Biochim. Pol. PY 1998 VL 45 IS 1 BP 163 EP 172 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF002 UT WOS:000072852900021 PM 9701508 ER PT J AU Solomon, D Davey, DD Nozawa, S Syrjanen, KJ AF Solomon, D Davey, DD Nozawa, S Syrjanen, KJ TI Future directions in cervical cytology SO ACTA CYTOLOGICA LA English DT Editorial Material DE cervix neoplasms; mass screening; computer-assisted diagnosis; medical laboratory technology C1 NCI, Rockville, MD 20850 USA. Lucille P Markey Canc Ctr, Dept Pathol, Lexington, KY 40507 USA. Keio Univ, Sch Med, Dept Obstet & Gynecol, Shinjuku, Tokyo 108, Japan. Univ Kuopio, Dept Pathol, FIN-70211 Kuopio, Finland. RP Solomon, D (reprint author), NCI, Rockville, MD 20850 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JAN-FEB PY 1998 VL 42 IS 1 BP 1 EP 4 PG 4 WC Pathology SC Pathology GA YZ145 UT WOS:000072224800001 PM 9479318 ER PT J AU Solomon, D Frable, WJ Vooijs, GP Wilbur, DC Amma, NS Collins, RJ Davey, DD Knight, BK Luff, RD Meisels, A Navin, J Rosenthal, DL Sauer, T Stoler, M Suprun, HZ Yamauchi, K AF Solomon, D Frable, WJ Vooijs, GP Wilbur, DC Amma, NS Collins, RJ Davey, DD Knight, BK Luff, RD Meisels, A Navin, J Rosenthal, DL Sauer, T Stoler, M Suprun, HZ Yamauchi, K TI ASCUS and AGUS criteria - IAC task force summary SO ACTA CYTOLOGICA LA English DT Article; Proceedings Paper CT Conference on Diagnostic Cytology Towards the 21st Century CY JUN 05-10, 1997 CL KAMUELA, HAWAII SP Int Acad Cytol DE cervix neoplasms; cervical smears; mass screening ID ATYPICAL SQUAMOUS CELLS; ENDOCERVICAL GLANDULAR DYSPLASIA; POTENTIAL DIAGNOSTIC PITFALL; CERVICAL SMEARS; UNDETERMINED SIGNIFICANCE; PAPANICOLAOU SMEARS; HUMAN PAPILLOMAVIRUS; CYTOLOGIC DIAGNOSIS; QUALITY ASSURANCE; TUBAL METAPLASIA AB Issues The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. Consensus Position Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms Its mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. Ongoing Issues Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, Its well Its morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have it high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings. C1 NCI, Rockville, MD 20852 USA. RP Solomon, D (reprint author), NCI, EPN Room 233,6130 Execut Blvd, Rockville, MD 20852 USA. NR 30 TC 68 Z9 73 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JAN-FEB PY 1998 VL 42 IS 1 BP 16 EP 24 PG 9 WC Pathology SC Pathology GA YZ145 UT WOS:000072224800003 PM 9479320 ER PT J AU Thomsen, S Vogt, B von Laer, D Heberlein, C Rein, A Ostertag, W Stocking, C AF Thomsen, S Vogt, B von Laer, D Heberlein, C Rein, A Ostertag, W Stocking, C TI Lack of functional Pit-1 and Pit-2 expression on hematopoietic stem cell lines SO ACTA HAEMATOLOGICA LA English DT Article; Proceedings Paper CT 10th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias and Lymphomas CY JUL 02-06, 1997 CL HAMBURG, GERMANY SP Amgen Deutschland GmbH, Rhone Poulenc Rorer GmbH DE gene transfer; hematopoietic stem cells; MLV-A; retroviral vector; Pit-1; Pit-2; VSV G protein ID APE LEUKEMIA-VIRUS; BONE-MARROW CELLS; AMPHOTROPIC RETROVIRUS RECEPTOR; PROGENITOR CELLS; MURINE LEUKEMIA; GENE-TRANSFER; ADENOSINE-DEAMINASE; SURFACE RECEPTORS; INFECTION; VECTORS AB Hematopoietic stem cells (HSC) are an important target for retroviral gene transfer. However, transduction efficiency in these HSC is extremely low compared to fibroblasts or more mature hematopoietic cells. This infection block was analyzed in the HSC line FDC-Pmix. The infection frequency with the amphotropic murine leukemia virus (MLV-A) is more than 100-fold lower in FDC-Pmix cells as compared to fibroblasts. Pseudotyping with the env of the 10A1 strain (MLV-10A1), which uses both the amphotropic receptor (Pit-2) and the receptor for gibbon ape leukemia virus (Pit-l), did not improve the infection efficiency. Vectors pseudotyped with VSV G protein were found to overcome the infection block in FDC-Pmix, confirming that the block is at the level of virus binding and possibly penetration. Accordingly, we could not detect virus binding of MLV-A or MLV-10A1 to FDC-Pmix cell lines. Northern blot analysis was performed to detect whether the defect is at the level of transcription. Surprisingly, similar levels of Pit-2 receptor transcripts were detected in all cell types. The overexpression of rat Pit-2 DNA in CHO but not in FDC-Pmix cells improved amphotropic infection frequency after introducing rat Pit-2 DNA into the cells. Taken together these results show that the inefficient infection of FDC-Pmix is due to a lack of functional receptors. Either the receptor protein is incorrectly processed in these cells or a cofactor is missing in FDC-Pmix cells that is necessary for efficient binding and/or penetration. C1 Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Mol Virol & Carcinogenesis, Frederick, MD USA. RP Thomsen, S (reprint author), Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, Martinistr 52, D-20251 Hamburg, Germany. NR 36 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1998 VL 99 IS 3 BP 148 EP 155 DI 10.1159/000040829 PG 8 WC Hematology SC Hematology GA ZH414 UT WOS:000073106600005 PM 9587396 ER PT J AU Katoh, R Suzuki, K Miyagi, E Kawaoi, A AF Katoh, R Suzuki, K Miyagi, E Kawaoi, A TI Thyroid transcription factor-1 (TTF-1) SO ACTA HISTOCHEMICA ET CYTOCHEMICA LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Japan-Society-of-Histochemistry-and-Cytochemistry CY OCT 16-17, 1997 CL MITAKA, JAPAN SP Japan Soc Histochem & Cytochem DE thyroid transcription factor 1; review; TTF-1; thyroid; in situ hybridization ID THYROTROPIN RECEPTOR GENE; ENHANCER-BINDING PROTEIN; FACTOR-I; B GENE; EXPRESSION; PROMOTER; LUNG; SPECIFICITY; HOMEODOMAIN; REGIONS AB Thyroid transcription factor 1 (TTF-1), as noted earlier, is a "thyroid specific" transcription factor that is a homeodomain-containing protein responsible for transcriptional activation of thyroid-specific genes, thyroglobulin (Tg), thyroperoxidase (TPO), and thyrotropin receptor (TSHr) genes, in thyroid follicular cells. Little is known about the histological localization or distribution of TTF-1 protein and mRNA, even though many papers on TTF-1 have been published in the past ten years. Therefore, we decided to examine the expression of TTF-1mRNA in normal and neoplastic thyroid tissues using immunohistochemistry and in situ hybridization as well as molecular techniques such as Northern blot and RT-PCR. In addition, extrathyroidal expression of TTF-1 was also investigated in some organs. In this paper, we reviewed literature and discussed the role of TTF-1 in thyroid hormonogenesis, and presented its precise localization or distribution in normal and neoplastic thyroid tissues. In addition, extrathyroidal expression of TTF-1 is briefly discussed. C1 Yamanashi Med Univ, Sch Med, Dept Pathol, Yamanashi 4093895, Japan. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Katoh, R (reprint author), Yamanashi Med Univ, Sch Med, Dept Pathol, 1110 Shimokato,Tamaho Cho, Yamanashi 4093895, Japan. NR 18 TC 1 Z9 1 U1 2 U2 2 PU JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY PI KYOTO PA C/O NAKANISHI PRINTING CO LTD, SHIMODACHIURI-OGAWA, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0044-5991 EI 1347-5800 J9 ACTA HISTOCHEM CYTOC JI Acta Histochem. Cytochem. PY 1998 VL 31 IS 4 BP 287 EP 290 PG 4 WC Cell Biology SC Cell Biology GA 125ZL UT WOS:000076267700006 ER PT J AU Maser, JD AF Maser, JD TI Generalized anxiety disorder and its comorbidities: disputes at the boundaries SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE generalized anxiety disorder; panic disorder; diagnosis; classification ID ALPHA-2-ADRENERGIC RECEPTOR-BINDING; PANIC DISORDER; PERSONALITY-DISORDERS; IDEATIONAL COMPONENTS; PSYCHIATRIC-DISORDERS; PLASMA-CATECHOLAMINES; GENETIC-FACTORS; DOUBLE-BLIND; AXIS-I; AGORAPHOBIA AB This theoretical paper reviews the status of generalized anxiety disorder (GAD) and the Axis I and Axis II disorders with which it is often comorbid. Differences in comorbidity between the epidemiological and clinical literatures are discussed. Special attention is given to panic disorder, the symptoms of which are similar to those of GAD. The boundaries of GAD and its relationship to other Axis I disorders and to Axis II disorders raise important implications for its classification. C1 NIMH, Anxiety & Somatoform Disorders Program, Rockville, MD 20857 USA. RP Maser, JD (reprint author), NIMH, Anxiety & Somatoform Disorders Program, 5600 Fishers Lane,Room 10C 16, Rockville, MD 20857 USA. NR 99 TC 17 Z9 17 U1 6 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 1998 VL 98 SU 393 BP 12 EP 22 DI 10.1111/j.1600-0447.1998.tb05961.x PG 11 WC Psychiatry SC Psychiatry GA 121FA UT WOS:000076001600004 PM 9777042 ER PT S AU Snyderwine, EG AF Snyderwine, EG BE Senn, HJ Gelber, R Goldhirsch, A Thurlimann, B TI Diet and mammary gland carcinogenesis SO ADJUVANT THERAPY OF PRIMARY BREAST CANCER VI SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT Adjuvant Therapy for Primary Breast Cancer Conference CY FEB 25-28, 1998 CL ST GALLEN, SWITZERLAND ID BREAST-CANCER RISK; HETEROCYCLIC AMINES; AMERICAN WOMEN; FAT; WEIGHT C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, Expt Carcinogenesis Lab, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. NR 31 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-64085-1 J9 RECENT RES CANCER PY 1998 VL 152 BP 3 EP 10 PG 8 WC Oncology SC Oncology GA BM35K UT WOS:000078457400001 PM 9928542 ER PT S AU Abrams, JS AF Abrams, JS BE Senn, HJ Gelber, R Goldhirsch, A Thurlimann, B TI North American adjuvant breast cancer trials SO ADJUVANT THERAPY OF PRIMARY BREAST CANCER VI SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT Adjuvant Therapy for Primary Breast Cancer Conference CY FEB 25-28, 1998 CL ST GALLEN, SWITZERLAND ID RECEPTOR-NEGATIVE TUMORS; SEQUENTIAL METHOTREXATE; SURVIVAL; EFFICACY; THERAPY; CYCLOPHOSPHAMIDE; FLUOROURACIL; DOXORUBICIN; MICE C1 NCI, Clin Invest Branch, Bethesda, MD 20892 USA. RP Abrams, JS (reprint author), NCI, Clin Invest Branch, 6130 Execut Blvd,741, Bethesda, MD 20892 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-64085-1 J9 RECENT RES CANCER PY 1998 VL 152 BP 417 EP 428 PG 12 WC Oncology SC Oncology GA BM35K UT WOS:000078457400040 PM 9928576 ER PT J AU Zbar, B Lerman, M AF Zbar, B Lerman, M TI Inherited carcinomas of the kidney SO ADVANCES IN CANCER RESEARCH, VOL 75 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID RENAL-CELL-CARCINOMA; TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU DISEASE; RECEPTOR TYROSINE KINASE; HEPATOCYTE GROWTH-FACTOR; MOLECULAR DIFFERENTIAL-DIAGNOSIS; TUBEROUS-SCLEROSIS-2 TSC2 GENE; FACTOR SCATTER FACTOR; EKER RAT MODEL; SOMATIC MUTATIONS C1 NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Zbar, B (reprint author), NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 177 TC 39 Z9 39 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1998 VL 75 BP 163 EP 201 DI 10.1016/S0065-230X(08)60742-3 PG 41 WC Oncology SC Oncology GA BM54X UT WOS:000079074200005 PM 9709810 ER PT S AU Cocco, L Capitani, S Maraldi, NM Mazzotti, G Barnabei, O Rizzoli, R Gilmour, RS Wirtz, KWA Rhee, SG Manzoli, FA AF Cocco, L Capitani, S Maraldi, NM Mazzotti, G Barnabei, O Rizzoli, R Gilmour, RS Wirtz, KWA Rhee, SG Manzoli, FA BE Weber, G Weber, CEF TI Inositides in the nucleus: Taking stock of PLC beta(1) SO ADVANCES IN ENZYME REGULATION, VOL 38 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 38th Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 29-30, 1997 CL INDIANA UNIV SCH MED, INDIANAPOLIS, INDIANA HO INDIANA UNIV SCH MED ID PHOSPHATIDYLINOSITOL-TRANSFER PROTEIN; PHOSPHOLIPASE-C BETA(1); RAT-LIVER NUCLEI; SWISS 3T3 CELLS; FRIEND-CELLS; KINASE-C; DNA-SYNTHESIS; IGF-I; DIFFERENTIATION; ISOFORM C1 Univ Bologna, Inst Human Anat, I-40126 Bologna, Italy. Univ Ferrara, Inst Human Anat, I-44100 Ferrara, Italy. CNR, Inst Cytomorphol, Chieti, Italy. CNR, Inst Cytomorphol, I-40126 Bologna, Italy. IOR, Bologna, Italy. Univ Bologna, Dept Biol, I-40126 Bologna, Italy. Univ Chieti, Inst Human Morphol, Chieti, Italy. Univ Auckland, Sch Med, Dept Mol Med, Auckland 1, New Zealand. Univ Utrecht, CBLE, NL-3508 TC Utrecht, Netherlands. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. RP Cocco, L (reprint author), Univ Bologna, Inst Human Anat, I-40126 Bologna, Italy. NR 38 TC 16 Z9 16 U1 1 U2 1 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 J9 ADV ENZYME REGUL PY 1998 VL 38 BP 351 EP 363 DI 10.1016/S0065-2571(97)00014-9 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL74F UT WOS:000076528700020 PM 9762362 ER PT S AU Marchalonis, JJ Schluter, SF Bernstein, RM Shen, SX Edmundson, AB AF Marchalonis, JJ Schluter, SF Bernstein, RM Shen, SX Edmundson, AB BE Dixon, FJ TI Phylogenetic emergence and molecular evolution of the immunoglobulin family SO ADVANCES IN IMMUNOLOGY, VOL 70 SE Advances in Immunology LA English DT Review ID T-CELL RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; TROUT ONCORHYNCHUS-MYKISS; VERTEBRATE IMMUNE-SYSTEM; LIGHT-CHAIN GENES; IG HEAVY-CHAIN; COMPLETE NUCLEOTIDE-SEQUENCE; JOINING SEGMENT PEPTIDE; VARIABLE REGION GENES; AMINO-ACID-SEQUENCE C1 Univ Arizona, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RP Marchalonis, JJ (reprint author), Univ Arizona, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. FU NCI NIH HHS [CA72803] NR 277 TC 69 Z9 73 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022470-4 J9 ADV IMMUNOL JI Adv.Immunol. PY 1998 VL 70 BP 417 EP 506 DI 10.1016/S0065-2776(08)60392-2 PG 90 WC Immunology SC Immunology GA BM62R UT WOS:000079287100007 PM 9755343 ER PT S AU Teng, C Shi, HP Yang, NY Shigeta, H AF Teng, C Shi, HP Yang, NY Shigeta, H BE Spik, G Legrand, D Mazurier, J Pierce, A Perraudin, JP TI Mouse lactoferrin gene - Promoter-specific regulation by EGF and cDNA cloning of the EGF-response-element binding protein SO ADVANCES IN LACTOFERRIN RESEARCH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Congress on Lactoferrin Structure and Function CY MAY 05-09, 1997 CL LE TOUQUET, FRANCE SP Morinaga Milk Ind Co, DMV Int, Agennix Inc, Armor Proteines, Biopole, Domo, Ferro Dynamics, Gist Brocades, Nutricia Milupa Res, Pharming BV, Tatua Biol, Tonipharm Lab, Wyeth Ayerst Res, Univ Sci & Technol Lille, CNRS ID EPIDERMAL GROWTH-FACTOR; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; SIGNALING PATHWAYS; TRANSIN GENE; EXPRESSION; REGION; LACTOTRANSFERRIN; REQUIREMENT; CONSTRAINTS AB Expression of the lactoferrin gene in a variety of tissues is regulated differentially We have previously demonstrated that the lactoferrin gene is regulated by estrogen and mitogen in mouse uterus. The mouse lactoferrin gene responded to forskolin, cAMP TPA and EGF stimulation via two adjacent enhancer elements, the CRE and EGFRE and collectively referred to as the Mitogen Response Unit (MRU). We found that CRE is responsible for forskolin, cAMP and TPA whereas EGFRE is for EGF stimulation. We examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the CAT reporter construct, whereas, the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters (SV 40 and TK). Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. Mutation made at either elements or insertion of extra nucleotides between the two elements, severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells protected the EGFRE, CRE and noncanonical TATA from DNAase I digestion in a footprinting analysis. Nuclear protein which interacted with the CRE were previously identified as AP1 and CREB. In this study, we isolated a cDNA clone from an RL95-2 expression library that encodes the EG FRE binding protein. Partial sequence of the cDNA clone revealed 100% nucleotide identity with a GC-box binding protein, BTEB2. Protein-protein interaction among the transcription factors could fine-tune the mouse lactoferrin expression in various tissues. C1 NIEHS, Reprod & Dev Toxicol Lab, Gene Regulat Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, C (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Gene Regulat Grp, NIH, Res Triangle Pk, NC 27709 USA. NR 39 TC 10 Z9 10 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 0-306-45926-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 443 BP 65 EP 78 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BL64L UT WOS:000076156300008 PM 9781344 ER PT S AU Ward, PP Mendoza, MM Saucedo-Cardenas, O Teng, CT Conneely, OM AF Ward, PP Mendoza, MM Saucedo-Cardenas, O Teng, CT Conneely, OM BE Spik, G Legrand, D Mazurier, J Pierce, A Perraudin, JP TI Restricted spatiotemporal expression of lactoferrin during murine embryogenesis SO ADVANCES IN LACTOFERRIN RESEARCH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Congress on Lactoferrin Structure and Function CY MAY 05-09, 1997 CL LE TOUQUET, FRANCE SP Morinaga Milk Ind Co, DMV Int, Agennix Inc, Armor Proteines, Biopole, Domo, Ferro Dynamics, Gist Brocades, Nutricia Milupa Res, Pharming BV, Tatua Biol, Tonipharm Lab, Wyeth Ayerst Res, Univ Sci & Technol Lille, CNRS ID ESCHERICHIA-COLI; STEM-CELLS; LACTOTRANSFERRIN; RECEPTORS; BINDING; HEMATOPOIESIS; LOCALIZATION; RELEASE; PROTEIN; REGION AB Lactoferrin is a member of the transferrin family of iron-binding proteins to which several physiological functions have been ascribed. While there is a wealth of evidence about the distribution and function of this protein in the adult, the expression and function, if any, of lactoferrin during embryogenesis has not been investigated. In the current study, the spatiotemporal distribution of lactoferrin was analyzed during normal murine embryonic development. This analysis demonstrated that lactoferrin is expressed in three distinct patterns during embryogenesis. First, lactoferrin is expressed at the 2-cell stage in the preimplantation embryo where it continues to be expressed until the blastocyst stage when expression ceases. The second phase of lactoferrin expression is not detected until the latter half of gestation when the protein is detected in the myeloid cells, beginning in the fetal liver at embryonic day 11 and later in the spleen and bone marrow coinciding with the onset and diversification of myelopoiesis in these organs during embryogenesis. Finally, lactoferrin is detected in a variety of glandular epithelial cells and/or their secretions, including respiratory and oral epithelia which is consistent with the expression pattern observed for this protein in the adult where it plays an important role in host defense at the mucosal surface. Taken together, these analyses indicate that the role of lactoferrin in the developing embryo is restricted to the preimplantation stage and development of first and second line host defense systems. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Ward, PP (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 45 TC 4 Z9 4 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 0-306-45926-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 443 BP 91 EP 100 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BL64L UT WOS:000076156300011 PM 9781347 ER PT B AU Zahn-Waxler, C McBride, A AF Zahn-Waxler, C McBride, A BE Adair, JG Belanger, D Dion, KL TI Current perspectives on social and emotional development SO ADVANCES IN PSYCHOLOGICAL SCIENCE, VOL 1: SOCIAL, PERSONAL AND CULTURAL ASPECTS LA English DT Proceedings Paper CT 26th International Congress of Psychology CY AUG 16-21, 1996 CL MONTREAL, CANADA SP Canadian Psychol Assoc, NRC Canada, Int Union Psychol Sci ID PARENT-CHILD INTERACTION; BEHAVIOR PROBLEMS; GENDER DIFFERENCES; PERSONALITY-DEVELOPMENT; INDIVIDUAL-DIFFERENCES; PRESCHOOL-CHILDREN; CONDUCT DISORDER; MOTHER-CHILD; DEPRESSIVE SYMPTOMS; ANTISOCIAL-BEHAVIOR AB Research on social-emotional development is increasingly characterized by a multivariate approach, an interdisciplinary focus, and a developmental psychopathology perspective. There is an emphasis on the interaction of biological and environmental factors that produce normative and maladaptive patterns of development. Current conceptual frameworks are reviewed and the range of domains considered within the area of social-emotional development are briefly described. Recent investigations of emotional, prosocial, and antisocial development are examined in greater detail. Exemplars of developmental psychopathology research that are considered focus on outcomes for children and adolescents exposed to marital discord and parental depression. Processes implicated in the development of different types of social, emotional and behavioral styles and problems in males and females are discussed. C1 NIMH, Bethesda, MD 20892 USA. NR 131 TC 0 Z9 0 U1 7 U2 13 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND BN 0-86377-470-9 PY 1998 BP 513 EP 546 PG 34 WC Psychology, Multidisciplinary; Psychology, Social SC Psychology GA BP78E UT WOS:000086166200025 ER PT S AU Jones, S Yakel, JL AF Jones, S Yakel, JL BE Martin, GR Eglen, RM Hoyer, D Hamblin, MW Yocca, F TI Calcium influx through voltage-gated calcium channels regulates 5-HT3 receptor channel desensitization in NG108-15 cells SO ADVANCES IN SEROTONIN RECEPTOR RESEARCH: MOLECULAR BIOLOGY, SIGNAL TRANSDUCTION, AND THERAPEUTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Meeting Abstract CT Conference on Advances in Serotonin Receptor Research - Molecular Biology, Signal Transduction, and Therapeutics CY OCT 08-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Serotonin Club, Int Union Pharmacol, Roche Biosci, Palo Alto, Bristol Myers Squibb, Wallingford, DuPont Merck Pharmaceut Co, Wilmington, F Hoffmann La Roche, Basel, Lilly Res Labs, Indianapolis, Novartis Pharma AG, Basel, Pfizer Cent Res, Groton, SmithKline Beecham, Harlow, Glaxo Wellcome, Stevenage, Merck Res Labs, Harlow, Pierre Fabre, Castres C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 2 TC 2 Z9 2 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 1-57331-170-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 861 BP 253 EP 254 DI 10.1111/j.1749-6632.1998.tb10208.x PG 2 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BM29R UT WOS:000078304800042 PM 9928274 ER PT J AU Nguyen, BY Clerici, M Venzon, DJ Bauza, S Murphy, WJ Longo, DL Baseler, M Gesundheit, N Broder, S Shearer, G Yarchoan, R AF Nguyen, BY Clerici, M Venzon, DJ Bauza, S Murphy, WJ Longo, DL Baseler, M Gesundheit, N Broder, S Shearer, G Yarchoan, R TI Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin-like growth factor in HIV-infected patients SO AIDS LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Laboratory-of-Tumor-Cell-Biology CY AUG, 1995 CL BETHESDA, MARYLAND SP Lab Tumor Cell Biol DE growth hormone; insulin-like growth factor; immunotherapy; T-cell subset; immune reconstitution; wasting; therapy; cellular immunity ID IMMUNODEFICIENCY-VIRUS INFECTION; IMMUNE-DEFICIENCY SYNDROME; PLACEBO-CONTROLLED TRIAL; IGF-BINDING PROTEINS; T-CELL DEVELOPMENT; FACTOR-I; NEUROENDOCRINE HORMONES; THYMUS GLAND; MURINE; AIDS AB Objective: To study the immunologic effects of recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the combination, in patients with moderately advanced HIV infection. Design: Randomized but not blinded trial. Setting: Government medical research center. Patients: Twenty-four HIV-infected patients with CD4 cell counts of 100-400 x 10(6)/l who were receiving nucleoside antiretroviral therapy. Interventions: Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12 weeks. Main outcome measures: Immunologic parameters, including T-cell subsets and assays of in vitro interleukin (IL)-2 production in response to antigens and mitogens, and safety profile. Results: Plasma IGF-1 levels were low or low-normal prior to treatment and increased with all three therapies. There were no significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer cell function, immunoglobulin levels, or in vitro IL-2 production in response to mitogen or alloantigens. However, there was an upward trend (and for p18(IIIB) a statistically significant increase) in the in vitro IL-2 production in response to each of five HIV envelope peptides. Potential toxic effects included fatigue, arthralgia, edema, myalgia, and headache. Patients also were noted to have weight gain averaging 4 kg early in the course of treatment. Conclusions: These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NCI, Sci Applicat Int Corp Frederick, Frederick, MD USA. Genentech Inc, S San Francisco, CA 94080 USA. NCI, Off Director, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 45 TC 35 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PY 1998 VL 12 IS 8 BP 895 EP 904 DI 10.1097/00002030-199808000-00012 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZN841 UT WOS:000073688000012 PM 9631143 ER PT J AU VanDevanter, N Cleary, PD Moore, J Thacker, AS O'Brien, TR AF VanDevanter, N Cleary, PD Moore, J Thacker, AS O'Brien, TR TI Reproductive behavior in HIV-discordant heterosexual couples: Implications for counseling SO AIDS PATIENT CARE AND STDS LA English DT Article ID INTRAVENOUS DRUG-USERS; SEXUAL-BEHAVIOR; WOMEN; PREGNANCY; RISK; SUSCEPTIBILITY; TRANSMISSION; KNOWLEDGE; DECISIONS; INFECTION AB The development of effective behavioral interventions is critical to controlling the HIV epidemic. Although heterosexual transmission accounts for a growing proportion of new infections in the United States, little is known about factors that influence sexual behavior in HIV-discordant heterosexual couples. The objective of this study was to examine the reproductive behaviors of HIV-discordant heterosexual couples. Data were obtained on 71 discordant couples enrolled in a study of HIV heterosexual transmission. Results showed that women in such couples have pregnancy rates similar to those of women of reproductive age in the general population. One seroconversion occurred as a result of pregnancy attempt. These results suggest the need for educational efforts directed at HIV-discordant heterosexual couples. C1 Columbia Univ, Sch Publ Hlth, Div Sociomed Sci, New York, NY 10032 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Natl Canc Inst, Bethesda, MD USA. RP VanDevanter, N (reprint author), Columbia Univ, Sch Publ Hlth, Div Sociomed Sci, 600 W 168th St, New York, NY 10032 USA. FU PHS HHS [U64-CCU20486] NR 36 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 1998 VL 12 IS 1 BP 43 EP 49 DI 10.1089/apc.1998.12.43 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA YW317 UT WOS:000071921800007 PM 11361885 ER PT J AU Chaix-Baudier, ML Chappey, C Burgard, M Letourneur, F Igual, J Saragosti, S Rouzioux, C AF Chaix-Baudier, ML Chappey, C Burgard, M Letourneur, F Igual, J Saragosti, S Rouzioux, C CA French HIV Pediat Cohort Study Grp TI First case of mother-to-infant HIV type 1 group O transmission and evolution of C2V3 sequences in the infected child SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUBTYPE-O; PHYLOGENETIC ANALYSIS; ZIDOVUDINE TREATMENT; GENETIC-ANALYSIS; STRAINS; INVIVO; IDENTIFICATION; GLYCOSYLATION; DIVERSITY AB We report the first case of mother-to-infant transmission and follow-up for an HIV-1 group O virus from Cameroon, Isolates were obtained from the mother at delivery and from the child at birth and when 16 and 30 months old, We analyzed the viral evolution within mother and child by examining 51 sequences spanning C2V3 regions of the viral envelope gene, The mother carried two genotypes, vl and v2, The genotype vl was dominant in the child at birth, and persisted as a minor genotype at age 30 months, The genotype v2 was absent in the child sequences, The variability of the nucleotide sequences of the isolates from the child increased with age from 0.8 to 6%, and a novel genotype (v3) appeared at age 30 months, The nonsynonymous-to-synonymous mutation ratio increased with the age of the child, from 0.75 at birth to 1.86 at 30 months, indicating a high rate of fixation of amino acid changes in the child. The overall pattern was similar to that reported by Ganeshan et al.(1) (J Virol 1997;71:663-677) for group M viruses infecting child with a slow-developing form of the disease. C1 Hop Necker Enfants Malad, Virol Lab, F-75015 Paris, France. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Inst Cochin Genet Mol, F-75014 Paris, France. Hop Laennec, Serv Pneumol, F-75007 Paris, France. RP Chaix-Baudier, ML (reprint author), Hop Necker Enfants Malad, Virol Lab, 149 Rue Sevres, F-75015 Paris, France. NR 50 TC 15 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1998 VL 14 IS 1 BP 15 EP 23 DI 10.1089/aid.1998.14.15 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YQ462 UT WOS:000071390000003 PM 9453247 ER PT J AU Al-Harthi, L Owais, M Arya, SK AF Al-Harthi, L Owais, M Arya, SK TI Molecular inhibition of HIV type 1 by HIV type 2: Effectiveness in peripheral blood mononuclear cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSACTIVATOR TAT; MIXED INFECTIONS; COTE-DIVOIRE; WEST-AFRICA; GENE; RETROVIRUSES; EXPRESSION; RECEPTOR; SPREAD AB HIV-2 downregulates HIV-1 in human primary peripheral blood mononuclear cells (PBMCs), Although the effect of HIV-2 on HIV-1 in human CD4(+) T cell lines was previously reported, the present observations with PBMCs are a necessary demonstration before considering animal model and clinical studies, Notably, the downregulation was observed with at least three phenotypically different HIV-1 proviruses and three different HIV-2 proviruses and was independent of the mode of introduction of the proviruses. HIV-2 inhibited both the production of extracellular HIV-1 p24 antigen and intracellular viral RNA, suggesting the involvement of transcriptional downmodulation, Some of the defective HIV-2 proviruses also inhibited HIV-1. In some cases, these defects mere transcomplemented by the corresponding HIV-1 gene products, emphasizing cross-regulation between the two viruses, The phenotype of one of the mutant HIV-2 proviruses suggested that the posttranscriptional effects may also occur, In addition to the possible HIV-2 suppression of HIV-1 in vivo by cross-protective immune mechanisms, intracellular inhibition, noted here, may be another line of defense, We have proposed that the inhibition may be the result of competition between HIV-1 and HIV-2 for cellular factors, possibly involving the long terminal repeats (LTRs), For safety reasons, it may be advantageous to use subunits of HIV-2 for vaccines and gene therapy, HIV-2, specifically noncytopathic HIV-2, could be viewed as an attenuated HIV-1 vaccination model, HIV-2-derived gene transfer vectors may not only be inhibitory themselves but also allow for the insertion of additional protective genes to aim at multiple targets in the HIV-1 life cycle, thus curtailing the evolution of escape mutants. C1 NCI, Div Basic Sci, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Arya, SK (reprint author), NCI, Div Basic Sci, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1998 VL 14 IS 1 BP 59 EP 64 DI 10.1089/aid.1998.14.59 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YQ462 UT WOS:000071390000008 PM 9453252 ER PT J AU Grant, BF AF Grant, BF TI The impact of a family history of alcoholism on the relationship between age at onset of alcohol use and DSM-IV alcohol dependence - Results from the National Longitudinal Alcohol Epidemiologic Survey SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE family AODU (alcohol and other drug use) history; AOD dependence; AOD use initiation; prevalence; age; disease onset; risk assessment; risk factors; diagnostic criteria; survey; longitudinal study AB Both the age at onset of alcohol use and a family history of alcoholism can influence a person's risk of becoming alcohol dependent. The relationship between lifetime alcohol dependence, age at first alcohol use, and a family history of alcoholism was investigated using data obtained in the 1992 National Longitudinal Alcohol Epidemiologic Survey. This analysis demonstrated that regardless of the family history of alcoholism, respondents with an earlier age of drinking onset were more likely to become alcohol dependent compared with respondents with a later age of drinking onset. Among all age, race, and gender subgroups studied however, people with a family history of alcoholism had a higher prevalence of lifetime alcohol dependence than did people without such a history. C1 NIAAA, Div Biometry & Epidemiol, Biometry Branch, Bethesda, MD 20205 USA. RP Grant, BF (reprint author), NIAAA, Div Biometry & Epidemiol, Biometry Branch, Bethesda, MD 20205 USA. NR 8 TC 102 Z9 106 U1 0 U2 3 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1998 VL 22 IS 2 BP 144 EP 147 PG 4 WC Substance Abuse SC Substance Abuse GA 165AG UT WOS:000078495700008 PM 15706789 ER PT J AU Longnecker, MP Tseng, M AF Longnecker, MP Tseng, M TI Alcohol, hormones, and postmenopausal women SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE AODE (alcohol and other drug effects); menopause; female; sex hormones; estrogens; mammary gland; neoplastic disease; cardiovascular disorder; moderate AOD use; drug therapy; literature review ID CORONARY HEART-DISEASE; MENOPAUSAL TRANSITION; BREAST-CANCER; SEX-HORMONES; US ADULTS; MORTALITY; EPIDEMIOLOGY; CONSUMPTION; INGESTION; ESTROGEN AB Many women fake supplemental estrogens after menopause, a practice called hormone replacement therapy (HRT). Moderate alcohol consumption may increase estrogen levels in women receiving HRT, potentially affecting their risk for various adverse health effects. Two recent studies, however, provide no strong evidence for an effect of alcohol on hormones in postmenopausal women. The possible association between alcohol consumption and risk of cancer of the breast does not appear to be mediated by estrogens. Both estrogens and moderate alcohol consumption have been associated with a decreased risk for cardiovascular disease; however, alcohol's beneficial effect on heart disease does not appear to involve hormonal mechanisms. Additional research is needed to define the consequences of moderate drinking on hormone levels after menopause. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RI Tseng, Marilyn/B-9334-2016; OI Tseng, Marilyn/0000-0002-9969-9055; Longnecker, Matthew/0000-0001-6073-5322 NR 28 TC 11 Z9 12 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1998 VL 22 IS 3 BP 185 EP 189 PG 5 WC Substance Abuse SC Substance Abuse GA 190FZ UT WOS:000079953200005 PM 15706794 ER PT J AU Stewart, CA Termanini, B Sutliff, VE Serrano, J Yu, F Gibril, F Jensen, RT AF Stewart, CA Termanini, B Sutliff, VE Serrano, J Yu, F Gibril, F Jensen, RT TI Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID OMEPRAZOLE THERAPY; SERUM FERRITIN; CLINICAL-EVALUATION; FOOD IRON; INHIBITION; STORES; HYPERGASTRINEMIA; VITAMIN-B12; DEFICIENCY AB Background: Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection, It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. Aim: To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. Methods: One hundred and nine patients with ZES but without previous gastric resections were studied, All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio), Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. Results: Eighty-nine patients were taking omeprazole nine patients were taking histamine Hz-antagonists and 11 patients were taking no drugs following curative resection, The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years).,Acid hyposecretion was present by at least one criterion in 45% of patients, There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency, Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency, Conclusions: Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency, These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B-12 in such patients is needed, such monitoring for iron parameters is not necessary. C1 NIDDK, DDB, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, DDB, NIH, Bldg 10,Rm 9C103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 68 TC 49 Z9 51 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN PY 1998 VL 12 IS 1 BP 83 EP 98 PG 16 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA YV767 UT WOS:000071861000013 PM 9692706 ER PT J AU Helm, BA Sayers, I Padlan, EA McKendrick, JE Spivey, AC AF Helm, BA Sayers, I Padlan, EA McKendrick, JE Spivey, AC TI Structure/function studies on IgE as a basis for the development of rational IgE antagonists SO ALLERGY LA English DT Article; Proceedings Paper CT International Jubilee Symposium - 30 Years with IgE CY SEP 01-02, 1998 CL STOCKHOLM, SWEDEN ID HIGH-AFFINITY RECEPTOR; PEPTIDE COMBINATORIAL LIBRARIES; FC-EPSILON-RI; HUMAN-IMMUNOGLOBULIN-E; BINDING-SITE; COMPLEX; DESIGN; IDENTIFICATION; NONPEPTIDE; PARASITES C1 Univ Sheffield, Dept Mol Biol & Biotechnol, Krebs Inst Biomol Res, Sheffield, S Yorkshire, England. NIH, Mol Biol Lab, Bethesda, MD USA. Univ Sheffield, Dept Chem, Sheffield, S Yorkshire, England. RP Helm, BA (reprint author), Univ Sheffield, Dept Mol Biol & Biotechnol, Krebs Inst Biomol Res, Sheffield, S Yorkshire, England. FU Wellcome Trust NR 54 TC 3 Z9 3 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 PY 1998 VL 53 SU 45 BP 77 EP 82 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 128MZ UT WOS:000076411700015 PM 9788713 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Ernest W. Hornung (1866-1921) - British author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 1998 VL 19 IS 1 BP 31 EP 34 DI 10.2500/108854198778557944 PG 8 WC Allergy SC Allergy GA ZC490 UT WOS:000072584900006 ER PT J AU Stewart, PA Stewart, WF Siemiatycki, J Heineman, EF Dosemeci, M AF Stewart, PA Stewart, WF Siemiatycki, J Heineman, EF Dosemeci, M TI Questionnaires for collecting detailed occupational information for community-based case control studies SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article DE case control studies; exposure; questionnaires ID REPORTED WORK HISTORY; EXPOSURE DATA; SURROGATE RESPONDENTS; VALIDITY; INTERVIEW; DISEASE; CANCER; MEMORY AB In case control studies, collection of information on the workplace environment has generally been limited to self-reports of exposures or to job title, type of employer, and the dates the jobs were held, supplemented sometimes by work activities. This information, however, may be insufficient to assess the potential and level of exposure accurately due to recall difficulties and the variability of exposures within a job. A solution to this problem is to use job-specific questionnaires. The organization of a series of such questionnaires developed for a case control study of brain tumors is described. Three types of questionnaires, or modules, were developed: task-based, industry-based, and modules based on jobs with nonspecific types of tasks (e.g., laborer). The format of these modules starts with questions on the general work environment (type of employer) and proceeds to questions on tasks. More detailed information is then gathered on materials and equipment used, sensory descriptions, dermal exposure, work practices, engineering controls, and personal protective equipment use. The questionnaires cover a wide variety of exposures including solvents, heavy metals, polycyclic aromatic hydrocarbons, machining fluids, electromagnetic frequency fields, and many other exposures and, therefore, can be used in other case control studies. C1 NEI, Occupat Studies Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Inst Armand Frappier, Quebec City, PQ, Canada. RP Stewart, PA (reprint author), NEI, Occupat Studies Sect, EPN 418,6130 Execut Blvd,MSC 7364, Bethesda, MD 20892 USA. NR 31 TC 45 Z9 45 U1 2 U2 5 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD JAN PY 1998 VL 59 IS 1 BP 39 EP 44 DI 10.1080/15428119891010325 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA YQ457 UT WOS:000071389500009 PM 9438334 ER PT J AU Forman, MR Johnson, EJ Lanza, E Graubard, BI Beecher, GR Muesing, R AF Forman, MR Johnson, EJ Lanza, E Graubard, BI Beecher, GR Muesing, R TI Effect of menstrual cycle phase on the concentration of individual carotenoids in lipoproteins of premenopausal women: a controlled dietary study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE carotenoids; lipoproteins; menstrual cycle; premenopausal women; controlled diet; Carotenoid, Lipids, Hormones Study ID HIGH-DENSITY-LIPOPROTEINS; BETA-CAROTENE; CORPUS-LUTEUM; HUMAN-PLASMA; LUTEINIZING-HORMONE; ALPHA-TOCOPHEROL; VITAMIN-A; SUPPLEMENTATION; SEPARATION; INVITRO AB Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it is hypothesized that carotenoid concentrations in lipoprotein fractions fluctuate by phase of the menstrual cycle. Nine women ate a standard set of carotenoid-rich foods daily for two cycles under isoenergetic conditions. In the second cycle, hormones and carotenoids in lipoprotein fractions were measured in the early and late follicular and luteal phases. alpha-Carotene concentrations in the LDL fraction were lower in the early than in the late follicular phase (P = 0.03) on the basis of regression analysis. beta-carotene concentrations in the LDL fraction and the HDL2 subfraction were higher in the late follicular than in the luteal phase (P = 0.02 and P = 0.04, respectively). Lutein/zeaxanthin concentrations in the LDL and HDL fractions were higher in the late follicular than in the luteal phase (P = 0.03 and P = 0.02, respectively). In each phase, 80% of alpha-carotene, 82% of beta-carotene, 85% of lycopene, and 64% of lutein/zeaxanthin were distributed in the LDL fraction. Among the hydrocarbon cartenoids, 18% of alpha-carotene and of beta-carotene and 13% of lycopene were distributed in the HDL fraction, with slightly more in the HDL2 than in the HDL3 subfraction. In contrast 34% of lutein/zeaxanthin was distributed in the HDL fraction with more concentrated in the HDL3.than in the HDL2 subfraction. Less than 4% of any carotenoid was found in the VLDL+IDL (intermediate-density-lipoprotein) fractions. Thus, the hydrocarbon carotenoids were highly concentrated in the LDL fraction and xanthophyll was more evenly distributed in the LDL and HDL fractions. The cyclic fluctuations of these carotenoids in lipoprotein fractions add another dimension to the understanding of their transport and physiologic function. C1 NCI, DCPC, CPRP, CPSB, Bethesda, MD 20892 USA. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Agr Res Serv, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. George Washington Univ, Med Ctr, Dept Med, Lipid Res Clin Lab, Washington, DC 20037 USA. RP Forman, MR (reprint author), NCI, DCPC, CPRP, CPSB, Execut Plaza N,Suite 211,6130 Execut Blvd MSC 732, Bethesda, MD 20892 USA. EM mf63p@nih.gov NR 42 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1998 VL 67 IS 1 BP 81 EP 87 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YQ214 UT WOS:000071362100016 PM 9440379 ER PT J AU Mingrone, G Benedetti, G Capristo, E De Gaetano, A Greco, AV Tataranni, PA Gasbarrini, G AF Mingrone, G Benedetti, G Capristo, E De Gaetano, A Greco, AV Tataranni, PA Gasbarrini, G TI Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE Crohn disease; respiratory chamber; 24-h energy expenditure; metabolizable energy; energy balance; steroid therapy; body composition; prednisone; humans ID INFLAMMATORY BOWEL-DISEASE; EXPENDITURE; MUSCLE; INVIVO AB Several hypotheses have been proposed to explain the nutritional deficiencies seen in Crohn disease patients, including inadequate food intake, decreased assimilation and increased loss of nutrients, and increased energy expenditure. To assess the effect of steroid therapy on body composition, energy expenditure, and fuel selection in Crohn disease, we compared 12 patients (6 men and 6 women) with biopsy-proven ileal Crohn disease with 11 healthy volunteers (6 men and 5 women). Five patients [Crohn's disease activity index (CDAI) = 98.4 +/- 3.78] took no medication and seven patients (CDAI = 283.9 +/- 22.5) were administered 29 +/- 18 mg prednisone/d. Body composition was evaluated by isotopic dilution and bioelectrical impedance analysis, and 24-h energy expenditure and basal metabolic rate were measured in a respiratory chamber. Fat-free mass was not significantly different among groups, whereas fat mass was lower in patients than in control subjects. Energy intake was higher in treated patients than in both untreated patients (P = 0.004) and control subjects (P = 0.005). Fecal losses were not significantly different between untreated patients and control subjects, but were higher (and proportional to the CDAI) in treated patients than in control subjects (P = 0.001). Metabolizable energy was not significantly different among groups, whereas energy balance was significantly higher in treated patients than in both control subjects (P = 0.0057) and untreated patients (P = 0.018). Nitrogen balance was mildly negative in treated patients compared with both control subjects and untreated patients, but not significantly so. In conclusion, prednisone treatment in Crohn disease patients stimulates food intake, promoting an overall positive energy balance despite large fecal nutrient losses. C1 Univ Cattolica Sacro Cuore, Ctr Fisiopatol Shock, CNR, Rome, Italy. Univ Cattolica Sacro Cuore, Ctr Fisiopatol Shock, Ist Med Interna, Rome, Italy. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Mingrone, G (reprint author), Univ Cattolica Sacro Cuore, Ist Med Interna & Geriatr, Largo A Gemelli 8, I-00168 Rome, Italy. EM iclcm@rm.unicatt.it NR 35 TC 34 Z9 36 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1998 VL 67 IS 1 BP 118 EP 123 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YQ214 UT WOS:000071362100022 PM 9440385 ER PT J AU Vortmeyer, AO Kingma, DW Fenton, RG Curti, BD Jaffe, ES Duray, PH AF Vortmeyer, AO Kingma, DW Fenton, RG Curti, BD Jaffe, ES Duray, PH TI Hepatobiliary lymphoepithelioma-like carcinoma associated with Epstein-Barr virus SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE lymphoepithelioma; lymphoepithelioma-like carcinoma; Epstein-Barr virus; in situ hybridization ID POLYMERASE CHAIN-REACTION; HODGKINS-DISEASE; SALIVARY-GLANDS; LYMPHOMAS AB We describe the clinical and pathologic features of a lymphoepithelioma-like carcinoma (LELC) that originated in the hepatobiliary system. A woman, aged 71 years, was first seen with a noncholangiolar adenocarcinoma with lymphoid stroma, which was discovered by open liver biopsy in 1993. In 1995, retroperitoneal and peripancreatic lymph nodes were involved by LELC. There currently is no evidence of distant metastasis outside the hepatobiliary peripancreatic region. Review of the biopsy material revealed a well-differentiated adenocarcinoma with transition into LELC. Epstein-Barr virus (EBV) transcripts were expressed in all histologic phases of the tumor by in situ hybridization using immunoalkaline phosphatase-labeled oligonucleotide probes for EBV-encoded RNA I on formalin-fixed, paraffin-embedded sections. Polymerase chain reaction analysis for EBV nuclear antigen 2 was consistent with EBV strain type A. The LMP-I gene was found to be wild type by polymerase chain reaction analysis. To our knowledge, this is the first report of a primary hepatobiliary adenocarcinoma associated with EBV infection that transformed into an undifferentiated LELC. C1 NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, Naval Med Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Duray, PH (reprint author), NIH, Pathol Lab, Bldg 10,Room 2N212,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1998 VL 109 IS 1 BP 90 EP 95 PG 6 WC Pathology SC Pathology GA YN591 UT WOS:000071185200015 PM 9426523 ER PT J AU Ghosh, S AF Ghosh, S TI The search for complex disease genes: Research advances in molecular techniques. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIH, 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 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1998 VL 10 IS 1 MA 124 BP 123 EP 124 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA YU971 UT WOS:000071775500040 ER PT J AU Hanson, RL AF Hanson, RL TI Genetics of type 2 diabetes mellitus in Pima Indians. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIDDK, Phoenix, AZ 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 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1998 VL 10 IS 1 MA 125 BP 124 EP 124 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA YU971 UT WOS:000071775500041 ER PT J AU Hediger, ML Overpeck, MD Maurer, KR Kuczmarski, RJ McGlynn, A Davis, WW AF Hediger, ML Overpeck, MD Maurer, KR Kuczmarski, RJ McGlynn, A Davis, WW TI Growth and fatness of infants and children born small(SGA) or large-for-gestational-age (LGA): findings from the Third National Health and Nutrition Examination Survey (NHANES III). SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NCHS, Hyattsville, MD USA. Klemm Anal Grp, Hyattsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1998 VL 10 IS 1 MA 128 BP 125 EP 125 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA YU971 UT WOS:000071775500044 ER PT J AU Moldin, SO AF Moldin, SO TI Genetic analysis of mental disorders. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIMH, NIH, 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 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1998 VL 10 IS 1 MA 146 BP 132 EP 132 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA YU971 UT WOS:000071775500062 ER PT J AU Pearson, JD Kao, SY Brant, LJ Metter, EJ Tockman, MS Fozard, JL AF Pearson, JD Kao, SY Brant, LJ Metter, EJ Tockman, MS Fozard, JL TI Longitudinal change in forced expiratory volume in healthy, non-smoking men and women: The Baltimore longitudinal study of aging SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Human-Biology-Association CY APR, 1995 CL OAKLAND, CALIFORNIA SP Human Biol Assoc ID PULMONARY-FUNCTION; LUNG-FUNCTION; RESPIRATORY SYMPTOMS; VENTILATORY FUNCTION; FOLLOW-UP; DECLINE; RISK; DISEASE; ADULTS; MODELS AB Studies of age-associated changes in forced expiratory volume at one second (FEV1) have varied in the degree of screening for health and smoking, and have not examined age differences in variability in FEV1. Longitudinal rates of change and variability in. FEV1 among healthy lifetime-non-smoking White men and women in the Baltimore Longitudinal Study of Aging (BLSA) are reported. Longitudinal FEV1 data collected at 2-year intervals for up to 28 yr in 91 men (417 observations) and 14 yr in 82 women (248 observations) were modelled using mixed-effects regression models. Longitudinal percentile distributions of FEV were calculated which reflect age differences in between-subjects variability. The results show that longitudinal rate of decline in FEV1 is more rapid in men than women (340 ml/decade in men compared to 240-330 ml/decade in women), hut similar on a percentage basis (10%) and the difference is not statistically significant; FEV1 decline begins in early adulthood and progresses at a relatively constant rate over the adult lifespan; longitudinal decline in FEV1 in BLSA participants is not statistically different from cross-sectional estimates from the BLSA and Crape et al. (1981); and between-subjects variability is greater in men than women and increases with age. The results document a relatively steady progressive longitudinal decline in FEV1 in healthy non-smoking White adults, as well as age and gender differences in variability in FEV1, The percentile distribution curves reported here are apparently the first reference values for FEV1 to be derived using longitudinal methods that reflect age-specific differences in variability. (C) 1998 Wiley-Liss, Inc. C1 NIA, Gerontol Res Ctr, Longitudinal Studies Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Pearson, JD (reprint author), Merck Res Labs, BL2-3,POB 4, W Point, PA 19486 USA. EM Jay_Pearson@Merck.com RI Fozard, James Leonard/B-3660-2009 NR 31 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1998 VL 10 IS 4 BP 471 EP 481 PG 11 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA ZV909 UT WOS:000074353900007 ER PT J AU Byrne, J Rasmussen, SA Steinhorn, SC Connelly, RR Myers, MH Lynch, CF Flannery, J Austin, DF Holmes, FF Holmes, GE Strong, LC Mulvihill, JJ AF Byrne, J Rasmussen, SA Steinhorn, SC Connelly, RR Myers, MH Lynch, CF Flannery, J Austin, DF Holmes, FF Holmes, GE Strong, LC Mulvihill, JJ TI Genetic disease in offspring of long-term survivors of childhood and adolescent cancer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BIRTH-DEFECTS; WILMS-TUMOR; CONGENITAL-ANOMALIES; PREGNANCY; CHILDREN; LEUKEMIA; MALFORMATIONS; RADIATION; EXPOSURE; PREVALENCE AB Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P = .33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P = .43). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells. C1 Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. NCI, Clin Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometry Branch, NIH, Bethesda, MD 20892 USA. Boyne Res Inst, Drogheda, Ireland. Univ Florida, Dept Pediat, Div Genet, Gainesville, FL USA. Dept Hlth Serv, Calif Tumor Registry, Emeryville, CA USA. Dept Publ Hlth, Connecticut Tumor Registry, Hartford, CT USA. State Hlth Registry Iowa, Iowa City, IA USA. Univ Texas, MD Anderson Hosp & Tumor Inst, Dept Expt Pediat Genet, Houston, TX USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Univ Kansas, Med Ctr, Dept Pediat, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Prevent Med, Kansas City, KS 66103 USA. Univ Pittsburgh, Dept Genet, Pittsburgh, PA USA. RP Byrne, J (reprint author), Childrens Natl Med Ctr, Dept Hematol Oncol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM jbyrne@cnmc.org NR 41 TC 129 Z9 135 U1 0 U2 2 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 JAN PY 1998 VL 62 IS 1 BP 45 EP 52 DI 10.1086/301677 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YY246 UT WOS:000072127900009 PM 9443870 ER PT J AU Li, LY Drayna, D Hu, D Hayward, A Gahagan, S Pabst, H Cowan, MJ AF Li, LY Drayna, D Hu, D Hayward, A Gahagan, S Pabst, H Cowan, MJ TI The gene for severe combined immunodeficiency disease in Athabascan-speaking native Americans is located on chromosome 10p SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID V(D)J RECOMBINATION; DNA-REPAIR; HUMAN GENOME; LINKAGE; INTERLEUKIN-7; LOCALIZATION; MUTATION; KINASE; MICE; MAP AB Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T-B- SCID, is inherited as an autosomal recessive trait and is characterized by a profound deficiency of both T cell and B cell immunity. There is a uniquely high frequency of T-B- SCID among Athabascan-speaking Native Americans (A-SCID). To localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of similar to 300 microsatellite markers in 14 affected Athabascan-speaking Native American families. We obtained conclusive evidence for linkage of the A-SCID locus to markers on chromosome 10p. The maximum pairwise LOD scores 4.53 and 4.60 were obtained from two adjacent markers, D10S191 and D10S1653, respectively, at a recombination fraction of theta = .00. Recombination events placed the gene in an interval of similar to 6.5 cM flanked by D10S1664 and D10S674. Multipoint analysis positioned the gene for the A-SCID phenotype between D10S191 and D10S1653, with a peak LOD score of 5.10 at D10S191. Strong linkage disequilibrium was found in five linked markers spanning similar to 6.5 cM in the candidate region, suggesting a founder effect with an ancestral mutation that occurred sometime before 1300 A.D. C1 Univ Calif San Francisco, Dept Pediat, Bone Marrow Transplant Div, San Francisco, CA 94143 USA. Natl Inst Deafness & Commun Disorders, NIH, Rockville, MD USA. Tuba City Indian Hlth Serv, Dept Pediat, Tuba City, AZ USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Alberta, Dept Pediat, Edmonton, AB, Canada. RP Cowan, MJ (reprint author), Univ Calif San Francisco, Dept Pediat, Bone Marrow Transplant Div, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM mcowan@peds.ucsf.edu FU NIAID NIH HHS [AI28339] NR 42 TC 29 Z9 29 U1 0 U2 1 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 JAN PY 1998 VL 62 IS 1 BP 136 EP 144 DI 10.1086/301688 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA YY246 UT WOS:000072127900019 PM 9443881 ER PT J AU Blair, A Cantor, KP Zahm, SH AF Blair, A Cantor, KP Zahm, SH TI Non-Hodgkin's lymphoma and agricultural use of the insecticide lindane SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE cancer; agriculture; farmers; insecticides; non-Hodgkin's lymphoma; epidemiology; pesticides; lindane ID PESTICIDE USE; PROXY RESPONDENTS; RISK-FACTORS; MINNESOTA; IOWA; MEN AB Data from population-based case-control studies of non-Hodgkin's lymphoma among white men from Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate potential risks from environmental exposures in more detail, while controlling for potential confounding factors. These data provided the opportunity to evaluate the risk of non-Hodgkin's lymphoma from potential exposures to lindane, a pesticide that causes cancer in laboratory animals and has been associated with human cancer in a few epidemiologic investigations. This pooled data set includes 987 individuals with non-Hodgkin's lymphoma and 2,895 population-based controls. Information was obtained by telephone or in person interviews, which included detailed questions on farm practices and agricultural use of chemicals. Logistic regression was used to calculate odds ratios (ORs) adjusted for age, state of residence, and subject or proxy interviews. Reported use of lindane significantly increased the risk of non-Hodgkin's's lymphoma by 50%. Some use characteristics were suggestive of an association. ORs were greater among persons who first used the pesticide 20 years before diagnosis (OR = 1.7) than more recently (OR = 1.3), among those who reported more frequent use (OR = 2.0 for use 5 or more days per year versus 1.6 for fewer than five days per year), and from use on crops (OR = 1.9), rather than from use on animals (OR = 1.3), although these differences were not statistically significant. On the other hand, ORs were lower when based on direct interviews (OR = 1.3) than on data from proxy respondents (OR = 2.1) and adjustment for potential confounding by use of 2,4-D and diazinon reduced the ORs associated with lindane use from 1.5 to 1.2 and 1.3, respectively. Lindane does not appear to be a major etiologic factor in the development of non-Hodgkin's's lymphoma, although a small role cannot be ruled out. (C) 1998 Wiley-Liss, Inc. RP Blair, A (reprint author), NCI,OCCUPAT EPIDEMIOL BRANCH,EPN ROOM 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 19 TC 41 Z9 42 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1998 VL 33 IS 1 BP 82 EP 87 DI 10.1002/(SICI)1097-0274(199801)33:1<82::AID-AJIM9>3.0.CO;2-Y PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YJ480 UT WOS:A1998YJ48000009 PM 9408531 ER PT J AU Petrella, JR DeCarli, C Dagli, M Grandin, CB Duyn, JH Frank, JA Hoffman, EA Theodore, WH AF Petrella, JR DeCarli, C Dagli, M Grandin, CB Duyn, JH Frank, JA Hoffman, EA Theodore, WH TI Age-related vasodilatory response to acetazolamide challenge in healthy adults: A dynamic contrast-enhanced MR study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Neuroradiology CY MAY, 1997 CL TORONTO, CANADA SP Amer Soc Neuroradiol ID CEREBRAL BLOOD-VOLUME; CEREBROVASCULAR RESERVE CAPACITY; OXYGEN-CONSUMPTION; NORMAL VALUES; RAT-BRAIN; FLOW; STIMULATION; TOMOGRAPHY; PERFUSION; DISEASE AB PURPOSE: We examined age-related changes in baseline regional cerebral blood volume (rCBV) and response to acetazolamide stimulation by using dynamic contrast-enhanced MR imaging. METHODS: Thirty healthy volunteers ranging widely in age (23 to 82 years) were examined before and after intravenous injection of acetazolamide with dynamic susceptibility contrast-enhanced MR imaging. rCBV values were normalized for intersubject and intrasubject comparison by estimating an arterial input function directly from the imaging data. Preacetazolamide baseline rCBV and the percentage volume change index (PVCI) of the postacetazolamide to preacetazolamide state were calculated and examined as a function of age. RESULTS: Older adults (>50 years) had lower baseline rCBV per unit tissue than did younger adults (<50 years), but higher rCBV after acetazolamide stimulation, Baseline rCBV tended to decrease with age in the medial frontal and frontoparietal gray matter regions. Response to acetazolamide stimulation, measured by PVCI, showed a significant age-related increase in gray matter, approximately 0.5% per year. CONCLUSION: rCBV can be significantly increased after acetazolamide stimulation in the healthy aged. These results support the notion that age-related decreases in rCBV measured at rest reflect reduced regional metabolic requirements rather than reduced capacity for regional substrate delivery. These data serve as a normative baseline for comparison studies of rCBV vascular reserve in aging persons with various cerebrovascular disorders. C1 NINDS, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, In Vivo NMR Res Ctr, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Petrella, JR (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA. RI DeCarli, Charles/B-5541-2009; Duyn, Jozef/F-2483-2010 NR 28 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 1998 VL 19 IS 1 BP 39 EP 44 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YM086 UT WOS:000071026700014 PM 9432155 ER PT J AU Grether, JK Hoogstrate, J Selvin, S Nelson, KB AF Grether, JK Hoogstrate, J Selvin, S Nelson, KB TI Magnesium sulfate tocolysis and risk of neonatal death SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE magnesium and neonatal death; magnesium sulfate tocolysis ID PRETERM LABOR; PREMATURE LABOR; CEREBRAL-PALSY; BIRTH; PREVENTION; MANAGEMENT; INFECTION; CYTOKINES; EFFICACY AB OBJECTIVE: Our purpose was to evaluate the association between in utero exposure to magnesium sulfate and neonatal death. STUDY DESIGN: Case-control comparison was performed of singleton infants who died at 0 to 28 days and control infants who survived to age 3 years and did not have disabling cerebral palsy. All subjects were born between 1983 and 1985 to mothers resident in one of four northern California counties. RESULTS: Magnesium sulfate tocolysis was associated with a decreased risk of neonatal mortality (odds ratio 0.25, 95% confidence interval 0.6 to 1.1). Adjustment for birth weight and gestational age increased the inverse association (odds ratio 0.09, 95% confidence interval 0.01 to 0.93). The association between neonatal mortality and magnesium sulfate was not altered by maternal infection, gender, maternal race or ethnicity, maternal age, level of care, breech presentation, surgical delivery, corticosteroids, abruptio placentae, placenta previa, or bleeding on admission. CONCLUSIONS: Magnesium sulfate tocolysis was not associated with increased neonatal mortality in premature infants. Thus any association of magnesium with reduced long-term neurologic morbidity is unlikely to be the result of selective mortality of vulnerable infants. C1 Calif Dept Hlth Serv, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Biostat & Informat Sci, Berkeley, CA 94720 USA. NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Grether, JK (reprint author), Calif Dept Hlth Serv, Calif Birth Defects Monitoring Program, 1900 Powell St,Suite 1050, Emeryville, CA 94608 USA. NR 29 TC 51 Z9 51 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1998 VL 178 IS 1 BP 1 EP 6 DI 10.1016/S0002-9378(98)70617-9 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YU977 UT WOS:000071776100001 PM 9465794 ER PT J AU Natchiar, GN Thulasiraj, RD Negrel, AD Bangdiwala, S Rahmathallah, R Prajna, NV Ellwein, LB Kupfer, C AF Natchiar, GN Thulasiraj, RD Negrel, AD Bangdiwala, S Rahmathallah, R Prajna, NV Ellwein, LB Kupfer, C TI The Madurai Intraocular Lens Study - I: A randomized clinical trial comparing complications and vision outcomes of intracapsular cataract extraction and extracapsular cataract extraction with posterior chamber intraocular lens SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: The Madurai Intraocular Lens Study (MIOLS) was designed to compare safety, efficacy, and quality of life outcomes after either intracapsular cataract extraction with aphakic glasses (ICCE-AG) or extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL). METHODS: The Madurai Intraocular Lens Study was a nonmasked randomized controlled clinical trial conducted at a single hospital. Thirty four hundred patients with age-related cataracts and having a best corrected visual acuity less than or equal to 20/120 in the better eye were randomly assigned to either of the two cataract operative procedures. The main clinical outcomes were safety (complication rates) and efficacy (best-corrected visual acuity at 1 year equal to or better than 20/40). In addition, a subset of 1,700 trial participants received questionnaires before surgery, at 6 months after surgery, and at 1 year after surgery to measure visual functioning and vision related quality of life. RESULTS: Details of study design, study organization, clinical and quality of life outcome variables, sample size calculations, patient eligibility criteria and recruitment, randomization and masking, participant flow, adherence to follow-up, quality assurance, and statistical methods are presented. CONCLUSIONS: The Madurai Intraocular Lens Study has sufficient power to detect clinically significant differences between the treatment options. There were no statistically significant differences between the two treatment groups for any of the major study variables at baseline. A high level of quality assurance was maintained throughout the October 1993 to June 1996 study period. The results should be applicable to all settings where the requisite expertise and resources are present. C1 NEI, Bethesda, MD 20892 USA. Aravind Eye Hosp & Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India. WHO, Prevent Blindness Program, CH-1211 Geneva, Switzerland. Univ N Carolina, Chapel Hill, NC USA. Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India. RP Kupfer, C (reprint author), NEI, 31 Dr,MSC 2510,Bldg 31,Room 6A-03, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 14 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 1998 VL 125 IS 1 BP 1 EP 13 DI 10.1016/S0002-9394(99)80229-3 PG 13 WC Ophthalmology SC Ophthalmology GA YQ081 UT WOS:000071346100001 PM 9437308 ER PT J AU Prajna , NV Chandrakanth, KS Kim, R Narendran, V Selvakumar, S Rohini, G Manoharan, N Bangdiwala, SI Ellwein, LB Kupfer, C AF Prajna , NV Chandrakanth, KS Kim, R Narendran, V Selvakumar, S Rohini, G Manoharan, N Bangdiwala, SI Ellwein, LB Kupfer, C TI The Madurai Intraocular Lens Study - II: Clinical outcomes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; DEVELOPING-COUNTRIES; IMPLANTATION AB PURPOSE: To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. RESULTS: At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE AG group and 7.7% in the ECCE group (P < .001). Best corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001). CONCLUSION: Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE AG in terms of both visual acuity restoration and safety. C1 Aravind Eye Hosp, Madurai, Tamil Nadu, India. Univ N Carolina, Chapel Hill, NC USA. Postgrad Inst Ophthalmol, Madurai, Tamil Nadu, India. RP Kupfer, C (reprint author), NEI, 31 Ctr Dr,MSC 2510,Bldg 31,Room 6A-03, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 14 TC 70 Z9 72 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 1998 VL 125 IS 1 BP 14 EP 25 DI 10.1016/S0002-9394(99)80230-X PG 12 WC Ophthalmology SC Ophthalmology GA YQ081 UT WOS:000071346100002 PM 9437309 ER PT J AU Fletcher, A Vijaykumar, V Selvaraj, S Thulasiraj, RD Ellwein, LB AF Fletcher, A Vijaykumar, V Selvaraj, S Thulasiraj, RD Ellwein, LB TI The Madurai Intraocular Lens Study - III: Visual functioning and quality of life outcomes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OF-LIFE; CATARACT-SURGERY AB PURPOSE: To compare the effects of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) vs intracapsular cataract extraction with aphakic glasses (ICCE-AG) on everyday visual functioning and quality of life. METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilateral vision-impaired patients, aged 40 to 75 years, with operable cataract were randomly assigned to receive one of the two treatment options. One half in each group were randomly selected for interviewer administration of visual functioning and quality of life questionnaires before surgery and at 6 and 12 months after surgery. RESULTS: Both ICCE-AG and ECCE/PC-IOL produced dramatic improvements in visual functioning and quality of life scores. Patients receiving ECCE/PC-IOL reported larger beneficial changes than did those receiving ICCE-AG, compatible with additional beneficial effects of a moderate magnitude for visual functioning and of a smaller beneficial magnitude for quality of life. All between group differences were highly statistically significant (P < .00001). The additional benefits of ECCE/PC-IOL are not explained by visual acuity differences. A higher proportion of patients in the ICCE-AG group reported problems on a vision problem checklist at 6 months (more than 50%) than did patients in the ECCE/PC-IOL group (approximately 30%). CONCLUSIONS: In this developing-country setting, ICCE-AG and ECCE/PC-IOL were associated with substantial benefits in improved everyday vision function and vision related quality of life. Patients who received ECCE/PC-IOL reported greater benefits and fewer problems with vision than did patients who received ICCE-AG. C1 Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Sci, London WC1E 7HT, England. Aravind Hosp, Madurai, Tamil Nadu, India. NEI, Bethesda, MD 20892 USA. RP Fletcher, A (reprint author), Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Sci, Keppel St, London WC1E 7HT, England. FU NEI NIH HHS [N01-EY-2103] NR 11 TC 61 Z9 72 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 1998 VL 125 IS 1 BP 26 EP 35 DI 10.1016/S0002-9394(99)80231-1 PG 10 WC Ophthalmology SC Ophthalmology GA YQ081 UT WOS:000071346100003 PM 9437310 ER PT J AU Koivisto, P Kolmer, M Visakorpi, T Kallioniemi, OP AF Koivisto, P Kolmer, M Visakorpi, T Kallioniemi, OP TI Androgen receptor gene and hormonal therapy failure of prostate cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID EPIDERMAL GROWTH-FACTOR; CHROMOSOMAL LOCALIZATION; ANTIANDROGEN WITHDRAWAL; CODON-877 MUTATION; MALIGNANT PROSTATE; C-JUN; TUMORS; EXPRESSION; CARCINOMA; PROGRESSION AB Androgen receptor (AR) is a nuclear transcription factor that binds male sex steroids and mediates the biological effects of these hormones to the target cells, such as the epithelial cells of the prostate gland, by activating transcription of androgen-dependent genes. Withdrawal of androgens or the peripheral blockade of androgen action remain the critical therapeutic options for the treatment of advanced prostate cancer. However, after initial regression, many prostate cancers become hormone refractory and progress further with eventual fatal outcome, Understanding the mechanisms of tumor progression and endocrine therapy failure is an important goal, A large number of different molecular mechanisms may be responsible for development of hormone-refractory recurrent tumors, Many of these involve the AR gene and its complex downstream signaling pathways, The role of AR mutations and altered transactivational properties of the receptor have received the most attention as causative factors for progression. However, other mechanisms, such as AR gene amplification and overexpression or increased local bioconversion of androgens, may contribute to the development of progression by mechanisms that involve androgen-dependent cell growth. Here we review the role of the AR gene and its putative downstream effector pathways during human prostate cancer progression and endocrine therapy failure. C1 Tampere Univ Hosp, Dept Clin Chem, Canc Genet Lab, FIN-33521 Tampere, Finland. Tampere Univ Hosp, Inst Med Technol, FIN-33521 Tampere, Finland. NHGRI, Canc Genet Lab, NIH, Bethesda, MD USA. RP Koivisto, P (reprint author), Tampere Univ Hosp, Dept Clin Chem, Canc Genet Lab, POB 2000, FIN-33521 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 77 TC 145 Z9 155 U1 1 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1998 VL 152 IS 1 BP 1 EP 9 PG 9 WC Pathology SC Pathology GA YQ933 UT WOS:000071439200001 PM 9422516 ER PT J AU Kitada, S Krajewska, M Zhang, X Scudiero, D Zapata, JM Wang, HG Shabaik, A Tudor, G Krajewski, S Myers, TG Johnson, GS Sausville, EA Reed, JC AF Kitada, S Krajewska, M Zhang, X Scudiero, D Zapata, JM Wang, HG Shabaik, A Tudor, G Krajewski, S Myers, TG Johnson, GS Sausville, EA Reed, JC TI Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IN-VIVO PATTERNS; IMMUNOHISTOCHEMICAL ANALYSIS; DEATH AB The BAD protein is a pro-apoptotic member of the Bcl-2 family whose ability to heterodimerize with survival proteins such as Bcl-X-L and to promote cell death is inhibited by phosphorylation. Monoclonal antibodies were generated against the human BAD protein and used to evaluate its expression by immunoblotting and immunohistochemistry in normal human tissues and by immunoblot analysis of the National Cancer Institute anti-cancer drug screening panel of 60 human tumor cell lines. BAD protein was detectable by immunoblotting in many normal tissues, with testis, breast, colon, and spleen being among those with the highest steady-state levels. Immunostaining of tissues revealed many examples of cell-type-specific expression of BAD, suggesting dynamic regulation of BAD protein levels in vivo, In many types of normal cells, BAD immunoreactivity was associated with cytosolic organelles resembling mitochondria, suggesting that BAD is often heterodimerized with other Bcl-2 family proteins in vivo, The relative levels of BAD protein varied widely among established human tumor cell lines, with colon, lung, and melanomas generally having the highest expression. As a group, hematopoietic and lymphoid lines contained the least BAD protein. The BAD protein derived from 11 of 41 tumor Lines that expressed this pro-apoptotic protein migrated in gels as a clear doublet, consistent with the presence of hyperphosphorylated BAD protein, Taken together, these findings define for the fit st time the normal cell-type-specific patterns of expression and intracellular locations of the BAD protein in vivo and provide insights into the regulation of this pro-apoptotic Bcl-2 family protein in human tumors. C1 Burnham Inst, Canc Res Ctr, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Reed, JC (reprint author), Burnham Inst, Canc Res Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Zapata, Juan/J-6304-2014; Wang, Hong-Gang/A-3018-2015; OI Zapata, Juan/0000-0002-0110-0009; Shabaik, Ahmed/0000-0003-1987-3453 FU NCI NIH HHS [CA55164] NR 15 TC 97 Z9 99 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1998 VL 152 IS 1 BP 51 EP 61 PG 11 WC Pathology SC Pathology GA YQ933 UT WOS:000071439200008 PM 9422523 ER PT J AU Kimberlin, DF Hauth, JC Goldenberg, RL Bottoms, SF Iams, JD Mercer, B MacPherson, C Thurnau, GR AF Kimberlin, DF Hauth, JC Goldenberg, RL Bottoms, SF Iams, JD Mercer, B MacPherson, C Thurnau, GR TI The effect of maternal magnesium sulfate treatment on neonatal morbidity in <= 1000-gram infants SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE magnesium sulfate; extremely low birth weight ID LOW-BIRTH-WEIGHT; CEREBRAL-PALSY; ULTRASOUND APPEARANCE; PRETERM INFANTS; SCHOOL-AGE; CHILDREN; GRAMS; SURVIVAL; OUTCOMES; HEALTH AB We evaluated the effect of maternal magnesium sulfate treatment on selected neonatal outcomes in less than or equal to 1000-g infants. In a 1-year (1992-1993) observational study, the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units collected outcome data for 799 infants whose birth weights were less than or equal to 1000 g. Only singleton infants, with a gestational age > 20 weeks who were not the product of an induced abortion were included. Our analysis was further limited to those infants without major congenital anomalies, who were deemed potentially viable by the obstetrician, whose mother would have undergone a cesarean delivery for fetal indications, and who survived greater than 2 days. Outcomes were compared in infants whose mothers did and did not receive magnesium sulfate for labor tocolysis. Among the 124 women who did and the 184 who did not receive magnesium sulfate tocolytic therapy, the frequencies of grade III or IV intraventricular hemorrhage (16 vs. 20%, p = 0.34), seizure activity (7 vs. 10%, p = 0.35), grade III or IV retinopathy of prematurity (21 vs. 18% p = 0.59), abnormal neurological exam (28 vs. 28%, p = 0.91), intact survival to 120 days or to discharge (48 vs. 44%, p = 0.54), and infant mortality (23 vs. 31%, p = 0.10) were similar. Multiple logistic regression analysis was used to control for the effect of potential confounders (specifically, gestational age) and confirmed the lack of a significant association between maternal magnesium sulfate treatment for tocolysis and selected neonatal outcomes in this population of less than or equal to 1000-gram infants. C1 Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35233 USA. NICHD, Network Maternal Fetal Med Unit, Rockville, MD USA. RP Kimberlin, DF (reprint author), Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, 618 S 20th St,Room OHB 450, Birmingham, AL 35233 USA. NR 29 TC 13 Z9 15 U1 1 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PY 1998 VL 15 IS 11 BP 635 EP 641 DI 10.1055/s-2007-994082 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 169BY UT WOS:000078728700007 PM 10064205 ER PT J AU Bonner, JC Lindroos, PM Rice, AB Moomaw, CR Morgan, DL AF Bonner, JC Lindroos, PM Rice, AB Moomaw, CR Morgan, DL TI Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung fibrosis; vanadium pentoxide; platelet-derived growth factor-receptor system; interleukin-1; transforming growth factor-beta 1 ID MESSENGER-RNA EXPRESSION; GROWTH-FACTOR; LUNG FIBROBLASTS; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNAL TRANSDUCTION; GENE-EXPRESSION; FIBROSIS; INJURY; MACROPHAGES; ISOFORMS AB Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-R alpha is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-R alpha protein by 48 h, and immunohistochemical analysis localized PDGF-R alpha primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-R alpha in vivo preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2P5 in vitro released upregulatory activity for PDGF-R alpha on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1 beta-mediated induction of PDGF-R alpha in vivo is important to lung myofibroblast hyperplasia during fibrogenesis. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 53 Z9 53 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 1998 VL 274 IS 1 BP L72 EP L80 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA YT173 UT WOS:000071572600010 PM 9458803 ER PT J AU Miller, DS AF Miller, DS TI Protein kinase C regulation of organic anion transport in renal proximal tubule SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE confocal microscopy; 3-[1-(3-aminopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)pyrrole-2,5-dione hydrochloride; fluorescence microscopy; killifish; phorbol ester; renal secretion; teleost fish ID P-AMINOHIPPURATE; SECRETION; MECHANISMS; CATIONS; SODIUM; RATS AB Fluorescence microscopy and digital image analysis were used to examine the role of protein kinase C (PKC) in the control of organic anion (fluorescein, FL) transport in killifish renal proximal tubules. Phorbol ester (1-100 nM) reduced cellular and luminal accumulation of FL, and protein kinase inhibitors [staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 10-1,000 nM] increased cellular and luminal accumulation. Phorbol ester effects were blocked by staurosporine. The increases in tissue fluorescence caused by staurosporine were blacked by p-aminohippurate, indicating that they represent increased FL transport on the organic anion system. Neither phorbol ester nor staurosporine had any effects on the cell-to-lumen transport of a fluorescent organic anion that was generated intracellularly from a nonfluorescent, uncharged precursor. Finally studies with a fluorescent PKC inhibitor showed that phorbol ester caused PKC translocation from cytoplasm to the plasma membrane. Together, these findings indicate that renal organic anion transport is negatively correlated with PKC activity and that PKC directly or indirectly controls the basolateral step in transport. C1 NIEHS, Lab Pharmacol & Chem, Intracellular Regulat Sect, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, Intracellular Regulat Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 27 TC 50 Z9 52 U1 0 U2 0 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 JAN PY 1998 VL 274 IS 1 BP F156 EP F164 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YR534 UT WOS:000071504900019 PM 9458835 ER PT J AU Epps, RP Manley, MW Husten, CG Houston, TP Martin, LR Glynn, TJ AF Epps, RP Manley, MW Husten, CG Houston, TP Martin, LR Glynn, TJ TI Transfer of preventive health programs to physicians' practices through medical organizations SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE training, education, medical, continuing; information dissemination; medical research; preventive medicine; training of trainers ID PRIMARY-CARE PHYSICIANS; SMOKING CESSATION; CONTINUING-EDUCATION; TRAINING PHYSICIANS; RANDOMIZED TRIAL; CANCER CONTROL; INFORMATION; SMOKERS; QUIT; INTERVENTION AB Background: Transferring new information to practicing physicians is a complex and often faulty process. Effective transfer is a challenging goal that requires a strategy for reaching large numbers of physicians throughout the country in a short time. However, methods for disseminating preventive health techniques such as smoking cessation have not been well organized. Smoking is the single most important preventable cause of premature mortality, so dissemination of research-based smoking-cessation techniques to physicians' practices is a priority for the National Cancer Institute (NCI). Methods: NCI recruited national, professional medical organizations to collaborate in disseminating smoking-cessation techniques. The goal was to co-sponsor 50 Train-the-Trainer (TT) seminars that would prepare 2,000 professionals as volunteers to instruct their colleagues in smoking-cessation techniques. NCI provided all materials, faculty (nine professionals), advance logistics, CME credits, and followup. The co-sponsor organizations helped develop the training plan, promoted training among their members, enrolled professionals to be trained, and made logistical arrangements for the training sites. Results: During the 4 years of the program, NCI recruited 11 national organizations as co-sponsors; conducted 53 TT seminars in 22 states and Washington, DC; and trained 2,098 professionals as smoking-cessation trainers, who practice nationwide. The many lessons learned provide the basis for recommendations that can assist others who want to work with professional organizations. Conclusion: The National Cancer Institute demonstrated that national organizations of medical professionals can help to disseminate effectively a research-based smoking-cessation program. Twelve recommendations are presented to help others disseminate preventive health techniques nationwide. C1 NCI, DCPC, CCRP, PHAB,NIH,EPN241, Bethesda, MD 20892 USA. RP Epps, RP (reprint author), NCI, DCPC, CCRP, PHAB,NIH,EPN241, 6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. NR 46 TC 5 Z9 5 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 1998 VL 14 IS 1 BP 25 EP 30 DI 10.1016/S0749-3797(97)00011-1 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA YU620 UT WOS:000071736500004 PM 9476833 ER PT J AU Shannon, C Champoux, M Suomi, SJ AF Shannon, C Champoux, M Suomi, SJ TI Rearing condition and plasma cortisol in rhesus monkey infants SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE cortisol; infant; rearing condition ID ATTACHMENT; SURROGATE; STRESS AB Previous studies comparing plasma cortisol levels in mother-reared and nursery-reared rhesus monkey infants under baseline and stress conditions have reported conflicting findings. Differences in subject age, procedures, and specific rearing history may account for many of the discrepant findings. In the present study, mother-reared infants from large social groups, peer-only reared animals, and infants reared with surrogates and limited peer contact were studied in different test conditions across the first 6 months of life. Infants were sampled under three conditions: following a neonatal assessment at Days 14 and 30, immediately upon capture on Day 60, and after 30-min isolation periods on Days 90, 120, and 150. Mother-reared infants exhibited higher cortisol levels on Days 14 and 30 than did both types of nursery-reared infants. In addition, Day 60 basal values of mother-reared infants were higher than those of both peer-reared and surrogate/peer-reared infants. However, on Days 90, 120, and 150, both mother-reared and peer-reared infants exhibited higher cortisol levels in response to separation and 30-min isolation than did the surrogate/peer-reared infants. These differences may reflect group-specific variations in physical environment, capture time, feeding regimen, or diurnal HPA axis rhythms. Am. J. Primatol. 46:311-321, 1998. (C) 1998 Wiley-Liss, Inc. C1 NICHD, Comparat Ethol Lab, Poolesville, MD USA. RP Champoux, M (reprint author), NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 22 TC 101 Z9 101 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1998 VL 46 IS 4 BP 311 EP 321 DI 10.1002/(SICI)1098-2345(1998)46:4<311::AID-AJP3>3.0.CO;2-L PG 11 WC Zoology SC Zoology GA 140BZ UT WOS:000077068000003 PM 9839904 ER PT J AU Byrne, G Suomi, SJ AF Byrne, G Suomi, SJ TI Relationship of early infant state measures to behavior over the first year of life in the tufted capuchin monkey (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE Cebus, capuchin; activity; infant; development; behavior ID MOTOR-ACTIVITY; TEMPERAMENT; ORGANIZATION; STRESS AB Data on activity states were collected from 29 group-housed capuchin monkey (Cebus apella) infants for 3 h each week from birth to 11 weeks of age. The amounts of time spent in sleeping/drowsy, alert-quiet, and alert-active states were measured in these subjects. Videotaped observations of these infants were recorded 3 times/week in the home cage over the first year of life and were scored for a number of social and exploratory behaviors. The extent to which early infant activity state scores predicted later behavior in the home cage was examined. Infant state measures correlated significantly with home cage behavior during months 2-6 in that infants that had been more active in early infancy spent more time alone, with other animals, and in exploration and play and less time with mothers than did quieter infants. Early state measures were less successful in predicting home cage scores beyond 8 months of age, whereas differences in behavior attributable to housing variables became more salient in the latter part of the first year. There was also a negative correlation between mother and infant activity in months 2 and 3, in that more sedentary mothers tended to have more active infants. (C) 1998 Wiley-Liss, Inc.dagger. C1 NICHD, Anim Ctr, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Byrne, G (reprint author), NICHD, Anim Ctr, Comparat Ethol Lab, NIH, POB 529, Poolesville, MD 20837 USA. EM byrneg@lce.nichd.nih.gov NR 19 TC 8 Z9 8 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1998 VL 44 IS 1 BP 43 EP 56 PG 14 WC Zoology SC Zoology GA YM248 UT WOS:000071044600004 PM 9444322 ER PT J AU Westergaard, GC Kuhn, HE Suomi, SJ AF Westergaard, GC Kuhn, HE Suomi, SJ TI Effects of upright posture on hand preference for reaching vs. the use of probing tools by tufted capuchins (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE capuchin; Cebus apella; development; laterality; posture; tool use ID CHIMPANZEES PAN-TROGLODYTES; GALAGO-SENEGALENSIS; BIMANUAL TASK; HANDEDNESS; LATERALITY; MONKEYS; ORANGUTANS; GORILLAS; PANISCUS AB This research examined the effects of task (reaching vs. tool use) and posture (quadrupedal vs. bipedal) on hand preference in tufted capuchins (Cebus apella). Regarding direction of hand preference, we found a significant main effect of posture, as the bipedal stance elicited greater use of the right hand than did the quadrupedal stance, and a significant posture x task interaction, as bipedal reaching elicited greater use of the right hand than did other postural and task conditions. Further, we found a significant main effect of task on strength of hand preference, as tool use elicited more consistent use of one hand over the other than did reaching. Our findings indicate that bipedal reaching facilitates a mild right-hand bias in intensely manipulative primates. We speculate that this moderate bias may have been pushed in the direction of nearly exclusive right-hand preference in most humans with the development of complex tool use. (C) 1998 Wiley-Liss, Inc.dagger. C1 NICHHD, Comparat Ethol Lab, Bethesda, MD USA. RP Westergaard, GC (reprint author), Natl Inst Hlth Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 31 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1998 VL 44 IS 2 BP 147 EP 153 DI 10.1002/(SICI)1098-2345(1998)44:2<147::AID-AJP5>3.0.CO;2-W PG 7 WC Zoology SC Zoology GA YU968 UT WOS:000071775200005 PM 9503126 ER PT J AU Kopala, LC Good, KP Torrey, EF Honer, WG AF Kopala, LC Good, KP Torrey, EF Honer, WG TI Olfactory function in monozygotic twins discordant for schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Abnormalities of olfactory identification ability have been proposed as a marker of cerebral dysfunction in schizophrenia. The authors studied the potential role of genetic factors in olfactory dysfunction by assessing monozygotic twins discordant for schizophrenia and marched comparison subjects. Method: The subjects were 12 Pairs of monozygotic twins discordant for schizophrenia and 12 healthy subjects matched for sex and age. Each subject completed the University of Pennsylvania Smell Identification Test. Results: The combined twin group scored significantly lower on smell identification than did the comparison group. The affected and unaffected twin groups did not differ from each other. Conclusions: Genetic factors may contribute to cerebral dysfunction as assessed by olfactory identification ability. C1 Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. NIMH, St Elizabeths Hosp, Ctr Neurosci, Washington, DC 20032 USA. Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. RP Kopala, LC (reprint author), Camp Hill Hosp, Dept Psychiat, Res Off, Suite 4083,Abbie Lane Bldg,5909 Jubilee Rd, Halifax, NS B3H 2E2, Canada. NR 10 TC 36 Z9 36 U1 2 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1998 VL 155 IS 1 BP 134 EP 136 PG 3 WC Psychiatry SC Psychiatry GA YP421 UT WOS:000071275100025 PM 9433354 ER PT J AU Weed, DL AF Weed, DL TI Beyond black box epidemiology SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID PUBLIC-HEALTH; MOLECULAR EPIDEMIOLOGY; FUTURE; 20TH-CENTURY; PARADIGMS; CANCER; ERAS; END C1 NCI, Div Canc Prevent & Control, Prevent Oncol Branch, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), NCI, Div Canc Prevent & Control, Prevent Oncol Branch, EPS-T41,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 30 Z9 32 U1 0 U2 2 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 JAN PY 1998 VL 88 IS 1 BP 12 EP 14 DI 10.2105/AJPH.88.1.12 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP949 UT WOS:000073804800002 PM 9584017 ER PT J AU Rockhill, B Newman, B Weinberg, C AF Rockhill, B Newman, B Weinberg, C TI Use and misuse of population attributable fractions SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID LOW-BIRTH-WEIGHT; RISK-FACTORS; UNITED-STATES; CANCER; BREAST; DEFINITION; PROPORTION; EXPOSURE; DISEASE; ERROR C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Rockhill, B (reprint author), Univ N Carolina, Dept Epidemiol, CB 7400, Chapel Hill, NC 27599 USA. NR 30 TC 785 Z9 794 U1 4 U2 23 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 JAN PY 1998 VL 88 IS 1 BP 15 EP 19 DI 10.2105/AJPH.88.1.15 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP949 UT WOS:000073804800003 PM 9584027 ER PT J AU Thompson, B Rich, LE Lynn, WR Shields, R Corle, DK AF Thompson, B Rich, LE Lynn, WR Shields, R Corle, DK CA COMMIT Res Grp TI A voluntary smokers' registry: Characteristics of joiners and non-joiners in the Community Intervention Trial for Smoking Cessation (COMMIT) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CIGARETTE-SMOKING; PROGRAM; EDUCATION; RISK AB Objectives. This paper examines differences between joiners and nonjoiners of a voluntary smokers' registry. Methods. A baseline prevalence survey was used to identify characteristics of smokers who joined or did not join a smokers' registry. Results. Communities varied significantly in registry enrollment rates. Heavy-smoking joiners expressed more desire to quit, were more likely to live with nonsmokers, and were older than nonjoiners. Light-to-moderate joiners smoked more, were more addicted to cigarettes, and expressed more desire to quit than nonjoiners. Conclusions. Few baseline characteristics differentiated joiners from nonjoiners. Nonjoiners were significantly more likely to achieve cessation than joiners. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Publ Hlth Applicat Res Branch, Bethesda, MD 20892 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. RP Thompson, B (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St,MP-702, Seattle, WA 98104 USA. FU NCI NIH HHS [CN-64100] NR 30 TC 4 Z9 5 U1 0 U2 1 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 JAN PY 1998 VL 88 IS 1 BP 100 EP 103 DI 10.2105/AJPH.88.1.100 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP949 UT WOS:000073804800019 PM 9584012 ER PT J AU Weed, DL AF Weed, DL TI Preventing scientific misconduct SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MEDICAL-RESEARCH; BREAST-CANCER; SCIENCE; INTEGRITY; FRAUD; MISREPRESENTATION; DEFINITION; APPLICANTS; ETHICS; TRIALS C1 NCI, Prevent Oncol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. RP Weed, DL (reprint author), NCI, Prevent Oncol Branch, EPS T-41,6130 Execut Blvd MSC 7105, Bethesda, MD 20892 USA. NR 51 TC 23 Z9 24 U1 0 U2 3 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 JAN PY 1998 VL 88 IS 1 BP 125 EP 129 DI 10.2105/AJPH.88.1.125 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP949 UT WOS:000073804800025 PM 9584019 ER PT J AU Metman, LV Del Dotto, P Blanchet, PJ van den Munckhof, P Chase, TN AF Metman, LV Del Dotto, P Blanchet, PJ van den Munckhof, P Chase, TN TI Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease SO AMINO ACIDS LA English DT Article; Proceedings Paper CT Satellite on Neurobiology at the 5th International Congress on Amino Acids CY AUG 25-29, 1997 CL CHALKIDIKI, GREECE SP Sandoz Res Inst Berne LTD, Berne, Switzerland, Lomberg Chem Fabrik Gmbh, Byk Gulden, Konstanz, Germany, Pfizer Ltd, Kent, England, Pharmacia & Upjohn Co, Kalamazoo, MI, Boehringer Ingelheim, Ingelheim am Rhein, Germany, Merz & Co, Frankfurt am Main, Germany, Astra Arcus AB, Sodertalje, Sweden DE NMDA antagonists; motor response complications ID NMDA RECEPTOR BLOCKADE; BASAL GANGLIA; BRAIN; DEXTROMETHORPHAN; LEVODOPA; PALLIDOTOMY; DISORDERS; REVERSAL; DOPAMINE; CHANNEL AB In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Metman, LV (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 22 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PY 1998 VL 14 IS 1-3 BP 75 EP 82 DI 10.1007/BF01345246 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU287 UT WOS:000071701500014 ER PT J AU Campomenosi, P Assereto, P Bogliolo, M Fronza, G Abbondandolo, A Capasso, A Bellomo, PF Monaco, R Rapallo, A Sciutto, A Orecchia, R Geido, E Giaretti, W AF Campomenosi, P Assereto, P Bogliolo, M Fronza, G Abbondandolo, A Capasso, A Bellomo, PF Monaco, R Rapallo, A Sciutto, A Orecchia, R Geido, E Giaretti, W TI p53 mutations and DNA ploidy in colorectal adenocarcinomas SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID ANEUPLOID CLONAL DIVERGENCE; NONPOLYPOSIS COLON-CANCER; POLYMERASE CHAIN-REACTION; POINT MUTATIONS; GENE; CARCINOMAS; HETEROGENEITY; TUMORIGENESIS; EVOLUTION; SEQUENCE AB The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher's exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis. C1 Natl Canc Inst, CSTA Mutagenesis Lab, Genoa, Italy. Ist Nazl Ric Canc, Lab Biofis & Citometria, I-16132 Genoa, Italy. Univ Genoa, Dept Clin & Expt Oncol, Chair Genet, Genoa, Italy. Cardarelli Hosp, Naples, Italy. RP Giaretti, W (reprint author), Ist Nazl Ric Canc, Lab Biofis & Citometria, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. EM giaretti@hp380.ist.unige.it RI Campomenosi, Paola/C-9729-2011; OI Campomenosi, Paola/0000-0002-8853-1134; Bogliolo, Massimo/0000-0001-8240-7784 NR 43 TC 23 Z9 23 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 1998 VL 17 IS 1 BP 1 EP 12 PG 12 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 128VT UT WOS:000076429600001 PM 9807634 ER PT J AU Adrie, C Hirani, WM Holzmann, A Keefer, L Zapol, WM Hurford, WE AF Adrie, C Hirani, WM Holzmann, A Keefer, L Zapol, WM Hurford, WE TI Selective pulmonary vasodilation by intravenous infusion of an ultrashort half-life nucleophile nitric oxide adduct SO ANESTHESIOLOGY LA English DT Article DE nitric oxide prodrugs; pulmonary hypertension; sheep; sodium nitroprusside ID HYPERTENSION; NITROPRUSSIDE AB Background: PROLI/NO (C5H7/N3O4Na2 . CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenons administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension, Methods; in eight awake healthy sheep with pulmonary Hypertension induced by 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F-2 alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 mu g.kg(-1).min(-1) of SNP or 0.75, 1.5, 3, 6, and 12 mu g.kg(-1).min(-1) of PROLI/NB. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. Results: Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 mu g.kg(-1).min(-1), which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 mu g.kg(-1).min(-1), PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled), Conclusions: The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Hurford, WE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL 42397] NR 15 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1998 VL 88 IS 1 BP 190 EP 195 DI 10.1097/00000542-199801000-00027 PG 6 WC Anesthesiology SC Anesthesiology GA YQ733 UT WOS:000071417800028 PM 9447872 ER PT S AU Malinda, KM Goldstein, AL Grant, DS Kleinman, HK AF Malinda, KM Goldstein, AL Grant, DS Kleinman, HK BE Maragoudakis, ME TI Thymosin beta 4 promotes endothelial cell migration and angiogenesis SO ANGIOGENESIS: MODELS, MODULATORS, AND CLINICAL APPLICATIONS SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES A, LIFE SCIENCES LA English DT Proceedings Paper CT NATO Advanced Study Institute on Angiogenesis - Models, Modulators, and Clinical Applications CY JUN 20-30, 1997 CL RHODES, GREECE SP NATO Sci Affairs Div C1 NIDR, NIH, Bethesda, MD 20892 USA. RP Malinda, KM (reprint author), NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0258-1213 BN 0-306-45833-0 J9 NATO ADV SCI I A-LIF PY 1998 VL 298 BP 157 EP 163 PG 3 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA BK96D UT WOS:000073945800018 ER PT J AU Doppman, JL Oldfield, EH Nieman, LK AF Doppman, JL Oldfield, EH Nieman, LK TI Bilateral sampling of the internal jugular vein to distinguish between mechanisms of adrenocorticotropic hormone-dependent Cushing syndrome SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INFERIOR PETROSAL SINUS; CORTICOTROPIN-RELEASING HORMONE; DIFFERENTIAL-DIAGNOSIS; CAVERNOUS SINUS; ACTH; OVERNIGHT AB Background: Bilateral sampling of the petrosal sinuses to distinguish Cushing disease from the ectopic adrenocorticotropic hormone (ACTH) syndrome is accurate but technically demanding and risky. Bilateral sampling of the internal jugular vein is simpler and safer. Objective: To compare bilateral internal jugular vein sampling with bilateral inferior petrosal sinus sampling for distinguishing patients with Cushing disease from those with the ectopic ACTH syndrome. Setting: Tertiary referral hospital. Patients: 20 patients with surgically proven Cushing disease and 1 patient with proven ectopic ACTH syndrome. Intervention: All patients underwent petrosal sinus sampling and jugular vein sampling before and after administration of corticotropin-releasing hormone (CRH) on separate days. Measurements: Ratios of central ACTH to peripheral ACTH in petrosal sinus samples and jugular vein samples were calculated before and after administration of CRH. Results: Ratios of central to peripheral ACTH were diagnostic for Cushing disease (>2 before administration of CRH and >3 after administration of CRH) in jugular vein samples from 16 of 20 patients with surgically proven Cushing disease (sensitivity, 80% [95% CI, 56% to 96%]). Ten of these 16 patients (63%) had diagnostic results only after CRH was administered. The average ratio of central to peripheral ACTH in jugular vein samples was 2.7 before CRH and 7.7 after CRH. Ratios of central to peripheral ACTH were diagnostic in petrosal sinus samples from 19 of 20 patients with surgically proven Cushing disease (sensitivity, 95% [CI, 75% to 99%]). Samples from all 19 patients had diagnostic ratios before and after administration of CRH. The average ratio of central to peripheral ACTH in petrosal sinus samples was 17.7 before CRH and 90.0 after CRH. In the patient with the ectopic ACTH syndrome, ratios of central to peripheral ACTH were negative in jugular vein samples and petrosal sinus samples before and after CRH (<2 and <3, respectively). Conclusions: Jugular vein sampling correctly identified ACTH-secreting pituitary adenomas in 80% of patients with proven Cushing disease. Administration of CRH was essential for diagnostic results in 63% of the patients. Jugular vein sampling is less invasive than petrosal sinus sampling. Negative results on jugular vein sampling should be confirmed by petrosal sinus sampling. C1 NINDS, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NINDS, Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Doppman, JL (reprint author), NINDS, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 14 TC 37 Z9 38 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 JAN 1 PY 1998 VL 128 IS 1 BP 33 EP 36 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YN342 UT WOS:000071158000006 PM 9424979 ER PT J AU DeCarli, C Hatta, J Fazilat, S Fazilat, S Gaillard, WD Theodore, WH AF DeCarli, C Hatta, J Fazilat, S Fazilat, S Gaillard, WD Theodore, WH TI Extratemporal atrophy in patients with complex partial seizures of left temporal origin SO ANNALS OF NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; INTRACTABLE PARTIAL EPILEPSY; FOCAL MOTOR SEIZURES; LOBE EPILEPSY; HIPPOCAMPAL-FORMATION; COMPUTED-TOMOGRAPHY; FUNCTIONAL-ANATOMY; METABOLIC ANATOMY; MOSSY FIBERS; BRAIN AB Total cerebral, temporal lobe, hippocampal, caudate, and lenticular nuclei volumes were quantified from magnetic resonance images of 21 patients with left temporal lobe epilepsy and medically intractable complex partial seizures. These regional brain volumes were compared with the same measures in 19 controls. No significant differences in total cerebral, left temporal lobe, right temporal lobe, or total temporal lobe volumes were found. As expected, left hippocampal volumes were significantly smaller in the patients with epilepsy than in control subjects. The left hippo campus-to-right hippocampus volume ratio was significantly lower in patients than in control subjects. In addition to left hippocampal volumes, mean left thalamic, left caudate, and bilateral lenticular volumes were significantly smaller in the patients with epilepsy than in control subjects. The left-to-right thalamic volume ratio was also significantly lower in the patients with epilepsy compared with control subjects, but there were no significant group differences in caudate or lenticular ratios. These results show that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. The pathophysiological significance of our findings is uncertain. They could be related to the underlying cause of the disorder. However, volume loss also may reflect damage due to involvement of these structures in recurrent seizure activity. C1 NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,9000 Rockville Piek, Bethesda, MD 20892 USA. RI DeCarli, Charles/B-5541-2009 NR 40 TC 123 Z9 123 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1998 VL 43 IS 1 BP 41 EP 45 DI 10.1002/ana.410430110 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YR531 UT WOS:000071504600006 PM 9450767 ER PT J AU Zipp, F Weller, M Calabresi, PA Frank, JA Bash, CN Dichgans, J McFarland, HF Martin, R AF Zipp, F Weller, M Calabresi, PA Frank, JA Bash, CN Dichgans, J McFarland, HF Martin, R TI Increased serum levels of soluble CD95 (APO-1/Fas) in relapsing-remitting multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; T-CELLS; APOPTOSIS; SYSTEM; BLOOD; BRAIN AB CD95/CD35 ligand interactions are critically involved in the negative regulation of peripheral T-cell responses. Here, we report that serum levels of soluble CD95 are significantly elevated in patients with relapsing remitting multiple sclerosis. In a transectional study, CD95 levels did not correlate with clinical disability or lesion formation on magnetic resonance imaging. Longitudinally, Expanded Disability Status Scale changes were associated with high CD95 levels. Interferon-beta (IFN beta) treatment led to an initial increase and subsequent decline of serum CD95 levels. Interestingly, patients generating neutralizing antibodies to the drug had significantly higher baseline CD95 levels before IFN beta treatment than those without neutralizing antibodies. C1 Univ Tubingen, Dept Neurol, D-72076 Tubingen, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Zipp, F (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI Zipp, Frauke/C-9968-2015 OI Zipp, Frauke/0000-0002-1231-1928 NR 19 TC 65 Z9 66 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1998 VL 43 IS 1 BP 116 EP 120 DI 10.1002/ana.410430120 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YR531 UT WOS:000071504600016 PM 9450777 ER PT J AU Houghten, R Appel, J Johnson, J Narayanan, V Pinilla, C Wilson, D Pines, T AF Houghten, R Appel, J Johnson, J Narayanan, V Pinilla, C Wilson, D Pines, T TI The effectiveness of mixture-based synthetic combinatorial libraries for the identification of novel anti-cancer agents SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Inst Mol Studies, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 005 BP 2 EP 2 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600009 ER PT J AU Arbuck, SG Ivy, P Setser, A Eisenhauer, E Wanders, J AF Arbuck, SG Ivy, P Setser, A Eisenhauer, E Wanders, J CA Common Toxicity Criteria Rev Comm TI Common toxicity criteria (CTC) version 2.0: Highlights and tools SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Common Toxic Criteria Review Comm, Bethesda, MD 20892 USA. EORTC, Amsterdam, Netherlands. NCI Canada, Kingston, ON, Canada. NR 0 TC 1 Z9 1 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 035 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600038 ER PT J AU Takimoto, CH Morrison, G Guemei, A Band, RA Cottrell, J Monahan, BP Arbuck, SG Chen, A Hamilton, JM Allegra, CJ Grem, JL AF Takimoto, CH Morrison, G Guemei, A Band, RA Cottrell, J Monahan, BP Arbuck, SG Chen, A Hamilton, JM Allegra, CJ Grem, JL TI A phase I and pharmacologic study of irinotecan administered as a 96 hr infusion weekly for two consecutive weeks to adult cancer patients SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 041 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600044 ER PT J AU Sausville, EA Headlee, D Stinson, SF Lush, RM Figg, WD Arbuck, SG Senderowicz, AM AF Sausville, EA Headlee, D Stinson, SF Lush, RM Figg, WD Arbuck, SG Senderowicz, AM TI Cyclin-dependent kinases: Targets for novel therapeutic approaches SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 050 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600053 ER PT J AU Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK AF Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK TI World Health Organization Classification of lymphomas: A work in progress SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE B cell; Hodgkin's disease; leukemia; lymphoma; non-Hodgkin's lymphoma; T cell ID T-CELL LYMPHOMA; MONOCLONAL-ANTIBODY ALK1; NON-HODGKINS-LYMPHOMAS; LYMPHOPROLIFERATIVE DISORDERS; CLINICOPATHOLOGICAL ENTITY; CLINICAL-SIGNIFICANCE; TRANSLOCATION; PHENOTYPE; NEOPLASMS; PROPOSAL AB The World Health Organization (WHO) publishes classification handbooks for all neoplastic diseases. The last WHO Classification of leukemias and lymphomas was published in 1976, Since that time, through cytogenetics and molecular biology it has been shown that many hematopoietic neoplasms are associated with a unique genetic profile. Similarly, the development of widely available and routinely applied monoclonal antibodies has allowed the identification of a unique immunophenotypic profile for most leukemias and lymphomas. These techniques have permitted the recognition of a number of distinct disease entities, and also enhance both diagnostic accuracy and reproducibility. The WHO Classification has been developed under the joint auspices of the European Association for Hematopathology (EAHP) and the Society for Hematopathology (SH), First organized in 1995, the Steering Committee appointed 10 committees covering T-cell and B-cell lymphomas and leukemias, myeloid and histiocytic tumors. The committees were asked to develop a list of diseases within their topic area. and to establish definitions of each disease according to established criteria. The WHO Classification uses the principles of the R.E.A.L. Classification. which defines each disease according to its morphology, immunophenotype, genetic features, postulated normal counterpart, and clinical features. Morphologic and clinical variants of individual diseases are discussed in the text, and their use is optional. The proposed classification was presented at the USCAP meeting in 1997, the site of the first joint meeting of the EAHP and SH. The presentation was followed by an open forum attended by EAHP and SH members. The Steering Committee also appointed a Clinical Advisory Committee to ensure that the classification meets clinical needs, and to resolve questions of clinical significance. The proposed WHO Classification for lymphomas is similar to the R.E.A.L. Classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1993. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hotel Dieu, Serv Cent Anat & Cytol Pathol, Paris, France. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,MSC-1500,10 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 51 Z9 52 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 25 EP 30 DI 10.1023/A:1008462124002 PG 6 WC Oncology SC Oncology GA 163AD UT WOS:000078379300005 ER PT J AU Rudiger, T Jaffe, ES Delsol, G deWolf-Peeters, C Gascoyne, RD Georgii, A Harris, NL Kadin, ME MacLennan, KA Poppema, S Stein, H Weiss, LE Muller-Hermelink, HK AF Rudiger, T Jaffe, ES Delsol, G deWolf-Peeters, C Gascoyne, RD Georgii, A Harris, NL Kadin, ME MacLennan, KA Poppema, S Stein, H Weiss, LE Muller-Hermelink, HK TI Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma) SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE differential diagnosis; grey zone; Hodgkin's lymphoma; immunohistochemistry; pathology; workshop report ID REED-STERNBERG CELLS; COMPOSITE LYMPHOMA; T-CELL; B-CELLS; EXPRESSION; CLASSIFICATION; DISORDERS; MARKER; ORIGIN AB Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma? anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified. C1 Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany. NCI, Pathol Lab, Bethesda, MD 20892 USA. CHU Purpan, Toulouse, France. Univ Leuven, Louvain, Belgium. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Med Hsch Hannover, Hannover, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Hosp, Boston, MA 02215 USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. Univ Groningen, NL-9700 AB Groningen, Netherlands. Univ Klinikum Benjamin Franklin, Berlin, Germany. City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Rudiger, T (reprint author), Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Poppema, Sibrand/D-1204-2012 NR 27 TC 40 Z9 41 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 31 EP 38 DI 10.1023/A:1008466208072 PG 8 WC Oncology SC Oncology GA 163AD UT WOS:000078379300006 ER PT J AU Mondin, C von Poser, G Mans, DRA Ferraz, A Diel, CL de Lima, C Lopes, RM Barros, M da Rocha, AB Varella, D Cragg, G Schwartsmann, G AF Mondin, C von Poser, G Mans, DRA Ferraz, A Diel, CL de Lima, C Lopes, RM Barros, M da Rocha, AB Varella, D Cragg, G Schwartsmann, G TI Targeted plant collection as a rational means to acquire candidate anticancer compounds for screening SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 S Amer Off Anticanc Drug Dev, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Pharm, Porto Alegre, RS, Brazil. Colegio Integrado Objet, Brasilia, DF, Brazil. NCI, Nat Prod Branch, Bethesda, MD USA. RI Schwartsmann, Gilberto/G-4256-2016 OI Schwartsmann, Gilberto/0000-0002-7850-1644 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 134 BP 35 EP 35 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600106 ER PT J AU Yancik, R Wesley, MN Ries, LA AF Yancik, R Wesley, MN Ries, LA TI Impact of age and comorbidity on cancer diagnosis, treatment, and outcome in older patients: perspectives from the NIA/NCI SEER study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. Informat Management Sci, Silver Spring, MD USA. NCI, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 3 MA 32 BP 36 EP 37 PG 2 WC Oncology SC Oncology GA 135BG UT WOS:000076779500033 ER PT J AU Vishnuvajjala, R Hollingshead, M Tabibi, E AF Vishnuvajjala, R Hollingshead, M Tabibi, E TI Universal vehicles for in vivo hollow fiber testing SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, DCTD, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 152 BP 39 EP 39 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600124 ER PT J AU Hendriks, HR Burtles, S Radtke, S Schultz, RJ Double, JA Sausville, EA Newell, DR AF Hendriks, HR Burtles, S Radtke, S Schultz, RJ Double, JA Sausville, EA Newell, DR TI Cell-based screening and pharmacological strategies for the selection of new anticancer agents: A collaboration between the National Cancer Institute (NCI), Cancer Research Campaign (CRC) and EORTC SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 EORTC, Amsterdam, Netherlands. CRC, London, England. NCI, Liaison Off, Brussels, Belgium. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 155 BP 40 EP 40 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600127 ER PT J AU Kwak, LW AF Kwak, LW TI Tumor vaccination strategies combined with autologous peripheral stem cell transplantation SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT International Consensus Conference on High-Dose Therapy with Hematopoietic Stem Cell Transplantation in Diffuse Large-Cell Lymphoma CY APR 19-21, 1998 CL LYON, FRANCE DE lymphoma; T-cell immunity; tumor vaccine ID BONE-MARROW TRANSPLANTATION; HUMORAL IMMUNE-SYSTEM; IDIOTYPIC VACCINATION; LYMPHOMA; IMMUNIZATION; RESISTANCE; IMMUNOGLOBULIN; ANTIBODY; GRAFT; DONOR AB Despite advances in high-dose therapy with autologous stem cell transplantation for lymphomas, relapse of the underlying disease remains a significant obstacle. Recent advances in cancer vaccine development, specifically, the molecular identification of novel tumor antigens and understanding of cellular signals delivered by cytokines and costimulatory molecules required for efficient T-cell activation, now make it possible to consider combining active specific immunotherapy with PSCT as a strategy for elimination of minimal residual disease. As a model lymphoma-specific antigen, vaccination with patient-specific: immunoglobulin idiotype has been shown to be therapeutically effective when combined with marrow transplantation in small animal models. These preclinical studies predict the feasibility of immunization of human patients with B-cell malignancies vaccinated with this antigen in the post-transplant setting in ongoing clinical trials, especially for T-cell responses. In the future, other vaccine formulations, based on gene therapy approaches to enhance the immunogenicity of whole lymphoma cells or the identification of novel, defined antigens selectively expressed on lymphoma cells, as well as combined strategies of pre- and post-transplant tumor vaccination are envisioned. C1 NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci, Frederick, MD 21702 USA. RP Kwak, LW (reprint author), NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci, Bldg 567,Room 205, Frederick, MD 21702 USA. NR 36 TC 14 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 1 BP 41 EP 46 DI 10.1023/A:1008252008916 PG 6 WC Oncology SC Oncology GA ZX739 UT WOS:000074550200007 ER PT J AU Gupta, SL Waugh, WN Alkaysi, H Bempong, DK Stella, VJ AF Gupta, SL Waugh, WN Alkaysi, H Bempong, DK Stella, VJ TI Formulation development of phenylthiocarbamate (PTC), NSC 161128 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, DTP, Pharmaceut Res Branch, Bethesda, MD 20892 USA. Univ Kansas, Dept Pharm Chem, Lawrence, KS 66045 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 177 BP 46 EP 46 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600149 ER PT J AU Tabibi, SE Krzyzaniak, J Yalkowsky, S AF Tabibi, SE Krzyzaniak, J Yalkowsky, S TI Development of a micro-dispersed parenteral formulation of 17-AAG (NSC-330507) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Pharmaceut Resouces Branch, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 176 BP 46 EP 46 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600148 ER PT J AU Gupta, SL Gupta, S Anderson, B Schlom, J AF Gupta, SL Gupta, S Anderson, B Schlom, J TI Formulation development of point-mutated p21 ras-derived synthetic peptides SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Pharmaceut Resources Branch, DTP, Bethesda, MD 20892 USA. Univ Utah, Dept Pharmaceut Chem, Salt Lake City, UT 84112 USA. NCI, LTIB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 179 BP 47 EP 47 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600151 ER PT J AU Chua, MS Sausville, EA Hutchinson, I Bradshaw, TD Stevens, MFG AF Chua, MS Sausville, EA Hutchinson, I Bradshaw, TD Stevens, MFG TI Preclinical studies on 2-(4-amino-3-methylphenyl)benzothiazole SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Univ Nottingham, Canc Res Labs, Nottingham NG7 2RD, England. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 185 BP 49 EP 49 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600157 ER PT J AU Tomaszewski, JE Donohue, SJ Brown, AP Levine, BS Morrissey, RL Carter, CA Waud, WR Alley, MC AF Tomaszewski, JE Donohue, SJ Brown, AP Levine, BS Morrissey, RL Carter, CA Waud, WR Alley, MC TI Preclinical efficacy and toxicity of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU, NSC 364432) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 202 BP 53 EP 53 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600174 ER PT J AU Parchment, RE Tomaszewski, JE Grieshaber, CK Valeriote, FA Corbett, TH LoRusso, PM AF Parchment, RE Tomaszewski, JE Grieshaber, CK Valeriote, FA Corbett, TH LoRusso, PM TI In vitro hematotoxicology studies of neutropenia induced by the novel agent XK469 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. NCI, Preclin Toxicol & Pharmacol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 205 BP 54 EP 54 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600177 ER PT J AU Horti, J Dixon, SC Logothetis, CJ Guo, Y Reed, E Figg, WD AF Horti, J Dixon, SC Logothetis, CJ Guo, Y Reed, E Figg, WD TI Increased transcriptional activity of prostate specific antigen in the presence of TNP-470, an angiogenesis inhibitor SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 276 BP 73 EP 73 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600248 ER PT J AU Raptis, A Mavroudis, D Molldrem, J Tisdale, J Young, NS Phang, S Barrett, AJ AF Raptis, A Mavroudis, D Molldrem, J Tisdale, J Young, NS Phang, S Barrett, AJ TI Treatment of leukemic relapse following bone marrow transplantation SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, BMT Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 385O BP 80 EP 80 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100378 ER PT J AU Wigginton, JM Park, JW Jorcyk, CL Brunda, MJ Strieter, R Green, JE Wiltrout, RH AF Wigginton, JM Park, JW Jorcyk, CL Brunda, MJ Strieter, R Green, JE Wiltrout, RH TI Complete regression of autochthonous tumor and prevention of neoplastic progression by IL-12 pulse IL-2: Potential role of FAS/FAS-L SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, POB, DCS, Bethesda, MD 20892 USA. NCI, LC, DBS, Bethesda, MD 20892 USA. NCI, LEI, DBS, FCRDC, Frederick, MD 21701 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 313 BP 83 EP 83 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600285 ER PT J AU Khleif, SN Abrams, S Bastian, A Bergmann, E Chen, A Chung, Y Hamilton, JM Kohler, DR Morrison, G Schlom, J Allegra, C AF Khleif, SN Abrams, S Bastian, A Bergmann, E Chen, A Chung, Y Hamilton, JM Kohler, DR Morrison, G Schlom, J Allegra, C TI Vaccination of cancer patients carrying Ras mutations SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 325 BP 86 EP 86 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600297 ER PT J AU Gianni, W Bianco, V Pietropaolo, M Forti, G Todini, M Buoniconti, C Federici, GF Tonelli, C Audisio, RA Repetto, L Venturino, A Campisi, C Fratino, L Zagonel, V Marchei, P Marigliano, V AF Gianni, W Bianco, V Pietropaolo, M Forti, G Todini, M Buoniconti, C Federici, GF Tonelli, C Audisio, RA Repetto, L Venturino, A Campisi, C Fratino, L Zagonel, V Marchei, P Marigliano, V TI The first Italian academic experience on educational in geriatric oncology: specialistic course by University 'la Sapienza', Rome, Italy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Univ La Sapienza, GIOGer Geriatr Unit, Rome, Italy. Univ La Sapienza, Oncol Unit, Rome, Italy. European Inst Oncol, Milan, Italy. Natl Canc Inst, IST, Genoa, Italy. CNR, Rome, Italy. CRO, Aviano, Italy. RI zagonel, vittorina/F-4226-2014 OI zagonel, vittorina/0000-0002-0829-2525 NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 3 MA 163 BP 88 EP 88 PG 1 WC Oncology SC Oncology GA 135BG UT WOS:000076779500164 ER PT J AU Weinberger, C Niesor, E Bentzen, C AF Weinberger, C Niesor, E Bentzen, C TI The nuclear receptor FXR as a potential target for drugs regulating mevalonate-isoprenoid biosynthesis and cell growth SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NIEHS, Orphan Receptor Grp, Res Triangle Pk, NC 27709 USA. Symphar, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 414 BP 108 EP 108 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600386 ER PT J AU Senderowicz, AM Headlee, D Lush, R Arbuck, S Bauer, K Figg, WD Murgo, A Inoue, K Kobashi, S Kuwabara, T Sausville, EA AF Senderowicz, AM Headlee, D Lush, R Arbuck, S Bauer, K Figg, WD Murgo, A Inoue, K Kobashi, S Kuwabara, T Sausville, EA TI Phase I trial of infusional UCN-01, a novel protein kinase inhibitor, in patients with refractory neoplasms SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, DTP Clin Trials Unit, Med Branch, Bethesda, MD 20892 USA. NCI, CTEP, Bethesda, MD 20892 USA. Kyowa Hakko Kogyo Co Ltd, Tokyo 194, Japan. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 426 BP 111 EP 111 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600398 ER PT J AU Bjarnason, G Charpentier, D Winquist, E Wong, R Matthews, S Seymour, L AF Bjarnason, G Charpentier, D Winquist, E Wong, R Matthews, S Seymour, L TI Raltitrexed (Tomudex (TM)) plus doxorubicin (DOX) in patients with advanced gastric cancer: Interim results of a phase I dose escalation study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Canada Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 459 BP 120 EP 120 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600431 ER PT J AU Chan, KK Zhang, Z Chen, H Ganapathi, R Hayton, W Elson, P Hawk, E Kelloff, G Budd, GT AF Chan, KK Zhang, Z Chen, H Ganapathi, R Hayton, W Elson, P Hawk, E Kelloff, G Budd, GT TI Clinical pharmacokinetics of perillyl alcohol (POH) and metabolites following oral dosing SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Cleveland Clin, Cleveland, OH 44195 USA. Ohio State Univ, Columbus, OH 43210 USA. Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 476 BP 124 EP 124 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600448 ER PT J AU Burger, AM Fiebig, HH Newman, DJ Camalier, RF Sausville, EA AF Burger, AM Fiebig, HH Newman, DJ Camalier, RF Sausville, EA TI Antitumor activity of 17-allylaminogeldanamycin (NSC 330507) in melanoma xenografts is associated with decline in Hsp90 protein expression SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany. NCI, DTP, DCTD, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 504 BP 132 EP 132 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600476 ER PT J AU Michejda, CJ Cholody, WM Tarasov, S Hernandez, L Bansal, M Turpin, JA Rice, WG Aszalos, A AF Michejda, CJ Cholody, WM Tarasov, S Hernandez, L Bansal, M Turpin, JA Rice, WG Aszalos, A TI Bisimidazoacridones, potent but selective anti-tumor agents which appear to target transcription in sensitive cells SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 MADD, ABL, BRP, Frederick, MD USA. SAIC Frederick, LADM, DTP, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. US FDA, CBL, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 510 BP 133 EP 133 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600482 ER PT J AU Takebayashi, Y Goldwasser, F Pommier, Y AF Takebayashi, Y Goldwasser, F Pommier, Y TI Protein-linked DNA breaks induced by Ecteinascidin 743 in human colon carcinoma cells SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 531 BP 138 EP 138 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600503 ER PT J AU Bauer, KS Figg, WD Hamilton, JM Bergan, R Chen, A Dyer, V Walther, MM Linehan, WM Reed, E AF Bauer, KS Figg, WD Hamilton, JM Bergan, R Chen, A Dyer, V Walther, MM Linehan, WM Reed, E TI Phase II study of carboxyamido-triazole (CAI) in androgen independent prostate cancer (AIPC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 668 BP 174 EP 174 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600640 ER PT J AU Mani, S Michelassi, F Wade, J Kugler, J Gerstner, J Geoffroy, F Ansari, R Arrieta, R Murgo, A Schilsky, R Vokes, E AF Mani, S Michelassi, F Wade, J Kugler, J Gerstner, J Geoffroy, F Ansari, R Arrieta, R Murgo, A Schilsky, R Vokes, E TI Phase II trial of pyrazoloacridine (NSC 3661400) in patients with advanced pancreatic and hepatobiliary cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Phase 2 Consortium, Chicago, IL USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 673 BP 176 EP 176 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600645 ER PT J AU Al-Mohsen, I Hughes, WT AF Al-Mohsen, I Hughes, WT TI Systemic antifungal therapy: Past, present and future SO ANNALS OF SAUDI MEDICINE LA English DT Review ID INTRAVENOUS AMPHOTERICIN-B; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; NEUTROPENIC PATIENTS; CANDIDA-ALBICANS; ACUTE-LEUKEMIA; FLUCONAZOLE; PHARMACOKINETICS; DRUGS; PROPHYLAXIS C1 NCI, Pediat Canc Branch, Bethesda, MD 20892 USA. RP Hughes, WT (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA. NR 98 TC 17 Z9 18 U1 0 U2 1 PU K FAISAL SPEC HOSP RES CENTRE PI RIYADH PA PUBLICATIONS OFFICE PO BOX 3354, RIYADH 11211, SAUDI ARABIA SN 0256-4947 J9 ANN SAUDI MED JI Ann. Saudi Med. PD JAN PY 1998 VL 18 IS 1 BP 28 EP 38 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA ZU286 UT WOS:000074181500008 PM 17341911 ER PT J AU Lukish, JR Muro, K DeNobile, J Katz, R Williams, J Cruess, DF Drucker, W Kirsch, I Hamilton, SR AF Lukish, JR Muro, K DeNobile, J Katz, R Williams, J Cruess, DF Drucker, W Kirsch, I Hamilton, SR TI Prognostic significance of DNA replication errors in young patients with colorectal cancer SO ANNALS OF SURGERY LA English DT Article ID MICROSATELLITE INSTABILITY; MISMATCH REPAIR; MUTATOR PHENOTYPE; COLON-CANCER; CARCINOMA; CELLS; SEQUENCES; TOLERANT; HISTORY AB Objective To determine:he DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. Summary Background Data. Recent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. Methods All patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for when? the original archived pathology specimen could be retrieved sewed as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared is RER status. Results RER-positive tumors were found in 17 cases (47%). There was no significant difference in Dukes' stage or histologic grade at the time of diagnosis between patients with PER-positive tumors compared to RER-negative tumors. Patients with PER-positive tumors were found to have an improved prognosis: the 5-year survival probability for patients with RER-positive tumors was 68%, as compared to 32% for patients with RER-negative tumors (p < 0.05). Conclusions RER-positive tumors are common in young patients with CRC, and patients with RER-positive tumors have a significantly improved prognosis. Because of their young age, survival data and prognosis play an important role in the overall treatment plan of young patients with CRC. Therefore, knowledge of RER status could affect initial therapy, postoperative chemotherapy, and follow-up. C1 Natl Naval Med Ctr, Dept Surg, Bethesda, MD 20814 USA. Natl Naval Med Ctr, Dept Pathol, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21218 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Biostat, Bethesda, MD 20814 USA. NCI, USN, Med Oncol Branch, Bethesda, MD 20892 USA. RP Lukish, JR (reprint author), Natl Naval Med Ctr, Dept Surg, 8901 Wisconsin Ave, Bethesda, MD 20814 USA. FU NCI NIH HHS [CA47527, CA62924] NR 25 TC 95 Z9 98 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1998 VL 227 IS 1 BP 51 EP 56 DI 10.1097/00000658-199801000-00008 PG 6 WC Surgery SC Surgery GA YR054 UT WOS:000071453200008 PM 9445110 ER PT J AU Kim, CJ Cormier, J Roden, M Gritz, L Mazzara, GP Fetsch, P Hijazi, Y Lee, KH Rosenberg, SA Marincola, FM AF Kim, CJ Cormier, J Roden, M Gritz, L Mazzara, GP Fetsch, P Hijazi, Y Lee, KH Rosenberg, SA Marincola, FM TI Use of recombinant poxviruses to stimulate anti-melanoma T cell reactivity SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 17-23, 1997 CL CHICAGO, ILLINOIS SP Soc Surg Oncol DE melanoma; dendritic cells; melanoma-associated antigens; MART-1; recombinant viral vectors; poxviruses; CTL ID TUMOR-INFILTRATING LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; PERIPHERAL LYMPHOID ORGANS; DENDRITIC LANGERHANS CELLS; IN-VITRO; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; SOLUBLE-ANTIGEN; HLA-A2 SUBTYPES; OVARIAN-CANCER AB Background: Dendritic cells (DC) an potent professional antigen-presenting cells that can activate naive T lymphocytes and initiate cellular immune responses, As adjuvants, BC may be useful for enhancing immunogenicity and mediating tumor regression. Endogenous expression of antigen by DC could offer the potential advantage of allowing prolonged constitutive presentation of endogenously processed epitopes and exploitation of multiple restriction elements for the presentation of the same antigen. Methods: DC were prepared from the peripheral blood of HLA A*0201 patients with metastatic melanoma in the presence of IL-4 (1000 IU/mL) and GMCSF (1000 IU/mL). Recombinant vaccinia and fowlpox viruses encoding the hMART-1 gene were constructed and used to infect DC, The efficiency of infection and expression of the MART-1 antigen were assessed by immunohistochemistry and intracellular FAGS analyses. Cytotoxic lymphocytes (CTL) were generated by the stimulation of CD8+ T cells, with DC expressing the recombinant gene. Reactivity of the CTL was determined at weeks 1 and 2 by the amount of IFN-gamma released. Results: DC were infected with recombinant poxviruses and demonstrated specific melanoma antigen expression by immunohistochemistry, immunofluorescence, and intracellular FAGS analysis. The expression by DC of MART-1 MAA after viral infection was sufficient to generate CD8+ T lymphocytes that recognized naturally processed epitopes on tumor cells in 10 of 11 patients. Conclusions: Human DC are receptive to infection by recombinant poxviruses encoding MAA genes and are capable of efficiently processing and presenting these MAA to cytotoxic T cells. The potential advantage of this approach is the ability to present specific antigen independent of the identification of the epitope or the MHC restriction element, This strategy may be useful for the identification of relevant epitopes for a diverse number of HLA alleles and for active immunization in patients. C1 NCI, Dept Surg, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Pathol Lab, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. Ther Biol Corp, Cambridge, England. RP Marincola, FM (reprint author), NCI, Dept Surg, Surg Branch, Div Clin Sci, Bldg 10,Room 2B56, Bethesda, MD 20892 USA. NR 75 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN-FEB PY 1998 VL 5 IS 1 BP 64 EP 76 DI 10.1007/BF02303766 PG 13 WC Oncology; Surgery SC Oncology; Surgery GA YY525 UT WOS:000072156300013 PM 9524710 ER PT J AU Cabib, E Drgonova, J Drgon, T AF Cabib, E Drgonova, J Drgon, T TI Role of small G proteins in yeast cell polarization and wall biosynthesis SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE budding; Bud1/Rsr1; Cdc42; Rho1; beta(1 -> 3)glucan synthase ID GTP-BINDING PROTEIN; BUD-SITE-SELECTION; CORTICAL ACTIN CYTOSKELETON; RHO-TYPE GTPASES; SACCHAROMYCES-CEREVISIAE GENE; GUANINE-NUCLEOTIDE EXCHANGE; PHEROMONE-RESPONSE PATHWAY; RAS SUPERFAMILY GENES; MAP KINASE PATHWAY; BUDDING YEAST AB In the vegetative (mitotic) cycle and during sexual conjugation, yeast cells display polarized growth, giving rise to a bud or to a mating projection, respectively. In both cases one can distinguish three steps in these processes: choice of a growth site, organization of the growth site, and actual growth and morphogenesis. In all three steps, small GTP-binding proteins (G proteins) and their regulators play essential signaling functions. For the choice of a bud site, Bud1, a small G protein, Bud2, a negative regulator of Bud1, and Bud5, an activator, are all required. If any of them is defective, the cell loses its ability to select a proper bud position and buds randomly. In the organization of the bud site or of the site in which a mating projection appears, Cdc42, its activator Cdc24, and its negative regulators play a fundamental role. In the absence of Cdc42 or Cdc24, the actin cytoskeleton does not become organized and budding does not take place. Finally, another small G protein, Rho1, is required for activity of beta(1-->3)glucan synthase, the enzyme that catalyzes the synthesis of the major structural component of the yeast cell wall. In all of the above processes, G proteins can work as molecular switches because of their ability to shift between an active GTP-bound state and an inactive GDP-bound state. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Cabib, E (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM enricoc@bdg10.niddk.nih.gov; janad@bdg10.niddk.nih.gov; tomasd@bdg10.niddk.nih.gov RI Drgonova, Jana/B-2903-2008; OI Drgonova, Jana/0000-0002-4623-8466 NR 162 TC 142 Z9 145 U1 1 U2 9 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1998 VL 67 BP 307 EP 333 DI 10.1146/annurev.biochem.67.1.307 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 116JT UT WOS:000075721700013 PM 9759491 ER PT J AU Bewley, CA Gronenborn, AM Clore, GM AF Bewley, CA Gronenborn, AM Clore, GM TI Minor groove-binding architectural proteins: Structure, function, and DNA recognition SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE TATA box binding protein; HMG-box proteins; integration host factor; HMG I(Y); DNA bending ID RESOLUTION REFINED STRUCTURE; YEAST TFIIA/TBP/DNA COMPLEX; CRYSTAL-STRUCTURE; TATA-BOX; NUCLEOPROTEIN COMPLEXES; TRANSCRIPTION FACTORS; GENE-EXPRESSION; TBP; DOMAIN; SRY AB To date, high-resolution structures have been solved for five different architectural proteins complexed to their DNA target sites. These include TATA-box-binding protein, integration host factor (IHF), high mobility group I(Y)[HMG I(Y)], and the HMG-box-containing proteins SRY and LEF-1. Each of these proteins interacts with DNA exclusively through minor groove contacts and alters DNA conformation. This paper reviews the structural features of these complexes and the roles they play in facilitating assembly of higher-order protein-DNA complexes and discusses elements that contribute to sequence-specific recognition and conformational changes. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM clore@vger.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 63 TC 174 Z9 177 U1 0 U2 11 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1998 VL 27 BP 105 EP 131 DI 10.1146/annurev.biophys.27.1.105 PG 27 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZV620 UT WOS:000074324000006 PM 9646864 ER PT J AU Wlodawer, A Vondrasek, J AF Wlodawer, A Vondrasek, J TI Inhibitors of HIV-1 protease: A major success of structure-assisted drug design SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE AIDS; protease; drug design; inhibitors ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-DYNAMICS SIMULATION; FREE-ENERGY PERTURBATION; BINDING FREE-ENERGIES; CRYSTAL-STRUCTURE; TYPE-1 PROTEASE; ASPARTIC PROTEINASES; CATALYTIC DOMAIN; ACTIVE-SITE; 3-DIMENSIONAL STRUCTURE AB Retroviral protease (PR) from the human immunodeficiency virus type 1 (HTV-1) was identified over a decade ago as a potential target for structure-based drug design. This effort was very successful. Four drugs are already approved, and others are undergoing clinical trials. The techniques utilized in this remarkable example of structure-assisted drug design included crystallography, NMR, computational studies, and advanced chemical synthesis. The development of these drugs is discussed in detail. Other approaches to designing HIV-1 PR inhibitors, based on the concepts of symmetry and on the replacement of a water molecule that had been found tetrahedrally coordinated between the enzyme and the inhibitors, are also discussed. The emergence of drug-induced mutations of HIV-1 PR leads to rapid loss of potency of the existing drugs and to the need to continue the development process. The structural basis of drug resistance and the ways of overcoming this phenomenon are mentioned. C1 NCI, Macromol Struct Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Acad Sci Czech Republ, Inst Organ Chem & Biochem, CR-16610 Prague 6, Czech Republic. RP Wlodawer, A (reprint author), NCI, Macromol Struct Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI Vondrasek, JIri/A-4244-2008 NR 137 TC 461 Z9 471 U1 23 U2 166 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1998 VL 27 BP 249 EP 284 DI 10.1146/annurev.biophys.27.1.249 PG 36 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZV620 UT WOS:000074324000011 PM 9646869 ER PT J AU Bonifacino, JS Weissman, AM AF Bonifacino, JS Weissman, AM TI Ubiquitin and the control of protein fate in the secretory and endocytic pathways SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE proteasomes; ER degradation; quality control; endocytosis; lysosomes; adaptors ID CELL ANTIGEN RECEPTOR; FACTOR BETA-RECEPTOR; KAPPA-B-ALPHA; LIGAND-INDUCED POLYUBIQUITINATION; ENDOPLASMIC-RETICULUM MEMBRANE; GROWTH-HORMONE RECEPTOR; ACTIVATING ENZYME E1; CLASS-I MOLECULES; PROTEASOME PATHWAY; PLASMA-MEMBRANE AB The modification of proteins by chains of ubiquitin has long been known to mediate targeting of cytosolic and nuclear proteins for degradation by proteasomes. In this article, we discuss recent developments that reveal the involvement of ubiquitin in the degradation of proteins retained within the endoplasmic reticulum (ER) and in the internalization of plasma membrane proteins. Both luminal and transmembrane proteins retained in the ER are now known to be retrotranslocated into the cytosol in a process that involves ER chaperones and components of the protein import machinery. Once exposed to the cytosolic milieu, retro-translocated proteins are degraded by the proteasome, in most cases following polyubiquitination. There is growing evidence that both the ubiquitin-conjugating machinery and proteasomes may be associated with the cytosolic face of the ER membrane and that they could be functionally coupled to the process of retrotranslocation, The ubiquitination of plasma membrane proteins, on the other hand, mediates internalization of the proteins, which in most cases is followed by lysosomal/vacuolar degradation. There is, however, a well-documented case of a plasma membrane protein (the c-Met receptor) for which ubiquitination results in proteasomal degradation. These recent findings imply that ubiquitin plays more diverse roles in the regulation of the fate of cellular proteins than originally anticipated. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM juan@helix.nih.gov; amw@nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 163 TC 479 Z9 492 U1 2 U2 15 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 1998 VL 14 BP 19 EP 57 DI 10.1146/annurev.cellbio.14.1.19 PG 39 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 147CX UT WOS:000077471400003 PM 9891777 ER PT J AU Metzger, H AF Metzger, H TI Eureka! And other pleasures SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE philosophy of science; protein chemistry; scientific method ID BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E; PHASE-SEPARATION; DILUTE ANTISERUM; TRITON X-114; MAST-CELLS; IGE; RECEPTOR; DEGRANULATION AB At first one is very pleased at being invited to write a Prefatory Chapter, but as the delivery deadline draws closer one begins to think, "Oh my God! What on earth can I say that all but family members and few close friends will not find a great bore?" One solution is to write a scientific essay, but I concluded that that was a cop-out. I decided that perhaps the best tack to follow was to try to convey to the reader the personal characteristics I bring to my science and to other aspects of my professional career. The writing of this chapter has certainly convinced me that my particular background influenced what problems I chose to work on and how I approached their solution, but I hope that my results have a more ecumenical significance. There's been much written recently about how one's cultural background affects one's science, but I think that thesis can also be exaggerated. Science is a method of inquiry that by using certain guidelines permits rational individuals to observe Nature in a way that their findings will agree and have permanence. We shouldn't be diffident about defending that claim of objectivity. C1 NIAMSD, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMSD, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. EM hni@box-h.nih.gov NR 50 TC 4 Z9 4 U1 1 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1998 VL 16 BP 1 EP 25 DI 10.1146/annurev.immunol.16.1.1 PG 25 WC Immunology SC Immunology GA ZH616 UT WOS:000073129400001 PM 9597122 ER PT J AU Good, MF Kaslow, DC Miller, LH AF Good, MF Kaslow, DC Miller, LH TI Pathways and strategies for developing a malaria blood-stage vaccine SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE immune mechanisms; MSP-1; pathogenesis ID MEROZOITE SURFACE PROTEIN-1; PLASMODIUM-FALCIPARUM MALARIA; TUMOR-NECROSIS-FACTOR; NON-EXPOSED DONORS; T-CELL EPITOPES; CIRCUMSPOROZOITE PROTEIN; CEREBRAL MALARIA; TERMINAL FRAGMENT; INTERFERON-GAMMA; AOTUS MONKEYS AB In the past 10 years, our knowledge of the malaria parasite has increased enormously: identification and analysis of parasite antigens, demonstration of protection of monkeys and mice following immunization with these antigens, and better understanding of the mechanisms of immunity to malaria and the pathogenesis of disease in malaria. Powerful new adjuvants have been developed, some of which-it is hoped-will be suitable for human use. Recently, a successful human trial of a vaccine aimed at sporozoites (the stage inoculated by mosquitoes) was completed. However, it is the red blood cell stage of the parasite that causes disease, and it is against this stage-in which the parasite grows at an exponential rate-that it has proven very difficult to induce a protective immune response by vaccination. This review focuses on recent exciting developments toward a blood-stage vaccine. We analyze the major obstacles to vaccine development and outline a strategy involving public-and industry-funded research that should result in development of a vaccine. C1 Queensland Inst Med Res, Cooperat Res Ctr Vaccine Technol, Brisbane, Qld 4029, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Good, MF (reprint author), Queensland Inst Med Res, Cooperat Res Ctr Vaccine Technol, Brisbane, Qld 4029, Australia. NR 95 TC 119 Z9 128 U1 0 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1998 VL 16 BP 57 EP 87 DI 10.1146/annurev.immunol.16.1.57 PG 31 WC Immunology SC Immunology GA ZH616 UT WOS:000073129400003 PM 9597124 ER PT J AU Letterio, JJ Roberts, AB AF Letterio, JJ Roberts, AB TI Regulation of immune responses by TGF-beta SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE T cells; B cells; macrophage; dendritic cell; autoimmune disease ID TRANSFORMING-GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; MYELIN BASIC-PROTEIN; T-CELL GROWTH; HUMAN LYMPHOCYTES-T; HUMAN B-LYMPHOCYTES; HUMAN-MONOCYTES; IN-VITRO; PERITONEAL-MACROPHAGES; NEUTROPHIL FUNCTION AB The transforming growth factor beta (TGF-beta) family of proteins are a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties. TGF-beta 1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these immune cells. TGF-beta can modulate expression of adhesion molecules, provide a chemotactic gradient for leukocytes and other cells participating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-beta have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to the fibrotic complications associated with chronic inflammatory conditions. In addition to these roles in disease pathogenesis, TGF-beta is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cells that are induced in this process. The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-beta gene knockout and transgenic mice, supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function. C1 NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. RP Letterio, JJ (reprint author), NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. EM Robertsa@dce41.nci.nih.gov NR 132 TC 1339 Z9 1388 U1 8 U2 64 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1998 VL 16 BP 137 EP 161 DI 10.1146/annurev.immunol.16.1.137 PG 25 WC Immunology SC Immunology GA ZH616 UT WOS:000073129400006 PM 9597127 ER PT J AU Leonard, WJ O'Shea, JJ AF Leonard, WJ O'Shea, JJ TI JAKS AND STATS: Biological implications SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE cytokines; interferons; signaling; transcriptional activation; tyrosine phosphorylation ID PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; SIGNAL-TRANSDUCTION PATHWAY; COLONY-STIMULATING FACTOR; GROWTH-HORMONE RECEPTOR; DEFECTIVE LYMPHOID DEVELOPMENT; DNA-BINDING ACTIVITY; INTERFERON-GAMMA; MOLECULAR-CLONING; IL-2 RECEPTOR AB Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hematopoietic system. These factors stimulate proliferation, differentiation, and survival signals, as well as specialized functions in host resistance to pathogens. Although cytokines are known to activate multiple signaling pathways that together mediate these important functions, one of these pathways, the Jak-STAT pathway, is the focus of this chapter. This pathway is triggered by both cytokines and interferons, and it very rapidly allows the transduction of an extracellular signal into the nucleus. The pathway uses a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT protein dimerization and nuclear translocation. STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov; osheaj@arb.niams.nih.gov NR 184 TC 1139 Z9 1166 U1 8 U2 62 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1998 VL 16 BP 293 EP 322 DI 10.1146/annurev.immunol.16.1.293 PG 30 WC Immunology SC Immunology GA ZH616 UT WOS:000073129400011 PM 9597132 ER PT J AU Holland, SM Gallin, JI AF Holland, SM Gallin, JI TI Evaluation of the patient with recurrent bacterial infections SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE neutrophils; monocytes; chronic granulomatous disease; interferon-gamma ID CHRONIC GRANULOMATOUS-DISEASE; HYPERIMMUNOGLOBULIN-E; INTERFERON-GAMMA; CHRONIC NEUTROPENIA; CLINICAL-FEATURES; JOBS SYNDROME; DEFICIENCY; IMMUNODEFICIENCY; MANIFESTATIONS; DYSFUNCTION AB Recurrent bacterial infection is a complaint encountered regularly in the course of both adult and pediatric care. Defects of neutrophils and monocytes are most commonly associated with recurrent infection, but abnormalities of immunoglobulins and complement must be considered. Defensins, small antibacterial peptides, have been implicated recently in some of the infectious diathesis of cystic fibrosis. A thorough history and physical examination focused on severity, sequelae, and microbiology of infections can usually determine whether a patient needs further evaluation. The diseases and syndromes most frequently associated with recurrent infection are presented, along with discriminating clinical, pathologic, and microbiologic features. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smh@nih.gov NR 57 TC 17 Z9 18 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1998 VL 49 BP 185 EP 199 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA ZG853 UT WOS:000073046600013 PM 9509258 ER PT J AU Felder, CC Glass, M AF Felder, CC Glass, M TI Cannabinoid receptors and their endogenous agonists SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE marijuana; anandamide; fatty acid ethanolamide; cannabinoids; receptors ID MEDIATED SIGNAL-TRANSDUCTION; CEREBRAL-CORTEX SLICES; RAT-BRAIN MEMBRANES; ADENYLATE-CYCLASE; ARACHIDONIC-ACID; ANANDAMIDE ANALOGS; N-ARACHIDONOYLETHANOLAMINE; MOLECULAR CHARACTERIZATION; PHARMACOLOGICAL ACTIVITY; NEUROBLASTOMA-CELLS AB Marijuana has been in use for over 4000 years as a therapeutic and as a recreational drug. Within the past decade, two cannabinoid receptor types have been identified, their signal transduction characterized, and an endogenous lipid agonist isolated from mammalian tissues. The CB1 cannabinoid receptor is widely distributed in mammalian tissues, with the highest concentrations found in brain neurons. CB1 receptors are coupled to modulation of adenylate cyclase and ion channels. The CB2 receptor is found in cells of the immune system and is coupled to inhibition of adenylate cyclase. Both receptor types selectively bind Delta(9)-THC, the active principle in marijuana, and anandamide (arachidonylethanolamide), an endogenous cannabimimetic eicosanoid. Progress is being made in the development of novel agonists and antagonists with receptor subtype selectivity, mice with genetic deletion of the cannabinoid receptors, and receptor-specific antibodies, which should help in providing a better understanding of the physiological role of the cannabinoid receptors. C1 Eli Lilly & Co, Lilly Res Labs, Neurosci Discovery, Indianapolis, IN 46285 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Felder, CC (reprint author), Eli Lilly & Co, Lilly Res Labs, Neurosci Discovery, Indianapolis, IN 46285 USA. EM felder@lilly.com OI Glass, Michelle/0000-0002-5997-6898 NR 133 TC 265 Z9 269 U1 1 U2 14 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1998 VL 38 BP 179 EP 200 DI 10.1146/annurev.pharmtox.38.1.179 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZL883 UT WOS:000073483100008 PM 9597153 ER PT J AU Spring, KR AF Spring, KR TI Routes and mechanism of fluid transport by epithelia SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE water permeability; tight junction; standing-osmotic gradient; solvent drag; lateral intercellular space ID LATERAL INTERCELLULAR SPACES; NECTURUS GALLBLADDER EPITHELIUM; PSEUDO-STREAMING POTENTIALS; CHOROID-PLEXUS EPITHELIUM; OSMOTIC WATER-FLOW; PROXIMAL TUBULE; TIGHT-JUNCTION; FLUORESCENCE MICROSCOPY; MEMBRANE-PROTEINS; COLONIC CRYPTS AB The mechanism of fluid transport by leaky epithelia and the route taken by the transported fluid are in dispute. A consideration of current mathematical models for coupling of solutes and water, as well as the methodologies for the study of fluid transport, shows that local osmosis best accounts for water movement. Although it seems virtually certain that the tight junctions are water permeable, the fraction of absorbed fluid that crosses the tight junction cannot yet be determined with confidence. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. EM Springk@fido.nhlbi.nih.gov NR 78 TC 137 Z9 138 U1 0 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1998 VL 60 BP 105 EP 119 DI 10.1146/annurev.physiol.60.1.105 PG 15 WC Physiology SC Physiology GA ZD697 UT WOS:000072713900006 PM 9558456 ER PT J AU Dufau, ML AF Dufau, ML TI The luteinizing hormone receptor SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE hormone binding; signal transduction; gene structure; gene regulation; disease states ID CHORIONIC-GONADOTROPIN RECEPTOR; LUTROPIN-CHORIOGONADOTROPIN RECEPTOR; LEUCINE-RICH REPEATS; LIMITED PRECOCIOUS PUBERTY; HUMAN THYROTROPIN RECEPTOR; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; BETA-ADRENERGIC RECEPTORS; 2ND TRANSMEMBRANE DOMAIN; RAT LEYDIG-CELLS AB The luteinizing hormone receptor (LHR) is a member of the subfamily of glycoprotein hormone receptors within the superfamily of G protein-coupled receptor (GPCR)/seven-transmembrane domain receptors. Over the past eight years, major advances have been made in determining the structure and function of the LHR and its gene. The hormone-binding domain has been localized to exons 1-7 in the extracellular (EC) domain/region of the receptor, which contains several leucine-rich repeats. High-affinity binding of LH and human chorionic gonadotropin (hCG) causes secondary hormone or receptor contacts to be established with regions of the EC loop/transmembrane module that initiate signal transduction. Models of hormone-receptor interaction have been derived from the crystal structures of hCG and of the ribonuclease inhibitor, which also contains leucine-rich repeats. Such models provide a framework for the interpretation of mutational studies and for further experiments. The extracellular domain of the receptor has been overexpressed in vitro, which will facilitate crystallographic resolution of the structure of the receptor-binding site. The transmembrane domain/loop/cytoplasmic module transduces the signal for coupling to G proteins. Several constitutive, activating mutations that cause human disease have been found in helix VI and adjacent structures. These mutations have provided valuable information about mechanisms of signal transfer and G protein coupling. The structure of the LHR gene has been elucidated, and the regulation of its transcription is beginning to be understood. Valuable insights into receptor evolution have been derived from analysis of sequence homologies, the gene structure of glycoprotein hormone receptors and other members of the GPCR family, and the glycoprotein hormone receptor-like precursors identified in several invertebrate species. C1 NICHHD, Mol Endocrinol Sect, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Mol Endocrinol Sect, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM dufau@helix.nih.gov NR 167 TC 237 Z9 244 U1 0 U2 13 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1998 VL 60 BP 461 EP 496 DI 10.1146/annurev.physiol.60.1.461 PG 36 WC Physiology SC Physiology GA ZD697 UT WOS:000072713900023 PM 9558473 ER PT J AU King, KL Cidlowski, JA AF King, KL Cidlowski, JA TI Cell cycle regulation and apoptosis SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE p53; pRb; E2F; cell death; cell cycle; lymphocytes ID RETINOBLASTOMA GENE-PRODUCT; TUMOR-SUPPRESSOR GENE; S-PHASE ENTRY; WILD-TYPE P53; C-MYC; GLUCOCORTICOID REGULATION; LYMPHOMA-CELLS; IN-VIVO; P53-MEDIATED APOPTOSIS; MEDIATED APOPTOSIS AB Tissue homeostasis requires a balance between cell proliferation and death. Apoptosis and proliferation are linked by cell cycle regulators, and apoptotic stimuli affect both cell proliferation and death. Glucocorticoids induce G1 arrest and apoptosis in transformed lymphoid cells. Decreased expression of the cell cycle components c-myc and cyclin D3 is essential for glucocorticoid-induced growth arrest and death in dividing cells. Other G1 regulators, such as p53, pRb, and E2F, have also been implicated in apoptosis. Mice lacking either p53 or E2F display aberrant cell proliferation and tumor formation, suggesting that these proteins are involved in the elimination of abnormal cells through apoptosis. In contrast, pRb induces G1 arrest and suppresses apoptosis in cultured cells. Mice that lack pRb are nonviable and show ectopic mitosis and massive cell death, suggesting that pRb is an apoptotic suppressor. Further analysis of common components of apoptotic and cell cycle machinery may provide insight into the coordinated regulation of these antagonistic processes. C1 Univ Cincinnati, Med Ctr, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP King, KL (reprint author), Univ Cincinnati, Med Ctr, Dept Cellular & Mol Physiol, POB 670576, Cincinnati, OH 45267 USA. EM cidlowski@niehs.nih.gov NR 95 TC 306 Z9 338 U1 3 U2 11 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1998 VL 60 BP 601 EP 617 DI 10.1146/annurev.physiol.60.1.601 PG 17 WC Physiology SC Physiology GA ZD697 UT WOS:000072713900028 PM 9558478 ER PT J AU Pettit, GR Flahive, EJ Boyd, MR Bai, RL Hamel, E Pettit, RK Schmidt, JM AF Pettit, GR Flahive, EJ Boyd, MR Bai, RL Hamel, E Pettit, RK Schmidt, JM TI Antineoplastic agents 360. Synthesis and cancer cell growth inhibitory studies of dolastatin 15 structural modifications SO ANTI-CANCER DRUG DESIGN LA English DT Article DE antineoplastic agents; depsipeptide; dolastatin 15; structural modifications; tubulin inhibition ID MARINE NATURAL-PRODUCTS; DOLABELLA-AURICULARIA; ANTIMITOTIC AGENTS; AMINO-ACIDS; TUBULIN; PEPTIDE; BINDING; SCREEN; LINES; MICROTUBULES AB Dolastatin 15 (1), a potent antineoplastic constituent of the Indian Ocean shell-less mollusk Dolabella auricularia, was utilized as the lead substance for a series of structure-activity studies. The synthetic methods, in vitro evaluations against a variety of murine and human cancer cell lines, as well as a selection of bacteria and fungi, and inhibition of tubulin polymerization are described. Remarkably, all of the compounds studied, in which the C-terminal (S)-dolapyrrolidinone unit (Dpy) was replaced with a series of structurally diverse and more readily available amides, showed cancer cell growth inhibition activities generally quite comparable to those of the parent molecule (1). All analogues, however, were less potent than 1 as inhibitors of tubulin polymerization. The structurally modified peptides, like the parent compound, caused mitotic arrest in cultured cells, consistent with tubulin being the primary cellular target. The ability of dolastatin 15 and eight modifications or precursors thereof to inhibit the growth of a Gram-negative bacterium suggests that these compounds have an additional target distinct from tubulin. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. NCI, Lab Drug Discovery Res & Dev, DTP, DCTDC,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Box 872404, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA-44344-01-09] NR 39 TC 18 Z9 18 U1 0 U2 1 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 JAN PY 1998 VL 13 IS 1 BP 47 EP 66 PG 20 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA YW192 UT WOS:000071907700004 PM 9474242 ER PT J AU Steingold, SF Sharp, NJ McGahan, MC Hughes, CS Dunn, SE Page, RL AF Steingold, SF Sharp, NJ McGahan, MC Hughes, CS Dunn, SE Page, RL TI Characterization of canine MDR1 mRNA: Its abundance in drug resistant cell lines and in vivo SO ANTICANCER RESEARCH LA English DT Article DE MDR1; reverse transcriptase polymerase chain reaction; drug resistance; P-glycoprotein; canine ID POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMAS; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; MESSENGER-RNA; CANCER-CELLS; QUANTITATION AB Background: Overexpression of the MDR1 gene often contributes to antineoplastic drug resistance. The purpose of this study was to characterize the canine MDR1 mRNA homologue and evaluate its expression in both canine cell lines and lymphomas. Materials and Methods: The abundance of the canine MDR1 transcript was assessed in three resistant cell lines and in pretreatment canine lymphoma wing semi-quantitative RT/PCR. Results: Canine transcript was 4.5 Kb with 9.3% sequence homology to human MDR1, and 90% homology to mouse and hamster equivalent genes. Increase in MDR1 transcript levels was observed in three progressively resistant canine cell lines. De novo MDR1 transcript expression was independent of response to therapy in dogs with lymphoma. Conclusions: We conclude that the canine MDR1 mRNA homologue is structurally similar to the human transcript. Expression of MDR1 mRNA correlates with in vitro drug sensitivity but does not correlate with in vivo doxorubicin sensitivity in canine lymphoma. C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NIEHS, Raleigh, NC USA. RP Page, RL (reprint author), N Carolina State Univ, Coll Vet Med, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM rodney_page@ncsu.edu FU NCI NIH HHS [CA29582] NR 26 TC 21 Z9 21 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1998 VL 18 IS 1A BP 393 EP 400 PG 8 WC Oncology SC Oncology GA ZG009 UT WOS:000072955500068 PM 9568108 ER PT J AU Graybill, JR Najvar, LK Fothergill, A Hardin, T Rinaldi, M Lambros, C Regen, SL AF Graybill, JR Najvar, LK Fothergill, A Hardin, T Rinaldi, M Lambros, C Regen, SL TI KY-62, a polyene analog of amphotericin B, for treatment of murine candidiasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID METHYL-ESTER; LEUKOENCEPHALOPATHY; CELLS AB KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S TExas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Lehigh Univ, Bethlehem, PA 18015 USA. NIAID, Bethesda, MD 20892 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIAID NIH HHS [N01-AI-25141] NR 25 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1998 VL 42 IS 1 BP 147 EP 150 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YP659 UT WOS:000071301100023 PM 9449275 ER PT J AU Donovan, PJ De Miguel, M Cheng, LZ Resnick, JL AF Donovan, PJ De Miguel, M Cheng, LZ Resnick, JL TI Primordial germ cells, stem cells and testicular cancer SO APMIS LA English DT Article; Proceedings Paper CT 4th Copenhagen Workshop on Carcinoma In Situ and Cancer of the Testis - Molecular and Endocrine Aspects CY MAY 18-21, 1997 CL COPENHAGEN UNIV HOSP, COPENHAGEN, DENMARK HO COPENHAGEN UNIV HOSP DE germ cells; c-kit/Steel factor; Lif; bFGF; EG cells; teratocarcinoma ID LEUKEMIA INHIBITORY FACTOR; TYROSINE KINASE RECEPTOR; ONCOGENE C-KIT; GROWTH-FACTOR; PROTO-ONCOGENE; W-LOCUS; MOUSE; CULTURE; MUTATION; LIGAND AB Primordial Germ Cells (PGCs) arise in the mouse embryo as a small population of cells some way from the gonad anlagen. In order for the embryo to develop into a fully fertile adult animal the PGCs must increase in number and reach the gonad. Mutations causing sterility in the mouse have identified some of the genes involved in regulating PGC development and some of these genes have been molecularly cloned. Similarly mutations affecting the development and differentiation of PCC-derived tumors (teratomas and teratocarcinomas) have been identified in certain strains of mice and these identify genes involved in the normal growth and differentiation of PGCs. These studies should help to define the role of growth factors in PGC development and in the development of germ-cell-derived tumors. C1 Univ Alcala de Henares, Dept Genet & Cell Biol, Madrid, Spain. Gryphon Pharmaceut, Stem Cell Mol Biol, Baltimore, MD USA. Univ Florida, Dept Microbiol & Mol Genet, Gainesville, FL 32611 USA. RP Donovan, PJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Cell Biol Dev & Differentiat Grp, ABL Basic Res Program, POB B,Bldg 539, Frederick, MD 21702 USA. NR 46 TC 16 Z9 18 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD JAN PY 1998 VL 106 IS 1 BP 134 EP 141 PG 8 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA ZA193 UT WOS:000072338300029 PM 9524571 ER PT J AU McLachlan, JA Newbold, RR Li, SF Negishi, M AF McLachlan, JA Newbold, RR Li, SF Negishi, M TI Are estrogens carcinogenic during development of the testes? SO APMIS LA English DT Article; Proceedings Paper CT 4th Copenhagen Workshop on Carcinoma In Situ and Cancer of the Testis - Molecular and Endocrine Aspects CY MAY 18-21, 1997 CL COPENHAGEN UNIV HOSP, COPENHAGEN, DENMARK HO COPENHAGEN UNIV HOSP DE testicular neoplasms; estrogens; environmental disrupters ID REPRODUCTIVE-TRACT; NEOPLASTIC TRANSFORMATION; CELL-TRANSFORMATION; DIETHYLSTILBESTROL; MICE; EXPOSURE; GENE; ANEUPLOIDY; INDUCTION; INUTERO AB Many chemicals in the environment mimic the female sex hormone, estrogen. Exposure to environmental estrogens during early fetal development was proposed by Sharpe & Skakkebaek as a potential risk factor for subsequent testicular disease, including neoplasia and poor semen quality. To understand the mechanisms of action of estrogenic chemicals during differentiation of the male genital tract. we have studied developmental exposure to the synthetic estrogen, diethylstilboestrol (DES). While DES is a much more potent estrogen than most environmental chemicals examined, several of these compounds share some of the same properties as DES? such as a relative lack of binding to serum estrogen carrying proteins. Prenatal exposure to DES is associated with poor semen quality, prostatic disease, cryptorchidism and testicular neoplasia in mice. A rare form of testicular cancer, rete testis carcinoma, was observed in five percent of male mice treated in utero, with DES. We also demonstrated altered regulation of an estrogen responsive gene, lactotransferrin (LTF) in the seminal vesicles of treated mice, but not the controls. Likewise, LTF was irreversibly altered in the uteri of developmentally treated females; at the molecular level altered methylation of the gene appears to be involved, thus, providing a potential marker for hormonal effects during development. The induction of permanent or "imprinted" responses during the development of a relatively estrogen-free reproductive tract cell suggests that undifferentiated targets for estrogen action may be sites for subsequent growth and differentiation defects associated with neoplasia. C1 Tulane Univ, Tulane Xavier Ctr Bioenvironm Res, New Orleans, LA 70112 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP McLachlan, JA (reprint author), Tulane Univ, Tulane Xavier Ctr Bioenvironm Res, 1430 Tulane Ave, New Orleans, LA 70112 USA. NR 24 TC 28 Z9 29 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD JAN PY 1998 VL 106 IS 1 BP 240 EP 242 PG 3 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA ZA193 UT WOS:000072338300055 PM 9524585 ER PT J AU Hyman, SE AF Hyman, SE TI The K-05 award controversy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Rockville, MD 20857 USA. RP Hyman, SE (reprint author), NIMH, 5600 Fishers Ln, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1998 VL 55 IS 1 BP 21 EP 22 DI 10.1001/archpsyc.55.1.21 PG 2 WC Psychiatry SC Psychiatry GA YP667 UT WOS:000071301900005 PM 9435755 ER PT J AU Kumra, S Jacobsen, LK Rapoport, JL AF Kumra, S Jacobsen, LK Rapoport, JL TI Childhood-onset schizophrenia - In reply SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID CLOZAPINE C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 6N240,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1998 VL 55 IS 1 BP 91 EP 92 PG 2 WC Psychiatry SC Psychiatry GA YP667 UT WOS:000071301900022 ER PT J AU Heseltine, PNR Goodkin, K Atkinson, JH Vitiello, B Rochon, J Heaton, RK Eaton, EM Wilkie, FL Sobel, E Brown, SJ Feaster, D Schneider, L Goldschmidts, WL Stover, ES AF Heseltine, PNR Goodkin, K Atkinson, JH Vitiello, B Rochon, J Heaton, RK Eaton, EM Wilkie, FL Sobel, E Brown, SJ Feaster, D Schneider, L Goldschmidts, WL Stover, ES TI Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment SO ARCHIVES OF NEUROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE PROTEIN; RECEPTOR-BINDING; AIDS; OCTAPEPTIDES; INFECTIVITY; INDIVIDUALS; COMPLEX AB Background: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp 120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. Objective: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. Patients and Methods: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4(+) cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP store derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4(+) count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. Results: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4(+) cell count between treatment arms, analyses were also adjusted for this variable. These CD4(+)-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4(+) cell count was above 0.200 x 10(9)/L (200 cells/mu) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). Conclusions: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment tie, NP global deficit score greater than or equal to 0.5) or with relatively preserved immunological status tie, CD4(+) cell count > 0.200 x 10(9)/L). C1 Univ So Calif, Los Angeles Cty Med Ctr, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Epidemiol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Miami, Dept Psychiat, Miami, FL 33152 USA. NIMH, Off AIDS, Rockville, MD 20857 USA. George Washington Biostat Ctr, Rockville, MD USA. RP Heseltine, PNR (reprint author), Univ So Calif, Los Angeles Cty Med Ctr, Dept Med, 1200 N State St,Box 596, Los Angeles, CA 90033 USA. RI Feaster, Daniel/I-6079-2013 FU NIMH NIH HHS [N01MH00013, N01MH20004, N01MH20007] NR 57 TC 54 Z9 57 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 1998 VL 55 IS 1 BP 41 EP 51 DI 10.1001/archneur.55.1.41 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA YR191 UT WOS:000071469900005 PM 9443710 ER PT J AU Gerber, LH Binder, H Berry, R Siegel, KL Kim, H Weintrob, J Lee, YJ Mizell, S Marini, J AF Gerber, LH Binder, H Berry, R Siegel, KL Kim, H Weintrob, J Lee, YJ Mizell, S Marini, J TI Effects of withdrawal of bracing in matched pairs of children with osteogenesis imperfecta SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article AB Objectives: To evaluate the effects of withdrawal of long-leg braces (hip-knee-ankle-foot orthoses [HKAFO]) on activity and ambulation in children with osteogenesis imperfecta. Design: A prospective, randomized cross-over trial, that describes the effects of withdrawing HKAFO. Patients: Ten children who were ambulatory with the assistance of braces. All had type III or IV osteogenesis imperfecta. Children were paired for age and clinical severity. Strength testing, fractures, and independence in daily activity were monitored at 4-month intervals for 32 months (16 months each of braced and unbraced periods). Gait was analyzed during braced and unbraced conditions. Results: Muscle strength declined .35 grade during unbraced and .1 grade during braced intervals. Children spent more time in upright activity during braced intervals than during unbraced intervals (p = .17). Children were more independent in daily activities during braced than during unbraced periods (p = .14). Seventeen fractures of lower extremities occurred during all the unbraced periods, and 8 occurred during the braced intervals (p = .08): the fracture rate was higher during unbraced intervals. (p = .06) Bracing was associated with increased hip flexion and stride length and decreased transverse plane pelvic rotation. Conclusion: Withdrawal of HKAFO in children with osteogenesis imperfecta who had achieved upright activity was not associated with significant decrease in muscle strength or independence, but there was an associated increase in fracture rare that nearly reached significance. C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. Orthot Prosthet Ctr, Fairfax, VA USA. RP Gerber, LH (reprint author), NIH, Dept Rehabil Med, 10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 10 TC 13 Z9 14 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 1998 VL 79 IS 1 BP 46 EP 51 DI 10.1016/S0003-9993(98)90207-6 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA YQ458 UT WOS:000071389600012 PM 9440417 ER PT J AU Hoshino, Y Jones, RW Kapikian, AZ AF Hoshino, Y Jones, RW Kapikian, AZ TI Serotypic characterization of outer capsid spike protein VP4 of vervet monkey rotavirus SA11 strain SO ARCHIVES OF VIROLOGY LA English DT Article ID PLAQUE-REDUCTION NEUTRALIZATION; MONOCLONAL-ANTIBODIES; EQUINE ROTAVIRUSES; PORCINE ROTAVIRUS; IDENTIFICATION; GENE; SPECIFICITIES; INFECTIVITY; HEMAGGLUTINATION; ENHANCEMENT AB The vervet monkey rotavirus SA11, a prototype strain of group A rotaviruses, has been shown to possess VP7 serotype 3 specificity but its neutralization specificity with regard to the other outer capsid protein VP4 has not been elucidated. We thus determined its VP4 specificity by two-way cross-neutralization with guinea pig antiserum prepared with a single gene substitution reassortant that had only the VP4-encoding gene from the simian rotavirus SA11 strain and remaining ten genes from human rotavirus DS-1 strain (G serotype 2). The SA11 VP4 was related antigenically in a one-way fashion to rhesus monkey rotavirus MMU18006 VP4 (a P5B strain) and marginally to human and canine rotavirus VP4s with P serotype 5A specificity. In addition, the SA11 VP4 was shown to be distinct antigenically from those of other known P serotypes (1-4, and 6-11) as well as those of uncharacterized equine, lapine, and avian rotavirus strains. The SA11 VP4 is thus proposed for classification as a P5B serotype. C1 NIAID, ES, LID, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, ES, LID, NIH, Bldg 7,Room 105,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 59 TC 25 Z9 25 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1998 VL 143 IS 6 BP 1233 EP 1244 DI 10.1007/s007050050371 PG 12 WC Virology SC Virology GA ZU638 UT WOS:000074218100018 PM 9687880 ER PT J AU Meng, XJ Halbur, PG Haynes, JS Tsareva, TS Bruna, JD Royer, RL Purcell, RH Emerson, SU AF Meng, XJ Halbur, PG Haynes, JS Tsareva, TS Bruna, JD Royer, RL Purcell, RH Emerson, SU TI Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV SO ARCHIVES OF VIROLOGY LA English DT Article ID ACUTE VIRAL-HEPATITIS; TRANSMITTED NON-A; NON-B HEPATITIS; SYNTHETIC PEPTIDES; MOLECULAR-BIOLOGY; PROTOTYPE STRAIN; SEROPREVALENCE; ANTIBODIES; MONKEYS; FAILURE AB A novel virus of pigs, swine hepatitis E virus (swine HEV), was recently identified and shown to be antigenically and genetically related to human HEV. In the present study, we attempted to infect specific-pathogen-free (SPF) pigs experimentally with swine HEV or with human strains of HEV. Serum samples collected from naturally infected pigs were used as the source of swine HEV. Pigs inoculated intravenously with serum samples containing swine HEV seroconverted to anti-HEV 4 to 8 weeks postinoculation, and the virus spread to an uninoculated pig. Swine HEV was detected in nasal and rectal swab materials as early as 2 weeks postinoculation and for 4 to 8 weeks thereafter. Viremia appeared 4 to 6 weeks postinoculation and lasted 1 to 3 weeks. The inoculated pigs appeared clinically normal and serum liver enzymes were not significantly elevated. In contrast, pigs were not infected when inoculated int ravenously with about 10(5) monkey infectious doses of one of two human strains of HEV (Sar-55 or Mex-14). C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Coll Vet Med, Ames, IA 50011 USA. RP Meng, XJ (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 206,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 38 TC 152 Z9 165 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1998 VL 143 IS 7 BP 1405 EP 1415 DI 10.1007/s007050050384 PG 11 WC Virology SC Virology GA 108MD UT WOS:000075269400012 PM 9722883 ER PT J AU Gowda, S Satyanarayana, T Naidu, RA Mushegian, A Dawson, WO Reddy, DVR AF Gowda, S Satyanarayana, T Naidu, RA Mushegian, A Dawson, WO Reddy, DVR TI Characterization of the large (L) RNA of peanut bud necrosis tospovirus SO ARCHIVES OF VIROLOGY LA English DT Article ID SPOTTED WILT VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; DEFECTIVE INTERFERING RNA; S-RNA; FAMILY BUNYAVIRIDAE; GENOME ORGANIZATION; BUNYAMWERA VIRUS; SEGMENT; POLYMERASE; PROTEINS AB The nucleocapsids purified from peanut plants systemically infected with peanut bud necrosis virus (PBNV), a member of the genus Tospovirus, contained both viral(v) and viral complementary(vc) sense L RNAs. Defective forms of L RNA containing 'core polymerase region' were observed. The full length L RNA of PBNV was sequenced using overlapping cDNA clones. The 8911 nucleotide L RNA contains a single open reading frame (ORF) in the vc strand, and encodes a protein of 330 kDa. At the 5' and 3' termini of the v sense RNA there were 247 and 32 nt untranslated regions, respectively, containing an 18 nt complementary sequence with one mismatch. Comparisons of the predicted amino acid sequence of the L protein of PBNV with other members of Bunyaviridae suggest that the L protein of PBNV is a viral polymerase. The L protein had highest identity in the 'core-polymerase domain' with the corresponding regions of other tospoviruses, tomato spotted wilt virus and impatiens necrotic spot virus. C1 Univ Florida, Ctr Citrus Res & Educ, Lake Alfred, FL 33850 USA. Int Crops Res Inst Semi Arid Trop, Crop Protect Div, Patancheru, Andhra Pradesh, India. Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD USA. RP Gowda, S (reprint author), Univ Florida, Ctr Citrus Res & Educ, 700 Expt Stn Rd, Lake Alfred, FL 33850 USA. RI Rayapati, Naidu/A-7125-2009; OI Mushegian, Arcady/0000-0002-6809-9225 NR 33 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1998 VL 143 IS 12 BP 2381 EP 2390 DI 10.1007/s007050050468 PG 10 WC Virology SC Virology GA 166PR UT WOS:000078586500009 PM 9930194 ER PT J AU Robertson, B Myers, G Howard, C Brettin, T Bukh, J Gaschen, B Gojobori, T Maertens, G Mizokami, M Nainan, O Netesov, S Nishioka, K Shin-i, T Simmonds, P Smith, D Stuyver, L Weiner, A AF Robertson, B Myers, G Howard, C Brettin, T Bukh, J Gaschen, B Gojobori, T Maertens, G Mizokami, M Nainan, O Netesov, S Nishioka, K Shin-i, T Simmonds, P Smith, D Stuyver, L Weiner, A TI Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization SO ARCHIVES OF VIROLOGY LA English DT News Item ID ENTIRE NUCLEOTIDE-SEQUENCE; COMPLETE CODING SEQUENCE; MAJOR GENETIC GROUPS; NON-B HEPATITIS; NON-A; PHYLOGENETIC ANALYSIS; EVOLUTIONARY ANALYSIS; PREDOMINANT GENOTYPE; GENOMIC ORGANIZATION; DISTINCT GENOTYPES AB This paper presents a summary of the recommendations that were formulated for the purposes of unifying the nomenclature for hepatitis C virus (HCV), based upon guidelines of the International Committee on Virus Taxonomy (ICTV), and provides guidelines for the incorporation of sequence data into an HCV database that will be available to researchers through the internet, Based upon the available data, the genus Hepacivirus should be regarded as comprising a single species with HCV-1 as the prototype. All currently known isolates of HCV can be divided into six phylogenetically distinct groups, and we recommend that these groups are described as clades 1 to 6. Whether or not these should be regarded as different species within the Hepacivirus,genus requires additional clinical, virological, and immunological information. Clades 1, 2, 4, and 5 would correspond to genotype 1, 2, 4, and 5 while clade 3 would comprise genotype 3 and genotype 10, and clade 6 comprise genotypes 6, 7, 8, 9, and II. We propose that existing subtype designations are reassigned within these clades based upon publication priority, the existence of a complete genome sequence and prevalence. The assignment of isolates to new clades and subtypes should be confined to isolates characterized from epidemiologically unlinked individuals. Comparisons should be based on nucleotide sequences of at least two coding regions and preferably of complete genome sequences, and should be based on phylogenetic analysis rather than percent identity. A forum for discussion and contributions to these recommendations will be made available at the international HCV database at http://s2as02.genes.nig.ac.jp. C1 Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Hepatitis Branch, Atlanta, GA 30333 USA. Univ Calif Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. Univ London Royal Vet Coll, London, England. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 411, Japan. Hepatitis Program, Ghent, Belgium. Nagoya City Univ, Sch Med, Dept Med 2, Nagoya, Aichi, Japan. State Res Ctr Virol & Biotechnol Vector, Novosibirsk, Russia. Viral Hepatitis Res Fdn Japan, Tokyo, Japan. Univ Edinburgh, Dept Med Microbiol, Edinburgh, Midlothian, Scotland. Chiron Corp, Emeryville, CA 94608 USA. RP Robertson, B (reprint author), Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Hepatitis Branch, Atlanta, GA 30333 USA. RI Netesov, Sergey/A-3751-2013 OI Netesov, Sergey/0000-0002-7786-2464 NR 59 TC 340 Z9 361 U1 1 U2 14 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1998 VL 143 IS 12 BP 2493 EP 2503 DI 10.1007/s007050050479 PG 11 WC Virology SC Virology GA 166PR UT WOS:000078586500020 PM 9930205 ER PT J AU Katusic, ZS Stelter, A Milstien, S AF Katusic, ZS Stelter, A Milstien, S TI Cytokines stimulate GTP cyclohydrolase I gene expression in cultured human umbilical vein endothelial cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE nitric oxide; tetrahydrobiopterin; tumor necrosis factor-alpha; interferon-gamma; interleukin-1 beta ID NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; MESSENGER-RNA; TETRAHYDROBIOPTERIN LEVELS; CEREBRAL-ARTERIES; BIOSYNTHESIS; BIOPTERIN; FORMS AB In vascular endothelial cells, tetrahydrobiopterin serves as an essential cofactor required for enzymatic activity of nitric oxide synthase. GTP cyclohydrolase I is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. Previous studies have demonstrated that proinflammatory cytokines stimulate production of tetrahydrobiopterin in endothelial cells. Long-term regulation of GTP cyclohydrolase I gene expression in endothelium has not been studied. The present study was designed to determine whether the cytokines tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma), and interleukin-1 beta (IL-1 beta) stimulate tetrahydrobiopterin synthesis by increasing expression of GTP cyclohydrolase I mRNA in endothelial cells. The relative reverse transcription polymerase chain reaction was used to quantify expression of GTP cyclohydrolase I mRNA in cultured human umbilical vein endothelial cells. Nuclear run-on assay was performed to determine the transcription rate of GTP cyclohydrolase I gene. GTP cyclohydrolase I enzymatic activity and production of tetrahydrobiopterin were measured in cell extracts. After incubation with TNF-alpha (2 mu g/mL), INF-gamma (200 U/mL), and IL-1 beta (5 U/mL) for 24 hours, significantly increased expression of GTP cyclohydrolase I mRNA was detected. Cytokines increased the transcription rate of GTP cyclohydrolase I 3.6-fold. This increase was associated with increased GTP cyclohydrolase I enzymatic activity and elevation of intracellular levels of tetrahydrobiopterin. An RNA synthesis inhibitor, actinomycin D (2 mu g/mL), inhibited cytokine-induced expression of GTP cyclohydrolase I gene. A protein synthesis inhibitor, cycloheximide (0.5 mu g/mL), did not affect expression of GTP cyclohydrolase I mRNA but blocked the increase in enzyme activity, as well as production of tetrahydrobiopterin. Incubation of endothelial cells for 24 hours in the presence of 8-bromoadenosine 3':5'-cyclic monophosphate (10(-3) mol/L) did not affect expression of GTP cyclohydrolase I mRNA. These results demonstrate that in vascular endothelial cells, cytokines increase production of tetrahydrobiopterin by stimulating expression of GTP cyclohydrolase I gene. This effect is apparently due to increased transcription rather than stabilization of mRNA. Regulation of GTP cyclohydrolase I gene expression by cytokines may play an important role in control of endothelial nitric oxide synthesis. C1 Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA. NIMH, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Katusic, ZS (reprint author), Mayo Clin & Mayo Fdn, Dept Anesthesiol, 200 1St St SW, Rochester, MN 55905 USA. FU NHLBI NIH HHS [HL-53542] NR 20 TC 66 Z9 67 U1 0 U2 2 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 JAN PY 1998 VL 18 IS 1 BP 27 EP 32 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YR524 UT WOS:000071503900005 PM 9445252 ER PT J AU Mojcik, CF Shevach, EM AF Mojcik, CF Shevach, EM TI Adhesion molecules at the synovial level in rheumatoid arthritis: comment on the review article by Mojcik and Shevach - Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID PULSE METHYLPREDNISOLONE THERAPY; INFLAMMATORY INDEXES; PERIPHERAL-BLOOD; IMMUNE; FLUID C1 Bayer Pharmaceut, W Haven, CT 06516 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Mojcik, CF (reprint author), Bayer Pharmaceut, W Haven, CT 06516 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 1998 VL 41 IS 1 BP 186 EP 186 PG 1 WC Rheumatology SC Rheumatology GA YQ737 UT WOS:000071418200030 ER PT B AU Humphrey, SM AF Humphrey, SM BE Preston, CM TI A new approach to automatic indexing using journal descriptors SO ASIS '98 - PROCEEDINGS OF THE 61ST ASIS ANNUAL MEETING, VOL 35, 1998: INFORMATION ACCESS IN THE GLOBAL INFORMATION ECONOMY SE PROCEEDINGS OF THE ASIS ANNUAL MEETINGS LA English DT Proceedings Paper CT 61st Annual Meeting of the American-Society-for-Information-Science (ASIS) CY OCT 25-29, 1998 CL PITTSBURGH, PA SP Amer Soc Informat Sci C1 Natl Lib Med, Bethesda, MD USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA BN 1-57387-066-8 J9 P ASIS ANN PY 1998 VL 35 BP 496 EP 500 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA BP68P UT WOS:000085857900046 ER PT S AU Powell, DJ Bur, D Wlodawer, A Gustchina, A Dunn, BM Kay, J AF Powell, DJ Bur, D Wlodawer, A Gustchina, A Dunn, BM Kay, J BE James, MNG TI The aspartic proteinase from equine infectious anaemia virus SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID ANEMIA VIRUS; EXPRESSION; INHIBITOR C1 Univ Wales, Sch Mol & Med Biosci, Cardiff CF1 3US, S Glam, Wales. F Hoffmann La Roche AG, CH-4070 Basel, Switzerland. NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Florida, Sch Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Powell, DJ (reprint author), Univ Wales, Sch Mol & Med Biosci, Cardiff CF1 3US, S Glam, Wales. FU NIAID NIH HHS [AI 18571] NR 8 TC 0 Z9 0 U1 1 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 41 EP 45 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400005 PM 9561197 ER PT S AU Wilson, SI Phylip, LH Gulnik, SV Mills, JS Bur, D Dunn, BM Kay, J AF Wilson, SI Phylip, LH Gulnik, SV Mills, JS Bur, D Dunn, BM Kay, J BE James, MNG TI Sensitivity to inhibition and catalytic efficiency of HIV proteinase mutants SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID PROTEASE INHIBITORS; RESISTANCE; MUTATIONS C1 Univ Wales, Sch Mol & Med Biosci, Cardiff CF1 3US, S Glam, Wales. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Roche Prod Ltd, Res Ctr, Welwyn Garden City AL7 3AY, Herts, England. F Hoffmann La Roche AG, CH-4070 Basel, Switzerland. Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Wilson, SI (reprint author), Univ Wales, Sch Mol & Med Biosci, Cardiff CF1 3US, S Glam, Wales. FU NIAID NIH HHS [AI-28571] NR 9 TC 0 Z9 0 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 85 EP 89 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400011 PM 9561203 ER PT S AU Gustchina, EA Majer, P Rumsh, LD Ginodman, LM Andreeva, NS AF Gustchina, EA Majer, P Rumsh, LD Ginodman, LM Andreeva, NS BE James, MNG TI Post X-ray crystallographic studies of chymosin specificity - The role of histidine-proline cluster of kappa-casein in catalytic reactions SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID BOVINE CHYMOSIN; RESOLUTION C1 Russian Acad Sci, M Shemyakin & Y Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. Russian Acad Sci, W Engelhardt Inst Mol Biol, Moscow 117984, Russia. NCI, Struct Biochem Program, SAIC, FCRDC, Frederick, MD 21702 USA. RP Gustchina, EA (reprint author), Russian Acad Sci, M Shemyakin & Y Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. NR 8 TC 0 Z9 0 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 179 EP 184 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400024 PM 9561216 ER PT S AU Tarasova, NI Czerwinski, G Roberts, NB Lubkowski, J Sumpter, TL Green, BN Michejda, CJ AF Tarasova, NI Czerwinski, G Roberts, NB Lubkowski, J Sumpter, TL Green, BN Michejda, CJ BE James, MNG TI Mass spectrometry as a tool for studying the action of human aspartic proteases on peptides and proteins SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID GASTRIN C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Univ Liverpool, Royal Liverpool Hosp, Liverpool L69 3BX, Merseyside, England. Micromass UK Ltd, Altrincham, England. RP Tarasova, NI (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 7 TC 3 Z9 3 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 201 EP 206 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400028 PM 9561220 ER PT S AU Bateman, KS Chernaia, MM Tarasova, NI James, MNG AF Bateman, KS Chernaia, MM Tarasova, NI James, MNG BE James, MNG TI Crystal structure of human pepsinogen A SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID 1.8-A RESOLUTION; REFINEMENT C1 Univ Alberta, Dept Biochem, MRC, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. NCI, Mol Aspects Drug Design Sect, ABL Basic Res Program, FCDRC, Frederick, MD 21702 USA. RP Bateman, KS (reprint author), Univ Alberta, Dept Biochem, MRC, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. NR 11 TC 11 Z9 12 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 259 EP 263 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400036 PM 9561228 ER PT S AU Khan, AR Chernaia, MM Tarasova, NI James, MNG AF Khan, AR Chernaia, MM Tarasova, NI James, MNG BE James, MNG TI Crystallographic studies of an activation intermediate of human gastricsin SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID HUMAN PROGASTRICSIN; CRYSTAL C1 Univ Alberta, Dept Biochem, MRC, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. NCI, Mol Aspects Drug Design Sect, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. RP Khan, AR (reprint author), Univ Alberta, Dept Biochem, MRC, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. EM michael.james@ualberta.ca; michael.james@ualberta.ca NR 12 TC 0 Z9 0 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 265 EP 270 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400037 PM 9561229 ER PT S AU Olsen, V Cawley, NX Loh, YP AF Olsen, V Cawley, NX Loh, YP BE James, MNG TI Yapsin1 - Structure, biosynthesis, and specificity SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID YEAST ASPARTIC PROTEASE-3; OPIOMELANOCORTIN-CONVERTING ENZYME; YAP3; PURIFICATION; PROTEINASES; PITUITARY; SITES C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A38, Bethesda, MD 20892 USA. EM ypl@codon.nih.gov NR 14 TC 1 Z9 1 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 315 EP 319 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400042 PM 9561234 ER PT S AU Silva, AM Lee, AY Erickson, JW Goldberg, DE AF Silva, AM Lee, AY Erickson, JW Goldberg, DE BE James, MNG TI Structural analysis of plasmepsin II - A comparison with human aspartic proteases SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID PLASMODIUM-FALCIPARUM; CRYSTAL-STRUCTURES; HEMOGLOBIN DEGRADATION; HUMAN RENIN; PROTEINASE; INHIBITION; EXPRESSION; PATHWAY; COMPLEX C1 NCI, SAIC, Struct Biochem Program, Frederick, MD 21702 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Silva, AM (reprint author), NCI, SAIC, Struct Biochem Program, Bldg 322,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO-74102]; NIAID NIH HHS [AI 37977] NR 15 TC 22 Z9 22 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 363 EP 373 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400051 PM 9561243 ER PT S AU Xie, D Gulnik, S Collins, L Gustchina, E Bhat, TN Erickson, JW AF Xie, D Gulnik, S Collins, L Gustchina, E Bhat, TN Erickson, JW BE James, MNG TI Thermodynamics and proton uptake for pepstatin binding to retroviral and eukaryotic aspartic proteases SO ASPARTIC PROTEINASES: RETROVIRAL AND CELLULAR ENZYMES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Aspartic Proteinases CY OCT 22-27, 1996 CL BANFF, CANADA SP Abbott Labs, Adv ChemTech Inc, Agouron Pharmaceut Inc, Bayer Corp, Beatrice Foods Inc, Beckman Instruments Inc, Biomega Boehringer Ingelheim Res Inc, Ciba Geigy Canada Ltd, Chiron Corp, Dupont Merck, Enraf Nonius Co, Genencor Int, Genentech Inc, Glaxo Wellcome Inc, Mississauga, Glaxo Wellcome Inc, San Francisco, Glaxo Wellcome Res & Dev, Stevenage, Hoffmann La Roche, Merck & Co Inc, Molec Simulat Inc, Pharmacia & Upjohn, Prot Engn Network Ctr Excellence, Schering Plough Res Inst, Scios Inc, Selectide Corp, Silicon Graph Inc, Vertex Pharmaceut Inc ID ISOTHERMAL TITRATION CALORIMETRY; HIV-1 PROTEASE; PLASMODIUM-FALCIPARUM; PROTEINASES; ENDOTHIAPEPSIN; INHIBITOR C1 NCI, SAIC Frederick, Struct Biochem Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Xie, D (reprint author), NCI, SAIC Frederick, Struct Biochem Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 20 TC 5 Z9 5 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 0-306-45809-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 436 BP 381 EP 386 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BK79N UT WOS:000073382400053 PM 9561245 ER PT S AU Santamarina-Fojo, S Hoeg, JM Brewer, HB AF Santamarina-Fojo, S Hoeg, JM Brewer, HB BE Jacotot, B Mathe, D Fruchart, JC TI Use of transgenic animal models to study enzymes involved in lipoprotein metabolism and atherosclerosis SO ATHEROSCLEROSIS XI SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 11th International Symposium on Atherosclerosis CY OCT 05-09, 1997 CL PARIS, FRANCE SP Int Atherosclerosis Soc, Bristol Myers Squibb, Merck & Co Inc, Novartis, Parke Davis, Sanofi Recherche DE atherosclerosis; high-density lipoproteins; lecithin cholesteryl acyltransferase; transgenic mice; transgenic rabbits AB Lecithin cholesteryl acyltransferase (LCAT) plays a major role in HDL metabolism by facilitating the esterification of free cholesterol present in circulating plasma lipoproteins. We have investigated the role that this enzyme plays in reverse cholesterol transport and the development of atherosclerosis by inducing the formation of aortic lesions using an atherogenic diet in transgenic mice and rabbits that overexpress human LCAT. Despite elevated plasma concentrations of HDL-cholesterol and apolipoprotein (apo) A-I, LCAT transgenic mice have enhanced diet-induced aortic atherosclerosis. In contrast, LCAT transgenic rabbits have increased plasma concentrations of HDL-cholesterol and apoA-I, reduced levels of apoB-containing lipoproteins and decreased aortic atherosclerosis. Reduced plasma concentrations of the proatherogenic apo-B-containing lipoproteins in rabbits but not in mice, as well as the presence of a "dysfunctional" HDL in LCAT transgenic mice may account for the differences in atherosclerosis between the two LCAT transgenic animal models. Our findings demonstrate the importance of LCAT in modulating the process of reverse cholesterol transport and atherosclerosis. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Santamarina-Fojo, S (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr Dr MSC 1666, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82651-3 J9 INT CONGR SER PY 1998 VL 1155 BP 11 EP 17 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BL30E UT WOS:000075036600003 ER PT S AU Wilson, PWF D'Agostino, RB Kannel, WB AF Wilson, PWF D'Agostino, RB Kannel, WB BE Jacotot, B Mathe, D Fruchart, JC TI Secular trends in cardiovascular risk factor levels: a Framingham perspective SO ATHEROSCLEROSIS XI SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 11th International Symposium on Atherosclerosis CY OCT 05-09, 1997 CL PARIS, FRANCE SP Int Atherosclerosis Soc, Bristol Myers Squibb, Merck & Co Inc, Novartis, Parke Davis, Sanofi Recherche DE blood pressure; cholesterol; coronary heart disease; obesity; smoking AB The purpose of this brief summary is to provide comparisons of risk-factor levels determined in 1966-1969 (original Framingham cohort) with levels measured in 1984-1988 (second generation Framingham offspring). Mean systolic pressure levels were lower in the second generation, diastolic-pressure levels were similar in each sample, and the proportion of persons on blood pressure therapy increased in both sexes. The fraction of persons reporting current cigarette smoking decreased and physical activity index was slightly higher, but mean body mass index levels were generally greater and a tendency toward overweight and severe overweight was very evident in men and women from the offspring sample. Total and LDL cholesterol levels were generally lower in the offspring, but there were no significant differences in mean triglycerides and HDL cholesterol compared to the cohort. Although coronary death rates have declined greatly in Framingham and the USA since 1970, evidence For a commensurate decrease in levels of coronary risk factors is less apparent, and differences in risk-factor levels account for only part of the decrease in coronary mortality. C1 NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. RP Wilson, PWF (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82651-3 J9 INT CONGR SER PY 1998 VL 1155 BP 659 EP 664 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BL30E UT WOS:000075036600083 ER PT S AU Cannon, RO AF Cannon, RO BE Jacotot, B Mathe, D Fruchart, JC TI Effects of estrogen on the endothelium in postmenopausal women: implications for atherosclerosis SO ATHEROSCLEROSIS XI SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 11th International Symposium on Atherosclerosis CY OCT 05-09, 1997 CL PARIS, FRANCE SP Int Atherosclerosis Soc, Bristol Myers Squibb, Merck & Co Inc, Novartis, Parke Davis, Sanofi Recherche DE coronary artery disease; fibrinolysis; hormones; nitric oxide C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr MSC-1650, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82651-3 J9 INT CONGR SER PY 1998 VL 1155 BP 817 EP 823 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BL30E UT WOS:000075036600103 ER PT S AU Hoeg, JM Hong, MK Vossoughi, J Mintz, GS Summers, RM Hoyt, RF Wolff, SD Leon, MB AF Hoeg, JM Hong, MK Vossoughi, J Mintz, GS Summers, RM Hoyt, RF Wolff, SD Leon, MB BE Jacotot, B Mathe, D Fruchart, JC TI Vascular endpoints for quantitating atherosclerosis for human gene therapy clinical trials SO ATHEROSCLEROSIS XI SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 11th International Symposium on Atherosclerosis CY OCT 05-09, 1997 CL PARIS, FRANCE SP Int Atherosclerosis Soc, Bristol Myers Squibb, Merck & Co Inc, Novartis, Parke Davis, Sanofi Recherche DE familial hypercholesterolemia; intravascular ultrasound; low-density lipoproteins; magnetic resonance imaging; ultrafast computerized tomography; vascular compliance AB Background. Gene therapy for atherosclerosis requires new, more sensitive and specific vascular wall endpoints. Using normal, mutant and transgenic rabbits, as well as patients homozygous for familial hypercholesterolemia, an array of candidate methods for use in gene therapy studies have been systematically investigated. Methods. Angiographic, intravascular ultrasound (IVUS), magnetic resonance imaging (MRI) and ultrafast computerized tomography (UFCT) studies were conducted in rabbits (WHHL) and patients homozygous for low-density lipoprotein receptor deficiency (FH). Results. Angiography cannot detect types I-V atherosclerosis in WHHL rabbits. However; type II-V lesions are detected and quantitated by intravascular ultrasound (IVUS) and are associated with marked changes in the vascular compliance; these changes were correlated with the mural cholesterol content (r = - 0.94; p<0.001). Homozygous FH patients had substantial, diffuse, calcific coronary atherosclerosis detected by UFCT and IVUS. As in the rabbit models, nonobstructing lesions defined by angiography were associated with both structural and functional changes defined by both MRI and IVUS. Conclusions. Direct quantitation of arterial wall thickness by IVUS, MRI and UFCT (as well as the quantitation of vascular compliance by MRI and US) provide more sensitive and specific methods for the evaluation of the efficacy of gene therapy to prevent and reverse atherosclerosis. C1 NHLBI, Sect Cell Biol, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hoeg, JM (reprint author), NHLBI, Sect Cell Biol, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr DR MSC 1666, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82651-3 J9 INT CONGR SER PY 1998 VL 1155 BP 1181 EP 1186 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BL30E UT WOS:000075036600156 ER PT J AU Burkhauser, RV Clark, R Suzman, R AF Burkhauser, RV Clark, R Suzman, R TI Symposium on work, retirement and wealth: Current data and future needs: an international perspective SO AUSTRALIAN JOURNAL ON AGEING LA English DT Article; Proceedings Paper CT XVIth Congress of the International-Association-of-Gerontology CY AUG 19-23, 1996 CL ADELAIDE, AUSTRALIA SP Novartis Pharma Inc, Novartis Fdn Gerontol Res, Commonwealth Govt Australia, Elderly Citizens Homes, Adelaide Bank Ltd, Int Assoc Gerontol AB This symposium brought together a unique set of scholars who are both actively involved in ageing research and in the creation of the new generation of multiperiod social science-based longitudinal datasets for research. The symposium provided a description of the new data and examples of its use with respect to the work, retirement and wealth of older persons. The datasets discussed included: the US Health and Retirement Study, the Netherlands Household Panel Study, the German Socioeconomic Panel, the US Panel Study of income Dynamics, and several East and Southeast Asian datasets. C1 Syracuse Univ, Ctr Policy Res, Syracuse, NY 13244 USA. N Carolina State Univ, Raleigh, NC 27695 USA. NIA, Bethesda, MD 20892 USA. RP Burkhauser, RV (reprint author), Syracuse Univ, Ctr Policy Res, 426 Eggers Hall, Syracuse, NY 13244 USA. RI Burkhauser, Richard/G-5403-2015 OI Burkhauser, Richard/0000-0003-4629-0253 NR 1 TC 0 Z9 0 U1 0 U2 2 PU COUNCIL AGEING PI VICTORIA PA LEVEL 2, 3 BOWEN CRESCENT, MELBOURNE, VICTORIA, 3004, AUSTRALIA SN 0726-4240 J9 AUST J AGEING JI Aust. J. Ageing PY 1998 VL 17 IS 1 SU S BP 11 EP 13 DI 10.1111/j.1741-6612.1998.tb00847.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZD663 UT WOS:000072709900005 ER PT J AU Dennerstein, L Feldman, S Murdaugh, C Rossouw, J Tennstedt, S AF Dennerstein, L Feldman, S Murdaugh, C Rossouw, J Tennstedt, S TI Gender and health issues in ageing SO AUSTRALIAN JOURNAL ON AGEING LA English DT Article; Proceedings Paper CT XVIth Congress of the International-Association-of-Gerontology CY AUG 19-23, 1996 CL ADELAIDE, AUSTRALIA SP Novartis Pharma Inc, Novartis Fdn Gerontol Res, Commonwealth Govt Australia, Elderly Citizens Homes, Adelaide Bank Ltd, Int Assoc Gerontol ID INFORMAL CARE; MENOPAUSE AB There are pronounced gender differences relating to health and ageing reflecting biological and social differences and transitions and adaption to these. The most obvious biological difference is that women have a finite length of reproductive functioning, the termination of which is marked by menopause. The menopausal transition has physical, psychological and sexual concomitants. Postmenopausal life is characterise by increased cardiovascular and osteoporotic risk. Interventions for these disorders have not been adequately evaluated. Men five on average about 7 years less than women in most developed countries. Women form the majority of carers. The most common cost of caring is social, a restriction in personal and leisure time, and is directly related to the amount of care provided. The negative health effects of caring are primarily psychological, not physical. Most of the widowed are women, An Australian study found that women widowed in the last 12 months had lower self-related health and were more Likely to report they were stressed about their health. Recently widowed women scored lower on all the subscales of the SF-36 and were also more likely to be taking medication for 'nerves' and 'medication to help you sleep'. Women widowed longer than 12 months did not score significantly differently than married women on these parameters. Widowed women reported more difficulty managing on their income than did married women, regardless of the length of widowhood. Widows also reported more stress with children and other family members than did married women. C1 Univ Melbourne, Dept Psychiat, Off Gender & Hlth, Parkville, Vic 3052, Australia. Univ Melbourne, Alma Unit Women & Ageing, Parkville, Vic 3052, Australia. Univ S Carolina, Coll Nursing, Columbia, SC 29208 USA. NIH, Bethesda, MD 20892 USA. RP Dennerstein, L (reprint author), Univ Melbourne, Dept Psychiat, Off Gender & Hlth, Parkville, Vic 3052, Australia. NR 10 TC 1 Z9 1 U1 1 U2 2 PU COUNCIL AGEING PI VICTORIA PA LEVEL 2, 3 BOWEN CRESCENT, MELBOURNE, VICTORIA, 3004, AUSTRALIA SN 0726-4240 J9 AUST J AGEING JI Aust. J. Ageing PY 1998 VL 17 IS 1 SU S BP 19 EP 21 DI 10.1111/j.1741-6612.1998.tb00851.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZD663 UT WOS:000072709900009 ER PT J AU Fozard, JL AF Fozard, JL TI Contributions of longitudinal studies to epidemiology and disease prevention: an overview SO AUSTRALIAN JOURNAL ON AGEING LA English DT Article; Proceedings Paper CT XVIth Congress of the International-Association-of-Gerontology CY AUG 19-23, 1996 CL ADELAIDE, AUSTRALIA SP Novartis Pharma Inc, Novartis Fdn Gerontol Res, Commonwealth Govt Australia, Elderly Citizens Homes, Adelaide Bank Ltd, Int Assoc Gerontol ID PROSTATE DISEASE; NATURAL-HISTORY AB Longitudinal studies characterise changes with respect to initial levels and rates of changes. They help to identify transitions between normal ageing and disease; to identify persons at risk for age associated diseases and to plan interventions. The future usefulness of longitudinal studies will depend increasingly on the preservation of biological specimens. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Fozard, JL (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. RI Fozard, James Leonard/B-3660-2009 NR 25 TC 0 Z9 0 U1 0 U2 0 PU COUNCIL AGEING PI VICTORIA PA LEVEL 2, 3 BOWEN CRESCENT, MELBOURNE, VICTORIA, 3004, AUSTRALIA SN 0726-4240 J9 AUST J AGEING JI Aust. J. Ageing PY 1998 VL 17 IS 1 SU S BP 22 EP 24 DI 10.1111/j.1741-6612.1998.tb00852.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZD663 UT WOS:000072709900010 ER PT J AU Wetle, T AF Wetle, T TI Challenges and directions for gerontological research beyond 2000 SO AUSTRALIAN JOURNAL ON AGEING LA English DT Article; Proceedings Paper CT XVIth Congress of the International-Association-of-Gerontology CY AUG 19-23, 1996 CL ADELAIDE, AUSTRALIA SP Novartis Pharma Inc, Novartis Fdn Gerontol Res, Commonwealth Govt Australia, Elderly Citizens Homes, Adelaide Bank Ltd, Int Assoc Gerontol ID FAMILIAL ALZHEIMERS-DISEASE; COMMUNITY; RISK; ONSET; GENE AB There is a world-wide demographic revolution taking place. The population is ageing, causing us to rethink health, disease and ageing globally. New strategies must be developed to provide medical and social services for the increasing numbers of older people. In addition we are challenged to expand our knowledge of causes of morbidity and mortality and to explore new strategies to prevent excess disability and promote the health span of older people world-wide. Increased effort in three promising areas of research will help us to reach this goal. These include research into reducing disability, increasing healthy Life span,and conquering Alzheimer's disease. Although major scientific advances have been made, there is still much to be done to understand the major causes of disability and to develop and implement preventive strategies to; decrease the incidence of excess disability. Promoting healthy life styles as well as understanding the biological bases of ageing and age-related diseases hold the key to increasing healthy life span. Alzheimer's disease is a major cause of disability, and while our understanding of Alzheimer's disease is expanding, continued efforts are necessary to conquer this devastating disease. The demographic revolution has caused us to rethink health, disease and ageing globally World-wide, epidemiologists are predicting a shift in the disease burden from infectious diseases prevalent in the developing world (eg. respiratory and diarrheal diseases) to the chronic diseases of more developed societies (eg. ischaemic heart disease, depression and cerebrovascular disease). The ageing of the population world-wide and the shift in the global burden of disease pose many challenges to research scientists, clinicians and policy makers, Not only will we need to develop new strategies to provide medical and social services for the increased numbers of older people, but we are also challenged to expand knowledge of the causes of morbidity and mortality among the old and to explore new strategies to prevent excess disability and promote the health span of people world-wide. C1 NIA, Bethesda, MD 20892 USA. RP Wetle, T (reprint author), NIA, Bldg 31 Room 5C35,31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA. EM WetleT@exmur.nia.nih.gov NR 16 TC 0 Z9 0 U1 1 U2 1 PU COUNCIL AGEING PI VICTORIA PA LEVEL 2, 3 BOWEN CRESCENT, MELBOURNE, VICTORIA, 3004, AUSTRALIA SN 0726-4240 J9 AUST J AGEING JI Aust. J. Ageing PY 1998 VL 17 IS 1 SU S BP 107 EP 110 DI 10.1111/j.1741-6612.1998.tb00879.x PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZD663 UT WOS:000072709900037 ER PT J AU Sun, D Emmert-Buck, MR Fox, PC AF Sun, D Emmert-Buck, MR Fox, PC TI Differential cytokine mRNA expression in human labial minor salivary glands in primary Sjogren's syndrome SO AUTOIMMUNITY LA English DT Article DE salivary gland; cytokine; molecular biology; Sjogren's syndrome; autoimmunity ID MESSENGER-RNA EXPRESSION; TUMOR-NECROSIS-FACTOR; STIMULATORY FACTOR-II; GROWTH-FACTOR-BETA; RHEUMATOID-ARTHRITIS; ALLERGIC ENCEPHALOMYELITIS; AUTOIMMUNE EXOCRINOPATHY; INTERLEUKIN-4 IL-4; INTERFERON-GAMMA; FACTOR-ALPHA AB Cytokines are known to be involved in a number of autoimmune conditions and are increasingly viewed as key components in numerous aspects of normal and abnormal cell functions. The purpose of the present study was to investigate possible immunopathogenic mechanisms within the labial minor salivary glands of patients with primary Sjogren's syndrome (pSS) by examining differential cytokine gene expression in individual cell populations (acini, ducts, or lymphoid cells). A cell-specific microdissection technique in combination with reverse transcription-polymerase chain reaction (RT-PCR) and Southern hybridization using P-32-labeled cytokine gene-specific probes was utilized to measure cytokine messenger RNA expression in individual cell populations of patients and healthy controls, mRNAs for interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGP-beta 1) mere detected in the epithelial cells (acini and ducts) and lymphoid cells of the labial minor salivary glands of pSS patients. The expression levels of these mRNAs in the epithelial cells were either up- or down-regulated by adjacent focal infiltrating lymphoid cells, mRNAs for all of the above cytokines, with the exception of IFN-gamma, mere detected in salivary tissues of healthy volunteers. The epithelial cells in the salivary glands are active participants in the autoimmune-mediated process of pSS, as evidenced by their ability to express a high frequency and wide variety of cytokines, The presence of an infiltrating lymphoid focus within the gland appeared to modulate cytokine gene expression by the salivary epithelial cells. 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 MSC1190, Bethesda, MD 20892 USA. NR 50 TC 44 Z9 46 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 1998 VL 28 IS 3 BP 125 EP + DI 10.3109/08916939808996281 PG 15 WC Immunology SC Immunology GA 142CY UT WOS:000077183400002 PM 9867125 ER PT J AU Peterson, CM Ahkavan, M Fernandez-Soto, ML Rowell, C Scott, BK Peterson, KP AF Peterson, CM Ahkavan, M Fernandez-Soto, ML Rowell, C Scott, BK Peterson, KP TI Dapsone at onset of diabetes lowers glycated hemoglobin and delays death in NOD mice SO AUTOIMMUNITY LA English DT Article DE autoimmune modulation; dapsone; diabetes prevention; NOD mouse ID ANTIINFLAMMATORY DRUGS; CONCANAVALIN-A; PREVENTION; MOUSE; INSULIN; MYELOPEROXIDASE; DESTRUCTION; NEUTROPHILS; DISEASE AB Dapsone (4,4'-diaminodiphenyl sulfone) is a compound that has a large clinical experience due to its antimicrobial effects against mycobacterium leprae, the causative agent of leprosy, It is increasingly used in a number of clinical situations where inflammation may play an ancillary role. An inhibitory effect of the drug or lack thereof in the cumulative incidence or propagation of diabetes mellitus in the NOD mouse has mechanistic as well as therapeutic implications. We previously showed that dapsone administered continuously as a percentage of food to NOD mice inhibits the cumulative incidence of diabetes in a dose dependent fashion. In the present experiment, female NOD litter mates were randomized to receive dapsone (0.001% w/w as a percentage of food) at onset of diabetes. There were no differences in weight, blood glucose, or glycated hemoglobin at 10 weeks of age among the animals that were ultimately to receive dapsone (n = 10), mouse chow alone (n = 9), or those who did not develop diabetes (n = 3), The mean time to onset of diabetes, mean blood glucose at onset, and mean glycated hemoglobin at onset did not differ between animals who did or did not receive dapsone, Animals receiving dapsone had significantly (p less than or equal to 0.03) lower glycated hemoglobin at weeks 2, 3, and 4 following the onset of diabetes and lived significantly longer following diagnosis of diabetes (7 vs. 4 weeks, p < 0.05). In conclusion, dapsone modulates the progression of autoimmune diabetes in the NOD mouse even when administered after the initiation of hyperglycemia. C1 Sansum Med Res Fdn, Santa Barbara, CA 93105 USA. RP Peterson, CM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, Rm 10158,6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA. RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 NR 23 TC 4 Z9 4 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 1998 VL 28 IS 3 BP 157 EP 161 DI 10.3109/08916939808996284 PG 5 WC Immunology SC Immunology GA 142CY UT WOS:000077183400005 PM 9867128 ER PT J AU Nishimura, Y Xu, T Johren, O Hauser, W Saavedra, JM AF Nishimura, Y Xu, T Johren, O Hauser, W Saavedra, JM TI The angiotensin AT(1) receptor antagonist CV-11974 regulates cerebral blood flow and brain angiotensin AT(1) receptor expression SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE cerebral blood flow; autoregulation; angiotensin II receptors; Wistar-Kyoto rats; spontaneously hypertensive rats (SHR); AT(1) receptor expression ID CONVERTING ENZYME; HYPERTENSIVE RATS; AUTOREGULATION; BINDING AB We studied cerebral blood flow autoregulation by laser Doppler flowmetry, and expression of brain angiotensin II AT(1) receptors by quantitative autoradiography, after administration of an angiotensin AT(1) receptor antagonist, CV-11974 (Candesartan, 0.5 or 1.0 mg/kg day) for two weeks via subcutaneously implanted osmotic pumps in adult normotensive Wistar Kyoto and spontaneously hypertensive male rats (SHR). In SHR, the autoregulation curve was shifted towards higher blood pressures, when compared with that of normotensive Wistar Kyoto rats. Administration of CV-11974 shifted the autoregulation curve toward lower blood pressures in both Wistar Kyoto and SHR, partially normalizing the autoregulation curve in SHR. CV-11974 treatment markedly decreased the expression of AT, receptors in Wistar Kyoto rats, both in areas outside the blood brain barrier (subfornical organ, 95 % decrease) and inside the blood brain barrier (nucleus of the tractus solitarius, 87 % decrease, and paraventricular nucleus, 96 % decrease). Our results demonstrate that blockade of AT(1) receptors tends to normalize the shift to higher pressures in the autoregulation curve:of genetically hypertensive rats, and has a profound modulatory role in brain angiotensin II AT(1) receptors. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr,Bldg 10-2D57, Bethesda, MD 20892 USA. RI Johren, Olaf/G-6967-2011 NR 14 TC 21 Z9 21 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PY 1998 VL 93 SU 2 BP 63 EP 68 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 138KJ UT WOS:000076970800013 PM 9833166 ER PT J AU Bhat, PV Bader, T Nettesheim, P Jetten, AM AF Bhat, PV Bader, T Nettesheim, P Jetten, AM TI Differentiation-dependent regulation of retinal dehydrogenase gene expression in the trachea SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article DE retinoic acid; retinal dehydrogenase; gene expression; tracheal epithelium ID ALDEHYDE DEHYDROGENASE; EPITHELIAL-CELLS; RAT-KIDNEY; ACID; OXIDATION; RETINOIDS; TISSUES AB Retinoic acid (RA), a metabolite of vitamin A, is known to be a key signaling molecule in regulating epithelial cell differentiation. We recently characterized and cloned a retinal dehydrogenase (RALDH) that catalyzes the oxidation of retinal to RA. In this study, we investigated the effects of retinoids on the level of RALDH mRNA and protein as well as RALDH activity in the trachea and cultured tracheal epithelial cells. Vitamin A deficiency induced squamous metaplasia in the tracheal epithelium and down-regulated RALDH expression. Supplementation of retinol and retinoic acid to vitamin A deficient rats restored the normal mucociliary epithelium and up-regulated the RALDH expression. In rat epithelial cells cultured in vitro, RAinhibited squamous differentiation and promoted mucociliary differentiation. Squamous differentiated cultures (RA-) expressed very low levels of RALDH mRNA, wheras mucociliary differentiated cultures (RA+) expressed high levels of RALDH mRNA. Retinal and retinol were poor inducers of mucociliary differentiation as well as RALDH expression. The RALDH expression paralleled the expression of the mucin-l gene in mucociliary cultures. These results suggest that the expression of RALDH is dependent on the differentiation state of the airway epithelium. C1 Univ Montreal, CHUM, Lab Nutr & Canc, Dept Med,Res Ctr, Montreal, PQ H2W 1T8, Canada. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Bhat, PV (reprint author), Univ Montreal, CHUM, Lab Nutr & Canc, Dept Med,Res Ctr, Hotel Dieu Pavil,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM bhatp@ere.umontreal.ca OI Jetten, Anton/0000-0003-0954-4445 NR 23 TC 9 Z9 9 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1998 VL 76 IS 1 BP 59 EP 62 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZY851 UT WOS:000074667900006 PM 9666306 ER PT J AU Xia, D Kim, H Yu, CA Yu, L Kachurin, A Zhang, L Deisenhofer, J AF Xia, D Kim, H Yu, CA Yu, L Kachurin, A Zhang, L Deisenhofer, J TI A novel electron transfer mechanism suggested by crystallographic studies of mitochondrial cytochrome bc1 complex SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 8th Fisher Winternational Symposium of the Canadian-Society-of-Biochemistry-and-Molecular-and-Cellular-Biology on Membrane Proteins in Health and Disease CY APR 02-05, 1998 CL BANFF, CANADA SP Canadian Soc Biochem & Molecular & Cellular Biol DE bc1 complex; electron transfer; structure; conformational change; inhibitor ID BOVINE HEART-MITOCHONDRIA; IRON-SULFUR PROTEIN; PROTONMOTIVE Q-CYCLE; C REDUCTASE; ENERGY TRANSDUCTION; RESPIRATORY-CHAIN; BC(1) COMPLEX; INHIBITORS; BINDING; TRANSLOCATION AB The crystal structure of bovine mitochondrial cytochrome bc1 complex, an integral membrane protein complex of 11 different subunits with a total molecular mass of 242 kDa, demonstrated a tightly associated dimer consisting of three major regions: a matrix region primarily made of subunits core1, core2, 6, and 9; a transmembrane-helix region of 26 helices in the dimer contributed by cytochrome b, cytochrome c1, the Rieske iron-sulfur protein (ISP), subunits 7, 10, and 11; and an intermembrane-space region composed of extramembrane domains of ISP, cytochrome c1, and subunit 8. The structure also revealed the positions of and distances between irons of prosthetic groups, and two symmetry related cavities in the transmembrane-helix region upon dimerization of the bc1 complex. Extensive crystallographic studies on crystals of bc1 complexed with inhibitors of electron transfer identified binding pockets for both Q(o) and Q(i) site inhibitors. Discrete binding sites for subtypes of Q(o) site inhibitors have been mapped onto the Q(o) binding pocket, and bindings of different subtypes of Q(o) site inhibitors are capable of inducing dramatic conformational changes in the extramembrane domain of ISP. A novel electron transfer mechanism for the bc1 complex consistent with crystallographic observations is discussed. C1 Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RP Xia, D (reprint author), NCI, Crystallog Univ, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 7 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1998 VL 76 IS 5 BP 673 EP 679 DI 10.1139/bcb-76-5-673 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197AR UT WOS:000080342900002 PM 10353699 ER PT J AU Kinsella, JL Heller, P Froehlich, JP AF Kinsella, JL Heller, P Froehlich, JP TI Na+/H+ exchanger: proton modifier site regulation of activity SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 8th Fisher Winternational Symposium of the Canadian-Society-of-Biochemistry-and-Molecular-and-Cellular-Biology on Membrane Proteins in Health and Disease CY APR 02-05, 1998 CL BANFF, CANADA SP Canadian Soc Biochem & Molecular & Cellular Biol DE Na+/H+ exchangers; oligomers; hysteresis ID H+ EXCHANGER; MEMBRANE; ISOFORMS; EXPRESSION; DEPENDENCE; MECHANISM; NHE-3; STATE AB The Na+/H+ exchangers (NHE1-6) are integral plasma membrane proteins that catalyze the exchange of extracellular Na+ for intracellular H+. In addition to Na+ and H+ transport sites, NHE has an intracellular allosteric H+ modifier site that increases exchange activity when occupied by H+. NHE activity is also subject to control by a variety of extrinsic factors including hormones, growth factors, cytokines, and pharmacological agents. Many of these factors, working through second messenger pathways acting directly or indirectly on NHE, regulate NHE activity by shifting the apparent affinity of the H+ modifier site to more alkaline or more acid pH. The underlying molecular mechanisms involved in the activation of NHE by the H+ modifier site are poorly understood at this time, but likely involve slow protein conformational changes within a NHE oligomer. In this paper, we present initial experiments measuring intracellular pH-dependent transition rates between active and inactive oligomeric conformations and describe how these transition rates may be important for overall regulation of NHE activity. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kinsella, JL (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 22 TC 28 Z9 29 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1998 VL 76 IS 5 BP 743 EP 749 DI 10.1139/bcb-76-5-743 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197AR UT WOS:000080342900010 PM 10353707 ER PT J AU Opdecamp, K Kos, L Arnheiter, H Pavan, WJ AF Opdecamp, K Kos, L Arnheiter, H Pavan, WJ TI Endothelin signalling in the development of neural crest-derived melanocytes SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article DE neural crest; melanocyte; endothelin; differentiation ID B RECEPTOR GENE; AVIAN EMBRYO; COAT COLOR; MUTATIONS; CELLS; MICROPHTHALMIA; MEGACOLON; DELETION; PROTEIN; CLONING AB In both mice and humans, mutations in the genes encoding the endothelin B receptor and its ligand endothelin 3 lead to deficiencies in neural crest-derived melanocytes and enteric neurons. The discrete steps at which endothelins exert their functions in melanocyte development were examined in mouse neural crest cell cultures. Such cultures, kept in the presence of fetal calf serum, gave rise to cells expressing the early melanoblast marker Dct even in the absence of the phorbol eater tetradecanoyl phorbol acetate (TPA) or endothelins. However, these early Dct(+) cells did not proliferate and pigmented cells never formed unless TPA or endothelins were added. In fact, endothelin 2 was as potent as TPA in promoting the generation of both Dct+ melanoblasts and pigmented cells, and endothelin 1 or endothelin 3 stimulated the generation of melanoblasts and of pigmented cells to an even greater extent. The inhibition of this stimulation by the selective endothelin B receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-alpha-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine) suggested that the three endothelins all signal through the endothelin B receptor. This receptor was indeed expressed in Dct(+) melanoblasts, in addition to cells lacking Dct expression. The results demonstrate that endothelins are potent stimulators of melanoblast proliferation and differentiation. C1 NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. NIH, Lab Genet Dis Res, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. RP Arnheiter, H (reprint author), NINDS, Lab Dev Neurogenet, NIH, Bldg 36,Room 5D06,36 Convent Dr,MSC-4160, Bethesda, MD 20892 USA. NR 32 TC 47 Z9 48 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1998 VL 76 IS 6 BP 1093 EP 1099 DI 10.1139/bcb-76-6-1093 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205XB UT WOS:000080844900017 PM 10392719 ER PT J AU Player, MR Xiao, W Cramer, H Torrence, PF AF Player, MR Xiao, W Cramer, H Torrence, PF TI Methods for the characterization of phosphatase-stabilized 2-5A-antisense chimeras SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ANTISENSE CHIMERAS; 2-5A ANTISENSE; RNA TARGET; PHOSPHOROTHIOATES; OLIGONUCLEOTIDES; REAGENT; ANALOGS AB We have developed chromatographic and spectrophotometric assays for determining the degree of thiolation in phosphatase-resistant 5'-monothiophosphate-capped 2-5A-antisense chimeras. Concomitantly, we have explored the reactivity of this 5'-monophosphorothioate moiety with reporter reagents such as 5-iodoacetomidofluorescein and 5,5'-dithiobis(2-nitrobenzoic acid). On the basis of these reactions, analyses for 5'-monothiophosphate-functionalized 2-5A-antisense chimeras were made possible. Kinetic experiments demonstrated that oligonucleotide backbone negative charge could retard mixed disulfide formation in the reaction of 5,5'-dithiobis(2-nitrobenzoic acid) with 5'-monothiophosphorylated 2-5A-antisense chimeras. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 22 TC 6 Z9 6 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1998 VL 9 IS 1 BP 137 EP 142 DI 10.1021/bc970157p PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA YR500 UT WOS:000071501500017 PM 9460557 ER PT J AU Rosen, LA Barber, I Lyle, DB AF Rosen, LA Barber, I Lyle, DB TI A 0.5 G, 60 Hz magnetic field suppresses melatonin production in pinealocytes SO BIOELECTROMAGNETICS LA English DT Article DE melatonin; magnetic fields; rat; single cells; gland dissociation ID 60-HZ ELECTRIC-FIELDS; RATS; EXPOSURE; GLAND AB The objective of this study was to develop a model for testing various hypotheses concerning possible mechanisms whereby electromagnetic fields might induce suppression of nighttime melatonin production in rodents. A published method for digesting freshly obtained pineal glands to the single cell level was modified, yielding better than 95% viability. An in vitro exposure facility developed for the Food and Drug Administration was used for 12-h overnight exposures of primary pinealocyte cultures to 0.05 mT, 60 Hz, vertical AC and 0.06 mu T, DC fields. After exposure, cells were separated from the supernatant by centrifugation. Supernatant melatonin was measured by ELISA assays. Data from 10 experiments demonstrated an average 46% reduction in norepinephrine-induced production of melatonin in the pinealocytes. The results support the hypothesis that EM exposure can produce pineal gland melatonin suppression by affecting individual cells. (C) 1998 Wiley-Liss, Inc.dagger. C1 NIH, Div Res Grants, Bethesda, MD 20892 USA. US FDA, Oak Ridge Natl Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rosen, LA (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 5116,MSC 7854, Bethesda, MD 20892 USA. NR 15 TC 25 Z9 28 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PY 1998 VL 19 IS 2 BP 123 EP 127 DI 10.1002/(SICI)1521-186X(1998)19:2<123::AID-BEM11>3.3.CO;2-H PG 5 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA YV446 UT WOS:000071825000011 PM 9492170 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI The Internet and the biologist SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NR 6 TC 4 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 1 EP 15 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200001 PM 9707924 ER PT J AU Ouellette, BFF AF Ouellette, BFF TI The GenBank sequence database SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID DATA-BANK; INFORMATION; BIOLOGY C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Ouellette, BFF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 16 EP 45 PG 30 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200002 PM 9707925 ER PT J AU Hogue, CWV Bryant, SH AF Hogue, CWV Bryant, SH TI Structure databases SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID RESOLUTION; ALIGNMENT; PROTEINS; FILE; BINDING; COMPLEX; ENTREZ; TOOL C1 Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Hogue, CWV (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. RI Hogue, Christopher/B-6726-2008 NR 34 TC 0 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 46 EP 73 PG 28 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200003 PM 9707926 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI Information retrieval from biological databases SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID TOOL C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 98 EP 120 PG 23 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200005 PM 9707928 ER PT J AU Ostell, JM Kans, JA AF Ostell, JM Kans, JA TI The NCBI data model SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Ostell, JM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 7 Z9 7 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 121 EP 144 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200006 PM 9707929 ER PT J AU Schuler, GD AF Schuler, GD TI Sequence alignment and database searching SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID ACID SUBSTITUTION MATRICES; SIMIAN SARCOMA-VIRUS; AMINO-ACID; STATISTICAL SIGNIFICANCE; SIMILARITY SEARCHES; PROTEIN BLOCKS; GROWTH-FACTOR; NUCLEIC-ACID; BLAST; GENE C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Schuler, GD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 43 TC 9 Z9 9 U1 3 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 145 EP 171 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200007 PM 9707930 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI Practical aspects of multiple sequence alignment SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID DATABASE; PROTEINS; BLOCKS C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NR 11 TC 13 Z9 14 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 172 EP 188 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200008 PM 9707931 ER PT S AU Hershkovitz, MA Leipe, DD AF Hershkovitz, MA Leipe, DD BE Baxevanis, AD Ouellette, BFF TI Phylogenetic analysis SO BIOINFORMATICS: A PRACTICAL GUIDE TO THE ANALYSIS OF GENES AND PROTEINS SE Methods of Biochemical Analysis LA English DT Review ID MULTIPLE SEQUENCE ALIGNMENT; DEPENDENT PERMUTATION TEST; MINIMUM-EVOLUTION TREES; MAXIMUM-LIKELIHOOD; INFERRING PHYLOGENIES; PROTEIN SEQUENCES; CONFIDENCE-LIMITS; RIBOSOMAL-RNA; DNA-SEQUENCES; BOOTSTRAP C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Hershkovitz, MA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 58 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0076-6941 BN 0-471-19196-5; 0-471-32441-8 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 189 EP 230 PG 42 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200009 PM 9707932 ER PT J AU Baxevanis, AD Landsman, D AF Baxevanis, AD Landsman, D TI Predictive methods using protein sequences SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review ID SECONDARY STRUCTURE PREDICTION; AMINO-ACID-SEQUENCE; IDENTIFICATION; RESOLUTION; IMPROVEMENTS; ALIGNMENTS; ALGORITHM; FAMILIES; DATABASE; SERVER C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NIH, Natl Ctr Biotechnol Informat, Computat Biol Branch, Natl Lib Med, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 42 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 246 EP 267 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200011 PM 9707934 ER PT J AU Kans, JA Ouellette, BFF AF Kans, JA Ouellette, BFF TI Submitting DNA sequences to the databases SO BIOINFORMATICS SE METHODS OF BIOCHEMICAL ANALYSIS LA English DT Review C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Kans, JA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0076-6941 J9 METHOD BIOCHEM ANAL PY 1998 VL 39 BP 319 EP 353 PG 35 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL71W UT WOS:000076427200014 PM 9707937 ER PT J AU Krasuski, JS Alexander, GE Horwitz, B Daly, EM Murphy, DGM Rapoport, SI Schapiro, MB AF Krasuski, JS Alexander, GE Horwitz, B Daly, EM Murphy, DGM Rapoport, SI Schapiro, MB TI Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls) SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; magnetic resonance imaging; hippocampus; amygdala; parahippocampal gyrus; entorhinal cortex; dementia ID CEREBRAL BLOOD-FLOW; CEREBROSPINAL-FLUID; HIPPOCAMPAL ATROPHY; MEMORY IMPAIRMENT; DEMENTIA; MRI; AMYGDALA; DIAGNOSIS; MEN; QUANTIFICATION AB Background: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. Methods: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment defined as greater than or equal to 20 on the Mini-Mental State Exam, and in 21 healthy age-and sex-matched controls. Results: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG, Discriminant function analysis using MRI volumes produced 94% correct group classification. Conclusions: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals. C1 NIA, Neurosci Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Krasuski, JS (reprint author), NIA, Neurosci Lab, Ctr Clin, NIH, Bldg 10,Rm 6C414,9000 Rockville Pike, Bethesda, MD 20892 USA. RI daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467 NR 49 TC 142 Z9 151 U1 1 U2 3 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 JAN 1 PY 1998 VL 43 IS 1 BP 60 EP 68 DI 10.1016/S0006-3223(97)00013-9 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YP635 UT WOS:000071298700009 PM 9442345 ER PT J AU Newbold, RR AF Newbold, RR TI Adverse effects of estrogenic compounds result from exposure during critical periods of development. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Toxicol Lab, Dev Endocrinol Sect, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1998 VL 58 SU 1 MA M29 BP 32 EP 33 PG 2 WC Reproductive Biology SC Reproductive Biology GA ZX708 UT WOS:000074546000039 ER PT J AU Kwon, S Lunn, RM O'Brien, DA Bell, DA Eddy, EM AF Kwon, S Lunn, RM O'Brien, DA Bell, DA Eddy, EM TI Molecular cloning of a putative membrane-associated progesterone receptor component. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1998 VL 58 SU 1 MA 22 BP 78 EP 78 PG 1 WC Reproductive Biology SC Reproductive Biology GA ZX708 UT WOS:000074546000068 ER PT J AU Hild-Petito, S Reel, JR Larner, JM Blye, RP AF Hild-Petito, S Reel, JR Larner, JM Blye, RP TI Mechanism of action of a male antifertility drug, CDB 4022 ([4 alpha RS,5SR,9 beta RS]-2-ethyl-2,3,4,4 alpha,5,9 beta-hexahydro-8-iodo-7-methyl-5-[4-carbomethoxyphenyl]-1H-indeno(1,2-c) pyridine-hydrochloride). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 BIOQUAL Inc, Rockville, MD USA. NICHD, Contracept & Reprod Hlth Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1998 VL 58 SU 1 MA 312 BP 169 EP 169 PG 1 WC Reproductive Biology SC Reproductive Biology GA ZX708 UT WOS:000074546000358 ER PT B AU Meltzer, PS Bittner, M Heiskanen, M Hoffman, T Chen, YD Trent, JM AF Meltzer, PS Bittner, M Heiskanen, M Hoffman, T Chen, YD Trent, JM BE Mihich, E Croce, C TI Use of cDNA microarrays to assess DNA gene expression patterns in cancer SO BIOLOGY OF TUMORS LA English DT Proceedings Paper CT 9th Annual Pezcoller Symposium on the Biology of Tumors CY JUN 04-07, 1997 CL ROVERETO, ITALY SP Pezcoller Fdn, Bank Cassa Risparmio Trento Rovereto, Municipal, Provincial, & Regional Adm C1 Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-45932-9 PY 1998 BP 109 EP 116 PG 8 WC Oncology; Genetics & Heredity; Immunology; Microbiology SC Oncology; Genetics & Heredity; Immunology; Microbiology GA BL93D UT WOS:000077190800010 ER PT J AU Castelli, J Wood, KA Youle, RJ AF Castelli, J Wood, KA Youle, RJ TI The 2-5A system in viral infection and apoptosis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE ribonuclease; apoptosis; interferon ID PROGRAMMED CELL-DEATH; DOUBLE-STRANDED-RNA; 28S RIBOSOMAL-RNA; INTERFERON-TREATED CELLS; ADENOVIRUS E1A PROTEINS; TUMOR-NECROSIS-FACTOR; ENCEPHALOMYOCARDITIS VIRUS; GENE-EXPRESSION; BHRF1 PROTEIN; MESSENGER-RNA AB The 2-5A system is an established endogenous antiviral pathway. Interferon treatment of cells leads to an increase in basal, but latent, levels of 2-5A-dependent RNase (RNase L) and the family of 2'-5' oligoadenylate sythetases (OAS). Double-stranded RNA, thought to be derived from viral replication intermediates, activates GAS. Activated OBS converts ATP into unusual short 2'-5' linked oligoadenylates called 2-5A [ppp5'(A2'p5')2A]. The 2-5A binds to and activates RNase L which cleaves single stranded RNA with moderate specificity for sites 3' of UpUp and UpAp sequences, and thus leads to degradation of cellular rRNA. During apoptosis, generalized cellular RNA degradation, distinct from the differential expression of mRNA species that may regulate specific gene expression during apoptosis, has been observed. The mechanism of RNA breakdown during apoptosis has been commonly considered a non-specific event that reflects the generalized shut down of translation and homeostatic regulation during cell death. Due to the similar RNA degradation that occurs during both apoptosis and viral infection we investigated the potential role of RNase L in apoptosis. To investigate whether RNase L activity could lead to apoptosis, NIH3T3 cells were transfected with a iac-inducible vector containing the human RNase L gene. Treatment of these cells with isopropylthiogalactoside (IPTG) caused loss of cell viability that was confirmed as an apoptotic cell death by morphological and biochemical criteria. Similarly, specific allosteric activation of endogenous RNase L by introduction of 2-5A directly into L929 cells also induced apoptosis. In L929 cells poly(I).poly(C) treatment in combination with interferon caused an increase in apoptosis whereas neither interferon or double stranded RNA alone altered cell viability. Therefore, increased expression or activation of RNase L causes apoptosis. Inhibition of RNase L, specifically with a dominant negative mutant, suppressed poly (I)Ypoly(C)-induced apoptosis in interferon-primed fibroblasts. Poliovirus, a picornovirus with a single-stranded RNA genome, causes apoptosis of HeLa cells. Expression of the dominant negative inhibitor of RNase L in HeLa prevented virus induced apoptosis and maintained cell viability. Thus, reduction or inhibition of RNase L activity prevents apoptosis. Both apoptosis and the 2-5A system can provide defense against viral infection in multicellular organisms by preventing production and therefore spread of progeny virus. RNase L appears to function in both mechanisms, therefore, initiation of apoptosis may be one mechanism for the antiviral activity of the 2-5A system. (C) 1998 Elsevier, Paris. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Trevigen Inc, Gaithersburg, MD 20877 USA. RP Castelli, J (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 47 TC 67 Z9 70 U1 1 U2 6 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PY 1998 VL 52 IS 9 BP 386 EP 390 DI 10.1016/S0753-3322(99)80006-7 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 151QU UT WOS:000077732700006 PM 9856285 ER PT J AU Kafadar, K Prorok, PC Smith, PJ AF Kafadar, K Prorok, PC Smith, PJ TI An estimate of the variance of estimators for lead time and screening benefit time in randomized cancer screening trials SO BIOMETRICAL JOURNAL LA English DT Article DE Kaplan-Meier estimate; survival curve; influence function; asymptotic variance; cancer screening; lead time ID SURVIVAL CURVES; LENGTH BIAS; MORTALITY AB Variance estimators are derived for estimators of the average lead time and average benefit time due to screening in a randomized screening trial via influence functions. The influence functions demonstrate that these estimators are asymptotically equivalent to the mean difference, between the study and control case groups, in the appropriate survival times. For estimating benefit time, the survival time is measured since start of study; for estimating lead time, the survival time is measured since time of diagnosis. Asymptotic variances of these estimators can be calculated in a straightforward manner from the influence functions, and these variances can be estimated from actual trial data. The performance of the variance estimators is assessed via a simulated screening trial. The situation involving censored data is also discussed. C1 Univ Colorado, Dept Math, Denver, CO 80217 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Maryland, Dept Math, College Pk, MD 20742 USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1998 VL 40 IS 7 BP 801 EP 821 DI 10.1002/(SICI)1521-4036(199811)40:7<801::AID-BIMJ801>3.0.CO;2-7 PG 21 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 140NJ UT WOS:000077093700003 ER PT J AU Guerrini, R Capasso, A Marastoni, M Bryant, SD Cooper, PS Lazarus, LH Temussi, PA Salvadori, S AF Guerrini, R Capasso, A Marastoni, M Bryant, SD Cooper, PS Lazarus, LH Temussi, PA Salvadori, S TI Rational design of dynorphin A analogues with delta-receptor selectivity and antagonism for delta- and kappa-receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE dynorphin; peptide synthesis; bioassays; opioid peptides; opioid receptors ID MOUSE VAS-DEFERENS; OPIOID RECEPTORS; A ANALOGS; DERMORPHIN ANALOGS; RAT-BRAIN; MORPHINE; BINDING; POTENT; MU; PEPTIDES AB Substitution of 1,2,3,4-tetrahydroisoquinoline-3-carboxyl acid (Tic) in place of Gly(2) in dynorphin A-(1-13)-NH(2) and -(1-11)-NH(2) (DYN) analogues (1 and 2) decreased the affinity to the kappa, delta, and mu receptors, and kappa selectivity. The analogue [D-Ala(2), des-Gly(3)]DYN (4), a chimera between deltorphin/dermorphin N-terminal tripeptide and DYN, was virtually inactive for kappa-sites while the affinities for delta- and mu-receptors remained essentially unchanged. The doubly substituted analogue [2',6'-dimethyl-L-tyrosine (Dmt(1))-Tic(2)]DYN (3) exhibited high delta-affnity (K(1) = 0.39 nM) while mu- and kappa-affinities were only an order of magnitude less (4-5 nM). Bioactivity of [Tic(2)]DYN peptides (1-3) on guinea-pig ileum and rabbit jejunum revealed potent delta- and kappa-antagonism, while the delta agonist potency of 4 was comparable to DYN. Thus, conversion from a kappa-agonist to antagonist occurred with the inclusion of Tic into DYN analogues, similar to the appearance of antagonist properties with delta- and mu-opioid agonists containing a Tic(2) residue. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Salerno, Sch Pharm, I-84084 Fisciano Salerno, Italy. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Naples Federico 2, Dept Chem, I-80134 Naples, Italy. RP Salvadori, S (reprint author), Univ Ferrara, Dept Pharmaceut Sci, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. OI CAPASSO, Anna/0000-0002-6579-7802; Guerrini, Remo/0000-0002-7619-0918 NR 49 TC 23 Z9 24 U1 0 U2 0 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 JAN PY 1998 VL 6 IS 1 BP 57 EP 62 DI 10.1016/S0968-0896(97)10008-6 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA ZG261 UT WOS:000072983300006 PM 9502105 ER PT J AU Ji, XH Karavitis, M Razynska, A Kwansa, H Vasquez, G Fronticelli, C Bucci, E Gilliland, GL AF Ji, XH Karavitis, M Razynska, A Kwansa, H Vasquez, G Fronticelli, C Bucci, E Gilliland, GL TI alpha-subunit oxidation in T-state crystals of a sebacyl cross-linked human hemoglobin with unusual autoxidation properties SO BIOPHYSICAL CHEMISTRY LA English DT Article DE cross-linked hemoglobin; protein crystallography; T-state hemoglobin; three-dimensional structure; circular dichroism; autoxidation ID X-RAY-DIFFRACTION; MACROMOLECULAR STRUCTURES; RESOLUTION; METHEMOGLOBIN; REFINEMENT; MECHANISM; MYOGLOBIN; BEHAVIOR; BINDING; OXYGEN AB In the crystal structure of human T-state hemoglobin with a sebacyl residue cross-linking the two beta-subunit Lys(82)'s (DecHb), the Fe atoms of the alpha-subunit hemes are found to be oxidized with a water molecule bound. The three-dimensional structure and heme geometries were compared to those of deoxyhemoglobin and other partially and fully oxidized hemoglobins [R. Liddington, Z. Derewenda, E. Dodson, R. Hubbard, G. Dodson, J. Mel. Biol. 228 (1992) 551]. The heme geometries of the alpha-subunits are consistent with those observed in oxidized structures, The proximal histidines of the cu-subunits move toward the heme plane shifting the F-helix and FG-corner ina manner observed for partially oxidized human hemoglobin. This supports the hypothesis that these perturbations may precede the T-to R-state transition, Circular dichroism studies comparing DecHb and natural human hemoglobin in the deoxy and CO ligated forms confirm that the conformations of the deoxy forms are identical, but the ligated forms have slight differences in the solution structures. DecHb is found to be more resistant to autoxidation than natural hemoglobin. The time course of autoxidation of DecHb shows that it is virtually absent for the first 1500 min followed by a rapid increase. Thus, the discovery of the oxidation of the cu-subunits in the deoxy-crystals is quite unexpected. The data confirm that ligation of the alpha-subunits precedes that of the beta-subunits. This may suggest a low ligand affinity of the alpha-diligated form of hemoglobin. (C) 1998 Elsevier Science B.V. C1 Univ Maryland, Sch Med, Dept Biol Chem, Baltimore, MD 21201 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIST, Rockville, MD 20850 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Bucci, E (reprint author), Univ Maryland, Sch Med, Dept Biol Chem, 108 N Greene St, Baltimore, MD 21201 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NHLBI NIH HHS [HLBI-48517] NR 37 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JAN 1 PY 1998 VL 70 IS 1 BP 21 EP 34 DI 10.1016/S0301-4622(97)00096-3 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA YU539 UT WOS:000071728000003 PM 9474760 ER PT J AU Zohar, O Ikeda, M Shinagawa, H Inoue, H Nakamura, H Elbaum, D Alkon, DL Yoshioka, T AF Zohar, O Ikeda, M Shinagawa, H Inoue, H Nakamura, H Elbaum, D Alkon, DL Yoshioka, T TI Thermal imaging of receptor-activated heat production in single cells SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; MUSCARINIC RECEPTORS; ANTAGONIST BINDING; TEMPERATURE; SUBTYPES; CALCIUM; AGONIST; MICROCALORIMETRY; HYDROLYSIS; RESOLUTION AB Changes in enthalpy (i.e., heat content) occur during the diverse intracellular chemical and biophysical interactions that take place in the life cycle of biological cells. Such changes have previously been measured for cell suspensions or cell-free biochemical extracts by using microcalorimetry, thermocouples, or pyroelectric films, all of which afford minimal spatial or temporal resolution. Here we present a novel thermal imaging method that combines both diffraction-limited spatial (similar to 300 nm) and sampling-rate-limited time resolution, using the temperature-dependent phosphorescence intensity of the rare earth chelate Eu-TTA (europium (III) thenoyltrifluoro-acetonate). With this thermosensitive dye, we imaged intracellular heat waves evoked in Chinese hamster ovary cells after activation of the metabotropic ml-muscarinic receptor, Past application of acetylcholine onto the cells evoked a biphasic heat wave that was blocked by atropine, and after a brief delay was followed by a calcium wave. Atropine applied by itself produced a monophasic heat wave in the cells, suggesting that its interactions with the receptor activate some intracellular metabolic pathways. The thermal imaging technique introduced here should provide new insights into cellular functions by resolving the location, kinetics, and quantity of intracellular heat production. C1 NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. Waseda Univ, Sch Human Sci, Dept Mol Neurobiol, Saitama 359, Japan. PAN, Nenski Inst Expt Biol, Warsaw, Poland. RP Zohar, O (reprint author), NINDS, Lab Adapt Syst, 36 Convent Dr MSC 4124, Bethesda, MD 20892 USA. EM zohar@codon.nih.gov NR 39 TC 90 Z9 90 U1 3 U2 23 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1998 VL 74 IS 1 BP 82 EP 89 PG 8 WC Biophysics SC Biophysics GA ZL046 UT WOS:000073393400010 PM 9449312 ER PT J AU Zhang, JQ Weisberg, A Horowits, R AF Zhang, JQ Weisberg, A Horowits, R TI Expression and purification of large nebulin fragments and their interaction with actin SO BIOPHYSICAL JOURNAL LA English DT Article ID SKELETAL-MUSCLE SARCOMERE; THIN-FILAMENTS; PROTEIN; SEQUENCE; MYOSIN; ARCHITECTURE; PHALLOIDIN; TEMPLATE; CLONING; REPEATS AB cDNA clones encoding mouse skeletal muscle nebulin were expressed in Escherichia coli as thioredoxin fusion proteins and purified in the presence of 6 M urea. These fragments, called 7a and 8c, contain 28 and 19 of the weakly repeating similar to 35-residue nebulin modules, respectively. The nebulin fragments are soluble at extremely high pH, but aggregate when dialyzed to neutral pH, as assayed by centrifugation at 16,000 x g. However, when mixed with varying,amounts of G-actin at pH 12 and then dialyzed to neutral pH, the nebulin fragments are solubilized in a concentration-dependent manner, remaining in the supernatant along with the monomeric actin. These results show that interaction with G-actin allows the separation of insoluble nebulin aggregates from soluble actin-nebulin complexes by centrifugation. We used this property to assay the incorporation of nebulin fragments into preformed actin filaments. Varying amounts of aggregated nebulin were mixed with a constant amount of F-actin at pH 7.0. The nebulin aggregates were pelleted by centrifugation at 5200 x g, whereas the actin filaments, including incorporated nebulin fragments, remained in the supernatant. Using this assay, we found that nebulin fragments 7a and 8c bound to actin filaments with high affinity. Immunofluorescence and electron microscopy of the actin-nebulin complexes verified that the nebulin fragments were reorganized from punctate aggregates to a filamentous form upon interaction with F-actin. in addition, we found that fragment 7a binds to F-actin with a stoichiometry of one nebulin module per actin monomer, the same stoichiometry we found in vivo. In contrast, 8c binds to F-actin with a stoichiometry of one module per two actin monomers. These data indicate that 7a can be incorporated into actin filaments to the same extent found in vivo, and suggest that shorter fragments may not bind actin filaments in the same way as the native nebulin molecule. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Horowits, R (reprint author), NIAMSD, NIH, Bldg 6,Room 408,MSC 2751, Bethesda, MD 20892 USA. NR 27 TC 18 Z9 18 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1998 VL 74 IS 1 BP 349 EP 359 PG 11 WC Biophysics SC Biophysics GA ZL046 UT WOS:000073393400033 PM 9449335 ER PT J AU Schuck, P MacPhee, CE Howlett, GJ AF Schuck, P MacPhee, CE Howlett, GJ TI Determination of sedimentation coefficients for small peptides SO BIOPHYSICAL JOURNAL LA English DT Article ID BOUNDARY ANALYSIS AB Direct fitting of sedimentation velocity data with numerical solutions of the Lamm equations has been exploited to obtain sedimentation coefficients for single solutes under conditions where solvent and solution plateaus are either not available or are transient, The calculated evolution was initialized with the first experimental scan and nonlinear regression was employed to obtain best-fit values for the sedimentation and diffusion coefficients. General properties of the Lamm equations as data analysis tools were examined. This method was applied to study a set of small peptides containing amphipathic heptad repeats with the general structure Ac-YS-(AKEAAKE)(n)GAR-NH2, n = 2, 3, or 4. Sedimentation velocity analysis indicated single sedimenting species with sedimentation coefficients (s(20,w) values) of 0.37, 0.45, and 0.52 S, respectively, in good agreement with sedimentation coefficients predicted by hydrodynamic theory. The described approach can be applied to synthetic boundary and conventional loading experiments, and can be extended to analyze sedimentation data for both large and small macromolecules in order to define shape, heterogeneity, and state of association. C1 NIH, ORS, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Parkville, Vic 3052, Australia. RP Schuck, P (reprint author), NIH, ORS, Biomed Engn & Instrumentat Program, Bldg 13,Rm 3N17, Bethesda, MD 20892 USA. OI MacPhee, Cait/0000-0001-8313-8387; Schuck, Peter/0000-0002-8859-6966 NR 29 TC 61 Z9 61 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1998 VL 74 IS 1 BP 466 EP 474 PG 9 WC Biophysics SC Biophysics GA ZL046 UT WOS:000073393400045 PM 9449347 ER PT J AU Burke, TR Zhang, ZY AF Burke, TR Zhang, ZY TI Protein-tyrosine phosphatases: Structure, mechanism, and inhibitor discovery SO BIOPOLYMERS LA English DT Review DE protein-tyrosine phosphatases; protein-tyrosine kinase; cell functions; protein-tyrosine phosphatase inhibitors; protein-tyrosine phosphatase catalysis ID PROSTATIC ACID-PHOSPHATASE; DUAL-SPECIFICITY PHOSPHATASE; SERINE THREONINE PHOSPHATASES; TRANSITION-STATE STRUCTURES; LEUKOCYTE-COMMON ANTIGEN; SOLID-PHASE SYNTHESIS; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; CRYSTAL-STRUCTURE; CATALYTIC MECHANISM AB Protein-tyrosine kinases (PTKs) and their associated signaling pathways are crucial for the regulation of numerous cell functions including growth, mitogenesis, motility, cell-cell interactions, metabolism, gene transcription, and the immune response. Since tyrosine phosphorylation is reversible and dynamic in vivo, the phosphorylation states of proteins are governed by the opposing actions of PTKs and protein-tyrosine phosphatases (PTPs). In this light, both PTKs and PTPs play equally important roles in signal transduction in eukaryotic cells, and comprehension of mechanisms behind the reversible pTyr-dependent modulation of protein function and cell physiology must necessarily encompass the characterization of PTPs as well as PTKs. In spite of the large number of PTPs identified to date and the emerging role played by PTPs in disease, a detailed understanding of the role played by PTPs in signaling pathways has been hampered by the absence of PTP-specific agents. Such PTP-specific inhibitors could potentially serve as useful tools in determining the physiological significance of protein tyrosine phosphorylation in complex cellular signal transduction pathways and may constitute valuable therapeutics in the treatment of several human diseases. The goal of this review is therefore to summarize current understandings of PTP structure and mechanism of catalysis and the relationship of these to PTP inhibitor development The review is organized such that enzyme structure is covered first, followed by mechanisms of catalysis then PTP inhibitor development. In discussing PTP inhibitor development, nonspecific inhibitors and those obtained by screening methods are initially presented with the focus then shifting to inhibitors that utilize a more structure-based rationale. (C) 1998 John Wiley & Sons, Inc. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 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 185 TC 141 Z9 143 U1 5 U2 18 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 1998 VL 47 IS 3 BP 225 EP 241 DI 10.1002/(SICI)1097-0282(1998)47:3<225::AID-BIP3>3.0.CO;2-O PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 136CR UT WOS:000076841000003 PM 9817026 ER PT J AU Sperbeck, SJ Wistow, GJ AF Sperbeck, SJ Wistow, GJ TI pBendBlue: Modification of the pBend system for color selectability SO BIOTECHNIQUES LA English DT Article ID DNA C1 NEI, NIH, Bethesda, MD 20892 USA. RP Wistow, GJ (reprint author), NEI, NIH, Room 331,Bldg 6, Bethesda, MD 20892 USA. NR 4 TC 8 Z9 9 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1998 VL 24 IS 1 BP 66 EP + PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ698 UT WOS:000071414300013 PM 9454955 ER PT J AU Rajendrakumar, GV Adhya, S AF Rajendrakumar, GV Adhya, S TI Fluorescence-based protein footprinting using histidine-tagged protein SO BIOTECHNIQUES LA English DT Article ID GENE ACTIVATOR PROTEIN; COLI RNA-POLYMERASE; ESCHERICHIA-COLI; DNA-BINDING; CAP; DETERMINANTS; FRAGMENTS; SIGMA(70); STABILITY; SUBUNITS AB We describe a procedure for protein footprinting to identify the region(s) of a protein that interacts with a ligand. The method utilized the affinity of a stretch of histidine residues cloned into the protein to metal-chelated resin. After limited protease digestion, the histidine-tagged end fragments were separated by the resin and labeled with a fluorescein derivative. Resolving the labeled digestion products on a denaturing polyacrylamide gel and visualizing the peptides using a FluorImager(TM) provided a way to identify the protease target sites that were protected from digestion because of interaction with DNA. The protection experiments would be applicable not only to detect direct contact sites but also sites allosterically altered by ligand binding. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, NIH, Bldg 37,Room 2E16, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 26 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1998 VL 24 IS 1 BP 110 EP 115 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ698 UT WOS:000071414300021 PM 9454962 ER PT J AU Onodera, M Ariga, T Kawamura, N Kobayashi, I Ohtsu, M Yamada, M Tame, A Furuta, H Okano, M Matsumoto, S Kotani, H McGarrity, GJ Blaese, RM Sakiyama, Y AF Onodera, M Ariga, T Kawamura, N Kobayashi, I Ohtsu, M Yamada, M Tame, A Furuta, H Okano, M Matsumoto, S Kotani, H McGarrity, GJ Blaese, RM Sakiyama, Y TI Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; BLOOD LYMPHOCYTES; MESSENGER-RNA; BONE-MARROW; CELL LINES; SEQUENCE; THERAPY; CDNA; HETEROGENEITY; EXPRESSION AB Ten patients with adenosine deaminase deficiency (ADA(-)) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990, We describe a Japanese ADA-severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN, The percentage of peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% during the 12 months since the fourth infusion. ADA enzyme activity in the patient's circulating T cells, which was only marginally detected before gene transfer, increased to levels comparable to those of a heterozygous carrier individual and was associated with increased T-lymphocyte counts and improvement of the patient's immune function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA-SCID. (C) 1998 by The American Society of Hematology. C1 Hokkaido Univ, Sch Med, Dept Pediat, Kita Ku, Sapporo, Hokkaido 060, Japan. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Hlth Sci Univ Hokkaido, Inst Med Sci, Sapporo, Hokkaido, Japan. Genet Therapy Inc, Gaithersburg, MD USA. RP Sakiyama, Y (reprint author), Hokkaido Univ, Sch Med, Dept Pediat, Kita Ku, North 15,West 7, Sapporo, Hokkaido 060, Japan. RI Ariga, Tadashi/A-4252-2012; Kobayashi, Ichiro/G-8638-2012 NR 33 TC 100 Z9 104 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 30 EP 36 PG 7 WC Hematology SC Hematology GA YN358 UT WOS:000071160100004 PM 9414266 ER PT J AU Passweg, JR Tiberghien, P Cahn, JY Vowels, MR Camitta, BM Gale, RP Herzig, RH Hoelzer, D Horowitz, MM Ifrah, N Klein, JP Marks, DI Ramsay, NKC Rowlings, PA Weisdorf, DJ Zhang, MJ Barrett, AJ AF Passweg, JR Tiberghien, P Cahn, JY Vowels, MR Camitta, BM Gale, RP Herzig, RH Hoelzer, D Horowitz, MM Ifrah, N Klein, JP Marks, DI Ramsay, NKC Rowlings, PA Weisdorf, DJ Zhang, MJ Barrett, AJ TI Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia SO BONE MARROW TRANSPLANTATION LA English DT Article DE ALL; bone marrow transplantation; graft-versus-leukemia; T lineage; B lineage ID BONE-MARROW TRANSPLANTATION; HOST-DISEASE; HUMAN RECIPIENTS; DONOR; CELLS; CLASSIFICATION; RECOGNITION; GENERATION; REACTIVITY; SURVIVAL AB T and B lineage ALL cells express different levels of HLA-class II antigens, which may serve as targets for graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL), The object of this study was to determine whether GVL effects after HLA-identieal sibling bone marrow transplantation differed in T and B lineage ALL. We studied 1132 patients with ALL of T lineage (n = 416) or of B lineage (cALLa(+)) (n = 716) transplanted in first (n = 605) or second (n = 527) remission with bone marrow from an HLA-identical sibling donor, between 1982 and 1992, and reported to the IBMTR by 165 teams, Cox proportional hazards regression models were used to determine the relative risk (RR) of relapse in patients with acute (grades II-IV) or chronic GVHD vs patients without GVHD, Acute and chronic GVHD were considered as time-dependent covariates. Patients transplanted in first and second remission were analyzed separately, GVHD decreased relapse risks to a similar extent in T and B lineage ALL, For first remission transplants, relative risks of relapse for patients with vs those without GVHD was 0.34 for T lineage ALL and 0.44 for B lineage ALL. Corresponding relative risks in second remission transplants were 0.54 and 0.61, This study confirms earlier findings of an antileukemia effect of GVHD in ALL, This effect was similar in T lineage and B lineage ALL, despite probable differences in HLA-class II antigen expression. C1 Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Hlth Policy Inst, Milwaukee, WI 53226 USA. Etab Transfus Sanguine Franche Comte, Besancon, France. Hop Jean Minjoz, Serv Hematol, F-25030 Besancon, France. Prince Wales Childrens Hosp, Bone Marrow Transplant Unit, Randwick, NSW 2031, Australia. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Salick Hlth Care Inc, Div Bone Marrow & Stem Cell Transplantat, Los Angeles, CA USA. Univ Louisville, James Graham Brown Canc Ctr, Div Med Oncol Hematol, Louisville, KY 40292 USA. Univ Frankfurt, Zentrum Inneren Med, Dept Hematol, D-6000 Frankfurt, Germany. Serv Malad Sang, Angers, France. Hahnemann Univ, Bone Marrow Transplant Program, Philadelphia, PA USA. Univ Minnesota Hosp & Clin, Bone Marrow Transplant Program, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Hlth Policy Inst, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. FU NCI NIH HHS [P01-CA-40053] NR 27 TC 86 Z9 88 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 1998 VL 21 IS 2 BP 153 EP 158 DI 10.1038/sj.bmt.1701064 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA YZ151 UT WOS:000072225400008 PM 9489632 ER PT J AU Miller, DH Grossman, RI Reingold, SC McFarland, HF AF Miller, DH Grossman, RI Reingold, SC McFarland, HF TI The role of magnetic resonance techniques in understanding and managing multiple sclerosis SO BRAIN LA English DT Review DE magnetic resonance; multiple sclerosis ID ATTENUATED INVERSION-RECOVERY; MRI LESION LOAD; GADOLINIUM-ENHANCED MRI; CONVENTIONAL SPIN-ECHO; APPEARING WHITE-MATTER; ACUTE OPTIC NEURITIS; DISEASE-ACTIVITY; PULSE SEQUENCES; CLINICAL-APPLICATIONS; BRAIN MRI AB Magnetic resonance (MR) techniques have had a major impact in the last 10-15 years in understanding and managing multiple sclerosis. This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: (i) technical issues; (ii) role in diagnosis; (iii) natural history studies in understanding the disease; (iv) application in clinical trials. The theory and methodology of relevant technical issues is outlined in order to provide a framework with which to understand the potential and limitations of MR in addressing biological and clinical questions in multiple sclerosis. The principles underlying signal-to-noise and contrast-to-noise ratio are discussed, along with the techniques and clinical results for conventional and fast spin echo T-2-weighted imaging, fluid-attenuated inversion recovery, detection of blood-brain barrier break down and hypointense lesions on T-1-weighted images, magnetization transfer T-2 decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and quantification of lesion load and atrophy. MRI has an extremely valuable role in confirming the clinical diagnosis of multiple sclerosis. T-2-weighted brain imaging remains the standard diagnostic tool, but in some instances it is usefully complemented with gadolinium enhancement and spinal imaging. The caveat that the diagnosis of multiple sclerosis remains primarily a clinical one cannot be over-emphasized. Serial MRI studies have added much to our understanding of the natural history and pathophysiology of the disease. Blood-brain barrier breakdown is a consistent early feature of new lesion development in relapsing-remitting and secondary progressive multiple sclerosis, and this usually correlates with active inflammation and myelin breakdown. A number of the acute MR changes are reversible, but chronic persistent abnormalities in a number of MR parameters, such as reduced N-acetyl aspartate, low magnetization transfer ratios, atrophy and T-1-hypointensity, suggest the presence; of demyelination and/or axonal degeneration in many chronic lesions. The presence and extent of T-2-weighted MRI abnormalities at first presentation with a clinically isolated syndrome suggestive of demyelination strongly predicts the risk of developing clinically definite multiple sclerosis in the next few years. In established multiple sclerosis, however the correlations between T-2 abnormalities and disability are modest. This poor relationship partly relates to the discrepancy between lesion site and function in attempting to correlate locomotor disability with brain MRI findings. However the correlations between brain lesion load and cognitive dysfunction in multiple sclerosis, whilst more evident are still modest. A more important limitation is the low pathological specificity of abnormalities seen on T-2-weighted images. Stronger correlations have been found between disability and new putative MR markers for demyelination and/or axonal degeneration. Serial studies using multiple MR techniques are now needed to further clarify pathophysiological mechanisms in multiple sclerosis. Serial MR has become an important tool in monitoring treatment efficacy. It provides data which can be readily analysed in a blinded fashion and which directly inspects the pathological evolution; it also enables a rapid and sensitive measure of treatment outcome in early relapsing-remitting and secondary progressive disease. Because of the modest clinical correlations it is, however still appropriate that the definitive determinant of treatment efficacy remains a clinical one. Further work is needed to address issues of quality control in serial studies, statistical calculation of appropriate sample sizes, and optimization of the nature and frequency of MR outcomes measured. C1 Inst Neurol, Dept Clin Neurol, London WC1 3BG, England. Hosp Univ Penn, Philadelphia, PA 19104 USA. Natl Multiple Sclerosis Soc, New York, NY 10001 USA. NIH, Bethesda, MD 20892 USA. RP Miller, DH (reprint author), Inst Neurol, Dept Clin Neurol, Queen Sq, London WC1 3BG, England. NR 154 TC 406 Z9 411 U1 10 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1998 VL 121 BP 3 EP 24 DI 10.1093/brain/121.1.3 PN 1 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YU532 UT WOS:000071727300002 PM 9549485 ER PT J AU Lugaresi, E Montagna, P Tinuper, P Plazzi, G Gallassi, R Wang, TCL Markey, SP Rothstein, JD AF Lugaresi, E Montagna, P Tinuper, P Plazzi, G Gallassi, R Wang, TCL Markey, SP Rothstein, JD TI Endozepine stupor - Recurring stupor linked to endozepine-4 accumulation SO BRAIN LA English DT Article DE stupor; coma; benzodiazepine; endozepine; flumazenil ID BENZODIAZEPINE RECEPTOR LIGANDS; POSSIBLE INVOLVEMENT; BRAIN; SLEEPINESS; PLANTS; SYSTEM; COMA AB Recurring stupor can be caused by repeated metabolic, toxic or structural brain disturbances. Recently, cases of recurring stupor with fast EEG activity were shown to display increased endogenous benzodiazepine-like activity during the episodes of stupor. Patients with recurring stupor underwent extensive and toxicologic screening EEG and brain imaging. Endozepines and exogenously administered benzodiazepines were assayed in plasma and CSF by means of mass spectrometry. Flumazenil, a benzodiazepine antagonist was administered and the behavioural and EEG responses monitored. Treatment with oral flumazenil was attempted in selected cases. Twenty patients were found with recurring stupor. Episodes had begun between ages 18 and 67 years, and in nine patients, had disappeared spontaneously after 4-6 years with symptoms. Stupor lasted hours or days. Onset of the episodes and frequency were unpredictable. Patients were normal between attacks. Stupor was characterized by initial drowsiness, staggering and behavioural changes, followed by deep sleep and spontaneous recovery with post-ictal amnesia. Biochemical screening and brain imaging were always normal. Ictal EEG showed fast background activity, and flumazenil transiently awoke the patients and normalized the EEG. In the nine cases examined endozepine-4 levels were increased during the stupor. Oral flumazenil reduced the frequency of the attacks in three of these nine patients. Recurring episodes of stupor may be due to increased endozepine-4. We propose the term 'endozepine stupor' for such episodes. Endozepine-4 is an endogenous ligand for the benzodiazepine recognition site at the GABA(A) receptor with unknown molecular structure. C1 Univ Bologna, Inst Clin Neurol, Bologna, Italy. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Lugaresi, E (reprint author), Via Ugo Foscolo 7, I-40123 Bologna, Italy. RI rothstein, jeffrey/C-9470-2013; OI Plazzi, Giuseppe/0000-0002-1051-0472; Provini, Federica/0000-0001-9063-2658; tinuper, paolo/0000-0002-0588-3063 NR 30 TC 28 Z9 28 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1998 VL 121 BP 127 EP 133 DI 10.1093/brain/121.1.127 PN 1 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YU532 UT WOS:000071727300010 PM 9549493 ER PT S AU Elenkov, IJ AF Elenkov, IJ BE Oomura, Y Hori, T TI Neuroendocrine regulation of Th1/Th2 balance SO BRAIN AND BIODEFENCE SE TANIGUCHI SYMPOSIA ON BRAIN SCIENCES LA English DT Proceedings Paper CT 21st International Taniguchi Symposium on Brain Sciences on the Brain and the Biodefense System CY JAN 19-22, 1998 CL KYOTO, JAPAN C1 NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), NIAMS, Arthrit & Rheumatism Branch, NIH, 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 1013-2791 BN 3-8055-6764-2 J9 TANIG SYMP BRAIN SCI PY 1998 VL 21 BP 13 EP 26 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA BL78N UT WOS:000076722300002 ER PT S AU Quan, N AF Quan, N BE Oomura, Y Hori, T TI Brain cytokine expression in response to peripheral infection SO BRAIN AND BIODEFENCE SE TANIGUCHI SYMPOSIA ON BRAIN SCIENCES LA English DT Proceedings Paper CT 21st International Taniguchi Symposium on Brain Sciences on the Brain and the Biodefense System CY JAN 19-22, 1998 CL KYOTO, JAPAN C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Quan, N (reprint author), NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1013-2791 BN 3-8055-6764-2 J9 TANIG SYMP BRAIN SCI PY 1998 VL 21 BP 125 EP 141 PG 17 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA BL78N UT WOS:000076722300011 ER PT J AU Suzuki, K Proia, RL Suzuki, K AF Suzuki, K Proia, RL Suzuki, K TI Mouse models of human lysosomal diseases SO BRAIN PATHOLOGY LA English DT Article ID TAY-SACHS-DISEASE; HEMATOPOIETIC-CELL TRANSPLANTATION; SPHINGOMYELINASE-DEFICIENT MICE; BETA-GLUCURONIDASE DEFICIENCY; BONE-MARROW TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; NIEMANN-PICK DISEASE; TARGETED DISRUPTION; STORAGE DISEASE; METACHROMATIC LEUKODYSTROPHY AB Genetically authentic animal models of human lysosomal diseases occur spontaneously in many mammalian species, However, most are among larger domestic or farm animals with only two well-defined genetic lysosomal diseases known among rodents, This status changed dramatically in recent years with the advent of the combined homologous recombination and embryonic stem cell technology, which allows directed generation of mouse models that are genetically equivalent to human diseases. Almost all known human sphingolipidoses, two mucopolysaccharidoses and aspartylglycosaminuria have so far been duplicated in mice and more are expected in the near future, This technology also allows generation of mouse mutants that are not known or are highly unlikely to exist in humans, such as "double-knockouts." These animal models will play an important role in studies of the pathogenesis and treatment of these disorders, While the utility of these mouse models is obvious, species differences in brain development and metabolic pathways must be always remembered, if the ultimate goal of the study is application to human patients. C1 Univ N Carolina, Ctr Neurosci, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Suzuki, K (reprint author), Univ N Carolina, Ctr Neurosci, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. EM KIS@MED.UNC.Edu RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30-HD03110]; NINDS NIH HHS [R01-NS24453, R01-NS24289] NR 97 TC 35 Z9 36 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 1998 VL 8 IS 1 BP 195 EP 215 PG 21 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA YQ317 UT WOS:000071373200020 PM 9458176 ER PT J AU Fenton, H Finch, PW Rubin, JS Rosenberg, JM Taylor, WG Kuo-Leblanc, V Rodriguez-Wolf, M Baird, A Schipper, HM Stopa, EG AF Fenton, H Finch, PW Rubin, JS Rosenberg, JM Taylor, WG Kuo-Leblanc, V Rodriguez-Wolf, M Baird, A Schipper, HM Stopa, EG TI Hepatocyte growth factor (HGF/SF) in Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE hepatocyte growth factor; scatter factor; Alzheimer's disease (AD); cMet; growth factor ID TUMOR CYTOTOXIC FACTOR; C-MET; SCATTER FACTOR; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; RECEPTOR; EXPRESSION; PURIFICATION; TISSUES; PROTEIN AB Hepatocyte growth factor (HGF/SF), is a heparin-binding polypeptide which stimulates DNA synthesis in a variety of cell types and also promotes cell migration and morphogenesis. HGF/SF mRNA has been found in a variety of tissues, including brain. In a previous study, we showed that basic fibroblast growth factor (bFGF), another heparin-binding protein is increased in Alzheimer's disease (AD), and appears to be associated with the heparan-sulfate proteoglycans bound to B/A(4) amyloid (Biochem. Biophys. Res. Commun. 171 (1990) 690-696). In the present study, we examined the distribution of HGF/SF in 4% paraformaldehyde fixed samples of prefrontal cortex from control and Alzheimer patients, in order to assess the possibility that HGF/SF may be found in association with the pathologic changes which occur in Alzheimer's disease. A specific polyclonal antibody directed against HGF/SF revealed widespread HGF/SF-like immunoreactivity in both the cerebral cortex and white matter. Confocal microscopy confirmed that HGF/SF could be found in both GFAP positive astrocytes and LN3 positive microglia cells, as well as rare scattered cortical neurons. In the AD cases studied, the immunoreactivity was increased within both the astrocytes and microglial cells surrounding individual senile plaques. No staining was seen within the neurofibrillary tangles. Western blot analysis confirmed the normal molecular form of HGF/SF in Alzheimer's disease. Quantitative ELISA assay demonstrated a significant increase in HGF/SF in AD relative to age matched controls. These studies confirm the presence of HGF/SF immunoreactivity within neurons, astrocytes and microglial cells. They also indicate that HGF/SF may be increased within senile plaques as a function of the gliosis and microglial proliferation which occurs in association with these structures in Alzheimer's disease. (C) 1998 Elsevier Science B.V. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Dept Pathol,Neuropathol Div, Providence, RI 02903 USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. PRIZM Pharmaceut Corp, San Diego, CA USA. Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2T5, Canada. RP Stopa, EG (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Dept Pathol,Neuropathol Div, 593 Eddy St, Providence, RI 02903 USA. FU NIA NIH HHS [AG10682]; NIMH NIH HHS [MH/NS 31862] NR 23 TC 48 Z9 49 U1 0 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 JAN 1 PY 1998 VL 779 IS 1-2 BP 262 EP 270 DI 10.1016/S0006-8993(97)00958-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA YP875 UT WOS:000071324800029 PM 9473690 ER PT J AU Farber, JM AF Farber, JM TI Chemokines, lymphocytes, and HIV SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT International Meeting on Cytokines CY NOV 24-28, 1996 CL ANGRA REIS, BRAZIL DE cytokines; lymphoid cells; HIV-1; receptors ID PLATELET FACTOR-IV; GAMMA-INTERFERON; T-LYMPHOCYTES; CELL-LINE; RECEPTOR; INFECTION; CHEMOATTRACTANT; IDENTIFICATION; MURINE; SDF-1 AB Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-gamma and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3 alpha, and STRL22 has been renamed CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit. C1 NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, Bldg 10,Rm 11N-228 10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JAN PY 1998 VL 31 IS 1 BP 11 EP 17 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA YR478 UT WOS:000071499300002 PM 9686174 ER PT J AU Morawetz, RA Giese, NA Gabriele, L Rothman, P Horak, I Ozato, K Morse, HC AF Morawetz, RA Giese, NA Gabriele, L Rothman, P Horak, I Ozato, K Morse, HC TI Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT International Meeting on Cytokines CY NOV 24-28, 1996 CL ANGRA REIS, BRAZIL DE ICSBP; immunodeficiency; interferon; MAIDS ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MURINE LEUKEMIA-VIRUS; B-CELL LINEAGE; SYNDROME MAIDS; T-CELLS; AIDS VIRUS; ICSBP GENE; TH2 CELLS; MICE; RESISTANCE AB The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-gamma, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-gamma is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses, This immunodeficiency is associated with impaired production of IFN-gamma and IL-12, Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells, ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Res Inst Mol Pharmacol, Dept Mol Genet, Berlin, Germany. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 32 TC 6 Z9 6 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JAN PY 1998 VL 31 IS 1 BP 61 EP 67 DI 10.1590/S0100-879X1998000100008 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA YR478 UT WOS:000071499300008 PM 9686180 ER PT J AU Sher, A Gazzinelli, RT Jankovic, D Scharton-Kersten, T Yap, G Doherty, TM Wynn, T AF Sher, A Gazzinelli, RT Jankovic, D Scharton-Kersten, T Yap, G Doherty, TM Wynn, T TI Cytokines as determinants of disease and disease interactions SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT International Meeting on Cytokines CY NOV 24-28, 1996 CL ANGRA REIS, BRAZIL DE cytokines; disease; immunopathology; HIV-1; parasites; interleukin-10 ID SCHISTOSOMA-MANSONI; HELMINTH INFECTION; MICE; RESPONSES; IL-10 AB The immune response to pathogens results in both host resistance and Key words immunopathology. Cytokines and in particular those lymphokines Cytokines produced by Th1 and Th2 cells play a key role in determining the balance between these two immunologic outcomes. Recent data suggest that interleukin-10, a product of both Th2 cells and macrophages, protects the host against excessive immunopathology. The cytokine environment generated by different pathogens may also influence the course and outcome of infections with unrelated organisms. This relationship may be particularly important in the case of HIV-1 where prior Th1 or Th2 biases established by helminth or intracellular infections may influence either initial viral susceptibility or drive progression to AIDS through immune activation. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20854 USA. Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil. RP Sher, A (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20854 USA. NR 11 TC 7 Z9 8 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JAN PY 1998 VL 31 IS 1 BP 85 EP 87 DI 10.1590/S0100-879X1998000100011 PG 3 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA YR478 UT WOS:000071499300011 PM 9686183 ER PT J AU Cunha-Neto, E Rizzo, LV Albuquerque, F Abel, L Guilherme, L Bocchi, E Bacal, F Carrara, D Ianni, B Mady, C Kalil, J AF Cunha-Neto, E Rizzo, LV Albuquerque, F Abel, L Guilherme, L Bocchi, E Bacal, F Carrara, D Ianni, B Mady, C Kalil, J TI Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE Trypanosoma cruzi; Chagas' disease cardiomyopathy; immunology; cytokines; gamma-interferon ID TRYPANOSOMA-CRUZI INFECTION; NECROSIS-FACTOR-ALPHA; GAMMA-INTERFERON; IFN-GAMMA; MICE; INTERLEUKIN-10; SUSCEPTIBILITY; LYMPHOCYTES; MYOCARDITIS; MACROPHAGES AB The hallmark of chronic Chagas' disease cardiomyopathy (CCC) is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effecters of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996) Journal of Clinical Investigation, 98: 1709-1712). Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-gamma and TNF-alpha which may be linked to T. cruzi-induced IL-12 production. C1 Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao,Lab Imunol Transplantes, BR-05403000 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao,Div Clin, BR-05403000 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao,Div Cirurg, BR-05403000 Sao Paulo, Brazil. NEI, NIH, Bethesda, MD 20892 USA. RP Cunha-Neto, E (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao,Lab Imunol Transplantes, Av Eneas C Aguiar 500, BR-05403000 Sao Paulo, Brazil. RI Rizzo, Luiz Vicente/B-4458-2009; Cunha-Neto, Edecio/B-4157-2009; Guglielmi, Luiza/E-7676-2013; Ianni, Barbara/C-7689-2012; Mady, Charles/C-8870-2012; Bacal, Fernando/H-7952-2012; Abel, Lucia Cristina Jamli/P-8816-2014; OI Ianni, Barbara/0000-0002-1588-5492; Mady, Charles/0000-0002-8838-199X; Abel, Lucia Cristina Jamli/0000-0003-4915-4265; Cunha-Neto, Edecio/0000-0002-3699-3345 NR 30 TC 43 Z9 46 U1 1 U2 1 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD JAN PY 1998 VL 31 IS 1 BP 133 EP 137 DI 10.1590/S0100-879X1998000100018 PG 5 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA YR478 UT WOS:000071499300018 PM 9686190 ER PT J AU Steeg, PS Zhou, Q AF Steeg, PS Zhou, Q TI Cyclins and breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE cyclin D; cyclin E; DCIS; prevention; tumor progression ID CARCINOMA IN-SITU; CELL-CYCLE; GENE AMPLIFICATION; ESTROGEN-RECEPTOR; INHIBITS GROWTH; RETINOBLASTOMA PROTEIN; 9-CIS-RETINOIC ACID; DEPENDENT KINASES; REDUNDANT CYCLIN; PHASE-TRANSITION AB Cyclins are regulatory subunits for cyclin dependent kinases in the coordination of the cell cycle. Cyclins can also serve non-cell cycle functions, such as the transactivation of estrogen receptor by cyclin D. Evidence for the participation of the G(1) cyclins D and E in breast cancer is summarized, including transgenic and knockout mice, transfections, and expression patterns in cohort studies. Overexpression of cyclin D has been reported in ductal carcinoma in situ (DCIS), and similar overexpression of cyclin E is suggested. Strategies to reduce cyclin expression are discussed as potential prevention efforts. C1 NCI, Div Clin Sci, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. RP Zhou, Q (reprint author), NCI, Div Clin Sci, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. EM qz@helix.nih.gov NR 80 TC 92 Z9 95 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1998 VL 52 IS 1-3 BP 17 EP 28 DI 10.1023/A:1006102916060 PG 12 WC Oncology SC Oncology GA 169MR UT WOS:000078753100002 PM 10066069 ER PT J AU Bryant, J Fisher, B Gunduz, N Costantino, JP Emir, B AF Bryant, J Fisher, B Gunduz, N Costantino, JP Emir, B TI S-phase fraction combined with other patient and tumor characteristics for the prognosis of node-negative, estrogen-receptor-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE ER-positive breast cancer; heterogeneity of risk; prognostic models; S-phase fraction; smoothing splines ID TAMOXIFEN; SURVIVAL AB Women with estrogen-receptor (ER)-positive breast cancer and no axillary lymph-node involvement are considered to have excellent overall prognosis. However, this population is not homogeneous with regard to risk of recurrence; in fact, some of these patients have a prognosis no better than that of many women with ER-negative tumors or positive axillary nodes. Consequently, better tumor markers and better use of those currently available are needed to distinguish patients who would benefit from more aggressive therapy from those for whom such therapy is unnecessary. A well-defined cohort of over 4000 breast cancer patients from National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14 who had ER-positive tumors and no axillary lymph-node involvement was analyzed to ascertain the usefulness of tumor cell S-phase fraction for prognosis. The significance of clinical tumor size, patient age at surgery, ER and progesterone receptor (PgR) expression, and nuclear grade was also explored. Statistical methods based on smoothing splines were used to relate treatment failure and mortality rates to patient and tumor characteristics. Models for 5- and 10-year disease-free survival (DFS) and overall survival were developed and summarized. The attenuation of the prognostic importance of covariates over time was investigated. After other characteristics were accounted for, a strong association was found between S-phase fraction and DFS, as well as survival. Tumor size, patient age at surgery, and PgR status were also significantly associated with outcome. The diversity of risk in the B-14 population was more extreme than is generally recognized. The prognostic capabilities of S-phase, tumor size, and PgR status were sharply attenuated as the time from surgery increased. C1 Allegheny Univ Hlth Sci, Pittsburgh, PA 15212 USA. Univ Pittsburgh, NSABP, Pittsburgh, PA 15213 USA. RP Fisher, B (reprint author), Allegheny Univ Hlth Sci, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. EM bryant@ntsrvb.mckee.upmc.edu; bfisher1@aherf.edu FU NCI NIH HHS [NCI-U10-CA-37377, NCI-U10-CA-69651, NCI-U10-CA-12027] NR 17 TC 34 Z9 34 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1998 VL 51 IS 3 BP 239 EP 253 DI 10.1023/A:1006184428857 PG 15 WC Oncology SC Oncology GA 169AP UT WOS:000078725600005 PM 10068082 ER PT J AU Clifford, SC Hewson, K Walsh, S Brinke, A Green, PM Gianelli, F Pause, A Eng, C Maher, ER AF Clifford, SC Hewson, K Walsh, S Brinke, A Green, PM Gianelli, F Pause, A Eng, C Maher, ER TI Mutation analysis of von Hippel-Lindau (VHL) tumour suppressor-associated proteins, CUL-2 and VBP-1, in renal cell carcinoma (RCC) SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Birmingham, Dept Paediat & Child Hlth, Div Med & Mol Genet, Birmingham, W Midlands, England. United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Div Med & Mol Genet, London SE1 9RT, England. NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 1998 VL 78 SU 1 MA 36 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA ZV718 UT WOS:000074334100041 ER PT J AU Swan, N Mulligan, N Nikulasson, S Vortemeyer, AO Fogt, F AF Swan, N Mulligan, N Nikulasson, S Vortemeyer, AO Fogt, F TI Histogenesis of endothelial cells of cerebellar haemangioblastoma SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 Mallory Inst Pathol, Boston, MA 02118 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 PY 1998 VL 78 SU 1 MA P100 BP 49 EP 49 PG 1 WC Oncology SC Oncology GA ZV718 UT WOS:000074334100189 ER PT J AU Kim, WH Lee, BL Jun, SH Song, SY Kleinman, HK AF Kim, WH Lee, BL Jun, SH Song, SY Kleinman, HK TI Expression of 32/67-kDa laminin receptor in laminin adhesion-selected human colon cancer cell lines SO BRITISH JOURNAL OF CANCER LA English DT Article DE laminin; 32/67-kDa laminin receptor; laminin adhesion selection; colon cancer cell line; immunohistochemistry; affinity chromatography ID BINDING-PROTEIN; MELANOMA-CELLS; MESSENGER-RNA; PENTAPEPTIDE; PROGRESSION; MODULATION; PEPTIDE; YIGSR AB Laminin promotes the malignant phenotype, and the expression of certain laminin receptors is increased in malignancy. Previously, we demonstrated that a laminin-adhesive subclone of a human colon cancer cell line showed increased tumorigenicity in nude mice and increased affinity of the beta(1), integrin for laminin relative to the laminin-non-adhesive subclone. The total amount of either beta(1), integrin protein or mRNA did not increase. As levels of the 32/67-kDa laminin receptor (67LR) correlate with malignancy, we examined 67LR expression in the laminin adhesion-selected human colon cancer cells. The laminin-adhesive subclone, which was more tumorigenic in both heterotopic and orthotopic locations than in a laminin-non-adhesive subclone, showed cell-surface membrane staining of 67LR, whereas the laminin-non-adhesive subclone showed cytoplasmic staining of 67LR. No difference in either the amount of 67LR mRNA or the amount of protein was observed in the parental cells than in the laminin-adhesive and non-adhesive subclones. When assayed on a laminin affinity column, more 67LR molecules bound to the column with cell extracts from the laminin-adhesive subclone than was observed with the nonadhesive subclone. These findings suggest that the increased tumorigenicity of laminin adhesion-selected tumour cells might be due to an alteration in the distribution and/or adhesiveness of multiple receptors including 67LR and beta(1), integrin. C1 Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Dept Anat, Seoul 110799, South Korea. Seoul Natl Univ, Ctr Canc Res, Seoul 110799, South Korea. Kyoungpook Natl Univ, Coll Med, Dept Surg, Taegu 700422, South Korea. NIDR, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Kim, WH (reprint author), Seoul Natl Univ, Coll Med, Dept Pathol, 28 Yongon Dong, Seoul 110799, South Korea. RI Kim, Wooho/G-3703-2011; Seoul National University, Pathology/B-6702-2012; Lee, Byung Lan/J-5577-2012 NR 28 TC 22 Z9 24 U1 0 U2 2 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 JAN PY 1998 VL 77 IS 1 BP 15 EP 20 DI 10.1038/bjc.1998.3 PG 6 WC Oncology SC Oncology GA YR513 UT WOS:000071502800003 PM 9459140 ER PT J AU Chan, CC Li, Q AF Chan, CC Li, Q TI Immunopathology of uveitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEITIS; ENDOTOXIN-INDUCED UVEITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; RETINAL-PIGMENT EPITHELIUM; KOYANAGI-HARADA SYNDROME; T-HELPER LYMPHOCYTES; SYMPATHETIC OPHTHALMIA; S-ANTIGEN; MAST-CELLS; IMMUNE RESPONSIVENESS C1 NEI, Immunol Lab, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, Immunopathol Sect, NIH, Bldg 10,Room 10N103,10 Ctr Dr,MSC 1858, Bethesda, MD 20892 USA. NR 87 TC 15 Z9 18 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 1998 VL 82 IS 1 BP 91 EP 96 DI 10.1136/bjo.82.1.91 PG 6 WC Ophthalmology SC Ophthalmology GA YQ704 UT WOS:000071414900029 PM 9536890 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Ethanol-induced inhibition of a neuronal P2X purinoceptor by an allosteric mechanism SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE ion channel; ATP; alcohol; activation/deactivation kinetics; allosteric modulation ID RECEPTORS AB Ethanol inhibits a neuronal P2X purinoceptor by shifting the ATP concentration-response curve to the right in an apparently competitive manner. However, the underlying mechanism has not been determined. We investigated the effects of ethanol on the activation and deactivation time constants for ATP-activated current in bullfrog dorsal root ganglion neurones. Ethanol decreased the time constant of deactivation of ATP-gated ion channels without affecting the time constant of activation. The observations are not consistent with a competitive mechanism of inhibition by ethanol, but may be explained by an allosteric action of ethanol to decrease apparent agonist affinity. This represents a novel mechanism of action of ethanol on a neurotransmitter-gated ion channel. 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 9 TC 31 Z9 31 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 1998 VL 123 IS 1 BP 1 EP 3 DI 10.1038/sj.bjp.0701599 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YR967 UT WOS:000071550200001 PM 9484847 ER PT J AU Nithila, A Bourgeois, D Barmes, DE Murtomaa, H AF Nithila, A Bourgeois, D Barmes, DE Murtomaa, H TI WHO Global Oral Data Bank, 1986-96: an overview of oral health surveys at 12 years of age SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB The global oral health situation of 12-year-old children - decayed, missing, filled teeth (DMFT) index and the percentage of population affected - is described in this article using the latest representative studies for 80 countries included in the WHO Global Oral Data Bank (GODB) between 1986 and 1996. The quantity of information Varied considerably: 68% of developed market economies had at least one national data set, compared with 38% of developing countries and 36% of economies in transition. By WHO region, the proportions were as follows: Eastern Mediterranean, 55%; European, 50%; Western Pacific, 48%; African, 39%; South-East Asia, 30%; and the Americas, 26%. Globally, the weighted DMFT index for all data in the GODB is <3.0%, the WHO/Federation Dentaire Internationale goal for the year 2000. For the data reviewed in this article, achievement and nonachievement of this goal are discussed, as is the variation in DMFT means and proportions of children affected for various country groupings. There are difficulties in obtaining recent data for many countries, but the article emphasizes the need to maintain and develop the GODB to facilitate the compilation of valid, reliable and comparable data on oral health. C1 WHO, Oral Hlth Programme, Div Noncommunicable Dis, CH-1211 Geneva 27, Switzerland. NIDR, Bethesda, MD 20892 USA. Univ Helsinki, Dept Dent Publ Hlth, Helsinki, Finland. RP Nithila, A (reprint author), WHO, Oral Hlth Programme, Div Noncommunicable Dis, CH-1211 Geneva 27, Switzerland. NR 16 TC 21 Z9 23 U1 0 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1998 VL 76 IS 3 BP 237 EP 244 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 118BR UT WOS:000075818300002 PM 9744243 ER PT J AU Ellwein, LB Thulasiraj, RD Boulter, AR Dhittal, SP AF Ellwein, LB Thulasiraj, RD Boulter, AR Dhittal, SP TI Estimating costs of programme services and products using information provided in standard financial statements SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID CATARACT AB The financial viability of programme services and product offerings requires that revenue exceeds expenses. Revenue includes payments for services and products as well as donor cash and in-kind contributions. Expenses reflect consumption of purchased or contributed time and materials and utilization (depreciation) of physical plant facilities and equipment. Standard financial reports contain this revenue and expense information, complemented when necessary by valuation and accounting of in-kind contributions. Since financial statements are prepared using consistent and accepted accounting practices, year-to-year and organization-to-organization comparisons can be made. The use of such financial information is illustrated in this article by determining the unit cost of cataract surgery in two hospitals in Nepal. The proportion of unit cost attributed to personnel, medical supplies, administrative materials, and depreciation varied significantly by institution. These variations are accounted for by examining differences in operational structure and capacity utilization. C1 NEI, Bethesda, MD 20892 USA. Aravind Eye Hosp, Madurai, Tamil Nadu, India. Swiss Red Cross, Nepaigunj, Nepal. Lumbini Rana Ambika Eye Hosp, Bhairahawa, Nepal. RP Ellwein, LB (reprint author), NEI, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 5 TC 3 Z9 3 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1998 VL 76 IS 5 BP 459 EP 467 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 153FQ UT WOS:000077822500006 PM 9868836 ER PT J AU Parker, SL Davis, KJ Wingo, PA Ries, LAG Heath, CW AF Parker, SL Davis, KJ Wingo, PA Ries, LAG Heath, CW TI Cancer statistics by race and ethnicity SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article AB Key findings on cancer incidence and mortality are presented for five racial and ethnic groups in the United States-African Americans, American Indians, Asians and Pacific Islanders, Hispanics, and whites. Information on the prevalence of cancer risk factors and screening examinations among these racial and ethnic groups is also included. C1 Amer Canc Soc, Dept Epidemiol & Surveillance, Surveillance Res Program, Atlanta, GA 30329 USA. NCI, Div Canc Prevent & Control, Canc Control Res Program, Bethesda, MD 20892 USA. RP Parker, SL (reprint author), Amer Canc Soc, Dept Epidemiol & Surveillance, Surveillance Res Program, Atlanta, GA 30329 USA. NR 15 TC 185 Z9 187 U1 0 U2 3 PU AMER CANCER SOC, INC PI ATLANTA PA 1599 CLIFTON RD, NE, ATLANTA, GA 30329 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 1998 VL 48 IS 1 BP 31 EP + DI 10.3322/canjclin.48.1.31 PG 19 WC Oncology SC Oncology GA YR587 UT WOS:000071510200003 PM 9449932 ER PT J AU Freeman, HP AF Freeman, HP TI The meaning of race in science - Considerations for cancer research - Concerns of special populations in the National Cancer Program SO CANCER LA English DT Editorial Material DE President's Cancer Panel; ethnicity; race; science AB Popular conceptualizations of race date back several centuries and, in particular, are rooted in 19th and early 20th century scientific thought. Such racial categories are based on externally visible traits, primarily skin color and facial features, but also on the shape and size of the head and body, The presumption was that immutable visible traits produced the measure of all other traits in an individual or a population. This presumption persists although scientists now estimate that all externally visible traits represent only 0.01% expression of the 100,000 genes that each individual has. In the past, some scientists used observations of racial differences to support racist doctrines such as the superiority of one race over another. An important example of this is illustrated by the studies of Samuel George Morton in the mid-19th century. One of the most respected scientists of his time, Morton published three major works on the sizes of human skulls. Morton's craniometry concluded that blacks and Native Americans had smaller brains and, therefore, less intelligence when compared with whites, an argument supporting the concept of polygenism that held that human races were separate biologic species. C1 NCI, Presidents Canc Panel, Bethesda, MD 20892 USA. RP Freeman, HP (reprint author), NCI, Presidents Canc Panel, 31 Ctr Dr MSC 2473,Bldg 31,Room 4A48, Bethesda, MD 20892 USA. NR 0 TC 65 Z9 68 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1998 VL 82 IS 1 BP 219 EP 225 DI 10.1002/(SICI)1097-0142(19980101)82:1<219::AID-CNCR27>3.0.CO;2-4 PG 7 WC Oncology SC Oncology GA YQ535 UT WOS:000071397500026 PM 9428500 ER PT B AU Greenwald, P AF Greenwald, P BE Prasad, KN Cole, WC TI The cancer prevention program at the National Cancer Institute SO CANCER AND NUTRITION LA English DT Proceedings Paper CT Conference on Vitamins and Nutrients in Cancer Prevention and Treatment CY JUL 16-21, 1997 CL IRVINE, CA SP Canc Treatment Ctr Fdn, NCI, Henkel Corp, Abbott Labs, Tisheon Corp, Hoffman La Roche, BASF, Samuel Freeman Charitable Trust, Mead Johnson Nutr Grp AB Two major complementary programs at the National Cancer Institute (NCI) give high priority to cancer prevention. The diet and nutrition program conducts research in prevention-related epidemiology, nutritional and molecular regulation, and dietary intervention trials to identify and evaluate cancer-preventive dietary patterns. The chemoprevention program identifies and assesses specific chemical substances, many naturally occurring in foods, with potential to prevent cancer initiation and to either slow or reverse the progression of premalignant lesions to invasive cancer. Evidence suggests that dietary fat, excessive calories, obesity, and alcohol increase cancer risk, whereas vegetables, fruits, whole grains, dietary fiber, and perhaps selected micronutrients are protective. Not all data are consistent, likely a result of methodological differences, interactions of dietary constituents, and individual genetic susceptibilities. Dietary epidemiology has helped to identify naturally occurring chemopreventive agents that may influence carcinogenesis at various sites. The development of chemopreventive agents follows a well-defined strategy that includes preclinical and early phase clinical testing, short-term clinical studies, and large-scale randomized, controlled intervention trials. Efforts to validate molecular biomarkers for identification of high-risk populations, early detection of premalignancies, and determination of the efficacy of dietary and chemopreventive interventions are a crucial part of cancer prevention research. The NCI considers large-scale intervention trials to be the best means available to test whether dietary and chemopreventive interventions actually do reduce cancer risk. Current trials include dietary interventions (e.g., low fat and/or high fiber or high vegetables/fruits) targeting breast and colorectal cancers, and chemoprevention trials using micronutrients (e.g., vitamin D, calcium, vitamin E) that are aimed at lung and colorectal cancers. C1 NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent & Control, NIH, Bldg 31 Room 10A52, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS BN 90-5199-377-3 PY 1998 BP 3 EP 19 PG 17 WC Oncology; Medicine, General & Internal; Nutrition & Dietetics SC Oncology; General & Internal Medicine; Nutrition & Dietetics GA BL27B UT WOS:000074946900001 ER PT J AU Hartman, TJ Albanes, D Rautalahti, M Tangrea, JA Virtamo, J Stolzenberg, R Taylor, PR AF Hartman, TJ Albanes, D Rautalahti, M Tangrea, JA Virtamo, J Stolzenberg, R Taylor, PR TI Physical activity and prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE exercise; Finland; men; physical activity; prostate cancer ID RISK; EXERCISE; HORMONE; MEN; TESTOSTERONE; ESTRADIOL; GROWTH; SITES AB The association between physical activity and prostate cancer was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (n = 29,133). During up to nine years of follow-up, 317 men developed incident prostate cancer. The relationship between occupational, leisure, and combined activity and prostate cancer was assessed in multivariate Cox regression models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence. Compared with sedentary workers, relative risks (RR) and 95 percent confidence intervals (CI) for occupational walkers, walker/lifters, and heavy laborers were 0.6 (CI = 0.4-1.0), 0.8 (CI = 0.5-1.3), and 1.2 (CI = 0.7-2.0), respectively. Among working men, leisure activity (active cf sedentary) was associated inversely with risk (RR = 0.7, CI = 0.5-0.9). This inverse association for leisure activity was observed, with the exception of heavy laborers, for all occupational activity levels, and was strongest among walkers compared with men sedentary at work and leisure, and to a lesser degree among walker/lifters. These results are consistent with a protective effect of physical activity on prostate cancer. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. RP Hartman, TJ (reprint author), NCI, Div Clin Sci, Execut Plaza N,Suite 211,6130 Execut Blvd MSC 732, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN 45165] NR 49 TC 51 Z9 51 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1998 VL 9 IS 1 BP 11 EP 18 DI 10.1023/A:1008889001519 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YV685 UT WOS:000071852500003 PM 9486459 ER PT J AU Doody, MM Mandel, JS Lubin, JH Boice, JD AF Doody, MM Mandel, JS Lubin, JH Boice, JD TI Mortality among United States radiologic technologists, 1926-90 SO CANCER CAUSES & CONTROL LA English DT Article DE mortality; neoplasms (radiation-induced); occupational diseases; radiologic technicians; United States ID ATOMIC-BOMB SURVIVORS; BREAST-CANCER; LUNG-CANCER; TUBERCULOSIS PATIENTS; IONIZING-RADIATION; WORKERS; COHORT; MASSACHUSETTS; FLUOROSCOPY; EXPOSURE AB The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths), Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Doody, MM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza N,Room 408, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-21015, N01-CP-61006, N01-CP-81058] NR 27 TC 72 Z9 74 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1998 VL 9 IS 1 BP 67 EP 75 DI 10.1023/A:1008801404245 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YV685 UT WOS:000071852500009 PM 9486465 ER PT J AU Dorgan, JF Sowell, A Swanson, CA Potischman, N Miller, R Schussler, N Stephenson, HE AF Dorgan, JF Sowell, A Swanson, CA Potischman, N Miller, R Schussler, N Stephenson, HE TI Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE alpha-tocopherol; breast neoplasms; carotenoids; nutrition; retinol; selenium; women; United States ID VITAMIN-E LEVELS; BETA-CAROTENE; CIGARETTE-SMOKING; SUBSEQUENT RISK; DIETARY FACTORS; NEW-YORK; ALCOHOL-CONSUMPTION; SOUTHERN FRANCE; PLASMA RETINOL; FINNISH MEN AB To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States), Women free of cancer donated blood to this bank in 1977-87, During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed, For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women, Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident, A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Environm Hlth Lab Sci, Natl Ctr Environm Hlth, Atlanta, GA USA. Ellis Fischel Canc Ctr, Columbia, MO USA. Informat Management Serv Inc, Silver Spring, MD USA. Univ Missouri, Hlth Sci Ctr, Columbia, MO USA. RP Dorgan, JF (reprint author), NCI, Div Epidemiol & Genet, Execut Plaza N,Room 443,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 67 TC 127 Z9 132 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1998 VL 9 IS 1 BP 89 EP 97 DI 10.1023/A:1008857521992 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YV685 UT WOS:000071852500012 PM 9486468 ER PT J AU Inskip, PD Mellemkjaer, L Gridley, G Olsen, JH AF Inskip, PD Mellemkjaer, L Gridley, G Olsen, JH TI Incidence of intracranial tumors following hospitalization for head injuries (Denmark) SO CANCER CAUSES & CONTROL LA English DT Article DE brain neoplasms; Denmark; glioma; head trauma; hemangioblastoma; meningioma ID LOS-ANGELES COUNTY; EXPLORATORY CASE-CONTROL; CENTRAL NERVOUS-SYSTEM; BRAIN-TUMORS; RISK-FACTORS; LINDAU DISEASE; TRAUMA; CANCER; MENINGIOMAS; CHILDREN AB The incidence of brain and other intracranial tumors following head trauma was evaluated in a cohort of 228,055 Danish residents hospitalized because of concussion, fractured skull, or other head injury between 1977 and 1992 and followed for an average of eight years (maximum, 17 years). Traffic accidents, falls, and sports-related incidents were the usual causes of the injury. Malignant and benign neoplasms were identified by linking the study roster with records of the Danish Cancer Registry for the years 1977 to 1993. This approach precludes differential reporting of injuries by study participants as an explanation for any associations seen. Intracranial tumors of the nervous system occurred more often than expected based on incidence rates for the Danish population; however, most of the excess occurred during the first year after the injury and likely was due to the detection of tumors that were present before the injury occurred. Excluding the first year of follow-up, the standardized incidence ratio (SIR) was 1.15 (95 percent confidence interval [CI] = 0.99-1.32). The same general temporal pattern was seen for the major subtypes of brain tumor as for all types combined. SIRs after the first year were 1.0 for glioma (CI = 0.8-1.2), 1.2 for meningioma (CI = 0.8-1.7), and 0.8 for neurilemmoma (CI = 0.4-1.7). However, hemangioblastoma and hemangioma were more frequent than expected, based on 15 cases (SIR = 2.6, CI = 1.4-4.2). Results indicate that head trauma causes, at most, a small increase in the overall risk of brain tumors during the ensuing 15 years; however, a possible association with intracranial vascular tumors warrants further evaluation. C1 Texas A&M Univ, Coll Vet Med, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Danish Canc Soc, Div Canc Epidemiol, Copenhagen, Denmark. RP Inskip, PD (reprint author), Texas A&M Univ, Coll Vet Med, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. NR 37 TC 59 Z9 61 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1998 VL 9 IS 1 BP 109 EP 116 DI 10.1023/A:1008861722901 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YV685 UT WOS:000071852500014 PM 9486470 ER PT J AU Freedman, AN Michalek, AM Weiss, HA Zhang, ZF Marshall, JR Mettlin, CJ Asirwatham, JE Petrelli, NJ Caporaso, NE AF Freedman, AN Michalek, AM Weiss, HA Zhang, ZF Marshall, JR Mettlin, CJ Asirwatham, JE Petrelli, NJ Caporaso, NE TI Aspirin use and p53 expression in colorectal cancer SO CANCER DETECTION AND PREVENTION LA English DT Article DE aspirin; colorectal; epidemiology; p53 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER; LARGE-BOWEL; SULINDAC SULFIDE; REDUCED RISK; OVEREXPRESSION; ADENOMAS; ADENOCARCINOMA; SMOKING; TUMORS AB p53 protein overexpression indicates loss of tumor suppressor activity and is the most common genetic alteration in colorectal neoplasms. Epidemiologic and experimental studies suggest that regular use of aspirin may reduce colorectal cancer risk. We set out to determine whether p53 overexpression of the colorectum was associated with a patient's history of aspirin use. Self-administered questionnaires, including information on aspirin use, were obtained from 163 patients with nonfamilial colorectal cancer and from 326 healthy controls. Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse association was observed between use of aspirin and colorectal cancer. Compared with that for nonusers, the odds ratio (OR) for individuals who took aspirin at least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The odds ratio for those individuals who used aspirin for less than 5 years was 0.54 (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for 5 years or more, when compared with nonusers. An inverse association of regular aspirin use (two times per week or more) was found both for cases with p53 overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53 overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was Little evidence of a difference in the effect of aspirin use on cancer risk between cases with and without p53 overexpression, even after adjustment for potential confounders. C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Freedman, AN (reprint author), NCI, Appl Res Branch, EPN, Rm 313,6130 Execut Blvd,MSC-7344, Bethesda, MD 20892 USA. FU NCI NIH HHS [R25 CA18201-19] NR 34 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1998 VL 22 IS 3 BP 213 EP 218 PG 6 WC Oncology SC Oncology GA ZM483 UT WOS:000073544700004 PM 9618042 ER PT J AU Roberts, JD Klein, JLD Palmantier, R Dhume, ST George, MD Olden, K AF Roberts, JD Klein, JLD Palmantier, R Dhume, ST George, MD Olden, K TI The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer SO CANCER DETECTION AND PREVENTION LA English DT Article DE arachidonic acid; cell adhesion; hematopoietic progenitor cells; metastasis; protein kinase C; swainsonine ID KINASE C-ALPHA; FOCAL ADHESION FORMATION; MURINE MELANOMA-CELLS; HAMSTER-KIDNEY CELLS; NUDE-MICE; TUMOR-CELLS; TYROSINE PHOSPHORYLATION; LINKED OLIGOSACCHARIDES; EXTRACELLULAR-MATRIX; LINOLEIC-ACID AB Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. We are currently characterizing the ability of swainsonine to modify cell growth in human and murine bone marrow progenitor cells. Furthermore, we are examining crucial steps in metastasis that depend upon cell surface molecules that play a role in cell-matrix interactions. Our work shows that tumor cell adhesion to collagen IV in vitro is rapidly stimulated by cis-polyunsaturated fatty acids and is dependent on protein kinase C activity. We are investigating the hypothesis that integrins are critical components of this adhesion and are examining potential signal transduction pathways that lead to the modulation of cell adhesion. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Roberts, JD (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,Mail Drop C2-14, Res Triangle Pk, NC 27709 USA. NR 71 TC 22 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1998 VL 22 IS 5 BP 455 EP 462 DI 10.1046/j.1525-1500.1998.00054.x PG 8 WC Oncology SC Oncology GA 112ER UT WOS:000075481600010 PM 9727627 ER PT J AU Lawrence, JA Merino, MJ Simpson, JF Manrow, RE Page, DL Steeg, PS AF Lawrence, JA Merino, MJ Simpson, JF Manrow, RE Page, DL Steeg, PS TI A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-ERBB-2 ONCOGENE EXPRESSION; P53 PROTEIN EXPRESSION; CYCLIN D1; THYROID-HORMONE; IN-SITU; CELL-LINES; ESTROGEN-RECEPTOR; GENE AMPLIFICATION; SIGNALING PATHWAYS; NUCLEAR RECEPTOR AB The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis, We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer, The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section, Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma iii situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk, In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008), Limited irt situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated, Immunohistochemistry performed on 52 DCIS specimens for alpha,beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form, The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed. C1 NCI, Chemprevent Branch, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Womens Canc Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. RP Lawrence, JA (reprint author), NCI, Chemprevent Branch, Div Canc Prevent, NIH, EPN 201, Bethesda, MD 20892 USA. EM julial@helix.nih.gov NR 74 TC 33 Z9 33 U1 0 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 JAN PY 1998 VL 7 IS 1 BP 29 EP 35 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800006 PM 9456240 ER PT J AU Hu, N Taylor, PR Rao, JY Hemstreet, GP Liu, SF Zou, XN Mark, SD Dawsey, SM AF Hu, N Taylor, PR Rao, JY Hemstreet, GP Liu, SF Zou, XN Mark, SD Dawsey, SM TI Quantitative fluorescence image analysis of DNA content and nuclear morphology on esophageal balloon cytology smears and subsequent development of esophageal and gastric cardia cancer in Linxian, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK; POPULATION; CELLS AB The highest incidences of esophageal and gastric cardia cancer in the world occur in northern China, Chinese scientists have developed esophageal balloon cytology screening to detect these cancers, but traditional cytology is sometimes inadequate to find some early, curable lesions, Several studies suggest that quantitative fluorescence image analysis (QFIA) of DNA ploidy and nuclear morphology may be able to improve upon traditional cytology results, In October 1987, esophageal balloon cytology was performed on 1331 adults in Linxian, China, and all samples were evaluated both by traditional cytology and QFIA, From 1987 to May 1991, 62 new squamous esophageal cancers and 44 new adenocarcinomas of the cardia were identified in this cohort, Proportional hazards models were used to evaluate the relationship of cytological diagnoses and six QFIA variables to subsequent cancer risk, These models showed significant trends for increasing esophageal cancer risk, with increasing values in five of the QFIA variables and with increasing severity of the traditional cytological diagnoses, A comparison of models with only cytology variables versus models with both cytology and QFIA variables indicated that the QFIA provided an important additional predictive value, Persons with both cytological dysplasia and high cellular DNA were 8 times more likely to develop esophageal cancer than were individuals with neither of these conditions, For cardia cancer, associations between QFIA variables or cytological diagnoses and later cancer were more limited, This study suggests that the QFIA variables evaluated here are independent predictors of squamous esophageal cancer and that combining QFIA with traditional cytology can improve prediction of esophageal cancer risk. C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Univ Oklahoma, Oklahoma City, OK 73190 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Hu, N (reprint author), NCI, Canc Prevent Studies Branch, Execut Plaza N,Room 211,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 3 Z9 3 U1 0 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 JAN PY 1998 VL 7 IS 1 BP 59 EP 64 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800010 PM 9456244 ER PT J AU Kelloff, GJ Lubet, RA Lieberman, R Eisenhauer, K Steele, VE Crowell, JA Hawk, ET Boone, CW Sigman, CC AF Kelloff, GJ Lubet, RA Lieberman, R Eisenhauer, K Steele, VE Crowell, JA Hawk, ET Boone, CW Sigman, CC TI Aromatase inhibitors as potential cancer chemopreventives SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID ADVANCED BREAST-CANCER; BENIGN PROSTATIC HYPERPLASIA; INDUCED MAMMARY-TUMORS; METHYL-N-NITROSOUREA; HEALTHY POSTMENOPAUSAL WOMEN; ESTROGEN BIOSYNTHESIS; PHASE-I; PERIPHERAL AROMATIZATION; DORSOLATERAL PROSTATE; FADROZOLE HYDROCHLORIDE AB Epidemiological and experimental evidence strongly supports a role for estrogens in the development and growth of breast tumors. A role for estrogen in prostate neoplasia has also been postulated. Therefore, one chemopreventive strategy for breast and prostate cancers is to decrease estrogen production. This can be accomplished by inhibiting aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis. The use of aromatase inhibitors is of clinical interest for cancer therapy, and selective, potent aromatase inhibitors have been developed. Several of these agents have demonstrated chemopreventive efficacy in animal models. The rationale for the use of aromatase inhibitors as chemopreventives and identification of inhibitors to serve as potential chemopreventive agents are the subjects of this review. After background information regarding aromatase is presented, the data for each inhibitor are summarized separately. The discussion focuses on those inhibitors that are clinically available or in clinical trials, including: aminoglutethimide (Cytadren), rogletimide, fadrozole hydrochloride, liarozole hydrochloride, anastrozole (Arimidex), letrozole, vorozole, formestane, exemestane, and atamestane. On the basis of results from preclinical studies, aromatase inhibitors may be promising agents for clinical trials in populations at high risk for developing estrogen-dependent cancers. Total suppression of aromatase may have adverse effects, as is evident in postmenopausal women (increased osteoporosis, cardiovascular disease, and urogenital atrophy). However, on the basis of preclinical studies of chemopreventive efficacy and chemotherapeutic applications of aromatase inhibitors showing dose-response efficacy, it may be possible to obtain chemopreventive effects without total suppression of aromatase and circulating estrogen levels. Suppressing local estrogen production may be an alternative strategy, as suggested by the discovery of a unique transcriptional promoter of aromatase gene expression, I.4, in breast adipose tissue. The development of drugs that target this promoter region may be possible. C1 NCI, Chemoprevent Branch, Div Canc Prevent & Control, Rockville, MD 20852 USA. CCS Associates, Mt View, CA 94043 USA. RP Kelloff, GJ (reprint author), NCI, Chemoprevent Branch, Div Canc Prevent & Control, Execut Plaza N,Suite 201,6130 Execut Blvd, Rockville, MD 20852 USA. NR 150 TC 54 Z9 54 U1 3 U2 7 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 JAN PY 1998 VL 7 IS 1 BP 65 EP 78 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800011 PM 9456245 ER PT J AU Hsing, AW Devesa, SS Jin, F Gao, YT AF Hsing, AW Devesa, SS Jin, F Gao, YT TI Rising incidence of prostate cancer in Shanghai, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai 200032, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPN-443,6130 Execut Blvd, Bethesda, MD 20892 USA. EM hsinga@epndce.nci.nih.gov NR 7 TC 30 Z9 32 U1 0 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 JAN PY 1998 VL 7 IS 1 BP 83 EP 84 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800013 PM 9456247 ER PT J AU Reed, E AF Reed, E TI Should cost be considered in the overall evaluation of phase II clinical trials of new antineoplastic therapies? A response SO CANCER INVESTIGATION LA English DT Article DE ovarian cancer; paclitaxel; G-CSF; dose intensity ID COLONY-STIMULATING FACTOR; DOSE-INTENSE TAXOL; GYNECOLOGIC-ONCOLOGY-GROUP; CELL LUNG-CANCER; OVARIAN-CANCER; RECURRENT ADENOCARCINOMA; PACLITAXEL; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; CARCINOMA C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Branch, Div Clin Sci, Bldg 10,Room 12C103, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1998 VL 16 IS 2 BP 135 EP 139 DI 10.3109/07357909809039766 PG 5 WC Oncology SC Oncology GA ZA375 UT WOS:000072357200008 PM 9512678 ER PT J AU Gause, BL Sharfman, WH Janik, JE Curti, BD Steis, RG Urba, WJ Smith, JW Alvord, WG Longo, SL AF Gause, BL Sharfman, WH Janik, JE Curti, BD Steis, RG Urba, WJ Smith, JW Alvord, WG Longo, SL TI A phase II study of carboplatin, cisplatin, interferon-alpha, and tamoxifen for patients with metastatic melanoma SO CANCER INVESTIGATION LA English DT Article ID HIGH-DOSE CISPLATIN; COMBINATION CHEMOTHERAPY; CLONOGENIC-ASSAY; CYTO-TOXICITY; DACARBAZINE; TRIAL; AUGMENTATION; XENOGRAFTS; AGENTS; TUMORS AB The purpose of this trial was to determine the toxicity and antineoplastic activity of cisplatin, carboplatin, tamoxifen, and interferon-alpha (IFN-alpha) in patients with advanced melanoma. Eleven patients with metastatic melanoma,were enrolled. The patients received carboplatin 400 mg/m(2) IV on day 0; cisplatin 25 mg/m(2) IV on clays 7, 14 and 21; tamoxifen 20 mg p.o. b.i.d. on days 0-27; and interferon-alpha 5 million units/m(2) subcutaneously 3 times per week. Cycles were repeated every 28 days. Patients were assessed for tumor response at the end of 2 cycles. Toxicity was severe, with 14 of 24 cycles given requiring some form of dose reduction. Carboplatin dose reductions were related to bone-marrow toxicity whereas IFN-alpha caused fatigue, arthralgias, myalgias, and fever. The overall response rate was 18% (2 partial responses [PRs]). The combination of cisplatin, carboplatin, tamoxifen, and IFN-alpha is active in advanced melanoma; however the toxicity is unacceptable. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick Clin Res Branch, Frederick, MD 21701 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA. RP Gause, BL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick Clin Res Branch, 501 W 7th St, Frederick, MD 21701 USA. NR 28 TC 9 Z9 9 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1998 VL 16 IS 6 BP 374 EP 380 DI 10.3109/07357909809115776 PG 7 WC Oncology SC Oncology GA 102KY UT WOS:000074924500003 PM 9679527 ER PT J AU Alexander, HR Bartlett, DL Libutti, SK AF Alexander, HR Bartlett, DL Libutti, SK TI Isolated hepatic perfusion: A potentially effective treatment for patients with metastatic or primary cancers confined to the liver SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article ID TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; PROSPECTIVE RANDOMIZED TRIAL; COLORECTAL-CARCINOMA; UVEAL MELANOMA; HEPATOCELLULAR-CARCINOMA; ARTERIAL FLOXURIDINE; INTERFERON-GAMMA; PHASE-I; CHEMOTHERAPY C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B17, Bethesda, MD 20892 USA. NR 55 TC 27 Z9 27 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 JAN-FEB PY 1998 VL 4 IS 1 BP 2 EP 11 PG 10 WC Oncology SC Oncology GA YU910 UT WOS:000071768700001 PM 9467038 ER PT J AU Harris, KA AF Harris, KA TI The informational needs of patients with cancer and their families SO CANCER PRACTICE LA English DT Article DE attitude to health; communication; decision making; neoplasms; patient education; patient information ID BREAST-CANCER; COMMUNICATION; CARE; WOMEN AB PURPOSE: Seven years ago, the National Cancer Institute compiled a. review of the literature published from 1979 to 1990 on information, education, and communication needs of patients with cancer and their families. Because of its potential value to health professionals and to the community, an updated report of relevant literature is presented in this article. The report provides analysis to assist health professionals in tailoring the quantity, variety, and timing of information they present to the patient with cancer and his or her family. OVERVIEW: This review incorporates a sample of 66 articles published from 1990 to 1997. Of these, 44 articles address the information, education, and communication needs of patients with cancer and their families. The discussion focuses on how health professionals can maximize patient comprehension and retention of information, encourage patient participation in health decision making, and foster dialogue with patients and families. CLINICAL IMPLICATIONS: Steps should be taken within healthcare organizations to ensure that ongoing informational needs assessment and education are a routine put of comprehensive cancer patient care. This analysis points to the importance of tailoring information to meet patients' educational background, cultural orientation, and general level of comprehension. Healthcare providers must not only consider the degree to which a patient with cancer desires information, but also bow active a role he or she wishes to take in making treatment decisions. In addition, health professionals should be aware that the informational needs of patients and family members change throughout the course of care and therefore should be reassessed periodically. C1 NCI, Patient Educ Branch, Off Canc Commun, NIH, Bethesda, MD 20892 USA. RP Harris, KA (reprint author), NCI, Patient Educ Branch, Off Canc Commun, NIH, 9000 Rockville Pike,Bldg 31,Rm 10A10, Bethesda, MD 20892 USA. NR 44 TC 112 Z9 114 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD JAN-FEB PY 1998 VL 6 IS 1 BP 39 EP 46 DI 10.1046/j.1523-5394.1998.1998006039.x PG 8 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA ZG094 UT WOS:000072965000006 PM 9460325 ER PT J AU Tsao, H Benoit, E Sober, AJ Thiele, C Haluska, FG AF Tsao, H Benoit, E Sober, AJ Thiele, C Haluska, FG TI Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; FAMILIAL MELANOMA; CELL-LINES; HOMOZYGOUS DELETIONS; CDK4; P16; INHIBITOR; P16(INK4); CANCER; GLIOMA AB Mutations in genes that lie in the retinoblastoma pathway have been implicated in the pathogenesis of many tumor types, Two critical components that determine progression from G(1) to S include p16/CDKN2A and CDK4 Alterations in p16/CDKN2A have been well documented in multiple cancers, including melanoma, However, changes in CDK4 are apparently more rare. Only two alterations, both at codon 24, have been identified in CDK4: an activating arginine-to-cysteine transition and a germ-line arginine-to-histidine substitution in one French kindred, In a survey of 20 neuroblastomas, 17 uncultured metastatic melanomas, 33 uncultured primary uveal melanomas, 8 colon cancer cell lines, and 20 primary colon cancer samples, we found no evidence of mutations in exon 2 of CDK4. From our cell lines derived from metastatic melanomas, we detected two alterations in the functionally critical exon 2 of CDK4: a lysine-to-glutamine transition at codon 22 and the arginine-to-histidine mutation at codon 24. These findings document several novel changes in the p16-binding region of CDK4. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Dana Farber Canc Inst, Partner Canc Care, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Jackson 1021,Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [5T32AR07098-23] NR 37 TC 66 Z9 67 U1 1 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 JAN 1 PY 1998 VL 58 IS 1 BP 109 EP 113 PG 5 WC Oncology SC Oncology GA YN977 UT WOS:000071229000021 PM 9426066 ER PT J AU Santoni-Rugiu, E Jensen, MR Thorgeirsson, SS AF Santoni-Rugiu, E Jensen, MR Thorgeirsson, SS TI Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor alpha SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; S-PHASE ENTRY; HUMAN HEPATOCELLULAR-CARCINOMA; UBIQUITIN-PROTEASOME PATHWAY; TRANSCRIPTION FACTOR E2F-1; TUMOR-SUPPRESSOR PROTEIN; TRANSGENIC MOUSE MODEL; RETINOBLASTOMA PROTEIN; DEREGULATED EXPRESSION; NEOPLASTIC DEVELOPMENT AB The oncogene c-myc and transforming growth factor (TGF) alpha are frequently coexpressed in human cancers, suggesting that their interaction may be a critical step in malignant growth. Consistent with this idea, we recently demonstrated in a transgenic mouse model that TGF-alpha dramatically enhances c-myc-induced hepatocarcinogenesis. To elucidate this synergistic effect, we have now investigated regulation of cell cycle and apoptosis during neoplastic development in the liver of c-myc and c-myc/TGF alpha transgenic mice. Both lines displayed dramatic increases of mitotic and apoptotic rates before the onset of hepatocellular carcinoma (HCC), but only c-myc/TGF-alpha livers shelved significant levels of net proliferation (mitosis minus apoptosis). Subsequently, mitosis declined in peritumorous tissues, concomitant with the previously reported induction of TGF-beta 1, whereas c-myc and c-myc/TGF alpha HCCs maintained mitotic hyperactivity. The c-myc/TGF-alpha HCCs were also characterized by a particularly strong expression of TGF-alpha and very low apoptotic index in contrast to high levels of apoptosis in peritumorous tissues and c-myc HCCs. The differential levels of cell proliferation in noncancerous and cancerous tissues correlated with a stronger induction of cyclin D1 mRNA and protein in c-myc/TGF-alpha and c-myc HCCs associated with intense pRb hyperphosphorylation. Severe deregulation of G(1)-S transition was also indicated by the dramatic up-regulation, particularly in the HCCs, of pRb-free E2F1-DP1 and E2F2-DP1 transcription factor heterodimers, as assessed by immunoprecipitation and immunohistochemistry. The existence of increased E2F activity during hepatocarcinogenesis was further indicated by the transcriptional induction of putative E2F target genes involved in cell cycle progression, such as endogenous c-myc, cyclin A, Cdc2, and E2F itself. Cdc2 overexpression and the elevated mitotic indices in the HCCs correlated also with induction of cyclin B steady-state levels. The data suggest that coexpression of c-myc and TGF-alpha leads to a selective growth advantage for hepatic (pre)neoplastic cells by disrupting the pRb/E2F pathway and hy TGF-alpha-mediated reduction of apoptosis. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bldg 37,Room 3C28,37 Convent Dr,MSC4255, Bethesda, MD 20892 USA. RI Jensen, Michael/E-9677-2011 NR 84 TC 109 Z9 113 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 JAN 1 PY 1998 VL 58 IS 1 BP 123 EP 134 PG 12 WC Oncology SC Oncology GA YN977 UT WOS:000071229000023 PM 9426068 ER PT J AU Boone, CW Kelloff, GJ AF Boone, CW Kelloff, GJ TI Endpoint markers for clinical trials of chemopreventive agents derived from the properties of epithelial precancer (intraepithelial neoplasia) measured by computer-assisted image analysis SO CANCER SURVEYS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GENETIC ALTERATIONS; BARRETTS-ESOPHAGUS; ACTINIC KERATOSIS; TUMOR PROGRESSION; FLOW-CYTOMETRY; DNA-ANALYSIS; LESIONS; CANCER; DYSPLASIA C1 NCI, Chemoprevent Branch, Div Canc Prevent, Rockville, MD 20892 USA. RP Boone, CW (reprint author), NCI, Chemoprevent Branch, Div Canc Prevent, Rockville, MD 20892 USA. NR 40 TC 6 Z9 6 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1998 VL 32 BP 133 EP 147 PG 15 WC Oncology SC Oncology GA 119LK UT WOS:000075897500007 PM 10489626 ER PT J AU Smith, MR Court, DW Kim, HK Park, JB Rhee, SG Rhim, JS Kung, HF AF Smith, MR Court, DW Kim, HK Park, JB Rhee, SG Rhim, JS Kung, HF TI Overexpression of phosphoinositide-specific phospholipase C gamma in NIH 3T3 cells promotes transformation and tumorigenicity SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE; DNA-SYNTHESIS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; MITOGENIC SIGNAL; FISSION YEAST; CYCLE CONTROL; RAS; C-GAMMA-1 AB Phosphoinositide-specific phospholipase C gamma (PLC gamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] forming IP3 and diacylglycerol (DAG) in response to several mitogenic factors, Previously, me determined that microinjected PLC gamma induces DNA synthesis in G(0)-arrested NIH 3T3 cells, suggesting the possibility that PLC gamma mag have an oncogenic potential, In this report, we demonstrate that overexpression of PLC gamma in NIH 3T3 cells results in altered growth properties and cellular transformation, The PLC gamma/3T3 transfectants do not require serum growth factors to proliferate, display anchorage-independent growth in soft agar and induce tumors when transplanted into nude mice. These findings suggest that overexpression of PLC gamma facilitates the transformation of NIH 3T3 cells. Furthermore, PLC gamma expression and activity have been shown to be elevated in many human tumors, Thus, PLC gamma signaling may contribute to the promotion and/or progression of human cancers. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, SAIC Frederick,Intramural Res Support Program, Frederick, MD 21702 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Lab Biochem Physiol, Frederick, MD 21702 USA. RP Smith, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, SAIC Frederick,Intramural Res Support Program, Frederick, MD 21702 USA. EM smithmr@mail.nclfcrf.gov NR 55 TC 29 Z9 31 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 JAN PY 1998 VL 19 IS 1 BP 177 EP 185 DI 10.1093/carcin/19.1.177 PG 9 WC Oncology SC Oncology GA YV095 UT WOS:000071789100023 PM 9472710 ER PT J AU Shibata, MA Jorcyk, CL Devor, DE Yoshidome, K Rulong, S Resau, J Roche, N Roberts, AB Ward, JM Green, JE AF Shibata, MA Jorcyk, CL Devor, DE Yoshidome, K Rulong, S Resau, J Roche, N Roberts, AB Ward, JM Green, JE TI Altered expression of transforming growth factor beta s during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5 ' flanking region fused to SV40 large T antigen SO CARCINOGENESIS LA English DT Article ID STEROID-BINDING-PROTEIN; RECEPTOR MESSENGER-RNA; PROSTATE-CANCER; C-MET; C-3 GENES; TGF-BETA; CARCINOMA; FACTOR-BETA-1; LOCALIZATION; TGF-BETA-1 AB We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans, The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age, Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGF beta s) was evaluated during tumor progression of urethral gland carcinomas, Elevations of intracellular and extracellular TGF beta 1 and extracellular TGF beta 3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGF beta s may augment tumor growth, c-Met expression showed a tendency for increased expression in the urethral gland carcinomas, We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice, Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas, This transgenic mouse model and the cell lines derived from it may pro,ide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer. C1 NCI, Div Basic Sci, Lab Cellular Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Off Lab Anim Sci, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. NCI, ABL, Confocal Microscopy Lab, Frederick, MD 21702 USA. RP Green, JE (reprint author), NCI, Div Basic Sci, Lab Cellular Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. EM JEGreen@nih.gov RI Shen, Rulong/E-4079-2011 NR 51 TC 13 Z9 13 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 JAN PY 1998 VL 19 IS 1 BP 195 EP 205 DI 10.1093/carcin/19.1.195 PG 11 WC Oncology SC Oncology GA YV095 UT WOS:000071789100025 PM 9472712 ER PT J AU Danen, EHJ Lafrenie, RM Miyamoto, S Yamada, KM AF Danen, EHJ Lafrenie, RM Miyamoto, S Yamada, KM TI Integrin signaling: Cytoskeletal complexes, MAP kinase activation, and regulation of gene expression SO CELL ADHESION AND COMMUNICATION LA English DT Article; Proceedings Paper CT 2nd Amsterdam Zoo Meeting on Cell Adhesion and Migration in Inflammation and Cancer CY OCT 22-25, 1997 CL AMSTERDAM, NETHERLANDS SP Cent Lab Netherlands Red Cross Blood Transfus Serv, Royal Netherlands Acad Arts & Sci, KNAW, Dutch Soc Immunol, Dutch Kidney Fdn, Assoc Int Cancer Res-UK, ALZA Corp-USA, Coulter Electr-NL, Cytomat Bio-Instruments GmbH-Germany, Diagnost Prod Corp-NL, Harwood Acad Publshers GmbH-NL, Hercules European Res Ctr-NL, ICOS Corp-USA, Immunex Corp-USA, Immunotech SA-France, Intersens Instruments BV-NL, Laboned-NL, Leukosite-USA, R & D Syst Europe Ltd-UK, Serotec Ltd-UK DE cell adhesion; extracellular matrix; fibronectin; integrin; signal transduction ID FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; FIBRONECTIN RECEPTOR; CYTOPLASMIC DOMAINS; TRANSDUCTION; ANCHORAGE; BINDING; ARCHITECTURE AB Members of the integrin family of adhesion receptors mediate interactions of cells with the extracellular matrix. Besides their role in tissue morphogenesis by anchorage of cells to basement membranes and migration along extracellular matrix proteins, integrins are thought to play a key role in mediating the control of gene expression by the extracellular matrix. Studies over the past 10 years have shown that integrin-mediated cell adhesion can trigger signal transduction cascades involving translocation of proteins and protein tyrosine phosphorylation events. In this review, we discuss approaches used in our lab to study early events in integrin signalling as well as further downstream changes. C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. RP Danen, EHJ (reprint author), NIDR, CDBRB, NIH, Bldg 30,Rm 408,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 46 TC 47 Z9 48 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1998 VL 6 IS 2-3 BP 217 EP 224 DI 10.3109/15419069809004477 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 138KP UT WOS:000076971300016 PM 9823472 ER PT J AU Sud'Ina, GF Galkina, SI Margolis, LB Ullrich, V AF Sud'Ina, GF Galkina, SI Margolis, LB Ullrich, V TI Dependence of neutrophil activation on cell density and adhesion SO CELL ADHESION AND COMMUNICATION LA English DT Article DE adhesive interactions; neutrophil; cell density; 5-lipoxygenase; superoxide production; arachidonic acid ID CORTICAL EPITHELIAL-CELLS; INTRACELLULAR PH; RESPIRATORY BURST; PRIMARY CULTURES; INTEGRINS; LEUKOTRIENE-B4; LYMPHOCYTES; LEUKOCYTES; INHIBITION; MOLECULES AB Upon an increasing cell density human neutrophils develop more cell-to-cell contacts in conjunction with an increase in the pH(i). These changes are accompanied by decreased superoxide formation after adherence, and a decrease in the total amount of 5-lipoxygenase products after various stimuli. Among the various arachidonate metabolites, leukotriene formation remained almost constant but the yield in 5-HETE decreased. This drop in could account for the decrease in total 5-lipoxygenase products observed when the cell density increased. We conclude that cellular signalling can be affected by an increase of cell-cell interactions. Whether the increase in cellular pH is a cause or consequence of such contact inhibition has yet be answered. C1 Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119899, Russia. NICHHD, Theoret & Phys Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Konstanz, Fac Biol, D-78434 Konstanz, Germany. RP Sud'Ina, GF (reprint author), Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119899, Russia. RI Galkina, Svetlana/E-4025-2012; Sud'ina, Galina/E-1053-2012 OI Sud'ina, Galina/0000-0001-7711-3167 NR 28 TC 3 Z9 3 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1998 VL 5 IS 1 BP 27 EP 37 DI 10.3109/15419069809005596 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZN739 UT WOS:000073677100003 PM 9638339 ER PT J AU Medeiros, NA Reese, TS Jaffe, H Degiorgis, JA Bearer, EL AF Medeiros, NA Reese, TS Jaffe, H Degiorgis, JA Bearer, EL TI Primary peptide sequences from squid muscle and optic lobe myosin IIs: A strategy to identify an organelle myosin SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE myosin; squid; organelle; axoplasm; muscle ID HEAVY-CHAIN GENE; AMINO-ACID-SEQUENCE; UNCONVENTIONAL MYOSIN; COMPLETE NUCLEOTIDE; CAENORHABDITIS-ELEGANS; CELLULAR MYOSIN; MESSENGER-RNA; LIGHT-CHAINS; DNA-SEQUENCE; ASSOCIATION AB The squid giant axon provides an excellent model system for the study of actin-based organelle transport likely to be mediated by myosins, but the identification of these motors has proven to be difficult. Here the authors purified and obtained primary peptide sequence of squid muscle myosin as a first step in a strategy designed to identify myosins in the squid nervous system. Limited digestion yielded fourteen peptides derived from the muscle myosin which possess high amino acid sequence identities to myosin II from scallop (60-95%) and chick pectoralis muscle (31-83%). Antibodies generated to this purified muscle myosin were used to isolate a potential myosin from squid optic lobe which yielded 11 peptide fragments. Sequences from six of these fragments identified this protein as a myosin II. The other five sequences matched myosin II (50-60%, identities), and some also matched unconventional myosins (33-50%). A single band that has a molecular weight similar to the myosin purified from optic lobe copurifies with axoplasmic organelles, and, like the optic lobe myosin, this band is also recognized by the antibodies raised against squid muscle myosin II. Hence, this strategy provides an approach to the identification of a myosin associated with motile axoplasmic organelles. (C) 1998 Academic Press. C1 Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Brown Univ, Dept Pathol & Lab Med, Box G, Providence, RI 02912 USA. EM Elaine-Bearer@brown.edu FU NIGMS NIH HHS [R01 GM047368-05, GM47368, R01 GM047368] NR 45 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-6995 EI 1095-8355 J9 CELL BIOL INT JI Cell Biol. Int. PY 1998 VL 22 IS 2 BP 161 EP 173 DI 10.1006/cbir.1998.0248 PG 13 WC Cell Biology SC Cell Biology GA 150VE UT WOS:000077685700010 PM 9878103 ER PT J AU Petralia, RS Rubio, ME Wenthold, RJ AF Petralia, RS Rubio, ME Wenthold, RJ TI Selectivity in the distribution of glutamate receptors in neurons SO CELL BIOLOGY INTERNATIONAL LA English DT Review ID POSTSYNAPTIC DENSITY; COCHLEAR NUCLEUS; AMPA RECEPTORS; PURKINJE-CELLS; MICE LACKING; NMDA; SUBUNITS; SYNAPSES; LOCALIZATION; PROTEINS C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), NIDCD, Neurochem Lab, NIH, 36-5D08,36 Convent Dr MSC 4162, Bethesda, MD 20892 USA. NR 36 TC 7 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 1998 VL 22 IS 9-10 BP 603 EP 608 DI 10.1006/cbir.1998.0385 PG 6 WC Cell Biology SC Cell Biology GA 218WV UT WOS:000081576800001 PM 10452829 ER PT J AU Ashwell, JD AF Ashwell, JD TI When complex worlds collide: retinoic acid and apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Editorial Material ID RESPONSE ELEMENTS; BINDING PROTEIN; THYROID-HORMONE; DIRECT REPEATS; RECEPTORS; RXR; METABOLISM; ACTIVATION; POLARITY; LIGAND C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 1998 VL 5 IS 1 BP 1 EP 3 DI 10.1038/sj.cdd.4400338 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR650 UT WOS:000071516500001 PM 10200439 ER PT J AU Trbovich, AM Hughes, FM Perez, GI Kugu, K Tilly, KI Cidlowski, JA Tilly, JL AF Trbovich, AM Hughes, FM Perez, GI Kugu, K Tilly, KI Cidlowski, JA Tilly, JL TI High and low molecular weight DNA cleavage in ovarian granulosa cells: characterization and protease modulation in intact cells and in cell-free nuclear autodigestion assays SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; DNA cleavage; nucleases; proteases; granulosa cell; follicle; atresia; ovary ID FOLLICLE-STIMULATING-HORMONE; EPIDERMAL GROWTH-FACTOR; DEATH GENE CED-3; CAENORHABDITIS-ELEGANS; INTERLEUKIN-1-BETA-CONVERTING ENZYME; ENDONUCLEASE ACTIVITIES; ICE/CED-3 PROTEASE; CONVERTING-ENZYME; CYSTEINE PROTEASE; SERINE PROTEASE AB To continue elucidation of the biochemical and molecular pathways involved in the induction of apoptosis in granulosa cells (GC) of ovarian follicles destined for atresia, we characterized the occurrence and protease modulation of high and low molecular weight (MW) DNA fragmentation during rat GC death, Atresia of ovarian follicles, occurring either spontaneously in vivo or induced in vitro, was associated with both high MW and internucleosomal (low MW) DNA cleavage, Incubation of follicles in the presence of a putative irreversible and non-competitive inhibitor of caspase-1 (interleukin-1 beta-converting enzyme or ICE), sodium aurothiomalate (SAM), completely prevented internucleosomal, but not high MW, DNA cleavage, As reported previously, morphological features of apoptosis (pyknosis, cellular condensation) and atresia (granulosa cell disorganization, oocyte pseudomaturation) remained detectable in SAM-treated follicles, The potential involvement of proteases in endonuclease activation was further analyzed in cell-free assays using nuclei from both GC (which autodigest their DNA) and HeLa cells (HC, which do not autodigest their DNA un less incubated with extracts prepared from other cell types). Crude cytoplasmic extracts prepared from GC induced both high MW and internucleosomal DNA cleavage in HC nuclei. The induction of low, but not high, MW DNA cleavage in HC nuclei by GC extracts was suppressed by pretreatment of the extracts with SAM or with any one of the serine protease inhibitors, dichloroisocoumarin (DCI), N-tosyl-L-leucylchloromethylketone (TLCK) or N-tosyl-L-phenylchloromethylketone (TPCK). Interestingly, SAM and DCI also prevented cation-induced low MW DNA fragmentation in GC nuclei; however, TLCK and TPCK were without effect. Our results support a role for cytoplasmic and nuclear serine proteases in the activation of the endonuclease(s) responsible for internucleosomal DNA cleavage during apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. NIEHS, Lab Integrat Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 79 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 1998 VL 5 IS 1 BP 38 EP 49 DI 10.1038/sj.cdd.4400299 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR650 UT WOS:000071516500006 PM 10200444 ER PT J AU Coss, MC Stephens, RM Morrison, DK Winterstein, D Smith, LM Simek, SL AF Coss, MC Stephens, RM Morrison, DK Winterstein, D Smith, LM Simek, SL TI The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1 SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; GLUTATHIONE-S-TRANSFERASE; PROTEIN-KINASE; CYCLOSPORINE-A; MAMMALIAN PROTEIN; RECEPTOR COMPLEX; ESCHERICHIA-COLI; PLASMA-MEMBRANE; RAF-1 FUNCTION; BINDING AB FKBP65 is a member of the FK506-binding protein class of immunophilins and is the only member reported to contain four peptidylprolyl cis-trans isomerase domains and an unrelated COOH-terminal domain, In this report, we show that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-l are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of cRaf-1 appears to be required for its interaction with FKBP65. Using GST-FKBP65 fusion protein and purified Raf proteins, we show that full-length FKBP65 can interact with c-Raf-l but not B-Raf, The activation kinetics of c-Raf-l after v-H-Ras(V12) injection of Xenopus oocytes appear to correlate with FKBP65/cRaf-1 interaction, suggesting that FKBP65 may preferentially associate with forms of c-Raf-1 that are more posttranslationally modified. The interaction of FKBP65 with the c-Raf-heat shock protein 90 heterocomplex implicates this immunophilin in signal-transduction processes. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt Immunol,Div Basic Sci, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Appl Biosci Labs, NIH, Frederick, MD 21702 USA. RP Simek, SL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Bldg 560,Room 31-93, Frederick, MD 21702 USA. NR 42 TC 32 Z9 32 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1998 VL 9 IS 1 BP 41 EP 48 PG 8 WC Cell Biology SC Cell Biology GA YR230 UT WOS:000071474000005 PM 9438387 ER PT J AU Wu, XF Kocher, B Wei, Q Hammer, JA AF Wu, XF Kocher, B Wei, Q Hammer, JA TI Myosin Va associates with microtubule-rich domains in both interphase and dividing cells SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE myosin Va; mitotic spindle; midbody; dilute ID UNCONVENTIONAL MYOSIN; CYTOPLASMIC DYNEIN; MITOTIC SPINDLES; GAMMA-TUBULIN; CYTOKINESIS; GENE; LOCALIZATION; MIDBODY; KINETOCHORES; TRANSPORT AB Class V unconventional myosins are two-headed, nonfilamentous, actin-based mechanoenzymes that appear to be expressed ubiquitously. Mice possess at least two myosin V heavy chain genes (dilute and and myr6) whose similar to 190 kDa protein products are referred to as myosin Va and Vb, respectively. Using antibodies that are specific for the Va isoform and immunofluorescence microscopy, we show here that myosin Va localizes to the microtubule organizing center (MTOC) in interphase cells, and to the mitotic asters, spindle, and midbody of dividing cells. These associations, which in the case of mitotic cells are characterized by the concentration of myosin Va in the immediate vicinity of the microtubules, were observed in a variety of cell types. including primary and immortal mouse melanocytes and fibroblasts, Hela cells, and Cos cells. Importantly. these associations were not observed in melanocytes and fibroblasts cultured From dilute null mice, indicating that the staining of these microtubule-rich domains was due to the presence of myosin Va, as opposed to another protein(s) containing a shared epitope(s) with myosin Va. When cells were extracted with detergent prior to fixation, myosin Va remained associated with each of these microtubule-rich domains. suggesting that these associations are not due to the possible presence of membranes at these sites, This Fact, and our observation that these microtubule-rich domains contain little if any F-actin (based on phalloidin staining), suggest that myosin Va may bind to microtubules either directly or through a microtubule-associated protein. Finally, we found that dilute null fibroblasts in primary culture are twice as likely to be binucleate as wild type fibroblasts of the same genetic background (35% vs. 17%). Together, these results indicate that myosin Va associates with microtubule-rich domains in both interphase and dividing cells, and plays a role in the efficiency of cell division in culture. Cell Motil. Cytoskeleton 40:286-303. 1998. a 1998 Wiley-Liss. Inc. C1 NHLBI, Cell Biol Lab, Sect Mol Cell Biol, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, Sect Mol Cell Biol, NIH, Bldg 3,Room B1-22, Bethesda, MD 20892 USA. NR 43 TC 66 Z9 66 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 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1998 VL 40 IS 3 BP 286 EP 303 DI 10.1002/(SICI)1097-0169(1998)40:3<286::AID-CM7>3.0.CO;2-B PG 18 WC Cell Biology SC Cell Biology GA ZX218 UT WOS:000074491200007 PM 9678671 ER PT J AU Moncman, CL Wang, K AF Moncman, CL Wang, K TI Effects of thiol protease inhibitors on myoblast fusion and myofibril assembly in vitro SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE integrins; dystrophin; myofibril assembly; myoblast fusion; confocal microscopy ID SKELETAL-MUSCLE CELLS; FIBER-LIKE STRUCTURES; MYOGENIC DIFFERENTIATION; CYTOPLASMIC DOMAINS; NASCENT MYOFIBRILS; CARDIAC MYOCYTES; MUCOLIPIDOSIS-II; ACTIN-FILAMENTS; GENE-EXPRESSION; ALPHA-ACTININ AB To investigate the roles of thiol proteases such as cathepsins and calpains in muscle differentiation, we have treated primary cultures of pectoralis muscle with a variety of protease inhibitors and examined the effects these agents have on myoblast fusion and myofibrillogenesis. We have found that a membrane-permeable inhibitor, E64D, has dramatic effects on both events of muscle differentiation. Cells treated with this inhibitor display gross morphological changes, severe delays in myofibril assembly, and reduced ability to fuse in culture. These morphological changes are correlated with a build up of beta 1-integrin throughout the cytoplasm. These effects could also be produced using NH4Cl, a lysosomotrophic agent. In addition, we show that two nonpermeable inhibitors (leupeptin and E64) slightly decrease myoblast fusion, but have no effects on the ability of the cells to form mature myofibrils. These results are discussed in terms of their relevance to the inheritable disease of muscular dystrophy and I-cell disease (mucolipodosis II). Cell Motil. Cytoskeleton 40:354-367, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Texas, Inst Biochem, Dept Chem & Biochem, Austin, TX USA. Univ Texas, Cell Res Inst, Austin, TX USA. RP Wang, K (reprint author), IAMS, NIH, Bldg 6,Rm 401, Bethesda, MD 20892 USA. NR 63 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1998 VL 40 IS 4 BP 354 EP 367 DI 10.1002/(SICI)1097-0169(1998)40:4<354::AID-CM4>3.0.CO;2-B PG 14 WC Cell Biology SC Cell Biology GA 106NF UT WOS:000075135100004 PM 9712265 ER PT J AU Bubb, MR Baines, IC Kom, ED AF Bubb, MR Baines, IC Kom, ED TI Localization of actobindin, profilin I, profilin II, and phosphatidylinositol-4,5-bisphosphate (PIP2) in Acanthamoeba castellanii SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE actin monomer-binding proteins; immunomicroscopy; lamellipodia; plasma membrane ID G-ACTIN; PHOSPHOINOSITIDE METABOLISM; BINDING PROTEIN; F-ACTIN; ISOFORMS; PURIFICATION; ACTOPHORIN; PLATELET; CELLS; SITE AB Specific polyclonal antisera were raised against purified Acanthamoeba actobindin and synthetic peptides corresponding to regions of maximum charge differences in Acanthamoeba profilin I and profilin II. Immunofluorescence studies with these antibodies showed profilin I to be distributed throughout the Acanthamoeba cytoplasm, except for lamellipodia, with the highest fluorescence intensity in cortical regions in which monomeric actin also was present, as shown by labeling with fluorescent DNase. In contrast, profilin II appeared to be uniformly associated with the plasma membrane except at sites of pseudopod extension, where the concentration was frequently decreased, in addition to cortical regions. Immunofluorescence studies using a monoclonal antibody specific for phosphatidylinositol-4,5-bisphosphate (PIP2) suggested that its distribution is mostly limited to the plasma membrane, In contrast to the distribution of profilin IT, PIP2 immunofluorescence was prominent at the leading edge of cells, including the plasma membrane of lamellipodia. Quantitative immunoelectron microscopy showed that profilin II was approximately 36 times more Likely to localize to the plasma membrane than profilin I. Immunofluorescence and confocal microscopy localized actobindin to the base of lamellipodia. The differential localization of the three actin monomer-binding proteins suggests that they have different biologic functions in Acanthamoeba and is consistent with the hypotheses that (1) profilin I functions predominantly as an actin monomer-binding protein; (2) profilin II regulates, or is regulated by, PIP2; and (3) actobindin inhibits nucleation of new filaments and facilitates elongation of existing polarized filaments in actively motile regions. (C) 1998 Wiley-Liss, Inc. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kom, ED (reprint author), NHLBI, Cell Biol Lab, NIH, 9000 Rockville Pike,3 Ctr Dr,MSC 0301, Bethesda, MD 20892 USA. NR 48 TC 26 Z9 27 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1998 VL 39 IS 2 BP 134 EP 146 DI 10.1002/(SICI)1097-0169(1998)39:2<134::AID-CM4>3.0.CO;2-6 PG 13 WC Cell Biology SC Cell Biology GA YV224 UT WOS:000071801800004 PM 9484955 ER PT J AU Cheng, HR Fraidakis, M Blomback, B Lapchak, P Hoffer, B Olson, L AF Cheng, HR Fraidakis, M Blomback, B Lapchak, P Hoffer, B Olson, L TI Characterization of a fibrin glue-GDNF slow-release preparation SO CELL TRANSPLANTATION LA English DT Article DE fibrin glue; GDNF; slow release; spinal cord ID PERIPHERAL REGENERATION CHAMBERS; FIBRONECTIN-CONTAINING MATRIX; DEVELOPING DOPAMINE NEURONS; PLASMA CLOT LYSIS; NEUROTROPHIC FACTOR; BINDING SITE; IN-VIVO; GROWTH; HEPARIN; NERVE AB One novel method to deliver trophic factor locally in the CNS is to mix it into fibrin glue, In the present studies, [(125)I]-labeled GDNF-containing fibrin glue balls were used to determine binding and spread of the trophic factor, First, the binding of different concentrations of [(125)I]-labeled GDNF in fibrin glue was determined in vitro., Within the six concentrations used (from 200 nM to 0.004 nM, 0 M as control), there was a strong linear correlation between the [(125)I]-GDNF concentration and the recovered radioactivity (r = 0.992), The mean bound radioactivity in 16 samples with 4 nM [(125)I]-GDNF was 71262 +/- 2710 CPM, and accounted for 89.8% of the mean initial count of free [(I25)I]-GDNF (79369 +/- 3499 CPM). Second, [(125)I]-GDNF-containing glue balls were implanted into the anterior chamber of adult rats, The implanted fibrin glue balls decreased in size with time, but could still be identified on the irises 2 wk after implantation, Radioactivity was concentrated at the implantation sites in the early stages with a distribution in the surrounding iris tissue, which became separated into focal radioactive spots at the third week, Counts of radioactivity were significantly higher, in the [(125)I]-GDNF glue ball-implanted irises than controls until 14 days after implantation, A study of the [(125)I] decay over time using least-squares linear regression demonstrated first-order kinetics (r = -0.98, p <0.02) with k = 0.0091 and T 1/2 = 76 h., Finally, [(I25)I]-GDNF-containing glue balls were implanted in the spinal cord of adult rats, Radioactivity was concentrated at the implantation sites in the early stages and was later distributed more widely in the surrounding thoracic cord, The [(125)I]-GDNF-containing glue. degraded over time and became a porous meshwork. with decreasing radioactivity at the later time points; Radioactivity in the spinal cords subjected to implantation of [(125)I]-GDNP-containing glue balls was higher than iri controls for 14 days, Study of the [(125)I] decay by time with least-squares linear regression demonstrated first-order kinetics (r = -0.97, p = 0.001) with T 1/2 = 75.6 h., We conclude that the trophic factor GDNF becomes bound in the fibrin glue matrix from which it is gradually released, Our results suggest that fibrin glue is an effective substrate for keeping a trophic factor localized in situ for a finite period, protected from the circulation, surrounding aqueous humor or CSF, (C) 1998 Elsevier Science Inc,. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Karolinska Inst, Dept Coagulat Res, S-17177 Stockholm, Sweden. Amgen Inc, Thousand Oaks, CA 91320 USA. NIDA, NIH, Baltimore, MD 21224 USA. Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Taipei, Taiwan. Natl Yang Ming Univ, Div Surg, Taipei 11217, Taiwan. RP Olson, L (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. OI Lapchak, Paul/0000-0003-4413-7554 NR 42 TC 30 Z9 30 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 1998 VL 7 IS 1 BP 53 EP 61 DI 10.1016/S0963-6897(97)00122-X PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA YX067 UT WOS:000072003100006 PM 9489763 ER PT J AU Kultz, D Burg, MB AF Kultz, D Burg, MB TI Intracellular signaling in response to osmotic stress SO CELL VOLUME REGULATION SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASES; CELL-VOLUME REGULATION; IMMEDIATE-EARLY GENE; RHO-FAMILY GTPASES; MAP KINASE; ALDOSE REDUCTASE; TRANSCRIPTION FACTORS; HYPEROSMOTIC STRESS; ESCHERICHIA-COLI; MAMMALIAN-CELLS C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Kultz, D (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,MSC 1603, Bethesda, MD 20892 USA. EM mburg@nih.gov NR 70 TC 27 Z9 27 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 1998 VL 123 BP 94 EP 109 DI 10.1159/000059923 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA BL70S UT WOS:000076407800007 PM 9761963 ER PT J AU Horton, JK Vanoye, CG Reuss, L AF Horton, JK Vanoye, CG Reuss, L TI Swelling-activated chloride currents in a drug-sensitive cell line and a P glycoprotein-expressing derivative are underlied by channels with the same pharmacological properties SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE multidrug resistance; P glycoprotein; chloride channels ID MULTIDRUG-RESISTANT CELLS; PLASMA-MEMBRANE; CYSTIC-FIBROSIS; CL CHANNEL; VOLUME; TRANSPORT; ATP; CYTOSKELETON; REGULATOR; CFTR AB It has been proposed that P glycoprotein (Pgp) expression is associated with swelling-activated Cl- currents in multidrug-resistant cells. The Pgp substrate vinblastine and the modulator verapamil produced a reversible concentration-dependent block of swelling-activated Cl- currents in both a drug-sensitive cell line (MCF-7) and a Pgp-expressing derivative (BC19/3), The similarity of the results obtained in both cell lines suggests that the mechanism of block is not related to Pgp expression and supports the hypothesis that Pgp expression is not necessary for the swelling activation of Cl- currents. In contrast to the results obtained with vinblastine, two other cytoskeleton-disrupting agents, colchicine and cytochalasin D, were not able to affect the swelling-activated Cl- currents in either cell line, The data provided Ilo evidence for the involvement of the cytoskeleton in the swelling activation of Cl- channels in these cell lines. The Cl- channel blockers, 5-nitro-2-(3-phenylpropylamino)benzoic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, each produced a similar reversible concentration-dependent block in the swelling-activated currents in both the Pgp-expressing and nonexpressing cells, This strongly suggests that the Cl- channel(s) responsible for the swelling-dependent current in both cell lines are the same and, since MCF-7 cells do not express Pgp, that Pgp is not the channel responsible for the volume-activated Cl- currents in these cells. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77550 USA. RP Horton, JK (reprint author), NIEHS, Struct Biol Lab, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 42 TC 16 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 1998 VL 8 IS 5 BP 246 EP 260 DI 10.1159/000016287 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 138BT UT WOS:000076952100002 PM 9792953 ER PT J AU Auburger, G AF Auburger, G TI New genetic concepts and stroke prevention SO CEREBROVASCULAR DISEASES LA English DT Article; Proceedings Paper CT 7th European Stroke Conference CY MAY 29, 1998 CL EDINBURGH, SCOTLAND SP Sanofi, Bristol-Myers Squibb DE stroke; linkage; QTL; genes ID CEREBRAL CAVERNOUS MALFORMATION; FAMILIAL HEMIPLEGIC MIGRAINE; CEREBROVASCULAR-DISEASE; HUMAN HYPERTENSION; MISSENSE MUTATION; NOTCH3 MUTATIONS; BLOOD-PRESSURE; ADULT-ONSET; LOCUS; HEMORRHAGE AB So far, stroke genetics has the reputation of daunting complexity and heterogeneity. However, progress through efforts at studying the human genome has provided novel technologies and focus, and 12 stroke genes or loci have already been identified in the last years, usually through the study of large pedigrees. However, particularly little is known about the ischemic form of stroke, and only recently could one chromosomal locus be shown to exert a major effect on stroke latency and outcome - through QTL studies in mouse strains. Whether the outstanding role of this one gene locus is also true in humans should be tested in linkage analyses of large pedigrees. The characterization of such families will probably be essential for progress in molecular genetics of ischemic stroke as well as being a challenge for clinical stroke centers. C1 Natl Human Genome Res Inst, LAB 49 3A18, NIH, Bethesda, MD 20892 USA. Univ Hosp Dusseldorf, Dept Neurol, Dusseldorf, Germany. RP Auburger, G (reprint author), Natl Human Genome Res Inst, LAB 49 3A18, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM auburger@nhgri.nih.gov NR 50 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 1998 VL 8 SU 5 BP 28 EP 32 DI 10.1159/000047515 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 136YP UT WOS:000076886900004 PM 9767196 ER PT S AU McPhie, P AF McPhie, P BE Brown, F Lubiniecki, A Murano, G TI Estimation of secondary/tertiary structure SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res ID CIRCULAR-DICHROISM SPECTRA; TERTIARY STRUCTURE CLASS; CONFORMATION; PROTEINS AB A protein has three types of structure: primary, its covalent sequence; secondary, the local arrangement of the polypeptide chain; tertiary, the mutual three-dimensional arrangement of the chain. Two spectroscopic techniques allow convenient estimation of the amount and type of secondary structure in a pure protein. Analysis of the Fourier Transform infra Red Spectrum of the Amide I band of a protein (1650 cm(-1)) allows direct evaluation of the relative amounts of the peptide groups in various secondary structures. The Circular Dichroism Spectrum of the peptide chromophore (below 240 nm) can yield similar information and may allow assignment of the protein in one of five general structural classes. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP McPhie, P (reprint author), NIDDKD, NIH, 9000 Rockville Pike,Bldg 8,Rm 215, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 29 EP 36 PG 8 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000004 PM 9890513 ER PT S AU Grzesiek, S AF Grzesiek, S BE Brown, F Lubiniecki, A Murano, G TI Structural characterization of proteins by NMR SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res ID BACKBONE ASSIGNMENTS; SECONDARY STRUCTURE; C-13; H-1 C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Grzesiek, S (reprint author), NIDDKD, NIH, Bldg 5,Rm BI-27, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 37 EP 41 PG 5 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000005 PM 9890514 ER PT S AU Wingfield, P AF Wingfield, P BE Brown, F Lubiniecki, A Murano, G TI Characterization of biotechnology pharmaceutical products - Summary of day one SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 NIH, Bethesda, MD 20892 USA. RP Wingfield, P (reprint author), NIH, 9000 Rockville Pike,Bldg 6B-1B130, 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 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 183 EP 186 PG 4 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000032 ER PT J AU Bies, J Feikova, S Wolff, L AF Bies, J Feikova, S Wolff, L TI Proteolysis of the transcription factor c-Myb by the 26S proteasome SO CHEMICAL PAPERS LA English DT Article; Proceedings Paper CT XVI Biochemical Congress of the Slovak-and-Czech-Society-of-Biochemistry-and-Molecular-Biology CY OCT 12-15, 1998 CL STARA LESNA, SLOVAKIA SP Slovak & Czech Soc Biochem & Molec Biol C1 Slovak Acad Sci, Canc Res Inst, Dept Mol Virol, Bratislava, Slovakia. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Bies, J (reprint author), Slovak Acad Sci, Canc Res Inst, Dept Mol Virol, Bratislava, Slovakia. NR 3 TC 0 Z9 0 U1 0 U2 0 PU VERSITA PI WARSAW PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND SN 0366-6352 J9 CHEM PAP JI Chem. Pap. PY 1998 VL 52 SI SI BP 250 EP 250 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 133DT UT WOS:000076671700005 ER PT J AU Bystricky, S Kossaczka, Z Szu, SC AF Bystricky, S Kossaczka, Z Szu, SC TI Polysaccharide - Protein conjugates for prevention of bacterial diseases SO CHEMICAL PAPERS LA English DT Article; Proceedings Paper CT XVI Biochemical Congress of the Slovak-and-Czech-Society-of-Biochemistry-and-Molecular-Biology CY OCT 12-15, 1998 CL STARA LESNA, SLOVAKIA SP Slovak & Czech Soc Biochem & Molec Biol ID HYPOTHESIS C1 Slovak Acad Sci, Inst Chem, Bratislava, Slovakia. NICHD, NIH, Bethesda, MD USA. RP Bystricky, S (reprint author), Slovak Acad Sci, Inst Chem, Bratislava, Slovakia. NR 5 TC 0 Z9 0 U1 0 U2 0 PU VERSITA PI WARSAW PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND SN 0366-6352 J9 CHEM PAP JI Chem. Pap. PY 1998 VL 52 SI SI BP 358 EP 358 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 133DT UT WOS:000076671700097 ER PT J AU Szeliga, J Dipple, A AF Szeliga, J Dipple, A TI DNA adduct formation by polycyclic aromatic hydrocarbon dihydrodiol epoxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID COVALENT NUCLEOSIDE ADDUCTS; BENZOPYRENE 7,8-DIOL 9,10-EPOXIDES; REGION 3,4-DIOL 1,2-EPOXIDES; CELL-LINE MCF-7; MOUSE SKIN; METABOLIC-ACTIVATION; DIOL EPOXIDES; CHEMICAL CARCINOGENESIS; 11,12-DIHYDRODIOL 13,14-EPOXIDE; DEOXYRIBONUCLEIC ACID C1 NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Dipple, A (reprint author), NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 67 TC 177 Z9 179 U1 0 U2 6 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 JAN PY 1998 VL 11 IS 1 BP 1 EP 11 DI 10.1021/tx970142f PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA YT609 UT WOS:000071624200001 PM 9477220 ER PT J AU Barlow, T Dipple, A AF Barlow, T Dipple, A TI Aralkylation of guanosine with para-substituted styrene oxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REACTION-PRODUCTS; DNA; SELECTIVITY; ALKYLATION; ADDUCTS; SITES AB To probe mechanisms of nucleoside aralkylation, product distributions and product stereochemistries were determined in reactions of optically active p-methyl-and p-bromostyrene oxide with guanosine. The proportion of 7-, N-2- and O-6-substituted guanosine products was similar to 0.32:0.62:0.06 in neutral, aqueous reactions with the (R)-p-methylstyrene oxide and similar to 0.85: 0.09:0.04 in reactions with the (R)-p-bromostyrene oxide. The exocyclic positions opened the epoxide at the alpha-carbon. Epoxide ring opening by the nitrogen at the 7-position showed little preference for the alpha- or beta-carbons in reactions with p-methylstyrene oxide. However, the p-bromostyrene oxide favored reaction at the beta-carbon almost 4-fold over reaction at the alpha-carbon. Almost total inversion of stereochemistry was found to occur in reactions at the 7-position. In contrast, the ratio of inversion to retention of configuration in N-2- and O-6-substituted products was similar to 2:1 and similar to 1:1 for reactions with the p-methylstyrene oxide and similar to 6:1 and similar to 3:1 for reactions with p-bromostyrene oxide, respectively. These experiments suggest that an S(N)2 mechanism is in effect with reactions at the 7-position, whereas substrates of an increasingly ionic nature are involved in reactions at the N-2- and O-6-positions, respectively. C1 NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Barlow, T (reprint author), NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 35 TC 17 Z9 17 U1 0 U2 0 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 JAN PY 1998 VL 11 IS 1 BP 44 EP 53 DI 10.1021/tx970126i PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA YT609 UT WOS:000071624200006 PM 9477225 ER PT J AU Beard, WA Wilson, SH AF Beard, WA Wilson, SH TI Structural insights into DNA polymerase beta fidelity: hold tight if you want it right SO CHEMISTRY & BIOLOGY LA English DT Article ID REPLICATION; MECHANISM; BINDING AB DNA polymerases must select and incorporate the correct deoxynucleoside 5'-triphosphate from a pool of structurally similar molecules. The structural and kinetic characterization of DNA polymerase beta indicates that this polymerase must stabilize the templating base to achieve efficient polymerization with high fidelity. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Beard, WA (reprint author), NIEHS, Struct Biol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 27 TC 58 Z9 60 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 1998 VL 5 IS 1 BP R7 EP R13 DI 10.1016/S1074-5521(98)90081-3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YX275 UT WOS:000072023900003 PM 9479474 ER PT B AU Sternberg, KJ Lamb, ME Dawud-Noursi, S AF Sternberg, KJ Lamb, ME Dawud-Noursi, S BE Holden, GW Geffner, R Jouriles, EN TI Using multiple informants to understand domestic violence and its effects SO CHILDREN EXPOSED TO MARITAL VIOLENCE: THEORY, RESEARCH, AND APPLIED ISSUES LA English DT Proceedings Paper CT 1st International Conference on Children Exposed to Marital Violence CY JUN 06-08, 1996 CL AUSTIN, TX SP Amer Psychol Assoc, RGK Fdn, Hogg Fdn ID CHILD-BEHAVIOR; MARITAL VIOLENCE; MALTREATMENT; PERCEPTIONS; ADJUSTMENT; PARENTS; ATTRIBUTIONS; DEPRESSION; AGGRESSION; SYMPTOMS C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD USA. NR 53 TC 37 Z9 37 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST STREET NE, WASHINGTON, DC 20002 USA BN 1-55798-472-7 PY 1998 BP 121 EP 156 DI 10.1037/10257-004 PG 36 WC Psychology, Clinical; Family Studies; Psychiatry; Psychology; Psychology, Social; Social Work; Sociology SC Psychology; Family Studies; Psychiatry; Social Work; Sociology GA BM31C UT WOS:000078348500005 ER PT B AU Suchy, SF Nussbaum, RL AF Suchy, SF Nussbaum, RL BE Zeisel, SH Szuhaj, BF TI Lowe syndrome: A human inborn error of phosphatidylinositol metabolism SO CHOLINE, PHOSPHOLIPIDS, HEALTH, AND DISEASE LA English DT Proceedings Paper CT 7th International Congress on Phospholipids CY SEP, 1996 CL BRUSSELS, BELGIUM SP Archer Daniels Midland, Avanti Polar Lipids Inc, Cent Soya Co Inc, Lucas Meyer GmbH, Nattermann Phospholipid GmbH, N V Vamo Mills Protein & Lecithin Div, Riceland Foods ID OCULOCEREBRORENAL SYNDROME; ACID PHOSPHOLIPIDS; 4,5-BISPHOSPHATE; GENE; PHOSPHOINOSITIDES; MUTATIONS; PROTEIN; GOLGI; PHOSPHORYLATION; 5-KINASE C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Suchy, SF (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 508 S 6TH ST, CHAMPAIGN, IL 61820 USA BN 0-935315-86-1 PY 1998 BP 92 EP 99 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BM62C UT WOS:000079285800009 ER PT B AU Ostrowski, LE Andrews, KL Potdar, PD Nettesheim, P AF Ostrowski, LE Andrews, KL Potdar, PD Nettesheim, P BE Baum, GL Priel, Z Roth, Y Liron, N Ostfeld, E TI Regulation of ciliogenesis and ciliated cell specific genes SO CILIA, MUCUS, AND MUCOCILIARY INTERACTIONS LA English DT Proceedings Paper CT International Congress on Cilia, Mucus, and Mucociliary Interactions, in Honor of Professor Alex Silberberg CY FEB 23-27, 1997 CL JERUSALEM, ISRAEL SP Amer Coll Chest Physicians, Ben Gurion Univ Negev, Israel, Canada Int Sci Exchange Program, Canadian Soc Otolaryngol Head & Neck Surg, European Resp Soc, European Rhinol Soc, Hebrew Univ, Jerusalem, Inst Nose & Sinus Therapy & Clin Investigat, Wolfson Med Ctr, Israel, Technion Israel Inst Technol, Israel Soc Otolaryngol Head & Neck Surg, Israel Soc pulmonol, Tel Aviv Univ, Israel, Weizman Inst Sci, Israel C1 NIH, Res Triangle Pk, NC USA. RP Ostrowski, LE (reprint author), NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA BN 0-8247-0138-0 PY 1998 BP 43 EP 47 PG 5 WC Cell Biology; Materials Science, Biomaterials; Otorhinolaryngology; Physiology; Respiratory System SC Cell Biology; Materials Science; Otorhinolaryngology; Physiology; Respiratory System GA BK55J UT WOS:000072555400006 ER PT B AU Nettesheim, P Guzman, K Koo, JS Yoon, JY Gray, T AF Nettesheim, P Guzman, K Koo, JS Yoon, JY Gray, T BE Baum, GL Priel, Z Roth, Y Liron, N Ostfeld, E TI Regulation of differentiation and mucin secretion in tracheobronchial epithelial cell cultures SO CILIA, MUCUS, AND MUCOCILIARY INTERACTIONS LA English DT Proceedings Paper CT International Congress on Cilia, Mucus, and Mucociliary Interactions, in Honor of Professor Alex Silberberg CY FEB 23-27, 1997 CL JERUSALEM, ISRAEL SP Amer Coll Chest Physicians, Ben Gurion Univ Negev, Israel, Canada Int Sci Exchange Program, Canadian Soc Otolaryngol Head & Neck Surg, European Resp Soc, European Rhinol Soc, Hebrew Univ, Jerusalem, Inst Nose & Sinus Therapy & Clin Investigat, Wolfson Med Ctr, Israel, Technion Israel Inst Technol, Israel Soc Otolaryngol Head & Neck Surg, Israel Soc pulmonol, Tel Aviv Univ, Israel, Weizman Inst Sci, Israel C1 NIH, Res Triangle Pk, NC USA. RP Nettesheim, P (reprint author), NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA BN 0-8247-0138-0 PY 1998 BP 137 EP 142 PG 6 WC Cell Biology; Materials Science, Biomaterials; Otorhinolaryngology; Physiology; Respiratory System SC Cell Biology; Materials Science; Otorhinolaryngology; Physiology; Respiratory System GA BK55J UT WOS:000072555400016 ER PT J AU Jenkins, GM Crow, MT Bilato, C Gluzband, Y Ryu, WS Li, ZH Stetler-Stevenson, W Nater, C Froehlich, JP Lakatta, EG Cheng, L AF Jenkins, GM Crow, MT Bilato, C Gluzband, Y Ryu, WS Li, ZH Stetler-Stevenson, W Nater, C Froehlich, JP Lakatta, EG Cheng, L TI Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries SO CIRCULATION LA English DT Article DE restenosis; neointima; extracellular matrix; metalloproteinases; carotid arteries ID LUMINAL CORONARY ANGIOPLASTY; SMOOTH-MUSCLE CELLS; IV COLLAGENASE; TISSUE INHIBITOR; TUMOR INVASION; EXTRACELLULAR-MATRIX; INTIMAL HYPERPLASIA; VASCULAR INJURY; FOLLOW-UP; RESTENOSIS AB Background-Remodeling of the injured vascular wall is dependent on the action of several extracellular proteases. Previous studies have shown that expression of matrix metalloproteinases (MMP-2 and MMP-9) is upregulated after vascular injury and that MMP-2 is required for the migration of cultured vascular smooth muscle cells across complex extracellular matrix barriers. The present study examined changes ill the expression of membrane-type metalloproteinase (MT-MMP-1), a putative regulator of MMP-2, in the tissue localization of MMP-2, and in the expression of activated and latent forms of MMP-2 and the tissue inhibitor of metalloproteinases, TIMP-2, in rat carotid arteries subjected to balloon catheter injury. Methods and Results-MT-MMP-1 mRNA levels increased sixfold after 3 days of injury, coinciding with an increase in MMP-2 activation assessed by gelatin zymography. Western blotting and gelatin zymography showed an increase in MMP-2 protein levels beginning 5 to 7 days after injury; immunocytochemistry and Western blotting showed that the increase occurred preferentially in the developing neointima. Conclusions-These results show that increased expression of MT-MMP-1 and activation of MMP-2 occurs early after injury to the rat carotid artery and that at later times MMP-2 is preferentially localized to the developing neointima. C1 NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, NCI, Pathol Lab, Baltimore, MD 21224 USA. RP Crow, MT (reprint author), NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM CROWM@GRC.NIA.NIH.GOV RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 56 TC 80 Z9 90 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN PY 1998 VL 97 IS 1 BP 82 EP 90 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YQ244 UT WOS:000071365900016 PM 9443435 ER PT J AU Sussman, MA Baque, S Uhm, CS Daniels, MP Price, RL Simpson, D Terracio, L Kedes, L AF Sussman, MA Baque, S Uhm, CS Daniels, MP Price, RL Simpson, D Terracio, L Kedes, L TI Altered expression of tropomodulin in cardiomyocytes disrupts the sarcomeric structure of myofibrils SO CIRCULATION RESEARCH LA English DT Article DE tropomodulin; actin; sarcomere; myofibril; cardiac, heart ID CHICK CARDIAC MYOCYTES; THIN FILAMENT LENGTH; ACTIN-FILAMENTS; POINTED ENDS; MUSCLE; PROTEIN; TROPOMYOSIN; NEBULIN; GROWTH; CELLS AB Tropomodulin is a tropomyosin-binding protein that terminates "pointed-end" actin filament polymerization. To test the hypothesis that regulation of tropomoduliniactin filament stoichiometry is critical for maintenance of actin filament length, tropomodulin levels were altered in cells by infection with recombinant adenoviral expression vectors, which produce either sense or antisense tropomodulin mRNA. Neonatal rat cardiomyocytes were infected, and sarcomeric actin filament organization was examined. Confocal microscopy indicated that overexpression of tropomodulin protein shortened actin filaments and caused myofibril degeneration. In contrast, decreased tropomodulin content resulted in the formation of abnormally long actin filament bundles. Despite changes in myofibril structure caused by altered tropomodulin expression, total protein turnover of the cardiomyocytes was unaffected. Biochemical analyses of infected cardiomyocytes indicated that changes in actin distribution, rather than altered actin content, accounted for myofibril reorganization. Ultrastructural analysis showed thin-filament disarray and revealed the presence of leptomeres after tropomodulin overexpression. Tropomodulin-mediated effects constitute a novel mechanism to control actin filaments, and our findings demonstrate that regulated tropomodulin expression is necessary to maintain stabilized actin filament structures in cardiac muscle cells. C1 Univ So Calif, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA USA. Univ So Calif, Sch Med, Inst Med Genet, Los Angeles, CA USA. Univ Barcelona, Dept Physiol & Biochem, E-08007 Barcelona, Spain. NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. Univ S Carolina, Sch Med, Dept Anat & Dev Biol, Columbia, SC USA. RP Sussman, MA (reprint author), Childrens Hosp & Res Fdn, Div Mol Cardiovasc Biol, Room 3033,3333 Burnet Ave, Cincinnati, OH 45249 USA. EM sussman@heart.chn1cc.org NR 35 TC 92 Z9 92 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JAN PY 1998 VL 82 IS 1 BP 94 EP 105 PG 12 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA YT087 UT WOS:000071562700011 PM 9440708 ER PT B AU Martinez, A AF Martinez, A BE Martinet, Y Hirsch, FR Martinet, N Vignaud, JM Mulshine, JL TI Application of in situ PCR and in situ hybridization to the characterization of lung cancers SO CLINICAL AND BIOLOGICAL BASIS OF LUNG CANCER PREVENTION SE RESPIRATORY PHARMACOLOGY AND PHARMACOTHERAPY LA English DT Proceedings Paper CT Workshop on Prevention and Early Detection of Lung Cancer CY JUN 22-25, 1996 CL HELSINGOR, DENMARK SP Int Assoc Study Lung Canc C1 NCI, Cell & Canc Biol Dept, NIH, Rockville, MD 20580 USA. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Dept, NIH, 9610 Med Ctr Dr, Rockville, MD 20580 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5778-9 J9 RESP PHARM & PHARMAC PY 1998 BP 67 EP 73 PG 7 WC Oncology; Pharmacology & Pharmacy; Respiratory System SC Oncology; Pharmacology & Pharmacy; Respiratory System GA BK39D UT WOS:000071971200006 ER PT B AU Wang, XW Greenblatt, MS Harris, CC AF Wang, XW Greenblatt, MS Harris, CC BE Martinet, Y Hirsch, FR Martinet, N Vignaud, JM Mulshine, JL TI Molecular genetics of lung cancer SO CLINICAL AND BIOLOGICAL BASIS OF LUNG CANCER PREVENTION SE RESPIRATORY PHARMACOLOGY AND PHARMACOTHERAPY LA English DT Proceedings Paper CT Workshop on Prevention and Early Detection of Lung Cancer CY JUN 22-25, 1996 CL HELSINGOR, DENMARK SP Int Assoc Study Lung Canc C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5778-9 J9 RESP PHARM & PHARMAC PY 1998 BP 117 EP 127 PG 11 WC Oncology; Pharmacology & Pharmacy; Respiratory System SC Oncology; Pharmacology & Pharmacy; Respiratory System GA BK39D UT WOS:000071971200010 ER PT B AU Kroog, GS Hellmich, MR Akeson, MA Jensen, RT Northup, JK Battey, JF AF Kroog, GS Hellmich, MR Akeson, MA Jensen, RT Northup, JK Battey, JF BE Martinet, Y Hirsch, FR Martinet, N Vignaud, JM Mulshine, JL TI In vitro analysis of bombesin/gastrin-releasing peptide receptor (bb2) ligand binding and G-protein coupling SO CLINICAL AND BIOLOGICAL BASIS OF LUNG CANCER PREVENTION SE RESPIRATORY PHARMACOLOGY AND PHARMACOTHERAPY LA English DT Proceedings Paper CT Workshop on Prevention and Early Detection of Lung Cancer CY JUN 22-25, 1996 CL HELSINGOR, DENMARK SP Int Assoc Study Lung Canc AB Bombesin/gastrin releasing peptide receptors (GRP-R, or bb2) mediate a broad spectrum of biological responses including secretion of other peptide hormones, gastric acid secretion, smooth muscle contraction, modulation of neuron firing rate, and growth regulation of both normal and neoplastic cells. Of particular interest, bombesin and its receptor have been shown to promote the growth of some human lung carcinoma cells by an autocrine mechanism, a phenomenon that is thought to play a pivotal role in the pathogenesis and progression of these tumors. These observations make the bb2 receptor a potentially important target for early intervention and prevention strategies. To develop these strategies, it is essential to understand the initial events in receptor mediated signal transduction: ligand binding and activation of G(q), a cognate heterotrimeric G protein for this receptor We have developed in vitro assays for both ligand binding and G protein activation, which allow a quantitative analysis of the molecular pharmacology of both processes. In addition to providing important insights into the pharmacology of bb2, these in vitro assays provide a means to evaluate the utility and efficacy of compounds or drugs which may interfere with ligand binding and/or receptor/G-protein coupling. C1 Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Battey, JF (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, 5 Res Court Room 2B28, Rockville, MD 20850 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5778-9 J9 RESP PHARM & PHARMAC PY 1998 BP 143 EP 156 PG 14 WC Oncology; Pharmacology & Pharmacy; Respiratory System SC Oncology; Pharmacology & Pharmacy; Respiratory System GA BK39D UT WOS:000071971200012 ER PT B AU Mulshine, JL De Luca, LM Dedrick, RL AF Mulshine, JL De Luca, LM Dedrick, RL BE Martinet, Y Hirsch, FR Martinet, N Vignaud, JM Mulshine, JL TI Regional delivery of retinoids: A new approach to early lung cancer intervention SO CLINICAL AND BIOLOGICAL BASIS OF LUNG CANCER PREVENTION SE RESPIRATORY PHARMACOLOGY AND PHARMACOTHERAPY LA English DT Proceedings Paper CT Workshop on Prevention and Early Detection of Lung Cancer CY JUN 22-25, 1996 CL HELSINGOR, DENMARK SP Int Assoc Study Lung Canc AB Currently, most new lung cancers are found only after symptoms or signs reflect the occurrence of regional or distant metastases. Delayed awareness of lung cancer accounts for its 87% five year mortality rate. New insights may lead to improved methods of early lung cancer detection. Experimental intervention proposed for early cancer management generally entails the oral administration of chemoprevention agents. In this chapter, we discuss an alternative delivery strategy using direct aerosol delivery. The model chemoprevention agents for this discussion are the vitamin A analogues. Preliminary clinical reports suggest benefit in reducing the frequency of new lung cancers for previously resected non-small cell lung cancer patients as well as treated head and neck cancer patients. Chronic oral administration of retinoids is problematic due to the frequency of debilitating side effects. Alternatively, by delivering retinoids directly to the airways as an aerosol, the first-pass drug exposure is to the target cell population and the amount of drug available to the systemic circulation may be greatly reduced. We hypothesize that this approach to retinoid delivery will result in a significantly greater therapeutic index. Direct delivery of the drug to epithelial surfaces afflicted by early cancer may also be a general strategy for improving the therapeutic index with other chemoprevention agents. C1 NCI, Intervent Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, Rockville, MD 20850 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, 9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5778-9 J9 RESP PHARM & PHARMAC PY 1998 BP 273 EP 283 PG 11 WC Oncology; Pharmacology & Pharmacy; Respiratory System SC Oncology; Pharmacology & Pharmacy; Respiratory System GA BK39D UT WOS:000071971200024 ER PT J AU Bartlett, MS Angus, WC Shaw, MM Durant, PJ Lee, CH Pascale, JM Smith, JW AF Bartlett, MS Angus, WC Shaw, MM Durant, PJ Lee, CH Pascale, JM Smith, JW TI Antibody to Pneumocystis carinii protects rats and mice from developing pneumonia SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFECTION; MODELS; HYPOGAMMAGLOBULINEMIA; PROPHYLAXIS; DETERMINANT; EXPRESSION; EFFICACY; IMMUNITY; THERAPY; DRUGS AB Well-proven mouse and rat models were used to show that polyclonal antisera to Pneumocystis carinii protect against P. carinii pneumonia, Antibodies were obtained from animals that were allowed to recover from severe P. carinii pneumonia after immunosuppression had been stopped and which then were given a booster injection of P. carinii from the same animal species. Mice immunosuppressed with corticosteroids or antibodies to L3T4(+) lymphocytes (which are comparable to CD4 cells of humans) and transtracheally inoculated with mouse P. carinii did not develop P, carinii pneumonia if they were passively immunized with antiserum, while mice immunosuppressed and inoculated by identical procedures but not given antibodies developed severe infections, Rats immunosuppressed with corticosteroids and inoculated with rat P, carinii had less severe infections if they were given rat anti-P, carinii antisera, The polyclonal antisera developed in mice provided greater protection for the mice than the polyclonal rat antisera did for the rats; however, the potencies and compositions of the antisera were not quantitated and probably differed, Since both rats and mice can be protected from P, carinii infections with polyclonal antisera, it may be possible to develop vaccines that will elicit protective antibodies in humans. C1 Indiana Univ, Sch Med, Dept Lab Med & Pathol, Indianapolis, IN 46202 USA. NIH, Bethesda, MD 20892 USA. RP Bartlett, MS (reprint author), Indiana Univ, Sch Med, Dept Lab Med & Pathol, MS A-128,635 Barnhill Dr, Indianapolis, IN 46202 USA. NR 30 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 1998 VL 5 IS 1 BP 74 EP 77 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YW073 UT WOS:000071893400015 PM 9455884 ER PT J AU Fitzgerald, D Pastan, I Robertus, J AF Fitzgerald, D Pastan, I Robertus, J TI Clinical applications of immunotoxins - Introduction SO CLINICAL APPLICATIONS OF IMMUNOTOXINS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID PSEUDOMONAS EXOTOXIN-A; CONSERVED FRAMEWORK REGIONS; RECEPTOR-RELATED PROTEIN; GALACTOSE-BINDING SITES; DIPHTHERIA-TOXIN; NUCLEOTIDE-SEQUENCE; CRYSTAL-STRUCTURE; RECOMBINANT IMMUNOTOXINS; ESCHERICHIA-COLI; CATALYTIC DOMAIN C1 NCI, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. RP Fitzgerald, D (reprint author), NCI, Mol Biol Lab, Div Basic Sci, Bldg 37-4E16, Bethesda, MD 20892 USA. NR 53 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 234 BP 1 EP 11 PG 11 WC Immunology; Microbiology SC Immunology; Microbiology GA BM12S UT WOS:000077723000001 PM 9670609 ER PT J AU Engert, A Sausville, EA Vitetta, E AF Engert, A Sausville, EA Vitetta, E TI The emerging role of ricin A-chain immunotoxins in leukemia and lymphoma SO CLINICAL APPLICATIONS OF IMMUNOTOXINS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; DISSEMINATED DAUDI-LYMPHOMA; VASCULAR LEAK SYNDROME; B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-PARENCHYMAL CELLS; THY 1.1 ANTIBODY; PHASE-I TRIAL; MONOCLONAL-ANTIBODIES; CYTO-TOXICITY C1 Univ Cologne, Dept Internal Med 1, D-50924 Cologne, Germany. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75235 USA. RP Engert, A (reprint author), Univ Cologne, Dept Internal Med 1, D-50924 Cologne, Germany. EM a.engert@uni-koeln.de FU NCI NIH HHS [CA28149] NR 112 TC 20 Z9 21 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 234 BP 13 EP 33 PG 21 WC Immunology; Microbiology SC Immunology; Microbiology GA BM12S UT WOS:000077723000002 PM 9670610 ER PT J AU Pai, LH Pastan, I AF Pai, LH Pastan, I TI Clinical trials with Pseudomonas exotoxin immunotoxins SO CLINICAL APPLICATIONS OF IMMUNOTOXINS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID RECOMBINANT FUSION PROTEIN; SINGLE-CHAIN IMMUNOTOXIN; GROWTH-FACTOR RECEPTOR; HUMAN OVARIAN-CANCER; NUDE-MOUSE MODEL; CYTOTOXIC ACTIVITY; MONOCLONAL-ANTIBODY; COMPLETE REGRESSION; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pai, LH (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 39 TC 11 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 234 BP 83 EP 96 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA BM12S UT WOS:000077723000006 PM 9670614 ER PT J AU Oldfield, EH Youle, RJ AF Oldfield, EH Youle, RJ TI Immunotoxins for brain tumor therapy SO CLINICAL APPLICATIONS OF IMMUNOTOXINS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID TRANSFERRIN RECEPTOR; LEPTOMENINGEAL NEOPLASIA; FUSION PROTEINS; SOLID TUMORS; EFFICACY; ANTIBODY; TISSUE; DELIVERY; KINETICS; GLIOMAS C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. NR 41 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 234 BP 97 EP 114 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BM12S UT WOS:000077723000007 PM 9670615 ER PT J AU Dawson, N Figg, WD Brawley, OW Bergan, R Cooper, MR Senderowicz, A Headlee, D Steinberg, SM Sutherland, M Patronas, N Sausville, E Linehan, WM Reed, E Sartor, O AF Dawson, N Figg, WD Brawley, OW Bergan, R Cooper, MR Senderowicz, A Headlee, D Steinberg, SM Sutherland, M Patronas, N Sausville, E Linehan, WM Reed, E Sartor, O TI Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: Simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal SO CLINICAL CANCER RESEARCH LA English DT Article ID PALLIATIVE END-POINTS; FLUTAMIDE WITHDRAWAL; ADAPTIVE-CONTROL; RECEPTOR GENE; ORAL ETOPOSIDE; CARCINOMA; ANTIGEN; TRIAL; TOXICITY; MUTATION AB Management of prostate cancer progression after failure of initial hormonal therapy is controversial, Recently, the activity of the simple discontinuation of antiandrogen therapy has been established by several groups, as well as the enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide and hydrocortisone), Furthermore, suramin has generated considerable interest following reports of response rates ranging from 17 to 70%, More recently, suramin response rates of 18 and 22% have been reported when the potential confounding variables of flutamide withdrawal and hydrocortisone were prospectively controlled, On the basis of the activity of combining aminoglutethimide with flutamide withdrawal, we designed a protocol in which suramin was combined with aminoglutethimide in two cohorts of patients (those with simultaneous antiandrogen withdrawal compared to those who had previously discontinued antiandrogen therapy), Eighty-one evaluable patients were enrolled in th:is study between June 1992 and November 1994, Patients were a priori divided into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the patients were enrolled into the trial, For the group that discontinued antiandrogen prior to enrolling in therapy, the partial response rate (>50% decline in PSA for >4 weeks) was 14.2%, whereas the partial response was 44% for those patients who discontinued their antiandrogen at the time of starting suramin and aminoglutethimide, The median time to progression was 3.9 months in patients failing prior antiandrogen withdrawal and 5.5 months in those patients having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference), The progression-free survival estimate at 1 year for patients having prior antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%], For those patients who experienced antiandrogen withdrawal simultaneous with the treatment, the progression-free survival estimates:it 1 and 2 years were 27.1 (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%), The median survival time for those patients having prior antiandrogen withdrawal was 14.2 months, whereas the median survival was 21.9 months for those having concomitant antiandrogen withdrawal (P = 0.029 for the overall difference). In conclusion, the partial response rate of 44% for those who had concomitant flutamide withdrawal with adrenal suppression was consistent with that of other reports using a similar maneuver, Although this study was not randomized and thus we should not over-interpret the results, flutamide withdrawal plus adrenal suppression appears to have greater activity than flutamide withdrawal alone, Furthermore, these data suggest that suramin adds little to the response rate observed for other adrenal suppressive agents in the presence of antiandrogen withdrawal, This interpretation is in agreement with those studies controlling for adrenal suppression and flutamide withdrawal prior to suramin administration, which noted modest activity of short duration, Given that antiandrogen withdrawal is now accepted as an active maneuver for a subset of patients progressing after maximum androgen blockade, we propose that future trials attempting to maximize response rates incorporate this maneuver whenever possible into prospectively designed regimens. C1 NCI, Clin Pharmacol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Branch, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 65 TC 30 Z9 30 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 JAN PY 1998 VL 4 IS 1 BP 37 EP 44 PG 8 WC Oncology SC Oncology GA YT599 UT WOS:000071623200006 PM 9516950 ER PT J AU Khumalo, H Gomo, ZAR Moyo, VM Gordeuk, VR Saungweme, T Rouault, TA Gangaidzo, IT AF Khumalo, H Gomo, ZAR Moyo, VM Gordeuk, VR Saungweme, T Rouault, TA Gangaidzo, IT TI Serum transferrin receptors are decreased in the presence of iron overload SO CLINICAL CHEMISTRY LA English DT Article ID ELEMENT BINDING-PROTEIN; FERRITIN MESSENGER-RNA; RESPONSIVE ELEMENT; HEREDITARY HEMOCHROMATOSIS; SULFUR CLUSTER; METABOLISM; CELLS; LIVER AB To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r greater than or equal to 0.44; P <0.001). The mean +/- SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin >300 mu g/L and transferrin saturation >60%) was 1.55 +/- 0.61 mg/L, significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20-300 mu g/L and transferrin saturation 15-55%; P <0.0005) and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin <20 mu g/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Dept Med, Harare, Zimbabwe. Univ Zimbabwe, Sch Med, Dept Chem Pathol, Harare, Zimbabwe. George Washington Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Washington, DC 20037 USA. RP Gomo, ZAR (reprint author), NICHHD, Cell Biol & Metab Branch, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [1-HD3-3196] NR 41 TC 55 Z9 59 U1 0 U2 2 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 JAN PY 1998 VL 44 IS 1 BP 40 EP 44 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YQ903 UT WOS:000071436000006 PM 9550556 ER PT J AU Molloy, AM Mills, JL Kirke, PN Whitehead, AS Weir, DG Scott, JM AF Molloy, AM Mills, JL Kirke, PN Whitehead, AS Weir, DG Scott, JM TI Whole-blood folate values in subjects with different methylenetetrahydrofolate reductase genotypes: Differences between the radioassay and microbiological assays SO CLINICAL CHEMISTRY LA English DT Letter ID RISK FACTOR C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. Hlth Res Board, Dublin, Ireland. NICHHD, Bethesda, MD 20892 USA. RP Scott, JM (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NR 11 TC 50 Z9 51 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 JAN PY 1998 VL 44 IS 1 BP 186 EP 188 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YQ903 UT WOS:000071436000031 PM 9550581 ER PT J AU Cannon, RO AF Cannon, RO TI Role of nitric oxide in cardiovascular disease: focus on the endothelium SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 21st Annual Arnold O Beckman Conference in Clinical Chemistry CY JAN 25-26, 1998 CL SAN FRANCISCO, CA ID CORONARY-ARTERY DISEASE; DEPENDENT VASCULAR RELAXATION; CHOLESTEROL-LOWERING THERAPY; LOW-DENSITY-LIPOPROTEIN; L-ARGININE; ESSENTIAL-HYPERTENSION; VASOMOTOR RESPONSE; HYPERCHOLESTEROLEMIC PATIENTS; RELAXING FACTOR; RISK-FACTORS AB Nitric oxide is a soluble gas continuously synthesized by the endothelium. This substance has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood. A growing list of conditions, including those commonly associated as risk factors for atherosclerosis Such as hypertension and hypercholesterolemia, are associated with diminished release of nitric oxide into the arterial wall either because of impaired synthesis or excessive oxidative degradation. Diminished nitric oxide bioactivity may cause constriction of coronary arteries during exercise or during mental stress and contribute to provocation of myocardial ischemia in patients with coronary artery disease. Additionally, diminished nitric oxide bioactivity may facilitate vascular inflammation that could lead to oxidation of lipoproteins and foam cell formation, the precursor of the atherosclerotic plaque. Numerous therapies have been investigated to assess the possibility of reversing endothelial dysfunction by enhancing the release of nitric oxide from the endothelium, either through stimulation of nitric oxide synthesis or protection of nitric oxide from oxidative inactivation and conversion to toxic molecules such as peroxynitrite. Accordingly, causal relationships between improved endothelial function and reduction in myocardial ischemia and acute coronary events can now be investigated. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. EM cannonr@gwgate.nhlbi.nih.gov NR 91 TC 177 Z9 186 U1 2 U2 11 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. PY 1998 VL 44 IS 8 SI SI BP 1809 EP 1819 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 108XZ UT WOS:000075292900003 PM 9702990 ER PT J AU Seftor, REB Seftor, EA De Larco, JE Kleiner, DE Leferson, J Stetler-Stevenson, WG McNamara, TF Golub, LM Hendrix, MJC AF Seftor, REB Seftor, EA De Larco, JE Kleiner, DE Leferson, J Stetler-Stevenson, WG McNamara, TF Golub, LM Hendrix, MJC TI Chemically modified tetracyclines inhibit human melanoma cell invasion and metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE chemically modified tetracyclines; invasion; matrix metalloproteinases; melanoma; metastasis ID MATRIX METALLOPROTEINASES; TUMOR PROGRESSION; IV COLLAGENASE; NONANTIMICROBIAL TETRACYCLINE; DOMAIN-STRUCTURE; ACTIVATION; MEMBRANE; CANCER; PROCOLLAGENASE; DOXYCYCLINE AB Recent work has shown that chemically modified tetracyclines (CMTs) are potent inhibitors of matrix metalloproteinase (MMP) activity, both in vitro and in vivo, which is distinct from their antimicrobial activities (Golub et al, Crit Rev Oral Biol Med, 2, 297-321, 1991; Ryan et al, Curr Opin Rheumatol, 8, 238-47, 1996), The process of tumor cell invasion requires MMP-mediated degradation of extracellular matrix barriers as a key step in the metastasic cascade. In this study, we examined the effect(s) of doxycycline and CMTs on estracellular levels of gelatinase A and B activity from a highly invasive and metastatic human melanoma cell line C8161, and correlated these observations with changes in the cells' biological behavior in an in vitro invasion assay and in an in vivo SCID mouse model, The results indicate that coincident with the ability of these compounds to differentially suppress extracellular levels of gelatinase activity, C8161 cells treated with doxycycline, CMT-1, CMT-3, or CMT-6 were less invasive in vitro in a dose-dependent manner (3-50 mu g/ml). Furthermore, data derived from the in vivo model indicate that SCID mice dosed orally with CMT-1 or CMT-3 contained a reduced number of lung metastases following i.v. injection of C8161 cells via tail vein inoculation. These observations suggest that careful screening of different CMTs could lead to the identification of compounds which suppress the formation and magnitude of metastases associated with certain cancers, and if used as an adjunct to other treatment regimes, lead to greater efficacy in the treatment of metastatic cancers. (C) 1998 Lippincott-Raven Publishers. C1 Univ Iowa, Dept Anat & Cell Biol, Iowa Canc Ctr, Coll Med, Iowa City, IA 52242 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NCI, Pathol Lab, Extracellular Matrix Pathol Sect, Bethesda, MD 20892 USA. SUNY Stony Brook, Sch Dent Med, Dept Oral Biol & Pathol, Stony Brook, NY 11794 USA. RP Seftor, REB (reprint author), Univ Iowa, Dept Anat & Cell Biol, Iowa Canc Ctr, Coll Med, 51 Newton Rd,1-100 BSB, Iowa City, IA 52242 USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 FU NIDCR NIH HHS [DE03987] NR 28 TC 119 Z9 120 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 1998 VL 16 IS 3 BP 217 EP 225 DI 10.1023/A:1006588708131 PG 9 WC Oncology SC Oncology GA ZF952 UT WOS:000072949700002 PM 9568639 ER PT J AU Biesecker, LG AF Biesecker, LG TI Lumping and splitting: molecular biology in the genetics clinic SO CLINICAL GENETICS LA English DT Review ID PALLISTER-HALL SYNDROME; CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; IMPERFORATE ANUS; HYPOPITUITARISM C1 NHGRI, NIH, Lab Genet Dis Res, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, Lab Genet Dis Res, Bldg 49 Room 4A80, Bethesda, MD 20892 USA. NR 22 TC 24 Z9 25 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 1998 VL 53 IS 1 BP 3 EP 7 DI 10.1034/j.1399-0004.1998.531530102.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZA074 UT WOS:000072326300002 PM 9550355 ER PT J AU Dworkin, MS Anderson, DE Schwan, TG Shoemaker, PC Banerjee, SN Kassen, BO Burgdorfer, W AF Dworkin, MS Anderson, DE Schwan, TG Shoemaker, PC Banerjee, SN Kassen, BO Burgdorfer, W TI Tick-borne relapsing fever in the northwestern United States and southwestern Canada SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BORRELIA-HERMSII; LYME-DISEASE; SEROLOGICAL DISCRIMINATION; ANTIGENIC VARIATION; PROTEINS; IDENTIFICATION; CULTIVATION AB Records from 182 cases of tick-borne relapsing fever (TBRF) were reviewed. In confirmed cases, there was febrile illness, and spirochetes were identified on peripheral blood preparations, In probable cases, there were clinical features of TBRF and either the same exposure as a confirmed case or serological (indirect fluorescent antibody test and western blotting [WB]) evidence of infection with Borrelia hermsii. Sera also were tested for antibody to Borrelia burgdorferi. We identified 133 confirmed and 49 probable cases of TBRF. A jarisch-Herxheimer reaction was reported in 33 (54.1%) of 61 cases for which this information was available. Most patients who had antibodies to B. hermsii were serologically positive for B. burgdorferi, and WE demonstrated false positivity of testing for B. burgdorferi Thirty-five(21%) of 166 cases were unreported to public health authorities. In 52 cases, there were more than two relapses before the diagnosis. This study demonstrates that TBRF is underrecognized and underreported and map be falsely identified as Lyme disease. C1 Sacred Heart Med Ctr, Dept Lab Med, Spokane, WA 99220 USA. Washington State Dept Hlth, Sect Communicable Dis Epidemiol, Seattle, WA USA. Washington State Dept Hlth, Epidem Intelligence Serv, Seattle, WA USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA USA. NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. British Columbia Ctr Dis Control, Vector Borne Dis Lab, Vancouver, BC, Canada. Univ British Columbia, British Columbia Ctr Dis Control, Vector Borne Dis Lab, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. RP Anderson, DE (reprint author), Sacred Heart Med Ctr, Dept Lab Med, W 101 8th Ave,TAF-C9, Spokane, WA 99220 USA. NR 45 TC 69 Z9 72 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1998 VL 26 IS 1 BP 122 EP 131 DI 10.1086/516273 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YR235 UT WOS:000071474500020 PM 9455520 ER PT J AU Bunnell, BA Morgan, RA AF Bunnell, BA Morgan, RA TI Gene therapy for infectious diseases SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX VIRUS; HUMAN T-CELLS; HUMAN PAPILLOMAVIRUS TYPE-18; RECOMBINANT SOLUBLE CD4; ALLOGENEIC BONE-MARROW; INHIBITS HIV-1 REPLICATION; SINGLE-CHAIN ANTIBODY; REV ACTIVATION DOMAIN; EXPRESS ANTISENSE RNA AB Gene therapy is being investigated as an alternative treatment for a wide range of infectious diseases that are not amenable to standard clinical management. Approaches to gene therapy for infectious diseases can be divided into thr ee broad categories: (i) gene therapies based on nucleic acid moieties, including antisense DNA or RNA, RNA decoys, and catalytic RNA moieties (ribozymes); (ii) protein approaches such as transdominant negative proteins and single-chain antibodies; and (iii) immunotherapeutic approaches involving generic vaccines or. pathogen-specific lymphocytes. It is further possible that combinations of the afore mentioned approaches will be used simultaneously to inhibit multiple stages of the life cycle of the infectious agent. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rmorgan@nhgri.nih.gov NR 166 TC 57 Z9 60 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JAN PY 1998 VL 11 IS 1 BP 42 EP + PG 16 WC Microbiology SC Microbiology GA YT830 UT WOS:000071649300003 PM 9457428 ER PT J AU Cole, AE AF Cole, AE TI Workshop report on the NIGMS-supported postdoctoral training programs in clinical pharmacology SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID UNITED-STATES C1 Natl Inst Gen Med Sci, Div Pharmacol Physiol & Biol Chem, NIH, Bethesda, MD 20892 USA. RP Cole, AE (reprint author), Natl Inst Gen Med Sci, Div Pharmacol Physiol & Biol Chem, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 1998 VL 63 IS 1 BP 4 EP 10 DI 10.1016/S0009-9236(98)90116-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YV495 UT WOS:000071830800002 PM 9465837 ER EF